Clinical Trials /

Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042

NCT03307785

Description:

Part A: To test the safety and tolerability of combination therapy with Niraparib and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part B: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part C: To test the safety and tolerability of combination therapy with Niraparib, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study. Part D: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study. Part E: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part F: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part G: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part H: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part I: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Related Conditions:
  • Cancer
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042
  • Official Title: Phase 1b Dose-Finding Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042 in Patients With Advanced or Metastatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 213351
  • SECONDARY ID: 3000-01-002
  • NCT ID: NCT03307785

Conditions

  • Neoplasms
  • Metastatic Cancer
  • Advanced Cancer
  • Solid Tumor
  • Non Small Cell Lung Cancer Metastatic
  • Non Small Cell Lung Cancer Stage IIIB
  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
NiraparibZejulaPart A: TSR-042 and niraparib 200 mg QD
TSR-042Part A: TSR-042 and niraparib 200 mg QD
Carboplatin-PaclitaxelPart B: TSR-042 and carboplatin-paclitaxel
BevacizumabAvastinPart C: TSR-042, niraparib 200 mg QD and bevacizumab
TSR-022Part F: TSR-042, TSR-022, and carboplatin-pemetrexed
Carboplatin-PemetrexedPart E: TSR-042 and carboplatin-pemetrexed
Carboplatin-Nab-PaclitaxelPart G: TSR-042 and carboplatin-nab-paclitaxel

Purpose

Part A: To test the safety and tolerability of combination therapy with Niraparib and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part B: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part C: To test the safety and tolerability of combination therapy with Niraparib, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study. Part D: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study. Part E: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part F: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part G: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part H: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study. Part I: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.

Trial Arms

NameTypeDescriptionInterventions
Part A: TSR-042 and niraparib 200 mg QDExperimentalPatients will receive TSR-042 500 milligram (mg), intravenous (IV) infusion on Day 1 of every cycle (every 3 weeks [Q3W]) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (every 6 weeks [Q6W]) beginning on Day 1 of Cycle 5 along with niraparib 200 mg, once daily (QD), orally on Days 1 to 21 repeated Q3W.
  • Niraparib
  • TSR-042
Part A: TSR-042 and niraparib 300 mg QDExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg, QD, orally on Days 1 to 21 repeated Q3W.
  • Niraparib
  • TSR-042
Part B: TSR-042 and carboplatin-paclitaxelExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 milligram per square meter (mg/m^2), IV infusion on Day 1 Q3W administered for 4 to 6 cycles.
  • TSR-042
  • Carboplatin-Paclitaxel
Part C: TSR-042, niraparib 200 mg QD and bevacizumabExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 200 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kilogram (kg), IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
  • Niraparib
  • TSR-042
  • Bevacizumab
Part C: TSR-042, niraparib 300 mg QD and bevacizumabExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
  • Niraparib
  • TSR-042
  • Bevacizumab
Part D: TSR-042, carboplatin-paclitaxel and bevacizumabExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W administered for 4 to 6 cycles; and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
  • TSR-042
  • Carboplatin-Paclitaxel
  • Bevacizumab
Part E: TSR-042 and carboplatin-pemetrexedExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation) administered for 6 cycles (each cycle is 21 days).
  • TSR-042
  • Carboplatin-Pemetrexed
Part F: TSR-042, TSR-022, and carboplatin-pemetrexedExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); and TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W administered for 5 cycles (each cycle is 21 days); and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation).
  • TSR-042
  • TSR-022
  • Carboplatin-Pemetrexed
Part G: TSR-042 and carboplatin-nab-paclitaxelExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (every week [Q1W]) of every 3 week cycle for 4 to 6 cycles.
  • TSR-042
  • Carboplatin-Nab-Paclitaxel
Part H: TSR-042, TSR-022, and carboplatin-nab-paclitaxelExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (Q1W) of every 3 week cycle for 4 to 6 cycles.
  • TSR-042
  • TSR-022
  • Carboplatin-Nab-Paclitaxel
Part I: TSR-042, TSR-022, and carboplatin-paclitaxelExperimentalPatients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days).
  • TSR-042
  • Carboplatin-Paclitaxel
  • TSR-022

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has histologically or cytologically proven advanced (unresectable) or
             metastatic cancer as outlined below according to study part and disease type:

          -  Part A: Patients with previously treated advanced or metastatic cancer. Patient may
             have received no more than 4 lines of treatment for advanced or metastatic cancer.
             Hormonal treatment will not be considered a prior line of treatment.

          -  Part B: Patients with advanced or metastatic cancer for which treatment with
             carboplatin-paclitaxel is considered appropriate therapy. Patient may have received no
             more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment
             will not be considered a prior line of treatment.

          -  Part C: Patients with previously treated advanced or metastatic cancer. Patient may
             have received no more than 4 lines of treatment for advanced or metastatic cancer.
             Hormonal treatment will not be considered a prior line of treatment.

          -  Part D: Patients in whom carboplatin-paclitaxel and bevacizumab is considered
             appropriate therapy. Patient may have received no more than 1 prior line of
             chemotherapy in the metastatic setting. Hormonal treatment will not be considered a
             prior line of treatment.

          -  Part E and F: Patients who have not received prior systemic therapy, including
             targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB
             or IV) Non-Squamous NSCLC. Patients who have received neoadjuvant or adjuvant therapy
             are eligible as long as development of advanced or metastatic disease occurred at
             least 12 months after completion of neoadjuvant or adjuvant therapy.

          -  Part G, H, and I: Patients who have not received prior systemic therapy, including
             targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB
             or IV) NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible
             as long as development of advanced or metastatic disease occurred at least 12 months
             after completion of neoadjuvant or adjuvant therapy.

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          -  Patient has adequate organ function.

          -  Female patient has a negative serum pregnancy test within 72 hours prior to taking
             study treatment if of childbearing potential and agrees to abstain from activities
             that could result in pregnancy from screening through 180 days after the last dose of
             study treatment, or is of non-childbearing potential.

          -  Male patient agrees to use an adequate method of contraception and not donate sperm
             starting with the first dose of study treatment through 90 days after the last dose of
             study treatment. Note: Abstinence is acceptable if this is the established and
             preferred contraception for the patient.

          -  Patient has measurable lesions by RECIST v1.1.

        For Part A and C, in addition to the general inclusion criteria, patients must also meet
        the following additional criterion to be considered eligible to participate in this study:

          -  Patient is able to take oral medications.

          -  For patients to be eligible for any parts of the study using niraparib 300 mg as a
             starting dose, a screening actual body weight ≥ 77 kg and screening platelet count ≥
             150,000 u/L is necessary.

        Exclusion Criteria: (Patients will not be eligible for the study entry if any of the
        following criteria are met)

          -  Patient has known active central nervous system metastases, carcinomatous meningitis,
             or both.

          -  Patient has a known additional malignancy that progressed or required active treatment
             within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous
             cell carcinoma of the skin that has undergone potentially curative therapy, or in situ
             cervical cancer.

          -  Patient is considered a poor medical risk due to a serious, uncontrolled medical
             disorder, nonmalignant systemic disease, or active infection that requires systemic
             therapy.

          -  Patient has a condition (such as transfusion-dependent anemia or thrombocytopenia),
             therapy, or laboratory abnormality that might confound the study results or interfere
             with the patient's participation

          -  Patient is pregnant or expecting to conceive children within the projected duration of
             the study, starting with the screening visit through 180 days after the last dose of
             study treatment.

        Note: No data are available regarding the presence of niraparib or its metabolites in human
        milk, or on its effects on the breastfed infant or milk production. Because of the
        potential for serious adverse reactions in breastfed infants from niraparib, female
        patients should not breastfeed during treatment with niraparib and for 1 month after
        receiving the final dose.

          -  Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies).

          -  Patient has known active hepatitis B or hepatitis C.

          -  Patient has an active autoimmune disease that has required systemic treatment in the
             past 2 years.

          -  Patient has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2,
             anti-CTLA-4 including ipilimumab), or any other antibody or drug specifically
             targeting T-cell co-stimulation or checkpoint pathways.

          -  Patient has undergone prior treatment with a known PARP inhibitor.

          -  Known history or current diagnosis of MDS or AML.

          -  Patient has a known hypersensitivity to TSR-042 components or excipients.

        For Parts B, D, E, F, G, H, and I, patients will not be eligible for study entry if any of
        the following additional exclusion criterion are met:

        • Patient has a known hypersensitivity to any of the following relevant study treatments:
        carboplatin, paclitaxel, pemetrexed, nab-paclitaxel, or TSR-022 components or excipients.

        For Parts C and D only, patients will not be eligible for study entry if the following
        additional exclusion criterion is met:

          -  Patient has clinically significant cardiovascular disease (e.g., significant cardiac
             conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac
             arrhythmia or unstable angina, New York Heart Association Grade 2 or greater
             congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or
             greater peripheral vascular disease, and history of cerebrovascular accident [CVA])
             within 6 months of enrollment.

          -  Patient has a history of bowel obstruction, including subocclusive disease, related to
             the underlying disease and history of abdominal fistula, gastrointestinal perforation,
             or intra abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic
             examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.

          -  Patient has proteinuria as demonstrated by urine protein: creatinine ratio ≥1.0 at
             screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2
             proteinuria on dipstick at baseline should undergo 24-hour urine collection and must
             demonstrate <2 g of protein in 24 hours to be eligible).

          -  Patient is at increased bleeding risk due to concurrent conditions (e.g., major
             injuries or surgery within the past 28 days prior to start of study treatment, history
             of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or
             clinically significant hemorrhage within the past 3 months).

          -  Patient has a known hypersensitivity to bevacizumab components or excipients.

        For Parts E and F only, patients will not be eligible for study entry if any of the
        following additional exclusion criteria are met:

          -  Patient is unable to interrupt aspirin or other nonsteroidal ant-inflammatory drugs,
             other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long
             -acting agents, such as piroxicam.

          -  Patient is unable or unwilling to take folic acid, vitamin B12 supplement.

          -  Patient has symptomatic ascites or pleural effusion. A patient who is clinically
             stable following treatment for these conditions (including therapeutic thoraco- or
             paracentesis) is eligible.

        For Parts G, H, and I only, patients will not be eligible for study entry if any of the
        following additional exclusion criteria are met:

        • Patient has pre-existing peripheral neuropathy that is Grade ≥ 2 by Common Terminology
        Criteria for Adverse Events (CTCAE) version 4 criteria.

        For Parts E, F, G, H and I only, patients will not be eligible for study entry if any of
        the following additional exclusion criteria are met:

        • Patient has interstitial lung disease or a history of pneumonitis that required oral or
        intravenous glucocorticoids to assist with management.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Number of Participants With Dose-limiting Toxicity (DLT)
Time Frame:21 days
Safety Issue:
Description:An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of adverse event(AE) onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish recommended phase 2 dose (RP2D).

Secondary Outcome Measures

Measure:Part A: Objective Response Rate
Time Frame:Up to 28.5 months
Safety Issue:
Description:Objective Response Rate is defined as the percentage of participants who achieved confirmed complete response (CR) or partial response (PR), evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis. PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part B: Objective Response Rate
Time Frame:Up to 28.5 months
Safety Issue:
Description:Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part C: Objective Response Rate
Time Frame:Up to 22.5 months
Safety Issue:
Description:Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part D: Objective Response Rate
Time Frame:Up to 9.5 months
Safety Issue:
Description:Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part E: Objective Response Rate
Time Frame:Up to 4.4 months
Safety Issue:
Description:Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part F: Objective Response Rate
Time Frame:Up to 3.5 months
Safety Issue:
Description:Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part G: Objective Response Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part H: Objective Response Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part I: Objective Response Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Measure:Part A: Duration of Response
Time Frame:Up to 28.5 months
Safety Issue:
Description:Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Measure:Part B: Duration of Response
Time Frame:Up to 28.5 months
Safety Issue:
Description:Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. Data is not reported as participants response is still ongoing at the time of primary analysis.
Measure:Part C: Duration of Response
Time Frame:Up to 22.5 months
Safety Issue:
Description:Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. Data is not reported as participants response is still ongoing at the time of primary analysis.
Measure:Part D: Duration of Response
Time Frame:Up to 9.5 months
Safety Issue:
Description:Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. Data is not reported as participants response is still ongoing at the time of primary analysis.
Measure:Part E: Duration of Response
Time Frame:Up to 4.4 months
Safety Issue:
Description:Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Measure:Part F: Duration of Response
Time Frame:Up to 3.5 months
Safety Issue:
Description:Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Measure:Part G: Duration of Response
Time Frame:Up to 24 months
Safety Issue:
Description:Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Measure:Part H: Duration of Response
Time Frame:Up to 24 months
Safety Issue:
Description:Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Measure:Part I: Duration of Response
Time Frame:Up to 24 months
Safety Issue:
Description:Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Measure:Part A: Disease Control Rate
Time Frame:Up to 28.5 months
Safety Issue:
Description:Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or stable disease (SD) per RECIST version 1.1.
Measure:Part B: Disease Control Rate
Time Frame:Up to 28.5 months
Safety Issue:
Description:Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Measure:Part C: Disease Control Rate
Time Frame:Up to 22.5 months
Safety Issue:
Description:Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Measure:Part D: Disease Control Rate
Time Frame:Up to 9.5 months
Safety Issue:
Description:Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Measure:Part E: Disease Control Rate
Time Frame:Up to 4.4 months
Safety Issue:
Description:Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Measure:Part F: Disease Control Rate
Time Frame:Up to 3.5 months
Safety Issue:
Description:Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Measure:Part G: Disease Control Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Measure:Part H: Disease Control Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Measure:Part I: Disease Control Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Measure:Part A: Progression-free Survival
Time Frame:Up to 28.5 months
Safety Issue:
Description:Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Measure:Part B: Progression-free Survival
Time Frame:Up to 28.5 months
Safety Issue:
Description:Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Measure:Part C: Progression-free Survival
Time Frame:Up to 22.5 months
Safety Issue:
Description:Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Measure:Part D: Progression-free Survival
Time Frame:Up to 9.5 months
Safety Issue:
Description:Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Measure:Part E: Progression-free Survival
Time Frame:Up to 4.4 months
Safety Issue:
Description:Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Measure:Part F: Progression-free Survival
Time Frame:Up to 3.5 months
Safety Issue:
Description:Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Measure:Part G: Progression-free Survival
Time Frame:Up to 24 months
Safety Issue:
Description:Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.
Measure:Part H: Progression-free Survival
Time Frame:Up to 24 months
Safety Issue:
Description:Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.
Measure:Part I: Progression-free Survival
Time Frame:Up to 24 months
Safety Issue:
Description:Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.
Measure:Part A: Number of Participants With Positive Anti-TSR-042 Antibodies
Time Frame:Up to 28.5 months
Safety Issue:
Description:Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). Anti-drug Antibody Population consisted of all participants who received at least 1 dose of study treatment and had provided a pre-dose blood sample and at least 1 post-dose blood sample at or after 96 hours.
Measure:Part B: Number of Participants With Positive Anti-TSR-042 Antibodies
Time Frame:Up to 28.5 months
Safety Issue:
Description:Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part C: Number of Participants With Positive Anti-TSR-042 Antibodies
Time Frame:Up to 22.5 months
Safety Issue:
Description:Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part D: Number of Participants With Positive Anti-TSR-042 Antibodies
Time Frame:Up to 9.5 months
Safety Issue:
Description:Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part E: Number of Participants With Positive Anti-TSR-042 Antibodies
Time Frame:Up to 4.4 months
Safety Issue:
Description:Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part F: Number of Participants With Positive Anti-TSR-042 Antibodies
Time Frame:Up to 3.5 months
Safety Issue:
Description:Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part F: Number of Participants With Positive Anti-TSR-022 Antibodies
Time Frame:Up to 3.5 months
Safety Issue:
Description:Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part G: Number of Participants With Positive Anti-TSR-042 Antibodies
Time Frame:Up to 24 months
Safety Issue:
Description:Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planeed to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part H: Number of Participants With Positive Anti-TSR-042 Antibodies
Time Frame:Up to 24 months
Safety Issue:
Description:Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part H: Number of Participants With Positive Anti-TSR-022 Antibodies
Time Frame:Up to 24 months
Safety Issue:
Description:Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part I: Number of Participants With Positive Anti-TSR-042 Antibodies
Time Frame:Up to 24 months
Safety Issue:
Description:Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part I: Number of Participants With Positive Anti-TSR-022 Antibodies
Time Frame:Up to 24 months
Safety Issue:
Description:Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Measure:Part A: Area Under the Plasma Concentration From Time Zero to t (AUC[0-t]) of Niraparib
Time Frame:Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. Pharmacokinetic (PK) parameters of niraparib were calculated using non-compartmental methods. PK population consisted of all participants who received at least 1 dose of study treatment and had at least 1 PK sample.
Measure:Part A: AUC(0-t) of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: AUC0-t of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: AUC0-t of Niraparib
Time Frame:Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: AUC0-t of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: AUC0-t of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: AUC0-t of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: AUC0-t of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: AUC0-t of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: AUC0-t of TSR-042
Time Frame:Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: AUC0-t of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: AUC0-t of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: AUC0-t of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: AUC0-t of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Area Under the Plasma Concentration From Time Zero to Infinity (AUC[0-infinity]) of Niraparib
Time Frame:Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: AUC(0-infinity) of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: AUC(0-infinity) of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: AUC(0-infinity) of Niraparib
Time Frame:Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: AUC(0-infinity) of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: AUC(0-infinity) of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: AUC(0-infinity) of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: AUC(0-infinity) of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: AUC(0-infinity) of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: AUC(0-infinity) of TSR-042
Time Frame:Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: AUC(0-infinity) of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: AUC(0-infinity) of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: AUC(0-infinity) of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: AUC(0-infinity) of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Observed Concentration at the End of the Dosing Interval (Ctau) of Niraparib
Time Frame:Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: Ctau of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: Ctau of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: Ctau of Niraparib
Time Frame:Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: Ctau of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: Ctau of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: Ctau of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Ctau of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Ctau of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: Ctau of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Ctau of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Ctau of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Ctau of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Ctau of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Maximum Observed Plasma (Cmax) of Niraparib
Time Frame:Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: Cmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: Cmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: Cmax of Niraparib
Time Frame:Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: Cmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: Cmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: Cmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Cmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Cmax of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: Cmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Cmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Cmax of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Cmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Cmax of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Clearance After Oral Administration (CL/F) of Niraparib
Time Frame:Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: Clearance After Intravenous Administration (CL) of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: CL of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: CL/F of Niraparib
Time Frame:Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: CL of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: CL of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: CL of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: CL of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: CL of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: CL of TSR-042
Time Frame:Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: CL of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: CL of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: CL of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: CL of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Volume of Distribution After Oral Administration (Vz/F) of Niraparib
Time Frame:Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: Volume of Distribution After Intravenous Administration (Vz) of of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: Vz of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: Vz/F of Niraparib
Time Frame:Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: Vz of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: Vz of TSR-042
Time Frame:Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: Vz of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Vz of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Vz of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: Vz of TSR-042
Time Frame:Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Vz of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Vz of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Vz of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Vz of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: AUC at Steady State (AUCss) of Niraparib
Time Frame:Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: AUCss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: AUCss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: AUCss of Niraparib
Time Frame:Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: AUCss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: AUCss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: AUCss of TSR-042
Time Frame:Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: AUCss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: AUCss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: AUCss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: AUCss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: AUCss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: AUCss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: AUCss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Ctau at Steady State (Ctau,ss) of Niraparib
Time Frame:Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: Ctau,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: Ctau,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: Ctau,ss of Niraparib
Time Frame:Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: Ctau,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: Ctau,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: Ctau,ss of TSR-042
Time Frame:Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Ctau,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Ctau,ss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: Ctau,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Ctau,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Ctau,ss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Ctau,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Ctau,ss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Cmax at Steady State (Cmax,ss) of Niraparib
Time Frame:Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: Cmax,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: Cmax,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: Cmax,ss of Niraparib
Time Frame:Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: Cmax,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: Cmax,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: Cmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Cmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Cmax,ss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: Cmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Cmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Cmax,ss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Cmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Cmax,ss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Time to Reach Maximum Plasma Concentration (Tmax) of Niraparib
Time Frame:Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: Tmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: Tmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: Tmax of Niraparib
Time Frame:Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: Tmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: Tmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: Tmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Tmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Tmax of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: Tmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Tmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Tmax of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Tmax of TSR-042
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Tmax of TSR-022
Time Frame:Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Tmax at Steady State (Tmax,ss) of Niraparib
Time Frame:Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part A: Tmax,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: Tmax,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: Tmax,ss of Niraparib
Time Frame:Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Measure:Part C: Tmax,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: Tmax,ss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: Tmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Tmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Tmax,ss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: Tmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Tmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Tmax,ss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Tmax,ss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Tmax,ss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part A: Volume of Distribution After Intravenous Administration (Vss) of of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part B: Vss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part C: Vss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part D: Vss of TSR-042
Time Frame:Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part E: Vss of TSR-042
Time Frame:Cycle 2: Pre-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Vss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Measure:Part F: Vss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Measure:Part G: Vss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Vss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part H: Vss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Vss of TSR-042
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.
Measure:Part I: Vss of TSR-022
Time Frame:Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Safety Issue:
Description:Blood samples were planned to be collected at indicated time points.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Tesaro, Inc.

Last Updated

May 10, 2021