Clinical Trials /

Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Compared to Niraparib Capsule

NCT03329001

Description:

This is a two stage, open label, randomized-sequence, single-crossover Phase 1 study to evaluate the relative bioavailability (BA) and Bioequivalence (BE) of niraparib administered as a tablet formulation compared to the reference capsule formulation currently marketed in the United States. Specifically, a 300 mg niraparib tablet will be compared to 3 niraparib capsules (3 × 100 mg).The Extension Phase of this study is to enable patients enrolled in the study to continue to receive treatment with niraparib tablets if they are tolerating it and, in the Investigator's opinion, may receive benefit.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Compared to Niraparib Capsule
  • Official Title: An Open-Label, Randomized-Sequence, Multicenter, Single-Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Formulation Compared to Niraparib Capsule Formulation in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 3000-01-004
  • NCT ID: NCT03329001

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
NiraparibTablet-Capsule Sequence

Purpose

This is a two stage, open label, randomized-sequence, single-crossover Phase 1 study to evaluate the relative bioavailability (BA) and Bioequivalence (BE) of niraparib administered as a tablet formulation compared to the reference capsule formulation currently marketed in the United States. Specifically, a 300 mg niraparib tablet will be compared to 3 niraparib capsules (3 × 100 mg).The Extension Phase of this study is to enable patients enrolled in the study to continue to receive treatment with niraparib tablets if they are tolerating it and, in the Investigator's opinion, may receive benefit.

Trial Arms

NameTypeDescriptionInterventions
Tablet-Capsule SequenceExperimentalSingle dose Niraparib Tablet (1x300mg) followed by single dose Niraparib Capsule (3x100mg) followed by optional daily dosing extension phase
  • Niraparib
Capsule-Tablet SequenceExperimentalSingle dose Niraparib Capsule (3x100mg) followed by single dose Niraparib Tablet (1x300mg) followed by optional daily dosing extension phase
  • Niraparib

Eligibility Criteria

        Main criteria for inclusion:

        PK Phase:

        To be considered eligible to participate in this study, all of the following requirements
        must be met:

          -  Patients with histologically or cytologically confirmed diagnosis of metastatic or
             locally advanced solid tumors that have failed to respond to standard therapy, has
             progressed despite standard therapy, or for which no standard therapy exists, and who
             may benefit from treatment with a PARP inhibitor as assessed by the Investigator.

          -  ECOG performance status of 0 to 2.

          -  Adequate organ function as defined below:

               -  Absolute neutrophil count ≥ 1,500/μL

               -  Platelets ≥ 100,000/μL

               -  Hemoglobin ≥ 9 g/dL (5.6 mM)

               -  Serum creatinine ≤ 1.5 × the upper limit of normal (ULN) or a calculated
                  creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation or 24-hour
                  urine creatinine clearance.

               -  Total bilirubin ≤ 1.5 × ULN except in patients with Gilbert's syndrome. Patients
                  with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct
                  bilirubin.

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
                  unless liver metastases are present, in which case, they must be ≤ 5 × ULN

          -  Patient has recovered to Grade 1 toxicity from prior cancer therapy (a patient with
             Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may
             qualify for this study).

          -  Female Patient of childbearing potential is not breastfeeding, has a negative serum
             pregnancy test within 72 hours prior to taking study drug and agrees to abstain from
             activities that could result in pregnancy from Screening through 180 days after the
             last dose of study drug,

          -  Male patient agrees to use an adequate method of contraception and not donate sperm
             starting with the first dose of study drug through 90 days after the last dose of
             study drug

        Key Exclusion, PK Phase:

          -  Known diagnosis of immunodeficiency

          -  Symptomatic uncontrolled brain or leptomeningeal metastases.

          -  Major surgery within 3 weeks of starting the study or patient has not recovered from
             any effects of any major surgery.

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

          -  Known history of myelodysplastic syndrome or acute myeloid leukemia.

          -  Patient is currently receiving a sensitive cytochrome P450 (CYP) 1A2 substrates with a
             narrow therapeutic index (e.g., tizanidine and theophylline) (Does not apply for
             Extension Phase).

          -  Patient is currently taking any of the following P-glycoprotein (P-gp) inhibitors:
             amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan,
             cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole,
             ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor,
             and verapamil (Does not apply for Extension Phase).

          -  Patient taking proton pump inhibitors, antacids, or histamine 2 blockers within 48
             hours prior to study drug administration, and/or within 6 hours after study drug
             administration (Does not apply for Extension Phase).

          -  Patient has gastric, gastro-esophageal or esophageal cancer; patient is unable to
             swallow orally administered medication; or patient has gastrointestinal disorders or
             significant gastrointestinal resection likely to interfere with the absorption of
             niraparib.

          -  Patient has known active hepatic disease

          -  Patient has a past or current history of chronic alcohol use.

          -  Patient has significant pleural effusion or ascites that is expected to require
             drainage during the PK Phase (Does not apply for Extension Phase).

        Key Inclusion, Extension Phase:

          -  ECOG performance status of 0 to 2.

          -  Adequate organ function as defined below

               -  Absolute neutrophil count ≥ 1,500/μL

               -  Platelets ≥ 100,000/μL

               -  Hemoglobin ≥ 9 g/dL (5.6 mM)

               -  Serum creatinine ≤ 1.5 × the ULN or a calculated creatinine clearance ≥ 60 mL/min
                  using the Cockcroft-Gault equation or 24-hour urine creatinine clearance

               -  Total bilirubin ≤ 1.5 × ULN except in patients with Gilbert's syndrome. Patients
                  with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct
                  bilirubin.

               -  AST and ALT ≤ 2.5 × ULN unless liver metastases are present, in which case, they
                  must be ≤5 × ULN

          -  Female patient of childbearing potential is not breastfeeding, has a negative serum
             pregnancy test within 72 hours prior to taking study drug and agrees to abstain from
             activities that could result in pregnancy from Screening through 180 days after the
             last dose of study drug.

          -  Male patient agrees to use an adequate method of contraception and not donate sperm
             starting with the first dose of study drug through 90 days after the last dose of
             study drug.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Conduct PK assessment of bioavailability of Niraparib as assessed by Maximum Concentration (Cmax) of 300 mg niraparib administered as a tablet versus capsule formulation (Stage 1 and Stage 2) .
Time Frame:Approximately 1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:The number of participants with treatment emergent adverse events (TEAEs) according to NCI CTCAE v4.03
Time Frame:Approximately 1 year
Safety Issue:
Description:To evaluate the safety of single dose niraparib when administered as a tablet or capsule formulation in patients with advanced solid tumors To evaluate the safety of continuously dosed niraparib in a tablet form in patients with advanced solid tumors who participate in the extension phase of the study
Measure:Assess treatment related adverse events in patients who are administered a single dose of niraparib as a capsule or tablet when compared to those that are continuosly dosed with the tablet formulation in the extension phase of the study.
Time Frame:Approximately 1 year
Safety Issue:
Description:
Measure:AUC of metabolite of niraparib (M1) when administered as a tablet or capsule formulation in patients with advanced solid tumors
Time Frame:Approximately 1 year
Safety Issue:
Description:
Measure:Cmax of a metabolite of niraparib (M1) when administered as a tablet or capsule formulation in patients with advanced solid tumors
Time Frame:Approximately 1 year
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tesaro, Inc.

Trial Keywords

  • PARP inhibitor
  • niraparib
  • Zejula

Last Updated

September 5, 2019