Clinical Trials /

A Two-part Study to Characterize Drug-Drug Interaction Effects on Steady-State Pharmacokinetics of Oral Tazemetostat

NCT04537715

Description:

This is a phase I, multi-center, open-label, multi-dose, two-part PK and safety study to characterize the DDI potential of oral Tazemetostat.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Two-part Study to Characterize Drug-Drug Interaction Effects on Steady-State Pharmacokinetics of Oral Tazemetostat
  • Official Title: A Phase I, Open-label Multi-dose Two-part Study to Characterize the Effects of a Strong CYP3A4 Inhibitor and a Strong CYP3A4 Inducer on the Steady-State Pharmacokinetics of Tazemetostat (EPZ-6438) in Subjects With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: EZH-108
  • NCT ID: NCT04537715

Conditions

  • All Malignancies
  • Advanced Malignancies
  • Hematologic Malignancy
  • Solid Tumor
  • Follicular Lymphoma (FL)
  • Non-Hodgkin Lymphoma (NHL)
  • Diffuse Large B-Cell Lymphoma (DLBCL)
  • Epithelioid Sarcoma (ES)
  • Synovial Sarcoma
  • Renal Medullary Carcinoma
  • Mesothelioma
  • Rhabdoid Tumor

Interventions

DrugSynonymsArms
TazemetostatEPZ-6438, TazverikPart 1: Tazemetostat and Itraconazole Drug Interaction Cycle 1
ItraconazoleSporanoxPart 1: Tazemetostat and Itraconazole Drug Interaction Cycle 1
RifampinRIF, Rifampicin, Rifadin, RimactanePart 2:Tazemetostat and Rifampin Drug Interaction Cycle 1

Purpose

This is a phase I, multi-center, open-label, multi-dose, two-part PK and safety study to characterize the DDI potential of oral Tazemetostat.

Detailed Description

      This two-part study is designed to characterize the steady-state PK of oral Tazemetostat and
      its metabolite EPZ 6930 when administered as a single and twice daily dose in subjects with
      advanced malignancies while taken alone or in combination with either itraconazole or
      rifampin.

      Part 1: Tazemetostat and Itraconazole Drug Interaction Part 1 of the study will evaluate the
      drug-drug interaction between Tazemetostat and itraconazole in an open-label, fixed
      sequential cross over design. Subjects in Cycle 1 of Part 1 will be treated for 39 days. On
      Days 1, 15 and 36, a single oral dose of 400 mg Tazemetostat will be administered in the
      morning. From Days 3 - 14 and 21 - 35, subjects will receive an oral 400 mg dose of
      Tazemetostat twice daily (12 hours apart). From Days 18 - 38, a single dose of oral 200 mg
      itraconazole will be administered daily in the morning after a meal, co-administered with
      Tazemetostat when necessary. PK blood samples will be collected on Days 1 - 3, 15 - 18, 21 -
      22, and 36 - 39. Sparse PK samples will be collected on Days 25, 28, 31, and 34.

      Part 2: Tazemetostat and Rifampin Drug Interaction Part 2 of the study will evaluate the
      drug-drug interaction between Tazemetostat and rifampin in an open-label, fixed sequential
      cross over design. Subjects in Cycle 1 of Part 2 will be treated for 26 days. On Days 1, 15
      and 24, a single oral dose of 800 mg Tazemetostat will be administered in the morning. From
      Days 3 - 14 and 17 - 23, subjects will receive an oral 800 mg dose of Tazemetostat twice
      daily (12 hours apart). From Days 17 - 25, a single dose of oral 600 mg rifampin will be
      administered daily in the morning one hour before a meal, co-administered with Tazemetostat
      when necessary. PK blood samples will be collected on Days 1 - 3, 15 - 17 and 24 - 26. Sparse
      PK samples will be collected on Days 19 and 21.

      Subjects may discontinue from the study after completion of Cycle 1 or can continue treatment
      (Cycle2+ onwards) with Tazemetostat at the recommended therapeutic dose of 800 mg twice daily
      until Investigator-assessed clinical disease progression per standard practice, unacceptable
      toxicity, withdrawal of consent, or termination of the study by the sponsor. All subjects who
      receive the recommended therapeutic dose of 800 mg Tazemetostat twice daily for 9 Cycles or
      longer, and are eligible to continue receiving Tazemetostat, will transfer to a Rollover
      Study (EZH-501) for monitoring and continued study drug at the Investigator and Medical
      Monitor's discretion.

      For both Parts 1 and 2, safety and tolerability will be assessed throughout the subject's
      participation. Subjects must have an end of study visit after 30 days of the last dose of
      Tazemetostat for safety assessment.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Tazemetostat and Itraconazole Drug Interaction Cycle 1ExperimentalSubjects in Part 1 of the study will receive a single oral 400 mg dose of Tazemetostat on Day 1, 15 and 36. The subjects will receive Tazemetostat (oral 400 mg dose) tablets to be taken twice daily from Day 3 - 14 and Day 21 - 35. In addition, the subjects will receive oral 200 mg itraconazole daily from Day 18 - 38. Subjects may discontinue from the study after completion of Cycle 1 or can continue treatment (Cycle 2+ onwards) until Investigator-assessed clinical progression per standard practice, or unacceptable toxicity, or until another discontinuation criterion is met. For subjects continuing Tazemetostat treatment at the recommended therapeutic dose (oral 800 mg Tazemetostat twice daily [12 hours apart]), Cycle 2 will begin on day 40 (Cycle 2 Day 1) and each subsequent cycle from Cycle 2+ onwards will be of 28-day duration. Safety and tolerability will be assessed throughout the subject's participation.
  • Tazemetostat
  • Itraconazole
Part 2:Tazemetostat and Rifampin Drug Interaction Cycle 1ExperimentalSubjects in Part 2 of the study will receive a single oral 800 mg dose of Tazemetostat on Day 1, 15 and 24. The subjects will receive Tazemetostat (oral 800 mg dose) tablets to be taken twice daily from Day 3 - 14 and Day 17 - 23. In addition, the subjects will receive oral 600 mg rifampin daily from Day 17 - 25. Subjects may discontinue from the study after completion of Cycle 1 or can continue treatment (Cycle 2+ onwards) until Investigator-assessed clinical progression per standard practice, or unacceptable toxicity, or until another discontinuation criterion is met. For subjects continuing Tazemetostat treatment at the recommended therapeutic dose (800 mg Tazemetostat twice daily [12 hours apart]), Cycle 2 will begin on day 27 (Cycle 2 Day 1) and each subsequent cycle from Cycle 2+ onwards will be of 28-day duration. Safety and tolerability will be assessed throughout the subject's participation.
  • Tazemetostat
  • Rifampin

Eligibility Criteria

        INCLUSION CRITERIA:

          1. Male or female ≥ 18 years age at the time of consent.

          2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

          3. Has the ability to understand informed consent, and provide signed written informed
             consent.

          4. Life expectancy of > 3 months.

          5. Histologically and/or cytologically confirmed advanced metastatic or unresectable
             solid tumors has progressed after treatment for which there are no standard therapies
             available OR histologically and/or cytologically confirmed hematologic malignancies
             that have relapsed, or refractory disease, following at least 2 standard lines of
             systemic therapy for which there are no standard therapies available.

             Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone
             will not be considered a separate systemic treatment regimen.

          6. Must have evaluable or measurable disease.

          7. Has all prior treatment (ie, chemotherapy, immunotherapy, radiotherapy) related
             clinically significant toxicities resolve to ≤ Grade 1 per National Cancer Institute
             Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 or are
             clinically stable and not clinically significant, at time of consent.

          8. All subjects must have completed any prior chemotherapy, targeted therapy and major
             surgery ≥ 28 days before study entry. For daily or weekly chemotherapy without the
             potential for delayed toxicity, a washout period of 14 days or 5 half-lives, whichever
             is shorter may be acceptable, and questions related to this can be discussed with the
             Medical Monitor.

          9. Has normal hepatic function (per NCI-ODWG criteria) as well as adequate hematologic
             (bone marrow [BM] and coagulation factors) and renal function:

               -  Hemoglobin: ≥9 g/dL (90 g/L)

               -  Platelets: ≥75,000/mm³ (≥75 × 10⁹/L)

               -  ANC (Hematologic malignancy subjects): ≥750/mm³ (≥0.75 × 10⁹/L)

               -  ANC (Solid tumor subjects): ≥1,000/mm³ (≥1.0 × 10⁹/L)

               -  PT: <1.5 ULN

               -  PTT: <1.5 ULN

               -  Serum creatinine: ≤1.5 × ULN

               -  Bilirubin and AST: ≤ ULN

             Note: Laboratory results obtained during screening should be used to determine
             eligibility criteria. In situations where laboratory results are outside the permitted
             range, the Investigator may retest the subject and the subsequent within range
             screening result may be used to determine the subject's eligibility. Subjects may be
             retested once within 2 weeks of the screening test. Samples must be reanalyzed at the
             local laboratory.

         10. Able to swallow and retain orally-administered medication and without clinically
             significant gastrointestinal abnormalities that could alter absorption such as
             malabsorption syndrome or major resection of the stomach or bowels.

         11. Manual differential with no significant morphologic abnormalities on complete blood
             count (CBC) testing.

         12. Male subjects must refrain from donating sperm from first dose of Tazemetostat until 3
             months following the last dose of Tazemetostat.

         13. Male subjects with a female partner of childbearing potential must:

               1. Be vasectomized, or

               2. Remain abstinent or use a condom starting at signing of informed consent until 3
                  months following the last dose of study drug. The reliability of sexual
                  abstinence should be evaluated in relation to the duration of the clinical trial
                  and the preferred and usual lifestyle of the subject. Periodic abstinence (eg,
                  calendar, ovulation, sympto-thermal, or post-ovulation methods) and withdrawal
                  are not acceptable methods of contraception.

         14. Female partners of male subjects who are of childbearing potential must also adhere to
             one of the following:

               1. Placement of an intrauterine device or intrauterine system.

               2. Established use of oral, injected, or implanted hormonal methods of contraception
                  plus an additional barrier method.

               3. Progesterone-only oral contraception, where inhibition of ovulation is not the
                  primary mode of action.

         15. Female subjects of childbearing potential:

               1. A woman is considered to be of childbearing potential if she is postmenarchal,
                  has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with
                  no identified cause other than menopause), and has not undergone surgical
                  sterilization (removal of ovaries and/or uterus).

               2. Must agree to remain abstinent (refrain from heterosexual intercourse) or use
                  contraceptive methods that result in a failure rate of < 1% per year starting at
                  least 7 days before the planned first dose of study drug until 6 months following
                  the last dose of study drug.

               3. Examples of contraceptive methods with a failure rate of < 1% per year include
                  bilateral tubal ligation, male sterilization, established and proper use of
                  hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine
                  devices, and copper intrauterine devices.

               4. Due to the potential of enzyme induction with Tazemetostat, female subjects who
                  use hormonal contraceptives should use an additional barrier method of birth
                  control while on study treatment and for 6 months after discontinuation of study
                  treatment.

               5. The reliability of sexual abstinence should be evaluated in relation to the
                  duration of the clinical trial and the preferred and usual lifestyle of the
                  subject. Periodic abstinence (eg, calendar, ovulation, sympto-thermal, or
                  post-ovulation methods) and withdrawal are not acceptable methods of
                  contraception.

               6. Barrier methods must always be supplemented with the use of a spermicide.

         16. Females of childbearing potential must have a negative serum pregnancy test at
             screening.

         17. Has a QT interval corrected by Fridericia's formula (QTcF) ≤450 msec.

         18. Subjects with diagnosed human immunodeficiency virus (HIV) are eligible to participate
             in the study if they meet the following criteria:

               1. No history of AIDS-defining opportunistic infections, or have not had an
                  opportunistic infection within the past 12 months prior to enrollment.

               2. No history of AIDS-defining cancers (eg, Kaposi's sarcoma, aggressive B-cell
                  lymphoma, and invasive cervical cancer).

               3. Subjects may take prophylactic antimicrobials, however subjects that are taking
                  specific antimicrobial drugs where there may be drug-drug interaction or
                  overlapping toxicities should be excluded from study participation.

               4. Subjects should be on established anti-retroviral therapy for at least 4 weeks,
                  and have an HIV viral load of < 400 copies/mL prior to enrollment.

        EXCLUSION CRITERIA:

          1. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
             as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam.
             Subjects with primary glioblastoma multiforme are excluded.

             Note: Subjects with clinically stable brain metastases are eligible to enroll in the
             study.

          2. Clinically significant bleeding diathesis or coagulopathy, including known platelet
             function disorders. Subjects on anticoagulation with low molecular weight heparin are
             allowed.

          3. Known hypersensitivity to any of the components of Tazemetostat.

          4. Use of concurrent investigational agent or anticancer therapy. Note: megestrol
             (Megace) if used as an appetite stimulant is allowed.

               1. Concurrent treatment with bisphosphonates is permitted; however, treatment must
                  be initiated prior to the first dose of Tazemetostat. Prophylactic use of
                  bisphosphonates in subjects without bone disease is not permitted, except for the
                  treatment of osteoporosis.

               2. The concurrent use of all herbal supplements is prohibited during the study as
                  the composition, PK, and metabolism of many herbal supplements are unknown.

          5. Uncontrolled concurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, clinically
             significant cardiac arrhythmias, or psychiatric illness/social situations that would
             limit compliance with study requirements.

          6. Have a known active infection with hepatitis B virus (HBV), as measured by positive
             hepatitis B surface antigen, hepatitis C virus (HCV, as measured by positive hepatitis
             C antibody), OR human T-cell lymphotropic virus 1.

             Exceptions: Subjects with a history of hepatitis B or C who have normal alanine
             aminotransferase (ALT) values and are hepatitis B surface antigen negative and/or have
             undetectable HCV RNA.

          7. Subjects taking medications that are known CYP3A4 inducers or inhibitors (including
             St. John's Wort).

          8. Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet
             and all foods that contain those fruits from 24 hours prior to the first dose of study
             drug until the last dose of study drug.

          9. Any condition or medical problem in addition to the underlying malignancy and organ
             dysfunction that the Investigator feels would pose unacceptable risk.

         10. Has thrombocytopenia, neutropenia, or anemia of grade ≥3 (per CTCAE v5.0 criteria) or
             any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).

         11. Has abnormalities known to be associated with MDS (e.g., del 5q, chr 7 abn) and
             myeloproliferative neoplasms (MPN) (e.g., JAK2 V617F) observed in cytogenetic testing
             and DNA sequencing.

         12. Has a prior history of T-LBL/T-ALL.

         13. Ingestion of alcohol within 72 hours prior to day 1 of Cycle 1, and until the 24, 48
             or 72 hour post dose PK time point has been collected (whichever is the final sampling
             time point). Regular alcohol consumption must not exceed 16 units for males and 7
             units for females per week (1 unit equals 340mL of beer, 115mL of wine, or 43 mL of
             spirits) throughout the study until the end of treatment.

         14. Any form of marijuana use.

         15. History of drug abuse (including alcohol) within the last 6 months prior to screening.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: To evaluate the effect of CYP3A4 inhibition by itraconazole on the steady-state pharmacokinetics (PK) of Tazemetostat when administered as a single and twice daily oral dose in subjects with advanced malignancies, AUC0-t.
Time Frame:0 to 48 hours post-dose on Days 1 - 3. 0 to 72 hours post-dose on Days 15 - 18 and 36 - 39. 0 to 24 hours post-dose on Days 21 - 22. 0 and 2 hours post-dose on Days 25, 28, 31, and 34.
Safety Issue:
Description:AUC0-t: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration

Secondary Outcome Measures

Measure:Part 1: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with itraconazole, and to evaluate the effect of itraconazole on PK of a single 400 mg oral dose of Tazemetostat, AUC0-t.
Time Frame:0 to 48 hours post-dose on Days 1 - 3. 0 to 72 hours post-dose on Days 15 - 18 and 36 - 39. 0 to 24 hours post-dose on Days 21 - 22. 0 and 2 hours post-dose on Days 25, 28, 31, and 34.
Safety Issue:
Description:AUC0-t: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration
Measure:Part 1: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with itraconazole, and to evaluate the effect of itraconazole on PK of a single 400 mg oral dose of Tazemetostat, Cmax.
Time Frame:0 to 48 hours post-dose on Days 1 - 3. 0 to 72 hours post-dose on Days 15 - 18 and 36 - 39. 0 to 24 hours post-dose on Days 21 - 22. 0 and 2 hours post-dose on Days 25, 28, 31, and 34.
Safety Issue:
Description:Cmax: observed maximum plasma concentration
Measure:Part 1: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with itraconazole, and to evaluate the effect of itraconazole on PK of a single 400 mg oral dose of Tazemetostat, Tmax.
Time Frame:0 to 48 hours post-dose on Days 1 - 3. 0 to 72 hours post-dose on Days 15 - 18 and 36 - 39. 0 to 24 hours post-dose on Days 21 - 22. 0 and 2 hours post-dose on Days 25, 28, 31, and 34.
Safety Issue:
Description:Tmax: observed time at Cmax
Measure:Part 1: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with itraconazole, and to evaluate the effect of itraconazole on PK of a single 400 mg oral dose of Tazemetostat, λz.
Time Frame:0 to 48 hours post-dose on Days 1 - 3. 0 to 72 hours post-dose on Days 15 - 18 and 36 - 39. 0 to 24 hours post-dose on Days 21 - 22. 0 and 2 hours post-dose on Days 25, 28, 31, and 34.
Safety Issue:
Description:λz: terminal phase elimination rate constant
Measure:Part 1: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with itraconazole, and to evaluate the effect of itraconazole on PK of a single 400 mg oral dose of Tazemetostat, t1/2.
Time Frame:0 to 48 hours post-dose on Days 1 - 3. 0 to 72 hours post-dose on Days 15 - 18 and 36 - 39. 0 to 24 hours post-dose on Days 21 - 22. 0 and 2 hours post-dose on Days 25, 28, 31, and 34.
Safety Issue:
Description:t1/2: terminal elimination half-life
Measure:Part 2: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with rifampin, AUC0-t.
Time Frame:0 to 48 hours post-dose on Days 1 - 3, 15 - 17 and 24 - 26. 0 and 2 hours post-dose on Days 19 and 21.
Safety Issue:
Description:AUC0-t: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration
Measure:Part 2: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with rifampin, Cmax.
Time Frame:0 to 48 hours post-dose on Days 1 - 3, 15 - 17 and 24 - 26. 0 and 2 hours post-dose on Days 19 and 21.
Safety Issue:
Description:Cmax: observed maximum plasma concentration
Measure:Part 2: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with rifampin, Tmax.
Time Frame:0 to 48 hours post-dose on Days 1 - 3, 15 - 17 and 24 - 26. 0 and 2 hours post-dose on Days 19 and 21.
Safety Issue:
Description:Tmax: observed time at Cmax
Measure:Part 2: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with rifampin, λz.
Time Frame:0 to 48 hours post-dose on Days 1 - 3, 15 - 17 and 24 - 26. 0 and 2 hours post-dose on Days 19 and 21.
Safety Issue:
Description:λz: terminal phase elimination rate constant
Measure:Part 2: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with rifampin, t1/2.
Time Frame:0 to 48 hours post-dose on Days 1 - 3, 15 - 17 and 24 - 26. 0 and 2 hours post-dose on Days 19 and 21.
Safety Issue:
Description:t1/2: terminal elimination half-life
Measure:To evaluate the number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Severity of adverse events experienced by all subjects with at least 1 dose or partial dose of tazemetostat will be evaluated by the Investigator based on the CTCAE, version 5.0.
Measure:To evaluate the number of abnormalities or changes in intensity of conditions noted during the physical exam.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will note any new clinically significant findings (e.g., not noted at screening) or changes in intensity of conditions that occurred after the initial tazemetostat administration.
Measure:To evaluate change in blood pressure.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will note any clinically significant changes from baseline in systolic and diastolic blood pressure measured in units of millimeters of mercury (mmHg).
Measure:To evaluate change in heart rate
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will note any clinically significant changes from baseline in heart rate measured in units of beats per minute (BPM).
Measure:To evaluate change in body temperature.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will note any clinically significant changes from baseline in body temperature measured in degrees Fahrenheit or Celsius.
Measure:To evaluate changes in concomitant medications.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will note any changes in concomitant medications from baseline in all subjects with at least 1 dose or partial dose of tazemetostat.
Measure:To evaluate change in electrical activity of the heartbeat, RR interval.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will report any clinically significant changes from baseline in the RR interval (sec) as noted by a 12 lead electrocardiogram (ECG).
Measure:To evaluate change in electrical activity of the heartbeat, PR interval.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will report any clinically significant changes from baseline in the PR interval (sec) as noted by a 12 lead electrocardiogram (ECG).
Measure:To evaluate change in electrical activity of the heartbeat, QRS complex.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will report any clinically significant changes from baseline in the QRS complex (sec) as noted by a 12 lead electrocardiogram (ECG).
Measure:To evaluate change in electrical activity of the heartbeat, QT interval.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will report any clinically significant changes from baseline in the QT interval (sec) as noted by a 12 lead electrocardiogram (ECG).
Measure:To evaluate changes in clinical laboratory values, hematology.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will note any clinically significant changes in hematological clinical laboratory values from baseline in all subjects with at least 1 dose or partial dose of tazemetostat using laboratory reference ranges.
Measure:To evaluate changes in clinical laboratory values, serum chemistry.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will note any clinically significant changes in serum chemistry clinical laboratory values from baseline in all subjects with at least 1 dose or partial dose of tazemetostat using laboratory reference ranges.
Measure:To evaluate changes in clinical laboratory values, urinalysis.
Time Frame:Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.
Safety Issue:
Description:Investigators will note any clinically significant changes in urinalysis clinical laboratory values from baseline in all subjects with at least 1 dose or partial dose of tazemetostat using laboratory reference ranges.

Details

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

Trial Keywords

  • Epizyme
  • Tazverik
  • Tazemetostat (EPZ-6438)
  • Itraconazole
  • CYP3A4 inhibitor
  • Rifampin
  • CYP3A4 inducer
  • Drug-Drug Interaction (DDI)
  • Pharmacokinetics (PK)

Last Updated

August 31, 2020