Open-Label, Multicenter, Two-Part, Phase 1 Study to Characterize Effects of a Moderate CYP3A Inhibitor on PK of Tazemetostat, Effects of Tazemetostat on PK of CYP2C8 and CYP2C19 Substrates, and Effect of Increased Gastric pH on PK of Tazemetostat in B-cell Lymphoma or Advanced Solid Tumor Patients
- Registration Number
- NCT03028103
- Lead Sponsor
- Epizyme, Inc.
- Brief Summary
This is a Phase 1, open-label, two-part, safety, PK, and activity study designed to characterize the DDI potential of tazemetostat. Tazemetostat will be taken orally BID continuously in 28-day cycles in both study parts.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
Inclusion Criteria
Not provided
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Exclusion Criteria
Not provided
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part A and B Tazemetostat Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25. Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19. Part A and B Omeprazole Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25. Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19. Part A and B Repaglinide Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25. Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19. Part A and B Fluconazole Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25. Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.
- Primary Outcome Measures
Name Time Method Part B: Cmax of Omeprazole During Co-administration With Tazemetostat Days 1 and 16, 0 to 8 hours post-dose Part A: Effect of CYP3A Inhibition by Fluconazole on the PK of Tazemetostat (AUC0-t, AUC0-8) Days 15 and 19, 0 to 8 hours post-dose Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C19 Using Omeprazole as Probe a Substrate (AUC0-t, AUC0-∞) Days 1 and 16, 0 to 8 hours post-dose Part A: Cmax of Tazemetostat During Co-administration With Fluconazole Days 15 and 19, 0 to 8 hours post-dose Part B: Cmax of Repaglinide During Co-administration With Tazemetostat Days 1 and 16, 0 to 8 hours post-dose Part B: Cmax of Tazemetostat During Co-administration With Omeprazole Days 16 and 19, 0 to 8 hours post-dose Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C8 Using Repaglinide as a Probe Substrate (AUC0-t, AUC0-∞) Days 1 and 16, 0 to 8 hours post-dose Part B: Effect of Increased Gastric pH by Omeprazole on the PK of Tazemetostat (AUC0-t, AUC0-8) Days 16 and 19, 0 to 8 hours post-dose
- Secondary Outcome Measures
Name Time Method Incidence of Treatment-emergent Adverse Events as a Measure of Safety From the first dose of study treatment until the earlier of either 30 days after the discontinuation of study treatment or until the initiation of subsequent anticancer therapy, up to 2 years. Part A: Tmax of Tazemetostat After Administration Alone and With Fluconazole Days 15 and 19, 0 to 8 hours post-dose Part A: Cmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole Days 15 and 19, 0 to 8 hours post-dose Part A: t1/2 of Tazemetostat After Administration Alone and With Fluconazole Days 15 and 19, 0 to 8 hours post-dose Part A: Tmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole Days 15 and 19, 0 to 8 hours post-dose Part A: PK of Tazemetostat and Its Metabolites After Administration Alone and With Fluconazole (AUC0-t, AUC0-8) Days 15 and 19, 0 to 8 hours post-dose Part A: t1/2 of Tazemetostat Metabolites After Administration Alone and With Fluconazole Days 15 and 19, 0 to 8 hours post-dose Part A: Exposure of Fluconazole After Administration of 400 mg Once Daily for 4 Days (AUC0-8) Day 19, 0 to 8 hours post-dose Part A: Cmax of Fluconazole After Administration of 400mg Once Daily for 4 Days Day 19, 0 to 8 hours post-dose Part A: Tmax of Fluconazole After Administration of 400mg Once Daily for 4 Days Day 19, 0 to 8 hours post-dose The Antitumor Activity of Tazemetostat Will be Assessed in Patients With Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) or Advanced Solid Tumors . Within 28 days of Day 1, 8 weeks, 16 weeks, 24 weeks Objective response rate (ORR: complete response \[CR\] or PR) and disease control rate (DCR: CR or PR, or stable disease lasting 24 weeks or longer from start of treatment with tazemetostat) using Lugano Classification for subjects with lymphoma, or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with solid tumors.
Trial Locations
- Locations (3)
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States