An Open-Label, Multicenter, Two-Part, Phase 1 Study to Characterize the Effects of a Moderate CYP3A Inhibitor on the Pharmacokinetics of Tazemetostat (EPZ-6438) (Part A), the Effects of Tazemetostat on the Pharmacokinetics of CYP2C8 and CYP2C19 Substrates, and the Effect of Increased Gastric pH on the Pharmacokinetics of Tazemetostat (Part B) in Subjects With B-cell Lymphoma or Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Tazemetostat
- Conditions
- Diffuse Large B Cell Lymphoma
- Sponsor
- Epizyme, Inc.
- Enrollment
- 32
- Locations
- 3
- Primary Endpoint
- Part B: Cmax of Omeprazole During Co-administration With Tazemetostat
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part A and B
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.
Intervention: Tazemetostat
Part A and B
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.
Intervention: Fluconazole
Part A and B
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.
Intervention: Omeprazole
Part A and B
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.
Intervention: Repaglinide
Outcomes
Primary Outcomes
Part B: Cmax of Omeprazole During Co-administration With Tazemetostat
Time Frame: 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)
Time Frame: 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-∞)
Time Frame: Days 1 and 16, 0 to 8 hours post-dose
Part A: Cmax of Tazemetostat During Co-administration With Fluconazole
Time Frame: Days 15 and 19, 0 to 8 hours post-dose
Part B: Cmax of Repaglinide During Co-administration With Tazemetostat
Time Frame: Days 1 and 16, 0 to 8 hours post-dose
Part B: Cmax of Tazemetostat During Co-administration With Omeprazole
Time Frame: 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-∞)
Time Frame: 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)
Time Frame: Days 16 and 19, 0 to 8 hours post-dose
Secondary Outcomes
- 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)