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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 3
- 主要终点
- Part B: Cmax of Omeprazole During Co-administration With Tazemetostat
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: Tazemetostat (Drug)
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.
干预措施: Fluconazole (Drug)
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.
干预措施: Omeprazole (Drug)
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.
干预措施: Repaglinide (Drug)
结局指标
主要结局
Part B: Cmax of Omeprazole During Co-administration With Tazemetostat
时间窗: 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)
时间窗: 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-∞)
时间窗: Days 1 and 16, 0 to 8 hours post-dose
Part A: Cmax of Tazemetostat During Co-administration With Fluconazole
时间窗: Days 15 and 19, 0 to 8 hours post-dose
Part B: Cmax of Repaglinide During Co-administration With Tazemetostat
时间窗: Days 1 and 16, 0 to 8 hours post-dose
Part B: Cmax of Tazemetostat During Co-administration With Omeprazole
时间窗: 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-∞)
时间窗: 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)
时间窗: Days 16 and 19, 0 to 8 hours post-dose
次要结局
- 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)