A Two-part, Phase I, Open-label, Multicenter, Two-period, One-sequence Study to Investigate the Effect of Itraconazole and Rifampin on the PK of Vemurafenib at Steady State
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 11
- 主要终点
- Area under the concentration-time curve From Time 0 to 12 Hours Postdose (AUC0-12)
研究概览
简要总结
This is a two-part, Phase 1, open-label, multicenter, two-period, one-sequence study to investigate the effect of itraconazole and rifampin on the PK of vemurafenib following multiple 960 milligrams (mg) twice daily (BID) dosing in adult participants with unresectable Stage IIIC or Stage IV metastatic melanoma positive for the BRAF V600 mutation, or other malignant tumor types that harbor a V600-activating mutation of BRAF where the participant has no acceptable standard treatment options.
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
- •Participants with age greater than or equal to (>=) 18 years with either unresectable Stage IIIC or Stage IV metastatic melanoma positive for the BRAF V600 mutation, or other malignant tumor types that harbor a V600-activating mutation of BRAF
- •Eastern Cooperative Oncology Group Performance Status 0 to 2
- •Life expectancy >=12 weeks
- •Adequate hematologic and end organ function obtained within 2 weeks prior to first dose of study drug
- •Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use two effective methods of contraception including at least one method with a failure rate of <1% per year during the course of the study and for at least 6 months after completion of study treatment
- •Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential
- •Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
排除标准
- •Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Study Day 1 of Period A
- •Allergy or hypersensitivity to components of the vemurafenib formulation
- •Experimental therapy within 4 weeks prior to first dose of study drug treatment on Study Day 1 of Period A
- •Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug treatment on Study Day 1 of Period A, or anticipation of the need for major surgery during study treatment
- •Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy) within 28 days (6 weeks for nitrosoureas or mitomycin C, and 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment on Study Day 1 of Period A.
研究组 & 干预措施
Part 1: Vemurafenib+Itraconazole
Part 1: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with itraconazole orally once in the morning from Days 21 to 40 (Period B).\nPart 2: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with rifampin orally once in the morning from Days 21 to 40 (Period B).
干预措施: Itraconazole (Drug)
Part 1: Vemurafenib+Itraconazole
Part 1: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with itraconazole orally once in the morning from Days 21 to 40 (Period B).\nPart 2: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with rifampin orally once in the morning from Days 21 to 40 (Period B).
干预措施: Rifampin (Drug)
Part 1: Vemurafenib+Itraconazole
Part 1: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with itraconazole orally once in the morning from Days 21 to 40 (Period B).\nPart 2: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with rifampin orally once in the morning from Days 21 to 40 (Period B).
干预措施: Vemurafenib (Drug)
结局指标
主要结局
Area under the concentration-time curve From Time 0 to 12 Hours Postdose (AUC0-12)
时间窗: Period A and B: Pre-morning dose on Day 18, 19, and 20 and 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose on Day 20
Maximum observed concentration (Cmax)
时间窗: Period A and B: Pre-morning dose on Day 18, 19, and 20 and 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose on Day 20
Time to maximum concentration (Tmax)
时间窗: Period A and B: Pre-morning dose on Day 18, 19, and 20 and 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose on Day 20
次要结局
- Incidence of adverse events(28 days after last dose of study treatment (last dose = Day 40))