A Phase I, Open-Label, Multicenter, Three-Period, One-Sequence Study to Investigate the Effect of Rifampin on the Pharmacokinetics of a Single Oral Dose of 960 mg of Vemurafenib
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 主要终点
- Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib
研究概览
简要总结
This open-label, multi-center, three-period, one-sequence study will investigate the effect of rifampin on the PK of vemurafenib in participants with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Eligible participants will have the option to continue treatment with vemurafenib as part of an extension study GO28399 (NCT01739764).
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 either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAF V600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a Deoxyribonucleic acid (DNA) sequencing method, and who have no acceptable standard treatment options
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Life expectancy of greater than or equal to (>/=) 12 weeks
- •Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment
- •Adequate hematologic and end organ function
- •Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use 2 effective methods of contraception
- •Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential
排除标准
- •Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
- •Requirement for immediate or urgent treatment with daily vemurafenib and for whom the intermittent schedule of vemurafenib employed during the 24-day period for this trial is not clinically acceptable
- •Allergy or hypersensitivity to components of the vemurafenib formulation
- •Experimental therapy within 4 weeks prior to first dose of study drug
- •Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug, or anticipation of the need for major surgery during study treatment
- •Prior anti-cancer therapy within 28 days before the first dose of study drug
- •History of clinically significant cardiac or pulmonary dysfunction
- •History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
- •History of myocardial infarction within 6 months prior to first dose of study drug
- •Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
- •History of congenital long QT syndrome or corrected QT interval (QTc) greater than (>) 450 milliseconds
- •Active central nervous system lesions
- •Uncontrolled or poorly controlled diabetes
- •Current severe, uncontrolled systemic disease
研究组 & 干预措施
Vemurafenib + Rifampin
There will be 3 intervention periods in the study: Period A (Days 1 to 7), Period B (Days 8 to 16), and Period C (Days 17 to 24). Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 milligrams (mg) as film-coated tablets orally alone on Day 1 (Period A); with rifampin (at a dose of 600 mg as capsules orally) on Day 17 (Period C); and rifampin alone at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).
干预措施: Rifampin (Drug)
Vemurafenib + Rifampin
There will be 3 intervention periods in the study: Period A (Days 1 to 7), Period B (Days 8 to 16), and Period C (Days 17 to 24). Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 milligrams (mg) as film-coated tablets orally alone on Day 1 (Period A); with rifampin (at a dose of 600 mg as capsules orally) on Day 17 (Period C); and rifampin alone at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).
干预措施: Vemurafenib (Drug)
结局指标
主要结局
Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib
时间窗: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
AUClast is the area under the vemurafenib plasma concentration versus time curve from time zero to the time of last measured concentration of vemurafenib (Tlast). Area under the curve (AUC) is a measure of the plasma concentration of a drug over time. AUClast is presented in micrograms times (\*) hour per milliliter (mcg\*h/mL).
Area Under the Plasma Concentration Time-curve From Zero to Extrapolated Infinite Time (AUC[0-inf]) of Vemurafenib
时间窗: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
AUC(0-inf) is the AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in mcg\*h/mL.
Maximum Observed Plasma Concentration (Cmax) of Vemurafenib
时间窗: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Cmax is the maximum observed plasma vemurafenib concentration, presented in microgram per milliliter (mcg/mL).
次要结局
未报告次要终点