A Single-Dose, Open-Label, 3-Panel, Randomized, Pivotal Crossover Study to Assess the Bioequivalence of Darunavir When Co-Administrated With Cobicistat as Either a Fixed Dose Combination Tablet (G006) or as Single Agents Under Fed and Fasted Conditions in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 133
- 主要终点
- Comparison of maximum plasma analyte concentration (Cmax) of darunavir as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg)
研究概览
简要总结
The purpose of this study is to evaluate the single-dose pharmacokinetics and bioequivalence of darunavir 800 mg when administered as a fixed dose combination relative to 2 x 400 mg tablets of the commercial tablet formulation, in the presence of 150 mg cobicistat, (under fed and fasted conditions) in healthy participants.
详细描述
This is a randomized (the study drug is assigned by chance), open-label (all people know the identity of the intervention), 3-panel, single-center, single-dose, crossover (method used to switch patients from one treatment arm to another in a clinical trial) study in 134 healthy adult participants. The study consists of 3 phases including a screening phase of approximately 3 weeks (Days -21 to -1) followed by an open-label treatment phase consisting of 3 panels with 2 single-dose treatment sessions of 5 days each (Days -1 to 4) separated by a washout period of at least 7 days, and a follow-up period occurring 7 to 10 days after last intake of study drugs. The study consists of 3 panels. In each panel participants will be randomly be assigned to 1 of 2 treatment sequences (AB or BA for Panel 1; CD or DC for Panel 2; and EF or FE for Panel 3). Participants will receive either single-dose darunavir 800 mg as 2 x 400 mg tablets and cobicistat 150 mg tablet or single-dose darunavir/cobicistat 800/150 mg as tablet in each panel (under fed and fasted conditions).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant should be healthy on the basis of physical examination, medical history, vital signs, and electrocardiogram and clinical laboratory tests performed at screening
- •Have a Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.5 to 30.0 kg/m2, extremes included
- •Men and women must agree to use a highly effective method of birth control
排除标准
- •Has a positive HIV-1 or HIV-2 test at screening
- •Has a Hepatitis A, B or C infection (confirmed by hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody, respectively) at screening
- •Has any history of renal insufficiency
- •Has a history of significant skin reactions or any history of allergies to drugs
研究组 & 干预措施
Treatment A
Single-dose co-administration of 800 mg darunavir and 150 mg cobicistat as single agents (under fasted condition)
干预措施: darunavir (Drug)
Treatment A
Single-dose co-administration of 800 mg darunavir and 150 mg cobicistat as single agents (under fasted condition)
干预措施: cobicistat (Drug)
Treatment B
Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fasted condition).
干预措施: darunavir (Drug)
Treatment B
Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fasted condition).
干预措施: cobicistat (Drug)
Treatment C
Single-dose co-administration of 800 mg darunavir and 150 mg cobicistat as single agents (under fed condition - standardized breakfast).
干预措施: darunavir (Drug)
Treatment C
Single-dose co-administration of 800 mg darunavir and 150 mg cobicistat as single agents (under fed condition - standardized breakfast).
干预措施: cobicistat (Drug)
Treatment D
Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - standardized breakfast).
干预措施: darunavir (Drug)
Treatment D
Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - standardized breakfast).
干预措施: cobicistat (Drug)
Treatment E
Single-dose co-administration of the fixed dose combination darunavir/cobicistat 800/150-mg (under fasted condition).
干预措施: darunavir (Drug)
Treatment E
Single-dose co-administration of the fixed dose combination darunavir/cobicistat 800/150-mg (under fasted condition).
干预措施: cobicistat (Drug)
Treatment F
Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - high-fat breakfast).
干预措施: darunavir (Drug)
Treatment F
Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - high-fat breakfast).
干预措施: cobicistat (Drug)
结局指标
主要结局
Comparison of maximum plasma analyte concentration (Cmax) of darunavir as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg)
时间窗: Up to 27 Days
The pharmacokinetic parameter (Cmax) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg).
Comparison of last observed measurable analyte concentration (Clast) of darunavir as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg)
时间窗: Up to 27 Days
The pharmacokinetic parameter (Clast) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg).
Comparison of actual sampling time to reach the maximum plasma analyte concentration (tmax) of darunavir as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg)
时间窗: Up to 27 Days
The pharmacokinetic parameter (tmax) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg) for assessment of bioequivalance.
Area under curve from time of administration up to the last time point with a measurable plasma analyte concentration (AUClast) of darunavir as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg)
时间窗: Up to 27 Days
The pharmacokinetic parameter (AUClast) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg).
次要结局
- Number of participants with adverse events as a measure of safety and tolerabilty(Up to 27 Days)
- Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a fixed dose combination tablet(Up to 27 Days)
- Evaluation of plasma pharmacokinetics of cobicistat with darunavir when both administered as a single agents(Up to 27 Days)
- Evaluation of effect of a high-fat meal on darunavir and cobicistat pharmacokinetics relative to the fasted state(Up to 27 Days)