A Randomized, 5-Period, Crossover Study in Healthy Subjects to Assess the Bioequivalence of Atazanavir When Co-Administered With Cobicistat as a Fixed Dose Combination Relative to the Single Agents Following a Light Meal, the Relative Bioavailability of Atazanavir When Co-Administered With Cobicistat as a Fixed Dose Combination Relative to the Single Agents Under Fasted Conditions, and the Effect of Food on the Bioavailability of Atazanavir in the Fixed Dose Combination
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Quantifiable Concentration (AUC[0-T]) and From Time 0 to Infinity (AUC[INF]) for Atazanavir
研究概览
简要总结
The purpose of the study is to compare the pharmacokinetics and bioequivalence of atazanavir in a fixed-dose combination with cobicistat with that of atazanavir coadministered with cobicistat as single agents.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy men and women, ages 18 to 49 years
- •Body mass index 18 to 32 kg/m^2, inclusive
- •Women of childbearing potential (WOCBP) who were not pregnant or breastfeeding
- •WOCBP and men who are sexually active with WOCBP must use acceptable contraceptive methods
排除标准
- •Any significant acute or chronic medical illness
- •Current or recent (within 3 months of study drug administration) gastrointestinal tract disease
- •Any major surgery within 4 weeks of study drug administration
- •Any gastrointestinal tract surgery (including cholecystectomy) that could have an impact on the absorption of study drug
- •Donation of blood to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration (within 2 weeks for plasma only)
- •Blood transfusion within 4 weeks of study drug administration
- •Inability to tolerate oral medication, to be venipunctured, or to tolerate venous access
- •Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination or electrocardiogram (ECG) findings, vital sign measurements, or results of clinical laboratory tests, beyond what is consistent with the target population
- •Any of the following 12-lead ECG findings prior to study drug administration, confirmed by repeat testing
- •PR ≥210 msec
- •QRS ≥120 msec
- •QT ≥500 msec
- •QTcF ≥450 msec
- •2nd- or 3rd-degree A-V block or clinically relevant abnormalities in ECG findings
- •Positive result on urine screening for drugs of abuse
- •Positive result on blood screening for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 or -2 antibody
- •Laboratory test results indicating levels outside of the ranges specified below:
- •Alanine aminotransferase >upper limit of normal (ULN)
- •Aspartate aminotransferase >ULN
- •Total bilirubin >ULN
- •Serum creatinine >ULN
研究组 & 干预措施
Treatment A: Atazanavir + Cobicistat coadministered
Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, following a light meal on Day 1 or 8
干预措施: Atazanavir (Drug)
Treatment A: Atazanavir + Cobicistat coadministered
Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, following a light meal on Day 1 or 8
干预措施: Cobicistat (Drug)
Treatment B: Atazanavir/Cobicistat FDC
Participants received a single fixed-dose combination (FDC) of atazanavir, 300 mg/cobicistat, 150 mg, following a light meal on Day 1 or 8
干预措施: Atazanavir/Cobicistat FDC (Drug)
Treatment C: Atazanavir + Cobicistat coadministered
Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, in the fasted state on Day 15 or 22
干预措施: Atazanavir (Drug)
Treatment C: Atazanavir + Cobicistat coadministered
Participants received a single dose of atazanavir, 300 mg as capsule, coadministered with cobicistat,150 mg as tablet, in the fasted state on Day 15 or 22
干预措施: Cobicistat (Drug)
Treatment D: Atazanavir/Cobicistat FDC
Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, in the fasted state on Day 15 or 22
干预措施: Atazanavir/Cobicistat FDC (Drug)
Treatment E: Atazanavir/Cobicistat FDC
Participants received a single FDC dose of atazanavir, 300 mg/cobicistat, 150 mg, following a high-fat meal on Day 29
干预措施: Atazanavir/Cobicistat FDC (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Quantifiable Concentration (AUC[0-T]) and From Time 0 to Infinity (AUC[INF]) for Atazanavir
时间窗: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)
Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. AUC(0-T) and AUC(INF) were derived from plasma concentration versus time data.
Maximum Observed Plasma Concentration (Cmax) of Atazanavir
时间窗: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)
Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. Cmax was derived from plasma concentration versus time data.
次要结局
- Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests(At Screening and on Days -1,4, 11, 18, and 31 (study discharge))
- Observed Concentration at 24 Hours (C24) of Atazanavir(Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose))
- Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings(At screening; on Day -1; predose and 4 hours postdose on Days 1, 18, 15, 22, and 29; and at study discharge (Day 31))
- Time of Maximum Observed Concentration (Tmax) of Atazanavir(Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose))
- Apparent Terminal Half-life (T-HALF) of Atazanavir(Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose))
- Time of Maximum Observed Concentration (Tmax) of Cobicistat(Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose))
- Area Under the Concentration Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-T]) and Area Under the Concentration Curve From Time 0 to Infinity (AUC[INF]) of Cobicistat(Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose))
- Number of Participants Who Died and With Serious Adverse Events (SAEs)(On Day 24 or 31)
- Maximum Observed Plasma Concentration (Cmax) of Cobicistat(Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose))
- T-HALF of Cobicistat(Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose))