Phase I, Single-center, Open Label, Fixed-sequence Cross-over Study to Evaluate the Effect of Rifabutin on the Pharmacokinetics of Oral Cabotegravir in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Assessment of Plasma CAB Pharmacokinetic (PK) Parameter: Area Under the Concentration-time Curve Over One Dosing Interval (AUC [0 to Tau])
研究概览
简要总结
This is a Phase I, single-center, open-label, fixed-sequence, 2-period crossover study in healthy adults to evaluate the effect of oral rifabutin (RBT) 300 milligram (mg) on the pharmacokinetics of oral cabotegravir (CAB) 30 milligram ( mg). This study will evaluate the drug-drug interaction (DDI) potential between CAB and RBT to inform dosing strategies for tuberculosis in subjects receiving CAB for human immunodeficiency virus (HIV) treatment or prevention. In Treatment Period 1 (Treatment A) participants will receive CAB 30 mg once daily for 14 days, followed by Treatment Period 2 (Treatment B) where participants will receive RBT 300 mg once daily with CAB 30 mg once daily for 14 days. The total study duration will be approximately for 10 weeks. Approximately 15 healthy subjects will be enrolled to ensure that 12 subjects complete dosing and critical assessments.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Treatment A
Participants will be administered a single oral dose of CAB 30 mg after an overnight fast of at least 6 hours for 14 days in Period 1. Dosing of study medication on non-PK days may be with or without food.
干预措施: Cabotegravir (Drug)
Treatment B
Participants will be administered a single dose of RBT 300 mg and a single dose of CAB 30 mg after an overnight fast of at least 6 hours once daily for 14 days in Period 2. Dosing of study medication on non-PK days may be with or without food.
干预措施: Cabotegravir (Drug)
Treatment B
Participants will be administered a single dose of RBT 300 mg and a single dose of CAB 30 mg after an overnight fast of at least 6 hours once daily for 14 days in Period 2. Dosing of study medication on non-PK days may be with or without food.
干预措施: Rifabutin (Drug)
结局指标
主要结局
Assessment of Plasma CAB Pharmacokinetic (PK) Parameter: Area Under the Concentration-time Curve Over One Dosing Interval (AUC [0 to Tau])
时间窗: Pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28
Blood samples for PK analysis of CAB were collected at pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28. AUC (0 to tau) was calculated using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. PK Summary Population included participants who had CAB PK parameter estimates from both serial PK sampling time periods 1 and 2. Comparisons were made for the repeated dose PK parameters of CAB when given alone in Period 1 and when co-administered with steady-state RBT in Period 2.
Assessment of Plasma CAB PK Parameter: Maximum Observed Concentration (Cmax)
时间窗: Pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28
Blood samples for PK analysis of CAB were collected at pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28. Cmax was determined directly from the concentration-time data. Comparisons were made for the repeated dose PK parameters of CAB when given alone in Period 1 and when co-administered with steady-state RBT in Period 2.
次要结局
- Assessment of Hematology Parameters: Erythrocytes Distribution Width (EDW)(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Plasma CAB PK Parameter: Concentration at the End of the Dosing Interval (Ctau)(Pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28)
- Assessment of Plasma CAB PK Parameter: Time of Occurrence of Cmax (Tmax)(Pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28)
- Assessment of Plasma CAB PK Parameter: Terminal Phase Half-life (t1/2)(Pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28)
- Concurrent Medication Assessment in Treatment Period 1 and 2(Up to 10 weeks)
- Assessment of Plasma CAB PK Parameter: The Apparent Oral Clearance (CL/F)(Pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 10 weeks)
- Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Hematology Parameters: Hematocrit and Reticulocytes/Erythrocytes (R/E)(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Hematology Parameter: Hemoglobin(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Hematology Parameter: Eryrocyte Mean Corpuscular Hemoglobin(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Hematology Parameter: Erythrocye Mean Corpuscular Volume(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Hematology Parameters: Erythrocytes and Reticulocytes(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium and Urea(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Clinical Chemistry Parameters: Albumin and Protein(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK) and Gamma Glutamyl Transferase (GGT)(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Assessment of Clinical Chemistry Parameters: Direct Bilirubin (DB), Bilirubin and Creatinine(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Number of Participants With Abnormal Urinalysis Result(Day -1, Day 13, Day 21, Day 27 and follow-up (10 to 14 days after last dose))
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings(Day 1, 14, 21, 28 and follow-up (10 to 14 days after last dose))
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline to follow-up (10 to 14 days after last dose))
- Change From Baseline in Pulse Rate(Baseline to follow-up (10 to 14 days after last dose))