A Phase I, Two-Panel, Open-Label, Randomized, 3-way Crossover Trial in Healthy Subjects to Determine the Relative Oral Bioavailability of TMC207 After Single Dose Administration of TMC207 100 mg as the Phase II Clinical Trial Tablet Formulation and as a Newly Developed Tablet Formulation, Under Fed and Fasted Conditions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 主要终点
- Time to Reach the Maximum Plasma Concentration of TMC207
研究概览
简要总结
The purpose of this study is to determine the relative oral bioavailability (the extent to which a medication or other substance becomes available to the body as compared with another form of medication or other substance) of TMC207 after single-dose oral administration of the Phase II clinical study tablet formulation, and a newly developed tablet formulations, under fed (with food) and fasted (without food) conditions.
详细描述
This is a 2-panel (2 groups), open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), 3- way crossover (method used to switch participants from one treatment arm to another in a clinical study) study. The study consists of 3 phases including, the screening phase (less than or equal to 21 days before administration of study medication), treatment phase (84 days), and the follow-up phase (up to 30 to 35 days after the last blood sample in the last treatment session is collected). Approximately 24 healthy participants will be allocated to one of two panels: Panel A (participants will receive study medication under fed condition); and Panel B (participants will receive study medication under fasted condition). Participants in Panel A will be randomly assigned to 1 of 6 treatment sequences (Treatment sequences ABC, ACB, BAC, BCA, CBA, and CAB) to receive the following 3 formulations of TMC207 with food: Treatments A: the Phase II tablet formulation; Treatment B: newly developed tablet formulation with fine particle size distribution; and Treatment C: newly developed tablet formulation with coarse particle size distribution. Participants in Panel B will be randomly assigned to 1 of 6 treatment sequences (Treatment sequences DEF, DFE, EDF, EFD, FDE, and FED) to receive the following 3 formulations of TMC207 without food: Treatments D: the Phase II tablet formulation; Treatment E: newly developed tablet formulation with fine particle size distribution; and Treatment F: newly developed tablet formulation with coarse particle size distribution. Subsequent treatments will be separated by a period of 4 weeks. The total duration of the study for each participant will be approximately 20 weeks. Safety evaluations will include assessment of adverse events, clinical laboratory tests, vital signs, electrocardiogram, physical examination, and alcohol urine medicine screen which will be monitored throughout the study.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Non-smoker or smokers with no more than 10 cigarettes or 2 cigars or 2 pipes per day for at least 3 months prior selection
- •Normal weight as defined by a body mass index (weight in kilograms divided by the square of height in meters) of 18 to 30 kg/m2, extremes included
- •Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality
排除标准
- •Positive tests for Human Immunodeficiency Virus 1 (HIV type 1) or HIV 2; hepatitis A, hepatitis B, or hepatitis C infection; and urine drug tests at screening
- •Female with no childbearing potential
- •History or current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use
- •Relevant medical history or presence of systemic disease (gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, infectious disease), or significant skin disease
- •History or presence of clinically significant electrocardiogram at screening
- •Abnormal laboratory values at screening
研究组 & 干预措施
Panel A: Treatment Sequence ABC
Participants will receive the 3 treatments (Treatment A,B and C) in sequence ABC with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment A (Drug)
Panel A: Treatment Sequence ABC
Participants will receive the 3 treatments (Treatment A,B and C) in sequence ABC with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment B (Drug)
Panel A: Treatment Sequence ABC
Participants will receive the 3 treatments (Treatment A,B and C) in sequence ABC with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment C (Drug)
Panel A: Treatment Sequence ACB
Participants will receive the 3 treatments (Treatment A,B and C) in sequence ACB with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment A (Drug)
Panel A: Treatment Sequence ACB
Participants will receive the 3 treatments (Treatment A,B and C) in sequence ACB with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment B (Drug)
Panel A: Treatment Sequence ACB
Participants will receive the 3 treatments (Treatment A,B and C) in sequence ACB with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment C (Drug)
Panel A: Treatment Sequence BAC
Participants will receive the 3 treatments (Treatment A,B and C) in sequence BAC with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment A (Drug)
Panel A: Treatment Sequence BAC
Participants will receive the 3 treatments (Treatment A,B and C) in sequence BAC with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment B (Drug)
Panel A: Treatment Sequence BAC
Participants will receive the 3 treatments (Treatment A,B and C) in sequence BAC with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment C (Drug)
Panel A: Treatment Sequence BCA
Participants will receive the 3 treatments (Treatment A,B and C) in sequence BCA with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment A (Drug)
Panel A: Treatment Sequence BCA
Participants will receive the 3 treatments (Treatment A,B and C) in sequence BCA with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment B (Drug)
Panel A: Treatment Sequence BCA
Participants will receive the 3 treatments (Treatment A,B and C) in sequence BCA with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment C (Drug)
Panel A: Treatment Sequence CBA
Participants will receive the 3 treatments (Treatment A,B and C) in sequence CBA with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment A (Drug)
Panel A: Treatment Sequence CBA
Participants will receive the 3 treatments (Treatment A,B and C) in sequence CBA with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment B (Drug)
Panel A: Treatment Sequence CBA
Participants will receive the 3 treatments (Treatment A,B and C) in sequence CBA with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment C (Drug)
Panel A: Treatment Sequence CAB
Participants will receive the 3 treatments (Treatment A,B and C) in sequence CAB with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment A (Drug)
Panel A: Treatment Sequence CAB
Participants will receive the 3 treatments (Treatment A,B and C) in sequence CAB with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment B (Drug)
Panel A: Treatment Sequence CAB
Participants will receive the 3 treatments (Treatment A,B and C) in sequence CAB with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment C (Drug)
Panel B: Treatment Sequence DEF
Participants will receive the 3 treatments (Treatment D,E and F) in sequence DEF with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment D (Drug)
Panel B: Treatment Sequence DEF
Participants will receive the 3 treatments (Treatment D,E and F) in sequence DEF with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment E (Drug)
Panel B: Treatment Sequence DEF
Participants will receive the 3 treatments (Treatment D,E and F) in sequence DEF with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment F (Drug)
Panel B: Treatment Sequence DFE
Participants will receive the 3 treatments (Treatment D,E and F) in sequence DFE with food and subsequent treatments will be separated by 4 weeks..
干预措施: Treatment D (Drug)
Panel B: Treatment Sequence DFE
Participants will receive the 3 treatments (Treatment D,E and F) in sequence DFE with food and subsequent treatments will be separated by 4 weeks..
干预措施: Treatment E (Drug)
Panel B: Treatment Sequence DFE
Participants will receive the 3 treatments (Treatment D,E and F) in sequence DFE with food and subsequent treatments will be separated by 4 weeks..
干预措施: Treatment F (Drug)
Panel B: Treatment Sequence EDF
Participants will receive the 3 treatments (Treatment D,E and F) in sequence EDF with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment D (Drug)
Panel B: Treatment Sequence EDF
Participants will receive the 3 treatments (Treatment D,E and F) in sequence EDF with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment E (Drug)
Panel B: Treatment Sequence EDF
Participants will receive the 3 treatments (Treatment D,E and F) in sequence EDF with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment F (Drug)
Panel B: Treatment Sequence EFD
Participants will receive the 3 treatments (Treatment D,E and F) in sequence EFD with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment D (Drug)
Panel B: Treatment Sequence EFD
Participants will receive the 3 treatments (Treatment D,E and F) in sequence EFD with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment E (Drug)
Panel B: Treatment Sequence EFD
Participants will receive the 3 treatments (Treatment D,E and F) in sequence EFD with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment F (Drug)
Panel B: Treatment Sequence FDE
Participants will receive the 3 treatments (Treatment D,E and F) in sequence FDE with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment D (Drug)
Panel B: Treatment Sequence FDE
Participants will receive the 3 treatments (Treatment D,E and F) in sequence FDE with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment E (Drug)
Panel B: Treatment Sequence FDE
Participants will receive the 3 treatments (Treatment D,E and F) in sequence FDE with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment F (Drug)
Panel B: Treatment Sequence FED
Participants will receive the 3 treatments (Treatment D,E and F) in sequence FED with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment D (Drug)
Panel B: Treatment Sequence FED
Participants will receive the 3 treatments (Treatment D,E and F) in sequence FED with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment E (Drug)
Panel B: Treatment Sequence FED
Participants will receive the 3 treatments (Treatment D,E and F) in sequence FED with food and subsequent treatments will be separated by 4 weeks.
干预措施: Treatment F (Drug)
结局指标
主要结局
Time to Reach the Maximum Plasma Concentration of TMC207
时间窗: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
Maximum Plasma Concentration of TMC207
时间窗: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
Area Under Curve From Time of Administration up to 72 Hours Post Dosing of TMC207
时间窗: 0 hour predose to 672 hours postdose, after each of the 3 single-dose administration
次要结局
- Time to Reach the Maximum Plasma Concentration of M2 Metabolite of TMC207(0 hour predose to 672 hours postdose, after each of the 3 single-dose administration)
- Maximum Plasma Concentration of M2 Metabolite of TMC207(0 hour predose to 672 hours postdose, after each of the 3 single-dose administration)
- Area Under Curve From Time of Administration up to 72 Hours Post Dosing of M2 Metabolite of TMC207(0 hour predose to 672 hours postdose, after each of the 3 single-dose administration)
- Area Under Curve From Time of Administration up to the Last Time Point With a Measurable Concentration Post Dosing of M2 Metabolite of TMC207(0 hour predose to 672 hours postdose, after each of the 3 single-dose administration)
- Area Under Curve Extrapolated to Infinity of M2 Metabolite of TMC207(0 hour predose to 672 hours postdose, after each of the 3 single-dose administration)
- Elimination Rate Constant of a Sequential Elimination Phase of the Plasma Concentration-Time Curve of M2 Metabolite of TMC207(0 hour predose to 672 hours postdose, after each of the 3 single-dose administration)
- Elimination Half-Life of M2 Metabolite of TMC207(0 hour predose to 672 hours postdose, after each of the 3 single-dose administration)
- Number of Participants With Adverse Events(Up to 20 weeks)