A Phase I, Open-label, Randomized, 3-way Crossover Study in 3 Panels of Healthy, Adult Subjects to Assess the Relative Bioavailability of TMC207 Following Single-dose Administration of Two Pediatric Formulations Using a 100 mg Tablet Formulation as the Reference, With and Without Food.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 主要终点
- Plasma concentrations of TMC207
研究概览
简要总结
The purpose of this study is to test the relative bioavailability (extent and rate to which a drug is taken up by the body) of TMC207 following the administration of two pediatric formulations of TMC207 taken with and without food in healthy adult participants.
详细描述
This is an open-label (all study staff and participants know the identity of treatments assigned), 3-way cross-over (method used to switch participants from one treatment to another treatment) study. Three panels of 12 healthy adult participants each will be enrolled. Within each panel, participants will be randomly (by chance) assigned to 1 of 6 treatment sequences to receive each of the 3 formulations of TMC207 in a randomized order. The 3 formulations of TMC207 will be referred to as Treatments A, B, and C. In Treatment A, participants will receive a single 100-mg dose of TMC207 formulated as a 100-mg tablet (reference formulation). In Treatment B, participants will receive a single 100-mg dose of TMC207 formulated as 20-mg water dispersible (dissolvable) tablets (i.e. 5 tablets) (pediatric formulation 1). In Treatment C, participants will receive a single 100-mg dose of TMC207 formulated as granules 5 grams (20 mg/g) (pediatric formulation 2). Each treatment will be separated by 4 weeks. Participants in Panel 1 will receive each treatment with a standardized breakfast, Panel 2 will receive each treatment with yogurt, and Panel 3 will receive each treatment after a 10-hour overnight fast (without food). The duration of the treatment period in this study will be 8.5 weeks (includes 4 weeks between treatments).
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
- •Healthy participant on the basis of physical examination, medical history, vital signs, and electrocardiogram (ECG), and the results of blood biochemistry and hematology tests and a urinalysis performed at screening
- •Must 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
- •Women must be postmenopausal for at least 2 years and have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1
- •Men must agree to use a highly effective method of birth control (eg., male condom with either female intrauterine device, diaphragm, cervical cap or hormone based contraceptives by their female partner) when having sexual intercourse with a female partner of childbearing potential, and to not donate sperm during the study and for 6 months after receiving the last dose of study drug. Men who have had a vasectomy and have a female partner of childbearing potential must agree to use a male condom during the study and for 6 months after receiving the last dose of study drug
- •Participants must be non-smokers for at least 3 months prior to screening
排除标准
- •Human immunodeficiency virus - type 1 (HIV-1) or type 2 (HIV-2) infection confirmed at screening
- •Hepatitis A, B or C infection confirmed at screening
- •A positive urine drug test or alcohol breath test at screening. Urine will be tested for the presence of amphetamines, barbiturates, benzodiazepines, cocaine, methadone, and opioids
- •History or any currently active disease or condition that the Investigator considers to be clinically significant for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
研究组 & 干预措施
Treatment Sequence ABC
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment A (reference) (Drug)
Treatment Sequence ABC
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment B (Drug)
Treatment Sequence ABC
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment C (Drug)
Treatment Sequence ACB
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment A (reference) (Drug)
Treatment Sequence ACB
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment B (Drug)
Treatment Sequence ACB
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment C (Drug)
Treatment Sequence BAC
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment A (reference) (Drug)
Treatment Sequence BAC
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment B (Drug)
Treatment Sequence BAC
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment C (Drug)
Treatment Sequence BCA
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment A (reference) (Drug)
Treatment Sequence BCA
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment B (Drug)
Treatment Sequence BCA
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment C (Drug)
Treatment Sequence CBA
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment A (reference) (Drug)
Treatment Sequence CBA
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment B (Drug)
Treatment Sequence CBA
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment C (Drug)
Treatment Sequence CAB
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment A (reference) (Drug)
Treatment Sequence CAB
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment B (Drug)
Treatment Sequence CAB
Participants in Panel 1 will take the sequence of 3 treatments with a standardized breakfast, participants in Panel 2 will take the sequence of 3 treatments with yogurt, and participants in Panel 3 will take the sequence of 3 treatments after a 10-hour overnight fast (without food). Each treatment in each treatment sequence to be separated by 4 weeks.
干预措施: Treatment C (Drug)
结局指标
主要结局
Plasma concentrations of TMC207
时间窗: Up to 72 hours after study drug intake during 3 treatment sessions
Protocol-specified pharmacokinetic parameters will be determined from plasma samples collected after each administration of study drug to assess the relative bioavailability of TMC207.
次要结局
- The plasma concentration of the primary metabolite in TMC207(Up to 72 hours after each study drug intake during 3 treatment sessions)
- The effect of food on the relative bioavailability of TMC207(Up to 72 hours after study drug intake during 3 treatment sessions)
- The number of participants reporting adverse events as a measure of safety and tolerability(Up to approximately 12.5 weeks)
- The taste of TMC207(On Day 1 after study drug administration during 3 treatment sessions.)