An Open-label, Randomized, Four-period, Crossover Study in Two Panels of Healthy Adult Subjects to Assess the Relative Bioavailability, Food Effect, and Dose-dependence of Single-dose Immediate-release and Single-dose Dispersible Formulations of Pretomanid
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Relative Bioavailability - Cmax
研究概览
简要总结
This is a single-dose, open-label, randomized, four-period, four-treatment, crossover study in healthy adult subjects.
详细描述
This is a single-dose, open-label, randomized, four-period, four-treatment, crossover study in healthy adult subjects. Each panel of 24 subjects will be randomized according to the same 4-sequence, 4- period Williams design, in which each participant will receive four single-dose treatments. Subjects in Panel 1 will receive all treatments after consuming an FDA standard high-fat, high-calorie breakfast following an overnight fast of at least 10 hours. Subjects in Panel 2 will receive all treatments directly following an overnight fast of at least 10 hours. The two panels will be investigated concurrently.
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
- 19 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female. Females must not be pregnant or breastfeeding.
- •Willing and able to comply with the contraception requirements.
- •Between 19 and 50 years of age (inclusive) at the time of screening.
- •Body mass index (BMI) between 18.50 and 32 kg/m2 (inclusive) and weighs a minimum of 50 kg.
排除标准
- •History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
- •Vital signs at screening (measured sitting after a minimum 3 minutes rest) as follows: blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg or a heart rate lower than 40 bpm or higher than 99 bpm. Out-of-range vital signs may be repeated once.
- •History or presence of allergic or adverse response to pretomanid or related drugs.
- •Use of any drugs or treatment with any known drugs that are moderate or strong inducers or inhibitors of cytochrome P450 (CYP) enzymes (e.g., barbiturates, phenothiazines, cimetidine, carbamazepine) and/or P-gp, including St. John's Wort, within 30 days before the first dose of study medication, and that, in the Investigator's judgment, may impact subject safety or the validity of the study results.
- •Female with a positive pregnancy test result.
- •Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) at screening or has been previously treated for hepatitis B, hepatitis C, or HIV infection.
- •Hemoglobin <10.0 g/dL.
- •ALT (alanine transaminase) or AST (aspartate aminotransferase) >2.0 x the upper limit of normal (ULN).
- •Hyperbilirubinemia >1.5 x ULN.
- •History or presence of alcoholism or drug abuse within the past 2 years as determined by the Investigator to be clinically relevant.
- •Any clinically significant electrocardiogram abnormality at Screening (as deemed by decision of the Investigator and the Study Sponsor's Medical Monitor).
- •QTcF interval >450 msec for males or >470 msec for females at screening, Day -1, or Day 1 (pre-dose), or history of prolonged QT syndrome.
- •Family history of Long-QT Syndrome or sudden death without a preceding diagnosis of a condition that could be causative of sudden death (such as known coronary artery disease, congestive heart failure or terminal cancer).
研究组 & 干预措施
Panel 1: Pretomanid after meal
Each participant will receive four single-dose treatments with a 7-day washout period between each dose. Panel 1 will receive a meal before dosing.
干预措施: Pretomanid (Drug)
Panel 2: Pretomanid after fast
Each participant will receive four single-dose treatments with a 7-day washout period between each dose. Panel 2 will fast before dosing.
干预措施: Pretomanid (Drug)
结局指标
主要结局
Relative Bioavailability - Cmax
时间窗: intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose
Relative bioavailability will be determined separately for each panel using Cmax
Relative Bioavailability - AUC 0-t
时间窗: intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose
Relative bioavailability will be determined separately for each panel using AUC 0-t (area under the time vs concentration curve from time 0 to time t : h\*ng/mL)
Relative Bioavailability - AUC 0-inf
时间窗: intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose
Relative bioavailability will be determined separately for each panel using AUC 0-inf (area under the time vs concentration curve from time 0 to infinite time)
次要结局
- Food Effect - Ratio of Cmax Fed Vs Fasted(intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose)
- Food Effect - Ratio of AUC 0-t Fed Vs Fasted(intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose)
- Food Effect - Ratio of AUC 0-inf Fed Vs Fasted(intake (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose)
- Adverse Events - Overall Incidence(throughout the study, approximately 33 days)