A Phase 1, Open-label, Randomized, Crossover Study to Assess the Drug-Drug Interaction Between Bedaquiline and Clarithromycin in Healthy Adult Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Maximum Observed Analyte Concentration (Cmax) of Bedaquiline and its Metabolite (M2)
研究概览
简要总结
The purpose of this study is to assess the effect of steady-state clarithromycin once every 12 hour on the pharmacokinetic parameters of bedaquiline and its active metabolite M2 after a single dose of bedaquiline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 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
- •A female participant must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at screening and on Day -1 in each treatment period
- •Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
- •A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 90 days after receiving the last dose of bedaquiline
- •During the study and for a minimum of at least 90 days after receiving the last dose of bedaquiline: a) A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak. b) A male participant must agree not to donate sperm for the purpose of reproduction
- •Body mass index (BMI between 18.0 and 30.0 kilogram (kg) per meter square (inclusive), and body weight not less than 50 kg at screening
排除标准
- •Participant has history or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease (including bronchospastic respiratory disease), diabetes mellitus, hepatic or renal insufficiency (for example, estimated creatinine clearance below 60 milliliter per minute [mL/min] at screening), gastrointestinal disease (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- •Participant with a past history of heart arrhythmias (extrasystoles or tachycardia at rest), or history of risk factors for Torsade de Pointes syndrome (for example, hypokalemia, or family history of long QT syndrome). Family history of sudden unexplained death (including sudden infant death syndrome in a first-degree relative (that is, sibling, offspring, or biological parent). Ongoing bradyarrhythmias or ongoing hypothyroidism (confirmed by elevated thyroid-stimulating hormone [TSH] level)
- •Participant with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
- •Participant has taken any disallowed therapies before the planned first intake of study drug
- •Participant has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) criteria within 5 years before screening or positive test result(s) for alcohol and/or drugs of abuse (including barbiturates, opiates, cocaine, amphetamines, methadone, benzodiazepines, methamphetamine, tetrahydrocannabinol, phencyclidine, and tricyclic antidepressants) at screening and on Day 1 of each treatment period
研究组 & 干预措施
Treatment Sequence 1: Bedaquiline and Clarithromycin
Participants will receive bedaquiline on Day 1 in Period 1, followed by clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 2. There will be washout period of at least 28 days starting on Day 1.
干预措施: Bedaquiline (Drug)
Treatment Sequence 1: Bedaquiline and Clarithromycin
Participants will receive bedaquiline on Day 1 in Period 1, followed by clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 2. There will be washout period of at least 28 days starting on Day 1.
干预措施: Clarithromycin (Drug)
Treatment Sequence 2: Clarithromycin and Bedaquiline
Participants will receive clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 1, followed by bedaquiline on Day 1 in Period 2. There will be a washout period of at least 28 days starting after bedaquiline administration on Day 5.
干预措施: Bedaquiline (Drug)
Treatment Sequence 2: Clarithromycin and Bedaquiline
Participants will receive clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 1, followed by bedaquiline on Day 1 in Period 2. There will be a washout period of at least 28 days starting after bedaquiline administration on Day 5.
干预措施: Clarithromycin (Drug)
结局指标
主要结局
Maximum Observed Analyte Concentration (Cmax) of Bedaquiline and its Metabolite (M2)
时间窗: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose
Cmax is the maximum observed analyte concentration.
Minimum Observed Analyte Concentration (Cmin) of Bedaquiline and its Metabolite (M2)
时间窗: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose
Cmin is the minimum observed analyte concentration.
Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 72 Hours Post Dosing (AUC72h) of Bedaquiline and its Metabolite (M2)
时间窗: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours Post-dose
AUC72h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 72 hours post dosing, calculated by linear-linear trapezoidal summation.
Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 240 Hours Post Dosing (AUC240h) of Bedaquiline and its Metabolite (M2)
时间窗: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, and 240 hours Post-dose
AUC240h is the area under the analyte concentration-time curve from time 0 to 240 hours, calculated by linear-linear trapezoidal summation.
次要结局
- Time to Reach Maximum Observed Analyte Concentration (Tmax) of Clarithromycin and its Metabolite 14-OH-Clarithromycin(Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose)
- Cmin of Clarithromycin and its Metabolite 14-OH-Clarithromycin(Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(Up to 90 days)
- Cmax of Clarithromycin and its Metabolite 14-OH-Clarithromycin(Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose)
- Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 12 Hours Post Dosing (AUC12h) of Clarithromycin and its Metabolite 14-OH-Clarithromycin(Pre-dose, 1, 2, 3, 4, 5, 6, 8, and 12 hours Post-dose)