An Adaptive, Part Open-label, Part Randomised Phase 1 Clinical Trial in Healthy Volunteers to Study Drug Interactions With RV521 Including Those Mediated by CYP3A4 and P-glycoprotein
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Effect of RV521 on Cmax of Midazolam
研究概览
简要总结
The purpose of this clinical trial is to learn about the interaction of sisunatovir with four medications (midazolam, itraconazole, rifampicin, and verapamil). These medications are known to have specific effects on enzymes and proteins that could influence drug absorption.
This study will be conducted in 4 Cohorts:
- Cohort 1 will receive midazolam and sisunatovir or placebo,
- Cohort 2 will receive Itraconazole and sisunatovir,
- Cohort 3 will receive verapamil and sisunatovir,
- Cohort 4 will receive rifampicin and sisunatovir. A placebo looks like sisunatovir but does not contain any active medicine in it.
This study is looking for health adult participants that meet the following criteria:
- Caucasians age 18 to 45 years
- All fertile participants must agree to the use of highly effective contraception
- Body mass index (BMI) of 18-25.0 kg/m2
- Male and female participants who are overtly healthy as determined by medical evaluation. This includes medical history, physical examination, blood pressure, pulse rate, standard 12-lead ECG (electrocardiogram), and laboratory tests.
This study consists of 2 parts, Part A and Part B. Part A will enroll up to 104 participants. The design of Part B will be determined after the completion of Part A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18 to 45 years, inclusive
- •Willing to comply with protocol defined contraception requirements
- •In good health with no history of major medical conditions
- •A body mass index (BMI) of 18 - 25 kg/m2
排除标准
- •Evidence of any clinically significant or currently active major medical condition
- •Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab)
- •Not willing to comply with protocol defined restrictions for intake of drugs of abuse, alcohol, nicotine-containing products, medication (prescription, OTC, herbal, vitamins/minerals etc) and specified food and drink products
研究组 & 干预措施
RV521 plus Itraconazole
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D7 plus Itraconazole 100 mg capsules for oral administration, a 200 mg dose administered once daily on D4 - D10, inclusive
干预措施: Itraconazole (Drug)
RV521 plus Itraconazole
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D7 plus Itraconazole 100 mg capsules for oral administration, a 200 mg dose administered once daily on D4 - D10, inclusive
干预措施: RV521 (Drug)
RV521 plus Verapamil
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D11 plus Verapamil, 80 mg tablets for oral administration, an 80 mg dose administered TDS daily on D4 - D14, inclusive
干预措施: Verapamil (Drug)
RV521 plus Verapamil
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D11 plus Verapamil, 80 mg tablets for oral administration, an 80 mg dose administered TDS daily on D4 - D14, inclusive
干预措施: RV521 (Drug)
RV521 plus Rifampicin
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D10 plus Rifadin, Rifampicin, 300 mg capsules for oral administration, a 600 mg dose administered once daily on D4 - D10, inclusive
干预措施: Rifampicin (Drug)
RV521 plus Rifampicin
RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D10 plus Rifadin, Rifampicin, 300 mg capsules for oral administration, a 600 mg dose administered once daily on D4 - D10, inclusive
干预措施: RV521 (Drug)
RV521 plus Midazolam
RV521 drug substance in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
干预措施: Midazolam (Drug)
RV521 plus Midazolam
RV521 drug substance in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
干预措施: RV521 (Drug)
Placebo plus Midazolam
Placebo for RV521 in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
干预措施: Midazolam (Drug)
Placebo plus Midazolam
Placebo for RV521 in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
干预措施: Placebo for RV521 (Drug)
结局指标
主要结局
Effect of RV521 on Cmax of Midazolam
时间窗: Baseline to study day 17
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on CL/F of Midazolam
时间窗: Baseline to study day 17
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on tmax of Midazolam
时间窗: Baseline to study day 17
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on t1/2 of Midazolam
时间窗: Baseline to study day 17
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on Cmax of RV521
时间窗: Baseline to study day 16
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on AUC of Midazolam
时间窗: Baseline to study day 17
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on Cmax of RV521
时间窗: Baseline to study day 12
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on tmax of RV521
时间窗: Baseline to study day 12
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on t1/2 of RV521
时间窗: Baseline to study day 12
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on CL/F of RV521
时间窗: Baseline to study day 12
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on tmax of RV521
时间窗: Baseline to study day 16
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on t1/2 of RV521
时间窗: Baseline to study day 16
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on AUC of RV521
时间窗: Baseline to study day 16
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on CL/F of RV521
时间窗: Baseline to study day 16
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on AUC of RV521
时间窗: Baseline to study day 12
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on Cmax of RV521
时间窗: Baseline to study day 15
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on tmax of RV521
时间窗: Baseline to study day 15
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on t1/2 of RV521
时间窗: Baseline to study day 15
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on CL/F of RV521
时间窗: Baseline to study day 15
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on AUC of RV521
时间窗: Baseline to study day 15
The specified pharmacokinetic parameter will be summarised using descriptive statistics
次要结局
- Number of subjects with treatment-related adverse events as assessed by NCI CTCAE V5.0(Screening to final study visit (performed at 7 days following the last dose of any intervention))
- Number of subjects with QT/QTc interval changes relative to baseline who received RV521 (monotherapy), Midazolam (monotherapy) or RV521 and Midazolam (combination therapy)(Baseline to to final study visit (performed at 7 days following the last dose of any intervention))