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: 1. Caucasians age 18 to 45 years 2. All fertile participants must agree to the use of highly effective contraception 3. Body mass index (BMI) of 18-25.0 kg/m2 4. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
82
Itraconazole capsules
Verapamil tablets
Rifampicin capsules
Midazolam oromucosal solution
Placebo for RV521 capsules
RV521 capsules
Richmond Pharmacology Ltd
London, United Kingdom
Effect of RV521 on Cmax of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 17
Effect of RV521 on tmax of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 17
Effect of RV521 on t1/2 of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 17
Effect of RV521 on AUC of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 17
Effect of RV521 on CL/F of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 17
Effect of itraconazole on Cmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 12
Effect of itraconazole on tmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 12
Effect of itraconazole on t1/2 of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 12
Effect of itraconazole on AUC of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 12
Effect of itraconazole on CL/F of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 12
Effect of verapamil on Cmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 16
Effect of verapamil on tmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 16
Effect of verapamil on t1/2 of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 16
Effect of verapamil on AUC of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 16
Effect of verapamil on CL/F of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 16
Effect of rifampicin on Cmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 15
Effect of rifampicin on tmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 15
Effect of rifampicin on t1/2 of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 15
Effect of rifampicin on AUC of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 15
Effect of rifampicin on CL/F of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Time frame: Baseline to study day 15
Number of subjects with treatment-related adverse events as assessed by NCI CTCAE V5.0
The number of subjects with treatment-related adverse events will be summarised by treatment group using descriptive statistics
Time frame: 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)
Descriptive statistics will be given by time point and dose-group for absolute values and change from baseline. Results will be tabulated and for QTc, the difference to time matched placebo will also be displayed
Time frame: Baseline to to final study visit (performed at 7 days following the last dose of any intervention)
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