Respiratory Syncytial Virus Infections
Conditions
Brief summary
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.
Interventions
DRUGVerapamil
Verapamil tablets
DRUGItraconazole
Itraconazole capsules
DRUGRifampicin
Rifampicin capsules
DRUGMidazolam
Midazolam oromucosal solution
DRUGPlacebo for RV521
Placebo for RV521 capsules
DRUGRV521
RV521 capsules
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of rifampicin on CL/F of RV521 | Baseline to study day 15 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of rifampicin on t1/2 of RV521 | Baseline to study day 15 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of rifampicin on AUC of RV521 | Baseline to study day 15 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of RV521 on Cmax of Midazolam | Baseline to study day 17 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of RV521 on tmax of Midazolam | Baseline to study day 17 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of RV521 on t1/2 of Midazolam | Baseline to study day 17 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of RV521 on AUC of Midazolam | Baseline to study day 17 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of RV521 on CL/F of Midazolam | Baseline to study day 17 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of itraconazole on Cmax of RV521 | Baseline to study day 12 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of itraconazole on tmax of RV521 | Baseline to study day 12 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of itraconazole on t1/2 of RV521 | Baseline to study day 12 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of itraconazole on AUC of RV521 | Baseline to study day 12 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of itraconazole on CL/F of RV521 | Baseline to study day 12 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of verapamil on Cmax of RV521 | Baseline to study day 16 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of verapamil on tmax of RV521 | Baseline to study day 16 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of verapamil on t1/2 of RV521 | Baseline to study day 16 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of verapamil on AUC of RV521 | Baseline to study day 16 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of verapamil on CL/F of RV521 | Baseline to study day 16 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of rifampicin on Cmax of RV521 | Baseline to study day 15 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
| Effect of rifampicin on tmax of RV521 | Baseline to study day 15 | The specified pharmacokinetic parameter will be summarised using descriptive statistics |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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 |
| 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) | The number of subjects with treatment-related adverse events will be summarised by treatment group using descriptive statistics |
Countries
United Kingdom
Outcome results
None listed