Clinical trial NCT03782662: A Study to Learn About the Drug-drug Interactions of Sisunatovir in Healthy Adult Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Respiratory Syncytial Virus Infections
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-12-20
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Effect of RV521 on Cmax of Midazolam
timeFrame: Baseline to study day 17
measure: Effect of RV521 on tmax of Midazolam
timeFrame: Baseline to study day 17
measure: Effect of RV521 on t1/2 of Midazolam
timeFrame: Baseline to study day 17
measure: Effect of RV521 on AUC of Midazolam
timeFrame: Baseline to study day 17
measure: Effect of RV521 on CL/F of Midazolam
timeFrame: Baseline to study day 17
measure: Effect of itraconazole on Cmax of RV521
timeFrame: Baseline to study day 12
measure: Effect of itraconazole on tmax of RV521
timeFrame: Baseline to study day 12
measure: Effect of itraconazole on t1/2 of RV521
timeFrame: Baseline to study day 12
measure: Effect of itraconazole on AUC of RV521
timeFrame: Baseline to study day 12
measure: Effect of itraconazole on CL/F of RV521
timeFrame: Baseline to study day 12
measure: Effect of verapamil on Cmax of RV521
timeFrame: Baseline to study day 16
measure: Effect of verapamil on tmax of RV521
timeFrame: Baseline to study day 16
measure: Effect of verapamil on t1/2 of RV521
timeFrame: Baseline to study day 16
measure: Effect of verapamil on AUC of RV521
timeFrame: Baseline to study day 16
measure: Effect of verapamil on CL/F of RV521
timeFrame: Baseline to study day 16
measure: Effect of rifampicin on Cmax of RV521
timeFrame: Baseline to study day 15
measure: Effect of rifampicin on tmax of RV521
timeFrame: Baseline to study day 15
measure: Effect of rifampicin on t1/2 of RV521
timeFrame: Baseline to study day 15
measure: Effect of rifampicin on AUC of RV521
timeFrame: Baseline to study day 15
measure: Effect of rifampicin on CL/F of RV521
timeFrame: Baseline to study day 15
Secondary outcomes:
measure: Number of subjects with treatment-related adverse events as assessed by NCI CTCAE V5.0
timeFrame: Screening to final study visit (performed at 7 days following the last dose of any intervention)
measure: Number of subjects with QT/QTc interval changes relative to baseline who received RV521 (monotherapy), Midazolam (monotherapy) or RV521 and Midazolam (combination therapy)
timeFrame: Baseline to to final study visit (performed at 7 days following the last dose of any intervention)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Richmond Pharmacology Ltd
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: