A Study to Learn About the Drug-drug Interactions of Sisunatovir in Healthy Adult Participants
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
3 other identifiers
interventional
82
1 country
1
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:
- 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2018
Shorter than P25 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 7, 2018
CompletedFirst Submitted
Initial submission to the registry
December 5, 2018
CompletedFirst Posted
Study publicly available on registry
December 20, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 17, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
March 17, 2019
CompletedApril 22, 2024
April 1, 2024
4 months
December 5, 2018
April 18, 2024
Conditions
Outcome Measures
Primary Outcomes (20)
Effect of RV521 on Cmax of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 17
Effect of RV521 on tmax of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 17
Effect of RV521 on t1/2 of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 17
Effect of RV521 on AUC of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 17
Effect of RV521 on CL/F of Midazolam
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 17
Effect of itraconazole on Cmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 12
Effect of itraconazole on tmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 12
Effect of itraconazole on t1/2 of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 12
Effect of itraconazole on AUC of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 12
Effect of itraconazole on CL/F of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 12
Effect of verapamil on Cmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 16
Effect of verapamil on tmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 16
Effect of verapamil on t1/2 of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 16
Effect of verapamil on AUC of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 16
Effect of verapamil on CL/F of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 16
Effect of rifampicin on Cmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 15
Effect of rifampicin on tmax of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 15
Effect of rifampicin on t1/2 of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 15
Effect of rifampicin on AUC of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 15
Effect of rifampicin on CL/F of RV521
The specified pharmacokinetic parameter will be summarised using descriptive statistics
Baseline to study day 15
Secondary Outcomes (2)
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)
Study Arms (5)
RV521 plus Itraconazole
EXPERIMENTALRV521 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
RV521 plus Verapamil
EXPERIMENTALRV521 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
RV521 plus Rifampicin
EXPERIMENTALRV521 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
RV521 plus Midazolam
EXPERIMENTALRV521 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
Placebo plus Midazolam
PLACEBO COMPARATORPlacebo 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
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (1)
Richmond Pharmacology Ltd
London, SE1 1YR, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 5, 2018
First Posted
December 20, 2018
Study Start
November 7, 2018
Primary Completion
March 17, 2019
Study Completion
March 17, 2019
Last Updated
April 22, 2024
Record last verified: 2024-04
Data Sharing
- IPD Sharing
- Will not share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.