A Study to Learn About the Drug-drug Interactions of Sisunatovir in Healthy Adult Participants

Respiratory Syncytial Virus Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03782662
• Other study ID #: REVC004
• Secondary ID: C52410042018-003
• Status: Completed
• Phase: Phase 1
• Start date: November 7, 2018
• Est. completion date: March 17, 2019

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: March 17, 2019
• Est. primary completion date: March 17, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Respiratory Syncytial Virus Infections

Intervention

Drug:
• Itraconazole
Itraconazole capsules
• Verapamil
Verapamil tablets
• Rifampicin
Rifampicin capsules
• Midazolam
Midazolam oromucosal solution
• Placebo for RV521
Placebo for RV521 capsules
• RV521
RV521 capsules

Locations

Country	Name	City	State
United Kingdom	Richmond Pharmacology Ltd	London

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of RV521 on Cmax of Midazolam	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 17
Primary	Effect of RV521 on tmax of Midazolam	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 17
Primary	Effect of RV521 on t1/2 of Midazolam	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 17
Primary	Effect of RV521 on AUC of Midazolam	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 17
Primary	Effect of RV521 on CL/F of Midazolam	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 17
Primary	Effect of itraconazole on Cmax of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 12
Primary	Effect of itraconazole on tmax of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 12
Primary	Effect of itraconazole on t1/2 of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 12
Primary	Effect of itraconazole on AUC of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 12
Primary	Effect of itraconazole on CL/F of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 12
Primary	Effect of verapamil on Cmax of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 16
Primary	Effect of verapamil on tmax of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 16
Primary	Effect of verapamil on t1/2 of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 16
Primary	Effect of verapamil on AUC of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 16
Primary	Effect of verapamil on CL/F of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 16
Primary	Effect of rifampicin on Cmax of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 15
Primary	Effect of rifampicin on tmax of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 15
Primary	Effect of rifampicin on t1/2 of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 15
Primary	Effect of rifampicin on AUC of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 15
Primary	Effect of rifampicin on CL/F of RV521	The specified pharmacokinetic parameter will be summarised using descriptive statistics	Baseline to study day 15
Secondary	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	Screening to final study visit (performed at 7 days following the last dose of any intervention)
Secondary	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	Baseline to to final study visit (performed at 7 days following the last dose of any intervention)

External Links

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