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

Pfizer

Status and phase: Completed; Phase 1

Conditions: Respiratory Syncytial Virus Infections

Treatments: Drug: Midazolam; Drug: Rifampicin; Drug: RV521; Drug: Verapamil; Drug: Itraconazole; Drug: Placebo for RV521

Study type: Interventional

Funder types: Industry

Identifiers

NCT03782662

REVC004

2018-003256-21 (EudraCT Number)

C5241004 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 82 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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82 participants in 5 patient groups, including a placebo group

RV521 plus Itraconazole

Experimental group

Description:

RV521 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

Treatment:

Drug: RV521

Drug: Itraconazole

RV521 plus Verapamil

Experimental group

Description:

RV521 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

Treatment:

Drug: RV521

Drug: Verapamil

RV521 plus Rifampicin

Experimental group

Description:

RV521 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

Treatment:

Drug: RV521

Drug: Rifampicin

RV521 plus Midazolam

Experimental group

Description:

RV521 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

Treatment:

Drug: RV521

Drug: Midazolam

Placebo plus Midazolam

Placebo Comparator group

Description:

Placebo 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

Treatment:

Drug: Midazolam

Drug: Placebo for RV521