A Study to Explore the Pharmacokinetics of Rilpivirine With Rifabutin in Healthy Participants

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Rilpivirine; Drug: Rifabutin

• Registration Number: NCT01615614
• Lead Sponsor: Janssen R&D Ireland

Brief Summary

The purpose of this study is to explore the pharmacokinetics of different dosing regimens of rilpivirine in combination with rifabutin in healthy participants.

Detailed Description

This is a Phase I, open-label (the participant will know the identity of the treatment they receive), 3-period study to investigate the pharmacokinetic (what the body does to the medication) interaction of steady-state (constant concentrations in your blood resulting from a fixed dosing regimen) rilpivirine and steady-state rifabutin. Twenty healthy participants will be enrolled and will receive 3 different treatments (treatment A: rilpivirine 25 mg once daily administered daily for 11 days; treatment B: rilpivirine 50 mg once daily administered for 11 days + rifabutin 300 mg daily administered for 17 days; treatment C: rilpivirine (in a regimen to be determined based on an interim analysis of treatments A and B) administered for 11 days + rifabutin 300 mg daily administered for 17 days). All 20 participants will be randomized (the study drug is assigned by chance) to receive treatments A (10 participants) and treatment B (10 participants) and there will be a washout period of at least 21 days between treatments A and B. After all participants have completed treatments A and B, there will be an interim analysis to decide upon the dosing regimen for rilpivirine in treatment C (the rilpivirine regimen in treatment C could be either once daily or twice daily with a total daily dose of rilpivirine between 25 and 75 mg). All 20 participants will receive treatment C. Safety and tolerability will be evaluated throughout the study.

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2012-06-06
• Study First Submitted QC: 2012-06-07
• Study First Posted: 2012-06-08
• Primary Completion: 2012-09
• Study Completion: 2012-09
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-27
• Last Update Posted: 2014-03-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Participants should be healthy on the basis of physical examination, medical history, vital signs, electrocardiogram, and the results of blood biochemistry and hematology tests and a urinalysis performed at screening
• Men must agree to use a highly effective method of birth control (ie, male condom with either female intrauterine device, diaphragm, cervical cap or hormone based contraceptives by their female partner), and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
• Women must be postmenopausal for at least 2 years, or be surgically sterile (have had a total hysterectomy or bilateral oophorectomy, tubal ligation/bilateral tubal clips without reversal operation, or otherwise be incapable of becoming pregnant)
• Women must have a negative pregnancy test at screening
• Participants must be non-smoking for at least 3 months prior to screening

Exclusion Criteria

• A positive HIV-1 or HIV-2 test at screening
• History or suspicion of alcohol or barbiturate, amphetamine, recreational or narcotic drug use which in the Investigator's opinion would compromise subject safety and/or compliance with study procedures
• Hepatitis A, B or C infection (confirmed by hepatitis A IgM, HBsAg, or hepatitis C virus antibody, respectively) at screening
• Currently active clinically significant gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, endocrine, renal, hepatic, respiratory, inflammatory or infectious disease
• Any history of tuberculosis, ocular herpes, or uveitis
• Currently significant diarrhea or gastric stasis that in the Investigator's opinion could influence drug absorption or bioavailability

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment B	Rilpivirine	Rilpivirine 50 mg once daily will be administered for 11 days and rifabutin 300 mg once daily will be administered for 17 days
Treatment B	Rifabutin	Rilpivirine 50 mg once daily will be administered for 11 days and rifabutin 300 mg once daily will be administered for 17 days
Treatment A	Rilpivirine	Rilpivirine 25 mg once daily will be administered for 11 days
Treatment C	Rilpivirine	Rilpivirine (in a regimen to be determined based on an interim pharmacokinetic analysis of treatment A and B) will be administered for 11 days and rifabutin 300 mg once daily will be administered for 17 days.
Treatment C	Rifabutin	Rilpivirine (in a regimen to be determined based on an interim pharmacokinetic analysis of treatment A and B) will be administered for 11 days and rifabutin 300 mg once daily will be administered for 17 days.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of different dosing regimens of rilpivirine in combination with rifabutin, at steady-state	Up to 168 hours (postdose)	Pharmacokinetics of different dosing regimens of rilpivirine in combination with rifabutin, at steady-state will be evaluated.

Secondary Outcome Measures

Name	Time	Method
Number of participants with adverse events as a measure of safety and tolerability	Up to 87 days	Number of participants with adverse events will be evaluated to assess safety and tolerability.