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

A Phase I, Open-Label Study in Healthy Subjects, to Explore the Pharmacokinetics of Different Dosing Regimens of Rilpivirine in Combination With Rifabutin, at Steady-State

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rilpivirine; Drug: Rifabutin

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Rilpivirine 25 mg once daily will be administered for 11 days	Drug: Rilpivirine; Type=exact number, unit=mg, number=25, 50, and will be determined after treatment A and B analysis form=tablet, route=oral. Once or twice daily with a total daily dose of rilpivirine between 25 and 75 mg will be administered for 11 days.
Experimental: Treatment B; Rilpivirine 50 mg once daily will be administered for 11 days and rifabutin 300 mg once daily will be administered for 17 days	Drug: Rilpivirine; Type=exact number, unit=mg, number=25, 50, and will be determined after treatment A and B analysis form=tablet, route=oral. Once or twice daily with a total daily dose of rilpivirine between 25 and 75 mg will be administered for 11 days.; Drug: Rifabutin; Type=exact number, unit=mg, number=150, form=capsule, route=oral. Two capsules daily will be administered for 17 days.
Experimental: Treatment C; 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.	Drug: Rilpivirine; Type=exact number, unit=mg, number=25, 50, and will be determined after treatment A and B analysis form=tablet, route=oral. Once or twice daily with a total daily dose of rilpivirine between 25 and 75 mg will be administered for 11 days.; Drug: Rifabutin; Type=exact number, unit=mg, number=150, form=capsule, route=oral. Two capsules daily will be administered for 17 days.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	Number of participants with adverse events will be evaluated to assess safety and tolerability.	Up to 87 days

Collaborators and Investigators

• Sponsor: Janssen R&D Ireland

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 6, 2012
• First Submitted That Met QC Criteria: June 7, 2012
• First Posted (Estimate): June 8, 2012

Study Record Updates

• Last Update Posted (Estimate): March 28, 2014
• Last Update Submitted That Met QC Criteria: March 27, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy participants; Rilpivirine; Rifabutin
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Anti-Bacterial Agents; Antitubercular Agents; Antibiotics, Antitubercular; Rifabutin; Rilpivirine
• Other Study ID Numbers: CR100812; TMC278IFD1003 (Other Identifier: Janssen R&D Ireland); 2012-000141-12 (EudraCT Number)