TMC207-TiDP13-C117: Interaction Study in Human Immunodeficiency Virus-type 1 (HIV-1) Infected Patients With Nevirapine (NVP)

April 1, 2014 updated by: Tibotec BVBA

A Phase I, Open-label, Single-sequence Drug-drug Interaction Trial to Investigate the Pharmacokinetic Interaction Between Steady-state Nevirapine and Single-dose TMC207 in HIV-1 Infected Subjects.

The purpose of this Phase I, open-label, single sequence drug-drug interaction trial in human immunodeficiency virus-type 1 infected patients is to investigate the potential interaction between steady-state nevirapine (NVP) 200 mg b.i.d. (twice a day) and a single dose of 400 mg TMC207 and to explore the pharmacokinetics (how the drug is absorbed into the bloodstream, distributed in the body and eliminated from the body).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

TMC207 is being investigated for the treatment of M. tuberculosis (TB) infection. This is a Phase I, open-label (both participant and investigator know the name of the assigned medication), single-sequence (all participants receive treatments in the same order) drug-drug interaction trial in human immunodeficiency virus - type 1 (HIV-1) infected patients to investigate the potential interaction between steady-state nevirapine (NVP) 200 mg b.i.d. (twice a day) and a single dose of 400 mg TMC207. The study medication will be taken orally. The trial population will consist of 16 patients infected with HIV-1 virus who have not yet been treated for this infection (antiretroviral or ARV naïve) with a medical indication to start ARV therapy and electing to start treatment with NVP plus two nucleos(t)ide reverse transcriptase inhibitors (N(t)RTIs). The primary objective is to evaluate the effect of steady-state NVP 200 mg b.i.d. on the pharmacokinetics of TMC207 and its M2 metabolite after single-dose administration of TMC207 400 mg, in HIV-1 infected patients. The secondary objectives are to evaluate the effect of single-dose TMC207 400 mg on the steady-state plasma concentrations of NVP 200 mg b.i.d. and to evaluate the short-term safety and tolerability of coadministration of single-dose TMC207 and steady-state NVP in HIV-1 infected patients. Prior to starting the NVP-containing regimen, patients will receive a single dose of TMC207 400 mg (Treatment A). At least 2 but no more than 4 weeks later, NVP will be started (in combination with 2 N(t)RTIs) at the recommended dosing regimen (200 mg once daily for 2 weeks followed by 200 mg twice daily). After 4 weeks of NVP at a dose of 200 mg b.i.d., a second single dose of TMC207 400 mg will be administered (Treatment B).Pharmacokinetic profiles over 336 hours will be determined for TMC207 and its N-monodesmethyl metabolite (M2) after administration of TMC207 400 mg alone, and in combination with steady-state NVP. Morning predose concentrations of NVP will be determined at several time points.Safety and tolerability will be evaluated throughout the trial. Adverse events will be recorded at every visit. A blood and urine sample will be taken at screening, day -1, 1, 2 and 15 of treatment A and B and at both follow-up visits. An electrocardiogram will be recorded at screening, twice on day 1 and once on day 2 and 15 of treatment A and B and at the last follow-up visit. Vital signs will be measured at screening, on day 1, 2 and 15 of treatment A and B and at both follow-up visits. A physical examination will be performed at screening, on day -1 of treatment A and B and at both follow-up visits. On day 1 of treatment A and B 400 mg TMC207 (4 tablets) will be taken by mouth in the morning within 10 minutes after completion of the breakfast. At least 2 but no more than 4 weeks after the first single dose of TMC207, NVP will be started [in combination with 2 N(t)RTIs] as 200 mg once daily for 2 weeks followed by 200 mg twice daily, orally. After 4 weeks of NVP at a dose of 200 mg twice daily, a second single dose of TMC207 will be administered.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Documented HIV-1 infection
  • Antiretroviral naïve patients, for whom in the judgment of the investigator, it is appropriate to initiate NVP-containing ARV therapy at least 2 but no more than 4 weeks after the first dose of TMC207, based on the patient's medical condition and taking into account local treatment guidelines for the treatment of HIV-1 infection
  • Patient agrees not to start ARV therapy until at least 2 weeks after the first dose of TMC207
  • patient agrees not to change NVP and N(t)RTI therapy (including dosages) from the start of NVP treatment at 200 mg b.i.d. until Day 15 of Treatment B, unless this is medically indicated as decided by the treating physician.

Exclusion Criteria:

  • Female, except if postmenopausal since more than 2 years, or posthysterectomy, or post-surgical sterilization
  • Patient has any currently active AIDS defining illness
  • Active tuberculosis
  • Known or suspected acute HIV-1 infection
  • Currently active or underlying gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, or respiratory disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TMC207, nevirapine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary objective is to evaluate the effect of steady-state NVP 200 mg twice daily on the pharmacokinetics of TMC207 and its M2 metabolite after single-dose administration of TMC207 400 mg, in HIV-1 infected patients
Time Frame: Pharmacokinetic profiles over 336 hours will be determined for TMC207 and its N-monodesmethyl metabolite (M2) after administration of TMC207 400 mg alone, and in combination with steady-state NVP.
Pharmacokinetic profiles over 336 hours will be determined for TMC207 and its N-monodesmethyl metabolite (M2) after administration of TMC207 400 mg alone, and in combination with steady-state NVP.

Secondary Outcome Measures

Outcome Measure
Time Frame
The effect of single-dose TMC207 on the steady-state plasma concentrations of NVP will be evaluated.
Time Frame: This will be determined during 18 days in treatment B
This will be determined during 18 days in treatment B
The short-term safety and tolerability of coadministration of single-dose TMC207 and steady-state NVP will be evaluated in HIV-1 infected patients.
Time Frame: This will be determined during 15 days in treatment B
This will be determined during 15 days in treatment B

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

June 1, 2010

Study Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

May 7, 2009

First Submitted That Met QC Criteria

May 28, 2009

First Posted (Estimate)

June 1, 2009

Study Record Updates

Last Update Posted (Estimate)

April 2, 2014

Last Update Submitted That Met QC Criteria

April 1, 2014

Last Verified

April 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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