TMC435-TiDP16-C110: Evaluation of the (Possible) Influence of TMC435 on the Blood Levels of Methadone (and the Other Way Around), When TMC435 is Being Co-administerd to Study Participants Who Are Currently Being Treated With a Stable Dose of Methadone as Maintenance Therapy.

Condition(s) targeted: Hepatitis C; Hepacivirus

Intervention: TMC435 (Drug)

Phase: Phase 1

Status: Not yet recruiting

Sponsored by: Tibotec Pharmaceuticals, Ireland

Official(s) and/or principal investigator(s):
Tibotec Pharmaceuticals Limited Clinical Trial, Study Director, Affiliation: Tibotec Pharmaceutical Limited

Overall contact:
This study is not yet recruiting patients. Please check back for future recruiting sites, or email, Email: info1@veritasmedicine.com

The purpose of this study is to investigate whether and how intake of TMC435 influences the levels of methadone in the body when TMC435 is taken during methadone therapy. TMC435 is currently under development for Hepatitis C (HCV). A substantial percentage of HCV patients are former drug users, and are on methadone maintenance therapy. In this study, 12 HCV-negative methadone users will be enrolled. During the study, blood samples will be drawn to compare the blood levels of TMC435 of the study participants on stable maintenance methadone therapy with blood levels of TMC435 in volunteers who were treated with TMC435 only (historical data). Participants will also be asked to complete specific questionnaires in order to determine any clinical reaction of the body (also called symptoms) on a reduction or an increase of methadone concentrations in their blood. On predefined time points, the diameter of the pupils will be measured as well, which is a non-invasive method to detect too high or too low levels of methadone in the blood. The safety and tolerability of the coadministration (methadone + TMC435) will also be assessed. This study has manly been set-up in order to verify wheher the dose of methadone needs to be adjusted when being combined with TMC435 intake and vice versa.

Official title: A Phase I, Open-label, Single-sequence Drug-drug Interaction Trial in Subjects on Stable Methadone Maintenance Therapy, to Investigate the Potential Pharmacokinetic Interaction Between TMC435 and Methadone, at Steady State.

Study design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Pharmacokinetics/Dynamics Study

Primary outcome: Pharmacokinetic parameters of R- and S-methadone will be assessed.

Secondary outcome:

Pharmacodynamic responses based on questionnaires and pupilometry will be assessed

Pharmacokinetic parameters of TMC435 will be assessed

Short-term safety and tolerability will be assessed

Detailed description: This is an open label (all parties, including the sponsor, study doctor and volunteer know the treatment per volunteer) drug-drug interaction (TMC435 versus methadone) study in volunteers who are on a stable methadone therapy, to investigate the potential interaction between TMC435 (150 mg, once a day) and methadone (the maintenance dose may differ from volunteer to volunteer, but will range from 30 to 130 mg, once a day). Each volunteer needs to be on a stable methadone therapy for at least 30 days before screening. As of 14 days before the first intake of TMC435, the daily intake of methadone will be witnessed by medical staff. Intake of TMC435 starts at Day 1 and finishes at Day 7. In the mean time, treatment with methadone will continue unchanged. On Day-1 (i. e. the day before start intake of TMC435), the levels of methadone are being determined at 11 time points. The same assessments take place at Day 7. Next to determination of levels of methadone (and TMC435) in blood of these volunteers, this study also verifies whether co-administration of both drugs trigger any clinical reactions. In addition to the standard safety assessments (analysis of urine, ECGs, blood pressure, pulse rate, hematological tests and biochemical tests of the blood), volunteers will complete 2 kinds of questionnaires, which are specifically designed to observe any physical or psychological symptoms associated with either too low (opiate withdrawal symptoms) or too high (toxicity symptoms) levels of methadone. On top of these questionnaires, the pupil diameter will be measured, as this is a measure for the level of methadone in the volunteer's blood. Both questionnaires and the pupillometry will be performed throughout the study , i. e. 7 days before TMC435 intake and as of Day-2 till and including Day 7. All assessments combined will determine whether a dose adjustment of methadone (and/or TMC435) is warranted when both drugs are used in combination. Each volunteer will take methadone (30-130 mg per day, established on an individual basis, oral syrup) for 22 consecutive days and TMC435 (150 mg per day, 2 oral capsules of 75 mg) for 7 consecutive days. Start of TMC435 intake coincides with 15th intake of methadone in the context of this study. Methadone therapy will continue after treatment with TMC435 and beyond the end of this trial, at the discretion of the responsible physician in the addiction clinic.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Receiving once daily oral methadone maintenance therapy at a stable individualized

dose of 30 to 130 mg q. d. for at least 30 days prior to screening

- Agreeing not to change the current methadone dose from screening until Day7 included

and to have a daily observed and documented methadone intake from Day-14 until Day8 and to have a daily observed and documented TMC435 intake from Day1 until Day7

- having obtained approval from his/her addiction physician for participation in the

trial and addiction physician agrees to provide medical care for the volunteer after discharge from the testing facility

Exclusion Criteria:

- No female of childbearing potential, except if using effective birth control methods

during the trial and for at least 30 days after the end of the treatment period

- No positive testing for drugs of abuse

- No positive testing for Hepatitis A, B and C and for HIV1 and 2

- impaired liver disease or other clinically relevant diseases.

This study is not yet recruiting patients. Please check back for future recruiting sites, or email, Email: info1@veritasmedicine.com

Ending date: January 2010
Last updated: September 25, 2009