TMC278-TiDP6-C121: Drug-drug Interaction Trial to Investigate the Potential Interaction Between TMC278 25 mg Daily and Methadone, at Steady State.
The purpose of this Phase I, open-label, single-sequence drug-drug interaction trial in patients on stable methadone maintenance therapy is to investigate the potential interaction between TMC278 25 mg daily and methadone, at steady-state.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Open-label, Single-sequence Drug-drug Interaction Trial in Subjects on Stable Methadone Maintenance Therapy, to Investigate the Potential Interaction Between TMC278 25 mg q.d. and Methadone, at Steady-state.|
- To evaluate the effect of steady-state TMC278 25 mg q.d. on the steady-state pharmacokinetics of R- and S-methadone after 11 days of TMC278 intake.
- To evaluate after 11 days of TMC278 intake: the potential effect of TMC278 on the pharmacodynamic effects of methadone therapy; the steady-state pharmacokinetics of TMC278 25 mg daily; the short-term safety and tolerability of coadministration.
|Study Start Date:||October 2008|
|Study Completion Date:||June 2009|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
This is a Phase I, open-label, single-sequence drug-drug interaction trial in patients on stable methadone maintenance therapy, to investigate the potential interaction between TMC278 25 mg daily and methadone, at steady-state. TMC278 is under development for the treatment of HIV-1 infected patients. The trial population will consist of 16 HIV-negative patients on stable methadone maintenance therapy. Patients will receive TMC278 25 mg daily for 11 days, added to their current methadone therapy. The current methadone dosage for each patient is not to be changed from screening until Day 11 inclusive. Methadone dose will be individualized for each patient and should be between 60 and 150 mg daily. Full 24 hour pharmacokinetic profiles of R- and S-methadone will be determined on Day -1 (methadone alone) and on Day 11 (methadone + TMC278). A full 24 hour pharmacokinetic profile of TMC278 will be determined on Day 11 (methadone + TMC278). Pharmacodynamic assessments of the symptoms of methadone withdrawal (Short Opiate Withdrawal Scale (SOWS), Desires for Drugs Questionnaire (DDQ), pupillometry) will be performed on Day -7 and daily from Day -3 until Day 11, within 2 hours before the intake of methadone. Safety and tolerability will be evaluated continuously throughout the trial. Patients will receive TMC278 added to their current methadone therapy in the following way: methadone individualized maintenance therapy, 60 to 150 mg daily from Day -14 to 11 and TMC278 25 mg tablet by mouth daily from Day 1 to 11. TMC278 and methadone will both be taken within 10 minutes after completion of a breakfast.