• Pharmacokinetic parameters of R- and S-methadone will be assessed. [ Time Frame: Levels of R- and S-methadone are assessed on samples collected during 12 consecutive days/visits. During 2 days, an intensive sampling is scheduled (11 samples taken in 12 hours on Day-1 + Day7). During 10 remaining days, 1 sample has to be collected. ] [ Designated as safety issue: No ]
  

• Short-term safety and tolerability will be assessed [ Time Frame: Day-14 (14 days prior first intake TMC435), Day-1 (2 time points), 1, 3, 7 (2 time points) and 8 ] [ Designated as safety issue: No ]
  
• Pharmacodynamic responses based on questionnaires and pupilometry will be assessed [ Time Frame: On Day-7 (=7 days before first TMC435 intake) and on Day-2 till and including Day7 ] [ Designated as safety issue: No ]
  
• Pharmacokinetic parameters of TMC435 will be assessed [ Time Frame: Day4 till and including Day7 ] [ Designated as safety issue: No ]
  

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.