TMC125-TiDP2-C188: A Phase I, Open-label Trial to Investigate the Pharmacokinetic Effect of Multiple-dose TMC125 on Buprenorphine and Norbuprenorphine Administered in HIV-negative Patients on Stable Buprenorphine/Naloxone Maintenance Therapy.

This is a Phase I, open-label (patient and trial doctor know what medication you are taking at any point in time during the trial), add-on trial in patients who are on stable sublingual (placed in the mouth under the tongue until it disolves) buprenorphine/naloxone maintenance therapy, to investigate the potential pharmacokinetic effect of multiple-dose TMC125 on buprenorphine and norbuprenorphine administered as buprenorphine/naloxone. The study population will consist of 16 HIV-negative opioid-dependent patients on stable individualized sublingual buprenorphine/naloxone maintenance therapy. Patients will first participate in a 2 weeks run-in period with supervised buprenorphine/naloxone intake. Subsequently, patients will receive TMC125 200 mg orally twice daily for 14 days added to their buprenorphine/naloxone treatment. During the treatment period from Day 1 to Day 14, the individualized buprenorphine/naloxone treatment will be continued with co-administration of TMC125. Full pharmacokinetic profiles of buprenorphine and norbuprenorphine will be determined on Days -1 and 14 up to 24 hours postdose. Full pharmacokinetic profiles of TMC125 will be determined on Day 14 up to 12 hours postdose. Pharmacodynamic assessments of symptoms of opiate withdrawal and excess will be performed. The short-term safety and tolerability will be assessed throughout the trial. Patients will firstparticipate in a 2 weeks run-in period with supervised buprenorphine/naloxone intake. Subsequently, patients will receive 2 tablets of 100 mg TMC125 twice daily for 14 days added to their buprenorphine/naloxone treatment. During the treatment period from Day 1 to Day 14, the individualized buprenorphine/naloxone treatment will be continued with co-administration of TMC125.

Inclusion criteria

• Body Mass Index (BMI) of 18.0 to 30.0 kg/m2, extremes included. BMI is calculated as the weight (in kg) divided by the square of height (in m)
• Receiving once daily buprenorphine/naloxone maintenance therapy at a stable individualized dose formulated and administered as sublingual tablets with a maximum daily dose of 16/4 mg of buprenorphine/naloxone. Patients using buprenorphine only are also eligible if they switch to buprenorphine/naloxone minimally 2 weeks before randomization
• The patient agrees not to change the current buprenorphine/naloxone therapy from Screening until Day 14 included (switching buprenorphine to buprenorphine/naloxone between Screening and Day -14 is allowed)and to have a daily observed and documented buprenorphine/naloxone intake from Day -14 until Day 15
• General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial.

Exclusion criteria

• A positive HIV-1 or HIV-2 test at Screening
• Female, except if postmenopausal since more than 2 years, or posthysterectomy, or post-tubal ligation (without reversal operation)
• Evidence of current use of barbiturate, amphetamine, recreational or narcotic drug use (cocaine, inhalants, stimulants), sedative hypnotics (benzodiazepines), excessive alcohol or opioids. The drug screening involves analysis for amphetamines, barbiturates, benzodiazepines, cocaine and opioids
• Hepatitis A infection (confirmed by hepatitis A antibody IgM), or hepatitis B infection (confirmed by hepatitis B surface antigen) at study screening
• Currently active gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease