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.

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.