TMC207-TiDP13-C117: Interaction Study in Human Immunodeficiency Virus-type 1 (HIV-1) Infected Patients With Nevirapine (NVP)
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this Phase I, open-label, single sequence drug-drug interaction trial in human
      immunodeficiency virus-type 1 infected patients is 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 and to explore the pharmacokinetics (how the drug is absorbed into the bloodstream,
      distributed in the body and eliminated from the body).
    

Detailed description: 
      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.
    

Intervention name(s): TMC207; nevirapine
Intervention type(s): Drug
Intervention MeSH terms: Nevirapine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMC207-TiDP13-C117; TMC207-C110; TMC207; drug-drug interaction; Tuberculosis; HIV; nevirapine; open-label; Pharmacokinetics