TMC435-TiDP16-C114 - A Study in Healthy Volunteers Investigating the Pharmacokinetic Interaction Between TMC435 and the Antiretroviral Agents TMC278 and Tenofovir
Condition: Hepatitis C Virus
MeSH terms: Hepatitis C; Hepatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to investigate the effect of steady-state concentrations of
      TMC435 on the steady-state pharmacokinetics of TMC278 or Tenofovir , and vice versa. Steady
      state is a term which means that the drug has been given long enough so that the plasma
      concentrations will remain the same with each subsequent dose. TMC435 is being investigated
      for the treatment of chronic hepatitis C virus (HCV) infection. TMC278 and Tenofovir are two
      antiretroviral drugs for treatment of human deficiency virus (HIV) infection.
      Pharmacokinetics (pk) means how the drug is absorbed into the bloodstream, distributed in the
      body and eliminated from the body.
    

Detailed description: 
      TMC435 is being investigated for treatment of chronic HCV infection, in combination with
      Peg-IFN (pegylated interferon) and RBV (ribavirin). About 30% of all HIV infected patients
      are co-infected with HCV and need treatment for both infections. The results of this study
      will provide dosing recommendations for coadministration of TMC435 and TMC278 or Tenofovir in
      HCV-HCV co-infected patients. This is a Phase I, open-label (both participant and
      investigator know the name of the medication given at certain moment), randomized (sequence
      of treatment with study medications is assigned by chance), crossover trial in 48 healthy
      participants to investigate the pharmacokinetic interaction between TMC435 and an
      antiretroviral agent (TMC278 or tenofovir), at steady state. The participants are being
      allocated to one of two panels. In Panel 1, participants will receive three treatments
      (treatment A-B-C) in a randomized order. Participants will receive TMC435 150 mg q.d., TMC278
      25 mg q.d.and TMC278 25 mg q.d. + TMC435 150 mg q.d., respectively. All treatments will be
      administered for 11 days and with food. There will be a washout period (a period where no
      study drug will be taken in view of having all the medication eliminated from the body before
      starting a new treatment) of at least 14 days between last intake of study medication in one
      session and first intake of study medication in the subsequent session. In Panel 2,
      participants will receive three treatments (treatment D-E-F) in a randomized order.
      Participants will receive TMC435 150 mg q.d., TDF 300 mg q.d. and TDF 300 mg q.d. + TMC435
      150 mg q.d., respectively. All treatments will be administered for 7 days and with food.
      There will be a washout period of at least 7 days. Pharmacokinetic profiles of all three
      compounds will be determined through blood samples taken at regular intervals during the
      study. Safety and tolerability will be assessed during the study period and in follow-up.
      Blood and urine samples, electrocardiogram (ECG) and vital signs (blood pressure and heart
      rate) will be taken at screening, before medication intake on days 1 and 11 and on Day 12 in
      each session of Panel 1, before medication intake on days 1 and 7 and on Day 8 in each
      session of Panel 2, 5 hours post dose on Day11 and Day 7 in Panel 1 and 2, respectively and
      at the 2 follow up visits at 1 week and 4-5 weeks after last dose of study medication in the
      last session. A physical examination will be performed at screening, on day -1 (= day before
      first medication intake in each session for both panels) and during the 2 follow up visits.
      Each volunteer will receive 3 treatments for 11 or 7 days (Panel 1 and 2, respectively),
      minimum 14 or 7 days apart from each other (Panel 1 and 2, respectively). Volunteers in Panel
      1 will take oral TMC435 150 mg q.d., oral TMC278 25 mg q.d. and combined. Volunteers in Panel
      2 will take oral TMC435 150 mg q.d., oral TDF 300 mg q.d. and combined.
    

Intervention name(s): TMC435; TDF; TMC435 + TDF; TMC435 + TMC278; TMC278; TMC435
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 150 mg capsule once daily for 7 days; 300 mg tablet once daily for 7 days; 150 mg TMC435 capsule + 300 mg TDF tablet, once daily for 7 days; 150 mg TMC435 capsule + 25 mg TMC278 tablet, once daily for 11 days; 25 mg tablet once daily for 11 days; 150 mg capsule once daily for 11 days
Intervention MeSH terms: Simeprevir; Rilpivirine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMC435-TiDP16-C114; TMC435-C114; TMC435; HCV; Hepatitis C