TMC435-TiDP16-C123 - A Study in Healthy Volunteers Investigating the Pharmacokinetic Interaction Between TMC435 and the Antiretroviral Agents Efavirenz and Raltegravir
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 efavirenz or raltegravir , 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. Efavirenz and
      raltegravir 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 hepatitis C virus (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
      efavirenz or raltegravir in HIV-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 volunteers to investigate the pharmacokinetic interaction between TMC435
      and an antiretroviral agent (efavirenz or raltegravir), at steady state. The volunteers are
      being allocated to one of two panels. In Panel 1, volunteers will receive three treatments
      (treatment A-B-C) in a randomized order. Volunteers will receive TMC435 150 mg q.d.,
      efavirenz 600 mg q.d. and efavirenz 600 mg q.d. + TMC435 150 mg q.d., respectively. All
      treatments will be administered for 14 days. 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,
      volunteers will receive three treatments (treatment D-E-F) in a randomized order. Volunteers
      will receive TMC435 150 mg q.d., raltegravir 400 mg b.i.d. and raltegravir 400 mg b.i.d. +
      TMC435 150 mg q.d., respectively. All treatments will be administered for 7 days. 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 14 and on Day 15 in each session
      of Panel 1, before medication intake on Days 1 and 7 and on Day8 in each session of Panel 2,
      6 hours post dose on Day14 and Day7 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 on Day15 in Panel 1, on Day-1 and on Day8 of
      Panel 2 and during the 2 follow up visits. Each volunteer will receive 3 treatments for 14 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 efavirenz 600
      mg q.d. and combined. Volunteers in Panel 2 will take oral TMC435 150 mg q.d., oral
      raltegravir 400 mg b.i.d. and combined.
    

Intervention name(s): raltegravir; TMC435 + raltegravir; TMC435; TMC435 + efavirenz; TMC435; efavirenz
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): One 400 mg tablet twice daily for 7 days; Two 75 mg TMC435 capsules once daily and one 400 mg raltegravir tablet for 7 days; Two 75 mg capsules once daily for 7 days; Two 75 mg TMC435 capsules + one 600 mg TMC278 tablet, once daily for 14 days; Two 75 mg capsules once daily for 14 days; One 600 mg tablet once daily for 14 days
Intervention MeSH terms: Efavirenz; Raltegravir Potassium; Simeprevir
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMC435-TiDP16-C123; TMC435-C123; TMC435; HCV; Hepatitis C