TMC435-TiDP16-C115 - A Study in Healthy Volunteers Investigating the Pharmacokinetic Interaction Between TMC435 and Erythromycin and Between TMC435 and Darunavir/Ritonavir (DRV/r)
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
      erythromycin or DRV/r on the steady-state pharmacokinetics of TMC435, the effect of a
      steady-state concentration of TMC435 (150 mg) on the steady-state pharmacokinetics of
      erythromycin and the effect of a steady-state concentration of TMC435 (50 mg) on the
      steady-state pharmacokinetics of DRV/r. We will also study the short-term safety and
      tolerability of TMC435 given alone and given togehter with erythromycin (Panel 1) or DRV/r
      (Panel 2). Steady state is a term that 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. 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). Erythromycin is an
      antibiotic and Darunavir/ritonavir (DRV/r) is currently indicated for the treatment of HIV
      infection. TMC435 is metabolized by the degradation enzyme CYP3A. Erythromycin and DRV/r are
      respectively moderate and strong inhibitors of the degradation enzyme CYP3A. The result of
      this study will provide dosing recommendations for TMC435 and for erythromycin or DRV/r, when
      being coadministered. 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, at steady state, and DRV/r or
      erythromycin, at steady-state. The volunteers will be allocated to one of two panels. In
      Panel 1, volunteers will receive three treatments (Trts A, B and C) in a randomized order.
      Volunteers will receive TMC435 150 mg once daily for 7 days (Trt A) and erythromycin 500 mg
      three times daily for 6 days + a morning dose on day 7 (Trt B) and TMC435 150 mg once daily
      for 7 days + erythromycin 500 mg three tmes daily for 7 days (Trt C). In Panel 2, volunteers
      will receive three treatments (Trts D, E and F) in a randomized order. Volunteers will
      receive TMC435 150 mg once daily for 7 days (Trt D), DRV/r 800/100 mg once daily for 7 days
      (Trt E) and TMC435 50 mg once daily for 7 days + DRV/r 800/100 mg once daly for 7 days (Trt
      F). In both panels, there will be a washout period (a period when no study drug will be
      taken, in order to have all the medication eliminated from the body before starting a new
      treatment) of at least 10 (Panel 1) or 7 (Panel 2) days between last intake of the study
      medication in one session and the first intake of study medication in the subsequent session.
      Pharmacokinetic profiles of all four compounds (TMC435, DRV, ritonavir and erythromycin) will
      be determined through blood samples taken at regular intervals during the study. Safety and
      tolerability will be assessed during the study period and during follow up. Blood and urine
      samples, electrocardiogram (ECG) and vital signs (blood pressure and heart rate) will be
      taken at screening, on Day 1, Day 7 and Day 8 and at the follow up visit at 1 week 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)
      or Day 1, on Day 8 and during the follow-up visit. Volnteers will be admitted to the unit on
      Day-1, discharged on Day2, re-admitted on Day6 and discharged again on Day8. Each volunteer
      follows 3 treatment (Trt) periods, which are a minimum 10 days (Panel 1) or 7 days (Panel 2)
      apart from each other. All treatment periods take 7 days and all drugs are for oral intake.
      Panel 1: Trt A = 150 mg TMC435 once daily; Trt B = 500 mg erythromycin three times daily; Trt
      C: combining Trt A + B. Panel 2: Trt D = Trt A; Trt E = 800/100 mg DRV/r once daily; Trt D =
      50 mg TMC435 once daily + Trt E.
    

Intervention name(s): erythromycin; Ritonavir; TMC435; Darunavir; TMC435; erythromycin
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 500 mg tablets three times a day for 6 days + 1 morning dose for 7th day (Trt B); 100 mg tablet once daily for 7 days (Trt E, F); 150 mg capsule once daily for 7 days (Trt A, C, D); 2 x 400 mg tablet once daily for 7 days (Trt E, F); 50 mg capsule once daily for 7 days (Trt F); 500 mg tablets three times a day for 7 days (Trt C)
Intervention MeSH terms: Ritonavir; Darunavir; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate; Simeprevir
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMC435-TiDP16-C115; TMC435-C115; TMC435; HCV; Hepatitis C; Hep C; healthy volunteers