TMC435-TiDP16-C108 - A Study in Healthy Volunteers Investigating the Pharmacokinetic Interaction Between TMC435 and Digoxin and Between TMC435 and Rosuvastatin
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 single-dose pharmacokinetics of digoxin or rosuvastatin , and the effect of a
      single dose of digoxin or rosuvastatin on the steady-state pharmacokinetics of TMC435. 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). Digoxin and rosuvastatin
      are expressed in the liver and intestine and mediate the transport of drugs out of the blood
      circulation. The result of this study will provide dosing recommendations for TMC435 and for
      digoxin, rosuvastatin, or other substrates using the same drug transporter molecules, 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 32 healthy volunteers to
      investigate the pharmacokinetic interaction between TMC435, at steady state, and digoxin or
      rosuvastatin at a single dose. The volunteers will be allocated to one of two panels. In
      Panel 1, volunteers will receive two treatments (Trts A and B) in a randomized order.
      Volunteers will receive digoxin 0.25 mg once daily for 1 day (Trt A) and TMC435 150 mg once
      daily for 7 days (Trt B) and 0.25 mg digoxin once daily for 1 day (Trt B). In Panel 2,
      volunteers will receive two treatments (Trts C and D) in a randomized order. Volunteers will
      receive rosuvastatin 10 mg once daily for 1 day (Trt C) and TMC435 150 mg once daily for 7
      days (Trt D) and rosuvastatin 10 mg once daily for 1 day (Trt D). 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 14 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 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 during 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 Day -1 or Day 1 (Trts A, B, C, and D), on Day
      2 (Trts A and C), before medication intake and 6 hours postdose (only vital signs and ECG) on
      Day 7 (Trts B and D), on Day 8 (Trts B and D) 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 Day 2 in Trts A and C, on Day -1 and on Day 8 of Trts B and D and during
      the 2 follow-up visits. Each volunteer is part of one panel and follows 2 treatment (Trt)
      periods, which are a minimum 14 days apart from each other. Trt period for Trts A and C - 5
      days; Trt period for Trts B and D - 11 days. Trt A and B = Panel 1, Trt C and D = Panel 2. A
      single, oral dose of digoxin (0.25 mg) or rosuvastatin (10 mg) to be given in Trt A or Trt C,
      respectively. Multiple doses of TMC435 (150 mg) for 7 days to be given in TrtB and D, with a
      single dose of digoxin or rosuvastatin on Day7, respectively.
    

Intervention name(s): Rosuvastatin; Rosuvastatin; TMC435; Digoxin; Digoxin
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): One 10-mg tablet for 1 day (Trt C).; One 10-mg tablet together with 1 capsule of TMC435 (150 mg) on Day 7 of Trt D.; One 150-mg capsule once daily for 7 days (Trts B and D).; One 0.25-mg tablet together with 1 capsule of TMC435 (150 mg) on Day 7 of Trt B.; One 0.25-mg tablet for 1 day (Trt A)
Intervention MeSH terms: Simeprevir; Digoxin; Rosuvastatin Calcium
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMC435-TiDP16-C108; TMC435-C108; TMC435; HPC; HCV; Hepatitis C