TMC435-TiDP16-C108 - A Study in Healthy Volunteers Investigating the Pharmacokinetic Interaction Between TMC435 and Digoxin and Between TMC435 and Rosuvastatin

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.