A Phase Ib, double-blind, randomized, placebo-controlled trial in genotype 1 HCV-infected patients to determine the safety, tolerability, pharmacokinetics and antiviral activity of repeated doses of TMC649128 given as monotherapy and given in combination with pegylated interferon + ribavirin

A Phase Ib, double-blind, randomized, placebo-controlled trial in genotype 1
HCV-infected patients to determine the safety, tolerability, pharmacokinetics
and antiviral activity of repeated doses of TMC649128 given as monotherapy and
given in combination with pegylated interferon + ribavirin

1. To determine the safety and tolerability of TMC649128/TMC619688 during
multiple dosing in treatmentnaïve and treatment-experienced genotype 1
HCV-infected subjects at different dose regimens as 10-days and 14-days
monotherapy.
2. To determine the pharmacokinetic profile of TMC649128, TMC619688 and
TMC649129 during multiple dosing in treatment-naïve and treatment-experienced
genotype 1 HCV-infected subjects at different dose regimens as 10-days and
14-days monotherapy.
3. To determine the dose dependency of the antiviral effect of
TMC649128/TMC619688 during multiple dosing in treatment-naïve and
treatment-experienced genotype 1 HCV-infected subjects at different dose
regimens as 10-days and 14-days monotherapy.
4. To assess the pharmacokinetic/pharmacodynamic (PK/PD) relationship for
antiviral activity, intracellular triphosphate (TMC652337) and safety of
TMC649128, TMC619688 and TMC649129.
5. To determine the short term safety and tolerability of the co-administration
of TMC649128 and PegIFN *-2a/RBV during multiple dosing for 14 days in
treatment-naïve genotype 1 HCV-infected subjects.
6. To explore the drug-drug interaction between TMC649128/TMC619688 or
TMC649129 and PegIFN *-2a/RBV during multiple dosing for 14 days in
treatment-naïve genotype 1 HCV-infected subjects.
7. To assess in a preliminary way the short term antiviral effect of the
combination of TMC649128/TMC619688 with PegIFN *-2a/RBV during a 14-day dosing
period in treatment-naïve genotype 1 HCV-infected subjects.

This study is divided in 2 parts. In the first part of the study, the study
medication will be given as monotherapy. In the second part, the study
medication will be given in combination with other medication.

The monotherapy part of this study will be performed in 30 genotype 1
HCV-infected patients, subdivided over 3 panels of 10 patients each. In each
panel patients will receive the study medication during 10 or 14 days.

The combination therapy part of this study will be performed in 20 genotype 1
HCV-infected patients in 1 panel.

Monotherapy phase
Panel 1: TMC649128 at 1000 mg q24h (n=8) or placebo (n=2) q24h on Days 1-10
under fed conditions
Panel 2: TMC649128 at 1600 mg (n=8) or placebo (n=2) q12h on Days 1-14 under
fed conditions
Panel 3: TMC649128 at a selected dose (n=8) or placebo (n=2) q12h OR q24h on
Days 1-14 under fed conditions

Combination therapy phase
Panel 4, Arm 1: placebo (q12h OR q24h, dosing regimen matched to Arm 2 of Panel
4) + PegIFN *-2a/RBV (n=10) on Days 1-14 under fed conditions
Panel 4, Arm 2: TMC649128 at a selected dose (q12h OR q24h) + PegIFN *-2a/RBV
(n=10) on Days 1-14 under fed conditions.

Procedures: pain, light bleeding, haematoma and possibly an infection