Study to Examine Multiple Doses of TMC647055 in Combination With Telaprevir
Study to Examine Multiple Doses of TMC647055 in Combination With Telaprevir
The purpose of this study is to assess safety, tolerability, pharmacokinetics (how the drug
 is absorbed into the bloodstream) and antiviral activity of repeated doses of TMC647055 given
 in combination with telaprevir in HCV infected patients. TMC647055 is being investigated for
 the treatment of hepatitis C infection. Telaprevir has recently been approved in the USA and
 in Europe for the treatment of chronic hepatitis C infected patients.
This is a phase I, open label trial in genotype 1 hepatitis C virus (HCV) infected patients.
 The study population consists of 16 adult patients. TMC647055 is given as an oral solution
 and telaprevir (TVR) is given as oral tablets. Patients found to be eligible after the
 screening visit will be divided over 2 panels that will be performed sequentially. In the
 first panel, 8 patients will receive TMC647055 at a dose of 500 mg twice a day in combination
 with TVR at a dose of 1125 mg twice a day for 10 consecutive days. In the second panel, 8
 subjects will receive TMC647055 in combination with TVR for 14 days. TMC647055 and TVR dose
 will be decided based on results from panel 1. TMC647055 dose will not be higher than 1000 mg
 twice a day and TVR dose will be 1125 mg twice a day or 1500 mg twice a day. It could also be
 decided to change duration of panel 2 to 10 days. In that case, the timing of assessments of
 panel 1 will be followed. For the duration of dosing in the 2 panels, patients will remain on
 site. Immediately after the last dose in panels 1 and 2, patients will start the extension
 phase. In this phase, patients will receive TVR at a dose of 750 mg every 8 hours for 12
 weeks in combination with pegylated interferon alfa (Peg IFN)(180ug subcutaneous once weekly)
 and ribavirin (RBV) (1000 or 1200 mg per day orally depending on weight in 2 divided doses).
 After that they will receive either 12 or 36 weeks of PegIFN -RBV treatment at the same dose
 regimen, depending on virus levels at week 4 and 12 in this extension phase. In the extension
 phase, patients will come to the site for visits at week 2, 4, 8, 12, 16, 24, 36 (if
 applicable) and 48 (if applicable). Patients who prematurely drop out in panel 1 or 2, will
 have a follow-up visit at 2 and 4 weeks after their last dose. Patients participating in the
 extension phase will have a follow-up visit at 4 and 12 weeks after their last dose. Safety
 and tolerability will be evaluated throughout the study.
Inclusion Criteria:

 -  genotype 1a or 1b HCV infection with HCV RNA level > 100,000 IU/mL

 -  A documented prior relapser patient to previous treatment regimens or treatment-naïve

 -  Patient must have documentation of a liver biopsy within 3 years before the screening
 visit or must agree to have a fibroscan/elastography examination within the screening
 period

 -  Patient is judged to be medically stable on the basis of physical examination, medical
 history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening

 Exclusion Criteria:

 -  Evidence of liver cirrhosis

 -  Evidence of decompensated liver disease

 -  Evidence of any other cause of significant liver disease in addition to hepatitis C

 -  receiving or having received any treatment for HCV during the 6 months before
 screening

 -  History or evidence of current abuse of alcohol, barbiturate, amphetamine,
 recreational or narcotic drug use, which in the investigator's opinion would
 compromise subject's safety and/or compliance with the study procedures