TMC649128HPC1002 - a Trial inGenotype 1 Hepatitis C Virus (HCV) - Infected Participants to Determine the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of TMC649128, Alone and Combined With Pegylated Interferon + Ribavirin

• Status: Terminated
• Trial end date: 2011-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine in genotype 1 Hepatitis C Virus (HCV)-infected participants, the safety, tolerability, pharmacokinetics (how the drug is absorbed in the body, how it is distributed within the body and removed from the body over time) and antiviral activity of repeated doses of TMC649128 given as monotherapy and given in combination with pegylated interferon + ribavirin. We assess the pharmacokinetic/pharmacodynamic (how the study medication affects the body) (PK/PD) relationship for antiviral activity, active metabolite and safety of TMC649128 and its metabolites. We determine the short term safety and tolerability of the co-administration of TMC649128 and pegylated interferon + ribavirin during multiple dosing for 14 days in treatment-naive genotype 1 HCV-infected participants. We explore the effect of pegylated interferon + ribavirin on the pharmacokinetics of TMC649128 during the multiple dosing for 14 days in treatment-naive genotype 1 HCV-infected participants. We also assess in a preliminary way the short term antiviral effect of the combination of TMC649128 with pegylated interferon + ribavirin during a 14-day dosing period in treatment-naive genotype 1 HCV-infected participants.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tibotec BVBA
• Treatments: Antiviral Agents; Interferons; Ribavirin

Criteria

Inclusion Criteria:

• Documented chronic (> 6 months) genotype 1a or 1b Hepatitis C virus (HCV) infection

• Treatment-naive volunteer, meaning never received (Peg)IFN, RBV or any other approved or investigational treatment for chronic HCV infection (Panels 1, 2, 3 or 4) OR volunteer is a documented prior non-responder or relapser subject to previous treatment regimens (IFN/RBV or pegylated IFN/RBV) but has stopped this treatment at least 6 months before screening

• volunteer has never received a HCV polymerase inhibitor and HCV protease inhibitor treatment was stopped since at least one year (Panels 1, 2 or 3)

• Volunteer with HCV plasma RNA levels of > 100,000 IU/mL at screening

• Body Mass Index of 18.0 to 35.0 kg/m2

• Healthy based on a medical evaluation including medical history, physical examination, blood tests, vital signs, and electrocardiogram.

Exclusion Criteria:

• Evidence of liver cirrhosis

• Historical liver biopsy graded as liver cirrhosis or evidence for the presence of oesophageal varices or a transient elastography (Fibroscan) result of more than 14.6 kPa within 2 years prior to screening

• Evidence of decompensated liver disease defined as prior history or current evidence of ascites, hepatic encephalopathy, bleeding oesophageal or gastric varices

• Evidence of renal dysfunction, documented by an estimated creatinine clearance below 70 mL/min

• Evidence of any other cause of significant liver disease in addition to hepatitis C, this may include but is not limited to hepatitis B, drug- or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis, or primary biliary cirrhosis

• Volunteer with diagnosed or suspected hepatocellular carcinoma

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

• Volunteer coinfected with Human Immunodeficiency Virus-1 (HIV-1) or HIV-2, or hepatitis A or B virus infection, or clinically active tuberculosis at study screening.