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

NCT01391117 | Terminated Phase 1

• 2 other identifiers: CR017992TMC649128HPC1002
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 3

Brief 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.

Conditions

Hepatitis C Virus

Keywords

TMC649128; HCV; TMC649128HPC1002; Hepatitis C; Hep C

Outcome Measures

Primary Outcomes (4)

• Change in the steady-state plasma concentrations of TMC649128.

  From baseline up to Day 80 per panel (panel 1 + panel 2 + panel 3).

• Change in the steady-state plasma concentrations of TMC649128 following co-administration with pegylated interferon + ribavirin.

  From baseline up to day 84 (panel 4).

• Viral load decreases and/or changes of viral load from baseline (HCV RNA copies/ml) (PK/PD).

  For monotherapy from baseline up to Day 80 per panel (panel 1 + panel 2 + panel 3) and for combination therapy from baseline up to day 84 (panel 4).

• Number of participants with adverse events as a measure of safety and tolerability - TMC649128 as monotherapy and when co-administered with pegylated interferon + ribavirin.

  For monotherapy from baseline up to Day 80 per panel (panel 1 + panel 2 + panel 3) and for combination therapy from baseline up to day 84 (panel 4).

Secondary Outcomes (2)

• Antiviral activity (HCV RNA levels) of TMC649128 as monotherapy and when co-administered with pegylated interferon + ribavirin.

  For monotherapy from baseline up to Day 80 per panel (panel 1 + panel 2 + panel 3) and for combination therapy from baseline up to day 84 (panel 4)

• Antiviral activity (viral breakthrough) of TMC649128 as monotherapy and when co-administered with pegylated interferon + ribavirin.

  For monotherapy from baseline up to Day 80 per panel (panel 1 + panel 2 + panel 3) and for combination therapy from baseline up to day 84 (panel 4).

Study Arms (10)

010

EXPERIMENTAL

TMC649128 panel 4 arm 2: 10 participants receive PegIFN a-2a/RBV in combination with TMC649128 administered q12h or q24h for 14 days. Actual dose and dose regimen (12h or 24h) is to be selected based on panels 1 2 and 3.

Drug: TMC649128

001

EXPERIMENTAL

TMC649128. panel 1: 8 participants receive a q24h regimen at 1000 mg of TMC649128.

Drug: TMC649128.

002

PLACEBO COMPARATOR

placebo. panel 1: 2 participants receive placebo at a q24h regimen.

Drug: placebo.

003

EXPERIMENTAL

TMC649128. panel 2 arm 1: 8 participants receive a q12h regimen of TMC649128 at a selected dose based on results of panel 1.

Drug: TMC649128.

004

PLACEBO COMPARATOR

placebo. panel 2 arm 1: 2 participants receive placebo at a q12h regimen.

Drug: placebo.

005

EXPERIMENTAL

TMC649128. panel 2 arm 2: 8 participants receive a q24h regimen TMC649128 at a dose based on results of panel 1.

Drug: TMC649128.

006

PLACEBO COMPARATOR

placebo. panel 2 arm 2: 2 participants receive placebo at a q24h regimen.

Drug: placebo.

007

EXPERIMENTAL

TMC649128 panel 3: 8 participants receive TMC649128. Actual dose and dose regimen (q12h or q24h) to be selected based on the results of the panels 1 and 2.

Drug: TMC649128

008

PLACEBO COMPARATOR

placebo. panel 3: 2 participants receive placebo. Actual dose and dose regimen (q12h or q24h) to be selected based on the results of the panels 1 and 2.

Drug: placebo.

009

PLACEBO COMPARATOR

placebo panel 4 arm 1: 10 participants receive PegIFN a-2a/RBV in combination with placebo administered q12h or q24h for 14 days. Actual dose and dose regimen (12h or 24h) is to be selected based on panels 1 2 and 3.

Drug: placebo

Interventions

placebo. DRUG

panel 1: 2 participants receive placebo at a q24h regimen.

002

TMC649128. DRUG

panel 2, arm 1: 8 participants receive a q12h regimen of TMC649128 at a selected dose based on results of panel 1.

003

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tibotec BVBA: lead

Study Sites (3)

Unknown Facility

Zuidlaren, Netherlands

Location

Unknown Facility

Krakow, Poland

Location

Unknown Facility

Warsaw, Poland

Location

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Tibotec-Virco Virology BVBA Clinical Trial

  Tibotec BVBA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2011
• First Posted: July 11, 2011
• Study Start: June 1, 2011
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: October 26, 2012

Record last verified: 2012-10

Locations

PL (2); NL (1)