A Study to Assess the Anti-viral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 in Participants Infected With Hepatitis C-Virus (HCV)

July 1, 2014 updated by: Tibotec Pharmaceuticals, Ireland

An Open-label Trial in Genotype 2, 3, 4, 5 and 6 Hepatitis C-infected Subjects to Evaluate the Antiviral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 Following 7 Days Once Daily Dosing as Monotherapy.

The purpose of this study is to assess anti-viral activity (inhibition of viral growth) of TMC435350 in genotype 2,3,4,5 and 6 hepatitis C virus infected participants who have never received treatment for their hepatitis C infection.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label (all people know the identity of the intervention) study to assess the antiviral activity, safety, tolerability and pharmacokinetics (explores what the body does to the medication) of TMC435350 hereafter referred to as TMC435. Approximately 40 participants will be divided in 5 groups as per the genotype (8 participants each group). The study will include a screening phase (up to 6 weeks), treatment phase (7 days) and a follow-up phase (30-35 days after the last dose of study medication). Safety evaluations will include assessment of adverse events, clinical laboratory tests and cardiovascular safety.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brugge, Belgium
      • Brussels, Belgium
      • Bruxelles, Belgium
      • Gent, Belgium
      • Leuven, Belgium
  • Germany
      • Berlin, Germany
      • Frankfurt N/A, Germany
      • Freiburg, Germany
      • Hannover, Germany
  • Thailand
      • Bangkok, Thailand
      • Chiang Mai, Thailand

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participants with documented chronic genotype 2, 3, 4, 5 or 6 hepatitis C virus (HCV) infection
  • Participants who have never received treatment for their HCV infection
  • Participants with either no cirrhosis or up to Child Pugh A liver disease
  • Participants with plasma HCV genotype level of more than or equal to 100, 000 IU/mL at screening

Exclusion Criteria:

  • Evidence of Child Pugh B or C liver disease at screening, decompensated liver disease defined as prior or current history of ascities, hepatic encephalopathy, esophageal or gastric varices
  • Participants with diagnosed or suspected hepatocellular carcinoma
  • Participants coinfected with human immunodeficiency virus type 1 or 2, or hepatitis A or B virus infection or active tuberculosis at screening
  • Participants with any active clinically significant disease, or medical history or physical examination or electrocardiogram findings during screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Genotype 2
Participants with chronic genotype 2 hepatitis C virus (HCV) infection
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
Experimental: Genotype 3
Participants with chronic genotype 3 HCV infection
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
Experimental: Genotype 4
Participants with chronic genotype 4 HCV infection
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
Experimental: Genotype 5
Participants with chronic genotype 5 HCV infection
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
Experimental: Genotype 6
Participants with chronic genotype 6 HCV infection
Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels
Time Frame: Baseline, Day 3, and Day 7
The table below shows the mean changes from baseline in HCV RNA values (log10 IU/mL) per genotype on Day 3 and Day 7 during the TMC435 treatment period.
Baseline, Day 3, and Day 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With a Decrease From Baseline of Greater Than or Equal to 2 log10 IU/mL in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During the TMC435 Treatment Period
Time Frame: Baseline, Day 3, Day 5 and Day 7
The table below shows the number of participants with a decrease from baseline of greater than or equal to 2 log10 IU/mL in HCV RNA during the 7-day TMC435 treatment period.
Baseline, Day 3, Day 5 and Day 7
Number of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Below the Limit of Quantification (Less Than 25 IU/mL) and Limit of Detection (Less Than 25 IU/mL Undetectable) During the TMC435 Treatment Period
Time Frame: Baseline, Day 3, Day 5 and Day 7
The table below shows the number of participants with plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels below limit of quantification (less than 25 IU/mL) and limit of detection (less than 25 IU/mL undetectable), respectively, during the 7-day TMC435 treatment period.
Baseline, Day 3, Day 5 and Day 7
Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period
Time Frame: During the 7-day of TMC435 treatment period
The table below shows the number of participants who experienced viral breakthrough (defined as an increase greater than 1 log10 IU/mL in plasma level of hepatitis C virus [HCV] ribonucleic acid [RNA] from the lowest level reached, or a HCV RNA level greater than 100 IU/mL in participants who previously had HCV RNA levels undetectable [less than 25 IU/mL undetectable] or not quantifiable [less than 25 IU/mL detectable]) during the 7-day TMC435 treatment period.
During the 7-day of TMC435 treatment period
Predose Plasma Concentration (C0h) of TMC435
Time Frame: Predose on Day 7
The table below shows the median predose plasma concentration (C0h) for all participants on Day 7 of the TMC435 treatment period.
Predose on Day 7
Minimum Plasma Concentration (Cmin) of TMC435
Time Frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
The table below shows the median minimum plasma concentration (Cmin) for all participants on Day 7 of the TMC435 treatment period.
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Maximum Plasma Concentration (Cmax) of TMC435
Time Frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
The table below shows the median maximum plasma concentration (Cmax) for all participants by genotype of hepatitis C virus infection on Day 7 of the TMC435 treatment period.
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435
Time Frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
The table below shows the median time in hours for all participants (by genotype of hepatitis C virus infection) to reach the maximum plasma concentration (tmax) of TMC435 following treatment.
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Average Steady-State Plasma Concentration (Css,av) of TMC435
Time Frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
The table below shows the average steady-state TMC435 plasma concentration (Css,av) for all participants by genotype of hepatitis C virus infection on Day 7 during the TMC435 treatment period.
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Fluctuation Index (FI) of TMC435
Time Frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
The table below shows the percentage of fluctuation (FI) (defined as the variation between maximum and minimum TMC435 plasma concentrations at steady-state) of TMC435 on Day 7 for participants by genotype of hepatitis C virus infection.
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435
Time Frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
The table below shows the area under the plasma concentration-time curve from the time of administration up to 24 hours after dosing (AUC24h) of TMC435 on Day 7 for all participants by genotype of hepatitis C virus infection.
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Area Under the Plasma Concentration-time Curve From Time of Administration up to the Last Time Point With a Measurable Concentration After Dosing (AUClast) of TMC435
Time Frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
The table below shows the area under the plasma concentration-time curve from time of administration up to the last time point with a measurable concentration after dosing (AUClast) on Day 7 for TMC435 by genotype of hepatitis C virus infection.
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Elimination Rate Constant of TMC435
Time Frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
In the table below, median values for the elimination rate constant (the rate at which a drug is removed from the body expressed per unit of time, e.g., fraction/hour) for TMC435 are shown for participants by genotype of hepatitis C virus infection.
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Terminal Elimination Half-life (t1/2,Term) of TMC435
Time Frame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
The table below shows the terminal plasma half-life for TMC435 in participants analyzed by genotype of hepatitis C virus infection. The terminal plasma half-life of a drug is the time in hours required for the concentration of a drug in the body to fall to 50% after having reached a state of equilibrium following administration.
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tibotec Pharmaceuticals, Ireland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

November 1, 2009

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

December 18, 2008

First Submitted That Met QC Criteria

December 18, 2008

First Posted (Estimate)

December 22, 2008

Study Record Updates

Last Update Posted (Estimate)

July 28, 2014

Last Update Submitted That Met QC Criteria

July 1, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR012604
  • TMC435350-TiDP16-C202 (Other Identifier: Tibotec Pharmaceuticals, Ireland)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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