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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00812331
First received: December 18, 2008
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Drug: TMC435
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels [ Time Frame: Baseline, Day 3, and Day 7 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period [ Time Frame: During the 7-day of TMC435 treatment period ] [ Designated as safety issue: No ]
    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.

  • Predose Plasma Concentration (C0h) of TMC435 [ Time Frame: Predose on Day 7 ] [ Designated as safety issue: No ]
    The table below shows the median predose plasma concentration (C0h) for all participants on Day 7 of the TMC435 treatment period.

  • 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 ] [ Designated as safety issue: No ]
    The table below shows the median minimum plasma concentration (Cmin) for all participants on Day 7 of the TMC435 treatment period.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 37
Study Start Date: March 2009
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00812331

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
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
  More Information

No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00812331     History of Changes
Other Study ID Numbers: CR012604, TMC435350-TiDP16-C202
Study First Received: December 18, 2008
Results First Received: December 24, 2013
Last Updated: July 1, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Thailand: Food and Drug Administration

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Hepatitis C
TMC435

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Viral, Human
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 27, 2014