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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)

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ClinicalTrials.gov Identifier: NCT00812331
Recruitment Status : Completed
First Posted : December 22, 2008
Results First Posted : July 28, 2014
Last Update Posted : July 28, 2014
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland

Tracking Information
First Submitted Date  ICMJE December 18, 2008
First Posted Date  ICMJE December 22, 2008
Results First Submitted Date  ICMJE December 24, 2013
Results First Posted Date  ICMJE July 28, 2014
Last Update Posted Date July 28, 2014
Study Start Date  ICMJE March 2009
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 1, 2014)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2008)
Determine the antiviral effect of TMC435 during 7 days once daily dosing at 200mg orally (by mouth) as monotherapy in treatment naÃ-ve, genotype 2 to 6 HCV-infected patients.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2014)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2008)
Determine the safety, tolerability and PK profile of TMC435 during 7 days once daily dosing at 200mg as monotherapy in treatment naÃ-ve, genotype 2 to 6 HCV-infected patients.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Anti-viral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 in Participants Infected With Hepatitis C-Virus (HCV)
Official Title  ICMJE 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.
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C
Intervention  ICMJE Drug: TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
Study Arms  ICMJE
  • Experimental: Genotype 2
    Participants with chronic genotype 2 hepatitis C virus (HCV) infection
    Intervention: Drug: TMC435
  • Experimental: Genotype 3
    Participants with chronic genotype 3 HCV infection
    Intervention: Drug: TMC435
  • Experimental: Genotype 4
    Participants with chronic genotype 4 HCV infection
    Intervention: Drug: TMC435
  • Experimental: Genotype 5
    Participants with chronic genotype 5 HCV infection
    Intervention: Drug: TMC435
  • Experimental: Genotype 6
    Participants with chronic genotype 6 HCV infection
    Intervention: Drug: TMC435
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 29, 2009)
37
Original Estimated Enrollment  ICMJE
 (submitted: December 18, 2008)
40
Actual Study Completion Date  ICMJE November 2009
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Germany,   Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00812331
Other Study ID Numbers  ICMJE CR012604
TMC435350-TiDP16-C202 ( Other Identifier: Tibotec Pharmaceuticals, Ireland )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tibotec Pharmaceuticals, Ireland
Study Sponsor  ICMJE Tibotec Pharmaceuticals, Ireland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
PRS Account Tibotec Pharmaceuticals, Ireland
Verification Date July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP