Back to resultsA Study to Assess the Anti-viral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 in Participants Infected With Hepatitis C-Virus (HCV)
Primary Purpose
Hepatitis C
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TMC435
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C focused on measuring Hepatitis C, TMC435
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Genotype 2
Genotype 3
Genotype 4
Genotype 5
Genotype 6
Arm Description
Participants with chronic genotype 2 hepatitis C virus (HCV) infection
Participants with chronic genotype 3 HCV infection
Participants with chronic genotype 4 HCV infection
Participants with chronic genotype 5 HCV infection
Participants with chronic genotype 6 HCV infection
Outcomes
Primary Outcome Measures
Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
Full Information
NCT ID
NCT00812331
First Posted
December 18, 2008
Last Updated
July 1, 2014
Sponsor
Tibotec Pharmaceuticals, Ireland
1. Study Identification
Unique Protocol Identification Number
NCT00812331
Brief Title
A Study to Assess the Anti-viral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 in Participants Infected With Hepatitis C-Virus (HCV)
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.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tibotec Pharmaceuticals, Ireland
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
Keywords
Hepatitis C, TMC435
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Genotype 2
Arm Type
Experimental
Arm Description
Participants with chronic genotype 2 hepatitis C virus (HCV) infection
Arm Title
Genotype 3
Arm Type
Experimental
Arm Description
Participants with chronic genotype 3 HCV infection
Arm Title
Genotype 4
Arm Type
Experimental
Arm Description
Participants with chronic genotype 4 HCV infection
Arm Title
Genotype 5
Arm Type
Experimental
Arm Description
Participants with chronic genotype 5 HCV infection
Arm Title
Genotype 6
Arm Type
Experimental
Arm Description
Participants with chronic genotype 6 HCV infection
Intervention Type
Drug
Intervention Name(s)
TMC435
Intervention Description
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.
Primary Outcome Measure Information:
Title
Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels
Description
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.
Time Frame
Baseline, Day 3, and Day 7
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Baseline, Day 3, Day 5 and Day 7
Title
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
Description
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.
Time Frame
Baseline, Day 3, Day 5 and Day 7
Title
Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period
Description
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.
Time Frame
During the 7-day of TMC435 treatment period
Title
Predose Plasma Concentration (C0h) of TMC435
Description
The table below shows the median predose plasma concentration (C0h) for all participants on Day 7 of the TMC435 treatment period.
Time Frame
Predose on Day 7
Title
Minimum Plasma Concentration (Cmin) of TMC435
Description
The table below shows the median minimum plasma concentration (Cmin) for all participants on Day 7 of the TMC435 treatment period.
Time Frame
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Title
Maximum Plasma Concentration (Cmax) of TMC435
Description
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 Frame
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Title
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435
Description
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.
Time Frame
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Title
Average Steady-State Plasma Concentration (Css,av) of TMC435
Description
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.
Time Frame
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Title
Fluctuation Index (FI) of TMC435
Description
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.
Time Frame
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Title
Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435
Description
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.
Time Frame
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Title
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
Description
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.
Time Frame
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Title
Elimination Rate Constant of TMC435
Description
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.
Time Frame
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Title
Terminal Elimination Half-life (t1/2,Term) of TMC435
Description
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.
Time Frame
Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tibotec Pharmaceuticals, Ireland Clinical Trial
Organizational Affiliation
Tibotec Pharmaceuticals, Ireland
Official's Role
Study Director
Facility Information:
City
Brugge
Country
Belgium
City
Brussels
Country
Belgium
City
Bruxelles
Country
Belgium
City
Gent
Country
Belgium
City
Leuven
Country
Belgium
City
Berlin
Country
Germany
City
Frankfurt N/A
Country
Germany
City
Freiburg
Country
Germany
City
Hannover
Country
Germany
City
Bangkok
Country
Thailand
City
Chiang Mai
Country
Thailand
12. IPD Sharing Statement
Learn more about this trial
A Study to Assess the Anti-viral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 in Participants Infected With Hepatitis C-Virus (HCV)
We'll reach out to this number within 24 hrs