Clinical trial NCT00812331: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Keywords: Hepatitis C
TMC435
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2008-12-22
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in log10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels
timeFrame: Baseline, Day 3, and Day 7
Secondary outcomes:
measure: 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
timeFrame: Baseline, Day 3, Day 5 and Day 7
measure: 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
timeFrame: Baseline, Day 3, Day 5 and Day 7
measure: Number of Participants Who Experienced Viral Breakthrough During TMC435 Treatment Period
timeFrame: During the 7-day of TMC435 treatment period
measure: Predose Plasma Concentration (C0h) of TMC435
timeFrame: Predose on Day 7
measure: Minimum Plasma Concentration (Cmin) of TMC435
timeFrame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
measure: Maximum Plasma Concentration (Cmax) of TMC435
timeFrame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435
timeFrame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
measure: Average Steady-State Plasma Concentration (Css,av) of TMC435
timeFrame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
measure: Fluctuation Index (FI) of TMC435
timeFrame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
measure: Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24h) of TMC435
timeFrame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
measure: 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
timeFrame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
measure: Elimination Rate Constant of TMC435
timeFrame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
measure: Terminal Elimination Half-life (t1/2,Term) of TMC435
timeFrame: Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7
Other outcomes:
Locations:
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
Study officials:
affiliation: Tibotec Pharmaceuticals, Ireland
name: Tibotec Pharmaceuticals, Ireland Clinical Trial
role: STUDY_DIRECTOR
References: