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

Hepatitis C Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00812331
• Other study ID #: CR012604
• Secondary ID: TMC435350-TiDP16
• Status: Completed
• Phase: Phase 2
• First received: December 18, 2008
• Last updated: July 1, 2014
• Start date: March 2009
• Est. completion date: November 2009

Study information

• Verified date: July 2014
• Source: Tibotec Pharmaceuticals, Ireland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsGermany: Bundesinstitut für Arzneimittel und MedizinprodukteThailand: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• TMC435
From Day 1 to Day 7 all participants will take 200 mg TMC435350 as a single medication orally (by mouth) once daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tibotec Pharmaceuticals, Ireland

Countries where clinical trial is conducted

Belgium,  Germany,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Day 3, and Day 7	No
Secondary	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.	Baseline, Day 3, Day 5 and Day 7	No
Secondary	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.	Baseline, Day 3, Day 5 and Day 7	No
Secondary	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.	During the 7-day of TMC435 treatment period	No
Secondary	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.	Predose on Day 7	No
Secondary	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.	Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7	No
Secondary	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.	Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7	No
Secondary	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.	Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7	No
Secondary	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.	Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7	No
Secondary	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.	Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7	No
Secondary	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.	Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7	No
Secondary	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.	Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7	No
Secondary	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.	Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7	No
Secondary	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.	Predose, and at 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose on Day 7	No