TMC435-TiDP16-C113: A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics of TMC435

NCT ID: NCT01046058

Last Updated: 2013-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2011-07-31

Brief Summary

The purpose of the study is to investigate the effect of moderate and severe hepatic impairment on the pharmacokinetics of TMC435. Pharmacokinetics means how the drug is absorbed into the bloodstream, distributed in the body and eliminated from the body. In addition, the short-term safety and tolerability of TMC435 in participants with hepatic impairment will be determined. The results of this study will guide dose recommendations for TMC435 in patients with impaired liver function.

Detailed Description

This is a Phase I, open-label trial to investigate the pharmacokinetics (how the drug is absorbed into the bloodstream, distributed in the body and eliminated from the body) of TMC435 in 8 participants with moderate hepatic impairment and 8 participants with severe hepatic impairment as compared to 8 participants with normal hepatic function, matched for age, gender, race, BMI (body mass index = weight in kilogram divided by square of height in meters) and smoking status. Open-label means that the study doctor and the participants know what treatment will be assigned to them. All participants will receive 150 mg of TMC435 by mouth for 7 days. Participants with severe hepatic impairment will be treated when the pharmacokinetic profiles of TMC435 in participants with moderate hepatic impairment have been evaluated. The dose of TMC435 may be changed for participants with severe hepatic impairment after evaluation of the blood levels TMC435 in participants with moderately impaired hepatic function. Tolerability and safety of TMC435 will be assessed throughout the trial period. Illnesses and side effects will be checked at every visit. Blood samples will be taken at screening, on the day before TMC435 intake, on days 2, 3, 5, 6, 7 (11 times), 8 and 9 and at 2 follow-up visits. Blood levels of TMC435 will be determined on days 2, 5, 6, 7, 8 and 9. Urine samples, ECG and vital signs will be taken at screening, twice on day 7 and at 2 follow-up visits. A physical examination will be done at screening, on the day before TMC435 intake, on day 9 and at both follow-up visits. All participants will receive a 150 mg dose of TMC435 for 7 days, given by mouth as 2 capsules of 75 mg. After evaluation of the pharmacokinetic profiles of TMC435 in participants with moderate hepatic impairment, the dose may be changed for participants with severe hepatic impairment.

Conditions

Hepatitis C Virus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Panel A: TMC435 150 mg

Participants enrolled in Panel A had moderate hepatic failure and received TMC435 150 mg once daily for 7 days.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

150 mg (two 75-mg capsules) orally (by mouth) once daily for 7 days

Panel B: TMC435 150 mg

Participants enrolled in Panel B had severe hepatic impairment and received TMC435 150 mg once daily for 7 days after the safety of TMC435 150 mg once daily for 7 days was evaluated in participants enrolled in Panel A.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

150 mg (two 75-mg capsules) orally (by mouth) once daily for 7 days

Interventions

TMC435

150 mg (two 75-mg capsules) orally (by mouth) once daily for 7 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants with hepatic impairment: Moderate or severe hepatic impairment, clinically diagnosed as Child Pugh B or C
• Stable liver cirrhosis and hepatic impairment for at least 3 months prior to the start of the study. Participants with normal hepatic function: Healthy based on a medical evaluation including medical history, physical examination, blood tests and electrocardiogram

Exclusion Criteria

• Participants with hepatic impairment: Fluctuating or rapidly deteriorating hepatic function as indicated by widely varying or worsening of clinical and/or laboratory signs of hepatic impairment within 3 months prior or within the screening period
• Cirrhosis due to chronic hepatitis B or C infection. Participants with normal hepatic function: History or presence of hepatic disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Tibotec Pharmaceuticals, Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tibotec Pharmaceuticals Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceutical Limited

Locations

Anaheim, California, United States

Orlando, Florida, United States

San Antonio, Texas, United States

Countries

United States

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=1034&filename=CR016783_CSR.pdf

A Phase I, open-label, sequential trial to investigate the pharmacokinetics, safety, and tolerability of TMC435 in subjects with moderately or severely impaired hepatic function

Other Identifiers

TMC435-TiDP16-C113

Identifier Type: OTHER

Identifier Source: secondary_id

CR016783

Identifier Type: -

Identifier Source: org_study_id