A Study to Assess Safety and Pharmacokinetics of Telaprevir in Patients With Hepatic Impairment

NCT ID: NCT01600976

Last Updated: 2013-11-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2012-11-30

Brief Summary

The purpose of this study is to determine whether the pharmacokinetic (what the body does to the drug) parameters of telaprevir are altered in patients with moderate hepatic impairment, compared to the pharmacokinetic parameters in patients with normal liver function, and measure the relative unbound plasma concentrations of telaprevir.

Detailed Description

This is a Phase I, open-label (all people know the identity of the intervention) study to investigate the single dose and steady state pharmacokinetics of telaprevir in patients with moderate hepatic impairment, and measure the relative unbound plasma concentrations of telaprevir. In addition, a small group of patients with severe hepatic impairment will be included to further characterize the pharmacokinetics of telaprevir as a function of liver disease. In this study 24 patients will be enrolled. Based upon physical examination and laboratory assessments, patients will be scored and classified into hepatic function groups on the basis of the Child-Pugh classification (Classification is based on Child-Pugh score which is used to assess prognosis of chronic hepatic disease). A Child-Pugh score of 7 to 9 is considered Child-Pugh category B (CPB) and indicative of moderate liver function impairment; a Child-Pugh score of 10 or greater is considered Child Pugh category C (CPC), indicative of severe liver impairment. Hepatic function groups will consists of Group 1: 10 patients with moderate hepatic impairment (CPB 7 to 9]); Group 2: 10 healthy control patients with normal hepatic function. Each healthy control patient is matched to a patient in Group 1 with respect to sex, age (+5 years or -5 years) and body mass index (BMI) (+15% or -15%); Group 3: 4 patients with severe hepatic impairment (CPC [limited to Child Pugh score 10 to 12]). Safety and tolerability evaluations including adverse events, clinical laboratory tests, 12-lead electrocardiogram, vital signs and physical examination will be recorded throughout the study period.

Conditions

Hepatic Impairment

Keywords

Hepatic impairment; Hepatitis C; Telaprevir; VX-950; Pharmacokinetics; Safety; Unbound plasma concentrations; Child-Pugh score

Study Design

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

Study Groups

Group 1

10 patients with moderate hepatic impairment (CPB \[Child-Pugh score 7 to 9\])

Group Type: EXPERIMENTAL

telaprevir

Intervention Type: DRUG

Type=exact number, unit=mg, number=375, form=tablet, route=oral. Multiple doses of 2 oral tablets of telaprevir will be administered every 8 hours on Days 1 to 5 and a single dose of 2 oral tablets of telaprevir will be administered in the morning on Day 6.

Group 2

10 healthy control patients with normal hepatic function. Each healthy control patient is matched to a patient in Group 1 with respect to sex, age (± 5 years) and body mass index (BMI) (± 15%)

Group Type: EXPERIMENTAL

telaprevir

Intervention Type: DRUG

Type=exact number, unit=mg, number=375, form=tablet, route=oral. Multiple doses of 2 oral tablets of telaprevir will be administered every 8 hours on Days 1 to 5 and a single dose of 2 oral tablets of telaprevir will be administered in the morning on Day 6.

Group 3

up to 4 patients with severe hepatic impairment (CPC \[limited to Child Pugh score 10 to 12\])

Group Type: EXPERIMENTAL

telaprevir

Intervention Type: DRUG

Type=exact number, unit=mg, number=375, form=tablet, route=oral. Multiple doses of 2 oral tablets of telaprevir will be administered every 8 hours on Days 1 to 5 and a single dose of 2 oral tablets of telaprevir will be administered in the morning on Day 6.

Interventions

telaprevir

Type=exact number, unit=mg, number=375, form=tablet, route=oral. Multiple doses of 2 oral tablets of telaprevir will be administered every 8 hours on Days 1 to 5 and a single dose of 2 oral tablets of telaprevir will be administered in the morning on Day 6.

Intervention Type: DRUG

Other Intervention Names

VX-950

Eligibility Criteria

Inclusion Criteria

For Group 1:

• Moderate liver function impairment (Child Pugh score of 7 to 9)
• History of hepatic disease, such as hepatitis B, previous hepatitis C, alcoholic liver disease, autoimmune hepatitis, non-alcoholic fatty liver disease, hereditary/metabolic, cryptogenic, other
• Consistent with the disease process of hepatic impairment and associated symptoms

For Group 2:

• Matched to a patient with moderate hepatic impairment with regards to sex, age (± 5 years), and BMI (± 15%) and healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality

For Group 3:

• Severe liver function impairment (limited to Child Pugh score of 10 to 12)
• Hepatic impairment due to different etiologies such as hepatitis B, previous hepatitis C, alcoholic liver disease, autoimmune hepatitis, non-alcoholic fatty liver disease, hereditary/metabolic, cryptogenic, other
• Consistent with the disease process of hepatic impairment and associated symptoms

Exclusion Criteria

For Group 1 and 3:

• Has acute infectious hepatitis
• Has grade 3 or 4 encephalopathy
• Has grade 3 or 4 creatinine elevation
• Is an active candidate for liver transplantation
• Has had variceal bleeding or spontaneous bacterial peritonitis

For Group 1 only:

• Has a porta-caval shunt or transjugular intrahepatic porto-systemic shunts

For Group 2:

Has acute hepatitis A or hepatitis B or hepatitis C infection

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

Sponsors

Janssen Infectious Diseases BVBA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Infectious Diseases BVBA Clinical Trial

Role: STUDY_DIRECTOR

Janssen Infectious Diseases BVBA

Locations

Prague, , Czechia

Kiel, , Germany

Countries

Poland; Czechia; Germany

References

Ouwerkerk-Mahadevan S, Halabi A, Cieslarova B, Aerts I, Witek J, Van Solingen-Ristea R, Luo D. Pharmacokinetics of bound and unbound telaprevir in cirrhotic patients with moderate and severe hepatic impairment. J Clin Pharmacol. 2015 Oct;55(10):1147-56. doi: 10.1002/jcph.545. Epub 2015 Jul 7.

Reference Type: DERIVED

PMID: 25975934 (View on PubMed)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=3540&filename=CR100872_CSR.pdf

A Phase I study to assess the safety and pharmacokinetics of telaprevir (VX-950) in subjects with moderate and severe hepatic impairment

Other Identifiers

VX-950HPC1001

Identifier Type: OTHER

Identifier Source: secondary_id

2012-001627-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR100872

Identifier Type: -

Identifier Source: org_study_id