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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: telaprevir

Study type: Interventional

Funder types: Industry

Identifiers

NCT01600976

VX-950HPC1001 (Other Identifier)

2012-001627-13 (EudraCT Number)

CR100872

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Group 1

Experimental group

Description:

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

Treatment:

Drug: telaprevir

Group 2

Experimental group

Description:

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%)

Treatment:

Drug: telaprevir

Group 3

Experimental group

Description:

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

Treatment:

Drug: telaprevir