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