Clinical trial NCT01600976: A Study to Assess Safety and Pharmacokinetics of Telaprevir in Patients With Hepatic Impairment
Official title: A Phase I Study to Assess the Safety and Pharmacokinetics of Telaprevir (VX-950) in Subjects With Moderate and Severe Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic impairment
Hepatitis C
Telaprevir
VX-950
Pharmacokinetics
Safety
Unbound plasma concentrations
Child-Pugh score
Lead sponsor: Janssen Infectious Diseases BVBA
Sponsor class: INDUSTRY
First posted: 2012-05-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Comparing the maximum plasma analyte concentration (Cmax) of telaprevir in patients of Group 2 and Group 1
timeFrame: Day 1 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), Day 2 to Day 5 (predose), Day 6 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), and Day 7 (24 hour)
measure: Comparing the area under the plasma concentration-time curve (AUC8h) of telaprevir in patients of Group 2 and Group 1
timeFrame: Day 1 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), Day 2 to Day 5 (predose), Day 6 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), and Day 7 (24 hour)
measure: Comparing the actual sampling time to reach the maximum plasma analyte concentration (tmax) of telaprevir in patients of Group 2 and Group 1
timeFrame: Day 1 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), Day 2 to Day 5 (predose), Day 6 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), and Day 7 (24 hour)
Secondary outcomes:
measure: Number of adverse events in Group 1 patients as a measure of safety
timeFrame: up to Day 6
measure: Comparing unbound fractions of telaprevir in patients of Group 1 and Group 2
timeFrame: up to Day 6
measure: Comparing any relationship between the measures of hepatic function and selected pharmacokinetic parameters of telaprevir in patients of Group 1 and Group 2
timeFrame: up to Day 6
Other outcomes:
Locations:
city: Praha 7
country: Czech Republic
city: Kiel
country: Germany
Study officials:
affiliation: Janssen Infectious Diseases BVBA
name: Janssen Infectious Diseases BVBA Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.