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

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ClinicalTrials.gov Identifier: NCT01600976
Recruitment Status : Completed
First Posted : May 17, 2012
Last Update Posted : November 11, 2013
Sponsor:
Information provided by (Responsible Party):
Janssen Infectious Diseases BVBA

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.

Condition or disease Intervention/treatment Phase
Hepatic Impairment Drug: telaprevir Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : June 2012
Actual Primary Completion Date : October 2012
Actual Study Completion Date : November 2012

Arm Intervention/treatment
Experimental: Group 1
10 patients with moderate hepatic impairment (CPB [Child-Pugh score 7 to 9])
Drug: 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.
Other Name: VX-950

Experimental: 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%)
Drug: 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.
Other Name: VX-950

Experimental: Group 3
up to 4 patients with severe hepatic impairment (CPC [limited to Child Pugh score 10 to 12])
Drug: 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.
Other Name: VX-950




Primary Outcome Measures :
  1. Comparing the maximum plasma analyte concentration (Cmax) of telaprevir in patients of Group 2 and Group 1 [ Time Frame: 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) ]
    The pharmacokinetic parameter Cmax of telaprevir following administration of single and multiple oral doses of telaprevir in patients with moderate hepatic impairment (CPB [Child-Pugh score 7 to 9]) ie, Group 1, as compared to matched healthy patients ie, Group 2

  2. Comparing the area under the plasma concentration-time curve (AUC8h) of telaprevir in patients of Group 2 and Group 1 [ Time Frame: 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) ]
    The pharmacokinetic parameter AUC8h will be measured from time of administration up to 8 hours post dose of telaprevir following administration of single and multiple oral doses of telaprevir in patients with moderate hepatic impairment (CPB) ie, Group 1, as compared to matched healthy patients ie, Group 2

  3. Comparing the actual sampling time to reach the maximum plasma analyte concentration (tmax) of telaprevir in patients of Group 2 and Group 1 [ Time Frame: 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) ]
    The pharmacokinetic parameter tmax will be measured following administration of single and multiple oral doses of telaprevir in patients with moderate hepatic impairment (CPB) ie, Group 1, as compared to matched healthy patients ie, Group 2


Secondary Outcome Measures :
  1. Number of adverse events in Group 1 patients as a measure of safety [ Time Frame: up to Day 6 ]
    Number of adverse events in Group 1 patients as a measure of safety will be assessed following administration of single and multiple oral doses of telaprevir in patients with moderate hepatic impairment (CPB) ie, Group 1

  2. Comparing unbound fractions of telaprevir in patients of Group 1 and Group 2 [ Time Frame: up to Day 6 ]
    The unbound fractions of telaprevir after single and multiple doses of telaprevir in patients with moderate hepatic impairment ie, Group 1, as compared to matched healthy patients ie, Group 2

  3. Comparing any relationship between the measures of hepatic function and selected pharmacokinetic parameters of telaprevir in patients of Group 1 and Group 2 [ Time Frame: up to Day 6 ]
    To assess any relationship between the measures of hepatic function (ie, Child-Pugh score, albumin, bilirubin, alpha-1 acid glycoprotein, and prothrombin time) and selected pharmacokinetic parameters of telaprevir in patients with moderate hepatic impairment (CPB) ie, Group 1 and healthy patients ie, Group 2



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01600976


Locations
Czech Republic
Praha 7, Czech Republic
Germany
Kiel, Germany
Sponsors and Collaborators
Janssen Infectious Diseases BVBA
Investigators
Study Director: Janssen Infectious Diseases BVBA Clinical Trial Janssen Infectious Diseases BVBA

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Infectious Diseases BVBA
ClinicalTrials.gov Identifier: NCT01600976     History of Changes
Other Study ID Numbers: CR100872
VX-950HPC1001 ( Other Identifier: Janssen Infectious Diseases BVBA )
2012-001627-13 ( EudraCT Number )
First Posted: May 17, 2012    Key Record Dates
Last Update Posted: November 11, 2013
Last Verified: November 2013

Keywords provided by Janssen Infectious Diseases BVBA:
Hepatic impairment
Hepatitis C
Telaprevir
VX-950
Pharmacokinetics
Safety
Unbound plasma concentrations
Child-Pugh score

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases