Evaluation of Hepatic Pharmacokinetics for Grazoprevir (MK-5172) in Participants With Chronic Hepatitis C (MK-5172-022)

NCT ID: NCT01547312

Last Updated: 2015-10-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2012-11-30

Brief Summary

This study is divided into 2 segments, and proposes to qualify fine needle aspiration (FNA) as a platform to evaluate the hepatic pharmacokinetics of low and high oral doses of Grazoprevir (MK-5172) in non-cirrhotic participants chronically infected with hepatitis C virus (HCV). The first segment, is a procedural pilot conducted prior to the main study, that is aimed at ensuring optimal execution of the FNA procedure. During the procedural pilot, core needle biopsy (CNB) will be performed on participants as part of their standard of care, but no study drugs will be administered, nor will any procedures other than FNA be conducted. The second segment, the main study, is designed to evaluate the feasibility of measuring Grazoprevir by FNA. During the main study, drugs will be administered, and other additional procedures will be conducted.

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Main Pt. 2: 800 mg Grazoprevir + Peg-IFN/RBV

800 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.

Group Type: EXPERIMENTAL

Peg-Interferon

Intervention Type: DRUG

Polyethyleneglycolated Interferon alfa-2b at 1.5 ug/kg/week, administered subcutaneously, once a week, over the entire course of the study.

Liver Samples from FNA

Intervention Type: PROCEDURE

Tissue samples are collected at 3 separate visits, with each collection consisting of 3-4 fine needle aspiration (FNA) passes through the liver, guided by ultrasound.

Liver Samples from CNB

Intervention Type: PROCEDURE

Tissue samples are collected at 1 of six possible visits by core needle biopsy (CNB) of the liver.

Blood Samples

Intervention Type: PROCEDURE

Blood is collected from multiple blood draws, with the total volume for each participant not expected to exceed 500 ml.

Ribavirin

Intervention Type: DRUG

Ribavirin, 600-1400 mg administered orally, twice daily, over the entire course of the study.

800 mg Grazoprevir

Intervention Type: DRUG

800 mg Grazoprevir administered orally, once per day, for 7 consecutive days.

Main Pt. 2: 100 mg Grazoprevir + Peg-IFN/RBV

100 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.

Group Type: EXPERIMENTAL

Peg-Interferon

Intervention Type: DRUG

Polyethyleneglycolated Interferon alfa-2b at 1.5 ug/kg/week, administered subcutaneously, once a week, over the entire course of the study.

Liver Samples from FNA

Intervention Type: PROCEDURE

Tissue samples are collected at 3 separate visits, with each collection consisting of 3-4 fine needle aspiration (FNA) passes through the liver, guided by ultrasound.

Liver Samples from CNB

Intervention Type: PROCEDURE

Tissue samples are collected at 1 of six possible visits by core needle biopsy (CNB) of the liver.

Blood Samples

Intervention Type: PROCEDURE

Blood is collected from multiple blood draws, with the total volume for each participant not expected to exceed 500 ml.

Ribavirin

Intervention Type: DRUG

Ribavirin, 600-1400 mg administered orally, twice daily, over the entire course of the study.

100 mg Grazoprevir

Intervention Type: DRUG

100 mg Grazoprevir administered orally, once per day, for 7 consecutive days.

Main Pt.1: 800 mg Grazoprevir

800 mg Grazoprevir.

Group Type: EXPERIMENTAL

Liver Samples from FNA

Intervention Type: PROCEDURE

Tissue samples are collected at 3 separate visits, with each collection consisting of 3-4 fine needle aspiration (FNA) passes through the liver, guided by ultrasound.

Liver Samples from CNB

Intervention Type: PROCEDURE

Tissue samples are collected at 1 of six possible visits by core needle biopsy (CNB) of the liver.

Blood Samples

Intervention Type: PROCEDURE

Blood is collected from multiple blood draws, with the total volume for each participant not expected to exceed 500 ml.

800 mg Grazoprevir

Intervention Type: DRUG

800 mg Grazoprevir administered orally, once per day, for 7 consecutive days.

Procedural Pilot

Optimization of FNA procedure.

Group Type: EXPERIMENTAL

Liver samples from CNB and FNA

Intervention Type: PROCEDURE

Tissue samples from the liver are collected by CNB as part of standard of care, and also by FNA during a single visit.

Interventions

Peg-Interferon

Polyethyleneglycolated Interferon alfa-2b at 1.5 ug/kg/week, administered subcutaneously, once a week, over the entire course of the study.

Intervention Type: DRUG

Liver Samples from FNA

Tissue samples are collected at 3 separate visits, with each collection consisting of 3-4 fine needle aspiration (FNA) passes through the liver, guided by ultrasound.

Intervention Type: PROCEDURE

Liver Samples from CNB

Tissue samples are collected at 1 of six possible visits by core needle biopsy (CNB) of the liver.

Intervention Type: PROCEDURE

Blood Samples

Blood is collected from multiple blood draws, with the total volume for each participant not expected to exceed 500 ml.

Intervention Type: PROCEDURE

Ribavirin

Ribavirin, 600-1400 mg administered orally, twice daily, over the entire course of the study.

Intervention Type: DRUG

800 mg Grazoprevir

800 mg Grazoprevir administered orally, once per day, for 7 consecutive days.

Intervention Type: DRUG

100 mg Grazoprevir

100 mg Grazoprevir administered orally, once per day, for 7 consecutive days.

Intervention Type: DRUG

Liver samples from CNB and FNA

Tissue samples from the liver are collected by CNB as part of standard of care, and also by FNA during a single visit.

Intervention Type: PROCEDURE

Other Intervention Names

PegIntron; Rebetol

Eligibility Criteria

Inclusion Criteria

• Has chronic compensated HCV infection.
• No contraindications to CNB or FNA procedures.
• Pilot study only: All comers with chronic HCV already scheduled to undergo CNB for fibrosis staging.
• Pilot study only: Requires a diagnostic liver biopsy to monitor progression of liver disease.
• Pilot study only: Does not have cirrhosis.
• Main study only: Males or non-pregnant and postmenopausal females willing to use medically acceptable contraception during, and for 6 months or longer after study.
• Main study only: Body mass index of 18.5 - 32.0 kg/m^2.
• Main study only: Can avoid aspirin, anticoagulants, and non steroidal inflammatory agents.
• Main study only: Has undergone prior treatment or is treatment naive for chronic HCV infection.

Exclusion Criteria

• History of any of the following: stroke, chronic seizures, major neurological disorders, gastric bypass surgery or bowel resection.
• No viral response to prior interferon based therapy.
• Prior treatment for HCV with an NS3/4A protease inhibitor.
• History of either clinically significant, uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities/diseases.
• History of neoplastic or myeloproliferative disease.
• Has any of the following : cirrhosis, decompensated liver disease, or other advanced liver disease, hepatocellular carcinoma, infection with human immunodeficiency virus (HIV), or hepatitis B.
• Evidence of high grade bridging fibrosis from prior liver biopsy or chronic hepatitis not caused by HCV.
• History of illicit drug use or alcohol abuse.
• Had surgery, donated at least one unit of blood, or participated in any other investigational study within 4 weeks prior to screening visit.
• History of multiple and/or severe allergies.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

2011-004978-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5172-022

Identifier Type: -

Identifier Source: org_study_id