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

A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-5172 in Participants With Chronic Hepatitis C

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.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: Peg-Interferon; Procedure: Liver Samples from FNA; Procedure: Liver Samples from CNB; Procedure: Blood Samples; Drug: Ribavirin; Drug: 800 mg Grazoprevir; Drug: 100 mg Grazoprevir; Procedure: Liver samples from CNB and FNA

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 for Main study only:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Main Pt. 2: 800 mg Grazoprevir + Peg-IFN/RBV; 800 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.	Drug: Peg-Interferon; Polyethyleneglycolated Interferon alfa-2b at 1.5 ug/kg/week, administered subcutaneously, once a week, over the entire course of the study.; Other Names: PegIntron; Procedure: 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.; Procedure: Liver Samples from CNB; Tissue samples are collected at 1 of six possible visits by core needle biopsy (CNB) of the liver.; Procedure: Blood Samples; Blood is collected from multiple blood draws, with the total volume for each participant not expected to exceed 500 ml.; Drug: Ribavirin; Ribavirin, 600-1400 mg administered orally, twice daily, over the entire course of the study.; Other Names: Rebetol; Drug: 800 mg Grazoprevir; 800 mg Grazoprevir administered orally, once per day, for 7 consecutive days.
Experimental: Main Pt. 2: 100 mg Grazoprevir + Peg-IFN/RBV; 100 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.	Drug: Peg-Interferon; Polyethyleneglycolated Interferon alfa-2b at 1.5 ug/kg/week, administered subcutaneously, once a week, over the entire course of the study.; Other Names: PegIntron; Procedure: 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.; Procedure: Liver Samples from CNB; Tissue samples are collected at 1 of six possible visits by core needle biopsy (CNB) of the liver.; Procedure: Blood Samples; Blood is collected from multiple blood draws, with the total volume for each participant not expected to exceed 500 ml.; Drug: Ribavirin; Ribavirin, 600-1400 mg administered orally, twice daily, over the entire course of the study.; Other Names: Rebetol; Drug: 100 mg Grazoprevir; 100 mg Grazoprevir administered orally, once per day, for 7 consecutive days.
Experimental: Main Pt.1: 800 mg Grazoprevir; 800 mg Grazoprevir.	Procedure: 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.; Procedure: Liver Samples from CNB; Tissue samples are collected at 1 of six possible visits by core needle biopsy (CNB) of the liver.; Procedure: Blood Samples; Blood is collected from multiple blood draws, with the total volume for each participant not expected to exceed 500 ml.; Drug: 800 mg Grazoprevir; 800 mg Grazoprevir administered orally, once per day, for 7 consecutive days.
Experimental: Procedural Pilot; Optimization of FNA procedure.	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants from whom detectable concentrations of hepatic Grazoprevir are obtained by FNA.	Days 7-12.

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Anticipated): November 1, 2012
• Study Completion (Anticipated): November 1, 2012

Study Registration Dates

• First Submitted: February 2, 2012
• First Submitted That Met QC Criteria: March 2, 2012
• First Posted (Estimate): March 7, 2012

Study Record Updates

• Last Update Posted (Estimate): October 14, 2015
• Last Update Submitted That Met QC Criteria: October 13, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Hematinics; Interferons; Ribavirin; Liver Extracts; Grazoprevir
• Other Study ID Numbers: 5172-022; 2011-004978-29 (EudraCT Number)