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

Phase 1

Withdrawn

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

• Registration Number: NCT01547312
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2012-02-02
• Study First Submitted QC: 2012-03-02
• Study First Posted: 2012-03-07
• Study Start: 2012-05
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Status Verified: 2015-10
• Last Update Submitted: 2015-10-13
• Last Update Posted: 2015-10-14

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Main Pt. 2: 800 mg Grazoprevir + Peg-IFN/RBV	Liver Samples from CNB	800 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt. 2: 800 mg Grazoprevir + Peg-IFN/RBV	Liver Samples from FNA	800 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt. 2: 800 mg Grazoprevir + Peg-IFN/RBV	Peg-Interferon	800 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt. 2: 800 mg Grazoprevir + Peg-IFN/RBV	Blood Samples	800 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt. 2: 100 mg Grazoprevir + Peg-IFN/RBV	Peg-Interferon	100 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt. 2: 100 mg Grazoprevir + Peg-IFN/RBV	Liver Samples from FNA	100 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt. 2: 100 mg Grazoprevir + Peg-IFN/RBV	Liver Samples from CNB	100 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt.1: 800 mg Grazoprevir	Liver Samples from FNA	800 mg Grazoprevir.
Main Pt.1: 800 mg Grazoprevir	Blood Samples	800 mg Grazoprevir.
Procedural Pilot	Liver samples from CNB and FNA	Optimization of FNA procedure.
Main Pt. 2: 100 mg Grazoprevir + Peg-IFN/RBV	100 mg Grazoprevir	100 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt. 2: 800 mg Grazoprevir + Peg-IFN/RBV	Ribavirin	800 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt. 2: 800 mg Grazoprevir + Peg-IFN/RBV	800 mg Grazoprevir	800 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt. 2: 100 mg Grazoprevir + Peg-IFN/RBV	Blood Samples	100 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.
Main Pt.1: 800 mg Grazoprevir	Liver Samples from CNB	800 mg Grazoprevir.
Main Pt.1: 800 mg Grazoprevir	800 mg Grazoprevir	800 mg Grazoprevir.
Main Pt. 2: 100 mg Grazoprevir + Peg-IFN/RBV	Ribavirin	100 mg Grazoprevir combined with Peg-Interferon/Ribavirin treatment.

Primary Outcome Measures

Name	Time	Method
Number of participants from whom detectable concentrations of hepatic Grazoprevir are obtained by FNA.	Days 7-12.