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

Primary Purpose

Chronic Hepatitis C

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Peg-Interferon

Liver Samples from FNA

Liver Samples from CNB

Blood Samples

Ribavirin

800 mg Grazoprevir

100 mg Grazoprevir

Liver samples from CNB and FNA

About this trial

This is an interventional diagnostic trial for Chronic Hepatitis C

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

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

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

Main Pt.1: 800 mg Grazoprevir

Procedural Pilot

Arm Description

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

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

800 mg Grazoprevir.

Optimization of FNA procedure.

Outcomes

Primary Outcome Measures

Number of participants from whom detectable concentrations of hepatic Grazoprevir are obtained by FNA.

Secondary Outcome Measures

Full Information

NCT ID

NCT01547312

First Posted

February 2, 2012

Last Updated

October 13, 2015

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01547312

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Withdrawn

Study Start Date

May 2012 (undefined)

Primary Completion Date

November 2012 (Anticipated)

Study Completion Date

November 2012 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

Main Pt.1: 800 mg Grazoprevir

Arm Type

Experimental

Arm Description

800 mg Grazoprevir.

Arm Title

Procedural Pilot

Arm Type

Experimental

Arm Description

Optimization of FNA procedure.

Intervention Type

Drug

Intervention Name(s)

Peg-Interferon

Other Intervention Name(s)

PegIntron

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Liver Samples from FNA

Intervention Description

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

Intervention Name(s)

Liver Samples from CNB

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Blood Samples

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ribavirin

Other Intervention Name(s)

Rebetol

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

800 mg Grazoprevir

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

100 mg Grazoprevir

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Liver samples from CNB and FNA

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of participants from whom detectable concentrations of hepatic Grazoprevir are obtained by FNA.

Time Frame

Days 7-12.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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 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.

12. IPD Sharing Statement

Learn more about this trial

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

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