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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01547312
First received: February 2, 2012
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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 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 MK-5172 by FNA. During the main study, drugs will be administered, and other additional procedures will be conducted.


Condition Intervention Phase
Chronic Hepatitis C
Drug: Peg-Interferon
Procedure: Liver Samples from FNA
Procedure: Liver Samples from CNB
Procedure: Blood Samples
Drug: Ribavirin
Drug: 800 mg MK-5172
Drug: 100 mg MK-5172
Procedure: Liver samples from CNB and FNA
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-5172 in Participants With Chronic Hepatitis C

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of participants from whom detectable concentrations of hepatic MK-5172 are obtained by FNA. [ Time Frame: Days 7-12. ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: May 2012
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Main Pt. 2: 800 mg MK-5172 + Peg-IFN/RBV
800 mg MK-5172 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 Name: 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 Name: Rebetol
Drug: 800 mg MK-5172
800 mg MK-5172 administered orally, once per day, for 7 consecutive days.
Experimental: Main Pt. 2: 100 mg MK-5172 + Peg-IFN/RBV
100 mg MK-5172 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 Name: 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 Name: Rebetol
Drug: 100 mg MK-5172
100 mg MK-5172 administered orally, once per day, for 7 consecutive days.
Experimental: Main Pt.1: 800 mg MK-5172
800 mg MK-5172.
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 MK-5172
800 mg MK-5172 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01547312     History of Changes
Other Study ID Numbers: 5172-022, 2011-004978-29
Study First Received: February 2, 2012
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferons
Liver Extracts
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Hematinics
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014