A Study to Evaluate Fine Needle Aspiration as a Method for MK-7009 Liver Pharmacokinetic Measurement in Participants With Chronic Hepatitis C (MK-7009-048)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01678131
First received: August 30, 2012
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

This study will evaluate the technical feasibility of using fine needle aspiration (FNA) of liver tissue to obtain MK-7009 liver pharmacokinetic (PK) data, working towards identifying a minimally invasive, reproducible platform to measure liver PK. The study will be done in 2 parts. In Part 1, participants will be randomized to one of five FNA/core needle biopsy (CNB) time-point collection sequences. In Part 2, participants will be randomized to one of two possible doses of MK-7009 and will be assigned to one of five FNA/CNB time-point collection sequences; participants in Part 2 will also receive background therapy with pegylated interferon alpha-2b (Peg-IFN alpha-2b) and ribavirin (RBV).


Condition Intervention Phase
Chronic Hepatitis C
Drug: MK-7009
Biological: Peg-IFN alfa-2b
Biological: Ribavirin
Procedure: Liver samples from FNA and CNB
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-7009 in Chronic Hepatitis C Patients

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-7009 are obtained by fine needle aspiration (FNA) [ Time Frame: Days 7 through 10, at a randomized sequence of 3 out of 5 possible collection time points (3, 12, 24, 48, or 72 hours post dose) ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: October 2012
Study Completion Date: September 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A: MK-7009 alone
Participants in this study group will receive MK-7009 alone and will have liver biopsy done by FNA and CNB.
Drug: MK-7009
MK-7009 capsules, orally, twice per day (BID) on Days 1 through 6 and a single dose, orally, on Day 7.
Procedure: Liver samples from FNA and CNB
Experimental: Treatment B: MK-7009 High Dose + Peg-IFN alpha-2b + RBV
Participants in this study group will receive MK-7009, Peg-IFN alpha-2b, and RBV and will have liver biopsy done by FNA and CNB.
Drug: MK-7009
MK-7009 capsules, orally, twice per day (BID) on Days 1 through 6 and a single dose, orally, on Day 7.
Biological: Peg-IFN alfa-2b
Administered per product label
Other Name: PegIntron™
Biological: Ribavirin
Administered per product label
Other Name: Rebetol™
Procedure: Liver samples from FNA and CNB
Experimental: Treatment C: MK-7009 MK-7009 Low Dose + Peg-IFN alpha-2b + RBV
Participants in this study group will receive MK-7009, Peg-IFN alpha-2b, and RBV and will have liver biopsy done by FNA and CNB.
Drug: MK-7009
MK-7009 capsules, orally, twice per day (BID) on Days 1 through 6 and a single dose, orally, on Day 7.
Biological: Peg-IFN alfa-2b
Administered per product label
Other Name: PegIntron™
Biological: Ribavirin
Administered per product label
Other Name: Rebetol™
Procedure: Liver samples from FNA and CNB

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body Mass Index (BMI) ≥18.5 kg/m^2 and ≤32.0 kg/m^2
  • Under evaluation for treatment of chronic hepatitis C virus (HCV)
  • Chronic compensated, genotype 1 HCV infection
  • Treatment-naïve or previously treated and tolerated at least 12 weeks of continuous licensed interferon (including pegylated interferon) and ribavirin combination therapy with at least a partial response, or previously treated with investigational products and/or vaccines, other than NS3/4A protease inhibitors, either alone or in combination with other licensed therapies
  • Able to avoid use of anticoagulants, nonsteroidal anti-inflammatory agents and aspirin for at least seven (7) days preceding the initial liver biopsy and continuing throughout the entire study
  • Female participants of childbearing potential or male participants with female sexual partners of childbearing potential must agree to use two acceptable methods of birth control from 2 weeks prior to the first dose through at least 6 months after last dose of study drug, or longer if dictated by local regulation

Exclusion criteria:

  • Pregnant, lactating, or intending to become pregnant or donate eggs, or intending to donate sperm
  • History of stroke, chronic seizures, or major neurological disorder
  • Did not achieve a viral response to prior treatment with licensed interferon-based therapy
  • Previously treated with an NS3/4A protease inhibitor (investigational or licensed)
  • Evidence or history of chronic hepatitis not caused by HCV infection including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis or autoimmune hepatitis
  • Clinical or laboratory evidence of cirrhosis or other advanced liver disease
  • Decompensated liver disease as indicated by a history of ascites, hepatic encephalopathy, or bleeding esophageal varices
  • Diagnosed with or suspected of having hepatocellular carcinoma
  • Co-infection with human immunodeficiency virus (HIV)
  • Positive hepatitis B surface antigen or other evidence of active hepatitis B infection
  • History of gastric bypass surgery or bowel resection
  • History of clinically significant uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • History of clinically significant neoplastic disease
  • Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL], wine [125 mL], or distilled spirits [25 mL]) per day
  • Regular user (including use of any illicit drugs or has a history of drug (including alcohol) abuse within the last 3 months
  • Surgery or donation of 1 unit of blood (approximately 500 mL) or participation in another investigational study within a period of 4 weeks prior to the prestudy (screening) visit
  • History of multiple and/or severe allergies, or has had an anaphylactic reaction or intolerability to prescription or nonprescription drugs or food
  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: NCT01678131     History of Changes
Other Study ID Numbers: 7009-048, 2012-003284-21
Study First Received: August 30, 2012
Last Updated: September 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Ribavirin
Peginterferon alfa-2b
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014