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Evaluating Fine Needle Aspiration to Measure Hepatic Vaniprevir (MK-7009) Concentrations 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 26, 2014
Last verified: September 2014
  Purpose

This study will evaluate the technical feasibility of using fine needle aspiration (FNA) of liver tissue to obtain vaniprevir (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 vaniprevir 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). The primary hypothesis is that there is a greater than 80% posterior probability that vaniprevir concentrations are successfully obtained at least 60% of the time from FNA liver samples collected at 2 of 3 specified timepoints.


Condition Intervention Phase
Chronic Hepatitis C
Drug: Vaniprevir 600 mg
Biological: Peg-IFN alfa-2b
Biological: Ribavirin
Procedure: Liver samples from FNA
Drug: Vaniprevir 300 mg
Procedure: Liver samples from 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 Vaniprevir Are Obtained by FNA [ Time Frame: Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose ] [ Designated as safety issue: No ]
    Liver samples were collected by FNA at 3 of 5 of the following specified postdose timepoints: 3, 12, 24, 48 and 72 hours after a single vaniprevir dose on Day 7. The technical success of the FNA procedure was established for a participant if vaniprevir was detected from at least 2 of the 3 FNA collection timepoints.


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: Vaniprevir 600 mg
Participants received 600 mg vaniprevir only on days 1-7, and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.
Drug: Vaniprevir 600 mg
Vaniprevir capsules, were administered orally, twice per day (BID) to achieve a final daily dose of 600 mg on Days 1 through 6; and a single dose of 600 mg, orally, on Day 7.
Other Name: MK-7009
Procedure: Liver samples from FNA
Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.
Procedure: Liver samples from CNB
Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.
Experimental: Vaniprevir 600 mg + Peg-IFN + RBV
Participants received 600 mg vaniprevir on Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.
Drug: Vaniprevir 600 mg
Vaniprevir capsules, were administered orally, twice per day (BID) to achieve a final daily dose of 600 mg on Days 1 through 6; and a single dose of 600 mg, orally, on Day 7.
Other Name: MK-7009
Biological: Peg-IFN alfa-2b
Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21
Other Name: PegIntron™
Biological: Ribavirin
Ribavirin capsules were administered on Days 1-21, orally, twice daily for a total daily dose of 600 - 1400 mg, depending on the participant's weight
Other Name: Rebetol™
Procedure: Liver samples from FNA
Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.
Procedure: Liver samples from CNB
Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.
Experimental: Vaniprevir 300 mg + Peg-IFN + RBV
Participants received 300 mg vaniprevir from Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10.
Biological: Peg-IFN alfa-2b
Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21
Other Name: PegIntron™
Biological: Ribavirin
Ribavirin capsules were administered on Days 1-21, orally, twice daily for a total daily dose of 600 - 1400 mg, depending on the participant's weight
Other Name: Rebetol™
Procedure: Liver samples from FNA
Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.
Drug: Vaniprevir 300 mg
Vaniprevir capsules were administered orally, twice per day to achieve a final daily dose of 300 mg on Days 1 through 6; and a single dose of 300 mg, orally, on Day 7.
Other Name: MK-7009
Procedure: Liver samples from CNB
Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.

  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 HCV nonstructural proteins (NS) 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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01678131

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  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
Results First Received: September 26, 2014
Last Updated: September 26, 2014
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
Interferon-alpha
Liver Extracts
Peginterferon alfa-2b
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Hematinics
Hematologic Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014