Evaluating Fine Needle Aspiration to Measure Hepatic Vaniprevir (MK-7009) Concentrations in Participants With Chronic Hepatitis C (MK-7009-048)
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Vaniprevir 600 mg; Peg-IFN alfa-2b; Ribavirin; Liver samples from FNA; Vaniprevir 300 mg; Liver samples from CNB
Intervention description: 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.; Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21; 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; Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.; 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.; Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.
Intervention MeSH terms: Ribavirin; Peginterferon alfa-2b; Interferon alpha-2; Liver Extracts
Phase: Phase 1
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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