Evaluating Fine Needle Aspiration to Measure Hepatic Vaniprevir (MK-7009) Concentrations in Participants With Chronic Hepatitis C (MK-7009-048)

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-7009 in Chronic Hepatitis C Patients

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaniprevir 600 mg<br>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<br>* 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.<br>* Other names: MK-7009;Procedure: Liver samples from FNA<br>* Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.<br>Procedure: Liver samples from CNB<br>* Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.<br>|
| Experimental: Vaniprevir 600 mg + Peg-IFN + RBV<br>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<br>* 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.<br>* Other names: MK-7009;Biological: Peg-IFN alfa-2b<br>* Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21<br>* Other names: PegIntron™;Biological: Ribavirin<br>* 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<br>* Other names: Rebetol™;Procedure: Liver samples from FNA<br>* Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.<br>Procedure: Liver samples from CNB<br>* Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.<br>|
| Experimental: Vaniprevir 300 mg + Peg-IFN + RBV<br>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<br>* Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21<br>* Other names: PegIntron™;Biological: Ribavirin<br>* 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<br>* Other names: Rebetol™;Procedure: Liver samples from FNA<br>* Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.<br>Drug: Vaniprevir 300 mg<br>* 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.<br>* Other names: MK-7009;Procedure: Liver samples from CNB<br>* Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA | 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. | Day 7 up to Day 10 at 3 of the following timepoints: 3, 12, 24, 48 and 72 hours postdose |