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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Chronic Hepatitis C

Treatments: Drug: Vaniprevir 600 mg; Procedure: Liver samples from CNB; Biological: Peg-IFN alfa-2b; Drug: Vaniprevir 300 mg; Procedure: Liver samples from FNA; Biological: Ribavirin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01678131

7009-048

2012-003284-21 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 3 patient groups

Vaniprevir 600 mg

Experimental group

Description:

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.

Treatment:

Procedure: Liver samples from CNB

Procedure: Liver samples from FNA

Drug: Vaniprevir 600 mg

Vaniprevir 600 mg + Peg-IFN + RBV

Experimental group

Description:

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.

Treatment:

Biological: Ribavirin

Biological: Peg-IFN alfa-2b

Procedure: Liver samples from CNB

Procedure: Liver samples from FNA

Drug: Vaniprevir 600 mg

Vaniprevir 300 mg + Peg-IFN + RBV

Experimental group

Description:

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.

Treatment:

Biological: Ribavirin

Drug: Vaniprevir 300 mg

Biological: Peg-IFN alfa-2b

Procedure: Liver samples from CNB

Procedure: Liver samples from FNA