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

Phase 1

Completed

• Conditions: Chronic Hepatitis C
• Interventions: Drug: Vaniprevir 600 mg; Procedure: Liver samples from FNA; Biological: Peg-IFN alfa-2b; Procedure: Liver samples from CNB; Biological: Ribavirin; Drug: Vaniprevir 300 mg

• Registration Number: NCT01678131
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-08-30
• Study First Submitted QC: 2012-08-30
• Study First Posted: 2012-09-03
• Study Start: 2012-10-30
• Primary Completion: 2013-08-27
• Study Completion: 2013-09-02
• Results First Submitted: 2014-09-26
• Results First Submitted QC: 2014-09-26
• Results First Posted: 2014-09-29
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-24
• Last Update Posted: 2022-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vaniprevir 300 mg + Peg-IFN + RBV	Vaniprevir 300 mg	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.
Vaniprevir 600 mg	Liver samples from CNB	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.
Vaniprevir 600 mg + Peg-IFN + RBV	Vaniprevir 600 mg	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.
Vaniprevir 600 mg	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.
Vaniprevir 600 mg	Liver samples from FNA	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.
Vaniprevir 600 mg + Peg-IFN + RBV	Ribavirin	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.
Vaniprevir 600 mg + Peg-IFN + RBV	Peg-IFN alfa-2b	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.
Vaniprevir 600 mg + Peg-IFN + RBV	Liver samples from FNA	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.
Vaniprevir 600 mg + Peg-IFN + RBV	Liver samples from CNB	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.
Vaniprevir 300 mg + Peg-IFN + RBV	Peg-IFN alfa-2b	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.
Vaniprevir 300 mg + Peg-IFN + RBV	Ribavirin	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.
Vaniprevir 300 mg + Peg-IFN + RBV	Liver samples from FNA	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.
Vaniprevir 300 mg + Peg-IFN + RBV	Liver samples from CNB	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.

Primary Outcome Measures

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