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

NCT ID: NCT01678131

Last Updated: 2022-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-30
• Study Completion Date: 2013-09-02

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.

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Vaniprevir 600 mg

Intervention Type: DRUG

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.

Liver samples from FNA

Intervention Type: PROCEDURE

Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.

Liver samples from CNB

Intervention Type: PROCEDURE

Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.

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.

Group Type: EXPERIMENTAL

Vaniprevir 600 mg

Intervention Type: DRUG

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

Intervention Type: BIOLOGICAL

Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21

Ribavirin

Intervention Type: BIOLOGICAL

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 from FNA

Intervention Type: PROCEDURE

Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.

Liver samples from CNB

Intervention Type: PROCEDURE

Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.

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.

Group Type: EXPERIMENTAL

Peg-IFN alfa-2b

Intervention Type: BIOLOGICAL

Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21

Ribavirin

Intervention Type: BIOLOGICAL

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 from FNA

Intervention Type: PROCEDURE

Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.

Vaniprevir 300 mg

Intervention Type: DRUG

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 from CNB

Intervention Type: PROCEDURE

Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: 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

Intervention Type: BIOLOGICAL

Liver samples from FNA

Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints.

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

Liver samples from CNB

Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.

Intervention Type: PROCEDURE

Other Intervention Names

MK-7009; PegIntron™; Rebetol™; MK-7009

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Gao W, Webber AL, Maxwell J, Anderson M, Caro L, Chung C, Miltenburg AMM, Popa S, Van Dyck K, Wenning L, Mangin E, Fandozzi C, Railkar R, Shire NJ, Fraser I, Howell B, Talal AH, Stoch SA. Fine-Needle Aspiration for the Evaluation of Hepatic Pharmacokinetics of Vaniprevir: A Randomized Trial in Patients With Hepatitis C Virus Infection. Clin Pharmacol Ther. 2020 Jun;107(6):1325-1333. doi: 10.1002/cpt.1737. Epub 2020 Feb 8.

Reference Type: DERIVED

PMID: 31868916 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

2012-003284-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

7009-048

Identifier Type: -

Identifier Source: org_study_id