Evaluating Fine Needle Aspiration to Measure Hepatic Vaniprevir (MK-7009) Concentrations in Participants With Chronic Hepatitis C (MK-7009-048)
A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-7009 in Chronic Hepatitis C Patients
2 other identifiers
interventional
31
0 countries
N/A
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2012
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 30, 2012
CompletedFirst Posted
Study publicly available on registry
September 3, 2012
CompletedStudy Start
First participant enrolled
October 30, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 27, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
September 2, 2013
CompletedResults Posted
Study results publicly available
September 29, 2014
CompletedAugust 26, 2022
August 1, 2022
10 months
August 30, 2012
September 26, 2014
August 24, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
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
Study Arms (3)
Vaniprevir 600 mg
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (1)
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.
PMID: 31868916DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme LLC
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 30, 2012
First Posted
September 3, 2012
Study Start
October 30, 2012
Primary Completion
August 27, 2013
Study Completion
September 2, 2013
Last Updated
August 26, 2022
Results First Posted
September 29, 2014
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will share
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf