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

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ClinicalTrials.gov Identifier: NCT01678131
Recruitment Status : Completed
First Posted : September 3, 2012
Results First Posted : September 29, 2014
Last Update Posted : October 18, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis C 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 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-7009 in Chronic Hepatitis C Patients
Actual Study Start Date : October 30, 2012
Actual Primary Completion Date : August 27, 2013
Actual Study Completion Date : September 2, 2013

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Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: 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.
Other Name: MK-7009

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

Procedure: Liver samples from CNB
Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.
Experimental: 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.
 Drug: 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.
Other Name: MK-7009

Biological: 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
Other Name: PegIntron™

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
Other Name: Rebetol™

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

Procedure: Liver samples from CNB
Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints.
Experimental: 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.
 Biological: 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
Other Name: PegIntron™

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
Other Name: Rebetol™

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

Drug: 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.
Other Name: MK-7009

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


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants From Whom Detectable Concentrations of Hepatic Vaniprevir Are Obtained by FNA [ Time Frame: 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01678131


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01678131    
Other Study ID Numbers: 7009-048
2012-003284-21 ( EudraCT Number )
First Posted: September 3, 2012    Key Record Dates
Results First Posted: September 29, 2014
Last Update Posted: October 18, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
 Flaviviridae Infections
Ribavirin
Peginterferon alfa-2b
Interferon alpha-2
Liver Extracts
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Hematinics
Antineoplastic Agents