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

• 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: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

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

• 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

Arms and Interventions

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

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

• 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

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Study Data/Documents: CSR Synopsis 

• 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
• 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:

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