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

Chronic Hepatitis C Clinical Trial

Official title:

A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-7009 in Chronic Hepatitis C Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01678131
• Other study ID #: 7009-048
• Secondary ID: 2012-003284-21
• Status: Completed
• Phase: Phase 1
• Start date: October 30, 2012
• Est. completion date: September 2, 2013

Study information

• Verified date: August 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: September 2, 2013
• Est. primary completion date: August 27, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

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.

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
• 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

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.

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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