A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C-Infected Males (MK-8325-002)

A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C Infected Males

This study is being done to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of MK-8325 in male hepatitis C virus (HCV)-infected participants. There will be 3 parts to this study. Part I will enroll only genotype 1 (GT1) HCV patients, Part II will enroll only genotype 3 (GT3) HCV-infected participants, and Part III will enroll only GT1a HCV-infected participants. All parts may run concurrently, or may be staggered as needed by the clinical sites.

Study Overview

• Status: Terminated
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: MK-8325; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria:

• Body mass index (BMI) of 18 to ≤37 kg/m^2
• Diagnosis of chronic HCV infection
• Must be infected with HCV GT1a, GT1b, or GT3

Exclusion criteria:

• Co-infection with GT1 and GT3 HCV
• History of stroke, chronic seizures, or major neurological disorder
• History of clinically significant endocrine, gastrointestinal (excepting HCV infection), cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• History of neoplastic disease
• Positive Hepatitis B surface antigen
• History of human immunodeficiency virus (HIV) infection or positive HIV serology
• Major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior
• History of significant multiple and/or severe allergies (including latex allergy), or anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Current regular user (including "recreational use") of any illicit drugs or history of drug (including alcohol) abuse within approximately 2 months
• Evidence or history of chronic hepatitis not caused by HCV including but not limited to non-HCV viral hepatitis, non-alcoholic steatohepatitis (NASH), drug-induced hepatitis, autoimmune hepatitis
• Previous treatments(s) with nonstructural 5A (NS5A) protein inhibitors
• Treatment with protease inhibitor(s) <30 days prior to study enrollment
• Previous exposure to interferon-alpha and/or ribavirin within 3 months prior to the first dose of MK-8325 in the study
• Clinical or laboratory evidence of advanced or decompensated liver disease; evidence of bridging fibrosis or higher grade fibrosis (Metavir score ≥3) from prior liver biopsy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Panel A (GT1 10 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
EXPERIMENTAL: Panel B (GT1 50 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
EXPERIMENTAL: Panel C (GT1 100 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
EXPERIMENTAL: Panel D (GT1 200 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
EXPERIMENTAL: Panel E (GT3 10 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
EXPERIMENTAL: Panel F (GT3 50 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
EXPERIMENTAL: Panel G (GT3 100 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
EXPERIMENTAL: Panel H (GT3 200 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
EXPERIMENTAL: Panel I (GT1a 10 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
EXPERIMENTAL: Panel J (GT1a 50 mg)	Drug: MK-8325; MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
PLACEBO_COMPARATOR: Placebo Panel	Drug: Placebo; Placebo to match MK-8325 capsules, orally, once per day for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline to Day 5 in plasma HCV ribonucleic acid (RNA) in GT1 participants	Day 1 predose and 2, 4, 8, 12, 24 and 36 hours post-dose, Days 3 and 4 predose, Day 5 predose and 2, 4, 8, 12, and 24 hours post-dose.
Mean maximum reduction from baseline through Day 5 in HCV ribonucleic acid (RNA) in GT3 participants	Day 1 predose and 2, 4, 8, 12, 24 and 36 hours post-dose, Days 3 and 4 predose, Day 5 predose and 2, 4, 8, 12, and 24 hours post-dose.
Number of participants experiencing at least one adverse event	Day 1 up to 56 days
Number of participants discontinuing study drug due to an adverse event	Days 1-5

Secondary Outcome Measures

Outcome Measure	Time Frame
Trough plasma concentration (C24hr) of MK-8325	Day 1 predose and 0.25 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16 and 24 hours post-dose and Day 5 predose and 0.25, 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16, 24, 36,48, 72, 96, 120, 144, 168, 192, 216, and 240 hours post-dose
Area under the concentration curve from Hour 0 to Hour 24 (AUC0-24hr) for MK-8325	Day 1 predose and 0.25 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16 and 24 hours post-dose and Day 5 predose and 0.25, 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16 and 24 hours post-dose
Maximum plasma concentration (Cmax) of MK-8325	Day 1 predose and 0.25 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16 and 24 hours post-dose and Day 5 predose and 0.25, 0.5, 1, 2, 4, 5, 6, 7, 8, 12, 16, 24, 36,48, 72, 96, 120, 144, 168, 192, 216, and 240 hours post-dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: March 12, 2012
• First Submitted That Met QC Criteria: March 12, 2012
• First Posted (ESTIMATE): March 14, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): July 21, 2015
• Last Update Submitted That Met QC Criteria: July 20, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: 8325-002; 2011-006263-22 (EUDRACT_NUMBER)