Clinical trial NCT01554189: A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C-Infected Males (MK-8325-002)
Official title: A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C Infected Males
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatitis C, Chronic
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-03-14
Enrollment: 37
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline to Day 5 in plasma HCV ribonucleic acid (RNA) in GT1 participants
timeFrame: 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.
measure: Mean maximum reduction from baseline through Day 5 in HCV ribonucleic acid (RNA) in GT3 participants
timeFrame: 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.
measure: Number of participants experiencing at least one adverse event
timeFrame: Day 1 up to 56 days
measure: Number of participants discontinuing study drug due to an adverse event
timeFrame: Days 1-5
Secondary outcomes:
measure: Trough plasma concentration (C24hr) of MK-8325
timeFrame: 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
measure: Area under the concentration curve from Hour 0 to Hour 24 (AUC0-24hr) for MK-8325
timeFrame: 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
measure: Maximum plasma concentration (Cmax) of MK-8325
timeFrame: 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
Other outcomes:
Locations:
Study officials:
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