A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C-Infected Males (MK-8325-002 AM1)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01554189
First received: March 12, 2012
Last updated: August 8, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: MK-8325
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C Infected Males

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change from baseline to Day 5 in plasma HCV ribonucleic acid (RNA) in GT1 participants [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • Mean maximum reduction from baseline through Day 5 in HCV ribonucleic acid (RNA) in GT3 participants [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • Number of participants experiencing at least one adverse event [ Time Frame: Day 1 up to 56 days ] [ Designated as safety issue: Yes ]
  • Number of participants discontinuing study drug due to an adverse event [ Time Frame: Days 1-5 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Trough plasma concentration (C24hr) of MK-8325 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Area under the concentration curve from Hour 0 to Hour 24 (AUC0-24hr) for MK-8325 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration (Cmax) of MK-8325 [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: April 2012
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01554189

Locations
Belgium
MSD Belgium BVBA/SPRL
Brussels, Belgium
Germany
Merck Sharp & Dohme GmbH
Haar, Germany
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01554189     History of Changes
Other Study ID Numbers: 8325-002, 2011-006263-22
Study First Received: March 12, 2012
Last Updated: August 8, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic

ClinicalTrials.gov processed this record on July 26, 2014