A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C-Infected Males (MK-8325-002)
Primary Purpose
Hepatitis C, Chronic
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-8325
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Panel A (GT1 10 mg)
Panel B (GT1 50 mg)
Panel C (GT1 100 mg)
Panel D (GT1 200 mg)
Panel E (GT3 10 mg)
Panel F (GT3 50 mg)
Panel G (GT3 100 mg)
Panel H (GT3 200 mg)
Panel I (GT1a 10 mg)
Panel J (GT1a 50 mg)
Placebo Panel
Arm Description
Outcomes
Primary Outcome Measures
Change from baseline to Day 5 in plasma HCV ribonucleic acid (RNA) in GT1 participants
Mean maximum reduction from baseline through Day 5 in HCV ribonucleic acid (RNA) in GT3 participants
Number of participants experiencing at least one adverse event
Number of participants discontinuing study drug due to an adverse event
Secondary Outcome Measures
Trough plasma concentration (C24hr) of MK-8325
Area under the concentration curve from Hour 0 to Hour 24 (AUC0-24hr) for MK-8325
Maximum plasma concentration (Cmax) of MK-8325
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01554189
Brief Title
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
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Terminated
Study Start Date
April 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panel A (GT1 10 mg)
Arm Type
Experimental
Arm Title
Panel B (GT1 50 mg)
Arm Type
Experimental
Arm Title
Panel C (GT1 100 mg)
Arm Type
Experimental
Arm Title
Panel D (GT1 200 mg)
Arm Type
Experimental
Arm Title
Panel E (GT3 10 mg)
Arm Type
Experimental
Arm Title
Panel F (GT3 50 mg)
Arm Type
Experimental
Arm Title
Panel G (GT3 100 mg)
Arm Type
Experimental
Arm Title
Panel H (GT3 200 mg)
Arm Type
Experimental
Arm Title
Panel I (GT1a 10 mg)
Arm Type
Experimental
Arm Title
Panel J (GT1a 50 mg)
Arm Type
Experimental
Arm Title
Placebo Panel
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
MK-8325
Intervention Description
MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to match MK-8325 capsules, orally, once per day for 5 days
Primary Outcome Measure Information:
Title
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.
Title
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.
Title
Number of participants experiencing at least one adverse event
Time Frame
Day 1 up to 56 days
Title
Number of participants discontinuing study drug due to an adverse event
Time Frame
Days 1-5
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-8325 in Hepatitis C-Infected Males (MK-8325-002)
We'll reach out to this number within 24 hrs