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

Hepatitis C, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01554189
• Other study ID #: 8325-002
• Secondary ID: 2011-006263-22
• Status: Terminated
• Phase: Phase 1
• First received: March 12, 2012
• Last updated: July 20, 2015
• Start date: April 2012
• Est. completion date: April 2013

Study information

• Verified date: July 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 37
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• MK-8325
MK-8325 capsules, orally, once per day for 5 days, at a dose determined by panel assignment (10-200 mg)
• Placebo
Placebo to match MK-8325 capsules, orally, once per day for 5 days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Primary	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.	No
Primary	Number of participants experiencing at least one adverse event		Day 1 up to 56 days	Yes
Primary	Number of participants discontinuing study drug due to an adverse event		Days 1-5	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No