Safety, Pharmacokinetics and Pharmacodynamics of Elbasvir (MK-8742) in Hepatitis C Infected Males (MK-8742-002)

• Status: Completed
• Trial end date: 2013-05-17
• Target enrollment: 0
• Participant gender: Male

Summary

The purpose of this study is to assess the safety, pharmacokinetics (PK) and pharmacodynamics of elbasvir (MK-8742) in Hepatitis C Virus (HCV)-infected participants. There will be 3 parts to this study; Part I will enroll only genotype (GT) 1 HCV-infected participants, Part II will enroll GT3 HCV-infected participants, and Part III will enroll only GT1a HCV-infected participants. All parts may run concurrently, or Parts II and III may be staggered.

Hypothesis (Part I): At a once-daily dose that is sufficiently safe and well tolerated in HCV-infected participants, elbasvir administered for 5 consecutive days has superior antiviral activity in GT1 HCV-infected participants compared to placebo, as measured by change from baseline in plasma HCV ribonucleic acid (RNA; log 10 copies/mL) at Day 5, 24-hour postdose timepoint. (a true mean viral RNA reduction of at least 3 log10 is anticipated).

Hypothesis (Part II): At a dose that is sufficiently safe in GT3 HCV-infected participants, the mean maximum reduction in HCV viral load is greater following multiple dose oral administration of elbasvir as compared to placebo.

Hypothesis (Part III): At a once-daily dose that is sufficiently safe and well tolerated in HCV-infected participants, elbasvir administered for 5 consecutive days has superior antiviral activity in GT1a HCV-infected participants compared to placebo, as measured by change from baseline in plasma HCV RNA (log 10 copies/mL) at Day 5, 24-hour postdose timepoint. (a true mean viral RNA reduction of at least 3 log10 is anticipated).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.

Criteria

Inclusion Criteria:

• Body Mass Index (BMI) of 18 to ≤ 37 kg/m^2

• Clinical diagnosis of chronic HCV infection defined by positive serology for HCV for at least 6 months and detectable HCV RNA in peripheral blood ≥105 IU/mL at screening

• Participant must be infected with HCV GT1a, GT1b, or GT 3

Exclusion Criteria:

• Co-infection with GT1 and GT3

• Estimated creatinine clearance of ≤70 mL/min based on the Cockcroft-Gault equation

• 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 at the pre-study (screening) visit

• Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior to the prestudy (screening) visit.

• Previous treatments (s) with nonstructural protein 5A (NS5A) inhibitors

• <4 weeks since administration of any experimental protease inhibitor

• Previous exposure to interferon-alpha and/or ribavirin within 3 month prior to the first dose of elbasvir in the study

• Clinical or laboratory evidence of advanced or decompensated liver disease