Safety, Pharmacokinetics and Pharmacodynamics of Elbasvir (MK-8742) in Hepatitis C Infected Males (MK-8742-002)
Condition: Hepatitis, Viral, Human
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis, Viral, Human; Hepatitis
Intervention: Elbasvir; Placebo
Intervention description: Elbasvir was administered orally by tablet(s); Dose-matched placebo tablets were administered orally.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 48.0
Sex: Male
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

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).
    

Eligibility 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