Study of Changes in Hepatic Fat Following Administration of MK-4074 and Pioglitazone Hydrochloride (MK-4074-008)
Condition: Non-alcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: MK-4074 200 mg; Placebo for MK-4074; Pioglitazone hydrochloride 30 mg; Placebo for pioglitazone hydrochloride
Intervention description: 2 x 100-mg capsules, orally, twice-daily (BID) for 4 weeks; 2 x 100-mg capsules, orally, BID for 4 weeks.; 1 x 30-mg tablet, orally, once daily for 4 weeks; 1 x 30-mg tablet, orally, once daily for 4 weeks
Intervention MeSH terms: Pioglitazone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      This study will evaluate changes in liver fat content following multiple oral doses of
      MK-4074 and Pioglitazone Hydrochloride in adult males and females with fatty liver disease.
      The primary hypothesis of the study is that a multiple-dose administration of MK-4074 200 mg
      twice daily for 4 weeks results in a decrease in hepatic fat content with respect to placebo
      in adult male and female participants with hepatic steatosis (i.e., on order of 50% reduction
      in hepatic fat with respect to placebo is expected).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females must be of non-childbearing potential

          -  Body mass index (BMI) ≥32.0 kg/m^2

          -  In good health based on medical history, physical examination, vital sign
             measurements, and laboratory safety tests

          -  No clinically significant abnormality on electrocardiogram

          -  Has documented hepatic fat content ≥10% within 6 months of enrollment

          -  Maintained stable weight (by history) for at least 4 weeks

          -  Agrees not to initiate a weight loss program and agrees to maintain consistent dietary
             habits and exercise routines for the duration of the study

          -  Has a rating of 'moderate' or 'severe' steatosis on ultrasound at the prestudy
             (screening) visit

        Exclusion Criteria:

          -  Change in weight greater than 4% between prestudy visit and randomization into the
             study

          -  History of any illness that, in the opinion of the study investigator, might confound
             the results of the study or poses an additional risk to the participant

          -  Liver disease other than fatty liver or non-alcoholic steatohepatitis (NASH)

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3x the upper limit
             of normal range

          -  Serum triglyceride level >600 mg/dL

          -  History of stroke, chronic seizures, or major neurological disorder

          -  History of clinically significant endocrine, gastrointestinal, cardiovascular
             (including congestive heart failure), hematological, hepatic, immunological, renal,
             respiratory, or genitourinary abnormalities or diseases

          -  Had abdominal surgery, gastric bypass, bowel resection, recent liver biopsy, or any
             other procedure within a minimum of 4 weeks

          -  History of neoplastic disease

          -  Claustrophobia or other contraindication to magnetic resonance imaging (MRI)

          -  Have not washed off agents associated with changes in hepatic fat or used for
             treatment of Non-alcoholic fatty liver disease (NAFLD) or NASH for a minimum of 3
             months prior

          -  Consumes excessive amounts of alcohol, coffee, tea, cola, or other caffeinated
             beverages

          -  Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or
             participated in another investigational study within 4 weeks

          -  Significant multiple and/or severe allergies

          -  Intolerance or hypersensitivity to pioglitazone hydrochloride or any inactive
             ingredients

          -  Regular user of any illicit drugs or has a history of drug (including alcohol) abuse.