Study of Changes in Hepatic Fat Following Administration of MK-4074 and Pioglitazone Hydrochloride (MK-4074-008)

• Status: Completed
• Trial end date: 2012-10-01
• Target enrollment: 0
• Participant gender: All

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).

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

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Pioglitazone

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.