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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Non-alcoholic Fatty Liver Disease

Treatments: Drug: Pioglitazone hydrochloride 30 mg; Drug: Placebo for MK-4074; Drug: Placebo for pioglitazone hydrochloride; Drug: MK-4074 200 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01431521

4074-008

Details and patient eligibility

About

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).

Enrollment: 31 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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31 participants in 4 patient groups, including a placebo group

MK-4074

Experimental group

Description:

Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.

Treatment:

Drug: MK-4074 200 mg

Placebo for MK-4074

Placebo Comparator group

Description:

Participants will receive oral doses of placebo to match MK-4074 twice daily for 4 weeks.

Treatment:

Drug: Placebo for MK-4074

Pioglitazone

Experimental group

Description:

Participants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks.

Treatment:

Drug: Pioglitazone hydrochloride 30 mg

Placebo for pioglitazone

Placebo Comparator group

Description:

Participants will receive oral doses of placebo to match pioglitazone hydrochloride once daily for 4 weeks.

Treatment:

Drug: Placebo for pioglitazone hydrochloride