Clinical trial NCT01431521: Study of Changes in Hepatic Fat Following Administration of MK-4074 and Pioglitazone Hydrochloride (MK-4074-008)
Official title: An Exploratory Study to Evaluate Changes in Hepatic Fat Following Multiple-Dose Administration of MK-4074 and Pioglitazone Hydrochloride
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-alcoholic Fatty Liver Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-09-09
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Percent Change From Baseline in Hepatic Fat
timeFrame: Baseline and Week 4
measure: Number of Participants Experiencing One or More Adverse Events (AE)
timeFrame: Up to 10 weeks
measure: Number of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Percent Change From Baseline in Alanine Transaminase (ALT)
timeFrame: Baseline and Week 4
measure: Percent Change From Baseline Aspartate Transaminase (AST)
timeFrame: Baseline and Week 4
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: