Phase 1
N=31
Study of Changes in Hepatic Fat Following Administration of MK-4074 and Pioglitazone Hydrochloride (MK-4074-008)
Non-alcoholic Fatty Liver Disease
Bottom Line
View on ClinicalTrials.gov: NCT01431521 ↗Enrolled (actual)
31
Serious AEs
0.0%
Results posted
Mar 2016
Primary outcome: Primary: Percent Change From Baseline in Hepatic Fat — -35.73; -18.04; 8.63 Percent change — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MK-4074 200 mg (Drug); Placebo for MK-4074 (Drug); Pioglitazone hydrochloride 30 mg (Drug); Placebo for pioglitazone hydrochloride (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Sep 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Hepatic Fat |
-35.73; -18.04; 8.63 | <0.001 sig |
| PRIMARY Number of Participants Experiencing One or More Adverse Events (AE) |
4; 4; 5 | — |
| PRIMARY Number of Participants Who Discontinued Study Drug Due to an AE |
0; 0; 0 | — |
| SECONDARY Percent Change From Baseline in Alanine Transaminase (ALT) |
-9.82; -20.21; -3.47 | >0.200 |
| SECONDARY Percent Change From Baseline Aspartate Transaminase (AST) |
-6.74; -13.95; -3.28 | >0.200 |
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.
Data sourced from ClinicalTrials.gov (NCT01431521). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.