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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01431521
First received: September 7, 2011
Last updated: October 16, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Non-alcoholic Fatty Liver Disease
Drug: MK-4074 200 mg
Drug: Placebo for MK-4074 100 mg
Drug: Pioglitazone hydrochloride 30 mg
Drug: Placebo for pioglitazone hydrochloride 30 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: An Exploratory Study to Evaluate Changes in Hepatic Fat Following Multiple-Dose Administration of MK-4074 and Pioglitazone Hydrochloride

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percent Change from Baseline in Hepatic Fat for MK-4074 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent Change from Baseline in Hepatic Fat for Pioglitazone Hydrochloride [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
  • Percent Change from Baseline in Alanine Transaminase(ALT) [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
  • Percent Change from Baseline Aspartate Transaminase (AST) [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: October 2011
Study Completion Date: October 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-4074 Drug: MK-4074 200 mg
2 x 100-mg capsules, orally, twice-daily (BID) for 4 weeks
Placebo Comparator: Placebo for MK-4074 Drug: Placebo for MK-4074 100 mg
2 x 100-mg capsules, orally, BID for 4 weeks.
Experimental: Pioglitazone Drug: Pioglitazone hydrochloride 30 mg
1 x 30-mg tablet, orally, once daily for 4 weeks
Placebo Comparator: Placebo for pioglitazone Drug: Placebo for pioglitazone hydrochloride 30 mg
1 x 30-mg tablet, orally, once daily for 4 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01431521     History of Changes
Other Study ID Numbers: 4074-008
Study First Received: September 7, 2011
Last Updated: October 16, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014