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

NCT01431521 | Completed Phase 1 Results

• 1 other identifier: 4074-008
• Study Type: interventional
• Target: 31
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Non-alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (3)

• Percent Change From Baseline in Hepatic Fat

  Hepatic fat content was assessed via magnetic resonance imaging (MRI) prior to first dose administration and following 4 weeks of treatment. Percent change in hepatic fat fraction from baseline was calculated for each of the 9 liver regions separately and then these were averaged to calculate overall percent change from baseline for each participant.

  Baseline and Week 4

• Number of Participants Experiencing One or More Adverse Events (AE)

  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

  Up to 10 weeks

• Number of Participants Who Discontinued Study Drug Due to an AE

  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

  Up to 4 weeks

Secondary Outcomes (2)

• Percent Change From Baseline in Alanine Transaminase (ALT)

  Baseline and Week 4

• Percent Change From Baseline Aspartate Transaminase (AST)

  Baseline and Week 4

Study Arms (4)

MK-4074

EXPERIMENTAL

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

Drug: MK-4074 200 mg

Placebo for MK-4074

PLACEBO COMPARATOR

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

Drug: Placebo for MK-4074

Pioglitazone

EXPERIMENTAL

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

Drug: Pioglitazone hydrochloride 30 mg

Placebo for pioglitazone

PLACEBO COMPARATOR

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

Drug: Placebo for pioglitazone hydrochloride

Interventions

MK-4074 200 mg DRUG

2 x 100-mg capsules, orally, twice-daily (BID) for 4 weeks

MK-4074

Placebo for MK-4074 DRUG

2 x 100-mg capsules, orally, BID for 4 weeks.

Placebo for MK-4074

Pioglitazone hydrochloride 30 mg DRUG

1 x 30-mg tablet, orally, once daily for 4 weeks

Pioglitazone

Placebo for pioglitazone hydrochloride DRUG

1 x 30-mg tablet, orally, once daily for 4 weeks

Placebo for pioglitazone

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2011
• First Posted: September 9, 2011
• Study Start: October 26, 2011
• Primary Completion: September 18, 2012
• Study Completion: October 1, 2012
• Last Updated: September 10, 2018
• Results First Posted: March 25, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share