Non-alcoholic Fatty Liver DiseasePhase 1NCT01431521
Study of Changes in Hepatic Fat Following Administration of MK-4074 and Pioglitazone Hydrochloride (MK-4074-008)
A Phase 1 study testing MK-4074 200 mg and Pioglitazone hydrochloride 30 mg in people with Non-alcoholic Fatty Liver Disease, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- MK-4074 200 mg and Pioglitazone hydrochloride 30 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- No sites listed yet
- Study dates
- 26 Oct 2011to 1 Oct 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
About this study
Official title: An Exploratory Study to Evaluate Changes in Hepatic Fat Following Multiple-Dose Administration of MK-4074 and Pioglitazone Hydrochloride
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
- Being tested
- MK-4074 200 mg, Placebo for MK-4074, Pioglitazone hydrochloride 30 mg, Placebo for pioglitazone hydrochloride
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-4074 200 mgDrug
2 x 100-mg capsules, orally, twice-daily (BID) for 4 weeks
Placebo for MK-4074Drug
2 x 100-mg capsules, orally, BID for 4 weeks.
Pioglitazone hydrochloride 30 mgDrug
1 x 30-mg tablet, orally, once daily for 4 weeks
Placebo for pioglitazone hydrochlorideDrug
1 x 30-mg tablet, orally, once daily for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| MK-4074 | Experimental | Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo for pioglitazone hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to 4 weeks
Secondary outcomes (2)
Percent Change From Baseline in Alanine Transaminase (ALT)
Hepatic steatosis is not uncommonly associated with mild elevations in serum transaminases, specifically ALT, and these elevations may be a marker of more advanced hepatic disease. Serum transaminases were monitored at baseline and once weekly for the duration of the study to permit a better understanding of the time course of potential improvement in hepatic inflammation during the course of this short study.
Measured: Baseline and Week 4
Percent Change From Baseline Aspartate Transaminase (AST)
Hepatic steatosis is not uncommonly associated with mild elevations in serum transaminases, including AST, and these elevations may be a marker of more advanced hepatic disease. Serum transaminases were monitored at baseline and once weekly for the duration of the study to permit a better understanding of the time course of potential improvement in hepatic inflammation during the course of this short study.
Measured: Baseline and Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2011 (estimated)
- Study start26 Oct 2011
- Primary completion18 Sep 2012
- Study completion1 Oct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01431521
- Sponsor's protocol ID
- 4074-008
- Status last verified
- Aug 2018
- First submitted
- 7 Sep 2011
- Last updated
- 10 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study to Evaluate Changes in Hepatic Fat Following Multiple-Dose Administration of MK-4074 and Pioglitazone Hydrochloride
- ClinicalTrials.gov ID
- NCT01431521
- Acronym / sponsor ID
- 4074-008
- Conditions
- Non-alcoholic Fatty Liver Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 26 Oct 2011 (actual)
- Primary completion
- 18 Sep 2012 (actual)
- Study completion
- 1 Oct 2012 (actual)
- First posted
- 9 Sep 2011 (estimated)
- Results
- Posted 25 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MK-4074 | Experimental | Drug: MK-4074 200 mgParticipants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks. |
| Placebo for MK-4074 | Placebo comparator | Drug: Placebo for MK-4074Participants will receive oral doses of placebo to match MK-4074 twice daily for 4 weeks. |
| Pioglitazone | Experimental | Drug: Pioglitazone hydrochloride 30 mgParticipants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks. |
| Placebo for pioglitazone | Placebo comparator | Drug: Placebo for pioglitazone hydrochlorideParticipants will receive oral doses of placebo to match pioglitazone hydrochloride once daily for 4 weeks. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-4074 200 mg2 x 100-mg capsules, orally, twice-daily (BID) for 4 weeks | Drug | MK-4074 |
| Placebo for MK-40742 x 100-mg capsules, orally, BID for 4 weeks. | Drug | Placebo for MK-4074 |
| Pioglitazone hydrochloride 30 mg1 x 30-mg tablet, orally, once daily for 4 weeks | Drug | Pioglitazone |
| Placebo for pioglitazone hydrochloride1 x 30-mg tablet, orally, once daily for 4 weeks | Drug | Placebo for pioglitazone |
Primary outcome
Percent Change From Baseline in Hepatic Fat
Time frame: Baseline and Week 4
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.
Number of Participants Experiencing One or More Adverse Events (AE)
Time frame: Up to 10 weeks
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.
Number of Participants Who Discontinued Study Drug Due to an AE
Time frame: Up to 4 weeks
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.
2 secondary outcomes
Percent Change From Baseline in Alanine Transaminase (ALT)
Time frame: Baseline and Week 4
Percent Change From Baseline Aspartate Transaminase (AST)
Time frame: Baseline and Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-4074 200 mg and Pioglitazone hydrochloride 30 mg in people with Non-alcoholic Fatty Liver Disease, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Hepatic Fat (time frame: Baseline and Week 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2018.