Trial Outcomes & Findings for Study of Changes in Hepatic Fat Following Administration of MK-4074 and Pioglitazone Hydrochloride (MK-4074-008) (NCT NCT01431521)

Last Updated: 2018-09-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

31 participants

Primary outcome timeframe

Up to 10 weeks

Results posted on

2018-09-10

Participant Flow

Thirty-one male or female participants (non-childbearing potential) between the ages of 18 and 60, inclusive, with body mass index (BMI) ≥ 32 kg/m\^2 were enrolled in the study. Participants were pre-screened by means of ultrasound, and only those participants with a rating of "moderate" or "severe" steatosis were further evaluated by means of MRI.

Participant milestones

Participant milestones
Measure	MK-4074 Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.	Placebo for MK-4074 Participants will receive oral doses of placebo to match MK-4074 twice daily for 4 weeks.	Pioglitazone Participants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks.	Placebo for Pioglitazone Participants will receive oral doses of placebo to match pioglitazone hydrochloride once daily for 4 weeks.
Overall Study STARTED	10	5	11	5
Overall Study Treated	10	5	10	5
Overall Study COMPLETED	10	5	10	5
Overall Study NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-4074 Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.	Placebo for MK-4074 Participants will receive oral doses of placebo to match MK-4074 twice daily for 4 weeks.	Pioglitazone Participants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks.	Placebo for Pioglitazone Participants will receive oral doses of placebo to match pioglitazone hydrochloride once daily for 4 weeks.
Overall Study Withdrawal by Subject	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-4074 n=10 Participants Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.	Placebo for MK-4074 n=5 Participants Participants will receive oral doses of placebo to match MK-4074 twice daily for 4 weeks.	Pioglitazone n=11 Participants Participants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks.	Placebo for Pioglitazone n=5 Participants Participants will receive oral doses of placebo to match pioglitazone hydrochloride once daily for 4 weeks.	Total n=31 Participants Total of all reporting groups
Age, Continuous	35.1 Years STANDARD_DEVIATION 5.8 • n=5 Participants	48.0 Years STANDARD_DEVIATION 7.6 • n=7 Participants	43.7 Years STANDARD_DEVIATION 12.1 • n=5 Participants	47.8 Years STANDARD_DEVIATION 10.6 • n=4 Participants	42.3 Years STANDARD_DEVIATION 10.5 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	7 Participants n=21 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants	1 Participants n=4 Participants	24 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: Per-Protocol (PP) Population consists of those participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model.

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.

Outcome measures

Outcome measures
Measure	MK-4074 n=10 Participants Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.	Pioglitazone n=10 Participants Participants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks.	Placebo n=10 Participants Participants will receive oral doses of placebo to match MK-4074 or pioglitazone hydrochloride once daily for 4 weeks.
Percent Change From Baseline in Hepatic Fat	-35.73 Percent change Interval -44.53 to -26.93	-18.04 Percent change Interval -26.84 to -9.24	8.63 Percent change Interval -0.17 to 17.43

PRIMARY outcome

Timeframe: Up to 10 weeks

Population: All Subjects as Treated (AST) Population consists of all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	MK-4074 n=10 Participants Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.	Pioglitazone n=10 Participants Participants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks.	Placebo n=10 Participants Participants will receive oral doses of placebo to match MK-4074 or pioglitazone hydrochloride once daily for 4 weeks.
Number of Participants Experiencing One or More Adverse Events (AE)	4 Participants	4 Participants	5 Participants

PRIMARY outcome

Timeframe: Up to 4 weeks

Population: The AST Population consists of all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	MK-4074 n=10 Participants Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.	Pioglitazone n=10 Participants Participants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks.	Placebo n=10 Participants Participants will receive oral doses of placebo to match MK-4074 or pioglitazone hydrochloride once daily for 4 weeks.
Number of Participants Who Discontinued Study Drug Due to an AE	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: The AST Population consists of all participants who received at least one dose of the study drug. One participant in the Placebo group did not have ALT data for Day 28.

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.

Outcome measures

Outcome measures
Measure	MK-4074 n=10 Participants Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.	Pioglitazone n=10 Participants Participants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks.	Placebo n=9 Participants Participants will receive oral doses of placebo to match MK-4074 or pioglitazone hydrochloride once daily for 4 weeks.
Percent Change From Baseline in Alanine Transaminase (ALT)	-9.82 Percent change Interval -21.13 to 1.49	-20.21 Percent change Interval -31.52 to -8.9	-3.47 Percent change Interval -15.08 to 8.13

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: The AST Population consists of all participants who received at least one dose of the study drug. One participant in the Placebo group did not have AST data for Day 28.

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.

Outcome measures

Outcome measures
Measure	MK-4074 n=10 Participants Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.	Pioglitazone n=10 Participants Participants will receive oral doses of pioglitazone hydrochloride 30 mg (1 x 30-mg tablet) once daily for 4 weeks.	Placebo n=9 Participants Participants will receive oral doses of placebo to match MK-4074 or pioglitazone hydrochloride once daily for 4 weeks.
Percent Change From Baseline Aspartate Transaminase (AST)	-6.74 Percent change Interval -19.73 to 6.24	-13.95 Percent change Interval -26.93 to -0.97	-3.28 Percent change Interval -16.64 to 10.08

Adverse Events

MK-4074

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo for MK-4074

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Pioglitazone

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo for Pioglitazone

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/ presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK-4074 n=10 participants at risk Participants will receive oral doses of MK-4074 200 mg (2 x 100-mg capsules) twice daily for 4 weeks.	Placebo for MK-4074 n=5 participants at risk Participants will receive oral doses of placebo matching MK-4074 twice daily for 4 weeks.	Pioglitazone n=10 participants at risk Participants will receive oral doses of pioglitazone hydrochloride 30 mg once daily for 4 weeks.	Placebo for Pioglitazone n=5 participants at risk Participants will receive oral doses of placebo to match pioglitazone hydrochloride once daily for 4 weeks.
Infections and infestations Upper respiratory tract infection	20.0% 2/10 • Number of events 2 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Injury, poisoning and procedural complications Burns first degree	10.0% 1/10 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	10.0% 1/10 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	10.0% 1/10 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Nervous system disorders Dizziness	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	10.0% 1/10 • Number of events 2 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Nervous system disorders Dysgeusia	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	10.0% 1/10 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Nervous system disorders Headache	10.0% 1/10 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 2/10 • Number of events 4 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 3 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Nervous system disorders Migraine	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Psychiatric disorders Anxiety	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	10.0% 1/10 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Eye disorders Eyelids pruritus	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Gastrointestinal disorders Vomiting	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 2/10 • Number of events 2 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
General disorders Thirst	10.0% 1/10 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Infections and infestations Sinusitis	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	20.0% 1/5 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.
Infections and infestations Tooth infection	10.0% 1/10 • Number of events 1 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/10 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.	0.00% 0/5 • Up to 10 weeks The AST Population (Safety Population) consists of all participants who received at least one dose of the study drug.