Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK8245 (8245-004)(COMPLETED) (NCT NCT00790556)

Last Updated: 2016-02-17

Results Overview

An LAE is defined as any unfavorable \& unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A CAE is defined similarly but also includes changes in structure or function of the body. Serious AEs are those occuring that result in one or more of the pre-specified outcome(s) that meet the criteria of seriousness, including death, life-threatening, significant disability, or hospitalization, etc. Drug-relatedness was determined by the investigator based on clinical judgement.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

56 days

Results posted on

2016-02-17

Participant Flow

For subjects taking anti-hyperglycemic agents and who otherwise qualified for the study, a 4-week washout/run-in period was required prior to dosing.

Participant milestones

Participant milestones
Measure	MK8245 Then Placebo During Treatment Period 1, these subjects received MK-8245 50 mg twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. During Treatment Period 2, these subjects received MK-8245 matching placebo twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14.	Placebo Then MK8245 During Treatment Period 1, these subjects received MK-8245 matching placebo twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. During Treatment Period 2, these subjects received MK-8245 50 mg twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14.
Treatment Period 1 STARTED	8	6
Treatment Period 1 COMPLETED	6	6
Treatment Period 1 NOT COMPLETED	2	0
Washout After Period 1 STARTED	6	6
Washout After Period 1 COMPLETED	6	6
Washout After Period 1 NOT COMPLETED	0	0
Treatment Period 2 STARTED	6	6
Treatment Period 2 COMPLETED	6	6
Treatment Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	MK8245 Then Placebo During Treatment Period 1, these subjects received MK-8245 50 mg twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. During Treatment Period 2, these subjects received MK-8245 matching placebo twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14.	Placebo Then MK8245 During Treatment Period 1, these subjects received MK-8245 matching placebo twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. During Treatment Period 2, these subjects received MK-8245 50 mg twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14.
Treatment Period 1 Physician Decision	1	0
Treatment Period 1 Withdrawal by Subject	1	0

Baseline Characteristics

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK8245 (8245-004)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=14 Participants All participants
Age, Continuous	49.43 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 56 days

Population: All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).

Outcome measures

Outcome measures
Measure	MK8245 n=14 Participants MK-8245 50 mg twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. Includes results of this treatment from both treatment periods.	Placebo n=14 Participants MK-8245 matching placebo twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. Includes results of this treatment from both treatment periods.
Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) With clinical adverse events (CAEs)	4 participants	5 participants
Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) With drug-related CAEs	0 participants	0 participants
Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) With Serious CAEs	0 participants	0 participants
Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) With laboratory adverse events (LAEs)	0 participants	0 participants
Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) With drug-related LAEs	0 participants	0 participants
Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) With serious LAEs	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 14 of each 14-day Treatment Period

Population: Subjects who discontinued were not used in the analysis.

Changes in HGP were determined during a euglycemic clamp procedure. HGP was evaluated as milligrams per kilogram of glucose produced per minute.

Outcome measures

Outcome measures
Measure	MK8245 n=12 Participants MK-8245 50 mg twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. Includes results of this treatment from both treatment periods.	Placebo n=12 Participants MK-8245 matching placebo twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. Includes results of this treatment from both treatment periods.
Mean Change From Baseline in Hepatic Glucose Production (HGP) at Day 14	-1.09 mg/kg/min Standard Deviation 1.54	-0.87 mg/kg/min Standard Deviation 0.94

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: Subjects who discontinued were not used in the analysis.

Outcome measures

Outcome measures
Measure	MK8245 n=12 Participants MK-8245 50 mg twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. Includes results of this treatment from both treatment periods.	Placebo n=12 Participants MK-8245 matching placebo twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. Includes results of this treatment from both treatment periods.
Hepatic Glucose Production (HGP) at Baseline	1.87 mg/kg/min Standard Deviation 0.36	1.95 mg/kg/min Standard Deviation 0.36

Adverse Events

MK8245

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 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 Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK8245 n=14 participants at risk MK-8245 50 mg twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. Includes results of this treatment from both treatment periods.	Placebo n=14 participants at risk MK-8245 matching placebo twice daily 12 hours apart for 13 days, only the AM dose was administered on Day 14. Includes results of this treatment from both treatment periods.
Eye disorders Cataract	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Eye disorders Lacrimation increased	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Gastrointestinal disorders Flatulence	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
General disorders Chest pain	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
General disorders Chills	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
General disorders Feeling hot	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
General disorders Infusion site haemorrhage	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
General disorders Malaise	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Infections and infestations Body tinea	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Infections and infestations Cellulitis	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Infections and infestations Influenza	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Infections and infestations Oral herpes	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Musculoskeletal and connective tissue disorders Neck pain	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Nervous system disorders Headache	21.4% 3/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.00% 0/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).	7.1% 1/14 • Treatment Period 1, Days 1 to 14, 14 day washout, Treatment Period 2, Days 1 to 14, 14 days to post study. Spontaneous collection of all AEs; All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).