Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8655 in Participants With Type 2 Diabetes (MK-8655-002) (NCT NCT01640873)

Last Updated: 2018-11-13

Results Overview

An adverse event 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

33 participants

Primary outcome timeframe

Up to 14 days after the last dose of study drug (Up to 31 days)

Results posted on

2018-11-13

Participant Flow

Participant was a male or female (of non-child bearing potential) between 18 to 65 years of age with a diagnosis of Type 2 diabetes mellitus (T2DM) and was either drug naïve or was being treated with metformin only.

Participant milestones

Participant milestones
Measure	MK-8655 80 mg/MK-8655 320 mg Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
Overall Study STARTED	22	11
Overall Study COMPLETED	20	10
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-8655 80 mg/MK-8655 320 mg Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
Overall Study Protocol Violation	2	1

Baseline Characteristics

All randomized participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-8655 80 mg/MK-8655 320 mg n=22 Participants Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo n=11 Participants Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Total n=33 Participants Total of all reporting groups
Age, Customized 31 to 63 years	22 Participants n=5 Participants	11 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants • All randomized participants	4 Participants n=7 Participants • All randomized participants	15 Participants n=5 Participants • All randomized participants
Sex: Female, Male Male	11 Participants n=5 Participants • All randomized participants	7 Participants n=7 Participants • All randomized participants	18 Participants n=5 Participants • All randomized participants

PRIMARY outcome

Timeframe: Up to 14 days after the last dose of study drug (Up to 31 days)

Population: All participants who received at least one dose of the investigational drug.

Outcome measures

Outcome measures
Measure	MK-8655 80 mg/MK-8655 320 mg n=22 Participants Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo n=11 Participants Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
Number of Participants With One or More Adverse Events	11 Participants	7 Participants

PRIMARY outcome

Timeframe: Up to 17 days

Population: All participants who received at least one dose of the investigational drug.

Outcome measures

Outcome measures
Measure	MK-8655 80 mg/MK-8655 320 mg n=22 Participants Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo n=11 Participants Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
Number of Participants Discontinuing Study Drug Due to an Adverse Event	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 16 (Predose)

Population: The analysis population was participants who complied with the protocol sufficiently to ensure that these data would likely exhibit the effects of treatment, according to the underlying scientific model. Compliance covered such considerations as exposure to treatment, availability of measurements and absence of major protocol violations.

Blood for fasting plasma glucose (central laboratory) was obtained after at least 10 hours overnight fast.

Outcome measures

Outcome measures
Measure	MK-8655 80 mg/MK-8655 320 mg n=22 Participants Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo n=11 Participants Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
Fasting Plasma Glucose (FPG)	195.5 mg/dL Standard Deviation 52.5	211.8 mg/dL Standard Deviation 70.2

SECONDARY outcome

Timeframe: 24 hours post dose on Days 1, 7, and 14

Population: The analysis population was participants who complied with the protocol sufficiently to ensure that these data would likely exhibit the effects of treatment, according to the underlying scientific model. No pharmacokinetic analysis for C24 was performed for participants receiving placebo.

C24hr was log transformed and analyzed based on a linear mixed effects model containing fixed effects for treatment, day and treatment by day interaction and a random effect for the participant.

Outcome measures

Outcome measures
Measure	MK-8655 80 mg/MK-8655 320 mg n=22 Participants Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
True Geometric Mean Plasma Concentrations of MK-8655 After Single and Multiple Drug Doses at 24 Hours Post Dose (C24) Day 1, MK-8655 80 mg, single dose	0.133 uM Geometric Coefficient of Variation 68.2	—
True Geometric Mean Plasma Concentrations of MK-8655 After Single and Multiple Drug Doses at 24 Hours Post Dose (C24) Day 1, MK-8655 320 mg, multiple doses	0.477 uM Geometric Coefficient of Variation 72.1	—
True Geometric Mean Plasma Concentrations of MK-8655 After Single and Multiple Drug Doses at 24 Hours Post Dose (C24) Day 7, MK-8655 320 mg, multiple doses	0.549 uM Geometric Coefficient of Variation 66.9	—
True Geometric Mean Plasma Concentrations of MK-8655 After Single and Multiple Drug Doses at 24 Hours Post Dose (C24) Day 14, MK-8655 320 mg, multiple doses	0.612 uM Geometric Coefficient of Variation 69.4	—

SECONDARY outcome

Timeframe: Day 15: Predose, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 18, 21, 23 hours post-dose.

The WMG provides an integrated assessment of the glycemic exposure over the 24-hour period. To reduce variability of the baseline (before any study drug administration) WMG, participants were domiciled in the test facility at least 36 hours prior to Day 1, where standard meals were provided, and physical activity was monitored. The WMG was derived from multiple glucose values collected during both fasting and post-meal periods. The sample scheme for the 18 point glucose measurements used in this study had many samples taken in the very early morning hours, as well as the first three hours after meals. WMG was calculated as the area under the curve (AUC) of the glucose concentrations divided by the duration of time of samples collected.

Outcome measures

Outcome measures
Measure	MK-8655 80 mg/MK-8655 320 mg n=22 Participants Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo n=11 Participants Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
24-Hour Weighted Mean Glucose (WMG)	205.5 mg/dL Standard Deviation 33.95	199.9 mg/dL Standard Deviation 78.81

SECONDARY outcome

Timeframe: Baseline and 2 hours after dosing on Days 1, 3, and 16

Plasma glucose excursion was assessed during an oral glucose tolerance test (oGTT) following a single dose administration of MK-8655 in participants with T2DM.

Outcome measures

Outcome measures
Measure	MK-8655 80 mg/MK-8655 320 mg n=22 Participants Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo n=11 Participants Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
Change From Baseline at 2 Hours Oral Glucose Tolerance Test Day 1	164.0 mg/dL Standard Deviation 41.4	134.7 mg/dL Standard Deviation 74.5
Change From Baseline at 2 Hours Oral Glucose Tolerance Test Day 3	162.3 mg/dL Standard Deviation 37.0	135.0 mg/dL Standard Deviation 74.1
Change From Baseline at 2 Hours Oral Glucose Tolerance Test Day 16	172.4 mg/dL Standard Deviation 39.2	156.1 mg/dL Standard Deviation 79.4

Adverse Events

MK-8655 80 mg/MK-8655 320 mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 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. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK-8655 80 mg/MK-8655 320 mg n=22 participants at risk Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.	Placebo n=11 participants at risk Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
Eye disorders Watering eyes	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	0.00% 0/11 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Gastrointestinal disorders Constipation	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	0.00% 0/11 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Gastrointestinal disorders Nausea	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	0.00% 0/11 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
General disorders Catheter site pain	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	0.00% 0/11 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
General disorders Tiredness	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	9.1% 1/11 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Infections and infestations Upper respiratory tract infection	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	9.1% 1/11 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Infections and infestations Urinary tract infection	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	0.00% 0/11 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Infections and infestations Viral upper respiratory tract infection	18.2% 4/22 • Number of events 4 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	27.3% 3/11 • Number of events 3 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Injury, poisoning and procedural complications Abrasion NOS	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	0.00% 0/11 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Investigations Ferritin decreased	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	9.1% 1/11 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Investigations Glucose increased	9.1% 2/22 • Number of events 2 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	9.1% 1/11 • Number of events 3 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Metabolism and nutrition disorders Hypoglycaemic reaction	0.00% 0/22 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	9.1% 1/11 • Number of events 4 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Musculoskeletal and connective tissue disorders Low back pain	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	0.00% 0/11 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Nervous system disorders Dizziness	9.1% 2/22 • Number of events 2 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	9.1% 1/11 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Nervous system disorders Headache	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	9.1% 1/11 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Psychiatric disorders Anxiety	0.00% 0/22 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	9.1% 1/11 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.
Respiratory, thoracic and mediastinal disorders Sore throat	4.5% 1/22 • Number of events 1 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.	0.00% 0/11 • Up to 31 days The analysis population was all participants who received at least one dose of the investigational drug.