Trial Outcomes & Findings for Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Participants With Type 2 Diabetes Mellitus (MK-8666-003) (NCT NCT01971554)
NCT ID: NCT01971554
Last Updated: 2018-09-10
Results Overview
Blood glucose was measured on a fasting basis (collected after an 8-hour fast). Blood was collected on Day -1 (pre-planned dose), predose on Days 1, 3, 7, and 14, and 24h postdose Day 14 (Day 15). The baseline measurement was computed as the average of the Day -1 and predose Day 1 measurements. FPG is expressed as mg/dL. This change from baseline reflects values for Day 15 FPG minus Day 0 FPG values.
COMPLETED
PHASE1
63 participants
Predose (Baseline) and 24 h postdose Day 14 (Day 15)
2018-09-10
Participant Flow
Sixty-three participants were recruited at 4 clinical sites in the United States.
Male and female participants with Type 2 diabetes mellitus between the ages of 18 and 65 years inclusive were enrolled in this trial.
Participant milestones
| Measure |
MK-8666 50 mg
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
18
|
18
|
18
|
|
Overall Study
COMPLETED
|
8
|
18
|
18
|
18
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
MK-8666 50 mg
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of MK-8666 in Participants With Type 2 Diabetes Mellitus (MK-8666-003)
Baseline characteristics by cohort
| Measure |
MK-8666 50 mg
n=9 Participants
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
n=18 Participants
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
n=18 Participants
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
n=18 Participants
Placebo once daily for 14 consecutive days
|
Total
n=63 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
53.9 Years
FULL_RANGE 10.0 • n=5 Participants
|
55.6 Years
FULL_RANGE 6.2 • n=7 Participants
|
55.2 Years
FULL_RANGE 6.9 • n=5 Participants
|
54.7 Years
FULL_RANGE 8.3 • n=4 Participants
|
55.0 Years
n=21 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
38 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Predose (Baseline) and 24 h postdose Day 14 (Day 15)Population: The Per-Protocol population is the subset of participants who complied with the protocol sufficiently to ensure that these data are likely to exhibit the effects of treatment, according to the underlying scientific model.
Blood glucose was measured on a fasting basis (collected after an 8-hour fast). Blood was collected on Day -1 (pre-planned dose), predose on Days 1, 3, 7, and 14, and 24h postdose Day 14 (Day 15). The baseline measurement was computed as the average of the Day -1 and predose Day 1 measurements. FPG is expressed as mg/dL. This change from baseline reflects values for Day 15 FPG minus Day 0 FPG values.
Outcome measures
| Measure |
MK-8666 50 mg
n=9 Participants
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
n=18 Participants
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
n=18 Participants
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
n=18 Participants
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 15
|
32.8 mg/dL
Standard Error 9.7
|
37.9 mg/dL
Standard Error 7.0
|
56.0 mg/dL
Standard Error 7.0
|
2.0 mg/dL
Standard Error 7.0
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: The Safety population consisted of all participants who received at least one dose of study medication.
An adverse event (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.
Outcome measures
| Measure |
MK-8666 50 mg
n=9 Participants
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
n=18 Participants
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
n=18 Participants
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
n=18 Participants
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Number of Participants Who Experienced at Least Once Adverse Event
|
3 Participants
|
9 Participants
|
10 Participants
|
5 Participants
|
PRIMARY outcome
Timeframe: Up to 14 daysPopulation: The Safety population consisted of all participants who received at least one dose of study medication.
An adverse event (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.
Outcome measures
| Measure |
MK-8666 50 mg
n=9 Participants
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
n=18 Participants
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
n=18 Participants
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
n=18 Participants
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Number of Participants Who Discontinued Study Drug Due to an AE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdosePopulation: The Per-Protocol population is the subset of participants who complied with the protocol sufficiently to ensure that these data are likely to exhibit the effects of treatment, according to the underlying scientific model. Pharmacokinetic testing was not performed on the Placebo group.
AUC0-last is a measure of the total amount of drug in the plasma from the dose to 24 hours after the dose of study drug. Pharmacokinetic parameter analysis was not performed on the Placebo group. Method of dispersion for AUC0-24h was geometric mean coefficient of variation percentage.
Outcome measures
| Measure |
MK-8666 50 mg
n=9 Participants
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
n=18 Participants
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
n=18 Participants
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)
Day 1
|
6.11 μM·hr
Geometric Coefficient of Variation 88
|
37.2 μM·hr
Geometric Coefficient of Variation 44
|
143 μM·hr
Geometric Coefficient of Variation 33
|
—
|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)
Day 14
|
15.3 μM·hr
Geometric Coefficient of Variation 88
|
66.9 μM·hr
Geometric Coefficient of Variation 32
|
172 μM·hr
Geometric Coefficient of Variation 37
|
—
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdosePopulation: The Per-Protocol population is the subset of participants who complied with the protocol sufficiently to ensure that these data are likely to exhibit the effects of treatment, according to the underlying scientific model. Pharmacokinetic testing was not performed on the Placebo group.
Cmax is a measure of the maximum amount of drug in the plasma after the dose of study drug. Pharmacokinetic parameter analysis was not performed on the Placebo group. Method of dispersion for Cmax was geometric mean coefficient of variation percentage.
Outcome measures
| Measure |
MK-8666 50 mg
n=9 Participants
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
n=18 Participants
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
n=18 Participants
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Maximum Plasma Drug Concentration After Dosing (Cmax)
Day 1
|
0.906 μM
Geometric Coefficient of Variation 102
|
4.49 μM
Geometric Coefficient of Variation 45
|
17.1 μM
Geometric Coefficient of Variation 40
|
—
|
|
Maximum Plasma Drug Concentration After Dosing (Cmax)
Day 14
|
1.50 μM
Geometric Coefficient of Variation 93
|
7.16 μM
Geometric Coefficient of Variation 37
|
19.9 μM
Geometric Coefficient of Variation 32
|
—
|
SECONDARY outcome
Timeframe: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, and 24 hours postdose; Day 14 : Predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours postdosePopulation: The Per-Protocol population is the subset of participants who complied with the protocol sufficiently to ensure that these data are likely to exhibit the effects of treatment, according to the underlying scientific model. Pharmacokinetic testing was not performed on the Placebo group.
Tmax is a measure of the time to reach the maximum concentration in the plasma after the dose of study drug. Pharmacokinetic parameter analysis was not performed on the Placebo group.
Outcome measures
| Measure |
MK-8666 50 mg
n=9 Participants
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
n=18 Participants
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
n=18 Participants
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Time to Reach Cmax (Tmax)
Day 1
|
2.0 hr
Interval 1.5 to 12.0
|
2.25 hr
Interval 1.5 to 4.0
|
2.5 hr
Interval 1.5 to 8.0
|
—
|
|
Time to Reach Cmax (Tmax)
Day 14
|
2.0 hr
Interval 1.0 to 12.0
|
2.0 hr
Interval 1.0 to 6.0
|
2.0 hr
Interval 0.5 to 3.0
|
—
|
SECONDARY outcome
Timeframe: Baseline and Day 15Population: The Per-Protocol population is the subset of participants who complied with the protocol sufficiently to ensure that these data are likely to exhibit the effects of treatment, according to the underlying scientific model. Data from 1 participant at Day 14 (Placebo group) was missing as the participant had to leave the study site.
The 24h-WMG was considered to provide an integrated assessment of the glycemic exposure over the 24-hour period, and was derived from 18 blood samples collected immediately prior to, and after each meal, and overnight and fasting one hour pre-dose. A "weighted" rather than a "simple" mean is used to avoid overrepresentation of post-meal glucose values. On each day (Day -1 and Day 14), the WMG was computed as a time-weighted average of the 18 individual measurements.
Outcome measures
| Measure |
MK-8666 50 mg
n=9 Participants
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
n=18 Participants
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
n=18 Participants
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
n=17 Participants
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Change From Baseline in 24-Hour Weighted Mean Glucose (24h-WMG) at Day 15
|
19.0 mg/dL
Standard Error 7.9
|
27.3 mg/dL
Standard Error 5.7
|
45.4 mg/dL
Standard Error 5.7
|
-3.3 mg/dL
Standard Error 5.8
|
Adverse Events
MK-8666 50 mg
MK-8666 150 mg
MK-8666 500 mg
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
MK-8666 50 mg
n=9 participants at risk
MK-8666 50 mg once daily for 14 consecutive days
|
MK-8666 150 mg
n=18 participants at risk
MK-8666 150 mg once daily for 14 consecutive days
|
MK-8666 500 mg
n=18 participants at risk
MK-8666 500 mg once daily for 14 consecutive days
|
Placebo
n=18 participants at risk
Placebo once daily for 14 consecutive days
|
|---|---|---|---|---|
|
Cardiac disorders
Bundle branch block right
|
0.00%
0/9 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Eye disorders
Eye irritation
|
11.1%
1/9 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Eye disorders
Eye redness
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Eye disorders
Vision blurred
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
11.1%
2/18 • Number of events 2 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Gastrointestinal disorders
Abdominal cramp
|
11.1%
1/9 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 2 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Gastrointestinal disorders
Constipation
|
11.1%
1/9 • Number of events 1 • Up to 28 days
|
16.7%
3/18 • Number of events 3 • Up to 28 days
|
16.7%
3/18 • Number of events 4 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 2 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
|
Gastrointestinal disorders
Loose stools
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
11.1%
2/18 • Number of events 2 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Gastrointestinal disorders
Nausea
|
11.1%
1/9 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
16.7%
3/18 • Number of events 4 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
|
General disorders
Fatigue
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Injury, poisoning and procedural complications
Contusion of upper limb
|
0.00%
0/9 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/9 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
0.00%
0/9 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
5.6%
1/18 • Number of events 2 • Up to 28 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/9 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
11.1%
2/18 • Number of events 2 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Musculoskeletal and connective tissue disorders
Low back pain
|
0.00%
0/9 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/9 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Musculoskeletal and connective tissue disorders
Pain in foot
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Musculoskeletal and connective tissue disorders
Pain in leg
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Musculoskeletal and connective tissue disorders
Shoulder pain
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 3 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
|
Nervous system disorders
Drowsiness
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Nervous system disorders
Drug-induced headache
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Nervous system disorders
Headache
|
22.2%
2/9 • Number of events 2 • Up to 28 days
|
11.1%
2/18 • Number of events 2 • Up to 28 days
|
16.7%
3/18 • Number of events 4 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Nervous system disorders
Occipital headache
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Renal and urinary disorders
Urine discolouration
|
11.1%
1/9 • Number of events 1 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/9 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
0.00%
0/18 • Up to 28 days
|
5.6%
1/18 • Number of events 1 • Up to 28 days
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
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 trial 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
- Publication restrictions are in place
Restriction type: OTHER