Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to test the effect of MK-0941 as add-on therapy for participants taking metformin for type 2 diabetes.
Interventions
DRUGMK-0941
MK-0941 will be taken three times a day (TID), within 15 minutes before each meal. MK-0941 will be titrated to a maximally effective dose. The treatment period will be 6 weeks.
DRUGGlimepiride
Glimepiride will be taken once a day (QD) in the morning, within 15 minutes before the breakfast meal. Glimepiride will be titrated to a maximally effective dose. The treatment period is 6 weeks.
DRUGMetformin
The study will include an up to 4-week metformin dose titration/dose stabilization period. Once a participant has reached the maximum tolerated dose of metformin \[(i.e., ≥1500 mg/day and ≤2550 mg/day (or ≤3000 mg/day, where the maximum dose of metformin per the local label is 3000 mg/day)\], the participant should remain on the same metformin dose throughout the study.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patient has type 2 diabetes mellitus * Between the ages of 18 and 70
Exclusion criteria
* Patient has a history of type 1 diabetes mellitus or ketoacidosis. * Patient is on a weight loss program and is not in the maintenance phase or is taking weight loss medication. * Patient has had surgery within 30 days of starting the study or has planned major surgery during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in 24-hour Weighted Mean Glucose | Baseline and Week 6 | Weighted Mean Glucose (WMG) is a measure of the amount of glucose in the blood over a period of 24 hours. The WMG was derived from multiple glucose values collected during both fasting and post-meal periods. The weighted mean was used to avoid over-representation of post-meal glucose values. |
| Number of Participants Who Experienced One or More Episodes of Hypoglycemia (Symptomatic or Asymptomatic) | Baseline to Week 6 | Hypoglycemic episodes are defined as either a fingerstick glucose measurement of ≤70 mg/dL \[3.9 mmol/L\] with or without symptoms or symptomatic hypoglycemia. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-0941 Participants receive MK-0941 5 mg or 10 mg tablets, orally, TID and placebo tablets matching glimepiride 1 mg or 2 mg, orally, QD for 6 weeks. Up-titration and down-titration of the dose could occur to achieve optimal individual glucose control. In addition, all participants received a maximum tolerated dose of metformin \[(i.e., ≥1500 mg/day and ≤2550 mg/day (or ≤3000 mg/day, where the maximum dose of metformin per the local label is 3000 mg/day)\], after a 4-week dose titration/dose stabilization period. | 72 |
| Glimepiride Participants receive glimepiride 1 mg or 2 mg tablets, orally, QD and placebo tablets matching MK-0941 5 mg or 10 mg, orally, TID for 6 weeks. Up-titration and down-titration of the dose could occur to achieve optimal individual glucose control. In addition, all participants received a maximum tolerated dose of metformin \[(i.e., ≥1500 mg/day and ≤2550 mg/day (or ≤3000 mg/day, where the maximum dose of metformin per the local label is 3000 mg/day)\], after a 4-week dose titration/dose stabilization period. | 71 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | MK-0941 | Glimepiride | Total |
|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 9.5 | 55.2 years STANDARD_DEVIATION 9.8 | 55 years STANDARD_DEVIATION 9.6 |
| Mean 24-Hour Weighted Mean Glucose at Baseline | 178.8 mg/dL STANDARD_DEVIATION 33.9 | 184.4 mg/dL STANDARD_DEVIATION 38.4 | 181.6 mg/dL STANDARD_DEVIATION 36.2 |
| Sex: Female, Male Female | 29 Participants | 26 Participants | 55 Participants |
| Sex: Female, Male Male | 43 Participants | 45 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 72 | 25 / 71 |
| serious Total, serious adverse events | 1 / 72 | 1 / 71 |
Outcome results
Primary
Change From Baseline to Week 6 in 24-hour Weighted Mean Glucose
Weighted Mean Glucose (WMG) is a measure of the amount of glucose in the blood over a period of 24 hours. The WMG was derived from multiple glucose values collected during both fasting and post-meal periods. The weighted mean was used to avoid over-representation of post-meal glucose values.
Time frame: Baseline and Week 6
Population: The full analysis set (FAS) population included all randomized participants who had efficacy measurements at baseline or a post-randomization visit).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0941 | Change From Baseline to Week 6 in 24-hour Weighted Mean Glucose | -43.4 mg/dL |
| Glimepiride | Change From Baseline to Week 6 in 24-hour Weighted Mean Glucose | -44.2 mg/dL |
Comparison: Using a standard deviation of 23.5 mg/dL, a sample size of at least 65 participants per treatment group would be required to have an 80% power to detect a true difference of 12.5 mg/dL between MK-0941 and glimepiride as measured by change from baseline in 24-hour WMG at Week 6.p-value: 0.84795% CI: [-7.9, 9.6]Constrained longitudinal analysis
Primary
Number of Participants Who Experienced One or More Episodes of Hypoglycemia (Symptomatic or Asymptomatic)
Hypoglycemic episodes are defined as either a fingerstick glucose measurement of ≤70 mg/dL \[3.9 mmol/L\] with or without symptoms or symptomatic hypoglycemia.
Time frame: Baseline to Week 6
Population: All patients as treated (APaT) defined as all randomized participants who received at least one dose of MK-0941 or glimepiride.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0941 | Number of Participants Who Experienced One or More Episodes of Hypoglycemia (Symptomatic or Asymptomatic) | 32 participants |
| Glimepiride | Number of Participants Who Experienced One or More Episodes of Hypoglycemia (Symptomatic or Asymptomatic) | 37 participants |
p-value: 0.36195% CI: [-23.6, 8.7]Miettinen & Nurminen method.