Diabetes Mellitus, Type 2
Conditions
Brief summary
A study to compare MK0893 to metformin or placebo for patients with Type 2 diabetes (Diabetes Mellitus).
Interventions
DRUGMK0893
MK0893 taken orally once daily; 20 mg and 40 mg tablets used in combination according to dose.
DRUGMetformin
Metformin HCL 500 mg tablet twice daily titrating up to 1000 mg twice daily over 3 weeks.
DRUGPlacebo to MK0893
Dose-matched placebo tablets to MK0893; taken orally once daily.
Dose-matched placebo tablets to metformin (500 mg); taken orally twice daily.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have Type 2 Diabetes Mellitus, with suboptimal glucose control, while either not on AHA (antihyperglycemic agent) therapy or on monotherapy or on low-dose combination therapy
Exclusion criteria
* Patients have a history of Type 1 Diabetes Mellitus * Patients taking insulin or thiazolidinedione (TZD, a peroxisome proliferator-activated receptor \[PPAR\]-gamma agonist) * Patients who have a contraindication to metformin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) | Week 12 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) | Week 12 |
| Change From Baseline to Week 12 in 2-Hour Post Prandial Glucose (PPG) | Week 12 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo | 57 |
| MK0893 20 mg | 57 |
| MK0893 40 mg | 57 |
| MK0893 60 mg | 58 |
| MK0893 80 mg | 56 |
| Metformin HCL | 57 |
| Total | 342 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 1 | 0 | 1 | 2 | 0 |
| Overall Study | Hyperglycemia | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 2 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 | 2 | 2 |
| Overall Study | Physician Decision | 2 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 5 | 0 | 2 | 3 | 1 |
Baseline characteristics
| Characteristic | Placebo | MK0893 20 mg | MK0893 40 mg | MK0893 60 mg | MK0893 80 mg | Metformin HCL | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.1 years STANDARD_DEVIATION 10.2 | 55.6 years STANDARD_DEVIATION 8.2 | 53.7 years STANDARD_DEVIATION 8.2 | 56.1 years STANDARD_DEVIATION 7.9 | 53.5 years STANDARD_DEVIATION 10.4 | 55.1 years STANDARD_DEVIATION 8.2 | 54.7 years STANDARD_DEVIATION 8.9 |
| Sex: Female, Male Female | 31 Participants | 28 Participants | 22 Participants | 26 Participants | 31 Participants | 30 Participants | 168 Participants |
| Sex: Female, Male Male | 26 Participants | 29 Participants | 35 Participants | 32 Participants | 25 Participants | 27 Participants | 174 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 57 | 11 / 57 | 22 / 57 | 16 / 58 | 12 / 56 | 13 / 57 |
| serious Total, serious adverse events | 5 / 57 | 0 / 57 | 1 / 57 | 0 / 58 | 2 / 56 | 0 / 57 |
Outcome results
Primary
Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG)
Time frame: Week 12
Population: All participants who received at least one dose of study therapy, had a baseline measurement, and had at least one post-randomization measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) | -1.8 mg/dL |
| MK0893 20 mg | Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) | -32.4 mg/dL |
| MK0893 40 mg | Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) | -48.4 mg/dL |
| MK0893 60 mg | Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) | -53.0 mg/dL |
| MK0893 80 mg | Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) | -63.0 mg/dL |
| Metformin HCL | Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) | -37.3 mg/dL |
p-value: <0.00195% CI: [-44, -17.3]ANCOVA
p-value: <0.00195% CI: [-59.7, -33.4]ANCOVA
p-value: <0.00195% CI: [-64.3, -38]ANCOVA
p-value: <0.00195% CI: [-74.6, -47.8]ANCOVA
p-value: <0.00195% CI: [-48.6, -22.4]ANCOVA
Secondary
Change From Baseline to Week 12 in 2-Hour Post Prandial Glucose (PPG)
Time frame: Week 12
Population: All participants who received at least one dose of study therapy, had a baseline measurement, and had at least one post-randomization measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 12 in 2-Hour Post Prandial Glucose (PPG) | -8.1 mg/dL |
| MK0893 20 mg | Change From Baseline to Week 12 in 2-Hour Post Prandial Glucose (PPG) | -64.9 mg/dL |
| MK0893 40 mg | Change From Baseline to Week 12 in 2-Hour Post Prandial Glucose (PPG) | -78.1 mg/dL |
| MK0893 60 mg | Change From Baseline to Week 12 in 2-Hour Post Prandial Glucose (PPG) | -95.5 mg/dL |
| MK0893 80 mg | Change From Baseline to Week 12 in 2-Hour Post Prandial Glucose (PPG) | -109.7 mg/dL |
| Metformin HCL | Change From Baseline to Week 12 in 2-Hour Post Prandial Glucose (PPG) | -68.9 mg/dL |
p-value: <0.00195% CI: [-79.4, -34.3]ANCOVA
p-value: <0.00195% CI: [-91.8, -48.2]ANCOVA
p-value: <0.00195% CI: [-109.4, -65.3]ANCOVA
p-value: <0.00195% CI: [-124.2, -79.1]ANCOVA
p-value: <0.00195% CI: [-82.7, -38.8]ANCOVA
Secondary
Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c)
Time frame: Week 12
Population: All participants who received at least one dose of study therapy, had a baseline measurement, and had at least one post-randomization measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) | 0.54 mg/dL |
| MK0893 20 mg | Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) | -0.60 mg/dL |
| MK0893 40 mg | Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) | -0.99 mg/dL |
| MK0893 60 mg | Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) | -1.14 mg/dL |
| MK0893 80 mg | Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) | -1.52 mg/dL |
| Metformin HCL | Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) | -0.78 mg/dL |
p-value: <0.00195% CI: [-1.53, -0.76]ANCOVA
p-value: <0.00195% CI: [-1.91, -1.15]ANCOVA
p-value: <0.00195% CI: [-2.07, -1.31]ANCOVA
p-value: <0.00195% CI: [-2.45, -1.68]ANCOVA
p-value: <0.00195% CI: [-1.7, -0.95]ANCOVA