Type 2 Diabetes Mellitus
Conditions
Brief summary
A study to evaluate the efficacy and safety of MK0431A in comparison to a commonly used medication in patients with type 2 diabetes
Interventions
sitagliptin phosphate (+) metformin hydrochloride 50/500 mg tablet bid, titrating up to sitagliptin phosphate (+) metformin hydrochloride 50/1000 mg tablet for an \ 32 wk treatment period
pioglitazone 30 mg tablet qd, titrating up to 45 mg qd for an \ 32-wk treatment period.
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 78 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: * Patient has type 2 diabetes mellitus * Patient is inadequately controlled and not on treatment with insulin or oral antihyperglycemic therapy General
Exclusion criteria
* Patient has a history of type 1 diabetes mellitus or history of ketoacidosis * Patient was on antihyperglycemic agent therapy (oral or insulin) within the prior 12 weeks * Patient was on \>4 weeks (cumulatively) of antihyperglycemic therapy (oral or insulin) over the prior 3 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in A1C at Week 32 | Baseline and Week 32 | A1C is measured as a percent. Thus this change from baseline reflects the Week 32 A1C percent minus the baseline A1C percent |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 1 | Baseline and Week 1 | Change from baseline reflects the Week 1 FPG minus the baseline FPG. At Week 1, the dose was 50/500 mg b.i.d. for Sita/Met FDC and 30 mg q.d. for pioglitazone |
| Change From Baseline in 2-hour Post-Meal Glucose (PMG) at Week 32 | Baseline and Week 32 | Change from baseline reflects the Week 32 2-hour PMG minus the baseline 2-hour PMG |
| Change From Baseline in FPG at Week 32 | Baseline and Week 32 | Change from baseline reflects the Week 32 FPG minus the baseline FPG |
| Percent of Participants With A1C <7.0% at Week 32 | Week 32 | — |
Participant flow
Recruitment details
First Patient In: 19-Mar-2008 Last Patient Last Visit: 23-Oct-2009 Seventy-four medical clinics worldwide (19 sites in the United States, 31 in Eastern Europe, and 24 in the rest of the world).
Pre-assignment details
Patients 18-78 years old with Type 2 Diabetes Mellitus (T2DM), drug-naïve (off antihyperglycemic agent \[AHA\] for at least 3 months prior to screening, and a maximum 4 weeks cumulative AHA therapy over the previous 3 years), hemoglobin A1C 7.5 to 12% were eligible. Eligible patients underwent a 2-week placebo run-in period prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin/Metformin Fixed-Dose Combination The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose. | 261 |
| Pioglitazone The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose. | 256 |
| Total | 517 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 12 |
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | Lost to Follow-up | 10 | 6 |
| Overall Study | Physician Decision | 4 | 5 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Specific Criteria | 11 | 15 |
| Overall Study | Protocol Violation | 4 | 2 |
| Overall Study | Withdrawal by Subject | 10 | 9 |
Baseline characteristics
| Characteristic | Total | Pioglitazone | Sitagliptin/Metformin Fixed-Dose Combination |
|---|---|---|---|
| 2-Hour Post-Meal Glucose (2-HR PMG) | 276.2 mg/dL STANDARD_DEVIATION 85.5 | 278.8 mg/dL STANDARD_DEVIATION 86.4 | 273.7 mg/dL STANDARD_DEVIATION 84.8 |
| Age, Continuous | 52.3 years STANDARD_DEVIATION 10.8 | 52.2 years STANDARD_DEVIATION 11 | 52.4 years STANDARD_DEVIATION 10.7 |
| Fasting Plasma Glucose (FPG) | 189.8 mg/dL STANDARD_DEVIATION 55.2 | 188.9 mg/dL STANDARD_DEVIATION 57.1 | 190.6 mg/dL STANDARD_DEVIATION 53.4 |
| Hemoglobin A1C (A1C) | 8.9 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 1.3 | 8.9 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 1.3 | 9.0 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 1.3 |
| Race/Ethnicity, Customized American Indian | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 113 participants | 55 participants | 58 participants |
| Race/Ethnicity, Customized Black | 11 participants | 5 participants | 6 participants |
| Race/Ethnicity, Customized Multi-racial | 56 participants | 29 participants | 27 participants |
| Race/Ethnicity, Customized White | 335 participants | 167 participants | 168 participants |
| Sex: Female, Male Female | 240 Participants | 122 Participants | 118 Participants |
| Sex: Female, Male Male | 277 Participants | 134 Participants | 143 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 94 / 261 | 68 / 256 |
| serious Total, serious adverse events | 11 / 261 | 8 / 256 |
Outcome results
Primary
Change From Baseline in A1C at Week 32
A1C is measured as a percent. Thus this change from baseline reflects the Week 32 A1C percent minus the baseline A1C percent
Time frame: Baseline and Week 32
Population: The Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome. For FAS patients with no data at Week 32, the last non-baseline observed measurement was carried forward to Week 32.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin Fixed-Dose Combination | Change From Baseline in A1C at Week 32 | -1.86 Percent of glycosylated hemoglobin (A1C) |
| Pioglitazone | Change From Baseline in A1C at Week 32 | -1.39 Percent of glycosylated hemoglobin (A1C) |
p-value: <0.00195% CI: [-0.66, -0.28]ANCOVA
Secondary
Change From Baseline in 2-hour Post-Meal Glucose (PMG) at Week 32
Change from baseline reflects the Week 32 2-hour PMG minus the baseline 2-hour PMG
Time frame: Baseline and Week 32
Population: The Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome. For FAS patients with no data at Week 32, the last non-baseline observed measurement was carried forward to Week 32.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin Fixed-Dose Combination | Change From Baseline in 2-hour Post-Meal Glucose (PMG) at Week 32 | -102.2 mg/dL |
| Pioglitazone | Change From Baseline in 2-hour Post-Meal Glucose (PMG) at Week 32 | -82.0 mg/dL |
p-value: <0.00195% CI: [-32.1, -8.3]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 1
Change from baseline reflects the Week 1 FPG minus the baseline FPG. At Week 1, the dose was 50/500 mg b.i.d. for Sita/Met FDC and 30 mg q.d. for pioglitazone
Time frame: Baseline and Week 1
Population: The Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin Fixed-Dose Combination | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 1 | -40.5 mg/dL |
| Pioglitazone | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 1 | -13.0 mg/dL |
p-value: <0.00195% CI: [-32.7, -22.4]ANCOVA
Secondary
Change From Baseline in FPG at Week 32
Change from baseline reflects the Week 32 FPG minus the baseline FPG
Time frame: Baseline and Week 32
Population: Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome. For FAS patients with no data at Week 32, the last non-baseline observed measurement was carried forward to Week 32.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin Fixed-Dose Combination | Change From Baseline in FPG at Week 32 | -56.0 mg/dL |
| Pioglitazone | Change From Baseline in FPG at Week 32 | -44.0 mg/dL |
p-value: <0.00195% CI: [-19, -4.9]ANCOVA
Secondary
Percent of Participants With A1C <7.0% at Week 32
Time frame: Week 32
Population: The Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome. For FAS patients with no data at Week 32, the last non-baseline observed measurement was carried forward to Week 32.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin Fixed-Dose Combination | Percent of Participants With A1C <7.0% at Week 32 | 57.3 Percent Participants |
| Pioglitazone | Percent of Participants With A1C <7.0% at Week 32 | 43.5 Percent Participants |
p-value: <0.00195% CI: [1.3, 2.8]Regression, Logistic