Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of sitagliptin and MK0431A in comparison to a commonly used medication in patients with type 2 diabetes.
Interventions
DRUGComparator: sitagliptin phosphate (sitagliptin)
sitagliptin 100 mg tablet q.d. orally for a 12-wk treatment period
sitagliptin/metformin HCl (Sita/Met) 50/500 mg b.i.d. orally and then 50/1000 mg b.i.d. orally for a 28-wk treatment period
pioglitazone 15 mg tablet q.d. orally for 6 weeks, followed by 30 mg q.d orally for 6 weeks, followed by 45 mg q.d. orally, up to 40 weeks.
matching placebo to pioglitazone tablet q.d. orally, for a 40-wk treatment period. Participants were administered matching placebo the 15 mg pioglitazone q.d. orally for 6 weeks, followed by matching placebo to 30 mg pioglitazone q.d orally for 6 weeks, followed by matching placebo to 45 mg pioglitazone q.d. orally, up to 40 weeks.
matching placebo to sitagliptin q.d., orally for a 12-wk treatment period.
DRUGMatching Placebo to Sita/Met FDC
matching placebo to Sita/Met FDC - 50/500 mg b.i.d. for 4 weeks and then 50/1000 mg b.i.d. orally for a 28-wk treatment period (Week 12 to Week 40).
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
* Patients between the ages of 18 and 78 with type 2 diabetes mellitus * Patient has not been on any antihyperglycemic agent (Insulin or oral) in the last 3 months
Exclusion criteria
* Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis * Patient has previously been treated with sitagliptin or has previously been in a study using a DPP-4 inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin A1c (A1C) in the Sita/Met Fixed-Dose Combination (FDC) or Pioglitazone Groups at 40 Weeks | Baseline to 40 weeks | The change in A1C, compared to baseline for the Sita/Met FDC and the pioglitazone groups at Week 40. A1C represents percentage of glycosylated hemoglobin. |
| Change in Hemoglobin A1c (A1C) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | Baseline to 12 weeks | The change in A1C compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. A1c represents percentage of glycosylated hemoglobin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 2-hour Postprandial Glucose (PMG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks | Baseline and 40 weeks | The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the Sita/Met FDC and the pioglitazone groups at Week 40. |
| Change in 2-hour Postprandial Glucose (PMG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | Baseline to 12 weeks | The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the participants treated with Sitagliptin or Pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate. |
| Change in Fasting Plasma Glucose (FPG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks | Baseline and 40 weeks | The change in FPG compared to baseline was measured for the Sita/Met FDC and the pioglitazone groups at Week 40. |
| Change in Fasting Plasma Glucose (FPG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | Baseline to 12 weeks | The change in FPG compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sita/Met FDC In Phase A (Treatment Day 1 up to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to pioglitazone.
In Phase B (Treatment Week 12 to Week 40), participants that continued were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks. | 244 |
| Pioglitazone In Phase A (Treatment Day 1 up to Week 12), participants in the pioglitazone group were administered 15 mg once daily (q.d.) of pioglitazone and matching placebo to sitagliptin. At Week 6, all participants were administered 30 mg q.d. pioglitazone.
In Phase B (Treatment Week 12 to Week 40), participants that continued were administered 45 mg pioglitazone once daily (q.d.). | 248 |
| Total | 492 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase A | Adverse Event | 3 | 0 |
| Phase A | Creatinine/CrCl -Increase in creatinine | 0 | 2 |
| Phase A | Hyperglycemia | 0 | 1 |
| Phase A | Lost to Follow-up | 6 | 4 |
| Phase A | Physician Decision | 2 | 0 |
| Phase A | Protocol Violation | 2 | 3 |
| Phase A | Withdrawal by Subject | 7 | 7 |
| Phase B | Adverse Event | 6 | 6 |
| Phase B | Hyperglycemia | 10 | 9 |
| Phase B | Lost to Follow-up | 6 | 4 |
| Phase B | Physician Decision | 4 | 2 |
| Phase B | Pregnancy | 0 | 1 |
| Phase B | Protocol Violation | 3 | 3 |
| Phase B | Withdrawal by Subject | 8 | 6 |
Baseline characteristics
| Characteristic | Sita/Met FDC | Pioglitazone | Total |
|---|---|---|---|
| Age, Continuous | 50.5 years STANDARD_DEVIATION 10.9 | 51.7 years STANDARD_DEVIATION 10.1 | 51.1 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 92 Participants | 100 Participants | 192 Participants |
| Sex: Female, Male Male | 152 Participants | 148 Participants | 300 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 244 | 15 / 248 | 20 / 222 | 33 / 230 |
| serious Total, serious adverse events | 3 / 244 | 1 / 248 | 8 / 222 | 3 / 230 |
Outcome results
Primary
Change in Hemoglobin A1c (A1C) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks
The change in A1C compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. A1c represents percentage of glycosylated hemoglobin.
Time frame: Baseline to 12 weeks
Population: All randomized participants who (1) took at least one dose of study medication; i.e., sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12; and (2) had a baseline measurement and at least one on-treatment measurement for A1C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sita/Met FDC | Change in Hemoglobin A1c (A1C) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | -1.03 percentage of glycosylated hemoglobin |
| Pioglitazone | Change in Hemoglobin A1c (A1C) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | -0.87 percentage of glycosylated hemoglobin |
95% CI: [-0.37, 0.05]ANCOVA
Primary
Change in Hemoglobin A1c (A1C) in the Sita/Met Fixed-Dose Combination (FDC) or Pioglitazone Groups at 40 Weeks
The change in A1C, compared to baseline for the Sita/Met FDC and the pioglitazone groups at Week 40. A1C represents percentage of glycosylated hemoglobin.
Time frame: Baseline to 40 weeks
Population: All randomized participants who (1) took at least one dose of study medication; i.e., sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12, and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 (Phase A and Phase B); and~(2) had a baseline measurement and at least one on-treatment measurement for A1C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sita/Met FDC | Change in Hemoglobin A1c (A1C) in the Sita/Met Fixed-Dose Combination (FDC) or Pioglitazone Groups at 40 Weeks | -1.75 percentage of glycosylated hemoglobin |
| Pioglitazone | Change in Hemoglobin A1c (A1C) in the Sita/Met Fixed-Dose Combination (FDC) or Pioglitazone Groups at 40 Weeks | -1.38 percentage of glycosylated hemoglobin |
p-value: 0.002ANCOVA
Secondary
Change in 2-hour Postprandial Glucose (PMG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks
The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the participants treated with Sitagliptin or Pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate.
Time frame: Baseline to 12 weeks
Population: All randomized participants who (1) took at least one dose of study medication; i.e., sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12; and (2) had a baseline measurement and at least one on-treatment measurement for PMG.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sita/Met FDC | Change in 2-hour Postprandial Glucose (PMG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | -52.8 mg/dL |
| Pioglitazone | Change in 2-hour Postprandial Glucose (PMG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | -50.1 mg/dL |
Secondary
Change in 2-hour Postprandial Glucose (PMG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks
The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the Sita/Met FDC and the pioglitazone groups at Week 40.
Time frame: Baseline and 40 weeks
Population: All randomized participants who (1) took at least one dose of study medication; i.e., sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12, and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 (Phase A and Phase B); and~(2) had a baseline measurement and at least one on-treatment measurement for PMG.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sita/Met FDC | Change in 2-hour Postprandial Glucose (PMG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks | -90.3 mg/dL |
| Pioglitazone | Change in 2-hour Postprandial Glucose (PMG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks | -69.1 mg/dL |
p-value: 0.001ANCOVA
Secondary
Change in Fasting Plasma Glucose (FPG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks
The change in FPG compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate.
Time frame: Baseline to 12 weeks
Population: All randomized participants who (1) took at least one dose of study medication; i.e., sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12; and (2) had a baseline measurement and at least one on-treatment measurement for FPG.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sita/Met FDC | Change in Fasting Plasma Glucose (FPG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | -26.6 mg/dL |
| Pioglitazone | Change in Fasting Plasma Glucose (FPG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | -28.0 mg/dL |
Secondary
Change in Fasting Plasma Glucose (FPG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks
The change in FPG compared to baseline was measured for the Sita/Met FDC and the pioglitazone groups at Week 40.
Time frame: Baseline and 40 weeks
Population: All randomized participants who (1) took at least one dose of study medication; i.e., sitagliptin or pioglitazone 15/30 mg q.d. for the Weeks 0-12, and Sita/Met FDC or pioglitazone 45 mg q.d. for the Weeks 0-40 (Phase A and Phase B); and (2) had a baseline measurement and at least one on-treatment measurement for FPG.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sita/Met FDC | Change in Fasting Plasma Glucose (FPG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks | -45.8 mg/dL |
| Pioglitazone | Change in Fasting Plasma Glucose (FPG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks | -37.6 mg/dL |
p-value: 0.03ANCOVA