Type 2 Diabetes Mellitus (T2DM)
Conditions
Brief summary
A clinical study to determine the safety and efficacy of sitagliptin in patients with Type 2 Diabetes Mellitus who have inadequate glycemic (blood sugar) control on metformin therapy.
Interventions
DRUGsitagliptin 100 mg q.d./metformin ≥ 1500 mg/day
Patients will receive blinded sitagliptin 100 mg q.d. and open-label metformin ≥ 1500 mg/day for up to 30 weeks. Sitagliptin 100 mg q.d. and metformin ≥ 1500 mg/day will be administered as oral tablets.
DRUGcomparator: placebo to match sitagliptin 100 mg q.d./metformin ≥ 1500 mg/day
Patients will receive placebo to match sitagliptin 100 mg q.d. and open-label metformin ≥ 1500 mg/day for up to 30 weeks. Sitagliptin 100 mg q.d. and metformin ≥ 1500 mg/day will be administered as oral tablets.
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
* Patient has type 2 diabetes mellitus * Males * Females who are highly unlikely to become pregnant * Patients poorly controlled while taking one or two oral antidiabetic medications
Exclusion criteria
* Patient has a history of type 1 diabetes mellitus or history of ketoacidosis * Patient required insulin therapy within the prior 8 weeks * Patient is on or has been taking Thiazolidinediones (TZDs) such as Actos® (pioglitazone) or Avandia® (rosiglitazone) or is on or has been taking Byetta® (exenatide) within the prior 12 weeks of the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in A1C at Week 18 | Baseline and Week 18 | A1C was measured as a percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FPG at Week 18 | Baseline and Week 18 | Change from baseline at Week 18 is defined as Week 18 FPG minus Week 0 FPG. |
| Change From Baseline in 2 Hr-PMG at Week 18 | Baseline and Week 18 | Change from baseline at Week 18 is defined as Week 18 minus Week 0. |
| Change From Baseline in A1C at Week 30 | Baseline and Week 30 | A1C was measured as a percent. Thus, this change from baseline reflects the Week 30 A1C percent minus the Week 0 A1C percent. |
Participant flow
Recruitment details
First Patient In: 21-Aug-2006; Last Patient Last Visit: 15-Aug-2007; Twenty-four medical clinics worldwide (12 in the United States, 2 in Israel, 3 in Mexico, 3 in Peru, and 4 in Austria).
Pre-assignment details
Patients 18-78 years on oral single antihyperglycemic agent (AHA) (hemoglobin A1C \[A1C\] ≥8%) or metformin-based dual combination therapy (A1C 7.5-10.5%) were eligible to participate. Eligible patients underwent an up to 12-week metformin dose-titration/dose-stable period followed by a 2-week placebo run-in period prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 100 mg The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day. | 96 |
| Placebo The Placebo group includes data from patients randomized to receive treatment with oral tablets of sitagliptin-matching placebo once daily in addition to ongoing treatment with open-label metformin ≥ 1500 mg/day. | 94 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 6 | 3 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Sitagliptin 100 mg | Total | Placebo |
|---|---|---|---|
| 2-Hour Post-Meal Glucose (2 hr PMG) | 288.7 mg/dL STANDARD_DEVIATION 74.8 | 287.7 mg/dL STANDARD_DEVIATION 68.5 | 286.7 mg/dL STANDARD_DEVIATION 61.7 |
| Age, Continuous | 53.6 years STANDARD_DEVIATION 9.5 | 54.8 years STANDARD_DEVIATION 9.5 | 56.1 years STANDARD_DEVIATION 9.5 |
| Fasting Plasma Glucose (FPG) | 201.1 mg/dL STANDARD_DEVIATION 46.2 | 199.7 mg/dL STANDARD_DEVIATION 45.3 | 198.2 mg/dL STANDARD_DEVIATION 44.6 |
| Hemoglobin A1C (A1C) | 9.3 Percent STANDARD_DEVIATION 0.9 | 9.2 Percent STANDARD_DEVIATION 0.8 | 9.1 Percent STANDARD_DEVIATION 0.8 |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black | 3 participants | 4 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 31 participants | 55 participants | 24 participants |
| Race/Ethnicity, Customized Other | 21 participants | 46 participants | 25 participants |
| Race/Ethnicity, Customized White | 40 participants | 84 participants | 44 participants |
| Sex: Female, Male Female | 47 Participants | 102 Participants | 55 Participants |
| Sex: Female, Male Male | 49 Participants | 88 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 96 | 29 / 94 |
| serious Total, serious adverse events | 0 / 96 | 5 / 94 |
Outcome results
Primary
Change From Baseline in A1C at Week 18
A1C was measured as a percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent.
Time frame: Baseline and Week 18
Population: The full-analysis-set (FAS) population included all patients with at least one dose of double-blind study therapy, and with a baseline value and ≥1 postbaseline value for this outcome. Data following glycemic rescue were treated as missing. Missing data were handled using the last observation carrying forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in A1C at Week 18 | -1.00 Percent |
| Placebo | Change From Baseline in A1C at Week 18 | 0.02 Percent |
p-value: <0.00195% CI: [-1.36, -0.67]ANCOVA
Secondary
Change From Baseline in 2 Hr-PMG at Week 18
Change from baseline at Week 18 is defined as Week 18 minus Week 0.
Time frame: Baseline and Week 18
Population: The full-analysis-set (FAS) population included all patients with at least one dose of double-blind study therapy, and with a baseline value and ≥1 postbaseline value for this outcome. Data following glycemic rescue were treated as missing. Missing data were handled using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in 2 Hr-PMG at Week 18 | -67.6 mg/dL |
| Placebo | Change From Baseline in 2 Hr-PMG at Week 18 | -13.5 mg/dL |
p-value: <0.00195% CI: [-74.7, -33.6]ANCOVA
Secondary
Change From Baseline in A1C at Week 30
A1C was measured as a percent. Thus, this change from baseline reflects the Week 30 A1C percent minus the Week 0 A1C percent.
Time frame: Baseline and Week 30
Population: The full-analysis-set (FAS) population included all patients with at least one dose of double-blind study therapy, and with a baseline value and ≥1 postbaseline value for this outcome. Data following glycemic rescue were treated as missing. Missing data were handled using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in A1C at Week 30 | -0.98 Percent |
| Placebo | Change From Baseline in A1C at Week 30 | 0.04 Percent |
p-value: <0.00195% CI: [-1.4, -0.62]ANCOVA
Secondary
Change From Baseline in FPG at Week 18
Change from baseline at Week 18 is defined as Week 18 FPG minus Week 0 FPG.
Time frame: Baseline and Week 18
Population: The full-analysis-set (FAS) population included all patients with at least one dose of double-blind study therapy, and with a baseline value and ≥1 postbaseline value for this outcome. Data following glycemic rescue were treated as missing. Missing data were handled using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in FPG at Week 18 | -32.0 mg/dL |
| Placebo | Change From Baseline in FPG at Week 18 | -6.5 mg/dL |
p-value: <0.00195% CI: [-37.7, -13.3]ANCOVA