Type 2 Diabetes
Conditions
Brief summary
A study to assess the safety and efficacy of sitagliptin 100mg compared to sitagliptin 200mg in patients with type 2 diabetes.
Interventions
DRUGsitagliptin phosphate
sitagliptin 100 mg tablets q.d. (once daily) for 7 days.
DRUGComparator: Placebo
sitagliptin 100 mg & 200 mg matching Placebo tablets q.d. (once daily) for 7 days.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patient has Type 2 Diabetes * Patient is between the ages of 30-65 years * Patient is not on an antihyperglycemic agent (AHA) (glycosylated hemoglobin \[A1C\] 7-10% ), or is on oral single AHA or low-dose combination therapy (A1C 6.5-9.5%).
Exclusion criteria
* Patient has Type 1 Diabetes * Patient has been treated with sitagliptin, vildagliptin, or other similar drugs or has been treated with exenatide in the past 3 months * Patient has taken insulin within the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Weighted Mean Glucose (WMG) | Day 7 of Treatment Period I. Due to a carry-over effect that was observed between treatment periods, efficacy results are presented from Treatment Period I only. | The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC(0-24 hr)) divided by 24 using linear trapezoidal method. |
Participant flow
Recruitment details
First Patient In: 17-Oct-2007; Last Patient Last Visit: 01-Jul-2008; Seventeen medical clinics worldwide (8 in the United States, 8 in Europe and 1 in Mexico).
Pre-assignment details
Following a 4-week (wk) diet/exercise (and wash-off period for patients on antihyperglycemic agent \[AHA\]), patients with fasting plasma glucose (FPG) 130-250 mg/dL were eligible to enter a 2-wk placebo run-in period prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo / 100 mg / 200 mg Placebo / 100 mg / 200 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin-matching placebo in Treatment Period I, sitagliptin 100 mg in Treatment Period II (after Washout Period I), and sitagliptin 200 mg in Treatment Period III (after Washout Period II) | 17 |
| 100 mg / 200 mg / Placebo 100 mg / 200 mg / Placebo Group includes patients receiving once daily administration of the following treatments: sitagliptin 100 mg in Treatment Period I, sitagliptin 200 mg in Treatment Period II (after Washout Period I), and sitagliptin-matching placebo in Treatment Period III (after Washout Period II) | 16 |
| 200 mg / Placebo / 100 mg 200 mg / Placebo / 100 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin 200 mg in Treatment Period I, sitagliptin-matching placebo in Treatment Period II (after Washout Period I), and sitagliptin 100 mg in Treatment Period III (after Washout Period II) | 20 |
| Placebo / 200 mg / 100 mg Placebo / 200 mg / 100 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin-matching placebo in Treatment Period I, sitagliptin 200 mg in Treatment Period II (after Washout Period I), and sitagliptin 100 mg in Treatment Period III (after Washout Period II) | 18 |
| 100 mg / Placebo / 200 mg 100 mg / Placebo / 200 mg Group includes patients receiving once daily administration of the following treatments: sitagliptin 100 mg in Treatment Period I, sitagliptin-matching placebo in Treatment Period II (after Washout Period I), and sitagliptin 200 mg in Treatment Period III (after Washout Period II) | 14 |
| 200 mg / 100 mg / Placebo 200 mg / 100 mg / Placebo includes patients receiving once daily administration of the following treatments: sitagliptin 200 mg in Treatment Period I, sitagliptin 100 mg in Treatment Period II (after Washout Period I), and sitagliptin-matching placebo in Treatment Period III (after Washout Period II) | 18 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period III (Week 11) | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Treatment Period III (Week 11) | Protocol Specified Criteria | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Period III (Week 11) | Study Terminated by Sponsor | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period II (Week 6) | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 1 |
| Treatment Period II (Week 6) | Study Terminated by Sponsor | 2 | 1 | 1 | 1 | 1 | 2 |
| Treatment Period I (Week 1) | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period I (Week 1) | Protocol Specified Criteria | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Period I (Week 1) | Study Terminated by Sponsor | 0 | 1 | 2 | 1 | 0 | 0 |
| Treatment Period I (Week 1) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
| Washout Period II (Week 7-10) | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Washout Period II (Week 7-10) | Study Terminated by Sponsor | 3 | 4 | 2 | 4 | 3 | 3 |
| Washout Period II (Week 7-10) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
| Washout Period I (Week 2-5) | Adverse Event | 1 | 0 | 1 | 0 | 0 | 0 |
| Washout Period I (Week 2-5) | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 |
| Washout Period I (Week 2-5) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Washout Period I (Week 2-5) | Study Terminated by Sponsor | 3 | 2 | 3 | 3 | 1 | 4 |
Baseline characteristics
| Characteristic | Placebo / 100 mg / 200 mg | 100 mg / 200 mg / Placebo | 200 mg / Placebo / 100 mg | Placebo / 200 mg / 100 mg | 100 mg / Placebo / 200 mg | 200 mg / 100 mg / Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.5 years STANDARD_DEVIATION 8.4 | 56.6 years STANDARD_DEVIATION 5.8 | 55.7 years STANDARD_DEVIATION 7.2 | 55.3 years STANDARD_DEVIATION 8.3 | 50.0 years STANDARD_DEVIATION 10 | 48.6 years STANDARD_DEVIATION 9.6 | 53.5 years STANDARD_DEVIATION 8.6 |
| Fasting Plasma Glucose | 179.3 mg/dL STANDARD_DEVIATION 32.1 | 167.0 mg/dL STANDARD_DEVIATION 41.1 | 184.0 mg/dL STANDARD_DEVIATION 42.1 | 173.2 mg/dL STANDARD_DEVIATION 43.2 | 158.5 mg/dL STANDARD_DEVIATION 17.3 | 166.0 mg/dL STANDARD_DEVIATION 36.5 | 172.0 mg/dL STANDARD_DEVIATION 36.9 |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other | 5 participants | 2 participants | 5 participants | 3 participants | 3 participants | 5 participants | 23 participants |
| Race/Ethnicity, Customized White | 12 participants | 14 participants | 15 participants | 15 participants | 11 participants | 12 participants | 79 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 7 Participants | 4 Participants | 4 Participants | 3 Participants | 28 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 13 Participants | 14 Participants | 10 Participants | 15 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 78 | 2 / 72 | 4 / 74 |
| serious Total, serious adverse events | 0 / 78 | 0 / 72 | 0 / 74 |
Outcome results
Primary
24-hour Weighted Mean Glucose (WMG)
The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC(0-24 hr)) divided by 24 using linear trapezoidal method.
Time frame: Day 7 of Treatment Period I. Due to a carry-over effect that was observed between treatment periods, efficacy results are presented from Treatment Period I only.
Population: The per-protocol (PP) population consisted of all patients randomized who had a measurement at Day 7 in Treatment Period I and did not have any major protocol violations. Missing data were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 200mg | 24-hour Weighted Mean Glucose (WMG) | 169.1 mg/dL |
| Sitagliptin 100mg | 24-hour Weighted Mean Glucose (WMG) | 159.0 mg/dL |
| Placebo | 24-hour Weighted Mean Glucose (WMG) | 200.9 mg/dL |
Comparison: For this comparison, the mean in the placebo group was subtracted from the mean in the sitagliptin 200 mg group.p-value: 0.00495% CI: [-53.1, -10.5]ANOVA
Comparison: For this comparison, the mean in the placebo group was subtracted from the mean in the sitagliptin 100 mg group.p-value: <0.00195% CI: [-63.6, -20.2]ANOVA
Comparison: This was pre-defined as a non-superiority test, i.e., to show that sitagliptin 200 mg is not superior to sitagliptin 100 mg. For this comparison, the mean in the sitagliptin 100 mg group was subtracted from the mean in the sitagliptin 200 mg group.80% CI: [0.61, 9999999]