Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes Mellitus
Brief summary
A clinical study to determine the safety and efficacy of sitagliptin in patients with Type 2 Diabetes Mellitus who have inadequate glycemic control on metformin/peroxisome proliferator-activated receptor gamma (PPARg) agonist combination therapy.
Interventions
DRUGsitagliptin
Sitagliptin 100mg tablet each day for 54 weeks. All subjects will be given placebo to sitagliptin for a 2 week period.
DRUGComparator: Placebo
Placebo to sitagliptin 100mg tablet each day for 54 weeks.
DRUGrosiglitazone
Subjects taking 4mg or greater rosiglitazone at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 4mg/day or no rosiglitazone at screening will be titrated to a stable dose of at least 4mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.
DRUGmetformin
Subjects taking 1500mg or greater metformin at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 1500mg/day or no metformin at screening will be titrated to a stable dose of at least 1500mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.
DRUGglipizide
Subjects not meeting specific glycemic controls during the 54-week treatment period will use glipizide as rescue therapy. Glipizide will be titrated in 5mg doses up to a maximum 40mg each day. (In Canada, the rescue therapy will be a sulfonylurea agent marketed in that country.)
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 * Patient is inadequately controlled while taking 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 3 months * Patient has been taking Byetta (R) (exenatide) within the prior 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18 | Baseline and 18 Weeks | HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18 | Baseline and 18 Weeks | Change from baseline at Week 18 is defined as Week 18 minus Week 0 |
| Change From Baseline in 2-hour PMG (Post-meal Glucose) 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 HbA1c (Hemoglobin A1C) at Week 54 | Baseline and Week 54 | HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent. |
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | Baseline and Week 54 | Change from baseline at Week 54 is defined as Week 54 minus Week 0 |
| Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54 | Baseline and Week 54 | Change from baseline at Week 54 is defined as Week 54 minus Week 0. |
Participant flow
Recruitment details
Phase III First Patient In: 29-Aug-06. Last Patient Enrolled: 23-Mar-07. Last Patient Last Visit: 27-May-08; 41 study centers worldwide
Pre-assignment details
Patients 18-78 years of age with T2DM and inadequate glycemic control (HbA1c ≥7.5 and ≤11.0%) who were on stable doses of rosiglitazone (≥4 mg/day) and metformin (≥1500 mg/day) after an up to 20-week dose-titration and stabilization period were eligible to enter the 54-week study.
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 (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day). | 170 |
| Placebo The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label rosiglitazone 4 mg oral tablets (4 to 8 mg/day) and open-label metformin 500 mg oral tablets (≥1500 mg/day). | 92 |
| Total | 262 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Lack of Efficacy | 0 | 4 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Non-compliance with study procedures | 0 | 1 |
| Overall Study | Patient Moved | 2 | 1 |
| Overall Study | Physician Decision | 2 | 4 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 8 |
Baseline characteristics
| Characteristic | Sitagliptin 100 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 8.8 | 54.8 years STANDARD_DEVIATION 9.5 | 54.5 years STANDARD_DEVIATION 9 |
| HbA1c (Hemoglobin A1c) | 8.8 Percent STANDARD_DEVIATION 1 | 8.7 Percent STANDARD_DEVIATION 1 | 8.8 Percent STANDARD_DEVIATION 1 |
| Race/Ethnicity Asian | 58 participants | 24 participants | 82 participants |
| Race/Ethnicity Black | 7 participants | 3 participants | 10 participants |
| Race/Ethnicity Hispanic | 13 participants | 10 participants | 23 participants |
| Race/Ethnicity Other | 10 participants | 4 participants | 14 participants |
| Race/Ethnicity White | 82 participants | 51 participants | 133 participants |
| Sex: Female, Male Female | 74 Participants | 37 Participants | 111 Participants |
| Sex: Female, Male Male | 96 Participants | 55 Participants | 151 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 | 20 / — | 14 / — | 70 / — | 35 / — |
| serious Total, serious adverse events | 2 / — | 2 / — | 14 / — | 4 / — |
Outcome results
Primary
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.
Time frame: Baseline and 18 Weeks
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 18, the last non-baseline observed measurement was carried forward to Week 18.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18 | -1.03 Percent |
| Placebo | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18 | -0.31 Percent |
p-value: <0.00195% CI: [-0.95, -0.49]ANCOVA
Secondary
Change From Baseline in 2-hour PMG (Post-meal Glucose) 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) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 18, the last non-baseline observed measurement was carried forward to Week 18.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18 | -59.9 mg/dL |
| Placebo | Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18 | -22.0 mg/dL |
p-value: <0.00195% CI: [-50.2, -25.5]ANCOVA
Secondary
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54
Change from baseline at Week 54 is defined as Week 54 minus Week 0.
Time frame: Baseline and Week 54
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 54, the last non-baseline observed measurement was carried forward to Week 54.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54 | -50.7 mg/dL |
| Placebo | Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54 | -16.6 mg/dL |
p-value: <0.00195% CI: [-48.4, -19.9]ANCOVA
Secondary
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18
Change from baseline at Week 18 is defined as Week 18 minus Week 0
Time frame: Baseline and 18 Weeks
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 18, the last non-baseline observed measurement was carried forward to Week 18.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18 | -30.7 mg/dL |
| Placebo | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18 | -11.7 mg/dL |
p-value: <0.00195% CI: [-27.2, -10.9]ANCOVA
Secondary
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54
Change from baseline at Week 54 is defined as Week 54 minus Week 0
Time frame: Baseline and Week 54
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 54, the last non-baseline observed measurement was carried forward to Week 54.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | -28.0 mg/dL |
| Placebo | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | -10.7 mg/dL |
p-value: <0.00195% CI: [-26.4, -8.4]ANCOVA
Secondary
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.
Time frame: Baseline and Week 54
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 54, the last non-baseline observed measurement was carried forward to Week 54.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | -1.05 Percent |
| Placebo | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | -0.28 Percent |
p-value: <0.00195% CI: [-1.04, -0.5]ANCOVA