Diabetes
Conditions
Brief summary
The purpose of this trial is to understand if adding saxagliptin to a sulfonylurea is safe and works better than increasing the amount of sulfonylurea a patient takes
Detailed description
All subjects will participate in a lead-in period, and qualifying subjects will continue into a short-term randomized treatment period. Subjects who complete the short-term period will be eligible to enter the long term extension period. Also, subjects in the short-term period who have an elevated blood sugar that requires additional medication for blood sugar control (defined as rescue) will be eligible to enter the long-term treatment extension period where they will receive metformin.Rescue treatment with metformin is also available during the long-term extension period for subjects who meet glycemic criteria.
Interventions
DRUGSaxagliptin
Tablets, Oral, 2.5 mg, Daily AM, (24 weeks short-term \[ST\], 12 months long-term \[LT\])
DRUGGlyburide
Capsules, Oral, OL, 7.5 mg, Daily, AM (24 weeks ST, 12 months LT)
DRUGPlacebo
Tablets, Oral, 0 mg, Daily AM/PM, (24 weeks ST, 12 months LT)
DRUGMetformin
Tablets, Oral, OL, 500 - 2500 mg, 1 or 2 times per day (12 months LT)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 77 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 Diabetes. * Treated with a sulfonylurea for at least 2 months. * Inadequate blood sugar control. * Are not on any other medications to lower blood sugar. * No major heart, liver or kidney problems. * Women not pregnant or breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Baseline, Week 24 | Mean change from baseline in A1C at Week 24, adjusted for baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline, Week 24 | Mean change from baseline in FPG at Week 24, adjusted for baseline value. |
| Percentage of Participants Achieving A1C < 7% at Week 24 | Week 24 | Percentage of participants achieving A1C \< 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus glyburide versus placebo plus upward titrated glyburide at Week 24. |
| Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Baseline, Week 24 | Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline values. |
Countries
Argentina, Brazil, Hong Kong, Israel, Mexico, Peru, Philippines, Puerto Rico, Singapore, South Africa, South Korea, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Saxagliptin 2.5 mg + Glyburide 7.5 mg The Saxagliptin 2.5 mg + Glyburide 7.5 mg group includes data from subjects randomized to receive coadministration of blinded saxagliptin 2.5 mg oral tablets and open-label glyburide 7.5 mg oral tables once daily. Open-label glyburide may have been down titrated by 2.5 mg once due to hypoglycemia as deemed necessary by the investigator. | 248 |
| Saxagliptin 5 mg + Glyburide 7.5 mg The Saxagliptin 5 mg + Glyburide 7.5 mg group includes data from subjects randomized to receive coadministration of blinded saxagliptin 5 mg oral tablets and open-label glyburide 7.5 mg oral tables once daily. Open-label glyburide may have been down titrated by 2.5 mg once due to hypoglycemia as deemed necessary by the investigator. | 253 |
| Placebo + Glyburide 7.5 mg The Placebo + Glyburide 7.5 mg group includes data from subjects randomized to receive coadministration of blinded placebo oral tablets, blinded glyburide 2.5 mg, and open-label glyburide 7.5 mg once daily. Open-label glyburide may have been down titrated by 2.5 mg once due to hypoglycemia as deemed necessary by the investigator. Blinded glyburide may have been uptitrated by 5 mg according to glycemic criteria provided it had not been previously down-titrated. | 267 |
| Total | 768 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 15 | 16 | 12 |
| Overall Study | Death | 0 | 0 | 2 |
| Overall Study | Lack of Efficacy | 14 | 9 | 20 |
| Overall Study | Lost to Follow-up | 10 | 7 | 9 |
| Overall Study | Physician Decision | 2 | 6 | 4 |
| Overall Study | Poor/Noncompliance | 3 | 6 | 2 |
| Overall Study | Pregnancy | 1 | 2 | 0 |
| Overall Study | Subject No Longer Meets Study Criteria | 0 | 3 | 2 |
| Overall Study | Withdrawal of consent by subject | 18 | 17 | 31 |
Baseline characteristics
| Characteristic | Saxagliptin 2.5 mg + Glyburide 7.5 mg | Saxagliptin 5 mg + Glyburide 7.5 mg | Placebo + Glyburide 7.5 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 55.36 years STANDARD_DEVIATION 9.58 | 54.85 years STANDARD_DEVIATION 9.96 | 55.06 years STANDARD_DEVIATION 10.69 | 55.09 years STANDARD_DEVIATION 10.09 |
| Sex: Female, Male Female | 135 Participants | 143 Participants | 144 Participants | 422 Participants |
| Sex: Female, Male Male | 113 Participants | 110 Participants | 123 Participants | 346 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 | 163 / 267 | 144 / 248 | 154 / 253 |
| serious Total, serious adverse events | 23 / 267 | 18 / 248 | 12 / 253 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (A1C) at Week 24
Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Time frame: Baseline, Week 24
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 Last Observation Carried Forward (LOCF), participants must have had a baseline and at least 1 post-baseline measurement. If participant received rescue medication, measurement must have been taken before rescue.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Week 24 Mean | 7.83 percent | Standard Error 0.074 |
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Baseline Mean | 8.36 percent | Standard Error 0.057 |
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Adjusted Mean Change from Baseline | -0.54 percent | Standard Error 0.059 |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Week 24 Mean | 7.83 percent | Standard Error 0.074 |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Baseline Mean | 8.48 percent | Standard Error 0.056 |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Adjusted Mean Change from Baseline | -0.64 percent | Standard Error 0.059 |
| Placebo + Glyburide 7.5 mg | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Baseline Mean | 8.44 percent | Standard Error 0.055 |
| Placebo + Glyburide 7.5 mg | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Adjusted Mean Change from Baseline | 0.08 percent | Standard Error 0.057 |
| Placebo + Glyburide 7.5 mg | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Week 24 Mean | 8.52 percent | Standard Error 0.077 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Mean change from baseline in FPG at Week 24, adjusted for baseline value.
Time frame: Baseline, Week 24
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Adjusted Mean Change from Baseline | -7.1 mg/dL | Standard Error 2.42 |
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 Mean | 164.4 mg/dL | Standard Error 2.76 |
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline Mean | 170.1 mg/dL | Standard Error 2.67 |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Adjusted Mean Change from Baseline | -9.7 mg/dL | Standard Error 2.39 |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline Mean | 175.0 mg/dL | Standard Error 2.79 |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 Mean | 164.6 mg/dL | Standard Error 2.76 |
| Placebo + Glyburide 7.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 Mean | 174.6 mg/dL | Standard Error 2.93 |
| Placebo + Glyburide 7.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline Mean | 174.4 mg/dL | Standard Error 2.64 |
| Placebo + Glyburide 7.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Adjusted Mean Change from Baseline | 0.7 mg/dL | Standard Error 2.33 |
Secondary
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24
Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline values.
Time frame: Baseline, Week 24
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Week 24 Mean | 45402 mg*min/dL | Standard Error 681.5 |
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Baseline Mean | 49124 mg*min/dL | Standard Error 677.2 |
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Adjusted Mean Change from Baseline | -4296 mg*min/dL | Standard Error 595 |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Week 24 Mean | 45391 mg*min/dL | Standard Error 699.3 |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Baseline Mean | 50342 mg*min/dL | Standard Error 669 |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Adjusted Mean Change from Baseline | -5000 mg*min/dL | Standard Error 585.5 |
| Placebo + Glyburide 7.5 mg | Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Baseline Mean | 51801 mg*min/dL | Standard Error 656.9 |
| Placebo + Glyburide 7.5 mg | Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Adjusted Mean Change from Baseline | 1196 mg*min/dL | Standard Error 574.5 |
| Placebo + Glyburide 7.5 mg | Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 | Week 24 Mean | 52416 mg*min/dL | Standard Error 703.7 |
Secondary
Percentage of Participants Achieving A1C < 7% at Week 24
Percentage of participants achieving A1C \< 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus glyburide versus placebo plus upward titrated glyburide at Week 24.
Time frame: Week 24
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, participants must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin 2.5 mg + Glyburide 7.5 mg | Percentage of Participants Achieving A1C < 7% at Week 24 | 22.4 Percentage of participants |
| Saxagliptin 5 mg + Glyburide 7.5 mg | Percentage of Participants Achieving A1C < 7% at Week 24 | 22.8 Percentage of participants |
| Placebo + Glyburide 7.5 mg | Percentage of Participants Achieving A1C < 7% at Week 24 | 9.1 Percentage of participants |