Diabetes
Conditions
Brief summary
The purpose of this trial is to understand if saxagliptin is more effective than placebo as a treatment for type 2 diabetic subjects who are not controlled with diet and exercise
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 will be eligible to enter the long-term treatment extension period where they will receive metformin (rescue medication) added onto their blinded study medication
Interventions
DRUGSaxagliptin
Coated tablets, Oral, 2.5 mg, QAM, Daily (6 months ST, 12 months LT)
DRUGPlacebo
Coated tablets, Oral, 0mg, Daily (6 months ST, 12 months LT)
DRUGmetformin
Tablets, Oral, 500-2000 mg, as needed (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 * Inadequate blood sugar control
Exclusion criteria
* Previous treatment for diabetes * Current treatment with other medications to lower blood sugar * Major heart, liver or kidney problems * Women who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1 (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 A1C at Week 24 - Saxagliptin 5 mg QPM | Baseline, Week 24 | Mean change from baseline in A1C at Week 24, adjusted for baseline value. |
| 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 versus placebo 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 value. |
Countries
India, Russia, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Saxagliptin 2.5 mg Once in the Morning (QAM) The Saxagliptin 2.5 mg QAM group includes data from subjects randomized to receive administration of blinded Saxagliptin 2.5 mg oral tablets QAM daily. | 74 |
| Saxagliptin 5 mg QAM The Saxagliptin 5 mg QAM group includes data from subjects randomized to receive administration of blinded Saxagliptin 5 mg oral tablets QAM daily. | 74 |
| Saxagliptin 2.5/5 mg QAM The Saxagliptin 2.5/5 mg QAM group includes data from subjects randomized to receive administration of blinded Saxagliptin 2.5 mg oral tablets QAM daily, with possible titration to 5 mg oral tablets QAM. | 71 |
| Saxagliptin 5 mg Once in the Evening (QPM) The Saxagliptin 5 mg QPM group includes data from subjects randomized to receive administration of blinded Saxagliptin 5 mg oral tablets QPM daily. | 72 |
| Placebo The Placebo group includes data from subjects randomized to receive administration of placebo oral tablets daily. | 74 |
| Total | 365 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Adverse Event | 4 | 2 | 5 | 1 | 3 |
| Overall Study | Death | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 2 | 3 | 3 | 4 | 6 |
| Overall Study | Lost to Follow-up | 7 | 6 | 7 | 8 | 6 |
| Overall Study | Physician Decision | 1 | 1 | 2 | 1 | 1 |
| Overall Study | Poor/noncompliance | 6 | 1 | 4 | 1 | 4 |
| Overall Study | Subject no longer meets study criteria | 3 | 1 | 2 | 2 | 1 |
| Overall Study | Withdrawal of Consent by Subject | 10 | 8 | 2 | 9 | 5 |
Baseline characteristics
| Characteristic | Saxagliptin 2.5 mg Once in the Morning (QAM) | Saxagliptin 5 mg QAM | Saxagliptin 2.5/5 mg QAM | Saxagliptin 5 mg Once in the Evening (QPM) | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 55.24 years STANDARD_DEVIATION 10.44 | 54.66 years STANDARD_DEVIATION 9.71 | 54.28 years STANDARD_DEVIATION 10.93 | 55.11 years STANDARD_DEVIATION 10.35 | 55.57 years STANDARD_DEVIATION 10.32 | 54.98 years STANDARD_DEVIATION 10.31 |
| Sex: Female, Male Female | 49 Participants | 36 Participants | 34 Participants | 39 Participants | 39 Participants | 197 Participants |
| Sex: Female, Male Male | 25 Participants | 38 Participants | 37 Participants | 33 Participants | 35 Participants | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 74 | 30 / 71 | 32 / 74 | 33 / 74 | 29 / 72 |
| serious Total, serious adverse events | 5 / 74 | 7 / 71 | 7 / 74 | 8 / 74 | 4 / 72 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1 (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 QAM | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Baseline Mean | 8.04 percent | Standard Error 0.105 |
| Saxagliptin 2.5 mg QAM | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Adjusted Mean Change from Baseline | -0.71 percent | Standard Error 0.103 |
| Saxagliptin 2.5 mg QAM | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Week 24 Mean | 7.30 percent | Standard Error 0.106 |
| Saxagliptin 5 mg QAM | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Baseline Mean | 7.93 percent | Standard Error 0.106 |
| Saxagliptin 5 mg QAM | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Adjusted Mean Change from Baseline | -0.66 percent | Standard Error 0.102 |
| Saxagliptin 5 mg QAM | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Week 24 Mean | 7.27 percent | Standard Error 0.129 |
| Saxagliptin 2.5/5 mg QAM | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Week 24 Mean | 7.37 percent | Standard Error 0.137 |
| Saxagliptin 2.5/5 mg QAM | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Baseline Mean | 8.02 percent | Standard Error 0.131 |
| Saxagliptin 2.5/5 mg QAM | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Adjusted Mean Change from Baseline | -0.63 percent | Standard Error 0.102 |
| Placebo | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Baseline Mean | 7.79 percent | Standard Error 0.112 |
| Placebo | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Adjusted Mean Change from Baseline | -0.26 percent | Standard Error 0.103 |
| Placebo | Change From Baseline in Hemoglobin A1 (A1C) at Week 24 | Week 24 Mean | 7.57 percent | Standard Error 0.141 |
Secondary
Change From Baseline in A1C at Week 24 - Saxagliptin 5 mg QPM
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 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 QAM | Change From Baseline in A1C at Week 24 - Saxagliptin 5 mg QPM | Baseline Mean | 7.88 percent | Standard Error 0.111 |
| Saxagliptin 2.5 mg QAM | Change From Baseline in A1C at Week 24 - Saxagliptin 5 mg QPM | Week 24 Mean | 7.29 percent | Standard Error 0.124 |
| Saxagliptin 2.5 mg QAM | Change From Baseline in A1C at Week 24 - Saxagliptin 5 mg QPM | Adjusted Mean Change from Baseline | -0.61 percent | Standard Error 0.101 |
| Saxagliptin 5 mg QAM | Change From Baseline in A1C at Week 24 - Saxagliptin 5 mg QPM | Baseline Mean | 7.79 percent | Standard Error 0.112 |
| Saxagliptin 5 mg QAM | Change From Baseline in A1C at Week 24 - Saxagliptin 5 mg QPM | Week 24 Mean | 7.57 percent | Standard Error 0.141 |
| Saxagliptin 5 mg QAM | Change From Baseline in A1C at Week 24 - Saxagliptin 5 mg QPM | Adjusted Mean Change from Baseline | -0.26 percent | Standard Error 0.103 |
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 QAM | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline Mean | 156.6 mg/dL | Standard Error 3.96 |
| Saxagliptin 2.5 mg QAM | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Adjusted Mean Change from Baseline | -11.4 mg/dL | Standard Error 4.5 |
| Saxagliptin 2.5 mg QAM | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 Mean | 146.8 mg/dL | Standard Error 3.79 |
| Saxagliptin 5 mg QAM | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 Mean | 151.3 mg/dL | Standard Error 5.88 |
| Saxagliptin 5 mg QAM | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline Mean | 162.2 mg/dL | Standard Error 4.24 |
| Saxagliptin 5 mg QAM | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Adjusted Mean Change from Baseline | -10.7 mg/dL | Standard Error 4.46 |
| Saxagliptin 2.5/5 mg QAM | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 Mean | 155.2 mg/dL | Standard Error 5.88 |
| Saxagliptin 2.5/5 mg QAM | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline Mean | 170.6 mg/dL | Standard Error 6.15 |
| Saxagliptin 2.5/5 mg QAM | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Adjusted Mean Change from Baseline | -12.5 mg/dL | Standard Error 4.48 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline Mean | 159.6 mg/dL | Standard Error 5.32 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Adjusted Mean Change from Baseline | -7.9 mg/dL | Standard Error 4.46 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 Mean | 152.4 mg/dL | Standard Error 5.88 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 Mean | 162.9 mg/dL | Standard Error 6.28 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline Mean | 158.6 mg/dL | Standard Error 5.44 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Adjusted Mean Change from Baseline | 3.3 mg/dL | Standard Error 4.46 |
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 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 QAM | 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 | 47432 mg*min/dL | Standard Error 1496.6 |
| Saxagliptin 2.5 mg QAM | 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 | -8014 mg*min/dL | Standard Error 1246.9 |
| Saxagliptin 2.5 mg QAM | 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 | 39798 mg*min/dL | Standard Error 1347 |
| Saxagliptin 5 mg QAM | 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 | 41562 mg*min/dL | Standard Error 1489.3 |
| Saxagliptin 5 mg QAM | 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 | 50417 mg*min/dL | Standard Error 1561.5 |
| Saxagliptin 5 mg QAM | 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 | -8218 mg*min/dL | Standard Error 1249.1 |
| Saxagliptin 2.5/5 mg QAM | 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 | 41745 mg*min/dL | Standard Error 1739.2 |
| Saxagliptin 2.5/5 mg QAM | 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 | 50032 mg*min/dL | Standard Error 1684.7 |
| Saxagliptin 2.5/5 mg QAM | 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 | -7781 mg*min/dL | Standard Error 1261 |
| Placebo | 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 | 47078 mg*min/dL | Standard Error 1941.9 |
| Placebo | 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 | -6048 mg*min/dL | Standard Error 1318.2 |
| Placebo | 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 | 41530 mg*min/dL | Standard Error 1962.7 |
| Placebo | 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 | 44861 mg*min/dL | Standard Error 1854.7 |
| Placebo | 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 | 47640 mg*min/dL | Standard Error 1759.7 |
| Placebo | 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 | -3088 mg*min/dL | Standard Error 1259.7 |
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 versus placebo 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 QAM | Percentage of Participants Achieving A1C < 7% at Week 24 | 35.8 Percentage of participants |
| Saxagliptin 5 mg QAM | Percentage of Participants Achieving A1C < 7% at Week 24 | 44.9 Percentage of participants |
| Saxagliptin 2.5/5 mg QAM | Percentage of Participants Achieving A1C < 7% at Week 24 | 43.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving A1C < 7% at Week 24 | 38.6 Percentage of participants |
| Placebo | Percentage of Participants Achieving A1C < 7% at Week 24 | 35.3 Percentage of participants |