Type 2 Diabetes
Conditions
Keywords
Type 2 diabetes, metformin
Brief summary
Saxagliptin is a new investigational medication being developed for treatment of type 2 diabetes. This study is designed to assess the efficacy and tolerability of saxagliptin in addition to metformin and compare to sitagliptin in addition with metformin.
Interventions
DRUGsaxagliptin
tablet, per oral, once daily
DRUGsitagliptin
capsule, per oral, once daily
Sponsors
Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 2 diabetes * Treatment with metformin alone on stable doses of 1500 mg or higher per day for at least 8 weeks
Exclusion criteria
* Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketotic coma * Insulin therapy within one year * Previous treatment with DPP-4 inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1c (HbA1c) Change From Baseline to Week 18 | Baseline, Week 18 | Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus sitagliptin added on to metformin at Week 18 (Per Protocol Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving Therapeutic Glycaemic Response Defined as HbA1c <= 6.5% at Week 18 | Week 18 (Last Observation Carried Forward) | Proportion of Patients Achieving Therapeutic Glycaemic Response Defined as HbA1c \<= 6.5% at Week 18 (Full Analysis Set) |
| Fasting Plasma Glucose Change From Baseline to Week 18 (mg/dL) | Baseline, Week 18 (Last Observation Carried Forward) | Adjusted mean change from baseline in Fasting Plasma Glucose achieved with saxagliptin added on to metformin versus sitagliptin added on to metformin at Week 18 (Full Analysis Set). Fasting Plasma Glucose is a continuous measure, the change from baseline for each participant is calculated as the Week 18 (LOCF) value minus the baseline value. |
| Fasting Plasma Glucose Change From Baseline to Week 18 (mmol/L) | Baseline, Week 18 (Last Observation Carried Forward) | Adjusted mean change from baseline in Fasting Plasma Glucose achieved with saxagliptin added on to metformin versus sitagliptin added on to metformin at Week 18 (Full Analysis Set). Fasting Plasma Glucose is a continuous measure, the change from baseline for each participant is calculated as the Week 18 (LOCF) value minus the baseline value. |
Countries
Argentina, Belgium, Denmark, France, Italy, Mexico, Norway, South Africa, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Saxa + Met Saxagliptin 5 mg tablets added on to open-label metformin | 403 |
| Sita + Met Sitagliptin 100 mg capsules added on to open-label metformin | 398 |
| Total | 801 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 1 | 1 |
| Overall Study | Adverse Event | 8 | 7 |
| Overall Study | Incorrect enrollment | 7 | 1 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Medical history of anemia | 1 | 0 |
| Overall Study | Safety reasons | 1 | 0 |
| Overall Study | Severe non-compliance to the protocol | 1 | 1 |
| Overall Study | Study specific discontinuation criteria | 14 | 7 |
| Overall Study | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | Saxa + Met | Sita + Met | Total |
|---|---|---|---|
| Age Continuous | 58.77 years STANDARD_DEVIATION 10.14 | 58.07 years STANDARD_DEVIATION 10.51 | 58.42 years STANDARD_DEVIATION 10.32 |
| Sex: Female, Male Female | 213 Participants | 196 Participants | 409 Participants |
| Sex: Female, Male Male | 190 Participants | 202 Participants | 392 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 403 | 50 / 398 |
| serious Total, serious adverse events | 7 / 403 | 5 / 398 |
Outcome results
Primary
Hemoglobin A1c (HbA1c) Change From Baseline to Week 18
Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus sitagliptin added on to metformin at Week 18 (Per Protocol Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.
Time frame: Baseline, Week 18
Population: Randomized participants who completed the 18 weeks of treatment had both baseline and week 18 HbA1c measurement and had no significant protocol deviations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxa + Met | Hemoglobin A1c (HbA1c) Change From Baseline to Week 18 | Baseline | 7.68 Percent | Standard Error 0.052 |
| Saxa + Met | Hemoglobin A1c (HbA1c) Change From Baseline to Week 18 | Week 18 | 7.16 Percent | Standard Error 0.052 |
| Saxa + Met | Hemoglobin A1c (HbA1c) Change From Baseline to Week 18 | Adjusted Change from Baseline | -0.52 Percent | Standard Error 0.039 |
| Sita + Met | Hemoglobin A1c (HbA1c) Change From Baseline to Week 18 | Baseline | 7.69 Percent | Standard Error 0.047 |
| Sita + Met | Hemoglobin A1c (HbA1c) Change From Baseline to Week 18 | Week 18 | 7.07 Percent | Standard Error 0.051 |
| Sita + Met | Hemoglobin A1c (HbA1c) Change From Baseline to Week 18 | Adjusted Change from Baseline | -0.62 Percent | Standard Error 0.038 |
95% CI: [-0.01, 0.2]
Secondary
Fasting Plasma Glucose Change From Baseline to Week 18 (mg/dL)
Adjusted mean change from baseline in Fasting Plasma Glucose achieved with saxagliptin added on to metformin versus sitagliptin added on to metformin at Week 18 (Full Analysis Set). Fasting Plasma Glucose is a continuous measure, the change from baseline for each participant is calculated as the Week 18 (LOCF) value minus the baseline value.
Time frame: Baseline, Week 18 (Last Observation Carried Forward)
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 18 LOCF, participants must have had a baseline and at least 1 post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxa + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mg/dL) | Baseline | 159.67 mg/dL | Standard Error 2.28 |
| Saxa + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mg/dL) | Week 18 | 149.04 mg/dL | Standard Error 1.991 |
| Saxa + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mg/dL) | Adjusted Change from Baseline | -10.75 mg/dL | Standard Error 1.455 |
| Sita + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mg/dL) | Baseline | 160.22 mg/dL | Standard Error 2.192 |
| Sita + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mg/dL) | Week 18 | 143.94 mg/dL | Standard Error 1.864 |
| Sita + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mg/dL) | Adjusted Change from Baseline | -16.16 mg/dL | Standard Error 1.464 |
95% CI: [1.37, 9.47]
Secondary
Fasting Plasma Glucose Change From Baseline to Week 18 (mmol/L)
Adjusted mean change from baseline in Fasting Plasma Glucose achieved with saxagliptin added on to metformin versus sitagliptin added on to metformin at Week 18 (Full Analysis Set). Fasting Plasma Glucose is a continuous measure, the change from baseline for each participant is calculated as the Week 18 (LOCF) value minus the baseline value.
Time frame: Baseline, Week 18 (Last Observation Carried Forward)
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 18 LOCF, participants must have had a baseline and at least 1 post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxa + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mmol/L) | Baseline | 8.86 mmol/L | Standard Error 0.127 |
| Saxa + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mmol/L) | Week 18 | 8.27 mmol/L | Standard Error 0.111 |
| Saxa + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mmol/L) | Adjusted Change from Baseline | -0.60 mmol/L | Standard Error 0.081 |
| Sita + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mmol/L) | Baseline | 8.89 mmol/L | Standard Error 0.122 |
| Sita + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mmol/L) | Week 18 | 7.99 mmol/L | Standard Error 0.103 |
| Sita + Met | Fasting Plasma Glucose Change From Baseline to Week 18 (mmol/L) | Adjusted Change from Baseline | -0.90 mmol/L | Standard Error 0.081 |
95% CI: [0.08, 0.53]
Secondary
Proportion of Patients Achieving Therapeutic Glycaemic Response Defined as HbA1c <= 6.5% at Week 18
Proportion of Patients Achieving Therapeutic Glycaemic Response Defined as HbA1c \<= 6.5% at Week 18 (Full Analysis Set)
Time frame: Week 18 (Last Observation Carried Forward)
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in the Week 18 LOCF analysis, participants must have had a baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxa + Met | Proportion of Patients Achieving Therapeutic Glycaemic Response Defined as HbA1c <= 6.5% at Week 18 | 26.3 Percentage of Participants |
| Sita + Met | Proportion of Patients Achieving Therapeutic Glycaemic Response Defined as HbA1c <= 6.5% at Week 18 | 29.1 Percentage of Participants |
95% CI: [-9, 3.5]