Type 2 Diabetes
Conditions
Keywords
DPP-4 inhibitors, HBA1c, Incretins
Brief summary
Saxagliptin is a new investigational medication being developed for treatment of type 2 diabetes. This study is designed to evaluate the efficacy and safety in adult patients with inadequate glycaemic control with diet and exercise.
Interventions
DRUGSaxagliptin
5mg, oral tablet, once daily for 24 weeks
DRUGPlacebo
oral tablet, once daily for 24 weeks
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 * Patients should be drug naïve ie, not received medical treatment for diabetes, * HbA1c ≥ 7.2% and ≤10.0% (at enrolment), HbA1c ≥ 7.0% and ≤10.0% (at randomization)
Exclusion criteria
* Insulin therapy within one year of enrolment (with the exception of insulin therapy during a hospitalization or use in gestational diabetes), * Type 1 diabetes,history of ketoacidosis or hyperosmolar non-ketonic koma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) | Baseline , Week 24 | Adjusted\* mean change from baseline in HbA1c achieved with saxagliptin 5 mg versus placebo at week 24 (LOCF, Full Analysis set). HbA1c is a continuous measure, the change from baseline for each subject is calculated as the week 24 values minus the baseline value. HbA1c data were excluded on and after rescue medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change (mmol/L) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Baseline, Week 24 | Adjusted\* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 5 mg versus placebo at week 24 (Last Observation Carried Forward (LOCF), Full Analysis set). FPG is a continuous measure, the change from baseline for each subject is calculated as the week 24 values minus the baseline value. FPG data were excluded on and after rescue medication. |
| Absolute Change (mg/dL) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Baseline, Week 24 | Adjusted\* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 5 mg versus placebo at week 24 (LOCF, Full Analysis set). FPG is a continuous measure, the change from baseline for each subject is calculated as the week 24 values minus the baseline value. FPG data were excluded on and after rescue medication. |
| Absolute Change (mmol*Min/L) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Baseline , Week 24 | Adjusted\* mean change from baseline in PPG AUC achieved with saxagliptin 5 mg versus placebo at week 24 (LOCF, Full Analysis set). Trapezoidal method was used to compute AUC under the 3 hour PPG curve. Change from baseline for each subject is computed as the week 24 value minus the baseline value.PPG data were excluded on and after rescue medication |
| Absolute Change (mg*Min/dL) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Baseline , Week 24 | Adjusted\* mean change from baseline in PPG AUC achieved with saxagliptin 5 mg versus placebo at week 24 (LOCF, Full Analysis set). Trapezoidal method was used to compute AUC under the 3 hour PPG curve. Change from baseline for each subject is computed as the week 24 value minus the baseline value.PPG data were excluded on and after rescue medication |
| Proportion of Patients Achieving a Therapeutic Glycemic Response Defined as HbA1c <7.0% at Week 24 | Baseline, Week 24 | Proportion of participants (expressed in percentage of total participants) achieving HbA1c \< 7.0% for saxagliptin versus placebo at week 24. HbA1c Data were excluded on and after rescue medication |
Countries
China, India, Philippines, South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Saxagliptin 5 mg Saxagliptin 5 mg tablet, once daily (OD) for 24 weeks | 284 |
| Placebo Placebo tablet, once daily( OD) for 24 weeks | 284 |
| Total | 568 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Incorrect enrollment | 0 | 2 |
| Overall Study | Lost to Follow-up | 6 | 1 |
| Overall Study | Safety reasons | 0 | 2 |
| Overall Study | Severe non-compliance to protocol | 1 | 2 |
| Overall Study | Study specific discontinuation criteria | 3 | 4 |
| Overall Study | Withdrawal by Subject | 11 | 23 |
Baseline characteristics
| Characteristic | Saxagliptin 5 mg | Placebo | Total |
|---|---|---|---|
| Age Continuous | 51.23 Years STANDARD_DEVIATION 10.04 | 51.57 Years STANDARD_DEVIATION 10.34 | 51.4 Years STANDARD_DEVIATION 10.18 |
| Sex: Female, Male Female | 124 Participants | 129 Participants | 253 Participants |
| Sex: Female, Male Male | 160 Participants | 155 Participants | 315 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 284 | 22 / 284 |
| serious Total, serious adverse events | 8 / 284 | 4 / 284 |
Outcome results
Primary
Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c)
Adjusted\* mean change from baseline in HbA1c achieved with saxagliptin 5 mg versus placebo at week 24 (LOCF, Full Analysis set). HbA1c is a continuous measure, the change from baseline for each subject is calculated as the week 24 values minus the baseline value. HbA1c data were excluded on and after rescue medication.
Time frame: Baseline , Week 24
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Wk 24 LOCF for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. If participant received rescue medication, that measurement must have been taken before rescue.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin 5 mg | Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) | Baseline | 8.15 percent | Standard Error 0.05 |
| Saxagliptin 5 mg | Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) | Week 24 | 7.25 percent | Standard Error 0.063 |
| Saxagliptin 5 mg | Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) | Adjusted Mean Change from Baseline | -0.84 percent | Standard Error 0.067 |
| Placebo | Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) | Baseline | 8.14 percent | Standard Error 0.05 |
| Placebo | Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) | Week 24 | 7.75 percent | Standard Error 0.076 |
| Placebo | Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) | Adjusted Mean Change from Baseline | -0.34 percent | Standard Error 0.065 |
p-value: <0.000195% CI: [-0.65, -0.34]ANCOVA
Secondary
Absolute Change (mg/dL) From Baseline to Week 24 in Fasting Plasma Glucose (FPG)
Adjusted\* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 5 mg versus placebo at week 24 (LOCF, Full Analysis set). FPG is a continuous measure, the change from baseline for each subject is calculated as the week 24 values minus the baseline value. FPG data were excluded on and after rescue medication.
Time frame: Baseline, Week 24
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Wk 24 LOCF for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. If participant received rescue medication, that measurement must have been taken before rescue.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin 5 mg | Absolute Change (mg/dL) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Baseline | 164.85 mg/dL | Standard Error 2.253 |
| Saxagliptin 5 mg | Absolute Change (mg/dL) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Week 24 | 145.97 mg/dL | Standard Error 2.317 |
| Saxagliptin 5 mg | Absolute Change (mg/dL) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Adjusted mean change from Baseline | -16.13 mg/dL | Standard Error 2.586 |
| Placebo | Absolute Change (mg/dL) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Baseline | 163.03 mg/dL | Standard Error 2.543 |
| Placebo | Absolute Change (mg/dL) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Week 24 | 158.04 mg/dL | Standard Error 2.942 |
| Placebo | Absolute Change (mg/dL) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Adjusted mean change from Baseline | -3.01 mg/dL | Standard Error 2.544 |
p-value: <0.000195% CI: [-19.12, -7.13]ANCOVA
Secondary
Absolute Change (mg*Min/dL) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants
Adjusted\* mean change from baseline in PPG AUC achieved with saxagliptin 5 mg versus placebo at week 24 (LOCF, Full Analysis set). Trapezoidal method was used to compute AUC under the 3 hour PPG curve. Change from baseline for each subject is computed as the week 24 value minus the baseline value.PPG data were excluded on and after rescue medication
Time frame: Baseline , Week 24
Population: MMTT was measured on a subset of patients in China cohort only at baseline and Wk 24. Randomized subjects, who took at least 1 dose of double-blind treatment to be included in analysis: change from baseline to Wk 24 (LOCF), must have had baseline and post-baseline data. Measurements observed on and after rescue medication were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin 5 mg | Absolute Change (mg*Min/dL) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | week 24 | 37166 mg*min/dL | Standard Error 739.6 |
| Saxagliptin 5 mg | Absolute Change (mg*Min/dL) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Adjusted mean change from Baseline | -7534 mg*min/dL | Standard Error 657.4 |
| Saxagliptin 5 mg | Absolute Change (mg*Min/dL) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Baseline | 44586 mg*min/dL | Standard Error 844.8 |
| Placebo | Absolute Change (mg*Min/dL) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | week 24 | 40751 mg*min/dL | Standard Error 1036.6 |
| Placebo | Absolute Change (mg*Min/dL) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Adjusted mean change from Baseline | -4255 mg*min/dL | Standard Error 726.4 |
| Placebo | Absolute Change (mg*Min/dL) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Baseline | 45146 mg*min/dL | Standard Error 1170.5 |
p-value: 0.00195% CI: [-5214, -1345]ANCOVA
Secondary
Absolute Change (mmol/L) From Baseline to Week 24 in Fasting Plasma Glucose (FPG)
Adjusted\* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 5 mg versus placebo at week 24 (Last Observation Carried Forward (LOCF), Full Analysis set). FPG is a continuous measure, the change from baseline for each subject is calculated as the week 24 values minus the baseline value. FPG data were excluded on and after rescue medication.
Time frame: Baseline, Week 24
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Wk 24 LOCF for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. If participant received rescue medication, that measurement must have been taken before rescue.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin 5 mg | Absolute Change (mmol/L) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Baseline | 9.15 mmol/L | Standard Error 0.125 |
| Saxagliptin 5 mg | Absolute Change (mmol/L) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | week 24 | 8.10 mmol/L | Standard Error 0.129 |
| Saxagliptin 5 mg | Absolute Change (mmol/L) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Adjusted mean change from Baseline | -0.90 mmol/L | Standard Error 0.144 |
| Placebo | Absolute Change (mmol/L) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Baseline | 9.05 mmol/L | Standard Error 0.141 |
| Placebo | Absolute Change (mmol/L) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | week 24 | 8.77 mmol/L | Standard Error 0.163 |
| Placebo | Absolute Change (mmol/L) From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Adjusted mean change from Baseline | -0.17 mmol/L | Standard Error 0.141 |
p-value: <0.000195% CI: [-1.06, -0.39]ANCOVA
Secondary
Absolute Change (mmol*Min/L) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants
Adjusted\* mean change from baseline in PPG AUC achieved with saxagliptin 5 mg versus placebo at week 24 (LOCF, Full Analysis set). Trapezoidal method was used to compute AUC under the 3 hour PPG curve. Change from baseline for each subject is computed as the week 24 value minus the baseline value.PPG data were excluded on and after rescue medication
Time frame: Baseline , Week 24
Population: MMTT was measured on a subset of patients in China cohort only at baseline and Wk 24. Randomized subjects, who took at least 1 dose of double-blind treatment to be included in analysis: change from baseline to Wk 24 (LOCF), must have had baseline and post-baseline data. Measurements observed on and after rescue medication were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin 5 mg | Absolute Change (mmol*Min/L) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Adjusted mean change from Baseline | -417 mmol*min/L | Standard Error 36.5 |
| Saxagliptin 5 mg | Absolute Change (mmol*Min/L) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Baseline | 2474 mmol*min/L | Standard Error 46.9 |
| Saxagliptin 5 mg | Absolute Change (mmol*Min/L) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Week 24 | 2063 mmol*min/L | Standard Error 41.1 |
| Placebo | Absolute Change (mmol*Min/L) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Baseline | 2506 mmol*min/L | Standard Error 64.9 |
| Placebo | Absolute Change (mmol*Min/L) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Week 24 | 2262 mmol*min/L | Standard Error 57.6 |
| Placebo | Absolute Change (mmol*Min/L) From Baseline to Week 24 in Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During Mixed Meal (Instant Noodles) Tolerance Tests (MMTT) in All MMTT Participants | Adjusted mean change from Baseline | -235 mmol*min/L | Standard Error 40.4 |
p-value: 0.00195% CI: [-289, -74]ANCOVA
Secondary
Proportion of Patients Achieving a Therapeutic Glycemic Response Defined as HbA1c <7.0% at Week 24
Proportion of participants (expressed in percentage of total participants) achieving HbA1c \< 7.0% for saxagliptin versus placebo at week 24. HbA1c Data were excluded on and after rescue medication
Time frame: Baseline, Week 24
Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Wk 24 LOCF for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. If participant received rescue medication, that measurement must have been taken before rescue.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin 5 mg | Proportion of Patients Achieving a Therapeutic Glycemic Response Defined as HbA1c <7.0% at Week 24 | 45.8 Percentage of Participants |
| Placebo | Proportion of Patients Achieving a Therapeutic Glycemic Response Defined as HbA1c <7.0% at Week 24 | 28.8 Percentage of Participants |
p-value: <0.000195% CI: [8.9, 24.9]ANCOVA