Diabetes
Conditions
Brief summary
The purpose is to determine if after 24 weeks of oral daily administration, there will be a greater mean reduction from baseline in glycosylated hemoglobin (HbA1c) achieved with Dapagliflozin 10 mg plus insulin compared to placebo plus insulin in subjects with type 2 diabetes.
Interventions
DRUGDapagliflozin
Tablet
Tablet
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
* Subjects must have type 2 diabetes with inadequate glycemic control, defined as HbA1c ≥ 7.5% and ≤ 11.0% obtained at screening visit * Subjects must be taking a stable mean dose of ≥ 20 IU injectable insulin daily for at least 8 weeks prior to enrollment Inclusion criteria for randomization: HbA1c ≥ 7.5 and ≤ 10.5% at Day -14
Exclusion criteria
* Treatment with more than two oral antidiabetic (OAD) agents within 6 weeks of Enrollment * History of diabetic ketoacidosis of hyperosmolar nonketotic coma * Clinically diagnosed Type 1 diabetes mellitus * Congestive heart failure defined as New York Heart Association (NYHA) stage III and IV * Severe uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 180 mmHg and/or diastolic blood pressure (DBP) ≥ 110 mmHg * History of unstable or rapidly progressing renal disease * History of severe hepatobiliary disease * Mallingancy within 5 years of the screening/enrollment visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change in HbA1c From Baseline to Week 24 | Baseline (Day 1) and 24 weeks | The adjusted mean change in the percentage of Hemoglobin A1c (HbA1c) from baseline to Week 24 was reported for each arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24 | Baseline (Day 1) and 24 weeks | The adjusted mean change from baseline to 24 weeks in Fasting Plasma Glucose (FPG) was reported for each arm in milligrams per deciliter (mg/dL). |
| Adjusted Mean Change in Body Weight From Baseline to Week 24 | Baseline (Day 1) and 24 weeks | Adjusted mean change in body weight from baseline to week 24 was reported for each arm in kilograms (kg). |
| Adjusted Mean Change in Absolute Calculated Mean Total Daily Dose of Insulin (TDDI) From Baseline to Week 24 | Baseline (Day 1) and 24 weeks | The adjusted mean change in absolute calculated mean Total Daily Dose of Insulin (TDDI) from baseline to week 24 was reported for each arm in International Units (IU). |
Countries
China, Singapore, South Korea
Participant flow
Pre-assignment details
477 participants were enrolled; 313 entered lead-in period; 272 participants were randomized to a treatment group. Of the 205 participants not randomized to a treatment group: 190 No longer met study criteria, 11 withdrew consent, 2 were lost to follow-up, and 2 were removed for administrative reasons.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Dapagliflozin Placebo 0 mg oral Tablet once daily for 24 weeks + Background Insulin | 133 |
| Dapagliflozin Dapagliflozin 10 mg oral Tablet once daily for 24 weeks + Background Insulin | 139 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up | Adverse Event | 2 | 2 |
| Follow-up | Subjects not reporting status | 1 | 2 |
| Follow-up | Withdrawal by Subject | 1 | 0 |
| Treatment | Adverse Event | 6 | 3 |
| Treatment | Other | 1 | 1 |
| Treatment | Subject request to discontinue treatment | 1 | 1 |
| Treatment | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Dapagliflozin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 36 Participants | 22 Participants | 58 Participants |
| Age, Categorical Between 18 and 65 years | 97 Participants | 117 Participants | 214 Participants |
| Age, Continuous | 58.6 years STANDARD_DEVIATION 8.91 | 56.5 years STANDARD_DEVIATION 8.39 | 57.5 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 69 Participants | 73 Participants | 142 Participants |
| Sex: Female, Male Male | 64 Participants | 66 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 139 | 61 / 133 |
| serious Total, serious adverse events | 8 / 139 | 18 / 133 |
Outcome results
Primary
Adjusted Mean Change in HbA1c From Baseline to Week 24
The adjusted mean change in the percentage of Hemoglobin A1c (HbA1c) from baseline to Week 24 was reported for each arm.
Time frame: Baseline (Day 1) and 24 weeks
Population: All randomized participants with non-missing baseline and at least one post-baseline value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Adjusted Mean Change in HbA1c From Baseline to Week 24 | 0.03 percentage of hemoglobin | Standard Error 0.0707 |
| Dapagliflozin | Adjusted Mean Change in HbA1c From Baseline to Week 24 | -0.87 percentage of hemoglobin | Standard Error 0.0666 |
p-value: <0.000195% CI: [-1.09, -0.71]Longitudinal repeated measure analysis
Secondary
Adjusted Mean Change in Absolute Calculated Mean Total Daily Dose of Insulin (TDDI) From Baseline to Week 24
The adjusted mean change in absolute calculated mean Total Daily Dose of Insulin (TDDI) from baseline to week 24 was reported for each arm in International Units (IU).
Time frame: Baseline (Day 1) and 24 weeks
Population: All randomized participants with non-missing baseline and at least one post-baseline value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Adjusted Mean Change in Absolute Calculated Mean Total Daily Dose of Insulin (TDDI) From Baseline to Week 24 | 0.74 International Units (IU) | Standard Error 0.3723 |
| Dapagliflozin | Adjusted Mean Change in Absolute Calculated Mean Total Daily Dose of Insulin (TDDI) From Baseline to Week 24 | -0.70 International Units (IU) | Standard Error 0.3592 |
p-value: 0.005995% CI: [-2.45, -0.42]Longitudinal repeated measure analysis
Secondary
Adjusted Mean Change in Body Weight From Baseline to Week 24
Adjusted mean change in body weight from baseline to week 24 was reported for each arm in kilograms (kg).
Time frame: Baseline (Day 1) and 24 weeks
Population: All randomized participants with non-missing baseline and at least one post-baseline value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Adjusted Mean Change in Body Weight From Baseline to Week 24 | 0.37 kilograms | Standard Error 0.2224 |
| Dapagliflozin | Adjusted Mean Change in Body Weight From Baseline to Week 24 | -1.00 kilograms | Standard Error 0.2103 |
p-value: <0.000195% CI: [-1.98, -0.77]Longitudinal repeated measure analysis
Secondary
Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24
The adjusted mean change from baseline to 24 weeks in Fasting Plasma Glucose (FPG) was reported for each arm in milligrams per deciliter (mg/dL).
Time frame: Baseline (Day 1) and 24 weeks
Population: All randomized participants with non-missing baseline and at least one post-baseline value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24 | 0.07 mg/dL | Standard Error 3.3803 |
| Dapagliflozin | Adjusted Mean Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24 | -30.62 mg/dL | Standard Error 3.1314 |
p-value: <0.000195% CI: [-39.76, -21.61]Longitudinal repeated measure analysis