Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this clinical research study is to determine whether dapagliflozin can improve (decrease) blood glucose values in patients with Type 2 diabetes and moderate renal impairment.This study will be conducted at approximately 100 centres from countries across North America and European regions. It is planned to randomize a total of 302 patients.
Interventions
DRUGDapagliflozin 10 mg
Tablets administered orally once daily for 24 weeks. Randomization will be stratified by pre-enrolment anti-hyperglycemic therapy
DRUGMatching Placebo for Dapagliflozin
Matching Placebo for Dapagliflozin tablets administered orally once daily for 24 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Female or male aged ≥18 years and \<75 years. * History of T2DM for more than 12 months. * Inadequate glycemic control, defined as HbA1c ≥7.0% and ≤11% * Stable anti-diabetic treatment regimen * Renal impairment: CKD 3A
Exclusion criteria
* Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period. * History of diabetic ketoacidosis or hyperosmolar nonketotic coma. * Severe uncontrolled hypertension defined as SBP ≥180 mmHg and/or Diastolic Blood Pressure (DBP) ≥110 mmHg * Any of the following Cardiovascular (CV)/Vascular Diseases within 3 months of prior to signing the consent at visit 1: Myocardial infarction, Cardiac surgery or revascularization(CABG/PTCA), Unstable angina, Unstable heart failure (HF), HF New York Heart Association (NYHA) Class IV,Transient ischemic attack (TIA) or significant cerebrovascular disease, Unstable or previously undiagnosed arrhythmia. * History of any biopsy or imaging verifying intercurrent kidney disease (such as glomerular nephritis or sign of renal artery stenosis) other than diabetic nephropathy or diabetic nephropathy with nephrosclerosis. * Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency. * Ongoing treatment with any SGLT2-inhibitor, GLP-1 analogue, or rapid/short acting insulins at screening. * Participation in another clinical study with an Investigational Product (IP) during the last 30 days prior to signing the consent at visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 | Baseline, Week 24 | To compare the mean change from baseline in HbA1c between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m\^2). The number analyzed (142 dapaglifozin, 134 placebo) represents the number with change from baseline available at Week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24. | Baseline, Week 24 | To compare the mean percent change from baseline in total body weight between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m\^2). The number analyzed represents the number with change from baseline available at Week 24. |
| Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24. | Baseline, Week 24 | To compare the mean change from baseline in FPG between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m\^2). The number analyzed represents the number with change from baseline available at Week 24. |
| Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24. | Baseline, Week 24 | To compare the mean change from baseline in seated systolic blood pressure (SBP) between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m\^2). The number analyzed represents the number with change from baseline available at Week 24. |
Countries
Bulgaria, Canada, Czechia, Italy, Poland, Spain, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dapagliflozin 10mg QD 10 mg Tablets, Oral, Once daily, 24 weeks | 160 |
| Placebo Matching Placebo, 10 mg Tablets, Oral, Once daily, 24 weeks | 161 |
| Total | 321 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Other Eligibility criteria | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Dapagliflozin 10mg QD |
|---|---|---|---|
| Age, Continuous | 66.2 Years STANDARD_DEVIATION 6.49 | 65.8 Years STANDARD_DEVIATION 6.36 | 65.3 Years STANDARD_DEVIATION 6.22 |
| Age, Customized < 65 Years | 46 Participants | 110 Participants | 64 Participants |
| Age, Customized >= 65 Years | 115 Participants | 211 Participants | 96 Participants |
| Body Mass Index | 31.6 kg/m^2 STANDARD_DEVIATION 5 | 32.1 kg/m^2 STANDARD_DEVIATION 4.9 | 32.6 kg/m^2 STANDARD_DEVIATION 4.7 |
| Estimated Glomular Filtration Rate (eGFR) | 51.6 mL/min/1.73 m^2 STANDARD_DEVIATION 3.8 | 51.7 mL/min/1.73 m^2 STANDARD_DEVIATION 3.9 | 51.8 mL/min/1.73 m^2 STANDARD_DEVIATION 4.1 |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 13 Participants | 5 Participants |
| Race/Ethnicity, Customized Black Or African American | 12 Participants | 23 Participants | 11 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 140 Participants | 281 Participants | 141 Participants |
| Sex: Female, Male Female | 70 Participants | 139 Participants | 69 Participants |
| Sex: Female, Male Male | 91 Participants | 182 Participants | 91 Participants |
| Urine Albumin-to-Creatinine Ratio (UACR) | 246.52 mg/g STANDARD_DEVIATION 775.49 | 236.78 mg/g STANDARD_DEVIATION 678.81 | 226.91 mg/g STANDARD_DEVIATION 566.67 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 160 | 0 / 161 |
| other Total, other adverse events | 0 / 160 | 0 / 161 |
| serious Total, serious adverse events | 9 / 160 | 14 / 161 |
Outcome results
Primary
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24
To compare the mean change from baseline in HbA1c between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m\^2). The number analyzed (142 dapaglifozin, 134 placebo) represents the number with change from baseline available at Week 24.
Time frame: Baseline, Week 24
Population: For glycaemic measurements (HbA1c and FPG), all measurements after the first dose of rescue medication were excluded. For other non-glycaemic measurements (body weight and SBP), all measurements after the first dose of rescue medication were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 | -0.37 percent | Standard Error 0.1 |
| Placebo | Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 | -0.03 percent | Standard Error 0.1 |
Comparison: Difference in adjusted mean change from baseline (MMRM model)p-value: <0.00195% CI: [-0.53, -0.15]Mixed Models Analysis
Secondary
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24.
To compare the mean change from baseline in FPG between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m\^2). The number analyzed represents the number with change from baseline available at Week 24.
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24. | -21.46 mg/dL | Standard Error 5.2 |
| Placebo | Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24. | -4.87 mg/dL | Standard Error 5.13 |
Comparison: Difference in adjusted mean change from baseline versus placebo (MMRM)p-value: 0.00195% CI: [-26.73, -6.45]Mixed Models Analysis
Secondary
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24.
To compare the mean change from baseline in seated systolic blood pressure (SBP) between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m\^2). The number analyzed represents the number with change from baseline available at Week 24.
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24. | -4.8 mmHg | Standard Error 1.5 |
| Placebo | Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24. | -1.7 mmHg | Standard Error 1.5 |
Comparison: Difference in adjusted mean change from baseline vs. placebo (MMRM)p-value: <0.0595% CI: [-6.3, 0]Mixed Models Analysis
Secondary
Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24.
To compare the mean percent change from baseline in total body weight between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m\^2). The number analyzed represents the number with change from baseline available at Week 24.
Time frame: Baseline, Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin | Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24. | -3.42 percent change | Standard Error 0.32 |
| Placebo | Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24. | -2.02 percent change | Standard Error 0.32 |
Comparison: Difference in adjusted mean percent change from baseline (MMRM)p-value: <0.00195% CI: [-2.15, -0.69]Mixed Models Analysis