Phase 3
N=448
A Study to Evaluate the Effect of Dapagliflozin With and Without Saxagliptin on Albuminuria, and to Investigate the Effect of Dapagliflozin and Saxagliptin on HbA1c in Patients With Type 2 Diabetes and CKD
Type 2 Diabetes Mellitus, CKD and Albuminuria
Bottom Line
View on ClinicalTrials.gov: NCT02547935 ↗Enrolled (actual)
448
Serious AEs
9.0%
Results posted
Jun 2019
Primary outcome: Primary: Adjusted Mean Change From Baseline in Glycosylated Haemoglobin (HbA1c): Comparison of Dapagliflozin 10 mg Plus Saxagliptin 2.5 mg and Placebo at Week 24 — -0.85; -0.27 Percentage of Glycoslyated HbA1c — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Dapagliflozin 10 mg (Drug); Saxagliptin 2.5 mg (Drug); Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- May 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Adjusted Mean Change From Baseline in Glycosylated Haemoglobin (HbA1c): Comparison of Dapagliflozin 10 mg Plus Saxagliptin 2.5 mg and Placebo at Week 24 |
-0.85; -0.27 | <0.001 sig |
| PRIMARY Adjusted Mean Percent Change From Baseline in Urine Albumin-to-Creatinine Ratio (UACR) at Week 24 |
-39.1; -22.4; -1.8 | <0.001 sig |
| SECONDARY Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24 |
-0.65; -1.48; -0.61 | 0.953 |
| SECONDARY Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 |
-17.2; -13.1; -11.2 | 0.298 |
| SECONDARY Percentage of Patients Achieving at Least 30% Reduction in UACR at Week 24 |
57.0; 45.0; 31.3 | <0.001 sig |
| SECONDARY Percentage of Patients Achieving a Reduction in HbA1c of Less Than 7.0% at Week 24 |
35.1; 15.0; 10.3 | <0.001 sig |
| SECONDARY Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24 |
-8.8; -6.9; -4.1 | 0.009 sig |
| SECONDARY Adjusted Mean Change From Baseline in HbA1c: Comparison of Dapagliflozin 10 mg and Placebo at Week 24 |
-0.43; -0.27 | 0.142 |
Summary
The purpose of this clinical research study is to determine whether dapagliflozin alone or in combination with saxagliptin can decrease albuminuria and improve glycemic control in patients with Type 2 diabetes, albuminuria and renal impairment (CKD). The study is planned to randomize a total of 450 patients (150 patients per treatment arm)
Eligibility Criteria
Inclusion Criteria
- Provision of informed consent prior to any study specific procedures
- Female or male aged ≥18 years
- History of type 2 diabetes mellitus for more than 12 months
- HbA1c≥7.0% and ≤11.0%
- Stable antidiabetic treatment during the last 12 weeks up to randomization
- eGFR 25-75 mL/minute/1.73m2, inclusive
- Micro or macroalbuminuria (UACR 30 - 3500 mg/g)
- Treatment with ACE inhibitor or an ARB for at least 3 months prior to screening
- Body mass index between 20 and 45 kg/m2
Exclusion Criteria
- Any of the following CV/Vascular Diseases within 3 month prior to signing the consent at Visit 1:
- Myocardial infarction
- cardiac surgery or revascularization (CABG/PTCA)
- unstable angina
- unstable HF
- New York Heart Association (NYHA) Class III-IV
- transient ischemic attack (TIA) or significant cerebrovascular disease
- unstable or previously undiagnosed arrhythmia
- Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency
- Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 3X ULN
- Total Bilirubin (TB) >2 mg/dL (34.2 μmol/L)
- History of acute kidney injury requiring renal replacement therapy (dialysis or ultrafiltration) or any biopsy or imaging verifying intercurrent kidney disease other than diabetic nephropathy or diabetic nephropathy with nephrosclerosis
- Ongoing treatment with a SGLT2 inhibitor, GLP-1 agonist or DPP4 inhibitors
- Any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient or patient suspected or with confirmed poor protocol or medication compliance
Data sourced from ClinicalTrials.gov (NCT02547935). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.