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

AstraZeneca

Status and phase: Completed; Phase 3; Phase 2

Conditions: Type 2 Diabetes Mellitus, CKD and Albuminuria

Treatments: Drug: Saxagliptin 2.5 mg; Drug: Dapagliflozin 10 mg; Drug: Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02547935

D1690C00023

Details and patient eligibility

About

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)

Enrollment: 459 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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459 participants in 3 patient groups, including a placebo group

Dapagliflozin 10mg

Experimental group

Description:

Tablets administered orally once daily for 24 weeks

Treatment:

Drug: Dapagliflozin 10 mg

Dapagliflozin 10mg + Saxagliptin 2.5mg

Experimental group

Description:

Tablets administered orally once daily for 24 weeks

Treatment:

Drug: Saxagliptin 2.5 mg

Placebo

Placebo Comparator group

Description:

Tablets administered orally once daily for 24 weeks

Treatment:

Drug: Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg