A study to evaluate the efficacy and safety of dapagliflozin and dapagliflozinin combination with saxagliptin in type 2 diabetes with kidney disease.

Phase 1

Conditions: CKD3 patients with type 2 diabetes mellitus and albuminuria.
MedDRA version: 18.0Level: LLTClassification code 10045250Term: Type II diabetes mellitus with renal manifestationsSystem Organ Class: 100000004857
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2015-002676-24-ES

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1125

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures 2. Female or male aged > o = 18 years and < 75 years. 3. History of type 2 diabetes mellitus for more than 12 months 4. Inadequate glycemic control, defined as HbA1c > o = 7.5% and < o = 10.5%. 5. Stable antidiabetic treatment during the last 12 weeks up to randomization.Stable antidiabetic treatment regimen, defined as: Stable diet and exercise therapy alone or in combination with any or both of the two following alternatives a.A regimen of any approved oral anti-diabetic medication (except SGLT2 inhibitors, GLP-1 receptor agonists and DPP4 inhibitors) where no dosechanges have occurred during the last 12 weeks up to randomization. b.Long acting or intermediate acting insulin and mixed insulin permitted as long as the dose is stable 12 weeks before randomization, changes ± 10% are allowed (in relation to number of units at randomization). 6. Renal impairment defined as eGFR 30 - 59 mL/minute/1.73 m^2, inclusive. 7. Micro or macroalbuminuria (UACR 30 - 3500 mg/g, inclusive). 8. Patient must be receiving an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) for at least 3 months prior to screening, where the dose of the ACE inhibitor or the ARB is considered appropriate for that patient, and has been stable and maintained on that dose for at least 4 weeks prior to study randomization.
9. Body mass index between 20 and 40 kg/m^2, inclusive.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 225
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 225

Exclusion Criteria

Main exclusion criteria are:- History of ?2 major hypoglycaemic events in the 3 months prior to enrolment visit, defined as symptomatic events
requiring external assistance due to severe impairment in consciousness or behaviour, with blood glucose level <3.0 mmol/L, <54 mg/dL (plasma glucose level <3.5 mmol/L, <63 mg/dL) and prompt recovery after glucose or glucagon administration.- Patients with Type 1 DM, history of diabetes insipidus, diabetic ketoacidosis, hyperosmolar nonketotic coma- Severe uncontrolled hypertension or any CV/Vascular Diseases within 3 month prior to signing the following: - Myocardial infarction. - Cardiac surgery or revascularization.- Unstable angina.- Unstable heart failure.- HF
New York Heart Association Class III-IV.- Transient ischemic attack or
significant cerebrovascular disease.- Unstable or previously undiagnosed arrhythmia.-Significant hepatic disease, severe hepatobiliary disease or hepatotoxicity with any medication- History of haemoglobinopathy or acute kidney injury requiring renal replacement therapy or any biopsy or imaging verifying intercurrent kidney disease other than diabetic nephropathy or diabetic nephropathy with nephrosclerosis.- History of unexplained microscopic or gross haematuria, or microscopic haematuria, confirmed by a follow-up sample at next scheduled visit- Treatment with a SGLT2 inhibitor, GLP-1 agonist or DPP4 inhibitors.- Simultaneous treatment with both an ACEi and an ARB- A metformin dose which is outside the specified dose range for moderate renal impairment (eGFR 30-59 mL/minute/1.73 m^2,) according to local guidelines and investigators judgement.- Any condition which, in the ju gment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk or suspected risk to the patient or with confirmed poor protocol or medication compliance - Patients at risk for volume depletion as judged by the investigator.