The Study Will Evaluate Average 24-hr Sodium Excretion During Dapagliflozin Treatment in Patients With Type 2 Diabetes Mellitus With Preserved or Impaired Renal Function or Non-diabetics With Impaired Renal Function. (DAPASALT)

AstraZeneca

Status and phase: Terminated; Phase 4

Conditions: Kidney Function Tests; Diabetes Mellitus, Type 2

Treatments: Drug: Dapagliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03152084

D1690C00049

2016-002961-79 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate how dapagliflozin mechanism of action is impacted by Type 2 Diabetes Mellitus status and kidney function

Enrollment: 24 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Provision of signed and dated, written informed consent prior to any study specific procedures
• Female and/or male aged between 18 years and ≤80 years
• In the diabetic arms - a diagnosis of T2DM with HbA1c ≥6.5% (≥48 mmol/mol) and <10% (<86 mmol/mol); and eGFR (CKD-EPI) between ≥25 and ≤50 mL/min/1.73m2 or between >90 and ≤130 mL/min/1.73m2 for patients aged 59 years or younger, between >85 and ≤130 mL/min/1.73m2 for patients aged 60 to 69 years, and between >75 and ≤130 mL/min/1.73m2 for patients aged 70 years or older at the Screening Visit (Visit 1)
• In the non-diabetic arm, HbA1c <6.5% (<48 mmol/mol) and an eGFR (CKD-EPI) between ≥25 and ≤50 mL/min/1.73m2 at the Screening Visit (Visit 1)
• Patient specific optimal antihypertensive dose of an angiotensin receptor blocker at least 6 weeks before study treatment
• In the diabetic arm (Group 2) an appropriate stable dose of metformin, or sulphonylurea, or metformin+sulphonylurea as anti-diabetic therapy for the last 12 weeks before study treatment
• Stable urinary sodium excretion on 2 successive 24-hr urinary sodium excretion measurements.
• In the diabetic arm with impaired renal function (Group 1), a stable insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) for the last 12 weeks prior to Visit 4 (Day 1), as judged by the Investigator. Metformin or sulphonylurea, or metformin+sulphonylurea together with insulin would be accepted, but is not mandatory. If used, stable dose of metformin or sulphonylurea, or metformin+sulphonylurea as anti-diabetic therapy for the last 12 weeks prior to Visit 4 (Day 1) is required.

Exclusion criteria

• Diagnosis of Type 1 Diabetes Mellitus
• Any of the following cardiovascular/vascular diseases within 3 months prior to signing the consent; myocardial infarction, cardiac surgery or revascularization, unstable angina, unstable heart failure, heart failure NYHA Class IV, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia
• Symptoms/complaints suggestive of established neurogenic bladder and/or incomplete bladder emptying
• History of bladder cancer, diagnosis of polycystic kidney disease, history or current lupus nephritis or unstable or rapidly progressing renal disease
• UACR >1000 mg/g at screening
• Current/chronic use of the following medications: any anti-diabetic medication with the exception of metformin, sulphonylurea, angiotensin converting enzyme inhibitors, insulin (insulin only allowed in Group 1), oral glucocorticoids, non-steroidal anti-inflammatory drugs, immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants and monoamine oxidase inhibitors
• Receiving immunosuppressive or other immunotherapy for primary or secondary renal disease within 6 months prior to screening
• Current treatment or treatment within the last 2 weeks prior to screening with diuretics including loop diuretics, thiazides, and mineralocorticoid antagonists

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Arm 1

Experimental group

Description:

T2DM subjects with an eGFR (CKD-EPI) between ≥25 and ≤50 mL/min/1.73m2 at the Screening Visit.

Treatment:

Drug: Dapagliflozin

Arm 2

Experimental group

Description:

T2DM subjects with an eGFR (CKD-EPI) between \>90 and ≤130 mL/min/1.73m2 for patients aged 59 or younger, between \>85 and ≤130 mL/min/1.73m2 for patients aged 60 to 69, and between \>75 and ≤130 mL/min/1.73m2 for patients aged 70 or older at the Screening Visit.

Treatment:

Drug: Dapagliflozin

Arm 3

Experimental group

Description:

Non-diabetic subjects with an eGFR (CKD-EPI) between ≥25 and ≤50 mL/min/1.73m2 at the Screening Visit.

Treatment:

Drug: Dapagliflozin