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.

Phase 4TerminatedNCT03152084

AstraZeneca24 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 2 Kidney Function Tests

Interventions

DapagliflozinDRUG

The study consists of a 2-week, open label, dapagliflozin (10mg) treatment period.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (4)

Research Site

Almelo, Netherlands

Research Site

Amsterdam, Netherlands

Research Site

Örebro, Sweden

Research Site

Stockholm, Sweden

Outcomes

Primary Outcomes

Change in 24-hour Sodium Excretion From Baseline to Start of Treatment

Change in 24-hour sodium excretion during dapagliflozin treatment between baseline and average of Days 2 to 4 within each study group in patients with T2DM with preserved kidney function and in non-diabetics with impaired kidney function was assessed.

Time frame: From baseline (Day -3 to Day -1) to start of treatment (Day 2 to Day 4)

Secondary Outcomes

Change in 24-hour Sodium Excretion From Baseline to End of Treatment and From End of Treatment to Follow-up

Average change in 24-hour sodium excretion from average baseline values to average end of treatment values (Day 12 to 14); and from average end of treatment values (Day 12 to 14) to average values during follow-up (Day 15 to 17).

Time frame: From baseline (Day -3 to Day -1) to end of treatment (Day 12 to 14); and from end of treatment (Day 12 to 14) to follow-up (Day 15 to 17)

Change in 24-hour Glucose Excretion From Baseline to Start of Treatment

Average change in 24-hour glucose excretion from average baseline values to average start of treatment values (Day 2 to 4).

Time frame: From baseline (Day -3 to Day -1) to start of treatment (Day 2 to 4)

Change in 24-hour Glucose Excretion From Baseline to End of Treatment

Average change in 24-hour glucose excretion from average baseline values to average end of treatment values (Day 12 to 14)

Time frame: From baseline (Day -3 to Day -1) to end of treatment (Day 12 to 14)

Change in 24-hour Glucose Excretion From End of Treatment to Follow-up

Average change in 24-hour glucose excretion from average end of treatment values (Day 12 to 14) to average values during follow-up (Day 15 to 17).

Time frame: From end of treatment (Day 12 to 14) to follow-up (Day 15 to 17)

Data from ClinicalTrials.gov

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