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.

Diabetes Mellitus, Type 2 Clinical Trial

— DAPASALT  

Official title:

DAPASALT: An Open Label, Phase IV, Mechanistic, Three-Arm Study to Evaluate the Natriuretic Effect of 2-Week Dapagliflozin Treatment in Type 2 Diabetes Mellitus Patients With Either Preserved or Impaired Renal Function and Non-Diabetics With Impaired Renal Function

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03152084
• Other study ID #: D1690C00049
• Secondary ID: 2016-002961-79
• Status: Terminated
• Phase: Phase 4
• Start date: July 12, 2017
• Est. completion date: March 20, 2020

Study information

• Verified date: May 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: March 20, 2020
• Est. primary completion date: March 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Kidney Function Tests
• Renal Insufficiency

Intervention

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

Locations

Country	Name	City	State
Netherlands	Research Site	Almelo
Netherlands	Research Site	Amsterdam
Sweden	Research Site	Örebro
Sweden	Research Site	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Netherlands,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From baseline (Day -3 to Day -1) to start of treatment (Day 2 to Day 4)
Secondary	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).	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)
Secondary	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).	From baseline (Day -3 to Day -1) to start of treatment (Day 2 to 4)
Secondary	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)	From baseline (Day -3 to Day -1) to end of treatment (Day 12 to 14)
Secondary	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).	From end of treatment (Day 12 to 14) to follow-up (Day 15 to 17)
Secondary	Change in Mean 24-hour Systolic Blood Pressure From Baseline to Start of Treatment	Change in mean 24-hour systolic blood pressure from baseline to start of treatment (Day 4)	From baseline (Day -1) to start of treatment (Day 4)
Secondary	Change in Mean 24-hour Systolic Blood Pressure From Baseline to End of Treatment	Change in mean 24-hour systolic blood pressure from baseline to end of treatment (Day 13).	From baseline (Day -1) to end of treatment (Day 13)
Secondary	Change in Mean 24-hour Systolic Blood Pressure From End of Treatment to End of Follow-up	Change in mean 24-hour systolic blood pressure from end of treatment (Day 13) to end of follow-up (Day 18).	From end of treatment (Day 13) to end of follow-up (Day 18)
Secondary	Change in Plasma Volume From Baseline to Start of Treatment	Change in plasma volume from baseline to start of treatment (Day 4).	From baseline (Day 1) to start of treatment (Day 4)
Secondary	Change in Plasma Volume From Baseline to End of Treatment	Change in plasma volume from baseline to end of treatment (Day 14).	From baseline (Day 1) to end of treatment (Day 14)
Secondary	Change in Plasma Volume From End of Treatment to End of Follow-up	Change in plasma volume from end of treatment (Day 14) to end of follow-up (Day 18).	From end of treatment (Day 14) to end of follow-up (Day 18)
Secondary	Change in Extracellular Volume From Baseline to Start of Treatment	Change in extracellular volume from baseline to start of treatment (Day 4).	From baseline (Day 1) to start of treatment (Day 4)
Secondary	Change in Extracellular Volume From Baseline to End of Treatment	Change in extracellular volume from baseline to end of treatment (Day 14).	From baseline (Day 1) to end of treatment (Day 14)
Secondary	Change in Extracellular Volume From End of Treatment to End of Follow-up	Change in extracellular volume from end of treatment (Day 14) to end of follow-up (Day 18).	From end of treatment (Day 14) to end of follow-up (Day 18)
Secondary	Change in 24-hour Urine Albumin:Creatinine Ratio (UACR)	Average change in mean 24-hour urine albumin:creatinine ratio (UACR) from average baseline to Day 4; and from average baseline values to average end of treatment values (Day 12 to 14).	From baseline (Day -3 to Day -1) to start of treatment (Day 4); and from baseline (Day -3 to Day-1) to end of treatment (Day 12 to 14)
Secondary	Pharmacokinetics of Dapagliflozin on Day 4 and Day 14	Dapagliflozin plasma concentration on Day 4 (pre-dose) and Day 14 (pre-dose, 1h, 2h, 4h post-dose)	At pre-dose (Day 4) and at pre-dose, 1h, 2h, 4h post-dose (Day 14)
Secondary	Number of Patients With AEs and SAEs	An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. SAE is an AE that results in any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a significant medical event.	From Day 1 until Day 18 (Follow-up)

External Links

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