Clinical trial NCT03152084: 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.
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Kidney Function Tests
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2017-05-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: Change in 24-hour Sodium Excretion From Baseline to Start of Treatment
timeFrame: From baseline (Day -3 to Day -1) to start of treatment (Day 2 to Day 4)
Secondary outcomes:
measure: Change in 24-hour Sodium Excretion From Baseline to End of Treatment and From End of Treatment to Follow-up
timeFrame: 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)
measure: Change in 24-hour Glucose Excretion From Baseline to Start of Treatment
timeFrame: From baseline (Day -3 to Day -1) to start of treatment (Day 2 to 4)
measure: Change in 24-hour Glucose Excretion From Baseline to End of Treatment
timeFrame: From baseline (Day -3 to Day -1) to end of treatment (Day 12 to 14)
measure: Change in 24-hour Glucose Excretion From End of Treatment to Follow-up
timeFrame: From end of treatment (Day 12 to 14) to follow-up (Day 15 to 17)
measure: Change in Mean 24-hour Systolic Blood Pressure From Baseline to Start of Treatment
timeFrame: From baseline (Day -1) to start of treatment (Day 4)
measure: Change in Mean 24-hour Systolic Blood Pressure From Baseline to End of Treatment
timeFrame: From baseline (Day -1) to end of treatment (Day 13)
measure: Change in Mean 24-hour Systolic Blood Pressure From End of Treatment to End of Follow-up
timeFrame: From end of treatment (Day 13) to end of follow-up (Day 18)
measure: Change in Plasma Volume From Baseline to Start of Treatment
timeFrame: From baseline (Day 1) to start of treatment (Day 4)
measure: Change in Plasma Volume From Baseline to End of Treatment
timeFrame: From baseline (Day 1) to end of treatment (Day 14)
measure: Change in Plasma Volume From End of Treatment to End of Follow-up
timeFrame: From end of treatment (Day 14) to end of follow-up (Day 18)
measure: Change in Extracellular Volume From Baseline to Start of Treatment
timeFrame: From baseline (Day 1) to start of treatment (Day 4)
measure: Change in Extracellular Volume From Baseline to End of Treatment
timeFrame: From baseline (Day 1) to end of treatment (Day 14)
measure: Change in Extracellular Volume From End of Treatment to End of Follow-up
timeFrame: From end of treatment (Day 14) to end of follow-up (Day 18)
measure: Change in 24-hour Urine Albumin:Creatinine Ratio (UACR)
timeFrame: 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)
measure: Pharmacokinetics of Dapagliflozin on Day 4 and Day 14
timeFrame: At pre-dose (Day 4) and at pre-dose, 1h, 2h, 4h post-dose (Day 14)
measure: Number of Patients With AEs and SAEs
timeFrame: From Day 1 until Day 18 (Follow-up)
Other outcomes:
Locations:
city: Almelo
country: Netherlands
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Örebro
country: Sweden
facility: Research Site
Study officials:
References:
citation: Scholtes RA, Muskiet MHA, van Baar MJB, Hesp AC, Greasley PJ, Hammarstedt A, Karlsson C, Hallow KM, Danser AHJ, Heerspink HJL, van Raalte DH. The Adaptive Renal Response for Volume Homeostasis During 2 Weeks of Dapagliflozin Treatment in People With Type 2 Diabetes and Preserved Renal Function on a Sodium-Controlled Diet. Kidney Int Rep. 2022 Mar 4;7(5):1084-1092. doi: 10.1016/j.ekir.2022.02.023. eCollection 2022 May.
citation: Scholtes RA, Muskiet MHA, van Baar MJB, Hesp AC, Greasley PJ, Karlsson C, Hammarstedt A, Arya N, van Raalte DH, Heerspink HJL. Natriuretic Effect of Two Weeks of Dapagliflozin Treatment in Patients With Type 2 Diabetes and Preserved Kidney Function During Standardized Sodium Intake: Results of the DAPASALT Trial. Diabetes Care. 2021 Feb;44(2):440-447. doi: 10.2337/dc20-2604. Epub 2020 Dec 14.