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.

NCT03152084 | Terminated Phase 4 Results

• 2 other identifiers: D1690C000492016-002961-79
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 4

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

Conditions

Diabetes Mellitus, Type 2; Kidney Function Tests

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

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

  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

  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

  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

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

• Change in Mean 24-hour Systolic Blood Pressure From Baseline to Start of Treatment

  From baseline (Day -1) to start of treatment (Day 4)

Study Arms (3)

Arm 1

EXPERIMENTAL

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

Drug: Dapagliflozin

Arm 2

EXPERIMENTAL

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.

Drug: Dapagliflozin

Arm 3

EXPERIMENTAL

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

Drug: Dapagliflozin

Interventions

Dapagliflozin DRUG

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

Arm 1; Arm 2; Arm 3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Almelo, 7609 PP, Netherlands

Location

Research Site

Amsterdam, 1081 HV, Netherlands

Location

Research Site

Örebro, 70185, Sweden

Location

Research Site

Stockholm, 14186, Sweden

Location

Related Publications (2)

• 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.

  PMID: 35570989 DERIVED

• 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.

  PMID: 33318125 DERIVED

Related Links

• Redacted CSP
• Redacted SAP

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

The study was prematurely closed due to unsatisfactory recruitment rate. Of 5 patients enrolled in the Group 1, none were enrolled into the Run-in set due to failure to meet inclusion/exclusion criteria, screen failure, withdrawal or other reason and hence it was decided that no more Group 1 patients would be enrolled in the study. In Group 2 and 3, 17 and 7 patients received the investigational product and completed the study, respectively.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: May 12, 2017
• Study Start: July 12, 2017
• Primary Completion: March 20, 2020
• Study Completion: March 20, 2020
• Last Updated: May 28, 2021
• Results First Posted: May 28, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

SE (2); NL (2)