Effects of Dapagliflozin in Non-diabetic Patients With Proteinuria

NCT03190694 | Completed Phase 2 Results

• 2 other identifiers: 20170030012017-001090-16
• Study Type: interventional
• Target: 53
• Locations: 3 countries
• Sites: 7

Brief Summary

This study tests the hypothesis that dapagliflozin lowers proteinuria in patients with non-diabetic chronic kidney disease.

Conditions

Chronic Kidney Diseases; Proteinuria

Keywords

chronic kidney disease; non diabetic

Outcome Measures

Primary Outcomes (1)

• Change in 24-hr Proteinuria With Dapagliflozin for Six Weeks Relative to Placebo in Patients With Non-diabetic Kidney Disease and Proteinuria 500 mg/Day on Stable Angiotensin-converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Treatment.

  bioequivalence

  6 weeks

Secondary Outcomes (10)

• Effect of Dapagliflozin 10 mg/d Compared to Placebo on Glomerular Filtration Rate (GFR) Using Iohexol Clearance

  6 weeks

• Effect of Dapagliflozin 10 mg/d Compared to Placebo on Systolic/Diastolic Blood Pressure

  week 0, 3, 6, 12, 15, 18, 24

• Effect of Dapagliflozin 10 mg/d Compared to Placebo on Body Weight

  week 0, 3, 6, 12, 15, 18, 24

• Effect of Dapagliflozin 10 mg/d Compared to Placebo on 6-keto-Prostaglandin F1 Alpha/Creatinine Ratio

  Baseline, Week 6

• Safety of Dapagliflozin vs. Placebo - the Number of Participatns With Hypoglycemic Events and/or Serious Adverse Events

  week 0-26

Study Arms (2)

Dapagliflozin 10mg Tablet, then Placebo

EXPERIMENTAL

Participants first received Dapagliflozin 10mg tablet for 6 weeks. After a washout period of 6 weeks, they then received Placebo tablet for 6 weeks (matching Dapagliflozin 10mg). Dapagliflozin 10 mg: Green, plain, diamond shaped, film coated tablet (orally) Placebo: Green, plain, diamond shaped, film coated tablet. Does not contain active ingredient

Drug: Dapagliflozin 10mg

Placebo, then Dapagliflozin

PLACEBO COMPARATOR

Participants first received Placebo tablet for 6 weeks. After a washout period of 6 weeks, they then received Dapagliflozin 10mg tablet for 6 weeks (matching Dapagliflozin 10mg). Placebo: Green, plain, diamond shaped, film coated tablet. Does not contain active ingrediënt Dapagliflozin 10 mg: Green, plain, diamond shaped, film coated tablet (orally)

Drug: Dapagliflozin 10mg

Interventions

Dapagliflozin 10mg DRUG

Tablet

Also known as: Placebo Matching Dapagliflozin 10mg

Dapagliflozin 10mg Tablet, then Placebo; Placebo, then Dapagliflozin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤75 years
• Urinary protein excretion \> 500 mg/g and ≤ 3500 mg/g in a 24-hr urine collection eGFR ≥ 25 mL/min/1.73m2
• On a stable dose of an ACEi or ARB for at least 4 weeks prior to randomization
• Willing to sign informed consent
• Women of Child-Bearing Potential (WOCBP):
• WOCBP must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized.
• WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 0 to 72 hours before the first dose of study drug.
• Women must not be breast-feeding.
• WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal.

You may not qualify if:

• Diagnosis of type 1 or type 2 diabetes mellitus
• Urinary protein excretion \> 3500 mg/day
• Peripheral Vascular Disease
• Autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis
• Indication for immunosuppressants as per the treating physician's judgment.
• Receiving cytotoxic therapy, immunosuppressive therapy, or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment.
• Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
• Use of co-interventional treatments (outlined in section 4.2 of the protocol) within 6 weeks of screening will not be allowed.
• Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following:
• History of active inflammatory bowel disease within the last six months;
• Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
• Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
• Pancreatic injury or pancreatitis within the last six months;
• Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at the screening visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt;
• Evidence of urinary obstruction of difficulty in voiding at screening

Sponsors & Collaborators

• Hiddo Lambers Heerspink: lead
• AstraZeneca: collaborator

Study Sites (7)

Nephrology Dept., Vancouver Coastal Health Research Institute

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Division of Nephrology University Health Network, University of Toronto

Toronto, Ontario, M5G 2C4, Canada

Location

Nephrology Unit, University Kebangsaan Malaysia

Kuala Lumpur, 5600, Malaysia

Location

University Malaya Medical Centre, Ward 8TE

Kuala Lumpur, 59100, Malaysia

Location

Dept Internal Medicine, division of Nephrology Hospital Group Twente

Almelo, 7609 PP, Netherlands

Location

Dept.of Nephrology, VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Dept. Nephrology, University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Related Publications (2)

• van der Aart-van der Beek AB, Koomen JV, Dekkers CCJ, Barbour SJ, Boulton DW, Gansevoort RT, Greasley PJ, Abdul Gafor AH, Laverman GD, Li Q, Lim SK, Stevens J, Vervloet MG, Singh S, Cattran DC, Reich HN, Cherney DZI, Heerspink HJL. Evaluation of the Pharmacokinetics and Exposure-Response Relationship of Dapagliflozin in Patients without Diabetes and with Chronic Kidney Disease. Clin Pharmacokinet. 2021 Apr;60(4):517-525. doi: 10.1007/s40262-020-00956-1. Epub 2021 Feb 15.

  PMID: 33587286 DERIVED

• Cherney DZI, Dekkers CCJ, Barbour SJ, Cattran D, Abdul Gafor AH, Greasley PJ, Laverman GD, Lim SK, Di Tanna GL, Reich HN, Vervloet MG, Wong MG, Gansevoort RT, Heerspink HJL; DIAMOND investigators. Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial. Lancet Diabetes Endocrinol. 2020 Jul;8(7):582-593. doi: 10.1016/S2213-8587(20)30162-5.

  PMID: 32559474 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Proteinuria

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Urination Disorders; Urological Manifestations; Signs and Symptoms

Results Point of Contact

• Title: Prof.dr.H.J. Lambers-Heerspink
• Organization: University Medical Center Groningen

h.j.lambers.heerspink@umcg.nl

+31 50 361 7859

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Pharmacologist

Model Details: A Randomized Double Blind 6-Weeks Cross-over

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: June 19, 2017
• Study Start: November 12, 2017
• Primary Completion: November 1, 2019
• Study Completion: December 1, 2019
• Last Updated: June 17, 2024
• Results First Posted: June 17, 2024

Record last verified: 2024-01

Locations

CA (2); MY (2); NL (3)