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Effects of Dapagliflozin in Non-diabetic Patients With Proteinuria (DIAMOND)

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ClinicalTrials.gov Identifier: NCT03190694
Recruitment Status : Recruiting
First Posted : June 19, 2017
Last Update Posted : October 5, 2018
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Hiddo Lambers Heerspink, University Medical Center Groningen

Tracking Information
First Submitted Date  ICMJE June 15, 2017
First Posted Date  ICMJE June 19, 2017
Last Update Posted Date October 5, 2018
Actual Study Start Date  ICMJE November 12, 2017
Estimated Primary Completion Date July 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
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. [ Time Frame: 6 weeks ]
bioequivalence
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03190694 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
  • Effect of dapagliflozin 10 mg/d compared to placebo on Glomerular Filtration Rate (GFR) using iohexol clearance [ Time Frame: 6 weeks ]
    bioequivalence
  • Effect of dapagliflozin 10 mg/d compared to placebo on systolic/diastolic blood pressure [ Time Frame: week 0, 2, 4, 5, 6, 12, 15, 18, 24 ]
    bioequivalence
  • Effect of dapagliflozin 10 mg/d compared to placebo on body weight [ Time Frame: week 0, 2, 4, 5, 6, 12, 15, 18, 24 ]
    bioequivalence
  • Effect of dapagliflozin 10 mg/d compared to placebo on selected neurohormones/ biomarkers [ Time Frame: week 0, 3, 6, 12, 15, 18, 24 ]
    bioequivalence
  • Safety of dapagliflozin vs. placebo - the number of hypoglycemia episodes between groups and serious adverse events [ Time Frame: week 0-26 ]
    safety
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Dapagliflozin in Non-diabetic Patients With Proteinuria
Official Title  ICMJE A Study to Assess the Renoprotective Effects of the SGLT2 Inhibitor Dapagliflozin in Non-Diabetic Patients With Proteinuria: a Randomized Double Blind 6-Weeks Cross-Over Trial
Brief Summary This study tests the hypothesis that dapagliflozin lowers proteinuria in patients with non-diabetic chronic kidney disease.
Detailed Description

Despite optimal treatment with renin-angiotensin-aldosterone-system (RAAS) inhibitors, many patients with non-diabetic kidney disease show progressive kidney function loss, which is associated with high residual proteinuria. Novel treatment strategies are therefore required to further decrease proteinuria and to slow kidney function decline.

Dapagliflozin is a sodium-glucose transport (SGLT2) inhibitor and inhibits the reabsorption of glucose and sodium in the proximal tubule. The increased natriuresis following dapagliflozin administration normalizes tubuloglomerular feedback resulting in a reduction in intra-glomerular hypertension, which is in turn manifested by acute reversible reductions in glomerular filtration rate and albuminuria. Since many etiologies of non-diabetic nephropathy are characterized by intraglomerular hypertension, we hypothesize that dapagliflozin acutely decreases GFR and proteinuria in patients without diabetes at risk of progressive kidney function loss via a glucose independent hemodynamic mechanism.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
A Randomized Double Blind 6-Weeks Cross-over
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Chronic Kidney Diseases
  • Proteinuria
Intervention  ICMJE Drug: Dapagliflozin 10mg
Tablet
Other Name: Placebo Matching Dapagliflozin 10mg
Study Arms  ICMJE
  • Experimental: Dapagliflozin 10mg Tablet
    10 mg Green, plain, diamond shaped, film coated tablet (orally)
    Intervention: Drug: Dapagliflozin 10mg
  • Placebo Comparator: Placebo Matching Dapagliflozin Tablet
    Green, plain, diamond shaped, film coated tablet. Does not contain active ingredient
    Intervention: Drug: Dapagliflozin 10mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 16, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2019
Estimated Primary Completion Date July 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Diagnosis of type 1 or type 2 diabetes mellitus
  • Urinary protein excretion > 3500 mg/day
  • 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.
  • 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
  • History of severe hypersensitivity or contraindications to dapagliflozin
  • Subject who, in the assessment of the investigator, may be at risk for dehydration or volume depletion that may affect the interpretation of efficacy or safety data
  • Participation in any clinical investigation within 3 months prior to initial dosing.
  • Donation or loss of 400 ml or more of blood within 8 weeks prior to initial dosing.
  • History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening.
  • History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
  • Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
  • Pregnancy or breastfeeding
  • WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 4 weeks after the last dose of study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hiddo J Lambers Heerspink, Prof.Dr. +31-50-3617859 h.j.lambers.heerspink@umcg.nl
Contact: David Cherney, Prof.Dr.MD +1-416-340-4151 david.cherney@uhn.ca
Listed Location Countries  ICMJE Canada,   Malaysia,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03190694
Other Study ID Numbers  ICMJE 2017003001
2017-001090-16 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Hiddo Lambers Heerspink, University Medical Center Groningen
Study Sponsor  ICMJE Hiddo Lambers Heerspink
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE Not Provided
PRS Account University Medical Center Groningen
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP