Effects of Dapagliflozin in Non-diabetic Patients With Proteinuria

• Status: Unknown status
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hiddo Lambers Heerspink
• Collaborator: AstraZeneca
• Treatments: Dapagliflozin

Criteria

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.