A Study to Assess the Effects of Zibotentan and Dapagliflozin in Patients With Type 2 Diabetes and Elevated Albuminuria

• Status: Not yet recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to test the hypothesis that the effects on albuminuria of combination treatment with the endothelin receptor antagonist zibotentan and SGLT2i dapagliflozin are complimentary and additive while the fluid retaining effects of zibotentan can be mitigated by dapagliflozin.

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

Details

• Lead Sponsor: University Medical Center Groningen
• Collaborator: AstraZeneca
• Treatments: Dapagliflozin

Criteria

Inclusion Criteria:

• Age ≥18 and ≤75 years

• Diagnosis of type 2 diabetes

• Hba1c ≥ 6.0%

• Urinary albumin:creatinine ratio > 100 mg/g and ≤ 3500 mg/g in a first morning void urine collection

• eGFR ≥ 30 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

Exclusion Criteria:

• Diagnosis of type 1 diabetes

• Non-diabetic kidney disease considered to be dominant etiology of albuminuria

• Hba1c > 12.5%

• Urinary protein excretion > 3500 mg/day

• Heart Failure NYHA Class III or IV

• NT-proBNP > 600 pg/ml

• Acute coronary syndrome event within the preceding 6 months

• Severe peripheral edema according to investigators opinion

• Women of childbearing potential (WOCBP). WOCBP is defined as 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

• Pregnancy or breastfeeding

• Indication for immunosuppressants as per the treating physician's judgment.

• Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin within the last 5 years.

• Use of the co-interventional treatments (outlined in section 4.2) 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 or difficulty in voiding at screening

• Severe hepatic impairment

• History of epilepsy syndrome

• History of severe hypersensitivity or contraindications to dapagliflozin

• History of hypersensitivity or contraindications to iodinated contrast media

• 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 or according to investigator's assessment.

• 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.