A Study to Assess the Effects of the drugs Zibotentan and Dapagliflozin in Patients with Elevated Levels of Protein in Urine

Phase 1

• Conditions: Patients with elevated Albuminuria; MedDRA version: 21.1Level: PTClassification code 10061835Term: Diabetic nephropathySystem Organ Class: 10038359 - Renal and urinary disorders; MedDRA version: 20.0Level: PTClassification code 10016807Term: Fluid retentionSystem Organ Class: 10027433 - Metabolism and nutrition disorders; MedDRA version: 20.0Level: PTClassification code 10001580Term: AlbuminuriaSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2021-001324-18-NL
• Lead Sponsor: niversity Medical Center Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-15
• Last Update Posted: 11 September 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

Age =18 and =75 years
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

. Diagnosis of type 1 diabetes
. Minimal change disease, unstable rapidly progressing renal disease, and/or renal disease requiring significant immunosuppression, autosomal dominant or autosomal recessive polycystic kidney disease
. Hba1c > 12.5%
. Urinary albumin excretion > 3500 mg/day
. Heart Failure NYHA Class III or IV
. NT-proBNP > 600 pg/ml
. Hemoglobin < 9 g/dL
. 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 high dose immunosuppressants according to Investigators opinion
. 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 within 6 weeks of screening.
. 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:
o History of active inflammatory bowel disease within the last six months;
o Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
o Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
o Pancreatic injury or pancreatitis within the last six months;
o 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;
o Evidence of urinary obstruction or difficulty in voiding at screening
o Severe hepatic impairment
o History of epilepsy syndrome
o History of severe hypersensitivity or contraindications to dapagliflozin
o 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 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 subject at higher risk from his/her participation in the study, or is likely to prevent the subject from complying with the requirements of the study or completing the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified