A Phase 2 interventional study of Zibotentan and Dapagliflozin in Chronic Kidney Diseases, sponsored by University Medical Center Groningen. Completed at 7 sites in 5 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-04-30.
Sponsored by University Medical Center Groningen · Phase 2, Interventional, and Treatment
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.
A double-blind randomized placebo controlled cross-over study will be conducted in male and female subjects with type 2 diabetes aged between 18 and 75 years, urinary albumin:creatinine ratio (UACR) levels between 100 and 3500 mg/g, and an eGFR ≥ 30 ml/min/1.73m2 will be enrolled. Patients with type 1 diabetes or non-diabetic kidney disease will be excluded.
The study will consist of a screening visit, a 4-week (up to a maximum of 16-weeks) run-in phase for those subjects not on stable ACEi/ARB treatment. Subjects will be randomly assigned to one of two treatment orders. Each treatment order consists of three treatment periods, separed separated by 4-week wash-out period. Treatment period 1 and 2 take four weeks. The third treatment period last 6 weeks.
Participants will be randomized to treatments in addition to receiving background local standard of care (SoC) therapy as follows:
3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.
This study's enrollment of 42 is below the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.
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Exclusion Criteria:
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:
Subjects will start with 4 weeks of placebo in treatment period one, then 4 weeks of zibotentan during treatment period two. The order of the first two treatment periods is random which means that patients can start with either placebo or zibotentan. Then in treatment period three, patients are randomized to either either placebo or dapagliflozin for 2 weeks followed immediately by 4 weeks of both zibotentan and dapagliflozin. Between treatment periods there is a 4-week wash-out.
Drug: Zibotentan · Drug: Dapagliflozin · Drug: Placebo · Drug: Dapagliflozin and Zibotentan
Subjects will start with 4 weeks of dapagliflozine in treatment period one, then 4 weeks of zibotentan during treatment period two. The order of the first two treatment periods is random which means that patients can start with either dapagliflozine or zibotentan. Then in treatment period three, patients are randomized to either either placebo or dapagliflozin for 2 weeks followed immediately by 4 weeks of both zibotentan and dapagliflozin. Between treatment periods there is a 4-week wash-out.
Drug: Zibotentan · Drug: Dapagliflozin · Drug: Placebo · Drug: Dapagliflozin and Zibotentan
Zibotentan 1.5 mg once per day as a hard capsule.
Dapagliflozin 10 mg once per day as a tablet.
Matching placebo.
Dapagliflozin 10 mg once per day as a tablet in combination with zibotentan 1.5 mg once per day as a hard capsule.
Change from baseline in albuminuria after 4 weeks combined zibotentan and dapagliflozin treatment versus four weeks treatment with zibotentan alone.
The change in albuminuria as expressed the percentage change of the log-transformed albumin:creatinine ratio in mg/gram. The log-transformation is because of the skewed distribution.
Time frame: The albuminuria will be measured before start of medication intake and after the last intake of medication for each treatment period. This concerns a 4 week time frame.
Change in Extracellular Fluid
Extracellular Fluid measured by bioimpedance spectroscopy
Time frame: 4 weeks
Change in bodyweight
Change in kilograms
Time frame: 4 weeks
Change in NT-proBNP
N-terminal B-type natriuretic peptide (NT-proBNP)
Time frame: 4 weeks
Change in BNP
B-type natriuretic peptide (BNP)
Time frame: 4 weeks
Change in Glomerular Filtration Rate (GFR)
Glomerular Filtration Rate (GFR) using iohexol clearance techniques.
Time frame: 4 weeks
Change in Extracellular volume (ECV)
Extracellular volume (ECV) using iohexol clearance techniques.
Time frame: 4 weeks
Change in hematocrit
The percentage of red blood cells in blood
Time frame: 4 weeks
Change in systolic and diastolic blood pressure
Change in blood pressure as measure in mmHg
Time frame: 4 weeks
Change in renin-angiotensin-aldosterone system (RAAS) markers
Change in RAAS markers in plasma and urine
Time frame: 4 weeks
Change in copeptin
Change in copeptin as a surrogate of vasopressin
Time frame: 4 weeks
Plan to share: Undecided
This study is completed, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.
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University Medical Center Groningen