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Investigating the effects of a combination treatment for chronic kidney disease

A Multicentre, Randomised, Double-blind, Active-Controlled, 2-arm Parallel-group Treatment, Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin Alone in Adult Participants With Chronic Kidney Disease and High Proteinuria

PHASE2 · AstraZeneca · NCT06942910

This study is testing if a new combination of two medications can help adults with chronic kidney disease and high protein levels in their urine feel better compared to just one of the medications.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment224 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca (industry)
Locations15 sites (Aramil and 14 other locations)
Trial IDNCT06942910 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial evaluates the efficacy, safety, and tolerability of a combination of zibotentan and dapagliflozin compared to dapagliflozin alone in adults with chronic kidney disease (CKD) and high proteinuria. Participants will undergo a 28-day run-in period with dapagliflozin before entering a 12-week double-blind phase. The study aims to gather clinical data that could support the approval of this combination treatment in the Eurasian Economic Union. The trial is conducted across multiple centers in Russia.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with chronic kidney disease, high proteinuria, and stable RAASi therapy.

Not a fit: Patients with unstable medical conditions or known hypersensitivity to the study medications may not benefit from this trial.

Why it matters

Potential benefit: If successful, this treatment could significantly improve kidney function and reduce proteinuria in patients with chronic kidney disease.

How similar studies have performed: Other studies have shown promise with similar combination therapies, but this specific approach is novel in the Russian context.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* ≥ 18 years of age at the time of signing the informed consent.
* Diagnosis of CKD with eGFR ≥ 20 and \< 90 mL/min/1.73m2 AND UACR \> 700 mg/g (\> 79 mg/mmol) or UPCR \> 1000 mg/g (\> 113 mg/mmol).
* Body mass index (BMI) within the range ≤40 kg/m2.
* Female participants must be either - not of child-bearing potential or - women of childbearing potential (WOCBP) using at least one highly effective birth control method for at least 3 months prior to first dose of study intervention.
* All WOCBP must have a negative serum pregnancy test result at screening.
* Receiving RAASi therapy (ACEi or ARB), and for the patient maximum tolerated labelled daily dose, that has been stable for at least 4 weeks.

Exclusion Criteria:

* Clinically significant, unstable, or uncontrolled medical condition which in the Investigator's opinion makes it undesirable for the participant to participate in the study.
* Known hypersensitivity to dapagliflozin or zibotentan or any of the excipients of the investigational product. History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2i therapy or ERAs.
* NYHA class III or class IV HF.
* Participants hospitalised for HF and/or who have not been stable on HF therapy during the last 6 months prior to screening.
* HF due to cardiomyopathies that would primarily require other specific treatment.
* High output HF (eg, due to hyperthyroidism or Paget's disease).
* HF due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement.
* Evidence of rales or jugular venous distention on physical examination.
* Type 1 diabetes mellitus.
* History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal).
* Participants hospitalised for heart disease or cardiac procedures or for COVID-19 during the last 3 months prior to screening.
* History of solid organ transplantation or bone marrow transplant.
* Any condition with a life expectancy of less than 1 year based on investigator´s clinical judgment.
* Malignancy within the past 5 years. Exceptions to this criterion include non-melanoma skin cancer and curatively treated cervical carcinoma in situ.
* Significant liver disease as judged by the investigator.
* Renal replacement therapy or previous kidney transplant.
* Known history of significant drug or alcohol abuse within 12 months of screening.
* On treatment with strong or moderate CYP3A4 inducer.
* On systemic immunosuppression therapy other than prespecified stable maintenance therapy.
* Participants treated or expecting to be treated with tolvaptan (including as part of participation in a clinical trial), any other ERAs, or budesonide (where used to treat IBD or IgAN).
* Systolic blood pressure above 160 mmHg and/or below 90 mmHg.
* Significant impairment of liver function defined as AST or ALT \>3 x upper limit of normal (ULN) or Total serum bilirubin \>2 x ULN (an isolated increase in bilirubin in participants with known Gilbert's syndrome is not a reason for exclusion).
* NT-proBNP ≥ 600 pg/mL (or NT-proBNP ≥ 1200 pg/mL, if associated with atrial fibrillation) measured by local laboratory at screening.
* Any of the following results of echocardiography at screening:

  * left ventricular ejection fraction (LVEF) \< 50%
  * significant ventricular wall motion abnormality or severe cardiac valve abnormalities
  * isolated pulmonary arterial hypertension (as defined by local clinical practice) or right ventricular failure; in the absence of left-sided HF
* Women who are pregnant, breast-feeding, or women with intent of getting pregnant.
* Women who are not willing to use adequate contraception or cannot, in the opinion of the Investigator, understand and/or comply with the study requirements regarding contraception.

Where this trial is running

Aramil and 14 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Chronic Kidney Disease With High Proteinuria, Zibotentan, Nephrology, Dapagliflozin, Sodium-glucose co-transporter 2, sodium-glucose co-transporter 2 inhibitor, Kidney diseases, Endothelin antagonist

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.