Study to Investigate Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin in Participants With Chronic Kidney Disease and High Proteinuria (ZENITH High Proteinuria)
NCT ID: NCT06087835
Last Updated: 2025-11-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
1835 participants
INTERVENTIONAL
2023-11-07
2027-01-22
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Zibotentan/Dapagliflozin dose A or Zibotentan/Dapagliflozin dose B
Drug dose (dose A or B) are determined based on eGFR values. Participants will receive daily oral dose of zibotentan/dapagliflozin in fixed dose combination.
Zibotentan/Dapagliflozin
Participants will receive zibotentan/dapagliflozin in fixed-dose combination as per the arms they are randomized to
Dapagliflozin alone
Participants will receive daily oral dose of dapagliflozin.
Dapagliflozin
Participants will receive dapagliflozin as per the arms they are randomized to
Interventions
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Zibotentan/Dapagliflozin
Participants will receive zibotentan/dapagliflozin in fixed-dose combination as per the arms they are randomized to
Dapagliflozin
Participants will receive dapagliflozin as per the arms they are randomized to
Eligibility Criteria
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Inclusion Criteria
2. Diagnosis of CKD, defined as eGFR ≥ 20 and \< 90 mL/min/1.73 m2 and UACR \> 700 mg/g (\> 79 mg/mmol) or UPCR \> 1000 mg/g (\> 113 mg/mmoL).
3. All female participants must have a negative serum pregnancy test result at screening.
4. Female participants must be either
* not of child-bearing potential or
* women of child bearing potential (WOCBP) using at least one highly effective birth control method for at least 3 months prior to first dose of study intervention
5. Capable of giving signed informed consent
6. Provision of signed informed consent prior to any study specific procedure.
7. Provision of electronic informed consent prior to completion of the optional Study Participant Feedback Questionnaire (SPFQ).
8. Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics imitative research that supports the Genomic Initiative.
9. 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
2. Participants hospitalised for HF during the last 6 month prior to screening.
3. Evidence of rales or jugular venous distention on physical examination.
4. Participants with type 1 diabetes mellitus.
5. History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal).
6. Blood pressure above 160 mmHg systolic.
7. Blood pressure below 90 mmHg systolic.
8. Participants hospitalised for heart disease or cardiac procedures or for COVID-19 during the last 3 months prior to screening.
9. History of solid organ transplantation or bone marrow transplant.
10. History or ongoing allergy/hypersensitivity, as judged by the Investigator, to SGLT2i therapy (eg, dapagliflozin, canagliflozin, empagliflozin or other SGLT2 inhibitors) or Endothelin Receptor Antagonists (eg, ambrisentan, atrasentan, bosentan, or other).
11. Any condition with a life expectancy of less than 2 years based on investigator´s clinical judgment.
12. Malignancy within the past 5 years. Exceptions to this criterion include non-melanoma skin cancer and curatively treated cervical carcinoma in situ.
13. Significant liver disease as judged by the investigator or severe hepatic impairment with AST or ALT \> 3 × ULN; or total bilirubin \> 2 × ULN at time of screening. An isolated increase in bilirubin in participants with known Gilbert's syndrome is not a reason for exclusion.
14. Known blood-borne diseases.
15. Clinically significant, unstable, or uncontrolled medical condition as assessed by the Investigator.
16. Participants on renal replacement therapy or previous kidney transplant.
17. Known history of drug or alcohol abuse within 12 months of screening.
18. Participants on treatment with strong or moderate CYP3A4 inducer.
19. Participants on systemic immunosuppression therapy other than stable maintenance therapy defined as prednisone 10 mg/day (or equivalent) or less, aziothioprine 100 mg/day or less; MMF 1000 mg/day or less for at least 3 months prior to Visit 1. Inhaled, nasal or dermatological steroids are also allowed.
20. Participants treated or expecting to be treated with tolvaptan, any other ERAs, or budesonide (where used to treat IBD or IgAN).
21. Participation in another clinical study with a study intervention administered in the last 3 months.
18 Years
95 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
Responsible Party
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Locations
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Huntsville, Alabama, United States
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Sun City West, Arizona, United States
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Bakersfield, California, United States
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Huntington Park, California, United States
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Los Alamitos, California, United States
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Los Angeles, California, United States
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Northridge, California, United States
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Oxnard, California, United States
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San Carlos, California, United States
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San Dimas, California, United States
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Tarzana, California, United States
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Victorville, California, United States
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Arvada, Colorado, United States
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Denver, Colorado, United States
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Boynton Beach, Florida, United States
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Hialeah, Florida, United States
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Hollywood, Florida, United States
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Jacksonville, Florida, United States
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Jensen Beach, Florida, United States
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Miami, Florida, United States
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Miami, Florida, United States
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Orlando, Florida, United States
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Fayetteville, Georgia, United States
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Champaign, Illinois, United States
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Chicago, Illinois, United States
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Hinsdale, Illinois, United States
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Island Lake, Illinois, United States
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Skokie, Illinois, United States
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Bowling Green, Kentucky, United States
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Shreveport, Louisiana, United States
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Silver Spring, Maryland, United States
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Flint, Michigan, United States
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Flint, Michigan, United States
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Troy, Michigan, United States
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City of Saint Peters, Missouri, United States
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Albany, New York, United States
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Middletown, New York, United States
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Orchard Park, New York, United States
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Greenville, North Carolina, United States
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Jacksonville, North Carolina, United States
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Kinston, North Carolina, United States
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New Bern, North Carolina, United States
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Statesville, North Carolina, United States
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Wilmington, North Carolina, United States
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Wilmington, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Maumee, Ohio, United States
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Pottstown, Pennsylvania, United States
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East Providence, Rhode Island, United States
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Kingsport, Tennessee, United States
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Arlington, Texas, United States
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Austin, Texas, United States
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Houston, Texas, United States
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Houston, Texas, United States
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Pearland, Texas, United States
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San Antonio, Texas, United States
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San Antonio, Texas, United States
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San Antonio, Texas, United States
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Sugar Land, Texas, United States
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Salt Lake City, Utah, United States
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Alexandria, Virginia, United States
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Newport News, Virginia, United States
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Mukilteo, Washington, United States
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Spokane, Washington, United States
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Ciudad de Buenos Aires, , Argentina
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Ciudad de Buenos Aires, , Argentina
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Mar del Plata, , Argentina
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Mar del Plata, , Argentina
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Santa Fe, , Argentina
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Gosford, , Australia
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Meadowbrook, , Australia
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Perth, , Australia
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Reservoir, , Australia
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Reservoir, , Australia
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Southport, , Australia
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Feldkirch, , Austria
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Vienna, , Austria
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Belém, , Brazil
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Botucatu, , Brazil
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Joinville, , Brazil
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São José do Rio Preto, , Brazil
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São Paulo, , Brazil
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São Paulo, , Brazil
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São Paulo, , Brazil
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Dobrich, , Bulgaria
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Pleven, , Bulgaria
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Plovdiv, , Bulgaria
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Plovdiv, , Bulgaria
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Sofia, , Bulgaria
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Stara Zagora, , Bulgaria
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London, Ontario, Canada
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Waterloo, Ontario, Canada
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Greenfield Park, Quebec, Canada
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Montreal, Quebec, Canada
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Baotou, , China
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Beijing, , China
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Beijing, , China
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Changsha, , China
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Chengdu, , China
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Chengdu, , China
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Chongqing, , China
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Deyang, , China
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Foshan, , China
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Guangzhou, , China
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Guangzhou, , China
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Hangzhou, , China
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Hengyang, , China
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Linhai, , China
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Nanjing, , China
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Nanjing, , China
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Nanning, , China
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Ningbo, , China
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Pingxiang, , China
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Shanghai, , China
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Shantou, , China
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Shenzhen, , China
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Shenzhen, , China
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Wenzhou, , China
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Wuhan, , China
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Wuxi, , China
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Xi'an, , China
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Xiamen, , China
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Yantai, , China
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Yibin, , China
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Yinchuan, , China
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Zhuzhou, , China
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Zigong, , China
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Aalborg, , Denmark
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Aarhus, , Denmark
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Herlev, , Denmark
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Herning, , Denmark
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Roskilde, , Denmark
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La Tronche, , France
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Mulhouse, , France
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Nice, , France
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Nîmes, , France
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Rouen, , France
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Saint-Priest-en-Jarez, , France
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Strasbourg, , France
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Tours, , France
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Aachen, , Germany
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Bad Oeynhausen, , Germany
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Berlin, , Germany
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Dresden, , Germany
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Hanover, , Germany
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Mainz, , Germany
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München, , Germany
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Bangalore, , India
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Belagavi, , India
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Delhi, , India
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Nadiād, , India
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New Delhi, , India
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Ashkelon, , Israel
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Haifa, , Israel
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Jerusalem, , Israel
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Kfar Saba, , Israel
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Nahariya, , Israel
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Petah Tikva, , Israel
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Ramat Gan, , Israel
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Rehovot, , Israel
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Bergamo, , Italy
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Bologna, , Italy
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Foggia, , Italy
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Genoa, , Italy
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Napoli, , Italy
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Pisa, , Italy
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Roma, , Italy
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Torino, , Italy
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Chūōku, , Japan
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Fujisawa-shi, , Japan
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Fukui-shi, , Japan
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Fukuoka, , Japan
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Fukuoka, , Japan
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Fukuoka, , Japan
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Hashima-gun, , Japan
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Kamakura-shi, , Japan
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Kasuga-shi, , Japan
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Kawaguchi-shi, , Japan
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Kitakyushu-shi, , Japan
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Kitakyusyu-shi, , Japan
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Kofu, , Japan
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Kurume-shi, , Japan
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Kurume-shi, , Japan
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Kusatsu-shi, , Japan
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Kyoto, , Japan
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Matsumoto-shi, , Japan
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Meguro-ku, , Japan
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Minatoku, , Japan
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Minokamo Shi, , Japan
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Nishinomiya-Shi, , Japan
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Nishinomiya-shi, , Japan
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Okawa-shi, , Japan
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Osaka, , Japan
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Osaka, , Japan
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Oyama-shi, , Japan
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Sakushu, , Japan
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Sapporo, , Japan
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Sapporo, , Japan
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Sendai, , Japan
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Soka-shi, , Japan
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Takamatsu, , Japan
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Takasago-shi, , Japan
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Tondabayashi-shi, , Japan
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Toride-shi, , Japan
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Urayasu, , Japan
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Utsunomiya, , Japan
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Alor Star, , Malaysia
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Ipoh, , Malaysia
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Kota Kinabalu, , Malaysia
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Kuala Lumpur, , Malaysia
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Seremban, , Malaysia
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Seri Manjung, , Malaysia
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Mazatlán, , Mexico
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Amersfoort, , Netherlands
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Breda, , Netherlands
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Dordrecht, , Netherlands
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Bodø, , Norway
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Lørenskog, , Norway
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Oslo, , Norway
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Stavanger, , Norway
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Tromsø, , Norway
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Chrzanów, , Poland
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Krakow, , Poland
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Krakow, , Poland
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Lodz, , Poland
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Poznan, , Poland
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Radom, , Poland
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Rzeszów, , Poland
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Szczecin, , Poland
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Warsaw, , Poland
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Lučenec, , Slovakia
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Prešov, , Slovakia
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Púchov, , Slovakia
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Rožňava, , Slovakia
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Trebišov, , Slovakia
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Benoni, , South Africa
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Cape Town, , South Africa
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Chatsworth, , South Africa
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Durban, , South Africa
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Lenasia, , South Africa
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Midrand, , South Africa
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Parow, , South Africa
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Ansan-si, , South Korea
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Busan, , South Korea
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Cheonan-si, , South Korea
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Daegu, , South Korea
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Goyang-si, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Girona, , Spain
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L'Hospitalet de Llobregat, , Spain
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Lugo, , Spain
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Madrid, , Spain
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Majadahonda, , Spain
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Seville, , Spain
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Valencia, , Spain
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Gothenburg, , Sweden
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Linköping, , Sweden
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Rättvik, , Sweden
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Stockholm, , Sweden
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Uppsala, , Sweden
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Kaohsiung City, , Taiwan
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Kaohsiung City, , Taiwan
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New Taipei City, , Taiwan
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Taichung, , Taiwan
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Tainan City, , Taiwan
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Taipei, , Taiwan
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Taipei, , Taiwan
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Taipei, , Taiwan
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Taoyuan District, , Taiwan
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Bangkok, , Thailand
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Bangkok, , Thailand
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Chaingmai, , Thailand
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Hat Yai, , Thailand
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Khon Kaen, , Thailand
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Ratchathewi, , Thailand
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Adapazarı, , Turkey (Türkiye)
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Ankara, , Turkey (Türkiye)
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Bursa, , Turkey (Türkiye)
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Dinar, , Turkey (Türkiye)
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Kahramanmaraş, , Turkey (Türkiye)
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Kayseri, , Turkey (Türkiye)
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Kocaeli, , Turkey (Türkiye)
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Cardiff, , United Kingdom
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Dundee, , United Kingdom
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Glasgow, , United Kingdom
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London, , United Kingdom
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London, , United Kingdom
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London, , United Kingdom
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York, , United Kingdom
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Haiphong, , Vietnam
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Hanoi, , Vietnam
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Ho Chi Minh City, , Vietnam
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Ho Chi Minh City, , Vietnam
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Ho Chi Minh City, , Vietnam
Countries
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References
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Smeijer JD, Wasehuus VS, Dhaun N, Gorriz JL, Soler MJ, Astrand M, Mercier AK, Greasley PJ, Ambery P, Heerspink HJL. Effects of Zibotentan Alone and in Combination with Dapagliflozin on Fluid Retention in Patients with CKD. J Am Soc Nephrol. 2024 Oct 1;35(10):1381-1390. doi: 10.1681/ASN.0000000000000436. Epub 2024 Jul 12.
Other Identifiers
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2023-504124-26
Identifier Type: REGISTRY
Identifier Source: secondary_id
D4325C00010
Identifier Type: -
Identifier Source: org_study_id