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)
Launched by ASTRAZENECA · Oct 17, 2023
Trial Information
Current as of May 07, 2025
Active, not recruiting
Keywords
ClinConnect Summary
The ZENITH High Proteinuria study is looking at two treatments for people with chronic kidney disease (CKD) who have high levels of protein in their urine, a condition known as high proteinuria. Specifically, the trial will compare the effects of a combination medication called zibotentan/dapagliflozin to dapagliflozin alone. This research aims to find out which treatment is more effective and to assess their safety and how well patients tolerate them.
To participate, you need to be 18 years or older with a diagnosis of CKD that meets certain criteria. You should also be stable on specific heart medications for at least four weeks. If you join the study, you will receive either of the treatments and be monitored closely for any side effects or changes in your condition. It's important to note that certain health issues or recent hospitalizations may exclude you from participating, so it's best to discuss with your doctor if you're interested. This trial is actively recruiting participants, and your involvement could help improve treatment options for CKD in the future.
Gender
ALL
Eligibility criteria
- Inclusion Criteria:
- • 1. Participant must be ≥ 18 years of age and of legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.
- • 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:
- • 1. Participants with NYHA class III or class IV Congestive HF at the time of enrolment.
- • 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.
About Astrazeneca
AstraZeneca is a global biopharmaceutical company dedicated to the discovery, development, and commercialization of innovative medicines across various therapeutic areas, including oncology, cardiovascular, respiratory, and autoimmune diseases. With a strong commitment to scientific research and patient-centric solutions, AstraZeneca leverages cutting-edge technology and a robust pipeline to address unmet medical needs. The company collaborates with healthcare professionals, academic institutions, and other organizations to advance clinical trials and deliver transformative therapies, aiming to improve health outcomes and enhance the quality of life for patients worldwide.
Contacts
Jennifer Cobb
Immunology at National Institute of Allergy and Infectious Diseases (NIAID)
Locations
Arvada, Colorado, United States
Orlando, Florida, United States
Skokie, Illinois, United States
Waterbury, Connecticut, United States
Berlin, , Germany
Huntsville, Alabama, United States
Bakersfield, California, United States
Los Alamitos, California, United States
Madrid, , Spain
Krakow, , Poland
Plovdiv, , Bulgaria
Dundee, , United Kingdom
Torino, , Italy
Wien, , Austria
Greenfield Park, Quebec, Canada
Hannover, , Germany
Breda, , Netherlands
Lublin, , Poland
Stockholm, , Sweden
Rehovot, , Israel
Chicago, Illinois, United States
Hinsdale, Illinois, United States
New Bern, North Carolina, United States
Winston Salem, North Carolina, United States
Houston, Texas, United States
Pleven, , Bulgaria
London, Ontario, Canada
Herlev, , Denmark
Hvidovre, , Denmark
Roskilde, , Denmark
Berlin, , Germany
Mainz, , Germany
Lucenec, , Slovakia
Presov, , Slovakia
Uppsala, , Sweden
Glasgow, , United Kingdom
Denver, Colorado, United States
Boynton Beach, Florida, United States
Shreveport, Louisiana, United States
Little Rock, Arkansas, United States
Botucatu, , Brazil
Foggia, , Italy
Lørenskog, , Norway
Girona, , Spain
Köln, , Germany
San Carlos, California, United States
Troy, Michigan, United States
Wilmington, North Carolina, United States
Kingsport, Tennessee, United States
Ramat Gan, , Israel
Szczecin, , Poland
Greenville, North Carolina, United States
Spokane, Washington, United States
Montreal, Quebec, Canada
Manila, , Philippines
Kaohsiung, , Taiwan
Taichung, , Taiwan
Valencia, , Spain
Perth, , Australia
Nahariya, , Israel
Hollywood, Florida, United States
Newport News, Virginia, United States
New Delhi, , India
Ashkelon, , Israel
Cape Town, , South Africa
Sevilla, , Spain
Chicago, Illinois, United States
Beijing, , China
München, , Germany
Quezon City, , Philippines
Tainan, , Taiwan
Miami, Florida, United States
Stara Zagora, , Bulgaria
Mexico, , Mexico
Bologna, , Italy
Sevilla, , Spain
Aachen, , Germany
Nice, , France
Jacksonville, Florida, United States
Majadahonda, , Spain
Linköping, , Sweden
Victorville, California, United States
Albany, New York, United States
Iloilo City, , Philippines
Taipei, , Taiwan
Bangkok, , Thailand
Herning, , Denmark
Dordrecht, , Netherlands
Victorville, California, United States
Smithtown, New York, United States
Statesville, North Carolina, United States
Buenos Aires, , Argentina
Chongqing, , China
Guangzhou, , China
Yinchuan, , China
Bad Oeynhausen, , Germany
Busan, , Korea, Republic Of
Alor Setar, , Malaysia
Kuala Lumpur, , Malaysia
Amersfoort, , Netherlands
Lublin, , Poland
Roznava, , Slovakia
Lenasia, , South Africa
Soweto, , South Africa
Hialeah, Florida, United States
Stavanger, , Norway
L'hospitalet De Llobregat, , Spain
Ipoh, , Malaysia
Tarzana, California, United States
East Providence, Rhode Island, United States
Pisa, , Italy
Sendai Shi, , Japan
Monterrey, , Mexico
Northridge, California, United States
San Dimas, California, United States
Flint, Michigan, United States
Pontiac, Michigan, United States
Saint Peters, Missouri, United States
Orchard Park, New York, United States
Kinston, North Carolina, United States
Arlington, Texas, United States
Houston, Texas, United States
Oslo, , Norway
Rouen, , France
Bergamo, , Italy
Genoa, , Italy
Huntington Park, California, United States
Mar Del Plata, , Argentina
Kasuga Shi, , Japan
Seoul, , Korea, Republic Of
Veracruz, , Mexico
Pasig City, , Philippines
Chrzanów, , Poland
Kraków, , Poland
Trebišov, , Slovakia
Rättvik, , Sweden
Ratchathewi, , Thailand
Ho Chi Minh City, , Vietnam
Changsha, , China
La Tronche, , France
Fukuoka Shi, , Japan
Hamada Shi, , Japan
Kyoto Shi, , Japan
Bursa, , Turkey
Ho Chi Minh, , Vietnam
Düsseldorf, , Germany
Kocaeli, , Turkey
Kfar Saba, , Israel
Fulda, , Germany
Gosford, , Australia
Linkoping, , Sweden
Nanjing, , China
Ankara, , Turkey
Taoyuan, , Taiwan
Bowling Green, Kentucky, United States
Kamakura Shi, , Japan
Hollywood, Florida, United States
Miami, Florida, United States
Maumee, Ohio, United States
Pittsburgh, Pennsylvania, United States
Everett, Washington, United States
Gerona, , Spain
Waterloo, Ontario, Canada
Pingxiang, , China
Viterbo, , Italy
Chuo Ku, , Japan
Fujisawa Shi, , Japan
Fukui Shi, , Japan
Kurume Shi, , Japan
Daegu, , Korea, Republic Of
Rzeszów, , Poland
Uppsala, , Sweden
Hat Yai, , Thailand
Antalya, , Turkey
Warszawa, , Poland
Kayseri, , Turkey
Gentofte, , Denmark
Cardiff, , United Kingdom
Fort Worth, Texas, United States
Beijing, , China
Guangzhou, , China
Sapporo Shi, , Japan
Napoli, , Italy
Taipei City, , Taiwan
Hanoi, , Vietnam
Palo Alto, California, United States
Feldkirch, , Austria
Shanghai, , China
Hai Phong, , Vietnam
Jerusalem, , Israel
Khon Kaen, , Thailand
Ha Noi, , Vietnam
Jacksonville, North Carolina, United States
Salt Lake City, Utah, United States
Ansan Si, , Korea, Republic Of
Goyang Si, , Korea, Republic Of
New Taipei, , Taiwan
Nadiad, , India
łódź, , Poland
Haifa, , Israel
Dobrich, , Bulgaria
Tours, , France
Nimes, , France
Kosice, , Slovakia
Pearland, Texas, United States
Parow, , South Africa
Aarhus, , Denmark
Lugo, , Spain
Katowice, , Poland
Wenzhou, , China
Kurume Shi, , Japan
Oyama Shi, , Japan
Takamatsu Shi, , Japan
Atlanta, Georgia, United States
Puchov, , Slovakia
Yantai, , China
Aalborg, , Denmark
Hangzhou, , China
Ningbo, , China
Benoni, , South Africa
Strasbourg, , France
São Paulo, , Brazil
Hamden, Connecticut, United States
Sofia, , Bulgaria
Austin, Texas, United States
Toride Shi, , Japan
Missouri City, Texas, United States
Wuhan, , China
Hengyang, , China
Shenzhen, , China
Baotou, , China
Belagavi, , India
Kitakyusyu Shi, , Japan
Kusatsu Shi, , Japan
Joinville, , Brazil
Foshan, , China
Mazatlán, , Mexico
Mazatlán, , Mexico
Saltillo, , Mexico
Shantou, , China
Seremban, , Malaysia
Seri Manjung, , Malaysia
Chengdu, , China
Fayetteville, Georgia, United States
Durban, , South Africa
Rosario, , Argentina
Zhuzhou, , China
Jaipur, , India
Takasago Shi, , Japan
Utsunomiya Shi, , Japan
Ciudad De Buenos Aires, , Argentina
Radom, , Poland
Shenzhen, , China
Cheonan Si, , Korea, Republic Of
Göteborg, , Sweden
Sao Jose Do Rio Preto, , Brazil
Meguro Ku, , Japan
Nishinomiya Shi, , Japan
San Antonio, Texas, United States
Belem, , Brazil
Waterloo, Ontario, Canada
S. Gate, California, United States
Chaingmai, , Thailand
Champaign, Illinois, United States
Kitakyushu Shi, , Japan
Alexandria, Virginia, United States
Kaohsiung City, , Taiwan
Santa Fe, , Argentina
Angeles City, , Philippines
Delhi, , India
Xi 'An, , China
Geilenkirchen, , Germany
Meadowbrook, , Australia
Urayasu, , Japan
Kofu Shi, , Japan
Dinar, , Turkey
Deyang, , China
Roma, , Italy
Adapazarı, , Turkey
Los Angeles, California, United States
Chatsworth, California, United States
Kota Kinabalu, , Malaysia
Sun City West, Arizona, United States
Petah Tikva, , Israel
Bodø, , Norway
Reservoir, , Australia
Southport, , Australia
Linhai, , China
Köln, , Germany
Cuautitlán, , Mexico
Cuernavaca, Mor, , Mexico
Tromsø, , Norway
Chatsworth, , South Africa
Midrand, , South Africa
Yong Kang City, , Taiwan
Wuxi, , China
Yibin, , China
Zigong, , China
Mulhouse, , France
Davao Del Sur, , Philippines
London, , United Kingdom
York, , United Kingdom
Xiamen, , China
St Etienne, , France
Dhanvantari Nagar, , India
Fukuoka Shi, , Japan
Kawaguchi Shi, , Japan
Minato Ku, , Japan
Okawa Shi, , Japan
Cainta, , Philippines
Kahramanmaras, , Turkey
Middletown, New York, United States
Nanning, , China
St Priest En Jarez, , France
Hashima Gun, , Japan
Matsumoto Shi, , Japan
Miyazaki, , Japan
Osaka Shi, , Japan
Saku Shi, , Japan
Sanuki Shi, , Japan
Soka Shi, , Japan
Tondabayashi Shi, , Japan
Poznań, , Poland
Linköping, , Sweden
Minokamo Shi, , Japan
Irondale, Alabama, United States
Island Lake, Illinois, United States
Bartlett, Tennessee, United States
Oxnard, California, United States
Redwood City, California, United States
Jensen Beach, Florida, United States
Atlanta, Georgia, United States
Silver Spring, Maryland, United States
Pottstown, Pennsylvania, United States
North Little Rock, Arkansas, United States
Fort Worth, Texas, United States
Pottstown, Pennsylvania, United States
Dresden, , Germany
Bangalore, , India
Mukilteo, Washington, United States
Minokamo Shi, , Japan
Patients applied
Timeline
First submit
Trial launched
Trial updated
Estimated completion
Not reported