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)
A Phase III, Randomised, Multicentre, Double-blind Study to Evaluate the Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin Alone in Participants With Chronic Kidney Disease and High Proteinuria
2 other identifiers
interventional
1,835
29 countries
290
Brief Summary
This is a Phase III, randomised, multicentre, double-blinded study to evaluate efficacy, safety and tolerability of treatment with zibotentan/dapagliflozin and dapagliflozin alone in participants with chronic kidney disease (CKD) and high proteinuria
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2023
Typical duration for phase_3
290 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 4, 2023
CompletedFirst Posted
Study publicly available on registry
October 18, 2023
CompletedStudy Start
First participant enrolled
November 7, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 18, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 18, 2027
March 25, 2026
March 1, 2026
3.3 years
October 4, 2023
March 24, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in eGFR from baseline
To determine whether zibotentan and dapagliflozin in fixed dose combination is superior to dapagliflozin alone to slow decline in kidney function
At month 24
Secondary Outcomes (3)
Change in Urine Albumin to Creatinine Ratio (UACR) from baseline to each participant's mean level
at Month 9
Time to the first occurrence of any of the components of the renal composite endpoint of 40% sustained decline in eGFR or ESKD or renal death
Through study completion, approximately 38 months
Change in Urine Protein to Creatinine Ratio (UPCR) from baseline to each participant's mean level
at Month 9
Study Arms (2)
Zibotentan/Dapagliflozin dose A or Zibotentan/Dapagliflozin dose B
EXPERIMENTALDrug dose (dose A or B) are determined based on eGFR values. Participants will receive daily oral dose of zibotentan/dapagliflozin in fixed dose combination.
Dapagliflozin alone
ACTIVE COMPARATORParticipants will receive daily oral dose of dapagliflozin.
Interventions
Participants will receive zibotentan/dapagliflozin in fixed-dose combination as per the arms they are randomized to
Participants will receive dapagliflozin as per the arms they are randomized to
Eligibility Criteria
You may qualify if:
- 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.
- 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).
- All female participants must have a negative serum pregnancy test result at screening.
- 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
- Capable of giving signed informed consent
- Provision of signed informed consent prior to any study specific procedure.
- Provision of electronic informed consent prior to completion of the optional Study Participant Feedback Questionnaire (SPFQ).
- 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.
- Receiving RAASi therapy (ACEi or ARB), and for the patient maximum tolerated labelled daily dose, that has been stable for at least 4 weeks.
You may not qualify if:
- Participants with NYHA class III or class IV Congestive HF at the time of enrolment.
- Participants hospitalised for HF during the last 6 month prior to screening.
- Evidence of rales or jugular venous distention on physical examination.
- Participants with type 1 diabetes mellitus.
- History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal).
- Blood pressure above 160 mmHg systolic.
- Blood pressure below 90 mmHg systolic.
- 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.
- 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).
- Any condition with a life expectancy of less than 2 years 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.
- Known blood-borne diseases.
- Clinically significant, unstable, or uncontrolled medical condition as assessed by the Investigator.
- Participants on renal replacement therapy or previous kidney transplant.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (296)
Research Site
Huntsville, Alabama, 35805, United States
Research Site
Sun City West, Arizona, 85375, United States
Research Site
Bakersfield, California, 93309, United States
Research Site
Huntington Park, California, 90255, United States
Research Site
Los Alamitos, California, 90720, United States
Research Site
Los Angeles, California, 90010, United States
Research Site
Northridge, California, 91324, United States
Research Site
Oxnard, California, 93036, United States
Research Site
San Carlos, California, 94070, United States
Research Site
San Dimas, California, 91773, United States
Research Site
Tarzana, California, 91356, United States
Research Site
Victorville, California, 92392, United States
Research Site
Arvada, Colorado, 80002, United States
Research Site
Denver, Colorado, 80230, United States
Research Site
Boynton Beach, Florida, 33435, United States
Research Site
Hialeah, Florida, 33016, United States
Research Site
Hollywood, Florida, 33024, United States
Research Site
Jacksonville, Florida, 32204, United States
Research Site
Jensen Beach, Florida, 34957, United States
Research Site
Miami, Florida, 33126, United States
Research Site
Miami, Florida, 33165, United States
Research Site
Orlando, Florida, 32806, United States
Research Site
Fayetteville, Georgia, 30214, United States
Research Site
Champaign, Illinois, 61822, United States
Research Site
Chicago, Illinois, 60616, United States
Research Site
Hinsdale, Illinois, 60521, United States
Research Site
Island Lake, Illinois, 60042, United States
Research Site
Skokie, Illinois, 60077, United States
Research Site
Bowling Green, Kentucky, 42101, United States
Research Site
Shreveport, Louisiana, 71101, United States
Research Site
Silver Spring, Maryland, 20901, United States
Research Site
Flint, Michigan, 48504, United States
Research Site
Flint, Michigan, 48532, United States
Research Site
Troy, Michigan, 48098, United States
Research Site
City of Saint Peters, Missouri, 63376, United States
Research Site
Albany, New York, 12205, United States
Research Site
Middletown, New York, 10940, United States
Research Site
Orchard Park, New York, 14127, United States
Research Site
Greenville, North Carolina, 27834, United States
Research Site
Jacksonville, North Carolina, 28546, United States
Research Site
Kinston, North Carolina, 28504, United States
Research Site
New Bern, North Carolina, 28562, United States
Research Site
Statesville, North Carolina, 28625, United States
Research Site
Wilmington, North Carolina, 28401, United States
Research Site
Wilmington, North Carolina, 28412, United States
Research Site
Winston-Salem, North Carolina, 27103, United States
Research Site
Maumee, Ohio, 43537, United States
Research Site
Pottstown, Pennsylvania, 19464, United States
Research Site
East Providence, Rhode Island, 02915, United States
Research Site
Kingsport, Tennessee, 37660, United States
Research Site
Arlington, Texas, 76015, United States
Research Site
Austin, Texas, 78726, United States
Research Site
Houston, Texas, 77004, United States
Research Site
Houston, Texas, 77099, United States
Research Site
Pearland, Texas, 77584, United States
Research Site
San Antonio, Texas, 78204, United States
Research Site
San Antonio, Texas, 78207, United States
Research Site
San Antonio, Texas, 78212, United States
Research Site
Sugar Land, Texas, 77478, United States
Research Site
Salt Lake City, Utah, 84115, United States
Research Site
Alexandria, Virginia, 22311, United States
Research Site
Newport News, Virginia, 23606, United States
Research Site
Mukilteo, Washington, 98275, United States
Research Site
Spokane, Washington, 99202, United States
Research Site
Ciudad de Buenos Aires, 1280, Argentina
Research Site
Ciudad de Buenos Aires, C1425AGC, Argentina
Research Site
Mar del Plata, 7600, Argentina
Research Site
Mar del Plata, B7600, Argentina
Research Site
Santa Fe, S3000, Argentina
Research Site
Gosford, 2250, Australia
Research Site
Meadowbrook, 4131, Australia
Research Site
Perth, 6000, Australia
Research Site
Reservoir, 3021, Australia
Research Site
Reservoir, 3073, Australia
Research Site
Southport, 4222, Australia
Research Site
Feldkirch, 6800, Austria
Research Site
Vienna, 1130, Austria
Research Site
Belém, 66073-005, Brazil
Research Site
Botucatu, 18618-687, Brazil
Research Site
Joinville, 89227-680, Brazil
Research Site
São José do Rio Preto, 15090-000, Brazil
Research Site
São Paulo, 01228-200, Brazil
Research Site
São Paulo, 04012-909, Brazil
Research Site
São Paulo, 04038-031, Brazil
Research Site
Dobrich, 9300, Bulgaria
Research Site
Pleven, 5800, Bulgaria
Research Site
Plovdiv, 4000, Bulgaria
Research Site
Plovdiv, 4001, Bulgaria
Research Site
Sofia, 1680, Bulgaria
Research Site
Stara Zagora, 6000, Bulgaria
Research Site
London, Ontario, N6A 5A5, Canada
Research Site
Waterloo, Ontario, N2T 0C1, Canada
Research Site
Greenfield Park, Quebec, J4V 2H1, Canada
Research Site
Montreal, Quebec, H4J 1C5, Canada
Research Site
Baotou, 014010, China
Research Site
Beijing, 100029, China
Research Site
Beijing, 102218, China
Research Site
Changsha, 410013, China
Research Site
Chengdu, 610000, China
Research Site
Chengdu, 610072, China
Research Site
Chongqing, 400010, China
Research Site
Deyang, 618000, China
Research Site
Foshan, 528000, China
Research Site
Guangzhou, 510120, China
Research Site
Guangzhou, 510515, China
Research Site
Hangzhou, 310014, China
Research Site
Hengyang, 421001, China
Research Site
Linhai, 317000, China
Research Site
Nanjing, 210009, China
Research Site
Nanjing, 210011, China
Research Site
Nanning, 530022, China
Research Site
Ningbo, 315010, China
Research Site
Pingxiang, 337055, China
Research Site
Shanghai, 200240, China
Research Site
Shantou, 515041, China
Research Site
Shenzhen, 518039, China
Research Site
Shenzhen, 518053, China
Research Site
Wenzhou, 325000, China
Research Site
Wuhan, 430010, China
Research Site
Wuxi, 214000, China
Research Site
Xi'an, 710077, China
Research Site
Xiamen, 361101, China
Research Site
Yantai, 264000, China
Research Site
Yibin, 610500, China
Research Site
Yinchuan, 750004, China
Research Site
Zhuzhou, 412007, China
Research Site
Zigong, 643000, China
Research Site
Aalborg, 9100, Denmark
Research Site
Aarhus, 8200, Denmark
Research Site
Herlev, 2730, Denmark
Research Site
Herning, 7400, Denmark
Research Site
Roskilde, 4000, Denmark
Research Site
La Tronche, 38700, France
Research Site
Mulhouse, 68100, France
Research Site
Nice, 06000, France
Research Site
Nîmes, 30000, France
Research Site
Rouen, 76031, France
Research Site
Saint-Priest-en-Jarez, 42270, France
Research Site
Strasbourg, 67090, France
Research Site
Tours, 37000, France
Research Site
Aachen, 52074, Germany
Research Site
Bad Oeynhausen, 32545, Germany
Research Site
Berlin, 10117, Germany
Research Site
Dresden, 01279, Germany
Research Site
Hanover, 30625, Germany
Research Site
Mainz, 55131, Germany
Research Site
München, 80336, Germany
Research Site
Bangalore, 560060, India
Research Site
Belagavi, 590010, India
Research Site
Delhi, 110029, India
Research Site
Nadiād, 387001, India
Research Site
New Delhi, 110017, India
Research Site
Ashkelon, 78278, Israel
Research Site
Haifa, 3109601, Israel
Research Site
Jerusalem, 9372212, Israel
Research Site
Kfar Saba, 44281, Israel
Research Site
Nahariya, 22100, Israel
Research Site
Petah Tikva, 49372, Israel
Research Site
Ramat Gan, 52621, Israel
Research Site
Rehovot, 76100, Israel
Research Site
Bergamo, 24127, Italy
Research Site
Bologna, 40138, Italy
Research Site
Foggia, 71100, Italy
Research Site
Genoa, 16132, Italy
Research Site
Naples, 80138, Italy
Research Site
Pisa, 56124, Italy
Research Site
Roma, 161, Italy
Research Site
Torino, 10126, Italy
Research Site
Chūōku, 103-0027, Japan
Research Site
Fujisawa-shi, 251-0041, Japan
Research Site
Fukui-shi, 910-8526, Japan
Research Site
Fukuoka, 810-0001, Japan
Research Site
Fukuoka, 810-8563, Japan
Research Site
Fukuoka, 819-0168, Japan
Research Site
Hashima-gun, 501-6061, Japan
Research Site
Kamakura-shi, 247-0056, Japan
Research Site
Kasuga-shi, 816-0864, Japan
Research Site
Kawaguchi-shi, 332-0012, Japan
Research Site
Kitakyushu-shi, 802-8555, Japan
Research Site
Kitakyusyu-shi, 806-8501, Japan
Research Site
Kofu, 400-8506, Japan
Research Site
Kurume-shi, 830-0011, Japan
Research Site
Kurume-shi, 830-8543, Japan
Research Site
Kusatsu-shi, 525-8585, Japan
Research Site
Kyoto, 607-8062, Japan
Research Site
Matsumoto-shi, 390-8510, Japan
Research Site
Meguro-ku, 153-0061, Japan
Research Site
Minatoku, 108-0073, Japan
Research Site
Minokamo Shi, 505-8510, Japan
Research Site
Nishinomiya-Shi, 662-0918, Japan
Research Site
Nishinomiya-shi, 662-0971, Japan
Research Site
Okawa-shi, 831-0016, Japan
Research Site
Osaka, 550-0006, Japan
Research Site
Osaka, 559-0012, Japan
Research Site
Oyama-shi, 323-0022, Japan
Research Site
Sakushu, 385-8558, Japan
Research Site
Sapporo, 003-0026, Japan
Research Site
Sapporo, 062-0931, Japan
Research Site
Sendai, 980-8574, Japan
Research Site
Soka-shi, 340-0015, Japan
Research Site
Takamatsu, 760-0076, Japan
Research Site
Takasago-shi, 676-0812, Japan
Research Site
Tondabayashi-shi, 584-0082, Japan
Research Site
Toride-shi, 302-0022, Japan
Research Site
Urayasu, 279-0001, Japan
Research Site
Utsunomiya, 320-8580, Japan
Research Site
Alor Star, 5460, Malaysia
Research Site
Ipoh, 30990, Malaysia
Research Site
Kota Kinabalu, 88200, Malaysia
Research Site
Kuala Lumpur, 59100, Malaysia
Research Site
Seremban, 70300, Malaysia
Research Site
Seri Manjung, 32040, Malaysia
Research Site
Mazatlán, 82110, Mexico
Research Site
Amersfoort, 3813 TZ, Netherlands
Research Site
Breda, 4818 CK, Netherlands
Research Site
Dordrecht, 3318 AT, Netherlands
Research Site
Bodø, 8073, Norway
Research Site
Lørenskog, 1478, Norway
Research Site
Oslo, 0450, Norway
Research Site
Stavanger, 4011, Norway
Research Site
Tromsø, 9019, Norway
Research Site
Chrzanów, 32-500, Poland
Research Site
Krakow, 31-156, Poland
Research Site
Krakow, 31-501, Poland
Research Site
Lodz, 92-213, Poland
Research Site
Poznan, 60-354, Poland
Research Site
Radom, 26-600, Poland
Research Site
Rzeszów, 35-055, Poland
Research Site
Szczecin, 70-111, Poland
Research Site
Warsaw, 03-291, Poland
Research Site
Lučenec, 984 01, Slovakia
Research Site
Prešov, 080 01, Slovakia
Research Site
Púchov, 020 01, Slovakia
Research Site
Rožňava, 048 01, Slovakia
Research Site
Trebišov, 07501, Slovakia
Research Site
Benoni, 1501, South Africa
Research Site
Cape Town, 7925, South Africa
Research Site
Chatsworth, 4092, South Africa
Research Site
Durban, 4450, South Africa
Research Site
Lenasia, 1827, South Africa
Research Site
Midrand, 1685, South Africa
Research Site
Parow, 7505, South Africa
Research Site
Ansan-si, 15355, South Korea
Research Site
Busan, 49241, South Korea
Research Site
Cheonan-si, 31151, South Korea
Research Site
Daegu, 41944, South Korea
Research Site
Goyang-si, 10380, South Korea
Research Site
Seoul, 06591, South Korea
Research Site
Seoul, 120-752, South Korea
Research Site
Seoul, 156-707, South Korea
Research Site
Girona, 17007, Spain
Research Site
L'Hospitalet de Llobregat, 08907, Spain
Research Site
Lugo, 27004, Spain
Research Site
Madrid, 28041, Spain
Research Site
Majadahonda, 28222, Spain
Research Site
Seville, 41071, Spain
Research Site
Valencia, 46010, Spain
Research Site
Gothenburg, 413 46, Sweden
Research Site
Linköping, 581 85, Sweden
Research Site
Rättvik, 79530, Sweden
Research Site
Stockholm, 141 86, Sweden
Research Site
Uppsala, 751 85, Sweden
Research Site
Kaohsiung City, 807, Taiwan
Research Site
Kaohsiung City, 833, Taiwan
Research Site
New Taipei City, 220, Taiwan
Research Site
Taichung, 40705, Taiwan
Research Site
Tainan, 710, Taiwan
Research Site
Taipei, 10002, Taiwan
Research Site
Taipei, 110, Taiwan
Research Site
Taipei, 11490, Taiwan
Research Site
Taoyuan District, 333, Taiwan
Research Site
Bangkok, 10330, Thailand
Research Site
Bangkok, 10700, Thailand
Research Site
Chaingmai, 50200, Thailand
Research Site
Hat Yai, 90110, Thailand
Research Site
Khon Kaen, 40002, Thailand
Research Site
Ratchathewi, 10400, Thailand
Research Site
Adapazarı, 54100, Turkey (Türkiye)
Research Site
Ankara, 06230, Turkey (Türkiye)
Research Site
Bursa, 16059, Turkey (Türkiye)
Research Site
Dinar, 03400, Turkey (Türkiye)
Research Site
Kahramanmaraş, 46040, Turkey (Türkiye)
Research Site
Kayseri, 38039, Turkey (Türkiye)
Research Site
Kocaeli, 41380, Turkey (Türkiye)
Research Site
Cardiff, CF14 4XW, United Kingdom
Research Site
Dundee, DD1 9SY, United Kingdom
Research Site
Glasgow, G51 4TF, United Kingdom
Research Site
London, EC1A 2BE, United Kingdom
Research Site
London, NW3 2QG, United Kingdom
Research Site
London, SE5 9RJ, United Kingdom
Research Site
York, YO21 8HE, United Kingdom
Research Site
Haiphong, 180000, Vietnam
Research Site
Hanoi, 10000, Vietnam
Research Site
Ho Chi Minh City, 700000, Vietnam
Research Site
Ho Chi Minh City, 70000, Vietnam
Research Site
Ho Chi Minh City, Vietnam
Related Publications (1)
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.
PMID: 39352861DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 4, 2023
First Posted
October 18, 2023
Study Start
November 7, 2023
Primary Completion (Estimated)
February 18, 2027
Study Completion (Estimated)
February 18, 2027
Last Updated
March 25, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.