Zibotentan and Dapagliflozin for the Treatment of CKD (ZENITH-CKD Trial) (ZENITH-CKD)

A Phase 2b Multicentre, Randomised, Double-Blind, Active-Controlled, Parallel Group Dose-Ranging Study to Assess the Efficacy, Safety and Tolerability of Zibotentan and Dapagliflozin in Patients With Chronic Kidney Disease With Estimated Glomerular Filtration Rate (eGFR) ≥ 20 mL/Min/1.73 m^2

The purpose of the study is to assess efficacy, safety and tolerability of treatment with zibotentan and dapagliflozin in combination and dapagliflozin 10 mg as monotherapy in participants with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m^2, and urinary albumin to creatinine ratio (UACR) ≥ 150 mg/g and ≤ 5000 mg/g.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Zibotentan; Drug: Placebo; Drug: Dapagliflozin

Detailed Description

The study will be conducted in approximately 220 sites in North America, South America, Africa, Asia/Pacific, and European countries.

Participants will be randomized to 12 weeks of treatment plus 2 weeks follow-up.

After screening, eligible participants will be stratified by diabetes (diabetic kidney disease [DKD] versus non-diabetes mellitus [non-DM] CKD) and baseline eGFR (below or equal versus above 45 mL/min/1.73m^2).

A total of 495 participants will be randomised into this study, including participants randomised under the earlier study design. Four hundred and fifteen (415) participants will be randomised to have 166 participants in zibotentan Dose A/dapagliflozin 10 mg combination arm and dapagliflozin 10 mg monotherapy arm, and 83 participants in the zibotentan Dose B/dapagliflozin 10 mg combination arm.

• Zibotentan Dose A + Dapagliflozin 10 mg once daily.
• Zibotentan Dose B + Dapagliflozin 10 mg once daily.
• Placebo + Dapagliflozin 10 mg once daily

Participants who were previously randomised cannot be re-randomised.

• Study Type: Interventional
• Enrollment (Actual): 542
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B7600FYW
    • Research Site
  • Buenos Aires, Argentina, C1425AGC
    • Research Site
  • Caba, Argentina, C1440AAD
    • Research Site
  • Caba, Argentina, C1120AAC
    • Research Site
  • Cordoba, Argentina, 5003
    • Research Site
  • Corrientes, Argentina, W3400AMZ
    • Research Site
  • Junín, Argentina, 6000
    • Research Site
  • Mar del Plata, Argentina, B7600FZN
    • Research Site
  • San Luis, Argentina, 5700
    • Research Site
  • San Miguel de Tucuman, Argentina, 4000
    • Research Site
  • Santa Fe, Argentina, S3000
    • Research Site
• Australia
  • Adelaide, Australia, 5000
    • Research Site
  • Birtinya, Australia, 4575
    • Research Site
  • Elizabeth Vale, Australia, 5112
    • Research Site
  • Gosford, Australia, 2250
    • Research Site
  • Westmead, Australia, 2145
    • Research Site
• Brazil
  • Botucatu, Brazil, 18618-687
    • Research Site
  • Campinas, Brazil, 13010-001
    • Research Site
  • Curitiba, Brazil, 80440-020
    • Research Site
  • Porto Alegre, Brazil, 90020-090
    • Research Site
  • Santo Andre, Brazil, 09090-790
    • Research Site
  • Sao Paulo, Brazil, 04039-000
    • Research Site
  • Sao Paulo, Brazil, 5403-000
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 01228-200
    • Research Site
• Bulgaria
  • Gabrovo, Bulgaria, 5300
    • Research Site
  • Kozloduy, Bulgaria, 3320
    • Research Site
  • Montana, Bulgaria, 3400
    • Research Site
  • Plovdiv, Bulgaria, 4023
    • Research Site
  • Sliven, Bulgaria, 8800
    • Research Site
  • Sofia, Bulgaria, 1407
    • Research Site
  • Sofia, Bulgaria, 1510
    • Research Site
  • Stara Zagora, Bulgaria, 6000
    • Research Site
• Canada
  • Ontario
    • London, Ontario, Canada, N6A-5A5
      • Research Site
    • Toronto, Ontario, Canada, M5N 1C1
      • Research Site
    • Waterloo, Ontario, Canada, N2T 0C1
      • Research Site
• Croatia
  • Pula, Croatia, 52000
    • Research Site
  • Vinkovci, Croatia, 32100
    • Research Site
• Denmark
  • Gentofte, Denmark, 2820
    • Research Site
  • Roskilde, Denmark, 4000
    • Research Site
  • Århus N, Denmark, 8200
    • Research Site
• Georgia
  • Batumi, Georgia, 6010
    • Research Site
  • Gori, Georgia, 1400
    • Research Site
  • Gurjaani, Georgia, 1500
    • Research Site
  • Kutaisi, Georgia, 4600
    • Research Site
  • Marneuli, Georgia, 3000
    • Research Site
  • Tbilisi, Georgia, 0144
    • Research Site
  • Tbilisi, Georgia, 0159
    • Research Site
  • Tbilisi, Georgia, 112
    • Research Site
  • Tbilisi, Georgia, 0102
    • Research Site
  • Tbilisi, Georgia, 0114
    • Research Site
• Hungary
  • Debrecen, Hungary, 4032
    • Research Site
  • Hatvan, Hungary, 3000
    • Research Site
  • Miskolc, Hungary, 3530
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Genova, Italy, 16132
    • Research Site
  • Germaneto, Italy, 88100
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Napoli, Italy, 80138
    • Research Site
  • Napoli, Italy, 80035
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
  • San Giovanni Rotondo, Italy, 71013
    • Research Site
• Japan
  • Chiba-shi, Japan, 260-8712
    • Research Site
  • Chuo-ku, Japan, 103-0027
    • Research Site
  • Koshigaya-shi, Japan, 343-8577
    • Research Site
  • Nagoya, Japan, 455-8530
    • Research Site
  • Naka, Japan, 311-0113
    • Research Site
  • Osaka-shi, Japan, 530-0001
    • Research Site
  • Osaka-shi, Japan, 558-8558
    • Research Site
  • Osaka-shi, Japan, 559-0012
    • Research Site
  • Takarazuka-shi, Japan, 665-0861
    • Research Site
  • Tsu-shi, Japan, 514-1101
    • Research Site
  • Ueda-shi, Japan, 386-8610
    • Research Site
  • Yao-shi, Japan, 581-0011
    • Research Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Research Site
  • Kuantan, Malaysia, 25200
    • Research Site
• Netherlands
  • Breda, Netherlands, 4800 RK
    • Research Site
  • Dordrecht, Netherlands, 3300 AK
    • Research Site
• Poland
  • Bialystok, Poland, 15-375
    • Research Site
  • Krakow, Poland, 31-261
    • Research Site
  • Oświęcim, Poland, 32-600
    • Research Site
  • Poznań, Poland, 60-848
    • Research Site
  • Rzeszow, Poland, 35-055
    • Research Site
• Slovakia
  • Rimavska Sobota, Slovakia, 979 01
    • Research Site
• South Africa
  • Bellville, South Africa, 7530
    • Research Site
  • Bloemfontein, South Africa, 9301
    • Research Site
  • Durban, South Africa, 4001
    • Research Site
  • George, South Africa, 6529
    • Research Site
  • Observatory, South Africa, 7925
    • Research Site
  • Pretoria, South Africa, 0157
    • Research Site
  • Pretoria, South Africa, 0181
    • Research Site
  • Somerset West, South Africa, 7130
    • Research Site
• Spain
  • A Coruna, Spain, 15006
    • Research Site
  • Barcelona, Spain, 08035
    • Research Site
  • Burela, Spain, 27880
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Malaga, Spain, 29010
    • Research Site
  • Palma de Mallorca, Spain, 07010
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
  • Valencia, Spain, 46010
    • Research Site
  • Valencia, Spain, 46017
    • Research Site
• Ukraine
  • Chernivtsі, Ukraine, 58022
    • Research Site
  • Dnipro, Ukraine, 49102
    • Research Site
  • Kharkiv, Ukraine, 61103
    • Research Site
  • Kyiv, Ukraine, 03049
    • Research Site
  • Kyiv, Ukraine, 1004
    • Research Site
  • Ternopil, Ukraine, 46002
    • Research Site
  • Uzhhorod, Ukraine, 88018
    • Research Site
  • Vinnytsia, Ukraine, 21001
    • Research Site
  • Zaporizhia, Ukraine, 69001
    • Research Site
  • Zhytomyr, Ukraine, 10002
    • Research Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Research Site
  • California
    • Beverly Hills, California, United States, 90211
      • Research Site
    • Downey, California, United States, 90242
      • Research Site
    • Fountain Valley, California, United States, 92708
      • Research Site
    • Laguna Hills, California, United States, 92653
      • Research Site
    • Los Angeles, California, United States, 90057
      • Research Site
    • Northridge, California, United States, 91324
      • Research Site
    • Ontario, California, United States, 91762
      • Research Site
    • S. Gate, California, United States, 90280
      • Research Site
    • Tarzana, California, United States, 91356
      • Research Site
    • Vacaville, California, United States, 95687
      • Research Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Research Site
    • Hialeah, Florida, United States, 33012
      • Research Site
    • New Port Richey, Florida, United States, 34652
      • Research Site
    • Orlando, Florida, United States, 32806
      • Research Site
    • Riverview, Florida, United States, 33578
      • Research Site
    • Tampa, Florida, United States, 33614
      • Research Site
  • Georgia
    • Augusta, Georgia, United States, 30904
      • Research Site
    • Fayetteville, Georgia, United States, 30214
      • Research Site
  • Kansas
    • Wichita, Kansas, United States, 67214-2943
      • Research Site
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Research Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Research Site
    • Shreveport, Louisiana, United States, 71101
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Michigan
    • Flint, Michigan, United States, 48504
      • Research Site
    • Flint, Michigan, United States, 48532
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Research Site
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Research Site
    • Jacksonville, North Carolina, United States, 28546
      • Research Site
    • Kinston, North Carolina, United States, 28504
      • Research Site
    • Morehead City, North Carolina, United States, 28557
      • Research Site
    • New Bern, North Carolina, United States, 28562
      • Research Site
    • Wilmington, North Carolina, United States, 28401
      • Research Site
  • Ohio
    • Marion, Ohio, United States, 43302
      • Research Site
  • Pennsylvania
    • Chester, Pennsylvania, United States, 19013
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Site
    • Memphis, Tennessee, United States, 38104
      • Research Site
  • Texas
    • Arlington, Texas, United States, 76002
      • Research Site
    • Conroe, Texas, United States, 77384
      • Research Site
    • Corpus Christi, Texas, United States, 78414
      • Research Site
    • El Paso, Texas, United States, 79935
      • Research Site
    • Houston, Texas, United States, 77004
      • Research Site
    • Houston, Texas, United States, 77099
      • Research Site
    • Odessa, Texas, United States, 79761
      • Research Site
    • San Antonio, Texas, United States, 78212
      • Research Site
    • Waxahachie, Texas, United States, 75165
      • Research Site
  • Virginia
    • Forest, Virginia, United States, 24551
      • Research Site
    • Newport News, Virginia, United States, 23606
      • Research Site
  • Washington
    • Spokane, Washington, United States, 99204
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

• Diagnosis of Chronic kidney disease (CKD), defined as:

  (a) eGFR chronic kidney disease epidemiology collaboration (CKD-EPI) ≥ 20 mL/min/1.73 m^2, and (b) UACR ≥ 150 and ≤ 5000 mg albumin/g creatinine, based on a single first morning void spot urine sample at screening.

• No current or prior (within 1 month of screening) medical treatment with an SGLT2i (sodium-glucose co-transporter 2 inhibitor) or any fixed dose combination with SGLT2i.
• If Angiotensin-converting enzyme inhibitors (ACEi) and/or Angiotensin receptor blockers (ARB) and/or mineralocorticoid receptor agonist are prescribed, the dose must be stable ≥ 4 weeks before screening. Participants who have been deemed unable to tolerate ACEi or ARB therapy due to allergy or complications can be enrolled.
• No current or prior treatment within 6 months prior to screening with cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary kidney disease.
• Body mass index ≤ 40 kg/m^2.
• Male or female of non-childbearing potential.

• Female participants must have a negative pregnancy test at screening, must not be lactating, and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:

  • Postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range.
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
• Male participants must be surgically sterile, abstinent, or in conjunction with a female sexual partner, using a highly effective method of contraception for the duration of the study (from the time they sign consent) and for 3 months after the last dose of investigational product to prevent any pregnancies. Male study participants must not donate or bank sperm during this same time period.
• Capable of giving signed informed consent, as described in Appendix A, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Provision of signed and dated, written ICF prior to any mandatory study-specific procedures, sampling, and analyses.
• Provision of signed and dated written Genetic informed consent prior to collection of samples (optional) for genetic analysis.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Minimal change disease, unstable rapidly progressing renal disease, and/or renal disease requiring significant immunosuppression, autosomal dominant or autosomal recessive polycystic kidney disease.
• Participants with New York Heart Association classification functional heart failure (HF) class III or IV.
• Acute coronary syndrome events within 3 months prior to screening.
• Participants with a B-type natriuretic peptide (BNP) ≥ 200 pg/mL or NT-proBNP ≥ 600 pg/mL (BNP ≥ 400 pg/mL or NT-proBNP ≥ 1200 pg/mL, respectively, if associated with atrial fibrillation) measured by local laboratory at screening (Visit 1).
• Participants with unstable HF requiring hospitalisation for optimisation of HF treatment and/or who have not been stable on HF therapy within 6 months prior to screening
• Heart failure due to cardiomyopathies that would primarily require other specific treatment: eg, cardiomyopathy due to pericardial disease, amyloidosis or other infiltrative diseases, cardiomyopathy related to congenital heart disease, primary hypertrophic cardiomyopathy, cardiomyopathy related to toxic or infective conditions (ie, chemotherapy, infective myocarditis, septic cardiomyopathy).
• High output HF (eg, due to hyperthyroidism or Paget's disease).
• Heart failure due to primary cardiac valvular disease/ dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement.
• Participants with uncontrolled diabetes mellitus (HbA1c > 12%).
• Participants with Type 1 diabetes mellitus.
• Hyponatremia, defined as serum Na+ < 135 mmol/L at the time of screening (Visit 1).
• Intermittent or persistent second or third degree atrioventricular block after sinus node dysfunction, with clinically significant bradycardia or sinus pause when not treated with pacemaker.
• Prolonged QT interval (QTcF > 470 ms) on ECG at screening (Visit 1) or randomisation visit (Visit 2), known congenital long QT syndrome or history of QT prolongation associated with other medications.
• History of any life-threatening cardiac dysrhythmia (continuous or paroxysmal or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter).
• Cardiac surgery or non-elective percutaneous coronary interventions (PCI/TAVI) (within 3 months) or open chest coronary artery bypass grafting or valvular repair/replacement (within 3 months) prior to screening or is planned to undergo any of these procedures after randomisation.
• Heart transplantation or left ventricular assist device at any time.
• Kidney or any organ transplantation.
• History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2i (eg, dapagliflozin, canagliflozin, empagliflozin) or drugs with a similar chemical structure to zibotentan.

• Any clinically significant disease or disorder (eg, cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, psychiatric, major physical impairment), which might put the participant at risk because of participation in the study, or probable alternative primary reason for participant's symptoms in judgment of investigator, including but not limited to:

  • Isolated pulmonary arterial hypertension [PAP] (defined as mean PAP ≥ 25 mmHg at rest) or right ventricular failure; in the absence of left-sided HF
  • Anaemia defined as haemoglobin (Hb) level < 100 g/L or 10 g/dL at screening (Visit 1)
  • Severe chronic obstructive pulmonary disease or other lung disease including but not limited to pulmonary fibrosis requiring chronic oxygen therapy, regular nebuliser use, or oral steroid therapy
• Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within previous 3 months prior to screening.
• Severe hepatic impairment (Child-Pugh class C Hepatic impairment), aspartate transaminase or alanine transaminase > 2x the upper limit of normal [ULN]; or total bilirubin > 2x ULN at time of screening.
• Participants with newly detected pathological laboratory values or an ongoing disease condition requiring investigation and/or initiation or adjustment of current treatment (in the opinion of the investigator).
• Positive hepatitis C antibody, or hepatitis B virus, surface antigen at screening.
• Positive human immunodeficiency virus (HIV) test.
• Participants treated with strong or moderate CYP3A4 inhibitor or inducer.
• Any condition outside the renal and CV disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator's clinical judgment.

• Confirmation of corona virus disease- 2019 (COVID-19) infection:

  • Participant has a positive test result for severe acute respiratory syndrome coronavirus 2 during screening. Participants who are not hospitalised for COVID-19 infections can be re screened 4 weeks after they have recovered.
  • Participant has been previously hospitalised with COVID-19 infection.
• Ejection fraction < 50% measured by echocardiogram at screening.
• Participation in another clinical study with an investigational product administered in the last 3 months prior to screening.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
• Previous randomisation into the present study.
• Plasma donation within 1 month of the visit at the clinic or any blood donation/blood loss > 500 mL during the 3 months prior to any visit at the clinic.
• Male participant in a sexually active relation with pregnant or breastfeeding partner.

• Participants can decline to participate in the genetic research and may still participate in the study. Exclusion from this optional genetic research may be for any of the exclusion criteria specified for the main study or any of the following:

  • Previous allogeneic bone marrow transplant.
  • Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zibotentan Dose A + Dapagliflozin; Participants will receive once daily oral dose A of zibotentan and 10 mg dapagliflozin for 12 weeks.	Drug: Zibotentan; Participants will receive zibotentan as per the arms they are randomized.; Drug: Dapagliflozin; Participants will receive 10 mg dapagliflozin as per the arms they are randomized.
Experimental: Zibotentan Dose B + Dapagliflozin; Participants will receive once daily oral dose B of zibotentan and 10 mg dapagliflozin for 12 weeks.	Drug: Zibotentan; Participants will receive zibotentan as per the arms they are randomized.; Drug: Dapagliflozin; Participants will receive 10 mg dapagliflozin as per the arms they are randomized.
Experimental: Placebo + Dapagliflozin; Participants will receive once daily oral dose of dapagliflozin 10 mg and placebo for 12 weeks.	Drug: Placebo; Participants will receive placebo as per the arms they are randomized to.; Drug: Dapagliflozin; Participants will receive 10 mg dapagliflozin as per the arms they are randomized.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Log-transformed Urinary Albumin to Creatinine Ratio (UACR) from baseline to Week 12	The effect of zibotentan Dose B/dapagliflozin 10 mg versus dapagliflozin 10 mg on UACR will be assessed.	From baseline (Week 0 [Day 1]) until Week 12 (Day 84)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Log-transformed UACR from baseline to Week 12	The effect of zibotentan dose A/dapagliflozin 10 mg versus dapagliflozin 10 mg monotherapy on UACR will be assessed.	From baseline (Week 0 [Day 1]) until Week 12 (Day 84)
Change in Blood Pressure from baseline to Week 12	The change in office systolic and diastolic blood pressure (BP) for doses of zibotentan combined with dapagliflozin 10 mg versus dapagliflozin 10 mg monotherapy will be assessed.	From baseline (Week 0 [Day 1]) until Week 12 (Day 84)
Change in eGFR from Baseline to Week 1, Week 12 and Week 14	The effect of different doses of zibotentan and dapagliflozin 10 mg in combination versus dapagliflozin 10 mg monotherapy on eGFR will be assessed.	From baseline (Week 0 [Day 1]) until Week 1, Week 12, and Week 14
Change in eGFR from Week 1 to Week 12	The effect of different doses of zibotentan and dapagliflozin 10 mg in combination versus dapagliflozin 10 mg monotherapy on eGFR will be assessed.	From Week 1 (Day 8) until Week 12 (Day 84)
Number of Participants Experiencing Adverse events	The safety and tolerability of all doses of zibotentan combined with dapagliflozin 10 mg and dapagliflozin 10 mg monotherapy will be assessed.	From Week 0 (Day 1) until Follow-up visit (Week 14 [Day 98])
Change in log-transformed UACR from baseline to Week 12	The assessment of dose-response and relationship across different dose of zibotentan/dapagliflozin and dapagliflozin alone on UACR reduction.	From baseline until Week 12 (Day 84)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: David C Wheeler, MB ChB, MD, FRCP, Centre for Nephrology Royal Free Campus University College London Rowland Hill Street London NW3 2PF United Kingdom; Principal Investigator: Jamie P. Dwyer, M.D., Nephrology Clinical Trials Center Nephrology and Hypertension Vanderbilt University Medical Center Nashville TN United States of America

Publications and helpful links

General Publications

• Smeijer JD, Kohan DE, Webb DJ, Dhaun N, Heerspink HJL. Endothelin receptor antagonists for the treatment of diabetic and nondiabetic chronic kidney disease. Curr Opin Nephrol Hypertens. 2021 Jul 1;30(4):456-465. doi: 10.1097/MNH.0000000000000716.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2021
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 25, 2021
• First Posted (Actual): January 26, 2021

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Dapagliflozin; Nephrology; Kidney diseases; Zibotentan; Sodium-glucose co-transporter 2; sodium-glucose co-transporter 2 inhibitor; Endothelin antagonist
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: D4325C00001; 2020-004101-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

IPD Sharing 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.

IPD Sharing 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.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No