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 m2 - Zenith-CKD

AstraZeneca0 sites495 target enrollmentMarch 23, 2021

DrugsForxiga

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: AstraZeneca
Enrollment: 495
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

March 23, 2021

End Date

TBD

Last Updated

2 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

AstraZeneca

Eligibility Criteria

Inclusion Criteria

•Type of Participant and Disease Characteristics / Laboratory Parameters Diagnosis of CKD, defined as:
•1\. eGFR (CKD\-EPI) \= 20 mL/min/1\.73 m2
•2\. Urine albumin to creatinine ratio (UACR) \= 150 and \= 5000 mg albumin/g creatinine, based on a single first morning void spot urine sample at screening
•Medical Treatment
•3\. No current or prior (within 1 month of screening) medical treatment with an SGLT2i or any FDC with SGLT2i (such as SGLT2i \+ metformin).
•4\. If ACEi and/or ARB and/or MRA 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.
•5\. 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.
•6\. Body mass index (BMI) \= 40 kg/m2\.
•7\. Male or female of non\-childbearing potential.
•Reproduction

Exclusion Criteria

•1\.Minimal change disease, unstable rapidly progressing renal disease, and/or renal disease requiring significant immunosuppression, autosomal dominant or autosomal recessive polycystic kidney disease.
•2\.Participants with NYHA functional HF class III or IV. 3\.Acute coronary syndrome events within 3 months prior to screening. 4\.Participants with a BNP\=200pg/mL or NT proBNP\=600pg/mL (BNP\=400pg/mL or NT\-proBNP\=1200pg/mL, respectively, if associated with atrial fibrillation) measured by local laboratory at screening (Visit 1\). 5\.Participants with unstable HF requiring hospitalisation for optimizationof HF treatment and/or who have not been stable on HF therapy within 6months prior to screening. 6\.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. 7\.High output HF (eg, due to hyperthyroidism or Paget's disease). 8\.Heart failure due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement. 9\.Participants with uncontrolled diabetes mellitus (HbA1c\>12%). 10\.Participants with T1DM. 11\.Hyponatremia, defined as serum Na\+\<135mmol/L at the time of screening (Visit 1\). 12\.Intermittent or persistent second or third degree AV block after sinusnode dysfunction, with clinically significant bradycardia or sinus pause when not treated with pacemaker. 13\.Prolonged QT interval (QTcF\>470ms) 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. 14\.History of any life\-threatening cardiac dysrhythmia (continuous or paroxysmal or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter). 15\.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. 16\.Heart transplantation or left ventricular assist device at any time. 17\.Kidney or any organ transplantation. 18\.History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2i (eg, dapagliflozin, canagliflozin, empagliflozin) ordrugs with a similar chemical structure to zibotentan. 19\.Any clinically significant disease or disorder (eg, cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, psychiatric, major physical impairment) which, as judged by the investigator, 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: (a)Isolated pulmonary arterial hypertension (defined as mean PAP\= 25mmHg at rest) or right ventricular failure; in the absence of left\-sided HF. (b)Anaemia defined as Hb level \<100g/L or 10g/dL at screening (Visit 1\). (c)Severe COPD or other lung disease including but not limited to pulmonary fibrosis requiring chronic O2 therapy, regular nebuliser use, or oral steroid therapy. 20\.Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within previous