Zibotentan and Dapagliflozin for the Treatment of Chronic Kidney Disease (ZENITH-CKD trial)
- Conditions
- Chronic Kidney DiseaseTherapeutic area: Body processes [G] - Metabolic Phenomena [G03]MedDRA version: 23.1Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disorders
- Registration Number
- EUCTR2020-004101-32-ES
- Lead Sponsor
- AstraZeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 660
Type of Participant and Disease Characteristics / Laboratory Parameters
1. Diagnosis of CKD, defined as:
(a) Part A: eGFR (CKD-EPI) = 30 and = 60 mL/min/1.73 m2
Part B, if safety data from Part A allow (otherwise same as in Part A):
eGFR
(CKD-EPI) = 20 and = 60 mL/min/1.73 m2
2. Urine albumin to creatinine ratio (UACR) = 200 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 On a stable dose of ACEi and/or ARB (= 4 weeks before screening).
5 No current or prior treatment within 3 months prior to screening with cytotoxic therapy, immunosuppressive therapy or other immunotherapy.
Weight
6 Body mass index (BMI) = 40 kg/m2 .
Sex
7 Male or female of non-childbearing potential.
Reproduction
8 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:
(a) Postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH and LH levels in the postmenopausal range.
(b) Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
9 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 330
Medical Conditions
1 Minimal change disease, unstable rapidly progressing renal disease, and/or renal disease requiring significant immunosuppression, autosomal dominant or autosomal recessive polycystic kidney disease, or anatomical causes of CKD.
2 History of epilepsy syndrome.
3 Participants with NYHA functional HF class III or IV.
4 Acute coronary syndrome (ACS) events within 3 months prior to screening.
5 Participants with a confirmed BNP = 200 pg/mL or BNP = 400 pg/mL if with atrial fibrillation.
6 Participants with unstable HF requiring hospitalisation for optimization of HF treatment and/or who have not been stable on HF therapy within 6 months prior to screening.
7 Heart failure due to cardiomyopathies that would primarily require specific other 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).
8 High output HF (eg, due to hyperthyroidism or Paget's disease).
9 Heart failure due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement.
10 Participants with uncontrolled diabetes mellitus (HbA1c > 12%).
11 Participants with T1DM.
12 Hyponatremia, defined as serum Na+ < 135 mmol/L at the time of randomisation.
13 Intermittent or persistent second or third degree atrioventricular(AV) block after sinus node dysfunction, with clinically significant bradycardia or sinus pause when not treated with pacemaker.
14 Prolonged QT interval (QTcF > 470ms) on ECG at randomisation visit (Visit 2), known congenital long QT syndrome or history of QTprolongation associated with other medications.
15 History of any life-threatening cardiac dysrhythmia (continuous or paroxysmal or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter).
16 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 12 months) prior to screening or is planned to undergo any of these procedures after randomisation.
17 Heart transplantation or left ventricular assist device at any time.
18 Kidney or any organ transplantation.
19 History or ongoing allergy/hypersensitivity, as judged by theinvestigator, to SGLT2i (eg, dapagliflozin, canagliflozin, empagliflozin) or drugs with a similar chemical structure to zibotentan.
20 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 = 25 mmHg at rest)
or right ventricular failure; in the absence of left-sided HF.
(b) Anaemia defined as haemoglobin (Hb) level < 100 g/L or 10 g/dL at randomization visit (Visit 2).
(c) Severe chronic obstructive pulmonary disease (COPD) or other lung disease including but not limited to pulmonary fibrosis requiring chronic O2therapy, regula
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method