Health Condition 1: N189- Chronic kidney disease, unspecified
Conditions
Interventions
Intervention1: Baxdrostat + Dapagliflozin: Baxdrostat 1 mg and dapagliflozin 10 mg
Baxdrostat 2 mg and dapagliflozin 10 mg
One tablet of baxdrostat and one tablet of dapagliflozin once daily
Control
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1 Participants of any sex and gender must be � 18 years old, or older, at the time of signing the informed consent. 2 eGFR � 30 and less than 90 mL/min/1.73 m2 at screening 3 Urine albumin creatinine ratio greater than 200 mg/g (22.6 mg/mmol) and less than 5000 mg/g (565 mg/mmol) at screening 4 Participants with history of HTN and a SBP � 130 mmHg at screening and � 120 mmHg at the randomisation visit 5 Stable and maximum daily tolerated dose of an ACE inhibitor or an ARB (not both) for at least 4 weeks prior to Screening Visit 6 Central laboratory serum potassium must meet the following criteria at the Screening Visit, based on screening eGFR: a. for participants with screening eGFR � 45 mL/min/1.73 m2, potassium must be � 3.5 and � 4.8 mmol/L at the Screening Visit b. for participants with screening eGFR less than 45 mL/min/1.73 m2, potassium must be � 3.5 and � 4.5 mmol/L at the Screening Visit 7 Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 8 Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. 9 Provision of signed and dated written informed consent prior to any study specific procedure (pre-screening ICF and ICF collected at screening). 10 Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of optional genetic samples for Genomics Initiative research that supports the Genomic Initiative.
Exclusion criteria
Exclusion criteria: 1 Systolic blood pressure greater than 180 mmHg, or diastolic BP greater than 110 mmHg at screening. 2 Known hyperkalaemia, defined as potassium of � 5.5 mmol/L within 3 months at screening. 3 Serum sodium less than 135 mmol/L at the Screening Visit, determined as per central laboratory. 4 Type 1 diabetes mellitus or uncontrolled Type 2 diabetes mellitus with HbA1c greater than 10.5% (greater than 91 mmol/mol) at Screening. 5 New York Heart Association functional HF class IV at screening. 6 Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, or carotid angioplasty, acute coronary syndrome, or hospitalisation for worsening heart failure within previous 3 months prior to randomisation. 7 Baseline QTcF greater than 470 msec. 8 Family history of Long QT syndrome. 9 Known severe hepatic impairment, defined as Child-Pugh Class C, based on records that confirm documented medical history. 10 Documented history of adrenal insufficiency. 11 Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit. 12 Any acute kidney injury within 3 months prior to the Screening Visit. 13 Known hypersensitivity to the study treatment (active substance or excipients). 14 History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant). 15 History or ongoing allergy/hypersensitivity, as judged by the Investigator, to SGLT2 inhibitor (eg, empagliflozin) or ASI. 16 Any clinical condition requiring systemic immunosuppression therapy other than maintenance therapy (stable for at least 3 months prior to Visit 1). 17 Drug or alcohol abuse that in the Investigator s judgement makes the participant a poor candidate for the study. 18 Any use of mineralocorticoid receptor antagonists (such as spironolactone, eplerenone, or finerenone), potassium-sparing diuretics (such as triamterene or amiloride), or potassium binders (such as sodium zirconium cyclosilicate, patiromer, or sodium polystyrene sulfonate) within 4 weeks prior to screening. 19 Concomitant therapy with strong inducers of cytochrome P450 (CYP) 3 A (eg, apalutamide, avasimibe, carbamazepine, enzalutamide, lumacaftor, mitotane, phenytoin, rifampin, rifapentine, St. John s wort). 20 Drugs that prolong QT should be avoided, if possible, and if there are other alternatives which are not expected to prolong QT, these should be preferred. If such QT prolonging drugs are still needed, the Investigator must ensure appropriate monitoring of ECGs and electrolytes are performed, as per clinical judgement. 21 Any other condition or therapy, in the judgement of the Investigator or the Sponsor, which would make the participant unsuitable for this study, including a condition or therapy which the Investigator anticipates will not allow participation for the full planned study period (eg, active malignancy or other condition limiting life expectancy to less than 12 months). 22 Participation in another clinical study with an investigational product administered in the last 3 months prior to randomisation. 23 Involvement in the planning and/or conduct of the study (applies to both AZ personnel and/or site personnel). 24 For WOCB
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone to slow CKD progression, assessed as the effect on change in eGFRTimepoint: Change from baseline in eGFR to post treatment at 2 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone at reducing UACRTimepoint: Change from baseline in UACR at 16 weeks.;To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone at reducing SBP.Timepoint: Change from baseline in mean SBP at 16 weeks.;To determine whether baxdrostat/dapagliflozin compared with dapagliflozin alone slows CKD progression and reduces the risk of ESKD.Timepoint: Kidney hierarchical composite endpointa;To determine whether baxdrostat/dapagliflozin compared with dapagliflozin alone slows the rate of kidney function decline after the haemodynamically- mediated acute effect on eGFR.Timepoint: Change in eGFR from 8 weeks following randomisation to end of treatment | — |
Countries
Argentina, Austria, Belgium, Botswana, Bulgaria, Canada, Chile, China, Czech Republic, Denmark, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Malaysia, Netherlands, Peru, Philippines, Poland, Republic of Korea, Romania, Saudi Arabia, Serbia, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States of America, Viet Nam
Contacts
Public ContactTapankumar M Shah
AstraZeneca Pharma India Ltd
Outcome results
None listed