A trial to learn how well baxdrostat with dapagliflozin works compared to dapagliflozin alone and how safe it is in adults with chronic kidney disease (CKD) and high blood pressure

Phase 1

Recruiting

Conditions: MedDRA version: 23.1Level: PTClassification code: 10064848Term: Chronic kidney disease Class: 100000004857
MedDRA version: 20.0Level: PTClassification code: 10020772Term: Hypertension Class: 100000004866
Chronic kidney disease (CKD) and hypertension.
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: CTIS2023-506457-38-00

Lead Sponsor: Astrazeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 2500

Inclusion Criteria

Participants of any sex and gender must be = 18 years old, or older, at the time of signing the informed consent., Participants with CKD and eGFR = 30 and < 90 mL/min/1.73 m2 at screening, Urine albumin creatinine ratio > 200 mg/g (22.6 mg/mmol) and < 5000 mg/g (565 mg/mmol) at screening, Participants with history of HTN and a SBP = 130 mmHg at screening and = 120 mmHg at the randomisation visit, Stable and maximum tolerated dose of an ACE inhibitor or an ARB (not both) for at least 4 weeks prior to Screening Visit, Central laboratory serum potassium must meet the following criteria at the Screening Visit, based on screening eGFR: o 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 o for participants with screening eGFR < 45 mL/min/1.73 m2, potassium must be = 3.5 and = 4.5 mmol/L at the Screening Visit

Exclusion Criteria

Medical Conditions 1. Systolic blood pressure > 180 mmHg, or DBP > 110 mmHg at screening., History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2 inhibitor (eg, empagliflozin) or ASI., Any clinical condition requiring systemic immunosuppression therapy other than stable maintenance therapy for at least 3 months prior to Visit 1., 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., Known hyperkalaemia, defined as potassium of = 5.5 mmol/L within 3 months at screening., Serum sodium < 135 mmol/L at the Screening Visit, determined as per central laboratory., Type 1 diabetes mellitus or uncontrolled Type 2 diabetes mellitus with HbA1c > 10.5% (> 91 mmol/mol) at Screening., New York Heart Association functional HF class IV at screening., 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., Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit., Any acute kidney injury within 3 months prior to the Screening Visit, History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone to slow CKD progression, assessed as the effect on change in eGFR ( eGFR estimated glomerular filtration rate) over time.;Secondary Objective: To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone at reducing UACR (urine albumin-creatinine ratio)., To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone at reducing SBP (Systolic blood pressure)., To determine whether baxdrostat/dapagliflozin compared with dapagliflozin alone slows CKD progression and reduces the risk of ESKD (End-stage kidney disease)., To determine whether baxdrostat/dapagliflozin compared with dapagliflozin alone slows the rate of kidney function decline after the hemodynamically-mediated acute effect on GFR (Glomerular Filtration Rate).;Primary end point(s): Change from baseline in eGFR to post treatment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):1. Change from baseline in UACR.;Secondary end point(s):2. Change from baseline in systolic BP (blood pressure).;Secondary end point(s):3. Kidney hierarchical composite endpoint.* *Defined as the most severe outcome of the following: 1. Death; 2. KFRT (chronic dialysis or kidney transplant); 3. Sustained GFR < 15 mL/min/1.73 m2; 4. Sustained GFR decline from baseline of = 57%; 5 Sustained GFR decline from baseline of = 50%; or 6. individual change from baseline to post-treatment eGFR if none of the outcomes occurred.;Secondary end point(s):4. Change in eGFR from following randomisation.