A Phase III, Randomised, Double-Blind, Active-controlled Study to Assess the Efficacy, Safety and Tolerability of Baxdrostat in Combination With Dapagliflozin Compared With Dapagliflozin Alone on Chronic Kidney Disease (CKD) Progression in Participants With CKD and High Blood Pressure

JRCT ID: jRCT2031240043

Registered date:23/04/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Chronic Kidney Disease and Hypertension
• Date of first enrollment: 31/05/2024
• Target sample size: 2500
• Countries of recruitment: Argentina,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,Peru,Japan,United States,Japan,Belguim,Japan,Bulgaria,Japan,Czech Republic,Japan,Denmark,Japan,France,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Netherlands,Japan,Poland,Japan,Romania,Japan,Serbia,Japan,Slovakia,Japan,Spain,Japan,Sweden,Japan,Ukraine,Japan,United Kingdom,Japan,China,Japan,Australia,Japan,India,Japan,Malaysia,Japan,Philippine,Japan
• Study type: Interventional

Intervention(s)

Run-in Period: Participants who are not on SGLT2i at screening will receive a run-in intervention with dapagliflozin.

Double-blind period: Participantsl receive a baxdrostat and dapagliflozin or placebo matching baxdrostat and dapagliflozin.

Open-label period: Participantsl receive a dapagliflozin.

Outcome(s)

Primary Outcome

To determine whether baxdrostat/dapagliflozin is superior to dapagliflozin alone to slow CKD progression, assessed as the effect on change in eGFR over time. [ Time Frame: Baseline - 2 years + 6 weeks ]
Change from baseline in eGFR to post treatment.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Participants of any sex and gender must be 18 years old or more, or older, at the time of signing the informed consent.

2. Participants with CKD and eGFR 30 or more and < 90 mL/min/1.73 m2 at screening

3. Urine albumin creatinine ratio > 200 mg/g (22.6 mg/mmol) and < 5000 mg/g (565 mg/mmol) at screening

4. Participants with history of HTN and a SBP 130 mmHg or more at screening and 120 mmHg or more at the randomisation visit

5. Stable and maximum 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:

- for participants with screening eGFR 45 mL/min/1.73 m2 or more, potassium must be 3.5 or more and 4.8 mmol/L or less at the Screening Visit

- for participants with screening eGFR < 45 mL/min/1.73 m2, potassium must be 3.5 or more and 4.5 mmol/L or less at the Screening Visit

Exclude criteria

1. Systolic blood pressure > 180 mmHg, or DBP > 110 mmHg at screening.

2. Known hyperkalaemia, defined as potassium of 5.5 mmol/L or more within 3 months at screening.

3. Serum sodium < 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 > 10.5% (> 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. Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit.

8. Any acute kidney injury within 3 months prior to the Screening Visit

9. History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).

10. History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2 inhibitor (eg, empagliflozin) or ASI.

11. Any clinical condition requiring systemic immunosuppression therapy other than stable maintenance therapy for at least 3 months prior to Visit 1.

12. 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.

Related Information

• Primary Sponsor: Ageishi Yuji
• Secondary ID(s): NCT06268873