A Phase III Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin on CKD Progression in Participants With CKD and High Blood Pressure.

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Chronic Kidney Disease and Hypertension

Treatments: Drug: Baxdrostat/dapagliflozin; Drug: Dapagliflozin in combination with placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06268873

D6972C00003

2023-506457-38-00 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to measure the efficacy and safety of baxdrostat/dapagliflozin in participants ≥ 18 years of age with CKD and HTN.

This study consists of a screening, a 4-week dapagliflozin run-in period for participants naïve to SGLT2i at baseline; a 24-month double-blind period in which participants will receive either baxdrostat/dapagliflozin or dapagliflozin; and a 6-week open-label period in which all participants will discontinue baxdrostat/placebo and receive dapagliflozin alone.

Site visits will take place at 2-, 4-, 8-, and 16- weeks following randomisation. Thereafter visits will occur approximately every 4 months, until the 24-month visit at which time baxdrostat/placebo will be discontinued. Participants will continue open-label dapagliflozin for another 6-weeks (approximately), where reassessment of GFR will occur for the primary efficacy endpoint.

In the event of premature discontinuation of blinded study intervention, participants will continue in the study and receive open-label dapagliflozin monotherapy, unless the participant meets dapagliflozin specific discontinuation criteria, in which case all study interventions will be discontinued.

Enrollment: 2,500 estimated patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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. Participants with CKD and eGFR ≥ 30 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 at screening and ≥ 120 mmHg 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, potassium must be ≥ 3.0 and ≤ 4.8 mmol/L at the Screening Visit
   • for participants with screening eGFR < 45 mL/min/1.73 m2, potassium must be ≥ 3.0 and ≤ 4.5 mmol/L at the Screening Visit

Exclusion criteria

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

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

3. Serum sodium < 135 mmol/L at the Screening Visit, determined as per central laboratory.

4. Diabetes mellitus:

   (a) T1DM at Screening Visit: (i) For US only: patients with T1DM treated with SGLT2i for at least 4 months, without DKA during that period, and who have experience with ketone monitoring are eligible for inclusion.

   (ii) For Japan only: patients with T1DM treated with dapagliflozin 10 mg for at least 4 months, without DKA during the period of dapagliflozin treatment are eligible for inclusion.

   (b) Uncontrolled T2DM at screening: HbA1C > 10.5% (> 91 mmol/mol).

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,500 participants in 2 patient groups

Baxdrostat/dapagliflozin

Experimental group

Description:

Participants randomised to the baxdrostat/dapagliflozin arm will initially receive a dose of baxdrostat lower dose and dapagliflozin. For participants that meet the up-titration criteria, baxdrostat may be up-titrated to higher dose.

Treatment:

Drug: Baxdrostat/dapagliflozin

Dapagliflozin

Active Comparator group

Description:

Patients will receive one dose of dapagliflozin (active comparator) in combination with placebo matching baxdrostat daily

Treatment:

Drug: Dapagliflozin in combination with placebo