A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure

Phase 3

Not yet recruiting

• Conditions: Chronic Kidney Disease and Hypertension
• Interventions: Drug: Baxdrostat/dapagliflozin; Drug: Placebo/dapagliflozin

• Registration Number: NCT06742723
• Lead Sponsor: AstraZeneca

Brief Summary

International, Multicenter, Double-Blind, Placebo-Controlled and Event-driven study to assess efficacy, safety and Tolerability of Baxdrostat in combination with Dapagliflozin on renal outcomes and cardiovascular mortality in participants with chronic kidney disease and high blood pressure

Detailed Description

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of \> 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN.
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-16
• Study First Submitted QC: 2024-12-16
• Last Update Submitted: 2024-12-16
• Study First Posted: 2024-12-19
• Last Update Posted: 2024-12-19
• Study Start: 2025-03-03
• Primary Completion: 2030-04-18
• Study Completion: 2030-04-18

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 5000

Inclusion Criteria

1. Participants of any sex and gender must be ≥ 18 years of age at the time of signing the informed consent.

2. Participants with:

   1. eGFR ≥ 30 and < 60 mL/min/1.73 m2 (local or central laboratory values) AND UACR ≥ 30 mg/g (3.39 mg/mmol) and < 500 mg/g (56.5 mg/mmol) (central laboratory values only), or
   2. eGFR ≥ 30 and ≤ 75 mL/min/1.73 m2 (local or central laboratory values) AND UACR ≥ 500 mg/g (56.5 mg/mmol) and ≤ 5000 mg/g (565 mg/mmol) or UPCR ≥ 700 mg/g (79 mg/mmol) and ≤ 7000 mg/g (790 mg/mmol) (local or central laboratory values).

3. [obsolete]

4. Participants with history of HTN and a SBP ≥ 130 mmHg (the most recent value within 4 weeks prior to screening or at the Screening Visit) and ≥ 120 mmHg at the Randomisation Visit.

5. Stable and maximum tolerated dose of an ACEi or an ARB (not both) for at least 4 weeks prior to Screening Visit.

6. Participants with:

   1. Serum or plasma potassium ≥ 3.0 and ≤ 4.8 mmol/L if eGFR ≥ 45 mL/min/1.73 m2 (local or central laboratory values).
   2. Serum or plasma potassium ≥ 3.0 and ≤ 4.5 mmol/L if eGFR < 45 mL/min/1.73 m2 (local or central laboratory values).

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Exclusion Criteria

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

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

3. Serum sodium < 135 mmol/L (central or local laboratory values obtained within 4 weeks prior to screening or at the Screening Visit).

4. T1DM:

5. 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.

6. 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.

   5 Uncontrolled T2DM with HbA1c > 10.5% (> 91 mmol/mol) (central or local laboratory values obtained within 3 months prior to screening or at the Screening Visit).

   6 New York Heart Association functional HF class IV at screening.

   7 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.

   8 Documented history of adrenal insufficiency.

   9 Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit.

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

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

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Baxdrostat/dapagliflozin	Baxdrostat/dapagliflozin	Participants randomised to the baxdrostat/dapagliflozin arm will initially receive a lower dose of baxdrostat and standard dose dapagliflozin. For participants that meet the up-titration criteria, baxdrostat may be up-titrated to higher dose.
Placebo/dapagliflozin	Placebo/dapagliflozin	Patients will receive one dose of dapagliflozin comparator in combination with matching placebo daily.

Primary Outcome Measures

Name	Time	Method
To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of the composite endpoint of ≥ 50% sustained decline in eGFR (estimated glomerular filtration rate)	Up to 41 months	Time to the first occurrence of any of the components of the composite of ≥ 50% sustained decline in eGFR (estimated glomerular filtration rate).
To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of the composite endpoint of kidney failure	Up to 41 months	Time to the first occurrence of any of the components of the composite of: • Onset of kidney failure: * Sustained eGFR \< 15 mL/min/1.73 m2 or; * Chronic dialysis treatment or; * Receiving a kidney transplant or; * Death with a renal primary cause (death due to kidney failure when dialysis is not given)
To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of the composite endpoint of CV (cardiovascular) death.	Up to 41 months	Time to the first occurrence of any of the components of the composite of CV (cardiovascular) death

Secondary Outcome Measures

Name	Time	Method
To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin at reducing UACR (urine albumin-creatinine ratio).	Baseline- 16 weeks	Change from baseline in UACR (urine albumin-creatinine ratio).
To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin at reducing SBP (systolic blood pressure).	Baseline- 16 weeks	Change from baseline in mean systolic BP (blood pressure).
To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of MACE (Major Adverse Cardiac Events).	Up to 41 months	Time to the first occurrence of any of the components of the composite of: CV (cardiovascular) death, HF (heart failure) with and without hospitalization, Myocardial Infraction, Stroke
To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of CV death.	Up to 41 months	Time to CV death
To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of all-cause death.	Up to 41 months	Time to death

Trial Locations

Locations (1)

Research Site; 🇻🇳 Ho Chi Minh, Vietnam