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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

7 May 2025 → ongoing

Decision date (initial)

2025-04-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacodynamic, Safety

1. To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of the composite endpoint of ≥ 50% sustained decline in eGFR, kidney failure, HF events, or CV death.

Secondary objectives 4

1. 1. To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of the composite endpoint of ≥ 50% sustained decline in eGFR, kidney failure, or CV death.
2. 2. To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of MACE (CV death, HF events, MI, stroke).
3. 3. To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of CV death
4. 4. To determine whether baxdrostat/dapagliflozin is superior to placebo/dapagliflozin in reducing the risk of all-cause death

Conditions and MedDRA coding

Chronic kidney disease (CKD) and hypertension.

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003559-PIP01-23

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participants of any sex and gender must be ≥ 18 years of age at the time of signing the informed consent.
2. Participants with (a) or (b): a) eGFR 30-59 mL/min/1.73 m² (local or central laboratory value) AND: - UACR ≥ 30 mg/g (3.39 mg/mmol) and < 500 mg/g (56.5 mg/mmol) (central laboratory value), or - UACR ≥ 500 mg/g (56.5 mg/mmol) and ≤ 5000 mg/g (565 mg/mmol) (local or central laboratory value), or - UPCR ≥ 700 mg/g (79 mg/mmol) and ≤ 7000 mg/g (790 mg/mmol) (local laboratory value only). (b) eGFR 60-75 mL/min/1.73 m² (local or central laboratory value) AND: - UACR ≥ 500 mg/g (56.5 mg/mmol) ) and ≤ 5000 mg/g (565 mg/mmol) (local or central laboratory value), or - UPCR ≥ 700 mg/g (79 mg/mmol) and ≤ 7000 mg/g (790 mg/mmol) (local laboratory value only)
3. Participants with history of HTN and a SBP ≥ 130 mmHg (the most recent value within 4 weeks prior to screening or at Screening visit) and ≥ 120 mmHg at the randomisation visit
4. Stable and maximum tolerated dose of an ACEi or an ARB (not both) for at least 4 weeks prior to Screening Visit.
5. Participants with: a) Serum or plasma potassium ≥ 3.0 and ≤ 4.8 mmol/L if eGFR ≥ 45 mL/min/1.73 m2 (local or central laboratory values). b) Serum or plasma potassium ≥ 3.0 and ≤ 4.5 mmol/L if eGFR < 45 mL/min/1.73 m2 (local or central laboratory values).

Exclusion criteria 12

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 at 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. Participants with T1DM will be excluded, except: a) 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. b)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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Time to the first occurrence of any of the components of the composite of: • Kidney disease progression • ≥ 50% sustained decline in eGFR • 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) • CV events • HF with or without hopsitalization • CV death

Secondary endpoints 4

1. 1. Time to the first occurrence of any of the components of the composite of: • ≥ 50% sustained decline in eGFR • 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) • CV death
2. 2. Time to the first occurrence of any of the components of the composite of: • CV death • HF with or without hospitalization • MI • stroke
3. 3. CV death
4. 4. Time to all-cause death

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

Clinical Study Information Center

Locations

15 EU/EEA countries · 235 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 165 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications