Baxdrostat + Dapagliflozin for Chronic Kidney Disease

Not currently recruiting at 600 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: ACE inhibitors, ARBs

Must not be taking: Potassium-sparing diuretics

Disqualifiers: Uncontrolled diabetes, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs, baxdrostat and dapagliflozin (a medication for type 2 diabetes and heart failure), to determine if they can help people with chronic kidney disease (CKD) and high blood pressure (hypertension) manage their condition better. Participants will receive either both drugs or just dapagliflozin to compare their effectiveness. Those with CKD, moderate kidney function, a history of hypertension, and who are already on blood pressure medication like ACE inhibitors, may be suitable for this trial. The goal is to find a safe and effective way to improve kidney health and control blood pressure. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you have been on a stable and maximum tolerated dose of an ACE inhibitor or an ARB (but not both) for at least 4 weeks before the screening. You must also stop using certain medications like mineralocorticoid receptor antagonists, potassium-sparing diuretics, or potassium binders at least 4 weeks before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using baxdrostat with dapagliflozin is both effective and safe. Studies have found that this combination significantly lowers blood pressure, indicating that the treatment is generally well-tolerated. Some side effects, usually mild, have been reported. For baxdrostat, these may include dizziness or fatigue. The FDA has already approved dapagliflozin for other uses, supporting its safety. Participants should discuss any potential side effects with their doctor, as all medications can have side effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for chronic kidney disease?

Researchers are excited about baxdrostat combined with dapagliflozin for chronic kidney disease because it targets the condition in a novel way. Unlike standard treatments that primarily focus on controlling symptoms or slowing disease progression, baxdrostat works by inhibiting aldosterone synthase. This could potentially lead to better control of blood pressure and kidney protection. Additionally, the combination with dapagliflozin, which is already known for its kidney-protective effects, may enhance overall treatment efficacy, offering a more comprehensive approach to managing chronic kidney disease.

What evidence suggests that this trial's treatments could be effective for chronic kidney disease?

This trial will compare the effects of Dapagliflozin alone with the combination of Baxdrostat and Dapagliflozin for chronic kidney disease. Research has shown that using Baxdrostat with Dapagliflozin may help lower blood pressure in people with difficult-to-control high blood pressure. In one study, Baxdrostat lowered the top number in a blood pressure reading by 15.7 points, which was 9.8 points more than a dummy pill. Dapagliflozin is already known to help people with long-term kidney problems by protecting the kidneys and managing blood sugar levels. Together, these treatments might offer better results for those with kidney issues and high blood pressure. Studies are ongoing to confirm how well and how safely they work together. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with chronic kidney disease (CKD) and high blood pressure. Participants should not have previously used SGLT2 inhibitors, a type of diabetes medication. They must be willing to take the study drugs and visit the site regularly over two years.

Inclusion Criteria

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

I have been on a stable dose of ACE inhibitor or ARB medication for at least 4 weeks.

My blood potassium levels are within the range based on my kidney function test results.

Exclusion Criteria

Systolic blood pressure > 180 mmHg, or DBP > 110 mmHg at 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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

A 4-week dapagliflozin run-in period for participants naïve to SGLT2i at baseline

4 weeks

1 visit (in-person)

Double-blind Treatment

Participants receive either baxdrostat/dapagliflozin or dapagliflozin alone

24 months

Visits at 2, 4, 8, 16 weeks, then every 4 months

Open-label Period

All participants receive open-label dapagliflozin after discontinuing baxdrostat/placebo

6 weeks

1 visit (in-person) for GFR reassessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin

Trial Overview The trial tests if baxdrostat combined with dapagliflozin can slow down CKD progression better than dapagliflozin alone in patients with CKD and hypertension. It's a double-blind study, meaning neither participants nor researchers know who gets which treatment until after the results are collected.

How Is the Trial Designed?

Group I: Baxdrostat/dapagliflozin Experimental Treatment 1 Intervention

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.

Group II: Dapagliflozin Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Dapagliflozin effectively lowers blood sugar levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, with a low risk of hypoglycemia and additional benefits like weight loss and reduced blood pressure.

While it is generally safe, dapagliflozin can increase the risk of genital infections, particularly in women, and its efficacy may be reduced in patients with kidney issues; ongoing trials are investigating its potential cardiovascular and renal protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. Scheen, AJ.[2021]

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

Dapagliflozin (Forxiga) is no longer authorized for the treatment of type 1 diabetes mellitus, indicating a significant change in its regulatory status.

This decision reflects safety concerns or efficacy issues that may have arisen from clinical evaluations or post-marketing surveillance, emphasizing the importance of ongoing drug safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin no longer licensed for type 1 diabetes. [2022]

In the DAPA-CKD trial, dapagliflozin significantly improved long-term outcomes for patients with chronic kidney disease (CKD), allowing them to spend more time in earlier CKD stages (1-3) and less time in advanced stages (4-5) over a 10-year period.

The use of dapagliflozin is projected to prevent approximately 83 deaths and 51 cases of kidney replacement therapy per 1000 patients, while also reducing the rates of hospitalized heart failure and sudden declines in kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis. McEwan, P., Boyce, R., Sanchez, JJG., et al.[2023]

In a study of 54 patients with chronic kidney disease (CKD) treated with dapagliflozin (DAPA), those with a higher baseline proteinuria (UPCR ≥0.5 g/gCr) showed a significant decrease in protein levels after one month, indicating that DAPA can effectively reduce proteinuria in certain patients.

The study found that patients who responded to DAPA with a greater than 30% decrease in UPCR also experienced a more significant initial decline in estimated glomerular filtration rate (eGFR), suggesting a relationship between proteinuria response and kidney function decline in CKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The proteinuria-lowering effects of dapagliflozin are associated with an initial decline in estimated glomerular filtration rate in patients with chronic kidney disease. Murakoshi, M., Kobayashi, T., Kihara, M., et al.[2023]

Dapagliflozin, an SGLT2 inhibitor, is effective in treating type 2 diabetes and has been shown to significantly reduce cardiovascular and major renal events in clinical trials.

In the DAPA-CKD trial, dapagliflozin notably decreased the risk of kidney disease progression in patients with chronic kidney disease, making it a valuable treatment option for both diabetic and non-diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on dapagliflozin for chronic kidney disease. Kelly, MS.[2022]

The fixed-dose combination of dapagliflozin and saxagliptin (QTERN) effectively reduces hemoglobin A1C levels in patients with uncontrolled type 2 diabetes when used alongside metformin, showing a significant difference in A1C reduction compared to other combinations.

QTERN is generally well tolerated, but its use may be limited by cost and modest efficacy in A1C reduction, highlighting the need for further research on its long-term effects on diabetes complications and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin/Saxagliptin Fixed-Dose Tablets: A New Sodium-Glucose Cotransporter 2 and Dipeptidyl Peptidase 4 Combination for the Treatment of Type 2 Diabetes. Coppenrath, VA., Hydery, T.[2022]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06742723

Study Details | NCT06742723 | A Phase III Renal ... The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo ...

2. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D6972C00002

BaxDuo-Pacific The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and ...

3. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/baxdrostat-demonstrated-statistically-significant-clinically-meaningful-reduction-sbp-patients-hard-control-hypertension-baxhtn-phase-iii-trial.html

Baxdrostat demonstrated statistically significant and ... Baxdrostat 2mg lowered systolic blood pressure by 15.7 mmHg (9.8 mmHg placebo-adjusted) from baseline, and was generally well tolerated with ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06268873

NCT06268873 | A Phase III Study to Investigate the ... 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.

5. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D6972C00003

A Phase III Study to Investigate the Efficacy and Safety of ... 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.

6. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/baxdrostat-met-the-primary-endpoint-in-bax24-phase-iii-trial-in-patients-with-resistant-hypertension.html

Baxdrostat met the primary endpoint in Bax24 Phase III trial ... Baxdrostat demonstrated a statistically significant and highly clinically meaningful reduction in 24-hour ambulatory systolic blood pressure ...