Baxdrostat + Dapagliflozin for Chronic Kidney Disease

Recruiting at 511 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must be taking: ACE inhibitors, ARBs

Must not be taking: Potassium-sparing diuretics

Disqualifiers: Uncontrolled diabetes, Heart failure, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Dapagliflozin for chronic kidney disease?

Research shows that Dapagliflozin can reduce the risk of worsening kidney function and kidney failure in people with chronic kidney disease, whether or not they have type 2 diabetes. In the DAPA-CKD trial, it significantly reduced major kidney-related problems, making it a promising option for slowing down kidney disease progression. ^{1 2 3 4 5}

Is the combination of Baxdrostat and Dapagliflozin safe for humans?

Dapagliflozin, also known as Farxiga or Forxiga, is generally considered safe for humans and is approved to reduce the risk of kidney and heart issues in adults with chronic kidney disease and type 2 diabetes. It has been studied for its safety and tolerability in treating type 2 diabetes, although it is no longer licensed for type 1 diabetes. ^{1 3 5 6 7}

How does the drug Baxdrostat + Dapagliflozin differ from other treatments for chronic kidney disease?

This treatment combines Baxdrostat, a novel drug, with Dapagliflozin, which is already known to reduce the risk of kidney function decline and cardiovascular issues in chronic kidney disease. The combination may offer enhanced benefits by targeting different pathways to slow disease progression. ^{1 4 5 8 9}

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Dapagliflozin (SGLT2 Inhibitor)

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.

Participant Groups

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

Findings from Research

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 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 (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, 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. Belgium pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]

4. Spain pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis. [2023]

9. Australia 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. [2023]