Baxdrostat + Dapagliflozin for Chronic Kidney Disease and High Blood Pressure

(BaxDuo-Pacific Trial)

Recruiting at 531 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: ACEi, ARB

Disqualifiers: T1DM, Uncontrolled T2DM, Heart failure, others

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 41 months

5000 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on a stable and maximum tolerated dose of an ACE inhibitor or an ARB for at least 4 weeks before the screening visit.

What data supports the effectiveness of the drug combination Baxdrostat + Dapagliflozin for chronic kidney disease and high blood pressure?

Research shows that Dapagliflozin (Farxiga) is effective in reducing the risk of worsening kidney function and heart-related issues in people with chronic kidney disease. Additionally, it has been shown to lower blood pressure, which can be beneficial for patients with high blood pressure. ^{1 2 3 4 5}

What makes the drug combination of Baxdrostat and Dapagliflozin unique for treating chronic kidney disease and high blood pressure?

This drug combination is unique because Dapagliflozin is already approved to reduce the risk of kidney function decline and heart-related issues in chronic kidney disease, while Baxdrostat may offer additional benefits by targeting different mechanisms, potentially enhancing the overall treatment effect. ^{1 3 4 6 7}

Eligibility Criteria

This trial is for people with chronic kidney disease and high blood pressure. Participants should not have other serious health conditions that could interfere with the study or be at risk of rapid progression to kidney failure.

Inclusion Criteria

I am not on any new immunosuppression drugs except for stable maintenance ones.

My kidney function is moderately reduced, and I have protein in my urine.

I have a documented history of adrenal insufficiency.

Exclusion Criteria

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

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

I have not had dialysis in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Period

Participants untreated with SGLT2i at screening undergo a 4-week dapagliflozin run-in period

4 weeks

1 visit (in-person)

Treatment

Participants receive either baxdrostat/dapagliflozin or placebo/dapagliflozin in a double-blind manner

Up to 41 months

Visits at 2, 4, 8, 16, 34, and 52 weeks, then every 4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Baxdrostat
• Dapagliflozin

Trial Overview The study tests Baxdrostat combined with Dapagliflozin against a placebo/dapagliflozin combo. It's international, multicenter, double-blind (meaning neither doctors nor patients know who gets what), and focuses on how well kidneys work and heart health.

Participant Groups

Group I: Baxdrostat/dapagliflozin Experimental Treatment 1 Intervention

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.

Group II: Placebo/dapagliflozin Placebo Group 1 Intervention

Patients will receive one dose of dapagliflozin comparator in combination with matching placebo 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]

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]

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]

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 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]

References

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

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

2. 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]

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

5. Belgium pubmed.ncbi.nlm.nih.gov

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

6. Ireland pubmed.ncbi.nlm.nih.gov

Activation of farnesoid X receptor downregulates visfatin and attenuates diabetic nephropathy. [2018]

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

Quételet (body mass) index and effects of dapagliflozin in chronic kidney disease. [2022]