Baxdrostat for High Blood Pressure

(Bax24 Trial)

Recruiting at 82 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: Antihypertensives, Diuretics

Disqualifiers: Renal artery stenosis, Hyperthyroidism, Hypothyroidism, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and the effect of 2 mg Baxdrostat vs. placebo, administered QD orally, on the reduction of SBP, measured by average 24-hour ABPM in 212 participants with rHTN (defined as seated SBP ≥ 140 mmHg at Screening and mean ambulatory SBP ≥ 130 mmHg at baseline, despite a stable regimen of ≥ 3 antihypertensive agents, one of which is a diuretic).

Will I have to stop taking my current medications?

The trial requires participants to stay on their current medications, as they must have a stable regimen of at least three antihypertensive medications, including a diuretic, for at least four weeks before joining the study.

What data supports the effectiveness of the drug Baxdrostat for high blood pressure?

Baxdrostat, a drug that blocks aldosterone production, showed promising results in a phase 2 trial for patients with treatment-resistant high blood pressure, although another trial did not find it more effective than a placebo. It has been shown to significantly reduce aldosterone levels, which is linked to high blood pressure, and is considered safe and well-tolerated in healthy volunteers. ^{1 2 3 4 5}

What makes the drug Baxdrostat unique for treating high blood pressure?

Baxdrostat is unique because it is a selective aldosterone synthase inhibitor, which means it specifically targets and reduces aldosterone levels (a hormone that can increase blood pressure) without affecting cortisol levels. This makes it different from other blood pressure medications that may not target aldosterone as directly. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for adults with resistant hypertension, meaning their blood pressure remains high despite taking at least three different blood pressure medications, including a diuretic. They must have specific levels of kidney function and potassium in their blood to join.

Inclusion Criteria

I am 18 years old or older.

Serum potassium (K+) level ≥ 3.5 and < 5.0 mmol/L at Screening, determined as per central laboratory

My average walking blood pressure is 130 mmHg or higher.

Exclusion Criteria

Serum sodium level < 135 mmol/L at Screening, as per central laboratory

Mean seated DBP on AOBPM ≥ 110 mmHg at Screening

I have ongoing irregular heartbeats.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 mg Baxdrostat or placebo orally once daily to assess the effect on ambulatory blood pressure

12 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Baxdrostat (Other)

Trial Overview The study tests Baxdrostat's ability to lower systolic blood pressure compared to a placebo. Participants will be randomly assigned to receive either the drug or placebo once daily, and their 24-hour ambulatory blood pressure will be monitored.

Participant Groups

Group I: 2 mg baxdrostat Experimental Treatment 1 Intervention

2 mg baxdrostat administered orally, once daily (QD).

Group II: Placebo Placebo Group 1 Intervention

Placebo administered orally, once daily (QD)

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

Baxdrostat (CIN-107) is a selective aldosterone synthase inhibitor being tested as a treatment for drug-resistant hypertension, which is linked to serious cardiovascular issues.

While a phase 2 trial (BrigHTN) showed promising efficacy results, the HALO trial found no significant blood pressure-lowering effect of baxdrostat compared to placebo, indicating the need for further studies to assess its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baxdrostat: An Aldosterone Synthase Inhibitor for the Treatment of Systemic Hypertension. Dey, S., Frishman, WH., Aronow, WS.[2023]

Baxdrostat, a selective aldosterone synthase inhibitor, was found to be safe and well-tolerated in a study of 54 healthy volunteers, with no serious adverse events reported and only mild side effects observed.

The study demonstrated that baxdrostat effectively reduced plasma aldosterone levels by 51 to 73% after 10 days of treatment at doses of 1.5 mg or higher, while having no significant impact on cortisol levels, indicating its selective action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. Freeman, MW., Bond, M., Murphy, B., et al.[2023]

In a study involving 27 healthy volunteers, the co-administration of baxdrostat with metformin was found to be safe, with no serious adverse events or significant increases in side effects, indicating good tolerance of the combination.

Baxdrostat did not significantly alter the plasma levels or renal clearance of metformin, suggesting that diabetic patients with hypertension can take both medications without needing to adjust the metformin dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects. Freeman, MW., Bond, M., Murphy, B., et al.[2023]

Baxdrostat, an aldosterone synthase inhibitor, shows promise in effectively managing systemic hypertension (HTN) by potentially overcoming the limitations of traditional treatments that often fail to control blood pressure adequately.

The mechanism of baxdrostat may enhance sodium and blood pressure regulation while reducing oxidative stress and improving endothelial function, which could lead to better cardiovascular outcomes for patients with resistant HTN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldosterone Synthase Inhibitors and Dietary Interventions: A Combined Novel Approach for Prevention and Treatment of Cardiovascular Disease. Awosika, A., Khan, A., Adabanya, U., et al.[2023]

Aldosterone synthase inhibitors (ASI), particularly Baxdrostat, are a promising new class of medications that target resistant hypertension by reducing aldosterone production, which is crucial for blood pressure regulation.

Baxdrostat is currently in phase 3 trials and has shown efficacy in both animal and human studies, indicating its potential to effectively manage uncontrolled hypertension and related conditions like chronic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baxdrostat: A Novel Aldosterone Synthase Inhibitor for Treatment Resistant Hypertension. Dogra, S., Shah, S., Gitzel, L., et al.[2023]

Compound 7aa is a highly potent and selective inhibitor of CYP11B1, showing an IC50 of 9 nM, which is comparable to the existing drug osilodrostat, but with 1500-fold greater selectivity over CYP11B2.

In animal studies, compound 7aa effectively reduced plasma cortisol levels without affecting aldosterone production and showed no inhibition of other important enzymes, indicating a favorable safety profile for further development as a therapeutic option for diseases caused by excessive cortisol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, Synthesis, and Biological Evaluations of Pyridyl 4,5,6,7-Tetrahydro-4,7-Methanobenzo[d]isoxazoles as Potent and Selective Inhibitors of 11&#946;-Hydroxylase. Yin, L., Pan, Y., Xue, Y., et al.[2022]

References

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

Baxdrostat: An Aldosterone Synthase Inhibitor for the Treatment of Systemic Hypertension. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects. [2023]

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

Aldosterone Synthase Inhibitors and Dietary Interventions: A Combined Novel Approach for Prevention and Treatment of Cardiovascular Disease. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Baxdrostat: A Novel Aldosterone Synthase Inhibitor for Treatment Resistant Hypertension. [2023]

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

Design, Synthesis, and Biological Evaluations of Pyridyl 4,5,6,7-Tetrahydro-4,7-Methanobenzo[d]isoxazoles as Potent and Selective Inhibitors of 11&#946;-Hydroxylase. [2022]