Baxdrostat for High Blood Pressure

(BaxHTN Trial)

No longer recruiting at 300 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Diuretics, Antihypertensives

Disqualifiers: Heart failure, Atrial fibrillation, 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: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests baxdrostat, a medication designed to lower high blood pressure in individuals whose current medications are insufficient. Participants will take either 1 mg or 2 mg of baxdrostat or a placebo (a pill with no active medication) once daily. The trial aims to determine if baxdrostat can safely reduce systolic blood pressure, the pressure when the heart beats. Individuals with high blood pressure who are already on two or more medications, including a diuretic (a water pill), but still struggle to control their blood pressure might be suitable for this trial. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for high blood pressure.

Do I need to stop my current medications for this trial?

No, you do not need to stop your current medications. The trial requires participants to have a stable regimen of 2 or more antihypertensive medications, including a diuretic, at the maximum tolerated dose.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial requires participants to continue their stable regimen of antihypertensive medications, including a diuretic.

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

Research has shown that baxdrostat, the treatment under study for high blood pressure, has undergone safety testing in earlier studies. These studies examined how patients with hard-to-treat high blood pressure responded to baxdrostat.

In one study, baxdrostat effectively lowered blood pressure in these patients and was generally well-tolerated, with most participants not experiencing serious side effects. While some had mild side effects, no major safety concerns arose.

Another study found that baxdrostat significantly reduced blood pressure without causing major issues, suggesting it is generally safe, especially for those unresponsive to other treatments.

These findings indicate baxdrostat's safety for individuals considering participation in a clinical trial for this medication. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for high blood pressure?

Unlike the standard treatments for high blood pressure, which typically include ACE inhibitors, beta-blockers, or calcium channel blockers, Baxdrostat offers a novel approach by targeting aldosterone synthase, an enzyme involved in hormone production that regulates blood pressure. This unique mechanism of action could potentially address cases where traditional medications are less effective. Researchers are excited about Baxdrostat because it represents a new class of antihypertensive agents, offering hope for those whose high blood pressure remains uncontrolled with current options.

What evidence suggests that this trial's treatments could be effective for high blood pressure?

Research has shown that baxdrostat helps lower high blood pressure. One study significantly reduced 24-hour systolic blood pressure, an important measure of heart health. This trial will evaluate different doses of baxdrostat, including 1 mg and 2 mg, as separate treatment arms. In previous research, patients taking 2 mg of baxdrostat saw their systolic blood pressure drop by 15.7 mmHg from the start, marking a significant improvement. Additionally, about 40% of patients achieved a systolic blood pressure below 130 mmHg, a common goal for those with high blood pressure. Overall, baxdrostat has proven effective in lowering blood pressure in people whose hypertension is difficult to manage. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with high blood pressure not controlled by at least two medications, including a diuretic. Participants must have certain levels of potassium and kidney function. It's not for those with extremely high blood pressure or secondary causes like thyroid issues or specific heart conditions.

Inclusion Criteria

Your blood pressure while sitting is between 140 and 170 mmHg during the screening.

Your blood pressure is higher than 135 mmHg when taken in the doctor's office.

Meet at least one of these two requirements:

Exclusion Criteria

Your blood test shows that your sodium level is below 135 mmol/L.

My heart failure is severe, limiting my ability to carry out physical activity.

I have ongoing irregular heartbeats.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1 or 2 mg baxdrostat or placebo once daily to assess the reduction of systolic blood pressure

12 weeks

Regular visits for blood pressure monitoring

Randomised Withdrawal

Participants undergo randomised withdrawal to assess the effect of baxdrostat versus placebo on blood pressure

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 54 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Baxdrostat
• Placebo

Trial Overview The study tests Baxdrostat (1 or 2 mg daily) against a placebo in reducing systolic blood pressure. It's a Phase III trial where participants are randomly assigned to either the drug or placebo group without knowing which one they're receiving.

How Is the Trial Designed?

Group I: 2 mg baxdrostat Experimental Treatment 1 Intervention

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

Group II: 1 mg baxdrostat Experimental Treatment 1 Intervention

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

Group III: 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

Published Research Related to This Trial

The study identified four steroidal derivatives that effectively inhibit the 5alpha-reductase enzyme, with compound 10b being the most potent, showing an IC(50) value of 4.9 nM, which indicates strong potential for treating conditions related to dihydrotestosterone.

In vivo tests demonstrated that steroid 10b significantly reduced prostate gland weight in gonadectomized hamsters treated with testosterone, similar to the effects of the established medication finasteride, suggesting its efficacy as a therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatic esters of progesterone as 5alpha-reductase and prostate growth inhibitors. Bratoeff, E., Segura, T., Recillas, S., et al.[2013]

The incidence of acute urinary retention (AUR) in men with benign prostatic hyperplasia (BPH) varies significantly across treatments, with rates during active treatment being 0.9 to 5.2% for placebo, 0 to 1.2% for alpha-blockers, and 0.3 to 1.2% for finasteride, indicating that alpha-blockers may have a lower risk of AUR compared to placebo and finasteride.

Comparing AUR rates across different studies without considering factors like spontaneous versus precipitated AUR, patient follow-up, and prostate volume can lead to misleading conclusions about the safety and efficacy of treatments for BPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of acute urinary retention in BPH treatment trials: importance of patient follow-up after discontinuation and case definitions. Roehrborn, CG.[2019]

In a long-term study of 186 men with benign prostatic hyperplasia (BPH), finasteride 5 mg effectively reduced prostate volume by 22.7% and improved urinary symptoms over 5 years, demonstrating sustained efficacy.

Finasteride was well tolerated throughout the study, with no significant increase in sexual side effects, indicating its safety for long-term use in treating BPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group. Hudson, PB., Boake, R., Trachtenberg, J., et al.[2022]

A systematic review of dietary supplements for treating benign prostatic hyperplasia (BPH) found that while Serenoa repens showed no specific effects on BPH symptoms, β-sitosterol, Pygeum africannum, and Cernilton demonstrated significant improvements in symptoms and urinary flow.

All reviewed supplements had mild and infrequent adverse effects, indicating they are generally safe for use, but the evidence for β-sitosterol, Pygeum africannum, and Cernilton is outdated and requires further review.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary supplements for benign prostatic hyperplasia: an overview of systematic reviews. Kim, TH., Lim, HJ., Kim, MS., et al.[2015]

Both the LIFE trial and SCOPE study showed that losartan and candesartan, respectively, significantly reduced the risk of stroke compared to placebo, with relative risks of 0.53 and 0.56, indicating a strong efficacy beyond just lowering blood pressure.

Neither trial demonstrated a statistically significant benefit in reducing coronary heart disease events, suggesting that while these medications are effective for stroke prevention, their impact on heart disease outcomes remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A putative placebo comparison of the SCOPE and LIFE trials. Meredith, PA., Murray, LS., McMurray, JJ.[2007]

Inhibitors STX2171 and STX2624 selectively target 17beta-HSD3, which is over-expressed in prostate cancer, showing potential as treatments for hormone-dependent prostate cancer with low toxicity and non-androgenic properties.

These compounds effectively inhibited the growth of prostate cancer cells stimulated by androstenedione in vitro and reduced tumor growth in an in vivo model, indicating their efficacy in potentially treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of hormone-dependent prostate cancer models for the evaluation of inhibitors of 17beta-hydroxysteroid dehydrogenase type 3. Day, JM., Tutill, HJ., Foster, PA., et al.[2009]

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 30-month study involving 2,071 elderly patients with isolated systolic hypertension, those receiving active treatment showed significantly lower blood pressure compared to the placebo group starting from the third month (P < 0.05).

The treatment was well-tolerated with mild side effects, and participant compliance was high, with 97% of the active treatment group and 96% of the placebo group adhering to their medication regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Systolic hypertension in the elderly: Chinese trial (syst-China). Interim report]. [2013]

ACP-105 is a newly discovered nonsteroidal selective androgen receptor modulator (SARM) that acts as a partial agonist to testosterone, showing promise for improving anabolic effects in a 2-week study with castrated male rats.

The research also identified potent antiandrogens, including one compound that effectively antagonizes the AR T877A mutant, which is associated with prostate cancer, suggesting potential therapeutic applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators. Schlienger, N., Lund, BW., Pawlas, J., et al.[2013]

The study identified a specific derivative, 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3β-yl-cyclohexanecarboxylate, as a potent inhibitor of the 5α-reductase 2 enzyme with an IC50 of 29nM, which is significant for treating conditions like benign prostatic hyperplasia.

In vivo tests on castrated hamsters showed that these derivatives effectively reduced the weight and size of androgen-dependent glands without toxicity, while one derivative also demonstrated high cytotoxic activity against various cancer cell lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of new derivatives of 21-imidazolyl-16-dehydropregnenolone as inhibitors of 5α-reductase 2 and with cytotoxic activity in cancer cells. Silva-Ortiz, AV., Bratoeff, E., Ramírez-Apan, T., et al.[2017]

Epristeride demonstrated a high total efficacy rate of 81.29% in treating benign prostatic hyperplasia (BPH) among 141 patients over a 120-day period.

The treatment was generally safe, with only a few mild adverse reactions reported, and only 1.44% of patients discontinued due to side effects, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clinical efficacy of epristeride in the treatment of benign prostatic hyperplasia]. Ju, XB., Wu, HF., Hua, LX., et al.[2014]

The compound (4R)-5,10-seco-19-norpregna-4,5-diene-3,10,20-trione (II) effectively blocked the androgenic effects of testosterone in female hamsters, preventing the enlargement and pigmentation of flank organs typically induced by testosterone treatment.

This suggests that compound II could serve as a promising topical anti-androgen by inhibiting the formation of active androgen metabolites, indicating its potential therapeutic use in conditions related to excessive androgen activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of testosterone 5 alpha-reductase by and antiandrogenicity of allenic 3-keto-5,10-secosteroids. Voigt, W., Castro, A., Covey, DF., et al.[2019]

Saw Palmetto and Cernitin were effective in reducing prostate size in rats with androgen-induced prostatic enlargement, demonstrating their potential as safer alternatives to pharmaceuticals like finasteride.

Both nutraceuticals influenced androgen metabolism, leading to prostate size reductions comparable to those achieved with conventional treatments, while also showing a decrease in body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Saw Palmetto (extract and whole berry) and Cernitin on prostate growth in rats. Talpur, N., Echard, B., Bagchi, D., et al.[2019]

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]

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]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7618089/

Baxdrostat Efficacy and Safety in Uncontrolled and Resistant ... Baxdrostat added to background therapy resulted in a reduction in seated-SBP at 12 weeks compared with placebo in patients with uncontrolled or ...

3. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/Baxdrostat-demonstrated-statistically-significant-and-clinically-meaningful-reduction-in-systolic-blood-pressure-in-patients-with-hard-to-control-hypertension-in-the-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. nature.com nature.com/articles/s41440-025-02415-5

Baxdrostat and the future of aldosterone-targeted therapy Approximately 40% of patients achieved a systolic blood pressure below 130 mmHg. These results indicate that direct inhibition of aldosterone ...

5. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2507109

Efficacy and Safety of Baxdrostat in Uncontrolled and ... In several studies, baxdrostat, an aldosterone synthase inhibitor, reduced the seated systolic blood pressure of patients with uncontrolled or ...

6. escardio.org escardio.org/The-ESC/Press-Office/Press-releases/Blood-pressure-reductions-with-baxdrostat-in-patients-with-uncontrolled-or-resistant-hypertension

Blood-pressure reductions with baxdrostat in patients ... The BaxHTN trial investigated the efficacy and safety of the selective aldosterone synthase inhibitor, baxdrostat, in patients with uncontrolled ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06034743

NCT06034743 | A Study to Investigate the Efficacy and ... This is a Phase III, multicentre, randomised, double-blinded, placebo-controlled, parallel group study to evaluate the safety, tolerability and effect of 1 ...