Baxdrostat for High Blood Pressure

(BaxHTN Trial)

Recruiting at 246 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

796 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests Baxdrostat, a pill taken regularly, in adults with high blood pressure that isn't controlled by their current medications. Baxdrostat works by lowering the force of blood against artery walls.

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.

What data supports the idea that Baxdrostat for High Blood Pressure is an effective drug?

The available research shows mixed results for Baxdrostat's effectiveness in treating high blood pressure. The BrigHTN trial showed promising results, suggesting that Baxdrostat could be effective for patients with treatment-resistant hypertension. However, the HALO trial did not find any significant blood pressure-lowering benefit compared to a placebo. While Baxdrostat has been shown to safely reduce aldosterone levels, which is linked to high blood pressure, more studies are needed to confirm its effectiveness as a treatment for high blood pressure. ^{1 2 3 4 5}

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 safely reduce aldosterone levels, which are linked to high blood pressure, in healthy volunteers. ^{1 2 3 4 5}

What safety data is available for Baxdrostat in treating high blood pressure?

The provided research does not contain any safety data for Baxdrostat or its other names (CIN-107, Placebo, Control, Dummy Treatment) in the context of high blood pressure. The studies focus on treatments for benign prostatic hyperplasia and do not mention Baxdrostat or related treatments for high blood pressure. ^{6 7 8 9 10}

Is the drug Baxdrostat a promising treatment for high blood pressure?

The provided research articles do not directly discuss Baxdrostat or its effects on high blood pressure. Therefore, based on the given information, we cannot determine if Baxdrostat is a promising treatment for high blood pressure. ^{11 12 13 14 15}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. 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]

2. China pubmed.ncbi.nlm.nih.gov

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

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

A putative placebo comparison of the SCOPE and LIFE trials. [2007]

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

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

6. China pubmed.ncbi.nlm.nih.gov

[The clinical efficacy of epristeride in the treatment of benign prostatic hyperplasia]. [2014]

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

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

8. United States 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. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Dietary supplements for benign prostatic hyperplasia: an overview of systematic reviews. [2015]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of Saw Palmetto (extract and whole berry) and Cernitin on prostate growth in rats. [2019]

11. Denmark pubmed.ncbi.nlm.nih.gov

Inhibition of testosterone 5 alpha-reductase by and antiandrogenicity of allenic 3-keto-5,10-secosteroids. [2019]

12. England 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. [2017]

13. England pubmed.ncbi.nlm.nih.gov

Aromatic esters of progesterone as 5alpha-reductase and prostate growth inhibitors. [2013]

14. Ireland pubmed.ncbi.nlm.nih.gov

Development of hormone-dependent prostate cancer models for the evaluation of inhibitors of 17beta-hydroxysteroid dehydrogenase type 3. [2009]

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

Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators. [2013]