Baxdrostat for High Blood Pressure
(BaxHTN Trial)
Recruiting in Palo Alto (17 mi)
+246 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: AstraZeneca
Pivotal Trial (Near Approval)
Prior Safety Data
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.
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.
12345What 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.
678910Is 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.
1112131415Eligibility 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.
I am 18 years old or older.
+6 more
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.
+3 more
Participant Groups
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.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: 2 mg baxdrostatExperimental Treatment1 Intervention
2 mg baxdrostat administered orally, once daily (QD).
Group II: 1 mg baxdrostatExperimental Treatment1 Intervention
1 mg baxdrostat administered orally, once daily (QD).
Group III: PlaceboPlacebo Group1 Intervention
Placebo administered orally, once daily (QD).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteBirmingham, AL
Research SiteMarkham, Canada
Research SiteNewmarket, Canada
Research SiteMemphis, TN
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
References
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]Baxdrostat is a selective inhibitor of aldosterone synthase designed for the treatment of disorders associated with elevated aldosterone. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of multiple ascending doses of baxdrostat in healthy volunteers. Subjects were randomized to receive oral baxdrostat (0.5, 1.5, 2.5, or 5.0 mg) or placebo once daily for 10 days and were placed on either a low-salt or normal-salt diet for the duration of the study. Blood samples were collected before and after dosing on days 1 and 10 to characterize pharmacokinetics and pharmacodynamics. Safety was assessed by adverse events, physical examinations, electrocardiograms, orthostatic vital signs, and clinical laboratory evaluations. Fifty-four subjects completed the study. There were no deaths or serious adverse events, and all treatment-emergent adverse events in subjects receiving baxdrostat were mild in severity. Plasma levels of baxdrostat increased proportionally with ascending doses, with peak concentrations observed within 4 h after dosing and a mean half-life of 26 to 31 h. A dose-dependent reduction of plasma aldosterone occurred with baxdrostat doses ≥1.5 mg, regardless of diet. Decreases in plasma aldosterone were sustained, with levels reduced by approximately 51 to 73% on day 10. Baxdrostat had no meaningful impact on plasma cortisol levels and resulted in mild dose-dependent decreases in plasma sodium levels and increases in potassium levels. Baxdrostat was safe and well tolerated with a half-life that supports once-daily dosing. The dose-dependent reduction in plasma aldosterone and lack of effect on cortisol demonstrate the selective blockade of aldosterone synthase.
[Systolic hypertension in the elderly: Chinese trial (syst-China). Interim report]. [2013]Two thousand and seventy-one elderly isolated systolic hypertensive patients entered the multicenter, randomized, double-blind, placebo-controlled clinical trial (997 in the active treatment group and 1,074 in the placebo). The differences of age, height, weight, sex constituent and baseline blood pressure between active treatment and placebo groups yielded no significances. In the 30-month follow-up period, the systolic and diastolic blood pressure in the active treatment were lower than the placebo group (P
A putative placebo comparison of the SCOPE and LIFE trials. [2007]The Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial and the Study on Cognition and Prognosis in the Elderly (SCOPE) superficially produced comparable outcomes, with effects on stroke greater than those anticipated from blood pressure (BP) lowering alone. This, however, ignores important features of both studies. It ignores firstly the disparate comparator agents - atenolol in LIFE and predominantly hydrochlorthiazide in SCOPE, secondly the small, but potentially important BP differential between the treatment arms in SCOPE and finally the small, statistically non-significant increase in coronary heart disease (CHD) in both trials. This analysis compares the major cardiovascular outcomes in these trials with reference to placebo. Two alternative reference populations were employed to calculate the imputed placebo, firstly the MRC Trial in Elderly Hypertensives and secondly a meta-analysis of trials in the elderly, which included comparisons between diuretic- and b-blocker-based regimens. Overall, the choice of 'comparator placebo' did not substantially influence the derived results. Accounting for BP differences and based on the meta-analysis, both trials demonstrated statistically significant reductions in fatal/non-fatal stroke compared with placebo - relative risks (95% confidence intervals [CI]) of 0.53 (0.39, 0.73) and 0.56 (0.41, 0.76) for SCOPE and LIFE, respectively. For fatal/non-fatal MI, there were greater discrepancies between the studies, but with neither achieving statistical significance compared with placebo - relative risks of 0.85 (0.59, 1.24) and 1.08 (0.80, 1.46) for SCOPE and LIFE, respectively. This analysis clearly demonstrates that both candesartan in SCOPE and losartan in LIFE are associated with reductions in stroke events compared with placebo, greater than that observed in the well-established meta-analysis of placebo-controlled hypertensive trials. However, the CIs are such that it is not possible to suggest definitively that this is a benefit beyond BP reduction alone. Neither trial is sufficiently 'powered' to demonstrate a benefit in CHD outcomes, but with SCOPE there was a trend towards benefit with a point estimate compatible with the major meta-analysis.
Aldosterone Synthase Inhibitors and Dietary Interventions: A Combined Novel Approach for Prevention and Treatment of Cardiovascular Disease. [2023]Systemic hypertension (HTN) is the hallmark of cardiovascular disease and the forerunner of heart failure. These associations have been established over decades of research on essential HTN. Advancements in the treatment of patients diagnosed with HTN, consisting of alpha- or beta-adrenergic receptor blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide, or aldosterone receptor blockers known as anti-mineralocorticoids, in the presence or absence of low sodium salt diets, often fail to control blood pressure adequately to prevent morbidity and mortality. Low sodium diets have had limited success in controlling HTN because low sodium intake is associated with renin-angiotensin-aldosterone system upregulation. Therefore, upregulating aldosterone secretion, sodium, and water retention which, in turn, moves the blood pressure back toward the range of HTN dictated by the baroreceptor reset value, as a compensatory mechanism, especially in resistant HTN. These impediments to blood pressure control in HTN may have been effectively circumvented by the advent of a new class of drugs known as aldosterone synthase inhibitors, represented by baxdrostat. The mechanism of action of baxdrostat as an aldosterone synthase inhibitor demonstrates the inextricable linkage between sodium and blood pressure regulation. Theoretically, combining a low sodium diet with the activity of this aldosterone synthesis inhibitor should alleviate the adverse effect of renin-angiotensin-aldosterone system upregulation. Aldosterone synthesis inhibition should also decrease the oxidative stress and endothelial dysfunction associated with HTN, causing more endothelial nitric oxide synthesis, release, and vasorelaxation. To the best of our knowledge, this is the first systematic review to summarize evidence-based articles relevant to the use of a novel drug (aldosterone synthase inhibitor) in the treatment of HTN and cardiovascular disease. Making the current database of relevant information on baxdrostat and other aldosterone synthase inhibitors readily available will, no doubt, aid physicians and other medical practitioners in their decision-making about employing aldosterone synthase inhibitors in the treatment of patients.
Baxdrostat: An Aldosterone Synthase Inhibitor for the Treatment of Systemic Hypertension. [2023]Systemic hypertension remains one of the leading cause of morbidity and mortality in the United States and throughout the world. Baxdrostat (CIN-107), a new drug developed by Roche is a selective aldosterone synthase inhibitor that is being evaluated as one of the potential treatments for hypertension, especially in patients with drug treatment-resistant hypertension. An increased level of aldosterone is associated with inflammation, systemic hypertension, and organ fibrosis, contributing to adverse cardiovascular events. A phase 2 trial, BrigHTN, showed promising results in demonstrating the efficacy of baxdrostat, where The HALO (efficacy and safety of baxdrostat in patients with uncontrolled hypertension) trial did not demonstrate any blood pressure-lowering benefit of baxdrostat when compared with the placebo. Several additional studies are now underway to evaluate the effectiveness of baxdrostat as an anti-hypertensive agent.
[The clinical efficacy of epristeride in the treatment of benign prostatic hyperplasia]. [2014]To estimate the clinical safety, efficacy of Epristeride in the treatment of benign prostatic hyperplasia (BPH).
Reporting of acute urinary retention in BPH treatment trials: importance of patient follow-up after discontinuation and case definitions. [2019]A growing number of reports of retrospective analyses of adverse events occurring during studies with alpha-blockers in men with benign prostatic hyperplasia (BPH) have compared acute urinary retention (AUR) event rates with placebo-controlled finasteride trials. Because of differences in study designs, the present analysis was undertaken to compare data on the rates of AUR across different BPH trials accurately.
Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group. [2022]The purpose of this open-label study extension was to assess the long-term safety and efficacy of finasteride in the treatment of men with benign prostatic hyperplasia (BPH).
Dietary supplements for benign prostatic hyperplasia: an overview of systematic reviews. [2015]Benign prostatic hyperplasia (BPH) is a common chronic condition in older men. The aim of this overview of systematic reviews (SRs) is to summarise the current evidence on the efficacy and adverse effects of dietary supplements for treating BPH with lower urinary tract symptoms. We searched 5 electronic databases and relevant overviews without limitations on language or publication status. Six SRs of 195 articles were included in this overview. Serenoa repens was reviewed in 3 studies and no specific effect on BPH symptoms and urinary flow measures was observed. However, β-sitosterol, Pygeum africannum and Cernilton were reviewed in one study each, and significant improvement was observed for all three. All the included compounds have mild and infrequent adverse effects. SRs on β-sitosterol, Pygeum africannum and Cernilton have not been updated since 2000, thus an update of reviews on these compounds will be necessary in the future.
Comparison of Saw Palmetto (extract and whole berry) and Cernitin on prostate growth in rats. [2019]Pharmaceuticals such as finasteride and alpha blockers are used to treat symptoms of benign prostatic hyperplasia (BPH) and are known to cause severe adverse reactions. Accordingly, a search for safer, natural products has been undertaken. Two natural agents (nutraceuticals) have come under recent scrutiny; because natural products, in general, often have evidence of long-term safety. The present study compares the in vivo effects on androgen-induced prostatic enlargement in rats of two nutraceuticals--the widely recognized Saw Palmetto (Serenoa repens) and the less well-known Cernitin (defined pollen extract). Non-castrated rats, had a mean prostate weight of 124 mg +/- 8.8 (S.E.M.) compared to the 24.5 mg +/- 1.9 (S.E.M.) of the castrated rat followed under the same regimen (p
Inhibition of testosterone 5 alpha-reductase by and antiandrogenicity of allenic 3-keto-5,10-secosteroids. [2019](4R)-5,10-seco-19-norpregna-4,5-diene-3,10,20-trione(II), A 3-keto-5,10-secosteroid which is an irreversible inhibitor of delta 5-3-ketosteroid isomerase was tested for its possible antiandrogenicity in the hamster flank organ test. The organs of female animals topically treated with 4 microgram of testosterone propionate (TP) for 4 weeks enlarged in size and showed pigmentation resembling adult males. When compound II was applied concomitantly with TP, androgenic stimulation was completely blocked and the flank organs remained small like those of female animals. These results suggest that compound II may be a useful anti-androgen when applied topically. It may well act mainly by inhibition of the formation of 5alphs-reduced metabolites was markedly inhibited.
Synthesis of new derivatives of 21-imidazolyl-16-dehydropregnenolone as inhibitors of 5α-reductase 2 and with cytotoxic activity in cancer cells. [2017]The aim of this study was to synthesize several 16-dehydropregnenolone derivatives containing an imidazole ring at C-21 and a different ester moiety at C-3 as inhibitors of 5α-reductase 1 and 2 isoenzymes. Their binding capacity to the androgen receptor (AR) was also studied. Additionally, we evaluated their pharmacological effect in a castrated hamster model and their cytotoxic activity on a panel of cancer cells (PC-3, MCF7, SK-LU-1). The results showed that only the derivatives with an alicyclic ester at C-3 showed 5α-R2 enzyme inhibition activity, the most potent of them being 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3β-yl-cyclohexanecarboxylate with an IC50 of 29nM. This is important because prostatic benign hyperplasia is directly associated with the presence of 5α-R2. However, all the derivatives failed to inhibit 5α-R1 or bind to the AR. These alicyclic ester derivatives decreased the weight and size of androgen-dependent glands in the hamster, indicating they are very active in vivo and are not toxic. In addition, the 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3β-yl-acetate derivative showed the highest cytotoxic activity on the three cancer cell lines studied. It is therefore important in the synthesis of steroidal compounds to consider the size of the ester moiety at C-3 of the steroid skeleton, which is key in obtaining biological activity, as observed in this experiment.
Aromatic esters of progesterone as 5alpha-reductase and prostate growth inhibitors. [2013]The aim of this study was to determine the biological activity of 4 steroidal derivatives (9a, 9b and 10a, 10b) prepared from the commercially available 17alpha acetoxyprogesterone, where 9a, 9b, have the Delta(4)-3-oxo structure and 10a and 10b an epoxy group at C-4 and C-5. These steroids were tested as inhibitors of 5alpha-reductase enzyme, which is present in androgen-dependent tissues and converts testosterone to its more active reduced metabolite dihydrotestosterone. The pharmacological effect of these steroids was demonstrated by the significant decrease of the weight of the prostate gland of gonadectomized hamsters treated with testosterone plus finasteride or with steroids 10a and 10b. For the studies in vitro the IC(50) values were determined by measuring the steroid concentration that inhibits 50% of the activity of-5alpha-reductase. In this study we also determined the capacity of these steroids to bind to the androgen receptor present in the rat prostate cytosol. The results from this work indicated that compounds 9a, 9b, 10a, and 10b inhibited the 5alpha reductase activity with IC(50) values of 360, 370, 13 and 4.9 nM respectively. However these steroids did not bind to the androgen receptors since none competed with labeled mibolerone. Steroid 10b, an epoxy steroidal derivative containing bromine atom in the ester moiety, was the most active inhibitor of 5alpha-reductase enzyme, present in human prostate homogenates with an IC(50) value of 4.9 nM and also showed in vivo pharmacological activity since it decreased the weight of the prostate from hamsters treated with testosterone in a similar way as finasteride.
Development of hormone-dependent prostate cancer models for the evaluation of inhibitors of 17beta-hydroxysteroid dehydrogenase type 3. [2009]17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) are responsible for the pre-receptor reduction/oxidation of steroids at the 17-position into active/inactive hormones, and the 15 known enzymes vary in their substrate specificity, localisation, and directional activity. 17beta-HSD Type 3 (17beta-HSD3) has been seen to be over-expressed in prostate cancer, and catalyses the reduction of androstenedione (Adione) to testosterone (T), which stimulates prostate tumour growth. Specific inhibitors of 17beta-HSD3 may have a role in the treatment of hormone-dependent prostate cancer and benign prostate hyperplasia, and also have potential as male anti-fertility agents. A 293-EBNA-based cell line with stable expression of transfected human 17beta-HSD3 was created and used to develop a whole cell radiometric TLC-based assay to assess the 17beta-HSD3 inhibitory potency of a series of compounds. STX2171 and STX2624 (IC(50) values in the 200-450nM range) were two of several active inhibitors identified. In similar TLC-based assays these compounds were found to be inactive against 17beta-HSD1 and 17beta-HSD2, indicating selectivity. A novel proof of concept model was developed to study the efficacy of the compounds in vitro using the androgen receptor positive hormone-dependent prostate cancer cell line, LNCaPwt, and its derivative, LNCaP[17beta-HSD3], transfected and selected for stable expression of 17beta-HSD3. The proliferation of the parental cell line was most efficiently stimulated by 5alpha-dihydrotestosterone (DHT), but the LNCaP[17beta-HSD3] cells were equally stimulated by Adione, indicating that 17beta-HSD3 efficiently converts Adione to T in this model. Adione-stimulated proliferation of LNCaP[17beta-HSD3] cells was inhibited in the presence of either STX2171 or STX2624. The compounds alone neither stimulated proliferation of the cells nor caused significant cell death, indicating that they are non-androgenic with low cytotoxicity. STX2171 inhibited Adione-stimulated growth of xenografts established from LNCaPwt cells in castrated mice in vivo. In conclusion, a primary screening assay and proof of concept model have been developed to study the efficacy of 17beta-HSD3 inhibitory compounds, which may have a role in the treatment of hormone-dependent cancer. Active compounds are selective for 17beta-HSD3 over 17beta-HSD1 and 17beta-HSD2, non-androgenic with low toxicity, and efficacious in both an in vitro proof of concept model and in an in vivo tumour model.
Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators. [2013]Herein we describe the discovery of ACP-105 (1), a novel and potent nonsteroidal selective androgen receptor modulator (SARM) with partial agonist activity relative to the natural androgen testosterone. Compound 1 was developed from a series of compounds found in a HTS screen using the receptor selection and amplification technology (R-SAT). In vivo, 1 improved anabolic parameters in a 2-week chronic study in castrated male rats. In addition to compound 1, a number of potent antiandrogens were discovered from the same series of compounds whereof one compound, 13, had antagonist activity at the AR T877A mutant involved in prostate cancer.