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Baxdrostat is a selective aldosterone synthase inhibitor that has demonstrated dose-dependent seated office systolic BP (SBP) lowering in a Phase 2 trial of patients with rHTN. Here, we report the design of the baxdrostat hypertension Phase 3 program. BaxHTN (NCT06034743), BaxAsia (NCT06344104), and Bax24 (NCT06168409) are randomized, multi-national, double-blind, placebo-controlled Phase 3 trials evaluating the efficacy and safety of baxdrostat 1 and\/or 2\u2009mg versus placebo. BaxHTN includes patients with uHTN or rHTN, BaxAsia includes patients with uHTN or rHTN primarily from Asia, and Bax24 includes patients with rHTN. Eligibility criteria include age \u226518 years, mean seated office SBP of \u2265140\u2009mmHg to &lt;170\u2009mmHg at screening, and \u22652 antihypertensive treatments of different classes for \u22654 weeks before screening. BaxHTN and BaxAsia have four sequential periods following placebo run-in: 12-week double-blind; 12-week open-label; 8-week randomized withdrawal; 20-week open-label. Bax24 has a placebo run-in and 12-week double-blind period. Primary endpoints are changes from baseline to Week 12 in mean seated office SBP (BaxHTN and BaxAsia) and ambulatory 24-h average SBP (Bax24). Safety and tolerability are also assessed. The Baxdrostat hypertension Phase 3 program will assess efficacy, long-term sustained effect, and safety profile in patients with hypertension across multiple geographies. The trials will evaluate the BP lowering efficacy of aldosterone synthase inhibition as a novel treatment for uHTN and rHTN.<\/jats:p>","DOI":"10.1038\/s41440-025-02297-7","type":"journal-article","created":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T23:01:48Z","timestamp":1756076508000},"page":"2911-2923","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Baxdrostat for uncontrolled and resistant hypertension: rationale and design of the Phase 3 clinical trials BaxHTN, BaxAsia, and Bax24"],"prefix":"10.1038","volume":"48","author":[{"given":"John M.","family":"Flack","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Azizi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenifer M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie P.","family":"Dwyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika S. W.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aina S.","family":"Lihn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lylian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Olsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shira","family":"Perl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Guang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrica","family":"Wilder\u00e4ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet T.","family":"Wittes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"2297_CR1","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1016\/S0140-6736(18)32225-6","volume":"392","author":"GBD 2017 Risk Factor Collaborators.","year":"2018","unstructured":"GBD 2017 Risk Factor Collaborators. 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MA declares grants\/funding: AstraZeneca, Novartis, Recor Medical; consulting fees: AstraZeneca, Medtronic, Novartis, Recor Medical, Servier; honoraria: Novo Nordisk. JMB declares grants\/funding: American Heart Association, National Institutes of Health; consulting fees: AstraZeneca, Bayer Pharma AG. JPD declares employment: University of Utah; grants\/funding: AstraZeneca, CinCor Pharma; consulting fees: Alnylam Pharmaceuticals, AstraZeneca, Bayer Pharma AG, BD, Boehringer Ingelheim, CSL Behring, Eli Lilly and Company, GSK, Ionis Pharmaceuticals, Ipsen Biopharm, Recor Medical; board of directors: Corventum, Inc. ESWJ declares honoraria: AstraZeneca; academic support: AstraZeneca. ASL declares employment: AstraZeneca; stocks\/shares: AstraZeneca. LL declares employment: AstraZeneca; stocks\/shares: AstraZeneca. DSO declares employment: AstraZeneca; stocks\/shares: AstraZeneca. SP declares employment: AstraZeneca; stocks\/shares: AstraZeneca. HS declares honoraria: AstraZeneca, Bayer Pharma AG, Daiichi-Sankyo Company. J-GW declares grants\/funding: Huawei, Omron; consulting fees: AstraZeneca, Huawei, Novo Nordisk, SkyLabs, Viatris; honoraria: Idorsia, Viatris. UW declares employment: AstraZeneca; stocks\/shares: AstraZeneca. JTW declares consulting fees: AstraZeneca; advisory council\/committee: AstraZeneca. BW declares honoraria: Servier, Medtronic; consulting fees: Antlia Bioscience, AstraZeneca, Novartis; clinical trial investigator: AstraZeneca, Eli Lilly and Company, Novartis.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}