Baxdrostat for uncontrolled and resistant hypertension: rationale and design of the Phase 3 clinical trials BaxHTN, BaxAsia, and Bax24

Hypertens Res. 2025 Nov;48(11):2911-2923. doi: 10.1038/s41440-025-02297-7. Epub 2025 Aug 25.

Abstract

Inappropriately elevated aldosterone is a common feature of uncontrolled hypertension (uHTN) and resistant hypertension (rHTN), and is a major pathophysiological driver of adverse cardiorenal outcomes beyond elevated blood pressure (BP). 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 mg 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 ≥18 years, mean seated office SBP of ≥140 mmHg to <170 mmHg at screening, and ≥2 antihypertensive treatments of different classes for ≥4 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.

Keywords: Aldosterone; Aldosterone synthase inhibitor; Antihypertensive agents; Baxdrostat; Hypertension.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Antihypertensive Agents* / therapeutic use
  • Blood Pressure / drug effects
  • Clinical Trials, Phase III as Topic
  • Cytochrome P-450 CYP11B2 / antagonists & inhibitors
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension* / drug therapy
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic

Substances

  • Antihypertensive Agents
  • Cytochrome P-450 CYP11B2