Abstract: SA-PO0242
Selectivity of Vicadrostat for Aldosterone Synthase Inhibition: Findings from a Phase 2 Trial in CKD
Session Information
- Pharmacology
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Gashaw, Isabella A, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
- Monroy Kuhn, Jose Manuel, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- Pleiner, Sina, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- Delic, Denis, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- Cronin, Lisa, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, United States
- Shah, Shimoli, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, United States
- Hauske, Sibylle Jenny, Boehringer Ingelheim International GmbH, Ingelheim, Germany
- Tuttle, Katherine R., Providence Inland Northwest Health, Spokane, Washington, United States
- Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Denmark
Background
Aldosterone synthase inhibitors may block cortisol synthesis due to homology between aldosterone and cortisol synthase enzymes. The selectivity of vicadrostat for aldosterone suppression was evaluated further by assessment of corticosteroid metabolites in a randomized, double-blind, placebo-controlled phase 2 trial (NCT05182840) of participants with CKD.
Methods
After an 8-week run-in on empagliflozin 10 mg or matched placebo on top of RAASi, 586 patients were randomized to 14 weeks of treatment with vicadrostat (3, 10 or 20 mg) or matching placebo, with a 4-week follow-up. The present analyses included 410 patients who completed treatment. Plasma corticosteroids were measured using LC-MS/MS. Mixed effects models for repeated measures were used to evaluate effects.
Results
Dose-dependent suppression of plasma aldosterone was observed, with maximum suppression at 14 weeks resulting in geometric mean changes of –49.5% (95% CI: –18.5, -68.7) and –52.1% (–21.6, –70.7) for 20 mg vicadrostat with and without empagliflozin, respectively (Table). The aldosterone precursor, 11-deoxycorticosterone, increased by 223% (103, 413) and 232% (106, 432) in plasma for 20 mg vicadrostat with or without empagliflozin, respectively. No change in plasma cortisol concentrations was observed across vicadrostat dose groups with or without empagliflozin. Post treatment, aldosterone suppression remained sustained up to 4 weeks, while precursor levels normalized within one week of treatment cessation.
Conclusion
Vicadrostat, with or without empagliflozin, selectively suppressed aldosterone levels, without any meaningful effects on cortisol. These findings will be explored further in EASi-HF Preserved™ (NCT06424288), EASi-HF Reduced™ (NCT06935370) and EASi-Kidney™ (NCT06531824) phase 3 trials.
Funding
- Commercial Support – Boehringer Ingelheim