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Abstract: FR-OR111

Aldosterone Synthase Inhibition with or Without Background Sodium Glucose Cotransporter 2 Inhibition in CKD: A Phase II Clinical Trial

Session Information

Category: CKD (Non-Dialysis)

  • 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Tuttle, Katherine R., University of Washington, Seattle, Washington, United States
  • Hauske, Sibylle Jenny, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
  • Cronin, Lisa, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
  • Sun, Zhichao, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
  • de Zeeuw, Dick, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Heerspink, Hiddo Jan L., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark

Group or Team Name

  • On behalf of the Steering Committee
Background

High aldosterone levels accelerate chronic kidney disease (CKD) progression. We tested the efficacy and safety of BI 690517, a novel aldosterone synthase inhibitor (ASI), in participants (pts) with CKD.

Methods

In this double-blind trial (NCT05182840), adults with CKD on a renin angiotensin system inhibitor (RASi) were first randomized (R1) 1:1 to an 8-week run-in to background (BG) empagliflozin 10 mg (EMPA) or placebo (PBOEMPA) and then randomized a second time (R2) 1:1:1:1 to BI 690517 (3, 10, or 20 mg) or PBOASI. The primary endpoint was change from R2 baseline (BL) in urine albumin:creatinine ratio (UACR) from the first morning void at Week 14. A secondary endpoint was UACR ≥30% reduction from R2 BL at Week 14.

Results

Of 714 pts randomized in R1, 586 were randomized in R2. At R2 BL, mean (SD) age was 63.8 (11.3) years, 58.4% of pts were White, 66.6% were male, and 70.6% had type 2 diabetes. BL median (IQR) UACR was 426.3 (205–889) mg/g and mean (SD) eGFR was 51.9 (17.7) mL/min/1.73m2. BI 690517 dose dependently reduced UACR (Figure). Largest median (95% CI) PBOASI-corrected change was −39.5% (−51.8, −24.0) for BI 690517 10 mg on EMPA BG. Among BI 690517 3–20mg pts, changes in UACR ≥30% were achieved by 53.5% on EMPA BG and 43.2% on PBOEMPA BG. BI 690517 (3–20mg)-related adverse events were reported in 19.2% of pts on EMPA BG and 18.5% of those on PBOEMPA BG.

Conclusion

BI 690517 was well tolerated and dose dependently reduced UACR on top of BG RASi and EMPA/PBOEMPA in pts with CKD. BI 690517 and EMPA showed additive anti-albuminuric efficacy that may translate into greater kidney protection.

Percentage change from R2 BL in UACR up to Week 14 following BI 690517 treatment administered with A) EMPA-matched placebo or B) EMPA 10 mg.

Funding

  • Commercial Support – Boehringer Ingelheim