ALDOSTERONE SYNTHASE INHIBITION WITH OR WITHOUT BACKGROUND SODIUM GLUCOSE COTRANSPORTER 2 INHIBITION IN CKD: A PHASE II CLINICAL TRIAL

E-Poster

https://storage.unitedwebnetwork.com/files/1099/c5ee389920d675b1fcf1403a005bdac3.pdf

Abstract Title

First Name *

Katherine

Last Name *

Tuttle

Co-author 1

Sibylle Hauske sibylle.hauske@boehringer-ingelheim.com Boehringer Ingelheim International GmbH CMR Medicine Ingelheim am Rhein Vth Department of Medicine, University Medical Center Mannheim, Heidelberg University

Co-author 2

Shimoli V Shah shimoli.shah@boehringer-ingelheim.com Boehringer Ingelheim Pharmaceuticals Inc. Global Patient Safety & Pharmacovigilance Ridgefield

Co-author 3

Lisa Cronin lisa.cronin@boehringer-ingelheim.com Boehringer Ingelheim Pharmaceuticals Inc. CardioMetabolism & Respiratory Medicine Ridgefield

Co-author 4

Zhichao Sun zhichao.sun@boehringer-ingelheim.com Boehringer Ingelheim Pharmaceuticals Inc. Global Biostatistics & Data Sciences Ridgefield

Co-author 5

Dick de Zeeuw ZeeuwDrugAdvice@outlook.com University Medical Center Groningen Department of Clinical Pharmacy and Pharmacology Groningen

Co-author 6

Hiddo J L Heerspink h.j.lambers.heerspink@umcg.nl University Medical Center Groningen Department of Clinical Pharmacy and Pharmacology Groningen

Co-author 7

Peter Rossing peter.rossing@regionh.dk Steno Diabetes Center Copenhagen Complications Research Copenhagen

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

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 patients with CKD.

Methods

In this double-blind, dose-finding 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 empagliflozin 10 mg or placebo (PBOEMPA) and then randomized a second time (R2) 1:1:1:1 to BI 690517 (3, 10 or 20 mg) or PBOASI for 14 weeks. The primary endpoint was change from R2 baseline in urine albumin:creatinine ratio in first morning void urine (UACRFMV) at Week 14. A secondary endpoint was UACRFMV response (≥30% change from R2 baseline in UACRFMV at Week 14). Safety was also assessed.

Results

Of 714 patients randomized in R1, 586 were randomized in R2. At R2 baseline, mean (SD) age was 63.8 (11.3) years, 58.4% of patients were White, 66.6% male, and 70.6% had type 2 diabetes. Baseline 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 empagliflozin background. Among BI 690517 3–20mg patients, changes in UACR ≥30% were achieved by 53.5% of patients on empagliflozin background and 43.2% of those on PBOEMPA background. BI 690517 (3–20mg)-related adverse events were reported in 19.2% of patients on empagliflozin background and 18.5% of those on PBOEMPA background.

Conclusions

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

This abstract was also submitted for the ASN Kidney Week 2023 congress; Tuttle K, et al: Aldosterone Synthase Inhibition with or without Background Sodium Glucose Cotransporter 2 Inhibition in CKD: A Phase II Clinical Trial [#FR-OR111]. By submitting the abstract to WCN’24, abstract authors declare that re-submitting the abstract is permitted by the organizers of the previous meeting.

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