Systolic plood pressure response to ASi BI 690517 with and without empagliflozin in CKD

Abstract

Abstract Background and Aims: BI 690517 is a highly selective aldosterone synthase inhibitor (ASi) in clinical development for CKD treatment. Coadministration of BI 690517 with a sodium-glucose cotransporter-2 inhibitor may provide additive efficacy and also mitigate risk of hyperkalaemia. This multinational, randomised, dose-finding, Phase II trial (NCT05182840) investigated the efficacy and safety of BI 690517, given alone or in combination with empagliflozin (EMPA), for albuminuria reduction in people with CKD and with or without type 2 diabetes.1 Here, we present a secondary analysis for effects on systolic blood pressure (SBP). Method Adults with CKD receiving a maximally tolerated dose of a renin-angiotensin system inhibitor were randomised (R1) 1:1 to receive background EMPA 10 mg or placebo (PBO-EMPA) during an 8-week run-in. They were then re-randomised (R2) 1:1:1:1 to receive BI 690517 (3 mg, 10 mg, or 20 mg) or PBO-ASI for 14 weeks, in addition to their assigned EMPA or PBO-EMPA therapy. Participants had mean baseline SBP ≥110 and ≤160 mmHg. Elevated blood pressure (BP) was defined as SBP ≥140 mmHg or DBP ≥90 mmHg and receiving ≥2 classes of anti-HTN medication. Changes in SBP from R2 baseline to Week 14 were analysed to assess BI 690517 effects with and without EMPA use. Results Of 714 people randomised at R1, 586 were randomised at R2, and the treated set consisted of 583 people. Demographics and clinical characteristics were similar between dose groups.1 At R2 baseline, 169 (29.0%) people had elevated BP. Mean SBP was 142.7 mmHg in the elevated BP group versus 129.2 mmHg in the non-elevated BP group. Treatment with BI 690517 consistently reduced SBP with reductions that were comparable in people with and without elevated BP (p-value for interaction not significant) (Table). Conclusions In people with CKD, BI 690517 reduced SBP in people with and without elevated BP.(Table)