Study Design of a Phase 2 Trial of the Aldosterone Synthase Inhibitor BI 690517 Alone and in Combination With Empagliflozin in Patients With Diabetic and Non-Diabetic CKD
Kidney Week 2022
washington; spokane; pmrc
Elevated aldosterone levels are strongly associated with chronic kidney disease (CKD) progression. BI 690517 is an aldosterone synthase inhibitor that may reduce the deleterious mineralocorticoid receptor-dependent and -independent actions of aldosterone. Disruptions to aldosterone signalling increase the risk of hyperkalaemia, which may be mitigated by the addition of sodium–glucose cotransporter-2 inhibitors such as empagliflozin (EMPA). Thus, BI 690517 and EMPA may have a favourable safety profile and synergistic kidney protective activity.
This randomised, double-blind, placebo-controlled, parallel-dose Phase II trial (NCT05182840) will enrol ≥552 adults with CKD with or without type 2 diabetes; this will provide 90% power to detect a ≥15% change in urine albumin:creatinine ratio measured in first morning void urine (UACRFMV) with a one-sided 5% α at Week (W) 14. Eligible patients will have an estimated glomerular filtration rate (eGFR) ≥30 and <90 mL/min/1.73 m2, UACR ≥200 and <5000 mg/g, serum potassium ≤4.8 mmol/L and be receiving with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
Following an 8-week run-in period to assign background medication (EMPA 10 mg or matched placebo randomised 1:1), patients will be randomised 1:1:1:1 to receive BI 690517 (low, medium, or high dose) or matched placebo for 14 weeks (Figure).
The primary endpoint is change in UACRFMV from baseline to W14. Secondary endpoints are the proportion of patients with ≥15% and ≥30% decrease from baseline in UACRFMV at W14. Further endpoints include safety findings and change from baseline in eGFR and serum potassium at W14.
The trial is recruiting in 30 countries and 117 patients have been enrolled to date.
Kidney & Diabetes
Tuttle, Katherine and See full list of authors in comments, "Study Design of a Phase 2 Trial of the Aldosterone Synthase Inhibitor BI 690517 Alone and in Combination With Empagliflozin in Patients With Diabetic and Non-Diabetic CKD" (2022). Articles, Abstracts, and Reports. 6569.