14-week phase II data showed a significant reduction of albuminuria of up to 39.5% with a novel selective aldosterone synthase inhibitor on top of empagliflozin in patients with CKD, with or without diabetes.
A total of 714 participants were first randomized to receive either empagliflozin 10 mg or placebo for 8 weeks, they were then randomized for a second time (n=586) to receive one of three doses of the novel selective aldosterone synthase inhibitor (3 mg, 10 mg or 20 mg) or placebo for 14 weeks. All patients received background therapy with an ARB or ACEi. The primary endpoint was the percentage change in urine albumin creatinine ratio (UACR) from the second randomization to end of treatment. Key secondary endpoints were the proportion of patients with absolute decreases of ≥15% and ≥30% in UACR at week 14.
The largest placebo-corrected change in UACR was seen in participants who received the aldosterone synthase inhibitor at a dose of 10 mg on top of empagliflozin (-39.5% [CI -51.8 to -24.0]). A clinically meaningful reduction in UACR of ≥30% was achieved by up to 70% of patients treated with the novel selective aldosterone synthase inhibitor on top of empagliflozin.
There were no unexpected safety signals in the phase II trial. The rate of hyperkalemia was typical for a population with CKD. However, modest increases in serum potassium levels were observed in participants treated with the novel selective aldosterone synthase inhibitor. These increases were dose-dependent and were slightly improved in the presence of empagliflozin.
The phase III EASi-KIDNEY trial will test the efficacy and safety novel selective aldosterone synthase inhibitor in approximately 11,000 participants with established CKD. The trial will begin recruitment in 2024.