Single and multiple doses of BI 690517 up to 80 mg were well tolerated, with drug-related adverse events occurring in 2.8% to 21.4% of participants and no serious adverse events reported.
RCT (n=212)
Mixed (Double-blind, Single-blind, Open-label)
Randomized within dose groups (for 3 of 4 studies)
Yes
Is BI 690517 (vicadrostat) safe and well-tolerated in healthy male volunteers?
BI 690517 (vicadrostat), a novel aldosterone synthase inhibitor, is well tolerated and effectively inhibits aldosterone synthesis in healthy male volunteers.
PURPOSE: In chronic kidney disease (CKD), raised plasma aldosterone levels are strongly associated with adverse cardiorenal outcomes. Current standard of care may improve outcomes; however, elevated aldosterone levels often persist. We report safety results for BI 690517 (vicadrostat), a potent, selective aldosterone synthase inhibitor under investigation for CKD. METHODS: Four phase 1 studies of BI 690517 conducted in healthy European/Chinese/Japanese men: two single rising dose (SRD) and two multiple rising dose (MRD) studies. PRIMARY ENDPOINT: proportion of participants with investigator-defined drug-related adverse events (AEs). RESULTS: Single and multiple doses of BI 690517 ≤ 80 mg (0.7-80 mg European SRD; 3-80 mg Chinese/Japanese SRD and MRD) were well tolerated. Proportions of participants with drug-related AEs: European SRD, 8.3% (4/48); Chinese/Japanese SRD, 21.4% (12/56); European MRD, 13.9% (10/72); Japanese MRD, 2.8% (1/36). No serious AEs, deaths, or AEs leading to treatment discontinuation were reported; one AE of severe orthostatic hypotension occurred (European SRD). Plasma exposure to BI 690517 increased dose dependently; median time to maximum concentration was 0.50-1.75 h and mean half-life was 4.4-6.3 h. Exposure was slightly higher in Asians versus Europeans and may relate to lower body weight in Asian participants. A standardized high-fat/high-calorie meal reduced the rate, but not extent, of BI 690517 absorption. Plasma aldosterone concentrations decreased markedly 1-2 h after BI 690517 administration; decreases were more pronounced with increasing BI 690517 doses. CONCLUSION: BI 690517 was well tolerated and demonstrated dose-dependent inhibition of aldosterone synthesis. Larger studies are warranted to confirm these findings.
Schulze et al. (Mon,) conducted a rct in Healthy volunteers (n=212). BI 690517 (vicadrostat) vs. Placebo was evaluated on Proportion of participants with investigator-defined drug-related adverse events (AEs). Single and multiple doses of BI 690517 up to 80 mg were well tolerated, with drug-related adverse events occurring in 2.8% to 21.4% of participants and no serious adverse events reported.