A randomized, phase I study of the safety, tolerability, and pharmacokinetics of BI 764198, a transient receptor potential channel 6 (TRPC6) inhibitor, in healthy Japanese men

BI 764,198 is a selective, oral transient receptor potential cation channel, subfamily C, member 6 inhibitor under investigation for focal segmental glomerulosclerosis. Phase I study in 44 Japanese male volunteers. Single dose part: BI 764,198 20 mg (<i>n</i> = 6) vs. placebo (<i>n</i> = 2); multiple dose part: BI 764,198 40, 80, or 160 mg (<i>n</i> = 9 each) or placebo (<i>n</i> = 9) as a single dose then multiple daily dosing for 2 weeks. Primary endpoint: participants with drug-related adverse events (DRAEs); secondary endpoints: pharmacokinetic. DRAEs were reported in 20.5% (9/44) of participants (total BI 764,198 21.2% [7/33]; placebo 18.2% [2/11]), mostly diarrhea (total BI 764,198 15.2% [5/33]; placebo 18.2% [2/11]) and headache (BI 764,198 80 mg 11.1% [1/9]; BI 764,198 160 mg 33.3% [3/9]). BI 764198 exposure increased near dose proportionally to 80 mg and was slightly higher than anticipated with 160 mg. Pharmacokinetics were similar in Asians and non-Asians after accounting for body weight. Limitations include small sample size per dose and short trial duration. BI 764,198 was well tolerated; exposure increased near dose proportionally to 80 mg, as previously observed in predominantly White volunteers. This study was registered on Clinical Trials.gov, identifier NCT04665700.