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.

BACKGROUND: BI 764198 is a selective, oral transient receptor potential cation channel, subfamily C, member 6 inhibitor under investigation for focal segmental glomerulosclerosis. RESEARCH DESIGN AND METHODS: Phase I study in 44 Japanese male volunteers. Single dose part: BI 764198 20 mg (n = 6) vs. placebo (n = 2); multiple dose part: BI 764198 40, 80, or 160 mg (n = 9 each) or placebo (n = 9) as a single dose then multiple daily dosing for 2 weeks. Primary endpoint: participants with drug-related adverse events (DRAEs); secondary endpoints: pharmacokinetic. RESULTS: DRAEs were reported in 20.5% (9/44) of participants (total BI 764198 21.2% [7/33]; placebo 18.2% [2/11]), mostly diarrhea (total BI 764198 15.2% [5/33]; placebo 18.2% [2/11]) and headache (BI 764198 80 mg 11.1% [1/9]; BI 764198 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. CONCLUSIONS: BI 764198 was well tolerated; exposure increased near dose proportionally to 80 mg, as previously observed in predominantly White volunteers. CLINICAL TRIAL REGISTRATION: This study was registered on Clinical Trials.gov, identifier NCT04665700.