Phase 1 trials of BI 764198, a transient receptor potential channel 6 inhibitor, in healthy volunteers and participants with kidney impairment.

BACKGROUND: BI 764198 could reduce podocyte injury in focal segmental glomerulosclerosis (FSGS). RESEARCH DESIGN AND METHODS: Four Phase 1 BI 764198 trials: single rising dose (SRD) and multiple rising dose (MRD)/drug-drug interaction trials in healthy volunteers; relative bioavailability (rBA) study (food and formulations effects on pharmacokinetics; PK); and kidney impairment (KI) PK study. RESULTS: SRD trial: 4/54 BI 764198-treated participants (7.4%) had ≥ 1 investigator-defined drug-related adverse event (DRAE): headache (n = 3; 5.6%); diarrhea (n = 1; 16.7%). BI 764198 PK was approximately linear. MRD trial: DRAEs occurred in 5/32 (15.6%) participants receiving BI 764198 and 1/8 (12.5%) receiving placebo. Once-daily BI 764198 80 mg (10 days) did not alter midazolam PK. All BI 764198 formulations tested had similar rBA; food did not affect PK. KI study: geometric mean ratios for area under the plasma concentration-time curve were 147.8% and 177.7% for participants with moderate and severe KI, respectively (vs. without). Limitations include typically small Phase 1 sample sizes and open-label design for the rBA and KI trials. CONCLUSIONS: BI 764198 was well tolerated and could be taken with/without food; evaluation in FSGS is ongoing. CLINICAL TRIAL REGISTRATION: The trials are registered at www.clinicaltrials.gov with codes NCT03854552; NCT04102462; NCT04656288; NCT04176536.