Expert opinion on investigational drugs · 2026
Mass balance and absolute bioavailability of avenciguat (14C) after intravenous or oral administration in healthy male participants.
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Joseph David, Wong Diane, Mitra Pallabi, Auclair Adam M, Wolfgang Taylor, Gao Eric, Herich Lena, Tiessen Renger
Аннотация
BACKGROUND: Avenciguat, a potent nitric oxide-independent activator of soluble guanylyl cyclase, is being evaluated in chronic kidney disease and systemic sclerosis. We assessed avenciguat absolute bioavailability and mass balance.
RESEARCH DESIGN AND METHODS: Open-label Phase 1 trial in healthy men. Doses: Part A, 3 mg [14C]-avenciguat single dose (oral solution); Part B, 3 mg unlabeled avenciguat (tablet) then 30 µg [14C]-avenciguat (intravenous). Primary endpoints: Part A, mass balance and recovery of [14C] radioactivity in excreta; Part B, absolute bioavailability. Safety and pharmacokinetics were evaluated.
RESULTS: In Part A (N = 6), geometric mean recovery of [14C] radioactivity was 90.0% (range 80.6-96.0%). Elimination was mainly via feces (geometric mean 85.3%; range 76.5-91.3%); urine (4.66%; range 4.10-5.31%). In Part B (N = 6), the absolute bioavailability of avenciguat was 83.0%. In pooled plasma, the predominant drug-related component was avenciguat (mean 86.8%); the acyl glucuronide metabolite represented 5.2% of radioactivity. Drug-related adverse events (AEs) occurred in 33.3% (4/12) of participants, mostly mild, with one moderate presyncope event. No AEs leading to discontinuation were reported.
CONCLUSIONS: Avenciguat was generally well tolerated and was primarily excreted unchanged in feces and minimally excreted in urine. After oral administration, avenciguat has high oral bioavailability.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT05515328).
RESEARCH DESIGN AND METHODS: Open-label Phase 1 trial in healthy men. Doses: Part A, 3 mg [14C]-avenciguat single dose (oral solution); Part B, 3 mg unlabeled avenciguat (tablet) then 30 µg [14C]-avenciguat (intravenous). Primary endpoints: Part A, mass balance and recovery of [14C] radioactivity in excreta; Part B, absolute bioavailability. Safety and pharmacokinetics were evaluated.
RESULTS: In Part A (N = 6), geometric mean recovery of [14C] radioactivity was 90.0% (range 80.6-96.0%). Elimination was mainly via feces (geometric mean 85.3%; range 76.5-91.3%); urine (4.66%; range 4.10-5.31%). In Part B (N = 6), the absolute bioavailability of avenciguat was 83.0%. In pooled plasma, the predominant drug-related component was avenciguat (mean 86.8%); the acyl glucuronide metabolite represented 5.2% of radioactivity. Drug-related adverse events (AEs) occurred in 33.3% (4/12) of participants, mostly mild, with one moderate presyncope event. No AEs leading to discontinuation were reported.
CONCLUSIONS: Avenciguat was generally well tolerated and was primarily excreted unchanged in feces and minimally excreted in urine. After oral administration, avenciguat has high oral bioavailability.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT05515328).