Abstracts of 11th C1-inhibitor Deficiency & Angioedema Workshop

Table 1 PK and PD parameters in healthy subjects and HAE subjects after single oral single doses of BCX7353

Population	N	Dose of BCX7353 mg	C ^a_max ng/mL	AUC ^a_0-24 ng h/mL	[7353] > 8×EC₅₀ at 0.5,1,8,24 h n	KKI at 30 min^b %	KKI at 24 h^b %
Healthy subjects	6	250	104 (24)	995 (25)	0,3,1,0	12 (44)	24 (18)
Healthy subjects	6	500	245 (59)	2700 (43)	0,4,6,0	50 (26)	72 (10)
HAE subjects^c	6	750	584 (26)	5670 (17)	6,6,6,6	80 (7)	81 (11)

^aPK parameters are geometric mean (% coefficient of variation)
^bPD parameters are mean (standard deviation) in an in ex vivo assay (note that n = 5 in HAE subjects), and results reported are percent reduction in specific amidolytic activity from pre-dose sample. As the reagent volume dilutes the plasma sample 4-fold, BCX7353 concentration ex vivo is 25% of that present in vivo postdosing. The reported ex vivo % inhibition therefore underestimates the in vivo inhibitory activity achieved. For example, a value of 80% inhibition ex vivo corresponds to approximately > 94% inhibition in vivo
^cPK study in subjects with HAE was conducted at an HAE reference center at University Hospital, Frankfurt, Germany

ISSN: 1710-1492