A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis

Table 3 Mean pharmacokinetic parameter estimate of brodalumab following multiple subcutaneous and intravenous doses given to rheumatoid arthritis patients ^a

	Predicted human exposure after multiple SC (n = 6) or IV (n = 2) doses		Exposure margin based on exposure in monkeys after 3-month weekly SC doses or 1-month weekly IV doses^b
Dose (mg)	AUC_0-t^c(μg/h/ml)	C_max(μg/ml)	AUC (μg/h/ml)	C_max(μg/ml)
50 (SC)	71.3	0.947	4,458	1,246
140 (SC)	2170	9.05	146	130
210 (SC)	6610	23.2	48	51
420 (IV)	24,800	113	126	89
700 (IV)	48,600	198	64	51

^aAUC, area under the curve; AUC_0-t, area under the serum concentration time curve; C_max, maximum serum concentration; IV, intravenous; SC, subcutaneous. ^bNo adverse effect level for monkeys is 90 mg/kg SC or 350 mg/kg IV. AUC_{0-168 hours} and C_max after the 12th dose of 90 mg/kg weekly SC were 159,000 μg/h/ml and 1,180 μg/ml, respectively. AUC_{0-168 hours} and C_max after fourth dose of 350 mg/kg weekly IV were 782 000 μg/h/ml and 10,100 μg/ml, respectively. ^cAUC_0-t = AUC_{0-336 hours} for SC cohorts and AUC_{0-672 hours} for IV cohorts.

ISSN: 1478-6362