| In Vivo |
GS-9901 (0.3/1/3 mg/kg, orally, twice daily for 7 days) demonstrates efficacy in a rat model of arthritis and is predicted to be suitable for q.d. dosing in humans[1]. Animal Model: Female Lewis rats with established collagen-induced arthritis (CIA)[1]. Dosage: 0.3 mg/kg, 1 mg/kg, and 3 mg/kg. Administration: Orally, twice-daily for 7 days starting on the 10th day after the second collagen immunization. Result: Demonstrated significant reduction in ankle swelling in rats treated with 0.3 mg/kg 35 (31% reduction), 1 mg/kg 35 (67%), and 3 mg/kg 35 (65%). Plasma concentrations measured on day 7 (12 h after last dose) were consistent with maintaining approximately 60%, 80%, and >90% inhibition of PI3Kδ at 0.3, 1.0, and 3 mg/kg doses, respectively, at trough levels.
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