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Fig. 1 | Arthritis Research & Therapy

Fig. 1

From: Safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06650833, a selective interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, in single and multiple ascending dose randomized phase 1 studies in healthy subjects

Fig. 1

Design and PF-06650833 final dosing scheme in a study 1 (SAD) and b study 2 (MAD). aPK and PD sampling time was up to 96 h for cohorts 1 and 2. Subjects in cohorts 3 and 4 were followed up to day 21 of the final period to better characterize the terminal phase, given the potentially long elimination half-life based on emerging data. bDose administered after consumption of a high-fat breakfast meal. cAlternate IR formulation. dCohort 3 consisted of only four periods, and cohort 4 consisted of only two periods that were separated by 14 days, in order to maintain the overall predicted exposure in an individual subject to ≤ 28 days. In study 1, within each period, 8 subjects were randomized to receive PF-06650833 and 2 subjects were randomized to receive placebo. All subjects within a cohort received one or more doses of PF-06650833 and/or placebo. Doses were escalated sequentially within each period, based on evaluation of ≥ 48 h of safety and tolerability for all subjects and ≥ 8 h of PK data for at least 6 subjects receiving PF-06650833 and 1 subject receiving placebo. All doses were administered orally under fasting conditions (overnight fast of ≥ 10 h) unless otherwise indicated. In study 2, within each cohort, eight subjects were planned to receive PF-06650833 and 2 subjects were planned to receive placebo. All doses were administered orally under standard (not high-fat) meal, fed conditions. QD doses were 24 h apart, BID doses were 12 h apart, TID doses were 8 h apart, and QID doses were 6 h apart. When dosing in the fed condition, the morning and evening doses were administered within 5 min of completing the standard meal. BID twice daily; IR immediate-release: MAD multiple ascending doses; MR modified-release; PK pharmacokinetics; QD once daily; QID four times per day; SAD single ascending doses; TID three times per day

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