P358 Risk of incident cancer in patients with inflammatory bowel disease starting anti-TNF therapy while having prior malignancy within past 5 years (GETAID survey)

Abstract

electrocardiogram, telemetry, and physical exam. The PK of RPC1063 and its metabolites in plasma was evaluated using a validated LC-MS/MS assay and a non-compartmental method. Results: The upper 95% 1-sided confidence limit for QTc change from BL was always below 10 msec at both 1mg and 2mg doses, meeting pre-specified criteria to rule out a relevant QT effect of RPC1063. Assay sensitivity was demonstrated with QTc change from BL>5ms following MXF treatment. DT was well tolerated, attenuated first dose effects, and minimized decreases in HR throughout titration period. Generally, RPC1063 treatment was well tolerated. AEs, including cardiac AEs, were similar in RPC1063 and control groups, and similar to those seen previously with RPC1063. Most common AEs were administration site reaction, headache, orthostatic hypotension, dizziness, musculoskeletal chest pain and constipation. No SAEs occurred in the study. Two active metabolites that retain the S1P1R potency and selectivity of the parent were measurable at concentrations sufficient to derive PK parameters. The PK of the metabolites was similar to that of RPC1063, characterized by a late Tmax (6 8hrs), an elimination half-life of 19 22 hours, and low intersubject variability. Conclusions: The study confirmed the absence of a relevant effect of RPC1063 on QTc prolongation. Overall, the emerging favourable cardiac, safety, and PK profiles of RPC1063 support its development in UC and MS.