A randomised, double blind, placebo controlled single ascending dose study of PYM50018, with an open label cross-over stage to assess food effect

Abstract

Background and Aims PYM50018 has neuroprotective properties and an emerging safety profile that make it a promising candidate for the treatment of neurodegenerative disorders, such as amyotrophic lateral sclerosis. This study evaluated the pharmacokinetics, safety and tolerability of the compound, together with the effect of food on its bioavailability. Methods Forty healthy males 18 to 45 years who met the entry criteria were included. Four groups of ten subjects were randomly allocated to receive placebo (n=2) or PYM50018 (n=8; 80 mg, 240 mg, 480 mg or 960 mg). One group also received PYM50018 (240 mg) on two further occasions either after breakfast or fasted. Results Exposure to PYM50018 increased proportionately with dose. At higher exposures a second, slower elimination phase became apparent. Exposure to PYM50018 was increased after a high fat breakfast, as compared with the fasted state. There were no clinically significant changes in the safety parameters or adverse events. Conclusions PYM50018 is well tolerated by healthy male subjects as a single oral dose of up to 960 mg. Systemic exposure to oral PYM50018 is dose proportional. Food has a significant effect on the absorption kinetics of PYM50018. Clinical Pharmacology & Therapeutics (2005) 77, P67–P67; doi: 10.1016/j.clpt.2004.12.146