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A phase 1, placebo-controlled, randomised, double-blind (within dose panels) study evaluating the safety, tolerability and pharmacokinetics of intravenous NXY-059 in Japanese subjects

ABSTRACT Objective: NXY‑059 has a proposed mechanism of action of free-radical trapping and has been studied in clinical trials based on positive effects seen in experimental models of acute ischaemic stroke. This study evaluated the safety, tolerability and pharmacokinetics of NXY‑059 in healthy Japanese male subjects compared with previous data from healthy Caucasian subjects. Research design and methods: The primary objective of this phase 1, double-blind, randomised, placebo-controlled, dose-escalating study was to evaluate the safety and tolerability of an 8- or 24‑h intravenous infusion of NXY-059 targeting an unbound plasma concentration of 25–300 μmol/L in healthy Japanese male subjects (20–45 years). NXY‑059 pharmacokinetics were also assessed, and any differences in pharmacokinetics between Japanese and previously studied Caucasian subjects (20–45 years) were explored. Results: NXY‑059 was generally well tolerated and no safety concerns were identified. There was a similar incidence of adverse events between subjects receiving NXY‑059 or placebo, and no obvious trend towards an increased incidence of adverse events with increasing doses of NXY‑059 was observed. In addition, there was no evidence of any vasoirritative effects or changes in renal function. The tolerability profile was similar in Caucasian subjects. The pharmacokinetic results indicate proportional exposure of 8‑h and 24‑h infusions of NXY‑059 resulting in mean unbound steady state plasma concentrations up to 417 μmol/L and 379 μmol/L, respectively. Plasma clearance values for NXY‑059 were similar in both Japanese and Caucasian subjects. Conclusions: This study suggests that the tolerability and pharmacokinetics of NXY‑059 in healthy Japanese male subjects and Caucasians are similar.