BACKGROUND: NXY-059 is a free radical-trapping neuroprotectant that has been 
reported to reduce infarct size and preserve brain function in experimental 
models of acute ischemic stroke. NXY-059 administered as an 8- or 72-hour IV 
infusion has been reported to be well tolerated in healthy young (age, 20-45 
years) and older (55-75 years) white volunteers. NXY-059 is no longer in 
development following a lack of efficacy found in a Phase III trial in patients 
with acute ischemic stroke.
OBJECTIVES: The primary objectives of this study were to determine the 
pharmacokinetic (PK) properties of an 8-hour IV infusion of NXY-059 in healthy 
Chinese volunteers and to compare those data with those previously reported in 
the white population, therefore exploring any differences in PK properties 
between the 2 ethnic groups. Secondary objectives were to evaluate PK linearity 
and tolerability.
METHODS: This Phase I, randomized, double-blind (within dose panels), 
placebo-controlled study was conducted at Peking Union Medical College Hospital, 
Beijing, China. Healthy male and female Chinese volunteers aged 20 to 45 years 
were recruited. NXY-059 was administered as a continuous 8-hour IV infusion, 
starting with a 1-hour loading dose (dosing rate, 3 x maintenance infusion rate) 
followed by a 7-hour maintenance dose infusion. Subjects were randomly assigned, 
in a 3:1 ratio, to receive doses calculated (based on creatinine clearance in 
individual subjects) to achieve 1 of 3 concentration targets, or inactive 
vehicle (sodium chloride; placebo). The target unbound plasma NXY-059 
concentrations during constant rate infusion (steady state) (Cu(ss)) in the 3 
dose panels were 100,200, and 300 micromol/L. An explorative bridging analysis 
was used to compare PK data from this study with those previously reported in 
the white population. Linearity of NXY-059 PK properties was assessed. 
Tolerability was assessed using adverse events (spontaneous reporting, study 
staff observation, and open questioning), physical examination, including vital 
sign measurement; and electrocardiography and laboratory analysis.
RESULTS: Thirty-six subjects were randomized (mean age, 32 years [range, 20-41 
years]; mean body mass index, 22.6 kg/m(2) [range, 20-26 kg/m(2)]). The target 
exposures of NXY-059 were achieved (mean [SD] Cu(ss) values, 98.3 [8.9], 202.1 
[18.3], and 287.9 [25.4] micromol/L, respectively). Steady-state concentrations 
appeared to have been reached after 4 hours. From the bridging analysis, 
comparison of PK properties in the 27 Chinese volunteers versus those in 28 
white volunteers found similar total plasma clearance of NXY-059 (estimated 
Chinese:white clearance ratio, 1.077 [95% CI, 1.009-1.150]). There were no 
apparent differences in other PK parameters between the 2 ethnic groups. The PK 
properties of NXY-059 in Chinese volunteers were suggestive of linearity. A 
total of 7 adverse events were reported, all of mild intensity, in the NXY-059 
and placebo groups (thirst and polyuria [each in 2 subjects who received NXY-059 
and 1 subject who received placebo]; urinary tract infection [1 subject who 
received NXY-059]).
CONCLUSIONS: The results from the present study suggest that the PK properties 
of NXY-059 were similar in the Chinese and historical white healthy volunteer 
populations.