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NXY-059, the first nitrone being developed for stroke, is safe and well tolerated in elderly healthy volunteers
ABSTRACTS
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NXY-059, the first nitrone being developed for stroke, is safe and well tolerated in elderly healthy volunteers S Strid, C Edenius, K Lanbeck-Vall6n, L Dalin and B Fransson, S6dert~ilje, SWEDEN
Background: NXY-059 is a nitrone with free radical trapping properties, shown to be effective in preclinicat stroke models. It has been demonstrated to be safe and well tolerated in young healthy volunteers when given as an 8 hour intravenous infusion. Methods: NXY-059 or placebo was infused for 24 or 72 hours, including a 1 hour loading dose, to 24 (6 placebo) elderly healthy male and female volunteers (57-72 years). Doses were individualized according to renal function and the maintenance dose ranged between 40-129 mg/h. Results: The steady state plasma concentration achieved in the 72 hours dose group was 60 laM (unbound 38 pM). NXY-059 was well tolerated with few adverse events (AE) reported. Headache, dizziness, fatigue and post vessel puncture heamatoma were the most frequent AEs, each occurring in 3 out of 18 NXY-059 treated subjects. No clinically relevant changes were observed on vital signs, ECG or laboratory parameters. The main pharmacokinetic variables were: plasma CL: 69 mL/min, distribution volume at steady state: 13 L, elimination half-life: 3.9 hours and fraction excreted unchanged: 0.89. Plasma CL was positively correlated to creatinine CL. Conclusion: Intravenous administration of NXY-059 for 72 hours is safe and well tolerated in healthy elderly volunteers at anticipated therapeutic plasma concentrations.
Elementary neurological deficits versus disorders of higher cortical function impairment as presentations of stroke: A mini meta analysis of three large stroke registries. Hoffmann M (1) Pettigrew LC (1,2). Department or Neurology (1) and Stroke Program (2), Sanders-Brown Center on Aging, University of Kentucky Medical Center, Lexington Kentucky. Background: Elementary neurological signs that are traditionally and classically associated with stroke are unilateral weakness, numbness and vision impairment singly or in various combinations. The National Stroke Association lists six major symptoms of acute stroke with disorders of higher cortical function (HCF) poorly represented in these major categories Aim: The frequency of impaired cortical function with and without elementary neurological syndromes of motor and sensory impairment in three hospital based stroke registries, Patient population: Retrospective mini metanalysis of three large stroke registries N INDS (n=1805). DSDB (n=1281), Kentucky Stroke Registry (KYSR) (n=4715). Methods: The three most common behavioural syndromes representing large scale cognitive networks (aphasias and neglect syndromes) and regional (apraxias) were analysed as to their frequencies with and without accompanying sensorimotor deficits. Patients who had suppressed consciousness were excluded. Behavioural syndromes were predefined in all data banks Results: Range of HCF frequencies were21-37%, The individual registries were NiNDS: 310/120 (25.7%), DSDB 434/1170 (37 1%) and KYSR 1037/4715 (21.9%). Comparison of HCF with and without sensorimotor deficits revealed were significant in all three registries, Conclusion: Diverse cultural and linguistic backgrounds may not be associated with unique patterns of brain development. HCF are frequent in stroke and in a significant proportion of stroke patients cognitive impairment is the sole presenting neurological deficit. This necessitates a systematic higher cortical function appraisal. This is the first report of combined stroke registry data taken from multinational, multilingual and multiracial sources.
286
NXY-059, the first nitrone being developed for stroke, is safe and well tolerated in elderly healthy volunteers S Strid, C Edenius, K Lanbeck-Vall6n, L Dalin and B Fransson, S6dert~ilje, SWEDEN
Background: NXY-059 is a nitrone with free radical trapping properties, shown to be effective in preclinicat stroke models. It has been demonstrated to be safe and well tolerated in young healthy volunteers when given as an 8 hour intravenous infusion. Methods: NXY-059 or placebo was infused for 24 or 72 hours, including a 1 hour loading dose, to 24 (6 placebo) elderly healthy male and female volunteers (57-72 years). Doses were individualized according to renal function and the maintenance dose ranged between 40-129 mg/h. Results: The steady state plasma concentration achieved in the 72 hours dose group was 60 laM (unbound 38 pM). NXY-059 was well tolerated with few adverse events (AE) reported. Headache, dizziness, fatigue and post vessel puncture heamatoma were the most frequent AEs, each occurring in 3 out of 18 NXY-059 treated subjects. No clinically relevant changes were observed on vital signs, ECG or laboratory parameters. The main pharmacokinetic variables were: plasma CL: 69 mL/min, distribution volume at steady state: 13 L, elimination half-life: 3.9 hours and fraction excreted unchanged: 0.89. Plasma CL was positively correlated to creatinine CL. Conclusion: Intravenous administration of NXY-059 for 72 hours is safe and well tolerated in healthy elderly volunteers at anticipated therapeutic plasma concentrations.
Elementary neurological deficits versus disorders of higher cortical function impairment as presentations of stroke: A mini meta analysis of three large stroke registries. Hoffmann M (1) Pettigrew LC (1,2). Department or Neurology (1) and Stroke Program (2), Sanders-Brown Center on Aging, University of Kentucky Medical Center, Lexington Kentucky. Background: Elementary neurological signs that are traditionally and classically associated with stroke are unilateral weakness, numbness and vision impairment singly or in various combinations. The National Stroke Association lists six major symptoms of acute stroke with disorders of higher cortical function (HCF) poorly represented in these major categories Aim: The frequency of impaired cortical function with and without elementary neurological syndromes of motor and sensory impairment in three hospital based stroke registries, Patient population: Retrospective mini metanalysis of three large stroke registries N INDS (n=1805). DSDB (n=1281), Kentucky Stroke Registry (KYSR) (n=4715). Methods: The three most common behavioural syndromes representing large scale cognitive networks (aphasias and neglect syndromes) and regional (apraxias) were analysed as to their frequencies with and without accompanying sensorimotor deficits. Patients who had suppressed consciousness were excluded. Behavioural syndromes were predefined in all data banks Results: Range of HCF frequencies were21-37%, The individual registries were NiNDS: 310/120 (25.7%), DSDB 434/1170 (37 1%) and KYSR 1037/4715 (21.9%). Comparison of HCF with and without sensorimotor deficits revealed were significant in all three registries, Conclusion: Diverse cultural and linguistic backgrounds may not be associated with unique patterns of brain development. HCF are frequent in stroke and in a significant proportion of stroke patients cognitive impairment is the sole presenting neurological deficit. This necessitates a systematic higher cortical function appraisal. This is the first report of combined stroke registry data taken from multinational, multilingual and multiracial sources.