UK-279,276, a neutrophil inhibitory glycoprotein, in acute stroke: tolerability and pharmacokinetics.
Stroke
; 34(7): 1704-9, 2003 Jul.
Article
em En
| MEDLINE
| ID: mdl-12805489
ABSTRACT
BACKGROUND AND PURPOSE:
UK-279,276, a recombinant glycoprotein, binds selectively to the CD11b/CD18 integrin on neutrophils and has the potential to modulate the neuroinflammation associated with acute stroke. After preclinical evidence of neuroprotection, UK-279,276 has entered clinical development. The purposes of this study were to evaluate the safety and tolerability of UK-279,276 and to examine its pharmacokinetics and pharmacodynamics (binding to neutrophil CD11b) in patients with acute stroke.METHODS:
This was a multicenter, double-blind, dose-escalation study in 176 patients randomized to a single intravenous dose of UK-279,276 (6 cohorts 0.06, 0.1, 0.2, 0.5, 1.0, 1.5 mg/kg) or placebo (31 randomization within each cohort) within 12 hours of stroke onset.RESULTS:
Age and stroke severity were well balanced across groups, with a mean age of 70 years (range, 39 to 92 years) and moderate baseline stroke severity (mean Scandinavian Stroke Scale score, 36.5 to 43.2; mean National Institutes of Health Stroke Scale score, 6.3 to 8.5). UK-279,276 was well tolerated at doses up to 1.5 mg/kg. There was no evidence of a relationship between dose of UK-279,276 and adverse events or clinical chemistry or hematology laboratory tests, or of an increased incidence of infection-related adverse events with the study drug. A dose-dependent UK-279,276-specific IgG antibody response was observed in patients treated with the 1.0- and 1.5-mg/kg doses. UK-279,276 displayed nonlinear pharmacokinetics across the dose range investigated. The duration of CD11b saturation was dose dependent, with >80% saturation achieved for at least 7 days after treatment with UK-279,276 1.0 and 1.5 mg/kg.CONCLUSIONS:
UK-279,276 was well tolerated in acute stroke patients at single doses up to 1.5 mg/kg. Further clinical investigation of UK-279,276 is ongoing.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas
/
Proteínas de Helminto
/
Fármacos Neuroprotetores
/
Acidente Vascular Cerebral
/
Proteínas de Membrana
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
Limite:
Aged80
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article