First-in-Man Study With Inclacumab, a Human Monoclonal Antibody Against P-selectin.
J Cardiovasc Pharmacol
; 65(6): 611-9, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25714598
ABSTRACT
Inclacumab, a novel monoclonal antibody against P-selectin in development for the treatment and prevention of atherosclerotic cardiovascular diseases, was administered in an ascending single-dose study as intravenous infusion to evaluate safety, pharmacokinetics, and pharmacodynamics. Fifty-six healthy subjects were enrolled in this randomized, double-blind placebo-controlled study. Each dose level (0.03-20 mg/kg) was investigated in separate groups of 8 subjects (6 on inclacumab, 2 on placebo). Platelet-leukocyte aggregates, free/total soluble P-selectin concentration ratio, drug concentrations, bleeding time, platelet aggregation, antibody formation, and routine laboratory parameters were measured frequently until 32 weeks. Pharmacokinetic profiles were indicative of target-mediated drug disposition. Platelet-leukocyte aggregate inhibition and soluble P-selectin occupancy showed dose dependency and were strongly correlated to inclacumab plasma concentrations, with IC50 of 740 and 4600 ng/mL, respectively. Inclacumab was well tolerated by the majority of subjects and did neither affect bleeding time nor platelet aggregation. These findings allowed the investigation of the potential beneficial therapeutic use of inclacumab in patient study.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Cardiovasculares
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Selectina-P
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Anticorpos Monoclonais
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Cardiovasc Pharmacol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Suíça