Integrating disease progression models, non-clinical pharmacokinetic data and treatment response endpoints to optimize intravitreal dosing regimens.
Int J Clin Pharmacol Ther
; 52(7): 574-86, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24755127
ABSTRACT
OBJECTIVE:
To rapidly identify patients who will ultimately respond to 1 year of therapy, and optimize their inter dose interval. MATERIALS ANDMETHODS:
An intravitreal (IVT) ophthalmic dosing paradigm was designed based on clinical efficacy, nonclinical pharmacokinetics (PK), and disease progression modeling. Relevant non-clinical PK models were used to extrapolate IVT drug concentrations to patients.RESULTS:
Modeling predicted that > 80% of patients who would respond to 1 year of IVT treatment with an improvement in best-corrected visual acuity (BCVA) could be identified after the first 2 doses of treatment. These 2 initial doses produced ~ 75% of the maximum improvement in BCVA attainable. Moreover, the models also predicted those patients who responded after 1 year of treatment may tolerate an extension of the inter dose interval to 12 weeks without significant deterioration of BCVA. In contrast, > 70% of responsive patients who did not respond to 1 year of treatment showed inadequate responses after 2 doses.CONCLUSIONS:
These models use data from 2 doses to identify those patients likely to benefit after 1 year of treatment, and thereafter can lengthen their inter dose interval without deleterious effects. This method identifies potential treatment responders early, and lengthens the inter dose interval during long-term administration while allowing non-responders to pursue alternative therapies earlier, thereby minimizing risk to the patient.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fator A de Crescimento do Endotélio Vascular
/
Aptâmeros de Nucleotídeos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article