title: Prototype antiepileptic drug clinical development plan.
abstract: Antiepileptic drug (AED) development has been generally difficult owing to many factors: regulatory requirements for demonstration of efficacy and safety, subject availability, traditional trial designs, and physicians' beliefs about epilepsy and its treatment. The U.S. Food and Drug Administration (FDA) regulations require a new drug to be shown safe and effective for its intended use before it can be marketed. The unambiguous proof required is a formidable hurdle for AED development. We report a recent clinical development plan highlighting innovations in clinical trial design that have addressed these requirements, discuss alternative endpoints, and compare the results of various trial designs at various stages of development. This model clinical development plan includes trials relevant to all three clinically relevant contexts in which an AED might be used: as an adjunct to an existing regimen, as a substitution for much of an existing AED regimen, and as monotherapy.
authors.affiliation: R. W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477.
authors.forename: L D
authors.initials: LD
authors.lastname: Kramer
authors.forename: G W
authors.initials: GW
authors.lastname: Pledger
authors.forename: M
authors.initials: M
authors.lastname: Kamin
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D017277:Drug Approval / Q000458:organization & administration; D004359:Drug Therapy, Combination; D015507:Drugs, Investigational / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy; D004832:Epilepsy, Absence / Q000188:drug therapy; D000078328:Felbamate; D006801:Humans; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000627:therapeutic use; D012107:Research Design / Q000592:standards*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000927:Anticonvulsants; D015507:Drugs, Investigational; D048448:Phenylcarbamates; D011409:Propylene Glycols; D000078328:Felbamate