SAFETY AND SUSTAINED LONG-TERM EFFICACY OF PREGABALIN FOR PARTIAL-ONSET SEIZURES
Abstract number :
2.240
Submission category :
Year :
2003
Submission ID :
3905
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Ahmad Beydoun, Alan R. Kugler, Martha J. Greiner, Caroline M. Lee, Henning Anhut, Lloyd E. Knapp, Elizabeth A. Garofalo Department of Neurology, University of Michigan Hospital, Ann Arbor, MI; Pfizer Global Research and Development, Pfizer Inc, Ann Arbor,
Pregabalin is an alpha[sub]2[/sub]-delta ([alpha][sub]2[/sub]-[delta]) ligand that demonstrated significant efficacy as adjunctive therapy for partial-onset seizures in double-blind, randomized, placebo-control clinical trials. These analyses evaluate long-term efficacy and tolerability in a patient population with medically refractory epilepsy.
A total of 1480 patients participated in these open-label studies. These included 968 patients who elected to participate in the long-term extension phase of four double-blind trials and 512 subjects who were directly enrolled in the open-label phase of the trials ([italic]de novo[/italic] patients). Pregabalin was administered at dosages ranging from 75 to 600 mg/day, on either a BID or TID regimen, based on tolerability and efficacy. Treatment was continued as long as therapeutic response and tolerability were maintained. Evaluations consisted of the responder rate (percent of patients with [ge]50% reduction in seizure frequency compared with baseline; evaluable population defined as ITT with prospective baseline), percent change from baseline (evaluable), seizure freedom (ITT), and safety (ITT).
The longest pregabalin exposure was 4.8 years. Sixty-nine percent of pregabalin dosing (exposure) was [ge]450 mg/day. The overall responder rate was 35%. Among the 2-year cohort (n=220) the responder rate was 52%. Over the total open-label period, 59% of patients had at least a 25% improvement in seizure frequency and 14% had at least a 75% improvement. At the last observation, 8% of patients were seizure-free for [ge]6 months. Most adverse effects were of mild to moderate severity. The most common events were dizziness (33%) and somnolence (27%). A total of 185 patients (13%) withdrew from the study due to adverse events, of which 154 (10%) were considered treatment related. Serious treatment associated AEs occurred in 1% of patients. No new safety concerns were identified in this long-term study population.
This study shows that pregabalin administered in dosages of 75 to 600 mg/day is both safe and efficacious as long-term adjunctive therapy in patients with partial-onset seizures.
[Supported by: Pfizer Global Research and Development.]