Abstracts

RATIONALE: Pregabalin is an alpha[sub]2[/sub]-delta ([alpha][sub]2[/sub][delta]) ligand that exhibits analgesic, anxiolytic, and anticonvulsant activity. A double-blind, placebo-controlled, 41-center trial has demonstrated the efficacy, tolerability, and safety of adjunctive treatment with pregabalin in patients with medically refractory partial epilepsy. This current study reports the long-term efficacy and tolerability of pregabalin.
METHODS: All consenting patients completing the double-blind trial (Study 1008-009) were immediately enrolled in an open-label extension study (Study 1008-010) allowing continued exposure to pregabalin. In addition, [italic]de novo[/italic] patients with medically refractory partial-onset seizures who fulfilled eligibility criteria were directly enrolled into the open-label study. During the open-label phase, adjunctive treatment with pregabalin was optimized via flexible titration of doses up to 600 mg/day. Patients who took at least one dose of pregabalin during open-label were included in the intent-to-treat population (ITT). Patients who completed the double-blind study, took at least one open-label dose of pregabalin, and provided prospective baseline and open-label seizure diary data were considered evaluable patients for efficacy analyses. The efficacy of those patients who remained in the study for at least one year was evaluated by both the responder rate (defined as the percentage of patients with a [gte]50% reduction in seizure frequency during open-label treatment compared to baseline) and by the percent change from baseline in seizure frequency.
RESULTS: Of the 454 patients who participated in the study, 257 (57%) were evaluable for efficacy analyses and 195 (43%) were [italic]de novo[/italic]. Of all evaluable patients, 170 were exposed to pregabalin for at least 1 year and followed as a cohort. The mean patient age was 38.8 years (range: 15-82 years) with a mean duration of epilepsy of 26 years. Study patients presented with highly refractory epilepsy as evidenced by their mean and median prospective baseline seizure rates of 24.4 and 11.2 seizures/month, respectively, and that approximately 27% of the patients were taking 1, 45% taking 2, and 28% taking 3 or more concurrent AEDs at entry to open-label. Responder rates calculated over 84-day periods in the first year of open-label ranged from 47-52% for the 1-year cohort, and 38-51% for evaluable patients. Median percent change from baseline also calculated over 84-day periods in the first year of open-label ranged from 46-51% for the 1-year cohort, and 39-50% for the evaluable group. The most frequent adverse events were generally CNS related and mild to moderate in intensity. Serious adverse events were infrequent. The maximum patient exposure was 166 weeks for ITT patients. Approximately 50% of pregabalin patient-day exposure occurred at 600 mg/day, indicating continued tolerability and benefit at higher doses of pregabalin.
CONCLUSIONS: Long-term add-on therapy with pregabalin is safe and well-tolerated in patients with refractory partial seizures, with half of pregabalin exposure at 600 mg/day. The efficacy of pregabalin is sustained with no evidence for the development of tolerance after one year of treatment.
[Supported by: Pfizer Global Research and Development]; (Disclosure: Salary - Pfizer, Grant - Pfizer, Equity - Pfizer, Consulting - Pfizer, Ownership - Pfizer, Materials - Pfizer, Stock - Pfizer, Royalties - Pfizer, Honoraria - Pfizer, Other - Pfizer)