Abstracts

Pregabalin (PGB), a CNS-active compound, has demonstrated efficacy in clinical trials as adjunctive treatment for partial seizures with/without secondary generalizations. Using results from fixed-dose arms of 4 clinical trials, we characterized the duration and intensity of adverse events (AEs) that have been reported by patients (pts) receiving PGB as adjunctive treatment for partial seizures. The duration and intensity of AEs were examined in four 12-week, double-blind, placebo-controlled trials. 1174 pts with epilepsy refractory to treatment were randomized to fixed-dose treatment (367 received PBO; 86, 99, 90, 329, and 203 received PGB 150mg/d(BID), 150mg/d(TID), 300mg/d(BID), 600mg/d(BID), and 600mg/d(TID), respectively). AEs were collected daily. AE incidences were counted once per patient at first onset week. Recurring AEs were included in subsequent week(s). 89% of pts were white, 50.1% female, and 74% were taking [ge]2 concomitant AEDs. Patients had epilepsy for approximately 25 yrs with median seizure rate of 9.5 seizures/28-days at baseline. Across all 4 trials, treatment-associated AEs were generally mild-moderate and transient as they tended to resolve with continued treatment. Dizziness, somnolence, ataxia, and asthenia were the 4 most common AEs. After week one of treatment, 11.6%, 3%, 25.6%, 27.7%, and 10.3% of PGB pts receiving 150(BID), 150(TID), 300(BID), 600(BID), and 600(TID) mg/d, respectively, experienced dizziness vs 3% of PBO pts. By week 2, the incidence of dizziness dropped to an across-dose average of 2.7%. From weeks 2[ndash]12, 0.5%, 1.0%, 0.9%, 1.6%, and 0.6% of PGB pts on 150(BID), 150(TID), 300(BID), 600(BID), and 600(TID) reported dizziness (mean/wk) suggesting that most pts experienced this AE during week one of treatment. Similarly, by week one, 15.1%, 2%, 13.3%, 14.3%, and 6.4% of PGB pts on 150(BID), 150(TID), 300(BID), 600(BID), and 600(TID) mg/d experienced somnolence. By week two, the incidence of somnolence on PBG pts dropped to an across-dose average of 2.1%. From weeks 2[ndash]12, 0.2%, 0.1%, 0.5%, 0.8%, and 0.4% of PGB pts on 150(BID), 150(TID), 300(BID), 600(BID), and 600(TID) mg/d reported somnolence (mean/wk), again suggesting that most pts experienced the AE during the first week of treatment. Similar temporal patterns were observed for ataxia, asthenia, and all other AEs occurring in [ge]5% of pts. AE intensity did not affect AE duration. PGB pts who discontinued due to dizziness, ataxia, somnolence, and asthenia had incidence rates of 9.5%, 5.8%, 5.3% and 3.2% respectively, versus [le]1.1% for PBO dropouts due to the same AEs over the entire course of the trials with the majority discontinuing by week one. These findings suggest that pregabalin is well-tolerated and that the AEs experienced by some pts receiving PGB treatment are mild-moderate, occur at initiation of treatment, and tend to be transient in nature. (Supported by Pfizer Inc.)