Abstracts

Randomized controlled trials (RCT) rarely resemble behaviors in clinical practice. We compared the efficacy, tolerability, and AE profiles exhibited by pregabalin (PGB)[ndash]an [alpha][sub]2[/sub]-[delta] ligand with anticonvulsant, analgesic, and anxiolytic properties[ndash]administered using a flexible-dose regimen, similar to clinical practice, against profiles exhibited when using a fixed-dose regimen, commonly employed in RCTs. Data from two 12-week, placebo-controlled, double-blind, randomized, trials were used to identify differences in efficacy, tolerability and AE profiles observed when PGB is used as add-on therapy administered via fixed- and flexible-dose schedules. All randomized patients experienced refractory epilepsy and were on 1-3 anti-epileptic drugs (AEDs). In the fixed-dose group, patients were randomized to 1of 3 effective dosages of PGB: 150, 300, or 600mg/day (BID) or placebo (PBO). In the flexible-dose group, patients received: 150-600 mg/day PGB (BID) which was adjusted at regular intervals depending on treatment efficacy/tolerance; or PBO. The effect of dosing regimen on PGB anticonvulsant treatment was assessed using measurements of: seizure frequency (% change), incidence of patients experiencing a [ge]50% seizure-frequency reduction (responders), adverse events, and tolerability. A total of 794 patients were enrolled in both studies (PBO: 173; PGB: 621). The average patient suffered epilepsy for 25 years and experienced approximately 9 seizures/month (median) before PGB add-on treatment. Approximately, 75% of patients were on 2 or more concurrent AEDs. The primary population was intent-to-treat (ITT) defined as all patients randomized to treatment and who received at least one dose of study medication. All PGB treatment arms were superior to PBO. Patients receiving 600 mg/day PGB in both studies with a fixed-dose schedule experienced significant reductions in seizure frequency (fixed dose: 54% and 49% vs. flexible dose: 35%) versus PBO and significant increases in responder rates (fixed dose: 51% and 45% vs. flexible dose: 31%) versus PBO. The AE profiles were similar for both studies with most common AEs being: dizziness, somnolence, ataxia, asthenia and weight gain. PGB was well tolerated by all treatment groups, however, greater tolerability was exhibited by patients on the flexible-dose regimen as evidenced by discontinuation rates due to AEs (fixed dose: 23.6% and 32.8% vs. flexible dose: 12.2%). PGB is an effective and well-tolerated add-on treatment for patients with partial seizures. Patients receiving PGB via both fixed- or flexible-dose regimens benefited from significant reductions in seizure frequency. In addition, flexible-dosing provided improved tolerability. (Supported by Pfizer, Inc)