Adjunctive use of controlled-release pregabalin in adults with treatment-resistant partial seizures: A double-blind, randomized, placebo-controlled trial

作者：French Jacqueline^*; Brandt Christian; Friedman Daniel; Biton Victor; Knapp Lloyd; Pitman Verne; Chew Marci; Dubrava Sarah; Posner Holly B

来源：Epilepsia, 2014, 55(8): 1220-1228.

DOI：10.1111/epi.12690

• Epilepsy
• Clinical
• Lyrica
• Pregabalin
• Controlled-release
• Extended-release

Objectives: To assess the efficacy and tolerability of add-on pregabalin controlled-release formulation (PGB-CR) (doses of 165 or 330 mg/day) in patients with partial-onset seizures (POS).
Methods: This was a randomized, double-blind (DB), parallel-group study of PGB-CR once-daily as adjunctive treatment in adults with treatment-resistant partial seizures. After an 8-week baseline period, eligible patients were randomized (1: 1: 1) to placebo, PGB-CR 165 mg, or PGB-CR 330 mg for 14 weeks, including a 2-week dose escalation. Primary endpoint was the log(e)-transformed 28-day seizure rate for all POS with observable component during the full 14-week double-blind treatment phase. Secondary endpoints included the 50% responder rate and percent change from baseline in 28-day POS rate.
Results: Three hundred twenty-three patients were randomized and received treatment; placebo (n = 110), PGB-CR 330 mg (n = 100), PGB-CR 165 mg (n = 113); and 287 (88.9%) completed the trial. The primary efficacy analysis result, expressed as percent reduction from placebo, was 13.1% and 1.0% for PGB-CR 330 mg and PGB-CR 165 mg, respectively, and was not statistically significant (p = 0.091, 0.908). The proportion of 50% responders was similar for placebo (35.8%) and 165 mg PGB-CR (37.8%) and nominally higher for 330 mg PGB-CR (45.9%, p = 0.125 compared to placebo). The LS mean estimates of the percent change from baseline for placebo (-5.7%) was nominally smaller than 165 mg PGB-CR (-15.0%, p = 0.540) and 330 mg PGB-CR (-31.5%, p = 0.079); however, the median percent changes from baseline were not as well differentiated (placebo, -35.4%; 165 mg PGB-CR, -38.0%; 330 mg PGB-CR -43.4%). Rates of adverse events (AEs) were low for placebo and study drug; the most frequent reported AEs were dizziness, somnolence, and fatigue, consistent with the immediate-release formulation.
Significance: Results from this trial did not demonstrate that PGB-CR is effective in reducing seizure frequency below that of placebo. Both doses of PGB-CR were shown to be safe and well-tolerated.

• 出版日期2014-8