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

Epilepsia. 2014 Aug;55(8):1220-8. doi: 10.1111/epi.12690. Epub 2014 Jun 24.


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 loge -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.

Trial registration: NCT01262677.

Keywords: Clinical; Controlled-release; Epilepsy; Extended-release; Lyrica; Pregabalin.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / administration & dosage*
  • Delayed-Action Preparations / administration & dosage
  • Double-Blind Method
  • Drug Therapy, Combination
  • Epilepsies, Partial / diagnosis*
  • Epilepsies, Partial / drug therapy*
  • Epilepsies, Partial / physiopathology
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Pregabalin
  • Prospective Studies
  • Treatment Outcome
  • Young Adult
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / analogs & derivatives*


  • Anticonvulsants
  • Delayed-Action Preparations
  • Pregabalin
  • gamma-Aminobutyric Acid

Associated data