Adjunctive use of controlled‐release pregabalin in adults with treatment‐resistant partial seizures: A double‐blind, randomized, placebo‐controlled trial. Issue 8 (24th June 2014)

• Record Type: Journal Article
• Authors: French, Jacqueline; Brandt, Christian; Friedman, Daniel; Biton, Victor; Knapp, Lloyd; Pitman, Verne; Chew, Marci; Dubrava, Sarah; Posner, Holly B.
• Is Part Of: Epilepsia. Volume 55:Issue 8(2014:Aug.)
• Page Start: 1220
• Page End: 1228
• Publication Date: 2014-06-24
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12690
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi12690-abs-0001"> <title>Summary</title> <sec id="epi12690-sec-0001" sec-type="section"> <title>Objectives</title> <p>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).</p> </sec> <sec id="epi12690-sec-0002" sec-type="section"> <title>Methods</title> <p>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<sub>e</sub>‐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.</p> </sec> <sec id="epi12690-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="epi12690-sec-0004" sec-type="section"> <title>Significance</title> <p>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.</p> <p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <ext-link ext-link-type="uri" xlink:href="http://onlinelibrary.wiley.com/doi/10.1111/epi.12690/suppinfo" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">here</ext-link>.</p> </sec> </abstract>