Neurocognitive effects of adjunctive levetiracetam in children with partial-onset seizures: a randomized, double-blind, placebo-controlled, noninferiority trial
Paul M Levisohn, Mark Mintz, Scott J Hunter, Haichen Yang, John Jones, N01103 Levetiracetam Study Group, Ricardo Ayala, Pamela Cooper, Ronald Davis, Vivian Faircloth, Jose Ferreira, Sarah Finnegan, Matthew L Frank, David Griesemer, Ajay Gupta, Angel Hernandez, Lydia Kernitsky, John F Kerrigan, Sookyong Koh, Wayne Langburt, Edwin Liu, Wendy Mitchell, Shiva Natarajan, Larry Olsen, David B Owen, Maria Sam, Paul Sandor, Nirupa Shah, Izelle Smuts, Doris Trauner, Adri van der Walt, William Zinser, Ralph Agard, Roberta Berger, Heather Bradley Paniucki, Vicki Brewer, Virdette L Brumm, Venera Bruto, Veronica Clement, James P Culbert, Kim Cunningham, Donna Lynn Flowers, Marsha Gabriel, Patrick Gorman, Ann Green, Mark Gunther, Jennifer Haut, Alcuin Johnson, Dan LeGoff, Susan Dickerson Mayes, Joan Naini, Sharon Nichols, George Prigatano, Mike Sherman, Karen Smith, Robin Stephens, Noline-Ann Strydom, Virginia L Van de Water, Mark T Wagner, Greta Wilkening, Frank Zelko, Jennifer Stewart, Paul M Levisohn, Mark Mintz, Scott J Hunter, Haichen Yang, John Jones, N01103 Levetiracetam Study Group, Ricardo Ayala, Pamela Cooper, Ronald Davis, Vivian Faircloth, Jose Ferreira, Sarah Finnegan, Matthew L Frank, David Griesemer, Ajay Gupta, Angel Hernandez, Lydia Kernitsky, John F Kerrigan, Sookyong Koh, Wayne Langburt, Edwin Liu, Wendy Mitchell, Shiva Natarajan, Larry Olsen, David B Owen, Maria Sam, Paul Sandor, Nirupa Shah, Izelle Smuts, Doris Trauner, Adri van der Walt, William Zinser, Ralph Agard, Roberta Berger, Heather Bradley Paniucki, Vicki Brewer, Virdette L Brumm, Venera Bruto, Veronica Clement, James P Culbert, Kim Cunningham, Donna Lynn Flowers, Marsha Gabriel, Patrick Gorman, Ann Green, Mark Gunther, Jennifer Haut, Alcuin Johnson, Dan LeGoff, Susan Dickerson Mayes, Joan Naini, Sharon Nichols, George Prigatano, Mike Sherman, Karen Smith, Robin Stephens, Noline-Ann Strydom, Virginia L Van de Water, Mark T Wagner, Greta Wilkening, Frank Zelko, Jennifer Stewart
Abstract
Purpose: Evaluate potential neurocognitive effects of adjunctive levetiracetam in children with inadequately controlled partial-onset seizures (POS).
Methods: Randomized, double-blind, placebo-controlled, noninferiority safety study. Children (4-16 years; IQ > or =65) with > or =1 POS during 4 weeks before screening despite taking 1-2 antiepileptic drugs (AEDs) were randomized (2:1) to levetiracetam (20-60 mg/kg/day) or placebo for 12 weeks.
Results: Ninety-nine patients were randomized with 98 (levetiracetam 64, placebo 34) in intent-to-treat (ITT) and 73 (levetiracetam 46, placebo 27) in per protocol (PP) populations. Primary cognitive assessment was the Leiter International Performance Scale-Revised Attention and Memory Battery with the memory screen composite score change from baseline as the primary endpoint. PP Least Square Mean [LSM (standard error)] were 5.36 (1.78) for levetiracetam; 5.17 (2.33) for placebo; difference [two-sided 90% confidence interval (CI)] 0.19 (-4.69, 5.08). Levetiracetam was noninferior to placebo because the 90% CI lower bound was greater than the defined noninferiority margin (-9.0). There were no statistically significant differences between groups in Wide Range Assessment of Memory and Learning-2 indexes and Leiter-R Examiner's Rating Scale scores. Median reductions from baseline in weekly POS frequency were 91.5% versus 26.5% for levetiracetam versus placebo; > or =50% responder rates: 62.5% versus 41.2%; seizure freedom rates: 46.9% versus 8.8% (ITT). Adverse events were reported by 89.1% levetiracetam-treated and 85.3% placebo-treated patients; those reported by > or =10% levetiracetam patients and more often with levetiracetam were headache, nasopharyngitis, fatigue, vomiting, somnolence, and aggression.
Discussion: Neurocognitive effects were no different in pediatric patients with POS treated with adjunctive levetiracetam or placebo. Levetiracetam was effective and well tolerated.
Source: PubMed