TY - JOUR
T1 - Pregabalin adjunctive therapy for focal onset seizures in children 1 month to <4 years of age
T2 - A double-blind, placebo-controlled, video-electroencephalographic trial
AU - the A0081042 study group
AU - Mann, Donald
AU - Antinew, Jeremias
AU - Knapp, Lloyd
AU - Almas, Mary
AU - Liu, Jing
AU - Scavone, Joseph
AU - Yang, Ruoyong
AU - Modequillo, Margaret
AU - Makedonska, Iryna
AU - Ortiz, Marilyn
AU - Kyrychenko, Alla
AU - Nordli, Douglas
AU - Farkas, Viktor
AU - Farkas, Mark Kristof
AU - Shalkevich, Leanid
AU - Jansen, Anna
AU - Ivanov, Ivan
AU - Nedkova, Vania
AU - Fang, Fang
AU - Wang, Yi
AU - Pinard, Jean Marc
AU - Brandl, Ulrich
AU - Zafeiriou, Dimitrios
AU - Altmann, Anna
AU - Berenyi, Marianne
AU - Bessenyei, Monika
AU - Fogaras, Andras
AU - Szabo, Geza
AU - Fattal-Valevski, Aviva
AU - Kim, Ki Joong
AU - Beydoun, Ahmad
AU - Hmaimess, Ghassan
AU - Yahaya, Nor Azni
AU - Barlaan-Lukban, Marissa
AU - Bolanos, Martha
AU - De la Calzada, Jo Janette
AU - Estrella Ibe, Maria
AU - Valencia, Maria Antonia Aurora
AU - Craiu, Dana
AU - Diaconu, Georgeta
AU - Antonova, Tatiana
AU - Belousova, Elena
AU - Karakulova, Yulia
AU - Khaletskaya, Olga
AU - Lvova, Olga
AU - Strachunskaya, Maria
AU - Kravljanac, Ruzica
AU - Nikolic, Dimitrije
AU - Lopez Pison, Francisco
AU - Chang, Ying Chao
N1 - Publisher Copyright:
Wiley Periodicals, Inc. © 2020 International League Against Epilepsy
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Objective: To evaluate the efficacy and safety of pregabalin as adjunctive treatment for children (aged 1 month-<4 years) with focal onset seizures (FOS) using video-electroencephalography (V-EEG). Methods: This randomized, placebo-controlled, international study included V-EEG seizure monitoring (48-72 hours) at baseline and over the last 3 days of 14-day (5-day dose escalation; 9-day fixed dose) double-blind pregabalin treatment (7 or 14 mg/kg/d in three divided doses). This was followed by a double-blind 1-week taper. The primary efficacy endpoint was log-transformed seizure rate (loge[24-hour seizure rate + 1]) for all FOS recorded during the double-blind V-EEG monitoring, evaluated in subjects who took ≥1 dose of study medication, experienced ≥1 baseline seizure(s), and had a treatment phase V-EEG. Safety and tolerability were assessed by adverse events (AEs), clinical laboratory data, physical/neurological examinations, vital signs, and electrocardiograms. Results: Overall, 175 patients were randomized (mean age = 28.2 months; 59% male, 69% white, 30% Asian) in a 2:1:2 ratio to pregabalin 7 or 14 mg/kg/d (n = 71 or n = 34, respectively), or placebo (n = 70). Pregabalin 14 mg/kg/d (n = 28) resulted in a statistically significant 35% reduction of loge(24-hour seizure rate + 1) versus placebo (n = 53; P =.022), an effect that was not observed with pregabalin 7 mg/kg/d (n = 59; P =.461). The most frequently reported treatment-emergent AEs for pregabalin 7 mg/kg/d, 14 mg/kg/d, and placebo, respectively, were somnolence (11.3%, 17.6%, and 5.7%) and upper respiratory tract infection (7.0%, 11.8%, and 11.4%). All AEs were mild to moderate in severity. Significance: Pregabalin 14 mg/kg/d (but not 7 mg/kg/d) significantly reduced seizure rate in children with FOS, when assessed using V-EEG, compared with placebo. Both pregabalin dosages were generally safe and well tolerated in children 1 month to <4 years of age with FOS. Safety and tolerability were consistent with the known profile of pregabalin in older children with epilepsy.
AB - Objective: To evaluate the efficacy and safety of pregabalin as adjunctive treatment for children (aged 1 month-<4 years) with focal onset seizures (FOS) using video-electroencephalography (V-EEG). Methods: This randomized, placebo-controlled, international study included V-EEG seizure monitoring (48-72 hours) at baseline and over the last 3 days of 14-day (5-day dose escalation; 9-day fixed dose) double-blind pregabalin treatment (7 or 14 mg/kg/d in three divided doses). This was followed by a double-blind 1-week taper. The primary efficacy endpoint was log-transformed seizure rate (loge[24-hour seizure rate + 1]) for all FOS recorded during the double-blind V-EEG monitoring, evaluated in subjects who took ≥1 dose of study medication, experienced ≥1 baseline seizure(s), and had a treatment phase V-EEG. Safety and tolerability were assessed by adverse events (AEs), clinical laboratory data, physical/neurological examinations, vital signs, and electrocardiograms. Results: Overall, 175 patients were randomized (mean age = 28.2 months; 59% male, 69% white, 30% Asian) in a 2:1:2 ratio to pregabalin 7 or 14 mg/kg/d (n = 71 or n = 34, respectively), or placebo (n = 70). Pregabalin 14 mg/kg/d (n = 28) resulted in a statistically significant 35% reduction of loge(24-hour seizure rate + 1) versus placebo (n = 53; P =.022), an effect that was not observed with pregabalin 7 mg/kg/d (n = 59; P =.461). The most frequently reported treatment-emergent AEs for pregabalin 7 mg/kg/d, 14 mg/kg/d, and placebo, respectively, were somnolence (11.3%, 17.6%, and 5.7%) and upper respiratory tract infection (7.0%, 11.8%, and 11.4%). All AEs were mild to moderate in severity. Significance: Pregabalin 14 mg/kg/d (but not 7 mg/kg/d) significantly reduced seizure rate in children with FOS, when assessed using V-EEG, compared with placebo. Both pregabalin dosages were generally safe and well tolerated in children 1 month to <4 years of age with FOS. Safety and tolerability were consistent with the known profile of pregabalin in older children with epilepsy.
KW - children
KW - focal onset seizures
KW - pediatric
KW - pregabalin
UR - http://www.scopus.com/inward/record.url?scp=85081973277&partnerID=8YFLogxK
U2 - 10.1111/epi.16466
DO - 10.1111/epi.16466
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C2 - 32189338
AN - SCOPUS:85081973277
SN - 0013-9580
VL - 61
SP - 617
EP - 626
JO - Epilepsia
JF - Epilepsia
IS - 4
ER -