PMID- 32189338 OWN - NLM STAT- MEDLINE DCOM- 20201016 LR - 20201016 IS - 1528-1167 (Electronic) IS - 0013-9580 (Linking) VI - 61 IP - 4 DP - 2020 Apr TI - Pregabalin adjunctive therapy for focal onset seizures in children 1 month to <4 years of age: A double-blind, placebo-controlled, video-electroencephalographic trial. PG - 617-626 LID - 10.1111/epi.16466 [doi] 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 (log(e) [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 log(e) (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. CI - Wiley Periodicals, Inc. (c) 2020 International League Against Epilepsy. FAU - Mann, Donald AU - Mann D AUID- ORCID: 0000-0002-7692-7668 AD - Pfizer Global Research and Development, Groton, Connecticut. FAU - Antinew, Jeremias AU - Antinew J AD - Pfizer Global Research and Development, Groton, Connecticut. FAU - Knapp, Lloyd AU - Knapp L AD - Pfizer Global Research and Development, Groton, Connecticut. FAU - Almas, Mary AU - Almas M AD - Pfizer, New York, New York. FAU - Liu, Jing AU - Liu J AD - Pfizer Global Research and Development, Groton, Connecticut. FAU - Scavone, Joseph AU - Scavone J AD - Pfizer Global Research and Development, Groton, Connecticut. FAU - Yang, Ruoyong AU - Yang R AD - Pfizer Global Research and Development, Groton, Connecticut. FAU - Modequillo, Margaret AU - Modequillo M AD - Department of Pediatrics, Perpetual Succour Hospital, Cebu City, Philippines. FAU - Makedonska, Iryna AU - Makedonska I AD - Dnipro City Children's Clinical Hospital #5 of Dnipro City Council, Dnipro, Ukraine. FAU - Ortiz, Marilyn AU - Ortiz M AD - Child Neuroscience Division, Philippine Children's Medical Center, Quezon City, Philippines. FAU - Kyrychenko, Alla AU - Kyrychenko A AD - Department of Internal Medicine, Dnipro Medical Institute of Conventional and Alternative Medicine, Dnipro, Ukraine. FAU - Nordli, Douglas AU - Nordli D AD - Pediatric Neurology, University of Chicago Medicine, Chicago, Illinois. FAU - Farkas, Viktor AU - Farkas V AD - First Department of Pediatrics, Semmelweis University, Budapest, Hungary. FAU - Farkas, Mark Kristof AU - Farkas MK AD - First Department of Pediatrics, Semmelweis University, Budapest, Hungary. CN - A0081042 study group LA - eng SI - ClinicalTrials.gov/NCT02072824 GR - Pfizer/International PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200318 PL - United States TA - Epilepsia JT - Epilepsia JID - 2983306R RN - 0 (Anticonvulsants) RN - 55JG375S6M (Pregabalin) SB - IM MH - Anticonvulsants/*administration & dosage/adverse effects MH - Chemotherapy, Adjuvant/methods MH - Child, Preschool MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Therapy, Combination/methods MH - Electroencephalography MH - Epilepsies, Partial/*drug therapy MH - Female MH - Humans MH - Infant MH - Male MH - Pregabalin/*administration & dosage/adverse effects MH - Seizures/*drug therapy MH - Video Recording OTO - NOTNLM OT - children OT - focal onset seizures OT - pediatric OT - pregabalin FIR - Shalkevich, Leanid IR - Shalkevich L FIR - Jansen, Anna IR - Jansen A FIR - Ivanov, Ivan IR - Ivanov I FIR - Nedkova, Vania IR - Nedkova V FIR - Fang, Fang IR - Fang F FIR - Wang, Yi IR - Wang Y FIR - Pinard, Jean-Marc IR - Pinard JM FIR - Brandl, Ulrich IR - Brandl U FIR - Zafeiriou, Dimitrios IR - Zafeiriou D FIR - Altmann, Anna IR - Altmann A FIR - Berenyi, Marianne IR - Berenyi M FIR - Bessenyei, Monika IR - Bessenyei M FIR - Fogaras, Andras IR - Fogaras A FIR - Szabo, Geza IR - Szabo G FIR - Fattal-Valevski, Aviva IR - Fattal-Valevski A FIR - Kim, Ki Joong IR - Kim KJ FIR - Beydoun, Ahmad IR - Beydoun A FIR - Hmaimess, Ghassan IR - Hmaimess G FIR - Yahaya, Nor Azni IR - Yahaya NA FIR - Barlaan-Lukban, Marissa IR - Barlaan-Lukban M FIR - Bolanos, Martha IR - Bolanos M FIR - De la Calzada, Jo Janette IR - De la Calzada JJ FIR - Estrella Ibe, Maria IR - Estrella Ibe M FIR - Valencia, Maria Antonia Aurora IR - Valencia MAA FIR - Craiu, Dana IR - Craiu D FIR - Diaconu, Georgeta IR - Diaconu G FIR - Antonova, Tatiana IR - Antonova T FIR - Belousova, Elena IR - Belousova E FIR - Karakulova, Yulia IR - Karakulova Y FIR - Khaletskaya, Olga IR - Khaletskaya O FIR - Lvova, Olga IR - Lvova O FIR - Strachunskaya, Maria IR - Strachunskaya M FIR - Kravljanac, Ruzica IR - Kravljanac R FIR - Nikolic, Dimitrije IR - Nikolic D FIR - Lopez Pison, Francisco IR - Lopez Pison F FIR - Chang, Ying-Chao IR - Chang YC FIR - Chou, I-Ching IR - Chou IC FIR - Lee, Wang-Tso IR - Lee WT FIR - Nabangchang, Charcrin IR - Nabangchang C FIR - Sanmaneechai, Oranee IR - Sanmaneechai O FIR - Dundar, Nihal Olgac IR - Dundar NO FIR - Gencpinar, Pinar IR - Gencpinar P FIR - Chomolyak, Yurii IR - Chomolyak Y FIR - Delva, Dmytro IR - Delva D FIR - Martyniuk, Volodymyr IR - Martyniuk V FIR - Davis, Ronald IR - Davis R FIR - Ferreira, Jose IR - Ferreira J FIR - Tomasovic, Jerry IR - Tomasovic J EDAT- 2020/03/20 06:00 MHDA- 2020/10/21 06:00 CRDT- 2020/03/20 06:00 PHST- 2019/09/16 00:00 [received] PHST- 2020/02/12 00:00 [revised] PHST- 2020/02/12 00:00 [accepted] PHST- 2020/03/20 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2020/03/20 06:00 [entrez] AID - 10.1111/epi.16466 [doi] PST - ppublish SO - Epilepsia. 2020 Apr;61(4):617-626. doi: 10.1111/epi.16466. Epub 2020 Mar 18.