{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:33:30Z","timestamp":1768293210836,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T00:00:00Z","timestamp":1621123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Generalized tonic\u2010clonic (GTC) seizures are the most common type of generalized seizure and more common in children than adults. This phase 3 study evaluated the efficacy and safety of pregabalin for GTC seizures in adults and children with epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This randomized, double\u2010blind, multicenter study evaluated pregabalin (5\u00a0mg\/kg\/day or 10\u00a0mg\/kg\/day) vs placebo as adjunctive therapy for 10\u00a0weeks (following a 2\u2010week dose escalation), in pediatric and adult patients (aged 5\u201065\u00a0years) with GTC seizures. Primary endpoint was change in log\u2010transformed 28\u2010day seizure rate during active treatment. Secondary endpoints included responder rates, defined as proportion of patients with \u226550% reduction in 28\u2010day GTC seizure rate from baseline. Safety was monitored throughout.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 219 patients, 75, 72, and 72 were randomized to adjunctive pregabalin 5\u00a0mg\/kg\/day, 10\u00a0mg\/kg\/day, and placebo, respectively. Fifteen, 11, and 6 patients discontinued from the 5\u00a0mg\/kg\/day, 10\u00a0mg\/kg\/day, and placebo arms, respectively, most commonly due to adverse events (AEs; 10.7%, 6.9%, and 5.6%, respectively). A nonsignificant change in log\u2010transformed mean 28\u2010day seizure rate was seen with pregabalin 10\u00a0mg\/kg\/day vs placebo (least\u2010squares [LS] mean difference \u20130.01 [95% confidence interval (CI) \u20130.19 to 0.16]; <jats:italic>P\u00a0=<\/jats:italic>\u00a0.8889) and with pregabalin 5\u00a0mg\/kg\/day vs placebo (LS mean difference 0.02 [CI \u20130.15 to 0.19]; <jats:italic>P\u00a0=<\/jats:italic>\u00a0.8121). Similar observations were noted for adults and children. No significant differences were seen for secondary endpoints with pregabalin vs placebo, including responder rate. The most common AEs (\u226510%) were dizziness, headache, and somnolence. Most were of mild\/moderate intensity. Seven patients had serious AEs, with one death in the placebo arm (sudden unexpected death in epilepsy).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Adjunctive pregabalin treatment did not change GTC seizure rate in adults or children. The safety profile of pregabalin was similar to that known; treatment was well tolerated with few discontinuations due to AEs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12492","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T05:30:52Z","timestamp":1620106252000},"page":"381-393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pregabalin as adjunctive therapy in adult and pediatric patients with generalized tonic\u2010clonic seizures: A randomized, placebo\u2010controlled trial"],"prefix":"10.1002","volume":"6","author":[{"given":"Joseph","family":"Driscoll","sequence":"first","affiliation":[{"name":"Pfizer Inc Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Almas","sequence":"additional","affiliation":[{"name":"Pfizer Inc New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Gregorian","sequence":"additional","affiliation":[{"name":"Pfizer Inc Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alla","family":"Kyrychenko","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Dnipro Medical Institute of Conventional and Alternative Medicine Dnipro Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iryna","family":"Makedonska","sequence":"additional","affiliation":[{"name":"Dnipro City Children\u2019s Clinical Hospital #5 of Dnipro City Council Dnipro Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Pfizer Inc Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Patrick","sequence":"additional","affiliation":[{"name":"Pfizer Inc Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Scavone","sequence":"additional","affiliation":[{"name":"Pfizer Inc Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremias","family":"Antinew","sequence":"additional","affiliation":[{"name":"Pfizer Inc Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the 1105 Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,16]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization. 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