{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T10:37:34Z","timestamp":1764239854663,"version":"3.37.3"},"reference-count":14,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,6,25]],"date-time":"2014-06-25T00:00:00Z","timestamp":1403654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Pfizer, Inc.","award":["B4511001"],"award-info":[{"award-number":["B4511001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Part 1 of this phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> study was a randomized, double\u2010blind, parallel\u2010group, placebo\u2010controlled, multicenter study of caregiver administered diazepam auto\u2010injector (<jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content>) in subjects with acute repetitive seizures (<jats:styled-content style=\"fixed-case\">ARS<\/jats:styled-content>) and demonstrated that diazepam <jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content> was well\u2010tolerated and significantly more effective than placebo <jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content> in delaying the time to next seizure or rescue. Part 2 of this study, presented herein, was an open\u2010label continuation to assess the long\u2010term safety and effectiveness of diazepam <jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content> for the treatment of <jats:styled-content style=\"fixed-case\">ARS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Of the 234 subjects randomized in part 1, 161 continued into part 2 and were provided open\u2010label diazepam <jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content>. Effectiveness measures were time to next seizure or rescue, number of subsequent rescues by type (rescue medication, emergency room visit, or other medical care), and number of subsequent seizures during the 12\u2010h follow\u2010up period. Safety data (adverse events and respirations &lt;8\/min) were also collected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During the open\u2010label part 2 study, 129 subjects were administered a total of 1,380 diazepam <jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content> treatments (median 4.5; range 1\u2013118), of which 1,071 (77.6%) were effective with no subsequent seizure or rescue during the 12\u2010h follow\u2010up period. Median number of subsequent seizures experienced by subjects was one (range 0\u201320). Of the 1,380 administrations, 79 (5.7%) required use of rescue medication, 18 (1.3%) required a visit to an emergency room, and 6 (0.4%) required other rescue medical care. In most (75%) of subjects with treatment\u2010emergent adverse events (<jats:styled-content style=\"fixed-case\">TEAEs<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s were mild or moderate in severity. Commonly reported treatment\u2010related <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s were injection\u2010site pain (10.9%), injection\u2010site hemorrhage (7%), and injection\u2010site bruising (6.3%). Although three subjects met the predefined respiratory rate threshold, none were considered clinically significant or reported as <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Long\u2010term treatment with diazepam <jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content> administered by trained caregivers in an outpatient setting to treat <jats:styled-content style=\"fixed-case\">ARS<\/jats:styled-content> is a safe and effective option.<\/jats:p><jats:p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/epi.12685\/supinfo\">here<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12685","type":"journal-article","created":{"date-parts":[[2014,6,25]],"date-time":"2014-06-25T19:32:04Z","timestamp":1403724724000},"page":"1444-1451","source":"Crossref","is-referenced-by-count":22,"title":["Safety and effectiveness of long\u2010term treatment with diazepam auto\u2010injector administered by caregivers in an outpatient setting for the treatment of acute repetitive seizures"],"prefix":"10.1111","volume":"55","author":[{"given":"Joanne","family":"Rogin","sequence":"first","affiliation":[{"name":"Minneapolis Clinic of Neurology Midwest Center for Seizure Disorders Golden Valley Minnesota U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Wheless","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center and Le Bonheur Children's Hospital Memphis Tennessee U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bassel","family":"Abou\u2010Khalil","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Nashville Tennessee U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin D.","family":"Wolter","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. New York New York U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn C.","family":"Pixton","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. Durham North Carolina U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy A.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. New York New York U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh B.","family":"Shukla","sequence":"additional","affiliation":[{"name":"Meridian Medical Technologies, Inc. Columbia Maryland U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl L.","family":"Roland","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. Durham North Carolina U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth W.","family":"Sommerville","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. 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