{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:48:06Z","timestamp":1794008886755,"version":"4.8.0"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T00:00:00Z","timestamp":1564358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To evaluate safety\u2010 and seizure\u2010related outcomes with repeated intermittent use of a novel formulation of midazolam administered as a single\u2010dose nasal spray (\n                      <jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>\n                      ) in the outpatient treatment of patients experiencing seizure clusters (\n                      <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>\n                      s).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this open\u2010label extension trial (ClinicalTrials.gov\n                      <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>\n                      01529034), patients aged \u226512\u00a0years and on a stable regimen of antiepileptic drugs who completed the original phase\n                      <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>\n                      , randomized controlled trial were enrolled. Caregivers administered\n                      <jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>\n                      5\u00a0mg when patients experienced\n                      <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>\n                      s; a second dose could be given if seizures did not terminate within 10\u00a0minutes or recurred within 10\u00a0minutes\u20106\u00a0hours. Patients were monitored for treatment\u2010emergent adverse events (\n                      <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>\n                      s) throughout, and the main seizure\u2010related outcome was treatment success, defined as seizure termination within 10\u00a0minutes and no recurrence 10\u00a0minutes\u20106\u00a0hours after drug administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 175 patients enrolled, 161 (92.0%) received \u22651\n                      <jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>\n                      dose, for a total of 1998\n                      <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>\n                      episodes. Median time spent by patients in the trial was 16.8\u00a0months (range = 1\u201055.7\u00a0months).\n                      <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>\n                      s were experienced by 40.4% of patients within 2\u00a0days of drug administration and 57.1% overall.\n                      <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>\n                      s reported by most patients (within 2\u00a0days and overall) were nasal discomfort (12.4%) and somnolence (9.3%). One patient each discontinued due to treatment\u2010related nasal discomfort and somnolence. There were no patients with treatment\u2010related respiratory depression, and none with\n                      <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>\n                      s indicative of drug abuse or dependence. Treatment success criteria were met in 55% (1108\/1998) of\n                      <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>\n                      episodes after administration of a single 5\u2010mg dose and in 80.2% (617\/769) with the second dose. Treatment success was consistent over treated episode number.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Repeated, intermittent, acute treatment of patients experiencing\n                      <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>\n                      s with\n                      <jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>\n                      in the outpatient setting was well tolerated over an extended period, with maintenance of efficacy suggesting lack of development of tolerance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.16300","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T03:28:55Z","timestamp":1564370935000},"page":"1809-1819","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open\u2010label extension trial"],"prefix":"10.1111","volume":"60","author":[{"given":"James W.","family":"Wheless","sequence":"first","affiliation":[{"name":"Le Bonheur Comprehensive Epilepsy Program &amp; Neuroscience Institute Le Bonheur Children's Hospital Memphis Tennessee"},{"name":"Pediatric Neurology University of Tennessee Health Science Center Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze\u2010Chiang","family":"Meng","sequence":"additional","affiliation":[{"name":"Proximagen Plymouth Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Van Ess","sequence":"additional","affiliation":[{"name":"Proximagen Plymouth Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Detyniecki","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale Comprehensive Epilepsy Center Yale School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Sequeira","sequence":"additional","affiliation":[{"name":"Proximagen Plymouth Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Pullman","sequence":"additional","affiliation":[{"name":"Proximagen Plymouth Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2017.04.016"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13465"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-007-0011-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000177"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.013"},{"key":"e_1_2_8_7_1","unstructured":"Valeant Pharmaceuticals.Diastat prescribing information. 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