{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:36:08Z","timestamp":1787016968944,"version":"build-2736575974"},"reference-count":29,"publisher":"BMJ","issue":"10","funder":[{"name":"This work was supported by Ferrer Internacional S.A."}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2018,3,1]]},"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>There is a need for fast-acting, non-injection antiagitation treatments that are well tolerated and can be used outside of healthcare facilities. In phase II\/III trials, an inhaled formulation of loxapine (ADASUVE\u00ae), a well-established, first-generation antipsychotic agent, provided rapid control of mild to moderate agitation in the hospital setting. The present study was designed to investigate the safety and efficacy of inhaled loxapine when self-administered outside the hospital setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This phase IV, multicentre, single-arm, open-label clinical trial is being conducted in five countries in Europe: Spain, Germany, Norway, Romania and Austria. The aim is to include approximately 500 patients with schizophrenia or bipolar disorder who previously received and responded well to inhaled loxapine in the hospital setting. Eligible patients will be followed up for 6 months from baseline. They will be given a 10\u2009mg dose of inhaled loxapine to self-administer outside the hospital setting to treat an agitation episode, should one occur. Patients will also be given a short-acting beta-agonist bronchodilator for treatment of possible severe respiratory side effects. The primary endpoint is incidence of serious adverse events (AEs) and respiratory AEs of special interest related to use of inhaled loxapine outside the hospital setting. Secondary endpoints include incidence of other AEs, Clinical Global Impression-Improvement scores up to 2\u2009hours after self-administration of inhaled loxapine, time to improvement of agitation, patient satisfaction with treatment, treatment outcomes according to agitation severity and concordance between the patient (or a family member\/caregiver) and the physician in scoring of agitation severity and the decision to self-administer inhaled loxapine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The protocol received ethics committee approval in the participating countries between January and August 2016. The results of this study will be disseminated through one or more scientific papers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      EudraCT2015-003331-36;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"NCT02525991\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\">NCT02525991<\/jats:ext-link>\n                      ; Pre-results.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2017-020242","type":"journal-article","created":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T00:59:33Z","timestamp":1538528373000},"page":"e020242","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Safety and efficacy of self-administered inhaled loxapine (ADASUVE) in agitated patients outside the hospital setting: protocol for a phase IV, single-arm, open-label trial"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct02525991","registry":"10.18810\/clinical-trials-gov","type":"preResults"}],"author":[{"given":"Emilio","family":"Gil","sequence":"first","affiliation":[{"name":"Medical Department, Ferrer Internacional, S.A., Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Garcia- Alonso","sequence":"additional","affiliation":[{"name":"Medical Department, Ferrer Internacional, S.A., Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Boldeanu","sequence":"additional","affiliation":[{"name":"Medical Department, Ferrer Internacional, S.A., Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tha\u00efs","family":"Baleeiro Teixeira","sequence":"additional","affiliation":[{"name":"Medical Department, Ferrer Internacional, S.A., Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,10,2]]},"reference":[{"key":"2025121514141398000_8.10.e020242.1","doi-asserted-by":"publisher","DOI":"10.1080\/10673220127892"},{"key":"2025121514141398000_8.10.e020242.2","first-page":"3","article-title":"Treatment of agitation in bipolar disorder across the life cycle","volume":"64","author":"Alderfer","year":"2003","journal-title":"J Clin Psychiatry"},{"key":"2025121514141398000_8.10.e020242.3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1092852900026146","article-title":"The treatment of acute agitation in schizophrenia","volume":"12","author":"Battaglia","year":"2007","journal-title":"CNS Spectr"},{"key":"2025121514141398000_8.10.e020242.4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2174\/1745017901612010075","article-title":"State of acute agitation at psychiatric emergencies in europe: the stage study","volume":"12","author":"San","year":"2016","journal-title":"Clin Pract Epidemiol Ment Health"},{"key":"2025121514141398000_8.10.e020242.5","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.genhosppsych.2008.03.005","article-title":"Psychiatric emergencies in prehospital emergency medical systems: a prospective comparison of two urban settings","volume":"30","author":"Pajonk","year":"2008","journal-title":"Gen Hosp Psychiatry"},{"key":"2025121514141398000_8.10.e020242.6","doi-asserted-by":"publisher","DOI":"10.3109\/15622975.2015.1132007"},{"key":"2025121514141398000_8.10.e020242.7","doi-asserted-by":"crossref","DOI":"10.1186\/s12888-017-1373-4","article-title":"In-patient costs of agitation and containment in a mental health catchment area","volume":"17","author":"Serrano-Blanco","year":"2017","journal-title":"BMC Psychiatry"},{"key":"2025121514141398000_8.10.e020242.8","unstructured":"National Institute of Mental Health (NIMH). 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