{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:03:02Z","timestamp":1778270582489,"version":"3.51.4"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Early Intervention Psych"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Attenuated psychosis syndrome (APS), a condition for further study in the Diagnostic and Statistical Manual of Mental Disorders\u20105, comprises psychotic symptoms that are qualitatively similar to those observed in schizophrenia but are less severe. Patients with APS are at high risk of converting to first\u2010episode psychosis (FEP). As evidence for effective pharmacological interventions in APS is limited, novel treatments may provide symptomatic relief and delay\/prevent psychotic conversion. This trial aims to investigate the efficacy, safety, and tolerability of BI 409306, a potent and selective phosphodiesterase\u20109 inhibitor, versus placebo in APS. Novel biomarkers of psychosis are being investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this Phase II, multinational, double\u2010blind, parallel\u2010group trial, randomized (1:1) patients will receive BI 409306 50\u2009mg or placebo twice daily for 52\u2009weeks. Patients (<jats:italic>n<\/jats:italic>\u00a0=\u2009300) will be enrolled to determine time to remission of APS, time to FEP, change in everyday functional capacity (Schizophrenia Cognition Rating Scale), and change from baseline in Brief Assessment of Cognition composite score and Positive and Negative Syndrome Scale scores. Potential biomarkers of psychosis under investigation include functional measures of brain activity and automated speech analyses. Safety is being assessed throughout.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This trial will determine whether BI 409306 is superior to placebo in achieving sustainable remission of APS and improvements in cognition and functional capacity. These advances may provide evidence\u2010based treatment options for symptomatic relief in APS. Furthermore, the study will assess the effect of BI 409306 on psychotic conversion and explore the identification of patients at risk for conversion using novel biomarkers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eip.13083","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T09:40:00Z","timestamp":1608802800000},"page":"1315-1325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A randomized Phase <scp>II<\/scp> trial evaluating efficacy, safety, and tolerability of oral <scp>BI<\/scp> 409306 in attenuated psychosis syndrome: Design and rationale"],"prefix":"10.1111","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0173-8897","authenticated-orcid":false,"given":"Richard S. E.","family":"Keefe","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Duke University  Durham North Carolina USA"},{"name":"VeraSci  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott W.","family":"Woods","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyrone D.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University  New Haven Connecticut USA"},{"name":"Department of Psychology Yale University  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Ruhrmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel H.","family":"Mathalon","sequence":"additional","affiliation":[{"name":"Department of Psychology UCSF School of Medicine  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"McGuire","sequence":"additional","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Rosenbrock","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co KG  Biberach an der Riss Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Daniels","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals Inc.  Ridgefield Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Cotton","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals Inc.  Ridgefield Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dooti","family":"Roy","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals Inc.  Ridgefield Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephane","family":"Pollentier","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH  Ingelheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Sand","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals Inc.  Ridgefield Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10081191"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8934"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.10.010"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjschz.2015.30"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.09.025"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hup.2569"},{"key":"e_1_2_9_9_1","first-page":"S304","article-title":"Safety, tolerability, pharmacokinetics and pharmacodynamics of BI 409306 folm\u2010coated tablets given orally QD for 14\u2009days in patients with schizophrenia","volume":"41","author":"Brown D.","year":"2015","journal-title":"Schizophrenia Bulletin"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sby049"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20152"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2007.3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.05.023"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2016.15070890"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.170"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2015.13121686"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n0410"},{"issue":"2","key":"e_1_2_9_18_1","first-page":"84","article-title":"Rethinking psychosis: The disadvantages of a dichotomous classification now outweigh the advantages","volume":"6","author":"Craddock N.","year":"2007","journal-title":"World Psychiatry"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20526"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbx139"},{"key":"e_1_2_9_21_1","first-page":"S31","article-title":"BI 409306, a novel phosphodiesterase 9A inhibitor, part I: Potency, selectivity and in\u2010vitro functional characterization on synaptic plasticity","volume":"41","author":"Dorner\u2010Ciossek C.","year":"2015","journal-title":"Schizophrenia Bulletin"},{"key":"e_1_2_9_22_1","unstructured":"European Medicines Agency. (2012).Guideline on clinical investigation of medicinal products including depot preparations in the treatment of schizophrenia."},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.1472"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.269"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.114.157115"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.112.112300"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2008.07.008"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291713000354"},{"key":"e_1_2_9_29_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. (1996).ICH harmonised tripartite guideline: guideline for good clinical practice E6(1)."},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/13.2.261"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2014.06.009"},{"key":"e_1_2_9_32_1","first-page":"1S","article-title":"Impaired synaptic plasticity, synapti over\u2010pruning, inflammation, and stress: A pathogenic model of the transition to psychosis in clinical high risk youth","volume":"75","author":"Mathalon D. H.","year":"2014","journal-title":"Biological Psychiatry"},{"key":"e_1_2_9_33_1","volume-title":"The psychosis\u2010risk syndrome: Handbook for diagnosis and follow\u2010up","author":"McGlashan T. H.","year":"2010"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2006.163.5.790"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2016.2902"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.11.047"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-016-0764-8"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a007040"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(02)00440-1"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13060"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.06.496"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2018.01.003"},{"key":"e_1_2_9_43_1","unstructured":"National Collaborating Centre for Mental Health. (2014).Psychosis and schizophrenia in adults: The National Institute for Health and Care Excellence (NICE) guideline on treatment and management."},{"key":"e_1_2_9_44_1","unstructured":"National Institute for Health and Care Excellence (NICE). (2013).Psychosis and schizophrenia in children and young people: Recognition and management."},{"key":"e_1_2_9_45_1","unstructured":"National Institute for Health and Care Excellence (NICE). (2014).Psychosis and schizophrenia in adults: Prevention and management."},{"key":"e_1_2_9_46_1","unstructured":"Orygen: The National Centre of Excellence in Youth Mental Health. (2016).Australian clinical guidelines for early psychosis."},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbu099"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.206"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.3561"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1061"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2015.01.013"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2015.01.010"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16549"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.05.034"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1086\/BBLv219n2p81"},{"issue":"2","key":"e_1_2_9_56_1","first-page":"104","article-title":"Schizophrenia causes significant burden to patients' and caregivers' lives","volume":"28","author":"Szkultecka\u2010Debek M.","year":"2016","journal-title":"Psychiatria Danubina"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.04.022"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2009.07.023"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sby018.1039"},{"key":"e_1_2_9_60_1","unstructured":"World Medical Association. (2013).Declaration of Helsinki\u2014Ethical principles for medical research involving human subjects."},{"issue":"4","key":"e_1_2_9_61_1","first-page":"324","article-title":"Phase I studies evaluating the safety, tolerability, and pharmacokinetics of multiple\u2010rising doses of BI 409306 in young and elderly healthy volunteers","volume":"2","author":"Wunderlich G.","year":"2015","journal-title":"Journal of Prevention of Alzheimer's Disease"},{"issue":"19","key":"e_1_2_9_62_1","first-page":"30566","article-title":"Dynamic prediction of transition to psychosis using joint modelling","volume":"0920","author":"Yuen H. P.","year":"2019","journal-title":"Schizophrenia Research"}],"container-title":["Early Intervention in Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eip.13083","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/eip.13083","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eip.13083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T16:53:36Z","timestamp":1693328016000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eip.13083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,22]]},"references-count":61,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1111\/eip.13083"],"URL":"https:\/\/doi.org\/10.1111\/eip.13083","archive":["Portico"],"relation":{},"ISSN":["1751-7885","1751-7893"],"issn-type":[{"value":"1751-7885","type":"print"},{"value":"1751-7893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,22]]},"assertion":[{"value":"2019-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}