{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:36Z","timestamp":1787013936212,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015086","name":"AOP Orphan Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015086","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2019,5]]},"abstract":"Summary<\/jats:title>\n \n Anagrelide is an established treatment option for essential thrombocythaemia (\n ET<\/jats:styled-content>\n ). A prolonged release formulation was developed with the aim of reducing dosing frequency and improving tolerability, without diminishing efficacy. This multicentre, randomized, double blind, active\u2010controlled, non\u2010inferiority trial investigated the efficacy, safety and tolerability of anagrelide prolonged release (A\u2010\n PR<\/jats:styled-content>\n ) over a reference product in high\u2010risk\n ET<\/jats:styled-content>\n patients, either anagrelide\u2010na\u00efve or \u2010experienced. In a 6 to 12\u2010week titration period the individual dose for the consecutive 4\u2010week maintenance period was identified. The primary endpoint was the mean platelet count during the maintenance period (3 consecutive measurements, day 0, 14, 28). Of 112 included patients 106 were randomized. The mean screening platelet counts were 822\u00a0\u00d7\u00a010\n 9<\/jats:sup>\n \/l (95% confidence interval (\n CI<\/jats:styled-content>\n ) 707\u2013936\u00a0\u00d7\u00a010\n 9<\/jats:sup>\n \/l) and 797\u00a0\u00d7\u00a010\n 9<\/jats:sup>\n \/l (95%\n CI<\/jats:styled-content>\n 708\u2013883\u00a0\u00d7\u00a010\n 9<\/jats:sup>\n \/l) for A\u2010\n PR<\/jats:styled-content>\n and the reference product, respectively. Both treatments effectively reduced platelet counts, to mean 281\u00a0\u00d7\u00a010\n 9<\/jats:sup>\n \/l for A\u2010\n PR<\/jats:styled-content>\n (95%\n CI<\/jats:styled-content>\n 254\u2013311) and 305\u00a0\u00d7\u00a010\n 9<\/jats:sup>\n \/l (95%\n CI<\/jats:styled-content>\n 276\u2013337) for the reference product (\n P<\/jats:italic>\n \u00a0<\u00a00\u00b70001, for non\u2010inferiority). Safety and tolerability were comparable between both drugs. The novel prolonged\u2010release formulation was equally effective and well tolerated compared to the reference product. A\u2010\n PR<\/jats:styled-content>\n provides a more convenient dosing schedule and will offer an alternative to licensed immediate\u2010release anagrelide formulations.\n <\/jats:p>","DOI":"10.1111\/bjh.15824","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T08:45:13Z","timestamp":1553762713000},"page":"691-700","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A phase\n III<\/scp>\n randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia \u2013 the\n TEAM<\/scp>\n \u2010\n ET<\/scp>\n 2\u00b70 trial"],"prefix":"10.1111","volume":"185","author":[{"given":"Heinz","family":"Gisslinger","sequence":"first","affiliation":[{"name":"Department of Haematology and Blood Coagulation Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Buxhofer\u2010Ausch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Krankenhaus der Elisabethinen Linz Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri","family":"Hodisch","sequence":"additional","affiliation":[{"name":"AOP Orphan Pharmaceuticals AG Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atanas","family":"Radinoff","sequence":"additional","affiliation":[{"name":"Clinic of Oncology and Haematology Tokuda Hospital Sofia Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Karyagina","sequence":"additional","affiliation":[{"name":"City Hospital 15 St. Petersburg Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slawomira","family":"Kyrcz\u2010Krzemie\u0144","sequence":"additional","affiliation":[{"name":"Samodzielny Publiczny Szpital Kliniczny im Andrzeja Miel\u0119ckiego \u015al\u0105skiego Uniwersytetu Medycznego w Katowicach Katowice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kudrat","family":"Abdulkadyrov","sequence":"additional","affiliation":[{"name":"Russian Scientific\u2010Research Institute for Haematology and Transfusiology St. Petersburg Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolandas","family":"Gerbutavicius","sequence":"additional","affiliation":[{"name":"LSMU Hospital Kauno Clinics Haematology Clinic Kaunas Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anait","family":"Melikyan","sequence":"additional","affiliation":[{"name":"Haemotology Research Centre Moscow Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Burgstaller","sequence":"additional","affiliation":[{"name":"Abteilung f\u00fcr Innere Medizin IV Klinikum Wels\u2010Grieskirchen Wels Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Hus","sequence":"additional","affiliation":[{"name":"Klinika Hematoonkologii i Transplantacji Szpiku Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"K\u0142oczko","sequence":"additional","affiliation":[{"name":"Klinika Hematologii z Pododzia\u0142em Chor\u00f3b Naczy\u0144 Uniwersytecki Szpital Kliniczny w Bia\u0142ymstoku Bia\u0142ystok Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Yablokova","sequence":"additional","affiliation":[{"name":"Yaroslavl Regional Clinical Hospital Yaroslavl Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay","family":"Tzvetkov","sequence":"additional","affiliation":[{"name":"MHAT Dr. Georgi Stranski Clinic of Haematology Pleven Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Ca\u0142becka","sequence":"additional","affiliation":[{"name":"Oddzia\u0142 Hematologii Specjalistyczny Szpital Miejski im. M. Kopernika w Toruniu Torun Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Shneyder","sequence":"additional","affiliation":[{"name":"Leningrad Regional Clinical Hospital St. Petersburg Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Warzocha","sequence":"additional","affiliation":[{"name":"Instytut Hematologii i Transfuzjologii Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindaugas","family":"Jurgutis","sequence":"additional","affiliation":[{"name":"Klaipeda Seamen's Hospital Klaipeda Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Kaplanov","sequence":"additional","affiliation":[{"name":"Volgograd Regional Clinical Oncology Dispensary Volgograd Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5652-7977","authenticated-orcid":false,"given":"Bernd","family":"Jilma","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2286-1077","authenticated-orcid":false,"given":"Christian","family":"Schoergenhofer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Klade","sequence":"additional","affiliation":[{"name":"AOP Orphan Pharmaceuticals AG Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1055\/s-0038-1661206","article-title":"Inhibition of platelet production induced by an antiplatelet drug, anagrelide, in normal volunteers","volume":"52","author":"Abe Andes W.","year":"1984","journal-title":"Thrombosis and Haemostasis"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12959"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0b013e32834bb867"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.31.8436"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.64"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12759"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2012.18.7.527"},{"key":"e_1_2_8_9_1","unstructured":"CPMP. (1999)Note for Guidance on modified release products: oral and transdermal dosage forms Section\u00a0II (Pharmacokinetic and clinical evaluation). CPMP\/EWP\/280\/96 Corr *.The European Agency for the Evaluation of Medicinal Products London. Available at:https:\/\/www.ema.europa.eu\/documents\/scientific-guideline\/note-guidance-modified-release-oral-transdermal-dosage-forms-section-ii-pharmacokinetic-clinical_en.pdf(Accessed July 1 2017)."},{"key":"e_1_2_8_10_1","unstructured":"CPMP. (2002)Points to consider on multiplicity issues in clinical trials. CPMP\/EWP\/908\/99.The European Agency for the Evaluation of Medicinal Products London. Available at:https:\/\/www.ema.europa.eu\/documents\/scientific-guideline\/points-consider-multiplicity-issues-clinical-trials_en.pdf. (Accessed July 1 2017)."},{"key":"e_1_2_8_11_1","unstructured":"CPMP. (2003)Points to consider on the clinical requirements of modified release products submitted as a line extension of an existing marketing authorisation. CPMP\/EWP\/1875\/03\/Final.The European Agency for the Evaluation of Medicinal Products London. Available at:https:\/\/www.ema.europa.eu\/documents\/scientific-guideline\/points-consider-clinical-requirements-modified-release-products-submitted-line-extension-existing_en.pdf. (Accessed July 1 2017)."},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12850"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8510(90)90421-9"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(79)90145-2"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2004.10.002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-443770"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-014-1631-x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-014-2224-8"},{"key":"e_1_2_8_19_1","first-page":"1","article-title":"Adherence to cardiovascular medication: a review of systematic reviews","author":"Leslie K.H.","year":"2018","journal-title":"Journal of Public Health"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3111\/13696998.2015.1074584"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu046"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-013-1265-4"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.13346"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-942760"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2009.02.008"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.340"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-015-1186-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.17219\/acem\/68578"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-015-1218-2"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12554"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198805193182002"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20646"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404955"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2015.03.014"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2014.964853"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.15824","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.15824","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.15824","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.15824","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T08:38:59Z","timestamp":1694335139000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.15824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,28]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1111\/bjh.15824"],"URL":"https:\/\/doi.org\/10.1111\/bjh.15824","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,28]]},"assertion":[{"value":"2018-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}