{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:06:21Z","timestamp":1791266781362,"version":"4.1.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV 002384"],"award-info":[{"award-number":["INV 002384"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007729","name":"Ministerie van Buitenlandse Zaken","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007843","name":"Direktoratet for Utviklingssamarbeid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2023,3]]},"DOI":"10.1007\/s40262-023-01216-8","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T12:07:17Z","timestamp":1676030837000},"page":"481-491","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Determination of the Optimal Single Dose Treatment for Acoziborole, a Novel Drug for the Treatment of Human African Trypanosomiasis: First-in-Human Study"],"prefix":"10.1007","volume":"62","clinical-trial-number":[{"clinical-trial-number":"nct01533961","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1247-8653","authenticated-orcid":false,"given":"Antoine","family":"Tarral","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Hovsepian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Duvauchelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Donazzolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Latreille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Felices","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Gualano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Delhomme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Valverde Mordt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severine","family":"Blesson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Voiriot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Strub-Wourgaft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"1216_CR1","first-page":"i","volume":"984","author":"WHO","year":"2013","unstructured":"WHO. Control and surveillance of human African trypanosomiasis: report of a WHO expert committee. WHO Tech Rep Ser. 2013;984:i\u2013x (1\u2013237).","journal-title":"WHO Tech Rep Ser."},{"key":"1216_CR2","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/S0140-6736(09)60829-1","volume":"375","author":"R Brun","year":"2010","unstructured":"Brun R, Blum J, Chappuis F, Burri C. Human African trypanosomiasis. Lancet. 2010;375:148\u201359.","journal-title":"Lancet"},{"key":"1216_CR3","unstructured":"World Health Organization. WHO outlines criteria to assess elimination of sleeping sickness [Internet]. 2018. https:\/\/www.who.int\/neglected_diseases\/news\/criteria-eliminate-sleeping-sickness\/en\/. Accessed 16 Jul 2020."},{"issue":"1","key":"1216_CR4","doi-asserted-by":"publisher","first-page":"e0010047","DOI":"10.1371\/journal.pntd.0010047","volume":"16","author":"JR Franco","year":"2022","unstructured":"Franco JR, Cecchi G, Paone M, Diarra A, Grout L, et al. The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020. PLOS Negl Trop Dis. 2022;16(1):e0010047. https:\/\/doi.org\/10.1371\/journal.pntd.0010047.","journal-title":"PLOS Negl Trop Dis"},{"key":"1216_CR5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008261","volume":"14","author":"JR Franco","year":"2020","unstructured":"Franco JR, Cecchi G, Priotto G, et al. Monitoring the elimination of human African trypanosomiasis at continental and country level: Update to 2018. PLoS Negl Trop Dis. 2020;14: e0008261.","journal-title":"PLoS Negl Trop Dis"},{"key":"1216_CR6","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S0140-6736(09)61117-X","volume":"374","author":"G Priotto","year":"2009","unstructured":"Priotto G, Kasparian S, Mutombo W, Ngouama D, Ghorashian S, Arnold U, et al. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, Phase III, non-inferiority trial. Lancet (London, England). 2009;374:56\u201364.","journal-title":"Lancet (London, England)."},{"key":"1216_CR7","doi-asserted-by":"publisher","first-page":"e1920","DOI":"10.1371\/journal.pntd.0001920","volume":"6","author":"C Schmid","year":"2012","unstructured":"Schmid C, Kuemmerle A, Blum J, Ghabri S, Kande V, Mutombo W, et al. In-hospital safety in field conditions of nifurtimox eflornithine combination therapy (NECT) for T. b. gambiense sleeping sickness. PLoS Negl Trop Dis. 2012;6:e1920.","journal-title":"PLoS Negl Trop Dis"},{"key":"1216_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000923","volume":"4","author":"E Torreele","year":"2010","unstructured":"Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazu\u00e9 G, et al. Fexinidazole\u2014a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl Trop Dis. 2010;4: e923.","journal-title":"PLoS Negl Trop Dis"},{"key":"1216_CR9","doi-asserted-by":"publisher","first-page":"5602","DOI":"10.1128\/AAC.00246-11","volume":"55","author":"M Kaiser","year":"2011","unstructured":"Kaiser M, Bray MA, Cal M, Bourdin Trunz B, Torreele E, Brun R. Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness. Antimicrob Agents Chemother. 2011;55:5602\u20138.","journal-title":"Antimicrob Agents Chemother"},{"key":"1216_CR10","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1093\/mutage\/ges015","volume":"27","author":"D Tweats","year":"2012","unstructured":"Tweats D, Bourdin Trunz B, Torreele E. Genotoxicity profile of fexinidazole\u2013a drug candidate in clinical development for human African trypanomiasis (sleeping sickness). Mutagenesis. 2012;27:523\u201332.","journal-title":"Mutagenesis"},{"key":"1216_CR11","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s40262-014-0136-3","volume":"53","author":"A Tarral","year":"2014","unstructured":"Tarral A, Blesson S, Mordt OV, Torreele E, Sassella D, Bray MA, et al. Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: first-in-human studies. Clin Pharmacokinet. 2014;53:565\u201380.","journal-title":"Clin Pharmacokinet"},{"key":"1216_CR12","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/S0140-6736(17)32758-7","volume":"391","author":"VKBK Mesu","year":"2018","unstructured":"Mesu VKBK, Kalonji WM, Bardonneau C, Mordt OV, Blesson S, Simon F, et al. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet. 2018;391:144\u201354.","journal-title":"Lancet"},{"key":"1216_CR13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001151","volume":"5","author":"RT Jacobs","year":"2011","unstructured":"Jacobs RT, Nare B, Wring SA, Orr MD, Chen D, Sligar JM, et al. SCYX-7158, an orally-active benzoxaborole for the treatment of stage 2 human African trypanosomiasis. PLoS Negl Trop Dis. 2011;5: e1151.","journal-title":"PLoS Negl Trop Dis"},{"key":"1216_CR14","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1017\/S003118201300098X","volume":"141","author":"S Wring","year":"2014","unstructured":"Wring S, Gaukel E, Nare B, Jacobs R, Beaudet B, Bowling T, et al. Pharmacokinetics and pharmacodynamics utilizing unbound target tissue exposure as part of a disposition-based rationale for lead optimization of benzoxaboroles in the treatment of Stage 2 Human African Trypanosomiasis. Parasitology. 2014;141:104\u201318.","journal-title":"Parasitology"},{"key":"1216_CR15","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.4155\/fmc.11.80","volume":"3","author":"RT Jacobs","year":"2011","unstructured":"Jacobs RT, Plattner JJ, Nare B, Wring SA, Chen D, Freund Y, et al. Benzoxaboroles: a new class of potential drugs for human African trypanosomiasis. Future Med Chem. 2011;3:1259\u201378.","journal-title":"Future Med Chem"},{"key":"1216_CR16","unstructured":"ICH HARMONISED TRIPARTITE GUIDELINE FOR GOOD CLINICAL PRACTICE E6 (R1). https:\/\/www.ema.europa.eu\/en\/ich-e6-r2-good-clinical-practice#document-history-revision-1-section.\n Accessed 16 Jul 2020."},{"key":"1216_CR17","doi-asserted-by":"crossref","unstructured":"Trainor GL. Chapter 31. Plasma protein binding and the free drug principle: recent developments and applications. Annu Rep Med Chem. 2007;42:489\u2013502. https:\/\/doi.org\/10.1016\/S0065-7743(07)42031-0.","DOI":"10.1016\/S0065-7743(07)42031-0"}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-023-01216-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-023-01216-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-023-01216-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T01:44:42Z","timestamp":1679881482000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-023-01216-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["1216"],"URL":"https:\/\/doi.org\/10.1007\/s40262-023-01216-8","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,10]]},"assertion":[{"value":"19 January 2023","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 February 2023","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"See title page.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"VG and MF declare employment by PhinC Development, a CRO sub-contracted for this project. PV is CMO and President of Cardiabase, which provided central ECG services during the study. AT, SD, OV, SB, and NSW declare employment by study sponsor Drugs for Neglected Diseases <i>initiative.<\/i> YD declares employment by Eurofins Optimed. TD declares employment by SGS Aster at the time of the study. No other potential conflicts of interest were declared.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The data underlying the results of this study are available upon request because they contain potentially sensitive information. Interested researchers may contact the Drugs for Neglected Diseases initiative (DNDi), commissioner of this study, for data access requests via email at CTdata@dndi.org. Researchers may also request data by completing the form available at\n                      \n                      . In this, they confirm that they will share data and results with DNDi and will publish any results open access.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"This study was conducted in accordance with the Declaration of Helsinki, French Huriet law (No. 2004-806), and Good Clinical Practice guidelines. The protocol and amendments were approved by the Committee of Protection of Persons (Paris, France) and by the national competent authority (Agence Nationale de S\u00e9curit\u00e9 du M\u00e9dicament).","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from all participants","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"AT, OV, SD SB, NSW, TD, LH, and VG conceived and designed the experiments; LH, TD, ML, and YD performed the clinical studies; VG, MF and PV analysed the data and performed the statistical and pharmacokinetic analyses.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}}]}}