{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:00:27Z","timestamp":1792166427037,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the <jats:italic>Wolbachia<\/jats:italic> bacterial endosymbiont present in the causative nematode parasites. This phase 1, first\u2010in\u2010human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double\u2010blind, placebo\u2010controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600\u00a0mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400\u00a0mg of AWZ1066S progressed unremarkably. After single 700\u2010mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis.<\/jats:p>","DOI":"10.1002\/cpdd.1441","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T05:34:57Z","timestamp":1719293697000},"page":"1071-1081","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Phase 1, Randomized, Double\u2010Blind, Placebo\u2010Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti\u2010<i>Wolbachia<\/i> Candidate Macrofilaricide"],"prefix":"10.1002","volume":"13","author":[{"given":"Graham","family":"Devereux","sequence":"first","affiliation":[{"name":"Clinical Sciences Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Bula","sequence":"additional","affiliation":[{"name":"Clinical Research Facility Royal Liverpool University Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Tripp","sequence":"additional","affiliation":[{"name":"Clinical Research Facility Royal Liverpool University Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Clinical Research Facility Royal Liverpool University Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Eraut","sequence":"additional","affiliation":[{"name":"Fortrea Clinical Research Unit Ltd  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Salman","family":"Alam","sequence":"additional","affiliation":[{"name":"Labcorp Early Development Laboratories Limited  Huntingdon Cambridgeshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Moriyama","sequence":"additional","affiliation":[{"name":"Eisai Co., Ltd. Global Drug Safety  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raku","family":"Shinkyo","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics Eisai Inc. Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Walker","sequence":"additional","affiliation":[{"name":"Clinical Research Facility Royal Liverpool University Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duolao","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Sciences Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Gusovsky","sequence":"additional","affiliation":[{"name":"Global Public Health, Eisai Inc. Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"van der Velde","sequence":"additional","affiliation":[{"name":"Global Public Health, Eisai Inc. Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Turner","sequence":"additional","affiliation":[{"name":"Centres for Drugs &amp; Diagnostics and Neglected Tropical Disease Department of Tropical Disease Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqian David","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"O'Neill","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Centres for Drugs &amp; Diagnostics and Neglected Tropical Disease Department of Tropical Disease Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Ward","sequence":"additional","affiliation":[{"name":"Centres for Drugs &amp; Diagnostics and Neglected Tropical Disease Department of Tropical Disease Biology Liverpool School of Tropical Medicine  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60586-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30286-2"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI140853"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001366"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.85.8.897"},{"key":"e_1_2_8_7_1","first-page":"115","article-title":"Global data on blindness","volume":"73","author":"Thylefors B","year":"1995","journal-title":"Bull World Health Organ"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/383326"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2120003119"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2021.06.004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04581-5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(03)00026-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66591-9"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020092"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/586753"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-007-0062-1"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2009.09-0155"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000660"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aao1551"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816585116"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.2c00167"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1346068"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00322-5"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2007.01949.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex440"},{"key":"e_1_2_8_26_1","first-page":"19","article-title":"Principles and applications of liquid chromatography\u2010mass spectrometry in clinical biochemistry","volume":"30","author":"Pitt JJ","year":"2009","journal-title":"Clin Biochem Rev"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2011.11.038"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20081"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1211"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-023-07414-w"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jech-2016-208730"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2383"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005280851"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(98)70014-4"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710845114"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1441","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T01:55:11Z","timestamp":1725242111000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,24]]},"references-count":34,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/cpdd.1441"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1441","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,24]]},"assertion":[{"value":"2024-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}