{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:47:06Z","timestamp":1782107226595,"version":"3.54.5"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osivelotor (GBT021601) is an orally bioavailable, small molecule hemoglobin polymerization inhibitor in clinical development for the treatment of sickle cell disease (SCD). In this Phase 1 study, the disposition of osivelotor was assessed using accelerator mass spectrometry (AMS) after a single oral 200\u2010mg dose containing a microtracer amount of [\n                    <jats:sup>14<\/jats:sup>\n                    C]\u2010labeled osivelotor (~74\u2009kBq [~2\u2009\n                    <jats:italic>\u03bc<\/jats:italic>\n                    Ci]) was received by nine healthy volunteers. Due to a long half\u2010life (27\u201330\u2009days), continuous and non\u2010continuous sample collection was needed over a nearly 7\u2010month study. The results indicate an average 87.6% (47.2% in urine; 40.4% in feces) recovery of the dose in excreta. Comparison of osivelotor and total radioactivity (TRA) systemic concentration versus time profiles in whole blood and plasma suggests the absence of a long\u2010lived metabolite. Osivelotor was the main circulating drug\u2010related material in plasma (68.1% of [\n                    <jats:sup>14<\/jats:sup>\n                    C]). Also observed in plasma was a glucuronide metabolite (19.7% of [\n                    <jats:sup>14<\/jats:sup>\n                    C]). In whole blood, the effect compartment, only osivelotor (98.3% of [\n                    <jats:sup>14<\/jats:sup>\n                    C]) was present and no metabolites were observed. The single oral 200\u2010mg dose of osivelotor was well tolerated. The results of this unique study design provide insights into the absorption, metabolism, and excretion (ADME) of osivelotor and support its continued development for SCD.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    NCT05718687\n                  <\/jats:p>","DOI":"10.1111\/cts.70601","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T13:43:16Z","timestamp":1779716596000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase 1 Microtracer Study Evaluating the Mass Balance, Excretion, and Pharmacokinetics of Osivelotor in Healthy Participants"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0055-4403","authenticated-orcid":false,"given":"Eric I.","family":"Zimmerman","sequence":"first","affiliation":[{"name":"Pfizer Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8429-0724","authenticated-orcid":false,"given":"Ernesto","family":"Callegari","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3106-7809","authenticated-orcid":false,"given":"Raman","family":"Sharma","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeyemi","family":"Adenola","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7874-4913","authenticated-orcid":false,"given":"Jessica","family":"Volpe","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Seetharaman","sequence":"additional","affiliation":[{"name":"Pfizer Inc  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4729-6199","authenticated-orcid":false,"given":"Chenghong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pfizer Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8213-3127","authenticated-orcid":false,"given":"Kenneth","family":"Duchin","sequence":"additional","affiliation":[{"name":"Pfizer Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0129-1682","authenticated-orcid":false,"given":"Gregory S.","family":"Walker","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199709113371107"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-10-880575"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2017.1.435"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2025.2489123"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18771"},{"key":"e_1_2_11_7_1","first-page":"120","article-title":"Safety, Pharmacokinetics, and Pharmacodynamics of Osivelotor for Sickle Cell Disease: First\u2010In\u2010Human Studies in Healthy Participants and Patients","author":"Lisbon E. A.","year":"2025","journal-title":"Clinical Pharmacology and Therapeutics"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.5c00076"},{"key":"e_1_2_11_9_1","volume-title":"Radiological Protection in Biomedical Research","author":"ICRP","year":"1992"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.616"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac5015035"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1890"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmd.2025.100067"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.3473"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-014-2468-y"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2010.06.012"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-017-0509-1"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.039339"},{"key":"e_1_2_11_19_1","unstructured":"Global Blood Therapeutics ClinicalTrials.gov.\u201cA Study of the Absorption Metabolism and Excretion of GBT440 in Healthy Male Subjects (NCT02497924) \u201d(2017)."}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70601","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70601","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70601","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:52:38Z","timestamp":1782103958000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/cts.70601"],"URL":"https:\/\/doi.org\/10.1111\/cts.70601","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"assertion":[{"value":"2026-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70601"}}