{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T16:20:06Z","timestamp":1771950006246,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>HN0141 is a human cytomegalovirus (HCMV) DNA terminase complex inhibitor being developed for prophylaxis and\/or preemptive treatment of HCMV infection and diseases. This study evaluated the safety, tolerability, and pharmacokinetics (PK) of HN0141, following oral administration in healthy volunteers. The double\u2010blind, placebo\u2010controlled Phase 1 study comprised Part 1, an escalating, single\u2010dose study involving 50\u2010, 100\u2010, 200\u2010, 300\u2010, 400\u2010, and 525\u2010mg doses; and Part 2, a multiple\u2010dose study over 7 days involving 50\u2010, 100\u2010, 200\u2010, and 400\u2010mg twice\u2010daily doses. HN0141 was rapidly absorbed following oral doses, with median time to maximum concentration achieved within 1\u20102 hours across all doses. At doses ranging from 50 to 100\u00a0mg, the PK profile was reasonably linear, while at doses above 200\u00a0mg, the PK profile was more than proportional. The predicted therapeutic dose would be 50\u2010200\u00a0mg twice daily, which is at a reasonable linear PK range. All exposures tested (up to 525\u2010mg single dose and 400\u2010mg twice\u2010daily multiple doses) were within the no\u2010observed\u2010adverse\u2010effect level defined in animal toxicity studies. There was a mild accumulation on systemic exposure at steady state, which was achieved within 72 hours of multiple twice\u2010daily dosing. No serious or severe adverse events were reported. HN0141's PK profile favors the twice\u2010daily dosing, which gives a smaller concentration variation during the treatment, and thus could bring a better treatment effect with sufficient convenience. These Phase 1 data in safety and PK profile warrant further drug development in both preemptive and prophylactic treatment in patients with HCMV.<\/jats:p>","DOI":"10.1002\/cpdd.1542","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T09:41:51Z","timestamp":1747388511000},"page":"680-687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics and Safety Study of HN0141, a Novel Anti\u2010Human Cytomegalovirus Inhibitor, in Healthy Volunteers"],"prefix":"10.1002","volume":"14","author":[{"given":"George","family":"Hill","sequence":"first","affiliation":[{"name":"Clinical and Medical Science Department Phaeno Therapeutics Co. Ltd  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Gao","sequence":"additional","affiliation":[{"name":"Clinical and Medical Science Department Phaeno Therapeutics Co. Ltd  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingzhe","family":"Fan","sequence":"additional","affiliation":[{"name":"Clinical and Medical Science Department Phaeno Therapeutics Co. Ltd  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical and Medical Science Department Phaeno Therapeutics Co. Ltd  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Phase I Trial Center PKU Care Luzhong Hospital  Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoshan","family":"Zong","sequence":"additional","affiliation":[{"name":"Phase I Trial Center PKU Care Luzhong Hospital  Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinical and Medical Science Department Phaeno Therapeutics Co. Ltd  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghui","family":"Qin","sequence":"additional","affiliation":[{"name":"Clinical and Medical Science Department Phaeno Therapeutics Co. Ltd  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Hou","sequence":"additional","affiliation":[{"name":"Phase I Trial Center PKU Care Luzhong Hospital  Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/652438"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.DMIH2-0022-2015"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00697-14"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511545313"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.7402"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-679639"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/591532"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3062.2010.00504.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31829df29d"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12103"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.6.2502"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp090424"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2014.07.001"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2022.105328"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2024.286265"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706640"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70024-X"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000107"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01955-12"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.344"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1542","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T07:14:11Z","timestamp":1756797251000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":20,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/cpdd.1542"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1542","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,16]]},"assertion":[{"value":"2025-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}