{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:12:22Z","timestamp":1790921542722,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Dipeptidyl peptidase\u20101 (DPP\u20101) inhibitors have been studied for the treatment of neutrophil\u2010mediated inflammatory diseases including bronchiectasis, bronchial asthma and cystic fibrosis. This study evaluated the pharmacokinetics, pharmacodynamics, safety and tolerability of DPP\u20101 inhibitor HSK31858 in healthy Chinese volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Volunteers in Part A randomly received single doses of HSK31858 (15, 40, 60 and 80\u2009mg) or placebo in fasted states. The 40\u2010mg cohort also received HSK31858 40\u2009mg or placebo in fed states. In Part B, volunteers randomly received HSK31858 10, 20 and 40\u2009mg or placebo once daily for 28\u2009days in fasted states. The primary endpoints were safety and tolerability of HSK31858.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 38 volunteers in Part A and 36 in Part B, HSK31858 was well tolerated; no deaths, serious adverse events, or discontinuations due to adverse events occurred. The median <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub> was 0.75 to 1.0\u00a0h and the mean terminal <jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub> was 16.5 to 21.0\u00a0h in the fasted state with single doses of HSK31858. Both <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u2010<jats:italic>t<\/jats:italic><\/jats:sub> exhibited a dose\u2010dependent rise. Food had no effect on AUC. Multiple doses of HSK31858 demonstrated a similar pharmacokinetics profile, with about 2\u2010fold accumulation in AUC. HSK31858 dose\u2010dependently inhibited neutrophil count\u2010normalized neutrophil elastase (NE<jats:sub>norm<\/jats:sub>) activity. The maximal percentage decrease in NE<jats:sub>norm<\/jats:sub> activity relative to baseline during 28\u2009days of HSK31858 treatments was 13.6% and 76.4% with HSK31858 10 and 40\u2009mg once\u2010daily, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HSK31858 was safe and well tolerated. The pharmacokinetics and pharmacodynamics profile of HSK31858 supports further clinical development for the treatment of neutrophil\u2010mediated inflammatory diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>NCT05663593.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bcp.70027","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T03:39:50Z","timestamp":1743565190000},"page":"2262-2272","source":"Crossref","is-referenced-by-count":9,"title":["Safety, tolerability, pharmacokinetics and pharmacodynamics of HSK31858, a novel oral dipeptidyl peptidase\u20101 inhibitor, in healthy volunteers: An integrated phase 1, randomized, double\u2010blind, placebo\u2010controlled, single\u2010 and multiple\u2010ascending dose study"],"prefix":"10.1002","volume":"91","author":[{"given":"Yuhao","family":"Wang","sequence":"first","affiliation":[{"name":"Haisco Pharmaceutical Group Co. Ltd  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Yu","sequence":"additional","affiliation":[{"name":"Haisco Pharmaceutical Group Co. Ltd  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyue","family":"Hu","sequence":"additional","affiliation":[{"name":"Haisco Pharmaceutical Group Co. Ltd  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Phase I Trial Center Peking University Care, Luzhong Hospital  Zibo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixia","family":"Chen","sequence":"additional","affiliation":[{"name":"Haisco Pharmaceutical Group Co. Ltd  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanmo","family":"Liu","sequence":"additional","affiliation":[{"name":"Haisco Pharmaceutical Group Co. Ltd  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3817-2716","authenticated-orcid":false,"given":"Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"Haisco Pharmaceutical Group Co. Ltd  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-9386","authenticated-orcid":false,"given":"Jie","family":"Hou","sequence":"additional","affiliation":[{"name":"Phase I Trial Center Peking University Care, Luzhong Hospital  Zibo China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra012519"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0015\u20102023"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20102600(20)30504\u2010x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02990\u20102020"},{"key":"e_1_2_11_6_1","first-page":"6","article-title":"Inflammation: a two\u2010edged sword\u2014the model of bronchiectasis","volume":"147","author":"Cole PJ","year":"1986","journal-title":"Eur J Respir Dis Suppl"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(18)31767\u20107"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD000996.pub3"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.03157\u20102020"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00148\u20102015"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.04.022"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201605\u20101027OC"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2012.12.009"},{"issue":"60","key":"e_1_2_11_14_1","article-title":"Safety and tolerability of the NE inhibitor BAY 85\u20108501 in patients with non\u2010CF bronchiectasis","volume":"48","author":"Watz H","year":"2016","journal-title":"Eur Respir J"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1053"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00151\u20102024"},{"key":"e_1_2_11_17_1","unstructured":"NewswireP.Insmed announces positive topline results from landmark Aspen study of Brensocatib in patients with bronchiectasis. May 28 2024.https:\/\/investor.insmed.com\/2024-05-28-Insmed-Announces-Positive-Topline-Results-from-Landmark-ASPEN-Study-of-Brensocatib-in-Patients-with-Bronchiectasis"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13398"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011\u2010023\u201001774\u20104"},{"key":"e_1_2_11_20_1","unstructured":"National Medical products Administration.Good clinical practice.2020."},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021713"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1239151"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1094"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\u2010conference.2022.205.1_MeetingAbstracts.A4777"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/70472"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523\u20101747.2001.01244.x"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T07:15:58Z","timestamp":1753773358000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,2]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/bcp.70027"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70027","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,2]]}}}