{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:39:07Z","timestamp":1790699947174,"version":"4.1.0"},"reference-count":30,"publisher":"European Respiratory Society (ERS)","issue":"6","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005612","name":"Shionogi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005612","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2021,10,5]]},"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The purinoceptor subtype P2X\n                      <jats:sub>3<\/jats:sub>\n                      has been shown to have significant involvement in the cough reflex; the heterotrimer version of the purinoceptor (P2X\n                      <jats:sub>2\/3<\/jats:sub>\n                      ) has been implicated in taste disturbance. The most advanced clinical candidate antagonist gefapixant has low selectivity among P2X\n                      <jats:sub>3<\/jats:sub>\n                      receptors and induced taste disturbance, whereas newly developed sivopixant has high selectivity towards P2X\n                      <jats:sub>3<\/jats:sub>\n                      <jats:italic>versus<\/jats:italic>\n                      P2X\n                      <jats:sub>2\/3<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a phase 2a, randomised, double-blind, placebo-controlled, crossover, multicentre study, adult patients with refractory or unexplained chronic cough received oral sivopixant 150\u2005mg or placebo once daily for 2\u2005weeks, followed by a 2\u20133-week washout period, and then crossed over to placebo or sivopixant for 2\u2005weeks. Efficacy and safety of sivopixant were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 31 randomised patients, 15 in the sivopixant-first group and 15 in the placebo-first group completed the study. After 2\u2005weeks of treatment, the placebo-adjusted ratios of the average hourly number of coughs to baseline during daytime (primary end-point) and over 24\u2005h (secondary end-point) were \u221231.6% (p=0.0546) and \u221230.9% (p=0.0386), respectively. Sivopixant also improved health-related quality of life. Treatment-related adverse events occurred in 12.9% and 3.2% of patients during sivopixant and placebo administration, respectively. Mild taste disturbance occurred in two patients (6.5%) during sivopixant administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sivopixant reduced objective cough frequency and improved health-related quality of life, with a low incidence of taste disturbance, among patients with refractory or unexplained chronic cough.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.00725-2021","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T12:03:15Z","timestamp":1634212995000},"page":"2100725","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["Randomised trial of the P2X\n                    <sub>3<\/sub>\n                    receptor antagonist sivopixant for refractory chronic cough"],"prefix":"10.1183","volume":"59","author":[{"given":"Akio","family":"Niimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpei","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Kamei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Shinkai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Ishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuaki","family":"Machida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"2024102102423217000_59.6.2100725.1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00218714"},{"key":"2024102102423217000_59.6.2100725.2","unstructured":"Alhajjaj MS , Bajaj P . Chronic cough. 2020. www.ncbi.nlm.nih.gov\/books\/NBK430791 Date last accessed: 22 February 2021."},{"key":"2024102102423217000_59.6.2100725.3","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-015-9701-2"},{"key":"2024102102423217000_59.6.2100725.4","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01136-2019"},{"key":"2024102102423217000_59.6.2100725.5","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejim.2020.03.018","article-title":"Chronic cough in adults","volume":"78","author":"Spanevello","year":"2020","journal-title":"Eur J Intern Med"},{"key":"2024102102423217000_59.6.2100725.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-010-9272-1"},{"key":"2024102102423217000_59.6.2100725.7","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-011-9271-6"},{"key":"2024102102423217000_59.6.2100725.8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fncel.2013.00267","article-title":"The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders","volume":"7","author":"Ford","year":"2013","journal-title":"Front Cell Neurosci"},{"key":"2024102102423217000_59.6.2100725.9","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S2213-2600(19)30471-0","article-title":"Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial","volume":"8","author":"Smith","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2024102102423217000_59.6.2100725.10","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01615-2019"},{"key":"2024102102423217000_59.6.2100725.11","unstructured":"Kai H , Horiguchi T , Kameyama T . Dioxotriazine derivatives as a new class of P2X3 receptor antagonists. Part 2: discovery of clinical candidate S-600918. 2020. https:\/\/plan.core-apps.com\/acs_sf20\/abstract\/589b55d9-2baf-4901-98fc-2271aa3b5fda Date last accessed: 22 October 2021."},{"key":"2024102102423217000_59.6.2100725.12","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.congress-2019.RCT452"},{"key":"2024102102423217000_59.6.2100725.13","first-page":"A7647","article-title":"Phase 2a randomised, double-blind, placebo-controlled, crossover study of a P2x3 receptor antagonist S-600918: effects on health-related quality of life in patients with refractory chronic cough","volume":"201","author":"Niimi","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"2024102102423217000_59.6.2100725.14","unstructured":"Niimi A , Ishihara H , Hida H . [Phase 2a randomised, double-blind, placebo-controlled study of a P2X3 receptor antagonist S-600918 in patients with refractory chronic cough: correlation between changes in cough frequency and Leicester Cough Questionnaire score]. Abstract presented at: Japanese Society of Allergology\/World Allergy Organisation Joint Congress 2020; 17 September\u201320 October 2020."},{"key":"2024102102423217000_59.6.2100725.15","unstructured":"Niimi A , Ishihara H , Hida H . [Phase 2a randomised, double-blind, placebo-controlled, crossover study of a P2X3 antagonist S-600918: effects on health-related quality of life in patients with refractory chronic cough]. Encore abstract presented at: 22nd Annual Meeting of the Japan Cough Society; 26\u201327 September 2020."},{"key":"2024102102423217000_59.6.2100725.16","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.58.4.339"},{"key":"2024102102423217000_59.6.2100725.17","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.alit.2016.02.014","article-title":"Gastroesophageal dysmotility is associated with the impairment of cough-specific quality of life in patients with cough variant asthma","volume":"65","author":"Kanemitsu","year":"2016","journal-title":"Allergol Int"},{"key":"2024102102423217000_59.6.2100725.18","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.jval.2016.03.1834","article-title":"Comparison of value set based on DCE and\/or TTO data: scoring for EQ-5D-5L health states in Japan","volume":"19","author":"Shiroiwa","year":"2016","journal-title":"Value Health"},{"key":"2024102102423217000_59.6.2100725.19","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-79842-2_16"},{"key":"2024102102423217000_59.6.2100725.20","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S2213-2600(20)30083-7","article-title":"Managing unexplained chronic cough in adults: what are the unmet needs?","volume":"8","author":"Irwin","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2024102102423217000_59.6.2100725.21","first-page":"315","article-title":"From the cover: drug-induced taste disorders in clinical practice and preclinical safety evaluation","volume":"156","author":"Wang","year":"2017","journal-title":"Toxicol Sci"},{"key":"2024102102423217000_59.6.2100725.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.wjorl.2018.02.005"},{"key":"2024102102423217000_59.6.2100725.23","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.281014"},{"key":"2024102102423217000_59.6.2100725.24","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.04240-2020"},{"key":"2024102102423217000_59.6.2100725.25","unstructured":"Merck & Co., Inc. Merck's gefapixant (45\u2005mg twice daily) significantly decreased cough frequency compared to placebo at week 12 and 24 in patients with refractory or unexplained chronic cough. Data from phase 3 COUGH-1 AND COUGH-2 trials presented at the virtual European Respiratory Society (ERS) International Congress 2020. 2020. www.merck.com\/news\/mercks-gefapixant-45-mg-twice-daily-significantly-decreased-cough-frequency-compared-to-placebo-at-week-12-and-24-in-patients-with-refractory-or-unexplained-chronic-cough Date last accessed: 28 May 2021."},{"key":"2024102102423217000_59.6.2100725.26","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.58.10.901"},{"key":"2024102102423217000_59.6.2100725.27","doi-asserted-by":"crossref","first-page":"101854","DOI":"10.1016\/j.pupt.2019.101854","article-title":"Interfering with airway nerves in cough associated with asthma","volume":"59","author":"Niimi","year":"2019","journal-title":"Pulm Pharmacol Ther"},{"key":"2024102102423217000_59.6.2100725.28","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.2147\/COPD.S240033","article-title":"Day and night control of COPD and role of pharmacotherapy: a review","volume":"15","author":"Braghiroli","year":"2020","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"2024102102423217000_59.6.2100725.29","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.jaip.2019.08.053","article-title":"Clinical characteristics of cough frequency patterns in patients with and without asthma","volume":"8","author":"Fukuhara","year":"2020","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2024102102423217000_59.6.2100725.30","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.resinv.2021.01.007","article-title":"The Japanese Respiratory Society guidelines for the management of cough and sputum (digest edition)","volume":"59","author":"Mukae","year":"2021","journal-title":"Respir Investig"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.00725-2021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:48:15Z","timestamp":1740358095000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.00725-2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,2]]},"published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1183\/13993003.00725-2021"],"URL":"https:\/\/doi.org\/10.1183\/13993003.00725-2021","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,14]]}}}