Gefapixant in two randomised dose-escalation studies in chronic cough
Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach. Two randomis...
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| Veröffentlicht in: | The European respiratory journal 2020-03, Vol.55 (3), p.1901615 |
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| container_title | The European respiratory journal |
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| creator | Smith, Jaclyn A Kitt, Michael M Butera, Peter Smith, Steven A Li, Yuping Xu, Zhi Jin Holt, Kimberley Sen, Shilpi Sher, Mandel R Ford, Anthony P |
| description | Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach.
Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50-200 mg, study 2: 7.5-50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.
In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p |
| doi_str_mv | 10.1183/13993003.01615-2019 |
| format | Article |
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Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50-200 mg, study 2: 7.5-50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.
In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg.
P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.</description><identifier>ISSN: 0903-1936</identifier><identifier>EISSN: 1399-3003</identifier><identifier>DOI: 10.1183/13993003.01615-2019</identifier><identifier>PMID: 31949115</identifier><language>eng</language><publisher>England</publisher><subject>Chronic Disease ; Cough - drug therapy ; Double-Blind Method ; Humans ; Pyrimidines ; Sulfonamides ; Treatment Outcome</subject><ispartof>The European respiratory journal, 2020-03, Vol.55 (3), p.1901615</ispartof><rights>Copyright ©ERS 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c350t-448666f4f22bb4116666eb5d372beebbe7782023433feea7255b8cd062f532353</citedby><cites>FETCH-LOGICAL-c350t-448666f4f22bb4116666eb5d372beebbe7782023433feea7255b8cd062f532353</cites><orcidid>0000-0001-8837-4928</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31949115$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Smith, Jaclyn A</creatorcontrib><creatorcontrib>Kitt, Michael M</creatorcontrib><creatorcontrib>Butera, Peter</creatorcontrib><creatorcontrib>Smith, Steven A</creatorcontrib><creatorcontrib>Li, Yuping</creatorcontrib><creatorcontrib>Xu, Zhi Jin</creatorcontrib><creatorcontrib>Holt, Kimberley</creatorcontrib><creatorcontrib>Sen, Shilpi</creatorcontrib><creatorcontrib>Sher, Mandel R</creatorcontrib><creatorcontrib>Ford, Anthony P</creatorcontrib><title>Gefapixant in two randomised dose-escalation studies in chronic cough</title><title>The European respiratory journal</title><addtitle>Eur Respir J</addtitle><description>Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach.
Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50-200 mg, study 2: 7.5-50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.
In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg.
P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.</description><subject>Chronic Disease</subject><subject>Cough - drug therapy</subject><subject>Double-Blind Method</subject><subject>Humans</subject><subject>Pyrimidines</subject><subject>Sulfonamides</subject><subject>Treatment Outcome</subject><issn>0903-1936</issn><issn>1399-3003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMFOwzAQRC0EoqXwBUgoRy4pXm_sJEdUtQWpEhc4W7azoUFpXOJEwN-T0JbTakczs6vH2C3wOUCGD4B5jpzjnIMCGQsO-Rmbjmo8yudsynOOMeSoJuwqhA8-GBOESzZByJMcQE7Zck2l2Vffpumiqom6Lx-1pin8rgpURIUPFFNwpjZd5ZsodH1RURidbtv6pnKR8_379ppdlKYOdHOcM_a2Wr4unuLNy_p58biJHUrexUmSKaXKpBTC2gRgWBRZWWAqLJG1lKaZ4AITxJLIpEJKm7mCK1FKFChxxu4PvfvWf_YUOj386aiuTUO-D3qIghJibJgxPFhd60NoqdT7ttqZ9kcD1yM_feKn__jpkd-Qujse6O2Oiv_MCRj-Aoktad4</recordid><startdate>202003</startdate><enddate>202003</enddate><creator>Smith, Jaclyn A</creator><creator>Kitt, Michael M</creator><creator>Butera, Peter</creator><creator>Smith, Steven A</creator><creator>Li, Yuping</creator><creator>Xu, Zhi Jin</creator><creator>Holt, Kimberley</creator><creator>Sen, Shilpi</creator><creator>Sher, Mandel R</creator><creator>Ford, Anthony P</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8837-4928</orcidid></search><sort><creationdate>202003</creationdate><title>Gefapixant in two randomised dose-escalation studies in chronic cough</title><author>Smith, Jaclyn A ; Kitt, Michael M ; Butera, Peter ; Smith, Steven A ; Li, Yuping ; Xu, Zhi Jin ; Holt, Kimberley ; Sen, Shilpi ; Sher, Mandel R ; Ford, Anthony P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c350t-448666f4f22bb4116666eb5d372beebbe7782023433feea7255b8cd062f532353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Chronic Disease</topic><topic>Cough - drug therapy</topic><topic>Double-Blind Method</topic><topic>Humans</topic><topic>Pyrimidines</topic><topic>Sulfonamides</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smith, Jaclyn A</creatorcontrib><creatorcontrib>Kitt, Michael M</creatorcontrib><creatorcontrib>Butera, Peter</creatorcontrib><creatorcontrib>Smith, Steven A</creatorcontrib><creatorcontrib>Li, Yuping</creatorcontrib><creatorcontrib>Xu, Zhi Jin</creatorcontrib><creatorcontrib>Holt, Kimberley</creatorcontrib><creatorcontrib>Sen, Shilpi</creatorcontrib><creatorcontrib>Sher, Mandel R</creatorcontrib><creatorcontrib>Ford, Anthony P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The European respiratory journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smith, Jaclyn A</au><au>Kitt, Michael M</au><au>Butera, Peter</au><au>Smith, Steven A</au><au>Li, Yuping</au><au>Xu, Zhi Jin</au><au>Holt, Kimberley</au><au>Sen, Shilpi</au><au>Sher, Mandel R</au><au>Ford, Anthony P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gefapixant in two randomised dose-escalation studies in chronic cough</atitle><jtitle>The European respiratory journal</jtitle><addtitle>Eur Respir J</addtitle><date>2020-03</date><risdate>2020</risdate><volume>55</volume><issue>3</issue><spage>1901615</spage><pages>1901615-</pages><issn>0903-1936</issn><eissn>1399-3003</eissn><abstract>Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach.
Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50-200 mg, study 2: 7.5-50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.
In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg.
P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.</abstract><cop>England</cop><pmid>31949115</pmid><doi>10.1183/13993003.01615-2019</doi><orcidid>https://orcid.org/0000-0001-8837-4928</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Chronic Disease Cough - drug therapy Double-Blind Method Humans Pyrimidines Sulfonamides Treatment Outcome |
| title | Gefapixant in two randomised dose-escalation studies in chronic cough |
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