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CFTR modulators may improve outcomes in patients with COPD, although recent data regarding the magnitude of benefit have been inconclusive, and effects on mucociliary clearance are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We conducted a phase 2, randomized, double-blind, placebo-controlled trial to determine safety and tolerability and explore the potential mechanism of ivacaftor for the treatment of patients with COPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We randomized 40 patients with moderate to severe COPD and symptoms of chronic bronchitis to ivacaftor (n\u2009=\u200930) or placebo (n\u2009=\u200910) 150 mg twice daily for 12 weeks. Primary endpoints included evaluation of the safety of ivacaftor and pharmacokinetics. Secondary endpoints included measures of CFTR activity and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Ivacaftor was safe and tolerable, with similar rates of adverse events between groups. The most common adverse events were diarrhea in the ivacaftor group and acute COPD exacerbation in the placebo group. Pharmacokinetic analysis showed the mean area under the curve over 12 hours to be 72% of the previously reported value in cystic fibrosis. Treatment with ivacaftor did not improve sweat chloride, whole-lung mucociliary clearance, lung function, or respiratory symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ivacaftor was safe and well tolerated but did not improve measures of CFTR activity or mucus clearance. As serum concentrations achieved were lower than observed in cystic fibrosis at the same dose, and modulation of wild-type CFTR differs from G551D, further dose determination studies are needed to better understand the treatment efficacy of CFTR potentiators in COPD.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 03085485).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202407-1302oc","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T16:24:07Z","timestamp":1727195047000},"page":"823-831","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":9,"title":["Ivacaftor for Chronic Obstructive Pulmonary Disease: Results from a Phase 2, Randomized Controlled Trial"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6924-4335","authenticated-orcid":false,"given":"Kadambari","family":"Vijaykumar","sequence":"first","affiliation":[{"name":"Department of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George M.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Guimbellot","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward P.","family":"Acosta","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, and"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep G.","family":"Bhambhavni","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"White","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harrison","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Vamsee","family":"Raju","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence W.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Necole","family":"Harris","sequence":"additional","affiliation":[{"name":"Lung Health Center, Division of Pulmonary, Allergy and Critical Care Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Hathorne","sequence":"additional","affiliation":[{"name":"Gregory Fleming 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