Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial
Kentaro Machida,1,* Tomotaka Kawayama,2,* Masaharu Kinoshita,3,* Masakazu Ichinose,4 Tohru Tsuda,5 Shohei Takata,6 Hiroshi Koto,7 Makoto Yoshida,8 Yoshinori Ashihara,9 Masaru Kawashima,10 Hideaki Suna,10 Hiromasa Inoue1 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Science...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2019-09-01
|
Series: | International Journal of COPD |
Subjects: | |
Online Access: | https://www.dovepress.com/imidafenacin-an-orally-active-muscarinic-receptor-antagonist-improves--peer-reviewed-article-COPD |
id |
doaj-136fd10856154dfe8bb1075132b8f902 |
---|---|
record_format |
Article |
spelling |
doaj-136fd10856154dfe8bb1075132b8f9022020-11-25T00:48:35ZengDove Medical PressInternational Journal of COPD1178-20052019-09-01Volume 142175218448682Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II TrialMachida KKawayama TKinoshita MIchinose MTsuda TTakata SKoto HYoshida MAshihara YKawashima MSuna HInoue HKentaro Machida,1,* Tomotaka Kawayama,2,* Masaharu Kinoshita,3,* Masakazu Ichinose,4 Tohru Tsuda,5 Shohei Takata,6 Hiroshi Koto,7 Makoto Yoshida,8 Yoshinori Ashihara,9 Masaru Kawashima,10 Hideaki Suna,10 Hiromasa Inoue1 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan; 2Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan; 3Nagata Hospital, Yanagawa 832-0059, Japan; 4Department of Respiratory Medicine, Tohoku University, Graduate School of Medicine, Sendai 980-8574, Japan; 5Kirigaoka Tsuda Hospital, Kitakyushu 802-0052 Japan; 6Division of Respiratory Medicine, National Hospital Organization Fukuoka-Higashi Medical Center, Koga 811-3195, Japan; 7Division of Respiratory Medicine, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka 815-8588, Japan; 8Division of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka 811-1394, Japan; 9Division of Respiratory Medicine, Oita Nakamura Hospital, Oita 870-0022, Japan; 10ONO Pharmaceutical Co. Ltd., Osaka 541-8564, Japan*These authors contributed equally to this workCorrespondence: Hiromasa InoueDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, JapanTel +81 99 275 6481Fax +81 99 275 6482Email inoue-pulm@umin.netBackground: Although long-acting muscarinic receptor antagonists are central to the management of chronic obstructive pulmonary disease (COPD), inhaled medicines may have technical difficulty in some patients and adherence barriers.Methods: A multicenter, randomized, double-blind, placebo-controlled 3×3 crossover Phase II trial was performed to evaluate the efficacy and safety of oral administration of the antimuscarinic agent imidafenacin in patients with COPD. Twenty-seven male COPD patients with % forced expiratory volume in 1 s (FEV1) ≥30% and <80% predicted were randomized to single oral dose of imidafenacin 0.1 mg, imidafenacin 0.2 mg, or placebo.Results: Maximum change in FEV1 with both doses of imidafenacin significantly improved from baseline to 24 hrs after administration when compared with a placebo. Area under the curve in FEV1 during 24 hrs after administration with 0.2 mg, but not 0.1 mg dose, was significantly improved when compared with a placebo, and the improvement was significantly based on dose-dependent manners. Plasma imidafenacin level was positively correlated with change in FEV1. All subjects with both doses of imidafenacin completed without moderate nor severe adverse events.Conclusion: A single oral dose of imidafenacin 0.1 mg or imidafenacin 0.2 mg may contribute to the improvement of pulmonary function with excellent safety and tolerability in patients with COPD.Trial registration: JapicCTI-121760 (Japan Pharmaceutical Information Center – Clinical Trials Information [JapicCTI]; http://www.clinicaltrials.jp/user/cteSearch_e.jsp).Keywords: anti-cholinergic, bronchodilator, imidafenacin, lung function, COPDhttps://www.dovepress.com/imidafenacin-an-orally-active-muscarinic-receptor-antagonist-improves--peer-reviewed-article-COPDanti-cholinergicbronchodilatorimidafenacinlung functionCOPD |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Machida K Kawayama T Kinoshita M Ichinose M Tsuda T Takata S Koto H Yoshida M Ashihara Y Kawashima M Suna H Inoue H |
spellingShingle |
Machida K Kawayama T Kinoshita M Ichinose M Tsuda T Takata S Koto H Yoshida M Ashihara Y Kawashima M Suna H Inoue H Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial International Journal of COPD anti-cholinergic bronchodilator imidafenacin lung function COPD |
author_facet |
Machida K Kawayama T Kinoshita M Ichinose M Tsuda T Takata S Koto H Yoshida M Ashihara Y Kawashima M Suna H Inoue H |
author_sort |
Machida K |
title |
Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial |
title_short |
Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial |
title_full |
Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial |
title_fullStr |
Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial |
title_full_unstemmed |
Imidafenacin, An Orally Active Muscarinic Receptor Antagonist, Improves Pulmonary Function In Patients With Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled 3×3 Crossover Phase II Trial |
title_sort |
imidafenacin, an orally active muscarinic receptor antagonist, improves pulmonary function in patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled 3×3 crossover phase ii trial |
publisher |
Dove Medical Press |
series |
International Journal of COPD |
issn |
1178-2005 |
publishDate |
2019-09-01 |
description |
Kentaro Machida,1,* Tomotaka Kawayama,2,* Masaharu Kinoshita,3,* Masakazu Ichinose,4 Tohru Tsuda,5 Shohei Takata,6 Hiroshi Koto,7 Makoto Yoshida,8 Yoshinori Ashihara,9 Masaru Kawashima,10 Hideaki Suna,10 Hiromasa Inoue1 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan; 2Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan; 3Nagata Hospital, Yanagawa 832-0059, Japan; 4Department of Respiratory Medicine, Tohoku University, Graduate School of Medicine, Sendai 980-8574, Japan; 5Kirigaoka Tsuda Hospital, Kitakyushu 802-0052 Japan; 6Division of Respiratory Medicine, National Hospital Organization Fukuoka-Higashi Medical Center, Koga 811-3195, Japan; 7Division of Respiratory Medicine, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka 815-8588, Japan; 8Division of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka 811-1394, Japan; 9Division of Respiratory Medicine, Oita Nakamura Hospital, Oita 870-0022, Japan; 10ONO Pharmaceutical Co. Ltd., Osaka 541-8564, Japan*These authors contributed equally to this workCorrespondence: Hiromasa InoueDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, JapanTel +81 99 275 6481Fax +81 99 275 6482Email inoue-pulm@umin.netBackground: Although long-acting muscarinic receptor antagonists are central to the management of chronic obstructive pulmonary disease (COPD), inhaled medicines may have technical difficulty in some patients and adherence barriers.Methods: A multicenter, randomized, double-blind, placebo-controlled 3×3 crossover Phase II trial was performed to evaluate the efficacy and safety of oral administration of the antimuscarinic agent imidafenacin in patients with COPD. Twenty-seven male COPD patients with % forced expiratory volume in 1 s (FEV1) ≥30% and <80% predicted were randomized to single oral dose of imidafenacin 0.1 mg, imidafenacin 0.2 mg, or placebo.Results: Maximum change in FEV1 with both doses of imidafenacin significantly improved from baseline to 24 hrs after administration when compared with a placebo. Area under the curve in FEV1 during 24 hrs after administration with 0.2 mg, but not 0.1 mg dose, was significantly improved when compared with a placebo, and the improvement was significantly based on dose-dependent manners. Plasma imidafenacin level was positively correlated with change in FEV1. All subjects with both doses of imidafenacin completed without moderate nor severe adverse events.Conclusion: A single oral dose of imidafenacin 0.1 mg or imidafenacin 0.2 mg may contribute to the improvement of pulmonary function with excellent safety and tolerability in patients with COPD.Trial registration: JapicCTI-121760 (Japan Pharmaceutical Information Center – Clinical Trials Information [JapicCTI]; http://www.clinicaltrials.jp/user/cteSearch_e.jsp).Keywords: anti-cholinergic, bronchodilator, imidafenacin, lung function, COPD |
topic |
anti-cholinergic bronchodilator imidafenacin lung function COPD |
url |
https://www.dovepress.com/imidafenacin-an-orally-active-muscarinic-receptor-antagonist-improves--peer-reviewed-article-COPD |
work_keys_str_mv |
AT machidak imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT kawayamat imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT kinoshitam imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT ichinosem imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT tsudat imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT takatas imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT kotoh imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT yoshidam imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT ashiharay imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT kawashimam imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT sunah imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial AT inoueh imidafenacinanorallyactivemuscarinicreceptorantagonistimprovespulmonaryfunctioninpatientswithchronicobstructivepulmonarydiseaseamulticenterrandomizeddoubleblindplacebocontrolled3times3crossoverphaseiitrial |
_version_ |
1725255505248518144 |