TY - JOUR T1 - Lung function improvements following inhaled indacaterol/glycopyrronium/mometasone furoate are independent of dosing time in asthma patients: a randomised trial JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00425-2020 SP - 00425-2020 AU - Jutta Beier AU - Henrik Watz AU - Zuzana Diamant AU - Jens M. Hohlfeld AU - Dave Singh AU - Pascale Pinot AU - Ieuan Jones AU - Hanns-Christian Tillmann Y1 - 2020/01/01 UR - http://openres.ersjournals.com/content/early/2020/11/19/23120541.00425-2020.abstract N2 - Once-daily asthma treatment should prevent night-time deterioration, irrespective of the time of dosing. IND/GLY/MF, a fixed-dose combination of inhaled indacaterol acetate (IND, long-acting β2-agonist), glycopyrronium bromide (GLY, long-acting muscarinic antagonist), and mometasone furoate (MF, inhaled corticosteroid [ICS]) delivered by Breezhaler®, is indicated in adult asthma patients inadequately controlled on LABA/ICS.A randomised, double-blind, placebo-controlled, three-period, crossover, phase II study was performed to investigate the bronchodilator effect of IND/GLY/MF (150/50/80 μg) dosed am and pm versus placebo in patients with mild-moderate asthma. The primary endpoint was weighted mean forced expiratory volume in 1 s (FEV1) over 24 h following 14 days of IND/GLY/MF dosed am and pm versus placebo. Secondary endpoints included the effect of dosing time on peak expiratory flow (PEF) and safety/tolerability.Of 37 randomised patients (age 18–72 years, 21 male, 16 female) 34 completed all three treatment periods. At screening, median (range) pre-bronchodilator FEV1 was 75.8% (60–96). Patients were using stable low- (83.8%) or medium-dose (16.2%) ICS. Morning and evening dosing of IND/GLY/MF improved FEV1 (AUC0–24h) by 610 mL (90% CI: 538, 681) and 615 mL (90% CI: 544, 687), respectively, versus placebo. Mean PEF over 14 days increased by 70.7 L·min−1 (90% CI: 60.5, 80.9) following am dosing, and by 59.7 L·min−1 (90% CI: 49.5, 69.9) following pm dosing of IND/GLY/MF versus placebo. IND/GLY/MF demonstrated a safety profile comparable with placebo.Once-daily inhaled IND/GLY/MF was well tolerated and provided sustained lung function improvements over 24 h, irrespective of am or pm dosing, in patients with mild-moderate asthma.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Beier reports personal fees from Novartis, during the conduct of the study; personal fees from AstraZeneca, personal fees from Berlich Chemie/Menarini, personal fees from Pohl Boskamp, outside the submitted work.Conflict of interest: Dr. Watz reports grants, personal fees and non-financial support from Novartis, during the conduct of the study; grants, personal fees and non-financial support from AZ, grants, personal fees and non-financial support from BerlinChemie/Menarini, grants, personal fees and non-financial support from GSK, grants, personal fees and non-financial support from Chiesi, grants, personal fees and non-financial support from Bayer, grants, personal fees and non-financial support from Takeda, outside the submitted work.Conflict of interest: Dr. Diamant reports grants from Novartis, during the conduct of the study; personal fees from Acucort, personal fees from Astrazeneca, personal fees from ALK, personal fees from Aquilon, personal fees from Boehringer Ingelheim, personal fees from CSL, personal fees from HAL Allergy, personal fees from MSD, personal fees from Sanofi Genzyme, outside the submitted work.Conflict of interest: J.M. Hohlfeld reports grants paid to his institution from Novartis during the conduct of the study; and consultancy fees from Boehringer Ingelheim, grants paid to his institution from AstraZeneca AB, Novartis, Janssen Pharmaceutica NV, ALK, Boehringer Ingelheim, LETI, GlaxoSmithKline and grants from Sanofi-Aventis, consultancy fees from Merck & Co, Inc., lecture fees from Novartis, grants paid to his institution from Astellas Pharma and Allergopharma, and lectures fees from HAL, outside the submitted work.Conflict of interest: Dr. Singh reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from Cipla, personal fees from Genentech, personal fees from GlaxoSmithKline, personal fees from Glenmark, personal fees from Gossamerbio, personal fees from Menarini, personal fees from Mundipharma, personal fees from Novartis, personal fees from Peptinnovate, personal fees from Pfizer, personal fees from Pulmatrix, personal fees from Theravance, personal fees from Verona, outside the submitted work.Conflict of interest: Dr. Pinot is an employee of NovartisConflict of interest: Dr. Jones is an employee of NovartisConflict of interest: Dr. Tillmann is an employee of Novartis ER -