Lung function improvements following inhaled indacaterol/glycopyrronium/mometasone furoate are independent of dosing time in asthma patients: a randomised trial

Jutta Beier; Henrik Watz; Zuzana Diamant; Jens M Hohlfeld; Dave Singh; Pascale Pinot; Ieuan Jones; Hanns-Christian Tillmann

doi:10.1183/23120541.00425-2020

Lung function improvements following inhaled indacaterol/glycopyrronium/mometasone furoate are independent of dosing time in asthma patients: a randomised trial

ERJ Open Res. 2021 Apr 19;7(2):00425-2020. doi: 10.1183/23120541.00425-2020. eCollection 2021 Apr.

Authors

Jutta Beier¹, Henrik Watz², Zuzana Diamant^{3

4

5}, Jens M Hohlfeld^{6

7

8}, Dave Singh⁹, Pascale Pinot¹⁰, Ieuan Jones¹¹, Hanns-Christian Tillmann¹⁰

Affiliations

¹ Insaf Respiratory Research Institute, Wiesbaden, Germany.
² Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research (DZL), Grosshansdorf, Germany.
³ Dept of Respiratory Medicine and Allergology, Institute for Clinical Science, Skåne University Hospital, Lund, Sweden.
⁴ Dept of Microbiology, Immunology and Transplantation, KU Leuven, Catholic University of Leuven, Leuven, Belgium.
⁵ Dept of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre and QPS-NL, Groningen, The Netherlands.
⁶ German Center for Lung Research (BREATH), Hannover, Germany.
⁷ Dept of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
⁸ Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
⁹ University of Manchester, Medicines Evaluation Unit, Manchester University NHS Foundation Trust, Manchester, UK.
¹⁰ Novartis Institutes for Biomedical Research, Basel, Switzerland.
¹¹ Novartis Pharma AG, Basel, Switzerland.

Abstract

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 (LABA)), 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 morning and evening versus placebo in patients with mild-moderate asthma. The primary end-point was weighted mean forced expiratory volume in 1 s (FEV₁) over 24 h following 14 days of IND/GLY/MF dosed a.m. and p.m. versus placebo. Secondary end-points 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 (area under the curve from 0 to 24 h) by 610 mL (90% CI 538-681 mL) and 615 mL (90% CI 544-687 mL), respectively, versus placebo. Mean PEF over 14 days increased by 70.7 L·min^-1 (90% CI 60.5-80.9 L·min^-1) following a.m. dosing, and by 59.7 L·min^-1 (90% CI 49.5-69.9 L·min^-1) following p.m. 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 a.m. or p.m. dosing, in patients with mild-moderate asthma.