A Comparison Study Between the Fixed Dose Triple Combination of Fluticasone Furoate/ Umeclidinium/ Vilanterol Trifenatate (FF/UMEC/VI) With Budesonide/Formoterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Summary

This is a phase IIIa, randomised, double-blind, double-dummy, parallel group multicenter study evaluating once daily FF/UMEC/VI (100 microgram \[mcg\]/62.5 mcg/25 mcg) inhalation powder versus twice daily budesonide/formoterol (400 mcg/12 mcg). The primary purpose of this study is to demonstrate improvements in lung function and health status for subjects treated with FF/UMEC/VI compared with budesonide/formoterol for 24 weeks. Once-daily 'closed' triple therapy of a Inhaled Corticosteroid/ Long-acting Muscarinic Receptor Antagonists/ Long Acting Beta-Agonist (ICS/LAMA/LABA) combination FF/UMEC/VI (100 mcg/62.5 mcg/25 mcg) in a single device is being developed with the aim of providing a new treatment option for the management of advanced (GOLD Group D) COPD which will reduce the exacerbation frequency, allow for a reduced burden of polypharmacy, convenience, and increase the potential for improvement in lung function, Health Related Quality of Life (HRQoL) and symptom control over established dual/monotherapies. Subjects meeting all inclusion/exclusion criteria and who have successfully completed all protocol procedures at the Screening Visit will enter the two-week run-in period. Following the run-in period, eligible subjects will be randomised (1:1) to one of the following double-blind treatment groups: FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg via the ELLIPTA™ dry powder inhaler (DPI) once daily in the morning and placebo via reservoir inhaler twice daily OR Budesonide/formoterol 400 mcg/12 mcg via reservoir inhaler twice daily and placebo via the ELLIPTA DPI once daily in the morning. The target enrollment is 1800 randomised subjects at approximately 200 study centers globally. The total duration of subject participation will be approximately 27 weeks, consisting of a 2-week run-in period, 24-week treatment period and a 1-week follow-up period. Subjects will run-in on their existing COPD medications for 2 weeks and in addition will be provided with short acting albuterol/salbutamol to be used on an as-needed basis (rescue medication) throughout the study. Subjects will discontinue all existing COPD medications during the randomised treatment period but may continue their study supplied rescue albuterol/salbutamol. A sub-set of approximately 400 subjects will remain on blinded study treatment for up to a total of 52 weeks to provide additional long term safety data. ELLIPTA and NUBULES are a trade marks of the GlaxoSmithKline Group of Companies. Other company or product names mentioned herein may be the property of their respective owners

Timeline

Start

2015-01-23

Primary completion

2016-04-01

Completion

2016-04-07

Publications

• Lipson DA, Birk R, Brealey N, Zhu CQ. 24-Hour Serial Spirometric Assessment of Once-Daily Fluticasone Furoate/Umeclidinium/Vilanterol Versus Twice-Daily Budesonide/Formoterol in Patients with COPD: Analysis of the FULFIL Study. Adv Ther. 2020 Dec;37(12):4894-4909. doi: 10.1007/s12325-020-01496-7. Epub 2020 Oct 3.
• Schroeder M, Benjamin N, Atienza L, Biswas C, Martin A, Whalen JD, Izquierdo Alonso JL, Riesco Miranda JA, Soler-Cataluna JJ, Huerta A, Ismaila AS. Cost-Effectiveness Analysis of a Once-Daily Single-Inhaler Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease (COPD) Using the FULFIL Trial: A Spanish Perspective. Int J Chron Obstruct Pulmon Dis. 2020 Jul 10;15:1621-1632. doi: 10.2147/COPD.S240556. eCollection 2020.
• Mehta R, Farrell C, Hayes S, Birk R, Okour M, Lipson DA. Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease. Clin Pharmacokinet. 2020 Jan;59(1):67-79. doi: 10.1007/s40262-019-00794-w.
• Naya I, Compton C, Ismaila AS, Birk R, Brealey N, Tabberer M, Zhu CQ, Lipson DA, Criner G. Preventing clinically important deterioration with single-inhaler triple therapy in COPD. ERJ Open Res. 2018 Oct 3;4(4):00047-2018. doi: 10.1183/23120541.00047-2018. eCollection 2018 Oct.
• Tabberer M, Lomas DA, Birk R, Brealey N, Zhu CQ, Pascoe S, Locantore N, Lipson DA. Once-Daily Triple Therapy in Patients with COPD: Patient-Reported Symptoms and Quality of Life. Adv Ther. 2018 Jan;35(1):56-71. doi: 10.1007/s12325-017-0650-4. Epub 2018 Jan 8.
• Ismaila AS, Birk R, Shah D, Zhang S, Brealey N, Risebrough NA, Tabberer M, Zhu CQ, Lipson DA. Once-Daily Triple Therapy in Patients with Advanced COPD: Healthcare Resource Utilization Data and Associated Costs from the FULFIL Trial. Adv Ther. 2017 Sep;34(9):2163-2172. doi: 10.1007/s12325-017-0604-x. Epub 2017 Sep 5.
• Lipson DA, Barnacle H, Birk R, Brealey N, Locantore N, Lomas DA, Ludwig-Sengpiel A, Mohindra R, Tabberer M, Zhu CQ, Pascoe SJ. FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Aug 15;196(4):438-446. doi: 10.1164/rccm.201703-0449OC.

Drugs

Indications