Clinical trial NCT02345161
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Triple Therapy Formoterol Respiratory COPD Budesonide Vilanterol Fluticasone Furoate Umeclidinium Lung Function
Sponsor: GlaxoSmithKline
Start date: 2015-01-23; Completion date: 2016-04-07
Enrollment: 1811 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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

Detailed description:

Arms: arm 1: Each subject will inhale once from their ELLIPTA DPI and once from the reservoir inhaler in the morning and once from the reservoir inhaler in the evening, for 24 weeks (or 52 weeks for subjects participating in the extension part of the study). Subjects will receive FF/UMEC/VI (100mcg/62.5mcg/25mcg) via the ELLIPTA DPI and placebo via reservoir inhaler. arm 2: Each subject will inhale once from their ELLIPTA DPI and once from the reservoir inhaler in the morning and once from the reservoir inhaler in the evening, for 24 weeks (or 52 weeks for subjects participating in the extension part of the study). Subjects will receive Budesonide/formoterol (400mcg/12mcg) via reservoir inhaler and placebo via the ELLIPTA DPI.
Interventions: intervention 1: Triple FF/UMEC/VI intervention 2: Placebo to match FF/UMEC/VI intervention 3: Budesonide/Formoterol intervention 4: Placebo to match Budesonide/Formoterol combination intervention 5: Albuterol/salbutamol
Intervention descriptions: intervention 1: The combination will be provided as inhalation via an ELLIPTA DPI having 30 doses (2 strips with 30 blisters per strip). It will have 100 mcg of FF (blended with lactose) per blister, 62.5 mcg of UMEC (blended with lactose and magnesium stearate) per blister and 25 mcg of VI (blended with lactose) per blister. intervention 2: The placebo (Lactose) will be provided as inhalation via an ELLIPTA DPI having 30 doses (2 strips with 30 blisters per strip). intervention 3: The combination (400 mcg Budesonide/12 mcg Formoterol) will be provided as inhalation via TURBOHALER with 60 doses. intervention 4: The placebo (Lactose) will be provided as inhalation via TURBOHALER with 60 doses. intervention 5: Albuterol/salbutamol will be available as an inhalation via metered-dose inhaler (MDI) with a spacer and will be issued for reversibility testing at Visit 1 Albuterol/salbutamol MDI or NEBULES™ for as needed (prn) use throughout the study will be provided starting at Visit 1.

Protocol documents: