Active Controlled Trial of CHF5993 Pressurized Metered-dose Inhaler ( pMDI) vs Symbicort®Turbuhaler® in Patients With Chronic Obstructive Pulmonary Disease ( COPD) (TRIVERSYTI)

This was a phase III, 24-week, randomised, double-blind, double-dummy, Multinational (China, South Korea, Taiwan), Multicentre, 2-arm parallel-group, active-controlled study in patients with COPD.

The study was designed to demonstrate the superiority of CHF 5993 pMDI over budesonide/formoterol in terms of pulmonary function (change from baseline in pre-dose morning FEV1 and 2-hour post-dose morning FEV1 at Week 24), both in the overall study population and in the Chinese population. The study lasted approximately 27 weeks for each patient, and a total of 7 clinic visits (Visit \[V\] 0 to V6) were performed during the study, plus a follow-up phone call.

A pre-screening visit (Visit \[V\] 0) was planned to occur no more than 7 days before a screening visit (V1, Week -2), followed by a 2-week open-label run-in period on Symbicort® Turbuhaler® (budesonide/formoterol fumarate \[FF\] 160/4.5 μg per inhalation), 2 inhalations twice daily (BID) (total daily dose: 640/18 μg budesonide/FF). The 2-week run-in period was deemed sufficient in order to 'standardise' the target population on the same treatment (Symbicort® Turbuhaler® \[budesonide/FF 160/4.5 μg per inhalation\]) prior to randomisation to study treatments, without leading to a deterioration in the disease.

At the randomisation visit (V2, Week 0), patients were randomised in a 1:1 ratio to one of the following two treatments for 24 weeks:

* CHF 5993 pMDI, 2 inhalations BID (total daily dose: 400/24/50 μg beclometasone dipropionate \[BDP\]/FF/glycopyrronium bromide \[GB\]); * Symbicort® Turbuhaler®, 2 inhalations BID (total daily dose: 640/18 μg budesonide/FF).

The length of the treatment period (24 weeks) was considered as adequate to evaluate the long-term efficacy and safety of CHF 5993 pMDI 100/6/12.5 μg versus (vs) budesonide/formoterol in terms of lung function.

Salbutamol was purchased locally by the vendor and used as rescue medication on an as-needed basis during both the run-in and treatment periods.

Four subsequent visits were performed after 4 weeks (V3), 12 weeks (V4), 18 weeks (V5), and 24 weeks (V6) of treatment. A time window of ±3 days was allowed for the visit dates from V2 to V6. An early termination (ET) visit was to be performed in the event of premature study discontinuation, during which all efforts were made to perform the assessments that should have been done at Week 24 (V6). A safety follow-up phone call was scheduled with the patient 7-10 days after last study treatment intake or ET visit in order to check the status of any unresolved adverse events (AEs) at the last visit.