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

Inclusion criteria

Patients had to meet all of the following inclusion criteria to be eligible for enrolment into the study:

• Male and female adults aged ≥ 40 years with written informed consent obtained prior to any study-related procedure;
• Patients with a diagnosis of COPD (according to GOLD 2015 strategic document, updated January 2015) at least 12 months before the screening visit;
• A smoking history of at least 10 pack years [pack years = (number of cigarettes per day x number of years)/20]. Current and ex-smokers were eligible; Note: Smoking cessation therapy had to be completed 6 months prior to screening visit.
• A post-bronchodilator FEV1 450 ms for males or QTcF > 470 ms for females at screening and at randomisation visits were not eligible.
• Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that in the opinion of the Investigator would prevent use of anticholinergic agents;
• History of hypersensitivity to M3 antagonists, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial;
• Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study treatment according to Investigator's judgement;
• Patients with serum potassium levels < 3.5 mEq/L (or 3.5 mmol/L) at screening;
• Unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; uncontrolled gastrointestinal disease (e.g. active peptic ulcer); neurological disease; uncontrolled haematological disease; uncontrolled autoimmune disorders, or other which may impact the feasibility of the results of the study according to Investigator's judgement;
• History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit;
• Participation in another clinical trial where investigation drug was received less than 8 weeks prior to screening visit;
• Patients treated with Traditional Chinese Medicines used for respiratory diseases.

All exclusion criteria except for criterion #4 were checked at screening (V1, Week -2).

The following exclusion criteria were to be re-checked at the randomisation visit (V2, Week 0): #1,

#4, #5, #6, #7, #10, #11, #12, #17, and #20. For patients in South Korea (only), the following were added to the South Korea-specific protocol (version 3.0):

• For exclusion criterion #14, it was additionally specified that patients with a history of lactose intolerance were to be excluded;
• For exclusion criterion #17, it was additionally specified that patients with a known history of hypersensitivity to sympathomimetic amine were to be excluded;
• An additional exclusion criterion (#21) was specified for patients with a known history of hypertrophic cardiomyopathy.