A randomised, single blind, cross-over study to compare a fixed dose combination of fluticasone propionate / formoterol fumarate (fluticasone /formoterol breath actuated inhaler (BAI)) with a fixed dose combination of indacaterol maleate / glycopyrronium bromide (Ultibro® Breezhaler) in subjects with fixed airflow obstruction and elevated eosinophils.

INTERVENTION: Trade Name: flutiform® 125 microgram / 5 microgram per actuation pressurised inhalation, suspension Product Name: Fluticasone/formoterol BAI 125/5 µg Product Code: K‐haler Pharmaceutical Form: Pressurised inhalation, suspension INN or Proposed INN: fluticasone propionate CAS Number: 80474‐14‐2 Other descriptive name: FLUTICASONE PROPIONATE Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 125‐ INN or Proposed INN: / formoterol fumarate dihydrate Other descriptive name: / FORMOTEROL FUMARATE DIHYDRATE Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 5‐ Trade Name: Ultibro® Breezhaler 85 micrograms/43 micrograms, inhalation powder hard capsules Pharmaceutical Form: Inhalation powder, hard capsule INN or Proposed INN: indacaterol maleate CAS Number: 753498‐25‐8 Other descriptive name: INDACATEROL MALEATE Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 143‐ INN or Proposed INN: / GLYCOPYRRONIUM BROMIDE CAS Number: / 596‐51‐0 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 63‐ CONDITION: Fixed airflow obstruction with elevated eosinophils ; MedDRA version: 18.1 Level: LLT Classification code 10077006 Term: Asthma‐COPD overlap syndrome System Organ Class: 100000004855 Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] PRIMARY OUTCOME: Main Objective: To compare the efficacy of fluticasone /formoterol BAI 125/5 microgram (2 puffs b.i.d.) versus Ultibro Breezhaler 85/43 microgram (1 puff o.d.) in terms of the percentage of eosinophils in induced sputum at Week 6 of each treatment. Primary end point(s): Change from baseline in eosinophil count (percentage of total cell count) in induced sputum at Week 6 Secondary Objective: Key Secondary Objective:; To compare the efficacy of fluticasone /formoterol BAI 125/5 microgram (2 puffs b.i.d.) versus Ultibro Breezhaler 85/43 microgram (1 puff o.d.) in terms of the serum concentration of SPD at Week 6 of each treatment. ; ; Only the Key Secondary Objective is listed here.; Please refer to section 7.3 of the protocol (Final Version 2.0, 26 Nov 2015) for the full list of Secondary Objectives. Timepoint(s) of evaluation of this end point: Evaluation after study end. No interim analysis planned. Please refer to section 14.21 of the protocol. SECONDARY OUTCOME: Secondary end point(s): Key Secondary efficacy endpoint:; Change from baseline in serum concentration of the SPD at Week 6; ; Other secondary efficacy endpoints: ; ; ‐ Change from baseline in percentage of blood eosinophils at Week 6; ‐ Change from baseline in serum concentration of CCL‐18 at Week 6; ‐ Change from baseline in concentration of nitric oxide in exhaled air (bronchial FENO) at Week 3 and Week 6 (exhaled at 50 mL/s); ‐ Change from baseline in alveolar nitric oxide (in a subgroup of subjects) at Week 3 and Week 6 measured at 50, 100 and 150mL/sec; ‐ Change from baseline in EXACT‐respiratory symptoms (EXACT‐RS) dyspnoea score averaged over 6‐week treatment period; ‐ Changes from baseline in EXACT total score averaged over the 6‐week treatment period; ‐ Changes from baseline in mean rescue medication use measured morning and evening over 6 weeks of treatment; ‐ Change from baseline in ACQ at Week 6; ‐ Change from baseline in CAT at Week 6; ‐ Changes from baseline in pre‐dose FEV1 & FVC at Week 6; ‐ Changes from baseline in mean peak expiratory flow rate (PEFR) measured morning and evening (prior to taking study medication) over 6 weeks of treatment using electronic subject diary; ‐ Change from baseline in oscillometric parameters (R5, R20, R5 ‐ R20, AX, RF, X5) at Week 6 of each treatment (in a subgroup); ‐ Change from baseline in percentage of neutrophils, macrophages and lymphocytes in induced sputum at Week 6 of each treatment. Timepoint(s) of evaluation of this end point: Evaluation after study end. No interim analysis planned. Please refer to section 14.21 of the protocol. INCLUSION CRITERIA: 1. Male or female subjects aged equal or major than to 40 years at Screening visit. 2. Adequate contraception: ‐ Female subjects of child bearing potential (less than 1 year post‐menopausal) must have a negative urine pregnancy test prior to first dose of study medication, be non‐lactating, and willing to use adequate and highly effective methods of birth control throughout the study such as sterilisation, implants, injectables, combined oral contraceptives, some intra‐uterine devices, sexual abstinence, where this is line with the preferred and usual lifestyle of the subject or vasectomised partner. Note: Periodic abstinence (calendar, ovulation, symptothermal, post‐ovulation methods), declaration of abstinence for duration of study, and withdrawal are not acceptable methods of contraception). ‐ Male subjects with a partner of child‐bearing potential must be willing to use adequate and highly effective methods of birth control throughout the study (