TRIple in Asthma hiGh strenGth vErsus Ics/Laba hs and tiotRopium (TRIGGER)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the superiority of CHF 5993 200/6/12.5 µg pMDI (fixed combination of extrafine beclometasone dipropionate plus formoterol fumarate plus glycopyrronium bromide) versus CHF 1535 200/6 µg pMDI (fixed combination of extrafine beclometasone dipropionate plus formoterol fumarate) and to compare the effect of CHF 5993 200/6/12.5 µg pMDI vs CHF 5993 200/6/12.5 µg plus open-label Tiotropium 2.5µg, in terms of lung functions parameters and rate of exacerbations, as well as to assess its safety and some health economics outcomes.

Official Title
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A 52 WEEK, RANDOMIZED, DOUBLE BLIND, MULTINATIONAL, MULTICENTRE, ACTIVE CONTROLLED, 3-ARM PARALLEL GROUP TRIAL COMPARING CHF 5993 200/6/12.5 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE PLUS GLYCOPYRRONIUM BROMIDE) TO CHF 1535 200/6 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETHASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE) ALONE OR ON TOP OF OPEN-LABEL TIOTROPIUM 2.5 µg RESPIMAT® IN PATIENTS WITH ASTHMA UNCONTROLLED ON HIGH DOSES OF INHALED CORTICOSTEROIDS IN COMBINATION WITH LONG-ACTING ß2-AGONISTS

Conditions
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Asthma

Intervention / Treatment
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* Drug: CHF 5993 200/6/12.5 µg
* Drug: CHF 1535 200/6 µg
* Drug: CHF 1535 200/6 µg + Tiotropium Respimat 2.5 µg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of asthma ≥ 1 year and diagnosed before 40 years old Uncontrolled asthma with double therapy only on high doses of Inhaled CorticoSteroid (ICS) in combination with Long-Acting Beta2 Agonist (LABA) with ACQ-7 (Asthma Control Questionnaire) ≥1.5 Pre-bronchodilator FEV1 <80% of the predicted normal value Positive reversibility test At least 1 documented asthma exacerbation in the previous year Exclusion Criteria: Pregnant or lactating women Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Patients with any asthma exacerbation or respiratory tract infection in the 4 weeks prior screening Current smoker or ex-smoker (>= 10 packs year) Any change in dose, schedule or formulation of ICS + LABA combination in the 4 weeks prior screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF 5993 200/6/12.5 µg<br>Treatment A: CHF 5993 200/6/12.5 µg: 2 inhalations bid Total daily dose: 800/24/50 µg BDP/FF/GB | Drug: CHF 5993 200/6/12.5 µg<br> <br> |
| Active Comparator: CHF 1535 200/6 µg<br>Treatment B: CHF 1535 200/6 µg: 2 inhalations bid Total daily dose: 800/24 µg BDP/FF | Drug: CHF 1535 200/6 µg<br> <br> |
| Active Comparator: CHF 1535 200/6 µg + Tiotropium Respimat 2.5 µg<br>Treatment C (open-label arm): CHF 1535 200/6 µg: 2 inhalations bid + Tiotropium Respimat 2.5 µg: 2 inhalations od Total daily dose: 800/24 µg BDP/FF + 5 µg Tio | Drug: CHF 1535 200/6 µg + Tiotropium Respimat 2.5 µg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-dose FEV1 (Forced Expiratory Volume in the first second) |  | Week 26 | 
| Reduction of moderate and severe asthma exacerbations rate |  | Week 0 to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak FEV1 (Peak of Forced Expiratory Volume in the first second) within 3 hours post-dose |  | Week 26 | 
| Change from baseline in morning PEF (Peak Expiratory Flow) |  | Week 0 to Week 26 | 
| Reduction of severe asthma exacerbations rate | Pooled analysis of CCD-05993AB1-03 and CCD-05993AB2-02 trials | Week 0 to week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Anticholinergics, Triple combination