Uncontrolled asthma MedDRA version: 19.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Chiesi Farmaceutici S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient’s written informed consent obtained prior to any study-related procedures. 2. Male or female patients aged greater than or equal to 18 and =75 years. 3. Patients must have a documented history of asthma for at least 1 year and asthma must have been diagnosed before the patient’s age of 40. 4. Patients with uncontrolled asthma with double therapy only on medium doses of ICS (>500-1000 µg daily dose BDP non-extrafine or estimated clinical comparable dose) in combination with a ß2 longacting bronchodilator (LABA) at a stable dose for at least 4 weeks prior to screening. LABA daily dose: patients under formoterol 24 µg or salmeterol 100 µg or vilanterol 25 µg or other approved dose of LABA as clinically comparable to the others in the list can be included. 5. Patients with a pre-bronchodilator FEV1 12% and >200mL over baseline 10-15 minutes after inhaling 400 µg of salbutamol pMDI. 7. Patients with uncontrolled asthma evidenced by a score at the Asthma Control Questionnaire 7 © (ACQ-7) =1.5 (this criterion must be met at screening and at the end of the run-in period). 8. A documented history of one or more asthma exacerbations requiring treatment with systemic corticosteroids or emergency department visit or in-patient hospitalization in the previous 12 months. 9. A co-operative attitude and ability: ?- to be trained to correctly use the pMDI inhalers; ?- to perform all trial related procedures including technically acceptable pulmonary function tests; ?- to correctly use the electronic diary/peak flow meter. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 861 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 287
Exclusion criteria
Exclusion criteria: 1. Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake. 2. Run-in compliance 450 ms for males or QTcF >470 ms for females at screening or at randomisation visits (criterion not applicable for patient with pacemaker or permanent atrial fibrillation). 14. Patients with a medical history or current diagnosis of narrow-angle glaucoma, symptomatic prostatic hypertrophy, urinary retention bladder neck obstruction that, in the opinion of the investigator, would prevent use of anticholinergic agents. 15. Other severe acute or chronic medical or malignancy or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 16. Patients having received a vaccination within 2 weeks prior to screening or during the run-in. 17. Patients mentally or legally incapacitated, or patients accommodated in an establishment as a result of an official or judicial order. 18. Patients with a history of alcohol or drug abuse within two years prior to the start of the study. 19. Patients with known intolerance/hypersensitivity or contra-indication to treatment with ß2-agonists, inhaled corticosteroids, anticholinergics or propellant gases/excipients. 20. Patients with major surgery in the 3 months prior to screening visit or planned surgery during the trial. 21. Patients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): - Change from baseline in pre-dose FEV1 at Week 26 - Moderate and severe exacerbations rate over 52 weeks of treatment ;Timepoint(s) of evaluation of this end point: 26 weeks and 52 weeks; Main Objective: - To demonstrate the superiority of CHF 5993 100/6/12.5 pMDI compared to CHF 1535 100/6 pMDI in terms of change from baseline in pre-dose FEV1 at Week 26. - To demonstrate the reduction of moderate and severe asthma exacerbations rate with CHF 5993 100/6/12.5 pMDI compared to CHF 1535 100/6 pMDI during the entire 52-week treatment period. ; Secondary Objective: Key Secondary Objectives: - To demonstrate the superiority of CHF 5993 100/6/12.5 pMDI compared to CHF 1535 100/6 pMDI in terms of change from baseline in peak FEV1 within 3 hours post-dose at Week 26. - To demonstrate the superiority of CHF 5993 100/6/12.5 compared to CHF 1535 100/6 in terms of change from baseline in morning PEF averaged over 26-week treatment period. - To demonstrate the reduction of severe asthma exacerbations rate with CHF 5993 100/6/12.5 pMDI compared to CHF 1535 100/6 pMDI during the entire 52-week treatment period in the pooled analysis of CCD-05993AB1-03 and CCD-05993AB2-02 trials. Secondary Objectives - To perform a population PK analysis (in a subset of patients treated with CHF 5993 pMDI) investigating the inter-subject variability in the drug exposure and the effects of selected covariates on PK parameters of BDP, FF and GB. - To assess the safety and tolerability of the study treatments. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in peak FEV1 (within 3 hours post dosing) at Week 26. - Change from baseline in morning PEF measured by patients at home over the 26-week treatment period. - Severe exacerbations rate over 52 weeks of treatment in a pre-specified pooled analysis of the two pivotal studies CCD-5993AB1-03 and CCD-05993AB2-02 - PK analysis - Safety variables, AEs, ADRs ; Timepoint(s) of evaluation of this end point: 26 weeks and 52 weeks Plasma levels measured in week 4 & 40 Safety throughout the study | — |
Countries
Argentina, Belarus, Bulgaria, Czech Republic, Germany, Hungary, Italy, Lithuania, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Ukraine, United Kingdom
Contacts
Public ContactClinical Project Manager
Chiesi Farmaceutici S.p.A.
Outcome results
None listed