Patient with severe asthma MedDRA version: 9.1 Level: LLT Classification code 10003553 Term: Asthma
Conditions
Interventions
Product Name: CHF 1535 HFA pMDI
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: beclometasone dipropionate
CAS Number: 5534-09-8
Other descriptive name: BDP
Concentration un
Sponsors
CHIESI FARMACEUTICI S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient will be enrolled at Visit 1 into the run-in period if they meet each and every one of the following criteria: 1. Subject’s written informed consent and written informed consent by parents/legal representatives (adolescent patients). 2. Outpatients of both sexes aged = 18 and = 70 years. 3. Evidence of asthma demonstrated by a documented positive response to the reversibility test, defined as ?FEV1 = 12% and = 200 mL over baseline, within 30 minutes after administration of 400 µg of salbutamol pMDI. In case this is not achieved, a historically documented FEV1 reversibility within the previous 12 months is acceptable. 4. Patients with severe persistent asthma diagnosed according to GINA guidelines (revised 2006). 5. Levels of asthma control, during each of the two previous weeks (to be checked at screening and at randomisation visits), defined as: ? 1 or more of the following: - Daytime symptoms ? more than twice/ week; - Limitations of activities ? any; - Nocturnal symptoms/awakening ? any; - Need for reliever/rescue treatment ? more than twice/ week. 6. Patients on previous treatment with high doses of ICS (> 1000 µg BDP CFC daily or equivalent) or ICS + LABA fixed or free combinations (daily dose of budesonide 800 µg/fluticasone 500 µg or equivalent ICS doses plus formoterol 24 µg or salmeterol 100µg) at a stable dose for at least 2 months prior to inclusion. 7. Patients who meet the following requirement: FEV1 = 40% and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patient will not be enrolled at Visit 1 into the run-in period and will not be randomized to treatments at Visit 2 (i.e. these criteria will be also reviewed at Visit 2) if they meet one or more of the following criteria: 1. Pregnant or lactating women. Females of childbearing potential without an efficient contraception (e.g. oestro-progestatives, condoms). 2. Having received an investigational drug within 2 months. 3. Inability to comply with study procedures or with study treatment intake. 4. Seasonal asthma or asthma occurring only during episodic exposure to an allergen or a chemical sensitizer. 5. History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease. 6. Patients who suffer from COPD as diagnosed by the GOLD guidelines (2006). 7. Previous or current smokers who have a smoking history greater than 5 pack years, (defined as the number of packs of 20 cigarettes smoked per day multiplied by number of years the patient smoked). 8. Diagnosis of restrictive lung disease (e.g. kyphoscoliosis, ankylosing spondylitis). 9. Patients who have an uncontrolled cardiovascular (e.g., uncontrolled hypertension), respiratory, hematologic, immunologic, renal, neurologic, hepatic, endocrine (e.g., uncontrolled diabetes mellitus) or other disease, or any condition that might, in the judgment of the Investigator, place the patients at undue risk or potentially compromise the results or interpretation of the study. 10. Patients who have a history of coronary artery disease, cerebrovascular disease, and cardiac arrhythmias. 11. Patients who have a concomitant disease of poor prognosis (e.g., cancer). 12. Patients who have a serum potassium value = 3.5 mEq/L or > 5.5 mEq/L and/or a fasting serum glucose value = 140 mg/dL. 13. Patients who have an abnormal QTc interval value in the Screening visit ECG test (i.e., > 450 msec in males or > 470 msec in females). 14. Patients having received a live-attenuated virus vaccination within two weeks prior to screening or during the run-in. 15. Patients mentally or legally incapacitated. 16. Patients who abuse alcohol. 17. Intolerance/hypersensitivity or contra-indication to treatment with ß2-agonists and/or inhaled corticosteroids. 18. Major surgery in the previous 3 months. 19. Any change in dose, schedule, formulation or product of previous ICS or fixed/free combination ICS + LABAs in the 2 months prior to screening visit. 20. Any change in dose, schedule, formulation or product of other concomitant asthma treatments in the 2 months prior to screening visit. 21. Moderate/severe exacerbations and/or intake of oral corticosteroids during the 2-week run-in period. 22. Patients treated with slow-release corticosteroids in the 3 months prior to screening visit. 23. Patients treated with non-potassium sparing diuretics, beta-blocking drugs, quinidine, quinidine-like anti arrhythmics, or any medication with a QTc prolongation potential or a history of QTc prolongation. 24. Patients treated with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants, unless already taken at stable doses at the screening visit. 25. Patients who are receiving therapy that could interact with steroids, such as enzyme inhibitors (macrolide antibiotics, antifungal oral therapy) or induced (anticonvulsants, rifampin). 26. Patients being treated with anti-IgE antibodies. 27. Patients who have had a respiratory tract infection within 2-months prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Two co-primary variables are defined: - Change from baseline to end of treatment in pre-dose morning FEV1 (L) (measured at clinic visit). - Change from baseline to end of treatment in percentage of complete days without asthma symptoms (asthma symptom scores recorded daily at home on electronic peak flow meter).;Main Objective: In symptomatic patients on high-doses ICS (Inhaled Corticosteroid) beclomethasone diproprionate (two puffs b.i.d.), to demonstrate the superiority of CHF 1535 200/6 (two puffs b.i.d.) versus a high dose of BDP (beclomethasone diproprionate 2000 µg/day) given as monotherapy, in terms of pulmonary function (change from baseline in pre-dose morning FEV1 measured at clinic) and asthma control (change from baseline in percentage of complete days without asthma symptoms), and the non-inferiority versus Seretide® 500/50 (one inhalation b.i.d.), in terms of pulmonary function (change from baseline in pre-dose morning FEV1 measured at clinic) during a 24-week treatment period.;Secondary Objective: To evaluate the effect of the treatments on additional lung function parameters and clinical outcome measures, to assess the achievement of asthma control (according to the criteria established in GINA revised 2006), to assess the safety and the tolerability of CHF 1535 200/6 and to perform a pharmaco-economic evaluation in the perspective of the HealthCare System. | — |
Countries
Bulgaria, Czech Republic, Estonia, France, Germany, Italy, Latvia, Lithuania, Slovenia, Spain
Outcome results
None listed