A single centre, randomised, double-blind, double-dummy, placebo-and active-controlled, 3-way cross-over study to evaluate the 24 hour FEV1 profile of a single dose of CHF 5188 pMDI (400/4 mcg QD) (fixed combination budesonide/carmoterol 200/2 mcg) in adults patients with moderate or severe persistent asthma

• Conditions: MedDRA version: 9.1Level: LLTClassification code 10003555Term: Asthma bronchial; Moderate or Severe Persistent Asthma

• Registration Number: EUCTR2008-001773-15-GB
• Lead Sponsor: Chiesi Farmaceutici SpA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-15
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1. Written Informed Consent Obtained
2. Male or female patients aged > or = 18 years
3. Patients with moderate or severe asthma not optimally controlled according to the GINA 2005 classification of asthma severity by daily medication regimen and response to treatment
4. Patients already treated with inhaled cortiscosteroids at stable dose for at least 4 weeks prior to inclusion
5. Patients with Forced Expiratory Volume in the first second (FEV1) = 50% and = 90% of predicted for the patient normal value and not less than 0.9 L in absolute value
6. Patients with a documented positive response to the reversibility test, defined as an increase of at least 12% and at least 200 mL from pre-dosing values in the measurement of FEV1 within 30 minutes after the inhalation of 400 µg salbutamol pMDI
7. Patients with a co-operative attitude and ability to be trained to correctly use the pMDI and the Turbuhaler®.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients will not be enrolled at Visit 1 into the run-in period if they meet any of the following criteria:
1. Inability to carry out pulmonary function testing;
2. Diagnosis of COPD as defined by the current GOLD guidelines;
3. Current smokers or ex-smokers with total cumulative exposure equal or more than 5 pack-years and/or having stopped smoking one year or less prior to study start;
4. History of near fatal asthma or of a past hospitalisation for asthma in ICU;
5. Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 4 weeks (e.g. oral corticosteroids intake);
6. Patients presenting with 3 or more asthma exacerbations in the previous year;
7. Hospitalisation due to asthma during the previous 8 weeks;
8. History of significant seasonal variation of asthma;
9. Patients treated with oral or intravenous corticosteroids in the past 4 weeks or depot injectable corticosteroids in the past 8 weeks;
10.Patients had used any of the following medications prior to screening and has not met the specified minimum wash-out period:
-short-acting ß2-agonists : 6 hours,
-long-acting ß2-agonists : 1 week,
-short-acting anticholinergics : 12 hours,
-long-acting anticholinergics (i.e. tiotropium bromide): 1 week,
-leukotriene modifiers : 4 weeks,
-fixed combinations of an anti-cholinergic and short-acting ß2 agonist (e.g. Duovent® and Berodual®) :12 hours,
-fixed combinations of an inhaled corticosteroid and long-acting ß2-agonist (e.g. Seretide®, Symbicort®) : 1 week,
-oral or nebulised bronchodilators : 4 weeks,
-nebulised corticosteroids : 4 weeks,
-xanthine derivative (e.g. theophylline) any formulation: 4 weeks,
-sodium cromoglycate or nedocromil sodium : 4 weeks;
11. Patients with a history or current evidence of heart failure, coronary artery disease, myocardial infarction, severe uncontrolled hypertension, cardiac arrhythmias or any other significant cardiovascular disease;
12. Patients presenting with a clinically significant abnormality at a 12-lead ECG or presenting a QTcB interval in ECG > 450msec (males) or > 470msec (females);
13. Patients presenting with serum potassium < 3.5 mmol/L or > 6.0mmol/L;
14. Patients presenting with fasting serum glucose > 8 mmol/L;
15. Patients with a clinically significant or uncontrolled concomitant disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant pulmonary disease (e.g. tuberculosis, lung cancer or other), gastrointestinal disease (e.g. active peptic ulcer or other), neurological disease, haematological disease, autoimmune disorders or other;
16. Patients with active cancer or a history of cancer with less than 5 years disease free survival time or any other chronic disease with poor prognosis and /or affecting patient status;
17. Pregnant or lactating females or females at risk of pregnancy, i.e. those not making use of an effective contraceptive method (oral contraception, IUD, double barrier method (spermicide + condoms or spermicide + diaphragm), tubal ligature). A pregnancy test will be performed at screening in women of childbearing potential;
18. Post-menopausal female not having amenorrhoea for at least 1 year;
19. Patients with a history of alcohol or drug abuse;
20. Patients with a known intolerance/hypersensitivity to beta2-aderenergic agonists, propellant gases/excipients;
21. Patients unlikely to comply with the protocol or una

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that CHF 5188, given once daily in the morning to moderate or severe asthmatic patients, maintains the bronchodilatator effect over the 24 hours interval;Secondary Objective: - to compare the efficacy of CHF 5188 with that of Symbycort 200/6 mcg given twice daily (TDD 400/12 mcg)<br>- to monitor safey and tolerability;Primary end point(s): - Through FEV1 (mean 23h-24h FEV1)