Efficacy and Tolerability of Beclomethasone Dipropionate 100 µg + Formoterol 6 µg pMDI Via HFA-134a Vs. Budesonide 160 µg + Formoterol 4,5 µg Dry Powder Via Turbuhaler®. (Symbicort®)
Overview[ - collapse ][ - ]
| Purpose | The aim of this study was to compare the efficacy and tolerability of the fixed combination beclomethasone/formoterol pMDI with that of budesonide/formoterol dry powder via Turbuhaler. |
|---|---|
| Condition | Bronchial Asthma |
| Intervention | Drug: beclomethasone dipropionate plus formoterol fumarate combination Drug: budesonide plus formoterol combination |
| Phase | Phase 3 |
| Sponsor | Chiesi Farmaceutici S.p.A. |
| Responsible Party | Chiesi Farmaceutici S.p.A. |
| ClinicalTrials.gov Identifier | NCT00413387 |
| First Received | December 18, 2006 |
| Last Updated | April 21, 2008 |
| Last verified | April 2008 |
Tracking Information[ + expand ][ + ]
| First Received Date | December 18, 2006 |
|---|---|
| Last Updated Date | April 21, 2008 |
| Start Date | September 2004 |
| Estimated Primary Completion Date | October 2005 |
| Current Primary Outcome Measures | Morning Peak Expiratory Flow (PEF) daily measured by patients. [Time Frame: morning approximately 8:00] [Designated as safety issue: No] |
| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | Efficacy and Tolerability of Beclomethasone Dipropionate 100 µg + Formoterol 6 µg pMDI Via HFA-134a Vs. Budesonide 160 µg + Formoterol 4,5 µg Dry Powder Via Turbuhaler®. (Symbicort®) |
|---|---|
| Official Title | Double Blind, Double Dummy, Multinational, Multicentre, Parallel-Group Design Clinical Trial of the Efficacy and Tolerability of CHF 1535 (Beclomethasone Dipropionate 100 µg + Formoterol 6 µg) pMDI Via HFA-134a Vs. Budesonide 160 µg + Formoterol 4,5 µg Dry Powder Via Turbuhaler® (Symbicort®) in the 12-Week Treatment of Adult Patients With Moderate to Severe Persistent Asthma |
| Brief Summary | The aim of this study was to compare the efficacy and tolerability of the fixed combination beclomethasone/formoterol pMDI with that of budesonide/formoterol dry powder via Turbuhaler. |
| Detailed Description | Asthma is a chronic disease that is estimated to affect over 25 million people both in the U.S. and in Europe (i.e. approximately 10% of the total population). Pharmacological therapy is used to treat reversible airway obstruction, inflammation and hyper-reactivity. Medications include preventive treatments in forms of antinflammatory/antiallergic agents (i.e. glucocorticosteroids, leukotriene antagonists, cromolyn sodium) and reliever treatments, in forms of bronchodilators (i.e. β-adrenergic agonists, anticholinergics). In patients treated with inhaled glucocorticosteroids whose asthma is not fully controlled, national and international guidelines recommend a stepwise approach. Recent evidence-based clinical trials show that the addition of a LABA to inhaled glucocorticosteroids is more beneficial in terms of asthma control than increasing the dose of corticosteroids alone. COMPARISONS: CHF 1535 (BECLOMETHASONE DIPROPIONATE 100 µg+ FORMOTEROL 6 µg) pMDI via HFA-134a compared to SYMBICORT (BUDESONIDE 160 µg + FORMOTEROL 4,5 µg). |
| Study Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
| Condition | Bronchial Asthma |
| Intervention | Drug: beclomethasone dipropionate plus formoterol fumarate combination 100mcg beclomethasone diproprionate plus 6 mcg formoterol Drug: budesonide plus formoterol combination 200mcg budesonide plus 6 mcg formoterol |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 219 |
| Estimated Completion Date | October 2005 |
| Estimated Primary Completion Date | August 2005 |
| Eligibility Criteria | Inclusion Criteria: - Clinical diagnosis of moderate to severe persistent asthma for at least 6 months, according to GINA revised version 2002 guidelines: - Forced expiratory volume (FEV1) or peak expiratory flow rate (PEFR) > 50% and < 80% of the predicted normal; - Asthma not adequately controlled with the current therapies, defined as presence of daily asthma symptoms > once a week and night-time asthma symptoms > twice a month, and daily use of short-acting β2-agonists. These findings are to be based on recent medical history and are to be confirmed in the 2-week run-in period. - Treatment with inhaled corticosteroids at a daily dose ≤ 1000 μg of BDP or equivalent. The daily dose of inhaled corticosteroids taken at visit 1 will be assessed taking into account the following ratios between the doses of the different steroids: fluticasone propionate : BDP CFC = 1 : 2; budesonide : BDP CFC = 4 : 5; flunisolide : BDP CFC = 1 : 1. The ratios between inhaled steroids are irrespective of the formulations (i.e. spray aerosol or powder) used. When BDP is given in the new extra-fine HFA-134a formulation (as QVAR®, 3M Healthcare), the ratio with BDP CFC is set as 2 : 5. Therefore, the maximum allowed daily dose of inhaled corticosteroids at study entry will be: budesonide 800 μg, fluticasone propionate 500 μg, flunisolide 1000 μg, BDP 1000 mcg, BDP HFA extra-fine 400 μg. - Positive response to the reversibility test in the screening visit, defined as an increase of at least 12% (or, alternatively, of 200mL) from baseline value in the measurement of FEV1 30 minutes following 2 puffs (2 x 100 µg) of inhaled salbutamol administered via pMDI. The reversibility test can be avoided in patients having a documented positive response in the previous 6 months. - A co-operative attitude and ability to be trained to correctly use the metered dose inhalers and to complete the diary cards. - Written informed consent obtained. - At the end of the 2-week run-in period, the presence of daily asthma symptoms (of at least mild intensity) and nighttime asthma symptom (of at least mild intensity) > once a week, as well as of daily use of relief salbutamol is to be confirmed by reviewing the diary cards for run-in Exclusion Criteria: - Inability to carry out pulmonary function testing; - Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) as defined by the National Heart Lung and Blood Institute/World Health Organisation (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (30); - History of near fatal asthma; - Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 8 weeks; - Three or more courses of oral corticosteroids or hospitalisation due to asthma during the previous 6 months; - Patients treated with long-acting β2-agonists, anticholinergics and antihistamines during the previous 2 weeks, with topical or intranasal corticosteroids and leukotriene antagonists during the previous 4 weeks; - Patients who have changed their dose of inhaled corticosteroids during the previous 4 weeks, or treatment with inhaled corticosteroids at a daily dose > 1000 μg of BDP or equivalent (except for extra-fine formulations, see inclusion criteria); - Current smokers or recent (less than one year) ex-smokers, defined as smoking at least 10 cigarettes/day; - History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe hypertension, cardiac arrhythmias; - Diabetes mellitus; - Percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass graft (CABG) during the previous six months; - Patients with an abnormal QTc interval value in the ECG test, defined as > 450 msec in males or > 470 msec in females; - Other haemodynamic relevant rhythm disturbances (including atrial flutter or atrial fibrillation with ventricular response, bradycardia (≤ 55 bpm), evidence of atrial-ventricular (AV) block on ECG of more than 1st degree; - Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g. active peptic ulcer), neurological or haematological autoimmune diseases; - Cancer or any chronic diseases with prognosis < 2 years; - Pregnant or lactating females or females at risk of pregnancy, i.e. those not demonstrating adequate contraception (i.e. barrier methods, intrauterine devices, hormonal treatment or sterilization). A pregnancy test is to be carried out in women of a fertile age. - History of alcohol or drug abuse; - Patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers as regular use; - Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients; - Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study; - Patients who received any investigational new drug within the last 12 weeks; - Patients who have been previously enrolled in this study; - At the end of the run-in period, patients will not be admitted to the treatment period in the case of an increase of PEFR (L/sec) measured at the clinics at the end of the run-in period > 15% in respect of values measured at the start of the run-in period; - Patients with asthma exacerbations during the run-in period will also be excluded from the study. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | Austria, Poland, Ukraine |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00413387 |
|---|---|
| Other Study ID Numbers | MC/PR/033011/002/03 |
| Has Data Monitoring Committee | No |
| Information Provided By | Chiesi Farmaceutici S.p.A. |
| Study Sponsor | Chiesi Farmaceutici S.p.A. |
| Collaborators | Not Provided |
| Investigators | Study Chair: Leonardo M. Fabbri, MD Department of Resipiratory Diseases - University of Modena and Reggio Emilia, Modena, ItalyStudy Chair: Maurizio A. Vignola, MD Institute of Lung Pathophysiology, National Research Council, Palermo, Italy |
| Verification Date | April 2008 |
Locations[ + expand ][ + ]
| Ambulance For Paediatric and Pulmonology | Wien, Austria |
|---|---|
| Nzoz "Medex"Poradnia Alergologiczna | Bielsko-Biala, Poland |
| Centrum Uslug Medycznych | Krakow, Poland |
| Centrum Alergologii | Lodz, Poland |
| Prywatny Gabinet Lekarski | Lodz, Poland |
| Uniwersytet Medyczny | Lodz, Poland |
| Nzoz Lekarze Specjalisci | Wroclaw, Poland |
| Internal Medicine Department, Dniepropetrovsk State Medical Academy. City Clinical Hospital no. 4 | Dniepropetrovsk, Ukraine |
| Institute of Therapy, Ukranian Academy of Medical Science. Pulmonological Departement | Kharkiv, Ukraine |
| Kharkov Regional Clinical Hospital. Pulmonological and Allergological Department | Kharkov, Ukraine |
| Institute of Phthisiology and Pulmonology Academy of Medical Science of the Ukraine, Pulmonology Departement | Kiev, Ukraine |
| Institute of Phthisiology and Pulmonology Academy of Medical Science of the Ukraine. Department of Diagnostic, Therapy and Clinical Pharmacology of Lung Diseases | Kiev, Ukraine |
| Kiev Medical Academy of Postdiploma Education. Department of Medical Genetics, Clinical Immunology and Allergology | Kiev, Ukraine |