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®)

NCT ID: NCT00413387

Last Updated: 2020-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-30
• Study Completion Date: 2005-10-31

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).

Conditions

Bronchial Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

chf1535

Group Type: EXPERIMENTAL

beclomethasone dipropionate plus formoterol fumarate combination

Intervention Type: DRUG

100mcg beclomethasone diproprionate plus 6 mcg formoterol

2

Symbicort

Group Type: ACTIVE_COMPARATOR

budesonide plus formoterol combination

Intervention Type: DRUG

200mcg budesonide plus 6 mcg formoterol

Interventions

beclomethasone dipropionate plus formoterol fumarate combination

100mcg beclomethasone diproprionate plus 6 mcg formoterol

Intervention Type: DRUG

budesonide plus formoterol combination

200mcg budesonide plus 6 mcg formoterol

Intervention Type: DRUG

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

• 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.

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Chiesi Farmaceutici

Principal Investigators

Leonardo M. Fabbri, MD

Role: STUDY_CHAIR

Department of Resipiratory Diseases - University of Modena and Reggio Emilia, Modena, Italy

Maurizio A. Vignola, MD

Role: STUDY_CHAIR

Institute of Lung Pathophysiology, National Research Council, Palermo, Italy

Locations

Ambulance For Paediatric and Pulmonology

Vienna, , 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

Kharkiv, , 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

Countries

Austria; Poland; Ukraine

References

Papi A, Paggiaro PL, Nicolini G, Vignola AM, Fabbri LM; Inhaled Combination Asthma Treatment versus SYmbicort (ICAT SY) Study Group. Beclomethasone/formoterol versus budesonide/formoterol combination therapy in asthma. Eur Respir J. 2007 Apr;29(4):682-9. doi: 10.1183/09031936.00095906. Epub 2006 Nov 15.

Reference Type: RESULT

PMID: 17107988 (View on PubMed)

Other Identifiers

MC/PR/033011/002/03

Identifier Type: -

Identifier Source: org_study_id