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®)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00413387
Recruitment Status : Completed
First Posted : December 19, 2006
Last Update Posted : April 22, 2008
Information provided by:
Chiesi Farmaceutici S.p.A.

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.

Condition or disease Intervention/treatment Phase
Bronchial Asthma Drug: beclomethasone dipropionate plus formoterol fumarate combination Drug: budesonide plus formoterol combination Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 219 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : September 2004
Actual Primary Completion Date : August 2005
Actual Study Completion Date : October 2005

Arm Intervention/treatment
Experimental: 1
Drug: beclomethasone dipropionate plus formoterol fumarate combination
100mcg beclomethasone diproprionate plus 6 mcg formoterol

Active Comparator: 2
Drug: budesonide plus formoterol combination
200mcg budesonide plus 6 mcg formoterol

Primary Outcome Measures :
  1. Morning Peak Expiratory Flow (PEF) daily measured by patients. [ Time Frame: morning approximately 8:00 ]

Secondary Outcome Measures :
  1. Evening PEF measured by patients daily. [ Time Frame: evening approximately 20:00 ]
  2. FEV1 measured by patients daily. [ Time Frame: morning and evening ]
  3. Standard pulmonary function tests measured at clinics at 2, 4, 8 and 12 weeks. [ Time Frame: morning before drug intake ]
  4. Change in FEV1 and PEF from pre-dose to 5, 15, 30 and 60 minutes after study drug intake at week 0 and 12. [ Time Frame: morning post drug intake ]
  5. Symptoms scores measured by patients daily. [ Time Frame: morning and evening ]
  6. symptoms'free days measured by patients daily. [ Time Frame: daily ]
  7. Use of relief salbutamol measured by patients daily. [ Time Frame: daily ]
  8. Frequency of asthma exacerbations evaluated at 2, 4, 8 and 12 weeks. [ Time Frame: morning of the visits retrospective assessment ]
  9. Adverse event and adverse drug reaction daily. [ Time Frame: morning of visits retrospective assesment ]
  10. ECG (with QTc interval)at 0 and 12 weeks. [ Time Frame: morning of start and end of treatment visits ]
  11. Vital signs (heart rate and blood pressure) at 2, 4, 8 and 12 weeks [ Time Frame: morning of visits ]
  12. Use of relief salbutamol. [ Time Frame: daily ]
  13. Frequency of asthma exacerbations. [ Time Frame: at visits ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00413387

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
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
Study Chair: Leonardo M. Fabbri, MD Department of Resipiratory Diseases - University of Modena and Reggio Emilia, Modena, Italy
Study Chair: Maurizio A. Vignola, MD Institute of Lung Pathophysiology, National Research Council, Palermo, Italy

Responsible Party: Gabriele Nicolini, Chiesi Farmaceutici Identifier: NCT00413387     History of Changes
Other Study ID Numbers: MC/PR/033011/002/03
First Posted: December 19, 2006    Key Record Dates
Last Update Posted: April 22, 2008
Last Verified: April 2008

Keywords provided by Chiesi Farmaceutici S.p.A.:
Inhaled therapy
Long acting bronchodilators

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Formoterol Fumarate
Budesonide, Formoterol Fumarate Drug Combination
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists