EFFICACY AND TOLERABILITY OF BECLOMETHASONE DIPROPIONATE 100 µg + FORMOTEROL 6 µg pMDI VIA HFA-134a vs. FLUTICASONE 125 µg + SALMETEROL 25 µg pMDI

This study has been completed.
Sponsor:
Information provided by:
Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier:
NCT00394368
First received: October 30, 2006
Last updated: NA
Last verified: October 2006
History: No changes posted
  Purpose

The aim of this study was to compare the efficacy and tolerability of the fixed combination beclomethasone/formoterol pMDI with that of fluticasone/salmeterol pMDI in patients with moderate to severe asthma


Condition Intervention Phase
Bronchial Asthma
Drug: beclomethasone dipropionate plus formoterol fumarate combination
Drug: fluticasone propionate plus salmeterol xinafoate combination
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: DOUBLE BLIND, 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. FLUTICASONE 125 µg + SALMETEROL 25 µg pMDI (SERETIDE®) IN THE 12-WEEK TREATMENT OF ADULT PATIENTS WITH MODERATE TO SEVERE PERSISTENT ASTHMA

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Further study details as provided by Chiesi Farmaceutici S.p.A.:

Primary Outcome Measures:
  • morning peak expiratory flow (PEF) daily measured by patients

Secondary Outcome Measures:
  • evening PEF measured by patients daily
  • FEV1 measured by patients daily
  • standard pulmonary function tests measured at clinics at 2, 4, 8 and 12 weeks
  • change in FEV1 and PEF from pre-dose to 5, 15, 30 and 60 minutes after study drug intake at week 0 and 12
  • symptoms scores measured by patients daily
  • symptoms’ free days measured by patients daily
  • use of relief salbutamol measured by patients daily
  • frequency of asthma exacerbations evaluated at 2, 4, 8 and 12 weeks
  • adverse events and adverse drug reactions daily
  • ECG (with QTc interval) at 0 and 12 weeks
  • vital signs (heart rate and blood pressure)at 2, 4, 8 and 12 weeks
  • 12-hour (overnight)urinary cortisol/creatinine ratio at week 0 and 12

Estimated Enrollment: 180
Study Start Date: November 2004
Estimated Study Completion Date: September 2005
Detailed Description:

Asthma is a chronic disease that is estimated to affect over 25 million people both in the U.S. and 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 form 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 FLUTICASONE 125 µg + SALMETEROL 25 µg pMDI (SERETIDE®)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of moderate to severe persistent asthma for at least 6 months, according to GINA revised version 2002 guidelines (11):

    • Forced expiratory volume (FEV1) or peak expiratory flow rate (PEFR) ³ 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 mg, 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 ´ 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 ³ 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00394368

Locations
Poland
Outpatients Department of Allergology "Medcare"
Gdansk, Poland
Nzoz "Non nocere"
Gdansk, Poland
Nzoz "Krakow Poludnie" Pulmonologic Policlinic
Krakow, Poland
Specialist Allergy Center All-Med
Krakow, Poland
Private Institute of Health and Beauty
Warszawa, Poland
Dolnoslaski Centre of Medical Diagnostic "Dolmed"
Wroclaw, Poland
Ukraine
Kharkiv City Clinical Hospital 13 Pulmonological Department
Kharkiv, Ukraine
Republican Clinical Hospital, Institute of Phthisiology and Pulmonology, Academy of Medical Science of Ukraine, Pulmonology Department
Kiev, Ukraine
Institute of Phthisiology and Pulmonology, Academy of Medical Science of Ukraine, Depatment of Diagnostic, Therapy and Clinical Pharmacology of Lung Disease
Kiev, Ukraine
Republican Clinical Hospital Institute of Phthisiology and Pulmonology Academy of Medical Science of Ukraine, Clinical Functional Department
Kiev, Ukraine
Department of Hospital Therapy of Lugansk, State Medical Institute Lugansk, Regional Clinical Hospital
Lugansk, Ukraine
Department Therapy of Bronchopulmonary Pathology in Adults, Crimean Republic Research Institute of Physical Methods of Therapy and Medical Climatology
Yalta, Ukraine
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
Investigators
Study Chair: Leonardo M. Fabbri, MD Department of Respiartory Diseases - University of Modena and Reggio Emilia, Modena, Italy
Study Chair: Maurizio A. Vignola, MD Institute of Lung Pathophysiology, National Research Council, Palermo, Italy
  More Information

No publications provided by Chiesi Farmaceutici S.p.A.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00394368     History of Changes
Other Study ID Numbers: MC/PR/033011/001/03
Study First Received: October 30, 2006
Last Updated: October 30, 2006
Health Authority: Poland: Ministry of Health

Keywords provided by Chiesi Farmaceutici S.p.A.:
asthma
combinations
inhaled therapy
corticosteroids
long acting bronchodilators
salmeterol
beclomethasone
formoterol
fluticasone

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Beclomethasone
Formoterol
Salmeterol
Albuterol
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents

ClinicalTrials.gov processed this record on August 28, 2014