EFFICACY AND TOLERABILITY OF BECLOMETHASONE DIPROPIONATE 100 �g + FORMOTEROL 6 �g pMDI VIA HFA-134a vs. FLUTICASONE 125 �g + SALMETEROL 25 �g pMDI
Information source: Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bronchial Asthma
Intervention: beclomethasone dipropionate plus formoterol fumarate combination (Drug); fluticasone propionate plus salmeterol xinafoate combination (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Chiesi Farmaceutici S.p.A. Official(s) and/or principal investigator(s): Leonardo M. Fabbri, MD, Study Chair, Affiliation: Department of Respiartory Diseases - University of Modena and Reggio Emilia, Modena, Italy Maurizio A. Vignola, MD, Study Chair, Affiliation: Institute of Lung Pathophysiology, National Research Council, Palermo, Italy
Summary
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
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: morning peak expiratory flow (PEF) daily measured by patients
Secondary outcome: evening PEF measured by patients dailyFEV1 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
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
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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.
Locations and Contacts
Nzoz "Non nocere", Gdansk, Poland
Outpatients Department of Allergology "Medcare", 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
Kharkiv City Clinical Hospital 13 Pulmonological Department, Kharkiv, 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
Republican Clinical Hospital, Institute of Phthisiology and Pulmonology, Academy of Medical Science of Ukraine, Pulmonology 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
Additional Information
Starting date: November 2004
Last updated: October 30, 2006
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