Official Title: “Prospective, Randomised, Open-Label, Multicentre, Active Drug Controlled, Parallel Group Design Clinical Trial of the Efficacy and Safety of Beclomethasone Dipropionate 400 Mcg + Formoterol 24 Mcg pMDI Via HFA-134a (Foster™) vs. Fluticasone Propionate 500 Mcg + Salmeterol Xinafoate 100 Mcg DPI (Seretide Diskus®) in the 6 Months Stepdown Treatment of Adult Patients With Controlled Asthma”

Asthma is a serious global health problem. People of all ages in countries throughout the world are affected by this chronic airway disorder that can be severe and sometimes fatal.

The prevalence of asthma is increasing everywhere, especially among children.According to international guidelines, once control of asthma is achieved and maintained for at least 3 months, a gradual reduction of the maintenance therapy should be tried in order to identify the minimum therapy required to maintain control. This will help reduce the risk of side effects and enhance patient adherence to the treatment plan.

Reduction of therapy in patients on combination therapy should begin with a reduction in the dose of inhaled glucocorticosteroid.1 The present study is designed to evaluate if patients with controlled asthma treated with FP 1000 mcg + salmeterol 100 mcg daily can be stepped down. Stepping-down will be attempted with two medications: a new combination of extrafine beclomethasone dipropionate 400 mcg + formoterol 24 mcg daily (test medication, Foster™) and, alternatively, fluticasone propionate 500 mcg + salmeterol 100 mcg daily(reference medication) without losing asthma control.If this hypothesis will be confirmed, the present study will demonstrate that asthma control can be maintained with less than half the dose of inhaled corticosteroid and with less medical costs.

Given the aims of this study, the population to be monitored includes adult patients with moderate persistent asthma, which can be defined controlled according to the current guidelines under standard stabilised treatment. The intended treatment duration is therefore designed to ensure that good control of asthma is firmly achieved before stepping down the treatment (8 weeks run-in period), but also that the condition of the patients are followed long enough (24 weeks comparative treatment period) to ensure that a new stable condition is also obtained and properly monitored.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: September 2009

Intervention(s) in this Clinical Trial

• Drug: Beclomethasone plus formoterol fixed combination
  • 100+6 pMDI
• Drug: Fluticasone plus salmeterol fixed combination
  • diskus 250/50

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Foster
• Active Comparator: 2
  • Seretide

Primary Measures

• Morning pre-dose PEF measured daily by patients (mean of the last 2 weeks of treatment period).
  • Time Frame: mean of the last 2 weeks of treatment period
    Safety Issue?: No

Secondary Measures

• symptom scores and symptom free days
  • Time Frame: in the whole study period and every 2-week period
    Safety Issue?: No
• morning and evening pre-dose PEF and FEV1 measured daily by patients;
  • Time Frame: daily and mean each 2-week period
    Safety Issue?: No
• pulmonary function tests measured at clinics (pre-dose PEF, FVC and FEV1);
  • Time Frame: at aech clinic visit
    Safety Issue?: No
• change of FEV1 from pre-dose to 5, 15, 30 and 60 minutes post-dose;
  • Time Frame: randomization visit and end of treatment visit
    Safety Issue?: No
• number, frequency and severity of exacerbations, time to first exacerbation
  • Time Frame: whole study period
    Safety Issue?: No
• adverse events and adverse drug reactions
  • Time Frame: retrospectively assessed at each visit
    Safety Issue?: Yes
• use of relief salbutamol and days without use of relief salbutamol;
  • Time Frame: daily
    Safety Issue?: No
• proportion of patients with controlled asthma and partly controlled asthma, weeks of controlled asthma and partly controlled asthma;
  • Time Frame: weekly
    Safety Issue?: No
• pharmaco-economic analysis of medical and non medical costs.
  • Time Frame: during study period
    Safety Issue?: No
• 12 h-overnight urinary cortisol/creatinine
  • Time Frame: (collected at visit 3, 6 and 9)
    Safety Issue?: Yes
• vital signs
  • Time Frame: at each visit
    Safety Issue?: Yes

Inclusion Criteria:

• Patients will be enrolled for screening at Visit 1 into the run-in period if they meet all the following criteria:
• Clinical diagnosis of moderate persistent asthma for at least 6 months, according to GINA revised version 2005 guidelines 1 and considering current treatment;
• Forced expiratory volume (FEV1) or peak expiratory flow rate (PEFR) ≥ 80% of the predicted normal value;
• Treated with fluticasone 1000 mcg + salmeterol 100 mcg daily for at least 4 weeks at a stable dose;
• Reporting no nocturnal symptoms or awakenings, no exacerbations, no limitations of activities, symptoms in ≤2 days and use of rescue medication ≤2 days per week, in the last 4 weeks;
• Exhibiting a co-operative attitude and ability to be trained to correctly use the study devices and to complete the diary cards.
• At the end of run in period (Week 8+0; Visit 3), patients will be recruited into the treatment period and randomized to treatment if they meet the following criterion:
• Asthma is controlled 1 in each of the last 4 weeks of run-in (no nocturnal symptoms or awakenings; no exacerbations; no limitations of activities; symptoms in ≤2 days; use of rescue medication ≤2 days; morning PEF ≥80% of predicted in every day) confirmed by reviewing the diary cards.

Exclusion Criteria:

• Inability to carry out pulmonary function testing;
• Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) as defined by the NHLBI/WHO's GOLD guidelines;
• Current smokers or recent (less than one year) ex-smokers with a smoking history of ≥10 pack/years;
• History of near fatal asthma;
• Evidence of 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 anticholinergics and antihistamines during the previous 2 weeks, with topical or intranasal corticosteroids and leukotriene antagonists during the previous 4 weeks;
• History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe hypertension, cardiac arrhythmias;
• Diabetes mellitus;
• PTCA or 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;
• 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 who received any investigational new drug within the last 12 weeks;
• At the end of run in period (Week 8+0; Visit 3), patients will not be randomized to treatment if they do not completely meet the definition of "controlled asthma". These subjects will be considered screening failures and will not count against the planned number to be recruited.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Chiesi Farmaceutici S.p.A.

Overall Clinical Trial Officials and Contacts

Pierluigi Paggiaro, MD Principal Investigator Ospedale Cisanello, Pisa  

Overall Contact: Pierluigi Paggiaro, MD 050995366 

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00497237

Study ID Number: MC/PR/033011/005/06

ClinicalTrials.gov Identifier: NCT00497237

Health Authority: Italy: Ministry of Health