Formoterol-HFA 3-month Study in Chronic Obstructive Pulmonary Disease (COPD) Patients

A 3-month, Double-blind, Double-dummy, Randomised, Multinational, Multicenter, 2-arm Parallel-group Study Comparing the Efficacy and Safety of Formoterol-HFA pMDI 12µg Twice Daily and Formoterol-DPI 12µg Twice Daily, in Patients With Stable Chronic Obstructive Pulmonary Disease

The purpose of this study is to demonstrate the clinical equivalence of formoterol-HFA pMDI 12µg/actuation administered twice daily to formoterol DPI 12µg/capsule delivered by the Aerolizer inhaler and administered twice daily in patients with COPD.

Phase III, multicenter, multinational, double-blind, double-dummy, randomised, 2-arm parallel-group, 3-month study in patients with stable COPD.

Comparison in terms of efficacy and safety of the two formulations of formoterol administered as 24µg/day in a bid regimen

Inclusion Criteria:

• Male and female patients who gave written informed consent.
• Diagnosis of stable COPD according to the recommendations of the -Diagnosis of stable COPD according to the recommendations of the National Heart Lung and Blood Institute (NHLBI) Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, Edition 2003
• Age 40 years or older. Male and female patients who gave written informed consent
• History of a progressive nature of symptoms and a complaint of dyspnoea at least on exertion.
• Current or previous smoker [in both cases with a cumulative exposure to cigarette smoke of more than 20 pack-years
• Pre-bronchodilator baseline 40% > FEV1 < 70% of the predicted normal value
• Absolute value FEV1 > 0.9 L.
• FEV1/FVC < 70% (ERS criteria for predicted normal value).
• FEV1 reversibility test 30 minutes following inhalation of 400 μg of salbutamol pMDI
• A cooperative attitude and ability to be trained to use correctly the pMDI and the Aerolizer® inhaler

Exclusion Criteria:

• Female subjects: pregnant, lactating mother or lack of efficient contraception in a subject with childbearing potential (e.g. contraceptive methods other than oral contraceptives, IUD, tubal ligature).
• Current or past diagnosis of asthma.
• History of allergic rhinitis or other atopic disease (e.g. eczema).
• Largely reversible airflow obstruction.
• Onset of obstructive symptoms early in life (i.e. childhood).
• Variability of symptoms from day to day and frequent symptoms at night and early morning.
• A total blood eosinophil count higher than 500/μL.
• Significant and unstable concomitant cardiovascular, renal, hepatic, gastrointestinal,neurological, endocrine, metabolic, musculo-skeletal, neoplastic, respiratory or other clinically significant disease
• Clinical significant laboratory abnormalities indicating a significant or unstable concomitant disease.
• QTc interval (Bazett formula) higher than 460 msec
• Total 24 hours respiratory symptom score (day-time and night-time) > 2 on at least 4 consecutive days
• Lower respiratory tract infection within one month before screening visit
• Hospitalisation or emergency room treatment for an acute COPD exacerbation in the month before screening visit
• Long-term oxygen therapy.
• Patients treated with oral or injectable corticosteroids and antibiotics for a COPD exacerbation and/or a lower respiratory tract infection in the month preceding the screening visit and during the run-in period of the study.
• Patients treated with depot corticosteroids in the three months preceding the screening visit and during the 14-week study period.
• Changes in dose, schedule, formulation or product of an inhaled or nasal corticosteroid and oral modified-release theophylline within one month of screening visit and during the 14 week study period
• Patients treated with inhaled long-acting β2-agonists during the 14-week study period.
• Short-acting β2-agonists on regular use during the 14-week study period 8 hours preceding the screening visit
• Short-acting anticholinergic medications during the 14-week study period
• Long-acting anticholinergic medications (e.g. tiotropium) during the 14-week study period.
• Inhaled fixed combinations of a short-acting β2-agonist and a short-acting anticholinergic medication (e.g. Combivent) during the 14-week study period
• Inhaled fixed combinations of an inhaled corticosteroid and a long-acting β2-agonist (e.g.Seretide, Symbicort) during the 14-week study period.
• Long-acting antihistamines (e.g. Astemizole, Terfenadine) in the three months preceding the screening visit and during the 14-week study period.
• Tricyclic antidepressants, monoamine oxidase inhibitors (MAOI) and other drugs known to prolong the QTc interval during the 14-week study period.
• β-blockers in the week preceding the screening visit and during the 14-week study period.
• Intolerance to inhaled β2-adrenergic agents.
• History of intolerance or allergic reactions to any of the pMDI and DPI excipients.
• Patients who had evidence of alcohol or substance abuse, not compliant with the study protocol or not compliant with the study treatments.
• Participation in another clinical trial with an investigational drug in the four weeks preceding the screening visit