Efficacy Study of SYN006 HFA MDI in Asthma Patients

Three treatments will be administered in a patient:

• A. Two inhalations of Ventolin 100 mcg,
• B. One inhalation of SYN006 180/10 mcg,
• C. Two inhalations of SYN006 180/10 mcg.

Patients will be received the study treatment according to one of the six treatment sequences according to the randomization schedule:

• A-B-C,
• B-A-C,
• C-A-B,
• C-B-A,
• A-C-B,
• B-C-A.

The efficacy endpoint is

• The change in Forced Expiratory Volume in 1 second (FEV1) within 6 hours.
• The change in Peak Expiratory Flow Rate (PEFR) within 6 hours.
• The change in Force Vital Capacity (FVC) within 6 hours.

Inclusion criteria

• Male or female patient aged >= 16 years old
• History of FEV1 >=12% and 200 ml increase after inhalation of short-acting beta 2-agonist;
• Pre-bronchodilator FEV1 > 60% and < 90% of predicted normal value at enrollment;
• Ability to inhale correctly through MDI inhaler
• Written informed consent obtained.
• Diagnosis of mild to moderate persistent asthma according to GINA with a documented history of at least 6 months duration.

Mild Persistent:

• Symptoms more than once a week but less than once a day
• Nocturnal symptoms more than twice a month
• Exacerbations may affect activity and sleep
• FEV1 or PEF >= 80% predicted
• PEF or FEV1 variability < 20 - 30%

Moderate Persistent:

• Symptoms daily
• Nocturnal symptoms more than once a week
• Exacerbations may affect activity and sleep
• Daily use of inhaled short-acting beta2-agonist
• FEV1 or PEF > 60% - < 80% predicted
• PEF or FEV1 variability > 30%

Exclusion criteria

• Currently uncontrolled asthma according to GINA guideline;
• Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients;
• Inability to carry out pulmonary function testing;
• Severe asthma associated with reduced lung function;
• Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary disease (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g., active peptic ulcer), neurological or haematological autoimmune diseases;
• Abnormal ECG at enrollment;
• History of near-fatal asthma and/or admission intensive care unit because of asthma;
• History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe hypertension, or cardiac arrhythmias;
• Percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass graft (CABG) during the previous 6 months at enrollment;
• Hospitalization for asthma during the past 3 months at enrollment;
• Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 3 months at enrollment;
• Current smokers or recent (less than one year) ex-smokers, defined as smoking at least 10 pack/years;
• History of alcohol or drug abuse;
• Pregnant or lactating females or not able to exclude pregnancy during the study period;
• 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 3 months at enrollment;
• Patients who have been previously enrolled in this study.