Safety and Efficacy Study of Glyco pMDI After Single and Repeated Administration

The study is divided into two parts:

• Part 1 will be conducted according to a single-centre, randomized, double-blind, placebo-controlled, single-dose escalation, alternating crossover design in two groups of COPD patients.

Treatments to be administered on Part 1 (SD1, SD2, SD3, SD4, SD5, SP). The primary objective of Part 1 is the evaluation of the safety and tolerability of Glyco after single administration.

• Part 2 will be conducted according to a single-centre, randomized, double-blind, placebo-controlled, 4-period, 4-treatment, repeated dose cross-over design followed by an open-label extension period with tiotropium.

Treatments administered on Part 2 (MD1, MD2, MD3, MP, Tiotropium). On the last treatment day in the morning, Formoterol 12 µg will be administered to all patients on top of placebo or Glyco or Tiotropium.

The primary objective of Part 2 is the evaluation of the efficacy of Glyco after repeated administration.

Part 2 will start after a safety review of the results obtained from Part 1.

Inclusion criteria

• Males and females patients aged 40-75 years;
• Written informed consent obtained;
• Diagnosis of moderate-severe COPD, according to the GOLD guidelines;
• Current or ex-smokers with a smoking history of ≥ 10 pack-years
• Post bronchodilator FEV1 between 40% and 80% predicted values (40% ≤ FEV1 < 80%), documented at screening visit ;
• Post bronchodilator FEV1/Forced Vital Capacity (FEV1/FVC) ≤ 0.70 (absolute value) documented at screening visit;
• Airway reversibility of at least 100 mL within 30 to 45 minutes after inhalation of ipratropium 80µg.

Exclusion criteria

• History of chronic or seasonal allergy
• Blood eosinophil count above 600 per µl
• Clinically relevant findings on physical examination laboratory and ECG parameters at screening
• Occurrence of clinically relevant abnormalities in the 24-h Holter ECG recording at screening;
• Significant disease not related to COPD (eg. Myocardial infarction, stroke within the preceding 6 months);
• Respiratory tract infection (including upper tract) 4 weeks prior to study entry requiring changing treatment;
• Patients requiring oxygen therapy on a daily basis for chronic hypoxemia;
• History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which is considered to be clinically significant by the investigator.
• Intolerance/hypersensitivity or any contra-indication to treatment with M3 Antagonist or any of the excipients contained in the formulations used in the study.
• History of alcohol or substance abuse that in the opinion of the Investigator may be of clinical significance.
• Patients treated with slow-release oral or parental corticosteroids 8 weeks prior to Screening Visit.
• Patients treated with tiotropium in the 10 days prior to the Screening Visit;
• Pregnant or lactating women and female or male subjects not willing to use an acceptable method of contraception.