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

Randomized, Double-blind, Placebo-controlled, Cross-over Study to Investigate the Bronchodilator Efficacy and Safety After Single and Repeated Administrations of Different Doses of Glycopyrrolate Via pMDI in Moderate to Severe COPD Patients.

The purpose of this study is to evaluate the safety and the efficacy of Glycopyrrolate as 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.