safety and efficacy study of glyco pmdi after single and repeated administration

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Summary: 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.

Eligibility criteria:
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.