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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and the efficacy of Glycopyrrolate as pMDI after single and repeated administration.

Detailed Description
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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.

Official Title
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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.

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Glycopyrrolate
* Drug: Tiotropium
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glyco SD1<br>Single administration of Glyco pMDI dose level 1 | Drug: Glycopyrrolate<br>* pressurized metered dose inhaler<br>* Other names: CHF 5259;|
| Experimental: Glyco SD2<br>Single administration of Glyco pMDI dose level 2 | Drug: Glycopyrrolate<br>* pressurized metered dose inhaler<br>* Other names: CHF 5259;|
| Experimental: Glyco SD3<br>Single administration of Glyco pMDI dose level 3 | Drug: Glycopyrrolate<br>* pressurized metered dose inhaler<br>* Other names: CHF 5259;|
| Experimental: Glyco SD4<br>Single administration of Glyco pMDI dose level 4 | Drug: Glycopyrrolate<br>* pressurized metered dose inhaler<br>* Other names: CHF 5259;|
| Experimental: Glyco SD5<br>Single administration of Glyco pMDI dose level 5 | Drug: Glycopyrrolate<br>* pressurized metered dose inhaler<br>* Other names: CHF 5259;|
| Placebo Comparator: Placebo SP<br>Single administration of Placebo pMDI | Drug: placebo<br>* pressurized metered dose inhaler<br>|
| Experimental: Glyco MD1<br>Multiple administration of Glyco pMDI dose level 1 | Drug: Glycopyrrolate<br>* pressurized metered dose inhaler<br>* Other names: CHF 5259;|
| Experimental: Glyco MD2<br>Multiple administration of Glyco pMDI dose level 2 | Drug: Glycopyrrolate<br>* pressurized metered dose inhaler<br>* Other names: CHF 5259;|
| Experimental: Glyco MD3<br>Multiple administration of Glyco pMDI dose level 3 | Drug: Glycopyrrolate<br>* pressurized metered dose inhaler<br>* Other names: CHF 5259;|
| Placebo Comparator: Placebo MP<br>Multiple administration of placebo pMDI | Drug: placebo<br>* pressurized metered dose inhaler<br>|
| Active Comparator: Tiotropium<br>Multiple administration of tiotropium | Drug: Tiotropium<br>* inhalation powder, hard capsule<br>* Other names: Spiriva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Adverse events, vital signs, ECG parameters, 24-hours ECG holter recording, clinical laboratory abnormalities. This primary outcome is for the Part 1 of the study. | Up to 24 hours after single administration | 
| Lung function (trough FEV1) | This primary variable is for the Part 2 of the study. | 12 hours post dose after repeated administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung function | for Part 1 of the study | up to 24 hours post dose | 
| Lung function (other parameters) | for Part 2 of the study | up to 12 hours after repated administration | 
| Body plethysmography | for Part 2 of the study | up tp 12 hours after repeated administration | 
| Pharmacokinetics | Pharmacokinetics in plasma and urine. For Part 2 of the study. | up to 12 hours after single and repeated administration | 
| Safety | Adverse events, Vital signs, ECG parameters, 24-hour ECG holter recording. For Part 2 of the study. | up to 12 hours after single and repeated administration |