Pharmacokinetics of CHF 5993 pMDI With and Without Spacer in COPD Patients

Study Overview
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Brief Summary
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The study is performed to investigate the effect of the spacing device on the pharmacokinetics of CHF 5993 pMDI active ingredients administered with and without Aerochamber Plus Flow-vu antistatic VHC spacer as a single administration in COPD patients. Moreover, the general safety and tolerability of the treatments will be evaluated.

Official Title
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Open-label, Randomized, 3-way Cross-over, Placebo Controlled, Single Dose Clinical Pharmacology Study in COPD Patients After Inhalation of CHF 5993 pMDI Using the Standard Actuator With or Without AeroChamber Plus Flow-Vu VHC Spacer

Conditions
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COPD

Intervention / Treatment
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* Drug: Beclometasone/formoterol/glycopyrrolate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD patients smokers or ex-smokers post-bronchodilator FEV1 between 30 and 60% of predicted value Exclusion Criteria: Positive serology to HIV and hepatitis Known respiratory disorder other than COPD Recent COPD exacerbations or hospitalization for COPD Treatment with non-permitted concomitant medication clinically relevant concomitant disease clinically relevant abnormal laboratory or ECG parameters

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF5993 pMDI + Spacer<br>CHF 5993 pMDI (Beclometasone/formoterol/glycopyrrolate 100/6/25 mcg per actuation) x 4 inhalations administered using Aerochamber Plus Flow-vu VHC spacer | Drug: Beclometasone/formoterol/glycopyrrolate<br> <br> * Other names: CHF5993 pMDI;|
| Active Comparator: CHF5993 pMDI<br>CHF 5993 pMDI (Beclometasone/formoterol/glycopyrrolate 100/6/25 mcg per actuation) x 4 inhalations administered using standard actuator only | Drug: Beclometasone/formoterol/glycopyrrolate<br> <br> * Other names: CHF5993 pMDI;|
| Placebo Comparator: Placebo pMDI<br>Placebo pMDI x 4 inhalations | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of B17MP, formoterol and glycopyrrolate | AUCt (up to the last quantifiable concentration) and Cmax (maximum concentration) from plasma concentrations vs time profiles. over 24h for formoterol and B17MP, over 48h for glycopyrrolate | Over 24 and 48h after single administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other pharmacokinetic parameters for formoterol, glycopyrrolate and B17MP in plasma | B17MP AUC0-30min, AUC0-24h, AUCinf, tmax, half-life Formoterol AUC0-30min, AUC0-24h, AUCinf, tmax, half-life Glycopyrrolate AUC0-30min, AUC0-48h, AUCinf, tmax, half-life | over 24 or 48h after single administration | 
| Adverse events | from the signature of the informed consent until the follow-up phone call | over a period of 6 to 11 weeks | 
| Lung function | FEV1 | 30 min after single administration | 
| plasma cortisol | cortisol AUC0-24h, Cmin and tmin | over 24 h after single administration | 
| cortisol urinary excretion | cortisol excretion corrected and not corrected for creatinine | over 24 h after single administration | 
| potassium plasma profile | potassium AUC0-24h, tmin and Cmin | over 24 h after single administration | 
| Vital signs | systolic and diastolic blood pressure | over 24 h after single administration | 
| ECG parameters | extracted from holter recording HR, QTcF, PR and QRS | over 24 h after single administration |