Pharmacokinetic, Safety and Tolerability Study of Aclidinium/Formoterol Fixed Dose Combination and Formoterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of this Phase II study is to evaluate the pharmacokinetics, safety, and tolerability of aclidinium/formoterol fixed dose combination (FDC 400/12 μg via the Almirall Inhaler and formoterol 12 μg via the Foradil® Aerolizer®, both administered twice daily for five days to patients with moderate to severe COPD.

Official Title
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A Phase 2a, Randomized, Open-Label, 2-Way Crossover Study To Determine The Pharmacokinetics, Safety, And Tolerability Of Aclidinium/Formoterol 400/12 µg Fixed Dose Combination Via Almirall Inhaler And Formoterol 12 µg Via Foradil® Aerolizer® In Patients With Moderate To Severe Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Aclidinium/formoterol 400/12μg
* Drug: Formoterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current or former cigarette smokers with a cigarette smoking history of at least 10 pack-years A diagnosis of stable moderate to severe COPD and stable airway obstruction as defined by the Global Initiative for Chronic Obstructive Lung Disease guidelines and stable airway obstruction. Exclusion Criteria: Patients who have been hospitalized for an acute COPD exacerbation within three months prior to Screening Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the six weeks before Screening Patients with any clinically significant respiratory conditions other than COPD Clinical history that suggests that the patient has asthma as opposed to COPD Chronic use of oxygen therapy ≥ 15 hours/day Patients with clinically significant cardiovascular conditions Patients with a history of hypersensitivity reaction to inhaled anticholinergics, beta-2 agonists, sympathomimetic amines, or inhaled medications

Ages Eligible for Study
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Minimum Age: 40 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aclidinium/formoterol 400/12μg FDC<br>Aclidinium/formoterol 400/12μg fixed-dose combination (FDC), one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Almirall inhaler | Drug: Aclidinium/formoterol 400/12μg<br>* Aclidinium/formoterol 400/12μg fixed dose combination (FDC), one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Almirall inhaler<br>|
| Active Comparator: Formoterol<br>Formoterol 12μg one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Foradil® Aerolizer® | Drug: Formoterol<br>* Formoterol 12 μg one inhalation twice daily (morning and evening) for 4 days, then one inhalation (morning) on Day 5 via the Foradil® Aerolizer®<br>* Other names: Foradil® Aerolizer®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval at Steady State | The standard deviation of the measure is expressed as the coefficient of variation (%) | Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose) | 
| Maximum Formoterol Plasma Drug Concentration (Cmax) at Steady State | The standard deviation of the measure is expressed as the coefficient of variation (%) | Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose) | 
| Maximum Formoterol Plasma Drug Concentration (Cmax) Following a Single Dose | The standard deviation of the measure is expressed as the coefficient of variation (%) | Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Formoterol Plasma Concentration Versus Time Curve (AUC) Over Dosing Interval Following a Single Dose | The standard deviation of the measure is expressed as the coefficient of variation (%) | Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Chronic Obstructive Pulmonary Disease, Chronic Bronchitis, Emphysema, Airflow Obstruction, Chronic, Chronic Airflow Obstruction, Chronic Obstructive Airway Disease, Chronic Obstructive Lung Disease