Safety and Tolerability of Aclidinium Bromide/Formoterol Fumarate Compared With Formoterol Fumarate in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the long-term safety and tolerability of inhaled aclidinium bromide/formoterol in patients with moderate to severe, stable chronic obstructive pulmonary disease (COPD).

Official Title
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A Long-Term, Randomized, Study of the Safety and Tolerability of a Fixed-Dose Combination of Aclidinium Bromide/Formoterol Fumarate Compared With Formoterol Fumarate in Patients With Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Aclidinium Bromide/Formoterol Fumarate
* Drug: Formoterol Fumarate


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 Visit 1 Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the six weeks before Visit 1. 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 uncontrolled infection that may place the patient at risk resulting from human immunodeficiency virus (HIV), active hepatitis and/or patients with diagnosed active tuberculosis Patients with a history of hypersensitivity reaction to inhaled anticholinergics, Patients with Stage II hypertension, defined as systolic pressure of 160 and above, and/or diastolic pressure of 100 and above Current diagnosis of cancer other than basal or squamous cell skin cancer

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Inhaled aclidinium bromide 400 μg/formoterol fumarate 12 μg fixed dose combination (FDC), high dose twice per day | Drug: Aclidinium Bromide/Formoterol Fumarate<br>* Inhaled aclidinium bromide 400 μg/formoterol fumarate 12 μg, high dose twice per day<br>|
| Active Comparator: 2<br>Inhaled formoterol fumarate 12 μg, twice per day | Drug: Formoterol Fumarate<br>* Inhaled formoterol fumarate 12 μg, twice per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients to Experience at Least One Treatment-emergent Adverse Event (TEAE) | TEAEs were coded Version 16.0 of the Medical Dictionary for Regulatory Activities (MedDRA) | Up to study Week 56 ± 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients to Experience Any Potentially Clinically Significant (PCS) Post-baseline Change in Clinical Laboratory Values for Hematology, Chemistry or Urinalysis at the End of the Study | <0.85 x lower limit of normal (LLN) or > 1.15 upper limit of normal (ULN) for hemoglobin, hematocrit, red blood cell, platelet, white blood cell, neutrophil and lymphocyte counts >1.15 × ULN for eosinophil, basophil and monocyte counts >1.15 x ULN for aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, total bilirubin, creatinine kinase, lactate dehydrogenase, blood urea nitrogen, creatinine, uric acid, total cholesterol, triglycerides <0.85 x LLN or >1.15 ULN for fasting glucose, calcium, phosphorus, total protein and albumin <0.95 x LLN or >1.05 x ULN for sodium, potassium and chloride Urinary blood, ketones or pH <0.85 x LLN or > 1.15 ULN | Up to study Week 52 | 
| Percentage of Patients to Experience a Potentially Clinically Significant (PCS) Change in Pulse Rate, Systolic and Diastolic Blood Pressure | Systolic BP ≥180 mmHg and increase ≥20 mmHg from baseline or ≤90 mmHg and decrease ≥20 mmHg from baseline; Diastolic BP ≥105 mmHg and increase ≥15 mmHg from baseline or ≤50 mmHg and decrease ≥15 mmHg from baseline; Pulse rate ≥ 110 bpm and increase ≥ 15% from baseline or ≤ 50 bpm and decrease ≥15% from baseline | Up to study Week 56 ± 3 days | 
| Percentage of Patients to Experience Potentially Clinically Significant Changes in ECG From Baseline | Potentially clinically significant changes were defined as listed in the table below for QT interval, QTcB, QTcF, QRS interval, PR interval and heart rate (HR) | Up to study Week 56 ± 3 days | 

 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