Efficacy, Safety and Tolerability of Two Fixed Dose Combinations of Aclidinium Bromide/Formoterol Fumarate, Aclidinium Bromide, Formoterol Fumarate and Placebo for 28-Weeks Treatment in Patients With Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of this Phase III study is to evaluate the long-term safety and tolerability of two fixed-dose combinations of inhaled aclidinium bromide/formoterol fumarate, aclidinium bromide, formoterol fumarate and placebo in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD). Long-term efficacy, pharmacoeconomic and health-related quality of life assessments will also be evaluated. This extension study will include a 28 week treatment period, followed by a four week follow up visit. All patients will remain in the same treatment group as for the lead-in study and continue on one of the four treatment arms or placebo.

Official Title
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A Phase III, Long-term, Randomized, Double-blind, Extension Study of the Efficacy, Safety, and Tolerability of Two Fixed Dose Combinations of Aclidinium Bromide/Formoterol Fumarate, Aclidinium Bromide, Formoterol Fumarate and Placebo for 28- Weeks Treatment 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 Fixed-Dose Combination (FDC)
* Drug: Aclidinium bromide/formoterol Fixed-Dose Combination (FDC)
* Drug: Aclidinium bromide
* Drug: Formoterol Fumarate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of the treatment phase of the lead-in study, LAC-MD-31 Written informed consent obtained from the patient before the initiation of any study specific procedures No medical contraindication as judged by the PI Compliance with LAC-MD-31 study procedures and IP dosing. Exclusion Criteria: No specific exclusion criteria

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>Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) high dose | Drug: Aclidinium bromide/formoterol Fixed-Dose Combination (FDC)<br>* Inhaled Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) high dose, twice per day<br>|
| Experimental: 2<br>Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) low dose | Drug: Aclidinium bromide/formoterol Fixed-Dose Combination (FDC)<br>* Inhaled Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) low dose, twice per day<br>|
| Active Comparator: 3<br>Aclidinium bromide 400 μg | Drug: Aclidinium bromide<br>* Inhaled Aclidinium bromide 400 μg, twice per day<br>|
| Active Comparator: 4<br>Formoterol Fumarate 12 μg | Drug: Formoterol Fumarate<br>* Inhaled Formoterol Fumarate 12 μg, twice per day<br>|
| Placebo Comparator: 5<br>Placebo | Drug: Placebo<br>* Inhaled dose-matched placebo, 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 Any Treatment-emergent Adverse Event | For each safety parameter, the last assessment made before the first dose of investigational product in the lead-in study (LAC MD-31) was used as the baseline for all analyses of that safety parameter in this extension study | Baseline of lead-in study to follow-up call 14±3 days after last dose of investigational product (up to Week 52) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis | Potentially clinically significant change: >1.15 × upper limit of normal (ULN) for absolute cell count of basophils, eosinophils or monocytes, blood alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, total cholesterol, creatine kinase, creatinine, gamma glutamyl transferase, lactate dehydrogenase, triglycerides or uric acid <0.85 x lower limit of normal (LLN) or > 1.15 ULN for hematocrit ratio, haemoglobin, lymphocytes or neutrophils absolute cell count, platelet count (thrombocytes), red or white blood cell count, calcium, fasting glucose, phosphorus, total protein, or urinary pH <0.95 x LLN or >1.05 x ULN for chloride, potassium, sodium Urinary glucose ≥0.015, blood or ketones or protein ≥1 or specific gravity >1.1 × ULN The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study | Baseline of lead-in study to end of treatment (up to Week 52) | 
| Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value |  | Baseline of lead-in study to end of treatment (up to Week 52) | 
| Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight) | Potentially clinically significant change: 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 Weight increase or decrease ≥7% from baseline The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study | Baseline of lead-in study to end of treatment (up to Week 52) | 

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