Study to Assess Efficacy and Safety of Aclidinium Bromide and Aclidinium Bromide/Formoterol Fumarate in Stabile COPD Patients

Study Overview
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Brief Summary
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This is a multiple dose, randomised, parallel, double blind, double dummy, multicentre and multinational Phase III study to determine the efficacy and safety of Aclidinium bromide/Formoterol fumarate compared with individual components and placebo and Aclidinium bromide compared with Placebo when administered to patients with stable Chronic Obstructive Pulmonary Disease (COPD).

Official Title
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A 24-week Treatment, Randomised, Parallel-group, Double Blinded, Double-Dummy, Multicenter Study to Assess the Efficacy and Safety of Aclidinium Bromide/Formoterol Fumarate Compared With Individual Components and Placebo and Aclidinium Bromide Compared With Placebo When Administered to Patients With Stable Chronic Obstructive Pulmonary Disease.

Conditions
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COPD

Intervention / Treatment
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* Drug: Aclidinium bromide/formoterol Fixed-Dose Combination
* Drug: Aclidinium bromide
* Drug: Formoterol Fumarate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Adult male or non-pregnant, non-lactating female patients aged ≥40 2. Patients with a diagnosis of COPD prior to Visit 1 (screening) 3. Patients with moderate to severe stable COPD (Stage II or Stage III) at Visit 1: post-bronchodilator FEV1 ≥30% and < 80% and post-bronchodilator FEV1/Forced vital capacity (FVC) < 70% 4. Current or former smokers with a smoking history of ≥ 10 pack-years 5. Patients able to perform repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005 criteria at Visit 1(screening) 6. Patients who understand the study procedures and are willing to participate in the study as indicated by signing the informed consent Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff) or patients employed by or relatives of the employees of the site or sponsor. 2. Previous enrolment or randomisation in the present study 3. History or current diagnosis of asthma 4. Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening or during the run-in period 5. Patients hospitalized for COPD exacerbation (an emergency room visit for longer than 24 hours will be considered a hospitalization) within 3 months prior to screening and during the run-in period 6. Clinically significant respiratory conditions other than COPD 7. Patients who in the Investigator's opinion may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to screening 8. Use of long-term oxygen therapy (≥15 hours/day) 9. Patient who does not maintain regular day/night, waking/sleeping cycles including night shift workers 10. Clinically significant cardiovascular conditions 11. Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated hypertension 12. Patients with QT corrected interval (QTc) using Fridericia formula (QTcF) (QTc=QT/ Duration in milliseconds between two R peaks of two consecutive QRS complexes (RR1/3) >470 msec as indicated in the centralised reading report assessed at Screening (Visit 1) 13. Patients with clinically significant abnormalities in the clinical laboratory tests, ECG parameters (other than QTcF) or in the physical examination at Visit 1 (screening) 14. Patients with abnormal liver function tests defined as Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), or total bilirubin ≥ 2.5 times upper limit of normal ranges at screening 15. Patient with known non-controlled history of infection with human immunodeficiency virus and/or active hepatitis 16. Patient with a history of hypersensitivity reaction to inhaled anticholinergic drugs, sympathomimetic amines, inhaled medication or any component thereof 17. Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention, or patients with symptomatic non-stable prostatic hypertrophy 18. History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer 19. Any other serious or uncontrolled physical or mental dysfunction 20. Patients with a history (within 2 years prior to Visit 1 (screening) of drug and/or alcohol abuse that may prevent study compliance based on the Investigator judgment 21. Patients unlikely to be cooperative or cannot comply with the study procedures 22. Patients treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to screening 23. Patients who intended to use any concomitant medication not permitted by this protocol or who had not undergone the required washout period for a particular prohibited medication 24. Patients unable to give consent, or patients of consenting age but under guardianship, or vulnerable patients 25. Any other conditions that, in the Investigator's opinion, might have indicated the patient to be unsuitable for the study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 130 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 1<br>Aclidinium bromide 400μg/Formoterol fumarate 12 μg | Drug: Aclidinium bromide/formoterol Fixed-Dose Combination<br>* Inhaled Aclidinium bromide/formoterol Fixed-Dose Combination, twice per day via Genuair<br>|
| Experimental: Experimental 2<br>Aclidinium bromide 400 μg | Drug: Aclidinium bromide<br>* Inhaled Aclidinium bromide 400 μg, twice per day via Genuair<br>|
| Active Comparator: Comparator<br>Formoterol fumarate 12 μg | Drug: Formoterol Fumarate<br>* Inhaled Formoterol Fumarate 12 μg, twice per day via Turbuhaler<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Inhaled dose-matched placebo, twice per day via Genuair or via Turbuhaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in 1-hour morning post-dose dose Forced expiratory volume in 1 second (FEV1) | Change from baseline in 1-hour morning post-dose dose FEV1 of Aclidinium bromide 400 μg/Formoterol fumarate 12 μg compared to Aclidinium bromide at Week 24. | Week 24 | 
| Change from baseline in morning pre-dose (trough) FEV1 | Change from baseline in morning pre-dose (trough) FEV1 of Aclidinium bromide 400 μg/Formoterol fumarate 12 μg compared to Formoterol fumarate at Week 24. | Week 24 | 
| Change from baseline in trough FEV1 | Change from baseline in trough FEV1 of Aclidinium bromide 400 μg compared to placebo at Week 24. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in peak FEV1 | Change from baseline in peak FEV1 of Aclidinium bromide 400 μg compared to placebo at week 24 | Week 24 | 
| Improvements Transition Dyspnoea Index (TDI) focal score | Improvements TDI focal score of Aclidinium bromide 400 μg/Formoterol fumarate 12 μg and Aclidinium bromide 400μg compared to placebo at week 24 | Week 24 | 
| Change from baseline in St Georges Respiratory Questionnaire (SGRQ) total score | Change from baseline in SGRQ total score of Aclidinium bromide 400 μg/Formoterol fumarate 12 μg and Aclidinium bromide 400μg compared to placebo at week 24 | Week 24 |