Efficacy and Safety of Two Fixed Dose Combinations of Aclidinium Bromide With Formoterol Fumarate

Study Overview
=================
Brief Summary
-----------------
The purpose of this multicenter, dose-ranging study is to compare two Fixed-Dose Combinations of aclidinium bromide and formoterol fumarate with placebo, aclidinium bromide and formoterol fumarate, all administered BID in patients with stable, moderate to severe COPD. Every treatment period is 14-days long and there is a 7-days wash-out period in between them. The trial starts with a run in phase of 10 to 17-days duration and it ends up with a follow up contact 14-days after last treatment dose.

Official Title
-----------------
Efficacy, Safety and Tolerability of Two Fixed-Dose Combinations of Aclidinium Bromide With Two Doses of Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo All Administered Twice Daily in Stable, Moderate to Severe Chronic Obstructive Pulmonary Disease Patients.

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Aclidinium 200 μg / formoterol 12 μg
* Drug: Placebo
* Drug: Formoterol 12 μg
* Drug: Aclidinium 200 μg
* Drug: Aclidinium 200 μg / Formoterol 6 μg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult male or non-pregnant, non-lactating female aged between 40 and 80 years old, both inclusive. Patient with a clinical diagnosis of stable moderate to severe COPD according to the GOLD classification Current, or ex-cigarette smoker with a smoking history of at least 10 pack-years. Patient whose FEV1 at the Screening Visit measured between 10-15 minutes post inhalation of 400 mcg of salbutamol is 30% FEV1 <80% of the predicted normal value (i.e., 100 x Post-salbutamol < FEV1/ Predicted FEV1 must be < 80% and ≥ 30%). Patient whose FEV1/FVC at the Screening Visit measured between 10-15 minutes post inhalation of 400 mcg of salbutamol is < 70% (i.e., 100 x Post-salbutamol FEV1 /FVC < 70%). Patient who is eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained. Patient whose COPD symptoms and FEV1 values at the time of randomisation are stable compared to the Screening Visit, according to the investigator's medical judgment Exclusion Criteria: History or current diagnosis of asthma or exercise-induced bronchospasm. Clinically significant respiratory conditions at the time of Inform Consent signature Hospitalisation due to COPD exacerbation within the previous 3 months. Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract) within the previous 6 weeks. Patient who has a resting systolic blood pressure ≥ 200 mmHg, a resting diastolic blood pressure ≥ 120 mmHg or a resting heart rate ≥ 105 bpm at screening visit. Clinically significant cardiovascular conditions Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction. Presence of narrow-angle glaucoma. QTc [calculated according to Bazett's formulae (QTc=QT/RR1/2) above 470 milliseconds in the ECG performed at Screening Visit, Patient who does not maintain regular day/night, waking/sleeping cycles

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Formoterol 12 μg<br>Formoterol fumarate 12 μg twice daily | Drug: Formoterol 12 μg<br>* Formoterol fumarate 12 μg twice daily<br>|
| Placebo Comparator: Placebo<br>Placebo twice daily | Drug: Placebo<br>* Placebo control twice daily<br>|
| Experimental: Aclidinium 200 μg / formoterol 12 μg<br>Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) twice daily | Drug: Aclidinium 200 μg / formoterol 12 μg<br>* Aclidinium bromide 200 μg + formoterol fumarate 12 μg fixed dose combination (FDC) twice daily<br>|
| Experimental: Aclidinium 200 μg / formoterol 6 μg<br>Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) twice daily | Drug: Aclidinium 200 μg / Formoterol 6 μg<br>* Aclidinium bromide 200 μg + formoterol fumarate 6 μg fixed dose combination (FDC) twice daily<br>|
| Experimental: Aclidinium 200 μg<br>Aclidinium bromide 200 μg twice daily | Drug: Aclidinium 200 μg<br>* Aclidinium bromide 200 μg twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Normalized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) After Morning Study Drug Administration at Day 14 | FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose | 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Morning Pre-dose FEV1 at Day 14 | FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes | Day 14 | 
| Change From Baseline in Morning Peak FEV1 at Day 14 | FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose | 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bronchitis, Chronic, Emphysema