Efficacy and Safety of Three Doses of Aclidinium Bromide Compared to Placebo and to an Active Comparator in Chronic Obstructive Pulmonary Disease (COPD) Patients.

Study Overview
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Brief Summary
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The present trial is conducted to further assess the efficacy by means of serial spirometry, safety and tolerability of three doses of aclidinium bromide administered twice a day compared to previously approved BID drug, formoterol 12 µg, and placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).after 7 days on treatment. Every treatment period is 7-days long and there is a 5 to 7-days wash-out period in between them. The trial starts with a run in phase of 11 to 17-days duration and it ends up with a follow up contact 14-days after last treatment dose.

Official Title
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Efficacy and Safety of Three Doses of Aclidinium Bromide Compared to Placebo and to an Active Comparator All Administered Twice Daily by Inhalation in Patients With Stable Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD).

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Aclidinium bromide 100 μg bid
* Drug: Aclidinium bromide 200 μg bid
* Drug: Aclidininum bromide 400 μg bid
* Drug: Placebo
* Drug: Formoterol 12 μg bid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant, non-lactating females aged ≥ 40. Patients with a clinical diagnosis of stable moderate to severe COPD, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines: (http://www.goldcopd.com) and stable airway obstruction. Post-salbutamol FEV1/FVC < 70% at Screening Visit (Visit 1) (i.e., 100xpost-salbutamol FEV1/FVC <70%). 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 salbutamol is 30% < FEV1 <80% of the predicted normal value (i.e., 100 x Post-salbutamol FEV1/ Predicted FEV1 must be < 80% and ≥ 30%). Female patients at least 1 year post-menopausal, surgically sterile (defined as having a hysterectomy or tubal ligation), or practicing a medically approved and highly effective method of contraception. Patients who understand the study procedures and are willing to participate in the study as indicated by signing the informed consent. Exclusion Criteria: History or current diagnosis of asthma. Clinically significant respiratory conditions other than COPD 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. Clinically significant cardiovascular conditions Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction. Presence of narrow-angle glaucoma. QTcB) 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
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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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aclidinium bromide 100 μg bid<br>Aclidininum bromide 100 μg twice daily by inhalation | Drug: Aclidinium bromide 100 μg bid<br>* Aclidinium bromide 100 μg twice-daily via inhalation by Eklira Genuair® inhaler: 1 puff in the morning and evening for 7 days<br>|
| Experimental: Aclidininum bromide 200 μg bid<br>Aclidininum bromide 200 μg twice daily by inhalation | Drug: Aclidinium bromide 200 μg bid<br>* Aclidinium bromide 200 μg twice-daily via inhalation by Eklira Genuair® inhaler: 1 puff in the morning and evening for 7 days<br>|
| Experimental: Aclidininum bromide 400 μg bid<br>Aclidininum bromide 400 μg twice daily by inhalation | Drug: Aclidininum bromide 400 μg bid<br>* Aclidinium bromide 400 μg twice-daily via inhalation by Eklira Genuair® inhaler: 1 puff in the morning and evening for 7 days<br>|
| Placebo Comparator: Placebo<br>Placebo twice-daily by inhalation | Drug: Placebo<br>* Placebo via inhalation in the morning and evening for 7 days<br>|
| Active Comparator: Formoterol 12 μg bid<br>Formoterol 12 μg twice daily by inhalation | Drug: Formoterol 12 μg bid<br>* Formoterol 12 μg twice-daily via inhalation by Aerolizer® dry powder inhaler: 1 puff in the morning and evening for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-12h at Day 7 on Treatment |  | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 12-24h at Day 7 on Treatment |  | Day 7 | 
| Change From Baseline in Forced Expiratory Volume in First Second (FEV1) Area Under Curve (AUC) 0-24h at Day 7 on Treatment |  | Day 7 | 
| Change From Baseline in Morning Pre-dose Forced Expiratory Volume in First Second (FEV1) at Day 7 on Treatment |  | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD