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: Moderate to severe chronic obstructive pulmonary disease (COPD); MedDRA version: 12.1Level: LLTClassification code 10009033Term: Chronic obstructive pulmonary disease

• Registration Number: EUCTR2009-017380-42-BE
• Lead Sponsor: ALMIRALL, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-02-16
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

1. Males and non-pregnant, non-lactating females aged = 40.
2. Patients with a clinical diagnosis of stable moderate to severe COPD, according to the 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%).
3. Patients whose FEV1 at Screening Visit measured between 10-15 min post inhalation of 400 µg of salbutamol is = 30% <80% of the predicted normal value (i.e., 100xobserved post-salbutamol FEV1/ predicted FEV1 <80%).
Predicted normal values to be used for calculation purposes are to be based on European Community for Steel and Coal predicted values (Quanjer et al. 1993).
4. Current or former cigarette smokers with a smoking history of at least 10 packs-year. Pack-years are calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person has smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years would have a 20 pack-year smoking history (40 cigarettes per day ÷ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history). Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion as well.
5. 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. Women of childbearing potential must have a negative pregnancy test at Screening (Visit 1) and be using at least two months before the screening visit, at least one medically approved and highly effective method of birth control defined as those which result in a low failure rate (i.e less than 1% per year) when used consistently and correctly such as implants, injectables, oral contraceptives combined with at least one barrier method, hormonal IUDs, sexual abstinence or vasectomy of the partner.
6. Patients who understand the study procedures and are willing to participate in the study as indicated by signing the informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. History or current diagnosis of asthma.
2. Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the six weeks before Screening Visit. Patients who develop a respiratory tract infection or exacerbation during the run-in period will be discontinued from the trial before randomisation.
3. Patients who have been hospitalised for an acute COPD exacerbation within 3 months prior to Screening Visit.
4. Clinically significant respiratory conditions defined as:
•Known active tuberculosis.
•History of interstitial lung or pulmonary thromboembolic disease.
•Pulmonary resection or lung volume reduction surgery during the past 12 months.
•History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener’s syndrome, etc).
•Post organ transplantation.
• Patients who in the investigator’s opinion may need pulmonary rehabilitation or thoracotomy or other lung surgery during the trial.
•Patients with a history of a1-antitrypsin deficiency.
5. Use of long-term oxygen therapy (=15hours/day).
6. Patients with a Body Mass Index (BMI) =40kg/m2.
7. Patients planned to participate in a pulmonary rehabilitation program during the trial or started within 6 weeks prior to Screening Visit (Patients on a stable pulmonary rehabilitation program more that 6 weeks prior to Screening visit and anticipated to be stable throughout the study can be enrolled).
8. Clinically significant cardiovascular conditions defined as:
•Myocardial infarction during the previous 6 months.
•Unstable angina, unstable arrhythmia which has required changes in the pharmacological therapy or other intervention (e.g. use of an automated implantable cardioverterdefibrillator) during the last 12 months, or newly diagnosed arrhythmia within the previous 3 months.
•Hospitalisation within the previous 12 months for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms at rest) according to the New York Heart Association.
9. Patients with non-controlled history of infection with HIV and/or active hepatitis.
10. QTc [calculated according to Bazett’s formulae (QTc=QT/RR1/2)] above 470 milliseconds in the manual ECG reading performed at Screening Visit.
11. Patients with clinically relevant abnormalities in the results of the clinical laboratory tests, in ECG parameters other than QTc, or in the physical examination at the screening evaluation (Visit 1), if the abnormality defines a disease state listed as an exclusion criteria, except for those related to COPD.
12. Patients with a history (within the previous 5 years) of drug and/or alcohol abuse that may prevent compliance with trial activities.
13. Patients with any other serious or uncontrolled physical or mental dysfunction that, as judged by the investigator, could place the patient at higher risk derived from his/her participation in the study, could confound the results of the study or is likely to prevent the patient from complying with the requirements of the study or completing the study.
14. Patients with a history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical bronchospasm).
15. Patients for whom the use of anticholinergic drugs is contraindicated:
•Patients with acute urina

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of three doses of aclidinium bromide (100 µg, 200 µg or 400 µg) BID compared to formoterol 12 µg BID and placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).;Secondary Objective: To evaluate the safety and tolerability of aclidinium bromide (100 µg, 200 µg or 400 µg) BID in the same target population.;Primary end point(s): Change from baseline in normalised FEV1 area under the curve over the 12-h period immediately after morning IMP administration, AUC0-12 at Day 7 on treatment.