E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe chronic obstructive pulmonary disease (COPD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of aclidinium bromide (100 μg, 200 μg or 400 μg) BID in the same target population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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 urinary retention, symptomatic prostatic hypertrophy, bladder neck obstruction. or narrow-angle glaucoma. (Note: Patients with well-controlled, stable, asymptomatic benign prostatic hypertrophy are not excluded). •Patients with narrow-angle glaucoma. 16. Patients unable to properly use a multidose dry powder inhaler or a pressurized metereddose inhaler (pMDI) or to perform spirometry measurements. 17. Patients who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required washout period for a particular prohibited medication. 18. Malignancy for which the patient had undergone resection, radiation therapy, or chemotherapy within the last 5 years. Patients with treated basal cell carcinoma are allowed. 19. Treatment with any IMP within 30 days (or 6 half-lives, whichever is longer) before Screening Visit. 20. Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers). 21. Patients who are unlikely to be cooperative. 22. Patients who are employees or relatives of employees at the investigative site, Almirall or Forest Laboratories. 23. Patients unable to give their consent, or patients of consenting age but under guardianship, or vulnerable patients 24. Any other conditions that, in the investigator’s opinion, might indicate the patient to be unsuitable for the study |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
5 x 5 latin square cross-over |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |