| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Obstructive Pulmonary Disorder |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic Obstructive Pulmonary Disorder |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010952 |
| E.1.2 | Term | COPD |
| E.1.2 | System Organ Class | 100000004855 |
|
| 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 long-term bronchodilation of aclidinium/formoterol fixed dose combinations compared to individual components and placebo, when administered twice daily via inhalation to COPD patients.
- To assess the benefits of aclidinium/formoterol fixed dose combinations in COPD symptoms, disease-related health status and COPD exacerbations compared to individual components and placebo, when
administered twice daily via inhalation to COPD patients.
- To evaluate the long-term safety and tolerability of aclidinium/formoterol fixed dose combinations compared to individual components and placebo when administered twice daily via inhalation to COPD patients. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
2011-04-28. Final
A subset of 20% of the total patients will have 24-hour ECG Holter recording at Screening Visit and at 12 and 24 weeks on study treatment.
In a different subset of 20% of total patients, additional spirometry assessments will be performed at Randomisation Visit and at 12 and 24 weeks on treatment. |
|
| E.3 | Principal inclusion criteria |
1. Adult male or non-pregnant, non-lactating female aged ≥40. Women of childbearing potential are
allowed to enter the trial if they show to have a negative serum pregnancy test at the Screening
Visit and are using, during the last 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.
(A female is considered to be of childbearing potential unless she has had a hysterectomy, is at
least one year post-menopausal or has undergone tubal ligation).
2. Current or ex-cigarette smoker, with a smoking history of at least 10 pack-years.
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).
3. Patient with a clinical diagnosis of stable COPD according to the GOLD Guidelines at the
Screening Visit (http://www.goldcopd.org).
4. Patient whose FEV1/FVC at the Screening Visit measured between 10-15 minutes post inhalation
of 400 μg of salbutamol is < 70% (i.e., 100 x Post-salbutamol FEV1 /FVC < 70%).
5. Patient with a diagnosis of moderate to severe COPD according to the GOLD Guidelines
classification (stages II and III) at the Screening Visit: FEV1 measured between 10-15 minutes
post inhalation of 400 μg 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%).
(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. 199324)).
6. Patient must be able to perform repeatable pulmonary function testing for FEV1 according to
ATS/ERS 2005 criteria at Screening Visit. |
|
| 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
6 weeks before Screening Visit.
3. Patient hospitalised for COPD exacerbation within 3 months prior to Screening Visit.
4. Clinically significant respiratory conditions defined as:
• Known active tuberculosis.
• History of interstitial lung or massive pulmonary thromboembolic disease.
• Pulmonary resection or lung volume reduction surgery within 12 months prior to Screening
Visit.
• History of lung transplantation.
• Patients who in the investigator’s opinion may need thoracotomy or other lung surgery during
the trial.
• History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic
fibrosis, Kartagener’s syndrome, etc).
• Known a1-antitrypsin deficiency.
6. Use of long-term oxygen therapy (≥ 15 hours/day).
7. Patient who does not maintain regular day/night, waking/sleeping cycles including night shift
workers (e.g., history of sleep apnoea syndrome, any disease related with sleep disturbances
such as restless-legs syndrome or somnambulism).
8. Clinically significant cardiovascular conditions defined as:
• Myocardial infarction within the 6 months prior to Screening Visit.
• Thoracic surgery within 12 months prior to Screening Visit.
• Unstable angina or unstable arrhythmia meaning which has required changes in the
pharmacological therapy or other intervention within 12 months prior to Screening Visit, or
newly diagnosed arrhythmia within the previous 3 months prior to Screening Visit.
• Hospitalisation within 12 months prior to Screening Visit 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) as per the New York Heart Association.
10. Patient with QTc [calculated according to Bazett formulae (QTc=QT/RR1/2) > 470 msec as
indicated in the centralised reading report assessed at Screening Visit.
11. Patient with clinically relevant abnormalities in the results of the clinical laboratory tests, ECG
parameters (other than QTc Bazzet) or in the physical examination at the Screening Visit, if the
abnormality defines a disease state listed as exclusion criteria, except for those related to COPD.
12. Patient with a history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic
amines, or inhaled medication or any component thereof (including report of paradoxical
bronchospasm). Patient with known narrow-angle glaucoma, symptomatic bladder neck
obstruction or acute urinary retention.
13. Patient with symptomatic non-stable prostatic hypertrophy. (However, patients with wellcontrolled,
stable, asymptomatic benign prostatic hypertrophy are not excluded).
20. Patient unable to properly use a dry powder (DPI) or pressured metered-dose inhaler (pMDI)
inhaler device or to perform spirometry measurements.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Co-primary efficacy variables (at Week 24 on treatment):
- Change from baseline in morning pre-dose (trough) FEV1 of each aclidinium/formoterol
FDC dose compared to formoterol monotherapy 12 μg.
- Change from baseline in 1-hour post-morning dose FEV1 of each aclidinium/formoterol FDC
dose compared to aclidinium monotherapy 400 μg. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Improvement of TDI focal score of each aclidinium/formoterol FDC dose compared to
placebo.
- Change from baseline in SGRQ total score of each aclidinium/formoterol FDC dose
compared to placebo. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 175 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Austria |
| Belgium |
| Bulgaria |
| Croatia |
| Czech Republic |
| Denmark |
| Finland |
| France |
| Germany |
| Hungary |
| Italy |
| Korea, Republic of |
| Netherlands |
| Poland |
| Romania |
| Russian Federation |
| Slovakia |
| South Africa |
| Spain |
| Sweden |
| United Kingdom |
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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