| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic obstructive pulmonary disease (COPD) |
|
| E.1.1.1 | Medical condition in easily understood language |
COPD is a chronic lung disease that causes shortness of breath and coughing.
A bronchodilator helps to open your airways and makes it easier to get air in and out of the lungs. |
|
| 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 |
1. To assess the long term bronchodilator efficacy of Aclidinium bromide/Formoterol fumarate, administered twice a day, compared to Salmeterol/Fluticasone propionate (SeretideTM AccuhalerTM) in symptomatic COPD patients.
2. To compare the benefits of Aclidinium bromide/Formoterol fumarate, administered twice a day, versus twice-daily regimen of SeretideTM AccuhalerTM in disease-related health status and COPD symptoms.
3. To evaluate the long term safety and tolerability of Aclidinium bromide/Formoterol fumarate, administered twice a day, compared to twice daily SeretideTM AccuhalerTM in the same target population. |
|
| 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 |
| An additional 12-h serial spirometry sub-study to be conducted for a sub-group of 20% of patients at selected sites. |
|
| E.3 | Principal inclusion criteria |
For inclusion and randomisation in the trial, patients must meet each of the following criteria at Screening Visit (Visit 1) and at Visit 2 prior to randomisation.
1. Adult male or non-pregnant, non-lactating female aged ≥ 40. Women of childbearing potential will follow specific study requirements.
Explanatory note: 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. Women of childbearing potential are allowed to enter the trial if they show to have a negative serum pregnancy test at the Screening Visit (Visit 1) 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 intra uterine devices (IUDs), sexual abstinence or vasectomy of the partner.
2. Current or ex-cigarette smoker, with a smoking history of at least 10 pack-years.
Explanatory note: Ex-smoker definition includes those patients who quit smoking more than 6 months prior to the Screening Visit. 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). When the patient has been smoker during several periods of time separated by inactivity periods, the total pack years resulting from several periods of smoking will be added up.
Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion as well.
3. Patients with a clinical diagnosis of COPD according to GOLD guidelines 2013, with a post bronchodilator FEV1 <80%, and FEV1/FVC < 70% at Screening Visit (Visit 1).
Explanatory note: 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. 199320). (i.e., 100xpost-salbutamol FEV1/FVC <70%).
4. Symptomatic patients with a CAT≥10 at Screening and Randomisation Visit (Visit 1 and 2)
Explanatory note: CAT questionnaire cannot be repeated.
5. Patient must be able to perform repeatable pulmonary function testing for FEV1 according to ATS/ERS 2005 criteria at Screening Visit.
6. 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. |
|
| E.4 | Principal exclusion criteria |
For inclusion and randomisation in the trial, patients must NOT meet any of the following criteria at Screening Visit (Visit 1) and at Visit 2 prior to randomisation.
1. History or current diagnosis of asthma.
2. Patients who develop a respiratory tract infection or COPD exacerbation within 6 weeks (or 3 months if hospitalisation was required) before the Screening Visit (Visit 1) or during the run-in period.
3. Clinically significant respiratory conditions
Explanatory note: Clinically significant respiratory conditions, some examples are:
-Known active tuberculosis or pulmonary hypertension.
-History of interstitial lung disorder: Exposure related interstitial lung disease; isease associated interstitial lung disease; Interstitial lung disease of distinct or unknown cause/pathology.
-History of massive pulmonary thromboembolic disease.
-History of lung lobectomy, lung volume reduction or 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
4. Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated hypertension.
5. Patient who in the investigator’s opinion may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to Screening Visit.
6. Use of long-term oxygen therapy (≥ 15 hours/day).
7. Patients treated on daily basis with triple therapy (LABA+LAMA+ICS) within 4 weeks prior to the Screening Visit.
8. Patient who does not maintain regular day/night, waking/sleeping cycles including night shift workers.
Explanatory note: Patients with symptomatic sleep apnoea syndrome, any disease related with sleep disturbances such as restless-legs syndrome or somnambulism are to be excluded. However the use of continuous positive airway pressure (CPAP) is not an exclusion criteria.
9. Clinically significant cardiovascular conditions.
Explanatory note: Clinically significant cardiovascular conditions, some examples are:
-Myocardial infarction within the 6 months prior to Screening Visit (Visit 1)
-Unstable angina or unstable arrhythmia meaning which has required changes in the pharmacological therapy or other intervention within 12 months prior to Screening Visit (Visit 1), or newly diagnosed arrhythmia within the previous 3 months prior to Screening Visit (Visit 1).
-Hospitalisation within 12 months prior to Screening Visit (Visit 1) 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 NYHA.
10. Patient with clinically relevant abnormalities in the results of the clinical laboratory tests, ECG parameters or in the physical examination at the Screening Visit (Visit 1)
11. Patient with a history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical bronchospasm).
12. Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention, or patients with symptomatic non-stable prostatic hypertrophy.
Explanatory note: Patients with well-controlled, stable, asymptomatic benign prostatic hypertrophy are not excluded.
13. Patient with known non-controlled history of infection with human immunodeficiency virus (HIV) and/or active hepatitis.
14. History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer.
Explanatory note: Patients are excluded whether or not there is evidence of local recurrence or metastases
15. Patient with any other serious or uncontrolled physical or mental dysfunction.
16. Patient with a history (within 2 years prior to Screening Visit) of drug and/or alcohol abuse that may prevent study compliance based on investigator judgment.
17. Patient unlikely to be cooperative or that can’t comply with the study procedures.
18. Patient treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to Screening Visit.
19. Patient who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required stabilization periods for prohibited medication.
20. Any other conditions that, in the investigator’s opinion, might indicate the patient to be unsuitable for the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Please refer to point E.5.1 |
|
| E.5.2 | Secondary end point(s) |
| TDI focal score at week 24 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please refer to point E.5.2 |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | 2 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 139 |
| 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 |
| Bulgaria |
| Canada |
| Czech Republic |
| France |
| Germany |
| Hungary |
| Italy |
| Lithuania |
| Netherlands |
| Poland |
| South Africa |
| Spain |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 25 |
| 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 | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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