| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Obstructive Pulmonary Disease (COPD) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010952 |
| E.1.2 | Term | COPD |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| 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 demonstrate the superiority of QVA 110/50 μg compared to both QAB149 150 μg and NVA237 50 μg in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post-dose) following 26 weeks of treatment in patients with moderate to severe COPD. |
|
| E.2.2 | Secondary objectives of the trial |
To demonstrate the superiority of QVA149 110/50 μg compared to placebo following 26 weeks of treatment in terms of:
• The level of breathlessness experienced by the patients evaluated using the Transitional Dyspnea Index (TDI)
• The health related quality of life as reported by the patients evaluated using the St.
George’s Respiratory Questionnaire (SGRQ)
• The rescue medication used (number of puffs) reported by the patients evaluated using the patient diary |
|
| 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 |
Exploratory pharmacogenetic analysis is included in this study with the objectives of
identifying inherited genetic factors that may:
1. be related to COPD or QVA149/QAB149/NVA237 mechanisms of action
2. predict response to treatment with QVA149, QAB149, or NVA237
3. predict predisposition to side effects
4. explain variability in drug ADME |
|
| E.3 | Principal inclusion criteria |
1. Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
2. Patients with moderate to severe stable COPD (Stage II or Stage III) according to the GOLD Guidelines 2008.
3. Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten packyears are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.)
4. Patients with a post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 at Visit 2 (Day -14). (Post refers to 1 hour after sequential inhalation of 84 μg (or equivalent dose) of ipratropium bromide and 400 μg of salbutamol)
5. Symptomatic patients, according to daily electronic diary data between Visit 2 (-14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3. (The main study Diary will be used for this.) |
|
| E.4 | Principal exclusion criteria |
1. Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).
2. Women of child-bearing potential (WOCBP) [further defined in protocol], unless specific criteria are met [defined in protocol]
3. Patients contraindicated for treatment with, or having a history of reactions/
hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any
component thereof:
• anticholinergic agents
• long and short acting beta-2 agonists
• sympathomimetic amines.
• lactose or any of the other excipients
7. Patients who have not achieved an acceptible spirometry result at Visit 2 in accordance with ATS/ERS criteria for acceptibility and repeatability.
8. Patients who have had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to Visit 1 or between Visit 1 and Visit 3.
9. Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1. 10. Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis, sarcoidosis, interstitial lung disorder or pulmonary hypertension.
12. Patients who, in the judgment of the investigator, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to):
• unstable ischemic heart disease, left ventricular failure (NYHA Class III & IV),
history of myocardial infarction, arrhythmia (excluding chronic stable AF). Patients
with such events not considered clinically significant by the investigator may be
considered for inclusion in the study.
• history of malignancy of any organ system (including lung cancer), treated or
untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
• uncontrolled hypo-or hyperthyroidism, hypokalemia or hyperadrenergic state
• narrow-angle glaucoma
• symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (Patients with a transurethral resection of prostate (TURP) are excluded from the study. Patients who have undergone full resection of the prostate may be considered for the study, as well as patients who are asymptomatic and stable on pharmacological treatment for the condition).
• any condition which might compromise patient safety or compliance, interfere with
evaluation, or preclude completion of the study
13. Patients requiring long term oxygen therapy (> 15 h a day) on a daily basis for chronic hypoxemia.
14. Patients who have had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to Visit 1 or between Visit 1 and Visit 3.
• Patients who develop a COPD exacerbation during period between Visits 1 and 3 will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.
15. Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1
. Patients who develop an upper or lower respiratory tract infection during the screening period (up to Visit 3) will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection.
18. Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count >600/mm3 (at Visit 2) or onset of symptoms prior to 40 years. Patients without asthma but who have a blood eosinophil count >600/mm3 at Visit 2 are excluded
Other exclusion criteria are defined in the protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To demonstrate the superiority of QVA 110/50 μg compared to both QAB149 150 μg and NVA237 50 μg in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post-dose) following 26 weeks of treatment in patients with moderate to severe COPD. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 194 |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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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