E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) |
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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 | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 | 10010953 |
E.1.2 | Term | COPD exacerbation |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 demonstrate that QVA149 (110/50 μg o.d.) is superior to NVA237 (50 μg o.d.) with regard to the rate of moderate to severe COPD exacerbations during the treatment period. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that QVA149 (110/50 μg o.d.) is superior to open-label tiotropium (18 μg o.d.) with regard to the rate of moderate to severe COPD exacerbations during the treatment period.
For other secondary objectives, please consult the protocol. |
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E.2.3 | Trial contains a sub-study | No |
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 severe to very severe COPD (Stage III or IV) 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). 4. Patients with a post-bronchodilator FEV1 < 50% of the predicted normal value, and postbronchodilator FEV1/FVC < 0.70 at Visit 2 (day -14). (Post refers to 1 h after sequential inhalation of 84 μg (or equivalent dose) of ipratropium bromide and 400 μg of salbutamol). 5. A documented history of at least 1 COPD exacerbation in the previous 12 months that required treatment with systemic glucocorticosteroids and/or antibiotics. |
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E.4 | Principal exclusion criteria |
1. Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test) 2. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 mths of natural (spontaneous) amenorrhea, OR 6 weeks after surgical bilateral oophorectomy (with or without hysterectomy) OR are using one or more of the following acceptable methods of contraception: • surgical sterilization (e.g. bilateral tubal ligation)• hormonal contraception (implantable, patch, oral, IM), and copper coated IUD (if accepted by local regulatory authority and ethics committee)• double barrier method (diaphragm plus condom) • At the discretion of the investigator, total abstinence is acceptable in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance • Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. NOTE: Reliable contraception should be maintained throughout the study 3. Patients requiring long term oxygen therapy (> 15 h a day) on a daily basis for chronic hypoxemia 4. Patients who have had a COPD exacerbation that required treatment with antibiotics, oral steroids or hospitalization in the 6 weeks prior to Visit 1 or between Visit 1 (Day -21) and Visit 3 (Day 1) 5. Patients who develop a COPD exacerbation during a period between Visit 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 6. Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1 (Day -21) • Patients who develop an upper or lower respiratory tract infection during the screening period (up to Visit 3 (Day 1) will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection 7. Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), clinically significant bronchiectasis, sarcoidosis, interstitial lung disorder or pulmonary hypertension 8. Patients with lung lobectomy, or lung volume reduction or lung transplantation 9. 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, 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 TURP are excluded from the study) • any condition which might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study 10. 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 having a blood eosinophil count >600/mm3 at Visit 2 are excluded.
For additional exclusion criteria, please consult the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate that QVA149 (110/50 μg o.d.) is superior to NVA237 (50 μg o.d.) with regard to the rate of moderate to severe COPD exacerbations during the treatment period. |
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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 | No |
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 | Yes |
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 | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 164 |
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 |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |