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 | 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 safety/tolerability of 52 weeks of treatment with QVA149 (110μg indacaterol/50μg glycopyrrolate) once a day on adverse event reporting rate in patients with moderate or severe Chronic Obstructive Pulmonary Disease (COPD) |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the safety of QVA149 with placebo over 52 weeks treatment based on vital signs, ECGs, laboratory evaluations. 2. To compare the bronchodilator effect of QVA149 with placebo based on the mean FEV1 at 15 and 45 minutes pre-dose at week 52. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following 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 pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.) 4. Patients with post-bronchodilator FEV1 ≥ 30% and <80% of the predicted normal, and post-bronchodilator FEV1/FVC 0.7 at Visit 2 (Post refers to 1 hour after sequential inhalation of 84 μg (or equivalent dose) of ipratropium bromide and 400 μg of salbutamol or equivalent dose of albuterol) 5. Patients, according to daily electronic diary data between Visit 2 and Visit 3, with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3. |
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E.4 | Principal exclusion criteria |
Patients fulfilling any of the following criteria are not eligible for inclusion in this study: 1. Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test). 2. Women of child-bearing potential (WOCBP), 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 months 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 (> 15h a day) on a daily basis for chronic hypoxemia. 4. Patients who have had a COPD exacerbation that required treatment with antibiotics or oral steroids or hospitalization in the 6 weeks prior to Visit 1 or between Visit 1 and Visit 3 5. Patients who develop a COPD exacerbation during the 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 6. Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1. Patients who develop an upper or lower 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) 7. 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. 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) • 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 • 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 age 40 years. 11. Patients with eczema, known high IgE levels or known positive skin prick test. 12. Patients with allergic rhinitis who use H1 antagonists or intranasal corticosteroids intermittently (treatment with a constant dose is permitted) 13. Patients with known history and diagnosis of alpha-1 antitrypsin deficiency 14. Patients who are participating in the active phase of a supervised pulmonary rehabilitation programme 15. Patients with Type 1 or uncontrolled Type II diabetes 16. 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 17. Patients with a history of long QT syndrome or whose QTc measured at Visit 2 (Fridericia method) is prolonged (450 ms for males and females) as confirmed by the central ECG assessor 18. Patient who have a clinically significant abnormality on the screening or baseline ECG who in the judgment of the investigator would be at potential risk if enrolled into the study. These patients should not be re-screened |
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E.5 End points |
E.5.1 | Primary end point(s) |
safety/tolerability of 52 weeks of treatment with QVA149 (110μg indacaterol/50μg glycopyrrolate) |
|
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 | 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) | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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
|
End of trial is provided in the protocol. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |