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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E.1.1.1 | Medical condition in easily understood language |
COPD is a chronic condition of the lungs which causes people to suffer symptoms such as shortness of breath and coughing. |
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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 |
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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 the non-inferiority of QVA149 110/50 μg qd compared to placebo in terms of overall SAE rate from initiation of study treatment through 30 days post last treatment. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate QVA149 110/50 μg qd compared to placebo in terms of a composite endpoint of all-cause mortality, and serious CCV events.
2. To evaluate the relative effect of treatment QVA149 compared to placebo and tiotropium on safety and tolerability during 52 weeks of treatment.
3. To compare the bronchodilator effect of QVA149 with tiotropium and placebo based on the mean pre-dose FEV1 at week 52.
4. To assess changes in health status as measured by the St. George’s Respiratory Questionnaire for COPD patients (SGRQ-C) after 52 weeks of treatment with QVA149 compared with tiotropium and placebo.
5. To compare the effect of QVA149 with tiotropium and placebo on patient reported symptoms during the treatment period.
6. To compare the bronchodilator effect of QVA149 with tiotropium and placebo based on FVC and FEV1 measurements at all post-baseline time points.
7. To compare the effect of QVA149 with placebo on time to premature discontinuation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female adults aged ≥40 yrs
• Smoking history of at least 10 pack years
• Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (moderate to severe airflow limitation as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
Guidelines, 2011)
• Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)< 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) <70%
• Modified Medical Research Council questionnaire grade of 2 or higher
Other protocol defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
• Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1
• Patients with concomitant pulmonary disease
• Patients with a history of asthma
• Any patient with lung cancer or a history of lung cancer
• Patients with a history of certain cardiovascular co-morbid conditions
• Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
• Patients in the active phase of a supervised pulmonary rehabilitation program
• Patients contraindicated for inhaled anticholinergic agents and β2 agonists
Other protocol defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall serious adverse event rate |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Electrocardiogram
2. Health Status as measured by St. George's Respirator Questionnaire for COPD patients (SGRQ-C) for COPD patients
3. Impairment of health status daily, morning and evening symptom scores
4. Percentage of nights with ‘no nighttime awakenings'
5. Percentage of days with ‘no daytime symptoms’
6. Percentage of ‘days able to perform usual daily activities’
7. Pre-Dose forced expiratory volume over in second (FEV1)
8. Pre-Dose forced vital capacity (FVC)
9. Post dose forced expiratory volume in one second (FEV1)
10. Post Dose forced vital capacity (FVC)
11. Time to discontinuation
12. Radial Pulse Rate
13. Lab values
14. Composite endpoint of all-cause mortality and serious cerebrocardiovascular events
15. Blood Pressure
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. weeks 1, 26 and 52
2. 52 weeks
3. 52 weeks
4. 52 weeks
5. 52 weeks
6. 52 weeks
7. Weeks 3, 6, 12, 26, 39 and 52
8. Weeks 3, 6, 12, 26, 39 and 52
9. Weeks 3, 6, 12, 26, 39 and 52
10. Weeks 3, 6, 12, 26, 39 and 52
11. 52 weeks
12. Weeks 3, 6, 12, 26, 39 and 52
13. Weeks 3, 6, 12, 26, 39 and 52
14. 56 weeks
15. Weeks 3, 6, 12, 26, 39 and 52
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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 | No |
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 | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 |
Argentina |
Colombia |
Croatia |
Dominican Republic |
Estonia |
Guatemala |
Hungary |
India |
Ireland |
Israel |
Korea, Republic of |
Latvia |
Lithuania |
Mexico |
Panama |
Poland |
Russian Federation |
Serbia |
Slovenia |
Turkey |
United Kingdom |
Venezuela, Bolivarian Republic of |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 4 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 4 |