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 | 15.0 |
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 |
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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 evaluate the safety and tolerability of QVA149 27.5/12.5 μg b.i.d. and QVA149 27.5/25 μg b.i.d. in terms of adverse event reporting rate in patients with Chronic Obstructive Pulmonary Disease (COPD) with moderate to severe airflow limitation during 52 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of QVA149 27.5/12.5 μg b.i.d., QVA149 27.5/25 μg b.i.d. with QAB149 75μg q.d. over 52 weeks in terms of vital signs, ECG, and laboratory evaluations.
To evaluate the effect of QVA149 27.5/12.5 μg b.i.d., QVA149 27.5/25 μg b.i.d., with QAB149 75μg q.d. in terms of time to discontinuation.
To evaluate the bronchodilator effect of QVA149 27.5/12.5 μg b.i.d., QVA149 27.5/25 μg b.i.d, with QAB149 75μg q.d.
• in terms of mean FEV1 at 15 and 45 minutes pre-dose at week 52.
• based on FEV1 and FVC measurements at all post-baseline time points.
To evaluate the effect of QVA149 27.5/12.5 μg b.i.d., QVA149 27.5/25 μg b.i.d., with QAB149 75μg q.d.
• on time to first exacerbation.
• on symptoms reported over the 52 week treatment period.
• on daily number of puffs of rescue medication over the 52 week treatment period. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female patients with COPD according to GOLD 2011 who have signed informed consent.
2. Patients with airflow limitation of 30-80% post-bronchodilator FEV1 at run-in.
3. Current or ex-smokers with a smoking history of at least 10 packs years.
4. Patients with a mMRC score of at least 2 at run-in.
Other protocol defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
1. Patients contraindicated for muscarinic antagonist agents and beta-2 agonists.
2. Patients with a history of malignancy of any organ system, treated or untreated, within the last five years.
3. Patients with narrow-angle glaucoma, BPH or bladder-neck obstruction or moderate-severe renal impairment or urinary retention.
4. Patients who had a COPD exacerbation within 6 weeks prior to screening.
5. Patients who have a respiratory tract infection within 4 weeks prior to screening.
6. Patients requiring long term oxygen therapy prescribed for more than 12 hr per day.
7. Patients with a history of asthma.
8. Patients with an onset of respiratory symptoms, including COPD diagnosis, prior to age 40 years.
9. Patients with a blood eosinophil count of greater than 600 mm/3 during run-in.
10. Patients with concomittant pulmonary disease.
11. Patients with a history of certain cardiovascular co-morbid conditions
12. Patients with a diagnosis of alpha-1 anti-trypsin deficiency.
13. Patients with active pulmonary tuberculosis.
14. Patients in the active phase of a pulmonary rehabilitation programme.
Other protocol defined inclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall adverse event reporting rate : The overall rate of adverse events reported from initiation through 30 days post last dose |
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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. Vital signs, ECG and laboratory evaluations
2. Time to discontinuation
3. FEV1 pre-dose
4. FEV1 and FVC at all post-baseline time points
5. Time to first exacerbation
6. Symptoms reported over the 52 week period
7. Number of puffs of rescue medication over the 52 week period
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timeframe :
1.2.3.4.5.6.7. : 52 weeks |
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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 | No |
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 | No |
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
| 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 |
Bulgaria |
Finland |
Hungary |
India |
Romania |
Spain |
United States |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 25 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 25 |