E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease |
|
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. |
|
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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
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 QVA149 110/50 µg q.d. as compared to fluticasone/salmeterol (500µg /50µg) b.i.d. in terms of standardized FEV1 AUC0-12h following 26 weeks of treatment in patients with moderate to severe COPD. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of QVA149 110/50 µg q.d. as compared to fluticasone/salmeterol 500/50µg b.i.d. in terms of:
• Standardized FEV1 AUC0-12h following 12 weeks of treatment.
• FVC at all time points following 12 and 26 weeks of treatment.
• The focal score of the Transitional Dyspnea Index after 12 and 26 weeks of treatment (TDI version).
• The total score of the St George’s Respiratory Questionnaire (SGRQ-C) following 12 and 26 weeks of treatment as compared to baseline.
• The mean change from baseline in daily number of puffs of rescue medication following 12 and 26 weeks of treatment.
• Symptoms reported over 12 and 26 weeks of treatment using e-diary.
• Inspiratory capacity (IC) in a subset of patients at all time points following 12 and 26 weeks of treatment.
• Safety and tolerability (electrocardiograms (ECGs), laboratory tests, blood pressure, heart rate and adverse events including COPD exacerbations and oral candidiasis) over 26 weeks of treatment. |
|
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 moderate to severe stable COPD (Stage II or Stage III) according to the GOLD Guidelines 2009.
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 a post-bronchodilator FEV1 ≥40% 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. |
|
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) except under certain
circumstances (see 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:
4. Patients with a history of long QT syndrome or whose QTc measured
at Visit 2 (Day -14) (Fridericia method) is prolonged (>450 ms for males
and females) as confirmed by the central ECG assessor.
5. Patients who have a clinically significant abnormality on the Visit 2
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).
6. Patients with Type I or uncontrolled Type II diabetes.
7. Patients who have not achieved an acceptable spirometry result at
Visit 2 in accordance with ATS/ERS criteria for acceptability and
repeatability
8. Patients with 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 re-section of the prostate may be considered for the
study, as well as patients who are asymptomatic and stable on
pharmacological treatment for the condition).
9. Patients with a 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.
10. Patients who, in the judgment of the investigator, have a clinically
relevant laboratory abnormality or a clinically significant condition
11. Patients unable to use an electronic patient diary.
12. Patients who are, in the opinion of the investigator known to be
unreliable or non-compliant.
COPD specific exclusion
13. Patients requiring long term oxygen therapy 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 last year up to and including Visit 3.
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.
16. 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.
17. Patients with lung lobectomy, lung volume reduction, or lung
transplantation.
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
19. Patients with allergic rhinitis who use a H1 antagonist or intra-nasal
corticosteroids intermittently (treatment with a stable dose is
permitted).
20. Patients with eczema (atopic), known high IgE levels, or a known
positive skin prick test in the last 5 years.
21. Patients with known history and diagnosis of α-1 antitrypsin
deficiency.
22. Patients who are participating in the active phase of a supervised
pulmonary rehabilitation programme. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate the superiority of QVA149 110/50 µg q.d. as compared to fluticasone/salmeterol (500µg /50µg) b.i.d. in terms of standardized FEV1 AUC0-12h following 26 weeks of treatment in patients with moderate to severe COPD. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 26 weeks of treatements |
|
E.5.2 | Secondary end point(s) |
To evaluate the effect of QVA149 110/50 μg q.d. as compared to
fluticasone/salmeterol
500/50μg b.i.d. in terms of:
• Standardized FEV1 AUC0-12h following 12 weeks of treatment.
• FVC at all time points following 12 and 26 weeks of treatment.
• The focal score of the Transitional Dyspnea Index after 12 and 26
weeks of treatment (TDI version).
• The total score of the St George's Respiratory Questionnaire (SGRQ-C)
following 12 and 26 weeks of treatment as compared to baseline.
• The mean change from baseline in daily number of puffs of rescue
medication following 12 and 26 weeks of treatment.
• Symptoms reported over 12 and 26 weeks of treatment using e-diary.
• Inspiratory capacity (IC) in a subset of patients at all time points
following 12 and 26 weeks of treatment.
• Safety and tolerability (electrocardiograms (ECGs), laboratory tests,
blood pressure, heart rate and adverse events including COPD exacerbations and oral candidiasis) over 26 weeks of treatment. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints are specified directly in the secondary endpoints's
description above (section E.5.2) |
|
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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 | 2 |
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 | 46 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 97 |
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 |
Belgium |
Czech Republic |
Estonia |
Germany |
Hungary |
Korea, Republic of |
Lithuania |
Norway |
Spain |
|
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |