A 26-week treatment, multi-center, randomized, double-blind, double dummy, parallel-group study to assess the efficacy, safety and tolerability of QVA149 compared to fluticasone/salmeterol in patients with moderate to severe chronic obstructive pulmonary disease

• Register: EUCTR
• Last refreshed on: 10 July 2012
• Main ID: EUCTR2010-023621-37-HU
• Date of registration: 14/01/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 26-week treatment, multi-center, randomized, double-blind, double dummy, parallel-group study to assess the efficacy, safety and tolerability of QVA149 compared to fluticasone/salmeterol in patients with moderate to severe chronic obstructive pulmonary disease
• Scientific title: A 26-week treatment, multi-center, randomized, double-blind, double dummy, parallel-group study to assess the efficacy, safety and tolerability of QVA149 compared to fluticasone/salmeterol in patients with moderate to severe chronic obstructive pulmonary disease
• Date of first enrolment: 08/03/2011
• Target sample size: 522
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023621-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium, Czech Republic, Estonia, Germany, Hungary, Lithuania, Spain

Key inclusion & exclusion criteria

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.
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 diagn

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease
MedDRA version: 12.1 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease

Intervention(s)

Product Code: QVA149
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Glycopyrronium bromide
Current Sponsor code: NVA237
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Indacaterol maleate
Current Sponsor code: QAB149
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 110-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Trade Name: Seretide Accuhaler
Product Name: Seretide Accuhaler
Pharmaceutical Form: Inhalation powder
CAS Number: 94749-08-3
Other descriptive name: SALMETEROL XINAFOATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
CAS Number: 80474-14-2
Other descriptive name: FLUTICASONE PROPIONATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: 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.

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.

Secondary Objective: 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.

Secondary ID(s)

2010-023621-37-ES

CQVA149A2313