Comparison of long-term safety of the combination product QVA149A against placebo and standard of care treatment in Chronic Obstructive Pulmonary Disease patients with moderate to severe airflow limitation

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2012-002057-38-LV
• Date of registration: 22/08/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Service AG
• Public title: Comparison of long-term safety of the combination product QVA149A against placebo and standard of care treatment in Chronic Obstructive Pulmonary Disease patients with moderate to severe airflow limitation
• Scientific title: A placebo and active controlled study to assess the long-term safety of once daily QVA149 for 52 weeks in Chronic Obstructive Pulmonary Disease (COPD) patients with moderate to severe airflow limitation
• Date of first enrolment: 02/10/2012
• Target sample size: 1224
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002057-38
• 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 Number of treatment arms in the trial: 3

Countries of recruitment

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

Contacts

• Name: Pauline Roudot
• Affiliation: Novartis Pharma AG

• Name: Pauline Roudot
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

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
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 612
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 612

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 ß2 agonists

Other protocol defined exclusion criteria may apply


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

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 15.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Indacaterol maleate/Glycopyrronium bromide
Product Code: QVA149
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Current Sponsor code: NVA237
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
CAS Number: 753498-25-8
Current Sponsor code: QAB149
Other descriptive name: INDACATEROL MALEATE
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: Spiriva Handihaler
Product Name: Spiriva Handihaler
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: TIOTROPIUM BROMIDE
CAS Number: 139404-48-1
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 18-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: 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.

Secondary Objective: 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.

Primary end point(s): Overall serious adverse event rate

Timepoint(s) of evaluation of this end point: 56 weeks

Secondary Outcome(s)

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

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

Secondary ID(s)

CQVA149A2339

2012-002057-38-SI

Source(s) of Monetary Support

Novartis Pharma Service AG