A multi-centre randomized double blind 12-week study to assess the efficacy, safety and tolerability of QVA149 in patients with COPD who have moderate to severe airflow limitation

• Register: EUCTR
• Last refreshed on: 12 May 2014
• Main ID: EUCTR2012-003347-30-HU
• Date of registration: 04/01/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multi-centre randomized double blind 12-week study to assess the efficacy, safety and tolerability of QVA149 in patients with COPD who have moderate to severe airflow limitation
• Scientific title: A 12-week treatment, multi-center, randomized, double-blind, parallel group, placebo and active controlled study to assess the efficacy, safety, and tolerability of QVA149 (indacaterol maleate /glycopyrronium bromide) in COPD patients with moderate to severe airflow limitation
• Date of first enrolment: 19/02/2013
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003347-30
• 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: 4

Countries of recruitment

Argentina, Colombia, Egypt, France, Guatemala, Hungary, Mexico, Panama, Slovakia, Slovenia, United States, Venezuela, Bolivarian Republic of

Contacts

• Name: Public Information Desk
• Affiliation: Novartis Hungária Kft., Pharma

• Name: Public Information Desk
• Affiliation: Novartis Hungária Kft., Pharma

Key inclusion & exclusion criteria

Inclusion criteria:
•Male and female patients that have signed informed consent and are >/= 40 years of age.
•Patients with stable Chronic Obstructive Pulmonary Disease (COPD) according to GOLD 2011.
•Patients with a post-bronchodilator Force Expiratory Volume in one second (FEV1) of >/= 30% and < 80% predicted and a post-bronchodilator FEV1/ Forced Vital capacity (FVC) <0.70.
•Current or ex-smokers who have a smoking history of at least 10 pack years.
•Patients with an mMRC grade 2 or greater.


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 520
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 480

Exclusion criteria:
•Patients contraindicated for muscarinic antagonist agents and beta-2 agonists.
•Patients with a history of malignancy of any organ system, treated or untreated, within the last five years.
•Patients with narrow-angle glaucoma, Benign Prostatic Hyperplasia (BPH) or bladder-neck obstruction or moderate-severe renal impairment or urinary retention.
•Patients who had a COPD exacerbation within 6 weeks prior to screening.
•Patients who have a respiratory tract infection within 4 weeks prior to screening.
•Patients requiring long term oxygen therapy prescribed for more than 12 hour per day.
•Patients with a history of asthma.
•Patients with an onset of respiratory symptoms, including COPD diagnosis, prior to age 40 years.
•Patients with a blood eosinophil count of greater than 600 mm/3 during run-in.
•Patients with concomitant pulmonary disease.
•Patients with a history of certain cardiovascular co-morbid conditions
•Patients with a diagnosis of alpha-1 anti-trypsin deficiency.
•Patients with active pulmonary tuberculosis.
•Patients in the active phase of a pulmonary rehabilitation programme.
•Other protocol-defined exclusion criteria may apply.



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

Health Condition(s) or Problem(s) studied

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

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 14.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855

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: 12.5-
INN or Proposed INN: INDACATEROL MALEATE
CAS Number: 753498-25-8
Current Sponsor code: QAB149
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 27.5-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Product Name: Indacaterol
Product Code: QAB149
Pharmaceutical Form: Inhalation powder, hard capsule
CAS Number: 753498-25-8
Current Sponsor code: QAB149
Other descriptive name: INDACATEROL MALEATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Product Name: Glycopyrronium bromide
Product Code: NVA237
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: 12.5-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): Standardized Forced Expiratory Volume in one second Area Under the Curve (AUC) following 12 weeks of treatment.

Main Objective: To demonstrate the superiority of QVA149 27.5/12.5 µg b.i.d. compared to monotherapy components, QAB149 27.5 µg b.i.d. and NVA237 12.5 µg b.i.d., in terms of standardized FEV1AUC0-12 at Week 12.

Secondary Objective: Key secondary objective: To demonstrate the superiority of QVA149 27.5/12.5 µg b.i.d. compared to placebo at Week12 in terms of the change in Health Status, based on total score as well as the percentage of patients with clinically significant improvement, as reported by the patients using the SGRQ.
Secondary objectives
- To evaluate the superiority of QVA149 27.5/12.5 µg b.i.d., QAB149 27.5 µg b.i.d. and NVA237 12.5 µg b.i.d. compared to placebo in terms of standardized FEV1AUC0-12 at Wk 12.
- To evaluate the superiority of QVA149 27.5/12.5 µg b.i.d., QAB149 27.5 µg b.i.d. and NVA237 12.5 µg b.i.d. compared to placebo in terms of the following endpoints:
-trough FEV1 (mean of 23 h 15 min and 23 h 45 min post morning dose) at Wk 12
-pre-dose trough FEV1 (mean of 15 min and 45 min pre morning dose) at Week 12
-Trough FEV1 (mean of 23 h 15 min and 23 h 45 min post morning dose) after Day1
-FEV1 and FVC at any time point
Other secondary objectives listed in the protocol may apply

Timepoint(s) of evaluation of this end point: Timeframe : 12 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Timeframe :
1.2.3.4.5.6.7.9.10.11 : 12 weeks
8 : day 1

Secondary end point(s): 1-Total St. George's Respiratory Questionnaire score
2-Trough Forced Expiratory Volume in one second
3-Pre-dose trough Forced Expiratory Volume in one second
4-Transitional Dyspnea Index focal score
5-Number of puffs of rescue medication
6-Daily symptoms score
7-Trough Forced Expiratory Volume in one second
8-Forced Expiratory Volume in one second at any time point
9-Morning symptoms score
10-Evening symptoms scores
11-Forced Vital Capacity at different time points

Secondary ID(s)

CQVA149A2337

Source(s) of Monetary Support

Novartis Pharma Service AG