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: 23 February 2015
• Main ID: EUCTR2012-003347-30-SK
• Date of registration: 14/08/2013
• Prospective Registration: No
• 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: 19/12/2012
• 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: DRA Department
• Affiliation: Novartis Slovakia s.r.o.

• Name: DRA Department
• Affiliation: Novartis Slovakia s.r.o.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients who have signed an Informed Consent Form prior to initiation
of any studyrelated procedure.
2. Male and female adults aged =40 years.
3. Patients with stable COPD according to the current GOLD strategy.
4. Patients with airflow limitation indicated by a post-bronchodilator
FEV1 = 30% and <80% of the predicted normal, and a postbronchodilator
FEV1/FVC < 0.70 at run-in (Visit 101). Post
bronchodilator refers to 1 hour after sequential inhalation of 84 µg
ipratropium bromide (or equivalent dose) and 400 µg salbutamol (or 360
µg albuterol). Spacer devices are not permitted during reversibility
testing.
5. Current or ex-smokers who have a smoking history of at least 10 pack
years (e.g.10 pack years = 1 pack /day x 10 years, or ½ pack/day x 20
years). An ex-smoker may be defined as a subject who has not smoked
for = 6 months at screening.
6. Patients with an mMRC grade 2 or greater at Visit 101.
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:
1. Pregnant or nursing (lactating) women, where pregnancy is defined
as the state of a female after conception and until the termination of
gestation, confirmed by a positive hCG (human Chorionic Gonadotropin)
laboratory test.
2. Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, unless they are using
effective methods of contraception during dosing of study treatment.
Effective contraception methods are described in the protocol.
3. Patients with Type I or uncontrolled Type II diabetes.
4. Patients with a history of long QT syndrome or whose QTc measured
at Visit 101 (Fridericia method) is prolonged (>450 ms for males and
females) and confirmed by a central assessor. These patients should not
be re-screened.
5. Patients who have a clinically significant ECG abnormality at Visit 101
or Visit 102. (These patients should not be re-screened)
6. Patients who have a clinically significant laboratory abnormality at
Visit 101.
7. Patients with a body mass index (BMI) of more than 40 kg/m2.
8. Patients who have clinically significant renal, cardiovascular (such as
but not limited to unstable ischemic heart disease, NYHA Class III/IV
left ventricular failure, myocardial infarction), arrhythmia (see below for
patients with atrial fibrillation), neurological, endocrine, immunological,
psychiatric, gastrointestinal, hepatic, or hematological abnormalities
which could interfere with the assessment of the efficacy and safety of
the study treatment.
9. Patients with paroxysmal (e.g. intermittent) atrial fibrillation are
excluded. Patients with persistent atrial fibrillation as defined by
continuous atrial fibrillation for at least 6 months and controlled with a
rate control strategy (i.e., selective beta blocker, calcium channel
blocker, pacemaker placement, digoxin or ablation therapy) for at least 6
months may be considered for inclusion. In such patients, atrial
fibrillation must be present at Visit 101 and Visit 102 visits with a resting
ventricular rate < 100/min. At Visit 101 the atrial fibrillation must be
confirmed by central reading.
10. 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:
• anticholinergic agents
• long and short acting beta-2 agonists
• sympathomimetic amines
• lactose or any of the other excipients of trial medication
For a full list of esclusion criteria, please refer to the protocol


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: 16.1 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
INN or Proposed INN: INDACATEROL
CAS Number: 753498-25-8
Current Sponsor code: QAB149
Other descriptive name: INDACATEROL MALEATE
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: 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.

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

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

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 Outcome(s)

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

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 ID(s)

CQVA149A2337

2012-003347-30-HU

Source(s) of Monetary Support

Novartis Pharma Service AG