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A 26-week Treatment Randomized, Double-blind, Double Dummy Study to Assess the Efficacy and Safety of QVA149

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01709903
Collaborator
(none)
744
Enrollment
56
Locations
2
Arms
15
Duration (Months)
13.3
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50 µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50 µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.

The study population will consist of approximate 736 male and female adults (age 40 years and greater) with a clinical diagnosis of stable COPD [GOLD (2010)] and a smoking history of at least 10 pack years. It is anticipated that approximately 981 patients will need to be screened in order to randomize 736 patients into 2 treatment arms of the study with an equal randomization ratio, meaning QVA149 (368 patients), fluticasone/salmeterol (368 patients). Treatment randomization will be stratified by current/ex-smoker status and prior ICS use. It is intended that 552 patients will complete the study at Week 26 without major protocol deviations. Dropouts will not be replaced.

This will be a multi-national study, including China, and at least two other countries.

Standardization FEV1 AUC0-12h will be performed in a subgroup of around 100 patients (50 patients per treatment arm) in pre-selected centers.

Study Design

Study Type:
Interventional
Actual Enrollment :
744 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A 26-week Treatment Randomized, Double-blind, Double Dummy, Parallel-group Study to Assess the Efficacy and Safety of QVA149 (Indacaterol / Glycopyrronium Bromide) Compared to Fluticasone/Salmeterol in Patients With Moderate to Severe COPD
Study Start Date :
Nov 1, 2012
Actual Primary Completion Date :
Feb 1, 2014
Actual Study Completion Date :
Feb 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: QVA149

QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg

Drug: QVA149
QVA149 110/50 µg capsules q.d. for inhalation, delivered via Novartis single dose dry powder inhaler (SDDPI).
Other Names:
  • Experimental: QVA149

    • Drug: Placebo to fluticasone/salmeterol
    Placebo to fluticasone/salmeterol with Accuhaler
    Other Names:
  • Comparator: fluticasone/salmeterol

    		•
    Active Comparator: fluticasone/salmeterol

    Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device

    Drug: Fluticasone/salmeterol
    Active fluticasone/salmeterol (500/50µg) b.i.d via a dry power inhaler Accuhaler® device.
    Other Names:
  • Comparator: Fluticasone/salmeterol

    • Drug: Placebo to QVA149
    Placebo to QVA149 with SDDPI
    Other Names:
  • Experimental: QVA149

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d [26 weeks]

      Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.

    Secondary Outcome Measures

    1. Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d [26 weeks]

    2. Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours [Day 1, 12 and 26 weeks]

      Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.

    3. Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period [6,12,18 and 26 weeks]

      Average of Trough Forced Expiratory Volume in one second (FEV1)

    4. Analysis of Trough FVC (L) Over the Whole Treatment Period [12 and 26 weeks]

      Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose

    5. Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment [26 weeks]

      A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.

    6. Analysis of the TDI Focal Score Over the Whole Treatment Period [12 and 26 weeks]

      The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. ."Baseline 12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point.

    7. Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals [12 and 26 weeks]

      The number of puffs of rescue medication taken in the previous 12 hours will be recorded in the Patient Diary in the morning and evening. "Baseline 12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point. Less puffs taken is better.

    8. Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment [26 weeks]

      Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients with moderate to severe stable COPD (Stage II or Stage III) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guideline.

    Current or ex-smokers who have a smoking history of at least 10 pack years. Patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥ 30% and < 80% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7.

    Modified Medical Research Council (mMRC) grade of at least 2 at Visit 2.

    Exclusion Criteria:
    • 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 Human Chorionic Gonadotropin (hCG) laboratory test.

    Patents with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH), bladder-neck obstruction, moderate to severe renal impairment or urinary retention. BPH patients who are stable on treatment can be considered.

    Patients with a history of long QT syndrome or whose QTc measured at run-in (Visit 2) (Fridericia method) is prolonged (>450 ms for males and females) as confirmed by the central Electrocardiogram (ECG) assessor.

    Patients with Type I or uncontrolled Type II diabetes. Patients who have not achieved spirometry result at Visit 2 in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria for acceptability and repeatability.

    Patients with, a) any history of asthma or, b) onset of respiratory symptoms prior to age 40 years.

    Patients with concomitant pulmonary disease (e.g. lung fibrosis, primary bronchiectasis, sarcoidosis, interstitial lung disorder, pulmonary hypertension).

    Other protocol-defined inclusion/exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Caba Buenos Aires Argentina 1122
    2 Novartis Investigative Site Caba Buenos Aires Argentina B8000XAV
    3 Novartis Investigative Site Caba Buenos Aires Argentina C1056ABJ
    4 Novartis Investigative Site Caba Buenos Aires Argentina C1280AEB
    5 Novartis Investigative Site Caba Buenos Aires Argentina C1424BSF
    6 Novartis Investigative Site Caba Buenos Aires Argentina C1425BEN
    7 Novartis Investigative Site La Plata Buenos Aires Argentina 1900
    8 Novartis Investigative Site Mar del Plata Buenos Aires Argentina 7600
    9 Novartis Investigative Site Rojas Buenos Aires Argentina B2705XAE
    10 Novartis Investigative Site San Miguel de Tucuman Tucuman Argentina T4000IFL
    11 Novartis Investigative Site Buenos Aires Argentina C1125ABE
    12 Novartis Investigative Site Cordoba Argentina X5016KEH
    13 Novartis Investigative Site Santiago Region Metropolitana Chile 8431633
    14 Novartis Investigative Site Santiago Region Metropolitana Chile
    15 Novartis Investigative Site Viña del Mar Vina del Mar Chile 2520024
    16 Novartis Investigative Site Santiago Chile Piso 1
    17 Novartis Investigative Site Santiago Chile
    18 Novartis Investigative Site Beijing Beijing China 100023
    19 Novartis Investigative Site Beijing Beijing China 100730
    20 Novartis Investigative Site Nanning Guangxi China 530021
    21 Novartis Investigative Site Shijiazhuang Hebei China 050000
    22 Novartis Investigative Site Wuhan Hubei China 430022
    23 Novartis Investigative Site Changsha City Hunan China 410011
    24 Novartis Investigative Site Changsha Hunan China 410003
    25 Novartis Investigative Site Nanjing Jiangsu China 210029
    26 Novartis Investigative Site Suzhou Jiangsu China 215004
    27 Novartis Investigative Site Nanchang Jiangxi China 330006
    28 Novartis Investigative Site Shengyang Liaoning China 110016
    29 Novartis Investigative Site Shenyang Liaoning China
    30 Novartis Investigative Site Qingdao Shandong China 266011
    31 Novartis Investigative Site Shanghai Shanghai China 200433
    32 Novartis Investigative Site Xi'an Shanxi China 710032
    33 Novartis Investigative Site Xi'an Shanxi China 710061
    34 Novartis Investigative Site Chengdu Sichuan China 610041
    35 Novartis Investigative Site Hangzhou Zhejiang China 310003
    36 Novartis Investigative Site Hangzhou Zhejiang China 310006
    37 Novartis Investigative Site Hangzhou Zhejiang China 310016
    38 Novartis Investigative Site Beijing China 100020
    39 Novartis Investigative Site Beijing China 100029
    40 Novartis Investigative Site Beijing China 100034
    41 Novartis Investigative Site Beijing China 100050
    42 Novartis Investigative Site Beijing China
    43 Novartis Investigative Site Chongqing China 400037
    44 Novartis Investigative Site Chongqing China 400038
    45 Novartis Investigative Site Chongqing China 400042
    46 Novartis Investigative Site Jiangyin China
    47 Novartis Investigative Site Nanjing China
    48 Novartis Investigative Site Shanghai China 200032
    49 Novartis Investigative Site Shanghai China 200080
    50 Novartis Investigative Site Shanghai China 200433
    51 Novartis Investigative Site Taipei Taiwan, ROC Taiwan 112
    52 Novartis Investigative Site Kaohsiung Taiwan 81346
    53 Novartis Investigative Site Lin-Ko Taiwan 33305
    54 Novartis Investigative Site Niaosong Township Taiwan 83301
    55 Novartis Investigative Site Taichung Taiwan 40705
    56 Novartis Investigative Site Taipei County Taiwan

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01709903
    Other Study ID Numbers:
    • CQVA149A2331
    First Posted:
    Oct 18, 2012
    Last Update Posted:
    Mar 17, 2015
    Last Verified:
    Mar 1, 2015
    Keywords provided by Novartis Pharmaceuticals
    chronic obstructive pulmonary disease
    Additional relevant MeSH terms:
    Lung Diseases
    Lung Diseases, Obstructive
    Pulmonary Disease, Chronic Obstructive
    Fluticasone
    Xhance
    Glycopyrrolate
    Salmeterol Xinafoate
    Fluticasone-Salmeterol Drug Combination

    Study Results

    Participant Flow

    Recruitment Details Patients were randomized into 2 treatment arms of the study with an equal 1:1 randomization ratio: QVA149 and Flut/Salm
    Pre-assignment Detail A total of 1189 patients were screened; 744 (62.6%) completed the screening phase while 445 (37.4%) patients discontinued prior to completion of the screening phase
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Period Title: Overall Study
    STARTED 372 372
    COMPLETED 343 333
    NOT COMPLETED 29 39

    Baseline Characteristics

    Arm/Group Title QVA149 Fluticasone/Salmeterol Total
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device Total of all reporting groups
    Overall Participants 372 369 741
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64.8
    (7.82)
    65.3
    (7.91)
    65.0
    (7.87)
    Sex: Female, Male (Count of Participants)
    Female
    31
    8.3%
    38
    10.3%
    69
    9.3%
    Male
    341
    91.7%
    331
    89.7%
    672
    90.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    0.3%
    2
    0.5%
    3
    0.4%
    Asian
    314
    84.4%
    309
    83.7%
    623
    84.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    55
    14.8%
    58
    15.7%
    113
    15.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    2
    0.5%
    0
    0%
    2
    0.3%

    Outcome Measures

    1. Primary Outcome
    Title Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
    Description Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.
    Time Frame 26 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Measure Participants 372 369
    Least Squares Mean (Standard Error) [liters]
    1.248
    (0.0173)
    1.176
    (0.0172)
    2. Secondary Outcome
    Title Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
    Description
    Time Frame 26 weeks

    Outcome Measure Data

    Analysis Population Description
    FAS
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Measure Participants 372 369
    Least Squares Mean (Standard Error) [liters]
    1.259
    (.0170)
    1.183
    (0.0168)
    3. Secondary Outcome
    Title Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours
    Description Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.
    Time Frame Day 1, 12 and 26 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis set
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Measure Participants 372 369
    Day 1 (n=369,364)
    1.317
    (0.0096)
    1.252
    (0.0094)
    12 weeks (n=350,338)
    1.388
    (0.0163)
    1.262
    (0.0161)
    26 weeks (n=339,323)
    1.351
    (0.0167)
    1.229
    (0.0167)
    4. Secondary Outcome
    Title Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period
    Description Average of Trough Forced Expiratory Volume in one second (FEV1)
    Time Frame 6,12,18 and 26 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Measure Participants 372 369
    Week 6 (n=356,341)
    1.256
    (0.0151)
    1.184
    (0.0149)
    week 12 (n=346,333)
    1.265
    (0.0158)
    1.191
    (0.0156)
    week 18 (n=339,332)
    1.252
    (0.0166)
    1.174
    (0.0164)
    week 26 (n=338,324)
    1.226
    (0.0171)
    1.142
    (0.0171)
    5. Secondary Outcome
    Title Analysis of Trough FVC (L) Over the Whole Treatment Period
    Description Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose
    Time Frame 12 and 26 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Measure Participants 372 369
    Day 1 (n=350,351)
    3.040
    (0.0288)
    2.957
    (0.0280)
    Week 12 (n=342,332)
    3.036
    (0.0304)
    2.835
    (0.0302)
    week 26 (n= 333,323)
    2.966
    (0.0334)
    2.793
    (0.0333)
    6. Secondary Outcome
    Title Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment
    Description A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.
    Time Frame 26 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis set
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Measure Participants 372 369
    Week 26 (n= 340,329)
    31.20
    (1.118)
    32.00
    (1.118)
    Week 26 LOCF(n=354,342)
    31.74
    (1.136)
    32.43
    (1.130)
    7. Secondary Outcome
    Title Analysis of the TDI Focal Score Over the Whole Treatment Period
    Description The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. ."Baseline 12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point.
    Time Frame 12 and 26 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Measure Participants 372 369
    Baseline 12 weeks (n=348,337)
    6.36
    (0.096)
    6.36
    (0.104)
    12 weeks (n=348,337)
    2.62
    (0.240)
    2.40
    (0.238)
    Baseline 26 weeks (n=335,326)
    6.38
    (0.097)
    6.40
    (0.105)
    26 weeks (n=335,326)
    3.02
    (0.266)
    2.86
    (0.266)
    8. Secondary Outcome
    Title Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals
    Description The number of puffs of rescue medication taken in the previous 12 hours will be recorded in the Patient Diary in the morning and evening. "Baseline 12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point. Less puffs taken is better.
    Time Frame 12 and 26 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis set
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Measure Participants 372 369
    Baseline Daytime 12-16 weeks (n=329,318)
    1.57
    (1.934)
    1.69
    (2.130)
    Daytime 12-16 weeks (n=329,318)
    0.66
    (1.185)
    0.61
    (1.117)
    Baseline Nighttime 12-16 weeks (n=322,307)
    1.25
    (1.5954)
    1.24
    (1.707)
    Nighttime 12-16 weeks (n=322,307)
    0.52
    (1.007)
    0.49
    (0.960)
    Baseline Daytime 24-26 weeks (n=326,315)
    1.54
    (1.885)
    1.70
    (2.160)
    Daytime 24-26 weeks (n=326,315)
    0.63
    (1.226)
    0.62
    (1.135)
    Baseline Night time 24-26 weeks (n=320,304)
    1.23
    (1.588)
    1.21
    (1.702)
    Night time 24-26 weeks (n=320,304)
    0.52
    (1.087)
    0.48
    (0.923)
    9. Secondary Outcome
    Title Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment
    Description Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS)
    Time Frame 26 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title QVA149 Fluticasone/Salmeterol
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Measure Participants 372 369
    % nights 'no nighttime awakenings' (n=336,322)
    67.57
    (2.138)
    67.86
    (2.101)
    % days with 'no daytime symptoms' (n=341,334)
    7.31
    (1.466)
    10.22
    (1.425)
    % days able perform daily activities (n=341,334)
    44.02
    (2.200)
    42.16
    (2.140)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title QVA149 110mcg/50mcg Salmeterol/Fluticasone 50mcg/500mcg
    Arm/Group Description QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    All Cause Mortality
    QVA149 110mcg/50mcg Salmeterol/Fluticasone 50mcg/500mcg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    QVA149 110mcg/50mcg Salmeterol/Fluticasone 50mcg/500mcg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/372 (5.4%) 35/369 (9.5%)
    Blood and lymphatic system disorders
    Thrombocytopenia 0/372 (0%) 1/369 (0.3%)
    Cardiac disorders
    Acute myocardial infarction 1/372 (0.3%) 0/369 (0%)
    Angina pectoris 0/372 (0%) 1/369 (0.3%)
    Arteriosclerosis coronary artery 0/372 (0%) 1/369 (0.3%)
    Atrial fibrillation 0/372 (0%) 1/369 (0.3%)
    Cardiac arrest 0/372 (0%) 1/369 (0.3%)
    Cardiac failure 0/372 (0%) 1/369 (0.3%)
    Cardiac failure congestive 1/372 (0.3%) 0/369 (0%)
    Cardio-respiratory arrest 0/372 (0%) 1/369 (0.3%)
    Cor pulmonale 1/372 (0.3%) 0/369 (0%)
    Cor pulmonale chronic 0/372 (0%) 1/369 (0.3%)
    Coronary artery disease 0/372 (0%) 1/369 (0.3%)
    Right ventricular dysfunction 1/372 (0.3%) 0/369 (0%)
    Eye disorders
    Conjunctivitis 0/372 (0%) 1/369 (0.3%)
    Pterygium 1/372 (0.3%) 0/369 (0%)
    Gastrointestinal disorders
    Inguinal hernia 0/372 (0%) 1/369 (0.3%)
    Large intestine polyp 0/372 (0%) 2/369 (0.5%)
    Upper gastrointestinal haemorrhage 1/372 (0.3%) 0/369 (0%)
    General disorders
    Hyperplasia 0/372 (0%) 1/369 (0.3%)
    Sudden cardiac death 1/372 (0.3%) 0/369 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/372 (0%) 1/369 (0.3%)
    Cholelithiasis 0/372 (0%) 1/369 (0.3%)
    Hepatic failure 0/372 (0%) 1/369 (0.3%)
    Hepatic function abnormal 0/372 (0%) 2/369 (0.5%)
    Infections and infestations
    Bronchitis 0/372 (0%) 1/369 (0.3%)
    Gastroenteritis 0/372 (0%) 1/369 (0.3%)
    Lung infection 1/372 (0.3%) 2/369 (0.5%)
    Pneumonia 2/372 (0.5%) 4/369 (1.1%)
    Septic shock 0/372 (0%) 2/369 (0.5%)
    Upper respiratory tract infection bacterial 0/372 (0%) 1/369 (0.3%)
    Injury, poisoning and procedural complications
    Laceration 0/372 (0%) 1/369 (0.3%)
    Metabolism and nutrition disorders
    Hyponatraemia 0/372 (0%) 1/369 (0.3%)
    Type 2 diabetes mellitus 1/372 (0.3%) 0/369 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/372 (0%) 1/369 (0.3%)
    Gastric cancer 1/372 (0.3%) 0/369 (0%)
    Lung neoplasm malignant 0/372 (0%) 1/369 (0.3%)
    Rectal cancer 1/372 (0.3%) 0/369 (0%)
    Nervous system disorders
    Cerebral infarction 2/372 (0.5%) 1/369 (0.3%)
    Vertebrobasilar insufficiency 0/372 (0%) 1/369 (0.3%)
    Renal and urinary disorders
    Renal failure 0/372 (0%) 2/369 (0.5%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 1/372 (0.3%) 0/369 (0%)
    Chronic obstructive pulmonary disease 6/372 (1.6%) 17/369 (4.6%)
    Lung cyst 0/372 (0%) 1/369 (0.3%)
    Pneumothorax 0/372 (0%) 1/369 (0.3%)
    Pneumothorax spontaneous 1/372 (0.3%) 0/369 (0%)
    Respiratory failure 0/372 (0%) 2/369 (0.5%)
    Vascular disorders
    Aortic aneurysm 1/372 (0.3%) 0/369 (0%)
    Hypotension 0/372 (0%) 1/369 (0.3%)
    Other (Not Including Serious) Adverse Events
    QVA149 110mcg/50mcg Salmeterol/Fluticasone 50mcg/500mcg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 107/372 (28.8%) 135/369 (36.6%)
    Gastrointestinal disorders
    Gastritis 0/372 (0%) 4/369 (1.1%)
    General disorders
    Pyrexia 3/372 (0.8%) 5/369 (1.4%)
    Infections and infestations
    Bronchitis 7/372 (1.9%) 3/369 (0.8%)
    Nasopharyngitis 30/372 (8.1%) 45/369 (12.2%)
    Pneumonia 1/372 (0.3%) 6/369 (1.6%)
    Upper respiratory tract infection 13/372 (3.5%) 26/369 (7%)
    Upper respiratory tract infection bacterial 5/372 (1.3%) 3/369 (0.8%)
    Viral upper respiratory tract infection 1/372 (0.3%) 5/369 (1.4%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 69/372 (18.5%) 83/369 (22.5%)
    Dyspnoea 2/372 (0.5%) 6/369 (1.6%)
    Oropharyngeal pain 2/372 (0.5%) 6/369 (1.6%)
    Vascular disorders
    Hypertension 3/372 (0.8%) 5/369 (1.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01709903
    Other Study ID Numbers:
    • CQVA149A2331
    First Posted:
    Oct 18, 2012
    Last Update Posted:
    Mar 17, 2015
    Last Verified:
    Mar 1, 2015