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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01709903
Recruitment Status : Completed
First Posted : October 18, 2012
Results First Posted : March 17, 2015
Last Update Posted : March 17, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE October 16, 2012
First Posted Date  ICMJE October 18, 2012
Results First Submitted Date  ICMJE February 27, 2015
Results First Posted Date  ICMJE March 17, 2015
Last Update Posted Date March 17, 2015
Study Start Date  ICMJE November 2012
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2015)
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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 16, 2012)
Trough Forced Expiratory Volume in one second (FEV1) [ Time Frame: 26 weeks ]
Mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose
Change History Complete list of historical versions of study NCT01709903 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2015)
  • 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 [ Time Frame: 26 weeks ]
  • Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours [ Time Frame: 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.
  • Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period [ Time Frame: 6,12,18 and 26 weeks ]
    Average of Trough Forced Expiratory Volume in one second (FEV1)
  • Analysis of Trough FVC (L) Over the Whole Treatment Period [ Time Frame: 12 and 26 weeks ]
    Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose
  • Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment [ Time Frame: 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.
  • Analysis of the TDI Focal Score Over the Whole Treatment Period [ Time Frame: 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.
  • Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals [ Time Frame: 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.
  • Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment [ Time Frame: 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2012)
  • Standardized Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC) 0-12 hours [ Time Frame: 12 and 26 weeks ]
    The trapezoidal rule will be used to calculate Forced Expiratory Volume in one second Area under the curve.
  • Trough Forced Expiratory Volume in one second (FEV1) and Forced Vital Capacity (FVC) [ Time Frame: 12 and 26 weeks ]
    Average of Trough Forced Expiratory Volume in one second (FEV1) and Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose
  • Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours [ Time Frame: 12 and 26 weeks ]
    The trapezoidal rule will be used to calculate Forced Expiratory Volume in one second Area under the curve.
  • Health Related Quality of Life [ Time Frame: 12 and 26 weeks ]
    The total score of St.George Respiratory Questionnaire (SGRQ)
  • Dyspnea [ Time Frame: 12 and 26 weeks ]
    Dyspnea will be measured at baseline using the baseline dyspnea index (BDI) and during the treatment period using the transitional dyspnea index (TDI), which captures changes from baseline.
  • Rescue medication use [ Time Frame: 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.
  • Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment [ Time Frame: 12 and 26 weeks ]
    Will be recorded in the Patient Diary in the morning and evening
  • Safety and tolerability [ Time Frame: 26 weeks ]
    Electrocardiograms(ECGs), laboratory tests, blood pressure, heart rate and adverse events including Chronic Obstructive Pulmonary Disease (COPD) exacerbations and oral candidiasis.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A 26-week Treatment Randomized, Double-blind, Double Dummy Study to Assess the Efficacy and Safety of QVA149
Official Title  ICMJE 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
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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Obstructive Pulmonary Disease
Intervention  ICMJE
  • Drug: QVA149
    QVA149 110/50 µg capsules q.d. for inhalation, delivered via Novartis single dose dry powder inhaler (SDDPI).
    Other Name: Experimental: QVA149
  • Drug: Fluticasone/salmeterol
    Active fluticasone/salmeterol (500/50µg) b.i.d via a dry power inhaler Accuhaler® device.
    Other Name: Comparator: Fluticasone/salmeterol
  • Drug: Placebo to QVA149
    Placebo to QVA149 with SDDPI
    Other Name: Experimental: QVA149
  • Drug: Placebo to fluticasone/salmeterol
    Placebo to fluticasone/salmeterol with Accuhaler
    Other Name: Comparator: fluticasone/salmeterol
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: QVA149
    • Drug: Placebo to fluticasone/salmeterol
  • Active Comparator: fluticasone/salmeterol
    Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
    Interventions:
    • Drug: Fluticasone/salmeterol
    • Drug: Placebo to QVA149
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 13, 2015)
744
Original Estimated Enrollment  ICMJE
 (submitted: October 16, 2012)
736
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Chile,   China,   Taiwan
Removed Location Countries Brazil
 
Administrative Information
NCT Number  ICMJE NCT01709903
Other Study ID Numbers  ICMJE CQVA149A2331
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP