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Efficacy, Safety and Tolerability of the Co-administration of NVA237 Plus Indacaterol Once Daily Versus Indacaterol Once Daily in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (GLOW6)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01604278
First received: May 21, 2012
Last updated: November 12, 2014
Last verified: November 2014

May 21, 2012
November 12, 2014
May 2012
January 2013   (final data collection date for primary outcome measure)
Trough Forced Expiratory Volume at 1 Second (FEV1) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Centralized spirometry according to internationally accepted standards was used. The model contained treatment, baseline smoking status and baseline inhaled corticosteroid (ICS) use as fixed effects with the baseline measurement of FEV1, FEV1 prior to inhalation of short acting bronchodilators and FEV1 post inhalation of short acting bronchodilator as covariates and center nested in region as a random effect. If trough FEV1 was missing at week 12, the latest non-missing pre-dose trough FEV1 (the mean of 45 and 15 min pre-dose measurements) from day 29, 57 or 84) was carried forward. These measurements had to have been taken before the next dose of study medication. FEV1 measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were not included in the analysis.
Comparison of 24 hours trough forced expiratory volume in 1 second after 12 weeks of each treatment. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Centralized spirometry according to internationally accepted standards. The primary analysis will be performed on the Full Analysis Set (FAS) population using a mixed model. The model will contain treatment as a fixed effect with the baseline measurement of trough forced expiratory volume in 1 second (FEV1), FEV1 prior to inhalation of short acting bronchodilator and FEV1 post inhalation of short acting bronchodilator as covariates.
Complete list of historical versions of study NCT01604278 on ClinicalTrials.gov Archive Site
  • FEV(1) Area Under the Curve (AUC) During 30 Minutes to 4 Hours Post Dose [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Centralized spirometry was used according to internationally accepted standards was used. The trapezoidal rule was applied to calculate FEV1 Area Under the Curve (AUC) and then normalized to the length of time. Whether the participants had complete or incomplete FEV1 assessments in respective time ranges, their AUCs were calculated based on the existing FEV1 measurements (i.e., the missing FEV1 measurements were not interpolated). Specifically, for those participants who had a FEV1 assessment at only one time-point, their AUC was approximated by the observed FEV1. FEV1 measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were not included in the analysis.
  • Peak FEV1 During 30 Minutes to 4 Hours Post-dose at 12 Weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Centralized spirometry was used according to internationally accepted standards was used. Peak FEV1 was defined as the maximum FEV1 during the first 4 hours post morning dosing. The model contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline measurement of FEV1, FEV1 prior to inhalation of short acting bronchodilators and FEV1 post inhalation of short acting bronchodilator as covariates and center nested in a region as a random effect. If all FEV1 measurements were missing from 30 minutes onward, the peak FEV1 was not calculated. FEV1 measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were not included in the analysis.
  • FEV1 at Individual Time-points [ Time Frame: Day 1, Day 29, Day 57 and Days 84/85 ] [ Designated as safety issue: No ]
    Centralized spirometry according to internationally accepted standards was used. FEV1 was measured at all post-dose time points up to 4 hours, and at 23 hours 15 minutes and 23 hours 45 minutes, by visit. The model contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline measurement of FEV1, FEV1 prior to inhaltion of short acting bronchodilators and FEV1 post inhaltion of short acting bronchodilators as covariates and center nested in region as a random effect. FEV1 measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were not included in the analysis.
  • Forced Vital Capacity (FVC) at Individual Time-points [ Time Frame: Day 1, Day 29, Day 57 and Days 84/85 ] [ Designated as safety issue: No ]
    FVC was calculated at each time point up to 4 hours post-dose and at 23 hours 15 minutes and 23 hours 45 minutes, by visit. The model contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline measurement of FVC, FEV1 prior to inhaltion of short acting bronchodilators and FEV1 post inhaltion of short acting bronchodilators as covariates and center nested in region as a random effect. FVC measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were set to missing.
  • Inspiratory Capacity (IC) at Individual Time-points [ Time Frame: Day 1, Days 84/85 ] [ Designated as safety issue: No ]
    Inspiratory Capacity (IC) was measured at 20 min pre-dose and at post-dose at 25 minutes, 1 hour 55 minutes, 3 hours 55 minutes and 23 hours 40 minutes, by visit. The model contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline measurement of IC, FEV1 prior to inhalation of short acting bronchodilators and FEV1 post inhalation of short acting bronchodilators as covariates and center nested in region as a random effect. IC measurements within 6 hours of rescue medication use or within 7 days of systemic corticosteroid use were set to missing.
  • Change From Baseline in Mean Daily Number of Puffs of Rescue Medication [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    The number of puffs of rescue medication taken in the previous 12 hours was recorded in the patient diary in the morning and evening. The total number of puffs of rescue medication per day over the whole active treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening), then a half day was used in the denominator.
  • Transitional Dyspnea Index (TDI) Focal Score [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    Dyspnea was measured at baseline using the Baseline Dyspnea Index (BDI) and during treatment using the Transitional Dyspnea Index (TDI). Analysis was done via mixed model. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort. BDI domains were rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranged from 0 to 12; lower scores mean worse severity. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of 1 is considered a minimal clinically important difference.
  • Change From Baseline in Mean Daily Total and Individual Symptom Scores [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    The symptoms (respiratory, cough, wheeze, sputum color, sputum production, breathlessness, sore throat, nasal discharge or congestion, and fever) for the whole active treatment period was analyzed using a mixed model, which contained treatment, baseline smoking status and baseline ICS use as fixed effects with the baseline symptom score, FEV1 prior to inhalation of short acting bronchodilators and FEV1 post inhalation of short acting bronchodilators as covariates and center nested in region as a random effect. Each symptom was scored as 0, 1, 2 or 3 where the description for each score varied. For each of the symptoms, the range of scores from 0 to 3 represented an increase in symptoms where 0 represented little to no symptom and 3 represented severe or worst symptom. The total symptom score, which is the sum of the individual scores, ranged from 0 (best possible outcome) to 27 (worst possible outcome).
  • Number of Participants With Adverse Events and Serious Adverse Events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    All study emergent adverse events including Chronic Obstructive Pulmonary Disease exacerbations were monitored from screening through the end of study.
  • Post dose treatment comparison of forced expiratory volume in 1 second / Area Under the Curve between 5 min and 4 hours [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Centralized spirometry according to internationally accepted standards. The trapezoidal rule will be used to calculate forced expiratory volume in 1 second (FEV1) Area Under the Curve (AUC). Whether the participants have complete or incomplete FEV1 assessments in respective time ranges, their AUCs will be calculated based on the existing FEV1 measurements. Specifically, for those patients who have FEV1 assessment at only one time-point, their AUC will be approximated by the observed FEV1.
  • Treatment comparison of peak forced expiratory volume in 1 second [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Centralized spirometry according to internationally accepted standards. Peak forced expiratory volume in 1 second (FEV1) is defined as the maximum FEV1 during the first 4 hours post morning dosing. The mixed model will contain treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilator and FEV1 post inhalation of short acting bronchodilator as covariates.
  • Treatment comparison of forced expiratory volume in 1 second at individual time-points [ Time Frame: Day 1, Day 29, Day 57 and Days 84/85 ] [ Designated as safety issue: No ]
    Centralized spirometry according to internationally accepted standards. Forced expiratory volume in 1 second (FEV1) is measured at all post-dose time points up to 4 hours, and at 23 hours 15 minutes and 23 hours 45 minutes, by visit. Mixed model uses baseline FEV1, baseline inhaled corticosteroid use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
  • Treatment comparison of forced vital capacity (FVC) at individual time-points [ Time Frame: Day 1, Day 29, Day 57 and Days 84/85 ] [ Designated as safety issue: No ]
    Forced Vital Capacity (FVC) is calculated at each time point up to 4 hours post-dose and at 23 hours 15 minutes and 23 hours 45 minutes, by visit. Mixed model uses baseline FVC, baseline inhaled corticosteroid use, forced expiratory volume in 1 second (FEV1) prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
  • Treatment comparison of Inspiratory Capacity (IC) at individual time-points [ Time Frame: Day 1, Day 29, Day 57 and Days 84/85 ] [ Designated as safety issue: No ]
    Inspiratory Capacity (IC) is measured at 20 minutes pre-dose and post-dose at 25 minutes, 1 hour 55 minutes, 3 hours 55 minutes and 23 hours 40 minutes, by visit. Mixed model uses baseline IC, baseline inhaled corticosteroid use, forced expiratory volume in 1 second (FEV1) prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 min post-inhalation of SABA as covariates.
  • Treatment comparison of mean change from baseline in daily number of puffs of rescue medication [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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. The total number of puffs of rescue medication per day over the whole active treatment period will be calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient.
  • Treatment comparison of Focal score of the Transitional Dyspnea Index (TDI) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Measured at baseline using the Baseline Dyspnea Index (BDI) and during treatment using the Transitional Dyspnea Index (TDI). Analysis will be done via mixed model. BDI domains rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranging from 0 to 12; lower scores mean worse severity. TDI domains are rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranging from -9 to 9; negative scores indicate deterioration. A TDI focal score of 1considered the minimal clinically important difference from baseline.
  • Treatment comparison throughout treatment period of symptoms via patient electronic diary [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The symptoms (respiratory, cough, wheeze, sputum color, sputum production, breathlessness, sore throat, nasal discharge or congestion, and fever) for the whole active treatment period will be analyzed using mixed model, with the baseline forced expiratory volume in 1 second (FEV1) term being replaced by the respective baseline symptoms.
  • Adverse Events and Serious Adverse Events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    All study emergent adverse events including Chronic Obstructive Pulmonary Disease exacerbations will be summarized and listed.
Not Provided
Not Provided
 
Efficacy, Safety and Tolerability of the Co-administration of NVA237 Plus Indacaterol Once Daily Versus Indacaterol Once Daily in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
A 12-week Multi-center, Randomized, Double-blind, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of the Co-administration of NVA237 + Indacaterol Once Daily vs. Indacaterol Once Daily in Patients With Moderate to Severe COPD

This study assessed the efficacy, safety and tolerability of the co-administration of NVA237 plus indacaterol taken once daily versus indacaterol taken once daily in patients with moderate to severe Chronic Obstructive Pulmonary Disease.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Chronic Obstructive Pulmonary Disease (COPD)
  • Drug: NVA237 50 µg and indacaterol 150 µg
    NVA237 50 µg and indacaterol 150 µg supplied as blistered capsules for inhalation.
    Other Name: Glycopyrronium Bromide
  • Drug: Placebo to NVA237 and indacaterol 150 µg
    Placebo to NVA237 and indacaterol 150 µg supplied as blistered capsules for inhalation.
  • Active Comparator: NVA237 + indacaterol
    Intervention: Drug: NVA237 50 µg and indacaterol 150 µg
  • Placebo Comparator: Placebo to NVA237 + indacaterol
    Intervention: Drug: Placebo to NVA237 and indacaterol 150 µg
Vincken W, Aumann J, Chen H, Henley M, McBryan D, Goyal P. Efficacy and safety of coadministration of once-daily indacaterol and glycopyrronium versus indacaterol alone in COPD patients: the GLOW6 study. Int J Chron Obstruct Pulmon Dis. 2014 Feb 24;9:215-28. doi: 10.2147/COPD.S51592. eCollection 2014.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
449
January 2013
January 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with moderate to severe stable Chronic Obstructive Lung Disease (COPD) Stage II or Stage III according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines.
  • Patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥ 30 % and/or <80 % of the predicted normal, and a post-bronchodilator FEV1/Forced Vital Capacity (FVC) < 0.70 at screening.
  • Current or ex-smokers who have a smoking history of at least 10 pack years
  • Symptomatic patients according to daily diary data.

Exclusion Criteria:

  • Pregnant or nursing (lactating) women.
  • Women of child-bearing potential unless using adequate contraception.
  • Patients with Type I or uncontrolled Type II diabetes.
  • Patients with a history of long time interval between start of Q wave and end of T wave in the heart's electrical cycle (QT) syndrome or whose QT corrected for heart rate (QTc) measured at screening (Visit 2) (Fridericia's method) is prolonged
  • Patients with paroxysmal (e.g. intermittent) atrial fibrillation
  • Patients who have a clinically significant electrocardiogram (ECG) or laboratory abnormality at screening (Visit 2)

Other protocol-defined inclusion/exclusion criteria may apply.

Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   Bulgaria,   Greece,   Hungary,   Ireland,   Russian Federation,   Slovakia,   Spain,   Turkey,   United Kingdom
 
NCT01604278
CNVA237A2316, 2011-005673-23
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
November 2014

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