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)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: NVA237 50 µg and indacaterol 150 µg; Drug: Placebo to NVA237 and indacaterol 150 µg

• Study Type: Interventional
• Enrollment (Actual): 449
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1090
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1070
    • Novartis Investigative Site
  • Genk, Belgium, 3600
    • Novartis Investigative Site
  • Gilly, Belgium, 6060
    • Novartis Investigative Site
  • Gosselies, Belgium, 6041
    • Novartis Investigative Site
  • Hasselt, Belgium, 3500
    • Novartis Investigative Site
  • Herentals, Belgium, 2200
    • Novartis Investigative Site
  • Jambes, Belgium, 5100
    • Novartis Investigative Site
  • Liège, Belgium, 4000
    • Novartis Investigative Site
  • Luxembourg, Belgium, 1210
    • Novartis Investigative Site
  • Malmedy/Bellevaux-Ligneuville, Belgium, 4960
    • Novartis Investigative Site
  • Montigny-le-tilleul, Belgium, 6110
    • Novartis Investigative Site
  • Turnhout, Belgium, 2300
    • Novartis Investigative Site
  • Yvoir, Belgium, 5530
    • Novartis Investigative Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4002
    • Novartis Investigative Site
  • Ruse, Bulgaria, 7002
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1606
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1000
    • Novartis Investigative Site
  • Stara Zagora, Bulgaria, 6000
    • Novartis Investigative Site
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 11527
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 27
      • Novartis Investigative Site
    • Athens, GR, Greece, 106 76
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 564 03
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1121
    • Novartis Investigative Site
  • Budapest, Hungary, 1046
    • Novartis Investigative Site
  • Deszk, Hungary, 6772
    • Novartis Investigative Site
  • Erd, Hungary, H-2030
    • Novartis Investigative Site
  • Godollo, Hungary, 2100
    • Novartis Investigative Site
• Ireland
  • Cork
    • Wilton, Cork, Ireland
      • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 125315
    • Novartis Investigative Site
  • N.Novgorod, Russian Federation, 603126
    • Novartis Investigative Site
  • Nizhny Novgorod, Russian Federation, 603018
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410012
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 826 06
    • Novartis Investigative Site
  • Kosice, Slovakia, 040 01
    • Novartis Investigative Site
  • Kralovsky Chlmec, Slovakia, 077 01
    • Novartis Investigative Site
  • Slovak Republic
    • Bardejov, Slovak Republic, Slovakia, 085 01
      • Novartis Investigative Site
    • Bojnice, Slovak Republic, Slovakia, 972 01
      • Novartis Investigative Site
    • Liptovsky Hradok, Slovak Republic, Slovakia, 033 01
      • Novartis Investigative Site
  • Slovensko
    • Námestovo, Slovensko, Slovakia, 02901
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Asturias
    • Gijon, Asturias, Spain, 33290
      • Novartis Investigative Site
  • Cantabria
    • Torrelavega, Cantabria, Spain, 39300
      • Novartis Investigative Site
  • Castilla la Mancha
    • Illescas, Castilla la Mancha, Spain, 45200
      • Novartis Investigative Site
  • Castilla y Leon
    • Ponferrada, Castilla y Leon, Spain, 24400
      • Novartis Investigative Site
  • Cataluña
    • Centelles, Cataluña, Spain, 08540
      • Novartis Investigative Site
    • Salt, Cataluña, Spain, 17190
      • Novartis Investigative Site
    • Sant Boi de Llobregat, Cataluña, Spain, 08830
      • Novartis Investigative Site
    • Viladecans, Cataluña, Spain
      • Novartis Investigative Site
  • Extremadura
    • Mérida, Extremadura, Spain, 06800
      • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06490
    • Novartis Investigative Site
  • Istanbul, Turkey, 34854
    • Novartis Investigative Site
  • Istanbul, Turkey
    • Novartis Investigative Site
  • Kocaeli, Turkey, 41380
    • Novartis Investigative Site
  • Mersin, Turkey, 33079
    • Novartis Investigative Site
  • Yenisehir/Izmir, Turkey, 35110
    • Novartis Investigative Site
• United Kingdom
  • Bath, United Kingdom, BA1 2SR
    • Novartis Investigative Site
  • Bexhill-on-Sea, United Kingdom, TN40 1JJ
    • Novartis Investigative Site
  • Blackpool, United Kingdom, FY3 7EN
    • Novartis Investigative Site
  • Bradford, United Kingdom, BD9 6RJ
    • Novartis Investigative Site
  • Cambridge, United Kingdom, CB7 5JD
    • Novartis Investigative Site
  • Chesterfield, United Kingdom, S40 4AA
    • Novartis Investigative Site
  • Huntingdon, United Kingdom, PE29 6NT
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 2RN
    • Novartis Investigative Site
  • Newcastle-upon-Tyne, United Kingdom, NE7 7DN
    • Novartis Investigative Site
  • Newton Aycliffe, United Kingdom, DL5 4SE
    • Novartis Investigative Site
  • Reading, United Kingdom, RG7 3SQ
    • Novartis Investigative Site
  • Southbourne, United Kingdom
    • Novartis Investigative Site
  • Telford, United Kingdom, TF1 6TF
    • Novartis Investigative Site
  • Watford, United Kingdom, WD25 0EA
    • Novartis Investigative Site
  • Wiltshire, United Kingdom, SN15 2SB
    • Novartis Investigative Site
  • County Durham
    • Burnhope, County Durham, United Kingdom, DH7 0BD
      • Novartis Investigative Site
  • Suffolk
    • Alderton, Suffolk, United Kingdom, IP12 3DA
      • Novartis Investigative Site
  • Warwickshire
    • Atherstone, Warwickshire, United Kingdom, CV9 1EU
      • Novartis Investigative Site
    • Leamington Spa, Warwickshire, United Kingdom, CV32 4RA
      • Novartis Investigative Site
  • Yorkshire
    • Strensall, Yorkshire, United Kingdom, YO32 5UA
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NVA237 + indacaterol	Drug: NVA237 50 µg and indacaterol 150 µg; NVA237 50 µg and indacaterol 150 µg supplied as blistered capsules for inhalation.; Other Names: Glycopyrronium Bromide
Placebo Comparator: Placebo to NVA237 + indacaterol	Drug: Placebo to NVA237 and indacaterol 150 µg; Placebo to NVA237 and indacaterol 150 µg supplied as blistered capsules for inhalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume at 1 Second (FEV1)	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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV(1) Area Under the Curve (AUC) During 30 Minutes to 4 Hours Post Dose	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.	12 weeks
Peak FEV1 During 30 Minutes to 4 Hours Post-dose at 12 Weeks	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.	12 weeks
FEV1 at Individual Time-points	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.	Day 1, Day 29, Day 57 and Days 84/85
Forced Vital Capacity (FVC) at Individual Time-points	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.	Day 1, Day 29, Day 57 and Days 84/85
Inspiratory Capacity (IC) at Individual Time-points	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.	Day 1, Days 84/85
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication	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.	Baseline, 12 weeks
Transitional Dyspnea Index (TDI) Focal Score	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.	baseline, 12 weeks
Change From Baseline in Mean Daily Total and Individual Symptom Scores	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).	Baseline, 12 weeks
Number of Participants With Adverse Events and Serious Adverse Events	All study emergent adverse events including Chronic Obstructive Pulmonary Disease exacerbations were monitored from screening through the end of study.	12 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: May 21, 2012
• First Submitted That Met QC Criteria: May 21, 2012
• First Posted (Estimate): May 23, 2012

Study Record Updates

• Last Update Posted (Estimate): November 14, 2014
• Last Update Submitted That Met QC Criteria: November 12, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: COPD; Indacaterol; bronchodilation; Glycopyrronium Bromide
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Anticonvulsants; Glycopyrrolate; Bromides
• Other Study ID Numbers: CNVA237A2316; 2011-005673-23 (EudraCT Number)