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: August 21, 2013
Last verified: August 2013
  Purpose

This study will assess 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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: NVA237 50 µg and indacaterol 150 µg
Drug: Placebo to NVA237 and indacaterol 150 µg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 445
Study Start Date: May 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01604278

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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01604278     History of Changes
Other Study ID Numbers: CNVA237A2316, 2011-005673-23
Study First Received: May 21, 2012
Last Updated: August 21, 2013
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Indacaterol
Glycopyrronium Bromide
COPD
bronchodilation

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Glycopyrrolate
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014