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)

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— GLOW6  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01604278
• Other study ID #: CNVA237A2316
• Secondary ID: 2011-005673-23
• Status: Completed
• Phase: Phase 3
• First received: May 21, 2012
• Last updated: November 12, 2014
• Start date: May 2012
• Est. completion date: January 2013

Study information

• Verified date: November 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBulgaria: Bulgarian Drug AgencyGreece: National Organization of MedicinesHungary: National Institute of PharmacyIreland: Irish Medicines BoardRussia: Ministry of Health of the Russian FederationSlovakia: State Institute for Drug ControlSpain: Agencia Española de Medicamentos y Productos SanitariosTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 449
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• NVA237 50 µg and indacaterol 150 µg
NVA237 50 µg and indacaterol 150 µg supplied as blistered capsules for inhalation.
• Placebo to NVA237 and indacaterol 150 µg
Placebo to NVA237 and indacaterol 150 µg supplied as blistered capsules for inhalation.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Gilly
Belgium	Novartis Investigative Site	Gosselies
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Herentals
Belgium	Novartis Investigative Site	Jambes
Belgium	Novartis Investigative Site	Liège
Belgium	Novartis Investigative Site	Luxembourg
Belgium	Novartis Investigative Site	Malmedy/Bellevaux-Ligneuville
Belgium	Novartis Investigative Site	Montigny-le-tilleul
Belgium	Novartis Investigative Site	Turnhout
Belgium	Novartis Investigative Site	Yvoir
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Ruse
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Stara Zagora
Bulgaria	Novartis Investigative Site	Varna
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki	GR
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Deszk
Hungary	Novartis Investigative Site	Erd
Hungary	Novartis Investigative Site	Godollo
Ireland	Novartis Investigative Site	Wilton	Cork
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	N.Novgorod
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Saratov
Slovakia	Novartis Investigative Site	Bardejov	Slovak Republic
Slovakia	Novartis Investigative Site	Bojnice	Slovak Republic
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Kralovsky Chlmec
Slovakia	Novartis Investigative Site	Liptovsky Hradok	Slovak Republic
Slovakia	Novartis Investigative Site	Námestovo	Slovensko
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Centelles	Cataluña
Spain	Novartis Investigative Site	Gijon	Asturias
Spain	Novartis Investigative Site	Illescas	Castilla la Mancha
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Mérida	Extremadura
Spain	Novartis Investigative Site	Ponferrada	Castilla y Leon
Spain	Novartis Investigative Site	Salt	Cataluña
Spain	Novartis Investigative Site	Sant Boi de Llobregat	Cataluña
Spain	Novartis Investigative Site	Torrelavega	Cantabria
Spain	Novartis Investigative Site	Viladecans	Cataluña
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Mersin
Turkey	Novartis Investigative Site	Yenisehir/Izmir
United Kingdom	Novartis Investigative Site	Alderton	Suffolk
United Kingdom	Novartis Investigative Site	Atherstone	Warwickshire
United Kingdom	Novartis Investigative Site	Bath
United Kingdom	Novartis Investigative Site	Bexhill-on-Sea
United Kingdom	Novartis Investigative Site	Blackpool
United Kingdom	Novartis Investigative Site	Bradford
United Kingdom	Novartis Investigative Site	Burnhope	County Durham
United Kingdom	Novartis Investigative Site	Cambridge
United Kingdom	Novartis Investigative Site	Chesterfield
United Kingdom	Novartis Investigative Site	Huntingdon
United Kingdom	Novartis Investigative Site	Leamington Spa	Warwickshire
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Newcastle-upon-Tyne
United Kingdom	Novartis Investigative Site	Newton Aycliffe
United Kingdom	Novartis Investigative Site	Reading
United Kingdom	Novartis Investigative Site	Southbourne
United Kingdom	Novartis Investigative Site	Strensall	Yorkshire
United Kingdom	Novartis Investigative Site	Telford
United Kingdom	Novartis Investigative Site	Watford
United Kingdom	Novartis Investigative Site	Wiltshire

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Greece,  Hungary,  Ireland,  Russian Federation,  Slovakia,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes