A Study to Assess the Safety, Tolerability and Efficacy of NVA237 Versus Placebo

Chronic Obstructive Pulmonary Disease Clinical Trial

— GLOW 1  

Official title:

A 26-week Treatment, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of NVA237 in Patients With Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01005901
• Other study ID #: CNVA237A2304
• Secondary ID: 2009-013504-32
• Status: Completed
• Phase: Phase 3
• First received: October 30, 2009
• Last updated: March 15, 2012
• Start date: October 2009
• Est. completion date: December 2010

Study information

• Verified date: December 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSingapore: Health Sciences AuthoritySpain: Spanish Agency of MedicinesCanada: Health CanadaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationTurkey: Ministry of Health of Turkey General Directorate of Pharmaceuticals and PharmacyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaSouth Korea: Korea Food and Drug Administration (KFDA)Russia: Ministry of Health of the Russian FederationIndia: Drugs Controller General of IndiaRomania: National Medicines AgencyJapan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

A study to assess the safety, tolerability and efficacy of NVA237 versus placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1324
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008) and:

• Smoking history of at least 10 pack-years

• Post-bronchodilator FEV1 < 80% and = 30% of the predicted normal value

• Post-bronchodilator FEV1/FVC (forced vital capacity) < 70%

Exclusion Criteria:

1. Patients who have had a lower respiratory tract infection within 6 weeks prior to Visit 1

2. Patients with concomitant pulmonary disease

3. Patients with a history of asthma

4. Any patient with lung cancer or a history of lung cancer

5. Patients with a history of certain cardiovascular comorbid conditions

6. Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency

7. Patients in the active phase of a supervised pulmonary rehabilitation program

8. Patients contraindicated for tiotropium or ipratropium treatment or who have shown an untoward reaction to inhaled anticholinergic agents Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Glycopyrronium bromide
Glycopyrronium bromide 50µg was supplied as inhalation capsules for use via a Single Dose Dry Powder Inhaler (SDDPI)
• Placebo
Placebo inhalation capsules were provided for use via a SDDPI

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Daw Park SA
Canada	Novartis Investigative Site	Bridgewater	Nova Scotia
Canada	Novartis Investigative Site	Courtice	Ontario
Canada	Novartis Investigative Site	Mississuaga	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	North York	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Japan	Novartis Investigative Site	Asahikawa
Japan	Novartis Investigative Site	Hamakita
Japan	Novartis Investigative Site	Himeji
Japan	Novartis Investigative Site	Hitachi
Japan	Novartis Investigative Site	Kishiwada
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Matsue
Japan	Novartis Investigative Site	Matsusaka
Japan	Novartis Investigative Site	Moriya
Japan	Novartis Investigative Site	Naka-gun
Japan	Novartis Investigative Site	Obihiro
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Ota
Japan	Novartis Investigative Site	Otsu
Japan	Novartis Investigative Site	Sapporo
Japan	Novartis Investigative Site	Takatsuki
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Yabu
Japan	Novartis Investigative Site	Yonezawa
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Pusan
Korea, Republic of	Novartis Investigative site	Seoul
Netherlands	Novartis Investigative Site	Almelo
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Harderwijk
Netherlands	Novartis Investigative Site	Heerlen
Netherlands	Novartis Investigative Site	Zutphen
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Iasi
Romania	Novartis Investigative Site	Timisoara
Russian Federation	Novartis Investigative Site	Irkutsk
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Krasnodar
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	N. Novgorod
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Sochy
Russian Federation	Novartis Investigative Site	Stavropol
Russian Federation	Novartis Investigative Site	Yaroslavl
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Alicante
Spain	Novartis Investigative Site	Badalona
Spain	Novartis Investigative Site	Caceres
Spain	Novartis Investigative Site	Canet de Mar
Spain	Novartis Investigative Site	Centelles
Spain	Novartis Investigative Site	Valencia
Turkey	Novartis Investigative Site	Altunizade
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Diyarbakir
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kinikli/Denizli
Turkey	Novartis Investigative Site	Mersin
Turkey	Novartis Investigative Site	Soke/Aydin
Turkey	Novartis Investigative Site	Yenisehir/Izmir
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Bellevue	Nebraska
United States	Novartis Investigative Site	Biddeford	Maine
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Corpus Christi	Texas
United States	Novartis Investigative Site	Fairhope	Alabama
United States	Novartis Investigative Site	Glendale	Arizona
United States	Novartis Investigative Site	Johnson City	Tennessee
United States	Novartis Investigative Site	Kansas City	Missouri
United States	Novartis Investigative Site	Lincoln	Rhode Island
United States	Novartis Investigative Site	Livonia	Michigan
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Madisonville	Kentucky
United States	Novartis Investigative Site	McKinney	Texas
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Missoula	Montana
United States	Novartis Investigative Site	New Brunswick	New Jersey
United States	Novartis Investigative Site	Newark	Delaware
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Pikesville	Maryland
United States	Novartis Investigative Site	Port Orange	Florida
United States	Novartis Investigative Site	Reno	Nevada
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Slidell	Louisiana
United States	Novartis Investigative Site	St. Charles	Missouri
United States	Novartis Investigative Site	Tamarac	Florida
United States	Novartis Investigative Site	Topeka	Kansas
United States	Novartis Investigative Site	Tulsa	Oklahoma
United States	Novartis Investigative Site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Japan,  Korea, Republic of,  Netherlands,  Romania,  Russian Federation,  Singapore,  Spain,  Turkey, 

References & Publications (1)

D'Urzo A, Ferguson GT, van Noord JA, Hirata K, Martin C, Horton R, Lu Y, Banerji D, Overend T. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial. Respir Res. 2011 Dec 7;12:156. doi: 10.1186/1465-9921-12-156 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in 1 Second (FEV1) at 12 Weeks	Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.	12 weeks	No
Secondary	Transition Dyspnea Index (TDI) Focal Score After 26 Weeks of Treatment	Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. Mixed model used baseline TDI, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.	26 weeks	No
Secondary	Quality of Life Assessment With St. George's Respiratory Questionnaire (SGRQ) Total Score After 26 Weeks of Treatment	SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life. Mixed model used baseline SGRQ, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.	26 weeks	No
Secondary	Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During 26 Weeks of Treatment	The time to the first moderate or severe COPD exacerbation was the study day on which the patient experienced first moderate or severe COPD exacerbation. COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if treatment for moderate severity and hospitalization were required.	26 weeks	No
Secondary	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Medication Over the Study Duration (Baseline to Week 26)	Participants recorded the number of puffs of rescue medication taken in the previous 12 hours in the morning and evening. The total number of puffs of rescue medication per day over the full 26 weeks was calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the patient.	26 weeks	No
Secondary	FEV1 at Each Time-point on Day 1 and Week 26	Spirometry was conducted according to internationally accepted standards. FEV1 was measured at all time points up to 4 hours post-dose, and at 23 hours 15 min and 23 hours 45 min, by visit. Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.	Day 1 and Week 26	No
Secondary	Forced Vital Capacity (FVC) at Each Time-point on Day 1 and Week 26	Spirometry was conducted according to internationally accepted standards. FVC was calculated at each time point up to 4 hours post-dose and at 23 hours 15 min and 23 hours 45 min, by visit. Mixed model used baseline FVC, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.	Day 1 and Week 26	No
Secondary	FEV1 Area Under the Curve (AUC) (5 Min - 12 Hour) at Day 1, Week 12 and Week 26	The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 12 h post dose at Week 1 Day 1, Week 12 and Week 26 for every patient in the serial spirometry subgroup. Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.	Day 1, Week 12 and Week 26	No
Secondary	FEV1 Area Under Curve (AUC) (5 Min - 23 Hour 45 Min) at Week 12 and Week 26	The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 23 h 45 min post dose at week12/week 13and week 26/week 27 where available for every patient in the serial spirometry subgroup. Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.	Week 12 and Week 26	No
Secondary	Trough FEV1 and FVC at Day 1 and Week 26	Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.; Trough FVC was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FVC readings. Mixed model used baseline FVC, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.	Day 1 and Week 26	No
Secondary	Change in 24-hourly Mean Heart Rate at Day 1, Week 12 and Week 26	The mean heart rate was collected with a 24 hour Holter monitor in a sub-set of the safety population. The change between baseline and day 1, week 12 and week 26 was calculated. The analysis of the Holter recordings was performed by a central facility. Data on heart rate, heart rate variability, supraventricular and ventricular ectopy were collected and assessed.	Baseline, Day 1, Week 12 and Week 26	Yes
Secondary	Number of Participants With Adverse Events, Death, and Serious or Clinically Significant Adverse Events or Related Discontinuations	Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.	26 Weeks and 30 Day follow-up	Yes
Secondary	Rate of Moderate or Severe COPD Exacerbations Over the 26 Week Treatment Period	One overall rate is calculated for the entire study population. Rate is the number of moderate or severe exacerbations per year = total number of moderate or severe exacerbations for all participants/total number of treatment years for all participants. COPD exacerbations were considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations were considered to be severe if treatment for moderate severity and hospitalization were required.	26 weeks	No
Secondary	Percentage of Nights With no Nighttime Awakenings Over the 26 Week Treatment Period	The percentage of nights with no nighttime awakenings is defined as the total number of nights with no nighttime awakenings over the 26 week treatment period divided by the total number of night where diary recordings have been made.; Mixed model used baseline nighttime awakenings, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.	26 Weeks	No
Secondary	Percentage of Days With no Daytime Symptoms Over the 26 Week Treatment Period	The percentage of days with no daytime symptoms is defined as the total number of days with no daytime symptoms over the 26 week treatment period divided by the total number of days where diary recordings have been made.; Mixed model used baseline daytime symptoms, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.	26 Weeks	No
Secondary	Percentage of Days Able to Perform Usual Daily Activities Over the 26 Week Treatment Period	The percentage of days able to perform usual daily activities is defined as the total number of days able to perform usual activities over the 26 week treatment period divided by the total number of days where diary recordings have been made.; Mixed model used baseline ability to perform usual daily activities, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.	26 Weeks	No
Secondary	Mean Daily Total Symptom Score Over the 26 Week Treatment Period	The daily symptom score was calculated as the sum of the worst of the morning and evening assessments for each symptom (symptoms, cough, wheeze, sputum color/production, and breathlessness). The score can range from 0 to 18 with 0 indicating no symptoms. The higher the score, the worse the symptomatic status. A negative change (lower number) indicates improvement.; Mixed model used baseline symptom variables, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.	26 Weeks	No