A Study to Assess the Efficacy, Safety and Tolerability of Once-daily (q.d.) QVA149 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (SHINE)

A 26-week Treatment Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled (Open Label) Study to Assess the Efficacy, Safety and Tolerability of QVA149 (110/50 μg q.d.) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

The purpose of this study is to provide pivotal efficacy and safety data for QVA149 in patients with moderate to severe COPD.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: indacaterol and glycopyrronium (QVA149); Drug: glycopyrronium (NVA237); Drug: indacaterol (QAB149); Drug: tiotropium; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 2144
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Daw Park, Australia
    • Novartis Investigative Site
  • Glebe, Australia
    • Novartis Investigative Site
  • Kogarah, Australia
    • Novartis Investigative Site
  • Nedlands, Australia
    • Novartis Investigative Site
  • New lambton, Australia
    • Novartis Investigative Site
• Bulgaria
  • Pleven, Bulgaria
    • Novartis Investigative Site
  • Russe, Bulgaria
    • Novartis Investigative Site
  • Sofia, Bulgaria
    • Novartis Investigative Site
  • Stara Zagora, Bulgaria
    • Novartis Investigative Site
  • Varna, Bulgaria
    • Novartis Investigative Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Novartis Investigative Site
  • Ontario
    • Burlington, Ontario, Canada
      • Novartis Investigative Site
    • Courtice, Ontario, Canada
      • Novartis Investigative Site
    • Mississuaga, Ontario, Canada
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada
      • Novartis Investigative Site
    • Toronto, Ontario, Canada
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada
      • Novartis Investigative Site
• France
  • Beuvry, France
    • Novartis Investigative Site
  • Bourges, France
    • Novartis Investigative Site
  • Ferolles-Attily, France
    • Novartis Investigative Site
  • Rennes, France
    • Novartis Investigative Site
• Germany
  • Berlin, Germany
    • Novartis Investigative Site
  • Erfurt, Germany
    • Novartis Investigative Site
  • Geesthacht, Germany
    • Novartis Investigative Site
  • Hanover, Germany
    • Novartis Investigative Site
  • Leipzig, Germany
    • Novartis Investigative Site
  • Minden, Germany
    • Novartis Investigative Site
  • Witten, Germany
    • Novartis Investigative Site
• Guatemala
  • Guatemala City, Guatemala
    • Novartis Investigative Site
• Hungary
  • Balassagyarmat, Hungary
    • Novartis Investigative Site
  • Budapest, Hungary
    • Novartis Investigative Site
  • Gyor, Hungary
    • Novartis Investigative Site
  • Komarom, Hungary
    • Novartis Investigative Site
  • Nyiregyhaza, Hungary
    • Novartis Investigative Site
  • Tatabanya, Hungary
    • Novartis Investigative Site
• Japan
  • Asahikawa, Japan
    • Novartis Investigative Site
  • Chiba, Japan
    • Novartis Investigative Site
  • Chuo-ku, Japan
    • Novartis Investigative Site
  • Fukuoka, Japan
    • Novartis Investigative Site
  • Hachioji, Japan
    • Novartis Investigative Site
  • Hamakita, Japan
    • Novartis Investigative Site
  • Himeji, Japan
    • Novartis Investigative Site
  • Hiroshima, Japan
    • Novartis Investigative Site
  • Hitachi, Japan
    • Novartis Investigative Site
  • Itabashi, Japan
    • Novartis Investigative Site
  • Iwata, Japan
    • Novartis Inverstigative Site
  • Kamogawa, Japan
    • Novartis Investigative Site
  • Kishiwada, Japan
    • Novartis Investigative Site
  • Kiyose, Japan
    • Novartis Investigative Site
  • Kurashiki, Japan
    • Novartis Investigative Site
  • Matsusaka, Japan
    • Novartis Investigative Site
  • Matumoto, Japan
    • Novartis Investigative Site
  • Minato-ku, Japan
    • Novartis Investigative Site
  • Moriya, Japan
    • Novartis Investigative Site
  • Nagaoka, Japan
    • Novartis Investigative Site
  • Nagoya, Japan
    • Novartis Investigative Site
  • Niigata, Japan
    • Novartis Investigative Site
  • Obihiro, Japan
    • Novartis Investigative Site
  • Sakai, Japan
    • Novartis Investigative Site
  • Sakaide, Japan
    • Novartis Investigative Site
  • Sapporo, Japan
    • Novartis Investigative Site
  • Tachikawa, Japan
    • Novartis Investigative Site
  • Takatsuki, Japan
    • Novartis Investigative Site
  • Tsu, Japan
    • Novartis Investigative Site
  • Yabu, Japan
    • Novartis Investigative Site
  • Yanagawa, Japan
    • Novartis Investigative Site
  • Yatsushiro, Japan
    • Novartis Investigative Site
  • Yonezawa, Japan
    • Novartis Investigative Site
• Philippines
  • Bulacan, Philippines
    • Novartis Investigative Site
  • Las Pinas City, Philippines
    • Novartis Investigative Site
  • Manila, Philippines
    • Novartis Investigative Site
  • Pasay City, Philippines
    • Novartis Investigative Site
  • Quezon City, Philippines
    • Novartis Investigative Site
• Poland
  • Krakow, Poland
    • Novartis Investigative Site
  • Proszowice, Poland
    • Novartis Investigative Site
  • Tarnov, Poland
    • Novartis Investigative Site
  • Warsaw, Poland
    • Novartis Investigative Site
• Russian Federation
  • Barnaul, Russian Federation
    • Novartis Investigative Site
  • Kazan, Russian Federation
    • Novartis Investigative Site
  • Moscow, Russian Federation
    • Novartis Investigative Site
  • Nizhny Novgorod, Russian Federation
    • Novartis Investigative Site
  • Nizhny Novogorod, Russian Federation
    • Novartis Investigative Site
  • Samara, Russian Federation
    • Novartis Investigative Site
  • Saratov, Russian Federation
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation
    • Novartis Investigative Site
  • Ufa, Russian Federation
    • Novartis Investigative Site
• Slovakia
  • Bardejov, Slovakia
    • Novartis Investigative Site
  • Bojnice, Slovakia
    • Novartis Investigative Site
  • Bratislava, Slovakia
    • Novartis Investigative Site
  • Humenne, Slovakia
    • Novartis Investigative Site
  • Kosice, Slovakia
    • Novartis Investigative Site
  • Liptovsky Hradok, Slovakia
    • Novartis Investigative Site
  • Partizanske, Slovakia
    • Novartis Investigative Site
  • Prievidza, Slovakia
    • Novartis Investigative Site
  • Spisska Nova Ves, Slovakia
    • Novartis Investigative Site
  • Trstena, Slovakia
    • Novartis Investigative Site
  • Zilina, Slovakia
    • Novartis Investigative Site
  • Zvolen, Slovakia
    • Novartis Investigative Site
• South Africa
  • Cape Town, South Africa
    • Novartis Investigative Site
  • Durban, South Africa
    • Novartis Investigative Site
  • Johannesburg, South Africa
    • Novartis Investigative Site
  • Lyttleton, South Africa
    • Novartis Investigative Site
  • Pretoria, South Africa
    • Novartis Investigative Site
• Spain
  • Alcira, Spain
    • Novartis Investigative Site
  • Badalona, Spain
    • Novartis Investigative Site
  • Barcelona, Spain
    • Novartis Investigative Site
  • Canet de Mar, Spain
    • Novartis Investigative Site
  • Centelles, Spain
    • Novartis Investigative Site
  • Ferrol, Spain
    • Novartis Investigative Site
  • Fuenlabrada, Spain
    • Novartis Investigative Site
  • Les Borges del Camp, Spain
    • Novartis Investigative Site
  • Madrid, Spain
    • Novartis Investigative Site
  • Mataro, Spain
    • Novartis Investigative Site
  • Merida, Spain
    • Novartis Investigative Site
  • Mostoles, Spain
    • Novartis Investigative Site
  • Motril, Spain
    • Novartis Investigative Site
  • Palma de Mallorca, Spain
    • Novartis Investigative Site
  • Ponferrada, Spain
    • Novartis Investigative Site
  • Salamanca, Spain
    • Novartis Investigative Site
  • Salt, Spain
    • Novartis Investigative Site
  • Valencia, Spain
    • Novartis Investigative Site
  • Vic, Spain
    • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland
    • Novartis Investigative Site
  • Lugano, Switzerland
    • Novartis Investigative Site
  • Munchenstein, Switzerland
    • Novartis Investigative Site
  • Neuchatel, Switzerland
    • Novartis Investigative Site
  • Zurich, Switzerland
    • Novartis Investigative Site
• Taiwan
  • Chai-Yi, Taiwan
    • Novartis Investigative Site
  • Kaohsiung, Taiwan
    • Novartis Investigative Site
  • Taichung, Taiwan
    • Novartis Investigative Site
  • Taipei, Taiwan
    • Novartis Investigative Site
• Turkey
  • Adana, Turkey
    • Novartis Investigative Site
  • Ankara, Turkey
    • Novartis Investigative Site
  • Bolu, Turkey
    • Novartis Investigative Site
  • Bursa, Turkey
    • Novartis Investigative Site
  • Canakkale, Turkey
    • Novartis Investigative Site
  • Denizli, Turkey
    • Novartis Investigative Site
  • Istanbul, Turkey
    • Novartis Investigative Site
  • Izmir, Turkey
    • Novartis Investigative Site
  • Kocaeli, Turkey
    • Novartis Investigative Site
  • Manisa, Turkey
    • Novartis Investigative Site
  • Mersin, Turkey
    • Novartis Investigative Site
• United Kingdom
  • Bath, United Kingdom
    • Novartis Investigative Site
  • Blackpool, United Kingdom
    • Novartis Investigative Site
  • Bradford, United Kingdom
    • Novartis Investigative Site
  • Cambs, United Kingdom
    • Novartis Investigative Site
  • Chelmsford, United Kingdom
    • Novartis Investigative Site
  • Chesterfield, United Kingdom
    • Novartis Investigative Site
  • Glasgow, United Kingdom
    • Novartis Investigative Site
  • Herts, United Kingdom
    • Novartis Investigative Site
  • Isle of Wight, United Kingdom
    • Novartis Investigative Site
  • London, United Kingdom
    • Novartis Investigative Site
• United States
  • California
    • Fullerton, California, United States, 92835
      • Novartis Investigative Site
    • Riverside, California, United States, 92506
      • Novartis Investigative Site
  • Florida
    • St. Petersburg, Florida, United States, 33707
      • Novartis Investigative Site
  • Michigan
    • Troy, Michigan, United States, 48085
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Novartis Investigative Site
  • Missouri
    • St. Charles, Missouri, United States, 63301
      • Novartis Investigative Site
    • St. Louis, Missouri, United States, 63141
      • Novartis Investigative Site
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Novartis Investigative Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Novartis Investigative Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Novartis Investigative Site
    • Portland, Oregon, United States, 97213
      • Novartis Investigative Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Novartis Investigative Site
  • Tennessee
    • Johnson City, Tennessee, United States, 37601
      • 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:

• Male or female adults aged ≥40 yrs
• Smoking history of at least 10 pack years
• Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008)
• Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) <70%

Exclusion Criteria:

• Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1
• Patients with concomitant pulmonary disease
• Patients with a history of asthma
• Any patient with lung cancer or a history of lung cancer
• Patients with a history of certain cardiovascular co-morbid conditions
• Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
• Patients in the active phase of a supervised pulmonary rehabilitation program
• Patients contraindicated for inhaled anticholinergic agents and β2 agonists
• 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
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: indacaterol and glycopyrronium (QVA149); QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.	Drug: indacaterol and glycopyrronium (QVA149); Capsules for inhalation delivered via SDDPI.
ACTIVE_COMPARATOR: glycopyrronium (NVA237); NVA237 50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.	Drug: glycopyrronium (NVA237); Capsules for inhalation delivered via SDDPI.
ACTIVE_COMPARATOR: indacaterol (QAB149); QAB149 150 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.	Drug: indacaterol (QAB149); Capsules for inhalation delivered via SDDPI.
ACTIVE_COMPARATOR: tiotropium; Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.	Drug: tiotropium; Capsules for inhalation delivered via HandiHaler® device.
PLACEBO_COMPARATOR: Placebo; Matching placebo capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDDPI) for 26 weeks. Participants remained on a stable dose of inhaled corticosteroid (ICS) and salbutamol/albuterol was available for use as rescue medication throughout the study.	Drug: placebo; Placebo to match capsules for inhalation delivered via SDDPI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment	Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	23 hours 15 minutes and 23 hour 45 minute post-dose Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transitional Dyspnea Index (TDI) Focal Score at Week 26	A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. A mixed model was used with treatment as a fixed effect with Baseline Dyspnea Index Score and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	Week 26
St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 26	SGRQ is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. A mixed model was used with treatment as a fixed effect with Baseline SGRQ and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	26 weeks
Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Over 26 Weeks	The number of puffs of rescue medication taken in the previous 12 hours was record in patient diary in the morning and in the evening for 26 weeks. The total number of puffs per day was calculated and divided by the number of days with data to determine the mean daily number of puffs of rescue medication for each patient. Rescue medication data recorded during the 14 day run-in was used to calculate the baseline. A negative change from baseline indicates improvement. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	Baseline, Week 26
Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149, QAB149 and NVA237 Compared to Placebo	Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	23 hours 15 minutes and 23 hour 45 minute post-dose Week 26
Trough Forced Expiratory Volume In One Second (FEV1) After 26 Weeks of Treatment With QVA149 Compared to Tiotropium	Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of the 23 hour 15 minute and 23 hour 45 minute post-dose values. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	23 hours 15 minutes and 23 hour 45 minute post-dose Week 26
Baseline Transitional Dyspnea Index (BDI/TDI) Focal Score at Week 12 and Week 26	A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). BDI/TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. A mixed model was used with treatment as a fixed effect with Baseline Dyspnea Index Score and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators as covariates and included baseline smoking status, baseline inhaled corticosteroids and region as fixed effects with center nested within region as a random effect.	Baseline, Week 12, Week 26
Percentage of Patients With a Clinically Important Improvement of at Least 1 Point in TDI Focal Score After 26 Weeks of Treatment	A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing) at Week 12 and Week 26. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. The BDI (baseline) was measured at Day 1. The TDI captures changes from baseline. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9.	Baseline, Week 26
St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 and 26 Weeks of Treatment	SGRQ is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. A mixed model was used with treatment as a fixed effect with Baseline SGRQ and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	Week 12, Week 26
Percentage of Patients With a Clinically Important Improvement From Baseline of at Least 4 Units in the SGRQ Total Score After 26 Weeks of Treatment	SGRQ is a health related quality of life questionnaire consisting of 51 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status.	Baseline, Week 26
Percentage of Nights With "No Night Time Awakenings" Over 26 Weeks	A day with no night time awakenings is defined from the diary data as any day where the patient did not wake up due to COPD symptoms. The percentage of nights is calculated by the number of days with no nighttime awakenings/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline Percent days and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	26 Weeks
Percentage of Days With "No Daytime Symptoms" Over 26 Weeks	A day with no day time symptoms is defined from the diary data as any day where the patient recorded no coughing, no wheezing, no sputum production and no breathlessness during the previous 12 hours (approximately 8AM to 8PM). The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline Percent of days and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	26 Weeks
Percentage of "Days Able to Perform Usual Daily Activities" Over 26 Weeks	Patients answered the question "Did your respiratory symptoms stop you performing your usual activities today?-Not at all in their daily diary. The percentage of days is calculated by the number of days patient is able to perform daily activities/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline Percent of Days and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	26 Weeks
Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication at Week 12 and Week 26	The number of puffs of rescue medication taken in the previous 12 hours was record in patient diary in the morning and in the evening for 26 weeks. The total number of puffs per day was calculated and divided by the number of days with data to determine the mean daily number of puffs of rescue medication for each patient. Rescue medication data recorded during the 14 day run-in was used to calculate the baseline. A negative change from baseline indicates improvement. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	Baseline, Week 12, Week 26
Change From Baseline (BL) in the Daytime and Night Time Rescue Medication Use (Number of Puffs) Over 26 Weeks	The number of puffs of rescue medication taken in the previous 12 hours was record in patient diary in the morning and in the evening for 26 weeks. The total number of puffs in the morning and evening were calculated and divided by the number of days with data to determine the mean daily number of daytime and nighttime puffs. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline (BL) ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	Baseline, Week 26
Percentage of "Days With no Rescue Medication Use" Over 26 Weeks	A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours. The percentage of days is calculated by the number of days with no rescue medicine use/total number of days with evaluable data X 100. A mixed model was used with treatment as a fixed effect with baseline number of puffs and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	26 Weeks
Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours at Day 1 and Week 26	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	From 5 minutes to 4 hours post-dose Day 1 and Week 26
Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours at Day 1 and Week 26	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 8, 12 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	From 5 minutes to 12 hours post-dose Day 1 and Week 26
Standardized FEV1 (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes at Week 26	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 8, 12, 23 hours 15 minutes and 23 hours 45 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. A mixed model was used with treatment as a fixed effect with baseline FEV1 and FEV1 prior to inhalation and FEV1 60 minutes post inhalation of two short acting bronchodilators (components of reversibility at Day -14) as covariates. The model also included baseline smoking status (current/ex-smoker), baseline ICS use (Yes/No) and region as fixed effects with center nested within region as a random effect.	From 5 minutes to 23 hours 45 minutes post-dose Week 26
24 Hour Holter Monitoring in a Subset of Patients	24-hourly mean heart rate was performed using a Holter Monitor at Weeks 12 and 26 in a subgroup of patients. Mixed model: heart rate = treatment + baseline heart rate + baseline smoking status + baseline ICS use + region + center (region) + error. Center was included as a random effect nested within region. The 24-hourly mean heart rate is the mean heart rate over the 24 hour period, derived using hourly mean heart rate beats per minute.	Week 12, Week 26
Rate of Moderate or Severe COPD Exacerbation	Rate of moderate or severe exacerbations per year = total number of moderate or severe exacerbations / total number of treatment years	26 Weeks
Percentage of Patients With at Least One Moderate or Severe COPD Exacerbation Over the 26 Week Treatment Period		26 Weeks
Percentage of Participants With COPD Exacerbations Requiring Hospitalization or Treatment With Systemic Corticosteroids and/or Antibiotics But no Hospitalization		26 Weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Kulich K, Keininger DL, Tiplady B, Banerji D. Symptoms and impact of COPD assessed by an electronic diary in patients with moderate-to-severe COPD: psychometric results from the SHINE study. Int J Chron Obstruct Pulmon Dis. 2015 Jan 7;10:79-94. doi: 10.2147/COPD.S73092. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): February 1, 2012
• Study Completion (ACTUAL): March 1, 2012

Study Registration Dates

• First Submitted: September 13, 2010
• First Submitted That Met QC Criteria: September 13, 2010
• First Posted (ESTIMATE): September 15, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): September 9, 2013
• Last Update Submitted That Met QC Criteria: August 26, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: QVA149, COPD, combination bronchodilator, indacaterol, 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; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Glycopyrrolate; Tiotropium Bromide
• Other Study ID Numbers: CQVA149A2303; 2009-017772-25 (EUDRACT_NUMBER)