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QVA149 Versus Fluticasone/Salmeterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) (ILLUMINATE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01315249
First received: March 11, 2011
Last updated: July 9, 2013
Last verified: July 2013
Results First Received: February 28, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Chronic Obstructive Pulmonary Disease (COPD)
Interventions: Drug: indacaterol and glycopyrronium (QVA149)
Drug: Placebo to fluticasone/salmeterol
Drug: fluticasone/salmeterol
Drug: Placebo to indacaterol and glycopyrronium (QVA149)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
All eligible patients were randomized to one of the 2 arms in a 1:1 ratio for 26 weeks of treatment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 523 patients were randomized. A total of 522 patients (99.8%) were included in the Full analysis Set (FAS) and Safety set. One patient was excluded who was randomized in error and did not receive study medication.

Reporting Groups
  Description
QVA149 Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.
Fluticasone/Salmeterol Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).

Participant Flow:   Overall Study
    QVA149     Fluticasone/Salmeterol  
STARTED     259     264  
COMPLETED     215     217  
NOT COMPLETED     44     47  
Adverse Event                 22                 26  
Withdrawal by Subject                 11                 10  
Protocol Violation                 8                 5  
Abnormal test results                 1                 2  
Administrative problems                 1                 0  
inability to use device                 1                 0  
Lack of Efficacy                 0                 1  
Lost to Follow-up                 0                 2  
Death                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
QVA149 Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.
Fluticasone/Salmeterol Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Total Total of all reporting groups

Baseline Measures
    QVA149     Fluticasone/Salmeterol     Total  
Number of Participants  
[units: participants]
  258     264     522  
Age  
[units: years]
Mean ± Standard Deviation
  63.2  ± 8.16     63.4  ± 7.71     63.3  ± 7.93  
Gender  
[units: participants]
     
Female     77     75     152  
Male     181     189     370  



  Outcome Measures
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1.  Primary:   Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12   [ Time Frame: Week 26 ]

2.  Secondary:   Standardized Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 Hours   [ Time Frame: Week 12 ]

3.  Secondary:   Forced Vital Capacity at All-time Points (Week 12)   [ Time Frame: -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 12 ]

4.  Secondary:   Forced Vital Capacity at All-time Points (Week 26)   [ Time Frame: -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 26 ]

5.  Secondary:   Focal Score of the Transitional Dyspnea Index (TDI)   [ Time Frame: 12 weeks and 26 weeks ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title Focal Score of the Transitional Dyspnea Index (TDI)
Measure Description 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.
Time Frame 12 weeks and 26 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug. FAS were used to analyze all efficacy endpoints, unless otherwise stated. Following the intention-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to.

Reporting Groups
  Description
QVA149 Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.
Fluticasone/Salmeterol Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).

Measured Values
    QVA149     Fluticasone/Salmeterol  
Number of Participants Analyzed  
[units: participants]
  224     236  
Focal Score of the Transitional Dyspnea Index (TDI)  
[units: units on a scale]
Least Squares Mean ± Standard Error
   
12 weeks (n=224 QVA149; 236 flut/salm)     2.03  ± 0.388     1.45  ± 0.374  
26 weeks (n=212 QVA149; 213 flut/salm)     2.36  ± 0.388     1.60  ± 0.376  

No statistical analysis provided for Focal Score of the Transitional Dyspnea Index (TDI)



6.  Secondary:   Total Score of the St. George's Respiratory Questionnaire (SGRQ-C)   [ Time Frame: 12 weeks and 26 weeks ]

7.  Secondary:   Mean Change From Baseline in Daily Number of Puffs of Rescue Medication   [ Time Frame: Baseline, 12 weeks and 26 weeks ]

8.  Secondary:   Change From Baseline in Symptom Scores Reported Using the Ediary   [ Time Frame: 12 weeks and 26 weeks ]

9.  Secondary:   Inspiratory Capacity (IC) at All-time Points (12 Weeks)   [ Time Frame: 12 weeks ]

10.  Secondary:   Inspiratory Capacity (IC) at All-time Points (26 Weeks)   [ Time Frame: 26 weeks ]

11.  Secondary:   Number of Participants With Adverse Events   [ Time Frame: 26 weeks ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
QVA149 Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.
Fluticasone/Salmeterol Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).

Serious Adverse Events
    QVA149     Fluticasone/Salmeterol  
Total, serious adverse events      
# participants affected / at risk     13/258 (5.04%)     14/264 (5.30%)  
Cardiac disorders      
Acute coronary syndrome † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Acute myocardial infarction † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Angina pectoris † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Atrial fibrillation † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Coronary artery stenosis † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Gastrointestinal disorders      
Dyspepsia † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Dysphagia † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Infections and infestations      
Abscess limb † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Bronchitis † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Nasopharyngitis † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Pneumonia † 1    
# participants affected / at risk     0/258 (0.00%)     2/264 (0.76%)  
Injury, poisoning and procedural complications      
Contusion † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Metabolism and nutrition disorders      
Diabetes mellitus † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Musculoskeletal and connective tissue disorders      
Myopathy † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Colon cancer † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Lung adenocarcinoma † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Oesophageal carcinoma † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Rectal cancer † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Small cell lung cancer stage unspecified † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Nervous system disorders      
Carotid artery occlusion † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Carotid artery stenosis † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Ischaemic stroke † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Reproductive system and breast disorders      
Benign prostatic hyperplasia † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Epididymitis † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Respiratory, thoracic and mediastinal disorders      
Acute respiratory failure † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Chronic obstructive pulmonary disease † 1    
# participants affected / at risk     1/258 (0.39%)     3/264 (1.14%)  
Dyspnoea † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Pleural effusion † 1    
# participants affected / at risk     1/258 (0.39%)     1/264 (0.38%)  
Skin and subcutaneous tissue disorders      
Skin ulcer † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Vascular disorders      
Peripheral artery aneurysm † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Venous insufficiency † 1    
# participants affected / at risk     0/258 (0.00%)     1/264 (0.38%)  
Venous thrombosis limb † 1    
# participants affected / at risk     1/258 (0.39%)     0/264 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA




  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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