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Safety and Efficacy of Indacaterol Once Daily Versus Salmeterol Twice Daily in Chronic Obstructive Pulmonary Disease (COPD) (INSIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00821093
Recruitment Status : Completed
First Posted : January 13, 2009
Results First Posted : August 18, 2011
Last Update Posted : August 18, 2011
Sponsor:
Information provided by:
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease (COPD)
Interventions Drug: Indacaterol 150 µg
Drug: Salmeterol 50 µg
Drug: Placebo to indacaterol
Drug: Placebo to salmeterol
Enrollment 1123
Recruitment Details  
Pre-assignment Details Out of total 1123 randomized patients, two patients withdrew from study prior to exposure to study drug.
Arm/Group Title Indacaterol 150 μg Salmeterol 50 μg
Hide Arm/Group Description Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Period Title: Overall Study
Started 560 563
Exposed to Drug 559 562
Completed 511 523
Not Completed 49 40
Reason Not Completed
Adverse Event             20             12
Withdrawal by Subject             9             13
Lost to Follow-up             9             3
Protocol deviation             3             6
Abnormal laboratory value(s)             2             0
Lack of Efficacy             2             2
Death             2             1
Abnormal test procedure result(s)             1             1
Administrative problems             1             2
Arm/Group Title Indacaterol 150 μg Salmeterol 50 μg Total
Hide Arm/Group Description Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Total of all reporting groups
Overall Number of Baseline Participants 559 562 1121
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 559 participants 562 participants 1121 participants
62.4  (8.86) 63.2  (8.69) 62.8  (8.78)
[1]
Measure Description: Demographic data are based on the safety set of patients.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 559 participants 562 participants 1121 participants
Female
189
  33.8%
147
  26.2%
336
  30.0%
Male
370
  66.2%
415
  73.8%
785
  70.0%
1.Primary Outcome
Title Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 11 Hours 45 Minutes Post-dose at the End of the Study (Week 12, Day 84)
Hide Description FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; 1, 2, 3, 4, and 8 hours; 11 hours 10 minutes and 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates.
Time Frame From 5 minutes to 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).
Arm/Group Title Indacaterol 150 μg Salmeterol 50 μg
Hide Arm/Group Description:
Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Patients inhaled salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Overall Number of Participants Analyzed 504 488
Least Squares Mean (Standard Error)
Unit of Measure: Liters
1.47  (0.009) 1.41  (0.010)
2.Secondary Outcome
Title Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85)
Hide Description FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of treatment. The analysis included baseline FEV1 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates.
Time Frame 24 hours post-dose at the end of the study (Week 12 + 1 day, Day 85)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).
Arm/Group Title Indacaterol 150 μg Salmeterol 50 μg
Hide Arm/Group Description:
Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Patients inhaled salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Overall Number of Participants Analyzed 522 512
Least Squares Mean (Standard Error)
Unit of Measure: Liters
1.41  (0.009) 1.35  (0.010)
Time Frame 12 weeks
Adverse Event Reporting Description The Safety set included all patients who received at least one dose of study drug.
 
Arm/Group Title Indacaterol 150 μg Salmeterol 50 μg
Hide Arm/Group Description Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. Patients inhaled salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
All-Cause Mortality
Indacaterol 150 μg Salmeterol 50 μg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Indacaterol 150 μg Salmeterol 50 μg
Affected / at Risk (%) Affected / at Risk (%)
Total   20/559 (3.58%)   16/562 (2.85%) 
Cardiac disorders     
Acute coronary syndrome  1  0/559 (0.00%)  1/562 (0.18%) 
Acute myocardial infarction  1  1/559 (0.18%)  0/562 (0.00%) 
Angina pectoris  1  2/559 (0.36%)  0/562 (0.00%) 
Atrial fibrillation  1  1/559 (0.18%)  0/562 (0.00%) 
Atrial flutter  1  1/559 (0.18%)  0/562 (0.00%) 
Cardiac failure congestive  1  1/559 (0.18%)  0/562 (0.00%) 
Cardiopulmonary failure  1  1/559 (0.18%)  0/562 (0.00%) 
Coronary artery disease  1  0/559 (0.00%)  1/562 (0.18%) 
Myocardial infarction  1  1/559 (0.18%)  0/562 (0.00%) 
Gastrointestinal disorders     
Abdominal pain upper  1  0/559 (0.00%)  1/562 (0.18%) 
General disorders     
Asthenia  1  0/559 (0.00%)  1/562 (0.18%) 
Pyrexia  1  1/559 (0.18%)  0/562 (0.00%) 
Immune system disorders     
Contrast media allergy  1  0/559 (0.00%)  1/562 (0.18%) 
Infections and infestations     
Bronchitis  1  0/559 (0.00%)  1/562 (0.18%) 
Cellulitis  1  1/559 (0.18%)  0/562 (0.00%) 
Pneumonia  1  1/559 (0.18%)  0/562 (0.00%) 
Upper respiratory tract infection bacterial  1  2/559 (0.36%)  0/562 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  1/559 (0.18%)  0/562 (0.00%) 
Lower limb fracture  1  1/559 (0.18%)  0/562 (0.00%) 
Skin laceration  1  1/559 (0.18%)  0/562 (0.00%) 
Investigations     
Weight decreased  1  1/559 (0.18%)  1/562 (0.18%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  0/559 (0.00%)  1/562 (0.18%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal pain  1  0/559 (0.00%)  1/562 (0.18%) 
Pathological fracture  1  1/559 (0.18%)  0/562 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Gastric cancer  1  1/559 (0.18%)  0/562 (0.00%) 
Lung adenocarcinoma  1  1/559 (0.18%)  0/562 (0.00%) 
Lung neoplasm  1  0/559 (0.00%)  1/562 (0.18%) 
Metastases to spine  1  1/559 (0.18%)  0/562 (0.00%) 
Non-Hodgkin's lymphoma  1  1/559 (0.18%)  0/562 (0.00%) 
Nervous system disorders     
Cerebral infarction  1  1/559 (0.18%)  0/562 (0.00%) 
Cerebrovascular accident  1  1/559 (0.18%)  0/562 (0.00%) 
Hemiparesis  1  1/559 (0.18%)  1/562 (0.18%) 
Ischaemic stroke  1  0/559 (0.00%)  1/562 (0.18%) 
Paraesthesia  1  1/559 (0.18%)  0/562 (0.00%) 
Radicular syndrome  1  0/559 (0.00%)  1/562 (0.18%) 
Spinal cord compression  1  1/559 (0.18%)  0/562 (0.00%) 
Syncope  1  0/559 (0.00%)  1/562 (0.18%) 
Transient ischaemic attack  1  1/559 (0.18%)  0/562 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  4/559 (0.72%)  7/562 (1.25%) 
Respiratory failure  1  0/559 (0.00%)  2/562 (0.36%) 
Vascular disorders     
Peripheral arterial occlusive disease  1  1/559 (0.18%)  0/562 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Indacaterol 150 μg Salmeterol 50 μg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/559 (0.00%)   0/562 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862 778-8300
Layout table for additonal information
Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00821093    
Other Study ID Numbers: CQAB149B2349
2008-005146-23 ( EudraCT Number )
First Submitted: January 9, 2009
First Posted: January 13, 2009
Results First Submitted: July 22, 2011
Results First Posted: August 18, 2011
Last Update Posted: August 18, 2011