Trial Outcomes & Findings for Safety and Efficacy of Indacaterol Once Daily Versus Salmeterol Twice Daily in Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00821093)

Last Updated: 2011-08-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1123 participants

Primary outcome timeframe

From 5 minutes to 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84)

Results posted on

2011-08-18

Participant Flow

Out of total 1123 randomized patients, two patients withdrew from study prior to exposure to study drug.

Participant milestones

Participant milestones
Measure	Indacaterol 150 μg 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.	Salmeterol 50 μg 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 Study STARTED	560	563
Overall Study Exposed to Drug	559	562
Overall Study COMPLETED	511	523
Overall Study NOT COMPLETED	49	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Indacaterol 150 μg 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.	Salmeterol 50 μg 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 Study Adverse Event	20	12
Overall Study Withdrawal by Subject	9	13
Overall Study Lost to Follow-up	9	3
Overall Study Protocol deviation	3	6
Overall Study Abnormal laboratory value(s)	2	0
Overall Study Lack of Efficacy	2	2
Overall Study Death	2	1
Overall Study Abnormal test procedure result(s)	1	1
Overall Study Administrative problems	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Indacaterol 150 μg n=559 Participants 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.	Salmeterol 50 μg n=562 Participants 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 n=1121 Participants Total of all reporting groups
Age Continuous	62.4 years STANDARD_DEVIATION 8.86 • n=5 Participants	63.2 years STANDARD_DEVIATION 8.69 • n=7 Participants	62.8 years STANDARD_DEVIATION 8.78 • n=5 Participants
Sex: Female, Male Female	189 Participants n=5 Participants	147 Participants n=7 Participants	336 Participants n=5 Participants
Sex: Female, Male Male	370 Participants n=5 Participants	415 Participants n=7 Participants	785 Participants n=5 Participants

PRIMARY outcome

Timeframe: From 5 minutes to 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84)

Population: Full analysis set: All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Indacaterol 150 μg n=504 Participants 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.	Salmeterol 50 μg n=488 Participants 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.
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)	1.47 Liters Standard Error 0.009	1.41 Liters Standard Error 0.010

SECONDARY outcome

Timeframe: 24 hours post-dose at the end of the study (Week 12 + 1 day, Day 85)

Population: Full analysis set: All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

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.

Outcome measures

Outcome measures
Measure	Indacaterol 150 μg n=522 Participants 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.	Salmeterol 50 μg n=512 Participants 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.
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85)	1.41 Liters Standard Error 0.009	1.35 Liters Standard Error 0.010

Adverse Events

Indacaterol 150 μg

Serious events: 20 serious events

Other events: 0 other events

Deaths: 0 deaths

Salmeterol 50 μg

Serious events: 16 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Indacaterol 150 μg n=559 participants at risk 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.	Salmeterol 50 μg n=562 participants at risk 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.
Cardiac disorders Acute coronary syndrome	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Cardiac disorders Acute myocardial infarction	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Cardiac disorders Angina pectoris	0.36% 2/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Cardiac disorders Atrial flutter	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Cardiac disorders Cardiac failure congestive	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Cardiac disorders Cardiopulmonary failure	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Cardiac disorders Coronary artery disease	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
General disorders Asthenia	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
General disorders Pyrexia	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Immune system disorders Contrast media allergy	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Infections and infestations Bronchitis	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Infections and infestations Cellulitis	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Infections and infestations Pneumonia	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection bacterial	0.36% 2/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Injury, poisoning and procedural complications Lower limb fracture	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Injury, poisoning and procedural complications Skin laceration	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Investigations Weight decreased	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pathological fracture	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Nervous system disorders Cerebral infarction	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Nervous system disorders Cerebrovascular accident	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Nervous system disorders Hemiparesis	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Nervous system disorders Ischaemic stroke	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Nervous system disorders Paraesthesia	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Nervous system disorders Radicular syndrome	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Nervous system disorders Spinal cord compression	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Nervous system disorders Syncope	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.18% 1/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Nervous system disorders Transient ischaemic attack	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.72% 4/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	1.2% 7/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.36% 2/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.
Vascular disorders Peripheral arterial occlusive disease	0.18% 1/559 • 12 weeks The Safety set included all patients who received at least one dose of study drug.	0.00% 0/562 • 12 weeks The Safety set included all patients who received at least one dose of study drug.