Trial Outcomes & Findings for Efficacy and Safety of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) Using Salmeterol as Active Control (NCT NCT00567996)

Last Updated: 2011-08-18

Results Overview

Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1002 participants

Primary outcome timeframe

Week 12

Results posted on

2011-08-18

Participant Flow

1002 participants were randomized. 3 randomized participants in the Indacaterol group and 1 randomized participant in the Salmeterol group did not receive study medication and were not included in the intent-to-treat milestone.

Participant milestones

Participant milestones
Measure	Indacaterol 150 μg Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Overall Study STARTED	333	334	335
Overall Study Intent-to-treat: Received Study Drug	330	333	335
Overall Study COMPLETED	289	284	265
Overall Study NOT COMPLETED	44	50	70

Reasons for withdrawal

Reasons for withdrawal
Measure	Indacaterol 150 μg Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Overall Study Adverse Event	18	16	13
Overall Study Protocol Deviation	9	11	13
Overall Study Withdrawal by Subject	8	12	22
Overall Study Abnormal Lab value(s)	2	1	2
Overall Study Abnormal test procedure result(s)	2	1	1
Overall Study Lost to Follow-up	2	5	2
Overall Study Unsatisfactory therapeutic effect	1	2	15
Overall Study Administrative problems	1	1	0
Overall Study Death	1	0	2
Overall Study Patient's inability to use the device	0	1	0

Baseline Characteristics

Efficacy and Safety of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) Using Salmeterol as Active Control

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Indacaterol 150 μg n=330 Participants Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg n=333 Participants Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=335 Participants Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Total n=998 Participants Total of all reporting groups
Age Continuous	63.2 years STANDARD_DEVIATION 8.67 • n=5 Participants	63.4 years STANDARD_DEVIATION 9.19 • n=7 Participants	63.9 years STANDARD_DEVIATION 8.56 • n=5 Participants	63.5 years STANDARD_DEVIATION 8.81 • n=4 Participants
Sex: Female, Male Female	92 Participants n=5 Participants	84 Participants n=7 Participants	77 Participants n=5 Participants	253 Participants n=4 Participants
Sex: Female, Male Male	238 Participants n=5 Participants	249 Participants n=7 Participants	258 Participants n=5 Participants	745 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 12

Population: Intent-to-treat population included all randomized participants who received at least one dose of study medication. The end point was analyzed only for those participants who had Trough FEV1 data at week 12. Missing data were imputed using Last Observation carried Forward (LOCF).

Outcome measures

Outcome measures
Measure	Indacaterol 150 μg n=320 Participants Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg n=317 Participants Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=316 Participants Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment	1.45 Liters Standard Error 0.018	1.39 Liters Standard Error 0.018	1.28 Liters Standard Error 0.019

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-treat population included all randomized participants who received at least one dose of study medication. The endpoint was analyzed only for those participants who had SGRQ data at week 12. Missing data were imputed using Last Observation carried Forward (LOCF).

SGRQ is a health related quality of life questionnaire consisting of 76 items in three sections: symptoms, activity and impacts. The total score is 0 to 100 with a higher score indicating poorer health status. The mixed model used baseline SGRQ total score, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates.

Outcome measures

Outcome measures
Measure	Indacaterol 150 μg n=309 Participants Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg n=301 Participants Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=294 Participants Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 Weeks of Treatment	36.4 Score on a scale Standard Error 1.04	38.5 Score on a scale Standard Error 1.04	42.6 Score on a scale Standard Error 1.05

SECONDARY outcome

Timeframe: Up to 26 weeks

Population: Intent-to-treat population included all randomized participants who received at least one dose of study medication. The endpoint was analyzed only for those participants who had data for this outcome measure.

Participants rated their symptoms on a scale of 0=none to 3=severe. A Chronic Obstructive Pulmonary Disease (COPD) "day of poor control" was defined as any day in the participants diary with a score \>=2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). The mixed model used baseline percentage of "days of poor control", FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates.

Outcome measures

Outcome measures
Measure	Indacaterol 150 μg n=310 Participants Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg n=310 Participants Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=304 Participants Placebo to indacaterol inhaled via SDDPI. Placebo to salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Percentage of COPD "Days of Poor Control" During 26 Weeks of Treatment	34.1 Percentage of days Standard Error 1.82	34.1 Percentage of days Standard Error 1.82	38.1 Percentage of days Standard Error 1.85

Adverse Events

Indacaterol 150 μg

Serious events: 29 serious events

Other events: 69 other events

Deaths: 0 deaths

Salmeterol 50 μg

Serious events: 19 serious events

Other events: 68 other events

Deaths: 0 deaths

Placebo

Serious events: 26 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Indacaterol 150 μg n=330 participants at risk Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Salmeterol 50 μg n=333 participants at risk Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Placebo n=335 participants at risk Placebo to Indacaterol once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.
Infections and infestations Nasopharyngitis	7.3% 24/330 • 26 weeks Safety population consisting of all participants who received at least one dose of study medication.	8.7% 29/333 • 26 weeks Safety population consisting of all participants who received at least one dose of study medication.	6.3% 21/335 • 26 weeks Safety population consisting of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	15.8% 52/330 • 26 weeks Safety population consisting of all participants who received at least one dose of study medication.	14.4% 48/333 • 26 weeks Safety population consisting of all participants who received at least one dose of study medication.	17.3% 58/335 • 26 weeks Safety population consisting of all participants who received at least one dose of study medication.

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 date (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER