Trial Outcomes & Findings for Comparison of Efficacy of Indacaterol Versus Placebo Over 12 Weeks (NCT NCT01068600)

Last Updated: 2011-08-19

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 albuterol, and FEV1 prior to and 50-70 minutes post inhalation of ipratropium as covariates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

318 participants

Primary outcome timeframe

after 12 weeks

Results posted on

2011-08-19

Participant Flow

Participant milestones

Participant milestones
Measure	Indacaterol 75 µg Indacaterol 75 µg inhaled once daily in the morning via Concept1, a single dose dry powder inhaler (SDDPI), for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.	Placebo Placebo to indacaterol inhaled once daily in the morning via Concept1, a SDDPI, for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.
Overall Study STARTED	159	159
Overall Study COMPLETED	148	142
Overall Study NOT COMPLETED	11	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Indacaterol 75 µg Indacaterol 75 µg inhaled once daily in the morning via Concept1, a single dose dry powder inhaler (SDDPI), for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.	Placebo Placebo to indacaterol inhaled once daily in the morning via Concept1, a SDDPI, for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.
Overall Study Withdrawal by Subject	5	6
Overall Study Adverse Event	3	3
Overall Study Abnormal laboratory value(s)	1	0
Overall Study Lost to Follow-up	1	2
Overall Study Protocol deviation	1	1
Overall Study Unsatisfactory therapeutic effect	0	4
Overall Study Administrative problems	0	1

Baseline Characteristics

Comparison of Efficacy of Indacaterol Versus Placebo Over 12 Weeks

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Indacaterol 75 µg n=159 Participants Indacaterol 75 µg inhaled once daily in the morning via Concept1, a single dose dry powder inhaler (SDDPI), for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.	Placebo n=159 Participants Placebo to indacaterol inhaled once daily in the morning via Concept1, a SDDPI, for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.	Total n=318 Participants Total of all reporting groups
Age Continuous	61.3 years STANDARD_DEVIATION 9.83 • n=5 Participants	61.5 years STANDARD_DEVIATION 9.85 • n=7 Participants	61.4 years STANDARD_DEVIATION 9.83 • n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	70 Participants n=7 Participants	146 Participants n=5 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	89 Participants n=7 Participants	172 Participants n=5 Participants

PRIMARY outcome

Timeframe: after 12 weeks

Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. The endpoint was analyzed only for those participants who had data for this outcome measure. Missing data was imputed using last observation carried forward.

Outcome measures

Outcome measures
Measure	Indacaterol 75 µg n=145 Participants Indacaterol 75 µg inhaled once daily in the morning via Concept1, a single dose dry powder inhaler (SDDPI), for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.	Placebo n=150 Participants Placebo to indacaterol inhaled once daily in the morning via Concept1, a SDDPI, for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.
Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment	1.49 Liters Standard Error 0.016	1.35 Liters Standard Error 0.015

SECONDARY outcome

Timeframe: after 12 weeks

Population: Full Analysis Set included all randomized participants who received at least one dose of study medication. If data were missing or insufficient for any one of the domains a focal score was not calculated. Missing focal scores after week 4 were imputed using last observation carried forward.

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 with a negative score indicating a deterioration from baseline. A 1 unit difference in the TDI focal score is clinically significant. Mixed model used baseline dyspnoea index, FEV1 prior to and 10-15 minutes post inhalation of albuterol, and FEV1 prior to and 50-70 minutes post inhalation of ipratropium as covariates.

Outcome measures

Outcome measures
Measure	Indacaterol 75 µg n=148 Participants Indacaterol 75 µg inhaled once daily in the morning via Concept1, a single dose dry powder inhaler (SDDPI), for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.	Placebo n=149 Participants Placebo to indacaterol inhaled once daily in the morning via Concept1, a SDDPI, for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.
Transition Dyspnoea Index (TDI) Focal Score After 12 Weeks of Treatment	1.22 Score on a scale Standard Error 0.234	0.76 Score on a scale Standard Error 0.235

Adverse Events

Indacaterol 75 µg

Serious events: 4 serious events

Other events: 58 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Indacaterol 75 µg n=159 participants at risk Indacaterol 75 µg inhaled once daily in the morning via Concept1, a single dose dry powder inhaler (SDDPI), for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.	Placebo n=159 participants at risk Placebo to indacaterol inhaled once daily in the morning via Concept1, a SDDPI, for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.
Blood and lymphatic system disorders Splenic infarction	0.00% 0/159 Safety set included all randomized participants who received study drug.	0.63% 1/159 Safety set included all randomized participants who received study drug.
Eye disorders Visual impairment	0.00% 0/159 Safety set included all randomized participants who received study drug.	0.63% 1/159 Safety set included all randomized participants who received study drug.
General disorders Non-cardiac chest pain	0.63% 1/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Infections and infestations Bronchitis	0.63% 1/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Infections and infestations Pneumonia	0.63% 1/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Injury, poisoning and procedural complications Limb crushing injury	0.00% 0/159 Safety set included all randomized participants who received study drug.	0.63% 1/159 Safety set included all randomized participants who received study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/159 Safety set included all randomized participants who received study drug.	0.63% 1/159 Safety set included all randomized participants who received study drug.
Nervous system disorders Cerebrovascular accident	0.63% 1/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.63% 1/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.63% 1/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.

Other adverse events

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

Restriction type: OTHER

Measure	Indacaterol 75 µg n=159 participants at risk Indacaterol 75 µg inhaled once daily in the morning via Concept1, a single dose dry powder inhaler (SDDPI), for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.	Placebo n=159 participants at risk Placebo to indacaterol inhaled once daily in the morning via Concept1, a SDDPI, for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study.
Cardiac disorders Supraventricular extrasystoles	1.3% 2/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Ear and labyrinth disorders Ear pain	1.3% 2/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Eye disorders Vision blurred	0.00% 0/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Gastrointestinal disorders Diarrhoea	0.63% 1/159 Safety set included all randomized participants who received study drug.	1.9% 3/159 Safety set included all randomized participants who received study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Gastrointestinal disorders Vomiting	1.3% 2/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
General disorders Oedema peripheral	1.3% 2/159 Safety set included all randomized participants who received study drug.	0.63% 1/159 Safety set included all randomized participants who received study drug.
Immune system disorders Seasonal allergy	1.3% 2/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Infections and infestations Bronchitis	2.5% 4/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Infections and infestations Lower respiratory tract infection	0.00% 0/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Infections and infestations Nasopharyngitis	6.3% 10/159 Safety set included all randomized participants who received study drug.	1.9% 3/159 Safety set included all randomized participants who received study drug.
Infections and infestations Pneumonia	1.3% 2/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Infections and infestations Sinusitis	0.63% 1/159 Safety set included all randomized participants who received study drug.	3.8% 6/159 Safety set included all randomized participants who received study drug.
Infections and infestations Upper respiratory tract infection	3.1% 5/159 Safety set included all randomized participants who received study drug.	3.8% 6/159 Safety set included all randomized participants who received study drug.
Infections and infestations Upper respiratory tract infection bacterial	1.9% 3/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Infections and infestations Urinary tract infection	0.63% 1/159 Safety set included all randomized participants who received study drug.	2.5% 4/159 Safety set included all randomized participants who received study drug.
Infections and infestations Viral upper respiratory tract infection	1.3% 2/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Injury, poisoning and procedural complications Contusion	0.63% 1/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Investigations Blood creatine phosphokinase increased	0.63% 1/159 Safety set included all randomized participants who received study drug.	1.9% 3/159 Safety set included all randomized participants who received study drug.
Investigations C-reactive protein increased	0.63% 1/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Musculoskeletal and connective tissue disorders Back pain	0.63% 1/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	1.9% 3/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Nervous system disorders Headache	3.1% 5/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	8.2% 13/159 Safety set included all randomized participants who received study drug.	8.2% 13/159 Safety set included all randomized participants who received study drug.
Respiratory, thoracic and mediastinal disorders Cough	9.4% 15/159 Safety set included all randomized participants who received study drug.	3.1% 5/159 Safety set included all randomized participants who received study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.3% 2/159 Safety set included all randomized participants who received study drug.	0.00% 0/159 Safety set included all randomized participants who received study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.8% 6/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.
Vascular disorders Hypertension	2.5% 4/159 Safety set included all randomized participants who received study drug.	1.3% 2/159 Safety set included all randomized participants who received study drug.