12-week Efficacy of Indacaterol

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01072448
• Collaborator: (none)
• Enrollment: 323
• Locations: 62
• Arms: 2
• Duration (Months): 5.9
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This 12-week study evaluated the efficacy and safety of indacaterol versus placebo.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Indacaterol 75 μg; Drug: Placebo to indacaterol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 323 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 12-week Treatment, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Once Daily Indacaterol in Patients With Chronic Obstructive Pulmonary Disease
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Indacaterol 75 μg Patients inhaled indacaterol 75 μg once daily in the morning between 8:00 AM 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.	Drug: Indacaterol 75 μg; Indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
Placebo Comparator: Placebo to indacaterol Patients inhaled placebo to indacaterol once daily in the morning between 8:00 AM 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.	Drug: Placebo to indacaterol; Placebo to indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.

Outcome Measures

Primary Outcome Measures

1. Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85) [24 hours post-dose at the end of the study (Week 12 + 1 day, Day 85)]

   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, FEV1 pre-dose and 10-15 minutes post-dose of albuterol during screening, and FEV1 pre-dose and 50-70 minutes post-dose of ipratropium during screening as covariates.

Secondary Outcome Measures

1. Transition Dyspnea Index (TDI) Total Score at the End of the Study (Week 12, Day 84) [End of the study (Week 12, Day 84)]

   An independent (where feasible), trained assessor interviewed the patient and rated the degree of impairment due to dyspnea on a scale from -3 (major deterioration) to 3 (major improvement) on 3 domains (functional impairment, magnitude of task, and magnitude of effort) in comparison with baseline. A total score of the 3 domains ranged from -9 to 9; minus scores indicate deterioration. The analysis included baseline dyspnea index, FEV1 pre-dose and 10-15 minutes post-dose of albuterol during screening, and FEV1 pre-dose and 50-70 minutes post-dose of ipratropium during screening as covariates.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Diagnosis of chronic obstructive pulmonary disease (COPD) (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease [GOLD]

Guidelines, 2008) and:

• Smoking history of at least 10 pack-years

• Post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% of the predicted normal value

• Post-bronchodilator FEV1/FVC (forced vital capacity) < 70%

Exclusion criteria:

• Patients who have had a COPD exacerbation requiring systemic corticosteroids and/or antibiotics and/or hospitalization in the 6 weeks prior to screening

• Patients who have had a respiratory tract infection within 6 weeks prior to screening

• Patients with concomitant pulmonary disease

• Patients with a history of asthma

• Patients with diabetes Type I or uncontrolled diabetes Type II

• Any patient with lung cancer or a history of lung cancer

• Patients with a history of certain cardiovascular co-morbid conditions Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigator Site	Peoria	Arizona	United States	85381
2	Novartis Investigator Site	Pine Bluff	Arkansas	United States	71603
3	Novartis Investigator Site	Buena Park	California	United States	90620
4	Novartis Investigator Site	Encinitas	California	United States	92024
5	Novartis Investigator Site	Fountain Valley	California	United States	92708
6	Novartis Investigator Site	Los Angeles	California	United States	90015
7	Novartis Investigator Site	San Diego	California	United States	92103
8	Novartis Investigator Site	San Diego	California	United States	92120
9	Novartis Investigator Site	Temecula	California	United States	92591
10	Novartis Investigator Site	Torrance	California	United States	90505
11	Novartis Investigator Site	Walnut Creek	California	United States	94598
12	Novartis Investigator Site	Wheat Ridge	Colorado	United States	80033
13	Novartis Investigative Site	Port Orange	Florida	United States	32127
14	Novartis Investigative Site	Sarasota	Florida	United States	34233
15	Novartis Investigative Site	Tamarac	Florida	United States	33321
16	Novartis Investigator Site	Couer D'Alene	Idaho	United States	83814
17	Novartis Investigator Site	Champaign	Illinois	United States	61820
18	Novartis Investigator Site	Downers Grove	Illinois	United States	60515
19	Novartis Investigative Site	River Forest	Illinois	United States	60305
20	Novartis Investigator Site	Skokie	Illinois	United States	60076
21	Novartis Investigator Site	Springfield	Illinois	United States	62703
22	Novartis Investigative site	Lexington	Kentucky	United States	40504
23	Novartis Investigator Site	Covington	Louisiana	United States	70433
24	Novartis Investigator Site	Metaire	Louisiana	United States	70002
25	Novartis Investigative Site	Bangor	Maine	United States	04401
26	Novartis Investigative Site	Columbia	Maryland	United States	21044
27	Novartis Investigative Site	Clarkston	Michigan	United States	48346
28	Novartis Investigative Site	Flint	Michigan	United States	48532
29	Novartis Investigative Site	Livonia	Michigan	United States	48152
30	Novartis Investigative Site	Edina	Minnesota	United States	55435
31	Novartis Investigative Site	Minneapolis	Minnesota	United States	55402
32	Novartis Investigative Site	Plymouth	Minnesota	United States	55441
33	Novartis Investigator Site	Florissant	Missouri	United States	63033
34	Novartis Investigator Site	Ozark	Missouri	United States	65721
35	Novartis Investigator Site	St. Louis	Missouri	United States	63117
36	Novartis Investigative Site	Missoula	Montana	United States	59808
37	Novartis Investigator Site	Bellevue	Nebraska	United States	68123
38	Novartis Investigator Site	Lincoln	Nebraska	United States	68516
39	Novartis Investigator Site	Omaha	Nebraska	United States	68134
40	Novartis Investigator Site	Henderson	Nevada	United States	89014
41	Novartis Investigator Site	Pahrump	Nevada	United States	89048
42	Novartis Investigative Site	New Brunswick	New Jersey	United States	08902
43	Novartis Investigative Site	Ocean	New Jersey	United States	07712
44	Novartis Investigative Site	Rochester	New York	United States	14618
45	Novartis Investigative Site	Charlotte	North Carolina	United States	28209
46	Novartis Investigative Site	Salisbury	North Carolina	United States	28144
47	Novartis Investigative Site	Cincinnati	Ohio	United States	45231
48	Novartis Investigator Site	Medford	Oregon	United States	97504
49	Novartis Investigative Site	Beaver	Pennsylvania	United States	15009
50	Novartis Investigative Site	Erie	Pennsylvania	United States	16506
51	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15221
52	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15243
53	Novartis Investigative Site	Gaffney	South Carolina	United States	29340
54	Novartis Investigative site	Greer	South Carolina	United States	29651
55	Novartis Investigative Site	Seneca	South Carolina	United States	29678
56	Novartis Investigative Site	Johnson City	Tennessee	United States	37601
57	Novartis Investigator Site	Corsicana	Texas	United States	75110
58	Novartis Investigator Site	Fort Worth	Texas	United States	76109
59	Novartis Investigator Site	Salt Lake City	Utah	United States	84107
60	Novartis Investigator Site	Abingdon	Virginia	United States	24210
61	Novartis Investigative Site	Newport News	Virginia	United States	23606
62	Novartis Investigator Site	Tacoma	Washington	United States	98405

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01072448
• Other Study ID Numbers: CQAB149B2354
• First Posted: Feb 22, 2010
• Last Update Posted: Aug 19, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: COPD; indacaterol
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Arm/Group Title	Indacaterol 75 μg	Placebo to Indacaterol
Arm/Group Description	Patients inhaled indacaterol 75 μg once daily in the morning between 8:00 AM 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.	Patients inhaled placebo to indacaterol once daily in the morning between 8:00 AM 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	163	160
COMPLETED	144	130
NOT COMPLETED	19	30

Baseline Characteristics

Arm/Group Title	Indacaterol 75 μg	Placebo to Indacaterol	Total
Arm/Group Description	Patients inhaled indacaterol 75 μg once daily in the morning between 8:00 AM 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.	Patients inhaled placebo to indacaterol once daily in the morning between 8:00 AM 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 Participants	163	160	323
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (8.29)	64.1 (9.43)	64.0 (8.86)
Sex: Female, Male (Count of Participants)
Female	74 45.4%	73 45.6%	147 45.5%
Male	89 54.6%	87 54.4%	176 54.5%

Outcome Measures

1. Primary 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)
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, FEV1 pre-dose and 10-15 minutes post-dose of albuterol during screening, and FEV1 pre-dose and 50-70 minutes post-dose of ipratropium during screening as covariates.
Time Frame	24 hours post-dose at the end of the study (Week 12 + 1 day, Day 85)

Outcome Measure Data

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 75 μg	Placebo to Indacaterol
Arm/Group Description	Patients inhaled indacaterol 75 μg once daily in the morning between 8:00 AM 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.	Patients inhaled placebo to indacaterol once daily in the morning between 8:00 AM 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.
Measure Participants	149	148
Least Squares Mean (Standard Error) [Liters]	1.38 (0.013)	1.26 (0.013)

2. Secondary Outcome

Title	Transition Dyspnea Index (TDI) Total Score at the End of the Study (Week 12, Day 84)
Description	An independent (where feasible), trained assessor interviewed the patient and rated the degree of impairment due to dyspnea on a scale from -3 (major deterioration) to 3 (major improvement) on 3 domains (functional impairment, magnitude of task, and magnitude of effort) in comparison with baseline. A total score of the 3 domains ranged from -9 to 9; minus scores indicate deterioration. The analysis included baseline dyspnea index, FEV1 pre-dose and 10-15 minutes post-dose of albuterol during screening, and FEV1 pre-dose and 50-70 minutes post-dose of ipratropium during screening as covariates.
Time Frame	End of the study (Week 12, Day 84)

Outcome Measure Data

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 75 μg	Placebo to Indacaterol
Arm/Group Description	Patients inhaled indacaterol 75 μg once daily in the morning between 8:00 AM 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.	Patients inhaled placebo to indacaterol once daily in the morning between 8:00 AM 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.
Measure Participants	150	150
Least Squares Mean (Standard Error) [Units on a scale]	1.34 (0.284)	0.11 (0.287)

Adverse Events

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 75 μg		Placebo to Indacaterol
Arm/Group Description	Patients inhaled indacaterol 75 μg once daily in the morning between 8:00 AM 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.		Patients inhaled placebo to indacaterol once daily in the morning between 8:00 AM 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 75 μg		Placebo to Indacaterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Indacaterol 75 μg		Placebo to Indacaterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/163 (2.5%)		9/160 (5.6%)
Blood and lymphatic system disorders
Anaemia	1/163 (0.6%)		0/160 (0%)
Lymphadenopathy	0/163 (0%)		1/160 (0.6%)
Cardiac disorders
Myocardial infarction	0/163 (0%)		1/160 (0.6%)
General disorders
Non-cardiac chest pain	1/163 (0.6%)		0/160 (0%)
Infections and infestations
Pneumonia	0/163 (0%)		2/160 (1.3%)
Sinusitis	0/163 (0%)		1/160 (0.6%)
Upper respiratory tract infection bacterial	0/163 (0%)		1/160 (0.6%)
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	0/163 (0%)		1/160 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mycosis fungoides	1/163 (0.6%)		0/160 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/163 (0.6%)		4/160 (2.5%)
Pulmonary mass	0/163 (0%)		1/160 (0.6%)
Vascular disorders
Aortic aneurysm rupture	0/163 (0%)		1/160 (0.6%)
Other (Not Including Serious) Adverse Events
	Indacaterol 75 μg		Placebo to Indacaterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/163 (17.8%)		23/160 (14.4%)
Infections and infestations
Urinary tract infection	9/163 (5.5%)		2/160 (1.3%)
Nervous system disorders
Headache	9/163 (5.5%)		6/160 (3.8%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	14/163 (8.6%)		15/160 (9.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.