Comparison of Efficacy of Indacaterol Versus Placebo Over 12 Weeks

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01068600
• Collaborator: (none)
• Enrollment: 318
• Locations: 54
• Arms: 2
• Patients Per Site: 5.9

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; Drug: Placebo to indacaterol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 318 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: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Indacaterol; Once daily via single-dose dry powder inhaler (SDDPI)
Placebo Comparator: 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.	Drug: Placebo to indacaterol; Once daily via SDDPI

Outcome Measures

Primary Outcome Measures

1. Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment [after 12 weeks]

   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.

Secondary Outcome Measures

1. Transition Dyspnoea Index (TDI) Focal Score After 12 Weeks of Treatment [after 12 weeks]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for

Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008) and:

1. Smoking history of at least 10 pack-years

2. Post-bronchodilator FEV1 <80% and ≥30% of the predicted normal value

3. 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 for 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 comorbid conditions

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Anniston	Alabama	United States	36207-5710
2	Novartis Investigative Site	Jasper	Alabama	United States	35501
3	Novartis Investigator Site	Glendale	Arizona	United States	85306
4	Novartis Investigator Site	Phoenix	Arizona	United States	85006
5	Novartis Investigator Site	Fullerton	California	United States	92835
6	Novartis Investigator Site	Los Angeles	California	United States	90048
7	Novartis Investigator Site	Los Angeles	California	United States	90095
8	Novartis Investigator Site	Riverside	California	United States	92506
9	Novartis Investigative Site	Clearwater	Florida	United States	33756
10	Novartis Investigative Site	Clearwater	Florida	United States	33765
11	Novartis Investigative Site	Hollywood	Florida	United States	33021
12	Novartis Investigative site	Miami	Florida	United States	33145
13	Novartis Investigative Site	Tampa	Florida	United States	33603
14	Novartis Investigative Site	Winter Park	Florida	United States	32789
15	Novartis Investigative Site	Atlanta	Georgia	United States	30342
16	Novartis Investigator Site	Normal	Illinois	United States	61761
17	Novartis Investigator Site	Iowa City	Iowa	United States	52242
18	Novartis Investigative Site	Madisonville	Kentucky	United States	42431
19	Novartis Investigator Site	Baton Rouge	Louisiana	United States	70808
20	Novartis Investigator Site	Opelousas	Louisiana	United States	70570
21	Novartis Investigator Site	St. Charles	Missouri	United States	63301
22	Novartis Investigator Site	St. Louis	Missouri	United States	63141
23	Novartis Investigator Site	Lincoln	Nebraska	United States	68510
24	Novartis Investigator Site	Omaha	Nebraska	United States	68114
25	Novartis Investigator Site	Omaha	Nebraska	United States	68134
26	Novartis Investigator Site	Henderson	Nevada	United States	89014
27	Novartis Investigator Site	Las Vegas	Nevada	United States	89119
28	Novartis Investigative Site	Cherry Hill	New Jersey	United States	08003
29	Novartis Investigator Site	Albuquerque	New Mexico	United States	87108
30	Novartis Investigative Site	Charlotte	North Carolina	United States	28207
31	Novartis Investigative Site	Raleigh	North Carolina	United States	27607
32	Novartis Investigative Site	Shelby	North Carolina	United States	28152
33	Novartis Investigative Site	Canton	Ohio	United States	44718
34	Novartis Investigator Site	Cincinnati	Ohio	United States	45242
35	Novartis Investigative Site	Columbus	Ohio	United States	43213
36	Novartis Investigative Site	Columbus	Ohio	United States	43215
37	Novartis Investigator Site	Marion	Ohio	United States	43302
38	Novartis Investigator Site	Eugene	Oregon	United States	97404
39	Novartis Investigator Site	Medford	Oregon	United States	97504
40	Novartis Investigative Site	Cumberland	Rhode Island	United States	02864
41	Novartis Investigative Site	Pawtucket	Rhode Island	United States	02860
42	Novartis Investigative Site	Charleston	South Carolina	United States	29407
43	Novartis Investigative Site	Charleston	South Carolina	United States	29412
44	Novartis Investigative Site	Easley	South Carolina	United States	29640
45	Novartis Investigative site	Greenville	South Carolina	United States	29615
46	Novartis Investigative Site	North Charleston	South Carolina	United States	29406
47	Novartis Investigative Site	Spartanburg	South Carolina	United States	29303
48	Novartis Investigative Site	Union	South Carolina	United States	29379
49	Novartis Investigator Site	Arlington	Texas	United States	76012
50	Novartis Investigator Site	Dickinson	Texas	United States	77539
51	Novartis Investigator Site	El Paso	Texas	United States	79903
52	Novartis Investigator Site	McKinney	Texas	United States	75069
53	Novartis Investigative Site	South Burlington	Vermont	United States	05403
54	Novartis Investigative Site	Richmond	Virginia	United States	23229

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: NCT01068600
• Other Study ID Numbers: CQAB149B2355
• First Posted: Feb 15, 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
Arm/Group Description	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 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.
Period Title: Overall Study
STARTED	159	159
COMPLETED	148	142
NOT COMPLETED	11	17

Baseline Characteristics

Arm/Group Title	Indacaterol 75 µg	Placebo	Total
Arm/Group Description	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 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 of all reporting groups
Overall Participants	159	159	318
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.3 (9.83)	61.5 (9.85)	61.4 (9.83)
Sex: Female, Male (Count of Participants)
Female	76 47.8%	70 44%	146 45.9%
Male	83 52.2%	89 56%	172 54.1%

Outcome Measures

1. Primary Outcome

Title	Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment
Description	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.
Time Frame	after 12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Indacaterol 75 µg	Placebo
Arm/Group Description	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 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.
Measure Participants	145	150
Least Squares Mean (Standard Error) [Liters]	1.49 (0.016)	1.35 (0.015)

2. Secondary Outcome

Title	Transition Dyspnoea Index (TDI) Focal Score After 12 Weeks of Treatment
Description	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.
Time Frame	after 12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Indacaterol 75 µg	Placebo
Arm/Group Description	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 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.
Measure Participants	148	149
Least Squares Mean (Standard Error) [Score on a scale]	1.22 (0.234)	0.76 (0.235)

Adverse Events

Adverse Event Reporting Description	Safety set included all randomized participants who received study drug.
Arm/Group Title	Indacaterol 75 µg		Placebo
Arm/Group Description	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 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.
All Cause Mortality
	Indacaterol 75 µg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Indacaterol 75 µg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/159 (2.5%)		4/159 (2.5%)
Blood and lymphatic system disorders
Splenic infarction	0/159 (0%)		1/159 (0.6%)
Eye disorders
Visual impairment	0/159 (0%)		1/159 (0.6%)
General disorders
Non-cardiac chest pain	1/159 (0.6%)		0/159 (0%)
Infections and infestations
Bronchitis	1/159 (0.6%)		0/159 (0%)
Pneumonia	1/159 (0.6%)		0/159 (0%)
Injury, poisoning and procedural complications
Limb crushing injury	0/159 (0%)		1/159 (0.6%)
Metabolism and nutrition disorders
Dehydration	0/159 (0%)		1/159 (0.6%)
Nervous system disorders
Cerebrovascular accident	1/159 (0.6%)		0/159 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/159 (0.6%)		0/159 (0%)
Haemoptysis	1/159 (0.6%)		0/159 (0%)
Other (Not Including Serious) Adverse Events
	Indacaterol 75 µg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/159 (36.5%)		46/159 (28.9%)
Cardiac disorders
Supraventricular extrasystoles	2/159 (1.3%)		0/159 (0%)
Ear and labyrinth disorders
Ear pain	2/159 (1.3%)		0/159 (0%)
Eye disorders
Vision blurred	0/159 (0%)		2/159 (1.3%)
Gastrointestinal disorders
Abdominal pain upper	0/159 (0%)		2/159 (1.3%)
Diarrhoea	1/159 (0.6%)		3/159 (1.9%)
Gastrooesophageal reflux disease	0/159 (0%)		2/159 (1.3%)
Vomiting	2/159 (1.3%)		0/159 (0%)
General disorders
Oedema peripheral	2/159 (1.3%)		1/159 (0.6%)
Immune system disorders
Seasonal allergy	2/159 (1.3%)		0/159 (0%)
Infections and infestations
Bronchitis	4/159 (2.5%)		2/159 (1.3%)
Lower respiratory tract infection	0/159 (0%)		2/159 (1.3%)
Nasopharyngitis	10/159 (6.3%)		3/159 (1.9%)
Pneumonia	2/159 (1.3%)		2/159 (1.3%)
Sinusitis	1/159 (0.6%)		6/159 (3.8%)
Upper respiratory tract infection	5/159 (3.1%)		6/159 (3.8%)
Upper respiratory tract infection bacterial	3/159 (1.9%)		2/159 (1.3%)
Urinary tract infection	1/159 (0.6%)		4/159 (2.5%)
Viral upper respiratory tract infection	2/159 (1.3%)		0/159 (0%)
Injury, poisoning and procedural complications
Contusion	1/159 (0.6%)		2/159 (1.3%)
Investigations
Blood creatine phosphokinase increased	1/159 (0.6%)		3/159 (1.9%)
C-reactive protein increased	1/159 (0.6%)		2/159 (1.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/159 (0.6%)		2/159 (1.3%)
Muscle spasms	3/159 (1.9%)		0/159 (0%)
Pain in extremity	0/159 (0%)		2/159 (1.3%)
Nervous system disorders
Headache	5/159 (3.1%)		2/159 (1.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	13/159 (8.2%)		13/159 (8.2%)
Cough	15/159 (9.4%)		5/159 (3.1%)
Dyspnoea	0/159 (0%)		2/159 (1.3%)
Epistaxis	2/159 (1.3%)		0/159 (0%)
Oropharyngeal pain	6/159 (3.8%)		2/159 (1.3%)
Vascular disorders
Hypertension	4/159 (2.5%)		2/159 (1.3%)

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 (i.e., data from all sites) in the clinical trial.