Efficacy, Safety, and Tolerability of Once Daily Indacaterol in Chronic Obstructive Pulmonary Disease (COPD) Using Formoterol Twice Daily as Active Control - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Chronic Obstructive Pulmonary Disease
Interventions:	Drug: Indacaterol Drug: Formoterol Drug: Placebo to indacaterol Drug: Placebo to formoterol

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Indacaterol 300 μg Plus Placebo to Formoterol	Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer’s proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.
Indacaterol 600 μg Plus Placebo to Formoterol	Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer’s proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.
Formoterol 12 μg Plus Placebo to Indacaterol	Patients inhaled formoterol 12 μg twice daily via the manufacturer’s proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.
Placebo to Indacaterol Plus Placebo to Formoterol	Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer’s proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.

Participant Flow: Overall Study

	Indacaterol 300 μg Plus Placebo to Formoterol	Indacaterol 600 μg Plus Placebo to Formoterol	Formoterol 12 μg Plus Placebo to Indacaterol	Placebo to Indacaterol Plus Placebo to Formoterol
STARTED	437	428	435	432
Exposed to Study Medication or Placebo	437	425	434	432
COMPLETED	338	326	323	295
NOT COMPLETED	99	102	112	137
Adverse Event	35	24	40	35
Subject withdrew consent	27	40	33	50
Unsatisfactory therapeutic effect	12	9	12	30
Protocol deviation	11	11	11	10
Administrative problems	7	8	5	2
Lost to Follow-up	5	6	5	3
Abnormal laboratory value(s)	1	1	0	0
Death	1	1	5	5
Abnormal test procedure result(s)	0	1	1	2
Subject no longer requires study drug	0	1	0	0

Baseline Characteristics

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Reporting Groups

	Description
Indacaterol 300 μg Plus Placebo to Formoterol	Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer’s proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.
Indacaterol 600 μg Plus Placebo to Formoterol	Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer’s proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.
Formoterol 12 μg Plus Placebo to Indacaterol	Patients inhaled formoterol 12 μg twice daily via the manufacturer’s proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.
Placebo to Indacaterol Plus Placebo to Formoterol	Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer’s proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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	Total of all reporting groups

Baseline Measures

	Indacaterol 300 μg Plus Placebo to Formoterol	Indacaterol 600 μg Plus Placebo to Formoterol	Formoterol 12 μg Plus Placebo to Indacaterol	Placebo to Indacaterol Plus Placebo to Formoterol	Total
Number of Participants [units: participants]	437	425	434	432	1728
Age ^[1] [units: years] Mean ± Standard Deviation	63.9 ± 8.57	62.9 ± 8.74	63.6 ± 8.49	63.2 ± 8.28	63.4 ± 8.52
Gender [units: participants]
Female	86	98	86	80	350
Male	351	327	348	352	1378

[1]	Demographic data are based on all subjects in the safety population, which includes all patients who received at least 1 dose of study drug. Three patients in the indacaterol 600 μg plus placebo to formoterol and one patient in the formoterol 12 μg plus placebo to indacaterol group were not exposed to any study treatment.

Outcome Measures

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1. Primary:

Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85 [ Time Frame: Week 12 + 1 day, Day 85 ]

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2. Secondary:

Percentage of Days of Poor Control During 52 Weeks of Treatment [ Time Frame: Baseline to end of study (Week 52) ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862 778-8300

No publications provided by Novartis

Publications automatically indexed to this study:

Jones PW, Donohue JF, Nedelman J, Pascoe S, Pinault G, Lassen C. Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis. Respir Res. 2011 Dec 29;12:161.

Bleecker ER, Siler T, Owen R, Kramer B. Bronchodilator efficacy and safety of indacaterol 150 ?g once daily in patients with COPD: an analysis of pooled data. Int J Chron Obstruct Pulmon Dis. 2011;6:431-8. Epub 2011 Aug 18.

Jones PW, Mahler DA, Gale R, Owen R, Kramer B. Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respir Med. 2011 Jun;105(6):892-9. Epub 2011 Mar 11.

Worth H, Chung KF, Felser JM, Hu H, Rueegg P. Cardio- and cerebrovascular safety of indacaterol vs formoterol, salmeterol, tiotropium and placebo in COPD. Respir Med. 2011 Apr;105(4):571-9. Epub 2011 Jan 11.

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00393458 History of Changes
Other Study ID Numbers:	CQAB149B2334
Study First Received:	October 25, 2006
Results First Received:	July 22, 2011
Last Updated:	July 22, 2011
Health Authority:	Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Belgium: Federal Agency for Medicinal Products and Health Products Switzerland: Federal Office of Public Health Chile: Instituto de Salud Publica de Chile Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Czech Republic: State Institute for Drug Control Germany: Federal Institute for Drugs and Medical Devices Denmark: Danish Medicines Agency Ecuador: Public Health Ministry Egypt: Ministry of Health and Population Spain: Spanish Agency of Medicines Estonia: The State Agency of Medicine France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) United Kingdom: Medicines and Healthcare Products Regulatory Agency Hungary: National Institute of Pharmacy Israel: Ministry of Health Italy: National Monitoring Centre for Clinical Trials - Ministry of Health Korea: Food and Drug Administration Lithuania: State Medicine Control Agency - Ministry of Health Latvia: State Agency of Medicines Netherlands: Medicines Evaluation Board (MEB) Peru: Ministry of Health Romania: Ministry of Public Health Russia: Ministry of Health of the Russian Federation Slovakia: State Institute for Drug Control Sweden: Medical Products Agency Turkey: Ministry of Health