Efficacy and Safety of Different Doses of Indacaterol in Chronic Obstructive Pulmonary Disease (COPD)

A Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Different Doses of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease, Using Salmeterol as an Active Control

This study compared the 14-day bronchodilator efficacy of indacaterol with that of placebo and salmeterol.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Indacaterol; Drug: Placebo to salmeterol; Drug: Salmeterol 50 μg; Drug: Placebo to indacaterol

• Study Type: Interventional
• Enrollment (Actual): 552
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Florence, Alabama, United States, 35630
      • Novartis Investigator Site
    • Jasper, Alabama, United States, 35501
      • Novartis Investigator Site
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Novartis Investigator Site
  • Arkansas
    • Searcy, Arkansas, United States, 72143
      • Novartis Investigator Site
  • California
    • Fullerton, California, United States, 92835
      • Novartis Investigator Site
    • Rancho Mirage, California, United States, 92270
      • Novartis Investigative Site
    • Riverside, California, United States, 92506
      • Novartis Investigator Site
    • San Diego, California, United States, 92120
      • Novartis Investigator Site
    • Stockton, California, United States, 95207
      • Novartis Investigator Site
    • Temecula, California, United States, 92591
      • Novartis Investigator Site
    • Walnut Creek, California, United States, 94598
      • Novartis Investigator Site
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Novartis Investigator Site
  • Connecticut
    • Glastonbury, Connecticut, United States, 06033
      • Novartis Investigative Site
    • Stamford, Connecticut, United States, 06902
      • Novartis Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Novartis Investigator Site
    • Defuniak Springs, Florida, United States, 32435
      • Novartis Investigator Site
    • Hollywood, Florida, United States, 33021
      • Novartis Investigative Site
    • Miami, Florida, United States, 33145
      • Novartis Investigator Site
    • Pensacola, Florida, United States, 32503
      • Novartis Investigative Site
    • Pensacola, Florida, United States, 32504
      • Novartis Investigative Site
    • Tamarac, Florida, United States, 33321
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33603
      • Novartis Investigator Site
  • Illinois
    • O'Fallon, Illinois, United States, 62269
      • Novartis Investigator Site
  • Kentucky
    • Florence, Kentucky, United States, 41017
      • Novartis Investigator Site
    • Madisonville, Kentucky, United States, 42431
      • Novartis Investigator Site
  • Louisiana
    • Opelousas, Louisiana, United States, 70570
      • Novartis Investigator Site
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Novartis Investigative Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Novartis Investigator Site
    • Fridley, Minnesota, United States, 55432
      • Novartis Investigator Site
    • Minneapolis, Minnesota, United States, 55402
      • Novartis Investigator Site
  • Missouri
    • Ozark, Missouri, United States, 65721
      • Novartis Investigator Site
    • St. Louis, Missouri, United States, 63141
      • Novartis Investigator Site
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Novartis Investigator Site
    • Lincoln, Nebraska, United States, 68510
      • Novartis Investigator Site
    • Omaha, Nebraska, United States, 68134
      • Novartis Investigator Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Novartis Investigator Site
    • Las Vegas, Nevada, United States, 89119
      • Novartis Investigator Site
    • Las Vegas, Nevada, United States, 89183
      • Novartis Investigator Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Novartis Investigator Site
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08003
      • Novartis Investigative Site
  • New York
    • Bayside, New York, United States, 11361
      • Novartis Investigative Site
    • Great Neck, New York, United States, 11023
      • Novartis Investigative Site
    • Lake Success, New York, United States, 11042
      • Novartis Investigative Site
    • Larchmont, New York, United States, 10538
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Novartis Investigative Site
    • Shelby, North Carolina, United States, 28152
      • Novartis Investigative Site
  • Ohio
    • Cadiz, Ohio, United States, 43907
      • Novartis Investigator Site
    • Canton, Ohio, United States, 44718
      • Novartis Investigator Site
    • Columbus, Ohio, United States, 43215
      • Novartis Investigator Site
    • Toledo, Ohio, United States, 43608
      • Novartis Investigator Site
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Novartis Investigative Site
    • Medford, Oregon, United States, 97504
      • Novartis Investigator Site
  • Pennsylvania
    • Phoenixville, Pennsylvania, United States, 19460
      • Novartis Investigative Site
    • Pittsburgh, Pennsylvania, United States, 15243
      • Novartis Investigative Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Novartis Investigative Site
    • Charleston, South Carolina, United States, 29406-7108
      • Novartis Investigative Site
    • Easley, South Carolina, United States, 29640
      • Novartis Investigative Site
    • Greenville, South Carolina, United States, 29615
      • Novartis Investigative Site
    • Spartanburg, South Carolina, United States, 29303
      • Novartis Investigative Site
    • Union, South Carolina, United States, 29379
      • Novartis Investigative Site
  • Tennessee
    • Cookeville, Tennessee, United States, 38501
      • Novartis Investigator Site
  • Texas
    • Dickinson, Texas, United States, 77539
      • Novartis Investigator Site
    • Ft. Worth, Texas, United States, 76104
      • Novartis Investigator Site
    • McKinney, Texas, United States, 75069
      • Novartis Investigator Site
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Novartis Investigator Site
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Novartis Investigative Site
    • Newport News, Virginia, United States, 23606
      • Novartis Investigative Site
    • Richmond, Virginia, United States, 23229
      • Novartis Investigative Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Smoking history of at least 10 pack-years
  2. Post-bronchodilator forced expiratory volume in 1 second (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 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 applied to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indacaterol 18.75 μg; Patients inhaled indacaterol 18.75 μg once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.; Drug: Placebo to salmeterol; Placebo to salmeterol was supplied in the manufacturer's proprietary Diskus inhaler device.
Experimental: Indacaterol 37.5 μg; Patients inhaled indacaterol 37.5 μg once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.; Drug: Placebo to salmeterol; Placebo to salmeterol was supplied in the manufacturer's proprietary Diskus inhaler device.
Experimental: Indacaterol 75 μg; Patients inhaled indacaterol 75 μg once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.; Drug: Placebo to salmeterol; Placebo to salmeterol was supplied in the manufacturer's proprietary Diskus inhaler device.
Experimental: Indacaterol 150 μg; Patients inhaled indacaterol 150 μg once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.; Drug: Placebo to salmeterol; Placebo to salmeterol was supplied in the manufacturer's proprietary Diskus inhaler device.
Active Comparator: Salmeterol 50 μg; Patients inhaled salmeterol 50 μg twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. In addition, patients inhaled placebo to indacaterol once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study.	Drug: Salmeterol 50 μg; Salmeterol was supplied in the manufacturer's proprietary Diskus inhaler device.; Drug: Placebo to indacaterol; Placebo to indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
Placebo Comparator: Placebo; Patients inhaled placebo to indacaterol once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study.	Drug: Placebo to salmeterol; Placebo to salmeterol was supplied in the manufacturer's proprietary Diskus inhaler device.; Drug: Placebo to indacaterol; Placebo to indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 2 + 1 Day, Day 15)	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 salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	24 hours post-dose at the end of the study (Week 2 + 1 day, Day 15)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2	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 on Day 2. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	24 hours post-dose on Day 2

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: March 17, 2010
• First Submitted That Met QC Criteria: March 17, 2010
• First Posted (Estimate): March 18, 2010

Study Record Updates

• Last Update Posted (Estimate): August 19, 2011
• Last Update Submitted That Met QC Criteria: July 22, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: COPD; salmeterol; Indacaterol
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Salmeterol Xinafoate
• Other Study ID Numbers: CQAB149B2356