A Crossover Study to Determine the 24 Hour Lung Function Profile of Indacaterol in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, 3-period, 14-day Crossover Study to Determine the 24 Hour Lung Function Profile of Indacaterol (300 µg Once Daily [od]) in Patients With Moderate-to-severe COPD, Using Open-label Salmeterol (50 µg Twice Daily [Bis in Die, Bid]) as Active Control

This study was conducted to provide detailed information on the efficacy of indacaterol in terms of its effect on spirometry assessed forced expiratory volume in 1 second (FEV1) over a 24 hour time period.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Indacaterol 300 μg; Drug: Placebo to indacaterol; Drug: Salmeterol 50 μg

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium
    • Novartis Investigator Site
  • Hasselt, Belgium
    • Novartis Investigator Site
  • Herentals, Belgium
    • Novartis Investigator Site
• Spain
  • Alicante, Spain
    • Novartis Investigator Site
  • Alzira, Spain
    • Novartis Investigator Site
  • Madrid, Spain
    • Novartis Investigator Site
  • Mataro, Spain
    • Novartis Investigator Site
• United States
  • Illinois
    • Normal, Illinois, United States
      • Novartis Investigator Site
  • Kansas
    • Shawnee Mission, Kansas, United States
      • Novartis Investigator Site
  • Louisiana
    • Lafayette, Louisiana, United States
      • Novartis Investigator Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • Novartis Investigator Site
    • Raleigh, North Carolina, United States
      • Novartis Investigator Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Novartis Investigator Site
  • South Carolina
    • Spartanburg, South Carolina, United States
      • 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, 2006) and:

  1. Smoking history of at least 20 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 been hospitalized for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period
• Patients requiring long-term oxygen therapy (> 15 hours a day) for chronic hypoxemia
• 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
• Any patient with active cancer or a history of cancer with less than 5 years disease-free survival time
• Patients with a history of long QT syndrome or whose QTc interval (Bazett's) measured at screening or randomization is prolonged
• Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period
• Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements

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: Crossover Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indacaterol 300 μg - placebo to indacaterol - salmeterol 50 μg; In treatment period 1, patients received indacaterol 300 μg once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received placebo to indacaterol once daily for 14 days via SDDPI; and in treatment period 3, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI). There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg; Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to indacaterol; Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Salmeterol 50 μg; Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).
Experimental: Placebo to indacaterol - salmeterol 50 μg - indacaterol 300 μg; In treatment period 1, patients received placebo to indacaterol once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); and in treatment period 3, patients received indacaterol 300 μg once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg; Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to indacaterol; Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Salmeterol 50 μg; Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).
Experimental: Salmeterol 50 μg - indacaterol 300 μg - placebo to indacaterol; In treatment period 1, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); in treatment period 2, patients received indacaterol 300 μg once daily for 14 days via single-dose dry-powder inhaler (SDDPI); and in treatment period 3, patients received placebo to indacaterol once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg; Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to indacaterol; Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Salmeterol 50 μg; Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).
Experimental: Placebo to indacaterol - indacaterol 300 μg - salmeterol 50 μg; In treatment period 1, patients received placebo to indacaterol once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received indacaterol 300 μg once daily for 14 days via SDDPI; and in treatment period 3, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI). There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg; Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to indacaterol; Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Salmeterol 50 μg; Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).
Experimental: Indacaterol 300 μg - salmeterol 50 μg - placebo to indacaterol; In treatment period 1, patients received indacaterol 300 μg once daily for 14 days via single-dose dry-powder inhaler (SDDPI); in treatment period 2, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); and in treatment period 3, patients received placebo to indacaterol once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg; Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to indacaterol; Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Salmeterol 50 μg; Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).
Experimental: Salmeterol 50 μg - placebo to indacaterol - indacaterol 300 μg; In treatment period 1, patients received salmeterol 50 μg twice daily for 14 days via multi-dose dry-powder inhaler (MDDPI); in treatment period 2, patients received placebo to indacaterol once daily for 14 days via single-dose dry-powder inhaler (SDDPI); and in treatment period 3, patients received indacaterol 300 μg once daily for 14 days via SDDPI. There was a washout period of 14 days between each treatment period. Indacaterol and placebo to indacaterol were administered double-blind; salmeterol was administered open-label. 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 300 μg; Indacaterol 300 μg was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Placebo to indacaterol; Placebo to indacaterol was provided in powder filled capsules with a single-dose dry-powder inhaler (SDDPI).; Drug: Salmeterol 50 μg; Salmeterol 50 μg was provided in powder filled capsules with a multi-dose dry-powder inhaler (MDDPI).

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 Each Treatment Period (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 each treatment period. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	After 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in 1 Second (FEV1) 5 Minutes Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	5 minutes post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 15 Minutes Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	15 minutes post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 30 Minutes Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	30 minutes post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 1 Hour Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	1 hour post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 2 Hours Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	2 hours post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 3 Hours Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	3 hours post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 4 Hours Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	4 hours post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 5 Hours Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	5 hours post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 6 Hours Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	6 hours post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 8 Hours Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	8 hours post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 10 Hours Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	10 hours post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 11 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	11 hours 10 minutes post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 11 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	11 hours 45 minutes post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 14 Hours Post-dose at the End of Each Treatment Period (Day 14)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	14 hours post-dose at the end of each treatment period (Day 14)
Forced Expiratory Volume in 1 Second (FEV1) 20 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	20 hours 10 minutes post-dose at the end of each treatment period (Day 15)
Forced Expiratory Volume in 1 Second (FEV1) 20 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	20 hours 45 minutes post-dose at the end of each treatment period (Day 15)
Forced Expiratory Volume in 1 Second (FEV1) 22 Hours Post-dose at the End of Each Treatment Period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	22 hours post-dose at the end of each treatment period (Day 15)
Forced Expiratory Volume in 1 Second (FEV1) 23 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	23 hours 10 minutes post-dose at the end of each treatment period (Day 15)
Forced Expiratory Volume in 1 Second (FEV1) 23 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 15)	FEV1 was measured with spirometry conducted according to internationally accepted standards. The analysis included baseline FEV1, defined as the average of the FEV1 values measured at 50 and 15 minutes prior to the first study drug administration in that period, as a covariate.	23 hours 45 minutes post-dose at the end of each treatment period (Day 15)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: February 4, 2008
• First Submitted That Met QC Criteria: February 22, 2008
• First Posted (Estimate): February 25, 2008

Study Record Updates

• Last Update Posted (Estimate): August 18, 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; indacaterol; chronic obstructive pulmonary disease
• 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: CQAB149B2340