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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00622635
First received: February 4, 2008
Last updated: July 22, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Indacaterol 300 μg
Drug: Placebo to indacaterol
Drug: Salmeterol 50 μg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Each Treatment Period (Day 15) [ Time Frame: After 14 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Forced Expiratory Volume in 1 Second (FEV1) 5 Minutes Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 5 minutes post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 15 Minutes Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 15 minutes post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 30 Minutes Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 30 minutes post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 1 Hour Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 1 hour post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 2 Hours Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 2 hours post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 3 Hours Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 3 hours post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 4 Hours Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 4 hours post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 5 Hours Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 5 hours post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 6 Hours Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 6 hours post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 8 Hours Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 8 hours post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 10 Hours Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 10 hours post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 11 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 11 hours 10 minutes post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 11 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 11 hours 45 minutes post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 14 Hours Post-dose at the End of Each Treatment Period (Day 14) [ Time Frame: 14 hours post-dose at the end of each treatment period (Day 14) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 20 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 15) [ Time Frame: 20 hours 10 minutes post-dose at the end of each treatment period (Day 15) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 20 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 15) [ Time Frame: 20 hours 45 minutes post-dose at the end of each treatment period (Day 15) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 22 Hours Post-dose at the End of Each Treatment Period (Day 15) [ Time Frame: 22 hours post-dose at the end of each treatment period (Day 15) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 23 Hours 10 Minutes Post-dose at the End of Each Treatment Period (Day 15) [ Time Frame: 23 hours 10 minutes post-dose at the end of each treatment period (Day 15) ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) 23 Hours 45 Minutes Post-dose at the End of Each Treatment Period (Day 15) [ Time Frame: 23 hours 45 minutes post-dose at the end of each treatment period (Day 15) ] [ Designated as safety issue: No ]
    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.


Enrollment: 68
Study Start Date: January 2008
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00622635

Locations
United States, Illinois
Novartis Investigator Site
Normal, Illinois, United States
United States, Kansas
Novartis Investigator Site
Shawnee Mission, Kansas, United States
United States, Louisiana
Novartis Investigator Site
Lafayette, Louisiana, United States
United States, North Carolina
Novartis Investigator Site
Charlotte, North Carolina, United States
Novartis Investigator Site
Raleigh, North Carolina, United States
United States, Ohio
Novartis Investigator site
Cincinnati, Ohio, United States
United States, South Carolina
Novartis Investigator Site
Spartanburg, South Carolina, United States
Belgium
Novartis Investigator Site
Genk, Belgium
Novartis Investigator Site
Hasselt, Belgium
Novartis Investigator Site
Herentals, Belgium
Spain
Novartis Investigator Site
Alicante, Spain
Novartis Investigator site
Alzira, Spain
Novartis Investigator Site
Madrid, Spain
Novartis Investigator site
Mataro, Spain
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00622635     History of Changes
Other Study ID Numbers: CQAB149B2340
Study First Received: February 4, 2008
Results First Received: July 22, 2011
Last Updated: July 22, 2011
Health Authority: United States: Food and Drug Administration
Spain: Spanish Agency of Medicines
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Novartis:
chronic obstructive pulmonary disease
COPD
indacaterol

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Salmeterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014