Study of Indacaterol Dosed in the Evening in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00615030
First received: February 1, 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 the spirometry assessment forced expiratory volume in 1 second [FEV1]) over the full 24-h time period


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: Indacaterol
Drug: Salmeterol
Drug: Placebo to Indacaterol
Drug: Placebo to Salmeterol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Double Blind, Double Dummy, Placebo Controlled, Multicenter, 4 Treatments, 3 Period Incomplete Block Crossover Study to Assess the Efficacy and Safety of Indacaterol 300 µg o.d. Dosed in the Evening in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Salmeterol 50 µg b.i.d. 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) Following 14 Days of Evening Dosing of Indacaterol Versus Placebo [ Time Frame: After 14 days of treatment ] [ Designated as safety issue: No ]

    Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 10 min and 23h 45 min post dose. The primary variable was analyzed using an analysis of covariance (ANCOVA) model with the (period) baseline FEV1 as covariate.

    The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.



Secondary Outcome Measures:
  • Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons [ Time Frame: After 14 days of dosing ] [ Designated as safety issue: No ]
    Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. On the morning and evening of Day 15 trough FEV1 (i.e. mean of measurements performed 23 h 10 min and 23 h 45 min post-dose) were assessed. An analysis of covariance (ANCOVA) model was used with the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.


Enrollment: 96
Study Start Date: January 2008
Study Completion Date: August 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Indacaterol Morning,Indacaterol Evening, Salmeterol
In period I, indacaterol 300 μg once a day in the morning delivered via single dose dry powder inhaler (SDDPI) with a placebo to salmeterol delivered via dry powder inhaler (DPI). Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period II, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period III, Salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and second dose in the evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Salmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
Other Name: Serevent®
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Evening,Indacaterol Morning, Placebo
In period I, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period II, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period III, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Salmeterol, Placebo, Indacaterol Morning
In period I, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose was in the evening along with placebo matching indacaterol delivered by SDDPI. In period II, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period III, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Salmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
Other Name: Serevent®
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Placebo, Salmeterol, Indacaterol Evening
In period I, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period II, salmeterol 50 μg twice daily delivered via dry powder inhaler (DPI). One of the two daily doses of salmeterol was administered in the morning and the second dose was in the evening along with placebo matching indacaterol delivered by SDDPI. In period III, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via dry DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Salmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
Other Name: Serevent®
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Morning, Placebo, Indacaterol Evening
In period I, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period II, During morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period III, Patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Evening,Salmeterol, Indacaterol Morning
In period I, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period II, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period III, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Salmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
Other Name: Serevent®
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Salmeterol, Indacaterol Evening, Placebo
In period I, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period II, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period III, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Salmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
Other Name: Serevent®
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Placebo, Indacaterol Morning, Salmeterol
In period I, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period II, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via dry powder inhaler DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period III, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Salmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
Other Name: Serevent®
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Morning, Salmeterol, Placebo
In period I, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period II, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period III, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Salmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
Other Name: Serevent®
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Indacaterol Evening, Placebo, Salmeterol
In period I, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via dry powder inhaler DPI. In period II, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period III, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Salmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
Other Name: Serevent®
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Salmeterol, Indacaterol Morning, Indacaterol Evening
In period I, salmeterol 50 μg twice daily delivered via DPI. One of the two daily doses of salmeterol was administered in the morning and the second dose in evening along with placebo matching indacaterol delivered by SDDPI. In period II, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. In period III, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Salmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
Other Name: Serevent®
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI
Experimental: Placebo, Indacaterol Evening, Indacaterol Morning
In period, during morning and evening, placebo matching indacaterol was delivered via SDDPI and placebo matching salmeterol was delivered via DPI. In period II, patients were instructed to take morning doses of a placebo to indacaterol delivered via SDDPI and placebo to salmeterol delivered via DPI. Indacaterol 300 μg once a day in the evening delivered via SDDPI with placebo to salmeterol delivered via DPI. In period III, indacaterol 300 μg once a day in the morning delivered via SDDPI with a placebo to salmeterol delivered via DPI. Patients were also instructed to take evening doses of a placebo to indacaterol via SDDPI and placebo to salmeterol via DPI. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
Drug: Indacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
Other Name: QAB149
Drug: Placebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Drug: Placebo to Salmeterol
Placebo matching salmeterol was delivered via DPI

  Eligibility

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

Inclusion criteria:

  • Male and female adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure
  • Co-operative outpatients with a 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:
  • Smoking history of at least 20 pack years
  • Post-bronchodilator FEV1 < 80% and ≥30% of the predicted normal value
  • Post-bronchodilator FEV1/forced vital capacity (FVC) < 70%

Exclusion criteria:

  • Pregnant or lactating females
  • Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period
  • Patients requiring long term oxygen therapy (>15 h a day)
  • Patient who have had a respiratory tract infection 6 weeks prior to V2 (with further criteria)
  • Patients with concomitant pulmonary disease, pulmonary tuberculosis, or clinically significant bronchiectasis
  • Patients with history of asthma (with further criteria)
  • Patients with Type I or uncontrolled type II diabetes.
  • Patients who have clinically relevant laboratory abnormalities or a clinically significant abnormality
  • Any patient with active cancer or a history of cancer with less than 5 years disease free survival time
  • Patient with a history with long QT syndrome or whose QTc interval is prolonged
  • Patients with a hypersensitivity to any of the study drugs or drugs with similar chemical structure
  • Patients who have had treatment with an investigational drug (with further criteria)
  • Patients who have had live attenuated vaccination within 30 days prior to Visit 2, or during run-in period
  • Patients with known history of non compliance to medication
  • Patients unable to satisfactorily use a dry powder inhaler device or perform spirometry measurements

Other protocol-defined inclusion/exclusion criteria may apply

  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: NCT00615030

Locations
France
Novartis Investigative Site
Beuvry, France
Novartis Investigative Site
Nantes, France
Germany
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Hamburg, Germany
Novartis Investigative Site
Leipzig, Germany
Novartis Investigative Site
Mainz, Germany
Spain
Novartis Investigative Site
Barcelona, Spain
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: Novartis Pharmaceuticals + 41 61 324 1111
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00615030     History of Changes
Other Study ID Numbers: CQAB149B2305
Study First Received: February 1, 2008
Results First Received: July 22, 2011
Last Updated: July 22, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
COPD, bronchodilator, long acting beta agonist, LABA

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Salmeterol
Albuterol
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
Tocolytic Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on September 30, 2014