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

NCT00615030 | Completed Phase 3 Results

• 1 other identifier: CQAB149B2305
• Study Type: interventional
• Target: 96
• Locations: 3 countries
• Sites: 7

Brief Summary

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

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD, bronchodilator, long acting beta agonist, LABA

Outcome Measures

Primary Outcomes (1)

• Trough Forced Expiratory Volume in 1 Second (FEV1) Following 14 Days of Evening Dosing of Indacaterol Versus Placebo

  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.

  After 14 days of treatment

Secondary Outcomes (1)

• Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons

  After 14 days of dosing

Study Arms (12)

Indacaterol Morning,Indacaterol Evening, Salmeterol

EXPERIMENTAL

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; Drug: Salmeterol; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Indacaterol Evening,Indacaterol Morning, Placebo

EXPERIMENTAL

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; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Salmeterol, Placebo, Indacaterol Morning

EXPERIMENTAL

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; Drug: Salmeterol; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Placebo, Salmeterol, Indacaterol Evening

EXPERIMENTAL

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; Drug: Salmeterol; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Indacaterol Morning, Placebo, Indacaterol Evening

EXPERIMENTAL

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; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Indacaterol Evening,Salmeterol, Indacaterol Morning

EXPERIMENTAL

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; Drug: Salmeterol; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Salmeterol, Indacaterol Evening, Placebo

EXPERIMENTAL

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; Drug: Salmeterol; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Placebo, Indacaterol Morning, Salmeterol

EXPERIMENTAL

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; Drug: Salmeterol; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Indacaterol Morning, Salmeterol, Placebo

EXPERIMENTAL

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; Drug: Salmeterol; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Indacaterol Evening, Placebo, Salmeterol

EXPERIMENTAL

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; Drug: Salmeterol; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Salmeterol, Indacaterol Morning, Indacaterol Evening

EXPERIMENTAL

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; Drug: Salmeterol; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Placebo, Indacaterol Evening, Indacaterol Morning

EXPERIMENTAL

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; Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol

Interventions

Indacaterol DRUG

300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)

Also known as: QAB149

Indacaterol Evening, Placebo, Salmeterol; Indacaterol Evening,Indacaterol Morning, Placebo; Indacaterol Evening,Salmeterol, Indacaterol Morning; Indacaterol Morning, Placebo, Indacaterol Evening; Indacaterol Morning, Salmeterol, Placebo; Indacaterol Morning,Indacaterol Evening, Salmeterol; Placebo, Indacaterol Evening, Indacaterol Morning; Placebo, Indacaterol Morning, Salmeterol; Placebo, Salmeterol, Indacaterol Evening; Salmeterol, Indacaterol Evening, Placebo; Salmeterol, Indacaterol Morning, Indacaterol Evening; Salmeterol, Placebo, Indacaterol Morning

Salmeterol DRUG

50 µg twice daily delivered via dry powder inhaler (DPI)

Also known as: Serevent®

Indacaterol Evening, Placebo, Salmeterol; Indacaterol Evening,Salmeterol, Indacaterol Morning; Indacaterol Morning, Salmeterol, Placebo; Indacaterol Morning,Indacaterol Evening, Salmeterol; Placebo, Indacaterol Morning, Salmeterol; Placebo, Salmeterol, Indacaterol Evening; Salmeterol, Indacaterol Evening, Placebo; Salmeterol, Indacaterol Morning, Indacaterol Evening; Salmeterol, Placebo, Indacaterol Morning

Placebo to Indacaterol DRUG

Placebo matching indacaterol was delivered via SDDPI.

Indacaterol Evening, Placebo, Salmeterol; Indacaterol Evening,Indacaterol Morning, Placebo; Indacaterol Evening,Salmeterol, Indacaterol Morning; Indacaterol Morning, Placebo, Indacaterol Evening; Indacaterol Morning, Salmeterol, Placebo; Indacaterol Morning,Indacaterol Evening, Salmeterol; Placebo, Indacaterol Evening, Indacaterol Morning; Placebo, Indacaterol Morning, Salmeterol; Placebo, Salmeterol, Indacaterol Evening; Salmeterol, Indacaterol Evening, Placebo; Salmeterol, Indacaterol Morning, Indacaterol Evening; Salmeterol, Placebo, Indacaterol Morning

Placebo to Salmeterol DRUG

Placebo matching salmeterol was delivered via DPI

Indacaterol Evening, Placebo, Salmeterol; Indacaterol Evening,Indacaterol Morning, Placebo; Indacaterol Evening,Salmeterol, Indacaterol Morning; Indacaterol Morning, Placebo, Indacaterol Evening; Indacaterol Morning, Salmeterol, Placebo; Indacaterol Morning,Indacaterol Evening, Salmeterol; Placebo, Indacaterol Evening, Indacaterol Morning; Placebo, Indacaterol Morning, Salmeterol; Placebo, Salmeterol, Indacaterol Evening; Salmeterol, Indacaterol Evening, Placebo; Salmeterol, Indacaterol Morning, Indacaterol Evening; Salmeterol, Placebo, Indacaterol Morning

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (7)

Novartis Investigative Site

Beuvry, France

Location

Novartis Investigative Site

Nantes, France

Location

Novartis Investigative Site

Berlin, Germany

Location

Novartis Investigative Site

Hamburg, Germany

Location

Novartis Investigative Site

Leipzig, Germany

Location

Novartis Investigative Site

Mainz, Germany

Location

Novartis Investigative Site

Barcelona, Spain

Location

Related Publications (1)

• Magnussen H, Verkindre C, Jack D, Jadayel D, Henley M, Woessner R, Higgins M, Kramer B; INPUT study investigators. Indacaterol once-daily is equally effective dosed in the evening or morning in COPD. Respir Med. 2010 Dec;104(12):1869-76. doi: 10.1016/j.rmed.2010.08.010. Epub 2010 Sep 20.

  PMID: 20850959 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

indacaterol; Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  + 41 61 324 1111

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 1, 2008
• First Posted: February 14, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2008
• Study Completion: August 1, 2008
• Last Updated: August 17, 2011
• Results First Posted: August 17, 2011

Record last verified: 2011-07

Locations

ES (1); FR (2); DE (4)