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

Novartis

Status and phase: Completed; Phase 3

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00615030

CQAB149B2305

Details and patient eligibility

About

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

Enrollment: 96 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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96 participants in 12 patient groups

Indacaterol Morning,Indacaterol Evening, Salmeterol

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Indacaterol Evening,Indacaterol Morning, Placebo

Experimental group

Description:

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.

Treatment:

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Salmeterol, Placebo, Indacaterol Morning

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Placebo, Salmeterol, Indacaterol Evening

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Indacaterol Morning, Placebo, Indacaterol Evening

Experimental group

Description:

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.

Treatment:

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Indacaterol Evening,Salmeterol, Indacaterol Morning

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Salmeterol, Indacaterol Evening, Placebo

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Placebo, Indacaterol Morning, Salmeterol

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Indacaterol Morning, Salmeterol, Placebo

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Indacaterol Evening, Placebo, Salmeterol

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Salmeterol, Indacaterol Morning, Indacaterol Evening

Experimental group

Description:

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.

Treatment:

Drug: Salmeterol

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol

Placebo, Indacaterol Evening, Indacaterol Morning

Experimental group

Description:

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.

Treatment:

Drug: Indacaterol

Drug: Placebo to Indacaterol

Drug: Placebo to Salmeterol