Efficacy, Safety, and Tolerability of Once Daily Indacaterol in Chronic Obstructive Pulmonary Disease (COPD) Using Formoterol Twice Daily as Active Control

Novartis

Status and phase: Completed; Phase 3

Conditions: Chronic Obstructive Pulmonary Disease

Treatments: Drug: Placebo to indacaterol; Drug: Placebo to formoterol; Drug: Indacaterol; Drug: Formoterol

Study type: Interventional

Funder types: Industry

Identifiers

NCT00393458

CQAB149B2334

Details and patient eligibility

About

This study was designed to assess the efficacy and long-term safety of 300 and 600 µg doses of indacaterol when delivered via a single-dose dry-powder inhaler (SDDPI) in patients with chronic obstructive pulmonary disease (COPD). Patients were randomized to receive either indacaterol 300 µg once daily, indacaterol 600 µg once daily, formoterol 12 µg twice daily, or placebo.

Enrollment: 1,732 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Male and female adults ≥ 40 years, with a diagnosis of chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2005 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 volume capacity) < 70% (Post refers to within 30 minutes after inhalation of 400 μg of salbutamol)

     Exclusion Criteria:

• Patients who were hospitalized for a COPD exacerbation in the 6 weeks prior to screening.

• Patients who 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.

• Patients with a history of certain cardiovascular co-morbid conditions.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,732 participants in 4 patient groups, including a placebo group

Indacaterol 300 μg plus placebo to formoterol

Experimental group

Description:

Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.

Treatment:

Drug: Placebo to formoterol

Drug: Indacaterol

Indacaterol 600 μg plus placebo to formoterol

Experimental group

Description:

Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.

Treatment:

Drug: Placebo to formoterol

Drug: Indacaterol

Formoterol 12 μg plus placebo to indacaterol

Active Comparator group

Description:

Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.

Treatment:

Drug: Formoterol

Drug: Placebo to indacaterol

Placebo to indacaterol plus placebo to formoterol

Placebo Comparator group

Description:

Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. 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.

Treatment:

Drug: Placebo to formoterol

Drug: Placebo to indacaterol