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

Overview

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.

Full Title of Study: “A 52-week Treatment, Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol (300 and 600 µg Once Daily) in Patients With Chronic Obstructive Pulmonary Disease, Using Formoterol (12 µg Twice Daily) as an Active Control”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: July 2008

Interventions

  • Drug: Indacaterol
    • Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
  • Drug: Formoterol
    • Formoterol was supplied in powder-filled capsules with the manufacturer’s proprietary inhalation device (Aerolizer®).
  • Drug: Placebo to indacaterol
    • Placebo to indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
  • Drug: Placebo to formoterol
    • Placebo to formoterol was supplied in powder-filled capsules with the manufacturer’s proprietary inhalation device (Aerolizer®).

Arms, Groups and Cohorts

  • Experimental: Indacaterol 300 μg plus placebo to formoterol
    • 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.
  • Experimental: Indacaterol 600 μg plus placebo to formoterol
    • 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.
  • Active Comparator: Formoterol 12 μg plus placebo to indacaterol
    • 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.
  • Placebo Comparator: Placebo to indacaterol plus placebo to formoterol
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85
    • Time Frame: Week 12 + 1 day, Day 85
    • 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 treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Secondary Measures

  • Percentage of Days of Poor Control During 52 Weeks of Treatment
    • Time Frame: Baseline to end of study (Week 52)
    • Percentage of days of poor control was defined as the number of days in the patient diary with a score ≥ 2 (scale of 0-3, a higher number means more severe symptoms) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness) over 52 weeks divided by the number of evaluable days (days with ≥ 2 symptoms with scores). The analysis included baseline percentage of days of poor control, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Novartis
  • Provider of Information About this Clinical Study
    • External Affairs, Novartis
  • Overall Official(s)
    • Novartis Investigator Site, Principal Investigator, Novartis

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