The Effect of Indacaterol on Exercise Endurance in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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This study compared the effect of indacaterol (300 μg once daily [od]) on exercise endurance with that of placebo in patients with moderate to severe chronic obstructive pulmonary disease.

Official Title
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A Phase III Randomized, Double-blind, Placebo-controlled, 2-period Crossover, Multicenter Study to Assess the Effect of Indacaterol (300 μg o.d.) on Exercise Endurance in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Indacaterol 300 μg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 moderate to severe chronic obstructive pulmonary disease (COPD), as classified by the GOLD Guidelines (2006), and: Smoking history of at least 20 pack years. Post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% of the predicted normal value. Post-bronchodilator FEV1/forced vital capacity (FVC) < 70%. Exclusion Criteria: Pregnant or nursing (lactating) women. Women of child-bearing potential. Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period. Patients requiring oxygen therapy or who experience oxygen desaturation to < 80% during cycle exercise on room air. Patients with a Wmax value < 20 W (as determined by the incremental cycle endurance test) at screening. Patients who have had a respiratory tract infection within 6 weeks prior to screening. Patients with contra-indications of cardiopulmonary exercise testing. Patients with concomitant pulmonary disease. Patients with a history (up to and including the screening visit) of asthma. Patients with diabetes Type I or uncontrolled diabetes Type II. Any patient with lung cancer or a history of lung cancer. Any patient with active cancer or a history of cancer with less than 5 years disease free survival time. Patients with a history of long QT syndrome or whose QTc interval (Bazett's) measured at the collection of informed consent visit (Visit 1) or randomization is prolonged. Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period. Patients unable to successfully use a dry powder inhaler device, metered dose inhaler (MDI), or perform spirometry measurements. Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol 300 μg followed by placebo<br>Patients first received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning for 3 weeks. After a 3-week washout period, patients received placebo delivered od via a SDDPI in the morning for 3 weeks. 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. | Drug: Indacaterol 300 μg<br>* Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.<br>Drug: Placebo<br>* Placebo was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.<br>|
| Experimental: Placebo followed by indacaterol 300 μg<br>Patients first received placebo delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning for 3 weeks. After a 3-week washout period, patients received indacaterol 300 μg delivered od via a SDDPI in the morning for 3 weeks. 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. | Drug: Indacaterol 300 μg<br>* Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.<br>Drug: Placebo<br>* Placebo was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Duration Time Assessed by Constant-load Cycle Ergometry at the End of Each Treatment Period | At the end of each 3 week treatment period, patients completed constant-load cycle ergometry testing at a work-rate of 75% of the Wmax determined at Screening. This work-rate was maintained until symptom limitation caused the patient to stop exercising. The time from the start of loaded pedaling until the patient stopped exercising was recorded. | End of each 3 week treatment period (last day of Weeks 3 and 9) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inspiratory Capacity (IC) Assessed at Rest With Spirometry at the End of Each Treatment Period 60 Minutes Pre-dose | At the end of each 3 week treatment period 60 minutes before inhalation of study drug, IC was measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements was calculated and reported in liters. | End of each 3 week treatment period (last day of Weeks 3 and 9) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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indacaterol, chronic obstructive pulmonary disease, exercise endurance, moderate to severe chronic obstructive pulmonary disease, COPD