An Exploratory Study, to Assess the Effect of Repeat-dose Inhaled Indacaterol Maleate (300 μg) on Dynamic and Static Lung Hyperinflation, Subjective Breathlessness and Health Status in Patients With Chronic Obstructive Pulmonary Disease(COPD)

Study Overview
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Brief Summary
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This study evaluated the effect of QAB149 on dynamic and static hyperinflation, breathlessness, and health status in COPD patients

Official Title
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An Exploratory, Double Blind, Randomized, Placebo-controlled, 2-way Cross-over Study to Assess the Effect of Repeat-dose Inhaled Indacaterol Maleate (300 μg) on Dynamic and Static Lung Hyperinflation, Subjective Breathlessness and Health Status in Patients With COPD

Conditions
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Chronic Obstructive Pulmonary Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects, 40 to 80 years of age, with a documented diagnosis of mild, moderate or severe chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and >20-pack year history of smoking, a post-bronchodilator 40% ≤ FEV1 ≤ 80% of predicted normal and post-bronchodilator FEV1/FVC < 70% who have signed an informed consent form (ICF) prior to the initiation of any study-related procedure (Post bronchodilator refers to 30 minutes after the inhalation of 400 µg of salbutamol) Subjects who demonstrate a plethysmographic functional residual capacity >120% predicted normal Exclusion Criteria: No COPD exacerbations within 6 weeks prior to dosing, no concomitant lung disease such as asthma, no requirement for long term oxygen treatment or history of lung reduction surgery. No medical conditions that would interfere with the performance of spirometry or clinical exercise testing. Any other medical condition that in the opinion of the investigator may cause the patient to be unsuitable for completion of the study or place the patient at potential risk from participating in the study e.g. uncontrolled hypertension or unstable ischemic heart disease Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: Indacaterol 300μg followed by Placebo<br>In period I, indacaterol 300μg was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. In period II, matching placebo was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. For each treatment period and for each patient, the doses were to be administered between 7am and 12am. A period of at least 4 days but no more than 21 days separated each treatment period. Rescue medication (short-acting beta-agonist (SABA)) was prescribed by the investigator for the duration of the study. | Drug: Indacaterol 300μg<br>* 300μg indacaterol maleate inhalation powder in hard gelatin capsules administered via Concept1 inhalation device<br>* Other names: Arcapta;Drug: Placebo<br>* Matching placebo devices and hard gelatin capsules<br>|
| Experimental: Sequence 2 : Placebo followed by Indacaterol 300μg<br>In period I, matching placebo was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. In period II, indacaterol 300μg was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. For each treatment period and for each patient, the doses were to be administered between 7am and 12am. A period of at least 4 days but no more than 21 days separated each treatment period. Rescue medication (short-acting beta-agonist (SABA)) was prescribed by the investigator for the duration of the study. | Drug: Indacaterol 300μg<br>* 300μg indacaterol maleate inhalation powder in hard gelatin capsules administered via Concept1 inhalation device<br>* Other names: Arcapta;Drug: Placebo<br>* Matching placebo devices and hard gelatin capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inspiratory Capacity (IC) at Peak Time and at Isotime on Day 14 | Inspiratory capacity (IC) at peak time and at isotime were the primary pharmacodynamic (PD) variables of interest. IC was measured at two minute intervals during exercise. Isotime was defined as the time the subject was still exercising in the shortest of all sub-maximal exercise tests (3-minutes resting pedaling, 3-minutes unloaded pedaling and exercise with loaded pedaling). Peak time was defined as the last measurement taken in the exercise period. The primary analysis consisted of a linear mixed effects model with baseline IC measurement as covariate. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Static Inspiratory Capacity (IC) at Day 14 | Inspiratory Capacity (IC) at resting (static IC) was measured by using whole body plethysmography. The day 14 measurement was analyzed using an analysis of variance including baseline (day -2) as a covariate, | Day 14 | 
| Trough Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry on Day 14 | 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. The linear mixed model included the baseline FEV1 measurement as covariate. | Day 14 | 
| Chronic Activity Related Breathlessness Measured by Transition Dyspnoea Index (TDI) at Day 14 | Dyspnoea was measured during the treatment period using the transition dyspnoea index (TDI), which captures changes from baseline. The TDI has three domains; functional impairment, magnitude of task and magnitude of effort. TDI domains are rated from -3 (major deterioration) to 3 (major improvement) and rates are summed for transition focal score ranging from -9 to 9; minus scores indicate deterioration. A TDI focal score of 1 was considered to be a clinically significant and meaningful improvement from baseline. Analysis of variance included period baseline dyspnoea index (BDI) as covariate. | Day 14 | 
| Dyspnoea Measured by Borg CR10 Scale at Day 1, Day 14 | The modified Borg CR10 Scale consists of 12-point score that the patients point to so as to indicate their level of dyspnoea (where 0 indicates no breathlessness at all to 12 indicates maximum breathlessness), before and during exercise testing. A reduction in this score indicates an improvement. Isotime was defined as the time the subject was still exercising in the shortest of all sub-maximal exercise tests. Peak time was defined as the last measurement taken in the exercise period. Analysis of variance included period, treatment and sequence as fixed effects and subject as random effect. | Day 1, Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Indacaterol Maleate, Exercise testing