Effect of Indacaterol on Inspiratory Capacity (IC)

Study Overview
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Brief Summary
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This study is being conducted to assess the effect of indacaterol (150 μg o.d.) on inspiratory capacity (IC), using placebo and open label tiotropium (18 μg o.d.) as comparators in patients with moderate chronic obstructive pulmonary disease (COPD). In particular, spirometric timepoints are included to elucidate the peak-IC in a period of approximately 4 hour post inhalation

Official Title
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A Randomized, Double-blind, Placebo Controlled, Multicenter, 3-period Crossover Study to Compare the Effect of Indacaterol (150μg o.d.) on Inspiratory Capacity to Placebo in Patients With Moderate COPD, Using Open Label Tiotropium (18μg o.d.) as Active Control

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Tiotropium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Co-operative outpatients with a diagnosis of COPD (moderate as classified by the GOLD Guidelines, 2008) and including: Smoking history of at least 10 pack years Post-bronchodilator FEV1 <80% and ≥50% of the predicted normal value (Visit 2). Post-bronchodilator FEV1/forced vital capacity (FVC) <70% (Visit 2). Exclusion Criteria: Patients who received any corticosteroid (including inhaled) for 3 months prior to screening Other protocol-defined inclusion/exclusion criteria may apply

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 - placebo - tiotropium<br>In treatment period 1, patients received indacaterol 150µg once daily; in treatment period 2, patients received placebo to indacaterol once daily; in treatment period 3, patients received tiotropium 18µg once daily. Patients received indacaterol and placebo by single-dose dry powder inhaler (SDDPI); tiotropium was delivered via a proprietary inhalation device. There was a washout period of 13 days between each period. Use of fixed-dose combination of an anticholinergic plus a short-acting β2-agonist and use of long-acting β2-agonists were discontinued. Salbutamol rescue use was allowed during the treatment period as needed. | Drug: Indacaterol<br>* Indacaterol 150µg once daily (o.d.) delivered via single-dose dry powder inhaler (SDDPI)<br>Drug: Tiotropium<br>* Tiotropium 18µg o.d. delivered via a proprietary inhalation device.<br>Drug: Placebo<br>* Placebo to indacaterol o.d. delivered via SDDPI<br>|
| Experimental: Placebo - Tiotropium - Indacaterol<br>In treatment period 1, patients received placebo to indacaterol once daily; in treatment period 2, patients received tiotropium 18µg once daily; in treatment period 3, patients received indacaterol 150µg once daily. Patients received indacaterol and placebo by single-dose dry powder inhaler (SDDPI); tiotropium was delivered via a proprietary inhalation device. There was a washout period of 13 days between each period. Use of fixed-dose combination of an anticholinergic plus a short-acting β2-agonist and use of long-acting β2-agonists were discontinued. Salbutamol rescue use was allowed during the treatment period as needed. | Drug: Indacaterol<br>* Indacaterol 150µg once daily (o.d.) delivered via single-dose dry powder inhaler (SDDPI)<br>Drug: Tiotropium<br>* Tiotropium 18µg o.d. delivered via a proprietary inhalation device.<br>Drug: Placebo<br>* Placebo to indacaterol o.d. delivered via SDDPI<br>|
| Experimental: Tiotropium - indacaterol - placebo<br>In treatment period 1, patients received tiotropium 18µg once daily; in treatment period 2, patients received indacaterol 150µg once daily; in treatment period 3, patients received placebo to indacaterol once daily. Patients received indacaterol and placebo by single-dose dry powder inhaler (SDDPI); tiotropium was delivered via a proprietary inhalation device. There was a washout period of 13 days between each period. Use of fixed-dose combination of an anticholinergic plus a short-acting β2-agonist and use of long-acting β2-agonists were discontinued. Salbutamol rescue use was allowed during the treatment period as needed. | Drug: Indacaterol<br>* Indacaterol 150µg once daily (o.d.) delivered via single-dose dry powder inhaler (SDDPI)<br>Drug: Tiotropium<br>* Tiotropium 18µg o.d. delivered via a proprietary inhalation device.<br>Drug: Placebo<br>* Placebo to indacaterol o.d. delivered via SDDPI<br>|
| Experimental: Placebo - indacaterol - tiotropium<br>In treatment period 1, patients received placebo to indacaterol once daily; in treatment period 2, patients received indacaterol 150µg once daily; in treatment period 3, patients received tiotropium 18µg once daily. Patients received indacaterol and placebo by single-dose dry powder inhaler (SDDPI); tiotropium was delivered via a proprietary inhalation device. There was a washout period of 13 days between each period. Use of fixed-dose combination of an anticholinergic plus a short-acting β2-agonist and use of long-acting β2-agonists were discontinued. Salbutamol rescue use was allowed during the treatment period as needed. | Drug: Indacaterol<br>* Indacaterol 150µg once daily (o.d.) delivered via single-dose dry powder inhaler (SDDPI)<br>Drug: Tiotropium<br>* Tiotropium 18µg o.d. delivered via a proprietary inhalation device.<br>Drug: Placebo<br>* Placebo to indacaterol o.d. delivered via SDDPI<br>|
| Experimental: Indacaterol - tiotropium - placebo<br>In treatment period 1, patients received indacaterol 150µg once daily; in treatment period 2, patients received tiotropium 18µg once daily; in treatment period 3, patients received placebo to indacaterol once daily. Patients received indacaterol and placebo by single-dose dry powder inhaler (SDDPI); tiotropium was delivered via a proprietary inhalation device. There was a washout period of 13 days between each period. Use of fixed-dose combination of an anticholinergic plus a short-acting β2-agonist and use of long-acting β2-agonists were discontinued. Salbutamol rescue use was allowed during the treatment period as needed. | Drug: Indacaterol<br>* Indacaterol 150µg once daily (o.d.) delivered via single-dose dry powder inhaler (SDDPI)<br>Drug: Tiotropium<br>* Tiotropium 18µg o.d. delivered via a proprietary inhalation device.<br>Drug: Placebo<br>* Placebo to indacaterol o.d. delivered via SDDPI<br>|
| Experimental: Tiotropium - placebo - indacaterol<br>In treatment period 1, patients received tiotropium 18µg once daily; in treatment period 2, patients received placebo to indacaterol once daily; in treatment period 3, patients received indacaterol 150µg once daily. Patients received indacaterol and placebo by single-dose dry powder inhaler (SDDPI); tiotropium was delivered via a proprietary inhalation device. There was a washout period of 13 days between each period. Use of fixed-dose combination of an anticholinergic plus a short-acting β2-agonist and use of long-acting β2-agonists were discontinued. Salbutamol rescue use was allowed during the treatment period as needed. | Drug: Indacaterol<br>* Indacaterol 150µg once daily (o.d.) delivered via single-dose dry powder inhaler (SDDPI)<br>Drug: Tiotropium<br>* Tiotropium 18µg o.d. delivered via a proprietary inhalation device.<br>Drug: Placebo<br>* Placebo to indacaterol o.d. delivered via SDDPI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Inspiratory Capacity (IC) After 21 Days of Treatment | IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean over the 3 values which were measured each at 30min, 2 hour, 3 hour and 4 hour post dose by body plethysmography. Analysis of variance model was used with the factors: center, period, treatment, and patients within center. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough IC After 20 Days of Treatment | Trough IC was measured with spirometry conducted according to internationally accepted standards. Trough IC was calculated as the mean of the three measurements of pre-dose body plethysmography (days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center. | 20 days | 
| Peak Residual Volume (RV) After 21 Days of Treatment | Peak RV was measured with spirometry conducted according to internationally accepted standards. Peak RV was calculated as the Total Lung Capacity minus the maximum of the three Inspiratory Vital Capacity measurements which were measured each at 30 min, 2 hours, 3 hours and 4 hours post dose (at days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center. | 21 days | 
| Peak Total Lung Capacity (TLC) After 21 Days of Treatment | TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30 min, 2 hours, 3 hours and 4 hours post dose (at days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center. | 21 days | 
| Peak Residual Volume/Peak Total Lung Capacity (RV/TLC) Ratio After 21 Days of Treatment | Peak RV/TLC ratio was measured with spirometry conducted according to internationally accepted standards. Peak RV/TLC was defined as the peak RV/peak TLC. Analysis of variance model was used with the factors: center, period, treatment, and patients within center. | 21 days | 
| Peak Specific Airway Resistance (sRaw) After 21 Days of Treatment | Peak sRaw was measured with spirometry conducted according to internationally accepted standards. Peak sRaw was the mean of the three measurements which were measured each at 30 min, 2 hours, 3 hours and 4 hours post dose (at days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center. | 21 days | 
| FEV1 30 Minutes Post-dose After 21 Days of Treatment | FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was measured 30 minutes post-dose. Analysis of variance model was used with the factors: center, period, treatment, and patients within center. | 21 days | 
| Trough Forced Expiratory Volume in 1 Second (FEV1) After 20 Days of Treatment | FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was measured pre-dose after 20 days of treatment. Analysis of variance model was used with the factors: center, period, treatment, and patients within center. | 20 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, indacaterol, QAB149, inspiratory capacity