Study to Determine the Onset of Action of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This study will evaluate the onset of action of indacaterol (150 and 300 µg) as compared to placebo, salbutamol 200 µg and salmeterol/fluticasone 50/500 µg

Official Title
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A Phase III, Randomized, Double-blind, Triple-dummy, Placebo Controlled, Multicenter, 5-period, Single-dose Complete Block Crossover Study to Determine the Onset of Action of Indacaterol (150 and 300 μg) in Patients With Moderate to Severe COPD Using Salbutamol (200 μg) and Salmeterol/Fluticasone (50/500 μg) as Active Controls

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Salmeterol/fluticasone (50/500 μg)
* Drug: Salbutamol (200 µg)
* Drug: Placebo to Indacaterol
* Drug: Placebo to Salmeterol/fluticasone
* Drug: Placebo to salbutamol


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 Patients with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (moderate-to-severe 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%, where FVC is forced vital capacity ('Post-' refers to 15-30 minutes after inhalation of 400 μg of salbutamol at Visit 2) Exclusion Criteria: Pregnant / nursing women or women of child-bearing potential Long term oxygen therapy (more than 15 hours per day) on a daily basis for chronic hypoxemia Patients hospitalized for COPD exacerbation in 6 weeks prior to Visit 2 and up to Visit 3 Respiratory tract infection within 6 weeks prior to Visit 2 and up to Visit 3 Concomitant pulmonary disease, pulmonary tuberculosis (unless chest x-ray confirms no longer active) or clinically significant bronchiectasis Any history of asthma, including: blood eosinophil count >400/mm3; onset of asthma symptoms prior to age 40 years History of long QT syndrome or whose QTc (Bazett's) measured at Visit 2 or Visit 3 is prolonged (>450ms for males or >470ms for females) Clinically relevant lab abnormalities / conditions such as (but not limited to) unstable ischemic heart disease, arrhythmia (excluding stable AF), uncontrolled hypertension, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which in the investigator's opinion might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study Uncontrolled Type I / Type II Diabetes or blood glucose outside normal or HbA1c >8.0% of total hemoglobin measured at Visit 2 Any patient with lung cancer or any active cancer or a history of cancer with less than 5 years disease-free survival time History of hypersensitivity to any of the study drugs Irregular day/night, waking/sleeping cycles e.g. shift workers Live attenuated vaccinations within 30 days prior to Visit 2 Investigational drug within 30 days prior to Visit 2 Known history of non-compliance or not able to use devices or perform spirometry 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut<br>Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Indacaterol 150 μg (Ind 150μg), Salmeterol/fluticasone 50/500 μg (Salm/flut), Indacaterol 300 μg (Ind 300μg), Placebo, Salbutamol 200 μg (Salbut). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. 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<br>* Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI)<br>* Other names: Neohaler;Drug: Salmeterol/fluticasone (50/500 μg)<br>* Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Salbutamol (200 µg)<br>* Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Placebo to Indacaterol<br>* Placebo to indacaterol delivered via SDDPI<br>Drug: Placebo to Salmeterol/fluticasone<br>* Placebo to salmeterol/fluticasone delivered via MDDPI<br>Drug: Placebo to salbutamol<br>* Placebo to salbutamol delivered via MDDPI<br>|
| Experimental: Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo<br>Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Indacaterol 300 μg (Ind 300μg), Indacaterol 150 μg (Ind 150μg), Salbutamol 200 μg (Salbut), Salmeterol/fluticasone 50/500 μg (Salm/flut), Placebo. At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. 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<br>* Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI)<br>* Other names: Neohaler;Drug: Salmeterol/fluticasone (50/500 μg)<br>* Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Salbutamol (200 µg)<br>* Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Placebo to Indacaterol<br>* Placebo to indacaterol delivered via SDDPI<br>Drug: Placebo to Salmeterol/fluticasone<br>* Placebo to salmeterol/fluticasone delivered via MDDPI<br>Drug: Placebo to salbutamol<br>* Placebo to salbutamol delivered via MDDPI<br>|
| Experimental: Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg<br>Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Salmeterol/fluticasone 50/500 μg (Salm/flut), Placebo, Indacaterol 150 μg (Ind 150μg), Salbutamol 200 μg (Salbut), Indacaterol 300 μg (Ind 300μg). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. 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<br>* Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI)<br>* Other names: Neohaler;Drug: Salmeterol/fluticasone (50/500 μg)<br>* Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Salbutamol (200 µg)<br>* Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Placebo to Indacaterol<br>* Placebo to indacaterol delivered via SDDPI<br>Drug: Placebo to Salmeterol/fluticasone<br>* Placebo to salmeterol/fluticasone delivered via MDDPI<br>Drug: Placebo to salbutamol<br>* Placebo to salbutamol delivered via MDDPI<br>|
| Experimental: Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut<br>Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Salbutamol 200 μg (Salbut), Indacaterol 300 μg (Ind 300μg), Placebo, Indacaterol 150 μg (Ind 150μg), Salmeterol/fluticasone 50/500 μg (Salm/flut). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. 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<br>* Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI)<br>* Other names: Neohaler;Drug: Salmeterol/fluticasone (50/500 μg)<br>* Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Salbutamol (200 µg)<br>* Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Placebo to Indacaterol<br>* Placebo to indacaterol delivered via SDDPI<br>Drug: Placebo to Salmeterol/fluticasone<br>* Placebo to salmeterol/fluticasone delivered via MDDPI<br>Drug: Placebo to salbutamol<br>* Placebo to salbutamol delivered via MDDPI<br>|
| Experimental: Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg<br>Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Placebo, Salbutamol 200 μg (Salbut), Salmeterol/fluticasone 50/500 μg (Salm/flut), Indacaterol 300 μg (Ind 300μg), Indacaterol 150 μg (Ind 150μg). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. 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<br>* Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI)<br>* Other names: Neohaler;Drug: Salmeterol/fluticasone (50/500 μg)<br>* Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Salbutamol (200 µg)<br>* Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).<br>Drug: Placebo to Indacaterol<br>* Placebo to indacaterol delivered via SDDPI<br>Drug: Placebo to Salmeterol/fluticasone<br>* Placebo to salmeterol/fluticasone delivered via MDDPI<br>Drug: Placebo to salbutamol<br>* Placebo to salbutamol delivered via MDDPI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose | FEV1 was measured at 5 minutes after dosing with spirometry conducted according to internationally accepted standards. The time of dosing was defined as the time corresponding to the use of the first inhaler device. The primary variable was analyzed using a mixed model containing the period baseline FEV1 as covariate. The period baseline FEV1 was the average of the FEV1 value measured in the clinic at 50 and 15 min prior to the study drug administration in that period. | Five Minutes Post Dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic obstructive pulmonary disease, COPD, indacaterol, adults