A Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via the TWISTHALER® Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This study will evaluate the dose response relationship among four doses of indacaterol as well as placebo delivered via the TWISTHALER® device.

Official Title
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A Randomized, Multi-center, Parallel Group, Double Blind, Placebo and Formoterol Controlled 14 Day Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via TWISTHALER® Device in Patients With COPD

Conditions
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COPD

Intervention / Treatment
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* Drug: indacaterol
* Drug: formoterol
* Drug: placebo to indacaterol
* Drug: placebo to formoterol
* Drug: short acting β2- agonist


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 (which include any adjustment to their current COPD treatment) Cooperative outpatients with a diagnosis of COPD (moderate to severe as classified by the Global Initiative for Obstructive Lung Disease (GOLD) Guidelines, 2006) and: Smoking history of at least 10 pack years Post-bronchodilator Forced Expiratory Volume in one second (FEV1) < 80% and ≥30% of the predicted normal value. Post-bronchodilator FEV1/Forced vital capacity (FVC) < 70% Exclusion Criteria: Pregnant women, nursing mothers, or females of childbearing potential, regardless of whether or not sexually active, if they are not using acceptable methods of contraception. Patients who have been hospitalized for an exacerbation of their airways disease within 6 weeks prior to Visit 1 or between Visit 1 and Visit 2. Patients with a history of asthma. Patients with an acute respiratory tract infection within 4 weeks prior to Visit 1, will be not allowed to enter the study. Other clinically significant conditions which may interfere with the study conduct or patient safety as specified in the protocol. 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: indacaterol 62.5 μg<br>Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication. | Drug: indacaterol<br>* Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).<br>Drug: placebo to formoterol<br>* Placebo AEROLIZER® device<br>Drug: short acting β2- agonist<br>* 100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).<br>|
| Experimental: indacaterol 125 μg<br>Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication. | Drug: indacaterol<br>* Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).<br>Drug: placebo to formoterol<br>* Placebo AEROLIZER® device<br>Drug: short acting β2- agonist<br>* 100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).<br>|
| Experimental: Indacaterol 250 μg<br>Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication. | Drug: indacaterol<br>* Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).<br>Drug: placebo to formoterol<br>* Placebo AEROLIZER® device<br>Drug: short acting β2- agonist<br>* 100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).<br>|
| Experimental: indacaterol 500 μg<br>Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication. | Drug: indacaterol<br>* Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).<br>Drug: placebo to formoterol<br>* Placebo AEROLIZER® device<br>Drug: short acting β2- agonist<br>* 100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).<br>|
| Active Comparator: formoterol<br>Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication. | Drug: formoterol<br>* Formoterol delivered by oral inhalation via AEROLIZER® inhalation device.<br>Drug: placebo to indacaterol<br>* Placebo TWISTHALER® device<br>Drug: short acting β2- agonist<br>* 100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).<br>|
| Placebo Comparator: placebo<br>Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication. | Drug: placebo to indacaterol<br>* Placebo TWISTHALER® device<br>Drug: placebo to formoterol<br>* Placebo AEROLIZER® device<br>Drug: short acting β2- agonist<br>* 100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 14 days of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate. | Baseline (prior to first dose) and Day 15 (24 hours after last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose | FEV1 was measured on Day 14 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate. | Day 14, pre-dose and at 5, 20, 30 minutes and 1, 2, 3, and 4 hours post-dose. | 
| The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) on Day 1 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 1 day of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate. | Day 1 Baseline (prior to first dose) and 24 hours post-dose. | 
| Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose on Day 1 | FEV1 was measured on Day 1 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate. | Day 1; pre-dose and at 5, 20, 30 minutes and 1, 2, 3, and 4 hours post-dose. | 
| Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Time to peak FEV1 is calculated in minutes from the time of inhalation of study drug to the time of the peak FEV1, which is taken as the maximum FEV1 recorded post-dose. | Day 1 and Day 14 measured pre-dose and up to 4 hours post-dose | 
| Change From Baseline in Morning and Evening Peak Expiratory Flow | The Peak Expiratory Flow (PEF) rate is the maximal rate that a person can exhale during a short maximal expiratory effort after fully inhaling. Participants measured their PEF using a peak flow meter prior to taking study medication and recorded measurements in a diary every morning and evening during the study. Change from baseline is the difference between the mean baseline PEF recorded during the screening period until the first day of treatment, and the overall mean PEF from Days 1 to 14. | Baseline (recorded during the screening period) and Days 1-14 (treatment period). | 
| Number of Participants Using Rescue Medication | Participants recorded the use of rescue medications (salbutamol/albuterol) for treatment of asthma symptoms twice a day in a diary during the 14 days of the treatment period. | Over 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QMF, indacaterol, TWISTHALER® device