26 Week Efficacy, Safety and Tolerability Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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Stage 1 of the study is designed to provide data about the risk-benefit of 4 dose regimens of indacaterol (75, 150, 300 & 600 µg o.d.) in order to select two doses to carry forward into study Stage 2. Study Stage 2 will provide pivotal confirmation of efficacy, safety, and tolerability of the selected indacaterol doses in patients with COPD

Official Title
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A 26-week Treatment, Multicenter, Randomized, Double Blind, Double Dummy, Placebo-controlled, Adaptive, Seamless, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of Two Doses of Indacaterol (Selected From 75, 150, 300 & 600 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease Using Blinded Formoterol (12 µg b.i.d.) and Open Label Tiotropium (18 µg o.d.) as Active Controls

Conditions
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Pulmonary Disease, Chronic Obstructive, COPD, Lung Diseases, Obstructive

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Formoterol (12 µg b.i.d.)
* Drug: Tiotropium (18 µg o.d.)
* Drug: Placebo to Indacaterol
* Drug: Placebo to Formoterol


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 COPD (moderate to severe as classified by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) Guidelines, 2005) and: Smoking history of at least 20 pack years Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value. Post-bronchodilator FEV1/FVC < 70% (Post refers to within 30 min of inhalation of 400 µg of salbutamol) Exclusion Criteria: Pregnant or lactating females Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period Patients requiring long term oxygen therapy (> 15 h a day) Patients who have had a respiratory tract infection 6 weeks prior to V1 (with further criteria) Patients with concomitant pulmonary disease, pulmonary tuberculosis, or clinically significant bronchiectasis Patients with a history of asthma (with further criteria) Patients with Type I or uncontrolled Type II diabetes Patients with contraindications for tiotropium Patients who have clinically relevant laboratory abnormalities or a clinically significant abnormality 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 is prolonged Patients with a hypersensitivity to any of the study drugs or drugs with similar chemical structures Patients who have had treatment with the investigational drug (with further criteria) Patients who have had live attenuated vaccinations within 30 days prior to visit 1, or during run-in period Patients with known history of non compliance to medication Patients unable to satisfactorily use a dry powder inhaler device or perform spirometry measurements 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 150 µg (Continued Into Stage 2)<br>In the morning, Indacaterol 150 µg once daily orally inhaled via a single dose dry powder inhaler (SDDPI) + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1. Daily Inhaled Corticosteroid (ICS) monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study. | Drug: Indacaterol<br>* In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo to Indacaterol<br>* In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo to Formoterol<br>* In the morning and in the evening, placebo to formoterol delivered via Aerolizer.<br>|
| Experimental: Indacaterol 300 µg (Continued Into Stage 2)<br>In the morning, Indacaterol 300 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study. | Drug: Indacaterol<br>* In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo to Indacaterol<br>* In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo to Formoterol<br>* In the morning and in the evening, placebo to formoterol delivered via Aerolizer.<br>|
| Active Comparator: Tiotropium 18 µg (Continued Into Stage 2)<br>Tiotropium 18 µg dry powder capsules delivered (open label) via manufacturer's proprietary SDDPI, (Handihaler®). Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study. | Drug: Tiotropium (18 µg o.d.)<br>* Tiotropium 18 µg once daily (o.d.) dry powder capsules delivered via a SDDPI.<br>|
| Placebo Comparator: Placebo (Continued Into Stage 2)<br>In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study. | Drug: Placebo to Indacaterol<br>* In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo to Formoterol<br>* In the morning and in the evening, placebo to formoterol delivered via Aerolizer.<br>|
| Experimental: Indacaterol 75 µg (Not Continued into Stage 2)<br>In the morning, Indacaterol 75 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study. | Drug: Indacaterol<br>* In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo to Indacaterol<br>* In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo to Formoterol<br>* In the morning and in the evening, placebo to formoterol delivered via Aerolizer.<br>|
| Experimental: Indacaterol 600 µg (Not Continued Into Stage 2)<br>In the morning, 2 capsules of Indacaterol 300 µg once daily orally inhaled via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study. | Drug: Indacaterol<br>* In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo to Formoterol<br>* In the morning and in the evening, placebo to formoterol delivered via Aerolizer.<br>|
| Active Comparator: Formoterol 12 µg (Not Continued Into Stage 2)<br>In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Formoterol 12 µg delivered via Aerolizer. In evening, Formoterol 12 µg delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study. | Drug: Formoterol (12 µg b.i.d.)<br>* Formoterol 12 µg twice daily (b.i.d.) in the morning and in the evening via an aerolizer.<br>Drug: Placebo to Indacaterol<br>* In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) Assessed by Spirometry 24 Hour Post Dose After 12 Weeks of Treatment | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 h 10 min and the 23 h 45 min post dose values. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates. | after 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Days of Poor Control Reported Over the 26 Week Treatment Period | A Chronic Obstructive Pulmonary Disease (COPD) day of poor control was defined as any day in the participant's diary with a score ≥2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). Score for each symptom ranges from 0-3; a higher number indicates a more severe symptom. The model contained baseline percentage of days of poor control as well as FEV1 reversibility components as covariates. | up to 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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indacaterol, long acting beta-2 agonist