Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This study is designed to collect long term safety data of indacaterol (300 µg o.d.) in Japanese patients with moderate to severe COPD. Data from this study will be used for the registration of indacaterol in Japan.

Official Title
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A 52-week Treatment, Multi-center, Randomized, Open Label, Parallel Group Study to Assess the Long Term Safety and Efficacy of Indacaterol (300 µg o.d.) Using Salmeterol (50 µg b.i.d.) as an Active Control in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Indacaterol 300 µg
* Drug: Salmeterol 50 µg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines) and: Smoking history of at least 20 pack-years Post-bronchodilator FEV1 <80% and ≥30% of the predicted normal value Post-bronchodilator FEV1/FVC (forced vital capacity) <70% Exclusion Criteria: Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1 Patients with concomitant pulmonary disease Patients with a history of asthma Patients with diabetes Type I or uncontrolled diabetes Type II Any patient with lung cancer or a history of lung cancer Patients with a history of certain cardiovascular comorbid conditions Patients who have been exposed to indacaterol previously. (Except for any patient who enrolled in Study CQAB149B1302) 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol 300 µg<br>Indacaterol 300 μg once a day (o.d.) delivered via single dose dry powder inhaler (SDDPI). Daily ICS monotherapy, if needed, was allowed to remain stable throughout study. Salbutamol was available for rescue use throughout study. | Drug: Indacaterol 300 µg<br>* Indacaterol 300 µg once daily (od) via SDDPI<br>|
| Active Comparator: Salmeterol 50 µg<br>Salmeterol 50 μg twice a day (b.i.d.) delivered via Diskus®. Daily ICS monotherapy, if needed, was allowed to remain stable throughout study. Salbutamol was available for rescue use throughout study. | Drug: Salmeterol 50 µg<br>* Salmeterol 50 µg twice daily (bid) via Diskus®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment | The number of participants with newly occurring or worsening clinically notable vital sign: Pulse Rate in beats per minute (bpm) at anytime post baseline (BL) by treatment. Low Pulse Rate was defined as a pulse rate <40 bpm or <= to 50 bpm and a decrease from baseline >= to 15 bpm. High Pulse Rate was defined as a pulse rate >130 bpm or >= to 120 bpm and an increase from baseline >= to 15 bpm. | 52 weeks | 
| The Number of Participants With a Clinically Notable Systolic Blood Pressure During 52 Weeks of Treatment | The number of participants with newly occurring or worsening clinically notable vital sign: Systolic Blood Pressure (mmHg) at anytime post baseline (BL) by treatment. A Low Systolic Blood Pressure was defined as a systolic blood pressure measurement: <75 mmHg or <= to 90 mmHg and a decrease from baseline >= to 20 mmHg. A High Systolic Blood Pressure was defined as a systolic blood pressure measurement: >200 mmHg or >= to 180 mmHg and an increase from baseline >= to 20 mmHg. | 52 weeks | 
| The Number of Participants With a Clinically Notable Diastolic Blood Pressure During 52 Weeks of Treatment | The number of participants with newly occurring or worsening clinically notable vital sign: Diastolic blood pressure (mmHg) at anytime post baseline (BL) by treatment. A Low Diastolic Blood Pressure was defined as a diastolic blood pressure measurement: <40 mmHg or <= to 50 mmHg and a decrease from baseline >= to 15 mmHg. A High Diastolic Blood Pressure was defined as a diastolic blood pressure measurement: >115 mmHg or >= to 105 mmHg and an increase from baseline >= to 15 mmHg. | 52 weeks | 
| The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment | The number of participants with newly occurring or worsening clinically notable QTc Interval value at anytime post baseline. The QTc interval is calculated using Fridericia's formula: QTc= QT/cube root RR. QTc is the interval between the Q and T waves corrected for heart rate and RR is the interval between two R waves in milliseconds (ms). Notable QTc interval >450 ms for males and >470 ms for females. The maximum QTc increase from baseline at any time during the study was also tabulated with absolute and relative frequencies for categories 30- 60 ms and >60 ms. | 52 weeks | 
| Serum Potassium (mmol/L) at Weeks 4, 8, 12, 24, 36, 44, and 52 | The least squares mean of the serum potassium in mmol/L at weeks 4, 8, 12, 24, 36, 44 and 52. Mixed model used baseline serum potassium as a covariate. | 4, 8, 12, 24, 36, 44, and 52 weeks | 
| Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 4, 8, 12, 24, 36, 44, and 52 | The least squares mean of the blood glucose in mmol/L at weeks 4, 8, 12, 24, 36, 44 and 52. Mixed model used baseline blood glucose as a covariate. | 4, 8, 12, 24, 36, 44, and 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) After 12, 24 and 52 Weeks | Trough FEV1 was defined as the mean of the values at 23 h 10 min and 23 h 45 min after dosing at clinic on the previous day. Trough FEV1 was analyzed after 12, 24 and 52 weeks using a mixed model which contained the baseline FEV1 measurement, FEV1 prior to inhalation and FEV1 30 minutes post inhalation of salbutamol as covariates. | After 12, 24 and 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Chronic Obstructive Pulmonary Disease, Indacaterol, long acting β2-agonist