Safety, Tolerability and Efficacy 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 evaluated the 1 year safety, tolerability and efficacy of indacaterol against placebo in the treatment of Chronic Obstructive Pulmonary Disease (COPD) patients

Official Title
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A 26-week Extension to a 26-week Treatment, Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptive, Seamless, Parallel-group Study to Assess Safety, Tolerability and Efficacy of Two Doses of Indacaterol (150 and 300 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease

Conditions
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COPD

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients eligible to participate in the study extension, by definition, will have met the inclusion and exclusion criteria for the core 26 weeks and not met the withdrawal criteria for the core study B2335S at Visit 14 (the last visit of the core study B2335S and the first visit of the extension study B2335SE). In addition the following inclusion/exclusion criteria specified below must be met. Patients must complete Stage 2 of the core study B2335S (NCT00463567). Written informed consent to participate in the extension must be obtained. Patients must be able to comply with all study requirements. Exclusion Criteria: Patients who were randomized to open-label tiotropium in Study B2335S. Patients who participated in Stage 1 of the core study (B2335S). Patients discontinued irrespective of the reason from Stage 2 of the core study. Patients who fail to comply with the core protocol requirements and procedures. Concomitant medical conditions that may interfere with interpretation of study results as defined in the core study protocol. Patients who in the Investigator's opinion should not participate in the extension study. 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol 150 µg<br>Indacaterol 150 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | Drug: Indacaterol<br>* Indacaterol once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI)<br>|
| Experimental: Indacaterol 300 µg<br>Indacaterol 300 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | Drug: Indacaterol<br>* Indacaterol once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI)<br>|
| Placebo Comparator: Placebo<br>Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | Drug: Placebo<br>* Placebo once-daily (o.d.) via 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 |
| --- | --- | --- |
| The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo | 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. | Up to 52 weeks | 
| The Number of Participants With a Clinically Notable Systolic Blood Pressure During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo | 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. | Up to 52 weeks | 
| The Number of Participants With a Clinically Notable Diastolic Blood Pressure During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo | 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. | Up to 52 weeks | 
| The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo | 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 pre to post dose at any time during the study was also tabulated with absolute and relative frequencies for categories 30- 60 ms and >60 ms. | Up to 52 weeks | 
| Serum Potassium (mmol/L) 1 Hour Post-dose at Weeks 12, 26, 36, 44 and 52 | The least squares mean of the serum potassium in mmol/L at weeks 12, 26, 36, 44 and 52. Mixed model used baseline serum potassium as a covariate. | Weeks 12, 26, 36, 44 and 52 | 
| Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 12, 26, 36, 44 and 52 | The least squares mean of the blood glucose in mmol/L at weeks 12, 26, 36, 44 and 52. Mixed model used baseline blood glucose as a covariate. | Weeks 12, 26, 36, 44 and 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 52 of Treatment | Spirometry was conducted according to internationally accepted standards. The trough FEV1 was defined as the average of the FEV1 measurements taken at 23 hours 10 minutes and 23 hours 45 minutes post dose at week 52. The mixed model used baseline FEV1 as well as FEV1 reversibility components as covariates. | Week 52 | 
| Quality of Life Assessment With St George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 36, 44 and 52 | The least squares mean of the SGRQ total score at weeks 36, 44 and 52. Mixed model used for analysis used baseline SGRQ total score as well as FEV1 reversibility components as covariates. SGRQ is a health related quality of life questionnaire consisting of 50 items in three domains: symptoms, activity and impacts. The total score is 0 to 100 with a higher score indicating poorer health. A difference from placebo of -4 in the least squares mean SGRQ total score is considered clinically relevant. | Weeks 36, 44 and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, adults, β2-agonist, indacaterol