Safety of Indacaterol in Patients (≥ 12 Years) With Moder... | NCT00529529

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Indacaterol 300 μg	Experimental	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 07:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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 300 μg Drug: Placebo to indacaterol Drug: Placebo to salmeterol
Indacaterol 600 μg	Experimental	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 07:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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 300 μg Drug: Placebo to salmeterol
Salmeterol 50 μg	Active Comparator	Patients received salmeterol 50 μg delivered via the salmeterol proprietary dry powder inhalation device bis in die (bid, twice daily), once in the morning (between 07:00 and 11:00 AM) and once in the evening (between 7:00 and 11:00 PM). In addition to salmeterol 50 μg, patients received 2 indacaterol placebo inhalations in the morning. 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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Indacaterol 300 μg	Drug	Indacaterol was supplied as powder filled capsules together with a single dose dry powder inhaler (SDDPI).	Indacaterol 300 μg Indacaterol 600 μg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Patients With at Least 1 Adverse Event During the 26 Weeks of the Study	Adverse events include asthma exacerbations. An asthma exacerbation was defined as a worsening of asthma as judged clinically significant by the physician, requiring treatment with rescue oral or intravenous (IV) corticosteroids. Asthma worsening that required treatment with inhaled or nebulized short-acting β2-agonists or an increase in inhaled corticosteroids only was not considered an asthma exacerbation.	Baseline (Day 1) to end of study (Week 26)
Systolic Blood Pressure 1 Hour Post-dose at Day 1	Systolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. The analysis included baseline systolic blood pressure and forced expiratory volume in 1 second (FEV1) pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.	Day 1
Systolic Blood Pressure 1 Hour Post-dose at Week 12	Systolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. The analysis included baseline systolic blood pressure and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.	Week 12
Diastolic Blood Pressure 1 Hour Post-dose at Day 1	Diastolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. Phase V Korotkoff sounds were used for determination of diastolic pressure. The analysis included baseline diastolic blood pressure and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

Secondary Outcomes

Measure	Description	Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at Week 12 + 1 Day, Day 85	FEV1 (in liters, L) was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Week 12, Day 85. The analysis included baseline FEV1 and FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening as covariates.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female patients aged ≥ 12 years (or ≥ 18 years depending upon regulatory and/or Institutional Review Board/Independent Ethics Committee/Research Ethics Board [IRB/IEC/REB] approval) who have signed an informed consent form.
Patients with moderate to severe persistent asthma, diagnosed according to the Global Initiative for Asthma (GINA) guidelines (Updated 2006) and who additionally meet the following criteria:
- Patients who have used treatment with a bronchodilator, either regularly or on-demand, and who had used a daily dose of at least 100 μg beclomethasone dipropionate (or equivalent) for at least 1 month prior to screening.
- Patients whose forced expiratory volume in 1 second (FEV1) is ≥ 50% of the predicted normal value.
- Patients with documented (in the previous 6 months) or who demonstrate (prior to randomization) a ≥ 12% and at least 200 ml increase in FEV1, after inhaling 200 μg salbutamol.

Exclusion Criteria:

Pregnant or nursing (lactating) women and women of child-bearing potential UNLESS they meet pre-specified definitions of post-menopausal or are using pre-specified acceptable methods of contraception.
Patients who have used tobacco products within the 12 month period prior to screening, or who have a smoking history of greater than 10 pack years.
Patients who suffer from chronic obstructive pulmonary disease (COPD) as diagnosed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (2006).
Patients who have had emergency room treatment for an acute asthma attack in the 6 weeks prior to screening or who have been hospitalized for an acute asthma attack in the 6 months prior to screening, or at any time between screening and Week 1.
Patients with diabetes Type I or those with uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range or glycosylated hemoglobin (HbA1C) > 8.0% measured at screening.
Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically significant condition or a clinically relevant laboratory abnormality that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study.
Patients with a history of long QT syndrome, or whose QTc interval (Bazett's formula) is prolonged to > 450 ms (males) or > 470 ms (females).
Certain medications for asthma and allied conditions such as long-acting bronchodilators must not be used prior to screening and for a pre-specified minimum washout period.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigator Site		Glendale	Arizona	85306	United States
Novartis Investigator Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
BG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.
BG002	Salmeterol 50 μg	Patients received salmeterol 50 μg delivered via the salmeterol proprietary dry powder inhalation device bis in die (bid, twice daily), once in the morning (between 7:00 and 11:00 AM) and once in the evening (between 7:00 and 11:00 PM). In addition to salmeterol 50 μg, patients received 2 indacaterol placebo inhalations in the morning. 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.
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Patients With at Least 1 Adverse Event During the 26 Weeks of the Study

Adverse events include asthma exacerbations. An asthma exacerbation was defined as a worsening of asthma as judged clinically significant by the physician, requiring treatment with rescue oral or intravenous (IV) corticosteroids. Asthma worsening that required treatment with inhaled or nebulized short-acting β2-agonists or an increase in inhaled corticosteroids only was not considered an asthma exacerbation.

Safety population: All patients who received at least one dose of study drug.

Posted

Number

Percentage of patients

Baseline (Day 1) to end of study (Week 26)

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.
OG002	Salmeterol 50 μg	Patients received salmeterol 50 μg delivered via the salmeterol proprietary dry powder inhalation device bis in die (bid, twice daily), once in the morning (between 7:00 and 11:00 AM) and once in the evening (between 7:00 and 11:00 PM). In addition to salmeterol 50 μg, patients received 2 indacaterol placebo inhalations in the morning. 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.

Units	Counts
Participants	OG000268 OG001268 OG002269

Title

Denominators

Categories

Title	Measurements
	OG00054.9 OG00166.4 OG00267.3

Primary

Systolic Blood Pressure 1 Hour Post-dose at Day 1

Systolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. The analysis included baseline systolic blood pressure and forced expiratory volume in 1 second (FEV1) pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in the analysis.

Posted

Least Squares Mean

Standard Error

mmHg

Day 1

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

Systolic Blood Pressure 1 Hour Post-dose at Week 12

Systolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. The analysis included baseline systolic blood pressure and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.

Posted

Least Squares Mean

Standard Error

mmHg

Week 12

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

Diastolic Blood Pressure 1 Hour Post-dose at Day 1

Diastolic blood pressure measurements (in millimeters of mercury, mmHg) were made 1 hour post-dose after the patient had rested in the sitting position for at least 10 minutes. Measurements were made using an inflatable cuff around the upper arm. Phase V Korotkoff sounds were used for determination of diastolic pressure. The analysis included baseline diastolic blood pressure and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in this analysis.

Posted

Least Squares Mean

Standard Error

mmHg

Day 1

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

Diastolic Blood Pressure 1 Hour Post-dose at Week 12

Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.

Posted

Least Squares Mean

Standard Error

mmHg

Week 12

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Day 1

The QTc interval (in milliseconds, ms) is calculated from electrocardiogram (ECG) data collected 1 hour post-dose using Fridericia's formula: QTc = QT/RR^0.33. QTc is the interval between the Q and T waves corrected for heart rate and RR is the interval between two R waves. ECGs included all 12 standard leads and a Lead II rhythm strip of at least 10-second duration. All results were sent to a central laboratory for review by a cardiologist. The analysis included baseline QTc interval and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in the analysis.

Posted

Least Squares Mean

Standard Error

Day 1

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg

Primary

Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 12

Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.

Posted

Least Squares Mean

Standard Error

Week 12

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg

Primary

Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 21

Safety population: All patients who received at least one dose of study drug. Participants with observations at week 21 were included in the analysis.

Posted

Least Squares Mean

Standard Error

Week 21

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg

Primary

24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 12

Continuous 24 hour electrocardiography (Holter monitoring) was conducted in a subset of patients at designated study centers, and was used to calculate the mean heart rate (in beats per minute, bpm). Patients returned the Holter monitor recorder to the clinic the morning after the 24 hour recording was complete. The results of Holter monitoring were processed centrally. The analysis included baseline 24 hour mean heart rate and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.

Posted

Least Squares Mean

Standard Error

bpm

Week 12

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 26

Safety population: All patients who received at least one dose of study drug. Participants with observations at week 26 were included in the analysis.

Posted

Least Squares Mean

Standard Error

bpm

Week 26

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

Serum Potassium 1 Hour Post-dose at Day 1

Serum potassium (in millimoles per liter, mmol/L) was measured from venous blood samples. Samples were sent to a central laboratory for analysis. The analysis included baseline serum potassium and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in the analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Day 1

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

Serum Potassium 1 Hour Post-dose at Week 12

Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Week 12

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

Blood Glucose 1 Hour Post-dose at Day 1

Blood glucose (in millimoles per liter, mmol/L) was measured from venous blood samples. Samples were sent to a central laboratory for analysis. The analysis included baseline blood glucose and FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening as covariates.

Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in the analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Day 1

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

Blood Glucose 1 Hour Post-dose at Week 12

Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.

Posted

Least Squares Mean

Standard Error

mmol/L

Week 12

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Primary

Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study

A clinically significant asthma exacerbation was defined as a worsening of asthma as judged clinically significant by the physician, requiring treatment with systemic corticosteroids. This includes events recorded on the asthma exacerbation clinical report form (CRF) page and events recorded on the adverse events CRF page with "asthma" as a key word in the preferred term.

Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug.

Posted

Number

Percentage of patients

Baseline (Day 1) to end of study (Week 26)

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Secondary

Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at Week 12 + 1 Day, Day 85

FEV1 (in liters, L) was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Week 12, Day 85. The analysis included baseline FEV1 and FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening as covariates.

Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Participants with observations at Day 85 were included in the analysis.

Posted

Least Squares Mean

Standard Error

Liters

24 hours post-dose at Week 12 + 1 day, Day 85

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Secondary

Number of Asthma Exacerbations Per Patient (Without Imputation) During the 26 Weeks of the Study

An asthma exacerbation was defined as a worsening of asthma as judged clinically significant by the physician, requiring treatment with rescue oral or intravenous (IV) corticosteroids. The number of asthma exacerbations includes events recorded on the asthma exacerbation clinical report form (CRF) page and events recorded on the adverse events CRF page with "asthma" as a key word in the preferred term.

Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug.

Posted

Mean

Standard Deviation

Asthma exacerbations

Baseline (Day 1) to end of study (Week 26)

ID	Title	Description
OG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.
OG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Indacaterol 300 μg	Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 300 μg, patients received indacaterol and salmeterol placebo inhalations in the morning and salmeterol placebo inhalation in the evening (between 7:00 and 11:00 PM). 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.	5	268	86	268
EG001	Indacaterol 600 μg	Patients received indacaterol 600 μg (2 x 300 μg capsules) delivered via single dose dry powder inhalers (SDDPI) once daily (od) in the morning (between 7:00 and 11:00 AM). In addition to indacaterol 600 μg, patients received salmeterol placebo inhalation in the morning and the evening (between 7:00 and 11:00 PM). 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.	11	268	105	268
EG002	Salmeterol 50 μg	Patients received salmeterol 50 μg delivered via the salmeterol proprietary dry powder inhalation device bis in die (bid, twice daily), once in the morning (between 7:00 and 11:00 AM) and once in the evening (between 7:00 and 11:00 PM). In addition to salmeterol 50 μg, patients received 2 indacaterol placebo inhalations in the morning. 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.	8	269	101	269

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Splenic cyst	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0011 affected268 at risk EG0020 affected269 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0011 affected268 at risk EG0020 affected269 at risk
Cardiac arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected268 at risk EG0010 affected268 at risk EG0020 affected269 at risk
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0010 affected268 at risk EG0021 affected269 at risk
Sudden death	General disorders	MedDRA	Systematic Assessment	EG0001 affected268 at risk EG0010 affected268 at risk EG0020 affected269 at risk
Biliary colic	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0010 affected268 at risk EG0021 affected269 at risk
Cholangitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0011 affected268 at risk EG0020 affected269 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0010 affected268 at risk EG0021 affected269 at risk
Drug hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0010 affected268 at risk EG0021 affected269 at risk
Food allergy	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0011 affected268 at risk EG0020 affected269 at risk
Abscess neck	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected268 at risk EG0010 affected268 at risk EG0020 affected269 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0011 affected268 at risk EG0021 affected269 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected268 at risk EG0010 affected268 at risk EG0020 affected269 at risk
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0012 affected268 at risk EG0020 affected269 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0010 affected268 at risk EG0021 affected269 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0011 affected268 at risk EG0020 affected269 at risk
Multiple fractures	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0011 affected268 at risk EG0020 affected269 at risk
Facial paresis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0010 affected268 at risk EG0021 affected269 at risk
Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0012 affected268 at risk EG0021 affected269 at risk
Stress	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected268 at risk EG0010 affected268 at risk EG0020 affected269 at risk
Analgesic asthma syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0010 affected268 at risk EG0021 affected269 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected268 at risk EG0013 affected268 at risk EG0020 affected269 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0010 affected268 at risk EG0021 affected269 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected268 at risk EG0010 affected268 at risk EG0021 affected269 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG00010 affected268 at risk EG00113 affected268 at risk EG00216 affected269 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00020 affected268 at risk EG00122 affected268 at risk EG00226 affected269 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00017 affected268 at risk EG00127 affected268 at risk EG00218 affected269 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00014 affected268 at risk EG00118 affected268 at risk EG00220 affected269 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00030 affected268 at risk EG00139 affected268 at risk EG00240 affected269 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00028 affected268 at risk EG00129 affected268 at risk EG00214 affected269 at risk

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Term
D000420	Albuterol
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D000588	Amines
D010627	Phenethylamines
D005021	Ethylamines