Asthma
Conditions
Keywords
asthma, QAB149, indacaterol
Brief summary
This study was designed to assess the safety of indacaterol (300 µg and 600 µg (2 x 300 μg capsules) once daily \[od\]), compared with salmeterol (50 μg twice a day \[b.i.d.\]), over 26 weeks, in patients with moderate to severe persistent asthma.
Interventions
Indacaterol was supplied as powder filled capsules together with a single dose dry powder inhaler (SDDPI).
DRUGSalmeterol 50 μg
Salmeterol was supplied as powder filled capsules together with the manufacturer's proprietary dry powder inhalation device.
DRUGPlacebo to indacaterol
Placebo to indacaterol was supplied as powder filled capsules together with a single dose dry powder inhaler (SDDPI).
Placebo to salmeterol was supplied as powder filled capsules together with the manufacturer's proprietary dry powder inhalation device.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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. 2. 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
1. 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. 2. 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. 3. Patients who suffer from chronic obstructive pulmonary disease (COPD) as diagnosed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (2006). 4. 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. 5. 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. 6. 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. 7. 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). 8. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | Baseline (Day 1) to end of study (Week 26) | 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. |
| Blood Glucose 1 Hour Post-dose at Day 1 | 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. |
| Blood Glucose 1 Hour Post-dose at Week 12 | Week 12 | 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. |
| Diastolic Blood Pressure 1 Hour Post-dose at Day 1 | 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. |
| Percentage of Patients With at Least 1 Adverse Event During the 26 Weeks of the Study | Baseline (Day 1) to end of study (Week 26) | 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. |
| Systolic Blood Pressure 1 Hour Post-dose at Day 1 | 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. |
| Systolic Blood Pressure 1 Hour Post-dose at Week 12 | 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. |
| Diastolic Blood Pressure 1 Hour Post-dose at Week 12 | Week 12 | 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. |
| Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Day 1 | 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. |
| Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 12 | Week 12 | 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. |
| Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 21 | Week 21 | 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. |
| 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 12 | 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. |
| 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 26 | Week 26 | 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. |
| Serum Potassium 1 Hour Post-dose at Day 1 | 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. |
| Serum Potassium 1 Hour Post-dose at Week 12 | Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Asthma Exacerbations Per Patient (Without Imputation) During the 26 Weeks of the Study | Baseline (Day 1) to end of study (Week 26) | 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. |
| Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at Week 12 + 1 Day, Day 85 | 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. |
Countries
Argentina, Canada, Czechia, France, Germany, Hungary, Italy, Peru, Slovakia, Spain, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 268 |
| 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. | 268 |
| 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. | 269 |
| Total | 805 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal test procedure result(s) | 1 | 0 | 0 |
| Overall Study | Administrative problems | 1 | 0 | 3 |
| Overall Study | Adverse Event | 12 | 17 | 8 |
| Overall Study | Death | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 5 | 3 | 1 |
| Overall Study | Protocol deviation | 8 | 12 | 5 |
| Overall Study | Subject withdrew consent | 12 | 9 | 12 |
| Overall Study | Unsatisfactory therapeutic effect | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Indacaterol 300 μg | Indacaterol 600 μg | Salmeterol 50 μg | Total |
|---|---|---|---|---|
| Age Continuous | 43.5 years STANDARD_DEVIATION 15.84 | 44.5 years STANDARD_DEVIATION 15.19 | 42.5 years STANDARD_DEVIATION 15.24 | 43.5 years STANDARD_DEVIATION 15.43 |
| Sex: Female, Male Female | 151 Participants | 175 Participants | 164 Participants | 490 Participants |
| Sex: Female, Male Male | 117 Participants | 93 Participants | 105 Participants | 315 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 86 / 268 | 105 / 268 | 101 / 269 |
| serious Total, serious adverse events | 5 / 268 | 11 / 268 | 8 / 269 |
Outcome results
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.
Time frame: Week 12
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 12 | 81.0 bpm | Standard Error 1.1 |
| Indacaterol 600 μg | 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 12 | 81.7 bpm | Standard Error 1.11 |
| Salmeterol 50 μg | 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 12 | 80.4 bpm | Standard Error 1.05 |
Primary
24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 26
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.
Time frame: Week 26
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at week 26 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 26 | 79.4 bpm | Standard Error 0.96 |
| Indacaterol 600 μg | 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 26 | 81.0 bpm | Standard Error 0.96 |
| Salmeterol 50 μg | 24 Hour Mean Heart Rate Determined From ECG Holter Monitoring at Week 26 | 79.2 bpm | Standard Error 0.96 |
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.
Time frame: Day 1
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Blood Glucose 1 Hour Post-dose at Day 1 | 5.24 mmol/L | Standard Error 0.061 |
| Indacaterol 600 μg | Blood Glucose 1 Hour Post-dose at Day 1 | 5.45 mmol/L | Standard Error 0.061 |
| Salmeterol 50 μg | Blood Glucose 1 Hour Post-dose at Day 1 | 5.21 mmol/L | Standard Error 0.062 |
Primary
Blood Glucose 1 Hour Post-dose at Week 12
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.
Time frame: Week 12
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Blood Glucose 1 Hour Post-dose at Week 12 | 5.27 mmol/L | Standard Error 0.068 |
| Indacaterol 600 μg | Blood Glucose 1 Hour Post-dose at Week 12 | 5.38 mmol/L | Standard Error 0.069 |
| Salmeterol 50 μg | Blood Glucose 1 Hour Post-dose at Week 12 | 5.23 mmol/L | Standard Error 0.068 |
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.
Time frame: Day 1
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Day 1 | 404.46 ms | Standard Error 0.706 |
| Indacaterol 600 μg | Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Day 1 | 404.97 ms | Standard Error 0.704 |
| Salmeterol 50 μg | Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Day 1 | 405.05 ms | Standard Error 0.706 |
Primary
Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 12
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.
Time frame: Week 12
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 12 | 404.93 ms | Standard Error 0.97 |
| Indacaterol 600 μg | Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 12 | 407.78 ms | Standard Error 0.979 |
| Salmeterol 50 μg | Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 12 | 406.98 ms | Standard Error 0.967 |
Primary
Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 21
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.
Time frame: Week 21
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at week 21 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 21 | 406.41 ms | Standard Error 1.005 |
| Indacaterol 600 μg | Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 21 | 407.49 ms | Standard Error 1.014 |
| Salmeterol 50 μg | Corrected QT (QTc) Interval Using Fridericia's Formula Measured 1 Hour Post-dose at Week 21 | 407.23 ms | Standard Error 0.995 |
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.
Time frame: Day 1
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Diastolic Blood Pressure 1 Hour Post-dose at Day 1 | 76.67 mmHg | Standard Error 0.484 |
| Indacaterol 600 μg | Diastolic Blood Pressure 1 Hour Post-dose at Day 1 | 76.55 mmHg | Standard Error 0.484 |
| Salmeterol 50 μg | Diastolic Blood Pressure 1 Hour Post-dose at Day 1 | 77.08 mmHg | Standard Error 0.485 |
Primary
Diastolic Blood Pressure 1 Hour Post-dose at Week 12
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.
Time frame: Week 12
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Diastolic Blood Pressure 1 Hour Post-dose at Week 12 | 75.38 mmHg | Standard Error 0.576 |
| Indacaterol 600 μg | Diastolic Blood Pressure 1 Hour Post-dose at Week 12 | 76.11 mmHg | Standard Error 0.58 |
| Salmeterol 50 μg | Diastolic Blood Pressure 1 Hour Post-dose at Week 12 | 76.96 mmHg | Standard Error 0.575 |
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.
Time frame: Baseline (Day 1) to end of study (Week 26)
Population: Safety population: All patients who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Indacaterol 300 μg | Percentage of Patients With at Least 1 Adverse Event During the 26 Weeks of the Study | 54.9 Percentage of patients |
| Indacaterol 600 μg | Percentage of Patients With at Least 1 Adverse Event During the 26 Weeks of the Study | 66.4 Percentage of patients |
| Salmeterol 50 μg | Percentage of Patients With at Least 1 Adverse Event During the 26 Weeks of the Study | 67.3 Percentage of patients |
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.
Time frame: Baseline (Day 1) to end of study (Week 26)
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Indacaterol 300 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 0 exacerbations | 92.9 Percentage of patients |
| Indacaterol 300 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 1 exacerbation | 5.6 Percentage of patients |
| Indacaterol 300 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 2 exacerbations | 0.7 Percentage of patients |
| Indacaterol 300 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 3 exacerbations | 0.7 Percentage of patients |
| Indacaterol 600 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 3 exacerbations | 0.0 Percentage of patients |
| Indacaterol 600 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 0 exacerbations | 89.9 Percentage of patients |
| Indacaterol 600 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 2 exacerbations | 0.7 Percentage of patients |
| Indacaterol 600 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 1 exacerbation | 9.3 Percentage of patients |
| Salmeterol 50 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 3 exacerbations | 0.0 Percentage of patients |
| Salmeterol 50 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 1 exacerbation | 8.6 Percentage of patients |
| Salmeterol 50 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 2 exacerbations | 1.5 Percentage of patients |
| Salmeterol 50 μg | Percentage of Patients With Clinically Significant Asthma Exacerbations During the 26 Weeks of the Study | 0 exacerbations | 90.0 Percentage of patients |
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.
Time frame: Day 1
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Serum Potassium 1 Hour Post-dose at Day 1 | 4.30 mmol/L | Standard Error 0.022 |
| Indacaterol 600 μg | Serum Potassium 1 Hour Post-dose at Day 1 | 4.24 mmol/L | Standard Error 0.023 |
| Salmeterol 50 μg | Serum Potassium 1 Hour Post-dose at Day 1 | 4.32 mmol/L | Standard Error 0.023 |
Primary
Serum Potassium 1 Hour Post-dose at Week 12
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.
Time frame: Week 12
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Serum Potassium 1 Hour Post-dose at Week 12 | 4.31 mmol/L | Standard Error 0.025 |
| Indacaterol 600 μg | Serum Potassium 1 Hour Post-dose at Week 12 | 4.29 mmol/L | Standard Error 0.025 |
| Salmeterol 50 μg | Serum Potassium 1 Hour Post-dose at Week 12 | 4.33 mmol/L | Standard Error 0.025 |
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.
Time frame: Day 1
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at Day 1 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Systolic Blood Pressure 1 Hour Post-dose at Day 1 | 122.79 mmHg | Standard Error 0.605 |
| Indacaterol 600 μg | Systolic Blood Pressure 1 Hour Post-dose at Day 1 | 122.60 mmHg | Standard Error 0.605 |
| Salmeterol 50 μg | Systolic Blood Pressure 1 Hour Post-dose at Day 1 | 122.56 mmHg | Standard Error 0.606 |
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.
Time frame: Week 12
Population: Safety population: All patients who received at least one dose of study drug. Participants with observations at week 12 were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Systolic Blood Pressure 1 Hour Post-dose at Week 12 | 120.29 mmHg | Standard Error 0.802 |
| Indacaterol 600 μg | Systolic Blood Pressure 1 Hour Post-dose at Week 12 | 121.98 mmHg | Standard Error 0.809 |
| Salmeterol 50 μg | Systolic Blood Pressure 1 Hour Post-dose at Week 12 | 122.02 mmHg | Standard Error 0.801 |
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.
Time frame: Baseline (Day 1) to end of study (Week 26)
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Number of Asthma Exacerbations Per Patient (Without Imputation) During the 26 Weeks of the Study | 0.17 Asthma exacerbations | Standard Deviation 0.561 |
| Indacaterol 600 μg | Number of Asthma Exacerbations Per Patient (Without Imputation) During the 26 Weeks of the Study | 0.19 Asthma exacerbations | Standard Deviation 0.512 |
| Salmeterol 50 μg | Number of Asthma Exacerbations Per Patient (Without Imputation) During the 26 Weeks of the Study | 0.19 Asthma exacerbations | Standard Deviation 0.494 |
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.
Time frame: 24 hours post-dose at Week 12 + 1 day, Day 85
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at Week 12 + 1 Day, Day 85 | 2.61 Liters | Standard Error 0.023 |
| Indacaterol 600 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at Week 12 + 1 Day, Day 85 | 2.62 Liters | Standard Error 0.023 |
| Salmeterol 50 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at Week 12 + 1 Day, Day 85 | 2.54 Liters | Standard Error 0.023 |