Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, Indacaterol, Salmeterol/fluticasone propionate
Brief summary
The purpose of this study is to compare the effectiveness and safety of indacaterol with salmeterol /fluticasone propionate treatment in patients with moderate chronic obstructive pulmonary disease who, on entry to the study are being treated with salmeterol /fluticasone propionate.
Interventions
DRUGIndacaterol
Indacaterol is delivered via a SDDPI.
DRUGSalmeterol
Salmeterol/fluticasone is delivered via a MDDPI
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
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with moderate COPD (Stage II) * Able to perform spirometry assessments * Current or ex-smokers * On treatment with the fixed-dose combination of salmeterol 50 µg/fluticasone propionate 500 µg MDDPI b.i.d. for the treatment of COPD for ≥ 3 months directly preceding Visit 1.
Exclusion criteria
* Having had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the past year. * Having a history of, or current ECG abnormality * Asthma Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in One Second (FEV1) at 12 Weeks (Imputed With LOCF): Treatment Comparisons | 12 weeks | Spirometry conducted to internationally accepted standards. Trough FEV1 defined as the mean of the FEV1 measurements at 23 h 10 min and 23 h 45 min post the Day 84 morning dose. The primary variable (imputed with last observation carried forward) will be analysed using a mixed model for the Per Protocol Set (PPS). The model will contain treatment as a fixed effect with the baseline FEV1 measurement, FEV1 prior to inhalation and FEV1 10-15 min post inhalation of salbutamol (components of reversibility at Visit 1) as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 12 weeks | FEV1 at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group. |
| FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 26 weeks | FEV1 at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group . |
| FVC Over 26 Weeks of Treatment | 12 and 26 weeks | FVC at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group. |
| Analysis of AUC (5 Min - 4 h) for FEV1 (L) at Week 12 and Week 26: Treatment Comparison | 12 and 26 weeks | The standardized (with respect to the length of time) AUC for FEV1 will be calculated between 5 min and 4 h post morning dose as the sum of trapezoids divided by the length of time at Day 84 (Visit 6) and Day 182 (Visit 10). Scheduled (not actual) time points are to be used. FEV1 measurements taken within 6 h of rescue use will be set to missing before the standardized AUC is calculated. |
| Trough FEV1 (L) at Week 26 (Imputed With LOCF): Treatment Comparisons | 26 weeks | Trough FEV1 is defined as the average of the 23 h 10 min and the 23 h 45 min values taken in the clinic at Visit 11. |
| Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | 26 weeks | The number of exacerbations during the 26 week treatment period will be analyzed using a generalized linear model assuming a negative binomial distribution. |
| Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment | 12 and 26 weeks | The mean daily number of puffs of rescue medication taken by the patient will be derived. If the number of puffs is missing for part of the day (either morning or evening) then a half day will be used in the denominator. Rescue medication data recorded during the 14 day run-in period will be used to calculate the baseline. The mean change from baseline in the daily number of puffs of rescue medication will be analyzed using the same mixed model as specified for the primary analysis, with the baseline FEV1 replaced with the baseline daily rescue use. |
| Rescue Medication Use Over 26 Weeks: Percentage of 'Days With no Rescue Use' | 26 weeks | A 'day with no rescue use' is defined from diary data as any day where the patient has taken no puffs of rescue medication. The percentage of 'days with no rescue use' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'. |
| St Georges Respiratory Questionnaire for COPD | 12 and 26 weeks | A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present. |
| TDI Focal Score at Week 12 and Week 26: Treatment Comparisons | 12 and 26 weeks | The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. |
Countries
Argentina, Colombia, Italy, Malaysia, Mexico, Netherlands, Spain, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol Indacaterol 150 mcg once daily (o.d.) delivered via the Novartis single dose dry power inhaler (SDDPI) (Onbrez® Breezhaler®) | 293 |
| Salmeterol/Fluticasone Propionate Salmeterol 50 mcg /fluticasone propionate 500 mcg for inhalation delivered via a proprietary multi dose dry powder inhaler (MDDPI) device (Seretide® Accuhaler®) twice daily (b.i.d.) | 288 |
| Total | 581 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal Lab reults | 1 | 3 |
| Overall Study | Administrative problems | 8 | 0 |
| Overall Study | Adverse Event | 14 | 14 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 5 | 3 |
| Overall Study | Withdrawal by Subject | 16 | 15 |
Baseline characteristics
| Characteristic | Indacaterol | Salmeterol/Fluticasone Propionate | Total |
|---|---|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 8.39 | 66.8 years STANDARD_DEVIATION 8.53 | 66.0 years STANDARD_DEVIATION 8.49 |
| Sex: Female, Male Female | 89 Participants | 91 Participants | 180 Participants |
| Sex: Female, Male Male | 204 Participants | 197 Participants | 401 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 293 | 85 / 288 |
| serious Total, serious adverse events | 5 / 293 | 17 / 288 |
Outcome results
Primary
Trough Forced Expiratory Volume in One Second (FEV1) at 12 Weeks (Imputed With LOCF): Treatment Comparisons
Spirometry conducted to internationally accepted standards. Trough FEV1 defined as the mean of the FEV1 measurements at 23 h 10 min and 23 h 45 min post the Day 84 morning dose. The primary variable (imputed with last observation carried forward) will be analysed using a mixed model for the Per Protocol Set (PPS). The model will contain treatment as a fixed effect with the baseline FEV1 measurement, FEV1 prior to inhalation and FEV1 10-15 min post inhalation of salbutamol (components of reversibility at Visit 1) as covariates.
Time frame: 12 weeks
Population: full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol | Trough Forced Expiratory Volume in One Second (FEV1) at 12 Weeks (Imputed With LOCF): Treatment Comparisons | 1.591 Liters | Standard Error 0.0276 |
| Salmeterol/Fluticasone Propionate | Trough Forced Expiratory Volume in One Second (FEV1) at 12 Weeks (Imputed With LOCF): Treatment Comparisons | 1.604 Liters | Standard Error 0.0281 |
Secondary
Analysis of AUC (5 Min - 4 h) for FEV1 (L) at Week 12 and Week 26: Treatment Comparison
The standardized (with respect to the length of time) AUC for FEV1 will be calculated between 5 min and 4 h post morning dose as the sum of trapezoids divided by the length of time at Day 84 (Visit 6) and Day 182 (Visit 10). Scheduled (not actual) time points are to be used. FEV1 measurements taken within 6 h of rescue use will be set to missing before the standardized AUC is calculated.
Time frame: 12 and 26 weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol | Analysis of AUC (5 Min - 4 h) for FEV1 (L) at Week 12 and Week 26: Treatment Comparison | Week 12 | 1.689 Liters | Standard Error 0.0201 |
| Indacaterol | Analysis of AUC (5 Min - 4 h) for FEV1 (L) at Week 12 and Week 26: Treatment Comparison | Week 26 | 1.683 Liters | Standard Error 0.0304 |
| Salmeterol/Fluticasone Propionate | Analysis of AUC (5 Min - 4 h) for FEV1 (L) at Week 12 and Week 26: Treatment Comparison | Week 12 | 1.689 Liters | Standard Error 0.0203 |
| Salmeterol/Fluticasone Propionate | Analysis of AUC (5 Min - 4 h) for FEV1 (L) at Week 12 and Week 26: Treatment Comparison | Week 26 | 1.682 Liters | Standard Error 0.031 |
Secondary
FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons
FEV1 at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group.
Time frame: 12 weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 30 min post-dose, | 1.667 Liters | Standard Error 0.0207 |
| Indacaterol | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 23h 10 min post-dose | 1.577 Liters | Standard Error 0.0277 |
| Indacaterol | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 2h post-dose | 1.705 Liters | Standard Error 0.0291 |
| Indacaterol | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 23h 45 min post-dose | 1.597 Liters | Standard Error 0.0283 |
| Indacaterol | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 1h post-dose, | 1.693 Liters | Standard Error 0.0285 |
| Indacaterol | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | -15 min pre-dose | 1.623 Liters | Standard Error 0.0282 |
| Indacaterol | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 4h post-dose | 1.670 Liters | Standard Error 0.0215 |
| Indacaterol | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 5 min post-dose | 1.631 Liters | Standard Error 0.0209 |
| Indacaterol | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | -50 min pre-dose | 1.601 Liters | Standard Error 0.0281 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 5 min post-dose | 1.613 Liters | Standard Error 0.0209 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | -50 min pre-dose | 1.588 Liters | Standard Error 0.0286 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 30 min post-dose, | 1.656 Liters | Standard Error 0.0208 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 1h post-dose, | 1.684 Liters | Standard Error 0.0293 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 2h post-dose | 1.708 Liters | Standard Error 0.03 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 4h post-dose | 1.699 Liters | Standard Error 0.0216 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 23h 10 min post-dose | 1.591 Liters | Standard Error 0.0284 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | 23h 45 min post-dose | 1.613 Liters | Standard Error 0.0291 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons | -15 min pre-dose | 1.616 Liters | Standard Error 0.287 |
Secondary
FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons
FEV1 at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group .
Time frame: 26 weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 30 min post-dose, | 1.670 Liters | Standard Error 0.0244 |
| Indacaterol | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 23h 10 min post-dose | 1.551 Liters | Standard Error 0.0305 |
| Indacaterol | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 2h post-dose | 1.700 Liters | Standard Error 0.0318 |
| Indacaterol | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 23h 45 min post-dose | 1.574 Liters | Standard Error 0.313 |
| Indacaterol | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 1h post-dose, | 1.676 Liters | Standard Error 0.0317 |
| Indacaterol | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | -15 min pre-dose | 1.576 Liters | Standard Error 0.0294 |
| Indacaterol | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 4h post-dose | 1.664 Liters | Standard Error 0.032 |
| Indacaterol | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 5 min post-dose | 1.630 Liters | Standard Error 0.0304 |
| Indacaterol | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | -50 min pre-dose | 1.569 Liters | Standard Error 0.0301 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 5 min post-dose | 1.630 Liters | Standard Error 0.031 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | -50 min pre-dose | 1.582 Liters | Standard Error 0.0304 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 30 min post-dose, | 1.656 Liters | Standard Error 0.0244 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 1h post-dose, | 1.677 Liters | Standard Error 0.0324 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 2h post-dose | 1.693 Liters | Standard Error 0.0325 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 4h post-dose | 1.663 Liters | Standard Error 0.0328 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 23h 10 min post-dose | 1.559 Liters | Standard Error 0.031 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | 23h 45 min post-dose | 1.575 Liters | Standard Error 0.0318 |
| Salmeterol/Fluticasone Propionate | FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons | -15 min pre-dose | 1.595 Liters | Standard Error 0.03 |
Secondary
FVC Over 26 Weeks of Treatment
FVC at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group.
Time frame: 12 and 26 weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol | FVC Over 26 Weeks of Treatment | 12 weeks | 3.090 Liters | Standard Error 0.0457 |
| Indacaterol | FVC Over 26 Weeks of Treatment | 26 weeks | 3.057 Liters | Standard Error 0.0512 |
| Salmeterol/Fluticasone Propionate | FVC Over 26 Weeks of Treatment | 12 weeks | 3.064 Liters | Standard Error 0.0466 |
| Salmeterol/Fluticasone Propionate | FVC Over 26 Weeks of Treatment | 26 weeks | 3.062 Liters | Standard Error 0.052 |
Secondary
Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment
The mean daily number of puffs of rescue medication taken by the patient will be derived. If the number of puffs is missing for part of the day (either morning or evening) then a half day will be used in the denominator. Rescue medication data recorded during the 14 day run-in period will be used to calculate the baseline. The mean change from baseline in the daily number of puffs of rescue medication will be analyzed using the same mixed model as specified for the primary analysis, with the baseline FEV1 replaced with the baseline daily rescue use.
Time frame: 12 and 26 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol | Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment | Baseline | 1.82 number of puffs | Standard Deviation 2.274 |
| Indacaterol | Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment | Week 12 | 1.50 number of puffs | Standard Deviation 1.883 |
| Indacaterol | Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment | Week 26 | 1.37 number of puffs | Standard Deviation 1.775 |
| Salmeterol/Fluticasone Propionate | Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment | Baseline | 1.83 number of puffs | Standard Deviation 2.035 |
| Salmeterol/Fluticasone Propionate | Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment | Week 12 | 1.45 number of puffs | Standard Deviation 1.697 |
| Salmeterol/Fluticasone Propionate | Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment | Week 26 | 1.37 number of puffs | Standard Deviation 1.678 |
Secondary
Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set)
The number of exacerbations during the 26 week treatment period will be analyzed using a generalized linear model assuming a negative binomial distribution.
Time frame: 26 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Indacaterol | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | one | 47 participants |
| Indacaterol | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | three | 2 participants |
| Indacaterol | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | two | 11 participants |
| Indacaterol | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | Greater than or equal to four | 0 participants |
| Indacaterol | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | none | 233 participants |
| Salmeterol/Fluticasone Propionate | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | Greater than or equal to four | 0 participants |
| Salmeterol/Fluticasone Propionate | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | none | 215 participants |
| Salmeterol/Fluticasone Propionate | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | one | 57 participants |
| Salmeterol/Fluticasone Propionate | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | two | 15 participants |
| Salmeterol/Fluticasone Propionate | Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set) | three | 1 participants |
Secondary
Rescue Medication Use Over 26 Weeks: Percentage of 'Days With no Rescue Use'
A 'day with no rescue use' is defined from diary data as any day where the patient has taken no puffs of rescue medication. The percentage of 'days with no rescue use' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol | Rescue Medication Use Over 26 Weeks: Percentage of 'Days With no Rescue Use' | 52.8 % of Days | Standard Error 3.71 |
| Salmeterol/Fluticasone Propionate | Rescue Medication Use Over 26 Weeks: Percentage of 'Days With no Rescue Use' | 54.6 % of Days | Standard Error 3.68 |
Secondary
St Georges Respiratory Questionnaire for COPD
A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.
Time frame: 12 and 26 weeks
Population: Full Analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol | St Georges Respiratory Questionnaire for COPD | Week 12 | 32.8 scores on a scale | Standard Error 1.58 |
| Indacaterol | St Georges Respiratory Questionnaire for COPD | Week 26 | 33.1 scores on a scale | Standard Error 1.87 |
| Salmeterol/Fluticasone Propionate | St Georges Respiratory Questionnaire for COPD | Week 26 | 33.5 scores on a scale | Standard Error 1.93 |
| Salmeterol/Fluticasone Propionate | St Georges Respiratory Questionnaire for COPD | Week 12 | 32.9 scores on a scale | Standard Error 1.61 |
Secondary
TDI Focal Score at Week 12 and Week 26: Treatment Comparisons
The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea.
Time frame: 12 and 26 weeks
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol | TDI Focal Score at Week 12 and Week 26: Treatment Comparisons | 12 weeks | 1.89 Units on a scale | Standard Error 0.499 |
| Indacaterol | TDI Focal Score at Week 12 and Week 26: Treatment Comparisons | 26 weeks | 2.58 Units on a scale | Standard Error 0.543 |
| Salmeterol/Fluticasone Propionate | TDI Focal Score at Week 12 and Week 26: Treatment Comparisons | 12 weeks | 1.69 Units on a scale | Standard Error 0.509 |
| Salmeterol/Fluticasone Propionate | TDI Focal Score at Week 12 and Week 26: Treatment Comparisons | 26 weeks | 2.70 Units on a scale | Standard Error 0.552 |
Secondary
Trough FEV1 (L) at Week 26 (Imputed With LOCF): Treatment Comparisons
Trough FEV1 is defined as the average of the 23 h 10 min and the 23 h 45 min values taken in the clinic at Visit 11.
Time frame: 26 weeks
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol | Trough FEV1 (L) at Week 26 (Imputed With LOCF): Treatment Comparisons | 1.567 Liters | Standard Error 0.0302 |
| Salmeterol/Fluticasone Propionate | Trough FEV1 (L) at Week 26 (Imputed With LOCF): Treatment Comparisons | 1.569 Liters | Standard Error 0.0307 |