COPD
Conditions
Keywords
COPD
Brief summary
To compare the efficacy, safety and pharmacokinetics of QMF149 delivered via Concept1 to salmeterol xinafoate/fluticasone propionate delivered via Accuhaler in adult patients with COPD
Interventions
DRUGQMF149
delivered via Concept1 device
DRUGSalmeterol
delivered via Accuhaler®
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with moderate to very severe COPD (GOLD 2 to GOLD 4) according to the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines * Patients with a post-bronchodilator FEV1 \< 70% of the predicted normal, and a post-bronchodilator FEV1/FVC \< 0.70 at run-in (Visit 101). * Current or ex-smokers who have a smoking history of at least 10 pack years (defined as the number of packs of 20 cigarettes smoked per day multiplied by number of years the patient smoked. e.g.10 pack years = 1 pack /day x 10 yrs, or ½ pack/day x 20 yrs). An ex-smoker may be defined as a subject who has not smoked for ≥ 6 months at screening.
Exclusion criteria
* Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to screening (Visit 1). * Patients who develop a COPD exacerbation between screening (Visit 1) and treatment (Visit 201) will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation. * Patients who have had a respiratory tract infection within 4 weeks prior to screening Visit 1. * Patients who develop a respiratory tract infection between screening (Visit 1) and treatment (Visit 201) will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection. * Patients requiring long term oxygen therapy prescribed for \>12 hours per day. * Patients with, a) any history of asthma or, b) onset of respiratory symptoms prior to age 40 years. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for Trough FEV1 (L) on Day 85 | 12 weeks | Spirometry is conducted according to the global standard. Trough FEV1 is defined as the average of the 23 hour 10 minute and 23 hour 45 minute post dose FEV1 readings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Day 1 through day 85 | — |
| Forced Vital Capacity (FVC) at Each Timepoint | Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85 | Spirometry is conducted according to the global standard. FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84. |
| FEV1/FVC at Each Timepoint | Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85 | Spirometry is conducted according to the global standard. FEV1/FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84. |
| FEV1 (L) on Day 1 Between-treatment Comparisons of AUC (5min - 4h) | Day 1 | Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), Scheduled (not actual) time points are to be used. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. |
| FEV1 AUC (5 Min-4 h), | Day 1(Baseline), Day 28, Day 84 | Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), (5 min-24 h) is measured after the first dose on Day 1 and on Day 28 and Day 84 in a subset of approximately 60 patients. Scheduled (not actual) time points are to be used. The interpretation of FEV1 at time 0 is the baseline value at the randomization visit and the latest pre-dose value (-50 min or -15 min) at subsequent visits. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. The same will be repeated for standardized AUC for FEV1 between 5 min and 24 hours post morning dose. |
| Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for AUC (5 Min - 23 h 45 Min) for FEV1 (L) on Day 28 and Day 84 (Full Analysis Set, 24-h Profiling Subgroup) | Day 28, Day 84 | Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), (5 min-24 h) is measured after the first dose on Day 1 and on Day 28 and Day 84 in a subset of approximately 60 patients. Scheduled (not actual) time points are to be used. The interpretation of FEV1 at time 0 is the baseline value at the randomization visit and the latest pre-dose value (-50 min or -15 min) at subsequent visits. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. The same will be repeated for standardized AUC for FEV1 between 5 min and 24 hours post morning dose. |
| The Usage of Rescue Medication (Short Acting β2-agonist) | 12 weeks | Participants record the number of puffs of rescue medication taken in the previous 12 hours each morning and evening throughout the 12 week treatment period. |
| The Overall Change in Usage of Rescue Medication (Short Acting β2-agonist) . | Baseline to 12 weeks | This value represents the percent of days in the study where no rescue medication was needed. |
| Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | 4 and 12 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. |
| Analysis of the Proportion of Subjects With a Clinically Important Improvement of >=1 Point in the TDI (Transitional Dyspnoea Index)Focal Score by Visit | 4 and 12 weeks | A TDI focal score of ≥1 is considered to be a clinically important improvement from baseline. Analysis of the proportion of subjects with a clinically important improvement of \>=1 point in the TDI focal score, by visit |
| Patient Reported Outcome Measures: COPD Assessment Test | Baseline, 4 and 12 weeks | It consists of eight items, each presented as a semantic 6-point differential scale, providing a total score out of 40. A higher score indicates a worse health status. Scores of 0 - 10, 11 - 20, 21 - 30 and 31 - 40 represent a mild, moderate, severe or very severe clinical impact of COPD upon the patient. |
| Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Baseline, 4 and 12 weeks | Scoring the MOS Sleep Survey is a two-step process:• All items are scored so that a high score reflects more of the attribute implied by the scale name. Each item is converted to a 0 to 100 possible range so that the lowest and highest possible scores are set at 0 and 100, respectively. In this format, scores represent the achieved percentage of the total possible score. For example, a score of 50 represents 50% of the highest possible score. • Second, items within each scale are averaged together to create the 7 scale scores. Scales with at least one item answered can be used to generate a scale score. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Scores represent the average for all items in the scale that the respondent answered. An additional measure is based on the average number of hours sleep each night during the past 4 weeks and are described in outcome measure 15. |
| Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Baseline, 4 and 12 weeks | The sleep quantity subscale,which refers to question 2 of the PRO: On average, how many hours did you sleep each night during the past 4 weeks. More hours of sleep indicate better outcome. |
| Trough FEV1 After First Dose and After 4 Weeks of Treatment | Day 1 and Day 85 | Spirometry is conducted according to the global standard. FEV1 is measured at pre-dose and post dose up to 1 hours on Day 1 and Day 28; 24 hours post-dose on Day 29 and 85. In a subset of approximately 60 patients, FEV1 is measured up to 20 hours postdose on Day 28 and Day 84. |
| Time to First COPD Exacerbation | 12 weeks | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. The reported measure will detail the percentage of participants that were event free of a specified event. |
| Annual Rate of COPD Exacerbations | 12 weeks | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. |
| Duration (in Days) of COPD Exacerbations | 12 weeks | Duration and number of the COPD exacerbation will be analyzed by the negative binomial regression model including treatment, country, smoking status, and COPD severity as factors and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. |
| Percentage of Patients With at Least One Exacerbation up to Week 12 | 12 weeks | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. The reported measure will detail the percentage of participants that had an exacerbation up to week 12. Less exacerbations reflect a better outcome. |
| Time (in Days) to Permanent Study Discontinuation Due to COPD Exacerbation | 12 weeks | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. |
| The Percentage of Patients Who Permanently Discontinued Due to COPD Exacerbation | 12 weeks | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. |
| Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | 12 weeks | Total amount (in doses) of systemic corticosteroid used to treat COPD exacerbation will be summarized descriptively by treatment group per each systemic corticosteroid. |
| Plasma Cortisol Concentrations at Each Timepoint | Day 1, Day 28, Day 84 | Plasma cortisol to be measured in a subset of approximately 60 patients via central laboratory. Blood sample for Plasma cortisol is collected at pre-dose and post dose up to 4 hour on Day 1, up to 12 hours post-dose on Day 28 and Day 84, and 23 hour 35 minute on Day 2, Day 29, and Day 85, and at pre-dose 25 minute on Day 28, and Day 84. |
| Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1, 29, 84 | Plasma indacaterol and mometasone furoate is to be measured in a subset of approximately 60 patients via central laboratory. Blood samples are collected at pre-dose on Day 1, 29, and 84; and post dose up to 4 hour on Day 1, up to 12 hours on Day 28 and 84. For sparse pharmacokinetic testing, blood samples will be collected at 23h 35 min post-dose following morning dose administration on Day 28 and 84, in all patients participating in this study. |
| Pharmacokinetic Parameter: Cmax | Day 28, 84 | Maximum observed plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84. |
| Pharmacokinetic Parameter--Tmax | Day 28, 84 | Time to reach the maximum plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84. |
| Pharmacokinetic Parameter--AUC0-t | Day 28, 84 | Area under the plasma concentration time curve from time zero to time t post-dose is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84. |
| Summary Statistics of COPD Exacerbations over12 Weeks as Defined by Chronic Pulmonary Disease Tool (EXACT) | 12 weeks | The EXACT is a 14-item electronic questionnaire designed to detect the frequency, severity, and duration of exacerbations in patients with COPD. |
Countries
Australia, Belgium, Bulgaria, Denmark, Finland, Germany, Greece, Hong Kong, Hungary, Israel, Malaysia, Poland, Romania, Singapore, South Africa, Spain, Sweden, Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| QMF149 QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | 316 |
| Salmeterol Xinafoate/Fluticasone Propionate Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® | 313 |
| Total | 629 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 11 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-compliance with study treatment | 1 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Terminated by sponsor | 1 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 10 |
Baseline characteristics
| Characteristic | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate | Total |
|---|---|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 7.74 | 64.1 years STANDARD_DEVIATION 7.89 | 64.5 years STANDARD_DEVIATION 7.82 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 32 Participants | 30 Participants | 62 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 9 Participants | 6 Participants | 15 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 273 Participants | 276 Participants | 549 Participants |
| Sex: Female, Male Female | 83 Participants | 86 Participants | 169 Participants |
| Sex: Female, Male Male | 233 Participants | 227 Participants | 460 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / 316 | 83 / 313 |
| serious Total, serious adverse events | 10 / 316 | 19 / 313 |
Outcome results
Primary
Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for Trough FEV1 (L) on Day 85
Spirometry is conducted according to the global standard. Trough FEV1 is defined as the average of the 23 hour 10 minute and 23 hour 45 minute post dose FEV1 readings.
Time frame: 12 weeks
Population: All randomized patients were included in the Full analysis set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for Trough FEV1 (L) on Day 85 | Full analysis set (n=291,282) | 1.270 Liters | Standard Error 0.0124 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for Trough FEV1 (L) on Day 85 | Per protocol set (n=259,251) | 1.277 Liters | Standard Error 0.0136 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for Trough FEV1 (L) on Day 85 | Full analysis set (n=291,282) | 1.215 Liters | Standard Error 0.0124 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for Trough FEV1 (L) on Day 85 | Per protocol set (n=259,251) | 1.228 Liters | Standard Error 0.0137 |
Secondary
Analysis of the Proportion of Subjects With a Clinically Important Improvement of >=1 Point in the TDI (Transitional Dyspnoea Index)Focal Score by Visit
A TDI focal score of ≥1 is considered to be a clinically important improvement from baseline. Analysis of the proportion of subjects with a clinically important improvement of \>=1 point in the TDI focal score, by visit
Time frame: 4 and 12 weeks
Population: Full analysis set, All randomized patients. When data were missing or insufficient for any one of the domains a focal score could not be calculated.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| QMF149 | Analysis of the Proportion of Subjects With a Clinically Important Improvement of >=1 Point in the TDI (Transitional Dyspnoea Index)Focal Score by Visit | Day 28 Change from baseline (n=291,294) | 43.3 (%) showing clinical improvement | 0.1314 |
| QMF149 | Analysis of the Proportion of Subjects With a Clinically Important Improvement of >=1 Point in the TDI (Transitional Dyspnoea Index)Focal Score by Visit | Day 84 Change from baseline (n=287,283) | 52.6 (%) showing clinical improvement | 0.133 |
| Salmeterol Xinafoate/Fluticasone Propionate | Analysis of the Proportion of Subjects With a Clinically Important Improvement of >=1 Point in the TDI (Transitional Dyspnoea Index)Focal Score by Visit | Day 28 Change from baseline (n=291,294) | 40.5 (%) showing clinical improvement | 0.1331 |
| Salmeterol Xinafoate/Fluticasone Propionate | Analysis of the Proportion of Subjects With a Clinically Important Improvement of >=1 Point in the TDI (Transitional Dyspnoea Index)Focal Score by Visit | Day 84 Change from baseline (n=287,283) | 45.9 (%) showing clinical improvement | 0.139 |
Secondary
Annual Rate of COPD Exacerbations
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.
Time frame: 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QMF149 | Annual Rate of COPD Exacerbations | Model based estimates | 0.354 COPD Exacerbations per year |
| QMF149 | Annual Rate of COPD Exacerbations | Actual rate exacerbations per year | 0.39 COPD Exacerbations per year |
| Salmeterol Xinafoate/Fluticasone Propionate | Annual Rate of COPD Exacerbations | Model based estimates | 0.659 COPD Exacerbations per year |
| Salmeterol Xinafoate/Fluticasone Propionate | Annual Rate of COPD Exacerbations | Actual rate exacerbations per year | 0.73 COPD Exacerbations per year |
Secondary
Duration (in Days) of COPD Exacerbations
Duration and number of the COPD exacerbation will be analyzed by the negative binomial regression model including treatment, country, smoking status, and COPD severity as factors and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.
Time frame: 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QMF149 | Duration (in Days) of COPD Exacerbations | 1.4 Days | Standard Deviation 6.59 |
| Salmeterol Xinafoate/Fluticasone Propionate | Duration (in Days) of COPD Exacerbations | 2.0 Days | Standard Deviation 6.28 |
Secondary
FEV1 AUC (5 Min-4 h),
Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), (5 min-24 h) is measured after the first dose on Day 1 and on Day 28 and Day 84 in a subset of approximately 60 patients. Scheduled (not actual) time points are to be used. The interpretation of FEV1 at time 0 is the baseline value at the randomization visit and the latest pre-dose value (-50 min or -15 min) at subsequent visits. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. The same will be repeated for standardized AUC for FEV1 between 5 min and 24 hours post morning dose.
Time frame: Day 1(Baseline), Day 28, Day 84
Population: 24 hr profiling subgroup
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | FEV1 AUC (5 Min-4 h), | Day 1 baseline (n=46,47) | 1.302 Liters*hours | Standard Error 0.0278 |
| QMF149 | FEV1 AUC (5 Min-4 h), | Day 28 (n=45,46) | 1.410 Liters*hours | Standard Error 0.0353 |
| QMF149 | FEV1 AUC (5 Min-4 h), | Day 84 (n=44,46) | 1.387 Liters*hours | Standard Error 0.0401 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1 AUC (5 Min-4 h), | Day 1 baseline (n=46,47) | 1.331 Liters*hours | Standard Error 0.0282 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1 AUC (5 Min-4 h), | Day 28 (n=45,46) | 1.355 Liters*hours | Standard Error 0.0355 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1 AUC (5 Min-4 h), | Day 84 (n=44,46) | 1.372 Liters*hours | Standard Error 0.0401 |
Secondary
FEV1/FVC at Each Timepoint
Spirometry is conducted according to the global standard. FEV1/FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84.
Time frame: Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 4 hr (n=45,44) change | 2.389 FEV1/ FVC (%) | Standard Deviation 3.7079 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 1 / 5 min (n=299, 298) change | 0.488 FEV1/ FVC (%) | Standard Deviation 2.9633 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 1 / 30 min (n=302,306) change | 0.955 FEV1/ FVC (%) | Standard Deviation 3.0166 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 1 / 60 min (n=308,303) change | 1.112 FEV1/ FVC (%) | Standard Deviation 3.1413 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 1 / 4 hr (n=302, 297) change | 1.045 FEV1/ FVC (%) | Standard Deviation 3.3917 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 2 / 23 Hr 10 min (n=297,296) change | 0.503 FEV1/ FVC (%) | Standard Deviation 3.345 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 2 / 23 Hr 45 min (n=307,306) change | 0.583 FEV1/ FVC (%) | Standard Deviation 3.4552 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / -50 min (n=295,296) change | 1.463 FEV1/ FVC (%) | Standard Deviation 3.7864 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / -15 min (n=300,291) change | 1.837 FEV1/ FVC (%) | Standard Deviation 3.9769 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / 5 min (n=297,290) change | 1.951 FEV1/ FVC (%) | Standard Deviation 4.0512 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / 30 min (n=301,291) change | 2.296 FEV1/ FVC (%) | Standard Deviation 4.4904 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / 60 min (n=299,292) change | 2.525 FEV1/ FVC (%) | Standard Deviation 4.3228 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / 4 hr (n=44,45) change | 4.034 FEV1/ FVC (%) | Standard Deviation 5.2622 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / 11hr 10 min (n=47,44) change | 2.553 FEV1/ FVC (%) | Standard Deviation 4.026 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / 16 hr (n=40,41) change | 2.250 FEV1/ FVC (%) | Standard Deviation 3.4006 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / 20 hr (n=43,44) change | 2.535 FEV1/ FVC (%) | Standard Deviation 3.5379 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 29 / 23 hr 10 min (n=293,293) change | 1.771 FEV1/ FVC (%) | Standard Deviation 4.073 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 29 / 23 hr 45 min (n=299,296) change | 2.000 FEV1/ FVC (%) | Standard Deviation 4.0562 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / -50 min (n=295,279) change | 1.449 FEV1/ FVC (%) | Standard Deviation 4.1145 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / -15 min (n=291,286) change | 2.155 FEV1/ FVC (%) | Standard Deviation 4.0673 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 5 min (n=288,280) change | 2.332 FEV1/ FVC (%) | Standard Deviation 4.1032 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 30 min (n=295,281) change | 2.420 FEV1/ FVC (%) | Standard Deviation 4.3561 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 60 min (n=296,282) change | 2.571 FEV1/ FVC (%) | Standard Deviation 4.4128 |
| QMF149 | FEV1/FVC at Each Timepoint | Baseline (n=316, 313) | 46.786 FEV1/ FVC (%) | Standard Deviation 10.0306 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 11hr 10 min (n=45,43) change | 1.944 FEV1/ FVC (%) | Standard Deviation 4.0833 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 11 hr 45 min (n=39,39) change | 2.538 FEV1/ FVC (%) | Standard Deviation 3.7895 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 16 hr (n=41,39) change | 1.415 FEV1/ FVC (%) | Standard Deviation 4.0588 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 20 hr (n=44,43) change | 2.364 FEV1/ FVC (%) | Standard Deviation 4.4315 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 23 hr 10 min (n=302,292) change | 1.856 FEV1/ FVC (%) | Standard Deviation 4.4315 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 84 / 23 hr 45 min (n=301,286) change | 2.098 FEV1/ FVC (%) | Standard Deviation 4.3676 |
| QMF149 | FEV1/FVC at Each Timepoint | Day 28 / 11hr 45 min (n=43,42) change | 2.791 FEV1/ FVC (%) | Standard Deviation 4.1708 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 60 min (n=296,282) change | 2.067 FEV1/ FVC (%) | Standard Deviation 4.3512 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Baseline (n=316, 313) | 46.859 FEV1/ FVC (%) | Standard Deviation 10.0392 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / 20 hr (n=43,44) change | 2.250 FEV1/ FVC (%) | Standard Deviation 3.9935 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 1 / 5 min (n=299, 298) change | 0.047 FEV1/ FVC (%) | Standard Deviation 2.1366 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 16 hr (n=41,39) change | 1.962 FEV1/ FVC (%) | Standard Deviation 3.6981 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 1 / 30 min (n=302,306) change | 0.879 FEV1/ FVC (%) | Standard Deviation 2.7281 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 29 / 23 hr 10 min (n=293,293) change | 1.319 FEV1/ FVC (%) | Standard Deviation 3.82 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 1 / 60 min (n=308,303) change | 1.182 FEV1/ FVC (%) | Standard Deviation 3.0612 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 4 hr (n=45,44) change | 2.682 FEV1/ FVC (%) | Standard Deviation 4.3269 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 1 / 4 hr (n=302, 297) change | 1.397 FEV1/ FVC (%) | Standard Deviation 3.2407 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 29 / 23 hr 45 min (n=299,296) change | 1.566 FEV1/ FVC (%) | Standard Deviation 3.9704 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 2 / 23 Hr 10 min (n=297,296) change | 1.042 FEV1/ FVC (%) | Standard Deviation 3.2074 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 23 hr 10 min (n=302,292) change | 1.414 FEV1/ FVC (%) | Standard Deviation 4.0356 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 2 / 23 Hr 45 min (n=307,306) change | 1.319 FEV1/ FVC (%) | Standard Deviation 3.1977 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / -50 min (n=295,279) change | 1.068 FEV1/ FVC (%) | Standard Deviation 4.1776 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / -50 min (n=295,296) change | 1.140 FEV1/ FVC (%) | Standard Deviation 3.89 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 11hr 10 min (n=45,43) change | 2.105 FEV1/ FVC (%) | Standard Deviation 3.8754 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / -15 min (n=300,291) change | 1.495 FEV1/ FVC (%) | Standard Deviation 3.7597 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / -15 min (n=291,286) change | 1.584 FEV1/ FVC (%) | Standard Deviation 4.3278 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / 5 min (n=297,290) change | 1.581 FEV1/ FVC (%) | Standard Deviation 4.006 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 20 hr (n=44,43) change | 1.837 FEV1/ FVC (%) | Standard Deviation 3.7713 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / 30 min (n=301,291) change | 1.873 FEV1/ FVC (%) | Standard Deviation 4.2723 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 5 min (n=288,280) change | 1.796 FEV1/ FVC (%) | Standard Deviation 4.231 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / 60 min (n=299,292) change | 2.060 FEV1/ FVC (%) | Standard Deviation 4.4398 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 11 hr 45 min (n=39,39) change | 2.295 FEV1/ FVC (%) | Standard Deviation 4.1147 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / 4 hr (n=44,45) change | 2.322 FEV1/ FVC (%) | Standard Deviation 4.0257 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 30 min (n=295,281) change | 2.062 FEV1/ FVC (%) | Standard Deviation 4.3941 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / 11hr 10 min (n=47,44) change | 1.909 FEV1/ FVC (%) | Standard Deviation 3.9389 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / 11hr 45 min (n=43,42) change | 2.476 FEV1/ FVC (%) | Standard Deviation 4.3978 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 84 / 23 hr 45 min (n=301,286) change | 1.593 FEV1/ FVC (%) | Standard Deviation 4.211 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1/FVC at Each Timepoint | Day 28 / 16 hr (n=40,41) change | 2.305 FEV1/ FVC (%) | Standard Deviation 4.3111 |
Secondary
FEV1 (L) on Day 1 Between-treatment Comparisons of AUC (5min - 4h)
Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), Scheduled (not actual) time points are to be used. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment.
Time frame: Day 1
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | FEV1 (L) on Day 1 Between-treatment Comparisons of AUC (5min - 4h) | Day 1 baseline (n=303,311) | 1.142 Liters * hours | Standard Error 0.0233 |
| QMF149 | FEV1 (L) on Day 1 Between-treatment Comparisons of AUC (5min - 4h) | Day 1 post (n=303,311) | 1.277 Liters * hours | Standard Error 0.0086 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1 (L) on Day 1 Between-treatment Comparisons of AUC (5min - 4h) | Day 1 baseline (n=303,311) | 1.169 Liters * hours | Standard Error 0.0259 |
| Salmeterol Xinafoate/Fluticasone Propionate | FEV1 (L) on Day 1 Between-treatment Comparisons of AUC (5min - 4h) | Day 1 post (n=303,311) | 1.260 Liters * hours | Standard Error 0.0085 |
Secondary
Forced Vital Capacity (FVC) at Each Timepoint
Spirometry is conducted according to the global standard. FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84.
Time frame: Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Baseline (n=316,313) | 2.460 liters | Standard Deviation 0.6969 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 1/ 5 min (n=299,298) Change | 0.179 liters | Standard Deviation 0.2165 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 1/ 60 min (n=308,303) Change | 0.222 liters | Standard Deviation 0.2472 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 1/ 4 hr (n=302,297) Change | 0.217 liters | Standard Deviation 0.2847 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 2/ 23hr 10 min (n=297,296) Change | 0.089 liters | Standard Deviation 0.2518 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 2/ 23hr 45 min (n=307,306) Change | 0.083 liters | Standard Deviation 0.2583 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / -50 min (n=295,296) Change | 0.132 liters | Standard Deviation 0.2806 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / -15 min (n=300,291) Change | 0.161 liters | Standard Deviation 0.309 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / 5 min (n=297,290) Change | 0.238 liters | Standard Deviation 0.3163 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / 30 min (n=301,291) Change | 0.263 liters | Standard Deviation 0.3169 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / 60 min (n=299,292) Change | 0.279 liters | Standard Deviation 0.3261 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 29 / 23hr 10 min (n=293,293) Change | 0.121 liters | Standard Deviation 0.2955 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 29 /23hr 45 min (n=299,296) Change | 0.133 liters | Standard Deviation 0.3132 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 /-15 min (n=291,286) Change | 0.144 liters | Standard Deviation 0.3234 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 / 5 min (n=288,290) Change | 0.229 liters | Standard Deviation 0.337 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 /30 min (n=295,281) Change | 0.255 liters | Standard Deviation 0.3344 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 / 60 min (n=296,282) Change | 0.272 liters | Standard Deviation 0.3295 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 85 / 23 hr 10 min (n=302,292) Change | 0.113 liters | Standard Deviation 0.3132 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 85 / 23 hr 45 min (n=301,286) Change | 0.126 liters | Standard Deviation 0.3206 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 1/ 30 min (n=302,306) Change | 0.207 liters | Standard Deviation 0.2279 |
| QMF149 | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 / -50min (n=295,279) Change | 0.125 liters | Standard Deviation 0.2979 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / 60 min (n=299,292) Change | 0.189 liters | Standard Deviation 0.335 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Baseline (n=316,313) | 2.481 liters | Standard Deviation 0.7209 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 /30 min (n=295,281) Change | 0.120 liters | Standard Deviation 0.3537 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 1/ 5 min (n=299,298) Change | 0.060 liters | Standard Deviation 0.1404 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 29 / 23hr 10 min (n=293,293) Change | 0.084 liters | Standard Deviation 0.2817 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 1/ 60 min (n=308,303) Change | 0.152 liters | Standard Deviation 0.2287 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 1/ 30 min (n=302,306) Change | 0.129 liters | Standard Deviation 0.1953 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 1/ 4 hr (n=302,297) Change | 0.183 liters | Standard Deviation 0.2611 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 29 /23hr 45 min (n=299,296) Change | 0.097 liters | Standard Deviation 0.2965 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 2/ 23hr 10 min (n=297,296) Change | 0.092 liters | Standard Deviation 0.2896 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 / -50min (n=295,279) Change | 0.144 liters | Standard Deviation 0.357 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 2/ 23hr 45 min (n=307,306) Change | 0.092 liters | Standard Deviation 0.2815 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 / 60 min (n=296,282) Change | 0.159 liters | Standard Deviation 0.3648 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / -50 min (n=295,296) Change | 0.068 liters | Standard Deviation 0.2814 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 /-15 min (n=291,286) Change | 0.049 liters | Standard Deviation 0.3519 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / -15 min (n=300,291) Change | 0.072 liters | Standard Deviation 0.2892 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 85 / 23 hr 45 min (n=301,286) Change | 0.035 liters | Standard Deviation 0.362 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / 5 min (n=297,290) Change | 0.122 liters | Standard Deviation 0.3068 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 84 / 5 min (n=288,290) Change | 0.076 liters | Standard Deviation 0.3729 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 28 / 30 min (n=301,291) Change | 0.168 liters | Standard Deviation 0.3166 |
| Salmeterol Xinafoate/Fluticasone Propionate | Forced Vital Capacity (FVC) at Each Timepoint | Day 85 / 23 hr 10 min (n=302,292) Change | 0.022 liters | Standard Deviation 0.3482 |
Secondary
Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for AUC (5 Min - 23 h 45 Min) for FEV1 (L) on Day 28 and Day 84 (Full Analysis Set, 24-h Profiling Subgroup)
Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), (5 min-24 h) is measured after the first dose on Day 1 and on Day 28 and Day 84 in a subset of approximately 60 patients. Scheduled (not actual) time points are to be used. The interpretation of FEV1 at time 0 is the baseline value at the randomization visit and the latest pre-dose value (-50 min or -15 min) at subsequent visits. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. The same will be repeated for standardized AUC for FEV1 between 5 min and 24 hours post morning dose.
Time frame: Day 28, Day 84
Population: Peak FEV1 was calculated for all subjects in the FAS at Day 1 (Visit 201) and was calculated for all subjects in the 24-h profiling subset of the FAS at Day 1 (Visit 201), Day 28 (Visit 203) and Day 84 (Visit 205).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for AUC (5 Min - 23 h 45 Min) for FEV1 (L) on Day 28 and Day 84 (Full Analysis Set, 24-h Profiling Subgroup) | Day 28 (n=45,46) | 1.352 Liters*hours | Standard Error 0.0428 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for AUC (5 Min - 23 h 45 Min) for FEV1 (L) on Day 28 and Day 84 (Full Analysis Set, 24-h Profiling Subgroup) | Day 85 (n=47,47) | 1.317 Liters*hours | Standard Error 0.0454 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for AUC (5 Min - 23 h 45 Min) for FEV1 (L) on Day 28 and Day 84 (Full Analysis Set, 24-h Profiling Subgroup) | Day 28 (n=45,46) | 1.298 Liters*hours | Standard Error 0.0431 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for AUC (5 Min - 23 h 45 Min) for FEV1 (L) on Day 28 and Day 84 (Full Analysis Set, 24-h Profiling Subgroup) | Day 85 (n=47,47) | 1.303 Liters*hours | Standard Error 0.0459 |
Secondary
Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint
Time frame: Day 1 through day 85
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 1/5min (n=290,298) | 1.254 liter | Standard Error 0.0069 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 1/30 min (n=294,306) | 1.281 liter | Standard Error 0.0079 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 1/60min (n=300,303) | 1.281 liter | Standard Error 0.0087 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 2/ 23 hr 10 min (n=288,295) | 1.213 liter | Standard Error 0.0108 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 2/ 23 hr 45 min (n=297,305) | 1.215 liter | Standard Error 0.0106 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ -50min (n=288,295) | 1.265 liter | Standard Error 0.0132 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ -15min (n=292,290) | 1.287 liter | Standard Error 0.0132 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ 5min (n=290,289) | 1.329 liter | Standard Error 0.0113 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ 30min (n=293,290) | 1.352 liter | Standard Error 0.0118 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ 60min (n=292,290) | 1.353 liter | Standard Error 0.0123 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 29/ 23 hr 45 min (n=290,295) | 1.281 liter | Standard Error 0.0123 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ -50 min (n=286,278) | 1.259 liter | Standard Error 0.014 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ -15 min (n=282,285) | 1.282 liter | Standard Error 0.0146 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 5 min (n=280,279) | 1.336 liter | Standard Error 0.0128 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 30 min (n=286,280) | 1.352 liter | Standard Error 0.0124 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 60 min (n=287,281) | 1.351 liter | Standard Error 0.0128 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 23 hr 10 min (n=292,291) | 1.264 liter | Standard Error 0.0125 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 23 hr 45 min (n=291,285) | 1.273 liter | Standard Error 0.0125 |
| QMF149 | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 29/ 23 hr 10 min (n=285,292) | 1.269 liter | Standard Error 0.0118 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 29/ 23 hr 10 min (n=285,292) | 1.242 liter | Standard Error 0.0117 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 1/5min (n=290,298) | 1.198 liter | Standard Error 0.0068 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 30 min (n=286,280) | 1.277 liter | Standard Error 0.0124 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 1/30 min (n=294,306) | 1.250 liter | Standard Error 0.0087 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 29/ 23 hr 45 min (n=290,295) | 1.254 liter | Standard Error 0.0122 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 1/60min (n=300,303) | 1.256 liter | Standard Error 0.0087 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ 60min (n=292,290) | 1.298 liter | Standard Error 0.0122 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 2/ 23 hr 10 min (n=288,295) | 1.239 liter | Standard Error 0.0107 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ -50 min (n=286,278) | 1.195 liter | Standard Error 0.0141 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 2/ 23 hr 45 min (n=297,305) | 1.244 liter | Standard Error 0.0105 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 60 min (n=287,281) | 1.283 liter | Standard Error 0.0128 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ -50min (n=288,295) | 1.287 liter | Standard Error 0.0139 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ -15 min (n=282,285) | 1.222 liter | Standard Error 0.0147 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ -15min (n=292,290) | 1.235 liter | Standard Error 0.014 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 23 hr 45 min (n=291,285) | 1.221 liter | Standard Error 0.0126 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ 5min (n=290,289) | 1.268 liter | Standard Error 0.0113 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 5 min (n=280,279) | 1.243 liter | Standard Error 0.0128 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 28/ 30min (n=293,290) | 1.298 liter | Standard Error 0.0118 |
| Salmeterol Xinafoate/Fluticasone Propionate | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint | Absolute Value Day 84/ 23 hr 10 min (n=292,291) | 1.212 liter | Standard Error 0.0125 |
Secondary
Patient Reported Outcome Measures: COPD Assessment Test
It consists of eight items, each presented as a semantic 6-point differential scale, providing a total score out of 40. A higher score indicates a worse health status. Scores of 0 - 10, 11 - 20, 21 - 30 and 31 - 40 represent a mild, moderate, severe or very severe clinical impact of COPD upon the patient.
Time frame: Baseline, 4 and 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Patient Reported Outcome Measures: COPD Assessment Test | Day 28 Post (n=303,298) | 15.8 Units on a scale | Standard Deviation 7.63 |
| QMF149 | Patient Reported Outcome Measures: COPD Assessment Test | Day 84 Baseline (n=295,285) | 15.9 Units on a scale | Standard Deviation 7.54 |
| QMF149 | Patient Reported Outcome Measures: COPD Assessment Test | Day 28 baseline (n=303,298) | 16.2 Units on a scale | Standard Deviation 7.58 |
| QMF149 | Patient Reported Outcome Measures: COPD Assessment Test | Day 84 Post (n=295,285) | 15.5 Units on a scale | Standard Deviation 7.56 |
| QMF149 | Patient Reported Outcome Measures: COPD Assessment Test | Day 28 Change (n=303,298) | -0.4 Units on a scale | Standard Deviation 5.56 |
| QMF149 | Patient Reported Outcome Measures: COPD Assessment Test | Day 84 change (n=295,285) | -0.4 Units on a scale | Standard Deviation 5.77 |
| QMF149 | Patient Reported Outcome Measures: COPD Assessment Test | Baseline (n= 311,308) | 16.3 Units on a scale | Standard Deviation 7.6 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: COPD Assessment Test | Day 84 change (n=295,285) | 0.2 Units on a scale | Standard Deviation 5.84 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: COPD Assessment Test | Baseline (n= 311,308) | 16.2 Units on a scale | Standard Deviation 7.48 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: COPD Assessment Test | Day 28 baseline (n=303,298) | 16.2 Units on a scale | Standard Deviation 7.48 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: COPD Assessment Test | Day 28 Post (n=303,298) | 16.8 Units on a scale | Standard Deviation 7.75 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: COPD Assessment Test | Day 28 Change (n=303,298) | 0.6 Units on a scale | Standard Deviation 4.94 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: COPD Assessment Test | Day 84 Baseline (n=295,285) | 16.1 Units on a scale | Standard Deviation 8.38 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: COPD Assessment Test | Day 84 Post (n=295,285) | 16.3 Units on a scale | Standard Deviation 8.38 |
Secondary
Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale
The sleep quantity subscale,which refers to question 2 of the PRO: On average, how many hours did you sleep each night during the past 4 weeks. More hours of sleep indicate better outcome.
Time frame: Baseline, 4 and 12 weeks
Population: Full analysis set.Higher scores show better outcomes.Excepting the sleep quantity subscale,scoring the MOS requires two steps:(a) assigning a point value to each response and (b) summing the point values for all the items in a given subscale or index. Each subscale and index score is then converted to a T score with a mean of 50 and an SD of 10.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Post D28(n=292,285) | 6.5717 hours of sleep | Standard Deviation 1.54708 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Baseline D84(n=285,274) | 6.5456 hours of sleep | Standard Deviation 1.42402 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Baseline D28(n=292,285) | 6.5702 hours of sleep | Standard Deviation 1.44879 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Post D84(n=285,274) | 6.5561 hours of sleep | Standard Deviation 1.4378 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Change D28(n=292,285) | 0.0015 hours of sleep | Standard Deviation 1.0739 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Change D84(n=285,274) | 0.0105 hours of sleep | Standard Deviation 1.1227 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Baseline (n=301,295) | 6.5565 hours of sleep | Standard Deviation 1.44169 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Change D84(n=285,274) | 0.0073 hours of sleep | Standard Deviation 1.18906 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Baseline (n=301,295) | 6.6203 hours of sleep | Standard Deviation 1.34895 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Baseline D28(n=292,285) | 6.6351 hours of sleep | Standard Deviation 1.35775 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Post D28(n=292,285) | 6.6246 hours of sleep | Standard Deviation 1.46356 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Change D28(n=292,285) | -0.0105 hours of sleep | Standard Deviation 1.10691 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Baseline D84(n=285,274) | 6.6496 hours of sleep | Standard Deviation 1.345 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale | Sleep quantity Post D84(n=285,274) | 6.6569 hours of sleep | Standard Deviation 1.37648 |
Secondary
Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale
Scoring the MOS Sleep Survey is a two-step process:• All items are scored so that a high score reflects more of the attribute implied by the scale name. Each item is converted to a 0 to 100 possible range so that the lowest and highest possible scores are set at 0 and 100, respectively. In this format, scores represent the achieved percentage of the total possible score. For example, a score of 50 represents 50% of the highest possible score. • Second, items within each scale are averaged together to create the 7 scale scores. Scales with at least one item answered can be used to generate a scale score. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Scores represent the average for all items in the scale that the respondent answered. An additional measure is based on the average number of hours sleep each night during the past 4 weeks and are described in outcome measure 15.
Time frame: Baseline, 4 and 12 weeks
Population: Full analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 28 post (n=290,285) | 50.9323 Units on a scale | Standard Deviation 8.9254 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy baseline D 84 (n=284,274) | 55.2125 Units on a scale | Standard Deviation 9.81055 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 84 change (n=283,274) | 0.6177 Units on a scale | Standard Deviation 7.42456 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy Post D 84 (n=284,274) | 55.2467 Units on a scale | Standard Deviation 10.00283 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Baseline (n=299,295) | 48.8815 Units on a scale | Standard Deviation 9.32313 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy change D 84 (n=284,274) | 0.0342 Units on a scale | Standard Deviation 8.81793 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath Baseline (n=302,295) | 44.5221 Units on a scale | Standard Deviation 13.28329 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence baseline (n=302,296) | 47.6646 Units on a scale | Standard Deviation 9.56376 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 84 Baseline (n=283,274) | 49.7622 Units on a scale | Standard Deviation 8.611 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence baseline D28 (n=290,285) | 47.8711 Units on a scale | Standard Deviation 9.4894 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 28 Bseline(n=293,285) | 44.6348 Units on a scale | Standard Deviation 13.1571 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence post D28 (n=290,285) | 48.4429 Units on a scale | Standard Deviation 9.93046 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 28 Baseline (n=290,285) | 48.8234 Units on a scale | Standard Deviation 9.40239 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence change D28 (n=290,285) | 0.5718 Units on a scale | Standard Deviation 7.91162 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 28 post (n=293,285) | 45.8814 Units on a scale | Standard Deviation 11.85664 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence baseline D84 (n=284,274) | 47.7821 Units on a scale | Standard Deviation 9.53639 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Baseline (n=299,295) | 49.6423 Units on a scale | Standard Deviation 8.50059 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence post D84 (n=284,274) | 48.2568 Units on a scale | Standard Deviation 10.36223 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 28 change (n=293,285) | 1.2466 Units on a scale | Standard Deviation 12.21272 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence change D84 (n=284,274) | 0.4747 Units on a scale | Standard Deviation 8.11292 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 28 Post (n=290,285) | 49.3476 Units on a scale | Standard Deviation 9.37744 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Baseline (n=300,295) | 50.4795 Units on a scale | Standard Deviation 9.72203 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 84 Bseline (n=287,274) | 44.8645 Units on a scale | Standard Deviation 12.99605 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Baseline D28 (n=290,285) | 50.6034 Units on a scale | Standard Deviation 9.67464 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 84 Post (n=283,274) | 50.7508 Units on a scale | Standard Deviation 9.22016 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Post D28 (n=290,285) | 51.4799 Units on a scale | Standard Deviation 9.86137 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 84 post (n=287,274) | 45.7676 Units on a scale | Standard Deviation 13.20151 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Change D28 (n=290,285) | 0.8764 Units on a scale | Standard Deviation 7.0396 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 28 change(n=290,285) | 0.5241 Units on a scale | Standard Deviation 6.70023 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Baseline D84 (n=284,274) | 50.7327 Units on a scale | Standard Deviation 9.64776 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 84 change (n=287,274) | 0.9031 Units on a scale | Standard Deviation 12.11351 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Post D84 (n=284,274) | 51.3590 Units on a scale | Standard Deviation 10.16584 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 28 change (n=290,285) | 1.2490 Units on a scale | Standard Deviation 5.67591 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Change D84 (n=284,274) | 0.6263 Units on a scale | Standard Deviation 7.22742 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy baseline (n=300,295) | 54.9999 Units on a scale | Standard Deviation 9.85865 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 baseline (n=299,295) | 50.4610 Units on a scale | Standard Deviation 9.14154 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 84 Baseline (n=283,274) | 48.8414 Units on a scale | Standard Deviation 9.29113 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 baseline D 28 (n=289,285) | 50.5720 Units on a scale | Standard Deviation 9.15508 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy baseline D 28 (n=291,285) | 55.0531 Units on a scale | Standard Deviation 9.80609 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Post D 28 (n=289,285) | 51.5578 Units on a scale | Standard Deviation 9.43365 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 84 Change (n=283,274) | 0.9887 Units on a scale | Standard Deviation 6.52972 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Change D 28 (n=289,285) | 0.9858 Units on a scale | Standard Deviation 6.00711 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy Post D 28 (n=291,285) | 55.2032 Units on a scale | Standard Deviation 10.04281 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Baseline D 84 (n=283,274) | 50.6880 Units on a scale | Standard Deviation 9.16092 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 84 post (n=283,274) | 49.4591 Units on a scale | Standard Deviation 9.29113 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Post D 84 (n=283,274) | 51.4615 Units on a scale | Standard Deviation 9.79518 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy Change D 28 (n=291,285) | 0.1501 Units on a scale | Standard Deviation 9.8392 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Change D 84 (n=283,274) | 0.7735 Units on a scale | Standard Deviation 6.66709 |
| QMF149 | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 28 Baseline (n=290,285) | 49.6833 Units on a scale | Standard Deviation 8.57069 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Change D 84 (n=283,274) | 0.2663 Units on a scale | Standard Deviation 6.29393 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 28 Baseline (n=290,285) | 49.7616 Units on a scale | Standard Deviation 8.49307 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Baseline (n=299,295) | 49.9292 Units on a scale | Standard Deviation 8.5133 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 28 post (n=290,285) | 50.0858 Units on a scale | Standard Deviation 8.7711 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 28 change (n=290,285) | 0.3242 Units on a scale | Standard Deviation 6.63156 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 84 Baseline (n=283,274) | 49.6634 Units on a scale | Standard Deviation 8.41228 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 84 Post (n=283,274) | 50.2380 Units on a scale | Standard Deviation 9.07204 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep disturbance Day 84 Change (n=283,274) | 0.5745 Units on a scale | Standard Deviation 6.45362 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Baseline (n=299,295) | 49.8895 Units on a scale | Standard Deviation 9.18885 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 28 Baseline (n=290,285) | 49.7733 Units on a scale | Standard Deviation 9.2303 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 28 Post (n=290,285) | 49.5067 Units on a scale | Standard Deviation 9.39012 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 28 change(n=290,285) | -0.2667 Units on a scale | Standard Deviation 7.06825 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 84 Baseline (n=283,274) | 49.6385 Units on a scale | Standard Deviation 9.19681 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 84 post (n=283,274) | 49.6108 Units on a scale | Standard Deviation 9.51632 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep snoring Day 84 change (n=283,274) | -0.0277 Units on a scale | Standard Deviation 8.266668 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath Baseline (n=302,295) | 45.4259 Units on a scale | Standard Deviation 11.5156 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 28 Bseline(n=293,285) | 45.3292 Units on a scale | Standard Deviation 11.48556 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 28 post (n=293,285) | 45.5774 Units on a scale | Standard Deviation 11.65379 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 28 change (n=293,285) | 0.2481 Units on a scale | Standard Deviation 11.44262 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 84 Bseline (n=287,274) | 45.3180 Units on a scale | Standard Deviation 11.37006 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 84 post (n=287,274) | 45.7049 Units on a scale | Standard Deviation 11.8491 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep shortness of breath D 84 change (n=287,274) | 0.3870 Units on a scale | Standard Deviation 10.97093 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy baseline (n=300,295) | 54.9725 Units on a scale | Standard Deviation 9.41704 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy baseline D 28 (n=291,285) | 55.0679 Units on a scale | Standard Deviation 9.30955 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy Post D 28 (n=291,285) | 54.8296 Units on a scale | Standard Deviation 10.21011 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy Change D 28 (n=291,285) | -0.2383 Units on a scale | Standard Deviation 9.2125 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy baseline D 84 (n=284,274) | 55.1084 Units on a scale | Standard Deviation 9.20723 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy Post D 84 (n=284,274) | 54.5424 Units on a scale | Standard Deviation 9.96705 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep adequacy change D 84 (n=284,274) | -0.5659 Units on a scale | Standard Deviation 8.578 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence baseline (n=302,296) | 49.1709 Units on a scale | Standard Deviation 9.56807 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence baseline D28 (n=290,285) | 49.1092 Units on a scale | Standard Deviation 9.58808 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence post D28 (n=290,285) | 48.6761 Units on a scale | Standard Deviation 10.1785 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence change D28 (n=290,285) | -0.4331 Units on a scale | Standard Deviation 8.67719 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence baseline D84 (n=284,274) | 48.9335 Units on a scale | Standard Deviation 9.55603 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence post D84 (n=284,274) | 49.0461 Units on a scale | Standard Deviation 9.54132 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep somnolence change D84 (n=284,274) | 0.1126 Units on a scale | Standard Deviation 7.83662 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Baseline (n=300,295) | 50.8382 Units on a scale | Standard Deviation 9.16082 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Baseline D28 (n=290,285) | 50.7911 Units on a scale | Standard Deviation 9.13425 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Post D28 (n=290,285) | 50.7836 Units on a scale | Standard Deviation 10.02742 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Change D28 (n=290,285) | -0.0074 Units on a scale | Standard Deviation 7.73909 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Baseline D84 (n=284,274) | 50.6951 Units on a scale | Standard Deviation 9.09626 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Post D84 (n=284,274) | 50.9888 Units on a scale | Standard Deviation 9.54642 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 1 Change D84 (n=284,274) | 0.2938 Units on a scale | Standard Deviation 7.08082 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 baseline (n=299,295) | 51.0701 Units on a scale | Standard Deviation 8.62899 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 baseline D 28 (n=289,285) | 50.9923 Units on a scale | Standard Deviation 8.60656 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Post D 28 (n=289,285) | 51.0116 Units on a scale | Standard Deviation 9.33837 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Change D 28 (n=289,285) | 0.0193 Units on a scale | Standard Deviation 6.99119 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Baseline D 84 (n=283,274) | 50.8848 Units on a scale | Standard Deviation 8.58893 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale | Sleep Problems Index 2 Post D 84 (n=283,274) | 51.1511 Units on a scale | Standard Deviation 9.09673 |
Secondary
Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire)
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: 4 and 12 weeks
Population: Full analysis set : At baseline all subjects with a baseline value are included. At each post-baseline day, only subjects with a value at both baseline and the respective day are included. Baseline SGRQ was completed on Day 1 prior to first dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 28 Post (n=304,295) | 40.95 Total Score | Standard Deviation 18.527 |
| QMF149 | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 84 Baseline (n=297,284) | 42.57 Total Score | Standard Deviation 18.322 |
| QMF149 | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 28 Baseline (n=304,295) | 42.87 Total Score | Standard Deviation 18.392 |
| QMF149 | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 84 Post (n=297,284) | 39.81 Total Score | Standard Deviation 19.057 |
| QMF149 | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 28 Change (n=304,295) | -1.92 Total Score | Standard Deviation 11.383 |
| QMF149 | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 84 Change (n=297,284) | -2.76 Total Score | Standard Deviation 13.062 |
| QMF149 | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Baseline (n=314, 308) | 43.05 Total Score | Standard Deviation 18.515 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 84 Change (n=297,284) | -1.02 Total Score | Standard Deviation 12.178 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Baseline (n=314, 308) | 42.28 Total Score | Standard Deviation 17.941 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 28 Baseline (n=304,295) | 42.47 Total Score | Standard Deviation 18.051 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 28 Post (n=304,295) | 42.18 Total Score | Standard Deviation 18.101 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 28 Change (n=304,295) | -0.29 Total Score | Standard Deviation 12.145 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 84 Baseline (n=297,284) | 42.03 Total Score | Standard Deviation 18.099 |
| Salmeterol Xinafoate/Fluticasone Propionate | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) | Day 84 Post (n=297,284) | 41.01 Total Score | Standard Deviation 18.553 |
Secondary
Percentage of Patients With at Least One Exacerbation up to Week 12
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. The reported measure will detail the percentage of participants that had an exacerbation up to week 12. Less exacerbations reflect a better outcome.
Time frame: 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QMF149 | Percentage of Patients With at Least One Exacerbation up to Week 12 | 7.6 Percentage of participants |
| Salmeterol Xinafoate/Fluticasone Propionate | Percentage of Patients With at Least One Exacerbation up to Week 12 | 14.1 Percentage of participants |
Secondary
Pharmacokinetic Parameter--AUC0-t
Area under the plasma concentration time curve from time zero to time t post-dose is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.
Time frame: Day 28, 84
Population: Moderate PK set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Pharmacokinetic Parameter--AUC0-t | 28 Days (n=35,36) | 653 hr*pg/mL | Standard Deviation 296 |
| QMF149 | Pharmacokinetic Parameter--AUC0-t | 84 Days (n=31,33) | 693 hr*pg/mL | Standard Deviation 297 |
| Salmeterol Xinafoate/Fluticasone Propionate | Pharmacokinetic Parameter--AUC0-t | 28 Days (n=35,36) | 2400 hr*pg/mL | Standard Deviation 771 |
| Salmeterol Xinafoate/Fluticasone Propionate | Pharmacokinetic Parameter--AUC0-t | 84 Days (n=31,33) | 2760 hr*pg/mL | Standard Deviation 802 |
Secondary
Pharmacokinetic Parameter: Cmax
Maximum observed plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.
Time frame: Day 28, 84
Population: Moderate PK set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Pharmacokinetic Parameter: Cmax | Day 28 (n=36,35) | 73.3 pg/mL | Standard Deviation 24.9 |
| QMF149 | Pharmacokinetic Parameter: Cmax | Day 84 (n=32,35) | 80.2 pg/mL | Standard Deviation 23 |
| Salmeterol Xinafoate/Fluticasone Propionate | Pharmacokinetic Parameter: Cmax | Day 28 (n=36,35) | 215 pg/mL | Standard Deviation 71.5 |
| Salmeterol Xinafoate/Fluticasone Propionate | Pharmacokinetic Parameter: Cmax | Day 84 (n=32,35) | 263 pg/mL | Standard Deviation 101 |
Secondary
Pharmacokinetic Parameter--Tmax
Time to reach the maximum plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.
Time frame: Day 28, 84
Population: Moderate PK set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Pharmacokinetic Parameter--Tmax | Day 28 (n= 36 ,35) | 0.250 Hr | Full Range 0.833 |
| QMF149 | Pharmacokinetic Parameter--Tmax | Day 84 (n= 32 ,35) | 0.250 Hr | Full Range 1.92 |
| Salmeterol Xinafoate/Fluticasone Propionate | Pharmacokinetic Parameter--Tmax | Day 28 (n= 36 ,35) | 0.970 Hr | Full Range 0.662 |
| Salmeterol Xinafoate/Fluticasone Propionate | Pharmacokinetic Parameter--Tmax | Day 84 (n= 32 ,35) | 1.00 Hr | Full Range 1.92 |
Secondary
Plasma Cortisol Concentrations at Each Timepoint
Plasma cortisol to be measured in a subset of approximately 60 patients via central laboratory. Blood sample for Plasma cortisol is collected at pre-dose and post dose up to 4 hour on Day 1, up to 12 hours post-dose on Day 28 and Day 84, and 23 hour 35 minute on Day 2, Day 29, and Day 85, and at pre-dose 25 minute on Day 28, and Day 84.
Time frame: Day 1, Day 28, Day 84
Population: Safety set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 1 / 15 min (n=44,41) | 284.0 nmol/mL | Standard Deviation 151.96 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 28 / 11hr 35 min (n=40,37) | 124.8 nmol/mL | Standard Deviation 71.71 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 28/-25min (n=40,39) | 342.1 nmol/mL | Standard Deviation 160.16 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 28/ 23 hr 35 min (n=33,32) | 310.6 nmol/mL | Standard Deviation 99.81 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 1/ 4 hr (n=44,38) | 247.6 nmol/mL | Standard Deviation 85.9 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 84 /-25 min (n=41,37) | 337.4 nmol/mL | Standard Deviation 155.24 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 28 / 15 min (n=40,39) | 275.0 nmol/mL | Standard Deviation 140.83 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 84/ 15 min (n=40,36) | 291.1 nmol/mL | Standard Deviation 144.26 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 1 / 1 hr (n=44,41) | 249.1 nmol/mL | Standard Deviation 144.9 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 84/ 60 min (n=41,38) | 271.3 nmol/mL | Standard Deviation 158.88 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 28 / 1 hr (n=40,39) | 255.9 nmol/mL | Standard Deviation 134.26 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 84/ 4 hr (n=41,38) | 268.4 nmol/mL | Standard Deviation 136.22 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 1 /23 hr 35 min (n=38,37) | 295.9 nmol/mL | Standard Deviation 153.8 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 84/ 11 hr 35 min (n=41,35) | 152.0 nmol/mL | Standard Deviation 99.66 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 28 / 4hr (n=40,38) | 241.9 nmol/mL | Standard Deviation 89.07 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Day 84 / 23 hr 35 min (n=37,36) | 339.9 nmol/mL | Standard Deviation 159.51 |
| QMF149 | Plasma Cortisol Concentrations at Each Timepoint | Baseline (n=45,41) | 328.5 nmol/mL | Standard Deviation 149.56 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 84 / 23 hr 35 min (n=37,36) | 315.9 nmol/mL | Standard Deviation 104.67 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Baseline (n=45,41) | 300.2 nmol/mL | Standard Deviation 107.36 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 1 / 15 min (n=44,41) | 247.1 nmol/mL | Standard Deviation 91.99 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 1 / 1 hr (n=44,41) | 223.0 nmol/mL | Standard Deviation 85.93 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 1/ 4 hr (n=44,38) | 205.7 nmol/mL | Standard Deviation 68.65 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 1 /23 hr 35 min (n=38,37) | 274.2 nmol/mL | Standard Deviation 115.33 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 28/-25min (n=40,39) | 295.6 nmol/mL | Standard Deviation 98.78 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 28 / 15 min (n=40,39) | 239.8 nmol/mL | Standard Deviation 90.14 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 28 / 1 hr (n=40,39) | 211.9 nmol/mL | Standard Deviation 89.41 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 28 / 4hr (n=40,38) | 203.6 nmol/mL | Standard Deviation 108.62 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 28 / 11hr 35 min (n=40,37) | 124.1 nmol/mL | Standard Deviation 72.39 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 28/ 23 hr 35 min (n=33,32) | 306.5 nmol/mL | Standard Deviation 119.33 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 84 /-25 min (n=41,37) | 324.1 nmol/mL | Standard Deviation 104.01 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 84/ 15 min (n=40,36) | 265.5 nmol/mL | Standard Deviation 103.39 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 84/ 60 min (n=41,38) | 236.3 nmol/mL | Standard Deviation 104.06 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 84/ 4 hr (n=41,38) | 224.2 nmol/mL | Standard Deviation 100.36 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Cortisol Concentrations at Each Timepoint | Day 84/ 11 hr 35 min (n=41,35) | 147.5 nmol/mL | Standard Deviation 108.21 |
Secondary
Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint
Plasma indacaterol and mometasone furoate is to be measured in a subset of approximately 60 patients via central laboratory. Blood samples are collected at pre-dose on Day 1, 29, and 84; and post dose up to 4 hour on Day 1, up to 12 hours on Day 28 and 84. For sparse pharmacokinetic testing, blood samples will be collected at 23h 35 min post-dose following morning dose administration on Day 28 and 84, in all patients participating in this study.
Time frame: Day 1, 29, 84
Population: Moderate PK set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1 / 15 min (n=44,45) | 31.4 pg/mL | Standard Deviation 17.9 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 / 11hr 35 min (n=41,42) | 19.2 pg/mL | Standard Deviation 12.6 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 0 time (n=41,42) | 14.5 pg/mL | Standard Deviation 18 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28/ 23 hr 35 min (n=45,46) | 10.8 pg/mL | Standard Deviation 7.32 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1/ 4 hr (n=43,45) | 26.8 pg/mL | Standard Deviation 15.6 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84 0 time (n=39,40) | 23.1 pg/mL | Standard Deviation 30.5 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 / 15 min (n= 42,43) | 57.5 pg/mL | Standard Deviation 31.6 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84/ 15 min (n=38,40) | 68.1 pg/mL | Standard Deviation 41.4 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1 / 1 hr (n=43,45) | 44.6 pg/mL | Standard Deviation 19.3 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84/ 60 min (n=38,40) | 84.2 pg/mL | Standard Deviation 40.6 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 / 1 hr (n=41,42) | 68.4 pg/mL | Standard Deviation 35 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84/ 4 hr (n=40,40) | 49.9 pg/mL | Standard Deviation 26.4 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1 /23 hr 35 min (n=37, 38) | 13.1 pg/mL | Standard Deviation 16.7 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84/ 11 hr 35 min (n=39,41) | 25.9 pg/mL | Standard Deviation 21.2 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 / 4hr (n=42,42) | 43.7 pg/mL | Standard Deviation 25.7 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84 / 23 hr 35 min (n=44,45) | 14.6 pg/mL | Standard Deviation 17.8 |
| QMF149 | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1 time 0 (n=34,44) | 4.17 pg/mL | Standard Deviation 13.8 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84 / 23 hr 35 min (n=44,45) | 98.7 pg/mL | Standard Deviation 67.8 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1 time 0 (n=34,44) | 4.32 pg/mL | Standard Deviation 12.3 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1 / 15 min (n=44,45) | 111 pg/mL | Standard Deviation 52.1 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1 / 1 hr (n=43,45) | 89.7 pg/mL | Standard Deviation 41.2 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1/ 4 hr (n=43,45) | 51.4 pg/mL | Standard Deviation 33.5 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 1 /23 hr 35 min (n=37, 38) | 44.8 pg/mL | Standard Deviation 69.9 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 0 time (n=41,42) | 82.0 pg/mL | Standard Deviation 47.4 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 / 15 min (n= 42,43) | 213 pg/mL | Standard Deviation 98 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 / 1 hr (n=41,42) | 194 pg/mL | Standard Deviation 99 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 / 4hr (n=42,42) | 132 pg/mL | Standard Deviation 67.9 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28 / 11hr 35 min (n=41,42) | 86.6 pg/mL | Standard Deviation 40.4 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 28/ 23 hr 35 min (n=45,46) | 76.5 pg/mL | Standard Deviation 38.1 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84 0 time (n=39,40) | 101 pg/mL | Standard Deviation 50.8 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84/ 15 min (n=38,40) | 255 pg/mL | Standard Deviation 129 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84/ 60 min (n=38,40) | 241 pg/mL | Standard Deviation 119 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84/ 4 hr (n=40,40) | 161 pg/mL | Standard Deviation 84.6 |
| Salmeterol Xinafoate/Fluticasone Propionate | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint | Day 84/ 11 hr 35 min (n=39,41) | 115 pg/mL | Standard Deviation 67.5 |
Secondary
Summary Statistics of COPD Exacerbations over12 Weeks as Defined by Chronic Pulmonary Disease Tool (EXACT)
The EXACT is a 14-item electronic questionnaire designed to detect the frequency, severity, and duration of exacerbations in patients with COPD.
Time frame: 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QMF149 | Summary Statistics of COPD Exacerbations over12 Weeks as Defined by Chronic Pulmonary Disease Tool (EXACT) | 0.2 COPD exacerbation per participant | Standard Deviation 0.49 |
| Salmeterol Xinafoate/Fluticasone Propionate | Summary Statistics of COPD Exacerbations over12 Weeks as Defined by Chronic Pulmonary Disease Tool (EXACT) | 0.3 COPD exacerbation per participant | Standard Deviation 0.56 |
Secondary
The Overall Change in Usage of Rescue Medication (Short Acting β2-agonist) .
This value represents the percent of days in the study where no rescue medication was needed.
Time frame: Baseline to 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QMF149 | The Overall Change in Usage of Rescue Medication (Short Acting β2-agonist) . | 8.796 % of days | Standard Error 2.3845 |
| Salmeterol Xinafoate/Fluticasone Propionate | The Overall Change in Usage of Rescue Medication (Short Acting β2-agonist) . | 2.538 % of days | Standard Error 2.398 |
Secondary
The Percentage of Patients Who Permanently Discontinued Due to COPD Exacerbation
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.
Time frame: 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QMF149 | The Percentage of Patients Who Permanently Discontinued Due to COPD Exacerbation | 0.6 Percentage participants |
| Salmeterol Xinafoate/Fluticasone Propionate | The Percentage of Patients Who Permanently Discontinued Due to COPD Exacerbation | 1.6 Percentage participants |
Secondary
The Usage of Rescue Medication (Short Acting β2-agonist)
Participants record the number of puffs of rescue medication taken in the previous 12 hours each morning and evening throughout the 12 week treatment period.
Time frame: 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | The Usage of Rescue Medication (Short Acting β2-agonist) | Daily Change Weeks 1-12 (n-281,274) | -1.064 Number of puffs | Standard Error 0.1615 |
| QMF149 | The Usage of Rescue Medication (Short Acting β2-agonist) | Daytime Change Weeks 1-12 (n=276-272) | -0.625 Number of puffs | Standard Error 0.1021 |
| QMF149 | The Usage of Rescue Medication (Short Acting β2-agonist) | Nighttime Change Weeks 1-12 (n=281,271) | -0.452 Number of puffs | Standard Error 0.0748 |
| Salmeterol Xinafoate/Fluticasone Propionate | The Usage of Rescue Medication (Short Acting β2-agonist) | Daily Change Weeks 1-12 (n-281,274) | -0.593 Number of puffs | Standard Error 0.1621 |
| Salmeterol Xinafoate/Fluticasone Propionate | The Usage of Rescue Medication (Short Acting β2-agonist) | Daytime Change Weeks 1-12 (n=276-272) | -0.300 Number of puffs | Standard Error 0.1026 |
| Salmeterol Xinafoate/Fluticasone Propionate | The Usage of Rescue Medication (Short Acting β2-agonist) | Nighttime Change Weeks 1-12 (n=281,271) | -0.308 Number of puffs | Standard Error 0.0751 |
Secondary
Time (in Days) to Permanent Study Discontinuation Due to COPD Exacerbation
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.
Time frame: 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| QMF149 | Time (in Days) to Permanent Study Discontinuation Due to COPD Exacerbation | NA Days |
| Salmeterol Xinafoate/Fluticasone Propionate | Time (in Days) to Permanent Study Discontinuation Due to COPD Exacerbation | NA Days |
Secondary
Time to First COPD Exacerbation
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. The reported measure will detail the percentage of participants that were event free of a specified event.
Time frame: 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QMF149 | Time to First COPD Exacerbation | Moderate COPD exacerbation | 94.5 Percentage of participants event free |
| QMF149 | Time to First COPD Exacerbation | Moderate or Severe COPD exacerbation | 92.9 Percentage of participants event free |
| QMF149 | Time to First COPD Exacerbation | Severe COPD exacerbation | 98.0 Percentage of participants event free |
| QMF149 | Time to First COPD Exacerbation | Any( mild, moderate,severe) | 92.2 Percentage of participants event free |
| QMF149 | Time to First COPD Exacerbation | Mild COPD exacerbation | 99.3 Percentage of participants event free |
| Salmeterol Xinafoate/Fluticasone Propionate | Time to First COPD Exacerbation | Any( mild, moderate,severe) | 85.8 Percentage of participants event free |
| Salmeterol Xinafoate/Fluticasone Propionate | Time to First COPD Exacerbation | Mild COPD exacerbation | 98.7 Percentage of participants event free |
| Salmeterol Xinafoate/Fluticasone Propionate | Time to First COPD Exacerbation | Moderate COPD exacerbation | 88.5 Percentage of participants event free |
| Salmeterol Xinafoate/Fluticasone Propionate | Time to First COPD Exacerbation | Severe COPD exacerbation | 98.3 Percentage of participants event free |
| Salmeterol Xinafoate/Fluticasone Propionate | Time to First COPD Exacerbation | Moderate or Severe COPD exacerbation | 86.8 Percentage of participants event free |
Secondary
Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period
Total amount (in doses) of systemic corticosteroid used to treat COPD exacerbation will be summarized descriptively by treatment group per each systemic corticosteroid.
Time frame: 12 weeks
Population: Full analysis set consisting of all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV Hydrocortisone (mg) (n=0,1) | NA (Prednisolone dose equivalents) mg | — |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral Budesonide (mg) (n=0,1) | NA (Prednisolone dose equivalents) mg | — |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV methylprenisolone sodium succinate(mg)(n=1,0) | 250 (Prednisolone dose equivalents) mg | Standard Deviation 0 |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral methylprenisolone (mg) (n=7,13) | 16.57 (Prednisolone dose equivalents) mg | Standard Deviation 11.414 |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV dexamethasone (mg) (n=0,1) | NA (Prednisolone dose equivalents) mg | — |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral prednisolone (mg) (n=8,28) | 24.38 (Prednisolone dose equivalents) mg | Standard Deviation 9.52 |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV methylprenisolone sodium succinate(ug)(n=0,1) | NA (Prednisolone dose equivalents) mg | — |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral prednisone (mg) (n=8,16) | 31.25 (Prednisolone dose equivalents) mg | Standard Deviation 11.26 |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV Hydrocortisone sodium succinate (mg) (n=2,0) | 400.00 (Prednisolone dose equivalents) mg | Standard Deviation 282.843 |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral prednisone (ug) (n=0,1) | NA (Prednisolone dose equivalents) mg | — |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV prednisolone (mg) (n=0,1) | NA (Prednisolone dose equivalents) mg | — |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Inhalation budesonide (mL)(n=0,1) | NA (Prednisolone dose equivalents) mg | — |
| QMF149 | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IM Hydrocortisone (mg) (n=1,0) | 100 (Prednisolone dose equivalents) mg | Standard Deviation 0 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Inhalation budesonide (mL)(n=0,1) | 0.50 (Prednisolone dose equivalents) mg | Standard Deviation 0 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IM Hydrocortisone (mg) (n=1,0) | NA (Prednisolone dose equivalents) mg | — |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV dexamethasone (mg) (n=0,1) | 4.00 (Prednisolone dose equivalents) mg | Standard Deviation 0 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV Hydrocortisone (mg) (n=0,1) | 100 (Prednisolone dose equivalents) mg | Standard Deviation 0 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV Hydrocortisone sodium succinate (mg) (n=2,0) | NA (Prednisolone dose equivalents) mg | — |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV methylprenisolone sodium succinate(mg)(n=1,0) | NA (Prednisolone dose equivalents) mg | — |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV methylprenisolone sodium succinate(ug)(n=0,1) | 80 (Prednisolone dose equivalents) mg | Standard Deviation 0 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | IV prednisolone (mg) (n=0,1) | 250 (Prednisolone dose equivalents) mg | Standard Deviation 0 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral Budesonide (mg) (n=0,1) | 20 (Prednisolone dose equivalents) mg | Standard Deviation 0 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral methylprenisolone (mg) (n=7,13) | 20.31 (Prednisolone dose equivalents) mg | Standard Deviation 9.586 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral prednisolone (mg) (n=8,28) | 23.93 (Prednisolone dose equivalents) mg | Standard Deviation 13.06 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral prednisone (mg) (n=8,16) | 25.31 (Prednisolone dose equivalents) mg | Standard Deviation 11.176 |
| Salmeterol Xinafoate/Fluticasone Propionate | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period | Oral prednisone (ug) (n=0,1) | 10 (Prednisolone dose equivalents) mg | Standard Deviation 0 |
Secondary
Trough FEV1 After First Dose and After 4 Weeks of Treatment
Spirometry is conducted according to the global standard. FEV1 is measured at pre-dose and post dose up to 1 hours on Day 1 and Day 28; 24 hours post-dose on Day 29 and 85. In a subset of approximately 60 patients, FEV1 is measured up to 20 hours postdose on Day 28 and Day 84.
Time frame: Day 1 and Day 85
Population: All randomized patients were included in the Safety analysis set (SAF) and Full analysis set (FAS).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QMF149 | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Baseline Day 2 (n=286, 302) | 1.147 Liters | Standard Error 0.0237 |
| QMF149 | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Day 2 (n=286, 302) | 1.216 Liters | Standard Error 0.0106 |
| QMF149 | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Baseline Day 29 (n=293, 296) | 1.148 Liters | Standard Error 0.0236 |
| QMF149 | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Day 29 (n=293,296) | 1.277 Liters | Standard Error 0.0119 |
| QMF149 | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Day 84 baseline (n=289,287) | 1.144 Liters | Standard Error 0.024 |
| QMF149 | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Day 84 (n=289,287) | 1.269 Liters | Standard Error 0.0139 |
| Salmeterol Xinafoate/Fluticasone Propionate | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Day 84 baseline (n=289,287) | 1.187 Liters | Standard Error 0.0267 |
| Salmeterol Xinafoate/Fluticasone Propionate | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Baseline Day 2 (n=286, 302) | 1.167 Liters | Standard Error 0.0264 |
| Salmeterol Xinafoate/Fluticasone Propionate | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Day 29 (n=293,296) | 1.247 Liters | Standard Error 0.0119 |
| Salmeterol Xinafoate/Fluticasone Propionate | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Day 2 (n=286, 302) | 1.243 Liters | Standard Error 0.0104 |
| Salmeterol Xinafoate/Fluticasone Propionate | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Day 84 (n=289,287) | 1.208 Liters | Standard Error 0.0139 |
| Salmeterol Xinafoate/Fluticasone Propionate | Trough FEV1 After First Dose and After 4 Weeks of Treatment | Baseline Day 29 (n=293, 296) | 1.178 Liters | Standard Error 0.0266 |