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The primary objective of this study is to evaluate the dose response, efficacy, and safety of 4 different doses of salmeterol Spiromax (6.25, 12.5, 25, and 50 mcg) each combined with a fixed dose of fluticasone propionate (100 mcg) delivered as Fluticasone/Salmeterol Spiromax® Inhalation Powder (FS Spiromax) when administered as a single dose in subjects 12 years of age and older with persistent asthma.
This was a multicenter, randomized, double-blind and open-label active-controlled, single-dose, 6 period crossover, dose-ranging study conducted in male and female subjects ages 12 years and older with persistent asthma.
Fluticasone propionate multidose dry powder inhaler (Fp MDPI) 50 mcg was provided (to replace the subject's current inhaled corticosteroid (ICS)) throughout the 14 day run-in period and each of the washout periods between treatments. Subjects were instructed to administer 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily during the run-in and washout periods. All other medications for the treatment of asthma were discontinued at or prior to the screening visit.
A short-acting β2-adrenergic agonist (SABA), salbuterol HFA, MDI, was provided (to replace the subject's current rescue medication) for symptomatic relief of asthma symptoms in each the run-in, treatment, and washout periods.
Treatment period lasted 5 weeks with a 5 to 7 day washout between each of the six single dose treatments:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FS MDPI 100/6.25 mcg | Experimental | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate. |
|
| FS MDPI 100/12.5mcg | Experimental | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate. |
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| FS MDPI 100/25 | Experimental | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate. |
|
| FS MDPI 100/50 | Experimental | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. |
|
| Fp MDPI 100 mcg | Active Comparator | Subjects inhaled a single dose of 100 mcg fluticasone propionate. |
|
| Advair Diskus 100/50 mcg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fp MDPI | Drug | Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened. Fp at 100 mcg was an active comparator (single dose). Further, participants were instructed to administer two inhalations of Fp MDPI 50 mcg twice daily (100 mcg total dose) during the Run-in (to replace the participant's current inhaled corticosteroid) and Washout Periods between treatments. |
| Measure | Description | Time Frame |
|---|---|---|
| Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) | Standardized baseline-adjusted FEV1 AUC0-12 was defined as the area under the curve for baseline-adjusted FEV1 measurements from the predose to 12 hours postdose time points using the trapezoidal rule based on actual (not scheduled) time of measurement and was standardized by dividing the actual time of last non-missing FEV1 measurement. Baseline-adjusted FEV1 was calculated as postdose FEV1 after subtracting period-specific baseline FEV1. The period-specific baseline FEV1 was measured at predose within 5 minutes of AM dose administration at each treatment visit. If that value was missing, then FEV1 measured at 30 minutes predose was used as the period-specific baseline. | Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment | The secondary efficacy variable was the change from period-specific baseline in FEV1 at 12 hours, calculated as FEV1 measured at 12 hours postdose after subtracting period-specific baseline FEV1 at each treatment period. The period-specific baseline FEV1 was measured at predose within 5 minutes of AM dose administration at each treatment visit. If that value was missing, then FEV1 measured at 30 minutes predose was used as the period-specific baseline. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Teva Investigational Site 10453 | Denver | Colorado | United States | |||
| Teva Investigational Site 10452 |
Ten subjects failed randomization.
A total of 105 subjects with asthma were screened for this study. Of the 105 subjects screened, 82 subjects at 10 investigational sites in the US met entry criteria and were considered to be eligible to enter the run-in period.
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | All subjects, regardless of the order of treatments to which they were randomized in this cross-over study. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Active Comparator |
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms. |
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| FS MDPI | Drug | FS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate and salmeterol xinafoate dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened. The fluticasone propionate component was a fixed dose of 100 mcg. The salmeterol xinofoate dosage varied: 6.25, 12.5, 25 or 50 mcg. |
|
|
| Advair Diskus | Drug | ADVAIR DISKUS (100/50 mcg fluticasone propionate/salmeterol xinafoate) consists of a dry powder formulation of fluticasone propionate and salmeterol xinafoate in a lactose excipient. The dry powder is contained within individual blisters on a double foil strip within the device. Activation of the device opens a single blister of medication which is then dispersed into the air-stream by patient inhalation. |
|
|
| Albuterol | Drug | Albuterol (Pro-Air) hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication). |
|
|
| Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 12 hours |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol | Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. The primary pharmacokinetic parameters were AUC0-t and Cmax for Salmeterol. | Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose |
| Maximum Observed Plasma Concentration (Cmax) of Salmeterol | Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. The primary pharmacokinetic parameters were AUC0-t and Cmax for Salmeterol. | Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose |
| Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol | Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. | Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose |
| Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | TEAEs were recorded during each double-blind treatment. In addition, at the end of each treatment, patients continued to use 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily, so adverse events during this treatment were assigned to Fp MDPI 50 mcg. An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical in | Day 1 up to Day 35 |
| North Dartmouth |
| Massachusetts |
| United States |
| Teva Investigational Site 10455 | St Louis | Missouri | United States |
| Teva Investigational Site 10454 | Skillman | New Jersey | United States |
| Teva Investigational Site 10448 | Raleigh | North Carolina | United States |
| Teva Investigational Site 10451 | Medford | Oregon | United States |
| Teva Investigational Site 10449 | Portland | Oregon | United States |
| Teva Investigational Site 10457 | El Paso | Texas | United States |
| Teva Investigational Site 10450 | New Braunfels | Texas | United States |
| Teva Investigational Site 10456 | San Antonio | Texas | United States |
| Received Fp MDPI 100 mcg |
|
| Received FS MDPI 100/6.25 mcg |
|
| Received FS MDPI 100/12.5mcg |
|
| Received FS MDPI 100/25 mcg |
|
| Received FS MDPI 100/50 mcg |
|
| Received Advair Diskus 100/50 mcg |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
Intent-to-Treat population
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All subjects, regardless of the order of treatments to which they were randomized in this cross-over study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| |||||||||||||||||||||||
| Weight | Mean | Standard Deviation | kg |
| ||||||||||||||||||||||
| Height | Mean | Standard Deviation | cm |
| ||||||||||||||||||||||
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) | Standardized baseline-adjusted FEV1 AUC0-12 was defined as the area under the curve for baseline-adjusted FEV1 measurements from the predose to 12 hours postdose time points using the trapezoidal rule based on actual (not scheduled) time of measurement and was standardized by dividing the actual time of last non-missing FEV1 measurement. Baseline-adjusted FEV1 was calculated as postdose FEV1 after subtracting period-specific baseline FEV1. The period-specific baseline FEV1 was measured at predose within 5 minutes of AM dose administration at each treatment visit. If that value was missing, then FEV1 measured at 30 minutes predose was used as the period-specific baseline. | The full analysis set (FAS) included all subjects in the ITT population who received at least 1 dose of study drug and had at least 1 evaluable standardized baseline-adjusted FEV1 AUC0-12. | Posted | Least Squares Mean | Standard Error | mL | Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours |
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment | The secondary efficacy variable was the change from period-specific baseline in FEV1 at 12 hours, calculated as FEV1 measured at 12 hours postdose after subtracting period-specific baseline FEV1 at each treatment period. The period-specific baseline FEV1 was measured at predose within 5 minutes of AM dose administration at each treatment visit. If that value was missing, then FEV1 measured at 30 minutes predose was used as the period-specific baseline. | The full analysis set (FAS) included all subjects in the ITT population who received at least 1 dose of study drug and had at least 1 evaluable standardized baseline-adjusted FEV1 AUC0-12. | Posted | Least Squares Mean | Standard Error | mL | Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 12 hours |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol | Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. The primary pharmacokinetic parameters were AUC0-t and Cmax for Salmeterol. | Pharmacokinetic Analysis set. PK parameters for Salmeterol were not run for Fp MDPI experience. | Posted | Mean | Standard Deviation | pg*hr/mL | Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Observed Plasma Concentration (Cmax) of Salmeterol | Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. The primary pharmacokinetic parameters were AUC0-t and Cmax for Salmeterol. | Pharmacokinetic Analysis set. PK parameters for Salmeterol were not run for Fp MDPI experience. | Posted | Mean | Standard Deviation | pg/mL | Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol | Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. | Pharmacokinetic Analysis set. PK parameters for Salmeterol were not run for Fp MDPI experience. | Posted | Median | Full Range | hours | Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose |
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| Secondary | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | TEAEs were recorded during each double-blind treatment. In addition, at the end of each treatment, patients continued to use 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily, so adverse events during this treatment were assigned to Fp MDPI 50 mcg. An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical in | Safety population | Posted | Count of Participants | Participants | Day 1 up to Day 35 |
|
Day 1 to Day 35
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Fp MDPI 100 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate. | 0 | 67 | 0 | 67 | 0 | 67 |
| EG001 | FS MDPI 100/6.25 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate. | 0 | 68 | 0 | 68 | 0 | 68 |
| EG002 | FS MDPI 100/12.5mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate. | 0 | 69 | 0 | 69 | 0 | 69 |
| EG003 | FS MDPI 100/25 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate. | 0 | 67 | 0 | 67 | 0 | 67 |
| EG004 | FS MDPI 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. | 0 | 68 | 0 | 68 | 0 | 68 |
| EG005 | Advair Diskus 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms. | 0 | 66 | 0 | 66 | 0 | 66 |
| EG006 | Fp MDPI 50 mcg X 2 BID | Patients used 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily during the 'washout' between treatment periods, so adverse events during this treatment were assigned to Fp MDPI 50 mcg. | 0 | 72 | 0 | 72 | 4 | 72 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
|
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research | Teva Branded Pharmaceutical Products, R&D Inc. | 1-215-591-3000 |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000068298 | Fluticasone |
| D000068299 | Salmeterol Xinafoate |
| D000068297 | Fluticasone-Salmeterol Drug Combination |
| D000420 | Albuterol |
| D017265 | Procaterol |
| ID | Term |
|---|---|
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D006912 | Hydroxyquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
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| Other |
|
| Other |
linearity statistical test |
| The estimated treatment difference from the ANCOVA model between FS MDPI 100/50 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | <0.0001 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | 251.30 | 2-Sided | 95 | 215.6 | 287.1 | FS MDPI 100/50 mcg - Fp MDPI 100 mcg | Superiority |
| The estimated treatment difference from the ANCOVA model between FS MDPI 100/25 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | <0.0001 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | 227.56 | 2-Sided | 95 | 191.6 | 263.5 | FS MDPI 100/25 mcg - Fp MDPI 100 mcg | Superiority |
| The estimated treatment difference from the ANCOVA model between FS MDPI 100/512.5 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | <0.0001 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | 196.85 | 2-Sided | 95 | 161.2 | 232.5 | FS MDPI 100/12.5 mcg - Fp MDPI 100 mcg | Superiority |
| The estimated treatment difference from the ANCOVA model between FS MDPI 100/6.25 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | <0.0001 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | 151.71 | 2-Sided | 95 | 115.9 | 187.5 | FS MDPI 100/6.25 mcg - Fp MDPI 100 mcg | Superiority |
| The estimated treatment difference from the ANCOVA model between Advair Diskus 100/50 mcg dose group and Fp MDPI 100 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | <0.0001 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | 193.42 | 2-Sided | 95 | 157.4 | 229.5 | Advair Diskus 100/50 mcg - Fp MDPI 100 | Superiority |
| The estimated treatment difference from the ANCOVA model between FS MDPI 100/50 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | 0.0017 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | 57.88 | 2-Sided | 95 | 22.0 | 93.7 | FS MDPI 100/50 - Advair Diskus 100/50 mcg | Superiority |
| The estimated treatment difference from the ANCOVA model between FS MDPI 100/25 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | 0.0624 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | 34.14 | 2-Sided | 95 | -1.8 | 70.1 | FS MDPI 100/25 mcg - Advair Diskus 100/50 mcg | Superiority |
| The estimated treatment difference from the ANCOVA model between FS MDPI 100/12.5 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | 0.8503 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | 3.42 | 2-Sided | 95 | -32.3 | 39.1 | FS MDPI 100/12.5mcg - Advair Diskus 100/50 mcg | Superiority |
| The estimated treatment difference from the ANCOVA model between FS MDPI 100/6.25 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | 0.0229 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | -41.72 | 2-Sided | 95 | -77.6 | -5.8 | FS MDPI 100/6.25 mcg - Advair Diskus 100/50 mcg | Superiority |
| The estimated treatment difference from the ANCOVA model between Fp MDPI 100 mcg dose group and Advair Diskus 100/50 mcg group is presented together with the two-sided 95% CI for the difference and the p-value. | ANCOVA | Fixed effects of sequence, period and treatment; a random effect of subject within sequence; and a covariate of period-specific baseline FEV1. | <0.0001 | A fixed-sequence testing procedure was employed to control the overall Type I error rate at the 2 sided 0.05 level. | LSM difference | -193.42 | 2-Sided | 95 | -229.5 | -157.4 | Fp MDPI 100 mcg - Advair Diskus 100/50 mcg | Superiority |
| OG003 | FS MDPI 100/25 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate. |
| OG004 | FS MDPI 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. |
| OG005 | Advair Diskus 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms. |
|
|
|
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate. |
| OG004 | FS MDPI 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. |
| OG005 | Advair Diskus 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms. |
|
|
|
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
| OG004 | FS MDPI 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. |
| OG005 | Advair Diskus 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms. |
|
|
|
| OG004 | FS MDPI 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. |
| OG005 | Advair Diskus 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms. |
|
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| OG002 | FS MDPI 100/12.5mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate. |
| OG003 | FS MDPI 100/25 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate. |
| OG004 | FS MDPI 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. |
| OG005 | Advair Diskus 100/50 mcg | Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms. |
| OG006 | Fp MDPI 50 mcg X 2 BID | Patients used 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily during the 'washout' between treatment periods, so adverse events during this treatment were assigned to Fp MDPI 50 mcg. |
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