Asthma
Conditions
Keywords
Asthma, dry powder inhaler, long-acting beta2-agonist, bronchodilation, bronchodilator, metered dose inhaler, inhaled corticosteroid
Brief summary
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.
Detailed description
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: * fluticasone propionate/salmeterol xinafoate multidose dry powder inhaler (FS MDPI) given in doses of 6.25, 12.5, 25, or 50 mcg of salmeterol xinafoate in blinded fashion. * fluticasone propionate multidose dry powder inhaler (Fp MDPI) 100 mcg in blinded fashion * ADVAIR DISKUS, 100/50 mcg in open-label fashion
Interventions
DRUGFp MDPI
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.
DRUGFS MDPI
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.
DRUGAdvair Diskus
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.
DRUGAlbuterol
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).
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent/assent * General good health * Diagnosis of asthma as defined by the National Institutes of Health (NIH) * A best FEV1 of 40%-85% of the predicted normal value during the screening visit (SV) * Subjects need to demonstrate a ≥ 15% reversibility of FEV1 within 30 minutes following 4 inhalations of albuterol inhalation aerosol (if required, spacers are permitted for reversibility testing) at the SV. * Other inclusion criteria apply
Exclusion criteria
* History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation. * Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that is not resolved within 2 weeks prior to the SV. * Any asthma exacerbation requiring oral corticosteroids within 3 months of the SV. A subject must not have had any hospitalization for asthma within 6 months prior to the SV. * Taking long-acting β-agonists within 2 weeks of the SV * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) | Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment | Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 12 hours | 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol | Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose | 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. |
| Maximum Observed Plasma Concentration (Cmax) of Salmeterol | Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose | 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. |
| Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol | Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose | 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. |
| Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Day 1 up to Day 35 | 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 |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
Ten subjects failed randomization.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All subjects, regardless of the order of treatments to which they were randomized in this cross-over study. | 72 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Other | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 42.5 years STANDARD_DEVIATION 13.87 |
| Body Mass Index | 27.3 kg/m^2 STANDARD_DEVIATION 3.35 |
| Height | 170.0 cm STANDARD_DEVIATION 9.76 |
| Race/Ethnicity, Customized Black | 7 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 64 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 35 Participants |
| Weight | 79.2 kg STANDARD_DEVIATION 14.17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 68 | 0 / 69 | 0 / 67 | 0 / 68 | 0 / 66 | 0 / 72 |
| other Total, other adverse events | 0 / 67 | 0 / 68 | 0 / 69 | 0 / 67 | 0 / 68 | 0 / 66 | 4 / 72 |
| serious Total, serious adverse events | 0 / 67 | 0 / 68 | 0 / 69 | 0 / 67 | 0 / 68 | 0 / 66 | 0 / 72 |
Outcome results
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.
Time frame: Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fp MDPI 100 mcg | Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) | 52.13 mL | Standard Error 38.071 |
| FS MDPI 100/6.25 mcg | Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) | 203.84 mL | Standard Error 38.072 |
| FS MDPI 100/12.5mcg | Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) | 248.98 mL | Standard Error 38.025 |
| FS MDPI 100/25 mcg | Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) | 279.69 mL | Standard Error 38.121 |
| FS MDPI 100/50 mcg | Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) | 303.43 mL | Standard Error 38.062 |
| Advair Diskus 100/50 mcg | Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) | 245.56 mL | Standard Error 38.148 |
Comparison: A linear in log-dose-trend contrast was constructed to evaluate the dose-response trend, where the logarithm of dose was defined precisely as log (dose+1) to accommodate the case of Fp MDPI 100 mcg, since the dose used in this trend analysis was the salmeterol dose. The study was considered positive if the trend test was positive and the test involving the highest FS MDPI dose (100/50 mcg) compared with Fp MDPI 100 mcg was positive, regardless of the results of the tests for the other doses.p-value: <0.0001ANCOVA
Comparison: 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.p-value: <0.000195% CI: [215.6, 287.1]ANCOVA
Comparison: 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.p-value: <0.000195% CI: [191.6, 263.5]ANCOVA
Comparison: 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.p-value: <0.000195% CI: [161.2, 232.5]ANCOVA
Comparison: 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.p-value: <0.000195% CI: [115.9, 187.5]ANCOVA
Comparison: 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.p-value: <0.000195% CI: [157.4, 229.5]ANCOVA
Comparison: 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.p-value: 0.001795% CI: [22, 93.7]ANCOVA
Comparison: 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.p-value: 0.062495% CI: [-1.8, 70.1]ANCOVA
Comparison: 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.p-value: 0.850395% CI: [-32.3, 39.1]ANCOVA
Comparison: 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.p-value: 0.022995% CI: [-77.6, -5.8]ANCOVA
Comparison: 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.p-value: <0.000195% CI: [-229.5, -157.4]ANCOVA
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.
Time frame: Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose
Population: Pharmacokinetic Analysis set. PK parameters for Salmeterol were not run for Fp MDPI experience.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FS MDPI 100/6.25 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol | 32.8 pg*hr/mL | Standard Deviation 20.98 |
| FS MDPI 100/12.5mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol | 69.9 pg*hr/mL | Standard Deviation 35.36 |
| FS MDPI 100/25 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol | 133.5 pg*hr/mL | Standard Deviation 63.13 |
| FS MDPI 100/50 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol | 309.3 pg*hr/mL | Standard Deviation 143.43 |
| Advair Diskus 100/50 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol | 173.5 pg*hr/mL | Standard Deviation 106.59 |
Comparison: The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=5890% CI: [1.69, 2.202]
Comparison: The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=5990% CI: [0.702, 0.911]
Comparison: The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=6190% CI: [0.376, 0.485]
Comparison: The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=5990% CI: [0.151, 0.196]
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.
Time frame: Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 12 hours
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fp MDPI 100 mcg | Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment | 11.53 mL | Standard Error 29.058 |
| FS MDPI 100/6.25 mcg | Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment | 128.49 mL | Standard Error 29.109 |
| FS MDPI 100/12.5mcg | Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment | 170.51 mL | Standard Error 28.99 |
| FS MDPI 100/25 mcg | Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment | 209.85 mL | Standard Error 29.127 |
| FS MDPI 100/50 mcg | Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment | 238.30 mL | Standard Error 28.988 |
| Advair Diskus 100/50 mcg | Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment | 170.54 mL | Standard Error 29.23 |
Comparison: The estimated treatment difference from the ANCOVA model between each 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.p-value: <0.000195% CI: [62.4, 171.6]ANCOVA
Comparison: The estimated treatment difference from the ANCOVA model between each 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.p-value: <0.000195% CI: [104.3, 213.7]ANCOVA
Comparison: The estimated treatment difference from the ANCOVA model between each 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.p-value: 0.01595% CI: [13.3, 122.2]ANCOVA
Comparison: The estimated treatment difference from the ANCOVA model between each 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.p-value: <0.000195% CI: [172.4, 281.1]ANCOVA
Comparison: The estimated treatment difference from the ANCOVA model between each 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.p-value: <0.000195% CI: [143.7, 252.9]ANCOVA
Comparison: The estimated treatment difference from the ANCOVA model between each FS MDPI 100/12.5 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.p-value: <0.000195% CI: [104.7, 213.3]ANCOVA
Comparison: The estimated treatment difference from the ANCOVA model between each 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.p-value: 0.157895% CI: [-15.3, 94]ANCOVA
Comparison: The estimated treatment difference from the ANCOVA model between each 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.p-value: 0.999395% CI: [-54.4, 54.4]ANCOVA
Comparison: The estimated treatment difference from the ANCOVA model between each 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.p-value: 0.131195% CI: [-96.7, 12.6]ANCOVA
Comparison: The estimated treatment difference from the ANCOVA model between each 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.p-value: <0.000195% CI: [-213.7, -104.3]ANCOVA
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.
Time frame: Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose
Population: Pharmacokinetic Analysis set. PK parameters for Salmeterol were not run for Fp MDPI experience.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FS MDPI 100/6.25 mcg | Maximum Observed Plasma Concentration (Cmax) of Salmeterol | 16.0 pg/mL | Standard Deviation 8.86 |
| FS MDPI 100/12.5mcg | Maximum Observed Plasma Concentration (Cmax) of Salmeterol | 35.8 pg/mL | Standard Deviation 20.25 |
| FS MDPI 100/25 mcg | Maximum Observed Plasma Concentration (Cmax) of Salmeterol | 67.5 pg/mL | Standard Deviation 34.71 |
| FS MDPI 100/50 mcg | Maximum Observed Plasma Concentration (Cmax) of Salmeterol | 154.5 pg/mL | Standard Deviation 80.28 |
| Advair Diskus 100/50 mcg | Maximum Observed Plasma Concentration (Cmax) of Salmeterol | 42.3 pg/mL | Standard Deviation 19.28 |
Comparison: The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=5890% CI: [3.149, 4.168]
Comparison: The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=5990% CI: [1.335, 1.763]
Comparison: The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=6190% CI: [0.694, 0.911]
Comparison: The analysis is based on ANOVA model of the log transformed data, with fixed effects of sequence, period and treatment, and a random effect for subject within sequence. n=5990% CI: [0.295, 0.39]
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
Time frame: Day 1 up to Day 35
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fp MDPI 100 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Withdrawn from treatment due to AE | 0 Participants |
| Fp MDPI 100 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Severe adverse event | 0 Participants |
| Fp MDPI 100 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Deaths | 0 Participants |
| Fp MDPI 100 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Any adverse event | 2 Participants |
| Fp MDPI 100 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Treatment-related adverse event | 0 Participants |
| Fp MDPI 100 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Other serious adverse events | 0 Participants |
| FS MDPI 100/6.25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Any adverse event | 2 Participants |
| FS MDPI 100/6.25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Deaths | 0 Participants |
| FS MDPI 100/6.25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Withdrawn from treatment due to AE | 0 Participants |
| FS MDPI 100/6.25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Severe adverse event | 0 Participants |
| FS MDPI 100/6.25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Other serious adverse events | 0 Participants |
| FS MDPI 100/6.25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Treatment-related adverse event | 0 Participants |
| FS MDPI 100/12.5mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Other serious adverse events | 0 Participants |
| FS MDPI 100/12.5mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Treatment-related adverse event | 1 Participants |
| FS MDPI 100/12.5mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Withdrawn from treatment due to AE | 0 Participants |
| FS MDPI 100/12.5mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Deaths | 0 Participants |
| FS MDPI 100/12.5mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Any adverse event | 3 Participants |
| FS MDPI 100/12.5mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Severe adverse event | 0 Participants |
| FS MDPI 100/25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Other serious adverse events | 0 Participants |
| FS MDPI 100/25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Any adverse event | 1 Participants |
| FS MDPI 100/25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Severe adverse event | 0 Participants |
| FS MDPI 100/25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Treatment-related adverse event | 0 Participants |
| FS MDPI 100/25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Deaths | 0 Participants |
| FS MDPI 100/25 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Withdrawn from treatment due to AE | 0 Participants |
| FS MDPI 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Deaths | 0 Participants |
| FS MDPI 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Severe adverse event | 1 Participants |
| FS MDPI 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Other serious adverse events | 0 Participants |
| FS MDPI 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Withdrawn from treatment due to AE | 0 Participants |
| FS MDPI 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Treatment-related adverse event | 0 Participants |
| FS MDPI 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Any adverse event | 1 Participants |
| Advair Diskus 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Treatment-related adverse event | 1 Participants |
| Advair Diskus 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Deaths | 0 Participants |
| Advair Diskus 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Severe adverse event | 0 Participants |
| Advair Diskus 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Other serious adverse events | 0 Participants |
| Advair Diskus 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Any adverse event | 3 Participants |
| Advair Diskus 100/50 mcg | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Withdrawn from treatment due to AE | 0 Participants |
| Fp MDPI 50 mcg X 2 BID | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Treatment-related adverse event | 1 Participants |
| Fp MDPI 50 mcg X 2 BID | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Severe adverse event | 1 Participants |
| Fp MDPI 50 mcg X 2 BID | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Withdrawn from treatment due to AE | 1 Participants |
| Fp MDPI 50 mcg X 2 BID | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Deaths | 0 Participants |
| Fp MDPI 50 mcg X 2 BID | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Other serious adverse events | 0 Participants |
| Fp MDPI 50 mcg X 2 BID | Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period | Any adverse event | 17 Participants |
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.
Time frame: Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose
Population: Pharmacokinetic Analysis set. PK parameters for Salmeterol were not run for Fp MDPI experience.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FS MDPI 100/6.25 mcg | Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol | 0.1 hours |
| FS MDPI 100/12.5mcg | Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol | 0.1 hours |
| FS MDPI 100/25 mcg | Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol | 0.1 hours |
| FS MDPI 100/50 mcg | Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol | 0.1 hours |
| Advair Diskus 100/50 mcg | Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol | 0.5 hours |