Asthma
Conditions
Keywords
asthma, children, persistent
Brief summary
A study to compare the bronchodilatory effect of a single dose of Mometasone Furoate/Formoterol Fumarate (MF/F) pressurized metered dose inhaler (MDI) delivered with and without an AeroChamber Plus® with Flow-Vu® Anti-Static Valved Holding Chamber (spacer) versus Placebo MDI (combined with and without spacer) and formoterol fumarate (F) dry powder inhaler (DPI). Participants were randomly assigned to 1 of 6 treatment sequences and each participant was to receive a single dose of each of 4 treatments in each period. Each treatment period was separated by a 5 to 7 day washout period. It assumed that a single dose MF/F MDI 100/10 microgram (mcg) delivered with a spacer would produce bronchodilation, defined as a significant increase in forced expiratory volume in one second (FEV1) area under the curve from 0 to 12 hours (AUC\[0-12 hr\]) when compared to placebo.
Interventions
DRUGFormoterol Fumarate DPI
Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose
DRUGMometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
DRUGMometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
DRUGPlacebo MDI with spacer
Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
DRUGPlacebo MDI without spacer
Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
DRUGMometasone Furoate DPI
Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Must have a diagnosis of asthma of at least 6 months duration * Must have taken an Inhaled Corticosteroid (\[ICS\]; alone or in combination with a long-acting beta-2 Agonist \[LABA\]) for at least 3 months prior to the Screening Visit and must have been on a stable daily dose for at least 2 weeks prior to the Screening Visit * FEV1 must be at least 70% predicted after all restricted medications have been withheld for the appropriate intervals * Must demonstrate an increase in absolute FEV1 of at least 12% within 30 minutes after administration of 360 mcg albuterol (4 inhalations x 90 mcg, ex-actuator) or of nebulized albuterol (2.5 mg), if confirmed as standard office practice
Exclusion criteria
* Has been treated in the emergency room for a severe asthma exacerbation requiring systemic glucocorticosteroid treatment, or hospitalized for management of airway obstruction within 3 months prior to the Screening Visit * Has required ventilator support for respiratory failure secondary to asthma * Demonstrates a decrease in absolute FEV1 of \>20% at any time from the Screening Visit up to and including the Baseline Visit * Requires the use of greater than 8 inhalations per day of short-acting beta-2 agonists (SABA) MDI, or 2 or more nebulized treatments per day of 2.5 mg SABA on any 2 consecutive days from the Screening Visit up to and including the Baseline Visit * Experiences a clinical deterioration in asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids, but allowing SABA) as judged by the investigator, at any time from the Screening Visit up to and including the Baseline Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From 0-12 Hours (AUC[0-12h]) of the Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) After a Single Dose of MF/F MDI With Spacer Compared to Placebo MDI Combined With or Without Spacer | Up to 12 hours postdose | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer Compared to MF/F MDI Without Spacer | Up to 12 hours postdose | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. |
| Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose | Baseline was defined as the average of 2 predose measurements (taken 30 minutes and immediately before dosing). |
| AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F With Spacer Compared to F DPI | Up to 12 hours postdose | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. |
| AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose MF/F MDI Without Spacer Compared to Placebo MDI Combined With or Without Spacer | Up to 12 hours postdose | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. |
| AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of F DPI Compared to Placebo MDI Combined With or Without Spacer | Up to 12 hours postdose | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. |
| Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose | Baseline was defined as the average of 2 predose FVC measurements (taken 30 minutes and immediately before dosing). |
| AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F Without Spacer Compared to F DPI | Up to 12 hours postdose | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. |
Participant flow
Recruitment details
Participants were recruited from 28 study sites in the United States. Primary Therapy Period: December 2010 to October 2011.
Pre-assignment details
The study included a 4-week Run-In Period during which participants were treated with Mometasone Furoate (MF) Dry Powdered Inhaler (DPI) 100 mcg.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period 2 (1 Dose) | Protocol Violation | 1 | 1 | 0 | 0 | 0 | 1 |
| Treatment Period 2 (1 Dose) | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 3 (1 Dose) | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age, Customized 5-7 years | 17 participants |
| Age, Customized 8-11 years | 75 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 88 | 0 / 91 | 0 / 90 | 0 / 90 |
| serious Total, serious adverse events | 0 / 88 | 0 / 91 | 0 / 90 | 0 / 90 |
Outcome results
Primary
Area Under the Curve From 0-12 Hours (AUC[0-12h]) of the Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) After a Single Dose of MF/F MDI With Spacer Compared to Placebo MDI Combined With or Without Spacer
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule.
Time frame: Up to 12 hours postdose
Population: Participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, spacer and spirometry maneuvers; and used \>80% of prescribed MF DPI across the entire study treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MF/F MDI With Spacer | Area Under the Curve From 0-12 Hours (AUC[0-12h]) of the Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) After a Single Dose of MF/F MDI With Spacer Compared to Placebo MDI Combined With or Without Spacer | 0.115 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | Area Under the Curve From 0-12 Hours (AUC[0-12h]) of the Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) After a Single Dose of MF/F MDI With Spacer Compared to Placebo MDI Combined With or Without Spacer | -0.009 Liters | Standard Error 0.016 |
Comparison: Pairwise Treatment Comparison of MF/F MDI with spacer and Placebo MDI combined with or without spacer.~Analysis was performed using an analysis of covariance (ANCOVA) model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.p-value: <0.00195% CI: [0.094, 0.154]ANCOVA
Secondary
AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose MF/F MDI Without Spacer Compared to Placebo MDI Combined With or Without Spacer
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule.
Time frame: Up to 12 hours postdose
Population: Participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, spacer and spirometry maneuvers; and used \>80% of prescribed MF DPI across the entire study treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MF/F MDI With Spacer | AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose MF/F MDI Without Spacer Compared to Placebo MDI Combined With or Without Spacer | 0.093 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose MF/F MDI Without Spacer Compared to Placebo MDI Combined With or Without Spacer | -0.009 Liters | Standard Error 0.016 |
Comparison: Pairwise Treatment Comparison of MF/F MDI without spacer and Placebo MDI combined with or without spacer.~Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.p-value: <0.00195% CI: [0.073, 0.131]ANCOVA
Secondary
AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of F DPI Compared to Placebo MDI Combined With or Without Spacer
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule.
Time frame: Up to 12 hours postdose
Population: Participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, space and spirometry maneuvers; and used \>80% of prescribed MF DPI across the entire study treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MF/F MDI With Spacer | AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of F DPI Compared to Placebo MDI Combined With or Without Spacer | 0.097 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of F DPI Compared to Placebo MDI Combined With or Without Spacer | -0.009 Liters | Standard Error 0.016 |
Comparison: Pairwise Treatment Comparison of F DPI and Placebo MDI combined with or without spacer.~Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.p-value: <0.00195% CI: [0.077, 0.135]ANCOVA
Secondary
AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer Compared to MF/F MDI Without Spacer
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule.
Time frame: Up to 12 hours postdose
Population: Participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, spacer and spirometry maneuvers; and used \>80% of prescribed MF DPI across the entire study treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MF/F MDI With Spacer | AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer Compared to MF/F MDI Without Spacer | 0.115 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer Compared to MF/F MDI Without Spacer | 0.093 Liters | Standard Error 0.016 |
Comparison: Pairwise Treatment Comparison of MF/F MDI with spacer and MF/F MDI without spacer.~Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.p-value: 0.14495% CI: [-0.008, 0.052]ANCOVA
Secondary
AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F Without Spacer Compared to F DPI
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule.
Time frame: Up to 12 hours postdose
Population: Participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, space and spirometry maneuvers; and used \>80% of prescribed MF DPI across the entire study treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MF/F MDI With Spacer | AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F Without Spacer Compared to F DPI | 0.093 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F Without Spacer Compared to F DPI | 0.097 Liters | Standard Error 0.016 |
Comparison: Pairwise Treatment Comparison of MF/F MDI without spacer and F DPI.~Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.p-value: 0.7995% CI: [-0.033, 0.025]ANCOVA
Secondary
AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F With Spacer Compared to F DPI
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule.
Time frame: Up to 12 hours postdose
Population: Participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, space and spirometry maneuvers; and used \>80% of prescribed MF DPI across the entire study treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MF/F MDI With Spacer | AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F With Spacer Compared to F DPI | 0.115 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F With Spacer Compared to F DPI | 0.097 Liters | Standard Error 0.016 |
Comparison: Pairwise Treatment Comparison of MF/F MDI with spacer and F DPI.~Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.p-value: 0.22995% CI: [-0.012, 0.048]ANCOVA
Secondary
Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose
Baseline was defined as the average of 2 predose measurements (taken 30 minutes and immediately before dosing).
Time frame: Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose
Population: Participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, spacer and spirometry maneuvers; and used \>80% of prescribed MF DPI across the entire study treatment
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI With Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline (n=79, 79, 79, 79) | 1.554 Liters | Standard Error 0.049 |
| MF/F MDI With Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 5 minutes postdose (n=79, 79, 79, 79) | 0.111 Liters | Standard Error 0.014 |
| MF/F MDI With Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 30 minutes postdose (n=79, 79, 79, 79) | 0.131 Liters | Standard Error 0.017 |
| MF/F MDI With Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 1 hour postdose (n=79, 79, 79, 79) | 0.159 Liters | Standard Error 0.017 |
| MF/F MDI With Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 2 hours postdose (n=79, 79, 79, 79) | 0.136 Liters | Standard Error 0.018 |
| MF/F MDI With Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 4 hours postdose (n=79, 79, 79, 79) | 0.136 Liters | Standard Error 0.018 |
| MF/F MDI With Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 8 hours postdose (n=79, 79, 79, 79) | 0.108 Liters | Standard Error 0.018 |
| MF/F MDI With Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 12 hours postdose (n=78, 79, 78, 79) | 0.092 Liters | Standard Error 0.019 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 4 hours postdose (n=79, 79, 79, 79) | 0.115 Liters | Standard Error 0.018 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 2 hours postdose (n=79, 79, 79, 79) | 0.126 Liters | Standard Error 0.018 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 5 minutes postdose (n=79, 79, 79, 79) | 0.068 Liters | Standard Error 0.013 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 12 hours postdose (n=78, 79, 78, 79) | 0.046 Liters | Standard Error 0.018 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 8 hours postdose (n=79, 79, 79, 79) | 0.093 Liters | Standard Error 0.018 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 1 hour postdose (n=79, 79, 79, 79) | 0.131 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 30 minutes postdose (n=79, 79, 79, 79) | 0.099 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline (n=79, 79, 79, 79) | 1.563 Liters | Standard Error 0.049 |
| F DPI | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 8 hours postdose (n=79, 79, 79, 79) | 0.087 Liters | Standard Error 0.017 |
| F DPI | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 30 minutes postdose (n=79, 79, 79, 79) | 0.117 Liters | Standard Error 0.016 |
| F DPI | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 1 hour postdose (n=79, 79, 79, 79) | 0.136 Liters | Standard Error 0.016 |
| F DPI | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 2 hours postdose (n=79, 79, 79, 79) | 0.135 Liters | Standard Error 0.018 |
| F DPI | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 4 hours postdose (n=79, 79, 79, 79) | 0.118 Liters | Standard Error 0.018 |
| F DPI | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 12 hours postdose (n=78, 79, 78, 79) | 0.059 Liters | Standard Error 0.018 |
| F DPI | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline (n=79, 79, 79, 79) | 1.570 Liters | Standard Error 0.049 |
| F DPI | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 5 minutes postdose (n=79, 79, 79, 79) | 0.105 Liters | Standard Error 0.013 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 30 minutes postdose (n=79, 79, 79, 79) | 0.006 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 1 hour postdose (n=79, 79, 79, 79) | 0.007 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 5 minutes postdose (n=79, 79, 79, 79) | -0.001 Liters | Standard Error 0.014 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline (n=79, 79, 79, 79) | 1.547 Liters | Standard Error 0.049 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 2 hours postdose (n=79, 79, 79, 79) | 0.019 Liters | Standard Error 0.018 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 12 hours postdose (n=78, 79, 78, 79) | -0.033 Liters | Standard Error 0.019 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 8 hours postdose (n=79, 79, 79, 79) | -0.012 Liters | Standard Error 0.018 |
| Placebo MDI With or Without Spacer | Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 4 hours postdose (n=79, 79, 79, 79) | 0.005 Liters | Standard Error 0.018 |
Secondary
Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose
Baseline was defined as the average of 2 predose FVC measurements (taken 30 minutes and immediately before dosing).
Time frame: Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose
Population: Participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, space and spirometry maneuvers; and used \>80% of prescribed MF DPI across the entire study treatment
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI With Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline (n=79, 79, 79, 79) | 1.914 Liters | Standard Error 0.061 |
| MF/F MDI With Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 5 minutes postdose (n=79, 79, 79, 79) | 0.028 Liters | Standard Error 0.012 |
| MF/F MDI With Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 30 minutes postdose (n=79, 79, 79, 79) | 0.037 Liters | Standard Error 0.013 |
| MF/F MDI With Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 1 hour postdose (n=79, 79, 79, 79) | 0.048 Liters | Standard Error 0.015 |
| MF/F MDI With Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 2 hours postdose (n=79, 79, 79, 79) | 0.023 Liters | Standard Error 0.015 |
| MF/F MDI With Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 4 hours postdose (n=79, 79, 79, 79) | 0.031 Liters | Standard Error 0.015 |
| MF/F MDI With Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 8 hours postdose (n=79, 79, 79, 79) | -0.001 Liters | Standard Error 0.016 |
| MF/F MDI With Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 12 hours postdose (n=78, 79, 78, 79) | -0.001 Liters | Standard Error 0.017 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 4 hours postdose (n=79, 79, 79, 79) | 0.018 Liters | Standard Error 0.015 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 2 hours postdose (n=79, 79, 79, 79) | 0.026 Liters | Standard Error 0.015 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 5 minutes postdose (n=79, 79, 79, 79) | 0.005 Liters | Standard Error 0.012 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 12 hours postdose (n=78, 79, 78, 79) | -0.022 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 8 hours postdose (n=79, 79, 79, 79) | 0.007 Liters | Standard Error 0.015 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 1 hour postdose (n=79, 79, 79, 79) | 0.027 Liters | Standard Error 0.014 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 30 minutes postdose (n=79, 79, 79, 79) | 0.020 Liters | Standard Error 0.013 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline (n=79, 79, 79, 79) | 1.931 Liters | Standard Error 0.061 |
| F DPI | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 8 hours postdose (n=79, 79, 79, 79) | -0.013 Liters | Standard Error 0.015 |
| F DPI | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 30 minutes postdose (n=79, 79, 79, 79) | 0.017 Liters | Standard Error 0.013 |
| F DPI | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 1 hour postdose (n=79, 79, 79, 79) | 0.022 Liters | Standard Error 0.014 |
| F DPI | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 2 hours postdose (n=79, 79, 79, 79) | 0.047 Liters | Standard Error 0.015 |
| F DPI | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 4 hours postdose (n=79, 79, 79, 79) | 0.008 Liters | Standard Error 0.015 |
| F DPI | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 12 hours postdose (n=78, 79, 78, 79) | -0.014 Liters | Standard Error 0.016 |
| F DPI | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline (n=79, 79, 79, 79) | 1.928 Liters | Standard Error 0.061 |
| F DPI | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 5 minutes postdose (n=79, 79, 79, 79) | 0.032 Liters | Standard Error 0.012 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 30 minutes postdose (n=79, 79, 79, 79) | 0.009 Liters | Standard Error 0.013 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 1 hour postdose (n=79, 79, 79, 79) | -0.003 Liters | Standard Error 0.014 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 5 minutes postdose (n=79, 79, 79, 79) | 0.018 Liters | Standard Error 0.012 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline (n=79, 79, 79, 79) | 1.913 Liters | Standard Error 0.061 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 2 hours postdose (n=79, 79, 79, 79) | 0.015 Liters | Standard Error 0.015 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 12 hours postdose (n=78, 79, 78, 79) | -0.012 Liters | Standard Error 0.016 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 8 hours postdose (n=79, 79, 79, 79) | -0.006 Liters | Standard Error 0.015 |
| Placebo MDI With or Without Spacer | Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | 4 hours postdose (n=79, 79, 79, 79) | -0.006 Liters | Standard Error 0.015 |