Asthma
Conditions
Brief summary
This study compares the 12-week efficacy and 24-week safety of mometasone furoate/formoterol fumarate (MF/F) 100/10 mcg and mometasone furate (MF) 100 mcg, both administered twice daily (BID) via metered-dose inhaler (MDI) in children aged 5 to 11 years with persistent asthma.
Interventions
DRUGMF MDI 100 mcg BID (Open Label)
Eligible participants will receive open-label MF MDI 100 mcg BID during a 2-week run-in period.
DRUGMF/F MDI 100/10 mcg BID
After a 2 week run-in on open-label MF MDI 100 mcg BID, eligible participants will receive double-blinded treatment with MF/F MDI 100/10 mcg BID.
DRUGMF MDI 100 mcg BID
After a 2 week run-in on open-label MF MDI 100 mcg BID, eligible participants will receive double-blinded treatment with MF MDI 100 mcg BID.
DRUGAlbuterol/Salbutamol PRN
Participants may use study-provided short-acting beta agonist (SABA), albuterol/salbutamol, as needed (PRN) for the relief of asthma symptoms.
Participants may use a systemic corticosteroid (prednisone/prednisolone) for acute asthma worsening per investigator discretion.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
1:1 randomization to double-blinded MF/F MDI 100/10 mcg BID and MF MDI 100 mcg BID
Eligibility
Sex/Gender
ALL
Age
5 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Has a diagnosis of asthma of ≥ 6-months duration according to the Global Initiative for Asthma (GINA) guidelines * Has asthma that is adequately controlled on a stable dose of inhaled corticosteroid (ICS) combined with long-acting beta-agonist (LABA) ≥ 4 weeks * Is able to demonstrate an FEV1 \>60% and ≤90% predicted * Is able to demonstrate an increase in absolute FEV1 of at least 12% within 30 minutes after administration of albuterol/salbutamol. * Is able to use an MDI (without spacer), use a peak flow meter, and perform spirometry correctly. * Is willing (with consent of their parent(s)/guardian) to discontinue previously prescribed asthma medication, if there is no inherent harm in changing the participant's current asthma therapy. * Has laboratory tests that are clinically acceptable to the investigator.
Exclusion criteria
* Requires \>8 inhalations per day of albuterol (100 mcg per actuation), and/or \>2 nebulized treatments per day of 2.5 mg albuterol on any 2 consecutive days * Has a clinical worsening of asthma that results in emergency room visit (for an asthma exacerbation), hospitalization due to asthma, or treatment with additional, excluded asthma medication (other than SABA) between the Screening and Baseline visits. * Is considered by the investigator to have unstable asthma at the end of the run-in period * Has had \> 4 asthma exacerbations (defined as a worsening of asthma requiring systemic corticosteroid use and/or ≥ 24-hour stay in an emergency department, urgent care center, or hospital) within 1 year prior to visit 1 * Has had a history of life-threatening asthma * Has a clinically significant condition or situation, other than the condition being studied which may interfere with trial evaluations, participant safety, or optimal participation in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Morning (AM) Post-Dose % Predicted Forced Expiratory Volume in One Second (FEV1) in the Area Under the Curve (AUC)0-60 | Baseline, and average of Day 1, Weeks 1, 4, 8, and 12 | This endpoint reflects changes in lung function data (forced expiratory volume in 1 second) measured across 0 to 60 minutes post-dose (at 0, 5, 15, 30 and 60 minutes) and averaged across study visits in the Treatment Period (Day 1, Week 1, Week 4, Week 8 and Week 12) compared to Baseline. Baseline was the average of % predicted FEV1 values at 30 min and 0 min pre-dose. At each visit, the area under the curve is calculated over the post-dose timepoints. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC. |
| Count (Percentage) of Participants Experiencing At Least One Adverse Event (AE) | Up to 26 weeks | An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition temporally associated with the use of the Sponsor's product, is also an AE. |
| Count (Percentage) of Participants Discontinuing From Study Medication Due to An AE | Up to 24 weeks | An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition temporally associated with the use of the Sponsor's product, is also an AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Total Daily Use of Short-Acting Beta-Agonist (SABA) Rescue Medication With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Baseline and Weeks 1-12 (Averaged) | To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the change from baseline in total daily short-acting beta-agonist (SABA) use (puffs per day) was averaged and assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for as-needed relief of asthma symptoms. This secondary analysis of the change from baseline used the cLDA method without multiple imputation.A model-based MAR approach was used for missing data. |
| Participants Using SABA Rescue Medication Across Weeks 1-12 of the Treatment Period | Baseline and Weeks 1-12 (Averaged) | To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the number of participants using SABA rescue medication in Weeks 1-12 (individually) of the double-blind treatment period was assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for as-needed relief of asthma symptoms. |
| Participants Whose SABA Rescue Medication Use Increased Across Weeks 1-12 of the Treatment Period | Weeks 1-12 (Averaged) | To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the number of participants whose use of SABA rescue medication increased in Weeks 1-12 (individually) of the double-blind treatment period was assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for relief of asthma symptoms. |
| Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Baseline and Day 1, measured at 4 hr, 2 hr and 60, 30, 15, and 5 min, post-dose time points | The key secondary objective was to determine the onset of action for the efficacy of MF/F MDI 100/10 mcg BID, compared with MF MDI 100 mcg BID. The post-dose AM % predicted FEV1 was averaged sequentially, and the change from baseline on Day 1 was assessed. This key secondary endpoint was controlled for multiplicity in a step-down fashion, based on trial success defined as a statistically significant improvement in the primary endpoint for MF/F vs MF. Missing data were imputed using control-based multiple imputations with the cLDA model. |
| Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to Time of Last Measurable Concentration (AUC0-last) | Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 | Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment. |
| Maximum Plasma Concentration (Cmax) of Mometsone Furoate | Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 | Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment. |
| Time to Maximum Plasma Concentration (Tmax) of Mometsone Furoate | Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 | Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment. |
| Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to 12 Hours (AUC0-12) | Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 | Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment. |
| Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment | Baseline, Day 1 and Week 12 | This endpoint reflects changes in lung function data (forced expiratory volume in 1 second) measured across 0 to 4 hours post-dose on Day 1 and Week 12 compared to Baseline. Baseline was the average of 30 and 0 minutes pre-dose % predicted FEV1 values. The AUC was calculated over the scheduled timepoints of 0 min, 5 min, 15 min, 30 min, 60 min, 2 hr and 4 hr post-dose. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC. |
| Change From Baseline in AM Pre-Dose % Predicted FEV1 With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Baseline and Weeks 4, 8, and 12 (Averaged) | The change from baseline in AM pre-dose % predicted FEV1 with MF/F MDI 100/10 mcg BID vs MF MDI 100 mcg BID averaged over 12 weeks treatment was assessed. This secondary analysis of the change from baseline used the cLDA method without multiple imputation. A model-based MAR approach was used for missing data. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MF/F MDI 100/10 mcg BID MF/F administered by MDI, given as 100/10 mcg BID | 91 |
| MF MDI 100 mcg BID MF administered by MDI, given as 100 mcg BID | 90 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Parent/Guardian | 0 | 2 |
Baseline characteristics
| Characteristic | MF MDI 100 mcg BID | Total | MF/F MDI 100/10 mcg BID |
|---|---|---|---|
| Age, Continuous | 9.1 years STANDARD_DEVIATION 1.7 | 9.1 years STANDARD_DEVIATION 1.7 | 9.1 years STANDARD_DEVIATION 1.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants | 78 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 103 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 20 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 37 Participants | 70 Participants | 33 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 84 Participants | 43 Participants |
| Sex: Female, Male Female | 43 Participants | 89 Participants | 46 Participants |
| Sex: Female, Male Male | 47 Participants | 92 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 91 | 0 / 90 |
| other Total, other adverse events | 22 / 91 | 32 / 90 |
| serious Total, serious adverse events | 1 / 91 | 2 / 90 |
Outcome results
Primary
Change From Baseline in Morning (AM) Post-Dose % Predicted Forced Expiratory Volume in One Second (FEV1) in the Area Under the Curve (AUC)0-60
This endpoint reflects changes in lung function data (forced expiratory volume in 1 second) measured across 0 to 60 minutes post-dose (at 0, 5, 15, 30 and 60 minutes) and averaged across study visits in the Treatment Period (Day 1, Week 1, Week 4, Week 8 and Week 12) compared to Baseline. Baseline was the average of % predicted FEV1 values at 30 min and 0 min pre-dose. At each visit, the area under the curve is calculated over the post-dose timepoints. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC.
Time frame: Baseline, and average of Day 1, Weeks 1, 4, 8, and 12
Population: All participants who received at least one dose of randomized trial medication with at least one primary efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Change From Baseline in Morning (AM) Post-Dose % Predicted Forced Expiratory Volume in One Second (FEV1) in the Area Under the Curve (AUC)0-60 | Baseline | 79.21 Percent predicted FEV1 | Standard Deviation 11.44 |
| MF/F MDI 100/10 mcg BID | Change From Baseline in Morning (AM) Post-Dose % Predicted Forced Expiratory Volume in One Second (FEV1) in the Area Under the Curve (AUC)0-60 | Change from Baseline | 8.99 Percent predicted FEV1 | Standard Deviation 8.29 |
| MF MDI 100 mcg BID | Change From Baseline in Morning (AM) Post-Dose % Predicted Forced Expiratory Volume in One Second (FEV1) in the Area Under the Curve (AUC)0-60 | Baseline | 78.48 Percent predicted FEV1 | Standard Deviation 12.79 |
| MF MDI 100 mcg BID | Change From Baseline in Morning (AM) Post-Dose % Predicted Forced Expiratory Volume in One Second (FEV1) in the Area Under the Curve (AUC)0-60 | Change from Baseline | 3.96 Percent predicted FEV1 | Standard Deviation 5.92 |
p-value: <0.00195% CI: [3.21, 7.2]cLDA with multiple imputation
Primary
Count (Percentage) of Participants Discontinuing From Study Medication Due to An AE
An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Up to 24 weeks
Population: All randomized participants who received at least one dose of trial medication
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MF/F MDI 100/10 mcg BID | Count (Percentage) of Participants Discontinuing From Study Medication Due to An AE | 0 Participants |
| MF MDI 100 mcg BID | Count (Percentage) of Participants Discontinuing From Study Medication Due to An AE | 3 Participants |
| Total | Count (Percentage) of Participants Discontinuing From Study Medication Due to An AE | 3 Participants |
Primary
Count (Percentage) of Participants Experiencing At Least One Adverse Event (AE)
An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Up to 26 weeks
Population: All randomized participants who received at least one dose of trial medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MF/F MDI 100/10 mcg BID | Count (Percentage) of Participants Experiencing At Least One Adverse Event (AE) | 37 Participants |
| MF MDI 100 mcg BID | Count (Percentage) of Participants Experiencing At Least One Adverse Event (AE) | 52 Participants |
| Total | Count (Percentage) of Participants Experiencing At Least One Adverse Event (AE) | 89 Participants |
Secondary
Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to 12 Hours (AUC0-12)
Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
Time frame: Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
Population: Participants who consented to take part in the PK sub-trial and had evaluable data for AUC(0-12).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to 12 Hours (AUC0-12) | 109 hr*pg/mL | Geometric Coefficient of Variation 55.8 |
Secondary
Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to Time of Last Measurable Concentration (AUC0-last)
Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
Time frame: Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
Population: Participants who consented to take part in the PK sub-trial and had evaluable data for AUC(0-last).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to Time of Last Measurable Concentration (AUC0-last) | 106 hr*pg/mL | Geometric Coefficient of Variation 53.5 |
Secondary
Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment
The key secondary objective was to determine the onset of action for the efficacy of MF/F MDI 100/10 mcg BID, compared with MF MDI 100 mcg BID. The post-dose AM % predicted FEV1 was averaged sequentially, and the change from baseline on Day 1 was assessed. This key secondary endpoint was controlled for multiplicity in a step-down fashion, based on trial success defined as a statistically significant improvement in the primary endpoint for MF/F vs MF. Missing data were imputed using control-based multiple imputations with the cLDA model.
Time frame: Baseline and Day 1, measured at 4 hr, 2 hr and 60, 30, 15, and 5 min, post-dose time points
Population: All participants who received at least one dose of randomized trial medication with at least one efficacy evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Baseline | 79.21 Percent predicted FEV1 | Standard Deviation 11.44 |
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (4 hr post-dose on Day 1) | 11.61 Percent predicted FEV1 | Standard Deviation 10.31 |
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (2 hr post-dose on Day 1) | 12.71 Percent predicted FEV1 | Standard Deviation 9.53 |
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (60 min post-dose on Day 1) | 11.05 Percent predicted FEV1 | Standard Deviation 8.51 |
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (30 min post-dose on Day 1) | 9.56 Percent predicted FEV1 | Standard Deviation 7.02 |
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (15 min post-dose on Day 1) | 8.00 Percent predicted FEV1 | Standard Deviation 7.12 |
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (5 min post-dose on Day 1) | 5.20 Percent predicted FEV1 | Standard Deviation 6.93 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (4 hr post-dose on Day 1) | 5.68 Percent predicted FEV1 | Standard Deviation 7.38 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Baseline | 78.48 Percent predicted FEV1 | Standard Deviation 12.79 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (30 min post-dose on Day 1) | 3.05 Percent predicted FEV1 | Standard Deviation 4.99 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (5 min post-dose on Day 1) | 0.95 Percent predicted FEV1 | Standard Deviation 4.33 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (2 hr post-dose on Day 1) | 5.87 Percent predicted FEV1 | Standard Deviation 6.52 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (15 min post-dose on Day 1) | 1.38 Percent predicted FEV1 | Standard Deviation 4.42 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | Change from Baseline (60 min post-dose on Day 1) | 4.92 Percent predicted FEV1 | Standard Deviation 6.06 |
p-value: <0.00195% CI: [3.53, 8.56]cLDA with multiple imputation
p-value: <0.00195% CI: [4.74, 9.35]cLDA with multiple imputation
p-value: <0.00195% CI: [4.09, 8.28]cLDA with multiple imputation
p-value: <0.00195% CI: [5.1, 8.67]cLDA with multiple imputation
p-value: <0.00195% CI: [4.89, 8.39]cLDA with multiple imputation
p-value: <0.00195% CI: [2.5, 5.91]cLDA with multiple imputation
Secondary
Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment
This endpoint reflects changes in lung function data (forced expiratory volume in 1 second) measured across 0 to 4 hours post-dose on Day 1 and Week 12 compared to Baseline. Baseline was the average of 30 and 0 minutes pre-dose % predicted FEV1 values. The AUC was calculated over the scheduled timepoints of 0 min, 5 min, 15 min, 30 min, 60 min, 2 hr and 4 hr post-dose. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC.
Time frame: Baseline, Day 1 and Week 12
Population: All participants who received at least one dose of randomized trial medication with at least one efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment | Baseline | 79.21 Percent predicted FEV1 | Standard Deviation 11.44 |
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment | Change from Baseline on Day 1 | 7.13 Percent predicted FEV1 | Standard Deviation 5.35 |
| MF/F MDI 100/10 mcg BID | Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment | Change from Baseline at Week 12 | 7.56 Percent predicted FEV1 | Standard Deviation 11.2 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment | Baseline | 78.48 Percent predicted FEV1 | Standard Deviation 12.79 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment | Change from Baseline on Day 1 | 2.70 Percent predicted FEV1 | Standard Deviation 3.09 |
| MF MDI 100 mcg BID | Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment | Change from Baseline at Week 12 | 4.87 Percent predicted FEV1 | Standard Deviation 7.72 |
p-value: <0.00195% CI: [4.36, 8.27]cLDA
p-value: 0.02695% CI: [0.41, 6.26]cLDA
Secondary
Change From Baseline in AM Pre-Dose % Predicted FEV1 With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment
The change from baseline in AM pre-dose % predicted FEV1 with MF/F MDI 100/10 mcg BID vs MF MDI 100 mcg BID averaged over 12 weeks treatment was assessed. This secondary analysis of the change from baseline used the cLDA method without multiple imputation. A model-based MAR approach was used for missing data.
Time frame: Baseline and Weeks 4, 8, and 12 (Averaged)
Population: All participants who received at least one dose of randomized trial medication with at least one efficacy evaluation across the treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Change From Baseline in AM Pre-Dose % Predicted FEV1 With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Baseline | 79.21 Percent predicted FEV1 | Standard Deviation 11.44 |
| MF/F MDI 100/10 mcg BID | Change From Baseline in AM Pre-Dose % Predicted FEV1 With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Change from Baseline (Weeks 4, 8, and 12) | 1.51 Percent predicted FEV1 | Standard Deviation 7.15 |
| MF MDI 100 mcg BID | Change From Baseline in AM Pre-Dose % Predicted FEV1 With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Baseline | 78.22 Percent predicted FEV1 | Standard Deviation 12.93 |
| MF MDI 100 mcg BID | Change From Baseline in AM Pre-Dose % Predicted FEV1 With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Change from Baseline (Weeks 4, 8, and 12) | 0.44 Percent predicted FEV1 | Standard Deviation 5.49 |
p-value: 0.19795% CI: [-0.85, 4.11]cLDA
Secondary
Maximum Plasma Concentration (Cmax) of Mometsone Furoate
Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
Time frame: Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
Population: Participants who consented to take part in the PK sub-trial and had evaluable data for Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Maximum Plasma Concentration (Cmax) of Mometsone Furoate | 16 pg/mL | Geometric Coefficient of Variation 68.2 |
Secondary
Mean Change From Baseline in Total Daily Use of Short-Acting Beta-Agonist (SABA) Rescue Medication With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment
To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the change from baseline in total daily short-acting beta-agonist (SABA) use (puffs per day) was averaged and assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for as-needed relief of asthma symptoms. This secondary analysis of the change from baseline used the cLDA method without multiple imputation.A model-based MAR approach was used for missing data.
Time frame: Baseline and Weeks 1-12 (Averaged)
Population: All participants who received at least one dose of randomized trial medication with at least one efficacy evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Mean Change From Baseline in Total Daily Use of Short-Acting Beta-Agonist (SABA) Rescue Medication With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Baseline | 0.25 Puffs per day | Standard Deviation 0.66 |
| MF/F MDI 100/10 mcg BID | Mean Change From Baseline in Total Daily Use of Short-Acting Beta-Agonist (SABA) Rescue Medication With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Change from Baseline Over Weeks 1-12 (Average) | -0.12 Puffs per day | Standard Deviation 0.58 |
| MF MDI 100 mcg BID | Mean Change From Baseline in Total Daily Use of Short-Acting Beta-Agonist (SABA) Rescue Medication With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Baseline | 0.13 Puffs per day | Standard Deviation 0.5 |
| MF MDI 100 mcg BID | Mean Change From Baseline in Total Daily Use of Short-Acting Beta-Agonist (SABA) Rescue Medication With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment | Change from Baseline Over Weeks 1-12 (Average) | -0.02 Puffs per day | Standard Deviation 0.52 |
Secondary
Participants Using SABA Rescue Medication Across Weeks 1-12 of the Treatment Period
To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the number of participants using SABA rescue medication in Weeks 1-12 (individually) of the double-blind treatment period was assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for as-needed relief of asthma symptoms.
Time frame: Baseline and Weeks 1-12 (Averaged)
Population: Data were provided for all participants who received at least one dose of randomized trial medication and had at least one efficacy evaluation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MF/F MDI 100/10 mcg BID | Participants Using SABA Rescue Medication Across Weeks 1-12 of the Treatment Period | Baseline | 23 Participants |
| MF/F MDI 100/10 mcg BID | Participants Using SABA Rescue Medication Across Weeks 1-12 of the Treatment Period | Weeks 1-12 | 41 Participants |
| MF MDI 100 mcg BID | Participants Using SABA Rescue Medication Across Weeks 1-12 of the Treatment Period | Baseline | 17 Participants |
| MF MDI 100 mcg BID | Participants Using SABA Rescue Medication Across Weeks 1-12 of the Treatment Period | Weeks 1-12 | 45 Participants |
Secondary
Participants Whose SABA Rescue Medication Use Increased Across Weeks 1-12 of the Treatment Period
To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the number of participants whose use of SABA rescue medication increased in Weeks 1-12 (individually) of the double-blind treatment period was assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for relief of asthma symptoms.
Time frame: Weeks 1-12 (Averaged)
Population: Data were provided for all participants who received at least one dose of randomized trial medication and had at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MF/F MDI 100/10 mcg BID | Participants Whose SABA Rescue Medication Use Increased Across Weeks 1-12 of the Treatment Period | 24 Participants |
| MF MDI 100 mcg BID | Participants Whose SABA Rescue Medication Use Increased Across Weeks 1-12 of the Treatment Period | 34 Participants |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Mometsone Furoate
Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
Time frame: Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
Population: Participants who consented to take part in the PK sub-trial and had evaluable data for Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MF/F MDI 100/10 mcg BID | Time to Maximum Plasma Concentration (Tmax) of Mometsone Furoate | 1.47 hr |