Asthma
Conditions
Keywords
Asthma, Children, Persistent
Brief summary
The primary objective of this study is to demonstrate the dose-related efficacy, by evaluating morning (AM) lung function at the end of the dosing interval (AM pre-dose percent predicted forced expiratory volume in one second \[FEV1\]) across 12 weeks of treatment, of three doses (50 mcg, 100 mcg, and 200 mcg) of Mometasone Furoate (MF) Metered Dose Inhaler (MDI) twice a day (BID) compared with Placebo in children 5 to 11 years of age, inclusive, with persistent asthma. The primary hypothesis of this study is that at least one dose of MF MDI BID increases lung function, defined as a significant increase in percent predicted FEV1, when compared to Placebo.
Interventions
DRUGMometasone Furoate (MF) Metered Dose Inhaler (MDI), 25 mcg
MF MDI 25 mcg (per inhalation), 2 puffs BID for 12 weeks
DRUGMometasone Furoate (MF) Metered Dose Inhaler (MDI), 50 mcg
MF MDI 50 mcg (per inhalation), 2 puffs BID for 12 weeks
MF MDI 100 mcg (per inhalation), 2 puffs BID for 12 weeks
DRUGMometasone Furoate (MF) Dry Powder Inhaler (DPI), 100 mcg
MF DPI 100 mcg (per inhalation), 1 puff QD for 12 weeks
DRUGPlacebo Metered Dose Inhaler (MDI)
Placebo MDI, 2 puffs BID for 12 weeks
DRUGPlacebo Dry Powder Inhaler (DPI)
Placebo DPI, 1 puff QD for 12 weeks
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of asthma of at least 6 months duration. * Using an Inhaled corticosteroid (ICS), either alone or in combination with a long-acting beta-2 agonist (LABA), for at least 12 weeks prior to the Screening Visit and must have been on a stable asthma regimen for at least 2 weeks prior to the Screening Visit, must not have used oral glucocorticosteroids within 30 days of the Screening Visit.
Exclusion criteria
* Treated in the emergency room for a severe asthma exacerbation requiring systemic glucocorticosteroid treatment, or hospitalization for management of airway obstruction within 3 months prior to the Screening Visit. * History of ventilator support for respiratory failure secondary to asthma. * Upper or lower respiratory tract infection (viral or bacterial) within the 2 weeks prior to Screening and Baseline Visits. * History of clinically significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular, or other significant medical illness or disorder which, in the judgment of the investigator, could interfere with the study or require treatment that might interfere with the study. Specific examples include but are not limited to insulin-dependent diabetes, hypertension, active hepatitis, cardiovascular disease including hypertension, or conditions that may interfere with respiratory function such as, bronchiectasis, and cystic fibrosis. Other conditions that are well controlled and stable will not prohibit participation if deemed appropriate per the investigator's judgment. * Inability to correctly use an oral MDI or a DPI. * Participation in this study at another investigational site. Participation in a different investigational study at any site during the same time frame of this study. * Randomization into this study more than once. * Direct association with either the administration of the this study or the study staff.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent Predicted Morning (AM) Forced Expiratory Volume in 1 Second (FEV1) - MF MDI vs. Placebo | Baseline and Week 12 | FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. The percent predicted FEV1 equals the participant's observed FEV1 divided by the participant's predicted FEV1 (determined by height and race) and converted to a percentage by multiplying by 100%. The goal of the primary outcome measure was to compare the change from Baseline in AM FEV1 between the MF MDI and Placebo treatment groups. The comparison between the MF MDI 50 mcg BID vs. MF DPI 100 mcg QD treatment groups is presented in a subsequent outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in AM Peak Expiratory Flow (PEF) - MF MDI vs. Placebo | Baseline and Week 12 | PEF, measured in liters per minute, is the highest flow during exhalation. Participants recorded diary entries for PEF twice daily (in the morning upon rising and in the evening at bedtime). The goal of the secondary outcome measure was to compare the change from Baseline in AM PEF between the MF MDI and Placebo treatment groups. |
| Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities (PAQLQ(S)) Total Score - MF MDI vs. Placebo | Baseline and Week 12 | The PAQLQ(S) consists of 23 questions in 3 categories: Symptoms (10 items), Activity Limitations (5 items), and Emotional Function (8 items). Responses are based on a 7-point scale (7=not bothered at all to 1=extremely bothered). PAQLQ(S) Total Scores could range from 23 to 161, with a lower score indicating a lower quality of life. The PAQLQ(S) included only participants in participating countries in which a validated translated questionnaire was available. The goal of the secondary outcome measure was to compare the change from Baseline in PAQLQ(S) between the MF MDI and Placebo treatment groups. |
| Change From Baseline in Percent Predicted AM FEV1 - MF MDI 50 mcg BID vs. MF DPI 100 mcg QD | Baseline and Week 12 | FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. The percent predicted FEV1 equals the participant's observed FEV1 divided by the participant's predicted FEV1 (determined by height and race) and converted to a percentage by multiplying by 100%. The goal of the secondary outcome measure was to compare the change from Baseline in AM FEV1 between the MF MDI 50 mcg BID and MF DPI 100 mcg QD treatment groups. The comparisons between the other MF MDI BID and Placebo treatment groups are presented in a previous outcome measure. |
Participant flow
Pre-assignment details
A total of 583 participants were randomized; 5 participants were randomized in error and did not receive any doses of randomized study drug.
Participants by arm
| Arm | Count |
|---|---|
| MF MDI 50 mcg BID Participants receive MF MDI 25 mcg x 2 inhalations (50 mcg total dose) BID PLUS Placebo DPI x 1 inhalation QD in the evening for 12 weeks. | 120 |
| MF MDI 100 mcg BID Participants receive MF MDI 50 mcg x 2 inhalations (100 mcg total dose) BID PLUS Placebo DPI x 1 inhalation QD in the evening for 12 weeks. | 113 |
| MF MDI 200 mcg BID Participants receive MF MDI 100 mcg x 2 inhalations (200 mcg total dose) BID PLUS Placebo DPI x 1 inhalation QD in the evening for 12 weeks. | 108 |
| MF DPI 100 mcg QD Participants receive Placebo MDI x 2 inhalations BID PLUS MF DPI x 1 inhalation QD in the evening for 12 weeks. | 125 |
| Placebo Participants receive Placebo MDI x 2 inhalations BID PLUS Placebo DPI x 1 inhalation QD in the evening for 12 weeks. | 112 |
| Total | 578 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 0 | 4 | 3 |
| Overall Study | Excluded Medication | 0 | 1 | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 3 | 2 | 2 | 4 |
| Overall Study | Noncompliance with Study Drug | 0 | 0 | 1 | 2 | 1 |
| Overall Study | Physician Decision | 3 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 9 | 5 | 6 | 5 | 10 |
| Overall Study | Technical Problems | 1 | 0 | 2 | 4 | 1 |
| Overall Study | Treatment Failure | 22 | 20 | 12 | 19 | 30 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | MF MDI 50 mcg BID | MF MDI 100 mcg BID | MF MDI 200 mcg BID | MF DPI 100 mcg QD | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 8.7 Years STANDARD_DEVIATION 1.7 | 8.6 Years STANDARD_DEVIATION 1.9 | 8.7 Years STANDARD_DEVIATION 1.7 | 8.7 Years STANDARD_DEVIATION 1.7 | 9.0 Years STANDARD_DEVIATION 1.7 | 8.8 Years STANDARD_DEVIATION 1.8 |
| Sex: Female, Male Female | 51 Participants | 44 Participants | 59 Participants | 48 Participants | 30 Participants | 232 Participants |
| Sex: Female, Male Male | 69 Participants | 69 Participants | 49 Participants | 77 Participants | 82 Participants | 346 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 120 | 18 / 113 | 18 / 108 | 16 / 125 | 19 / 112 |
| serious Total, serious adverse events | 2 / 120 | 1 / 113 | 2 / 108 | 4 / 125 | 2 / 112 |
Outcome results
Primary
Change From Baseline in Percent Predicted Morning (AM) Forced Expiratory Volume in 1 Second (FEV1) - MF MDI vs. Placebo
FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. The percent predicted FEV1 equals the participant's observed FEV1 divided by the participant's predicted FEV1 (determined by height and race) and converted to a percentage by multiplying by 100%. The goal of the primary outcome measure was to compare the change from Baseline in AM FEV1 between the MF MDI and Placebo treatment groups. The comparison between the MF MDI 50 mcg BID vs. MF DPI 100 mcg QD treatment groups is presented in a subsequent outcome measure.
Time frame: Baseline and Week 12
Population: The Full Analysis Set (FAS) population consisted of all participants who received ≥1 study drug dose and had a Baseline or ≥1 post-randomization value for this outcome measure. Only participants who received MF MDI or Placebo were included in this primary analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MF MDI 50 mcg BID | Change From Baseline in Percent Predicted Morning (AM) Forced Expiratory Volume in 1 Second (FEV1) - MF MDI vs. Placebo | 4.52 Percentage of Predicted FEV1 |
| MF MDI 100 mcg BID | Change From Baseline in Percent Predicted Morning (AM) Forced Expiratory Volume in 1 Second (FEV1) - MF MDI vs. Placebo | 6.95 Percentage of Predicted FEV1 |
| MF MDI 200 mcg BID | Change From Baseline in Percent Predicted Morning (AM) Forced Expiratory Volume in 1 Second (FEV1) - MF MDI vs. Placebo | 6.00 Percentage of Predicted FEV1 |
| Placebo | Change From Baseline in Percent Predicted Morning (AM) Forced Expiratory Volume in 1 Second (FEV1) - MF MDI vs. Placebo | 0.66 Percentage of Predicted FEV1 |
Comparison: Change from Baseline in percent predicted FEV1 at Week 12: MF MDI 50 mcg BID vs. Placebop-value: 0.01995% CI: [0.64, 7.09]cLDA model
Comparison: Change from Baseline in percent predicted FEV1 at Week 12: MF MDI 100 mcg BID vs. Placebop-value: <0.00195% CI: [3.05, 9.53]cLDA
Comparison: Change from Baseline in percent predicted FEV1 at Week 12: MF MDI 200 mcg BID vs. Placebop-value: 0.00195% CI: [2.07, 8.61]cLDA
Secondary
Change From Baseline in AM Peak Expiratory Flow (PEF) - MF MDI vs. Placebo
PEF, measured in liters per minute, is the highest flow during exhalation. Participants recorded diary entries for PEF twice daily (in the morning upon rising and in the evening at bedtime). The goal of the secondary outcome measure was to compare the change from Baseline in AM PEF between the MF MDI and Placebo treatment groups.
Time frame: Baseline and Week 12
Population: The FAS population consisted of all participants who received ≥1 study drug dose and had a Baseline or ≥1 post-randomization value for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MF MDI 50 mcg BID | Change From Baseline in AM Peak Expiratory Flow (PEF) - MF MDI vs. Placebo | 17.83 Liters/minute |
| MF MDI 100 mcg BID | Change From Baseline in AM Peak Expiratory Flow (PEF) - MF MDI vs. Placebo | 26.03 Liters/minute |
| MF MDI 200 mcg BID | Change From Baseline in AM Peak Expiratory Flow (PEF) - MF MDI vs. Placebo | 16.68 Liters/minute |
| Placebo | Change From Baseline in AM Peak Expiratory Flow (PEF) - MF MDI vs. Placebo | -1.32 Liters/minute |
| MF DPI 100 mcg QD | Change From Baseline in AM Peak Expiratory Flow (PEF) - MF MDI vs. Placebo | -0.92 Liters/minute |
Comparison: Change from Baseline in AM PEF: MF MDI 50 mcg BID vs. Placebo. Only participants who received MF MDI or Placebo were included in the statistical analysis.p-value: 0.04595% CI: [0.43, 37.87]cLDA
Comparison: Change from Baseline in AM PEF: MF MDI 100 mcg BID vs. Placebo. Only participants who received MF MDI or Placebo were included in the statistical analysis.p-value: 0.00495% CI: [8.63, 46.08]cLDA
Comparison: Change from Baseline in AM PEF: MF MDI 200 mcg BID vs. Placebo. Only participants who received MF MDI or Placebo were included in the statistical analysis.p-value: 0.05795% CI: [-0.51, 36.53]cLDA
Secondary
Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities (PAQLQ(S)) Total Score - MF MDI vs. Placebo
The PAQLQ(S) consists of 23 questions in 3 categories: Symptoms (10 items), Activity Limitations (5 items), and Emotional Function (8 items). Responses are based on a 7-point scale (7=not bothered at all to 1=extremely bothered). PAQLQ(S) Total Scores could range from 23 to 161, with a lower score indicating a lower quality of life. The PAQLQ(S) included only participants in participating countries in which a validated translated questionnaire was available. The goal of the secondary outcome measure was to compare the change from Baseline in PAQLQ(S) between the MF MDI and Placebo treatment groups.
Time frame: Baseline and Week 12
Population: The FAS population consisted of all participants who received ≥1 study drug dose and had a Baseline or ≥1 post-randomization value for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MF MDI 50 mcg BID | Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities (PAQLQ(S)) Total Score - MF MDI vs. Placebo | 0.35 Score on a Scale |
| MF MDI 100 mcg BID | Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities (PAQLQ(S)) Total Score - MF MDI vs. Placebo | 0.38 Score on a Scale |
| MF MDI 200 mcg BID | Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities (PAQLQ(S)) Total Score - MF MDI vs. Placebo | 0.44 Score on a Scale |
| Placebo | Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities (PAQLQ(S)) Total Score - MF MDI vs. Placebo | 0.26 Score on a Scale |
| MF DPI 100 mcg QD | Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities (PAQLQ(S)) Total Score - MF MDI vs. Placebo | 0.47 Score on a Scale |
Comparison: Change from Baseline in PAQLQ(S) Total Score: MF MDI 50 mcg BID vs. Placebo. Only participants who received MF MDI or Placebo were included in the statistical analysis.p-value: 0.2895% CI: [-0.08, 0.27]cLDA
Comparison: Change from Baseline in PAQLQ(S) Total Score: MF MDI 100 mcg BID vs. Placebo. Only participants who received MF MDI or Placebo were included in the statistical analysis.p-value: 0.17895% CI: [-0.06, 0.3]cLDA
Comparison: Change from Baseline in PAQLQ(S) Total Score: MF MDI 200 mcg BID vs. Placebo. Only participants who received MF MDI or Placebo were included in the statistical analysis.p-value: 0.04595% CI: [0, 0.36]cLDA
Secondary
Change From Baseline in Percent Predicted AM FEV1 - MF MDI 50 mcg BID vs. MF DPI 100 mcg QD
FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. The percent predicted FEV1 equals the participant's observed FEV1 divided by the participant's predicted FEV1 (determined by height and race) and converted to a percentage by multiplying by 100%. The goal of the secondary outcome measure was to compare the change from Baseline in AM FEV1 between the MF MDI 50 mcg BID and MF DPI 100 mcg QD treatment groups. The comparisons between the other MF MDI BID and Placebo treatment groups are presented in a previous outcome measure.
Time frame: Baseline and Week 12
Population: The FAS population consisted of all participants who received ≥1 study drug dose and had a Baseline or ≥1 post-randomization value for this outcome measure. Only participants who received MF MDI 50 mcg or MF DPI were included in this secondary analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MF MDI 50 mcg BID | Change From Baseline in Percent Predicted AM FEV1 - MF MDI 50 mcg BID vs. MF DPI 100 mcg QD | 4.52 Percentage of Predicted FEV1 |
| MF MDI 100 mcg BID | Change From Baseline in Percent Predicted AM FEV1 - MF MDI 50 mcg BID vs. MF DPI 100 mcg QD | 3.13 Percentage of Predicted FEV1 |
Comparison: Change from Baseline in percent predicted FEV1 at Week 12: MF MDI 50 mcg BID vs. MF DPI 100 mcg QD. Only participants who received MF MDI 50 mcg BID or MF DPI 100 mcg QD were included in the statistical analysis.p-value: 0.36895% CI: [-1.65, 4.44]cLDA model