A Study of Mometasone Furoate Metered Dose Inhaler in Children With Persistent Asthma (P04223)

• Mometasone Furoate (MF) Metered Dose Inhaler (MDI), 25 mcg (Drug): MF MDI 25 mcg (per inhalation), 2 puffs BID for 12 weeks
• Mometasone Furoate (MF) Metered Dose Inhaler (MDI), 50 mcg (Drug): MF MDI 50 mcg (per inhalation), 2 puffs BID for 12 weeks
• Mometasone Furoate (MF) Metered Dose Inhaler (MDI), 100 mcg (Drug): MF MDI 100 mcg (per inhalation), 2 puffs BID for 12 weeks
• Mometasone Furoate (MF) Dry Powder Inhaler (DPI), 100 mcg (Drug), also known as Asmanex® Twisthaler®: MF DPI 100 mcg (per inhalation), 1 puff QD for 12 weeks
• Placebo Metered Dose Inhaler (MDI) (Drug): Placebo MDI, 2 puffs BID for 12 weeks
• Placebo Dry Powder Inhaler (DPI) (Drug): Placebo DPI, 1 puff QD for 12 weeks

Primary outcomes

• 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 outcomes

• 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.

Sex: All, ages: 5 Years to 11 Years

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.

Participant flow

Outcome results

• Change From Baseline in Percent Predicted Morning (AM) Forced Expiratory Volume in 1 Second (FEV1) - MF MDI vs. Placebo (Primary), Least squares mean, Percentage of Predicted FEV1: MF MDI 50 mcg BID 4.52 (2.32 to 6.72); MF MDI 100 mcg BID 6.95 (4.73 to 9.16); MF MDI 200 mcg BID 6.00 (3.74 to 8.25); Placebo 0.66 (-1.72 to 3.03) (p 0.019)
• Change From Baseline in AM Peak Expiratory Flow (PEF) - MF MDI vs. Placebo (Secondary), Least squares mean, Liters/minute: MF MDI 50 mcg BID 17.83 (5.35 to 30.3); MF MDI 100 mcg BID 26.03 (13.55 to 38.51); MF MDI 200 mcg BID 16.68 (4.50 to 28.86); Placebo -1.32 (-15.49 to 12.85); MF DPI 100 mcg QD -0.92 (-12.82 to 10.99) (p 0.045)
• Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities (PAQLQ(S)) Total Score - MF MDI vs. Placebo (Secondary), Least squares mean, Score on a Scale: MF MDI 50 mcg BID 0.35 (0.23 to 0.48); MF MDI 100 mcg BID 0.38 (0.25 to 0.50); MF MDI 200 mcg BID 0.44 (0.31 to 0.56); Placebo 0.26 (0.12 to 0.39); MF DPI 100 mcg QD 0.47 (0.35 to 0.59) (p 0.280)
• Change From Baseline in Percent Predicted AM FEV1 - MF MDI 50 mcg BID vs. MF DPI 100 mcg QD (Secondary), Least squares mean, Percentage of Predicted FEV1: MF MDI 50 mcg BID 4.52 (2.32 to 6.72); MF DPI 100 mcg QD 3.13 (1.01 to 5.25) (p 0.368)

Adverse events

Time frame: Up to 12 weeks

Serious adverse events by term

Other adverse events by term

• Results publication: Amar NJ, Shekar T, Varnell TA, Mehta A, Philip G. Mometasone furoate (MF) improves lung function in pediatric asthma: A double-blind, randomized controlled dose-ranging trial of MF metered-dose inhaler. Pediatr Pulmonol. 2017 Mar;52(3):310-318. doi: 10.1002/ppul.23563. Epub 2016 Oct 14. PMID 27740721

• Medical Director, Study director, Merck Sharp & Dohme LLC

NIH grants: 2008