PURPOSE: Assessing systemic effects that inhaled corticosteroids may exert in children with asthma is of great importance. We report findings from a pediatric study investigating the effects of mometasone furoate dry-powder inhaler (MF-DPI) on the hypothalamic-pituitary-adrenal axis. Unlike previously published investigations in children, systemic effects were monitored in a strictly controlled hospital inpatient setting.
METHODS: The systemic effects of MF-DPI treatment were investigated in a randomized, placebo-controlled 29-day trial. Fifty children (6–11 yrs old) with mild asthma were randomized to twice-daily (BID) treatment with MF-DPI (100μg, n=13; 200μg, n=13; 400μg, n=12) or placebo (n=12). The primary endpoint was the change in the 12-hour plasma cortisol area under the curve (AUC; calculated between 10PM and 10AM in a hospital inpatient setting) from baseline to day 28/29. Data were analyzed using analysis of covariance with baseline as covariate and treatment as fixed effect.
RESULTS: Of the 50 subjects who were randomized, 42 subjects were in the primary analysis subset (MF-DPI 100μg BID, n=12; MF-DPI 200μg BID, n=12; MF-DPI 400μg BID, n=11; placebo, n=7). Treatment with MF-DPI 100μg BID and placebo had similar effects on the 12-hour plasma cortisol AUC. Numerical decreases from baseline were observed for MF-DPI 200μg BID (P=0.078 vs placebo) and MF-DPI 400μg BID groups (P=0.050 vs placebo). On day 29, changes from baseline in the 12-hour plasma cortisol AUC were: 3.23, 1.83, –24.11, and –22.69 μg•h/dL for placebo, MF-DPI 100, 200, and 400μg BID, respectively. All MF-DPI treatments were well tolerated. The most common treatment-emergent adverse events (AEs) were headache, fever, allergy aggravated, chest pain, and pharyngitis (reported in ≥10% of subjects in at least 1 group). No serious AEs or discontinuations because of AEs were reported.
CONCLUSION: As measured by plasma cortisol levels in children with asthma, MF-DPI 100μg BID was comparable to placebo; MF-DPI 200μg BID was not significantly different from placebo; and MF-DPI 400μg BID was marginally significantly different from placebo.
CLINICAL IMPLICATIONS: This study demonstrates the systemic safety of MF-DPI in children.
DISCLOSURE: David Skoner, Consultant fee, speaker bureau, advisory committee, etc. Schering-Plough Laboratories; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Mometasone furoate dry powder inhaler is currently not approved for use in pediatric patients aged less than 12 years.