PURPOSE: Inhaled corticosteroids (ICSs) have proven efficacy and are well tolerated in the treatment of asthma, but they can interfere with the activity of the hypothalamic-pituitary-adrenal (HPA) axis and lead to cortisol suppression. The effects of mometasone furoate dry powder inhaler (MF-DPI) administered once daily in the evening (QD PM) on serum and urinary cortisol levels were evaluated in a safety study.
METHODS: A randomized, investigator-blind, placebo-controlled, parallel-group study enrolled 48 ICS-naïve adults (18–50y) with mild-to-moderate asthma. At screening, eligible subjects had FEV1 values of 60%–80% predicted and morning serum cortisol levels of 5–25μg/dL. Subjects (n=16/treatment) were randomized to receive MF-DPI 400μg (2×200μg), MF-DPI 400μg (1×400μg), or placebo QD at approximately 8PM for 42 consecutive days. Blood samples were taken at specified times and urine was collected for 24 hours at baseline and day 42. Primary endpoints were the changes from baseline in the 24-hour area under the serum cortisol concentration vs time curve (AUC 0-24) and the creatinine-corrected 24-hour urine free cortisol excretion. Adverse events and vital signs were also monitored.
RESULTS: Subjects in all 3 treatment groups had similar serum cortisol levels and urinary cortisol excretion at baseline. Changes from baseline in serum cortisol AUC 0-24 values on day 42 were -27.0, -29.9, and -31.2μg•h/dL in the MF-DPI 400μg (2×200μg), MF-DPI 400μg (1×400μg), and placebo groups, respectively. Changes from baseline in 24-hour urine free cortisol were -4.2, -8.3, and -7.4μg/g creatinine in the MF-DPI 400μg (2×200μg), MF-DPI 400μg (1×400μg), and placebo groups, respectively. None of the differences between treatments in these safety endpoints were statistically significant. Headache was the most common adverse event, and no serious or life-threatening adverse events occurred.
CONCLUSION: Treatment with MF-DPI 400μg QD PM for 42 consecutive days had no significant effect on serum cortisol concentrations or urine free cortisol excretion.
CLINICAL IMPLICATIONS: Once-daily administration of MF-DPI does not have a significant effect on cortisol concentrations in subjects with mild-to-moderate asthma.
DISCLOSURE: Teddy Kosoglou, No Product/Research Disclosure Information; Employee Schering-Plough employee.