Once-daily evening dosing of mometasone furoate administered via a dry powder inhaler does not adversely affect the hypothalamic-pituitary-adrenal axis.
BACKGROUND
Inhaled corticosteroids can suppress the hypothalamic-pituitary-adrenal (HPA) axis with long-term exposure. This study reports the effects of moderate-dose (400 microg) mometasone furoate administered via dry powder inhaler (MF-DPI) once daily in the evening on the HPA axis in adults with mild to moderate asthma.


METHODS
In this randomized, investigator-blind, placebo-controlled trial, nonsmoking adults aged 18 to 50 years with mild-to-moderate asthma received once-daily MF-DPI 400 microg (2 x 200 microg/inhalation; treatment A), MF-DPI 400 microg (1 x 400 microg/inhalation; treatment B), or placebo (two inhalations, treatment C), delivered at approximately 8:00 pm, for 42 days. Primary end points were area under the serum cortisol concentration-vs-time curve over 24 h (AUC(0-24)), 24-h urinary free cortisol (creatinine corrected) on day 42, maximum serum cortisol concentration (C(max)), time to C(max) (T(max)), and 8 :00 am serum cortisol concentration. This study was initiated April 16, 2001 and completed June 14, 2001.


RESULTS
Serum cortisol AUC(0-24), C(max), and 24-h urinary free cortisol levels decreased with all treatments by day 42 with no significant differences between groups. For treatment B, the change in 8:00 am serum cortisol from baseline to day 42 was significantly less than placebo (P = .04), attributed to a large baseline difference between these treatments. A significant difference in T(max) change from baseline by day 42 for treatment B compared with the other treatments (P = .019) was also attributed to significant baseline differences between groups. Actual values at day 42 for T(max) and 8:00 am serum cortisol were not significantly different between treatment groups (P > or = .275).


CONCLUSIONS
Once-evening moderate dosing (400 microg) MF-DPI does not suppress HPA axis function in adults with mild to moderate asthma.
Kosoglou
Teddy
T
Early Clinical Research & Experimental Medicine, Schering-Plough Research Institute, 2015 Galloping Hill Road (K-15-4, 4455), Kenilworth, NJ 07033, USA. teddy.kosoglou@spcorp.com
Cutler
David L
DL
Staudinger
Heribert
H
Herron
Jerry M
JM
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D018926:Anti-Allergic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D000068656:Mometasone Furoate; D009330:Nebulizers and Vaporizers; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011244:Pregnadienediols / Q000008:administration & dosage*; D011863:Radioimmunoassay; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult
D018926:Anti-Allergic Agents; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D006854:Hydrocortisone