SESSION TYPE: Asthma Treatment
PRESENTED ON: Monday, October 22, 2012 at 11:15 AM - 12:30 PM
PURPOSE: This study was conducted to compare effects of inhaled corticosteroids MF and FP on the hypothalamic-pituitary-adrenal (HPA) axis when administered from combination MDI products in patients with asthma.
METHODS: In a randomized, open-label, placebo-controlled, parallel-group study 66 patients with mild-to-moderate asthma received oral inhalations of one of the following 4 treatments administered twice-daily (BID) via MDI for 42 days: MF/F 200μg/10μg (Treatment A); MF/F 400μg/10μg (Treatment B); FP/S 460μg/42μg (Treatment C); or placebo (Treatment D). Plasma cortisol concentrations were measured over 24 hours on Days -1 (Baseline) and 42. Least-squares (LS) mean change from Baseline to Day 42 in 24-hr plasma cortisol AUC (primary endpoint) was analyzed via ANOVA. Geometric mean ratio (GMR) and 90% confidence interval (90%CI) for change from baseline in AUC was calculated for each treatment comparison. If 90%CI for the GMRs fell within the 70%-143% range the treatments were deemed comparable.
RESULTS: Mean baseline 24-hr cortisol AUCs were similar across groups. The LS mean (90%CI) cortisol AUC Day 42/Day 1 ratio for Treatments A, B, C and D were 99% (87%-113%), 84% (75%-95%), 71% (63%-80%) and 107% (96%-120%), respectively. Mean cortisol effects (Day 42/Day 1 ratio) were generally similar for MF/F 400μg/10μg and FP/S 460μg/42μg (GMR 119%; 90%CI 101%-140%). Effects of MF/F 200μg/10μg on cortisol AUC were similar to placebo (GMR 92%; 90%CI 78%-110%), whereas MF/F 400μg/10μg and FP/S 460μg/42μg lowered cortisol AUC versus placebo (GMR 78%; 90%CI 66%-92% and GMR 66%; 90%CI 56%-78%, respectively). Oral inhalations of MF/F MDI were generally safe and well tolerated.
CONCLUSIONS: MF/F 400μg/10μg or FP/S 460μg/42μg administered BID via MDI for 42 days led to similar reductions from baseline in mean cortisol AUC (22% and 34% lower than placebo, respectively), whereas the effect of MF/F 200μg/10μg on plasma cortisol levels was similar to placebo.
CLINICAL IMPLICATIONS: Low dose MF/F MDI did not appear to have detectable effects on cortisol whereas high dose MF/F or FP/S MDI appeared to lower cortisol levels in some individuals.
DISCLOSURE: Teddy Kosoglou: Employee: Merck Sharp Dohme
James Hubbell: Employee: Merck Sharp & Dohme Corp
Fengjuan Xuan: Employee: Merck Sharp & Dohme Corp.
David Cutler: Employee: Merck Sharp & Dohme Corp
Amy Johnson-Levonas: Employee: Merck Sharp & Dohme Corp
Danlin Xu: Employee: Merck Sharp & Dohme Corp
Bhavna Kantesaria: Employee: Merck Sharp & Dohme Corp
Kenneth Kim: Consultant fee, speaker bureau, advisory committee, etc.: Merck Sharp & Dohme Corp
S. David Miller: Consultant fee, speaker bureau, advisory committee, etc.: Merck Sharp & Dohme Corp
No Product/Research Disclosure InformationMerck Sharp & Dohme Corp., Whitehouse Station, NJ