Aim and Methods: We conducted two studies in healthy male subjects to assess the effect on serum cortisol
levels of the novel inhaled corticosteroid GW870086, dosed at 6 mg, 12 mg and 15 mg/day (dry powder inhaler;
NCT00549497) for 3 days and 5 mg and 8.75 mg/day (nebules; NCT01160003) for 14 days.
Results: In the 3-Day Study, the greatest suppression of serum cortisol weighted mean (0-24 hour) of GW870086,
compared with placebo, was observed on Day 1 (29% suppression at the 15 mg dose). In the 14-Day Study, the greatest
suppression was 15% for GW870086 5 mg. None of these values was considered clinically significant. After 3 days’
dosing, GW870086 was absorbed slowly (tmax: 0.8-3.5 hours) and eliminated with a t1/2 of 22.7 hours; the highest systemic
exposure (AUC) was 26.7 ng.hour/mL. After 14 days, GW870086 tmax was 0.3-0.4 hours and t1/2 25.0-29.6 hours; the
highest AUC was 16.7 ng.hour/mL. No safety issues were identified in these studies.
Conclusion: At estimated therapeutic and supratherapeutic doses, which achieved high exposure (AUC) in both studies,
GW870086 did not exhibit the usual level of hypothalamic-pituitary-adrenal axis suppression that would be expected with
traditional inhaled corticosteroids.