A systemic bioactivity comparison of double-strength and regular-strength beclomethasone dipropionate MDI formulations

Background: The efficacy and safety of regular-strength beclomethasone dipropionate MDI prescribed within its recommended dosing range of 2 to 5 puffs three to four times daily has been well established in more than 25 years of worldwide use. A more concentrated formulation delivering 84 mu g per puff was developed to provide for a more convenient twice-daily dosing regimen. Objective: This randomized, single-blinded, positive and placebo-controlled, parallel-group, multiple-dose bioactivity study was conducted to assess the potential of a new beclomethasone dipropionate 84 mu g double-strength metered-dose inhaler (Vanceril 84 mu g Double Strength Inhalation Aerosol/Key) to cause hypothalamic-pituitary-adrenocortical axis suppression. Methods: Beclomethasone dipropionate double-strength 84 mu g was compared with beclomethasone dipropionate regular-strength 42 mu g, orally administered prednisone, and placebo inhaler after 36 consecutive days of administration in adults with moderate asthma. Beclomethasone dipropionate double-strength was administered as 5 puffs BID and beclomethasone dipropionate regular-strength was administered as 10 puffs BID for the same total daily dose of 840 mu g of beclomethasone dipropionate. Oral prednisone was administered by mouth at 10 mg once a day. The potential for hypothalamic-pituitary-adrenocortical axis suppression was evaluated by an adrenocorticotropic hormone (ACTH) stimulation test using cosyntropin 250 mu g in 500 mL normal saline infused over six hours on the 36th day of treatment. Sixty-four patients completed this study. Results: No clinically significant post-study findings were observed from physical examination, electrocardiogram, or clinical laboratory evaluation for any treatment group. No serious or unexpected adverse events were reported. On the 36th day of treatment, there was a significant (P < .01) difference in the plasma cortisol concentration response to cosyntropin stimulation between the prednisone and placebo treatment groups at the sixth hour of infusion. There was no significant difference in the plasma cortisol concentration response to cosyntropin stimulation between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength treatment groups and the placebo group. In addition, comparison of the response between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength groups showed no significant difference. Conclusion: Beclomethasone dipropionate, administered either via a double-strength (84 mu g/puff) or regular-strength (42 mu g/puff) inhaler dosed at 840 mu g/day showed no evidence of hypothalamic-pituitary-adrenocortical axis suppression in adults with moderate asthma.