Chest
Volume 128, Issue 1, July 2005, Pages 70-77
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Clinical Investigations
Asthma
Effects of Mometasone Furoate Dry Powder Inhaler and Beclomethasone Dipropionate Hydrofluoroalkane and Chlorofluorocarbon on the Hypothalamic-Pituitary-Adrenal Axis in Asthmatic Subjects

https://doi.org/10.1378/chest.128.1.70Get rights and content

Study objectives

Mometasone furoate dry powder inhaler (MF-DPI) [400 μg] is an inhaled corticosteroid (ICS) that is effective in the treatment of asthma. MF-DPI has a low potential for suppression of the hypothalamic-pituitary-adrenal (HPA) axis at its clinical dose. The effect of MF-DPI, 400 μg qd, on the HPA axis was compared to that of beclomethasone dipropionate (BDP) using hydrofluoroalkane (HFA) and chlorofluorocarbon (CFC) propellants via metered-dose inhalers (MDIs) twice daily.

Design and interventions

This randomized, third-party blind, parallel-group study compared the effects of MF-DPI 400 μg one puff qd in the morning (n = 18), HFA-BDP 200 μg two puffs MDI bid (n = 18), and CFC-BDP 400 μg two puffs MDI bid (n = 17) for 14 days on the area under the 24-h serum cortisol concentrations curve (AUC0–24) and on total 24-h urinary free cortisol excretion in mild asthmatic subjects. Effects on morning/evening peak expiratory flow (PEF) and on inhaled albuterol use were also assessed. Adverse events that occurred during or ≥ 30 days after the study were recorded.

Results

The mean decrease from baseline in the serum cortisol concentrations AUC0–24 in the MF-DPI group was significantly less than in either the HFA-BDP (p = 0.024) or the CFC-BDP (p = 0.011) groups. Decreases in serum cortisol concentrations AUC0–24 in the two BDP groups did not differ from one another. The MF-DPI group trended toward higher morning and evening PEF than either BDP group. Treatment-associated adverse events were reported by seven subjects in the MF-DPI group, vs one subject in the HFA-BDP and three subjects in the CFC-BDP groups; these were mild, and no subject discontinued treatment due to an adverse event.

Conclusions

Fourteen days of treatment with MF-DPI 400 μg qd was associated with a significantly lesser decrease in the serum cortisol concentrations AUC0–24 compared with HFA-BDP 200 μg MDI or CFC-BDP 400 μg MDI bid.

Section snippets

Subjects

Male and female subjects with mild asthma 18 to 65 years old were eligible for the study. All subjects had a history of asthma for ≥ 6 months and a FEV1 of ≥ 80% predicted at screening after withholding short- and long-acting β2-receptor agonist treatment for 6 h and 48 h, respectively. At screening or within the previous 12 months, subjects had to demonstrate reversibility of airflow obstruction, defined as a ≥ 12% (or ≥ 200 mL absolute volume) increase in FEV1 after albuterol administration.

Demographics

A total of 53 subjects were enrolled and randomized to receive MF-DPI (n = 18), HFA-BDP (n = 18), or CFC-BDP (n = 17). Four subjects were discontinued from the study due to protocol ineligibility (MF-DPI, n = 1; HFA-BDP, n = 1; CFC-BDP, n = 2). Five subjects were excluded from the per protocol population; one subject in the MF-DPI group had a low serum cortisol at screening, while three subjects were excluded for using oral contraceptives (HFA-BDP, n = 1; CFC-BDP, n = 2) and one subject was

Discussion

This study compared the effect of MF-DPI on the HPA axis with that of another commonly used ICS, BDP, in subjects with asthma. The results demonstrate that a similar magnitude of HPA-axis suppression occurred with BDP via HFA and CFC MDI, despite the differences in BDP doses: 200 μg bid vs 400 μg bid. This confirms previous findings by Jackson and Lipworth1314 indicating greater systemic bioavailability and enhanced cortisol suppression with the HFA formulation of BDP vs the CFC formulation.

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    This study supported by Integrated Therapeutics Group, Inc., a subsidiary of Schering-Plough Corporation, Kenilworth, NJ.

    This study was performed at Simbec Research Ltd, Merthyr Tydfil, Cardiff, UK.

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