A comparison of 2 extrafine hydrofluoroalkane-134a-beclomethasone formulations on methacholine hyperresponsiveness.
BACKGROUND
Small airways inflammation is a recognized pathologic component of asthma, and it is postulated that the observed airway-wall remodeling in small airways could be due to uncontrolled inflammation in airways that are not penetrated by conventional inhaled corticosteroids. Thus, extrafine particle formulations of inhaled corticosteroids are of clinical interest.


OBJECTIVE
To compare 2 extrafine solution hydrofluoroalkane-134a formulations of beclomethasone dipropionate (Beclate and Qvar).


METHODS
Fifteen asthmatic patients (mean +/- SEM forced expiratory volume in 1 second [FEV1], 2.62 +/- 0.21 L; provocative concentration of methacholine causing a 20% decrease in FEV1 [PC20], 1.06 +/- 0.58) were randomized to completion in a placebo-controlled, double-blind, crossover manner to receive Beclate or Qvar at doses of 100 or 400 microg/d for 2 weeks, with a 1-week washout period before each randomized treatment. Methacholine hyperresponsiveness was the primary outcome measure.


RESULTS
The 2 formulations were equivalent in terms of predefined equivalence limits of +/- 1 doubling dilution for PC20 at both doses: -0.25 (95% confidence interval [CI], -0.77 to 0.27) doubling dilution difference between the 100-microg doses and a 0.26 (95% CI, -0.29 to 0.82) doubling dilution difference between the 400-microg doses for the difference between Beclate and Qvar, respectively. Both formulations, at either dose, produced a statistically significant (P < .05) reduction in mean exhaled nitric oxide levels: 400 microg/d of Beclate, 14.1 ppb (95% CI, 5.6 to 22.6 ppb); and 400 microg/d of Qvar, 14.2 ppb (95% CI, 6.0 to 22.4 ppb). The higher doses produced a statistically significant (P < .05) reduction in early morning urinary cortisol-creatinine ratio (geometric mean fold suppression: Beclate, 1.48 [95% CI, 1.16 to 1.89]; and Qvar, 1.42 [95% CI, 1.12 to 1.79]). Both formulations significantly improved peak expiratory flow, FEV1, and forced expiratory flow between 25% and 75% of forced vital capacity at the higher doses (P < .05).


CONCLUSIONS
Beclate and Qvar were equivalent for all primary and secondary outcome measures.
Fardon
Tom C
TC
Asthma and Allergy Research Group, Division of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland. tom.fardon@doctor.com
Burns
Patricia
P
Barnes
Martyn L
ML
Lipworth
Brian J
BJ
D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy; D001507:Beclomethasone / Q000008:administration & dosage* / Q000627:therapeutic use; D001980:Bronchi / Q000187:drug effects; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D003401:Creatine / Q000652:urine; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D006854:Hydrocortisone / Q000652:urine; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis; D013147:Spirometry; D013810:Therapeutic Equivalency; D016896:Treatment Outcome; D005466:Fluorocarbons
D000335:Aerosol Propellants; D018927:Anti-Asthmatic Agents; D001507:Beclomethasone; D016085:Bronchoconstrictor Agents; D003401:Creatine; D006845:Hydrocarbons, Fluorinated; D006854:Hydrocortisone; D016210:Methacholine Chloride; D009569:Nitric Oxide; C094049:apaflurane; D005466:Fluorocarbons