Asthma is recognized as an inflammatory disease with accompanying bronchospasm. With that knowledge, pharmacotherapy for asthma has evolved into controlled and reliever therapies. For the past twenty years, inhaled corticosteroids have evolved as the mainstay of anti- inflammatory controller therapy based primarily on the notion of increased safety compared to systemic corticosteroids. With the development of increasingly potent steroid molecules with different bio- availability profiles, considerable controversy has arisen regarding the relative safety and efficacy of the commercially available inhaled corticosteroid preparations. This study is designed to determine the relative therapeutic ratios (efficacy/safety) and establish the pharmacokinetics and pharmacodynamics of triamcinolone acetonide, fluticasone propionate and budesonide. It is a randomized,single-blind (investigator-blind), parallel, comparative study of 96 stable asthma patients (32 patients per treatment group) at one study site. Male and female patients, ages 18 to 60 years with at least a two year history of mild to moderate persistent asthma, will receive one of three dose levels (1 puff bid x 3 weeks, 2 puffs bid x 3 weeks, and 3 puffs bid x 3 weeks) of Azmacort (trimcinolone acetonide) HFA 225 mcg/puff, Flovent (fluticasone) 220 mcg/puff, and Pulmicort Turbuhaler (budesonide) 200 mcg/puff, in randomized sequence after a 10-14 day run-in period with 7-10 days washout between each of the three treatment periods. Patients will be evaluated for relative efficacy by methacholine PD20, FEV1, PEFR, beta-2 use, nighttime awakenings, asthma symptom scores; and for relative safety by 24-hour serum and urinary cortisol/creatinine profiles and serum cortisol AUC (0-24) ACTH stimulation test. Changes from baseline will be assessed at the end of each treatment with PD20 and 24 hour AUC plasma cortisol and urinary cortisol/creatinine. The primary comparisons will be made between treatments using an analysis of variance (ANOVA) model with factors: treatment, dose, period, sequence, and subject nested in (sequence x dose).
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