Flovent Diskus - Clinical Pharmacology

In clinical trials with fluticasone propionate inhalation powder using doses up to and including 250 mcg twice daily, occasional abnormal short cosyntropin tests (peak serum cortisol <18 mcg/dL) were noted both in patients receiving fluticasone propionate and in patients receiving placebo. The incidence of abnormal tests at 500 mcg twice daily was greater than placebo. In a 2-year study carried out with the DISKHALER ® inhalation device in 64 patients with mild, persistent asthma (mean FEV1 91% of predicted) randomized to fluticasone propionate 500 mcg twice daily or placebo, no patient receiving fluticasone propionate had an abnormal response to 6-hour cosyntropin infusion (peak serum cortisol < 18 mcg/dL). With a peak cortisol threshold < 35 mcg/dL, one patient receiving fluticasone propionate (4%) had an abnormal response at 1 year; repeat testing at 18 months and 2 years was normal.

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Another patient receiving fluticasone propionate (5%) had an abnormal response at 2 years. No patient on placebo had an abnormal response at 1 or 2 years. In a placebo-controlled clinical study conducted in patients 4 to 11 years of age, a 30-minute cosyntropin stimulation test was performed in 41 patients after 12 weeks of dosing with 50 or 100 mcg twice daily of fluticasone propionate via the DISKUS device.

One patient receiving FLOVENT DISKUS 50 mcg (fluticasone propionate inhalation powder, 50 mcg) FLOVENT DISKUS 100 mcg (fluticasone propionate inhalation powder, 100 mcg) FLOVENT DISKUS 250 mcg (fluticasone propionate inhalation powder, 250 mcg) 5 fluticasone propionate via DISKUS had a prestimulation plasma cortisol concentration < 5 mcg/dL, and 2 patients had a rise in cortisol of < 7 mcg/dL. However, all poststimulation values were >18 mcg/dL.

Clinical Trials:

Four double-blind, parallel, placebo-controlled, US clinical trials were conducted in 1036 adolescent and adult patients ( 12 years of age) with asthma to assess the efficacy and safety of FLOVENT DISKUS. These studies included fixed doses of 100, 250, and 500 mcg twice daily compared to placebo to provide information about appropriate dosing to cover a range of asthma severity. Patients with asthma included in these studies were those not adequately controlled with bronchodilators alone, and those already maintained on daily inhaled corticosteroids. All doses were delivered by inhalation of the contents of 1 or 2 blisters from the DISKUS twice daily. Displayed in the figures below are results of pulmonary function tests (mean percent change from baseline in FEV1 prior to AM dose) for 3 recommended dosages of fluticasone propionate inhalation powder (100, 250, and 500 mcg twice daily) and placebo from the four 12-week trials in adolescents and adults. Because these trials used predetermined criteria for lack of efficacy, which caused more patients in the placebo group to be withdrawn, pulmonary function results at Endpoint, which is the last evaluable FEV1 result and includes most patients’ lung function data, are also provided.