Efficacy and tolerability of fluticasone propionate/salmeterol administered twice daily via hydrofluoroalkane 134a metered-dose inhaler in adolescent and adult patients with persistent asthma: a randomized, double-blind, placebo-controlled, 12-week study

This study compared the efficacy andtolerability of the combination of fluticasone propionate (FP) and salmeterol (SAL) delivered via a single hydrofluoroalkane (HFA) 134a metered-dose inhaler (MDI) with those of its 2 components alone delivered via a chlorofluorocarbon (CFC) MDI and placebo (PLA) delivered via HFA MDI in adolescent and adult patients with persistent asthma that was not controlled by medium doses (equivalent to FP 440–660 μg/d) of inhaled corticosteroids (ICSs). This was a randomized, double-blind,placebo-controlled, parallel-group study consisting of a 2-week, single-blind, placebo run-in period followed by a 12-week, double-blind treatment period. Participants had to be ≥12 years of age and have a diagnosis of asthma requiring pharmacotherapy for at least 6 months before the study. Patients had to have used ICS therapy for ≥3 months before the study and at a consistent dose for the previous month. Lack of asthma control was defined as a forced expiratory volume in 1 second (FEV 1) that was 40% to 85% of the predicted value. Patients could not enter the double-blind treatment period if they had 3 days when they required >12 puffs of rescue albuterol per day or >3 nighttime awakenings due to asthma that required treatment with albuterol during the 7 days before the randomization visit. Patients were randomized to receive one of the following treatments delivered via MDI twice daily for 12 weeks: FSC 220/42 μg HFA (2 inhalations of FSC 110/21 μg; 125 μg/21 μg ex-valve); FP 220 μg CFC (2 inhalations of FP 110 μg); SAL 42 μg CFC (2 inhalations of 21 μg); or 2 inhalations of PLA HFA. The primary efficacy end point for FSC versus FP was the mean area under the 12-hour serial FEV 1 curve relative to the prerandomization baseline (FEV 1 AUC bl). The primary efficacy end points for FSC versus SAL were the mean change from baseline in morning predose FEV 1 at end point and the probability of not being withdrawn from the study due to worsening asthma. Tolerability assessments included electrocardiograms, routine clinical laboratory tests, vital signs, oropharyngeal examinations, and physical examinations. Adverse events were assessed at each clinic visit. Thirty-two adolescent and 333 adult patientswere randomly assigned to receive double-blind treatment. The treatment groups were comparable at baseline with respect to demographic characteristics (mean age, 38–41 years; white race, 78%–88%) and pulmonary function (mean percent predicted FEV 1, 68%–6