Tolerability of a Salmeterol Xinafoate/Fluticasone Propionate Hydrofluoroalkane Metered-Dose Inhaler in Adolescent and Adult Patients with Persistent Asthma: A 52-Week, Open-Label, Stratified, Parallel-Group, Multicenter Study
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BACKGROUND: Many patients with asthma require an inhaled long-acting beta(2)-agonist (LABA) in addition to an inhaled corticosteroid to adequately control their disease. OBJECTIVE: The purpose of this study was to assess the long-term tolerability of a salmeterol xinafoate/ fluticasone propionate (SFC) hydrofluoroalkane metered-dose inhaler (MDI) at 3 different doses BID. METHODS: This 52-week, open-label, stratified, parallel-group study assessed SFC in patients with persistent asthma. Patients, aged > or = 12 years, with a diagnosis of asthma for > or = 6 months, and a percent predicted forced expiratory volume in 1 second (FEV(1)) or peak expiratory flow (PEF) between 40% and 90% were enrolled between January 1999 and June 1999. The last patient completed the 12-month study in June 2000. Patients were allowed to continue their current asthma treatment during run-in, with the exception that short-acting beta(2)-agonists (SABAs), LABAs, and oral bronchodilators were not to be used 6, 12, and 24 hours, respectively, prior to the randomization visit. During the open-label randomized treatment period, patients were instructed to discontinue all other asthma medications with the exception of the albuterol MDI to use on an as-needed basis. Patients were assigned to treatment based on their existing asthma regimen: SABA monotherapy or LABA with or without fluticasone propionate (FP) <250 microg/d or equivalent (group 1); FP 250 to 500 microg/d or equivalent with or without LABA (group 2); and FP >500 to 1000 microg/d or equivalent with or without LABA (group 3). Patients administered 2 inhalations BID of SFC hydrofluoroalkane at doses of 25/50 microg/actuation (group 1), 25/125 microg/actuation (group 2), or 25/250 pg/actuation (group 3). The primary end point was tolerability as assessed by adverse events (AEs). AEs were determined via diary cards and investigator inquiry at visits. Serious AEs were defined as death, any life-threatening event, hospitalization, disability, congenital anomaly in the patient's offspring, or other important medical events judged by the investigator to be serious. Other outcomes included clinical laboratory tests (hematology, chemistry, electrolytes), 24-hour urinary-free cortisol excretion, 12-lead electrocardiograms, oropharyngeal examinations, vital signs, clinic visit lung function tests (FEV(1) and PEF), daily diary card entries of morning PEF, and rescue medication usage. RESULTS: Of the 372 patients assessed for eligibility, 325 from 22 centers across Canada were enrolled and randomized to treatment. Group 1 consisted of 98 patients (55% women; 86% white; mean age, 37 years; mean [SD] weight, 79  kg). Group 2 consisted of 109 patients (46% women; 94% white; mean age, 44 years; mean [SD] weight, 80  kg). Group 3 consisted of 118 patients (47% women; 90% white; mean age, 45 years; mean [SD] weight, 80  kg). A total of 15 adolescents (aged 12-17 years) comprised 11%, 2%, and 2% of groups 1, 2, and 3, respectively. Treatments were well tolerated, and 274 (84%) of the 325 patients enrolled completed the study. Upper respiratory tract infection was the most common AE reported: 52%, 37%, and 49% of patients in groups 1, 2, and 3, respectively. Twenty (6%) patients withdrew because of an AE, with worsening asthma being the most frequent reason (n = 9). None of the serious AEs (11 [3 %]) were considered drug related by the investigators. Improvements in FEV(1) and PEF and re- duction in symptomatic albuterol use occurred during the first 4 weeks and were maintained in all groups throughout the 52-week study. CONCLUSIONS: BID doses of SFC hydrofluoroalkane 50/100 pg, 50/250 pg, and 50/500 pg administered via MDI for 52 weeks were well tolerated in this population of adolescents and adults with persistent asthma.