846 The Novel Inhaled Corticosteroid Ciclesonide Is Efficaciousand Has a Favorable Safety Profile in Adults and AdolescentsWith Severe Persistent Asthma

W. Busse1, M. Kaliner2, D. Bernstein3, A. Nayak4, S. Kundu5, J.Williams5, J. Fish5, D. Banerji5; 1University of Wisconsin, Madison, WI,2Institute for Asthma and Allergy, Washington, DC, 3Bernstein ClinicalResearch Center, Cincinnati, OH, 4Sneeze, Wheeze and Itch Associates,Normal, IL, 5Aventis Pharmaceuticals, Bridgewater, NJ.RATIONALE: In patients with severe persistent asthma treated withhigh-dose inhaled corticosteroids (ICS), the ICS therapeutic margin ideal-ly should be wide. Ciclesonide (CIC), a novel ICS with high lung deposi-tion (~52%) and low bioavailability (<1%), may fulfill this criteria. CICis mainly converted in the lung to its active metabolite, desisobutyryl-ciclesonide, which possesses high serum protein binding.METHODS: In a multicenter, double-blind, double-dummy, parallel-group, placebo (PBO)-controlled study, the efficacy and safety of CICwere evaluated in patients with severe asthma. 531 patients (age ≥12years; FEV1 40-65% predicted) were randomized to receive CIC 160 �gbid (CIC320), CIC 320 �g bid (CIC640), fluticasone propionate (FP) viachlorofluorocarbon MDI 440 �g bid (FP880) (ex-actuator) or PBO for 12weeks. FP was included as an active comparator; to maintain blindingintegrity, FP was delivered at a 37% higher dose.RESULTS: Both CIC and FP demonstrated significant dose-relatedimprovements in FEV1 (CIC320, 0.11 L [P=0.0374]; CIC640, 0.18 L[P=0.0008]; FP880, 0.24 L [P=0.0001]) versus PBO. 24-hour asthmasymptom scores and daily albuterol use were significantly reduced for allactive treatments (P<0.0001). More patients discontinued due to lack ofefficacy with PBO than with CIC or FP (P=0.0001). Incidence of adverseevents was similar across all groups. Rates of oral candidiasis were high-er with FP880 (11.6%) than with CIC (CIC320, 1.6%; CIC640, 0%) orPBO. HPA axis function at 12 weeks was not significantly different frombaseline in any group.CONCLUSIONS: Ciclesonide and fluticasone propionate are effectivein patients with severe asthma; both CIC doses were well tolerated.Funding: Aventis and Altana Pharma

847 Ciclesonide, Administered Once Daily, Has a Low Incidenceof Oropharyngeal Adverse Events in Pediatric AsthmaPatients

E. Gelfand1, M. Boguniewicz1, S. Weinstein2, C. Bernstein3, M. Lloyd4,P. Zhang4, J. Williams4, D. Banerji4, P. Hamedani4; 1National JewishMedical & Research Center, Denver, CO, 2Allergy and Asthma Special-ists Medical Group, Huntington Beach, CA, 3Bernstein ClinicalResearch Center, Cincinnati, OH, 4Aventis Pharmaceutical Inc, Bridge-water, NJ.RATIONALE: Use of inhaled corticosteroids (ICS) is associated withlocal oropharyngeal adverse events that can negatively impact treatmentinitiation and adherence. Ciclesonide (CIC) delivered via hydrofluo-roalkane metered-dose inhaler is a new, effective ICS with low oral depo-sition (<1%) and high lung deposition (~52%). CIC is primarily convert-ed in the lung to its active metabolite, desisobutyryl-ciclesonide (des-CIC). Des-CIC has high serum protein binding and high glucocorticoidreceptor affinity. Importantly, des-CIC forms lipid conjugates in lung tis-sue, increasing lung residence time, thereby supporting the rationale foronce-daily (qd) dosing in pediatric asthmatics.METHODS: Two identical, multicenter, multinational, double-blind,placebo (PBO)-controlled, parallel-group, clinical trials were conductedto evaluate the effect of CIC on local adverse events. A total of 1031 pedi-atric patients with mild-to-severe persistent asthma were randomized toreceive CIC 40, 80 or 160 �g, or PBO qd for 12 weeks. All patients under-went oropharyngeal examination at every study visit (weeks 1, 2, 4, 8 and12) to test for oral candidiasis, and suspected oral fungal infections wereverified by culture. An integrated analysis is presented.

RESULTS: Within the safety population (n=1025), only three cases(0.4%) of oral candidiasis were reported; all incidences occurred in theCIC groups (CIC80, n=1; CIC160, n=2). The incidence of pharyngitis wassimilar across all CIC groups, and only one case of hoarseness (0.1%) wasreported in the CIC treatment group.CONCLUSIONS: In pediatric asthmatics, ciclesonide 40, 80 or 160 �gonce daily is associated with a low incidence of local oropharyngealadverse events compared with placebo.Funding: Aventis and Altana Pharma

848 Improved Compliance With Fluticasone Propionate and Sal-meterol (FS) in a Single Inhaler

R. D. O’Connor1, A. S. Gilmore2, R. H. Stanford3, R. Manjunath3, A. P.Legorreta4, P. M. Jhingran3; 1University of California at San Diego, SanDiego, CA, 2Health Benchmarks, Inc., Woodland Hills, CA, 3Glaxo-SmithKline, Rtp, NC, 4California Department of Health Services, Schoolof Public Health, University of California, Los Angeles, CA.RATIONALE: Previous studies have demonstrated that inhaled corticos-teroids (ICS) taken regularly (i.e., > 3 refills per year) are associated withreduced morbidity and mortality. The purpose of this study was to assesspatient adherence with fluticasone propionate/salmeterol (FS) from a sin-gle inhaler in patients with persistent asthma.METHODS: Prospective observational 12-month asthma study conduct-ed with 224 physicians participating throughout the US. Patients (≥15years) with a physician-confirmed diagnosis of asthma with no other con-current respiratory disease who were prescribed FS for the treatment ofpersistent asthma were included. Patients prescribed FS or any single con-troller agents other than ICS, prior to the start of the study, were exclud-ed. Number of FS prescription refills was determined from patient phar-macy claims and were measured over a 12-month period.RESULTS: 193 subjects were included in the analysis. The mean numberof FS refills was 4.29 (±3.36) for the 12 month follow-up. 56% of subjectshad 3 or more FS refills and 46% had 4 or more FS refills during the 12month follow-up.CONCLUSIONS: These findings suggest that FS patients on averagereceived the amount of ICS per year that has been associated with reduc-tions in morbidity and mortality in previous studies.Funding: GSK

J ALLERGY CLIN IMMUNOL Abstracts S213VOLUME 115, NUMBER 2

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849 Which Is More Effective, Inhaling Aerosol Through Nose orThrough Mouth?

A. Hashimoto, M. Nishikawa, N. Kuroda, M. Nambu; Tenri Hospital,Nara, JAPAN.RATIONALE: Since the optimal method of inhalation is not established, wecompared the inhalation efficiencies following some inhalation conditions.METHODS: In inhalation therapy with a nebulizer, some asthmatic chil-dren inhale aerosol through nose, and some do through mouth. Someinhale it with effort ventilation, and some do with resting ventilation. Uri-nary excretion of disodium cromoglycate (DSCG) has been reported as auseful indicator of inhalation efficiency. Therefore, three healthy volun-teers inhaled 20mg of DSCG (1)through nose with effort ventilation,(2)through nose with resting ventilation, (3)through mouth with effortventilation, or (4)through mouth with resting ventilation, via a nebulizerwith a face mask. Urine samples from them were collected more than 4hours after inhalation administration. Urinary concentrations of DSCGwere measured by high-performance liquid chromatography.RESULTS: Each amount (microgram) of urinary excretion of DSCG insubject A was 851,381,850,and 428 in order of (1)-(4)(shown above); insubject B was 959,447,348 and 259; in subject C was 447,769,1540,and 1015.CONCLUSIONS: ‘Which is more effective, inhaling aerosol throughnose or through mouth’ depends on individuals. In most cases in thisstudy, inhalation efficiency is higher when aerosol was inhaled with effortventilation than with resting ventilation.

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