A 12-week, multicenter, randomized, partially blinded, active-controlled, parallel-group study of budesonide inhalation suspension in adolescents and adults with moderate to severe persistent asthma previously receiving inhaled corticosteroids with a metered-dose or dry powder inhaler.
BACKGROUND
Nebulized budesonide inhalation suspension (BIS) is approved in the United States for children with asthma aged 1 to 8 years.


OBJECTIVE
The primary objective of this study was to compare the efficacy of BIS 0.5 mg QD and 2.0 mg BID in terms of the mean change from baseline to end of treatment in predose forced expiratory volume in 1 second (FEV1).


METHODS
In this 12-week, partially blinded, randomized study, subjects aged >or=12 years with moderate to severe persistent asthma previously receiving inhaled corticosteroids (ICSs) by dry powder inhaler (DPI) or metered-dose inhaler (MDI) continued therapy during a 2- to 3-week run-in period and then switched to BIS 0.5 mg QD, 1.0 mg QD, 1.0 mg BID, or 2.0 mg BID, or budesonide DPI 400 microg BID (active reference arm). Besides FEV1 (the primary variable), other outcome variables included changes in forced vital capacity (FVC) from baseline to weeks 4, 8, and 12 and to the average over the treatment period; as well as changes from baseline to the end of treatment in diary-collected daytime and nighttime asthma symptom scores, rescue medication use, nighttime awakenings due to asthma, morning and evening peak expiratory flow (PEF), percentages of symptom-free and medication-free periods, and the incidence of predefined asthma events. Adverse events were recorded by subjects. Steady-state pharmacokinetics of budesonide were assessed in all treatment arms. Efficacy analyses included data in a modified intent-to-treat approach. Differences in the change from baseline to end of treatment in FEV1 were assessed using analysis of covariance (ANCOVA). For secondary variables, changes from baseline to each visit or to the treatmentperiod average were compared among groups using an ANCOVA model. P <or= 0.05 was considered statistically significant.


RESULTS
The randomized population consisted of 758 subjects: 57 (7.5%) aged 12 to <17 years, 667 (88.0%) aged 17 to <65 years, and 34 (4.5%) aged >or=65 years. There was no significant difference in mean change in predose FEV1 between BIS 0.5 mg QD and BIS 2.0 mg BID (0.02 vs 0.01 L). On average, mean values for the BIS dosage groups did not indicate any deterioration from baseline to the treatment period for variables associated with asthma control such as FEV1, FVC, daytime and nighttime asthma symptom scores, rescue medication use, nighttime awakenings, morning and evening PEF, percentages of symptom-free and rescue medication-free periods, and predefined asthma events. The BIS 1.0-mg BID treatment appeared to be closest to budesonide DPI in plasma budesonide concentrations and improvement in predose FEV1 (0.08 vs 0.12 L). All treatments were well tolerated.


CONCLUSIONS
In this study, no difference in efficacy between BIS 2.0 mg BID and 0.5 mg QD was found in adolescents and adults with persistent asthma when transitioned from ICSs delivered with a DPI or MDI. Subjects taking all BIS dosages experienced similar responses for variables associated with asthma control.
Murphy
Kevin
K
Midwest Children's Chest Physicians, Omaha, Nebraska 68114, USA. murphknsc@aol.com
Noonan
Michael
M
Silkoff
Philip E
PE
Uryniak
Thomas
T
D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019819:Budesonide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011208:Powders; D012720:Severity of Illness Index; D012737:Sex Factors; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D011208:Powders; D019819:Budesonide