Efficacy and safety of budesonide administered by pressurized metered-dose inhaler in children with asthma.

BACKGROUND: Budesonide is approved for delivery using a nebulized solution and dry-powder inhaler, but its use through a pressurized metered-dose inhaler (pMDI) in pediatric patients with asthma has not been determined. OBJECTIVE: To examine the efficacy and safety of 160 µg twice daily of budesonide through a pMDI vs placebo in children 6 to younger than 12 years with asthma and a demonstrated need for inhaled corticosteroids. METHODS: A 6-week, international, multicenter, double-blinded, parallel-group, phase 2 study randomized 304 pediatric patients (mean age, 9 years; 21.7% <8 years) 1:1 to 160 µg (80 µg × 2 inhalations) twice daily of budesonide through a pMDI or placebo after a 7- to 21-day run-in period. The primary efficacy end point was change from baseline in morning peak expiratory flow (PEF); safety end points included adverse events, vital signs, and discontinuations. RESULTS: Budesonide treatment significantly improved morning PEF vs placebo; mean treatment effect (budesonide vs placebo) was 13.6 L/min (P < .0001). Budesonide also showed significant improvements vs placebo for forced expiratory volume in 1 second, evening PEF, forced expiratory flow at 25% to 75% of pulmonary volume, reliever medication use, nighttime awakenings, awakenings with reliever use, and percentage of patients with at least 15- and at least 30-L/min increase in morning PEF from baseline. The numbers of patients experiencing adverse events and discontinuations were smaller in the budesonide than in the placebo group. No serious adverse events were reported. CONCLUSION: Budesonide at 160 µg twice daily through a pMDI was generally well tolerated and significantly improved lung function, symptoms, rescue medication use, and nighttime awakenings vs placebo in children 6 to younger than 12 years with asthma and a demonstrated need for inhaled corticosteroids.

Therapeutic equivalence of budesonide/formoterol delivered via breath-actuated inhaler vs pMDI.

RATIONALE: To assess equivalence of twice daily (bid) budesonide/formoterol (BUD/FM) 160/4.5 µg via breath-actuated metered-dose inhaler (BAI) versus pressurized metered-dose inhaler (pMDI). METHODS: This 12-week, double-blind, multicenter, parallel-group study, randomized adolescents and adults (aged ≥12 years) with asthma (and ≥3 months daily use of inhaled corticosteroids) to BUD/FM BAI 2 × 160/4.5 µg bid, BUD/FM pMDI 2 × 160/4.5 µg bid, or BUD pMDI 2 × 160 µg bid. Inclusion required prebronchodilator forced expiratory volume in one second (FEV1) ≥45 to ≤85% predicted, and reversibility of ≥12% in FEV1 (ages 12 to <18 years) or ≥12% and 200 mL (ages ≥18 years). Confirmation that 60-min postdose FEV1 response to BUD/FM pMDI was superior to BUD pMDI was required before equivalence testing. Therapeutic equivalence was shown by treatment effect ratio of BUD/FM BAI vs BUD/FM pMDI on 60-min postdose FEV1 and predose FEV1 within confidence intervals (CIs) of 80-125%. RESULTS: Mean age of 214 randomized patients was 42.7 years. BUD/FM pMDI was superior to BUD pMDI (60-min postdose FEV1 treatment effect ratio, 1.10; 95% CI, 1.06-1.14; p < 0.001). Treatment effect ratios for BUD/FM BAI versus pMDI for 60-min postdose FEV1 (1.01; 95% CI, 0.97-1.05) and predose FEV1 (1.03; 95% CI, 0.99-1.08) were within predetermined CIs for therapeutic equivalence. Adverse event profiles, tolerability, and patient-reported ease of use were similar. CONCLUSIONS: BUD/FM 2 × 160/4.5 µg bid BAI is therapeutically equivalent to BUD/FM conventional pMDI. The introduction of BUD/FM BAI would expand options for delivering inhaled corticosteroid/long-acting ß2-agonist combination therapy to patients with moderate-to-severe asthma. ClinicalTrials.gov NCT01360021.

Bronchodilator effect of single-dose formoterol administered by pressurized metered-dose inhaler in children with asthma aged 6 to <12 years receiving budesonide.

Dose-response of formoterol via pressurized metered-dose inhaler (pMDI) has not been determined in asthmatic pediatric patients aged 6 to <12 years. This study was designed to assess the bronchodilating dose-response of three formoterol pMDI doses in children with stable asthma aged 6 to <12 years receiving twice-daily (b.i.d.) budesonide 160 micrograms. A U.S., multicenter, five-way crossover study compared single doses of formoterol, a long-acting beta-agonist, via pMDI (2.25, 4.5, and 9 micrograms) or dry powder inhaler (12 micrograms; active comparator) and placebo, with a 3- to 14-day washout period between doses. Budesonide pMDI 160 micrograms, an inhaled corticosteroid, was given b.i.d. throughout the study. Fifty-four pediatric patients (mean age, 9.2 years; mean asthma history, 6.1 years) were randomized. All formoterol doses showed significantly higher average 12-hour forced expiratory volume in 1 second (FEV1; area under the curve) versus placebo (primary efficacy). Formoterol pMDI 4.5 and 9 micrograms showed significantly greater average 12-hour FEV1 than formoterol 2.25 micrograms (p = 0.0007 and p = 0.0001, respectively). Formoterol also resulted in significant improvement in maximum FEV1 during the 12-hour treatment period (secondary efficacy) with formoterol 4.5-, 9-, and 12-microgram doses versus placebo and the formoterol 2.25-microgram dose. Bronchodilation was not maintained during the 12-hour dosing interval with formoterol 2.25 micrograms. No serious adverse events were reported. Formoterol pMDI showed generally dose-proportional pharmacokinetics to 9 micrograms, as determined by urinary excretion. Single doses of formoterol pMDI showed a dose-response, with formoterol 9 micrograms exhibiting a maximum response, in pediatric patients aged 6 to <12 years with persistent stable asthma maintained on b.i.d. budesonide pMDI 160 micrograms. Clinical trial NCT01136655, www.clinicaltrials.gov.

Budesonide inhalation suspension versus montelukast in children aged 2 to 4 years with mild persistent asthma.

BACKGROUND: Budesonide inhalation suspension (BIS) and montelukast provide acceptable asthma control, whereas overall measures favored BIS in children aged 2 to 8 years with mild persistent asthma. OBJECTIVE: We compared BIS and montelukast over a 1-year period in children aged 2 to 4 years with asthma. METHODS: Data were derived from a 52-week, open-label, randomized, active-controlled, multicenter study (NCT00641472). Children with mild asthma received either BIS 0.5 mg or montelukast 4 to 5 mg once daily. Patients were stepped up to twice-daily BIS or oral corticosteroids for mild or severe asthma worsening, respectively. Primary efficacy assessment was time to first additional asthma medication for exacerbation over 52 weeks. RESULTS: Two hundred two patients, age 2 to 4 years, received BIS (n = 105) or montelukast (n = 97). No difference was observed between the BIS and montelukast groups in median time to first additional asthma medication over 52 weeks (183 vs 86 days). Statistically significant differences were observed in favor of BIS over montelukast in the percentage of patients requiring oral steroids at 52 weeks (21.9% vs 37.1%; P = .022), the rate (number/patient/year) of additional courses of medication (1.35 vs 2.30; P = .003), the rate of additional oral steroid therapy (0.44 vs 0.88; P = .008), and caregivers' ability to manage the patient's symptoms (P = .026). Both treatments were well tolerated. CONCLUSION: BIS and montelukast provided acceptable asthma control in children aged 2 to 4 years with mild persistent asthma with no significant difference between treatments in the primary end point; however, several secondary outcomes showed statistically significant differences (and many had numerical differences) in favor of BIS over montelukast.

Long-term safety and asthma control measures with a budesonide/formoterol pressurized metered-dose inhaler in African American asthmatic patients: a randomized controlled trial.

BACKGROUND: Information surrounding the long-term safety of combination inhaled corticosteroid/long-acting ß(2)-adrenergic agonist medications in African American asthmatic patients is limited. OBJECTIVE: We sought to assess safety and asthma control with a budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide over 1 year in African American patients. METHODS: This 52-week, randomized, double-blind, parallel-group, multicenter, phase 3B safety study (NCT00419952) was conducted in 742 self-reported African American patients 12 years or older with moderate-to-severe asthma previously receiving medium- to high-dose inhaled corticosteroids. After 2 weeks using a 320 µg twice-daily budesonide pMDI, patients were randomized 1:1 to 320/9 µg twice-daily budesonide/formoterol pMDI or 320 µg twice-daily budesonide pMDI. RESULTS: Both treatments were well tolerated. Asthma exacerbation incidence and rate (per patient-treatment year) were lower with budesonide/formoterol versus budesonide (incidence, 7.7% vs 14.0% [P= .006]; rate ratio, 0.615 [P= .002]). Time to first asthma exacerbation was longer (P= .018) with budesonide/formoterol versus budesonide. The most common adverse events, regardless of study drug relationship, were headache (9.5% and 7.7%), nasopharyngitis (6.9% and 8.0%), sinusitis (4.0% and 6.3%), and viral upper respiratory tract infection (5.8% and 4.4%) for budesonide/formoterol and budesonide, respectively. Serious adverse events occurred in 12 and 15 patients, respectively; none were considered drug related. No substantial or unexpected patterns of abnormalities were observed in laboratory, electrocardiographic, or Holter monitoring assessments. Hospitalization caused by asthma exacerbation occurred in 0 and 4 patients in the budesonide/formoterol and budesonide groups, respectively. Pulmonary function and asthma control measures generally favored budesonide/formoterol. CONCLUSIONS: In this population budesonide/formoterol pMDI was well tolerated over 12 months, with a safety profile similar to that of budesonide; the asthma exacerbation rate was reduced by 38.5% versus budesonide.

The effect of budesonide/formoterol pressurized metered-dose inhaler on predefined criteria for worsening asthma in four different patient populations with asthma.

BACKGROUND: Previous studies have shown disparities between Black and Hispanic patients compared with other populations in response to asthma medications. OBJECTIVE: The aim of this analysis was to assess the effect of budesonide/formoterol pressurized metered-dose inhaler (BUD/FM pMDI) and BUD on predefined criteria for asthma worsening, an asthma control metric generally aligned with definitions of moderate asthma exacerbations, across four different populations. METHODS: Data were from four 12-week, randomized, double-blind, US studies of BUD/FM pMDI treatment in patients aged 12 years or older with varying asthma severities and of varying races. Predefined asthma events and withdrawals due to predefined events were assessed as secondary study endpoints. Study I (NCT00651651) includes data from predominantly White patients with mild to moderate asthma who were randomized to BUD/FM pMDI 160/9 µg twice daily (bid; n = 123) or BUD pMDI 160 µg bid (n = 121). Study II (NCT00652002) includes data from predominantly White patients with moderate to severe asthma who were randomized to BUD/FM pMDI 320/9 µg bid (n = 124) or BUD pMDI 320 µg bid (n = 109). Study III (NCT00702325) included self-reported Black patients with moderate to severe asthma who were randomized to BUD/FM pMDI 320/9 µg bid (n = 153) or BUD dry powder inhaler 360 µg bid (n = 148). Study IV (NCT00419757) included self-reported Hispanic patients with moderate to severe asthma who were randomized to BUD/FM pMDI 320/9 µg bid (n = 127) or BUD pMDI 320 µg bid (n = 123). Patients were to be withdrawn from the studies if they developed an asthma event, as determined by predefined criteria, except for night-time awakenings, where withdrawal was left to the study physician's judgment. RESULTS: Overall, fewer patients in the studies (study I, II, III, and IV, respectively) experienced ≥1 asthma event in the BUD/FM group (18.7%, 29.8%, 37.3%, 25.2%) versus the BUD group (21.5%, 44.0%, 45.3%, 31.7%); only study II results showed a statistically significant difference between treatments. Fewer patients with moderate to severe asthma (studies II, III, and IV) were withdrawn due to ≥1 asthma event in the BUD/FM group (10.5%, 11.8%, 3.1%, respectively) than in the BUD group (20.2%, 18.9%, 6.5%, respectively); however, percentages were similar in the BUD/FM (7.3%) and BUD (6.6%) groups in patients with mild to moderate asthma (study I). CONCLUSIONS: Predefined asthma event rates were numerically or significantly lower for patients with asthma receiving BUD/FM pMDI versus BUD, regardless of race or disease severity. Differences between the BUD/FM pMDI and BUD groups were smaller in patients with mild to moderate asthma than in those with moderate to severe asthma, most likely because patients with milder disease had lower asthma event rates. Overall, these findings support the efficacy of BUD/FM pMDI in achieving asthma control in patients with moderate to severe asthma.

Budesonide/formoterol pressurized metered-dose inhaler versus budesonide: a randomized controlled trial in black patients with asthma.

OBJECTIVE: Concerns exist that responses to long-acting ß(2)-adrenergic agonists in black patients may differ from the general population. The efficacy and safety of budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler (pMDI) versus budesonide dry powder inhaler (BUD DPI) were evaluated in adolescent and adult black asthma patients. METHODS: This 12-week, randomized, double-blind, multicenter, phase IV US study was conducted in 311 self-reported black patients aged ≥12 years with moderate to severe persistent asthma, previously receiving medium- to high-dose inhaled corticosteroid. After 2 weeks on BUD 90 µg × 2 inhalations twice daily (bid), symptomatic patients were randomized to BUD/FM 160/4.5 µg × 2 inhalations bid or BUD 180 µg × 2 inhalations bid. RESULTS: Improvement in predose forced expiratory volume in 1 second from baseline to the treatment mean (primary variable) was greater with BUD/FM versus BUD (0.16 vs. 0.07 L; p = .008); this effect was also observed at weeks 2, 6, and end of treatment (p ≤ .032). Greater improvements (p < .001) in peak expiratory flow with BUD/FM versus BUD were seen at first measurement and maintained during 12 weeks (morning: 25.34 vs. 7.53 L/minute, respectively; evening: 21.61 vs. 7.67 L/minute, respectively); greater improvements in daily asthma symptom score and rescue medication use were also observed (p ≤ .039). Both treatments were well tolerated, with similar safety profiles. CONCLUSIONS: In this population of black asthma patients, BUD/FM pMDI resulted in greater improvements in pulmonary function and asthma control versus BUD DPI, with similar safety profiles.

Effect of budesonide/formoterol pMDI on COPD exacerbations: a double-blind, randomized study.

BACKGROUND: Treatment with an inhaled corticosteroid (ICS) and long-acting bronchodilator is recommended for severe/very severe chronic obstructive pulmonary disease (COPD) patients with repeated exacerbations. This randomized, double-blind, double-dummy, parallel-group, 12-month multicenter study evaluated the effect of budesonide/formoterol pressurized metered-dose inhaler (pMDI) on COPD exacerbations. METHODS: Following a 2-week run-in during which COPD patients aged ≥40 years with an exacerbation history discontinued medications except ICSs, 1219 patients were randomized 1:1:1 to twice-daily budesonide/formoterol pMDI 320/9 µg, budesonide/formoterol pMDI 160/9 µg, or formoterol dry powder inhaler 9 µg. An exacerbation was defined as COPD worsening requiring oral corticosteroids and/or hospitalization. A post hoc analysis, with antibiotic treatment added to the exacerbation definition, was also performed. RESULTS: Budesonide/formoterol 320/9 and 160/9 reduced exacerbation rates (number per patient-treatment year) by 34.6% and 25.9%, respectively, versus formoterol (p ≤ 0.002). Budesonide/formoterol 320/9 prolonged time to first exacerbation versus formoterol, corresponding to a 21.2% reduction in hazard ratio (0.788 [95% CI: 0.639, 0.972]; p = 0.026). Exacerbation rates (number per patient-treatment year) including antibiotic treatment (post hoc analysis) were reduced by 25.9% and 18.7% with budesonide/formoterol 320/9 and 160/9, respectively, versus formoterol (p ≤ 0.023). Both budesonide/formoterol doses were well tolerated with safety profiles similar to formoterol. Pneumonia adverse events occurred in 6.4%, 4.7%, and 2.7% of patients in the budesonide/formoterol 320/9, 160/9, and formoterol groups. CONCLUSIONS: Over 12 months, both budesonide/formoterol doses reduced the exacerbation rate (defined with or without antibiotic treatment) versus formoterol. Budesonide/formoterol pMDI is an appropriate treatment for reducing exacerbations in COPD patients with a history of exacerbations. (NCT00419744).

Efficacy of budesonide/formoterol pressurized metered-dose inhaler versus budesonide pressurized metered-dose inhaler alone in Hispanic adults and adolescents with asthma: a randomized, controlled trial.

BACKGROUND: Few clinical trials in asthma have focused on Hispanic populations. OBJECTIVE: To compare the efficacy and safety of budesonide/formoterol (BUD/FM) with BUD in an ethnically diverse group of Hispanic participants with asthma previously treated with inhaled corticosteroids (ICS). METHODS: This 12-week, randomized, double-blind, active-controlled study (NCT00419757) was designed to enroll Hispanic participants (self-reported) (≥12 years of age) with moderate to severe asthma requiring medium- to high-dose ICS. After a 2-week run-in period (low-dose BUD pressurized metered-dose inhaler [pMDI] 80 µg × 2 inhalations [160 µg] twice daily), participants with a symptom score greater than 0 (scale: 0-3) on 3 or more of 7 run-in days and forced expiratory volume in 1 second (FEV(1)) 45%-85% predicted were randomized to BUD/FM pMDI 160/4.5 µg × 2 inhalations (320/9 µg) twice daily or BUD pMDI 160 µg × 2 inhalations (320 µg) twice daily. RESULTS: Randomized participants (n = 127 BUD/FM; n = 123 BUD) were predominately Mexican (51%) or Puerto Rican (21%). During low-dose ICS run-in, the mean symptom score was 1.0; however, mean predose FEV(1) improved (2.10-2.21 L). During randomized treatment, small, but not statistically significant, improvements favored BUD/FM vs BUD (am peak expiratory flow [PEF; primary efficacy variable] 25.4 vs 19.9 L/min; pm PEF 20.6 vs 15.8 L/min; predose FEV(1) 0.16 vs 0.11 L; rescue medication use -0.7 vs -0.6 inhalations/d). Most adverse events were mild or moderate in intensity. CONCLUSIONS: Improvement in clinically relevant control end points occurred in both BUD/FM and BUD groups; both treatments were well tolerated in this Hispanic asthma population but were not significantly differentiated.

The functionality of a budesonide/formoterol pressurized metered-dose inhaler with an integrated actuation counter.

Integration of an actuation counter into pressurized metered-dose inhalers (pMDIs) can allow patients to accurately determine the remaining number of medication doses. This study was designed to assess the functionality of budesonide/formoterol (Symbicort; AstraZeneca, Dunkerque, France) pMDI with an integrated actuation counter in a clinical setting. Children aged > or =6 years, adolescents, and adults with inhaled corticosteroid-dependent asthma participated in this 6-week, randomized, open-label, multicenter study (SD-039-0743; D5896C00743). Patients were treated with budesonide/formoterol pMDI with no actuation counter (80/4.5 micrograms x 2 inhalations [160/9 micrograms] twice daily) during a 7- to 10-day run-in period. Qualifying patients were then randomized into one of three groups treated with budesonide/formoterol pMDI with actuation counter (80/4.5 micrograms x 2 inhalations [160/9 micrograms] twice daily): group 1, 96 actuations (24 days); group 2, 120 actuations (30 days); or group 3, 128 actuations (32 days). Actuation count was assessed using position of the counter arrow, patient/caregiver reports (daily log and actuation counter final reading), and device (canister plus actuation counter assembly) weight change. Patients/caregivers rated ease of device use. There was good agreement across treatment groups (n = 254) between patient/caregiver-reported actuation counts and counts determined by the angular position of the arrow. Analysis of device weight change versus other estimates of actuation counts in groups 1 and 2 indicated that the device did not undercount the number of actuations sprayed. Most patients (93%) indicated the device was "extremely easy" or "very easy" to use. Clinical functionality and reliability of the budesonide/formoterol pMDI device with an actuation counter were established.

Can patients with asthma feel inhaler therapy working right away? Two clinical trials testing the effect of timing of assessment on patient perception.

BACKGROUND: Feeling a maintenance therapy work right away may provide positive reinforcement and may offer one way to improve adherence in patients with asthma. Precise measurement is required to accurately compare the presence of this effect across clinical trial treatment groups. METHODS: Two randomized, controlled studies tested whether timing of assessment (daily vs weekly, study 1; and predose vs postdose, study 2) influenced patients' reports of whether they can feel a medication working right away (perception), and their satisfaction with this perception (satisfaction). These 2-week US-based multicenter double-blind, parallel-group studies included patients > or = 18 years of age with mild to moderate persistent asthma. In each, patients were randomized to one of two drugs with different onset profiles: budesonide/formoterol pressurized metered-dose inhaler (pMDI) 80/4.5 microg x 2 inhalations (160/9 microg) twice daily or budesonide pMDI 80 microg x 2 inhalations (160 microg) twice daily. Patients were further randomized to complete previously validated perception and satisfaction questions in a cross-over fashion, either daily and weekly (N = 123) or predose and postdose (N = 134). Patient surveys also assessed perceptions of the onset of effect of medication and their value of these perceptions. RESULTS: No significant differences were observed in patients' reports of perception, either daily versus weekly or predose versus postdose. A statistically significant difference in satisfaction was found in study 1 only, favoring weekly recall (p < 0.05), with sensitivity analysis showing no difference by treatment group (p = 0.162). Across both studies, most patients (87%) who perceived their inhaler working right away (136 of 157 patients) identified positive airway sensations. Most patients reported that feeling their medication work right away is reassuring and would help them manage their asthma. CONCLUSION: Assessment timing has no effect on patient response to the perception of feeling a medication working right away. Differences found in satisfaction levels reported with weekly versus daily recall were consistent across treatment groups, indicating that no bias was introduced in favor of either treatment group. Patients characterized the perception of feeling a maintenance therapy working right away as easier breathing and reported this perception as beneficial to patient self-care.

Asthma control in pediatric patients treated with once-daily or twice-daily nebulized budesonide inhalation suspension (Pulmicort Respules).

Composite end points may represent more meaningful assessments of asthma control compared with traditional discrete measures. The effects of budesonide inhalation suspension (BIS) on composite measures of asthma control have not been investigated. The purpose of this study was to assess changes from baseline in percentages of asthma control days (ACDs; days without asthma symptoms and rescue medication use; primary outcome), symptom-free days (SFDs), and rescue medication-free days (RFDs) with BIS treatment. We retrospectively analyzed separately data from three randomized, double-blind, placebo-controlled, 12-week studies (N = 1018) of BIS. Study I patients (4-8 years) were dependent on daily inhaled corticosteroids (ICS; n = 178). Study II patients (6 months to 8 years) were using one or more asthma medications (n = 481). Study III patients (6 months to 8 years) were using daily non-ICS asthma medication (n = 359). Patients treated with BIS showed substantial improvements from baseline in all composite variables (ACDs, 21-31% versus placebo [PBO], 10-18%; SFDs, 20-29% versus PBO, 11-18%; RFDs, 24-47% versus PBO, 12-28%). In study I, each BIS regimen statistically significantly improved all three asthma control measures versus PBO. In study II, BIS 0.5 mg twice daily (b.i.d.) improved ACDs, BIS 0.25 mg b.i.d. and 0.5 mg b.i.d. improved SFDs, and all BIS regimens improved RFDs statistically significantly. In study III, BIS 0.25 mg once daily (q.d.) improved all three measures, BIS 0.5 mg q.d. improved SFDs, and 1.0 mg q.d. improved RFDs statistically significantly. In conclusion, BIS improved composite measures of asthma control in children.

Evaluation of efficacy and safety of budesonide delivered via two dry powder inhalers.

BACKGROUND: The dry powder inhaler (DPI) device for budesonide inhalation powder 200 microg (DPI-A) was redesigned to improve dosing consistency and provide new features (budesonide inhalation powder 90 microg and 180 microg; DPI-B). OBJECTIVE: Two multicenter, parallel-group, double-blind, randomized, 12-week studies compared the efficacy and safety of budesonide delivered via each DPI versus placebo, and the systemic exposure of budesonide from each device. METHODS: Asthmatic adults with mild-to-moderate asthma (N = 621) and patients 6-17 years with mild asthma (N = 516) received budesonide DPI-B 360 microg or DPI-A 400 microg twice-daily (total daily dose 720 microg or 800 microg), budesonide DPI-B 180 microg or DPI-A 200 microg once daily (total daily dose 180 microg or 200 microg), or matching placebo. Change in forced expiratory volume in 1 second (FEV(1)) and secondary variables (asthma symptoms, beta(2)-adrenergic agonist use, peak expiratory flow [PEF], and withdrawals due to worsening asthma) versus placebo were measured. RESULTS: In both studies, FEV(1) significantly (p < 0.05) improved for all active treatments versus placebo except once-daily budesonide DPI-B 180 mug in adults. In the adult study, significantly (p < 0.05) greater improvements in all secondary variables occurred with all active treatments versus placebo. In the pediatric/adolescent study, improvements in AM/PM PEF were significantly (p or= 6 years with very mild asthma and adolescents and adults with mild-to-moderate asthma. The study is limited by the evaluation of only two doses for each product in both studies. Additionally, the studies were not designed to test equivalence or noninferiority between the active products. Pharmacokinetic characterization was limited because of the small sample sizes.

Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma.

BACKGROUND: Budesonide inhalation suspension and the leukotriene receptor antagonist montelukast have demonstrated efficacy in children with mild persistent asthma, but comparative long-term studies in young children are needed. OBJECTIVE: To compare the long-term efficacy and safety of budesonide inhalation suspension and montelukast. METHODS: After a run-in period, children 2 to 8 years old with mild asthma or recurrent wheezing were randomized to once-daily budesonide inhalation suspension 0.5 mg or once-daily oral montelukast 4 or 5 mg for 52 weeks. Subjects were stepped up to twice-daily budesonide inhalation suspension or oral corticosteroids for mild or severe asthma worsening, respectively. The primary outcome was time to first additional medication for asthma worsening at 52 weeks. Secondary variables included times to the first additional asthma medication measured at 12 and 26 weeks; times to the first asthma exacerbation (mild and severe) measured at 12, 26, and 52 weeks; exacerbation rates (mild and severe) over a period of 52 weeks; diary variables (eg, peak expiratory flow [PEF]); patient-reported outcomes; and Global Physician and Caregiver Assessments. RESULTS: No significant between-group differences were observed for time to first additional asthma medication at 52 weeks; however, time to first additional asthma medication was longer (unadjusted P = .050) at 12 weeks and exacerbation rates were lower over a period of 52 weeks (unadjusted P = .034) for budesonide versus montelukast. Time to first severe exacerbation (requiring oral corticosteroids) was similar in both groups, but the percentage of subjects requiring oral corticosteroids over a period of 52 weeks was lower with budesonide (25.5% vs 32.0%). Peak flow and Caregiver and Physician Global Assessments favored budesonide. CONCLUSION: Both treatments provided acceptable asthma control; however, overall measures favored budesonide inhalation suspension over montelukast. CLINICAL IMPLICATIONS: These findings are consistent with studies in older children demonstrating better outcomes with inhaled corticosteroids versus montelukast.

Basal and cosyntropin-stimulated plasma cortisol concentrations, as measured by high-performance liquid chromatography, in children aged 5 months to younger than 6 years.

CONTEXT: Topical corticosteroids are the recommended first-line treatment for all severities of persistent asthma and moderate to severe allergic rhinitis. Potential adrenal suppression resulting from corticosteroid administration necessitates monitoring of children participating in clinical studies. Measurement of pretreatment cortisol concentrations is necessary to assess effects on adrenal function. OBJECTIVE: Plasma cortisol concentrations are assay dependent; normal reference range values must be obtained for each assay. Our objective is to provide these values for children as determined by HPLC. DESIGN AND PATIENTS: Two multicenter, randomized, double-blind, placebo-controlled studies evaluating basal and cosyntropin-stimulated morning plasma cortisol concentrations for patients aged 5 to younger than 12 months with asthma and patients aged 2 to younger than 6 yr with allergic rhinitis using HPLC were conducted. MAIN OUTCOME MEASURES: Main planned outcomes of these studies are reported elsewhere. This manuscript reports plasma cortisol concentration reference range values. RESULTS: In general, mean basal plasma cortisol concentrations (n = 177) (mean +/- sd, nmol/liter) were similar among the 5 to younger than 9 months, 9 to younger than 12 months, 2 to younger than 3 yr, 3 to younger than 4 yr, 4 to younger than 5 yr, and 5 to younger than 6 yr age groups (218 +/- 149, 281 +/- 144, 257 +/- 105, 231 +/- 83, 298 +/- 118, and 237 +/- 65, respectively) and increased to comparable levels 60 min after cosyntropin stimulation (n = 178; 622 +/- 176, 638 +/- 176, 697 +/- 99, 655 +/- 103, 662 +/- 113, and 610 +/- 68, respectively). However, patients younger than 12 months had wider ranges of basal and stimulated values. CONCLUSIONS: Basal and cosyntropin-stimulated morning plasma cortisol concentrations of children aged 5 to younger than 12 months and 2 to younger than 6 yr were consistently measurable, with the large majority similar among the age groups examined, and comparable with those reported elsewhere for adults.

Growth velocity in children with perennial allergic rhinitis treated with budesonide aqueous nasal spray.

BACKGROUND: Recent guidelines recommend intranasal corticosteroids as first-line treatment for managing persistent symptoms of moderate to severe allergic rhinitis (AR). However, in children, long-term continual treatment with corticosteroids has raised concerns about potential growth suppression. OBJECTIVE: To evaluate the effects of the recommended once-daily dose of budesonide aqueous nasal spray on growth velocity, as measured with stadiometry, in children with perennial AR. METHODS: In this double-blind, placebo-controlled, multicenter study, 229 prepubertal children (mean age, 5.9 years; age range, 4-8 years) with perennial AR were randomized (2:1) to receive budesonide aqueous nasal spray, 64 microg (32 microg per nostril) once daily, or placebo for 1 year. The change from baseline in growth velocity, height after treatment, and the percentage of patients whose percentile for height decreased from baseline to the end of treatment were evaluated. RESULTS: Growth velocity was not significantly different between the 2 groups. The least-squares mean +/- SE growth velocity during treatment was 5.91 +/- 0.11 cm per year for children receiving budesonide and 6.19 +/- 0.16 cm per year for those receiving placebo. The mean difference in growth velocity between the 2 groups was 0.27 +/- 0.18 cm per year (95% confidence interval, -0.07 to 0.62 cm per year). After treatment, the mean +/- SD height was 128.8 +/- 8.7 cm for children receiving budesonide and 128.2 +/- 8.8 for those receiving placebo. The percentage of children whose percentile for height decreased during treatment was not significantly different between the 2 groups (budesonide, 59%, placebo, 54%; P = .64). The incidence and types of adverse events and the mean 24-hour urinary cortisol-creatinine ratio were similar for the 2 groups. CONCLUSIONS: Treatment with budesonide aqueous nasal spray, 64 microg once daily, for 1 year did not suppress growth velocity compared with placebo and was well tolerated in prepubertal children with perennial AR.