title: A Comparison of Short-Term Growth During Treatment with Two Dry Powder Combinations of Inhaled Corticosteroids and Long-Acting β₂-Agonists.
abstract: BACKGROUND
  A combination of the inhaled corticosteroid budesonide and the long-acting β2-agonist formoterol has been formulated in a novel dry powder inhaler, Spiromax(®). The objective was to compare lower leg growth in children with asthma treated with inhaled budesonide+formoterol (BF) delivered from the Spiromax inhaler with BF from the Symbicort Turbohaler(®).
  
  
  METHODS
  Prepubescent children with persistent asthma (n=75, aged 6-11 years) were included in a randomized, double-blind, double-dummy, placebo-controlled, three-way crossover study with active treatment and placebo periods of 2 weeks duration. Lower leg length was measured every second week. As a secondary outcome parameter, 24-hr urine was collected for assessment of free cortisol. Interventions were dry powder BF 160+9 μg twice daily (b.i.d.; delivered dose) from the Spiromax inhaler and dry powder BF 200+12 μg b.i.d. (metered dose) from the Symbicort Turbohaler.
  
  
  RESULTS
  The least squares mean difference in lower leg growth rates (LLGR) between BF Spiromax and Symbicort Turbohaler was -0.086 mm/week [95% confidence interval (CI) -0.203, 0.032]. The pre-specified non-inferiority margin was -0.200 mm/week, so the lower limit of the 95% CI was just outside this margin. The difference between BF Spiromax and placebo was -0.20 mm/week (95% CI: -0.322, 0.086); p<0.001), between Symbicort Turbohaler and placebo -0.118 mm/week (95% CI: -0.236, -0.001; p=0.048). No statistically significant differences were seen in urine free cortisol assessments.
  
  
  CONCLUSIONS
  As the lower limit of the CI of LLGR was marginally outside of the pre-specified non-inferiority margin between BF Spiromax 160+9 μg b.i.d. and Symbicort Turbohaler 200+12 μg b.i.d., non-inferiority could not be demonstrated. Further studies may be needed for comparison of systemic activity of BF Spiromax and Symbicort Turbohaler in children before firm conclusions about their comparability may be drawn.
authors.affiliation: 1Asthma and Allergy Clinic, Children's Clinic Randers, Randers, Denmark.
authors.forename: Ole D
authors.initials: OD
authors.lastname: Wolthers
authors.affiliation: 2TEVA, Global Respiratory Research and Development, Horsham, Pennsylvania.
authors.forename: Tushar
authors.initials: T
authors.lastname: Shah
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000367:Age Factors; D000886:Anthropometry; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000652:urine; D000069502:Budesonide, Formoterol Fumarate Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D018592:Cross-Over Studies; D003718:Denmark; D004311:Double-Blind Method; D058995:Dry Powder Inhalers; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D016018:Least-Squares Analysis; D007866:Leg / Q000254:growth & development*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D012307:Risk Factors; D046468:Sexual Development; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D015415:Biomarkers; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D006854:Hydrocortisone
keywords: adrenal function; asthma; inhaled therapy; knemometry; systemic activity