title: Safety of formoterol after cumulative dosing via Easyhaler and Aerolizer.
abstract: This randomised, double-blind, double-dummy, cumulative dose, multicentre crossover study aimed to demonstrate non-inferiority in safety of formoterol delivered via Easyhaler versus Aerolizer. The secondary objective was to compare the efficacy of the devices. Thirty-three adult asthmatic subjects entered the study and 32 completed it. The study comprised screening and two study days, with each subject inhaling 96 microg (12, 12, 24 and 48 microg) cumulative dose of formoterol via the study inhalers. Serum potassium (S-K+), vital signs and spirometry were performed at baseline, 1h after each dose and additionally 4h after the last dose. The primary safety variable was S-K+. Secondary safety variables were heart rate, corrected QT interval, blood pressure, serum glucose and adverse events. Spirometry was assessed to evaluate efficacy. The results showed non-inferiority in safety of formoterol inhaled via Easyhaler compared to Aerolizer. The adjusted treatment difference in the S-K+ values after 96 microg cumulative dose of formoterol was 0.14 mmol/L being clearly above the pre-determined lower limit of the non-inferiority criterion of -0.2 mmol/L. There were dose-related changes in secondary efficacy variables after both treatments. The changes were comparable in most of the parameters but heart rate was statistically significantly higher and decrease in diastolic blood pressure greater after formoterol via Aerolizer than that via Easyhaler. The occurrence of adverse events was dose-related, the most common events being tremor, hypokalaemia, headache and palpitation. The spirometry results showed no statistically significant difference in efficacy between the treatments. In conclusion, formoterol delivered via Easyhaler was as safe as via Aerolizer.
authors.affiliation: Kuopio University Hospital, P.O. Box 1777, 70211 Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Randell
authors.forename: A
authors.initials: A
authors.lastname: Saarinen
authors.forename: M
authors.initials: M
authors.lastname: Walamies
authors.forename: M
authors.initials: M
authors.lastname: Vahteristo
authors.forename: M
authors.initials: M
authors.lastname: Silvasti
authors.forename: S
authors.initials: S
authors.lastname: Lähelmä
mesh_terms: D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000336:Aerosols; D000368:Aged; D000403:Airway Resistance / Q000187:drug effects; D000704:Analysis of Variance; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D015999:Multivariate Analysis; D016896:Treatment Outcome
chemical_list: D000318:Adrenergic beta-Agonists; D000336:Aerosols; D004983:Ethanolamines; D000068759:Formoterol Fumarate