P86 In vitro and clinical characterisation of the antistatic valved holding chamber aerochamber plus® flow-vu® for administrating tiotropium respimat® in 1–5-year-old children with persistent asthmatic symptoms

Introduction Characterisation of any inhalation product requires a comprehensive assessment including in vitro , pharmacokinetic (PK), and clinical Results We assessed tiotropium Respimat ® administered with the AeroChamber Plus ® Flow-Vu ® antistatic valved holding chamber (test VHC) using in vitro , PK and clinical data in 1–5 year-olds with persistent asthmatic symptoms. Methods We evaluated tiotropium delivered into a cascade impactor under fixed paediatric flow rates with and without holding times in the test VHC. Tidal breathing simulations and an anatomically correct ADAM-III Child Model were employed to assess the tiotropium mass likely to reach the lungs of preschool children when Respimat ® was administered with the test VHC. Clinical characterisation was based on a 12 week, randomised trial of once-daily tiotropium Respimat ® or placebo as add-on to background therapy in 1–5 year-olds with persistent asthmatic symptoms (NCT01634113). PK data on systemic exposure to tiotropium Respimat ® administered with test VHC in preschool children were compared with pooled data from older patients with symptomatic persistent asthma not using VHCs (NCT01383499/NCT01122680/NCT01233284/NCT01152450/NCT01696071/NCT00772538/NCT00776984/NCT01172808/NCT01172821). Results In vitro emitted mass decreased with lower flow conditions, indicating age-dependent dose reduction. In terms of dose per kg/body weight, delivered dosing at flow rates corresponding to preschool children was comparable to that at flow rates corresponding to older children (Table). Transmission and holding properties of tiotropium Respimat ® administered by test VHC were fully sufficient for aerosol delivery of patients. Standardised tidal inhalation resulted in emitted mass from the test VHC of approximately one-third of labelled dose, independent of coordination and face mask use, indicating predictable tiotropium administration by Respimat ® when used with test VHC. ADAM-III model data correlated well with standardised tidal breathing Results in terms of total mass delivered and mass delivered to filter (available to lungs). In separate clinical trials, tiotropium exposure in 1–5 year-old patients using the test VHC, adjusted by height or body surface, was comparable with that observed in older patients not using VHCs, with no overexposure. Safety of tiotropium Respimat ® in 1–5 year-olds was comparable to placebo. Conclusion This study supports administration of tiotropium Respimat ® with the AeroChamber Plus ® Flow-Vu ® VHC in 1–5 year-old children with persistent asthmatic symptoms.