An open-label trial to investigate the dose delivery and tolerability of inhaled dry powder mannitol (IDPM) using low output and high output Orbital™ inhalers across defined flow rates in healthy volunteers

INTRODUCTION: Current dry powder inhalers (DPIs) typically deliver up to 30mg as the emitted powder mass. The Orbital™ DPI is a disposable, single-use, pre-filled product being developed to deliver 400mg of mannitol to the lung via a number of inhalations. The assessment of emitted powder mass and tolerability is the focus of this trial. METHODS: Open-label trial in healthy subjects >18 years with baseline FEV1 >70% of predicted to determine the tolerability and dose delivery of IDPM across two defined flow rates using low and high output Orbital DPIs. Subjects who completed a full inhalation at any flow rate at Visit 1 progressed to Visit 2 at which time up to a maximum dosage of 400mg of IDPM was administered by sequential inhalations. RESULTS: The single inhalation shot weights from the sequential assessments are shown in Table 1. For the Visit 2 procedure, the mean number of inhalations required to empty the DPI was 7.5 (SD 1.76; Range 5-12). The mean shot weight per inhalation was 43mgs, mean cumulative shot weight after 5 inhalations was 300mgs (SD 36). View this table: Visit 1 shot weights (mgs) CONCLUSION: Compared to convential DPIs, the Orbital DPI is capable of delivering many-fold greater masses of dry powder over repeated inhalations. Further development is warranted to investigate the upper limits of dose delivery and to examine the utility of the device with other engineered particles.