Using a combination of In-Silico Lung Deposition Modelling and Secondary Endpoint Data taken from a Phase 3 Clinical Trial in patients with Severe Asthma, to provide evidence that Lung Deposition may be Enhanced when using a Smart Nebuliser instead of a Conventional Nebuliser

Sandy Munro


Achieving good lung deposition is key to disease treatment using inhaled medicines. Different inhalation delivery systems may give differing amounts and patterns of deposition for a given dose. Functional Respiratory Imaging (FRI), which combines data from high resolution computed tomography (CT) scans with computational fluid dynamics (CFD) flow simulations, can be used to probe differences in lung deposition in-silico for different delivery devices. In this study, the AKITA® JET smart nebuliser (Vectura, Chippenham, UK) was compared against a conventional jet nebuliser using FRI and these results were, in turn, compared with various secondary endpoint outcomes from a Phase III clinical trial which was also comparing the AKITA® JET to a conventional nebuliser (CN). 

CT images of the lungs of 10 subjects primarily with severe asthma were used to create 3D computational models. The models were subjected, in-silico, to representative aerosols, inhaled via idealised realistic manoeuvres, from the two devices: AKITA® JET and the PARI LC® Sprint (Conventional Nebuliser [CN], PARI, Midlothian, VA, USA). In the lung deposition modelling experiments, the AKITA® JET achieved greater lung deposition (especially to the peripheral airways), than was achieved for the CN.  

The VR475 Phase III clinical trial outcomes (EudraCT 2015-000353-20) provide further evidence to support the in-silico results. The trial compared outcomes between subjects receiving budesonide or placebo administered using the AKITA® JET, with those for subjects receiving budesonide via CN. Although the trial did not meet its primary endpoint (clinically significant reduction in exacerbations), there was a trend towards improved forced expiratory volume in 1 second (FEV1) and forced expiratory flow at 25–75% of forced vital capacity (FEF25–75) for the AKITA® JET versus CN, with statistically significant differences at some time points.

Key Message

The in-silico lung deposition modelling experiments indicate that the AKITA® JET may be able to achieve greater and deeper lung deposition than CN for a given dose and these results were further supported by a number of the secondary endpoint measures in the VR475 Phase III study referenced above.

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