Title : The critical role of lung safety in regulatory approval of systemic inhalation delivery products
Abstract:
In systemic inhalation delivery, the respiratory tract is used as a route of administration, allowing the active ingredient to enter the blood circulation directly through the alveoli. It is not for lung diseases, but for the treatment of other diseases of the body. As a potential alternative roue to intravenous administration, systemic inhalation delivery offers obvious clinical benefits. Compared with oral administration, it delivers the API into blood rapidly and avoids the first-pass effect. Compared with injection, it is non-invasive, painless, and can be self-administered. However, only four systemic inhalation delivery products have been approved so far (one withdrawn), mainly because of FDA's concerns on safety of the lungs. It is very reluctant to see patients suffer unnecessary impairment to their otherwise healthy lungs while treating other diseases. LPI-1503, Ondansetron Inhalation Powder, is developed by LUXENA Pharmaceuticals for acute treatment of nausea/vomiting. A phase I clinical trial to study pharmacokinetics and safety of LPI-1503 is recently finished. In this presentation, the presenter will discuss the critical role of lung safety in LUXENA’s communication with FDA, review the bioavailability and lung safety data of the four approved products, and present the animal toxicology (including respiratory toxicology) and clinical pharmacokinetic and safety data (including clinical safety endpoints of pulmonary functions) of LPI-1503. It is found that, by inhalation administration of LPI-1503, ondansetron can enter into blood rapidly, efficiently and safely. In 5 minutes, the blood concentration of ondansetron reached to plateau level that comparable to Cmax of orally administrated ondansetron, while latter took more than 1 hour, The bioavailability of inhaled ondansetron is calculated to be 85.7% ± 5.9%, which is much higher than orally administrated ondansetron (~50%), and other systemic inhalation delivery products (<=33%). There were no changes in lung function endpoints (FEV1 and SpO2), and no IP-related adverse events.
