A Novel Faster-Acting, Dry Powder-Based, Naloxone Intranasal Formulation for Opioid Overdose

Objective To examine the pharmacokinetics and safety of FMXIN001, a new intranasal powder-based naloxone formulation, in comparison to Narcan (R) nasal liquid spray. Methods FMXIN001, was developed by blending drug microspheres with larger lactose monohydrate particles, that serve as diluent and carrier, as well as a disaggregating agent. Scanning electron microscopy and X-ray were used to characterize the formulation and in vitro deposition was investigated using a nasal cast. We compared the pharmacokinetics and safety of FMXIN001 versus Narcan (R) in two clinical trials: a pilot study with 14 healthy adults and a pivotal trial in 42 healthy adults (NCT04713709). The studies were open-label, single-dose, randomized, two-period, two-treatment, two-sequence crossover studies to assess the pharmacokinetics and safety of FMXIN001 versus Narcan (R) nasal spray. Results FMXIN001 comprises naloxone microspheres (5-30 mu M) and lactose particles (40-240 mu M). Upon in vitro testing, naloxone deposits mainly to the middle turbinates region and the upper part of the nasal cavity of a nasal cast. In human subjects, FMXIN001 produced significantly higher exposure at the initial time points of 4, 10, and 30 min, post-administration, compared to Narcan (R). Both treatments were safe and well tolerated. FMXIN001, powder-based spray, results in similar overall exposure to Narcan (R), but with more rapid absorption in the first 30 min. Conclusions FMXIN001 is expected to have a shorter onset of action for a more effective therapeutic intervention to manage opioid overdose. Rapid administration of naloxone in cases of opioid overdose is imperative, given the alarming increase in mortality rates.

Automated summary

This study compares the pharmacokinetics and safety of a new intranasal powder-based naloxone formulation (FMXIN001) with Narcan (R) nasal liquid spray. The results show that FMXIN001 has higher exposure and is well tolerated. It is expected to have a shorter onset of action for a more effective management of opioid overdose.