Research Project
8211426
DESCRIPTION (provided by applicant): There is a significant unmet medical need to provide additional pharmacologic treatments for treatment and prevention of opioid overdose. This Fast Track STTR project proposes to apply drug delivery technologies to develop a novel use for a nasally delivered pharmaceutical - naloxone (NLX) hydrochloride - for the emergency treatment of opioid overdose by emergency medical services. Emergency medical service personnel would prefer a non-injection based antidote to avoid accidental needle-sticks in the revival of opioid overdose victims. This approach would markedly reduce the risks of contracting hepatitis or HIV by first responders. It might also reduce time to first treatment by obviating the need to establish an injection site and preparation of the injectable device or intravenous access. The specific objective is to create a nasal spray that offers a novel therapeutic option for a rapid-acting, interventional medication intended to acutely reverse the effects of prescription (e.g Oxycontin(R)) and illicit opioids (e.g heroin). The hypothesis of this project is that nasally delivered NLX will have biopharmaceutics comparable to NLX subcutaneous (SC) and intramuscular (IM) injection, without the use of a needle. The project hypothesis will be tested by the following Specific Aims: 1. Develop prototype formulations of NLX meeting standards for potency &stability 2. Manufacture the preferred formula and complete product stability testing 3. Manufacture animal and human clinical testing batches of NLX nasal spray 4. Assess upper and lower airway toxicity in vivo to beagle pups 5. Conduct a bioavailability study comparing the nasal spray system to SC and IM injection in healthy human volunteers For Phase 1 (aim 1), formulation chemistry (see Section 5 Aim 1) will be applied to design chemically stable, microbiologically safe nasal delivery formulae for delivery by a unit-dose nasal spray device. For Phase 2 (aim 2), the pilot formula will be manufactured into the sprayer and have formal stability testing completed. For aim 3 the naloxone nasal spray product will be manufactured for animal and human testing. The formula will be administered in vivo to beagle pups, in order to test upper and lower airway toxicity (aim 4). For Phase 2 (aim 5), an IND will be filed with FDA and nasally delivered NLX biopharmaceutics will be attained by manufacture of a NLX nasal spray batch of the selected prototype formula and conducting a pilot bioavailability study in healthy human volunteers. Milestones for this project include the development of stable formulae, selection of a final formula and stability testing of the manufactured product, production of the NLX nasal spray for preclinical and human studies, no, or reversible irritation in beagle pups, and attainment of rapid absorption and bioavailability in human comparable to SC and IM injection. PUBLIC HEALTH RELEVANCE: There is a significant unmet medical need to provide additional pharmacologic treatments for treatment and prevention of opioid (morphine like medications) overdose. The specific objective is to create a nasal spray that offers a novel therapeutic option for a rapid-acting, interventional medication intended to acutely reverse the effects of prescription (e.g Oxycontin(R)) and illicit opioids (e.g heroin).
