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).
Thesaurus Terms: "aids Virus; Absorption; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Acute; Address; Animals; Antidotes; Bioavailability; Biologic Availability; Biological Availability; Biopharmaceutics; Blood; Boots Brand Of Naloxone Hydrochloride; Bristol-Myers Squibb Brand Of Naloxone Hydrochloride; Chemistry; Clinical Evaluation; Clinical Research; Clinical Study; Clinical Testing; Contin, Ms; Contracting Opportunities; Contracts; Data; Development; Devices; Diacetylmorphine; Diamorphine; Dihydrohydroxycodeinone; Dose; Drug Delivery; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Drug Targeting; Drug Targetings; Drugs; Drugs, Investigational; Emergencies; Emergency Situation; Emergency Medical Service; Emergency Treatment; Endo Brand Of Naloxone Hydrochloride; Fda; Food And Drug Administration; Food And Drug Administration (U.S.); Formulation; Formulations, Drug; Hiv; Htlv-Iii; Health Care Providers; Health Personnel; Healthcare Providers; Healthcare Worker; Hepatitis; Heroin; Human; Human Immunodeficiency Viruses; Human Resources; Human T-Cell Leukemia Virus Type Iii; Human T-Cell Lymphotropic Virus Type Iii; Human T-Lymphotropic Virus Type Iii; Human Volunteers; Human, General; Infumorph; Injectable; Injection Of Therapeutic Agent; Injections; Intramuscular; Intramuscular Injections; Intravenous; Investigation; Investigational Drugs; Investigational New Drug Application; Investigational New Drugs; Kadian; Lav-Htlv-Iii; Lamepro Brand Of Naloxone Hydrochloride; Life; Lymphadenopathy-Associated Virus; Msir; Mammals, Rabbits; Man (Taxonomy); Man, Modern; Manpower; Medical; Medication; Morphia; Morphinan-3,6-Diol, 7,8-Didehydro-4,5-Epoxy-17-Methyl- (5alpha,6alpha)-; Morphinan-3,6-Diol, 7,8-Didehydro-4,5-Epoxy-17-Methyl- (5alpha,6alpha)-, Diacetate (Ester); Morphinan-6-One, 4,5-Epoxy-14-Hydroxy-3-Methoxy-17-Methyl-, (5alpha)-; Morphinan-6-One, 4,5-Epoxy-3,14-Dihydroxy-17-(2-Propenyl)-, (5alpha)-; Morphine; Naloxone; Naloxone Hydrochloride; Narcan; Narcanti; Nasal; Needle-Stick Injuries; Needle-Sticks; Needles; Needlestick Injuries; Needlesticks; Nose; Nose, Nasal Passages; Opioid; Oramorph; Oramorph Sr; Oryctolagus Cuniculus; Outcome; Overdose; Oxycodeinon; Oxycodone; Oxycodone Sr; Oxycontin; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Preparations; Pharmaceuticals; Pharmacokinetics; Pharmacologic Substance; Pharmacological Substance; Phase; Physiologic Availability; Preparation; Prevention; Process Of Absorption; Production; Property; Property, Loinc Axis 2; Rabbit, Domestic; Rabbits; Respiratory System, Nose, Nasal Passages; Reticuloendothelial System, Blood; Risk; Route; Roxanol; Roxicodone; Sttr; Safety; Science Of Chemistry; Site; Small Business Technology Transfer Research; Solutions; Statex Sr; System; System, Loinc Axis 4; Technology; Testing; Therapeutic Intervention; Therapy, Emergency; Theriacs; Time; Toxic Effect; Toxicities; Usfda; United Drug Brand Of Naloxone Hydrochloride; United States Food And Drug Administration; Virus-Hiv; Absorption; Base; Bioavailability Of Drug; Clinical Test; Design; Designing; Drug/Agent; Emergency Service; Emergency Service Personnel; Emergency Service Responder; Emergency Service/First Responder; First Responder; Health Care Personnel; Health Care Worker; Health Provider; Healthcare Personnel; In Vivo; Intervention Therapy; Intramuscular Administration Of Drug; Irritation; Medical Personnel; Meetings; New Therapeutics; Next Generation Therapeutics; Novel; Novel Therapeutics; Opiate Abuse; Opioid Abuse; Patient Population; Personnel; Phase 3 Study; Pre-Clinical; Preclinical; Preclinical Study; Prototype; Public Health Relevance; Pup; Research Clinical Testing; Stability Testing; Subcutaneous; Treatment Provider; Volunteer"
