(100) Results From a Pilot Study Evaluating a Novel Naloxone Nasal Swab

Introduction:

Fueled in part by the current COVID-19 pandemic and the prevalence of synthetic opioids, drug overdose deaths continue to increase with opioid overdoses accounting for over 70% of deaths1. First approved by the FDA in 1971, naloxone is indicated for the emergency treatment of opioid overdose. Current naloxone products are only available by prescription and experience barriers around accessibility and affordability2. In an effort to democratize naloxone availability, the U.S. FDA has called for an over-the-counter (OTC) naloxone3. The intranasal route is a clinically effective method for naloxone delivery, providing rapid absorption and onset of action4. This study seeks to evaluate the potential of a novel nasal swab to deliver naloxone with absorption and, onset of action at least equal to that of currently available IM and nasal spray products while addressing issues of accessibility and affordability by seeking OTC approval.

Method
A multi-phase, inpatient crossover study to compare the bioavailability and plasma concentration levels of an intranasal naloxone swab at early time points post-delivery (within the first 15 minutes) with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg) in healthy subjects and to determine the safety and tolerability of intranasal naloxone swab doses (4, 8, and 12mg), particularly with respect to nasal irritation (erythema, edema, and erosion) and olfactory nerve abnormalities in 10 healthy subjects. Qualified subjects received three separate treatments of a single 12 mg dose, two 12 mg doses, or two 8 mg doses where a naloxone nasal swab is administered into one nostril of the nasal cavity then using finger and thumb to squeeze outside of both nostrils, following a 10 hour overnight fast. These results were compared to an earlier phase where subjects received a single 0.4 mg IM naloxone injection (1 mL of 0.4 mg/mL injection, administered into the gluteus maximus muscle using a 23-gauge needle) and a single 4 mg intranasal naloxone spray, administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use).

Results
Ten healthy volunteers were enrolled for this phase with the single dose 12mg nasal swab demonstrating higher early plasma concentrations compared to intranasal spray (over 250% higher partial AUC at 2.5 min). The Tmax was comparable (Tmax 0.26 hr) to a single 0.4mg/mL IM injection (Tmax 0.25) and faster onset than a single 4mg intranasal spray (Tmax 0.45 hr) as well as superior absorption to both IM injection and intranasal spray as demonstrated by pAUC at 2.5 min (31.18 pg*hr/mL versus 4.19 pg*hr/mL and 11.81 pg*hr/mL). Adverse events were mild for all treatments and no SAEs were observed during this phase of the study.

Conclusions
A novel nasal swab applicator is an effective and well tolerated means of delivering naloxone that is comparable to or exceeds key PK measures of existing approved products. Providing safe and effective medication delivery in an over-the-counter nasal swab, offers the potential to address barriers of accessibility and affordability currently associated with prescription naloxone products.

References: 1. Stephenson, Joan. Drug overdose deaths head towards record number in 2020, CDC warns. JAMA Health Forum. 2020; 1(10): e201318.

2. Evoy KE, Hill LG, Davis CS. Considering the potential benefits of over the counter naloxone. Integ Pharm Res Pract. 2021; 10:13-21.

3. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-unprecedented-new-efforts-support-development-over. Accessed online 9/17/2021

4. Sabzghabaee AM, Eizadi-Mood N, Yaraghi A, et al., Naloxone therapy in opioid overdose patients: intranasal or intravenous? A randomized clinical trial. Arch Med Sci. 2014;10(2):309-314.

Diversity, Equity, and Inclusion: The results of this study outlines the development of a novel method for administering naloxone for the treatment of opioid overdose that seeks to address the challenge of affordability, accessibility and stigma. Current prescription naloxone products are often cost prohibitive or inaccessible for socioeconomically challenged populations and traditionally underserved populations, including geographically underserved rural communities. By developing a low cost, over-the-counter naloxone product that could be obtained at gas stations or convenience stores or ordered online at a fraction of the price of current products, individuals can bypass current medical service and retail pharmacy service models, thus improving access to life saving rescue medication in all communities.