Abstract
BACKGROUND: Binge-eating disorder) BED) is the most common eating disorder in the United-States. Daily, orally administered topiramate has shown BED treatment efficacy, with two major limitations: frequent and severe side effects and slow time-to-effect. SipNose is a novel non-invasive intranasal direct nose-to-brain drug delivery platform that delivers drugs to the central nervous system consistently and rapidly. Herein, we study a SipNose-topiramate combination product, as an acute "as needed" (PRN) solution for BED management. METHODS: First, SipNose-topiramate's pharmacokinetics (PK) and safety was evaluated. The second part aimed to demonstrate its PRN-treatment feasibility in terms of usability and potential efficacy in reducing the number of binge-eating events. Twelve BED patients were studied over three time periods; 2-weeks of baseline monitoring [BL], 8-weeks of treatment [TX], and 2-weeks of follow up [FU]. RESULTS: The PK profile showed peak plasma levels at 90 min post-administration, a t(1/2) > 24 h and consistent topiramate delivery with no adverse events. In the second part, 251 treatments were self-administered by the patient participants. There was a significant reduction from baseline to treatment periods in mean weekly binge-eating events and binge-eating event days per week. This was maintained during the follow up period. Efficacy was corroborated by improved patient illness severity scales. There were no adverse events associated with any administered treatments. Patients were exposed to less drug when compared with accepted oral dosing. CONCLUSIONS: This study introduces a SipNose-topiramate drug-device combination as a potentially safe, effective, and controlled method for BED management. Its findings introduce a potential approach to BED management both as an intranasal and as a PRN therapy for reducing binge-eating events, with a large-scale reduction in patient drug exposure and side effects and with improved patient quality of life. Further studies are needed with larger patient populations to establish SipNose-topiramate as a mainstream treatment for BED. TRIAL REGISTRATION: Registration number and date of registration of the clinical studies reported in this article are as follows: 0157-18-HMO, August 15th 2018 and 6814-20-SMC, December 2nd 2020.