0578 Clinician and Patient Global Impression in a Phase 2 Study of Mazindol (NLS-1021) in Adults with Narcolepsy Type 1 and Type 2

Abstract

Abstract Introduction Mazindol is the first partial orexin 2 receptor agonist and triple monoamine reuptake inhibitor in development for the treatment of narcolepsy. Clinician and Patient Global Impression (CGI and PGI, respectively) for cataplexy and excessive daytime sleepiness were assessed as secondary endpoints in the phase 2 (POLARIS, NLS-1021) multicenter study of mazindol ER in adult participants with narcolepsy type 1 (NT1) or type 2 (NT2) (ClinicalTrials.gov Identifier: NCT04923594). Methods Adults diagnosed with NT1 or NT2 who were washed out of narcolepsy medications at baseline were included into the study. Patients were treated with mazindol ER (NLS-2) at once-daily 2 mg for one week and once-daily 3 mg thereafter or matching placebo (PBO) on a 1:1 ratio. Throughout the study, CGI Severity (CGI-S) and PGI Severity (PGI-S) for cataplexy severity and excessive daytime sleepiness, respectively, were assessed and compared with scores at baseline. Both scales have five levels of severity: “None”, “Mild”, “Moderate”, “Severe”, or “Very Severe.” Results Sixty-seven participants were randomized (NT1 33.3% in NLS-2 group; 35.3% in PBO). At baseline, the mean CGI-S – Cataplexy was approximately 3.7 and CGI-S – Sleepiness approximately 3.4. Despite the small sample size, at the end of the double-blind (DB) period, the NLS-2 group demonstrated clinically and statistically significant improvements vs. PBO in both CGI-S – Sleepiness (d = –0.7, p = 0.016) and CGI-S – Cataplexy (d = –0.8, p = 0.020). At baseline, the mean PGI-S – Cataplexy was approximately 3.2 and PGI-S – Sleepiness approximately 3.7. At the end of the DB period, the NLS-2 group demonstrated clinically and statistically significant improvements vs. PBO in both PGI-S – Sleepiness (d = –0.8, p = 0.007) and PGI-S – Cataplexy (d = –0.8, p = 0.023). Conclusion Mazindol ER resulted in significant improvements of cataplexy severity and sleepiness in both conditions as rated by both clinicians and participants. These secondary outcome results support the efficacy of mazindol ER on cataplexy attacks, in NT1 participants, and on sleepiness, in NT1 as well as in NT2 participants. Support (if any) NLS Pharmaceutics