DM1 is a polynucleotide repeat disorder with multisystemic and central nervous system manifestations. CNS manifestations include daytime sleepiness and fatigue. It has been proposed that the dysregulation of the GABA-A neurotransmitter system or increased prevalence of GABA-A receptor subunits could play a role in CNS sleepiness and fatigue. Flumazenil, a selective benzodiazepine binding site antagonist has been reported to be effective for the therapy of idiopathic hypersomnia (IH) (Trotti-2016). Open-label treatment of IH patients using flumazenil administered by various delivery routes showed sustained clinical benefit in 39% of IH patients.

12 participants with adult onset DM1, excessive daytime sleepiness (Epworth scale > 11 or sleep duration < 10 hr day) and if present, optimally treated mod/severe sleep apnea, were enrolled. Cohort 1 (n=7) was randomly assigned to 1 mg ERX-963 vs placebo at visit 1 and the crossover treatment at visit 2; Cohort 2 (n=5) was randomized to 2 mg ERX-963 vs placebo. Outcome measures include: pharmacokinetic sampling, Stanford Sleepiness Scale (SSS), Psychomotor Vigilance Test (PVT) and one-back working memory test performed at baseline and every 30 min over 3 hr, continuous EEG, and Patient and Clinician Global Impression of Improvement (PGI-I, CGI-I).

While ERX-963 at 1 mg and 2 mg was safe, there was no evidence of efficacy in measures of sleepiness or vigilance with this dose and administration regimen.