113 Dasotraline for the Treatment of Moderate to Severe Binge Eating Disorder in Adults: Results From a Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Objectives: Binge eating disorder (BED) is themost common eating disorder in the US, with a lifetimeprevalence of 2.8%. Disturbances in reward circuitry havebeen implicated in its pathogenesis. Dasotraline is a noveland potent dopamine and norepinephrine reuptake inhibitor with slow absorption and a long half-life resulting instable plasma concentrations over 24 hours with once-dailydosing. This study evaluated the efficacy and safety offlexibly-dosed dasotraline (4, 6, and 8 mg/day) vs placeboin adults with moderate to severe BED over a 12-weekperiod (NCT02564588).METHODS: Key inclusion criteria included moderate tosevere BED based on a history of =2 binge eating days/week for =6 months prior to screening, and =3 bingeeating days for each of2 weeks prior to randomization, asdocumented in participant's binge eating diary. Patientswere randomized 1:1 to flexibly-dosed dasotraline (4, 6,8 mg/day) or placebo. Theprimary endpoint was changefrom baseline (CFB) in the number of binge eating daysper week at Week 12. Key secondary endpoints were:CFB in Clinical Global Impression-Severity (CGI-S)Scale at Week 12; CFB in Yale-Brown ObsessiveCompulsive Scale Modified for Binge Eating (YBOCSBE) at Week 12; and the percentage ofsubjects with a4-week cessation from binge eating prior to Week 12 orend of treatment (EOT). Except for 4-week cessation, theother three variables were analyzed using amixed modelfor repeated measures (MMRM).RESULTS: 317 subjects (84% female) received =1 dose ofstudy medication (mean age was 38.2 years; meannumber of binge eating days per week, 4.25; mean CGIS score, 4.5; mean BMI, 34.7). The MMRM analysis ofCFB at Week 12 in the number of binge days/weekyielded a significant mean difference of-0.99 (95% CI:-0.65 to-1.33; p < 0.001) infavour of dasotraline (-3.74in the dasotraline group vs-2.75 in the placebo group).All three key secondary endpoints were met at Week 12or EOT: 46.5% of subjects in thedasotraline groupachieved at least 4 consecutive weeks' cessation frombinge eating vs 20.6% in the placebo group (p < 0.001);CFB in CGI-S and YBOCS-BE scores were also statistically significant in favour of dasotraline (p < 0.001). Thetreatment-emergent adverse events (TEAEs) thatoccurred more frequently with dasotraline vs placebo at>2% incidence included: insomnia (44.6% vs 8.1%), drymouth (27.4% vs 5.0%), decreased appetite (19.7% vs6.9%), anxiety (17.8% vs 2.5%), nausea (12.7% vs 6.9%)and decreased body weight (12.1% vs 0%). Discontinuation due to AEs occurred in 11.5% of patients takingdasotraline vs 2.5% taking placebo.CONCLUSIONS: In adults with moderate to severe BED,there were highly significant and clinically meaningfulreductions with dasotraline vs placebo in the frequencyof binge eating, global severity of illness, and obsessivecompulsive symptoms related to binge eating. Theseresults suggest dasotraline may offer a novel, welltolerated and efficacious treatmentfor BED.