Person:

Hudson, James

Abstract Background: A 12-month, open-label extension study assessed the long-term safety and tolerability of lisdexamfetamine dimesylate (LDX) in adults with binge eating disorder (BED). Methods: Adults (aged 18–55 y) with BED who completed 1 of 3 antecedent studies were enrolled in a 52-week, open-label extension study (dose optimization, 4 weeks [initial titration dose, 30-mg LDX; target doses, 50- or 70-mg LDX]; dose maintenance, 48 weeks). Safety evaluations included the occurrence of treatment-emergent adverse events (TEAEs), vital sign and weight assessments, and Columbia-Suicide Severity Rating Scale responses. Results: Of the 604 enrolled participants, 599 (521 women and 78 men) comprised the safety analysis set, and 369 completed the study. Mean (SD) LDX exposure was 284.3 (118.84) days; cumulative LDX exposure duration was 12 months or longer in 344 participants (57.4%). A total of 506 participants (84.5%) reported TEAEs (TEAEs leading to treatment discontinuation, 54 [9.0%]; severe TEAEs, 42 [7.0%]; serious TEAEs, 17 [2.8%]). Treatment-emergent adverse events reported in greater than or equal to 10% of participants were dry mouth (27.2%), headache (13.2%), insomnia (12.4%), and upper respiratory tract infection (11.4%). Mean (SD) changes from antecedent study baseline in systolic and diastolic blood pressure, pulse, and weight at week 52/early termination (n = 597) were 2.19 (11.043) and 1.77 (7.848) mm Hg, 6.58 (10.572) beats per minute, and −7.04 (7.534) kg, respectively. On the Columbia-Suicide Severity Rating Scale, there were 2 positive responses for any active suicidal ideations; there were no positive responses for suicidal behavior or completed suicides. Conclusions: In this 12-month, open-label, extension study, the long-term safety and tolerability of LDX in adults with BED were generally consistent with its established profile for attention-deficit/hyperactivity disorder.

Abstract Objective: This study examined the time course of efficacy‐related endpoints for lisdexamfetamine dimesylate (LDX) versus placebo in adults with protocol‐defined moderate to severe binge‐eating disorder (BED). Methods: In two 12‐week, double‐blind, placebo‐controlled studies, adults meeting DSM‐IV‐TR BED criteria were randomized 1:1 to receive placebo or dose‐optimized LDX (50 or 70 mg). Analyses across visits used mixed‐effects models for repeated measures (binge eating days/week, binge eating episodes/week, Yale‐Brown Obsessive Compulsive Scale modified for Binge Eating [Y‐BOCS‐BE] scores, percentage body weight change) and chi‐square tests (Clinical Global Impressions—Improvement [CGI‐I; from the perspective of BED symptoms] scale dichotomized as improved or not improved). These analyses were not part of the prespecified testing strategy, so reported p values are nominal (unadjusted and descriptive only). Results: Least squares mean treatment differences for change from baseline in both studies favored LDX over placebo (all nominal p values < .001) starting at Week 1 for binge eating days/week, binge‐eating episodes/week, and percentage weight change and at the first posttreatment assessment (Week 4) for Y‐BOCS‐BE total and domain scores. On the CGI‐I, more participants on LDX than placebo were categorized as improved starting at Week 1 in both studies (both nominal p values < .001). Across these efficacy‐related endpoints, the superiority of LDX over placebo was maintained at each posttreatment assessment in both studies (all nominal p values < .001). Discussion In adults with BED, LDX treatment appeared to be associated with improvement on efficacy measures as early as 1 week, which was maintained throughout the 12‐week studies.

The efficacy and safety of lisdexamfetamine dimesylate (LDX) vs placebo in binge eating disorder (BED) was evaluated in two multicenter, double-blind, placebo-controlled trials. Adults (study 1, n=383; study 2, n=390) meeting DSM-IV-TR BED criteria were randomized (1:1) to placebo or LDX (50 or 70 mg/day) dose titration; optimized doses were maintained to the end of double-blind treatment (week 12/early termination). Change from baseline in binge eating days/week at weeks 11−12 (primary efficacy endpoint) was assessed with mixed-effects models for repeated measures. Secondary endpoints related to binge eating and medical parameters, safety, and treatment compliance were also assessed. Least squares mean (95% CI) treatment differences for change from baseline binge eating days/week at weeks 11–12 significantly favored LDX (study 1: –1.35 [–1.70, –1.01] study 2: –1.66 [–2.04, –1.28] both P<0.001). In both studies, treatment-emergent adverse events (TEAEs) reported by ⩾10% of LDX participants were dry mouth, insomnia, and headache. Serious TEAEs occurred in two (1.1%) placebo participants in each study and in three (1.6%) and one (0.6%) LDX participants in study 1 and study 2, respectively. Across studies, mean increases from baseline at week 12/early termination with LDX for pulse and systolic and diastolic blood pressure ranged from 4.41–6.31 b.p.m. and 0.2–1.45 and 1.06–1.83 mm Hg, respectively. LDX (50 and 70 mg/day) was superior to placebo in decreasing binge eating days/week from baseline and improving binge eating–related key secondary endpoints. Safety results appear consistent with the known safety profile of LDX.