Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial

Abstract

Importance: The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important.

Objective: To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder.

Design, setting, and participants: A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions-Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase.

Interventions: Lisdexamfetamine administration.

Main outcomes and measures: The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events.

Results: Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over placebo on the log-rank test (χ21, 40.37; P < .001) for time to relapse; the hazard ratio, based on a Cox proportional hazards model for lisdexamfetamine vs placebo, was 0.09 (95% CI, 0.04-0.23). The treatment-emergent adverse events observed were generally consistent with the known profile of lisdexamfetamine.

Conclusions and relevance: Risk of binge-eating relapse over 6 months was lower in participants continuing lisdexamfetamine than in those randomized to placebo. The hazard for relapse was lower with lisdexamfetamine than placebo.

Trial registration: clinicaltrials.gov Identifier: NCT02009163.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Hudson has received consulting fees and grant support from Shire Development LLC. In addition, he has received consulting fees from diaMentis, Genentech, Pronutria Biosciences, F. Hoffmann-LaRoche Ltd, and Sunovion Pharmaceuticals, as well as grant support from Genentech and Sunovion Pharmaceuticals. Dr McElroy is a paid consultant for and has received grant support from Shire Development LLC; a consultant for or member of the scientific advisory boards of Alkermes, Bracket, Corcept, F Hoffmann-LaRoche Ltd, Ironshore, MedAvante, Mitsubishi Tanabe America, Myriad, Naurex, Novo Nordisk, Sunovion Pharmaceuticals, and Teva; has received grant support from the Agency for Healthcare Research and Quality, Alkermes, AstraZeneca, Cephalon (now Teva), Forest Pharmaceuticals, Eli Lilly and Company, Marriott Foundation, National Institute of Mental Health, Orexigen Therapeutics, Pfizer, Takeda, and Transcept; is an inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders and, along with the patent’s assignee, University of Cincinnati, has received payments from Johnson & Johnson, which has exclusive rights under the patent. Dr Ferreira-Cornwell is a former employee of Shire Development LLC and current employee of GlaxoSmithKline; she holds stock and/or stock options in Shire Development LLC and GlaxoSmithKline. Ms Radewonuk is a former employee of Shire Development LLC and current employee of The Griesser Group; she holds stock and/or stock options in Shire Development LLC and GlaxoSmithKline. Dr Gasior is a former employee of Shire Development LLC and current employee of BTG International; she holds stock and/or stock options in Shire Development LLC and BTG.

Figures

Figure 1.. CONSORT Diagram

aOnly protocol-defined lisdexamfetamine dimesylate responders (those reporting ≤1 binge-eating day per week for the past 4 consecutive weeks [28 days] with a Clinical Global Impressions–Severity score ≤2) were randomized. bThe occurrence of 2 or more binge-eating days per week for 2 consecutive weeks and a 2-point or more CGI-S score increase from randomized withdrawal baseline.

Figure 2.. Time to Relapse Following Randomization for Lisdexamfetamine Responders During the Randomized Withdrawal Phase, Full Analysis Set

Randomized participants taking 1 or more study drug dose during the randomized withdrawal phase and having 1 or more postrandomization Clinical Global Impressions-Severity assessment. Symbols on the plotted lines represent censored participants.