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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 (?21, 40.37; P?

SUBMITTER: Hudson JI

PROVIDER: S-EPMC5710231 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Hudson James I JI McElroy Susan L SL Ferreira-Cornwell M Celeste MC Radewonuk Jana J Gasior Maria M

JAMA psychiatry 20170901 9

<h4>Importance</h4>The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important.<h4>Objective</h4>To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder.<h4>Design, setting, and participants</h4>A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites ...[more]

PMID: 28700805

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Project description:BackgroundPreliminary placebo-controlled evidence paved the ground to the US Food and Drug Administration approval extension of lisdexamfetamine for the treatment of moderate-to-severe binge eating disorder (BED) in adults.ObjectivesTo provide a preliminary qualitative and quantitative synthesis of the placebo-controlled, randomized clinical trials (RCTs) considering the efficacy and tolerability of lisdexamfetamine in the acute and/or maintenance treatment of moderate-to-severe BED in adults.MethodsA preliminary, yet comprehensive, systematic review was performed by accessing a broad range of resources providing publicly available data about lisdexamfetamine at the time of inquiry (March 2016). Study eligibility criteria, participants, and interventions were considered focusing on major clinical and functional outcomes of either efficacy or tolerability of lisdexamfetamine in the treatment of moderate-to-severe BED in adults.ResultsMeta-analysis of data pooled from three acute RCTs significantly favored lisdexamfetamine over placebo in the reduction of binge eating days/week, Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating total score, weight, response, and remission rates (all, P≤0.01). In contrast, discontinuation rates due to treatment-emergent adverse events were significantly higher among patients in receipt of lisdexamfetamine (relative risk 2.19, P=0.04) versus placebo.LimitationsPublication, selection, performance, attrition, reporting, sponsorship, and "diagnostic shift" biases. Lack of inclusion of adverse event effects other than those requiring discontinuation of the trial(s), as well as lack of information about clinically relevant psychiatric or other medical comorbidities, limits the overall generalizability of pooled results.ConclusionAcross the included acute phase RCTs, lisdexamfetamine (at 30, 50, or 70 mg/day) led to significant reduction in a number of clinically relevant outcomes compared to placebo. Moreover, safety concerns related to adverse events, high discontinuation rates, and the need for additional long-term maintenance of RCTs solicit careful monitoring of the drug in terms of overall safety and tolerability by further RCTs.

Project description:ObjectivesIn two Phase III studies, lisdexamfetamine dimesylate (LDX) reduced binge eating (BE) days/week in adults with moderate to severe binge eating disorder (BED) and was associated with improvement based on the Clinical Global Impressions-Improvement (CGI-I) scale. In this study, post hoc analyses examined the relationships between clinical observations and clinical rating scales in individuals with BED.Clinical trial registrationNCT01718483 (ClinicalTrials.gov/ct2/show/NCT01718483); NCT01718509 (ClinicalTrials.gov/ct2/show/NCT01718509).MethodsTwo 12-week, double-blind, placebo-controlled studies randomized (1:1) adults meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, BED criteria and with protocol-defined moderate to severe BED (study 1, N=383; study 2, N=390) to placebo or dose-optimized LDX (50 or 70 mg). Assessments included the number of BE days/week, CGI-Severity (CGI-S) and CGI-I scores, and Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (Y-BOCS-BE) total scores. For these post hoc analyses, data were pooled across studies and treatment arms. Statistical assessments included Spearman correlations and equipercentile linking analyses (ELA). Reported P-values are nominal (descriptive and not adjusted for multiplicity).ResultsAt baseline, nominally significant correlations with CGI-S scores were reported for BE days/week (r=0.374; P<0.0001) and Y-BOCS-BE total scores (r=0.319; P<0.0001). Baseline ELA for CGI-S further characterized this relationship: a CGI-S score of 4 (moderately ill) corresponding to 3.504 BE days/week and a Y-BOCS-BE total score of 18.6. Nominally significant correlations with CGI-I scores were reported for changes from baseline at study endpoint for BE days/week (r=0.647; P<0.0001) and Y-BOCS-BE total scores (r=0.741; P<0.0001). ELA for CGI-I scores at study endpoint showed that a CGI-I score of 1 (very much improved) corresponds to a reduction from baseline of 4.504 BE days/week and 19.4 points for Y-BOCS-BE total score.ConclusionThese post hoc analyses suggest that indices of global disease severity and improvement positively correlate with BE behavior and with obsessive and compulsive features of BED, measured by the Y-BOCS-BE, supporting the clinical relevance of BED treatment outcomes.

Dataset Information

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

Publications

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

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