Effects of Lisdexamfetamine Dimesylate on Functional Impairment Measured on the Sheehan Disability Scale in Adults With Moderate-to-severe Binge Eating Disorder: Results from Two Randomized, Placebo-controlled Trials

Abstract

Objective: In two Phase III, randomized, placebo-controlled trials (NCT01718483 and NCT01718509 at ClinicalTrials.gov), lisdexamfetamine dimesylate (LDX) reduced binge eating days/week in adults with moderate-to-severe binge eating disorder (BED). We describe the effects of LDX (50mg and 70mg) on the Sheehan Disability Scale (SDS; exploratory endpoint) from both studies. Design: The SDS was assessed at baseline, Week 6, and Week 12/early termination. Analyses included mixed-effects models for repeated measures for the examination of SDS total and domain score changes and a generalized estimating equation model to assess dichotomized remission status (remission [total score ≤6] versus nonremission [total score >6]). Results: Least squares (95% confidence interval [CI]) mean treatment differences for SDS total score change from baseline at Week 12 were -2.80 (-3.98, -1.61) in Study 1 and -3.70 (-4.81, -2.58) in Study 2 (both p<0.001). Least squares (95% CI) mean treatment differences across SDS domains favored LDX over placebo in both studies for the change from baseline at Week 12 (work/school: -0.8 [-1.2, -0.4] and -1.1 [-1.5, -0.7], both p<0.001; social life/leisure activities: -1.0 [-1.4, -0.5] and -1.4 [-1.8, -1.0], both p<0.001; and family life/home responsibilities: -1.0 [-1.4, -0.5] and -1.3 [-1.7, -0.9], both p<0.001). Odds ratios (95% CI) for SDS remission versus nonremission favored LDX over placebo at Week 12 (Study 1: 2.39 [1.44, 3.96]; p<0.001 and Study 2: 5.12 [2.80, 9.33]; p<0.001). Conclusion: These findings indicate that LDX treatment is associated with improvement on the SDS in adults with moderate-to-severe BED.

Keywords: Binge eating disorder; Sheehan Disability Scale; disability; functionality; lisdexamfetamine dimesylate.

Conflict of interest statement

FUNDING:This clinical research was supported by the sponsor, Shire Development LLC (Lexington, Massachusetts). The sponsor was involved in the design and conduct of the study, in the collection and analysis of the data, and in the development of the manuscript. The final content and decision to submit this manuscript to Innovations in Clinical Neuroscience was made by the authors. Shire Development LLC provided funding to Complete Healthcare Communications, LLC (CHC) for support in writing and editing this manuscript. DISCLOSURES:Dr. Sheehan is a consultant to Shire Pharmaceuticals and the author of the Sheehan Disability Scale, which measures functional impairment and is the focus of this manuscript; he is an advisory member of the editorial board for Innovations and Clinical Neuroscience. Dr. Gasior is a former employee of Shire and a current employee of BTG International; she holds stock and/or stock options in Shire and BTG International. Ms. Radewonuk is a former employee of Shire and a current employee of The Griesser Group; she holds stock and/or stock options in Shire. Dr. McElroy is a consultant to and has received grant support from Shire. In addition, she is also a consultant to or member of the scientific advisory boards of Alkermes, Bracket, Corcept, F. Hoffmann-LaRoche Ltd, MedAvante, Myriad, Naurex, Novo Nordisk, Sunovion, and Teva. She has also received grant support from the Agency for Healthcare Research & Quality (AHRQ), Alkermes, AstraZeneca, Cephalon (now Teva), Forest, Lilly, Marriott Foundation, the National Institute of Mental Health, Orexigen, Pfizer, Takeda, and Transcept. She is also 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; Cincinnati, Ohio), has received payments from Johnson & Johnson, which has exclusive rights under the patent. Dr. Herman is a former employee of Shire and holds stock and/or stock options in Shire; he is currently an employee of Tris Pharma (Monmouth Junction, New Jersey). Dr. Hudson has received consulting fees and grant support from Shire. In addition, he has received consulting fees from diaMentis, Genentech, and Sunovion as well as grant support from Genentech and Sunovion.

Figures

FIGURE 1.

Mean ± SD SDS total scores during double-blind treatment in (top graph) Study 1 and (bottom graph) Study 2, full analysis set*

FIGURE 2.

Percentage of participants categorized as exhibiting remission* and nonremission* based on SDS total score in (top graph) Study 1 and (bottom graph) Study 2, full analysis set

FIGURE 3.

Mean ± SD SDS domain scores during double-blind treatment in (a–c) Study 1 and (d–f) Study 2, full analysis set*