Relationships between clinical scales and binge eating days in adults with moderate to severe binge eating disorder in two Phase III studies

Abstract

Objectives: In 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 registration: NCT01718483 (ClinicalTrials.gov/ct2/show/NCT01718483); NCT01718509 (ClinicalTrials.gov/ct2/show/NCT01718509).

Methods: Two 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).

Results: At 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.

Conclusion: These 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.

Keywords: Clinical Global Impressions scale; Yale-Brown Obsessive Compulsive Scale modified for Binge Eating; binge eating days; binge eating disorder; clinical rating scales; lisdexamfetamine dimesylate.

Conflict of interest statement

Disclosure Dr Citrome has served as a consultant for Acadia, Alkermes, Allergan, Eli Lilly, Forum, Intra-Cellular Therapeutics, Janssen, Lundbeck, Merck, Neurocrine, Noven, Otsuka, Pfizer, Reviva, Shire, Sunovion, Takeda, Teva, and Vanda and as a speaker for Acadia, Alkermes, Allergan, Janssen, Lundbeck, Merck, Neurocrine Biosciences, Inc., Otsuka, Pfizer, Shire, Sunovion, Takeda, Teva, and Vanda. Dr Kando is a former employee of Shire and holds stock and/or stock options in Shire; she is currently an employee of Adamas Pharmaceuticals (Emeryville, CA). Dr Bliss is an employee of Shire and holds stock and/or stock options in Shire. The authors report no other conflicts of interest in this work.

Figures

Figure 1

Equipercentile linking functionsa at baseline (A and B) and for change from baseline (C and D), pooled full analysis set. Notes:aThe equipercentile linking function requires that both variables be continuous. To apply this method, scores for CGI-S, CGI-I, and Y-BOCS-BE were considered piecewise continuous ranging from X −0.5 to X +0.5, and scores for binge eating days/week were considered piecewise continuous ranging from X −0.005 to X +0.005. Therefore, all values are understood to encompass a range. Abbreviations: BE, binge eating; CGI-I, Clinical Global Impressions–Improvement; CGI-S, Clinical Global Impressions–Severity; ET, early termination; LDX, lisdexamfetamine dimesylate; PBO, placebo; Y-BOCS-BE, Yale-Brown Obsessive Compulsive Scale modified for Binge Eating.