SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder

The SPD489-344, Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Dose-optimization Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder

The primary objective of the study is to demonstrate the efficacy of SPD489 compared with placebo in adults (18 55 years of age inclusive) with moderate to severe Binge Eating Disorder at Visit 8 (Weeks 11 and 12) as measured by the number of binge days (defined as days during which at least 1 binge episode occurs) per week as assessed by clinical interview based on subject diary

Study Overview

• Status: Completed
• Conditions: Binge Eating Disorder
• Intervention / Treatment: Drug: SPD489 (Lisdexamfetamine dimesylate); Drug: Placebo

Detailed Description

Not Required

• Study Type: Interventional
• Enrollment (Actual): 390
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Klinische Forschung Berlin-Mitte GmbH
  • Berlin, Germany, 13125
    • Klinische Forschung Berlin Buch GmbH
  • Schwerin, Germany, 19055
    • Klinische Forschung Schwerin GmbH
• United States
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Radiant Research, Inc.
  • California
    • Beverly Hills, California, United States, 90210
      • Southern California Research, LLC
    • La Jolla, California, United States, 92037
      • Scripps Clinical Research Services
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • Oceanside, California, United States, 92056
      • Excel Research, Inc.
    • San Diego, California, United States, 92108
      • PCSD - Feighner Research
  • Colorado
    • Denver, Colorado, United States, 80239
      • Radiant Research, Inc.
  • Florida
    • Bradenton, Florida, United States, 34201
      • Florida Clinical Research Center, LLC
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center, LLC
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, INC.
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research, Inc.
  • Illinois
    • Libertyville, Illinois, United States, 60048
      • Capstone Clinical Research
    • Oak Brook, Illinois, United States, 60523
      • American Medical Research
  • Indiana
    • Newburgh, Indiana, United States, 47630
      • Deaconess Clinic Gateway Health Center
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Clinical Trials Technology, Inc.
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates, Inc.
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • Potomac Grove Clinical Research Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Haverhill, Massachusetts, United States, 01830
      • ActivMed Practices and Research
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical Trials, LLC
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • UMN Medical School, Dept of Psychiatry
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Scientella, LLA
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Robert Lynn Horne, MD, LTD
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Global Medical Inst LLC; Princeton Medical Institute
  • New York
    • Mount Kisco, New York, United States, 10549
      • Bioscience Research, LLC
    • New York, New York, United States, 10023
      • CNS Clinica at the Brain Resource Center
  • Ohio
    • Akron, Ohio, United States, 44311
      • Radiant Research, Inc.
    • Cincinnati, Ohio, United States, 45215
      • Patient Priority Clinical Sites, LLC
    • Mason, Ohio, United States, 45040
      • The Craig and Frances Lindner Center of Hope
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Clinical Trials of America, Inc.
    • Medford, Oregon, United States, 97504
      • Sunstone Medical Research, LLC
    • Portland, Oregon, United States, 97210
      • Oregon Center for Clinical Investigators (OCCI, Inc)
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Lifetree
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Reserach
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Radiant Research, Inc.
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc.
  • Texas
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Plano, Texas, United States, 75093
      • Psychiatric Medical Associates
    • San Antonio, Texas, United States, 78229
      • Radiant Research, Inc.
  • Utah
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute
  • Virginia
    • Herndon, Virginia, United States, 20170
      • Neuroscience, Inc.
  • Washington
    • Seattle, Washington, United States, 98104
      • Summit Research Network (Seattle), LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The subject cannot be enrolled in the study before all of the following inclusion criteria (including test results) are met:

1. Subject is between 18-55 years of age.
2. Subject meets the following Diagnostic and Statistical Manual of Mental Disorders Fourth Edition - Text Revision (DSM-IV-TR) criteria for a diagnosis of BED:
3. Subject has a BED diagnosis.
4. Subject's BED is of at least moderate severity with subjects reporting at least 3 binge eating days per week.
5. Female subjects must have a negative serum B-HCG pregnancy test and a negative urine pregnancy test and agree to comply with any applicable contraceptive requirements.

Exclusion Criteria:

Subjects are excluded from the study if any of the following exclusion criteria are met:

1. Subject has concurrent symptoms of bulimia nervosa or anorexia nervosa.
2. Subject is receiving psychotherapy (eg, supportive psychotherapy, cognitive behavior therapy, interpersonal therapy) or weight loss support (eg, Weight Watchers) for BED.
3. Subject has used psychostimulants to facilitate fasting or dieting as a part of their BED.
4. Subject has a lifetime history of psychosis, mania, hypomania, dementia, or ADHD.
5. Subject is considered a suicide risk, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation.
6. Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems.
7. Subject has a history of moderate or severe hypertension.
8. Subject is female and pregnant or nursing.
9. Subject has had bariatric surgery, lap bands, duodenal stents, or other procedures for weight loss.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Administered once-daily, orally, for up to 12 weeks
Experimental: SPD489 (Lisdexamfetamine dimesylate)	Drug: SPD489 (Lisdexamfetamine dimesylate); 50 or 70 mg administered orally, once-daily for up to 12 weeks; Other Names: Vyvanse, Venvanse, LDX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Number of Binge Days Per Week at Visit 8 Which Spans Weeks 11/12	Binge days defined as days during which at least 1 binge episode occurred. As assessed by clinical interview based on subject binge diary.	Baseline and Visit 8 Which Spans Weeks 11/12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores	Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.	Up to 12 weeks
Percent of Participants With a 4-Week Cessation From Binge Eating	4-week cessation from binge eating is defined as no binge eating episodes for 28 consecutive days prior to the last study visit.	Up to 12 weeks
Percent Change From Baseline in Body Weight (kg) at Week 12		Baseline and week 12
Change From Baseline in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) Total Score at Week 12	The Y-BOCS-BE measures the obsession of binge-eating thoughts and compulsiveness of binge-eating behaviors. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms). Total scores range from 0 to 40. Reduction in total score indicates improvement.	Baseline and week 12
Change From Baseline in Fasting Triglyceride Levels at Up to 12 Weeks		Baseline and up to 12 weeks
Change From Baseline In Fasting Total Cholesterol Levels at Up to 12 Weeks		Baseline and up to 12 weeks
Change From Baseline in Hemoglobin A1c Levels at Up to 12 Weeks		Baseline and up to 12 weeks
Binge Eating Response	Response is based on the reduction in the number of binge eating episodes. Responses were categorized as follows: -1-week Cessation = 100% reduction in binge episodes during the preceding 7 days -Marked Reduction = 99% to 75% reduction during the time since the previous visit -Moderate Reduction = 74% to 50% reduction during the time since the previous visit -Negative to Minimal Reduction = <50% reduction during the time since the previous visit	Up to 12 weeks
Change From Baseline in the Number of Binge Episodes Per Week at Visit 8 Which Spans Weeks 11/12		Baseline and Visit 8 Which Spans Weeks 11/12
Change From Baseline in Eating Inventory Scores at Week 12	There are 36 true/false items, 14 items on a 4-point Likert scale (1=eat rarely to 4=always), and 1 item on a 6-point Likert scale (1=eat whatever you want to 6=constantly limiting food intake). Cognitive Restraint score ranges from 0-21. Hunger score ranges from 0-14. Disinhibition score ranges from 0-16. Higher scores denote higher levels of restrained eating, disinhibited eating and predisposition to hunger.	Baseline and week 12
Change From Baseline in Binge Eating Scale (BES) Score at Week 12	The BES is a self-reported questionnaire containing 16 items designed to assess behavioral, affective, and attitudinal components of the subjective experience of binge eating. Each item is assessed based on 1 of 4 responses, with 1 denoting that a subject has greater control over eating behavior and 4 denoting that a subject had less control over eating behavior. A total score (sum of the 16 items) may range from 16-64. A lower score indicates greater control over eating behavior.	Baseline and week 12
Change From Baseline in Frontal Systems Behavior (FrSBe) Total Score at Up to 12 Weeks	The FrSBe is a 46-item self-rating scale designed to measure the neurobehavioral traits associated with the 3 primary regions of the prefrontal cortex. Subjects were asked to indicate the frequency with which they have engaged in certain behaviors using a rating scale from "1" (almost never) to "5" (almost always). Summary scores were calculated and converted to t-score. A decrease from baseline in FrSBe total score represents improvement.	Baseline and up to 12 weeks
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Mobility	Quality of life was assessed using the EQ-5D-5L, which is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.	Up to 12 weeks
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care		Up to 12 weeks
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities		Up to 12 weeks
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort		Up to 12 weeks
EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression		Up to 12 weeks
Columbia-Suicide Severity Rating Scale (C-SSRS)	C-SSRS is a semi-structured interview that captures the occurence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.	Up to 12 weeks
Change in Amphetamine Cessation Symptom Assessment (ACSA) Total Score From Baseline to Week 12.	ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity. Calculated as Baseline (Day 0) - Week 12 ACSA scores.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• McElroy SL, Hudson J, Ferreira-Cornwell MC, Radewonuk J, Whitaker T, Gasior M. Lisdexamfetamine Dimesylate for Adults with Moderate to Severe Binge Eating Disorder: Results of Two Pivotal Phase 3 Randomized Controlled Trials. Neuropsychopharmacology. 2016 Apr;41(5):1251-60. doi: 10.1038/npp.2015.275. Epub 2015 Sep 9.
• Robertson B, Wu J, Fant RV, Schnoll SH, McElroy SL. Assessment of Amphetamine Withdrawal Symptoms of Lisdexamfetamine Dimesylate Treatment for Adults With Binge-Eating Disorder. Prim Care Companion CNS Disord. 2020 Mar 26;22(2):19m02540. doi: 10.4088/PCC.19m02540.
• Kornstein SG, Bliss C, Kando J, Madhoo M. Clinical Characteristics and Treatment Response to Lisdexamfetamine Dimesylate Versus Placebo in Adults With Binge Eating Disorder: Analysis by Gender and Age. J Clin Psychiatry. 2019 Feb 26;80(2):18m12378. doi: 10.4088/JCP.18m12378.
• Sheehan DV, Gasior M, McElroy SL, Radewonuk J, Herman BK, Hudson J. 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. Innov Clin Neurosci. 2018 Jun 1;15(5-6):22-29.
• Citrome L, Kando JC, Bliss C. Relationships between clinical scales and binge eating days in adults with moderate to severe binge eating disorder in two Phase III studies. Neuropsychiatr Dis Treat. 2018 Feb 15;14:537-546. doi: 10.2147/NDT.S158395. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2012
• Primary Completion (Actual): September 20, 2013
• Study Completion (Actual): September 20, 2013

Study Registration Dates

• First Submitted: October 29, 2012
• First Submitted That Met QC Criteria: October 30, 2012
• First Posted (Estimate): October 31, 2012

Study Record Updates

• Last Update Posted (Actual): July 16, 2021
• Last Update Submitted That Met QC Criteria: June 24, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Hyperphagia; Bulimia; Feeding and Eating Disorders; Binge-Eating Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: SPD489-344; 2012-003310-14 (EudraCT Number)