Evaluate the Maintenance of Efficacy of SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder

A Phase 3, Multicenter, Double-blind, Placebo-controlled, Randomized-withdrawal Study to Evaluate the Maintenance of Efficacy of SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder

To evaluate maintenance of efficacy based on time to relapse between SPD489 (50 or 70mg) and placebo, 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 and Clinical Global Impression - Severity (CGI-S) scores for patients who responded to SPD489 by the end of the Open-label Treatment Phase.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 418
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Mississauga, Ontario, Canada, L5< 4N4
      • Anxiety and Mood Disorder Center
  • Quebec
    • Pointe Claire, Quebec, Canada, H9R 4S3
      • Manna Research
• Germany
  • Berlin, Germany, 10117
    • Klinische Forschung Berlin-Mitte GmbH
  • Berlin, Germany, 10629
    • EMOVIS GmbH - Klinische Forschung
  • Dresden, Germany, 01069
    • Klinische Forschung Dresden GmbH
  • Hannover, Germany, 30159
    • Klinische Forschung Hannover-Mitte GmbH
  • Schwerin, Germany, 19055
    • Forschung Schwerin GmbH, Friedrichstrasse 1
  • Westerstede, Germany, 26655
    • Studienzentrum Nordwest
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
  • Madrid, Spain, 28822
    • Hospital del Henares
• Sweden
  • Malmo, Sweden, 211 52
    • Lakarmottagningen Ekdahl & Kronberg
  • Stockholm, Sweden, 114 86
    • Sofiahemmet
  • Stockholm, Sweden, 118 50
    • Stockholm Center for Eating Disorders
• United States
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research, INC
    • Leesburg, Florida, United States, 34748
      • Compass Research LLC North Clinic
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center, LLC
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc
    • 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
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Goldpoint Clinical Research
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Clinical Trials Technology, Inc
    • Wichita, Kansas, United States, 67226
      • Cypress Medical Research Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates, Inc
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical Trials, LLC
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • HBSA-Pacific Institute for Research & Evaluation
  • New York
    • Brooklyn, New York, United States, 11214
      • Brooklyn Medical Institute
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Community Research
    • Cincinnati, Ohio, United States, 45215
      • Patient Priority Clinical Sites, LLC
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
    • Mason, Ohio, United States, 45040
      • Linder Center of Hope
  • Oregon
    • Portland, Oregon, United States, 97214
      • Oregon Center For Clinical Investigations, Inc (Occi, Inc)
    • Salem, Oregon, United States, 97301
      • Oregon Center For Clinical Investigations, Inc (Occi, Inc)
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Radiant Research, Inc
    • Greer, South Carolina, United States, 29650
      • Radiant Research, Inc
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solution, Inc
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Clinical Trials, LP
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc
    • Plano, Texas, United States, 75093
      • Research Across America
    • San Antonio, Texas, United States, 78229
      • Radiant Research, Inc
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • 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:

1. Subject is between 18-55 years of age, inclusive.

2. Subject meets the following criteria for a diagnosis of BED:

   • Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following: eating, in a discrete period of time (eg, within a 2-hour period) an amount of food that is definitely larger than most people would eat in a similar period of time under similar conditions, and a sense of lack of control over the eating (eg, a feeling that one cannot stop eating or control what or how much one is eating).
   • The binge eating episodes are associated with at least 3 of the following: eating much more rapidly than normal; eating until uncomfortably full; eating large amounts of food when not feeling physically hungry; eating alone because of being embarrassed by how much one is eating; feeling disgusted with oneself, depressed, or feeling very guilty after overeating.
   • Marked distress regarding binge eating.
   • The binge eating occurs, on average, at least 2 days a week for 6 months.
   • The episodes of binge eating do not occur exclusively during the course of bulimia nervosa or anorexia nervosa.
3. Subject is consistently able to swallow a capsule.

Exclusion Criteria:

1. Subject has current diagnosis of bulimia nervosa or anorexia nervosa.
2. Subject is receiving psychotherapy or weight loss support within the past 3 months.
3. Subject has used psychostimulants to facilitate fasting or dieting within the past 6 months.
4. Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease.
5. Subject has abnormal thyroid function.
6. Subject initiated treatment with a lipid lowering medication within the past 3 months.
7. Subject has a history of moderate or severe hypertension.
8. Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder.
9. Subject has glaucoma.
10. Subject is female and pregnant or nursing.
11. Subjects who have 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: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lisdexamfetamine dimesylate; Administer one capsule (50 or 70 mg) orally daily at approximately 7:00 AM.	Drug: Lisdexamfetamine dimesylate; SDP489 30, 50, or 70mg capsule once per day (open-label and double-blind periods); Other Names: LDX; SPD489
Placebo Comparator: Placebo; Administer one capsule orally daily at approximately 7:00 AM.	Other: Placebo; Placebo capsule once per day (double-blind period)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Relapse From Date of Randomization to Endpoint of The Randomized-withdrawal Period	Relapse status was assessed during the double-blind treatment phase and was defined as having 2 or more binge days per week for 2 consecutive weeks (14 consecutive days) prior to any visit and having an increase in Clinical Global Impressions-Severity (CGI-S) score of 2 or more points compared to the randomized-withdrawal baseline (date of relapse - date of randomization). Binge eating information was captured via a self-report paper diary. The binge diary captured the number of binges per day, total hours per day spent binging, type of binge (at mealtime or at another time other than mealtime), and a description of the binge (amounts and types of foods). Binge frequency was reviewed by the clinician with the subject to confirm reported binge episodes per day. The CGI-S was performed to rate the severity of a subject's condition using a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill).	Visit 21 (26 weeks after randomization [Week 38] or Early Termination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Randomized-Withdrawal Baseline in The Number of Binge- Eating Days Per Week During The Randomized-withdrawal Period	A binge day was defined as days during which at least 1 binge episode occurred. As assessed by clinical interview based on subject binge diary. Binge eating information was captured via a self-report paper diary. The binge diary captured the number of binges per day, total hours per day spent binging, type of binge (at mealtime or at another time other than mealtime), and a description of the binge (amounts and types of foods). Binge frequency was reviewed by the clinician with the subject to confirm reported binge episodes per day. A negative change from Baseline indicates that binge-related behavior decreased. The randomized -withdrawal-baseline was defined as the weekly average number of binge days for the 14 days prior to the Randomization Visit (Visit 8).	Randomized--withdrawal baseline (Visit 8; 12 weeks after start of open- label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38])
Percent of Participants Within Each Category of The Clinical Global Impression-Severity of Illness (CGI-S) Scale at Endpoint of The Randomized-withdrawal Period	The CGI-S permits a global evaluation of a subject's condition and severity of symptoms. The CGI-S was performed to rate the severity of a subject's condition based on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill).	Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Change From Randomized-Withdrawal Baseline in The Total Score of The Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) During The Randomized-withdrawal Period	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). The scale includes questions regarding the amount of time spent on obsessions, impairment or distress experienced, and resistance and control over these thoughts. The same types of questions were asked about compulsions (ie, time spent, interference, etc.).Total scores range from 0 to 40. A total score of 0-7 is sub-clinical, 8-15 is mild, 16-23 is moderate, 24-31 is severe, and 32-40 is extreme. A decrease from baseline in Y-BOCS-BE Total Score represents an improvement in obsession with binge-eating thoughts or compulsiveness of binge-eating behaviors.	Randomized-withdrawal baseline (Visit 8; 12 weeks after start of open-label treatment [Week 12]), Visit 21 (26 weeks after randomization [Week 38])
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Mobility at Endpoint of The Open-label Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Percent of Participants Within Each Category of The EuroQuol Group 5--Dimension 5--Level Self--Report Questionnaire (EQ--5D--5L) For Mobility at Endpoint of The Randomized-withdrawal Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Open-label Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Self Care at Endpoint of The Randomized-withdrawal Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Open-label Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Usual Activities at Endpoint of The Randomized-withdrawal Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Open-label Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Pain and Discomfort at Endpoint of The Randomized-withdrawal Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Open-label Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 8 (12 weeks after start of open-label treatment [Week 12] or Early Termination)
Percent of Participants Within Each Category of The EuroQuol Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) For Anxiety And Depression at Endpoint of The Randomized-withdrawal Period	The EuroQoL Group 5-Dimension 5-Level Self-Report Questionnaire (EQ-5D-5L) is a health-related quality of life (QoL) measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as well as current overall health. 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. Each dimension is represented by a single item with 5 levels of responses, from poor health to good health.	Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Open-label Period	The C-SSRS is a semistructured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. 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 interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answer to the first 2 ideation questions was "yes," the clinician asked questions 3-5. Active suicidal ideation included any participant who answered "yes" to questions 2-5. If the answers to ideation questions 1 and 2 were "No," then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide.	Visit 8 (12 weeks after start of open-label treatment [Week 12])
Number of Participants With a Positive Response on The Columbia Suicide Severity Rating Scale (C-SSRS) at Endpoint of The Randomized-withdrawal Period	The C-SSRS is a semistructured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. 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 interview was initiated with 5 (yes/no) questions, presented in ascending order of severity, about suicidal ideation. The most severe type of ideation was rated for frequency, duration, controllability, deterrents, and reason. If the answer to the first 2 ideation questions was "yes," the clinician asked questions 3-5. Active suicidal ideation included any participant who answered "yes" to questions 2-5. If the answers to ideation questions 1 and 2 were "No," then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, interrupted attempt, aborted attempt, preparatory acts or behaviors, and completed suicide.	Visit 21 (26 weeks after randomization [Week 38] or Early Termination)
Total Scores For The Amphetamine Cessation Symptom Assessment (ACSA) Scale During Follow-up	The ACSA was used in this study to assess potential withdrawal symptoms associated with chronic use of SPD489. The ACSA is a self-completed scale used to assess withdrawal symptoms. The scale has 16 symptom items rated on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The ACSA total score ranges from 0-64, where a higher score indicates greater withdrawal symptom severity.	Visit 21 (26 weeks after randomization [Week 38] or Early Termination) and Visit 22 (7 days post last dose)

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.
• Hudson JI, McElroy SL, Ferreira-Cornwell MC, Radewonuk J, Gasior M. Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2017 Sep 1;74(9):903-910. doi: 10.1001/jamapsychiatry.2017.1889.

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2014
• Primary Completion (Actual): April 8, 2015
• Study Completion (Actual): April 8, 2015

Study Registration Dates

• First Submitted: December 6, 2013
• First Submitted That Met QC Criteria: December 6, 2013
• First Posted (Estimate): December 11, 2013

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 9, 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: SPD489-346; 2012-004457-88 (EudraCT Number)