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

Study Overview
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Brief Summary
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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

Official Title
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The SPD489-343, 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

Conditions
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Binge Eating Disorder

Intervention / Treatment
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* Drug: SPD489 (Lisdexamfetamine dimesylate)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria - Subject is between 18-55 years of age. Subject meets the following DSM-IV-TR 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. Subject's BED is of at least moderate severity with subjects reporting at least 3 binge eating days per week for the 14 days prior to the Baseline Visit (Visit 0) as documented in the subject's binge diary. A binge day is a day during which at least 1 binge eating episode occurs. Female subjects must have a negative serum B HCG pregnancy test and a negative urine pregnancy test. Exclusion Criteria- Subject has concurrent symptoms of bulimia nervosa or anorexia nervosa. Subject is receiving psychotherapy (eg, supportive psychotherapy, cognitive behavior therapy, interpersonal therapy) or weight loss support (eg, Weight Watchers) for BED within 3 months. Subject has used psychostimulants to facilitate fasting or dieting as a part of their BED within 6 months. Subject has a lifetime history of psychosis, mania, hypomania, dementia, or ADHD. Subject is considered a suicide risk in the opinion of the investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the investigator. 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. Subject has recently initiated treatment with a lipid-lowering medication (within the past 3 months). Subject has a history of moderate or severe hypertension. Subject is female and pregnant or nursing. Subjects who have had bariatric surgery, lap bands, duodenal stents, or other procedures for weight loss.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 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 | 
| Percentage 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 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 Week 12/Early termination (ET) | 
| Change From Baseline In Fasting Total Cholesterol Levels at Up to 12 Weeks |  | Baseline and Week 12/ET | 
| Change From Baseline in Hemoglobin A1c Levels at Up to 12 Weeks |  | Baseline and Week 12/ET | 
| Binge Eating Response | Response is based on the reduction in the number of binge eating episodes. Percentage of participants with response was reported. 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. | Week 12/ET | 
| Change From Baseline in the Number of Binge Episodes Per Week at Visit 8 (Weeks 11-12) |  | Baseline and Visit 8 (Weeks 11-12) | 
| Change From Baseline in Eating Inventory Scores at Week 12 | The Eating Inventory also known as the Three-Factor Eating Questionnaire is a 51-item self-reported questionnaire intended to assess 3 dimensions of eating behavior. 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 participant has greater control over eating behavior and 4 denoting that a participant 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 Week 12 | 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. Participants 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 Week 12 | 
| 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. Percentage of participants with various mobility conditions were reported. | Up to 12 weeks | 
| EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Self-Care | 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. Percentage of participants with various self-care conditions were reported. | Up to 12 weeks | 
| EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Usual Activities | 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. Percentage of participants with various usual activities conditions were reported. | Up to 12 weeks | 
| EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Pain/Discomfort | 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. Percentage of participants with various pain/discomfort conditions were reported. | Up to 12 weeks | 
| EuroQoL Group 5-Dimension 5-Level Self-Report (EQ-5D-5L): Anxiety/Depression | 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. Percentage of participants with various anxiety/depression conditions were reported. | Up to 12 weeks | 
| Columbia-Suicide Severity Rating Scale (C-SSRS) | C-SSRS is a semi-structured interview that captures the occurrence, 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. Number of participants with suicidal ideation and suicidal behavior were reported. | Up to 12 weeks | 
| Amphetamine Cessation Symptom Assessment (ACSA) Total Score | 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. | Up to 12 weeks |