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

Detailed Description
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Not Required

Official Title
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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

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: The subject cannot be enrolled in the study before all of the following inclusion criteria (including test results) are met: Subject is between 18-55 years of age. Subject meets the following Diagnostic and Statistical Manual of Mental Disorders Fourth Edition - Text Revision (DSM-IV-TR) criteria for a diagnosis of BED: Subject has a BED diagnosis. Subject's BED is of at least moderate severity with subjects reporting at least 3 binge eating days per week. 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: 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. Subject has used psychostimulants to facilitate fasting or dieting as a part of their BED. Subject has a lifetime history of psychosis, mania, hypomania, dementia, or ADHD. Subject is considered a suicide risk, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. 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 a history of moderate or severe hypertension. Subject is female and pregnant or nursing. Subject has 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 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 |