Forced-dose Titration of SPD489 in Adults With Binge Eating Disorder

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy of SPD489 compared to placebo in the treatment of moderate to severe binge eating disorder as measured by the number of binge days per week

Official Title
-----------------
A Phase 2, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Forced-dose Titration Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults Aged 18-55 Years With Binge Eating Disorder

Conditions
-----------------
Binge Eating Disorder

Intervention / Treatment
-----------------
* Drug: lisdexamfetamine dimesylate (SPD489)
* Drug: lisdexamfetamine dimesylate (SPD489)
* Drug: lisdexamfetamine dimesylate (SPD489)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Subject meets the following Diagnostic and Statistical Manual of Mental Disorders Fourth Edition - Text Revision (DSM-IV-TR) criteria for a diagnosis of binge eating disorder (BED). Binge eating disorder is of at least moderate severity in which subjects report at least 3 binge eating days per week. Subject has a body mass index (BMI) of >24 and <46. Exclusion Subject has concurrent symptoms of bulimia nervosa or anorexia nervosa. Subject is considered a suicide risk or risk to harm others.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPD489 30 mg<br> | Drug: lisdexamfetamine dimesylate (SPD489)<br>* SPD489-30mg capsules taken once daily for up to 11 weeks<br>* Other names: LDX, Vyvanse;|
| Experimental: SPD489 50 mg<br> | Drug: lisdexamfetamine dimesylate (SPD489)<br>* SPD489 50mg capsules taken once-daily for up to 11 weeks<br>* Other names: LDX, Vyvanse;|
| Experimental: SPD489 70 mg<br> | Drug: lisdexamfetamine dimesylate (SPD489)<br>* SPD489 70mg capsule taken once-daily for up to 11 weeks<br>* Other names: LDX, Vyvanse;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo capsule taken once daily for up to 11 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Log Transformed Binge Days Per Week at Week 11 | Binge day is defined as a day during which at least 1 binge episode occurs. | Baseline and week 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Number of Binge Episodes Per Week at Up to 11 Weeks | The number of binge episodes per week as assessed by clinical interview based on subject diary. | Baseline and up to 11 weeks | 
| 1-Week Binge Response, Last Observation Carried Forward (LOCF) | The 1-week binge response was defined as either a 1-week remission (a 100% reduction of binge episodes from baseline [ie, a cessation of binge eating behavior]), or a marked response (75 to <100% reduction in binge episodes from baseline), or a moderate response (50 to <75% reduction in binge episodes from baseline), or a negative/minimal response (<50% reduction in binge episodes from baseline). The 1-week response was determined at the end of the study utilizing a LOCF approach. | Last 7 days on study | 
| 4-Week Binge Response | Subjects are free from binge episodes for 4 weeks. | Last 28 days on study | 
| Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Baseline | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) | Baseline | 
| Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Up to 11 Weeks | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) | up to 11 weeks | 
| Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) at Up to 11 Weeks | 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 11 weeks | 
| Change From Baseline in Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (YBOCS-BE) Total Score at Week 11 | The YBOCS-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. A score of 0-7 is sub-clinical; 8-15 is mild; 16-23 is moderate; 24-31 is severe; and 32-40 is extreme. | Baseline and week 11 | 
| Change From Baseline in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Score at Week 11 | MADRS is a validated, 10-item rating scale with each item being scored on a scale from 0-6 with a total score ranging from 0-60. Lower scores indicate a decreased severity of depression. | Baseline and week 11 | 
| Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Score at Week 11 | The HAM-A is a rating scale developed to quantify the severity of anxiety symptomatology. It consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe) with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity, and 25-30 moderate to severe, and 31-56 severe anxiety. | Baseline and week 11 | 
| Change From Baseline in Eating Inventory Score at Week 11 | 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: cognitive restraint of eating, disinhibition, and hunger. Cognitive restraint of eating consists of 20 items, disinhibition consists of 16 items, and hunger consists of 15 items. Each item scores either 0 or 1 point for a total score of 0-20 for cognitive restraint of eating, 0-16 for disinhibition, and 0-15 for hunger. A higher score is better for cognitive restraint of eating and lower scores are better for disinhibition and hunger. | Baseline and week 11 | 
| Change From Baseline in Binge Eating Scale (BES) Score at Week 11 | The BES is a 16-item self-reported questionnaire that is designed to assess behavioral, affective, and attitudinal components of the subjective experience of binge eating. The items are summed, with possible scores ranging from 0 to 46. A score of 27 or higher indicates severe binge-eating problems, and a score of 17 or lower designates no binge-eating problems. | Baseline and week 11 | 
| Change From Baseline in Barratt Impulsiveness Scale (BIS-11) Total Score at Week 11 | The BIS-11 is a self-reported 30-item questionnaire that measures impulsiveness using a 4-point Likert scale (rarely/never = 1, occasionally = 2, often = 3, almost always/always = 4). A Total Impulsivity score is calculated by summing the scores for each item. Possible scores range from 30 - 120. Higher scores indicate increased impulsiveness. | Baseline and week 11 | 
| Change From Baseline in Short Form-12 Health Survey (SF-12) Score at Week 11 | The SF-12 is a 12-item self-report questionnaire that is a subset of the SF-36 Health Survey. The survey captures physical and mental health. There are 8 subscales. Four of the subscales has one-item each; the other 4 have two-items each. For each subscale, a mean value was first computed and transformed to a position on a scale ranging from 0-100 (Z-transformation). The aggregate total scores are then transformed into a mean value ranging from 0 (lowest level of health) to 100 (highest level of health). | Baseline and week 11 |