Dasotraline Binge Eating Disorder Extension Study

Study Overview
=================
Brief Summary
-----------------
Binge Eating Disorder Extension Study.

Detailed Description
-----------------
This is a Phase 3, 12 month, multicenter, open-label, flexibly-dosed, safety study in adults with Binge Eating Disorder.

Official Title
-----------------
An Open-label, Flexibly-dosed, Multicenter, Extension Study of Dasotraline to Evaluate Long-term Safety and Tolerability in Adults With Binge-eating Disorder

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

Intervention / Treatment
-----------------
* Drug: Dasotraline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Completion of the treatment period of a dasotraline core study (ie, SEP360 221 or SEP360-321) for the treatment of BED. Subject has agreed to participate by providing written informed consent and is willing and able to comply with the protocol, in the opinion of the investigator. Subject has not taken any medication other than the study drug for the purpose of controlling BED symptoms during the core study. Female subject must have a negative urine pregnancy test at open label (OL) Baseline; females who are post-menopausal (defined as at least 12 months of spontaneous amenorrhea) and those who have undergone hysterectomy or bilateral oophorectomy will be exempted from the pregnancy test. Female subject of childbearing potential and male subject with female partner of childbearing potential must agree to use an effective and medically acceptable form of birth control (see Section 22, Appendix III) throughout the study period. Note: Continued use of an effective and medically acceptable form of birth control is recommended for 30 days after study completion. Subject is judged by the investigator to be suitable for participation in a 12 month clinical trial involving open-label dasotraline treatment. Subject can read well enough to understand the informed consent form and other subject materials. Exclusion Criteria: Subject is considered by the investigator to be at imminent risk of suicide, injury to self or to others, or damage to property. Subject is considered a suicide risk in the investigator's opinion or has any previous history of suicide attempt within the past 12 months. Subject answers yes to suicidal ideation item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C SSRS assessment at OL Baseline. Subjects who answer yes to this question must be referred to the Investigator for follow up evaluation. Subject has a clinically significant abnormality including physical examination, vital signs, ECG, or laboratory tests that the investigator in consultation with the medical monitor considers to be inappropriate to allow participation in the study. Subject has a positive urine drug screen (UDS) or breath alcohol test at OL Baseline. Subject is breastfeeding. Subject is at high risk of non-compliance in the investigator's opinion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 56 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasotraline<br>4, 6, 8 mg flexibly dosed | Drug: Dasotraline<br>* Dasotraline 4, 6, 8 mg flexibly dosed once daily<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Severity of Suicidal Ideation Using the Columbia-suicide Severity Rating Scale (C-SSRS) | Columbia-suicide severity rating scale (C-SSRS) Severity of suicidal ideation is rated on a 6-point scale from 0='No ideation present' to 5='Active ideation with plan and intent'. A score of 4 or 5 on this scale indicates serious suicidal ideation. Suicidal behavior is collected as presence/absence of actual attempts, non-suicidal self-injurious behavior, interrupted attempts, aborted attempts, preparatory acts or behavior, and any suicidal behavior | Baseline to Week 52 | 
| Frequency and Severity of Suicidal Behavior Using the C-SSRS | Columbia-suicide severity rating scale (C-SSRS) Severity of suicidal ideation is rated on a 6-point scale from 0='No ideation present' to 5='Active ideation with plan and intent'. A score of 4 or 5 on this scale indicates serious suicidal ideation. Suicidal behavior is collected as presence/absence of actual attempts, non-suicidal self-injurious behavior, interrupted attempts, aborted attempts, preparatory acts or behavior, and any suicidal behavior | Baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight | Change in body weight | Baseline, Week 52 | 
| Percent Change in Body Weight (kg) | Percent change in body weight (kg) | Baseline, Week 52 | 
| Change in Body Mass Index | Change in Body Mass Index | Baseline, Week 52 | 
| Percent Change in Body Mass Index (kg/m^2) | Percent change in Body Mass Index (kg/m^2) | Baseline, Week 52 | 
| Change in Fasting Lipid Panel, Triglyceride's | Change in fasting lipid panel, Triglyceride's | Baseline, Week 52 | 
| Change in Fasting Lipid Panel , Total Cholesterol | Change in fasting lipid panel , total cholesterol | Baseline, Week 52 | 
| Change in Fasting Lipid Panel , High-density Lipoprotein [HDL] Cholesterol, | Change in fasting lipid panel, high-density lipoprotein [HDL] cholesterol, | Baseline, Week 52 | 
| Change in Fasting Lipid Panel, Low-density Lipoprotein [LDL] Cholesterol) | Change in fasting lipid panel, low-density lipoprotein [LDL] cholesterol) | Baseline, Week 52 | 
| Change in Hemoglobin A1c Levels | Change in hemoglobin A1c levels | Baseline, Week 52 | 
| Change in Fasting Glucose Levels | Change in fasting glucose levels | Baseline, Week 52 | 
| Change in Eating Disorder Examination Questionnaire (EDE Q) Modified Global Score and Subscale Scores (Restraint, Shape, Concern, Weight Concern), and Items 4-6 Scores | Eating Disorder Examination Questionnaire (EDE-Q) Modified global and subscale scores 4 subscale scores (Restraint, Eating Concern, Shape Concern, and Weight Concern) range from 0- 6, where 0 represents absence of the feature and 6 represents an extreme degree. An EDE-Q global score is calculated as average of 4 EDE-Q subscale scores. | Baseline, Week 52 | 
| Change in Eating Disorder Examination Questionnaire (EDE Q) Modified Global Score and Subscale Scores (Restraint, Shape, Concern, Weight Concern), and Items 4-6 Scores | Eating Disorder Examination Questionnaire (EDE-Q) Modified global and subscale scores 4 subscale scores (Restraint, Eating Concern, Shape Concern, and Weight Concern) range from 0- 6, where 0 represents absence of the feature and 6 represents an extreme degree. An EDE-Q global score is calculated as average of 4 EDE-Q subscale scores. Item 4: Over the past 28 days, how many times have you eaten what other people would regard as an unusually large amount of food (given the circumstances)? Item 5: On how many of these times did you have a sense of having lost control over your eating (at the time that you were eating)? | Baseline, Week 52 | 
| Change in Eating Disorder Examination Questionnaire (EDE Q) Modified Global Score and Subscale Scores (Restraint, Shape, Concern, Weight Concern), and Items 4-6 Scores | Eating Disorder Examination Questionnaire (EDE-Q) Modified global and subscale scores 4 subscale scores (Restraint, Eating Concern, Shape Concern, and Weight Concern) range from 0- 6, where 0 represents absence of the feature and 6 represents an extreme degree. An EDE-Q global score is calculated as average of 4 EDE-Q subscale scores. Item 6: Over the past 28 days, on how many DAYS have such episodes of overeating occurred (i.e., you have eaten an unusually large amount of food and have had a sense of loss of control at the time)? | Baseline, Week 52 | 
| Change in Binge Eating Clinical Global Impression-Severity (BE-CGI S) Score | Binge-eating Clinical Global Impression-Severity (BE-CGI-S) The BE-CGI-S is a single value, clinician-rated assessment of illness severity, and 7-point scale with range from 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill subjects. A higher score is associated with greater illness severity. | Baseline, Week 52 | 
| Change in Sheehan Disability Scale (SDS) Total Score and Subscale Scores (School/Work Disability, Social Life Disability, and Family Life Disability) | The Sheehan Disability Scale (SDS) 3 subscales (work/school, social life, home life) are rated on the following scale: 0 = not at all; 1-3 = mildly; 4-6 = moderately; 7-9 =markedly; 10 = extremely. The 3 items can be combined into a single global measure of impairment (SDS total score) that ranges from 0 (unimpaired) to 30 (highly impaired). A higher subscale score and total score are associated with greater illness severity. | Baseline, Week 52 | 
| Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score | Hamilton Anxiety Rating Scale (HAM-A) total score HAM-A total score ranges from 0 to 56. A higher score is associated with a greater degree of anxiety. | Baseline, Week 52 | 
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Montgomery-Asberg Depression Rating Scale (MADRS) total score The MADRS total score ranges from 0 to 60, with higher scores indicating increased depressive symptoms | Baseline, Week 52 | 
| Change in SF-12 Two Component Scores (Physical, Mental Health) | Change in SF-12 two component scores (physical, mental health) for Subjects Continued from Study SEP360-221 The SF-12 is a 12-item self-report questionnaire. Physical Component Summary (PCS) and Mental Component Summary (MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. | Baseline, Week 52 |