A Study to Evaluate a Drug (Dasotraline) on the Safety, Effectiveness and How Well the Body Tolerates it, in Adults With Moderate to Severe Binge Eating Disorder

A 12-week, Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed-dosed, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Dasotraline in Adults With Moderate to Severe Binge Eating Disorder

A study to evaluate a drug (dasotraline) on the safety, effectiveness and how well the body tolerates it, in adults with moderate to severe binge eating disorder

This is a randomized, double-blind, parallel-group, multicenter, outpatient study evaluating the efficacy and safety of 2 doses of dasotraline (4 and 6 mg/day) versus placebo over a 12-week treatment period in adults with BED. This study is projected to randomize approximately 480 subjects to 3 treatment groups in a 1:1:1 ratio (4 mg/day dasotraline, 6 mg/day dasotraline, and placebo).

Subjects randomized to placebo will receive placebo for the duration of the treatment period.

Subjects randomized to 4 mg/day dasotraline will receive 4 mg/day for the duration of the treatment period.

Subjects randomized to 6 mg/day dasotraline will be dosed with 4 mg/day dasotraline for the first 2 weeks of the treatment period and will be increased to 6 mg/day at Week 2.

If, in the judgment of the Investigator, the subject does not tolerate the assigned dose, he or she will be discontinued from the study.

The study will consist of 3 periods: Screening (up to 3 weeks), 12-weeks of treatment, and a 3-week study drug withdrawal period. Subjects who complete the 12-week double-blind treatment period in this study may be eligible to enroll and continue treatment for an additional 12 months in an open-label extension study (Study SEP360-322). Subjects who do not enter the extension study will complete the study drug withdrawal period in this study.

Inclusion Criteria:

- 1. Male or female subject between 18-55 years of age, inclusive, at time of informed consent.

2. Subject meets the following DSM-5 criteria for a diagnosis of BED. An episode of binge eating is characterized by both:

• Eating an amount of food larger than what most people would eat, in a discrete period of time (eg, 2 hours)
• Sense of lack of control over eating episode

Binge eating episodes are associated with ≥ 3 of the following:

• Eating much more rapidly than normal

• Eating until uncomfortably full

• Eating large amounts when not feeling hungry

• Eating alone because of embarrassment

• Feeling disgusted with oneself, guilty afterward Binge eating episodes are also associated with marked distress regarding the episode and not associated with recurrent use of compensatory behavior (eg, bulimia nervosa). Note: A subject using compensatory behavior less than 1 time every 2 weeks over the 3 months prior to screening may be permitted to enroll in the study.

  3. Diagnosis is confirmed based on the Structured Clinical Interview for DSM-IV Axis I Disorders, Module H (SCID-I Module H), clinician review of subject diaries, and the EDE-Q.

  4. Subject has a BED diagnosis or is diagnosed at screening and has a history of at least 2 binge eating days a week for at least 6 months prior to screening.

  5. Subject's BED is of at least moderate severity with subject reporting at least 3 binge eating days for each of the 2 weeks prior to baseline as documented in the subject's binge diary. A binge eating day is defined as having at least one binge eating episode 6. Subject has a BE- CGI-S score ≥ 4 at screening and baseline. 7. Subject has a negative breath alcohol test and a negative UDS for any illicit drug.

  8. Female subject must have a negative serum pregnancy test at screening; 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.

  9. 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 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.

  10. Subject must be able to comply with study drug administration and adhere to protocol requirements including all study assessments.

  11. Subject can read well enough to understand the informed consent form and other subject materials

Exclusion Criteria:

1. Subject has BMI of 18 kg/m2or less, or greater than 45 kg/m2.
2. Subject has a lifetime history or current symptoms consistent with bulimia nervosa or anorexia nervosa.
3. Subject has started psychotherapy (eg, supportive psychotherapy, cognitive behavior therapy, interpersonal therapy) within 3 months prior to screening. Note: Subjects receiving stable ongoing psychotherapy for longer than 3 months are permitted to enroll.
4. Subject has participated in a formal weight loss program (eg, Weight Watchers®) within 3 months prior to screening.
5. Subject has used a psychostimulant or mood stabilizer within the 3 months prior to screening.
6. Subject has used any medications for the treatment of binge eating, other eating disorders, obesity, or weight gain or any other medication that could result in weight gain or weight loss including over-the-counter and herbal products within the 3 months prior to screening.
7. Subject has received lisdexamfetamine dimesylate (Vyvanse®) for any reason, including but not limited to participation in any Phase 2 or 3 trial.
8. Subject has a lifetime history of psychotic disorder, bipolar disorder, hypomania, dementia, or ADHD as defined by the DSM-5 criteria.
9. Subject has a history of moderate to severe depression based on Investigator's judgment within the 6 months prior to screening or is currently taking or has taken any medication for depression during the 3 months prior to screening.
10. Subject has MADRS score ≥ 18 at screening and Baseline visit.
11. Subject has a history of substance use disorder including alcohol use disorder (excluding nicotine and caffeine) within the 12 months prior to screening, as defined by the DSM-5 criteria.
12. Subject is considered a suicide risk in the investigator's opinion or has any previous history of suicide attempt within the past 12 months.
13. 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 screening (in the past month). Subjects who answer "yes" to this question must be referred to the Investigator for follow-up evaluation.
14. Subject has type I diabetes mellitus or insulin-dependent diabetes mellitus.
15. Subject with type II diabetes mellitus, has hemoglobin A1c ≥ 6.5% at screening, or has initiated treatment with or changed the dose of a glucose-lowering agent within 3 months prior to screening.
16. Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, documented heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems.
17. Subject has initiated treatment with or changed the dose of a lipid-lowering medication within the 3 months prior to screening.
18. Subject has a history of moderate or severe hypertension that in the Investigator's opinion has not been medically stable or has required a change in dosage and/or medication during the 3 months prior to screening.
19. Subject has a history of focal or diffuse brain disorder including but not limited to epilepsy, seizures (except childhood febrile seizures),stroke, benign or malignant tumors, or head trauma with loss of consciousness lasting more than 5 minutes; unexplained syncope or other unexplained blackouts (except single incident); or a history of clinically significant repeated head-traumas without loss of consciousness.
20. Subject has had polycystic ovarian syndrome (PCOS) in the previous 12 months, even if no treatment was provided.
21. Subject is female and pregnant or nursing.
22. Subject has had major bariatric surgery, eg, gastric jejunal bypass,Roux-en-Y gastric bypass, sleeve gastrectomy, duodenal switch with biliopancreatic diversion for weight loss at any time.
23. Minor bariatric surgey (eg, lap bands) within 3 years of screening. Note: Surgeries for cosmetic reasons are not exclusionary but should be discussed with the medical monitor.
24. Subject has a history of positive test for either Hepatitis B surface antigen or Hepatitis C antibody, and has liver function test results at screening above the upper limit of normal (ULN) for the reference laboratory.
25. Subject without a history of positive test for Hepatitis B surface antigen or Hepatitis C antibody has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥ 2 times the ULN at screening.
26. Subject has a blood urea nitrogen (BUN) value ≥ 1.5 times the ULN for the reference range, serum creatinine > 1.5 times the ULN for the reference range, fasting blood glucose ≥ 126 mg/dL (7.0 mmol/L), or hemoglobin A1c ≥ 6.5% at screening.
27. Subject is known to have tested positive for human immunodeficiency virus (HIV).
28. Subject has a clinically significant abnormality on screening evaluation including physical examination, vital signs, ECG, or laboratory tests that the Investigator considers to be inappropriate to allow participation in the study.
29. The subject's screening ECG shows a corrected QT interval using Fridericia's formula (QTcF) of ≥ 450 msec for male subjects or ≥ 470 msec for female subjects. Eligibility will be based on the core laboratory ECG interpretation report.
30. Subject has any life-time history of abuse or diversion of stimulants.
31. Subject has a history of allergic reaction or has a known or suspected sensitivity to any substance that is contained in the study drug formulation.
32. Subject who in the opinion of the Sponsor and Investigator has any other psychiatric or medical condition or disorder or any other psychosocial or work-related issue not previously listed that could interfere with the diagnosis of BED at screening or subsequent evaluations during the course of the study.
33. Subject who may experience or who is currently experiencing significant psychosocial or environmental stressors (eg, loss of employment, loss of housing, financial hardship, divorce) that could impede their ability to adhere to protocol requirements, as judged by the Investigator.
34. Subject is currently participating in or has participated in any clinical trial within the last 90 days or has participated in more than 2 clinical trials within the past year. This includes studies using marketed compounds or devices.
35. Subject has previously been enrolled in a clinical trial of dasotraline (SEP-225289).
36. Subject is an investigational site staff member or the relative of an investigational site staff member.
37. Subject has started a new physical training/exercise program for the purpose of managing his or her weight or binge eating within 3 months prior to screening. Note: Subjects participating in a stable physical training/exercise program for longer than 3 months are permitted to enroll.
38. Subject has a history of malignancy within 5 years prior to the Screening visit, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. History of pituitary tumor, whether benign or malignant, is exclusionary.