Lisdexamfetamine in Binge Eating Disorder (BED): fMRI Effects

12-week, open-label LDX trial for BED including fMRI assessments to test the following
specific predictions:

1. At baseline, patients with BED will show greater ventral prefrontal, striatal, and
amygdala brain activation to high-calorie food pictures (reward) than matched healthy
comparison subjects.

2. After 12 weeks of LDX treatment, BED will exhibit reduced ventral prefrontal, striatal
and amygdala brain activation to food cues compared to baseline.

3. BED patients who display cessation of binge eating and those who demonstrate clinical
improvement after 12 weeks of LDX treatment will show greater reductions in ventral
prefrontal, striatal, and amygdala brain activation to food pictures than patients who
do not stop binge eating and those who do not improve, respectively.

Inclusion Criteria: Criteria for entering this study will include all of the following:

1. Subjects will meet the DSM-IV-TR criteria for a diagnosis of binge eating disorder
(BED) for at least the last 6 months.

2. Subjects will report at least 3 binge eating (BE) days per week for the two weeks
prior to LDX initiation prospectively documented in take-home binge diaries.

3. Women, through the ages of 18 and 55 years, inclusive.

4. Willingness to receive open-label LDX treatment for 12 weeks.

5. Willingness to receive an fMRI before and after 12 weeks of LDX treatment.

Exclusion Criteria:

Criteria for exclusion from this study will include all of the following:

1. Have concurrent symptoms of bulimia nervosa or anorexia nervosa.

2. Women who are pregnant, lactating, or of childbearing potential who are not using
adequate contraceptive measures. The following are considered to be adequate methods
of birth control: 1. intrauterine device (IUD); 2. barrier protection; 3. a
contraceptive implantation system (Norplant); 4. oral contraceptive pills; 5. a
surgically sterile patient; and 6. abstinence. All female subjects will have a
negative pregnancy test prior to randomization.

3. Subjects who are displaying suicidal ideation on the Columbia-Suicide Severity Scale
(C-SSRS) (21), or a suicide attempt within the last year as defined by the C-SSRS, or
homicidality.

4. Subjects who are receiving a psychological (e.g., supportive psychotherapy, cognitive
behavior therapy, interpersonal therapy) or weight loss (e.g., Weight Watchers)
intervention for BED that was begun within the 3 months before study entry. Subjects
who are receiving psychotherapy that was initiated prior to 3 months of the beginning
of the study will be allowed to continue to receive their psychotherapy during the
trial only if they agree to not make any changes to the frequency or nature of their
psychotherapy during the course of the drug trial.

5. A DSM-IV-TR diagnosis of substance abuse or dependence (except nicotine abuse or
dependence) within the 6 months prior to randomization.

6. Subjects who have used psychostimulants to facilitate fasting or dieting as a part of
their eating disorder within the past 6 months; patients who have misused
psychostimulants within the past 6 months; and patients who have a drug screen at the
screening visit positive for psychostimulants.

7. A lifetime DSM-IV-TR history of ADHD, psychosis, mania or hypomania, or dementia.

8. History of any psychiatric disorder which might interfere with a diagnostic
assessment, treatment, or compliance, or a current Montgomery Asberg Depression Scale
(MADRS) (22) score ≥ 18.

9. Clinically unstable medical disease, including cardiovascular, hepatic, renal,
gastrointestinal, pulmonary, metabolic, endocrine or other systemic disease;
clinically significant abnormalities on physical exam; or clinically significant
laboratory abnormalities. Subjects should be biochemically euthyroid to enter the
study.

10. Have a history of a structural cardiac abnormality, cardiomyopathy, serious heart
rhythm abnormality, coronary artery disease, stroke, or other serious cardiovascular
problem.

11. History of seizures, including clinically significant febrile seizures in childhood.

12. Have uncontrolled hypertension (>160/100) or tachycardia (heart rate >110). m. Have
an ECG with significant arrhythmias or conduction abnormalities, which in the opinion
of the physician investigator preclude study participation.

13. Have clinically relevant abnormal laboratory results, specifically including
hypokalemia.

14. Have a specific medical condition where LDX use is contraindicated, such as narrow
angle glaucoma or Tourette's syndrome.

15. Subjects requiring treatment with any drug which might interact adversely with or
obscure the action of the study medication. This includes warfarin, anticonvulsants,
clonidine, theophylline, and pseudoephedrine.

16. Subjects who have received any psychotropic medications (other than hypnotics) within
two weeks prior to LDX initiation, including monoamine oxidase inhibitors,
tricyclics, selective serotonin reuptake inhibitors, antipsychotics, mood
stabilizers, or psychostimulants.

17. Subjects who have received investigational medications or depot neuroleptics within
three months prior to LDX initiation.

18. Subjects who have a known allergy to LDX or its constituents

19. An MRI scan is contraindicated in the subject for safety reasons, claustrophobia, or
if the patient exceeds the weight limit of MRI scanner, ~350 pounds.