An Exploratory, Single-Blind Pilot Study Of Flexible Doses of the Triple Reuptake Inhibitor EB-1020 SR in the Treatment of Adult Males With Attention-Deficit Hyperactivity Disorder

This Phase 2, flexible-dosage, single-blind study consists of a Screening Phase (up to 28
days [Visit 1]), a 5-week Treatment Phase (1 week of treatment with placebo
[Baseline-1/Visit 2 to Baseline-2/Visit 3] followed by 4 weeks of treatment with EB-1020 SR
[Weeks 1 through 4/Visits 4 through 7]), and a 2-week Discontinuation Phase, which starts at
the time of Week 4/Visit 7 and includes a Follow-up Visit (Week 6/Visit 7). Approximately 40
patients are planned to enter the treatment period. At Baseline-1, patients must have a
score of greater than or equal to 28 on the ADHD-RS-IV to be eligible to continue
participation in the study. At the end of single-blind placebo treatment (i.e., Baseline-2),
the ADHD-RS-IV with adult prompts is re-administered. Patients who show an improvement
greater than or equal to 30% over baseline values or who have a score of less than 28 on the
ADHD-RS-IV are withdrawn from the study prior to receiving any active drug. Those who show
less than 30% improvement from Baseline-1 to Baseline-2 scores will continue in the study.
The consent form will be phrased such that patients are not informed of the exact timing of
EB-1020 SR vs. placebo treatment in order to maintain the blinded nature of the placebo
treatment and reduce potential placebo effects. Dosing will be flexible, with a target
maximum dosage of 500 mg daily in divided doses (morning and afternoon, approximately 5
hours later) to be achieved if possible during Week 2 of EB-1020 SR treatment. The patient
will take a starting dose of 100 mg of EB-1020 SR daily; the dose will be titrated in 100 mg
increments up to the maximum dosage of 500 mg daily. The treating physician will escalate
the dose to the maximum dose if patients have not achieved remission of ADHD in his/her
judgment, and EB-1020 SR is still well tolerated. If in the physician's judgment the patient
could not tolerate further dose escalation, or is not tolerating the current dose well, the
dose may be maintained or reduced, with the goal of re-assessing dose and response at the
subsequent visit for a possible increase in dose, until study completion.

Inclusion Criteria:

Signed Written Informed Consent

1. Patients must be able to give informed consent, as required by the Institutional Review
Board (IRB), prior to the initiation of any procedures required per protocol.

Target Population

1. Patients must be able to understand the nature of the study, agree to comply with the
prescribed dosage regimens, report for regularly scheduled office visits, and
communicate to study personnel about adverse events and concomitant medication use.

2. Patients must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision (DSM-IV-TR) diagnostic criteria for ADHD (Combined,
Predominantly Inattentive or Predominantly Hyperactive-Impulsive Types) on the Mini
International Neuropsychiatric Interview Plus, Version 6.0 (M.I.N.I.-Plus)

3. Patients must have an ADHD-RS-IV score of greater than or equal to 28 at Baseline-1
and Baseline-2.

4. Patients must have a CGI-S (ADHD version) score of greater than or equal to 4.

5. Patients must be male.

6. Patients must be 18 to 55 years old, inclusive.

7. Patients must be able to read well enough to understand the informed consent form and
other patient materials.

8. Patients must be able to be reliably rated on the psychiatric scales required by the
protocol based on investigator's judgment.

9. Patients must be able to read and understand English.

10. Patients must have a body mass index (BMI) of approximately 18 to 35 kg/m2. The BMI
is to be calculated using the following formula: mass (lb) x 703/(height (in))2.
Guidelines for this calculation will be provided to the investigational centers.

Sex and Contraceptive Criteria

1. Sexually active, fertile males must use effective birth control if their partners are
women of childbearing potential. Adequate birth control methods for both males and
females (as appropriate) are defined as those which result in a low failure rate
(i.e., less than 1% per year) when used consistently and correctly such as implants,
injectable or patch hormonal contraception, oral contraceptives, an IUD,
double-barrier contraception, or true sexual abstinence. The form of birth control
for the male and/or partner, where relevant, must be documented at screening and
baseline.

2. Women of childbearing potential (if a partner of a male participant) include any
female who has experienced menarche and who has not undergone successful surgical
sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or
is not postmenopausal (defined as amenorrhea greater than or equal to 12 consecutive
months); or women on hormone replacement therapy [HRT] with documented serum follicle
stimulating hormone [FSH] level greater than 35 mIU/mL. Even women who are using oral
contraceptives, other hormonal contraceptives (vaginal products, skin patches, or
implanted or injectable products), or mechanical products such as an intrauterine
device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or
are practicing abstinence or where the partner is sterile (e.g., vasectomy), should
be considered to be of childbearing potential.

Exclusion Criteria:

1. Patient has a DSM-IV-TR diagnosis of ADHD not otherwise specified (NOS).

2. Patients rated as having a greater than or equal to 30% improvement in ADHD symptoms
or a score of less than 28 on the ADHD-RS-IV after Week 1 (placebo lead-in). Such
patients will be withdrawn from the study prior to receiving any active drug.

3. Patient has a current or lifetime history of bipolar disorder or any psychotic
disorder as established by M.I.N.I.-Plus.

4. Patient has a current history (past 90 days) of major depression, generalized anxiety
disorder, obsessive-compulsive disorder, panic disorder or post-traumatic stress
disorder as established by the M.I.N.I.-Plus.

5. History in the past 20 years of electroconvulsive therapy (ECT) or lifetime history
of vagal nerve stimulation or deep brain stimulation for the treatment of depression.

6. Patients with a history of drug or alcohol use disorders (abuse or dependence) must
have been free of the diagnosis and of substance use for at least 6 months prior to
the Screening visit.

7. Patient has a history of epilepsy, seizures, syncope, unexplained blackout spell(s),
head trauma with clinically significant loss of consciousness or noninfantile febrile
seizures.

8. Patient has a currently active medical condition (other than ADHD) that, in the
opinion of the investigator, could interfere with the ability of the patient to
participate in the study safely.

9. Patient has a history of clinically significant, diagnosed cardiovascular disease of
any kind, including uncontrolled hypertension. Patient has newly diagnosed
cardiovascular disease of any kind in the investigator's judgment.

10. The patient has an IQ less than 80.

11. In the opinion of the investigator, the patient has not derived significant
therapeutic benefit from 2 or more ADHD therapies given with an adequate dose and
duration in adulthood (age 18 or older); i.e., 1 failed course of treatment is
acceptable, but 2 failed courses of treatment are not acceptable.

12. Patient taking medication specifically for treatment of ADHD symptoms (e.g.,
stimulants, atomoxetine, tricyclic antidepressants, bupropion, modafinil, etc) must
be off stimulants for 2 weeks and off nonstimulant ADHD therapies for 3 weeks prior
to the Baseline-1 Visit and must have returned to the baseline level of ADHD symptoms
in the opinion of the investigator. Patients must not have evidence of a
discontinuation or withdrawal reaction.

13. Patient is currently taking any antidepressant medication for any condition.

14. Patient is currently taking antipsychotic medication, or an anticonvulsant medication
(e.g., phenytoin, carbamazepine, lamotrigine, or valproic acid) at anticonvulsant
doses.

15. Patient has a known history of allergy to EB-1020.

16. Patient is unwilling to refrain from taking medications that may interfere with the
assessment of cognitive function and the assessment of sleep. Examples include
benzodiazepines, sedating antihistamines, zolpidem, eszopiclone, and zaleplon. Herbal
preparations with effects on the central nervous system also are prohibited
throughout the study, (e.g., St. John's Wort or melatonin).

17. Patient has a history of sleep problems in the last 3 months.

18. Patient is unwilling to refrain from taking more than one unit of alcohol within 24
hours of the investigational center visits.

19. Patient is unwilling to restrict caffeine to no more than 500 mg/day (5 cups of
coffee).

20. Patient is actively using any drugs with potential for abuse (e.g., marijuana,
cocaine, amphetamines)

21. Patient reports passive or active suicidal ideation or intent.

22. Patient is concurrently participating in another clinical research study or
investigational drug study or has participated in such a study within the past 1
month.

23. Patient is at high risk of nonadherence to investigational product and the protocol
regimen in the investigator's opinion.

24. Patient may not begin psychotherapy during the study, but may continue therapy at the
same intensity and frequency, if begun at least 3 months prior to Baseline-1 Visit.
2.

Exclusion Criteria, Physical and Laboratory Test Findings

1. Patients who have a positive urine drug screen, which cannot be explained by
prescribed medications. The urine drug screen may be repeated based on investigator
judgment.

2. Patients with clinically significantly abnormal thyroid-stimulating hormone (TSH) or
a positive result on a standard hepatitis screening panel or human immunodeficiency
virus (HIV) screen. NOTE: Adequate thyroid replacement for a previously diagnosed
thyroid deficiency, which has been stable for 3 months or more, is acceptable.

3. Patients with clinically significant laboratory abnormalities or with clinical
laboratory values of potential clinical concern.

4. Diastolic blood pressure greater than 85 mm Hg at Baseline-1.

5. Systolic blood pressure greater than 135 mg Hg at Baseline-1.

6. Patient has a QT interval of greater than 450 ms on 2 or more ECG tracings taken
within 15 minutes, assessed with the patient in a supine position for 3 minutes.

Other Exclusion Criteria

1. Prisoners or patients who are involuntarily incarcerated.

2. Patients who have a compulsory detainment for treatment of either a psychiatric or
physical illness.

3. Patients who plan to have elective surgeries during the course of the study.

4. Patients with a history of antidepressant-induced hypomania or dysphoria.