Safety, Tolerability and Activity of SRX246 in Adults With Intermittent Explosive Disorder

This exploratory Phase II study has been designed to examine the safety and tolerability
profile, and to compare the activity of the novel V1a vasopressin antagonist (SRX246)
against placebo, in adults with DSM-5 Intermittent Explosive Disorder (IED).

Adult Male and Female subjects with a current DSM-5 diagnosis of IED will be enrolled. All
subjects will undergo systematic diagnostic assessment for DSM-5 Axis I and II disorders.
Subjects with DSM-5 IED (without current, co-morbid, DSM-5 Major Depression) whose: (a) Life
History of Aggression (LHA) score is > 12, (b) Overt Aggression Scale Modified (OAS-M)
"Irritability" score is > 6 and, (c) screening OAS-M "Aggression" score is > 15, will be
entered into a two-week baseline lead-in phase.

After the lead-in phase, study subjects who continue to meet OAS-M criteria will be
randomized to one of the two (2) treatment conditions and stratified by gender so that equal
numbers of males and females are assigned to SRX246 and Placebo Groups. Those who do not
meet the criteria will exit the protocol at that time. Treatment Conditions: (a) 8-week
course of SRX246 (4 weeks at 120 mg bid, and 4 weeks at 160 mg bid) or (b) 8-week course of
Placebo, followed by a one-week "taper" to withdraw subjects from study medication.

IED subjects in all conditions will have structured diagnostic interview sessions and
questionnaires administered throughout the trial. Blinding to treatment condition will be
maintained by using different personnel for these activities. Analysis of a change from
baseline in the diagnostic measures will be performed.

Inclusion Criteria:

- Male or Female (Women of child bearing potential must be non-pregnant, non-lactating
and agree to be on an acceptable method of contraception.)

- Age 21 to 55 years, inclusive.

- In good general physical health as determined by medical history, a baseline physical
examination, vital signs, clinical laboratory tests and electrocardiogram (EKG)
measurement.

- Current IED by DSM-5

- LHA-Aggression ≥ 12.

- OAS-M Irritability score ≥ 6, and OAS-M Total Aggression score ≥ 15, respectively at
Visit 1

- Mean Irritability and Total Aggression scores for Visit 2 and Visit 3, ≥ 6 and ≥ 15,
respectively.

- Subject is willing and able to sign written informed consent prior to receipt of any
study medication or beginning study procedures.

- Subject is willing and able to follow instructions, comply with the protocol
requirements and make all required study visits.

Exclusion Criteria:

- Subject with a positive test for alcohol and/or drugs of abuse at screening or at any
time during the study.

- Presence of any of the following serious and active medical conditions: Seizure
Disorder (n.b.: history of < 2 febrile seizures prior to one year of age is
acceptable); Demyelinating or Progressive Degenerative Disorders; central nervous
system (CNS) Infection; Progressive Degenerative Neurological Disorder; Ischemic
Heart Disease, Respiratory Disease, Renal Disease; Liver Disease; Type I Diabetes;
Malignant Neoplasm; Hyper- or Hypo-Coagulopathy; Acquired Immuno-Deficiency Syndrome
(AIDS).

- Routine or as needed consumption of medications or herbal supplements that the
subject is unable or unwilling to discontinue during the study.

- Other ongoing psychotherapeutic treatment for the treatment of IED or anger begun
less than three months before entry into this study.

- Not Current DSM-5 IED.

- LHA score < 12 at Visit 1 (screen).

- OAS-M Irritability score < 6 or OAS-M Total Aggression score < 15 at Visit 1
(screen).

- Current major depressive episode or life history of bipolar disorder, schizophrenia,
organic mental syndrome, or mental retardation.

- Current DSM-5 Substance Use Disorder of moderate or greater severity (i.e., ≥ 4 SUD
symptoms).

- Active suicidal ideation as determined by clinical assessment and Columbia-Suicide
Severity Rating Scale (C-SSRS).

- Evidence of any out-of range laboratory value at screening that has not been
reviewed, approved and documented as not clinically significant by the Study
Investigator.

- A history of significant drug allergy or systemic allergic disease (e.g., urticaria,
atopic dermatitis), or any known/suspected hypersensitivity to SRX246.

- A general medical or psychological condition or behavior, including current substance
dependence or abuse that, in the opinion of the investigator, might not permit the
subject to complete the study or sign the informed consent.

- Unwilling/unable to sign informed consent document.

- Any clinically significant abnormality on screening resting 12-lead EKG (e.g., heart
block, conduction disorders, ventricular and/or atrial arrhythmias).

- Any other condition or clinically significant abnormal findings on the physical
examination, medical history, or clinical laboratory results during screening that,
in the opinion of the Study Investigator, would make the subject unsuitable for the
study or put them at additional risk.

- Inability to understand or follow study instructions.

- Treatment with an investigational drug within 30 days preceding the first dose of
study medication.

- Women who are currently breastfeeding and/or lactating.