Intermittent Explosive Disorder
Conditions
Keywords
Intermittent Explosive Disorder, IED, Aggression, SRX246, Vasopressin 1a Receptor Antagonist, V1a
Brief summary
This study is designed to explore the safety and tolerability, and to compare the activity of SRX246 against placebo, in adults with Intermittent Explosive Disorder (IED). Adult Male and Female subjects with a current diagnosis of IED will be enrolled. After a two-week baseline lead-in phase, study subjects who continue to meet enrollment criteria will be randomized to either SRX246 or Placebo treatment groups. Study subjects will be examined and asked to answer questionnaires at weekly scheduled visits throughout the trial. The study results will be determined based on any changes observed over the study period.
Detailed description
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.
Interventions
DRUGSRX246
capsules
DRUGPlacebo
Sponsors
Azevan Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
No
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 Substance Use Disorder (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | from initial dose of intervention until completion of the study up to 8 weeks | measured as the number of participants with adverse events |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overt Aggression Scale Modified (OAS-M) Total Aggression Score | Comparison of baseline score to score at end of treatment period of 8 weeks | Change from Baseline OAS-M Score. Higher values represent a worse outcome. The OAS-M contains 3 scales: Aggression (Questions \[Q\]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Aggression total score was calculated by summing the weighted scores in Q1 to 4. Scores for each question ranged from 0 (no events) to 5 (very severe events). Total scores ranged from 0 (no aggression) to any number with no upper limit depending on the frequency of aggressive behavior in a week. |
Countries
United States
Participant flow
Pre-assignment details
One additional subject was enrolled than planned, due to timing of screening and notification to sites of ceasing planned enrollment.
Participants by arm
| Arm | Count |
|---|---|
| SRX246 SRX246 capsules, 120mg bid for 4 weeks followed by 160mg bid for 4 weeks
SRX246: capsules | 49 |
| Placebo Placebo capsules to match the amount of SRX246 capsules for 8 weeks
Placebo | 48 |
| Total | 97 |
Baseline characteristics
| Characteristic | SRX246 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 48 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 43 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 31 Participants | 60 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 16 Participants | 12 Participants | 28 Participants |
| Region of Enrollment United States | 49 Participants | 48 Participants | 97 Participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Male | 29 Participants | 28 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 48 |
| other Total, other adverse events | 9 / 49 | 7 / 48 |
| serious Total, serious adverse events | 0 / 49 | 0 / 48 |
Outcome results
Primary
Safety and Tolerability
measured as the number of participants with adverse events
Time frame: from initial dose of intervention until completion of the study up to 8 weeks
Population: Intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SRX246 | Safety and Tolerability | adverse events (AE) | 28 participants |
| SRX246 | Safety and Tolerability | serious adverse events (SAE) | 0 participants |
| Placebo | Safety and Tolerability | adverse events (AE) | 21 participants |
| Placebo | Safety and Tolerability | serious adverse events (SAE) | 0 participants |
Other Pre-specified
Overt Aggression Scale Modified (OAS-M) Total Aggression Score
Change from Baseline OAS-M Score. Higher values represent a worse outcome. The OAS-M contains 3 scales: Aggression (Questions \[Q\]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Aggression total score was calculated by summing the weighted scores in Q1 to 4. Scores for each question ranged from 0 (no events) to 5 (very severe events). Total scores ranged from 0 (no aggression) to any number with no upper limit depending on the frequency of aggressive behavior in a week.
Time frame: Comparison of baseline score to score at end of treatment period of 8 weeks
Population: those that took study drug and had sufficient data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SRX246 | Overt Aggression Scale Modified (OAS-M) Total Aggression Score | -29.55 score on a scale | Standard Deviation 37.343 |
| Placebo | Overt Aggression Scale Modified (OAS-M) Total Aggression Score | -30.43 score on a scale | Standard Deviation 34.082 |