Safety, Tolerability and Activity of SRX246 in Adults With Intermittent Explosive Disorder (AVN009)

• ClinicalTrials.gov Identifier: NCT02055638
• Recruitment Status: Completed
• First Posted: February 5, 2014
• Results First Posted: October 29, 2019
• Last Update Posted: October 29, 2019
• Sponsor: Azevan Pharmaceuticals
• Information provided by (Responsible Party): Azevan Pharmaceuticals

Tracking Information

• First Submitted Date: February 3, 2014
• First Posted Date: February 5, 2014
• Results First Submitted Date: January 17, 2018
• Results First Posted Date: October 29, 2019
• Last Update Posted Date: October 29, 2019
• Study Start Date: May 2014
• Actual Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 8, 2019)

Safety and Tolerability, Measured as the Number of Participants With Adverse Events [ Time Frame: up to 8 weeks ]

Number of participants with adverse events

Original Primary Outcome Measures (submitted: February 4, 2014)

safety and tolerability [ Time Frame: weekly up to 8 weeks ]

physical exam, vital signs, electrocardiogram, hematology, serum chemistry, urinalysis, adverse event (AE)/serious adverse event (SAE) reports

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: February 4, 2014)

Reduction in Total Aggression Score [ Time Frame: weekly up to 8 weeks ]

Determine the activity of SRX246 in reducing aggression in IED patients using diagnostic questionnaires and interview sessions

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability and Activity of SRX246 in Adults With Intermittent Explosive Disorder
• Official Title: An Exploratory Phase II Study to Determine the Safety, Tolerability and Activity of a Novel Vasopressin 1a Receptor Antagonist (SRX246) in Adults With Diagnostic and Statistical Manual Version 5 (DSM-5) Intermittent Explosive Disorder (IED)

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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Intermittent Explosive Disorder

Intervention

• Drug: SRX246
  capsules
• Drug: Placebo

Study Arms

• Experimental: SRX246
  SRX246 capsules, 120mg bid for 4 weeks followed by 160mg bid for 4 weeks
  Intervention: Drug: SRX246
• Placebo Comparator: Placebo
  Placebo capsules to match the amount of SRX246 capsules for 8 weeks
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 8, 2019): 97
• Original Estimated Enrollment (submitted: February 4, 2014): 96
• Actual Study Completion Date: May 2016
• Actual Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02055638
• Other Study ID Numbers: AVN009
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Azevan Pharmaceuticals
• Study Sponsor: Azevan Pharmaceuticals
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Azevan Pharmaceuticals
• Verification Date: October 2019