An Open Label Pilot Study of IV Brexanolone for the Treatment of Post-Traumatic Stress Disorder

• Status: Not yet recruiting
• Trial end date: 2025-03-01
• Target enrollment: 0
• Participant gender: Female

Summary

Open-label study of brexanolone infusion for the treatment of posttraumatic stress disorder in 20 adult women with PTSD.

Primary Objective:

To determine if brexanolone injection infused intravenously for 60 hours at up to 90 μg/kg/h reduces PTSD symptom severity in a group of non-veteran adult female subjects diagnosed with PTSD as assessed by the change from baseline in the PTSD Checklist for DSM-5 (PCL-5) total score and rate of remission at 12-weeks post infusion.

Secondary Objectives

• To evaluate the safety and tolerability profiles of brexanolone in this PTSD patient population as assessed by the incidence of adverse events (AEs), vital sign measurement, the Stanford Sleepiness Scale (SSS) and the Columbia Suicide Severity Rating Scale (C-SSRS).

• To determine the effects of brexanolone in reducing depressive symptoms and improving functional capacity in PTSD patients as assessed by change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score and Sheehan Disability Scale scores

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Donald Jeffrey Newport
• Collaborator: Sage Therapeutics
• Treatments: Brexanolone

Criteria

Inclusion Criteria:

1. Subject has signed an ICF prior to any study-specific procedures being performed

2. Subject is a premenopausal female between 18 and 50 years of age, inclusive

3. Subject has a current diagnosis of PTSD associated with civilian (i.e., non-military) trauma according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and confirmed by the Mini International Neuropsychiatric Interview (MINI) at the screening visit.

4. PCL-5 total score ≥ 33 at screening and baseline (Day 0)

5. Subject is in good physical health and has no clinically significant findings, as determined by the Investigator, on physical examination, 12-lead ECG, or clinical laboratory tests

6. Subject agrees to adhere to the study requirements

7. Subject must have a negative pregnancy test at screening and Day 1 prior to the start of study drug infusion

8. Subject is willing at screening to delay the start of any new pharmacotherapy regimens, including antidepressant or anti-anxiety medication, until the study drug infusion and 72-hour assessments have been completed; if the subject is taking psychotropic medications, these must be at a stable dose from 14 days prior to screening until the 72-hour assessments have been completed.

9. Fluency (oral and written) in the language in which standardized tests will be administered.

10. Subject must use one of the following methods of birth control during participation in the study and for 30 days following the end of the study drug infusion:

• Total abstinence (no sexual intercourse)

• Hormonal contraceptives (birth control) including birth control pills, implantable or injectable contraceptives (Norplant® or DepoProvera®)

• A barrier form of contraception such as a condom or occlusive cap with a spermicide

• An intrauterine device

Exclusion Criteria:

1. Subject is currently pregnant, breastfeeding, or postpartum less than 6 months since end of pregnancy

2. Subject has renal failure requiring dialysis or fulminant hepatic failure or is anemic (hemoglobin ≤10 g/dL)

3. Known allergy to progesterone or allopregnanolone or any other neuroactive steroid GABAA receptor modulator.

4. Active psychosis per Investigator assessment

5. At risk for suicide in the opinion of the investigator or answers "yes" to "Suicidal Ideation" Item 4 or 5 on the CSSRS (at the time of evaluation) at the screening visit

6. Medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder.

7. History of an active substance use disorder in the 6 months prior to screening. A positive urine drug screen (except benzodiazepines under certain circumstances is exclusionary.

8. History of seizure disorder.

9. Subject has previously been treated with brexanolone or participated in any study employing SAGE-547, SAGE-217, SAGE-324, or SAGE-718.

10. Concomitant treatment with benzodiazepines or other CNS depressants; initiation of any psychotropic agents within 14 days of screening.

11. Any current or recent medical, psychiatric or social condition which in the investigator's opinion is likely to interfere with the conduct of the study, confound the interpretation of study results, or endanger the subject's well-being. This includes (but is not limited to) any clinically significant oncologic, hematologic, endocrine/metabolic, cardiovascular, respiratory, renal, hepatic, gastrointestinal, infectious or