Study Design and Methodology:~Open label study enrolling 20 subjects in which diagnosis of PTSD will be established, PTSD and depressive symptom severity will be assessed with validated psychometric instruments. Patient will be treated with continuous IV infusions of brexanolone at our affiliate hospital, Ascension Seton Medical Center, using the intravenous dose regimen previously approved by the FDA for postpartum depression. Following infusion, biweekly follow-up visits will be conducted for 12 weeks after the infusion. Subjects must remain as inpatients during the study Treatment Period, which is approximately 72 hours/3 days in duration (60 hours of treatment and an additional 12 hours for completion of 72-hour assessments). The Screening Period assessments may be conducted on an inpatient or an outpatient basis. The Follow-up Period assessments are conducted on an outpatient basis.~Screening Period: The Screening Period begins with the signature of the informed consent form (ICF). Eligibility is determined by applying the inclusion/exclusion criteria. The diagnosis of PTSD (associated with non-military trauma) must be established by the Mini International Neuropsychiatric Interview (MINI). A full medical examination, including laboratory tests and family history, will be taken from the subject.~Treatment Period: Once subjects are confirmed as eligible for the study, they will be scheduled for inpatient hospital admission where the continuous IV infusion of brexanolone will be administered over a 60-hour period. The infusion will be administered in accordance with the safe-use conditions, protocols and prescribing requirements of the FDA approved Zulresso (brexanolone) Risk Evaluation and Mitigation Strategies (REMS) NDA #211371. Throughout the infusion, all subjects will be continuously monitored for hypoxia using a pulse oximeter equipped with an alarm. Subjects will be assessed for excessive sedation every two hours during non-sleep periods. The infusion will be paused and/or discontinued if excessive sedation or hypoxia occur. Infusion rates will be programmed to increase and then taper with all subjects receiving 30 µg/kg/hour (0-4 hours), then 60 µg/kg/hour (4-24 hours), then 90 µg/kg/hour (24-52 hours), followed by 60 µg/kg/hour (52-56 hours), and 30 µg/kg/hour (56- 60 hours). Subjects may be discharged after the 72-hour assessments have been completed (12 hours after completion of the study drug infusion). If their clinical condition does not allow discharge, normal standard of care will be employed in their ongoing management. All subjects will be cautioned against engaging in potentially hazardous activities requiring mental alertness following the infusion.~Initiation of benzodiazepines, narcotics, antibiotics, neuroleptics, and other anti-anxiety medications will not be allowed between screening and completion of the 72-hour assessments. Doses of psychotropics, which must have been initiated at least 14 days prior to screening, must remain at a stable dose until completion of the 72-hour assessments.~Efficacy and safety assessments will be performed periodically during the study as outlined in the Schedule of Events (Table 1). Blood samples will be collected prior to the infusion, and outcome measures will be obtained at pre-specified times over 72 hours during the Treatment Period.~Follow-up Period: Follow-up Visits will be conducted one week (7±1 day), two weeks (14±2 days), one month (30±3 days), two months (60±3 days), and three months (90±3 days) after the initiation of the brexanolone infusion. After completion of their three month follow-up visit all subjects will be exited from the study.~Potential clinical benefit (efficacy) will be ascertained by estimating the treatment effect of brexanolone infusion through 3 months on measures of PTSD and depression symptom severity commonly used in clinical trials. Safety and tolerability will be assessed throughout the study by ascertainment of adverse events (AEs) including serious AEs throughout the study.
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