An Open Label Pilot Study of IV Brexanolone for the Treatment of Post-Traumatic Stress Disorder
brief 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 24 hours at up to 60 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 self-assessment Montgomery-Asberg Depression Rating Scale (MADRS-S) total score and Sheehan Disability Scale scores
detailed description
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 an attenuated version of the intravenous dose regimen previously approved by the FDA for postpartum depression. Following infusion, 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 30 hours in duration (24 hours of treatment and an additional 6 hours for completion of assessments). The Screening Period and Follow Up Period assessments will be conducted on an outpatient basis. Follow Up visits can be conducted via telemedicine.
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 primary 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 24-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 at scheduled intervals during non-sleep periods. If a participant has a Stanford Sleepiness Scale (SSS) score of ≥5 for two or more consecutive assessments or an SSS score of ≥6 for a single occurrence during normal waking hours, the infusion rate for this subject will be decreased to the next lowest infusion dose level (or discontinued if this occurs at the 30 μg/kg/hour dose level). Infusion rates will be programmed for all subjects receiving 30 µg/kg/hour (Hours 0-2), and then 60 µg/kg/hour (Hours 2-24). Subjects may be discharged when the Hour 30 post-infusion assessments have been completed (6 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.