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

NCT05254405 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: Brex PTSD
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Post-Traumatic Stress Disorder

Keywords

PTSD; Women; Trauma

Outcome Measures

Primary Outcomes (1)

• Change in PTSD Symptom Severity: PTSD Checklist for DSM-5 (PCL-5)

  The primary efficacy outcome measure is change in PTSD Checklist for DSM-5 (PCL-5) total score from baseline at study endpoint (i.e., Week 12/Day 90). The PCL-5 is a 20-item self-report measure that assesses the presence and severity of PTSD symptoms. Items on the PCL-5 correspond with DSM-5 criteria for PTSD.

  Through study endpoint (Week 12 / Day 90)

Secondary Outcomes (3)

• Change in PTSD Subscale Symptoms: PTSD Checklist for DSM-5 (PCL-5)

  Through study endpoint (Week 12 / Day 90)

• Change in Depressive Symptoms: Montgomery-Asberg Depression Rating Scale (MADRS)

  Through study endpoint (Week 12 / Day 90)

• Change in Functional Capacity: Sheehan Disability Scale (SDS)

  Through study endpoint (Week 12 / Day 90)

Other Outcomes (3)

• Sedation: Stanford Sleepiness Scale (SSS)

  Up to 6 hours following completion of brexanolone infusion on Day 3.

• Suicidal Ideation: Columbia Suicide Severity Rating Scale (C-SSRS)

  Through study endpoint (Week 12 / Day 90)

• Pulse Oximetry

  Up to 6 hours following completion of brexanolone infusion on Day 3.

Study Arms (1)

Open-Label Infusion of Brexanolone

EXPERIMENTAL

This is a single arm pilot study of open label brexanolone delivered intravenously over a continuous 60-hour period. Infusions will be administered in a certified healthcare setting in accordance with the Zulresso™ dosing, administration and safety guidelines.

Drug: Brexanolone Injection [Zulresso]

Interventions

Brexanolone Injection [Zulresso] DRUG

Continuous infusion of brexanolone over 60 hours titrated to a maximal dose of 90 mcg/kg/hr.

Also known as: Zulresso

Open-Label Infusion of Brexanolone

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has signed an ICF prior to any study-specific procedures being performed
• Subject is a premenopausal female between 18 and 50 years of age, inclusive
• 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.
• PCL-5 total score ≥ 33 at screening and baseline (Day 0)
• 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
• Subject agrees to adhere to the study requirements
• Subject must have a negative pregnancy test at screening and Day 1 prior to the start of study drug infusion
• 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.
• Fluency (oral and written) in the language in which standardized tests will be administered.
• 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

You may not qualify if:

• Subject is currently pregnant, breastfeeding, or postpartum less than 6 months since end of pregnancy
• Subject has renal failure requiring dialysis or fulminant hepatic failure or is anemic (hemoglobin ≤10 g/dL)
• Known allergy to progesterone or allopregnanolone or any other neuroactive steroid GABAA receptor modulator.
• Active psychosis per Investigator assessment
• 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
• Medical history of bipolar disorder, schizophrenia, and/or schizoaffective disorder.
• History of seizure disorder.
• Subject has previously been treated with brexanolone or participated in any study employing SAGE-547, SAGE-217, SAGE-324, or SAGE-718.
• Concomitant treatment with benzodiazepines or other CNS depressants; initiation of any psychotropic agents within 14 days of screening.
• 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

Sponsors & Collaborators

• Donald Jeffrey Newport: lead
• Sage Therapeutics: collaborator

Study Sites (1)

University of Texas at Austin Dell Medical School

Austin, Texas, 78712, United States

RECRUITING

Related Publications (6)

• Dunlop BW, Kaye JL, Youngner C, Rothbaum B. Assessing Treatment-Resistant Posttraumatic Stress Disorder: The Emory Treatment Resistance Interview for PTSD (E-TRIP). Behav Sci (Basel). 2014 Dec 8;4(4):511-527. doi: 10.3390/bs4040511.

  PMID: 25494488 BACKGROUND

• MacLean AW, Fekken GC, Saskin P, Knowles JB. Psychometric evaluation of the Stanford Sleepiness Scale. J Sleep Res. 1992 Mar;1(1):35-39. doi: 10.1111/j.1365-2869.1992.tb00006.x.

  PMID: 10607023 BACKGROUND

• Nitzan M, Romem A, Koppel R. Pulse oximetry: fundamentals and technology update. Med Devices (Auckl). 2014 Jul 8;7:231-9. doi: 10.2147/MDER.S47319. eCollection 2014.

  PMID: 25031547 BACKGROUND

• Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011 Dec;168(12):1266-77. doi: 10.1176/appi.ajp.2011.10111704.

  PMID: 22193671 BACKGROUND

• Sarason IG, Johnson JH, Siegel JM. Assessing the impact of life changes: development of the Life Experiences Survey. J Consult Clin Psychol. 1978 Oct;46(5):932-46. doi: 10.1037//0022-006x.46.5.932. No abstract available.

  PMID: 701572 BACKGROUND

• Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.

  PMID: 9881538 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Wounds and Injuries

Interventions

brexanolone

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Donald J Newport, MD

  University of Texas at Austin/ Dell Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fouzia Sheikh

CONTACT

512-495-5566; psychclinicaltrials@austin.utexas.edu

Madeline Sheehan

CONTACT

512-495-5566; psychclinicaltrials@austin.utexas.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single-arm open-label study of brexanolone infusion for the treatment of posttraumatic stress disorder (PTSD) in adult women.

Study Record Dates

• First Submitted: January 26, 2022
• First Posted: February 24, 2022
• Study Start: June 1, 2023
• Primary Completion: December 1, 2025
• Study Completion: March 1, 2026
• Last Updated: May 22, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be made available after completion of study activities including publication of primary study results.

Locations

US (1)