Pharmacokinetic Study for IV Allopregnanolone

Purpose

About 6.4% of the U.S. population suffers from posttraumatic stress disorder (PTSD). Trauma-focused psychotherapies are generally effective in PTSD, but responses vary greatly across individuals and PTSD subpopulations. Neurobiological factors impacted by life experiences, stress, and genetics can affect treatment responses. These factors can alter brain capacities needed to reprocess traumatic memories to prevent them from triggering intense, distressing, disruptive, out-of-place responses. Before starting the interventional study (described in detail in NCT07079761), the investigators will conduct two pharmacokinetic (PK) studies (PK-1 and PK-2) in a small group of individuals with PTSD to test dosing and safety at Boston Medical Center.

Conditions

  • Pharmacokinetic Study
  • Post Traumatic Stress Disorder

Eligibility

Eligible Ages
Between 18 Years and 55 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Chronic Posttraumatic Stress Disorder - Generally healthy and not on any prohibited medications (that could affect study outcomes) - Willing to abstain from alcohol for 2 weeks and from nicotine, marijuana or illicit drugs for 4 weeks before experimental procedures and throughout the study - Females: must have a menstrual cycle and not be on hormonal birth control (with a few exceptions; see below) - If gender non-conforming: must not be on hormone therapy

Exclusion Criteria

  • Bipolar I disorder, schizophreniform disorder, or clinically significant psychotic symptoms apart from the presence of trauma-related sensory hallucinations or negative beliefs - Moderate or severe substance use disorder within three months of screening - Sleep Apnea - History of a suicide attempt within 1 year of enrolling - Imminent risk to self or others or requiring clinical intervention to maintain safety - Unstable medical condition or condition that may affect outcomes - Moderate or severe traumatic brain injury (TBI) (mild TBI acceptable; moderate TBI allowed for PK study) - Using any medications or substances (per self-report or toxicology testing) that may increase the risk for IV Allo side effects or affect the experimental results. - Unable to tolerate IV placement or blood drawing by needle stick - Wear hearing aids or fail hearing test (not applicable to PK study) - Females: pregnant, breastfeeding, or if of childbearing potential, unwilling to use two forms of effective birth control [except for hormonal contraceptives, unless intrauterine device (IUD) or a device like NuvaRing] for one week before and one month after study drug administration

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Other
Masking
None (Open Label)
Masking Description
These pharmacokinetic (PK) studies are open-label studies confirming the dosing and safety of dosing for the main studies in NCT07079761.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
PK-1 Group 		Participants assigned to this group received IV allopregnanolone as a 5-minute loading dose at 1.7 mcg/kg followed by a maintenance infusion at 2.6 mcg/kg/hr over the next 4-5 hours intended to optimize resting plasma allopregnanolone + pregnanolone levels while outcomes were measured.
  • Drug: PK-1 Good Manufacturing Practices (GMP) allopregnanolone (Allo) with Dexolve in 0.9% saline for infusion manufactured by the University of California, Davis
    For the PK-1 group, after the 5-minute loading dose of IV allopregnanolone, the dose was changed as prescribed to optimize the subject's target plasma allopregnanolone + pregnanolone level for the next 4-5 hours.
    Other names:
    • U.S.P. equivalent: brexanolone (IV Allopregnanolone with Captisol) (SAGE Therapeutics)
Experimental
PK-2 Group 		Participants assigned to this group received a 30-minute drug infusion of IV allopregnanolone of 28 mcg/kg, The IV allopregnanolone then was discontinued and only normal saline was continued for the next 4-5 hours while outcomes were measured.
  • Drug: PK-2 GMP allopregnanolone (Allo) with Dexolve in 0.9% saline for infusion manufactured by the University of California, Davis.
    For the PK-2 group, after the 30-minute drug infusion of IV allopregnanolone, the IV allopregnanolone was discontinued and only normal saline was continued for the next 4-5 hours.
    Other names:
    • U.S.P. equivalent: brexanolone (IV allopregnanolone with Captisol) (SAGE Therapeutics)

More Details

Status
Terminated
Sponsor
Boston University

Study Contact