Pharmacokinetic Study for IV Allopregnanolone

NCT04468360 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: H-40643R01MH122867
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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

Post Traumatic Stress Disorder; Pharmacokinetic Study

Keywords

Pharmacokinetic study; Allopregnanolone (Allo); Vital signs; Sedation ratings; Pulse oximeter data

Outcome Measures

Primary Outcomes (6)

• Clinician Assessed Sedation Levels for Each Participant

  Sedation levels will be assessed with the Qualitative Sedation Rating Scale. It has 5 categories: None- responds normally to verbal commands, cognitive \& coordination not impaired, ventilatory \& cardiovascular functions unaffected; Minimal- responds normally to verbal commands, unaffected ventilatory \& cardiovascular functions, mild feelings of intoxication, cognitive function \& coordination may be impaired; Moderate-responds purposefully to commands alone or with light touch, protective airway reflexes \& adequate ventilation maintained without intervention, cardiovascular function remains stable; Deep- cannot be easily aroused but responds purposefully to noxious stimulation, assistance may be needed to ensure the airway is protected \& adequate ventilation maintained, cardiovascular function is usually stable; Dissociative- trance-like cataleptic state with profound analgesia \& amnesia, airway protective reflexes, spontaneous respirations \& cardiopulmonary stability retained.

  resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes

• Blood Oxygen Saturation

  Average across participants of blood oxygen saturation levels obtained via pulse oximetry (ranging from 0% to 100%) for each time point indicated.

  resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes

• Respiratory Rate

  Average across participants of respiratory rate for each time point indicated.

  resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes

• Pulse Rate

  Average across participants of pulse rate for each time point indicated.

  resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes

• Diastolic Blood Pressure

  Average across participants of diastolic blood pressure for each time point indicated.

  resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes

• Systolic Blood Pressure

  Average across participants of systolic blood pressure for each time point indicated.

  resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes

Study Arms (2)

PK-1 Group

EXPERIMENTAL

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

PK-2 Group

EXPERIMENTAL

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.

Interventions

PK-1 Good Manufacturing Practices (GMP) allopregnanolone (Allo) with Dexolve in 0.9% saline for infusion manufactured by the University of California, Davis DRUG

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.

Also known as: U.S.P. equivalent: brexanolone (IV Allopregnanolone with Captisol) (SAGE Therapeutics)

PK-1 Group

PK-2 GMP allopregnanolone (Allo) with Dexolve in 0.9% saline for infusion manufactured by the University of California, Davis. DRUG

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.

Also known as: U.S.P. equivalent: brexanolone (IV allopregnanolone with Captisol) (SAGE Therapeutics)

PK-2 Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): collaborator
• Boston University: lead

Study Sites (1)

Boston University Chobanian & Avedisian School of Medicine

Boston, Massachusetts, 02118, United States

Location

Related Publications (23)

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• Milad MR, Zeidan MA, Contero A, Pitman RK, Klibanski A, Rauch SL, Goldstein JM. The influence of gonadal hormones on conditioned fear extinction in healthy humans. Neuroscience. 2010 Jul 14;168(3):652-8. doi: 10.1016/j.neuroscience.2010.04.030. Epub 2010 Apr 22.

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• Monfils MH, Cowansage KK, Klann E, LeDoux JE. Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Science. 2009 May 15;324(5929):951-5. doi: 10.1126/science.1167975. Epub 2009 Apr 2.

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• Norrholm SD, Anderson KM, Olin IW, Jovanovic T, Kwon C, Warren VT, McCarthy A, Bosshardt L, Sabree J, Duncan EJ, Rothbaum BO, Bradley B. Versatility of fear-potentiated startle paradigms for assessing human conditioned fear extinction and return of fear. Front Behav Neurosci. 2011 Nov 21;5:77. doi: 10.3389/fnbeh.2011.00077. eCollection 2011.

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• Norrholm SD, Jovanovic T, Olin IW, Sands LA, Karapanou I, Bradley B, Ressler KJ. Fear extinction in traumatized civilians with posttraumatic stress disorder: relation to symptom severity. Biol Psychiatry. 2011 Mar 15;69(6):556-63. doi: 10.1016/j.biopsych.2010.09.013. Epub 2010 Oct 29.

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• Oh MC, Derkach VA, Guire ES, Soderling TR. Extrasynaptic membrane trafficking regulated by GluR1 serine 845 phosphorylation primes AMPA receptors for long-term potentiation. J Biol Chem. 2006 Jan 13;281(2):752-8. doi: 10.1074/jbc.M509677200. Epub 2005 Nov 4.

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• Orr SP, Metzger LJ, Lasko NB, Macklin ML, Peri T, Pitman RK. De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. J Abnorm Psychol. 2000 May;109(2):290-8.

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• Orr SP, Milad MR, Metzger LJ, Lasko NB, Gilbertson MW, Pitman RK. Effects of beta blockade, PTSD diagnosis, and explicit threat on the extinction and retention of an aversively conditioned response. Biol Psychol. 2006 Oct;73(3):262-71. doi: 10.1016/j.biopsycho.2006.05.001. Epub 2006 Jul 7.

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• Pineles SL, Nillni YI, King MW, Patton SC, Bauer MR, Mostoufi SM, Gerber MR, Hauger R, Resick PA, Rasmusson AM, Orr SP. Extinction retention and the menstrual cycle: Different associations for women with posttraumatic stress disorder. J Abnorm Psychol. 2016 Apr;125(3):349-55. doi: 10.1037/abn0000138. Epub 2016 Feb 11.

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Related Links

• Parent study

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Pregnanolone; Sodium Chloride; SBE4-beta-cyclodextrin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Only preliminary data from pharmacokinetic studies were collected at Boston University School of Medicine/Boston Medical Center before the investigator moved to another institution where the actual research study is being conducted \[refer to NCT07079761\].

Results Point of Contact

• Title: Ann M. Rasmusson, MD
• Organization: Boston Medical Center/Boston University Chobanian and Avedisian School of Medicine

amrasmus@bu.edu

617-358-1871

Study Officials

• Ann M Rasmusson, MD

  Boston University Chobanian & Avedisian School of Medicine, Dept of Psychiatry

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: These pharmacokinetic (PK) studies are open-label studies confirming the dosing and safety of dosing for the main studies in NCT07079761.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: July 8, 2020
• First Posted: July 13, 2020
• Study Start: March 4, 2022
• Primary Completion: April 29, 2025
• Study Completion: April 29, 2025
• Last Updated: June 2, 2026
• Results First Posted: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)