Initial Study Sesting Efficacy and Tolerability of PT150 for PTSD in Veterans

Phase 2a Trial: Efficacy and Safety of PT150 in the Treatment of US Veterans With Posttraumatic Stress Disorder (PTSD)

The purpose of this study is to test the drug PT150, which blocks glucocorticoid receptor (GR) signaling, for treatment of PTSD in Veterans, and establish a safety and efficacy profile that will inform the design of future studies.

This is a dual-site, proof-of-concept, parallel arm, double-blind placebo control study of a 14-day single daily dose of PT150/placebo in 100 Veterans with PTSD. Each site will enroll 60 Veterans with PTSD to ensure 100 study completers. Preclinical studies of PT150 and similar types of glucocorticoid antagonists have shown that they block stress responses in both acute and chronic models of stress response. PT150 has been tested previously in healthy control populations and in populations with depression, with it being found to be well tolerated and safe. Drug interaction results suggest it does not interact with alcohol or serotonin reuptake inhibitors, again supporting its safety and making it a candidate for further development. The goal of this Phase2a study is to tests its efficacy to reduce PTSD symptoms, as well as other biomarkers associated with PTSD. Participants first will undergo screening procedures, including a medical exam, clinical interview, self-report questionnaires, and blood draw. If eligible, they will be randomized to either PT150 or placebo. The PT150 dose will be titrated from 150-600mg over days 1-7, with the max dose of 900mg/day given the remaining 7 day timeframe. The same procedures will be repeated before, during and after taking the study drug or placebo for fourteen days. The key outcome measures will be obtained at baseline, day 28, and day 84.

Inclusion Criteria:

• Provide signed and dated informed consent form
• Be a military service member or Veteran
• Male or female, 18-65 years of age
• Meet DSM-5 criteria for PTSD ≥ 3 months duration as determined by CAPS-5
• Normal vitals and a baseline EKG with clinically normal sinus rhythm, clinically normal conduction, normal QTc, and no clinically significant arrhythmias
• Self-reported medical history and brief physical examination with no clinically significant contraindications for study participation
• Blood laboratory test results for routine hematology, chemistries, liver and kidney function tests within acceptable limits
• Willing to comply with all study procedures including taking oral medication, the study schedule and be available for the duration of the study Biological females, if able to conceive, must agree to use 2 forms of non-hormonal, medically acceptable contraception.

Exclusion Criteria:

• Severe alcohol or substance use disorders by DSM-5 criteria in past 3 months or positive urine test for substances other than cannabis
• History or diagnosis of neurodegenerative disorders, psychotic disorders or bipolar disorder. Current treatment with antipsychotic medication for mental health
• History of suicide attempts and/or current suicidal ideation with plan or intent
• Currently using psychotropic medication (except SSRI/SNRI) or other drugs or agents which might interact with study drug. Currently taking SSRI/SNRI antidepressants for less than 30 days. Benzodiazepines or sleep agents (e.g. eszopiclone; zolpidem) are excluded; exception: trazodone 25-50 mg qhs prn for sleep or prazosin for nightmares
• Be pregnant or nursing
• HRT dose not stable for a minimum of 3 months
• Evidence of a serious, chronic medical condition that would increase the risk of an adverse outcome or history of any serious metabolic or other disease known to affect the CNS
• Have evidence of untreated or unstable medical illness including cardiovascular, neuroendocrine, autoimmune, renal, hepatic, or active HIV+/AIDS infection
• Serious cognitive impairment likely to interfere with ability to meaningfully participate
• Past brain injury/head trauma with minor loss of consciousness and current symptoms or significant loss of consciousness
• Current signs of violence or aggression
• A history of adrenal insufficiency or a plasma cortisol level ≤ 5 mcg/dl at screening
• Receiving non-pharmacotherapy treatments or procedures for where precautions exist for taking with PT150 and/or those that might interfere with the study
• Contraindication(s) to take PT150 such as renal or hepatic impairment, congenital metabolic disorders, or hypersensitivity to study drug or similar compounds
• Participation in a pharmaceutical trial or use of investigational drugs within 1 month of screening
• Hearing loss that would interfere with the extinction recall measures
• Any other illness, condition, or use of medications which in the opinion of the PI and/or study investigator would preclude safe and/or successful completion of the study