PT150 (formerly ORG 34517) as a Potential Treatment for Alcohol Dependence – Alcohol Interaction Study

Background:

Safe, effective treatments for post-traumatic stress disorder (PTSD) alone, alcohol use disorder (AUD) alone, and both illnesses occurring together are severely limited. There is a great need to develop effective treatments for PTSD, AUD, and co-occurring PTSD and AUD. An emerging awareness of the overlap in PTSD and AUD phenomenology, neural circuitry, and neurobiology provides a rationale to exploit these overlaps for pharmaceutical development for comorbid PTSD and AUD treatment [1, 2]. 

Objectives and Study Design:

The specific aim of this study is to evaluate the safety of study drug PT150 taken concurrently with alcohol consumption in 10 non-treatment seeking participants by evaluating pharmacodynamic and safety endpoints during alcohol challenge prior to, and after 5 days of PT150 treatment, when PT150 has reached steady state. The objectives of this aim is to compare pharmacodynamic and safety endpoints following an alcohol challenge prior to- and concurrent with PT150 treatment. 

Given available preclinical and clinical evidence for a salutatory effect of GR antagonists on alcohol withdrawal, the study team hypothesizes that PT150 will not significantly alter pharmacodynamic measures and be safe and well-tolerated under conditions of alcohol consumption [1, 2]. This human laboratory study is intended to provide human safety alcohol interaction data needed for the IND application for use of PT150 in Phase II and Phase III studies for treatment of AUD, PTSD and co- occurring AUD/PTSD.

This study can be classified as a Phase 1, single center, and drug study. This within-subjects experimental procedure will assess the effects of PT150 (900 mg qd) on the subjective effects of alcohol in non-treatment-seeking alcohol-experienced volunteers who are veterans. Participants will undergo two alcohol challenges on day 1 separated by 4 hours (one with alcohol, 0.8g/kg; 16% by volume, and one with  placebo beverage, 1% by volume, randomly ordered) and receive active study drug (PT150) from days 1-5 (after alcohol challenge for day 1). On day 5, the study drug dosing will be followed by two more alcohol challenges (alcohol and placebo beverage randomly ordered). Physiologic, subjective effects and BAL will be obtained after the alcohol challenges. Participants will be discharged on Day 6. 

Sources:

[1] Jacobsen, L. K., Southwick, S. M. & Kosten, T. R. Substance use disorders in patients with posttraumatic stress disorder: a review of the literature. Am J Psychiatry 158, 1184-1190 (2001). 

[2] Koob, G. F. The darkness within: individual differences in stress. Cerebrum 2015, 4 (2015).

 

At a Glance

Study type:

Phase I Clinical Trial

Objective:

To compare safety endpoints following an alcohol challenge prior to and concurrent with PT150 treatment

Population:

Adults of any race or ethnicity, males, and females who are post-menopausal, infertile and not hormone cycling, or using approved contraception. Potential enrollees will be drawn of those NOT seeking treatment or enrolled in Michael E. DeBakey Veterans Affairs Medical Center in Houston, TX

Number of participants:

10

Data collection:

TBD

Participating sites:

Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) in Houston, TX

Principal investigators:

Christopher Verrico, PhD, Baylor College of Medicine (BCM), Dewleen Baker, M.D., University of California, San Diego (UCSD), Thomas Newton, M.D., Baylor College of Medicine (BCM)

Duration:

4 months