Effects of Ethanol on the Pharmacokinetics of PT-150 (Formerly ORG34517) (PT150 PK Study)

This is an interventional treatment trial for Potential Treatment for Alcohol Dependence-Alcohol Interaction focused on measuring Alcohol, Alcoholic, Alcoholism, Alcohol abuse, Alcohol interaction, Alcohol Use Disorder, Alcohol use, Alcohol dependence, Alcohol dependent, Post Traumatic Stress Disorder, Substance use Disorder, Ethanol abuse, Ethanol use, Pharmacokinetics Read More

Inclusion Criteria:

1. Provide signed and dated informed consent form;
2. Male or female, aged 21-64;
3. Must score < 10 on the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar) assessed in the context of a BAL ≤ 0.00% to demonstrate that they do not need medical detoxification;
4. Must have blood lab test results within the acceptable limits noted in the protocol (Tests may be repeated if initial results are out of range);
5. Have normal vitals (heart rate 50-100 bpm, systolic blood pressure 90-140 mmHg and diastolic blood pressure 60-90 mmHg) and a baseline ECG that demonstrates clinically normal sinus rhythm, clinically normal conduction, normal QTc, and no clinically significant arrhythmias;
6. Have a self-reported medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician;
7. Must be willing to comply with all study procedures and be available for the duration of the study;
8. Women must either be unable to conceive (i.e., surgically sterilized, sterile, or post-menopausal) or using non-hormonal, medically acceptable contraception during the study and for at least 2 weeks after study completion, with or without additional hormonal contraception. Women can be receiving hormone replacement treatment (HRT) as long as the HRT dose has been stable for a period of at least 3 months;
9. Women must provide a negative urine pregnancy test within 30 days of alcohol administration on Day 1/baseline (i.e. during the screening period) and a negative serum pregnancy test on day 1 prior to alcohol administration and on day 5. Note that because participants are supervised 24-hours a day when they reside as inpatients, a urine pregnancy test is planned on day 7;
10. Able to provide proof of age and identity (includes providing full name and date of birth).

Exclusion Criteria:

1. DSM-5 criteria for substance use disorders other than alcohol or nicotine or test positive for prescription or illegal substances. With regard to marijuana/THC, an individual must test negative at intake (Day 1/baseline). If an individual tests positive, they will be given a grace period where they will have the opportunity to return and test negative prior to being enrolled;
2. Be pregnant or nursing;
3. Be receiving HRT where their dose has not been stable for a minimum of 3 months;
4. To reduce variability in the magnitude of drug-drug interactions (DDIs), use of concomitant medications (except birth control pills) or OTC medications should be excluded for a sufficient time before subject enrollment (at least 14 days or 5 half-lives [whichever is longer]) and for the entire duration of the study. These items should be excluded for a longer time period if the DDI mechanism is induction or time-dependent inhibition. Concomitant medication use includes any prescription, over-the-counter medications or dietary/herbal/nutritional supplements;
5. Be receiving any non-pharmacotherapy treatments or procedures for which there are precautions for taking concomitantly with PT150 and/or those that might interfere with the study;
6. Have neurological or psychiatric disorders other than AUD;
7. History of suicide attempts and/or current suicidal ideation/plan;
8. Have evidence of untreated or unstable medical illness including: cardiovascular, neuroendocrine, autoimmune, renal, hepatic, or active HIV+, AIDS infection;
9. Have a history of medically adverse reactions to alcohol (e.g., loss of consciousness (LOC), chest pain, or epileptic seizure) or major alcohol-related medical complications requiring hospitalization (i.e. hepatitis or pancreatitis);
10. Have contraindication(s) to take the study medications such as renal or hepatic impairment, congenital metabolic disorders, or hypersensitivity to study medication class (i.e., glucocorticoid antagonists);
11. Have past brain injury/head trauma with current symptoms (e.g. not photophobic, dizziness, etc.) or past report of LOC for >30 minutes and/or have been blast-exposed or had LOC of >1 minute and current post-concussive symptoms;
12. Self-report more than thirty days' abstinence from alcohol during the three months prior to enrollment/consent;
13. Current signs of violence or aggression assessed as part of the consent process;
14. Participation in a pharmaceutical trial or exposure to investigational drugs within 1 month of the screening visit;
15. Be currently seeking treatment for AUD;
16. Have any other illness, condition, or use medications (psychotropic or antiretroviral), which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of the study;
17. A history of adrenal insufficiency or a baseline plasma cortisol level of ≤ 5mcg/dL;
18. A baseline cortisol of > 5 mcg/dL BUT a post-ACTH stimulation cortisol of <18 mcg/dL;
19. Have been treated with any form of corticosteroid in the past 30 days;
20. Have a history of endometrial hyperplasia, endometrial cancer, uterine polyps, or unexplained vaginal bleeding;
21. Have potassium levels below the normal reference range;
22. Men taking testosterone replacement therapy;
23. Men or women currently interested in fertility;
24. Have underlying inflammatory or auto-immune disorders;
25. Have elevated thyroid stimulating hormone (TSH) levels;
26. Have diabetes.