Potential Treatment for Alcohol Dependence-Alcohol Interaction Clinical Trial
Official title:
PT150 (Formerly ORG34517) as a Potential Treatment for Alcohol Dependence-Alcohol Interaction Study
| Verified date | December 2023 |
| Source | Pop Test Oncology LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this clinical study is to assess pharmacokinetic interactions between ethanol (EtOH) and PT150 (900 mg qd) in non-treatment-seeking alcohol-experienced volunteers-(to include military service members, veterans and/or civilians).
| Status | Completed |
| Enrollment | 10 |
| Est. completion date | October 27, 2023 |
| Est. primary completion date | October 27, 2023 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 21 Years to 64 Years |
| Eligibility | 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 the last dose of study drug has been given, 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 9; 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, nicotine, or marijuana or test positive for prescription or illegal substances other than THC. With regard to marijuana/THC, an individual must agree to abstain from marijuana/THC use three days prior to intake (Day 1/baseline); 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 hormonal birth control) 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 or SUD for THC; 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 within the last 10 years 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 Type I diabetes. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Michael E. DeBakey Veterans Affairs Medical Center | Houston | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Pop Test Oncology LLC | Baylor College of Medicine, Congressionally Directed Medical Research Programs, Michael E. DeBakey VA Medical Center, Pharmacotherapies for Alcohol and Substance Use Disorders Alliance |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Difference in maximum concentration of PT150 (CmaxPT150) | Estimates of maximum concentration (Cmax) of PT150 will be calculated and compared from PT150 steady state alone (days 6-7) to concurrent steady state of PT150 with ethanol exposure (days 7-9). | from the PT150 blood draws (days 6-7) to the PT150 with concurrent ethanol blood draws (days 7-9) | |
| Primary | Difference in time of maximum concentration of PT150 (tmaxPT150) | Estimates of time of maximum concentration (Tmax) of PT150 will be calculated and compared from PT150 steady state alone (days 6-7) to concurrent steady state of PT150 with ethanol exposure (days 7-9). | from the PT150 blood draws (days 6-7) to the PT150 with concurrent ethanol blood draws (days 7-9) | |
| Primary | Difference in terminal elimination half-life of PT150 (t1/2PT150) | Estimates of terminal elimination half-life (T1/2) of PT150 will be calculated and compared from PT150 steady state alone (days 6-7) to concurrent steady state of PT150 with ethanol exposure (days 7-9). | from the PT150 blood draws (days 6-7) to the PT150 with concurrent ethanol blood draws (days 7-9) | |
| Primary | Difference in area under the concentration-time curve of PT150 (AUCPT150) | Estimates of the area under the concentration curve (AUC) through 24 hours post-intervention of PT150 will be calculated and compared from PT150 steady state alone (days 6-7) to concurrent steady state of PT150 with ethanol exposure (days 7-9). | from the PT150 blood draws (days 6-7) to the PT150 with concurrent ethanol blood draws (days 7-9) | |
| Secondary | Difference in the maximum concentration of ethanol (CmaxEtOH) | Estimates of maximum concentration (Cmax) of ethanol will be calculated and compared from ethanol alone (days 1-2) to concurrent steady state of PT150 with ethanol exposure (days 7-9). | from the ethanol alone blood draws (days 1-2) to the PT150 with concurrent ethanol blood draws (days 7-9) | |
| Secondary | Difference in time of maximum concentration of ethanol (tmaxEtOH) | Estimates of time of maximum concentration (Tmax) of ethanol will be calculated and compared from ethanol alone (days 1-2) to concurrent steady state of PT150 with ethanol exposure (days 7-9). | from the ethanol alone blood draws (days 1-2) to the PT150 with concurrent ethanol blood draws (days 7-9) | |
| Secondary | Difference in terminal elimination half-life of ethanol (t1/2EtOH) | Estimates of terminal elimination half-life (T1/2) of ethanol will be calculated and compared from ethanol alone (days 1-2) to concurrent steady state of PT150 with ethanol exposure (days 7-9). | from the ethanol alone blood draws (days 1-2) to the PT150 with concurrent ethanol blood draws (days 7-9) | |
| Secondary | Difference in the area under the concentration-time curve of ethanol (AUCEtOH) | Estimates of the area under the concentration curve (AUC) through 24 hours post-intervention of ethanol will be calculated and compared from ethanol alone (days 1-2) to concurrent steady state of PT150 with ethanol exposure (days 7-9). | from the ethanol alone blood draws (days 1-2) to the PT150 with concurrent ethanol blood draws (days 7-9) | |
| Secondary | Difference in the number and severity of adverse events | Difference in the overall number and proportion of adverse events compared among ethanol alone (days 1-2), PT150 alone (days 2-7), and PT150 with ethanol exposure (days 7-9). Comparisons will also be stratified by severity of adverse events. | Adverse events are reported throughout the study, from enrollment to study completion | |
| Secondary | Difference in heart rate | Difference in heart rate compared among ethanol alone (days 1-2), PT150 alone (days 6-7), and PT150 with ethanol exposure (days 7-9). | Heart rate is collected one time after the serial blood draws have been completed for each of ethanol alone (day 2), PT150 alone (day 7), and PT150 with ethanol exposure (day 9). | |
| Secondary | Difference in systolic blood pressure | Difference in systolic blood pressure compared among ethanol alone (days 1-2), PT150 alone (days 6-7), and PT150 with ethanol exposure (days 7-9). | Systolic blood pressure is collected one time after the serial blood draws have been completed for each of ethanol alone (day 2), PT150 alone (day 7), and PT150 with ethanol exposure (day 9). | |
| Secondary | Difference in diastolic blood pressure | Difference in diastolic blood pressure compared among ethanol alone (days 1-2), PT150 alone (days 6-7), and PT150 with ethanol exposure (days 7-9). | Diastolic blood pressure is collected one time after the serial blood draws have been completed for each of ethanol alone (day 2), PT150 alone (day 7), and PT150 with ethanol exposure (day 9). | |
| Secondary | Change in severity of alcohol withdrawal symptom severity as measured on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) | Change in CIWA-Ar total score from baseline (pre-PT150 exposure) to all post-PT150 exposure measurements. | The CIWA-Ar assessment is completed one time on day 1 prior to ethanol and PT150 exposure, followed by measurements on days 5, 6, 7, 8, and 9 (all post-PT150 exposure measurements). | |
| Secondary | Change in ECG abnormalities | Change in ECG abnormalities from baseline (pre-PT150 exposure) to all post-PT150 exposure measurements. | An ECG measurement is taken once on day 1 prior to ethanol and PT150 exposure, followed by measurements on days 2, 5, 6, 7, 8, and 9 (all post-PT150 exposure measurements). |