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

NCT04331288 | Completed Phase 1 FDA Drug

• 2 other identifiers: AS140026-A3cW81XWH-15-2-0077
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Potential Treatment for Alcohol Dependence-Alcohol Interaction

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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)

• 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)

• 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)

• 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 Outcomes (10)

• Difference in the maximum concentration of ethanol (CmaxEtOH)

  from the ethanol alone blood draws (days 1-2) to the PT150 with concurrent ethanol blood draws (days 7-9)

• Difference in time of maximum concentration of ethanol (tmaxEtOH)

  from the ethanol alone blood draws (days 1-2) to the PT150 with concurrent ethanol blood draws (days 7-9)

• Difference in terminal elimination half-life of ethanol (t1/2EtOH)

  from the ethanol alone blood draws (days 1-2) to the PT150 with concurrent ethanol blood draws (days 7-9)

• Difference in the area under the concentration-time curve of ethanol (AUCEtOH)

  from the ethanol alone blood draws (days 1-2) to the PT150 with concurrent ethanol blood draws (days 7-9)

• Difference in the number and severity of adverse events

  Adverse events are reported throughout the study, from enrollment to study completion

Study Arms (1)

PT150 with alcohol consumption

EXPERIMENTAL

Study drug to be administered as a single, fixed dose over a 5-day period. An alcohol challenge will be completed on day 1 (pre-treatment) followed by blood draws over a 24-hour period. PT150 dosing will begin on study day 2 and continue until steady state is reached on day 6, at which point blood draws will occur over a 24-hour period. On day 7, after PT150 steady state has been achieved, an alcohol challenge will be completed followed by blood draws over a 40-hour period.

Drug: PT150; Other: Beverage

Interventions

PT150 DRUG

Intervention 1 includes PT150 with alcohol consumption

Also known as: Formerly ORG34517

PT150 with alcohol consumption

Beverage OTHER

The alcohol beverage will be prepared by an in-house pharmacist at the MEDVAMC in a volume of 450 ml for a 70 kg individual and adjusted for body weight by varying the volume. Alcohol will be administered in a concentration of 16% alcohol (Everclear, St. Louis, MO) by volume in juice or another flavored beverage. Participants will be allowed 30 minutes to consume the beverages.

Also known as: Ethanol beverage

PT150 with alcohol consumption

Eligibility Criteria

• Age: 21 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide signed and dated informed consent form;
• Male or female, aged 21-64;
• 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;
• 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);
• 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;
• 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;
• Must be willing to comply with all study procedures and be available for the duration of the study;
• 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;
• 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;
• Able to provide proof of age and identity (includes providing full name and date of birth).

You may not qualify if:

• 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);
• Be pregnant or nursing;
• Be receiving HRT where their dose has not been stable for a minimum of 3 months;
• 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;
• 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;
• Have neurological or psychiatric disorders other than AUD or SUD for THC;
• History of suicide attempts and/or current suicidal ideation/plan;
• Have evidence of untreated or unstable medical illness including: cardiovascular, neuroendocrine, autoimmune, renal, hepatic, or active HIV+, AIDS infection;
• 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);
• 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);
• 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;
• Self-report more than thirty days' abstinence from alcohol during the three months prior to enrollment/consent;
• Current signs of violence or aggression assessed as part of the consent process;
• Participation in a pharmaceutical trial or exposure to investigational drugs within 1 month of the screening visit;
• Be currently seeking treatment for AUD;

Sponsors & Collaborators

• Pop Test Oncology LLC: lead
• Pharmacotherapies for Alcohol and Substance Use Disorders Alliance: collaborator
• Congressionally Directed Medical Research Programs: collaborator
• Michael E. DeBakey VA Medical Center: collaborator
• Baylor College of Medicine: collaborator

Study Sites (1)

Michael E. DeBakey Veterans Affairs Medical Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Alcoholism; Alcohol Drinking; Stress Disorders, Post-Traumatic; Substance-Related Disorders

Interventions

(11R,13S,17S)-11-(1,3-benzodioxol-5-yl)-17-hydroxy-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta(a)phenanthren-3-one; Beverages

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Drinking Behavior; Behavior; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Intervention Hierarchy (Ancestors)

Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Christopher Verrico, PhD

  Michael E. DeBakey Veterans Affairs Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 2, 2020
• Study Start: November 1, 2021
• Primary Completion: October 27, 2023
• Study Completion: October 27, 2023
• Last Updated: December 4, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

US (1)