Clinical Trial to Evaluate the Safety of PT150 (Formerly ORG34517) When it is Taken Concurrently With Alcohol

NCT03548714 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: AS140026-A3.bW81XWH-15-2-0077
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the clinical study is to compare pharmacodynamic and safety endpoints following an alcohol challenge prior to and concurrent with PT150 (study drug) treatment.

Conditions

Alcohol Dependence; Alcohol Interaction

Keywords

Alcohol; Alcoholic; Alcoholism; Alcohol abuse; Alcohol interaction; Alcohol Use Disorder; Alcohol use; Alcohol dependence; Alcohol dependent; Ethanol abuse; Ethanol use

Outcome Measures

Primary Outcomes (17)

• Change in Breath-alcohol levels (BALs) - Cmax

  Mean estimates of Cmax (observed maximum concentration after alcohol challenge) will be calculated and compared from post-alcohol challenge pre-treatment (day 1) to post alcohol challenge with concurrent treatment (day 5).

  from post-alcohol challenge pre-treatment (day 1)to post alcohol with concurrent intreatment (day 5)

• Change in Breath-alcohol levels (BALs) - Tmax

  Mean estimates of Tmax (time of occurrence of Cmax) will be calculated and compared from post-alcohol challenge pre-treatment (day 1) to post alcohol challenge with concurrent treatment (day 5).

  from post-alcohol challenge pre-treatment (day 1)to post alcohol with concurrent treatment (day 5)

• Change in Breath-alcohol levels (BALs) - AUC

  Mean estimates of AUC (area under the concentration curve through 2 hours post-alcohol challenge) will be calculated and compared from post-alcohol challenge pre-treatment (day 1) to post alcohol challenge with concurrent treatment (day 5).

  from post-alcohol challenge pre-treatment (day 1) to post alcohol with concurrent treatment (day 5)

• Change in blood pressure

  For each alcohol challenge on Days 1 and 5, the change in blood pressure (systolic and diastolic) is computed as the difference in blood pressure measurements taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Heart Rate (Pulse)

  For each alcohol challenge on days 1 and 5, the change in heart rate (pulse) is computed as the difference in heart rate measurements taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5).

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in ECG abnormalities

  ECG abnormalities (normal, abnormal but not clinically significant, clinically significant abnormal) will be compared between pre-treatment (baseline, day 1 AM) to post-treatment (days 1 through 6)

  from pre-treatment (baseline) to post-treatment (day 6)

• Change in Positive Affect score from the Positive and Negative Affect Schedule (PANAS)

  Positive changes in Positive Affect score indicate an increased positive affect. For each alcohol challenge on Days 1 and 5, the change in the positive affect scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Negative Affect score from the Positive and Negative Affect Schedule (PANAS)

  Negative changes in Negative Affect score indicate a decreased negative effect post-challenge. For each alcohol challenge on Days 1 and 5, the change in the negative affect scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Alcohol Urge Questionnaire (AUQ) score

  The change in AUQ score reflects the participant's thoughts and feelings about drinking, with negative score changes indicating a decrease in craving post-challenge. For each alcohol challenge on Days 1 and 5, the change in the AUQ scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Biphasic Alcohol Effects Scale (BAES) Sedative effects

  : The change in BAES sedative effects measures the sedative effects of alcohol, with a positive score change indicating an increase in sedation. For each alcohol challenge on Days 1 and 5, the change in the BAES sedative effects scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Biphasic Alcohol Effects Scale (BAES) Stimulant effects

  The change in BAES stimulant effects measures the stimulant effects of alcohol, with a positive score change indicating an increase in stimulation. For each alcohol challenge on Days 1 and 5, the change in the BAES stimulant effects scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Addiction Research Center Inventory (ARCI) score - Pentobarbital-Chlorpromazine-Alcohol Group Scale

  The Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) Scale of the ARCI assesses the subjective effects of those psychologically active drugs, with positive score changes indicating an increase in sedation. For each alcohol challenge on Days 1 and 5, the change in the ARCI PCAG scale scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Addiction Research Center Inventory (ARCI) score - Amphetamine Scale

  The Amphetamine Scale of the ARCI assesses the subjective effects of that psychologically active drug, with positive score changes indicating an increase in stimulation. For each alcohol challenge on Days 1 and 5, the change in the ARCI amphetamine scale scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Addiction Research Center Inventory (ARCI) score - Morphine-Benzedrine Group (MBG) Scale

  The Morphine-Benzedrine Group Scale of the ARCI assesses the subjective effects of those psychologically active drugs, with positive score changes indicating an increase in euphoria/mood elevation. For each alcohol challenge on Days 1 and 5, the change in the ARCI MBG scale scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Addiction Research Center Inventory (ARCI) score - LSD Scale

  The LSD Scale of the ARCI assesses the subjective effects of that psychologically active drug, with positive score changes indicating an increase in dysphoric and psychotomimetic changes. For each alcohol challenge on Days 1 and 5, the change in the ARCI LSD scale scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Change in Addiction Research Center Inventory (ARCI) score - Benzedrine Group Scale

  The Benzedrine Group Scale of the ARCI assesses the subjective effects of those psychologically active drugs, with positive score changes indicating an increase in intellectual efficiency and energy. For each alcohol challenge on Days 1 and 5, the change in the ARCI Benzedrine scale scores are computed as the difference in scores taken during the 2 hours after the alcohol challenges on days 1 and 5 and the ones collected immediately prior to that alcohol challenge. Mean changes are then calculated and compared from both post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

  from post-alcohol challenge pre-treatment (day 1) to post-alcohol challenge with concurrent treatment (day 5)

• Differences in the adverse events

  Number of adverse events on day 1 (pre-treatment) will be compared to the number of adverse events on Day 5 (post-treatment). Proportion of patients experiencing an adverse event on day 1 (pre-treatment) may also be compared to the proportion of patients experiencing an adverse event on day 5 (post-treatment).

  from pre-treatment (day 1) to post-treatment (day 5)

Secondary Outcomes (14)

• Cognitive Assessment - Hopkins Verbal Learning Task-Revised (HLVT-R) Total Recall Score

  from pre-treatment (day 1) to post-treatment (day 5)

• Cognitive Assessment - Hopkins Verbal Learning Task-Revised (HLVT-R) Delayed Recall Score

  from pre-treatment (day 1) to post-treatment (day 5)

• Cognitive Assessment - Hopkins Verbal Learning Task-Revised (HLVT-R) Percent Retained Score

  from pre-treatment (day 1) to post-treatment (day 5)

• Cognitive Assessment - Hopkins Verbal Learning Task-Revised (HLVT-R) Discrimination Index Score

  from pre-treatment (day 1) to post-treatment (day 5)

• Cognitive Assessment - Dual n-Back (DNB) auditory trial accuracy score

  from pre-treatment (day 1) to post-treatment (day 5)

Study Arms (2)

PT150 with alcohol consumption

EXPERIMENTAL

Study drug to be administered as a single, fixed dose over a 5-day period. An alcohol challenge (with ethanol or placebo beverage) will be completed on day 1 (pre-treatment), and day-5 (post-treatment), at predetermined times.

Drug: PT150

PT150 with placebo consumption

PLACEBO COMPARATOR

Study drug to be administered as a single, fixed dose over a 5-day period. An alcohol challenge (with ethanol or placebo beverage) will be completed on day 1 (pre-treatment), and day-5 (post-treatment), at predetermined times.

Other: Beverage

Interventions

PT150 DRUG

Intervention 1 includes PT150 with alcohol consumption

Also known as: Formerly ORG34517

PT150 with alcohol consumption

Beverage OTHER

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 grape Kool-Aid (Kraft Foods, Northfield, IL). Placebo will be prepared in the same manner but contain 1% alcohol to mask taste.

Also known as: Placebo drink and ethanol drink

PT150 with placebo consumption

Eligibility Criteria

• Age: 21 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• male and female, ages 21 to 64;
• must score \<10 on the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar) assessed in the context of a blood alcohol level (BAL) ≤ 0.02% to demonstrate that they do not need medical detoxification; must have blood laboratory test results within acceptable limits (normal range as noted per protocol);
• have normal vitals (heart rate 60-100 beats per minute (bpm), systolic blood pressure 90-140 millimeter of mercury (mmHg) and diastolic blood pressure 60-90 mmHg); a baseline electrocardiogram (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 judgement 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 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;
• women must provide negative urine pregnancy tests before study entry (urine), and before alcohol administrations on day 0 or 1 (serum) and on day 5 (urine);
• able to provide proof of age and identity (includes providing full name and date of birth), forms of proof as defined per protocol.

You may not qualify if:

• Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for substance use disorders other than alcohol or nicotine or test positive for prescription or illegal substances. With regard to marijuana/tetrahydrocannabinols (THC), an individual must test negative at the 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;
• pregnant or nursing;
• receiving HRT where their dose has not been stable for a minimum of 3 months;
• use of concomitant medications (except birth control pills) or other the counter (OTC) supplements for at least 14 days or 5 half-lives (whichever is longer) before the start of the study and for the entire duration of the study. Concomitant medication use includes any prescription, OTC medications, or herbal supplements;
• receiving any non-pharmacotherapy treatments or procedures for which there are precautions for taking concomitantly with PT150 and/or those that interfere with the study;
• have neurological or psychiatric disorders other than Alcohol Use Disorder (AUD);
• 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 Human Immucodeficiency Virus (HIV) +, Acquired Immune Deficiency Syndrome (AIDS) infection;
• have a history of medically adverse reactions to alcohol (e.g., loss of consciousness, 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., glucosteroid abntagonist);
• have past brain injury/head trauma with current symptoms (e.g., not photophobic, dizziness etc.) or past report of loss of consciousness (LOC) for \>30 minutes and/or have been blast-exposed or had LOC \>1 minute and current post-concussive symptoms;
• self report more than thirty days' abstinence from alcohol during the three months prior to enrollment/consent;
• current signs or violence or aggression, assessed as part of the consent process;
• a history of adrenal insufficiency or a plasma cortisol level of ≤ 5 microgram per deciliter (mcg/dl) at screening or intake;
• participation in a pharmaceutical trial or exposure to investigational drugs within 1 month of the screening visit;

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
• University of California, San Diego: collaborator

Study Sites (1)

Michael E. DeBakey Veterans Affairs Medical Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Reynolds AR, Saunders MA, Brewton HW, Winchester SR, Elgumati IS, Prendergast MA. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation. Drug Alcohol Depend. 2015 Sep 1;154:100-4. doi: 10.1016/j.drugalcdep.2015.06.018. Epub 2015 Jun 22.

  PMID: 26143299 BACKGROUND

• Vendruscolo LF, Estey D, Goodell V, Macshane LG, Logrip ML, Schlosburg JE, McGinn MA, Zamora-Martinez ER, Belanoff JK, Hunt HJ, Sanna PP, George O, Koob GF, Edwards S, Mason BJ. Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals. J Clin Invest. 2015 Aug 3;125(8):3193-7. doi: 10.1172/JCI79828. Epub 2015 Jun 29.

  PMID: 26121746 BACKGROUND

• Morice C, Baker DG, Patel MM, Nolen TL, Nowak K, Hirsch S, Kosten TR, Verrico CD. A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers. Sci Rep. 2021 May 10;11(1):9876. doi: 10.1038/s41598-021-88609-6.

  PMID: 33972573 DERIVED

MeSH Terms

Conditions

Alcoholism; Alcohol Drinking

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; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Drinking Behavior; Behavior

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Apart from the Research Pharmacists, all others engaged with this study (participants and study team) will be masked to alcohol challenge order.

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: June 7, 2018
• Study Start: September 1, 2018
• Primary Completion: July 15, 2019
• Study Completion: July 15, 2019
• Last Updated: August 22, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)