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| ID | Type | Description | Link |
|---|---|---|---|
| W81XWH-15-2-0077 | Other Identifier | RTI International |
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| Name | Class |
|---|---|
| Pharmacotherapies for Alcohol and Substance Use Disorders Alliance | OTHER |
| Congressionally Directed Medical Research Programs | FED |
| Michael E. DeBakey VA Medical Center | FED |
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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.
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 (to include military service members, veterans and/or civilians). Study duration will be six days; in-house; Day 0 (admission) until day six (final study day and day of discharge). Participants will undergo two alcohol challenges on day 1 separated by 4 hours (one with alcohol, 0.8g/kg; 16% ethanol by volume, and one with placebo beverage, 1% ethanol 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 (e.g., vital signs, electrocardiogram), subjective and psychometric effects (e.g., mood, urge, craving, stimulant and sedative effects), and breath alcohol levels (BAL) will be obtained after the alcohol challenges. On day six, an electrocardiogram (ECG) will be performed, adverse events (AEs) and symptom checklist will be collected, including symptoms of adrenal insufficiency (AI), and a blood draw for electrolyte levels and cortisol will be collected in the morning followed by breakfast and discharge if laboratory tests are within normal ranges. All serious adverse events will be followed clinically until resolved or clinically stable. Pharmacodynamic and safety endpoints will be assessed during the alcohol challenge prior to, and after 5 days of PT150 treatment, when PT150 has reached steady state. For females, a follow-up visit will be scheduled to occur at least 14 days after the final dose of PT150 is administered to ensure pregnancy does not occur. The objectives of the study are to compare pharmacodynamics and safety endpoints following an alcohol challenge prior to and concurrent with PT150. Given available pre-clinical and clinical evidence for the salutatory effect of glucocorticoid receptor (GR) antagonists on alcohol withdrawal, it was hypothesized that PT150 will not significantly alter pharmacodynamic measures and will be safe and well-tolerated under conditions of alcohol consumption.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PT150 | Drug | Intervention 1 includes PT150 with alcohol consumption |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive Assessment - Hopkins Verbal Learning Task-Revised (HLVT-R) Total Recall Score | . Change in cognitive effects, measured by the HVLT-R Total Recall scores, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge day 5 (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
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Inclusion Criteria: - Provide signed and dated informed consent;
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Michael E. DeBakey Veterans Affairs Medical Center | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26143299 | Background | 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. | |
| 26121746 |
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Data will be shared with a registry per the data sharing plans of the Consortium.
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D000428 | Alcohol Drinking |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000727867 | (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 |
| D001628 | Beverages |
| ID | Term |
|---|---|
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
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| Baylor College of Medicine |
| OTHER |
| University of California, San Diego | OTHER |
Apart from the Research Pharmacists, all others engaged with this study (participants and study team) will be masked to alcohol challenge order.
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| 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. |
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| 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) |
| Cognitive Assessment - Hopkins Verbal Learning Task-Revised (HLVT-R) Delayed Recall Score |
. Change in cognitive effects, measured by the HVLT-R Delayed Recall scores, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge day 5 (post-treatment). |
| from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Hopkins Verbal Learning Task-Revised (HLVT-R) Percent Retained Score | . Change in cognitive effects, measured by the HVLT-R Percent Retained scores, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge day 5 (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Hopkins Verbal Learning Task-Revised (HLVT-R) Discrimination Index Score | . Change in cognitive effects, measured by the HVLT-R Discrimination Index scores, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge day 5 (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Dual n-Back (DNB) auditory trial accuracy score | Change in cognitive effects, measured by the DNB auditory trial accuracy scores, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Dual n-Back (DNB) visual trial accuracy score | Change in cognitive effects, measured by the DNB visual trial accuracy scores, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Dual n-Back (DNB) auditory reaction time | Change in cognitive effects, measured by the DNB auditory reaction times, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Dual n-Back (DNB) visual reaction time | Change in cognitive effects, measured by the DNB visual reaction time, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Continuous Performance Task-2 (CPT) errors of commission score | Change in cognitive effects, measured by the CPT errors of commission score, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Continuous Performance Task-2 (CPT) errors of ommission score | Change in cognitive effects, measured by the CPT errors of ommission score, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Continuous Performance Task-2 (CPT) errors of perseveration score | Change in cognitive effects, measured by the CPT errors of perseveration score, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Cognitive Assessment - Continuous Performance Task-2 (CPT) reaction time | Change in cognitive effects, measured by the CPT reaction time, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Psychomotor Assessment - One Legged Stand (OLS) | Change in psychomotor effects, measured by the OLS, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| Psychomotor Assessment - Walk and Turn (WAT) | Change in psychomotor effects, measured by the WAT, will be compared between the day 1 alcohol challenge (pre-treatment) and the day 5 alcohol challenge (post-treatment). | from pre-treatment (day 1) to post-treatment (day 5) |
| 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. |
| 33972573 | Derived | 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. |
| D004327 | Drinking Behavior |
| D001519 | Behavior |