Alcohol Drinking, Alcohol Use Disorder, Alcohol Use Disorder (AUD)
Conditions
Brief summary
The primary objective of this study is to evaluate the effects of ASP8062, 25 mg once a day and matched placebo, on alcohol cue-elicited alcohol craving during a human laboratory paradigm after 2 weeks of daily dosing among subjects with moderate to severe alcohol use disorder (AUD) as confirmed by the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5™). Secondary objectives include evaluation of ASP8062, 25 mg once a day, and matched placebo on reduction of alcohol consumption, alcohol craving, cigarette smoking (among smokers), mood, sleep, alcohol use negative consequences, study retention, and safety and tolerability throughout the last 4 weeks of the treatment phase of the study.
Interventions
DRUGASP8062
ASP8062 is a novel compound with positive allosteric modulator (PAM) activity on the γ-aminobutyric acid type B (GABAB) receptor, 25 mg, 1 x per day for 6 weeks
DRUGPlacebo
1 x per day for 6 weeks
Sponsors
Astellas Pharma Inc
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be at least 21 years of age. 2. Meet the DSM-5 criteria for AUD of at least moderate severity. 3. Be seeking treatment for AUD and desire a reduction or cessation of drinking. 4. Be able to verbalize an understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, able to understand written and oral instructions in English and able to complete the questionnaires required by the protocol. 5. Agree (if the subject is female and of child bearing potential) to use at least one of the following methods of birth control to at least 30 days post the last dose of study drug, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal (one year): 1. oral contraceptives, 2. contraceptive sponge, 3. patch, 4. double barrier (diaphragm/spermicidal or condom/spermicidal), 5. intrauterine contraceptive system, 6. etonogestrel implant, 7. medroxyprogesterone acetate contraceptive injection, 8. true abstinence: when this is in line with the preferred and usual lifestyle of the participant, 9. and/or hormonal vaginal contraceptive ring. 6. Agree (if female) to not donate ova for at least 30 days following the last ASP8062 administration. 7. Agree (if male) to use acceptable methods of contraception if the male participant's partner could become pregnant from the time of the first administration of the study drug until 90 days following the final administration of the study drug. One of the following acceptable methods of contraception must be utilized: 1. surgical sterilization (vasectomy); 2. the participant's female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or sub dermal implants (commenced at least 14 days prior to study drug administration to the male participant) 3. the participant's female partner uses a medically prescribed topically applied transdermal contraceptive patch (commenced at least 14 days prior to study drug administration to the male participant); 4. the participant's female partner has undergone tubal ligation (female sterilization) or is postmenopausal (one year); 5. the participant's female partner has undergone placement of an intrauterine device or intrauterine system; and, 6. true abstinence: when this is in line with the preferred and usual lifestyle of the participant. 8. Agree (if male) to refrain from sperm donation from the randomization visit to at least 90 days after the last dose of study drug. 9. Be able to take oral medication and be willing to adhere to the medication regimen. 10. Complete all assessments required at screening and baseline. 11. Have a place to live in the 2 weeks prior to randomization and not be at risk that s/he will lose his/her housing in the next 2 months. Not anticipate any significant problems with transportation arrangements or available time to travel to the study site over the next 2 months. 12. Not have any unresolved legal problems that could jeopardize continuation or completion of the study. 13. Provide contact information of someone, such as a family member, spouse, or significant other, who may be able to contact the subject in case of a missed clinic appointment. 14. Have a BAC by breathalyzer equal to 0.000 when s/he signed the informed consent document. 15. If taking a medication for depression or anxiety, must have been taking a stable dose in the 2-months prior to randomization and plan to continue during the study. This includes drugs such as the following: 1. Selective serotonin reuptake inhibitors (SSRIs) 2. Dual uptake inhibitors 3. Serotonin-norepinephrine reuptake inhibitors (SNRIs) 4. Tricyclic antidepressants 16. Be someone who in the opinion of the investigator would be expected to complete the study protocol. 17. Agree to the schedule of visits, verbally acknowledge that s/he will be able to attend each scheduled visit, participate in phone visits and that s/he does not have any already scheduled events or a job that may substantially interfere with study participation. 18. Be willing to use a smartphone's video capability to record daily oral ingestion of tablets for the entire 6-week treatment period (subject's own smartphone or one provided by AiCure). 19. Have sitting (3 to 5 minutes) vital signs at the screening visit within the following limits: 1. Systolic blood pressure 90 to 140 mmHg 2. Diastolic blood pressure of 50 to 90 mmHg 3. Heart rate of 40 to 90 beats per minute
Exclusion criteria
1. Current (past 12 months) substance use disorder of at least moderate severity (4 or more criteria) for any psychoactive substance other than alcohol and nicotine, including sedatives and hypnotics, or cocaine use disorder of any severity as defined by DSM-5 criteria. 2. Be mandated by the court to obtain treatment for alcohol-dependence, or has probation or parole requirements that might interfere with study participation. 3. Be anyone who in the opinion of the investigator could not be safely withdrawn from alcohol without medical detoxification. 4. Have any of the following, based on DSM-5 criteria as assessed using theMINI: 1. Current or lifetime diagnosis of psychotic disorders, 2. Current bipolar disorder, 3. Current major depressive episode, 4. Current (past 3 months) eating disorder (anorexia or bulimia), or 5. Within past year diagnosis of panic disorder with or without agoraphobia. Contact site for additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Craving | Week 3 | Strength of alcohol craving Visual Analogue Scale (VAS) score; min=0, max=20; higher scores = more craving (worse outcome) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Abstinent From Alcohol | Weeks 3 to 6 of the treatment phase | Number of subjects that have not drank alcohol during Weeks 3 to 6 of the treatment phase. |
| WHO 1-level Decrease in Alcohol Consumption | Weeks 3 to 6 of the treatment phase | The number of subjects experiencing at least a 1-level decrease in World Health Organization (WHO) levels of alcohol consumption from the level at baseline (the period including the 28 days before screening) to the level during Weeks 3 to 6 of the treatment phase. The WHO levels of average alcohol consumption per day are as follows: Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g where 14g = 1 SDU (WHO-2000). In computing the WHO alcohol consumption level, average drinks per day were used, computed as the sum of all drinks in the 28 day period divided by the number of days with non-missing drinking data in that period. Abstinent subjects were included in a separate Abstinent category. |
| WHO 2-level Decrease in Alcohol Consumption | Weeks 3 to 6 of the treatment phase. | The number of subjects experiencing at least a 2-level decrease in World Health Organization (WHO) levels of alcohol consumption from the level at baseline (the period including the 28 days before screening) to the level during Weeks 3 to 6 of the treatment phase. The WHO levels of average alcohol consumption per day are as follows: Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g where 14g = 1 SDU (WHO-2000). In computing the WHO alcohol consumption level, average drinks per day were used, computed as the sum of all drinks in the 28 day period divided by the number of days with non-missing drinking data in that period. Abstinent subjects were included in a separate Abstinent category. |
| Percentage of Days Abstinent | Weeks 3 to 6 of the treatment phase | The percentage of days abstinent from drinking alcohol |
| Percentage of Heavy Drinking Days | Weeks 3 to 6 of the treatment phase | Percentage of heavy drinking days where a heavy drinking day is 4 or more drinks on a day for women or 5 or more drinks on a day for men. |
| Drinks Per Week | Weeks 3 to 6 of the treatment phase | The number of drinks consumed per week |
| Number of Subjects With no Heavy Drinking Days | Weeks 3 to 6 of the treatment phase | Number of subjects that have no heavy drinking days during weeks 3 to 6 of the treatment phase. A heavy drinking day is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men. |
| Penn Alcohol Craving Scale (PACS) | Weeks 3 to 6 during the treatment phase, averaged | The amount of craving; higher numbers indicate more craving. There are 5 items each on a 0 to 6 scale. Items are summed to get to the total craving, resulting in scores having a min=0 and max=30. |
| Pittsburgh Sleep Quality Index (PSQI) | Weeks 4 & 6 of the treatment phase, averaged | A measure of sleep quality; the PSQI includes a scoring key for calculating a patient's seven subscores, each of which can range from 0 to 3. The subscores are tallied, yielding a global score that can range from 0 to 21. A global score of 5 or more indicates poor sleep quality; the higher the score, the worse the quality. |
| Patient-Reported Outcomes Measurement Information System (PROMIS) Alcohol Related Negative Consequences | Week 6 of the treatment phase | A measure of alcohol-related negative consequences. There are 7 items scored on a 1 to 7 scale (a higher score indicative greater frequency of negative consequences). The items are summed and converted to a T-score to create a total score. The T-scores range from 0 to 100 (the population mean = 50 and standard deviation = 10). Higher T-scores are indicative of more negative consequences (worse outcome). |
| Profile of Mood States (POMS) Total Disturbance | Weeks 4 & 6 of the treatment phase, averaged | A measure of total mood disturbance. Total mood disturbance is the sum of depression, anger, fatigue, confusion, and tension subscales subtracting the vigor subscale items. The range of possible scores is from -32 to 200 with higher scores indicating greater mood disturbance. |
| Cigarettes Smoked Per Day (Among Smokers) | Weeks 3 to 6 of the treatment phase | The number of cigarettes smoked per day, computed among individuals who smoked at baseline |
| Drinks Per Drinking Day | Weeks 3 to 6 of the treatment phase | The number of drinks consumed on days where participants drank |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ASP8062 (25 mg Once Daily) ASP8062: ASP8062 is a novel compound with positive allosteric modulator (PAM) activity on the γ-aminobutyric acid type B (GABAB) receptor, 25 mg, 1 x per day for 6 weeks | 28 |
| Matching Placebo Placebo: 1 x per day for 6 weeks | 26 |
| Total | 54 |
Baseline characteristics
| Characteristic | ASP8062 (25 mg Once Daily) | Matching Placebo | Total |
|---|---|---|---|
| Age, Continuous | 42.4 years STANDARD_DEVIATION 9.8 | 45.4 years STANDARD_DEVIATION 10 | 43.8 years STANDARD_DEVIATION 9.9 |
| Drinks per week | 53.5 Standard drinks of alcohol/week STANDARD_DEVIATION 22.1 | 52.3 Standard drinks of alcohol/week STANDARD_DEVIATION 20.1 | 52.9 Standard drinks of alcohol/week STANDARD_DEVIATION 21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 18 Participants | 20 Participants | 38 Participants |
| Region of Enrollment United States | 28 participants | 26 participants | 54 participants |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 16 Participants | 18 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 24 / 30 | 22 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Alcohol Craving
Strength of alcohol craving Visual Analogue Scale (VAS) score; min=0, max=20; higher scores = more craving (worse outcome)
Time frame: Week 3
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Alcohol Craving | 6.44 score on a scale | Standard Error 1.09 |
| Matching Placebo | Alcohol Craving | 6.26 score on a scale | Standard Error 1.13 |
p-value: 0.784ANCOVA
Secondary
Cigarettes Smoked Per Day (Among Smokers)
The number of cigarettes smoked per day, computed among individuals who smoked at baseline
Time frame: Weeks 3 to 6 of the treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Cigarettes Smoked Per Day (Among Smokers) | 10.3 cigarettes smoked per day | Standard Error 1.2 |
| Matching Placebo | Cigarettes Smoked Per Day (Among Smokers) | 10.7 cigarettes smoked per day | Standard Error 2 |
Secondary
Drinks Per Drinking Day
The number of drinks consumed on days where participants drank
Time frame: Weeks 3 to 6 of the treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Drinks Per Drinking Day | 5.7 standard drinks of alcohol/drinking day | Standard Error 0.5 |
| Matching Placebo | Drinks Per Drinking Day | 5.5 standard drinks of alcohol/drinking day | Standard Error 0.5 |
Secondary
Drinks Per Week
The number of drinks consumed per week
Time frame: Weeks 3 to 6 of the treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Drinks Per Week | 28.2 standard drinks of alcohol/week | Standard Error 4 |
| Matching Placebo | Drinks Per Week | 23.7 standard drinks of alcohol/week | Standard Error 4.1 |
Secondary
Number of Subjects Abstinent From Alcohol
Number of subjects that have not drank alcohol during Weeks 3 to 6 of the treatment phase.
Time frame: Weeks 3 to 6 of the treatment phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASP8062 (25 mg Once Daily) | Number of Subjects Abstinent From Alcohol | 0 Participants |
| Matching Placebo | Number of Subjects Abstinent From Alcohol | 1 Participants |
Secondary
Number of Subjects With no Heavy Drinking Days
Number of subjects that have no heavy drinking days during weeks 3 to 6 of the treatment phase. A heavy drinking day is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men.
Time frame: Weeks 3 to 6 of the treatment phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASP8062 (25 mg Once Daily) | Number of Subjects With no Heavy Drinking Days | 2 Participants |
| Matching Placebo | Number of Subjects With no Heavy Drinking Days | 1 Participants |
Secondary
Patient-Reported Outcomes Measurement Information System (PROMIS) Alcohol Related Negative Consequences
A measure of alcohol-related negative consequences. There are 7 items scored on a 1 to 7 scale (a higher score indicative greater frequency of negative consequences). The items are summed and converted to a T-score to create a total score. The T-scores range from 0 to 100 (the population mean = 50 and standard deviation = 10). Higher T-scores are indicative of more negative consequences (worse outcome).
Time frame: Week 6 of the treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Patient-Reported Outcomes Measurement Information System (PROMIS) Alcohol Related Negative Consequences | 50.2 T-score | Standard Error 1 |
| Matching Placebo | Patient-Reported Outcomes Measurement Information System (PROMIS) Alcohol Related Negative Consequences | 47.8 T-score | Standard Error 1.1 |
Secondary
Penn Alcohol Craving Scale (PACS)
The amount of craving; higher numbers indicate more craving. There are 5 items each on a 0 to 6 scale. Items are summed to get to the total craving, resulting in scores having a min=0 and max=30.
Time frame: Weeks 3 to 6 during the treatment phase, averaged
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Penn Alcohol Craving Scale (PACS) | 13.5 score on a scale | Standard Error 0.9 |
| Matching Placebo | Penn Alcohol Craving Scale (PACS) | 13.0 score on a scale | Standard Error 1 |
Secondary
Percentage of Days Abstinent
The percentage of days abstinent from drinking alcohol
Time frame: Weeks 3 to 6 of the treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Percentage of Days Abstinent | 29.9 percentage of days abstinent | Standard Error 5.4 |
| Matching Placebo | Percentage of Days Abstinent | 39.3 percentage of days abstinent | Standard Error 5.6 |
Secondary
Percentage of Heavy Drinking Days
Percentage of heavy drinking days where a heavy drinking day is 4 or more drinks on a day for women or 5 or more drinks on a day for men.
Time frame: Weeks 3 to 6 of the treatment phase
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Percentage of Heavy Drinking Days | 42.4 percentage of heavy drinking days | Standard Error 6.1 |
| Matching Placebo | Percentage of Heavy Drinking Days | 35.9 percentage of heavy drinking days | Standard Error 6.3 |
Secondary
Pittsburgh Sleep Quality Index (PSQI)
A measure of sleep quality; the PSQI includes a scoring key for calculating a patient's seven subscores, each of which can range from 0 to 3. The subscores are tallied, yielding a global score that can range from 0 to 21. A global score of 5 or more indicates poor sleep quality; the higher the score, the worse the quality.
Time frame: Weeks 4 & 6 of the treatment phase, averaged
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Pittsburgh Sleep Quality Index (PSQI) | 5.7 score on a scale | Standard Error 0.4 |
| Matching Placebo | Pittsburgh Sleep Quality Index (PSQI) | 6.1 score on a scale | Standard Error 0.4 |
Secondary
Profile of Mood States (POMS) Total Disturbance
A measure of total mood disturbance. Total mood disturbance is the sum of depression, anger, fatigue, confusion, and tension subscales subtracting the vigor subscale items. The range of possible scores is from -32 to 200 with higher scores indicating greater mood disturbance.
Time frame: Weeks 4 & 6 of the treatment phase, averaged
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASP8062 (25 mg Once Daily) | Profile of Mood States (POMS) Total Disturbance | 5.0 score on a scale | Standard Error 3.6 |
| Matching Placebo | Profile of Mood States (POMS) Total Disturbance | 0.5 score on a scale | Standard Error 3.8 |
Secondary
WHO 1-level Decrease in Alcohol Consumption
The number of subjects experiencing at least a 1-level decrease in World Health Organization (WHO) levels of alcohol consumption from the level at baseline (the period including the 28 days before screening) to the level during Weeks 3 to 6 of the treatment phase. The WHO levels of average alcohol consumption per day are as follows: Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g where 14g = 1 SDU (WHO-2000). In computing the WHO alcohol consumption level, average drinks per day were used, computed as the sum of all drinks in the 28 day period divided by the number of days with non-missing drinking data in that period. Abstinent subjects were included in a separate Abstinent category.
Time frame: Weeks 3 to 6 of the treatment phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASP8062 (25 mg Once Daily) | WHO 1-level Decrease in Alcohol Consumption | 19 Participants |
| Matching Placebo | WHO 1-level Decrease in Alcohol Consumption | 18 Participants |
Secondary
WHO 2-level Decrease in Alcohol Consumption
The number of subjects experiencing at least a 2-level decrease in World Health Organization (WHO) levels of alcohol consumption from the level at baseline (the period including the 28 days before screening) to the level during Weeks 3 to 6 of the treatment phase. The WHO levels of average alcohol consumption per day are as follows: Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g where 14g = 1 SDU (WHO-2000). In computing the WHO alcohol consumption level, average drinks per day were used, computed as the sum of all drinks in the 28 day period divided by the number of days with non-missing drinking data in that period. Abstinent subjects were included in a separate Abstinent category.
Time frame: Weeks 3 to 6 of the treatment phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASP8062 (25 mg Once Daily) | WHO 2-level Decrease in Alcohol Consumption | 8 Participants |
| Matching Placebo | WHO 2-level Decrease in Alcohol Consumption | 11 Participants |