Alcohol Use Disorder, Posttraumatic Stress Disorder (PTSD)
Conditions
Keywords
Alcohol Drinking, Craving, Drinking Behavior, Prazosin, Naltrexone, Adrenergic Alpha-1 Receptor Antagonists, Adrenergic Antagonists, Adrenergic Alpha-Antagonists, mu-Opioid Receptor Antagonist, Opioid Antagonist, Alcohol Use Disorder, Posttraumatic Stress Disorder, PTSD, Alcohol Treatment, Alcohol Dependence, Pharmacology Treatment, AUD, Alcohol Abuse, Substance Use Disorder, SUD, Substance Abuse, Addiction, Alcohol Addiction, Substance Addiction, Substance Dependence
Brief summary
The purpose of this study is to evaluate whether the combination of prazosin and naltrexone will decrease alcohol cravings and drinking in individuals who have problems with alcohol and have used alcohol at risky levels compare to naltrexone and placebo (Nal/Pl), prazosin and placebo (Praz/Pl), and double-placebo (Pl/Pl). We hypothesize that those assigned to both prazosin and naltrexone would report significantly greater decreases in percent drinking days and heavy drinking days as well as significantly greater reduction in craving from pre to post-treatment than those assigned to either single medication or double-placebo. Prazosin is a medication that is approved by the U.S. Food and Drug Administration (FDA) to treat people with high blood pressure. Some studies have shown that prazosin may also decrease nightmares and improve sleep in Veterans suffering from Posttraumatic Stress Disorder (PTSD). Animal studies have consistently found that prazosin is associated with decreased alcohol consumption and that the combination of prazosin and naltrexone outperforms either medication alone. The current study is evaluating an off-label use of prazosin to determine whether it is helpful in decreasing alcohol cravings and consumption among people with alcohol problems. Off-label means that the FDA has not approved the use of prazosin for alcohol problems. Naltrexone is a medication that is FDA approved for treating alcohol problems. This study is sponsored by the Department of Defense and the Congressionally Directed Medical Research Program (DoD/CDMRP). We expect approximately 120 participants in this study, which will run over approximately 4 years. Study participants will be involved in the study for 7 weeks, or until they complete the Final Assessment.
Detailed description
In this double-blind, double-dummy, placebo-controlled study of prazosin and naltrexone, we will evaluate the combination of naltrexone and the noradrenergic medication prazosin (Nal/Praz) relative to naltrexone and placebo (Nal/Pl), prazosin and placebo (Praz/Pl), and double-placebo (Pl/Pl). Participants will undergo two craving inductions, one oriented towards relief craving and the other towards reward craving. Daily IVR (Interactive Voice Recording System) data on craving and consumption and PTSD symptomatology will be collected during the 7 days immediately following the initial assessment visit to establish a pre-medication baseline. One hundred twenty individuals with adequate IVR compliance and whose screening lab tests indicate it is safe for them to take the study medications will enter the medication phase of the study within 14 days of the initial assessment initiating prazosin/placebo as well as 50mg naltrexone/placebo treatment. Randomization will be blocked by gender, PTSD status, and desire to abstain vs. desire to cut down. Prazosin will be titrated to three times daily dosing (9 am: 4mg; 3pm: 4 mg; 9pm: 8mg) at the end of two weeks. Naltrexone will be taken once daily 50 mg/day with no titration schedule. The stable dose of both medications will continue for four more weeks and medication compliance will be evaluated through pill counts, the IVR daily monitoring, and riboflavin trace in urine analysis. On approximately day 42 participants will come into the lab for the craving inductions (there will be a two week window after day 42 in which participants may still be seen if scheduling issues arise). The order of the craving inductions will be counterbalanced, and their administration will be separated in time by 30 minutes to minimize carry over between them. Subjective responses to the craving inductions will be obtained via relief oriented craving items and reward oriented craving items from the Desire for Alcohol Questionnaire. Participants will then be assisted in returning their craving levels to baseline prior to debriefing. They will all be offered treatment referrals within the Veterans Affairs (VA) or in the community. Both prazosin and naltrexone can be safely discontinued without tapering.
Interventions
DRUGPrazosin
Prazosin Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM
DRUGNaltrexone
Naltrexone Dosing Days 1-42: 50mg @ 9PM
DRUGPlacebo (Prazosin)
Placebo Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM
DRUGPlacebo (Naltrexone)
Placebo Dosing Days 1-42: 50mg @ 9PM
Sponsors
United States Department of Defense
VA Puget Sound Health Care System
Seattle Institute for Biomedical and Clinical Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
No study staff, including the participants, will know which condition the participants are in. Only the Research Pharmacist will know the participants' conditions.
Intervention model description
Eligible participants will be randomized into one of four study conditions: Naltrexone/Prazosin (Nal/Praz), Naltrexone/Placebo (Nal/Pl), Prazosin/Placebo (Praz/Pl), and Placebo/Placebo (Pl/Pl). Randomization will be blocked by gender, PTSD status, and alcohol consumption goal (abstention vs. reduction) and will be conducted by a VA Puget Sound Research Pharmacist using randomization tables supplied by the study Principal Investigator (PI). The Research Pharmacist will have no additional contacts with the participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Veteran of the U.S. military or National Guard Reserve. 2. Current AUD by DSM-5 criteria. 3. Heavy drinking (\>14 drinks per week for females; \> 21 drinks per week for males) for at least 2 weeks in the last 3 months and some drinking during the past two weeks OR binge drinking for at least 3 days in the last month (4+ drinks for females; 5+ drinks for males). 4. At least mild alcohol craving as assessed by the Pennsylvania Alcohol Craving Scale (PACS; score \> 10) at baseline. 5. Age 18-80. 6. English fluency and literacy. 7. Trying or planning to try to cut down on or abstain from alcohol. 8. Good general medical health. 9. Capable of giving informed consent.
Exclusion criteria
1. Uncontrolled psychiatric disorder with psychotic symptoms or cognitive impairment. 2. If taking psychiatric medication, NOT on a stable dose for at least 30 days prior to randomization. 3. Any suicidal ideation in the past 7 days, plan or intent past 6 months, or any suicide attempt past year. 4. Homicidal ideation with plan and intent in the past 30 days. 5. Patient Health Questionnaire-9 (PHQ-9) endorsement of hopelessness or self-harm/SI and/or sum scale score ≥ 19. 6. Any use of prazosin or naltrexone past 30 days. 7. Currently taking disulfiram or acamprosate OR planning to take any of these medications (including prazosin or naltrexone) during the study. 8. Current moderate or severe substance use disorder (past 30 days) on any psychoactive substance other than alcohol, nicotine, or cannabis, OR use of any amphetamine or opioid-containing medications during the previous 30 days. 9. Significant acute or chronic medical illness 10. Preexisting hypotension (sys \<100) or orthostatic hypotension (systolic drop of \> 20 mmHg; after two minutes of standing, or any drop with dizziness). 11. Allergy or previous adverse reaction to naltrexone, prazosin, quinazolines, or other α-1 adrenergic blockers or use of other α -1 adrenergic blocker. 12. Women who are pregnant, breastfeeding, or of childbearing potential and not using a contraceptive method judged by the investigator to be effective. 13. Legal involvement that could interfere with study participation, including being court ordered for treatment. 14. Signs or symptoms of withdrawal at time of initial consent. 15. Any participation in an experimental drug study or any addiction study past 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD) | Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties. | PDD was calculated based on self-reported drinking history collected via Form-90. Drinking days were defined as days when participants consumed alcohol. Form-90 was completed by participants in visit 2 (baseline) and visit 8 (last visit). Form-90 collected in the baseline visit recorded participants' alcohol consumption from 90 days prior to their baseline visit until the day before their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome measures changes in PDD between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties. |
| Change in Percent Heavy Drinking Days (PHDD) (Visit 8 PHDD - Visit 2 PHDD) | Visit 2 (baseline) and Visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties. | PHDD was calculated based on self-reported drinking history collected via Form-90. Heavy drinking days were defined as days when participants consumed 4 or more drinks for females and 5 or more drinks for males. Form-90 was completed by participants in the baseline and last visit. Form-90 collected in the baseline visit recorded participants' alcohol consumption 90 days prior to their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome measures changes in PHDD between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties. |
| Change in Alcohol Craving (Visit 8 PACS - Visit 2 PACS) | Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties. | Alcohol craving was assessed in visit 2 (baseline) and the last visit (visit 8) using the Pennsylvania Alcohol Craving Scale (PACS). The PACS had 5 questions, where each question had six options presented in Likert Scales from 0 to 6, with 0 being the least and 6 being the highest possible option, thus the possible minimum and maximum values are 0 and 30, respectively. Higher scores mean higher craving. This outcome measures the change in PACS scores between visits 2 and 8 (visit 8 PACS score - visit 2 PACS score). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Drinks Per Day of Drinking (Visit 8 - Visit 2) | Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties. | Average drinks per day of drinking was calculated based on self-reported drinking history collected via Form-90. Drinking days were defined as days when participants consumed alcohol. Form-90 was completed by participants in visit 2 (baseline) and visit 8 (last visit). Form-90 collected in the baseline visit recorded participants' alcohol consumption 90 days prior to their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome reports the change in the mean drinks between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties. |
Countries
United States
Participant flow
Recruitment details
Recruitment was done from 03/03/2015 to 09/18/2018; however the last participant was recruited on 08/30/2018 because the rest of the interested individuals were not eligible. Participants were recruited primarily through letters that were sent to those whose medical records indicated they likely had an active Alcohol Use Disorder (AUD) and had not been prescribed the study medications. Other recruitment methods: flyers, VA TV monitors, and advertising in the local media.
Pre-assignment details
Interested individuals called study staff and were screened for eligibility. Out of 200 phone screens, 97 individuals were eligible and invited to the screening visit. Of these, 21 did not show or were lost to follow up, 7 canceled their visit, and 8 declined the visit. Out of 61 individuals who came to screening, 31 were eligible and randomized.
Participants by arm
| Arm | Count |
|---|---|
| Praz/Nal Prazosin and Naltrexone.
Prazosin will be taken following this titration schedule:
Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM
Naltrexone will be taken from day 1 to day 42 at 9 PM. Dose: 50 mg.
Prazosin: Prazosin Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM
Naltrexone: Naltrexone Dosing Days 1-42: 50mg @ 9PM | 7 |
| Praz/Pl Prazosin and Placebo (Naltrexone)
Prazosin will be taken following this titration schedule:
Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM
Naltrexone Placebo will be taken from day 1 to day 42 at 9 PM. Dose: 50 mg.
Prazosin: Prazosin Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM
Placebo (Naltrexone): Placebo Dosing Days 1-42: 50mg @ 9PM | 7 |
| Nal/Pl Naltrexone and Placebo (Prazosin)
Prazosin Placebo will be taken following this titration schedule:
Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM
Naltrexone will be taken from day 1 to day 42 at 9 PM. Dose: 50 mg.
Naltrexone: Naltrexone Dosing Days 1-42: 50mg @ 9PM
Placebo (Prazosin): Placebo Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM | 7 |
| Pl/Pl Placebo (Prazosin) and Placebo (Naltrexone)
Prazosin Placebo will be taken following this titration schedule:
Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM
Naltrexone Placebo will be taken from day 1 to day 42 at 9 PM. Dose: 50 mg.
Placebo (Prazosin): Placebo Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM
Placebo (Naltrexone): Placebo Dosing Days 1-42: 50mg @ 9PM | 8 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Praz/Nal | Praz/Pl | Nal/Pl | Pl/Pl | Total |
|---|---|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 12.37 | 54.86 years STANDARD_DEVIATION 9.08 | 54.43 years STANDARD_DEVIATION 6.19 | 52.38 years STANDARD_DEVIATION 10.72 | 53.14 years STANDARD_DEVIATION 9.48 |
| Alcohol craving | 18.50 scores on scale STANDARD_DEVIATION 3.89 | 20.29 scores on scale STANDARD_DEVIATION 6.68 | 16.71 scores on scale STANDARD_DEVIATION 5.59 | 16.86 scores on scale STANDARD_DEVIATION 5.76 | 18.10 scores on scale STANDARD_DEVIATION 5.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 7 Participants | 7 Participants | 5 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Mean drinks per day of drinking | 8.17 drinks STANDARD_DEVIATION 5.4 | 11.88 drinks STANDARD_DEVIATION 7.55 | 8.44 drinks STANDARD_DEVIATION 3.97 | 13.88 drinks STANDARD_DEVIATION 9.55 | 10.70 drinks STANDARD_DEVIATION 7.12 |
| Percent drinking days (PDD) | 73.10 percentage of drinking days STANDARD_DEVIATION 28.1 | 87.93 percentage of drinking days STANDARD_DEVIATION 19.87 | 64.44 percentage of drinking days STANDARD_DEVIATION 26.04 | 75.83 percentage of drinking days STANDARD_DEVIATION 21 | 75.34 percentage of drinking days STANDARD_DEVIATION 24.08 |
| Percent heavy drinking days (PHDD) | 54.99 percentage of heavy drinking days STANDARD_DEVIATION 37.18 | 77.77 percentage of heavy drinking days STANDARD_DEVIATION 28.63 | 47.62 percentage of heavy drinking days STANDARD_DEVIATION 34.51 | 66.25 percentage of heavy drinking days STANDARD_DEVIATION 33.6 | 61.81 percentage of heavy drinking days STANDARD_DEVIATION 33.77 |
| Race/Ethnicity, Customized Asian/Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Multiracial | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native American/American Indian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Prefer not to answer | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 6 Participants | 5 Participants | 4 Participants | 4 Participants | 19 Participants |
| Region of Enrollment United States | 7 participants | 7 participants | 7 participants | 8 participants | 29 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 7 Participants | 7 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 9 |
| other Total, other adverse events | 5 / 8 | 3 / 7 | 3 / 7 | 3 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 9 |
Outcome results
Primary
Change in Alcohol Craving (Visit 8 PACS - Visit 2 PACS)
Alcohol craving was assessed in visit 2 (baseline) and the last visit (visit 8) using the Pennsylvania Alcohol Craving Scale (PACS). The PACS had 5 questions, where each question had six options presented in Likert Scales from 0 to 6, with 0 being the least and 6 being the highest possible option, thus the possible minimum and maximum values are 0 and 30, respectively. Higher scores mean higher craving. This outcome measures the change in PACS scores between visits 2 and 8 (visit 8 PACS score - visit 2 PACS score). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Time frame: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.
Population: Only participants who completed the study or had an intention to treat (ITT) were included in analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Praz/Nal | Change in Alcohol Craving (Visit 8 PACS - Visit 2 PACS) | -10.5 score on a scale | Standard Error 2.4 |
| Praz/Pl | Change in Alcohol Craving (Visit 8 PACS - Visit 2 PACS) | -4.6 score on a scale | Standard Error 2.4 |
| Nal/Pl | Change in Alcohol Craving (Visit 8 PACS - Visit 2 PACS) | -4.3 score on a scale | Standard Error 2.4 |
| Pl/Pl | Change in Alcohol Craving (Visit 8 PACS - Visit 2 PACS) | -3.5 score on a scale | Standard Error 2.4 |
Primary
Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD)
PDD was calculated based on self-reported drinking history collected via Form-90. Drinking days were defined as days when participants consumed alcohol. Form-90 was completed by participants in visit 2 (baseline) and visit 8 (last visit). Form-90 collected in the baseline visit recorded participants' alcohol consumption from 90 days prior to their baseline visit until the day before their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome measures changes in PDD between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Time frame: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.
Population: Only participants who completed the study or had an intention to treat (ITT) were included in analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Praz/Nal | Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD) | -37 percentage of drinking days | Standard Error 10 |
| Praz/Pl | Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD) | -9 percentage of drinking days | Standard Error 10 |
| Nal/Pl | Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD) | -14 percentage of drinking days | Standard Error 10 |
| Pl/Pl | Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD) | -15 percentage of drinking days | Standard Error 9 |
Primary
Change in Percent Heavy Drinking Days (PHDD) (Visit 8 PHDD - Visit 2 PHDD)
PHDD was calculated based on self-reported drinking history collected via Form-90. Heavy drinking days were defined as days when participants consumed 4 or more drinks for females and 5 or more drinks for males. Form-90 was completed by participants in the baseline and last visit. Form-90 collected in the baseline visit recorded participants' alcohol consumption 90 days prior to their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome measures changes in PHDD between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Time frame: Visit 2 (baseline) and Visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.
Population: Only participants who completed the study or had an intention to treat (ITT) were included in analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Praz/Nal | Change in Percent Heavy Drinking Days (PHDD) (Visit 8 PHDD - Visit 2 PHDD) | -38 percentage of heavy drinking days | Standard Error 17 |
| Praz/Pl | Change in Percent Heavy Drinking Days (PHDD) (Visit 8 PHDD - Visit 2 PHDD) | -8 percentage of heavy drinking days | Standard Error 17 |
| Nal/Pl | Change in Percent Heavy Drinking Days (PHDD) (Visit 8 PHDD - Visit 2 PHDD) | -7 percentage of heavy drinking days | Standard Error 17 |
| Pl/Pl | Change in Percent Heavy Drinking Days (PHDD) (Visit 8 PHDD - Visit 2 PHDD) | -13 percentage of heavy drinking days | Standard Error 16 |
Secondary
Change in Mean Drinks Per Day of Drinking (Visit 8 - Visit 2)
Average drinks per day of drinking was calculated based on self-reported drinking history collected via Form-90. Drinking days were defined as days when participants consumed alcohol. Form-90 was completed by participants in visit 2 (baseline) and visit 8 (last visit). Form-90 collected in the baseline visit recorded participants' alcohol consumption 90 days prior to their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome reports the change in the mean drinks between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Time frame: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.
Population: Only participants who completed the study or had an intention to treat (ITT) were included in analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Praz/Nal | Change in Mean Drinks Per Day of Drinking (Visit 8 - Visit 2) | -5.1 drinks | Standard Error 1.7 |
| Praz/Pl | Change in Mean Drinks Per Day of Drinking (Visit 8 - Visit 2) | -2.2 drinks | Standard Error 1.7 |
| Nal/Pl | Change in Mean Drinks Per Day of Drinking (Visit 8 - Visit 2) | -5.0 drinks | Standard Error 1.7 |
| Pl/Pl | Change in Mean Drinks Per Day of Drinking (Visit 8 - Visit 2) | -3.7 drinks | Standard Error 1.6 |