Alcohol Use Disorder
Conditions
Keywords
ivermectin, alcoholism, alcohol use disorder, treatment
Brief summary
Current pharmacotherapies for alcohol use disorders (AUDs) have limited efficacy. Thus, the development of effective treatments for AUDs represents an important public health objective. Repositioning, i.e. using existing approved drugs for other indications, represents a fast and economically feasible approach for drug development. Ivermectin (IVM) is an FDA-approved antiparasitic medication that can significantly reduce alcohol intake in mice, suggesting that it may be useful in the treatment of AUDs in humans. The goal of this project is to provide key clinical evidence that IVM can be repositioned as a novel therapeutic agent to treat AUDs.
Detailed description
Current pharmacotherapies for alcohol use disorders (AUDs) have limited efficacy. Thus, the development of effective treatments for AUDs represents an important public health objective. Repositioning, i.e. using existing approved drugs for other indications, represents a fast and economically feasible approach for drug development. Ivermectin (IVM) is an FDA-approved antiparasitic medication that can significantly reduce alcohol intake in mice, suggesting that it may be useful in the treatment of AUDs in humans. The goal of this project is to provide key clinical evidence that IVM can be repositioned as a novel therapeutic agent to treat AUDs. We will enroll 10 alcohol dependent individuals in a placebo-controlled randomized pilot safety trial of IVM (30 mg orally once) over a 2-day (1-night) inpatient stay at the UCLA CTRC and employ a well-characterized battery of behavioral paradigms (i.e., alcohol administration and cue exposure). The goals of the study are to test: (a) the safety of combining IVM, at a dose currently shown to be safe in humans (30 mg), with moderate doses of alcohol (0.08 g/dl); and (b) whether IVM reduces the reinforcing effects of alcohol during alcohol administration and whether it reduces alcohol craving during cue exposure, as compared to placebo.
Interventions
DRUGIvermectin
Ivermectin is a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum antiparasitic avermectin.
DRUGPlacebo
Matched placebo
DRUGAlcohol
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* age between 21 and 65; * meet current DSM-V diagnostic criteria for an alcohol use disorder
Exclusion criteria
* current treatment for alcohol problems, a history of treatment in the 30 days before enrollment or current treatment seeking; * a current (last 12 months) DSM-V diagnosis of dependence on any psychoactive substances other than alcohol and nicotine; * a lifetime DSM-IV diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder; * positive urine screen for narcotics, amphetamines, or sedative hypnotics; * serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-R); * pregnancy, nursing, or refusal to use reliable method of birth control (if female); * a medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes); * AST, ALT, or GGT ≥ 3 times upper normal limit; * currently on prescription medication that contraindicates use of IVN; * any other circumstances that, in the opinion of the investigators, compromises participant safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Effects | During alcohol infusion at BrAC = 0.00, 0.04, 0.08 g/dl | Adverse effects will be monitored to determine the safe of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl) using the Systematic Assessment for Treatment Emergent Effects (SAFTEE). The SAFTEE is a 24-item checklist in which the participant can identify whether a symptom is present (yes/no), its severity (mild, moderate, severe) and whether it was caused by the medication (yes/no). Data below represents a count of individual adverse effects reported on the SAFTEE during the alcohol infusion. |
| Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. | Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question Would you like more of the drug right now? was rated on an 11 point scale from 0 to 10 (higher values represent more effects). |
| Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. | Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question Are you high? was rated on an 11 point scale from 0 to 10 (higher values represent more effects). |
| Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. | Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Stimulant Subscale ranges from 0 to 70. Mean scores across all subjects are reported below. |
| Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. | Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Sedative Subscale ranges from 0 to 70. Mean scores across subjects are reported below. |
| Cue-induced Craving Using the Alcohol Urge Questionnaire (AUQ) | 6 hours post-medication administration | Cue-induced craving will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (0 = strongly disagree, 6 = strongly agree). Item scores were averaged and the total score also ranges from 0-6. |
| Heart Rate | Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl | Heart rate (measured in beats per minute; BPM) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). During the infusion, the times for collecting HR will vary based on how long it takes participants to reach the targeted BrACs. |
| Systolic Blood Pressure | Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl | Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs. |
| Diastolic Blood Pressure | Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl | Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs. |
| Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. | Subjective effects of alcohol will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (1 = strongly disagree, 7 = strongly agree). |
| Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. | Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question Do you feel any drug effects? was rated on an 11 point scale from 0 to 10 (higher values represent more effects). |
| Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. | Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question Do you like the effects you are feeling right now? was rated on an 11 point scale from 0 to 10 (higher values represent more effects). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ivermectin Pharmacokinetics: Time to Cmax (Tmax) | Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 | This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Time to Cmax (Tmax), measured in hours, provided below. |
| Ivermectin Pharmacokinetics: Area Under the Time-concentration Curve (AUC) | Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 | This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Area under the time-concentration curve (AUC) from 0 to 48 hours after IVM administration, provided below. |
| Ivermectin Pharmacokinetics: Half-life (T1/2) | Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 | This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Half-life of ivermectin (T1/2), measured in hours, provided below. |
| Stress-induced Alcohol Craving | pre-post exposure to an imaginal stress script | Alcohol Urge Questionnaire (AUQ) |
| Ivermectin Pharmacokinetics: Peak Concentration (Cmax) | Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 | This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Maximum plasma concentration (Cmax), measured in ng/mL, provided below. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IVM 30mg; Placebo Ivermectin (IVM): Single dose (30 mg) of a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin.
Placebo: Single dose sugar pill matched to active medication. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | IVM 30mg; Placebo |
|---|---|
| Age, Continuous | 38.82 years STANDARD_DEVIATION 11.39 |
| Meets criteria for DSM-V AD | 11 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Adverse Effects
Adverse effects will be monitored to determine the safe of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl) using the Systematic Assessment for Treatment Emergent Effects (SAFTEE). The SAFTEE is a 24-item checklist in which the participant can identify whether a symptom is present (yes/no), its severity (mild, moderate, severe) and whether it was caused by the medication (yes/no). Data below represents a count of individual adverse effects reported on the SAFTEE during the alcohol infusion.
Time frame: During alcohol infusion at BrAC = 0.00, 0.04, 0.08 g/dl
Population: All randomized subjects included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Adverse Effects | Drowsiness | 2 adverse effect count |
| Placebo | Adverse Effects | Decrease in appetite | 0 adverse effect count |
| Placebo | Adverse Effects | Yellow eyes | 0 adverse effect count |
| Placebo | Adverse Effects | Abdominal pain/cramps | 0 adverse effect count |
| Placebo | Adverse Effects | Fatigue | 1 adverse effect count |
| Placebo | Adverse Effects | Depression | 0 adverse effect count |
| Placebo | Adverse Effects | Difficulty sleeping | 0 adverse effect count |
| Placebo | Adverse Effects | Blurred vision | 1 adverse effect count |
| Placebo | Adverse Effects | Increase in appetite | 0 adverse effect count |
| Placebo | Adverse Effects | Difficulty in staying awake | 3 adverse effect count |
| Placebo | Adverse Effects | Nervousness | 1 adverse effect count |
| Placebo | Adverse Effects | Nausea or vomiting | 0 adverse effect count |
| Placebo | Adverse Effects | Anxiety | 0 adverse effect count |
| Placebo | Adverse Effects | Irritability or anger | 1 adverse effect count |
| Placebo | Adverse Effects | Fever or chills | 0 adverse effect count |
| Placebo | Adverse Effects | Increased desire for sex | 1 adverse effect count |
| Placebo | Adverse Effects | Night sweats | 0 adverse effect count |
| Placebo | Adverse Effects | Decreased desire for sex | 0 adverse effect count |
| Placebo | Adverse Effects | Sexual problems | 0 adverse effect count |
| Placebo | Adverse Effects | Dizziness | 0 adverse effect count |
| Placebo | Adverse Effects | Joint or muscle pain | 0 adverse effect count |
| Placebo | Adverse Effects | Mental confusion | 0 adverse effect count |
| Placebo | Adverse Effects | Ringing in the ears | 0 adverse effect count |
| Placebo | Adverse Effects | Headache | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Fatigue | 2 adverse effect count |
| IVM 30mg | Adverse Effects | Abdominal pain/cramps | 1 adverse effect count |
| IVM 30mg | Adverse Effects | Yellow eyes | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Nausea or vomiting | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Increased desire for sex | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Decrease in appetite | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Blurred vision | 1 adverse effect count |
| IVM 30mg | Adverse Effects | Drowsiness | 4 adverse effect count |
| IVM 30mg | Adverse Effects | Decreased desire for sex | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Joint or muscle pain | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Dizziness | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Sexual problems | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Fever or chills | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Irritability or anger | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Nervousness | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Ringing in the ears | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Depression | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Difficulty in staying awake | 3 adverse effect count |
| IVM 30mg | Adverse Effects | Increase in appetite | 1 adverse effect count |
| IVM 30mg | Adverse Effects | Headache | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Night sweats | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Mental confusion | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Anxiety | 0 adverse effect count |
| IVM 30mg | Adverse Effects | Difficulty sleeping | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Drowsiness | 2 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Irritability or anger | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Increase in appetite | 3 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Fever or chills | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Nervousness | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Difficulty in staying awake | 4 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Decreased desire for sex | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Decrease in appetite | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Ringing in the ears | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Fatigue | 2 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Abdominal pain/cramps | 1 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Dizziness | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Joint or muscle pain | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Nausea or vomiting | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Increased desire for sex | 1 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Anxiety | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Depression | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Headache | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Yellow eyes | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Difficulty sleeping | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Mental confusion | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Blurred vision | 1 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Night sweats | 0 adverse effect count |
| Placebo (BrAC = 0.08) | Adverse Effects | Sexual problems | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Dizziness | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Ringing in the ears | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Night sweats | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Difficulty sleeping | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Anxiety | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Depression | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Decrease in appetite | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Difficulty in staying awake | 3 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Sexual problems | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Increase in appetite | 1 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Abdominal pain/cramps | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Fever or chills | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Decreased desire for sex | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Mental confusion | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Nausea or vomiting | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Irritability or anger | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Increased desire for sex | 1 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Joint or muscle pain | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Fatigue | 1 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Yellow eyes | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Nervousness | 1 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Blurred vision | 0 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Drowsiness | 2 adverse effect count |
| IVM 30mg (BrAC = 0.00) | Adverse Effects | Headache | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Decreased desire for sex | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Ringing in the ears | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Dizziness | 1 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Depression | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Difficulty in staying awake | 2 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Fatigue | 1 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Joint or muscle pain | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Yellow eyes | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Sexual problems | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Fever or chills | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Decrease in appetite | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Night sweats | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Anxiety | 1 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Increase in appetite | 2 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Abdominal pain/cramps | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Blurred vision | 1 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Irritability or anger | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Difficulty sleeping | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Nervousness | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Headache | 1 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Increased desire for sex | 2 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Mental confusion | 0 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Drowsiness | 4 adverse effect count |
| IVM 30mg (BrAC = 0.04) | Adverse Effects | Nausea or vomiting | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Ringing in the ears | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Nervousness | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Dizziness | 2 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Fever or chills | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Increased desire for sex | 1 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Decreased desire for sex | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Abdominal pain/cramps | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Nausea or vomiting | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Anxiety | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Irritability or anger | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Yellow eyes | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Joint or muscle pain | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Fatigue | 2 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Sexual problems | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Drowsiness | 5 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Headache | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Difficulty sleeping | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Night sweats | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Decrease in appetite | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Depression | 0 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Difficulty in staying awake | 2 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Increase in appetite | 4 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Blurred vision | 1 adverse effect count |
| IVM 30mg (BrAC = 0.08) | Adverse Effects | Mental confusion | 0 adverse effect count |
Primary
Cue-induced Craving Using the Alcohol Urge Questionnaire (AUQ)
Cue-induced craving will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (0 = strongly disagree, 6 = strongly agree). Item scores were averaged and the total score also ranges from 0-6.
Time frame: 6 hours post-medication administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cue-induced Craving Using the Alcohol Urge Questionnaire (AUQ) | 3.59 scores on a scale | Standard Deviation 1.69 |
| IVM 30mg | Cue-induced Craving Using the Alcohol Urge Questionnaire (AUQ) | 4.07 scores on a scale | Standard Deviation 1.34 |
p-value: 0.99ANOVA
Primary
Diastolic Blood Pressure
Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs.
Time frame: Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Diastolic Blood Pressure | 10 hours post-med | 75.30 mmHg | Standard Deviation 11.88 |
| Placebo | Diastolic Blood Pressure | BrAC = 0.02 | 77.91 mmHg | Standard Deviation 10.01 |
| Placebo | Diastolic Blood Pressure | 0 hours post-med | 79.64 mmHg | Standard Deviation 10.23 |
| Placebo | Diastolic Blood Pressure | 0.5 hours post-med | 77.45 mmHg | Standard Deviation 11.44 |
| Placebo | Diastolic Blood Pressure | 2 hours post-med | 79.91 mmHg | Standard Deviation 8.8 |
| Placebo | Diastolic Blood Pressure | 12 hours post-med | 73.64 mmHg | Standard Deviation 9.84 |
| Placebo | Diastolic Blood Pressure | 6 hours post-med | 75.36 mmHg | Standard Deviation 14.49 |
| Placebo | Diastolic Blood Pressure | 1 hour post-med | 78.82 mmHg | Standard Deviation 10.3 |
| Placebo | Diastolic Blood Pressure | BrAC = 0 | 78.18 mmHg | Standard Deviation 11.57 |
| Placebo | Diastolic Blood Pressure | 16 hours post-med | 72.82 mmHg | Standard Deviation 12.69 |
| Placebo | Diastolic Blood Pressure | 8 hours post-med | 72.55 mmHg | Standard Deviation 10.05 |
| Placebo | Diastolic Blood Pressure | BrAC = 0.04 | 77.55 mmHg | Standard Deviation 10.71 |
| Placebo | Diastolic Blood Pressure | 24 hours post-med | 76.09 mmHg | Standard Deviation 12.39 |
| Placebo | Diastolic Blood Pressure | BrAC = 0.06 | 75.27 mmHg | Standard Deviation 9.31 |
| Placebo | Diastolic Blood Pressure | 4 hours post-med | 74.55 mmHg | Standard Deviation 10.82 |
| Placebo | Diastolic Blood Pressure | BrAC = 0.08 | 71.91 mmHg | Standard Deviation 10.9 |
| Placebo | Diastolic Blood Pressure | 48 hours post-med | 80.55 mmHg | Standard Deviation 10.96 |
| IVM 30mg | Diastolic Blood Pressure | BrAC = 0.08 | 72.73 mmHg | Standard Deviation 10.75 |
| IVM 30mg | Diastolic Blood Pressure | 0.5 hours post-med | 75.18 mmHg | Standard Deviation 11.12 |
| IVM 30mg | Diastolic Blood Pressure | 1 hour post-med | 74.91 mmHg | Standard Deviation 10.43 |
| IVM 30mg | Diastolic Blood Pressure | 2 hours post-med | 76.64 mmHg | Standard Deviation 12.14 |
| IVM 30mg | Diastolic Blood Pressure | 6 hours post-med | 74.55 mmHg | Standard Deviation 11.22 |
| IVM 30mg | Diastolic Blood Pressure | 8 hours post-med | 69.45 mmHg | Standard Deviation 10.46 |
| IVM 30mg | Diastolic Blood Pressure | 12 hours post-med | 77.27 mmHg | Standard Deviation 6.44 |
| IVM 30mg | Diastolic Blood Pressure | 16 hours post-med | 73.18 mmHg | Standard Deviation 8.81 |
| IVM 30mg | Diastolic Blood Pressure | 24 hours post-med | 78.09 mmHg | Standard Deviation 10.23 |
| IVM 30mg | Diastolic Blood Pressure | 48 hours post-med | 81.55 mmHg | Standard Deviation 10.49 |
| IVM 30mg | Diastolic Blood Pressure | 4 hours post-med | 72.18 mmHg | Standard Deviation 10.91 |
| IVM 30mg | Diastolic Blood Pressure | 10 hours post-med | 73.82 mmHg | Standard Deviation 12.6 |
| IVM 30mg | Diastolic Blood Pressure | BrAC = 0 | 74.36 mmHg | Standard Deviation 12.49 |
| IVM 30mg | Diastolic Blood Pressure | BrAC = 0.02 | 73.73 mmHg | Standard Deviation 10.96 |
| IVM 30mg | Diastolic Blood Pressure | BrAC = 0.04 | 72.91 mmHg | Standard Deviation 11.89 |
| IVM 30mg | Diastolic Blood Pressure | BrAC = 0.06 | 74.00 mmHg | Standard Deviation 12.13 |
| IVM 30mg | Diastolic Blood Pressure | 0 hours post-med | 75.55 mmHg | Standard Deviation 13.2 |
p-value: 0.1597ANOVA
Primary
Heart Rate
Heart rate (measured in beats per minute; BPM) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). During the infusion, the times for collecting HR will vary based on how long it takes participants to reach the targeted BrACs.
Time frame: Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Heart Rate | BrAC = 0.08 | 66.36 BPM | Standard Deviation 12.37 |
| Placebo | Heart Rate | 0 hours post-med | 64.57 BPM | Standard Deviation 9.74 |
| Placebo | Heart Rate | 24 hours post-med | 62.55 BPM | Standard Deviation 11.09 |
| Placebo | Heart Rate | 0.5 hours post-med | 66.82 BPM | Standard Deviation 10.91 |
| Placebo | Heart Rate | BrAC = 0 | 63.09 BPM | Standard Deviation 12.69 |
| Placebo | Heart Rate | 1 hour post-med | 66.09 BPM | Standard Deviation 12.01 |
| Placebo | Heart Rate | 8 hours post-med | 66.36 BPM | Standard Deviation 13.44 |
| Placebo | Heart Rate | 2 hours post-med | 65.18 BPM | Standard Deviation 13.88 |
| Placebo | Heart Rate | BrAC = 0.02 | 67.27 BPM | Standard Deviation 14 |
| Placebo | Heart Rate | 4 hours post-med | 66.73 BPM | Standard Deviation 10.6 |
| Placebo | Heart Rate | 12 hours post-med | 72.45 BPM | Standard Deviation 13.41 |
| Placebo | Heart Rate | 6 hours post-med | 63.27 BPM | Standard Deviation 12.66 |
| Placebo | Heart Rate | BrAC = 0.04 | 66.91 BPM | Standard Deviation 10.89 |
| Placebo | Heart Rate | 16 hours post-med | 61.18 BPM | Standard Deviation 12.08 |
| Placebo | Heart Rate | BrAC = 0.06 | 66.64 BPM | Standard Deviation 12.83 |
| Placebo | Heart Rate | 48 hours post-med | 69.18 BPM | Standard Deviation 10.15 |
| Placebo | Heart Rate | 10 hours post-med | 64.70 BPM | Standard Deviation 14.33 |
| IVM 30mg | Heart Rate | 48 hours post-med | 69.45 BPM | Standard Deviation 12.49 |
| IVM 30mg | Heart Rate | 8 hours post-med | 62.18 BPM | Standard Deviation 11.76 |
| IVM 30mg | Heart Rate | 10 hours post-med | 62.64 BPM | Standard Deviation 10.19 |
| IVM 30mg | Heart Rate | 16 hours post-med | 58.09 BPM | Standard Deviation 10.97 |
| IVM 30mg | Heart Rate | BrAC = 0 | 61.00 BPM | Standard Deviation 11.8 |
| IVM 30mg | Heart Rate | BrAC = 0.02 | 63.36 BPM | Standard Deviation 9 |
| IVM 30mg | Heart Rate | BrAC = 0.04 | 61.82 BPM | Standard Deviation 9.16 |
| IVM 30mg | Heart Rate | BrAC = 0.06 | 63.09 BPM | Standard Deviation 9.82 |
| IVM 30mg | Heart Rate | 0 hours post-med | 68.36 BPM | Standard Deviation 20.47 |
| IVM 30mg | Heart Rate | 0.5 hours post-med | 62.82 BPM | Standard Deviation 11.46 |
| IVM 30mg | Heart Rate | 1 hour post-med | 64.27 BPM | Standard Deviation 11.6 |
| IVM 30mg | Heart Rate | 2 hours post-med | 61.18 BPM | Standard Deviation 11.03 |
| IVM 30mg | Heart Rate | 4 hours post-med | 61.55 BPM | Standard Deviation 12.36 |
| IVM 30mg | Heart Rate | 6 hours post-med | 59.73 BPM | Standard Deviation 12.62 |
| IVM 30mg | Heart Rate | 12 hours post-med | 73.64 BPM | Standard Deviation 9.31 |
| IVM 30mg | Heart Rate | 24 hours post-med | 64.64 BPM | Standard Deviation 10.58 |
| IVM 30mg | Heart Rate | BrAC = 0.08 | 61.27 BPM | Standard Deviation 8.21 |
p-value: 0.0563ANOVA
Primary
Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ)
Subjective effects of alcohol will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (1 = strongly disagree, 7 = strongly agree).
Time frame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.00 | 2.58 scores on a scale | Standard Deviation 1.74 |
| Placebo | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.04 | 3.02 scores on a scale | Standard Deviation 1.64 |
| Placebo | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.06 | 2.73 scores on a scale | Standard Deviation 2 |
| Placebo | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.08 | 2.83 scores on a scale | Standard Deviation 1.79 |
| Placebo | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.02 | 3.14 scores on a scale | Standard Deviation 1.64 |
| IVM 30mg | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.08 | 2.91 scores on a scale | Standard Deviation 1.87 |
| IVM 30mg | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.00 | 2.90 scores on a scale | Standard Deviation 2.04 |
| IVM 30mg | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.02 | 3.27 scores on a scale | Standard Deviation 1.65 |
| IVM 30mg | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.06 | 2.60 scores on a scale | Standard Deviation 1.6 |
| IVM 30mg | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) | BrAC = 0.04 | 3.19 scores on a scale | Standard Deviation 1.6 |
p-value: 0.7617ANOVA
Primary
Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale
Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Sedative Subscale ranges from 0 to 70. Mean scores across subjects are reported below.
Time frame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.00 | 14.18 scores on a scale | Standard Deviation 14.67 |
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.02 | 11.00 scores on a scale | Standard Deviation 13.1 |
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.04 | 10.91 scores on a scale | Standard Deviation 14.72 |
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.06 | 15.27 scores on a scale | Standard Deviation 17.41 |
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.08 | 15.27 scores on a scale | Standard Deviation 18.93 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.04 | 16.00 scores on a scale | Standard Deviation 15.75 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.00 | 10.64 scores on a scale | Standard Deviation 9.97 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.06 | 16.73 scores on a scale | Standard Deviation 19.22 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.02 | 13.09 scores on a scale | Standard Deviation 14.8 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale | BrAC = 0.08 | 16.64 scores on a scale | Standard Deviation 17.32 |
p-value: 0.09ANOVA
Primary
Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale
Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Stimulant Subscale ranges from 0 to 70. Mean scores across all subjects are reported below.
Time frame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.00 | 18.09 scores on a scale | Standard Deviation 13.37 |
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.02 | 20.00 scores on a scale | Standard Deviation 11.91 |
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.04 | 21.73 scores on a scale | Standard Deviation 15.04 |
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.06 | 25.91 scores on a scale | Standard Deviation 19.03 |
| Placebo | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.08 | 26.18 scores on a scale | Standard Deviation 20.17 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.06 | 22.64 scores on a scale | Standard Deviation 15.74 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.00 | 17.36 scores on a scale | Standard Deviation 12.99 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.08 | 20.91 scores on a scale | Standard Deviation 15 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.02 | 23.73 scores on a scale | Standard Deviation 14.29 |
| IVM 30mg | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale | BrAC = 0.04 | 20.09 scores on a scale | Standard Deviation 13.32 |
p-value: 0.21ANOVA
Primary
Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale
Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question Do you feel any drug effects? was rated on an 11 point scale from 0 to 10 (higher values represent more effects).
Time frame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.04 | 3.82 scores on a scale | Standard Deviation 2.75 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.06 | 4.45 scores on a scale | Standard Deviation 3.48 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.08 | 5.27 scores on a scale | Standard Deviation 3.29 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.00 | 1.36 scores on a scale | Standard Deviation 2.66 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.02 | 2.73 scores on a scale | Standard Deviation 2.45 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.02 | 3.45 scores on a scale | Standard Deviation 2.21 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.04 | 4.82 scores on a scale | Standard Deviation 3.03 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.00 | 0.91 scores on a scale | Standard Deviation 1.3 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.06 | 5.36 scores on a scale | Standard Deviation 3.33 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Feel Subscale | BrAC = 0.08 | 6.36 scores on a scale | Standard Deviation 2.8 |
p-value: 0.93ANOVA
Primary
Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale
Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question Are you high? was rated on an 11 point scale from 0 to 10 (higher values represent more effects).
Time frame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.00 | 0.91 scores on a scale | Standard Deviation 1.7 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.06 | 4.91 scores on a scale | Standard Deviation 3.56 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.02 | 2.64 scores on a scale | Standard Deviation 2.29 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.04 | 4.00 scores on a scale | Standard Deviation 2.93 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.08 | 5.09 scores on a scale | Standard Deviation 3.62 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.08 | 6.00 scores on a scale | Standard Deviation 2.79 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.00 | 0.09 scores on a scale | Standard Deviation 0.3 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.04 | 5.36 scores on a scale | Standard Deviation 2.66 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.02 | 3.27 scores on a scale | Standard Deviation 2.01 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - High Subscale | BrAC = 0.06 | 5.73 scores on a scale | Standard Deviation 2.57 |
p-value: 0.06ANOVA
Primary
Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale
Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question Do you like the effects you are feeling right now? was rated on an 11 point scale from 0 to 10 (higher values represent more effects).
Time frame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.06 | 6.64 scores on a scale | Standard Deviation 2.98 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.02 | 5.36 scores on a scale | Standard Deviation 1.63 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.08 | 6.45 scores on a scale | Standard Deviation 3.33 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.04 | 6.18 scores on a scale | Standard Deviation 2.52 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.00 | 4.09 scores on a scale | Standard Deviation 1.7 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.04 | 5.55 scores on a scale | Standard Deviation 2.95 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.00 | 4.09 scores on a scale | Standard Deviation 2.02 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.06 | 6.36 scores on a scale | Standard Deviation 3.44 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.08 | 6.27 scores on a scale | Standard Deviation 3.5 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - Like Subscale | BrAC = 0.02 | 5.36 scores on a scale | Standard Deviation 3.2 |
p-value: 0.95ANOVA
Primary
Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale
Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question Would you like more of the drug right now? was rated on an 11 point scale from 0 to 10 (higher values represent more effects).
Time frame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.04 | 5.45 scores on a scale | Standard Deviation 3.96 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.08 | 5.27 scores on a scale | Standard Deviation 4.25 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.06 | 5.00 scores on a scale | Standard Deviation 3.92 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.02 | 4.91 scores on a scale | Standard Deviation 4.09 |
| Placebo | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.00 | 1.64 scores on a scale | Standard Deviation 2.25 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.02 | 6.27 scores on a scale | Standard Deviation 4.52 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.00 | 3.18 scores on a scale | Standard Deviation 4 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.04 | 6.00 scores on a scale | Standard Deviation 3.95 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.06 | 5.64 scores on a scale | Standard Deviation 4.03 |
| IVM 30mg | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - More Subscale | BrAC = 0.08 | 5.55 scores on a scale | Standard Deviation 4.78 |
p-value: 0.43ANOVA
Primary
Systolic Blood Pressure
Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs.
Time frame: Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl
Population: All randomized subjects included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Systolic Blood Pressure | 1 hour post-med | 120.64 mmHg | Standard Deviation 11.44 |
| Placebo | Systolic Blood Pressure | 10 hours post-med | 116.70 mmHg | Standard Deviation 13.49 |
| Placebo | Systolic Blood Pressure | BrAC = 0 | 120.27 mmHg | Standard Deviation 15.07 |
| Placebo | Systolic Blood Pressure | 12 hours post-med | 116.09 mmHg | Standard Deviation 9.17 |
| Placebo | Systolic Blood Pressure | 16 hours post-med | 115.64 mmHg | Standard Deviation 17.19 |
| Placebo | Systolic Blood Pressure | 2 hours post-med | 121.27 mmHg | Standard Deviation 10.59 |
| Placebo | Systolic Blood Pressure | 24 hours post-med | 122 mmHg | Standard Deviation 11.61 |
| Placebo | Systolic Blood Pressure | 8 hours post-med | 115.18 mmHg | Standard Deviation 13.5 |
| Placebo | Systolic Blood Pressure | 48 hours post-med | 122.72 mmHg | Standard Deviation 8.67 |
| Placebo | Systolic Blood Pressure | 4 hours post-med | 117 mmHg | Standard Deviation 12.15 |
| Placebo | Systolic Blood Pressure | BrAC = 0.02 | 118.55 mmHg | Standard Deviation 10.56 |
| Placebo | Systolic Blood Pressure | BrAC = 0.04 | 116.55 mmHg | Standard Deviation 12.36 |
| Placebo | Systolic Blood Pressure | 6 hours post-med | 117.27 mmHg | Standard Deviation 16.17 |
| Placebo | Systolic Blood Pressure | BrAC = 0.06 | 112.73 mmHg | Standard Deviation 11.4 |
| Placebo | Systolic Blood Pressure | 0.5 hours post-med | 118.64 mmHg | Standard Deviation 10.67 |
| Placebo | Systolic Blood Pressure | BrAC = 0.08 | 112.45 mmHg | Standard Deviation 12.6 |
| Placebo | Systolic Blood Pressure | 0 hours post-med | 121 mmHg | Standard Deviation 11.1 |
| IVM 30mg | Systolic Blood Pressure | BrAC = 0.08 | 108.82 mmHg | Standard Deviation 11.5 |
| IVM 30mg | Systolic Blood Pressure | 0.5 hours post-med | 117 mmHg | Standard Deviation 12.61 |
| IVM 30mg | Systolic Blood Pressure | 12 hours post-med | 119.63 mmHg | Standard Deviation 7.99 |
| IVM 30mg | Systolic Blood Pressure | BrAC = 0 | 114.36 mmHg | Standard Deviation 12.75 |
| IVM 30mg | Systolic Blood Pressure | 0 hours post-med | 111.64 mmHg | Standard Deviation 17.35 |
| IVM 30mg | Systolic Blood Pressure | 1 hour post-med | 116.27 mmHg | Standard Deviation 11.8 |
| IVM 30mg | Systolic Blood Pressure | 2 hours post-med | 118.27 mmHg | Standard Deviation 12.48 |
| IVM 30mg | Systolic Blood Pressure | 4 hours post-med | 111.91 mmHg | Standard Deviation 12.85 |
| IVM 30mg | Systolic Blood Pressure | 6 hours post-med | 119.55 mmHg | Standard Deviation 15.33 |
| IVM 30mg | Systolic Blood Pressure | 8 hours post-med | 107.27 mmHg | Standard Deviation 10.56 |
| IVM 30mg | Systolic Blood Pressure | 10 hours post-med | 114.09 mmHg | Standard Deviation 13.63 |
| IVM 30mg | Systolic Blood Pressure | 16 hours post-med | 115.45 mmHg | Standard Deviation 8.85 |
| IVM 30mg | Systolic Blood Pressure | 24 hours post-med | 122.73 mmHg | Standard Deviation 8.72 |
| IVM 30mg | Systolic Blood Pressure | 48 hours post-med | 121.09 mmHg | Standard Deviation 9.47 |
| IVM 30mg | Systolic Blood Pressure | BrAC = 0.02 | 114.18 mmHg | Standard Deviation 12.34 |
| IVM 30mg | Systolic Blood Pressure | BrAC = 0.04 | 111.27 mmHg | Standard Deviation 10.72 |
| IVM 30mg | Systolic Blood Pressure | BrAC = 0.06 | 115.18 mmHg | Standard Deviation 14.08 |
p-value: 0.0342ANOVA
Secondary
Ivermectin Pharmacokinetics: Area Under the Time-concentration Curve (AUC)
This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Area under the time-concentration curve (AUC) from 0 to 48 hours after IVM administration, provided below.
Time frame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48
Population: All randomized subjects included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ivermectin Pharmacokinetics: Area Under the Time-concentration Curve (AUC) | 5078 ng*h/mL | Standard Deviation 4258 |
Secondary
Ivermectin Pharmacokinetics: Half-life (T1/2)
This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Half-life of ivermectin (T1/2), measured in hours, provided below.
Time frame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ivermectin Pharmacokinetics: Half-life (T1/2) | 15.75 hours | Standard Deviation 6.86 |
Secondary
Ivermectin Pharmacokinetics: Peak Concentration (Cmax)
This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Maximum plasma concentration (Cmax), measured in ng/mL, provided below.
Time frame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48
Population: All randomized subjects included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ivermectin Pharmacokinetics: Peak Concentration (Cmax) | 406.03 ng/mL | Standard Deviation 398.36 |
Secondary
Ivermectin Pharmacokinetics: Time to Cmax (Tmax)
This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Time to Cmax (Tmax), measured in hours, provided below.
Time frame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48
Population: All randomized subjects included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ivermectin Pharmacokinetics: Time to Cmax (Tmax) | 9.09 hours | Standard Deviation 3.62 |
Secondary
Stress-induced Alcohol Craving
Alcohol Urge Questionnaire (AUQ)
Time frame: pre-post exposure to an imaginal stress script
Population: The stress paradigm (pre-post exposure to an imaginal stress script) was not implemented from the outset of the study due to feasibility reasons. In particular, the investigators were concerned that the timing of the stress exposure might contaminate the effects of the alcohol administration.