Aldehyde Dehydrogenase-2 (ALDH2) Deficiency
Conditions
Keywords
acetaldehyde, ethanol, ALDH2
Brief summary
This trial will evaluate if fomepizole (4-methylpyrazole) can treat symptoms associated with alcohol intolerance due to aldehyde dehydrogenase 2 (ALDH2) deficiency, an inherited metabolic disorder. These symptoms include flushing, nausea, headache, shortness of breath and dizziness, resulting from exposure to acetaldehyde, the primary metabolite of ethanol. Long-term, serious health risks have been associated with repeated exposure to acetaldehyde, a carcinogen, among ALDH2-deficient individuals.
Detailed description
Approximately 32 subjects will be enrolled in ascending dosing cohorts of 8 subjects each. Each subject will receive an oral dose of study drug (fomepizole or placebo) with concomitant ethanol with group assignment in a randomized 1:1:1:1 ratio (2 subjects each group) on Study Day 1. Each subject is their own intra-subject control with the alternative study drug (fomepizole or placebo) administered on the next day (Study Day 2). Four subjects in each cohort will receive study drug (fomepizole or placebo) administered 30 minutes prior to ethanol, 4 with study drug (fomepizole or placebo) administered 30 minutes after ethanol. The study will assess safety and tolerability of fomepizole and the PK/PD of 4-MP, ethanol and acetaldehyde in the subject population. Study with completed results acquired from Horizon in 2024.
Interventions
DRUGAntizol
DRUGPlacebo
OTHEREthanol
oral dose of ethanol (0.5 g/kg)
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent * Age 21 to 50 years * Subject of Japanese descent * History of flushing, with or without palpitations, or nausea (Alcohol Sensitivity Screening Test ≥ 3.1) following occasional or inadvertent ethanol consumption either currently or in the past * Subjects must be healthy volunteers with no other clinically relevant abnormalities as determined by medical history, blood chemistry, complete blood count (CBC), urinalysis,and 12-lead electrocardiogram (ECG) * Positive skin ethanol patch test (100 μL of 70% ethanol on a lint pad applied to skin for 7 minutes results in an area of erythema) * For Cohort 4, enrolled subjects were either homozygous or heterozygous for the ALDH2\*2 genotype as assessed by genotyping at Screening
Exclusion criteria
* Vaccination within 2 weeks of Day 1 * Current respiratory disease or a past history of chronic respiratory disease, or current smoker within last six months * Any one of the following Screening ECG findings: * QTc (Bazett) interval duration greater than 450 msec (male) or 470 msec (female), or * QRS interval greater than 120 msec, or * PR interval greater than 220 msec * History or evidence of drug or alcohol abuse or regular consumption of more than 8 units of alcohol daily (1 unit = 300 mL beer, 1 glass wine, 1 measure spirit) or those who may have difficulty abstaining from non study alcohol during the 36 hours prior to dose administration and until completion of blood sampling on Day 7 * Subjects who have donated blood totalling more than 550 mL within the 3 months prior to Day 1 * Use of any prescription medication other than oral contraceptives during the 14 days prior to Day 1, unless approved by both the Principal Investigator (PI) and the Sponsor * Inability to abstain from smoking any tobacco product from within prior to 2 hours of blood sampling to after 2 hours of blood sampling during the study period. * Use of any over-the-counter product, herbal product, diet aid, hormone supplement, etc., within 14 days prior to Day 1 unless approved by both the PI and the Sponsor * Chronic use of pain medications * Administration of an investigational agent within the last 30 days (or within a period of less than 5 times the agent's half-life, whichever is longer) prior to Day 1 * Major surgery within 60 days prior to Day 1, or any planned surgery or medical procedure during the study period (through Day 7) * Positive alcohol breath-test or Positive drug screen (e.g., opiates, barbiturates, cannabinoids, benzodiazepines, cocaine, amphetamines) during screening or at Day 0 Check-In * Known hypersensitivity reaction to Antizol® or other pyrazoles, tomato juice * Abnormal laboratory results, including: * WBC ≤3.5 × 109/L or neutrophil count ≤2.0 × 10\^9/L * Hemoglobin \<12.0 or \>16.0 gm/dL * Creatinine ≥2 mg/dL * Total bilirubin ≥2 mg/dL * Alanine aminotransferase and/or aspartate aminotransferase ≥2 times the upper limit of normal * PaO2 ≤95% on room air by pulse oximetry * Urine dipstick positive for protein, blood, ketones, glucose or leukocyte esterase * Any other clinically significant abnormal result for hematology, clinical chemistry, or urinalysis at screening or check-In * Positive serum pregnancy test for females of childbearing potential * Subject and/or partner unable or unwilling to use an effective form of barrier contraceptives during the course of the study and for 7 days after study drug administration. * Cancer (excluding adequately treated basal cell carcinoma) within the last 5 years * Significant past medical history of hepatic, renal, cardiovascular (including family history of prolonged QT syndrome), pulmonary, gastrointestinal, hematological, locomotor, immunologic, ophthalmologic, metabolic endocrine or other diseases; or any condition that in the opinion of the Investigator would complicate or compromise the study, or the well-being of the subject * Any other reason, which in the opinion of the Principal Investigator, would prevent the subject from completing or following the study schedule
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Study Day 0 through Study Visit Day 7 | AEs were collected to evaluate the safety and tolerability of oral Antizol with concomitant ethanol administration in particitpants with symptoms of acetaldehyde toxicity associated with altered ethanol metabolism. AE: any untoward medical event that occurs following the first administration of study medication until the study participant's last study visit, whether or not the event is considered drug related. SAE: an event that meets any of the following criteria: results in death; is life threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in the offspring of an exposed subject; is medically significant or an important medical event as assessed by investigator or sponsor; is, in the opinion of the investigator, an important medical event. |
Secondary
| Measure | Time frame |
|---|---|
| PK of Ethanol: AUC(0-∞) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| Pharmacokinetics (PK) of 4-MP: Maximum Plasma Concentration (Cmax) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: Dose-Normalized (DN) Cmax | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: Time to Cmax (Tmax) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: Area Under the Plasma Concentration-Time Curve (AUC), Calculated to the Last Measured Concentration (AUC[0-t]) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: DN AUC(0-t) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: AUC, From Time 0 Extrapolated to Infinite Time (AUC[0-∞]) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: DN AUC(0-∞) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: Percentage of AUC0-∞ Obtained by Extrapolation (AUC%Extrap) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: Half-Life (T1/2) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: Apparent Clearance (CL/F) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of 4-MP: Apparent Volume of Distribution During Terminal Phase (Vz/F) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: Cmax | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: DN Cmax | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: Tmax | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: DN AUC(0-t) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: DN AUC(0-∞) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: AUC%Extrap | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: T1/2 | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: CL/F | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: Vz/F | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Acetaldehyde: Cmax | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Acetaldehyde: DN Cmax | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Acetaldehyde: Tmax | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Acetaldehyde: AUC(0-t) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Acetaldehyde: DN AUC(0-t) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Acetaldehyde: AUC(0-∞) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Acetaldehyde: DN AUC(0-∞) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Acetaldehyde: AUC%Extrap | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Acetaldehyde: T1/2 | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
| PK of Ethanol: AUC(0-t) | Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment |
Countries
United States
Participant flow
Pre-assignment details
Although originally planned to receive Antizol 7.0 mg/kg, participants in Cohort 4 were dosed with study drug (Antizol or placebo) at 1.0 mg/kg,the same level dosed for the Cohort 1 participants. As a result, Cohorts 1 and 4 were combined together in the data summary and statistical analyses.
Participants by arm
| Arm | Count |
|---|---|
| Antizol 1.0 mg/kg and Placebo Participants received alternating study treatment (oral Antizol 1.0 mg/kg or placebo) on 2 sequential days (Study Day 1 and Study Day 2), administered 30 minutes prior to ethanol or 30 minutes after ethanol. | 16 |
| Antizol 3.0 mg/kg and Placebo Participants receive alternating study treatment (oral Antizol 3.0 mg/kg or placebo) on 2 sequential days (Study Day 1 and Study Day 2), administered 30 minutes prior to ethanol or 30 minutes after ethanol. | 8 |
| Antizol 5.0 mg/kg and Placebo Participants receive alternating study treatment (oral Antizol 5.0 mg/kg or placebo) on 2 sequential days (Study Day 1 and Study Day 2), administered 30 minutes prior to ethanol or 30 minutes after ethanol. | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Antizol 3.0 mg/kg and Placebo | Antizol 5.0 mg/kg and Placebo | Total | Antizol 1.0 mg/kg and Placebo |
|---|---|---|---|---|
| Age, Continuous | 29 years | 34 years | 34 years | 38 years |
| Race/Ethnicity, Customized Asian | 8 Participants | 8 Participants | 32 Participants | 16 Participants |
| Race/Ethnicity, Customized Born in Japan | 7 Participants | 8 Participants | 25 Participants | 10 Participants |
| Race/Ethnicity, Customized Japanese Ancestry | 8 Participants | 8 Participants | 32 Participants | 16 Participants |
| Race/Ethnicity, Customized Not Born in Japan | 1 Participants | 0 Participants | 7 Participants | 6 Participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 8 Participants | 8 Participants | 32 Participants | 16 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 14 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 18 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 16 | 6 / 8 | 8 / 8 | 21 / 32 | 28 / 32 |
| serious Total, serious adverse events | 0 / 16 | 0 / 8 | 0 / 8 | 0 / 32 | 0 / 32 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation
AEs were collected to evaluate the safety and tolerability of oral Antizol with concomitant ethanol administration in particitpants with symptoms of acetaldehyde toxicity associated with altered ethanol metabolism. AE: any untoward medical event that occurs following the first administration of study medication until the study participant's last study visit, whether or not the event is considered drug related. SAE: an event that meets any of the following criteria: results in death; is life threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in the offspring of an exposed subject; is medically significant or an important medical event as assessed by investigator or sponsor; is, in the opinion of the investigator, an important medical event.
Time frame: Study Day 0 through Study Visit Day 7
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Antizol 1.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Moderate AE | 2 Participants |
| Antizol 1.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Possibly or Probably Related AE | 13 Participants |
| Antizol 1.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Mild AE | 13 Participants |
| Antizol 1.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Serious AE | 0 Participants |
| Antizol 1.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Severe AE | 0 Participants |
| Antizol 1.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | AE Leading to Study Discontinuation | 0 Participants |
| Antizol 1.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Death | 0 Participants |
| Antizol 1.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Any AE | 13 Participants |
| Antizol 1.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Life-Threatening/Disabling AE | 0 Participants |
| Antizol 3.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Mild AE | 6 Participants |
| Antizol 3.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | AE Leading to Study Discontinuation | 0 Participants |
| Antizol 3.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Death | 0 Participants |
| Antizol 3.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Life-Threatening/Disabling AE | 0 Participants |
| Antizol 3.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Any AE | 6 Participants |
| Antizol 3.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Possibly or Probably Related AE | 6 Participants |
| Antizol 3.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Serious AE | 0 Participants |
| Antizol 3.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Moderate AE | 0 Participants |
| Antizol 3.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Severe AE | 0 Participants |
| Antizol 5.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Moderate AE | 0 Participants |
| Antizol 5.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Mild AE | 8 Participants |
| Antizol 5.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Severe AE | 0 Participants |
| Antizol 5.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Life-Threatening/Disabling AE | 0 Participants |
| Antizol 5.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Death | 0 Participants |
| Antizol 5.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Possibly or Probably Related AE | 5 Participants |
| Antizol 5.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | AE Leading to Study Discontinuation | 0 Participants |
| Antizol 5.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Serious AE | 0 Participants |
| Antizol 5.0 mg/kg | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Any AE | 8 Participants |
| Pooled Placebo | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | AE Leading to Study Discontinuation | 0 Participants |
| Pooled Placebo | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Possibly or Probably Related AE | 18 Participants |
| Pooled Placebo | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Death | 0 Participants |
| Pooled Placebo | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Any AE | 21 Participants |
| Pooled Placebo | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Life-Threatening/Disabling AE | 0 Participants |
| Pooled Placebo | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Severe AE | 0 Participants |
| Pooled Placebo | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Mild AE | 19 Participants |
| Pooled Placebo | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Moderate AE | 5 Participants |
| Pooled Placebo | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Serious AE | 0 Participants |
| Overall | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Severe AE | 0 Participants |
| Overall | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | AE Leading to Study Discontinuation | 0 Participants |
| Overall | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Any AE | 28 Participants |
| Overall | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Mild AE | 28 Participants |
| Overall | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Possibly or Probably Related AE | 27 Participants |
| Overall | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Serious AE | 0 Participants |
| Overall | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Life-Threatening/Disabling AE | 0 Participants |
| Overall | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Death | 0 Participants |
| Overall | Number of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Study Discontinuation | Moderate AE | 7 Participants |
Secondary
Pharmacokinetics (PK) of 4-MP: Maximum Plasma Concentration (Cmax)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | Pharmacokinetics (PK) of 4-MP: Maximum Plasma Concentration (Cmax) | 2386 ng/mL | Standard Deviation 625 |
| Antizol 3.0 mg/kg | Pharmacokinetics (PK) of 4-MP: Maximum Plasma Concentration (Cmax) | 1358 ng/mL | Standard Deviation 359 |
| Antizol 5.0 mg/kg | Pharmacokinetics (PK) of 4-MP: Maximum Plasma Concentration (Cmax) | 5605 ng/mL | Standard Deviation 1183 |
| Pooled Placebo | Pharmacokinetics (PK) of 4-MP: Maximum Plasma Concentration (Cmax) | 4680 ng/mL | Standard Deviation 645 |
| Overall | Pharmacokinetics (PK) of 4-MP: Maximum Plasma Concentration (Cmax) | 8623 ng/mL | Standard Deviation 2674 |
Secondary
PK of 4-MP: Apparent Clearance (CL/F)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: Apparent Clearance (CL/F) | 6.70 L/hr | — |
| Antizol 3.0 mg/kg | PK of 4-MP: Apparent Clearance (CL/F) | 8.23 L/hr | Standard Deviation 0.618 |
| Antizol 5.0 mg/kg | PK of 4-MP: Apparent Clearance (CL/F) | 3.15 L/hr | — |
| Pooled Placebo | PK of 4-MP: Apparent Clearance (CL/F) | 2.99 L/hr | — |
| Overall | PK of 4-MP: Apparent Clearance (CL/F) | 2.35 L/hr | Standard Deviation 0.782 |
Secondary
PK of 4-MP: Apparent Volume of Distribution During Terminal Phase (Vz/F)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: Apparent Volume of Distribution During Terminal Phase (Vz/F) | 26.3 Liters | — |
| Antizol 3.0 mg/kg | PK of 4-MP: Apparent Volume of Distribution During Terminal Phase (Vz/F) | 24.7 Liters | Standard Deviation 4.22 |
| Antizol 5.0 mg/kg | PK of 4-MP: Apparent Volume of Distribution During Terminal Phase (Vz/F) | 24.4 Liters | — |
| Pooled Placebo | PK of 4-MP: Apparent Volume of Distribution During Terminal Phase (Vz/F) | 24.9 Liters | — |
| Overall | PK of 4-MP: Apparent Volume of Distribution During Terminal Phase (Vz/F) | 24.7 Liters | Standard Deviation 9.91 |
Secondary
PK of 4-MP: Area Under the Plasma Concentration-Time Curve (AUC), Calculated to the Last Measured Concentration (AUC[0-t])
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: Area Under the Plasma Concentration-Time Curve (AUC), Calculated to the Last Measured Concentration (AUC[0-t]) | 13804 ng*hr/mL | Standard Deviation 4492 |
| Antizol 3.0 mg/kg | PK of 4-MP: Area Under the Plasma Concentration-Time Curve (AUC), Calculated to the Last Measured Concentration (AUC[0-t]) | 7409 ng*hr/mL | Standard Deviation 1437 |
| Antizol 5.0 mg/kg | PK of 4-MP: Area Under the Plasma Concentration-Time Curve (AUC), Calculated to the Last Measured Concentration (AUC[0-t]) | 44942 ng*hr/mL | Standard Deviation 17784 |
| Pooled Placebo | PK of 4-MP: Area Under the Plasma Concentration-Time Curve (AUC), Calculated to the Last Measured Concentration (AUC[0-t]) | 34310 ng*hr/mL | Standard Deviation 14431 |
| Overall | PK of 4-MP: Area Under the Plasma Concentration-Time Curve (AUC), Calculated to the Last Measured Concentration (AUC[0-t]) | 109298 ng*hr/mL | Standard Deviation 30635 |
Secondary
PK of 4-MP: AUC, From Time 0 Extrapolated to Infinite Time (AUC[0-∞])
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: AUC, From Time 0 Extrapolated to Infinite Time (AUC[0-∞]) | 11035 ng*hr/mL | — |
| Antizol 3.0 mg/kg | PK of 4-MP: AUC, From Time 0 Extrapolated to Infinite Time (AUC[0-∞]) | 7627 ng*hr/mL | Standard Deviation 948 |
| Antizol 5.0 mg/kg | PK of 4-MP: AUC, From Time 0 Extrapolated to Infinite Time (AUC[0-∞]) | 55452 ng*hr/mL | — |
| Pooled Placebo | PK of 4-MP: AUC, From Time 0 Extrapolated to Infinite Time (AUC[0-∞]) | 57028 ng*hr/mL | — |
| Overall | PK of 4-MP: AUC, From Time 0 Extrapolated to Infinite Time (AUC[0-∞]) | 136871 ng*hr/mL | Standard Deviation 43703 |
Secondary
PK of 4-MP: DN AUC(0-∞)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: DN AUC(0-∞) | 149 (ng*hr/mL)/mg | — |
| Antizol 3.0 mg/kg | PK of 4-MP: DN AUC(0-∞) | 122 (ng*hr/mL)/mg | Standard Deviation 9.15 |
| Antizol 5.0 mg/kg | PK of 4-MP: DN AUC(0-∞) | 317 (ng*hr/mL)/mg | — |
| Pooled Placebo | PK of 4-MP: DN AUC(0-∞) | 334 (ng*hr/mL)/mg | — |
| Overall | PK of 4-MP: DN AUC(0-∞) | 460 (ng*hr/mL)/mg | Standard Deviation 129 |
Secondary
PK of 4-MP: DN AUC(0-t)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: DN AUC(0-t) | 223 (ng*hr/mL)/mg | Standard Deviation 105 |
| Antizol 3.0 mg/kg | PK of 4-MP: DN AUC(0-t) | 103 (ng*hr/mL)/mg | Standard Deviation 16.6 |
| Antizol 5.0 mg/kg | PK of 4-MP: DN AUC(0-t) | 231 (ng*hr/mL)/mg | Standard Deviation 110 |
| Pooled Placebo | PK of 4-MP: DN AUC(0-t) | 204 (ng*hr/mL)/mg | Standard Deviation 83.1 |
| Overall | PK of 4-MP: DN AUC(0-t) | 378 (ng*hr/mL)/mg | Standard Deviation 110 |
Comparison: 1.0 mg/kg Cohort, 3.0 mg/kg cohort, 5.0 mg/kg cohortp-value: 0.0023ANOVA
Comparison: 1.0 mg/kg Cohort, 3.0 mg/kg cohortp-value: 0.386ANOVA
Comparison: 1.0 mg/kg, 5.0 mg/kgp-value: 0.0006ANOVA
Comparison: 3.0 mg/kg, 5.0 mg/kgp-value: 0.0154ANOVA
Secondary
PK of 4-MP: Dose-Normalized (DN) Cmax
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: Dose-Normalized (DN) Cmax | 38.3 (ng/mL)/mg | Standard Deviation 15.9 |
| Antizol 3.0 mg/kg | PK of 4-MP: Dose-Normalized (DN) Cmax | 18.9 (ng/mL)/mg | Standard Deviation 4.65 |
| Antizol 5.0 mg/kg | PK of 4-MP: Dose-Normalized (DN) Cmax | 27.6 (ng/mL)/mg | Standard Deviation 3.05 |
| Pooled Placebo | PK of 4-MP: Dose-Normalized (DN) Cmax | 28.0 (ng/mL)/mg | Standard Deviation 4.26 |
| Overall | PK of 4-MP: Dose-Normalized (DN) Cmax | 30.2 (ng/mL)/mg | Standard Deviation 11 |
Comparison: 1.0 mg/kg Cohort, 3.0 mg/kg cohort, 5.0 mg/kg cohortp-value: 0.8727ANOVA
Secondary
PK of 4-MP: Half-Life (T1/2)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: Half-Life (T1/2) | 2.72 hours | — |
| Antizol 3.0 mg/kg | PK of 4-MP: Half-Life (T1/2) | 3.11 hours | Standard Deviation 1.8 |
| Antizol 5.0 mg/kg | PK of 4-MP: Half-Life (T1/2) | 5.37 hours | — |
| Pooled Placebo | PK of 4-MP: Half-Life (T1/2) | 5.76 hours | — |
| Overall | PK of 4-MP: Half-Life (T1/2) | 9.26 hours | Standard Deviation 4.93 |
Secondary
PK of 4-MP: Percentage of AUC0-∞ Obtained by Extrapolation (AUC%Extrap)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: Percentage of AUC0-∞ Obtained by Extrapolation (AUC%Extrap) | 16.8 percentage | — |
| Antizol 3.0 mg/kg | PK of 4-MP: Percentage of AUC0-∞ Obtained by Extrapolation (AUC%Extrap) | 13.0 percentage | Standard Deviation 0.606 |
| Antizol 5.0 mg/kg | PK of 4-MP: Percentage of AUC0-∞ Obtained by Extrapolation (AUC%Extrap) | 3.31 percentage | — |
| Pooled Placebo | PK of 4-MP: Percentage of AUC0-∞ Obtained by Extrapolation (AUC%Extrap) | 4.37 percentage | — |
| Overall | PK of 4-MP: Percentage of AUC0-∞ Obtained by Extrapolation (AUC%Extrap) | 13.2 percentage | Standard Deviation 12.6 |
Secondary
PK of 4-MP: Time to Cmax (Tmax)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Antizol 1.0 mg/kg | PK of 4-MP: Time to Cmax (Tmax) | 1.00 hours |
| Antizol 3.0 mg/kg | PK of 4-MP: Time to Cmax (Tmax) | 2.50 hours |
| Antizol 5.0 mg/kg | PK of 4-MP: Time to Cmax (Tmax) | 0.667 hours |
| Pooled Placebo | PK of 4-MP: Time to Cmax (Tmax) | 1.48 hours |
| Overall | PK of 4-MP: Time to Cmax (Tmax) | 1.00 hours |
Secondary
PK of Acetaldehyde: AUC(0-∞)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Acetaldehyde: AUC(0-∞) | 234 µM*hr | Standard Deviation 64.4 |
| Antizol 3.0 mg/kg | PK of Acetaldehyde: AUC(0-∞) | 154 µM*hr | Standard Deviation 63.3 |
| Antizol 5.0 mg/kg | PK of Acetaldehyde: AUC(0-∞) | 297 µM*hr | — |
| Pooled Placebo | PK of Acetaldehyde: AUC(0-∞) | 302 µM*hr | — |
| Overall | PK of Acetaldehyde: AUC(0-∞) | 188 µM*hr | Standard Deviation 28.1 |
| Placebo Followed by Ethanol | PK of Acetaldehyde: AUC(0-∞) | 205 µM*hr | Standard Deviation 71.1 |
| Ethanol Followed by Placebo | PK of Acetaldehyde: AUC(0-∞) | 227 µM*hr | Standard Deviation 92.9 |
90% CI: [78.01, 1113.63]
Comparison: 3 participants in Cohort 3 had some residual 4-MP detected on Day 2 (Placebo treatment). As a result, the data for the participants on Day 2 were excluded from these statistical analyses, which could be compared with the analyses below where all available data were included.90% CI: [87.42, 131.1]
Comparison: Analyses for Cohort 3 where all available data were included.90% CI: [84.84, 112.97]
Secondary
PK of Acetaldehyde: AUC(0-t)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Acetaldehyde: AUC(0-t) | 178 µM*hr | Standard Deviation 53 |
| Antizol 3.0 mg/kg | PK of Acetaldehyde: AUC(0-t) | 118 µM*hr | Standard Deviation 56.4 |
| Antizol 5.0 mg/kg | PK of Acetaldehyde: AUC(0-t) | 155 µM*hr | Standard Deviation 68.7 |
| Pooled Placebo | PK of Acetaldehyde: AUC(0-t) | 167 µM*hr | Standard Deviation 84.4 |
| Overall | PK of Acetaldehyde: AUC(0-t) | 128 µM*hr | Standard Deviation 33.2 |
| Placebo Followed by Ethanol | PK of Acetaldehyde: AUC(0-t) | 163 µM*hr | Standard Deviation 61.3 |
| Ethanol Followed by Placebo | PK of Acetaldehyde: AUC(0-t) | 139 µM*hr | Standard Deviation 93.7 |
90% CI: [69.54, 117]
90% CI: [103.72, 121.54]
90% CI: [96.81, 116.24]
90% CI: [83.5, 129.84]
Comparison: 3 participants in Cohort 3 had some residual 4-MP detected on Day 2 (Placebo treatment). As a result, the data for the participants on Day 2 were excluded from these statistical analyses, which could be compared with the analyses below where all available data were included.90% CI: [77.86, 129.49]
Comparison: Analyses for Cohort 3 where all available data were included.90% CI: [82.7, 108.42]
Secondary
PK of Acetaldehyde: AUC%Extrap
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Acetaldehyde: AUC%Extrap | 19.0 percentage | Standard Deviation 6.07 |
| Antizol 3.0 mg/kg | PK of Acetaldehyde: AUC%Extrap | 18.8 percentage | Standard Deviation 8.11 |
| Antizol 5.0 mg/kg | PK of Acetaldehyde: AUC%Extrap | 13.1 percentage | — |
| Pooled Placebo | PK of Acetaldehyde: AUC%Extrap | 9.78 percentage | — |
| Overall | PK of Acetaldehyde: AUC%Extrap | 24.7 percentage | Standard Deviation 5.26 |
| Placebo Followed by Ethanol | PK of Acetaldehyde: AUC%Extrap | 13.7 percentage | Standard Deviation 5.29 |
| Ethanol Followed by Placebo | PK of Acetaldehyde: AUC%Extrap | 14.5 percentage | Standard Deviation 11.4 |
Secondary
PK of Acetaldehyde: Cmax
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Acetaldehyde: Cmax | 59.6 µM | Standard Deviation 34.4 |
| Antizol 3.0 mg/kg | PK of Acetaldehyde: Cmax | 37.6 µM | Standard Deviation 26.9 |
| Antizol 5.0 mg/kg | PK of Acetaldehyde: Cmax | 50.9 µM | Standard Deviation 52.8 |
| Pooled Placebo | PK of Acetaldehyde: Cmax | 55.9 µM | Standard Deviation 52.2 |
| Overall | PK of Acetaldehyde: Cmax | 40.0 µM | Standard Deviation 16.6 |
| Placebo Followed by Ethanol | PK of Acetaldehyde: Cmax | 60.3 µM | Standard Deviation 34.8 |
| Ethanol Followed by Placebo | PK of Acetaldehyde: Cmax | 42.7 µM | Standard Deviation 30.6 |
90% CI: [48.88, 97.78]
90% CI: [88.77, 174.5]
90% CI: [89.24, 124.27]
90% CI: [56.66, 138.54]
Comparison: 3 participants in Cohort 3 had some residual 4-MP detected on Day 2 (Placebo treatment). As a result, the data for the participants on Day 2 were excluded from these statistical analyses, which could be compared with the analyses below where all available data were included.90% CI: [34.16, 146.59]
Comparison: Analyses for Cohort 3 where all available data were included.90% CI: [55.78, 132.73]
Secondary
PK of Acetaldehyde: DN AUC(0-∞)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Acetaldehyde: DN AUC(0-∞) | 0.00682 µM*hr/mg | Standard Deviation 0.00203 |
| Antizol 3.0 mg/kg | PK of Acetaldehyde: DN AUC(0-∞) | 0.00432 µM*hr/mg | Standard Deviation 0.00176 |
| Antizol 5.0 mg/kg | PK of Acetaldehyde: DN AUC(0-∞) | 0.00929 µM*hr/mg | — |
| Pooled Placebo | PK of Acetaldehyde: DN AUC(0-∞) | 0.0105 µM*hr/mg | — |
| Overall | PK of Acetaldehyde: DN AUC(0-∞) | 0.00626 µM*hr/mg | Standard Deviation 0.0011 |
| Placebo Followed by Ethanol | PK of Acetaldehyde: DN AUC(0-∞) | 0.00616 µM*hr/mg | Standard Deviation 0.00171 |
| Ethanol Followed by Placebo | PK of Acetaldehyde: DN AUC(0-∞) | 0.00752 µM*hr/mg | Standard Deviation 0.0036 |
Secondary
PK of Acetaldehyde: DN AUC(0-t)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Acetaldehyde: DN AUC(0-t) | 0.00547 µM*hr/mg | Standard Deviation 0.00148 |
| Antizol 3.0 mg/kg | PK of Acetaldehyde: DN AUC(0-t) | 0.00329 µM*hr/mg | Standard Deviation 0.00144 |
| Antizol 5.0 mg/kg | PK of Acetaldehyde: DN AUC(0-t) | 0.00470 µM*hr/mg | Standard Deviation 0.0023 |
| Pooled Placebo | PK of Acetaldehyde: DN AUC(0-t) | 0.00597 µM*hr/mg | Standard Deviation 0.00293 |
| Overall | PK of Acetaldehyde: DN AUC(0-t) | 0.00439 µM*hr/mg | Standard Deviation 0.001 |
| Placebo Followed by Ethanol | PK of Acetaldehyde: DN AUC(0-t) | 0.00521 µM*hr/mg | Standard Deviation 0.00204 |
| Ethanol Followed by Placebo | PK of Acetaldehyde: DN AUC(0-t) | 0.00455 µM*hr/mg | Standard Deviation 0.00332 |
Secondary
PK of Acetaldehyde: DN Cmax
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Acetaldehyde: DN Cmax | 0.00181 µM/mg | Standard Deviation 0.00101 |
| Antizol 3.0 mg/kg | PK of Acetaldehyde: DN Cmax | 0.00104 µM/mg | Standard Deviation 0.00065 |
| Antizol 5.0 mg/kg | PK of Acetaldehyde: DN Cmax | 0.00157 µM/mg | Standard Deviation 0.00167 |
| Pooled Placebo | PK of Acetaldehyde: DN Cmax | 0.00201 µM/mg | Standard Deviation 0.00192 |
| Overall | PK of Acetaldehyde: DN Cmax | 0.00138 µM/mg | Standard Deviation 0.000542 |
| Placebo Followed by Ethanol | PK of Acetaldehyde: DN Cmax | 0.00193 µM/mg | Standard Deviation 0.00114 |
| Ethanol Followed by Placebo | PK of Acetaldehyde: DN Cmax | 0.00141 µM/mg | Standard Deviation 0.00112 |
Secondary
PK of Acetaldehyde: T1/2
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Acetaldehyde: T1/2 | 3.14 hours | Standard Deviation 0.729 |
| Antizol 3.0 mg/kg | PK of Acetaldehyde: T1/2 | 3.08 hours | Standard Deviation 0.64 |
| Antizol 5.0 mg/kg | PK of Acetaldehyde: T1/2 | 2.48 hours | — |
| Pooled Placebo | PK of Acetaldehyde: T1/2 | 1.72 hours | — |
| Overall | PK of Acetaldehyde: T1/2 | 3.45 hours | Standard Deviation 3.43 |
| Placebo Followed by Ethanol | PK of Acetaldehyde: T1/2 | 2.39 hours | Standard Deviation 0.521 |
| Ethanol Followed by Placebo | PK of Acetaldehyde: T1/2 | 2.09 hours | Standard Deviation 0.895 |
Secondary
PK of Acetaldehyde: Tmax
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Antizol 1.0 mg/kg | PK of Acetaldehyde: Tmax | 0.500 hours |
| Antizol 3.0 mg/kg | PK of Acetaldehyde: Tmax | 0.650 hours |
| Antizol 5.0 mg/kg | PK of Acetaldehyde: Tmax | 1.00 hours |
| Pooled Placebo | PK of Acetaldehyde: Tmax | 1.33 hours |
| Overall | PK of Acetaldehyde: Tmax | 0.500 hours |
| Placebo Followed by Ethanol | PK of Acetaldehyde: Tmax | 0.500 hours |
| Ethanol Followed by Placebo | PK of Acetaldehyde: Tmax | 0.925 hours |
Secondary
PK of Ethanol: AUC(0-∞)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: AUC(0-∞) | 245 mg*hr/mL | Standard Deviation 55.7 |
| Antizol 3.0 mg/kg | PK of Ethanol: AUC(0-∞) | 263 mg*hr/mL | Standard Deviation 27.2 |
| Antizol 5.0 mg/kg | PK of Ethanol: AUC(0-∞) | 237 mg*hr/mL | Standard Deviation 27 |
| Pooled Placebo | PK of Ethanol: AUC(0-∞) | 215 mg*hr/mL | Standard Deviation 27.9 |
| Overall | PK of Ethanol: AUC(0-∞) | 271 mg*hr/mL | Standard Deviation 75 |
| Placebo Followed by Ethanol | PK of Ethanol: AUC(0-∞) | 214 mg*hr/mL | Standard Deviation 47.4 |
| Ethanol Followed by Placebo | PK of Ethanol: AUC(0-∞) | 198 mg*hr/mL | Standard Deviation 47.3 |
90% CI: [108.42, 136.84]
90% CI: [93.55, 163.56]
90% CI: [93.14, 242.63]
Comparison: Analysis for Cohort 3 where all available data were included.90% CI: [82.45, 183]
Secondary
PK of Ethanol: AUC(0-t)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: AUC(0-t) | 209 mg*hr/dL | Standard Deviation 46.1 |
| Antizol 3.0 mg/kg | PK of Ethanol: AUC(0-t) | 209 mg*hr/dL | Standard Deviation 24.2 |
| Antizol 5.0 mg/kg | PK of Ethanol: AUC(0-t) | 205 mg*hr/dL | Standard Deviation 13.1 |
| Pooled Placebo | PK of Ethanol: AUC(0-t) | 135 mg*hr/dL | Standard Deviation 44 |
| Overall | PK of Ethanol: AUC(0-t) | 231 mg*hr/dL | Standard Deviation 67.1 |
| Placebo Followed by Ethanol | PK of Ethanol: AUC(0-t) | 157 mg*hr/dL | Standard Deviation 53.2 |
| Ethanol Followed by Placebo | PK of Ethanol: AUC(0-t) | 152 mg*hr/dL | Standard Deviation 42.6 |
90% CI: [92.18, 211.51]
90% CI: [108.8, 134.03]
90% CI: [107.72, 190.87]
90% CI: [84.35, 126.1]
Comparison: 3 participants in Cohort 3 had some residual 4-MP detected on Day 2 (Placebo treatment). As a result, the data for the participants on Day 2 were excluded from these statistical analyses, which could be compared with the analyses below where all available data were included.90% CI: [108.61, 139.67]
Comparison: Analyses for Cohort 3 where all available data were included.90% CI: [123.3, 152.59]
Secondary
PK of Ethanol: AUC%Extrap
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: AUC%Extrap | 14.7 percentage | Standard Deviation 4.95 |
| Antizol 3.0 mg/kg | PK of Ethanol: AUC%Extrap | 20.5 percentage | Standard Deviation 6.9 |
| Antizol 5.0 mg/kg | PK of Ethanol: AUC%Extrap | 13.2 percentage | Standard Deviation 4.89 |
| Pooled Placebo | PK of Ethanol: AUC%Extrap | 20.0 percentage | Standard Deviation 4.68 |
| Overall | PK of Ethanol: AUC%Extrap | 12.1 percentage | Standard Deviation 6.13 |
| Placebo Followed by Ethanol | PK of Ethanol: AUC%Extrap | 13.4 percentage | Standard Deviation 5.62 |
| Ethanol Followed by Placebo | PK of Ethanol: AUC%Extrap | 13.9 percentage | Standard Deviation 4.85 |
Secondary
PK of Ethanol: CL/F
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: CL/F | 140 dL/hr | Standard Deviation 36.8 |
| Antizol 3.0 mg/kg | PK of Ethanol: CL/F | 138 dL/hr | Standard Deviation 14.3 |
| Antizol 5.0 mg/kg | PK of Ethanol: CL/F | 142 dL/hr | Standard Deviation 8.81 |
| Pooled Placebo | PK of Ethanol: CL/F | 131 dL/hr | Standard Deviation 12 |
| Overall | PK of Ethanol: CL/F | 112 dL/hr | Standard Deviation 19.6 |
| Placebo Followed by Ethanol | PK of Ethanol: CL/F | 159 dL/hr | Standard Deviation 51.8 |
| Ethanol Followed by Placebo | PK of Ethanol: CL/F | 167 dL/hr | Standard Deviation 32.7 |
Secondary
PK of Ethanol: Cmax
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: Cmax | 62.7 mg/dL | Standard Deviation 10.1 |
| Antizol 3.0 mg/kg | PK of Ethanol: Cmax | 70.3 mg/dL | Standard Deviation 4.99 |
| Antizol 5.0 mg/kg | PK of Ethanol: Cmax | 80.5 mg/dL | Standard Deviation 5.2 |
| Pooled Placebo | PK of Ethanol: Cmax | 43.3 mg/dL | Standard Deviation 9.54 |
| Overall | PK of Ethanol: Cmax | 74.9 mg/dL | Standard Deviation 21.9 |
| Placebo Followed by Ethanol | PK of Ethanol: Cmax | 59.3 mg/dL | Standard Deviation 15.4 |
| Ethanol Followed by Placebo | PK of Ethanol: Cmax | 55.1 mg/dL | Standard Deviation 14.5 |
90% CI: [90.45, 147.67]
90% CI: [101.94, 155.87]
90% CI: [115.66, 163.65]
90% CI: [62.83, 108.07]
Comparison: 3 participants in Cohort 3 had some residual 4-MP detected on Day 2 (Placebo treatment). As a result, the data for the participants on Day 2 were excluded from these statistical analyses, which could be compared with the analyses below where all available data were included.90% CI: [91.19, 145.67]
Comparison: Analyses for Cohort 3 where all available data were included.90% CI: [96.14, 131.98]
Secondary
PK of Ethanol: DN AUC(0-∞)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: DN AUC(0-∞) | 0.00760 (mg*hr/dL)/mg | Standard Deviation 0.00199 |
| Antizol 3.0 mg/kg | PK of Ethanol: DN AUC(0-∞) | 0.00731 (mg*hr/dL)/mg | Standard Deviation 0.000843 |
| Antizol 5.0 mg/kg | PK of Ethanol: DN AUC(0-∞) | 0.00705 (mg*hr/dL)/mg | Standard Deviation 0.000437 |
| Pooled Placebo | PK of Ethanol: DN AUC(0-∞) | 0.00768 (mg*hr/dL)/mg | Standard Deviation 0.000707 |
| Overall | PK of Ethanol: DN AUC(0-∞) | 0.00917 (mg*hr/dL)/mg | Standard Deviation 0.00166 |
| Placebo Followed by Ethanol | PK of Ethanol: DN AUC(0-∞) | 0.00681 (mg*hr/dL)/mg | Standard Deviation 0.00182 |
| Ethanol Followed by Placebo | PK of Ethanol: DN AUC(0-∞) | 0.00617 (mg*hr/dL)/mg | Standard Deviation 0.0012 |
Secondary
PK of Ethanol: DN AUC(0-t)
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: DN AUC(0-t) | 0.00648 (mg*hr/dL)/mg | Standard Deviation 0.00171 |
| Antizol 3.0 mg/kg | PK of Ethanol: DN AUC(0-t) | 0.00585 (mg*hr/dL)/mg | Standard Deviation 0.00115 |
| Antizol 5.0 mg/kg | PK of Ethanol: DN AUC(0-t) | 0.00613 (mg*hr/dL)/mg | Standard Deviation 0.000641 |
| Pooled Placebo | PK of Ethanol: DN AUC(0-t) | 0.00483 (mg*hr/dL)/mg | Standard Deviation 0.00155 |
| Overall | PK of Ethanol: DN AUC(0-t) | 0.00791 (mg*hr/dL)/mg | Standard Deviation 0.00163 |
| Placebo Followed by Ethanol | PK of Ethanol: DN AUC(0-t) | 0.00508 (mg*hr/dL)/mg | Standard Deviation 0.00194 |
| Ethanol Followed by Placebo | PK of Ethanol: DN AUC(0-t) | 0.00476 (mg*hr/dL)/mg | Standard Deviation 0.00124 |
Secondary
PK of Ethanol: DN Cmax
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: DN Cmax | 0.00195 (mg/dL)/mg | Standard Deviation 0.000448 |
| Antizol 3.0 mg/kg | PK of Ethanol: DN Cmax | 0.00198 (mg/dL)/mg | Standard Deviation 0.00042 |
| Antizol 5.0 mg/kg | PK of Ethanol: DN Cmax | 0.00243 (mg/dL)/mg | Standard Deviation 0.000453 |
| Pooled Placebo | PK of Ethanol: DN Cmax | 0.00155 (mg/dL)/mg | Standard Deviation 0.000359 |
| Overall | PK of Ethanol: DN Cmax | 0.00261 (mg/dL)/mg | Standard Deviation 0.000871 |
| Placebo Followed by Ethanol | PK of Ethanol: DN Cmax | 0.00193 (mg/dL)/mg | Standard Deviation 0.000667 |
| Ethanol Followed by Placebo | PK of Ethanol: DN Cmax | 0.00175 (mg/dL)/mg | Standard Deviation 0.000543 |
Secondary
PK of Ethanol: T1/2
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: T1/2 | 1.51 hours | Standard Deviation 0.391 |
| Antizol 3.0 mg/kg | PK of Ethanol: T1/2 | 1.95 hours | Standard Deviation 0.206 |
| Antizol 5.0 mg/kg | PK of Ethanol: T1/2 | 1.43 hours | Standard Deviation 0.219 |
| Pooled Placebo | PK of Ethanol: T1/2 | 1.78 hours | Standard Deviation 0.64 |
| Overall | PK of Ethanol: T1/2 | 1.67 hours | Standard Deviation 0.608 |
| Placebo Followed by Ethanol | PK of Ethanol: T1/2 | 1.45 hours | Standard Deviation 0.564 |
| Ethanol Followed by Placebo | PK of Ethanol: T1/2 | 1.32 hours | Standard Deviation 0.193 |
Secondary
PK of Ethanol: Tmax
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure and who received study assessments through Study Day 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: Tmax | 1.50 hours |
| Antizol 3.0 mg/kg | PK of Ethanol: Tmax | 0.833 hours |
| Antizol 5.0 mg/kg | PK of Ethanol: Tmax | 0.500 hours |
| Pooled Placebo | PK of Ethanol: Tmax | 1.42 hours |
| Overall | PK of Ethanol: Tmax | 0.500 hours |
| Placebo Followed by Ethanol | PK of Ethanol: Tmax | 0.500 hours |
| Ethanol Followed by Placebo | PK of Ethanol: Tmax | 1.01 hours |
Secondary
PK of Ethanol: Vz/F
Time frame: Days 1 and 2: prior to administration of 1st treatment (ethanol or study drug); 10, 20, and 30 min prior to administration of second treatment (study drug or ethanol); 40, 50, 60 min and 2, 3, 4, 5, 6, and 8 hr post administration of 1st treatment
Population: Modified Intent-to-Treat: participants who received any study medication or procedure, received study assessments through Study Day 2, and who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antizol 1.0 mg/kg | PK of Ethanol: Vz/F | 297 dL | Standard Deviation 82.8 |
| Antizol 3.0 mg/kg | PK of Ethanol: Vz/F | 387 dL | Standard Deviation 57 |
| Antizol 5.0 mg/kg | PK of Ethanol: Vz/F | 295 dL | Standard Deviation 55.4 |
| Pooled Placebo | PK of Ethanol: Vz/F | 330 dL | Standard Deviation 89.5 |
| Overall | PK of Ethanol: Vz/F | 242 dL | Standard Deviation 79.1 |
| Placebo Followed by Ethanol | PK of Ethanol: Vz/F | 287 dL | Standard Deviation 86.3 |
| Ethanol Followed by Placebo | PK of Ethanol: Vz/F | 321 dL | Standard Deviation 87.7 |