Trial Outcomes & Findings for A Study to Test the Pharmacodynamic, Pharmacokinetic, Safety, and Tolerability of Padsevonil in Healthy Study Participants Receiving Either Ethanol or Cannabidiol (NCT NCT04039919)

Last Updated: 2021-06-18

Results Overview

Smooth pursuit to assess eye movement coordination and attention to evaluate the ethanol effect. The average percentage of smooth pursuit for all stimulus frequencies was used as a parameter. Participants received either ethanol or placebo on Day 1 of Period 1 or on Day 3 of Period 2. Therefore, the results were summarized by treatment.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

40 participants

Primary outcome timeframe

Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2

Results posted on

2021-06-18

Participant Flow

The study started to enroll participants in July 2019 and concluded in May 2020.

Participant Flow refers to the All Study Participants Set which included all participants who have signed the Informed Consent form (ICF).

Participant milestones

Participant milestones
Measure	Part A: Treatment Sequence A Participants received ethanol 0.6 grams per liter (g/L) intravenous (IV) infusion on Day 1 during Treatment Period 1 (TP1), followed by placebo (for ethanol IV infusion) on Day 1 during TP2, then padsevonil (PSL) oral tablets 100 mg or 200 mg BID on Day 1 to 4 during TP3, PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4, PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5, and then PSL 100 mg BID oral tablets on Day 9 during TP6. There was a washout of at least 2 days between Treatment Periods 2 and 3.	Part A: Treatment Sequence B Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1, followed by placebo (for ethanol IV infusion) on Day 1 during TP2, then PSL oral tablets 100 mg or 200 mg BID on Day 1 to 4 during TP3, PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 5 during TP4, PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 7 during TP5, and then PSL 100 mg BID oral tablets on Day 9 during TP6. There was a washout of at least 2 days between Treatment Periods 2 and 3.	Part A: Treatment Sequence C Participants received placebo (for ethanol IV infusion) on Day 1 during TP1, followed by ethanol 0.6 g/L IV infusion on Day 1 during TP2, then PSL oral tablets 100 mg or 200 mg BID on Day 1 to 4 during TP3, PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4, PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5, and then PSL 100 mg BID oral tablets on Day 9 during TP6. There was a washout of at least 2 days between Treatment Periods 2 and 3.	Part A: Treatment Sequence D Participants received placebo (for ethanol IV infusion) on Day 1 during TP1, followed by ethanol 0.6 g/L IV infusion on Day 1 during TP2, then PSL oral tablets 100 mg or 200 mg BID on Day 1 to 4 during TP3, PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 5 during TP4, PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 7 during TP5, and then PSL 100 mg BID oral tablets on Day 9 during TP6. There was a washout of at least 2 days between Treatment Periods 2 and 3.	Part B: Cannabidiol (CBD) Participants received a single oral dose of CBD 10 milligrams per kilogram (mg/kg) solution, under fasted condition on Day 1 during TP1.
Treatment Period 1 STARTED	7	6	5	6	16
Treatment Period 1 COMPLETED	6	6	5	6	0
Treatment Period 1 NOT COMPLETED	1	0	0	0	16
Treatment Period 2 STARTED	6	6	5	6	0
Treatment Period 2 COMPLETED	6	6	5	6	0
Treatment Period 2 NOT COMPLETED	0	0	0	0	0
Treatment Period 3 STARTED	6	6	5	6	0
Treatment Period 3 COMPLETED	6	6	5	6	0
Treatment Period 3 NOT COMPLETED	0	0	0	0	0
Treatment Period 4 STARTED	6	6	5	6	0
Treatment Period 4 COMPLETED	6	6	5	6	0
Treatment Period 4 NOT COMPLETED	0	0	0	0	0
Treatment Period 5 STARTED	6	6	5	6	0
Treatment Period 5 COMPLETED	5	6	5	6	0
Treatment Period 5 NOT COMPLETED	1	0	0	0	0
Treatment Period 6 STARTED	5	6	5	6	0
Treatment Period 6 COMPLETED	5	6	5	6	0
Treatment Period 6 NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Treatment Sequence A Participants received ethanol 0.6 grams per liter (g/L) intravenous (IV) infusion on Day 1 during Treatment Period 1 (TP1), followed by placebo (for ethanol IV infusion) on Day 1 during TP2, then padsevonil (PSL) oral tablets 100 mg or 200 mg BID on Day 1 to 4 during TP3, PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4, PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5, and then PSL 100 mg BID oral tablets on Day 9 during TP6. There was a washout of at least 2 days between Treatment Periods 2 and 3.	Part B: Cannabidiol (CBD) Participants received a single oral dose of CBD 10 milligrams per kilogram (mg/kg) solution, under fasted condition on Day 1 during TP1.
Treatment Period 1 Withdrawal by Subject	1	0
Treatment Period 1 Sponsor's decision	0	16
Treatment Period 5 Withdrawal by Subject	1	0

Baseline Characteristics

A Study to Test the Pharmacodynamic, Pharmacokinetic, Safety, and Tolerability of Padsevonil in Healthy Study Participants Receiving Either Ethanol or Cannabidiol

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Treatment Sequence A n=7 Participants Participants received ethanol 0.6 grams per liter (g/L) intravenous (IV) infusion on Day 1 during Treatment Period 1 (TP1), followed by placebo (for ethanol IV infusion) on Day 1 during TP2, then padsevonil (PSL) oral tablets 100 mg or 200 mg BID on Day 1 to 4 during TP3, PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4, PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5, and then PSL 100 mg BID oral tablets on Day 9 during TP6. There was a washout of at least 2 days between Treatment Periods 2 and 3.	Part A: Treatment Sequence B n=6 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1, followed by placebo (for ethanol IV infusion) on Day 1 during TP2, then PSL oral tablets 100 mg or 200 mg BID on Day 1 to 4 during TP3, PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 5 during TP4, PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 7 during TP5, and then PSL 100 mg BID oral tablets on Day 9 during TP6. There was a washout of at least 2 days between Treatment Periods 2 and 3.	Part A: Treatment Sequence C n=5 Participants Participants received placebo (for ethanol IV infusion) on Day 1 during TP1, followed by ethanol 0.6 g/L IV infusion on Day 1 during TP2, then PSL oral tablets 100 mg or 200 mg BID on Day 1 to 4 during TP3, PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4, PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5, and then PSL 100 mg BID oral tablets on Day 9 during TP6. There was a washout of at least 2 days between Treatment Periods 2 and 3.	Part A: Treatment Sequence D n=6 Participants Participants received placebo (for ethanol IV infusion) on Day 1 during TP1, followed by ethanol 0.6 g/L IV infusion on Day 1 during TP2, then PSL oral tablets 100 mg or 200 mg BID on Day 1 to 4 during TP3, PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 5 during TP4, PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 7 during TP5, and then PSL 100 mg BID oral tablets on Day 9 during TP6. There was a washout of at least 2 days between Treatment Periods 2 and 3.	Part B: Cannabidiol (CBD) n=16 Participants Participants received a single oral dose of CBD 10 milligrams per kilogram (mg/kg) solution, under fasted condition on Day 1 during TP1.	Total Title n=40 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	16 Participants n=21 Participants	40 Participants n=10 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Age, Continuous	30.3 years STANDARD_DEVIATION 9.9 • n=5 Participants	30.8 years STANDARD_DEVIATION 9.1 • n=7 Participants	28.4 years STANDARD_DEVIATION 7.0 • n=5 Participants	30.7 years STANDARD_DEVIATION 4.1 • n=4 Participants	27.9 years STANDARD_DEVIATION 9.3 • n=21 Participants	29.2 years STANDARD_DEVIATION 8.2 • n=10 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	11 Participants n=21 Participants	18 Participants n=10 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	5 Participants n=21 Participants	22 Participants n=10 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	15 Participants n=21 Participants	36 Participants n=10 Participants
Race/Ethnicity, Customized Other or Mixed	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2

Population: Full Analysis Set (FAS) consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation. Here, n (number analyzed) signifies participants evaluable at specified time points only.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=24 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=23 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A Predose	44.838 percentage of eye movements Standard Deviation 9.110	43.252 percentage of eye movements Standard Deviation 8.688	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A 0.5 hour	38.046 percentage of eye movements Standard Deviation 8.674	43.661 percentage of eye movements Standard Deviation 9.345	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A 1 hour	37.604 percentage of eye movements Standard Deviation 8.574	43.748 percentage of eye movements Standard Deviation 10.298	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A 2 hours	37.300 percentage of eye movements Standard Deviation 8.778	42.930 percentage of eye movements Standard Deviation 9.636	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A 3 hours	36.726 percentage of eye movements Standard Deviation 7.441	42.809 percentage of eye movements Standard Deviation 10.639	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A 4 hours	36.822 percentage of eye movements Standard Deviation 8.405	42.478 percentage of eye movements Standard Deviation 9.351	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A 5 hours	35.913 percentage of eye movements Standard Deviation 7.359	42.622 percentage of eye movements Standard Deviation 9.200	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A 6 hours	40.570 percentage of eye movements Standard Deviation 9.353	43.300 percentage of eye movements Standard Deviation 8.960	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A 8 hours	41.948 percentage of eye movements Standard Deviation 10.245	44.026 percentage of eye movements Standard Deviation 10.085	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A 10 hours	43.491 percentage of eye movements Standard Deviation 8.928	43.504 percentage of eye movements Standard Deviation 11.394	—	—	—	—

PRIMARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 5 of Period 4 or Day 7 of Period 5

Population: FAS consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation. Here, Number of participants analyzed signifies participants who were evaluable for the assessment.

Smooth pursuit to assess eye movement coordination and attention to evaluate the ethanol effect. The average percentage of smooth pursuit for all stimulus frequencies was used as a parameter. Participants received either ethanol or placebo on Day 5 of Period 4 or Day 7 of Period 5. Therefore, the results were summarized by treatment.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=23 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=22 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A Predose	41.107 percentage of eye movements Standard Deviation 9.930	41.402 percentage of eye movements Standard Deviation 8.500	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A 0.5 hour	32.591 percentage of eye movements Standard Deviation 7.140	39.655 percentage of eye movements Standard Deviation 9.703	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A 1 hour	30.874 percentage of eye movements Standard Deviation 6.790	35.814 percentage of eye movements Standard Deviation 7.893	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A 2 hours	28.309 percentage of eye movements Standard Deviation 5.321	36.036 percentage of eye movements Standard Deviation 9.172	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A 3 hours	28.530 percentage of eye movements Standard Deviation 6.881	36.727 percentage of eye movements Standard Deviation 9.512	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A 4 hours	30.400 percentage of eye movements Standard Deviation 9.466	36.668 percentage of eye movements Standard Deviation 8.411	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A 5 hours	30.239 percentage of eye movements Standard Deviation 6.750	35.714 percentage of eye movements Standard Deviation 8.865	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A 6 hours	33.761 percentage of eye movements Standard Deviation 8.383	38.945 percentage of eye movements Standard Deviation 9.676	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A 8 hours	35.604 percentage of eye movements Standard Deviation 8.894	37.973 percentage of eye movements Standard Deviation 8.849	—	—	—	—
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A 10 hours	38.570 percentage of eye movements Standard Deviation 10.683	38.591 percentage of eye movements Standard Deviation 9.508	—	—	—	—

PRIMARY outcome

Timeframe: Predose up to 12 hours postdose

Population: Analysis of this outcome measure was not performed because the study was terminated. At that time, Part A had been completed, and 16 study participants had been treated with CBD in Treatment Period 1 of Part B.

Cmax is maximum observed plasma concentration at steady state of padsevonil.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Predose up to 12 hours postdose

Population: Pharmacokinetic Set (PKS) included all study participants that received at least one dose of active study drug and have at least one observable pharmacokinetic measurement.

Cmax is maximum observed plasma concentration at steady state of CBD.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=16 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Cannabidiol During Part B	NA nanograms per milliliter Analysis of this outcome measure was not performed because the study was terminated. At that time, Part A had been completed, and 16 study participants had been treated with CBD in Treatment Period 1 of Part B.	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose up to 12 hours post dose

AUCtau is the area under the curve over a dosing interval of padsevonil.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Predose up to 12 hours postdose

Population: PKS included all study participants that received at least one dose of active study drug and have at least one observable pharmacokinetic measurement.

AUCtau is the area under the curve over a dosing interval of CBD.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=16 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Area Under the Curve Over a Dosing Interval (AUCtau) of Cannabidiol During Part B	NA hours*nanogram per milliliter Analysis of this outcome measure was not performed because the study was terminated. At that time, Part A had been completed, and 16 study participants had been treated with CBD in Treatment Period 1 of Part B.	—	—	—	—	—

SECONDARY outcome

Timeframe: -0.4, -0.3, -0.2, -0.16, -0.08, Predose, 0.16, 0.3, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7 and 8 hours postdose on Day 1 of Period 1 or on Day 3 of Period 2

Population: PKS included all study participants that received at least one dose of active study drug and have at least one observable pharmacokinetic measurement.

Continuous infusion of ethanol began with a 30 minute loading phase (prior to 0 hours) and was continued for 5 hours with adjustments during the infusion. Participants received either ethanol on Day 1 of Period 1 or on Day 3 of Period 2. Therefore, the results were summarized by treatment.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=21 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A -0.4 hour	0.290 grams per liter Interval 0.254 to 0.333	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A -0.3 hour	0.428 grams per liter Interval 0.379 to 0.483	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A -0.2 hour	0.477 grams per liter Interval 0.446 to 0.511	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A -0.16 hour	0.530 grams per liter Interval 0.499 to 0.564	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A -0.08 hour	0.562 grams per liter Interval 0.539 to 0.585	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A Predose	0.555 grams per liter Interval 0.538 to 0.571	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 0.16 hour	0.578 grams per liter Interval 0.558 to 0.599	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 0.3 hour	0.592 grams per liter Interval 0.574 to 0.611	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 0.5 hour	0.574 grams per liter Interval 0.552 to 0.598	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 1 hour	0.552 grams per liter Interval 0.525 to 0.581	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 1.5 hours	0.557 grams per liter Interval 0.533 to 0.583	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 2 hours	0.568 grams per liter Interval 0.544 to 0.593	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 2.5 hours	0.574 grams per liter Interval 0.547 to 0.601	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 3 hours	0.572 grams per liter Interval 0.544 to 0.602	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 3.5 hours	0.574 grams per liter Interval 0.556 to 0.593	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 4 hours	0.593 grams per liter Interval 0.575 to 0.612	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 4.5 hours	0.603 grams per liter Interval 0.583 to 0.624	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 5 hours	0.590 grams per liter Interval 0.575 to 0.605	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 6 hours	0.356 grams per liter Interval 0.322 to 0.394	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 7 hours	0.172 grams per liter Interval 0.139 to 0.213	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A 8 hours	0.105 grams per liter Interval 0.073 to 0.151	—	—	—	—	—

SECONDARY outcome

Timeframe: -0.4, -0.3, -0.2, -0.16, -0.08, Predose, 0.16, 0.3, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7 and 8 hours postdose on Day 5 of Period 4 or Day 7 of Period 5

Population: PKS included all study participants that received at least one dose of active study drug and have at least one observable pharmacokinetic measurement. Here, n (number analyzed) signifies participants evaluable at specified time points only.

Continuous infusion of ethanol began with a 30 minute loading phase (prior to 0 hours) and was continued for 5 hours with adjustments during the infusion. Participants received either ethanol on Day 5 of Period 4 or Day 7 of Period 5. Therefore, the results were summarized by treatment.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=21 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A -0.4 hour	0.321 grams per liter Interval 0.281 to 0.367	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A -0.3 hour	0.464 grams per liter Interval 0.417 to 0.516	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A -0.2 hour	0.499 grams per liter Interval 0.451 to 0.553	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A -0.16 hour	0.524 grams per liter Interval 0.492 to 0.558	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A -0.08 hour	0.505 grams per liter Interval 0.468 to 0.545	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A Predose	0.499 grams per liter Interval 0.467 to 0.533	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 0.16 hour	0.591 grams per liter Interval 0.567 to 0.617	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 0.3 hour	0.622 grams per liter Interval 0.606 to 0.639	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 0.5 hour	0.608 grams per liter Interval 0.591 to 0.624	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 1 hour	0.581 grams per liter Interval 0.56 to 0.603	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 1.5 hours	0.566 grams per liter Interval 0.544 to 0.588	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 2 hours	0.566 grams per liter Interval 0.54 to 0.593	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 2.5 hours	0.579 grams per liter Interval 0.55 to 0.608	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 3 hours	0.608 grams per liter Interval 0.585 to 0.631	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 3.5 hours	0.602 grams per liter Interval 0.582 to 0.623	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 4 hours	0.612 grams per liter Interval 0.593 to 0.632	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 4.5 hours	0.610 grams per liter Interval 0.59 to 0.631	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 5 hours	0.613 grams per liter Interval 0.59 to 0.637	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 6 hours	0.373 grams per liter Interval 0.338 to 0.411	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 7 hours	0.199 grams per liter Interval 0.171 to 0.232	—	—	—	—	—
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A 8 hours	0.084 grams per liter Interval 0.066 to 0.108	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose on Day 5

Population: PKS included all study participants that received at least one dose of active study drug and have at least one observable pharmacokinetic measurement. Here, Number of participants analyzed signifies participants who were evaluable for the assessment.

Cmax,ss is the maximum observed plasma concentration at steady state of padsevonil.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=20 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=21 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part A	832.9 nanograms per milliliter Interval 488.3 to 1421.0	1077 nanograms per milliliter Interval 778.6 to 1489.0	—	—	—	—

SECONDARY outcome

Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose on Day 5

AUC0-tau is the area under the curve over a dosing interval of padsevonil.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=20 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=20 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part A	3504 hours*nanogram per milliliter Interval 2010.0 to 6109.0	4289 hours*nanogram per milliliter Interval 2904.0 to 6335.0	—	—	—	—

SECONDARY outcome

Timeframe: Predose up to 12 hours postdose

t1/2 is the apparent terminal half-life of padsevonil.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose up to 12 hours postdose

Population: PKS included all study participants that received at least one dose of active study drug and have at least one observable pharmacokinetic measurement.

t1/2 is the apparent terminal half-life of CBD.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=16 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Half-life (t1/2) of Cannabidiol During Part B	NA hours Analysis of this outcome measure was not performed because the study was terminated. At that time, Part A had been completed, and 16 study participants had been treated with CBD in Treatment Period 1 of Part B.	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose up to 12 hours postdose

CLss/F is the apparent total body clearance at steady state following extravascular administration of padsevonil.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose up to 12 hours postdose

Population: PKS included all study participants that received at least one dose of active study drug and have at least one observable pharmacokinetic measurement.

CLss/F is the apparent total body clearance at steady state following extravascular administration of CBD.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=16 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Apparent Total Body Clearance at Steady State (CLss/F) of Cannabidiol During Part B	NA liter per hour Analysis of this outcome measure was not performed because the study was terminated. At that time, Part A had been completed, and 16 study participants had been treated with CBD in Treatment Period 1 of Part B.	—	—	—	—	—

SECONDARY outcome

Timeframe: Treatment Period 1: Screening, Day 1 and Day 2

Population: FAS consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation.

Smooth pursuit to assess eye movement coordination and attention to evaluate the ethanol effect. The average percentage of smooth pursuit for all stimulus frequencies was used as a parameter.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=16 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Percentage of Smooth Pursuit Eye Movements During Part B	NA percentage of eye movements Standard Deviation NA Analysis of this outcome measure was not performed because the study was terminated. At that time, Part A had been completed, and 16 study participants had been treated with CBD in Treatment Period 1 of Part B.	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2

Population: FAS consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation. Here, n (number analyzed) signifies participants evaluable at specified time points only.

Sixteen saccades were recorded with interstimulus intervals varying randomly. Average values of latency (reaction time), saccadic peak velocity of all correct saccades, and inaccuracy of all saccades were used as parameters. Participants received either ethanol or placebo on Day 1 of Period 1 or on Day 3 of Period 2. Therefore, the results were summarized by treatment.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=24 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=23 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A Predose	497.873 degrees per second Standard Deviation 36.988	502.917 degrees per second Standard Deviation 32.543	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A 0.5 hour	471.465 degrees per second Standard Deviation 37.890	502.427 degrees per second Standard Deviation 47.354	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A 1 hour	458.726 degrees per second Standard Deviation 34.284	488.761 degrees per second Standard Deviation 35.226	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A 2 hours	455.138 degrees per second Standard Deviation 34.045	484.243 degrees per second Standard Deviation 37.299	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A 3 hours	455.445 degrees per second Standard Deviation 43.890	479.852 degrees per second Standard Deviation 33.906	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A 4 hours	459.700 degrees per second Standard Deviation 54.621	468.029 degrees per second Standard Deviation 36.669	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A 5 hours	447.909 degrees per second Standard Deviation 29.508	484.778 degrees per second Standard Deviation 32.631	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A 6 hours	466.417 degrees per second Standard Deviation 37.985	479.150 degrees per second Standard Deviation 37.994	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A 8 hours	474.283 degrees per second Standard Deviation 33.625	486.883 degrees per second Standard Deviation 38.078	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A 10 hours	484.513 degrees per second Standard Deviation 33.232	489.495 degrees per second Standard Deviation 38.495	—	—	—	—

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 5 of Period 4 or Day 7 of Period 5

Population: FAS consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation. Here, n (number analyzed) signifies participants evaluable at specified time points only.

Sixteen saccades were recorded with interstimulus intervals varying randomly. Average values of latency (reaction time), saccadic peak velocity of all correct saccades, and inaccuracy of all saccades were used as parameters. Participants received either ethanol or placebo on Day 5 of Period 4 or Day 7 of Period 5. Therefore, the results were summarized by treatment.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=23 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=23 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A 6 hours	436.268 degrees per second Standard Deviation 55.152	470.576 degrees per second Standard Deviation 47.370	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A Predose	481.335 degrees per second Standard Deviation 40.894	466.509 degrees per second Standard Deviation 43.334	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A 0.5 hour	434.465 degrees per second Standard Deviation 48.160	454.980 degrees per second Standard Deviation 35.882	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A 1 hour	405.517 degrees per second Standard Deviation 50.706	427.505 degrees per second Standard Deviation 42.232	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A 2 hours	414.268 degrees per second Standard Deviation 61.752	418.748 degrees per second Standard Deviation 49.071	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A 3 hours	401.548 degrees per second Standard Deviation 46.004	423.543 degrees per second Standard Deviation 51.720	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A 4 hours	410.386 degrees per second Standard Deviation 47.324	442.152 degrees per second Standard Deviation 46.641	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A 5 hours	418.252 degrees per second Standard Deviation 41.277	450.319 degrees per second Standard Deviation 38.954	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A 8 hours	480.891 degrees per second Standard Deviation 41.106	467.162 degrees per second Standard Deviation 37.902	—	—	—	—
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A 10 hours	474.209 degrees per second Standard Deviation 41.119	466.933 degrees per second Standard Deviation 43.241	—	—	—	—

SECONDARY outcome

Timeframe: Treatment Period 1: Screening, Day 1 and Day 2

Population: FAS consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=16 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Saccadic Peak Velocity to Assess Sedation During Part B	NA degrees per second Standard Deviation NA Analysis of this outcome measure was not performed because the study was terminated. At that time, Part A had been completed, and 16 study participants had been treated with CBD in Treatment Period 1 of Part B.	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2

Population: FAS consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation. Here, n (number analyzed) signifies participants evaluable at specified time points only.

The adaptive tracking test was performed as originally described by Borland and Nicholson (Borland and Nicholson, 1984). Performance was scored after a fixed period of 3.5 minutes and reflected visuo-motor control and vigilance. The average performance scores were used in the analysis. Participants received either ethanol or placebo on Day 1 of Period 1 or on Day 3 of Period 2. Therefore, the results were summarized by treatment.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=24 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=23 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A Predose	32.3704 percentage of time correctly tracked Standard Deviation 5.5709	32.0037 percentage of time correctly tracked Standard Deviation 5.6751	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A 0.5 hour	29.0825 percentage of time correctly tracked Standard Deviation 4.8924	32.0770 percentage of time correctly tracked Standard Deviation 5.7220	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A 1 hour	28.7825 percentage of time correctly tracked Standard Deviation 5.0093	32.0530 percentage of time correctly tracked Standard Deviation 5.6913	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A 2 hours	27.6325 percentage of time correctly tracked Standard Deviation 4.6875	32.6526 percentage of time correctly tracked Standard Deviation 5.5194	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A 3 hours	26.5765 percentage of time correctly tracked Standard Deviation 5.9118	32.3087 percentage of time correctly tracked Standard Deviation 6.0354	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A 4 hours	26.4087 percentage of time correctly tracked Standard Deviation 6.5784	31.8835 percentage of time correctly tracked Standard Deviation 6.0274	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A 5 hours	27.9500 percentage of time correctly tracked Standard Deviation 5.1829	32.0752 percentage of time correctly tracked Standard Deviation 5.8386	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A 6 hours	28.9587 percentage of time correctly tracked Standard Deviation 5.6291	32.0757 percentage of time correctly tracked Standard Deviation 5.6722	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A 8 hours	31.0778 percentage of time correctly tracked Standard Deviation 5.7553	32.0300 percentage of time correctly tracked Standard Deviation 5.8507	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A 10 hours	32.5391 percentage of time correctly tracked Standard Deviation 5.2327	33.3322 percentage of time correctly tracked Standard Deviation 5.9769	—	—	—	—

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours on Day 5 of Period 4 or Day 7 of Period 5

The adaptive tracking test was performed as originally described by Borland and Nicholson (Borland and Nicholson, 1984). Performance was scored after a fixed period of 3.5 minutes and reflected visuo-motor control and vigilance. The average performance scores were used in the analysis. Participants received either ethanol or placebo on Day 5 of Period 4 or Day 7 of Period 5. Therefore, the results were summarized by treatment.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=23 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=22 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A 6 hours	26.3652 percentage of time correctly tracked Standard Deviation 6.5759	30.3214 percentage of time correctly tracked Standard Deviation 6.4549	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A Predose	30.5017 percentage of time correctly tracked Standard Deviation 7.0354	29.0691 percentage of time correctly tracked Standard Deviation 7.1405	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A 0.5 hour	23.3339 percentage of time correctly tracked Standard Deviation 6.4727	25.8650 percentage of time correctly tracked Standard Deviation 7.7624	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A 1 hour	19.4317 percentage of time correctly tracked Standard Deviation 7.5471	20.5714 percentage of time correctly tracked Standard Deviation 7.7253	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A 2 hours	17.1617 percentage of time correctly tracked Standard Deviation 6.8895	19.3395 percentage of time correctly tracked Standard Deviation 7.8659	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A 3 hours	18.4870 percentage of time correctly tracked Standard Deviation 6.9150	25.0859 percentage of time correctly tracked Standard Deviation 7.2415	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A 4 hours	18.8713 percentage of time correctly tracked Standard Deviation 7.9952	27.5827 percentage of time correctly tracked Standard Deviation 6.8106	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A 5 hours	20.4422 percentage of time correctly tracked Standard Deviation 8.3476	29.4377 percentage of time correctly tracked Standard Deviation 6.5829	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A 8 hours	30.3570 percentage of time correctly tracked Standard Deviation 6.3134	31.3282 percentage of time correctly tracked Standard Deviation 5.9957	—	—	—	—
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A 10 hours	30.6039 percentage of time correctly tracked Standard Deviation 6.5557	31.9223 percentage of time correctly tracked Standard Deviation 7.1749	—	—	—	—

SECONDARY outcome

Timeframe: Treatment Period 1: Screening, Day 1 and Day 2

Population: FAS consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=16 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance During Part B	NA percentage of time correctly tracked Standard Deviation NA Analysis of this outcome measure was not performed because the study was terminated. At that time, Part A had been completed, and 16 study participants had been treated with CBD in Treatment Period 1 of Part B.	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2

Population: FAS consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation. Here, n (number analyzed) signifies participants evaluable at specified time points only.

Body Sway test measured the study participant's body movements in a single direction. Body sway was measured by CHCR NeuroCart. Study participants were asked to stand erect and motionless with their eyes closed. The amplitude and direction of any Body Sway was recorded for 1 minute. Participants received either ethanol or placebo on Day 1 of Period 1 or on Day 3 of Period 2. Therefore, the results were summarized by treatment.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=24 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=23 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A Predose	234.258 millimeters Standard Deviation 131.198	219.348 millimeters Standard Deviation 123.362	—	—	—	—
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A 0.5 hour	390.671 millimeters Standard Deviation 293.387	238.083 millimeters Standard Deviation 108.227	—	—	—	—
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A 1 hour	379.246 millimeters Standard Deviation 226.889	235.613 millimeters Standard Deviation 115.707	—	—	—	—
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A 2 hours	410.292 millimeters Standard Deviation 307.000	258.348 millimeters Standard Deviation 133.061	—	—	—	—
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A 3 hours	392.813 millimeters Standard Deviation 300.259	251.109 millimeters Standard Deviation 141.894	—	—	—	—
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A 4 hours	410.500 millimeters Standard Deviation 277.375	241.361 millimeters Standard Deviation 123.019	—	—	—	—
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A 5 hours	380.043 millimeters Standard Deviation 238.041	240.322 millimeters Standard Deviation 131.546	—	—	—	—
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A 6 hours	298.445 millimeters Standard Deviation 177.888	285.191 millimeters Standard Deviation 193.643	—	—	—	—
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A 8 hours	254.830 millimeters Standard Deviation 134.773	252.930 millimeters Standard Deviation 166.126	—	—	—	—
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A 10 hours	244.057 millimeters Standard Deviation 146.336	239.283 millimeters Standard Deviation 138.579	—	—	—	—

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours on Day 5 of Period 4 or Day 7 of Period 5

Body Sway test measured the study participant's body movements in a single direction. Body sway was measured by CHCR NeuroCart. Study participants were asked to stand erect and motionless with their eyes closed. The amplitude and direction of any Body Sway was recorded for 1 minute. Participants received either ethanol or placebo on Day 5 of Period 4 or Day 7 of Period 5. Therefore, the results were summarized by treatment.

Outcome measures

Outcome measures
Measure	Part A: Ethanol (FAS) n=23 Participants Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the FAS.	Part A: Placebo (FAS) n=22 Participants Participants received matching placebo (for ethanol IV infusion) on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the Full Analysis Set (FAS).	Part A: Ethanol (SS) Participants received ethanol 0.6 g/L IV infusion on Day 1 during TP1 in Treatment Sequence A and B and on Day 1 during TP2 in Treatment Sequence C and D. Participants formed the SS.	Part A: PSL (SS) Participants received PSL 100 mg or 200 mg oral tablets BID on Day 1 to 4 during TP3 in Treatment Sequence A, B, C and D. Participants formed the SS.	Part A: PSL + Ethanol (SS) Participants received PSL 200 mg BID oral tablets + Ethanol IV infusion on Day 5 during TP4 in Treatment Sequence A and C and on Day 7 during TP5 in Treatment Sequence B and D. Participants formed the SS.	Part A: PSL + Placebo (SS) Participants received PSL oral tablets 100 mg or 200 mg + Placebo (for ethanol IV infusion) on Day 7 during TP5 in Treatment Sequence A and C and on Day 5 during TP4 in Treatment Sequence B and D. Participants formed the SS.
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A Predose	294.843 millimeters Standard Deviation 227.524	317.484 millimeters Standard Deviation 321.623	—	—	—	—
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A 0.5 hour	746.161 millimeters Standard Deviation 648.448	661.550 millimeters Standard Deviation 943.498	—	—	—	—
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A 1 hour	1091.639 millimeters Standard Deviation 965.116	863.255 millimeters Standard Deviation 986.913	—	—	—	—
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A 2 hours	1170.452 millimeters Standard Deviation 1118.424	712.391 millimeters Standard Deviation 646.223	—	—	—	—
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A 3 hours	924.800 millimeters Standard Deviation 873.486	499.077 millimeters Standard Deviation 353.668	—	—	—	—
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A 4 hours	903.100 millimeters Standard Deviation 888.205	406.586 millimeters Standard Deviation 279.517	—	—	—	—
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A 5 hours	666.987 millimeters Standard Deviation 735.498	353.905 millimeters Standard Deviation 277.036	—	—	—	—
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A 6 hours	489.261 millimeters Standard Deviation 431.766	335.400 millimeters Standard Deviation 256.120	—	—	—	—
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A 8 hours	314.713 millimeters Standard Deviation 242.121	277.614 millimeters Standard Deviation 189.464	—	—	—	—
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A 10 hours	274.696 millimeters Standard Deviation 180.248	247.100 millimeters Standard Deviation 137.795	—	—	—	—

SECONDARY outcome

Timeframe: Treatment Period 1: Screening, Day 1 and Day 2

Population: FAS consisted of all study participants that were randomized, received study medication, and had at least one valid post-baseline primary pharmacodynamic assessment observation.