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

A Double-Blind, Placebo-Controlled, Randomized, Single-Center, Cross-Over Study to Investigate the Pharmacodynamic, Pharmacokinetic, Safety, and Tolerability Profiles of Padsevonil in Healthy Study Participants Receiving Either Ethanol or Cannabidiol

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04039919

Enrollment

Registered

2019-07-31

Start date

2019-07-17

Completion date

2020-05-22

Last updated

2021-06-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Participants

Keywords

Ethanol, Cannabidiol, Padsevonil

Brief summary

The purpose of the study is to evaluate the pharmacodynamic (PD) interaction between steady-steady treatment with padsevonil (PSL) and Ethanol and the pharmacokinetic (PK) interaction between stead-state treatment with PSL and cannabidiol (CBD).

Interventions

DRUGPadsevonil

Padsevonil will be administered in predefined dosages.

DRUGPlacebo (PSL)

Placebo will be provided matching Padsevonil to maintain the blinding.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring * Participant must have previous experience with alcohol consumption and, therefore, must be familiar with the effects and able to tolerate social amounts of alcohol * Participant has a body weight of at least 50 kg (males) or 45 kg (females) and body mass index (BMI) within the range 18 to 30 kg/m2 (inclusive) * Participants are male or female: * A male participant must agree to use contraception as detailed in the protocol during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: * Not a woman of childbearing potential (WOCBP) as defined n the protocol OR * A WOCBP who agrees to follow the contraceptive guidance in the protocol during the Treatment Period and for at least 90 days after the last dose of study treatment

Exclusion criteria

* Participant has history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data * Participant has a history of chronic alcohol or drug abuse within the previous 6 months or the presence of drug or alcohol dependency at Screening or Day -1 or tests positive for alcohol and/or drugs at Screening or Day -1 * Participant has a known hypersensitivity to any components of the study medication or comparative drugs (and/or an investigational device) as stated in this protocol * Participant has a history of unexplained syncope or a family history of sudden death due to long QT syndrome * Participant has lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years * Participant has past or intended use of over-the-counter or prescription medication including herbal medications within 2 weeks or 5 half-lives prior to dosing * Participant has used hepatic enzyme-inducing drugs within 2 months prior to dosing * Participant has alanine transaminase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) \>1.0x upper limit of normal (ULN) * Participant has current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) * Participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline * Participant has the presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to dosing * Participant has a positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention * Participant has a positive human immunodeficiency virus (HIV) antibody test

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	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	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.
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	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	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.
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part B	Predose up to 12 hours postdose	Cmax is maximum observed plasma concentration at steady state of padsevonil.
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Cannabidiol During Part B	Predose up to 12 hours postdose	Cmax is maximum observed plasma concentration at steady state of CBD.
Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part B	Predose up to 12 hours post dose	AUCtau is the area under the curve over a dosing interval of padsevonil.
Area Under the Curve Over a Dosing Interval (AUCtau) of Cannabidiol During Part B	Predose up to 12 hours postdose	AUCtau is the area under the curve over a dosing interval of CBD.

Secondary

Measure	Time frame	Description
Apparent Total Body Clearance at Steady State (CLss/F) of Padsevonil During Part B	Predose up to 12 hours postdose	CLss/F is the apparent total body clearance at steady state following extravascular administration of padsevonil.
Apparent Total Body Clearance at Steady State (CLss/F) of Cannabidiol During Part B	Predose up to 12 hours postdose	CLss/F is the apparent total body clearance at steady state following extravascular administration of CBD.
Percentage of Smooth Pursuit Eye Movements During Part B	Treatment Period 1: Screening, Day 1 and Day 2	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.
Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A	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	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.
Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A	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	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.
Saccadic Peak Velocity to Assess Sedation During Part B	Treatment Period 1: Screening, Day 1 and Day 2	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.
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, 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	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.
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, 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.
Adaptive Tracking to Assess Visuo-Motor Control and Vigilance During Part B	Treatment Period 1: Screening, Day 1 and Day 2	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.
Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	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	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.
Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A	-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	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.
Body Sway to Assess Postural Stability During Part B	Treatment Period 1: Screening, Day 1 and Day 2	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.
Number of Participants With Adverse Events During Part A	From Screening up to the Safety Follow-up visit of Part A (up to Day 26)	An adverse event (AE) was any untoward medical occurrence in a participant or trial participant that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.
Number of Participants With Adverse Events During Part B	From Screening up to the Safety Follow-up visit of Part B (up to Day 66)	An AE was any untoward medical occurrence in a participant or trial participant that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.
Number of Participants With Serious Adverse Events During Part A	From Screening up to the Safety Follow-up visit of Part A (up to Day 26)	A serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, is life-threatening, required in patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, is an infection that requires treatment parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the participants, or may require medical or surgical intervention to prevent any of the above.
Number of Participants With Serious Adverse Events During Part B	From Screening up to the Safety Follow-up visit of Part B (up to Day 66)	A SAE was any untoward medical occurrence that at any dose resulted in death, is life-threatening, required in patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, is an infection that requires treatment parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the participants, or may require medical or surgical intervention to prevent any of the above.
Number of Participants With Treatment-related Adverse Events During Part A	From Baseline up to Safety Follow-up visit of Part A (up to Day 26)	Treatment-related adverse event was an adverse event for which a causal relationship between the product and the occurrence is suspected.
Number of Participants With Treatment-related Adverse Events During Part B	From Baseline up to Safety Follow-up visit of Part B (up to Day 66)	Treatment-related adverse event was an adverse event for which a causal relationship between the product and the occurrence is suspected.
Number of Participants With Adverse Events Leading to Discontinuation of the Study During Part A	From Screening up to Safety Follow-up visit of Part A (up to Day 26)	An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Number of Participants With Adverse Events Leading to Discontinuation of the Study During Part B	From Screening up to Safety Follow-up visit of Part B (up to Day 66)	An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	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.
Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A	-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	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.
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part A	Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose on Day 5	Cmax,ss is the maximum observed plasma concentration at steady state of padsevonil.
Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part A	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.
Half-life (t1/2) of Padsevonil During Part B	Predose up to 12 hours postdose	t1/2 is the apparent terminal half-life of padsevonil.
Half-life (t1/2) of Cannabidiol During Part B	Predose up to 12 hours postdose	t1/2 is the apparent terminal half-life of CBD.

Countries

Netherlands

Participant flow

Recruitment details

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

Pre-assignment details

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

Participants by arm

Arm	Count
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.	7
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.	6
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.	5
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.	6
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.	16
Total Title	40
Total	80

Withdrawals & dropouts

Period	Reason	FG000	FG004
Treatment Period 1	Sponsor's decision	0	16
Treatment Period 1	Withdrawal by Subject	1	0
Treatment Period 5	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Part A: Treatment Sequence A	Part A: Treatment Sequence B	Part A: Treatment Sequence C	Part A: Treatment Sequence D	Part B: Cannabidiol (CBD)	Total Title
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	7 Participants	6 Participants	5 Participants	6 Participants	16 Participants	40 Participants
Age, Continuous	30.3 years STANDARD_DEVIATION 9.9	30.8 years STANDARD_DEVIATION 9.1	28.4 years STANDARD_DEVIATION 7	30.7 years STANDARD_DEVIATION 4.1	27.9 years STANDARD_DEVIATION 9.3	29.2 years STANDARD_DEVIATION 8.2
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Other or Mixed	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants	3 Participants
Race/Ethnicity, Customized White	7 Participants	5 Participants	5 Participants	4 Participants	15 Participants	36 Participants
Sex: Female, Male Female	1 Participants	4 Participants	1 Participants	1 Participants	11 Participants	18 Participants
Sex: Female, Male Male	6 Participants	2 Participants	4 Participants	5 Participants	5 Participants	22 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	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	0 / 24	0 / 23	0 / 24	0 / 23	0 / 23	0 / 23	0 / 16	0 / 16
other Total, other adverse events	4 / 24	4 / 23	17 / 24	22 / 23	22 / 23	18 / 23	2 / 16	11 / 16
serious Total, serious adverse events	0 / 24	0 / 23	0 / 24	0 / 23	0 / 23	0 / 23	0 / 16	0 / 16

Outcome results

Primary

Area Under the Curve Over a Dosing Interval (AUCtau) of Cannabidiol During Part B

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

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)
Part A: Ethanol (FAS)	Area Under the Curve Over a Dosing Interval (AUCtau) of Cannabidiol During Part B	NA hours*nanogram per milliliter

Primary

Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part B

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

Time frame: Predose up to 12 hours post dose

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.

Primary

Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Cannabidiol During Part B

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

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)
Part A: Ethanol (FAS)	Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Cannabidiol During Part B	NA nanograms per milliliter

Primary

Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part B

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

Time frame: Predose up to 12 hours postdose

Primary

Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A: Ethanol (FAS)	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 9.11
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	6 hours	43.300 percentage of eye movements	Standard Deviation 8.96
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	Predose	43.252 percentage of eye movements	Standard Deviation 8.688
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	4 hours	42.478 percentage of eye movements	Standard Deviation 9.351
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	0.5 hour	43.661 percentage of eye movements	Standard Deviation 9.345
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	10 hours	43.504 percentage of eye movements	Standard Deviation 11.394
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	1 hour	43.748 percentage of eye movements	Standard Deviation 10.298
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	5 hours	42.622 percentage of eye movements	Standard Deviation 9.2
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	2 hours	42.930 percentage of eye movements	Standard Deviation 9.636
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	8 hours	44.026 percentage of eye movements	Standard Deviation 10.085
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A	3 hours	42.809 percentage of eye movements	Standard Deviation 10.639

Primary

Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A: Ethanol (FAS)	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 9.93
Part A: Ethanol (FAS)	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 7.14
Part A: Ethanol (FAS)	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 6.79
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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 6.75
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	6 hours	38.945 percentage of eye movements	Standard Deviation 9.676
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	Predose	41.402 percentage of eye movements	Standard Deviation 8.5
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	4 hours	36.668 percentage of eye movements	Standard Deviation 8.411
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	0.5 hour	39.655 percentage of eye movements	Standard Deviation 9.703
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	10 hours	38.591 percentage of eye movements	Standard Deviation 9.508
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	1 hour	35.814 percentage of eye movements	Standard Deviation 7.893
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	5 hours	35.714 percentage of eye movements	Standard Deviation 8.865
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	2 hours	36.036 percentage of eye movements	Standard Deviation 9.172
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	8 hours	37.973 percentage of eye movements	Standard Deviation 8.849
Part A: Placebo (FAS)	Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A	3 hours	36.727 percentage of eye movements	Standard Deviation 9.512

Secondary

Adaptive Tracking to Assess Visuo-Motor Control and Vigilance During Part B

Time frame: 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.

Arm	Measure	Value (MEAN)
Part A: Ethanol (FAS)	Adaptive Tracking to Assess Visuo-Motor Control and Vigilance During Part B	NA percentage of time correctly tracked

Secondary

Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Placebo (FAS)	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	32.0757 percentage of time correctly tracked	Standard Deviation 5.6722
Part A: Placebo (FAS)	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	32.0037 percentage of time correctly tracked	Standard Deviation 5.6751
Part A: Placebo (FAS)	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	31.8835 percentage of time correctly tracked	Standard Deviation 6.0274
Part A: Placebo (FAS)	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	32.0770 percentage of time correctly tracked	Standard Deviation 5.722
Part A: Placebo (FAS)	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	33.3322 percentage of time correctly tracked	Standard Deviation 5.9769
Part A: Placebo (FAS)	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	32.0530 percentage of time correctly tracked	Standard Deviation 5.6913
Part A: Placebo (FAS)	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	32.0752 percentage of time correctly tracked	Standard Deviation 5.8386
Part A: Placebo (FAS)	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	32.6526 percentage of time correctly tracked	Standard Deviation 5.5194
Part A: Placebo (FAS)	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	32.0300 percentage of time correctly tracked	Standard Deviation 5.8507
Part A: Placebo (FAS)	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	32.3087 percentage of time correctly tracked	Standard Deviation 6.0354

Secondary

Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A

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.

Time frame: 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

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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 6.915
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Placebo (FAS)	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	30.3214 percentage of time correctly tracked	Standard Deviation 6.4549
Part A: Placebo (FAS)	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	29.0691 percentage of time correctly tracked	Standard Deviation 7.1405
Part A: Placebo (FAS)	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	27.5827 percentage of time correctly tracked	Standard Deviation 6.8106
Part A: Placebo (FAS)	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	25.8650 percentage of time correctly tracked	Standard Deviation 7.7624
Part A: Placebo (FAS)	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	31.9223 percentage of time correctly tracked	Standard Deviation 7.1749
Part A: Placebo (FAS)	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	20.5714 percentage of time correctly tracked	Standard Deviation 7.7253
Part A: Placebo (FAS)	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	29.4377 percentage of time correctly tracked	Standard Deviation 6.5829
Part A: Placebo (FAS)	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	19.3395 percentage of time correctly tracked	Standard Deviation 7.8659
Part A: Placebo (FAS)	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	31.3282 percentage of time correctly tracked	Standard Deviation 5.9957
Part A: Placebo (FAS)	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	25.0859 percentage of time correctly tracked	Standard Deviation 7.2415

Secondary

Apparent Total Body Clearance at Steady State (CLss/F) of Cannabidiol During Part B

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

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)
Part A: Ethanol (FAS)	Apparent Total Body Clearance at Steady State (CLss/F) of Cannabidiol During Part B	NA liter per hour

Secondary

Apparent Total Body Clearance at Steady State (CLss/F) of Padsevonil During Part B

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

Time frame: Predose up to 12 hours postdose

Secondary

Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part A

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

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)
Part A: Ethanol (FAS)	Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part A	3504 hours*nanogram per milliliter
Part A: Placebo (FAS)	Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part A	4289 hours*nanogram per milliliter

Comparison: The log-transformed PK parameters was analyzed by a mixed ANOVA with period and treatment as fixed effects and study participant as the random effect. The estimates and confidence intervals are back-transformed after the analysis.90% CI: [0.6999, 0.9942]

Secondary

Body Sway to Assess Postural Stability During Part B

Time frame: 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.

Arm	Measure	Value (MEAN)
Part A: Ethanol (FAS)	Body Sway to Assess Postural Stability During Part B	NA millimeters

Secondary

Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	6 hours	285.191 millimeters	Standard Deviation 193.643
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	Predose	219.348 millimeters	Standard Deviation 123.362
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	4 hours	241.361 millimeters	Standard Deviation 123.019
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	0.5 hour	238.083 millimeters	Standard Deviation 108.227
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	10 hours	239.283 millimeters	Standard Deviation 138.579
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	1 hour	235.613 millimeters	Standard Deviation 115.707
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	5 hours	240.322 millimeters	Standard Deviation 131.546
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	2 hours	258.348 millimeters	Standard Deviation 133.061
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	8 hours	252.930 millimeters	Standard Deviation 166.126
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A	3 hours	251.109 millimeters	Standard Deviation 141.894

Secondary

Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A

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.

Time frame: 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

Arm	Measure	Group	Value (MEAN)	Dispersion
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	6 hours	335.400 millimeters	Standard Deviation 256.12
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	Predose	317.484 millimeters	Standard Deviation 321.623
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	4 hours	406.586 millimeters	Standard Deviation 279.517
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	0.5 hour	661.550 millimeters	Standard Deviation 943.498
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	10 hours	247.100 millimeters	Standard Deviation 137.795
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	1 hour	863.255 millimeters	Standard Deviation 986.913
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	5 hours	353.905 millimeters	Standard Deviation 277.036
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	2 hours	712.391 millimeters	Standard Deviation 646.223
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	8 hours	277.614 millimeters	Standard Deviation 189.464
Part A: Placebo (FAS)	Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A	3 hours	499.077 millimeters	Standard Deviation 353.668

Secondary

Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A

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.

Time frame: -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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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

Secondary

Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A

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.

Time frame: -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.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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
Part A: Ethanol (FAS)	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

Secondary

Half-life (t1/2) of Cannabidiol During Part B

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

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)
Part A: Ethanol (FAS)	Half-life (t1/2) of Cannabidiol During Part B	NA hours

Secondary

Half-life (t1/2) of Padsevonil During Part B

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

Time frame: Predose up to 12 hours postdose

Secondary

Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part A

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

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

Arm	Measure	Value (GEOMETRIC_MEAN)
Part A: Ethanol (FAS)	Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part A	832.9 nanograms per milliliter
Part A: Placebo (FAS)	Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part A	1077 nanograms per milliliter

Comparison: The log-transformed PK parameters was analyzed by a mixed analysis of variance (ANOVA) with period and treatment as fixed effects and study participant as the random effect. The estimates and confidence intervals are back-transformed after the analysis.90% CI: [0.6513, 0.9461]

Secondary

Number of Participants With Adverse Events During Part A

An adverse event (AE) was any untoward medical occurrence in a participant or trial participant that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.

Time frame: From Screening up to the Safety Follow-up visit of Part A (up to Day 26)