A Study to Test the Safety and Tolerability of Single and Multiple Doses of Padsevonil in Adult and Elderly Study Participants

• Sponsor: UCB Biopharma S.P.R.L. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04013191
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.8
• Patients Per Site Per Month: 9.9

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the plasma pharmacokinetic of padsevonil in adult and elderly study participants.

Condition or Disease	Intervention/Treatment	Phase
Elderly Study Participants; Adult Study Participants	Drug: Padsevonil	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Open-Label, Parallel-Group, Pharmacokinetic, Safety and Tolerability Study of Single and Multiple Oral Administrations of Padsevonil in Adult and Elderly Study Participants
• Actual Study Start Date: Jul 9, 2019
• Actual Primary Completion Date: Oct 3, 2019
• Actual Study Completion Date: Oct 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adult study participants Participants will receive assigned single and multiple doses of padsevonil.	Drug: Padsevonil; Padsevonil will be administered in predefined dosages.
Experimental: Elderly study participants Participants will receive assigned single and multiple doses of padsevonil.	Drug: Padsevonil; Padsevonil will be administered in predefined dosages.

Outcome Measures

Primary Outcome Measures

1. The Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL) [Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose]

   Cmax was measured in nanograms per milliliter (ng/mL).

2. The Area Under the Curve From 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL) [Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose]

   AUC0-t: area under the plasma concentration-time curve from time 0 to the last quantifiable concentration. It was measured in hours times nanograms per milliliter (h*ng/mL).

3. The Area Under the Curve (AUC) of a Single Dose Padsevonil (PSL) [Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose]

   AUC was measured in hours times nanograms per milliliter (h*ng/mL).

4. The Maximum Plasma Concentration at Steady-state (Cmax, ss) of Multiple Doses Padsevonil (PSL) [Plasma samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 12 hours on Day 13]

   Cmax, ss was measured in nanograms per milliliter (ng/mL).

5. The Area Under the Curve (AUCtau) Over a Dosing Interval of Multiple Doses Padsevonil (PSL) [Plasma samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 12 hours on Day 13]

   AUCtau was measured in hours times nanograms per milliliter (h*ng/mL).

Secondary Outcome Measures

1. The Amount of Padsevonil (PSL) Excreted in Urine [Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13]

   Samples were taken to assess the amount of padsevonil that was excreted in urine. Ae,ss refers to cumulative amount of PSL excreted in the urine at steady state.

2. The Ratio of Padsevonil (PSL) to Its Metabolites Excreted in Urine [Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13]

   Samples were taken to assess the metabolic ratio of padsevonil that was excreted in urine. MRAe was defined as the metabolic ratio of PSL to its metabolites for cumulative amount of PSL metabolites excreted in the urine. ss refers to steady state.

3. Number of Participants With Treatment-emergent Adverse Events [From Baseline until End-of-Treatment visit (up to Day 22)]

   An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.

4. Number of Participants With Serious Adverse Events [From Baseline until End-of-Treatment visit (up to Day 22)]

   A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires 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 patients, or may require medical or surgical intervention to prevent any of the above

5. Number of Participants With Treatment-emergent Adverse Events Leading to Discontinuation of the Study [From Baseline until End-of-Treatment visit (up to Day 22)]

   An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Study participants in the adult cohort must be ≥18 to 64 years of age at the time of signing the informed consent form (ICF)

• Study participants in the elderly cohort must be ≥65 years of age at the time of signing the ICF

• Study participants who are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring. In addition, elderly study participants must be considered to be in general good physical and mental health

• Study participants must have a body weight of at least 50 kg for males and 45 kg for females, and a body mass index within the range of 18 to 32 kg/m2 (inclusive)

Exclusion Criteria:

• Study participant has a current or past psychiatric condition that, in the opinion of the Investigator, could compromise the study participant's safety or ability to participate in this study, or a history of schizophrenia or other psychotic disorder, bipolar disorder, or severe unipolar depression. The presence of potential psychiatric exclusion criteria will be determined based on the psychiatric history collected at Screening

• Study 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

• Study participant has a known hypersensitivity to any components of the study medication as stated in this protocol

• Subject has a history of unexplained syncope or a family history of sudden death due to long QT syndrome

• Study participant has abnormal blood pressure

• Study participant has had 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

• Study participant has a lifetime history of suicide attempt, or has had suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the "Screening/Baseline" version of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening

• Study 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

• The study participant has used hepatic enzyme-inducing drugs within 2 months prior to dosing

• Study participant has previously received padsevonil (PSL) in this or another study

• Study participant has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) >1.0x upper limit of normal (ULN)

• Study participant has bilirubin >1.0xULN (isolated bilirubin >1.0xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

• Study 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)

• Study participant has any clinically relevant electrocardiogram (ECG) finding at Screening or at Baseline. Study participant has an abnormality in the 12-lead ECG that, in the opinion of the Investigator, increases the risks associated with participating in the study. In addition, any study participant with any of the following findings will be excluded: (a) QT interval corrected for heart rate using Bazett's formula (QTcB) or Fridericia's formula (QTcF) >450 ms in study participants in 2 of 3 ECG recordings; (b) other conduction abnormalities (defined as PR interval ≥220 ms); (c) irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular or rare ventricular ectopic beats. In case of an out of range result, 1 repeat will be allowed. If out of range again, the study participant cannot be included

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Up0053 001	San Antonio	Texas	United States	78209

Sponsors and Collaborators

• UCB Biopharma S.P.R.L.

Investigators

• Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study Documents (Full-Text)

• Study Protocol - May 29, 2019
• Statistical Analysis Plan - Sep 18, 2019

More Information

Publications

None provided.

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT04013191
• Other Study ID Numbers: UP0053
• First Posted: Jul 9, 2019
• Last Update Posted: Jun 30, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by UCB Biopharma S.P.R.L.: Padsevonil; Phase 1; Pharmacokinetic

Study Results

Participant Flow

Recruitment Details	The study started to enroll patients in July 2019 and concluded in October 2019.
Pre-assignment Detail	The study included a 28 days Screening period, a 21 days Treatment period: Period 1A single dose (SD) on Days 1 to 7 and Period 1B multiple dose (MD) on Days 8 to 21 and a Safety Follow-up period on Day 22. Participant Flow refers to the Full Analysis Set.

Arm/Group Title	Adults (18-64 Years)	Elderly (>= 65 Years)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil.	Participants received assigned single and multiple doses of padsevonil.
Period Title: Overall Study
STARTED	10	18
Completed Period 1A (Single Dose)	10	18
Completed Period 1B (Multiple Dose)	9	18
COMPLETED	9	18
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Adults (18-64 Years)	Elderly (>= 65 Years)	Total Title
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil.	Participants received assigned single and multiple doses of padsevonil.
Overall Participants	10	18	28
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	0 0%	10 35.7%
>=65 years	0 0%	18 100%	18 64.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.4 (10.2)	69.7 (4.5)	60.6 (14.1)
Sex: Female, Male (Count of Participants)
Female	6 60%	9 50%	15 53.6%
Male	4 40%	9 50%	13 46.4%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	1 10%	0 0%	1 3.6%
White	9 90%	18 100%	27 96.4%

Outcome Measures

1. Primary Outcome

Title	The Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL)
Description	Cmax was measured in nanograms per milliliter (ng/mL).
Time Frame	Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic-Per Protocol Set (PK-PPS) was a subset of the FAS, consisting of study participants who had no important protocol deviation (IPD) affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.

Arm/Group Title	Adults (18-64 Years) (PK-PPS)	Elderly (>= 65 Years) (PK-PPS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Measure Participants	10	18
Least Squares Mean (95% Confidence Interval) [ng/mL]	903.6	838.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adults (18-64 Years) (PK-PPS), Elderly (>= 65 Years) (PK-PPS)
	Comments	The analysis of variance (ANOVA) model included the fixed effects of age group. The natural logs were taken of the dependent variables and back-transformed after the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	0.928
	Confidence Interval	(2-Sided) 90%; 0.725 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	The Area Under the Curve From 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL)
Description	AUC0-t: area under the plasma concentration-time curve from time 0 to the last quantifiable concentration. It was measured in hours times nanograms per milliliter (h*ng/mL).
Time Frame	Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic-Per Protocol Set (PK-PPS) was a subset of the FAS, consisting of study participants who had no important protocol deviation (IPD) affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.

Arm/Group Title	Adults (18-64 Years) (PK-PPS)	Elderly (>= 65 Years) (PK-PPS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Measure Participants	10	18
Least Squares Mean (95% Confidence Interval) [h*ng/mL]	4915	6011

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adults (18-64 Years) (PK-PPS), Elderly (>= 65 Years) (PK-PPS)
	Comments	The ANOVA model included the fixed effects of age group. The natural logs were taken of the dependent variables and back-transformed after the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 90%; 0.894 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	The Area Under the Curve (AUC) of a Single Dose Padsevonil (PSL)
Description	AUC was measured in hours times nanograms per milliliter (h*ng/mL).
Time Frame	Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic-Per Protocol Set (PK-PPS) was a subset of the FAS, consisting of study participants who had no important protocol deviation (IPD) affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.

Arm/Group Title	Adults (18-64 Years) (PK-PPS)	Elderly (>= 65 Years) (PK-PPS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Measure Participants	10	18
Least Squares Mean (95% Confidence Interval) [h*ng/mL]	4950	6061

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adults (18-64 Years) (PK-PPS), Elderly (>= 65 Years) (PK-PPS)
	Comments	The ANOVA model included the fixed effects of age group. The natural logs were taken of the dependent variables and back-transformed after the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 90%; 0.893 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	The Maximum Plasma Concentration at Steady-state (Cmax, ss) of Multiple Doses Padsevonil (PSL)
Description	Cmax, ss was measured in nanograms per milliliter (ng/mL).
Time Frame	Plasma samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 12 hours on Day 13

Outcome Measure Data

Analysis Population Description

The PK-PPS was a subset of the FAS, consisting of study participants who had no IPD affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. 1 participant in the adult cohort discontinued due to a treatment emergent adverse event (TEAE) after 5 days of PSL administration in the MD Period.

Arm/Group Title	Adults (18-64 Years) (PK-PPS)	Elderly (>= 65 Years) (PK-PPS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Measure Participants	9	18
Least Squares Mean (95% Confidence Interval) [ng/mL]	1157	1180

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adults (18-64 Years) (PK-PPS), Elderly (>= 65 Years) (PK-PPS)
	Comments	The ANOVA model included the fixed effects of age group. The natural logs were taken of the dependent variables and back-transformed after the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 90%; 0.829 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	The Area Under the Curve (AUCtau) Over a Dosing Interval of Multiple Doses Padsevonil (PSL)
Description	AUCtau was measured in hours times nanograms per milliliter (h*ng/mL).
Time Frame	Plasma samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 12 hours on Day 13

Outcome Measure Data

Analysis Population Description

The PK-PPS was a subset of the FAS, consisting of study participants who had no IPD affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. 1 participant in the adult cohort discontinued due to a TEAE after 5 days of PSL administration in the MD Period.

Arm/Group Title	Adults (18-64 Years) (PK-PPS)	Elderly (>= 65 Years) (PK-PPS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Measure Participants	9	18
Least Squares Mean (95% Confidence Interval) [h*ng/mL]	5346	6307

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adults (18-64 Years) (PK-PPS), Elderly (>= 65 Years) (PK-PPS)
	Comments	The ANOVA model included the fixed effects of age group. The natural logs were taken of the dependent variables and back-transformed after the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point Estimate
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 90%; 0.908 to 1.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	The Amount of Padsevonil (PSL) Excreted in Urine
Description	Samples were taken to assess the amount of padsevonil that was excreted in urine. Ae,ss refers to cumulative amount of PSL excreted in the urine at steady state.
Time Frame	Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic-Per Protocol Set (PK-PPS) was a subset of the FAS, consisting of study participants who had no important protocol deviation (IPD) affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.

Arm/Group Title	Adults (18-64 Years) (PK-PPS)	Elderly (>= 65 Years) (PK-PPS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Measure Participants	10	18
Single dose: Day 1 (Ae)	0.0862 (153.9)	0.0979 (45.9)
Multiple dose: Day 13 (Ae,ss)	0.0924 (109.5)	0.166 (45.5)
Metabolite 1, Single dose: Day 1 (Ae)	0.941 (79.9)	1.13 (20.3)
Metabolite 1, Multiple dose: Day 13 (Ae,ss)	1.16 (96.9)	1.86 (35.9)
Metabolite 2, Single dose: Day 1 (Ae)	18.7 (68.3)	14.6 (54.2)
Metabolite 2, Multiple dose: Day 13 (Ae,ss)	13.3 (79.5)	14.4 (45.9)

7. Secondary Outcome

Title	The Ratio of Padsevonil (PSL) to Its Metabolites Excreted in Urine
Description	Samples were taken to assess the metabolic ratio of padsevonil that was excreted in urine. MRAe was defined as the metabolic ratio of PSL to its metabolites for cumulative amount of PSL metabolites excreted in the urine. ss refers to steady state.
Time Frame	Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic-Per Protocol Set (PK-PPS) was a subset of the FAS, consisting of study participants who had no important protocol deviation (IPD) affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.

Arm/Group Title	Adults (18-64 Years) (PK-PPS)	Elderly (>= 65 Years) (PK-PPS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Measure Participants	10	18
Metabolite 1, Single dose: Day 1 (MRAe)	10.6 (52.8)	11.2 (40.3)
Metabolite 1, Multiple dose: Day 13 (MRAe,ss)	12.2 (43.9)	10.9 (38.2)
Metabolite 2, Single dose: Day 1 (MRAe)	217 (122.3)	149 (81.8)
Metabolite 2, Multiple dose: Day 13 (MRAe,ss)	144 (81.1)	86.8 (67.7)

8. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events
Description	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.
Time Frame	From Baseline until End-of-Treatment visit (up to Day 22)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all study participants who signed the informed consent form (ICF) and received at least 1 dose of PSL.

Arm/Group Title	Adults (18-64 Years) (FAS)	Elderly (>= 65 Years) (FAS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Full Analysis Set (FAS).	Participants received assigned single and multiple doses of padsevonil, forming the FAS.
Measure Participants	10	18
Single Dose Period (1A)	10 100%	18 100%
Multiple Dose Period (1B)	10 100%	17 94.4%

9. Secondary Outcome

Title	Number of Participants With Serious Adverse Events
Description	A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires 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 patients, or may require medical or surgical intervention to prevent any of the above
Time Frame	From Baseline until End-of-Treatment visit (up to Day 22)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all study participants who signed the informed consent form (ICF) and received at least 1 dose of PSL.

Arm/Group Title	Adults (18-64 Years) (FAS)	Elderly (>= 65 Years) (FAS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Full Analysis Set (FAS).	Participants received assigned single and multiple doses of padsevonil, forming the FAS.
Measure Participants	10	18
Single Dose Period (1A)	0 0%	0 0%
Multiple Dose Period (1B)	0 0%	0 0%

10. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events Leading to Discontinuation of the Study
Description	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject 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.
Time Frame	From Baseline until End-of-Treatment visit (up to Day 22)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all study participants who signed the informed consent form (ICF) and received at least 1 dose of PSL.

Arm/Group Title	Adults (18-64 Years) (FAS)	Elderly (>= 65 Years) (FAS)
Arm/Group Description	Participants received assigned single and multiple doses of padsevonil, forming the Full Analysis Set (FAS).	Participants received assigned single and multiple doses of padsevonil, forming the FAS.
Measure Participants	10	18
Single Dose Period (1A)	0 0%	0 0%
Multiple Dose Period (1B)	1 10%	0 0%

Adverse Events

Time Frame	Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Arm/Group Title	Adults (18-64 Years) (FAS) SD Period (1A)		Elderly (>= 65 Years) (FAS) SD Period (1A)		Adults (18-64 Years) (FAS) MD Period (1B)		Elderly (>= 65 Years) (FAS) MD Period (1B)
Arm/Group Description	Participants received a single dose of padsevonil during Period (1A), forming the FAS.		Participants received a single dose of padsevonil during Period (1A), forming the FAS.		Participants received multiple doses of padsevonil during Period (1B), forming the FAS.		Participants received multiple doses of padsevonil during Period (1B), forming the FAS.
All Cause Mortality
	Adults (18-64 Years) (FAS) SD Period (1A)		Elderly (>= 65 Years) (FAS) SD Period (1A)		Adults (18-64 Years) (FAS) MD Period (1B)		Elderly (>= 65 Years) (FAS) MD Period (1B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/18 (0%)		0/10 (0%)		0/18 (0%)
Serious Adverse Events
	Adults (18-64 Years) (FAS) SD Period (1A)		Elderly (>= 65 Years) (FAS) SD Period (1A)		Adults (18-64 Years) (FAS) MD Period (1B)		Elderly (>= 65 Years) (FAS) MD Period (1B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/18 (0%)		0/10 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Adults (18-64 Years) (FAS) SD Period (1A)		Elderly (>= 65 Years) (FAS) SD Period (1A)		Adults (18-64 Years) (FAS) MD Period (1B)		Elderly (>= 65 Years) (FAS) MD Period (1B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		18/18 (100%)		10/10 (100%)		17/18 (94.4%)
Blood and lymphatic system disorders
Neutrophilia	0/10 (0%)	0	1/18 (5.6%)	1	0/10 (0%)	0	0/18 (0%)	0
Ear and labyrinth disorders
Vertigo	1/10 (10%)	1	0/18 (0%)	0	0/10 (0%)	0	0/18 (0%)	0
Eye disorders
Diplopia	0/10 (0%)	0	1/18 (5.6%)	1	0/10 (0%)	0	0/18 (0%)	0
Visual impairment	1/10 (10%)	1	0/18 (0%)	0	0/10 (0%)	0	0/18 (0%)	0
Vision blurred	0/10 (0%)	0	0/18 (0%)	0	0/10 (0%)	0	2/18 (11.1%)	2
Gastrointestinal disorders
Constipation	1/10 (10%)	1	2/18 (11.1%)	2	1/10 (10%)	1	1/18 (5.6%)	1
Nausea	2/10 (20%)	2	1/18 (5.6%)	1	2/10 (20%)	2	1/18 (5.6%)	1
Vomiting	1/10 (10%)	1	0/18 (0%)	0	0/10 (0%)	0	0/18 (0%)	0
Diarrhoea	0/10 (0%)	0	0/18 (0%)	0	0/10 (0%)	0	1/18 (5.6%)	1
Investigations
Blood pressure systolic decreased	1/10 (10%)	1	0/18 (0%)	0	2/10 (20%)	2	0/18 (0%)	0
White blood cell count increased	0/10 (0%)	0	1/18 (5.6%)	1	0/10 (0%)	0	0/18 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/10 (0%)	0	2/18 (11.1%)	2	0/10 (0%)	0	0/18 (0%)	0
Muscle spasms	0/10 (0%)	0	1/18 (5.6%)	1	0/10 (0%)	0	1/18 (5.6%)	1
Myalgia	0/10 (0%)	0	0/18 (0%)	0	0/10 (0%)	0	1/18 (5.6%)	1
Nervous system disorders
Somnolence	9/10 (90%)	9	17/18 (94.4%)	17	10/10 (100%)	10	16/18 (88.9%)	16
Dizziness	2/10 (20%)	2	5/18 (27.8%)	5	4/10 (40%)	4	6/18 (33.3%)	6
Headache	1/10 (10%)	1	1/18 (5.6%)	1	1/10 (10%)	1	4/18 (22.2%)	4
Cognitive disorder	0/10 (0%)	0	1/18 (5.6%)	1	0/10 (0%)	0	0/18 (0%)	0
Aphasia	0/10 (0%)	0	0/18 (0%)	0	0/10 (0%)	0	1/18 (5.6%)	1
Memory impairment	0/10 (0%)	0	0/18 (0%)	0	0/10 (0%)	0	1/18 (5.6%)	1
Psychiatric disorders
Sleep disorder	0/10 (0%)	0	1/18 (5.6%)	1	0/10 (0%)	0	0/18 (0%)	0
Disinhibition	0/10 (0%)	0	0/18 (0%)	0	1/10 (10%)	1	0/18 (0%)	0
Enuresis	0/10 (0%)	0	0/18 (0%)	0	0/10 (0%)	0	1/18 (5.6%)	1
Initial insomnia	0/10 (0%)	0	0/18 (0%)	0	0/10 (0%)	0	1/18 (5.6%)	1
Insomnia	0/10 (0%)	0	0/18 (0%)	0	1/10 (10%)	1	0/18 (0%)	0
Irritability	0/10 (0%)	0	0/18 (0%)	0	0/10 (0%)	0	1/18 (5.6%)	1
Mania	0/10 (0%)	0	0/18 (0%)	0	1/10 (10%)	1	0/18 (0%)	0
Skin and subcutaneous tissue disorders
Skin erosion	0/10 (0%)	0	1/18 (5.6%)	1	0/10 (0%)	0	0/18 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.