A Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal or Moderately Impaired Hepatic Function

• Sponsor: UCB Biopharma S.P.R.L. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04136444
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Actual Duration (Months): 6.8
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the plasma pharmacokinetic (PK), safety and tolerability of padsevonil (PSL) in hepatically impaired and non-hepatically impaired study participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy Study Participants; Impaired Hepatic Function	Drug: Padsevonil	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Open-Label, Parallel-Group, Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal Hepatic Function or With Moderately Impaired Hepatic Function (Child-Pugh Class B)
• Actual Study Start Date: Oct 28, 2019
• Actual Primary Completion Date: May 22, 2020
• Actual Study Completion Date: May 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healthy participants Participants will receive assigned single and multiple doses of padsevonil.	Drug: Padsevonil; Padsevonil will be administered in predefined dosages.; Other Names: PSL UCB0942
Experimental: Hepatically impaired participants Participants will receive assigned single and multiple doses of padsevonil.	Drug: Padsevonil; Padsevonil will be administered in predefined dosages.; Other Names: PSL UCB0942

Outcome Measures

Primary Outcome Measures

1. 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, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose]

   Cmax is maximum observed plasma concentration.

2. Area Under the Plasma Concentration-time Curve From Time 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, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose]

   AUC (0-t) is defined as area under the plasma concentration-time curve from time zero to time t.

3. Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity 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, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose]

   AUC is defined as area under the plasma concentration-time curve from time 0 to infinity.

4. Maximum Observed Plasma Concentration at Steady-state (Cmax,ss) of Multiple Doses Padsevonil (PSL) [On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose]

   Cmax,ss is defined as maximum observed plasma concentration at steady-state.

5. Area Under the Concentration-time Curve (AUCtau) at Steady-state Over a Dosing Interval of Multiple Doses Padsevonil (PSL) [On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose]

   AUCtau is defined as area under the curve over a dosing interval at steady-state.

Secondary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [From Baseline until End of Study Visit (up to Day 18)]

   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. A treatment-emergent adverse event was characterized according to the intake of the study medication.

2. Number of Participants With Serious Adverse Events (SAEs) [From Baseline until End of Study Visit (up to Day 18)]

   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.

3. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study [From Baseline until End of Study Visit (up to Day 18)]

   An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event was characterized according to the intake of the study medication. TEAEs leading to discontinuation of the study are reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Participant must be male or female 18 to 70 years of age, inclusive, at the time of signing the informed consent

• Participant must have body weight of at least 50 kg (males) or 45 kg (females) and body mass index within the range 18 to 38 kg/m^2 (inclusive)

• Participants must meet the following requirements to be included in the study:

1. A male participant must agree to use contraception during both Treatment Periods and for at least 7 days after the last dose of study medication and refrain from donating sperm during this period

2. 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) OR A WOCBP who agrees to follow the contraceptive guidance during both Treatment Periods and for at least 90 days (or 5 terminal half-lives) after the final dose of study medication

Specific inclusion criteria for study participants WITH moderate hepatic insufficiency:

• Participant must have characteristics that will meet the clinical criteria usually found in participants with chronic hepatic insufficiency, as determined by medical history and physical examinations (eg, echography, scintigraphy, biopsy, or some specific laboratory values as evidence)

Exclusion Criteria:

• Participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or compromise the study participant's ability to participate in this study, such as 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 Visit

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

• Participant has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has had suicidal ideation in the past 6 months

• Participant has past or intended use of over-the-counter or prescription medication including herbal remedies and hepatic enzyme inhibitors within 2 weeks or 5 half-lives prior to dosing, particularly for participants with hepatic impairment where t1/2 may be prolonged. Specific medications may be allowed. Participant has used hepatic enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, phenytoin, isoniazid, or rifampicin, etc.) within 2 months prior to dosing unless required to treat an adverse event (AE). This does not include oral contraceptives not exceeding 30 μg ethinyl estradiol or postmenopausal hormone replacement therapy (HRT) or implants, patches, or intrauterine devices (IUDs) /intrauterine systems (IUSs) delivering progesterone (for female study participants) or acetaminophen with a maximal dose of 2 g/day or with a maximum of 10g over 15 days. In case of uncertainty, the UCB Study Physician should be consulted

• Participant has a history of chronic alcohol or drug abuse within the previous 12 months. Participant has a positive pre-study drug/alcohol screen (to include at minimum: amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines). A participant with a positive finding on the drug screen may still be enrolled at the discretion of the Investigator if a plausible clinical explanation exists (eg, prior or concomitant medication use)

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

• Participant has renal impairment as indicated by an estimated glomerular filtration rate (GFR) <60 mL/min, calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

• Participant tests positive for human immunodeficiency virus-1/2 antibody (HIV-1/2Ab) at Screening or within 3 months prior to the first dose of study medication

Specific exclusion criteria for study participants WITHOUT hepatic insufficiency

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

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

• 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) Note: For participants with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, a baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic Case Report Form (eCRF). If participant has >ULN ALT, AST, or ALP that does not meet the exclusion limit at Screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the study participant must be discussed with the UCB Study Physician

Specific exclusion criteria for study participants WITH moderate hepatic insufficiency

• Participant has acute liver failure of any etiology

• Participant has biliary cirrhosis

• Participant has used any drug indicated for the medical care of moderate hepatic insufficiency that is not established in dose and schedule for at least 14 days before the first liver function test (except paracetamol with a maximal dose of 2 g/day or with a maximum of 10 g over 15 days)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Up0056 004	Orlando	Florida	United States	32809

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 - Jul 2, 2019
• Statistical Analysis Plan - Nov 26, 2019

More Information

Publications

None provided.

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT04136444
• Other Study ID Numbers: UP0056
• First Posted: Oct 23, 2019
• Last Update Posted: Jul 28, 2021
• Last Verified: Jul 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
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by UCB Biopharma S.P.R.L.: Padsevonil; Phase 1; Pharmacokinetic; PSL

Study Results

Participant Flow

Recruitment Details	The study started to enroll study participants in October 2019 and concluded in May 2020.
Pre-assignment Detail	Participant Flow refers to the Safety Set (SS).

Arm/Group Title	Cohort A	Cohort B
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 milligrams (mg) on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg twice daily (bid) from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period 1 and 2.	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period 1 and 2.
Period Title: Overall Study
STARTED	3	9
COMPLETED	3	8
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Cohort A	Cohort B	Total Title
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 milligrams (mg) on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg twice daily (bid) from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period 1 and 2.	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period 1 and 2.
Overall Participants	3	9	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	9 100%	12 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.0 (7.5)	57.8 (4.3)	57.6 (4.9)
Sex: Female, Male (Count of Participants)
Female	2 66.7%	3 33.3%	5 41.7%
Male	1 33.3%	6 66.7%	7 58.3%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	0 0%	2 22.2%	2 16.7%
White	3 100%	7 77.8%	10 83.3%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL)
Description	Cmax is maximum observed plasma concentration.
Time Frame	Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set (PKS) is a subset of the Full Analysis Set (FAS), consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.

Arm/Group Title	Cohort A (PKS)	Cohort B (PKS)
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the Pharmacokinetic Set (PKS).	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period. Participants formed the PKS.
Measure Participants	3	8
Geometric Mean (95% Confidence Interval) [nanograms/milliliter (ng/mL)]	NA	531.4

2. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL)
Description	AUC (0-t) is defined as area under the plasma concentration-time curve from time zero to time t.
Time Frame	Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set (PKS) is a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.

Arm/Group Title	Cohort A (PKS)	Cohort B (PKS)
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the Pharmacokinetic Set (PKS).	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period. Participants formed the PKS.
Measure Participants	3	8
Geometric Mean (95% Confidence Interval) [hours*nanograms per milliliter (h*ng/mL)]	NA	3793

3. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity of a Single Dose Padsevonil (PSL)
Description	AUC is defined as area under the plasma concentration-time curve from time 0 to infinity.
Time Frame	Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set (PKS) is a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.

Arm/Group Title	Cohort A (PKS)	Cohort B (PKS)
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the Pharmacokinetic Set (PKS).	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period. Participants formed the PKS.
Measure Participants	3	8
Geometric Mean (95% Confidence Interval) [hours*ng/mL]	NA	3830

4. Primary Outcome

Title	Maximum Observed Plasma Concentration at Steady-state (Cmax,ss) of Multiple Doses Padsevonil (PSL)
Description	Cmax,ss is defined as maximum observed plasma concentration at steady-state.
Time Frame	On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set (PKS) is a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.

Arm/Group Title	Cohort A (PKS)	Cohort B (PKS)
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the Pharmacokinetic Set (PKS).	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period. Participants formed the PKS.
Measure Participants	3	8
Geometric Mean (95% Confidence Interval) [nanograms per milliliter (ng/mL)]	NA	558.1

5. Primary Outcome

Title	Area Under the Concentration-time Curve (AUCtau) at Steady-state Over a Dosing Interval of Multiple Doses Padsevonil (PSL)
Description	AUCtau is defined as area under the curve over a dosing interval at steady-state.
Time Frame	On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set (PKS) is a subset of the FAS, consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.

Arm/Group Title	Cohort A (PKS)	Cohort B (PKS)
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the Pharmacokinetic Set (PKS).	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 and multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. There was a Washout Period of 6 days between Treatment Period. Participants formed the PKS.
Measure Participants	3	8
Geometric Mean (95% Confidence Interval) [hours*ng/mL]	NA	3783

6. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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. A treatment-emergent adverse event was characterized according to the intake of the study medication.
Time Frame	From Baseline until End of Study Visit (up to Day 18)

Outcome Measure Data

Analysis Population Description

The Safety Set (SS) consisted of all study participants who received at least 1 dose of the investigational medicinal product (IMP). Study participants were classified according to the treatment that was actually received. All safety analyses were performed using the SS.

Arm/Group Title	Cohort A Single Dose (SS)	Cohort B Single Dose (SS)	Cohort A Multiple Dose (SS)	Cohort B Multiple Dose (SS)
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 as oral tablets. Participants formed the Safety Set (SS).	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 as oral tablets. Participants formed the SS.	Healthy study participants in Cohort A received multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the SS.	Participants with moderate hepatic insufficiency in Cohort B received multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the SS.
Measure Participants	3	9	3	9
Count of Participants [Participants]	3 100%	6 66.7%	3 25%	7 NaN

7. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs)
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 Study Visit (up to Day 18)

Outcome Measure Data

Analysis Population Description

The Safety Set (SS) consisted of all study participants who received at least 1 dose of the investigational medicinal product (IMP). Study participants were classified according to the treatment that was actually received. All safety analyses were performed using the SS.

Arm/Group Title	Cohort A Single Dose (SS)	Cohort B Single Dose (SS)	Cohort A Multiple Dose (SS)	Cohort B Multiple Dose (SS)
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 as oral tablets. Participants formed the Safety Set (SS).	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 as oral tablets. Participants formed the SS.	Healthy study participants in Cohort A received multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the SS.	Participants with moderate hepatic insufficiency in Cohort B received multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the SS.
Measure Participants	3	9	3	9
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN

8. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) 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 that does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event was characterized according to the intake of the study medication. TEAEs leading to discontinuation of the study are reported.
Time Frame	From Baseline until End of Study Visit (up to Day 18)

Outcome Measure Data

Analysis Population Description

The Safety Set (SS) consisted of all study participants who received at least 1 dose of the investigational medicinal product (IMP). Study participants were classified according to the treatment that was actually received. All safety analyses were performed using the SS.

Arm/Group Title	Cohort A Single Dose (SS)	Cohort B Single Dose (SS)	Cohort A Multiple Dose (SS)	Cohort B Multiple Dose (SS)
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 as oral tablets. Participants formed the Safety Set (SS).	Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 as oral tablets. Participants formed the SS.	Healthy study participants in Cohort A received multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the SS.	Participants with moderate hepatic insufficiency in Cohort B received multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the SS.
Measure Participants	3	9	3	9
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN

Adverse Events

Time Frame	Treatment-emergent Adverse Events (AEs) were collected from Baseline until End of Study Visit (up to Day 18)
Adverse Event Reporting Description	Treatment-emergent AE was defined as any AE with a start date/time on or after the first dose of study medication or any unresolved event already present before administration of study medication that worsened in intensity following exposure to the treatment.
Arm/Group Title	Cohort A Single Dose (SS)		Cohort B Single Dose (SS)		Cohort A Multiple Dose (SS)		Cohort B Multiple Dose (SS)
Arm/Group Description	Healthy study participants in Cohort A received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 as oral tablets. Participants formed the Safety Set (SS).		Participants with moderate hepatic insufficiency in Cohort B received a single dose of padsevonil 100 mg on Day 1 of Treatment Period 1 as oral tablets. Participants formed the SS.		Healthy study participants in Cohort A received multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the SS.		Participants with moderate hepatic insufficiency in Cohort B received multiple doses of padsevonil 100 mg bid from Day 8 to 11 and a single dose of padsevonil 100 mg on Day 12 during Treatment Period 2 as oral tablets. Participants formed the SS.
All Cause Mortality
	Cohort A Single Dose (SS)		Cohort B Single Dose (SS)		Cohort A Multiple Dose (SS)		Cohort B Multiple Dose (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/9 (0%)		0/3 (0%)		0/9 (0%)
Serious Adverse Events
	Cohort A Single Dose (SS)		Cohort B Single Dose (SS)		Cohort A Multiple Dose (SS)		Cohort B Multiple Dose (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/9 (0%)		0/3 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Cohort A Single Dose (SS)		Cohort B Single Dose (SS)		Cohort A Multiple Dose (SS)		Cohort B Multiple Dose (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		6/9 (66.7%)		3/3 (100%)		7/9 (77.8%)
Gastrointestinal disorders
Constipation	0/3 (0%)	0	0/9 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Gastrooesophageal reflux disease	0/3 (0%)	0	1/9 (11.1%)	1	0/3 (0%)	0	0/9 (0%)	0
Vomiting	0/3 (0%)	0	1/9 (11.1%)	1	0/3 (0%)	0	0/9 (0%)	0
General disorders
Fatigue	0/3 (0%)	0	4/9 (44.4%)	4	0/3 (0%)	0	1/9 (11.1%)	1
Gait disturbance	0/3 (0%)	0	2/9 (22.2%)	2	0/3 (0%)	0	0/9 (0%)	0
Nervous system disorders
Clumsiness	0/3 (0%)	0	1/9 (11.1%)	1	0/3 (0%)	0	0/9 (0%)	0
Headache	0/3 (0%)	0	0/9 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Somnolence	3/3 (100%)	3	2/9 (22.2%)	2	3/3 (100%)	3	3/9 (33.3%)	3
Psychiatric disorders
Bradyphrenia	0/3 (0%)	0	0/9 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Insomnia	0/3 (0%)	0	0/9 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)	0	0/9 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

More Information

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.