A Study to Test the Safety, and Tolerability of Padsevonil in Healthy Male Japanese Study Participants

Study Overview
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Brief Summary
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The purpose of the study is to investigate the pharmacokinetics (PK) of padesevonil in CYP2C19 genotyped healthy male Japanese study participants.

Official Title
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An Open-Label, Parallel Group, Single-Center Study to Investigate the Pharmacokinetic, Safety, and Tolerability Profiles of Padsevonil in CYP2C19 Genotyped Healthy Male Japanese Study Participants

Conditions
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Healthy Japanese Participants

Intervention / Treatment
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* Drug: Padsevonil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The study participant must be 20 to 55 years of age inclusive, at the time of signing the informed consent The study participant is overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring The study participant is of Japanese descent as evidenced by appearance and verbal confirmation of familial heritage The study participant has a body weight ≥50 kg and body mass index within the range [18 to 30] kg/m^2 (inclusive) The study participant is male Exclusion Criteria: The study participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would 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 the Screening Visit The study participant has a 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 The study participant has a history of unexplained syncope or a family history of sudden death due to long QT syndrome The study 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 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 The study participant has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) >1.0 x upper limit of normal (ULN) The study participant has bilirubin >1.0 x ULN (isolated bilirubin >1.0 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 %) The study participant has current or chronic history of liver disease or known hepatic or biliary abnormalities The study participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline. The study participant has made a blood or plasma donation or has had a comparable blood loss (>450 mL) within the last 30 days prior to Screening. Blood donation during the study is not permitted

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Extensive metabolizers<br>Participants will receive assigned single and multiple doses of padsevonil. | Drug: Padsevonil<br>* Padsevonil will be administered in predefined dosages.<br>|
| Experimental: Intermediate metabolizers<br>Participants will receive assigned single and multiple doses of padsevonil. | Drug: Padsevonil<br>* Padsevonil will be administered in predefined dosages.<br>|
| Experimental: Poor metabolizers<br>Participants will receive assigned single and multiple doses of padsevonil. | Drug: Padsevonil<br>* Padsevonil will be administered in predefined dosages.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil | Cmax is the maximum plasma drug concentration of PSL observed from pharmacokinetic samples taken at predefined time points. | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | 
| Area Under the Curve From 0 to t (AUC(0-t)) of a Single Dose Padsevonil | AUC(0-t) is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | 
| Area Under the Curve From Time 0 to Infinity (AUC) of a Single Dose Padsevonil | AUC is the area under the plasma concentration-time curve from time zero to infinity. | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | 
| Terminal Half-life (t1/2) of a Single Dose Padsevonil | The t1/2 is the apparent terminal half-life. Geometric Means and Geometric Coefficient of Variations were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | 
| Time to Reach the Maximum Plasma Concentration (Tmax) of a Single Dose Padsevonil | The tmax is the time to reach maximum plasma concentration. | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | 
| Maximum Plasma Concentration (Cmax) of Padsevonil at Steady-state (ss) | Cmax, ss is the maximum plasma concentration of PSL observed from pharmacokinetic samples, taken at predefined time point at a steady-state. | Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose | 
| Area Under the Curve Over a Dosing Interval (AUCtau) of Multiple Doses Padsevonil | AUCtau is the area under the plasma concentration time curve over a dosing interval. | Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose | 
| Terminal Half-life (t1/2) of Multiple Doses Padsevonil | The t1/2 is the apparent terminal half-life. | Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose | 
| Time to Reach Maximum Concentration (Tmax) for Padsevonil at Steady-state (ss) | The tmax, ss is the time of observed maximum plasma concentration at a steady-state. | Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose | 
| Percentage of Participants With Treatment Emergent Adverse Events During the Study | An Adverse Event (AE) is 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. | From Baseline until the Safety Follow-up Visit (up to Day 21) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Padsevonil, CYP2C19, Healthy Japanese Participants, Pharmacokinetics