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

Phase 1

Completed

Conditions: Healthy Japanese Participants

Interventions: Drug: Padsevonil

Registration Number: NCT04075409

Lead Sponsor: UCB Biopharma S.P.R.L.

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 39

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Extensive metabolizers	Padsevonil	Participants will receive assigned single and multiple doses of padsevonil.
Intermediate metabolizers	Padsevonil	Participants will receive assigned single and multiple doses of padsevonil.
Poor metabolizers	Padsevonil	Participants will receive assigned single and multiple doses of padsevonil.

Primary Outcome Measures

Name	Time	Method
Area Under the Curve From 0 to t (AUC(0-t)) of a Single Dose Padsevonil	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)	AUC(0-t) is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.
Percentage of Participants With Treatment Emergent Adverse Events During the Study	From Baseline until the Safety Follow-up Visit (up to Day 21)	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.
Terminal Half-life (t1/2) of a Single Dose Padsevonil	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)	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).
Time to Reach the Maximum Plasma Concentration (Tmax) of a Single Dose Padsevonil	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)	The tmax is the time to reach maximum plasma concentration.
Area Under the Curve Over a Dosing Interval (AUCtau) of Multiple Doses Padsevonil	Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose	AUCtau is the area under the plasma concentration time curve over a dosing interval.
Time to Reach Maximum Concentration (Tmax) for Padsevonil at Steady-state (ss)	Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose	The tmax, ss is the time of observed maximum plasma concentration at a steady-state.
Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil	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)	Cmax is the maximum plasma drug concentration of PSL observed from pharmacokinetic samples taken at predefined time points.
Area Under the Curve From Time 0 to Infinity (AUC) of a Single Dose Padsevonil	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)	AUC is the area under the plasma concentration-time curve from time zero to infinity.
Maximum Plasma Concentration (Cmax) of Padsevonil at Steady-state (ss)	Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose	Cmax, ss is the maximum plasma concentration of PSL observed from pharmacokinetic samples, taken at predefined time point at a steady-state.
Terminal Half-life (t1/2) of Multiple Doses Padsevonil	Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose	The t1/2 is the apparent terminal half-life.