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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Japanese Participants
• Intervention / Treatment: Drug: Padsevonil

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Up0083 001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: UCB Biopharma S.P.R.L.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): December 27, 2019
• Study Completion (Actual): December 27, 2019

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Padsevonil; CYP2C19; Healthy Japanese Participants
• Other Study ID Numbers: UP0083; JapicCTI-194958 (Registry Identifier: JapicCTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Due to the small sample size in this trial, Individual Patient Data cannot be adequately anonymized and there is a reasonable likelihood that individual participants could be re-identified. For this reason, data from this trial cannot be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No