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

NCT04075409 | Completed Phase 1 Results

• 2 other identifiers: UP0083JapicCTI-194958
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Japanese Participants

Keywords

Padsevonil; CYP2C19; Healthy Japanese Participants; Pharmacokinetics

Outcome Measures

Primary Outcomes (10)

• 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)

Study Arms (3)

Extensive metabolizers

EXPERIMENTAL

Participants will receive assigned single and multiple doses of padsevonil.

Drug: Padsevonil

Intermediate metabolizers

EXPERIMENTAL

Participants will receive assigned single and multiple doses of padsevonil.

Drug: Padsevonil

Poor metabolizers

EXPERIMENTAL

Participants will receive assigned single and multiple doses of padsevonil.

Drug: Padsevonil

Interventions

Padsevonil DRUG

Padsevonil will be administered in predefined dosages.

Extensive metabolizers; Intermediate metabolizers; Poor metabolizers

Eligibility Criteria

• Age: 20 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Biopharma S.P.R.L.: lead

Study Sites (1)

Up0083 001

Tokyo, Japan

Location

Related Publications (1)

• Chanteux H, MacPherson M, Kramer H, Otoul C, Okagaki T, Rospo C, De Bruyn S, Watling M, Bani M, Sciberras D. Overview of preclinical and clinical studies investigating pharmacokinetics and drug-drug interactions of padsevonil. Expert Opin Drug Metab Toxicol. 2024 Aug;20(8):841-855. doi: 10.1080/17425255.2024.2373108. Epub 2024 Jul 9.

  PMID: 38932723 DERIVED

MeSH Terms

Interventions

padsevonil

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

+1844599

Study Officials

• UCB Cares

  001 844 599 2273 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2019
• First Posted: August 30, 2019
• Study Start: September 30, 2019
• Primary Completion: December 27, 2019
• Study Completion: December 27, 2019
• Last Updated: July 8, 2021
• Results First Posted: July 8, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)