Clinical trial NCT04013191: A Study to Test the Safety and Tolerability of Single and Multiple Doses of Padsevonil in Adult and Elderly Study Participants
Official title: An Open-Label, Parallel-Group, Pharmacokinetic, Safety and Tolerability Study of Single and Multiple Oral Administrations of Padsevonil in Adult and Elderly Study Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Elderly Study Participants
Adult Study Participants
Keywords: Padsevonil
Phase 1
Pharmacokinetic
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2019-07-09
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to evaluate the plasma pharmacokinetic of padsevonil in adult and elderly study participants.


Eligibility criteria: Inclusion Criteria:

* Study participants in the adult cohort must be ≥18 to 64 years of age at the time of signing the informed consent form (ICF)
* Study participants in the elderly cohort must be ≥65 years of age at the time of signing the ICF
* Study participants who are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring. In addition, elderly study participants must be considered to be in general good physical and mental health
* Study participants must have a body weight of at least 50 kg for males and 45 kg for females, and a body mass index within the range of 18 to 32 kg/m2 (inclusive)

Exclusion Criteria:

* Study participant has a current or past psychiatric condition that, in the opinion of the Investigator, could compromise the study participant's safety or ability to participate in this study, or 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
* Study participant has 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
* Study participant has a known hypersensitivity to any components of the study medication as stated in this protocol
* Subject has a history of unexplained syncope or a family history of sudden death due to long QT syndrome
* Study participant has abnormal blood pressure
* Study participant has had lymphoma, leukemia, or any malignancy within the past 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
* Study participant has a lifetime history of suicide 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
* Study participant has past or intended use of over-the-counter or prescription medication, including herbal medications within 2 weeks or 5 half-lives prior to dosing
* The study participant has used hepatic enzyme-inducing drugs within 2 months prior to dosing
* Study participant has previously received padsevonil (PSL) in this or another study
* Study participant has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) \>1.0x upper limit of normal (ULN)
* Study participant has bilirubin \>1.0xULN (isolated bilirubin \>1.0xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
* Study 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)
* Study participant has any clinically relevant electrocardiogram (ECG) finding at Screening or at Baseline. Study participant has an abnormality in the 12-lead ECG that, in the opinion of the Investigator, increases the risks associated with participating in the study. In addition, any study participant with any of the following findings will be excluded: (a) QT interval corrected for heart rate using Bazett's formula (QTcB) or Fridericia's formula (QTcF) \>450 ms in study participants in 2 of 3 ECG recordings; (b) other conduction abnormalities (defined as PR interval ≥220 ms); (c) irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular or rare ventricular ectopic beats. In case of an out of range result, 1 repeat will be allowed. If out of range again, the study participant cannot be included

Primary outcomes:
measure: The Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL)
timeFrame: Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose
measure: The Area Under the Curve From 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL)
timeFrame: Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose
measure: The Area Under the Curve (AUC) of a Single Dose Padsevonil (PSL)
timeFrame: Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose
measure: The Maximum Plasma Concentration at Steady-state (Cmax, ss) of Multiple Doses Padsevonil (PSL)
timeFrame: Plasma samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 12 hours on Day 13
measure: The Area Under the Curve (AUCtau) Over a Dosing Interval of Multiple Doses Padsevonil (PSL)
timeFrame: Plasma samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 12 hours on Day 13
Secondary outcomes:
measure: The Amount of Padsevonil (PSL) Excreted in Urine
timeFrame: Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13
measure: The Ratio of Padsevonil (PSL) to Its Metabolites Excreted in Urine
timeFrame: Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: From Baseline until End-of-Treatment visit (up to Day 22)
measure: Number of Participants With Serious Adverse Events
timeFrame: From Baseline until End-of-Treatment visit (up to Day 22)
measure: Number of Participants With Treatment-emergent Adverse Events Leading to Discontinuation of the Study
timeFrame: From Baseline until End-of-Treatment visit (up to Day 22)
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Up0053 001
state: Texas
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: