A Study to Test the Safety and Tolerability of Single and Multiple Doses of Padsevonil in Adult and Elderly Study Participants

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the plasma pharmacokinetic of padsevonil in adult and elderly study participants.

Official Title
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An Open-Label, Parallel-Group, Pharmacokinetic, Safety and Tolerability Study of Single and Multiple Oral Administrations of Padsevonil in Adult and Elderly Study Participants

Conditions
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Elderly Study Participants, Adult Study Participants

Intervention / Treatment
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* Drug: Padsevonil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Adult study participants<br>Participants will receive assigned single and multiple doses of padsevonil. | Drug: Padsevonil<br>* Padsevonil will be administered in predefined dosages.<br>|
| Experimental: Elderly study participants<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 |
| --- | --- | --- |
| The Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL) | Cmax was measured in nanograms per milliliter (ng/mL). | 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 | 
| The Area Under the Curve From 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL) | AUC0-t: area under the plasma concentration-time curve from time 0 to the last quantifiable concentration. It was measured in hours times nanograms per milliliter (h*ng/mL). | 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 | 
| The Area Under the Curve (AUC) of a Single Dose Padsevonil (PSL) | AUC was measured in hours times nanograms per milliliter (h*ng/mL). | 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 | 
| The Maximum Plasma Concentration at Steady-state (Cmax, ss) of Multiple Doses Padsevonil (PSL) | Cmax, ss was measured in nanograms per milliliter (ng/mL). | 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 | 
| The Area Under the Curve (AUCtau) Over a Dosing Interval of Multiple Doses Padsevonil (PSL) | AUCtau was measured in hours times nanograms per milliliter (h*ng/mL). | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Amount of Padsevonil (PSL) Excreted in Urine | Samples were taken to assess the amount of padsevonil that was excreted in urine. Ae,ss refers to cumulative amount of PSL excreted in the urine at steady state. | Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13 | 
| The Ratio of Padsevonil (PSL) to Its Metabolites Excreted in Urine | Samples were taken to assess the metabolic ratio of padsevonil that was excreted in urine. MRAe was defined as the metabolic ratio of PSL to its metabolites for cumulative amount of PSL metabolites excreted in the urine. ss refers to steady state. | Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13 | 
| Number of Participants With Treatment-emergent Adverse Events | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication. | From Baseline until End-of-Treatment visit (up to Day 22) | 
| Number of Participants With Serious Adverse Events | A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalization or prolongation of existing hospitalization Is a congenital anomaly or birth defect Is an infection that requires treatment parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above | From Baseline until End-of-Treatment visit (up to Day 22) | 
| Number of Participants With Treatment-emergent Adverse Events Leading to Discontinuation of the Study | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline until End-of-Treatment visit (up to Day 22) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Padsevonil, Phase 1, Pharmacokinetic