A Study to Test the Blood Concentration of 4 Padsevonil Product Variants and the Effect of Food on Padsevonil

Study Overview
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Brief Summary
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The purpose of the study in Part 1, is to evaluate (under fasted conditions) the plasma pharmacokinetics (PK) of padsevonil (PSL) using 4 PSL product variants against a PSL reference tablet and in Part 2, to evaluate the PK of PSL using a PSL reference tablet under fed and fasted conditions at 200 mg and 400 mg.

Official Title
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An Open-Label, Randomized, Single-Dose, 2-Part Crossover Study in Healthy Study Participants to Evaluate the Relative Bioavailability of 4 Padsevonil Product Variants and the Effect of Food on Padsevonil

Conditions
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Healthy Participants, Epilepsy

Intervention / Treatment
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* Drug: Padsevonil type 1 Tablet 200 mg
* Drug: Padsevonil type 2 Tablet
* Drug: Padsevonil type 3 Tablet
* Drug: Padsevonil type 4 Tablet
* Drug: Padsevonil type 5 Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent form (ICF) Study participants must be overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring Study participants must have a body weight of at least 50 kg for males and 45 kg for females and body mass index within the range 18 to 35 kg/m2 (inclusive) Study participants who are male or female: A male participant must agree to use contraception during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days (or 5 terminal half-lives) after the last dose of study medication Exclusion Criteria: 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 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 a history or presence of/significant history 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 history or present condition of respiratory or cardiovascular disorders, (eg, cardiac insufficiency, coronary heart disease, hypertension, arrhythmia, tachyarrhythmia, or myocardial infarction) 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 used hepatic enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, isoniazid, phenytoin, rifampicin, etc) within 2 months prior to the first dose of study medication. In case of uncertainty, the Medical Monitor should be consulted Study participant has participated in another study of an investigational study medication (and/or an investigational device) within the previous 60 days before Screening (or 5 half-lives, whichever is longer) or is currently participating in another study of an investigational study medication (and/or an investigational device) Study participant has made a blood donation or has had a comparable blood loss (>400 mL) within the last 3 months prior to the Screening Visit or has made plasma donation within last month prior to the Screening Visit Study participant smokes more than 5 cigarettes per day (or equivalent) or has done so within 6 months prior to the Screening Visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: In Part 1 a single oral dose of padsevonil 200 mg for the 4 different product variants and the padsevonil reference tablet will be administered to all subjects in the fasted state in a randomized 5-way crossover design. In order to explore the food interaction with padsevonil, in Part 2 a single oral dose of a padsevonil reference tablet at dose levels of 200 mg and 400 mg (2x 200mg tablets) will be administered to all subjects in the fasted and fed state in a randomized 4-way crossover study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Type 1 tablet - part 1<br>Subjects will receive a single dose of padsevonil Type 1 tablet in the period defined by the pre-specified sequence they were randomized on to. | Drug: Padsevonil type 1 Tablet 200 mg<br>* Pharmaceutical form: Film-coated tablet Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.<br>|
| Experimental: Type 2 tablet - part 1<br>Subjects will receive a single dose of padsevonil Type 2 tablet in the period defined by the pre-specified sequence they were randomized on to. | Drug: Padsevonil type 2 Tablet<br>* Pharmaceutical form: Film-coated tablet Route of administration: Oral use Subjects will receive a padsevonil type 2 tablet in a pre-specified sequence during the Treatment Period<br>|
| Experimental: Type 3 tablet - part 1<br>Subjects will receive a single dose of padsevonil Type 3 tablet in the period defined by the pre-specified sequence they were randomized on to. | Drug: Padsevonil type 3 Tablet<br>* Pharmaceutical form: Film-coated tablet Route of administration: Oral use Subjects will receive a padsevonil type 3 tablet in a pre-specified sequence during the Treatment Period.<br>|
| Experimental: Type 4 tablet - part 1<br>Subjects will receive a single dose of padsevonil Type 4 tablet in the period defined by the pre-specified sequence they were randomized on to. | Drug: Padsevonil type 4 Tablet<br>* Pharmaceutical form: Film-coated tablet Route of administration: Oral use Subjects will receive a padsevonil type 4 tablet in a pre-specified sequence during the Treatment Period.<br>|
| Experimental: Type 5 tablet - part 1<br>Subjects will receive a single dose of padsevonil Type 5 tablet in the period defined by the pre-specified sequence they were randomized on to. | Drug: Padsevonil type 5 Tablet<br>* Pharmaceutical form: Film-coated tablet Route of administration: Oral use Subjects will receive a padsevonil type 5 tablet in a pre-specified sequence during the Treatment Period.<br>|
| Active Comparator: Type 1 tablet - part 2 (2 x 200 mg fasted)<br>Subjects will receive a single 2 x 200 mg dose of padsevonil Type 1 tablet under fasting conditions in the period defined by the pre-specified sequence they were randomized on to. | Drug: Padsevonil type 1 Tablet 200 mg<br>* Pharmaceutical form: Film-coated tablet Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.<br>|
| Active Comparator: Type 1 tablet - part 2 (2 x 200 mg fed)<br>Subjects will receive a single 2 x 200 mg dose of padsevonil Type 1 tablet under fed conditions in the period defined by the pre-specified sequence they were randomized on to. | Drug: Padsevonil type 1 Tablet 200 mg<br>* Pharmaceutical form: Film-coated tablet Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.<br>|
| Active Comparator: Type 1 tablet - part 2 (200 mg fasted)<br>Subjects will receive a single 200 mg dose of padsevonil Type 1 tablet under fasting conditions in the period defined by the pre-specified sequence they were randomized on to. | Drug: Padsevonil type 1 Tablet 200 mg<br>* Pharmaceutical form: Film-coated tablet Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.<br>|
| Active Comparator: Type 1 tablet - part 2 (200 mg fed)<br>Subjects will receive a single 200 mg dose of padsevonil Type 1 tablet under fed conditions in the period defined by the pre-specified sequence they were randomized on to. | Drug: Padsevonil type 1 Tablet 200 mg<br>* Pharmaceutical form: Film-coated tablet Route of administration: Oral use Subjects will receive a padsevonil type 1 tablet in a pre-specified sequence during the Treatment Period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t of padsevonil type 1 tablets during part 1 | AUC(0-t): Area under the plasma concentration-time curve from time zero to time t | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC0-t of padsevonil type 2 tablets during part 1 | AUC(0-t): Area under the plasma concentration-time curve from time zero to time t | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC0-t of padsevonil type 3 tablets during part 1 | AUC(0-t): Area under the plasma concentration-time curve from time zero to time t | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC0-t of padsevonil type 4 tablets during part 1 | AUC(0-t): Area under the plasma concentration-time curve from time zero to time t | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC0-t of padsevonil type 5 tablets during part 1 | AUC(0-t): Area under the plasma concentration-time curve from time zero to time t | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC0-t of padsevonil type 1 tablets (2x200 mg, fasted) during part 2 | AUC(0-t): Area under the plasma concentration-time curve from time zero to time t | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| AUC0-t of padsevonil type 1 tablets (2x200 mg, fed) during part 2 | AUC(0-t): Area under the plasma concentration-time curve from time zero to time t | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| AUC0-t of padsevonil type 1 tablets (200 mg, fasted) during part 2 | AUC(0-t): Area under the plasma concentration-time curve from time zero to time t | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| AUC0-t of padsevonil type 1 tablets (200 mg, fed) during part 2 | AUC(0-t): Area under the plasma concentration-time curve from time zero to time t | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| AUC of padsevonil type 1 tablets during part 1 | AUC: Area under the concentration-time curve from time 0 to infinity | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC of padsevonil type 2 tablets during part 1 | AUC: Area under the concentration-time curve from time 0 to infinity | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC of padsevonil type 3 tablets during part 1 | AUC: Area under the concentration-time curve from time 0 to infinity | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC of padsevonil type 4 tablets during part 1 | AUC: Area under the concentration-time curve from time 0 to infinity | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC of padsevonil type 5 tablets during part 1 | AUC: Area under the concentration-time curve from time 0 to infinity | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| AUC of padsevonil type 1 tablets (400 mg, fasted) during part 2 | AUC: Area under the concentration-time curve from time 0 to infinity | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| AUC of padsevonil type 1 tablets (400 mg, fed) during part 2 | AUC: Area under the concentration-time curve from time 0 to infinity | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| AUC of padsevonil type 1 tablets (200 mg, fasted) during part 2 | AUC: Area under the concentration-time curve from time 0 to infinity | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| AUC of padsevonil type 1 tablets (200 mg, fed) during part 2 | AUC: Area under the concentration-time curve from time 0 to infinity | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| Cmax of padsevonil type 1 tablets during part 1 | Cmax: Maximum observed plasma concentration | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| Cmax of padsevonil type 2 tablets during part 1 | Cmax: Maximum observed plasma concentration | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| Cmax of padsevonil type 3 tablets during part 1 | Cmax: Maximum observed plasma concentration | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| Cmax of padsevonil type 4 tablets during part 1 | Cmax: Maximum observed plasma concentration | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| Cmax of padsevonil type 5 tablets during part 1 | Cmax: Maximum observed plasma concentration | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 1. | 
| Cmax of padsevonil type 1 tablets (400 mg, fasted) during part 2 | Cmax: Maximum observed plasma concentration | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| Cmax of padsevonil type 1 tablets (400 mg, fed) during part 2 | Cmax: Maximum observed plasma concentration | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| Cmax of padsevonil type 1 tablets (200 mg, fasted) during part 2 | Cmax: Maximum observed plasma concentration | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 
| Cmax of padsevonil type 1 tablets (200 mg, fed) during part 2 | Cmax: Maximum observed plasma concentration | Plasma samples will be taken at: predose and 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 ,12, 24, 36, 48, 60, and 72 hours during part 2. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. | From Baseline up to Day 35 | 
| Incidence of Serious Adverse Events (SAEs) | 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 up to Day 35 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Padsevonil, Bioavailability, Food effect