Safety, Tolerability, Pharmacokinetics and Effects on Transcranial Magnetic Stimulation of Oral Doses of XEN1101

Study Overview
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Brief Summary
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The XEN1101 Phase 1 clinical trial is a randomized, double-blind, placebo-controlled study that will eventuate the safety, tolerability, pharmacokinetics (PK) and effects on transcranial magnetic stimulation (TMS) of oral doses of XEN1101 in healthy male subjects.The TMS procedure is designed to demonstrate delivery of XEN1101 into the central nervous system and to observe a change in cortical excitability as measured by EEG and/or EMG activity. It is estimated there will be approximately 15 subjects in the planned study.

Official Title
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A Double-blind, Placebo-controlled Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Effects on Transcranial Magnetic Stimulation of Oral Administration of XEN1101 in Healthy Male Subjects

Conditions
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Healthy Male Volunteers

Intervention / Treatment
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* Drug: XPF-008
* Drug: Microcrystalline Cellulose


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy male aged between 18 and 55 years inclusive with a body mass index (BMI) between 18.5 and 30.0 kg/m2 Right-handed only Must agree to use effective methods of contraception, if applicable Able to swallow multiple capsules Able to provide written, personally signed and dated Informed Consent Form Key Exclusion Criteria: Any current and relevant history of significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk, affect clinical or laboratory results, or the subject's ability to participate in the study Any clinically significant abnormalities in vital signs, ECGs, physical examinations, or laboratory evaluations Answering yes to any of the questions within the Columbia Suicide Severity Rating Scale Mental incapacity or language barriers precluding adequate understanding, cooperation, and compliance with the study No prescription or over-the-counter (OTC) medications (including multivitamins, herbal or homeopathic preparations 14 days or if applicable/available, 5 half-lives prior to dosing to study end Any history of severe head trauma No smoking 60 days prior to dosing to study end

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XPF-008<br>Single oral dose | Drug: XPF-008<br>* Capsule filled with XEN1101<br>|
| Active Comparator: Placebo<br>Single oral dose | Drug: Microcrystalline Cellulose<br>* Placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) as assessed by CTCAE v4.03 | To assess AEs as a criteria of safety and tolerability | From screening (28 days prior to Day 1) through to 30 days post-final dose | 
| Resting 12-lead electrocardiogram (ECG) | To assess ECG intervals (PR, QRS, QTcF, RR) as a criteria of safety and tolerability | From screening (28 days prior to Day 1) through to Day 14 | 
| Number of participants with vital sign abnormalities | To assess vital signs as a criteria of safety and tolerability | From screening (28 days prior to Day 1) through to Day 14 | 
| Pharmacodynamic (PD) Effects assessed by Transcranial Magnetic Stimulation (TMS) biological markers of brain excitability | To assess biological marker of brain excitability: amplitude (in uV) of TMS evoked potentials on the EEG | Day 1 predose through to Day 7 | 
| PD Effects assessed by TMS biological markers of brain excitability | To assess biological marker of brain excitability: resting motor threshold (in %) for elicitation of an electromyographic response | Day 1 predose through to Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Cmax is the maximum observed plasma concentration in ng/mL | Day 1 predose through to Day 8 | 
| Terminal elimination half-life (t1/2) | The time in hours required for the plasma level of the study drug to decrease by one-half during the terminal elimination phase | Day 1 predose through to Day 8 | 
| Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC0-last) | The area under the plasma concentration-time curve [in ng.h/mL] from time zero to the time corresponding to the last quantifiable plasma concentration | Day 1 predose through to Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial magnetic stimulation