Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of XEN901

Study Overview
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Brief Summary
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The XEN901 Phase 1 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the safety, tolerability and pharmacokinetics (PK) of both single ascending doses (SAD) and multiple ascending doses (MAD) of XEN901 in healthy subjects. It is estimated there will be approximately 64 subjects in the planned SAD and MAD cohorts.

Official Title
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Phase 1, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of XEN901 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: XEN901
* Drug: Inert Ingredients Oral Product


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy male or females aged between 18 and 55 years inclusive with a body mass index (BMI) between 18.5 and 32.0 kg/m2 Must agree to use effective methods of contraception, if applicable Able to swallow capsules Able to provide written, personally signed and dated Informed Consent Form Key Exclusion Criteria: Any history of seizures 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 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 (except hormonal contraception), herbal or dietary supplements OTC medications 14 days prior to dosing to study end No smoking 60 days prior to dosing to study end Any clinically significant abnormalities in vital signs, ECG, physical exam, or laboratory evaluations

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XEN901<br>Single ascending dose: Single oral dose for each cohort; Multiple ascending dose: 7 days of single oral dose twice daily for each cohort | Drug: XEN901<br>* Capsule filled with XEN901<br>|
| Placebo Comparator: Placebo<br>Single Ascending Dose: Single oral dose for each cohort; Multiple Ascending Dose: 7 days of single oral dose twice daily for each cohort | Drug: Inert Ingredients Oral Product<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 12-lead ECG intervals (PR, QRS, QTcF, RR) as a criteria of safety and tolerability | At screening (28 days prior to Day 1) through to 7 days post-final dose | 
| Number of participants with vital sign abnormalities | To assess vital signs as a criteria of safety and tolerability | At screening (28 days prior to Day 1) through to 7 days post-final dose | 

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 7 days post-final dose | 
| Time to the Maximum Observed Plasma Concentration (Tmax) | Tmax is the time in hours to reach Cmax following dosing | Day 1 predose through to 7 days post-final dose | 
| 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 7 days post-final dose | 
| 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 7 days post-final dose |