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

NCT03468725 — Phase 1, Completed, 20 participants, Xenon Pharmaceuticals Inc.

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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

Registry	NCT03468725
Status	Completed
Phase	Phase 1
Study type	Interventional; randomized, crossover, masking: triple, treatment
Enrollment	20 (Actual)
Sponsor	Xenon Pharmaceuticals Inc. (Industry)
Conditions	Healthy Male Volunteers
Interventions	XPF-008, Microcrystalline Cellulose (Drug)
Dates	start 2018-02-13, primary completion 2018-07-31, completion 2018-07-31, first posted 2018-03-16, last updated 2018-09-18
Locations	1 site in United Kingdom

-Summary

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.

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+Arms and interventions

Arm	Type	Interventions	Description
XPF-008	Experimental	Drug: XPF-008	Single oral dose
Placebo	Active comparator	Drug: Microcrystalline Cellulose	Single oral dose

XPF-008 (Drug): Capsule filled with XEN1101
Microcrystalline Cellulose (Drug): Placebo capsule

+Outcome measures

Primary outcomes

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

Secondary outcomes

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

+Eligibility

Sex: Male, ages: 18 Years to 55 Years, accepts healthy volunteers

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

+Locations (1)

Facility	City	Country	Status
King's College Hospital	Brixton, London	United Kingdom

+Investigators

Gregory Beatch, PhD, Study director, Xenon Pharmaceuticals Inc.

+Funding

NIH grants: 2017