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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Male Volunteers
• Intervention / Treatment: Drug: XPF-008; Drug: Microcrystalline Cellulose

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London
    • Brixton, London, United Kingdom, SE5 9RS
      • King's College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xenon Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2018
• Primary Completion (Actual): July 31, 2018
• Study Completion (Actual): July 31, 2018

Study Registration Dates

• First Submitted: March 2, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (Actual): March 16, 2018

Study Record Updates

• Last Update Posted (Actual): September 18, 2018
• Last Update Submitted That Met QC Criteria: September 14, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Transcranial magnetic stimulation
• Other Study ID Numbers: XPF-008-101b; 2017-003181-27 (EudraCT Number); C17047 (Other Identifier: Richmond Pharmacology's Study Code)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No