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

Healthy Male Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03468725
• Other study ID #: XPF-008-101b
• Secondary ID: 2017-003181-27C1
• Status: Completed
• Phase: Phase 1
• Start date: February 13, 2018
• Est. completion date: July 31, 2018

Study information

• Verified date: September 2018
• Source: Xenon Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 31, 2018
• Est. primary completion date: July 31, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Male Volunteers

Intervention

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

Locations

Country	Name	City	State
United Kingdom	King's College Hospital	Brixton	London

Sponsors (1)

Lead Sponsor	Collaborator
Xenon Pharmaceuticals Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Maximum Observed Plasma Concentration (Cmax)	Cmax is the maximum observed plasma concentration in ng/mL	Day 1 predose through to Day 8
Secondary	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
Secondary	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