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

• ClinicalTrials.gov Identifier: NCT03468725
• Recruitment Status: Completed
• First Posted: March 16, 2018
• Last Update Posted: September 18, 2018
• Sponsor: Xenon Pharmaceuticals Inc.
• Information provided by (Responsible Party): Xenon Pharmaceuticals Inc.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Healthy Male Volunteers	Drug: XPF-008; Drug: Microcrystalline Cellulose	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 13, 2018
• Actual Primary Completion Date: July 31, 2018
• Actual Study Completion Date: July 31, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events (AEs) as assessed by CTCAE v4.03 [ Time Frame: 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
2. Resting 12-lead electrocardiogram (ECG) [ Time Frame: 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
3. Number of participants with vital sign abnormalities [ Time Frame: From screening (28 days prior to Day 1) through to Day 14 ]
   To assess vital signs as a criteria of safety and tolerability
4. Pharmacodynamic (PD) Effects assessed by Transcranial Magnetic Stimulation (TMS) biological markers of brain excitability [ Time Frame: Day 1 predose through to Day 7 ]
   To assess biological marker of brain excitability: amplitude (in uV) of TMS evoked potentials on the EEG
5. PD Effects assessed by TMS biological markers of brain excitability [ Time Frame: 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 Outcome Measures :

1. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 1 predose through to Day 8 ]
   Cmax is the maximum observed plasma concentration in ng/mL
2. Terminal elimination half-life (t1/2) [ Time Frame: 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
3. Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC0-last) [ Time Frame: 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 Criteria

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

Criteria

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

Contacts and Locations

Locations

United Kingdom

King's College Hospital

Brixton, London, United Kingdom, SE5 9RS

Sponsors and Collaborators

Xenon Pharmaceuticals Inc.

Investigators

• Study Director: Gregory Beatch, PhD; Xenon Pharmaceuticals Inc.

More Information

• Responsible Party: Xenon Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03468725
• Other Study ID Numbers: XPF-008-101b; 2017-003181-27 ( EudraCT Number ); C17047 ( Other Identifier: Richmond Pharmacology's Study Code )
• First Posted: March 16, 2018
• Last Update Posted: September 18, 2018
• Last Verified: September 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xenon Pharmaceuticals Inc.:

Transcranial magnetic stimulation