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

Phase 1
Completed
Conditions
Healthy Male Volunteers
Interventions
Registration Number
NCT03468725
Lead Sponsor
Xenon Pharmaceuticals Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
20
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
XPF-008XPF-008Single oral dose
PlaceboMicrocrystalline CelluloseSingle oral dose
Primary Outcome Measures
NameTimeMethod
Number of participants with adverse events (AEs) as assessed by CTCAE v4.03From 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 abnormalitiesFrom 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 excitabilityDay 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 excitabilityDay 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
NameTimeMethod
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

Trial Locations

Locations (1)

King's College Hospital

🇬🇧

Brixton, London, United Kingdom

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