Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of XEN1101

• Sponsor: Xenon Pharmaceuticals Inc. (Industry)
• Overall Status: Unknown status
• CT.gov ID: NCT03340220
• Collaborator: (none)
• Enrollment: 64
• Locations: 2
• Arms: 2
• Anticipated Duration (Months): 25.5
• Patients Per Site: 32
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The XEN1101 Phase 1 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the safety, tolerability and PK of both single ascending doses (SAD) and multiple ascending doses (MAD) of XEN1101 in healthy subjects. In addition to safety and PK data, the clinical trial has been designed to include a pharmacodynamic read-out by incorporating a pilot transcranial magnetic stimulation (TMS) sub-study. The TMS model sub-study 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 64 subjects in the planned SAD and MAD cohorts.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: XPF-008; Drug: Microcrystalline Cellulose	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase 1, First-in-human, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and PK of Single and Multiple Ascending Oral Doses of XEN1101 and Preliminary Open-label Pharmacodynamic Assessment in Healthy Subjects
• Actual Study Start Date: Oct 16, 2017
• Anticipated Primary Completion Date: Dec 1, 2019
• Anticipated Study Completion Date: Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: XPF-008 Single ascending dose: Single oral dose for each cohort Multiple ascending dose: 7 days of single oral dose daily for each cohort	Drug: XPF-008; Capsule filled with XEN1101
Placebo Comparator: Placebo - Microcrystalline cellulose Single Ascending Dose: Single oral dose for each cohort Multiple Ascending Dose: 7 days of single oral dose daily for each cohort	Drug: Microcrystalline Cellulose; Placebo capsule

Outcome Measures

Primary Outcome Measures

1. 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

2. Resting electrocardiogram (ECG) [At screening (28 days prior to Day 1) through to 7 days post-final dose]

   To assess ECG as a criteria of safety and tolerability

3. Vital signs [At screening (28 days prior to Day 1) through to 7 days post-final dose]

   To assess vital signs as a criteria of safety and tolerability

Secondary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [Day 1 predose through to 7 days post-final dose]

   Cmax is the maximum observed plasma concentration in ng/mL

2. Time to the Maximum Observed Plasma Concentration (Tmax) [Day 1 predose through to 7 days post-final dose]

   Tmax is the time in hours to reach Cmax following dosing

3. Terminal elimination half-life (t1/2) [Day 1 predose through to 7 days post-final dose]

   The time in hours required for the plasma level of the study drug to decrease by one-half during the terminal elimination phase

4. 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 7 days post-final dose]

   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

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Key Inclusion Criteria:

• Healthy male or females aged between 18 and 55 years inclusive with a body mass index (BMI) between 18.50 and 30.00 kg/m2

• Must agree to use effective methods of contraception, if applicable

• Able to swallow capsules

• Able to provide written, personally signed and dated ICF

Key Exclusion Criteria:

• Any history of epileptic seizures

• 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

• Answering "yes" to any of the questions within the Columbia Suicide Severity Rating Scale

• Mental incapacity or lingual barriers precluding adequate understanding, cooperation, and compliance with the study

• No prescription or over-the-counter (OTC) medications (except hormonal contraception), herbal or dietary supplements OTC medications 14 days prior to dosing to study end

• No smoking 60 days prior to dosing to study end

• No soft drugs 3 months prior to Screening and hard drugs 2 years prior to Screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Richmond Pharmacology Ltd.	London		United Kingdom	SE1 1YR
2	King's College Hospital	London		United Kingdom	SE5 9RS

Sponsors and Collaborators

• Xenon Pharmaceuticals Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Xenon Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03340220
• Other Study ID Numbers: XPF-008-101a; 2017-003168-11; C17030
• First Posted: Nov 13, 2017
• Last Update Posted: Jul 22, 2019
• Last Verified: Jul 1, 2019

• 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

Study Results

No Results Posted as of Jul 22, 2019