A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy (X-TOLE)

A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 as Adjunctive Therapy in Focal-onset Epilepsy, With an Open-label Extension

The XEN1101 Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of increasing doses of XEN1101 administered as adjunctive treatment in adult patients diagnosed with focal epilepsy, followed by an optional open-label extension (OLE).

Study Overview

• Status: Active, not recruiting
• Conditions: Focal Epilepsy
• Intervention / Treatment: Drug: XEN1101

Detailed Description

The XEN1101 Phase 2 clinical trial is designed as a randomized, double-blind, placebo-controlled, multicenter study with an optional open-label extension (OLE) to evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive treatment in adult patients aged 18 to 75 years diagnosed with focal epilepsy. Approximately 300 patients will be randomized in a blinded manner to one of three active treatment groups or placebo in a 2:1:1:2 fashion (XEN1101 25 mg : 20 mg : 10 mg : Placebo). After screening, patients will have 8 weeks of baseline to assess frequency of seizures, followed by 8 weeks of treatment and a 6-week post treatment follow-up period. In order to be included in the study, patients must already be treated with a stable dose of 1 to 3 allowable current anti-epileptic drugs for at least one month prior to screening, during baseline, and throughout the double-blind portion (DBP) of the study. During the treatment period, patients will be given XEN1101 or placebo once daily in the evening. An OLE will be available to eligible patients who complete the DBP. All patients will receive a 20 mg daily dose of XEN1101 during this extension period.

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's and Women's Health Centre of British Columbia (BC Children's Hospital)
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Center
    • Toronto, Ontario, Canada, M5T 2S8
      • University Health Network-Toronto Western Hospital
• Georgia
  • Tbilisi, Georgia, 0112
    • LLC Arensia Exploratory Medicine
• Germany
  • Berlin, Germany, 10365
    • Epilepsiezentrum Berlin-Brandenburg
  • Bielefeld, Germany, 33617
    • Bethel Epilepsy Centre
  • Bonn, Germany, 53127
    • Univ.-Klinik Bonn, Klinik und Poliklinik fur Epileptologie
  • Frankfurt, Germany, 60528
    • Universitatsklinikym Frankfurt
  • Freiburg, Germany, 79106
    • Universitatsklinikum Freiburg, Neurozentrum/Epilepsiezentrum
  • Muenster, Germany, 48149
    • University Hospital Munster (UKM)
  • Osnabrück, Germany, 49076
    • Klinikum Osnabruck
  • Regensburg, Germany, 93049
    • Krankenhaus Barmherzige Brueder Regensburg
  • Tübingen, Germany, 72076
    • University of Tubingen-Dept. of Neurology and Epileptology
• Italy
  • Bologna, Italy, 40139
    • IRCCS- Istituto delle Scienze Neurologiche, Bellaria Hospital
  • Catanzaro, Italy, 88100
    • Dipartimento Scienze Mediche e Chirurgiche, Universita Magna Graecia di Catanzaro
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Neurologico C. Besta
  • Pavia, Italy, 27100
    • IRCCS Istituto Neurologico Nazionale C. Mondino
  • Pisa, Italy, 56124
    • Azienda Ospedaliera Universita' Pisana
  • Reggio Calabria, Italy, 89123
    • Azienda Ospedaliera "Bianchi-Melacrino-Morelle"di Reggio Calabria
  • Roma, Italy, 00185
    • Policlinico di Roma Umberto I
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, 2025
    • PMSI Republican Clinical Hospital, ARENSIA Exploratory Medicine
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Granada, Spain, 18008
    • Hospital Vithas La Salud
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28036
    • Hospital Ruber Internacional
  • Madrid, Spain, 28034
    • Hospital U. Ramón y Cajal
  • Madrid, Spain, 28040
    • Hospital U. Clínico San Carlos
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
  • Valladolid, Spain, 47003
    • Hospital Clínico Universitario Valladolid
  • Andalusia
    • Sevilla, Andalusia, Spain, 41009
      • Hospital Virgen Macarena
    • Sevilla, Andalusia, Spain, 41013
      • Centro de Neurologia Avanzada
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad Navarra
• Ukraine
  • Kyiv, Ukraine, 01135
    • Medical Center of Limited Liability Company "Harmoniya Krasy"
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom, SW17 0QT
    • St. George's University Hospitals NHS Foundation Trust
  • Scotland
    • Glasgow, Scotland, United Kingdom, G514TF
      • Institute of Neurological Sciences
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • University Hospital of Wales
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Mobile, Alabama, United States, 36604
      • Strada Patient Care Center
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenoscience, Inc.
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials, Inc.
  • California
    • La Jolla, California, United States, 92037
      • Altman Clinical Translational Research Institute (ACTRI)
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center (CPMC) - Sutter Pacific Epilepsy Program
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital Anschutz Outpatient Pavilion
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Jacksonville
    • Miami, Florida, United States, 33133
      • Visionary Investigators Network
    • Miami, Florida, United States, 33136
      • Don Clinical Research Center
    • Miami, Florida, United States, 33176
      • The Neurology Research Group, LLC.
    • Orlando, Florida, United States, 32806
      • Research Institute of Orlando, LLC
    • Port Charlotte, Florida, United States, 33952
      • Medsol Clinical Research Center
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Neurological Clinic
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Suwanee, Georgia, United States, 30024
      • Georgia Neurology and Sleep Medicine Associate
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Idaho
    • Boise, Idaho, United States, 83702
      • Consultants in Epilepsy and Neurology, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Group, Department of Neurology
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Epilepsy Research
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Partners Neurology
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Mid-Atlantic Epilepsy and Sleep Center
  • Massachusetts
    • South Dartmouth, Massachusetts, United States, 02747
      • Boston Neuro Research Center
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology, Ltd.
    • Saint Paul, Minnesota, United States, 55102
      • Minnesota Epilepsy Group, P. A.
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Northeast Regional Epilepsy Group
    • Livingston, New Jersey, United States, 07039
      • Institute of Neurology and Neurosurgery at Saint Barnabas
    • Morristown, New Jersey, United States, 07960
      • Northeast Regional Epilepsy Group
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center
    • New York, New York, United States, 10016
      • NYU Langone Medical Center/NYU School of Medicine
    • New York, New York, United States, 10075
      • Northwell Health - Lenox Hill
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Institute for Human Performance
    • Woodmere, New York, United States, 11598
      • Five Towns Neuroscience Research
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Asheville Neurology Specialists, PA
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • UC Gardner Neuroscience Institute
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Toledo, Ohio, United States, 43606
      • University of Toledo Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Neurological Specialties East
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Comprehensive Epilepsy Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Neurological Associates
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Epilepsy Clinic
  • Texas
    • Austin, Texas, United States, 78758
      • Austin Epilepsy Care Center
    • Dallas, Texas, United States, 75390
      • James W. Aston Ambulatory Care Center
    • San Antonio, Texas, United States, 78229-3900
      • The University of Texas Health Science Center at San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Clinical Neurosciences Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
    • Roanoke, Virginia, United States, 24016
      • Carilion Neurology Clinic
    • Winchester, Virginia, United States, 22601
      • Winchester Neurological Consultants
  • Washington
    • Renton, Washington, United States, 98055
      • UW Medicine Valle Medical Center
    • Seattle, Washington, United States, 98104
      • University of Washington School of Medicine, Regional Epilepsy Center at Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
• BMI ≤40 kg/m2
• Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy [ILAE] Classification of Epilepsy (2017)
• Prior neuroimaging within the last 10 years and documentation is available
• Treatment with a stable dose of 1 to 3 allowable current AEDs for at least one month prior to screening, during baseline, and throughout the duration of the DBP
• Must be willing to comply with the contraception requirements
• Males must agree not to donate sperm from the time of the first administration of study drug until 6 months after the last dose. Females must agree not to donate ova from the time of the first administration of study drug until 6 months after the last dose.
• Able to keep accurate seizure diaries

Key Exclusion Criteria:

• History of pseudoseizures, psychogenic seizures, primary generalized seizure, or focal aware non-motor seizures only
• Presence or previous history of Lennox-Gastaut syndrome
• Seizures secondary to other diseases or conditions
• History of repetitive seizures within the last 12 months where the individual seizures cannot be counted
• History of neurosurgery for seizures <1 year prior to enrollment, or radiosurgery <2 years prior to enrollment
• Schizophrenia and other psychotic disorders, or active suicidal plan/intent in the past 6 months, or a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt
• History or presence of any significant medical or surgical condition or uncontrolled medical illness at screening, or history of cancer within the past 2 years, with the exception of appropriately treated basal cell or squamous cell carcinoma

• Any clinically significant abnormalities on pre-study physical examination, vital signs, laboratory values or ECG indicating a medical problem that would preclude study participation including but not limited to:

  1. History of presence of long QT syndrome; QTcF > 450 msec at baseline; family history of sudden death of unknown cause
  2. History of skin or retinal pigment epithelium abnormalities caused by ezogabine
• Past use of vigabatrin without stable visual fields tested twice over the 12 months after the last dose of vigabatrin (concomitant use of vigabatrin is not allowed)
• If felbamate is used as a concomitant AED, patients must be taking it for at least 2 years, with a stable dose for 2 months (or no less than 49 days) and acceptable hematology and LFT history and values prior to Screening. If received in the past, felbamate must have been discontinued 2 months (or no less than 49 days) prior to Screening.
• Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions
• Current use of a ketogenic diet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsule	Drug: XEN1101; Oral dose
Experimental: 25 mg XEN1101; Capsule filled with 25 mg XEN1101	Drug: XEN1101; Oral dose
Experimental: 20 mg XEN1101; Capsule filled with 20 mg XEN1101	Drug: XEN1101; Oral dose
Experimental: 10 mg XEN1101; Capsule filled with 10 mg XEN1101	Drug: XEN1101; Oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the efficacy of XEN1101 compared to placebo on focal seizure frequency (e.g., median percent change in focal seizure frequency) in adults with focal epilepsy taking 1-3 antiepileptic drugs (AEDs) in the double-blind treatment period (DBP)	Median percent change in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo	From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)
To assess the safety and tolerability of XEN1101 (e.g., adverse events) in adults with focal epilepsy taking 1-3 AEDs	To assess adverse events as criteria for safety and tolerability	From screening (up to 28 days prior to baseline) through to 42 days post-final dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the 50% XEN1101 response rates in comparison to placebo in the DBP	Responders are defined as patients experiencing ≥50% reduction in monthly (28 days) focal seizure frequency from baseline to DBP	From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)
To evaluate trends in focal seizure frequency over time in the DBP	Percent change from baseline in weekly focal seizure frequency for each week in the DBP	From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)

Collaborators and Investigators

• Sponsor: Xenon Pharmaceuticals Inc.
• Collaborators: Novotech Health Holdings Pte. Ltd.
• Investigators: Study Director: Study Director, Xenon Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2019
• Primary Completion (Actual): September 2, 2021
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: January 2, 2019
• First Submitted That Met QC Criteria: January 7, 2019
• First Posted (Actual): January 8, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial
• Other Study ID Numbers: XPF-008-201; 2018-003221-29 (EudraCT Number)

Drug and device information, study documents

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