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

Sponsor
Xenon Pharmaceuticals Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03796962
Collaborator
NCGS, Inc. (Industry)
300
Enrollment
95
Locations
4
Arms
68
Anticipated Duration (Months)
3.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

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. A three year 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 Design

Study Type:
Interventional
Anticipated Enrollment :
300 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jan 30, 2019
Actual Primary Completion Date :
Sep 2, 2021
Anticipated Study Completion Date :
Oct 1, 2024

Arms and Interventions

Arm Intervention/Treatment
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
Placebo Comparator: Placebo

Placebo capsule

Drug: XEN1101
Oral dose

Outcome Measures

Primary Outcome Measures

  1. 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) [From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)]

    Median percent change in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo

  2. To assess the safety and tolerability of XEN1101 (e.g., adverse events) in adults with focal epilepsy taking 1-3 AEDs [From screening (up to 28 days prior to baseline) through to 42 days post-final dose]

    To assess adverse events as criteria for safety and tolerability

Secondary Outcome Measures

  1. To evaluate the 50% XEN1101 response rates in comparison to placebo in the DBP [From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)]

    Responders are defined as patients experiencing ≥50% reduction in monthly (28 days) focal seizure frequency from baseline to DBP

  2. To evaluate trends in focal seizure frequency over time in the DBP [From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)]

    Percent change from baseline in weekly focal seizure frequency for each week in the DBP

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

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

Sponsors and Collaborators

  • Xenon Pharmaceuticals Inc.
  • NCGS, Inc.

Investigators

  • Study Director: Study Director, Xenon Pharmaceuticals Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Xenon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT03796962
Other Study ID Numbers:
  • XPF-008-201
First Posted:
Jan 8, 2019
Last Update Posted:
Aug 23, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Xenon Pharmaceuticals Inc.
Epilepsy
Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial

Study Results

No Results Posted as of Aug 23, 2022