Abstract Details

Title A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Safety and Efficacy of XEN1101 as an Adjunctive Therapy in the Treatment of Primary Generalized Tonic-Clonic Seizures

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 9-012

Objective Describe the rationale and study design of X-ACKT, a randomized, double-blind, placebo-controlled Phase 3 study to evaluate the safety and efficacy of XEN1101 as an adjunctive therapy in the treatment of primary generalized tonic-clonic seizures (PGTCS).

Background XEN1101 is a novel, potent, selective K_v7.2/7.3 potassium channel opener which shows broad spectrum seizure suppression in preclinical models. In epilepsy patients with photosensitivity, ICA-105665, a K_v7 potassium channel opener no longer in development, suppressed paroxysmal EEG activity (Kasteleijn-Nolst Trenité et al, Epilepsia. 2013;54(8)). These data support the broad-spectrum anti-seizure potential of XEN1101 and provide the rationale for a PGTCS trial.

Design/Methods X-ACKT is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the PK, safety and efficacy of XEN1101 in the fed state in adults aged 18-75 years with a seizure frequency of ≥3 PGTCS over an 8-week baseline, taking 1-3 anti-seizure medications (ASMs). Approximately 160 subjects will be randomized at 1:1 (25mg:placebo) to a 12-week double-blind period (DBP) following an 8-week baseline period to assess seizure frequency. Subjects completing the DBP may be eligible for an open-label extension (OLE) trial under a separate protocol.

Results The primary efficacy endpoint is median percent change in monthly PGTCS frequency from baseline. The key secondary outcomes are the proportion of subjects experiencing ≥50% reduction in monthly PGTCS frequency from baseline (RR50), seizure freedom and the Patient Global Impression of Change compared to baseline. Safety will be evaluated by severity and frequency of treatment emergent adverse events (AEs) and serious AEs; clinically significant changes in clinical laboratory findings, physical, neurologic and ophthalmologic exams, ECGs, vital signs, and urinary symptoms will also be evaluated.

Conclusions X-ACKT will provide insight into the safety, tolerability, and efficacy of XEN1101 as adjunctive therapy in the treatment of PGTCS and is designed to support registration of XEN1101 for the treatment of PGTCS.

Authors/Disclosures
Cynthia L. Harden, MD (Xenon Pharmaceuticals Inc) PRESENTER	Dr. Harden has received personal compensation for serving as an employee of Xenon Pharmaceuticals Inc.. Dr. Harden has stock in Xenon Pharmaceuticals Inc.. Dr. Harden has received intellectual property interests from a discovery or technology relating to health care.
Antonio Gil-Nagel, MD (Hospital Ruber Internacional)	Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EISAI . Dr. Gil-Nagel has received personal compensation in the range of $0-$499 for serving as a Consultant for GW Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Angelini Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GW Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoke . Dr. Gil-Nagel has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zogenix . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Angelini Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIAL . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EISAI . Dr. Gil-Nagel has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for GW Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Jazz Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for PTC Therapeutics . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zogenix . The institution of Dr. Gil-Nagel has received research support from Jazz Pharmaceuticals. The institution of Dr. Gil-Nagel has received research support from PTC Therapeutics. The institution of Dr. Gil-Nagel has received research support from Zogenix. The institution of Dr. Gil-Nagel has received research support from Agencia Estatal Innovacion.
David G. Vossler, MD, FAAN (David G. Vossler MD FAAN FAES FACNS)	Dr. Vossler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Longboard Pharmaceuticals. Dr. Vossler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Xenon Pharmaceuticals. Dr. Vossler has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for SK Life Science. The institution of Dr. Vossler has received research support from Xenon Pharmaceuticals. The institution of Dr. Vossler has received research support from Longboard Pharmaceuticals. Dr. Vossler has received publishing royalties from a publication relating to health care.
Elinor Ben-Menachem, MD, FAAN (Dept of Clinical Neuroscience)	Dr. Ben-Menachem has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Ben-Menachem has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arvelle. Dr. Ben-Menachem has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GW Pharma. Dr. Ben-Menachem has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Acta Neurologica Scandinvica. The institution of Dr. Ben-Menachem has received research support from zogenic.
W. C. LaFrance, Jr., MD, MPH, FAAN (Rhode Island Hospital)	Dr. LaFrance has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for medico-legal work.. The institution of Dr. LaFrance has received research support from Department of Defense. Dr. LaFrance has received publishing royalties from a publication relating to health care. Dr. LaFrance has received publishing royalties from a publication relating to health care. Dr. LaFrance has a non-compensated relationship as a Steering Committee Member with Xenon that is relevant to AAN interests or activities.
Jenny Qian	Jenny Qian has nothing to disclose.
Gregory N. Beatch, PhD	Dr. Beatch has received personal compensation for serving as an employee of Xenon Pharmaceuticals Inc. Dr. Beatch has stock in Xenon Pharmaceuticals Inc. Dr. Beatch has received intellectual property interests from a discovery or technology relating to health care.
Christopher Kenney	No disclosure on file

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