Resumen

Este es un estudio de fase 3, multicéntrico, aleatorizado, doble ciego, controlado con placebo, para evaluar la eficacia clínica, seguridad y tolerabilidad de XEN1101 administrado como tratamiento complementario en crisis tónico-clónicas generalizadas primarias (CTCGP).

Descripción detallada

Este es un estudio de fase 3, multicéntrico, aleatorizado, doble ciego, controlado con placebo, para evaluar la eficacia clínica, seguridad y tolerabilidad de XEN1101 administrado como tratamiento complementario en sujetos diagnosticados con epilepsia generalizada que presentan CTCGP probables o posibles (con o sin otros subtipos de crisis generalizadas), y que toman de 1 a 3 medicamentos anticrisis (MAC). Los sujetos elegibles serán asignados aleatoriamente 1:1 a XEN1101 o placebo: los sujetos de ≥ 18 años recibirán XEN1101 25 mg o placebo, y los sujetos de ≥12 y <18 años recibirán XEN1101 15 mg, 25 mg o placebo. La aleatorización será estratificada según la región, el grupo etario y el uso de fondo de MAC inductores de CYP3A4. Los sujetos elegibles tendrán hasta 9,5 semanas de duración para evaluar la frecuencia basal de crisis, seguido de un período de tratamiento doble ciego (PDC) donde los sujetos recibirán 12 semanas de tratamiento a ciegas. Durante el PDC, se instruirá a los sujetos para que tomen XEN1101 o placebo por vía oral una vez al día con la cena. Los sujetos que completen el PDC de 12 semanas tendrán la oportunidad de inscribirse en un estudio separado de extensión abierta (EA) para continuar el tratamiento con XEN1101. Los sujetos que no se inscriban en la EA ingresarán a un período de seguimiento postratamiento de 8 semanas.

Elegibilidad

Edad mínima: 12 YearsSexo: ALL

Criterios de inclusión

Subject is properly informed of the nature and risks of the study and gives informed consent in writing prior to entering the study (for adult subjects) and for adolescent subjects parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study.
Subject is ≥12 years of age with a BMI ≤40 kg/m2 at Visit 1.
Subject must have had adequate trials of at least 2 ASMs, which were given (and tolerated) at adequate therapeutic doses, without achieving sustained seizure freedom.
Subject has probable or possible PGTCS (with or without other subtypes of generalized seizures) for ≥1 year, in the setting of generalized epilepsy according to the International League Against Epilepsy 2017 classification criteria, and subject is approved by The Epilepsy Study Consortium (TESC).
Subject is on a stable dose of 1 to 3 allowable current ASMs for at least 1 month prior to screening (Visit 1), during screening/baseline, and throughout the DBP.
Subject is able to keep accurate seizure diaries.

Criterios de exclusión

Subject has had status epilepticus within the 12 months prior to Visit 1.
Subject has history of repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
Subject has a history of non-epileptic psychogenic seizures.
Subject has a concomitant diagnosis of focal-onset seizures (FOS).
Subject has presence or history of a developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
Subject has seizures secondary to drug or alcohol use, ongoing infection, neoplasia, demyelinating disease, degenerative neurological disease, metabolic illness, progressive structural lesion, encephalopathy, or progressive central nervous system (CNS) disease.
Subject has history of neurosurgery for seizures \<1 year prior to Visit 1, or radiosurgery \<2 years prior to Visit 1.
Subject has schizophrenia and other psychotic disorders (eg, schizophreniform disorder, schizoaffective disorder, psychosis not otherwise specified), bipolar disorder, obsessive-compulsive disorder, or another serious mental health disorder. Subject has uncontrolled unipolar major depression where changes in pharmacotherapy are needed or anticipated during the study.
Subject has any clinically significant laboratory abnormalities or clinically significant abnormalities on prestudy physical examination, vital signs, or ECG that, in the judgment of the investigator, indicate a medical problem that would preclude study participation, including but not limited to:
a. History or presence of long QT syndrome; QTcF \>450 msec at baseline; family history of sudden death of unknown cause.
Any personal circumstance that, in the opinion of the investigator, prevents adherence to the protocol.
The criteria to be eligible for randomization are:
During the last 56 days of the baseline period that preceded the randomization visit (Visit 2), subject must have had a sufficient documented seizure frequency of PGTCS, including ≥1 PGTCS during each of the first and second 4-week periods preceding randomization.
Seizure diary was completed a minimum of 80% of all days (ie, ≥45 days) during the last 56 days of the baseline period that preceded randomization as evidence of adequate compliance.
Subject did not change dose of, stop, or initiate any new ASM(s) during the baseline period and plans on maintaining a stable dose of ASM(s) during the DBP.

Intervenciones

drug

XEN1101

XEN1101 capsules

drug

Placebo

Placebo capsules

Ubicaciones

Hospital General de Agudos J.M. Ramos Mejia

Buenos Aires, Argentina

RECRUITING

STAT Research S.A.

Buenos Aires, Argentina

RECRUITING

Hospital Italiano

Buenos Aires, Argentina

RECRUITING

Sanatorio del Sur S.A

San Miguel de Tucumán, Argentina

RECRUITING

Patrocinadores

PrincipalXenon Pharmaceuticals Inc.

ColaboradorWorldwide Clinical Trials

Contactos

Xenon Medical Affairs

CONTACT

XenonCares@xenon-pharma.com 1-604-484-3300

Estudio de fase 3, aleatorizado, doble ciego, controlado con placebo, multicéntrico, para evaluar la seguridad, tolerabilidad y eficacia de XEN1101 como terapia complementaria en crisis tónico-clónicas generalizadas primarias

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

XEN1101

Placebo

Ubicaciones

Hospital General de Agudos J.M. Ramos Mejia

STAT Research S.A.

Hospital Italiano

Sanatorio del Sur S.A

Patrocinadores

Contactos

Xenon Medical Affairs