A multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of padsevonil as adjunctive treatment of focal-onset seizures in adult subjects with drug-resistant epilepsy

Phase 3

Withdrawn

• Conditions: Epilepsy; falling disease; 10029305

• Registration Number: NL-OMON49060
• Lead Sponsor: CB Biopharma SR

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 15

Inclusion Criteria

Inclusion criteria,
General,
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
approved written informed consent form (ICF) is signed and dated by the subject
or by the parent(s) or legal representative, where applicable. The ICF or a
specific Assent form, where required, will be signed and dated according to
country-specific regulations.
2. Subject/legal representative is considered reliable and capable of adhering
to the protocol (eg, able to understand and complete diaries), visit schedule,
and medication intake according to the judgment of the Investigator.
3. Subject is an adult (18 years of age or more).
4. Subject is of normal weight of at least 40 kg (for males and females).,
Epilepsy,
5. Subject fulfills diagnostic criteria for epilepsy and has observable
focal-onset (IA1, IB, and IC) seizures for at least 3 years at the time of
enrollment (according to the International League Against Epilepsy [ILAE]
Classification of Epileptic Seizures, 1981):
- Epileptic seizures have been documented using video-electroencephalogram
(EEG) recordings or ictal EEG (±simultaneous video) in the past (description or
report is available). The Investigator must consult with the UCB Study
Physician or representative for confirmation of eligibility as per instructions
in the Study Manual.
If no video-EEG report is available and, in the opinion of the Investigator,
epileptic seizures are definite (ie, eye-witnessed seizure report, home video
documentation of habitual events, or other proof), the Investigator must
consult with the UCB Study Physician or representative for a case review.
- A brain magnetic resonance imaging (MRI) is to be performed before
randomization, if no such scan was performed in the last 10 years, and a report
is not available. If a scan was performed within the last 10 years but the
clinical condition of the subject was progressive since the last scan, a new
scan should be obtained. If MRI is contraindicated, a head computed tomography
scan within the last 3 years before randomization will suffice.
6. Subject has on average *4 spontaneous and observable focal-onset seizures
per 28 days (based on Investigator assessment of subject report) with at least
1 seizure during each 4 week interval of the 8 weeks prior to the Screening
Visit. Additionally, subject must experience *4 spontaneous and observable
focal-onset seizures per 28 days (based on Investigator assessment of subject
report) during the 4-week Baseline Period.
7. Subject has failed to achieve seizure control with *4 tolerated and
appropriately chosen prior AEDs, including past and ongoing treatments that
were individually optimized for adequate dose and duration. Prior discontinued
AED treatment would need to be assessed by the Investigator considering the
patient medical records and patient and/or caregiver interview. Prior AED is
defined as all past and ongoing AED treatments with a start date before the
Screening Visit (Visit 1).,
Concomitant epilepsy treatment,
8. Subject is currently treated with an individually optimized and stable dose
of at least 1 and up to 3 AEDs for the 8 weeks prior to the Screening Visit
(Visit 1) with or without additional concurrent vagus nerve stimulation (VNS)
or other neurostimulation treatments. The latter will not be coun

Exclusion Criteria

Exclusion criteria,
General,
1. Subject has previously been randomized in this study, or a study of the
medication under investigation in this study. Re-screening of a subject may be
permitted but requires prior Medical Monitor approval and is not permitted in
case of screen failure due to seizure count.
2. Subject has participated in another study of an investigational medication
(or a medical device) within the previous 30 days or 5 half-lives (whichever is
longer) or is currently participating in another study of an investigational
medication (or a medical device).
Laboratory parameters
3. Subject has either:
- >2.0x upper limit of normal (ULN) of any of the following:
* alanine aminotransferase (ALT).
* aspartate aminotransferase (AST).
* alkaline phosphatase (ALP).
-OR-
- >ULN total bilirubin (*1.5xULN total bilirubin if known Gilbert*s syndrome).
If subject has elevations only in total bilirubin that are >ULN and <1.5xULN,
fractionate bilirubin to identify possible undiagnosed Gilbert*s syndrome (ie,
direct bilirubin <35%).
For randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total
bilirubin, a Baseline diagnosis and/or the cause of any clinically meaningful
elevation must be understood and recorded.
If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at
screening, repeat the tests, if possible, prior to dosing to ensure there is no
further ongoing clinically relevant increase. In case of a clinically relevant
increase, inclusion of the subject must be discussed with the Medical Monitor.
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may
be repeated once for confirmation before Baseline (Visit 2).,
Medical conditions,
4. Subject has a history or current medical condition that, in the opinion of
the Investigator, could jeopardize or would compromise the subject*s ability to
participate in this study.
5. Subject has a current psychiatric condition that occurred within the last 12
months which, in the opinion of the Investigator, could compromise the
subject*s safety or ability to participate in this study, including but not
limited to schizophrenia, schizoaffective disorder, bipolar disorder, severe
unipolar depression, dementia, or irreversible severe or progressive
encephalopathy.
6. Subject has a lifetime history of suicide attempt (including an actual
attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in
the past 6 months as indicated by a positive response (*Yes*) to either
question 4 or question 5 of the *Screening/Baseline* version of the
Columbia-Suicide Severity Rating Scale (C-SSRS) at screening.
7. Subject has a history of chronic alcohol or drug abuse within the last 2
years.
8. Subject has a history of cerebrovascular accident, including transient
ischemic attack, in the last 6 months.
9. Subject has presence of any sign (clinical or imaging techniques) suggesting
rapidly progressing (ie, not expected to stay stable during study
participation) brain disorder or brain tumor. Stable lesions such as
arteriovenous malformations, meningiomas, or other benign tumors are acceptable
if no surgical removal is planned or likely for the duration of the study.
10. Subject has any clinical condition (eg, bone marrow depression, chronic
h

Study & Design

• Study Type: Interventional
• Study Design: Not specified