An open-label, multicenter, extension study to evaluate the safety and efficacy of padsevonil as adjunctive treatment of focal-onset seizures in adult subjects with drug resistant epilepsy

Phase 2

Withdrawn

• Conditions: Epilepsy; falling disease; 10029305

• Registration Number: NL-OMON49972
• Lead Sponsor: CB Biopharma SPR

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• Status: Withdrawn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

General
1. An Institutional Review Board/Independent Ethics Committee approved written
informed consent form (ICF) is signed and dated by the subject or by the
parent(s) or legal representative (where legally permitted). The ICF or a
specific Assent form, where required, will be signed and dated by minors,
according to country-specific regulations.
2. Subject/legal representative/caregiver (where legally permitted) is
considered reliable and capable of adhering to the protocol (eg, able to
understand and complete diaries), visit schedule, or medication intake
according to the judgment of the Investigator.
3. Subject is an adult (*18 years of age)., Epilepsy
4. Subject with epilepsy who has completed 1 of the previous PSL studies which
allow access to the present study.
Birth control
5. Female subjects of child bearing potential must have a serum negative
pregnancy test at the Entry Visit, which is confirmed to be negative by urine
testing prior to further dispensing of PSL at each study visit thereafter.
Subjects will be withdrawn from the study as soon as pregnancy is known.
Female subjects will use an efficient form of contraception for the duration of
the study and for a period of 3 months after their final dose of PSL. Hormonal
contraception may be susceptible to an interaction with PSL, which may reduce
the efficacy of the contraception method. The potential for reduced efficacy of
any hormonal contraception method requires that a barrier method (preferably a
condom) also be used.
Birth control methods considered as efficient forms of contraception:
- Combined (estrogen- and progesterone-containing) hormonal contraception
(oral, implant, injectable) in combination with a barrier method (preferably a
condom).
- Progesterone-only hormonal contraceptives (oral, implant, injectable) in
combination with a barrier method (preferably a condom).
- Progesterone-releasing intrauterine systems or the TCu 380A intrauterine
device in combination with a barrier method (preferably a condom).
- Male or female condom with spermicide (ie, double-barrier).
- Cap, diaphragm or sponge with spermicide (ie, double-barrier).
- Bilateral tubal ligation.
- Vasectomized partner.
- True heterosexual sexual abstinence. Periodic abstinence (eg, calendar,
ovulation, symptothermal, post-ovulation methods), declaration of abstinence
for the duration of the study, and withdrawal are not acceptable methods of
contraception.
- Women not agreeing to use birth control must be of nonchildbearing potential,
defined as being postmenopausal, or permanently sterilized (eg, bilateral tubal
occlusion, hysterectomy, bilateral salpingectomy), or congenitally sterile.
- Both male and female subjects must use the above-mentioned contraception
during the study.
- To ensure a proper birth control, females who use hormonal contraception
should use an efficient barrier contraceptive in the 3 months after their final
intake of PSL.

Exclusion Criteria

A subject will be excluded from the study if she/he has:, General
1. Any severe medical, neurological, or psychiatric condition, or laboratory
value which may have an impact on the safety of the subject.
2. Active suicidal ideation as indicated by a positive response (*Yes*) to
either Question 4 or Question 5 of the *Since Last Visit* version of the
Columbia-Suicide Severity Rating Scale (C-SSRS). The subject should be referred
immediately to a mental healthcare professional and must be withdrawn from the
study.
Laboratory parameters
3. More than 2x 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) at the Entry Visit. If the subject has elevations only in total
bilirubin that are >ULN and <1.5xULN, fractionated bilirubin must be used to
identify possible undiagnosed Gilbert*s syndrome (ie, direct bilirubin <35%).
For enrolled subjects with a Baseline result >ULN for ALT, AST, ALP, or total
bilirubin, a Baseline diagnosis and/or the cause of any clinically-significant
elevation must be understood and recorded.
If subject has >ULN for ALT, AST, or ALP that does not meet the exclusion limit
at the Entry Visit (ie, the value is >ULN but *2xULN at the Entry Visit of
EP0093), the tests must be repeated, if possible, prior to dosing to ensure
there is no further ongoing clinically significant increase. In case of a
clinically-significant increase, inclusion of the subject must be discussed
with the Medical Monitor., Medical conditions
4. A clinically significant abnormality on electrocardiogram (ECG) that, in the
opinion of the Investigator, increases the risks associated with participating
in the study. In addition, any subject with any of the following findings will
be excluded:
- QT interval corrected for heart rate using Bazett*s formula (QTcB) or QT
interval corrected for heart rate using Fridericia*s formula (QTcF) >450ms.
- Bundle branch blocks and other conduction abnormalities that are clinically
significant according to the Investigator and/or with a PR interval *220ms,
irregular rhythms other than sinus arrhythmia or occasional, rare
supraventricular or rare ventricular ectopic beats in the judgment of the
Investigator, or T-wave configurations are not of sufficient quality for
assessing QT interval duration.
- Subject has a history of unexplained syncope or a family history of sudden
death due to long QT syndrome.
5. An abnormality on echocardiogram at last echocardiogram assessment, or
foreseen in parent study as assessed by central reader that is accompanied by
clinical symptoms (eg, shortness of breath, palpitations, and murmur) or a
Grade 2 (or higher)/moderate severity abnormality, or a history of rheumatic
heart disease, or other known valvular abnormalities., Pregnancy
6. Female subject who plans to be pregnant or is breastfeeding.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Criteria for evaluation:<br /><br><br /><br>Efficacy:<br /><br>Primary efficacy variables<br /><br>* Change from Baseline (from the respective parent study) in observable<br /><br>focal-onset seizure frequency over the Evaluation Period.<br /><br><br /><br>Pharmacokinetics and Pharmacodynamics:<br /><br>No Pharmacokinetic or pharmacodynamic variables will be assessed in this study.<br /><br><br /><br>Safety:<br /><br>Primary safety variables<br /><br>* Incidence of treatment-emergent adverse events (TEAEs) reported by the<br /><br>subject and/or caregiver or observed by the Investigator.<br /><br>* Incidence of TEAEs leading to study withdrawal.</p><br>