Drug-Resistant Epilepsy, Focal-Onset Seizures
Conditions
Keywords
Drug-Resistant Epilepsy, Padsevonil
Brief summary
The purpose of the study is to evaluate the long-term safety and tolerability of Padsevonil administered at individualized doses as adjunctive treatment for subjects with drug-resistant epilepsy.
Interventions
DRUGPadsevonil
* Pharmaceutical Form: film-coated tablet * Route of Administration: Oral use
Sponsors
UCB Biopharma SRL
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is an adult (18 years of age or more ) * Subject with epilepsy who has completed 1 of the previous Padsevonil (PSL) studies which allow access to the present study * 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 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 Subjects will be withdrawn from the study as soon as pregnancy is known.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.
Exclusion criteria
* Subject has any severe medical, neurological, or psychiatric condition, or laboratory value which may have an impact on the safety of the subject * Subject has 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) * Subject has \>2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or \>ULN total bilirubin (\>= l.5x ULN total bilirubin if known Gilbert's syndrome) at the Entry Visit * Subject has a clinically-significant abnormality on electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study * Subject has an abnormality on echocardiogram at last echocardiogram assessment, or foreseen in parent study as assessed by central reader that is accompanied by clinical symptoms or a Grade 2\* (or higher)/moderate severity abnormality, or a history of rheumatic heart disease, or other known valvular abnormalities (\*according to the ASE Guidelines, 2017; Zoghbi et al 2017) * Female subject who plans to be pregnant or is breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Participant and/or Caregiver or Observed by the Investigator During the Entire Study | From Entry Visit (Week 0) until the Safety Follow-up Visit (up to approximately 2 years) | An Adverse Event is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event that was not present prior to the initiation of the first dose of study treatment in this study or any unresolved event already present before initiation of the first dose that worsens in intensity following exposure to the treatment. |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal | From Entry Visit (Week 0) until the Safety Follow-up Visit (up to approximately 2 years) | An Adverse Event is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event that was not present prior to the initiation of the first dose of study treatment in this study or any unresolved event already present before initiation of the first dose that worsens in intensity following exposure to the treatment. |
| Change From Baseline (From the Respective Parent Study [EP0091 or EP0092]) in Observable Focal-onset Seizure Frequency Over the Evaluation Period | From Baseline in respective parent study over the Evaluation Period (up to approximately 2 years) in this study | Seizure frequency refers to 28-day adjusted frequency. Observable focal-onset seizures refer to Type IAl, IB, and IC (according to the International League Against Epilepsy (ILAE) Classification of Epileptic Seizures, 1981). Focal-onset seizures include all Type I seizures. |
Countries
Australia, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Croatia, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Lithuania, Mexico, Poland, Romania, Serbia, Slovakia, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study started to enroll study participants in August 2018 and concluded in December 2020.
Pre-assignment details
Participant Flow refers to the Safety Set. Participants who had completed a padsevonil (PSL) parent study (EP0091 \[NCT03373383\] or EP0092 \[NCT03739840\]) were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Padsevonil Participants received PSL tablets at a dose of 100 mg/day to 800 mg/day up to approximately 2 years. | 406 |
| Total | 406 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse event, non-fatal | 24 |
| Overall Study | Asked by the sponsor | 3 |
| Overall Study | Because the clinical trial ended halfway | 4 |
| Overall Study | Clinical trial has been cancelled | 1 |
| Overall Study | Decision of sponsor | 6 |
| Overall Study | Development discontinued | 5 |
| Overall Study | Discontinuation of drug development | 3 |
| Overall Study | Discontinuation of the study | 5 |
| Overall Study | Early termination by order of sponsor | 2 |
| Overall Study | Early termination of studies | 5 |
| Overall Study | End of clinical trial discontinuation | 1 |
| Overall Study | End of padsevonil program | 2 |
| Overall Study | End of project | 2 |
| Overall Study | End of sponsor decision | 1 |
| Overall Study | End of study per sponsor decision | 2 |
| Overall Study | Lack of Efficacy | 37 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Padsenovil program closed | 3 |
| Overall Study | Per sponsor's instructions | 1 |
| Overall Study | PI decision poor compliance from participant | 1 |
| Overall Study | Premature program termination | 1 |
| Overall Study | Premature study close by sponsor's decision | 4 |
| Overall Study | Premature study closure | 2 |
| Overall Study | Premature study termination | 7 |
| Overall Study | Program closure | 3 |
| Overall Study | Program termination | 55 |
| Overall Study | Promoter ended the study | 3 |
| Overall Study | Promoter's decision | 2 |
| Overall Study | Sponsor decision | 62 |
| Overall Study | Sponsor decision to stop the protocol | 1 |
| Overall Study | Sponsor decision to terminate study | 63 |
| Overall Study | Sponsor prematurely terminated this study | 2 |
| Overall Study | Sponsor stopped PSL development based on data | 3 |
| Overall Study | Sponsor study closure | 10 |
| Overall Study | Study ended | 15 |
| Overall Study | Study ended prematurely | 1 |
| Overall Study | Study stopped by sponsor | 2 |
| Overall Study | Study terminated by sponsor | 33 |
| Overall Study | Study was terminated by parent company UCB | 2 |
| Overall Study | Termination of project | 1 |
| Overall Study | The protocol was interrupted by sponsor | 1 |
| Overall Study | The study was ended by the promoter | 3 |
| Overall Study | The study was interrupted by sponsor | 4 |
| Overall Study | The study was terminated prematurely by study lead | 1 |
| Overall Study | The trial has been suspended | 3 |
| Overall Study | This study is ended early | 1 |
| Overall Study | Trial discontinued by sponsor | 2 |
| Overall Study | Trial terminated by sponsor | 2 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Padsevonil |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 395 Participants |
| Age, Continuous | 40.8 years STANDARD_DEVIATION 12.5 |
| Race/Ethnicity, Customized American Indian / Alaskan native | 5 Participants |
| Race/Ethnicity, Customized Asian | 38 Participants |
| Race/Ethnicity, Customized Black | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 5 Participants |
| Race/Ethnicity, Customized Other/mixed | 9 Participants |
| Race/Ethnicity, Customized White | 343 Participants |
| Sex: Female, Male Female | 231 Participants |
| Sex: Female, Male Male | 175 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 406 |
| other Total, other adverse events | 184 / 406 |
| serious Total, serious adverse events | 48 / 406 |
Outcome results
Primary
Change From Baseline (From the Respective Parent Study [EP0091 or EP0092]) in Observable Focal-onset Seizure Frequency Over the Evaluation Period
Seizure frequency refers to 28-day adjusted frequency. Observable focal-onset seizures refer to Type IAl, IB, and IC (according to the International League Against Epilepsy (ILAE) Classification of Epileptic Seizures, 1981). Focal-onset seizures include all Type I seizures.
Time frame: From Baseline in respective parent study over the Evaluation Period (up to approximately 2 years) in this study
Population: Full Analysis Set (FAS) consisted of all enrolled participants who were administered at least 1 dose of PSL or a partial dose of PSL and completed at least 1 seizure diary during the Evaluation Period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Padsevonil (SS) | Change From Baseline (From the Respective Parent Study [EP0091 or EP0092]) in Observable Focal-onset Seizure Frequency Over the Evaluation Period | -7.73 seizures per 28 days | Standard Deviation 27.52 |
Primary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal
An Adverse Event is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event that was not present prior to the initiation of the first dose of study treatment in this study or any unresolved event already present before initiation of the first dose that worsens in intensity following exposure to the treatment.
Time frame: From Entry Visit (Week 0) until the Safety Follow-up Visit (up to approximately 2 years)
Population: The SS consisted of all enrolled participants who were administered at least 1 dose of PSL, based on the first dose date from the first administration of study medication CRF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Padsevonil (SS) | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal | 5.2 percentage of participants |
Primary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Participant and/or Caregiver or Observed by the Investigator During the Entire Study
An Adverse Event is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event that was not present prior to the initiation of the first dose of study treatment in this study or any unresolved event already present before initiation of the first dose that worsens in intensity following exposure to the treatment.
Time frame: From Entry Visit (Week 0) until the Safety Follow-up Visit (up to approximately 2 years)
Population: The Safety Set (SS) consisted of all enrolled participants who were administered at least 1 dose of PSL, based on the first dose date from the first administration of study medication CRF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Padsevonil (SS) | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Participant and/or Caregiver or Observed by the Investigator During the Entire Study | 72.2 percentage of participants |