Study to Test the Safety and Efficacy of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy

• ClinicalTrials.gov Identifier: NCT03370120
• Recruitment Status: Terminated
• First Posted: December 12, 2017
• Results First Posted: December 29, 2021
• Last Update Posted: December 29, 2021
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Drug-Resistant Epilepsy; Focal-Onset Seizures
• Intervention: Drug: Padsevonil
• Enrollment: 406

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.

Arm/Group Title	Padsevonil
Arm/Group Description	Participants received padsevonil tablets at a dose of 100 milligrams/day (mg/day) to 800 mg/day up to approximately 2 years.
Period Title: Overall Study
Started	406
Completed	0
Not Completed	406
Reason Not Completed
Adverse event, non-fatal	24
Withdrawal by Subject	6
Lost to Follow-up	1
Lack of Efficacy	37
Per sponsor's instructions	1
Study was terminated by parent company UCB	2
The study was ended by the promoter	3
Discontinuation of drug development	3
End of project	2
Premature study closure	2
Premature program termination	1
Premature study termination	7
Trial terminated by sponsor	2
Trial discontinued by sponsor	2
Study ended	15
Clinical trial has been cancelled	1
End of study per sponsor decision	2
Promoter's decision	2
The trial has been suspended	3
Sponsor stopped PSL development based on data	3
Early termination by order of sponsor	2
Discontinuation of the study	5
End of clinical trial discontinuation	1
Because the clinical trial ended halfway	4
Development discontinued	5
Padsenovil program closed	3
End of project	2
Termination of project	1
The study was interrupted by sponsor	4
The protocol was interrupted by sponsor	1
End of sponsor decision	1
The study was terminated prematurely by study lead	1
Early termination of studies	5
This study is ended early	1
End of padsevonil program	2
Decision of sponsor	6
Asked by the sponsor	3
Sponsor decision to stop the protocol	1
PI decision poor compliance from participant	1
Promoter ended the study	3
Premature study close by sponsor's decision	4
Study terminated by sponsor	33
Sponsor prematurely terminated this study	2
Sponsor decision to terminate study	63
Program closure	3
Study ended prematurely	1
Study stopped by sponsor	2
Program termination	55
Sponsor decision	62
Sponsor study closure	10

Baseline Characteristics

Arm/Group Title		Padsevonil
Arm/Group Description		Participants received PSL tablets at a dose of 100 mg/day to 800 mg/day up to approximately 2 years.
Overall Number of Baseline Participants		406
Baseline Analysis Population Description		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 Case Report form (CRF).
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	406 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	395 97.3%
	>=65 years	11 2.7%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	406 participants
		40.8 (12.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	406 participants
	Female	231 56.9%
	Male	175 43.1%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	406 participants
American Indian / Alaskan native		5 1.2%
Asian		38 9.4%
Black		6 1.5%
Native Hawaiian or other Pacific Islander		5 1.2%
White		343 84.5%
Other/mixed		9 2.2%

Outcome Measures

1. Primary Outcome

Title	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
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Padsevonil (SS)
Arm/Group Description:	Participants received PSL tablets at a dose of 100 mg/day to 800 mg/day up to approximately 2 years. Participants formed the Safety Set (SS).
Overall Number of Participants Analyzed	406
Measure Type: Number; Unit of Measure: percentage of participants
	72.2

2. Primary Outcome

Title	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Padsevonil (SS)
Arm/Group Description:	Participants received PSL tablets at a dose of 100 mg/day to 800 mg/day up to approximately 2 years. Participants formed the SS.
Overall Number of Participants Analyzed	406
Measure Type: Number; Unit of Measure: percentage of participants
	5.2

3. Primary Outcome

Title	Change From Baseline (From the Respective Parent Study [EP0091 or EP0092]) in Observable Focal-onset Seizure Frequency Over the Evaluation Period
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Padsevonil (FAS)
Arm/Group Description:	Participants received PSL tablets at a dose of 100 mg/day to 800 mg/day up to approximately 2 years. Participants formed the FAS.
Overall Number of Participants Analyzed	406
Mean (Standard Deviation); Unit of Measure: seizures per 28 days
	-7.73 (27.52)

Adverse Events

Time Frame	From Entry Visit (Week 0) until the Safety Follow-up Visit (up to approximately 2 years)
Adverse Event Reporting Description	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.
Arm/Group Title	Padsevonil (SS)
Arm/Group Description	Participants received PSL tablets at a dose of 100 mg/day to 800 mg/day up to approximately 2 years. Participants formed the SS.
All-Cause Mortality
	Padsevonil (SS)
	Affected / at Risk (%)
Total	0/406 (0.00%)
Serious Adverse Events
	Padsevonil (SS)
	Affected / at Risk (%)	# Events
Total	48/406 (11.82%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion * 1	1/406 (0.25%)	1
Gastrointestinal disorders
Abdominal discomfort * 1	1/406 (0.25%)	1
Large intestinal haemorrhage * 1	1/406 (0.25%)	1
Nausea * 1	1/406 (0.25%)	1
Vomiting * 1	1/406 (0.25%)	1
Hepatobiliary disorders
Bile duct stone * 1	1/406 (0.25%)	1
Cholecystitis * 1	1/406 (0.25%)	1
Cholelithiasis * 1	1/406 (0.25%)	1
Infections and infestations
Corona virus infection * 1	1/406 (0.25%)	1
Cytomegalovirus infection * 1	1/406 (0.25%)	1
Gastroenteritis viral * 1	1/406 (0.25%)	1
Pneumonia * 1	1/406 (0.25%)	1
Wound infection * 1	1/406 (0.25%)	1
Injury, poisoning and procedural complications
Head injury * 1	1/406 (0.25%)	1
Ulna fracture * 1	1/406 (0.25%)	1
Investigations
Mycoplasma test positive * 1	1/406 (0.25%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer * 1	1/406 (0.25%)	1
Phyllodes tumour * 1	1/406 (0.25%)	1
Nervous system disorders
Cervical radiculopathy * 1	1/406 (0.25%)	1
Epilepsy * 1	7/406 (1.72%)	8
Focal dyscognitive seizures * 1	2/406 (0.49%)	2
Generalised tonic-clonic seizure * 1	5/406 (1.23%)	8
Migraine * 1	1/406 (0.25%)	1
Partial seizures * 1	1/406 (0.25%)	1
Partial seizures with secondary generalisation * 1	2/406 (0.49%)	3
Postictal state * 1	1/406 (0.25%)	1
Seizure * 1	4/406 (0.99%)	4
Seizure cluster * 1	2/406 (0.49%)	2
Status epilepticus * 1	5/406 (1.23%)	5
Syncope * 1	1/406 (0.25%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous * 1	1/406 (0.25%)	1
Pregnancy * 1	1/406 (0.25%)	1
Psychiatric disorders
Aggression * 1	1/406 (0.25%)	1
Suicide Attempt * 1	1/406 (0.25%)	1
Renal and urinary disorders
Acute kidney injury * 1	1/406 (0.25%)	1
Pelvi-ureteric obstruction * 1	1/406 (0.25%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration * 1	1/406 (0.25%)	1
Skin and subcutaneous tissue disorders
Drug Eruption * 1	1/406 (0.25%)	1
Drug reaction with eosinophilia and systemic symptoms * 1	2/406 (0.49%)	2
Surgical and medical procedures
Hip arthroplasty * 1	1/406 (0.25%)	1
Vagal nerve stimulator implantation * 1	1/406 (0.25%)	1
Vascular disorders
Hypotension * 1	1/406 (0.25%)	1
1 Term from vocabulary, MedDRA v22.1; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Padsevonil (SS)
	Affected / at Risk (%)	# Events
Total	184/406 (45.32%)
General disorders
Fatigue * 1	47/406 (11.58%)	56
Infections and infestations
Nasopharyngitis * 1	29/406 (7.14%)	42
Nervous system disorders
Somnolence * 1	66/406 (16.26%)	76
Headache * 1	59/406 (14.53%)	138
Dizziness * 1	43/406 (10.59%)	63
Memory impairment * 1	21/406 (5.17%)	38
Psychiatric disorders
Insomnia * 1	23/406 (5.67%)	27
1 Term from vocabulary, MedDRA v22.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: UCB
• Organization: Cares
• Phone: 001-844-599-2273
• EMail: UCBCares@ucb.com

• Responsible Party: UCB Pharma ( UCB Biopharma SRL )
• ClinicalTrials.gov Identifier: NCT03370120
• Other Study ID Numbers: EP0093; 2017-003241-26 ( EudraCT Number )
• First Submitted: December 7, 2017
• First Posted: December 12, 2017
• Results First Submitted: November 30, 2021
• Results First Posted: December 29, 2021
• Last Update Posted: December 29, 2021