Clinical Trial Results:
An Openlabel, Multicenter, Extension Study to Evaluate the Longterm Safety, Tolerability, and Efficacy of UCB0942 When Used as Adjunctive Therapy for Partialonset Seizures in Adult Subjects With Highly Drugresistant Focal Epilepsy
Summary


EudraCT number 
201500126820 
Trial protocol 
NL DE BE BG HU ES IT 
Global end of trial date 
24 Nov 2020

Results information


Results version number 
v1(current) 
This version publication date 
13 Dec 2021

First version publication date 
13 Dec 2021

Other versions 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
EP0073


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT02625090  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
UCB Biopharma SRL


Sponsor organisation address 
Allée de la Recherche 60, Brussels, Belgium, 1070


Public contact 
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com


Scientific contact 
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
21 Dec 2020


Is this the analysis of the primary completion data? 
Yes


Primary completion date 
24 Nov 2020


Global end of trial reached? 
Yes


Global end of trial date 
24 Nov 2020


Was the trial ended prematurely? 
Yes


General information about the trial


Main objective of the trial 
To evaluate the longterm safety and tolerability of UCB0942 at individualized doses between 100 milligrams (mg)/day to a maximum of 800 mg/day in participants with highly drugresistant focal epilepsy


Protection of trial subjects 
During the conduct of the study all participants were closely monitored, including review of echocardiograms to detect cardiac adverse events.


Background therapy 
Background therapy as permitted in the protocol.  
Evidence for comparator 
Not applicable  
Actual start date of recruitment 
03 Dec 2015


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
Yes


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Belgium: 6


Country: Number of subjects enrolled 
Bulgaria: 2


Country: Number of subjects enrolled 
Germany: 7


Country: Number of subjects enrolled 
Hungary: 3


Country: Number of subjects enrolled 
Netherlands: 3


Country: Number of subjects enrolled 
Spain: 21


Worldwide total number of subjects 
42


EEA total number of subjects 
42


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
42


From 65 to 84 years 
0


85 years and over 
0



Recruitment


Recruitment details 
The study started to enroll study participants in December 2015 and concluded in November 2020.  
Preassignment


Screening details 
Participant flow refers to the Safety Set. Participants who experienced substantial benefit from UCB0942 with acceptable tolerability in the EP0069 (NCT02495844) study had opportunity to continue treatment in this study.  
Period 1


Period 1 title 
Overall Study (overall period)


Is this the baseline period? 
Yes  
Allocation method 
Not applicable


Blinding used 
Not blinded  
Arms


Arm title

UCB0942  
Arm description 
All enrolled participants continued the same UCB0942 dose which they were receiving during last visit of study EP0069 and the dose could be further increased or decreased in participants to optimize the drug tolerability and seizure control for each participant. Daily UCB0942 filmcoated tablets were administered orally in doses of 100 milligrams (mg) (50 mg twice daily [bid]), 200 mg (100 mg bid), 400 mg (200 mg bid), 600 mg (300 mg bid), or 800 mg (400 mg bid) for up to approximately 5 years.  
Arm type 
Experimental  
Investigational medicinal product name 
UCB0942


Investigational medicinal product code 
UCB0942


Other name 
Padsevonil


Pharmaceutical forms 
Filmcoated tablet


Routes of administration 
Oral use


Dosage and administration details 
All enrolled participants received UCB0942 filmcoated tablets daily administered orally during the study allowed in doses 100 mg (50 mgbid), bid), 200 mg (100mg bid), 400 mg (200 mg bid), 600 mg (300 mg bid), or 800 mg (400 mg bid) for up to approximately 5 years.





Baseline characteristics reporting groups


Reporting group title 
UCB0942


Reporting group description 
All enrolled participants continued the same UCB0942 dose which they were receiving during last visit of study EP0069 and the dose could be further increased or decreased in participants to optimize the drug tolerability and seizure control for each participant. Daily UCB0942 filmcoated tablets were administered orally in doses of 100 milligrams (mg) (50 mg twice daily [bid]), 200 mg (100 mg bid), 400 mg (200 mg bid), 600 mg (300 mg bid), or 800 mg (400 mg bid) for up to approximately 5 years.  



End points reporting groups


Reporting group title 
UCB0942


Reporting group description 
All enrolled participants continued the same UCB0942 dose which they were receiving during last visit of study EP0069 and the dose could be further increased or decreased in participants to optimize the drug tolerability and seizure control for each participant. Daily UCB0942 filmcoated tablets were administered orally in doses of 100 milligrams (mg) (50 mg twice daily [bid]), 200 mg (100 mg bid), 400 mg (200 mg bid), 600 mg (300 mg bid), or 800 mg (400 mg bid) for up to approximately 5 years.  
Subject analysis set title 
UCB0942 (SS)


Subject analysis set type 
Safety analysis  
Subject analysis set description 
All enrolled participants continued the same UCB0942 dose which they were receiving during last visit of study EP0069 and the dose could be further increased or decreased in participants to optimize the drug tolerability and seizure control for each participant. Daily UCB0942 filmcoated tablets were administered orally in doses of 100 mg (50 mg bid), 200 mg (100 mg bid), 400 mg (200 mg bid), 600 mg (300 mg bid), or 800 mg (400 mg bid) for up to approximately 5 years. Participants formed the Safety Set (SS).


Subject analysis set title 
UCB0942 (FAS)


Subject analysis set type 
Full analysis  
Subject analysis set description 
All enrolled participants continued the same UCB0942 dose which they were receiving during last visit of study EP0069 and the dose could be further increased or decreased in participants to optimize the drug tolerability and seizure control for each participant. Daily UCB0942 filmcoated tablets were administered orally in doses of 100 mg (50 mg bid), 200 mg (100 mg bid), 400 mg (200 mg bid), 600 mg (300 mg bid), or 800 mg (400 mg bid) for up to approximately 5 years. Participants formed the FAS.



End point title 
Percentage of participants experiencing at least one TreatmentEmergent Adverse Event (TEAE) from the beginning at Entry Visit (EV) of the Evaluation Period to End of Safety FollowUp Visit during the EP0073 study ^{[1]}  
End point description 
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Percentage of participants experiencing at least one treatmentemergent adverse event (reported by the participant and/or caregiver or observed by the Investigator or inpatient staff) are reported. The Safety Set (SS) consisted of all enrolled study participants who took at least 1 dose of UCB0942 in the EP0073 study.


End point type 
Primary


End point timeframe 
From Entry Visit to End of Safety FollowUp Visit (up to 5 years)


Notes [1]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month 0 to 3) over the Evaluation Period ^{[2]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The full analysis set (FAS) consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month 03)


Notes [2]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >36) over the Evaluation Period ^{[3]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >36)


Notes [3]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >69) over the Evaluation Period ^{[4]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >69)


Notes [4]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >912) over the Evaluation Period ^{[5]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >912)


Notes [5]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >1215) over the Evaluation Period ^{[6]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >1215)


Notes [6]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >1518) over the Evaluation Period ^{[7]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >1518)


Notes [7]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >1821) over the Evaluation Period ^{[8]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >1821)


Notes [8]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >2124) over the Evaluation Period ^{[9]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >2124)


Notes [9]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >2427) over the Evaluation Period ^{[10]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >2427)


Notes [10]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >2730) over the Evaluation Period ^{[11]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >2730)


Notes [11]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >3033) over the Evaluation Period ^{[12]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >3033)


Notes [12]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >3336) over the Evaluation Period ^{[13]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >3336)


Notes [13]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >3639) over the Evaluation Period ^{[14]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >3639)


Notes [14]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >3942) over the Evaluation Period ^{[15]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >3942)


Notes [15]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >4245) over the Evaluation Period ^{[16]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >4245)


Notes [16]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >4548) over the Evaluation Period ^{[17]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >4548)


Notes [17]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >4851) over the Evaluation Period ^{[18]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >4851)


Notes [18]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >5154) over the Evaluation Period ^{[19]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >5154)


Notes [19]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
75% Responder Rate by 3month interval (Month >5457) over the Evaluation Period ^{[20]}  
End point description 
A 75% responder is defined as a participant with a ≥75% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 75% responders during the Period/ number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment.


End point type 
Primary


End point timeframe 
Over 3month interval over the Evaluation Period (Month >5457)


Notes [20]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was done, as this is an open label study with only one treatment arm. Thus no statistical comparison is possible. 



No statistical analyses for this end point 


End point title 
Median partialonset seizure frequency per 28 days by 3month intervals over the Evaluation Period of the EP0073 study  
End point description 
Median partialonset seizure frequency per 28 days by 3month intervals over the Evaluation Period of the EP0073 study was reported. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, 'n' signifies participants who were evaluable at specified time points.


End point type 
Secondary


End point timeframe 
Over the 3month interval: Month 03, >36, >69, >912, >1215, >1518, >1821, >2124, >2427, >2730, >3033, >3336, >3639, >3942, >4245, >4548, >4851, >5154, >5457 over the Evaluation Period




No statistical analyses for this end point 


End point title 
Median partialonset seizure frequency per 28 days by seizure type by 3month intervals type over the Evaluation Period of the EP0073 study  
End point description 
Median partialonset seizure frequency per 28 days by seizure type (Type IA1, Type IB, Type IC) by 3month intervals over the Evaluation Period of the EP0073 study was reported. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, 'n' signifies participants who were evaluable at specified time points.


End point type 
Secondary


End point timeframe 
Over the 3month interval: Month 03, >36, >69, >912, >1215, >1518, >1821, >2124, >2427, >2730, >3033, >3336, >3639, >3942, >4245, >4548, >4851, >5154, >5457 over the Evaluation Period




No statistical analyses for this end point 


End point title 
Percent change in partialonset seizure frequency relative to the Baseline Period defined in EP0069 by 3month intervals over the Evaluation Period of the EP0073 study  
End point description 
Percent change from Baseline in seizure frequency for observable focalonset seizures (Type IA1, IB, and IC) to the corresponding interval was calculated using the following formula: change from Baseline in the 28 day adjusted seizure frequency/28 day adjusted seizure frequency during the EP0069 2 week Prospective Outpatient Baseline Period × 100. The numerator is calculated by subtracting the 28day adjusted seizure frequency during the Period of interest from the 28day adjusted seizure frequency during the EP0069 2week prospective outpatient Baseline Period. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment and 'n' signifies participants who were evaluable at specified time points.


End point type 
Secondary


End point timeframe 
Month 03, >36, >69, >912, >1215, >1518, >1821, >2124, >2427, >2730, >3033, >3336, >3639, >3942, >4245, >4548, >4851, >5154, >5457 over the Evaluation Period, Relative to Baseline (of EP0069)




No statistical analyses for this end point 


End point title 
50% responder rate by 3month intervals over the Evaluation Period of the EP0073 study  
End point description 
A 50% responder was defined as a participant with a ≥50% reduction in partialonset seizure (POS) frequency for observable focalonset seizures (Type IA1, IB, and IC) relative to the 2week Prospective Outpatient Baseline Period defined in EP0069. It was calculated using formula: Count of 50% responders during the Period/number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, number of participants analyzed included those participants who were evaluable for the assessment and 'n' signifies participants who were evaluable at specified time points.


End point type 
Secondary


End point timeframe 
Over the 3month interval: Month 03, >36, >69, >912, >1215, >1518, >1821, >2124, >2427, >2730, >3033, >3336, >3639, >3942, >4245, >4548, >4851, >5154, >5457 over the Evaluation Period




No statistical analyses for this end point 


End point title 
Percentage of seizurefree days by 3month intervals over the Evaluation Period  
End point description 
The number of seizurefree days is defined as the total number of days within an analysis Period or time interval for which no seizures were reported. The percentage of seizurefree days is to be computed as 100 times the number of seizurefree days divided by the number of days for which daily diary data was available in the specified analysis Period. Days without the corresponding daily diary data (ie, “Not Done” is ticked) are not used in these computations. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. Here, 'n' signifies participants who were evaluable at specified time points.


End point type 
Secondary


End point timeframe 
Over the 3month interval: Month 03, >36, >69, >912, >1215, >1518, >1821, >2124, >2427, >2730, >3033, >3336, >3639, >3942, >4245, >4548, >4851, >5154, >5457 over the Evaluation Period




No statistical analyses for this end point 


End point title 
Seizurefree rate over the Evaluation Period  
End point description 
Participants were considered seizure free for a given Period or time interval if the participant, completes the Period or time interval, reports no seizures during the Period, and has no more than 10% of days in the Period for which seizure data is not available (ie, “Not Done” is reported on the Seizure Count CRF). The seizure freedom rate (%) for a specific time Period will be calculated using the following formula: Count of seizure free participants during the Period/ Number of participants during the Period × 100. The FAS consisted of all enrolled study participants who took at least 1 dose of UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073.


End point type 
Secondary


End point timeframe 
Over the Evaluation Period (up to 5 years)




No statistical analyses for this end point 


End point title 
Changes in Quality of Life in Epilepsy 31P (QOLIE31P) total score from Visit 3 (Week 2) of EP0069 through the assessment of the Evaluation Period of EP0073  
End point description 
The QOLIE31P includes 30 items grouped into 7 multiitem subscales (seizure worry, overall quality of life, emotional wellbeing, energy/fatigue, cognitive functioning, medication effects, and social function) and a health status item. Individual responses for the 30 subscale items are rescaled to 0 to 100 with higher scores reflecting better functioning. Each subscale score is then calculated by summing rescaled responses for that subscale and dividing by number of items with nonmissing response. Responses for health status item are multiple of 10 ranging from 0 to 100 with higher score corresponding to better health status. The QOLIE31P total score was calculated as weighted sum of the subscale scores which ranges from 0 to 100 with higher score reflecting better functioning. FAS population was used. Here, number of participants analyzed included those participants who were evaluable for the assessment and ‘n’ signifies participants who were evaluable at specified time points.


End point type 
Secondary


End point timeframe 
Month 3, 7, 13, 19, 25, 31, 37, 43, 49, early discontinuation visit (EDV) (up to Month 58), Relative to Baseline (of EP0069)




No statistical analyses for this end point 


Adverse events information


Timeframe for reporting adverse events 
From Entry Visit to End of Safety FollowUp Visit (up to approximately 5 years)


Adverse event reporting additional description 
Treatmentemergent adverse events (TEAEs) were defined as adverse events (AEs) that started on or after the first dose of UCB0942 in EP0073 or AEs whose intensity worsened on or after the date of first dose of UCB0942 in EP0073.


Assessment type 
Nonsystematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
22.1


Reporting groups


Reporting group title 
UCB0942 (SS)


Reporting group description 
All enrolled participants continued the same UCB0942 dose which they were receiving during last visit of study EP0069 and the dose could be further increased or decreased in participants to optimize the drug tolerability and seizure control for each participant. Increases or decreases to the dose of UCB0942 was made in steps not exceeding 200 mg/day per week however, 800 mg/day to 500 mg/day change was allowed. Daily UCB0942 filmcoated tablets were administered orally in doses of 100 mg (50 mg bid), 200 mg (100 mg bid), 400 mg (200 mg bid), 600 mg (300 mg bid), or 800 mg (400 mg bid) for up to approximately 5 Years. Participants formed the Safety Set (SS).  


Frequency threshold for reporting nonserious adverse events: 5%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? Yes  
Date 
Amendment 

10 Dec 2015 
The following major changes were introduced in Protocol Amendment 1:
• A PSL 25mg tablet, which was previously unavailable, was introduced and a PSL maintenance dose of 100mg (50mg bid) was permitted to allow investigators to explore the range of doses from 100mg to 800mg per day using bid dosing.
• Pharmacokinetic (PK) blood samples for the measurement of plasma concentration of PSL and metabolites were added at several visits. These samples were taken to monitor study
participant compliance. Exploratory population PK analysis were performed together with evaluation of longerterm (up to 1 year) exposureresponse relationships.
• No tapering from the EP0069 dose before the first dose was administered in EP0073 was specified.
• If the study participant had active suicidal ideation with a specific plan as indicated by a positive response (“Yes”) to Question 5 of the “Since Last Visit” version of the ColumbiaSuicide Severity Rating Scale (CSSRS), the study participant was required to be referred immediately to a Mental Healthcare Professional and must have been withdrawn from the study. 

14 Nov 2016 
The following changes were introduced in Protocol Amendment 2:
• The protocol information pertaining to potential druginduced liver injury (PDILI) (exclusion criteria, withdrawal criteria, AEs of special interest, and assessment of safety) was updated
based on new standard language, which was applied across all protocols at UCB. Note that these additions did not reflect a change in the known safety of the compound. • The estimate of the approximate number of study participants from EP0069 who would be included in EP0073 was increased to approximately 40. • Additional contraceptive requirements for the partners of male study participants were removed (based on nonclinical data). 

09 Nov 2017 
The primary purpose of this substantial amendment was to change the frequency for the ECG assessments after Year 2. Of note, no study participants had reached this milestone at the time of this protocol amendment, and therefore no impact on the safety analysis was expected. In addition, following the annual revision of the investigator’s Brochure 2017 for PSL, the following prohibited concomitant medications were added in this protocol: strong CYP2C19 inhibitors, strong CYP2C19 inducers, and CYP2C19 sensitive substrates. As the recruitment for EP0073 had completed, study participants who were already taking these medications prior to Amendment 3, may have continued to do so, but under close monitoring.
The other major changes in this amendment were as follows:
• A study participant with a benefitrisk ratio of 0 to 4 (on a scale from 0 to 10) was required to be withdrawn from the study. • AEs of special interest were required to be immediately reported. • The Pharmacokinetic PerProtocol Set (PKPPS) that was used for the PK analysis was defined. 

Interruptions (globally) 

Were there any global interruptions to the trial? No  
Limitations and caveats 

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.  
None reported 