Clinical trial NCT02625090
Conditions: Highly Drug-resistant Focal Epilepsy
Keywords: Drug-resistance focal epilepsy partial-onset seizures
Sponsor: UCB Biopharma SRL
Start date: 2015-12-03; Completion date: 2020-11-24
Enrollment: 42 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of study EP0073 is to assess the long-term safety, tolerability, and efficacy during 5 years of treatment with the drug UCB0942 in patients with highly drug-resistant focal epilepsy. Also, the effects of UCB0942 on the patient's quality of life will be explored.

Detailed description:
For those subjects who benefit substantially from UCB0942 in the multicenter, randomized, double-blind, placebo-controlled, parallel group study EP0069, the current open-label extension study EP0073 will provide an opportunity to continue UCB0942 treatment after a careful evaluation of the individual benefit-risk balance and with close monitoring of safety, tolerability and efficacy of long-term study treatment.

Arms: arm 1: UCB0942 400 mg bid or a tapered UCB0942 dose of 200 mg bid.

The Investigator will be allowed to increase or decrease the dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or decreases to the dose of UCB0942 should be made in steps not exceeding 200 mg/day per week; an exception is Taper Week 1 where a step of 800 mg/day to 500 mg/day is allowed. A faster decrease of the dose than 200 mg/day per week is allowed when it is clinically appropriate in the Investigator's medical judgment. Daily UCB0942 doses during this study may be 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); intermediate doses will not be allowed except for tapering and titration unless agreed by the UCB Study Physician or PRA Medical Monitor. The dose of UCB0942 must always be administered as bid morning and evening doses, approximately 12 hours apart.
Interventions: intervention 1: UCB0942
Intervention descriptions: intervention 1: * Active Substance: UCB0942
* Pharmaceutical form: Film-coated tablet
* Concentration: 25 mg, 100 mg or 200 mg
* Route of Administration: oral

Protocol documents:
Prot_000.pdf: 
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PROTOCOL EP0073 AMENDMENT 3
AN OPEN-LABEL, MULTICENTER, EXTENSION STUDY TO 
EVALUATE THE LONG-TERM SAFETY, TOLERABILITY, AND 
EFFICACY OF UCB0942 WHEN USED AS ADJUNCTIVE 
THERAPY FOR PARTIAL-ONSET SEIZURES IN ADULT 
SUBJECTS WITH HIGHLY DRUG-RESISTANT FOCAL 
EPILEPSY
PHASE 2
EudraCT Number: 2015-001268-20
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
B-1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
11 Jun 2015
Not applicable
Protocol Amendment 1
10 Dec 2015
Substantial
Protocol Amendment 2
14 Nov 2016
Substantial
Protocol Amendment 3
09 Nov 2017
Substantial
Confidential Material
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
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STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL
Allée de la Recherche 60
B-1070 Brussels
BELGIUM
Coordinating Investigator
Name:
Prof. Dr. 
Affiliation:
University Hospital Ghent
Address:
De Pintelaan 185
9000 Ghent
BELGIUM
Phone:
Coordinating Investigator Germany
Name:
Prof. Dr. 
Affiliation:
Diakonie Kork
Address:
Landstraße 1
77694 Kehl-Kork
GERMANY
Phone:
Sponsor Study Physician
Name:
Prof. Dr.
Address:
UCB Biosciences GmbH
Alfred-Nobel-Straße 10
40789 Monheim
GERMANY
Phone:
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Clinical Project Manager
Name:
Address:
UCB Biosciences GmbH
Alfred-Nobel-Straße 10
40789 Monheim
GERMANY
Phone:
Fax:
Clinical Trial Biostatistician
Name:
Address:
UCB Pharma Ltd.
280 Bath Road
Berkshire SL 13WE Slough
UK
Phone:
Clinical Monitoring Contract Research Organization
Name:
PRA Health Sciences
Address:
4130 Parklake Avenue, Suite 400
Raleigh, NC 27612
USA
Phone:
+1 919 786 8200
Fax:
+1 919 786 8201
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SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
+32 2 386 24 21
Email
Global: DSICT@ucb.com
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TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................10
1
SUMMARY.....................................................................................................................13
2
INTRODUCTION ...........................................................................................................16
2.1
General background...............................................................................................16
2.2
Clinical experience.................................................................................................17
2.3
Risks and mitigation strategy.................................................................................18
2.3.1
Cardiac adverse events.................................................................................19
2.3.2
Psychiatric adverse events ...........................................................................19
2.3.3
Drug-drug interactions.................................................................................19
2.4
Rationale for this study..........................................................................................20
3
STUDY OBJECTIVE(S).................................................................................................20
3.1
Primary objective...................................................................................................20
3.2
Secondary objectives .............................................................................................20
3.3
Exploratory objective.............................................................................................20
4
STUDY VARIABLES.....................................................................................................21
4.1
Safety variables......................................................................................................21
4.1.1
Primary safety variable ................................................................................21
4.1.2
Other safety variables ..................................................................................21
4.2
Efficacy variables...................................................................................................21
4.2.1
Primary efficacy variable.............................................................................21
4.2.2
Secondary efficacy variables .......................................................................21
4.3
Exploratory pharmacokinetic variable...................................................................22
5
STUDY DESIGN.............................................................................................................22
5.1
Study description ...................................................................................................22
5.1.1
Study duration per subject ...........................................................................24
5.1.2
Planned number of subjects and sites ..........................................................25
5.1.3
Anticipated regions and countries................................................................25
5.2
Visit schedule.........................................................................................................25
5.3
Schedule of study assessments...............................................................................27
5.4
Rationale for study design and selection of dose...................................................32
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................32
6.1
Inclusion criteria ....................................................................................................32
6.2
Exclusion criteria ...................................................................................................33
6.3
Withdrawal criteria ................................................................................................34
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria................36
7
STUDY TREATMENT(S) ..............................................................................................38
7.1
Description of investigational medicinal product(s)..............................................38
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7.2
Treatments to be administered...............................................................................38
7.3
Packaging...............................................................................................................39
7.4
Labeling .................................................................................................................39
7.5
Handling and storage requirements .......................................................................39
7.6
Drug accountability................................................................................................40
7.7
Procedures for monitoring subject compliance......................................................40
7.8
Concomitant medication(s)/treatment(s) ...............................................................40
7.8.1
Permitted concomitant treatments (medications and therapies) ..................40
7.8.2
Prohibited concomitant treatments (medications and therapies) .................41
7.8.3
Rescue medication.......................................................................................41
7.9
Blinding..................................................................................................................41
7.10
Randomization and numbering of subjects............................................................41
8
STUDY PROCEDURES BY VISIT ...............................................................................42
8.1
Screening Period....................................................................................................42
8.2
Evaluation Period...................................................................................................42
8.2.1
Entry Visit....................................................................................................42
8.2.2
Telephone Calls ...........................................................................................43
8.2.3
Minimal Evaluation Visit.............................................................................43
8.2.4
Full Evaluation Visit....................................................................................44
8.2.5
Yearly Evaluation Visit and Early Discontinuation Visit............................44
8.3
Taper Period...........................................................................................................45
8.4
Safety Follow-Up Period .......................................................................................46
8.4.1
Safety Follow-Up Visit 1.............................................................................46
8.4.2
Safety Follow-Up Visit 2.............................................................................46
8.5
Unscheduled Visit/Telephone Contact ..................................................................47
9
ASSESSMENT OF EFFICACY......................................................................................47
9.1
Seizure frequency...................................................................................................47
9.2
Quality of Life Inventory in Epilepsy-31-P...........................................................48
10
ASSESSMENT OF PHARMACOKINETICS................................................................48
10.1
Sampling procedures..............................................................................................48
10.2
Bioanalytical methods............................................................................................48
11
ASSESSMENT OF SAFETY..........................................................................................49
11.1
Adverse events.......................................................................................................49
11.1.1
Definition of adverse event..........................................................................49
11.1.2
Procedures for reporting and recording adverse events...............................49
11.1.3
Description of adverse events......................................................................49
11.1.4
Follow up of adverse events ........................................................................49
11.1.5
Rule for repetition of an adverse event........................................................50
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11.1.6
Pregnancy.....................................................................................................50
11.1.7
Overdose of investigational medicinal product ...........................................51
11.1.8
Safety signal detection.................................................................................51
11.2
Serious adverse events...........................................................................................52
11.2.1
Definition of serious adverse event .............................................................52
11.2.2
Procedures for reporting serious adverse events..........................................53
11.2.3
Follow up of serious adverse events............................................................53
11.3
Adverse events of special interest..........................................................................53
11.4
Immediate reporting of adverse events..................................................................54
11.5
Anticipated serious adverse events........................................................................54
11.6
Laboratory measurements......................................................................................54
11.6.1
Evaluation of PDILI.....................................................................................55
11.6.1.1
Consultation with the Medical Monitor and local hepatologist.........59
11.6.1.2
Immediate action: determination of IMP discontinuation .................59
11.6.1.3
Testing: identification/exclusion of alternative etiology ...................60
11.6.1.4
Follow-up evaluation .........................................................................61
11.7
Other safety measurements....................................................................................61
11.7.1
Vital signs ....................................................................................................61
11.7.2
Electrocardiogram........................................................................................62
11.7.3
Echocardiogram...........................................................................................62
11.7.4
Physical and neurological examination .......................................................62
11.7.5
Assessment of suicidality.............................................................................63
11.7.6
Psychiatric and cognitive assessments.........................................................63
11.7.7
Monitoring symptoms of withdrawal ..........................................................63
11.7.8
Narratives of benefit and benefit-risk assessment .......................................63
12
STUDY MANAGEMENT AND ADMINISTRATION.................................................64
12.1
Adherence to protocol............................................................................................64
12.2
Monitoring .............................................................................................................64
12.2.1
Definition of source data..............................................................................64
12.2.2
Source data verification ...............................................................................65
12.3
Data handling.........................................................................................................65
12.3.1
Case Report form completion......................................................................65
12.3.2
Database entry and reconciliation................................................................65
12.3.3
Subject Screening and Enrollment log/Subject Identification Code list......65
12.4
Termination of the study........................................................................................66
12.5
Archiving and data retention..................................................................................66
12.6
Audit and inspection ..............................................................................................66
12.7
Good Clinical Practice...........................................................................................67
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13
STATISTICS ...................................................................................................................67
13.1
Definition of analysis sets......................................................................................67
13.2
General statistical considerations...........................................................................67
13.3
Planned safety analyses..........................................................................................67
13.4
Planned efficacy analyses ......................................................................................68
13.4.1
Analysis of the primary efficacy variable....................................................68
13.4.2
Analysis of the secondary efficacy variables...............................................68
13.5
Planned pharmacokinetic analyses ........................................................................68
13.6
Handling of protocol deviations.............................................................................69
13.7
Handling of dropouts or missing data....................................................................69
13.8
Planned interim analysis and data monitoring.......................................................69
13.9
Determination of sample size.................................................................................70
14
ETHICS AND REGULATORY REQUIREMENTS......................................................70
14.1
Informed consent ...................................................................................................70
14.2
Subject identification cards....................................................................................70
14.3
Independent Ethics Committees ............................................................................70
14.4
Subject privacy.......................................................................................................71
14.5
Protocol amendments.............................................................................................71
15
FINANCE, INSURANCE, AND PUBLICATION.........................................................72
16
REFERENCES ................................................................................................................73
17
APPENDICES .................................................................................................................75
17.1
Protocol Amendment 1 ..........................................................................................75
17.2
Protocol Amendment 2 ..........................................................................................87
17.3
Protocol Amendment 3 ........................................................................................108
18
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................126
19
DECLARATION AND SIGNATURE OF COORDINATING INVESTIGATOR 
(GERMANY).................................................................................................................127
20
DECLARATION AND SIGNATURE OF COORDINATING INVESTIGATOR......128
21
SPONSOR DECLARATION ........................................................................................129
LIST OF TABLES
Table 5‒1: Study visit schedule..............................................................................................25
Table 5‒2: Schedule of study assessments .............................................................................28
Table 7‒1: Three-week taper schedule for UCB0942 ............................................................38
Table 11‒1:
Anticipated SAEs for the epilepsy population.............................................54
Table 11‒2:
Laboratory measurements............................................................................54
Table 11‒3:
Required investigations and follow up for PDILI .......................................57
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Table 11‒4:
PDILI laboratory measurements..................................................................60
Table 11‒5:
PDILI information to be collected...............................................................61
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LIST OF ABBREVIATIONS
50%RR
50% responder rate
75%RR
75% responder rate
AE
adverse event
AED
antiepileptic drug
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
bid
twice daily
BP
blood pressure
BPRS
Brief Psychiatric Rating Scale
BRV
brivaracetam
cBZR
benzodiazepine-binding site
CDMS
clinical data management system
CIWA-B
Clinical Institute Withdrawal Assessment-Benzodiazepines
CMR
cardiac magnetic resonance
CNS
central nervous system
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CRO
contract research organization
C-SSRS
Columbia-Suicide Severity Rating Scale
CYP
cytochrome P450
DDI
drug-drug interaction(s)
DMC
Data Monitoring Committee
ECG
electrocardiogram
eCRF
electronic Case Report form
EDV
Early Discontinuation Visit
EMA/EMEA
European Medicines Agency
EudraCT
European Union Drug Regulating Authorities Clinical Trials
EV
Entry Visit
FAS
Full Analysis Set
FEV
Full Evaluation Visit
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FV
Final Visit
GABA-A
gamma-aminobutyric acid receptor type A
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IMP
investigational medicinal product
IRT
interactive response technology
LEPV
Last Evaluation Period Visit
LEV
levetiracetam
M
Month
MedDRA
Medical Dictionary for Regulatory Activities
MEV
Minimal Evaluation Visit
MMSE
Mini-Mental State Examination
OLE
open-label extension
PDILI
potential drug-induced liver injury 
PK
pharmacokinetic(s)
POS
partial-onset seizure
PS
Patient Safety
QOLIE-31-P
Quality of Life Inventory in Epilepsy-31-P
QTcB
QT corrected for heart rate using Bazett’s formula
QTcF
QT corrected for heart rate using Fridericia’s formula
RR
respiratory rate
SAE
serious adverse event
SAP
Statistical Analysis Plan
SFU
Safety Follow-Up
SOC
System Organ Class
SOP
Standard Operating Procedure
SS
Safety Set
SV2
synaptic vesicle glycoprotein 2
TC
Telephone Call
TEAE
treatment-emergent adverse event
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ULN
upper limit of normal
V
Visit
VNS
vagus nerve stimulation
Wk
Week
YEV
Yearly Evaluation Visit
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1
SUMMARY
UCB0942 is a new chemical entity with selective affinity for synaptic vesicle glycoprotein 2 
(SV2) and for the benzodiazepine-binding site (cBZR) on the gamma-aminobutyric acid receptor 
type A (GABA-A). UCB0942 has shown superior efficacy in several preclinical models of 
epilepsy.
EP0073 is an open-label extension (OLE) study that will run throughout the clinical development 
period of UCB0942 and will continue for approximately 5 years or until either a marketing 
authorization is granted by any health authority for the adjunctive treatment for partial-onset 
seizures (POS) in adult subjects with highly drug-resistant focal epilepsy, or until UCB decides 
to close the study.
Subjects who experience substantial benefit from UCB0942 with acceptable tolerability in 
EP0069 may have the opportunity to continue UCB0942 treatment in this OLE study. The 
decision to enter this study must be made by the Investigator in consultation with the subject and 
his/her caregiver. The Investigator’s decision must take into account the benefit experienced and 
the potential risks of long-term exposure to UCB0942, as well as the potential benefit and risks 
of other treatment options available. 
A Data Monitoring Committee (DMC) will systematically monitor and report on the progress, 
safety, and/or critical efficacy endpoints of the study. This includes evaluating the safety signals 
and benefit-risk balance for the study subjects in relationship to new data relevant for the 
efficacy and safety of the investigational medicinal product (IMP). The benefit-risk balance of 
every subject entering the study will be reviewed by the DMC within approximately 3 months 
after first dosing in EP0073. Voting members of the DMC will include external physicians with 
experience in treating refractory epilepsy and a cardiologist. The DMC will make 
recommendations to the company about continuation of the study, which may include changes to 
study procedures, or termination of the clinical study.
The study will consist of:

A 2-week Screening Period from Visit 13 (V13) to V15 (Days OP43 to OP57) of the 8-week 
Outpatient Maintenance Period of the EP0069 study. The Screening Visit will be on V13 of 
EP0069 and will be V1 of the current OLE study. At this visit, informed consent will be 
signed and inclusion and exclusion criteria (from the current OLE study) will be checked.
The verbatim of the attained benefits of treatment with UCB0942, including seizure control, 
health and well-being, and social functioning, declared by a subject/caregiver will be 
captured as narratives and filled in by the Investigator or site personnel. During the Screening 
Period, the Investigator will also provide a statement and a brief justification of the
benefit-risk balance for each subject’s participation in EP0073 and long-term treatment with 
UCB0942. These narratives of benefit by the subject/caregiver and the benefit-risk statement 
and the justification by the Investigator will be maintained as source documents and will be 
reviewed by the DMC. 

An Evaluation Period of up to approximately 5 years, which will start with V2, the Entry 
Visit (EV), which is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance 
Period of EP0069. Eligible subjects will enter EP0073 before the planned dose tapering in 
EP0069. Subjects will be issued and return seizure diaries during each visit. Subjects must be 
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educated to record all types of seizures that occur, any illness or injury, and all study 
medication intake in their seizure diary and be educated to complete their diary entries after 
each seizure or at least once a day. Throughout the study, the Investigator also will be 
requested to periodically re-assess and re-confirm that the benefit-risk ratio for the subject on
long-term treatment with the IMP, considering the knowledge of the IMP’s efficacy and 
safety profile and alternative treatment options, justifies continuation in the study. Narratives 
of benefit by the subject/caregiver and the benefit-risk statement and the justification by the
Investigator will be captured in a dedicated form at the scheduled time points presented in 
Table 5‒2.
First year:
In the first month of EP0073, subjects will have Telephone Calls (TCs) (Month [M]1-Week 
[Wk]1 [TC1] and M1-Wk3 [TC2]) and 1 clinic visit (M1-Wk2 [V3]). During the 2 TCs, the 
site personnel will review changes in concomitant medications (including antiepileptic drugs 
[AEDs]), confirm whether the subject experienced any adverse events (AEs)/serious adverse 
events (SAEs), and ensure that subjects are compliant with their study medication dosing 
schedule as outlined in the protocol. 
During the second, third and fourth months, subjects will visit the clinic at M2 (V4, Minimal 
Evaluation Visit [MEV]), M3 (V5, Full Evaluation Visit [FEV]), and M4 (V6, MEV).
Subjects will return to the clinic every 3 months for the remainder of the first year with FEV 
alternating with MEV: M7 (V7, FEV) and M10 (V8, MEV).
Second and third year:
For the second and third years, subjects will have clinic visits every 3 months, with MEVs 
alternating with FEVs/Yearly Evaluation Visits (YEVs), beginning with M13 (V9, YEV).
Fourth and fifth year:

For subjects who continue to participate in EP0073 beyond the 3-year period, the subjects 
will have a clinic visit every 6 months with YEVs alternating FEVs.

A Taper Period starting at the Last Evaluation Period Visit (LEPV) of the Evaluation Period; 
during the Taper Period, subjects will start to gradually decrease their dose of UCB0942. The 
Taper Period is planned to be 3 weeks, however a faster taper schedule than the suggested 
3 weeks may be implemented if medically necessary. A slower taper schedule of up to 
6 weeks may be implemented as per the Investigator’s medical judgment. 

A Safety Follow-Up (SFU) Period; subjects must return to the clinic 1 week after 
administration of the final dose of UCB0942 (SFU1). A Final Visit (FV) will be scheduled 
30 days after administration of the final dose of UCB0942 (SFU2).
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP0069. They will continue this dose in the current study and there will be no 
tapering from the EP0069 dose before they receive the first dose in EP0073; however,
throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
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decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
twice daily [bid]), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration. Exceptions 
may be allowed after consultation with the PRA Medical Monitor. The dose of UCB0942 must 
always be administered as bid morning and evening doses, approximately 12 hours apart. The 
first dose of the current study will be the dose on the evening of V2.
Concomitant AEDs and AED dose(s), or vagus nerve stimulation (VNS) settings may be
adjusted throughout EP0073 as per the Investigator’s clinical judgment based on tolerability and 
seizure control for each individual subject.
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. New concomitant AEDs may be introduced to optimize 
tolerability and seizure reduction.
If at any time the subject and/or the Investigator decide to discontinue UCB0942, the subject 
should return for an Early Discontinuation Visit (EDV) and gradually decrease their dose of 
UCB0942.
For each subject, the study will last from study entry for approximately 5 years or until either 
regulatory approval of UCB0942 has been granted by any health authority for the adjunctive 
treatment for POS in adult subjects with highly drug-resistant focal epilepsy, or until UCB 
decides to close the study.
The primary objective of this study is to evaluate the long-term safety and tolerability of 
UCB0942 at individualized doses between 100mg/day to a maximum of 800mg/day in subjects 
with highly drug-resistant focal epilepsy. The secondary objectives are to evaluate the long-term 
efficacy of UCB0942 and to evaluate the effects of UCB0942 on the subject’s quality of life
using the Quality of Life Inventory in Epilepsy-31-P (QOLIE-31-P; Cramer et al, 2003). The 
exploratory objective is to evaluate the plasma concentrations of UCB0942 and metabolites.
The primary safety variable is the occurrence of AEs reported by the subject and/or caregiver or 
observed by the Investigator or clinical site staff beginning at the EV of the Evaluation Period
during the EP0073 study.
Other safety variables are:

Changes from EP0069 baseline  in laboratory tests (including hematology, blood chemistry, 
urinalysis) at each assessment during the EP0073 study 

Changes from EP0069 baseline in 12-lead electrocardiogram (ECG) parameters at each 
assessment during the EP0073 study

Changes from EP0069 baseline in psychiatric assessments as assessed with the Brief 
Psychiatric Rating Scale (BPRS; Overall and Gorham, 1962) at each assessment during the 
EP0073 study

Changes from EP0069 baseline in memory or cognition as assessed with the Mini-Mental 
State Examination (MMSE; Folstein et al, 1975) at each assessment during the EP0073 study
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
Changes in withdrawal symptoms using the Clinical Institute Withdrawal Assessment-
Benzodiazepines (CIWA-B; Busto et al, 1989) from the LEPV (last visit prior to Taper
Period), at each assessment during the Taper Period (visit at the end of the Taper Period) and 
during the SFU Period (visits at 1 week and 30 days after administration of the final dose of 
UCB0942) of the EP0073 study

Changes from EP0069 baseline in vital sign parameters (pulse rate, blood pressure [BP], and 
respiratory rate [RR]) at each assessment during the EP0073 study

Occurrence of a clinically concerning valvular or pericardial effusion change or other 
clinically significant abnormalities as identified by 2-dimensional Doppler echocardiography 
at each assessment during the EP0073 study

Changes from EP0069 baseline in physical examination (including body weight) and 
neurological examination findings at each assessment during the EP0073 study.
With regard to efficacy, in both this study and EP0069 only POS of type IA1, IB, and IC and not 
non-motor IA2, IA3 or IA4 seizures will be counted for the assessment of seizure frequency and 
responder rate. For assessment of seizure-free rate and days, all seizure types will be considered.
The primary efficacy variable is the 75% responder rate (75%RR) by 3-month intervals over the 
Evaluation Period. A 75% responder is defined as a subject with a ≥75% reduction in POS 
frequency relative to the 2-week Prospective Outpatient Baseline Period defined in EP0069.
Secondary efficacy variables are described in Section 4.2.2 and the exploratory pharmacokinetic 
(PK) variable is described in Section 4.3.
2
INTRODUCTION
2.1
General background
In Europe and North America, there are approximately 350 to 500 thousand (3 to 4 million 
worldwide) patients with focal epilepsy who have not been able to achieve freedom from 
disabling seizures despite sequential and/or combination treatment with several of the available 
AEDs. Even with the introduction of 12 new AEDs over the last 2 decades, the proportion of 
patients with epilepsy who are unable to achieve complete control of their seizures has only 
decreased minimally, from 36% to 34% (Brodie et al, 2012), highlighting this large unmet 
medical need and the fact that recently developed AEDs have not been able to meet this medical 
need.
The likelihood of achieving complete seizure control diminishes further as the number of failed 
AEDs regimens increases. Thus, when a patient with focal epilepsy has not been able to control 
their seizures despite treatment with 4 or more AED regimens, the likelihood of achieving 
complete seizure control with another AED regimen is 1% to 4% (Schiller and Najjar, 2008; 
Mohanraj and Brodie, 2006; UCB internal data on lacosamide and brivaracetam [BRV]). This 
group of patients, who are the target population for this study, will be referred to as having 
“highly drug-resistant focal epilepsy.”
Although resective surgery is an option for some patients with drug-resistant focal epilepsy, 
fewer than 1% of patients with drug-resistant focal epilepsy are evaluated for epilepsy surgery 
due to various factors (limited number of epilepsy surgery centers, lack of referral, inability to 
localize the seizure focus during work-up, contraindications to surgery, etc.; Engel, 2013). 
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Therefore, the vast majority of patients with highly drug-resistant focal epilepsy have no 
treatment options (pharmacological or surgical) that can provide complete seizure control or 
even substantial reduction in the number of seizures.
In patients with uncontrolled focal epilepsy, seizures increase the risk of mortality and have a 
negative impact on psychosocial functioning and quality of life across multiple dimensions. 
Patients with drug-resistant focal epilepsy and complex-partial or tonic-clonic seizures have 5 to 
10 times higher mortality rate (Fazel et al, 2013; Hesdorffer and Tomson, 2013; Holst et al, 
2013; Sperling, 2004) including risk of sudden unexplained death in epilepsy (Devinsky, 2011). 
Moreover, drug-resistant focal epilepsy is regarded by many experts as a progressive disease in 
which ongoing seizures result in an increased risk of further seizures. These patients are prone to 
falls and injuries; they cannot drive and can rarely live independently; they feel isolated and 
stigmatized; they have difficulty finding and keeping a job and often depend on disability 
benefits (Azuma and Akechi, 2014; Taylor et al, 2001; Baker et al, 1997). A treatment that 
provides seizure freedom will reduce mortality (Laxer et al, 2014) and significantly improve 
quality of life (Choi et al, 2014; Baker et al, 1997) by increasing their ability to attain basic 
safety, freedom from the risk of falls and injuries, and reach the milestones that most people take 
for granted: a feeling of belonging and social integration, the ability to form intimate 
relationships and a family, and having a productive and rewarding profession or other means of 
self-realization.
UCB0942 has shown superior efficacy in several preclinical models of epilepsy. UCB0942 is 
superior to levetiracetam (LEV) and BRV in 10 animal models of focal and generalized epilepsy, 
indicating that it has broad antiseizure effects. In the rat amygdala kindling model – a model of 
drug-resistant focal epilepsy – UCB0942 is superior to 12 other AEDs tested thus far: LEV, 
BRV, phenytoin, phenobarbital, carbamazepine, lacosamide, valproate, retigabine, perampanel, 
clobazam, diazepam, clonazepam, and the combination of LEV or BRV with diazepam. In this 
model of drug-resistant focal epilepsy, UCB0942 was the only compound that produced 
complete seizure suppression in all animals at a plasma exposure equivalent to the plasma 
exposure achieved in humans taking UCB0942 400mg bid. Other AEDs produced seizure 
suppression in this model, but only at plasma exposures that are unattainable in humans. 
Based on its superior preclinical efficacy profile, UCB0942 may show efficacy in patients with 
focal epilepsy who continue to suffer from frequent seizures despite having attempted to achieve 
seizure control with multiple AED regimens (patients with highly drug-resistant focal epilepsy).
If seizure freedom or a substantial reduction in seizure frequency could be achieved in these 
patients, their quality of life would dramatically improve, and this improvement is expected to 
outweigh the potential risks associated with the administration of UCB0942.
Preclinical experience with UCB0942 is described extensively in the Investigator’s Brochure.
2.2
Clinical experience
UCB0942 has completed Phase 1 development with a total of 145 subjects exposed to single 
doses up to UCB0942 490mg and multiple doses up to UCB0942 400mg bid for up to 14 days, 
including 20 subjects with epilepsy at 400mg bid. There were no clinically significant changes in 
laboratory tests or vital signs thought to be related to UCB0942 during Phase 1 development, 
although transient, minor reductions in systolic and diastolic BP were seen (consistent with the 
known effects of benzodiazepine drugs). There were no clinically significant changes attributed 
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to UCB0942 in 12-lead ECGs; however, 4 subjects had treatment-emergent rhythm disturbances 
(atrial and ventricular ectopy). These were asymptomatic and were assessed by an external 
expert in cardiology and electrophysiology as unlikely to be related to UCB0942.
The safety findings to date suggest that the AE profile in subjects receiving single and repeated 
doses of UCB0942 is defined mostly by central nervous system (CNS) effects. At UCB0942 
300mg bid and above the AEs tend to be of slightly greater severity and persistence than at doses 
below 300mg bid. In broad terms, the AEs are consistent with the safety profiles of SV2A and 
GABA-A targeting AEDs, and common CNS AEs include headache, nausea, somnolence, 
fatigue, dizziness, balance disorder, disturbance in attention, and memory impairment. Modeling 
of the relationship between dose or plasma exposure, time, and AEs showed that 1) headache, 
fatigue, somnolence, balance disorder, and disturbance in attention are dose-dependent AEs; 2) 
tolerance develops for disturbance in attention and balance disorder; 3) tolerance does not seem 
to develop for fatigue, somnolence, and headache; and 4) titration will reduce the likelihood that 
a subject experiences most of these AEs.
2.3
Risks and mitigation strategy
The important identified risks based on clinical data include the development of acute psychiatric 
effects and drug-drug interactions (DDIs) with strong cytochrome P450 (CYP) 3A4 enzyme 
inducers leading to decreased exposure levels of UCB0942. There are also some important 
potential risks that are UCB0942-specific based on clinical data, including impairment of 
cognitive and psychomotor performance, DDI between UCB0942 with CYP2C19 substrates 
leading to increased levels of these substrates, and decrease in blood pressure. In addition, there 
are several potential risks for UCB0942 that are class effects or known for other products, 
including suicidality, worsening of seizures, substance abuse and dependence, tolerance to the 
anticonvulsant effects of the drug, and decreased bone mineral density. Finally, there are a 
number of potential risks that are UCB0942-specific based on nonclinical data, including
epicardial and valvular inflammation and epicardial fibroplasia with administration longer than 
13 weeks, QT prolongation, hepatoxicity, DDI with strong CYP3A4 inhibitors leading to 
increased exposure levels of UCB0942, DDI with strong CYP2C19 inhibitors or inducers 
leading to increased or decreased exposure levels of UCB0942, and growth retardation.
All identified and potential risks, with the exception of decreased growth (applicable only to 
pediatric studies) will be appropriately mitigated in the proposed clinical study. Clinical data 
from the completed study EP0069 have been reviewed by a DMC that included internal UCB 
and external medical experts. Data from this study and any other relevant data that become
available (such as preclinical data) will be reviewed by the DMC in order to detect and 
characterize as early as possible any concern(s) related to UCB0942 (see Section 11.1.8).
Investigators, clinical study subjects, regulatory authorities, and Institutional Review 
Boards/Independent Ethics Committees (IECs) will be informed in a timely manner of any 
significant information that affects the benefit-risk balance of the UCB0942 and participation in 
the study. The specific mitigation measures for cardiac AEs, psychiatric events and drug-drug 
interactions are discussed further below, and additional details about risks and mitigation 
strategy are provided in Section 6 of the Investigator’s Brochure.
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2.3.1
Cardiac adverse events
In the 39-week dog toxicology study, subtle cardiac microscopic findings were observed, 
consisting of minimal inflammatory cell infiltration in the aortic and mitral valves (in 3 out of 
24 dogs) and minimal to slight epithelial inflammation (fibroplasia) in the right atrial epicardium 
(in 5 out of 24 dogs). The epicardial findings were active (ie, there is a potential for progression), 
while the valvular findings were not active. The histopathology in the 39-week dog study was 
reviewed by 4 pathologists, including one who is an expert in cardiac pathology, and they 
concluded that the findings were subtle and not adverse for the dogs. A cardiologist concluded 
that the potential cardiac hazard of UCB0942 in humans is likely minimal; however, it is 
possible that epicardial or valvular structural changes will occur in humans with prolonged 
exposure (beyond 3 months).
Therefore, in this study, subjects will have an echocardiogram at Visit 2 and every 3 months for 
the first year and second year of treatment, and every 6 months in subsequent years to ensure 
early detection of any valvular or pericardial changes that may occur.
2.3.2
Psychiatric adverse events
In the course of UCB0942 development, 3 psychiatric SAEs (delirious syndrome, mania-like 
symptoms, and acute psychosis) have been reported in 2 healthy volunteers and 1 patient with 
resistant epilepsy, respectively. The events were transient, acute, and required admission to 
psychiatric care and antipsychotics. The events in healthy subjects occurred early after initiation 
of UCB0942, which was done without titration. In 1 of the subjects symptoms worsened upon 
abrupt drug discontinuation. The psychotic effect in the epilepsy subject emerged after dramatic 
improvement in seizures control and electroencephalographic activity a few weeks after start of 
UCB0942, suggesting “forced normalization” (Loganathan et al, 2015; Clemens, 2005). Dose 
reduction of UCB0942 and neuroleptic treatment resulted in complete resolution of psychosis 
within days, as the treatment with UCB0942 continued. 
In the current study, subjects will have a psychiatric (BPRS) and cognitive (MMSE) assessment 
at study visits every 3 months for years 1, 2 and 3, and every 6 months for years 4 and 5. The 
CIWA-B will be performed at the LEPV (last visit prior to the Taper Period)/EDV, at the visit at 
the end of the Taper Period) and at SFU1 and SFU2 (1 week and 30 days after administration of 
the final dose of UCB0942, respectively). In addition, to further reduce the risk that participating 
subjects develop psychiatric AEs, subjects with a history of psychosis, schizophrenia, bipolar 
disorder, or severe unipolar depression will be excluded from this study. Lastly, based on the fact 
that titration has been shown to reduce the incidence of other AEs and increase the general 
tolerability of UCB0942, titration may also reduce the risk of psychiatric AEs.
2.3.3
Drug-drug interactions
A drug-drug interaction study in subjects with epilepsy showed that carbamazepine – a strong 
CYP3A4 inducer – reduced UCB0942 plasma exposure by >85%. Therefore, subjects on 
carbamazepine or other strong CYP3A4 inducers (eg, phenytoin, phenobarbital, or primidone) 
will not be enrolled in this study because the plasma exposure may be too low to produce any 
therapeutic benefit.
Preclinical data indicate the potential involvement of CYP2C19 in the metabolism of 
UCB0942.While the contribution of CYP2C19 is still unclear regarding the degree to which it 
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contributes to the metabolism of UCB0942 or its metabolites, both strong inhibitors and inducers 
of CYP2C19 will also be prohibited. Additionally, in studies with human study participants, 
drug-drug interaction of UCB0942 (perpetrator) with CYP2C19 substrates (victims) was 
observed leading to increased levels of CYP2C19 substrates. Therefore, concomitant use of 
sensitive CYP2C19 substrates will be prohibited in EP0073. If subjects are already taking strong 
inducers or inhibitors or sensitive substrates of CYP2C19 prior to Amendment 3, they may 
continue to do so, but close monitoring should be implemented.
2.4
Rationale for this study
UCB believes that, based on the evidence of unprecedented superiority to other marketed AEDs 
across several preclinical models of epilepsy, UCB0942 may be of potential benefit with an 
acceptable risk/benefit profile in a high unmet medical need patient population, namely those 
who have highly drug-resistant focal epilepsy whose uncontrolled seizures constitute a 
substantial threat to their health and well-being. 
The EP0069 multicenter, randomized, double-blind placebo-controlled, parallel-group study will 
make the first assessment of the safety and efficacy of UCB0942 in the adjunctive treatment of 
POS with or without secondary generalization in subjects with highly drug-resistant epilepsy 
despite optimal medical AED treatment.
For those subjects who benefit substantially from UCB0942 in EP0069, the current OLE study 
will provide an opportunity to continue UCB0942 treatment after a careful evaluation of the 
individual benefit-risk balance and with close monitoring of safety, tolerability and efficacy of 
long-term study treatment. As such, the purpose of the current study, EP0073, is to assess the 
long-term safety, tolerability, and efficacy associated with oral UCB0942 in subjects with highly 
drug-resistant focal epilepsy. Also, the effects of UCB0942 on the subject’s quality of life will be 
explored.
3
STUDY OBJECTIVE(S)
3.1
Primary objective

To evaluate the long-term safety and tolerability of UCB0942 at individualized doses 
between 100mg/day to a maximum of 800mg/day in subjects with highly drug-resistant focal 
epilepsy.
3.2
Secondary objectives

To evaluate the long-term efficacy of UCB0942

To evaluate the effects of UCB0942 on the subject’s quality of life.
3.3
Exploratory objective

To evaluate the plasma concentrations of UCB0942 and metabolites.
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4
STUDY VARIABLES
4.1
Safety variables
4.1.1
Primary safety variable

Occurrence of AEs reported by the subject and/or caregiver or observed by the Investigator 
or clinical site staff beginning at the EV of the Evaluation Period during the EP0073 study
4.1.2
Other safety variables

Changes from EP0069 baseline  in laboratory tests (including hematology, blood chemistry, 
urinalysis) at each assessment during the EP0073 study

Changes from EP0069 baseline in 12-lead ECG parameters at each assessment during the 
EP0073 study

Changes from EP0069 baseline in psychiatric assessments as assessed with the BPRS at each 
assessment during the EP0073 study

Changes from EP0069 baseline in memory or cognition as assessed with the MMSE at each 
assessment during the EP0073 study

Changes in withdrawal symptoms using CIWA-B from the LEPV (last visit prior to the 
Taper Period), at each assessment during the Taper Period (visit at the end of the Taper 
Period) and during the SFU Period (visits at 1 week and 30 days after administration of the 
final dose of UCB0942) of the EP0073 study 

Changes from EP0069 baseline in vital sign parameters (pulse rate, BP, and RR) at each 
assessment during the EP0073 study

Occurrence of a clinically concerning valvular or pericardial effusion change or other 
clinically significant abnormalities as identified by 2-dimensional Doppler echocardiography 
at each assessment during the EP0073 study

Changes from EP0069 baseline in physical examination (including body weight) and 
neurological examination findings at each assessment during the EP0073 study
4.2
Efficacy variables
In both this study and EP0069 only POS of type IA1, IB, and IC and not non-motor IA2, IA3 or 
IA4 seizures will be counted for the assessment of seizure frequency and responder rate. For 
assessment of seizure-free rate and days, all seizure types will be considered.
4.2.1
Primary efficacy variable

The primary efficacy variable is the 75%RR by 3-month intervals over the Evaluation Period. 
A 75% responder is defined as a subject with a ≥75% reduction in POS frequency relative to 
the 2-week Prospective Outpatient Baseline Period defined in EP0069.
4.2.2
Secondary efficacy variables

Median POS frequency per 28 days by 3-month intervals over the Evaluation Period of the 
EP0073 study.
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
Median POS frequency per 28 days by seizure type by 3-month intervals over the Evaluation 
Period of the EP0073 study.

Percent reduction in POS frequency relative to the 2-week Prospective Outpatient Baseline 
Period defined in EP0069 by 3-month intervals over the Evaluation Period of the EP0073 
study.

The 50% responder rate (50%) RR by 3-month intervals over the Evaluation Period of the 
EP0073 study. A 50% responder is defined as a subject with a ≥50% reduction in POS 
frequency relative to the 2-week Prospective Outpatient Baseline Period defined in EP0069.

Percentage of seizure-free days by 3-month intervals over the Evaluation Period.

Seizure-free rate by 3-month intervals over the Evaluation Period.

Changes in QOLIE-31-P scores from V3 of EP0069 through the assessment of the 
Evaluation Period.
4.3
Exploratory pharmacokinetic variable

Plasma concentrations of UCB0942 and metabolites during the first 13 months of treatment 
in EP0073. 
5
STUDY DESIGN
5.1
Study description
This is an OLE study that will run throughout the clinical development period of UCB0942 and 
will continue for approximately 5 years or until either until a marketing authorization is granted 
by any health authority for the adjunctive treatment for POS in adult subjects with highly 
drug-resistant focal epilepsy, or until UCB decides to close the study.
Subjects who experience substantial benefit from UCB0942 with acceptable tolerability in 
EP0069 may have the opportunity to continue UCB0942 treatment in this OLE study. The 
decision to enter this study must be made by the Investigator in consultation with the subject and 
his/her caregiver. The Investigator’s decision must take into account the benefit experienced and 
the potential risks of long-term exposure to UCB0942, as well as the potential benefit and risks 
of other treatment options available. 
A DMC will systematically monitor and report on the progress, safety, and/or critical efficacy 
endpoints of the study. This includes evaluating the safety signals and benefit-risk balance for 
the study subjects in relationship to new data relevant for the efficacy and safety of the IMP. The 
benefit-risk balance of every subject entering the study will be reviewed by the DMC within 
approximately 3 months after first dosing in EP0073. Voting members of the DMC will include 
external physicians with experience in treating refractory epilepsy and a cardiologist. The DMC 
will make recommendations to the company about continuation of the study, which may include 
changes to study procedures, or termination of the clinical study.
The study will consist of:

A 2-week Screening Period from V13 to V15 (Days OP43 to OP57) of the 8-week Outpatient 
Maintenance Period of the EP0069 study. The Screening Visit will be on V13 of EP0069 and 
will be V1 of the current OLE study. At this visit, informed consent will be signed and 
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inclusion and exclusion criteria (from the current OLE study) will be checked. The verbatim 
of the attained benefits of treatment with UCB0942, including seizure control, health and 
well-being, and social functioning, declared by a subject/caregiver will be captured as 
narratives and filled in by the Investigator or site personnel. During the Screening Period, the 
Investigator will also provide a statement and a brief justification of the benefit-risk balance 
for each subject’s participation in EP0073 and long-term treatment with UCB0942. These 
narratives of benefit by the subject/caregiver and the benefit-risk statement and the 
justification by the Investigator will be maintained as source documents and will be reviewed 
by the DMC.

An Evaluation Period of up to approximately 5 years, which will start with V2, the EV, 
which is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of 
EP0069. Eligible subjects will enter EP0073 before the planned dose tapering in EP0069.
Subjects will be issued and return seizure diaries during each visit. Subjects must be educated 
to record all types of seizures that occur, any illness or injury, and all study medication intake
in their seizure diary and be educated to complete their diary entries after each seizure or at 
least once a day. Throughout the study, the Investigator also will be requested to periodically 
re-assess and re-confirm that the benefit-risk ratio for the subject on long-term treatment with 
the IMP, considering the knowledge of the IMP’s efficacy and safety profile and alternative 
treatment options, justifies continuation in the study. Narratives of benefit by the 
subject/caregiver and the benefit-risk statement and the justification by the Investigator will 
be captured in a dedicated form at the scheduled time points presented in Table 5‒2.
First year:
In the first month of EP0073, subjects will have 2 TCs (M1-Wk1 [TC1] and M1-Wk3 [TC2]) 
and 1 clinic visit (M1-Wk2 [V3]). During the 2 TCs, the site personnel will review changes 
in concomitant medications (including AEDs), confirm whether the subject experienced any 
AEs/SAEs, and ensure that subjects are compliant with their study medication dosing 
schedule as outlined in the protocol. 
During the second, third and fourth months, subjects will visit the clinic at M2 (V4, MEV),
M3 (V5, FEV), and M4 (V6, MEV).
Subjects will return to the clinic every 3 months for the remainder of the first year with FEV 
alternating with MEV: M7 (V7, FEV) and M10 (V8, MEV).
Second and third year:
For the second and third years, subjects will have clinic visits every 3 months, with MEVs 
alternating with FEVs/YEVs, beginning with M13 (V9, YEV).
Fourth and fifth year:
For subjects who continue to participate in EP0073 beyond the 3-year period, the subjects 
will have a clinic visit every 6 months with YEVs alternating FEVs.

A Taper Period starting at the LEPV of the Evaluation Period; during the Taper Period, 
subjects will start to gradually decrease their dose of UCB0942. The Taper Period is planned 
to be 3 weeks; however, a faster taper schedule than the suggested 3 weeks may be 
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implemented if medically necessary. A slower taper schedule of up to 6 weeks may be 
implemented as per the Investigator’s medical judgment. 

A SFU Period; subjects must return to the clinic 1 week after administration of the final dose 
of UCB0942 (SFU1). A FV will be scheduled 30 days after administration of the final dose 
of UCB0942 (SFU2).
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP0069. They will continue this dose in the current study and there will be no 
tapering from the EP0069 dose before they receive the first dose in EP0073; however, 
throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg (400mg bid); 
intermediate doses will not be allowed except for tapering and titration. Exceptions may be 
allowed after consultation with the PRA Medical Monitor. The dose of UCB0942 must always 
be administered as bid morning and evening doses, approximately 12 hours apart. The first dose 
of the current study will be the dose on the evening of V2.
Concomitant AEDs and AED dose(s), or VNS settings may be adjusted throughout EP0073 as 
per the Investigator’s clinical judgment based on tolerability and seizure control for each 
individual subject.
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. New concomitant AEDs may be introduced to optimize 
tolerability and seizure reduction. For details, please refer to Section 7.2.
If at any time, the subject and/or the Investigator decide to discontinue UCB0942, the subject 
should return for an EDV and gradually decrease their dose of UCB0942.
At the end of the Evaluation Period, subjects will return for a LEPV and will start to gradually 
decrease their dose of UCB0942. Subjects must return to the clinic for a visit at the end of the 
Taper Period. A suggested 3-week taper schedule and further details on dose tapering are given 
in Section 7.2.
The CIWA-B will be used to monitor for withdrawal signs/symptoms during the Taper and 
Safety Follow-Up Periods.
5.1.1
Study duration per subject
For each subject, the study will last from study entry for approximately 5 years or until either a 
marketing authorization is granted by any health authority for the adjunctive treatment for POS 
in adult subjects with highly drug-resistant focal epilepsy, or until UCB decides to close the 
study.
The end of the study is defined as the date of the last visit of the last subject in the study.
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5.1.2
Planned number of subjects and sites
It is estimated that approximately 40 subjects who completed EP0069 will be included in 
multiple sites in Europe.
5.1.3
Anticipated regions and countries
The study is planned to be performed in The Netherlands, Belgium, Bulgaria, and Germany. 
Other countries in the European Union can be added if deemed necessary by the Sponsor.
5.2
Visit schedule
The visit schedule is presented in Table 5‒1.
Visit windows will be as follows: ±3 days for the 1-month visit intervals, ±4 days for the 
3-month visit intervals, ±1 week for the 5- or 6-month visit intervals, and +7 days for SFU2.
Table 5‒1:
Study visit schedule
Month
Visit
Type of visit
First study year
M0
V1 (V13 of EP0069)
Screening Visit
M1
V2 (V15 of EP0069)
EV
M1-Wk1
TC1
TC
M1-Wk2
V3
MEV
M1-Wk3
TC2
TC
M1-Wk4
-a
-
M2
V4
MEV
M3
V5
FEV
M4
V6
MEV
M5
-
-
M6
-
-
M7
V7
FEV
M8
-
-
M9
-
-
M10
V8
MEV
M11
-
-
M12
-
-
Second study year
M13
V9
YEV
M16
V10
MEV
M19
V11
FEV
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Table 5‒1:
Study visit schedule
Month
Visit
Type of visit
M22
V12
MEV
Third study year
M25
V13
YEV
M28
V14
MEV
M31
V15
FEV
M34
V16
MEV
Fourth study year
M37
V17
YEV
M43
V18
FEV
Fifth study year
M49
V19
YEV
M55
V20
FEV
M58
V21
YEV and LEPV/EDV
Taper and SFU Periodsb
Taper Period
V22
End of Taper Visit
SFU1
V23
SFU at 1 week after final dose
SFU2
V24
SFU at 30 days after final dose (FV)
EDV=Early Discontinuation Visit; EV=Entry Visit; FEV=Full Evaluation Visit; FV=Final Visit; LEPV=Last 
Evaluation Period Visit; M=Month; MEV=Minimal Evaluation Visit; SFU=Safety Follow-Up; TC=Telephone Call; 
V=Visit; Wk=Week; YEV=Yearly Evaluation Visit
a The "-" denotes that no visit is scheduled in that month
b Taper and SFU Periods to start with EDV or LEPV.
Please note that unscheduled visits or telephone contacts may be performed at any time after V1 
at the discretion of the Investigator. 
An unscheduled visit may be performed, for example, when the UCB0942 dose is increased or 
decreased. The following assessments will be required during this visit:

Recording of AEs

Recording of concomitant medications 

Contact interactive response technology (IRT; in case of increase or decrease in UCB0942 
dose)
In addition to the required assessments listed above, further assessments can be completed at the 
unscheduled visit as needed and may include 12-lead ECG, vital signs, Columbia-Suicide 
Severity Rating Scale (C-SSRS), BPRS, laboratory tests (including urine pregnancy test [for 
women of childbearing potential]), etc. Study medication may be dispensed, if required.
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An unscheduled visit or a telephone contact is recommended to follow up with the evolution of 
subject’s condition subsequent to the increase or decrease of the UCB0942 dose.
Reasons for any unscheduled visits or telephone contacts should be documented.
5.3
Schedule of study assessments
The schedule of study assessments is presented in Table 5‒2.
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Table 5‒2:
Schedule of study assessments
Assessments
Screening Period
Evaluation Period
Taper Perioda
SFU Period
Screening 
Visit
EV
Telephone 
Calls
FEV
MEV
YEV and 
LEPV 
(V21)/EDV
End of Taper 
Visit
SFU1 at 1 
week
SFU2 at 
30 days/
FV
Visit
V1 (V13 of 
EP0069)
V2 (V15 of 
EP0069)
TC1, TC2
V5, V7, V11, 
V15, V18, 
V20
V3, V4, V6, 
V8, V10, 
V12, V14, 
V16
V9, V13, 
V17, V19, 
V21
V22
V23
V24
Week/Month
M0
M1
M1-Wk1, 
M1-Wk3
M3, M7, 
M19, M31, 
M43, M55
M1-Wk2,
M2, M4, 
M10, M16, 
M22, M28, 
M34
M13, M25, 
M37, M49, 
M58
NA
NA
NA
Written informed consent
X
Demographic datab
X
Verification of 
inclusion/exclusion 
criteriac
X
X
Withdrawal criteria
X
X
X
X
General medical/ 
procedure historyb
X
Complete physical 
examination
X
X
X
X
Brief physical 
examination
X
X
X
Complete neurological 
examination
X
X
X
X
X
X
Brief neurological 
examination
X
BMI
X
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Table 5‒2:
Schedule of study assessments
Assessments
Screening Period
Evaluation Period
Taper Perioda
SFU Period
Screening 
Visit
EV
Telephone 
Calls
FEV
MEV
YEV and 
LEPV 
(V21)/EDV
End of Taper 
Visit
SFU1 at 1 
week
SFU2 at 
30 days/
FV
Visit
V1 (V13 of 
EP0069)
V2 (V15 of 
EP0069)
TC1, TC2
V5, V7, V11, 
V15, V18, 
V20
V3, V4, V6, 
V8, V10, 
V12, V14, 
V16
V9, V13, 
V17, V19, 
V21
V22
V23
V24
Week/Month
M0
M1
M1-Wk1, 
M1-Wk3
M3, M7, 
M19, M31, 
M43, M55
M1-Wk2,
M2, M4, 
M10, M16, 
M22, M28, 
M34
M13, M25, 
M37, M49, 
M58
NA
NA
NA
Vital signs (BP, pulse, 
and RR) and body weight
X
X
X
X
X
X
X
Echocardiogram
X
X
Xd
X
X
12-lead ECGe
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
Concomitant AEDs
X
X
X
X
X
X
X
X
Screening for drug and 
alcohol usef
X
X
X
Laboratory tests
Chemistry/hematology
X
X
X
X
Urinalysis
X
X
X
X
Serum pregnancy testg
X
X
Urine pregnancy testg
X
X
X
X
X
C-SSRS (since last visit)
X
X
X
X
X
X
X
QOLIE-31-Ph
X
X
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Table 5‒2:
Schedule of study assessments
Assessments
Screening Period
Evaluation Period
Taper Perioda
SFU Period
Screening 
Visit
EV
Telephone 
Calls
FEV
MEV
YEV and 
LEPV 
(V21)/EDV
End of Taper 
Visit
SFU1 at 1 
week
SFU2 at 
30 days/
FV
Visit
V1 (V13 of 
EP0069)
V2 (V15 of 
EP0069)
TC1, TC2
V5, V7, V11, 
V15, V18, 
V20
V3, V4, V6, 
V8, V10, 
V12, V14, 
V16
V9, V13, 
V17, V19, 
V21
V22
V23
V24
Week/Month
M0
M1
M1-Wk1, 
M1-Wk3
M3, M7, 
M19, M31, 
M43, M55
M1-Wk2,
M2, M4, 
M10, M16, 
M22, M28, 
M34
M13, M25, 
M37, M49, 
M58
NA
NA
NA
Narratives of benefit and 
benefit-risk assessmenti
X
X
X
X
X
BPRS
X
X
X
X
X
MMSE
X
X
X
X
X
CIWA-B
Xj
X
X
X
Sample for UCB0942, 
, and 
 plasma 
concentrationsk
X
X
X
Call IRT
X
X
X
X
X
Dispense subject diary
X
X
X
X
X
X
Subject diary return
X
X
X
X
X
X
Dispense study 
medication
X
X
X
X
Study medication return
X
X
X
X
Adverse event reporting
X
X
X
X
X
X
X
X
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Table 5‒2:
Schedule of study assessments
Assessments
Screening Period
Evaluation Period
Taper Perioda
SFU Period
Screening 
Visit
EV
Telephone 
Calls
FEV
MEV
YEV and 
LEPV 
(V21)/EDV
End of Taper 
Visit
SFU1 at 1 
week
SFU2 at 
30 days/
FV
Visit
V1 (V13 of 
EP0069)
V2 (V15 of 
EP0069)
TC1, TC2
V5, V7, V11, 
V15, V18, 
V20
V3, V4, V6, 
V8, V10, 
V12, V14, 
V16
V9, V13, 
V17, V19, 
V21
V22
V23
V24
Week/Month
M0
M1
M1-Wk1, 
M1-Wk3
M3, M7, 
M19, M31, 
M43, M55
M1-Wk2,
M2, M4, 
M10, M16, 
M22, M28, 
M34
M13, M25, 
M37, M49, 
M58
NA
NA
NA
AED=antiepileptic drug; BMI=body mass index; BP=blood pressure; BPRS=Brief Psychiatric Rating Scale; CIWA-B=Clinical Institute Withdrawal Assessment-
Benzodiazepines; C-SSRS=Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; EDV=Early Discontinuation Visit; EV=Entry Visit; FEV=Full Evaluation 
Visit; FV=Final Visit; IRT=interactive response technology; LEPV=Last Evaluation Period Visit; M=Month; MEV=Minimal Evaluation Visit; MMSE=Mini-Mental 
State Examination; QOLIE-31-P=Quality of Life Inventory in Epilepsy-31-P; RR=respiratory rate; SFU=Safety Follow-Up; TC=Telephone Call; V=Visit; Wk=Week; 
YEV=Yearly Evaluation Visit
a During the Taper Period, dose tapering will be done through TCs; a clinical visit will be performed at end of Taper Period, ie, V22. The Taper Period is 
planned to be 3 weeks; however, a faster taper schedule than the suggested 3 weeks may be implemented if medically necessary. A slower taper schedule 
of up to 6 weeks may be implemented as per the Investigator’s medical judgment.
b Demographic and general medical/procedure history data will be obtained from EP0069 and updated if necessary. Information regarding surgical 
evaluation, working status, caregiver support, and supervision should be collected within 30 days after Protocol Amendment 2 is approved.
c From EP0073 study.
d No echocardiogram will be done at V3, V14, and V16.
e Standard 12-lead ECGs will be recorded prior to laboratory tests.
f The drug screen will include amphetamines, benzodiazepines, barbiturates, cocaine, cannabinoids, methadone, opiates, and alcohol. Use of AED from one 
of the classes mentioned will be allowed if allowed by inclusion and exclusion criteria.
g For females of childbearing potential only.
h The QOLIE-31-P will be completed by all subjects who are not mentally impaired, prior to any other study procedures at the visit.
i Narratives of benefit and benefit-risk assessment can be completed any time during the Screening Period after obtaining informed consent and before 
eligibility check at V2.
j During the Evaluation Period, the CIWA-B will be performed at V21 only (LEPV) or at EDV.
k Obtain blood samples for measurement of plasma concentration of UCB0942 and metabolites at V3, V4, V5, V6, V7, V8 and V9.
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5.4
Rationale for study design and selection of dose
This OLE study will assess the long-term safety and efficacy of UCB0942 in the adjunctive 
treatment of seizures with or without secondary generalization in adult subjects with highly 
drug-resistant focal epilepsy. Also, the the effects of UCB0942 on the subject’s quality of life 
will be explored.
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP0069. In EP0073 doses can range from 50mg bid to 400mg bid. The highest 
UCB0942 dose of 400mg bid used in this study has been chosen because it is the maximum 
tolerated dose in Phase 1 studies. This dose is expected to:
1. Achieve exposures similar to those that show unprecedented efficacy in the rat amygdala 
kindling model of drug-resistant focal epilepsy,
2. Achieve full and constant SV2 occupancy based on modeling predictions, and
3. Achieve 10 to 15% occupancy of the cBZR site on the GABA-A receptor.
Throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg (400mg bid); 
intermediate doses will not be allowed except for tapering and titration unless agreed by the PRA 
Medical Monitor.
6
SELECTION AND WITHDRAWAL OF SUBJECTS
6.1
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. A written Informed Consent form approved by the IEC is signed and dated by the subject, 
after the Investigator assesses whether the subject is able to understand the potential risks and 
benefits of participating in the study.
2. Subject and/or caregiver 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 must have completed V13 of the Outpatient Maintenance Period of EP0069 to be 
eligible for enrollment into EP0073.
4. In EP0069, the subject demonstrated a reduction in frequency and/or severity of seizures as 
compared to baseline that is considered clinically significant by the Investigator and 
significant by the subject.
5. In EP0069, the subject experiences substantial benefit from UCB0942 with acceptable 
tolerability according to the subject and Investigator.
6. No tolerability issues that can outweigh attained benefits, in the opinion of the Investigator.
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7. Female subjects of nonchildbearing potential (premenarcheal, postmenopausal for at least 
2 years, bilateral oophorectomy or tubal ligation, and complete hysterectomy) are eligible. 
Female subjects of childbearing potential are eligible if they use medically accepted 
contraceptive methods. Oral or depot contraceptive treatment used with an additional barrier 
contraception method, monogamous relationship with vasectomized or female partner, or 
double-barrier contraception are acceptable methods. The subject must understand the 
consequences and potential risks of inadequately protected sexual activity, be educated about 
and understand the proper use of contraceptive methods, and undertake to inform the 
Investigator of any potential change in status. Abstinence will be considered as an acceptable 
method of contraception if the Investigator can document that the subject agrees to be 
compliant when it is in line with the preferred and usual lifestyle of the subject.
8. Male subject confirms that, during the study period and for a period of 3 months after the 
final dose, when having sexual intercourse with a woman of childbearing potential, he will 
use a barrier contraceptive (eg, condom).
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Subject has any severe medical, neurological, or psychiatric condition, or laboratory value
which may have an impact on the safety of the subject.
2. 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 C-SSRS. The subject 
should be referred immediately to a Mental Healthcare Professional and must be withdrawn 
from the study.
3. Subject has developed a known hypersensitivity to any components of the IMP as stated in 
this protocol during participation in EP0069.
4. Subject has poor compliance with the visit schedule of medication intake in the EP0069 
study according to the Investigator’s judgment.
5. Subject plans participation in any other clinical study of another investigational drug or 
device while participating in this study (with the exception of participating in the EP0069 
study).
6. Subject is a woman who is pregnant or lactating.
7. Subject has taken other (non-AED) prescription, non-prescription, dietary (eg, grapefruit or 
passion fruit), or herbal products that are potent inducers or inhibitors of the CYP3A4 
pathway for 2 weeks (or 5 half-lives whichever is longer) prior to study entry.
8. Subject has an abnormality in the 12-lead 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:

Prolonged QTc (Bazett’s, machine-read) interval defined as >450ms for males and 
>470ms for females

Bundle branch blocks and other conduction abnormalities other than mild first degree 
atrioventricular block (defined as PR interval ≥220ms)
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
Irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular or rare 
ventricular ectopic beats

In the judgment of the Investigator, T-wave configurations are not of sufficient quality 
for assessing QT interval duration
9. Subject has a history of unexplained syncope or a family history of sudden death due to long
QT syndrome.
10. Subject has a clinically significant abnormality on echocardiography at the EV (V2) of 
EP0073.
11. Subject has any medical condition which, in the Investigator’s opinion, warrants exclusion.
12. 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 (≥1.5xULN total bilirubin if known Gilbert’s syndrome) at the EV (V2) 
of EP0073 (V15 of EP0069). 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 enrolled 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 in the electronic Case Report form (eCRF).
If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at screening
(ie, the value is >ULN but ≤2xULN at the EV [V2] of EP0073), 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.
6.3
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care.
Investigators should attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow up, the Investigator should make an 
effort (at least 1 phone call and 1 written message to the subject), and document his/her effort 
(date and summary of the phone call and copy of the written message in the source documents), 
to complete the final evaluation. All results of these evaluations and observations, together with a 
narrative description of the reason(s) for removing the subject, must be recorded in the source 
documents. The eCRF must document the primary reason for withdrawal or discontinuation.
Investigators should contact the PRA Medical Monitor, whenever possible, to discuss the 
withdrawal of a subject in advance.
Subjects must be withdrawn from the study if any of the following events occur:
1. Withdrawal for safety reasons by the Investigator and/or when the benefit-risk ratio of the 
IMP treatment is 0 to 4 (on a scale from 0 to 10), indicating the risks outweigh the benefits.
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2. Subject is suspected of having a serious multiorgan hypersensitivity reaction. Serious 
suspected multiorgan hypersensitivity cases may be identified and reported to the Sponsor by 
the Investigator using the following algorithm: 

An AE or laboratory value (as defined below) suggestive of internal organ involvement 
(including but not limited to hepatitis, nephritis, pneumonitis, carditis, colitis, 
encephalitis, pancreatitis, myositis, arthritis, or hematologic system involvement) 
combined with at least one of the following: fever, rash, lymphadenopathy, or 
eosinophilia. 

Treatment-emergent abnormal laboratory value criteria suggestive of internal organ 
involvement or eosinophilia:

Eosinophils percentage ≥10%

Eosinophils absolute ≥0.5G/L

Neutrophils absolute <1.5G/L

Platelets absolute ≤100G/L
3. Subject cannot tolerate the minimum UCB0942 dose of 50mg bid (100mg/day).
4. Subject and/or Investigator does not think that the investigational drug is effective (ie, lack or 
loss of efficacy).
5. Subject is lost to follow up.
6. Subject is noncompliant with the study procedures or medications in the opinion of the 
Investigator.
7. Subject takes prohibited concomitant medications: 

Carbamazepine, phenytoin, phenobarbital, primidone, or other AEDs that are strong 
CYP3A4 inducers

Benzodiazepines taken >3 times per week

Zolpidem, zaleplon, or zopiclone taken >3 times per week

Tiagabine

Felbamate

Vigabatrin

Strong non-AED CYP3A4 inducers/inhibitors (ie, prescription drugs, nonprescription 
drugs, dietary [eg, grapefruit or passion fruit], or herbal products)
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugI
nteractionsLabeling/ucm093664.htm)
8. Subject withdraws his/her consent.
9. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test.
10. The Sponsor or a regulatory agency requests withdrawal of the subject.
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11. Subject has active suicidal ideation without a specific plan as indicated by a positive response 
(“Yes”) to Question 4 of the “Since Last Visit” version of the C-SSRS. The subject should be 
referred immediately to a Mental Healthcare Professional and may be withdrawn from the 
study based upon the Investigator’s judgment of benefit/risk of continuing the subject in the 
study/on study medication. Subject has 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 C-SSRS. The subject should be referred immediately to a Mental Healthcare Professional 
and must be withdrawn from the study.
12. A prolongation or worsening of overall seizure duration, frequency, type, or pattern 
considered by the Investigator as serious enough to warrant discontinuation from the study.
13. An ECG shows an absolute value for QT corrected for heart rate using Bazett’s formula
(QTcB) or QT corrected for heart rate using Fridericia’s formula (QTcF) ≥500ms or ≥60ms 
above baseline.
14. Subject develops second- or third-degree atrioventricular block or another clinically relevant 
change in ECG as determined by the Investigator.
15. Subject has an abnormality on the echocardiogram that is clinically concerning or that 
worsens over time.
16. For subjects developing psychiatric/mood/behavioral signs or disturbances (see examples in 
list below) that are clinically concerning or that worsen over time, the study drug dose should 
be gradually reduced and, if symptoms persist, withdrawal from study should be 
recommended. Subjects should be referred to a mental health professional, and continuation 
of the study treatment should only be allowed with the approval and under close oversight of 
the mental health specialist, and upon confirmation of the positive benefit-risk by the 
Investigator.
a.
Auditory or visual hallucinations
b. Delusions / paranoia / grandeur
c.
Disorganized thought process
d. Agitation / aggression / apathy
e.
Dysphoria / depression / mood lability / euphoria
f.
Disinhibition
g. Cognitive changes / memory impairment / delirium
h. Aberrant motor behavior
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria
Subjects with potential drug-induced liver injury (PDILI) must be assessed to determine if IMP 
must be discontinued. In addition, all concomitant medications and herbal supplements that are 
not medically necessary should also be discontinued. 
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The PDILI criteria below require immediate and permanent discontinuation of IMP: 

Subjects with either of the following:

ALT or AST ≥5xULN

ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN 
The PDILI criterion below requires immediate discontinuation of IMP:

Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%).
If a nondrug-related cause for the symptoms can be confirmed, these subjects may resume IMP 
administration after discussion with the responsible UCB physician, but only when the 
requirements for rechallenge with IMP as provided in Section 11.6.1.2.1 are followed.
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
Investigator. 

Subjects with ALT or AST ≥3xULN (and ≥2x baseline) and <5xULN, total bilirubin 
<2xULN, and no eosinophilia (ie, ≤5%), with no fever, rash, or symptoms of hepatitis (eg, 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness).
Evaluation of PDILI must be initiated as described in Section 11.6.1. If subjects are unable to 
comply with the applicable monitoring schedule, IMP must be discontinued immediately.
Investigators should attempt to obtain information on subjects in the case of IMP discontinuation 
to complete the final evaluation. Subjects with PDILI should not be withdrawn from the study 
until investigation and monitoring are complete. All results of these evaluations and 
observations, as well as the reason(s) for IMP discontinuation and subject withdrawal (if 
applicable), must be recorded in the source documents. The eCRF must document the primary 
reason for IMP discontinuation.
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7
STUDY TREATMENT(S)
7.1
Description of investigational medicinal product(s)
The IMP is supplied as white, film-coated tablets in strengths of 25mg, 100mg, and 200mg. 
7.2
Treatments to be administered
Subjects being enrolled in the current study from EP0069 will continue their dose in the current 
study and there will be no tapering from the EP0069 dose before they receive the first dose in 
EP0073; however, throughout the Evaluation Period, the Investigator will be allowed to increase 
or decrease the dose of UCB0942 to optimize tolerability and seizure control for each subject. 
Increases or decreases to the dose of UCB0942 should be made in steps not exceeding 
200mg/day per week; an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is 
allowed. A faster decrease of the dose than 200mg/day per week is allowed when it is clinically 
appropriate in the Investigator's medical judgment. Daily UCB0942 doses during this study may 
be 100mg (50mg bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration unless 
agreed by the PRA Medical Monitor. The dose of UCB0942 must always be administered as bid 
morning and evening doses, approximately 12 hours apart. The first dose of the current study 
will be the dose on the evening of V2. 
Concomitant AEDs and AED dose(s), or VNS settings may be adjusted throughout EP0073 as 
per the Investigator’s clinical judgment based on tolerability and seizure control for each 
individual subject.
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. The PRA Medical Monitor must be consulted prior to 
initiation of concomitant AED withdrawal. New concomitant AEDs may be introduced to 
optimize tolerability and seizure reduction, if the concomitant medication has been approved for 
focal seizures by the health authority of the subject’s country of residence, taking the 
drug-to-drug interactions profile of UCB0942 into account. New AEDs (with the exception of 
AEDs listed in the prohibited medication section, Section 7.8.2) should be added only when the 
subject has not optimally or adequately responded to a maximum tolerated dose of UCB0942.
If at any time, the subject and/or the Investigator decide to discontinue UCB0942, the subject 
should return for an EDV and gradually decrease their dose of UCB0942 as described below.
At the end of the Evaluation Period, subjects will return for a LEPV and will start to gradually 
decrease their dose of UCB0942. During the Taper Period, sites should contact subjects by 
telephone to discuss their dose adjustments. Subjects must return to the clinic for a visit at the 
end of the Taper Period. A suggested 3-week taper schedule is described in Table 7‒1. 
Table 7‒1:
Three-week taper schedule for UCB0942
Daily dose at 
LEPV/EDV (mg/day)
Taper Week 1 
(mg/day)
Taper Week 2 
(mg/day)
Taper Week 3 
(mg/day)
600 and 800
500a
300a
100
400
300a
100
-
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Table 7‒1:
Three-week taper schedule for UCB0942
Daily dose at 
LEPV/EDV (mg/day)
Taper Week 1 
(mg/day)
Taper Week 2 
(mg/day)
Taper Week 3 
(mg/day)
200
100
-
-
100
-
-
-
EDV=Early Discontinuation Visit; LEPV=Last Evaluation Period Visit
a It is recommended to divide uneven doses with a lower dose in the morning and a higher dose in the evening to the 
discretion of the Investigator.
A faster taper schedule than the suggested 3 weeks should only be implemented if medically 
necessary. A slower taper schedule of up to 6 weeks may be implemented as per the 
Investigator’s medical judgment. During the Taper Period, the dose of UCB0942 must always be 
administered as bid morning and evening doses, approximately 12 hours apart.
During the Taper Period, the Investigator is allowed to add any additional AED(s) following the 
Investigator's medical judgment (with the exception of AEDs listed in the prohibited medication 
section, Section 7.8.2). 
The CIWA-B will be used to monitor for withdrawal signs/symptoms during the Taper and 
Safety Follow-Up Periods.
7.3
Packaging
UCB0942 tablets are manufactured, packaged and labeled according to Good Manufacturing
Practice (GMP) guidelines and applicable laws or regulations. The IMP is suitably packaged in 
such a way to protect the IMP from deterioration during transport and storage. Packaging details 
are included in the IMP Handling Manual.
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Conference on 
Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and GMP and will include any 
locally required statements. If necessary, labels will be translated into the local language.
7.5
Handling and storage requirements
The Investigator (or designee) is responsible for the safe and proper storage of UCB0942 at the 
site. Investigational medicinal product stored by the Investigator is to be kept in a secured area 
with limited access according to the storage conditions mentioned on the label.
Appropriate storage conditions must be ensured either by controlling the temperature (eg, room, 
refrigeration unit) or by completion of a temperature log in accordance with local requirements 
on a regular basis (ie, every working day), showing actual and minimum/maximum temperatures 
reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
and IMP information contained in the IMP Handling Manual. The Investigator (or designee) will 
instruct the subject to store the IMP following the instructions on the label.
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7.6
Drug accountability
A Drug Accountability form will be used to record UCB0942 dispensing and return information 
on a by-subject basis and will serve as source documentation during the course of the study. 
Details of any UCB0942 lost (due to breakage or wastage), not used, disposed of at the study 
site, or returned to the Sponsor or designee must also be recorded on the appropriate forms. All
supplies and pharmacy documentation must be made available throughout the study for UCB (or 
designee) to review.
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of UCB0942 until returned or destroyed at the site per local procedures.
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee.
The Investigator must ensure that UCB0942 is used only in accordance with the protocol.
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers), partially used and unused UCB0942 containers must be reconciled and either be 
destroyed at the site per local procedures or returned to UCB (or designee), preferably in their 
original package. Investigational medicinal product intended for the study cannot be used for any 
other purpose than that described in this protocol.
7.7
Procedures for monitoring subject compliance
At each visit after UCB0942 is dispensed, subjects must return all unused UCB0942 and empty 
UCB0942 containers. Drug accountability must be done in the subject’s presence in order to 
obtain explanations regarding discrepancies in compliance with the dosing regimen. Drug 
accountability must be recorded on the Drug Accountability form.
If a subject is found to be persistently noncompliant (defined as less than 75% or more than 
125% compliant with the dosage schedule), the Sponsor, in conjunction with the Investigator, 
will make a decision as to whether the subject should be withdrawn from the study.
Timely completion of the subject diary is essential for evaluation of safety, efficacy, and study 
medication intake. A caregiver is allowed to help the subject with the completion of the subject 
diary. Subject diary completion will be evaluated at each visit.
7.8
Concomitant medication(s)/treatment(s)
7.8.1
Permitted concomitant treatments (medications and therapies)
The following concomitant medications are permitted during the study:

All subjects will enter EP0073 using their current AED regimen. Concomitant AEDs and 
AED dose(s), or VNS settings may be adjusted throughout EP0073 as per the Investigator’s 
clinical judgment based on tolerability and seizure control for each individual subject. 
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. New concomitant AEDs may be introduced to 
optimize tolerability and seizure reduction. Changes in AEDs should be discussed with the 
PRA Medical Monitor on an individual and case-by-case basis.

Oxcarbazepine, eslicarbazepine.
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
Benzodiazepines (as a rescue medication ≤3 doses within 7 days).

Other medication, not mentioned as prohibited.
7.8.2
Prohibited concomitant treatments (medications and therapies)
The following concomitant medications are prohibited during the study (this is not a complete 
list of prohibited medications):

Carbamazepine, phenytoin, phenobarbital, primidone, or other AEDs that are strong 
CYP3A4 inducers

Benzodiazepines taken >3 times per week (ie, >3 doses within 7 days)

Zolpidem, zaleplon, or zopiclone taken >3 times per week

Tiagabine

Felbamate

Vigabatrin

Strong non-AED CYP3A4 inducers/inhibitors (ie, prescription drugs, nonprescription drugs, 
dietary [eg, grapefruit or passion fruit], or herbal products)
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInter
actionsLabeling/ucm093664.htm)
The following medications* should not be administered concomitantly with UCB0942. 
However, if subjects are already taking these medications prior to Amendment 3, they may 
continue to do so, but close monitoring should be implemented.

Strong CYP2C19 inhibitors (eg, fluconazole, fluoxetine, fluvoxamine, and ticlopidine)

Strong CYP2C19 inducers (eg, including rifampicin and ritonavir)

CYP2C19 sensitive substrates (eg, s-mephenytoin and omeprazole)
*For more details refer to Table 3-1, Table 3-2, and Table 3-3 in FDA Drug Development 
Resources, Drug development and drug interactions: Table of substrates, inhibitor and inducers.
7.8.3
Rescue medication
Benzodiazepines can be used as rescue medication (≤3 doses within 7 days).
7.9
Blinding
This is an OLE study so no blinding is required. A DMC (see Section 13.8) will review blinded 
data up until final unblinding from EP0069 and data from the OLE EP0073 studies to provide an 
ongoing evaluation of the safety signals and the benefit-risk balance for the study subjects.
7.10
Randomization and numbering of subjects
Randomization is not applicable in the current study. Subjects will be identified with the subject 
number they received in the EP0069 study.
An IRT will generate individual assignments for subject kits of UCB0942, as appropriate, 
according to the visit schedule and the dose the subject should receive.
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The subject number will be required in all communication between the Investigator or designee 
and the IRT regarding a particular subject. 
8
STUDY PROCEDURES BY VISIT 
Details of the study assessments to be performed at specific time points prior to and after 
UCB0942 administration are provided in Table 5‒2, and an outline of all assessments performed 
is provided in the sections below.
Visit windows will be as follows: ±3 days for the 1-month visit intervals, ±4 days for the 
3-month visit intervals, ±1 week for the 5- or 6-month visit intervals, and +7 days for SFU2.
8.1
Screening Period
The Screening Visit, V1, is the same as V13 (Day OP43) of the 8-week Outpatient Maintenance 
Period of EP0069. At the Screening Visit the following items will be covered:

Written informed consent

Review of inclusion/exclusion criteria (from EP0073)

Narratives of benefit and benefit-risk assessment
8.2
Evaluation Period
8.2.1
Entry Visit
The EV, V2, is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of 
EP0069. Data collected at V15 in EP0069 must also be recorded at V2 in the EP0073 eCRF.
During the EV the following assessments will be performed:

Review demographic, medical, medication, and procedural data from EP0069 and update 
where necessary; collect information regarding surgical evaluation, working status, caregiver 
support, and supervision within 30 days after Protocol Amendment 2 is approved.

Concomitant AEDs and non-AEDs; any ongoing concomitant medications from EP0069 
must also be recorded on the EP0073 eCRF. Details are provided in the eCRF Completion 
Guidelines.

Review of inclusion/exclusion criteria (from EP0073)

Calculation of body mass index (BMI)

Complete physical examination

Complete neurological examination

Vital signs (BP, pulse, and RR) and body weight

Echocardiogram (this can be done on another day within 1 week from the EV)

12-lead ECG (prior to laboratory tests)

Drug and alcohol screening

Clinical laboratory (clinical chemistry, hematology, and urinalysis)

Serum pregnancy test (female subjects of childbearing potential only)
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
C-SSRS (since last visit)

Narratives of benefit and benefit-risk assessment (if not performed at V1)

BPRS

MMSE

Call IRT

Dispense subject diary

Dispense study medication

AE reporting
8.2.2
Telephone Calls
The subject will be contacted by telephone in Week 1 (TC1) and Week 3 (TC2). During the 
Telephone Call the following items will be covered:

Withdrawal criteria

Concomitant medication recording

Concomitant AEDs

AE reporting
8.2.3
Minimal Evaluation Visit
The MEVs are planned in M1-Wk2 (V3), M2 (V4), M4 (V6), M10 (V8), M16 (V10), M22
(V12), M28 (V14) and M34 (V16). During the MEVs the following assessments will be 
performed:

Withdrawal criteria

Brief physical examination

Brief neurological examination

Vital signs (BP, pulse, and RR) and weight

Echocardiogram (not at V3, V14, and V16)

Concomitant medication recording

Concomitant AEDs

Urine pregnancy test (female subjects of childbearing potential only)

C-SSRS (since last visit)

Narratives of benefit and benefit-risk assessment

BPRS

MMSE

Blood sample for measurement of plasma concentration of UCB0942 and metabolites (only 
at V3, V4, V6, and V8)
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
Call IRT

Dispense and return subject diary

Dispense and return study medication

AE reporting
8.2.4
Full Evaluation Visit 
The FEVs are planned in M3 (V5), M7 (V7), M19 (V11), M31 (V15), M43 (V18), and M55
(V20). During the FEVs the following assessments will be performed:

Withdrawal criteria

Complete physical examination

Complete neurological examination

Vital signs (BP, pulse, and RR) and weight

Echocardiogram

12-lead ECG (prior to laboratory tests)

Concomitant medication recording

Concomitant AEDs

Drug and alcohol screening

Clinical laboratory (clinical chemistry, hematology, and urinalysis)

Urine pregnancy test (female subjects of childbearing potential only)

C-SSRS (since last visit)

QOLIE-31-P (will be completed by all subjects who are not mentally impaired, prior to any 
other study procedures at the visit)

Narratives of benefit and benefit-risk assessment

BPRS

MMSE

Blood sample for measurement of plasma concentration of UCB0942 and metabolites (only 
at V5 and V7)

Call IRT

Dispense and return subject diary

Dispense and return study medication

AE reporting
8.2.5
Yearly Evaluation Visit and Early Discontinuation Visit
The YEVs are planned in M13 (V9), M25 (V13), M37 (V17), M49 (V19), and M58 (V21; also 
LEPV).
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During the YEVs, and also during the EDV, the following assessments will be performed:

Withdrawal criteria

Complete physical examination

Complete neurological examination

Vital signs (BP, pulse, and RR) and weight

Echocardiogram

12-lead ECG (prior to laboratory tests)

Concomitant medication recording

Concomitant AEDs

Drug and alcohol screening

Clinical laboratory (clinical chemistry, hematology, urinalysis)

Urine pregnancy test (female subjects of childbearing potential only)

C-SSRS (since last visit)

QOLIE-31-P (will be completed by all subjects who are not mentally impaired, prior to any 
other study procedures at the visit)

Narratives of benefit and benefit-risk assessment

BPRS

MMSE

CIWA-B (at V21 only [LEPV] or at EDV)

Blood sample for measurement of plasma concentration of UCB0942 and metabolites (only 
at V9)

Call IRT

Dispense and return subject diary

Dispense and return study medication

AE reporting
For the EDV, if no visit can be scheduled, all efforts should be taken to contact the subject and 
obtain at least the following information:

Concomitant medication recording

AE reporting
8.3
Taper Period
An End of Taper Visit to the clinic is planned (V22) during which the following assessments will 
be performed:

Brief physical examination
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
Complete neurological examination

Vital signs (BP, pulse, and RR) and weight

Concomitant medication recording

Concomitant AEDs

Urine pregnancy test (female subjects of childbearing potential only)

C-SSRS (since last visit)

CIWA-B

Call IRT

Dispense and return subject diary

Return study medication

AE reporting
8.4
Safety Follow-Up Period
8.4.1
Safety Follow-Up Visit 1
Subjects must return to the clinic 1 week after administration of the final dose of study 
medication (SFU1). During SFU1, the following assessments will be performed:

Brief physical examination

Complete neurological examination

Vital signs (BP, pulse, and RR) and body weight

Concomitant medication recording

Concomitant AEDs

Urine pregnancy test (female subjects of childbearing potential only)

C-SSRS (since last visit)

CIWA-B

Dispense and return subject diary

AE reporting
8.4.2
Safety Follow-Up Visit 2
A FV will be scheduled 30 days after administration of the final dose of UCB0942 (SFU2). 
During SFU2, the following assessments will be performed:

Complete physical examination

Complete neurological examination

Vital signs (BP, pulse, and RR) and body weight

Echocardiogram
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
12-lead ECG (prior to laboratory tests)

Concomitant medication recording

Concomitant AEDs

Clinical laboratory (clinical chemistry, hematology, and urinalysis)

Serum pregnancy test (female subjects of childbearing potential only)

C-SSRS (since last visit)

Narratives of benefit and benefit-risk assessment

BPRS

MMSE

CIWA-B

Return subject diary

AE reporting
8.5
Unscheduled Visit/Telephone Contact
Please note that unscheduled visits or telephone contacts may be performed at any time after V1 
at the discretion of the Investigator. 
An unscheduled visit may be performed, for example, when the UCB0942 dose is increased or 
decreased. The following assessments will be required during this visit:

Recording of AEs

Recording of concomitant medications 

Contact IRT (in case of increase or decrease in UCB0942 dose)
In addition to the required assessments listed above, further assessments can be completed at the 
unscheduled visit as needed and may include 12-lead ECG, vital signs, C-SSRS, BPRS, 
narratives of benefit and benefit-risk assessment, laboratory tests (including urine pregnancy test 
[for women of childbearing potential]), etc. Study medication may be dispensed, if required.
An unscheduled visit or a telephone contact is recommended to follow up with the evolution of 
subject’s condition subsequent to the increase or decrease of the UCB0942 dose.
Reasons for any unscheduled visits or telephone contacts should be documented.
9
ASSESSMENT OF EFFICACY
The efficacy variables are described in detail in Section 4.2.
9.1
Seizure frequency
During the study, subjects will keep diaries to record daily seizure activity from the EV until the 
end of study participation. Subjects should be reminded to bring their diaries with them to each 
clinic visit. 
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The written information will be discussed with the subjects at each visit in order to ensure 
completeness and accuracy. As a result of the discussion, the Investigator will assess the seizures 
according to the International League Against Epilepsy codes and record the seizure types and 
frequency in the eCRF; he/she will also confirm the presence of AEs if applicable.
Subjects should record all types of seizures that occur in their diary and be educated to complete 
their diary entries after each seizure or at least once a day (eg, when taking evening tablets). A 
caregiver can assist in completing the diary if necessary. Substantial noncompliance with diary 
completion (seizure recording) may result in subject discontinuation from the study at any time 
by the Investigator or the Sponsor; see Section 6.3.
The following seizure information will be recorded in the diary:

Seizure type

Seizure frequency
9.2
Quality of Life Inventory in Epilepsy-31-P
The QOLIE-31-P assesses subject functioning and health-related quality of life.
The QOLIE-31-P is an adaptation of the original QOLIE 31 instrument (Cramer and Van 
Hammée, 1998) that includes 30 items grouped into 7 multi item subscales (Seizure Worry [5 
items], Overall Quality of Life [2 items], Emotional Well-being [5 items], Energy/Fatigue [4 
items], Cognitive Functioning [6 items], Medication Effects [3 items], and Daily 
Activities/Social Functioning [5 items]) and 1 health status item.
In addition to the 31 items of the QOLIE-31, the QOLIE-31-P contains 7 items assessing the 
degree of “distress” associated with the topic of each subscale (ie, distress items) and 1 item 
asking about the relative importance of each subscale topic (ie, prioritization item).
The QOLIE-31-P will be completed at the scheduled time points presented in Table 5‒2. At the 
very beginning of the visit, the QOLIE-31-P will be provided to all subjects. The subject will be 
asked to complete the questionnaire on his/her own. Once completed, the subject will return the 
completed questionnaire to the Investigator or designee, who will verify that all questions have 
been answered. Further details about the QOLIE-31-P will be covered in the Study Manual.
10
ASSESSMENT OF PHARMACOKINETICS
10.1
Sampling procedures
Blood samples for PK will be obtained at the scheduled time points presented in Table 5‒2.
Exact sampling times will be recorded in the eCRF. 
Detailed information on the collection, storage, preparation, and shipping of samples will be 
presented in a Laboratory Manual.
10.2
Bioanalytical methods
Plasma concentrations of UCB0942 and metabolites 
 and 
 
will be determined using validated bioanalytical methods.
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11
ASSESSMENT OF SAFETY
11.1
Adverse events
11.1.1
Definition of adverse event
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
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.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol, must be reported in the eCRF even if no IMP was taken but specific 
study procedures were conducted. This includes all AEs not present prior to the initial visit and 
all AEs that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
Investigator from the subject’s history or the Prospective Outpatient Baseline Period from the 
EP0069 study.
11.1.2
Procedures for reporting and recording adverse events
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
In addition, the Investigator should review any self-assessment procedures (eg, diary cards) 
employed in the study.
11.1.3
Description of adverse events
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF 
and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (eg, diary card) and the corresponding medical terminology should be 
clarified in the source documentation.
Details for completion of the Adverse Event eCRF (including judgment of relationship to IMP) 
are described in the eCRF Completion Guidelines.
11.1.4
Follow up of adverse events
An AE should be followed until it has resolved, has a stable sequelae, the Investigator
determines that it is no longer clinically significant, or the subject is lost to follow up. 
If an AE is ongoing at the end of the study for a subject, follow up should be provided until 
resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow up. If no follow up is provided, the 
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Investigator must provide a justification. The follow up will usually be continued for 30 days 
after the subject has discontinued his/her IMP.
In case of cardiac treatment-emergent AEs (TEAEs) associated with echocardiographic findings, 
the subject must be withdrawn from the study if the finding is clinically concerning or worsens 
over time, and the following should be completed:

The subject should return for an EDV

The subject should immediately stop the intake of UCB0942 or be down titrated as instructed 
at the EDV

Safety Follow-up Visits should be scheduled 1 week and 30 days after the subject has 
discontinued UCB0942
These TEAEs should be followed up at least 6 months or until they have resolved, have a stable 
sequelae, or the subject is lost to follow up.
11.1.5
Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:

The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening”

The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one
11.1.6
Pregnancy
If an Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the Investigator must immediately notify UCB’s Patient Safety (PS) department by providing the 
completed Pregnancy Report and Outcome form (for contact details see Serious Adverse Event 
reporting information at the beginning of this protocol). The subject should be withdrawn from 
the study as soon as pregnancy is known (by positive pregnancy test), and the following should 
be completed:

The subject should return for an early discontinuation visit.

The subject should immediately stop the intake of UCB0942 or be down titrated as instructed 
at the EDV.

Safety Follow-Up Visits should be scheduled 1 week and 30 days after the subject has 
discontinued UCB0942.
The Investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
The pregnancy will be documented on the Pregnancy Report and Outcome form provided to the 
Investigator. The progression of the pregnancy and the eventual birth (if applicable) must be 
followed up using the Pregnancy Report and Outcome form in which the Investigator has to 
report on the health of the mother and of the child. Every reasonable attempt should be made to 
follow the health of the child for 30 days after birth for any significant medical issues. In certain 
circumstances, UCB may request that follow up is continued for a period longer than 30 days. If 
the subject is lost to follow up and/or refuses to give information, written documentation of 
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attempts to contact the subject needs to be provided by the Investigator and filed at the site. 
UCB’s PS department is the primary contact for any questions related to the data collection for 
the pregnancy, eventual birth, and follow up.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
Investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent form that has been approved by the responsible IEC and should be 
available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/CRO contract monitor for the study. The Investigator will 
complete the Pregnancy Report and Outcome form and send it to UCB’s PS department (for 
contact details see Serious Adverse Event reporting information at the beginning of this protocol)
only after the partner has agreed that additional information can be captured and has provided the 
signed Partner Pregnancy Consent form. UCB’s PS department is also the primary contact for 
any questions related to the data collection for the partner pregnancy, eventual birth, and follow 
up.
A pregnancy becomes an SAE in the following circumstances: miscarriage, abortion (elective or 
spontaneous), unintended pregnancy after hormonal contraceptive failure (if the hormonal 
contraceptive was correctly used), ectopic pregnancy, fetal demise, or any congenital 
anomaly/birth defect of the baby. Those SAEs must be additionally reported using the 
Investigator SAE Report form.
11.1.7
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the Drug Accountability or Study Drug Dosing module of the eCRF. Any SAE or 
nonserious AE associated with excessive dosing must be followed as any other SAE or 
nonserious AE. These events are only considered AEs or SAEs if there are associated clinical 
signs and symptoms or if the act of taking the excess medicine itself is an AE or SAE 
(eg, suicide attempt).
11.1.8
Safety signal detection
Selected data from this study will be reviewed periodically, at least quarterly, to detect as early 
as possible any safety concern(s) related to the IMP so that Investigators, clinical study subjects, 
regulatory authorities, and IECs will be informed appropriately and as early as possible.
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of relevant safety data, such as AEs, results of laboratory tests and technical and physical 
examinations.
Any findings from this review will be brought to the attention of the DMC, that will 
systematically monitor and report on the progress, safety, and/or critical efficacy endpoints of the 
study by convening to review the ongoing program safety and efficacy data. This includes 
evaluating the safety signals and benefit-risk balance for the study subjects in relationship with 
new data relevant for IMP efficacy and safety. The benefit-risk balance of every subject entering 
the study will be reviewed by the DMC within approximately 3 months after first dosing in 
EP0073. Voting members of the DMC will include external physicians with experience in 
treating refractory epilepsy and a cardiologist. The DMC will make recommendations to the 
company about continuation of the study, which may include changes to study procedures, or 
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termination of the clinical study. The precise membership, scope, and responsibilities of the 
DMC are described in the DMC Charter.
The Study Physician or medically qualified designee/equivalent will also conduct an ongoing 
reconciliation of SAEs and Pregnancy Reports between the safety and clinical databases, in 
collaboration with the PS representative.
11.2
Serious adverse events
11.2.1
Definition of serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:

Death

Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)

Significant or persistent disability/incapacity

Congenital anomaly/birth defect (including that occurring in a fetus)

Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious
(Important medical events may include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse.)

Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.)
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11.2.2
Procedures for reporting serious adverse events
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by 
the site (see contact information for SAE reporting listed in the Serious Adverse Event Reporting 
section at the front of the protocol). The Investigator must forward to UCB (or its representative) 
a duly completed “Investigator SAE Report Form for Development Drug” (SAE report form) 
provided by UCB, even if the data are incomplete, or if it is obvious that more data will be 
needed in order to draw any conclusions. Information recorded on this form will be entered into 
the global safety database.
An Investigator SAE report form will be provided to the Investigator. The Investigator SAE 
Report form must be completed in English. 
It is important for the Investigator, when completing the SAE report form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the Investigator is very important for UCB to consider in assessing the safety of the IMP 
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner.
Additional information (eg, autopsy or laboratory reports) received by the Investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE report form.
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the IMP), up to 
30 days from the end of the study for each subject, and to also inform participating subjects of 
the need to inform the Investigator of any SAE within this period. Serious AEs that the 
Investigator thinks may be associated with the IMP must be reported to UCB regardless of the 
time between the event and the end of the study.
Upon receipt of the SAE report form, UCB will perform an assessment of expectedness of the 
reported SAE. The assessment of the expectedness of the SAE is based on the Investigator’s 
Brochure.
11.2.3
Follow up of serious adverse events
An SAE should be followed until it has resolved, has a stable sequelae, the Investigator
determines that it is no longer clinically significant, or the subject is lost to follow up. 
Information on SAEs obtained after clinical database lock will be captured through the PS
database without limitation of time.
11.3
Adverse events of special interest
An AE of special interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, 
must ALWAYS be reported to UCB as an AE of special interest (ie, without waiting for any 
additional etiologic investigations to have been concluded). Follow-up information should then 
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be reported if an alternative etiology is identified during investigation and monitoring of the 
subject. Guidance on the evaluation and management of PDILI is provided in Section 11.6.1.
11.4
Immediate reporting of adverse events
The following AEs must be reported immediately:

SAE: AE that the Investigator classifies as serious by the above definitions regardless of 
causality

Suspected transmission of an infectious agent via a medicinal product

Adverse events of special interest (see Section 11.3)
11.5
Anticipated serious adverse events
The following list of Anticipated SAEs has been identified, as these events are anticipated to 
occur in the population studied in this protocol at some frequency that is independent of drug 
exposure. This original list will remain in effect for the duration of the protocol.
This list does not change the Investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 11.2.2.
Table 11‒1: Anticipated SAEs for the epilepsy population
MedDRA System Organ Class
MedDRA Preferred Term
Congenital, familial, and genetic disorders
Teratogenicity
General disorders and administration site disorders
Sudden unexplained death in epilepsy
Injury, poisoning, and procedural complication
Falla, fracturea, injurya
Nervous system disorders
Cluster seizures, cognitive disorder, convulsion,
incontinencea, b, status epilepticus
Pregnancy, puerperium, and perinatal disorders
Abortion spontaneous
Psychiatric disorders
Abnormal behavior, anxiety, confusional state, 
psychotic behavior, sleep disorder
Reproductive system and breast disorders
Impotence, menstrual disorder
MedDRA=Medical Dictionary for Regulatory Activities; SAE=serious adverse event; SOC=System Organ Class
a Event is considered to be anticipated when occurring in context of sezure. 
b Event is not classified in MedDRA primary SOC. 
11.6
Laboratory measurements
The following laboratory parameters will be measured at the scheduled time points presented in 
Table 5‒2:
Table 11‒2: Laboratory measurements
Hematology
Chemistry
Urinalysis
a
Basophils
ALP
Total protein
Eosinophils
Calcium
Glucose
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Table 11‒2: Laboratory measurements
Hematology
Chemistry
Urinalysis
a
Lymphocytes
Chloride
pH
Monocytes
Magnesium
RBC
Neutrophils
Potassium
WBC
Hematocrit
Sodium
Hemoglobin
Glucose
MCH
BUN or urea
MCHC
AST
MCV
ALT
Platelet count
Total bilirubin
RBC count
LDH
WBC count
Creatinine
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood 
urea nitrogen; LDH=lactate dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular 
hemoglobin concentration; MCV=mean corpuscular volume; RBC=red blood cell; WBC=white blood cell
a Dipstick test only
Also, a drug and alcohol screen (amphetamines, benzodiazepines, barbiturates, cocaine, 
cannabinoids, methadone, opiates, and alcohol) will be performed at the scheduled time points 
presented in Table 5‒2.
In addition, for females of childbearing potential, a serum pregnancy test and a urine pregnancy 
test (beta-human chorionic gonadotropin) will be performed at the scheduled time points 
presented in Table 5‒2.
11.6.1
Evaluation of PDILI
The PDILI IMP discontinuation criteria for this study are provided in Section 6.3.1, with the 
accompanying required follow-up investigation and monitoring detailed below. All PDILI events 
must be reported as an AE and reported to the study site and Sponsor within 24 hours of learning 
of their occurrence. Any PDILI event that meets the criterion for potential Hy’s Law must be 
reported as an AE of special interest (see Section 11.3), and, if applicable, also reported as an 
SAE (see Section 11.1.1). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 11‒3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 11.6.1.1). The local 
hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. Additional investigation and monitoring may be required and adapted based 
on the diagnosis after the cause of the liver injury/abnormality is confirmed (details in 
Section 11.6.1.4). 
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The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and Sponsor.
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result.
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 
2 laboratory tests are significantly different. Data from the local and central laboratory are to be 
recorded on the applicable eCRF pages.
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the Investigator should also 
consider dose reduction for medically necessary concomitant medication and consider changing 
any medically required concomitant medication known to be hepatotoxic to a suitable 
alternative.
When IMP is stopped due to PDILI (as described in Section 6.3.1), IMP must be permanently 
discontinued unless a subsequent alternative diagnosis fully explains the hepatic findings. If a 
subsequent alternative diagnosis fully explains the hepatic findings, and the requirements 
provided in Section 11.6.1.2.1 are met, rechallenge with IMP may be appropriate. 
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
The table below summarizes the approach to investigate PDILI.
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Table 11‒3: Required investigations and follow up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consult.c
Medical Monitor 
must be notified 
within 24 hours 
(eg, by laboratory 
alert) and subject 
discussed with 
Medical Monitor 
ASAP.
Immediate, 
permanent IMP 
discontinuation.
Essential: Must 
have repeat liver 
chemistry values 
and additional 
testing completed 
ASAP (see 
Section 11.6.1.3); 
recommended to 
occur at the site 
with HCP.
Monitoring of liver chemistry 
values at least twice per week 
until values normalize, stabilize, 
or return to within baseline 
values.d
≥8xULN
NA
NA
≥3xULN
NA
Yes
Immediate, 
temporary or 
permanent, IMP 
discontinuation.
≥3xULN 
(and ≥2x 
baseline) 
and 
<5xULN
<2xULN
No
Discussion with 
Medical Monitor 
required if the 
criterion that allows 
for IMP continuation 
is met.
Further investigation 
– immediate IMP 
discontinuation not 
required (see 
Section 11.6.1.2).
Not required 
unless otherwise 
medically 
indicated (at 
discretion of the 
Investigator).
≥5xULN 
(and ≥2x 
baseline) 
<2xULN
No
Discussion with 
Medical Monitor 
required.
Immediate, 
permanent IMP 
discontinuation.
Essential: Every 
attempt must be 
made to have 
repeat liver 
chemistry values 
and additional 
testing completed 
within 48 hours 
at the site with 
HCP (see 
Section 11.6.1.3).
Monitoring of liver chemistry 
values at least twice per week 
until values normalize, stabilize, 
or return to within baseline 
values.d
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Table 11‒3: Required investigations and follow up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug-induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause).
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor.
c Details provided in Section 11.6.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of 
potential hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
d Unless an alternative monitoring schedule is agreed by the Investigator and UCB responsible physician. Determination of stabilization is at the discretion of 
the Investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
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11.6.1.1
Consultation with the Medical Monitor and local hepatologist
Potential drug-induced liver injury events require notification of the Medical Monitor within 
24 hours (eg, by laboratory alert), and the subject must be discussed with the Medical Monitor as 
soon as possible. If required, the subject must also be discussed with the local hepatologist. The 
local hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. If determined necessary, this discussion should be followed by a full 
hepatology assessment (see Section11.6.1.3) and SAE report (if applicable).
11.6.1.2
Immediate action: determination of IMP discontinuation
All PDILI events require immediate action, testing, and monitoring. 
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 11‒3 for details).
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. The Investigator should also consider dose 
reduction for medically necessary concomitant medication and consider changing any medically 
required concomitant medication known to be hepatotoxic to a suitable alternative.
11.6.1.2.1
IMP restart/rechallenge (if applicable)
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
Subjects who are immediately discontinued from IMP due to having met certain criteria for 
PDILI (as described in Section 6.3.1 and Table 11‒3), but for whom an alternative diagnosis is 
confirmed, can rarely restart IMP. Rechallenge with IMP can occur only if ALL of the following 
requirements are met:

The results of additional testing and monitoring described in Section 11.6.1.3 and 
Section 11.6.1.4 confirm a nondrug-related cause for the abnormal hepatic laboratory 
parameters and any associated symptoms (ie, a subsequent alternative diagnosis fully 
explains the hepatic findings). 

No alternative treatment options are available to the subject.

The subject has shown clear therapeutic benefit from the IMP.

Subject’s ALT or AST elevations do not exceed ≥3xULN.

Subject’s total bilirubin is <1.5xULN.

Subject has no signs or symptoms of hypersensitivity. 

The rechallenge is approved by the UCB responsible physician and a hepatologist. The 
hepatologist must be external to UCB. It is recommended that the hepatologist be a local 
hepatology expert or the hepatologist treating the subject.

Subject agrees to the Investigator-recommended monitoring plan.
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11.6.1.3
Testing: identification/exclusion of alternative etiology
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that they may have been caused by the IMP are detailed in 
Table 11‒4 (laboratory measurements) and Table 11‒5 (additional information). Results of the 
laboratory measurements and information collected are to be submitted to the Sponsor on the 
corresponding eCRF. If the medical history of the subject indicates a requirement for other 
assessments not included below, these additional assessments should be completed and 
submitted, as applicable.
All blood samples should be stored, if possible. If tests are done locally for more rapid results, a 
concurrent sample must also be sent to the central laboratory.
The following measurements are to be assessed:
Table 11‒4: PDILI laboratory measurements
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain heterophile 
antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screen
Chemistry
Amylase
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase elevation
Additional
Prothrombin time/INRa
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; CPK=creatine phosphokinase; HBcAb-IgM=hepatitis B core antibody-IgM; 
HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate 
dehydrogenase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic acid; 
ULN=upper limit of normal
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Table 11‒4: PDILI laboratory measurements
a
Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; 
hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative cause).
The following additional information is to be collected: 
Table 11‒5: PDILI information to be collected
New or updated information
Concomitant prescription and over-the-counter medications (eg, acetaminophen, herbal remedies, 
vitamins); dosages and dates should be included.
Pertinent medical history, including the following:

History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty 
liver disease”)

Adverse reactions to drugs

Allergies

Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 antitrypsin 
deficiency)

Recent travel 

Progression of malignancy involving the liver (Note: Metastatic disease to the liver, by itself, 
should not be used as an explanation for significant AST and/or ALT elevations.)
The appearance or worsening of clinical symptoms of hepatitis or hypersensitivity (eg, fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, decreased appetite, abdominal pain, jaundice, fever, or 
rash)
Recent clinically significant hypotension or hypoxemia with compromised cardiopulmonary function
Alcohol and illicit drug use
Results of liver imaging or liver biopsy, if done
Results of any specialist or hepatology consult, if done
Any postmortem/pathology reports
ALT=alanine aminotransferase; AST=aspartate aminotransferase; PDILI=potential drug-induced liver injury
11.6.1.4
Follow-up evaluation
Potential drug-induced liver injury events require follow-up and monitoring as described in 
Table 11‒3. Monitoring should continue until liver chemistry values normalize, stabilize, or 
return to baseline. Determination of stabilization is at the discretion of the Investigator in 
consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
11.7
Other safety measurements
11.7.1
Vital signs
Vital signs will be measured at the scheduled time points presented in Table 5‒2.
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Vital signs including pulse rate, systolic BP, diastolic BP, and RR will be measured in supine 
position, after 5 minutes of rest. Any clinically significant abnormality in the view of the 
Investigator will be recorded as an AE.
11.7.2
Electrocardiogram
The 12-lead ECG recordings will be measured at the scheduled time points presented in 
Table 5‒2.
All ECG recordings will be performed with the subject resting in the supine position for at least 
5 minutes. ECG will be recorded at a speed of 25mm/s and with a calibration of 1cm/mV.
The Investigator should review all ECG recordings and, if there are abnormalities that are 
considered clinically significant for a particular subject, then the Investigator should initiate a 
review by a specialist of all ECG data pertaining to that subject. The following ECG parameters 
will be recorded in the eCRF: heart rate, PR interval, QRS duration, QT interval, QTcB or QTcF, 
and Investigator’s conclusion on ECG profile.
11.7.3
Echocardiogram
Echocardiograms will be recorded at the scheduled time points presented in Table 5‒2. A 
complete echocardiography manual will be provided separately.
2-Dimensional Doppler echocardiography will be performed with:
1. Diastolic measurements (mitral forward flow E and A waves and deceleration time)
2. Tissue Doppler on medial and lateral mitral valve annulus (S, E, and A waves)
3. Standardized views for left atrial volume measurements.
Images will be recorded and stored digitally and retained if further analysis is needed. In the 
event that echocardiograms are not interpretable during the study, alternative assessments using 
either transesophageal echocardiography or cardiac magnetic resonance imaging (CMR) should 
be performed. Central reading of the echocardiograms may be performed by a specialized 
vendor.
In case of cardiac TEAEs associated with echocardiographic findings, the subject must be 
withdrawn from the study if the finding is clinically concerning or worsens over time, and the 
following should be completed:

The subject should return for an EDV

The subject should immediately stop the intake of UCB0942 or be down titrated as instructed 
at the EDV

SFUs should be scheduled 1 week and 30 days after the subject has discontinued UCB0942
These TEAEs should be followed up at least 6 months or until they have resolved, have a stable 
sequelae, or the subject is lost to follow up.
11.7.4
Physical and neurological examination
Physical and neurological examinations will be performed at the scheduled time points presented 
in Table 5‒2. The complete physical examination will include general appearance; ear, nose, and 
throat; eyes, hair, and skin; respiratory; cardiovascular; gastrointestinal; musculoskeletal; 
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hepatic; and mental status. The brief physical examination will include review of the following 
body systems: cardiovascular, pulmonary, abdominal (hepato-gastrointestinal), and 
dermatologic.
The complete neurological examination will include a selected assessment of the following: 
general (level of consciousness, mental status, speech, reasoning, mood), cranial nerves, reflexes, 
motor system (general, muscle strength, muscle tone), coordination/cerebellar function (eye 
movements, walking, stance, limb ataxia), and sensation. The brief neurological examination will 
include a selected assessment of the following: cognition, general, reflexes, muscle strength, and 
coordination/cerebellar function.
Findings that are considered clinically significant changes since the physical or neurological 
examination at the EV will be recorded as AEs.
Body weight will be measured at the scheduled time points presented in Table 5‒2. Body weight 
will be measured with the subject in underwear or light clothing and without wearing shoes; the 
outcome will be rounded to the nearest 0.1kg. At the EV, the BMI will be calculated (weight 
[kg]/[height (m)]²) and will be reported to 1 decimal place.
11.7.5
Assessment of suicidality
Suicidality will be assessed by trained study personnel using the C-SSRS (Posner et al, 2011). 
This scale will be used at screening for the EP0069 study as well as to assess suicidal ideation 
and behavior that may occur during the current study. The C-SSRS will be completed at the 
scheduled time points presented in Table 5‒2.
11.7.6
Psychiatric and cognitive assessments
The overall psychiatric condition of the subjects will be assessed using the BPRS questionnaire. 
The BPRS will be completed at the scheduled time points presented in Table 5‒2. The BPRS is a 
questionnaire completed by the Investigator or a delegate and consists of 18 questions which 
capture the psychiatric condition of the subject.
The MMSE is a sensitive, valid, and reliable 30-point questionnaire completed by the 
Investigator. The MMSE is used extensively in clinical and research settings to measure 
cognitive impairment. The MMSE will be completed at the scheduled time points presented in 
Table 5‒2.
Further details about all questionnaires used in this study and their administration will be covered 
in the Study Manual.
11.7.7
Monitoring symptoms of withdrawal
Any symptoms of withdrawal reactions will be monitored using the CIWA-B questionnaire. The 
CIWA-B will be completed at the scheduled time points presented in Table 5‒2. The CIWA-B 
questionnaire is completed by the subject and contains 22 questions which are selected to 
distinguish withdrawal symptoms from other symptoms. Further details about this questionnaire 
will be covered in the Study Manual.
11.7.8
Narratives of benefit and benefit-risk assessment
Narratives of benefit by the subject/caregiver and the benefit-risk statement and the justification 
by the Investigator will be captured in a dedicated form during the Screening Period and at other 
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scheduled time points presented in Table 5‒2. The verbatim of the attained benefits or treatment 
with UCB0942, including seizure control, health and well-being, and social functioning, declared 
by a subject/caregiver will be recorded as narratives by the Investigator or site personnel. The 
Investigator will also assess and provide a brief justification that the benefit-risk ratio for the 
subject on long-term treatment with the IMP supports continuation in the study, considering the 
knowledge of the IMP’s efficacy and safety profile and alternative treatment options.
12
STUDY MANAGEMENT AND ADMINISTRATION 
12.1
Adherence to protocol
The Investigator should not deviate from the protocol. However, the Investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IEC, or 
Sponsor.
After implementation of such measure, the Investigator must notify the Clinical Project Manager 
(CPM) of the Sponsor within 24 hours and follow any local regulatory requirements.
12.2
Monitoring
PRA will monitor the study to meet the PRA’s monitoring Standard Operating Procedures 
(SOPs), ICH-GCP guideline, and applicable regulatory requirements, and to ensure that study 
initiation, conduct, and closure are adequate. Monitoring of the study may be delegated by UCB 
to a CRO or a contract monitor.
The Investigator and his/her staff are expected to cooperate with PRA and to be available during 
the monitoring visits to answer questions sufficiently and to provide any missing information. 
The Investigators/institutions will permit direct access to source data/documents for study-related 
monitoring, audits, IEC review, and regulatory inspection(s).
The Investigator will allow PRA to periodically review all eCRFs and corresponding source 
documents (eg, hospital and laboratory records for each study participant). Monitoring visits will 
provide PRA with the opportunity to evaluate the progress of the study, verify the accuracy and 
completeness of eCRFs, ensure that all protocol requirements, applicable authorities regulations, 
and Investigator’s obligations are being fulfilled, and resolve any inconsistencies in the study 
records.
12.2.1
Definition of source data 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, or quality of life 
questionnaires, for example. Source documents should be kept in a secure, limited access area.
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Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the Investigator and become a permanent part of the subject’s source documents. The 
Investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent.
Electronic data records, such as echocardiogram results, must be saved and stored as instructed 
by UCB (or designee).
12.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 12.2.1.
12.3
Data handling
12.3.1
Case Report form completion
This study is performed using remote data capture. The Investigator is responsible for prompt 
reporting of accurate, complete, and legible data in the eCRFs and in all required reports.
Any change or correction to the eCRF after saving must be accompanied by a reason for the 
change.
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the Investigator.
The Investigator should maintain a list of personnel authorized to enter data into the eCRF.
Detailed instructions will be provided in the eCRF Completion Guidelines.
12.3.2
Database entry and reconciliation
Case Report forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used in addition to manual review to check for discrepancies and to ensure consistency of 
the data. The data are entered into the eCRF once and are subsequently verified.
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
12.3.3
Subject Screening and Enrollment log/Subject Identification Code list
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment 
Log.
The Investigator will keep a Subject Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each subject.
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The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
12.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, benefit-risk 
balance (0 to 4) indicating the risks outweigh the benefits, or unsatisfactory enrollment with 
respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
Investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IEC should also be informed and provided with reason(s) for the termination 
or suspension by the Sponsor or by the Investigator/institution, as specified by the applicable 
regulatory requirement(s). In addition, arrangements will be made for the return of all unused 
IMP and other material in accordance with UCB procedures for the study.
12.5
Archiving and data retention
The Investigator will maintain adequate records for the study, including eCRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data.
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). The Investigator will contact 
UCB for authorization prior to the destruction of any study records or in the event of accidental 
loss or destruction of any study records. The Investigator will also notify UCB should he/she 
relocate or move the study-related files to a location other than that specified in the Sponsor’s 
Study Master File.
12.6
Audit and inspection
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
study procedures) are appropriate for the study, and that all data relevant for the evaluation of the 
IMP have been processed and reported in compliance with the planned arrangements, the 
protocol, investigational site, and IEC SOPs, ICH GCP, and applicable regulatory requirements.
The Investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the Investigator will immediately 
inform UCB (or designee).
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12.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study.
13
STATISTICS
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP).
13.1
Definition of analysis sets
The Enrolled Set will consist of all enrolled subjects who have signed the Informed Consent 
form.
The Safety Set (SS) will consist of all enrolled subjects who took at least 1 dose of study 
medication.
The Full Analysis Set (FAS) will consist of all enrolled subjects who took at least 1 dose of study 
medication and completed at least 1 seizure diary during the Evaluation Period.
The Pharmacokinetic Per-Protocol Set will consist of subjects in the FAS who received at least 
1 dose of study medication, and did not have a major protocol deviation impacting the PK 
variables.
13.2
General statistical considerations
Descriptive statistics, such as the mean, standard deviation, median, minimum value, and 
maximum value for quantitative variables, and counts and percentages for categorical variables, 
will be provided. Key supporting data will be provided in data listings. Summary statistics will 
be presented by the overall UCB0942 group, unless otherwise indicated.
13.3
Planned safety analyses
The long-term safety of UCB0942 at individualized doses will be evaluated by means of the 
safety analyses. Summary tables will be presented over the study periods (Evaluation, Taper, and
Safety Follow-Up) by 3-month time intervals and by categories of total duration of exposure.
All safety variables will be analyzed by descriptive methods and listed on the SS.
Treatment-emergent AEs will be summarized by study period (Evaluation, Taper, and Safety 
Follow-Up) by 3-month time intervals and categories of total duration of exposure, using the
Medical Dictionary for Regulatory Activities (MedDRA®) primary System Organ Class (SOC) 
and Preferred Term in incidence tables. Separate tables will be provided for AEs leading to 
withdrawal from the study and SAEs overall and by the subcategories listed above.
Laboratory values, ECG data (heart rate, PR, QTc [using Bazett’s and Fridericia’s formula] and 
QRS), vital signs, and weight will be summarized by period and visit (actual values and change 
from baseline). Possible clinically significant treatment-emergent abnormalities for laboratory 
values, vital signs, and weight will be listed and summarized by period and visit. 
Electrocardiogram abnormalities will also be listed by period and visit.
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Summary tables (and graphical outputs if needed) will be performed on the Doppler 
echocardiography data.
Physical and neurological examinations, psychiatric assessments (BPRS), memory or cognition 
from the MMSE and the withdrawal symptoms using the CIWA-B assessment will be provided 
as listing by period and visit (actual values and change from baseline). C-SSRS results will be 
displayed in a listing.
Any additional listings or tabulations will be described in the SAP.
13.4
Planned efficacy analyses
In both this study and EP0069 only POS of type IA1, IB, and IC and not non-motor IA2, IA3 or 
IA4 seizures will be counted for the assessment of seizure frequency and responder rate. For 
assessment of seizure-free rate and days, all seizure types will be considered.
13.4.1
Analysis of the primary efficacy variable
The primary efficacy variable is the 75%RR by 3-month intervals over the Evaluation Period; it 
will be summarized with descriptive statistics. A 75% responder is defined as a subject with a 
≥75% reduction in POS frequency relative to the 2-week Prospective Outpatient Baseline Period 
defined in EP0069. Seizure frequency will be standardized to a 28-day duration. Potential 
sensitivity analyses of the primary efficacy variable will be described in the SAP.
13.4.2
Analysis of the secondary efficacy variables
The following secondary efficacy variables will be summarized with descriptive statistics:

POS frequency per 28 days by 3-month intervals over the Evaluation Period of the EP0073 
study; the median will be considered as the key statistic.

POS frequency per 28 days by seizure type by 3-month intervals over the Evaluation Period 
of the EP0073 study; the median will be considered as the key statistic.

Percent reduction in POS frequency relative to the 2-week Prospective Outpatient Baseline 
Period defined in EP0069 by 3-month intervals over the Evaluation Period of the EP0073 
study.

50% RR by 3-month intervals over the Evaluation Period of the EP0073 study. A 50% 
responder is defined as a subject with a ≥50% reduction in POS frequency relative to the 
2-week Prospective Outpatient Baseline Period defined in EP0069.

Percentage of seizure-free days by 3-month intervals over the Evaluation Period.

Seizure-free rate by 3-month intervals over the Evaluation Period.

Changes in QOLIE-31-P scores from V3 of EP0069 through the assessment of the 
Evaluation Period.
13.5
Planned pharmacokinetic analyses
Plasma concentrations of UCB0942 and metabolites will be listed and summarized using 
descriptive statistics.
The PK samples will be taken to inform subject compliance, in addition to refinement of the 
UCB0942 population PK modeling. Exploratory population PK analysis will be performed 
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together with evaluation of longer-term (up to 1 year) exposure-response relationships to support 
the understanding of the clinical efficacy profile of UCB0942.
13.6
Handling of protocol deviations
After all data have been verified/entered into a database and prior to database lock, a data 
evaluation meeting will take place. The purpose of the data evaluation will be to examine all 
protocol deviations and to verify the quality of the data. The data evaluation will also help in 
guiding decisions on how to manage data issues on a case-by-case basis (eg, withdrawals, 
dropouts, and protocol deviations).
Accepted deviations from theoretical time points will be described in the appropriate documents 
and included in the Study Master File. After the data review, resolution of all issues, and 
documentation of all decisions, the database will be locked.
13.7
Handling of dropouts or missing data
The methods for handling dropouts will be described in the SAP. Safety and efficacy variables 
will be analyzed as they are available. Days with missing information will be ignored in the 
calculation of the seizure frequency. Since subjects will drop out at different times from the 
study, results will be presented by categories of duration of exposure.
13.8
Planned interim analysis and data monitoring
A DMC will systematically monitor and report (at least quarterly up to the time point when the 
last patient entering EP0073 reaches 1 year in the study, and less frequent thereafter) on the 
progress, safety, and/or critical efficacy endpoints of this study by convening to review the 
ongoing program safety and efficacy data. This includes evaluating the safety signals and 
benefit-risk balance for the study subjects in relationship to new data relevant for IMP efficacy 
and safety. The benefit-risk balance of every subject entering the study will be reviewed by the 
DMC approximately 3 months after first dosing in EP0073. Blinded data until database lock 
from EP0069 and data from the OLE EP0073 studies will be reviewed in order for the DMC to 
provide an ongoing risk-benefit evaluation with particular reference to the occurrence of 
psychiatric and cardiological/cardiovascular AEs, seizure control, and any new identified safety 
signals. Voting members of the DMC will include external physicians with experience in treating 
refractory epilepsy and a cardiologist, none of whom will be involved with the conduct of the 
study, either by management or participation. In addition, there will be an independent reporting 
team, consisting of an independent statistician and independent statistical programmers, who will 
be completely independent from the blinded reporting team. The blinded reporting team will be 
responsible for all operational aspects of the study, including routine monitoring and cleaning of 
the data, programming, and quality control of all analyses defined in the interim EP0073 SAP on 
blinded data of EP0069 and unblinded data of EP0073 (open-label study). If required for 
monitoring of safety and benefit-risk of EP0073 patients, unblinded data from EP0069 study can 
be reviewed by the external members of the DMC at closed sessions and provided by an 
independent statistician. The DMC will make recommendations to the company, which may 
include changes to study procedures, or termination of the clinical study. 
A DMC Charter will define the composition, roles, and responsibilities of the DMC, specify the 
data to be reviewed and the periodicity of data review, and determine the procedures to be 
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followed to maximize subject safety and ensure that the benefit-risk balance justifies 
participation in the study. 
The narratives of benefit attained with UCB0942 treatment and the Investigator’s justification for 
the concluded benefit-risk balance will be among the data reviewed by the DMC.
13.9
Determination of sample size
For this OLE study, no sample size calculation is needed. The sample size will depend upon 
recruitment into and completion of the previous study. It is estimated that about 40 subjects from 
EP0069 will enter this EP0073 study.
14
ETHICS AND REGULATORY REQUIREMENTS
14.1
Informed consent
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the subject in both oral and written form by the Investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the Investigator.
Prior to participation in the study, the written Informed Consent form should be signed and 
personally dated by the subject, or his/her legal representative, and by the person who conducted 
the informed consent discussion (Investigator or designee). The subject or his/her legal 
representative must receive a copy of the signed and dated Informed Consent form. As part of 
the consent process, each subject must consent to direct access to his/her medical records for 
study-related monitoring, auditing, IEC review, and regulatory inspection.
If the Informed Consent form is amended during the study, the Investigator (or the Sponsor, if 
applicable) must follow all applicable regulatory requirements pertaining to the approval of the 
amended Informed Consent form by the IEC and use of the amended form.
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the Informed Consent form. An eCRF 
must not be started, nor may any study specific procedure be performed for a given subject, 
without having obtained his/her written consent to participate in the study.
14.2
Subject identification cards
Upon signing the Informed Consent and Assent form (as applicable), the subject and/or caregiver 
will be provided with a subject identification card in the language of the subject. The Investigator
will fill in the subject identifying information and medical emergency contact information. The 
Investigator will instruct the subject to keep the card with him/her at all times.
14.3
Independent Ethics Committees
The study will be conducted under the auspices of an IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki.
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UCB (or its representative) will ensure that an appropriately constituted IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, UCB (or its representative) will forward copies of the protocol, Informed 
Consent form, Investigator’s Brochure, Investigator’s curriculum vitae (if applicable), 
advertisement (if applicable), and all other subject-related documents to be used for the study to 
the IEC for its review and approval.
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IEC for the protocol.
UCB (or its representative) will promptly report to the IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects.
The Investigator will not make any changes in the study or study conduct without IEC approval, 
except where necessary to eliminate apparent immediate hazards to the subjects. For minor 
changes to a previously approved protocol during the period covered by the original approval, it 
may be possible for the Investigator to obtain an expedited review by the IEC as allowed.
As part of the IEC requirements for continuing review of approved studies, UCB (or its 
representative) will be responsible for submitting periodic progress reports to the IEC (based on 
IEC requirements), at intervals appropriate to the degree of subject risk involved, but no less than 
once per year. UCB (or its representative) should provide a final report to the IEC following 
study completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active Investigators in accordance with applicable regulatory requirements. 
The appropriate IEC will also be informed by the Investigator or the Sponsor, as specified by the 
applicable regulatory requirements in each concerned country. Where applicable, Investigators 
are to provide UCB (or its representative) with evidence of such IEC notification.
14.4
Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number.
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
subject’s primary medical records that directly concerns this study (including, but not limited to, 
laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study).
14.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
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Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IEC, and the regulatory authorities (if required), prior to being 
implemented.
15
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements, as applicable.
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16
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Loganathan MA, Enja M, Lippmann S. FORCED NORMALIZATION: Epilepsy and Psychosis 
Interaction. Innov Clin Neurosci. 2015; 12(5-6): 38–41. 
Mohanraj R, Brodie MJ. Diagnosing refractory epilepsy: response to sequential treatment 
schedules. Eur J Neurol. 2006;13(3):277-82.
Overall JE, Gorham DR. The brief psychiatric rating scale. Psychological Reports. 
1962:10:799-812.
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Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia-
Suicide Severity Rating Scale: initial validity and internal consistency findings from three 
multisite studies with adolescents and adults. Am J Psychiatry. 2011;168:1266-77.
Schiller Y, Najjar Y. Quantifying the response to antiepileptic drugs: effect of past treatment 
history. Neurology. 2008;70(1):54-65.
Sperling MR. The consequences of uncontrolled epilepsy. CNS Spectr. 2004;9(2):98-109.
Taylor DC, McMacKin D, Staunton H, Delanty N, Phillips J. Patients’ aims for epilepsy surgery: 
desires beyond seizure freedom. Epilepsia. 2001;42(5):629-33.
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17
APPENDICES
17.1
Protocol Amendment 1
Rationale for the amendment

Addition of a UCB0942 100mg (50mg bid) maintenance dose to allow Investigators the 
ability to explore the range of doses from 100mg to 800mg per day using bid dosing.

Addition of a UCB0942 25mg tablet, which was not previously available.

Addition of PK blood samples for measurement of plasma concentration of UCB0942 and 
metabolites at V3, V4, V5, V6, V7, V8, and V9. These samples will be taken to monitor 
subject compliance, amongst others. Exploratory population PK analysis will be performed 
together with evaluation of longer-term (up to 1 year) exposure-response relationships to 
support the understanding of the clinical efficacy profile of UCB0942.

Change of V21 from M60 to M58. The study duration has been reduced to ensure adequate 
insurance coverage in case of unplanned extension of study participation of single subjects 
for safety reasons.

Added that there will be no tapering from the EP0069 dose before the first dose is 
administered in EP0073.

Changed text to clarify that narratives of benefit and benefit-risk assessment can be captured
during the Screening Period, thus from V1 to V2.

Change of the withdrawal criterion on suicidal ideation.

Change of Clinical Trial Biostatistician.

Addition of Enrolled Set.

Minor textual changes or additions, and correction of typos.
Modifications and changes
Specific changes
Change #1
Section Study Contact Information, Clinical Project Manager
Has been changed to:
Dr. 
Change #2
Section Study Contact Information, Clinical Trial Biostatistician
Name:
Address: UCB Biopharma SPRL
Chemin du Foriest
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B-1420 Braine-l'Alleud
BELGIUM
Phone:
Fax:
Has been changed to:
Name:
Address: UCB Biosciences Inc.
P.O. Box 110167
Research Triangle Park, NC 27709
USA
Phone:
Fax:
Change #3
Section List of Abbreviations
PK
pharmacokinetic(s)
Has been added
Change #4
Section 1 Summary, first bullet of first bullet list
The Investigator will also provide a statement and a brief justification of positive benefit-risk 
balance for each subject’s participation in EP0073 and long-term treatment with UCB0942 at 
V1.
Has been changed to:
During the Screening Period, the Investigator will also provide a statement and a brief 
justification of positive benefit-risk balance for each subject’s participation in EP0073 and 
long-term treatment with UCB0942.
Change #5
Section 1 Summary, second bullet of first bullet list
An Evaluation Period of up to 5 years, which will start with V2, the Entry Visit (EV), which is 
the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of EP0069.
Has been changed to:
An Evaluation Period of up to approximately 5 years, which will start with V2, the Entry Visit 
(EV), which is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of 
EP0069.
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Change #6
Section 1 Summary, first paragraph after first bullet list
They will continue this dose in the current study; however, throughout the Evaluation Period, the 
Investigator will be allowed to increase or decrease the dose of UCB0942 to optimize tolerability
and seizure control for each subject.
Has been changed to:
They will continue this dose in the current study and there will be no tapering from the EP0069 
dose before they receive the first dose in EP0073; however, throughout the Evaluation Period, 
the Investigator will be allowed to increase or decrease the dose of UCB0942 to optimize 
tolerability and seizure control for each subject.
Change #7
Section 1 Summary, first paragraph after first bullet list
Daily UCB0942 doses during this study may be 200mg (100mg bid), 400mg (200mg bid), 
600mg (300mg bid), or 800mg (400mg bid); intermediate doses will not be allowed except for 
tapering. The dose of UCB0942 must always be administered as bid morning and evening doses, 
approximately 12 hours apart, except for the 100mg daily dose which is administered as a 100mg 
tablet once daily during the Taper Period.
Has been changed to:
Daily UCB0942 doses during this study may be 100mg (50mg bid), 200mg (100mg bid), 400mg 
(200mg bid), 600mg (300mg bid), or 800mg (400mg bid); intermediate doses will not be allowed 
except for tapering and titration. The dose of UCB0942 must always be administered as bid 
morning and evening doses, approximately 12 hours apart. The first dose of the current study 
will be the dose on the evening of V2.
Change #8
Section 1 Summary, sixth paragraph after first bullet list
The primary objective of this study is to evaluate the long-term safety and tolerability of 
UCB0942 at individualized doses between 200mg/day to a maximum of 800mg/day in subjects 
with highly drug-resistant focal epilepsy.
Has been changed to:
The primary objective of this study is to evaluate the long-term safety and tolerability of 
UCB0942 at individualized doses between 100mg/day to a maximum of 800mg/day in subjects 
with highly drug-resistant focal epilepsy.
Change #9
Section 1 Summary, sixth paragraph after first bullet list
The exploratory objective is to evaluate the plasma concentrations of UCB0942 and metabolites.
Has been added
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Change #10
Section 1 Summary, last paragraph
Secondary efficacy variables are described in Section 4.2.2.
Has been changed to:
Secondary efficacy variables are described in Section 4.2.2 and the exploratory pharmacokinetic 
(PK) variable is described in Section 4.3.
Change #11
Section 2.3 Risks and mitigation strategy, first paragraph
In addition there are 7 important potential risks; some are specific to UCB0942 and were 
identified from the nonclinical and clinical databases (potential for: dependence, cardiac 
arrhythmia, hepatotoxicity and decreased growth) while the others are class effects (potential for: 
abuse, suicidality, worsening seizures).
Has been changed to:
In addition there are 7 important potential risks; some are specific to UCB0942 and were 
identified from the nonclinical and clinical databases (potential for: withdrawal/dependence, 
cardiac arrhythmia, hepatotoxicity and decreased growth) while the others are class effects 
(potential for: abuse, suicidality, worsening seizures).
Change #12
Section 2.3.1 Cardiac adverse events, first paragraph
A cardiologist concluded that the potential cardiac hazard of UCB0942 in humans is likely 
minimal; however, it is possible that epicardial or valvular changes will occur in humans with 
prolonged exposure (beyond 3 months).
Therefore, in this study, subjects will have an echocardiogram at Visit 1 and every 3 months for 
the first year and second year of treatment, and every 6 months in subsequent years to ensure 
early detection of any valvular or pericardial changes that may occur.
Has been changed to:
A cardiologist concluded that the potential cardiac hazard of UCB0942 in humans is likely 
minimal; however, it is possible that epicardial or valvular structural changes will occur in 
humans with prolonged exposure (beyond 3 months).
Therefore, in this study, subjects will have an echocardiogram at Visit 2 and every 3 months for 
the first year and second year of treatment, and every 6 months in subsequent years to ensure 
early detection of any valvular or pericardial changes that may occur.
Change #13
Section 3.1 Primary objective
To evaluate the long-term safety and tolerability of UCB0942 at individualized doses between 
200mg/day to a maximum of 800mg/day in subjects with highly drug-resistant focal epilepsy.
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Has been changed to:
To evaluate the long-term safety and tolerability of UCB0942 at individualized doses between 
100mg/day to a maximum of 800mg/day in subjects with highly drug-resistant focal epilepsy.
Change #14
Section 3.3 Exploratory objective has been added, with the objective as 
follows:
To evaluate the plasma concentrations of UCB0942 and metabolites.
Change #15
Section 4.3 Exploratory pharmacokinetic variable has been added, with the 
variable as follows:
Plasma concentrations of UCB0942 and metabolites during the first 13 months of treatment in 
EP0073.
Change #16
Section 5.1 Study description, first bullet of first bullet list
The Investigator will also provide a statement and a brief justification of positive benefit-risk 
balance for each subject’s participation in EP0073 and long-term treatment with UCB0942 at 
V1.
Has been changed to:
During the Screening Period, the Investigator will also provide a statement and a brief 
justification of positive benefit-risk balance for each subject’s participation in EP0073 and 
long-term treatment with UCB0942.
Change #17
Section 5.1 Study description, second bullet of first bullet list
An Evaluation Period of up to 5 years, which will start with V2, the EV, which is the same as 
V15 (Day OP57) of the 8-week Outpatient Maintenance Period of EP0069.
Has been changed to:
An Evaluation Period of up to approximately 5 years, which will start with V2, the EV, which is 
the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of EP0069.
Change #18
Section 5.1 Study description, first paragraph after first bullet list
They will continue this dose in the current study; however, throughout the Evaluation Period, the 
Investigator will be allowed to increase or decrease the dose of UCB0942 to optimize tolerability
and seizure control for each subject.
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Has been changed to:
They will continue this dose in the current study and there will be no tapering from the EP0069 
dose before they receive the first dose in EP0073; however, throughout the Evaluation Period, 
the Investigator will be allowed to increase or decrease the dose of UCB0942 to optimize 
tolerability and seizure control for each subject.
Change #19
Section 5.1 Study description, first paragraph after first bullet list
Daily UCB0942 doses during this study may be 200mg (100mg bid), 400mg (200mg bid), 
600mg (300mg bid), or 800mg (400mg bid); intermediate doses will not be allowed except for 
tapering. The dose of UCB0942 must always be administered as bid morning and evening doses, 
approximately 12 hours apart, except for the 100mg daily dose which is administered as a 100mg 
tablet once daily during the Taper Period.
Has been changed to:
Daily UCB0942 doses during this study may be 100mg (50mg bid), 200mg (100mg bid), 400mg 
(200mg bid), 600mg (300mg bid), or 800mg (400mg bid); intermediate doses will not be allowed 
except for tapering and titration. The dose of UCB0942 must always be administered as bid 
morning and evening doses, approximately 12 hours apart. The first dose of the current study 
will be the dose on the evening of V2.
Change #20
Section 5.2 Visit schedule
In the study visit schedule (Table 5‒1), M60 has been replaced by M58 and LEVP has been 
corrected to LEPV. 
Change #21
Section 5.3 Schedule of study assessments
In the schedule of study assessments (Table 5‒2), M60 has been replaced by M58. 
Change #22
Section 5.3 Schedule of study assessments
In the schedule of study assessments (Table 5‒2), the X for narratives of benefit and benefit-risk 
assessment has been moved from V1 to V2. Also the following footnote has been added:
i
Narratives of benefit and benefit-risk assessment can be completed any time during the 
Screening Period after obtaining informed consent and before eligibility check at V2.
Change #23
Section 5.3 Schedule of study assessments
In the schedule of study assessments PK blood sampling has been added, including a footnote:
k
Obtain blood samples for measurement of plasma concentration of UCB0942 and 
metabolites at V3, V4, V5, V6, V7, V8 and V9.
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Change #24
Section 5.4 Rationale for study design and selection of dose, last 
paragraph
Daily UCB0942 doses during this study may be 200mg (100mg bid), 400mg (200mg bid), 
600mg (300mg bid), or 800mg (400mg bid); intermediate doses will not be allowed except for 
tapering.
Has been changed to:
Daily UCB0942 doses during this study may be 100mg (50mg bid), 200mg (100mg bid), 400mg 
(200mg bid), 600mg (300mg bid), or 800mg (400mg bid); intermediate doses will not be allowed 
except for tapering and titration.
Change #25
Section 6.3 Withdrawal criteria, criterion #4
4. Subject cannot tolerate the minimum UCB0942 dose of 100mg bid (200mg/day).
Has been changed to:
4. Subject cannot tolerate the minimum UCB0942 dose of 50mg bid (100mg/day).
Change #26
Section 6.3 Withdrawal criteria, criterion #12
12. 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 C-SSRS. The subject should be 
referred immediately to a Mental Healthcare Professional and must be withdrawn from the study.
Has been changed to:
12. Subject has active suicidal ideation without a specific plan as indicated by a positive response 
(“Yes”) to Question 4 of the “Since Last Visit” version of the C-SSRS. The subject should be 
referred immediately to a Mental Healthcare Professional and may be withdrawn from the study 
based upon the Investigator’s judgment of benefit/risk of continuing the subject in the study/on 
study medication. Subject has 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 C-SSRS. The 
subject should be referred immediately to a Mental Healthcare Professional and must be 
withdrawn from the study.
Change #27
Section 7.1 Description of investigational medicinal product(s)
The UCB0942 25mg tablet has been added to the table. 
In addition, the note below the table has been changed as described below.
Note: UCB0942 tablets will be provided in bottles, containing either 80 or 200 tablets for both 
100mg and 200mg dosage. Appropriate bottle size will be dispensed through the IRT system as 
per visit schedule and visit interval.
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Has been changed to:
Note: UCB0942 tablets will be provided in bottles, containing 135 tablets for the 25mg dosage 
and either 80 or 200 tablets for both the 100mg and 200mg dosage. Appropriate bottle size will 
be dispensed through the IRT system as per visit schedule and visit interval.
Change #28
Section 7.2 Treatments to be administered, first paragraph
They will continue this dose in the current study; however, throughout the Evaluation Period, the 
Investigator will be allowed to increase or decrease the dose of UCB0942 to optimize tolerability
and seizure control for each subject.
Has been changed to:
They will continue this dose in the current study and there will be no tapering from the EP0069 
dose before they receive the first dose in EP0073; however, throughout the Evaluation Period, 
the Investigator will be allowed to increase or decrease the dose of UCB0942 to optimize 
tolerability and seizure control for each subject.
Change #29
Section 7.2 Treatments to be administered, first paragraph
Daily UCB0942 doses during this study may be 200mg (100mg bid), 400mg (200mg bid), 
600mg (300mg bid), or 800mg (400mg bid); intermediate doses will not be allowed except for 
tapering. The dose of UCB0942 must always be administered as bid morning and evening doses, 
approximately 12 hours apart, except for the 100mg daily dose which is administered as a 100mg 
tablet once daily during the Taper Period.
Has been changed to:
Daily UCB0942 doses during this study may be 100mg (50mg bid), 200mg (100mg bid), 400mg 
(200mg bid), 600mg (300mg bid), or 800mg (400mg bid); intermediate doses will not be allowed 
except for tapering and titration. The dose of UCB0942 must always be administered as bid 
morning and evening doses, approximately 12 hours apart. The first dose of the current study 
will be the dose on the evening of V2.
Change #30
Section 7.2 Treatments to be administered
In the three-week taper schedule for UCB0942 (Error! Reference source not found.), the 
100mg maintenance dose has been added and the following footnote has been deleted:
b 100mg daily dose administered as a 100mg tablet once daily.
Change #31
Section 7.2 Treatments to be administered, first paragraph below Table 7‒2
During the Taper Period, the dose of UCB0942 must always be administered as bid morning and 
evening doses, approximately 12 hours apart, except for the 100mg daily dose which is 
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administered as a 100mg tablet once daily during the Taper Period. Only 100mg tablets are 
allowed to be used during the Taper Period.
Has been changed to:
During the Taper Period, the dose of UCB0942 must always be administered as bid morning and 
evening doses, approximately 12 hours apart.
Change #32
Section 7.3 Packaging
UCB0942 tablets will be provided in bottles, containing either 80 or 200 tablets for both 100mg 
and 200mg dosage. Appropriate bottle size will be dispensed through the IRT system as per visit 
schedule and visit interval.
Has been changed to:
UCB0942 tablets will be provided in bottles, containing 135 tablets for the 25mg dosage and 
either 80 or 200 tablets for both the 100mg and 200mg dosage. Appropriate bottle size will be 
dispensed through the IRT system as per visit schedule and visit interval.
Change #33
Section 8.2.1 Entry Visit
Narratives of benefit and benefit-risk assessment (if not performed at V1)
Has been added
Change #34
Section 8.2.3 Minimal Evaluation Visit
Blood sample for measurement of plasma concentration of UCB0942 and metabolites (only at 
V3, V4, V6, and V8)
Has been added
Change #35
Section 8.2.4 Full Evaluation Visit
Blood sample for measurement of plasma concentration of UCB0942 and metabolites (only at 
V5 and V7)
Has been added
Change #36
Section 8.2.5 Yearly Evaluation Visit and Early Discontinuation Visit
The YEVs are planned in M13 (V9), M25 (V13), M37 (V17), M49 (V19), and M60 (V21; also 
LEPV).
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Has been changed to:
The YEVs are planned in M13 (V9), M25 (V13), M37 (V17), M49 (V19), and M58 (V21; also 
LEPV).
Change #37
Section 8.2.5 Yearly Evaluation Visit and Early Discontinuation Visit
Blood sample for measurement of plasma concentration of UCB0942 and metabolites (only at 
V9)
Has been added
Change #38
Section 10.0 Assessment of Pharmacokinetics has been added, with the 
text as follows:
10.1 Sampling procedures
Blood samples for PK will be obtained at the scheduled time points presented in Table 5‒2.
Exact sampling times will be recorded in the eCRF.
Detailed information on the collection, storage, preparation, and shipping of samples will be 
presented in a Laboratory Manual.
10.2 Bioanalytical methods
Plasma concentrations of UCB0942 and metabolites 
 and 
 
will be determined using validated bioanalytical methods.
Change #39
Section 11.7.3 Echocardiogram, first paragraph after numbered list
Central reading of the echocardiograms may be performed by a specialized vendor.
Has been added
Change #40
Section 11.7.6 Psychiatric and cognitive assessments, first paragraph
The BPRS is a questionnaire completed by the Investigator or a delegate and consists of 16
questions which capture the psychiatric condition of the subject.
Has been changed to:
The BPRS is a questionnaire completed by the Investigator or a delegate and consists of 18 
questions which capture the psychiatric condition of the subject.
Change #41
Section 11.7.6 Psychiatric and cognitive assessments, third paragraph
Further details about all questionnaire used in this study will be covered in the Study Manual.
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Has been changed to:
Further details about all questionnaires used in this study and their administration will be covered 
in the Study Manual.
Change #42
Section 11.7.8 Narratives of benefit and benefit-risk assessment
Narratives of benefit by the subject/caregiver and the benefit-risk statement and the justification 
by the Investigator will be captured in a dedicated form at V1 and other scheduled time points 
presented in Table 5‒2.
Has been changed to:
Narratives of benefit by the subject/caregiver and the benefit-risk statement and the justification 
by the Investigator will be captured in a dedicated form during the Screening Period and at other 
scheduled time points presented in Table 5‒2.
Change #43
Section 12.4 Termination of study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
Has been changed to:
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, negative 
benefit-risk balance, or unsatisfactory enrollment with respect to quality or quantity.
Change #44
Section 13.1 Definition of analysis sets
The Enrolled Set will consist of all enrolled subjects who have signed the Informed Consent 
form.
Has been added
Change #45
Section 13.2 General statistical considerations
Descriptive statistics, such as the mean, standard deviation, median, 25th percentile, 75th
percentile, minimum value, and maximum value for quantitative variables, and counts and 
percentages for categorical variables, will be provided. Key supporting data will be provided in 
data listings. Summary statistics will be presented by the overall UCB0942 group, unless 
otherwise indicated. 
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Has been changed to:
Descriptive statistics, such as the mean, standard deviation, median, minimum value, and 
maximum value for quantitative variables, and counts and percentages for categorical variables, 
will be provided. Key supporting data will be provided in data listings. Summary statistics will 
be presented by the overall UCB0942 group, unless otherwise indicated.
Change #46
Section 13.4.1 Termination of study
The primary efficacy variable is the 75%RR by 3-month intervals over the Evaluation Period; it 
will be summarized with descriptive statistics. A 75% responder is defined as a subject with a 
≥75% reduction in POS frequency relative to the 2-week Prospective Outpatient Baseline Period 
defined in EP0069. Seizure frequency will be standardized to a 28-day duration. 
Has been changed to:
The primary efficacy variable is the 75%RR by 3-month intervals over the Evaluation Period; it 
will be summarized with descriptive statistics. A 75% responder is defined as a subject with a 
≥75% reduction in POS frequency relative to the 2-week Prospective Outpatient Baseline Period 
defined in EP0069. Seizure frequency will be standardized to a 28-day duration. Potential 
sensitivity analyses of the primary efficacy variable will be described in the SAP.
Change #47
Section 13.5 Planned pharmacokinetic analyses has been added, with the 
text as follows:
Plasma concentrations of UCB0942 and metabolites will be listed and summarized using 
descriptive statistics.
The PK samples will be taken to inform subject compliance, in addition to refinement of the 
UCB0942 population PK modeling. Exploratory population PK analysis will be performed 
together with evaluation of longer-term (up to 1 year) exposure-response relationships to support 
the understanding of the clinical efficacy profile of UCB0942.
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17.2
Protocol Amendment 2
Rationale for the amendment

To update the protocol information pertaining to potential drug-induced liver injury 
(exclusion criteria, withdrawal criteria, adverse events of special interest, and assessment of 
safety) based on new standard language which is being applied across all protocols at UCB. 
Note that these additions do not reflect a change in the known safety of the compound. 

Changed text to clarify when the DMC is to review the benefit-risk balance of subjects 
entering the study.

Changed text regarding psychiatric events to align with the updated Investigator’s Brochure.

The PRA Medical Monitor has been added to the UCB Study Physician as contact point for 
the sites where appropriate.

Added text to allow for exceptions in the daily UCB0942 doses after consultation with the 
UCB Study Physician or PRA Medical Monitor.

Increase in estimate of approximately number of subjects from EP0069 who will be included 
in EP0073 to approximately 40.

Removed text on additional contraceptive measures for the partners of male subjects, based 
on nonclinical data.

Added text to have information regarding surgical evaluation, working status, caregiver 
support, and supervision collected at the Entry Visit.

Changed text to clarify prohibited medications.

Changed text to clarify withdrawal actions for subjects developing
psychiatric/mood/behavioral signs or disturbances.

Change of Clinical Project Manager.

Additional IMP manufacturer included.

Minor textual changes or additions, and correction of typos.
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Modifications and changes
Specific changes
Change #1
Section Study Contact Information, Clinical Project Manager
Name:
Dr. 
Address:
UCB Biosciences GmbH
Alfred-Nobel-Straße 10
40789 Monheim
GERMANY
Phone:
Fax:
Has been changed to:
Name:
Address:
UCB Biosciences GmbH
Alfred-Nobel-Straße 10
40789 Monheim
GERMANY
Phone:
Fax:
Change #2
Section List of Abbreviations
The following abbreviation has been deleted:
LFT
liver function test
The following abbreviations have been added:
ALP
alkaline phosphatase
PDILI
potential drug-induced liver injury
Change #3
Section 1 Summary, fourth paragraph and first paragraph after second 
bullet list
A Data Monitoring Committee (DMC) will systematically monitor and report on the progress, 
safety, and/or critical efficacy endpoints of the study. This includes evaluating the safety signals 
and benefit-risk balance for the study subjects in relationship to new data relevant for the 
efficacy and safety of the investigational medicinal product (IMP). The benefit-risk balance of 
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every subject entering the study will be reviewed by the DMC within 3 months after inclusion. 
Voting members of the DMC will include external physicians with experience in treating 
refractory epilepsy and a cardiologist. The DMC will make recommendations to the company 
about continuation of the study, which may include changes to study procedures, withdrawal or 
limiting inclusion of subjects with a negative benefit-risk balance, or termination of the clinical 
study.
Subjects being enrolled in the current study from EP0069 will be on UCB0942 400mg twice 
daily (bid) or a tapered UCB0942 dose of 200mg bid at the EV. They will continue this dose in 
the current study and there will be no tapering from the EP0069 dose before they receive the first 
dose in EP0073; however, throughout the Evaluation Period, the Investigator will be allowed to 
increase or decrease the dose of UCB0942 to optimize tolerability and seizure control for each 
subject. Increases or decreases to the dose of UCB0942 should be made in steps not exceeding 
200mg/day per week; an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is 
allowed. A faster decrease of the dose than 200mg/day per week is allowed when it is clinically 
appropriate in the Investigator's medical judgment. Daily UCB0942 doses during this study may 
be 100mg (50mg bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration. The dose 
of UCB0942 must always be administered as bid morning and evening doses, approximately 
12 hours apart. The first dose of the current study will be the dose on the evening of V2.
Has been changed to (changes bolded):
A Data Monitoring Committee (DMC) will systematically monitor and report on the progress, 
safety, and/or critical efficacy endpoints of the study. This includes evaluating the safety signals 
and benefit-risk balance for the study subjects in relationship to new data relevant for the 
efficacy and safety of the investigational medicinal product (IMP). The benefit-risk balance of 
every subject entering the study will be reviewed by the DMC within approximately 3 months 
after first dosing in EP0073. Voting members of the DMC will include external physicians with 
experience in treating refractory epilepsy and a cardiologist. The DMC will make 
recommendations to the company about continuation of the study, which may include changes to 
study procedures, withdrawal or limiting inclusion of subjects with a negative benefit-risk 
balance, or termination of the clinical study.
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP0069. They will continue this dose in the current study and there will be no 
tapering from the EP0069 dose before they receive the first dose in EP0073; however, 
throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
twice daily [bid]), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration. Exceptions 
may be allowed after consultation with the UCB Study Physician or PRA Medical Monitor.
The dose of UCB0942 must always be administered as bid morning and evening doses, 
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approximately 12 hours apart. The first dose of the current study will be the dose on the evening 
of V2.
Change #4
Section 2.3.2 Psychiatric adverse events
In the multiple ascending dose study, 1 healthy volunteer had a “delirious syndrome” with 
prominent psychotic symptoms, and in a subsequent Phase 1 study, 1 healthy volunteer had 
“mania-like symptoms.” Both of these AEs were classified as SAEs because the subjects 
required hospitalization. In both cases, the subjects fully recovered. After these psychiatric SAEs 
occurred, close psychiatric monitoring was implemented. Therefore, when 2 other healthy 
volunteers began to develop “hypomania” and “aggressive state,” respectively, the symptoms 
were discovered early, and discontinuation of UCB0942 possibly prevented the development of 
these symptoms into more severe psychiatric symptoms. Based on this, it appears that close 
psychiatric monitoring during the first 2 weeks of dosing, and tapering and discontinuation of the 
drug in subjects who start to develop psychiatric AEs, will reduce the risk that subjects develop 
more severe psychiatric AEs or psychiatric SAEs. 
In EP0069, daily psychiatric monitoring will be performed in all subjects for the first 2 weeks 
after dosing starts, and weekly thereafter. In the current OLE study, subjects will have a 
psychiatric (BPRS) and cognitive (MMSE) assessment at study visits every 3 months for years 1, 
2 and 3 and every 6 months for years 4 and 5. The CIWA-B will be performed at the LEPV (last 
visit prior to the Taper Period)/EDV, at the visit at the end of the Taper Period) and at SFU1 and 
SFU2 (1 week and 30 days after administration of the final dose of UCB0942, respectively). In 
addition, to further reduce the risk that participating subjects develop psychiatric AEs, subjects 
with a history of psychosis, schizophrenia, bipolar disorder, or severe unipolar depression will be 
excluded from this study. Lastly, based on the fact that titration has been shown to reduce the 
incidence of other AEs and increase the general tolerability of UCB0942, titration may also 
reduce the risk of psychiatric AEs.
Has been changed to (changes bolded):
In the course of UCB0942 development, 3 psychiatric SAEs (delirious syndrome, 
mania-like symptoms, and acute psychosis) have been reported in 2 healthy volunteers and 
1 patient with resistant epilepsy, respectively. The events were transient, acute, and 
required admission to psychiatric care and antipsychotics. The events in healthy subjects 
occurred early after initiation of UCB0942, which was done without titration. In 1 of the 
subjects symptoms worsened upon abrupt drug discontinuation. The psychotic effect in the 
epilepsy subject emerged after dramatic improvement in seizures control and 
electroencephalographic activity a few weeks after start of UCB0942, suggesting “forced 
normalization” (Loganathan et al, 2015; Clemens, 2005). Dose reduction of UCB0942 and 
neuroleptic treatment resulted in complete resolution of psychosis within days, as the 
treatment with UCB0942 continued. 
In EP0069, daily psychiatric monitoring is performed in all subjects for the first 2 weeks after 
dosing starts, and weekly thereafter. In the current OLE study, subjects will have a psychiatric 
(BPRS) and cognitive (MMSE) assessment at study visits every 3 months for years 1, 2 and 3 
and every 6 months for years 4 and 5. The CIWA-B will be performed at the LEPV (last visit 
prior to the Taper Period)/EDV, at the visit at the end of the Taper Period) and at SFU1 and 
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SFU2 (1 week and 30 days after administration of the final dose of UCB0942, respectively). In 
addition, to further reduce the risk that participating subjects develop psychiatric AEs, subjects 
with a history of psychosis, schizophrenia, bipolar disorder, or severe unipolar depression will be 
excluded from this study. Lastly, based on the fact that titration has been shown to reduce the 
incidence of other AEs and increase the general tolerability of UCB0942, titration may also 
reduce the risk of psychiatric AEs. 
Change #5
Section 5.1 Study description, third paragraph and first paragraph after 
second bullet list
A DMC will systematically monitor and report on the progress, safety, and/or critical efficacy 
endpoints of the study. This includes evaluating the safety signals and benefit-risk balance for 
the study subjects in relationship to new data relevant for the efficacy and safety of the IMP. The 
benefit-risk balance of every subject entering the study will be reviewed by the DMC within 3 
months after inclusion. Voting members of the DMC will include external physicians with 
experience in treating refractory epilepsy and a cardiologist. The DMC will make 
recommendations to the company about continuation of the study, which may include changes to 
study procedures, withdrawal or limiting inclusion of subjects with a negative benefit-risk 
balance, or termination of the clinical study.
Subjects being enrolled in the current study from EP0069 will be on UCB0942 400mg bid or a 
tapered UCB0942 dose of 200mg bid at the EV. They will continue this dose in the current study 
and there will be no tapering from the EP0069 dose before they receive the first dose in EP0073; 
however, throughout the Evaluation Period, the Investigator will be allowed to increase or 
decrease the dose of UCB0942 to optimize tolerability and seizure control for each subject. 
Increases or decreases to the dose of UCB0942 should be made in steps not exceeding 
200mg/day per week; an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is
allowed. A faster decrease of the dose than 200mg/day per week is allowed when it is clinically 
appropriate in the Investigator's medical judgment. Daily UCB0942 doses during this study may 
be 100mg (50mg bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration. The dose 
of UCB0942 must always be administered as bid morning and evening doses, approximately 
12 hours apart. The first dose of the current study will be the dose on the evening of V2.
Has been changed to (changes bolded):
A DMC will systematically monitor and report on the progress, safety, and/or critical efficacy 
endpoints of the study. This includes evaluating the safety signals and benefit-risk balance for 
the study subjects in relationship to new data relevant for the efficacy and safety of the IMP. The 
benefit-risk balance of every subject entering the study will be reviewed by the DMC within 
approximately 3 months after first dosing in EP0073. Voting members of the DMC will 
include external physicians with experience in treating refractory epilepsy and a cardiologist. 
The DMC will make recommendations to the company about continuation of the study, which 
may include changes to study procedures, withdrawal or limiting inclusion of subjects with a 
negative benefit-risk balance, or termination of the clinical study.
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP0069. They will continue this dose in the current study and there will be no 
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tapering from the EP0069 dose before they receive the first dose in EP0073; however, 
throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg (400mg bid); 
intermediate doses will not be allowed except for tapering and titration. Exceptions may be 
allowed after consultation with the UCB Study Physician or PRA Medical Monitor. The 
dose of UCB0942 must always be administered as bid morning and evening doses, 
approximately 12 hours apart. The first dose of the current study will be the dose on the evening 
of V2.
Change #6
Section 5.1.2 Planned number of subjects and sites
It is estimated that approximately 30 subjects who completed EP0069 will be included in 
multiple sites in Europe.
Has been changed to (change bolded):
It is estimated that approximately 40 subjects who completed EP0069 will be included in 
multiple sites in Europe.
Change #7
Section 5.3 Schedule of study assessments, Table 5-2, footnote (b)
b From EP0069 study. Update if necessary.
Has been changed to:
b Demographic and general medical/procedure history data will be obtained from EP0069 and 
updated if necessary. Information regarding surgical evaluation, working status, caregiver 
support, and supervision should be collected within 30 days after Protocol Amendment 2 is 
approved.
Change #8
Section 5.4 Rationale for study design and selection of dose, second and 
last paragraphs
Subjects being enrolled in the current study from EP0069 will be on UCB0942 400mg bid or a 
tapered UCB0942 dose of 200mg bid at the EV. The highest UCB0942 dose of 400mg bid used 
in this study has been chosen because it is the maximum tolerated dose in Phase 1 studies. 
Throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
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Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg (400mg bid); 
intermediate doses will not be allowed except for tapering and titration.
Has been changed to (changes bolded):
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP006. In EP0073 doses can range from 50mg bid to 400mg bid. The highest 
UCB0942 dose of 400mg bid used in this study has been chosen because it is the maximum 
tolerated dose in Phase 1 studies. 
Throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg (400mg bid); 
intermediate doses will not be allowed except for tapering and titration unless agreed by the 
UCB Study Physician or PRA Medical Monitor.
Change #9
Section 6.1 Inclusion criteria, Inclusion Criterion #8 (bolded text has been 
deleted)
Male subject confirms that, during the study period and for a period of 3 months after the final 
dose, when having sexual intercourse with a woman of childbearing potential, he will use a 
barrier contraceptive (eg, condom) AND that the respective partner will use an additional 
contraceptive method.
Has been changed to:
Male subject confirms that, during the study period and for a period of 3 months after the final 
dose, when having sexual intercourse with a woman of childbearing potential, he will use a 
barrier contraceptive (eg, condom).
Change #10
Section 6.2 Exclusion criteria
Added the following Exclusion Criterion #12:
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 
(≥1.5xULN total bilirubin if known Gilbert’s syndrome) at the EV (V2) of EP0073 (V15 of 
EP0069). 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 enrolled 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 in the electronic Case Report form (eCRF).
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If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at screening (ie, 
the value is >ULN but ≤2xULN at the EV [V2] of EP0073), 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.
Change #11
Section 6.3 Withdrawal criteria, third paragraph
Investigators should contact the UCB Study Physician, whenever possible, to discuss the 
withdrawal of a subject in advance.
Has been changed to (change bolded):
Investigators should contact the UCB Study Physician or PRA Medical Monitor, whenever 
possible, to discuss the withdrawal of a subject in advance.
Change #12
Section 6.3 Withdrawal criteria, Withdrawal Criterion #2
In the case of liver function test (LFT) results of transaminases (aspartate aminotransferase 
[AST] and/or alanine aminotransferase [ALT]) ≥3x upper limit of normal (ULN) to <5x ULN 
and total bilirubin ≥2x ULN or transaminases (AST and/or ALT) ≥5x ULN, UCB0942 must be 
immediately discontinued and the subject withdrawn from the study. The LFTs will be repeated 
as soon as possible, and in no case more than 1 week later.
Has been deleted
Change #13
Section 6.3 Withdrawal criteria, previous Withdrawal Criterion #3 (currently 
#2), last 2 bullets

ALT ≥2x ULN

AST ≥2x ULN
Have been deleted
Change #14
Section 6.3 Withdrawal criteria, previous Withdrawal Criterion #8 (currently 
#7), first and last bullets

Carbamazepine, phenytoin, phenobarbital, primidone, or other strong CYP3A4 inducers

Non-AED CYP3A4 inducers/inhibitors (ie, prescription drugs, nonprescription drugs, 
dietary [eg, grapefruit or passion fruit], or herbal products)
Have been changed to (changes bolded):

Carbamazepine, phenytoin, phenobarbital, primidone, or other AEDs that are strong 
CYP3A4 inducers

Strong non-AED CYP3A4 inducers/inhibitors (ie, prescription drugs, nonprescription 
drugs, dietary [eg, grapefruit or passion fruit], or herbal products)
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(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/D
rugInteractionsLabeling/ucm093664.htm)
Change #15
Section 6.3 Withdrawal criteria, previous Withdrawal Criterion #17
(currently #16), paragraph
Subject develops psychiatric/mood/behavioral signs or disturbances (see examples in list below) 
that are clinically concerning or that worsen over time. Tapering and discontinuation of 
UCB0942 should be performed in such subjects and they should be referred to a mental health 
professional.
Has been changed to (changes bolded):
For subjects developing psychiatric/mood/behavioral signs or disturbances (see examples in list 
below) that are clinically concerning or that worsen over time, the study drug dose should be 
gradually reduced and, if symptoms persist, withdrawal from study should be 
recommended. Subjects should be referred to a mental health professional, and continuation 
of the study treatment should only be allowed with the approval and under close oversight 
of the mental health specialist, and upon confirmation of the positive benefit-risk by the 
Investigator.
Change #16
Section 6.3 Withdrawal criteria
Added Section 6.3.1 Potential drug-induced liver injury IMP discontinuation 
criteria: 
Subjects with potential drug-induced liver injury (PDILI) must be assessed to determine if IMP 
must be discontinued. In addition, all concomitant medications and herbal supplements that are 
not medically necessary should also be discontinued. 
The PDILI criteria below require immediate and permanent discontinuation of IMP: 

Subjects with either of the following:

ALT or AST ≥5xULN

ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN 
The PDILI criterion below requires immediate discontinuation of IMP:

Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%).
If a nondrug-related cause for the symptoms can be confirmed, these subjects may resume IMP 
administration after discussion with the responsible UCB physician, but only when the 
requirements for rechallenge with IMP as provided in Section 11.6.1.2.1 are followed.
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
Investigator. 
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
Subjects with ALT or AST ≥3xULN (and ≥2x baseline) and <5xULN, total bilirubin 
<2xULN, and no eosinophilia (ie, ≤5%), with no fever, rash, or symptoms of hepatitis (eg, 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness).
Evaluation of PDILI must be initiated as described in Section 11.6.1. If subjects are unable to 
comply with the applicable monitoring schedule, IMP must be discontinued immediately.
Investigators should attempt to obtain information on subjects in the case of IMP discontinuation 
to complete the final evaluation. Subjects with PDILI should not be withdrawn from the study 
until investigation and monitoring are complete. All results of these evaluations and 
observations, as well as the reason(s) for IMP discontinuation and subject withdrawal (if 
applicable), must be recorded in the source documents. The eCRF must document the primary 
reason for IMP discontinuation.
Change #17
Section 7.1 Description of investigational medicinal product(s), Table 7-1, 
Manufacturer
The following text has been added:
Catalent Micron Technologies
Crossways Boulevard
Crossways Dartford, Kent
DA2 6QY United Kingdom
Change #18
Section 7.2 Treatments to be administered, first and third paragraphs
Subjects being enrolled in the current study from EP0069 will be on UCB0942 400mg bid or a 
tapered UCB0942 dose of 200mg bid at the EV. They will continue this dose in the current study 
and there will be no tapering from the EP0069 dose before they receive the first dose in EP0073; 
however, throughout the Evaluation Period, the Investigator will be allowed to increase or 
decrease the dose of UCB0942 to optimize tolerability and seizure control for each subject. 
Increases or decreases to the dose of UCB0942 should be made in steps not exceeding 
200mg/day per week; an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is 
allowed. A faster decrease of the dose than 200mg/day per week is allowed when it is clinically 
appropriate in the Investigator's medical judgment. Daily UCB0942 doses during this study may 
be 100mg (50mg bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration. The dose 
of UCB0942 must always be administered as bid morning and evening doses, approximately 
12 hours apart. The first dose of the current study will be the dose on the evening of V2.
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. The UCB Study Physician must be consulted prior to 
initiation of concomitant AED withdrawal. New concomitant AEDs may be introduced to 
optimize tolerability and seizure reduction, if the concomitant medication has been approved for 
focal seizures by the health authority of the subject’s country of residence, taking the drug to 
drug interactions profile of UCB0942 into account. New AEDs (with the exception of AEDs 
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listed in the prohibited medication section, Section 7.8.2) should be added only when the subject 
has not optimally or adequately responded to a maximum tolerated dose of UCB0942.
Have been changed to (changes bolded):
Subjects being enrolled in the current study from EP0069 will continue their dose in the current 
study and there will be no tapering from the EP0069 dose before they receive the first dose in 
EP0073; however, throughout the Evaluation Period, the Investigator will be allowed to increase 
or decrease the dose of UCB0942 to optimize tolerability and seizure control for each subject. 
Increases or decreases to the dose of UCB0942 should be made in steps not exceeding 
200mg/day per week; an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is 
allowed. A faster decrease of the dose than 200mg/day per week is allowed when it is clinically 
appropriate in the Investigator's medical judgment. Daily UCB0942 doses during this study may 
be 100mg (50mg bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration unless 
agreed by the UCB Study Physician or PRA Medical Monitor. The dose of UCB0942 must 
always be administered as bid morning and evening doses, approximately 12 hours apart. The 
first dose of the current study will be the dose on the evening of V2. 
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. The UCB Study Physician or PRA Medical Monitor
must be consulted prior to initiation of concomitant AED withdrawal. New concomitant AEDs 
may be introduced to optimize tolerability and seizure reduction, if the concomitant medication 
has been approved for focal seizures by the health authority of the subject’s country of residence, 
taking the drug to drug interactions profile of UCB0942 into account. New AEDs (with the 
exception of AEDs listed in the prohibited medication section, Section 7.8.2) should be added 
only when the subject has not optimally or adequately responded to a maximum tolerated dose of 
UCB0942.
Change #19
Section 7.8.1 Permitted concomitant treatments (medications and 
therapies), first and last bullets (bolded text has been deleted)

All subjects will enter EP0073 using their current AED regimen. Concomitant AEDs and 
AED dose(s), or VNS settings may be adjusted throughout EP0073 as per the Investigator's 
clinical judgment based on tolerability and seizure control for each individual subject. 
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. New concomitant AEDs may be introduced to 
optimize tolerability and seizure reduction. Changes in AEDs should be discussed with the 
UCB Study Physician on an individual and case-by-case basis.

Other medication, not mentioned as prohibited, that does not induce CYP3A4 and is 
approved by the UCB Study Physician.
Have been changed to (change bolded):

All subjects will enter EP0073 using their current AED regimen. Concomitant AEDs and 
AED dose(s), or VNS settings may be adjusted throughout EP0073 as per the Investigator’s 
clinical judgment based on tolerability and seizure control for each individual subject. 
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Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. New concomitant AEDs may be introduced to 
optimize tolerability and seizure reduction. Changes in AEDs should be discussed with the 
UCB Study Physician or PRA Medical Monitor on an individual and case-by-case basis.

Other medication, not mentioned as prohibited.
Change #20
Section 7.8.2 Prohibited concomitant treatments (medications and 
therapies), first, second, and last bullets

Carbamazepine, phenytoin, phenobarbital, primidone, or other strong CYP3A4 inducers

Benzodiazepines taken >3 times per week

Non-AED CYP3A4 inducers/inhibitors (ie, prescription drugs, nonprescription drugs, dietary 
[eg, grapefruit or passion fruit], or herbal products)
Have been changed to (changes bolded):

Carbamazepine, phenytoin, phenobarbital, primidone, or other AEDs that are strong 
CYP3A4 inducers

Benzodiazepines taken >3 times per week (ie, >3 doses within 7 days)

Strong non-AED CYP3A4 inducers/inhibitors (ie, prescription drugs, nonprescription drugs, 
dietary [eg, grapefruit or passion fruit], or herbal products)
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Drug
InteractionsLabeling/ucm093664.htm)
Change #21
Section 7.9 Blinding
This is an OLE study so no blinding is required. A DMC (see Section 13.8) will review blinded 
data up until final database lock from EP0069 and data from the OLE EP0073 studies in order 
for the DMC to provide an ongoing evaluation of the safety signals and the benefit-risk balance 
for the study subjects.
Has been changed to (changes bolded):
This is an OLE study so no blinding is required. A DMC (see Section 13.8) will review blinded 
data up until final unblinding from EP0069 and data from the OLE EP0073 studies to provide 
an ongoing evaluation of the safety signals and the benefit-risk balance for the study subjects.
Change #22
Section 8.2.1 Entry Visit, paragraph and first 2 bullets
The EV, V2, is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of 
EP0069. During the EV the following assessments will be performed:

Review demographic, medical, medication, and procedural data from EP0069; update where 
necessary.
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
Concomitant AEDs and non-AEDs; ongoing medications (AEDs and non-AEDs) at the time 
of subject completion of EP0069  will be obtained from the database for EP0069 and should 
not be recorded in the eCRF for EP0073  unless there is a change regarding the 
administration of the medication. In this event, the medication should be recorded in the 
eCRF for EP0073 with the start date corresponding to the date of change in administration.
Have been changed to (changes bolded):
The EV, V2, is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of 
EP0069. Data collected at V15 in EP0069 must also be recorded at V2 in the EP0073 eCRF.
During the EV the following assessments will be performed:

Review demographic, medical, medication, and procedural data from EP0069 and update 
where necessary; collect information regarding surgical evaluation, working status, 
caregiver support, and supervision within 30 days after Protocol Amendment 2 is 
approved.

Concomitant AEDs and non-AEDs; any ongoing concomitant medications from EP0069 
must also be recorded on the EP0073 eCRF. Details are provided in the eCRF 
Completion Guidelines.
Change #23
Section 11.1.8 Safety signal detection, third paragraph
Any findings from this review will be brought to the attention of the DMC, that will 
systematically monitor and report on the progress, safety, and/or critical efficacy endpoints of the 
study by convening to review the ongoing program safety and efficacy data. This includes 
evaluating the safety signals and benefit-risk balance for the study subjects in relationship with 
new data relevant for IMP efficacy and safety. The benefit-risk balance of every subject entering 
the study will be reviewed by the DMC within 3 months after inclusion. Voting members of the 
DMC will include external physicians with experience in treating refractory epilepsy and a 
cardiologist. The DMC will make recommendations to the company about continuation of the 
study, which may include changes to study procedures, withdrawal or limiting inclusion of 
subjects with a negative benefit risk balance, or termination of the clinical study. The precise 
membership, scope, and responsibilities of the DMC are described in the DMC Charter.
Has been changed to (changes bold):
Any findings from this review will be brought to the attention of the DMC, that will 
systematically monitor and report on the progress, safety, and/or critical efficacy endpoints of the 
study by convening to review the ongoing program safety and efficacy data. This includes 
evaluating the safety signals and benefit-risk balance for the study subjects in relationship with 
new data relevant for IMP efficacy and safety. The benefit-risk balance of every subject entering 
the study will be reviewed by the DMC within approximately 3 months after first dosing in 
EP0073. Voting members of the DMC will include external physicians with experience in 
treating refractory epilepsy and a cardiologist. The DMC will make recommendations to the 
company about continuation of the study, which may include changes to study procedures, 
withdrawal or limiting inclusion of subjects with a negative benefit-risk balance, or termination 
of the clinical study. The precise membership, scope, and responsibilities of the DMC are 
described in the DMC Charter.
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Change #24
Section 11.3 Adverse events of special interest, second paragraph
There are no AEs of special interest to be reported for UCB0942.
Has been changed to:
Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total bilirubin in 
the absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, 
must ALWAYS be reported to UCB as an AE of special interest (ie, without waiting for any 
additional etiologic investigations to have been concluded). Follow-up information should then 
be reported if an alternative etiology is identified during investigation and monitoring of the 
subject.
Change #25
Section 11.6 Laboratory assessments
Added Section 11.6.1 Evaluation of PDILI:
11.6.1 Evaluation of PDILI
The PDILI IMP discontinuation criteria for this study are provided in Section 6.3.1, with the 
accompanying required follow-up investigation and monitoring detailed below. All PDILI events 
must be reported as an AE and reported to the study site and Sponsor within 24 hours of learning 
of their occurrence. Any PDILI event that meets the criterion for potential Hy’s Law must be 
reported as an AE of special interest (see Section 11.3), and, if applicable, also reported as an 
SAE (see Section 11.1.1). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 11‒3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 11.6.1.1). The local 
hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. Additional investigation and monitoring may be required and adapted based 
on the diagnosis after the cause of the liver injury/abnormality is confirmed (details in 
Section 11.6.1.4). 
The results of all monitoring, including laboratory testing and other testing, should be made 
available to the study site and Sponsor.
All initial tests resulting in abnormal hepatic laboratory values need to be repeated, but 
appropriate medical action must not be delayed waiting for the repeat result.
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 
2 laboratory tests are significantly different. Data from the local and central laboratory are to be 
recorded on the applicable eCRF pages.
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the Investigator should also 
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consider dose reduction for medically necessary concomitant medication and consider changing 
any medically required concomitant medication known to be hepatotoxic to a suitable 
alternative.
When IMP is stopped due to PDILI (as described in Section 6.3.1), IMP must be permanently 
discontinued unless a subsequent alternative diagnosis fully explains the hepatic findings. If a 
subsequent alternative diagnosis fully explains the hepatic findings, and the requirements 
provided in Section 11.6.1.2.1 are met, rechallenge with IMP may be appropriate. 
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
The table below summarizes the approach to investigate PDILI.
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Table 11-3: Required investigations and follow up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consult.c
Medical Monitor 
must be notified 
within 24 hours 
(eg, by laboratory 
alert) and subject 
discussed with 
Medical Monitor 
ASAP.
Immediate, 
permanent IMP 
discontinuation.
Essential: Must 
have repeat liver 
chemistry values 
and additional 
testing completed 
ASAP (see 
Section 11.6.1.3); 
recommended to 
occur at the site 
with HCP.
Monitoring of liver chemistry 
values at least twice per week 
until values normalize, stabilize, 
or return to within baseline 
values.d
≥8xULN
NA
NA
≥3xULN
NA
Yes
Immediate, 
temporary or 
permanent, IMP 
discontinuation.
≥3xULN 
(and ≥2x 
baseline) 
and 
<5xULN
<2xULN
No
Discussion with 
Medical Monitor 
required if the 
criterion that allows 
for IMP continuation 
is met.
Further investigation 
– immediate IMP 
discontinuation not 
required (see 
Section 11.6.1.2).
Not required 
unless otherwise 
medically 
indicated (at 
discretion of the 
Investigator).
≥5xULN 
(and ≥2x 
baseline) 
<2xULN
No
Discussion with 
Medical Monitor 
required.
Immediate, 
permanent IMP 
discontinuation.
Essential: Every 
attempt must be 
made to have 
repeat liver 
chemistry values 
and additional 
testing completed 
within 48 hours 
at the site with 
HCP (see 
Section 11.6.1.3).
Monitoring of liver chemistry 
values at least twice per week 
until values normalize, stabilize, 
or return to within baseline 
values.d
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Table 11-3: Required investigations and follow up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug-induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause).
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor.
c Details provided in Section 11.6.1.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of 
potential hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
d Unless an alternative monitoring schedule is agreed by the Investigator and UCB responsible physician. Determination of stabilization is at the discretion of 
the Investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
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11.6.1.1
Consultation with the Medical Monitor and local hepatologist
Potential drug-induced liver injury events require notification of the Medical Monitor within 
24 hours (eg, by laboratory alert), and the subject must be discussed with the Medical Monitor as 
soon as possible. If required, the subject must also be discussed with the local hepatologist. The 
local hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. If determined necessary, this discussion should be followed by a full 
hepatology assessment (see Section11.6.1.3) and SAE report (if applicable).
11.6.1.2
Immediate action: determination of IMP discontinuation
All PDILI events require immediate action, testing, and monitoring. 
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 11‒3 for details).
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. The Investigator should also consider dose 
reduction for medically necessary concomitant medication and consider changing any medically 
required concomitant medication known to be hepatotoxic to a suitable alternative.
11.6.1.2.1
IMP restart/rechallenge (if applicable)
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
Subjects who are immediately discontinued from IMP due to having met certain criteria for 
PDILI (as described in Section 6.3.1 and Table 11‒3), but for whom an alternative diagnosis is 
confirmed, can rarely restart IMP. Rechallenge with IMP can occur only if ALL of the following 
requirements are met:

The results of additional testing and monitoring described in Section 11.6.1.3 and 
Section 11.6.1.4 confirm a nondrug-related cause for the abnormal hepatic laboratory 
parameters and any associated symptoms (ie, a subsequent alternative diagnosis fully 
explains the hepatic findings). 

No alternative treatment options are available to the subject.

The subject has shown clear therapeutic benefit from the IMP.

Subject’s ALT or AST elevations do not exceed ≥3xULN.

Subject’s total bilirubin is <1.5xULN.

Subject has no signs or symptoms of hypersensitivity. 

The rechallenge is approved by the UCB responsible physician and a hepatologist. The 
hepatologist must be external to UCB. It is recommended that the hepatologist be a local 
hepatology expert or the hepatologist treating the subject.

Subject agrees to the Investigator-recommended monitoring plan.
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11.6.1.3
Testing: identification/exclusion of alternative etiology
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that they may have been caused by the IMP are detailed in 
Table 11‒4 (laboratory measurements) and Table 11‒5 (additional information). Results of the 
laboratory measurements and information collected are to be submitted to the Sponsor on the 
corresponding eCRF. If the medical history of the subject indicates a requirement for other 
assessments not included below, these additional assessments should be completed and 
submitted, as applicable.
All blood samples should be stored, if possible. If tests are done locally for more rapid results, a 
concurrent sample must also be sent to the central laboratory.
The following measurements are to be assessed:
Table 11-4: PDILI laboratory measurements
Virology-
related
Hepatitis A IgM antibody
HBsAg
Hepatitis E IgM antibody
HBcAb-IgM
Hepatitis C RNA
Cytomegalovirus IgM antibody
Epstein-Barr viral capsid antigen IgM antibody (if unavailable, obtain heterophile 
antibody or monospot testing)
Immunology
Anti-nuclear antibody (qualitative and quantitative)
Anti-smooth muscle antibody (qualitative and quantitative)
Type 1 anti-liver kidney microsomal antibodies (qualitative and quantitative)
Hematology
Eosinophil count
Urinalysis
Toxicology screen
Chemistry
Amylase
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % direct bilirubin
Serum CPK and LDH to evaluate possible muscle injury causing transaminase elevation
Additional
Prothrombin time/INRa
Serum pregnancy test
PK sample
ALT=alanine aminotransferase; CPK=creatine phosphokinase; HBcAb-IgM=hepatitis B core antibody-IgM; 
HBsAg=hepatitis B surface antigen; IgM=immunoglobulin M; INR=international normalized ratio; LDH=lactate 
dehydrogenase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; RNA=ribonucleic acid; 
ULN=upper limit of normal
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Table 11-4: PDILI laboratory measurements
a Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
The following additional information is to be collected: 
Table 11-5: PDILI information to be collected
New or updated information
Concomitant prescription and over-the-counter medications (eg, acetaminophen, herbal remedies, 
vitamins); dosages and dates should be included.
Pertinent medical history, including the following:

History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty 
liver disease”)

Adverse reactions to drugs

Allergies

Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 antitrypsin 
deficiency)

Recent travel 

Progression of malignancy involving the liver (Note: Metastatic disease to the liver, by itself, 
should not be used as an explanation for significant AST and/or ALT elevations.)
The appearance or worsening of clinical symptoms of hepatitis or hypersensitivity (eg, fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, decreased appetite, abdominal pain, jaundice, fever, or 
rash)
Recent clinically significant hypotension or hypoxemia with compromised cardiopulmonary function
Alcohol and illicit drug use
Results of liver imaging or liver biopsy, if done
Results of any specialist or hepatology consult, if done
Any postmortem/pathology reports
ALT=alanine aminotransferase; AST=aspartate aminotransferase; PDILI=potential drug-induced liver injury
11.6.1.4
Follow-up evaluation
Potential drug-induced liver injury events require follow-up and monitoring as described in 
Table 11‒3. Monitoring should continue until liver chemistry values normalize, stabilize, or 
return to baseline. Determination of stabilization is at the discretion of the Investigator in 
consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
Change #26
Section 13.8 Planned interim analysis and data monitoring, first paragraph
A DMC will systematically monitor and report (at least quarterly up to the time point when the 
last patient entering EP0073 reaches 1 year in the study, and less frequent thereafter) on the 
progress, safety, and/or critical efficacy endpoints of this study by convening to review the 
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ongoing program safety and efficacy data. This includes evaluating the safety signals and 
benefit-risk balance for the study subjects in relationship to new data relevant for IMP efficacy 
and safety. The benefit-risk balance of every subject entering the study will be reviewed by the 
DMC within 3 months after inclusion. Blinded data until database lock from EP0069 and data 
from the OLE EP0073 studies will be reviewed in order for the DMC to provide an ongoing risk 
benefit evaluation with particular reference to the occurrence of psychiatric and 
cardiological/cardiovascular AEs, seizure control, and any new identified safety signals.  
Has been changed to (changes bolded):
A DMC will systematically monitor and report (at least quarterly up to the time point when the 
last patient entering EP0073 reaches 1 year in the study, and less frequent thereafter) on the 
progress, safety, and/or critical efficacy endpoints of this study by convening to review the 
ongoing program safety and efficacy data. This includes evaluating the safety signals and 
benefit-risk balance for the study subjects in relationship to new data relevant for IMP efficacy 
and safety. The benefit-risk balance of every subject entering the study will be reviewed by the 
DMC approximately 3 months after first dosing in EP0073. Blinded data until database lock 
from EP0069 and data from the OLE EP0073 studies will be reviewed in order for the DMC to 
provide an ongoing risk benefit evaluation with particular reference to the occurrence of 
psychiatric and cardiological/cardiovascular AEs, seizure control, and any new identified safety 
signals.
Change #27
Section 13.9 Determination of sample size
For this OLE study, no sample size calculation is needed. The sample size will depend upon 
recruitment into and completion of the previous study. It is estimated that about 30 subjects 
(75%) from EP0069 will enter this EP0073 study.
Has been changed to (change bolded):
For this OLE study, no sample size calculation is needed. The sample size will depend upon 
recruitment into and completion of the previous study. It is estimated that about 40 subjects 
from EP0069 will enter this EP0073 study.
Change #28 Section 16 References
The following 2 references have been added:
Clemens B. Forced normalisation precipitated by lamotrigine. Seizure. 2005; 14:485-9.
Loganathan MA, Enja M, Lippmann S. FORCED NORMALIZATION: Epilepsy and Psychosis 
Interaction. Innov Clin Neurosci. 2015; 12(5-6): 38–41. 
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17.3
Protocol Amendment 3
Rationale for the amendment
The primary purpose of this substantial amendment is to change the frequency for the 
echocardiogram assessments after the YEAR 2. Of note, no subjects have reached this milestone 
at the time of this protocol amendment, and therefore no impact on the safety analysis is 
expected. The changes made to a footnote in the Schedule of Events and text in the Study 
Procedures by Visit section are consistent with the original intention as stated in Section 2.3.1 in 
the original protocol and subsequent amendments: “subjects will have an echocardiogram at 
Visit 2 and every 3 months for the first year and second year of treatment, and every 6 months in 
subsequent years to ensure early detection of any valvular or pericardial changes that may 
occur.” In addition, following the annual revision of the Investigator’s Brochure 2017 for 
padsevonil, the following prohibited concomitant medications have been added in this protocol: 
strong CYP2C19 inhibitors, strong CYP2C19 inducers, and CYP2C19 sensitive substrates. It is 
to be specified that the because recruitment has been completed for EP0073, subjects who were 
already taking these medications prior to Amendment 3, may continue to do so, but close 
monitoring should be implemented.
The other main changes in this amendment are as follows:

Clarified that a subject with a benefit-risk ratio of 0 to 4 (on a scale from 0 to 10) must be 
withdrawn from the study.

Removed the UCB Study Physician as one of the contact points for the sites (PRA Medical 
Monitor remains in place).   

Added adverse events of special interest to the list of AEs requiring immediate reporting.

Updated text to allow alternate assessments if echocardiograms are not usable during the 
study.

Deleted text that states subjects with a positive benefit-risk ratio (6 to 10) are allowed to 
continue in the study, since subjects with a neutral benefit-risk ratio (5) are also allowed to 
continue.

Defined the Pharmacokinetic Per-Protocol Set that will be used for the PK analysis. This is to 
fulfill an omission in the previous version of the protocols. No change in the SAP has 
occurred. 

Simplified the sections related to the IMP. 
Modifications and changes
Specific changes
Change #1
List of Abbreviations, the following abbreviations have been added:  
CMR
cardiac magnetic resonance
DDI
drug-drug interaction(s)
FAS
Full Analysis Set
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Change #2
STUDY CONTACT INFORMATION
Clinical Trial Biostatistician
Name:
Address:
UCB Biosciences Inc.
P.O. Box 110167
Research Triangle Park, NC 27709
USA
Phone:
Fax:
Has been changed to: 
Clinical Trial Biostatistician
Name:
Address:
UCB Pharma Ltd.
280 Bath Road
Berkshire SL 13WE Slough
UK
Phone:
Change #3
Section 1 Summary, fourth paragraph, first bullet, second bullet (first 
paragraph only), and first paragraph after the second bullet list
A Data Monitoring Committee (DMC) will systematically monitor and report on the progress, 
safety, and/or critical efficacy endpoints of the study. This includes evaluating the safety signals 
and benefit-risk balance for the study subjects in relationship to new data relevant for the 
efficacy and safety of the investigational medicinal product (IMP). The benefit-risk balance of 
every subject entering the study will be reviewed by the DMC within approximately 3 months 
after first dosing in EP0073. Voting members of the DMC will include external physicians with 
experience in treating refractory epilepsy and a cardiologist. The DMC will make 
recommendations to the company about continuation of the study, which may include changes to 
study procedures, withdrawal or limited inclusion of subjects with a negative benefit-risk 
balance, or termination of the clinical study.
The study will consist of:

A 2-week Screening Period from Visit 13 (V13) to V15 (Days OP43 to OP57) of the 8-week 
Outpatient Maintenance Period of the EP0069 study. The Screening Visit will be on V13 of 
EP0069 and will be V1 of the current OLE study. At this visit, informed consent will be 
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signed and inclusion and exclusion criteria (from the current OLE study) will be checked. 
The verbatim of the attained benefits of treatment with UCB0942, including seizure control, 
health and well-being, and social functioning, declared by a subject/caregiver will be 
captured as narratives and filled in by the Investigator or site personnel. During the Screening 
Period, the Investigator will also provide a statement and a brief justification of positive 
benefit-risk balance for each subject’s participation in EP0073 and long-term treatment with 
UCB0942. These narratives of benefit by the subject/caregiver and the benefit-risk statement 
and the justification by the Investigator will be maintained as source documents and will be 
reviewed by the DMC. 

An Evaluation Period of up to approximately 5 years, which will start with V2, the Entry 
Visit (EV), which is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance 
Period of EP0069. Eligible subjects will enter EP0073 before the planned dose tapering in 
EP0069. Subjects will be issued and return seizure diaries during each visit. Subjects must be 
educated to record all types of seizures that occur, any illness or injury, and all study 
medication intake in their seizure diary and be educated to complete their diary entries after 
each seizure or at least once a day. Throughout the study, the Investigator also will be 
requested to periodically re-assess and re-confirm that the benefit-risk ratio for the subject of 
the long-term treatment with the IMP, considering the knowledge of the IMP’s efficacy and 
safety profile and alternative treatment options, remains positive. Narratives of benefit by the 
subject/caregiver and the benefit-risk statement and the justification by the Investigator will 
be captured in a dedicated form at the scheduled time points presented in Table 5-2.
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP0069. They will continue this dose in the current study and there will be no 
tapering from the EP0069 dose before they receive the first dose in EP0073; however, 
throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
twice daily [bid]), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration. Exceptions 
may be allowed after consultation with the UCB Study Physician or PRA Medical Monitor. The 
dose of UCB0942 must always be administered as bid morning and evening doses, 
approximately 12 hours apart. The first dose of the current study will be the dose on the evening 
of V2.
Has been changed to (change bolded):
A Data Monitoring Committee (DMC) will systematically monitor and report on the progress, 
safety, and/or critical efficacy endpoints of the study. This includes evaluating the safety signals 
and benefit-risk balance for the study subjects in relationship to new data relevant for the 
efficacy and safety of the investigational medicinal product (IMP). The benefit-risk balance of 
every subject entering the study will be reviewed by the DMC within approximately 3 months 
after first dosing in EP0073. Voting members of the DMC will include external physicians with 
experience in treating refractory epilepsy and a cardiologist. The DMC will make 
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recommendations to the company about continuation of the study, which may include changes to 
study procedures, or termination of the clinical study.
The study will consist of:

A 2-week Screening Period from Visit 13 (V13) to V15 (Days OP43 to OP57) of the 8-week 
Outpatient Maintenance Period of the EP0069 study. The Screening Visit will be on V13 of 
EP0069 and will be V1 of the current OLE study. At this visit, informed consent will be 
signed and inclusion and exclusion criteria (from the current OLE study) will be checked. 
The verbatim of the attained benefits of treatment with UCB0942, including seizure control, 
health and well-being, and social functioning, declared by a subject/caregiver will be 
captured as narratives and filled in by the Investigator or site personnel. During the Screening 
Period, the Investigator will also provide a statement and a brief justification of the 
benefit-risk balance for each subject’s participation in EP0073 and long-term treatment with 
UCB0942. These narratives of benefit by the subject/caregiver and the benefit-risk statement 
and the justification by the Investigator will be maintained as source documents and will be 
reviewed by the DMC. 

An Evaluation Period of up to approximately 5 years, which will start with V2, the Entry 
Visit (EV), which is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance 
Period of EP0069. Eligible subjects will enter EP0073 before the planned dose tapering in 
EP0069. Subjects will be issued and return seizure diaries during each visit. Subjects must be 
educated to record all types of seizures that occur, any illness or injury, and all study 
medication intake in their seizure diary and be educated to complete their diary entries after 
each seizure or at least once a day. Throughout the study, the Investigator also will be 
requested to periodically re-assess and re-confirm that the benefit-risk ratio for the subject on
long-term treatment with the IMP, considering the knowledge of the IMP’s efficacy and 
safety profile and alternative treatment options, justifies continuation in the study.
Narratives of benefit by the subject/caregiver and the benefit-risk statement and the 
justification by the Investigator will be captured in a dedicated form at the scheduled time 
points presented in Table 5-2.
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP0069. They will continue this dose in the current study and there will be no 
tapering from the EP0069 dose before they receive the first dose in EP0073; however, 
throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
twice daily [bid]), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration. Exceptions 
may be allowed after consultation with the PRA Medical Monitor. The dose of UCB0942 must 
always be administered as bid morning and evening doses, approximately 12 hours apart. The 
first dose of the current study will be the dose on the evening of V2.
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Change #4
Section 2.3 Risks and mitigation strategy
The two important identified risks based on the human pharmacology studies to date include 
drug-drug interactions with potent cytochrome P450 (CYP) 3A4 enzyme inducers and the risk of 
developing psychiatric symptoms. The potential risk for epicardial/valvular inflammation was 
identified from the cardiac histopathology findings in the 39-week dog toxicology study. In 
addition there are 7 important potential risks; some are specific to UCB0942 considering 
nonclinical and clinical data (potential for: withdrawal/dependence, cardiac arrhythmia, 
hepatotoxicity and decreased growth) while the others are class effects (potential for: abuse, 
suicidality, worsening seizures). 
All identified and potential risks, with the exception of decreased growth (applicable only to 
pediatric studies) will be appropriately mitigated in the proposed clinical study. Clinical data 
from this study, from EP0069, and any other relevant data becoming available (such as 
preclinical data) will be reviewed by a DMC that will include internal UCB and external medical 
experts (see Section 11.1.8), to detect and characterize as early as possible any concern(s) related 
to UCB0942 so that Investigators, clinical study subjects, regulatory authorities, and Institutional 
Review Boards/Independent Ethics Committees (IECs) are informed timely and appropriately of 
any significant information that affects the benefit-risk balance of the UCB0942 and 
participation in the study. The specific mitigation measures for cardiac AEs, psychiatric events 
and drug-drug interactions are discussed further below.
Has been changed to: 
The important identified risks based on clinical data include the development of acute psychiatric 
effects and drug-drug interactions (DDIs) with strong cytochrome P450 (CYP) 3A4 enzyme 
inducers leading to decreased exposure levels of UCB0942. There are also some important 
potential risks that are UCB0942-specific based on clinical data, including impairment of 
cognitive and psychomotor performance, DDI between UCB0942 with CYP2C19 substrates 
leading to increased levels of these substrates, and decrease in blood pressure. In addition, there 
are several potential risks for UCB0942 that are class effects or known for other products, 
including suicidality, worsening of seizures, substance abuse and dependence, tolerance to the 
anticonvulsant effects of the drug, and decreased bone mineral density. Finally, there are a 
number of potential risks that are UCB0942-specific based on nonclinical data, including 
epicardial and valvular inflammation and epicardial fibroplasia with administration longer than 
13 weeks, QT prolongation, hepatoxicity, DDI with strong CYP3A4 inhibitors leading to 
increased exposure levels of UCB0942, DDI with strong CYP2C19 inhibitors or inducers 
leading to increased or decreased exposure levels of UCB0942, and growth retardation.
All identified and potential risks, with the exception of decreased growth (applicable only to 
pediatric studies) will be appropriately mitigated in the proposed clinical study. Clinical data 
from the completed study EP0069 have been reviewed by a DMC that included internal UCB 
and external medical experts. Data from this study and any other relevant data that become
available (such as preclinical data) will be reviewed by the DMC in order to detect and 
characterize as early as possible any concern(s) related to UCB0942 (see Section 11.1.8).
Investigators, clinical study subjects, regulatory authorities, and Institutional Review 
Boards/Independent Ethics Committees (IECs) will be informed in a timely manner of any 
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significant information that affects the benefit-risk balance of the UCB0942 and participation in 
the study. The specific mitigation measures for cardiac AEs, psychiatric events and drug-drug 
interactions are discussed further below, and additional details about risks and mitigation 
strategy are provided in Section 6 of the Investigator’s Brochure.
Change #5
Section 2.3.2 Psychiatric adverse events, Paragraph 2 (deletions bolded)
In EP0069, daily psychiatric monitoring is performed in all subjects for the first 2 weeks 
after dosing starts, and weekly thereafter. In the current OLE study, subjects will have a 
psychiatric (BPRS) and cognitive (MMSE) assessment at study visits every 3 months for years 1, 
2 and 3, and every 6 months for years 4 and 5. The CIWA-B will be performed at the LEPV (last 
visit prior to the Taper Period)/EDV, at the visit at the end of the Taper Period) and at SFU1 and 
SFU2 (1 week and 30 days after administration of the final dose of UCB0942, respectively). In 
addition, to further reduce the risk that participating subjects develop psychiatric AEs, subjects 
with a history of psychosis, schizophrenia, bipolar disorder, or severe unipolar depression will be 
excluded from this study. Lastly, based on the fact that titration has been shown to reduce the 
incidence of other AEs and increase the general tolerability of UCB0942, titration may also 
reduce the risk of psychiatric AEs. 
Has been changed to: 
In the current study, subjects will have a psychiatric (BPRS) and cognitive (MMSE) assessment 
at study visits every 3 months for years 1, 2 and 3, and every 6 months for years 4 and 5. The 
CIWA-B will be performed at the LEPV (last visit prior to the Taper Period)/EDV, at the visit at 
the end of the Taper Period) and at SFU1 and SFU2 (1 week and 30 days after administration of 
the final dose of UCB0942, respectively). In addition, to further reduce the risk that participating 
subjects develop psychiatric AEs, subjects with a history of psychosis, schizophrenia, bipolar 
disorder, or severe unipolar depression will be excluded from this study. Lastly, based on the fact 
that titration has been shown to reduce the incidence of other AEs and increase the general 
tolerability of UCB0942, titration may also reduce the risk of psychiatric AEs. 
Change #6
Section 2.3.3 Drug-drug interactions
A drug-drug interaction study in subjects with epilepsy showed that carbamazepine – a strong 
CYP3A4 inducer – reduced UCB0942 plasma exposure by >85%. Therefore, subjects on 
carbamazepine or other strong CYP3A4 inducers (eg, phenytoin, phenobarbital, or primidone) 
will not be enrolled in this study because the plasma exposure may be too low to produce any 
therapeutic benefit.
Has been changed to (change bolded)
A drug-drug interaction study in subjects with epilepsy showed that carbamazepine – a strong 
CYP3A4 inducer – reduced UCB0942 plasma exposure by >85%. Therefore, subjects on 
carbamazepine or other strong CYP3A4 inducers (eg, phenytoin, phenobarbital, or primidone) 
will not be enrolled in this study because the plasma exposure may be too low to produce any 
therapeutic benefit.
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Preclinical data indicate the potential involvement of CYP2C19 in the metabolism of 
UCB0942.While the contribution of CYP2C19 is still unclear regarding the degree to which 
it contributes to the metabolism of UCB0942 or its metabolites, both strong inhibitors and 
inducers of CYP2C19 will also be prohibited. Additionally, in studies with human study 
participants, drug-drug interaction of UCB0942 (perpetrator) with CYP2C19 substrates 
(victims) was observed leading to increased levels of CYP2C19 substrates. Therefore, 
concomitant use of sensitive CYP2C19 substrates will be prohibited in EP0073. If subjects 
are already taking strong inducers or inhibitors or sensitive substrates of CYP2C19 prior 
to Amendment 3, they may continue to do so, but close monitoring should be implemented.
Change #7
Section 5.1 Study description, third paragraph, first bullet, second bullet
(first paragraph only), and first paragraph after the second bullet list
A DMC will systematically monitor and report on the progress, safety, and/or critical efficacy 
endpoints of the study. This includes evaluating the safety signals and benefit-risk balance for 
the study subjects in relationship to new data relevant for the efficacy and safety of the IMP. The 
benefit-risk balance of every subject entering the study will be reviewed by the DMC within 
approximately 3 months after first dosing in EP0073. Voting members of the DMC will include 
external physicians with experience in treating refractory epilepsy and a cardiologist. The DMC 
will make recommendations to the company about continuation of the study, which may include 
changes to study procedures, withdrawal or limiting inclusion of subjects with a negative 
benefit-risk balance, or termination of the clinical study.
The study will consist of:

A 2-week Screening Period from V13 to V15 (Days OP43 to OP57) of the 8-week Outpatient 
Maintenance Period of the EP0069 study. The Screening Visit will be on V13 of EP0069 and 
will be V1 of the current OLE study. At this visit, informed consent will be signed and 
inclusion and exclusion criteria (from the current OLE study) will be checked. The verbatim 
of the attained benefits of treatment with UCB0942, including seizure control, health and 
well-being, and social functioning, declared by a subject/caregiver will be captured as 
narratives and filled in by the Investigator or site personnel. During the Screening Period, the 
Investigator will also provide a statement and a brief justification of positive benefit-risk 
balance for each subject’s participation in EP0073 and long-term treatment with UCB0942. 
These narratives of benefit by the subject/caregiver and the benefit-risk statement and the 
justification by the Investigator will be maintained as source documents and will be reviewed 
by the DMC.

An Evaluation Period of up to approximately 5 years, which will start with V2, the EV, 
which is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of 
EP0069. Eligible subjects will enter EP0073 before the planned dose tapering in EP0069. 
Subjects will be issued and return seizure diaries during each visit. Subjects must be educated 
to record all types of seizures that occur, any illness or injury, and all study medication intake 
in their seizure diary and be educated to complete their diary entries after each seizure or at 
least once a day. Throughout the study, the Investigator also will be requested to periodically 
re-assess and re-confirm that the benefit-risk ratio for the subject of the long-term treatment 
with the IMP, considering the knowledge of the IMP’s efficacy and safety profile and 
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alternative treatment options, remains positive. Narratives of benefit by the subject/caregiver 
and the benefit-risk statement and the justification by the Investigator will be captured in a 
dedicated form at the scheduled time points presented in Table 5-2.
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP0069. They will continue this dose in the current study and there will be no 
tapering from the EP0069 dose before they receive the first dose in EP0073; however, 
throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg (400mg bid); 
intermediate doses will not be allowed except for tapering and titration. Exceptions may be 
allowed after consultation with the UCB Study Physician or PRA Medical Monitor. The dose of 
UCB0942 must always be administered as bid morning and evening doses, approximately 
12 hours apart. The first dose of the current study will be the dose on the evening of V2.
Has been changed to (change bolded):
A DMC will systematically monitor and report on the progress, safety, and/or critical efficacy 
endpoints of the study. This includes evaluating the safety signals and benefit-risk balance for 
the study subjects in relationship to new data relevant for the efficacy and safety of the IMP. The 
benefit-risk balance of every subject entering the study will be reviewed by the DMC within 
approximately 3 months after first dosing in EP0073. Voting members of the DMC will include 
external physicians with experience in treating refractory epilepsy and a cardiologist. The DMC 
will make recommendations to the company about continuation of the study, which may include 
changes to study procedures, or termination of the clinical study.
The study will consist of:

A 2-week Screening Period from V13 to V15 (Days OP43 to OP57) of the 8-week Outpatient 
Maintenance Period of the EP0069 study. The Screening Visit will be on V13 of EP0069 and 
will be V1 of the current OLE study. At this visit, informed consent will be signed and 
inclusion and exclusion criteria (from the current OLE study) will be checked. The verbatim 
of the attained benefits of treatment with UCB0942, including seizure control, health and 
well-being, and social functioning, declared by a subject/caregiver will be captured as 
narratives and filled in by the Investigator or site personnel. During the Screening Period, the 
Investigator will also provide a statement and a brief justification of the benefit-risk balance 
for each subject’s participation in EP0073 and long-term treatment with UCB0942. These 
narratives of benefit by the subject/caregiver and the benefit-risk statement and the 
justification by the Investigator will be maintained as source documents and will be reviewed 
by the DMC.

An Evaluation Period of up to approximately 5 years, which will start with V2, the EV, 
which is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of 
EP0069. Eligible subjects will enter EP0073 before the planned dose tapering in EP0069. 
Subjects will be issued and return seizure diaries during each visit. Subjects must be educated 
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to record all types of seizures that occur, any illness or injury, and all study medication intake 
in their seizure diary and be educated to complete their diary entries after each seizure or at 
least once a day. Throughout the study, the Investigator also will be requested to periodically 
re-assess and re-confirm that the benefit-risk ratio for the subject on long-term treatment with 
the IMP, considering the knowledge of the IMP’s efficacy and safety profile and alternative 
treatment options, justifies continuation in the study. Narratives of benefit by the 
subject/caregiver and the benefit-risk statement and the justification by the Investigator will 
be captured in a dedicated form at the scheduled time points presented in Table 5-2.
Subjects being enrolled in the current study from EP0069 will enter EP0073 on the dose they 
received in EP0069. They will continue this dose in the current study and there will be no 
tapering from the EP0069 dose before they receive the first dose in EP0073; however, 
throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg (400mg bid); 
intermediate doses will not be allowed except for tapering and titration. Exceptions may be 
allowed after consultation with the PRA Medical Monitor. The dose of UCB0942 must always 
be administered as bid morning and evening doses, approximately 12 hours apart. The first dose 
of the current study will be the dose on the evening of V2.
Change #8
Section 5.3 Schedule of study assessments, Table 5-2, footnote d
d  No echocardiogram will be done at V3.
Has been changed to (change bolded):
d  No echocardiogram will be done at V3, V14, and V16.
Change #9
Section 5.4 Rationale for study design and selection of dose, final 
paragraph
Throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg (400mg bid); 
intermediate doses will not be allowed except for tapering and titration unless agreed by the 
UCB Study Physician or PRA Medical Monitor.
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Has been changed to (change bolded):
Throughout the Evaluation Period, the Investigator will be allowed to increase or decrease the 
dose of UCB0942 to optimize tolerability and seizure control for each subject. Increases or 
decreases to the dose of UCB0942 should be made in steps not exceeding 200mg/day per week; 
an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is allowed. A faster 
decrease of the dose than 200mg/day per week is allowed when it is clinically appropriate in the 
Investigator's medical judgment. Daily UCB0942 doses during this study may be 100mg (50mg 
bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg (400mg bid); 
intermediate doses will not be allowed except for tapering and titration unless agreed by the 
PRA Medical Monitor.
Change #10
Section 6.3 Withdrawal criteria, third paragraph and Withdrawal Criterion #1
Investigators should contact the UCB Study Physician or PRA Medical Monitor, whenever 
possible, to discuss the withdrawal of a subject in advance.
Subjects must be withdrawn from the study if any of the following events occur:
1. Withdrawal for safety reasons by the Investigator and/or when the benefit-risk ratio of the 
IMP treatment is considered negative.
Has been changed to (change bolded):
Investigators should contact the PRA Medical Monitor, whenever possible, to discuss the 
withdrawal of a subject in advance.
Subjects must be withdrawn from the study if any of the following events occur:
1. Withdrawal for safety reasons by the Investigator and/or when the benefit-risk ratio of the 
IMP treatment is 0 to 4 (on a scale from 0 to 10), indicating the risks outweigh the 
benefits.
Change #11
Section 7.1 Description of investigational medicinal product(s)
The details of the UCB0942 IMP are displayed in Table 7-1. 
Table 7-1: Description of investigational medicinal product
UCB0942 25mg
UCB0942 100mg
UCB0942 200mg
Dosage form
White, film-coated 
tablet
White, film-coated 
tablet
White, film-coated 
tablet
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UCB0942 25mg
UCB0942 100mg
UCB0942 200mg
Manufacturers
Aptuit (Verona) S.r.l.
Via Flemming 4
37135 Verona
Italy
Catalent Micron Technologies
Crossways Boulevard
Crossways Dartford, Kent
DA2 6QY United Kingdom
Batch/lot number
Will be assigned according to GMP
Expiry date
Will be assigned according to GMP
GMP=Good Manufacturing Practice; IRT=interactive response technology
Note: UCB0942 tablets will be provided in bottles, containing 135 tablets for the 25mg dosage and either 80 or 
200 tablets for both the 100mg and 200mg dosage. Appropriate bottle size will be dispensed through the IRT system 
as per visit schedule and visit interval.
Note: 100 and 200mg tablets are the same size and appearance.
Has been changed to: 
The table has been deleted and replaced with the following sentence: 
The IMP is supplied as white, film-coated tablets in strengths of 25mg, 100mg, and 200mg. 
Change #12
Section 7.2 Treatments to be administered, first and third paragraphs
Subjects being enrolled in the current study from EP0069 will continue their dose in the current 
study and there will be no tapering from the EP0069 dose before they receive the first dose in 
EP0073; however, throughout the Evaluation Period, the Investigator will be allowed to increase 
or decrease the dose of UCB0942 to optimize tolerability and seizure control for each subject. 
Increases or decreases to the dose of UCB0942 should be made in steps not exceeding 
200mg/day per week; an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is 
allowed. A faster decrease of the dose than 200mg/day per week is allowed when it is clinically 
appropriate in the Investigator's medical judgment. Daily UCB0942 doses during this study may 
be 100mg (50mg bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration unless 
agreed by the UCB Study Physician or PRA Medical Monitor. The dose of UCB0942 must 
always be administered as bid morning and evening doses, approximately 12 hours apart. The 
first dose of the current study will be the dose on the evening of V2.
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. The UCB Study Physician or PRA Medical Monitor must 
be consulted prior to initiation of concomitant AED withdrawal. New concomitant AEDs may be 
introduced to optimize tolerability and seizure reduction, if the concomitant medication has been 
approved for focal seizures by the health authority of the subject’s country of residence, taking 
the drug-to-drug interactions profile of UCB0942 into account. New AEDs (with the exception 
of AEDs listed in the prohibited medication section, Section 7.8.2) should be added only when 
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the subject has not optimally or adequately responded to a maximum tolerated dose of 
UCB0942.
Has been changed to (change bolded):
Subjects being enrolled in the current study from EP0069 will continue their dose in the current 
study and there will be no tapering from the EP0069 dose before they receive the first dose in 
EP0073; however, throughout the Evaluation Period, the Investigator will be allowed to increase 
or decrease the dose of UCB0942 to optimize tolerability and seizure control for each subject. 
Increases or decreases to the dose of UCB0942 should be made in steps not exceeding 
200mg/day per week; an exception is Taper Week 1 where a step of 800mg/day to 500mg/day is 
allowed. A faster decrease of the dose than 200mg/day per week is allowed when it is clinically 
appropriate in the Investigator's medical judgment. Daily UCB0942 doses during this study may 
be 100mg (50mg bid), 200mg (100mg bid), 400mg (200mg bid), 600mg (300mg bid), or 800mg 
(400mg bid); intermediate doses will not be allowed except for tapering and titration unless 
agreed by the PRA Medical Monitor. The dose of UCB0942 must always be administered as 
bid morning and evening doses, approximately 12 hours apart. The first dose of the current study 
will be the dose on the evening of V2.
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. The PRA Medical Monitor must be consulted prior to 
initiation of concomitant AED withdrawal. New concomitant AEDs may be introduced to 
optimize tolerability and seizure reduction, if the concomitant medication has been approved for 
focal seizures by the health authority of the subject’s country of residence, taking the 
drug-to-drug interactions profile of UCB0942 into account. New AEDs (with the exception of 
AEDs listed in the prohibited medication section, Section 7.8.2) should be added only when the 
subject has not optimally or adequately responded to a maximum tolerated dose of UCB0942.
Change #13
Section 7.3 Packaging
UCB0942 tablets will be provided in bottles, containing 135 tablets for the 25mg dosage and 
either 80 or 200 tablets for both the 100mg and 200mg dosage. Appropriate bottle size will be 
dispensed through the IRT system as per visit schedule and visit interval.
Has been changed to: 
UCB0942 tablets are manufactured, packaged and labeled according to Good Manufacturing 
Practice (GMP) guidelines and applicable laws or regulations. The IMP is suitably packaged in 
such a way to protect the IMP from deterioration during transport and storage. Packaging details 
are included in the IMP Handling Manual.
Change #14
Section 7.5 Handling and storage requirements
The Investigator (or designee) is responsible for the safe and proper storage of UCB0942 at the 
site. Investigational medicinal product stored by the Investigator (or designee) is to be kept in a 
secured area with limited access.
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Appropriate storage conditions must be ensured either by controlled room temperature or by 
completion of a temperature log in accordance with local requirements on a regular basis 
(eg, once a week), showing minimum and maximum temperatures reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately communicated to the 
Clinical Project Manager (CPM) (or designee) and feedback must be received before further use 
of UCB0942.
The CPM (or designee) will transmit the out-of-range temperature (copy of the temperature log 
and duration of the out-of-range temperature) to the Clinical Supply Manager. Based on
discussion with a UCB Quality Assurance representative, the Clinical Supply Manager will then 
provide the CPM (or designee) with instructions for the site regarding the use of UCB0942.
The Investigator (or designee) will instruct the subject to store UCB0942 following the 
instructions on the label.
Has been changed to: 
TheInvestigator (or designee) is responsible for the safe and proper storage of UCB0942 at the 
site. Investigational medicinal product stored by the Investigator is to be kept in a secured area 
with limited access according to the storage conditions mentioned on the label.
Appropriate storage conditions must be ensured either by controlling the temperature (eg, room, 
refrigeration unit) or by completion of a temperature log in accordance with local requirements 
on a regular basis (ie, every working day), showing actual and minimum/maximum temperatures 
reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
and IMP information contained in the IMP Handling Manual. The Investigator (or designee) will 
instruct the subject to store the IMP following the instructions on the label.
Change #15
Section 7.8.1 Permitted concomitant treatments (medications and 
therapies), first bullet

All subjects will enter EP0073 using their current AED regimen. Concomitant AEDs and 
AED dose(s), or VNS settings may be adjusted throughout EP0073 as per the Investigator’s 
clinical judgment based on tolerability and seizure control for each individual subject. 
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. New concomitant AEDs may be introduced to 
optimize tolerability and seizure reduction. Changes in AEDs should be discussed with the 
UCB Study Physician or PRA Medical Monitor on an individual and case-by-case basis.
Has been changed to (change bolded):

All subjects will enter EP0073 using their current AED regimen. Concomitant AEDs and 
AED dose(s), or VNS settings may be adjusted throughout EP0073 as per the Investigator’s 
clinical judgment based on tolerability and seizure control for each individual subject. 
Concomitant AED(s) may be carefully tapered and discontinued to achieve UCB0942 
monotherapy, if clinically appropriate. New concomitant AEDs may be introduced to 
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optimize tolerability and seizure reduction. Changes in AEDs should be discussed with the 
PRA Medical Monitor on an individual and case-by-case basis.
Change #16
Section 7.8.2 Prohibited concomitant treatments (medications and 
therapies)
The following concomitant medications are prohibited during the study (this is not a complete 
list of prohibited medications):

Carbamazepine, phenytoin, phenobarbital, primidone, or other AEDs that are strong 
CYP3A4 inducers

Benzodiazepines taken >3 times per week (ie, >3 doses within 7 days)

Zolpidem, zaleplon, or zopiclone taken >3 times per week

Tiagabine

Felbamate

Vigabatrin

Strong non-AED CYP3A4 inducers/inhibitors (ie, prescription drugs, nonprescription drugs, 
dietary [eg, grapefruit or passion fruit], or herbal products)
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInter
actionsLabeling/ucm093664.htm)
Has been changed to (change bolded): 
The following concomitant medications are prohibited during the study (this is not a complete 
list of prohibited medications):

Carbamazepine, phenytoin, phenobarbital, primidone, or other AEDs that are strong 
CYP3A4 inducers

Benzodiazepines taken >3 times per week (ie, >3 doses within 7 days)

Zolpidem, zaleplon, or zopiclone taken >3 times per week

Tiagabine

Felbamate

Vigabatrin

Strong non-AED CYP3A4 inducers/inhibitors (ie, prescription drugs, nonprescription drugs, 
dietary [eg, grapefruit or passion fruit], or herbal products)
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInter
actionsLabeling/ucm093664.htm)
The following medications* should not be administered concomitantly with UCB0942. 
However, if subjects are already taking these medications prior to Amendment 3, they may 
continue to do so, but close monitoring should be implemented. 

Strong CYP2C19 inhibitors (eg, fluconazole, fluoxetine, fluvoxamine, and ticlopidine)
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
Strong CYP2C19 inducers (eg, including rifampicin and ritonavir)

CYP2C19 sensitive substrates (eg, s-mephenytoin and omeprazole)
*For more details refer to Table 3-1, Table 3-2, and Table 3-3 in FDA Drug Development 
Resources, Drug development and drug interactions: Table of substrates, inhibitor and 
inducers.
Change #17
Section 8.2.3 Minimal Evaluation Visit, echocardiogram assessments

Echocardiogram (not at V3)
Has been changed to (change bolded):

Echocardiogram (not at V3, V14, and V16)
Change #18
Section 11.1.8 Safety signal detection, third paragraph
Any findings from this review will be brought to the attention of the DMC, that will 
systematically monitor and report on the progress, safety, and/or critical efficacy endpoints of the 
study by convening to review the ongoing program safety and efficacy data. This includes 
evaluating the safety signals and benefit-risk balance for the study subjects in relationship with 
new data relevant for IMP efficacy and safety. The benefit-risk balance of every subject entering 
the study will be reviewed by the DMC within approximately 3 months after first dosing in 
EP0073. Voting members of the DMC will include external physicians with experience in 
treating refractory epilepsy and a cardiologist. The DMC will make recommendations to the 
company about continuation of the study, which may include changes to study procedures, 
withdrawal or limiting inclusion of subjects with a negative benefit-risk balance, or termination 
of the clinical study. The precise membership, scope, and responsibilities of the DMC are 
described in the DMC Charter.
Has been changed to (change bolded):
Any findings from this review will be brought to the attention of the DMC, that will 
systematically monitor and report on the progress, safety, and/or critical efficacy endpoints of the 
study by convening to review the ongoing program safety and efficacy data. This includes 
evaluating the safety signals and benefit-risk balance for the study subjects in relationship with 
new data relevant for IMP efficacy and safety. The benefit-risk balance of every subject entering 
the study will be reviewed by the DMC within approximately 3 months after first dosing in 
EP0073. Voting members of the DMC will include external physicians with experience in 
treating refractory epilepsy and a cardiologist. The DMC will make recommendations to the 
company about continuation of the study, which may include changes to study procedures, or 
termination of the clinical study. The precise membership, scope, and responsibilities of the 
DMC are described in the DMC Charter.
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Change #19
Section 11.3 Adverse events of special interest, a link to the section 
describing PDILI has been added 
Guidance on the evaluation and management of PDILI is provided in Section 11.6.1.
Change #20
Section 11.4 Immediate reporting of adverse events, adverse events of 
special interest has been added

Adverse events of special interest (see Section 11.3)
Change #21
Section 11.7.3 Echocardiogram, paragraph after numbered list
Images will be recorded and stored digitally and retained if further analysis is needed. Central 
reading of the echocardiograms may be performed by a specialized vendor.
Has been changed to (change bolded):
Images will be recorded and stored digitally and retained if further analysis is needed. In the 
event that echocardiograms are not interpretable during the study, alternative assessments 
using either transesophageal echocardiography or cardiac magnetic resonance imaging 
(CMR) should be performed. Central reading of the echocardiograms may be performed by a 
specialized vendor.
Change #22
Section 11.7.8 Narratives of benefit and benefit-risk assessment 
Narratives of benefit by the subject/caregiver and the benefit-risk statement and the justification 
by the Investigator will be captured in a dedicated form during the Screening Period and at other 
scheduled time points presented in Table 5-2. The verbatim of the attained benefits or treatment 
with UCB0942, including seizure control, health and well-being, and social functioning, declared 
by a subject/caregiver will be recorded as narratives by the Investigator or site personnel. The 
Investigator will also assess and provide a brief justification that the benefit-risk ratio for the 
subject of the long-term treatment with the IMP remains positive, considering the knowledge of 
the IMP’s efficacy and safety profile and alternative treatment options.
Has been changed to (change bolded):
Narratives of benefit by the subject/caregiver and the benefit-risk statement and the justification 
by the Investigator will be captured in a dedicated form during the Screening Period and at other 
scheduled time points presented in Table 5-2. The verbatim of the attained benefits or treatment 
with UCB0942, including seizure control, health and well-being, and social functioning, declared 
by a subject/caregiver will be recorded as narratives by the Investigator or site personnel. The 
Investigator will also assess and provide a brief justification that the benefit-risk ratio for the 
subject on long-term treatment with the IMP supports continuation in the study, considering 
the knowledge of the IMP’s efficacy and safety profile and alternative treatment options.
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Change #23
Section 12.4 Termination of the study, first paragraph
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, negative 
benefit-risk balance, or unsatisfactory enrollment with respect to quality or quantity.
Has been changed to (change bolded):
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, benefit-risk 
balance (0 to 4) indicating the risks outweigh the benefits, or unsatisfactory enrollment with 
respect to quality or quantity.
Change #24
Section 13.1 Definition of analysis sets, PK analysis set has been added
The Pharmacokinetic Per-Protocol Set will consist of subjects in the FAS who received at least 
1 dose of study medication, and did not have a major protocol deviation impacting the PK 
variables.
Change #25
Section 13.8 Planned interim analysis and data monitoring, first and 
second paragraphs 
A DMC will systematically monitor and report (at least quarterly up to the time point when the 
last patient entering EP0073 reaches 1 year in the study, and less frequent thereafter) on the 
progress, safety, and/or critical efficacy endpoints of this study by convening to review the 
ongoing program safety and efficacy data. This includes evaluating the safety signals and 
benefit-risk balance for the study subjects in relationship to new data relevant for IMP efficacy 
and safety. The benefit-risk balance of every subject entering the study will be reviewed by the 
DMC approximately 3 months after first dosing in EP0073. Blinded data until database lock 
from EP0069 and data from the OLE EP0073 studies will be reviewed in order for the DMC to 
provide an ongoing risk-benefit evaluation with particular reference to the occurrence of 
psychiatric and cardiological/cardiovascular AEs, seizure control, and any new identified safety 
signals. Voting members of the DMC will include external physicians with experience in treating 
refractory epilepsy and a cardiologist, none of whom will be involved with the conduct of the 
study, either by management or participation. In addition, there will be an independent reporting 
team, consisting of an independent statistician and independent statistical programmers, who will 
be completely independent from the blinded reporting team. The blinded reporting team will be 
responsible for all operational aspects of the study, including routine monitoring and cleaning of 
the data, programming, and quality control of all analyses defined in the interim EP0073 SAP on 
blinded data of EP0069 and unblinded data of EP0073 (open-label study). If required for 
monitoring of safety and benefit-risk of EP0073 patients, unblinded data from EP0069 study can 
be reviewed by the external members of the DMC at closed sessions and provided by an 
independent statistician. The DMC will make recommendations to the company, which may 
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include changes to study procedures, withdrawal of subjects with a negative risk balance, or 
termination of the clinical study. 
A DMC Charter will define the composition, roles, and responsibilities of the DMC, specify the 
data to be reviewed and the periodicity of data review, and determine the procedures to be 
followed to maximize subject safety and ensure positive benefit-risk balance of participation in 
the study. 
Has been changed to (change bolded):
A DMC will systematically monitor and report (at least quarterly up to the time point when the 
last patient entering EP0073 reaches 1 year in the study, and less frequent thereafter) on the 
progress, safety, and/or critical efficacy endpoints of this study by convening to review the 
ongoing program safety and efficacy data. This includes evaluating the safety signals and 
benefit-risk balance for the study subjects in relationship to new data relevant for IMP efficacy 
and safety. The benefit-risk balance of every subject entering the study will be reviewed by the 
DMC approximately 3 months after first dosing in EP0073. Blinded data until database lock 
from EP0069 and data from the OLE EP0073 studies will be reviewed in order for the DMC to 
provide an ongoing risk-benefit evaluation with particular reference to the occurrence of 
psychiatric and cardiological/cardiovascular AEs, seizure control, and any new identified safety 
signals. Voting members of the DMC will include external physicians with experience in treating 
refractory epilepsy and a cardiologist, none of whom will be involved with the conduct of the 
study, either by management or participation. In addition, there will be an independent reporting 
team, consisting of an independent statistician and independent statistical programmers, who will 
be completely independent from the blinded reporting team. The blinded reporting team will be 
responsible for all operational aspects of the study, including routine monitoring and cleaning of 
the data, programming, and quality control of all analyses defined in the interim EP0073 SAP on 
blinded data of EP0069 and unblinded data of EP0073 (open-label study). If required for 
monitoring of safety and benefit-risk of EP0073 patients, unblinded data from EP0069 study can 
be reviewed by the external members of the DMC at closed sessions and provided by an 
independent statistician. The DMC will make recommendations to the company, which may 
include changes to study procedures, or termination of the clinical study. 
A DMC Charter will define the composition, roles, and responsibilities of the DMC, specify the 
data to be reviewed and the periodicity of data review, and determine the procedures to be 
followed to maximize subject safety and ensure that the benefit-risk balance justifies 
participation in the study.
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18
DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by 
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Investigator:
Printed name
Date/Signature
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19
DECLARATION AND SIGNATURE OF COORDINATING 
INVESTIGATOR (GERMANY)
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by 
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Coordinating Investigator (Germany):
_____________________________
Date/Signature
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20
DECLARATION AND SIGNATURE OF COORDINATING 
INVESTIGATOR 
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by 
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Coordinating Investigator:
_____________________________
Date/Signature
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21
SPONSOR DECLARATION
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice.
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ELECTRONIC SIGNATURES 
 
Signed by 
Meaning of Signature 
Server Approval Date 
(dd-mon-yyyy 
(HH:mm)) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EP0073 Protocol Amendment 3
Clinical Approval
14-Nov-2017 15:57 GMT+0
Clinical Approval
14-Nov-2017 15:59 GMT+0
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SAP_001.pdf: 
UCB 
 
09 Oct 2020 
Statistical Analysis Plan 
Padsevonil (UCB0942) 
EP0073 
 
 
 
Confidential 
Page 1 of 73 
STATISTICAL ANALYSIS PLAN  
Study: EP0073 
Product: Padsevonil (UCB0942) 
AN OPEN-LABEL, MULTICENTER, EXTENSION STUDY TO EVALUATE THE 
LONG-TERM SAFETY, TOLERABILITY, AND EFFICACY OF UCB0942 WHEN 
USED AS ADJUNCTIVE THERAPY FOR PARTIAL-ONSET SEIZURES IN ADULT 
SUBJECTS WITH HIGHLY DRUG-RESISTANT FOCAL EPILEPSY 
 
SAP/Amendment Number Date 
Final SAP 
16 Feb 2016  
Amendment 1 
26 Aug 2019 
Amendment 2 
09 Oct 2020 
 
 
Confidentiality Statement 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, reproduced, 
published, or otherwise used without the express permission of UCB. 
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Statistical Analysis Plan 
Padsevonil (UCB0942) 
EP0073 
 
 
 
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Page 2 of 73 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... 5 
1 
INTRODUCTION ............................................................................................................. 8 
2 
PROTOCOL SUMMARY ................................................................................................. 8 
2.1 Study objectives ................................................................................................................. 8 
2.1.1 
Primary objective ................................................................................................... 8 
2.1.2 
Secondary objectives ............................................................................................. 8 
2.1.3 
Exploratory Objectives .......................................................................................... 8 
2.2 Study variables ................................................................................................................... 8 
2.2.1 
Safety variables ...................................................................................................... 8 
2.2.1.1 
Primary safety variable ................................................................................ 8 
2.2.1.2 
Other safety variables .................................................................................. 8 
2.2.2 
Efficacy variables .................................................................................................. 9 
2.2.2.1 
Primary efficacy variable ............................................................................ 9 
2.2.2.2 
Secondary efficacy variables ....................................................................... 9 
2.2.2.3 
Exploratory pharmacokinetic variable ...................................................... 10 
2.3 Study design and conduct ................................................................................................ 10 
2.4 Determination of sample size ........................................................................................... 12 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 12 
3.1 General presentation of summaries and analyses ............................................................ 12 
3.2 General study level definitions ........................................................................................ 13 
3.2.1 
Analysis periods ................................................................................................... 13 
3.2.2 
First and last dose of UCB0942 ........................................................................... 14 
3.2.3 
Relative day ......................................................................................................... 14 
3.2.4 
Monthly time intervals ......................................................................................... 15 
3.2.5 
Last Value during the On-Treatment Period........................................................ 15 
3.2.6 
Completer Cohort ................................................................................................ 15 
3.2.7 
Mapping of data from early discontinuation visits .............................................. 16 
3.3 Definition of Baseline values ........................................................................................... 16 
3.4 Protocol deviations ........................................................................................................... 16 
3.5 Analysis sets ..................................................................................................................... 16 
3.5.1 
Enrolled Set ......................................................................................................... 16 
3.5.2 
Safety Set ............................................................................................................. 17 
3.5.3 
Full Analysis Set .................................................................................................. 17 
3.5.4 
Pharmacokinetic Per-Protocol Set ....................................................................... 17 
3.6 Treatment assignment and treatment groups ................................................................... 17 
3.7 Center pooling strategy .................................................................................................... 17 
3.8 Coding dictionaries .......................................................................................................... 17 
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3.9 Changes to protocol-defined analyses.............................................................................. 17 
3.10 Definition of study-specific derived variables ................................................................. 17 
3.10.1 
Seizure frequency related variables ..................................................................... 17 
3.10.1.1 
Seizure frequency ...................................................................................... 17 
3.10.1.2 
Percent reduction in seizure frequency...................................................... 18 
3.10.1.3 
XX% Responder Rate in focal seizure frequency ..................................... 18 
3.10.2 
Seizure freedom ................................................................................................... 18 
3.10.3 
Seizure-free days ................................................................................................. 19 
3.10.4 
Patient Weighted Quality of Life in Epilepsy Inventory ..................................... 19 
4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 20 
4.1 Adjustments for covariates............................................................................................... 20 
4.2 Handling of dropouts or missing data .............................................................................. 20 
4.2.1 
Seizure diary ........................................................................................................ 20 
4.2.2 
QOLIE-31-P ........................................................................................................ 20 
4.2.3 
Partial/Missing Data for adverse events and concomitant medications: ............. 20 
4.3 Interim analyses and data monitoring .............................................................................. 21 
4.4 Multicenter studies ........................................................................................................... 22 
4.5 Multiple comparisons/multiplicity ................................................................................... 22 
4.6 Use of an efficacy subset of subjects ............................................................................... 22 
4.7 Active-control studies intended to show equivalence ...................................................... 22 
4.8 Examination of subgroups ............................................................................................... 22 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 22 
5.1 Subject disposition ........................................................................................................... 22 
5.2 Protocol deviations ........................................................................................................... 22 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 23 
6.1 Demographics .................................................................................................................. 23 
6.2 Medical history and concomitant diseases ....................................................................... 23 
6.2.1 
History of epilepsy ............................................................................................... 23 
6.3 Other Baseline Characteristics ......................................................................................... 24 
6.4 Concomitant medications ................................................................................................. 25 
6.4.1 
Non- Antiepileptic drugs ..................................................................................... 25 
6.4.2 
Concomitant AEDs .............................................................................................. 25 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 25 
8 
EFFICACY ANALYSES ................................................................................................ 25 
8.1 Statistical analysis of the primary efficacy variable ........................................................ 25 
8.1.1 
Supportive analysis .............................................................................................. 26 
8.2 Statistical analysis of the secondary efficacy variables ................................................... 26 
8.2.1 
Observable focal-onset seizure frequency ........................................................... 26 
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Statistical Analysis Plan 
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EP0073 
 
 
 
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8.2.2 
Focal-onset seizure frequency by seizure type .................................................... 26 
8.2.3 
Percent reduction in focal-onset seizure frequency ............................................. 26 
8.2.4 
50%RR on percent reduction in 28-day observable focal-onset seizure frequency26 
8.2.5 
Percentage of seizure free days ............................................................................ 26 
8.2.6 
Seizure freedom ................................................................................................... 26 
8.2.7 
Quality of Life ..................................................................................................... 26 
8.2.8 
Time to discontinuation ....................................................................................... 27 
9 
PHARMACOKINETICS ................................................................................................. 27 
9.1 Plasma concentrations ...................................................................................................... 27 
9.2 Population pharmacokinetics ........................................................................................... 27 
10 SAFETY ANALYSES ..................................................................................................... 28 
10.1 Extent of exposure ........................................................................................................... 28 
10.2 Adverse events ................................................................................................................. 28 
10.2.1 
Definition of treatment-emergent AE .................................................................. 29 
10.2.2 
General summaries of TEAEs ............................................................................. 29 
10.3 Clinical laboratory evaluations ........................................................................................ 30 
10.3.1 
Subjects with potential drug-induced liver injury (PDILI) .................................. 31 
10.4 Vital signs, physical findings, and other observations related to safety .......................... 31 
10.4.1 
Vital signs ............................................................................................................ 31 
10.4.2 
Electrocardiograms .............................................................................................. 32 
10.4.3 
Doppler echocardiography ................................................................................... 32 
10.4.4 
Physical examination ........................................................................................... 32 
10.4.5 
Columbia-Suicide Severity Rating Scale ............................................................. 32 
10.4.6 
Neurological examination .................................................................................... 32 
10.4.7 
Psychiatric and cognition assessment, and withdrawal monitoring .................... 33 
10.4.8 
Employment and living status and epilepsy surgery status ................................. 33 
11 REFERENCES ................................................................................................................ 34 
12 APPENDICES ................................................................................................................. 35 
12.1 PCST Criteria for Hematology, Serum Chemistry and Urinalysis Parameters ............... 35 
12.1.1 
Hematology .......................................................................................................... 35 
12.1.2 
Blood chemistry ................................................................................................... 38 
12.1.3 
Urinalysis ............................................................................................................. 43 
12.2 VITAL SIGN ASSESSMENTS - ABNORMAL ............................................................. 44 
12.3 ELECTROCARDIOGRAM (ECG) – ABNORMAL ...................................................... 46 
13 AMENDMENT(S) TO THE SAP ................................................................................... 47 
13.1 Amendment 1 ................................................................................................................... 47 
13.2 Amendment 2 ................................................................................................................... 65 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ..................................................... 73 
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EP0073 
 
 
 
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LIST OF ABBREVIATIONS 
50%RR 
50% responder rate 
75%RR 
75% responder rate 
AE 
adverse event 
AED 
antiepileptic drug 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BMI 
body mass index 
BP 
blood pressure 
BPRS 
Brief Psychiatric Rating Scale 
BUN 
blood urea nitrogen 
CI 
confidence interval 
CIWA-B 
Clinical Institute Withdrawal Assessment-Benzodiazepines 
CRO 
contract research organization 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CSR 
clinical study report 
DBP 
Diastolic blood pressure 
DMC 
Data Monitoring Committee  
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDV 
early discontinuation visit 
ES 
enrolled set 
EV 
entry visit 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FEV 
full evaluation visit 
FV 
final visit 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
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Statistical Analysis Plan 
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EP0073 
 
 
 
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ILAE 
International League Against Epilepsy  
IMP 
investigational medicinal product 
IPD 
important protocol deviations 
LDH 
lactate dehydrogenase 
LEPV 
Last Evaluation Period Visit 
LEV 
levetiracetam 
LOCF 
last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEV 
minimal evaluation visit 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MMSE 
mini-mental state examination 
n 
number of observations 
OLE 
Open Label Extension study 
PCST 
potentially clinical significant treatment-emergent 
PDILI 
potential drug-induced liver injury 
PK-PPS 
Pharmacokinetic Per-Protocol Set 
POS 
partial-onset seizure 
PR 
pulse rate 
PT 
preferred term 
QOLIE-31-P 
Quality of Life Inventory in Epilepsy-31-P 
QTcB 
QT interval corrected for heart rate using Bazett’s formula 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RBC 
red blood cells 
SAE 
serious adverse event 
SAP 
Statistical analysis plan 
SBP 
systolic blood pressure 
SD 
standard deviation 
SFU 
Safety Follow-up 
SOC 
system organ class 
SS 
Safety Set 
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EP0073 
 
 
 
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Page 7 of 73 
ULN 
upper limit of normal 
VNS 
vagus nerve stimulation 
WBC 
white blood cell 
WHODD 
World Health Organization Drug Dictionary 
YEV 
year evaluation visit 
 
 
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Statistical Analysis Plan 
Padsevonil (UCB0942) 
EP0073 
 
 
 
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Page 8 of 73 
1 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to provide all information that is necessary 
to perform the required statistical analysis of data collected in EP0073. It also defines the 
summary tables, listings, and figures to be included in the final Clinical Study Report (CSR) 
according to the protocol. 
This SAP is based upon, and assumes familiarity, with the following study documents: 
• 
Final Protocol: 11 June 2015 
• 
Protocol Amendment 1: 10 December 2015 
• 
Protocol Amendment 2: 14 November 2016 
• 
Protocol Amendment 3: 09 November 2017 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
The primary objective is to evaluate the long-term safety and tolerability of UCB0942 at 
individualized doses between 100mg/day to a maximum of 800mg/day in subjects with highly 
drug-resistant focal epilepsy. 
2.1.2 
Secondary objectives 
The secondary objectives are: 
• To evaluate the long-term efficacy of UCB0942. 
• To evaluate the effects of UCB0942 on the subject’s quality of life. 
2.1.3 
Exploratory Objectives 
The exploratory objective is to evaluate the plasma concentrations of UCB0942 and metabolites. 
2.2 
Study variables 
2.2.1 
Safety variables 
2.2.1.1 
Primary safety variable 
Occurrence of adverse events (AEs) reported by the subject and/or caregiver or observed by the 
Investigator or clinical site staff beginning at the entry visit (EV) of the Evaluation Period during 
the EP0073 study. 
2.2.1.2 
Other safety variables 
• Changes from EP0069 Baseline in laboratory tests (including hematology, blood chemistry, 
urinalysis) at each assessment during the EP0073 study 
• Changes from EP0069 Baseline in 12-lead electrocardiogram (ECG) parameters at each 
assessment during the EP0073 study 
• Changes from EP0069 Baseline in psychiatric assessments as assessed with the BPRS at each 
assessment during the EP0073 study 
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• Changes from EP0069 baseline in memory or cognition as assessed with the Mini-Mental 
State Examination (MMSE) at each assessment during the EP0073 study 
• Changes in withdrawal symptoms using Clinical Institute Withdrawal 
Assessment- Benzodiazepines (CIWA-B) from the LEPV (last visit prior to the Taper 
Period), at each assessment during the Taper Period (visit at the end of the Taper Period) and 
during the safety follow-up (SFU) Period (visits at 1 week and 30 days after administration 
of the final dose of UCB0942) of the EP0073 study 
• Changes from EP0069 Baseline in vital sign parameters (pulse rate, blood pressure [BP], and 
respiratory rate) at each assessment during the EP0073 study 
• Occurrence of a clinically concerning valvular or pericardial effusion change or other 
clinically significant abnormalities as identified by 2-dimensional Doppler echocardiography 
at each assessment during the EP0073 study 
• Changes from EP0069 Baseline in physical examination (including body weight)  
• Neurological examination findings at each assessment during the EP0073 study 
2.2.2 
Efficacy variables 
In both this study and EP0069 only partial-onset seizures (POS) of type IA1, IB, and IC and not 
non-motor IA2, IA3 or IA4 seizures will be counted for the assessment of seizure frequency and 
responder rate. For assessment of seizure-free rate and days, all seizure types will be considered. 
2.2.2.1 
Primary efficacy variable 
The primary efficacy variable is the 75% responder rate (75%RR) by 3-month intervals over the 
Evaluation Period.  
A 75% responder is defined as a subject with a ≥75% reduction in POS frequency relative to the 
EP0069 2-week Prospective Outpatient Baseline Period (consisting of 2 to 3 weeks of 
prospective post-screening subject diary seizure counts). 
2.2.2.2 
Secondary efficacy variables 
The secondary efficacy variables are: 
• Median POS frequency per 28 days by 3-month intervals over the Evaluation Period of 
the EP0073 study. 
• Median POS frequency per 28 days by seizure type by 3-month intervals over the 
Evaluation Period of the EP0073 study. 
• Percent reduction in POS frequency relative to the EP0069 2-week Prospective 
Outpatient Baseline Period by 3-month intervals over the Evaluation Period of the 
EP0073 study. 
• The 50% responder rate (50% RR) by 3-month intervals over the Evaluation Period of the 
EP0073 study. A 50% responder is defined as a subject with a ≥50% reduction in POS 
frequency relative to the EP0069 2-week Prospective Outpatient Baseline Period. 
• Percentage of seizure-free days by 3-month intervals over the Evaluation Period. 
• Seizure-free rate by 3-month intervals over the Evaluation Period.  
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• 
Changes in QOLIE-31-P scores from V3 of EP0069 through the assessment of the 
Evaluation Period. 
2.2.2.3 
Exploratory pharmacokinetic variable 
Plasma concentrations of UCB0942 and its metabolites (
and 
) will be measured during the first 13 months of treatment in EP0073 (at V3, 
V4, V5, V6, V7, V8, and V9). 
2.3 
Study design and conduct 
EP0073 is a multicenter, open-label extension (OLE) study that will run throughout the clinical 
development period of UCB0942 and will continue for approximately 5 years or until either a 
marketing authorization is granted by any health authority for the adjunctive treatment for POS 
in adult subjects with highly drug-resistant focal epilepsy, or until UCB decides to close the 
study due to termination of the development program.  
Subjects who experience substantial benefit from UCB0942 with acceptable tolerability in 
EP0069 may have the opportunity to continue UCB0942 treatment in this OLE study. The 
decision to enter this study must be made by the Investigator in consultation with the subject and 
his/her caregiver. The Investigator’s decision must take into account the benefit experienced and 
the potential risks of long-term exposure to UCB0942, as well as the potential benefit and risks 
of other treatment options available. It is expected that approximately 30 subjects will be 
enrolled. These subjects will be dosed with UCB0942 400mg bid or a tapered UCB0942 dose of 
200mg bid at the EV. 
A Data Monitoring Committee (DMC) will systematically monitor and report on the progress, 
safety, and/or critical efficacy endpoints of the study. This includes evaluating the safety signals 
and benefit-risk balance for the study subjects in relationship to new data relevant for the 
efficacy and safety of the investigational medicinal product (IMP). The benefit-risk balance of 
every subject entering the study will be reviewed by the DMC within 3 months after inclusion. 
The study consists of the following periods: 
• 2-week Screening Period from V13 to V15 (Days OP43 to OP57) of the 8-week Outpatient 
Maintenance Period of the EP0069 study. The Screening Visit will be on V13 of EP0069 and 
will be V1 of the current OLE study. 
• Evaluation Period of approximately 5 years, which will start with V2, the Entry Visit 
(EV), which is the same as V15 (Day OP57) of the 8-week Outpatient Maintenance Period of 
EP0069. 
• First year: In the first month of EP0073, subjects will have 2 telephone contacts (M1-Wk1 
[TC1] and M1-Wk3 [TC2]) and 1 clinic visit (M1-Wk2 [V3]). During the second, third and 
fourth months, subjects will visit the clinic at M2 (V4, minimal evaluation visit, MEV), M3 
(V5, full evaluation visit, FEV), and M4 (V6, MEV).  Subjects will return to the clinic every 
3 months for the remainder of the first year with FEV alternating with MEV: M7 (V7, FEV) 
and M10 (V8, MEV). 
• Second and third year: The subjects will have clinic visits every 3 months, with MEVs 
alternating with FEVs/Year evaluation visit, YEVs, beginning with M13 (V9, YEV). 
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• Fourth and fifth year: The subjects will have a clinic visit every 6 months with YEVs 
alternating FEVs. 
• Taper Period starting at the LEPV of the Evaluation Period; during the Taper Period, 
subjects will start to gradually decrease their dose of UCB0942. 
• SFU Period:  subjects must return to the clinic 1 week after administration of the final dose 
of UCB0942 (SFU1). A final visit (FV) will be scheduled 30 days after administration of the 
final dose of UCB0942 (SFU2). 
The study visits by month are shown in Table 2-1 (see the schedule of study assessments in 
Protocol’s Table 5-2). 
Table 2-1: 
Study visit schedule 
Month 
Visit 
Type of visit 
First study year 
M0 
V1 (V13 of EP0069) 
Screening Visit 
M1 
V2 (V15 of EP0069) 
EV 
M1-Wk1 
TC1 
TC 
M1-Wk2 
V3 
MEV 
M1-Wk3 
TC2 
TC 
M1-Wk4 
-a 
- 
M2 
V4 
MEV 
M3 
V5 
FEV 
M4 
V6 
MEV 
M5 
- 
- 
M6 
- 
- 
M7 
V7 
FEV 
M8 
- 
- 
M9 
- 
- 
M10 
V8 
MEV 
M11 
- 
- 
M12 
- 
- 
Second study year 
M13 
V9 
YEV 
M16 
V10 
MEV 
M19 
V11 
FEV 
M22 
V12 
MEV 
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Table 2-1: 
Study visit schedule 
Month 
Visit 
Type of visit 
Third study year 
M25 
V13 
YEV 
M28 
V14 
MEV 
M31 
V15 
FEV 
M34 
V16 
MEV 
Fourth study year 
M37 
V17 
YEV 
M43 
V18 
FEV 
Fifth study year 
M49 
V19 
YEV 
M55 
V20 
FEV 
M58 
V21 
YEV and LEVP/EDV 
Taper and SFU Periodsb 
Taper Period 
V22 
End of Taper Visit 
SFU1 
V23 
SFU at 1 week after last dose 
SFU2 
V24 
SFU at 30 days after last dose (FV) 
EDV=Early Discontinuation Visit; EV=Entry Visit; FEV=Full Evaluation Visit; FV=Final Visit; LEPV=Last 
Evaluation Period Visit; M=month; MEV=Minimal Evaluation Visit; SFU=Safety Follow-up; TC=Telephone Call; 
V=Visit; YEV=Yearly Evaluation Visit 
a The "-" denotes that no visit is scheduled in that month 
b Taper and SFU Periods to start with EDV or LEPV. 
2.4 
Determination of sample size 
For this OLE study, no sample size calculation is needed. The sample size will depend upon 
recruitment into and completion of the previous study. It is estimated that about 30 subjects 
(75%) from EP0069 will enter this EP0073 study. 
3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical evaluation will be performed by UCB or designee. Data may be summarized by study 
year, month, visit, and by timepoint, if applicable.  
The analysis datasets will follow the UCB analysis dataset model data specifications. 
All analysis will be performed using SAS® version 9.3, or higher (SAS Institute, Cary, NC, 
USA).  
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For continuous variables, summary statistics will include number of observations (n), mean, 
median, standard deviation (SD), minimum, and maximum, and may also include 25% and 75% 
quartiles. Categorical endpoints will be summarized using number of subjects, frequency, and 
percentages. Missing data will not be imputed apart from the exceptions as outlined in Section 
4.2. 
When reporting relative frequencies or other percentage values, the following rules apply: 
For values where all subjects fulfill certain criteria, the percentage value will be displayed as 
100. 
For values where the absolute frequency is 0, there will be no percentage presented at all. 
All other percentage displays will use 1 decimal place.  
When reporting descriptive statistics, the following rules will apply in general: 
• n will be an integer. 
• Mean, SD, and median will use 1 decimal place more than the original data. 
• Minimum and maximum will be reported using the same number of decimal places as the 
original value. 
Data collected at scheduled visits will be included in the by-visit summary. Data collected at 
unscheduled visits will not be included in the by-visit summary, but will be considered when 
determining the Last Value (Section 3.2.1.4), minimum, and maximum post-Baseline values. 
Details of statistical summaries for safety are described in Section 10. 
General statistical and reporting conventions are outlined in UCB Global Statistical Conventions; 
Version 1.1 dated 27 March 2014. 
3.2 
General study level definitions 
3.2.1 
Analysis periods 
Unless noted otherwise, Baseline is the EP0069 2-week Prospective Outpatient Baseline Period. 
In this study, final contact date is referred to date of final contact with subject from Study 
Completion eCRF form.  
The study is divided into 4 periods: Screening Period, Evaluation Period, Taper Period, and SFU 
Period. The following periods will be considered in the definition of efficacy and safety 
variables: 
• A 2-week Screening Period from V13 to the day before V15 of the 8-week Outpatient 
Maintenance Period of the EP0069 study. 
• Evaluation Period:  Entry Visit (EV) to Last Evaluation Period Visit (LEPV) or Early 
Discontinuation Visit (EDV) or clinical data cutoff date if the subject is ongoing and does not 
have the EDV. The EV is also V15 of EP0069. Data in EP0073 database will be used in the 
analyses when possible. If a subject does not have a Visit 21/EDV, then the date of the final 
contact will be defined as the end date of the Evaluation Period.  
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• Taper Period: the day after the end date of evaluation period to End of Taper Visit or clinical 
data cutoff date if the subject is ongoing. If the end of taper period (V22) is missing, here it is 
the algorithm to impute it: 
If EDV visit is missing then last date of evaluation period will be last contact date and taper and 
SFU period start/end dates will be missing. 
Else if the last dose date is before EDV date, then we assume drug was not tapered and taper 
period start/end date will be set as missing and SFU Period start date will be EDV+1 and SFU 
Period end date will be final contact date. 
Else if V22 is missing but SFU1 visit (V23) is not missing, then the end date of taper period be 
defined as max(last dose date, V23-7 days), but if this date is before the taper period start date, 
then taper period start/end dates will be set as missing. 
Else if V23 is missing but SFU2 (V24) is not missing, the end date of taper period as min(last 
dose date, V24-30 days). 
Else taper and SFU period start/end dates will be missing. 
• SFU Period: The day after the End of Taper Visit to date of final contact or clinical data 
cutoff date if the subject is ongoing.  
In addition, the On-Treatment Period is defined as from the date of first dose to the date of last 
dose of UCB0942 in EP0073 (Section 3.2.2).  
At the time of a clinical cutoff prior to the study completion, a subject will be classified as 
“discontinued” if the Study Completion CRF is available and the date of premature study 
termination is provided. All other subjects will be classified as “ongoing.” Only the data on or 
prior to the clinical cutoff date will be included in the analyses.   
3.2.2 
First and last dose of UCB0942 
Throughout this SAP, and unless otherwise stated, the first dose (of UCB0942) refers to the first 
UCB0942 administration in the EP0073 study reported on First Administration of Study 
Medication case report form (CRF). The last dose (of UCB0942) refers to the date of last 
administration of study medication reported on Study Completion CRF, at any EP0073 study 
period, Evaluation or Taper Period. 
At the time of a clinical cutoff, for subjects who are ongoing and not in the SFU Period, the last 
dose of UCB0942 will be set to the date of the clinical cutoff for the interim analyses. For 
subjects who are ongoing and in the SFU Period (ie, had the End of Taper Visit) at the time of a 
clinical cutoff, the last dose of UCB0942 will be set to the last dosing date on the Drug Dosing 
Log CRF for the interim analyses.  
3.2.3 
Relative day  
The relative day of an event will be derived with the start date of first UCB0942 administration 
in EP0073 as reference date, up to and including the last day of UCB0942 administration. 
Relative days for an event or measurement occurring before the reference date will have a 
‘-’ prefix and will be calculated as follows: 
Relative Day=−[(Event Date-Reference Date)] 
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Relative days for an event or measurement occurring on or after the reference date to the 
last day of UCB0942 administration are calculated as follows: 
Relative Day=[(Event Date-Reference Date)+1] 
For events or measurements occurring after the date of last dosing (as defined above), the 
relative day will be calculated with the date of last UCB0942 administration as reference date. 
Relative day in this case will be prefixed with ‘+’ in the data listings and will be calculated as 
follows: 
Relative Day=+[(Event Date-Reference Date)] 
There is no relative Day 0. Relative day is not calculated for partial dates in cases where relative 
day is shown in a subject data listing. In such cases, relative day should be presented as ‘--’ in 
the subject data listings. 
3.2.4 
Monthly time intervals  
A month is defined as 30 days and time intervals based on monthly durations are defined as a 
multiple of 30 days (eg, 12 months is defined as 360 days).  
Interval Duration Definition: 
- 
Months 0-3: Days 1-90 
- 
Months >3-6: Days 91-180 
- 
Months >6-9: Days 181-270 
- 
Months >9-12: Days 271-360 
Subsequent 3-month intervals are defined in a similar manner.  
For the analysis of efficacy variables during the Evaluation Period, 3-month intervals will be 
derived for the Evaluation Period. For the analysis of AEs and safety variables, 3-month intervals 
will be derived for the On-Treatment Period.  
3.2.5 
Last Value during the On-Treatment Period  
Last Value for safety parameters (such as clinical laboratory parameters, vital signs, ECGs) is the 
last available result obtained prior to or on the date of last dose of UCB0942 in EP0073. All 
scheduled and unscheduled assessments within this time period will be considered. Last Value 
will be determined separately for each laboratory parameter for hematology, chemistry, 
urinalysis assessments. Similarly, the minimum and maximum values are defined as the 
minimum and maximum values prior to or on the date of last dose of UCB0942.  
3.2.6 
Completer Cohort 
Because the duration of the Evaluation Period varies among the subjects, each subject will be 
classified into one or more of the following completer cohorts based on the duration of the 
Evaluation Period: 
≥3 months   : ≥90 days 
≥6 months   : ≥180 days 
≥12 months : ≥360 days 
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≥18 months :  ≥540 days 
≥24 months :  ≥720 days 
≥36 months :  ≥1080 days 
≥48 months :  ≥1140 days 
≥60 months =  ≥1800 days 
The duration of the Evaluation Period is calculated as the date of the end of the Evaluation 
Period – EV +1. Selected efficacy variables will be analyzed by completer cohorts.   
3.2.7 
Mapping of data from early discontinuation visits 
If an EDV occurs at the day of a scheduled visit, in-clinic safety and PK assessments should 
correspond to that scheduled visit. Safety assessments at an EDV that occurs on a day between 
two scheduled visits will be assigned to the next scheduled visit. No mapping will be performed 
for the seizure and QOLIE-31-P data collected at the EDV.  
In the by-visit summary tables, only nominal (scheduled) visits (after mapping) where the 
assessment is scheduled will be included. Unscheduled visits will not be mapped to scheduled 
visits. In the subject listing, data will be presented under the actual visits, including EDV and 
unscheduled visits. 
3.3 
Definition of Baseline values 
Baseline will be based on the EP0069 Baseline. For assessments performed at scheduled and 
unscheduled visits, Baseline will generally be the last result obtained prior to the first 
randomized dose administration of the EP0069 study.  
Baseline for the evaluation of seizure outcomes will be the EP0069 2-week Prospective 
Outpatient Baseline Period and the scores will be calculated as described in Section 3.10. 
3.4 
Protocol deviations 
Important protocol deviations are deviations from the protocol which could potentially have a 
meaningful impact on the study conduct or on the primary efficacy outcome, secondary efficacy 
variables, or key safety data for an individual subject.  
The criteria for identifying important protocol deviations and the classification of important 
protocol deviations will be defined separately in the Specification of Important Protocol 
Deviations (IPD) document. To the extent feasible, rules for identifying protocol deviations will 
be defined without review of the data and without consideration of the frequency of occurrence 
of such deviations. Important protocol deviations will be reviewed as part of the ongoing data 
cleaning process at Data Evaluation Meetings (DEMs) prior to lock of the database. 
3.5 
Analysis sets 
3.5.1 
Enrolled Set 
The Enrolled Set (ES) will consist of all enrolled subjects who have signed the informed consent 
form (ICF). 
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3.5.2 
Safety Set 
The Safety Set (SS) will consist of all enrolled subjects who took at least 1 dose of UCB0942 in 
the EP0073 study. 
3.5.3 
Full Analysis Set 
The full analysis set (FAS) will consist of all enrolled subjects who took at least 1 dose of 
UCB0942 and completed at least 1 seizure diary during the Evaluation Period in EP0073. 
3.5.4 
Pharmacokinetic Per-Protocol Set 
The Pharmacokinetic Per-Protocol Set (PK-PPS) will consist of subjects in the FAS who 
received at least 1 dose of UCB0942 in the EP0073 study and had at least 1 PK sample, and do 
not have a major protocol deviation impacting the PK for all the PK samples. PK-PPS exclusion 
should be based on the individual PK samples. Only if all PK samples are excluded, the subject 
will be excluded from the PK-PPS. 
3.6 
Treatment assignment and treatment groups 
This is an uncontrolled study in which all subjects receive UCB0942 in doses that are optimally 
adjusted for each subject. Statistical summaries will present all subjects combined as a single 
treatment arm unless otherwise indicated. 
3.7 
Center pooling strategy 
Subjects with highly drug-resistant focal epilepsy will be enrolled in approximately 25 sites. The 
data from all centers will be pooled. The data summaries and statistical analyses will not be 
performed by center, unless otherwise is stated. 
3.8 
Coding dictionaries 
Adverse events and medical history will be coded according to Version 22.0 (or later) of the 
Medical Dictionary for Regulatory Activities (MedDRA®) that are available to UCB. 
Medications will be coded according to the Version Sep/2017 (or later) of the World Health 
Organization Drug Dictionary (WHODD).    
The medical procedures will not be coded. 
3.9 
Changes to protocol-defined analyses 
Not applicable. 
3.10 
Definition of study-specific derived variables 
3.10.1 
Seizure frequency related variables 
3.10.1.1 
Seizure frequency 
Initial Processing of Diary Data 
Each seizure code in the clinical database will be mapped to exactly 1 of the following codes 
based on the 1981 International League Against Epilepsy (ILAE) classification: I, IA (IA1, IA2, 
IA3, IA4), IB (IB1, IB2), IC (IC1, IC2, IC3), II, IIA (IIA1, IIA2), IIB, IIC, IID, IIE, IIF, or III.  
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With regard to cluster seizures, investigator sites are to report the number of cluster episodes 
rather than reporting the estimated number of individual seizures. Therefore, no imputation will 
be applied for the seizure counts corresponding to reports of cluster seizures. 
Observable focal-onset seizures include Type IA1, IB, and IC. Focal-onset seizures include all 
Type I seizures. To apply the terminology consistently, observable focal-onset seizures and all 
Type I seizures will be used when appropriate unless noted otherwise.  
Calculation of Total Seizure Counts by Analysis Period and Interval 
The total number of seizures for seizure types IA1, IB (i.e. IB1 and IB2), IC (i.e. IC1, IC2, and 
IC3), the total number of observable focal-onset seizures (IA1+IB+IC), the total number of all 
Type I seizures, and the total number of seizures for all seizure types (I+II+III) will be calculated 
across all diary records over a given analysis period or interval being summarized. 
Calculation of Adjusted Seizure Frequency 
Baseline seizure frequency will be obtained from the EP0069 2-week Prospective Outpatient 
Baseline Period. 
Twenty-eight day adjusted seizure frequency for seizure types IA1, IB (i.e. IB1 and IB2), IC (i.e. 
IC1, IC2, and IC3), the observable focal-onset seizures (IA1+IB+ IC), and all Type I seizures 
during the Evaluation Period will be calculated overall, within each 3-month time interval, and 
over each completer cohort interval by dividing the number of seizures for each seizure type by 
the number of days for which the diary was completed during a given analysis period or interval, 
and multiplying the resulting value by 28.  
3.10.1.2 
Percent reduction in seizure frequency 
Percent reduction from Baseline in seizure frequency to the corresponding interval will be 
calculated using the following formula: 
Reduction 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 28-day adjusted seizure frequency during the 
period of interest from the 28-day adjusted seizure frequency during the EP0069 2-week 
Prospective Outpatient Baseline period. 
3.10.1.3 
XX% Responder Rate in focal seizure frequency 
A subject is defined as a responder if s/he has a reduction in seizure frequency of at least XX% 
from their Baseline seizure frequency. The XX% RRs that will be calculated include, but are not 
limited to 50%, 75%, and will be calculated as follows:  
Count of XX% responders during the period
Number of subjects during the period
 × 100 
3.10.2 
Seizure freedom   
Subjects will be considered seizure free for a given period or time interval if the subject, 
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: 
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Count of seizure free subjects during the period
Number of subjects during the period
 × 100 
3.10.3 
Seizure-free days 
The number of seizure-free days is defined as the total number of days within an analysis period 
or time interval for which no seizures are reported. The percentage of seizure-free days is to be 
computed as 100 times the number of seizure-free 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) should not be used in these computations.  
3.10.4 
Patient Weighted Quality of Life in Epilepsy Inventory 
The Patient Weighted QOLIE-31-P is an adaptation of the original QOLIE-31 (Cramer et al, 
1998). The QOLIE-31-P includes 30 items grouped into 7 multi-item subscales (seizure worry [5 
items], overall quality of life [2 items], emotional well-being [5 items], energy/fatigue [4 items], 
cognitive functioning [6 items], medication effects [3 items], and social function [5 items]) and a 
health status item. The QOLIE-31-P total score, subscale scores, and health status item score are 
calculated according to the scoring algorithm described below, with scores ranging from 0 to 100 
and higher scores indicating better functioning. In addition to these 31 items, the QOLIE-31-P 
includes 7 items assessing the degree of “distress” associated with the topic of each subscale (ie, 
distress items) and 1 item asking about the relative importance of each subscale topic (ie, 
prioritization item).  
Subscale Scores 
As a first step to calculating the subscale scores, the individual responses for the 30 subscale 
items are rescaled to a 0 to 100 scale with higher scores reflecting better functioning; the rescaled 
values for each item are defined in the scoring manual. Each subscale score is then calculated by 
summing the rescaled responses for that subscale and dividing by the number of items with a 
non-missing response. A subscale score will be calculated only if at least 50% of the items 
within the subscale are present. 
Total Score 
Total score is calculated as a weighted sum of the subscale scores based on the weighting in the 
scoring manual. Total score will be missing if at least 1 subscale score is missing. Total score 
will range from 0 to 100 with a higher score reflecting better functioning.  
Health Status Item 
Responses for the health status item are a multiple of 10 ranging from 0 to 100 with a higher 
score corresponding to a better health status. The health status item response is analyzed without 
rescaling. 
Distress Items 
Each subscale includes 1 distress item. The response for each distress item is an integer ranging 
from 1 to 5. The response for each distress item will be converted to a 0 to 100 scale (ie, 0, 25, 
50, 75, and 100) with a higher score corresponding to greater distress. 
Prioritization Item 
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The response for each subscale for the prioritization item is an integer ranging from 1 to 7. The 
prioritization ranking is analyzed without rescaling. 
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
No statistical testing is planned; therefore, this section is not applicable. 
4.2 
Handling of dropouts or missing data 
4.2.1 
Seizure diary 
Seizure frequency (subjects with POS) will be calculated over non missing diary days during 
each study period or time interval as described in Section 3.10; diary days for which seizure data 
were not recorded (ie, “Not Done” is ticked) will not be considered in the calculation of seizure 
frequency or seizure days.  
If seizures are reported on a day, but the ILAE seizure code is unknown, the day will be excluded 
from the seizure frequency calculation for all seizure types. If seizures are reported on a day, the 
ILAE seizure code is known but the number of seizures is unknown, the day will be excluded 
from the seizure frequency calculation for the applicable seizure type. As long as seizures are 
reported on a day, the day will be counted as one day with seizure in the seizure free-days and 
seizure freedom calculations.  
4.2.2 
QOLIE-31-P 
The QOLIE-31-P score will be summarised without any imputations, and also, only for Month 
13 (V9, YEV), using the post-baseline last observation carried forward (LOCF) imputation 
method. For each individual, missing values for the QOLIE-31-P score will be replaced by the 
post-baseline last observed postbaseline value of that variable. 
4.2.3 
Partial/Missing Data for adverse events and concomitant medications: 
For analyses of AEs and concomitant medication usage, a complete date must be established to correctly 
identify the AE or medication as occurring during treatment or not. In the event of completely missing 
dates, or if ambiguity or incomplete data makes it impossible to determine whether a medication was 
concomitant, or an adverse event was treatment emergent, the medication will be considered as 
concomitant or the adverse event will be considered treatment emergent.  
For purposes of imputing missing components of partially-reported start and stop dates for AEs and for 
medication use, the algorithms listed below will be followed. Start and stop dates of AEs or concomitant 
medication will be displayed as reported in the subject data listings (i.e., no imputed values will be 
displayed in data listings).  
Partial AE and concomitant medication start dates will be imputed as described in the following sections. 
Imputation of Partial Start Dates  
• 
If only the month and year are specified and the month and year of first dose of UCB0942 is not the 
same as the month and year of the start date, then use the 1st of the month 
• 
If only the month and year are specified and the month and year of first dose of UCB0942 P is the 
same as the month and year of the start date, then use the date of first dose of UCB0942 
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• 
If only the year is specified, and the year of first dose of UCB0942 is not the same as the year of the 
start date, then use the 1st of January of the year of the start date 
• 
If only the year is specified, and the year of first dose of UCB0942 is the same as the year of the start 
date, then use the date of first dose 
• 
If the start date is completely unknown and the stop date is unknown or not prior to the date of first 
dose of IMP, then use the date of first dose of UCB0942. 
• 
If the imputed start date is after the known stop date, set the start date to be the same as the stop date.  
Imputation of Partial Stop Dates 
• 
If only the month and year are specified, then use the last day of the month 
• 
If only the year is specified, then use December 31st of that year 
• 
If the stop date is completely unknown, do not impute the stop date 
4.3 
Interim analyses and data monitoring 
A DMC will systematically monitor and report (at least quarterly up to the timepoint when the 
last patient entering EP0073 reaches 1 year in the study, and less frequent thereafter) on the 
progress, safety, and/or critical efficacy endpoints of this study by convening to review the 
ongoing program safety and efficacy data. This includes evaluating the safety signals and 
benefit-risk balance for the study subjects in relationship to new data relevant for UCB0942 
efficacy and safety. The benefit-risk balance of every subject entering the study will be reviewed 
by the DMC within 3 months after inclusion. Blinded data until database lock from EP0069 and 
data from the OLE EP0073 studies will be reviewed in order for the DMC to provide an ongoing 
benefit-risk evaluation with particular reference to the occurrence of psychiatric and 
cardiological/ cardiovascular AEs, seizure control, and any new identified safety signals. Voting 
members of the DMC will include external physicians with experience in treating refractory 
epilepsy and a cardiologist, none of whom will be involved with the conduct of the study, either 
by management or participation. In addition, there will be an independent reporting team, 
consisting of an independent statistician and independent statistical programmers, who will be 
completely independent from the blinded reporting team. The blinded reporting team will be 
responsible for all operational aspects of the study, including routine monitoring and cleaning of 
the data, programming, and quality control of all analyses defined in the EP0073 DMC SAP, on 
blinded data of EP0069, and unblinded data of EP0073 (as an open-label study). If required for 
monitoring of safety and benefit-risk of EP0073 patients, unblinded data from EP0069 can be 
reviewed by the external members of the DMC at closed sessions and provided by an 
independent statistician. The DMC will make recommendations to the company, which may 
include changes to study procedures, withdrawal of subjects with a negative risk balance, or 
termination of the clinical study. 
A DMC Charter will define the composition, roles, and responsibilities of the DMC, specify the 
data to be reviewed and the periodicity of data review, and determine the procedures to be 
followed to maximize subject safety and ensure positive benefit-risk balance of participation in 
the study.  
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Interim analyses may be produced while this study is ongoing to support annual reports, 
regulatory submissions, and publications. There are no statistical concerns with such interim 
assessments for this study design.  
4.4 
Multicenter studies 
Data from different centers will be pooled.  
4.5 
Multiple comparisons/multiplicity 
No statistical testing is planned; therefore, this section is not applicable. 
4.6 
Use of an efficacy subset of subjects 
All efficacy analyses will be performed on the FAS. No further efficacy subsets are defined for 
this study. 
4.7 
Active-control studies intended to show equivalence 
Not applicable. 
4.8 
Examination of subgroups 
Because of small number of subjects, no subgroup analyses will be performed.  
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Subject disposition 
The number of subjects screened, enrolled into the study, and subjects included in each analysis 
set will be summarized using ES. Subjects who completed or prematurely discontinued the 
study, as well as the reason for discontinuation, will be presented for the SS. The 
discontinuations due to AEs will be summarized in a separate table for the SS.  
The number of subjects who are ongoing at the time of the clinical cutoff will be mentioned for 
any interim analysis.  
In addition, the following listings will be provided for the ES: 
• Subject disposition  
• Study discontinuation  
• Subject visit dates  
• Subject analysis sets  
5.2 
Protocol deviations 
A listing of all important protocol deviations identified at the database pre-lock meeting will be 
presented for all subjects in the SS and will include the deviation type (inclusion criteria, 
exclusion criteria, withdrawal criteria, prohibited concomitant medication use, incorrect 
treatment or dose, treatment non-compliance, procedural non-compliance), and description.  
The number and percentage of subjects in the SS with important protocol deviations will be 
summarized overall and by category of protocol deviation. The denominator for percentages will 
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be the number of subjects in the SS. Protocol deviations will only be summarized for the final 
analysis. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
6.1 
Demographics 
A by-subject listing of demographic characteristics at the time of entry into the EP0073 study 
will be presented for the ES. This will include the date of birth, age (in years), sex, race, 
ethnicity, height (in cm), weight (in kg), and body mass index (BMI, in kg/m²).  
Baseline demographic characteristics obtained at the Entry Visit (apart from the date of birth) 
will be summarized for the SS for all subjects.  
BMI (in kg/m²) is calculated based on the following formula: 
BMI (kg
m2) = Weight (kg) 
Height (m)2 
Body mass index will be reported to 1 decimal place. 
The following age groups will be summarized in the same table: 
− 12 - <18 years 
−  ≤18 years 
− 18 - <65 years 
− 19 - <65 years 
− 65 - <85 years 
− ≥65 years 
− ≥ 85 years 
 
Childbearing potential will be listed in a separate listing.  
6.2 
Medical history and concomitant diseases 
Medical history and ongoing medical conditions for EP0073 will be listed and summarized for 
the SS and MedDRA® system organ class (SOC) and preferred term (PT). The start date (month 
and year only) and end date (or ongoing if applicable) will also be included in the listing. 
Epilepsy history will not be included in these tables. 
The summary of medical history will be based on the medical history at the time of entry into 
EP0069 and any updates at EV. 
Concomitant medical procedures carried out during the study will be listed for the SS. 
6.2.1 
History of epilepsy 
All of the following are summarized using data collected at the time of entry into the EP0069 
study. The history of epilepsy will be listed and summarized for all subjects in the SS.  
Epileptic seizure profile 
The number and percentage of subjects experiencing each seizure type at any time prior to the 
study entry will be summarized for the SS based on the ILAE Seizure Classification History 
EP0069 eCRF (historical seizures count). 
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The overall number and percentage of subjects with a history of type I seizures and the overall 
number and percentage of subjects with a history of type II seizures will also be summarized. A 
subject will be classified as having a history of type I seizures if the subject has a history of IA, 
IA1, IA2, IA3, IA4, IB, IB1, IB2, or IC seizures. A subject will be classified as having a history 
of type II seizures if the subject has a history of IIA, IIB, IIC, IID, IIE, or IIF seizures. 
History of epileptic seizures 
History of epileptic seizures, including the number and percentage of subjects with a history of 
status epilepticus, the number and percentage of subjects with a history of withdrawal seizures, 
and quantitative summaries of epilepsy duration relative to the Entry Visit of EP0073 (ie, Entry 
Visit of EP0073 minus the date of the first epileptic seizure plus 1 divided by 365.25), age at 
onset of first seizure relative to the Entry Visit of EP0073, and percent of life with epilepsy 
relative to the Entry Visit of EP0073, will be summarized for the SS. 
6.3 
Other Baseline Characteristics 
The following data collected at the time of entry into the EP0069 study will be summarized for 
the SS. The parameters derived in EP0069 will be directly used.  
Number of past AEDs  
The number of past AEDs taken prior to EP0069 will be summarized for the SS based on the 
following categorization: <4, 4 or 5, 6 or 7, 8 to 10, >10 AEDs.  
Number of prior AEDs 
The number of AEDs taken prior to EP0069 will be summarized for the SS based on the 
following categorization: <4, 4 or 5, 6 or 7, 8 to 10, >10 AEDs.  
Use of vagus nerve stimulation  
The number and percentage of subjects with active vagus nerve stimulation (VNS), and the 
number and percentage of subjects with no VNS implant or a non-active VNS implant prior to 
EP0069 will be summarized for the SS. 
Number of AEDs taken at EP0069 study entry 
The number and percentage of subjects taking 1, 2, and ≥3 AEDs at the time of EP0069 study 
entry will be summarized for the SS. 
Levetiracetam use at EP0069 study entry 
The number and percentage of subjects in each LEV-use category at EP0069 study entry will be 
summarized for the SS: 
LEV prior and current use (concomitant use of LEV at study entry). 
LEV Prior Use Only=History of prior LEV use and must have discontinued 4 weeks prior to 
study entry. 
LEV Naïve=No history of prior LEV use, and no use at study entry. 
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6.4 
Concomitant medications 
The medications will be classified as AEDs or non-AEDs. For interim analyses, any non-coded 
terms will report the levels as UNCODED in the listing and table.  
Medications will be considered as concomitant if 
− the start date of the medication is on or after the date of first dose of UCB0942 in EP0073 
and the start date is not after the date of last dose in EP0073 
− Or the start date is prior to the first dose of UCB0942 in EP0073 but the stop date is after 
the first dose in EP0073 or ongoing.  
6.4.1 
Non- Antiepileptic drugs 
All concomitant non-AED medications will be listed for the SS by WHODD Anatomical Main 
Group [Level 1], Therapeutic Subgroup [Level 2], PT and reported term.  
The number and percentage of subjects taking concomitant non-AED medications during 
EP0073will be summarized separately for the SS by WHODD Anatomical Main Group 
[Level 1], Therapeutic Subgroup [Level 2], and PT for the whole study period.  
6.4.2 
Concomitant AEDs 
Concomitant AED medications will be listed separately for the SS by WHODD Therapeutic 
Subgroup [Level 2], Chemical [Level 4], PT and reported term.  
The number and percentage of subjects taking concomitant AED medications will be 
summarized by chemical/therapeutic/pharmacological subgroup (ATC classification level 4), and 
preferred drug name for the SS. 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
Information reported on the CRF regarding tablets/bottles dispensed and returned will be 
reported in subject data listings. Treatment compliance will be evaluated through the review of 
important protocol deviations. 
8 
EFFICACY ANALYSES 
All seizure diary data will be listed and analyzed on the FAS. The summaries will include the 
statistics for continuous or categorical variables as specified in Section 3.1. 
The derivations of 28-day adjusted seizure frequency are described in detail in Section 3.10.1. 
All summaries of efficacy data are descriptive. No statistical testing will be performed. 
8.1 
Statistical analysis of the primary efficacy variable 
A 75% responder is defined as a subject with a ≥75% reduction in observable focal-onset seizure 
(Type IA1, IB, and IC) frequency relative to the EP0069 2-week Prospective Outpatient Baseline 
Period. Seizure frequency will be standardized to a 28-day duration.  
The primary efficacy variable is the 75%RR and will be summarized by 3-month intervals over 
the Evaluation Period and by complete cohort using descriptive statistics.  
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8.1.1 
Supportive analysis  
The 75% RR will be calculated using all Type I seizures and will be summarized by 3-month 
intervals over the Evaluation Period using descriptive statistics. 
The primary analysis described in Section 8.1 will be repeated for the 75% RR, calculated using 
all Type I seizures.  
8.2 
Statistical analysis of the secondary efficacy variables 
8.2.1 
Observable focal-onset seizure frequency  
Twenty-eight day adjusted observable focal-onset seizure frequency (Type IA1+IB+IC) will be 
summarized with quantitative descriptive statistics for all subjects for the EP0069 2-week 
Prospective Outpatient Baseline Period by 3-month time intervals and by completer cohort over 
the Evaluation Period.  
8.2.2 
Focal-onset seizure frequency by seizure type 
The summaries described in Section 8.2.1  will be repeated for all Type I seizures and by seizure 
types IA1, IB, IC. 
8.2.3 
Percent reduction in focal-onset seizure frequency 
The percent reduction in observable focal-onset seizure (Type IA1+IB+IC) and All Type I 
seizure frequency from the 2-week Prospective Outpatient Baseline Period to 3-month time 
intervals over the Evaluation Period will be computed as defined in Section 3.10.1.  
Percent reduction from the 2-week Prospective Outpatient Baseline for observable focal-onset 
seizure and All Type I seizure frequency will be summarized using quantitative descriptive 
statistics by 3-month time intervals and by completer cohort over the Evaluation Period.  
8.2.4 
50%RR on percent reduction in 28-day observable focal-onset seizure 
frequency  
A 50% responder is defined as a subject with a ≥50% reduction in observable focal-onset seizure 
and all Type I seizure frequency relative to the EP0069 2-week Prospective Outpatient Baseline 
Period. Seizure frequency will be standardized to a 28-day duration.  
The 50% responder rate (50%RR) will be calculated for 3-month time intervals over the 
Evaluation Period and by completer cohort and will be summarized using descriptive statistics.  
8.2.5 
Percentage of seizure free days 
The percentage of seizure free days will be listed and tabulated by 3-month intervals over the 
Evaluation Period and by complete cohort in frequency tables.  
8.2.6 
Seizure freedom 
The seizure freedom rate will be calculated and summarized over the Evaluation Period and by 
completer cohort.  
8.2.7 
Quality of Life 
The observed value and the change from Baseline for the QOLIE-31-P total score and its 
sub-scores (Seizure Worry, Daily Activities/Social Function, Energy/Fatigue, Emotional 
Well-Being, Cognitive Function, Medication Effects, Overall Quality of Life, and Health Status) 
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will be summarized for all available visits (Month 3, 7, 13, 19, 25, 31, 37, 43, 49, 55 and 58) for 
the FAS. Only subjects with a non-missing change from the EP0069 Baseline will be 
summarized at each timepoint. 
The observed ranks for the prioritization items (Seizure Worry, Daily Activities/Social Function, 
Energy/Fatigue, Emotional Well-Being, Cognitive Function, Medication Effects, and Overall 
Quality of Life) will be summarized at all available timepoints as above and for all subjects and 
by study visit cohort as defined above in separate tables. Changes from Baseline will not be 
summarized, and only the numbers of subjects and sample means will be presented. 
The QOLIE-31-P mean change from Baseline for the total score and the sub-scores will be 
plotted in line plots with 95% CIs (assuming normally distributed data) for the whole study 
period. 
The observed value and the change from Baseline for the post-baseline LOCF imputed values for 
the QOLIE-31-P total score and its sub-scores at Month 13 (V9, YEV) will be summarized for 
the FAS.  
8.2.8 
Time to discontinuation 
Kaplan-Meier estimates of the percentage of subjects completing 3, 6, 12, 18, 24, 36, 48, and 60 
months of treatment will be provided. The corresponding Kaplan-Meier plot will also be 
provided. For subjects who discontinued from the study, the event date is set to the date of last 
dose of UCB0942 and the time to event will be calculated as the date of last dose minus the date 
of first dose of UCB0942 in EP0073 plus 1. Subjects who completed the study will be censored 
as of the date of last dose of UCB0942. At a clinical cutoff, subjects who are ongoing will be 
censored as of the date of last dose of UCB0942 defined for the interim analyses (Section 3.2.2). 
9 
PHARMACOKINETICS  
This data may be used for any refinement of the UCB0942 population PK modeling. The 
population PK analysis is outside the scope of this SAP.   
Individual PK data will be reported for the FAS and the analyses will be reported for the 
PK-PPS.  
9.1 
Plasma concentrations 
Plasma concentrations of UCB0942, 
, and 
will be 
determined from blood samples obtained in the study during the first year (V3, V4, V5, V6, V7, 
V8, V9).  
The individual concentrations of UCB0942, 
, and 
 will be 
listed for the FAS with blood sampling dates/times and elapsed time from last administration. 
Unless otherwise stated, measured values below the limit of quantification (BLQ) will be 
reported as LLOQ/2. 
9.2 
Population pharmacokinetics 
If appropriate, a population PK analysis of UCB0942 and identified active metabolites, may be 
performed using non-linear mixed effects modeling within the population software (NONMEM) 
aimed at identifying relevant covariates (demographic variables, other AEDs). An evaluation of 
longer term (up to 1 year) exposure-response relationships to support the understanding of the 
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clinical efficacy profile of UCB0942 may be undertaken. These population analyses will be 
performed by UCB and will be described in a separate data analysis plan (DAP), and it will be 
reported in a separate report. 
10 
SAFETY ANALYSES 
Safety is assessed with AEs, laboratory tests (blood chemistry, hematology, urinalysis, and 
pregnancy test), vital signs, body weight, ECGs, physical examination, psychiatric assessment 
using the BPRS, cognition/memory assessment using the MMSE, withdrawal symptoms using 
CIWA-B, echocardiography and neurological examination. Summary tables will be provided for 
AEs; blood chemistry, hematology, urinalysis, and vital signs, body weight, ECGs, and 
echocardiography. No summary tables will be provided for pregnancy testing, physical 
examination, and neurological examination. 
All safety summaries will be based on the SS. 
10.1 
Extent of exposure 
All UCB0942 administration information will be listed by subject.  
A daily dose will be calculated for each study day from the day of first dose of UCB0942 to the 
day of last dose of UCB0942 for the purposes of calculating modal dose. Daily dose will be 
calculated as the sum of the AM and PM dose for each day. 
Modal daily doses will be calculated across all study days on or after the day of first dose of 
UCB0942 and up to and including the day of last dose of UCB0942. Modal daily dose is the 
most frequently taken daily dose during this period. In the event of a tie, the modal dose will be 
set to the lower of the tied doses. Modal daily dose will be categorized as ≤200mg/day, 
>200mg/day to ≤400mg/day, >400mg/day to ≤600mg/day, >600mg/day to ≤800mg/day, and 
>800mg/day.  
For subjects who completed or discontinued from the study, the overall duration of exposure will 
be calculated as the date of last dose of UCB0942 minus the date of first dose of UCB0942 in 
EP0073 plus 1 day. For ongoing subjects at a clinical cutoff, the duration of exposure will be 
calculated based on the date of last dose of UCB0942 defined for the interim analyses (Section 
3.2.2). Subject years of exposure will be calculated by summing the exposure duration in days 
for all subjects being summarized and dividing the resulting value by 365.25. 
The number and percentage of subjects exposed to UCB0942 will be summarized overall and by 
modal dose category. The number and percentage of subjects exposed for ≥3, ≥6, ≥12, ≥18, ≥24, 
≥36, ≥48, and ≥60 months will be summarized. 
10.2 
Adverse events 
Adverse events that occurred up to the first EP0073 UCB0942 administration will be recorded in 
the EP0069 database. Adverse events that occurred from the first EP0073 UCB0942 
administration until study completion or study termination will be captured in the EP0073 
database. All AEs will be coded using the latest available version of MedDRA and will be 
categorized by intensity (mild/moderate/severe). 
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10.2.1 
Definition of treatment-emergent AE 
A treatment-emergent adverse event (TEAE) is defined as 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.  
Where dates are missing or partially missing, AEs will be assumed to be treatment-emergent, 
unless there is clear evidence (through comparison of partial dates, see Section 4.2) to suggest 
that the AE started prior to the first dose of study treatment. AEs with an incomplete onset date 
will be classified as TEAEs if the month and year of onset (when only the month and year are 
specified) is the same as the month and year of the first UCB0942 dose or the year of onset 
(when only year is specified) is the same as the year of first UCB0942 dose. TEAEs are assigned 
into an analysis period or time interval based on the onset date. 
10.2.2 
General summaries of TEAEs 
Listings will be provided for all AEs, SAEs, AEs leading to discontinuation (ie, drop out), and 
AEs leading to death by subject for the SS. 
Unless noted otherwise, TEAEs during the study (including the Taper and SFU Periods) will be 
summarized. At the time of a clinical cutoff, TEAEs with onset date prior to or on the clinical 
cutoff date will be summarized.  
The following tabular summaries will be presented for the SS: 
• Ongoing AEs at EP0073 study entry. Of note, this table will not be included in the interim 
analyses. 
• Incidence of TEAEs during the Study - Overview  
• Incidence of TEAEs by 3-month time interval during the On-Treatment Period. TEAEs with 
onset date prior to or on the date of last dose of UCB0942 will be included in the summary.  
• Incidence of TEAEs by Period (Entire Study, Evaluation, Taper, SFU) 
• Incidence of Serious TEAEs  
• Incidence of TEAEs by Relationship 
• Incidence of SAEs by Relationship. Of note, this table is needed for data transparency 
reporting and will not be included in the interim analyses. 
• Incidence of Fatal TEAEs by Relationship. Of note, this table is needed for data transparency 
reporting and will not be included in the interim analyses. 
• Incidence of TEAEs by Maximum Intensity 
• Incidence of TEAEs leading to discontinuation (ie, drop out)   
• Incidence of TEAEs occurring in at least 5% of Subjects  
• Incidence of TEAEs by Dose at Onset during the On-Treatment Period. TEAEs with onset 
date prior to or on the date of last dose of UCB0942 will be included in the summary.  
• Incidence of Non-Serious TEAEs above the Threshold of 5% of Subjects. Of note, this table 
is needed for data transparency reporting and will not be included in the interim analyses.   
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Summary tables will contain counts of subjects, percentages of subjects in parentheses and the 
number of events where applicable. A subject who has multiple events in the same SOC and PT 
will be counted only once in the subject counts but all events will be included. 
In summaries of relationship to study treatment per the investigator, the following relationships 
will be summarized: ‘Not related’, ‘Related’. Events with missing relationship will be considered 
as ‘Related’ to the last given study product for summary purposes but recorded as missing in the 
listings. 
In summaries of maximum intensity, the following intensity categories will be summarized: 
‘Mild’, ‘Moderate’, ‘Severe’. Subjects who experience the same event multiple times will be 
included in the most severe category. Events with missing intensity will be considered as 
‘Severe’ events for summary purposes but recorded as missing in the listings. 
Adverse event summaries will be ordered in alphabetically by SOC and by decreasing frequency 
for the PT within SOC. 
10.3 
Clinical laboratory evaluations 
Clinical laboratory parameters (clinical chemistry, hematology, urinalysis) are assessed at all 
FEVs, YEVs, EDVs, and at FV and may also be assessed at Unscheduled Visits.  
All summaries of laboratory parameters will only summarize parameters planned based on the 
protocol; however, both planned and unplanned laboratory parameters will be provided in 
subject data listings. 
Observed laboratory data (chemistry, hematology, urinalysis measurements as listed in Table 10-
1), and changes from the EP0069 Baseline for numeric parameters will be listed and summarized 
by visit, including Last Value, minimal, and maximum value.  Laboratory values will be grouped 
according to the laboratory function panel shown in Table 10-1) and flagged based on the 
possibly clinically significant treatment emergent (PCST) criteria (see Section 12.1), if 
applicable. Treatment-emergent values are those occurring any time after the first dose of 
UCB0942 in EP0073. The number and percentage of subjects with a PCST value will be 
summarized for the overall On-Treatment Period and by 3-month. Percentages will be relative to 
the number of subjects with an assessment during the interval. Subject numbers for those 
meeting the PCST will also be presented.   
Possibly clinically significant treatment emergent criteria are based on FDA Division of 
Neuropharmacologic Drug Products guidelines with some UCB-defined additions (Section 12.1).  
Additional laboratory tests performed will be listed, but will not be summarized.  
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Table Error! No text of specified style in document.‒1: Clinical laboratory measurements 
Category 
Panel 
Variable 
Hematology 
Red blood cell 
RBC count, hemoglobin, hematocrit, 
MCH, MCHC, MCV 
White blood cell 
WBC count, basophils, eosinophils, 
lymphocytes, monocytes, neutrophils 
Platelet 
Platelet count 
Clinical 
Chemistry 
Electrolytes 
Sodium, chloride, potassium 
Minerals 
Calcium, magnesium 
Metabolic 
Glucose 
Liver function 
ALP, ALT, AST, total bilirubin, LDH 
Kidney function 
BUN or urea, creatinine 
Urinalysis 
Dipstick 
Total protein, pH, glucose, WBC, RBC   
ALP=alkaline phosphatase, ALT=alanine aminotransferase, AST=aspartate aminotransferase, LDH=lactate 
dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin concentration; 
MCV=mean corpuscular volume; RBC=red blood cell; WBC=white blood cell. 
10.3.1 
Subjects with potential drug-induced liver injury (PDILI) 
There are specific criteria described in the protocol Section 11.6.1 to evaluate subjects for potential drug-
induced liver injury (PDILI). A summary of number and percent of subjects meeting PDILI criteria will 
be provided along with the subject numbers. Data collected for PDILI subjects will be listed.  
A summary table highlighting the potential cases of Hy’s Law will be presented. Potential cases of Hy’s 
Law is defined as:  
• 
AST >3xULN or ALT >3xULN and 
• 
Total Bilirubin >2xULN 
In order to meet the above criteria, a subject must experience the elevation in bilirubin and ALT or AST 
at the same visit. For example, a subject who experiences a >=2 x ULN elevation of bilirubin at one visit 
and a 3 x ULN elevation in ALT (or AST) at a subsequent visit has not fulfilled the Hy’s law criteria.  
10.4 
Vital signs, physical findings, and other observations related to 
safety 
10.4.1 
Vital signs 
Vital signs (including weight) are assessed at all FEVs, MEVs, YEVs, EDVs, and at FV, and 
may also be assessed at Unscheduled Visits.  
A by-subject listing of all observed vital measurements (including systolic blood pressure [SBP], 
diastolic blood pressure [DBP], pulse rate [PR], respiratory rate, weight) and changes from 
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EP0069 Baseline will be listed. This listing will include a flag for measurements identified as 
being abnormal  by the criteria outlined in Section 12.2.  
Measured values, and changes from Baseline for all vital sign measurements (excluding 
temperature) will be summarized by visit, including Last Value, maximum value, and minimal 
value.  
The number and percentage of subjects with abnormal vital signs will be summarized for the 
overall On-Treatment Period and by 3-month interval. Percentages will be relative to the number 
of subjects with an assessment during the interval. Subject numbers meeting the abnormal 
criteria will also be presented.  
10.4.2 
Electrocardiograms 
Observed ECG data (heart rate, PR, QT, QTcB [QT using Bazett’s], QTcF [QT using 
Fridericia’s formula], and QRS) and changes from EP0069 Baseline will be listed. The listing 
will include a flag for measurements identified as being abnormal by the criteria outlined in 
Section 12.3.  
Measured values, and changes from Baseline for all vital sign measurements will be summarized 
by visit, including Last Value, maximum value, and minimal value. The number and percentage 
of subjects with no abnormality, an abnormal but not clinically significant finding, and a 
clinically significant finding will be summarized by visit. Percentages will be relative to the 
number of subjects with an ECG result at each visit.  
The number and percentage of subjects with an abnormal ECG value will be summarized for the 
overall On-Treatment Period and by 3-months interval. Percentages will be relative to the 
number of subjects with an assessment during the interval. Subject numbers meeting the 
abnormal criteria will also be presented. 
ECG findings will be listed and summarized by visit.  
10.4.3 
Doppler echocardiography 
Doppler echocardiography results (including valvular and other cardiac abnormalities) will be 
listed and summarized by visit.  
10.4.4 
Physical examination 
A listing of abnormal physical examination findings will be provided; no summaries of physical 
examination findings are planned. 
10.4.5 
Columbia-Suicide Severity Rating Scale  
C-SSRS data will be provided in subject listing for subjects with suicidal ideation and suicide 
behavior. 
10.4.6 
Neurological examination 
A listing of abnormal neurological examination findings will be provided; no summaries of 
neurological examination findings are planned. 
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10.4.7 
Psychiatric and cognition assessment, and withdrawal monitoring  
Psychiatric and cognitive assessments (BPRS and MMSE throughout the study) observed results 
and changes from EP0069 Baseline will be listed. The changes from EP0069 Baseline in the total 
scores will be summarized. 
Any symptoms of withdrawal reactions will be monitored using the CIWA-B questionnaire. The 
CIWA-B scores will be listed and the total score will be summarized. 
10.4.8 
Employment and living status and epilepsy surgery status 
Employment and living status and epilepsy surgery status data at Visit 2 will be listed.  
 
 
 
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11 
REFERENCES 
Cramer JA, Perrine K, Devinsky O, Bryant-Comstock L, Meador K, Hermann B. Development and cross-
cultural translations of a 31-item quality of life in epilepsy inventory. Epilepsia. 1998:39(1):81-8. 
 
 
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12 
APPENDICES  
12.1 
PCST Criteria for Hematology, Serum Chemistry and Urinalysis Parameters 
12.1.1 
Hematology 
PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
Hematocrit 
<2y 
% 
≤27 
>45 
% 
≤27 
>45 
2y - <18y 
≤29 
>47 
≤29 
>47 
≥18y 
≤85% of LLN 
≥115% of ULN) 
≤85% of LLN 
≥115% of ULN 
Hemoglobin 
<2y 
g/dL 
≤9.0 
>15.0 
g/L 
≤90 
>150 
2y - <18y 
≤9.5 
>16.0 
≤95 
>160 
≥18y 
≤85% of LLN 
≥115% of ULN 
≤85% of LLN 
≥115% of ULN 
WBC/Leukocytes 
<12y 
109/L 
<3.5 
>15.0 
G/L 
<3.5 
>15.0 
≥12y 
<3.0 
>12.0 
<3.0 
>12.0 
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PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
Neutrophils Absolute 
>1m 
109/L 
<1.5 
G/L 
<1.5 
Lymphocytes 
<6m 
% 
≤30.0 
% 
≤30.0 
6m - <6y 
≤22.0 
≤22.0 
6y - <18y 
≤12.0 
≥80.0 
≤12.0 
≥80.0 
≥18y 
≤10.0 
≥80.0 
≤10.0 
≥80.0 
Basophils 
>1m 
% 
≥3.0 
% 
≥3.0 
Eosinophils 
>1m 
% 
≥10.0 
% 
≥10.0 
Monocytes 
>1m 
% 
≥20.0 
% 
≥20.0 
Platelets 
>1m 
109/L 
≤100 
>600 
G/L 
≤100 
>600 
RBC/ Erythrocytes 
<2y 
1012/L 
<3.0 
T/L 
<3.0 
≥2y 
<3.5 
<3.5 
Abbreviations: F=female; M=male; m=month; y= year. A month is defined as 30 days; a year is defined as 365.25 days. 
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12.1.2 
Blood chemistry 
 PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
AST (SGOT) 
<14y 
U/L 
>180 
U/L 
>180 
≥14y 
>144 
>144 
ALT (SGPT) 
1y - <18y 
U/L 
>90 
U/L 
>90 
≥18y 
>123 
>123 
Alkaline 
Phosphatase 
<4y 
U/L 
>690 
U/L 
>690 
4y - <10y 
>834 
>834 
10y - <18y 
>1174 
>1174 
≥18y 
>432 (F) 
>933 (M) 
>432 (F) 
>933 (M) 
GGT 
<6m 
U/L 
>522 
U/L 
>522 
6m - <1y 
>279 
>279 
1y - <13y 
>66 
>66 
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 PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
13y - <18y 
>126 
>126 
≥18y 
>255 
>255 
Total Bilirubin 
>1m 
mg/dL 
≥1.5 
umol/L 
≥25.656 
Total Protein 
2m-<1y 
g/dL 
<3.0 
>10.0 
g/L 
<30 
>100 
≥1y 
<4.3 
>10.0 
<43 
>100 
Albumin 
<1y 
g/dL 
<1.6 
>6.0 
g/L 
<16 
>60 
≥1y 
<2.4 
>7.0 
<24 
>70 
BUN 
<1y 
mg/dL 
>21 
mmol/L 
>7.497 
≥1y 
>30 
>10.71 
Urea 
<1y 
mg/dL 
>42 
mmol/L 
>7.014 
≥1y 
>60 
>10.02 
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 PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
Creatinine 
1y - <10y 
mg/dL 
>0.9 
umol/L 
>79.56 
10y - <16y 
>1.4 
>123.76 
≥16y 
>1.6 
>141.44 
Creatinine 
Clearance* 
All 
mL/min 
<70 
mL/s 
<1.169 
Calcium 
<1y 
mg/dL 
<6.9 
>12.2 
mmol/L 
<1.725 
>3.05 
1y - <18y 
<7.4 
>11.7 
<1.85 
>2.925 
≥18y 
<7.9 >11.1 
≤1.975 
≥2.775 
Phosphorous 
<1y 
mg/dL 
<1.8 
>8.2 
mmol/L 
<0.5814 
>2.6486 
≥1y 
<1.8 
>7.4 
<0.5814 
>2.3902 
Potassium 
<1y 
mEq/L 
<3.0 
>6.5 
mmol/L 
<3.0 
>6.5 
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 PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
≥1y 
<3.0 
>5.8 
<3.0 
>5.8 
Sodium 
>1m 
mEq/L 
≤130 
≥150 
mmol/L 
≤130 
≥150 
Glucose 
>1m 
mg/dL 
<50 
>180 
mmol/L 
<2.775 
>9.99 
Total Cholesterol 
1y - <18y 
mg/dL 
>250 
mmol/L 
>6.475 
≥18y 
>300 
>7.77 
LDL (calculated) 
1y - <18y 
mg/dL 
>140 
mmol/L 
>3.626 
≥18y 
>200 
>5.18 
HDL 
≤2y 
mg/dL 
<10 
mmol/L 
<0.259 
>2y 
<20 
<0.518 
Triglycerides 
<1y 
mg/dL 
>750 
mmol/L 
>8.475 
≥1y 
>250 
>2.825 
Uric Acid 
<1y 
mg/dL 
>7.7 
umol/L 
>457.996 
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 PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
1y - <13y 
>6.5 
>386.62 
13y - <18y 
>8.6 
>511.528 
≥18y 
>6.8 (F) 
>404.464 (F) 
>9.6 (M) 
>571.008 (M) 
Thyroxine (T4) 
<1y 
ug/dL 
≤4.3 
nmol/L 
≤55.3453 
≥18.4 
≥236.8264 
≥1y 
≤3.8 
≤48.9098 
≥13.5 
≥173.7585 
Globulin 
<1y 
g/dL 
<1.0 
g/L 
<10 
>3.8 
>38 
≥1y 
<1.2 
<12 
>4.4 
>44 
Abbreviations: ALT= alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; dL = deciliter; F=female; GGT: 
gamma-glutamyltransferase; HDL = high density lipoprotein; LDL = low density lipoprotein; L = liter; M=male; m = month (a month is defined 
as 30 days) mg = milligram; mmol = millimoles; μg = microgram; U = unit; ULN = upper limit of normal; y = years (a year is defined as 365.25 
days). *Schwartz equation (patients <12):   Cr Cl ml/min = [Height (cm) * 0.55] / serum creatinine Cockroft equation (patients >12): Male: Cr Cl 
ml/min = [(140-age) x body weight (kg)] / (72 x serum creatinine); Female: Cr Cl ml/min = [(140-age) x body weight (kg)] / (72 x serum 
creatinine)] x 0.85 
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12.1.3 
Urinalysis 
Qualitative urine parameters are generally reported by a descriptive score, which differs among 
laboratories. For data analysis purpose, a four-point scale is used. Five-point, six- point, or 
seven-point scales will be collapsed into a four-point scale first. A value is considered possibly 
clinically significant treatment emergent abnormal if an upward shift of at least 2 degrees from 
the baseline occurs under investigational treatment. To collapse the results in a five-point scale 
into a four-point scale, the lowest two positive results will be combined (see example below). 
For results reported with a scale of more than five-point, please consult your study physician for 
how to collapse into four-point scale. 
Original Five-point Scale 
Four-point Scale 
Negative/None 
Negative/None 
Trace/Rare/Mild/A Few 
Trace/1+/Rare/Mild/A Few 
1+ 
 
2+/Mod 
2+/Mod 
3+/Sev 
3+/Sev 
 
 
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12.2 
VITAL SIGN ASSESSMENTS - ABNORMAL 
Abnormality criteria to be applied in the assessment of vital signs parameter values are given below. 
PARAMETER 
AGE RANGE 
ABNORMALITY CRITERIA 
Pulse Rate 
(beats/minute) 
<6m 
<100 
>180 
6m - <3y 
<90 
>150 
3y - <12y 
<60 
>130 
12y - <17y 
<50 
>120 
≥17y 
<50 and a decrease from Baseline of ≥15 
>120 and an increase from Baseline of ≥15 
Systolic Blood 
Pressure (mmHg) 
<6m 
<60 
>100 
6m - <3y 
<70 
>120 
3y - <12y 
<80 
>140 
12y - <17y 
<90 
>160 
≥17y 
≤ 90 and a decrease from Baseline of ≥20 
≥ 180 and an increase from Baseline of ≥20 
Diastolic Blood 
Pressure (mmHg) 
<6m 
<40 
>65 
6m - <3y 
<45 
>75 
3y - <12y 
<50 
>80 
12y - <17y 
<50 
>105 
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≥17y 
<50 and a decrease from Baseline of ≥15 
>105 and an increase from Baseline of ≥ 15 
Respiratory Rate 
(breaths/minute) 
<6m 
<25 
>55 
6m - <3y 
<20 
>45 
3y - <12y 
<15 
>35 
≥12y 
<10 
>25 
Body Weight 
1m - <17y 
<3% or 97% of the normal body weight growth 
curve ranges based on gender and the age of subject 
on date of weight assessmenta 
≥17y 
≥ 10% change from Baseline (an increase or a 
decrease)a 
Abbreviations: m = month, y = year. A month is defined as 30 days; a year is defined as 365.25 days. 
asource: http://www.cdc.gov/growthcharts/ 
 
 
 
 
 
 
 
 
 
 
 
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12.3 
ELECTROCARDIOGRAM (ECG) – ABNORMAL 
Abnormality criteria to be applied in the assessment of ECG parameter values are given below: 
Parameter 
Age 
Abnormality Criteria 
QT interval (ms) 
1m-<12y 
>500 
>12y 
>500 or ≥60ms increase from Baseline 
QTc(F) (ms) 
<6m 
>490, or >15% increase from Baseline 
6m-<3y 
>440, or >15% increase from Baseline 
3y-<12y 
>440, or >15% increase from Baseline 
>12y- <17y 
>440, or >15% increase from Baseline 
≥17y 
>500 or ≥60ms increase from Baseline 
QTc(B) (ms) 
<6m 
>490, or >15% increase from Baseline 
6m-<3y 
>450, or >15% increase from Baseline 
3m-<12y 
>450, or >15% increase from Baseline 
>12y- <17y 
>450, or >15% increase from Baseline 
≥17y 
>500 or ≥60ms increase from Baseline 
PR interval (ms) 
<6m 
>150, or >25% increase from Baseline 
6m-<3y 
>170, or >25% increase from Baseline 
3y-<12y 
>180, or >25% increase from Baseline 
>12y - <17y 
>200, or >25% increase from Baseline 
≥17y 
Treatment-emergent value >200, >220, >250 
QRS interval (ms) 
<6m 
>90, or >25% increase from Baseline 
6m-<3y 
>90, or >25% increase from Baseline 
3y-<12y 
>100, or >25% increase from Baseline 
>12y - <17y 
>110, or >25% increase from Baseline 
≥17y 
Treatment-emergent value >100, >120, >140 
Heart rate (bpm) 
<6m 
<100, >180 
6m-<3y 
<90, >150 
3y-<12y 
<60, >130 
>12y 
<50, >120 
Abbreviations: bpm = beats per minute; m = months; ms = milliseconds; QTc = corrected QT 
interval; y = years. A month is defined as 30 days; a year is defined as 365.25 days. 
Note: Treatment-emergent is defined as meeting the criteria at any post-Baseline visit and not 
meeting the same criteria during Baseline 
 
 
 
 
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13 
AMENDMENT(S) TO THE SAP 
13.1 
Amendment 1 
Rationale for the amendment 
The primary purpose of this amendment is to add the analyses for Potentially Drug Induced 
Liver Injury (PDILI) and provide clarifications to the planned analyses according to the current 
program standards.    
Modifications and Changes 
Major specific changes 
Change #1  
3.2.1 Analysis timepoints 
3.2.1.1 First and last dose of UCB0942 
Throughout this SAP, and unless otherwise stated, the “first dose of UCB0942” refers to the first 
UCB0942 administration in the EP0073 study. This is the first administration after the subject 
has filled in the EP0069 completion form and has returned the unused EP0069 UCB0942 tablets 
and empty containers. The first UCB0942 administration is planned to be the evening dose of the 
Entry Visit (V2; ie, not the first UCB0942 administration from any previous studies that subjects 
might have participated). Throughout this SAP, the “last dose of UCB0942” refers to the last 
dose of UCB0942 that was administered at any EP0073 study period; Evaluation or Taper 
Period. 
3.2.1.2 Relative day  
The relative day of an event will be derived with the start date of first UCB0942 administration 
in EP0073 as reference date, up to and including the last day of UCB0942 administration. 
Relative days for an event or measurement occurring before the reference date will have a ‘-’ 
prefix and will be calculated as follows: 
Relative Day=−[(Event Date-Reference Date)] 
Relative days for an event or measurement occurring on or after the reference date to the last day 
of UCB0942 administration are calculated as follows: 
Relative Day=[(Event Date-Reference Date)+1] 
For events or measurements occurring after the date of last dosing (as defined above), the 
relative day will be calculated with the date of last UCB0942 administration as reference. 
Relative day in this case will be prefixed with ‘+’ in the data listings and will be calculated as 
follows: 
Relative Day=+[(Event Date-Reference Date)] 
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There is no relative Day 0. Relative day is not calculated for partial dates in cases where relative 
day is shown in a subject data listing. In such cases, relative day should be presented as ‘--’ in 
the subject data listings. 
3.2.1.3 Study periods 
For seizure endpoints and safety parameters, the Baseline used is the EP0069 2 week Prospective 
Outpatient Baseline Period. 
The study is divided into 4 periods: Screening Period, Evaluation Period, Taper Period, and SFU 
Period. The following periods and sub-periods will be considered in the definition of efficacy 
and safety variables (for details see Section 2.2.2.3): 
• 
A 2-week Screening Period from V13 to V15 (Days OP43 to OP57) of the 8-week Outpatient 
Maintenance Period of the EP0069 study. 
• 
Evaluation Period: The approximate five-year Treatment Period, with the following sub 
periods. 
− 1st Year 
− 2nd Year 
− 3nd Year 
− 4th Year 
− 5th Year 
• 
Taper Period. 
• 
SFU Period.  
3.2.1.4 Monthly time intervals  
A month is defined as 30 days and time intervals based on monthly durations are defined as a 
multiple of 30 days (eg, 12 months is defined as 360 days). The following definitions of 3-month 
and 6-month intervals are based on 30-day months where the date of first dose of UCB0942 in 
EP0073 is Day 1: 
Interval Duration Definition: 
- 
Months 1-3 Days 1-90 
- 
Months 4-6 Days 91-180 
- 
Months 7-9 Days 181-270 
- 
Months 10-12 Days 271-360 
Subsequently, 3- and 6-month intervals are defined in a similar manner. Three-month intervals 
will be used for analysis of efficacy outcomes and AEs. 
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For the analysis of efficacy outcomes, a subject is included in the analysis for a 3-month interval 
if the subject remained in the study for at least 83 days of the 3-month interval and the subject 
diary was completed for at least 1 day during the 3-month interval.  
For the analysis of AEs, a subject is included in the analysis for a 3-month interval if the subject 
is ongoing for at least one (whole or partial) day of the interval. 
3.2.1.5 Last Value on UCB0942 Treatment  
Last Value for safety parameters (such as clinical laboratory parameters, vital signs, ECGs) is the 
last available result obtained after the first dose of UCB0942 and prior to or on the date of last 
dose of UCB0942. All scheduled and unscheduled assessments within this time period will be 
considered. Last Value will be determined separately for each laboratory parameter for 
hematology, chemistry, urinalysis assessments. A similar definition applies for summaries based 
on regulatory submission interim cutoffs for subjects who have discontinued the study prior to 
the clinical cutoff date. For subjects who are ongoing at the time of the clinical cutoff date, Last 
Value will be the last result obtained from any scheduled or unscheduled visit prior to or on the 
date of the clinical cutoff.  
3.2.1.6 Exposure duration and exposure duration cohorts 
At the final analysis, the overall duration of exposure (or On Treatment Period) will be 
calculated as the date of last dose of UCB0942 minus the date of first dose of UCB0942 in 
EP0073 plus 1 day. The following rules apply for analyses based on clinical cutoffs. For subjects 
who have discontinued prior to or on the date of the clinical cutoff, the overall duration of 
exposure will be calculated as the date of last dose of UCB0942 on or prior to the date of the 
clinical cutoff minus the date of first dose of UCB0942 plus 1 day. For subjects who are ongoing 
at the time of the clinical cutoff, the overall duration of exposure will be calculated as the date of 
last scheduled or unscheduled visit on or prior to the date of the clinical cutoff minus the date of 
first dose of UCB0942 plus 1 day. 
Each subject will be classified into one or more of the following exposure duration cohorts based 
on the duration of UCB0942 exposure as calculated above: 
All Subjects:  
≥1 day 
≥3 months   = ≥90 days 
≥6 months   = ≥180 days 
≥12 months = ≥360 days 
≥18 months =  ≥540 days 
≥24 months =  ≥720 days 
   and then yearly  ≥ 3, 4, 5 years 
 
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For summaries based on clinical cutoffs, this categorization will continue in 6-month increments 
past 12 months up to a timepoint that will be determined based on cumulative exposure at the 
time of the clinical cutoff. 
3.2.1.7 Study visit cohorts 
Study visit cohorts are defined for summaries of QOLIE-31-P. Six-month, 12-month, 18-month, 
and 24-month, 3-, 4-, 5 year cohorts are defined. Subjects will be classified into a study visit 
cohort if they attend the scheduled visit at the timepoint defined by the cohort. For example, 
subjects will be included in the 18-month study visit cohort if they attend the scheduled visit at 3 
months (i.e., FEV at Month 3, V5). Subjects may be classified in more than 1 cohort. Generally, 
subjects included in a cohort for a later visit will be included in all earlier study visit cohorts 
(e.g., 6-month and 12-month study visit cohorts for subjects in the 18-month study visit cohort), 
although this may not be the case in the event of a missed visit or if an unscheduled visit is 
conducted in lieu of a scheduled visit. 
Has been changed to: 
3.2.1 Analysis periods 
Unless noted otherwise, Baseline is the EP0069 2 week Prospective Outpatient Baseline Period. 
The study is divided into 4 periods: Screening Period, Evaluation Period, Taper Period, and SFU 
Period. The following periods will be considered in the definition of efficacy and safety 
variables: 
• 
A 2-week Screening Period from V13 to the day before V15 of the 8-week Outpatient 
Maintenance Period of the EP0069 study. 
• 
Evaluation Period:  Entry Visit (EV) to Last Evaluation Period Visit (LEPV) or Early 
Discontinuation Visit (EDV) or clinical data cutoff date if the subject is ongoing and does not 
have the EDV. The EV is also V15 of EP0069. Data in EP0073 database will be used in the 
analyses when possible.    
• 
Taper Period: the day after LEPV or EDV to End of Taper Visit or clinical data cutoff date if 
the subject is ongoing. 
• 
SFU Period: The day after the End of Taper Visit to date of final contact or clinical data 
cutoff date if the subject is ongoing.  
In addition, the On-Treatment Period is defined as from the date of first dose to the date of last 
dose of UCB0942 in EP0073 (Section 3.2.2).  
At the time of a clinical cutoff prior to the study completion, a subject will be classified as 
“discontinued” if the Study Completion CRF is available and the date of premature study 
termination is provided. All other subjects will be classified as “ongoing.” Only the data on or 
prior to the clinical cutoff date will be included in the analyses.   
3.2.2 First and last dose of UCB0942 
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Throughout this SAP, and unless otherwise stated, the first dose (of UCB0942) refers to the first 
UCB0942 administration in the EP0073 study reported on First Administration of Study 
Medication case report form (CRF). The last dose (of UCB0942) refers to the date of last 
administration of study medication reported on Study Completion CRF, at any EP0073 study 
period, Evaluation or Taper Period. 
At the time of a clinical cutoff, for subjects who are ongoing and not in the SFU Period, the last 
dose of UCB0942 will be set to the date of the clinical cutoff for the interim analyses. For 
subjects who are ongoing and in the SFU Period (ie, had the End of Taper Visit) at the time of a 
clinical cutoff, the last dose of UCB0942 will be set to the last dosing date on the Drug Dosing 
Log CRF for the interim analyses.  
3.2.3 Relative day  
The relative day of an event will be derived with the start date of first UCB0942 administration 
in EP0073 as reference date, up to and including the last day of UCB0942 administration. 
Relative days for an event or measurement occurring before the reference date will have a 
‘-’ prefix and will be calculated as follows: 
Relative Day=−[(Event Date-Reference Date)] 
Relative days for an event or measurement occurring on or after the reference date to the 
last day of UCB0942 administration are calculated as follows: 
Relative Day=[(Event Date-Reference Date)+1] 
For events or measurements occurring after the date of last dosing (as defined above), the 
relative day will be calculated with the date of last UCB0942 administration as reference date. 
Relative day in this case will be prefixed with ‘+’ in the data listings and will be calculated as 
follows: 
Relative Day=+[(Event Date-Reference Date)] 
There is no relative Day 0. Relative day is not calculated for partial dates in cases where relative 
day is shown in a subject data listing. In such cases, relative day should be presented as ‘--’ in 
the subject data listings. 
3.2.4 Monthly time intervals  
A month is defined as 30 days and time intervals based on monthly durations are defined as a 
multiple of 30 days (eg, 12 months is defined as 360 days).  
Interval Duration Definition: 
- 
Months 0-3: Days 1-90 
- 
Months >3-6: Days 91-180 
- 
Months >6-9: Days 181-270 
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- 
Months >9-12: Days 271-360 
Subsequent 3-month intervals are defined in a similar manner.  
For the analysis of efficacy variables during the Evaluation Period, 3-month intervals will be 
derived for the Evaluation Period. For the analysis of AEs and safety variables, 3-month intervals 
will be derived for the On-Treatment Period.  
3.2.5 Last Value during the On-Treatment Period  
Last Value for safety parameters (such as clinical laboratory parameters, vital signs, ECGs) is the 
last available result obtained prior to or on the date of last dose of UCB0942 in EP0073. All 
scheduled and unscheduled assessments within this time period will be considered. Last Value 
will be determined separately for each laboratory parameter for hematology, chemistry, 
urinalysis assessments. Similarly, the minimum and maximum values are defined as the 
minimum and maximum values prior to or on the date of last dose of UCB0942.  
3.2.6 Completer Cohort 
Because the duration of the Evaluation Period varies among the subjects, each subject will be 
classified into one or more of the following completer cohorts based on the duration of the 
Evaluation Period: 
≥3 months   : ≥90 days 
≥6 months   : ≥180 days 
≥12 months : ≥360 days 
≥18 months :  ≥540 days 
≥24 months :  ≥720 days 
≥36 months :  ≥1080 days 
≥48 months :  ≥1140 days 
≥60 months =  ≥1800 days 
The duration of the Evaluation Period is calculated as the date of the end of the Evaluation 
Period – EV +1. Selected efficacy variables will be analyzed by completer cohorts.   
3.2.7 Mapping of data from early discontinuation visits 
If an EDV occurs at the day of a scheduled visit, in-clinic safety and PK assessments should 
correspond to that scheduled visit. Safety assessments at an EDV that occurs on a day between 
two scheduled visits will be assigned to the next scheduled visit. No mapping will be performed 
for the seizure and QOLIE-31-P data collected at the EDV.  
In the by-visit summary tables, only nominal (scheduled) visits (after mapping) where the 
assessment is scheduled will be included. Unscheduled visits will not be mapped to scheduled 
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visits. In the subject listing, data will be presented under the actual visits, including EDV and 
unscheduled visits. 
Change #2 
6.2 Medical history and concomitant diseases 
Medical history and ongoing medical conditions for EP0073 will be listed and summarized for 
the SS and MedDRA® system organ class (SOC) and preferred term (PT). The start date (month 
and year only) and end date (or ongoing if applicable) will also be included in the listing. 
Epilepsy history will not be included in these tables. 
Procedure history at the time of entry into the EP0073 study will be listed separately by the 
procedure reported term for the SS.  
Concomitant medical procedures carried out during the study will be listed for the SS. 
6.2.1 History of epilepsy 
All of the following are summarized using data collected at the time of entry into the EP0069 
study. 
The history of epilepsy will be listed for all subjects in the SS.  
Etiology of epilepsy 
The number and percentage of subjects with each type of etiology as specified in the EP0069 
eCRF (genetic, congenital, etc) will be summarized for the FAS. 
Epileptic seizure profile 
The number and percentage of subjects experiencing each seizure type at any time prior to the 
study entry will be summarized for the FAS based on the ILAE Seizure Classification History 
EP0069 eCRF (historical seizures count). 
The overall number and percentage of subjects with a history of type I seizures and the overall 
number and percentage of subjects with a history of type II seizures will also be summarized. A 
subject will be classified as having a history of type I seizures if the subject has a history of IA, 
IA1, IA2, IA3, IA4, IB, IB1, IB2, or IC seizures. A subject will be classified as having a history 
of type II seizures if the subject has a history of IIA, IIB, IIC, IID, IIE, or IIF seizures. 
Focus localization 
The number and percentage of subjects with each category of focus localization (unknown, 
frontal, temporal, parietal, occipital) will be summarized for the FAS. Subjects may be counted 
in more than 1 category of focal localization. 
History of epileptic seizures 
History of epileptic seizures, including the number and percentage of subjects with a history of 
status epilepticus, the number and percentage of subjects with a history of withdrawal seizures, 
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and quantitative summaries of epilepsy duration, age at onset of first seizure, and percent of life 
with epilepsy, will be summarized for the FAS. 
Seizure types experienced during Baseline 
The number and percentage of subjects experiencing each seizure type during the EP0069 2 
week Prospective Outpatient Baseline Period will be summarized for the FAS based on data 
from the subjects’ seizure diaries. The following seizure types will be summarized: I, IA, IB, IC, 
II, IIA through IIF, III, and IV. 
Subjects will be counted for all higher levels of seizure type categories corresponding to the 
seizure types or seizure sub-types reported on the EP0069 eCRF. For example, subjects with an 
IA1 seizure will be counted for types I and IA.  
The Baseline 28 day adjusted POS frequency will also be summarized at Baseline. 
6.3 Prior and concomitant medications 
The medications will be classified as AEDs or non AEDs during the DEM.   
For interim analyses, any non coded terms will report the levels as UNCODED in the listing.  
Prior medication definition 
‘Prior medication’ is any medication that started prior to the date of first UCB0942 
administration in EP0073. 
Concomitant medication definition 
‘Concomitant medication’ is any medication that has been taken for at least 1 day between the 
first UCB0942 administration in EP0073 and the end of study. This definition includes the 
following: 
- 
Prior medication not stopped before the date of the first UCB0942 administration in EP0073 
- 
When the start date is between the date (including the date) of the first UCB0942 
administration in EP0073 and the final study visit or, in case of early termination, on the date of 
the subject’s last visit 
Medications may be both prior and concomitant. 
6.3.1 Non- Antiepileptic drugs 
All non-AED medications will be listed for the SS by WHODD Anatomical Main Group [Level 
1], Therapeutic Subgroup [Level 2], PT and reported term.  
The number and percentage of subjects taking non-AED medications at entry into EP0069 will 
be summarized for the SS by WHODD Anatomical Main Group [Level 1], Therapeutic 
Subgroup [Level 2], and PT. 
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The number and percentage of subjects taking concomitant non-AED medications at entry into 
EP0073 will be summarized separately for the SS by WHODD Anatomical Main Group [Level 
1], Therapeutic Subgroup [Level 2], and PT for the whole study period.  
6.3.2 Antiepileptic drugs  
Prior and concomitant AED medications will be listed separately for the SS by WHODD 
Therapeutic Subgroup [Level 2], Chemical [Level 4], PT and reported term.  
Prior AED Medications  
The number and percentage of subjects taking AED medications prior to EP0073 will be 
summarized for the SS by PT. These are prior and concomitant AED medications from the 
EP0069 study. 
Number of prior AEDs 
The number of AEDs taken prior to EP0073 will be summarized for the SS based on the 
following categorization: <4, 4 or 5, 6 or 7, 8 to 10, >10 AEDs.  
Previous AEDs by reason for AED discontinuation  
The number and percentage of subjects by reason for discontinuation of previous AEDs prior to 
EP0073 will be summarized for the SS. Percentages for each reason for discontinuation will be 
relative to the number of subjects taking each AED. 
Use of vagus nerve stimulation  
The number and percentage of subjects with active vagus nerve stimulation (VNS), and the 
number and percentage of subjects with no VNS implant or a non active VNS implant prior to 
EP0073 will be summarized for the SS. 
All other VNS data (eg, use of magnet, VNS settings) will be listed but will not be summarized. 
Number of AEDs taken at EP0073 study entry 
The number and percentage of subjects taking 1, 2, and ≥3 AEDs at the time of EP0073 study 
entry will be summarized for the SS. The same summary will be reported separately by VNS use 
at study entry (no VNS or VNS not active versus currently active VNS). 
Levetiracetam use at EP0073 study entry 
The number and percentage of subjects in each LEV use category at EP0073 study entry will be 
summarized for the SS: 
1. LEV prior and current use (concomitant use of LEV at study entry). 
2. LEV Prior Use Only=History of prior LEV use and must have discontinued 4 weeks prior to 
study entry. 
3. LEV Naïve=No history of prior LEV use, and no use at study entry. 
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Concomitant AED Medications 
The number and percentage of subjects taking concomitant AED medications during EP0073 
will be summarized separately for the SS by PT for the whole study period. 
Has been changed to: 
6.2 Medical history and concomitant diseases 
Medical history and ongoing medical conditions for EP0073 will be listed and summarized for 
the SS and MedDRA® system organ class (SOC) and preferred term (PT). The start date (month 
and year only) and end date (or ongoing if applicable) will also be included in the listing. 
Epilepsy history will not be included in these tables. 
The summary of medical history will be based on the medical history at the time of entry into 
EP0069 and any updates at EV. 
Concomitant medical procedures carried out during the study will be listed for the SS. 
6.2.1 History of epilepsy 
All of the following are summarized using data collected at the time of entry into the EP0069 
study. The history of epilepsy will be listed and summarized for all subjects in the SS.  
Epileptic seizure profile 
The number and percentage of subjects experiencing each seizure type at any time prior to the 
study entry will be summarized for the SS based on the ILAE Seizure Classification History 
EP0069 eCRF (historical seizures count). 
The overall number and percentage of subjects with a history of type I seizures and the overall 
number and percentage of subjects with a history of type II seizures will also be summarized. A 
subject will be classified as having a history of type I seizures if the subject has a history of IA, 
IA1, IA2, IA3, IA4, IB, IB1, IB2, or IC seizures. A subject will be classified as having a history 
of type II seizures if the subject has a history of IIA, IIB, IIC, IID, IIE, or IIF seizures. 
History of epileptic seizures 
History of epileptic seizures, including the number and percentage of subjects with a history of 
status epilepticus, the number and percentage of subjects with a history of withdrawal seizures, 
and quantitative summaries of epilepsy duration relative to the Entry Visit of EP0073 (ie, Entry 
Visit of EP0073 minus the date of the first epileptic seizure plus 1 divided by 365.25), age at 
onset of first seizure relative to the Entry Visit of EP0073, and percent of life with epilepsy 
relative to the Entry Visit of EP0073, will be summarized for the SS. 
6.3 Other Baseline Characteristics 
The following data collected at the time of entry into the EP0069 study will be summarized for 
the SS. The parameters derived in EP0069 will be directly used.  
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Number of past AEDs  
The number of past AEDs taken prior to EP0069 will be summarized for the SS based on the 
following categorization: <4, 4 or 5, 6 or 7, 8 to 10, >10 AEDs.  
Number of prior AEDs 
The number of AEDs taken prior to EP0069 will be summarized for the SS based on the 
following categorization: <4, 4 or 5, 6 or 7, 8 to 10, >10 AEDs.  
Use of vagus nerve stimulation  
The number and percentage of subjects with active vagus nerve stimulation (VNS), and the 
number and percentage of subjects with no VNS implant or a non active VNS implant prior to 
EP0069 will be summarized for the SS. 
Number of AEDs taken at EP0069 study entry 
The number and percentage of subjects taking 1, 2, and ≥3 AEDs at the time of EP0069 study 
entry will be summarized for the SS. 
Levetiracetam use at EP0069 study entry 
The number and percentage of subjects in each LEV use category at EP0069 study entry will be 
summarized for the SS: 
LEV prior and current use (concomitant use of LEV at study entry). 
LEV Prior Use Only=History of prior LEV use and must have discontinued 4 weeks prior to 
study entry. 
LEV Naïve=No history of prior LEV use, and no use at study entry. 
6.4 Concomitant medications 
The medications will be classified as AEDs or non AEDs. For interim analyses, any non coded 
terms will report the levels as UNCODED in the listing and table.  
Medications will be considered as concomitant if 
- 
the start date of the medication is on or after the date of first dose of UCB0942 in EP0073 
and the start date is not after the date of last dose in EP0073 
- 
Or the start date is prior to the first dose of UCB0942 in EP0073 but the stop date is after the 
first dose in EP0073 or ongoing.  
6.4.1 Non- Antiepileptic drugs 
All concomitant non-AED medications will be listed for the SS by WHODD Anatomical Main 
Group [Level 1], Therapeutic Subgroup [Level 2], PT and reported term.  
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The number and percentage of subjects taking concomitant non-AED medications during 
EP0073will be summarized separately for the SS by WHODD Anatomical Main Group [Level 
1], Therapeutic Subgroup [Level 2], and PT for the whole study period.  
6.4.2 Concomitant AEDs 
Concomitant AED medications will be listed separately for the SS by WHODD Therapeutic 
Subgroup [Level 2], Chemical [Level 4], PT and reported term.  
The number and percentage of subjects taking concomitant AED medications will be 
summarized by chemical/therapeutic/pharmacological subgroup (ATC classification level 4), and 
preferred drug name for the SS. 
Change #3 
7 MEASUREMENTS OF TREATMENT COMPLIANCE 
At each visit after UCB0942 is dispensed, subjects must return all unused UCB0942 and empty 
UCB0942 containers. Compliance will be calculated as 100 times the dose (tablets) taken 
divided by the planned dose (tablets) that should have been taken. If a subject withdraws from 
the study during a treatment period, their compliance will be calculated up to the time that they 
dropped out. After a subject has dropped out, the compliance should not be set to zero.  
Compliance will be listed and summarized for the SS. The number and percentage of subjects 
with compliance levels <75%, 75% to 120%, and >120% will be summarized for the first year. 
Has been changed to: 
7 MEASUREMENTS OF TREATMENT COMPLIANCE 
Information reported on the CRF regarding tablets/bottles dispensed and returned will be 
reported in subject data listings. Treatment compliance will be evaluated through the review of 
important protocol deviations. 
Change #4 
The following has been added: 
8.2.8 Time to discontinuation 
Kaplan-Meier estimates of the percentage of subjects completing 3, 6, 12, 18, 24, 36, 48, and 60 
months of treatment will be provided. The corresponding Kaplan-Meier plot will also be 
provided. For subjects who discontinued from the study, the event date is set to the date of last 
dose of UCB0942 and the time to event will be calculated as the date of last dose minus the date 
of first dose of UCB0942 in EP0073 plus 1. Subjects who completed the study will be censored 
as of the date of last dose of UCB0942. At a clinical cutoff, subjects who are ongoing will be 
censored as of the date of last dose of UCB0942 defined for the interim analyses (Section 3.2.2). 
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Change #5 
9.1 Non compartmental pharmacokinetics analyses 
Plasma concentrations of UCB0942, 
, and 
 will be 
determined from blood samples obtained in the study during the first year (V3, V4, V5, V6, V7, 
V8, V9).  
The individual concentrations of UCB0942, 
, and 
 will be 
listed for the FAS. 
Individual concentrations will be summarized by visit using n, mean, median, SD, minimum, 
maximum, geometric mean, and geoCV and 95% CI (assuming log-normally distributed data). 
This table will be repeated for UCB0942, 
, and 
 
Has been changed to: 
9.1 Plasma concentrations 
Plasma concentrations of UCB0942, 
, and 
 will be 
determined from blood samples obtained in the study during the first year (V3, V4, V5, V6, V7, 
V8, V9).  
The individual concentrations of UCB0942, 
, and 
 will be 
listed for the FAS with blood sampling dates/times and elapsed time from last administration. 
Unless otherwise stated, measured values below the limit of quantification (BLQ) will be 
reported as LLOQ/2. 
The concentrations of UCB0942 from samples taken 1-3 hours and 10-12 hours after the most 
recent UCB0942 administration will be summarized by visit using n, mean, median, SD, 
minimum, maximum, geometric mean, and geoCV and 95% CI of the geometric mean. This 
table will be repeated for UCB0942, 
 and 
 PK samples 
taken at other timepoints will be included in the subject listing but not summarized. 
Change #6 
10.1 
Extent of exposure 
All UCB0942 administration information will be listed by subject.  
A daily dose will be calculated for each study day from the day of first dose of UCB0942 to the 
day of last dose of UCB0942 for the purposes of calculating modal dose. Daily dose will be 
calculated as the sum of the AM and PM dose for each day. 
Modal daily doses will be calculated across all study days on or after the day of first dose of 
UCB0942 and up to and including the day of last dose of UCB0942. Modal daily dose is the 
most frequently taken daily dose during this period. In the event of a tie, the modal dose will be 
set to the lower of the tied doses. Modal daily dose will be categorized as follows: 
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Category 
Definition 
200mg/day 
≤ 200mg/day 
400mg/day 
>200mg/day to ≤400mg/day 
600mg/day 
>400mg/day to ≤600mg/day 
800mg/day 
>600mg/day 
Subject years of exposure will be calculated by summing the exposure duration in days for all 
subjects being summarized, and dividing the resulting value by 365.25. 
The number and percentage of subjects exposed to UCB0942 will be summarized overall and by 
modal dose category. The number and percentage of subjects in each Exposure Duration Cohort 
(≥3 months, ≥6 months, ≥12 months, and so forth) will be summarized. 
The number and percentage of subjects within each modal dose category will be summarized for 
each Exposure Duration Cohorts; percentages will be relative to the total number of subjects in 
each Exposure Duration Cohort. 
Has been changed to: 
10.1 
Extent of exposure 
All UCB0942 administration information will be listed by subject.  
A daily dose will be calculated for each study day from the day of first dose of UCB0942 to the 
day of last dose of UCB0942 for the purposes of calculating modal dose. Daily dose will be 
calculated as the sum of the AM and PM dose for each day. 
Modal daily doses will be calculated across all study days on or after the day of first dose of 
UCB0942 and up to and including the day of last dose of UCB0942. Modal daily dose is the 
most frequently taken daily dose during this period. In the event of a tie, the modal dose will be 
set to the lower of the tied doses. Modal daily dose will be categorized as ≤200mg/day, 
>200mg/day to ≤400mg/day, >400mg/day to ≤600mg/day, >600mg/day to ≤800mg/day, and 
>800mg/day.  
For subjects who completed or discontinued from the study, the overall duration of exposure will 
be calculated as the date of last dose of UCB0942 minus the date of first dose of UCB0942 in 
EP0073 plus 1 day. For ongoing subjects at a clinical cutoff, the duration of exposure will be 
calculated based on the date of last dose of UCB0942 defined for the interim analyses (Section 
3.2.2). Subject years of exposure will be calculated by summing the exposure duration in days 
for all subjects being summarized, and dividing the resulting value by 365.25. 
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The number and percentage of subjects exposed to UCB0942 will be summarized overall and by 
modal dose category. The number and percentage of subjects exposed for ≥3, ≥6, ≥12, ≥18, ≥24, 
≥36, ≥48, and ≥60 months will be summarized. 
Change #7 
10.2.1 Definition of treatment-emergent AE 
Adverse events will be classified as either prior, concomitant, or treatment-emergent.  
A prior AE is defined as any AE which had onset prior to the date of the first dose of UCB0942 
in EP0073. A concomitant AE is defined as any AE which is ongoing at any time between the 
first dose of UCB0942 in EP0073 and prior to the end of the study. 
A treatment-emergent adverse event (TEAE) is defined as any event not present prior to the first 
dose of UCB0942 in EP0073 or any unresolved event already present before administration of 
UCB0942 that worsens in intensity following exposure to the treatment. 
Where dates are missing or partially missing, AEs will be assumed to be treatment-emergent, 
unless there is clear evidence (through comparison of partial dates, see Section 4.2) to suggest 
that the AE started prior to the first dose of study treatment. AEs with an incomplete onset date 
will be classified as TEAEs if the month and year of onset (when only the month and year are 
specified) is the same as the month and year of the first UCB0942 dose or the year of onset 
(when only year is specified) is the same as the year of first UCB0942 dose. 
10.2.2 General summaries of TEAEs 
Listings will be provided for all AEs, SAEs, AEs leading to taper, AEs leading to withdrawal, 
and AEs leading to death by subject for the SS. 
The number and percentage of subjects who experience TEAEs will be summarized by SOC and 
PT, overall and by 3-month time intervals.  
The following tabular summaries will be presented for the SS: 
• 
Incidence of AEs - Overview  
• 
Incidence of TEAEs  
• 
Incidence of TEAEs by Period (Evaluation, Taper, SFU) 
• 
Incidence of Serious TEAEs  
• 
Incidence of TEAEs by Relationship 
• 
Incidence of SAEs by Relationship 
• 
Incidence of Non-Serious TEAEs by Relationship 
• 
Incidence of Fatal TEAEs by Relationship 
• 
Incidence of TEAEs by Maximum Relationship  
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Statistical Analysis Plan 
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• 
Incidence of TEAEs by Intensity 
• 
Incidence of TEAEs by Maximum Intensity 
• 
Incidence of TEAEs leading to Taper  
• 
Incidence of TEAEs leading to Withdrawal  
• 
Incidence of TEAEs occurring in at least 2% of Subjects  
• 
Incidence of TEAEs by Dose at Onset 
• 
Incidence of Non-Serious TEAEs above the Threshold of 5% of Subjects 
• 
Incidence of Non-Serious TEAEs above the Threshold of 5% of Subjects by Relationship 
Summary tables will contain counts of subjects, percentages of subjects in parentheses and the 
number of events where applicable. A subject who has multiple events in the same SOC and PT 
will be counted only once in the subject counts but all events will be included. 
In summaries including relationship to study treatment, the following relationships will be 
summarized: ‘Not related’, ‘Related’. Subjects who experience the same event multiple times 
will be included in the most related category. Events with missing relationship will be considered 
as ‘Related’ to the last given study product for summary purposes but recorded as missing in the 
listings. 
In summaries including intensity, the following intensity categories will be summarized: ‘Mild’, 
‘Moderate’, ‘Severe’. Subjects who experience the same event multiple times will be included in 
the most severe category. Events with missing intensity will be considered as ‘Severe’ events for 
summary purposes but recorded as missing in the listings. 
Adverse event summaries will be ordered in terms of decreasing frequency for SOC, and PT 
within SOC. 
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Has been changed to: 
10.2.1 Definition of treatment-emergent AE 
A treatment-emergent adverse event (TEAE) is defined as 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.  
Where dates are missing or partially missing, AEs will be assumed to be treatment-emergent, 
unless there is clear evidence (through comparison of partial dates, see Section 4.2) to suggest 
that the AE started prior to the first dose of study treatment. AEs with an incomplete onset date 
will be classified as TEAEs if the month and year of onset (when only the month and year are 
specified) is the same as the month and year of the first UCB0942 dose or the year of onset 
(when only year is specified) is the same as the year of first UCB0942 dose. TEAEs are assigned 
into an analysis period or time interval based on the onset date. 
10.2.2 General summaries of TEAEs 
Listings will be provided for all AEs, SAEs, AEs leading to discontinuation (ie, drop out), and 
AEs leading to death by subject for the SS. 
Unless noted otherwise, TEAEs during the study (including the Taper and SFU Periods) will be 
summarized. At the time of a clinical cutoff, TEAEs with onset date prior to or on the clinical 
cutoff date will be summarized.  
The following tabular summaries will be presented for the SS: 
• 
Ongoing AEs at EP0073 study entry. Of note, this table will not be included in the interim 
analyses. 
• 
Incidence of TEAEs during the Study - Overview  
• 
Incidence of TEAEs by 3-month time interval during the On-Treatment Period. TEAEs with 
onset date prior to or on the date of last dose of UCB0942 will be included in the summary.  
• 
Incidence of TEAEs by Period (Entire Study, Evaluation, Taper, SFU) 
• 
Incidence of Serious TEAEs  
• 
Incidence of TEAEs by Relationship 
• 
Incidence of SAEs by Relationship. Of note, this table is needed for data transparency 
reporting and will not be included in the interim analyses. 
• 
Incidence of Fatal TEAEs by Relationship. Of note, this table is needed for data transparency 
reporting and will not be included in the interim analyses. 
• 
Incidence of TEAEs by Maximum Intensity 
• 
Incidence of TEAEs leading to discontinuation (ie, drop out)   
• 
Incidence of TEAEs occurring in at least 5% of Subjects  
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09 Oct 2020 
Statistical Analysis Plan 
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EP0073 
 
 
 
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• 
Incidence of TEAEs by Dose at Onset during the On-Treatment Period. TEAEs with onset 
date prior to or on the date of last dose of UCB0942 will be included in the summary.  
• 
Incidence of Non-Serious TEAEs above the Threshold of 5% of Subjects. Of note, this table 
is needed for data transparency reporting and will not be included in the interim analyses.   
Summary tables will contain counts of subjects, percentages of subjects in parentheses and the 
number of events where applicable. A subject who has multiple events in the same SOC and PT 
will be counted only once in the subject counts but all events will be included. 
In summaries of relationship to study treatment per the investigator, the following relationships 
will be summarized: ‘Not related’, ‘Related’. Events with missing relationship will be considered 
as ‘Related’ to the last given study product for summary purposes but recorded as missing in the 
listings. 
In summaries of maximum intensity, the following intensity categories will be summarized: 
‘Mild’, ‘Moderate’, ‘Severe’. Subjects who experience the same event multiple times will be 
included in the most severe category. Events with missing intensity will be considered as 
‘Severe’ events for summary purposes but recorded as missing in the listings. 
Adverse event summaries will be ordered in alphabetically by SOC and by decreasing frequency 
for the PT within SOC. 
Change#8 
The following has been added: 
10.3.1 Subjects with potential drug-induced liver injury (PDILI) 
There are specific criteria described in the protocol Section 11.6.1 to evaluate subjects for 
potential drug-induced liver injury (PDILI). A summary of number and percent of subjects 
meeting PDILI criteria will be provided along with the subject numbers. Data collected for 
PDILI subjects will be listed.  
A summary table highlighting the potential cases of Hy’s Law will be presented. Hy’s Law is 
defined as:  
• 
AST >3xULN or ALT >3xULN and 
• 
Total Bilirubin >2xULN 
In order to meet the above criteria, a subject must experience the elevation in bilirubin and ALT 
or AST at the same visit. For example, a subject who experiences a >=2 x ULN elevation of 
bilirubin at one visit and a 3 x ULN elevation in ALT (or AST) at a subsequent visit has not 
fulfilled the Hy’s law criteria. 
Change #9 
Section 12 has been updated to the current standards. 
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Statistical Analysis Plan 
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EP0073 
 
 
 
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13.2 
Amendment 2 
Rationale for the amendment 
The primary purpose of this amendment is to update SAP because of the PSL program 
termination.  
Modifications and Changes 
Major specific changes 
Change #1  
3.2.1 Analysis periods 
Unless noted otherwise, Baseline is the EP0069 2-week Prospective Outpatient Baseline Period. 
The study is divided into 4 periods: Screening Period, Evaluation Period, Taper Period, and SFU 
Period. The following periods will be considered in the definition of efficacy and safety 
variables: 
• A 2-week Screening Period from V13 to the day before V15 of the 8-week Outpatient 
Maintenance Period of the EP0069 study. 
• Evaluation Period:  Entry Visit (EV) to Last Evaluation Period Visit (LEPV) or Early 
Discontinuation Visit (EDV) or clinical data cutoff date if the subject is ongoing and does not 
have the EDV. The EV is also V15 of EP0069. Data in EP0073 database will be used in the 
analyses when possible.  
• Taper Period: the day after LEPV or EDV to End of Taper Visit or clinical data cutoff date if 
the subject is ongoing.  
• SFU Period: The day after the End of Taper Visit to date of final contact or clinical data 
cutoff date if the subject is ongoing.  
Has been changed to: 
3.2.1 Analysis periods 
Unless noted otherwise, Baseline is the EP0069 2-week Prospective Outpatient Baseline Period. 
In this study, final contact date is referred to date of final contact with subject from Study 
Completion eCRF form.  
The study is divided into 4 periods: Screening Period, Evaluation Period, Taper Period, and SFU 
Period. The following periods will be considered in the definition of efficacy and safety 
variables: 
• A 2-week Screening Period from V13 to the day before V15 of the 8-week Outpatient 
Maintenance Period of the EP0069 study. 
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Statistical Analysis Plan 
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• Evaluation Period:  Entry Visit (EV) to Last Evaluation Period Visit (LEPV) or Early 
Discontinuation Visit (EDV) or clinical data cutoff date if the subject is ongoing and does not 
have the EDV. The EV is also V15 of EP0069. Data in EP0073 database will be used in the 
analyses when possible. If a subject does not have a Visit 21/EDV, then the date of the final 
contact will be defined as the end date of the Evaluation Period.  
• Taper Period: the day after the end date of evaluation period to End of Taper Visit or clinical 
data cutoff date if the subject is ongoing. If the end of taper period (V22) is missing, here it is 
the algorithm to impute it: 
If EDV visit is missing then last date of evaluation period will be last contact date and taper and 
SFU period start/end dates will be missing. 
Else if the last dose date is before EDV date, then we assume drug was not tapered and taper 
period start/end date will be set as missing and SFU start date will be EDV+1 and SFU end date 
will be final contact date. 
Else if V22 is missing but SFU1 visit (V23) is not missing, then the end date of taper period be 
defined as max(last dose date, V23-7 days), but if this date is before the taper period start date, 
then taper period start/end dates will be set as missing. 
Else if V23 is missing but SFU2 (V24) is not missing , the end date of taper period as min(last 
dose date, V24-30 days). 
Else taper and SFU period start/end dates will be missing. 
• SFU Period: The day after the End of Taper Visit to date of final contact or clinical data 
cutoff date if the subject is ongoing.  
Change #2  
13.2.1 Pharmacokinetic Per-Protocol Set 
The Pharmacokinetic Per-Protocol Set (PK-PPS) will consist of subjects in the FAS who 
received at least 1 dose of UCB0942 in the EP0073 study and had at least 1 PK sample, and do 
not have a major protocol deviation impacting the PK. 
Has been changed to: 
13.2.1 Pharmacokinetic Per-Protocol Set 
The Pharmacokinetic Per-Protocol Set (PK-PPS) will consist of subjects in the FAS who 
received at least 1 dose of UCB0942 in the EP0073 study and had at least 1 PK sample, and do 
not have a major protocol deviation impacting the PK for all the PK samples. PK-PPS exclusion 
should be based on the individual PK samples. Only if all PK samples are excluded, the subject 
will be excluded from the PK-PPS. 
Change #3  
9.1 Plasma concentrations 
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Statistical Analysis Plan 
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EP0073 
 
 
 
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Plasma concentrations of UCB0942, 
, and 
 will be 
determined from blood samples obtained in the study during the first year (V3, V4, V5, V6, V7, 
V8, V9).  
The individual concentrations of UCB0942, 
, and 
 will be 
listed for the FAS with blood sampling dates/times and elapsed time from last administration. 
Unless otherwise stated, measured values below the limit of quantification (BLQ) will be 
reported as LLOQ/2. 
The concentrations of UCB0942 from samples taken 1-3 hours and 10-12 hours after the most 
recent UCB0942 administration will be summarized by visit using n, mean, median, SD, 
minimum, maximum, geometric mean, and geoCV and 95% CI of the geometric mean. This 
table will be repeated for UCB0942, 
, and 
. PK samples 
taken at other timepoints will be included in the subject listing but not summarized.  
Has been changed to: 
9.1 Plasma concentrations 
Plasma concentrations of UCB0942, 
, and 
 will be 
determined from blood samples obtained in the study during the first year (V3, V4, V5, V6, V7, 
V8, V9).  
The individual concentrations of UCB0942, 
 and 
 will be 
listed for the FAS with blood sampling dates/times and elapsed time from last administration. 
Unless otherwise stated, measured values below the limit of quantification (BLQ) will be 
reported as LLOQ/2. 
 
 
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Statistical Analysis Plan                                                           Padsevonil (UCB0942)                                                                                       EP0073 
 
 
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Change #4  
The table in the section 12.1.2 was truncated and was updated to the correct one. 
PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
AST (SGOT) 
<14y 
U/L 
>180 
U/L 
>180 
≥14y 
>144 
>144 
ALT (SGPT) 
1y - <18y 
U/L 
>90 
U/L 
>90 
≥18y 
>123 
>123 
Alkaline 
Phosphatase 
<4y 
U/L 
>690 
U/L 
>690 
4y - <10y 
>834 
>834 
10y - <18y 
>1174 
>1174 
≥18y 
>432 (F) 
>933 (M) 
>432 (F) 
>933 (M) 
GGT 
<6m 
U/L 
>522 
U/L 
>522 
6m - <1y 
>279 
>279 
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                                                                                                                                                                                             09 Oct 2020 
Statistical Analysis Plan                                                           Padsevonil (UCB0942)                                                                                       EP0073 
 
 
Confidential 
Page 69 of 73 
 
 
 
 
PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
1y - <13y 
>66 
>66 
13y - <18y 
>126 
>126 
≥18y 
>255 
>255 
Total Bilirubin 
>1m 
mg/dL 
≥1.5 
umol/L 
≥25.656 
Total Protein 
2m-<1y 
g/dL 
<3.0 
>10.0 
g/L 
<30 
>100 
≥1y 
<4.3 
>10.0 
<43 
>100 
Albumin 
<1y 
g/dL 
<1.6 
>6.0 
g/L 
<16 
>60 
≥1y 
<2.4 
>7.0 
<24 
>70 
BUN 
<1y 
mg/dL 
>21 
mmol/L 
>7.497 
≥1y 
>30 
>10.71 
Urea 
<1y 
mg/dL 
>42 
mmol/L 
>7.014 
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                                                                                                                                                                                             09 Oct 2020 
Statistical Analysis Plan                                                           Padsevonil (UCB0942)                                                                                       EP0073 
 
 
Confidential 
Page 70 of 73 
 
 
 
 
PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
≥1y 
>60 
>10.02 
Creatinine 
1y - <10y 
mg/dL 
>0.9 
umol/L 
>79.56 
10y - <16y 
>1.4 
>123.76 
≥16y 
>1.6 
>141.44 
Creatinine 
Clearance* 
All 
mL/min 
<70 
mL/s 
<1.169 
Calcium 
<1y 
mg/dL 
<6.9 
>12.2 
mmol/L 
<1.725 
>3.05 
1y - <18y 
<7.4 
>11.7 
<1.85 
>2.925 
≥18y 
<7.9 >11.1 
≤1.975 
≥2.775 
Phosphorous 
<1y 
mg/dL 
<1.8 
>8.2 
mmol/L 
<0.5814 
>2.6486 
≥1y 
<1.8 
>7.4 
<0.5814 
>2.3902 
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Statistical Analysis Plan                                                           Padsevonil (UCB0942)                                                                                       EP0073 
 
 
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PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
Potassium 
<1y 
mEq/L 
<3.0 
>6.5 
mmol/L 
<3.0 
>6.5 
≥1y 
<3.0 
>5.8 
<3.0 
>5.8 
Sodium 
>1m 
mEq/L 
≤130 
≥150 
mmol/L 
≤130 
≥150 
Glucose 
>1m 
mg/dL 
<50 
>180 
mmol/L 
<2.775 
>9.99 
Total Cholesterol 
1y - <18y 
mg/dL 
>250 
mmol/L 
>6.475 
≥18y 
>300 
>7.77 
LDL (calculated) 
1y - <18y 
mg/dL 
>140 
mmol/L 
>3.626 
≥18y 
>200 
>5.18 
HDL 
≤2y 
mg/dL 
<10 
mmol/L 
<0.259 
>2y 
<20 
<0.518 
Triglycerides 
<1y 
mg/dL 
>750 
mmol/L 
>8.475 
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                                                                                                                                                                                             09 Oct 2020 
Statistical Analysis Plan                                                           Padsevonil (UCB0942)                                                                                       EP0073 
 
 
Confidential 
Page 72 of 73 
 
 
 
 
PARAMETER 
AGE RANGE 
UNIT 
(conventional) 
ABNORMALITY 
CRITERIA 
(conventional) 
UNIT 
(standard) 
ABNORMALITY 
CRITERIA 
(standard) 
≥1y 
>250 
>2.825 
Uric Acid 
<1y 
mg/dL 
>7.7 
umol/L 
>457.996 
1y - <13y 
>6.5 
>386.62 
13y - <18y 
>8.6 
>511.528 
≥18y 
>6.8 (F) 
>404.464 (F) 
>9.6 (M) 
>571.008 (M) 
Thyroxine (T4) 
<1y 
ug/dL 
≤4.3 
nmol/L 
≤55.3453 
≥18.4 
≥236.8264 
≥1y 
≤3.8 
≤48.9098 
≥13.5 
≥173.7585 
Globulin 
<1y 
g/dL 
<1.0 
g/L 
<10 
>3.8 
>38 
≥1y 
<1.2 
<12 
>4.4 
>44 
Abbreviations: ALT= alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; dL = deciliter; F=female; GGT: 
gamma-glutamyltransferase; HDL = high density lipoprotein; LDL = low density lipoprotein; L = liter; M=male; m = month (a month is defined 
as 30 days) mg = milligram; mmol = millimoles; μg = microgram; U = unit; ULN = upper limit of normal; y = years (a year is defined as 365.25 
days). 
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STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution. 
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Approval Signatures
Name:
ep0073-sap-amend-2
Version:
1. 0
Document Number:
CLIN-000162665
Title:
ep0073-sap-amend-2
Approved Date:
09 Oct 2020
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 09-Oct-2020 15:11:13 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 09-Oct-2020 20:02:03 GMT+0000
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