Clinical trial NCT02710890
Conditions: Epilepsy
Keywords: Epilepsy pediatric intravenous children Lacosamide VIMPAT® seizure
Sponsor: UCB BIOSCIENCES, Inc.
Start date: 2017-05-30; Completion date: 2019-06-28
Enrollment: 103 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
EP0060 is a multicenter, open-label study to evaluate the safety and tolerability of intravenous (iv) Lacosamide (LCM) in pediatric subjects \>= 1 month to \< 17 years of age with epilepsy.

Detailed description:

Arms: arm 1: Up to 2 age-based Cohorts with Cohort 1 including at least 40 subjects who are \>=8 to \<17 years. For Cohort 2 every attempt will be made to enroll 20 subjects \>= 4 to \< 8 years of age, 12 subjects \>= 2 to \< 4 years of age and 12 subjects \>= 1 month to \< 2 years of age. A Data Monitoring Committee (DMC) will review the safety and tolerability data for each Cohort to make the following recommendations: the progression of the current Cohort, including intravenous (iv) infusion durations to be evaluated, and progression to initiate enrollment in the next Cohort (Cohort 2).
Interventions: intervention 1: Lacosamide
Intervention descriptions: intervention 1: Pharmaceutical form: solution for infusion

Concentration: 10 mg/ml

Route of Administration: intravenous

Protocol documents:
Prot_001.pdf: 
UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 1 of 240
PROTOCOL EP0060 AMENDMENT 3
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE 
THE SAFETY AND TOLERABILITY OF INTRAVENOUS 
LACOSAMIDE IN CHILDREN (≥1 MONTH TO <17 YEARS OF 
AGE) WITH EPILEPSY
PHASE 2/3
EudraCT Number: 2014-003294-42
IND Number: 068407
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
16 Dec 2014
Not applicable
Protocol Amendment 1
21 Jul 2015
Substantial
Protocol Amendment 2
30 Nov 2016
Substantial
Protocol Amendment 3
30 Apr 2018
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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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 2 of 240
STUDY CONTACT INFORMATION
Sponsor
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Principal/Coordinating Investigator
Name:
TBD
Affiliation:
Address:
Phone:
Fax:
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES, GmbH.
Alfred-Nobel-Straβe 10
40789 Monheim am Rhein
Germany
Phone:
Mobile:
Clinical Project Manager
Name:
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Not Applicable
 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 3 of 240
Clinical Trial Biostatistician
Name:
Address:
UCB BIOSCIENCES, GmbH.
Alfred-Nobel-Straβe 10
40789 Monheim am Rhein
Germany
Phone:
Fax:
Not Applicable
Clinical Monitoring Contract Research Organization
Name:
PRA Health Sciences
Address:
4130 Park Lake Avenue, Suite 400
Raleigh, NC 27612
UNITED STATES
Phone:
+1-919-786-8200
Fax:
+1-919-786-8201
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 4 of 240
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA and Canada: +1 800 880 6949 or +1 866 890 3175
Email
Global: DS_ICT@ucb.com (for interventional clinical studies)
REDACTED COPY 
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 5 of 240
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................9 
1 
SUMMARY.....................................................................................................................11 
2 
INTRODUCTION ...........................................................................................................15 
3 
STUDY OBJECTIVE(S).................................................................................................16 
4 
STUDY VARIABLES.....................................................................................................16 
4.1 
Primary safety variables...............................................................................................16 
4.2 
Other safety variables ..................................................................................................16 
4.3 
Other pharmacokinetic variables .................................................................................17 
5 
STUDY DESIGN.............................................................................................................17 
5.1 
Study description .........................................................................................................17 
5.1.1 
Study duration per subject ...................................................................................21 
5.1.2 
Planned number of subjects and site(s) ...............................................................21 
5.1.3 
Anticipated regions and countries .......................................................................21 
5.2 
Schedule of study assessments.....................................................................................22 
5.3 
Rationale for study design and selection of dose.........................................................28 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................30 
6.1 
Inclusion criteria ..........................................................................................................30 
6.2 
Exclusion criteria .........................................................................................................31 
6.3 
Withdrawal criteria ......................................................................................................33 
6.3.1 
Potential drug-induced liver injury IMP discontinuation criteria........................34 
7 
STUDY TREATMENT(S) ..............................................................................................35 
7.1 
Description of investigational medicinal product(s)....................................................35 
7.1.1 
Lacosamide solution for infusion ........................................................................35 
7.1.2 
Lacosamide oral solution for RxL and IIL subjects transitioning to SP848........35 
7.2 
Treatment(s) to be administered ..................................................................................35 
7.2.1 
Treatment Period .................................................................................................35 
7.2.2 
Transition oral lacosamide...................................................................................37 
7.3 
Packaging.....................................................................................................................37 
7.4 
Labeling .......................................................................................................................37 
7.5 
Handling and storage requirements .............................................................................37 
7.6 
Drug accountability......................................................................................................38 
7.7 
Procedures for monitoring drug accountability ...........................................................38 
7.8 
Concomitant medication(s)/treatment(s) .....................................................................38 
7.8.1 
Permitted and prohibited concomitant treatments (medications and therapies)..38 
7.9 
Blinding........................................................................................................................39 
7.10 
Randomization and numbering of subjects..................................................................39 
8 
STUDY PROCEDURES BY VISIT ...............................................................................39 
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 6 of 240
8.1 
Screening/Baseline Period ...........................................................................................39 
8.1.1 
Visit 1a and Visit 1b (Day -7 to Day 1) Screening and/or Baseline....................39 
8.2 
Treatment Period..........................................................................................................41 
8.2.1 
Visit 2 (Day 1) .....................................................................................................41 
8.2.2 
Visit 3 (Day 2 to Day 5) ......................................................................................43 
8.3 
Unscheduled Visit........................................................................................................43 
8.4 
End-of-Study Period ....................................................................................................43 
8.4.1 
Final Visit (Day 1 to 6)/Termination Visit ..........................................................43 
8.4.2 
Telephone Contact 1 (Day 2 to Day 9)................................................................44 
8.4.3 
Transition Visit (Day 1 to Day 13)......................................................................45 
8.4.4 
Telephone Contact 2 (Day 29 to Day 37)............................................................45 
9 
ASSESSMENT OF PHARMACOKINETICS................................................................45 
10 ASSESSMENT OF SAFETY..........................................................................................46 
10.1 
Adverse events.............................................................................................................46 
10.1.1 
Definition of adverse event..................................................................................46 
10.1.2 
Procedures for reporting and recording adverse events.......................................47 
10.1.3 
Description of adverse events..............................................................................47 
10.1.4 
Follow up of adverse events ................................................................................47 
10.1.5 
Rule for repetition of an adverse event................................................................47 
10.1.6 
Pregnancy ............................................................................................................47 
10.1.7 
Suspected transmission of an infectious agent via a medicinal product..............48 
10.1.8 
Overdose of investigational medicinal product ...................................................48 
10.1.9 
Safety signal detection.........................................................................................48 
10.2 
Serious adverse events .................................................................................................49 
10.2.1 
Definition of serious adverse event .....................................................................49 
10.2.2 
Procedures for reporting serious adverse events .................................................49 
10.2.3 
Follow up of serious adverse events....................................................................50 
10.3 
Adverse events of special interest................................................................................50 
10.4 
Immediate reporting of adverse events........................................................................51 
10.5 
Anticipated serious adverse events ..............................................................................51 
10.6 
Laboratory measurements............................................................................................52 
10.6.1 
Pregnancy testing.................................................................................................53 
10.6.2 
Liver function tests and evaluation of PDILI ......................................................53 
10.6.2.1 
Consultation with Medical Monitor and local hepatologist ......................57 
10.6.2.2 
Immediate action: determination of IMP discontinuation.........................57 
10.6.2.3 
Testing: identification/exclusion of alternative etiology...........................57 
10.6.2.4 
Follow-up evaluation.................................................................................59 
10.7 
Other safety measurements..........................................................................................60 
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 7 of 240
10.7.1 
Vital signs, body weight, and height ...................................................................60 
10.7.2 
12-lead ECG ........................................................................................................60 
10.7.3 
Overall ECG interpretation..................................................................................60 
10.7.4 
Physical examination...........................................................................................60 
10.7.4.1 
Complete physical examination ................................................................60 
10.7.4.2 
Brief physical examination........................................................................60 
10.7.5 
Assessment of suicidality ....................................................................................60 
10.7.6 
Neurological examination....................................................................................61 
10.7.6.1 
Complete neurological examination..........................................................61 
10.7.6.2 
Brief neurological examination.................................................................61 
11 STUDY MANAGEMENT AND ADMINISTRATION.................................................61 
11.1 
Adherence to protocol..................................................................................................61 
11.2 
Monitoring ...................................................................................................................61 
11.2.1 
Definition of source data .....................................................................................62 
11.2.2 
Source data verification .......................................................................................62 
11.3 
Data handling...............................................................................................................62 
11.3.1 
Case Report form completion..............................................................................62 
11.3.2 
Database entry and reconciliation........................................................................63 
11.3.3 
Subject Screening and Enrollment log/Subject Identification Code list..............63 
11.4 
Termination of the study..............................................................................................63 
11.5 
Archiving and data retention........................................................................................63 
11.6 
Audit and inspection ....................................................................................................64 
11.7 
Good Clinical Practice .................................................................................................64 
12 STATISTICS ...................................................................................................................64 
12.1 
Definition of analysis sets............................................................................................64 
12.2 
General statistical considerations.................................................................................64 
12.3 
Planned pharmacokinetic analyses ..............................................................................65 
12.4 
Planned safety analyses................................................................................................65 
12.5 
Handling of protocol deviations...................................................................................65 
12.6 
Handling of dropouts or missing data..........................................................................65 
12.7 
Planned interim analysis and data monitoring.............................................................65 
12.7.1 
Definition of stopping rules.................................................................................65 
12.7.2 
Data Monitoring Committee................................................................................66 
12.8 
Determination of sample size.......................................................................................67 
13 ETHICS AND REGULATORY REQUIREMENTS......................................................67 
13.1 
Informed consent .........................................................................................................67 
13.2 
Subject identification cards..........................................................................................67 
13.3 
Institutional Review Boards and Independent Ethics Committees..............................68 
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 8 of 240
13.4 
Subject privacy.............................................................................................................68 
13.5 
Protocol amendments...................................................................................................69 
14 FINANCE, INSURANCE, AND PUBLICATION.........................................................69 
15 REFERENCES ................................................................................................................69 
16 APPENDICES .................................................................................................................71 
16.1 
Protocol Amendment 1 ................................................................................................71 
16.2 
Protocol Amendment 2 ..............................................................................................116 
16.3 
Protocol Amendment 3 ..............................................................................................201 
17 DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................239 
18 SPONSOR DECLARATION ........................................................................................240 
LIST OF TABLES
Table 5‒1: 
Schedule of study assessments.........................................................................23 
Table 5‒2: 
Timing of infusion, blood sampling, and measurement of vital signs and 
ECG on Treatment Days (Infusion Day 1 to Day 5) .......................................28 
Table 10‒1: 
Anticipated SAEs for the pediatric epilepsy population..................................51 
Table 10‒2: 
Laboratory tests................................................................................................53 
Table 10‒3: 
Required investigations and follow up for PDILI............................................55 
Table 10‒4: 
PDILI laboratory measurements......................................................................58 
Table 10‒5: 
PDILI information to be collected ...................................................................59 
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 9 of 240
LIST OF ABBREVIATIONS
AE
adverse event
AED
antiepileptic drug
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AV
atrioventricular
bid
twice daily
BP
blood pressure
CDMS
clinical data management system
CHMP
Committee for Medicinal Products for Human Use
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CRF
Case Report form
C-SSRS
Columbia-Suicide Severity Rating Scale
CV
coefficient of variation
DMC
Data Monitoring Committee
ECG
electrocardiogram
EDC
electronic data capture
EMA/EMEA
European Medicines Agency
EMU
epilepsy monitoring unit
EudraCT
European Union Drug Regulating Authorities Clinical Trials
FDA
Food and Drug Administration
GCP
Good Clinical Practice
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IIL
initiating intravenous lacosamide
IMP
investigational medicinal product
IND
Investigational New Drug
IRB
Institutional Review Board
iv
intravenous
LCM
lacosamide
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 10 of 240
LFT
liver function test
MAOI
monoamine oxidase inhibitor
OLL
open-label lacosamide
PDILI
potential drug-induced liver injury
PK
pharmacokinetic(s)
PK-PPS
Pharmacokinetic-Per Protocol Set
PS
Patient Safety
QTc
corrected QT interval
RxL
prescribed lacosamide (eg, VIMPAT)
SAE
serious adverse event
SD
standard deviation
SOP
Standard Operating Procedure
SS
Safety Set
ULN
upper limit of normal
VNS
vagus nerve stimulation
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 11 of 240
1
SUMMARY
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of 
intravenous (iv) lacosamide (LCM; VIMPAT®) infusions in pediatric subjects ≥1 month to <17 
years of age with epilepsy. 
EP0060 will include approximately 100 subjects. The following subjects will be eligible for 
enrollment in EP0060:
x Open-label LCM (OLL) subjects: currently receiving oral LCM as adjunctive or 
monotherapy as participants in an open-label long-term study (SP848, EP0034, or other 
pediatric study).
x Prescribed-LCM (RxL) subjects: currently receiving prescribed oral LCM from 
commercial supply (eg, VIMPAT) as adjunctive or monotherapy.
x Initiating iv LCM (IIL) subjects: not currently receiving LCM and will receive iv LCM as 
adjunctive treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL 
subjects.
Subjects can receive iv LCM as follows: 
x Replacement for oral LCM treatment (OLL and RxL subjects): 
 Clinical need administration: Subjects currently taking prescribed oral LCM (or any 
enteric LCM administration, eg, LCM administration by feeding tube) who need to 
undergo a procedure and are treated at an epilepsy monitoring unit (EMU) or health 
care facility, or other situations where iv administration is clinically appropriate and 
oral administration is not feasible (ie, surgery). In these subjects, the maximum 
number of iv doses of LCM is 10. 
 Elective administration: Subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) and elect to receive iv LCM 
administration at an EMU or healthcare facility. In these subjects, the maximum 
number of iv doses of LCM is 2.
x Adjunctive iv LCM treatment initiation (IIL subjects):
 Clinical need administration: Subjects not currently taking LCM who need to undergo 
a procedure, be treated at an EMU or health care facility, or other situations where iv 
administration is clinically appropriate and oral administration is not feasible (ie, 
surgery). In these subjects, the maximum number of iv doses of LCM is 10.
 Elective administration: Subjects not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
Pediatric subjects entering into EP0060 from the OLL group will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll into 
EP0060 from the RxL group will temporarily switch from their prescribed oral LCM treatment to 
the iv LCM formulation. Subjects in the IIL group will initiate adjunctive treatment with iv 
LCM. After completion of this study, eligible subjects from the RxL and IIL groups will have the 
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 12 of 240
option to continue LCM treatment in SP848. Subjects will be enrolled from approximately 40 
sites in North America, Europe, and Asia. Additional sites or regions may be added if deemed 
necessary.
The primary objective of EP0060 is to evaluate the safety and tolerability of iv LCM infusion(s) 
in pediatric subjects ≥1 month to <17 years with epilepsy. EP0060 is planned to include up to 
2 age-based cohorts with Cohort 1 including at least 40 subjects who are ≥8 to <17 years and 
Cohort 2 including approximately 44 subjects who are ≥1 month to <8 years. Within Cohort 1, at 
least 20 subjects will be ≥12 to <17 years of age and at least 20 subjects will be ≥8 to <12 years 
of age. Within Cohort 2, every attempt will be made to enroll 20 subjects ≥4 to <8 years of age, 
12 subjects ≥2 to <4 years of age, and 12 subjects ≥1 month to <2 years of age.
A Data Monitoring Committee (DMC) will review the safety and tolerability data for each 
cohort to make the following recommendations: the progression of the current cohort, including 
iv infusion durations to be evaluated, and progression to initiate enrollment in the next cohort 
(Cohort 2). 
EP0060 is comprised of the following study periods: 
x For all subjects:
 Screening and/or Baseline Period (up to 7 days),
 Treatment Period
(1) Clinical need administration: up to 10 doses or up to 5 days
(2) Elective administration: up to 2 consecutive doses over approximately 24 hours
 End-of-Study/Final Visit (1 day), 
 End-of-Study/Telephone Contact 1 (1 to 3 days),
x 
Additional visits or contacts as follows:
 RxL and IIL subjects who are eligible and choose to continue oral LCM treatment for 
up to 2 years in SP848
◦ 
Transition Visit, which can be concurrent with Final Visit or separate (up to 
7 days after Final Visit)
 RxL and IIL subjects who do not continue LCM treatment in SP848
◦ 
End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM). 
For all subjects, the Screening, Baseline, Treatment Period, and Final Visit may occur in 1 day, 
provided the subject only requires 1 iv infusion, results of examinations (ie, 12-lead 
electrocardiogram [ECG], laboratory measurements) are available to allow verification of subject 
eligibility prior to infusion, and time permits for completion of Final Visit assessments. 
If further time is required for Screening assessments or to obtain results, the Screening Period 
can last up to 7 days. For OLL and RxL subjects, oral LCM will be administered during this time 
from their open-label study or prescribed LCM supply in accordance with each subject’s oral 
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 13 of 240
LCM dosage regimen. For IIL subjects, no LCM will be administered during the Screening 
Period.
During the Treatment Period, at least 1 dose of iv LCM will be administered. If more than 
1 infusion is given, infusions will occur twice daily (bid) at approximately 12-hour intervals for 
up to 10 doses (or up to 5 days for clinical need administration or up to 2 consecutive doses [over 
approximately 24 hours]) for elective administration. For OLL and RxL subjects, the daily dose 
of iv LCM will be the same as the subject's current stable daily dose of oral LCM (2 to 
12mg/kg/day or 100 to 600mg/day). The maximum dose permitted in this study for OLL and 
RxL subjects is 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, the iv LCM 
dose will be 1mg/kg bid (subjects weighing <50kg) or 50mg bid (subjects weighing ≥50kg). The 
total LCM daily dose for IIL subjects should be 2mg/kg/day (subjects weighing <50kg) or 
100mg/day (subjects weighing ≥50kg) and should remain constant for at least 7 days prior to a 
LCM dose increase. 
During the Treatment Period, blood samples will be obtained for pharmacokinetic (PK) analysis, 
and detailed safety assessments will be performed. 
The timing of the End-of-Study/Final Visit will depend on the timing of the last LCM infusion 
and available time to complete all assessments. The Final Visit can be conducted on the same 
day as the last dose of iv LCM if time permits to complete all assessments. Otherwise, the Final 
Visit should be conducted the day following the last dose of iv LCM. The safety follow-up
Telephone Contact 1 should occur 1 to 3 days after the Final Visit for all subjects. 
For RxL and IIL subjects who are eligible and choose to continue LCM treatment in SP848, a 
Transition Visit will be conducted either concurrent with the Final Visit or separately. Oral LCM 
solution will be provided for these subjects to allow continuity of LCM therapy after the final 
LCM infusion and the subject’s Transition Visit in EP0060 and Visit 1 for SP848.
For RxL and IIL subjects who will not continue LCM treatment in SP848, an additional safety 
follow-up Telephone Contact 2 should occur 30 days (±2 days) after the last iv dose of study 
LCM treatment.
The maximum study durations are as follows:
x Approximately 16 days:
 Subjects in the OLL group will resume participation in their respective study and 
either resume oral LCM treatment or follow taper regimen as described in the long-
term, open-label study accordingly.
x Approximately 23 days
 Subjects in the RxL or IIL groups who, if determined clinically appropriate, are given 
the option to continue oral LCM treatment in SP848.
x Approximately 45 days:
 Subjects in the RxL or IIL groups who will not continue oral LCM treatment in 
SP848. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 14 of 240
Subjects should continue antiepileptic drug (AED) treatment at the discretion of the treating 
physician. For RxL subjects who will discontinue use of LCM, the subject should complete the 
EP0060 Final Visit and taper at the discretion of the treating physician.
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes. 
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes,
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to receive 
iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a duration of 
30 minutes but no longer than 60 minutes whenever possible.
After completion of the first 20 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of
30 minutes but no longer than 60 minutes. 
x OR approximately 30 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes. 
x OR Cohort 2 should be stopped. 
This design will result in a total exposure of approximately 100 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. A completer for this study is 
defined as a subject who completes at least 1 visit with iv LCM treatment and the associated
assessments for that visit (eg, PK samples, vital signs, 12-lead ECG).
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 15 of 240
2
INTRODUCTION
Epilepsy is the second most prevalent neurological disorder in the world. It is estimated that 
almost 70 million people suffer from epilepsy (Ngugi et al, 2011). Although some forms of 
epilepsy may respond to surgical treatment and others may not require any treatment at all, most 
patients with epilepsy require appropriate pharmacological therapy (Perucca, 1996). The Institute 
of Medicine of the National Academies recently provided a review of the burdens of epilepsy, 
global incidence and prevalence of epilepsy, classification systems for seizure types and 
syndromes, gaps in information about epilepsy, and general recommendations (Institute of 
Medicine, 2012). In the past 2 decades, several new options for the medical treatment of epilepsy 
have been introduced, including novel AEDs and vagus nerve stimulation (VNS).
The classification of seizures and epilepsy syndromes in children was described in 1989 by the 
Commission on Classification and Terminology of the International League Against Epilepsy 
(1989; Aicardi, 1994). Seizures are categorized based on whether the onset is focal or 
generalized and whether the disorder is idiopathic, symptomatic, or cryptogenic. Specific 
syndromes are further classified according to a number of criteria, including seizure type, cause, 
anatomy, precipitating factors, age at onset, and sometimes prognosis.
The newer AEDs differ from older agents in several important ways, including mechanism of
action, spectrum of activity, and PK characteristics (Herman and Pedley, 1998). However, more 
than 30% of patients have inadequate seizure control on currently available AEDs or experience 
significant adverse drug effects (CHMP/EWP/566/98, 2010).
Among the newer AEDs, only 6 (gabapentin, lamotrigine, oxcarbazepine, topiramate, 
levetiracetam, and perampanel) have successfully demonstrated efficacy as adjunctive therapy in 
children with difficult-to-treat partial-onset seizures (Rheims and Ryvlin, 2013; Glauser et al, 
2006; Appleton et al, 1999; Duchowny et al, 1999; Elterman et al, 1999). Despite the availability 
of new AEDs, more than 25% of pediatric patients have inadequate seizure control on currently 
available AEDs, or experience significant adverse drug effects (Hadjiloizou and Bourgeois, 
2007). Therefore, a need remains for AEDs with improved effectiveness and tolerability 
(Shorvon, 2009).
Intravenous formulations are particularly helpful as short-term replacement of oral formulations 
for patients unable to take oral products (eg, preoperative and postoperative patients, patients 
with acute gastrointestinal disorders). Such formulations allow patients to be maintained on the 
same AED on their stable dose when they are unable to take the drug orally. Intravenous 
formulations may also be helpful in the initiation of treatment in certain situations when the 
patient is unable to take oral medications.
In the US, oral tablets and oral solution (syrup) of LCM are indicated for the treatment of partial-
onset seizures in patients 4 years of age and older. As the safety of LCM injection for iv use has 
not been established in pediatric patients, LCM injection for iv use at infusion durations of 15 to 
60 minutes is indicated for the treatment of partial-onset seizures only in patients 17 years of age 
and older as an alternative when oral administration is temporarily not feasible. 
Additionally, LCM has been approved in the EU (oral tablets, oral solution [syrup], and solution 
for iv infusion), as monotherapy and adjunctive therapy in the treatment of partial-onset seizures 
with or without secondary generalization in patients 4 years of age and older. The iv formulation 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 16 of 240
at infusion durations of 15 to 60 minutes is approved as an alternative for patients when oral 
administration is temporarily not feasible.
Recently, a retrospective evaluation was conducted to examine the use of iv LCM in 47 infants 
and children from 4 months to <12 years of age (Arkilo et al, 2016). The median age across the 
47 children was 6.5 years, and 18 children were <3 years of age. Intravenous LCM was 
administered as adjunctive treatment along with ≥2 other AED. Lacosamide dose levels ranged 
from 1 to 11mg/kg, and the infusion was given over 30 minutes. Fifteen of the children were 
administered iv LCM either as replacement treatment for oral maintenance dose (n=10) or to 
initiate maintenance dose (n=5). For the remaining children, iv LCM was used to treat acute 
exacerbation of seizure frequency (n=18), status epilepticus (n=11) or epilepsia partialis continua 
(n=3). Children were observed for at least 48 hours after infusion. The 11 children with status 
epilepticus were not able to respond to inquiries about adverse effects. Of the remaining 
36 subjects, 5 experienced adverse effect of sedation which resolved in all 5 within 24 hours. No 
other observable adverse effects were noted. No cardiac events were noted during the infusions 
for the 80% of children who had ECG evaluation during the infusion. This study shows an initial 
positive benefit-risk profile for the use of iv LCM in infants and children from 4 months to 
<12 years of age. 
The results of EP0060 will provide safety, tolerability, and PK data regarding the use of the 
iv LCM formulation either as replacement for oral LCM or for adjunctive LCM treatment 
initiation in pediatric subjects ≥1 month to <17 years with epilepsy.
3
STUDY OBJECTIVE(S)
The primary objective of this study is to evaluate the safety and tolerability of iv LCM 
infusion(s) in pediatric subjects ≥1 month to <17 years with epilepsy. An additional objective is 
to evaluate the PK of iv LCM in pediatric subjects with epilepsy. 
4
STUDY VARIABLES
4.1
Primary safety variables
Safety and tolerability will be assessed using the following primary variables:
x Adverse events (AEs) reported spontaneously by the subject and/or caregiver (including 
parent/legal guardian) or observed by the investigator
x Subject withdrawals due to AEs
4.2
Other safety variables
Other safety variables include the following:
x Changes in 12-lead electrocardiograms (ECGs)
x Changes in vital sign measurements (blood pressure [BP] and pulse rate)
x Changes in physical examinations
x Changes in neurological examinations
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 17 of 240
4.3
Other pharmacokinetic variables
Other PK variables will include plasma concentration of LCM and its main metabolite,
SPM 12809.
5
STUDY DESIGN
5.1
Study description
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of iv 
LCM infusions in pediatric subjects ≥1 month to <17 years of age with epilepsy. EP0060 will 
include approximately 100 subjects. The following subjects will be eligible for enrollment in 
EP0060:
x OLL subjects: currently receiving oral LCM as adjunctive or monotherapy as participants 
in an open-label long-term study (SP848, EP0034, or other pediatric study).
x RxL subjects: currently receiving prescribed oral LCM from commercial supply (eg, 
VIMPAT) as adjunctive or monotherapy.
x IIL subjects: not currently receiving LCM and will receive iv LCM as adjunctive 
treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL subjects.
Subjects can receive iv LCM as follows:
x Replacement for oral LCM treatment (OLL and RxL subjects): 
 Clinical need administration: subjects currently taking prescribed oral LCM (or any 
enteric LCM administration, eg, LCM administration by feeding tube) who need to 
undergo a procedure and are treated at an EMU or health care facility, or other 
situations where iv administration is clinically appropriate and oral administration is 
not feasible (ie, surgery). In these subjects, the maximum number of iv doses of LCM 
is 10.
 Elective administration: subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) and elect to receive iv LCM 
administration at an EMU or healthcare facility. In these subjects, the maximum 
number of iv doses of LCM is 2. 
x Adjunctive iv LCM treatment initiation (IIL subjects):
 Clinical need administration: subjects not currently taking LCM who need to undergo 
a procedure, be treated at an EMU or health care facility, or other situations where iv 
administration is clinically appropriate and oral administration is not feasible (ie, 
surgery). In these subjects, the maximum number of iv doses of LCM is 10.
 Elective administration: subjects not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
Pediatric subjects entering into EP0060 from the OLL group will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll into 
EP0060 from the RxL group will temporarily switch from their prescribed oral LCM treatment to 
the iv LCM formulation while subjects in the IIL group will initiate adjunctive treatment with iv 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 18 of 240
LCM. After completion of this study, eligible subjects from the RxL and IIL groups will have the 
option to continue LCM treatment in SP848. Subjects will be enrolled from approximately 40 
sites in North America, Europe, and Asia. Additional sites or regions may be added if deemed 
necessary.
EP0060 is planned to include up to 2 age-based cohorts with Cohort 1 including at least 
40 subjects who are ≥8 to <17 years and Cohort 2 including approximately 44 subjects who are 
≥1 month to <8 years. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age and 
at least 20 subjects will be ≥8 to <12 years of age. Within Cohort 2, every attempt will be made 
to enroll 20 subjects ≥4 to <8 years of age, 12 subjects ≥2 to <4 years of age, and 12 subjects ≥1 
month to <2 years of age. 
A DMC will review the safety and tolerability data for each cohort to make the following 
recommendations: the progression of the current cohort, including iv infusion durations to be 
evaluated, and progression to initiate enrollment in the next cohort (Cohort 2). Details regarding 
the DMC are provided in Section 12.7.2.
EP0060 is comprised of the following study periods: 
x For all subjects:
 Screening and/or Baseline Period (up to 7 days),
 Treatment Period
(1) Clinical need administration (see above in this Section): up to 10 doses or up to 5 
days
(2) Elective administration (see above in this Section): up to 2 consecutive doses over 
approximately 24 hours
 End-of-Study/Final Visit (1 day), 
 End-of-Study/Telephone Contact 1 (1 to 3 days),
x 
Additional visits or contacts as follows:
 RxL and IIL subjects who are eligible and choose to continue oral LCM treatment for 
up to 2 years in SP848
◦ 
Transition Visit, which can be concurrent with Final Visit or separate (up to 7 
days after Final Visit)
 RxL and IIL subjects who do not continue LCM treatment in SP848
◦ 
End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM).
For all subjects, the Screening, Baseline, Treatment Period, and Final Visit may occur in 1 day, 
provided the subject only requires 1 iv infusion, results of examinations (ie, ECG, laboratory 
measurements) are available to allow verification of subject eligibility prior to infusion, and time 
permits for completion of Final Visit assessments. 
If further time is required for Screening assessments or to obtain results, the Screening Period 
can last up to 7 days. For OLL and RxL subjects, oral LCM will be administered during this time 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 19 of 240
from their open-label study or prescribed LCM supply in accordance with each subject’s oral 
LCM dosage regimen. For IIL subjects, no LCM will be administered during the Screening 
Period.
During the Treatment Period, at least 1 dose of iv LCM will be administered. If more than 
1 infusion is given, infusions will occur twice daily (bid) at approximately 12-hour intervals for 
up to 10 doses (or up to 5 days) for clinical need administration or up to 2 consecutive doses 
(over approximately 24 hours) for elective administration. For OLL and RxL subjects, the daily 
dose of iv LCM will be the same as the subject's current stable daily dose of oral LCM (2 to 
12mg/kg/day or 100 to 600mg/day). The maximum dose permitted in this study for OLL and 
RxL subjects is 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, the iv LCM 
dose will be 1mg/kg bid (subjects weighing <50kg) or 50mg bid (subjects weighing ≥50kg). The 
total LCM daily dose for IIL subjects should be 2mg/kg/day (subjects weighing <50kg) or 
100mg/day (subjects weighing ≥50kg) and should remain constant for at least 7 days prior to a 
LCM dose increase. 
During the Treatment Period, blood samples will be obtained for PK analysis, and safety 
assessments will be performed (AEs, physical and neurological exams, pulse rate, BP, 12-lead 
ECG, clinical hematology and chemistry, and Columbia-Suicide Severity Rating Scale [C-SSRS] 
when applicable). 
The timing of the End-of-Study/Final Visit will depend on the timing of the last LCM infusion
and available time to complete all assessments. The Final Visit can be conducted on the same 
day as the last dose of iv LCM if time permits to complete all assessments. Otherwise, the Final 
Visit should be conducted the day following the last dose of iv LCM. The safety follow-up
Telephone Contact 1 should occur 1 to 3 days after the Final Visit for all subjects. 
For RxL and IIL subjects who are eligible and choose to continue LCM treatment in SP848, a 
Transition Visit will be conducted either concurrent with the Final Visit or separately. Oral LCM 
solution will be provided for these subjects to allow continuity of LCM therapy after the final 
LCM infusion and the subject’s Transition Visit in EP0060 and Visit 1 for SP848. 
For RxL and IIL subjects who will not continue LCM treatment in SP848, an additional safety 
follow-up Telephone Contact 2 should occur 30 days (±2 days) after the last iv dose of study 
LCM treatment.
The maximum study durations are as follows:
x Approximately 16 days:
 Subjects in the OLL group will resume participation in their respective study and 
either resume oral LCM treatment or follow taper regimen as described in the long-
term, open-label study accordingly.
x Approximately 23 days
 Subjects in the RxL or IIL groups who, if determined clinically appropriate, are given 
the option to continue oral LCM treatment in SP848.
x Approximately 45 days:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 20 of 240
 Subjects in the RxL or IIL groups who will not continue oral LCM treatment in 
SP848. 
Subjects should continue AED treatment at the discretion of the treating physician. For RxL
subjects who directly enrolled and will discontinue use of LCM, the subject should complete the 
EP0060 Final Visit and taper at the discretion of the treating physician.
The schedule of study assessments is provided in Section 5.2.
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes.
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to receive 
iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a duration of 
30 minutes but no longer than 60 minutes whenever possible.
After completion of the first 20 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes.
x OR approximately 30 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR Cohort 2 should be stopped. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 21 of 240
This design will result in a total exposure of approximately 100 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. A completer for this study is 
defined as a subject who completes at least 1 visit with iv LCM treatment and the associated 
assessments for that visit (eg, PK samples, vital signs, 12-lead ECG).
5.1.1
Study duration per subject
For clinical need administration, the planned maximum iv LCM exposure will be up to 10 doses 
(or up to 5 days). For elective administration, the planned maximum iv LCM exposure will be up 
to 2 consecutive doses (over approximately 24 hours). 
For OLL subjects, the planned maximum total study duration assuming clinical need 
administration will be approximately 16 days (up to 7 days for screening, up to 5 days of 
treatment, 1 day for discharge/Final Visit, and a safety follow-up Telephone Contact 1 at 1 to 3 
days after the Final Visit). 
For RxL and IIL subjects who will continue LCM treatment in SP848, the planned maximum 
total study duration assuming clinical need administration will be approximately 23 days to 
allow arrangement for assessments to transition to SP848 (up to 7 days for screening, up to 
5 days of treatment, 1 day for discharge/Final Visit, safety follow-up Telephone Contact 1 at 1 to 
3 days after the Final Visit, and the Transition Visit at 1 to 7 days after the last dose). The Final 
Visit and the Transition Visit may occur on the same day or separate days, depending on 
availability and scheduling.
For RxL and IIL subjects who will not continue LCM treatment in SP848, the planned maximum 
total study duration (assumes clinical need administration) will be approximately 45 days to 
allow for further safety follow-up (up to 7 days for screening, up to 5 days of treatment, 1 day for
discharge/Final Visit, safety follow-up Telephone Contact 1 at 1 to 2 days after the Final Visit, 
and safety follow-up Telephone Contact 2 at 30 days [±2 days] after the last dose).
For those subjects electively receiving iv LCM, the above maximum total study durations are 
reduced by 4 days. 
The end of the study is defined as the date of the last contact of the last subject in the study.
5.1.2
Planned number of subjects and site(s)
Approximately 100 subjects will be enrolled at approximately 40 sites.
The following cohorts are planned:
x Cohort 1: at least 40 subjects from ≥8 to <17 years of age, with at least 20 subjects from 
≥12 to <17 years of age and at least 20 subjects from ≥8 to <12 years of age
x Cohort 2: every attempt will be made to enroll 20 subjects ≥4 to <8 years of age, 12 
subjects ≥2 to <4 years of age, and 12 subjects ≥1 month to <2 years of age.
The remaining subjects may be enrolled in either of the 2 cohorts.
5.1.3
Anticipated regions and countries
The study will be conducted at selected sites from North America, Europe, and Asia. Additional 
sites or regions may be added as deemed necessary.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 22 of 240
5.2
Schedule of study assessments
The schedule of study assessments is provided in Table 5‒1, and timing of infusion, blood 
sampling, and measurement of vital signs and ECG on treatment days is provided in
Table 5‒2.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 23 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitd
End-of-Study Period
Visit
V1aa
V1bb
V2
V3c
Final 
Visite
TC1f
Transition 
Visitg
TC2h
Study Day
-7 to 
1
-1 to 
1
1
2 to 5
1 to 6
2 to 9
1 to 13
29 to 
37
Written informed consent
X
Inclusion/exclusion criteria
X
Xi
Demographics
X
Medical procedures
X
X
X
X
X
X
X
X
Procedure historyj
X
Medical history/updatej
X
X
Diagnosis of epilepsyj
X
Seizure historyk
X
Childbearing potentialj
X
LCM dosing historyl
X
X
LCM dosing information since 
Treatment Period
X
X
X
Prior and concomitant medicationsm
X
X
X
X
X
X
X
X
X
Concomitant AEDs/VNS settings/ 
ketogenic diet 
X
X
X
X
X
X
Xn
Xn
Urine pregnancy testing (as 
applicable)
X
X
X
Withdrawal criteria
X
X
X
X
X
X
AE reporting
X
X
X
X
X
X
X
X
X
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 24 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitd
End-of-Study Period
Visit
V1aa
V1bb
V2
V3c
Final 
Visite
TC1f
Transition 
Visitg
TC2h
Study Day
-7 to 
1
-1 to 
1
1
2 to 5
1 to 6
2 to 9
1 to 13
29 to 
37
Physical examination (complete)
X
X
Physical examination (brief)
X
Xo
Xo
X
Neurological examination 
(complete)
X
X
Neurological examination (brief)
X
Xo
Xo
X
Clinical chemistry and 
hematologyp,q
X
Xr
X
12-lead ECG
X
X
Xs
Xs
X
Vital signs
X
X
Xt
Xt
X
X
Body weight and height
X
PK blood sampling
Xu
Xv
Intravenous LCM infusionw
X
X
C-SSRSx
X
Xy
Xo
Xo
Xd
X
Additional items for RxL and IIL subjects continuing into SP848
Dispense transitional supply of 
oral LCM solutiong
Xz
Collect transitional supply of 
oral LCM solution
X
Visit 1 SP848 assessments 
(documented in SP848) 
X
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; C-SSRS=Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; IIL=initiating iv 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 25 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitd
End-of-Study Period
Visit
V1aa
V1bb
V2
V3c
Final 
Visite
TC1f
Transition 
Visitg
TC2h
Study Day
-7 to 
1
-1 to 
1
1
2 to 5
1 to 6
2 to 9
1 to 13
29 to 
37
LCM; iv=intravenous; LCM=lacosamide; OLL=open-label LCM; PK=pharmacokinetics; RxL=prescribed commercial LCM; TC=Telephone Contact; V=Visit; 
VNS=vagus nerve stimulation
a
The Screening and/or Baseline Visit can occur on the same day as the first iv LCM infusion, if necessary. In this case, it is required that all Screening 
procedures are performed and the results of examinations (ie, ECG, laboratory measurements) are available to allow verification of subject eligibility.
b
Visit 1b only applies when Screening and Baseline occur on separate days. 
c
If iv LCM treatment is continued after Day 1, assessments for Visit 3 (excluding PK blood sampling [see footnote v]) must be completed for each infusion 
of iv LCM treatment in EP0060, unless otherwise noted (see footnote o).  
d
If an Unscheduled Visit is needed, the assessments noted will be performed. Additional assessments can be performed at the investigator’s discretion. If the 
Unscheduled Visit is due to an AE, the C-SSRS assessment should be completed and collection of a blood sample for LCM PK analysis is at the discretion 
of the investigator.
e
A Final Visit must be completed for all subjects who complete or withdraw prematurely from EP0060. The Final Visit may occur on the same day as the last 
dose of iv LCM, time permitting. Otherwise, the Final Visit should occur on the following day. For subjects who will discontinue use of LCM, the subject 
should complete the EP0060 Final Visit and either refer to the long-term, open-label studies taper regimen for OLL subjects or taper at the discretion of the 
treating physician for RxL subjects.
f
The Telephone Contact 1 Visit assessment should be performed 1 to 3 days after the Final Visit. During the contact, the site should inquire as to whether the 
subject noted any change at the site of the infusion.
g
The Transition Visit will only be conducted for RxL and IIL subjects who will continue LCM treatment in SP848. This visit can occur at the same time as 
the Final Visit or on another day up to and including 7 days after the Final Visit and should occur at the same time as Visit 1 for SP848. 
h
The Telephone Contact 2 Visit will only be conducted for RxL and IIL subjects who will not continue LCM treatment in SP848.
i
Verification that the subject continues to meet inclusion/exclusion criteria if Screening and Baseline occur on separate days.
j
Procedure history, medical history, diagnosis of epilepsy, and childbearing potential will be collected for RxL and IIL subjects at Screening. For OLL 
subjects, a medical history update will be captured in the previous long-term open-label study and not in EP0060. 
k
Subject or caregiver (including parent/legal guardian) will be asked how many seizures the subject has had over the past 4 weeks as a historical baseline for 
RxL and IIL subjects.
l
For OLL and RxL subjects, LCM dosing history will include date, time, and dosage information during the last 3 days.
m
Prior medications will only be collected for direct-enroll subjects. 
n
At Telephone Contact follow-up calls, only concomitant AED and ketogenic diet information will be gathered (ie, settings for VNS will not be gathered).
o
During the Treatment Period, brief physical examination, brief neurological examination, and C-SSRS should be performed once per day and after an 
infusion.
p
Screening laboratory assessments may be conducted up to and including the day of the infusion provided they are reviewed and meet inclusion/exclusion 
criteria prior to the infusion. For all subjects, local laboratory results obtained for routine diagnostic and medical care can be used whenever possible if 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 26 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitd
End-of-Study Period
Visit
V1aa
V1bb
V2
V3c
Final 
Visite
TC1f
Transition 
Visitg
TC2h
Study Day
-7 to 
1
-1 to 
1
1
2 to 5
1 to 6
2 to 9
1 to 13
29 to 
37
collected no more than 24 hours prior to Screening/Baseline Visit in order to minimize blood loss associated with the study. Use of the central or local 
laboratory is at the discretion of the investigator for all visits except the Final Visit. The central laboratory must be used for laboratory samples collected at 
the Final Visit.
q
Bicarbonate testing is optional for subjects weighing less than 8kg. Consider testing for bicarbonate in subjects weighing less than 8kg in cases of suspected 
metabolic disturbances such as metabolic acidosis.
r
If Screening and Baseline Visits are not performed on the same day, repetition of laboratory assessments at Baseline is at the discretion of the investigator.
s
A 12-lead ECG will be performed approximately 20 minutes prior to each infusion and at approximately 15, 30, 60 minutes, and 2 hours from the start of 
each iv administration. Care should be taken to assure proper lead placement and quality ECG recordings. Subjects should be at rest (sitting or supine) at 
least 3 minutes prior to each ECG recording and should be motionless during the recording, when feasible.
t
Vital signs will be performed approximately 10 minutes prior to each infusion and at approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of 
each iv administration. Noninvasive BP (systolic and diastolic) and pulse rate will be measured at study visits after at least 3 minutes at rest, when feasible.
u
Plasma samples will be obtained from a different region of the body from the region in which the solution for infusion was administered for the first iv LCM 
infusion (Day 1): predose for OLL and RxL subjects (within 1 hour prior to iv LCM infusion) and postdose for all subjects (within 1 to 4 hours after end of 
iv LCM infusion). If the postdose PK sample is taken at a similar time for ECG and vital signs (ie, the 2 hour time point), the PK sample will be drawn after 
ECG and vital signs have been taken. Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in the event of a 
relevant treatment-emergent AE.
v
If the subject has more than 1 iv LCM infusion, it is optional to also collect plasma samples for the final iv LCM infusion (Day 2 to 5/Early Termination): 
predose for all subjects (within 1 hour prior to iv LCM infusion) and postdose for all subjects (within 1 to 4 hours after end of iv LCM infusion). If the 
postdose PK sample is taken at a similar time for ECG and vital signs (ie, the 2 hour time point), the PK sample will be drawn after ECG and vital signs 
have been taken. Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in the event of a relevant 
treatment-emergent AE.
w
During the Treatment Period subjects will receive at least 1 dose of iv LCM. If more than 1 infusion is needed, infusions will occur bid at approximately 
12-hour intervals up to either 2 doses (elective administration) or 10 doses (clinical need administration). 
x
All subjects ≥6 years of age will complete the “Baseline/Screening” version of the C-SSRS at Visit 1 and will complete the “Since Last Visit” version at 
subsequent visits. If a subject becomes 6 years of age during the study, the "Already Enrolled" version of the C-SSRS should be used at the first visit at 
which the subject is 6 years of age and the “Since Last Visit” version used at subsequent visits. If the subject is <6 years of age, assessment for signs of 
depression will be conducted as described in Section 10.7.5 of the protocol.
y
The C-SSRS assessment does not need to be completed twice if Screening/Baseline assessments are done on the same day. If Screening/Baseline and Visit 2 
occur on the same day, 2 assessments should be completed with 1 predose and 1 after infusion.
z
For RxL and IIL subjects who are eligible and wish to enroll in SP848, a short-term oral LCM solution will be dispensed to allow continuity of LCM 
treatment while visits and assessments are scheduled for starting SP848. Subjects (or their caregivers) will administer the oral LCM solution twice a day,
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 27 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitd
End-of-Study Period
Visit
V1aa
V1bb
V2
V3c
Final 
Visite
TC1f
Transition 
Visitg
TC2h
Study Day
-7 to 
1
-1 to 
1
1
2 to 5
1 to 6
2 to 9
1 to 13
29 to 
37
starting approximately 12 hours after the final iv LCM infusion, according to the investigator’s instructions until the subject returns for the Transition Visit.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 28 of 240
Table 5‒2:
Timing of infusion, blood sampling, and measurement of vital signs 
and ECG on Treatment Days (Infusion Day 1 to Day 5)
Approximate time points in relation 
to iv LCM infusion  
Vital signsa
12-lead ECGb
PK blood samplingc
-59min to -3min
Xd
-20min (±10 min)
X
-10min (±5 min)
X
T0 (start of infusion)
+5min (±2 min)
X
+10min (±2 min)
X
+15min (±5 min)
X
+20min (±5 min)
X
+30min (±5 min)
X
+45min (±5 min)
X
+60min (±10 min)
X
X
+1h to +4he
X
+2h (±15 min)
X
X
AE=adverse event; BP=blood pressure; ECG=electrocardiogram; h=hours; iv=intravenous; LCM=lacosamide; 
min=minutes; PK=pharmacokinetics; T=time
a Noninvasive BP (systolic and diastolic) and pulse rate will be measured after at least 3 minutes at rest, when 
feasible, at the indicated approximate time points before and after the start of each iv LCM infusion.
b A 12-lead ECG will be performed at the indicated approximate time points before and after the start of each iv 
LCM infusion. Care should be taken to assure proper lead placement and quality ECG recordings. Subjects should 
be at rest (sitting or supine) at least 3 minutes prior to each ECG recording and should be motionless during the 
recording, when feasible.
c If the postdose PK sample is taken at a similar time for ECG and vital signs (ie, the 2 hour time point), the PK 
sample will be drawn after ECG and vital signs have been taken. Plasma samples will be obtained a different 
region of the body from the region in which the solution for infusion was administered for the first iv LCM 
infusion (Day 1). If the subject has more than 1 iv LCM infusion, it is optional to also collect plasma samples for 
the final iv LCM infusion (Day 2 to 5/Early Termination), predose and postdose, at the time points indicated in the 
table. Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in the 
event of a relevant treatment-emergent AE. Depending on the target duration defined for the cohort and subject 
tolerability, end of infusion can be at 15, 30, or 60 minutes, or whenever the infusion is stopped (if prematurely 
terminated).
d For the first LCM infusion, the predose PK sample is required for OLL and RxL subjects and not required for IIL 
subjects. For optional PK sample collection of a subsequent LCM infusion, the predose sample should be collected 
from all subjects.
e Time points are in reference to T0 (start of infusion) except the postdose PK sample, which should be obtained 
within 1 to 4 hours after the end of the iv LCM infusion.
5.3
Rationale for study design and selection of dose
EP0060 is an open-label, multicenter study to investigate the safety and tolerability of iv LCM in 
pediatric subjects with epilepsy aged ≥1 month to <17 years. The results of EP0060 will provide 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 29 of 240
safety and PK data regarding the use of the iv LCM formulation in pediatric subjects 
(≥1 month to <17 years of age). The EP0060 design is based on components of the study design 
for SP757, which evaluated iv LCM replacement in adults with partial-onset seizures, as well as 
based on design elements of other pediatric iv AED studies. In an effort to maximize the patient 
pool used in the evaluation of the safety of iv LCM in pediatric subjects, EP0060 has opened 
enrollment to include OLL and RxL subjects who are on a stable dose of oral LCM and elect to 
receive iv LCM as well as IIL subjects who are not currently taking LCM and initiate adjunctive 
LCM treatment using iv LCM. The expansion of the subject population occurred prior to the start 
of study enrollment. EP0060 also includes the option for RxL and IIL subjects to continue oral 
LCM treatment after completion of iv LCM, if determined clinically appropriate, in SP848. If 
required, a short-term supply of oral LCM solution will be provided for RxL and IIL subjects 
transitioning to start SP848 to ensure continuity of LCM treatment while allowing flexibility to 
schedule a clinical visit to initiate SP848. For RxL and IIL subjects who do not continue into 
SP848 (either by choice or not clinically appropriate), an additional telephone contact 
approximately 30 days after last dose of iv LCM IMP is added in order to collect final safety 
data. 
The iv LCM formulation at infusion durations of 15 to 60 minutes is approved at doses of 200 to 
400mg/day as adjunctive therapy in the treatment of partial-onset seizures in subjects ≥17 years 
of age with epilepsy when oral administration is temporarily not feasible, which can also include 
initiation of LCM treatment. Additionally in the EU, the iv formulation at infusion durations of 
15 to 60 minutes is also approved in pediatric subjects down to 4 years of age at maximum 
weight-based doses depending on weight band and whether LCM is administered as 
monotherapy or adjunctive therapy. An infusion duration of at least 30 minutes for 
administration >200mg per infusion (ie, >400mg/day) is preferred.
A weight-based LCM dosing scheme for pediatric subjects is being evaluated in Phase 3 
double-blinded, placebo-controlled studies and targets similar LCM plasma concentrations as 
those observed in adults given 400mg/day. As such, the target doses of LCM for the Phase 3 
studies are 8 to 12mg/kg/day; however, subjects entering EP0060 can be on a wider range of 
LCM doses based on the ranges of doses allowed in the long-term, open-label studies (2 to 
12mg/kg/day or 100 to 600mg/day). Thus, the iv LCM doses being evaluated in EP0060 will 
range from 2 to 12mg/kg/day or 100 to 600mg/day for OLL and RxL subjects, with a maximum 
dose of 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, this range of doses 
above also includes the pediatric starting dose of 2mg/kg/day (subjects <50kg) or 100mg/day 
(subjects ≥50kg), which is the same as those used in the Phase 3 pediatric LCM studies. The 
LCM dose at initiation of treatment should remain constant for at least 7 days prior to a LCM 
dose increase.
EP0060 will initially enroll at least 40 older pediatric subjects (Cohort 1) and will include at least 
20 subjects ≥12 to <17 years of age and at least 20 subjects ≥8 to <12 years of age. Cohort 2 will 
enroll approximately 44 subjects (with every attempt to enroll 20 subjects ≥4 to <8 years of age, 
12 subjects ≥2 to <4 years of age, and 12 subjects ≥1 month to <2 years of age) and will follow 
sequentially based on DMC recommendation. After completion of the first 20 subjects (Cohort 
1) and after completion of 20 subjects (Cohort 2) have received iv LCM over infusion durations 
of 30 to 60 minutes, the DMC will review the available safety and tolerability data. Based on 
their review, the DMC will recommend the target infusion duration for the remaining subjects in
the cohort (ie, 30 to 60 minutes for all remaining subjects or 15 to 30 minutes [only for subjects 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 30 of 240
who would directly benefit from an increased infusion rate, in the opinion of the investigator;
otherwise 30 to 60 minutes]), if the study/cohort should be stopped, and if the next cohort can be 
initiated (Section 12.7.2).
This design will result in a total exposure of approximately 100 pediatric subjects to assess the 
safety and tolerability of iv LCM in subjects ≥1 month to <17 years of age over a range of 
infusion durations. 
Taken together, the iv LCM dosing scheme and planned target infusion durations being 
evaluated in EP0060 (2 to 12mg/kg/day or 100 to 600mg/day; 15 to 60 minutes) allow for 
administration of a range of pediatric doses, and include infusion durations that are the same as 
those approved for adults and adolescents. 
6
SELECTION AND WITHDRAWAL OF SUBJECTS
6.1
Inclusion criteria
To be eligible to participate in EP0060, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject or by the parent(s) or legal 
representative. The Informed Consent form or a specific Assent form, where required, will be 
signed and dated by minors.
2. Subject is male or female from ≥1 month to <17 years of age.
3. Subject has a diagnosis of epilepsy with partial-onset seizures or primary generalized 
tonic-clonic seizures.
4. Subject meets 1 of the following criteria:
 OLL subject: Subject is currently receiving oral LCM as adjunctive or monotherapy as 
participants in an open-label long-term study (SP848, EP0034, or other pediatric study); 
OR,
 RxL subject: Subject is currently receiving prescribed oral LCM from commercial supply 
(eg, VIMPAT) as adjunctive or monotherapy; OR, 
 IIL subject: Subject is not currently receiving LCM and will receive iv LCM as 
adjunctive treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL 
subjects.
5. Subject is an OLL or RxL subject and meets both of the following criteria: 
 Subject has been administered LCM for the treatment of epilepsy for at least 2 weeks 
prior to Screening; AND, 
 Subject has been administered (OLL) or prescribed (RxL) oral LCM at a dose of 
2mg/kg/day to 12mg/kg/day (for subjects <50kg) or 100mg/day to 600mg/day (for 
subjects ≥50kg). Open-label study drug LCM (OLL) or prescribed oral LCM dose (RxL) 
must be stable for at least 3 days prior to first LCM infusion.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 31 of 240
Subject is an ILL subject and is on a stable dosage regimen of at least 1 AED. The daily 
dosage regimen of concomitant AED therapy must be kept constant for a period of at least 2 
weeks prior to Screening.
6. Subject is an acceptable candidate for venipuncture and iv infusion.
7. Subject is, in the opinion of the investigator, able to comply with all study requirements. 
Subject (or parent[s] or legal representative) is willing to comply with all study requirements.
8. Subject weighs ≥4kg.
6.2
Exclusion criteria
Subjects are not permitted to enroll in EP0060 if any of the following criteria are met:
1. Subject has previously received iv LCM in this study. 
2. Subject has any medical, neurological, or psychiatric condition that, in the opinion of the 
investigator, could jeopardize the subject’s health or compromise the subject’s ability to 
participate in EP0060.
3. Subject has clinically significant hypotension or bradycardia in the opinion of the 
investigator.
4. Subject ≥6 years of age has a lifetime history of suicide attempt (including an actual attempt, 
interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as 
indicated by positive responses (“Yes”) to either Question 4 or Question 5 of the C-SSRS at 
Screening.
5. Subject is taking monoamine oxidase A inhibitors (MAOI-A). 
For OLL subjects, enrollment in EP0060 is not permitted if any of the following additional 
criteria are met:
6. Subject has any ongoing AE in their long-term, open-label study that, in the opinion of the 
investigator, could jeopardize or would compromise the subject’s ability to participate 
EP0060 or the subject meets any of the criteria for required withdrawal from the long-term
open-label study.
For RxL and IIL subjects, enrollment in EP0060 is not permitted if any of the following 
additional criteria are met:
7. Subject has a medical condition that could reasonably be expected to interfere with drug 
absorption, distribution, metabolism, or excretion.
8. Subject has a known hypersensitivity to any component of the investigational medicinal 
product (IMP).
9. Subject is a female of childbearing potential and does not practice an acceptable method of 
contraception for the duration of participation in EP0060. 
a) Medically acceptable contraceptive method includes oral or depot contraceptive 
treatment with at least 30μg ethinylestradiol per intake (or 50μg if associated with 
carbamazepine [or other strong enzyme inducers, eg, phenobarbital, primidone, 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 32 of 240
oxcarbazepine]) which must be used in conjunction with a barrier method. Sexual 
abstinence is also an acceptable method of contraception. 
b) 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. Females of childbearing potential must have a negative pregnancy test at the 
Screening Visit.
10. Subject has creatinine clearance less than 30mL/min.
11. Subject has a clinically relevant ECG abnormality, in the opinion of the principal investigator 
(ie, second or third degree heart block at rest or a QT prolongation greater than 450ms).
12. Subject has hemodynamically significant heart disease (eg, heart failure).
13. Subject has an arrhythmic heart condition requiring medical therapy.
14. Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias.
15. Subject has an acute or subacutely progressive central nervous system disease. Subject has 
epilepsy secondary to a progressing cerebral disease or any other progressive or 
neurodegenerative disease (malignant brain tumor or Rasmussen syndrome).
16. Subject has a known cardiac sodium channelopathy, such as Brugada syndrome.
17. Lacosamide is intended for treatment of generalized convulsive status epilepticus. 
18. Subject has exclusively typical absence (Type IIA1) or atypical absence (Type IIA2) seizures 
(no other generalized seizure types are reported).
19. Subject has diagnosis of Dravet’s syndrome.
20. Subject has >2 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). 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 Case Report form (CRF).
If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at screening, 
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.
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation. This includes re-screening.
20a. Subject is currently participating in another study of an IMP.
For IIL subjects, enrollment in EP0060 is not permitted if the following additional criterion 
is met:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 33 of 240
21. Subject has been treated with LCM within the last 3 months prior to Screening.
6.3
Withdrawal criteria
Subjects are free to withdraw from EP0060 at any time, without prejudice to their continued 
care. The following criteria for subject withdrawal from EP0060 are outlined below. Additional 
discontinuation criteria for potential drug-induced liver injury are presented in Section 6.3.1.
Subjects must be withdrawn from EP0060 if any of the following events occur:
1. Subject experiences intolerable AEs and AEs associated with iv administration that, in the 
opinion of the investigator, preclude further participation in EP0060.
2. The subject requires more than 10 iv LCM doses.
3. The sponsor or a regulatory agency requests withdrawal of the subject.
4. Subject has corrected QT interval (QTc) ≥500ms that is confirmed by a cardiologist over 
read on any ECG.
5. Subject becomes pregnant during the study, as evidenced by a positive urine pregnancy test.
6. Subject develops a second- or third-degree atrioventricular (AV) block or another clinically 
relevant change in medical condition (or ECG) as determined by the investigator, or if the 
investigator feels it is in the interest of the subject to withdraw.
7. For subjects ≥6 years of age, subject has actual suicidal ideation since last visit as indicated 
by a positive response (“Yes”) to either Question 4 or Question 5 of the “Children’s Since 
Last Visit” version of C-SSRS. The subject should be referred immediately to a Mental 
Healthcare Professional and must be withdrawn from EP0060.
8. Subject is unwilling or unable to continue, or the parent/legal guardian is unwilling or unable 
to allow the subject to continue in EP0060.
9. Investigator decides that withdrawal from further participation would be in the subject’s best 
interest.
Participation in EP0060 may be withdrawn for any of the following reasons:
10. Subject experiences generalized convulsive status epilepticus.
11. Subject has any clinically relevant change in medical or psychiatric condition (if, in the 
opinion of the investigator, the change in condition warrants discontinuation from EP0060).
12. Subject requires a medication that is not permitted by the protocol (see Section 7.8.1).
13. Subject and/or delegated caregiver is noncompliant with EP0060 procedures or medication, 
in the opinion of the investigator.
14. Subject who initiated adjunctive LCM treatment in EP0060 and requires a change in LCM 
dose during the Treatment Period.
15. Subject electively administering LCM requires more than 2 iv doses. If, in the opinion of the 
investigator, there is a clinical need to administer more than 2 iv doses, the subject may 
remain in the study. The investigator should document the clinical need in the medical 
record/source documents. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 34 of 240
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject in advance. Investigators should also attempt to obtain information on subjects in the 
case of withdrawal. Withdrawal assessments, which are the same as those for Final Visit, will be 
recorded in EP0060. For subjects considered as lost to follow up, the investigator should make 
efforts (at least 1 phone call and 1 written message to the subject/subject’s parent or legal 
guardian), and document his/her efforts (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 Case Report form (CRF) must 
document the primary reason for withdrawal.
For subjects returning to a long-term, open-label study, withdrawal assessments from the 
long-term open-label study should be evaluated separately from the EP0060 withdrawal 
assessments. The Medical Monitor may provide guidance on whether the subject should return to 
continued treatment within the long-term open-label study (OLL subject), be allowed to enroll in 
SP848 (RxL and IIL subjects), or withdraw completely. For the particular withdrawal criterion of 
requiring more than 10 iv doses or if the route of LCM administration (iv) is the sole reason for 
withdrawal of consent, subjects may be allowed to return to their long-term open-label study 
(OLL subjects) or enroll in SP848 (RxL and IIL subjects) after discussion with and agreement 
from the Medical Monitor. If an OLL subject is advised to withdraw from the long-term 
open-label study (EP0034 or SP848), the subject will be required to return to the long-term 
open-label study to complete the required withdrawal and safety follow-up assessments.
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 immediately and permanently 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: 
x Subjects with either of the following:
 ALT or AST ≥5xULN
 ALT or AST ≥3xULN and coexisting total bilirubin ≥2xULN 
x Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and 
right upper quadrant pain or tenderness. Hypersensitivity symptoms include fever 
(without clear alternative cause), rash, or eosinophilia (ie, >5%).
The PDILI criterion below requires discussion with Medical Monitor to decide whether subject 
is allowed to continue on IMP. 
x 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 10.6.2. If subjects are unable to 
comply with the applicable monitoring schedule, IMP must be discontinued immediately.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 35 of 240
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 CRF must document the primary 
reason for IMP discontinuation.
7
STUDY TREATMENT(S)
7.1
Description of investigational medicinal product(s)
7.1.1
Lacosamide solution for infusion
Investigational medicinal product for infusion will be provided as LCM solution for infusion in 
glass iv vials (10mg/mL in a 20mL vial; each vial contains LCM 200mg). Both the iv vials and 
the carton containing the vials will be labeled for the study.
Further details regarding dilution and storage of LCM solution for infusion are provided in the 
IMP Handling Manual.
7.1.2
Lacosamide oral solution for RxL and IIL subjects transitioning to 
SP848
Lacosamide syrup/oral solution will be provided in a polyethylene terephthalate bottle 
(10mg/mL in 200mL bottle). The bottle will be labeled for the study. Study medication will be 
measured and administered via a dosing syringe.
Lacosamide oral solution will only be distributed to those RxL and IIL subjects who are eligible 
and choose to participate in SP848. This supply, if required, will be dispensed at Visit 2 in the 
event that additional time is needed to coordinate scheduling of Visit 1 of SP848, and any 
remaining oral LCM solution will be returned to the site at the Transition Visit.
7.2
Treatment(s) to be administered
7.2.1
Treatment Period 
During the Treatment Period, subjects will receive at least 1 dose of iv LCM at the dose levels 
noted below. The first iv LCM dose will be given on Day 1. If more than 1 infusion is given, iv 
LCM will be administered bid at approximately 12-hour intervals, once in the morning and once 
in the evening, for up to 10 doses (or up to 5 days) for clinical need administration or up to 2 
consecutive doses (over approximately 24 hours) for elective administration. 
Specific dosing regimens for subjects who will receive iv LCM replacement therapy for oral 
treatment (OLL and RxL subjects) or for subjects who will initiate adjunctive LCM treatment 
(IIL subjects) are as follows:
x Replacement for oral treatment: For OLL and RxL subjects, the iv LCM daily dose 
will be equivalent (mg-for-mg) to the subject’s current oral LCM dose or prescribed oral 
LCM (ie, VIMPAT) dose (always in bid regimen) of 2 to 12mg/kg/day or 100 to 
600mg/day. The first infusion must be equivalent to the subject’s stable oral LCM dose.
x Adjunctive LCM treatment initiation: For IIL subjects, the iv LCM daily dose will be 
2mg/kg/day for subjects <50kg or 100mg/day for subjects ≥50kg. As LCM is given bid, 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 36 of 240
the actual dose for the first infusion will be LCM 1mg/kg (subjects weighing <50kg) or
50mg (subjects weighing ≥50kg). For these subjects, the LCM dose should remain 
unchanged for the duration of the iv Treatment Period (see Section 6.3).
A calibrated infusion pump should be used for delivering the iv LCM dose at a constant rate over 
the target duration defined for the cohort. A previously unused vial must be administered for 
each dose. Dilution is not required prior to administration of iv LCM. If needed to obtain a total 
volume compatible with the specified infusion duration, the iv LCM solution can be diluted; iv 
LCM is compatible with the following diluents: dextrose 5%, lactated ringers, and normal saline 
(NaCl 0.9%). The total volume of diluent should be calculated not to exceed a total volume of 
fluid intake/day based on the Holliday-Segar equation as follows: 
x For children weighing ≤10kg: 100mL/kg body weight
x For children weighing >10 to ≤20kg: 1000mL + 50mL/kg for each kg body weight ≥10kg
x For children weighing ≥20kg: 1500mL + 20mL/kg for each kg body weight ≥20kg
Intravenous LCM administration should be completed within 4 hours after dilution.
For the first 20 subjects ≥8 to <17 years of age enrolled into Cohort 1 and the first 20 subjects 
≥1 month to <8 years in Cohort 2, iv LCM should be infused over a duration of 30 minutes but 
no longer than 60 minutes whenever possible. 
The duration of infusion for the remaining subjects in each cohort will be based on DMC 
recommendation: 
x EITHER target infusion duration of 15 minutes but no longer than 30 minutes only in 
subjects who would directly benefit from an increased infusion rate, in the opinion of the 
investigator. Subjects who will not directly benefit from a 15 to 30 minute infusion, in the 
opinion of the investigator, cannot receive the faster infusion. These subjects should receive 
an infusion of 30 minutes but no longer than 60 minutes.
x OR all remaining subjects will have a target infusion duration of 30 minutes but no longer 
than 60 minutes 
Further details on the timing of DMC recommendations regarding infusion duration are provided 
in Section 12.7.2.
For OLL and RxL subjects, the iv LCM dose can be modified after the first infusion when 
necessary for the safety of the subject or when the investigator deems it appropriate; however, 
modification should not occur until after the Day 1 PK samples have been taken. Modification of 
iv LCM dose is not permitted for IIL subjects.
A subject cannot receive iv LCM for more than 10 doses (up to 5 days) within the Treatment 
Period of EP0060 (or more than 2 consecutive doses [over approximately 24 hours] for elective 
administration. If a subject requires iv LCM treatment for more than 5 days, the subject may 
continue on iv VIMPAT, but he/she will need to discontinue EP0060. Upon 
completion/discontinuation of EP0060, OLL subjects are eligible to resume participation in their 
respective open-label study, according to the protocol requirements. If a subject is withdrawn 
from EP0060 due to requirement of more than 10 iv LCM doses, the subject may be allowed to 
return to their long term open-label study (OLL subjects) or enroll in SP848 (RxL and IIL
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 37 of 240
subjects) after discussion with and agreement from the Medical Monitor. If an OLL subject 
meets any other “must withdrawal” criteria for the respective open-label study, the subject will 
return to the open-label study to complete the appropriate withdrawal assessments and safety 
follow-up.
For RxL and IIL subjects, AED treatment will continue at the discretion of the treating 
physician, upon completion/discontinuation of EP0060. If determined clinically appropriate, 
these subjects will be given the option to continue oral LCM treatment for up to 2 years in 
SP848. If LCM treatment is not continued in SP848 (either by choice or not clinically 
appropriate), RxL and IIL subjects will be followed for approximately 30 days after the Final 
Visit in order to collect safety data. All concomitant medications taken during this 30-day period, 
including prescribed AEDs, will be collected at TC2.
If subjects need to discontinue LCM, OLL subjects should be tapered off LCM as specified in 
their long-term, open-label study or at the discretion of the treating physician for RxL subjects. 
For OLL subjects, this taper should occur as a part of the long-term, open-label study and not as 
a part of EP0060.
7.2.2
Transition oral lacosamide
Oral LCM solution will only be distributed to those RxL and IIL subjects who are eligible and 
choose to participate in SP848.
For OLL and RxL subjects, the oral LCM daily dose will be equivalent (mg-for-mg) to the 
subject’s current oral LCM dose or prescribed oral LCM (ie, VIMPAT) dose (always in bid 
regimen) of 2 to 12mg/kg/day.
For IIL subjects, the oral LCM solution daily dose (always in bid) will be 2mg/kg/day for 
subjects <50kg or 100mg/day for subjects ≥50kg if the subject has been taking LCM for less than 
7 days. If the subject has reached 7 days of LCM exposure, an increase in dose titration can be 
initiated.
7.3
Packaging
Lacosamide is manufactured, packaged, and labeled according to Good Manufacturing Practice 
guidelines and applicable laws or regulations. Lacosamide will be suitably packaged in such a 
way as to protect LCM from deterioration during transport and storage. 
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Council for 
Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and Good Manufacturing 
Practice 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 LCM at the site. 
Lacosamide stored by the investigator is to be kept in a secured area with limited access 
according to the storage conditions mentioned on the label.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 38 of 240
Appropriate storage conditions must be ensured by controlling the temperature and by 
completion of a temperature log in accordance with local requirements on a regular basis, 
showing minimum and maximum temperatures reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual.
In the case of dispensing oral LCM solution, the investigator (or designee) will instruct the 
subject’s parent or guardian to store the IMP following the instructions on the label.
7.6
Drug accountability
A Drug Accountability form will be used to record LCM dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any LCM lost, damaged (due to breakage or wastage), not used, partially 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 LCM until returned or destroyed by a UCB representative.
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 LCM 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, unused, damaged, and/or expired LCM must be reconciled and either 
destroyed at the site according to local laws, regulations, and UCB SOPs or returned to UCB (or 
designee). 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 drug accountability
Drug accountability must be recorded on the Drug Accountability form by site staff and 
reviewed by the UCB representative during periodic monitoring visits. 
7.8
Concomitant medication(s)/treatment(s)
7.8.1
Permitted and prohibited concomitant treatments (medications and 
therapies)
Stable use of amphetamines and sedative antihistamines is permitted during the study. 
Use of the following concomitant treatments (medications and therapies) is prohibited during 
EP0060:
x MAOI-A inhibitors
x Cannabidiols not approved or indicated for epilepsy by local health authority
Therapy which becomes necessary in the investigator’s opinion during the course of the study 
must not be refused to a subject even if described above as therapy that is expressly not 
permitted. In such cases, the subject’s participation in EP0060 may be discontinued.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 39 of 240
7.9
Blinding
This is an open-label study. 
7.10
Randomization and numbering of subjects
Subjects will not be randomized in EP0060. For an OLL subject, the unique identification 
number assigned to them in that study will be used to identify them and maintain subject 
confidentiality throughout EP0060. A unique identification number in EP0060 will be assigned 
for RxL and IIL subjects.
8
STUDY PROCEDURES BY VISIT 
Detailed tabular schedules of study procedures are provided in Section 5.2.
8.1
Screening/Baseline Period
8.1.1
Visit 1a and Visit 1b (Day -7 to Day 1) Screening and/or Baseline
Prior to the conduct of any study-related procedures, a complete explanation (both verbally and 
written) of the nature and purpose of the study will be given to the subject (when possible or as 
required according to local IRBs/IECs) and the subject’s parent/legal guardian by the 
investigator (or designee). The subject’s parent/legal guardian will be requested to sign and date 
the IRB/IEC-approved Informed Consent form. When possible, or as required by the local
IRB/IEC, an IRB/IEC-approved written Assent form will also be properly executed and 
documented. During the Screening Period, subjects will be evaluated for their suitability for 
enrollment. The Screening Period assessments may be conducted on more than 1 day and begin 
up to 7 days prior to Day 1 (Visit 2). 
The Screening and/or Baseline Visit can occur on the same day as the first iv LCM infusion 
(Day 1), if necessary, provided all test results (ie, 12-lead ECG and laboratory results) are 
available and reviewed to assess inclusion and exclusion criteria prior to enrollment/treatment in 
the study. For all subjects, laboratory results obtained for routine diagnostic and medical care can 
be used whenever possible if collected no more than 24 hours prior to Screening/Baseline Visit 
in order to minimize blood loss associated with the study. At the Screening/Baseline Visit, the 
use of a central or local laboratory is at the discretion of the investigator.
If Screening/Baseline do not occur on the same day as the first infusion, oral LCM will be 
administered for OLL and RxL subjects during the Screening/Baseline Period from their 
open-label study or prescribed LCM supply in accordance with each subject’s current stable 
LCM dosage regimen of 2 to 12mg/kg/day or 100 to 600mg/day. For IIL subjects, no LCM will 
be administered during the Screening Period.
Each subject’s eligibility for the study will be determined on the basis of the inclusion/exclusion 
criteria at Visit 1a and/or Visit 1b. Demographic data will be collected at Visit 1a. The following 
pretreatment assessments will be carried out at Visit 1a:
x Height and weight 
x Medical procedures
x Procedure history
x Diagnosis of epilepsy
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 40 of 240
x Childbearing potential
x Complete medical history for RxL and IIL subjects (a medical history update will be 
captured in the previous long-term open-label study for OLL subjects) 
x For OLL and RxL subjects, LCM dosing history (including formulation, date, and time of 
use, and dose and unit during the last 3 days)
x Prior and concomitant medication(s) assessment (prior medications will only be collected 
for direct-enroll subjects)
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose),  
VNS settings, and/or use of ketogenic diet
x Urine pregnancy testing for subjects of childbearing potential 
x Withdrawal criteria
x Complete neurological examination
x Complete physical examination
x Blood sample for clinical chemistry and hematology 
x Vital signs (BP and pulse rate) assessment (measured on subjects who have rested [sitting 
or supine] for at least 3 minutes, when feasible)
x 12-lead ECG (conducted on subjects who have rested [sitting or supine] at least 3 minutes 
prior to each ECG recording, when feasible)
x AE reporting (AEs occurring since signature of Informed Consent form). Ongoing AEs 
from the long-term open-label studies will be followed, as well as recording of new AEs 
during EP0060.
x C-SSRS (for subjects ≥6 years of age). For subjects <6 years, signs and symptoms of
depression will be evaluated as described in Section 10.7.5.
x Seizure history for RxL and IIL subjects
If Screening/Baseline and the first infusion do not occur on the same day, oral LCM 
administration for OLL and RxL subjects will continue in accordance with each subject’s LCM 
dosage regimen and using the subject’s open-label study or prescribed oral LCM supply, 
respectively.
The following assessments will be carried out at Visit 1b if Screening and Baseline occur on 
separate days:
x Verification that the subject continues to meet the inclusion criteria
x For OLL and RxL subjects, the LCM dosing history will be collected (including 
formulation, date, and time of use, and dose and unit during the last 3 days)
x Prior and concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose), 
VNS settings, and/or ketogenic diet
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 41 of 240
x AE reporting (AEs occurring since signature of Informed Consent form)
x Blood sample for clinical chemistry and hematology (Repetition of laboratory 
assessments is at the discretion of the investigator if Visit 1b is on a separate day from 
Visit 1a.)
x Withdrawal criteria
x Vital signs (BP and pulse rate) assessment (measured on subjects who have rested [sitting 
or supine] for at least 3 minutes, when feasible)
x 12-lead ECG (conducted on subjects who have rested [sitting or supine] at least 3 minutes 
prior to each ECG recording, when feasible)
x C-SSRS (for subjects ≥6 years of age). For subjects <6 years, signs and symptoms of 
depression will be evaluated as described in Section 10.7.5.
x Medical procedures
x Medical history update for OLL subjects, or complete medical history for RxL and IIL 
subjects 
x Urine pregnancy testing for subjects of childbearing potential
x Brief physical examination
x Brief neurological examination
If Screening/Baseline and the first infusion do not occur on the same day, oral LCM 
administration for OLL and RxL subjects will continue in accordance with each subject’s LCM 
dosage regimen and using the subject’s open-label study or prescribed oral LCM supply, 
respectively.
8.2
Treatment Period
8.2.1
Visit 2 (Day 1)
Intravenous LCM infusion treatment will begin at this visit. Subjects will receive at least 1 dose 
of iv LCM. If more than 1 infusion is given, iv LCM will be administered bid at approximately 
12-hour intervals, once in the morning and once in the evening, for up to 10 doses (or up to 5 
days) for clinical need administration or up to 2 consecutive doses (over approximately 24 hours) 
for elective administration. 
Screening laboratory assessments may be conducted up to and including the day of the infusion 
provided they are reviewed and meet inclusion/exclusion criteria prior to the infusion. 
Section 8.1.1 details under what conditions laboratory results within 24 hours of signing the 
Informed Consent form can be used. 
The following assessments will be carried out:
x Intravenous LCM infusion
x Medical procedures
x Prior and concomitant medication(s) assessment
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 42 of 240
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose), 
VNS settings, and/or use of ketogenic diet
x Withdrawal criteria
x AE reporting
x 12-lead ECG (approximately 20 minutes prior to iv LCM infusion and at approximately 
15, 30, 60 minutes, and 2 hours from the start of iv LCM infusion) (conducted on 
subjects who have rested [sitting or supine] for at least 3 minutes prior to each ECG 
recording, when feasible)
x Vital signs of BP and pulse rate (approximately 10 minutes prior to iv LCM infusion and 
at approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of iv LCM 
infusion) (measured on subjects who have rested [sitting or supine] for at least 3 minutes, 
when feasible)
x Blood sample for LCM PK (Blood draws will be performed from a region of the body 
that is different from the region where the iv LCM infusion will be administered at the 
time points described in Section 9. An indwelling peripheral cannula used for the iv LCM 
infusion may not be used for PK blood sampling.) 
x C-SSRS (for subjects ≥6 years of age) after infusion. For subjects <6 years, signs and 
symptoms of depression will be evaluated as described in Section 10.7.5.
x Brief physical examination
x Brief neurological examination
x For RxL and IIL subjects who are eligible and choose to participate in the long-term 
open-label oral LCM study SP848 after completion of EP0060, a short-term oral LCM 
solution will be dispensed at Visit 2. This supply is to allow continuity of LCM treatment 
after the last iv LCM infusion and the scheduled Transition Visit. Oral LCM solution 
administration should begin approximately 12 hours after the final iv LCM infusion.
If a second iv LCM infusion is given, it will be administered at approximately 12 hours after the 
start of the first infusion, and the following assessments will be carried out:
x Intravenous LCM infusion
x AE reporting
x 12-lead ECG (approximately 20 minutes prior to iv LCM infusion and at approximately 
15, 30, 60 minutes, and 2 hours from the start of iv LCM infusion) (conducted on 
subjects who have rested [sitting or supine] for at least 3 minutes prior to each ECG 
recording, when feasible)
x Vital signs of BP and pulse rate (approximately 10 minutes prior to iv LCM infusion and 
at approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of iv LCM 
infusion) (measured on subjects who have rested [sitting or supine] for at least 3 minutes, 
when feasible)
x Withdrawal criteria
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 43 of 240
x Concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose), 
VNS settings, and/or use of ketogenic diet
If the subject has more than 1 iv LCM infusion, it is optional to also collect blood samples for 
LCM PK before and after the final iv LCM infusion at the time points described in Section 9. In 
addition, during the course of the study, additional blood samples for PK analysis can be taken at 
the discretion of the investigator, especially in the event of a relevant treatment-emergent AE.
8.2.2
Visit 3 (Day 2 to Day 5)
If iv LCM treatment is continued after Day 1, assessments for Visit 3 must be completed each 
day of iv LCM treatment in EP0060. Assessments for Visit 3 (Day 2 to 5) are the same as those 
described for Visit 2 (Day 1) in Section 8.2. If the subject has more than 1 iv LCM infusion, it is 
optional to also collect blood samples for LCM PK before and after the final iv LCM infusion at 
the time points described in Section 9. In addition, during the course of the study, additional 
blood samples for PK analysis can be taken at the discretion of the investigator, especially in the 
event of a relevant treatment-emergent AE. 
8.3
Unscheduled Visit
The following assessments will be carried out during the Unscheduled Visit:
x Medical procedures
x Concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose), 
VNS settings, and/or use of ketogenic diet
x AE reporting
x BP and pulse rate (measured on subjects who have rested [sitting or supine] for at least 
3 minutes, when feasible)
x Withdrawal criteria
x C-SSRS (for subjects ≥6 years of age). The C-SSRS assessment should be completed if 
the Unscheduled Visit is due to an AE. For subjects <6 years, signs and symptoms of 
depression will be evaluated as described in Section 10.7.5.
x Brief physical examination
x Brief neurological examination
Additional assessments can be performed at the investigator’s discretion, including collection of 
a blood sample for LCM PK if the reason for the Unscheduled Visit is an AE.
8.4
End-of-Study Period
8.4.1
Final Visit (Day 1 to 6)/Termination Visit
The Final Visit may occur on the same day as the last infusion, time permitting. Otherwise, the 
Final Visit should occur on the following day.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 44 of 240
The following assessments will be carried out after the last dose of iv LCM for subjects who 
complete the study, discontinue the study, or withdraw from the study prematurely:
x Medical procedures
x Concomitant medication(s) assessment
x Urine pregnancy testing for subjects of childbearing potential 
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose), 
VNS settings, and/or use of ketogenic diet
x AE reporting
x Complete physical examination
x Complete neurological examination
x Blood sample for clinical chemistry and hematology which must be analyzed at the 
central laboratory
x 12-lead ECG (conducted on subjects who have rested [sitting or supine] for at least 3 
minutes prior to each ECG recording, when feasible)
x BP and pulse rate (measured on subjects who have rested [sitting or supine] for at least 
3 minutes, when feasible)
x Withdrawal criteria
x Oral LCM administration, if applicable:
 For OLL subjects, oral LCM administration will continue in accordance with each 
subject’s LCM dosage regimen using the subject’s open-label study LCM supply
 For RxL subjects who are not eligible or do not wish to continue LCM treatment in 
SP848, oral LCM administration may continue from the subject’s prescribed LCM 
supply at the physician’s recommended dosage regimen.
 For RxL and IIL subjects who are eligible and wish to enroll in SP848, oral LCM 
administration, from the short-term oral LCM solution that was dispensed at Visit 2,
should begin approximately 12 hours after the final iv LCM infusion regardless of 
when the Final Visit occurs. Additional assessments will be conducted at the 
Transition Visit, as outlined in Section 8.4.3.
x C-SSRS (for subjects ≥6 years of age) For subjects <6 years, signs and symptoms of 
depression will be evaluated as described in Section 10.7.5.
8.4.2
Telephone Contact 1 (Day 2 to Day 9)
One to 3 days after the Final Visit, a safety follow-up/telephone assessment will be conducted 
during the End-of-Study Period. The following assessments will be collected:
x Medical procedures
x Concomitant medication(s) assessment
x AE reporting
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 45 of 240
x Information regarding LCM dosing since Final Visit
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
During the contact, the site should inquire as to whether the subject noted any change at the 
site of the infusion.
8.4.3
Transition Visit (Day 1 to Day 13)
For RxL and IIL subjects who are eligible and wish to enroll in SP848, the Final Visit and 
Transition Visit may occur on the same day or may occur up to 7 days after the Final Visit. The 
Transition Visit for EP0060 should occur on the same day as Visit 1 in SP848.
The following assessments will be conducted at the Transition Visit if the visit is not conducted 
on the same day as the Final Visit:
x Collection of the short-term oral LCM solution, if dispensed at Visit 2 
x Information regarding LCM dosing since Final Visit
x Concomitant medication(s) assessment
x AE reporting
Additional assessments for enrollment in SP848 (Visit 1) are detailed within the SP848 protocol.
8.4.4
Telephone Contact 2 (Day 29 to Day 37)
Thirty days (±2 days) after the Final Visit, a safety follow-up/telephone assessment will be 
conducted during the End-of-Study Period (29 to 37 days after Visit 2/Day 1). This assessment 
will only occur for those subjects who directly enrolled in EP0060 and will not be continuing 
LCM therapy in SP848. 
The following assessments will be collected:
x Concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or use of ketogenic diet
x AE reporting
x Information regarding LCM dosing since Telephone Contact 1
x Medical procedures
During the contact, the site should inquire as to whether the subject noted any change at the 
site of the infusion.
9
ASSESSMENT OF PHARMACOKINETICS
Blood samples for the determination of LCM and SPM 12809 concentrations will be collected 
according to the tabular schedules of study procedures (see Section 5.2). In each case, the time 
the subject received the most recent dose of IMP and the time of blood sampling must be 
recorded.
During the Treatment Period, plasma samples will be taken for LCM and SPM 12809
determination after ECG and vital signs have been taken. Plasma samples will be obtained from 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 46 of 240
a different region of the body from the region in which the solution for infusion was 
administered, at the following time points:
First iv LCM infusion (Day 1) – required samples:
x Predose (within 1 hour prior to iv LCM dose) for OLL and RxL subjects
x Postdose (within 1 to 4 hours after end of iv LCM infusion)
Final iv LCM infusion (Day 2 to 5/Early Termination) – optional samples:
x Predose (within 1 hour prior to iv LCM dose)
x Postdose (within 1 to 4 hours after end of iv LCM infusion)
Additional blood samples for PK analysis can be taken at the discretion of the investigator, 
especially in the event of a relevant treatment-emergent AE.
The study-related blood loss (including any losses in the maneuver), per study subject, will not 
exceed 3% of the total blood volume during a period of 4 weeks and will not exceed 1% at any 
single time. The total volume of blood is estimated at 80 to 90mL/kg body weight; 3% is 2.4mL 
of blood per kg of body weight. With today’s microanalytical techniques, plasma samples for 
drug level determinations can be small, with less than 1mL needed.
Details of plasma sample collection and processing, sample labeling, and shipment will be 
provided in the laboratory manual.
10
ASSESSMENT OF SAFETY
10.1
Adverse events
10.1.1
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 an IMP, 
whether or not related to the IMP.
In order to ensure complete safety data collection, all AEs occurring during EP0060 (ie, after the 
signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol (excluding hospitalization procedures for other conditions other than 
those related to epilepsy), must be reported in the CRF 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 Screening/Baseline assessments.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 47 of 240
10.1.2
Procedures for reporting and recording adverse events
The subject (or parent[s] or legal representative) will be given the opportunity to report AEs to 
the investigator spontaneously. A general prompt will also be given by the investigator at each 
study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
10.1.3
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 CRF and 
source documents should be consistent. Any discrepancies between the subject’s own words (or 
the words of parent[s] or legal representative) 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 CRF (including judgment of relationship to IMP)
are described in the CRF Completion Guidelines.
10.1.4
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 EP0060 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 
investigator must provide a justification. The follow up will usually be continued for 30 days 
after the subject has discontinued IMP. Any ongoing AEs at the end of EP0060 for the subjects 
enrolled in the open-label studies will not need to be re-recorded in the long-term, open-label 
study.
10.1.5
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:
x 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”
x 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
10.1.6
Pregnancy
If an investigator is notified that a subject has become pregnant after the first dose of iv LCM 
infusion, 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:
x The subject may need to discontinue iv LCM. The decision to stop the intake of iv LCM 
will be at the discretion of the investigator. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 48 of 240
x A Safety Follow-Up Visit should be scheduled 1 to 3 days after the subject has 
discontinued her iv LCM infusion.
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 
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.
A pregnancy becomes a serious adverse event (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.
10.1.7
Suspected transmission of an infectious agent via a medicinal 
product
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE; such cases must be reported immediately, recorded in 
the AE module of the CRF, and followed as any other SAE. Any organism, virus, or infectious 
particle (eg, prion protein transmitting transmissible spongiform encephalopathy), pathogenic or 
nonpathogenic, is considered an infectious agent.
10.1.8
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the CRF. 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).
10.1.9
Safety signal detection
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the IMP so that investigators, clinical study subjects, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible.
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the PS representative.
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 49 of 240
signs, laboratory, or ECG results) for which data will be periodically reviewed during the course 
of the study.
10.2
Serious adverse events
10.2.1
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 at least 1 of the following criteria:
x Death
x Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred 
in a more severe form.)
x Significant or persistent disability/incapacity
x Congenital anomaly/birth defect (including that occurring in a fetus)
x 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, but are not limited to, potential Hy’s Law [see 
Section 10.3], 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.)
x 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 or 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.)
10.2.2
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) 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 50 of 240
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 that the investigator, when completing the SAE report form, includes 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.
10.2.3
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. This 
follow-up requirement applies to AEs, SAEs, and AEs of special interest; further details 
regarding follow up of PDILI events are provided in Section 10.6.2.
Information on SAEs obtained after clinical database lock will be captured through the Patient 
Safety database without limitation of time.
10.3
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.
The following are AEs of special interest:
x The following arrhythmias: atrial fibrillation/flutter, ventricular tachycardia or 
fibrillation, AV block (second-degree Type I and II and third-degree), and marked 
bradycardia (<45beats/min)
x Syncope or loss of consciousness (other than seizure related)
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 51 of 240
x Serious suspected multiorgan hypersensitivity reactions
Serious suspected multiorgan hypersensitivity cases may be identified and reported to the 
sponsor by the investigator using the following algorithm as agreed with the US Food and Drug 
Administration; an AE or laboratory value (as defined in the following text) 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 1 of the following: fever, rash, lymphadenopathy, or eosinophilia.
Treatment-emergent abnormal laboratory value criteria suggestive of internal organ involvement 
or eosinophilia:
 Eosinophils % ≥10%
 Eosinophils absolute ≥0.5G/L
 Neutrophils absolute <1.5G/L
 Platelets ≤100G/L
 ALT ≥2×ULN
 AST ≥2×ULN
x 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.
10.4
Immediate reporting of adverse events
The following AEs must be reported immediately by the investigator to UCB:
x SAE: AE that the investigator classifies as serious by the above definitions regardless of 
causality
x Suspected transmission of an infectious agent via a medicinal product
x AE of special interest (see Section 10.3)
10.5
Anticipated serious adverse events
The following list of anticipated SAEs is anticipated to occur in the epilepsy population at some 
frequency that is independent of drug exposure. 
This list does not change the investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 10.2.2.
Table 10‒1: Anticipated SAEs for the pediatric epilepsy population
MedDRA SOC
MedDRA PT
Congenital, familial and genetic disorders
Teratogenicity
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 52 of 240
Table 10‒1: Anticipated SAEs for the pediatric epilepsy population
MedDRA SOC
MedDRA PT
General disorders and administrative site 
conditions
Sudden unexplained death in epilepsy
Nervous system disorders
Convulsiona
Incontinence
Status epilepticus
Pregnancy, puerperium and perinatal disorders
Abortion spontaneous
Psychiatric disorders
Psychotic behavior
Abnormal behavior
Anxiety
Sleep disorder
Reproductive system and breast disorders
Menstrual disorder
MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; SAE=serious adverse event; 
SOC=system organ class
a Convulsion if consistent with the seizure type known for the subject. 
10.6
Laboratory measurements
Blood specimens for routine assay of hematology and clinical chemistry testing will be collected 
according to the tabular schedule of study assessments (Section 5.2). To minimize risk from 
blood loss associated with this study, local laboratory results obtained for routine diagnostic and 
medical care can be used whenever possible if collected no more than 24 hours prior to 
Screening/Baseline Visit. Use of the central or local laboratory is at the discretion of the 
investigator for all visits except the Final Visit. The central laboratory must be used for 
laboratory samples collected at the Final Visit. Samples will be prepared and evaluated by a 
central laboratory as described in the laboratory manual.
All laboratory values that are outside the normal reference range must be assessed by the 
investigator for clinical relevance. The following parameters will be measured:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 53 of 240
Table 10‒2: Laboratory tests
Hematology
Clinical chemistry
Hematocrit
Hemoglobin
Platelet count
Red blood cell count
White blood cell (WBC) count
WBC differential count
Calcium
Phosphorus
Serum electrolytes (sodium, potassium, chloride, bicarbonatea)
Creatinine
Blood urea nitrogen
AST
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Alkaline phosphatase
Gamma-glutamyltransferase
Glucose
Albumin
Total protein
Cholesterol
Triglycerides
Uric acid
ALT=alanine aminotransferase; AST=aspartate aminotransferase; WBC=white blood cell
a Bicarbonate testing is optional for subjects weighing less than 8kg. Consider testing for bicarbonate in subjects 
weighing less than 8kg in cases of suspected metabolic disturbances such as metabolic acidosis. 
10.6.1
Pregnancy testing
Females of childbearing potential will have pregnancy testing performed according to the tabular 
schedule of study procedures (Section 5.2).
10.6.2
Liver function tests and evaluation of PDILI
The PDILI IMP discontinuation criteria for this study are provided in Section 10.6.2.2 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 10.3), and, if applicable, also reported as an 
SAE (see Section 10.2.1). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 10‒3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 10.6.2.1). 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 10.6.2.4).
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 54 of 240
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 CRF 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. 
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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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 55 of 240
Table 10‒3: Required investigations and follow up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptoms
a of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULN
b
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 10.6.2.3);
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
≥5xULN
NA
NA
≥3xULN
NA
Yes
≥3xULN 
(and ≥2x 
Baseline) 
and
<5xULN
<2xULN
No
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Medical Monitor 
required if the 
criterion that allows 
for IMP continuation 
is met.
Further investigation 
– immediate IMP 
discontinuation not 
required (see 
Section 10.6.2.2).
Not required 
unless otherwise 
medically 
indicated (at 
discretion of 
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 10.6.2.3).
Monitoring of liver chemistry 
values at least twice per week 
until values normalize, stabilize, 
or return to within Baseline 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 56 of 240
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 10.6.2.1. 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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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 57 of 240
10.6.2.1
Consultation with 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 Section 10.6.2.3) and SAE report (if applicable).
10.6.2.2
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 10‒3 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.
10.6.2.3
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 10‒4 (laboratory measurements) and Table 10‒5 (additional information). Results of the 
laboratory measurements and information collected are to be submitted to the sponsor on the 
corresponding CRF. 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:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 58 of 240
Table 10‒4: 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
Hematocrit
Hemoglobin
Platelet count
RBC count
WBC count
WBC differential 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
ALT
AST
ALP
GGT
Albumin
Additional
Prothrombin time/INR
a
Serum pregnancy test
PK sample
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 59 of 240
Table 10‒4: PDILI laboratory measurements
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine 
phosphokinase; GGT=gamma-glutamyltransferase; 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; RBC=red 
blood cell; RNA=ribonucleic acid; ULN=upper limit of normal; WBC=white blood cell
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 10‒5: 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:
x 
History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty 
liver disease”)
x 
Adverse reactions to drugs
x 
Allergies
x 
Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 antitrypsin 
deficiency)
x 
Recent travel 
x 
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
10.6.2.4
Follow-up evaluation
Potential drug-induced liver injury events require follow-up monitoring as described in 
Table 10‒3. 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.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 60 of 240
10.7
Other safety measurements
10.7.1
Vital signs, body weight, and height
Noninvasive measurements of BP (systolic and diastolic) and pulse rate will be performed after 
at least 3 minutes at rest, when feasible, according to the tabular schedule of study assessments 
(Section 5.2). Body weight will be determined without shoes and wearing light clothing, and 
height will be measured without shoes; body weight and height will be assessed according to the 
tabular schedule of study procedures (Section 5.2).
10.7.2
12-lead ECG
Standard 12-lead ECGs will be performed according to the tabular schedule of study procedures 
(Section 5.2).
Care should be taken to assure proper lead placement and quality ECG recordings. Subjects 
should rest at least 3 minutes prior to each recording and should be motionless during the 
recording, when feasible.
10.7.3
Overall ECG interpretation
An immediate initial review of the ECGs will be conducted locally by the investigator, 
subinvestigator, or qualified designated reader. If this reading identifies abnormal ECG findings 
that are assessed by the investigator or subinvestigator to be clinically significant, then the ECG 
should be repeated in 1 hour, unless circumstances require a more rapid assessment. If the 
clinically significant abnormality is confirmed by the repeat ECG or if the investigator feels it is 
medically necessary, the subject must be withdrawn from EP0060 (see Section 6.3). The 
investigator may consult with the cardiologist at the central ECG laboratory to confirm the 
presence of a clinically significant ECG abnormality. It remains the responsibility of the 
investigator to decide whether an ECG finding is of clinical significance on the basis of the 
complete clinical picture and whether this finding influences the subject’s participation in 
EP0060. Additionally, the ECGs will be sent to a central reader for review.
10.7.4
Physical examination
10.7.4.1
Complete physical examination
The complete physical examination will include cardiac and respiratory function via 
auscultation, and review of all body systems. Clinically significant physical examination findings 
are to be reported as AEs.
10.7.4.2
Brief physical examination
The brief physical examination will include a review of the following body systems: 
cardiovascular, pulmonary, abdominal (hepato-gastrointestinal), and dermatologic.
10.7.5
Assessment of suicidality
Suicidality will be assessed by trained study personnel using the C-SSRS (Columbia University 
Medical Center, 2008). For subjects ≥6 years of age, this scale will be used for screening as well 
as to assess suicidal ideation and behavior that may occur during the study. The C-SSRS will be 
completed according to the tabular schedule of study procedures (Table 5‒1). If the Screening 
and Baseline visit is on the same day, the C-SSRS does not need to be completed twice. The 
C-SSRS should be performed once per day during the Treatment Period. If Screening/Baseline 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 61 of 240
and Visit 2 occur on the same day, 2 assessments should be completed with 1 predose and 1 after 
infusion.
All subjects who are ≥6 years of age will complete the “Baseline/Screening” version of the 
C-SSRS at Visit 1 and will complete the “Since Last Visit” version at subsequent visits. If a 
subject becomes 6 years of age during the study, the "Already Enrolled" version of the C-SSRS 
should be used at the first visit at which the subject is 6 years of age and the “Since Last Visit” 
version used at subsequent visits.
The C-SSRS is not validated for subjects <6 years of age and will not be used for this population. 
Subjects should be monitored for any changes in mood, ideas, or behavior for warning signs of 
depression. The investigator should be aware of common warning signs that might be a signal for 
risk of depression. For common signs and symptoms of depression in children younger than 
6 years old, reference should be made to the current version of the Diagnostic and Statistical 
Manual of Mental Disorders. Parents and caregivers should also be advised accordingly and 
effort should be made at clinic visits to specifically assess potential depression.
10.7.6
Neurological examination
10.7.6.1
Complete neurological examination
The complete neurological examination will include selected assessment of general neurological 
status (level of consciousness, mental status, speech), cranial nerves, reflexes, motor system 
(general motor status, muscle strength, muscle tone), coordination/cerebellar function, and 
sensation. Clinically significant neurological examination findings are to be reported as AEs.
10.7.6.2
Brief neurological examination
The brief neurological examination will include selected assessment of mental status, cranial 
nerves, and coordination/cerebellar function.
11
STUDY MANAGEMENT AND ADMINISTRATION 
11.1
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 IEC/IRB or sponsor.
After implementation of such measure, the investigator must notify the CPM of the sponsor 
within 24 hours and follow any local regulatory requirements.
11.2
Monitoring
UCB (or designee) will monitor the study according to UCB (or designee) approved Standard 
Operating Procedures (SOPs), ICH-GCP guidelines, and applicable regulatory requirements, to 
ensure that study initiation, conduct, and closure are adequate.
The investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s).
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 62 of 240
The investigator will allow UCB (or designee) to periodically review all CRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress 
of the study, verify the accuracy and completeness of CRFs, ensure that all protocol 
requirements, applicable authorities regulations, and investigator’s obligations are being fulfilled, 
and resolve any inconsistencies in the study records.
11.2.1
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). Printouts of electronic CRF screens are not considered 
acceptable source documents.
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.
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.
11.2.2
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 CRF should be supported by source 
documents, unless otherwise specified in Section 11.2.1.
11.3
Data handling
11.3.1
Case Report form completion
The study is performed using electronic data capture (EDC); the investigator is responsible for 
prompt reporting of accurate, complete, and legible data in the electronic CRFs and in all 
required reports.
Any change or correction to the CRF 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 need to be reapproved by the investigator.
The investigator should maintain a list of personnel authorized to enter data into the electronic 
CRF.
Detailed instructions will be provided in the CRF Completion Guidelines.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 63 of 240
11.3.2
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. As the study is performed using EDC, the data are entered into the electronic CRFs 
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.
11.3.3
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.
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.
11.4
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, 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 IRB/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.
11.5
Archiving and data retention
The investigator will maintain adequate records for the study, including CRFs, 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 
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
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relocate or move the study-related files to a location other than that specified in the sponsor’s 
trial master file.
11.6
Audit and inspection
The investigator will permit study-related audits mandated by UCB, 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 IRB/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).
11.7
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.
12
STATISTICS
Selected disposition, exposure, demographic, and Baseline summaries will be presented by 
cohort and infusion duration, cohorts overall, and all subjects overall. Within cohort and infusion 
duration, presentation will include the IIL subject group and the OLL and RxL subject group.
Descriptive statistics will be displayed to provide an overview of the Baseline characteristics, 
PK, and safety results.
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan.
12.1
Definition of analysis sets
The Safety Set (SS) will include subjects who received at least 1 dose of EP0060 study drug 
LCM (oral and/or iv). Selected safety summaries will be presented for the SS.
The Safety Set iv (SS-iv) will include subjects in the SS who received at least 1 dose of EP0060 
study drug iv LCM. The SS-iv will be the primary analysis set for the analysis of safety data.
The Pharmacokinetic-Per Protocol Set (PK-PPS) will include all subjects in the SS-iv having 
provided at least 1 measurable postdose plasma sample (with recorded sampling time) on at least 
1 study day with documented iv LCM intake times and without important protocol deviations 
impacting the interpretability of the PK analysis.
12.2
General statistical considerations
All computations for the non-PK analyses will be performed using SAS® version 9.1 or later 
(SAS Institute, NC, USA).
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 65 of 240
Summary statistics will consist of frequency tables for categorical variables. For continuous 
variables, descriptive statistics (number of available observations, mean, median, standard 
deviation [SD], minimum, and maximum) will be tabulated. For PK parameters, the coefficient 
of variation (CV) and geometric mean may also be presented.
12.3
Planned pharmacokinetic analyses
Descriptive statistics for LCM and SPM 12809 plasma concentrations, including but not limited 
to geometric mean and CV, will be computed for pre-infusion and post-infusion time points on 
each infusion day where LCM and SPM 12809 plasma are collected. 
12.4
Planned safety analyses
Safety analyses will be presented by age cohort. 
Inferential statistical tests are not planned for the safety variables. In general, for continuous 
safety variables (eg, ECG measurements including QTc, and vital signs measurements), the 
descriptive analyses (n, mean, SD, median, minimum, maximum) for the actual measurement 
and its change from Baseline (defined as pre-iv LCM measurement) will be presented by 
day/time of collection for each infusion day. When analyzing categorical data, the number and 
percentage of subjects in each category will be presented. In addition, shift tables may be used to 
evaluate the number and percentage of subjects having a different post-iv LCM status when 
compared with their pre-iv LCM status.
12.5
Handling of protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on the primary outcomes for an individual subject. The criteria for identifying 
important protocol deviations will be defined within the appropriate protocol-specific document. 
Important protocol deviations will be reviewed as part of the ongoing data cleaning process and 
data evaluation. All important deviations will be identified and documented prior to database 
lock to confirm exclusion from analysis sets.
12.6
Handling of dropouts or missing data
There will be no special procedures for handling withdrawals and missing data.
12.7
Planned interim analysis and data monitoring
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of the first 20 subjects in Cohort 1 and after completion of 
the first 20 subjects in Cohort 2. 
12.7.1
Definition of stopping rules
No formal stopping rule will be applied. The DMC may give a recommendation to stop the study 
after reviewing the safety data as described in Section 12.7.2. A recommendation for stopping 
should be based on the collective experience of the DMC members. After meeting to review data 
from each cohort, the DMC will provide a recommendation in writing regarding whether to 
continue or to stop the study. UCB will consider this recommendation and ensure the study 
investigators are informed of the sponsor’s decision on how to continue as described below.
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
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Page 66 of 240
12.7.2
Data Monitoring Committee
The DMC members will be defined in the DMC charter. 
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion durations as follows:
 15 minutes but no longer than 30 minutes only in subjects who would directly benefit
from an increased infusion rate, in the opinion of the investigator; OR,
 30 minutes but no longer than 60 minutes in subjects who would not directly benefit
from an increased infusion rate, in the opinion of the investigator
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to receive 
iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a duration of
30 minutes but no longer than 60 minutes whenever possible.
After completion of the first 20 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion durations as follows: 
 15 minutes but no longer than 30 minutes only in subjects who would directly benefit
from an increased infusion rate, in the opinion of the investigator; OR,
 30 minutes but no longer than 60 minutes in subjects who would not directly benefit
from an increased infusion rate, in the opinion of the investigator
x OR approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 30 minutes but no longer than 60 minutes, 
x OR Cohort 2 should be stopped.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 67 of 240
12.8
Determination of sample size
Approximately 100 subjects will be enrolled, which includes up to 2 cohorts of at least 
40 subjects for Cohort 1 and approximately 44 subjects for Cohort 2. No formal sample size 
calculation has been performed. The sample size was deemed clinically appropriate for the 
evaluation of safety, tolerability, and PK of iv LCM administration in pediatric subjects with 
epilepsy. 
13
ETHICS AND REGULATORY REQUIREMENTS
13.1
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’s legal representative(s) in both oral and written form 
by the investigator (or designee). Subject’s legal representative(s) 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’s legal representative(s) and by the person who conducted the 
informed consent discussion (investigator or designee). The subject’s legal representative(s) 
must receive a copy of the signed and dated Informed Consent form. As part of the consent 
process, each subject’s legal representative(s) must consent to direct access to the subject’s 
medical records for study-related monitoring, auditing, IRB/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 IRB/IEC and use of the amended form.
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form.
The subject’s legal representative(s) may withdraw his/her consent to participate in the study at 
any time. A subject is considered as enrolled in the study when his/her legal representative(s) has 
signed the Informed Consent form. A CRF must not be started, nor may any study specific 
procedure be performed for a given subject, without having obtained written consent from
his/her legal representative(s) in order to participate in the study.
13.2
Subject identification cards
Upon signing the Informed Consent and Assent form (as applicable), the subject or legal 
representative 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.
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 68 of 240
13.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki.
The investigator/UCB will ensure that an appropriately constituted IRB/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, the investigator/UCB 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 IRB/IEC for its review and approval.
Before initiating a study, the investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol.
The investigator will also promptly report to the IRB/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 IRB/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 IRB/IEC as 
allowed.
As part of the IRB/IEC requirements for continuing review of approved studies, the investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of subject risk involved, but no less than 
once per year. The investigator should provide a final report to the IRB/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 IRB/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 the sponsor (or its representative) with evidence of such IRB/IEC 
notification.
13.4
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 
assigned at Screening.
The investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/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 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 69 of 240
admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study).
13.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
evaluations of sample size and the likelihood of the study fulfilling its primary objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented.
14
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 contract 
research organization agreements, as applicable.
15
REFERENCES
Aicardi J. Syndromic classification in the management of childhood epilepsy. J Child Neurol. 
1994;9(Suppl 2):14-18.
Appleton R, Fichtner K, LaMoreaux L, Alexander J, Halsall G, Murray G, et al. Gabapentin as 
add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, 
placebo-controlled study. Gabapentin Pediatric Study Group. Epilepsia. 1999;40:1147-54.
Arkilo D, Gustafson M, Ritter FJ. Clinical experience of intravenous lacosamide in infants and 
young children. Eur J Paediatr Neurol. 2016;20(2):212-7.
CDC growth curves. Girls: http://www.cdc.gov/growthcharts/data/set1clinical/cj41c022.pdf. 
Boys: http://www.cdc.gov/growthcharts/data/set1clinical/cj41c021.pdf. 2000. 
CHMP/EWP/566/98 Guideline on clinical investigation of medicinal products in the treatment of 
epileptic disorders (EMA) Rev 2, 20 Jan 2010.
CPMP/ICH/135/95 Note for guidance on Good Clinical Practice (EMEA) Jul 2002.
Columbia University Medical Center. Columbia-Suicide Severity Rating Scale (2008). 
http://www.cssrs.columbia.edu/. Accessed on 03 Jul 2014.
Commission on Classification and Terminology of the International League Against Epilepsy. 
Proposal for revised classification of epilepsies and epileptic syndromes. 
Epilepsia.1989;30:389-99.
Duchowny M, Pellock JM, Graf WD, Billard C, Gilman J, Casale E, et al. A placebo-controlled 
trial of lamotrigine add-on therapy for partial seizures in children. Lamictal Pediatric Partial 
Seizure Study Group. Neurology. 1999;53:1724-31.
Elterman RD, Glauser TA, Wyllie E, Reife R, Wu SC, Pledger G. A double-blind, randomized 
trial of topiramate as adjunctive therapy for partial-onset seizures in children. Topiramate YP 
Study Group. Neurology. 1999;52:1338-44.
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 70 of 240
Food and Drug Administration. Guidance for Industry. Drug-induced liver injury: premarketing 
clinical evaluation. US Dept of Health and Human Services, Center for Drug Evaluation and 
Research, Center for Biologics Evaluation and Research, 07/2009. 
Glauser TA, Ayala R, Elterman RD, Mitchell WG, Van Orman CB, Gauer LJ, et al. 
Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures. 
Neurology. 2006;66:1654-60.
Hadjiloizou SM, Bourgeois BF. Antiepileptic drug treatment in children. Expert Rev Neurother. 
2007;7:179-93.
Herman ST, Pedley TA. New options for the treatment of epilepsy. JAMA. 1998;280:693-4.
Institute of Medicine. Epilepsy across the spectrum: promoting health and understanding. 
Washington, DC: The National Academies Press; 2012.
Lamictal Pediatric Partial Seizure Study Group. Neurology. 1999;53:1724-31.
Ngugi AK, Kariuki SM, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Incidence of 
epilepsy: A systematic review and meta-analysis. Neurology. 2011; 77(10): 1005–12.
Perucca E. Established antiepileptic drugs. Baillieres Clin Neurol. 1996;5:693-722.
Rheims S, Ryvlin P. Profile of perampanel and its potential in the treatment of partial onset 
seizures. Neuropsychiatr Dis Treat. 2013;9:629-37.
Shorvon SD. Drug treatment of epilepsy in the century of the ILAE: the second 50 years, 
1959-2009. Epilepsia. 2009;50(Suppl 3):93-130.
Welsh SS, Lin N, Topjian AA, Abend NS. Safety of intravenous lacosamide in critically ill 
children. Seizure. 2017;52:76-80.
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Lacosamide
EP0060
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16
APPENDICES
16.1
Protocol Amendment 1
Rationale for the amendment
The primary purpose of this substantial amendment is to add further clarification regarding the 
design of the study, the definition of the clinical situation in which a subject will qualify for 
enrollment in this study, and to provide further clarification regarding the PK assessments in 
accordance with the US Food and Drug Administration (FDA) request. It is clarified that this 
study will enroll approximately 75 subjects ≥4 to <17 years of age and that another 
Phase 2/3 study is planned to investigate the use of iv LCM in subjects with epilepsy ≥1 month 
to <4 years of age. EP0060 will initially enroll older pediatric subjects (Cohort 1), which will 
include at least 20 subjects ≥12 to <17 years of age. After the first 10 subjects in each cohort 
have completed their iv LCM treatment over infusion durations of 30 to 60 minutes, the 
enrollment will be temporarily put on hold for the DMC to review the available safety and 
tolerability data. Based on their review, the DMC will recommend the target infusion duration to 
be used (30 minutes to 60 minutes or 15 to 30 minutes) for the remaining subjects in the cohort, 
whether the study/cohort should be stopped, and whether the next cohort can be initiated.
Additional changes have been implemented for consistency with other protocols in the LCM 
pediatric program.
Furthermore, administrative changes including the update of the study team and update of the 
Sponsor Declaration have been made.
At the time of approval of this amendment, no subjects were enrolled in EP0060.
Modifications and changes
Global changes
The following changes were made throughout the protocol:
x Text has been modified to clarify that approximately 75 subjects ≥4 to <17 years of age with 
epilepsy will be included in EP0060 and that another study is planned to investigate the use 
of iv LCM in subjects with epilepsy ≥1 month to <4 years of age.
x Text has been modified to allow an age staggered approach to enrollment. The enrollment 
will begin with the older pediatric subjects (Cohort 1: at least 20 subjects ≥12 to <17 years of 
age) followed sequentially by younger pediatric subjects (Cohort 2: at least 20 subjects ≥8 to
<12 years of age, and Cohort 3: at least 20 subjects ≥4 to <8 years of age). 
x Text has been modified to clarify that after completion of the first 10 subjects in each cohort, 
the enrollment will be temporarily put on hold for the DMC to review the available safety 
and tolerability data. Based on their review, the DMC will recommend the target infusion 
duration for the remaining subjects in the cohort, whether the study/cohort should be stopped, 
and whether the next cohort can be initiated.
x Inclusion Criterion #2 has been amended as diaries are not used in this study. 
x Inclusion Criterion #3 has been amended to clarify that subjects from ≥4 to <17 years of age 
can be enrolled in the study.
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 72 of 240
x Inclusion Criterion #4 has been deleted as it is no longer applicable based on the amended 
age of the subjects in the study. 
x Inclusion Criterion #5 (new numbering) has been added to clarify the clinical situation in 
which a subject will qualify for enrollment in this study.
x Inclusion Criterion #10 has been reworded to clarify the allowed use of prescribed oral 
VIMPAT depending on subject’s weight.
x Inclusion Criterion #11 has been reworded to clarify that intake of the prescribed total daily 
dose of prescribed oral VIMPAT must be confirmed for at least 3 days prior to first infusion.
x Inclusion Criterion #12 has been reworded to clarify requirements in case of concomitant 
AEDs.
x Exclusion Criterion #2 has been deleted as any subject expected to be hospitalized longer 
than 5 days may enter the study, but may not receive iv LCM in EP0060 longer than 5 days.
x Exclusion Criterion #8 (new numbering) has been revised to clarify that subjects who have a 
medical condition that could reasonably be expected to interfere with oral LCM absorption 
are not excluded from the study.
x Exclusion Criterion #11 (new numbering) has been amended to clarify that subjects are 
excluded from the study with creatinine clearance of less than 30mL/min. 
x Exclusion Criterion #18 has been deleted as vigabatrin is permitted during the study. 
x Exclusion Criterion #19 (new numbering) has been amended to specify that subjects with 
known cardiac sodium channelopathy are excluded from the study.
x Text has been modified to clarify the equation to be used to calculate the total volume of 
fluid according to the subject’s weight.
x Text has been modified regarding concomitant treatments so that subjects who have been 
treated with ethosuximide are not excluded from the study, treatment with vigabatrin or 
ethosuximide and with neuroleptics is allowed during the course of the study, any doses of 
anxiolytics or hypnotics are allowed for nonepilepsy indications, and use of benzodiazepines 
is not restricted.
x Text has been revised to clarify the procedures by visit; details of prior and concomitant 
medications recording; timing of the Telephone Contact assessments; morning or evening 
timing of some procedures during the study visits; and timing of infusion, blood sampling, 
vital signs, and ECG measurements; and to clarify the required subject positions during vital 
signs and ECG measurements.
x Text has been modified to indicate that the LCM metabolite SPM 12809 will also be 
analyzed. Furthermore, additional PK assessments may be obtained at the discretion of the 
investigator, especially in the event of a relevant treatment-emergent AE.
x Text has been revised to clarify actions in case of pregnancy.
x Text has been revised to clarify the version of the C-SSRS that needs to be completed by 
subjects who are ≥6 years of age.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 73 of 240
x The use of some terms has been revised: the terms “inpatient” and “BMI” have been deleted, 
and the terms “hospital” and “hospitalization” have been replaced with “health care facility” 
and “admission to the health care facility,” respectively, where appropriate.
x The Clinical Project Manager has been changed and contact details have been updated.
x The Sponsor Declaration has been updated as the protocol will be signed electronically.
x Other changes made in this amendment are to provide clarification, are administrative in 
nature, or are to correct errors. 
Specific changes
Change #1
Title page
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY AND 
TOLERABILITY OF INTRAVENOUS LACOSAMIDE AS REPLACEMENT FOR ORAL 
LACOSAMIDE IN CHILDREN (≥1 MONTH TO <17 YEARS OF AGE) WITH EPILEPSY
Has been changed to:
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY AND 
TOLERABILITY OF INTRAVENOUS LACOSAMIDE AS REPLACEMENT FOR ORAL 
LACOSAMIDE IN CHILDREN (≥4 TO <17 YEARS OF AGE) WITH EPILEPSY
Change #2
STUDY CONTACT INFORMATION
Clinical Project Manager
Name:
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Has been changed to:
Clinical Project Manager
Name:
Address:
UCB BIOSCIENCES, Inc.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 74 of 240
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Change #3
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA: +1 800 880 6949
Canada: +1 877 582 8842
Japan: +81 3 6864 7400
Email
Global: DS_ICT@ucb.com (for interventional clinical studies)
Japan: JDSO@ucb.com
Has been changed to:
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA: +1 800 880 6949
Canada: +1 877 582 8842
Email
Global: DS_ICT@ucb.com (for interventional clinical studies)
Change #4
LIST OF ABBREVIATIONS
BMI and CRO have been deleted and FDA has been added.
Change #5
Section 1 SUMMARY
EP0060 is a Phase 2/3, multicenter, open-label, inpatient study to evaluate the safety and 
tolerability of adjunctive intravenous (iv) lacosamide (LCM) infusions as replacement for oral 
LCM in pediatric subjects with epilepsy where the subject is currently taking oral LCM and 
needs to undergo a procedure, be admitted to an epilepsy monitoring unit (EMU) or hospital, or 
other situations where iv administration is clinically appropriate. Up to 75 subjects, who are 
participating in a long-term, open-label study with LCM (SP848, EP0034, EP0012, or other 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 75 of 240
future study) or who are currently prescribed VIMPAT® (LCM) will be enrolled. Pediatric 
subjects entering into EP0060 from a long-term, open-label study will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll directly 
into EP0060 will temporarily switch from their prescribed VIMPAT oral treatment to the iv 
LCM formulation. Subjects will be enrolled from approximately 40 sites in North America, 
Europe, Asia Pacific, and Latin America. Additional sites or regions may be added if deemed 
necessary.
The primary objective of EP0060 is to evaluate the safety and tolerability of iv LCM infusion(s)
administered over target durations of 30 minutes or 15 minutes in pediatric subjects ≥1 month to 
<17 years with epilepsy. 
EP0060 will be comprised of up to 3 cohorts. 
x Approximately 25 subjects will be enrolled into Cohort 1 in order to receive iv LCM, which 
should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of Cohort 1, enrollment into EP0060 will be temporarily put on hold to allow 
for a Data Monitoring Committee (DMC) review of the safety and tolerability data from 
Cohort 1. Based on the review of the Cohort 1 data, the DMC will make a recommendation for 
the target infusion duration to be evaluated in Cohort 2. 
x EITHER approximately 25 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible,
x OR approximately 25 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible. 
The DMC will reconvene after the completion of Cohort 2. If the Cohort 2 target infusion 
duration was 30 minutes but no longer than 60 minutes, enrollment into the study will be stopped 
once Cohort 2 has completed. If the Cohort 2 target infusion duration was 15 but no longer than 
30 minutes, the DMC will make a recommendation for the target infusion duration to be 
evaluated in Cohort 3.
x EITHER approximately 25 additional subjects will be enrolled into Cohort 3 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 25 additional subjects will be enrolled into Cohort 3 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible. 
After completion of Cohort 3, the DMC will reconvene to review the final data to provide their 
overall impression.
This design will result in a total exposure of at least approximately 50 pediatric subjects (up to 
75 pediatric subjects) to assess the safety of iv LCM administered over a range of infusion 
durations.
EP0060 is comprised of the following: Screening and/or Baseline Period (up to 7 days); 
Treatment Period (up to 5 days); an End-of-Study/Final Visit (1 day); and a Follow-Up
Period/Telephone Contact (up to 2 days). During the Screening Period (Day -1), oral LCM 
tablets will be administered in accordance with each subject’s oral LCM dosage regimen. During 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 76 of 240
the Treatment Period, subjects will receive iv LCM infusion twice daily (bid) at approximately 
12-hour intervals. The daily dose of iv LCM will be the same as the subject's current stable daily 
dose of oral LCM (2 to 12mg/kg/day or 100 to 600mg/day). During the Treatment Period, blood 
samples will be obtained for pharmacokinetic (PK) analysis, and safety assessments will be 
collected (physical and neurological exams, pulse rate, blood pressure, and 12-lead 
electrocardiogram [ECG]). An End-of-Study/Final Visit will be conducted the day after the last 
dose of iv LCM after completion of or withdrawal from the Treatment Period. A safety 
follow-up assessment will be collected during the Follow-Up Period by phone or in person, 1 to
2 days after the last dose of iv LCM in the Treatment Period. 
The maximum study duration for an individual subject will be approximately 15 days. After 
completion of or discontinuation from EP0060, only subjects who enrolled into EP0060 from a 
long-term, open-label study will resume their participation in that study and resume oral LCM 
treatment accordingly. Subjects who were prescribed VIMPAT should continue antiepileptic 
drug (AED) treatment at the discretion of the treating physician.
Has been changed to:
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of 
intravenous (iv) lacosamide (LCM) infusions as replacement for oral LCM in pediatric subjects 
≥4 to <17 years of age with epilepsy. A separate Phase 2/3 study investigating the use of iv LCM 
as replacement for oral LCM therapy in pediatric subjects with epilepsy ≥1 month to <4 years of 
age is planned. EP0060 will include subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) who need to undergo a procedure, be 
admitted to an epilepsy monitoring unit (EMU) or health care facility, or other situations where 
iv administration is clinically appropriate. Approximately 75 subjects, who are participating in a 
long-term, open-label study with LCM (SP848, EP0034, EP0012, or other future study) or who 
are currently prescribed VIMPAT® (LCM) will be enrolled. Pediatric subjects entering into 
EP0060 from a long-term, open-label study will temporarily suspend their participation in that 
study to receive iv LCM treatment in EP0060. Subjects who enroll directly into EP0060 will 
temporarily switch from their prescribed VIMPAT oral treatment to the iv LCM formulation. 
Subjects will be enrolled from approximately 40 sites in North America, Europe, Asia Pacific, 
and Latin America. Additional sites or regions may be added if deemed necessary.
The primary objective of EP0060 is to evaluate the safety and tolerability of iv LCM infusion(s)
in pediatric subjects ≥4 to <17 years with epilepsy, after temporarily switching from the 
equivalent stable oral LCM dose. EP0060 is planned to include up to 3 age-based cohorts of at 
least 20 subjects per cohort: ≥12 to <17 years (Cohort 1), ≥8 to <12 years (Cohort 2), and ≥4 to 
<8 years (Cohort 3). A Data Monitoring Committee (DMC) will review the safety and 
tolerability data for each cohort to make recommendations for the progression of subsequent 
cohort enrollment and iv infusion durations to be evaluated. 
EP0060 is comprised of the following study periods: 
x Screening and/or Baseline Period (up to 7 days),
x Treatment Period (up to 5 days),
x End-of-Study/Final Visit (1 day), 
x End-of-Study/Telephone Contact (1 to 2 days). 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 77 of 240
During the Screening Period (Day -7 to Day -1), oral LCM will be administered in accordance 
with each subject’s oral LCM dosage regimen. During the Treatment Period, subjects will 
receive iv LCM infusions twice daily (bid) at approximately 12-hour intervals for up to 5 days. 
The daily dose of iv LCM will be the same as the subject's current stable daily dose of oral LCM 
(2 to 12mg/kg/day or 100 to 600mg/day). During the Treatment Period, blood samples will be 
obtained for pharmacokinetic (PK) analysis, and detailed safety assessments will be performed. 
An End-of-Study/Final Visit will be conducted the day after the last dose of iv LCM after 
completion of or withdrawal from the Treatment Period. A safety follow-up Telephone Contact 
should occur 1 to 2 days after the End-of-Study/Final Visit. 
The maximum study duration for an individual subject will be approximately 15 days. After 
completion of or discontinuation from EP0060, only subjects who enrolled into EP0060 from a 
long-term, open-label study will resume their participation in that study and resume oral LCM 
treatment accordingly. Subjects who were prescribed VIMPAT should continue antiepileptic 
drug (AED) treatment at the discretion of the treating physician.
EP0060 will begin with Cohort 1, where at least 20 subjects ≥12 to <17 years of age will be 
enrolled to receive iv LCM. For the first 10 subjects in Cohort 1, iv LCM should be infused over 
a duration of 30 minutes but no longer than 60 minutes whenever possible. 
After completion of the first 10 subjects in Cohort 1, enrollment into Cohort 1 will be 
temporarily put on hold to allow for the DMC review of the safety and tolerability data from 
these subjects. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥8 to <12 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, enrollment into Cohort 2 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1 and Cohort 2. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 2 should be stopped, 
x AND whether Cohort 3 can be initiated.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 78 of 240
For Cohort 3, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 3, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 3, enrollment into Cohort 3 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1, Cohort 2, and Cohort 3. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 3 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 3 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 3 should be stopped, 
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations.
Change #6
Section 2 INTRODUCTION, last paragraph
The results of EP0060 will provide safety and PK data regarding the use of the iv LCM 
formulation in pediatric subjects ≥1 month to <17 years with epilepsy.
Has been changed to:
The results of EP0060 will provide safety, tolerability, and PK data regarding the use of the 
iv LCM formulation as replacement for oral LCM in pediatric subjects ≥4 to <17 years with
epilepsy.
Change #7
Section 3 STUDY OBJECTIVE(S)
The primary objective of this study is to evaluate the safety and tolerability of adjunctive iv LCM 
infusion(s) in pediatric subjects ≥1 month to <17 years with epilepsy, after temporarily switching 
from the equivalent stable oral LCM dose. An additional objective is to evaluate the PK of 
iv LCM in pediatric subjects with epilepsy.
Has been changed to:
The primary objective of this study is to evaluate the safety and tolerability of iv LCM 
infusion(s) in pediatric subjects ≥4 to <17 years with epilepsy, after temporarily switching from 
the equivalent stable oral LCM dose. An additional objective is to evaluate the PK of iv LCM 
replacement in pediatric subjects with epilepsy.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 79 of 240
Change #8
Section 4.2 Pharmacokinetic variable(s)
The PK variables will include plasma concentration of LCM and its metabolite, SPM12809. 
Has been changed to:
The PK variables will include plasma concentration of LCM and its main metabolite, 
SPM 12809.
Change #9
Section 5.1 Study description 
EP0060 is a Phase 2/3, multicenter, open-label, inpatient study to evaluate the safety and 
tolerability of adjunctive iv LCM infusions as replacement for oral LCM in pediatric subjects 
with epilepsy where the subject is currently taking oral LCM and needs to undergo a procedure, 
be admitted to an EMU or hospital, or other situations where iv administration is clinically 
appropriate. Up to approximately 75 subjects, who are participating in long-term, open-label 
studies with LCM or who are currently prescribed VIMPAT, will be enrolled. Pediatric subjects 
entering into EP0060 from a long-term, open-label study will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll directly 
into EP0060 will temporarily switch from their prescribed oral VIMPAT treatment to the 
iv LCM formulation. Subjects will not be prescribed or maintained on VIMPAT for the purposes 
of participating in EP0060. Subjects will be enrolled from approximately 40 sites in North
America, Europe, Asia Pacific, and Latin America. Additional sites or regions may be added if 
deemed necessary.
EP0060 will be comprised of up to 3 cohorts. 
x Approximately 25 subjects will be enrolled into Cohort 1 in order to receive iv LCM, which 
should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of Cohort 1, enrollment into EP0060 will be temporarily put on hold to allow 
for a Data Monitoring Committee (DMC) review of the safety and tolerability data from 
Cohort 1. Based on the review of the Cohort 1 data, the DMC will make a recommendation for 
the target infusion duration to be evaluated in Cohort 2. 
x EITHER approximately 25 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 25 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible. 
The DMC will reconvene after the completion of Cohort 2. If the Cohort 2 target infusion 
duration was 30 minutes but no longer than 60 minutes, enrollment into the study will be stopped 
once Cohort 2 has completed. If the Cohort 2 target infusion duration was 15 but no longer than 
30 minutes, the DMC will make a recommendation for the target infusion duration to be 
evaluated in Cohort 3.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 80 of 240
x EITHER approximately 25 additional subjects will be enrolled into Cohort 3 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 25 additional subjects will be enrolled into Cohort 3 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible. 
After completion of Cohort 3, the DMC will reconvene to review the final data to provide their 
overall impression.
This design will result in a total exposure of approximately 50 pediatric subjects (up to 
approximately 75 pediatric subjects) to assess the safety of iv LCM administered over a range of 
infusion durations. 
EP0060 is comprised of the following: Screening and/or Baseline Period (up to 7 days); 
Treatment Period (up to 5 days); an End of Study/Final Visit (1 day); and a Follow-Up
Period/Telephone Contact (up to 2 days). During the Screening Period (Day -1), oral LCM 
tablets will be administered in accordance with each subject’s LCM dosage regimen. For 
subjects enrolled in a long-term, open-label study, the oral LCM will be administered from the 
long-term, open-label study supply. For subjects prescribed VIMPAT and enrolling directly into 
EP0060, oral LCM will be administered from the subject’s prescribed VIMPAT supply. 
Subjects will be under medical care at a healthcare facility for the duration of the iv LCM 
infusion treatment in EP0060. If necessary, the Screening and/or Baseline Visit can occur on the 
same day as the first iv LCM infusion. In both cases, it is required that all screening procedures 
are performed and the results of examinations (ie, ECG) are available to allow verification of 
subject eligibility. During the Treatment Period, subjects will receive iv LCM infusion twice 
daily (bid) at 12-hour intervals. The daily dose of iv LCM will be the same as the subject's 
current stable daily dose of oral LCM (2 to 12mg/kg/day or 100 to 600mg/day). During the 
Treatment Period, blood samples will be obtained for pharmacokinetic (PK) analysis, and safety 
assessments will be collected (physical and neurological exams, pulse rate, blood pressure, and 
12-lead ECG). An End-of-Study/Final Visit will be conducted the day after the last dose of 
iv LCM after completion of or withdrawal from the Treatment Period. A safety follow-up
assessment will be collected during the Follow-Up Period by telephone or in person 1 to 2 days 
after the last dose of iv LCM in the Treatment Period.
The maximum study duration for an individual subject will be approximately 15 days. After 
completion of or discontinuation from EP0060, subjects who enrolled into EP0060 from a 
long-term, open-label study will resume their participation in that study and resume oral LCM 
treatment accordingly. Subjects who were prescribed VIMPAT should continue AED treatment 
at the discretion of the treating physician.
The schedule of study assessments is provided in Section 5.2.
Has been changed to:
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of iv 
LCM infusions as replacement for oral LCM in pediatric subjects ≥4 to <17 years of age with 
epilepsy. EP0060 will include subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) who need to undergo a procedure, be 
admitted to an EMU or health care facility, or other situations where iv administration is 
clinically appropriate. Approximately 75 subjects, who are participating in long-term, open-label 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 81 of 240
studies with LCM or who are currently prescribed VIMPAT, will be enrolled. Pediatric subjects 
entering into EP0060 from a long-term, open-label study will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll directly 
into EP0060 will temporarily switch from their prescribed oral VIMPAT treatment to the iv 
LCM formulation. Subjects will not be prescribed or maintained on VIMPAT for the purposes of 
participating in EP0060. Subjects will be enrolled from approximately 40 sites in North America, 
Europe, Asia Pacific, and Latin America. Additional sites or regions may be added if deemed 
necessary.
EP0060 is planned to include up to 3 age-based cohorts of at least 20 subjects per cohort: ≥12 to 
<17 years (Cohort 1), ≥8 to <12 years (Cohort 2), and ≥4 to <8 years (Cohort 3). A DMC will 
review the safety and tolerability data for each cohort to make recommendations for the 
progression of subsequent cohort enrollment and iv infusion durations to be evaluated. Details 
regarding the DMC are provided in Section 12.7.2.
EP0060 is comprised of the following study periods: 
x Screening and/or Baseline Period (up to 7 days),
x Treatment Period (up to 5 days),
x End-of-Study/Final Visit (1 day), 
x End-of-Study/Telephone Contact (1 to 2 days). 
During the Screening Period (Day -7 to Day -1), oral LCM will be administered in accordance 
with each subject’s oral LCM dosage regimen. For subjects enrolled in a long-term, open-label 
study, the oral LCM will be administered from the long-term, open-label study supply. For 
subjects prescribed VIMPAT and enrolling directly into EP0060, oral LCM will be administered 
from the subject’s prescribed VIMPAT supply. 
Subjects will be under medical care at a healthcare facility for the duration of the iv LCM 
infusion treatment in EP0060. If necessary, the Screening and/or Baseline Visit can occur on the 
same day as the first iv LCM infusion. In this case, it is required that all screening procedures are 
performed and the results of examinations (ie, ECG) are available to allow verification of subject 
eligibility. During the Treatment Period, subjects will receive iv LCM infusion bid at 
approximately 12-hour intervals for up to 5 days. The daily dose of iv LCM will be the same as 
the subject's current stable bid dose of oral LCM (2 to 12mg/kg/day or 100 to 600mg/day). 
During the Treatment Period, blood samples will be obtained for PK analysis, and safety 
assessments will be performed (physical and neurological exams, pulse rate, BP, 12-lead ECG, 
clinical hematology and chemistry, and Columbia-Suicide Severity Rating Scale [C-SSRS] when 
applicable). An End-of-Study/Final Visit will be conducted the day after the last dose of iv LCM 
after completion of or withdrawal from the Treatment Period. A safety follow-up Telephone 
Contact should occur 1 to 2 days after the End-of-Study/Final Visit.
The maximum study duration for an individual subject will be approximately 15 days. After 
completion of or discontinuation from EP0060, subjects who enrolled into EP0060 from a 
long-term, open-label study will resume their participation in that study and resume oral LCM 
treatment accordingly. Subjects who were prescribed VIMPAT should continue AED treatment 
at the discretion of the treating physician.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 82 of 240
The schedule of study assessments is provided in Section 5.2.
EP0060 will begin with Cohort 1, where at least 20 subjects ≥12 to <17 years of age will be 
enrolled to receive iv LCM. For the first 10 subjects in Cohort 1, iv LCM should be infused over 
a duration of 30 minutes but no longer than 60 minutes whenever possible. 
After completion of the first 10 subjects in Cohort 1, enrollment into Cohort 1 will be 
temporarily put on hold to allow for the DMC review of the safety and tolerability data from 
these subjects. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥8 to <12 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, enrollment into Cohort 2 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1 and Cohort 2. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 2 should be stopped, 
x AND whether Cohort 3 can be initiated.
For Cohort 3, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 3, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 3, enrollment into Cohort 3 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1, Cohort 2, and Cohort 3. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 3 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 3 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 3 should be stopped, 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 83 of 240
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age). 
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations.
Change #10
Section 5.1.1 Study duration per subject
The maximum iv LCM exposure per subject will be up to 5 days with a total study duration of up 
to 15 days (up to 7 days for screening, up to 5 days of treatment, 1 day for discharge/Final Visit, 
and Telephone Contact/Follow-Up up to 2 days after last dose of iv LCM.
The end of the study is defined as the date of the last contact of the last subject in the study.
Has been changed to:
The maximum iv LCM exposure per subject will be up to 5 days with a total study duration of up 
to 15 days (up to 7 days for screening, up to 5 days of treatment, 1 day for discharge/Final Visit, 
and a safety follow-up Telephone Contact 1 to 2 days after the Final Visit).
The end of the study is defined as the date of the last contact of the last subject in the study.
Change #11
Section 5.1.2 Planned number of subjects and site(s)
Up to 75 subjects currently participating in long-term, open-label studies with LCM or who are 
currently prescribed VIMPAT will be enrolled at approximately 40 sites. 
In each cohort, the following target number of subjects will be enrolled in each age group:
x At least 4 subjects ≥1 month to <4 years of age
x At least 4 subjects ≥4 to <8 years of age
x At least 4 subjects ≥8 to <12 years of age
x At least 4 subjects ≥12 to ≤16 years of age 
In total, across all cohorts, at least 8 subjects (for a 2-cohort study) or 12 subjects (for a 3-cohort 
study) will be enrolled in each age group.
Has been changed to:
Approximately 75 subjects currently participating in long-term, open-label studies with LCM or 
who are currently prescribed VIMPAT will be enrolled at approximately 40 sites.
The following cohorts are planned:
x Cohort 1: at least 20 subjects from ≥12 to <17 years of age
x Cohort 2: at least 20 subjects from ≥8 to <12 years of age
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 84 of 240
x Cohort 3: at least 20 subjects from ≥4 to <8 years of age 
The remaining subjects may be enrolled in any of the 3 cohorts.
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 85 of 240
Change #12
Section 5.2 Table 5-1: Schedule of study assessments
Table 5-1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitb
End-of-Study Period
Visit
V1a
V1ba
V2
V3
Final Visitc
TCd
Study Day
-7
to -1
-1
1
2 - 5
2 - 6
2 - 9
AM
PM
AM
PM
Written informed consent
X
Inclusion/exclusion criteria
X
Xe
X
X
Demographics
X
Medical procedures
X
Procedure historyf
X
Medical history/updatef
X
Diagnosis of epilepsyf
X
Childbearing potentialf
X
LCM dosing historyg
X
Prior and concomitant medicationsh
X
X
X
X
X
X
X
X
X
Concomitant AEDs/VNS settings 
X
X
X
X
X
X
X
X
Pregnancy testingi
X
X
Withdrawal criteria
X
X
X
X
X
X
AE reportingj
X
X
X
X
X
X
X
X
X
ILAE seizure classification 
X
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 86 of 240
Physical examination (complete)
X
X
Table 5-1:
Schedule of study assessments (continued)
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitb
End of Study Period
Visit
V1a
V1ba
V2
V3
Final Visitc
TCd
Days in study
-7
to -1
-1
1
2 - 5
2 - 6
2 - 7
AM
PM
AM
PM
Neurological examination (complete)
X
X
Clinical chemistry and hematologyk
X
X
X
X
12-lead ECG
X
Xl
Xl
Xl
Xl
Xl
X
X
Vital signs
X
Xl
Xl
Xl
Xl
Xl
X
X
Body weight, height, and BMI
X
Blood sample for LCM PKm
X
X
X
X
X
Admission to the unitn
X
X
Oral LCM administrationo
X
X
X
X
Intravenous LCM infusion
X
X
X
X
X
C-SSRSp
X
Xq
X
X
Xb
X
Signs and symptoms of depression
X
X
X
X
X
X
X
X
Discharge from the unit
X
AE=adverse event; AED=antiepileptic drug; BMI=body mass index; BP=blood pressure; C-SSRS=Columbia-Suicide Severity Rating Scale; 
ECG=electrocardiogram; ILAE=International League against Epilepsy; iv=intravenous; LCM=lacosamide; PK=pharmacokinetics; TC=Telephone Contact; 
V=Visit; VNS=vagus nerve stimulation
a Visit 1b only applies when Screening and Baseline occur on separate days. 
b If an Unscheduled Visit is needed, the assessments noted will be performed. Additional assessments can be performed at the investigator’s discretion. The 
C-SSRS assessment should be completed if the Unscheduled Visit is due to an AE.
c A Final Visit must be completed the day after the last dose of iv LCM for all subjects who complete or withdraw prematurely from EP0060. For subjects 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 87 of 240
who will discontinue use of LCM, the subject should complete the EP0060 Final Visit and refer to the long-term, open-label studies taper regimen.
d The Telephone Contact assessment should be performed 1 to 2 days after the last dose of iv LCM in the Treatment Period during the Follow-Up Period (2 
to 7 days after Visit 2/Day 1). During the contact, the site should inquire as to whether the subject noted any change at the site of the infusion.
e Verification that the subject continues to meet inclusion/exclusion criteria if Screening and Baseline occur on separate days.
f Procedure history, medical history, diagnosis of epilepsy, and childbearing potential will be collected for direct-enroll subjects who were prescribed 
VIMPAT prior to entering the study. Medical history update will be collected for subjects from the long-term open-label studies. 
g Lacosamide dosing history will include date, time, and quantity during the last 3 days.
h Prior medications will only be collected for direct-enroll subjects. Concomitant medications from the long-term open-label studies will be followed, as well 
as the recording of new concomitant medications during EP0060.
i Pregnancy testing for subjects of childbearing potential will be serum testing at the Screening Visit for direct-enroll subjects who are prescribed VIMPAT 
and urine testing for subjects enrolled in long-term, open-label studies. Urine pregnancy testing (or serum pregnancy test if no urine sample can be 
obtained) will be conducted on all subjects of childbearing potential at the Final Visit. 
j Ongoing AEs from the long-term open-label studies will be followed, as well as recording of new AEs during EP0060. 
k Laboratory assessments will be performed for subjects who are directly enrolled into EP0060. Screening laboratory assessments may be conducted up to 
the day of the infusion provided they are reviewed and meet inclusion/exclusion criteria prior to the infusion.
l Vital Signs will be performed 5 minutes prior to infusion and at 5, 10, 20, 45, 60 minutes, and 2 hours from the start of each iv administration. Noninvasive 
BP (systolic and diastolic) and pulse rate will be measured at study visits in a sitting position after at least 3 minutes at rest, when feasible. 12-lead ECG 
will be performed 5 minutes prior to infusion and at 15, 30, 60 minutes, and 2 hours from the start of each iv administration. Care should be taken to assure 
proper lead placement and quality ECG recordings. Subjects should rest in a supine position at least 5 minutes prior to each ECG recording and should be 
motionless during the recording.
m Samples for PK will be drawn after ECG and vital signs have been taken on Day 1 (within 1 hour prior to the first iv LCM dose and 1 to 4 hours after the 
second iv LCM dose) and on the Final Treatment Visit (within 1 hour prior to the first iv LCM dose and 1 to 4 hours after the second iv LCM dose) from 
the opposite arm in which the solution for infusion was administered.
n Admission to the hospital to participate in the study should take place at least the day prior to the start of the first iv LCM infusion. However, when 
necessary for the wellbeing of the subject or when the investigator deems it appropriate, the hospitalization and the first iv LCM infusion can start on the 
same day.
o On Day -1, oral LCM will be administered in accordance with each subject’s LCM dosage regimen. 
p For all subjects ≥6 years of age, the “since last visit” version of the C-SSRS assessment should be completed for all visits after the initial 
(Screening/Baseline) assessment. Signs and symptoms of depression for patients <6 years of age will also be assessed whenever a C-SSRS assessment is 
performed.
q The C-SSRS assessment (see Section 10.1.1.1) does not need to be completed twice if Screening/Baseline assessments are done on the same day.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 88 of 240
Table 5-1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitc
End-of-Study Period
Visit
V1a
V1ba
V2
V3b
Final Visitd
TCe
Study Day
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1
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2 to 6
2 to 9
Written informed consent
X
Inclusion/exclusion criteria
X
Xf
Demographics
X
Medical procedures
X
X
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X
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Procedure historyg
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Medical history/updateg
X
X
X
X
X
X
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Diagnosis of epilepsyg
X
Childbearing potentialg
X
LCM dosing historyh
X
Prior and concomitant medicationsi
X
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X
X
X
X
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Concomitant AEDs/VNS settings 
X
X
X
X
X
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Pregnancy testingj
X
X
Withdrawal criteria
X
X
X
X
X
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AE reportingk
X
X
X
X
X
X
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ILAE seizure classification 
X
Physical examination (complete)
X
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Neurological examination (complete)
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Clinical chemistry and hematologyl
X
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 89 of 240
Table 5-1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitc
End-of-Study Period
Visit
V1a
V1ba
V2
V3b
Final Visitd
TCe
Study Day
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2 to 6
2 to 9
12-lead ECG
X
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Vital signs
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Xn
Xn
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Body weight and height
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PK blood samplingo
X
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Admission to the unitp
X
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Oral LCM administrationq
X
X
X
X
Intravenous LCM infusionr
X
X
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C-SSRSs
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Xc
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Discharge from the unit
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AE=adverse event; AED=antiepileptic drug; BP=blood pressure; C-SSRS=Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; 
ILAE=International League against Epilepsy; iv=intravenous; LCM=lacosamide; PK=pharmacokinetics; TC=Telephone Contact; V=Visit; VNS=vagus 
nerve stimulation
a Visit 1b only applies when Screening and Baseline occur on separate days. 
b If iv LCM treatment is continued after Day 1, assessments for Visit 3 must be completed each day of iv LCM treatment in EP0060. 
c If an Unscheduled Visit is needed, the assessments noted will be performed. Additional assessments can be performed at the investigator’s discretion. The 
C-SSRS assessment should be completed if the Unscheduled Visit is due to an AE.
d A Final Visit must be completed the day after the last dose of iv LCM for all subjects who complete or withdraw prematurely from EP0060. For subjects 
who will discontinue use of LCM, the subject should complete the EP0060 Final Visit and refer to the long-term, open-label studies taper regimen.
e The Telephone Contact assessment should be performed 1 to 2 days after the Final Visit (2 to 7 days after Visit 2/Day 1). During the contact, the site 
should inquire as to whether the subject noted any change at the site of the infusion.
f Verification that the subject continues to meet inclusion/exclusion criteria if Screening and Baseline occur on separate days.
g Procedure history, medical history, diagnosis of epilepsy, and childbearing potential will be collected for direct-enroll subjects who were prescribed 
VIMPAT prior to entering the study. Medical history update will be collected for subjects from the long-term open-label studies. 
h Lacosamide dosing history will include date, time, and dosage information during the last 3 days.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 90 of 240
Table 5-1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitc
End-of-Study Period
Visit
V1a
V1ba
V2
V3b
Final Visitd
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Study Day
-7 to -1
-1
1
2 to 5
2 to 6
2 to 9
i Prior medications will only be collected for direct-enroll subjects. Concomitant medications from the long-term open-label studies will be followed, as well 
as the recording of new concomitant medications during EP0060 for all enrolled subjects.
j Pregnancy testing for subjects of childbearing potential will be serum testing at the Screening Visit for direct-enroll subjects who are prescribed VIMPAT 
and urine testing for subjects enrolled in long-term, open-label studies. Urine pregnancy testing (or serum pregnancy test if no urine sample can be 
obtained) will be conducted on all subjects of childbearing potential at the Final Visit. 
k Ongoing AEs from the long-term open-label studies will be followed, as well as recording of new AEs during EP0060. 
l Laboratory assessments will be performed for subjects who are directly enrolled into EP0060. Screening laboratory assessments may be conducted up to 
the day of the infusion provided they are reviewed and meet inclusion/exclusion criteria prior to the infusion.
m 12-lead ECG will be performed approximately 20 minutes prior to each infusion and at approximately 15, 30, 60 minutes, and 2 hours from the start of 
each iv administration. Care should be taken to assure proper lead placement and quality ECG recordings. Subjects should be at rest at least 5 minutes prior 
to each ECG recording and should be motionless during the recording, when feasible.
n Vital signs will be performed approximately 10 minutes prior to each infusion and at approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of 
each iv administration. Noninvasive BP (systolic and diastolic) and pulse rate will be measured at study visits after at least 3 minutes at rest, when feasible.
o Samples for PK will be drawn after ECG and vital signs have been taken. Plasma samples will be obtained from the opposite arm in which the solution for 
infusion was administered for the first iv LCM infusion (Day 1): predose (within 1 hour prior to iv LCM infusion) and postdose (within 1 to 4 hours after 
end of iv LCM infusion), and for the final iv LCM infusion (Day 2 to 5/Early Termination): predose (within 1 hour prior to iv LCM infusion) and postdose 
(within 1 to 4 hours after end of iv LCM infusion). Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in 
the event of a relevant treatment-emergent AE.
p Admission to the health care facility to participate in the study should take place at least the day prior to the start of the first iv LCM infusion. However, 
when necessary for the wellbeing of the subject or when the investigator deems it appropriate, the admission to the health care facility and the first iv LCM 
infusion can start on the same day.
q On Day -1, oral LCM will be administered in accordance with each subject’s LCM dosage regimen. 
r LCM will be administered twice daily at approximately 12-hour intervals, once in the morning and once in the evening, for up to 5 days.
s All subjects ≥6 years of age will complete the “Baseline/Screening” version of the C-SSRS at Visit 1 and will complete the “Since Last Visit” version at 
subsequent visits. If a subject becomes 6 years of age during the study, the "Already Enrolled" version of the C-SSRS should be used at the first visit at 
which the subject is 6 years of age and the “Since Last Visit” version used at subsequent visits. 
t The C-SSRS assessment (see Section 10.7.5) does not need to be completed twice if Screening/Baseline assessments are done on the same day.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 91 of 240
Change #13
Section 5.2 Table 5-2: Timing of infusion, blood sampling, and measurement of vital signs and ECG on Treatment Days 
(Infusion Day 1 to Day 5)
Table 5-2:
Timing of infusion, blood sampling, and measurement of vital signs and ECG on Treatment Days 
(Infusion Day 1 to Day 5)
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stopped (if prematurely terminated).
b T12 will be approximately 12 hours after T0.
c Pulse rate and blood pressure will be taken predose and post dose at least once daily, where clinically appropriate.
d Samples for PK will be drawn after ECG and vital signs have been taken on Day 1 (within 1 hour prior to the first iv LCM dose and 1 to 4 hours after the 
second iv LCM dose) and on the Final Treatment Visit (within 1 hour prior to the first iv LCM dose and 1 to 4 hours after the second iv LCM dose) from the 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 92 of 240
Has been changed to:
Table 5-2:
Timing of infusion, blood sampling, and measurement of vital signs 
and ECG on Treatment Days (Infusion Day 1 to Day 5)
Approximate time points referred to 
iv infusion 
Vital signsa
12-lead 
ECGb
PK blood samplingc
-59min to -3min
X
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T0 (start of infusion)
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min=minutes; PK=pharmacokinetics; T=time
a Noninvasive BP (systolic and diastolic) and pulse rate will be measured after at least 3 minutes at rest, when 
feasible, at the indicated approximate time points before and after the start of each iv LCM infusion.
b A 12-lead ECG will be performed at the indicated approximate time points before and after the start of each iv 
LCM infusion. Care should be taken to assure proper lead placement and quality ECG recordings. Subjects should 
be at rest at least 5 minutes prior to each ECG recording and should be motionless during the recording, when 
feasible.
c Samples for PK will be drawn after ECG and vital signs have been taken. Plasma samples will be obtained from 
the opposite arm in which the solution for infusion was administered for the first iv LCM infusion (Day 1) and the 
final iv LCM infusion (Day 2 to 5/Early Termination), predose and postdose, at the time points indicated in the 
table. Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in the 
event of a relevant treatment-emergent AE. Depending on the target duration defined for the cohort and subject 
tolerability, end of infusion can be at 15, 30, or 60 minutes, or whenever the infusion is stopped (if prematurely 
terminated).
d Time points are in reference to T0 (start of infusion) except the postdose PK sample, which should be obtained 
within 1 to 4 hours after the end of the iv LCM infusion.
Change #14
Section 5.3 Rationale for study design and selection of dose
EP0060 is an open-label, multicenter, inpatient study to investigate the safety and tolerability of 
adjunctive iv LCM as replacement for oral LCM therapy in pediatric subjects with epilepsy aged 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 93 of 240
≥1 month to <17 years. The results of EP0060 will provide safety and PK data regarding the use 
of the iv LCM formulation in pediatric subjects. The EP0060 design is based on the study design 
for SP757, which evaluated iv LCM replacement in adults with partial-onset seizures, as well as 
based on design elements of other pediatric iv AED studies.
The iv LCM formulation is approved at doses of 200 to 400mg/day as adjunctive therapy in the 
treatment of partial-onset seizures in subjects ≥16 years of age (depending on country-specific 
labeling) with epilepsy when oral administration is temporarily not feasible. 
A weight-based LCM dosing scheme for pediatric subjects is being evaluated in Phase 3 
double-blinded, placebo-controlled studies and targets similar LCM plasma concentrations as 
those observed in adults given 400mg/day. As such, the target doses of LCM for the Phase 3 
studies are 8 to 12mg/kg/day; however, subjects entering EP0060 can be on a wider range of 
LCM doses based on the ranges of doses allowed in the long-term, open-label studies (2 to 
12mg/kg/day or 100 to 600mg/day). Thus, the iv LCM doses being evaluated in EP0060 will 
range from 2 to 12mg/kg/day or 100 to 600mg/day for subjects enrolling from the long-term 
open-label studies and for subjects currently prescribed VIMPAT and enrolling directly into 
EP0060. 
The planned pediatric iv LCM labeling will be consistent with the approved adult iv LCM 
labeling and will also include infusion durations of 15 to 60 minutes depending on the evaluation 
of iv LCM PK, safety, and tolerability in pediatric subjects enrolled into EP0060. EP0060 will be 
comprised of up to 3 cohorts, and will first evaluate a target infusion duration of 30 minutes but 
no longer than 60 minutes whenever possible (Cohort 1). After a DMC review of the safety and 
tolerability data from subjects in Cohort 1, the DMC will make a recommendation for the target 
infusion duration to be evaluated in Cohort 2: EITHER 15 minutes but no longer than 30 minutes 
whenever possible, OR 30 minutes but no longer than 60 minutes whenever possible. If the 30 to 
60 minutes infusion duration is repeated, enrollment into the study will be stopped once Cohort 2 
has completed. If the Cohort 2 infusion is initiated at 15 to 30 minutes duration, the DMC will 
either recommend further evaluation at the 15 to 30 minutes infusion duration in Cohort 3, or to 
repeat evaluation of the 30 to 60 minutes infusion duration in Cohort 3. After completion of the 
enrollment of approximately 25 subjects in Cohort 3, the DMC will reconvene to review the final 
data to provide their overall impression.
This design will result in a total exposure of at least 50 pediatric subjects (up to 75 pediatric 
subjects) to assess the safety of iv LCM administered over a range of infusion durations. Taken 
together, the iv LCM dosing scheme and planned target infusion durations being evaluated in
EP0060 (2 to 12mg/kg/day or 100 to 600mg/day; 15 to 60 minutes) allow for administration of a 
range of pediatric doses at infusion durations that are the same as those approved for adults and 
adolescents.
Has been changed to:
EP0060 is an open-label, multicenter study to investigate the safety and tolerability of iv LCM as 
replacement for oral LCM therapy in pediatric subjects with epilepsy aged ≥4 to <17 years. A 
separate Phase 2/3 study investigating the use of iv LCM as replacement for oral LCM therapy in
pediatric subjects with epilepsy ≥1 month to <4 years of age is planned. The results of EP0060 
will provide safety and PK data regarding the use of the iv LCM formulation in pediatric subjects 
(≥4 to <17 years of age). The EP0060 design is based on the study design for SP757, which 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 94 of 240
evaluated iv LCM replacement in adults with partial-onset seizures, as well as based on design 
elements of other pediatric iv AED studies.
The iv LCM formulation is approved at doses of 200 to 400mg/day as adjunctive therapy in the 
treatment of partial-onset seizures in subjects ≥16 years of age (depending on country-specific 
labeling) with epilepsy when oral administration is temporarily not feasible. 
A weight-based LCM dosing scheme for pediatric subjects is being evaluated in Phase 3 
double-blinded, placebo-controlled studies and targets similar LCM plasma concentrations as 
those observed in adults given 400mg/day. As such, the target doses of LCM for the Phase 3 
studies are 8 to 12mg/kg/day; however, subjects entering EP0060 can be on a wider range of 
LCM doses based on the ranges of doses allowed in the long-term, open-label studies (2 to 
12mg/kg/day or 100 to 600mg/day). Thus, the iv LCM doses being evaluated in EP0060 will 
range from 2 to 12mg/kg/day or 100 to 600mg/day for subjects enrolling from the long-term 
open-label studies and for subjects currently prescribed VIMPAT and enrolling directly into 
EP0060. 
EP0060 will initially enroll older pediatric subjects (Cohort 1), which will include at least 
20 subjects ≥12 to <17 years of age. Cohort 2 (at least 20 subjects ≥8 to <12 years of age) and 
Cohort 3 (at least 20 subjects ≥4 to <8 years of age) will follow sequentially based on DMC 
recommendation. After the first 10 subjects in each cohort have received iv LCM over infusion
durations of 30 to 60 minutes, the enrollment will be temporarily put on hold for the DMC to 
review the available safety and tolerability data. Based on their review, the DMC will 
recommend the target infusion duration for the remaining subjects in the cohort (ie, 30 to 
60 minutes or 15 to 30 minutes), if the study/cohort should be stopped, and if the next cohort can 
be initiated, and if a new iv LCM study in younger pediatric subjects (≥1 month to <4 years of 
age) can be initiated.
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM in subjects ≥4 to <17 years of age over a range of infusion 
durations. Taken together, the iv LCM dosing scheme and planned target infusion durations 
being evaluated in EP0060 (2 to 12mg/kg/day or 100 to 600mg/day; 15 to 60 minutes) allow for 
administration of a range of pediatric doses, and include infusion durations that are the same as 
those approved for adults and adolescents.
Change #15
Section 6.1 Inclusion criteria
2. Subject/legal representative 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 is male or female from ≥1 month to <17 years of age. Note: For preterm infants 
<1 year old, the corrected gestational age should be used (calculated by subtracting the 
number of weeks born before 37 weeks of gestation from the chronological age).
5. Subject has, in the opinion of the investigator, adequate seizure control for participation in 
EP0060, and is able to comply with all study requirements including hospitalization, multiple 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 95 of 240
blood draws, and iv infusions. Subject (or parent[s] or legal representative) is willing to 
comply with all study requirements.
10. Subject has been prescribed oral VIMPAT at a dose of 2mg to 12mg/kg/day or 100mg to 
600mg/day. 
11. Subject has been prescribed oral VIMPAT for the treatment of epilepsy for at least 1 month 
prior to Screening and has not been prescribed or maintained on VIMPAT for the purposes of 
participating in EP0060. Prescribed oral VIMPAT dose must be stable for at least 7 days, and 
intake of the prescribed total daily dose confirmed for at least 3 days prior to participation.
12. Subject is on a stable dosage regimen of at least 1 AED. The daily dosage regimen of AED 
therapy must be kept constant for a period of at least 1 week prior to Screening. VNS is 
allowed, but settings must be kept constant for a period of at least 1 week prior to Screening.
Have been changed to:
2. Subject/legal representative is considered reliable and capable of adhering to the protocol, 
visit schedule, and medication intake according to the judgment of the investigator.
3. Subject is male or female from ≥4 to <17 years of age.
4. Subject has, in the opinion of the investigator, adequate seizure control for participation in 
EP0060, and is able to comply with all study requirements including admission to the health 
care facility, multiple blood draws, and iv infusions. Subject (or parent[s] or legal 
representative) is willing to comply with all study requirements.
10. Subject has been prescribed oral VIMPAT at a dose of 2mg/kg/day to 12mg/kg/day (for 
subjects <50kg) or 100mg/day to 600mg/day (for subjects ≥50kg). 
11. Subject has been prescribed oral VIMPAT for the treatment of epilepsy for at least 1 month 
prior to Screening and has not been prescribed or maintained on VIMPAT for the purposes of 
participating in EP0060. Prescribed oral VIMPAT dose must be stable for at least 7 days, and 
intake of the prescribed total daily dose confirmed for at least 3 days prior to first infusion.
12. If the subject is on a concomitant AED, the daily dosage regimen of AED therapy must be 
kept constant for a period of at least 1 week prior to Screening. VNS is allowed, but settings 
must be kept constant for a period of at least 1 week prior to Screening.
The following inclusion criterion has been deleted:
4. Subject must be a minimum of 4kg in body weight.
And the following inclusion criterion has been added:
5. Subject is participating in a long-term, open-label study with LCM or is currently prescribed 
oral VIMPAT and needs to undergo a procedure, is admitted to an EMU or health care 
facility, or other situations where iv administration of LCM is clinically appropriate.
Change #16
Section 6.2 Exclusion criteria
6. Subjects who do not have a diagnosis of epilepsy.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 96 of 240
9. Subject has a medical condition that could reasonably be expected to interfere with drug 
absorption, distribution, metabolism, or excretion.
12. Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total 
bilirubin level greater than or equal to 2 times the upper limit of normal (ULN), or creatinine 
clearance less than 50mL/min.
21. Subject has a known sodium channelopathy, such as Brugada syndrome.
Have been changed to:
5. Subject does not have a diagnosis of epilepsy.
8. Subject has a medical condition that could reasonably be expected to interfere with drug 
distribution, metabolism, or excretion.
11. Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total 
bilirubin level greater than or equal to 2 times the upper limit of normal (ULN), or creatinine 
clearance less than 30mL/min.
19. Subject has a known cardiac sodium channelopathy, such as Brugada syndrome.
And the following exclusion criteria have been deleted:
2. Subject, in the investigator’s opinion, would be expected to stay in the hospital or on iv LCM 
longer than 5 days.
18. Subject has been treated with vigabatrin for at least 12 months prior to entering EP0060 and 
has experienced any toxicity issues with this treatment. Note: Any subject who is currently 
treated with vigabatrin, and has received vigabatrin for a period of less than 12 months, is 
excluded from EP0060. Subjects who have received vigabatrin in the past must have 
documentation of an assessment for visual field defects after completion of vigabatrin 
therapy.
Change #17
Section 7.2 Treatment(s) to be administered
Treatment Period (up to 5 days)
During the Treatment Period, iv LCM will be administered twice daily at 12-hour intervals, once 
in the morning and once in the evening. The iv LCM dose will be equivalent (mg-for-mg) to the 
subject’s current stable oral LCM dose or prescribed oral VIMPAT dose (always in bid regimen) 
of 2 to 12mg/kg/day or 100 to 600mg/day. The first iv LCM dose will be given on Day 1.
A calibrated infusion pump should be used for delivering the iv LCM dose at a constant rate over 
the target duration defined for the cohort. A previously unused vial must be administered for 
each dose. Dilution is not required prior to administration of iv LCM. If needed to obtain a total 
volume compatible with the specified infusion duration, the iv LCM solution can be diluted; 
iv LCM is compatible with the following diluents: dextrose 5%, lactated ringers, and normal 
saline (NaCl 0.9%). The total volume of diluent should be calculated not to exceed a total 
volume of fluid intake/day of 100mL/kg body weight. Intravenous LCM administration should 
be completed within 4 hours after dilution.
For subjects enrolled into Cohort 1, iv LCM should be infused as follows:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 97 of 240
x Over a target duration of 30 minutes but no longer than 60 minutes whenever possible. 
After review of the Cohort 1 data, the DMC will make a recommendation for the target infusion 
duration to be evaluated in Cohort 2: 
x EITHER 15 minutes but no longer than 30 minutes whenever possible, 
x OR 30 minutes but no longer than 60 minutes whenever possible. 
If the 30 minutes but no longer than 60 minutes infusion duration is repeated, enrollment into the 
study will be stopped once Cohort 2 has completed. If the Cohort 2 infusion is initiated at 
15 minutes but no longer than 30 minutes duration, the DMC will make a recommendation for 
the target infusion duration to be evaluated in Cohort 3:
x EITHER 15 minutes but no longer than 30 minutes whenever possible, 
x OR 30 minutes but no longer than 60 minutes whenever possible. 
When necessary for the safety of the subject or when the investigator deems it appropriate, the 
iv LCM dose can be modified after 1 day, once the Day 1 PK samples are taken.
A subject cannot receive iv LCM for more than 5 days in EP0060. Once the subject has 
completed the Treatment Period (up to 10 infusions from Day 1 to Day 5 of iv LCM), the subject 
will need to discontinue EP0060. If a subject requires iv LCM treatment for more than 5 days, 
the subject will need to discontinue EP0060. Subjects who were enrolled in a long-term, 
open-label study may be eligible to resume participation in that study, according to the protocol 
requirements. If subjects need to discontinue LCM, the subjects should be tapered off LCM 
gradually as specified in their long-term, open-label study. This taper should occur as a part of 
the long-term, open-label study.
Subjects who were prescribed oral VIMPAT should continue AED treatment at the discretion of 
the treating physician. 
Has been changed to:
Treatment Period (up to 5 days)
During the Treatment Period, iv LCM will be administered bid at approximately 12-hour 
intervals, once in the morning and once in the evening, for up to 5 days. The iv LCM dose will 
be equivalent (mg-for-mg) to the subject’s current stable oral LCM dose or prescribed oral 
VIMPAT dose (always in bid regimen) of 2 to 12mg/kg/day or 100 to 600mg/day. The first 
iv LCM dose will be given on Day 1.
A calibrated infusion pump should be used for delivering the iv LCM dose at a constant rate over 
the target duration defined for the cohort. A previously unused vial must be administered for 
each dose. Dilution is not required prior to administration of iv LCM. If needed to obtain a total 
volume compatible with the specified infusion duration, the iv LCM solution can be diluted; 
iv LCM is compatible with the following diluents: dextrose 5%, lactated ringers, and normal 
saline (NaCl 0.9%). The total volume of diluent should be calculated not to exceed a total 
volume of fluid intake/day based on the Holliday-Segar equation as follows: 
x For children weighing ≤10kg: 100mL/kg body weight
x For children weighing >10 to ≤20kg: 1000mL + 50mL/kg for each kg body weight ≥10kg
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 98 of 240
x For children weighing ≥20kg: 1500mL + 20mL/kg for each kg body weight ≥20kg
Intravenous LCM administration should be completed within 4 hours after dilution.
For the first 10 subjects ≥12 to <17 years of age enrolled into Cohort 1, iv LCM should be 
infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. 
The duration of infusion for the remaining subjects in Cohort 1 and subsequent cohort(s) will be 
based on DMC recommendation: 
x 30 minutes but no longer than 60 minutes whenever possible,
x OR 15 minutes but no longer than 30 minutes whenever possible.
Further details on the timing on DMC recommendations regarding infusion duration are provided 
in Section 12.7.2.
When necessary for the safety of the subject or when the investigator deems it appropriate, the 
iv LCM dose can be modified after the first infusion, once the Day 1 PK samples have been 
taken. 
A subject cannot receive iv LCM for more than 5 days in EP0060. If a subject requires iv LCM 
treatment for more than 5 days, the subject may continue on iv VIMPAT, but he/she will need to 
discontinue EP0060. Subjects who were enrolled in a long-term, open-label study may be 
eligible to resume participation in that study, according to the protocol requirements. If subjects 
need to discontinue LCM, the subjects should be tapered off LCM gradually as specified in their 
long-term, open-label study. This taper should occur as a part of the long-term, open-label study.
Subjects who were prescribed oral VIMPAT should continue AED treatment at the discretion of 
the treating physician.
Change #18
Section 7.8.1 Permitted and prohibited concomitant treatments (medications and therapies)
Only stable use of amphetamines and sedative antihistamines are permitted during the study. 
Also, only stable low doses of anxiolytics or hypnotics are allowed for nonepilepsy indications.
The following concomitant medications that influence the central nervous system are prohibited 
during EP0060:
x Neuroleptics
x MAOIs
Subjects who have been treated with ethosuximide are excluded from the study. Concomitant use 
of either vigabatrin or ethosuximide during the course of the study is prohibited.
Therapy which becomes necessary in the investigator’s opinion during the course of the study 
must not be refused to a subject even if described above as therapy that is expressly not 
permitted. In such cases, the subject’s participation in EP0060 will be discontinued.
Has been changed to:
Stable use of amphetamines and sedative antihistamines is permitted during the study. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 99 of 240
Use of MAOIs is prohibited during EP0060.
Therapy which becomes necessary in the investigator’s opinion during the course of the study 
must not be refused to a subject even if described above as therapy that is expressly not 
permitted. In such cases, the subject’s participation in EP0060 may be discontinued.
Change #19
Section 7.8.2 Rescue medication
The use of oral or rectal benzodiazepines is restricted to intermittent use as rescue medication.
Has been deleted 
Change #20
Section 8 STUDY PROCEDURES BY VISIT
The following subheadings have been added:
8.1 Screening/Baseline Period
8.2 Treatment Period
8.4 End-of-Study Period
Change #21
Section 8.1
Visit 1a and Visit 1b (Day -7 to Day -1) Screening and/or Baseline
Prior to the conduct of any study related procedures, a complete explanation (both verbally and 
written) of the nature and purpose of the study will be given to the subject (when possible or as 
required according to local IRBs/IECs) and the subject’s parent/legal guardian by the 
investigator (or designee). The subject’s parent/legal guardian will be requested to sign and date 
the IRB/IEC-approved Informed Consent form. When possible, or as required by the local 
IRB/IEC, an IRB/IEC-approved written Assent form will also be properly executed and 
documented. During the Screening Period, subjects will be evaluated for their suitability for 
enrollment. The Screening Period assessments may be conducted on more than 1 day and begin 
up to 7 days prior to Day 1 (Visit 1a). Screening may also occur 1 day prior to Day 1 (Visit 1b) 
provided all test results are available and reviewed to assess inclusion and exclusion criteria prior 
to enrollment/treatment in the study. Oral LCM will be administered in accordance with each 
subject’s current stable LCM dosage regimen of 2 to 12mg/kg/day or 100 to 600mg/day. For 
subjects enrolled in a long-term open-label study, the oral LCM will be taken from the long-term 
open-label study supply. For subjects who have been prescribed VIMPAT, oral LCM will be 
taken from the subject’s prescribed VIMPAT supply.
When necessary for the well-being of the subject or when the investigator deems it appropriate, 
the hospitalization, screening laboratories, and the first iv LCM infusion can start on the same 
day provided all results are available and reviewed for inclusion/exclusion criteria prior to the 
start of infusion/treatment.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 100 of 240
Each subject’s eligibility for the study will be determined on the basis of the inclusion/exclusion 
criteria and the results of the following pretreatment assessments at Visit 1a:
x Height, weight, and body mass index (BMI)
x Medical procedures
x Procedure history
x Diagnosis of epilepsy
x Childbearing potential
x Medical history update for subjects from long-term open-label studies, or complete medical 
history for subjects receiving prescribed VIMPAT
x Lacosamide dosing history (including time and quantity during the last 3 days)
x Prior and concomitant medication(s) assessment 
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
x Pregnancy testing for subjects of childbearing potential will be serum testing at the Screening 
Visit for subjects who are prescribed VIMPAT and urine testing for subjects enrolled in 
long-term, open-label studies
x Withdrawal criteria
x Complete neurological examination
x Complete physical examination
x Blood sample for clinical chemistry and hematology 
x Vital signs (BP and pulse) assessment
x 12-lead ECG 
x AE reporting (AEs occurring since signature of Informed Consent form). Ongoing AEs from 
the long-term open-label studies will be followed, as well as recording of new AEs during 
EP0060.
x ILAE (International League against Epilepsy) seizure classification
x Admission to the unit
x Oral LCM administration
x C-SSRS (for subjects ≥6 years of age)
x Signs and symptoms of depression for subjects <6 years of age
x The following assessments will be carried out at Visit 1b if Screening and Baseline occur on 
separate days:
x Verification that the subject continues to meet the inclusion criteria
x Lacosamide dosing history (including time and quantity during the last 3 days)
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 101 of 240
x Prior and concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
x AE reporting (AEs occurring since signature of Informed Consent form)
x Blood sample for clinical chemistry and hematology 
x Withdrawal criteria
x Vital signs (BP and pulse) assessment
x 12-lead ECG
x Admission to the unit
x Oral LCM administration
x C-SSRS (for subjects ≥6 years of age)
x Signs and symptoms of depression for subjects <6 years of age
Has been changed to:
Section 8.1.1 Visit 1a and Visit 1b (Day -7 to Day -1) Screening and/or Baseline
Prior to the conduct of any study-related procedures, a complete explanation (both verbally and 
written) of the nature and purpose of the study will be given to the subject (when possible or as 
required according to local IRBs/IECs) and the subject’s parent/legal guardian by the 
investigator (or designee). The subject’s parent/legal guardian will be requested to sign and date 
the IRB/IEC-approved Informed Consent form. When possible, or as required by the local 
IRB/IEC, an IRB/IEC-approved written Assent form will also be properly executed and 
documented. During the Screening Period, subjects will be evaluated for their suitability for 
enrollment. The Screening Period assessments may be conducted on more than 1 day and begin 
up to 7 days prior to Day 1 (Visit 1a). When necessary for the well-being of the subject or when
the investigator deems it appropriate, the Screening and/or Baseline Visit can occur on the same 
day as the first iv LCM infusion (Day 1) provided all test results are available and reviewed to 
assess inclusion and exclusion criteria prior to enrollment/treatment in the study. Oral LCM will 
be administered in accordance with each subject’s current stable LCM dosage regimen of 2 to 
12mg/kg/day or 100 to 600mg/day. For subjects enrolled in a long-term open-label study, the 
oral LCM will be taken from the long-term open-label study supply. For subjects who have been 
prescribed VIMPAT, oral LCM will be taken from the subject’s prescribed VIMPAT supply.
Each subject’s eligibility for the study will be determined on the basis of the inclusion/exclusion 
criteria at Visit 1a and/or Visit 1b. The following pretreatment assessments will be carried out at 
Visit 1a:
x Height and weight 
x Medical procedures
x Procedure history
x Diagnosis of epilepsy
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 102 of 240
x Childbearing potential
x Medical history update for subjects from long-term open-label studies, or complete medical 
history for subjects receiving prescribed VIMPAT
x Lacosamide dosing history (including formulation, date, and time of use, and dose and unit 
during the last 3 days)
x Prior and concomitant medication(s) assessment (prior medications will only be collected for 
direct-enroll subjects; concomitant medications from the long-term open-label studies will be 
followed, as well as the recording of new concomitant medications during EP0060 for all 
enrolled subjects)
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
x Pregnancy testing for subjects of childbearing potential will be serum testing at the Screening 
Visit for subjects who are prescribed VIMPAT and urine testing for subjects enrolled in 
long-term, open-label studies
x Withdrawal criteria
x Complete neurological examination
x Complete physical examination
x Blood sample for clinical chemistry and hematology 
x Vital signs (BP and pulse rate) assessment
x 12-lead ECG 
x AE reporting (AEs occurring since signature of Informed Consent form). Ongoing AEs from 
the long-term open-label studies will be followed, as well as recording of new AEs during 
EP0060.
x ILAE (International League against Epilepsy) seizure classification
x Admission to the unit
x Oral LCM administration
x C-SSRS (for subjects ≥6 years of age)
x The following assessments will be carried out at Visit 1b if Screening and Baseline occur on 
separate days:
x Verification that the subject continues to meet the inclusion criteria
x Lacosamide dosing history (including formulation, date, and time of use, and dose and unit 
during the last 3 days)
x Prior and concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 103 of 240
x AE reporting (AEs occurring since signature of Informed Consent form)
x Blood sample for clinical chemistry and hematology 
x Withdrawal criteria
x Vital signs (BP and pulse rate) assessment
x 12-lead ECG
x Admission to the unit
x Oral LCM administration
x C-SSRS (for subjects ≥6 years of age)
Change #22
Section 8.2
Visit 2 (Day 1)
Intravenous LCM infusion treatment will begin at this visit and the following assessments will be 
carried out. Screening laboratory assessments may be conducted up to the day of the infusion
provided they are reviewed and meet inclusion/exclusion criteria prior to the infusion.
x Confirmation of inclusion criteria and exclusion criteria
x Intravenous LCM infusion
x Prior and concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
x Withdrawal criteria
x AE reporting
x 12-lead ECG (prior to iv LCM infusion and at 15, 30, 60 minutes, and 2 hours from the start 
of iv LCM infusion)
x Vital signs of BP and pulse rate (5 minutes prior to iv LCM infusion and at 5, 10, 20, 45, 
60 minutes, and 2 hours from the start of iv LCM infusion)
x Blood sample for LCM PK (Blood draws will be performed on the arm opposite the arm 
where the iv LCM infusion will be administered. An indwelling cannula used for the iv LCM 
infusion may not be used for PK blood sampling.) 
x C-SSRS (for subjects ≥6 years of age)
x Signs and symptoms of depression for subjects <6 years of age
x Intravenous LCM infusion and the following assessments will be carried out during the 
evening (PM) at approximately 12 hours after the start of the AM infusion:
x Intravenous LCM infusion
x Concomitant medication(s) assessment
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 104 of 240
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
x AE reporting
x 12-lead ECG (prior to iv LCM infusion and at 15, 30, 60 minutes, and 2 hours from the start 
of iv LCM infusion)
x Vital signs of blood pressure and pulse rate (5 minutes prior to iv LCM infusion and at 5, 10, 
20, 45, 60 minutes, and 2 hours from the start of iv LCM infusion)
x Withdrawal criteria
x Signs and symptoms of depression for subjects <6 years of age
Has been changed to:
Section 8.2.1 Visit 2 (Day 1)
Intravenous LCM infusion treatment will begin at this visit, and iv LCM will be administered bid 
at approximately 12-hour intervals, once in the morning and once in the evening, for up to 
5 days. Screening laboratory assessments may be conducted up to and including the day of the 
infusion provided they are reviewed and meet inclusion/exclusion criteria prior to the infusion. 
The following assessments will be carried out:
x Intravenous LCM infusion
x Medical procedures and medical history update
x Prior and concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
x Withdrawal criteria
x AE reporting
x 12-lead ECG (approximately 20 minutes prior to iv LCM infusion and at approximately 15, 
30, 60 minutes, and 2 hours from the start of iv LCM infusion)
x Vital signs of BP and pulse rate (approximately 10 minutes prior to iv LCM infusion and at 
approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of iv LCM infusion)
x Blood sample for LCM PK (Blood draws will be performed on the arm opposite the arm 
where the iv LCM infusion will be administered at the time points described in Section 9).
An indwelling cannula used for the iv LCM infusion may not be used for PK blood
sampling.) 
x C-SSRS (for subjects ≥6 years of age)
x The second iv LCM infusion will be administered at approximately 12 hours after the start of 
the first infusion, and the following assessments will be carried out:
x Intravenous LCM infusion
x AE reporting
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 105 of 240
x 12-lead ECG (approximately 20 minutes prior to iv LCM infusion and at approximately 15, 
30, 60 minutes, and 2 hours from the start of iv LCM infusion)
x Vital signs of BP and pulse rate (approximately 10 minutes prior to iv LCM infusion and at 
approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of iv LCM infusion)
x Withdrawal criteria
Change #23
Section 8.3
Visit 3 (Day 2 to Day 5)
Assessments for Visit 3 (Day 2 to 5) are the same as those described for Visit 2 (Day 1) in 
Section 8.2.
Has been changed to:
Section 8.2.2 Visit 3 (Day 2 to Day 5)
If iv LCM treatment is continued after Day 1, assessments for Visit 3 must be completed each 
day of iv LCM treatment in EP0060. Assessments for Visit 3 (Day 2 to 5) are the same as those 
described for Visit 2 (Day 1) in Section 8.2. Blood samples for LCM PK will be obtained before 
and after the final iv LCM infusion at the time points described in Section 9. In addition, during 
the course of the study, additional blood samples for PK analysis can be taken at the discretion of 
the investigator, especially in the event of a relevant treatment-emergent AE.
Change #24
Section 8.4 Unscheduled Visit
The following assessments will be carried out during the Unscheduled Visit:
x Concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose) 
and/or VNS settings
x AE reporting
x 12-lead ECG
x Blood pressure and pulse rate
x Blood sample for LCM PK (Blood draws will be performed on the arm opposite the arm 
where the iv LCM infusion will be administered. An indwelling cannula used for the iv LCM 
infusion may not be used for PK blood sampling)
x Withdrawal criteria
x C-SSRS (for subjects ≥6 years of age). The C-SSRS assessment should be completed if the 
Unscheduled Visit is due to an AE.
x Signs and symptoms of depression for subjects <6 years of age
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 106 of 240
Has been changed to: 
Section 8.3 Unscheduled Visit
The following assessments will be carried out during the Unscheduled Visit:
x Medical procedures and medical history update
x Concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose) 
and/or VNS settings
x AE reporting
x 12-lead ECG
x BP and pulse rate
x Blood sample for LCM PK (Blood draws will be performed on the arm opposite the arm 
where the iv LCM infusion will be administered. An indwelling cannula used for the iv LCM 
infusion may not be used for PK blood sampling)
x Withdrawal criteria
x C-SSRS (for subjects ≥6 years of age). The C-SSRS assessment should be completed if the 
Unscheduled Visit is due to an AE.
Change #25
Section 8.5 Final Visit (Day 2 to 6)/Termination Visit
The following assessments will be carried out the day after the last dose of iv LCM for subjects 
who complete the study, discontinue the study or withdraw from the study prematurely:
x Concomitant medication(s) assessment
x Pregnancy testing for subjects of childbearing potential 
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose) 
and/or VNS settings
x AE reporting
x Complete physical examination
x Complete neurological examination
x Blood sample for clinical chemistry and hematology
x 12-lead ECG
x Blood pressure and pulse rate
x Withdrawal criteria
x Oral LCM administration
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 107 of 240
x C-SSRS (for subjects ≥6 years of age) if the Unscheduled Visit is due to an AE
x Signs and symptoms of depression for subjects <6 years of age 
x Discharge from the unit
Has been changed to:
Section 8.4.1 Final Visit (Day 2 to 6)/Termination Visit
The following assessments will be carried out the day after the last dose of iv LCM for subjects 
who complete the study, discontinue the study, or withdraw from the study prematurely:
x Medical procedures and medical history update
x Concomitant medication(s) assessment
x Pregnancy testing for subjects of childbearing potential 
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose) 
and/or VNS settings
x AE reporting
x Complete physical examination
x Complete neurological examination
x Blood sample for clinical chemistry and hematology
x 12-lead ECG
x BP and pulse rate
x Withdrawal criteria
x Oral LCM administration
x C-SSRS (for subjects ≥6 years of age) 
x Discharge from the unit
Change #26
Section 8.6
Follow-Up Period (Day 2 to Day 9)
One or 2 days after the last dose of iv LCM in the Treatment Period, a safety 
follow-up/telephone assessment will be conducted during the Follow-Up Period (2 to 9 days 
after Visit 2/Day 1). The following assessments will be collected:
Concomitant medication(s) assessment
AE reporting
Oral LCM administration
During the contact, the site should inquire as to whether the subject noted any change at the site 
of the infusion.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 108 of 240
Has been changed to:
Section 8.4.2 Telephone Contact (Day 2 to Day 9)
One or 2 days after the Final Visit, a safety follow-up/telephone assessment will be conducted 
during the End-of-Study Period (2 to 9 days after Visit 2/Day 1). The following assessments will 
be collected:
x Medical procedures and medical history update
x Concomitant medication(s) assessment
x AE reporting
x Oral LCM administration
During the contact, the site should inquire as to whether the subject noted any change at the site 
of the infusion.
Change #27
Section 9 ASSESSMENT OF PHARMACOKINETICS
Blood samples for the determination of LCM and SPM12809 concentrations will be collected 
according to the tabular schedules of study procedures (see Section 5.2). In each case, the time 
the subject received the most recent dose of study medication and the time of blood sampling 
must be recorded.
During the Treatment Period, plasma samples will be taken for LCM determination after ECG 
and vital signs have been taken from the opposite arm in which the solution for infusion was 
administered on Day 1 and Day 5/Early Termination at the following time points: 
x Predose (within 1 hour prior to iv LCM dose)
x Post dose (within 1 to 4 hours after end of iv LCM infusion)
x Final Treatment Visit (within 1 hour prior to the first iv LCM dose and 1 to 4 hours after the 
second iv LCM dose)
The study-related blood loss (including any losses in the maneuver), per study subject, will not 
exceed 3% of the total blood volume during a period of 4 weeks and will not exceed 1% at any 
single time. The total volume of blood is estimated at 80 to 90mL/kg body weight; 3% is 2.4mL 
of blood per kg of body weight. With today’s microanalytical techniques, plasma samples for 
drug level determinations can be small, with less than 1mL needed.
Details of plasma sample collection and processing, sample labeling, and shipment will be 
provided in the laboratory manual. 
Has been changed to:
Blood samples for the determination of LCM and SPM 12809 concentrations will be collected 
according to the tabular schedules of study procedures (see Section 5.2). In each case, the time 
the subject received the most recent dose of study medication and the time of blood sampling 
must be recorded.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 109 of 240
During the Treatment Period, plasma samples will be taken for LCM and SPM 12809
determination after ECG and vital signs have been taken. Plasma samples will be obtained from 
the opposite arm in which the solution for infusion was administered, at the following time 
points:
First iv LCM infusion (Day 1):
x Predose (within 1 hour prior to iv LCM dose)
x Postdose (within 1 to 4 hours after end of iv LCM infusion)
x Final iv LCM infusion (Day 2 to 5/Early Termination):
x Predose (within 1 hour prior to iv LCM dose)
x Postdose (within 1 to 4 hours after end of iv LCM infusion)
Additional blood samples for PK analysis can be taken at the discretion of the investigator, 
especially in the event of a relevant treatment-emergent AE.
The study-related blood loss (including any losses in the maneuver), per study subject, will not 
exceed 3% of the total blood volume during a period of 4 weeks and will not exceed 1% at any 
single time. The total volume of blood is estimated at 80 to 90mL/kg body weight; 3% is 2.4mL 
of blood per kg of body weight. With today’s microanalytical techniques, plasma samples for 
drug level determinations can be small, with less than 1mL needed.
Details of plasma sample collection and processing, sample labeling, and shipment will be 
provided in the laboratory manual.
Change #28
Section 10.1.1.1 Signs and symptoms of depression
Subjects should be monitored for any changes in mood, ideas, or behavior for warning signs of 
depression. The investigator should be aware of common warning signs that might be a signal for 
risk of depression. For common signs and symptoms of depression in children, reference should 
be made to the current version of the Diagnostic and Statistical Manual of Mental Disorders. 
Each subject’s parent(s)/legal representative(s)/caregiver(s) (in accordance with local regulation) 
should also be advised accordingly and effort should be made at clinic visits to specifically 
assess potential depression.
Section has been deleted
Change #29
Section 10.1.6 Pregnancy, bullets 
x The subject should be withdrawn from the study.
x The subject should immediately stop the intake of iv LCM or be down-titrated as instructed 
at the early discontinuation visit. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 110 of 240
x A Safety Follow-Up Visit should be scheduled 1 to 2 days after the subject has discontinued 
her iv LCM infusion.
Have been changed to:
x The subject may need to discontinue iv LCM. The decision to stop the intake of iv LCM will 
be at the discretion of the investigator. 
x A Safety Follow-Up Visit should be scheduled 1 to 2 days after the subject has discontinued 
her iv LCM infusion.
Change #30
Section 10.7.1 Vital signs, body weight, height and BMI 
Noninvasive measurements of BP (systolic and diastolic) and pulse rate will be performed at 
clinic visits in a sitting position after at least 3 minutes at rest, when feasible, according to the 
tabular schedule of study assessments (Section 5.2). Body weight will be determined without 
shoes and wearing light clothing, and height will be measured without shoes; body weight and 
height, will be assessed according to the tabular schedule of study procedures (Section 5.2).
Has been changed to:
Section 10.7.1 Vital signs, body weight, and height
Noninvasive measurements of BP (systolic and diastolic) and pulse rate will be performed after 
at least 3 minutes at rest, when feasible, according to the tabular schedule of study assessments 
(Section 5.2). Body weight will be determined without shoes and wearing light clothing, and 
height will be measured without shoes; body weight and height will be assessed according to the 
tabular schedule of study procedures (Section 5.2).
Change #31
Section 10.7.2 12-lead ECG, paragraph 2
Care should be taken to assure proper lead placement and quality ECG recordings. Subjects 
should rest in a supine position at least 5 minutes prior to each recording and should be 
motionless during the recording, when feasible.
Has been changed to:
Care should be taken to assure proper lead placement and quality ECG recordings. Subjects 
should rest at least 5 minutes prior to each recording and should be motionless during the 
recording, when feasible.
Change #32
Section 10.7.5 Assessment of suicidality
Suicidality will be assessed by trained study personnel using the C-SSRS (Columbia University 
Medical Center, 2008). For subjects ≥6 years of age, this scale will be used for screening as well 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 111 of 240
as to assess suicidal ideation and behavior that may occur during the study. The C-SSRS will be 
completed according to the tabular schedule of study procedures (Table 5-1). 
The C-SSRS is not validated and will not be used for subjects <6 years of age. Signs and 
symptoms of depression for subjects <6 years of age will also be assessed whenever a C-SSRS 
assessment is performed. Subjects should be monitored for any changes in mood, ideas, or 
behavior for warning signs of depression. The investigator should be aware of common warning 
signs that might be a signal for risk of depression. For common signs and symptoms of 
depression in children younger than 6 years old, reference should be made to the current version 
of the Diagnostic and Statistical Manual of Mental Disorders. Parents and caregivers should also 
be advised accordingly and effort should be made at clinic visits to specifically assess potential 
depression.
Has been changed to:
Suicidality will be assessed by trained study personnel using the C-SSRS (Columbia University 
Medical Center, 2008). For subjects ≥6 years of age, this scale will be used for screening as well 
as to assess suicidal ideation and behavior that may occur during the study. The C-SSRS will be 
completed according to the tabular schedule of study procedures (Table 5-1). All subjects who 
are ≥6 years of age will complete the “Baseline/Screening” version of the C-SSRS at Visit 1 and 
will complete the “Since Last Visit” version at subsequent visits. If a subject becomes 6 years of 
age during the study, the "Already Enrolled" version of the C-SSRS should be used at the first 
visit at which the subject is 6 years of age and the “Since Last Visit” version used at subsequent 
visits.
The C-SSRS is not validated for subjects <6 years of age and will not be used for this population. 
Subjects should be monitored for any changes in mood, ideas, or behavior for warning signs of 
depression. The investigator should be aware of common warning signs that might be a signal for 
risk of depression. For common signs and symptoms of depression in children younger than 
6 years old, reference should be made to the current version of the Diagnostic and Statistical 
Manual of Mental Disorders. Parents and caregivers should also be advised accordingly and 
effort should be made at clinic visits to specifically assess potential depression.
Change #33
Section 12 STATISTICS
Selected disposition, exposure, demographic, and Baseline summaries will be presented by 
cohort and all subjects overall. Descriptive statistics will be displayed to provide an overview of 
the Baseline characteristics, pharmacokinetic, and safety results. For categorical variables, these 
will consist of the number and percentage of subjects in each category. The denominator and 
percentage will be based on the number of subjects appropriate for the purpose of analysis. For 
continuous variables, display of descriptive statistics will generally include n (number of 
subjects), mean, standard deviation (SD), median, minimum, and maximum.
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan.
Has been changed to:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 112 of 240
Selected disposition, exposure, demographic, and Baseline summaries will be presented by 
cohort and infusion duration, cohorts overall, and all subjects overall. Descriptive statistics will 
be displayed to provide an overview of the Baseline characteristics, PK, and safety results.
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan.
Change #34
Section 12.3 Planned pharmacokinetic analyses
Descriptive statistics for LCM plasma concentrations, including but not limited to geometric 
mean and coefficient of variation (CV%), will be computed for pre-infusion and post-infusion
time points on each infusion day where LCM plasma is collected.
If an adequate number of samples are collected on Day 5, then statistical comparisons between 
trough plasma concentrations from Day 1 and Day 5 as well as post-infusion plasma 
concentrations from Day 1 and Day 5 will be performed.
Has been changed to:
Descriptive statistics for LCM and SPM 12809 plasma concentrations, including but not limited 
to geometric mean and CV, will be computed for pre-infusion and post-infusion time points on 
each infusion day where LCM and SPM 12809 plasma are collected.
Change #35
Section 12.5
Handling of protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct, or on the primary efficacy, key safety, or PK/PD outcomes 
(if applicable) for an individual subject. The criteria for identifying important protocol deviations 
will be defined within the appropriate protocol-specific document. Important protocol deviations 
will be reviewed as part of the ongoing data cleaning process and data evaluation. All important 
deviations will be identified and documented prior to database lock to confirm exclusion from 
analysis sets.
Has been changed to:
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct, or on the primary safety outcomes (if applicable) for an 
individual subject. The criteria for identifying important protocol deviations will be defined 
within the appropriate protocol-specific document. Important protocol deviations will be 
reviewed as part of the ongoing data cleaning process and data evaluation. All important 
deviations will be identified and documented prior to database lock to confirm exclusion from 
analysis sets.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 113 of 240
Change #36
Section 12.7
Planned interim analysis and data monitoring
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of each cohort.
Has been changed to:
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of the first 10 subjects in each cohort. 
Change #37
Section 12.7.1Definition of stopping rules
No formal stopping rule will be applied. The DMC may give a recommendation to stop the study 
after reviewing the safety data for Cohort 1 or Cohort 2. A recommendation for stopping should 
be based on the collective experience of the DMC members. After meeting to review data from 
each cohort, the DMC will provide a recommendation in writing, regarding whether to continue 
or to stop the study. UCB will consider this recommendation and ensure the study investigators 
are informed of the sponsor’s decision on how to continue as described below.
Has been changed to:
No formal stopping rule will be applied. The DMC may give a recommendation to stop the study 
after reviewing the safety data as described in 12.7.2. A recommendation for stopping should be 
based on the collective experience of the DMC members. After meeting to review data from each 
cohort, the DMC will provide a recommendation in writing regarding whether to continue or to 
stop the study. UCB will consider this recommendation and ensure the study investigators are 
informed of the sponsor’s decision on how to continue as described below.
Change #38
Section 12.7.2 Data Monitoring Committee
The DMC members will be defined in the DMC charter. After completion of Cohort 1, 
enrollment into EP0060 will be temporarily put on hold to allow for a DMC review of the safety 
and tolerability data from Cohort 1. Based on the review of the Cohort 1 data, the DMC will 
make a recommendation for the target infusion duration to be evaluated in Cohort 2. 
The DMC will reconvene after the completion of Cohort 2. If the Cohort 2 target infusion 
duration was 30 minutes but no longer than 60 minutes, enrollment into the study will be stopped 
once Cohort 2 has completed. If the Cohort 2 target infusion duration was 15 minutes but no 
longer than 30 minutes, the DMC will make a recommendation for the target infusion duration to 
be evaluated in Cohort 3. After completion of Cohort 3, the DMC will reconvene to review the 
final data to provide their overall impression.
Has been changed to:
The DMC members will be defined in the DMC charter. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 114 of 240
EP0060 will begin with Cohort 1, where at least 20 subjects ≥12 to <17 years of age will be 
enrolled to receive iv LCM. For the first 10 subjects in Cohort 1, iv LCM should be infused over 
a duration of 30 minutes but no longer than 60 minutes whenever possible. 
After completion of the first 10 subjects in Cohort 1, enrollment into Cohort 1 will be 
temporarily put on hold to allow for the DMC review of the safety and tolerability data from 
these subjects. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥8 to <12 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, enrollment into Cohort 2 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1 and Cohort 2. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 2 should be stopped, 
x AND whether Cohort 3 can be initiated.
For Cohort 3, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 3, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 3, enrollment into Cohort 3 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1, Cohort 2, and Cohort 3. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 3 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 3 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 3 should be stopped, 
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 115 of 240
Change #39
Section 12.8
Determination of sample size
No formal sample size calculation has been performed. The sample size was deemed clinically 
appropriate for the evaluation of safety, tolerability, and PK of iv LCM administration in 
pediatric subjects with epilepsy.
Has been changed to:
Approximately 75 subjects will be enrolled, which includes up to 3 cohorts of at least 
20 subjects. No formal sample size calculation has been performed. The sample size was deemed 
clinically appropriate for the evaluation of safety, tolerability, and PK of iv LCM administration 
in pediatric subjects with epilepsy.
Change #40
Section 17SPONSOR 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.
Clinical Project Manager
_____________________________
Date/Signature
Clinical Trial Biostatistician
 MPH
_____________________________
Date/Signature
Study Physician
, MD
_____________________________
Date/Signature
Clinical Program Director
_____________________________
Date/Signature
Has been changed to (and became Section 18):
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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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 116 of 240
16.2
Protocol Amendment 2
Rationale for the amendment
The primary purpose of this substantial amendment is to maximize the patient pool used in the 
evaluation of the safety of iv LCM in pediatric subjects. Thus, enrollment has been opened to 
include OLL and RxL subjects who are on a stable dose of oral LCM and elect to receive iv 
LCM as well as IIL subjects who are not currently taking LCM and initiate adjunctive LCM 
treatment using iv LCM. This amendment has also included the option for RxL and IIL subjects 
to continue oral LCM treatment in SP848, if clinically appropriate, after completion of iv LCM 
in EP0060. Given this option for RxL and IIL subjects, 2 visits were added to the study design. If 
required, a Transition Visit has been add for RxL and IIL subjects transitioning to SP848 and 
requiring up to 7 days for scheduling of additional assessments to be performed during EP0060. 
If not transitioning to SP848, an additional telephone contact visit has been added approximately 
30 days after last infusion to collect final safety data. 
In order to provide treatment continuity, a short-term oral LCM solution may be dispensed to 
RxL and IIL subjects eligible for SP848 enrollment in the event that additional time is needed to 
schedule the Transition Visit.
Enrollment from EP0012 has been removed as has enrollment from future pediatric studies.
The study design was changed to merge the previous Cohort 1 (≥12 to <17 years of age) and 
Cohort 2 (≥8 to <12 years of age) into 1 cohort spanning the age range of ≥8 to <17 years of age 
while maintaining the combined planned enrollment for this age group. The decision to combine 
these 2 age groups is supported by the following 3 considerations: PK modeling, growth chart 
information, postmarketing safety assessment of iv LCM use, and a recent publication (Arkilo, et 
al 2016). 
x In the oral and iv LCM PK pediatric modeling CL0266, simulations of iv LCM infused 
over durations of 15 to 60 minutes suggest that exposure is similar to oral administration. 
These results are consistent with the LCM PK profile and bioequivalence of iv and oral 
LCM established in adults. Thus, using the weight-based dosing adaptations for LCM 
adjunctive therapy, it is predicted that the LCM concentration at steady-state in pediatric 
subjects with partial-onset seizures will be similar to that in adults for both oral and iv 
LCM. Based on the PK modeling, the use of iv LCM is expected to be 
 in the 
pediatric patient population down to 4 years of age. 
x Based on the Centers for Disease Control and Prevention (CDC) growth charts for 
weight-for-age percentiles (2 years to 20 years of age), the ages at which a child reaches 
the 50th percentile at a weight of 50kg are 13.82 years for boys and 14.21 years for girls 
(http://www.cdc.gov/growthcharts, 2000). Therefore, average pediatric patients weighing 
50kg are approximately 2 to 3 years younger than the currently approved lower limit for 
age for VIMPAT (16 years [EU] or 17 years [US]). Based on PK modeling, LCM 
exposure in pediatric subjects weighing 50kg or more is predicted to be the same as 
exposure observed in adults.
x Postmarketing data were evaluated for the period from 01 Aug 2008 to 30 Nov 2015, and 
49 cases were identified for iv LCM formulation use in the pediatric population (in 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 117 of 240
patients 4 to <16 years of age). Based on review of these cases, no new safety concerns 
were identified. 
x Arkilo and colleagues examined use of iv LCM in 47 infants and children from 4 months 
to <12 years of age, and this study included use in nonapproved indications (ie, status 
epilepticus) (Arkilo, et al 2016). Evaluation of adverse effects was not possible for the 
11 subjects in status epilepticus. Five of remaining 36 subjects experienced sedation, and 
no new safety concerns were noted in this evaluation. 
Taken together, along with our knowledge of the safety of oral LCM in children down to 4 years 
of age, enrollment of children ≥8 to <17 years of age within the same cohort should not present a 
significant safety risk and should allow earlier benefit of access to the iv LCM option of 
treatment for those subjects who are ≥8 to <12 years of age. Initiation of the assessment of safety 
in patients ≥4 to <8 year olds will remain dependent on review of safety data from Cohort 1 by 
the DMC.
To accommodate these changes, revisions have been made to the inclusion/exclusion criteria, 
schedule of assessments, LCM dosing, and statistical analyses. 
Additional changes have been implemented for consistency with other protocols in the LCM 
pediatric program and updated language in protocol template regarding monitoring for potential 
drug-induced liver injury events.
Furthermore, administrative changes including the update of the study team have been made.
At the time of approval of this amendment, no subjects were enrolled in EP0060.
Modifications and changes
Global changes
The following changes were made throughout the protocol:
x Define the 3 subject populations that are eligible for enrollment into EP0060:
 Open-label LCM (OLL) subjects: currently receiving oral LCM as adjunctive or 
monotherapy as participants in an open-label long-term study (SP848, EP0034, or 
other pediatric study).
 Prescribed-LCM (RxL) subjects: currently receiving prescribed oral LCM from 
commercial supply (eg, VIMPAT) as adjunctive or monotherapy.
 Initiating iv LCM (IIL) subjects: not currently receiving LCM and will receive iv
LCM as adjunctive treatment in EP0060. Initiation of LCM monotherapy is not 
permitted in IIL subjects.
x Revise the subject population who will receive iv LCM as follows:
 Replacement for oral LCM treatment (OLL and RxL subjects): 
◦ 
Clinical need administration: Subjects currently taking prescribed oral LCM (or 
any enteric LCM administration, eg, LCM administration by feeding tube) who 
need to undergo a procedure and are treated at an EMU or health care facility, or 
other situations where iv administration is clinically appropriate and oral 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 118 of 240
administration is not feasible (ie, surgery). In these subjects, the maximum 
number of iv doses of LCM is 10. 
◦ 
Elective administration: Subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) and elect to receive iv 
LCM administration at an EMU or healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
 Adjunctive iv LCM treatment initiation (IIL subjects):
◦ 
Clinical need administration: Subjects not currently taking LCM who need to 
undergo a procedure, be treated at an EMU or health care facility, or other 
situations where iv administration is clinically appropriate and oral administration 
is not feasible (ie, surgery). In these subjects, the maximum number of iv doses of 
LCM is 10.
◦ 
Elective administration: Subjects not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
x Enrollment from EP0012 has been removed.
x New published data regarding use of iv LCM in children was added to the Introduction.
x As a result of extending the eligible subject population to subjects initiating treatment, the 
primary study objective was modified as follows to remove stable oral LCM dose:
 The primary objective of this study is to evaluate the safety and tolerability of iv 
LCM infusion(s) in pediatric subjects ≥4 to <17 years with epilepsy.
x Safety variables were clarified as either primary or other variables.
x Text was added to clarify that IIL subjects will not receive oral LCM during the 
Screening/Baseline Period.
x The design of the study was changed such that the Screening, Baseline, Treatment Period, 
and Final Visit may occur in 1 day, provided the subject only requires 1 iv infusion, 
results of examinations (ie, ECG, laboratory measurements) are available to allow 
verification of subject eligibility prior to infusion, and time permits for completion of 
Final Visit assessments.
x The age-staggered approach to enrollment has been modified from 3 cohorts to 2 cohorts 
while maintaining the overall number of planned subjects, which also modified the 
timing of the DMC reviews as follows:
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 119 of 240
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the Investigator, Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
Investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes. 
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the Investigator, Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
Investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes. 
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes.
x OR Cohort 2 should be stopped, 
x AND whether to initiate the assessment of safety in younger pediatric subjects (≥1 month to 
<4 years of age).
x Modifications for the number and dose of iv LCM treatment(s) were incorporated as follows:
 The number of required infusions was reduced from 2 to 1.
 Text was added to clarify the starting iv LCM dose to be administered to subjects 
initiating adjunctive LCM therapy.
x Include the option for RxL and IIL subjects to continue oral LCM treatment after completion 
of iv LCM; if determined clinically appropriate; these subjects will be given the option to 
continue oral LCM treatment in SP848.
 Inclusion of this option added a Transition Visit for arrangement of SP848 entry 
assessments.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 120 of 240
 Oral LCM solution will be dispensed only to those RxL and IIL subjects who are 
interested and eligible to enroll in SP848 in the event the additional time is required for 
arrangement of the Transition Visit.
x The options for RxL and IIL subjects to continue LCM treatment in SP848 resulted in 
changing the study periods as follows:
 For all subjects:
◦ 
Screening and/or Baseline Period (up to 7 days),
◦ 
Treatment Period 
(1) Clinical need administration: up to 10 doses or up to 5 days
(2) Elective administration: up to 2 consecutive doses over approximately 24 hours
◦ 
End-of-Study/Final Visit (1 day), 
◦ 
End-of-Study/Telephone Contact 1 (1 to 3 days),
 
Additional visits or contacts as follows:
◦ 
RxL and IIL subjects who are eligible and choose to continue oral LCM treatment for 
up to 2 years in SP848
-Transition Visit which can be concurrent with Final Visit or separate (up to 
7 days after Final Visit)
◦ 
- RxL and IIL subjects who do not continue LCM treatment in SP848
-End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM).
x Modifications to maximum study duration were incorporated as follows:
x Approximately 16 days:
 Subjects in the OLL group will resume participation in their respective study and 
either resume oral LCM treatment or follow taper regimen as described in the long-
term, open-label study accordingly.
x Approximately 23 days
 Subjects in the RxL or IIL groups who, if determined clinically appropriate, are given 
the option to continue oral LCM treatment in SP848.
x Approximately 45 days:
 Subjects in the RxL or IIL groups who will not continue oral LCM treatment in 
SP848.  
x Anticipated regions for the study were updated to North America and Europe with possibility 
for expansion into other regions.
x The following changes and clarifications were made to planned assessments:
 All pregnancy tests will be conducted on urine samples.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 121 of 240
 Medical history or medical history update will only occur at Screening/Baseline.
 Information regarding ILAE classification will no longer be collected.
 LCM dosing information since the Treatment Period will be collected at TC1, Transistion 
Visit (if applicable), and TC2 (if applicable).
 Information will be collected regarding use of ketogenic diet.
 The PK samples (predose [OLL and RxL] and postdose [all subjects]) remained required 
for the first LCM infusion. Collection of PK samples (both predose and postdose for all 
subjects) from an additional iv LCM dose was changed to optional.
 If an Unscheduled Visit is due to an AE, the C-SSRS should be performed and collection 
of a PK blood sample is at the discretion of the investigator.
 Admission and discharge from unit were removed as hospitalization is not required for 
treatment.
 Seizure history was added at Screening for RxL and IIL subjects.
 Brief physical and brief neurological examinations were added during the Treatment
Period.
 Clarification was added that brief physical examination, brief neurological examination, 
hematology/chemistry laboratory assessments, and C-SSRS should only be collected 
once per day during the Treatment Period. 
 Text was added to clarify that the C-SSRS assessment should be performed once if the 
Screening and Baseline visits occur on the same day. If the Screening/Baseline and first 
infusion occur on the same day, the C-SSRS should be performed twice (predose and 
postdose).
 A Transition Visit was added to occur within 7 days of the Final Visit for RxL and IIL 
subjects who are eligible and choose to continue LCM treatment in SP848
◦ 
The Final Visit and Transition Visit can occur on the same day.
◦ 
Transition Visit in EP0060 and Visit 1 of SP848 should occur on the same day.
 Dispensing and collection of oral LCM solution was added for RxL and IIL subjects who 
are eligible and elect to continue oral LCM treatment in SP848. 
 An additional telephone contact was added 30 days after last dose for RxL and IIL
subjects who do not continue oral LCM treatment in SP848.
 Text was added to allow use of a local laboratory except for Final Visit. Central 
laboratory must be used for Final Visit.
 Text was added to permit the use of local laboratory results obtained for routine 
diagnostic and medical care whenever possible if collected no more than 24 hours prior to 
Screening/Baseline Visit in order to minimize blood loss associated with the study.
 Text was added to clarify the approach for LCM taper for RxL and IIL subjects.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 122 of 240
 Time windows were added for collection of ECG and vital signs during the 2 hours after 
the start of infusion.
 Corrections were made in table to align with assessments listed in Section 8 of protocol.
x The inclusion and exclusion criteria were modified as follows:
 Inclusion Criteria were reordered for a more logical flow. 
 An Inclusion Criterion was added (#4 in Amendment 2) which describes the study 
population to be enrolled, ie, OLL, RxL and IIL subjects. 
 Inclusion Criterion #4 (Amendment 1) has been amended such that adequate seizure 
control is no longer required as enrollment can now include subjects initiating adjunctive 
LCM treatment. The remainder of the previous criterion is now included in Amendment 2 
Inclusion Criteria 6 and 7. 
 Inclusion Criterion #5 (Amendment 1) has been removed as enrollment can now include 
subjects initiating adjunctive LCM treatment.
 Inclusion Criteria # 7 and #8 have been combined with Inclusion Criteria #10 and #11. In 
Amendment 2, these are contained within Inclusion Criterion 5. 
 Inclusion Criterion #9 (Amendment 1) has been deleted as only 1 dose is required. 
 Inclusion Criteria #10 and #11 (Amendment 1) have been reworded to incorporate and 
update the wording regarding stability of LCM dose from Inclusion Criterion #11 into 
Inclusion Criterion #10. These criteria were then folded into Inclusion Criterion 5 in 
Amendment 2. 
 Inclusion Criterion #12 (Amendment 1) has been deleted to remove requirements of 
concomitant AEDs.
 Inclusion Criteria #5 (Amendment 2) includes requirements for subjects initiating 
adjunctive LCM treatment, including stable dose of other AEDs and permitted types of 
epilepsy.
 Exclusion Criterion #3 has been revised to clarify investigator’s assessment of 
hypotension and bradycardia.
 Exclusion Criteria #5 and #16 (Amendment 1) have been deleted as epilepsy diagnosis is 
addressed within inclusion criteria.
 Exclusion Criterion #6 (now Exclusion Criterion 5 in Amendment 2) has been reworded 
to clarify that subjects taking monoamine oxidase A inhibitors are excluded.
 Exclusion Criterion #8 (now Exclusion Criterion 7 in Amendment 2) has been revised to 
include medical condition impacting absorption since short-term oral LCM will be 
provided to eligible subjects entering SP848.
 Exclusion Criterion #11 was removed and replaced by Exclusion Criterion #20. This 
criterion updates LFT exclusion criteria in line with current UCB standards. 
 Exclusion Criterion #17 (Amendment 1) has been deleted as felbamate is permitted in the 
long-term open-label studies for OLL subjects who may enroll in EP0060. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 123 of 240
 Exclusion Criterion #17 has been added since LCM has not been evaluated in the 
treatment of status epilepticus.
 Exclusion Criterion #18 has been added to clarify that subjects with only Type IIA1 or 
Type IIA2 should not be enrolled.
 Exclusion Criterion #19 was added to clarify that subjects with Dravet’s syndrome are 
excluded from this study.
 Exclusion Criterion #21 has been added to clarify that subjects enrolling to initiate 
adjunctive LCM treatment should not have received LCM during the past 3 months.
x Withdrawal criteria were modified in the following 4 ways:
 Clarification was added that treatment should not go beyond 10 doses.
 A withdrawal criterion was added such that any subject who initiated adjunctive LCM 
treatment and required a dose adjustment during the study should be withdrawn.
 Addition language was added to incorporate Sponsor language surrounding LFT results 
and monitoring for PDILI events.
 Clarification was added about the ability of subjects requiring more than 10 iv doses 
return to or enroll in the long-term open-label study pending discussion with and 
agreement from the Medical Monitor.
x Language regarding IMP labeling, handling and storage requirements, and drug 
accountability was updated to reflect new standard Sponsor text.
x Description of the short-term oral LCM supply was added, including under what 
circumstances it would be dispensed to RxL and IIL subjects.
x Language was added regarding oral dosing of LCM for RxL and IIL subjects who require 
short-term oral LCM supply in order to arrange for SP848 enrollment.
x Prohibited medications were updated to include cannibidiols not approved or indicated for 
epilepsy by local health authorities.
x Numbering of subjects was clarified for RxL and IIL subjects.
x Text was added to clarify reporting requirements for any suspected transmission of an 
infectious agent via a medicinal product to align with updated standard Sponsor text across 
programs.
x Potential Hy’s law was added as an AE of special interest to align with updated standard 
Sponsor text across programs.
x New Sponsor text was added surrounding LFT monitoring to provide further detail regarding 
the evaluation, investigations, and follow up of PDILI events. This text is to align with FDA 
guidance for PDILI monitoring; addition of this language was not initiated on the basis of 
any new hepatic safety signal for LCM.
x A new analysis set was added to include all subjects who receive LCM (oral or iv).
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 124 of 240
x The planned PK and safety analyses were updated to include evaluation based on whether 
subject was receiving replacement treatment (OLL and RxL subjects) or initiating treatment 
(IIL subjects).
x The use of the term “admitted” has been replaced with “treated” to accurately reflect that 
treatment can occur at an EMU or healthcare facility and admission to a hospital is not 
required.
x Other changes made in this amendment are to provide clarification, are administrative in 
nature, or are to correct errors.
Specific changes
Change #1
Title page
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY AND 
TOLERABILITY OF INTRAVENOUS LACOSAMIDE AS REPLACEMENT FOR ORAL 
LACOSAMIDE IN CHILDREN (≥4 TO <17 YEARS OF AGE) WITH EPILEPSY
Has been changed to:
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY AND 
TOLERABILITY OF INTRAVENOUS LACOSAMIDE IN CHILDREN (≥4 TO <17 YEARS 
OF AGE) WITH EPILEPSY
Change #2
STUDY CONTACT INFORMATION 
Sponsor Study Physician
Name:
 MD
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Has been changed to:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 125 of 240
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Change #3
STUDY CONTACT INFORMATION 
Clinical Project Manager
Name:
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Has been changed to:
Clinical Project Manager
Name:
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 126 of 240
Change #4
STUDY CONTACT INFORMATION 
Clinical Trial Biostatistician
Name:
 MPH 
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Has been changed to:
Clinical Trial Biostatistician
Name:
MPH 
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Change #5
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA: +1 800 880 6949
Canada: +1 877 582 8842
Email
Global: DS_ICT@ucb.com (for interventional clinical studies)
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 127 of 240
Has been changed to:
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA and Canada: +1 800 880 6949 or +1 866 890 3175
Email
Global: DS_ICT@ucb.com (for interventional clinical studies)
Change #6
LIST OF ABBREVIATIONS
ICH has been revised; DS, ILAE, and RDC have been deleted; and EDC, IIL, OLL, PDILI, PS, 
and RxL were added.
Change #7
Section 1 SUMMARY
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of 
intravenous (iv) lacosamide (LCM) infusions as replacement for oral LCM in pediatric subjects 
≥4 to <17 years of age with epilepsy. A separate Phase 2/3 study investigating the use of iv LCM
as replacement for oral LCM therapy in pediatric subjects with epilepsy ≥1 month to <4 years of 
age is planned. EP0060 will include subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) who need to undergo a procedure, be 
admitted to an epilepsy monitoring unit (EMU) or health care facility, or other situations where 
iv administration is clinically appropriate. Approximately 75 subjects, who are participating in a 
long-term, open-label study with LCM (SP848, EP0034, EP0012, or other future study) or who 
are currently prescribed VIMPAT® (LCM) will be enrolled. Pediatric subjects entering into 
EP0060 from a long-term, open-label study will temporarily suspend their participation in that 
study to receive iv LCM treatment in EP0060. Subjects who enroll directly into EP0060 will 
temporarily switch from their prescribed VIMPAT oral treatment to the iv LCM formulation. 
Subjects will be enrolled from approximately 40 sites in North America, Europe, Asia Pacific, 
and Latin America. Additional sites or regions may be added if deemed necessary.
The primary objective of EP0060 is to evaluate the safety and tolerability of iv LCM infusion(s) 
in pediatric subjects ≥4 to <17 years with epilepsy, after temporarily switching from the 
equivalent stable oral LCM dose. EP0060 is planned to include up to 3 age-based cohorts of at 
least 20 subjects per cohort: ≥12 to <17 years (Cohort 1), ≥8 to <12 years (Cohort 2), and ≥4 to 
<8 years (Cohort 3). A Data Monitoring Committee (DMC) will review the safety and 
tolerability data for each cohort to make recommendations for the progression of subsequent 
cohort enrollment and iv infusion durations to be evaluated. 
EP0060 is comprised of the following study periods: 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 128 of 240
x Treatment Period (up to 5 days),
x End-of-Study/Final Visit (1 day), 
x End-of-Study/Telephone Contact (1 to 2 days). 
During the Screening Period (Day -7 to Day -1), oral LCM will be administered in accordance 
with each subject’s oral LCM dosage regimen. During the Treatment Period, subjects will 
receive iv LCM infusions twice daily (bid) at approximately 12-hour intervals for up to 5 days. 
The daily dose of iv LCM will be the same as the subject's current stable daily dose of oral LCM 
(2 to 12mg/kg/day or 100 to 600mg/day). During the Treatment Period, blood samples will be 
obtained for pharmacokinetic (PK) analysis, and detailed safety assessments will be performed. 
An End-of-Study/Final Visit will be conducted the day after the last dose of iv LCM after 
completion of or withdrawal from the Treatment Period. A safety follow-up Telephone Contact 
should occur 1 to 2 days after the End-of-Study/Final Visit. 
The maximum study duration for an individual subject will be approximately 15 days. After 
completion of or discontinuation from EP0060, only subjects who enrolled into EP0060 from a 
long-term, open-label study will resume their participation in that study and resume oral LCM 
treatment accordingly. Subjects who were prescribed VIMPAT should continue antiepileptic 
drug (AED) treatment at the discretion of the treating physician.
EP0060 will begin with Cohort 1, where at least 20 subjects ≥12 to <17 years of age will be 
enrolled to receive iv LCM. For the first 10 subjects in Cohort 1, iv LCM should be infused over 
a duration of 30 minutes but no longer than 60 minutes whenever possible. 
After completion of the first 10 subjects in Cohort 1, enrollment into Cohort 1 will be 
temporarily put on hold to allow for the DMC review of the safety and tolerability data from 
these subjects. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥8 to <12 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, enrollment into Cohort 2 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1 and Cohort 2. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 129 of 240
x OR Cohort 2 should be stopped, 
x AND whether Cohort 3 can be initiated.
For Cohort 3, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 3, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 3, enrollment into Cohort 3 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1, Cohort 2, and Cohort 3. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 3 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 3 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
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x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations.
Has been changed to:
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of 
intravenous (iv) lacosamide (LCM; VIMPAT®) infusions in pediatric subjects ≥4 to <17 years of 
age with epilepsy. Investigation the use of iv LCM in pediatric subjects with epilepsy ≥1 month 
to <4 years of age is planned. 
EP0060 will include approximately 75 subjects. The following subjects will be eligible for 
enrollment in EP0060:
x Open-label LCM (OLL) subjects: currently receiving oral LCM as adjunctive or 
monotherapy as participants in an open-label long-term study (SP848, EP0034, or other 
pediatric study).
x Prescribed-LCM (RxL) subjects: currently receiving prescribed oral LCM from 
commercial supply (eg, VIMPAT) as adjunctive or monotherapy.
x Initiating iv LCM (IIL) subjects: not currently receiving LCM and will receive iv LCM as 
adjunctive treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL 
subjects.
Subjects can receive iv LCM as follows: 
x Replacement for oral LCM treatment (OLL and RxL subjects): 
 Clinical need administration: Subjects currently taking prescribed oral LCM (or any 
enteric LCM administration, eg, LCM administration by feeding tube) who need to 
undergo a procedure and are treated at an epilepsy monitoring unit (EMU) or health 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 130 of 240
care facility, or other situations where iv administration is clinically appropriate and 
oral administration is not feasible (ie, surgery). In these subjects, the maximum 
number of iv doses of LCM is 10. 
 Elective administration: Subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) and elect to receive iv LCM 
administration at an EMU or healthcare facility. In these subjects, the maximum 
number of iv doses of LCM is 2.
x Adjunctive iv LCM treatment initiation (IIL subjects):
 Clinical need administration: Subjects not currently taking LCM who need to undergo 
a procedure, be treated at an EMU or health care facility, or other situations where iv 
administration is clinically appropriate and oral administration is not feasible (ie, 
surgery). In these subjects, the maximum number of iv doses of LCM is 10.
 Elective administration: Subjects not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
Pediatric subjects entering into EP0060 from the OLL group will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll into 
EP0060 from the RxL group will temporarily switch from their prescribed oral LCM treatment to 
the iv LCM formulation. Subjects in the IIL group will initiate adjunctive treatment with iv 
LCM. After completion of this study, eligible subjects from the RxL and IIL groups will have the 
option to continue LCM treatment in SP848. Subjects will be enrolled from approximately 40 
sites in North America and Europe. Additional sites or regions may be added if deemed 
necessary.
The primary objective of EP0060 is to evaluate the safety and tolerability of iv LCM infusion(s) 
in pediatric subjects ≥4 to <17 years with epilepsy. EP0060 is planned to include up to 
2 age-based cohorts with Cohort 1 including at least 40 subjects who are ≥8 to <17 years and 
Cohort 2 including at least 20 subjects who are ≥4 to <8 years. Within Cohort 1, at least 
20 subjects will be ≥12 to <17 years of age and at least 20 subjects will be ≥8 to <12 years of 
age. A Data Monitoring Committee (DMC) will review the safety and tolerability data for each 
cohort to make the following recommendations: the progression of the current cohort, including 
iv infusion durations to be evaluated, and progression to initiate enrollment in the next cohort 
(Cohort 2) or separate study for the evaluation of iv LCM in children <4 years of age (as detailed 
further below). 
EP0060 is comprised of the following study periods: 
x For all subjects:
 Screening and/or Baseline Period (up to 7 days),
 Treatment Period
(1) Clinical need administration: up to 10 doses or up to 5 days
(2) Elective administration: up to 2 consecutive doses over approximately 24 hours
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 131 of 240
 End-of-Study/Telephone Contact 1 (1 to 3 days),
x 
Additional visits or contacts as follows:
 RxL and IIL subjects who are eligible and choose to continue oral LCM treatment for 
up to 2 years in SP848
◦ 
Transition Visit, which can be concurrent with Final Visit or separate (up to 
7 days after Final Visit)
 RxL and IIL subjects who do not continue LCM treatment in SP848
◦ 
End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM). 
For all subjects, the Screening, Baseline, Treatment Period, and Final Visit may occur in 1 day, 
provided the subject only requires 1 iv infusion, results of examinations (ie, 12-lead 
electrocardiogram [ECG], laboratory measurements) are available to allow verification of subject 
eligibility prior to infusion, and time permits for completion of Final Visit assessments. 
If further time is required for Screening assessments or to obtain results, the Screening Period 
can last up to 7 days. For OLL and RxL subjects, oral LCM will be administered during this time 
from their open-label study or prescribed LCM supply in accordance with each subject’s oral 
LCM dosage regimen. For IIL subjects, no LCM will be administered during the Screening 
Period.
During the Treatment Period, at least 1 dose of iv LCM will be administered. If more than 
1 infusion is given, infusions will occur twice daily (bid) at approximately 12-hour intervals for 
up to 10 doses (or up to 5 days for clinical need administration or up to 2 consecutive doses (over 
approximately 24 hours) for elective administration. For OLL and RxL subjects, the daily dose 
of iv LCM will be the same as the subject's current stable daily dose of oral LCM (2 to 
12mg/kg/day or 100 to 600mg/day). The maximum dose permitted in this study for OLL and 
RxL subjects is 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, the iv LCM 
dose will be 1mg/kg (subjects weighing <50kg) or 50mg (subjects weighing ≥50kg). The total 
LCM daily dose for IIL subjects should be 2mg/kg/day (subjects weighing <50kg) or 100mg/day 
(subjects weighing ≥50kg) and should remain constant for at least 7 days prior to a LCM dose 
increase. 
During the Treatment Period, blood samples will be obtained for pharmacokinetic (PK) analysis, 
and detailed safety assessments will be performed. 
The timing of the End-of-Study/Final Visit will depend on the timing of the last LCM infusion or 
withdrawal from the Treatment Period and available time to complete all assessments. The Final 
Visit can be conducted on the same day as the last dose if the last LCM infusion was performed 
in the morning, and time permits completion of assessments. Otherwise, the Final Visit should be 
conducted the day following the last dose of iv LCM after completion of or withdrawal from the 
Treatment Period. The safety follow-up Telephone Contact 1 should occur 1 to 3 days after the 
Final Visit for all subjects. 
For RxL and IIL subjects who are eligible and choose to continue LCM treatment in SP848, a 
Transition Visit will be conducted either concurrent with the Final Visit or separately. Oral LCM 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 132 of 240
solution will be provided for these subjects to allow continuity of LCM therapy after the final 
LCM infusion and the subject’s Transition Visit in EP0060 and Visit 1 for SP848.
For RxL and IIL subjects who will not continue LCM treatment in SP848, an additional safety 
follow-up Telephone Contact 2 should occur 30 days (±2 days) after the last iv dose of study 
LCM treatment.
The maximum study durations are as follows:
x Approximately 16 days:
 Subjects in the OLL group will resume participation in their respective study and 
either resume oral LCM treatment or follow taper regimen as described in the long-
term, open-label study accordingly.
x Approximately 23 days
 Subjects in the RxL or IIL groups who, if determined clinically appropriate, are given 
the option to continue oral LCM treatment in SP848.
x Approximately 45 days:
 Subjects in the RxL or IIL groups who will not continue oral LCM treatment in 
SP848. 
Subjects should continue antiepileptic drug (AED) treatment at the discretion of the treating 
physician. For RxL and IIL subjects who will discontinue use of LCM, the subject should 
complete the EP0060 Final Visit and either refer to the long-term, open-label studies taper 
regimen or taper at the discretion of the treating physician.
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the Investigator, Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
Investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes. 
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 133 of 240
For Cohort 2, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the Investigator, Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
Investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes. 
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes. 
x OR Cohort 2 should be stopped,
x AND whether to initiate the assessment of safety in younger pediatric subjects (≥1 month to 
<4 years of age).  
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. A completer for this study is 
defined as a subject who completes at least 1 visit with iv LCM treatment and the associated 
assessments for that visit (eg, PK samples, vital signs, 12-lead ECG).
Change #8
Section 2 INTRODUCTION, first paragraph
Epilepsy is the second most prevalent neurological disorder in the world. More than 40 million 
people suffer from epilepsy–about 1% of the world’s population (Dichek, 1999). Although some 
forms of epilepsy may respond to surgical treatment and others may not require any treatment at 
all, most patients with epilepsy require appropriate pharmacological therapy (Perucca, 1996). 
The Institute of Medicine of the National Academies recently provided a review of the burdens 
of epilepsy, global incidence and prevalence of epilepsy, classification systems for seizure types 
and syndromes, gaps in information about epilepsy, and general recommendations (Institute of 
Medicine, 2012). In the past 2 decades, several new options for the medical treatment of epilepsy 
have been introduced, including novel AEDs and vagus nerve stimulation (VNS).
Has been changed to:
Epilepsy is the second most prevalent neurological disorder in the world. It is estimated that 
almost 70 million people suffer from epilepsy (Ngugi et al, 2011). Although some forms of 
epilepsy may respond to surgical treatment and others may not require any treatment at all, most 
patients with epilepsy require appropriate pharmacological therapy (Perucca, 1996). The Institute 
of Medicine of the National Academies recently provided a review of the burdens of epilepsy, 
global incidence and prevalence of epilepsy, classification systems for seizure types and 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 134 of 240
syndromes, gaps in information about epilepsy, and general recommendations (Institute of 
Medicine, 2012). In the past 2 decades, several new options for the medical treatment of epilepsy 
have been introduced, including novel AEDs and vagus nerve stimulation (VNS).
Change #9
Section 2 INTRODUCTION, fifth paragraph
Intravenous formulations are particularly helpful as short-term replacement of oral formulations 
for patients unable to take oral products (eg, preoperative and postoperative patients, patients 
with acute gastrointestinal disorders). Such formulations allow patients to be maintained on the
same AED on their stable dose when they are unable to take the drug orally.
Has been changed to:
Intravenous formulations are particularly helpful as short-term replacement of oral formulations 
for patients unable to take oral products (eg, preoperative and postoperative patients, patients 
with acute gastrointestinal disorders). Such formulations allow patients to be maintained on the 
same AED on their stable dose when they are unable to take the drug orally. Intravenous 
formulations may also be helpful in the initiation of treatment in certain situations when the 
patient is unable to take oral medications.
Change #10
Section 2 Introduction, sixth paragraph
The iv formulation of LCM is approved in the US, EU, and several countries worldwide at doses 
of 200 to 400mg/day as adjunctive therapy in the treatment of partial-onset seizures in subjects 
with epilepsy when oral administration is temporarily not feasible. Intravenous LCM is approved 
in patients ≥16 years of age and for infusion durations of 15 to 60 minutes depending on the 
country-specific labeling.
Has been changed to: 
In the US, the iv formulation of LCM is approved in patients ≥17 years of age at a maximum 
dose of 400mg/day as monotherapy and adjunctive therapy in the treatment of partial onset 
seizures in subjects with epilepsy when oral administration is temporarily not feasible. In EU, the 
iv formulation is approved in patients ≥16 years at a maximum dose of 600mg/day as 
monotherapy (EU CHMP positive opinion received on 11 Nov 2016) and at a maximum dose of 
400mg/day as adjunctive therapy in the treatment of partial onset seizures in subjects with 
epilepsy when oral administration is temporarily not feasible. Intravenous LCM is approved in 
patients ≥16 years of age and for infusion durations of 15 to 60 minutes depending on the 
country-specific labeling.
Change #11
Section 2 INTRODUCTION, new seventh paragraph
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 135 of 240
Recently, a retrospective evaluation was conducted to examine the use of iv LCM in 47 infants 
and children from 4 months to <12 years of age (Arkilo et al, 2016). The median age across the 
47 children was 6.5 years, and 18 children were <3 years of age. Intravenous LCM was 
administered as adjunctive treatment along with ≥2 other AED. Lacosamide dose levels ranged 
from 1 to 11mg/kg, and the infusion was given over 30 minutes. Fifteen of the children were 
administered iv LCM either as replacement treatment for oral maintenance dose (n=10) or to 
initiate maintenance dose (n=5). For the remaining children, iv LCM was used to treat acute 
exacerbation of seizure frequency (n=18), status epilepticus (n=11) or epilepsia partialis continua 
(n=3). Children were observed for at least 48 hours after infusion. The 11 children with status 
epilepticus were not able to respond to inquiries about adverse effects. Of the remaining 
36 subjects, 5 experienced adverse effect of sedation which resolved in all 5 within 24 hours. No 
other observable adverse effects were noted. No cardiac events were noted during the infusions 
for the 80% of children who had ECG evaluation during the infusion. This study shows an initial 
positive benefit-risk profile for the use of iv LCM in infants and children from 4 months to 
<12 years of age. 
Has been added
Change #12
Section 2 INTRODUCTION, seventh paragraph (now eighth paragraph)
The results of EP0060 will provide safety, tolerability, and PK data regarding the use of the 
iv LCM formulation as replacement for oral LCM in pediatric subjects ≥4 to <17 years with 
epilepsy.
Has been changed to:
The results of EP0060 will provide safety, tolerability, and PK data regarding the use of the 
iv LCM formulation either as replacement for oral LCM or for adjunctive LCM treatment 
initiation in pediatric subjects ≥4 to <17 years with epilepsy.
Change #13
Section 3 STUDY OBJECTIVE(S)
The primary objective of this study is to evaluate the safety and tolerability of iv LCM 
infusion(s) in pediatric subjects ≥4 to <17 years with epilepsy, after temporarily switching from 
the equivalent stable oral LCM dose. An additional objective is to evaluate the PK of iv LCM 
replacement in pediatric subjects with epilepsy. 
Has been changed to:
The primary objective of this study is to evaluate the safety and tolerability of iv LCM 
infusion(s) in pediatric subjects ≥4 to <17 years with epilepsy. An additional objective is to 
evaluate the PK of iv LCM in pediatric subjects with epilepsy.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 136 of 240
Change #14
Section 4.1 Primary variable(s) (now Primary safety variables)
Safety and tolerability will be assessed using the following primary variables:
x Adverse events (AEs) reported spontaneously by the subject and/or caregiver (including 
parent/legal guardian) or observed by the investigator
x Subject withdrawals due to AEs
x Changes in 12-lead electrocardiograms (ECGs)
x Changes in vital sign measurements (blood pressure [BP] and pulse rate) 
Has been changed to:
Safety and tolerability will be assessed using the following primary variables:
x Adverse events (AEs) reported spontaneously by the subject and/or caregiver (including 
parent/legal guardian) or observed by the investigator
x Subject withdrawals due to AEs
Change #15
Section 4.2 Other safety variables
Other safety variables include the following:
x Changes in 12-lead electrocardiograms (ECGs)
x Changes in vital sign measurements (blood pressure [BP] and pulse rate)
x Changes in physical examinations
x Changes in neurological examinations
Has been added. 
This change also shifted the numbering of the Section describing the Pharmacokinetic variables 
from Section 4.2 to Section 4.3.
Change #16
Section 5.1 Study description
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of iv 
LCM infusions as replacement for oral LCM in pediatric subjects ≥4 to <17 years of age with 
epilepsy. EP0060 will include subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) who need to undergo a procedure, be 
admitted to an EMU or health care facility, or other situations where iv administration is 
clinically appropriate. Approximately 75 subjects, who are participating in long-term, open-label 
studies with LCM or who are currently prescribed VIMPAT, will be enrolled. Pediatric subjects 
entering into EP0060 from a long-term, open-label study will temporarily suspend their 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 137 of 240
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll directly 
into EP0060 will temporarily switch from their prescribed oral VIMPAT treatment to the iv 
LCM formulation. Subjects will not be prescribed or maintained on VIMPAT for the purposes of 
participating in EP0060. Subjects will be enrolled from approximately 40 sites in North America, 
Europe, Asia Pacific, and Latin America. Additional sites or regions may be added if deemed 
necessary.
EP0060 is planned to include up to 3 age-based cohorts of at least 20 subjects per cohort: ≥12 to 
<17 years (Cohort 1), ≥8 to <12 years (Cohort 2), and ≥4 to <8 years (Cohort 3). A DMC will 
review the safety and tolerability data for each cohort to make recommendations for the 
progression of subsequent cohort enrollment and iv infusion durations to be evaluated. Details 
regarding the DMC are provided in Section 12.7.2.
EP0060 is comprised of the following study periods: 
x Screening and/or Baseline Period (up to 7 days),
x Treatment Period (up to 5 days),
x End-of-Study/Final Visit (1 day), 
x End-of-Study/Telephone Contact (1 to 2 days). 
During the Screening Period (Day -7 to Day -1), oral LCM will be administered in accordance 
with each subject’s oral LCM dosage regimen. For subjects enrolled in a long-term, open-label 
study, the oral LCM will be administered from the long-term, open-label study supply. For 
subjects prescribed VIMPAT and enrolling directly into EP0060, oral LCM will be administered 
from the subject’s prescribed VIMPAT supply. 
Subjects will be under medical care at a healthcare facility for the duration of the iv LCM 
infusion treatment in EP0060. If necessary, the Screening and/or Baseline Visit can occur on the 
same day as the first iv LCM infusion. In this case, it is required that all screening procedures are 
performed and the results of examinations (ie, ECG) are available to allow verification of subject 
eligibility. During the Treatment Period, subjects will receive iv LCM infusion bid at 
approximately 12-hour intervals for up to 5 days. The daily dose of iv LCM will be the same as 
the subject's current stable bid dose of oral LCM (2 to 12mg/kg/day or 100 to 600mg/day). 
During the Treatment Period, blood samples will be obtained for PK analysis, and safety 
assessments will be performed (physical and neurological exams, pulse rate, BP, 12-lead ECG, 
clinical hematology and chemistry, and Columbia-Suicide Severity Rating Scale [C-SSRS] when 
applicable). An End-of-Study/Final Visit will be conducted the day after the last dose of iv LCM 
after completion of or withdrawal from the Treatment Period. A safety follow-up Telephone 
Contact should occur 1 to 2 days after the End-of-Study/Final Visit.
The maximum study duration for an individual subject will be approximately 15 days. After 
completion of or discontinuation from EP0060, subjects who enrolled into EP0060 from a 
long-term, open-label study will resume their participation in that study and resume oral LCM 
treatment accordingly. Subjects who were prescribed VIMPAT should continue AED treatment 
at the discretion of the treating physician.
The schedule of study assessments is provided in Section 5.2.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 138 of 240
EP0060 will begin with Cohort 1, where at least 20 subjects ≥12 to <17 years of age will be 
enrolled to receive iv LCM. For the first 10 subjects in Cohort 1, iv LCM should be infused over 
a duration of 30 minutes but no longer than 60 minutes whenever possible. 
After completion of the first 10 subjects in Cohort 1, enrollment into Cohort 1 will be 
temporarily put on hold to allow for the DMC review of the safety and tolerability data from 
these subjects. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥8 to <12 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, enrollment into Cohort 2 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1 and Cohort 2. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 2 should be stopped, 
x AND whether Cohort 3 can be initiated.
For Cohort 3, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 3, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 3, enrollment into Cohort 3 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1, Cohort 2, and Cohort 3. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 3 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 3 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 3 should be stopped, 
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).  
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30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 139 of 240
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. 
Has been changed to:
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of iv 
LCM infusions in pediatric subjects ≥4 to <17 years of age with epilepsy. EP0060 will include 
approximately 75 subjects. The following subjects will be eligible for enrollment in EP0060:
x OLL subjects: currently receiving oral LCM as adjunctive or monotherapy as participants 
in an open-label long-term study (SP848, EP0034, or other pediatric study).
x RxL subjects: currently receiving prescribed oral LCM from commercial supply (eg, 
VIMPAT) as adjunctive or monotherapy.
x IIL subjects: not currently receiving LCM and will receive iv LCM as adjunctive 
treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL subjects.
Subjects can receive iv LCM as follows:
x Replacement for oral LCM treatment (OLL and RxL subjects): 
 Clinical need administration: subjects currently taking prescribed oral LCM (or any 
enteric LCM administration, eg, LCM administration by feeding tube) who need to 
undergo a procedure and are treated at an EMU or health care facility, or other 
situations where iv administration is clinically appropriate and oral administration is 
not feasible (ie, surgery). In these subjects, the maximum number of iv doses of LCM 
is 10.
 Elective administration: subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) and elect to receive iv LCM 
administration at an EMU or healthcare facility. In these subjects, the maximum 
number of iv doses of LCM is 2. 
x Adjunctive iv LCM treatment initiation (IIL subjects):
 Clinical need administration: subjects not currently taking LCM who need to undergo 
a procedure, be treated at an EMU or health care facility, or other situations where iv 
administration is clinically appropriate and oral administration is not feasible (ie, 
surgery). In these subjects, the maximum number of iv doses of LCM is 10.
 Elective administration: subjects not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
Pediatric subjects entering into EP0060 from the OLL group will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll into 
EP0060 from the RxL group will temporarily switch from their prescribed oral LCM treatment to 
the iv LCM formulation while subjects in the IIL group will initiate adjunctive treatment with iv 
LCM. After completion of this study, eligible subjects from the RxL and IIL groups will have the 
option to continue LCM treatment in SP848. Subjects will be enrolled from approximately 40 
sites in North America and Europe. Additional sites or regions may be added if deemed 
necessary.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 140 of 240
EP0060 is planned to include up to 2 age-based cohorts with Cohort 1 including at least 
40 subjects who are ≥8 to <17 years and Cohort 2 including at least 20 subjects who are ≥4 to 
<8 years. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age and at least 
20 subjects will be ≥8 to <12 years of age. A DMC will review the safety and tolerability data for 
each cohort to make the following recommendations: the progression of the current cohort, 
including iv infusion durations to be evaluated, and progression to initiate enrollment in the next 
cohort (Cohort 2) or separate study for the evaluation of iv LCM in children <4 years of age. 
Details regarding the DMC are provided in Section 12.7.2.
EP0060 is comprised of the following study periods: 
x For all subjects:
 Screening and/or Baseline Period (up to 7 days),
 Treatment Period
(1) Clinical need administration (see above in this Section): up to 10 doses or up to 5 
days
(2) Elective administration (see above in this Section): up to 2 consecutive doses over 
approximately 24 hours
 End-of-Study/Final Visit (1 day), 
 End-of-Study/Telephone Contact 1 (1 to 3 days),
x 
Additional visits or contacts as follows:
 RxL and IIL subjects who are eligible and choose to continue oral LCM treatment for 
up to 2 years in SP848
◦ 
Transition Visit, which can be concurrent with Final Visit or separate (up to 7 
days after Final Visit)
 RxL and IIL subjects who do not continue LCM treatment in SP848
◦ 
End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM).
For all subjects, the Screening, Baseline, Treatment Period, and Final Visit may occur in 1 day, 
provided the subject only requires 1 iv infusion, results of examinations (ie, ECG, laboratory 
measurements) are available to allow verification of subject eligibility prior to infusion, and time 
permits for completion of Final Visit assessments. 
If further time is required for Screening assessments or to obtain results, the Screening Period 
can last up to 7 days. For OLL and RxL subjects, oral LCM will be administered during this time 
from their open-label study or prescribed LCM supply in accordance with each subject’s oral 
LCM dosage regimen. For IIL subjects, no LCM will be administered during the Screening 
Period.
During the Treatment Period, at least 1 dose of iv LCM will be administered. If more than 
1 infusion is given, infusions will occur twice daily (bid) at approximately 12-hour intervals for 
up to 10 doses (or up to 5 days) for clinical need administration or up to 2 consecutive doses 
(over approximately 24 hours) for elective administration. For OLL and RxL subjects, the daily 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 141 of 240
dose of iv LCM will be the same as the subject's current stable daily dose of oral LCM (2 to 
12mg/kg/day or 100 to 600mg/day). The maximum dose permitted in this study for OLL and 
RxL subjects is 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, the iv LCM 
dose will be 1mg/kg (subjects weighing <50kg) or 50mg (subjects weighing ≥50kg). The total 
LCM daily dose for IIL subjects should be 2mg/kg/day (subjects weighing <50kg) or 100mg/day 
(subjects weighing ≥50kg) and should remain constant for at least 7 days prior to a LCM dose 
increase. 
During the Treatment Period, blood samples will be obtained for PK analysis, and safety 
assessments will be performed (AEs, physical and neurological exams, pulse rate, BP, 12-lead 
ECG, clinical hematology and chemistry, and Columbia-Suicide Severity Rating Scale [C-SSRS] 
when applicable). 
The timing of the End-of-Study/Final Visit will depend on the timing of the last LCM infusion or 
withdrawal from the Treatment Period and available time to complete all assessments. The Final 
Visit can be conducted on the same day as the last dose if the last LCM infusion was performed 
in the morning, and time permits completion of assessments. Otherwise, the Final Visit should be 
conducted the day following the last dose of iv LCM after completion of or withdrawal from the 
Treatment Period. The safety follow-up Telephone Contact 1 should occur 1 to 3 days after the 
Final Visit for all subjects. 
For RxL and IIL subjects who are eligible and choose to continue LCM treatment in SP848, a 
Transition Visit will be conducted either concurrent with the Final Visit or separately. Oral LCM 
solution will be provided for these subjects to allow continuity of LCM therapy after the final 
LCM infusion and the subject’s Transition Visit in EP0060 and Visit 1 for SP848. 
For RxL and IIL subjects who will not continue LCM treatment in SP848, an additional safety 
follow-up Telephone Contact 2 should occur 30 days (±2 days) after the last iv dose of study 
LCM treatment.
The maximum study durations are as follows:
x Approximately 16 days:
 Subjects in the OLL group will resume participation in their respective study and 
either resume oral LCM treatment or follow taper regimen as described in the long-
term, open-label study accordingly.
x Approximately 23 days
 Subjects in the RxL or IIL groups who, if determined clinically appropriate, are given 
the option to continue oral LCM treatment in SP848.
x Approximately 45 days:
 Subjects in the RxL or IIL groups who will not continue oral LCM treatment in 
SP848. 
Subjects should continue AED treatment at the discretion of the treating physician. For RxL and 
IIL subjects who directly enrolled and will discontinue use of LCM, the subject should complete 
the EP0060 Final Visit and either refer to the long-term, open-label studies taper regimen or 
taper at the discretion of the treating physician.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 142 of 240
The schedule of study assessments is provided in Section 5.2.
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the Investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
Investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes.
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the Investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
Investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes.
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR Cohort 2 should be stopped, 
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).  
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. A completer for this study is 
defined as a subject who completes at least 1 visit with iv LCM treatment and the associated 
assessments for that visit (eg, PK samples, vital signs, 12-lead ECG).
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 143 of 240
Change #17
Section 5.1.1 Study duration per subject, first paragraph
The maximum iv LCM exposure per subject will be up to 5 days with a total study duration of up 
to 15 days (up to 7 days for screening, up to 5 days of treatment, 1 day for discharge/Final Visit, 
and a safety follow-up Telephone Contact 1 to 2 days after the Final Visit).
Has been changed to:
For clinical need administration, the planned maximum iv LCM exposure will be up to 10 doses 
(or up to 5 days). For elective administration, the planned maximum iv LCM exposure will be up 
to 2 consecutive doses (over approximately 24 hours). 
For OLL subjects, the planned maximum total study duration assuming clinical need 
administration will be approximately 16 days (up to 7 days for screening, up to 5 days of 
treatment, 1 day for discharge/Final Visit, and a safety follow-up Telephone Contact 1 at 1 to 3 
days after the Final Visit). 
For RxL and IIL subjects who will continue LCM treatment in SP848, the planned maximum 
total study duration assuming clinical need administration will be approximately 23 days to 
allow arrangement for assessments to transition to SP848 (up to 7 days for screening, up to 
5 days of treatment, 1 day for discharge/Final Visit, safety follow-up Telephone Contact 1 at 1 to 
3 days after the Final Visit, and the Transition Visit at 1 to 7 days after the last dose). The Final 
Visit and the Transition Visit may occur on the same day or separate days, depending on 
availability and scheduling.
For RxL and IIL subjects who will not continue LCM treatment in SP848, the planned maximum 
total study duration (assumes clinical need administration) will be approximately 45 days to 
allow for further safety follow-up (up to 7 days for screening, up to 5 days of treatment, 1 day for 
discharge/Final Visit, safety follow-up Telephone Contact 1 at 1 to 2 days after the Final Visit, 
and safety follow-up Telephone Contact 2 at 30 days [±2 days] after the last dose).
For those subjects electively receiving iv LCM, the above maximum total study durations are 
reduced by 4 days. 
Change #18
Section 5.1.2 Planned number of subjects and site(s)
Approximately 75 subjects currently participating in long-term, open-label studies with LCM or 
who are currently prescribed VIMPAT will be enrolled at approximately 40 sites.
The following cohorts are planned:
x Cohort 1: at least 20 subjects from ≥12 to <17 years of age
x Cohort 2: at least 20 subjects from ≥8 to <12 years of age
x Cohort 3: at least 20 subjects from ≥4 to <8 years of age 
The remaining subjects may be enrolled in any of the 3 cohorts.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 144 of 240
Has been changed to:
Approximately 75 subjects will be enrolled at approximately 40 sites.
The following cohorts are planned:
x Cohort 1: at least 40 subjects from ≥8 to <17 years of age, with at least 20 subjects from 
≥12 to <17 years of age and at least 20 subjects from ≥8 to <12 years of age
x Cohort 2: at least 20 subjects from ≥4 to <8 years of age 
The remaining subjects may be enrolled in either of the 2 cohorts.
Change #19
Section 5.1.3 Anticipated regions and countries
The study will be conducted at selected sites from North America, Europe, Asia Pacific, and 
Latin America. Additional sites may be added as deemed necessary.
Has been changed to:
The study will be conducted at selected sites from North America and Europe. Additional sites 
may be added as deemed necessary.
Change #20
Table 5-1
Schedule of study assessments
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 145 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitc
End-of-Study Period
Visit
V1a
V1ba
V2
V3b
Final Visitd
TCe
Study Day
-7 to -1
-1
1
2 to 5
2 to 6
2 to 9
Written informed consent
X
Inclusion/exclusion criteria
X
Xf
Demographics
X
Medical procedures
X
X
X
X
X
X
X
Procedure historyg
X
Medical history/updateg
X
X
X
X
X
X
X
Diagnosis of epilepsyg
X
Childbearing potentialg
X
LCM dosing historyh
X
Prior and concomitant medicationsi
X
X
X
X
X
X
X
Concomitant AEDs/VNS settings 
X
X
X
X
X
X
Pregnancy testingj
X
X
Withdrawal criteria
X
X
X
X
X
X
AE reportingk
X
X
X
X
X
X
X
ILAE seizure classification 
X
Physical examination (complete)
X
X
Neurological examination (complete)
X
X
Clinical chemistry and hematologyl
X
X
X
X
12-lead ECG
X
Xm
Xm
Xm
X
X
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 146 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitc
End-of-Study Period
Visit
V1a
V1ba
V2
V3b
Final Visitd
TCe
Study Day
-7 to -1
-1
1
2 to 5
2 to 6
2 to 9
Vital signs
X
Xn
Xn
Xn
X
X
Body weight and height
X
PK blood samplingo
X
X
X
Admission to the unitp
X
X
Oral LCM administrationq
X
X
X
X
Intravenous LCM infusionr
X
X
X
C-SSRSs
X
Xt
X
X
Xc
X
Discharge from the unit
X
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; C-SSRS=Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; 
ILAE=International League against Epilepsy; iv=intravenous; LCM=lacosamide; PK=pharmacokinetics; TC=Telephone Contact; V=Visit; VNS=vagus 
nerve stimulation
a Visit 1b only applies when Screening and Baseline occur on separate days. 
b If iv LCM treatment is continued after Day 1, assessments for Visit 3 must be completed each day of iv LCM treatment in EP0060. 
c If an Unscheduled Visit is needed, the assessments noted will be performed. Additional assessments can be performed at the investigator’s discretion. The 
C-SSRS assessment should be completed if the Unscheduled Visit is due to an AE.
d A Final Visit must be completed the day after the last dose of iv LCM for all subjects who complete or withdraw prematurely from EP0060. For subjects 
who will discontinue use of LCM, the subject should complete the EP0060 Final Visit and refer to the long-term, open-label studies taper regimen.
e The Telephone Contact assessment should be performed 1 to 2 days after the Final Visit (2 to 7 days after Visit 2/Day 1). During the contact, the site 
should inquire as to whether the subject noted any change at the site of the infusion.
f Verification that the subject continues to meet inclusion/exclusion criteria if Screening and Baseline occur on separate days.
g Procedure history, medical history, diagnosis of epilepsy, and childbearing potential will be collected for direct-enroll subjects who were prescribed 
VIMPAT prior to entering the study. Medical history update will be collected for subjects from the long-term open-label studies. 
h Lacosamide dosing history will include date, time, and dosage information during the last 3 days.
i Prior medications will only be collected for direct-enroll subjects. Concomitant medications from the long-term open-label studies will be followed, as well 
as the recording of new concomitant medications during EP0060 for all enrolled subjects.
j Pregnancy testing for subjects of childbearing potential will be serum testing at the Screening Visit for direct-enroll subjects who are prescribed VIMPAT 
and urine testing for subjects enrolled in long-term, open-label studies. Urine pregnancy testing (or serum pregnancy test if no urine sample can be 
REDA
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 147 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitc
End-of-Study Period
Visit
V1a
V1ba
V2
V3b
Final Visitd
TCe
Study Day
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obtained) will be conducted on all subjects of childbearing potential at the Final Visit. 
k Ongoing AEs from the long-term open-label studies will be followed, as well as recording of new AEs during EP0060. 
l Laboratory assessments will be performed for subjects who are directly enrolled into EP0060. Screening laboratory assessments may be conducted up to 
the day of the infusion provided they are reviewed and meet inclusion/exclusion criteria prior to the infusion.
m 12-lead ECG will be performed approximately 20 minutes prior to each infusion and at approximately 15, 30, 60 minutes, and 2 hours from the start of 
each iv administration. Care should be taken to assure proper lead placement and quality ECG recordings. Subjects should be at rest at least 5 minutes prior 
to each ECG recording and should be motionless during the recording, when feasible.
n Vital signs will be performed approximately 10 minutes prior to each infusion and at approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of 
each iv administration. Noninvasive BP (systolic and diastolic) and pulse rate will be measured at study visits after at least 3 minutes at rest, when feasible.
o Samples for PK will be drawn after ECG and vital signs have been taken. Plasma samples will be obtained from the opposite arm in which the solution for 
infusion was administered for the first iv LCM infusion (Day 1): predose (within 1 hour prior to iv LCM infusion) and postdose (within 1 to 4 hours after 
end of iv LCM infusion), and for the final iv LCM infusion (Day 2 to 5/Early Termination): predose (within 1 hour prior to iv LCM infusion) and postdose 
(within 1 to 4 hours after end of iv LCM infusion). Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in 
the event of a relevant treatment-emergent AE.
p Admission to the health care facility to participate in the study should take place at least the day prior to the start of the first iv LCM infusion. However, 
when necessary for the wellbeing of the subject or when the investigator deems it appropriate, the admission to the health care facility and the first iv LCM 
infusion can start on the same day.
q On Day -1, oral LCM will be administered in accordance with each subject’s LCM dosage regimen. 
r LCM will be administered twice daily at approximately 12-hour intervals, once in the morning and once in the evening, for up to 5 days.
s All subjects ≥6 years of age will complete the “Baseline/Screening” version of the C-SSRS at Visit 1 and will complete the “Since Last Visit” version at 
subsequent visits. If a subject becomes 6 years of age during the study, the "Already Enrolled" version of the C-SSRS should be used at the first visit at 
which the subject is 6 years of age and the “Since Last Visit” version used at subsequent visits. 
t The C-SSRS assessment (see Section 10.7.5 ) does not need to be completed twice if Screening/Baseline assessments are done on the same day.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 148 of 240
Has been changed to:
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitd
End-of-Study Period
Visit
V1aa
V1bb
V2
V3c
Final 
Visite
TC1f
Transition 
Visitg
TC2h
Study Day
-7 to 
1
-1 to 
1
1
2 to 5
1 to 6
2 to 9
1 to 13
29 to 
37
Written informed consent
X
Inclusion/exclusion criteria
X
Xi
Demographics
X
Medical procedures
X
X
X
X
X
X
X
X
Procedure historyj
X
Medical history/updatej
X
X
Diagnosis of epilepsyj
X
Seizure historyk
X
Childbearing potentialj
X
LCM dosing historyl
X
X
LCM dosing information since 
Treatment Period
X
X
X
Prior and concomitant medicationsm
X
X
X
X
X
X
X
X
X
Concomitant AEDs/VNS settings/ 
ketogenic diet 
X
X
X
X
X
X
Xn
Xn
Urine pregnancy testing (as 
applicable)
X
X
X
Withdrawal criteria
X
X
X
X
X
X
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 149 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitd
End-of-Study Period
Visit
V1aa
V1bb
V2
V3c
Final 
Visite
TC1f
Transition 
Visitg
TC2h
Study Day
-7 to 
1
-1 to 
1
1
2 to 5
1 to 6
2 to 9
1 to 13
29 to 
37
AE reporting
X
X
X
X
X
X
X
X
X
Physical examination (complete)
X
X
Physical examination (brief)
X
Xo
Xo
X
Neurological examination 
(complete)
X
X
Neurological examination (brief)
X
Xo
Xo
X
Clinical chemistry and hematologyp
X
Xq
X
12-lead ECG
X
X
Xr
Xr
X
Vital signs
X
X
Xs
Xs
X
X
Body weight and height
X
PK blood sampling
Xt
Xu
Intravenous LCM infusionv
X
X
C-SSRSw
X
Xx
Xo
Xo
Xd
X
Additional items for RxL and IIL subjects continuing into SP848
Dispense transitional supply of 
oral LCM solutiong
Xy
Collect transitional supply of 
oral LCM solution
X
Visit 1 SP848 assessments 
(documented in SP848) 
X
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 150 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitd
End-of-Study Period
Visit
V1aa
V1bb
V2
V3c
Final 
Visite
TC1f
Transition 
Visitg
TC2h
Study Day
-7 to 
1
-1 to 
1
1
2 to 5
1 to 6
2 to 9
1 to 13
29 to 
37
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; C-SSRS=Columbia-Suicide Severity Rating Scale; ECG=electrocardiogram; IIL=initiating iv 
LCM; iv=intravenous; LCM=lacosamide; OLL=open-label LCM; PK=pharmacokinetics; RxL=prescribed commercial LCM; TC=Telephone Contact; V=Visit; 
VNS=vagus nerve stimulation
a
The Screening and/or Baseline Visit can occur on the same day as the first iv LCM infusion, if necessary. In this case, it is required that all Screening 
procedures are performed and the results of examinations (ie, ECG, laboratory measurements) are available to allow verification of subject eligibility.
b
Visit 1b only applies when Screening and Baseline occur on separate days. 
c
If iv LCM treatment is continued after Day 1, assessments for Visit 3 must be completed for each infusion of iv LCM treatment in EP0060, unless otherwise 
noted (see footnote o).  
d
If an Unscheduled Visit is needed, the assessments noted will be performed. Additional assessments can be performed at the investigator’s discretion. If the 
Unscheduled Visit is due to an AE, the C-SSRS assessment should be completed and collection of a blood sample for LCM PK analysis is at the discretion 
of the investigator.
e
A Final Visit must be completed for all subjects who complete or withdraw prematurely from EP0060. If the last iv infusion of LCM for the study occurs in 
the morning, the Final Visit may occur on the same day as the last infusion, time permitting. Otherwise, the Final Visit should occur on the following day 
(ie, last infusion in evening). For subjects who will discontinue use of LCM, the subject should complete the EP0060 Final Visit and either refer to the 
long-term, open-label studies taper regimen or taper at the discretion of the treating physician for those subjects who enrolled directly.
f
The Telephone Contact 1 Visit assessment should be performed 1 to 3 days after the Final Visit. During the contact, the site should inquire as to whether the 
subject noted any change at the site of the infusion.
g
The Transition Visit will only be conducted for RxL and IIL subjects who will continue LCM treatment in SP848. This visit can occur at the same time as 
the Final Visit or on another day up to and including 7 days after the Final Visit and should occur at the same time as Visit 1 for SP848. 
h
The Telephone Contact 2 Visit will only be conducted for RxL and IIL subjects who will not continue LCM treatment in SP848.
i
Verification that the subject continues to meet inclusion/exclusion criteria if Screening and Baseline occur on separate days.
j
Procedure history, medical history, diagnosis of epilepsy, and childbearing potential will be collected for RxL and IIL subjects at Screening. For OLL 
subjects, a medical history update will be performed in order to collect medical history that was not captured during the course of the prior study. 
k
Subject or caregiver (including parent/legal guardian) will be asked how many seizures the subject has had over the past 4 weeks as a historical baseline for 
RxL and IIL subjects.
l
For OLL and RxL subjects, LCM dosing history will include date, time, and dosage information during the last 3 days.
m
Prior medications will only be collected for direct-enroll subjects. 
n
At Telephone Contact follow-up calls, only concomitant AED and ketogenic diet information will be gathered (ie, settings for VNS will not be gathered).
o
During the Treatment Period, brief physical examination, brief neurological examination, and C-SSRS should be performed once per day and after an 
infusion.
p
Screening laboratory assessments may be conducted up to and including the day of the infusion provided they are reviewed and meet inclusion/exclusion 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 151 of 240
Table 5‒1:
Schedule of study assessments
Assessments
Screening/
Baseline
Treatment Period
Unscheduled 
Visitd
End-of-Study Period
Visit
V1aa
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37
criteria prior to the infusion. For all subjects, local laboratory results obtained for routine diagnostic and medical care can be used whenever possible if 
collected no more than 24 hours prior to Screening/Baseline Visit in order to minimize blood loss associated with the study. Use of the central or local 
laboratory is at the discretion of the investigator for all visits except the Final Visit. The central laboratory must be used for laboratory samples collected at 
the Final Visit.
q
If Screening and Baseline Visits are not performed on the same day, repetition of laboratory assessments at Baseline is at the discretion of the investigator.
r
A 12-lead ECG will be performed approximately 20 minutes prior to each infusion and at approximately 15, 30, 60 minutes, and 2 hours from the start of 
each iv administration. Care should be taken to assure proper lead placement and quality ECG recordings. Subjects should be at rest (sitting or supine) at 
least 3 minutes prior to each ECG recording and should be motionless during the recording, when feasible.
s
Vital signs will be performed approximately 10 minutes prior to each infusion and at approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of 
each iv administration. Noninvasive BP (systolic and diastolic) and pulse rate will be measured at study visits after at least 3 minutes at rest, when feasible.
t
Plasma samples will be obtained from a different region of the body from the region in which the solution for infusion was administered for the first iv LCM 
infusion (Day 1): predose for OLL and RxL subjects (within 1 hour prior to iv LCM infusion) and postdose for all subjects (within 1 to 4 hours after end of 
iv LCM infusion). If the postdose PK sample is taken at a similar time for ECG and vital signs (ie, the 2 hour time point), the PK sample will be drawn after 
ECG and vital signs have been taken. Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in the event of a 
relevant treatment-emergent AE.
u
If the subject has more than 1 iv LCM infusion, it is optional to also collect plasma samples for the final iv LCM infusion (Day 2 to 5/Early Termination): 
predose for all subjects (within 1 hour prior to iv LCM infusion) and postdose for all subjects (within 1 to 4 hours after end of iv LCM infusion). If the 
postdose PK sample is taken at a similar time for ECG and vital signs (ie, the 2 hour time point), the PK sample will be drawn after ECG and vital signs 
have been taken. Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in the event of a relevant 
treatment-emergent AE.
v
During the Treatment Period subjects will receive at least 1 dose of iv LCM. If more than 1 infusion is needed, infusions will occur bid at approximately 
12-hour intervals up to either 2 doses (elective administration) or 10 doses (clinical need administration). 
w
All subjects ≥6 years of age will complete the “Baseline/Screening” version of the C-SSRS at Visit 1 and will complete the “Since Last Visit” version at 
subsequent visits. If a subject becomes 6 years of age during the study, the "Already Enrolled" version of the C-SSRS should be used at the first visit at 
which the subject is 6 years of age and the “Since Last Visit” version used at subsequent visits. If the subject is <6 years of age, assessment for signs of 
depression will be conducted as described in Section 10.7.5 of the protocol.
x
The C-SSRS assessment does not need to be completed twice if Screening/Baseline assessments are done on the same day. If Screening/Baseline and Visit 2 
occur on the same day, 2 assessments should be completed with 1 predose and 1 after infusion.
y
For RxL and IIL subjects who are eligible and wish to enroll in SP848, a short-term oral LCM solution will be dispensed to allow continuity of LCM 
treatment while visits and assessments are scheduled for starting SP848. Subjects (or their caregivers) will administer the oral LCM solution twice a day 
according to the investigator’s instructions until the subject returns for the Transition Visit.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 152 of 240
Change #21
Table 5-2 Timing of infusion, blood sampling, and measurement of vital signs and ECG on 
Treatment Days (Infusion Day 1 to Day 5)
Table 5-2:
Timing of infusion, blood sampling, and measurement of vital signs 
and ECG on Treatment Days (Infusion Day 1 to Day 5)
Approximate time points referred to 
iv infusion 
Vital signsa
12-lead ECGb
PK blood samplingc
-59min to -3min
X
-20min
X
-10min
X
T0 (start of infusion)
+5min
X
+10min
X
+15min
X
+20min
X
+30min
X
+45min
X
+60min
X
X
+1h to +4hd
X
+2h
X
X
AE=adverse event; BP=blood pressure; ECG=electrocardiogram; h=hours; iv=intravenous; LCM=lacosamide; 
min=minutes; PK=pharmacokinetics; T=time
a Noninvasive BP (systolic and diastolic) and pulse rate will be measured after at least 3 minutes at rest, when 
feasible, at the indicated approximate time points before and after the start of each iv LCM infusion.
b A 12-lead ECG will be performed at the indicated approximate time points before and after the start of each iv 
LCM infusion. Care should be taken to assure proper lead placement and quality ECG recordings. Subjects should 
be at rest at least 5 minutes prior to each ECG recording and should be motionless during the recording, when 
feasible.
c Samples for PK will be drawn after ECG and vital signs have been taken. Plasma samples will be obtained from 
the opposite arm in which the solution for infusion was administered for the first iv LCM infusion (Day 1) and the 
final iv LCM infusion (Day 2 to 5/Early Termination), predose and postdose, at the time points indicated in the 
table. Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in the 
event of a relevant treatment-emergent AE. Depending on the target duration defined for the cohort and subject 
tolerability, end of infusion can be at 15, 30, or 60 minutes, or whenever the infusion is stopped (if prematurely 
terminated).
d Time points are in reference to T0 (start of infusion) except the postdose PK sample, which should be obtained 
within 1 to 4 hours after the end of the iv LCM infusion.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 153 of 240
Has been changed to:
Table 5-2:
Timing of infusion, blood sampling, and measurement of vital signs 
and ECG on Treatment Days (Infusion Day 1 to Day 5)
Approximate time points in relation 
to iv LCM infusion  
Vital signsa
12-lead ECGb
PK blood samplingc
-59min to -3min
Xd
-20min (±10 min)
X
-10min (±5 min)
X
T0 (start of infusion)
+5min (±2 min)
X
+10min (±2 min)
X
+15min (±5 min)
X
+20min (±5 min)
X
+30min (±5 min)
X
+45min (±5 min)
X
+60min (±10 min)
X
X
+1h to +4he
X
+2h (±15 min)
X
X
AE=adverse event; BP=blood pressure; ECG=electrocardiogram; h=hours; iv=intravenous; LCM=lacosamide; 
min=minutes; PK=pharmacokinetics; T=time
a Noninvasive BP (systolic and diastolic) and pulse rate will be measured after at least 3 minutes at rest, when 
feasible, at the indicated approximate time points before and after the start of each iv LCM infusion.
b A 12-lead ECG will be performed at the indicated approximate time points before and after the start of each iv 
LCM infusion. Care should be taken to assure proper lead placement and quality ECG recordings. Subjects should 
be at rest (sitting or supine) at least 3 minutes prior to each ECG recording and should be motionless during the 
recording, when feasible.
c If the postdose PK sample is taken at a similar time for ECG and vital signs (ie, the 2 hour time point), the PK 
sample will be drawn after ECG and vital signs have been taken. Plasma samples will be obtained a different 
region of the body from the region in which the solution for infusion was administered for the first iv LCM 
infusion (Day 1). If the subject has more than 1 iv LCM infusion, it is optional to also collect plasma samples for 
the final iv LCM infusion (Day 2 to 5/Early Termination), predose and postdose, at the time points indicated in the 
table. Additional blood samples for PK analysis can be taken at the discretion of the investigator, especially in the 
event of a relevant treatment-emergent AE. Depending on the target duration defined for the cohort and subject
tolerability, end of infusion can be at 15, 30, or 60 minutes, or whenever the infusion is stopped (if prematurely 
terminated).
d For the first LCM infusion, the predose PK sample is required for OLL and RxL subjects and not required for IIL 
subjects. For optional PK sample collection of a subsequent LCM infusion, the predose sample should be collected 
from all subjects.
e Time points are in reference to T0 (start of infusion) except the postdose PK sample, which should be obtained 
within 1 to 4 hours after the end of the iv LCM infusion.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 154 of 240
Change #22
Section 5.3 Rationale for study design and selection of dose, first 4 paragraphs
EP0060 is an open-label, multicenter study to investigate the safety and tolerability of iv LCM as 
replacement for oral LCM therapy in pediatric subjects with epilepsy aged ≥4 to <17 years. A 
separate Phase 2/3 study investigating the use of iv LCM as replacement for oral LCM therapy in 
pediatric subjects with epilepsy ≥1 month to <4 years of age is planned. The results of EP0060 
will provide safety and PK data regarding the use of the iv LCM formulation in pediatric subjects 
(≥4 to <17 years of age). The EP0060 design is based on the study design for SP757, which 
evaluated iv LCM replacement in adults with partial-onset seizures, as well as based on design 
elements of other pediatric iv AED studies.
The iv LCM formulation is approved at doses of 200 to 400mg/day as adjunctive therapy in the 
treatment of partial-onset seizures in subjects ≥16 years of age (depending on country-specific 
labeling) with epilepsy when oral administration is temporarily not feasible. 
A weight-based LCM dosing scheme for pediatric subjects is being evaluated in Phase 3 
double-blinded, placebo-controlled studies and targets similar LCM plasma concentrations as 
those observed in adults given 400mg/day. As such, the target doses of LCM for the Phase 3 
studies are 8 to 12mg/kg/day; however, subjects entering EP0060 can be on a wider range of 
LCM doses based on the ranges of doses allowed in the long-term, open-label studies (2 to 
12mg/kg/day or 100 to 600mg/day). Thus, the iv LCM doses being evaluated in EP0060 will 
range from 2 to 12mg/kg/day or 100 to 600mg/day for subjects enrolling from the long-term 
open-label studies and for subjects currently prescribed VIMPAT and enrolling directly into 
EP0060. 
EP0060 will initially enroll older pediatric subjects (Cohort 1), which will include at least 
20 subjects ≥12 to <17 years of age. Cohort 2 (at least 20 subjects ≥8 to <12 years of age) and 
Cohort 3 (at least 20 subjects ≥4 to <8 years of age) will follow sequentially based on DMC 
recommendation. After the first 10 subjects in each cohort have received iv LCM over infusion 
durations of 30 to 60 minutes, the enrollment will be temporarily put on hold for the DMC to
review the available safety and tolerability data. Based on their review, the DMC will 
recommend the target infusion duration for the remaining subjects in the cohort (ie, 30 to 
60 minutes or 15 to 30 minutes), if the study/cohort should be stopped, and if the next cohort can 
be initiated, and if a new iv LCM study in younger pediatric subjects (≥1 month to <4 years of 
age) can be initiated.
Have been changed to:
EP0060 is an open-label, multicenter study to investigate the safety and tolerability of iv LCM in 
pediatric subjects with epilepsy aged ≥4 to <17 years. A separate Phase 2/3 study investigating 
the use of iv LCM in pediatric subjects with epilepsy ≥1 month to <4 years of age is planned. 
The results of EP0060 will provide safety and PK data regarding the use of the iv LCM 
formulation in pediatric subjects (≥4 to <17 years of age). The EP0060 design is based on 
components of the study design for SP757, which evaluated iv LCM replacement in adults with 
partial-onset seizures, as well as based on design elements of other pediatric iv AED studies. In 
an effort to maximize the patient pool used in the evaluation of the safety of iv LCM in pediatric 
subjects, Protocol Amendment 2 has opened enrollment to also include OLL and RxL subjects 
who are on a stable dose of oral LCM and elect to receive iv LCM as well as IIL subjects who 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 155 of 240
are not currently taking LCM and initiate adjunctive LCM treatment using iv LCM. This 
expansion of the subject population occurred prior to the start of study enrollment. Protocol 
Amendment 2 has also included the option for RxL and IIL subjects to continue oral LCM 
treatment after completion of iv LCM, if determined clinically appropriate, in SP848. If required, 
a short-term supply of oral LCM solution will be provided for RxL and IIL subjects transitioning 
to start SP848 to ensure continuity of LCM treatment while allowing flexibility to schedule a 
clinical visit to initiate SP848. For RxL and IIL subjects who do not continue into SP848 (either 
by choice or not clinically appropriate), an additional telephone contact approximately 30 days 
after last dose of iv LCM IMP is added in order to collect final safety data. 
The iv LCM formulation is approved at doses of 200 to 400mg/day as adjunctive therapy in the 
treatment of partial-onset seizures in subjects ≥16 years of age (depending on country-specific 
labeling) with epilepsy when oral administration is temporarily not feasible, which can also
include initiation of LCM treatment. 
A weight-based LCM dosing scheme for pediatric subjects is being evaluated in Phase 3 
double-blinded, placebo-controlled studies and targets similar LCM plasma concentrations as 
those observed in adults given 400mg/day. As such, the target doses of LCM for the Phase 3 
studies are 8 to 12mg/kg/day; however, subjects entering EP0060 can be on a wider range of 
LCM doses based on the ranges of doses allowed in the long-term, open-label studies (2 to 
12mg/kg/day or 100 to 600mg/day). Thus, the iv LCM doses being evaluated in EP0060 will 
range from 2 to 12mg/kg/day or 100 to 600mg/day for OLL and RxL subjects, with a maximum 
dose of 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, this range of doses 
above also includes the pediatric starting dose of 2mg/kg/day (subjects <50kg) or 100mg/day 
(subjects ≥50kg), which is the same as those used in the Phase 3 pediatric LCM studies. The 
LCM dose at initiation of treatment should remain constant for at least 7 days prior to a LCM 
dose increase.
EP0060 will initially enroll at least 40 older pediatric subjects (Cohort 1) and will include at least 
20 subjects ≥12 to <17 years of age and at least 20 subjects ≥8 to <12 years of age. Cohort 2 (at 
least 20 subjects ≥4 to <8 years of age) will follow sequentially based on DMC recommendation. 
After the first 20 subjects (Cohort 1) or 10 subjects (Cohort 2) have received iv LCM over 
infusion durations of 30 to 60 minutes, the DMC will review the available safety and tolerability 
data. Based on their review, the DMC will recommend the target infusion duration for the 
remaining subjects in the cohort (ie, 30 to 60 minutes for all remaining subjects or 15 to 30 
minutes [only for subjects who would directly benefit from an increased infusion rate, in the 
opinion of the Investigator; otherwise 30 to 60 minutes]), if the study/cohort should be stopped, 
and if the next cohort can be initiated, and if a new iv LCM study in younger pediatric subjects 
(≥1 month to <4 years of age) can be initiated (Section 12.7.2).
Change #23
Section 6.1 Inclusion criteria 
To be eligible to participate in EP0060, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject or by the parent(s) or legal 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 156 of 240
representative. The Informed Consent form or a specific Assent form, where required, will be 
signed and dated by minors.
2. Subject/legal representative is considered reliable and capable of adhering to the protocol, 
visit schedule, and medication intake according to the judgment of the investigator.
3. Subject is male or female from ≥4 to <17 years of age. 
4. Subject has, in the opinion of the investigator, adequate seizure control for participation in 
EP0060, and is able to comply with all study requirements including admission to the health 
care facility, multiple blood draws, and iv infusions. Subject (or parent[s] or legal 
representative) is willing to comply with all study requirements.
5. Subject is participating in a long-term, open-label study with LCM or is currently prescribed 
oral VIMPAT and needs to undergo a procedure, is admitted to an EMU or health care 
facility, or other situations where iv administration of LCM is clinically appropriate.
6. Subject is an acceptable candidate for venipuncture and iv infusion.
Subjects who are participating in a long-term, open-label study with LCM must fulfill the 
following additional inclusion criteria:
7. Subject is currently enrolled in a long-term, open-label study, receiving oral LCM for the 
treatment of epilepsy.
8. Subject has been on a stable bid dosage regimen of oral LCM for the last 3 days in their 
long-term, open-label study.
9. Subject is expected to benefit from participation in EP0060, in the opinion of the 
investigator.
Subjects who are currently prescribed oral VIMPAT and enroll directly into EP0060 must fulfill 
the following additional inclusion criteria:
10. Subject has been prescribed oral VIMPAT at a dose of 2mg/kg/day to 12mg/kg/day (for 
subjects <50kg) or 100mg/day to 600mg/day (for subjects ≥50kg). 
11. Subject has been prescribed oral VIMPAT for the treatment of epilepsy for at least 1 month 
prior to Screening and has not been prescribed or maintained on VIMPAT for the purposes of 
participating in EP0060. Prescribed oral VIMPAT dose must be stable for at least 7 days, and 
intake of the prescribed total daily dose confirmed for at least 3 days prior to first infusion.
12. If the subject is on a concomitant AED, the daily dosage regimen of AED therapy must be 
kept constant for a period of at least 1 week prior to Screening. VNS is allowed, but settings 
must be kept constant for a period of at least 1 week prior to Screening.
Has been changed to:
To be eligible to participate in EP0060, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject or by the parent(s) or legal 
representative. The Informed Consent form or a specific Assent form, where required, will be 
signed and dated by minors.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 157 of 240
2. Subject is male or female from ≥4 to <17 years of age.
3. Subject has a diagnosis of epilepsy with partial-onset seizures or primary generalized 
tonic-clonic seizures.
4. Subject meets 1 of the following criteria:
 OLL subject: Subject is currently receiving oral LCM as adjunctive or monotherapy as 
participants in an open-label long-term study (SP848, EP0034, or other pediatric study); 
OR,
 RxL subject: Subject is currently receiving prescribed oral LCM from commercial supply 
(eg, VIMPAT) as adjunctive or monotherapy; OR, 
 IIL subject: Subject is not currently receiving LCM and will receive iv LCM as 
adjunctive treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL 
subjects.
5. Subject is an OLL or RxL subject and meets both of the following criteria: 
 Subject has been administered LCM for the treatment of epilepsy for at least 2 weeks 
prior to Screening; AND, 
 Subject has been administered (OLL) or prescribed (RxL) oral LCM at a dose of 
2mg/kg/day to 12mg/kg/day (for subjects <50kg) or 100mg/day to 600mg/day (for 
subjects ≥50kg). Open-label study drug LCM (OLL) or prescribed oral LCM dose (RxL) 
must be stable for at least 3 days prior to first LCM infusion.
-OR-
Subject is an ILL subject and is on a stable dosage regimen of at least 1 AED. The daily 
dosage regimen of concomitant AED therapy must be kept constant for a period of at least 2 
weeks prior to Screening.
6. Subject is an acceptable candidate for venipuncture and iv infusion.
7. Subject is, in the opinion of the investigator, able to comply with all study requirements. 
Subject (or parent[s] or legal representative) is willing to comply with all study requirements.
Change #24
Section 6.2 Exclusion criteria
Subjects are not permitted to enroll in EP0060 if any of the following criteria are met:
1. Subject has previously received iv LCM in this study. 
2. Subject has any medical, neurological, or psychiatric condition that, in the opinion of the 
investigator, could jeopardize the subject’s health or compromise the subject’s ability to 
participate in EP0060.
3. Subject has clinically significant hypotension or bradycardia.
4. Subject ≥6 years of age has a lifetime history of suicide attempt (including an actual attempt, 
interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 158 of 240
indicated by positive responses (“Yes”) to either Question 4 or Question 5 of the C-SSRS at 
Screening.
5. Subject does not have a diagnosis of epilepsy.
6. Subject is taking monoamine oxidase inhibitors (MAOIs).
Subjects who are participating in a long-term, open-label study with LCM are not permitted to 
enroll in EP0060 if any of the following additional criteria are met:
7. Subject has any ongoing AE in their long-term, open-label study that, in the opinion of the 
investigator, could jeopardize or would compromise the subject’s ability to participate 
EP0060.
Subjects who are currently prescribed oral VIMPAT are not permitted to directly enroll in 
EP0060 if any of the following additional criteria are met:
8. Subject has a medical condition that could reasonably be expected to interfere with drug 
distribution, metabolism, or excretion.
9. Subject has a known hypersensitivity to any component of the investigational medicinal 
product (IMP).
10. Subject is a female of childbearing potential and does not practice an acceptable method of 
contraception for the duration of participation in EP0060. 
a) Medically acceptable contraceptive method includes oral or depot contraceptive 
treatment with at least 30μg ethinylestradiol per intake (or 50μg if associated with 
carbamazepine [or other strong enzyme inducers, eg, phenobarbital, primidone, 
oxcarbazepine]) which must be used in conjunction with a barrier method. Sexual 
abstinence is also an acceptable method of contraception. 
b) 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. Females of childbearing potential must have a negative pregnancy test at the 
Screening Visit.
11. Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total 
bilirubin level greater than or equal to 2 times the upper limit of normal (ULN), or creatinine 
clearance less than 30mL/min.
12. Subject has a clinically relevant ECG abnormality, in the opinion of the principal investigator 
(ie, second or third degree heart block at rest or a QT prolongation greater than 450ms).
13. Subject has hemodynamically significant heart disease (eg, heart failure).
14. Subject has an arrhythmic heart condition requiring medical therapy.
15. Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias.
16. Subject has only nonepileptic events, including psychogenic seizures, which could be 
confused with seizures. If both epileptic and nonepileptic events are present, epileptic events 
must be distinguished from nonepileptic phenomena.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 159 of 240
17. Subject has been treated with felbamate for at least 12 months prior to entering EP0060 and 
has experienced any toxicity issues with this treatment. Note: Any subject who is currently 
treated with felbamate, and has received felbamate for a period of less than 12 months, is 
excluded from EP0060. 
18. Subject has an acute or subacutely progressive central nervous system disease. Subject has 
epilepsy secondary to a progressing cerebral disease or any other progressive or 
neurodegenerative disease (malignant brain tumor or Rasmussen syndrome).
19. Subject has a known cardiac sodium channelopathy, such as Brugada syndrome.
Has been changed to:
Subjects are not permitted to enroll in EP0060 if any of the following criteria are met:
1. Subject has previously received iv LCM in this study. 
2. Subject has any medical, neurological, or psychiatric condition that, in the opinion of the 
investigator, could jeopardize the subject’s health or compromise the subject’s ability to 
participate in EP0060.
3. Subject has clinically significant hypotension or bradycardia in the opinion of the 
investigator.
4. Subject ≥6 years of age has a lifetime history of suicide attempt (including an actual attempt, 
interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as 
indicated by positive responses (“Yes”) to either Question 4 or Question 5 of the C-SSRS at 
Screening.
5. Subject is taking monoamine oxidase A inhibitors (MAOI-A). 
For OLL subjects, enrollment in EP0060 is not permitted if any of the following additional 
criteria are met:
6. Subject has any ongoing AE in their long-term, open-label study that, in the opinion of the 
investigator, could jeopardize or would compromise the subject’s ability to participate 
EP0060 or the subject meets any of the criteria for required withdrawal from the long-term 
open-label study.
For RxL and IIL subjects, enrollment in EP0060 is not permitted if any of the following 
additional criteria are met:
7. Subject has a medical condition that could reasonably be expected to interfere with drug 
absorption, distribution, metabolism, or excretion.
8. Subject has a known hypersensitivity to any component of the investigational medicinal 
product (IMP).
9. Subject is a female of childbearing potential and does not practice an acceptable method of 
contraception for the duration of participation in EP0060. 
a) Medically acceptable contraceptive method includes oral or depot contraceptive 
treatment with at least 30μg ethinylestradiol per intake (or 50μg if associated with 
carbamazepine [or other strong enzyme inducers, eg, phenobarbital, primidone, 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 160 of 240
oxcarbazepine]) which must be used in conjunction with a barrier method. Sexual 
abstinence is also an acceptable method of contraception. 
b) 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. Females of childbearing potential must have a negative pregnancy test at the 
Screening Visit.
10. Subject has creatinine clearance less than 30mL/min.
11. Subject has a clinically relevant ECG abnormality, in the opinion of the principal investigator 
(ie, second or third degree heart block at rest or a QT prolongation greater than 450ms).
12. Subject has hemodynamically significant heart disease (eg, heart failure).
13. Subject has an arrhythmic heart condition requiring medical therapy.
14. Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias.
15. Subject has an acute or subacutely progressive central nervous system disease. Subject has 
epilepsy secondary to a progressing cerebral disease or any other progressive or 
neurodegenerative disease (malignant brain tumor or Rasmussen syndrome).
16. Subject has a known cardiac sodium channelopathy, such as Brugada syndrome.
17. Lacosamide is intended for treatment of generalized convulsive status epilepticus. 
18. Subject has exclusively typical absence (Type IIA1) or atypical absence (Type IIA2) seizures 
(no other generalized seizure types are reported).
19. Subject has diagnosis of Dravet’s syndrome.
20. Subject has >2 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). 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 Case Report form (CRF).
If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at screening, 
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.
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation. This includes re-screening.
For IIL subjects, enrollment in EP0060 is not permitted if the following additional criterion 
is met:
21. Subject has been treated with LCM within the last 3 months prior to Screening.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 161 of 240
Change #25
Section 6.1 Withdrawal criteria
Subjects are free to withdraw from EP0060 at any time, without prejudice to their continued 
care.
Subjects must be withdrawn from EP0060 if any of the following events occur:
1. Subject experiences intolerable AEs and AEs associated with iv administration that, in the 
opinion of the investigator, preclude further participation in EP0060.
2. The subject requires more than 5 days of iv LCM dosing.
3. The sponsor or a regulatory agency requests withdrawal of the subject.
4. Subject has corrected QT interval (QTc) ≥500ms that is confirmed by a cardiologist over 
read on any ECG.
5. Subject becomes pregnant during the study, as evidenced by a positive serum or urine 
pregnancy test.
6. Subject develops a second- or third-degree atrioventricular (AV) block or another clinically 
relevant change in medical condition (or ECG) as determined by the investigator, or if the 
investigator feels it is in the interest of the subject to withdraw.
7. For subjects ≥6 years of age, subject has actual suicidal ideation since last visit as indicated 
by a positive response (“Yes”) to either Question 4 or Question 5 of the “Children’s Since 
Last Visit” version of C-SSRS. The subject should be referred immediately to a Mental 
Healthcare Professional and must be withdrawn from EP0060.
8. Subject is unwilling or unable to continue, or the parent/legal guardian is unwilling or unable 
to allow the subject to continue in EP0060.
9. Investigator decides that withdrawal from further participation would be in the subject’s best 
interest.
10. In the case of liver function test (LFT) results of transaminases (AST, ALT, or both) 
≥3x ULN to <5xULN and total bilirubin ≥2xULN or transaminases (AST, ALT, or both) 
≥5xULN, the study medication 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.
Participation in EP0060 may be discontinued for any of the following reasons:
11. Subject experiences convulsive status epilepticus.
12. Subject has any clinically relevant change in medical or psychiatric condition (if, in the 
opinion of the investigator, the change in condition warrants discontinuation from EP0060).
13. Subject requires a medication that is not permitted by the protocol (see Section 7.8.1).
14. Subject and/or delegated caregiver is noncompliant with EP0060 procedures or medication, 
in the opinion of the investigator.
15. Transaminases (AST, ALT, or both) ≥3xULN to <5xULN, in the presence of normal total 
bilirubin, will be repeated within a few days. If the repeat testing confirms the abnormality 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 162 of 240
(ie, transaminases are ≥3xULN to <5xULN with normal bilirubin), then weekly monitoring 
of LFTs should continue until resolved (ie, <3xULN or stable condition). The investigator is 
to decide whether or not to stop the study medication.
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject in advance.
Investigators should also attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. Withdrawal assessments will be recorded in EP0060. For subjects returning to a 
long-term, open-label study, withdrawal assessments from the long-term open-label study should 
be evaluated separately from the EP0060 withdrawal assessments. For subjects considered as lost 
to follow up, the investigator should make efforts (at least 1 phone call and 1 written message to 
the subject), and document his/her efforts (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 Case Report form (CRF) must 
document the primary reason for withdrawal or discontinuation.
Has been changed to:
Subjects are free to withdraw from EP0060 at any time, without prejudice to their continued 
care. The following criteria for subject withdrawal from EP0060 are outlined below. Additional 
discontinuation criteria for potential drug-induced liver injury are presented in Section 6.3.1.
Subjects must be withdrawn from EP0060 if any of the following events occur:
1. Subject experiences intolerable AEs and AEs associated with iv administration that, in the 
opinion of the investigator, preclude further participation in EP0060.
2. The subject requires more than 10 iv LCM doses.
3. The sponsor or a regulatory agency requests withdrawal of the subject.
4. Subject has corrected QT interval (QTc) ≥500ms that is confirmed by a cardiologist over 
read on any ECG.
5. Subject becomes pregnant during the study, as evidenced by a positive urine pregnancy test.
6. Subject develops a second- or third-degree atrioventricular (AV) block or another clinically 
relevant change in medical condition (or ECG) as determined by the investigator, or if the 
investigator feels it is in the interest of the subject to withdraw.
7. For subjects ≥6 years of age, subject has actual suicidal ideation since last visit as indicated 
by a positive response (“Yes”) to either Question 4 or Question 5 of the “Children’s Since 
Last Visit” version of C-SSRS. The subject should be referred immediately to a Mental 
Healthcare Professional and must be withdrawn from EP0060.
8. Subject is unwilling or unable to continue, or the parent/legal guardian is unwilling or unable 
to allow the subject to continue in EP0060.
9. Investigator decides that withdrawal from further participation would be in the subject’s best 
interest.
Participation in EP0060 may be withdrawn for any of the following reasons:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 163 of 240
10. Subject experiences generalized convulsive status epilepticus.
11. Subject has any clinically relevant change in medical or psychiatric condition (if, in the 
opinion of the investigator, the change in condition warrants discontinuation from EP0060).
12. Subject requires a medication that is not permitted by the protocol (see Section 7.8.1).
13. Subject and/or delegated caregiver is noncompliant with EP0060 procedures or medication, 
in the opinion of the investigator.
14. Subject who initiated adjunctive LCM treatment in EP0060 and requires a change in LCM 
dose during the Treatment Period.
15. Subject electively administering LCM requires more than 2 iv doses. If, in the opinion of the 
Investigator, there is a clinical need to administer more than 2 iv doses, the subject may 
remain in the study. The Investigator should document the clinical need in the medical 
record/source documents. 
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject in advance. Investigators should also attempt to obtain information on subjects in the 
case of withdrawal. Withdrawal assessments, which are the same as those for Final Visit, will be 
recorded in EP0060. For subjects considered as lost to follow up, the investigator should make 
efforts (at least 1 phone call and 1 written message to the subject/subject’s parent or legal 
guardian), and document his/her efforts (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 Case Report form (CRF) must 
document the primary reason for withdrawal.
For subjects returning to a long-term, open-label study, withdrawal assessments from the 
long-term open-label study should be evaluated separately from the EP0060 withdrawal 
assessments. The Medical Monitor may provide guidance on whether the subject should return to 
continued treatment within the long-term open-label study (OLL subject), be allowed to enroll in 
SP848 (RxL and IIL subjects), or withdraw completely. For the particular withdrawal criterion of 
requiring more than 10 iv doses or if the route of LCM administration (iv) is the sole reason for 
withdrawal of consent, subjects may be allowed to return to their long-term open-label study 
(OLL subjects) or enroll in SP848 (RxL and IIL subjects) after discussion with and agreement 
from the Medical Monitor. If an OLL subject is advised to withdraw from the long-term 
open-label study (EP0034 or SP848), the subject will be required to return to the long-term 
open-label study to complete the required withdrawal and safety follow-up assessments.
Change #26
Section 6.3.1 Potential drug-induced liver injury IMP discontinuation criteria
Has been added:
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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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 164 of 240
The PDILI criteria below require immediate and permanent discontinuation of IMP: 
x 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:
x Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right 
upper quadrant pain or tenderness. Hypersensitivity symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, >5%).
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
investigator. 
x 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 10.6.2. 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 CRF must document the primary 
reason for IMP discontinuation.
Change #27
Section 7.1 Description of investigational medicinal product
Investigational medicinal product will be provided as LCM solution in glass iv vials (10mg/mL 
in a 20mL vial; each vial contains LCM 200mg). Both the iv vials and the carton containing the 
vials will be labeled for the study.
Has been changed to:
7.1.1
Lacosamide solution for infusion
Investigational medicinal product for infusion will be provided as LCM solution for infusion in 
glass iv vials (10mg/mL in a 20mL vial; each vial contains LCM 200mg). Both the iv vials and 
the carton containing the vials will be labeled for the study.
Further details regarding dilution and storage of LCM solution for infusion are provided in the 
IMP Handling Manual.
7.1.2
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 165 of 240
Lacosamide syrup/oral solution will be provided in a polyethylene terephthalate bottle 
(10mg/mL in 200mL bottle). The bottle will be labeled for the study. Study medication will be 
measured and administered via a dosing syringe.
Lacosamide oral solution will only be distributed to those RxL and IIL subjects who are eligible 
and choose to participate in SP848. This supply, if required, will be dispensed at Visit 2 in the 
event that additional time is needed to coordinate scheduling of Visit 1 of SP848, and any 
remaining oral LCM solution will be returned to the site at the Transition Visit.
Change #28
Section 7.2 Treatment(s) to be administered
Treatment Period (up to 5 days)
During the Treatment Period, iv LCM will be administered bid at approximately 12-hour 
intervals, once in the morning and once in the evening, for up to 5 days. The iv LCM dose will 
be equivalent (mg-for-mg) to the subject’s current stable oral LCM dose or prescribed oral 
VIMPAT dose (always in bid regimen) of 2 to 12mg/kg/day or 100 to 600mg/day. The first 
iv LCM dose will be given on Day 1.
A calibrated infusion pump should be used for delivering the iv LCM dose at a constant rate over 
the target duration defined for the cohort. A previously unused vial must be administered for 
each dose. Dilution is not required prior to administration of iv LCM. If needed to obtain a total 
volume compatible with the specified infusion duration, the iv LCM solution can be diluted; iv 
LCM is compatible with the following diluents: dextrose 5%, lactated ringers, and normal saline 
(NaCl 0.9%). The total volume of diluent should be calculated not to exceed a total volume of 
fluid intake/day based on the Holliday-Segar equation as follows: 
x For children weighing ≤10kg: 100mL/kg body weight
x For children weighing >10 to ≤20kg: 1000mL + 50mL/kg for each kg body weight ≥10kg
x For children weighing ≥20kg: 1500mL + 20mL/kg for each kg body weight ≥20kg
Intravenous LCM administration should be completed within 4 hours after dilution.
For the first 10 subjects ≥12 to <17 years of age enrolled into Cohort 1, iv LCM should be 
infused over a duration of 30 minutes but no longer than 60 minutes whenever possible. 
The duration of infusion for the remaining subjects in Cohort 1 and subsequent cohort(s) will be 
based on DMC recommendation: 
x 30 minutes but no longer than 60 minutes whenever possible,
x OR 15 minutes but no longer than 30 minutes whenever possible.
Further details on the timing of DMC recommendations regarding infusion duration are provided 
in Section 12.7.2.
When necessary for the safety of the subject or when the investigator deems it appropriate, the 
iv LCM dose can be modified after the first infusion, once the Day 1 PK samples have been 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 166 of 240
A subject cannot receive iv LCM for more than 5 days in EP0060. If a subject requires iv LCM 
treatment for more than 5 days, the subject may continue on iv VIMPAT, but he/she will need to 
discontinue EP0060. Subjects who were enrolled in a long-term, open-label study may be 
eligible to resume participation in that study, according to the protocol requirements. If subjects 
need to discontinue LCM, the subjects should be tapered off LCM gradually as specified in their 
long-term, open-label study. This taper should occur as a part of the long-term, open-label study.
Subjects who were prescribed oral VIMPAT should continue AED treatment at the discretion of 
the treating physician. 
Has been changed to:
7.2.1
Treatment Period 
During the Treatment Period, subjects will receive at least 1 dose of iv LCM at the dose levels 
noted below. The first iv LCM dose will be given on Day 1. If more than 1 infusion is given, iv 
LCM will be administered bid at approximately 12-hour intervals, once in the morning and once 
in the evening, for up to 10 doses (or up to 5 days) for clinical need administration or up to 2 
consecutive doses (over approximately 24 hours) for elective administration. 
Specific dosing regimens for subjects who will receive iv LCM replacement therapy for oral 
treatment (OLL and RxL subjects) or for subjects who will initiate adjunctive LCM treatment 
(IIL subjects) are as follows:
x Replacement for oral treatment: For OLL and RxL subjects, the iv LCM daily dose 
will be equivalent (mg-for-mg) to the subject’s current oral LCM dose or prescribed oral 
LCM (ie, VIMPAT) dose (always in bid regimen) of 2 to 12mg/kg/day or 100 to 
600mg/day. The first infusion must be equivalent to the subject’s stable oral LCM dose.
x Adjunctive LCM treatment initiation: For IIL subjects, the iv LCM daily dose will be 
2mg/kg/day for subjects <50kg or 100mg/day for subjects ≥50kg. As LCM is given bid, 
the actual dose for the first infusion will be LCM 1mg/kg (subjects weighing <50kg) or 
50mg (subjects weighing ≥50kg). For these subjects, the LCM dose should remain 
unchanged for the duration of the iv Treatment Period (see Section 6.3).
A calibrated infusion pump should be used for delivering the iv LCM dose at a constant rate over 
the target duration defined for the cohort. A previously unused vial must be administered for 
each dose. Dilution is not required prior to administration of iv LCM. If needed to obtain a total 
volume compatible with the specified infusion duration, the iv LCM solution can be diluted; iv 
LCM is compatible with the following diluents: dextrose 5%, lactated ringers, and normal saline 
(NaCl 0.9%). The total volume of diluent should be calculated not to exceed a total volume of 
fluid intake/day based on the Holliday-Segar equation as follows: 
x For children weighing ≤10kg: 100mL/kg body weight
x For children weighing >10 to ≤20kg: 1000mL + 50mL/kg for each kg body weight ≥10kg
x For children weighing ≥20kg: 1500mL + 20mL/kg for each kg body weight ≥20kg
Intravenous LCM administration should be completed within 4 hours after dilution.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 167 of 240
For the first 20 subjects ≥8 to <17 years of age enrolled into Cohort 1 and the first 10 subjects ≥4 
to <8 years in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no longer 
than 60 minutes whenever possible. 
The duration of infusion for the remaining subjects in each cohort will be based on DMC 
recommendation: 
x EITHER target infusion duration of 15 minutes but no longer than 30 minutes only in 
subjects who would directly benefit from an increased infusion rate, in the opinion of the 
Investigator. Subjects who will not directly benefit from a 15 to 30 minute infusion, in the
opinion of the Investigator, cannot receive the faster infusion. These subjects should receive 
an infusion of 30 minutes but no longer than 60 minutes.
x OR all remaining subjects will have a target infusion duration of 30 minutes but no longer 
than 60 minutes
Further details on the timing of DMC recommendations regarding infusion duration are provided 
in Section 12.7.2.
For OLL and RxL subjects, the iv LCM dose can be modified after the first infusion when 
necessary for the safety of the subject or when the investigator deems it appropriate; however, 
modification should not occur until after the Day 1 PK samples have been taken. Modification of 
iv LCM dose is not permitted for IIL subjects.
A subject cannot receive iv LCM for more than 10 doses (up to 5 days) within the Treatment 
Period of EP0060 (or more than 2 consecutive doses [over approximately 24 hours] for elective 
administration. If a subject requires iv LCM treatment for more than 5 days, the subject may 
continue on iv VIMPAT, but he/she will need to discontinue EP0060. Upon 
completion/discontinuation of EP0060, OLL subjects are eligible to resume participation in their 
respective open-label study, according to the protocol requirements. If a subject is withdrawn 
from EP0060 due to requirement of more than 10 iv LCM doses, the subject may be allowed to 
return to their long term open-label study (OLL subjects) or enroll in SP848 (RxL and IIL 
subjects) after discussion with and agreement from the Medical Monitor. If an OLL subject 
meets any other “must withdrawal” criteria for the respective open-label study, the subject will 
return to the open-label study to complete the appropriate withdrawal assessments and safety 
follow-up.
For RxL and IIL subjects, AED treatment will continue at the discretion of the treating 
physician, upon completion/discontinuation of EP0060. If determined clinically appropriate, 
these subjects will be given the option to continue oral LCM treatment for up to 2 years in 
SP848. If LCM treatment is not continued in SP848 (either by choice or not clinically 
appropriate), RxL and IIL subjects will be followed for approximately 30 days after the Final 
Visit in order to collect safety data. All concomitant medications taken during this 30-day period, 
including prescribed AEDs, will be collected at TC2.
If subjects need to discontinue LCM, the subjects should be tapered off LCM either as specified 
in their long-term, open-label study or at the discretion of the treating physician for RxL and IIL 
subjects. For OLL subjects this taper should occur as a part of the long-term, open-label study 
and not as a part of EP0060.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 168 of 240
Change #29
Section 7.2.2 Transition oral lacosamide
Oral LCM solution will only be distributed to those RxL and IIL subjects who are eligible and 
choose to participate in SP848.
For OLL and RxL subjects, the oral LCM daily dose will be equivalent (mg-for-mg) to the 
subject’s current oral LCM dose or prescribed oral LCM (ie, VIMPAT) dose (always in bid 
regimen) of 2 to 12mg/kg/day.
For IIL subjects, the oral LCM solution daily dose (always in bid) will be 2mg/kg/day for 
subjects <50kg or 100mg/day for subjects ≥50kg if the subject has been taking LCM for less than 
7 days. If the subject has reached 7 days of LCM exposure, an increase in dose titration can be 
initiated.
Has been added
Change #30
Section 7.5 Handling and storage requirements
The investigator (or designee) is responsible for the safe and proper storage of LCM at the site. 
Lacosamide stored by the investigator is to be kept in a secured area with limited access.
Lacosamide is to be stored according to instructions on the label. Appropriate storage conditions 
must be ensured either by controlled room temperature and 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) before further use of LCM.
The CPM (or designee) will transmit the out-of-range temperature (copy of the temperature log 
and duration of the out-of-range temperature, if available) 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 use of LCM.
Has been changed to:
The investigator (or designee) is responsible for the safe and proper storage of LCM at the site. 
Lacosamide 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 by controlling the temperature and by 
completion of a temperature log in accordance with local requirements on a regular basis, 
showing minimum and maximum temperatures reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual.
In the case of dispensing oral LCM solution, the investigator (or designee) will instruct the 
subject’s parent or guardian to store the IMP following the instructions on the label.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 169 of 240
Changes #31 and #32
Section 7.6 Drug accountability, first and last paragraphs
First paragraph:
A Drug Accountability form will be used to record LCM dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any LCM 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.
Last paragraph:
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers) and unused LCM containers must be reconciled and 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.
Have been changed to:
First paragraph:
A Drug Accountability form will be used to record LCM dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any LCM lost, damaged (due to breakage or wastage), not used, partially 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.
Last paragraph:
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers)/partially used, unused, damaged, and/or expired LCM must be reconciled and either 
destroyed at the site according to local laws, regulations, and UCB SOPs or returned to UCB (or 
designee). Investigational medicinal product intended for the study cannot be used for any other 
purpose than that described in this protocol.
Change #33
Section 7.8.1 Permitted and prohibited concomitant treatments (medications and 
therapies), first and second paragraphs
Stable use of amphetamines and sedative antihistamines is permitted during the study. 
Use of MAOIs is prohibited during EP0060.
Have been changed to:
Stable use of amphetamines and sedative antihistamines is permitted during the study. 
Use of the following concomitant treatments (medications and therapies) is prohibited during 
EP0060:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 170 of 240
x MAOI-A inhibitors
x Cannabidiols not approved or indicated for epilepsy by local health authority
Change #34
Section 7.10 Randomization and numbering of subjects
Subjects will not be randomized in EP0060. For a subject enrolled in a long-term, open-label 
study, the unique identification number assigned to them in that study will be used to identify 
them and maintain subject confidentiality throughout EP0060. Direct-enroll subjects prescribed 
VIMPAT will be assigned a unique identification number in EP0060.
Has been changed to:
Subjects will not be randomized in EP0060. For an OLL subject, the unique identification 
number assigned to them in that study will be used to identify them and maintain subject 
confidentiality throughout EP0060. A unique identification number in EP0060 will be assigned 
for RxL and IIL subjects.
Change #35
Section 8.1.1 Visit 1a and Visit 1b (Day -7 to Day -1) Screening and/or Baseline, first 
2 paragraphs
8.1.1
Visit 1a and Visit 1b (Day -7 to Day -1) Screening and/or Baseline 
Prior to the conduct of any study-related procedures, a complete explanation (both verbally and 
written) of the nature and purpose of the study will be given to the subject (when possible or as 
required according to local IRBs/IECs) and the subject’s parent/legal guardian by the 
investigator (or designee). The subject’s parent/legal guardian will be requested to sign and date 
the IRB/IEC-approved Informed Consent form. When possible, or as required by the local 
IRB/IEC, an IRB/IEC-approved written Assent form will also be properly executed and 
documented. During the Screening Period, subjects will be evaluated for their suitability for 
enrollment. The Screening Period assessments may be conducted on more than 1 day and begin 
up to 7 days prior to Day 1 (Visit 1a). When necessary for the well-being of the subject or when 
the investigator deems it appropriate, the Screening and/or Baseline Visit can occur on the same 
day as the first iv LCM infusion (Day 1) provided all test results are available and reviewed to 
assess inclusion and exclusion criteria prior to enrollment/treatment in the study. Oral LCM will 
be administered in accordance with each subject’s current stable LCM dosage regimen of 2 to 
12mg/kg/day or 100 to 600mg/day. For subjects enrolled in a long-term open-label study, the 
oral LCM will be taken from the long-term open-label study supply. For subjects who have been 
prescribed VIMPAT, oral LCM will be taken from the subject’s prescribed VIMPAT supply.
Each subject’s eligibility for the study will be determined on the basis of the inclusion/exclusion 
criteria at Visit 1a and/or Visit 1b. The following pretreatment assessments will be carried out at 
Visit 1a:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 171 of 240
Have been changed to:
8.1.1
Visit 1a and Visit 1b (Day -7 to Day 1) Screening and/or Baseline 
Prior to the conduct of any study-related procedures, a complete explanation (both verbally and 
written) of the nature and purpose of the study will be given to the subject (when possible or as 
required according to local IRBs/IECs) and the subject’s parent/legal guardian by the 
investigator (or designee). The subject’s parent/legal guardian will be requested to sign and date 
the IRB/IEC-approved Informed Consent form. When possible, or as required by the local 
IRB/IEC, an IRB/IEC-approved written Assent form will also be properly executed and 
documented. During the Screening Period, subjects will be evaluated for their suitability for 
enrollment. The Screening Period assessments may be conducted on more than 1 day and begin 
up to 7 days prior to Day 1 (Visit 2). 
The Screening and/or Baseline Visit can occur on the same day as the first iv LCM infusion 
(Day 1), if necessary, provided all test results (ie, 12-lead ECG and laboratory results) are 
available and reviewed to assess inclusion and exclusion criteria prior to enrollment/treatment in 
the study. For all subjects, laboratory results obtained for routine diagnostic and medical care can 
be used whenever possible if collected no more than 24 hours prior to Screening/Baseline Visit 
in order to minimize blood loss associated with the study. At the Screening/Baseline Visit, the 
use of a central or local laboratory is at the discretion of the investigator.
If Screening/Baseline do not occur on the same day as the first infusion, oral LCM will be 
administered for OLL and RxL subjects during the Screening/Baseline Period from their 
open-label study or prescribed LCM supply in accordance with each subject’s current stable 
LCM dosage regimen of 2 to 12mg/kg/day or 100 to 600mg/day. For IIL subjects, no LCM will 
be administered during the Screening Period.
Each subject’s eligibility for the study will be determined on the basis of the inclusion/exclusion 
criteria at Visit 1a and/or Visit 1b. Demographic data will be collected at Visit 1a. The following 
pretreatment assessments will be carried out at Visit 1a:
Change #36
Section 8.1.1 Visit 1a and Visit 1b (Day -7 to Day -1) Screening and/or Baseline, bullets 6, 7, 
8, 9, 10, 15, 16, 20, and 21
x Medical history update for subjects from long-term open-label studies, or complete medical 
history for subjects receiving prescribed VIMPAT
x Lacosamide dosing history (including formulation, date, and time of use, and dose and unit 
during the last 3 days)
x Prior and concomitant medication(s) assessment (prior medications will only be collected for 
direct-enroll subjects; concomitant medications from the long-term open-label studies will be 
followed, as well as the recording of new concomitant medications during EP0060 for all 
enrolled subjects)
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 172 of 240
x Pregnancy testing for subjects of childbearing potential will be serum testing at the Screening 
Visit for subjects who are prescribed VIMPAT and urine testing for subjects enrolled in 
long-term, open-label studies
x Vital signs (BP and pulse rate) assessment
x 12-lead ECG 
x Oral LCM administration
x C-SSRS (for subjects ≥6 years of age)
Have been changed to:
x Medical history update for OLL subjects from long-term open-label studies, or complete 
medical history for RxL and IIL subjects 
x For OLL and RxL subjects, LCM dosing history (including formulation, date, and time of 
use, and dose and unit during the last 3 days)
x Prior and concomitant medication(s) assessment (prior medications will only be collected for 
direct-enroll subjects)
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose),  
VNS settings, and/or use of ketogenic diet
x Urine pregnancy testing for subjects of childbearing potential 
x Vital signs (BP and pulse rate) assessment (measured on subjects who have rested [sitting or 
supine] for at least 3 minutes, when feasible)
x 12-lead ECG (conducted on subjects who have rested [sitting or supine] at least 3 minutes 
prior to each ECG recording, when feasible)
x C-SSRS (for subjects ≥6 years of age). For subjects <6 years, signs and symptoms of 
depression will be evaluated as described in Section 10.7.5.
If Screening/Baseline and the first infusion do not occur on the same day, oral LCM 
administration for OLL and RxL subjects will continue in accordance with each subject’s LCM 
dosage regimen and using the subject’s open-label study or prescribed oral LCM supply, 
respectively.
And
x Seizure history for RxL and IIL subjects
Has been added
Change #37
Section 8.1.1 Visit 1a and Visit 1b (Day -7 to Day -1) Screening and/or Baseline, bullets 18 
and 19
x ILAE (International League against Epilepsy) seizure classification
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 173 of 240
x Admission to the unit
Have been deleted
Change #38
Section 8.1.1 Visit 1a and Visit 1b (Day -7 to Day 1) Screening and/or Baseline, Visit 1b 
bullets 2, 4, 6, 8, 9, 11, and 12
x Lacosamide dosing history (including formulation, date, and time of use, and dose and unit 
during the last 3 days)
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
x Blood sample for clinical chemistry and hematology 
x Vital signs (BP and pulse rate) assessment
x 12-lead ECG
x Oral LCM administration
x C-SSRS (for subjects ≥6 years of age)
Have been changed to:
x For OLL and RxL subjects, the LCM dosing history will be collected (including formulation, 
date, and time of use, and dose and unit during the last 3 days)
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose), 
VNS settings, and/or ketogenic diet
x Blood sample for clinical chemistry and hematology (Repetition of laboratory assessments is 
at the discretion of the investigator if Visit 1b is on a separate day from Visit 1a.)
x Vital signs (BP and pulse rate) assessment (measured on subjects who have rested [sitting or 
supine] for at least 3 minutes, when feasible)
x 12-lead ECG (conducted on subjects who have rested [sitting or supine] at least 3 minutes 
prior to each ECG recording, when feasible)
x C-SSRS (for subjects ≥6 years of age). For subjects <6 years, signs and symptoms of 
depression will be evaluated as described in Section 10.7.5.
If Screening/Baseline and the first infusion do not occur on the same day, oral LCM 
administration for OLL and RxL subjects will continue in accordance with each subject’s LCM 
dosage regimen and using the subject’s open-label study or prescribed oral LCM supply, 
respectively.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 174 of 240
Change #39
Section 8.1.1 Visit 1a and Visit 1b (Day -7 to Day -1) Screening and/or Baseline, Visit 1b 
bullet 10
x Admission to the unit
Has been deleted
Change #40
Section 8.1.1 Visit 1a and Visit 1b (Day -7 to Day -1) Screening and/or Baseline, Visit 1b, 
new bullets (currently numbering) 11, 12, 13, 14, and 15
x Medical procedures
x Medical history update for OLL subjects, or complete medical history for RxL and IIL 
subjects
x Urine pregnancy testing for subjects of childbearing potential
x Brief physical examination
x Brief neurological examination
Have been added
Change #41
Section 8.2.1 Visit 2 (Day1), first paragraph
Intravenous LCM infusion treatment will begin at this visit, and iv LCM will be administered bid 
at approximately 12-hour intervals, once in the morning and once in the evening, for up to 
5 days. Screening laboratory assessments may be conducted up to and including the day of the 
infusion provided they are reviewed and meet inclusion/exclusion criteria prior to the infusion. 
The following assessments will be carried out:
Has been changed to:
Intravenous LCM infusion treatment will begin at this visit. Subjects will receive at least 1 dose 
of iv LCM. If more than 1 infusion is given, iv LCM will be administered bid at approximately 
12-hour intervals, once in the morning and once in the evening, for up to 10 doses (or up to 5 
days) for clinical need administration or up to 2 consecutive doses (over approximately 24 hours) 
for elective administration. 
Screening laboratory assessments may be conducted up to and including the day of the infusion 
provided they are reviewed and meet inclusion/exclusion criteria prior to the infusion. 
Section 8.1.1 details under what conditions laboratory results within 24 hours of signing the 
Informed Consent form can be used. 
The following assessments will be carried out:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 175 of 240
Change #42
Section 8.2.1 Visit 2 (Day 1), bullets 2, 4, 7, 8, 9 and 10 for first infusion
x Medical procedures and medical history update
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or VNS settings
x 12-lead ECG (approximately 20 minutes prior to iv LCM infusion and at approximately 15, 
30, 60 minutes, and 2 hours from the start of iv LCM infusion)
x Vital signs of BP and pulse rate (approximately 10 minutes prior to iv LCM infusion and at 
approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of iv LCM infusion)
x Blood sample for LCM PK (Blood draws will be performed on the arm opposite the arm 
where the iv LCM infusion will be administered at the time points described in Section 9).
An indwelling cannula used for the iv LCM infusion may not be used for PK blood 
sampling.) 
x C-SSRS (for subjects ≥6 years of age)
Have been changed to:
x Medical procedures
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose), 
VNS settings, and/or use of ketogenic diet
x 12-lead ECG (approximately 20 minutes prior to iv LCM infusion and at approximately 15, 
30, 60 minutes, and 2 hours from the start of iv LCM infusion) (conducted on subjects who 
have rested [sitting or supine] for at least 3 minutes prior to each ECG recording, when 
feasible)
x Vital signs of BP and pulse rate (approximately 10 minutes prior to iv LCM infusion and at 
approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of iv LCM infusion) 
(measured on subjects who have rested [sitting or supine] for at least 3 minutes, when 
feasible)
x Blood sample for LCM PK (Blood draws will be performed from a region of the body that is 
different from the region where the iv LCM infusion will be administered at the time points 
described in Section 9. An indwelling peripheral cannula used for the iv LCM infusion may 
not be used for PK blood sampling.) 
x C-SSRS (for subjects ≥6 years of age) after infusion. For subjects <6 years, signs and 
symptoms of depression will be evaluated as described in Section 10.7.5.
Change #43
Section 8.2.1 Visit 2 (Day 1), bullets 11, 12, and 13
x Brief physical examination
x Brief neurological examination
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 176 of 240
x For RxL and IIL subjects who are eligible and choose to participate in the long-term open 
label oral LCM study SP848 after completion of EP0060, a short-term oral LCM solution 
will be dispensed at Visit 2. This supply is to allow continuity of LCM treatment after the last 
iv LCM infusion and the scheduled Transition Visit.
Have been added
Change #44
Section 8.2.1 Visit 2 (Day 1), second paragraph
The second iv LCM infusion will be administered at approximately 12 hours after the start of the 
first infusion, and the following assessments will be carried out:
Has been changed to:
If a second iv LCM infusion is given, it will be administered at approximately 12 hours after the 
start of the first infusion, and the following assessments will be carried out:
Change #45
Section 8.2.1 Visit 2 (Day 1), bullets 3 and 4 for second infusion
x 12-lead ECG (approximately 20 minutes prior to iv LCM infusion and at approximately 15, 
30, 60 minutes, and 2 hours from the start of iv LCM infusion)
x Vital signs of BP and pulse rate (approximately 10 minutes prior to iv LCM infusion and at 
approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of iv LCM infusion)
Have been changed to:
x 12-lead ECG (approximately 20 minutes prior to iv LCM infusion and at approximately 15, 
30, 60 minutes, and 2 hours from the start of iv LCM infusion) (conducted on subjects who 
have rested [sitting or supine] for at least 3 minutes prior to each ECG recording, when 
feasible)
x Vital signs of BP and pulse rate (approximately 10 minutes prior to iv LCM infusion and at 
approximately 5, 10, 20, 45, 60 minutes, and 2 hours from the start of iv LCM infusion) 
(measured on subjects who have rested [sitting or supine] for at least 3 minutes, when 
feasible)
Change #46
Section 8.2.1 Visit 2 (Day 1), bullets 6 and 7 for second infusion
x Concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose), 
VNS settings, and/or use of ketogenic diet
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 177 of 240
Have been added
Change #47
Section 8.2.1 Visit 2 (Day 1), last paragraph
If the subject has more than 1 iv LCM infusion, it is optional to also collect blood samples for 
LCM PK before and after the final iv LCM infusion at the time points described in Section 9. In 
addition, during the course of the study, additional blood samples for PK analysis can be taken at 
the discretion of the investigator, especially in the event of a relevant treatment-emergent AE.
Has been added
Change #48
Section 8.2.2 Visit 3 (Day 2 to Day 5)
If iv LCM treatment is continued after Day 1, assessments for Visit 3 must be completed each 
day of iv LCM treatment in EP0060. Assessments for Visit 3 (Day 2 to 5) are the same as those 
described for Visit 2 (Day 1) in Section 8.2. Blood samples for LCM PK will be obtained before 
and after the final iv LCM infusion at the time points described in Section 9. In addition, during 
the course of the study, additional blood samples for PK analysis can be taken at the discretion of 
the investigator, especially in the event of a relevant treatment-emergent AE. 
Has been changed to:
If iv LCM treatment is continued after Day 1, assessments for Visit 3 must be completed each 
day of iv LCM treatment in EP0060. Assessments for Visit 3 (Day 2 to 5) are the same as those 
described for Visit 2 (Day 1) in Section 8.2. If the subject has more than 1 iv LCM infusion, it is 
optional to also collect blood samples for LCM PK before and after the final iv LCM infusion at 
the time points described in Section 9. In addition, during the course of the study, additional 
blood samples for PK analysis can be taken at the discretion of the investigator, especially in the 
event of a relevant treatment-emergent AE.
Change #49
Section 8.3 Unscheduled Visit, bullets 1, 3, 6, and 9
x Medical procedures and medical history update
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose) 
and/or VNS settings
x BP and pulse rate
x C-SSRS (for subjects ≥6 years of age). The C-SSRS assessment should be completed if the 
Unscheduled Visit is due to an AE.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 178 of 240
Has been changed to:
x Medical procedures
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose), 
VNS settings, and/or use of ketogenic diet
x BP and pulse rate (measured on subjects who have rested [sitting or supine] for at least 
3 minutes, when feasible)
x C-SSRS (for subjects ≥6 years of age). The C-SSRS assessment should be completed if the 
Unscheduled Visit is due to an AE. For subjects <6 years, signs and symptoms of depression 
will be evaluated as described in Section 10.7.5.
Change #50
Section 8.3 Unscheduled Visit, bullets 5 and 7
x 12-lead ECG
x Blood sample for LCM PK (Blood draws will be performed on the arm opposite the arm 
where the iv LCM infusion will be administered. An indwelling cannula used for the iv LCM 
infusion may not be used for PK blood sampling)
Has been deleted
Change #51
Section 8.3 Unscheduled Visit, bullets 10 and 11
x Brief physical examination
x Brief neurological examination
Have been added
Change #52
Section 8.3 Unscheduled Visit, final paragraph
Additional assessments can be performed at the investigator’s discretion, including collection of 
a blood sample for LCM PK if the reason for the unscheduled visit is an AE.
Has been added
Change #53
Section 8.4.1 Final Visit (Day 2 to 6 [now Day 1 to 6])/Termination Visit, first paragraph
The following assessments will be carried out the day after the last dose of iv LCM for subjects 
who complete the study, discontinue the study, or withdraw from the study prematurely:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 179 of 240
Has been changed to:
If the last iv infusion of LCM for the study occurs in the morning, the Final Visit may occur on 
the same day as the last infusion, time permitting. Otherwise, the Final Visit should occur on the 
following day (ie, last infusion in evening).
The following assessments will be carried out after the last dose of iv LCM for subjects who 
complete the study, discontinue the study, or withdraw from the study prematurely:
Change #54
Section 8.4.1 Final Visit (Day 2 to 6 [now Day 1 to Day 6])/Termination Visit, bullets 1, 3, 4, 
8, 9, 10, 12, and 13
x Medical procedures and medical history update
x Pregnancy testing for subjects of childbearing potential
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose) 
and/or VNS settings
x Blood sample for clinical chemistry and hematology
x 12-lead ECG
x BP and pulse rate
x Oral LCM administration
x C-SSRS (for subjects ≥6 years of age) 
Have been changed to:
x Medical procedures
x Urine pregnancy testing for subjects of childbearing potential 
x Concomitant AED(s) assessment (identification of drugs, amount and time of last dose), 
VNS settings, and/or use of ketogenic diet
x Blood sample for clinical chemistry and hematology which must be analyzed at the central 
laboratory
x 12-lead ECG (conducted on subjects who have rested [sitting or supine] for at least 3 minutes 
prior to each ECG recording, when feasible)
x BP and pulse rate (measured on subjects who have rested [sitting or supine] for at least 
3 minutes, when feasible)
x Oral LCM administration, if applicable:
 For OLL subjects, oral LCM administration will continue in accordance with each 
subject’s LCM dosage regimen using the subject’s open-label study LCM supply
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 180 of 240
 For RxL subjects who are not eligible or do not wish to continue LCM treatment in 
SP848, oral LCM administration may continue from the subject’s prescribed LCM supply 
at the physician’s recommended dosage regimen.
 For RxL and IIL subjects who are eligible and wish to enroll in SP848, oral LCM 
administration may continue from the short-term oral LCM solution that was dispensed at 
Visit 2. Additional assessments will be conducted at the Transition Visit, as outlined in 
Section 8.4.3.
x C-SSRS (for subjects ≥6 years of age) For subjects <6 years, signs and symptoms of 
depression will be evaluated as described in Section 10.7.5.
Change #55
Section 8.4.1 Final Visit (Day 2 to 6)/Termination Visit, last bullet
x Discharge from the unit
Has been deleted
Change #56
Section 8.4.2 Telephone Contact (Day 2 to Day 9), section title
Has been changed to:
Section 8.4.2 Telephone Contact 1 (Day 2 to Day 9)
 
Change #57
Section 8.4.2 Telephone Contact (Day 2 to Day 9), first paragraph
One or 2 days after the Final Visit, a safety follow-up/telephone assessment will be conducted 
during the End-of-Study Period (2 to 9 days after Visit 2/Day 1). The following assessments will 
be collected:
Has been changed to:
One to 3 days after the Final Visit, a safety follow-up/telephone assessment will be conducted 
during the End-of-Study Period. The following assessments will be collected:
Change #58
Section 8.4.2 Telephone Contact (Day 2 to Day 9), first and last bullets
x Medical procedures and medical history update
x Oral LCM administration
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 181 of 240
Have been changed to:
x Medical procedures
x Information regarding LCM dosing since Final Visit
Change #59
Section 8.4.2 Telephone Contact (Day 2 to Day 9), new bullet
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
Has been added
Change #60
Section 8.4.3 Transition Visit (Day 1 to Day 13)
For RxL and IIL subjects who are eligible and wish to enroll in SP848, the Final Visit and 
Transition Visit may occur on the same day or may occur up to 7 days after the Final Visit. The 
Transition Visit for EP0060 should occur on the same day as Visit 1 in SP848.
The following assessments will be conducted at the Transition Visit if the visit is not conducted 
on the same day as the Final Visit:
x Collection of the short-term oral LCM solution, if dispensed at Visit 2 
x Information regarding LCM dosing since Final Visit
x Concomitant medication(s) assessment
x AE reporting
Additional assessments for enrollment in SP848 (Visit 1) are detailed within the SP848 protocol.
Has been added
Change #61
Section 8.4.4 Telephone Contact 2 (Day 29 to Day 37)
Thirty days (±2 days) after the Final Visit, a safety follow-up/telephone assessment will be 
conducted during the End-of-Study Period (29 to 37 days after Visit 2/Day 1). This assessment 
will only occur for those subjects who directly enrolled in EP0060 and will not be continuing 
LCM therapy in SP848. 
The following assessments will be collected:
x Concomitant medication(s) assessment
x Concomitant AED(s) assessment (identification of drugs, amount, and time of last dose) 
and/or use of ketogenic diet
x AE reporting
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 182 of 240
x Information regarding LCM dosing since Telephone Contact 1
x Medical procedures
During the contact, the site should inquire as to whether the subject noted any change at the site 
of the infusion.
Has been added
Change #62
Section 9 ASSESSMENT OF PHARMACOKINETICS, first, second, third, and fourth 
paragraphs and first bullet point
Blood samples for the determination of LCM and SPM 12809 concentrations will be collected 
according to the tabular schedules of study procedures (see Section 5.2). In each case, the time 
the subject received the most recent dose of study medication and the time of blood sampling 
must be recorded.
During the Treatment Period, plasma samples will be taken for LCM and SPM 12809 
determination after ECG and vital signs have been taken. Plasma samples will be obtained from 
the opposite arm in which the solution for infusion was administered, at the following time 
points:
First iv LCM infusion (Day 1):
x Predose (within 1 hour prior to iv LCM dose)
Final iv LCM infusion (Day 2 to 5/Early Termination):
Have been changed to:
Blood samples for the determination of LCM and SPM 12809 concentrations will be collected 
according to the tabular schedules of study procedures (see Section 5.2). In each case, the time 
the subject received the most recent dose of IMP and the time of blood sampling must be 
recorded.
During the Treatment Period, plasma samples will be taken for LCM and SPM 12809 
determination after ECG and vital signs have been taken. Plasma samples will be obtained from 
a different region of the body from the region in which the solution for infusion was 
administered, at the following time points: 
First iv LCM infusion (Day 1) – required samples:
x Predose (within 1 hour prior to iv LCM dose) for OLL and RxL subjects
Final iv LCM infusion (Day 2 to 5/Early Termination) – optional samples:
Change #63
Section 10.1.6 Pregnancy, second bullet
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 183 of 240
x A Safety Follow Up Visit should be scheduled 1 to 2 days after the subject has discontinued 
her iv LCM infusion.
Has been changed to:
x A Safety Follow-Up Visit should be scheduled 1 to 3 days after the subject has discontinued 
her iv LCM infusion.
Change #64
Section 10.1.7 Suspected transmission of an infectious agent via a medicinal product
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE; such cases must be reported immediately, recorded in 
the AE module of the CRF, and followed as any other SAE. Any organism, virus, or infectious 
particle (eg, prion protein transmitting transmissible spongiform encephalopathy), pathogenic or 
nonpathogenic, is considered an infectious agent.
Has been added
Change #65
Section 10.1.8 (previously Section 10.1.7) 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 CRF. 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).
Has been changed to:
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the CRF. 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).
Change #66
Numbering for Section 10.1.8 (Safety signal detection) is now Section 10.1.9
Change #67
Section 10.2.1 Definition of serious adverse event, Bullet 5
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 184 of 240
x 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.)
Has been changed to:
x 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, but are not limited to, potential Hy’s Law [see 
Section 10.3], 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.)
Change #68
Section 10.2.3 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 Drug 
Safety database without limitation of time.
Has been changed to:
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. This 
follow-up requirement applies to AEs, SAEs, and AEs of special interest; further details 
regarding follow up of PDILI events are provided in Section 10.6.2.
Information on SAEs obtained after clinical database lock will be captured through the Patient 
Safety database without limitation of time.
Change #69
Section 10.3 Adverse events of special interest, last bullet point
x 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.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 185 of 240
Has been added
Change #70
Section 10.5 Anticipated serious adverse events, first paragraph
The following list of anticipated SAEs has been identified, as these events are anticipated to 
occur in the epilepsy population at some frequency that is independent of drug exposure. This 
original list will remain in effect for the duration of the protocol.
Has been changed to:
The following list of anticipated SAEs is anticipated to occur in the epilepsy population at some 
frequency that is independent of drug exposure. 
Change #71
Section 10.6 Laboratory measurements, first paragraph
Blood specimens for routine assay of hematology and clinical chemistry testing will be collected 
according to the tabular schedule of study assessments (Section 5.2). Samples will be prepared 
and evaluated by the local laboratory as described in the laboratory manual.
Has been changed to:
Blood specimens for routine assay of hematology and clinical chemistry testing will be collected 
according to the tabular schedule of study assessments (Section 5.2). To minimize risk from 
blood loss associated with this study, local laboratory results obtained for routine diagnostic and 
medical care can be used whenever possible if collected no more than 24 hours prior to 
Screening/Baseline Visit. Use of the central or local laboratory is at the discretion of the 
investigator for all visits except the Final Visit. The central laboratory must be used for 
laboratory samples collected at the Final Visit. Samples will be prepared and evaluated by a 
central laboratory as described in the laboratory manual.
Change #72
Section 10.6.1 Liver function tests (now Section 10.6.2)
Transaminases (AST, ALT, or both) ≥3xULN but <5xULN, in the presence of total bilirubin 
≥2xULN, or transaminases (AST, ALT, or both) ≥5xULN will result in immediate 
discontinuation of LCM and withdrawal of the subject from the study. The LFTs will be repeated 
as soon as possible, and in no case more than 1 week later.
Transaminases (AST, ALT, or both) ≥3xULN to <5xULN, in the presence of normal total 
bilirubin, will be repeated within a few days. If the repeat testing confirms the abnormality (ie, 
transaminases are ≥3xULN to <5xULN with normal bilirubin), then weekly monitoring of LFTs 
should continue until resolved (ie, <3xULN or stable condition). The investigator is to decide 
whether or not to stop the study medication. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 186 of 240
In all cases of transaminases (AST, ALT, or both) ≥3xULN, testing for hepatitis A, B, and C will 
be done.
Referral to a specialist (ie, hepatologist or gastroenterologist) is at the discretion of the 
investigator. This is recommended especially if the transaminase abnormalities >3xULN persist 
after discontinuation of the study medication.
Has been deleted (see Change #73).
Change #73
Numbering for Section 10.6.2 (Pregnancy testing) is now Section 10.6.1.
Change #74
Section 10.6.2 Liver function tests and evaluation of PDILI
The PDILI IMP discontinuation criteria for this study are provided in Section 10.6.2.2 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 10.3), and, if applicable, also reported as an 
SAE (see Section 10.2.1). 
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in 
Table 10‒3 (specific tests dependent on laboratory results and corresponding symptoms) and 
consultation with a local hepatologist (if applicable; discussed in Section 10.6.2.1). 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 10.6.2.4).
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 CRF 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.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 187 of 240
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. 
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. 
REDACTED COPY 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 188 of 240
Table 10-3: Required investigations and follow-up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptoms
a of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULN
b
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 10.6.2.3);
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
≥5xULN
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 10.6.2.2).
Not required 
unless otherwise 
medically 
indicated (at 
discretion of 
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 10.6.2.3).
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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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 189 of 240
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 10.6.2.1. 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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30 Apr 2018
Clinical Study Protocol
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EP0060
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Page 190 of 240
10.6.2.1
Consultation with 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 Section 10.6.2.3) and SAE report (if applicable).
10.6.2.2
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 10‒3 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.
10.6.2.3
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 10‒4 (laboratory measurements) and Table 10‒5 (additional information). Results of the 
laboratory measurements and information collected are to be submitted to the sponsor on the 
corresponding CRF. 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:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 191 of 240
Table 10-4: 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
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:
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30 Apr 2018
Clinical Study Protocol
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EP0060
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Page 192 of 240
Table 10-5: 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:
x 
History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty 
liver disease”)
x 
Adverse reactions to drugs
x 
Allergies
x 
Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1 antitrypsin 
deficiency)
x 
Recent travel 
x 
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
10.6.2.4
Follow-up evaluation
Potential drug-induced liver injury events require follow-up monitoring as described in 
Table 10‒3. 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.
Has been added
Change #75
Section 10.7.2 12-lead ECG, second paragraph
Care should be taken to assure proper lead placement and quality ECG recordings. Subjects 
should rest at least 5 minutes prior to each recording and should be motionless during the 
recording, when feasible.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 193 of 240
Has been changed to:
Care should be taken to assure proper lead placement and quality ECG recordings. Subjects 
should rest at least 3 minutes prior to each recording and should be motionless during the 
recording, when feasible.
Change #76
Section 10.7.4 Complete physical examination (now Physical examination)
The complete physical examination will include cardiac and respiratory function via 
auscultation, and review of all body systems. Clinically significant physical examination findings 
are to be reported as AEs.
Has been changed to:
10.7.4.1
Complete physical examination
The complete physical examination will include cardiac and respiratory function via 
auscultation, and review of all body systems. Clinically significant physical examination findings 
are to be reported as AEs.
10.7.4.2
Brief physical examination
The brief physical examination will includes a review of the following body systems: 
cardiovascular, pulmonary, abdominal (hepato-gastrointestinal), and dermatologic.
Change #77
Section 10.7.5 Assessment of suicidality, first paragraph
Suicidality will be assessed by trained study personnel using the C-SSRS (Columbia University 
Medical Center, 2008). For subjects ≥6 years of age, this scale will be used for screening as well 
as to assess suicidal ideation and behavior that may occur during the study. The C-SSRS will be 
completed according to the tabular schedule of study procedures (Table 5-1). All subjects who 
are ≥6 years of age will complete the “Baseline/Screening” version of the C-SSRS at Visit 1 and 
will complete the “Since Last Visit” version at subsequent visits. If a subject becomes 6 years of 
age during the study, the "Already Enrolled" version of the C-SSRS should be used at the first 
visit at which the subject is 6 years of age and the “Since Last Visit” version used at subsequent 
visits.
Has been changed to:
Suicidality will be assessed by trained study personnel using the C-SSRS (Columbia University 
Medical Center, 2008). For subjects ≥6 years of age, this scale will be used for screening as well 
as to assess suicidal ideation and behavior that may occur during the study. The C-SSRS will be 
completed according to the tabular schedule of study procedures (Table 5‒1). If the Screening 
and Baseline visit is on the same day, the C-SSRS does not need to be completed twice. The 
C-SSRS should be performed once per day during the Treatment Period. If Screening/Baseline 
and Visit 2 occur on the same day, 2 assessments should be completed with 1 predose and 1 after 
infusion.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 194 of 240
All subjects who are ≥6 years of age will complete the “Baseline/Screening” version of the 
C-SSRS at Visit 1 and will complete the “Since Last Visit” version at subsequent visits. If a 
subject becomes 6 years of age during the study, the "Already Enrolled" version of the C-SSRS 
should be used at the first visit at which the subject is 6 years of age and the “Since Last Visit” 
version used at subsequent visits.
Change #78
Section 10.7.6 Complete neurological examination (now Neurological examination)
The complete neurological examination will include selected assessment of general neurological 
status (level of consciousness, mental status, speech), cranial nerves, reflexes, motor system 
(general motor status, muscle strength, muscle tone), coordination/cerebellar function, and 
sensation. Clinically significant neurological examination findings are to be reported as AEs.
Has been changed to:
10.7.6.1
Complete neurological examination
The complete neurological examination will include selected assessment of general neurological 
status (level of consciousness, mental status, speech), cranial nerves, reflexes, motor system 
(general motor status, muscle strength, muscle tone), coordination/cerebellar function, and 
sensation. Clinically significant neurological examination findings are to be reported as AEs.
10.7.6.2
Brief neurological examination
The brief neurological examination will include selected assessment of mental status, cranial 
nerves, and coordination/cerebellar function.
Changes #79 to #80
Section 11.3.1 Case Report form completion, first and third paragraphs
First paragraph:
The study is performed using remote data capture (RDC); the investigator is responsible for 
prompt reporting of accurate, complete, and legible data in the electronic CRFs and in all 
required reports.
Third paragraph:
Corrections made after the investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the investigator.
Have been changed to:
First paragraph:
The study is performed using electronic data capture (EDC); the investigator is responsible for 
prompt reporting of accurate, complete, and legible data in the electronic CRFs and in all 
required reports.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 195 of 240
Third paragraph:
Corrections made after the investigator’s review and approval (by means of a 
password/electronic signature) will need to be reapproved by the investigator.
Change #81
Section 11.3.2 Database entry and reconciliation, first paragraph
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. As the study is performed using RDC, the data are entered into the electronic CRFs 
once and are subsequently verified.
Has been changed to:
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. As the study is performed using EDC, the data are entered into the electronic CRFs 
once and are subsequently verified.
Change #82
Section 12 STATISTICS, first paragraph
Selected disposition, exposure, demographic, and Baseline summaries will be presented by 
cohort and infusion duration, cohorts overall, and all subjects overall. Descriptive statistics will 
be displayed to provide an overview of the Baseline characteristics, PK, and safety results.
Has been changed to:
Selected disposition, exposure, demographic, and Baseline summaries will be presented by 
cohort and infusion duration, cohorts overall, and all subjects overall. Within cohort and infusion 
duration, presentation will include the IIL subject group and the OLL and RXL subject group.
Change #83
Section 12.1 Definition of analysis sets, first paragraph
The Safety Set (SS) will include subjects who received at least 1 dose of iv LCM. The SS will be 
the primary analysis set for the analysis of safety data.
Has been changed to:
The Safety Set iv (SS-iv) will include subjects who received at least 1 dose of iv LCM. The SS 
will be the primary analysis set for the analysis of safety data.
The Safety Set (SS) will include subjects who received at least 1 dose of LCM (oral or iv). 
Selected safety summaries will be presented for the SS.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 196 of 240
Change #84
Section 12.3 Planned pharmacokinetic analyses
Descriptive statistics for LCM and SPM 12809 plasma concentrations, including but not limited 
to geometric mean and CV, will be computed for pre-infusion and post-infusion time points on 
each infusion day where LCM and SPM 12809 plasma are collected.
Has been changed to:
Descriptive statistics for LCM and SPM 12809 plasma concentrations, including but not limited 
to geometric mean and CV, will be computed for pre-infusion and post-infusion time points on 
each infusion day where LCM and SPM 12809 plasma are collected. Data will be presented by 
cohort and infusion duration, and the IIL and OLL and RXL groups of subjects in EP0060 will 
also be presented.
Change #85
Section 12.4 Planned safety and other analyses (now titled Planned safety analyses), first 
paragraph
Safety analyses will be presented by cohort and infusion duration, cohorts overall, and all 
subjects overall. Within cohort and infusion duration, the OLL and RxL groups of subjects and 
the IIL subject group will also be presented.
Has been added
Change #86
Section 12.5 Handling of protocol deviations 
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct, or on the primary safety outcomes (if applicable) for an 
individual subject. The criteria for identifying important protocol deviations will be defined 
within the appropriate protocol-specific document. Important protocol deviations will be 
reviewed as part of the ongoing data cleaning process and data evaluation. All important 
deviations will be identified and documented prior to database lock to confirm exclusion from 
analysis sets.
Has been changed to:
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on the primary safety outcomes for an individual subject. The criteria for 
identifying important protocol deviations will be defined within the appropriate protocol-specific 
document. Important protocol deviations will be reviewed as part of the ongoing data cleaning 
process and data evaluation. All important deviations will be identified and documented prior to 
database lock to confirm exclusion from analysis sets.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 197 of 240
Change #87
Section 12.7 Planned interim analysis and data monitoring
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of the first 10 subjects in each cohort. 
Has been changed to:
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of the first 20 subjects in Cohort 1 and after completion of 
the first 10 subjects in Cohort 2. 
Change #88
Section 12.7.2 Data Monitoring Committee. Paragraph 2 through end of section
EP0060 will begin with Cohort 1, where at least 20 subjects ≥12 to <17 years of age will be 
enrolled to receive iv LCM. For the first 10 subjects in Cohort 1, iv LCM should be infused over 
a duration of 30 minutes but no longer than 60 minutes whenever possible. 
After completion of the first 10 subjects in Cohort 1, enrollment into Cohort 1 will be 
temporarily put on hold to allow for the DMC review of the safety and tolerability data from 
these subjects. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥8 to <12 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, enrollment into Cohort 2 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1 and Cohort 2. Based on this review, the DMC will make recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 2 should be stopped, 
x AND whether Cohort 3 can be initiated.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 198 of 240
For Cohort 3, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 3, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 3, enrollment into Cohort 3 will be 
temporarily put on hold for the DMC to review the available safety and tolerability data from 
Cohort 1, Cohort 2, and Cohort 3. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 3 with a target 
infusion duration of 15 minutes but no longer than 30 minutes whenever possible, 
x OR approximately 15 additional subjects will be enrolled in Cohort 3 with a target infusion 
duration of 30 minutes but no longer than 60 minutes whenever possible, 
x OR Cohort 3 should be stopped, 
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).
Has been changed to:
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion durations as follows:
 15 minutes but no longer than 30 minutes only in subjects who would directly benefit
from an increased infusion rate, in the opinion of the Investigator; OR,
 30 minutes but no longer than 60 minutes in subjects who would not directly benefit
from an increased infusion rate, in the opinion of the Investigator
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 199 of 240
After completion of the first 10 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion durations as follows: 
 15 minutes but no longer than 30 minutes only in subjects who would directly benefit
from an increased infusion rate, in the opinion of the Investigator; OR,
 30 minutes but no longer than 60 minutes in subjects who would not directly benefit
from an increased infusion rate, in the opinion of the Investigator
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 30 minutes but no longer than 60 minutes, 
x OR Cohort 2 should be stopped, 
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).
Change #89
Section 12.8 Determination of sample size
Approximately 75 subjects will be enrolled, which includes up to 3 cohorts of at least 
20 subjects. No formal sample size calculation has been performed. The sample size was deemed 
clinically appropriate for the evaluation of safety, tolerability, and PK of iv LCM administration 
in pediatric subjects with epilepsy.
Has been changed to:
Approximately 75 subjects will be enrolled, which includes up to 2 cohorts of at least 40 subjects 
for Cohort 1 and at least 20 subjects for Cohort 2. No formal sample size calculation has been 
performed. The sample size was deemed clinically appropriate for the evaluation of safety, 
tolerability, and PK of iv LCM administration in pediatric subjects with epilepsy. 
Changes #90 and #91
Section 15 References
Dichek B. Epilepsy: an ancient ailment that still eludes a cure. Scrip Magazine. 1999;Feb:9-11.
Has been deleted and 
Arkilo D, Gustafson M, Ritter FJ. Clinical experience of intravenous lacosamide in infants and 
young children. Eur J Paediatr Neurol. 2016;20(2):212-7.
CDC growth curves. Girls: http://www.cdc.gov/growthcharts/data/set1clinical/cj41c022.pdf. 
Boys: http://www.cdc.gov/growthcharts/data/set1clinical/cj41c021.pdf. 2000. 
REDACTED 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 200 of 240
Food and Drug Administration. Guidance for Industry. Drug-induced liver injury: premarketing 
clinical evaluation. US Dept of Health and Human Services, Center for Drug Evaluation and 
Research, Center for Biologics Evaluation and Research, 07/2009. 
Ngugi AK, Kariuki SM, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Incidence of 
epilepsy: A systematic review and meta-analysis. Neurology. 2011; 77(10): 1005–12.
Have been added
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 201 of 240
16.3
Protocol Amendment 3
Rationale for the amendment
The primary purpose of this substantial amendment is to lower the age of subjects from ≥4 years 
to ≥1 month in an effort to maximize the subject pool in the evaluation of iv LCM, to include age 
stratification within Cohort 2 to be most informative with regard to safety and PK, and to 
increase study enrollment from 75 to 100 subjects to reflect the inclusion of subjects down to 1 
month of age. Since initial conception of the study, substantial new safety and efficacy 
information on the lowest age group (≥1 month to <4 years of age) has been accumulated, 
reported, and published. The available safety information consists of postmarketing data (n=27 
patient cases), data from internal studies (n=15 patient cases), as well as from two published 
reports (n=15 and n=22 patient cases) (Arkilo et al, 2016; Welsh et al, 2017). These reports cover 
the age range from ≥1 month to <4 years of age and also cover the clinical spectrum from an 
open-label extension study with oral treatment to critically care patients receiving iv treatment. 
This data points to no specific risks in the age group after administration of Vimpat® and UCB, 
therefore, believes it is justified to open Cohort 2 to the lowest age group in agreement with the 
DMC outcome on safety of Cohort 1.
Additional changes include the following:
x Study contact information has been updated as applicable.
x Additional region to maximize enrollment has been included.
x Number of subjects included in the DMC process in Cohort 2 has been modified.
x The timing of the End-of-Study/Final Visit has been clarified.
x Wording regarding the taper of LCM for ILL subjects who discontinue use has been 
removed.
x US and EU regulatory authority approvals of LCM have been updated.
x Pharmacokinetic variables have been further defined as “Other”.
x Bicarbonate testing is optional for subjects weighing less than 8kg.
x New inclusion criterion has been added for all subjects.
x New exclusion criterion has been added for RxL and ILL subjects.
x Oral LCM should be administered approximately 12 hours after the final iv LCM infusion
has been clarified.
x PDILI language has been updated to most current UCB template.
x List of hematology PDILI laboratory measurements have been updated.
x List of chemistry PDILI laboratory measurements have been updated.
x Clarification has been added regarding the reading of 12-lead ECGs. 
x Definitions of analysis sets have been modified.
x Data presentations for planned pharmacokinetic and safety analyses have been revised.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 202 of 240
x Minor typographical errors and clarifications have been made and are not listed in the 
summary of changes.
Modifications and changes
Global changes
The following changes have been made throughout the protocol:
x Text has been modified to lower the age of subject enrollment to ≥1 month of age.
x Approximately 100 subjects will be included in EP0060.
x Asia with the possibility of other regions has been added to study regions.
x Age stratification has been included within Cohort 2. Every attempt will be made to enroll 20 
subjects ≥4 to <8 years of age, 12 subjects ≥2 to <4 years of age, and 12 subjects ≥1 month to 
<2 years of age.
x Number of subjects in the DMC process in Cohort 2 has been revised.
 For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to 
receive iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a 
duration of 30 minutes but no longer than 60 minutes whenever possible.
 After completion of the first 20 subjects in Cohort 2, the DMC will review the available 
safety and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC 
will make recommendations as follows: 
◦ 
EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with a 
target infusion duration of 15 minutes but no longer than 30 minutes only in subjects 
who would directly benefit from an increased infusion rate, in the opinion of the 
investigator. Subjects who will not directly benefit from a 15 to 30 minute infusion, in 
the opinion of the investigator, cannot receive the faster infusion. These subjects 
should receive an infusion of 30 minutes but no longer than 60 minutes. 
◦ 
OR approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 30 minutes but no longer than 60 minutes. 
◦ 
OR Cohort 2 should be stopped.
x The Final Visit can be conducted on the same day as the last dose of iv LCM if time permits 
to complete all assessments. Otherwise, the Final Visit should be conducted the day 
following the last dose of iv LCM.
x Text has been amended to include US and EU regulatory authority approvals of LCM for 
pediatric patients down to 4 years of age. 
 In the US, oral tablets and oral solution (syrup) of LCM are indicated for the treatment of 
partial-onset seizures in patients 4 years of age and older. As the safety of LCM injection 
for iv use has not been established in pediatric patients, LCM injection for iv use at 
infusion durations of 15 to 60 minutes is indicated for the treatment of partial-onset 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 203 of 240
seizures only in patients 17 years of age and older as an alternative when oral 
administration is temporarily not feasible. 
 Additionally, LCM has been approved in the EU (oral tablets, oral solution [syrup], and 
solution for iv infusion), as monotherapy and adjunctive therapy in the treatment of 
partial-onset seizures with or without secondary generalization in patients 4 years of age 
and older. The iv formulation at infusion durations of 15 to 60 minutes is approved as an 
alternative for patients when oral administration is temporarily not feasible.
x The Inclusion Criterion 8 has been added to enroll patients who weigh ≥4kg.
x The Exclusion Criterion 20a has been added to clarify RxL and IIL subject must not be 
currently participating in another study of IMP. 
x PDILI language has been modified with current UCB language to clarify which laboratory 
values IMP must be immediately and permanently discontinued.
x Text has been amended to clarify OLL subjects will not have a medical history performed in 
EP0060.
x The following changes were made to PDILI laboratory measurements:
 Hematocrit, hemoglobin, platelet count, RBC count, WBC count, and WBC differential 
count have replaced eosinophil count as hematology measurements. 
 ALT, AST, ALP, GGT, and albumin have been added to chemistry measurements.
x 12-lead ECG will be read by a central reader in addition to the initial review.
x Analyis sets have been defined as follows:
 The Safety Set (SS) will include subjects who received at least 1 dose of EP0060 study 
drug LCM (oral and/or iv). Selected safety summaries will be presented for the SS.
 The Safety Set iv (SS-iv) will include subjects in the SS who received at least 1 dose of 
EP0060 study drug iv LCM. The SS-iv will be the primary analysis set for the analysis of 
safety data.
 The Pharmacokinetic-Per Protocol Set (PK-PPS) will include all subjects in the SS-iv
having provided at least 1 measurable postdose plasma sample (with recorded sampling 
time) on at least 1 study day with documented iv LCM intake times and without 
important protocol deviations impacting the interpretability of the PK analysis.
Specific changes
Change #1
Title page
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY AND 
TOLERABILITY OF INTRAVENOUS LACOSAMIDE IN CHILDREN (≥4 TO <17 YEARS 
OF AGE) WITH EPILEPSY
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 204 of 240
Has been changed to:
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY AND
TOLERABILITY OF INTRAVENOUS LACOSAMIDE IN CHILDREN (≥1 MONTH TO <17 
YEARS OF AGE) WITH EPILEPSY
Change #2
STUDY CONTACT INFORMATION
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Has been changed to:
Sponsor Study Physician
Name:
 MD
Address:
UCB BIOSCIENCES, GmbH.
Alfred-Nobel-Straβe 10
40789 Monheim am Rhein
Germany
Phone:
Mobile:
Change #3
STUDY CONTACT INFORMATION
Clinical Project Manager
Name:
Address:
UCB BIOSCIENCES, Inc.
REDACTED 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 205 of 240
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Has been changed to:
Clinical Project Manager
Name:
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Not Applicable
Change #4
STUDY CONTACT INFORMATION
Clinical Trial Biostatistician
Name:
 MPH 
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709, USA
Phone:
Fax:
Has been changed to:
Clinical Trial Biostatistician
Name:
Address:
UCB BIOSCIENCES, GmbH.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 206 of 240
Alfred-Nobel-Straβe 10
40789 Monheim am Rhein
Germany
Phone:
Fax:
Not Applicable
Change #5
Section 1 SUMMARY
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of 
intravenous (iv) lacosamide (LCM; VIMPAT®) infusions in pediatric subjects ≥4 to <17 years of 
age with epilepsy. Investigation the use of iv LCM in pediatric subjects with epilepsy ≥1 month 
to <4 years of age is planned. 
EP0060 will include approximately 75 subjects. The following subjects will be eligible for 
enrollment in EP0060:
x Open-label LCM (OLL) subjects: currently receiving oral LCM as adjunctive or 
monotherapy as participants in an open-label long-term study (SP848, EP0034, or other 
pediatric study).
x Prescribed-LCM (RxL) subjects: currently receiving prescribed oral LCM from 
commercial supply (eg, VIMPAT) as adjunctive or monotherapy.
x Initiating iv LCM (IIL) subjects: not currently receiving LCM and will receive iv LCM as 
adjunctive treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL 
subjects.
Subjects can receive iv LCM as follows: 
x Replacement for oral LCM treatment (OLL and RxL subjects): 
 Clinical need administration: Subjects currently taking prescribed oral LCM (or any 
enteric LCM administration, eg, LCM administration by feeding tube) who need to 
undergo a procedure and are treated at an epilepsy monitoring unit (EMU) or health 
care facility, or other situations where iv administration is clinically appropriate and 
oral administration is not feasible (ie, surgery). In these subjects, the maximum 
number of iv doses of LCM is 10. 
 Elective administration: Subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) and elect to receive iv LCM 
administration at an EMU or healthcare facility. In these subjects, the maximum 
number of iv doses of LCM is 2.
x Adjunctive iv LCM treatment initiation (IIL subjects):
 Clinical need administration: Subjects not currently taking LCM who need to undergo 
a procedure, be treated at an EMU or health care facility, or other situations where iv 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 207 of 240
administration is clinically appropriate and oral administration is not feasible (ie, 
surgery). In these subjects, the maximum number of iv doses of LCM is 10.
 Elective administration: Subjects not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
Pediatric subjects entering into EP0060 from the OLL group will temporarily suspend their
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll into 
EP0060 from the RxL group will temporarily switch from their prescribed oral LCM treatment to 
the iv LCM formulation. Subjects in the IIL group will initiate adjunctive treatment with iv 
LCM. After completion of this study, eligible subjects from the RxL and IIL groups will have the 
option to continue LCM treatment in SP848. Subjects will be enrolled from approximately 40 
sites in North America and Europe. Additional sites or regions may be added if deemed 
necessary.
The primary objective of EP0060 is to evaluate the safety and tolerability of iv LCM infusion(s) 
in pediatric subjects ≥4 to <17 years with epilepsy. EP0060 is planned to include up to 
2 age-based cohorts with Cohort 1 including at least 40 subjects who are ≥8 to <17 years and 
Cohort 2 including at least 20 subjects who are ≥4 to <8 years. Within Cohort 1, at least 
20 subjects will be ≥12 to <17 years of age and at least 20 subjects will be ≥8 to <12 years of 
age. A Data Monitoring Committee (DMC) will review the safety and tolerability data for each 
cohort to make the following recommendations: the progression of the current cohort, including 
iv infusion durations to be evaluated, and progression to initiate enrollment in the next cohort 
(Cohort 2) or separate study for the evaluation of iv LCM in children <4 years of age (as detailed 
further below). 
EP0060 is comprised of the following study periods: 
x For all subjects:
 Screening and/or Baseline Period (up to 7 days),
 Treatment Period
(1) Clinical need administration: up to 10 doses or up to 5 days
(2) Elective administration: up to 2 consecutive doses over approximately 24 hours
 End-of-Study/Final Visit (1 day), 
 End-of-Study/Telephone Contact 1 (1 to 3 days),
x 
Additional visits or contacts as follows:
 RxL and IIL subjects who are eligible and choose to continue oral LCM treatment for 
up to 2 years in SP848
◦ 
Transition Visit, which can be concurrent with Final Visit or separate (up to 
7 days after Final Visit)
 RxL and IIL subjects who do not continue LCM treatment in SP848
◦ 
End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM). 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 208 of 240
For all subjects, the Screening, Baseline, Treatment Period, and Final Visit may occur in 1 day, 
provided the subject only requires 1 iv infusion, results of examinations (ie, 12-lead 
electrocardiogram [ECG], laboratory measurements) are available to allow verification of subject 
eligibility prior to infusion, and time permits for completion of Final Visit assessments. 
If further time is required for Screening assessments or to obtain results, the Screening Period 
can last up to 7 days. For OLL and RxL subjects, oral LCM will be administered during this time 
from their open-label study or prescribed LCM supply in accordance with each subject’s oral 
LCM dosage regimen. For IIL subjects, no LCM will be administered during the Screening 
Period.
During the Treatment Period, at least 1 dose of iv LCM will be administered. If more than 
1 infusion is given, infusions will occur twice daily (bid) at approximately 12-hour intervals for 
up to 10 doses (or up to 5 days for clinical need administration or up to 2 consecutive doses (over 
approximately 24 hours) for elective administration. For OLL and RxL subjects, the daily dose 
of iv LCM will be the same as the subject's current stable daily dose of oral LCM (2 to 
12mg/kg/day or 100 to 600mg/day). The maximum dose permitted in this study for OLL and 
RxL subjects is 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, the iv LCM 
dose will be 1mg/kg (subjects weighing <50kg) or 50mg (subjects weighing ≥50kg). The total 
LCM daily dose for IIL subjects should be 2mg/kg/day (subjects weighing <50kg) or 100mg/day 
(subjects weighing ≥50kg) and should remain constant for at least 7 days prior to a LCM dose 
increase. 
During the Treatment Period, blood samples will be obtained for pharmacokinetic (PK) analysis, 
and detailed safety assessments will be performed. 
The timing of the End-of-Study/Final Visit will depend on the timing of the last LCM infusion or 
withdrawal from the Treatment Period and available time to complete all assessments. The Final 
Visit can be conducted on the same day as the last dose if the last LCM infusion was performed 
in the morning, and time permits completion of assessments. Otherwise, the Final Visit should be 
conducted the day following the last dose of iv LCM after completion of or withdrawal from the 
Treatment Period. The safety follow-up Telephone Contact 1 should occur 1 to 3 days after the 
Final Visit for all subjects. 
For RxL and IIL subjects who are eligible and choose to continue LCM treatment in SP848, a 
Transition Visit will be conducted either concurrent with the Final Visit or separately. Oral LCM 
solution will be provided for these subjects to allow continuity of LCM therapy after the final 
LCM infusion and the subject’s Transition Visit in EP0060 and Visit 1 for SP848.
For RxL and IIL subjects who will not continue LCM treatment in SP848, an additional safety 
follow-up Telephone Contact 2 should occur 30 days (±2 days) after the last iv dose of study 
LCM treatment.
The maximum study durations are as follows:
x Approximately 16 days:
 Subjects in the OLL group will resume participation in their respective study and 
either resume oral LCM treatment or follow taper regimen as described in the long-
term, open-label study accordingly.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 209 of 240
x Approximately 23 days
 Subjects in the RxL or IIL groups who, if determined clinically appropriate, are given 
the option to continue oral LCM treatment in SP848.
x Approximately 45 days:
 Subjects in the RxL or IIL groups who will not continue oral LCM treatment in 
SP848. 
Subjects should continue antiepileptic drug (AED) treatment at the discretion of the treating 
physician. For RxL and IIL subjects who will discontinue use of LCM, the subject should 
complete the EP0060 Final Visit and either refer to the long-term, open-label studies taper 
regimen or taper at the discretion of the treating physician.
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator, Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes. 
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator, Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 210 of 240
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes. 
x OR Cohort 2 should be stopped, 
x AND whether to initiate the assessment of safety in younger pediatric subjects (≥1 month to 
<4 years of age).
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. A completer for this study is 
defined as a subject who completes at least 1 visit with iv LCM treatment and the associated 
assessments for that visit (eg, PK samples, vital signs, 12-lead ECG).
Has been changed to:
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of 
intravenous (iv) lacosamide (LCM; VIMPAT®) infusions in pediatric subjects ≥1 month to <17 
years of age with epilepsy. Investigation the use of iv LCM in pediatric subjects with epilepsy ≥1 
month to <4 years of age is planned.
EP0060 will include approximately 100 subjects. The following subjects will be eligible for 
enrollment in EP0060:
x Open-label LCM (OLL) subjects: currently receiving oral LCM as adjunctive or 
monotherapy as participants in an open-label long-term study (SP848, EP0034, or other 
pediatric study).
x Prescribed-LCM (RxL) subjects: currently receiving prescribed oral LCM from 
commercial supply (eg, VIMPAT) as adjunctive or monotherapy.
x Initiating iv LCM (IIL) subjects: not currently receiving LCM and will receive iv LCM as 
adjunctive treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL 
subjects.
Subjects can receive iv LCM as follows: 
x Replacement for oral LCM treatment (OLL and RxL subjects): 
 Clinical need administration: Subjects currently taking prescribed oral LCM (or any 
enteric LCM administration, eg, LCM administration by feeding tube) who need to 
undergo a procedure and are treated at an epilepsy monitoring unit (EMU) or health 
care facility, or other situations where iv administration is clinically appropriate and 
oral administration is not feasible (ie, surgery). In these subjects, the maximum 
number of iv doses of LCM is 10. 
 Elective administration: Subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) and elect to receive iv LCM 
administration at an EMU or healthcare facility. In these subjects, the maximum 
number of iv doses of LCM is 2.
x Adjunctive iv LCM treatment initiation (IIL subjects):
 Clinical need administration: Subjects not currently taking LCM who need to undergo 
a procedure, be treated at an EMU or health care facility, or other situations where iv 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 211 of 240
administration is clinically appropriate and oral administration is not feasible (ie, 
surgery). In these subjects, the maximum number of iv doses of LCM is 10.
 Elective administration: Subjects not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
Pediatric subjects entering into EP0060 from the OLL group will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll into 
EP0060 from the RxL group will temporarily switch from their prescribed oral LCM treatment to 
the iv LCM formulation. Subjects in the IIL group will initiate adjunctive treatment with iv 
LCM. After completion of this study, eligible subjects from the RxL and IIL groups will have the 
option to continue LCM treatment in SP848. Subjects will be enrolled from approximately 40 
sites in North America, Europe, and Asia. Additional sites or regions may be added if deemed 
necessary.
The primary objective of EP0060 is to evaluate the safety and tolerability of iv LCM infusion(s) 
in pediatric subjects ≥1 month to <17 years with epilepsy. EP0060 is planned to include up to 
2 age-based cohorts with Cohort 1 including at least 40 subjects who are ≥8 to <17 years and 
Cohort 2 including approximately 44 subjects who are ≥1 month to <8 years. Within Cohort 1, 
at least 20 subjects will be ≥12 to <17 years of age and at least 20 subjects will be ≥8 to <12 
years of age. Within Cohort 2, every attempt will be made to enroll 20 subjects ≥4 to <8 
years of age, 12 subjects ≥2 to <4 years of age, and 12 subjects ≥1 month to <2 years of age.
A Data Monitoring Committee (DMC) will review the safety and tolerability data for each 
cohort to make the following recommendations: the progression of the current cohort, including 
iv infusion durations to be evaluated, and progression to initiate enrollment in the next cohort 
(Cohort 2) or separate study for the evaluation of iv LCM in children <4 years of age (as detailed 
further below).
EP0060 is comprised of the following study periods: 
x For all subjects:
 Screening and/or Baseline Period (up to 7 days),
 Treatment Period
(1) Clinical need administration: up to 10 doses or up to 5 days
(2) Elective administration: up to 2 consecutive doses over approximately 24 hours
 End-of-Study/Final Visit (1 day), 
 End-of-Study/Telephone Contact 1 (1 to 3 days),
x 
Additional visits or contacts as follows:
 RxL and IIL subjects who are eligible and choose to continue oral LCM treatment for 
up to 2 years in SP848
◦ 
Transition Visit, which can be concurrent with Final Visit or separate (up to 
7 days after Final Visit)
 RxL and IIL subjects who do not continue LCM treatment in SP848
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 212 of 240
◦ 
End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM). 
For all subjects, the Screening, Baseline, Treatment Period, and Final Visit may occur in 1 day, 
provided the subject only requires 1 iv infusion, results of examinations (ie, 12-lead 
electrocardiogram [ECG], laboratory measurements) are available to allow verification of subject 
eligibility prior to infusion, and time permits for completion of Final Visit assessments. 
If further time is required for Screening assessments or to obtain results, the Screening Period 
can last up to 7 days. For OLL and RxL subjects, oral LCM will be administered during this time 
from their open-label study or prescribed LCM supply in accordance with each subject’s oral 
LCM dosage regimen. For IIL subjects, no LCM will be administered during the Screening 
Period.
During the Treatment Period, at least 1 dose of iv LCM will be administered. If more than 
1 infusion is given, infusions will occur twice daily (bid) at approximately 12-hour intervals for 
up to 10 doses (or up to 5 days for clinical need administration or up to 2 consecutive doses [over 
approximately 24 hours]) for elective administration. For OLL and RxL subjects, the daily dose 
of iv LCM will be the same as the subject's current stable daily dose of oral LCM (2 to 
12mg/kg/day or 100 to 600mg/day). The maximum dose permitted in this study for OLL and 
RxL subjects is 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, the iv LCM 
dose will be 1mg/kg bid (subjects weighing <50kg) or 50mg bid (subjects weighing ≥50kg). The 
total LCM daily dose for IIL subjects should be 2mg/kg/day (subjects weighing <50kg), or
100mg/day (subjects weighing ≥50kg) and should remain constant for at least 7 days prior to a 
LCM dose increase. 
During the Treatment Period, blood samples will be obtained for pharmacokinetic (PK) analysis, 
and detailed safety assessments will be performed. 
The timing of the End-of-Study/Final Visit will depend on the timing of the last LCM infusion or
withdrawal from the Treatment Period and available time to complete all assessments. The Final 
Visit can be conducted on the same day as the last dose of iv LCM if the last LCM infusion was 
performed in the morning, and time permits to complete all assessments. Otherwise, the Final 
Visit should be conducted the day following the last dose of iv LCM after completion of or 
withdrawal from the Treatment Period. The safety follow-up Telephone Contact 1 should occur 1 
to 3 days after the Final Visit for all subjects. 
For RxL and IIL subjects who are eligible and choose to continue LCM treatment in SP848, a 
Transition Visit will be conducted either concurrent with the Final Visit or separately. Oral LCM 
solution will be provided for these subjects to allow continuity of LCM therapy after the final 
LCM infusion and the subject’s Transition Visit in EP0060 and Visit 1 for SP848.
For RxL and IIL subjects who will not continue LCM treatment in SP848, an additional safety 
follow-up Telephone Contact 2 should occur 30 days (±2 days) after the last iv dose of study 
LCM treatment.
The maximum study durations are as follows:
x Approximately 16 days:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 213 of 240
 Subjects in the OLL group will resume participation in their respective study and 
either resume oral LCM treatment or follow taper regimen as described in the long-
term, open-label study accordingly.
x Approximately 23 days
 Subjects in the RxL or IIL groups who, if determined clinically appropriate, are given 
the option to continue oral LCM treatment in SP848.
x Approximately 45 days:
 Subjects in the RxL or IIL groups who will not continue oral LCM treatment in 
SP848. 
Subjects should continue antiepileptic drug (AED) treatment at the discretion of the treating 
physician. For RxL and IIL subjects who will discontinue use of LCM, the subject should 
complete the EP0060 Final Visit and either refer to the long-term, open-label studies taper 
regimen or taper at the discretion of the treating physician.
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes. 
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to 
receive iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a duration 
of 30 minutes but no longer than 60 minutes whenever possible.
After completion of the first 20 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 214 of 240
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes. 
x OR approximately 30 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes. 
x OR Cohort 2 should be stopped.
x AND whether to initiate the assessment of safety in younger pediatric subjects (≥1 month to 
<4 years of age). 
This design will result in a total exposure of approximately 100 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. A completer for this study is 
defined as a subject who completes at least 1 visit with iv LCM treatment and the associated 
assessments for that visit (eg, PK samples, vital signs, 12-lead ECG).
Change #6
Section 2 INTRODUCTION, sixth paragraph
In the US, the iv formulation of LCM is approved in patients ≥17 years of age at a maximum 
dose of 400mg/day as monotherapy and adjunctive therapy in the treatment of partial onset 
seizures in subjects with epilepsy when oral administration is temporarily not feasible. In EU, the 
iv formulation is approved in patients ≥16 years at a maximum dose of 600mg/day as 
monotherapy (EU CHMP positive opinion received on 11 Nov 2016) and at a maximum dose of 
400mg/day as adjunctive therapy in the treatment of partial onset seizures in subjects with 
epilepsy when oral administration is temporarily not feasible. Intravenous LCM is approved in 
patients ≥16 years of age and for infusion durations of 15 to 60 minutes depending on the 
country-specific labeling. 
Has been changed to:
In the US, oral tablets and oral solution (syrup) of LCM are indicated for the treatment of 
partial-onset seizures in patients 4 years of age and older. As the safety of LCM injection 
for iv use has not been established in pediatric patients, LCM injection for iv use at
infusion durations of 15 to 60 minutes is indicated for the treatment of partial-onset 
seizures only in patients 17 years of age and older as an alternative when oral administration is 
temporarily not feasible. 
Additionally, LCM has been approved in the EU (oral tablets, oral solution [syrup], and 
solution for iv infusion), as monotherapy and adjunctive therapy in the treatment of 
partial-onset seizures with or without secondary generalization in patients 4 years of age 
and older. The iv formulation at infusion durations of 15 to 60 minutes is approved as an 
alternative for patients when oral administration is temporarily not feasible.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 215 of 240
Change #7
Section 2 INTRODUCTION, ninth paragraph
The results of EP0060 will provide safety, tolerability, and PK data regarding the use of the 
iv LCM formulation either as replacement for oral LCM or for adjunctive LCM treatment 
initiation in pediatric subjects ≥4 to <17 years with epilepsy.
Has been changed to:
The results of EP0060 will provide safety, tolerability, and PK data regarding the use of the 
iv LCM formulation either as replacement for oral LCM or for adjunctive LCM treatment 
initiation in pediatric subjects ≥1 month to <17 years with epilepsy.
Change #8
Section 3 STUDY OBJECTIVE(S)
The primary objective of this study is to evaluate the safety and tolerability of iv LCM 
infusion(s) in pediatric subjects ≥4 to <17 years with epilepsy. An additional objective is to 
evaluate the PK of iv LCM in pediatric subjects with epilepsy. 
Has been changed to:
The primary objective of this study is to evaluate the safety and tolerability of iv LCM 
infusion(s) in pediatric subjects ≥1 month to <17 years with epilepsy. An additional objective is 
to evaluate the PK of iv LCM in pediatric subjects with epilepsy. 
Change #9
Section 4.3 Pharmacokinetic variable(s)
4.3 Pharmacokinetic variable(s)
The PK variables will include plasma concentration of LCM and its main metabolite, 
SPM 12809.
Has be changed to:
4.3 Other pharmacokinetic variable(s)
The other PK variables will include plasma concentration of LCM and its main metabolite, 
SPM 12809.
Change #10
Section 5.1 Study description
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of iv 
LCM infusions in pediatric subjects ≥4 to <17 years of age with epilepsy. EP0060 will include 
approximately 75 subjects. The following subjects will be eligible for enrollment in EP0060:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 216 of 240
x OLL subjects: currently receiving oral LCM as adjunctive or monotherapy as participants
in an open-label long-term study (SP848, EP0034, or other pediatric study).
x RxL subjects: currently receiving prescribed oral LCM from commercial supply (eg, 
VIMPAT) as adjunctive or monotherapy.
x IIL subjects: not currently receiving LCM and will receive iv LCM as adjunctive 
treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL subjects.
Subjects can receive iv LCM as follows:
x Replacement for oral LCM treatment (OLL and RxL subjects): 
 Clinical need administration: subjects currently taking prescribed oral LCM (or any 
enteric LCM administration, eg, LCM administration by feeding tube) who need to 
undergo a procedure and are treated at an EMU or health care facility, or other 
situations where iv administration is clinically appropriate and oral administration is 
not feasible (ie, surgery). In these subjects, the maximum number of iv doses of LCM 
is 10.
 Elective administration: subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) and elect to receive iv LCM 
administration at an EMU or healthcare facility. In these subjects, the maximum 
number of iv doses of LCM is 2. 
x Adjunctive iv LCM treatment initiation (IIL subjects):
 Clinical need administration: subjects not currently taking LCM who need to undergo 
a procedure, be treated at an EMU or health care facility, or other situations where iv 
administration is clinically appropriate and oral administration is not feasible (ie, 
surgery). In these subjects, the maximum number of iv doses of LCM is 10.
 Elective administration: subjects not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
Pediatric subjects entering into EP0060 from the OLL group will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll into 
EP0060 from the RxL group will temporarily switch from their prescribed oral LCM treatment to 
the iv LCM formulation while subjects in the IIL group will initiate adjunctive treatment with iv 
LCM. After completion of this study, eligible subjects from the RxL and IIL groups will have the 
option to continue LCM treatment in SP848. Subjects will be enrolled from approximately 40 
sites in North America and Europe. Additional sites or regions may be added if deemed 
necessary.
EP0060 is planned to include up to 2 age-based cohorts with Cohort 1 including at least 
40 subjects who are ≥8 to <17 years and Cohort 2 including at least 20 subjects who are ≥4 to 
<8 years. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age and at least 
20 subjects will be ≥8 to <12 years of age. A DMC will review the safety and tolerability data for 
each cohort to make the following recommendations: the progression of the current cohort, 
including iv infusion durations to be evaluated, and progression to initiate enrollment in the next 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 217 of 240
cohort (Cohort 2) or separate study for the evaluation of iv LCM in children <4 years of age. 
Details regarding the DMC are provided in Section 12.7.2.
EP0060 is comprised of the following study periods: 
x For all subjects:
 Screening and/or Baseline Period (up to 7 days),
 Treatment Period
(1) Clinical need administration (see above in this Section): up to 10 doses or up to 5 
days
(2) Elective administration (see above in this Section): up to 2 consecutive doses over 
approximately 24 hours
 End-of-Study/Final Visit (1 day), 
 End-of-Study/Telephone Contact 1 (1 to 3 days),
x 
Additional visits or contacts as follows:
 RxL and IIL subjects who are eligible and choose to continue oral LCM treatment for 
up to 2 years in SP848
◦ 
Transition Visit, which can be concurrent with Final Visit or separate (up to 7 
days after Final Visit)
 RxL and IIL subjects who do not continue LCM treatment in SP848
◦ 
End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM).
For all subjects, the Screening, Baseline, Treatment Period, and Final Visit may occur in 1 day, 
provided the subject only requires 1 iv infusion, results of examinations (ie, ECG, laboratory 
measurements) are available to allow verification of subject eligibility prior to infusion, and time 
permits for completion of Final Visit assessments. 
If further time is required for Screening assessments or to obtain results, the Screening Period 
can last up to 7 days. For OLL and RxL subjects, oral LCM will be administered during this time 
from their open-label study or prescribed LCM supply in accordance with each subject’s oral 
LCM dosage regimen. For IIL subjects, no LCM will be administered during the Screening 
Period.
During the Treatment Period, at least 1 dose of iv LCM will be administered. If more than 
1 infusion is given, infusions will occur twice daily (bid) at approximately 12-hour intervals for 
up to 10 doses (or up to 5 days) for clinical need administration or up to 2 consecutive doses 
(over approximately 24 hours) for elective administration. For OLL and RxL subjects, the daily 
dose of iv LCM will be the same as the subject's current stable daily dose of oral LCM (2 to 
12mg/kg/day or 100 to 600mg/day). The maximum dose permitted in this study for OLL and 
RxL subjects is 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, the iv LCM 
dose will be 1mg/kg (subjects weighing <50kg) or 50mg (subjects weighing ≥50kg). The total 
LCM daily dose for IIL subjects should be 2mg/kg/day (subjects weighing <50kg) or 100mg/day 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 218 of 240
(subjects weighing ≥50kg) and should remain constant for at least 7 days prior to a LCM dose 
increase. 
During the Treatment Period, blood samples will be obtained for PK analysis, and safety 
assessments will be performed (AEs, physical and neurological exams, pulse rate, BP, 12-lead 
ECG, clinical hematology and chemistry, and Columbia-Suicide Severity Rating Scale [C-SSRS] 
when applicable). 
The timing of the End-of-Study/Final Visit will depend on the timing of the last LCM infusion or 
withdrawal from the Treatment Period and available time to complete all assessments. The Final 
Visit can be conducted on the same day as the last dose if the last LCM infusion was performed 
in the morning, and time permits completion of assessments. Otherwise, the Final Visit should be 
conducted the day following the last dose of iv LCM after completion of or withdrawal from the 
Treatment Period. The safety follow-up Telephone Contact 1 should occur 1 to 3 days after the 
Final Visit for all subjects. 
For RxL and IIL subjects who are eligible and choose to continue LCM treatment in SP848, a 
Transition Visit will be conducted either concurrent with the Final Visit or separately. Oral LCM 
solution will be provided for these subjects to allow continuity of LCM therapy after the final 
LCM infusion and the subject’s Transition Visit in EP0060 and Visit 1 for SP848. 
For RxL and IIL subjects who will not continue LCM treatment in SP848, an additional safety 
follow-up Telephone Contact 2 should occur 30 days (±2 days) after the last iv dose of study 
LCM treatment.
The maximum study durations are as follows:
x Approximately 16 days:
 Subjects in the OLL group will resume participation in their respective study and 
either resume oral LCM treatment or follow taper regimen as described in the long-
term, open-label study accordingly.
x Approximately 23 days
 Subjects in the RxL or IIL groups who, if determined clinically appropriate, are given 
the option to continue oral LCM treatment in SP848.
x Approximately 45 days:
 Subjects in the RxL or IIL groups who will not continue oral LCM treatment in 
SP848. 
Subjects should continue AED treatment at the discretion of the treating physician. For RxL and 
IIL subjects who directly enrolled and will discontinue use of LCM, the subject should complete 
the EP0060 Final Visit and either refer to the long-term, open-label studies taper regimen or 
taper at the discretion of the treating physician.
The schedule of study assessments is provided in Section 5.2.
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 219 of 240
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes.
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make
recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes.
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR Cohort 2 should be stopped, 
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. A completer for this study is 
defined as a subject who completes at least 1 visit with iv LCM treatment and the associated 
assessments for that visit (eg, PK samples, vital signs, 12-lead ECG).
Has been changed to:
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of iv 
LCM infusions in pediatric subjects ≥1 month to <17 years of age with epilepsy. EP0060 will 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 220 of 240
include approximately 100 subjects. The following subjects will be eligible for enrollment in 
EP0060:
x OLL subjects: currently receiving oral LCM as adjunctive or monotherapy as participants 
in an open-label long-term study (SP848, EP0034, or other pediatric study).
x RxL subjects: currently receiving prescribed oral LCM from commercial supply (eg, 
VIMPAT) as adjunctive or monotherapy.
x IIL subjects: not currently receiving LCM and will receive iv LCM as adjunctive 
treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL subjects.
Subjects can receive iv LCM as follows:
x Replacement for oral LCM treatment (OLL and RxL subjects): 
 Clinical need administration: subjects currently taking prescribed oral LCM (or any 
enteric LCM administration, eg, LCM administration by feeding tube) who need to 
undergo a procedure and are treated at an EMU or health care facility, or other 
situations where iv administration is clinically appropriate and oral administration is 
not feasible (ie, surgery). In these subjects, the maximum number of iv doses of LCM 
is 10.
 Elective administration: subjects currently taking oral LCM (or any enteric LCM 
administration, eg, LCM administration by feeding tube) and elect to receive iv LCM 
administration at an EMU or healthcare facility. In these subjects, the maximum 
number of iv doses of LCM is 2. 
x Adjunctive iv LCM treatment initiation (IIL subjects):
 Clinical need administration: subjects not currently taking LCM who need to undergo 
a procedure, be treated at an EMU or health care facility, or other situations where iv 
administration is clinically appropriate and oral administration is not feasible (ie, 
surgery). In these subjects, the maximum number of iv doses of LCM is 10.
 Elective administration: subjects not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these subjects, the 
maximum number of iv doses of LCM is 2.
Pediatric subjects entering into EP0060 from the OLL group will temporarily suspend their 
participation in that study to receive iv LCM treatment in EP0060. Subjects who enroll into 
EP0060 from the RxL group will temporarily switch from their prescribed oral LCM treatment to 
the iv LCM formulation while subjects in the IIL group will initiate adjunctive treatment with iv 
LCM. After completion of this study, eligible subjects from the RxL and IIL groups will have the 
option to continue LCM treatment in SP848. Subjects will be enrolled from approximately 40 
sites in North America, Europe, and Asia. Additional sites or regions may be added if deemed 
necessary.
EP0060 is planned to include up to 2 age-based cohorts with Cohort 1 including at least 
40 subjects who are ≥8 to <17 years and Cohort 2 including approximately 44 subjects who are 
≥1 month to <8 years. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age and 
at least 20 subjects will be ≥8 to <12 years of age. Within Cohort 2, every attempt will be 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 221 of 240
made to enroll 20 subjects ≥4 to <8 years of age, 12 subjects ≥2 to <4 years of age, and 12 
subjects ≥1 month to <2 years of age.
A DMC will review the safety and tolerability data for each cohort to make the following 
recommendations: the progression of the current cohort, including iv infusion durations to be 
evaluated, and progression to initiate enrollment in the next cohort (Cohort 2) or separate study 
for the evaluation of iv LCM in children <4 years of age. Details regarding the DMC are 
provided in Section 12.7.2.
EP0060 is comprised of the following study periods: 
x For all subjects:
 Screening and/or Baseline Period (up to 7 days),
 Treatment Period
(1) Clinical need administration (see above in this Section): up to 10 doses or up to 5 
days
(2) Elective administration (see above in this Section): up to 2 consecutive doses over 
approximately 24 hours
 End-of-Study/Final Visit (1 day), 
 End-of-Study/Telephone Contact 1 (1 to 3 days),
x 
Additional visits or contacts as follows:
 RxL and IIL subjects who are eligible and choose to continue oral LCM treatment for 
up to 2 years in SP848
◦ 
Transition Visit, which can be concurrent with Final Visit or separate (up to 7 
days after Final Visit)
 RxL and IIL subjects who do not continue LCM treatment in SP848
◦ 
End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM).
For all subjects, the Screening, Baseline, Treatment Period, and Final Visit may occur in 1 day, 
provided the subject only requires 1 iv infusion, results of examinations (ie, ECG, laboratory 
measurements) are available to allow verification of subject eligibility prior to infusion, and time 
permits for completion of Final Visit assessments. 
If further time is required for Screening assessments or to obtain results, the Screening Period 
can last up to 7 days. For OLL and RxL subjects, oral LCM will be administered during this time 
from their open-label study or prescribed LCM supply in accordance with each subject’s oral 
LCM dosage regimen. For IIL subjects, no LCM will be administered during the Screening 
Period.
During the Treatment Period, at least 1 dose of iv LCM will be administered. If more than 
1 infusion is given, infusions will occur twice daily (bid) at approximately 12-hour intervals for 
up to 10 doses (or up to 5 days) for clinical need administration or up to 2 consecutive doses 
(over approximately 24 hours) for elective administration. For OLL and RxL subjects, the daily 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 222 of 240
dose of iv LCM will be the same as the subject's current stable daily dose of oral LCM (2 to 
12mg/kg/day or 100 to 600mg/day). The maximum dose permitted in this study for OLL and 
RxL subjects is 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, the iv LCM 
dose will be 1mg/kg bid (subjects weighing <50kg) or 50mg bid (subjects weighing ≥50kg). The 
total LCM daily dose for IIL subjects should be 2mg/kg/day (subjects weighing <50kg), or
100mg/day (subjects weighing ≥50kg) and should remain constant for at least 7 days prior to a 
LCM dose increase.
During the Treatment Period, blood samples will be obtained for PK analysis, and safety 
assessments will be performed (AEs, physical and neurological exams, pulse rate, BP, 12-lead 
ECG, clinical hematology and chemistry, and Columbia-Suicide Severity Rating Scale [C-SSRS] 
when applicable). 
The timing of the End-of-Study/Final Visit will depend on the timing of the last LCM infusion or 
withdrawal from the Treatment Period and available time to complete all assessments. The Final 
Visit can be conducted on the same day as the last dose of iv LCM if the last LCM infusion was 
performed in the morning, and time permits to complete all assessments. Otherwise, the Final 
Visit should be conducted the day following the last dose of iv LCM after completion of or 
withdrawal from the Treatment Period. The safety follow-up Telephone Contact 1 should occur 1 
to 3 days after the Final Visit for all subjects. 
For RxL and IIL subjects who are eligible and choose to continue LCM treatment in SP848, a 
Transition Visit will be conducted either concurrent with the Final Visit or separately. Oral LCM 
solution will be provided for these subjects to allow continuity of LCM therapy after the final 
LCM infusion and the subject’s Transition Visit in EP0060 and Visit 1 for SP848. 
For RxL and IIL subjects who will not continue LCM treatment in SP848, an additional safety 
follow-up Telephone Contact 2 should occur 30 days (±2 days) after the last iv dose of study 
LCM treatment.
The maximum study durations are as follows:
x Approximately 16 days:
 Subjects in the OLL group will resume participation in their respective study and 
either resume oral LCM treatment or follow taper regimen as described in the long-
term, open-label study accordingly.
x Approximately 23 days
 Subjects in the RxL or IIL groups who, if determined clinically appropriate, are given 
the option to continue oral LCM treatment in SP848.
x Approximately 45 days:
 Subjects in the RxL or IIL groups who will not continue oral LCM treatment in 
SP848. 
Subjects should continue AED treatment at the discretion of the treating physician. For RxL and 
IIL subjects who directly enrolled and will discontinue use of LCM, the subject should complete 
the EP0060 Final Visit and either refer to the long-term, open-label studies taper regimen or 
taper at the discretion of the treating physician.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 223 of 240
The schedule of study assessments is provided in Section 5.2.
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but no longer than 60 minutes whenever 
possible. 
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes.
x OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR study should be stopped, 
x AND whether Cohort 2 can be initiated.
For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to 
receive iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a duration 
of 30 minutes but no longer than 60 minutes whenever possible.
After completion of the first 20 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes.
x OR approximately 30 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
x OR Cohort 2 should be stopped. 
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).
This design will result in a total exposure of approximately 100 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. A completer for this study is 
defined as a subject who completes at least 1 visit with iv LCM treatment and the associated 
assessments for that visit (eg, PK samples, vital signs, 12-lead ECG).
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 224 of 240
Change #11
Section 5.1.2 Planned number of subjects and site(s)
Approximately 75 subjects will be enrolled at approximately 40 sites.
The following cohorts are planned:
x Cohort 1: at least 40 subjects from ≥8 to <17 years of age, with at least 20 subjects from 
≥12 to <17 years of age and at least 20 subjects from ≥8 to <12 years of age
x Cohort 2: at least 20 subjects from ≥4 to <8 years of age 
The remaining subjects may be enrolled in either of the 2 cohorts.
Has been changed to:
Approximately 100 subjects will be enrolled at approximately 40 sites.
The following cohorts are planned:
x Cohort 1: at least 40 subjects from ≥8 to <17 years of age, with at least 20 subjects from 
≥12 to <17 years of age and at least 20 subjects from ≥8 to <12 years of age
x Cohort 2: every attempt will be made to enroll 20 subjects ≥4 to <8 years of age, 12 
subjects ≥2 to <4 years of age, and 12 subjects ≥1 month to <2 years of age.
The remaining subjects may be enrolled in either of the 2 cohorts.
Change #12
Section 5.1.3 Anticipated regions and countries
The study will be conducted at selected sites from North America and Europe. Additional sites 
may be added as deemed necessary.
Has been changed to:
The study will be conducted at selected sites from North America, Europe, and Asia. Additional 
sites or regions may be added as deemed necessary.
Change #13
Table 5–1 Schedule of study assessments, Clinical chemistry and hematology, Unscheduled 
Visit column
Clinical chemistry and 
hematologyp
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 225 of 240
Change #14
Table 5–1 Schedule of study assessments, footnote c
c If iv LCM treatment is continued after Day 1, assessments for Visit 3 must be completed for 
each infusion of iv LCM treatment in EP0060, unless otherwise noted (see footnote o).
Has been changed to:
c If iv LCM treatment is continued after Day 1, assessments for Visit 3 (excluding PK blood 
sampling [see footnote u]) must be completed for each infusion of iv LCM treatment in 
EP0060, unless otherwise noted (see footnote o).
Change #15
Table 5-1 Schedule of study assessments, footnote e
e A Final Visit must be completed for all subjects who complete or withdraw prematurely from 
EP0060. If the last iv infusion of LCM for the study occurs in the morning, the Final Visit may 
occur on the same day as the last infusion, time permitting. Otherwise, the Final Visit should 
occur on the following day (ie, last infusion in evening). For subjects who will discontinue use of 
LCM, the subject should complete the EP0060 Final Visit and either refer to the long-term, 
open-label studies taper regimen or taper at the discretion of the treating physician for those 
subjects who enrolled directly.
Has been changed to:
e A Final Visit must be completed for all subjects who complete or withdraw prematurely from 
EP0060. If the last iv infusion of LCM for the study occurs in the morning, The Final Visit may 
occur on the same day as the last dose of iv LCM, time permitting. Otherwise, the Final Visit 
should occur on the following day (ie, last infusion in evening). For subjects who will 
discontinue use of LCM, the subject should complete the EP0060 Final Visit and either refer to 
the long-term, open-label studies taper regimen for OLL subjects or taper at the discretion of 
the treating physician for RxL subjects those subjects who enrolled directly.
Change #16
Table 5-1 Schedule of study assessments, footnote j
j Procedure history, medical history, diagnosis of epilepsy, and childbearing potential will be 
collected for RxL and IIL subjects at Screening. For OLL subjects, a medical history update will 
be performed in order to collect medical history that was not captured during the course of the 
prior study.
Has been changed to:
j Procedure history, medical history, diagnosis of epilepsy, and childbearing potential will be 
collected for RxL and IIL subjects at Screening. For OLL subjects, a medical history update will 
be captured in the previous long-term open-label study and not in EP0060.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 226 of 240
Change #17
Table 5-1 Schedule of study assessments, new footnote q
q Bicarbonate testing is optional for subjects weighing less than 8kg. Consider testing for 
bicarbonate in subjects weighing less than 8kg in cases of suspected metabolic disturbances such 
as metabolic acidosis.
Has been added and subsequent footnotes have been renumbered.
Change #18
Table 5-1 Schedule of study assessments, footnote z
z For RxL and IIL subjects who are eligible and wish to enroll in SP848, a short-term oral LCM 
solution will be dispensed to allow continuity of LCM treatment while visits and assessments are 
scheduled for starting SP848. Subjects (or their caregivers) will administer the oral LCM 
solution twice a day according to the investigator’s instructions until the subject returns for the 
Transition Visit.
Has been changed to:
z For RxL and IIL subjects who are eligible and wish to enroll in SP848, a short-term oral LCM 
solution will be dispensed to allow continuity of LCM treatment while visits and assessments are 
scheduled for starting SP848. Subjects (or their caregivers) will administer the oral LCM 
solution twice a day, starting approximately 12 hours after the final iv LCM infusion,
according to the investigator’s instructions until the subject returns for the Transition Visit.
Change #19
Section 5.3 Rationale for study design and selection of dose
EP0060 is an open-label, multicenter study to investigate the safety and tolerability of iv LCM in 
pediatric subjects with epilepsy aged ≥4 to <17 years. A separate Phase 2/3 study investigating 
the use of iv LCM in pediatric subjects with epilepsy ≥1 month to <4 years of age is planned. 
The results of EP0060 will provide safety and PK data regarding the use of the iv LCM 
formulation in pediatric subjects (≥4 to <17 years of age). The EP0060 design is based on 
components of the study design for SP757, which evaluated iv LCM replacement in adults with 
partial-onset seizures, as well as based on design elements of other pediatric iv AED studies. In 
an effort to maximize the patient pool used in the evaluation of the safety of iv LCM in pediatric
subjects, Protocol Amendment 2 opened enrollment to also include OLL and RxL subjects who 
are on a stable dose of oral LCM and elect to receive iv LCM as well as IIL subjects who are not 
currently taking LCM and initiate adjunctive LCM treatment using iv LCM. This expansion of 
the subject population occurred prior to the start of study enrollment. Protocol Amendment 2 
also included the option for RxL and IIL subjects to continue oral LCM treatment after 
completion of iv LCM, if determined clinically appropriate, in SP848. If required, a short-term 
supply of oral LCM solution will be provided for RxL and IIL subjects transitioning to start 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 227 of 240
SP848 to ensure continuity of LCM treatment while allowing flexibility to schedule a clinical 
visit to initiate SP848. For RxL and IIL subjects who do not continue into SP848 (either by 
choice or not clinically appropriate), an additional telephone contact approximately 30 days after 
last dose of iv LCM IMP is added in order to collect final safety data. 
The iv LCM formulation is approved at doses of 200 to 400mg/day as adjunctive therapy in the 
treatment of partial-onset seizures in subjects ≥16 years of age (depending on country-specific 
labeling) with epilepsy when oral administration is temporarily not feasible, which can also 
include initiation of LCM treatment. 
A weight-based LCM dosing scheme for pediatric subjects is being evaluated in Phase 3 
double-blinded, placebo-controlled studies and targets similar LCM plasma concentrations as 
those observed in adults given 400mg/day. As such, the target doses of LCM for the Phase 3 
studies are 8 to 12mg/kg/day; however, subjects entering EP0060 can be on a wider range of 
LCM doses based on the ranges of doses allowed in the long-term, open-label studies (2 to 
12mg/kg/day or 100 to 600mg/day). Thus, the iv LCM doses being evaluated in EP0060 will 
range from 2 to 12mg/kg/day or 100 to 600mg/day for OLL and RxL subjects, with a maximum 
dose of 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, this range of doses 
above also includes the pediatric starting dose of 2mg/kg/day (subjects <50kg) or 100mg/day 
(subjects ≥50kg), which is the same as those used in the Phase 3 pediatric LCM studies. The 
LCM dose at initiation of treatment should remain constant for at least 7 days prior to a LCM 
dose increase.
EP0060 will initially enroll at least 40 older pediatric subjects (Cohort 1) and will include at least 
20 subjects ≥12 to <17 years of age and at least 20 subjects ≥8 to <12 years of age. Cohort 2 (at 
least 20 subjects ≥4 to <8 years of age) will follow sequentially based on DMC recommendation. 
After the first 20 subjects (Cohort 1) or 10 subjects (Cohort 2) have received iv LCM over 
infusion durations of 30 to 60 minutes, the DMC will review the available safety and tolerability 
data. Based on their review, the DMC will recommend the target infusion duration for the 
remaining subjects in the cohort (ie, 30 to 60 minutes for all remaining subjects or 15 to 30 
minutes [only for subjects who would directly benefit from an increased infusion rate, in the 
opinion of the investigator; otherwise 30 to 60 minutes]), if the study/cohort should be stopped, 
and if the next cohort can be initiated, and if a new iv LCM study in younger pediatric subjects 
(≥1 month to <4 years of age) can be initiated (Section 12.7.2).
This design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM in subjects ≥4 to <17 years of age over a range of infusion 
durations. 
Taken together, the iv LCM dosing scheme and planned target infusion durations being 
evaluated in EP0060 (2 to 12mg/kg/day or 100 to 600mg/day; 15 to 60 minutes) allow for 
administration of a range of pediatric doses, and include infusion durations that are the same as 
those approved for adults and adolescents. 
Has been changed to:
EP0060 is an open-label, multicenter study to investigate the safety and tolerability of iv LCM in 
pediatric subjects with epilepsy aged ≥1 month to <17 years. A separate Phase 2/3 study 
investigating the use of iv LCM in pediatric subjects with epilepsy ≥1 month to <4 years of age 
is planned. The results of EP0060 will provide safety and PK data regarding the use of the iv 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 228 of 240
LCM formulation in pediatric subjects (≥1 month to <17 years of age). The EP0060 design is 
based on components of the study design for SP757, which evaluated iv LCM replacement in 
adults with partial-onset seizures, as well as based on design elements of other pediatric iv AED 
studies. In an effort to maximize the patient pool used in the evaluation of the safety of iv LCM 
in pediatric subjects, EP0060 has opened enrollment to include also OLL and RxL subjects who 
are on a stable dose of oral LCM and elect to receive iv LCM as well as IIL subjects who are not 
currently taking LCM and initiate adjunctive LCM treatment using iv LCM. The expansion of 
the subject population occurred prior to the start of study enrollment. EP0060 also includes the 
option for RxL and IIL subjects to continue oral LCM treatment after completion of iv LCM, if 
determined clinically appropriate, in SP848. If required, a short-term supply of oral LCM 
solution will be provided for RxL and IIL subjects transitioning to start SP848 to ensure 
continuity of LCM treatment while allowing flexibility to schedule a clinical visit to initiate 
SP848. For RxL and IIL subjects who do not continue into SP848 (either by choice or not 
clinically appropriate), an additional telephone contact approximately 30 days after last dose of 
iv LCM IMP is added in order to collect final safety data. 
The iv LCM formulation at infusion durations of 15 to 60 minutes is approved at doses of 200 
to 400mg/day as adjunctive therapy in the treatment of partial-onset seizures in subjects ≥17
years of age (depending on country-specific labeling) with epilepsy when oral administration is 
temporarily not feasible, which can also include initiation of LCM treatment, for infusion 
durations of 15 to 60 minutes. Additionally in the EU, the iv formulation is also approved 
in pediatric subjects down to 4 years of age at maximum weight-based doses depending on 
weight band and whether LCM is administered as monotherapy or adjunctive therapy, for 
infusion durations of 15 to 60 minutes. An infusion duration of at least 30 minutes for 
administration >200mg per infusion (ie, >400mg/day) is preferred.
A weight-based LCM dosing scheme for pediatric subjects is being evaluated in Phase 3 
double-blinded, placebo-controlled studies and targets similar LCM plasma concentrations as 
those observed in adults given 400mg/day. As such, the target doses of LCM for the Phase 3 
studies are 8 to 12mg/kg/day; however, subjects entering EP0060 can be on a wider range of 
LCM doses based on the ranges of doses allowed in the long-term, open-label studies (2 to 
12mg/kg/day or 100 to 600mg/day). Thus, the iv LCM doses being evaluated in EP0060 will 
range from 2 to 12mg/kg/day or 100 to 600mg/day for OLL and RxL subjects, with a maximum 
dose of 12mg/kg/day or 600mg/day, whichever is lower. For IIL subjects, this range of doses 
above also includes the pediatric starting dose of 2mg/kg/day (subjects <50kg) or 100mg/day 
(subjects ≥50kg), which is the same as those used in the Phase 3 pediatric LCM studies. The 
LCM dose at initiation of treatment should remain constant for at least 7 days prior to a LCM 
dose increase.
EP0060 will initially enroll at least 40 older pediatric subjects (Cohort 1) and will include at least 
20 subjects ≥12 to <17 years of age and at least 20 subjects ≥8 to <12 years of age. Cohort 2 will 
enroll approximately 44 subjects (with every attempt to enroll 20 subjects ≥4 to <8 years of 
age, 12 subjects ≥2 to <4 years of age, and 12 subjects ≥1 month to <2 years of age) and will 
follow sequentially based on DMC recommendation. After completion of the first 20 subjects 
(Cohort 1) and after completion of 20 subjects (Cohort 2) have received iv LCM over infusion 
durations of 30 to 60 minutes, the DMC will review the available safety and tolerability data. 
Based on their review, the DMC will recommend the target infusion duration for the remaining 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 229 of 240
for subjects who would directly benefit from an increased infusion rate, in the opinion of the 
investigator; otherwise 30 to 60 minutes]), if the study/cohort should be stopped, and if the next 
cohort can be initiated, and if a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age) can be initiated (Section 12.7.2).
This design will result in a total exposure of approximately 100 pediatric subjects to assess the 
safety and tolerability of iv LCM in subjects ≥1 month to <17 years of age over a range of 
infusion durations. 
Taken together, the iv LCM dosing scheme and planned target infusion durations being 
evaluated in EP0060 (2 to 12mg/kg/day or 100 to 600mg/day; 15 to 60 minutes) allow for 
administration of a range of pediatric doses, and include infusion durations that are the same as 
those approved for adults and adolescents. 
Change #20
Section 6.1 Inclusion criteria, second criterion
2. Subject is male or female from ≥4 to <17 years of age.
Has been changed to:
2. Subject is male or female from ≥1 month to <17 years of age.
Change #21
Section 6.1 Inclusion criteria
8.  Subject weighs ≥4kg.
Has been added.
Change #22
Section 6.2 Exclusion criteria
20a. Subject is currently participating in another study of an IMP.
Has been added.
Change #23
Section 6.3.1 Potential drug-induced liver injury IMP discontinuation criteria, first 
paragraph and bullets
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: 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 230 of 240
x 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:
x Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and 
right upper quadrant pain or tenderness. Hypersensitivity symptoms include fever 
(without clear alternative cause), rash, or eosinophilia (ie, >5%).
The PDILI criterion below allows for subjects to continue on IMP at the discretion of the 
investigator. 
x 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).
Has been changed to:
Subjects with potential drug-induced liver injury (PDILI) must be assessed to determine if IMP 
must be immediately and permanently 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: 
x 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:
x Subjects with ALT or AST ≥3xULN who exhibit temporally associated symptoms of 
hepatitis or hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and 
right upper quadrant pain or tenderness. Hypersensitivity symptoms include fever 
(without clear alternative cause), rash, or eosinophilia (ie, >5%).
The PDILI criterion below requires discussion with Medical Monitor to decide whether 
subject is allowed to continue on IMP at the discretion of the investigator.
x 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).
Change #24
Section 7.2.1 Treatment Period, fifth paragraph
For the first 20 subjects ≥8 to <17 years of age enrolled into Cohort 1 and the first 10 subjects ≥4 
to <8 years in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no longer 
than 60 minutes whenever possible. 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 231 of 240
Has been changed to:
For the first 20 subjects ≥8 to <17 years of age enrolled into Cohort 1 and the first 20 subjects 
≥1 month to <8 years in Cohort 2, iv LCM should be infused over a duration of 30 minutes but 
no longer than 60 minutes whenever possible. 
Change #25
Section 7.2.1 Treatment Period, final paragraph
If subjects need to discontinue LCM, the subjects should be tapered off LCM either as specified 
in their long-term, open-label study or at the discretion of the treating physician for RxL and IIL 
subjects. For OLL subjects this taper should occur as a part of the long-term, open-label study 
and not as a part of EP0060.
Has been changed to:
If subjects need to discontinue LCM, OLL subjects should be tapered off LCM either as 
specified in their long-term, open-label study or at the discretion of the treating physician for 
RxL and IIL subjects. For OLL subjects, this taper should occur as a part of the long-term, 
open-label study and not as a part of EP0060.
Change #26
Section 8.1.1 Visit 1a and Visit 1b (Day -7 to Day 1) Screening and/or Baseline, fourth 
paragraph, sixth bullet
x Medical history update for OLL subjects from long-term open-label studies, or complete 
medical history for RxL and IIL subjects 
Has been changed to:
x Medical history update for OLL subjects from long-term open-label studies, or Complete 
medical history for RxL and IIL subjects (a medical history update will be captured in 
the previous long-term open-label study for OLL subjects) 
Change #27
Section 8.2.1 Visit 2 (Day 1), third paragraph, final bullet
For RxL and IIL subjects who are eligible and choose to participate in the long-term open-label 
oral LCM study SP848 after completion of EP0060, a short-term oral LCM solution will be 
dispensed at Visit 2. This supply is to allow continuity of LCM treatment after the last iv LCM 
infusion and the scheduled Transition Visit.
Has been changed to:  
For RxL and IIL subjects who are eligible and choose to participate in the long-term open-label 
oral LCM study SP848 after completion of EP0060, a short-term oral LCM solution will be 
dispensed at Visit 2. This supply is to allow continuity of LCM treatment after the last iv LCM 
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 232 of 240
infusion and the scheduled Transition Visit. Oral LCM solution administration should begin 
approximately 12 hours after the final iv LCM infusion.
Change #28
Section 8.4.1 Final Visit (Day 1 to 6)/Termination Visit, first paragraph
If the last iv infusion of LCM for the study occurs in the morning, the Final Visit may occur on 
the same day as the last infusion, time permitting. Otherwise, the Final Visit should occur on the 
following day (ie, last infusion in evening).
Has been Changed to:
If the last iv infusion of LCM for the study occurs in the morning, The Final Visit may occur on 
the same day as the last infusion, time permitting. Otherwise, the Final Visit should occur on the 
following day (ie, last infusion in evening).
Change #29
Section 8.4.1 Final Visit (Day 1 to 6)/Termination Visit, second paragraph, Oral LCM
administration, if applicable bullet, third dash
For RxL and IIL subjects who are eligible and wish to enroll in SP848, oral LCM administration 
may continue from the short-term oral LCM solution that was dispensed at Visit 2. Additional 
assessments will be conducted at the Transition Visit, as outlined in Section 8.4.3.
Has been changed to:
For RxL and IIL subjects who are eligible and wish to enroll in SP848, oral LCM administration
may continue from the short-term oral LCM solution that was dispensed at Visit 2, should begin 
approximately 12 hours after the final iv LCM infusion regardless of when the Final Visit 
occurs. Additional assessments will be conducted at the Transition Visit, as outlined in 
Section 8.4.3.
Change #30
Section 10.6.2 Liver function tests and evaluation of PDILI, seventh paragraph
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. 
Has been changed to:
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.
Change #31
Table 10-2 Laboratory tests, Clinical chemistry column, bicarbonate
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 233 of 240
a Bicarbonate testing is optional for subjects weighing less than 8kg. Consider testing for 
bicarbonate in subjects weighing less than 8kg in cases of suspected metabolic disturbances 
such as metabolic acidosis. 
Has been added.
Change #32
Table 10-3 Required investigations and follow up for PDILI, Immediate Actions column 
for ≥3xULN for ALT or AST
Immediate, temporary or permanent, IMP discontinuation.
Has been changed to:
Immediate, temporary or permanent, IMP discontinuation.
Change #33
Table 10-4 PDILI laboratory measurements, hematology measurements
Hematology
Eosinophil count
Has been changed to:
Hematology
Hematocrit
Hemoglobin
Platelet count
RBC count
WBC count
WBC differential count
Change #34
Table 10-4 PDILI laboratory measurements, chemistry measurements
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
Has been changed to:
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 234 of 240
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
ALT
AST
ALP
GGT
Albumin
Change #35
Section 10.7.3 Overall ECG interpretation
An immediate initial review of the ECGs will be conducted locally by the investigator, 
subinvestigator, or qualified designated reader. If this reading identifies abnormal ECG findings 
that are assessed by the investigator or subinvestigator to be clinically significant, then the ECG 
should be repeated in 1 hour, unless circumstances require a more rapid assessment. If the 
clinically significant abnormality is confirmed by the repeat ECG or if the investigator feels it is 
medically necessary, the subject must be withdrawn from EP0060 (see Section 6.3). The 
investigator may consult with the cardiologist at the central ECG laboratory to confirm the 
presence of a clinically significant ECG abnormality. It remains the responsibility of the 
investigator to decide whether an ECG finding is of clinical significance on the basis of the 
complete clinical picture and whether this finding influences the subject’s participation in 
EP0060.
Has been changed to:
An immediate initial review of the ECGs will be conducted locally by the investigator, 
subinvestigator, or qualified designated reader. If this reading identifies abnormal ECG findings 
that are assessed by the investigator or subinvestigator to be clinically significant, then the ECG 
should be repeated in 1 hour, unless circumstances require a more rapid assessment. If the 
clinically significant abnormality is confirmed by the repeat ECG or if the investigator feels it is 
medically necessary, the subject must be withdrawn from EP0060 (see Section 6.3). The 
investigator may consult with the cardiologist at the central ECG laboratory to confirm the 
presence of a clinically significant ECG abnormality. It remains the responsibility of the 
investigator to decide whether an ECG finding is of clinical significance on the basis of the 
complete clinical picture and whether this finding influences the subject’s participation in 
EP0060. Additionally, the ECGs will be sent to a central reader for review.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 235 of 240
Change #36
Section 12.1 Definition of analysis sets
The Safety Set iv (SS-iv) will include subjects who received at least 1 dose of iv LCM. The SS 
will be the primary analysis set for the analysis of safety data.
The Safety Set (SS) will include subjects who received at least 1 dose of LCM (oral or iv). 
Selected safety summaries will be presented for the SS.
The Pharmacokinetic-Per Protocol Set (PK-PPS) will include all subjects in the SS having 
provided at least 1 measurable postdose plasma sample (with recorded sampling time) on at least 
1 study day with documented LCM intake times.
Has been changed to:
The Safety Set (SS) will include subjects who received at least 1 dose of EP0060 study drug 
LCM (oral and/or iv). Selected safety summaries will be presented for the SS.
The Safety Set iv (SS-iv) will include subjects in the SS who received at least 1 dose of EP0060 
study drug iv LCM. The SS-iv will be the primary analysis set for the analysis of safety data.
The Pharmacokinetic-Per Protocol Set (PK-PPS) will include all subjects in the SS-iv having 
provided at least 1 measurable postdose plasma sample (with recorded sampling time) on at least 
1 study day with documented iv LCM intake times and without important protocol deviations 
impacting the interpretability of the PK analysis.
Change #37
Section 12.3 Planned pharmacokinetic analyses
Descriptive statistics for LCM and SPM 12809 plasma concentrations, including but not limited 
to geometric mean and CV, will be computed for pre-infusion and post-infusion time points on 
each infusion day where LCM and SPM 12809 plasma are collected. Data will be presented by 
cohort and infusion duration, and the IIL and OLL and RxL groups of subjects in EP0060 will 
also be presented.
Has been changed to:
Descriptive statistics for LCM and SPM 12809 plasma concentrations, including but not limited 
to geometric mean and CV, will be computed for pre-infusion and post-infusion time points on 
each infusion day where LCM and SPM 12809 plasma are collected. Data will be presented by 
cohort and infusion duration, and the IIL and OLL and RxL groups of subjects in EP0060 will 
also be presented. 
Change #38
Section 12.4 Planned safety analyses, first paragraph
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 236 of 240
Safety analyses will be presented by cohort and infusion duration, cohorts overall, and all 
subjects overall. Within cohort and infusion duration, the OLL and RxL groups of subjects and 
the IIL subject group will also be presented.
Has been changed to:
Safety analyses will be presented by age cohort and infusion duration, cohorts overall, and all 
subjects overall. Within cohort and infusion duration, the OLL and RxL groups of subjects and 
the IIL subject group will also be presented. 
Change #39
Section 12.5 Handling of protocol deviations, first sentence
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on the primary safety outcomes for an individual subject.
Has been changed to:
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on the primary safety outcomes for an individual subject.
Change #40
Section 12.6 Handling of dropouts or missing data
In Protocol Amendment 2, Section 12.6 Handling of dropouts or missing data was erroneously 
moved to become Section 17.1. This section has been restored to its original position and 
subsequent sections have been renumbered.
Change #41
Section 12.7 Planned interim analysis and data monitoring
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of the first 20 subjects in Cohort 1 and after completion of 
the first 10 subjects in Cohort 2. 
Has been changed to:
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of the first 20 subjects in Cohort 1 and after completion of 
the first 20 subjects in Cohort 2. 
Change #42
Section 12.7.2 Data Monitoring Committee, fourth paragraph through end of section
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 237 of 240
For Cohort 2, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion durations as follows: 
 15 minutes but no longer than 30 minutes only in subjects who would directly benefit
from an increased infusion rate, in the opinion of the investigator; OR,
 30 minutes but no longer than 60 minutes in subjects who would not directly benefit
from an increased infusion rate, in the opinion of the investigator
x OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 30 minutes but no longer than 60 minutes, 
x OR Cohort 2 should be stopped, 
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).
Has been changed to:
For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to 
receive iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a duration 
of 30 minutes but no longer than 60 minutes whenever possible.
After completion of the first 20 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows:
x EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion durations as follows: 
 15 minutes but no longer than 30 minutes only in subjects who would directly benefit
from an increased infusion rate, in the opinion of the investigator; OR,
 30 minutes but no longer than 60 minutes in subjects who would not directly benefit
from an increased infusion rate, in the opinion of the investigator
x OR approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 30 minutes but no longer than 60 minutes, 
x OR Cohort 2 should be stopped.
x AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 238 of 240
Change #43
Section 12.8 Determination of sample size
Approximately 75 subjects will be enrolled, which includes up to 2 cohorts of at least 40 subjects 
for Cohort 1 and at least 20 subjects for Cohort 2. No formal sample size calculation has been 
performed. The sample size was deemed clinically appropriate for the evaluation of safety, 
tolerability, and PK of iv LCM administration in pediatric subjects with epilepsy. 
Has been changed to:
Approximately 100 subjects will be enrolled, which includes up to 2 cohorts of at least 
40 subjects for Cohort 1 and approximately 44 subjects for Cohort 2. No formal sample size 
calculation has been performed. The sample size was deemed clinically appropriate for the 
evaluation of safety, tolerability, and PK of iv LCM administration in pediatric subjects with 
epilepsy. 
Change #44
Section 15 REFERENCES
Welsh SS, Lin N, Topjian AA, Abend NS. Safety of intravenous lacosamide in critically ill 
children. Seizure. 2017;52:76-80.
Has been added.
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 239 of 240
17
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
REDACTED COPY 
D
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Date/S
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UCB
30 Apr 2018
Clinical Study Protocol
Lacosamide
EP0060
Confidential
Page 240 of 240
18
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.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


Approval Signatures
Name:
EP0060-protocol-amend-3
Version:
2. 0
Document Number:
CLIN-000115394
Title:
EP0060 Protocol Amendment 3
Approved Date:
07 May 2018
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 04-May-2018 08:42:15 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 04-May-2018 17:49:43 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 07-May-2018 07:24:42 GMT+0000
DACTED 
REDA
DA
OPY
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App
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SAP_000.pdf: 
UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 1 of 66
STATISTICAL ANALYSIS PLAN 
Study: EP0060
Product: Lacosamide
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY AND
TOLERABILITY OF INTRAVENOUS LACOSAMIDE IN CHILDREN 
(≥1 MONTH TO <17 YEARS OF AGE) WITH EPILEPSY
SAP/Amendment Number
Date
Final SAP
11 August 2017
SAP Amendment 1
02 July 2018
SAP Amendment 2
21 June 2019
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.
REDACTED COPY 
This document cannot be used to
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 2 of 66
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................6 
1 
INTRODUCTION .............................................................................................................8 
2 
PROTOCOL SUMMARY.................................................................................................8 
2.1 
Study objectives.............................................................................................................8 
2.1.1 
Primary objective...................................................................................................8 
2.1.2 
Additional objective...............................................................................................8 
2.2 
Study variables...............................................................................................................8 
2.2.1 
Primary safety variables ........................................................................................8 
2.2.2 
Other safety variables ............................................................................................8 
2.2.3 
Other pharmacokinetic variables ...........................................................................8 
2.3 
Study design and conduct ..............................................................................................8 
2.4 
Determination of sample size.......................................................................................11 
3 
DATA ANALYSIS CONSIDERATIONS......................................................................11 
3.1 
General presentation of summaries and analyses ........................................................11 
3.2 
General study level definitions ....................................................................................12 
3.2.1 
Analysis time points ............................................................................................12 
3.2.1.1 
First and last dose of iv LCM....................................................................12 
3.2.1.2 
Relative day and time................................................................................12 
3.2.2 
Analysis periods...................................................................................................13 
3.2.3 
Study visit labeling ..............................................................................................13 
3.2.4 
Exposure duration................................................................................................14 
3.2.5 
Age and Age at first diagnosis.............................................................................14 
3.2.6 
Time since first epileptic seizure and last status epilepticus ...............................14 
3.2.7 
Body mass index (BMI).......................................................................................14 
3.3 
Definition of Baseline values.......................................................................................14 
3.4 
Protocol deviations.......................................................................................................15 
3.5 
Analysis sets.................................................................................................................15 
3.5.1 
Safety Set.............................................................................................................15 
3.5.2 
Safety Set iv.........................................................................................................15 
3.5.3 
Pharmacokinetic-Per Protocol Set .......................................................................15 
3.6 
Treatment assignment and treatment groups ...............................................................15 
3.7 
Center pooling strategy................................................................................................15 
3.8 
Coding dictionaries ......................................................................................................15 
3.9 
Changes to protocol-defined analyses .........................................................................15 
4 
STATISTICAL/ANALYTICAL ISSUES.......................................................................16 
4.1 
Adjustments for covariates ..........................................................................................16 
4.2 
Handling of dropouts or missing data..........................................................................16 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 3 of 66
4.2.1 
General imputation rule for incomplete dates .....................................................16 
4.2.2 
Handling of prior and concomitant medications with missing data ....................16 
4.2.3 
Handling of adverse events with missing data ....................................................17 
4.2.4 
Handling of study medication with missing data ................................................18 
4.2.5 
Handling of epilepsy diagnosis with missing data ..............................................18 
4.3 
Interim analyses and data monitoring..........................................................................18 
4.4 
Multicenter studies.......................................................................................................20 
4.5 
Multiple comparisons/multiplicity...............................................................................20 
4.6 
Use of an efficacy subset of study participants............................................................20 
4.7 
Active-control studies intended to show equivalence..................................................20 
4.8 
Examination of subgroups ...........................................................................................20 
5 
STUDY POPULATION CHARACTERISTICS.............................................................20 
5.1 
Study participant disposition........................................................................................20 
5.2 
Protocol deviations.......................................................................................................21 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................21 
6.1 
Demographics and other Baseline characteristics........................................................21 
6.2 
Medical history ............................................................................................................22 
6.3 
Potential Drug-Induced Liver Injury (PDILI)..............................................................22 
6.4 
History of epilepsy.......................................................................................................22 
6.4.1 
History of seizure types .......................................................................................22 
6.4.2 
History of seizure characteristics.........................................................................23 
6.4.3 
Historical seizure counts......................................................................................23 
6.5 
Prior and concomitant medications..............................................................................23 
6.5.1 
Concomitant Non-AEDs......................................................................................23 
6.5.2 
Concomitant AEDs..............................................................................................23 
6.6 
VNS setting and ketogenic diet....................................................................................23 
6.7 
Medical procedures......................................................................................................24 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................24 
8 
SAFETY ANALYSES.....................................................................................................24 
8.1 
Extent of exposure .......................................................................................................24 
8.2 
Adverse events.............................................................................................................24 
8.3 
Clinical laboratory evaluations ....................................................................................26 
8.4 
Vital signs, physical findings, and other observations related to safety......................27 
8.4.1 
Vital signs ............................................................................................................27 
8.4.2 
Electrocardiograms (ECGs).................................................................................29 
8.4.3 
Complete physical examination...........................................................................31 
8.4.4 
Complete neurological examination....................................................................31 
8.4.5 
Assessment of suicidality ....................................................................................31 
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21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 4 of 66
9 
PHARMACOKINETICS AND PHARMACODYNAMICS ..........................................31 
9.1 
Pharmacokinetics .........................................................................................................31 
9.1.1 
Pharmacokinetics Analysis..................................................................................32 
9.2 
Pharmacodynamics ......................................................................................................32 
10 EFFICACY ANALYSES ................................................................................................32 
11 REFERENCES ................................................................................................................33 
12 APPENDICES .................................................................................................................34 
12.1 
List of Other significant AEs of VIMPAT ..................................................................34 
12.2 
Marked abnormality criteria for laboratory data..........................................................37 
12.2.1 
Hematology..........................................................................................................37 
12.2.2 
Chemistry.............................................................................................................38 
12.2.3 
Required Investigations and follow up for PDILI ...............................................43 
12.2.4 
PDILI laboratory measurements..........................................................................44 
12.3     Additional PDILI information .....................................................................................46 
12.4     List of MedDRA Preferred Term for PDILI................................................................47 
13 AMENDMENTS TO THE STATISTICAL ANALYSIS PLAN....................................50 
13.1 
AMENDMENT 1.........................................................................................................50 
13.2 
AMENDMENT 2.........................................................................................................65 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE.....................................................66 
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21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 5 of 66
LIST OF TABLES
Table 8‒1: Vital signs abnormality criteria.........................................................................28 
Table 8‒2: ECG abnormality criteria..................................................................................29 
REDACTED COPY 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 6 of 66
LIST OF ABBREVIATIONS
AE
adverse event
AED
antiepileptic drug
AV
Atrioventricular
bid
twice daily
BP
Blood pressure
CRF
case report form
C-SSRS
Columbia-Suicide Severity Rating Scale
CV
coefficient of variation
DBP
diastolic blood pressure
DILI
drug-induced liver injury
DMC
Data Monitoring Committee
ECG
electrocardiogram 
eCRF
electronic Case Report Form
EMU
epilepsy monitoring unit
ETV
Early Termination Visit
iv
Intravenous
ILAE
International League Against Epilepsy
IIL
Initiating intravenous lacosamide Group
LCM
lacosamide
LOQ
limit of quantification
MA
markedly abnormal
MedDRA
Medical Dictionary for Regulatory Activities
OLL
Open-label lacosamide Group
PDILI
potential drug-induced liver injury
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 7 of 66
PK
pharmacokinetic(s)
PK-PPS
Pharmacokinetic Per Protocol Set
PT
preferred term
RxL
Prescription lacosamide (eg, VIMPAT) Group
SAP
Statistical Analysis Plan
SBP
systolic blood pressure
SD
standard deviation
SOC
system organ class
SS
Safety Set
SS-iv
Safety Set iv
TEAE
treatment-emergent adverse event
TEMA
treatment-emergent marked abnormalities
ULN
upper limit of normal
VNS
vagus nerve stimulation
WHODD
World Health Organization Drug Dictionary
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21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 8 of 66
1
INTRODUCTION
This Statistical Analysis Plan (SAP) defines the scope of statistical analyses and provides a 
detailed description of statistical methodology for the statistical analyses to support the final 
clinical study report for EP0060. This SAP is based upon the following documents: (Final 
Protocol: 16Dec2014, Protocol Amendment 1: 21Jul2015, Protocol Amendment 2: 30Nov2016,
Protocol Amendment 3: 30Apr2018).
2
PROTOCOL SUMMARY
2.1
Study objectives
2.1.1
Primary objective
The primary objective of the study is to evaluate the safety and tolerability of intravenous (iv)
Lacosamide (LCM) infusion(s) in pediatric study participants ≥1 month to <17 years with 
epilepsy.
2.1.2
Additional objective
An additional objective of the study is to evaluate the pharmacokinetics (PK) of iv LCM in 
pediatric study participants with epilepsy.
2.2
Study variables
2.2.1
Primary safety variables
Safety and tolerability will be assessed using the following primary variables:
x
Adverse events (AEs) reported spontaneously by the study participant and/or caregiver 
(including parent/legal guardian) or observed by the investigator
x
Study participant withdrawals due to AEs
2.2.2
Other safety variables
Other safety variables include the following:
x
Changes in 12-lead electrocardiogram (ECGs)
x
Changes in vital sign measurements (blood pressure [BP] and pulse rate)
x
Changes in physical examinations
x
Changes in neurological examinations
2.2.3
Other pharmacokinetic variables
The other PK variables will include plasma concentration of LCM and its main metabolite, 
SPM 12809.
2.3
Study design and conduct
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of iv
LCM infusions in pediatric study participants ≥1 month to <17 years of age with epilepsy. Based 
on a local protocol amendment only patients between ≥1 month to <16 years of age will be 
enrolled in Ukraine. The study will include approximately 100 study participants.
The following patients will be eligible for enrollment in EP0060:
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 9 of 66
x
Open-label LCM (OLL) patients: currently receiving oral LCM as adjunctive or 
monotherapy as participants in an open-label long-term study (SP848, EP0034, or other 
pediatric study).
x
Prescribed-LCM (RxL) patients: currently receiving prescribed oral LCM from commercial 
supply (eg, VIMPAT) as adjunctive or monotherapy
x
Initiating iv LCM (IIL) patients: not currently receiving LCM and will receive iv LCM as 
adjunctive treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL study 
participants.
Study participants can receive iv LCM as follows:
x
Replacement for oral LCM treatment (OLL and RxL study participants):
-
Clinical need administration: study participants currently taking prescribed oral LCM (or 
any enteric LCM administration, eg, LCM administration by feeding tube) who need to 
undergo a procedure and are treated at an epilepsy monitoring unit (EMU) or health care 
facility, or other situations where iv administration is clinically appropriate and oral 
administration is not feasible (ie, surgery). In these study participants, the maximum 
number of iv doses of LCM is 10.
-
Elective administration: study participants currently taking oral LCM (or any enteric
LCM administration, eg, LCM administration by feeding tube) who elect to receive iv
LCM administration at an EMU or healthcare facility. In these study participants, the 
maximum number of iv doses of LCM is 2.
x
Adjunctive iv LCM treatment initiation (IIL study participants):
-
Clinical need administration: study participants not currently taking LCM who need to 
undergo a procedure, be treated at an EMU or health care facility, or other situations 
where iv administration is clinically appropriate and oral administration is not feasible 
(ie, surgery). In these study participants, the maximum number of iv doses of LCM is 10. 
-
Elective administration: study participants not currently taking LCM and elect to initiate 
adjunctive treatment using iv LCM in a healthcare facility. In these study participants, the 
maximum number of iv doses of LCM is 2.
EP0060 is composed of the following study periods:
x
For all study participants:
-
Screening and/or Baseline Period (up to 7 days),
-
Treatment Period
(1) Clinical need administration: up to 10 doses or up to 5 days (iv LCM will be 
administered bid at approximately 12-hour intervals, once in the morning and 
once in the evening, for up to 10 doses or up to 5 days).
(2) Elective administration: up to 2 consecutive doses over approximately 24 hours
-
End-of-Study/Final Visit (1 day),
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 10 of 66
-
End-of-Study/Telephone Contact 1 (1 to 3 days),
x
Additional visits or contacts as follows:
-
RxL and IIL study participants who are eligible and choose to continue oral LCM for 
up to 2 years in SP848
o
Transition Visit, which can be concurrent with Final Visit or separate (up to 
7 days after Final Visit)
-
RxL and IIL study participants who do not continue LCM treatment in SP848
o
End-of-Study/Telephone Contact 2 (30 days [±2 days] after last iv infusion of 
study LCM).
The maximum study durations are as follows:
x
Approximately 16 days:
-
Study participants in the OLL group will resume participation in their respective 
study and either resume oral LCM treatment or follow taper regimen as described in
the long-term, open-label study accordingly.
x
Approximately 23 days:
-
Study participants in the RxL or IIL groups who, if determined clinically appropriate, 
are given the option to continue oral LCM treatment in SP848.
x
Approximately 45 days:
-
Study participants in the RxL or IIL groups who will not continue oral LCM 
treatment in SP848.
EP0060 is planned to include up to 2 age-based cohorts and will begin with Cohort 1, including 
at least 40 study participants ≥8 to <17 years of age. Within Cohort 1, at least 20 study 
participants will be ≥12 to <17 years of age and at least 20 study participants will be ≥8 to <12 
years of age. For the first 20 study participants in Cohort 1, iv LCM should be infused over a 
duration of 30 minutes but not longer than 60 minutes whenever possible.
The Data Monitoring Committee (DMC) will review the safety and tolerability data from the
first 20 study participants completed in Cohort 1. Based on this review, the DMC will make 
recommendations as follows:
x
EITHER approximately 30 additional study participants will be enrolled in Cohort 1 with 
target infusion duration of 15 minutes but no longer than 30 minutes only in study 
participants who would directly benefit from an increased infusion rate, in the opinion of the 
Investigator. Study participants who will not directly benefit from a 15 to 30 minute infusion
duration, in the opinion of the Investigator, cannot receive the faster infusion. These study 
participants should receive an infusion of 30 minutes but not longer than 60 minutes,
x
OR approximately 30 additional study participants will be enrolled in Cohort 1 with a target 
infusion duration of 30 minutes but not longer than 60 minutes,
x
OR study should be stopped,
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 11 of 66
x
AND whether Cohort 2 can be initiated.
For Cohort 2, approximately 44 study participants ≥1 month to <8 years of age will be enrolled 
to receive iv LCM. For the first 20 study participants in Cohort 2, iv LCM should be infused over 
a duration of 30 minutes but not longer than 60 minutes whenever possible. 
After completion of the first 20 study participants in Cohort 2, the DMC will review the 
available safety and tolerability data from Cohort 1 and Cohort 2. Based on this review, the 
DMC will make recommendations as follows:
x
EITHER approximately 30 additional study participants will be enrolled in Cohort 2 with a 
target infusion duration of 15 minutes but not longer than 30 minutes only in study 
participants who would directly benefit from an increased infusion rate, in the opinion of the 
Investigator. Study participants who will not directly benefit from a 15 to 30 minute infusion, 
in the opinion of the Investigator, cannot receive the faster infusion. These study participants
should receive an infusion of 30 minutes but no longer than 60 minutes,
x
OR approximately 30 additional study participants will be enrolled in Cohort 2 with a target 
infusion duration of 30 minutes but not longer than 60 minutes,
x
OR Cohort 2 should be stopped.
The design will result in a total exposure of approximately 100 pediatric study participants to 
assess the safety and tolerability of iv LCM over a range of infusion durations. A completer for 
this study is defined as a study participant who completes at least 1 visit with iv LCM treatment 
and the associated assessments for that visit (eg, PK samples, vital signs, 12-lead ECG). The 
study participant should have ‘Completed study participant’ selected as a status at termination.
2.4
Determination of sample size
Approximately 100 study participants will be enrolled, which includes up to 2 cohorts of at least 
40 study participants for Cohort 1 and approximately 44 study participants for Cohort 2. No 
formal sample size calculation has been performed. The sample size was deemed clinically 
appropriate for the evaluation of safety, tolerability, and PK of iv LCM administration in 
pediatric study participants with epilepsy.
The following cohorts are planned:
x
Cohort 1: at least 40 study participants from ≥8 to <17 years of age, with at least 20 study 
participants from ≥12 to <17 years of age and at least 20 study participants from ≥8 to <12 
years of age
x
Cohort 2: approximately 44 study participants from ≥1 month to <8 years of age; every 
attempt will be made to enroll 20 study participants ≥4 to <8 years of age, 12 study 
participants ≥2 to <4 years of age, and 12 study participants ≥1 month to <2 years of age
The remaining study participants may be enrolled in either of the 2 age cohorts.
3
DATA ANALYSIS CONSIDERATIONS
3.1
General presentation of summaries and analyses
Statistical analysis and generation of tables, figures, study participant data listings, and statistical 
outputs will be performed using SAS Version 9.1 or higher. All summaries will be descriptive; 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 12 of 66
no statistical hypothesis testing is planned. All tables and listings will use Courier New font size 
9.
For categorical parameters, the number and percentage of study participants in each category will 
be presented. The denominator for percentages will be based on the number of study participants
appropriate for the purpose of the analysis. Unless otherwise noted, all percentages will be 
displayed to 1 decimal place. No percentage will be displayed for zero counts, and no decimal 
will be presented when the percentage is 100%. For continuous parameters, descriptive statistics 
will include number of study participants (n), mean, standard deviation (SD), median, minimum, 
and maximum, unless otherwise stated. For PK parameters, the coefficient of variation (CV) and 
geometric mean may also be presented.
Decimal places for descriptive statistics will always apply the following rules:
x
“n” will be an integer
x
Mean, SD, and median will use 1 additional decimal place compared to the original data
x
CV[%] will be presented with 1 decimal place
x
Minimum and maximum will have the same number of decimal places as the original value
However, the maximum number of decimals displayed will not exceed 4.
All summaries, unless otherwise stated, will be presented overall for all study participants and by 
age cohorts (≥1 month to <8 years and ≥8 to <17). Selected tables will be provided in addition 
by study participant groups (OLL and RxL, combined, and IIL) and target infusion duration (15-
30 minutes, and 30-60 minutes).
A complete set of listings containing all documented data and relevant derived data (eg, change 
from Baseline) will be generated.
3.2
General study level definitions
3.2.1
Analysis time points
3.2.1.1
First and last dose of iv LCM
Unless otherwise noted, all references to the first dose of iv LCM in this SAP refer to the first 
dose of iv LCM during EP0060. Unless otherwise noted, all references to the last dose of iv
LCM in this SAP refer to the last dose of iv LCM in this study.
3.2.1.2
Relative day and time
Relative Day is defined as the day relative to the first infusion of study drug.
If the current date occurred on or after the day of first dose of iv LCM and prior to or on the day 
of last iv LCM dose, the relative day will be calculated as the current date minus the date of first 
dose of iv LCM plus 1 (eg, the day of first dose will be Day 1).
If the current date occurred prior to the first dose of iv LCM, the relative day will be calculated
as date of first dose of iv LCM minus the current date (eg, the day prior to first dose will be 
Day -1).
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 13 of 66
If the current date occurred after the last dose of iv LCM, the relative day will be calculated as 
the current date minus the date of last dose of iv LCM including a “+” to denote post-treatment 
days (eg, the day after the last dose will be Day +1). 
Relative day will not be calculated for partial dates.
Time will also be collected to ascertain if the event/sample/collection was before or after the first
iv LCM even if it happened on the same day.
In order to have a better insight into the times of AEs, concomitant antiepileptic drugs (AED),
laboratory samples, ECG and vital signs collections relative to the administration of study 
medication, the relative time will be displayed in hours and minutes for relative times ≤24 hours 
before and after first iv LCM administration. For relative times >24 hours the relative times will 
be displayed in days as described above.
3.2.2
Analysis periods
This study consists of a Screening and/or Baseline Period, an iv Treatment Period and a Post-iv
Treatment Period.
Screening and/or Baseline Period
This is defined as the period of time from Day -7 to Day 1 prior to the iv LCM first dose which 
means that the first visit can occur before or on the same day as the first iv LCM infusion.
iv Treatment Period
Treatment days are as follows:
(1) Clinical need administration: up to 10 doses or up to 5 days
(2) Elective administration: up to 2 consecutive doses over approximately 24 hours
The iv Treatment Period is defined as the period of time from the iv LCM first dose date and 
time to the iv LCM last dose date and time, inclusive.
Post-iv Treatment Period
This is defined as the period of time after the end date and time of the iv Treatment Period to the 
last contact with the study participant.
Listings will also include “Unscheduled Visit” as applicable.
3.2.3
Study visit labeling
Visits will be labeled in table summaries (according to the schedule outlined in Section 5.2 of the 
protocol) as follows:
x
“Visit X (Descriptor)” for scheduled visits during the Screening/Baseline Period
x
“Visit X” for scheduled visits during the iv Treatment Period
x
“Final Visit”
x
“Telephone Contact 1”
x
“Telephone Contact 2”
x
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 14 of 66
3.2.4
Exposure duration
Exposure duration refers to the first and last dose of iv LCM. The date of first infusion of study 
medication is defined as the first study medication infusion date according to the standard case 
report form (CRF) page.
The date of last infusion of study medication is defined as the last infusion of study medication 
reported on the standard trial termination CRF. 
The number of days of exposure is defined as the treatment stop date minus the treatment start 
date +1 day. Days with unknown or zero dosing which occur prior to the last infusion of study 
medication in the study should be included in the calculation.
3.2.5
Age and Age at first diagnosis
Age will be given in years and will be derived applying the rules for missing data imputation
(see Section 4.2.1 and the SDTM derivation definition). The age at first diagnosis will be given 
in years and will be derived applying all rules for missing data imputation (see Section 4.2.1)
with the following formulas:
Missing or partial epilepsy diagnosis date will be derived applying all rules for missing data 
imputation (see Section 4.2.1) and age at first diagnosis will use the following formulas, where 
applicable.
The following formula will be applied where birthdate is a complete date: 
(Date of first diagnosis of epilepsy – Date of birth) / 365.25
The following formula will be applied where birthdate is a partial date:
(Enrollment age in years) – [(Informed consent date – Epilepsy diagnosis date) / 365.25], if the 
value is negative then age at diagnosis will be set to zero.
3.2.6
Time since first epileptic seizure and last status epilepticus
Time since first epileptic seizure and time since last status epilepticus will be given in years and 
will be derived applying all rules for missing date imputation (see Section 4.2.1) with the 
following formula (respectively): 
(Date of informed consent - Date of first epileptic seizure) / 365.25 
(Date of informed consent - Date of last status epilepticus) / 365.25
3.2.7
Body mass index (BMI)
BMI will be calculated using the formula:
BMI = weight (kg) / (height (m))2
3.3
Definition of Baseline values
Baseline for laboratory variables (blood chemistry, hematology), vital signs, body weight, and 
quantitative electrocardiography (ECG) variables is defined as the last value prior to the first 
infusion of study drug (pre-iv LCM measurement). Individual laboratory variables should all 
come from the same timepoint. Same applies to the individual vital sign variables, except for 
weight. Both scheduled and unscheduled assessments from the central laboratory are considered.
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 15 of 66
3.4
Protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on the primary outcomes for an individual study participant. The criteria for 
identifying important protocol deviations will be defined within the appropriate protocol-specific 
document. Important protocol deviations will be reviewed as part of the ongoing data cleaning 
process and data evaluation. Important deviations will be identified and documented prior to 
database lock to confirm exclusion from analysis sets.
3.5
Analysis sets
3.5.1
Safety Set
The Safety Set (SS) will include study participants who received at least 1 dose of EP0060 study 
drug LCM (oral and/or iv). Selected safety summaries will be presented for the SS. If the SS and 
the SS-iv consist of the same number of study participants, tables will only be presented for the 
SS-iv.
3.5.2
Safety Set iv
The Safety Set iv (SS-iv) will include study participants in the SS who received at least 1 dose of 
EP0060 study drug iv LCM. The SS-iv will be the primary analysis set for the analysis of safety 
data.
3.5.3
Pharmacokinetic-Per Protocol Set 
The Pharmacokinetic-Per Protocol Set (PK-PPS) will include all study participants in the SS-iv
having provided at least 1 measurable post-dose plasma sample (with recorded sampling time) 
on at least 1 study day with documented iv LCM intake times and without important protocol 
deviations impacting the interpretability of the PK analysis.
3.6
Treatment assignment and treatment groups
This is an open-label study with a single treatment arm. Study participants are summarized based 
on the age-based cohorts defined as:
•
≥8 to <17 years (Age Cohort 1)
•
≥1 month to <8 years (Age Cohort 2)
3.7
Center pooling strategy
No pooling of centers is planned for this study. 
3.8
Coding dictionaries
Medical history and AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) version 16.1. Medications will be coded using the World Health Organization Drug 
Reference List (WHODD SEP/2013). Medical procedures will not be coded.
3.9
Changes to protocol-defined analyses
There are no changes to analyses specified in the protocol.
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 16 of 66
4
STATISTICAL/ANALYTICAL ISSUES
4.1
Adjustments for covariates
No statistical testing is planned; therefore, this section is not applicable for this study.
4.2
Handling of dropouts or missing data
No imputation of missing values for analysis parameters is planned unless otherwise noted. 
Imputations for missing or partial values for dates for AEs and concomitant medications will be 
applied to determine if an event is to be considered treatment-emergent or concomitant. Across 
safety and PK analysis, only reported data will be used. 
4.2.1
General imputation rule for incomplete dates
Where necessary for the calculation of derived variables, partial dates will be completed using 
the earliest calendar date based on the partial date provided. This rule is valid for all partial dates 
with the exception of the following:
x
Start and stop dates of concomitant medication
x
Start and stop date of adverse events
x
Start and stop dates of study medication
x
Date of epilepsy diagnosis
Completely missing dates will not be replaced and the corresponding derived variables will be 
set to missing.
4.2.2
Handling of prior and concomitant medications with missing data
Any medications with incomplete start and end dates will be handled according to the following 
rules for classification as prior and concomitant and for the calculation of relative study days.
Such imputations will only be performed for these classifications and calculations; in the listings 
all data will be shown as recorded on the electronic case report form (eCRF).
Imputation of Partial Start Dates
x
If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date, then use the 1st of the month.
x
If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start, then use the date of first dose.
x
If only the year is specified, and the year of first dose is not the same as the year of the start 
date, then use January 1 of the year of the start date.
x
If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose.
x
If the start date is completely unknown and the stop date is unknown or not prior to the date 
of first dose, then use the date of first dose.
Imputation of Partial Stop Dates
x
If only the month and year are specified, then use the last day of the month.
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 17 of 66
x
If only the year is specified, then use December 31 of that year.
x
If the stop date is completely unknown, do not impute the stop date.
In the event of ambiguity or incomplete data which makes it impossible to determine whether a 
medication was concomitant or not, the medication will be considered as concomitant.
4.2.3
Handling of adverse events with missing data
Any AEs with incomplete onset and outcome (end) dates/times will be handled according to the 
following rules for classification as treatment-emergent. Such imputations will only be 
performed for these classifications; in the listings all data will be shown as recorded on the 
eCRF. 
Imputation of Partial Onset Dates
x
If only the month and year are specified and the month and year of first dose of iv LCM is
not the same as the month and year of onset, then use the 1st of the month.
x
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the same as the month and year of onset, then use the date/time of first dose of iv LCM.
x
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of onset, then use January 1 of the year of onset.
x
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onset, then use the date/time of first dose.
x
If the AE onset date is completely unknown, then use the date of first dose of iv LCM.
x
If the onset time of the event is unknown, impute it as 00:00 unless the known part of the 
onset date is the same as the date of first iv LCM dose; in this case impute the time of first 
dose of iv LCM dose.
Imputation of Partial End Dates
x
If only the month and year are specified, then use the last day of the month.
x
If only the year is specified, then use December 31 of that year.
x
If the AE resolved and the resolution date is completely unknown, then do not impute the 
resolution date.
With respect to AEs, events with missing intensity will be assumed to be severe. Events with 
missing relationship to iv LCM per the investigator will be assumed to be related.
Data handling for worsened AEs is provided below. The standard AE CRF has the outcome of 
“worsened” to be used when there is an increase in the intensity of an AE. The definition of 
“worsened” is when the AE is still present but at a heightened intensity. CRF instructions dictate 
to complete a new AE screen with the event term of the worsened event.  
Note that the outcome of “worsened” is not allowed terminology within the CDISC standards. In 
the SDTM.AE, the data is mapped to the outcome “Not Recovered/Not Resolved”. The outcome 
of “Worsened” will be kept in SDTM.SUPPAE. For study participant data listings, the 
convention will be to use the mapped SDTM terminology of “Not Recovered/Not Resolved”.
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21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 18 of 66
4.2.4
Handling of study medication with missing data
No imputation should be performed for missing study medication start dates. This field on the 
CRF should not be partial or missing.
For partial or missing date of last dose of study medication, the following imputation rules will 
be applied for the purpose of calculating overall exposure:
x
If the day is missing (but month and year available), impute the last dose date as the 
minimum of the last day of the month or the date of last contact reported on the trial 
termination CRF; if day and month are both missing (only year available), impute the last 
dose date as the minimum of the last day of the year or the date of last contact on the trial 
termination CRF.
x
If a study participant died and has a partial or missing last administration date, the date is to 
set to the date of death. If there is a partial date of last dose and the month/year are prior to 
the month and year of the date of death, follow partial date imputation rules.
x
If the last dose date is completely missing and no information could be obtained from data 
cleaning exercises, the last dose date should be imputed as the date of last contact according 
to the study termination CRF. A review of the data for study participants with completely 
missing last dose dates should be performed to ensure that the imputation does not result in 
an unrealistic value for duration of exposure. 
x
Imputed date of last dose dates should only be used for calculation of the duration of 
exposure. The date as recorded on the CRF should be presented in study participant data 
listings (no imputed dates should be included in study participant data listings).
4.2.5
Handling of epilepsy diagnosis with missing data
Imputation methods should be applied for missing or partial epilepsy diagnosis date. 
x
If the month and year are available, the diagnosis date is imputed as the later of the 
following dates: the first day of the month, the study participant’s birthdate, or the date of 
the first seizure (if available).
x
If only a year is available, the later of the following dates will be imputed: January 1st of
the year, the study participant’s birthdate, and the date of the first seizure.
x
Completely missing dates will not be replaced and the corresponding derived variables 
will be set to missing.
4.3
Interim analyses and data monitoring
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of the first 20 study participants in Cohort 1 and after 
completion of the first 20 study participants in Cohort 2.
No formal stopping rule will be applied. The DMC may give a recommendation to stop the study 
after reviewing the safety data as described below. A recommendation for stopping should be 
based on the collective experience of the DMC members. After meeting to review data from each 
cohort, the DMC will provide a recommendation in writing regarding whether to continue or to 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 19 of 66
stop the study. UCB will consider this recommendation and ensure the study investigators are 
informed of the sponsor’s decision on how to continue as described below.
The DMC members will be defined in the DMC charter. 
EP0060 will begin with Cohort 1, where at least 40 study participants ≥8 to <17 years of age will 
be enrolled to receive iv LCM. Within Cohort 1, at least 20 study participants will be ≥12 to <17 
years of age and at least 20 study participants will be ≥8 to <12 years of age. For the first 20
study participants in Cohort 1, iv LCM should be infused over a duration of 30 minutes but not
longer than 60 minutes whenever possible.
After completion of the first 20 study participants in Cohort 1, the DMC will review the safety 
and tolerability data from these study participants. Based on this review, the DMC will make 
recommendations as follows:
x
EITHER approximately 30 additional study participants will be enrolled in Cohort 1 with 
target infusion durations as follows:
-
15 minutes but not longer than 30 minutes only in study participants who would 
directly benefit from an increased infusion rate, in the opinion of the Investigator; 
OR,
-
30 minutes but not longer than 60 minutes in study participants who would not 
directly benefit from an increased infusion rate, in the opinion of the Investigator
x
OR approximately 30 additional study participants will be enrolled in Cohort 1 with a target 
infusion duration of 30 minutes but not longer than 60 minutes,
x
OR study should be stopped,
x
AND whether Cohort 2 can be initiated.
For Cohort 2, approximately 44 study participants ≥1 month to <8 years of age will be enrolled 
to receive iv LCM. For the first 20 study participants in Cohort 2, iv LCM should be infused over 
a duration of 30 minutes but no longer than 60 minutes whenever possible.
After completion of the first 20 study participants in Cohort 2, the DMC will review the 
available safety and tolerability data from Cohort 1 and Cohort 2. Based on this review, the 
DMC will make recommendations as follows: 
x
EITHER approximately 30 additional study participants will be enrolled in Cohort 2 with
target infusion durations as follows:
-
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directly benefit from an increased infusion rate, in the opinion of the Investigator; 
OR,
-
30 minutes but not longer than 60 minutes in study participants who would not 
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x
OR approximately 30 additional study participants will be enrolled in Cohort 2 with target 
infusion duration of 30 minutes but not longer than 60 minutes, 
x
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21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 20 of 66
4.4
Multicenter studies
No multicenter analysis is planned therefore this section is not applicable for this study. 
4.5
Multiple comparisons/multiplicity
No statistical testing is planned; therefore, this section is not applicable for this study.
4.6
Use of an efficacy subset of study participants
No efficacy data are collected; therefore, this section is not applicable for this study.
4.7
Active-control studies intended to show equivalence
This section is not applicable for this study.
4.8
Examination of subgroups
For analyses, the study participant groups and the target infusion duration groups will be
combined to create a 4-level subgroup:
x
OLL and RxL study participants/15 – 30 minutes
x
OLL and RxL study participants/30 – 60 minutes
x
IIL study participants/15 – 30 minutes
x
IIL study participants/30 – 60 minutes
5
STUDY POPULATION CHARACTERISTICS
5.1
Study participant disposition
Study participants who were screen failures, broken down by primary reason for screening 
failure will be presented overall for all study participants screened.
A summary of disposition of study participants will be provided for all screened study 
participants. The date of first study participant in (date of first Screening visit), date of last study 
participant out (date of last visit (in clinic) for last study participant), number of study 
participants screened, and the number of study participants in each analysis set (SS-iv, SS and
PK-PPS) will be summarized overall, by country and by investigator site. Study participants who 
transferred sites will be summarized according to their original site. 
A summary of disposition of analysis sets will be provided for all study participants screened:
x
The number and percentage of study participants in the SS-iv
x
The number and percentage of study participants in the SS
x
The number and percentage of study participants in the PK-PPS
A summary of disposition and discontinuation reasons will be presented for all study participants
in the SS-iv and the SS. The summary will be presented by age cohort, all study participants and 
by subgroup. The following information is included:
x
The number and percentage of study participants starting the study
x
The number and percentage of study participants completing the study 
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21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 21 of 66
x
The overall number and percentage of study participants discontinuing and the number 
and percentage of study participants discontinuing by primary reason for discontinuation
A summary of discontinuations due to AEs for the SS-iv will present the number and percentage 
of study participants who discontinued this study due to AEs broken down by type of AE. The 
table will be presented by age cohort, all study participants and by subgroup and will be repeated 
for the SS.
The following listings will be provided: study participants who did not meet study eligibility 
criteria, study participant disposition, study discontinuation, study participant analysis sets, study 
participants excluded from at least one analysis set, visit dates, and study participant number.
5.2
Protocol deviations
Important protocol deviations defined in the protocol-specific document, and additionally 
identified at the data evaluation meetings, will be listed. In addition, the number and percentage 
of study participants with at least one important protocol deviation will be summarized overall 
and by category of important protocol deviation for the SS-iv and the SS. The number and 
percentage of study participants with no important protocol deviations will also be summarized.
6
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS
6.1
Demographics and other Baseline characteristics
Demographic variables will be presented for the SS-iv and the SS. The variables to be considered 
are:
x
Age at entry into EP0060 
x
Categorized age:
o
EudraCT age categories: >=1 month to < 2 years, >=2 to <12 years and >=12 to
<17 years 
o
Age cohort categories: >=1 month to < 2 years, >=2 to <4 years, >=4 to <8 years, 
>=8 to <12 years and >=12 to <17 year
x
Gender
x
Study participant group (OLL, RxL, and IIL)
x
Target infusion duration (15-30 minutes and 30-60 minutes)
x
Subgroup: (OLL/15 – 30 minutes, OLL/30 – 60 minutes, RxL/15 – 30 minutes, RxL/30 –
60 minutes, IIL/15 – 30 minutes, IIL/30 – 60 minutes)
x
Weight (kg)
o
Categorized weight: 0 to <30kg, 30 to <50kg, >=50kg
x
Height (cm)
x
BMI (kg/m2) (as defined in Section 3.2.7 )
x
Racial group (American Indian/Alaskan Native, Asian, Black, Native Hawaiian or Other 
Pacific Islander, White, and Other/Mixed)
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 22 of 66
x
Ethnicity (Hispanic or Latino or Not Hispanic or Latino)
x
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x
Vagus nerve stimulation (VNS) use (Active VNS, No VNS, and VNS not active)
Listings of demographics, VNS at screening and childbearing potential will be provided.
6.2
Medical history 
Medical history for RxL and IIL will be obtained from the Screening Visit Medical History 
eCRF module in EP0060. Medical History for OLL study participants will come from their 
medical history from their respective previous study.
The number and percentage of study participants with a medical history condition (except 
epilepsy), including both resolved and ongoing conditions, will be summarized by MedDRA 
primary system organ class (SOC) and preferred term (PT) for the SS-iv. Previous and ongoing 
medical history glossary and previous and ongoing medical history conditions listings (except 
epilepsy) will be provided. 
6.3
Potential Drug-Induced Liver Injury (PDILI)
Where applicable, potential drug induced liver injury will be captured as described in
Section 12.2.4 and DILI information will be listed (see Section 8.3).
6.4
History of epilepsy
6.4.1
History of seizure types
The number and percentage of study participants experiencing partial-onset seizures (type I), 
simple partial (type IA), complex partial (type IB), partial, secondary generalized (type IC), 
generalized  (type II), absence (IIA), myoclonic (IIB), clonic (IIC), tonic (IID), tonic-clonic 
(IIE), and atonic (IIF) seizures during 4 weeks prior to the screening visit for EP0060 will be
summarized for the SS-iv based on the International League Against Epilepsy (ILAE) Seizure 
Classification Historical Seizure Count eCRF module.
A study participant will be classified as having a history of partial-onset seizures (I) if the study 
participant has a history of simple partial (IA), complex partial (IB), or partial evolving to
secondary generalized (IC) seizures. A study participant will be classified as having a history of 
generalized seizures (II) if the study participant has a history of primary generalized with an 
unknown subtype (II), absence (IIA), myoclonic (IIB), clonic (IIC), tonic (IID), tonic-clonic 
(IIE), or atonic (IIF) seizures. A study participant may also be classified as having a history of 
unclassified epileptic seizures (III).
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 23 of 66
6.4.2
History of seizure characteristics
History of withdrawal seizures, history of status epilepticus, age at first diagnosis (as defined in 
Section 3.2.5), time since first epileptic seizure (as defined in Section 3.2.6), and time since last 
status epilepticus (as defined in Section 3.2.6) will be summarized and listed where available.
For direct enrollers, this information will be collected in the History of Epileptic Seizures eCRF 
for EP0060. For OLL study participants this information will come from their previous study.
6.4.3
Historical seizure counts
The Historical Seizure Count eCRF module records the number of seizures per pre-selected 
ILAE seizure code experienced by the study participant during the 4 weeks prior to the 
Screening Visit. These data will be provided in a study participant data listing. For OLL study 
participants this information will come from their previous study.
6.5
Prior and concomitant medications
Prior medications include any medications that started prior to the date of first dose of LCM 
study drug. Concomitant medications are medications taken at least one day in common with 
study drug LCM in EP0060. Medications may be both prior and concomitant.
For OLL study participants only concomitant medication which started during the EP0060 study 
will be recorded in the EP0060 study. Information of medication which started before EP0060 
study start will come from the respective OLL study. Prior AEDs will be defined by a manual 
medical review of all unique combinations of ATC codes and indications reported in the 
database to identify prior medications taken to treat epilepsy.
Medications will be listed as follows: prior and concomitant non-AEDs, glossary of non-AEDs 
with verbatim term coded into ATC levels 1 and 2, prior and concomitant AEDs, and glossary of 
AEDs with verbatim term coded into ATC level 4.
Handling of prior and concomitant medications missing data is described in the Section 4.2.2.
6.5.1
Concomitant Non-AEDs
Non-AEDs taken at least one day in common with LCM study drug in EP0060 will be 
considered as concomitant medications. Medications will be summarized by ATC Code level 1
and 2 for the SS-iv. Study participants reporting multiple medications within an ATC class are 
counted once per medication and class. 
6.5.2
Concomitant AEDs
Concomitant AEDs are defined as AEDs taken concomitantly for at least one day in common 
with LCM study drug in EP0060. AEDs are reported on the Concomitant Medications (AEDs 
only) eCRF page. Concomitant AEDs will be summarized by Level 4 ATC code and generic 
medication name. If a medication identified as an AED does not code to a level 4 ATC code, the 
highest level of coding will be displayed along with the generic medication name. Summaries of 
AEDs will be presented separately from other concomitant medications for the SS-iv population.
6.6
VNS setting and ketogenic diet
Two separate listings for Vagus Nerve Stimulation Status at Screening and since last visit will be 
provided.
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 24 of 66
Ketogenic diets data reported on Special Diets eCRF will be presented in a study participant
listing.
6.7
Medical procedures
Concomitant medical procedures per study participant will be listed.
In addition, a listing of procedure history for study participants who had any procedures or 
surgeries prior to study entry will be provided.
For RxL and IIL study participants, procedure history will be obtained from the Procedure 
History eCRF. For OLL study participants, procedures with stop dates prior to the date of first 
dose of iv LCM in EP0060, procedure history will be obtained from the respective OLL 
Concomitant Procedure eCRF.
7
MEASUREMENTS OF TREATMENT COMPLIANCE
Information reported on the eCRF Drug Accountability (iv formulation) will be listed. The data 
from the eCRF Drug Accountability (Oral solution) will also be listed. No summaries of these 
results are planned.
LCM dosing compliance will be evaluated through the review of important protocol deviations.
8
SAFETY ANALYSES
All analyses for extent of exposure and safety are performed for the SS-iv.  
Inferential statistical tests are not planned for the safety variables.
8.1
Extent of exposure
The duration of iv LCM exposure, as defined in Section 3.2.4, will be summarized as a 
continuous parameter (in days). The number of LCM infusions received will be summarized 
categorically. The exposure table will be presented by age cohort, all study participants and by 
subgroup. Handling of study medication missing data is described in Section 4.2.4.
The following listings will be provided: LCM dosing history, oral LCM administration, study 
medication administration and exposure to study medication. 
8.2
Adverse events
All adverse events occurring during EP0060 (ie, after signing of the ICF) must be reported. The 
treatment-emergent adverse events (TEAEs) are defined as those events that started on or after 
the date (and time) of first infusion of study medication and within 30 days following the date of 
last study medication, or adverse events whose intensity worsened on or after the date (and time)
of first infusion of study medication and within 30 days following the last study medication 
infusion date. For OLL study participants where the adverse event started prior to EP0060 
enrollment information will come from the respective OLL study.
Only RxL and IIL study participants who do not continue LCM treatment in SP848 will have a
Telephone Contact 2 visit (Section 2.3) 30 days after the last dose follow-up.
Data handling rules for management of missing or partial start or stop dates for adverse events 
should follow those defined in the Section 4.2.3.
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 25 of 66
The following summaries will be produced:
x
Incidence of TEAEs – Overview 
x
Incidence of TEAEs  
x
Incidence of TEAEs – Study participant Numbers
x
Incidence of serious TEAEs 
x
Incidence of non-serious TEAEs
x
Incidence of serious TEAEs by relationship to LCM
x
Incidence of non-serious TEAEs by relationship to LCM
x
Incidence of other significant TEAEs (refer to Section 12.1 for a list of MedDRA 
preferred terms which define other significant TEAEs)
x
Incidence of TEAEs related to Potentially Drug Induced Liver Injury (PDILI) (refer to 
Appendix 12.4 for a list of MedDRA preferred terms which define TEAEs related to 
PDILI)
x
Incidence of TEAEs for iv Treatment Period and Post-iv Treatment Period 
x
Incidence of serious TEAEs for iv Treatment Period and Post-iv Treatment Period
x
Incidence of drug-related TEAEs
x
Incidence of TEAEs by Maximum Intensity  
x
Incidence of non-serious TEAEs occurring in at least 5% of study participants
x
Incidence of non-serious TEAEs occurring in at least 5% of study participants by 
relationship to LCM
x
Incidence of TEAEs leading to Study Discontinuation
x
Incidence of fatal TEAEs by relationship to LCM
x
Incidence of TEAEs leading to permanent discontinuation of LCM
x
Incidence of TEAEs Leading to permanent discontinuation of LCM - Study participant
Numbers 
Overview of the Incidence of AEs will include all study participants with at least one TEAE, 
serious TEAEs, non-serious TEAEs, study participant discontinuations due to TEAEs, 
permanent withdrawal of study medication due to TEAEs, drug-related TEAEs, drug-related 
serious TEAEs, severe TEAEs, all deaths (AEs leading to death), and TEAEs leading to death.
AEs will be summarized by MedDRA SOC and MedDRA PT. The tables will be presented by 
age cohort, all study participants and by subgroup. The number and percentage of study 
participants experiencing each event at least once will be summarized. All summaries will be 
sorted alphabetically by SOC and by frequency of events within PTs, starting with the most 
frequent event overall. 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 26 of 66
All AEs reported during the study will be provided in a study participant data listing. 
The following AE listings will be provided:
x
Glossary table for all TEAEs, where the terms included on the table should match those 
presented in other AE displays 
x
All AEs 
x
All serious AEs 
x
All AEs leading to study discontinuation
x
Listing of all deaths 
x
Other significant TEAEs
x
All AEs related to PDILI
x
All AEs which worsened during the study
x
All AEs which occurred under oral LCM   
Should it occur, any uncoded AEs should be designated as “UNCODED” at all MedDRA levels, 
and such AEs should be included in summary tables and study participant data listings based on 
this classification (eg, SOC and PT set to UNCODED).
8.3
Clinical laboratory evaluations
Laboratory values are collected at screening and /or baseline visit (if baseline visit is a different 
day than screening visit) and at the Final Visit. Continuous laboratory variables (hematology and 
clinical chemistry) summary statistics of actual values and change from Baseline will be 
presented by age cohort, for all study participants overall and by subgroup at each study visit.
Shifts from baseline to end of treatment based on the normal range (ie, low, normal, high, and 
missing) for each hematology and clinical chemistry lab parameter will be presented. 
The number and percentage of study participants with laboratory treatment-emergent marked 
abnormalities (TEMA) (hematology and clinical chemistry) as defined in Section 12.2 are to be 
summarized by laboratory parameter. Laboratory TEMA are those that are observed during the 
iv treatment period at scheduled or unscheduled visits and were not observed at any visit during 
the Baseline period. A study participant number table will be presented for study participants
with laboratory assessments meeting the TEMA criteria. 
The following listings will be provided: a separate study participant data listing for TEMA (all
laboratory assessments for study participants with TEMA are to be included in the listing), all 
laboratory results of clinical chemistry and hematology and serum and urine pregnancy 
laboratory tests.
Study participants who meet one or more of the criteria for potential drug-induced liver injury 
(PDILI) at any timepoint (from both scheduled and unscheduled visits) will be listed (see 
Section 12.2.3). The listing will display only visits for which at least one of the criteria in
Section 12.2.3 was fulfilled for a given study participant, and will display all results obtained at 
that visit for the specified variables. Potential Hy’s law cases will be flagged. If applicable, a 
summary of study participants who met the criteria for PDILI will be presented separately from 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 27 of 66
all relevant data collected. Results from unscheduled visits and local laboratory should be 
included, if applicable.
All potential drug-induced liver injury (PDILI) events require immediate action, testing, and 
monitoring (see Section 12.2.4). 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 included but not limited to those listed in (laboratory measurements) and 
(Appendix 12.4) (additional information).
Additional PDILI information will also be listed. If specific PDILI information collected 
separately is matching to the entries in the standard eCRF pages collected for all study 
participants, the specific PDILI information will be added to the corresponding listing for the 
standard eCRF information. For information collected on top (eg, family history of PDILI,
lifestyle) a new listing will be generated.
The number of study participants meeting the criteria for Hy’s Law will be summarized. The 
criteria of Hy’s Law are as follows:  
• (ALT or AST ≥ 3×ULN) and total bilirubin ≥ 2×ULN 
In order to meet the above criteria, a study participant must experience the elevation in total 
bilirubin and ALT or AST at the same visit. For example, a study participant who experiences a 
>=2 x ULN elevation of total 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. A study participant with ALT and AST 
values missing or a study participant with total bilirubin value missing has not fulfilled the Hy’s 
Law criteria.
8.4
Vital signs, physical findings, and other observations related to safety
8.4.1
Vital signs
Vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse rate) will be 
collected according to the protocol schedule of study assessments.
Observed values of SBP, DBP, and pulse rate will be summarized for each visit and time point.
Change from Baseline for SBP, DBP, and pulse rate will be summarized for all post-Baseline 
visits and time points. Tables will be provided by age cohort and subgroup. Actual values and 
change from Baseline for SBP, DBP and pulse rate will be plotted for a line graph by visit, time 
point, and age cohort.
Markedly abnormal (MA) vital sign values are defined as those MA post-baseline values which 
occur on or after the first EP0060 iv LCM administration through to the end of the study.
The number and percentage of study participants with MA values at each post-Baseline visit will 
be presented. Percentages will be relative to the number of study participants with a value at each
visit. Summary of MA vital signs study participant numbers will be provided. All post-baseline 
vital signs measurements (scheduled and unscheduled) will be assessed to determine MA
criteria.
The abnormal vital sign criteria are defined as follows:
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 28 of 66
Table 8‒1: Vital signs abnormality criteria
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
≥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
Temperature
>1m
>101 0F (38.3 0C)
Body Weight
1m - <17y
<3% or !97% of the normal body weight growth 
curve ranges based on gender and the age of study 
participant on date of weight assessmenta
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 29 of 66
Table 8‒1: Vital signs abnormality criteria
Parameter
Age Range
Abnormality Criteria
≥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/
A study participant data listing of all vital signs values for all study participants will be 
presented. The listing will contain a column indicating the MA criteria if a study participant had 
abnormal vital sign value. A separate study participant data listing for MA values (all vital signs 
assessments for study participants with MA values are to be included in the listing) will be 
provided.
8.4.2
Electrocardiograms (ECGs)
Standard 12-lead ECGs will be performed throughout the study according to the protocol 
schedule of assessments.
Observed the values of the ECG will be summarized for each visit. Change from Baseline in 
ECG results will be summarized for all post-Baseline visits and time points. The table will be 
presented by age cohort and subgroup. Actual values and change from Baseline will be plotted 
by visit, time point, and age cohort.
The number and percentage of study participants with normal, abnormal not clinically significant 
and abnormal clinically significant findings, as assessed by the investigator, will be summarized 
for all visits. Percentages will be relative to the number of study participants with an ECG 
assessment at each visit. Study participants are counted at most once at each visit based on the 
worst observed outcome across all abnormalities reported at that visit.
Summaries of shifts from Baseline to post-Baseline visits will also be provided based on the 
categories normal, abnormal, not clinically significant, and abnormal, clinically significant.
The number and percentage of study participants with treatment-emergent ECG abnormalities 
will be presented for each post-Baseline visit. Abnormalities reported at an unscheduled visit will 
be summarized under the scheduled visit preceding the unscheduled visit (if the abnormality was 
not present already at the preceding scheduled visit). Treatment-emergent is defined as meeting 
the criteria at any post-Baseline visit during the iv Treatment Period (including unscheduled 
visits) and not meeting the same criteria during Baseline. Abnormality criteria to be used in the 
determination of ECG abnormalities are defined as follows, where increase and decrease are 
relative to Baseline values:
Table 8‒2: ECG abnormality criteria
Parameter
Age
Abnormality Criteria
QT interval (ms)
1m-<12y
>500
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 30 of 66
Table 8‒2: ECG abnormality criteria
Parameter
Age
Abnormality Criteria
>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
3y-<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.
A listing of ECG data will be provided for all study participants with other significant TEAEs in 
the Cardiac and ECG Related Terms category defined in Appendix 12.1. A study participant data 
listing of all ECG parameter values for all study participants will also be presented. 
REDACTED 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 31 of 66
A study participant data listing will be provided that identifies study participants with a clinically 
significant finding after the first dose of iv LCM for each type of ECG abnormality. All ECG 
parameter values will be listed for study participants meeting any abnormality criteria.
8.4.3
Complete physical examination 
A complete physical examination will be performed at Screening Visit and the Final Visit 
according to the protocol schedule of study assessments.
The complete physical examination will include cardiac and respiratory function via 
auscultation, and review of all body systems. 
Clinically significant physical examination findings will be reported as AEs.
A listing of clinically significant physical examination abnormalities from the complete physical 
examination will be provided.
8.4.4
Complete neurological examination
A complete neurological examination will be performed at the Screening Visit according to the 
protocol schedule of study assessments. The complete neurological examination will include 
selected assessment of general neurological status (level of consciousness, mental status, 
speech), cranial nerves, reflexes, motor system (general motor status, muscle strength, muscle 
tone), coordination/cerebellar function, and sensation. 
Clinically significant neurological findings will be reported as AEs.
A listing of neurological examination abnormalities from the complete neurological examination 
will be provided.
8.4.5
Assessment of suicidality
Suicidality will be assessed by trained study personnel using the Columbia Suicide Severity 
Rating Scale (C-SSRS). This will be completed according to the protocol schedule of study 
assessments.
For study participants ≥6 years of age, this scale will be used for screening as well as to assess 
suicidal ideation and behavior that may occur during the study. All study participants who are ≥6 
years of age will complete the “Baseline/Screening” version of the C-SSRS at Visit 1 and will 
complete the “Since Last Visit” version at subsequent visits. If a study participant becomes 6 
years of age during the study, the “Already Enrolled” version of the C-SSRS should be used at 
the first visit at which the study participant is 6 years of age and use the “Since Last Visit” 
version at subsequent visits. 
The C-SSRS is not validated for study participants <6 years of age and will not be used for this 
population, but signs and symptoms of depression will be assessed at each visit. 
Study participant data listings of the data for the C-SSRS will be provided. No summaries of 
these results are planned.
9
PHARMACOKINETICS AND PHARMACODYNAMICS
9.1
Pharmacokinetics
All study PK outcomes will be summarized for the PK-PPS.
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 32 of 66
Blood samples for the determination of LCM and SPM 12809 concentrations will be collected 
according to the protocol schedule of study assessments (on Visit 2 and if iv LCM treatment is 
continued after Day 1 also on Visit 3, pre-dose sample is taken between -59 min to -3 min in 
relation to iv LCM infusion and +1h to 4 hours after the end of the iv LCM infusion). Additional 
blood samples for the PK analysis can be taken at the discretion of the investigator, especially in 
the event of a relevant treatment-emergent AE. Blood samples with missing sampling time will 
be excluded from the analysis.
9.1.1
Pharmacokinetics Analysis
Descriptive summaries (n, geometric mean, geometric 95% confidence interval, geometric CV, 
mean, SD, median, minimum, and maximum) for the LCM and SPM 12809 plasma 
concentrations will be presented for pre-infusion and post-infusion time points on each infusion 
day where LCM and SPM 12809 plasma are collected. Summary statistics are only calculated if 
at least 2/3 of data are above the lower limit of quantification (LOQ). Values <LOQ will be set to 
LOQ/2 for the determination of all summary statistics. Data will be presented by age cohort and 
by weight group (0 to <30kg, 30 to <50kg, >=50kg).
A listing of plasma sample collection times and plasma concentrations of LCM and SPM 12809 
will be provided.
9.2
Pharmacodynamics
This section is not applicable for this study.
10
EFFICACY ANALYSES
This section is not applicable for this study.
REDACTED 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 33 of 66
11
REFERENCES
This section is not applicable for this study.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 34 of 66
12
APPENDICES
12.1
List of Other significant AEs of VIMPAT
MedDRA Preferred Term
CARDIAC AND ECG RELATED TERMS
Atrioventricular block third degree
Atrioventricular block second degree
Bradyarrhythmia*
Bradycardia*
Cardiac pacemaker insertion
Atrial fibrillation
Atrial flutter
Sinus bradycardia*
Ventricular tachycardia
Ventricular fibrillation
Heart Rate decreased*
Sick sinus syndrome
Atrial conduction time prolongation
Atrioventricular dissociation
Conduction disorder
Cardiac fibrillation
Cardiac flutter
Sinus arrest
Torsade de pointes
Ventricular asystole
REDACTED 
ED
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 35 of 66
MedDRA Preferred Term
Ventricular flutter
Ventricular tachyarrhythmia
Implantable defibrillator insertion
SUICIDALITY RELATED TERMS
Completed suicide
Depression suicidal
Suicidal behaviour
Suicidal ideation
Suicide attempt
Intentional self-injury
Self injurious behaviour
Self-injurious ideation
Intentional overdose
Multiple drug overdose intentional
Poisoning deliberate
ADDITIONAL TERMS
Loss of consciousness
Syncope
Appetite disorder
Decreased appetite
Diet refusal
Hypophagia
Food aversion
REDACTED 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 36 of 66
MedDRA Preferred Term
Abnormal behaviour
*All cases with reported reduced heart rate will be reviewed and only cases with marked 
bradycardia (marked reduction in heart rate) with HR <45 bpm will be listed as ‘Other 
Significant AEs’.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 37 of 66
12.2
Marked abnormality criteria for laboratory data 
12.2.1
Hematology
PARAMETER
AGE 
RANG
E
UNIT 
(conventional
)
ABNORMALIT
Y CRITERIA 
(conventional)
UNIT
(standard
)
ABNORMALIT
Y CRITERIA 
(standard)
Hematocrit
<2y
%
≤27
>45
%
≤27
>45
2y -
<17y
≤29
>47
≤29
>47
≥17y
≤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 -
<17y
≤9.5
>16.0
≤95
>160
≥17y
≤85% of LLN
≥115% of ULN
≤85% of LLN
≥115% of ULN
WBC/Leukocyte
s
All
109/L
≤3.0
≥16.0
G/L
≤3.0
≥16.0
Lymphocytes 
Absolute
<2y
109/L
<1.0
>9.8
G/L
<1.0
>9.8
2y -
<6y
<0.7
>6.9
<0.7
>6.9
≥6y
<0.6
>5.0
<0.6
>5.0
Basophils
>1m
%
≥5.0
%
≥5.0
Basophils 
Absolute
>1m
109/L
≥0.4
G/L
≥0.4
REDACTED
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 38 of 66
PARAMETER
AGE 
RANG
E
UNIT 
(conventional
)
ABNORMALIT
Y CRITERIA 
(conventional)
UNIT
(standard
)
ABNORMALIT
Y CRITERIA 
(standard)
Eosinophils
>1m
%
≥10
%
≥10
Eosinophils 
Absolute
>1m
109/L
≥1.0
G/L
≥1.0
Monocytes
>1m
%
≥20.0
%
≥20.0
Monocytes 
Absolute
>1m
109/L
≥2.0
G/L
≥2.0
Neutrophils 
Absolute
>1m
109/L
<1.5
G/L
<1.5
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:  m =month, RBC=red blood cells, WBC=white blood cells, y = year. A month 
is defined as 30 days; a year is defined as 365.25 days.
12.2.2
Chemistry
PARAMETE
R
AGE 
RANG
E
UNIT 
(conventional
)
ABNORMALIT
Y CRITERIA 
(conventional)
UNIT
(standard
)
ABNORMALIT
Y CRITERIA 
(standard)
AST (SGOT)
All
U/L
≥3.0 x ULN
≥5.0 x ULN
≥10.0 x ULN
U/L
≥3.0 x ULN
≥5.0 x ULN
≥10.0 x ULN
ALT (SGPT)
All
U/L
≥3.0 x ULN
≥5.0 x ULN
≥10.0 x ULN
U/L
≥3.0 x ULN
≥5.0 x ULN
≥10.0 x ULN
REDACTED 
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3.0
OP
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 39 of 66
PARAMETE
R
AGE 
RANG
E
UNIT 
(conventional
)
ABNORMALIT
Y CRITERIA 
(conventional)
UNIT
(standard
)
ABNORMALIT
Y CRITERIA 
(standard)
Alkaline 
Phosphatase
<4y
U/L
≥690
U/L
≥690
4y -
<10y
≥834
≥834
10y -
<17y
≥1761
≥1761
≥17y
≥3.0 x ULN
≥3.0 x ULN
GGT
<6m
U/L
≥522
U/L
≥522
6m -
<1y
≥279
≥279
1y -
<13y
≥66
≥66
13y -
<17y
≥126
≥126
≥17y
≥3.0 x ULN
≥3.0 x ULN
Total Bilirubin
>1m
mg/dL
≥2.0
umol/L
≥34.208
Total Protein
2m-<1y
g/dL
<3.0
>11.9
g/L
<30
>119
1y -
<17y
<4.3
>12.0
<43
>120
≥17y
<4.3
>13.0
<43
>130
Albumin
<1y
g/dL
<1.6
>7.2
g/L
<16
>72
≥1y -
<17y
<2.4
>8.4
<24
>84
REDACTED 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 40 of 66
PARAMETE
R
AGE 
RANG
E
UNIT 
(conventional
)
ABNORMALIT
Y CRITERIA 
(conventional)
UNIT
(standard
)
ABNORMALIT
Y CRITERIA 
(standard)
≥17y
<2.6
<26
BUN
<1y
mg/dL
≥24
mmol/L
≥8.568
1y -
<17y
≥36
≥12.852
≥17y
≥40
≥14.28
Urea
<1y
mg/dL
>42
mmol/L
>7.014
≥1y
>60
>10.02
Creatinine
1y -
<10y
mg/dL
>1.2
umol/L
>106.8
10y -
<16y
>1.8
>159.12
≥16y
≥2.0
≥176.8
Creatinine 
Clearance*
All
mL/min
<50
mL/s
<0.835
Bicarbonate
>1m -
<17y
mEq/L
<15
>38
mmol/L
<15
>38
≥17y
<18
>38
<18
>38
Calcium
<1y
mg/dL
<6.9
>12.2
mmol/L
<1.725
>3.05
1y -
<17y
<7.4
>11.7
<1.85
>2.925
≥17y
≤7.6
≥11.0
≤1.9
≥2.75
Chloride
>1m
mEq/L
≤90
mmol/L
≤90
REDACTED 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 41 of 66
PARAMETE
R
AGE 
RANG
E
UNIT 
(conventional
)
ABNORMALIT
Y CRITERIA 
(conventional)
UNIT
(standard
)
ABNORMALIT
Y CRITERIA 
(standard)
≥112
≥112
Phosphorous
<1y
mg/dL
<1.8
>8.2
mmol/L
<0.5814
>2.6486
1y -
<17y
<1.8
>7.4
<0.5814
>2.3902
≥17y
≤2.0
≥6.0
≤0.646
≥1.938
Potassium
<1y
mEq/L
≤3.0
≥6.5
mmol/L
≤3.0
≥6.5
≥1y
≤3.0
≥6.0
≤3.0
≥6.0
Sodium
>1m
mEq/L
<127
>151
mmol/L
<127
>151
Glucose
>1m -
<17y
mg/dL
<50
≥180
mmol/L
<2.775
≥9.99
≥17y
<50
≥200
<2.775
≥11.1
Total 
Cholesterol
≥1y
mg/dL
>250
mmol/L
>6.475
LDL 
(calculated)
1y -
<17y
mg/dL
>140
mmol/L
>3.626
≥17y
>200
>5.18
HDL
≤2y
mg/dL
<10
mmol/L
<0.259
>2y
<20
<0.518
REDACTED
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6.
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>2.39
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 42 of 66
PARAMETE
R
AGE 
RANG
E
UNIT 
(conventional
)
ABNORMALIT
Y CRITERIA 
(conventional)
UNIT
(standard
)
ABNORMALIT
Y CRITERIA 
(standard)
Triglycerides
<1y
mg/dL
>750
mmol/L
>8.475
≥1y
>300
>3.39
Uric Acid
<1y
mg/dL
>7.7
umol/L
>457.996
1y -
<13y
>6.5
>386.62
13y -
<17y
>8.6
>511.528
≥17y
>9.5
>565.06
Thyroxine 
(T4)
<1y
ug/dL
≤4.3
≥18.4
nmol/L
≤55.3453
≥236.8264
≥1y
≤3.8
≥13.5
≤48.9098
≥173.7585
Globulin
<1y
g/dL
<1.0
>4.5
g/L
<10
>45
≥1y
<1.2
>5.3
<12
>53
Abbreviations: ALT= alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea 
nitrogen; dL = deciliter; GGT: gamma-glutamyltransferase; HDL = high density lipoprotein; LDL = 
low density lipoprotein; L = liter; 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 y): Cr Cl ml/min = [Height (cm) * 0.55] / serum creatinine; Cockroft 
equation (patients >12 y): 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.
REDACTED 
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D
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8.4
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 43 of 66
12.2.3
Required Investigations and follow up for PDILI
Abbreviations: 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 study participant also has ≥2xULN ALP, the possibility of an indication of biliary obstruction 
should be discussed with the Medical Monitor.
c 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.
REDAC
atase; 
atase; 
ACTED COPY 
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 44 of 66
12.2.4
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 heterophil 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
Hematocrit
Hemoglobin
Platelet count
RBC count
WBC count
WBC differential count
Urinalysis
Toxicology screen
Chemistry
Amylase
If total bilirubin ≥1.5xULN, obtain fractionated bilirubin to obtain % 
direct bilirubin
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transaminase elevation
ALT
AST
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GGT
Albumin
Additional
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 45 of 66
Abbreviations: ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate 
aminotransferase; CPK=creatine phosphokinase; GGT=gamma-glutamyltransferase; 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; RBC=red blood cell; 
RNA=ribonucleic acid; ULN=upper limit of normal; WBC=white blood cell.
a Measured only for study participants 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).
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations 
e
thereof. 


UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 46 of 66
12.3
Additional PDILI information
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:
x
History of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other 
“fatty liver disease”)
x
Adverse reactions to drugs
x
Allergies
x
Relevant family history or inheritable disorders (eg, Gilbert’s syndrome, alpha-1
antitrypsin deficiency)
x
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
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
PDILI=potential drug-induced liver injury
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 47 of 66
12.4
List of MedDRA Preferred Term for PDILI
MedDRA Preferred Term for PDILI
Cholestasis
Cholestatic liver injury
Cholestatic pruritus
Drug-induced liver injury
Hepatitis cholestatic
Hyperbilirubinaemia
Icterus index increased
Jaundice
Jaundice cholestatic
Jaundice hepatocellular
Mixed liver injury
Ocular icterus
Acute hepatic failure
Asterixis
Cholestatic liver injury
Coma hepatic
Cryptogenic cirrhosis
Drug-induced liver injury
Hepatic cirrhosis
Hepatic encephalopathy
Hepatic failure
Hepatic infiltration eosinophilic
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 48 of 66
Hepatic necrosis
Hepatic steatosis
Hepatitis fulminant
Hepatobiliary disease
Hepatocellular foamy cell syndrome
Hepatocellular injury
Hepatotoxicity
Liver disorder
Liver injury
Mixed liver injury
Non-alcoholic steatohepatitis
Subacute hepatic failure
Allergic hepatitis
Chronic hepatitis
Hepatitis
Hepatitis acute
Hepatitis cholestatic
Hepatitis chronic active
Hepatitis chronic persistent
Hepatitis fulminant
Hepatitis toxic
Non-alcoholic steatohepatitis
Blood bilirubin abnormal
Blood bilirubin increased
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UCB
21 June 2019
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 49 of 66
Hyperbilirubinaemia
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 50 of 66
13
AMENDMENTS TO THE STATISTICAL ANALYSIS PLAN
13.1
AMENDMENT 1
Rationale for the amendment
The primary purpose of this SAP amendment is to include subjects with the age of <4 years to
>=1 month in the second age cohort according to protocol amendment 3. In addition, non-
content related issues which were detected during the DMC-SAP review were updated.
Modifications and changes
Global changes
The following changes have been made throughout the SAP:
Text has been modified to lower the age of subject enrollment to ≥1 month of age.
x
Approximately 100 subjects will be included in EP0060.
x
Age stratification has been included within Cohort 2. Every attempt will be made to enroll 
20 subjects ≥4 to <8 years of age, 12 subjects ≥2 to <4 years of age, and 12 subjects ≥1 
month to <2 years of age.
x
Number of subjects in the DMC process in Cohort 2 has been revised.
For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to
receive iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a
duration of 30 minutes but no longer than 60 minutes whenever possible.
After completion of the first 20 subjects in Cohort 2, the DMC will review the available
safety and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC
will make recommendations as follows:
x
EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with a
target infusion duration of 15 minutes but no longer than 30 minutes only in subjects
who would directly benefit from an increased infusion rate, in the opinion of the
Investigator. Subjects who will not directly benefit from a 15 to 30 minute infusion,
in the opinion of the Investigator, cannot receive the faster infusion. These subjects
should receive an infusion of 30 minutes but no longer than 60 minutes.
x
OR approximately 30 additional subjects will be enrolled in Cohort 2 with a target
infusion duration of 30 minutes but no longer than 60 minutes.
x
OR Cohort 2 should be stopped.
x
The following changes were made to PDILI laboratory measurements:
Hematocrit, hemoglobin, platelet count, RBC count, WBC count, and WBC differential
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 51 of 66
count have replaced eosinophil count as hematology measurements.
x
The SS-iv will be the primary analysis set for the analysis of safety data and PK-PPS will
include all subjects in the SS-iv having provided at least 1 measurable postdose plasma
sample (with recorded sampling time) on at least 1 study day with documented LCM intake
times.
x
Clarifications made to the definitions of prior and concomitant medication.
x
Vital signs and ECG abnormality criteria added for age <4 years of age.
x
General updates: “e.g.”/”i.e.” to “eg,”/”ie,”, dates without non-break space, spelling 
mistakes, wording and upper/lower case corrections.
Specific changes
Change #1
Title page
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY AND
TOLERABILITY OF INTRAVENOUS LACOSAMIDE IN CHILDREN (≥4 TO <17 YEARS
OF AGE) WITH EPILEPSY
Has been changed to:
A MULTICENTER, OPEN-LABEL STUDY TO INVESTIGATE THE SAFETY AND
TOLERABILITY OF INTRAVENOUS LACOSAMIDE IN CHILDREN (≥1 MONTH TO 
<17 YEARS OF AGE) WITH EPILEPSY
Change #2
Section 1 Introduction
This SAP is based upon the following documents: (Final Protocol: 16 Dec 2014, Protocol 
Amendment 1: 21 Jul 2015, Protocol Amendment 2: 30 Nov 2016).   
Has been changed to:
This SAP is based upon the following documents: (Final Protocol: 16Dec2014, Protocol 
Amendment 1: 21Jul2015, Protocol Amendment 2: 30Nov2016, Protocol Amendment 3: 
30Apr2018).
Change #3
Section 2.1.1  Primary Objective
The primary objective of the study is to evaluate the safety and tolerability of intravenous (iv) 
Lacosamide (LCM) infusion(s) in pediatric subjects ≥4 to <17 years with epilepsy.
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 52 of 66
Has been changed to:
Section 2.1.1  Primary Objective
The primary objective of the study is to evaluate the safety and tolerability of intravenous (iv) 
Lacosamide (LCM) infusion(s) in pediatric subjects ≥1 month to <17 years with epilepsy.
Change #4
Section 2.2.3 Pharmacokinetic variables
The PK variables will include plasma concentration of LCM and its main metabolite, SPM 
12809.
Has been changed to:
Section 2.2.3 Other pharmacokinetic variables
The other PK variables will include plasma concentration of LCM and its main metabolite, SPM 
12809.
Change #5
Section 2.3 Study design and conduct
This is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of iv 
LCM infusions in pediatric subjects ≥4 to <17 years of age with epilepsy. The study will include 
approximately 75 subjects.
After completion of the first 20 subjects in Cohort 1, the Data Monitoring Committee (DMC) 
will review the safety and tolerability data from these subjects.
For Cohort 2, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but no 
longer than 60 minutes whenever possible. 
After completion of the first 10 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows:
x
EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but no longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the Investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
Investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes.
x
OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes,
x
OR Cohort 2 should be stopped,
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 53 of 66
x
AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to 
<4 years of age).  
The design will result in a total exposure of approximately 75 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations. 
Has been changed to:
Section 2.3 Study design and conduct
EP0060 is a Phase 2/3, multicenter, open-label study to evaluate the safety and tolerability of iv 
LCM infusions in pediatric subjects ≥1 month to <17 years of age with epilepsy. Based on a 
local protocol amendment only patients between ≥ 1 month to <16 years of age will be 
enrolled in Ukraine. The study will include approximately 100 subjects.
The Data Monitoring Committee (DMC) will review the safety and tolerability data from the 
first 20 subjects completed in Cohort 1.
For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to 
receive iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a duration 
of 30 minutes but not longer than 60 minutes whenever possible. 
After completion of the first 20 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows:
x
EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration of 15 minutes but not longer than 30 minutes only in subjects who would 
directly benefit from an increased infusion rate, in the opinion of the Investigator. Subjects 
who will not directly benefit from a 15 to 30 minute infusion, in the opinion of the 
Investigator, cannot receive the faster infusion. These subjects should receive an infusion of 
30 minutes but no longer than 60 minutes,
x
OR approximately 30 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but not longer than 60 minutes,
x
OR Cohort 2 should be stopped.
The design will result in a total exposure of approximately 100 pediatric subjects to assess the 
safety and tolerability of iv LCM over a range of infusion durations.
Change #6
Section 2.4
Determination of sample size
Approximately 75 subjects will be enrolled, which includes up to 2 cohorts of at least 40 subjects 
for Cohort 1and at least 20 subjects for Cohort 2. No formal sample size calculation has been 
performed. The sample size was deemed clinically appropriate for the evaluation of safety, 
tolerability, and PK of iv LCM administration in pediatric subjects with epilepsy.
The following cohorts are planned:
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 54 of 66
•
Cohort 1: at least 40 subjects from ≥8 to <17 years of age, with at least 20 subjects from ≥12 
to <17 years of age and at least 20 subjects from ≥8 to <12 years of age
•
Cohort 2: at least 20 subjects from ≥4 to <8 years of age
Has been changed to:
Approximately 100 subjects will be enrolled, which includes up to 2 cohorts of at least 40 
subjects for Cohort 1 and approximately 44 subjects for Cohort 2. No formal sample size 
calculation has been performed. The sample size was deemed clinically appropriate for the 
evaluation of safety, tolerability, and PK of iv LCM administration in pediatric subjects with 
epilepsy.
The following cohorts are planned:
x
Cohort 1: at least 40 subjects from ≥8 to <17 years of age, with at least 20 subjects from ≥12 
to <17 years of age and at least 20 subjects from ≥8 to <12 years of age
x
Cohort 2: approximately 44 subjects from ≥1 month to <8 years of age; every attempt will 
be made to enroll 20 subjects ≥4 to <8 years of age, 12 subjects ≥2 to <4 years of age, 
and 12 subjects ≥1 month to <2 years of age
Change #7
Section 3.1
General presentation of summaries and analyses
All summaries, unless otherwise stated, will be presented overall for all subjects and by the age 
cohorts (≥4 to <8 years and ≥8 to <17). Selected tables will be provided in addition by the
subject groups (OLL and RxL, and IIL) and target infusion duration (15-30 minutes, and 30-60
minutes).
Has been changed to:
All summaries, unless otherwise stated, will be presented overall for all subjects and by age 
cohorts (≥ 1 month to <8 years and ≥8 to <17). Selected tables will be provided in addition by 
subject groups (OLL and RxL, combined, and IIL) and target infusion duration (15-30 minutes, 
and 30-60 minutes).
Change #8
Section 3.2.2 Analysis periods
iv Treatment Period 
Treatment days are as follows:
(1) Clinical need administration: up to 10 doses or up to 5 days
(2) Elective administration: up to 2 consecutive doses over approximately 24 hours
End-of-Study/Final Visit (1 day) 
The iv Treatment Period is defined as the period of time from the iv LCM first dose date and 
time to the iv LCM last dose date and time, inclusive. The end date of the iv Treatment Period 
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 55 of 66
will be either the last assessment date in Visit 3 for completers, or the date of the Early 
Termination Visit (ETV) for subjects who discontinued during the iv Treatment Period. If a 
subject does not have a Visit 3/ETV, then either the date of the last scheduled or unscheduled 
visit during the iv Treatment Period or the date of last known dose of iv LCM during the iv 
Treatment Period, whichever is later, will define the end date of the iv Treatment Period.
Post-iv Treatment Period
This is defined as the period of time after the end date of the iv Treatment Period to the last 
contact with the subject.
End-of-Study/Telephone Contact 1 (1 to 3 days).
Has been changed to:
iv Treatment Period 
Treatment days are as follows:
(1) Clinical need administration: up to 10 doses or up to 5 days
(2) Elective administration: up to 2 consecutive doses over approximately 24 hours
The iv Treatment Period is defined as the period of time from the iv LCM first dose date and 
time to the iv LCM last dose date and time, inclusive. 
Post-iv Treatment Period
This is defined as the period of time after the end date and time of the iv Treatment Period to the 
last contact with the subject.
Listings will also include “Unscheduled Visit” as applicable.
Change #9
Section 3.2.3 Study visit labeling
Visits will be labeled in table summaries (according to the schedule outlined in Section 5.2 of the
protocol) as follows:
x
“Visit X (Descriptor)” for scheduled visits during the Screening/Baseline Period
x
“Visit X, Day X” for scheduled visits during the Treatment Period
x
“Final Visit, Day X”
x
“Telephone Contact, Day X”
x
“Transition Visit, Day X”
Has been changed to:
Visits will be labeled in table summaries (according to the schedule outlined in Section 5.2 of the 
protocol) as follows:
x
“Visit X (Descriptor)” for scheduled visits during the Screening/Baseline Period
x
“Visit X” for scheduled visits during the iv Treatment Period
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 56 of 66
x
“Final Visit”
x
“Telephone Contact 1”
x
“Telephone Contact 2”
x
“Transition Visit”
Change #10
Section 3.5 
Analysis sets
3.5.1 Safety Set iv
The Safety Set iv (SS-iv) will include subjects who received at least 1 dose of iv LCM. The SS-
iv will be the primary analysis set for the analysis of safety data.
3.5.2 Safety Set 
The Safety Set (SS) will include subjects who received at least 1 dose of LCM (oral or iv). 
Selected safety summaries will be presented for the SS. If the SS and the SS-iv consist of the 
same number of subjects, tables will only be presented for the SS-iv.
3.5.3 Pharmacokinetic-Per Protocol Set 
The Pharmacokinetic-Per Protocol Set (PK-PPS) will include all subjects in the SS having 
provided at least 1 measurable post-dose plasma sample (with recorded sampling time) on at 
least 1 study day with documented LCM intake times.
Has been changed to:
3.5.1   Safety Set
The Safety Set (SS) will include subjects who received at least 1 dose of EP0060 study drug
LCM (oral and/or iv). Selected safety summaries will be presented for the SS. If the SS and the 
SS-iv consist of the same number of subjects, tables will only be presented for the SS-iv.
3.5.2   Safety Set iv
The Safety Set iv (SS-iv) will include subjects in the SS who received at least 1 dose of EP0060 
study drug iv LCM. The SS-iv will be the primary analysis set for the analysis of safety data.
3.5.3
Pharmacokinetic-Per Protocol Set 
The Pharmacokinetic-Per Protocol Set (PK-PPS) will include all subjects in the SS-iv having
provided at least 1 measurable post-dose plasma sample (with recorded sampling time) on at 
least 1 study day with documented iv LCM intake times and without important protocol 
deviations impacting the interpretability of the PK analysis.
Change #11
Section 3.6
Treatment assignment and treatment groups
This is an open-label study with a single treatment arm. Subjects are summarized based on the 
age-based cohorts defined as:
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 57 of 66
•
≥8 to <17 years (Age Cohort 1)
•
≥4 to <8 years (Age Cohort 2)
Has been changed to:
This is an open-label study with a single treatment arm. Subjects are summarized based on the 
age-based cohorts defined as:
•
≥8 to <17 years (Age Cohort 1)
•
≥1 month to <8 years (Age Cohort 2)
Change #12
Section 3.9
Changes to protocol-defined analyses
In the protocol the pharmacokinetic analyses were planned to be presented by age cohort and 
infusion duration, and the IIL and OLL and RxL groups. After careful consideration, it is more 
meaningful to have the analyses presented separately by age cohort and body weight group. 
In the protocol, all safety analyses were planned to be presented by age cohort and infusion 
duration, cohorts overall, and all subjects overall and within cohort and infusion duration, by the 
Ill, OLL and RxL groups of subjects. After careful consideration, it is more meaningful to have 
all safety tables by age cohort and only specific safety tables presented by target infusion 
duration and subject group.
Has been changed to:
There are no changes to analyses specified in the protocol.
Change #13
Section 4.3
Interim analyses and data monitoring
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of the first 20 subjects in Cohort 1 and after completion of 
the first 10 subjects in Cohort 2. 
No formal stopping rule will be applied. The DMC may give a recommendation to stop the study 
after reviewing the safety data as described below. A recommendation for stopping should be 
based on the collective experience of the DMC members. After meeting to review data from each 
cohort, the DMC will provide a recommendation in writing regarding whether to continue or to 
stop the study. UCB will consider this recommendation when deciding the actions to take 
following each DMC meeting.  UCB will and ensure the study investigators are informed of the 
sponsor’s decision on how to continue as described below.
The DMC members will be defined in the DMC charter. 
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 58 of 66
LCM should be infused over a duration of 30 minutes but not longer than 60 minutes whenever 
possible.
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows:
•
EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with a target 
infusion duration as follows:
-
15 minutes but not longer than 30 minutes only in subjects who would directly benefit from 
an increased infusion rate, in the opinion of the Investigator; OR, 
-
30 minutes but not longer than 60 minutes in subjects who would not directly benefit from an 
increased infusion rate, in the opinion of the Investigator 
•
OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but not longer than 60 minutes,
•
OR the study should be stopped, 
•
AND whether Cohort 2 can be initiated.
For Cohort 2, at least 20 subjects ≥4 to <8 years of age will be enrolled to receive iv LCM. For 
the first 10 subjects in Cohort 2, iv LCM should be infused over a duration of 30 minutes but not 
longer than 60 minutes whenever possible.
After completion of the first 10 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make
recommendations as follows: 
•
EITHER approximately 15 additional subjects will be enrolled in Cohort 2 with a target 
infusion duration as follows:
-
15 minutes but not longer than 30 minutes only in subjects who would directly benefit from 
an increased infusion rate, in the opinion of the Investigator; OR,  
-
30 minutes but not longer than 60 minutes in subjects who would not directly benefit from an 
increased infusion rate, in the opinion of the Investigator
•
OR approximately 15 additional subjects will be enrolled in Cohort 2 with a target infusion 
duration of 30 minutes but no longer than 60 minutes, 
•
OR Cohort 2 should be stopped,. 
•
AND whether to initiate a new iv LCM study in younger pediatric subjects (≥1 month to <4 
years of age).
Has been changed to:
No formal interim analysis is planned for this study; however, data will be presented to and 
reviewed by a DMC after completion of the first 20 subjects in Cohort 1 and after completion of 
the first 20 subjects in Cohort 2. 
No formal stopping rule will be applied. The DMC may give a recommendation to stop the study 
after reviewing the safety data as described below. A recommendation for stopping should be 
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 59 of 66
based on the collective experience of the DMC members. After meeting to review data from each 
cohort, the DMC will provide a recommendation in writing regarding whether to continue or to 
stop the study. UCB will consider this recommendation and ensure the study investigators are 
informed of the sponsor’s decision on how to continue as described below.
The DMC members will be defined in the DMC charter. 
EP0060 will begin with Cohort 1, where at least 40 subjects ≥8 to <17 years of age will be 
enrolled to receive iv LCM. Within Cohort 1, at least 20 subjects will be ≥12 to <17 years of age 
and at least 20 subjects will be ≥8 to <12 years of age. For the first 20 subjects in Cohort 1, iv 
LCM should be infused over a duration of 30 minutes but not longer than 60 minutes whenever 
possible.
After completion of the first 20 subjects in Cohort 1, the DMC will review the safety and 
tolerability data from these subjects. Based on this review, the DMC will make recommendations 
as follows:
x
EITHER approximately 30 additional subjects will be enrolled in Cohort 1 with target 
infusion durations as follows:
-
15 minutes but not longer than 30 minutes only in subjects who would directly benefit 
from an increased infusion rate, in the opinion of the Investigator; OR, 
-
30 minutes but not longer than 60 minutes in subjects who would not directly benefit 
from an increased infusion rate, in the opinion of the Investigator 
x
OR approximately 30 additional subjects will be enrolled in Cohort 1 with a target infusion 
duration of 30 minutes but not longer than 60 minutes,
x
OR study should be stopped, 
x
AND whether Cohort 2 can be initiated.
For Cohort 2, approximately 44 subjects ≥1 month to <8 years of age will be enrolled to 
receive iv LCM. For the first 20 subjects in Cohort 2, iv LCM should be infused over a duration 
of 30 minutes but no longer than 60 minutes whenever possible.
After completion of the first 20 subjects in Cohort 2, the DMC will review the available safety 
and tolerability data from Cohort 1 and Cohort 2. Based on this review, the DMC will make 
recommendations as follows: 
x
EITHER approximately 30 additional subjects will be enrolled in Cohort 2 with target 
infusion durations as follows:
-
15 minutes but not longer than 30 minutes only in subjects who would directly benefit 
from an increased infusion rate, in the opinion of the Investigator; OR,  
-
30 minutes but not longer than 60 minutes in subjects who would not directly benefit 
from an increased infusion rate, in the opinion of the Investigator
x
OR approximately 30 additional subjects will be enrolled in Cohort 2 with target infusion 
duration of 30 minutes but not longer than 60 minutes, 
x
OR Cohort 2 should be stopped. 
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 60 of 66
Change #14
Section 5.1 Subject disposition
A summary of disposition of analysis sets will be provided for all subjects screened and the SS-
iv:
The following listings will be provided: study eligibility criteria text, subjects who did not meet 
study eligibility criteria, subject disposition, study discontinuation, subject analysis sets, subjects 
excluded from at least one analysis set, and visit dates.
Has been changed to:
A summary of disposition of analysis sets will be provided for all subjects screened:
The following listings will be provided: subjects who did not meet study eligibility criteria, 
subject disposition, study discontinuation, subject analysis sets, subjects excluded from at least 
one analysis set, visit dates, and subject number.
Change #15
Section 6.1 Demographics and other Baseline characteristics
Demographic variables will be presented for the SS-iv and the SS. The variables to be considered 
are:
•
Age at entry into EP0060 (as defined in Section 3.1.6) – continuous and categorized as 
•
For EudraCT age categories are >=4 to <12 years and >=12 to <=17 years and the age cohort 
categories are >=4 to <8 years, >=8 to <12 years and >=12 to <17 years.
Has been changed to:
Section 6.1 Demographics and other Baseline characteristics
Demographic variables will be presented for the SS-iv and the SS. The variables to be considered 
are:
•
Age at entry into EP0060 
•
Categorized age:
o
EudraCT age categories: >=1 month to < 2 years, >=2 to <12 years and >=12 to
<17 years 
o
Age cohort categories: >=1 month to < 2 years, >=2 to <4 years, >=4 to <8 years, >=8 
to <12 years and >=12 to <17 year
Change #16
Section 6.2 Medical history
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 61 of 66
Medical history for RxL and IIL will be obtained from the Screening Visit Medical History 
eCRF module in EP0060. Medical History for OLL subjects is the sum of their medical history 
from their respective previous study and if applicable data from the subject's Medical History 
update form in EP0060.
Has been changed to:
Medical history for RxL and IIL will be obtained from the Screening Visit Medical History 
eCRF module in EP0060. Medical History for OLL subjects will come from their medical 
history from their respective previous.
Change #17
Section 6.4.2 History of seizure characteristics
History of epileptic seizures, history of status epilepticus, age at diagnosis (as defined in 
Section 3.2.5), time since first epileptic seizure (as defined in Section 3.2.6 ), and time since last 
status epilepticus (as defined in Section 3.2.6) will be summarized and listed where available. 
For direct enrollers, this information will be collected in the History of Epileptic Seizures eCRF 
for EP0060. For OLL subjects this information will come from their previous study.
Has been changed to:
History of withdrawal seizures, history of status epilepticus, age at first diagnosis (as defined in 
Section 3.2.5), time since first epileptic seizure (as defined in Section 3.2.6), and time since last 
status epilepticus (as defined in Section 3.2.6) will be summarized and listed where available. 
For direct enrollers, this information will be collected in the History of Epileptic Seizures eCRF 
for EP0060. For OLL subjects this information will come from their previous study.
Change #18
Section 6.5 
Prior and concomitant medications
Added: 
Prior medications include any medications that started prior to the date of first dose of LCM 
study drug.  Concomitant medications are medications taken at least one day in common with 
study drug LCM in EP0060. Medications may be both prior and concomitant.
Change #19
Section 6.5.1     Concomitant Non-AEDs
Non-AEDs taken at any time during the Treatment Period will be considered as concomitant 
medications. Medications will be summarized by ATC Code level 1 and 2 for the SS-iv. Subjects 
reporting multiple medications within an ATC class are counted once per medication and class.
Section 6.5.2
Concomitant AEDs
AEDs are reported on the Concomitant Medications (AEDs only) eCRF as concomitant 
medications. Concomitant AEDs will be summarized by Level 4 ATC code and generic 
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 62 of 66
medication name. If a medication identified as an AED does not code to a level 4 ATC code, the 
highest level of coding will be displayed along with the generic medication name. Summaries of 
AEDs will be presented separately from other concomitant medications for the SS-iv population.
Has been changed to:
Section 6.5.1     Concomitant Non-AEDs
Non-AEDs taken at least one day in common with LCM study drug in EP0060 will be 
considered as concomitant medications. Medications will be summarized by ATC Code level 1 
and 2 for the SS-iv. Subjects reporting multiple medications within an ATC class are counted 
once per medication and class. 
Section 6.5.2     Concomitant AEDs
Concomitant AEDs are defined as AEDs taken concomitantly for at least one day in 
common with LCM study drug in EP0060. AEDs are reported on the Concomitant 
Medications (AEDs only) eCRF page. Concomitant AEDs will be summarized by Level 4 ATC 
code and generic medication name. If a medication identified as an AED does not code to a level 
4 ATC code, the highest level of coding will be displayed along with the generic medication 
name. Summaries of AEDs will be presented separately from other concomitant medications for 
the SS-iv population.
Change #20
Section 8.2 Adverse events
AE Summaries
x
Incidence of AEs – Overview 
Has been changed to:
x
Incidence of TEAEs – Overview 
Added:
x
Incidence of TEAEs related to Potentially Drug Induced Liver Injury (PDILI) (refer to 
Appendix 12.4 for a list of MedDRA preferred terms which define TEAEs related to 
PDILI)
AE Listings
Added:
x
All AEs related to PDILI
Change #21
Section 8.3 Clinical laboratory evaluations
Added:
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 63 of 66
The number of subjects meeting the criteria for Hy’s Law should also be summarized. The 
criteria of Hy’s Law are as follows:  
• (ALT or AST ≥ 3×ULN) and total bilirubin ≥ 2×ULN 
In order to meet the above criteria, a subject must experience the elevation in total bilirubin and 
ALT or AST at the same visit. For example, a subject who experiences a >=2 x ULN elevation 
of total 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. A subject with ALT and AST values missing or a subject with 
total bilirubin value missing has not fulfilled the Hy’s Law criteria.
Change #22
Section 8.4.5   Assessment of suicidality
Suicidality will be assessed by trained study personnel using the C-SSRS (Columbia University 
Medical Center, 2008). This will be completed according to the protocol schedule of study 
assessments.
For subjects ≥6 years of age, this scale will be used for screening as well as to assess suicidal 
ideation and behavior that may occur during the study. All subjects who are ≥6 years of age will 
complete the “Baseline/Screening” version of the C-SSRS at Visit 1 and will complete the 
“Since Last Visit” version at subsequent visits. If a subject becomes 6 years of age during the 
study, the “Already Enrolled” version of the C-SSRS should be used at the first visit at which the 
subject is 6 years of age and use the “Since Last Visit” version at subsequent visits. 
The C SSRS is not validated and will not be used for subjects <6 years of age. For those subjects, 
signs and symptoms of depression will be assessed at each visit. 
Subject data listings of the data for the C-SSRS will be provided. No summaries of these results 
are planned.
Has been changed to:
Suicidality will be assessed by trained study personnel using the Columbia Suicide Severity 
Rating Scale (C-SSRS). This will be completed according to the protocol schedule of study 
assessments.
For subjects ≥6 years of age, this scale will be used for screening as well as to assess suicidal 
ideation and behavior that may occur during the study. All subjects who are ≥6 years of age will 
complete the “Baseline/Screening” version of the C-SSRS at Visit 1 and will complete the 
“Since Last Visit” version at subsequent visits. If a subject becomes 6 years of age during the 
study, the “Already Enrolled” version of the C-SSRS should be used at the first visit at which the 
subject is 6 years of age and use the “Since Last Visit” version at subsequent visits. 
The C-SSRS is not validated for subjects <6 years of age and will not be used for this 
population, but signs and symptoms of depression will be assessed at each visit. 
Subject data listings of the data for the C-SSRS will be provided. No summaries of these results 
are planned.
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 64 of 66
Change #23
Section 9.1 Pharmacokinetics
Blood samples for the determination of LCM and SPM 12809 concentrations will be collected 
according to the protocol schedule of study assessments (on Visit 2 and 3, pre-dose between -
59min to -3min in relation to iv LCM infusion and +1h to 4 hours after the end of the iv LCM 
infusion). Additional blood samples for PK analysis can be taken at the discretion of the 
investigator, especially in the event of a relevant treatment-emergent AE.
Has been changed to:
Blood samples for the determination of LCM and SPM 12809 concentrations will be collected 
according to the protocol schedule of study assessments (on Visit 2 and if iv LCM treatment is 
continued after Day 1 also on Visit 3, pre-dose sample is taken between -59 min to -3 min in 
relation to iv LCM infusion and +1h to 4 hours after the end of the iv LCM infusion). Additional 
blood samples for the PK analysis can be taken at the discretion of the investigator, especially in 
the event of a relevant treatment-emergent AE. Blood samples with missing sampling time 
will be excluded from the analysis.
Change #24
Table 8‒1: Vital signs abnormality criteria
Criteria for age <4 years of age were added.
Table 8‒2: ECG abnormality criteria
Criteria for age <4 years of age were added.
Appendices 12.1 List of Other significant AEs of VIMPAT
List of Other significant AEs of VIMPAT has been updated
Appendices 12.2.4 PDILI laboratory measurements
List of hematology PDILI laboratory measurements has been updated.
List of chemistry PDILI laboratory measurements has been updated.
Appendices 12.4 List of MedDRA Preferred Term for PDILI
List of MedDRA Preferred Term for PDILI was added.
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 65 of 66
13.2
AMENDMENT 2
Change #1
Section 3.2.5 Age and Age at first diagnosis
Age will be given in years and will be derived applying the rules for missing data imputation 
(see Section 4.2.1 and the SDTM derivation definition). The age at first diagnosis will be given 
in years and will be derived applying all rules for missing data imputation (see Section 4.2.1) 
with the following formula: 
(Date of first diagnosis of epilepsy – Date of birth) / 365.25
Has been changed to:
Age will be given in years and will be derived applying the rules for missing data imputation 
(see Section 4.2.1 and the SDTM derivation definition). The age at first diagnosis will be given 
in years and will be derived applying all rules for missing data imputation (see Section 4.2.1) 
with the following formulas:
Missing or partial epilepsy diagnosis date will be derived applying all rules for missing data 
imputation (see Section 4.2.1) and age at first diagnosis will use the following formulas,
where applicable.
The following formula will be applied where birthdate is a complete date: 
(Date of first diagnosis of epilepsy – Date of birth) / 365.25
The following formula will be applied where birthdate is a partial date:
(Enrollment age in years) – [(Informed consent date – Epilepsy diagnosis date) / 365.25], if
the value is negative then age at diagnosis will be set to zero.
Change #2
Change the word “subject” to “study participant” throughout the document. 
Change the word “subject” to “patient” in part of section 2.3, study design and conduct.
REDACTED
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UCB
02 July 2018
Statistical Analysis Plan
Lacosamide
EP0060
Confidential
Page 66 of 66
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures below indicate that the final version of 
the SAP or amended SAP is released for execution.
COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.