Clinical trial NCT01921205
Conditions: Epilepsy
Keywords: Lacosamide Vimpat UCB Epilepsy Partial Onset Seizures Pediatric
Sponsor: UCB Pharma
Start date: 2013-08-29; Completion date: 2017-01-24
Enrollment: 404 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Study to evaluate the efficacy of Lacosamide (LCM) administered in addition to 1 to ≤3 other Anti-Epileptic Drugs in subjects with epilepsy ≥4 years to \<17 years of age who currently have uncontrolled partial onset seizures.

Detailed description:
The primary objective of this study is to evaluate the efficacy of LCM administered concomitantly with 1 to ≤3 Anti-Epileptic Drugs (AEDs) in subjects with epilepsy ≥4 years to \<17 years of age who currently have uncontrolled partial onset seizures.

The secondary objective is to evaluate the safety and tolerability of LCM in subjects ≥4 years to \<17 years of age.

An additional objective is to evaluate the pharmacokinetics (PK) of LCM in subjects ≥4 years to \<17 years of age.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Lacosamide intervention 2: Placebo
Intervention descriptions: intervention 1: Subjects \<30 kg (LCM oral solution): 4 mg/kg - 6 mg/kg BID ( 8mg/kg/day - 12 mg/kg/day)

Subjects ≥30 kg to \<50 kg (LCM oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day)

Subjects ≥50 kg (LCM tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day) intervention 2: Subjects \<30 kg (placebo oral solution): 4 mg/kg - 6 mg/kg BID (8 mg/kg/day - 12 mg/kg/day)

Subjects ≥30 kg to \<50 kg (placebo oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day)

Subjects ≥50 kg (placebo tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day)

Protocol documents:
Prot_001.pdf: 
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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 1of 97
PROTOCOL SP0969AMENDMENT 1
A MULTICENTER, DOUBLE-BLIND, RANDOMIZED, 
PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO 
INVESTIGATE THE EFFICACY AND SAFETY OF 
LACOSAMIDE AS ADJUNCTIVE THERAPY IN SUBJECTS 
WITH EPILEPSY ≥4YEARS TO <17YEARS OF AGE WITH 
PARTIAL-ONSET SEIZURES
PHASE 3
EudraCT Number: 2012-004996-38
IND Numbers: 73809 and 57939
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Protocol/Amendment number
Date
Type of 
amendment
Protocol
22May 2013 
Not applicable
Protocol Amendment 1
05 Mar 2015 
Substantial
Confidential Material
Confidential
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on, reproduced, published, or otherwise used without the express permission of 
UCB.
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STUDY CONTACT INFORMATION
Sponsor
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Principal/Coordinating Investigator
Will be listed separately.
Sponsor Study Physician
Name:
, MD
Address:
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8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
Fax:
Clinical Project Manager 
Name:
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Address:
UCB BIOSCIENCES, GmbH.
Alfred-Nobel-Str. 10
40789 Monheim
GERMANY
Phone:
Fax:
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SP0969
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Clinical Trial Biostatistician 
Name:
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Address:
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SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World:+32 2 386 2421
USA: +1 800 880 6949
Canada:+1 877 582 8842
Email
Global: DSICT@ucb.com
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Lacosamide
SP0969
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TABLE OF CONTENTS
LIST OF ABBREVIATIONS.................................................................................................. 10
1
SUMMARY..................................................................................................................... 12
2
INTRODUCTION ................................ ................................ ........................................... 12
3 STUDY OBJECTIVES.................................................................................................... 15
4
STUDY VARIABLES..................................................................................................... 15
4.1
Efficacy variables................................................................................................... 15
4.1.1
Primary efficacy variable............................................................................. 15
4.1.2
Secondary efficacy variables....................................................................... 15
4.1.3
Other efficacy variables 
................................ 
............................................... 16
4.2
Safety variables...................................................................................................... 16
4.2.1
Primary safety variables............................................................................... 16
4.2.2 
Other safety variables.................................................................................. 16
4.3 
Pharmacokinetic and pharmacodynamic variables................................................ 16
5
STUDY DESIGN............................................................................................................. 17
5.1
Study description................................................................................................... 17
5.1.1
Study duration per subject ................................ ........................................... 18
5.1.2 
Planned number of subjects and sites .......................................................... 19
5.1.3 
Anticipated regions and countries................................................................ 19
5.2 
Schedule of study assessments............................................................................... 19
5.3
Schematic diagram................................................................................................. 27
5.4 
Rationale for study design and selection of dose................................................... 32
6
SELECTION AND WITHDRAWAL OF SUBJECTS................................................... 33
6.1
Inclusion criteria ................................ ................................ .................................... 33
6.2
Exclusion criteria 
................................ 
................................ 
................................... 34
6.3 
Withdrawal criteria ................................ ................................ ................................ 35
7 STUDY TREATMENTS................................................................................................. 37
7.1 
Description of investigational medicinal products ................................................ 37
7.2 
Treatments to be administered 
................................ 
............................................... 37
7.2.1 
Titration Period 
................................ 
............................................................ 37
7.2.2 
Maintenance Period..................................................................................... 40
7.2.3 
Transition Period (for subjects who plan to enter EP0034)......................... 40
7.2.4 
Taper Period (for subjects not entering EP0034)......................................... 41
7.3
Packaging............................................................................................................... 42
7.4 
Labeling ................................ ................................ ................................................. 42
7.5 
Handling and storage requirements ................................ ....................................... 42
7.6
Drug accountability................................................................................................ 43
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Planned number of subjects and sites
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Planned number of subjects and sites
Anticipated regions and countries
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Anticipated regions and countries
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y design and selection of dose
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y design and selection of dose
ECTION AND WITHDR
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ECTION AND WITHDRAWAL
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AWAL
................................
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................................
clusion criteria
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clusion criteria................................
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Withdrawal criteria
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Withdrawal criteria
STUDY TREATMENTS
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STUDY TREATMENTS
Description of investigational medicinal products
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Description of investigational medicinal products
Treatments to be administered
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Treatments to be administered
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7.2.1 
Titration Period 
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7.2.1 
Titration Period 
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7.2.2
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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
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Page 6of 97
7.7 
Procedures for monitoring subject compliance...................................................... 43
7.8 
Concomitant medications/treatments..................................................................... 43
7.8.1 
Permitted and prohibited concomitant treatments (medications an 
d 
therapies)...................................................................................................... 43
7.8.2 
Rescue medication 
................................ 
....................................................... 44
7.9 
Blinding.................................................................................................................. 44
7.9.1 
Procedures for maintaining and breaking the treatment blind..................... 45
7.9.1.1 
Maintenance of study treatment blind................................................ 45
7.9.1.2 
Breaking the treatment blind in an emergency situation.................... 45
7.10 Randomization and numbering of subjects............................................................ 45
8 STUDY PROCEDURES BY VISIT ................................ ............................................... 45
8.1 
Baseline Period: Week -8 to Week 0 
................................ 
..................................... 46
8.1.1 
Baseline Period: Visit1 (Week-8) (Screening) .......................................... 46
8.1.2 
Baseline Period: Telephone Contact 1 (Week -4)....................................... 47
8.1.3 
Baseline Period: Visit2 (Week0) (Randomization) ................................... 47
8.2 
Titration Period: Week 1 to Week 6 
................................ 
...................................... 48
8.2.1 
Titration Period: Telephone Contact2 (Week1), Telephone Contact 3 
(Week3), and Telephone Contact4 (Week5) ............................................ 49
8.2.2 
Titration Period: Visit3 (Week2), Visit4 (Week4), and Visit 5 
(Week6) ................................ ................................ ...................................... 49
8.3 
Maintenance Period: Week 7 to Week 16.............................................................. 50
8.3.1 
Maintenance Period: Visit6 (Week8) and Visit7 (Week12) 
.................... 50
8.3.2 
Maintenance Period: Telephone Contact5 (Week10) and Telephone 
Contact6 (Week14) 
................................ 
.................................................... 51
8.3.3 
End of Maintenance Period: Visit8 (Week16)........................................... 51
8.4 
Transition Period.................................................................................................... 53
8.4.1 
Transition Period: Transition Visit1 (Week17), Transition Visit 2 
(Week18), and Transition Visit 3 (Week 19) ............................................. 53
8.4.2 
Transition Period: Transition Visit4 (Week20) ......................................... 54
8.5
Taper Period........................................................................................................... 54
8.5.1 
Taper Period: Telephone Contact7 (Week17) ........................................... 55
8.5.2 
Taper Period: Taper Visit (Week 18, Week19, or Week20) ..................... 55
8.6
Safety Follow-Up Period....................................................................................... 56
8.6.1
Safety Follow-Up Visit................................................................................ 56
8.6.2
Safety Follow-Up Telephone Contact ......................................................... 57
8.7 
Unscheduled Visit.................................................................................................. 57
8.8
Early Termination Visit......................................................................................... 57
9 ASSESSMENT OF EFFICACY...................................................................................... 59
9.1
Specification of efficacy parameters...................................................................... 59
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4)
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0) (Randomization)
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0) (Randomization)
Period: Week 1 to Week 6 
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Period: Week 1 to Week 6 
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2 (Week
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4 (Week
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4 (Week
3 (Week
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3 (Week2), Visit
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2), Visit
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7 to Week 16................................
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7 to Week 16................................
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Maintenance Period: Visit
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Maintenance Period: Visit6 (Week
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6 (Week14) 
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14) 
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End of Maintenance Period: Visit
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End of Maintenance Period: Visit
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Period
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Transition Period: Transition Visit
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Transition Period: Transition Visit
(Week
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Transition Period: Transition Visit
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Taper Period: Taper Visit (Week
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Clinical Study Protocol
Lacosamide
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9.2 
Methods for assessing efficacy parameters............................................................ 60
9.2.1
Primary and secondary efficacy parameters 
................................................ 60
9.2.2
Other efficacy parameters 
................................ 
............................................ 60
9.2.2.1 
Clinical and Caregiver’s Global Impression of Change.................... 60
9.2.2.2 
Healthcare resource use ................................ ..................................... 60
9.2.2.3
PedsQL............................................................................................... 60
10 ASSESSMENT OF PHARMACOKINETIC/ PHARMACODYNAMIC 
VARIABLE(S) ................................ ................................ ................................................ 61
11 ASSESSMENT OF SAFETY.......................................................................................... 61
11.1 Adverse events....................................................................................................... 61
11.1.1 Definition of adverse event.......................................................................... 61
11.1.2 Procedures for reporting and recording adverse events............................... 61
11.1.3 Description of adverse events 
................................ 
...................................... 62
11.1.4 Follow up of adverse events ................................ ........................................ 62
11.1.5 Rule for repetition of an adverse event........................................................ 62
11.1.6
Pregnancy..................................................................................................... 62
11.1.7 Overdose of investigational medicinal product ........................................... 63
11.1.8
Safety signal detection................................................................................. 63
11.2 Serious adverse events 
................................ 
........................................................... 63
11.2.1 Definition of serious adverse event ............................................................. 63
11.2.2 Procedures for reporting serious adverse events.......................................... 64
11.2.3 Follow up of serious adverse events 
............................................................ 65
11.3 Adverse events of special interest.......................................................................... 65
11.4 Immediate reporting of adverse events 
................................ 
.................................. 66
11.5 Anticipated serious adverse events 
................................ 
........................................ 66
11.6 Laboratory measurements...................................................................................... 67
11.7 Liver function tests ................................ ................................ ................................ 68
11.8 Pregnancy testing................................................................................................... 69
11.9 Other safety measurements.................................................................................... 69
11.9.1
Physical examination 
................................ 
................................................... 69
11.9.1.1
Complete physical examination 
......................................................... 69
11.9.1.2
Brief physical examination................................................................ 69
11.9.2 Neurological examination............................................................................ 69
11.9.2.1 
Complete neurological examination .................................................. 69
11.9.2.2 
Brief neurological examination.......................................................... 70
11.9.3 Vital signs, body weight, and height............................................................ 70
11.9.4 12-lead ECG ................................ ................................ ................................ 70
11.9.5
Overall ECG interpretation.......................................................................... 70
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11.1.2 Procedures for reporting and recording adverse events............................... 61
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11.1.2 Procedures for reporting and recording adverse events............................... 61
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................................
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Overdose of investigational medicinal product
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Overdose of investigational medicinal product
................................
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................................
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Definition of serious adverse event
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Definition of serious adverse event
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11.2.2 Procedures for reporting serious adverse events................................
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11.2.2 Procedures for reporting serious adverse events................................
Follow up of serious adverse events
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11.3 Adverse events of special interest................................
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11.3 Adverse events of special interest................................
Immediate reporting of adverse events
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 measurements
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 measurements
Liver function tests
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Pregnancy
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11.9.1
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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
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Page 8of 97
11.9.6
Tanner Stage................................................................................................ 70
11.9.7 Achenbach CBCL 
................................ 
........................................................ 70
11.9.8 Assessment of suicidality................................ ............................................. 71
11.9.9
BRIEF-P and BRIEF ................................ ................................................... 72
12 STUDY MANAGEMENT AND ADMINISTRATION 
................................................. 72
12.1 Adherence to protocol............................................................................................ 72
12.2 Monitoring ................................ ................................ ............................................. 72
12.2.1 Definition of source data.............................................................................. 73
12.2.2 Source data verification ................................ ............................................... 73
12.3 Data handling 
................................ 
................................ 
......................................... 73
12.3.1 Case Report form completion 
................................ 
...................................... 73
12.3.2
Database entry and reconciliation................................................................ 74
12.3.3 Subject Screening and Enrollment log/Subject Identification C ode list...... 74
12.4 Termination of the study........................................................................................ 74
12.5 Archiving and data retention.................................................................................. 74
12.6 Audit and inspection 
................................ 
.............................................................. 75
12.7 Good Clinical Practice 
................................ 
........................................................... 75
13 STATISTICS................................................................................................................... 75
13.1 Definition of analysis sets...................................................................................... 75
13.2 General statistical considerations........................................................................... 76
13.3 Planned efficacy analyses...................................................................................... 76
13.3.1
Analysis of the primary efficacy variable.................................................... 76
13.3.2
Analysis of secondary efficacy variables..................................................... 76
13.3.3
Other efficacy analyses................................................................................ 77
13.4 Planned safety and other analyses.......................................................................... 77
13.4.1
Safety analyses............................................................................................. 77
13.4.2 Pharmacokinetic analyses............................................................................ 78
13.4.2.1 
Descriptive statistics of LCM and AED plasma concentrations........ 78
13.4.3 Population pharmacokinetics....................................................................... 78
13.4.3.1
Exposure-response............................................................................. 78
13.5 Handling of protocol deviations............................................................................. 78
13.6 Handling of dropouts or missing data.................................................................... 79
13.7 Planned interim analysis and data monitoring 
....................................................... 79
13.8 Determination of sample size................................................................................. 79
14 ETHICS AND REGULATORY REQUIREMENTS...................................................... 80
14.1 Informed consent ................................ ................................ ................................... 80
14.2 Subject identification cards.................................................................................... 81
14.3 Institutional Review Boards and Independent Ethics Committees........................ 81
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General statistical considerations
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es
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es................................
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................................
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............................ 72
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............................ 72
............. 72
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............. 72
.............. 73
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.............. 73
............... 73
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............... 73
................................
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................................
................................
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................................
................................ 74
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................................ 74
12.3.3 Subject Screening and Enrollment log/Subject Identification C ode list...... 74
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12.3.3 Subject Screening and Enrollment log/Subject Identification C ode list...... 74
................................
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................................
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General statistical considerations
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General statistical considerations................................
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................................
................................
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sis of the primary
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 efficacy
sis of the primary efficacy
sis of the primary
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sis of the primary efficacy
sis of the primary
sis of secondary
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sis of secondary
Other efficacy
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Other efficacy
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Other efficacy anal
Other efficacy
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y and other anal
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y and other anal
Safety
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Safety anal
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Safety anal
Safety
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Safety anal
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Pharmacokinetic anal
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13.4.2.1
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13.4.3
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13.4.3
Population pharmacokinetics
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13.4.3.1
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13
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13.5 Handling of protocol deviations................................
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.5 Handling of protocol deviations................................
13.6 Handling of dropouts or missing data................................
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13.6 Handling of dropouts or missing data................................
13.7
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13.7


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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 9of 97
14.4 Subject privacy....................................................................................................... 82
14.5 Protocol amendments............................................................................................. 82
15 FINANCE, INSURANCE, AND PUBLICATION......................................................... 82
16 REFERENCES ................................ ................................ ................................................ 82
17 APPENDICES................................................................................................................. 84
17.1 Protocol amendment 1 ................................ ........................................................... 84
18 DECLARATION AND SIGNATURE OF INVESTIGATOR ....................................... 96
19 SPONSOR DECLARATION 
................................ 
.......................................................... 97
LIST OF TABLES
Table 5-1 Schedule of study assessments (Baseline Period, Titration Period, 
Maintenance Period, Early Termination Visit, and Unscheduled Visits)............. 20
Table 5-2 Schedule of study assessments (Transition Period).............................................. 24
Table 5-3 Schedule of study assessments (Taper Period and Safety Follow-Up 
Period)................................................................................................................... 25
Table 7‒1: Recommended dosing schedule for LCM (or matching placebo) during 
the Titration Period 
................................ 
............................................................... 38
Table 7‒2: Dosing of LCM (or matching placebo) with flexibility based on 
tolerability during the Titration Period 
................................ 
................................. 39
Table 7‒3: Required LCM (or matching placebo) dose for at least the final 3days of 
Week 6 
................................ 
................................ 
.................................................. 40
Table 7‒4: Transition Period LCM dosing schedule for subjects randomized to 
placebo.................................................................................................................. 41
Table 7‒5: Taper Period dosing of LCM (or matching placebo)............................................ 42
Table 11-1Anticipated SAEs for the pediatric epilepsy population....................................... 67
Table 11-2Laboratory measurements..................................................................................... 68
LIST OF FIGURES
Figure5‒1: SP0969 overall schematic diagram....................................................................... 28
Figure5‒2: SP0969 schematic diagram (Transition Period) 
................................................... 30
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................................
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................................
Recommended dosing schedule for LCM (or matching placebo) durin
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Recommended dosing schedule for LCM (or matching placebo) durin
................................
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................................
Dosing of LCM (or matching placebo) with flexibility based on 
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Dosing of LCM (or matching placebo) with flexibility based on 
 during the Titration Period
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 during the Titration Period
CM (or matching placebo) dose for at least the final 3
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CM (or matching placebo) dose for at least the final 3
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........................... 84
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........................... 84
....... 96
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....... 96
.......................... 97
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.......................... 97
(Baseline Period, Titration Period, 
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(Baseline Period, Titration Period, 
Maintenance Period, Early Termination Visit, and Unscheduled Vi
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Maintenance Period, Early Termination Visit, and Unscheduled Vi
 assessments (Transition Period)................................
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 assessments (Transition Period)................................
y assessments (Taper Period and Safety Follow
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y assessments (Taper Period and Safety Follow
................................
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................................
Recommended dosing schedule for LCM (or matching placebo) durin
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Recommended dosing schedule for LCM (or matching placebo) durin
................................
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................................
Dosing of LCM (or matching placebo) with flexibility based on 
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Dosing of LCM (or matching placebo) with flexibility based on 
 during the Titration Period
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 during the Titration Period
CM (or matching placebo) dose for at least the final 3
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CM (or matching placebo) dose for at least the final 3
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................................
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................................................................
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................................
Transition Period LCM dosing schedule for subjects randomized to 
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Transition Period LCM dosing schedule for subjects randomized to 
................................
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................................
Taper Period dosing of LCM (or matching placebo)
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Taper Period dosing of LCM (or matching placebo)
Anticipated SAEs for the pediatric epileps
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Anticipated SAEs for the pediatric epileps
Laboratory measur
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Laboratory measur
Figure
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Figure
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5
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5‒1:
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‒1:
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Figure5
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5


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 10of 97
LIST OF ABBREVIATIONS
AE
adverse event
AED
antiepileptic drug
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
AV
atrioventricular
bid
twice daily
BP
blood pressure
BRIEF®
Behavior Rating Inventory of Executive Function®
BRIEF®-P
Behavior Rating Inventory of Executive Function®-Preschool Version
CBCL
Child Behavior Checklist
CDMS
clinical data management system
CPM
Clinical Project Manager
CRF
Case Report form
CRO
contract research organization
C-SSRS
Columbia-Suicide Severity Rating Scale
DAP
Data Analysis Plan
ECG
electrocardiogram
eCRF
electronic Case Report form
EEG
electroencephalogram
EI-AED
enzyme-inducing antiepileptic drug
FAS
Full Analysis Set
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
HDPE
high density polyethylene
HRQoL
health-related quality of life
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IMP
investigational medicinal product
IRB
Institutional Review Board
iv
intravenous
REDACTED COPY 
contract research organization
REDACTED COPY 
contract research organization
Suicide Severity Rating Scale
REDACTED COPY 
Suicide Severity Rating Scale
Data Analysis Plan
REDACTED COPY 
Data Analysis Plan
electrocardiogram
REDACTED COPY 
electrocardiogram
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Behavior Rating Inventory of Executive Function
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Behavior Rating Inventory of Executive Function®
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®-Preschool Version
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-Preschool Version
contract research organization
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contract research organization
Suicide Severity Rating Scale
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Suicide Severity Rating Scale
Data Analysis Plan
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Data Analysis Plan
electrocardiogram
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electrocardiogram
electronic 
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electronic C
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Case 
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ase 
electroencephalogram
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electroencephalogram
enzyme
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enzyme
Full Analysis Set
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Full Analysis Set
HRQoL
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HRQoL
ICH
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ICH
IDMC
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IDMC
IEC
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IEC


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 11of 97
IXRS
interactive voice/web response system
LCM
lacosamide
LFT
liver function test
LSM
least squares mean
MedDRA®
Medical Dictionary for Regulatory Activities
PD
pharmacodynamic(s)
PedsQL™
Pediatric Quality of Life Inventory
PET
polyethylene terephthalate
PK
pharmacokinetic(s)
PK-PPS
Pharmacokinetic Per-Protocol Set
PPS
Per Protocol Set
PT
preferred term
QTc
corrected QT interval
RDC
remote data capture
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
SOC
system organ class
SOP
standard operating procedure
SS
Safety Set
TAD
time after dose
TEAE
treatment-emergent adverse event
ULN
upper limit of normal
WHO
World Health Organization
VNS
vagus nervestimulation
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Statistical Analysis Plan
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Statistical Analysis Plan
standard deviation
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standard deviation
system organ class
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system organ class
standard operating procedure
REDACTED COPY 
standard operating procedure
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system organ class
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system organ class
standard operating procedure
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standard operating procedure
Safety Set
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Safety Set
time after dose
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time after dose
treatment
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treatment
upper limit of normal
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upper limit of normal


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 12of 97
1
SUMMARY
SP0969 is a Phase 3, multicenter, double-blind, randomized, placebo-controlled, 
parallel-group study to evaluate the efficacy and safety of lacosamide (LCM) as adjunctive 
therapy in subjects with epilepsy ≥4years to <17years of age with partial-onset seizures.
A total of approximately 300subjects with uncontrolled partial-onset seizures will be 
enrolled at approximately 149sites in 
 
 and other regions as deemed necessary. The maximum duration of a 
subject’s study participation is up to 36 weeks. The maximum duration of study medication 
administration is 24weeks.
The study is comprised of the following: an8-week Baseline Period;a 6-week Titration 
Period (with study medication dosing flexibility allowed based on tolerability) to achieve a 
target dose for the Maintenance Period (LCM8mg/kg/day to 12mg/kg/day for subjects 
weighing <30kg, LCM 6mg/kg/day to 8mg/kg/day for subjects weighing ≥30kg to <50kg, 
and LCM 300mg/day to 400mg/day for subjects weighing ≥50kg, or matching placebo);a 
10-week Maintenance Period at the dose of study medication achieved on the finalday of the 
Titration Period; and then a 4-week blinded Transition Period(for subjects who plan to enter 
the open-label extension study [EP0034])or a blinded Taper Period(2to 4weeks)followed 
by a 30-day Safety Follow-Up Period (for subjects who will not be entering EP0034).
The assessment of efficacy is based on partial-onset seizure frequency. The primary efficacy 
variable is the change in partial-onset seizure frequency per 28days from Baseline to the 
Maintenance Period. Secondary and other efficacy variables will allow further exploration of 
the effect of LCM on partial-onset seizure frequency, global impressions of changes, quality 
of life assessments (Pediatric Quality of Life Inventory [PedsQL™]), and health care resource 
use. Plasma concentrations of LCM and concomitant antiepileptic drugs (AEDs) will be 
obtained in order to develop a population PK model of LCM, to investigate the effect of 
LCM on the steady-state plasma concentrations of concomitant AEDs, and to investigate the 
correlation between LCM plasma concentrations and efficacy/or safety.
Safety will be evaluated based on the occurrence of adverse events (AEs) reported 
spontaneously by the subject and/or caregiver or observed by the investigator; subject 
withdrawals due to AEs; the results of periodic clinical laboratory, electrocardiogram (ECG), 
and vital sign monitoring; physical and neurological examinations;behavioral assessments 
(Achenbach Child Behavior Checklist [CBCL]); and cognitive function assessments 
(Behavior Rating Inventory of Executive Function
® [BRIEF®]/BRIEF
®-Preschool Version 
[BRIEF®-P]).
2
INTRODUCTION
Epilepsyis 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, 
REDACTED COPY 
a blinded Taper Period
REDACTED COPY 
a blinded Taper Period
(for subjects who will not be entering EP0034).
REDACTED COPY 
(for subjects who will not be entering EP0034).
 is based on partial
REDACTED COPY 
 is based on partialonset seizure frequency
REDACTED COPY 
onset seizure frequency
onset seizure frequency
REDACTED COPY 
onset seizure frequency
 and other efficacy
REDACTED COPY 
 and other efficacy
onset seizure frequency
REDACTED COPY 
onset seizure frequency
y of Life Inventory [PedsQL
REDACTED COPY 
y of Life Inventory [PedsQL
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. The maximum duration of a 
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. The maximum duration of a 
weeks. The maximum duration of study medication 
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weeks. The maximum duration of study medication 
Titration 
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Titration 
tolerability
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tolerability)
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)to achieve 
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to achieve 
/kg/day for subjects 
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/kg/day for subjects 
 for subjects weighing 
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 for subjects weighing ≥30kg to <50kg, 
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≥30kg to <50kg, 
≥50kg, or matching placebo)
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≥50kg, or matching placebo)
medication achieved on the 
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medication achieved on the 
Transition Period
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Transition Period(for subjects who plan to en
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(for subjects who plan to en
a blinded Taper Period
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a blinded Taper Period
(for subjects who will not be entering EP0034).
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(for subjects who will not be entering EP0034).
onset seizure frequency
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onset seizure frequency
onset seizure frequency
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onset seizure frequency
 and other efficacy
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 and other efficacy variables will allow further exploration of 
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 variables will allow further exploration of 
 and other efficacy variables will allow further exploration of 
 and other efficacy
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 and other efficacy variables will allow further exploration of 
 and other efficacy
onset seizure frequency
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onset seizure frequency
y of Life Inventory [PedsQL
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y of Life Inventory [PedsQL
CM and concomitant antiepileptic drugs (AEDs) will be 
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CM and concomitant antiepileptic drugs (AEDs) will be 
population PK model of L
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population PK model of L
y-state plasma concentrations of concomitant AEDs, and 
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y-state plasma concentrations of concomitant AEDs, and 
correlation between LCM plasma concentrations and efficacy
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correlation between LCM plasma concentrations and efficacy
 will be evaluated based on the o
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 will be evaluated based on the o
 the subject and/or caregiver or observed by
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 the subject and/or caregiver or observed by
withdrawals due to AEs; the results of periodic clinical laboratory
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withdrawals due to AEs; the results of periodic clinical laboratory
and vital sign monitoring; phy
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and vital sign monitoring; phy
(Achenbach Child Behavior Checklist [CBCL
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(Achenbach Child Behavior Checklist [CBCL
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(Behavior Rating Inventory
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(Behavior Rating Inventory
EF
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EF®
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®-
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-P])
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P])
Epilepsy
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Epilepsy
40
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40


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 13of 97
classification systems for seizure types and syndromes, gaps in information about epilepsy, 
and general recommendations (Institute of Medicine, 2012). Several neweroptions for the 
medical treatment of epilepsy have been introduced, including novel AEDs and vagus nerve 
stimulation (VNS). The classification of epilepsies in children was described in 1 989 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). Therefore, a need 
remains for AEDs with improved effectiveness and tolerability (Sander, 1998).
Among the newer AEDs, only 5(gabapentin, lamotrigine, oxcarbazepine, topiramate, and 
levetiracetam) have successfully demonstrated efficacy as adjunctive therapy in children with 
difficult to treat partial-onset seizures (Glauser et al, 2006; Glauser et al, 2000; Appleton et 
al, 1999; Duchowny et al, 1999; Elterman etal, 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). 
Lacosamide (VIMPAT®; SPM927; previously referred to as harkoseride; (R)-2-acetamido-
N-benzyl-3-methoxypropionamide, ADD 234037) belongs to a novel class of functionalized 
amino acids. It has minimal protein binding and effect on cytochrome P450 enzymesystem 
function (reducing the risk of drug-drug interactions), high oral bioavailability, and a half-life 
of approximately 13 hours (in adults), which allows a twice daily (bid) dose regimen. It also 
displays dose-proportional PK following administration over a range of doses up to 800mg in 
adults.
Lacosamide has been approved as adjunctive therapy in the treatment of partial-onset seizures 
in patients 17years of age and older in the United States (tablets, oral solution, and solution 
for intravenous [iv] infusion) and in patients 16years of age and older in the European Union 
(partial-onset seizures with or without secondary generalization) (tablets, oral solution, and 
solution for iv infusion). The oral solution (also referred to as syrup) is a formulation suitable 
for administration to children. Bioequivalence has been shown between the tablet and oral 
solution formulations, comparing 2tablets of LCM100mg and the oral solution containing 
LCM200mg, after single-dose administration in healthy subjects.The PK of LCM and 
SPM12809 (major LCM metabolite in humans) in plasma, urine, and saliva were identical or 
very similar after single oral doses of LCM 200mg administered as tablets or as oral solution.
In the clinical development program for LCM, safety and tolerability of multiple doses of up 
to LCM400mg bid (LCM800mg/day) were evaluated in approximately 800unique 
volunteers who received LCM in Phase 1 studies. The safety and efficacy of LCM has also 
been evaluated in Phase 2/3 studies as adjunctive oral therapy in over 1300adult subjects 
with partial-onset seizures and as oral monotherapy in over 2400adult subjects in other 
indications (neuropathic pain, osteoarthritis, fibromyalgia, and migraine prophylaxis). In 
REDACTED COPY 
al, 1999). Despite the availability
REDACTED COPY 
al, 1999). Despite the availability
more than 25% of pediatric patients have inadequate seizure control on currently
REDACTED COPY 
more than 25% of pediatric patients have inadequate seizure control on currently
AEDs or experience significant adverse drug effects (Hadjiloizou and Bourgeois, 2007
REDACTED COPY 
AEDs or experience significant adverse drug effects (Hadjiloizou and Bourgeois, 2007
927; previously
REDACTED COPY 
927; previously referred to as harkoseride; (R)
REDACTED COPY 
 referred to as harkoseride; (R)
927; previously referred to as harkoseride; (R)
927; previously
REDACTED COPY 
927; previously referred to as harkoseride; (R)
927; previously
propionamide, ADD
REDACTED COPY 
propionamide, ADD234037) belongs to a novel class of functionalized 
REDACTED COPY 
234037) belongs to a novel class of functionalized 
amino acids. It has minimal protein binding and effect on cy
REDACTED COPY 
amino acids. It has minimal protein binding and effect on cy
drug interactions), high oral bioavailability
REDACTED COPY 
drug interactions), high oral bioavailability
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s, including mechanism of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s, including mechanism of 
, 1998). However, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, 1998). However, 
 available AEDs or 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 available AEDs or 
experience significant adverse drug effects (CHMP/EWP/566/98, 2010). Therefore, a need 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
experience significant adverse drug effects (CHMP/EWP/566/98, 2010). Therefore, a need 
 (Sander, 1998).
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 (Sander, 1998).
apentin, lamotrigine, oxcarbazepine, topiramate, and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
apentin, lamotrigine, oxcarbazepine, topiramate, and 
 demonstrated efficacy as adjunctive therapy
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 demonstrated efficacy as adjunctive therapy
Glauser et al, 2006; Glauser et al, 2000; 
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Glauser et al, 2006; Glauser et al, 2000; 
al, 1999). Despite the availability
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
al, 1999). Despite the availability
more than 25% of pediatric patients have inadequate seizure control on currently
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
more than 25% of pediatric patients have inadequate seizure control on currently
AEDs or experience significant adverse drug effects (Hadjiloizou and Bourgeois, 2007
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
AEDs or experience significant adverse drug effects (Hadjiloizou and Bourgeois, 2007
 referred to as harkoseride; (R)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 referred to as harkoseride; (R)
234037) belongs to a novel class of functionalized 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
234037) belongs to a novel class of functionalized 
amino acids. It has minimal protein binding and effect on cy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
amino acids. It has minimal protein binding and effect on cy
drug interactions), high oral bioavailability
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
drug interactions), high oral bioavailability
 13 hours (in adults), which allows a twice dail
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 13 hours (in adults), which allows a twice dail
proportional PK following administration 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
proportional PK following administration 
Lacosamide has been approved as adjunctive therapy in the treatment of partial
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Lacosamide has been approved as adjunctive therapy in the treatment of partial
ars of age and older in the United States (tablets, oral solution, and solution 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ars of age and older in the United States (tablets, oral solution, and solution 
for intravenous [iv] infusion) and in patients 16
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for intravenous [iv] infusion) and in patients 16
onset seizures with or without secondary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizures with or without secondary
solution for iv infusion). The oral solution (also referred to as s
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
solution for iv infusion). The oral solution (also referred to as s
for administration to children. Bioequivalence has been shown between the tablet and oral 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
for administration to children. Bioequivalence has been shown between the tablet and oral 
solution formulations, comparing 2
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solution formulations, comparing 2
200mg, after single
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200mg, after single
SPM
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SPM12809 (major L
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12809 (major L
very
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very similar after single oral doses of LCM
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 similar after single oral doses of LCM
very similar after single oral doses of LCM
very
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very similar after single oral doses of LCM
very
In the clinical development program for LCM, safety
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In the clinical development program for LCM, safety


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 14of 97
addition, LCM solution for infusion was evaluated as short-term replacement therapy in a 
subset of subjects with partial-onset seizures (220 patients) who were receiving adjunctive 
LCM tablets.
Three double-blind, placebo-controlled, multicenter studies (SP667, SP754, and SP755) in 
1308adult subjects, aged 16to 70years, established the efficacy of oral LCM as adjunctive 
therapy (1to 3concomitant AEDs) in subjects with difficult to control partial-onset seizures. 
In these studies, LCM was initiated at a dose of 100mg/day (in 2divided doses) and escalated 
to the randomized dose (LCM200mg/day, LCM400mg/day, or LCM600mg/day) in 
LCM100mg/day per week increments.
When oral LCM was administered as adjunctive therapy at doses up to LCM 600mg/day in 
the 3 double-blind, placebo-controlled, multicenter studies in subjects with partial-onset 
seizures, the most frequently reported treatment-emergent adverse events (TEAEs) were 
central nervous system- and gastrointestinal-associated events. A dose relationship was seen 
for the most frequently reported common TEAEs, including dizziness, nausea, and diplopia. 
The nature and frequency of AEs were comparable to adjunctive therapy with other marketed 
AEDs. Safety evaluations support the further development of LCM as an AED.
Pellock et al have recently conducted a systematic review of AEDs used in the treatment of 
partial-onset seizures (Bourgeois and Goodkin, 2012; Pellock et al, 2012).The AEDs that 
were shown to be superior to placebo for the adjunctive treatment of partial-onset seizures in 
adult clinical studies were also shown to be superior to placebo for adjunctive treatment of 
partial-onset seizures in thepediatric clinical studies (subjects >2years of age)in which they 
were investigated. Theefficacy and safety of LCM observed in clinical studies in adultsand 
preclinical data, as well as many additional attributes of LCM, render the drug appropriate to 
investigate in pediatric subjects. These attributes include predictable and linear PK, lack of 
drug-drug interactions, easy twice-daily dosing, and the availability of 3 different types of 
formulations in multiple strengths (allowing for flexibility indose range and individualizing 
treatment).
Lacosamide is being evaluated in pediatric subjects 1 month to 17 years of age in 3studies: 
SP847(open-label, Phase2, safety, tolerability, and PK study), SP848(open-label long-term 
safety study),and SP1047(PK study for subjects prescribed LCM).In SP847 and SP848, 
subjectswith uncontrolled partial-onset seizures receive LCM oral solution at doses up to 
12mg/kg/day based on tolerability. In SP1047, subjects with epilepsy receive LCM oral 
tablets (50mg, 100mg, 150mg,or 200mg), or LCM oral solution (LCM10mg/mL) that they 
had been prescribed for epilepsy and brought with them to the clinic for dosing. Preliminary 
data havenot demonstratedany clinically relevant changes in vital signs, in ECGs, or in 
clinical laboratory values; or evidence of cardiac-related treatment-emergent AEsorbody 
weight changes. PreliminaryPKdatasuggest that exposure-response in pediatric subjects 
2years to 17years of ageand adult subjects treated with LCM will be similar.
SP0969 is a Phase 3, multicenter, double-blind, randomized, placebo-controlled, 
parallel-group study to evaluate the efficacy and safety of LCM (LCM8mg/kg/day to 
12mg/kg/day for subjects weighing<30kg, LCM6mg/kg/day to 8mg/kg/day for subjects 
weighing ≥30kg to <50kg, and LCM300mg/day to 400mg/day for subjects weighing ≥50kg, 
REDACTED COPY 
stematic review of AEDs used in the treatment of 
REDACTED COPY 
stematic review of AEDs used in the treatment of 
(Bourgeois and Goodkin, 2012; Pellock et al, 2012).
REDACTED COPY 
(Bourgeois and Goodkin, 2012; Pellock et al, 2012).
for the adjunctive treatment of partial-
REDACTED COPY 
for the adjunctive treatment of partial-
clinical studies were also shown to be superior to placebo 
REDACTED COPY 
clinical studies were also shown to be superior to placebo 
pediatric clinical studies (subjects 
REDACTED COPY 
pediatric clinical studies (subjects 
and safety
REDACTED COPY 
and safetyof LCM observed in clinical 
REDACTED COPY 
of LCM observed in clinical 
 additional attributes of L
REDACTED COPY 
 additional attributes of L
investigate in pediatric subjects. These attributes include predictable and linear PK, lack of 
REDACTED COPY 
investigate in pediatric subjects. These attributes include predictable and linear PK, lack of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
es) and escalated 
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es) and escalated 
600mg/day
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600mg/day
ticenter studies in subjects with partial-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ticenter studies in subjects with partial-onset 
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onset 
(TEAEs) were 
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(TEAEs) were 
-associated events. A dose relationship was seen 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-associated events. A dose relationship was seen 
 reported common TEAEs, including dizziness, nausea, and diplopia. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 reported common TEAEs, including dizziness, nausea, and diplopia. 
 of AEs were comparable to adjunctive therapy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of AEs were comparable to adjunctive therapy with other marketed 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 with other marketed 
 of AEs were comparable to adjunctive therapy with other marketed 
 of AEs were comparable to adjunctive therapy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of AEs were comparable to adjunctive therapy with other marketed 
 of AEs were comparable to adjunctive therapy
CM as an AED.
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CM as an AED.
stematic review of AEDs used in the treatment of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
stematic review of AEDs used in the treatment of 
(Bourgeois and Goodkin, 2012; Pellock et al, 2012).
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(Bourgeois and Goodkin, 2012; Pellock et al, 2012).
for the adjunctive treatment of partial-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
for the adjunctive treatment of partial-
clinical studies were also shown to be superior to placebo 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
clinical studies were also shown to be superior to placebo 
pediatric clinical studies (subjects 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
pediatric clinical studies (subjects 
of LCM observed in clinical 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
of LCM observed in clinical 
 additional attributes of L
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 additional attributes of L
investigate in pediatric subjects. These attributes include predictable and linear PK, lack of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
investigate in pediatric subjects. These attributes include predictable and linear PK, lack of 
daily
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
daily dos
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 dos
daily dos
daily
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daily dos
daily
formulations in multiple strengths (allowing for flexibility
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
formulations in multiple strengths (allowing for flexibility
Lacosamide is being evaluated in pediatric subjects 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Lacosamide is being evaluated in pediatric subjects 
label, Phase
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label, Phase2
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2, 
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, safet
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safet
and SP1047
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and SP1047(PK study
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(PK study
uncontrolled partial
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uncontrolled partial
 based on tolerability
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 based on tolerability
(50mg, 100
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(50mg, 100
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had been prescribed 
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had been prescribed 
have
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havenot 
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not 
clinical laboratory
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clinical laboratory
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weight changes. Preliminary
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weight changes. Preliminary
2
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2ye
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ye


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 15of 97
or matching placebo) as adjunctive therapy in subjects with epilepsy ≥4years to <17years of 
age with uncontrolled partial-onset seizures.
3
STUDY OBJECTIVES
The primary objective of this study is to evaluate the efficacy of LCM administered 
concomitantly with 1 to ≤3 AEDs in subjectswith epilepsy ≥4years to <17years of age who 
currently have uncontrolled partial-onset seizures.
The secondary objective is to evaluate the safety and tolerability of LCM in subjects ≥4years 
to <17years of age.
An additional objective is to evaluate the PK of LCM in subjects ≥4years to <17years of 
age.
4 
STUDY VARIABLES
4.1
Efficacy variables
The assessment of efficacy is based on partial-onset seizure frequency.
4.1.1
Primary efficacy variable
The primary efficacy variable is the change in partial-onset seizure frequency per 28days 
from Baseline to the Maintenance Period.
4.1.2
Secondary efficacy variables
The secondary efficacy variables are described below:
Proportion of responders, where a responder is a subject experiencing a 50% or greater 
reduction in partial-onset seizure frequency from Baseline to the Maintenance Period
Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or >75% reduction in 
partial-onset seizure frequency from Baseline to the end of Maintenance Period
Change in partial-onset seizure frequency per 28days from Baseline to the entire 
treatment (ie, Titration+Maintenance Periods)
Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or >75% reduction in 
partial-onset seizure frequency from Baseline to the entire treatment (ie, 
Titration+Maintenance Periods)
Proportion of subjects experiencing no change in partial-onset seizure frequency (between 
<25%reduction and <25% increase) from Baseline to the entire treatment (ie, 
Titration+Maintenance Periods)
Proportion of subjects experiencing an increase in partial-onset seizure frequency of 
≥25% from Baseline to the entire treatment (ie, Titration+Maintenanc e Periods)
Change in partial-onset seizure frequency per 28days from Baseline to the entire 
treatment(ie, Titration+Maintenance Periods) by seizure type
Proportion of seizure-free days during the Maintenance Period for subjects who entered 
the Maintenance Period
REDACTED COPY 
 variable is the change in partia
REDACTED COPY 
 variable is the change in partial-
REDACTED COPY 
l-onset seizure frequency
REDACTED COPY 
onset seizure frequency
 variables
REDACTED COPY 
 variables
 variables are described below:
REDACTED COPY 
 variables are described below:
Proportion of responders, where a responder is a subject experiencing a 50% or greater 
REDACTED COPY 
Proportion of responders, where a responder is a subject experiencing a 50% or greater 
onset seizure frequency
REDACTED COPY 
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ye
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
years 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ars 
ye
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years of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ars of 
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizure frequency
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizure frequency
 variables are described below:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 variables are described below:
Proportion of responders, where a responder is a subject experiencing a 50% or greater 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of responders, where a responder is a subject experiencing a 50% or greater 
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizure frequency
Proportion of subjects experiencing a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of subjects experiencing a 
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizure frequency from Baseline to the end of Maintenance Period
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 from Baseline to the end of Maintenance Period
onset seizure frequency from Baseline to the end of Maintenance Period
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizure frequency from Baseline to the end of Maintenance Period
onset seizure frequency
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
treatment (ie, Titration+Maintenance Periods)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
treatment (ie, Titration+Maintenance Periods)
Proportion of subjects experiencing a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of subjects experiencing a 
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizure frequency
Titration+Maintenance Periods)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Titration+Maintenance Periods)
Proportion of subjects experiencing no change in partial-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of subjects experiencing no change in partial-
<25%
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<25%reduction and <25%
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
reduction and <25%
Titration+Maintenance Periods)
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Titration+Maintenance Periods)

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Proportion of subjects experiencing an increase in partial-
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Proportion of subjects experiencing an increase in partial-


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 16of 97
Proportion of subjects who achieved “seizure-free” status (yes/no) for subjects who 
completed the Maintenance Period
4.1.3
Other efficacy variables
Other efficacy variables to be examined include:
Clinical Global Impression of Change at the end of the Maintenance Period
Caregiver’s Global Impression of Change at the end of the Maintenance Period
Qualityof life assessments (PedsQL)
Health care resource use (concomitant AEDs, medical procedures, health care provider 
consultations including hospitalizations not foreseen by the protocol)
4.2 
Safety variables
4.2.1
Primary safety variables
Safety and tolerability willbe assessed using the following primary variables:
Adverse events reported spontaneously by the subject and/or caregiver (including 
parent/legal guardian) or observed by the investigator
Subject withdrawals due to AEs
4.2.2
Other safety variables
Changes in hematology, clinical chemistry, and endocrinology parameters
Changes in 12-lead ECGs
Changes in vital sign measurements (ie, blood pressure [BP] and pulserate)
Physical and neurological examination findings
Changes in body weight, height, and calculated bodymass index 
Behavioral assessments (Achenbach CBCL/1½-5 or CBCL/6-18)
Cognitive function assessments (BRIEF-P/BRIEF)
4.3
Pharmacokinetic and pharmacodynamic variables
Plasma concentrations of LCM and concomitant AEDs will be obtained in order to:
Develop a population PK model of LCM
Investigate the effect of LCM on the steady-state plasma concentrations of concomitant 
AEDs
Investigate the correlation between LCM plasma concentrations and efficacy or safety
REDACTED COPY 
y the investigator
REDACTED COPY 
y the investigator
, clinical chemistry
REDACTED COPY 
, clinical chemistry
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Health care resource use (concomitant AEDs, medical procedures, health care provider 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Health care resource use (concomitant AEDs, medical procedures, health care provider 
be assessed using the following primary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
be assessed using the following primary variables:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 variables:
be assessed using the following primary variables:
be assessed using the following primary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
be assessed using the following primary variables:
be assessed using the following primary
 the subject and/or caregiver (including 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 the subject and/or caregiver (including 
, clinical chemistry
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, clinical chemistry, and endocrinology
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, and endocrinology
Changes in vital sign measurements (ie, blood pressure [BP] and pulse
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Changes in vital sign measurements (ie, blood pressure [BP] and pulse
sical and neurological examination findings
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sical and neurological examination findings
y weight, height, and calculated body
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y weight, height, and calculated body
Behavioral assessments (Achenbach CBCL/1½
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Behavioral assessments (Achenbach CBCL/1½
Cognitive function assessments (BRIEF-
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Cognitive function assessments (BRIEF-
Pharmacokinetic and pharmacody
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Pharmacokinetic and pharmacody
Plasma concentrations of L
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Plasma concentrations of L
Develop a 
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Develop a 
Investigate t
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Investigate t
AEDs
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AEDs

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


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 17of 97
5
STUDY DESIGN
5.1 
Study description
SP0969 is a Phase 3, multicenter, double-blind, randomized, placebo-controlled, 
parallel-group study to evaluate the efficacy and safety of LCM (LCM8mg/kg/day to 
12mg/kg/day [oral solution] for subjects weighing<30kg, LCM 6mg/kg/day to 8mg/kg/day 
[oral solution] for subjectsweighing ≥30kg to <50kg, and LCM 300mg/day to 400mg/day 
[tablets] for subjects weighing ≥50kg, or matchingplacebo) as adjunctive therapy in subjects 
with epilepsy ≥4years to <17years of age with uncontrolled partial-onset seizures.Subjects 
weighing≥50kg who are unable or unwilling to swallow tabletsmay receive LCM oral 
solution; however, they are not permitted to exceed the maximum dose of LCM400mg/day.
The study consists of the followingperiods:
Baseline Period
Subjects with uncontrolled partial-onset seizures will be enrolled into an8-week Baseline 
Period. At the end of the Baseline Period, subjects will be randomized in a double-blind 
manner to 1 of 2parallel treatment arms: LCM or placebo in a 1:1 ratio.
Titration Period
Eligible subjects will entera 6-week Titration Period (with study medication dosing 
flexibility allowed based on tolerability)to achievethe target Maintenance Period dose 
(LCM8mg/kg/day to 12mg/kg/day for subjects weighing<30kg, LCM 6mg/kg/day to 
8mg/kg/day for subjects weighing≥30kg to <50kg, and LCM300mg/day to 400mg/day for 
subjects weighing≥50kg, or matchingplacebo). For subjects who require study medication 
dosing flexibility based on tolerability, there is no limit to the number of back titration steps 
or dose holds allowed and all are at the investigator’s discretion ; however, subjects must 
remain on the back-titrated dose for ≥3days before the dose may be increased. Subjects must 
achieve the minimum target dose for their body weight category for the final 3daysof the 
Titration Period to be eligible for entry into the Maintenance Period. If it becomes apparent 
that a subject will not be able to reach the minimum target dose, then the subject should be 
withdrawn from the study and enter the Taper Period. 
The recommended LCM (or matching placebo) dosing during the Titration Period to achieve 
thetarget doses for the Maintenance Periodis provided in Table 7‒1; subjects are required to 
comply with Week 1 dosing as shown.Subsequent to Week1, dosing flexibility based on 
tolerability is permitted as described in Table7‒2.
Maintenance Period
Subjects who achieved at least the minimum target study medication (LCM or matching 
placebo) dose for the final 3days of the Titration Period will enter a 10-week Maintenance 
Period on the study medication dose achieved on the finaldayof the Titration Period. 
Lacosamide dose(or matching placebo) will remain stable throughout the Maintenance 
Period. Subjects who complete the Maintenance Period and plan to participate in the 
open-label extension study (EP0034) will enter the blinded Transition Period. Subjects who 
require a change in dose during the Maintenance Period will be withdrawn and enter the 
REDACTED COPY 
Titration Period 
REDACTED COPY 
Titration Period (
REDACTED COPY 
(
achieve
REDACTED COPY 
achieve
 for subjects 
REDACTED COPY 
 for subjects weigh
REDACTED COPY 
weigh
≥30kg to <50kg, a
REDACTED COPY 
≥30kg to <50kg, a
matching
REDACTED COPY 
matchingplacebo)
REDACTED COPY 
placebo)
 based on tolerability
REDACTED COPY 
 based on tolerability, there is no limit to the number of back titration steps 
REDACTED COPY 
, there is no limit to the number of back titration steps 
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y in subjects 
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y in subjects 
ubjects 
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ubjects 
CM oral 
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CM oral 
400mg/day
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400mg/day
onset seizures will be enrolled into a
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onset seizures will be enrolled into an8
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n8
Period. At the end of the Baseline Period, subjects will be randomized in a double
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Period. At the end of the Baseline Period, subjects will be randomized in a double
parallel treatment arms: LCM or placebo in a 1:1 ratio.
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parallel treatment arms: LCM or placebo in a 1:1 ratio.
(
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(with 
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with study
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study
the target Maintenance Period dose 
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the target Maintenance Period dose 
weigh
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weighing
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ing
≥30kg to <50kg, a
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≥30kg to <50kg, a
placebo)
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placebo)
, there is no limit to the number of back titration steps 
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, there is no limit to the number of back titration steps 
dose holds allowed and all are at the investigator’s discretion; 
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dose holds allowed and all are at the investigator’s discretion; 
-titrated dose for 
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-titrated dose for ≥3
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≥3day
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day
achieve the minimum target dose for their bod
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achieve the minimum target dose for their bod
to be eligible for entry
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to be eligible for entry
that a subject will not be able to reach the minimum target dose
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that a subject will not be able to reach the minimum target dose
withdrawn from the study
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withdrawn from the study
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and enter the Taper Peri
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and enter the Taper Peri
The recommended LCM (or matching placebo) dosing during the Titration Period 
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The recommended LCM (or matching placebo) dosing during the Titration Period 
target doses for the Maintenance Period
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target doses for the Maintenance Period
 with Week
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 with Week
tolerability
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tolerability is permitted as described in 
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 is permitted as described in 
tolerability is permitted as described in 
tolerability
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tolerability is permitted as described in 
tolerability
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Maintenance Period
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Maintenance Period
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Subjects 
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Subjects 
placebo) dose for the final 3
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placebo) dose for the final 3
Period on the 
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Period on the 


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 18of 97
blinded Taper Period. Subjects who choose not to participate in EP0034 will also enter the 
Taper Period.
Transition Period
Subjects who complete the Maintenance Periodand plan to participate in the open-label 
extension study (EP0034)will enter a 4-week blinded Transition Period. Subjects randomized 
to LCM will maintain their Maintenance Period dose during theTransition Period.Subjects 
randomized to placebo will transition to LCM in a double-blind fashion in accordance with 
the schedule provided in Table 7‒4.
Taper Period
The blinded Taper Period(2to 4 weeks, depending on dose level achieved)is for subjects 
who will not be enteringthe open-label extension study (EP0034) for any of the following 
reasons:
Subject does not complete the Titration Period, the Maintenance Period, or the Transition 
Period.
Subject doesnot choose to enroll in the open-label extension study (EP0034) after 
completing the Maintenance Period or the Transition Period.
Taper of LCM may not be required for some subjects who discontinue study medication 
prematurely, depending on the treatment option selected by the investigator in consultation 
with the subject and/or parent/legal representative.
The dosing of study medication for the Taper Period is provided inTable7‒5.
Safety Follow-Up Period
There will be a 30-daySafety Follow-Up Period for subjects not entering the open-label 
extension study (EP0034).
Unscheduled visits can be conducted at the discretion of the investigator.
Detailedschedulesof study procedures are provided in Section5.2, and study schematic 
diagramsare included in Section5.3.
5.1.1 
Study duration per subject
Each subject’s participation in the study begins with an8-week Baseline Period. Each 
subject’s total duration of study medication administration is up to 24 weeks; this includes a 
6-week Titration Period, a 10-week Maintenance Period, and a 4-week Transition Period (for 
subjects who plan to enter the open-label extension study [EP0034]) anda Taper Period(2to 
4 weeks, depending on dose level achieved for subjects who will not be entering EP0034). 
The total study duration can be upto36 weeks, including the 30-daySafety Follow-Up 
Period. Both the total duration of study medication and the total study duration include the 
possibility of a subject who completes the Transition Period choosing not to participate in 
EP0034 and having to enter the Taper Period.
The end of the study is defined as the date of the last visit of the last subject in thestudy.
REDACTED COPY 
or the Transition Period
REDACTED COPY 
or the Transition Period
 not be required for some subjects who disconti
REDACTED COPY 
 not be required for some subjects who disconti
depending on the treatment option selected by
REDACTED COPY 
depending on the treatment option selected by
representative
REDACTED COPY 
representative
for the Taper Period 
REDACTED COPY 
for the Taper Period 
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accordance with 
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accordance with 
for subjects 
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for subjects 
 of the following 
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 of the following 
the Maintenance Period, or the Transition 
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the Maintenance Period, or the Transition 
label extension study
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label extension study
or the Transition Period
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or the Transition Period
 not be required for some subjects who disconti
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 not be required for some subjects who disconti
depending on the treatment option selected by
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depending on the treatment option selected by
representative
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representative.
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.
for the Taper Period 
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for the Taper Period 
y Follow
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y Follow-Up Period for subjects not entering the open
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-Up Period for subjects not entering the open
conducted at the discretion of the investigator.
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conducted at the discretion of the investigator.
of study
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of study
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 procedures 
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 procedures 
of study procedures 
of study
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of study procedures 
of study
included in Section
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included in Section
Study duration per subject
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Study duration per subject
Each subject’s participation in the study
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Each subject’s participation in the study
’s total duration of study
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’s total duration of study
week Titration Period, a 
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week Titration Period, a 
subjects who plan to enter 
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subjects who plan to enter 
weeks, depending on dose level achieved
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weeks, depending on dose level achieved
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The total study
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The total study
Period
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Period


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 19of 97
5.1.2
Planned number of subjects and sites 
A total ofapproximately 300subjects are planned to be randomized.
Stratification of subjects by age category is planned to ensure that an appropriate number of 
subjects will be included in each age range. The age categories are as follows:
At least 100 subjects ≥4years to <12years of age
At least 100 subjects ≥12 years to <17years of age
Approximately 149 sites are planned in order to recruit the required subjects; ad ditional sites 
will be added if deemed necessary. 
5.1.3
Anticipated regions and countries
The study will be conducted in the
,and the 
with the possibility to expand the study to other countries and regions if 
deemed necessary.
5.2
Schedule of studyassessments
Table 5-1,Table5-2, and Table 5-3present the tabular schedules of study procedures.
REDACTED COPY 
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sites are planned in order to recruit the required subjects; additional sites 
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sites are planned in order to recruit the required subjects; additional sites 
and the 
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and the 
 to other countries and regions if 
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 to other countries and regions if 
present the tabular schedules of study
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present the tabular schedules of study


UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 20of 97
Table5-1
Schedule of study assessments (Baseline Period, Titration Period, Maintenance Period, Early 
TerminationVisit, and Unscheduled Visits)
Assessments
Baseline Period 
(8weeks)
Treatment Period (16 weeks)
Titration Period (6 weeks)
Maintenance Period (10 weeks)
Visit
V1a
T1
V2
T2
V3
T3
V4
T4
V5 
V6
T5
V7
T6
V8b
ET
Unscheduled 
Visitc
Week in study
-8
-4
0  
1  
2
3
4
5
6
8
10 
12 
14 
16
Informed consent
X
Inclusion/exclusion criteria
X
X  X
Medical historyd
X
Seizure history
X
Concomitant medications
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
Concomitant AEDs
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
VNS assessment
e
X
X
X
X
X
X  
X
X
X  
X
Physical examination 
(complete)
X
X
X
X
Physical examination (brief)
X
X
X
X  
X
Tanner Stagef
X
X
X
Vital signs (BP and pulse rate, 
including orthostatic 
assessments) 
X
X
X
X
X
X  
X
X
X  
X
Body weight
g
X
Xg
X
X
X
X  
X
X
X  
X
Height
X
X
X
X
Head circumference
X
X
X
Neurological examination 
(complete)
X
X
X
X
Neurological examination 
(brief)
X
X
X
X  
X
ECG (12-lead)
h
X
X
X
X
X
X  
X
X
X
REDACTED COPY 
REDACTED COPY 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
REDACTED COPY 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
REDACTED COPY 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
X
X
REDACTED COPY 
X
X
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
X
X
REDACTED COPY 
X
X
REDACTED COPY 
REDACTED COPY 
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05
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05
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Maintenance Period, Early
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Maintenance Period, Early
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Maintenance Period (
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Maintenance Period (
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T5
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T5
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10 
12 
14 
16
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10 
12 
14 
16
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X
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X
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X
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X
X
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X
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X
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
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X
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 21of 97
Table5-1
Schedule of study assessments (Baseline Period, Titration Period, Maintenance Period, Early 
TerminationVisit, and Unscheduled Visits)
Assessments
Baseline Period 
(8weeks)
Treatment Period (16 weeks)
Titration Period (6 weeks)
Maintenance Period (10 weeks)
Visit
V1a
T1
V2
T2
V3
T3
V4
T4
V5 
V6
T5
V7
T6
V8b
ET
Unscheduled 
Visitc
Week in study
-8
-4
0  
1  
2
3
4
5
6
8
10 
12 
14 
16
Clinical chemistry/hematology
X
X
X
X
X
X
X
Endocrinology
X
X
X
Urinalysisi
X
X
X
X
X
X
X
Serum pregnancy testj
X
X
X
X
X
X
Urine pregnancy testj
X
X
X
Concomitant AED plasma 
concentrations
k
X
X
X
X
LCM plasma concentrationk
X
X
X
X
C-SSRSl
X
X
X
X
X
X  
X
X
X  
X
Clinical Global Impression of 
Change
X
X
Caregiver’s Global Impression 
of Change
X
X
Achenbach CBCLm
X
X
X
X
BRIEF-P/BRIEFn
X
X
X
PedsQLo
X
X
X
Contact IXRS
X
X
X
X
X
X  
X
X
X
Randomization
p
X
Dispense study medication
Xl
X
X
X
X  
X
X
X
Study medication return
X
X
X
X  
X
X
X
Subject diary
q
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
Withdrawal criteria
X  X  
X  
X
X
X
X
X
X
X
X
X  X
X
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
X
X
REDACTED COPY 
X
X
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
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05
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05
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Maintenance Period, Early
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Maintenance Period, Early
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Maintenance Period (
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Maintenance Period (
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T5
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T5
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10 
12 
14 
16
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10 
12 
14 
16
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X
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X
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X
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X
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X
X
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X
X
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X
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X
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X
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X
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X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
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X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
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UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 22of 97
Table5-1
Schedule of study assessments (Baseline Period, Titration Period, Maintenance Period, Early 
TerminationVisit, and Unscheduled Visits)
Assessments
Baseline Period 
(8weeks)
Treatment Period (16 weeks)
Titration Period (6 weeks)
Maintenance Period (10 weeks)
Visit
V1a
T1
V2
T2
V3
T3
V4
T4
V5 
V6
T5
V7
T6
V8b
ET
Unscheduled 
Visitc
Week in study
-8
-4
0  
1  
2
3
4
5
6
8
10 
12 
14 
16
AE reporting
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
Assessments of epilepsy 
surgery/VNS
X
Health care resource use
X
X
X
X
X
X  
X
X
X
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; BRIEF=Behavior Rating Inventory of Executive Function; BRIEF-P=Behavior Rating 
Inventory of Executive Function-Preschool Version; CBCL=Child Behavior Checklist; C-SSRS=Columbia-Suicide Severity Rating Scale; 
ECG=electrocardiogram; ET=Early Termination Visit; IXRS=interactive voice/web response system; LCM=lacosamide; PedsQL=Pediatric Quality of Life 
Inventory; T=Telephone Contact; V=Visit; VNS=vagus nerve stimulation
Note: For all visits shown in Table5-1, a time window of ±2 days relative to Visit2 (Baseline Period) is applicable.During the Treatment Period, each visit 
should occur at the end of the week indicatedin accordance with this time window.
aVisit1 (V1) may occur over more than 1 day; however, all results of Baseline/Visit 1 assessments should be available before randomization on Visit 2.
b At the end of Visit8, subjects who complete the Maintenance Period may be eligible to participate in an open-label extension study (EP0034). Subjects who 
planto enroll in the open-label extension study will proceed to a 4-week blinded Transition Period. Subjects who choose not to enter the open-label extension 
study or who do not complete the Maintenance Period will proceed to a blinded Taper Period (2to 4weeks, depending on dose level achieved).Taper of LCM 
may not be required for some subjects who discontinuestudy medication prematurely, depending on the treatment option selected by the investigator in 
consultation with the subject and/or parent/legal representative.
cIf an Unscheduled Visit is needed (eg, due to AE), then the assessments noted will be performed. Additional assessments may be performed at the 
investigator’s discretion. The C-SSRS will be completed at an Unscheduled Visit only if the visit is related to an AE.
dMedical history to include demographics (date of birth[where permitted], age group category,age in months and years, race, ethnicity, and gender).
eOnly applicable for subjects with an implanted VNS device.
fThe Tanner Stage will be performed only for subjects who are pubescent at Visit1 or who enter puberty during the course of the study.
gThe subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout the study.
hA 12-lead ECG (2interpretable recordings) will be performed prior to any blood draws and vital signs assessment. The subject should rest in the supine 
position for approximately 5 minutes before the recordingsand during the recordings,if possible. The recordings should be made 20 to 30 minutes apart.
iUrinalysis will be performed for subjects ≥5 years of age only.
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; BRIEF=Behavior Rating Inventory of Executive Function; BRIEF
REDACTED COPY 
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; BRIEF=Behavior Rating Inventory of Executive Function; BRIEF
Behavior Checklist; C
REDACTED COPY 
Behavior Checklist; C
ECG=electrocardiogram; ET=Early Termination Visit; IXRS=interactive voice/web response system; LCM=lacosamide; PedsQL=Pediatr
REDACTED COPY 
ECG=electrocardiogram; ET=Early Termination Visit; IXRS=interactive voice/web response system; LCM=lacosamide; PedsQL=Pediatr
VNS=vagus nerve stimulation
REDACTED COPY 
VNS=vagus nerve stimulation
a time window of ±2 days relative to Visit
REDACTED COPY 
a time window of ±2 days relative to Visit
in accordance with this time window.
REDACTED COPY 
in accordance with this time window.
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05
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05
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Maintenance Period, Early
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Maintenance Period, Early
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Maintenance Period (
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Maintenance Period (
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T5
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T5
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10 
12 
14 
16
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10 
12 
14 
16
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X  X  
X  
X
X
X
X
X
X
X
X
X  X  X  
X
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X
X  
X
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X
X  
X
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AE=adverse event; AED=antiepileptic drug; BP=blood pressure; BRIEF=Behavior Rating Inventory of Executive Function; BRIEF
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AE=adverse event; AED=antiepileptic drug; BP=blood pressure; BRIEF=Behavior Rating Inventory of Executive Function; BRIEF
Behavior Checklist; C
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Behavior Checklist; C
ECG=electrocardiogram; ET=Early Termination Visit; IXRS=interactive voice/web response system; LCM=lacosamide; PedsQL=Pediatr
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ECG=electrocardiogram; ET=Early Termination Visit; IXRS=interactive voice/web response system; LCM=lacosamide; PedsQL=Pediatr
a time window of ±2 days relative to Visit
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a time window of ±2 days relative to Visit
in accordance with this time window.
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in accordance with this time window.
1 (V1) may occur over more than 1 day; however, all results of 
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1 (V1) may occur over more than 1 day; however, all results of Baseline/Visit 1 assessments should be available before 
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Baseline/Visit 1 assessments should be available before 
, subjects who complete the Maintenance Period may be eligible to participate in an open
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, subjects who complete the Maintenance Period may be eligible to participate in an open
label extension study will proceed to a 
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label extension study will proceed to a 4-
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4-
study or who do not complete the Maintenance Period will proceed to a blinded Taper Period (
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study or who do not complete the Maintenance Period will proceed to a blinded Taper Period (
discontinue
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discontinuestudy 
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study 
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consultation with the subject and/or parent/legal representative.
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consultation with the subject and/or parent/legal representative.
If an Unscheduled Visit is needed (eg, due to AE), then the ass
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If an Unscheduled Visit is needed (eg, due to AE), then the ass
SSRS will be completed at an Unscheduled Visit 
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SSRS will be completed at an Unscheduled Visit 
Medical history to include demographics (
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Medical history to include demographics (date of birth
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date of birth
Only applicable for subjects with an implanted VNS
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Only applicable for subjects with an implanted VNS
The Tanner Stage will be performed only for subjects who are pubescent at Visit
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The Tanner Stage will be performed only for subjects who are pubescent at Visit
subject’s body weight at Baseline (V
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subject’s body weight at Baseline (V
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interpretable recordings) will be performed prior to any blood draws 
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interpretable recordings) will be performed prior to any blood draws 
position for approximately 5 minutes before the recording
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position for approximately 5 minutes before the recording
Urinalysis will be performed f
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Urinalysis will be performed for subjects 
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or subjects 
Urinalysis will be performed for subjects 
Urinalysis will be performed f
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Urinalysis will be performed for subjects 
Urinalysis will be performed f


UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 23of 97
jPregnancy tests will be performed for female subjects of childbearing potentialonly.
kBlood samples for analysis of concomitant AED plasma concentrations and/or LCM will be drawn along with clinical chemistry, hematology, and 
endocrinology samples, asapplicable.
lThe C-SSRS will be completed for all subjects ≥6years of age.The C-SSRS will be completed at an Unscheduled Visit only if the visit relatedto an AE.
mThe Achenbach CBCL: CBCL/1½ -5 for children 18months to 5 years and 11months of age, and CBCL/6-18 for children ≥6years to <17years of ageat 
Screening; to be completed by the parent(s)/legal representative(s) (estimated completion time 45minutes). For each subject, the same version of the scale that 
was completed at Visit2 (CBCL/1½ -5or CBCL/6-18) should be maintained for the duration of the study and shouldbe completed by the same parent/legal 
representative. The Achenbach CBCL will be used only in countries where a translated version is available.
nThe BRIEF-P should be used for subjects who are ≥2 years to <5 years of age at Visit2, and the BRIEF should be used for subjects who are ≥5 years of age at 
Visit2. The same version of the scale that was completed at Visit2 (BRIEF-P or BRIEF) should be maintained for each subject for the duration of the study.
The BRIEF-P and BRIEF will be used only in countries where a translatedversion is available.
oThe version of the PedsQL used at Visit2should be consistent with the subject’s ageat Visit2and should be maintained for each subject for the duration of 
the study.The PedsQL will be used only in countries where a translated version is available.
pAt the end of Visit2, subjects should take the first dose of study medication in the clinic.
qThe subject diary will be dispensed atVisit 1. At all subsequent visits,the subjectand/or legal representative(s)will be reminded to complete the diary on a 
daily basis. 
REDACTED COPY 
and/or legal representative(s)
REDACTED COPY 
and/or legal representative(s)
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05
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05
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Blood samples for analysis of concomitant AED plasma concentrations and/or LCM will be drawn along with clinical chemistry
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Blood samples for analysis of concomitant AED plasma concentrations and/or LCM will be drawn along with clinical chemistry, hematology
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, hematology
only 
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only if the visit related
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if the visit related
18 for children 
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18 for children ≥6
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≥6
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For each subject, the 
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For each subject, the 
should
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shouldbe completed by the same parent/legal 
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be completed by the same parent/legal 
, and the BRIEF should be used for subjects w
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, and the BRIEF should be used for subjects w
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P or BRIEF) should be maintained for each subject for 
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P or BRIEF) should be maintained for each subject for 
and should be maintained for each su
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and should be maintained for each su
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and/or legal representative(s)
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and/or legal representative(s)


UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 24of 97
Table5-2
Schedule of study assessments(Transition Period)
Assessment
Transition Period (4weeks)a
Visit
TV1 
TV2 
TV3 
TV4
Week in study
17a
18
19
20
Concomitant medications
X
X
X
X
Concomitant AEDs
X
X
X
X
VNS assessmentsb
X
X
X
X
Physical examination (complete)
X
Physical examination (brief)
X
X
X
Vital signs (BP and pulse rate, 
including orthostatic assessment)
X
X
X
X
Body weight
X
X
X
X
Neurologicalexamination (complete)
X
Neurological examination (brief)
X
X
X
12-lead ECGc
X
Clinical chemistry/hematology
X
Urinalysisd
X
Urinepregnancy test
e
X
Concomitant AED plasmaf
concentrations
X
LCM plasma concentration
f
X
C-SSRSg
X
X
X
X
Contact IXRS
X
X
X
X
Dispense study medication
X
X
X
Study medication return
X
X
X
X
Subject diaryh
X
X
X
X
Withdrawal criteria
X
X
X
X
AE reporting
X
X
X
X
Health care resource use
X
X
X
X
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; C-SSRS=Columbia-Suicide Severity Rating 
Scale; ECG=electrocardiogram; IXRS=interactive voice/web response system; LCM=lacosamide; 
TV=Transition Visit; VNS=vagus nerve stimulation
Note: For all visits shown in Table5-2, a window of ±2 days relative to Visit2 (Baseline Period) is applicable. 
Each visit should occur at the end of the week indicated in accordance with this time window.
aAt the end of Visit8, (Maintenance Period), subjects may be eligible to participate in an open-label extension 
study (EP0034). Subjects who plan to enroll in the open-label extension study will enter a 4-week blinded
Transition Period.
bOnly applicable for subjects with an implanted VNS device.
cA 12-lead ECG (2interpretable recordings) will be performed prior to any blood draws and vital signs 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
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X
X
X
X
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X
X
X
X
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X
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X
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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X
X
X
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
X
X
X
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X
X
X
X
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X
X
X
X
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X
X
X
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X
X
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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Withdrawal criteria
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Withdrawal criteria
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Health care resource use
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Health care resource use
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AE=adverse event; AED=antiepileptic drug; 
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AE=adverse event; AED=antiepileptic drug; 
Scale; ECG=electrocardiogram; IXRS=interactive voice/web response system; LCM=lacosamide; 
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Scale; ECG=electrocardiogram; IXRS=interactive voice/web response system; LCM=lacosamide; 
TV=Transition Visit; 
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TV=Transition Visit; 
Note: For all visits shown in 
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Note: For all visits shown in 
Each visit should occur at the end of the week indicated in accorda
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Each visit should occur at the end of the week indicated in accorda
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UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 25of 97
Table5-2
Schedule of study assessments(Transition Period)
Assessment
Transition Period (4weeks)a
Visit
TV1 
TV2 
TV3 
TV4
Week in study
17a
18
19
20
assessment. The subject should rest in the supine position for approximately 5 minutes before the ECG 
recording and during the recordings if possible. The recordings should be made 20 to 30 minutes apart.
dUrinalysis will be performed for subjects ≥5 years of age only.
ePregnancy tests will be performedfor female subjects of childbearing potential only.
fBlood samples for analysis of concomitant AED plasma concentrations and/or LCM will be drawn along with 
clinical chemistry, hematology, and endocrinology samples, as applicable.
gThe C-SSRS will be completed for all subjects ≥6years of age.
hThe subject diary will be returned at TV4. At all other visits, the subject and/or legal representative(s) will be 
reminded to complete the diary on a daily basis.
Table5-3
Schedule of study assessments (Taper Period and Safety 
Follow-Up Period)
Taper Perioda
(2to 4 weeks)
Safety Follow-Up Periodb
(30 days)
Assessment
Visit
T7c
Taper Visitd
Safety 
Follow-Up
Visit
Safety 
Follow-Up
Telephone 
Contact
Week in study
17
18, 19, or 20 
20, 21, or 22 
22, 23, or 24
Concomitant medications
X
X
X
X
Concomitant AEDs
X
X
X
X
VNS assessment
e
X
X
Physical examination (brief)
X
Physical examination (complete)
X
Vital signs (BP and pulse rate, 
including orthostatic assessment)
X
X
Body weight
X
X
Neurological examination (brief)
X
Neurological examination (complete)
X
ECG (12-lead)
f
X
Xg
Clinical chemistry/hematology
X
Xg
Endocrinology
X
Xg
Urinalysish
X
X
Serum pregnancy test
X
Xi
REDACTED COPY 
Taper Period
REDACTED COPY 
Taper Perioda
REDACTED COPY 
a
weeks)
REDACTED COPY 
weeks)
REDACTED COPY 
T7
REDACTED COPY 
T7
REDACTED COPY 
REDACTED COPY 
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samples for analysis of concomitant AED plasma concentrations and/or LCM will be drawn along with 
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samples for analysis of concomitant AED plasma concentrations and/or LCM will be drawn along with 
The subject diary will be returned at TV4. At all other visits, the subject and/or legal representative(s) will be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject diary will be returned at TV4. At all other visits, the subject and/or legal representative(s) will be 
 assessments (Taper Period and Safety
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 assessments (Taper Period and Safety
weeks)
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weeks)
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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T7
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T7c
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c
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17
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17
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Physical examination (brief)
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Physical examination (brief)
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Physical examination (complete)
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Physical examination (complete)
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Vital signs (BP and pulse rate, 
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Vital signs (BP and pulse rate, 
orthostatic assessment)
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orthostatic assessment)
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Body weight
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Body weight
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Neurological examination (brief)
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Neurological examination (brief)
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Neurological examination (complete)
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Neurological examination (complete)
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ECG (12
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ECG (12
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 26of 97
Table5-3
Schedule of study assessments (Taper Period and Safety 
Follow-Up Period)
Taper Perioda
(2to 4 weeks)
Safety Follow-Up Periodb
(30 days)
Assessment
Visit
T7c
Taper Visitd
Safety 
Follow-Up
Visit
Safety 
Follow-Up
Telephone 
Contact
Week in study
17
18, 19, or 20 
20, 21, or 22 
22, 23, or 24
Urine pregnancy test
Xi
C-SSRSj
X
X
Contact IXRS
X
Study medication return
X
Subject diaryk
X
X
Withdrawal criteria
X
X
AE reporting
X
X
X
X
Health care resource use
X
X
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; C-SSRS=Columbia-Suicide Severity Rating 
Scale; ECG=electrocardiogram; IXRS=interactive voice/web response system; LCM=lacosamide; T=Telephone 
Contact; VNS=vagus nerve stimulation
Note: The study week numbers provided are for subjects who complete the Maintenance Period and enter the 
Taper Period. The study week numbers provided do not apply to subjects who enter the Taper Period at other 
times.
aA blinded Taper Period (2 to 4 weeks, depending on dose achieved) will be required for subjects who 
discontinue study medication prematurely and for subjects who complete the Maintenance Period but choose 
not to enter the open-label extension study (EP0034). Taper of LCM may not be required for some subjects 
who discontinuestudy medication prematurely, depending on the treatment option selected by the investigator 
in consultation with the subject and or parent/legal representative.
bThe Safety Follow-Up Visit will occur 2 weeks (±2 days) after the final dose of study medication. The Safety 
Follow-Up Telephone Contact will occur 30days (-1/+3days) after the final dose of study medication.
cAtelephone contact (T7) will be conducted at the end of thefirst week of the Taper Period. 
dEach subject will have only 1 Taper Visit. The Taper Visit will be scheduled at the end of the Taper Period 
(Week 18, Week 19, or Week20, depending on dose level achieved; see Table 7‒5).A time window of 
±2days relative to Visit2 (Baseline Period) is applicable.
eOnly applicable for subjects with an implanted VNS device.
fA 12-lead ECG (2interpretable recordings) will be performed prior to any blood draws and vital signs 
assessment. The subject should rest in the supine position for approximately 5 minutes before therecording 
and during the recordings,if possible. The recordings should be made 20 to 30 minutes apart.
gThe assessment will only be required for subjects with an abnormal value (clinical chemistry, hematology, or 
endocrinology) or reading (ECG) at the previous clinic visit.
hUrinalysis will be performed for subjects ≥5 years of age only.
iPregnancy tests will be performed for female subjects of childbearing potential only. A serum pregnancy test 
will be performed at the Safety Follow-Up Visit only if blood is collected for other laboratory tests. If no 
blood is collectedfor other assessments, then aurine pregnancy test will be performed.
jThe C-SSRS will be completed for all subjects ≥6years of age.
REDACTED COPY 
X
X
REDACTED COPY 
X
X
X
X
REDACTED COPY 
X
X
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
AE=adverse event; AED=antiepileptic drug; BP=blood 
REDACTED COPY 
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; C
REDACTED COPY 
pressure; C
interactive voice/web response system; LCM=lacosamide; T=Telephone 
REDACTED COPY 
interactive voice/web response system; LCM=lacosamide; T=Telephone 
The study week numbers provided are for subjects who complete
REDACTED COPY 
The study week numbers provided are for subjects who complete
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Up
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Up
Telephone 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Telephone 
Contact
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Contact
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
18, 19, or 20 
20, 21, or 22 
22, 23, or 24
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
18, 19, or 20 
20, 21, or 22 
22, 23, or 24
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
X
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
pressure; C
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pressure; C
interactive voice/web response system; LCM=lacosamide; T=Telephone 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
interactive voice/web response system; LCM=lacosamide; T=Telephone 
The study week numbers provided are for subjects who complete
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The study week numbers provided are for subjects who complete
Taper Period. The study week numbers provided do not apply to subjects who enter the Taper Period at other 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Taper Period. The study week numbers provided do not apply to subjects who enter the Taper Period at other 
eeks, depending on dose achieved) will be required for subjects who 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
eeks, depending on dose achieved) will be required for subjects who 
discontinue study medication prematurely and for subjects who complete the Maintenance Period but choose 
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discontinue study medication prematurely and for subjects who complete the Maintenance Period but choose 
label extension study (EP0034).
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label extension study (EP0034).
medication 
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medication 
in consultation with the subject and or parent/legal representative.
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in consultation with the subject and or parent/legal representative.
Up Visit will occur 2 w
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Up Visit will occur 2 w
ephone Contact w
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ephone Contact w
ontact (T
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ontact (T7
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7
Each subject will have only 1 Taper Visit. T
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Each subject will have only 1 Taper Visit. T
18, Week
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18, Week
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days relative to Visit
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days relative to Visit
Only 
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Only applicable for subjects with an implanted VNS device.
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applicable for subjects with an implanted VNS device.
12
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12-
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-lead ECG (2
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lead ECG (2
assessment. The subject should rest in the supine position for approximately 5 minutes before the
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
assessment. The subject should rest in the supine position for approximately 5 minutes before the
and during the recording
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and during the recording
g
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gThe assessment will only be required for subjects w
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The assessment will only be required for subjects w
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UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 27of 97
Table5-3
Schedule of study assessments (Taper Period and Safety 
Follow-Up Period)
Taper Perioda
(2to 4 weeks)
Safety Follow-Up Periodb
(30 days)
Assessment
Visit
T7c
Taper Visitd
Safety 
Follow-Up
Visit
Safety 
Follow-Up
Telephone 
Contact
Week in study
17
18, 19, or 20 
20, 21, or 22 
22, 23, or 24
kAt T7, the subject and/or legal representative(s) will be reminded to complete the diary on  a daily basis. The 
subject diary will be returned at the Taper Visit.
5.3
Schematic diagram
An overall schematic diagram with successive panels for each body weight category (<30kg, 
≥30kg to <50kg, and ≥50kg) is provided inFigure5‒1. The schematic diagram for the 
Transition Period is provided in Figure5‒2.
REDACTED COPY 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Up
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Up
Telephone 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Telephone 
Contact
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Contact
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
18, 19, or 20 
20, 21, or 22 
22, 23, or 24
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
18, 19, or 20 
20, 21, or 22 
22, 23, or 24
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
At T7, the subject and/or legal representative(s) will be reminded to complete the diary on  a daily basis. The 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
At T7, the subject and/or legal representative(s) will be reminded to complete the diary on  a daily basis. The 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
with successive panels for each body
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with successive panels for each body weight category
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 weight category
with successive panels for each body weight category
with successive panels for each body
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with successive panels for each body weight category
with successive panels for each body
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The schematic diagram for the 
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The schematic diagram for the 


UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 28of 97
Figure 5‒1: SP0969 overall schematic diagram
V1
  T1
V2
V3-V4 and T2-T4
V5
V6 –V7 and T5-T6
V8
Taper Visit
Baseline Period
Titration Period
Maintenance Period 
Taper Perioda
(or Transition Period)b
12mg/kg/day or
placebo
10mg/kg/day or 
placebo
8mg/kg/day or 
placebo
9mg/kg/day or 
placebo
Subjects
6mg/kg/day or 
placebo
6mg/kg/day or 
placebo
<30kg
4mg/kg/day or 
placebo
4mg/kg/day or 
placebo
2mg/kg/day or 
placebo
2mg/kg/day 
or placebo
During Titration Period dosage may beadjusted up or down 
based on Investigator’s clinical judgment
Dose reached at the end of Titration Period 
will be taken throughout Maintenance Period
Taper based on the maximum dose 
achieved during the Maintenance 
Period
Weeks
Week
Week
Week
Week
Week
Week
Week 7 through
Week
Week
Week
Week
-8 to 0
1
 
2
3
4
5
 
6
Week 16
17 
18 
19 
20
V1
  T1
V2
V3-V4 and T2-T4
V5
V6 –V7 and T5-T6
V8
Taper Visit
Baseline Period
Titration Period
Maintenance Period 
Taper Perioda
(or Transition Period)
b
8mg/kg/day or
placebo
Subjects
6mg/kg/dayor 
placebo
6mg/kg/dayor 
placebo
≥30kg and 
<50kg
4mg/kg/dayor 
placebo
4mg/kg/dayor 
placebo
2mg/kg/dayor 
placebo
2mg/kg/dayor 
placebo
During Titration Period dosage may be adjusted up or down 
based on Investigator’s clinical judgment
Dose reached at the end of Titration Period 
will be taken throughout Maintenance Period. 
Taper based on the maximum dose 
achieved during the Maintenance 
Period
Weeks
Week
Week
Week
Week
Week
Week
Week 7 through
Week
Week
Week
Week
-8 to 0
1
 
2
3
4
5
6
Week 16
17 
18 
19 
20
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
adjusted up or down 
REDACTED COPY 
adjusted up or down 
based on Investigator’s clinical judgment
REDACTED COPY 
based on Investigator’s clinical judgment
We
REDACTED COPY 
Week
REDACTED COPY 
ek
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
1
 
2
3
4
5
 
6
REDACTED COPY 
1
 
2
3
4
5
 
6
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
V8
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
V8
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
adjusted up or down 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
adjusted up or down 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ek
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ek
We
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
We
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
1
 
2
3
4
5
 
6
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
1
 
2
3
4
5
 
6
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
T4
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
T4
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Titration Period
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Titration Period
8mg/kg/day or
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
8mg/kg/day or
placebo
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
placebo
6mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
6mg/kg/dayor 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
or 
placebo
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
placebo
4mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
4mg/kg/dayor 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
or 
placebo
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
placebo
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
placebo
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
placebo
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
During Titration Period dosage may be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
During Titration Period dosage may be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
8 to 0
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
8 to 0
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 29of 97
Figure 5-1: SP0969 overall schematic diagram
V1
    T1
V2
V3-V4 and T2-T4
V5
V6–V7 and T5-T6
V8
Taper Visit
Baseline Period
Titration Period
Maintenance Period 
Taper Perioda
(or Transition Period)
b
400mg/dayor 
placebo
Subjects
300mg/dayor 
placebo
300mg/dayor 
placebo
≥50kg
200mg/dayor
placebo
200mg/dayor 
placebo
100mg/dayor 
placebo
100mg/dayor 
placebo
During Titration Period dosage may be adjusted up or down 
based on Investigator’s clinical judgment
Dose reached at the end of Titration Period will 
be taken throughout Maintenance Period. 
Taper based on the maximum dose 
achieved during the Maintenance 
Period
Weeks
Week
Week
Week
Week
Week
Week
Week 7 through
Week
Week
Week
Week
-8 to 0
1
 
2
3
4
5
6
Week 16
17 
18 
19 
20
T=Telephone Contact; V=Visit
Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo is shown as “placebo.”
Note: The subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout the study.
aThe study week numbers provided are for subjects who complete the Maintenance Period and enter the Taper Period. The study week numbers provided do not apply to subjects 
who enter the Taper Period at other times. The highest possible dose for each week of taperfor each body weight categoryis shown; complete dosing information for the Taper 
Period is provided inTable7‒5. Taper of LCM may not be required for some subjects who discontinue study medication prematurely depending on the treatment option selected 
by the investigator in consultation with the subject and/or parent/legal representative. There will be a 30-day Safety Follow-Up Period (see Table5-3) for subjects not entering 
EP0034.
bSubjects who complete the Maintenance Period and plan to participate in the open-label extension study (EP0034) will participate in a 4-week blinded TransitionPeriod with 
dosing as shown in Figure5‒2. 
REDACTED COPY 
During Titration Period dosage may be adjusted up or down 
REDACTED COPY 
During Titration Period dosage may be adjusted up or down 
Dose reached at the end of Titration Period will 
REDACTED COPY 
Dose reached at the end of Titration Period will 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
We
REDACTED COPY 
Week
REDACTED COPY 
ek
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
1
 
2
3
4
5
6
REDACTED COPY 
1
 
2
3
4
5
6
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo 
REDACTED COPY 
Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo 
REDACTED COPY 
2) will be used to determine dose throughout the study.
REDACTED COPY 
2) will be used to determine dose throughout the study.
for subjects who complete the Maintenance Period and enter the Taper Period. The study w
REDACTED COPY 
for subjects who complete the Maintenance Period and enter the Taper Period. The study w
The highest possible dose for each w
REDACTED COPY 
The highest possible dose for each w
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
V8
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
V8
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Dose reached at the end of Titration Period will 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Dose reached at the end of Titration Period will 
be taken throughout 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
be taken throughout 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
1
 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
1
 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2) will be used to determine dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2) will be used to determine dose throughout the study.
for subjects who complete the Maintenance Period and enter the Taper Period. The study w
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
for subjects who complete the Maintenance Period and enter the Taper Period. The study w
The highest possible dose for each w
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The highest possible dose for each week of taper
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eek of taper
Taper of LCM may not be required for some subjects who 
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Taper of LCM may not be required for some subjects who 
y the investigator in consultation with the subject and/or parent/legal representative. There w
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y the investigator in consultation with the subject and/or parent/legal representative. There w
Subjects who complete the Maintenance Period and plan to participate in the open
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Subjects who complete the Maintenance Period and plan to participate in the open
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 30of 97
Figure 5‒2: SP0969 schematic diagram (Transition Period)
Maintenance Period 
Transition Period
(TV1-TV4)
Entry in to EP0034
12mg/kg/day
12mg/kg/day
11mg/kg/day
11mg/kg/day
Subjects
10mg/kg/day 
10mg/kg/day
10mg/kg/day
<30kg
9mg/kg/day
9mg/kg/day
8mg/kg/day
8mg/kg/day
6mg/kg/day
4mg/kg/day
2mg/kg/day
Placebo
Weeks 7 through16
Week17
Week18
Week19
Week 20
Maintenance Period 
Transition Period
(TV1-TV4)
Entry into EP0034
8mg/kg/day 
8mg/kg/day
7mg/kg/day
7mg/kg/day
Subjects
6mg/kg/day
6mg/kg/day
6mg/kg/day
≥30kg and <50kg
4mg/kg/day
2mg/kg/day
Placebo
Weeks 7 through16
Week17
Week18
Week19
Week 20
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We
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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6mg/kg/day
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6mg/kg/day
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ek
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ek18
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18
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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2mg/kg/day
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2mg/kg/day
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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16
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16
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
05Mar2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 31of 97
Figure 5-2:
SP0969 schematic diagram (Transition Period)
Maintenance Period 
Transition Period
(TV1-TV4)
Entry into EP0034
400mg/day 
400mg/day 
350mg/day
350mg/day
Subjects
300mg/day
300mg/day
300mg/day
≥50kg
200mg/day 
100mg/day 
Placebo
Weeks 7 through16
Week17
Week18
Week19
Week 20
TV=Transition Visit
Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo is shown as “placebo.”
Note: The subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout the study.
REDACTED COPY 
We
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Week
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ek18
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18
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Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo is shown as “place
REDACTED COPY 
Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo is shown as “place
dose throughout the study.
REDACTED COPY 
dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo is shown as “place
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Note: LCM dosing is designated as “mg/kg/day” (oral solution) and “mg/day” (tablets), and matching placebo is shown as “place
dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 32of 97
5.4
Rationale for study design and selection of dose
Epilepsy is a condition for which an improved benefit/risk ratio for medicinal products 
remains a challenge; this is especially true for pediatric patients. Based on the demonstrated 
efficacy and safety of LCM as adjunctive treatment in subjects with epilepsy ≥16years of age
with partial-onset seizures, and the experience with other AEDs in pediatric subjects, it is 
likely that LCM will be an efficacious and safe treatment in the pediatric population with 
partial-onset seizures.
SP0969 is a Phase 3 multicenter, double-blind, randomized, placebo-controlled, 
parallel-group study to investigate the efficacy and safety of LCM as adjunctive therapy in 
subjectswith epilepsy ≥4years to <17years of age with partial-onset seizures.A Phase 3 
study (SP0967) investigating the use of LCM in subjects with epilepsy ≥1 month to <4 years 
of age with partial-onset seizures is planned. 
Based on the currently available LCM pediatric safety and PK data from SP847 and SP1047, 
as well as on information available in the medical literature, the dosing recommendations for 
SP0969 are as follows to achieve LCM plasma concentrations corresponding to the average 
steady-state LCM plasma concentration (C
ss) reached after a LCM400mg/day dose 
administration in adult studies, which is approximately 8μg/mL:
A weight-based dosing scheme is recommended for the Maintenance Period:
Subjects <30kg: LCM8mg/kg/day to 12mg/kg/day
Subjects ≥30kgto <50kg: LCM6mg/kg/day to 8mg/kg/day 
Subjects ≥50kg: LCM 300mg/day to 400mg/day
The LCM (or matching placebo) dose should otherwise remain fixed over the 
Maintenance Period.
To provide dosing flexibility and optimize tolerability for each subject during titration, 
flexible study medication dosing to achieve a minimum target dose for entry into the 
Maintenance Period. The dosing flexibility during the Titration Period includes 4 key 
elements: 
A Titration Period of 6 weeks to allow sufficient time to achieve the minimum target 
dose for entry into the Maintenance Period for subjects who require study medication 
dosing flexibility based on tolerability.
Allowing investigators to holda subject’s study medication dose constant at any time 
during the Titration Period and allowing for multiple holds if needed.
Allowing investigators to back titrate asubject’s study medication dose by full-step or 
half-step increments, with asymmetric dosing as needed for tablets.
Allowing flexibility in the duration a subject must remain on a back-titrated study 
medication dose before a subsequent increase.
REDACTED COPY 
proximately
REDACTED COPY 
proximately 8μg/mL
REDACTED COPY 
 8μg/mL
proximately 8μg/mL
proximately
REDACTED COPY 
proximately 8μg/mL
proximately
ed dosing scheme is recommended
REDACTED COPY 
ed dosing scheme is recommendedfor the Maintenance Period
REDACTED COPY 
for the Maintenance Period
 to 
REDACTED COPY 
 to 12mg/kg/day
REDACTED COPY 
12mg/kg/day
REDACTED COPY 
6mg/kg/day
REDACTED COPY 
6mg/kg/day
CM 300mg/day
REDACTED COPY 
CM 300mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y of LCM as adjunctive therap
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y of LCM as adjunctive therapy in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y in 
A Phase
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A Phase
month to <4 y
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
month to <4 y
 and PK data from SP847 and SP1047, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 and PK data from SP847 and SP1047, 
as well as on information available in the medical literature, the dosing recommendations for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
as well as on information available in the medical literature, the dosing recommendations for 
corresponding 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
corresponding 
) reached after a LCM
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
) reached after a LCM400mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
400mg/day
 8μg/mL
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 8μg/mL:
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:
for the Maintenance Period
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
for the Maintenance Period
12mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
12mg/kg/day
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6mg/kg/day
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6mg/kg/day
CM 300mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CM 300mg/day to 400mg/day
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 to 400mg/day
CM 300mg/day to 400mg/day
CM 300mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CM 300mg/day to 400mg/day
CM 300mg/day
dose should otherwise remain fixed over the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
dose should otherwise remain fixed over the 
To provide dosing flexibility
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
To provide dosing flexibility and optimize tolerability
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 and optimize tolerability
To provide dosing flexibility and optimize tolerability
To provide dosing flexibility
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
To provide dosing flexibility and optimize tolerability
To provide dosing flexibility
 medication 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 medication dosing to achieve a minimum target dose for entry
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
dosing to achieve a minimum target dose for entry
Maintenance Period. The dosing flexibility during the Titration Period includes 4 key
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Maintenance Period. The dosing flexibility during the Titration Period includes 4 key
A Titration Period of 6 weeks to allow sufficient time to achieve the minimum target 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
A Titration Period of 6 weeks to allow sufficient time to achieve the minimum target 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
dose for entry
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dose for entry
dosing 
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dosing flexibility
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flexibility
Allowing investigators to hold
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Allowing investigators to hold
during 
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during 

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


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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
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Page 33of 97
Administration of oral solution by feeding tube is permitted for subjects who are unable 
to swallow the oral solution; however, they are not permitted to exceed the maximum 
dose of LCM400mg/day.
Dosing with oral solution is permitted for subjects weighing ≥50kg who are unable or 
unwilling to swallow tablets.
6 
SELECTION AND WITHDRAWAL OF SUBJECTS
6.1
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committe e (IEC) approved 
written Informed Consent form is signed and dated 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/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 ≥4years to <17years of age.
4. Subject has a diagnosis of epilepsy with partial-onset seizures. The results of ≥1prior 
electroencephalogram (EEG) AND 1prior magnetic resonance imaging/computerized 
tomography scan should be consistent with the above diagnosis.
5. Subject has been observed to have uncontrolled partial-onset seizures after an adequate 
course of treatment (in the opinion of the investigator) with ≥2AEDs (concurrently or 
sequentially).
6. Subject must have been observed to have on average ≥2 partial-onset seizures per 28days
with seizure-free phase no longer than 21days in the 8-week period prior to entry into the 
Baseline Period. During this study, subjects must have reported ≥2 partial-onset seizures 
during the 8-week prospective Baseline Period to be eligible for randomization at Visit 2. 
(Note: In the case of simple partial-onset seizures, only those seizures with motor signs 
will be counted towards meeting the inclusion criterion.)
7. Subject is on a stable dosage regimen of 1 to≤3 AEDs. The daily dosage regimen of 
concomitant AED therapy must be kept constant for a period of ≥4weeksprior to the 
Baseline Period.
8. Vagal nerve stimulation is allowed and will not be counted as a  concomitant AED. 
The 
VNS devicemust be implanted for ≥6 months before Visit 1, and the devicesettings must 
be stable for ≥4 weeks before Visit 1and be kept stable during the Baseline Period.Use 
of the VNS device magnet is allowed.
REDACTED COPY 
ye
REDACTED COPY 
years of age.
REDACTED COPY 
ars of age.
y with partial
REDACTED COPY 
y with partial-
REDACTED COPY 
-onset seizures. The results of 
REDACTED COPY 
onset seizures. The results of 
prior magnetic resonance imaging/computerized 
REDACTED COPY 
prior magnetic resonance imaging/computerized 
can should be consistent with the 
REDACTED COPY 
can should be consistent with the 
Subject has been observed to have uncontrolled partial
REDACTED COPY 
Subject has been observed to have uncontrolled partial
course of treatment (in the opinion of the investigator) with 
REDACTED COPY 
course of treatment (in the opinion of the investigator) with 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(IEC) approved 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(IEC) approved 
 the parent(s) or legal 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 the parent(s) or legal 
Informed Consent form or a specific Assent form, where required, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Informed Consent form or a specific Assent form, where required, 
2. Subject/legal representative is considered reliable and capable of adhering to the protocol 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(eg, able to understand and complete diaries), visit schedule, and medication intake 
ars of age.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ars of age.
onset seizures. The results of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizures. The results of 
prior magnetic resonance imaging/computerized 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
prior magnetic resonance imaging/computerized 
can should be consistent with the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
can should be consistent with the above diagnosis
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
above diagnosis
Subject has been observed to have uncontrolled partial
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject has been observed to have uncontrolled partial
course of treatment (in the opinion of the investigator) with 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
course of treatment (in the opinion of the investigator) with 
Subject must have been observed to have on average 
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Subject must have been observed to have on average 
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free phase no longer than 21
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
free phase no longer than 21
Baseline Period. During this study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Baseline Period. During this study
week prospective Baseline Period to be
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
week prospective Baseline Period to be
(Note: In the case of simple partial
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(Note: In the case of simple partial
will be counted towards meeting the inclusion criterion.)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be counted towards meeting the inclusion criterion.)
Subject is on a stable dosage regimen of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject is on a stable dosage regimen of 
concomitant AED therapy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
concomitant AED therapy
Baseline Period.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Baseline Period.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
8. Vagal nerve stimulation is allowed and will not be counted as a  concomitant AED. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
8. Vagal nerve stimulation is allowed and will not be counted as a  concomitant AED. 
VNS device
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
VNS device
be stable 
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be stable 


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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
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Page 34of 97
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Subject has previously participated in this studyor subject has been assigned to LCM in a 
previous LCM study.
2. Subject has participated in another study of an investigational medicinal product (IMP) or 
a medical device within ≤2 months of Visit 1 or is currently participating in another study 
of an IMP or a medical device.
3. Subject has any medical or psychiatric condition that, in the opinion of the investigator, 
could jeopardize or would compromise the subject’s ability to participate inthis study.
4. Subject≥6years of agehas 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 a positive response (“Yes”) to either Question 4 or Question5 of 
the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening.
5. Subject has a known hypersensitivity to any component of the IMP or has ever received 
LCM.
6. Female subject who is pregnant or nursing, and/or a female subj ect of childb
earing 
potential who is not surgically sterile or does not practice 1highly effective method of 
contraception (according toInternational Conference on Harmonisation [ICH]guidance 
defined as those that result in a failure rate of less than 1% per year when used 
consistently and correctly), unless sexually abstinent, for the duration of the study. 
Female subject of childbearing potential taking enzyme-inducing antiepileptic drugs 
(EI-AEDs: carbamazepine, phenytoin, barbiturates, primidone, topiramate, 
oxcarbazepine) who is not surgically sterile or does not practice 1highly effective method 
of contraception according to the WHO recommendation (ie, depot medroxyprogesterone 
acetate, norethisterone enantate, intrauterine devices, combined injectables, and 
progestogen implants) with administration of EI-AEDs OR does not practice 2 combined 
methods of contraception (ie, combined hormonal contraception plus barrier method with 
spermicidal agent), unless sexually abstinent, for the duration of the study.
7. Subject  has a medical condition that could be expected in the opini on of the investigator 
to interfere with drug absorption, distribution, metabolism, or excretion.
8. Subject has experienced febrile seizures exclusively. The occurrence of febrile seizures in 
addition to other unprovoked seizures is not exclusionary.
9. Subject is on a ketogenic or other specialized diet. If the subject was on a specialized diet 
in the past, they must be off the diet for ≥2 months prior to the Baseline Period.
10. Subject has an alanine aminotransferase (ALT), aspartate aminot ransferase (AST), or 
total bilirubin level ≥2times the upper limit of normal (ULN), or creatinine clearance less 
than 30mL/min.
11. Subject has a clinically relevant ECG abnormality, in the opinion of the investigator (eg, 
second or third degree heart block at rest or a corrected QT interval [QTc] greater than 
450ms).
REDACTED COPY 
6. Female subject who is pregnant or nursing, and/or a female subj ect of childb
REDACTED COPY 
6. Female subject who is pregnant or nursing, and/or a female subj ect of childb
 sterile or does not practice 1
REDACTED COPY 
 sterile or does not practice 1
ternational Conference on Harmonisation [
REDACTED COPY 
ternational Conference on Harmonisation [
defined as those that result in a failure rate of less than 1% per 
REDACTED COPY 
defined as those that result in a failure rate of less than 1% per 
), unless sexually
REDACTED COPY 
), unless sexually
Female subject of childbearing potential taking enzy
REDACTED COPY 
Female subject of childbearing potential taking enzy
-AEDs: carbamazepine, phen
REDACTED COPY 
-AEDs: carbamazepine, phenyt
REDACTED COPY 
ytoin, barbiturates, primidone, topiramate, 
REDACTED COPY 
oin, barbiturates, primidone, topiramate, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y participating in another stud
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y participating in another study 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y 
y medical or psychiatric condition that, in the opinion of the investigator, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y medical or psychiatric condition that, in the opinion of the investigator, 
this study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
this study
 of suicide attempt (including an act
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of suicide attempt (including an act
suicidal ideation in the past 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
suicidal ideation in the past 
 a positive response (“Yes”) to either Quest
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 a positive response (“Yes”) to either Question
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ion4 or Question
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
4 or Question
SSRS) at Screening.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
SSRS) at Screening.
y component of the IMP or has ever received 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y component of the IMP or has ever received 
6. Female subject who is pregnant or nursing, and/or a female subj ect of childb
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
6. Female subject who is pregnant or nursing, and/or a female subj ect of childb
 sterile or does not practice 1
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 sterile or does not practice 1
ternational Conference on Harmonisation [
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ternational Conference on Harmonisation [
defined as those that result in a failure rate of less than 1% per 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
defined as those that result in a failure rate of less than 1% per 
), unless sexually
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
), unless sexually abstinent, for the duration of the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 abstinent, for the duration of the study
), unless sexually abstinent, for the duration of the study
), unless sexually
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
), unless sexually abstinent, for the duration of the study
), unless sexually
Female subject of childbearing potential taking enzy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Female subject of childbearing potential taking enzy
oin, barbiturates, primidone, topiramate, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
oin, barbiturates, primidone, topiramate, 
rbazepine) who is not surgically sterile or does not practice 1
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rbazepine) who is not surgically sterile or does not practice 1
ng to the WHO recommendation (ie,
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ng to the WHO recommendation (ie,
, norethisterone enantate
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, norethisterone enantate, intrauterine devices, combined injectables, and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, intrauterine devices, combined injectables, and 
ants) with administration of EI
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ants) with administration of EI
methods of contraception (ie,
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
methods of contraception (ie,
spermicidal agent), unless sexually abstinent, for the duration of the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
spermicidal agent), unless sexually abstinent, for the duration of the study
has a medical condition that could be expected in the opinion of the investigator 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
has a medical condition that could be expected in the opinion of the investigator 
to interfere with drug absorption, distribution, metabolism, or excretion.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
to interfere with drug absorption, distribution, metabolism, or excretion.
Subject has 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject has experienced febrile seizures exclusively
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
experienced febrile seizures exclusively
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
additio
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
addition to other unprovoked seizures is not exclusionary.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
n to other unprovoked seizures is not exclusionary.
Subject is on a ketogenic or other 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject is on a ketogenic or other 
in the past, they
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
in the past, they
10. Subject has an alanine aminotransferase (ALT), aspartate aminot ransferase (AST), or 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
10. Subject has an alanine aminotransferase (ALT), aspartate aminot ransferase (AST), or 


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 35of 97
12. Subject has hemodynamically significant congenital heart disease.
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 nonepileptic events that could be confused with sei zures.
16. Subject has a current diagnosis of Lennox-Gastaut syndrome, primary generalized 
epilepsy, mixed seizure disorder (partial and primarily generalized seizures),or purely 
nocturnal seizures.
17. Subject has a history of convulsive status epilepticus ≤2 months prior to the Baseline 
Period.
18. Subject has been treated with vigabatrin and experienced any vision loss. Subjects who 
have received vigabatrin in the past must have documentation of an assessment for vision 
loss prior to study entry or documentation of why visual field testing cannot be 
performed.
19. Subject has been treated with felbamate and has experienced any serious toxicity issues 
(defined as liver failure, aplastic anemia) with this treatment. Subjects treated with 
felbamate for <12months are excluded. Note: any subject who has been treated with 
felbamate for ≥12 months and has not experienced serious toxicity issues is eligible.
21. Subject has a medically documented history of alcohol or drug abuse.
22. Subject has a known cardiac sodium channelopathy, such as Brugada syndrome.
23. Subject has an acute or sub-acutely progressive central nervous system disease. Subject 
has epilepsy secondary to a progressing cerebral disease or any other progressively 
neurodegenerative disease (malignant brain tumor or Rasmussen Syndrome).
6.3
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care.
Subjects mustbe withdrawn from this study if any of the following events occur:
1. Subject experiences intolerable AEs, including clinically relevant abnormal laboratory 
findings that, in the opinion of the investigator, preclude further participation in the study.
2. The sponsor or a regulatory agency requests withdrawal of the subject.
3. Subject has QTc interval ≥500ms that is confirmed by a cardiologist overread on any
ECG.
4. Subject develops a second degree atrioventricular (AV) block while awake or develops a 
third degree AV block.
5. For subjects ≥6years of age, subject has actualsuicidal ideation since last visit as 
indicated by a positive response (“Yes”) to either Question 4 or Question5 of the 
C-SSRS. The subject should be referred immediately to a Mental Healthcare Professional 
and must be withdrawn from the study.
REDACTED COPY 
months are excluded. Note: any subject who has been treated with 
REDACTED COPY 
months are excluded. Note: any subject who has been treated with 
≥12 months and has not experienced se
REDACTED COPY 
≥12 months and has not experienced se
y documented history
REDACTED COPY 
y documented history of alcohol or drug abuse.
REDACTED COPY 
 of alcohol or drug abuse.
y documented history of alcohol or drug abuse.
y documented history
REDACTED COPY 
y documented history of alcohol or drug abuse.
y documented history
sodium channelopathy
REDACTED COPY 
sodium channelopathy
acutel
REDACTED COPY 
acutely progressive central nervous 
REDACTED COPY 
y progressive central nervous 
y secondary to a progressing cerebral disease or an
REDACTED COPY 
y secondary to a progressing cerebral disease or an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
months prior to the Baseline 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
months prior to the Baseline 
n loss. Subjects who 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
n loss. Subjects who 
have received vigabatrin in the past must have documentation of an assessment for vision 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
have received vigabatrin in the past must have documentation of an assessment for vision 
y visual field testing cannot be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y visual field testing cannot be 
ienced an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ienced any serious toxicity
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y serious toxicity
(defined as liver failure, aplastic anemia) with this treatment. Subjects treated with 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(defined as liver failure, aplastic anemia) with this treatment. Subjects treated with 
months are excluded. Note: any subject who has been treated with 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
months are excluded. Note: any subject who has been treated with 
≥12 months and has not experienced se
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
≥12 months and has not experienced serious toxicity
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rious toxicity
 of alcohol or drug abuse.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of alcohol or drug abuse.
sodium channelopathy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sodium channelopathy
y progressive central nervous 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y progressive central nervous 
y secondary to a progressing cerebral disease or an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y secondary to a progressing cerebral disease or an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
neurodegenerative disease (malignant brain tumor or Rasmussen Sy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
neurodegenerative disease (malignant brain tumor or Rasmussen Sy
Withdrawal criteria
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Withdrawal criteria
Subjects are free to withdraw from the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subjects are free to withdraw from the study
be withdrawn from 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
be withdrawn from 
1. Subject experiences intolerable AEs, including clinically
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
1. Subject experiences intolerable AEs, including clinically
findings that, in the opinion of the inves
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
findings that, in the opinion of the inves
The sponsor or a regulatory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The sponsor or a regulatory
Subject has QTc interval 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject has QTc interval 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ECG.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ECG.
4.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
4. Subject develops a second degree atriovent
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject develops a second degree atriovent


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 36of 97
6. Subject is unwilling or unable to continue, or the parent/legal representative is unwilling 
or unable to allow the subject to continue in the study.
7. Investigator decides that withdrawal from further participati on would be in the subject’s 
best interest.
8. Subject experiences convulsive status epilepticus.
9. Subject uses rescue medication in excess of that permitted by the protocol.
10. In the case of liver function test (LFT) results of transaminas es (AST, ALT, or both) 
≥3xULN 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 
>1week later.
11. Female subject whoachieves menarche and does not practice contraception as provided
in Exclusion Criteria 6 unless sexually abstinent. Subject becomes pregnant, as evidenced 
by a positive pregnancy test. 
12.Subject needs any alteration in AED daily dose or VNS settings.
Participation in this study maybe discontinued for any of the following reasons:
1. 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 the 
study).
2. Subject requires a medication that is not permitted by the protocol.
3. Subject and/or delegated caregiver is noncompliant with study procedures or medication, 
in the opinion of the investigator.
4. Subject needs any alteration in AEDdosing frequency.
5. 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.
Investigators should attempt to obtain information on subjects, in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow-up, the investigator should make 
every effort (≥1 phone call and 1written message to the parent[s] or legal representative), and 
document his/her effort (date and summary of the phone call and copy of the written message 
in the source documents) to complete the final evaluation. All results of these evaluations and 
observations, together with a narrative description of the reason(s) for removing the subject, 
must be recorded in the source documents. The Case Report form (CRF) must document the 
primary reason for withdrawal or discontinuation.
Investigators should contact the Medical Monitor whenever possible to discuss the 
withdrawal of a subject in advance.
REDACTED COPY 
be discontinued for any
REDACTED COPY 
be discontinued for any of the following reasons:
REDACTED COPY 
 of the following reasons:
be discontinued for any of the following reasons:
be discontinued for any
REDACTED COPY 
be discontinued for any of the following reasons:
be discontinued for any
y clinically relevant change in medical or ps
REDACTED COPY 
y clinically relevant change in medical or ps
condition warrants discontinuation from the 
REDACTED COPY 
condition warrants discontinuation from the 
Subject requires a medication that is not permitted by
REDACTED COPY 
Subject requires a medication that is not permitted by
bject and/or delegated caregiver is noncompliant with study
REDACTED COPY 
bject and/or delegated caregiver is noncompliant with study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
10. In the case of liver function test (LFT) results of transaminas es (AST, ALT, or both) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
10. In the case of liver function test (LFT) results of transaminas es (AST, ALT, or both) 
T, or both) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
T, or both) 
 discontinued and the subject 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 discontinued and the subject 
. The LFTs will be repeated as soon as possible, and in no case 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. The LFTs will be repeated as soon as possible, and in no case 
and does not practice contraception as 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
and does not practice contraception as 
. Subject becomes pregnant
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. Subject becomes pregnant
 dose or VNS settings.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 dose or VNS settings.
 of the following reasons:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of the following reasons:
y clinically relevant change in medical or ps
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y clinically relevant change in medical or ps
condition warrants discontinuation from the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
condition warrants discontinuation from the 
Subject requires a medication that is not permitted by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject requires a medication that is not permitted by
bject and/or delegated caregiver is noncompliant with study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
bject and/or delegated caregiver is noncompliant with study
in the opinion of the investigator.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
in the opinion of the investigator.
y alteration in AED
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y alteration in AED
5. Transaminases (AST, ALT, or both) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
5. Transaminases (AST, ALT, or both) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
total bilirubin, will be repeated within a few days. If the repeat testing confirms the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
total bilirubin, will be repeated within a few days. If the repeat testing confirms the 
 (ie, transaminases are 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 (ie, transaminases are 
y monitoring of LFTs should continue until resolved (ie, <3x
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y monitoring of LFTs should continue until resolved (ie, <3x
tion). The investigator is to decide whether or not to stop the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
tion). The investigator is to decide whether or not to stop the study
Investigators should attempt to obtain information on subjects, in the case of withdrawal or 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Investigators should attempt to obtain information on subjects, in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
discontinuation. For subjects considered as lost to follow-
 effort (
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 effort (
document his/her effort (date and summary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
document his/her effort (date and summary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
in the source documents) to complete the final evaluatio
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
in the source documents) to complete the final evaluatio
observations, together with a narrative description of the reason(s) for removing the subject, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
observations, together with a narrative description of the reason(s) for removing the subject, 
must be recorded in the source documents. The C
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
must be recorded in the source documents. The C


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 37of 97
7
STUDY TREATMENTS
7.1
Description of investigational medicinal products
The IMPwill be provided as LCM oral solution (syrup) (LCM10mg/mL), LCM tablets 
(LCM50mg and LCM 100mg), and matching placebos.
The LCM10mg/mL oral solution and matching placebo oral solution are colorless to pale 
yellow in appearance. Both oral solutions will be packaged in amber polyethylene 
terephthalate(PET) bottles. Oral solution doses will be measured and administered via a 
dosing syringe.
The LCM50mg tablets and matching placebo are pinkish, oval tablets debossed with “SP” on 
one side and “50” on the other side. The LCM 100mg tablets and matching placebo are dark 
yellow, oval tablets debossed with “SP” on one side and “100” on the other side. Tablets will 
be packaged in high density polyethylene (HDPE) bottles.
7.2
Treatmentsto be administered
Study medication will be administered orally bid (at approximately 12-hour intervals in the 
morning and in the evening).
At Visit 2, subjects will be randomized to receive either LCM (oral solution for subjects 
weighing <50kgor tabletsfor subjects weighing ≥50kg),or matching placebo. Oral solution 
will be allowed for subjects weighing ≥50kg who are unwilling or unable to swallow tablets; 
however, they are not permitted to exceed the maximum dose of LCM400mg/day. 
Administration of oral solution by feeding tube is permitted for subjects who are unable to 
swallow the oral solution. 
At the end of Visit 2, subjects should take the first dose of study medication while in the 
clinic. At each subsequent clinic visit, subjects should take study medication (and any 
concomitant AEDs) at the regular time(s). The subject’s body weight at Baseline (Visit 2) 
will be used to determine dose throughout the study.
SP0969 will target Maintenance Period doses of LCM 8mg/kg/day to 12mg/kg/day for 
subjects weighing <30kg, LCM 6mg/kg/day to 8mg/kg/day for subjects weighing ≥30kg to 
<50kg, and LCM 300mg/day to 400mg/day for subjects weighing ≥50kg, or matching
placebo.
7.2.1
Titration Period
Table 7‒1provides the recommended LCM (or matching placebo) dosing during the Titration 
Period for subjects to reach the target doses for the Maintenance Period. All subjects are 
required to complete Week 1 study medication dosing before dosing flexibility is allowed 
based on tolerability.
REDACTED COPY 
, subjects will be randomized to receive either L
REDACTED COPY 
, subjects will be randomized to receive either L
≥50kg
REDACTED COPY 
≥50kg
≥50kg who are unwilling or unable to swallow tablets
REDACTED COPY 
≥50kg who are unwilling or unable to swallow tablets
however, they are not permitted to exceed the maximum dose of L
REDACTED COPY 
however, they are not permitted to exceed the maximum dose of L
 feeding tube is permitted for subjects who are unable to 
REDACTED COPY 
 feeding tube is permitted for subjects who are unable to 
, subjects should take the first dose of study
REDACTED COPY 
, subjects should take the first dose of study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(PET) bottles. Oral solution doses will be measured and administered via a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(PET) bottles. Oral solution doses will be measured and administered via a 
50mg tablets and matching placebo are pinkish, oval tablets debossed with “SP” on 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
50mg tablets and matching placebo are pinkish, oval tablets debossed with “SP” on 
acebo are dark 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
acebo are dark 
llow, oval tablets debossed with “SP” on one side and “100” on the other side. Tablets will 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
llow, oval tablets debossed with “SP” on one side and “100” on the other side. Tablets will 
mately
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
mately 12
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 12
mately 12
mately
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
mately 12
mately
, subjects will be randomized to receive either L
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, subjects will be randomized to receive either LCM (oral solution 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CM (oral solution 
≥50kg
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
≥50kg),
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
),or matching placebo. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
or matching placebo. 
≥50kg who are unwilling or unable to swallow tablets
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
≥50kg who are unwilling or unable to swallow tablets
however, they are not permitted to exceed the maximum dose of L
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
however, they are not permitted to exceed the maximum dose of L
 feeding tube is permitted for subjects who are unable to 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 feeding tube is permitted for subjects who are unable to 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, subjects should take the first dose of study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, subjects should take the first dose of study
At each subsequent clinic visit, subjects should take study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
At each subsequent clinic visit, subjects should take study
concomitant AEDs) at the regular time(s).
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
concomitant AEDs) at the regular time(s).
will be used to determine dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be used to determine dose throughout the study.
SP0969 will target Maintenance Period doses of LCM 8mg/kg/day to 1
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
SP0969 will target Maintenance Period doses of LCM 8mg/kg/day to 1
subjects weighing <30kg, L
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
subjects weighing <30kg, LCM 6mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CM 6mg/kg/day
50kg, and LCM 300mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
50kg, and LCM 300mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Titration Period
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Titration Period
1
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1provides 
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provides 
Period for subjects to reach 
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Period for subjects to reach 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
required to complete 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
required to complete 
based on tolerabilit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
based on tolerabilit


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 38of 97
Table7‒1: Recommended dosing schedule for LCM (or matching placebo)
during the Titration Period
Body weight 
category
(formulation)
Target LCM (or matching placebo) doses for the Titration Period
Week 1a
Week 2 
Week 3 
Week 4 
Week 5 
Week 6
<30kg(oral 
solution)
2mg/kg/day 4mg/kg/day 6mg/kg/day 
8mg/kg/day
10mg/kg/day
12mg/kg/day
≥30kg to 
<50kg(oral 
solution)
2mg/kg/day 4mg/kg/day 6mg/kg/day 
8mg/kg/day 
8mg/kg/day 
8mg/kg/day
≥50kg(tablets)
100mg/day 200mg/day 
300mg/day 
400mg/day 
400mg/day 
400mg/day
LCM=lacosamide
Note: Subjects may not receivedoses higher than LCM 12mg/kg/day (body weight <30kg), LCM8mg/kg/day 
(body weight ≥30kg to <50kg), or LCM 400mg/day (body weight ≥50kg), or matching placebo. 
Note: The subject’s body weight at Baseline(Visit 2)will be used to determine dose throughout the study.
aAll subjects are required to complete Week1 study medication dosing before dosing flexibility is allowed 
based on tolerability. Subjects who are unable to complete the Titration Period or subjects who will not be able 
to attain at least the minimum Maintenance Period target dose,should be withdrawn and enter the Taper 
Period.
After completion of Week 1, investigators will assess whether a subject would tolerate a 
further dose increase or whether a subject should hold the Week 1 dose for a longer duration.
This hold will be at the investigator’s discretion. 
Table 7‒2provides LCM (or matching placebo) dosing with flexibility based on tolerability
during the Titration Period.
REDACTED COPY 
After completion of Week 1, investigators will assess whether a subject would tolerate a 
REDACTED COPY 
After completion of Week 1, investigators will assess whether a subject would tolerate a 
further dose increase or whether a subject should hold the Week 1 dose for a longer duration.
REDACTED COPY 
further dose increase or whether a subject should hold the Week 1 dose for a longer duration.
at the investigator’s discretion. 
REDACTED COPY 
at the investigator’s discretion. 
or matching placebo
REDACTED COPY 
or matching placebo
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2mg/kg/day 4mg/kg/day 6mg/kg/day 
8mg/kg/day 
8mg/kg/day 
8mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2mg/kg/day 4mg/kg/day 6mg/kg/day 
8mg/kg/day 
8mg/kg/day 
8mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
100mg/day 200mg/day 
300mg/day 
400mg/day 
400mg/day 
400mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
100mg/day 200mg/day 
300mg/day 
400mg/day 
400mg/day 
400mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
eight <30kg), LCM
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
eight <30kg), LCM
≥50kg), or matching placebo. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
≥50kg), or matching placebo. 
will be used to determine dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be used to determine dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
dosing before dosing flexibility 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
dosing before dosing flexibility 
unable to complete the Titration Period or subjects who will not be able 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
unable to complete the Titration Period or subjects who will not be able 
should be withdrawn and enter the Taper 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
should be withdrawn and enter the Taper 
After completion of Week 1, investigators will assess whether a subject would tolerate a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
After completion of Week 1, investigators will assess whether a subject would tolerate a 
further dose increase or whether a subject should hold the Week 1 dose for a longer duration.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
further dose increase or whether a subject should hold the Week 1 dose for a longer duration.
at the investigator’s discretion. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
at the investigator’s discretion. 
or matching placebo
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
or matching placebo)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
)dosing with 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
dosing with 


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 39of 97
Table7‒2: Dosing ofLCM (or matching placebo)with flexibility based on 
tolerability during the Titration Period
Body weight category
(formulation)
Target LCM (or 
matching 
placebo) dose 
increase/week
a
(titration)
LCM (or matching 
placebo) dose decrease per
back titration step
Subsequent LCM (or 
matching placebo) dose 
increase
b
(dose increase after back 
titration step)
Min
Max
Min
Max
<30kg (oral solution)
2mg/kg/day 
1mg/kg/day 
2mg/kg/day 
1mg/kg/day 
2mg/kg/day
≥30kg to <50kg (oral 
solution)
≥50kg (tablets)
100mg/day 
50mg/day 
100mg/day 
50mg/day 
100mg/day
LCM=lacosamide; Max=maximum; Min=minimum
Note: Asymmetrical dosing with no more than 50mg difference between morning and evening doses will be 
allowed for subjects taking tablets who require back titration in a 50mg increment (ie, only 50mg and 100mg 
tablets are available).
Note: The subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout the study.
aTitration step to achieve a dose not previously administered
bTitration step subsequent to a back titration
There is no limit to the number of back titration steps or dose holds allowed and all are at the 
investigator’s discretion; however, subjects must achieve the minimum LCM (or matching 
placebo) target dose for their body weight category by the end of the Titration Period. If it 
becomes apparent that a subject will not be able to reach the minimum target dose,then the 
subject should be withdrawnfrom the TitrationPeriod and enter the Taper Period.
Subjects who have their study medication titratedto a higher dose not previously 
administered should remain at that dose for ≥7 days unless a back titrationstep is required 
based on tolerability. Subjects who have their study medication back titrated must remain on 
the lower dose for ≥3days (in order to reach steady state) before a subsequent dose increase.
After back titration, subjects who return to a higher dose previously administered must 
maintain that dose for ≥3 days before subsequent titration to a higher dose.
As outlined in Table 7‒3, subjects will be required to achieve and maintain at least a
minimum LCM (or matching placebo) dose for at least the final 3days of Week6 to be 
eligible for entryinto the Maintenance Period. Subjects may have a back titration step as late 
as the last day of Week6, as long as the minimum target dose is maintained. 
REDACTED COPY 
steps 
REDACTED COPY 
steps or dose holds allowed and all are at the 
REDACTED COPY 
or dose holds allowed and all are at the 
investigator’s discretion; however, subjects must achieve the minimum 
REDACTED COPY 
investigator’s discretion; however, subjects must achieve the minimum 
category
REDACTED COPY 
category
REDACTED COPY 
becomes apparent that a subject will not be able to reach the minimum target dose
REDACTED COPY 
becomes apparent that a subject will not be able to reach the minimum target dose
Titration
REDACTED COPY 
Titration
 medication 
REDACTED COPY 
 medication 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Max
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Max
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2mg/kg/day 
1mg/kg/day 
2mg/kg/day 
1mg/kg/day 
2mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2mg/kg/day 
1mg/kg/day 
2mg/kg/day 
1mg/kg/day 
2mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
50mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
50mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
orning and evening doses will be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
orning and evening doses will be 
ed for subjects taking tablets who require back titration in a 50mg increment (ie, only 50mg and 100mg 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ed for subjects taking tablets who require back titration in a 50mg increment (ie, only 50mg and 100mg 
2) will be used to determine dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2) will be used to determine dose throughout the study.
or dose holds allowed and all are at the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
or dose holds allowed and all are at the 
investigator’s discretion; however, subjects must achieve the minimum 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
investigator’s discretion; however, subjects must achieve the minimum 
category
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categoryby
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
by the end of the Titration Period. If 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 the end of the Titration Period. If 
by the end of the Titration Period. If 
by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
by the end of the Titration Period. If 
by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
becomes apparent that a subject will not be able to reach the minimum target dose
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
becomes apparent that a subject will not be able to reach the minimum target dose
Titration
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
TitrationPeriod and enter the Taper Period.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Period and enter the Taper Period.
 medication 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 medication titrate
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
titrate
should remain at that dose for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
should remain at that dose for 
y. Subjects who 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y. Subjects who have their study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
have their study
s (in order to reach steady
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s (in order to reach steady
After back titration, subjects who return to a higher dose previously
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
After back titration, subjects who return to a higher dose previously
≥3 day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
≥3 days before subsequent titration to a higher dose.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s before subsequent titration to a higher dose.
7
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7‒
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‒3
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3, s
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, s
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CM (or matching placebo) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CM (or matching placebo) 
eligible for entry
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
eligible for entryinto the Maintenance Pe
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
into the Maintenance Pe
as the last day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
as the last day of Week
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of Week
as the last day of Week
as the last day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
as the last day of Week
as the last day


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 40of 97
Table7‒3: Required LCM (or matching placebo) dose for at least the final 
3days of Week 6
Body weight category
(formulation)
LCM (or matching placebo)dose for at least the final 3days of Week 6
Min
Max
<30kg(oral solution)
8mg/kg/day
12mg/kg/day
≥30kg to <50kg(oral solution)
6mg/kg/day
8mg/kg/day
≥50kg(tablets)
300mg/day
400mg/day
LCM=lacosamide; Max=maximum; Min=minimum
Note: The subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout the study.
7.2.2
Maintenance Period
Subjectswho reach and maintain at least the minimumstudy medication dose for at least the 
final 3 days of the Titration Period,will enter a 10-week Maintenance Period at the dose they 
received on the finalday of the Titration Period (Table7‒3).Lacosamide (or matching 
placebo) doses will remain stable throughout the Maintenance Period. Subjects who require a 
change in dose during the Maintenance Period will be withdrawn from the Maintenance 
Period and enter the Taper Period.Taper of LCM may not be required for some subjects who 
discontinuestudy medication prematurely, depending on the treatment option selected by the 
investigator in consultation with the subject and/or parent/legal representative.
7.2.3 
Transition Period (for subjects who plan to enter EP0034)
At the end of the Maintenance Period (Visit 8), all subjects who complete the Maintenance 
Period will be offered the opportunity to enroll in an open-label extension study (EP0034).
Subjects who plan to enroll in EP0034will proceed to a 4-week blinded Transition Period. 
Subjects randomized to LCM will maintain their Maintenance Period dose throughout the 
Transition Period. Subjects randomized to placebo will transition in a double-blind fashion to 
LCM dosing as described Table 7‒4. At the completion of the Transition Period, subjects 
eligible to enter EP0034 will be placed on a common dose (see Figure5‒2)based on body 
weight category at EP0034 entry.
REDACTED COPY 
 not be required for some subjects who 
REDACTED COPY 
 not be required for some subjects who 
y, depending on the treatment option selected b
REDACTED COPY 
y, depending on the treatment option selected b
investigator in consultation with the subject and/or parent/legal representative.
REDACTED COPY 
investigator in consultation with the subject and/or parent/legal representative.
Transition Period (for subjects who 
REDACTED COPY 
Transition Period (for subjects who 
At the end of the Maintenance Period (Visit
REDACTED COPY 
At the end of the Maintenance Period (Visit8
REDACTED COPY 
8), all subjects who complete the Maintenance 
REDACTED COPY 
), all subjects who complete the Maintenance 
 to enroll in an open
REDACTED COPY 
 to enroll in an open
EP0034
REDACTED COPY 
EP0034will proceed to a 
REDACTED COPY 
will proceed to a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2) will be used to determine dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2) will be used to determine dose throughout the study.
dose 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
dose for at least the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
for at least the 
week Maintenance Period at the dose they
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
week Maintenance Period at the dose they
Lacosamide 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Lacosamide (or matching 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(or matching 
doses will remain stable throughout the Maintenance Period. Subjects who require a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
doses will remain stable throughout the Maintenance Period. Subjects who require a 
change in dose during the Maintenance Period will be withdraw
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
change in dose during the Maintenance Period will be withdrawn from the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
n from the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 not be required for some subjects who 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 not be required for some subjects who 
y, depending on the treatment option selected b
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y, depending on the treatment option selected b
investigator in consultation with the subject and/or parent/legal representative.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
investigator in consultation with the subject and/or parent/legal representative.
Transition Period (for subjects who 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Transition Period (for subjects who 
), all subjects who complete the Maintenance 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
), all subjects who complete the Maintenance 
 to enroll in an open
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 to enroll in an open
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will proceed to a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will proceed to a 
Subjects randomized to LCM will maintain their Maintenance Period dose throughout the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subjects randomized to LCM will maintain their Maintenance Period dose throughout the 
Transition Period. Subjects randomized to placebo will transition 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Transition Period. Subjects randomized to placebo will transition 
Table
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Table7
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7‒
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
‒4
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4
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. At the completion of the Transition Period, subjects 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. At the completion of the Transition Period, subjects 
eligible to enter EP0034 will be placed on a common dose 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
eligible to enter EP0034 will be placed on a common dose 
EP0034
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
EP0034entry
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entry


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 41of 97
Table7‒4: Transition Period LCM dosingschedulefor subjects randomized to 
placebo
Body weight category 
(formulation)
LCM doses for the Transition Period 
Week 17 
Week 18 
Week 19 
Week 20
<30kg (oral solution)
2mg/kg/day 
4mg/kg/day 
6mg/kg/day 
8mg/kg/day
≥30kg to <50kg (oral solution) 
2mg/kg/day 
4mg/kg/day 
6mg/kg/day 
6mg/kg/day
≥50kg(tablets)
100mg/day 
200mg/day 
300mg/day 
300mg/day
LCM=lacosamide
Note: The subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout the study.
7.2.4 
Taper Period (for subjects not entering EP0034)
A blinded Taper Period (2to 4 weeks, depending on dose achieved) will be required for 
subjects who discontinue study medication prematurelyand for subjects who complete the 
Maintenance Period but choose not to enter the open-label extension study (EP0034).
Table 7‒5provides the taper steps based on the dose of LCM (or matching placebo) 
achieved. A slow taper is permitted if medically necessary. Whenever possible, these cases 
should be discussed with the medical monitor prior to withdrawing the subject from the 
study, especially in cases in which withdrawalcriteria have been met. In case of an 
emergency, a faster taper is permitted after discussion with the medical monitor, whenever 
possible.Taper of LCM may not be required for some subjects who discontinuestudy 
medication prematurely, depending on the treatment option selected by the investigator in 
consultation with the subject and/or parent/legal representative.
REDACTED COPY 
y necessary
REDACTED COPY 
y necessary
medical monitor prior to withdrawing the subject from the 
REDACTED COPY 
medical monitor prior to withdrawing the subject from the 
criteria have been met. In case of an 
REDACTED COPY 
criteria have been met. In case of an 
, a faster taper is permitted after discussion with the medical monitor, whenever 
REDACTED COPY 
, a faster taper is permitted after discussion with the medical monitor, whenever 
 not be required for some subjects who 
REDACTED COPY 
 not be required for some subjects who 
REDACTED COPY 
, depending on the treatment option selected by the investigator in 
REDACTED COPY 
, depending on the treatment option selected by the investigator in 
consultation with the subject and/or parent/legal representative.
REDACTED COPY 
consultation with the subject and/or parent/legal representative.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2mg/kg/day 
4mg/kg/day 
6mg/kg/day 
6mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2mg/kg/day 
4mg/kg/day 
6mg/kg/day 
6mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
100mg/day 
200mg/day 
300mg/day 
300mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
100mg/day 
200mg/day 
300mg/day 
300mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2) will be used to determine dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2) will be used to determine dose throughout the study.
will be required for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be required for 
for subjects
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
for subjectswho complete the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
who complete the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
label extension study (EP0034).
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
label extension study (EP0034).
provides the taper steps based on the dose of LCM (or matching placebo) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
provides the taper steps based on the dose of LCM (or matching placebo) 
. Whenever possible, these cases 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. Whenever possible, these cases 
medical monitor prior to withdrawing the subject from the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
medical monitor prior to withdrawing the subject from the 
criteria have been met. In case of an 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
criteria have been met. In case of an 
, a faster taper is permitted after discussion with the medical monitor, whenever 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, a faster taper is permitted after discussion with the medical monitor, whenever 
 not be required for some subjects who 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 not be required for some subjects who 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, depending on the treatment option selected by the investigator in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, depending on the treatment option selected by the investigator in 
consultation with the subject and/or parent/legal representative.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
consultation with the subject and/or parent/legal representative.


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 42of 97
Table7‒5: Taper Period dosing ofLCM (or matching placebo)
LCM (or matching 
placebo) dose 
achieved
LCM (or matching placebo) doses for the Taper Period
Week 17
Week 18
Week 19
Week 20
11or 12mg/kg/day
9mg/kg/day 
6mg/kg/day 
4mg/kg/day 
2mg/kg/day
9 or 10mg/kg/day
8mg/kg/day 
6mg/kg/day 
4mg/kg/day 
2mg/kg/day
7 or 8mg/kg/day
6mg/kg/day 
4mg/kg/day 
2mg/kg/day 
2mg/kg/day
5 or 6mg/kg/day
4mg/kg/day 
2mg/kg/day 
2mg/kg/day
NA
3 or 4mg/kg/day
2mg/kg/day 
2mg/kg/day
NA
NA
2mg/kg/day
NA
NA
NA
NA
350 or 400mg/day
300mg/day 
200mg/day 
100mg/day 
100mg/day
250 or 300 mg/day
200mg/day 
100mg/day 
100mg/day
NA
150 or 200mg/day
100mg/day 
100mg/day
NA
NA
100mg/day
NA
NA
NA
NA
LCM=lacosamide; NA=not applicable (taper not required)
Note: The oral solution is dosed as mg/kg/day and tablets are dosed as mg/day.
Note: Subjects not requiring taper will enter directly into the Safety Follow-Up Period and not attend any Taper 
Period visits.
Note: The subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout the study.
Note: The study week numbers providedare for subjects who complete the Maintenance Period and enter the 
Taper Period. The study week numbers provided do not apply to subjects who enter the Taper Period at other 
times.
7.3
Packaging
Lacosamide (tablets and oral solution) and matching placebos are manufactured, packaged, 
and labeled according to Good Manufacturing Practice (GMP) guidelines and applicable laws 
or regulations. The IMP is suitably packaged in such a way as to protect the IMP from 
deterioration during transport and storage.
Lacosamide tablets and matching placebos will be packaged in HDPE bottles.
Lacosamide 10mg/mL oral solution and matching placebo will be packaged in amber PET 
bottles, and will be measured and administered via a dosing syringe.
7.4 
Labeling
Clinical drug supplies will be labeled in accordance with the ICH guidelines on Good 
Clinical Practice (GCP) and GMP and will include any locally required statements. If 
necessary, labels will be translated into the local language.
7.5
Handling and storage requirements
The investigator (or designee) is responsible for the safe and proper storage of IMP at the 
site. The IMPstored by the investigator is to be kept in a secured area with limited access.
The IMP is to be stored according to the instructions on the label. Appropriate storage 
conditions must be ensured either by controlled room temperature, or by completion of a
temperature log (showing minimum and maximum temperatures reached over the time 
interval) in accordance with local requirements on a regular basis.
REDACTED COPY 
2) will be used to determine dose throughout the study.
REDACTED COPY 
2) will be used to determine dose throughout the study.
are for subjects who complete the Maintenance Period and enter the 
REDACTED COPY 
are for subjects who complete the Maintenance Period and enter the 
do n
REDACTED COPY 
do not apply to subjects who enter the Taper Period at other 
REDACTED COPY 
ot apply to subjects who enter the Taper Period at other 
Lacosamide (tablets and oral solution) and matching placebos are manufactured, packaged, 
REDACTED COPY 
Lacosamide (tablets and oral solution) and matching placebos are manufactured, packaged, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
6mg/kg/day 
4mg/kg/day 
2mg/kg/day 
2mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
6mg/kg/day 
4mg/kg/day 
2mg/kg/day 
2mg/kg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
NA
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
NA
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
NA
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
NA
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
NA
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
NA
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
300mg/day 
200mg/day 
100mg/day 
100mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
300mg/day 
200mg/day 
100mg/day 
100mg/day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
NA
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
NA
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ral solution is dosed as mg/kg/day and tablets are dosed as mg/day.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ral solution is dosed as mg/kg/day and tablets are dosed as mg/day.
Note: Subjects not requiring taper will enter directly into the Safety Follow
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Note: Subjects not requiring taper will enter directly into the Safety Follow-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-Up Period and not attend any Taper 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Up Period and not attend any Taper 
2) will be used to determine dose throughout the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2) will be used to determine dose throughout the study.
are for subjects who complete the Maintenance Period and enter the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
are for subjects who complete the Maintenance Period and enter the 
ot apply to subjects who enter the Taper Period at other 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ot apply to subjects who enter the Taper Period at other 
Lacosamide (tablets and oral solution) and matching placebos are manufactured, packaged, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Lacosamide (tablets and oral solution) and matching placebos are manufactured, packaged, 
and labeled according to Good Manufacturing Practice (GMP) guidelines and applicable laws 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
and labeled according to Good Manufacturing Practice (GMP) guidelines and applicable laws 
regulations. The IMP is suitably packaged in such a way
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
regulations. The IMP is suitably packaged in such a way
deterioration during transport and storage.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
deterioration during transport and storage.
Lacosamide tablets and matching placebos will be packaged in HDPE bottles.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Lacosamide tablets and matching placebos will be packaged in HDPE bottles.
Lacosamide 10mg/mL oral solution and matching placebo 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Lacosamide 10mg/mL oral solution and matching placebo 
bottles, and will be measured and administered via a dosing sy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
bottles, and will be measured and administered via a dosing sy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Labeling
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Labeling
Clinical drug supplies will be labeled in accordance with the I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Clinical drug supplies will be labeled in accordance with the I
Clinical Practice (GCP) and GMP and will include any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Clinical Practice (GCP) and GMP and will include any
necessary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
necessary, labels will be translated into the local language.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, labels will be translated into the local language.
7.5
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
7.5
The investigator (or designee) is responsible for the safe and proper storage of IMP at the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The investigator (or designee) is responsible for the safe and proper storage of IMP at the 
site. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
site. 


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 43of 97
In case an out-of-range temperature is noted, it must be immediately communicated to the 
sponsor’s designee in accordance with the pharmacy manual.
The investigator (or designee) will instruct the subject to store the IMP following the 
instructions on the label.
7.6
Drug accountability
A Drug Accountability form will be used to record IMP dispensing and return information on 
a by-subject basis and will serve as source documentation during the course of the study. 
Details of any IMP lost (due to breakage or wastage), not used, disposed of at the study site, 
or returned to the sponsor’sdesignee 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 IMP until returned.
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 the IMP 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) and unused IMP containers must be reconciled and returned to UCB‘s
designee, preferably in their original package. The IMP intended for the study cannot be used 
for any other purpose than that described in this protocol.
7.7
Procedures for monitoring subject compliance
At each visit after IMP is dispensed, subjects must return all used, unused,and empty IMP 
containers. Drug accountability must be done in the subject’s presence in order to obtain 
explanations regarding discrepancies in compliance with the dosing regimen. Drug 
accountability must be recorded on the Drug Accountability Form.
If a subject is found to be persistently noncompliant (defined as less than 75% or more than 
125% compliant with the dosage schedule), the sponsor, in conjunction with the investigator, 
will make a decision as to whether the subject should be withdrawn from the study.
Timely completion of the subject diary is essential for evaluation of safety and efficacy. 
Subject diary usewill be confirmed at each visit and telephone contact. 
7.8
Concomitant medications/treatments
7.8.1 
Permitted and prohibited concomitant treatments (medications 
and therapies)
Subject must have been maintained on a stable dose regimen of 1 to ≤3marketed AEDs for 
≥4weeks prior to Visit1 (ie, prior to entry into the Baseline Period); the dose regimen of the 
AEDs must be kept stable throughout study participation.
Vagal nerve stimulation is allowed and will not be counted as a concomitant AED. The VNS 
device must implanted for ≥6 months before Visit1, and the devicesettings must be stable 
REDACTED COPY 
The investigator must ensure that the IMP is used only
REDACTED COPY 
The investigator must ensure that the IMP is used only in accordance with the protocol.
REDACTED COPY 
 in accordance with the protocol.
The investigator must ensure that the IMP is used only in accordance with the protocol.
The investigator must ensure that the IMP is used only
REDACTED COPY 
The investigator must ensure that the IMP is used only in accordance with the protocol.
The investigator must ensure that the IMP is used only
, and/or after completion of the clinical phase of the study
REDACTED COPY 
, and/or after completion of the clinical phase of the study
 containers) and unused IMP containers must be reconciled and returned to UCB
REDACTED COPY 
 containers) and unused IMP containers must be reconciled and returned to UCB
y in their original package. 
REDACTED COPY 
y in their original package. The I
REDACTED COPY 
The I
REDACTED COPY 
y other purpose than that described in this protocol.
REDACTED COPY 
y other purpose than that described in this protocol.
Procedures for monitoring subject compliance
REDACTED COPY 
Procedures for monitoring subject compliance
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rmation on 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rmation on 
IMP lost (due to breakage or wastage), not used, disposed of at the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
IMP lost (due to breakage or wastage), not used, disposed of at the study site, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 site, 
IMP lost (due to breakage or wastage), not used, disposed of at the study site, 
IMP lost (due to breakage or wastage), not used, disposed of at the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
IMP lost (due to breakage or wastage), not used, disposed of at the study site, 
IMP lost (due to breakage or wastage), not used, disposed of at the study
on the appropriate forms. All 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
on the appropriate forms. All 
 documentation must be made available throughout the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 documentation must be made available throughout the study for UCB 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 for UCB 
 documentation must be made available throughout the study for UCB 
 documentation must be made available throughout the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 documentation must be made available throughout the study for UCB 
 documentation must be made available throughout the study
The investigator (or designee) is responsible for retaining all used, unused, and partiall
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The investigator (or designee) is responsible for retaining all used, unused, and partiall
 assign some of the investigator’s duties for drug accountability
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 assign some of the investigator’s duties for drug accountability
 in accordance with the protocol.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 in accordance with the protocol.
, and/or after completion of the clinical phase of the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, and/or after completion of the clinical phase of the study
 containers) and unused IMP containers must be reconciled and returned to UCB
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 containers) and unused IMP containers must be reconciled and returned to UCB
The I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The IMP
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
MP
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y other purpose than that described in this protocol.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y other purpose than that described in this protocol.
Procedures for monitoring subject compliance
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Procedures for monitoring subject compliance
At each visit after IMP is dispensed, subjects must return all 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
At each visit after IMP is dispensed, subjects must return all 
 must be done in th
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 must be done in th
explanations regarding discrepancies in compliance with the dosing regimen. Drug 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
explanations regarding discrepancies in compliance with the dosing regimen. Drug 
 must be recorded on the Drug Accountability
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 must be recorded on the Drug Accountability
If a subject is found to be persistently
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
If a subject is found to be persistently
125% compliant with the dosage schedule), the sponsor, in conjunction with the investigator, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
125% compliant with the dosage schedule), the sponsor, in conjunction with the investigator, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will make a decision as to whether the subject should be withdrawn from the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will make a decision as to whether the subject should be withdrawn from the study
 completion of the subject diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 completion of the subject diary
Subject diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject diaryuse
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
use
7.8.1
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
7.8.1
Subject must have been maintained on 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject must have been maintained on 


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 44of 97
for ≥4 weeks before Visit 1and be kept stable during the Baseline Period,TreatmentPeriod, 
and Transition Period. Use of the VNS device magnet is allowed.
The following medications/therapies are prohibited during the course of this study:
Neuroleptics
Monoamine oxidase inhibitors
Barbiturates (except as anti-epileptic medications)
Narcotic analgesics
Subjects who have been treated with vigabatrin and experienced any vision loss are excluded 
from the study. Subjects who have received vigabatrin in the past must have documentation 
of an assessment for vision loss prior to study entry or documentation of why visual field 
testing cannot be performed.
Subjects who have been treated with felbamate and have experienced any serious toxicity 
issues (defined as liver failure, aplastic anemia) with this treatment are excluded from the 
study. Subjects treated with felbamate for <12months are also excluded. Any subject who 
has been treated with felbamate for ≥12 months and has not experienced serious toxicity 
issues is eligible for the study.
The following medications are not allowed unless used as described:
Amphetamines and sedative antihistamines: stable use only.
Anxiolytics or once-daily hypnotics: stable, low doses of for nonepilepsy indications
only.
The chronic use of benzodiazepines is allowed for treatment of epilepsy. Benzodiazepines 
taken for treatment of epilepsy will be counted as 1 of the AEDs, and the dose regimen must 
be stable for ≥28days prior to Visit1. Intermittent use of benzodiazepines as rescue therapy 
for epilepsy is allowed if taken at a maximum frequency of 1 day per month (with up to 
3 doses within 24hours).
Therapy that 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 a therapy that is expressly not 
permitted. In cases where this occurs but withdrawal criteria have not been met, the 
advisability of the subject’s continuation in the study must be discussed between the Medical 
Monitor and the investigator.
7.8.2 
Rescue medication
The use of benzodiazepines as rescue therapy for epilepsy is allowed if taken at a maximum 
frequency of one day per month (with ≤3doses within 24 hours) during study participation; 
more frequent use precludes subjects from study participation.
7.9 
Blinding
Subjects, investigators, and all site personnel are blinded to study medication.
REDACTED COPY 
months and has not experienced serious toxicity
REDACTED COPY 
months and has not experienced serious toxicity
The following medications are not allowed unless 
REDACTED COPY 
The following medications are not allowed unless used as described:
REDACTED COPY 
used as described:
Amphetamines and sedative antihistamines
REDACTED COPY 
Amphetamines and sedative antihistamines: stable use only
REDACTED COPY 
: stable use only
y hypnotics
REDACTED COPY 
y hypnotics:
REDACTED COPY 
:stable, low doses of 
REDACTED COPY 
stable, low doses of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y vision loss are excluded 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y vision loss are excluded 
. Subjects who have received vigabatrin in the past must have documentation 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. Subjects who have received vigabatrin in the past must have documentation 
 or documentation of why
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 or documentation of why visual field 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 visual field 
 or documentation of why visual field 
 or documentation of why
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 or documentation of why visual field 
 or documentation of why
Subjects who have been treated with felbamate and have experienced an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subjects who have been treated with felbamate and have experienced any s
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y s
issues (defined as liver failure, aplastic anemia) with this treatment are excluded from the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
issues (defined as liver failure, aplastic anemia) with this treatment are excluded from the 
months are also excluded. Any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
months are also excluded. Any
months and has not experienced serious toxicity
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
months and has not experienced serious toxicity
used as described:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
used as described:
: stable use only
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
: stable use only
stable, low doses of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
stable, low doses of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The chronic use of benzodiazepines is allowed for treatment of epileps
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The chronic use of benzodiazepines is allowed for treatment of epileps
taken for treatment of epilepsy will be counted as 1 of the AEDs, and the dose regimen must 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
taken for treatment of epilepsy will be counted as 1 of the AEDs, and the dose regimen must 
s prior to Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s prior to Visit1. I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
1. I
y is allowed if taken at a maximum frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y is allowed if taken at a maximum frequency
y that becomes necessary (in the investigator’s opinion) during the course of the stud
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y that becomes necessary (in the investigator’s opinion) during the course of the stud
must not be refused to a subject, even if described above as a therap
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
must not be refused to a subject, even if described above as a therap
permitted. In cases wh
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
permitted. In cases wh
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of the subject’s continuation in the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of the subject’s continuation in the study
Monitor and the investigator.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Monitor and the investigator.
The use of benzodiazepines as rescue therap
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The use of benzodiazepines as rescue therap
frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
frequency
more frequent use precludes subjects from stud
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
more frequent use precludes subjects from stud


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 45of 97
Lacosamide (tablets and oral solution) and matching placebos are tablets identical in shape, 
size, and color. The blind is maintained as the accompanying packaging is identical in 
appearance so that neither the investigator (or designee) nor the subject is able to tell whether 
the subject is receiving LCM or placebo.
An interactive voice/web response system (IXRS) will be used to assign a treatment to 
subjects who meet eligibility criteria at Visit2, based on a predetermined randomization 
schedule. The IXRS is used to control all drug distribution and inventory for this study.
The IXRS will be responsible for subsequent issue of treatment kits, as appropriate to the 
visit schedule.
7.9.1 
Procedures for maintaining and breaking the treatment blind
7.9.1.1
Maintenance of study treatment blind
All subject treatment details will be allocated and maintained by the IXRS.
7.9.1.2
Breaking the treatment blind in an emergency situation
In the event of an emergency, it will be possible to determine to which treatment arm and 
dose the subject has been allocated by contacting the IXRS. All sites will be provided with 
details of how to contact the system for code breaking at the start of the study. The Medical 
Monitor or equivalent should be consulted prior to unblinding, whenever possible.
The CPM will be informed immediately via the IXRS when a code is broken, but will remain 
blinded to specific treatment information. Any unblinding of the IMP performed by the 
investigator must be recorded in the source documents and on the Study Termination CRF 
page.
7.10
Randomization and numbering of subjects
An IXRS will be used for assigning eligible subjects to a treatment regimen based on a 
predetermined randomization schedule provided by UCB BIOSCIENCES. The 
randomization schedule will be produced by a UCB BIOSCIENCES biostatistician who is 
otherwise not involved in this study. The IXRS is responsible for issuing subject kits of study 
medication, as appropriate, according to the visit schedule.
To enroll a subject (Visit 1), the investigator will contact the IXRS and provide brief details 
about the subject to be enrolled. Each subject will receive a 5-digit number assigned at 
Screening which serves as the subject identifier throughout the study. The subject number 
will be required in all communication between the investigator (or designee) and the IXRS 
regarding a particular subject. Subject numbers and kit numbers will be tracked via the IXRS. 
To randomize a subject (Visit 2), the investigator (or designee) will contact the IXRS and 
provide brief details about the subject to be randomized. The IXRS will allocate kit numbers 
to the subject based on the subject number during the course of the study.
8
STUDY PROCEDURES BY VISIT
Detailed tabular schedules of study procedures are provided in Section5.2.The subject 
should take concomitant AEDs at the usual time(s) on the morning of each clinic visit.
REDACTED COPY 
stem for code breaking at the start of the study
REDACTED COPY 
stem for code breaking at the start of the study
Monitor or equivalent should be consulted prior to un
REDACTED COPY 
Monitor or equivalent should be consulted prior to unblinding, whenever possible.
REDACTED COPY 
blinding, whenever possible.
 via the IXRS when a code is broken, but will remain 
REDACTED COPY 
 via the IXRS when a code is broken, but will remain 
blinded to specific treatment information. An
REDACTED COPY 
blinded to specific treatment information. Any unblinding of the IMP performed by the 
REDACTED COPY 
y unblinding of the IMP performed by the 
investigator must be recorded in the source document
REDACTED COPY 
investigator must be recorded in the source document
Randomization and numbering of subjects
REDACTED COPY 
Randomization and numbering of subjects
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The IXRS will be responsible for subsequent issue of treatment kits, as appropriate to the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The IXRS will be responsible for subsequent issue of treatment kits, as appropriate to the 
reatment blind
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
reatment blind
 the IXRS.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 the IXRS.
Breaking the treatment blind in an emergency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Breaking the treatment blind in an emergency situation
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 situation
Breaking the treatment blind in an emergency situation
Breaking the treatment blind in an emergency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Breaking the treatment blind in an emergency situation
Breaking the treatment blind in an emergency
In the event of an emergency, it will be possible to determine to which treatment arm and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
In the event of an emergency, it will be possible to determine to which treatment arm and 
y contacting the IXRS. All sites will be provided with 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y contacting the IXRS. All sites will be provided with 
stem for code breaking at the start of the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
stem for code breaking at the start of the study
blinding, whenever possible.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
blinding, whenever possible.
 via the IXRS when a code is broken, but will remain 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 via the IXRS when a code is broken, but will remain 
y unblinding of the IMP performed by the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y unblinding of the IMP performed by the 
investigator must be recorded in the source document
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
investigator must be recorded in the source document
Randomization and numbering of subjects
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Randomization and numbering of subjects
An IXRS will be used for assigning eligible subjects to a treatment regimen based on a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
An IXRS will be used for assigning eligible subjects to a treatment regimen based on a 
predetermined randomization schedule provided by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
predetermined randomization schedule provided by
dule will be produced b
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
dule will be produced b
otherwise not involved in this study. The IXRS is responsible for issuing subject kits of study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
otherwise not involved in this study. The IXRS is responsible for issuing subject kits of study
medication, as appropriate, according to the visit schedule.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
medication, as appropriate, according to the visit schedule.
To enroll a subject (Visit 1), th
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
To enroll a subject (Visit 1), th
about the subject to be enrolled. Each subject will receive a 5
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
about the subject to be enrolled. Each subject will receive a 5
Screening which serves as the subject identifier throughout the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Screening which serves as the subject identifier throughout the study
will be requir
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be required in all communication between the investigator (or designee) and the IXRS 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ed in all communication between the investigator (or designee) and the IXRS 
regarding a particular subject. Subject numbers and kit numbers will be tracked via the IXRS. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
regarding a particular subject. Subject numbers and kit numbers will be tracked via the IXRS. 
To randomize a subject (Visit 2
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
To randomize a subject (Visit 2
provide brief details about the subject to be randomized. The I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
provide brief details about the subject to be randomized. The I
to the subject based on the subject number during the course of the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
to the subject based on the subject number during the course of the study


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 46of 97
At all visits and telephone contacts, subjects will be instructed to call the investigator if any 
intolerable and/or serious AEs occur before the next visit or contact. After subjects begin 
study medication, if any AEs necessitate a subject’s withdrawal from the study, the subject 
should come in for a clinic visit as soon as possible after the occurrence of the AE.
Planned clinic visits should be scheduledas indicated in Section5.2witha window 
of±2days relative to Visit 2 (Baseline Period), with the exception of the Safety Follow-Up 
Visit, which should be scheduled 14days (-1/+3days) after the final dose of study 
medication.
The subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout the 
study.
8.1
Baseline Period: Week-8to Week0
8.1.1 
Baseline Period: Visit1 (Week-8) (Screening)
At Visit 1, subjects will be evaluated for their suitability for enrollment. It is acceptable for 
this visit to be conducted on more than 1day; however, all results of Visit 1 assessments 
should be available before T1. Prior to the conduct of any study-related procedures, a 
complete explanation (both verbal and written) of the nature and purpose of the study will be 
given to the subject by the investigator (or designee). The subject or parent/legal 
representative is required to sign and date the IRB/IEC-approved informed consent if he/she 
decides to participate in the study.
The subject’s eligibility for the study will be determined on the basis of the 
inclusion/exclusion criteria, signature of an informed consent prior to any study-related 
procedures or evaluations, and the results of the following pretreatment assessments (for 
further details of the assessments and the required procedures and methods, please refer to 
Section 9, Section10, and Section11of this protocol):
Medical history
Seizure history
Concomitant medications
Concomitant AEDs
VNS assessment (for subjects with an implanted VNS device)
Physical examination (complete)
Tanner Stage assessment
Vital signs (BP and pulse rate, including orthostatic assessments)
Body weight assessment
Height assessment
Head circumference
Neurological examination (complete)
REDACTED COPY 
complete explanation (both verbal and written) of the nature and purpose of the study
REDACTED COPY 
complete explanation (both verbal and written) of the nature and purpose of the study
 the investigator (or designee). The subject or parent/legal 
REDACTED COPY 
 the investigator (or designee). The subject or parent/legal 
representative is required to sign and date the IRB/IEC
REDACTED COPY 
representative is required to sign and date the IRB/IEC
 will be
REDACTED COPY 
 will bedetermined on the basis of the 
REDACTED COPY 
determined on the basis of the 
inclusion/exclusion criteria, signature of an informed consent prior to an
REDACTED COPY 
inclusion/exclusion criteria, signature of an informed consent prior to an
procedures or evaluations, and the results of the following pretreatment assessments (for 
REDACTED COPY 
procedures or evaluations, and the results of the following pretreatment assessments (for 
further details of the assessments and the r
REDACTED COPY 
further details of the assessments and the r
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rmine dose throughout the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rmine dose throughout the 
1, subjects will be evaluated for their suitability for enrollment. It is acceptable for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
1, subjects will be evaluated for their suitability for enrollment. It is acceptable for 
; however, all results of Visit 1 assessments 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
; however, all results of Visit 1 assessments 
y study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y study-related procedures, a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-related procedures, a 
complete explanation (both verbal and written) of the nature and purpose of the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
complete explanation (both verbal and written) of the nature and purpose of the study
 the investigator (or designee). The subject or parent/legal 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 the investigator (or designee). The subject or parent/legal 
representative is required to sign and date the IRB/IEC
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
representative is required to sign and date the IRB/IEC-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-approved informed consent if he/she 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
approved informed consent if he/she 
determined on the basis of the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
determined on the basis of the 
inclusion/exclusion criteria, signature of an informed consent prior to an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
inclusion/exclusion criteria, signature of an informed consent prior to an
procedures or evaluations, and the results of the following pretreatment assessments (for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
procedures or evaluations, and the results of the following pretreatment assessments (for 
further details of the assessments and the r
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
further details of the assessments and the r
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
equired procedures and m
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
equired procedures and m
11
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
11of this protocol):
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
of this protocol):
Concomitant medications
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant medications
Concomitant AEDs
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant AEDs
asses
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
assessment
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sment
sical examination (complete)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sical examination (complete)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Tanner Stage assessment
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Tanner Stage assessment
Vital signs (BP and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Vital signs (BP and 

This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 



UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 47of 97
12-lead ECG (2 interpretable recordings [20 to 30 minutes apart] to be performed prior to 
any blood draws and vital signs assessment and,if possible,with the subject in the supine 
positionfor approximately 5minutes precedingthe recordings and during the recordings)
Blood sample for clinical chemistry and hematology
Urine sample for urinalysis(for subjects ≥5 years of age)
Serum pregnancy test (for females of childbearing potential)
Blood sample for measurement of concomitant AED plasma concentrations
Blood sample for measurement of LCM plasma concentration
C-SSRS(for subjects ≥6years of age)
Contact IXRS to obtain unique subject identification number
Dispense subject diary
AE reporting
Assessments of subject’s candidacy for epilepsy surgery/VNS
Health care resource use
The subject will be scheduled to return to the clinic as specified in Table 5-1. The morning of 
the next clinic visit, the subject should take concomitant AEDs at the usual time(s).
8.1.2 
Baseline Period: Telephone Contact 1 (Week-4)
If the subject is eligible to continue in the study, the following assessments will be 
performed:
Concomitant medications
Concomitant AEDs
Reminder to complete subject diary on a daily basis
Review withdrawal criteria
AE reporting
8.1.3 
Baseline Period: Visit2 (Week 0) (Randomization)
At the beginning of this visit, the investigator should assess the partial-onset seizure 
frequency over the 8-week Baseline Period as recordedin the subject diary. On the basis of 
the diary, the subject must have reported at least 2partial-onset seizures per 28days on 
average, with no more than 21 consecutive seizure-free days during the 8weeks prior to entry 
into the Baseline Period. During this study, subjects must have reported at least 
2partial-onset seizures during the 8-week prospective Baseline Period to be eligible for 
randomization at Visit 2. If the subject is eligible to continue in thestudy, the following 
assessments will be performed:
Concomitant medications
REDACTED COPY 
The subject will be scheduled to return to the clinic 
REDACTED COPY 
The subject will be scheduled to return to the clinic as specified in 
REDACTED COPY 
as specified in 
clinic visit, the subject should take concomitant AEDs
REDACTED COPY 
clinic visit, the subject should take concomitant AEDs
Telephone Contact 1
REDACTED COPY 
Telephone Contact 1
If the subject is eligible to continue in the study
REDACTED COPY 
If the subject is eligible to continue in the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
/VNS
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
/VNS
as specified in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
as specified in 
clinic visit, the subject should take concomitant AEDs
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
clinic visit, the subject should take concomitant AEDs
Telephone Contact 1
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Telephone Contact 1
If the subject is eligible to continue in the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
If the subject is eligible to continue in the study, the following assessments will be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, the following assessments will be 
Reminder to complete subject diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Reminder to complete subject diary
Review withdrawal criteria
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Review withdrawal criteria
Baseline Period: Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Baseline Period: Visit
At the beginning of this visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
At the beginning of this visit
frequenc
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
frequency over the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y over the 
the diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, the subject must have reported at least 2
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, the subject must have reported at least 2
average, with no more than 21
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
average, with no more than 21
into the Baseline Period. During this stud
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
into the Baseline Period. During this stud
2
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2


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 48of 97
Concomitant AEDs
VNS assessments (for subjects with an implanted VNS device)
Physical examination (complete)
Vital signs (BP and pulse rate, including orthostatic assessments)
Body weight assessment
Height assessment
Neurological examination (complete)
12-lead ECG (2 interpretable recordings [20 to 30 minutes apart] to be performed prior to 
any blood draws and vital signs assessment and,if possible,with the subject in the supine 
position for approximately 5 minutes preceding the recordings and during the recordings)
Blood sample for clinical chemistry and hematology
Blood sample for endocrinology
Urine sample for urinalysis(for subjects ≥5 years of age)
Urine pregnancy test (for females of childbearing potential)
C-SSRS(for subjects ≥6years of age)
Achenbach CBCL 
BRIEF-P/BRIEF score
PedsQL score
Contact IXRS
Randomization
Dispense study medication
Reminder to complete subject diary on a daily basis
Review withdrawal criteria
AEreporting
Health care resource use
The subject will take the first dose of study medication in the clinic. The subject will be 
scheduled to return to the clinic as specified in Table5-1. On the morning of the next clinic 
visit, the subject should take concomitant AEDs and study medication at the usual time(s).
8.2
Titration Period: Week1 to Week6
Both clinic visits and telephone contacts will be conducted during the Titration Period, 
beginning with Telephone Contact 2 at the end of Week1 and continuing throughVisit5at 
the end of Week6. The subject should take concomitant AEDs and study medication at the 
usual time(s) on the morning of each clinic visit.
REDACTED COPY 
females of childbearing potential)
REDACTED COPY 
females of childbearing potential)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
to be performed prior to 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
to be performed prior to 
with the subject in the supine 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
with the subject in the supine 
and during the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
and during the 
females of childbearing potential)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
females of childbearing potential)
 medication
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 medication
Reminder to complete subject diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Reminder to complete subject diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Review withdrawal criteria
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Review withdrawal criteria
reporting
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
reporting
Health care resource use
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Health care resource use
The subject will take the first dose of study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject will take the first dose of study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
scheduled to return to the clinic 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
scheduled to return to the clinic 
visit, the subject should take concomitant AEDs and study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
visit, the subject should take concomitant AEDs and study
8.2
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8.2


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05Mar 2015
Clinical Study Protocol
Lacosamide
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Confidential
Page 49of 97
At each clinic visit and telephone contact, the investigator, in conjunction with the subject 
and/or parent(s)/legal representative(s), will decide how to proceed with study medication 
dosing based on tolerability (including vital signs, body weight, 12-lead ECG, and AE 
reporting, as applicable to the type of contact). If the withdrawal of study medication is 
required during the Titration Period, the subject will enter the blindedTaper Period 
(Section8.5).
8.2.1 
Titration Period: Telephone Contact2 (Week1), Telephone 
Contact 3 (Week 3),and Telephone Contact 4 (Week5)
During the Titration Period telephone contacts (Telephone Contact 2, Telephone Contact 3,
and Telephone Contact4),the following assessments will be performed:
Concomitant medications
Concomitant AEDs
Reminder to complete subject diary on a daily basis
Review withdrawal criteria
AE reporting
8.2.2 
Titration Period: Visit3 (Week2), Visit4 (Week4), and Visit 5
(Week6)
During the Titration Period clinic visits (Visit3,Visit4, and Visit5), the following 
assessments will be performed:
Concomitant medications
Concomitant AEDs
VNS assessment (for subjects with an implanted VNS device)
Physical examination (brief) 
Vital signs (BP and pulserate, including orthostatic assessments)
Body weight assessment
Neurological examination (brief) 
12-lead ECG (2 interpretable recordings [20 to 30 minutes apart] to be performed prior to 
any blood draws and vital signs assessment and, if possible,with the subject in the supine 
position for approximately 5 minutes preceding the recordings and during the recordings)
Blood sample for clinical chemistry and hematology(Visit4 and Visit 5 only)
Urine sample for urinalysis(for subjects ≥5 years of age) (Visit 4 and Visit 5 only)
Serum pregnancy test (for females of childbearing potential) (Visit4 and Visit5 only)
Urine pregnancy test (for females of childbearing potential) (Visit3 only)
Blood sample for determination of concomitant AED plasma concentration (Visit5 only)
REDACTED COPY 
2)
REDACTED COPY 
2),
REDACTED COPY 
,Visit
REDACTED COPY 
Visit
Visit
REDACTED COPY 
Visit3
REDACTED COPY 
3Visit
REDACTED COPY 
Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, Telephone Contact
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, Telephone Contact3
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
3
Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Visit4 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
4 
Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Visit4
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
4
for subjects with an implanted VNS device
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
for subjects with an implanted VNS device
sical examination (brief) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sical examination (brief) 
pulse
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
pulse
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rate
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rate
y weight assessment
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y weight assessment
Neurological examinati
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Neurological examinati
lead ECG 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
lead ECG (2 interpretable recordings [20 to 30 minutes apart] 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(2 interpretable recordings [20 to 30 minutes apart] 
 blood draws and vital signs assessment and
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 blood draws and vital signs assessment and
position for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
position for 
Blood sample for clinical chemistry
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Blood sample for clinical chemistry

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


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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 50of 97
Blood sample for determination of LCM plasma concentration (Visit 5 only)
C-SSRS(for subjects ≥6years of age)
Achenbach CBCL (same version used at Visit 2)(Visit 5 only)
Contact IXRS
Dispense study medication
Study medication return
Reminder to complete subject diary on a daily basis
Review withdrawal criteria
AE reporting
Health care resource use
The subject will be scheduled to return to the clinic as specified in Table 5-1. The morning of 
the next clinic visit, the subject should take concomitant AEDs and study medication at the 
usual time(s).
8.3
Maintenance Period: Week7to Week16
Subjects who complete the Titration Period will enter the 10-week Maintenance Period at the 
study medication dose they received on the finalday of the Titration Period. Dose reduction 
is not allowed during the Maintenance Period; subjects who require dose reduction during the 
Maintenance Period will be withdrawn from the study. Subjects who are withdrawn will enter 
the Taper Period (see Section7.2.4).
Beginning with Visit6 at the end of Week 8 and continuing up to Visit8at the end of 
Week 16, alternating telephone contacts and clinic visits will be co nducted during the 
Maintenance Period. The subject should take concomitant AEDs and study medication at the 
usual time(s) on the morning of each clinic visit.
8.3.1
Maintenance Period: Visit6 (Week8)and Visit7 (Week12)
During Visit 6and Visit7(clinic visits) of the Maintenance Period, the following 
assessments will be performed:
Concomitant medications
Concomitant AEDs
VNS assessments (for subjects with an implanted VNS device)
Physical examination (brief)
Vital signs (BP and pulserate; including orthostatic assessments)
Body weight assessment
Neurological examination (brief)
REDACTED COPY 
to Week
REDACTED COPY 
to Week
Titration Period will enter
REDACTED COPY 
Titration Period will enter
final
REDACTED COPY 
finalday
REDACTED COPY 
day
is not allowed during the Maintenance Period; subjects who require dose reduction during the 
REDACTED COPY 
is not allowed during the Maintenance Period; subjects who require dose reduction during the 
Maintenance Period will be withdrawn from the study
REDACTED COPY 
Maintenance Period will be withdrawn from the study
).
REDACTED COPY 
).
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Table
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Table5
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5
bject should take concomitant AEDs and study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
bject should take concomitant AEDs and study
to Week
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
to Week
Titration Period will enter
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Titration Period will enterthe 10
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the 10
day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
day of the Titration Period. Dose reduction 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of the Titration Period. Dose reduction 
day of the Titration Period. Dose reduction 
day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
day of the Titration Period. Dose reduction 
day
is not allowed during the Maintenance Period; subjects who require dose reduction during the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
is not allowed during the Maintenance Period; subjects who require dose reduction during the 
Maintenance Period will be withdrawn from the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Maintenance Period will be withdrawn from the study
Week
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Week
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
8
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
8
16, alternating telephone contacts and clinic visits will be conducted during the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
16, alternating telephone contacts and clinic visits will be conducted during the 
The subject should take concomitant AEDs and study medication at the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject should take concomitant AEDs and study medication at the 
usual time(s) on the morning of each clinic visit.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
usual time(s) on the morning of each clinic visit.
Maintenance Period: Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Maintenance Period: Visit
Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Visit7(
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
7(
assessments will be performed:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
assessments will be performed:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant medications
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant medications
Concomitant AEDs
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant AEDs
VNS 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
VNS assessments (for subjects with an implanted VNS device)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
assessments (for subjects with an implanted VNS device)

This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Phy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Phy

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


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 51of 97
12-lead ECG (2 interpretable recordings [20 to 30 minutes apart] to be performed prior to 
any blood draws and vital signs assessment and,if possible,with the subject in the supine 
position for approximately 5 minutes preceding the recordings and during the recordings)
Blood sample for clinical chemistry and hematology(Visit 7 only)
Urine sample for urinalysis(for subjects ≥5 years of age) (Visit7 only)
Serum pregnancy test (for females of childbearing potential) (Visit7 only)
Urine pregnancy test (for females of childbearing potential) (Visit6 only)
C-SSRS(for subjects ≥6years of age)
Contact IXRS
Dispense study medication
Study medication return
Reminderto complete subject diary on a daily basis
Review withdrawal criteria
AE reporting
Health care resource use
The subject will be scheduled to return to the clinic as specified in Table 5-1. The morning of 
the next clinic visit, the subject should take concomitant AEDs and study medication at the 
usual time(s).
8.3.2 
Maintenance Period: Telephone Contact5 (Week10) and 
Telephone Contact6 (Week14)
During the Maintenance Period telephone contacts (Telephone Contact 5 and Telephone 
Contact6);the following assessments will be performed:
Concomitant medications
Concomitant AEDs
Reminder to complete subject diary on a daily basis
Review withdrawal criteria
AE reporting
8.3.3 
End of Maintenance Period: Visit 8(Week16)
For subjects who complete the Maintenance Period, Visit 8 will be the final Maintenance 
Period clinic visit.
At the completion of the Maintenance Period, investigators should discuss treatment options 
with the subject and/or their parent/legal representative to best manage the subject’s epilepsy. 
Subjects who have completed the 10-week Maintenance Period will be given the opportunity 
to enroll in an open-label extension LCM study(EP0034). The decision made by the subject
REDACTED COPY 
The subject will be scheduled to return to the clinic 
REDACTED COPY 
The subject will be scheduled to return to the clinic 
the next clinic visit, the subject should take concomitant AEDs and study
REDACTED COPY 
the next clinic visit, the subject should take concomitant AEDs and study
Maintenance Period: Telephone Contact
REDACTED COPY 
Maintenance Period: Telephone Contact
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject will be scheduled to return to the clinic 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject will be scheduled to return to the clinic as specified in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
as specified in 
the next clinic visit, the subject should take concomitant AEDs and study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the next clinic visit, the subject should take concomitant AEDs and study
Maintenance Period: Telephone Contact
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Maintenance Period: Telephone Contact
act
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
act6 (Week
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
6 (Week
During the Maintenance Period telephone contacts (Telephone Contact
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
During the Maintenance Period telephone contacts (Telephone Contact
the following assessments will be performed:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the following assessments will be performed:
Concomitant medications
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant medications
Concomitant AEDs
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant AEDs
Reminder to complete subject diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Reminder to complete subject diary
withdrawal criteria
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
withdrawal criteria
AE reporting
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
AE reporting
8.3.3
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
8.3.3
For subjects who complete the Maintenance Period, Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
For subjects who complete the Maintenance Period, Visit
Period clinic visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Period clinic visit


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 52of 97
or parent(s)/legal representative(s) and investigator regarding participation in the open-label 
extension study will be recorded in the IXRS and in the CRF. Subjects who plan to enroll in 
the open-label extensionstudy will enter a 4-week blinded Transition Period. 
Subjects who choose not to participate in the open-label extension study (EP0034) will enter 
a blinded Taper Period (2to 4weeks, depending on dose level achieved) (see Section8.5)
after completing Visit 8. Taper of LCM may not be required for some subjects who complete 
the Maintenance Period depending on the treatment option selected by the investigator in 
consultation with the subject and/or parent/legal guardian. These subjects should complete 
Visit8 andthen complete the 30-day Safety Follow‑Up Period after Visit 8(see Section8.6); 
the Taper Visit is not required for subjects who complete the Maintenance Period and who do
not undergo taper of LCM.
During Visit 8, the following assessments will be performed:
Concomitant medications
Concomitant AEDs
VNS assessment (for subjects with an implanted VNS device)
Physical examination (complete)
Tanner Stage assessment
Vital signs (BP and pulserate, including orthostatic assessments)
Body weight assessment
Height assessment
Head circumference
Neurological examination (complete)
12-lead ECG (2 interpretable recordings [20 to 30 minutes apart] to be performed prior to 
any blood draws and vital signs assessment and,if possible,with the subject in the supine 
positionfor approximately 5 minutes preceding the recordings and during the recordings)
Blood sample for clinical chemistry and hematology
Blood sample for endocrinology
Urine sample for urinalysis(for subjects ≥5 years of age)
Serum pregnancy test (for females of childbearing potential)
Blood sample for measurement of concomitant AED plasma concentrations
Blood sample for measurement of LCM plasma concentration
C-SSRS(for subjects ≥6years of age)
Clinical Global Impression of Change
Caregiver’s Global Impression of Change
REDACTED COPY 
, including orthostatic assessments)
REDACTED COPY 
, including orthostatic assessments)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
hese subjects should complete 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
hese subjects should complete 
(see Section
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(see Section8.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
8.6
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
6
the Taper Visit is not required for subjects who complete the Maintenance Period and who do
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the Taper Visit is not required for subjects who complete the Maintenance Period and who do
assessment (for subjects with an implanted VNS device)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
assessment (for subjects with an implanted VNS device)
, including orthostatic assessments)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, including orthostatic assessments)
Neurological examination (complete)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Neurological examination (complete)
(2 interpretable recordings [20 to 30 minutes apart] 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(2 interpretable recordings [20 to 30 minutes apart] 
 blood draws and vital signs assessment and,
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 blood draws and vital signs assessment and,
approximately
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
approximately
Blood sample for clinical chemistry
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Blood sample for clinical chemistry
Blood sample for endocrinology
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Blood sample for endocrinology
Urine sample for urinal
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Urine sample for urinal
Serum pregnancy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Serum pregnancy
Blood sample for measurement of concomitant AED plasma concentrations
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Blood sample for measurement of concomitant AED plasma concentrations

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


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 53of 97
Achenbach CBCL (same version used at Visit 2)
BRIEF-P/BRIEF score (same version used at Visit2)
PedsQL score (same version used at Visit 2)
Contact IXRS
Dispense study medicationfor the following 4-week Transition Period or Taper Period (2
to 4weeks), as applicable
Study medication return
Reminder to complete subject diary on a daily basis
Review withdrawal criteria
AE reporting
Health care resource use
Subjects who plan to enroll in EP0034, will be scheduled to return to the clinic as specified in 
Table 5-2and subjects who do not plan to enroll in EP0034 will be scheduled to return to the 
clinic as specified in Table5-3. Subjects who do not plan to enter either the Transition Period 
or the Taper Period due to other treatment choices, should be scheduled to return for a Safety 
Follow-Up Visit as specified in Table 5-3. The morning of the next clinic visit, the subject 
should take concomitant AEDs and study medication at the usual time(s).
8.4
Transition Period
Subjects who complete the Maintenance Period and plan to participate in EP0034 will enter a 
blinded Transition Period of 4weeks.
8.4.1
Transition Period: Transition Visit1 (Week17), Transition Visit2 
(Week18), and Transition Visit 3 (Week19)
During Transition Visit 1, Transition Visit 2, and Transition Visit 3 (clinic visits), the 
following assessments will be performed:
Concomitant medications
Concomitant AEDs
VNS assessments (for subjects with an implanted VNS device)
Physical examination (brief) 
Vital signs (BP and pulse rate; including orthostatic assessments)
Body weight assessment
Neurological examination (brief)
C-SSRS (for subjects ≥6years of age)
Contact IXRS
Dispense study medication
REDACTED COPY 
. Subjects who do not plan to enter either the Transition Period 
REDACTED COPY 
. Subjects who do not plan to enter either the Transition Period 
Period due to other treatment choices, should be scheduled to return for a Safet
REDACTED COPY 
Period due to other treatment choices, should be scheduled to return for a Safet
The morning of the next cl
REDACTED COPY 
The morning of the next cl
 medication at the usual time(s).
REDACTED COPY 
 medication at the usual time(s).
Subjects who complete the Maintenance Period and 
REDACTED COPY 
Subjects who complete the Maintenance Period and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-week Transition Period or Taper Period (2
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-week Transition Period or Taper Period (2
Subjects who plan to enroll in EP0034, will be scheduled to return to the clinic as specified in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subjects who plan to enroll in EP0034, will be scheduled to return to the clinic as specified in 
0034 will be scheduled to return to the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
0034 will be scheduled to return to the 
. Subjects who do not plan to enter either the Transition Period 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. Subjects who do not plan to enter either the Transition Period 
Period due to other treatment choices, should be scheduled to return for a Safet
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Period due to other treatment choices, should be scheduled to return for a Safet
The morning of the next cl
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The morning of the next cl
 medication at the usual time(s).
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 medication at the usual time(s).
Subjects who complete the Maintenance Period and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subjects who complete the Maintenance Period and 
eriod: T
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
eriod: Transition
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ransition
, and Transition Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, and Transition Visit
Transition Visit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Transition Visit
following assessments will be performed:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
following assessments will be performed:
Concomitant medications
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant medications
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant AEDs
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Concomitant AEDs
VNS assessments (for subjects with an implanted VNS device)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
VNS assessments (for subjects with an implanted VNS device)
Phy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Physical examination (brief) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sical examination (brief) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Vital signs (BP and pulse rate; including orthostatic assessments)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Vital signs (BP and pulse rate; including orthostatic assessments)

This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Bod
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Bod


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 54of 97
Study medication return
Reminder to complete subject diary on a daily basis
Review withdrawal criteria
AE reporting
Health care resource use
8.4.2 
Transition Period: Transition Visit 4(Week20)
During Transition Visit4 (clinic visit), the following assessments will be performed:
Concomitant medications
Concomitant AEDs
VNS assessment (for subjects with an implanted VNS device)
Physical examination (complete)
Vital signs (BP and pulse rate, including orthostatic assessments)
Body weight assessment
Neurological examination (complete)
12-lead ECG (2 interpretable recordings [20 to 30 minutes apart] to be performed prior to 
any blood draws and vital signs assessment and,if possible,with the subject in the supine 
position for approximately 5 minutes preceding the recordings and during the recordings)
Blood sample for clinical chemistry and hematology
Urine sample for urinalysis(for subjects ≥5 years of age)
Urinepregnancy test (for females of childbearing potential)
Blood sample for measurement of concomitant AED plasma concentrations
Blood sample for measurement of LCM plasma concentration
C-SSRS (for subjects ≥6years of age)
Contact IXRS
Study medication return
Subject diary return
Review withdrawal criteria
AE reporting
Health care resource use
8.5
Taper Period
A blinded Taper Period (2to 4 weeks, depending on dose achieved) will be required for 
subjects who discontinue study medication prematurelyand for subjects who complete the 
REDACTED COPY 
lead ECG (2 interpretable recordings [20 to 30 minutes apart] 
REDACTED COPY 
lead ECG (2 interpretable recordings [20 to 30 minutes apart] 
 blood draws and vital signs assessment and,
REDACTED COPY 
 blood draws and vital signs assessment and,
 5 minutes preceding 
REDACTED COPY 
 5 minutes preceding 
Blood sample for clinical chemistry
REDACTED COPY 
Blood sample for clinical chemistry and hematology
REDACTED COPY 
 and hematology
Blood sample for clinical chemistry and hematology
Blood sample for clinical chemistry
REDACTED COPY 
Blood sample for clinical chemistry and hematology
Blood sample for clinical chemistry
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(clinic visit), the following assessments will be performed:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(clinic visit), the following assessments will be performed:
orthostatic assessments)
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orthostatic assessments)
lead ECG (2 interpretable recordings [20 to 30 minutes apart] 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
lead ECG (2 interpretable recordings [20 to 30 minutes apart] 
 blood draws and vital signs assessment and,
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 blood draws and vital signs assessment and,if possible,
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if possible,
 5 minutes preceding 
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 5 minutes preceding 
 and hematology
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 and hematology
(for subjects 
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(for subjects 
 test (for females of childbeari
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 test (for females of childbeari
Blood sample for measurement of concomitant AED plasma concentrations
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Blood sample for measurement of concomitant AED plasma concentrations
Blood sample for measurement of L
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Blood sample for measurement of L
for subjects 
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for subjects 
Contact IXRS
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Contact IXRS
 medication return
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 medication return
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Subject diary
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Subject diary
Review withdrawal c
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Review withdrawal c

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


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 55of 97
Maintenance Period but choose not to enter the open-label extension study (EP0034). Taper 
of LCM may not be required for some subjects who discontinue study medication 
prematurely depending on the treatment option selected by the investigator in consultation 
with the subject and/or parent/legal representative. The Taper Period is not required for 
subjects who complete the Maintenance Period and who do not undergo taper of LCM.
8.5.1 
Taper Period: Telephone Contact7 (Week17)
A telephone contact will be conducted during the first week of the Taper Period. During 
Telephone Contact7, the following assessments will be performed:
Concomitant medications
Concomitant AEDs
Reminder to complete subject diary on a daily basis
Review withdrawal criteria
AE reporting
If any AEs necessitate asubject’s withdrawal from the study, the subject should return for a 
clinic visit as soon as possible after the occurrence of the AE.
8.5.2 
Taper Period: Taper Visit (Week 18, Week 19, or Week20)
Each subject will have only 1 Taper Visit(clinic visit). The Taper Visit will occur at the end 
of the Taper Period (Week18, Week 19, or Week 20, depending on dose level achieved [see 
Table 7‒5])and includethe following assessments:
Concomitant medications
Concomitant AEDs
VNS assessments
Physical examination (brief)
Vitals signs (BP and pulserate, including orthostatic assessments)
Body weight assessment
Neurological examination (brief)
12-lead ECG (2interpretable recordings to be performed prior to any blood draws and 
vital signs assessment and, if possible, with the subject in the supine position for 
approximately 5 minutes preceding the recordings and during the recordings)
Blood sample for clinical chemistry and hematology
Blood sample for endocrinology
Urine sample for urinalysis(for subjects ≥5 years of age)
Serum pregnancy test (for females of childbearing potential)
C-SSRS(for subjects ≥6years of age)
REDACTED COPY 
clinic visit as soon as possible after the occurrence of the AE.
REDACTED COPY 
clinic visit as soon as possible after the occurrence of the AE.
Week
REDACTED COPY 
Week 18, 
REDACTED COPY 
18, 
(clinic visit)
REDACTED COPY 
(clinic visit)
, or Week
REDACTED COPY 
, or Week
the following assessments:
REDACTED COPY 
the following assessments:
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, the subject should return for a 
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, the subject should return for a 
clinic visit as soon as possible after the occurrence of the AE.
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clinic visit as soon as possible after the occurrence of the AE.
18, 
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18, Week
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Week
(clinic visit)
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(clinic visit). 
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. T
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T
, or Week
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, or Week20
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20, depending on dose level achieved [see 
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, depending on dose level achieved [see 
the following assessments:
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the following assessments:
brief
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brief)
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)
brief)
brief
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brief)
brief
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Vitals signs (BP and 
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Vitals signs (BP and 
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pulse
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pulse
y weight assessment
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y weight assessment
Neurological examination (
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Neurological examination (
lead ECG (2
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lead ECG (2
vital signs assessment and, if possible, 
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vital signs assessment and, if possible, 
approximately
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approximately

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Blood sample for clinical chemistry
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Blood sample for clinical chemistry

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


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 56of 97
Contact IXRS
Study medication return
Subject diary return
Review withdrawal criteria
AE reporting
Health care resource use
The subject will be scheduled to return to the clinic for the next as specified in Table 5-3. The 
morning of the next clinic visit, the subject should take concomitant AEDs at the usual 
time(s).
8.6 
Safety Follow-Up Period
There will be a 30-daySafety Follow-Up Period for all subjects who will not beentering
EP0034. 
8.6.1
Safety Follow-Up Visit
The Safety Follow-Up Visit will occur 2 weeks ±2days after the final dose of study 
medication and will include the following assessments: 
Concomitant medications
Concomitant AEDs
VNS assessments (for subjects with an implanted VNS device)
Physical examination (complete)
Vital signs (BP and pulse rate, including orthostatic assessments)
Body weight assessment
Neurological examination (complete)
12-leadECG (2interpretable recordings to be performed prior to any blood draws and 
vital signs assessment and, if possible, with the subject in the supine position for 
approximately 5 minutes preceding the recordings and during the recordings)(only for 
subjects with an abnormal reading at the previous visit)
Blood sample for clinical chemistry and hematology(only for subjects with an abnormal 
value at the previous visit)
Blood sample for endocrinology(only for subjects with an abnormal value at the previous 
visit)
Urine sample for urinalysis (for subjects ≥5 years of age)
Serum pregnancy test (for females of childbearing potential)(only if blood is collected 
for another assessment) 
Urine pregnancy test (only if blood is not collected for another assessment)
REDACTED COPY 
day
REDACTED COPY 
days after the final dose of study
REDACTED COPY 
s after the final dose of study
medication and will include the following assessments: 
REDACTED COPY 
medication and will include the following assessments: 
VNS assessments (for subjects with an implanted VNS device)
REDACTED COPY 
VNS assessments (for subjects with an implanted VNS device)
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5
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5-3
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-3. 
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. T
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T
morning of the next clinic visit, the subject should take concomitant AEDs at the usual 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
morning of the next clinic visit, the subject should take concomitant AEDs at the usual 
will not be
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will not be
s after the final dose of study
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s after the final dose of study
VNS assessments (for subjects with an implanted VNS device)
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VNS assessments (for subjects with an implanted VNS device)
Vital signs (BP and pulse rate, including orthostatic assessments)
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Vital signs (BP and pulse rate, including orthostatic assessments)
Neurological examination (complete)
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Neurological examination (complete)
interpretable recordings to be performed prior to any
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interpretable recordings to be performed prior to any
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vital signs assessment and, if possible, with the subject in the supine position for 
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vital signs assessment and, if possible, with the subject in the supine position for 
approximately
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approximately5
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5minutes preceding the 
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minutes preceding the 
s with an abnormal reading at the previous visit)
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s with an abnormal reading at the previous visit)
Blood sample for clinical chemistry
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Blood sample for clinical chemistry
value at the previous visit)
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value at the previous visit)
Blood sample for endocrinology
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Blood sample for endocrinology
v
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v


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 57of 97
C-SSRS (for subjects ≥6years of age)
AE reporting
Health care resource use
8.6.2
Safety Follow-Up Telephone Contact
The Safety Follow-Up Telephone Contact will occur 30days (-1/+3days) after the final dose 
of study medicationand will include the following assessments:
Concomitant medications
Concomitant AEDs
AE reporting
8.7
Unscheduled Visit
Unscheduled visits may be performed at the investigator’s discretion. The following 
assessments are required:
Concomitant medications
Concomitant AEDs
VNS assessment (for subjects with an implanted VNS device only)
Vital signs (BP and pulserate, including orthostatic assessments)
Body weight assessment
C-SSRS for subjects ≥6years of age(only if visit is relatedto an AE)
Reminder to complete subject diary on a daily basis
Review withdrawal criteria
AE reporting
In addition to the required assessments listed above, additional assessments may be 
performed at the investigator’s discretion.
8.8 
Early Termination Visit
Subjects who withdraw from the study prematurely for any reason, including AEs, must 
complete an Early Termination Visit. At the time of withdrawal from the study, investigators 
should discuss treatment options with the subject and/or their parent/legal guardian to best 
manage the subject’s epilepsy. Taper of LCM may not be required for some subjects who 
discontinuestudy medication prematurely, depending on the treatment option selected by the 
investigator in consultation with the subject and/or parent/legal guardian. These subjects 
should complete the Early Termination Visit and then complete the 30-day Safety Follow-Up 
Period. 
The following assessments should be completed at the Early Termination Visit and prior to
subjects entering the blinded Taper Period (2to 4weeks).
REDACTED COPY 
assessment (for subjects with an implanted VNS device onl
REDACTED COPY 
assessment (for subjects with an implanted VNS device onl
, including orthostatic assessments)
REDACTED COPY 
, including orthostatic assessments)
ars of age
REDACTED COPY 
ars of age
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 be performed at the investigator’s discretion. The following 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 be performed at the investigator’s discretion. The following 
assessment (for subjects with an implanted VNS device onl
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
assessment (for subjects with an implanted VNS device onl
, including orthostatic assessments)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, including orthostatic assessments)
ars of age
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ars of age(onl
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(only if visit 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y if visit 
te subject diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
te subject diary on a daily
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 on a daily
te subject diary on a daily
te subject diary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
te subject diary on a daily
te subject diary
In addition to the required assessments listed above, additional assessments may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
In addition to the required assessments listed above, additional assessments may
performed at the investigator’s discretion.
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performed at the investigator’s discretion.
Earl
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Early 
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y 
Subjects who withdraw from th
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Subjects who withdraw from th
complete an Early
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complete an Early
should discuss treatment options with the subject and/or their parent/legal guardian to best 
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should discuss treatment options with the subject and/or their parent/legal guardian to best 
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manage the sub
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manage the sub
discontinue
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discontinue
investigator in consultation with the subject and/or parent/legal guardian. These subjects 
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investigator in consultation with the subject and/or parent/legal guardian. These subjects 
should complete the Early Termination Visit and 
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should complete the Early Termination Visit and 


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 58of 97
Concomitant medications
Concomitant AEDs
Changes in VNS settings
Physical examination (complete)
Tanner Stage assessment
Vital signs (BP and pulserate, including orthostatic assessments)
Body weight assessment
Height assessment
Head circumference
Neurological examination (complete)
12-lead ECG (2interpretable recordings to be performed prior to any blood draws and 
vital signs assessment and, if possible, with the subject in the supine position for 
approximately 5 minutes preceding the recordings and during the recordings)
Blood sample for clinical chemistry and hematology
Blood sample for endocrinology
Urine sample for urinalysis(for subjects ≥5 years of age)
Serum pregnancy test (for females of childbearing potential)
Blood sample for measurement of concomitant AED plasma concentrations
Blood sample for measurement of LCM plasma concentration
C-SSRS(for subjects ≥6years of age)
Clinical Global Impression of Change
Caregiver’s Global Impression of Change
Achenbach CBCL (same version used at Visit 2)
BRIEF-P/BRIEF score (version consistent with that used at Visit 2)
PedsQL score (version consistent withthat used at Visit 2)
Contact IXRS
Dispense study medication for the Taper Period (2to 4weeks)
Study medication return
Reminder to complete subject diary on a daily basis
AE reporting
Health care resource use
REDACTED COPY 
 and hematology
REDACTED COPY 
 and hematology
(for subjects 
REDACTED COPY 
(for subjects ≥5 y
REDACTED COPY 
≥5 y
 test (for females of childbearing potential)
REDACTED COPY 
 test (for females of childbearing potential)
of concomitant AED plasma concentrations
REDACTED COPY 
of concomitant AED plasma concentrations
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
interpretable recordings to be performed prior to any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
interpretable recordings to be performed prior to any blood draws and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 blood draws and 
interpretable recordings to be performed prior to any blood draws and 
interpretable recordings to be performed prior to any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
interpretable recordings to be performed prior to any blood draws and 
interpretable recordings to be performed prior to any
in the supine position for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
in the supine position for 
nd during the recordings
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nd during the recordings
≥5 y
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≥5 years of age)
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ears of age)
 test (for females of childbearing potential)
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 test (for females of childbearing potential)
of concomitant AED plasma concentrations
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
of concomitant AED plasma concentrations
Blood sample for measurement of L
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Blood sample for measurement of LCM plasma concentration
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CM plasma concentration
ye
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years of age
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ars of age
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mpression of Change
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mpression of Change
Caregiver’s Global Impression of Change
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Caregiver’s Global Impression of Change
Achenbach CBCL (
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Achenbach CBCL (same 
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same 
/BRIEF score (version consistent with
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
/BRIEF score (version consistent with
PedsQL
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PedsQL score (version consistent with
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 score (version consistent with
Contact IXRS
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Contact IXRS
Dispense study
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Dispense study

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


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 59of 97
The subject will be scheduled to return to the clinic for the Taper Visit (see Section8.5.1).
Subjects who do not taper study medication due to other treatment options should be 
scheduled for a Safety Follow-Up Visit as specified in Table 5-3. The morning of the next 
clinic visit, the subject should take concomitant AEDs and study medication, as applicable, at 
the usual time(s).
9
ASSESSMENT OF EFFICACY 
9.1
Specification of efficacy parameters
The assessment of efficacy is based on partial-onset seizure frequency.
The primary efficacy variable is the change in partial-onset seizure frequency per 28days 
from Baseline to the Maintenance Period.
The secondary efficacy variables are as follows:
Proportion of responders, where a responder is a subject experiencing a 50% or greater 
reduction in partial-onset seizure frequency from Baseline to the Maintenance Period
Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or >75% reduction in 
partial-onset seizure frequency from Baseline to the end of Maintenance Period
Change in partial-onset seizure frequency per 28days from Baseline to the entire 
treatment (ie, Titration+Maintenance Periods)
Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or >75% reduction in 
partial-onset seizure frequency from Baseline to the entire treatment (ie, 
Titration+Maintenance Periods)
Proportion of subjects experiencing no change in partial-onset seizure frequency (between 
<25%reduction and <25% increase) from Baseline to the entire treatment (ie, 
Titration+Maintenance Periods)
Proportion of subjects experiencing an increase in partial-onset seizure frequency of 
≥25% from Baseline to the entire treatment (ie, Titration+Maintenanc e Periods)
Change in partial-onset seizure frequency per 28days from Baseline to the entire 
treatment (ie, Titration+Maintenance Periods) by seizure type
Proportion of seizure-free days during the Maintenance Period for subjects who entered 
the Maintenance Period
Proportion of subjects who achieved “seizure-free” status (yes/no) for subjects who 
completed the Maintenance Period
Other efficacy variables are as follows:
Clinical Global Impression of Change at the end of the Maintenance Period
Caregiver’s Global Impression of Change at the end of the Maintenance Period
Quality of life assessments (PedsQL)
REDACTED COPY 
line to the end of Maintenance Period
REDACTED COPY 
line to the end of Maintenance Period
 per 28
REDACTED COPY 
 per 28day
REDACTED COPY 
day
treatment (ie, Titration+Maintenance Periods)
REDACTED COPY 
treatment (ie, Titration+Maintenance Periods)
≥25% to <50%, 50% to 75%, or >75% reduction in 
REDACTED COPY 
≥25% to <50%, 50% to 75%, or >75% reduction in 
 from Baseline to the entire treatment (ie, 
REDACTED COPY 
 from Baseline to the entire treatment (ie, 
Proportion of subjects experiencing no change in partial-
REDACTED COPY 
Proportion of subjects experiencing no change in partial-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 per 28
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 per 28day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
day
Proportion of responders, where a responder is a subject experiencing a 50% or greater 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of responders, where a responder is a subject experiencing a 50% or greater 
 from Baseline to the Maintenance Period
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 from Baseline to the Maintenance Period
≥25% to <50%, 50% to 75%, or >75% reduction in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
≥25% to <50%, 50% to 75%, or >75% reduction in 
line to the end of Maintenance Period
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line to the end of Maintenance Period
day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
days from Baseline to the entire 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s from Baseline to the entire 
≥25% to <50%, 50% to 75%, or >75% reduction in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
≥25% to <50%, 50% to 75%, or >75% reduction in 
 from Baseline to the entire treatment (ie, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 from Baseline to the entire treatment (ie, 
Proportion of subjects experiencing no change in partial-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of subjects experiencing no change in partial-
increase) from Baseline to the entire tre
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
increase) from Baseline to the entire tre
Titration+Maintenance Periods)
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Titration+Maintenance Periods)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of subjects experiencing an increase in partial-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of subjects experiencing an increase in partial-
from Baseline to the entire treatment (ie, Titration+Maintenance Periods)
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from Baseline to the entire treatment (ie, Titration+Maintenance Periods)
Change in partial
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Change in partial-
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-onset seizure frequency
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onset seizure frequency
treatment (ie, Titration+Maintenance Periods) b
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treatment (ie, Titration+Maintenance Periods) b
Proportion of seizure-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of seizure-
the Maintenance Period
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the Maintenance Period
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of subjects who achieved “seizure-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Proportion of subjects who achieved “seizure-
completed the Maintenance Period
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
completed the Maintenance Period
Other efficacy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Other efficacy

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


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Health care resource use (concomitant AEDs, medical procedures, health care provider 
consultations including hospitalizations not foreseen by the protocol)
9.2
Methods for assessing efficacy parameters
9.2.1
Primary and secondary efficacy parameters
Primary and secondary efficacy variables will be measured using data obtained from a 
subject diary. Subjects or parents/caregivers will keep a diary to record the daily seizure 
activity from the beginning of the Baseline Period until the last visit, recording both seizure 
type and seizure frequency. The seizure records will be checked by the investigator with 
regards to correct and thorough daily completion by the subject, and to determine if a dose 
adjustment is required. At each vi sit and telephone contact subject and/or legal representative 
should be reminded to complete the subject diaryon a daily basis.
9.2.2
Other efficacy parameters
9.2.2.1
Clinical and Caregiver’s Global Impression of Change
The Clinical Global Impression of Change is a 7-point categorical rating scale in which the 
investigator assesses the subject’s change from Baseline in clinical status, including an 
evaluation of seizure frequency and intensity, the occurrence of AEs, and subject’s functional 
status.
The Caregiver’s Global Impression of Change is a 7-point categorical rating scale in which 
the caregiver assesses the subject’s change from Baseline in clinical status, including an 
evaluation of seizure frequency and intensity, the occurrence of AEs, and subject’s functional 
status.
9.2.2.2
Healthcare resource use
For health care resource use parameters, the following will be evaluated: concomitant AEDs, 
medical procedures, health care provider consultationsincluding hospitalizations not foreseen 
by the protocol.
9.2.2.3
PedsQL
The PedsQL is a validated instrument that consists of generic core scales suitable for use with 
pediatric populations, including those with acute or chronic health conditions (Varni et al, 
2001). The PedsQL will be administered only in countries where a translated version is 
available. The version of the PedsQL used at Visit2 (Baseline) should be maintained for the 
duration of the study in accordance with the tabular schedules of study procedures 
(Section5.2).
The PedsQL Measurement Model consists of developmentally appropriate forms for pediatric 
subjects ≥2years to ≤4years, ≥5years to ≤7years, ≥8years to ≤12years, and ≥13years to 
≤18years of age. Self-report is measured for pediatric subjects ≥5years to ≤18years of age, 
and parent proxy report of child health-related quality of life (HRQoL) is measured for 
pediatric subjects ≤4 years of age.
The multidimensional PedsQL generic core scales encompass the essential core domains for 
pediatric HRQoL measurement: Physical Functioning, Emotional Functioning, Social 
REDACTED COPY 
y, the occurrence of AEs, and subject’s functional 
REDACTED COPY 
y, the occurrence of AEs, and subject’s functional 
lobal Impression of Change is a 7
REDACTED COPY 
lobal Impression of Change is a 7
the caregiver assesses the subject’s change from Baseline in clinical status, including an 
REDACTED COPY 
the caregiver assesses the subject’s change from Baseline in clinical status, including an 
 and intensit
REDACTED COPY 
 and intensity, the occurrence of AEs, and subject’s functional 
REDACTED COPY 
y, the occurrence of AEs, and subject’s functional 
Healthcare resource use
REDACTED COPY 
Healthcare resource use
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
l the last visit, recording both seizure 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
l the last visit, recording both seizure 
 the investigator with 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 the investigator with 
 the subject, and to determine if a dose 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 the subject, and to determine if a dose 
sit and telephone contact subject and/or legal representative 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sit and telephone contact subject and/or legal representative 
Global Impression of Change
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Global Impression of Change
point categorical rating scale in which the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
point categorical rating scale in which the 
investigator assesses the subject’s change from Baseline in clinical status, including an 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
investigator assesses the subject’s change from Baseline in clinical status, including an 
y, the occurrence of AEs, and subject’s functional 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y, the occurrence of AEs, and subject’s functional 
lobal Impression of Change is a 7
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
lobal Impression of Change is a 7-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-point categorical rating scale in which 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
point categorical rating scale in which 
the caregiver assesses the subject’s change from Baseline in clinical status, including an 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the caregiver assesses the subject’s change from Baseline in clinical status, including an 
y, the occurrence of AEs, and subject’s functional 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y, the occurrence of AEs, and subject’s functional 
Healthcare resource use
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Healthcare resource use
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
For health care resource use parameters, the following will be evaluated: concomitant AEDs, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
For health care resource use parameters, the following will be evaluated: concomitant AEDs, 
medical procedures, health care provider consultations
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
medical procedures, health care provider consultations
PedsQL is a validated instrument that consists of generic core scales suitable for use with 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
PedsQL is a validated instrument that consists of generic core scales suitable for use with 
pediatric populations, including those with acute or chronic health conditions (Varni et al, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
pediatric populations, including those with acute or chronic health conditions (Varni et al, 
2001). The PedsQL will be administered onl
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2001). The PedsQL will be administered onl
available. The version of the PedsQL
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
available. The version of the PedsQL
duration of the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
duration of the study
(Section
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(Section
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
5.2
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
5.2).
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
).
The PedsQL Measurement Model consists of developmentally
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The PedsQL Measurement Model consists of developmentally
subjects 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
subjects 
≤18
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
≤18


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Functioning, and School Functioning. The PedsQL assessment is retrospective to the prior 
4 weeks, and individual items are scored using a 5-point Likert scale (never, almost never, 
sometimes, often, or always). A total health summary score ranging between 0 and 100 is 
calculated from the sum of the raw scores, with higher scores indicating higher HRQoL.
10
ASSESSMENT OF PHARMACOKINETIC/ 
PHARMACODYNAMIC VARIABLE(S)
Blood samples for the determination of LCM and concomitant AED plasma concentrations 
will be collected according to the tabular schedulesof study procedures (see Section5.2). In 
each case, the time the subject took the most recent dose of study medication and the time of 
blood sampling must be recorded. Actual sampling times will be recorded in the CRF to the 
minute.
Details of plasma sample collection and processing, sample labeling, and s hipment will be 
provided in the laboratory manual.
11
ASSESSMENT OF SAFETY
11.1
Adverse events
11.1.1
Definition of adverse event
An adverse event 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 diseasetemporally associated with 
the use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.
In order to ensure complete safety data collection, all AEs occurring during the study 
(ie,after the signing of the Informed Consent form), including any pretreatment and 
posttreatment periods required by the protocol, must be reported in the CRF even if no 
investigational product 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 investigational product 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 Baseline Period.
11.1.2
Procedures for reporting and recording adverse events
The subjector subject’s parent(s)/caregiver(s)/legal representative(s)will be given the 
opportunity to report AEs spontaneously. A general prompt will also be given at each study 
visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
In addition, the investigator should review any self-assessment procedures (eg, diary cards) 
employed in the study.
REDACTED COPY 
untoward medical occurrence in a patient or clinical 
REDACTED COPY 
untoward medical occurrence in a patient or clinical 
subject administered a pharmaceutical product that does not necessarily
REDACTED COPY 
subject administered a pharmaceutical product that does not necessarily
relationship with this treatment. An AE can therefore be an
REDACTED COPY 
relationship with this treatment. An AE can therefore be an
 finding), s
REDACTED COPY 
 finding), s
the use of a medicinal (investigational) product, whether or not related to the medicinal 
REDACTED COPY 
the use of a medicinal (investigational) product, whether or not related to the medicinal 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Blood samples for the determination of LCM and concomitant AED plasma concentrations 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Blood samples for the determination of LCM and concomitant AED plasma concentrations 
5.2
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
5.2). In 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
). In 
 medication and the time of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 medication and the time of 
blood sampling must be recorded. Actual sampling times will be recorded in the CRF to the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
blood sampling must be recorded. Actual sampling times will be recorded in the CRF to the 
plasma sample collection and processing, sample labeling, and shipment will be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
plasma sample collection and processing, sample labeling, and shipment will be 
untoward medical occurrence in a patient or clinical 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
untoward medical occurrence in a patient or clinical 
subject administered a pharmaceutical product that does not necessarily
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
subject administered a pharmaceutical product that does not necessarily
relationship with this treatment. An AE can therefore be an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
relationship with this treatment. An AE can therefore be an
 finding), s
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 finding), sym
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ymptom, or disease
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ptom, or disease
the use of a medicinal (investigational) product, whether or not related to the medicinal 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the use of a medicinal (investigational) product, whether or not related to the medicinal 
 data collection, all AEs occurring during the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 data collection, all AEs occurring during the study
f the Informed Consent form), including an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
f the Informed Consent form), including an
posttreatment periods required by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
posttreatment periods required by the protocol, must be reported in the CRF even if no 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 the protocol, must be reported in the CRF even if no 
posttreatment periods required by the protocol, must be reported in the CRF even if no 
posttreatment periods required by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
posttreatment periods required by the protocol, must be reported in the CRF even if no 
posttreatment periods required by
investigational product was taken but specific study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
investigational product was taken but specific study
includes all AEs not pr
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
includes all AEs not present prior to the initial visit and all AEs that recurred or worsened 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
esent prior to the initial visit and all AEs that recurred or worsened 
ptoms of the condition/disease for which the investigational product is being 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ptoms of the condition/disease for which the investigational product is being 
studied should be recorded as AEs onl
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
studied should be recorded as AEs onl
frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
frequency or intensit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 or intensit
profile known to the investigator from the subject’s history
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
profile known to the investigator from the subject’s history
11.1.2
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
11.1.2
The su
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The su
opportunity
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opportunity


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11.1.3
Description of adverse events
When recording an AE, the investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The CRF 
and source documents should be consistent. Any discrepancies between the subject’s own 
words on his/her own records (eg, diary card) and the corresponding medical terminology 
should be clarified in the source documentation.
Details for completion of the Adverse Event CRF (including judgment of relationship to 
study drug) are described in the CRF Completion Guidelines.
11.1.4 
Follow up of adverse events
An AE should be followed until it has resolved, has a stable sequelae, the investigator 
determines that it is no longer clinically significant, or the subject is lost to follow-up. 
If an AE is still ongoing at the end of the study for a subject, follow up should beprovided 
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 30days after the subject has discontinued his/her IMP.
11.1.5
Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported 
with:
The outcome date of the first AE that is not related to the natural course of the disease 
being the same as the start date of the repeated AE, and the outcome of “worsening”
The AE verbatim term being the same for the first and repeated AE, so that the repeated 
AE canbe easily identified as the worsening of the first one
11.1.6 
Pregnancy
Should a subject become pregnant after the first intake of any IMP, UCB’s Drug Safety 
department should be informed immediately. The subject should be withdrawn from the 
study as soon as pregnancy is known, and the following should be completed:
The subject should return for an Early Termination Visit and Taper Visit.
The subject should immediately stop the intake of the IMP or be down-titrated as 
instructed at the Early Termination Visit.
A Safety Follow-Up Visit should occur 2 weeks ±2days after the subject has 
discontinued her IMP.
A Safety Follow-Up Telephone Contact should occur30 days (-1/+3days)after the 
subject has discontinued IMP.
The investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, 
UCB will ask the investigator or designee to contact the subject and his partner to request 
REDACTED COPY 
s after the subject has discontinued his/her IMP.
REDACTED COPY 
s after the subject has discontinued his/her IMP.
Rule for repetition of an adverse event
REDACTED COPY 
Rule for repetition of an adverse event
 of an AE should lead to the repetition of the AE being reported 
REDACTED COPY 
 of an AE should lead to the repetition of the AE being reported 
date of the first AE that is not related to the natural course of the disease 
REDACTED COPY 
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”
REDACTED COPY 
being the same as the start date of the repeated AE, and the outcome of “worsening”
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ld be followed until it has resolved, has a stable sequelae, the investigator 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ld be followed until it has resolved, has a stable sequelae, the investigator 
y significant, or the subject is lost to follow
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y significant, or the subject is lost to follow
y for a subject, follow up should be
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y for a subject, follow up should be
until resolution/stable level of sequelae is achieved, or until the investigator no longer deems 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
until resolution/stable level of sequelae is achieved, or until the investigator no longer deems 
lost to follow up. I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
lost to follow up. If no follow 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
f no follow 
ion. The follow 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ion. The follow up will usually
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
up will usually
s after the subject has discontinued his/her IMP.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s after the subject has discontinued his/her IMP.
Rule for repetition of an adverse event
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Rule for repetition of an adverse event
 of an AE should lead to the repetition of the AE being reported 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of an AE should lead to the repetition of the AE being reported 
date of the first AE that is not related to the natural course of the disease 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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”
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
being the same as the start date of the repeated AE, and the outcome of “worsening”
The AE verbatim term being the same for the first and repeated AE, so that the repeated 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The AE verbatim term being the same for the first and repeated AE, so that the repeated 
y identified as the worsening of the first one
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y identified as the worsening of the first one
Should a subject become pregnant after the first intake of an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Should a subject become pregnant after the first intake of an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
department should be informed immediately
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
department should be informed immediately
gnancy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
gnancy
The subject should return for an Earl
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject should return for an Earl
The subject should immediately
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject should immediately
instructed at the Early
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
instructed at the Early
A 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
A Safet
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Safet
discontinued her IMP.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
discontinued her IMP.

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


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Clinical Study Protocol
Lacosamide
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Page 63of 97
consent via the Partner Pregnancy Consent form. If the partner agrees to provide additional 
information, the Pregnancy Report and Outcome form will be forwarded to the subject’s 
partner for completion.
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. The health of the child must be  
followed for 30days after birth for any significant medical issues.
In certain circumstances, UCB may request that follow up is continued for a period longer 
than 30days.
A pregnancy becomes a serious adverse event (SAE) in the following circumstances: 
miscarriage, abortion, or anomaly/birth defect of the child. Those SAEs must be additionally 
reported using the Investigator SAE Report form.
11.1.7
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the Drug Accountability or Study Drug Dosing module of the 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).
11.1.8
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 StudyPhysician or medically qualified designee/equivalent will conduct an ongoing 
review of SAEs and perform ongoing SAE reconciliations in collaboration with the Drug 
Safety 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 
signs, laboratory, or ECG results) for which data will be periodically reviewed during the 
course of the study.
11.2
Serious adverse events
11.2.1
Definition of serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:
Death
Life-threatening
REDACTED COPY 
 Drug Dosing module of the CRF. Any
REDACTED COPY 
 Drug Dosing module of the CRF. Any
nonserious AE associated with excessive dosing must be followed as an
REDACTED COPY 
nonserious AE associated with excessive dosing must be followed as an
y considered AEs or SAEs if there are associated clinical 
REDACTED COPY 
y considered AEs or SAEs if there are associated clinical 
ptoms or if the act of taking the excess medicine itself is an AE or SAE 
REDACTED COPY 
ptoms or if the act of taking the excess medicine itself is an AE or SAE 
 signal detection
REDACTED COPY 
 signal detection
y will be reviewed periodically to detect as earl
REDACTED COPY 
y will be reviewed periodically to detect as earl
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
up is continued for a period longer 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
up is continued for a period longer 
s a serious adverse event (SAE) in the following circumstances: 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s a serious adverse event (SAE) in the following circumstances: 
/birth defect of the child. Those SAEs must be additionally
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
/birth defect of the child. Those SAEs must be additionally
Overdose of investigational medicinal product
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Overdose of investigational medicinal product
ond that prescribed in the protocol and including overdose) should be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ond that prescribed in the protocol and including overdose) should be 
 Drug Dosing module of the CRF. Any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 Drug Dosing module of the CRF. Any
nonserious AE associated with excessive dosing must be followed as an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
nonserious AE associated with excessive dosing must be followed as an
y considered AEs or SAEs if there are associated clinical 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y considered AEs or SAEs if there are associated clinical 
ptoms or if the act of taking the excess medicine itself is an AE or SAE 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ptoms or if the act of taking the excess medicine itself is an AE or SAE 
y will be reviewed periodically to detect as earl
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y will be reviewed periodically to detect as earl
MP so that investigators, clinical study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
MP so that investigators, clinical study
authorities, and IRBs/IECs will be informed appropriately
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
authorities, and IRBs/IECs will be informed appropriately
sician or medically
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sician or medically qualified designee/equivalent will conduct an ongoing 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 qualified designee/equivalent will conduct an ongoing 
sician or medically qualified designee/equivalent will conduct an ongoing 
sician or medically
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sician or medically qualified designee/equivalent will conduct an ongoing 
sician or medically
review of SAEs and perform ongoing SAE reconciliations in collaboration with the Drug 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
review of SAEs and perform ongoing SAE reconciliations in collaboration with the Drug 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
As appropriate for the stage of development and accumulated experienc
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
As appropriate for the stage of development and accumulated experienc
 qualified personnel at UCB may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 qualified personnel at UCB may
signs, laboratory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
signs, laboratory, or ECG results) for which data will be periodicall
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, or ECG results) for which data will be periodicall
course of the stud
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
course of the stud
11.2.1
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
11.2.1
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
determined. An SAE must meet 1 or more of the following criteria:


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(Life-threatening does not include a reaction that might have caused death had it occurred 
in a more severe form.)
Significant or persistent disability/incapacity
Congenital anomaly/birth defect (including that occurring in a fetus)
Important medical event that, based upon appropriate medical judgment, may jeopardize 
the patient or subject and may require medical or surgical intervention to prevent 1 of the 
other outcomes listed in the definition of serious
(Important medical events may include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse.)
Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization 
criteria. However, emergency room visits that do not result in admission to the hospital 
would not qualify for this criteria and, instead, should be evaluated for 1 of the other 
criteria in the definition of serious [eg, life-threatening adverse experience, important 
medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or 
manifested in an unusual or uncharacteristic manner] do not qualify for reporting. For 
example, if a subject has a condition recorded on his/her medical history and later has a 
preplanned surgery for this condition, it is not appropriate to record the surgery or 
hospitalization as an SAE, since there is no AE upon which to assess the serious criteria. 
Please note that, if the pre-existing condition has worsened or manifested in an unusual or 
uncharacteristic manner, this would then qualify as an AE and, if necessary, the 
seriousness of the event would need to be determined.)
11.2.2
Procedures for reporting serious adverse events
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information 
by the site (see contact information for SAE reporting listed in the Serious Adverse Event 
Reporting section at the front of the protocol). The investigator must forward to UCB (or its 
representative) a duly completed “Investigator SAE Report Form for Development Drug” 
(SAE report form) provided by UCB, even if the data are incomplete, or if it is obvious that 
more data will be needed in order to draw any conclusions. Information recorded on this form 
will be entered into the global safety database.
An Investigator SAE report form will be provided to the investigator. The Investigator SAE 
Report form must be completed in English. 
It is important for the investigator, when completing the SAE report form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This 
insight from the investigator is very important for UCB to consider in assessing the safety of 
REDACTED COPY 
 for this criteria and, instead, should be evaluated for 1 of the other 
REDACTED COPY 
 for this criteria and, instead, should be evaluated for 1 of the other 
threatening adverse experience, important 
REDACTED COPY 
threatening adverse experience, important 
alizations for reasons not associated with the occurrence of an AE [eg, preplanned 
REDACTED COPY 
alizations for reasons not associated with the occurrence of an AE [eg, preplanned 
existing condition that has not worsened or 
REDACTED COPY 
existing condition that has not worsened or 
manifested in an unusual or uncharacteristic manner] do not qualify
REDACTED COPY 
manifested in an unusual or uncharacteristic manner] do not qualify
ple, if a subject has a condition recorded on his/her medical history
REDACTED COPY 
ple, if a subject has a condition recorded on his/her medical history
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 require medical or surgical intervention to prevent 1 of the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 require medical or surgical intervention to prevent 1 of the 
 include allergic bronchospasm requiring intensive 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 include allergic bronchospasm requiring intensive 
scrasias that do not result in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
scrasias that do not result in 
 or drug abuse.)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 or drug abuse.)
she is released on the same day
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
she is released on the same day
 room visit that results in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 room visit that results in 
 for the initial inpatient hospitalization 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 for the initial inpatient hospitalization 
visits that do not result in admission to the hospital 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
visits that do not result in admission to the hospital 
 for this criteria and, instead, should be evaluated for 1 of the other 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 for this criteria and, instead, should be evaluated for 1 of the other 
threatening adverse experience, important 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
threatening adverse experience, important 
alizations for reasons not associated with the occurrence of an AE [eg, preplanned 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
alizations for reasons not associated with the occurrence of an AE [eg, preplanned 
existing condition that has not worsened or 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
existing condition that has not worsened or 
manifested in an unusual or uncharacteristic manner] do not qualify
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
manifested in an unusual or uncharacteristic manner] do not qualify
ple, if a subject has a condition recorded on his/her medical history
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ple, if a subject has a condition recorded on his/her medical history
 for this condition, it is not appropriate to record the surgery
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 for this condition, it is not appropriate to record the surgery
hospitalization as an SAE, since there is no AE upon which to assess the serious cri
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
hospitalization as an SAE, since there is no AE upon which to assess the serious cri
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Please note that, if the pre-existing condition has worsened or manifested in an unusual or 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Please note that, if the pre-existing condition has worsened or manifested in an unusual or 
uncharacteristic manner, this would then qualify
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
uncharacteristic manner, this would then qualify
seriousness of the event would need to be determined.)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
seriousness of the event would need to be determined.)
Procedures for report
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Procedures for report
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information 
 the site (see contact information for SAE reporting listed in the Serious Adverse Event 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 the site (see contact information for SAE reporting listed in the Serious Adverse Event 
Reporting section at the front of the protocol)
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Reporting section at the front of the protocol)
representative) a duly
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
representative) a duly
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(SAE report form) provided by UCB, even if the data are incomplete, or if it is obvious that 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(SAE report form) provided by UCB, even if the data are incomplete, or if it is obvious that 
more data will be needed in ord
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
more data will be needed in ord
will be entered into the global safet
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be entered into the global safet
An Investigator SAE report form will be provided to the investigator. The Investigator SAE 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
An Investigator SAE report form will be provided to the investigator. The Investigator SAE 


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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 30days from the end of the study for each subject, and to also inform participating 
subjects of the need to inform the investigator of any SAE within this period. Serious AEs 
that the investigator thinks may be associated with the IMP must be reported to UCB 
regardless of the time between the event and the end of the study.
Upon receipt of the SAE report form, UCB will perform an assessment of expectedness of the 
reported SAE. The assessment of the expectedness of the SAE is based on the Investigator’s 
Brochure.
11.2.3 
Follow up of serious adverse events
An SAE should be followed until it has resolved, has a stable sequelae, the investigator 
determines that it is no longer clinically significant, or the subject is lost to follow up. 
Information on SAEs obtained after clinical database lock will be captured through the Drug 
Safety database without limitation of time.
11.3
Adverse events of special interest
An AE of special interest is any AE that a regulatory authority has mandated be reported on 
an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to 
the administration of a UCB product/compound.
The following are AEs of special interest:
The following arrhythmias: atrial fibrillation/flutter, ventricular tachycardia or fibrillation, 
AV block (2nd degree Type I and II and 3rd degree), and marked bradycardia (<45bpm)
Syncope or loss of consciousness (other than seizure related)
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 United States 
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.
REDACTED COPY 
An SAE should be followed until it has resolved, has a stable sequelae, the investig
REDACTED COPY 
An SAE should be followed until it has resolved, has a stable sequelae, the investig
determines that it is no longer clinically significant, or the subject is lost to follow up. 
REDACTED COPY 
determines that it is no longer clinically significant, or the subject is lost to follow up. 
formation on SAEs obtained after clinical database lock will be captured through the Drug 
REDACTED COPY 
formation on SAEs obtained after clinical database lock will be captured through the Drug 
 database without limitation of time.
REDACTED COPY 
 database without limitation of time.
verse events of special interest
REDACTED COPY 
verse events of special interest
 AE that a regulatory
REDACTED COPY 
 AE that a regulatory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 requested to collect and report to UCB (or its representative) 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 requested to collect and report to UCB (or its representative) 
 associated with the IMP), 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 associated with the IMP), 
 for each subject, and to also inform participating 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 for each subject, and to also inform participating 
 SAE within this period. Serious AEs 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 SAE within this period. Serious AEs 
MP must be reported to UCB 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
MP must be reported to UCB 
Upon receipt of the SAE report form, UCB will perform an assessment of expectedness of the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
reported SAE. The assessment of the expectedness of the SAE is based on the Investigator’s 
An SAE should be followed until it has resolved, has a stable sequelae, the investig
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
An SAE should be followed until it has resolved, has a stable sequelae, the investig
determines that it is no longer clinically significant, or the subject is lost to follow up. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
determines that it is no longer clinically significant, or the subject is lost to follow up. 
formation on SAEs obtained after clinical database lock will be captured through the Drug 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
formation on SAEs obtained after clinical database lock will be captured through the Drug 
verse events of special interest
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
verse events of special interest
 AE that a regulatory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 AE that a regulatory
an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to 
the administration of a UCB product/compound.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the administration of a UCB product/compound.
ng are AEs of special interest:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ng are AEs of special interest:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
yt
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ythmias: atrial fibrillation/flutter, ventricular tachy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
hmias: atrial fibrillation/flutter, ventricular tachy
AV block (2nd degree Ty
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
AV block (2nd degree Ty
ncope or loss of consciousness (other tha
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ncope or loss of consciousness (other tha
Serious suspected multiorgan h
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Serious suspected multiorgan h
Serious suspected multiorgan h
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Serious suspected multiorgan h
sponsor by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sponsor by
Food and Drug Administration:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Food and Drug Administration:
An AE or laboratory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
An AE or laboratory


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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
11.4
Immediate reporting of adverse events
The following AEs must be reported immediately:
SAE: AE that the investigator classifies as serious by the above definitions regardless of 
causality
Suspected transmission of an infectious agent via a medicinal product
AE of special interest (see Section11.3)
11.5
Anticipated serious adverse events
The following list of Anticipated SAEs has been identified, as these events are anticipated to 
occur in the population studied in this protocol at some frequency that is independent of drug 
exposure. This original list will remain in effect for the duration of the protocol (Table 11-1).
This list does not change the investigator’s obligation to report allSAEs (including 
Anticipated SAEs) as detailed in Section11.2.2.
REDACTED COPY 
ticipated serious adverse events
REDACTED COPY 
ticipated serious adverse events
The following list of Anticipated SAEs has been identified, as these events are anticipated to 
REDACTED COPY 
The following list of Anticipated SAEs has been identified, as these events are anticipated to 
occur in the population studied in this protocol at some frequency
REDACTED COPY 
occur in the population studied in this protocol at some frequency
t will remain in effect for the duration of the protocol (
REDACTED COPY 
t will remain in effect for the duration of the protocol (
This list does not change the investigator’s obligation to report 
REDACTED COPY 
This list does not change the investigator’s obligation to report 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ove definitions regardless of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ove definitions regardless of 
Suspected transmission of an infectious agent via a medicinal product
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Suspected transmission of an infectious agent via a medicinal product
ticipated serious adverse events
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ticipated serious adverse events
The following list of Anticipated SAEs has been identified, as these events are anticipated to 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The following list of Anticipated SAEs has been identified, as these events are anticipated to 
occur in the population studied in this protocol at some frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
occur in the population studied in this protocol at some frequency
t will remain in effect for the duration of the protocol (
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
t will remain in effect for the duration of the protocol (
This list does not change the investigator’s obligation to report 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This list does not change the investigator’s obligation to report 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Anticipated SAEs) as detailed in Section
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Anticipated SAEs) as detailed in Section11.2.2
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
11.2.2


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Table11-1 Anticipated SAEs for the pediatric epilepsy population
MedDRA SOC
MedDRA PT
Congenital, familial and genetic disorders
Teratogenicity
General disorders and administration site 
conditions
Sudden unexplained death in epilepsy
Nervous system disorders
Convulsion
Incontinence
Status epilepticus
Pregnancy, puerperium and perinatal disorders 
Abortion spontaneous
Psychiatric disorders
Psychotic behaviour
Abnormal behaviour
Anxiety
Sleep disorder
Reproductive system and breast disorders 
Menstrual disorder
MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; SOC=system organ class; 
SAE=serious adverse event
11.6
Laboratory measurements
Blood and urine specimens for routine assay of hematology, clinical chemistry, 
endocrinology and urinalysis testing (for subjects ≥5years of age) will be collected according 
to the tabular schedulesof study procedures, Section5.2. Urine assessments will be based on 
the subject’s ability to void and the staff’s ability to collect urine (in an appropriate 
container). A central laboratory will perform the routine analysis of blood and urine 
specimens. Pregnancytesting (for female subjects of childbearing potential) will also be 
performed (see Section11.1.6). The procedures for handling and shipping these specimens 
will be provided to the sites.
The laboratory tests to be performed are presented in Table 11-2.
REDACTED COPY 
MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; SOC=system organ 
REDACTED COPY 
MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; SOC=system organ 
REDACTED COPY 
 measurements
REDACTED COPY 
 measurements
Blood and urine specimens for routine assay
REDACTED COPY 
Blood and urine specimens for routine assay of hematology
REDACTED COPY 
 of hematology
Blood and urine specimens for routine assay of hematology
Blood and urine specimens for routine assay
REDACTED COPY 
Blood and urine specimens for routine assay of hematology
Blood and urine specimens for routine assay
(for subjects 
REDACTED COPY 
(for subjects 
 procedures, Section
REDACTED COPY 
 procedures, Section
 to void and the staff’s ability
REDACTED COPY 
 to void and the staff’s ability
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Abnormal behaviour
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Abnormal behaviour
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Sleep disorder
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Sleep disorder
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Menstrual disorder
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Menstrual disorder
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; SOC=system organ 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; SOC=system organ 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of hematology
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of hematology
(for subjects 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(for subjects 
 procedures, Section
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 procedures, Section
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 to void and the staff’s ability
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 to void and the staff’s ability
 will perform the routine anal
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 will perform the routine anal
testing (for female subjects of childbearing potential) will al
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
testing (for female subjects of childbearing potential) will al
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
11.1.6
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
11.1.6). The procedures for handling and shipping these specimens 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
). The procedures for handling and shipping these specimens 
will be provided to the sites.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be provided to the sites.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 tests to be performed are presented in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 tests to be performed are presented in 


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Table11-2 Laboratory measurements
Hematology
Clinical chemistry
Endocrinology 
Urinalysisa
Hematocrit
Calcium
FSH
pH
Hemoglobin
Phosphorus
LH
Ketones
Platelet count
Serum electrolytes (sodium, 
potassium, chloride, bicarbonate)
Testosterone
Glucose
RBC count
Creatinine
TSH
Albumin
WBC count
BUN
T3 (total and 
serum-free)
Specific gravity
Differential count
AST
T4 (total and 
serum-free)
Microscopic exam for 
blood cells or casts/hpf
ALT
T3 (total and 
serum-free)
Total bilirubin
T4 (total and 
serum-free)
Alkaline phosphatase
GGT
Glucose
Albumin
Total serum protein
Uric acid
Total cholesterol
Triglycerides
ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; 
FSH=follicle-stimulating hormone; GGT=gamma glutamyl transferase; hpf=high power field; LH=luteinizing 
hormone; RBC=red blood cells; T
3=triiodothyronine; T4=thyroxine; TSH=thyroid stimulating hormone; 
WBC=white blood cells
aUrinalysis will be performed for subjects ≥5 years of age only.
11.7
Liver function tests
Refer to Section6.3for LFT withdrawal criteria.
Transaminases (AST, ALT, or both) ≥3×ULN but <5×ULN, in the presence of total bilirubin 
≥2×ULN, or transaminases (AST, ALT, or both) ≥5×ULN will result in immediate 
discontinuation of study medication and withdrawal of the subject from the study. The LFTs 
will be repeated as soon as possible, and in no case more than 1week 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. 
In all cases of transaminases (AST, ALT, or both) ≥3xULN, testing for hepatitis A, B, and C 
will be done.
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Specific gravity
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Specific gravity
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Microscopic exam for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Microscopic exam for 
blood cells or casts/hpf
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
blood cells or casts/hpf
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; 
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ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; 
stimulating hormone; GGT=gamma glutamyl transferase; hpf=high pow
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stimulating hormone; GGT=gamma glutamyl transferase; hpf=high pow
=triiodothyronine; T
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=triiodothyronine; T
Urinalysis will be performed f
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Urinalysis will be performed for subjects 
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or subjects 
Urinalysis will be performed for subjects 
Urinalysis will be performed f
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Urinalysis will be performed for subjects 
Urinalysis will be performed f
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Liver function tests
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Liver function tests
6.3
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6.3for LFT withdrawal criteria.
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for LFT withdrawal criteria.
Transaminases (AST, ALT, or both) ≥3×ULN but <5×ULN, in the presence of total bilirubin 
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Transaminases (AST, ALT, or both) ≥3×ULN but <5×ULN, in the presence of total bilirubin 
≥2×ULN, or transaminases (AST, ALT, or both) ≥5×ULN will result in immedia
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≥2×ULN, or transaminases (AST, ALT, or both) ≥5×ULN will result in immedia
discontinuation of study
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discontinuation of study
will be repeated as soon as possible, and in no case more than 1
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will be repeated as soon as possible, and in no case more than 1
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Transaminases (AST, ALT, or both) 
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Transaminases (AST, ALT, or both) 
b
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bilirubin, will be repeated within a few day
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ilirubin, will be repeated within a few day
(ie, transaminases are 
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(ie, transaminases are 


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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.
11.8
Pregnancy testing
Females of childbearing potential will have serum and urine pregnancy tests performed 
during the study according to the tabular schedulesof study assessments (Section5.2).
11.9
Other safety measurements
11.9.1
Physical examination
Physical examinations will be performed according to the tabular schedulesof study 
procedures (Section5.2) by a medically qualified clinician licensed to perform the 
examination.
Subsequent to Visit 1, clinically significant physical examination findings should  be reported 
as AEs.
11.9.1.1
Complete physical examination
The complete physical examination will include cardiac and respiratory function via 
auscultation, temperature, and review of all body systems.Genitourinary and breast 
examinations will not be performed.
11.9.1.2
Brief physical examination
The brief physical examination will include review of the following body systems: 
Cardiovascular
Pulmonary
Abdominal (hepato-gastrointestinal)
Dermatologic
11.9.2
Neurological examination
Neurological examinations will be performed according to the tabular schedulesof study 
procedures (Section5.2) by a medically qualified clinician with documented training in the 
conduct of neurological examinations. If possible, the same clinician should conduct all 
neurological examinations for the same subject during the study. The investigator or 
subinvestigator is responsible for confirming the diagnosis of partial-onset seizures.
11.9.2.1 
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.
REDACTED COPY 
ical examination will include cardiac and respiratory function via 
REDACTED COPY 
ical examination will include cardiac and respiratory function via 
ys
REDACTED COPY 
ystems.
REDACTED COPY 
tems.
sical examination
REDACTED COPY 
sical examination
ical examination will include review of the following body
REDACTED COPY 
ical examination will include review of the following body
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of study
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of study
to perform the 
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to perform the 
1, clinically significant physical examination findings should be reported 
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1, clinically significant physical examination findings should be reported 
ical examination will include cardiac and respiratory function via 
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ical examination will include cardiac and respiratory function via 
tems.
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tems.Genitourinary
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Genitourinary
ical examination will include review of the following body
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ical examination will include review of the following body
gastrointestinal)
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gastrointestinal)
Neurological examination
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Neurological examination
Neurological examinations will be performed according to the tabular schedule
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Neurological examinations will be performed according to the tabular schedule
procedures (Section
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procedures (Section5.2
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5.2
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conduct of neurological examinations. I
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conduct of neurological examinations. I
neurological examinations for the same subject during the stud
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neurological examinations for the same subject during the stud
subinvestigator is responsible for confirming the diagnosis of partial
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subinvestigator is responsible for confirming the diagnosis of partial
11.9.2.1 
Complete neurological examination
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11.9.2.1 
Complete neurological examination
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The complete neurological examination will include selected assessment of: general 
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The complete neurological examination will include selected assessment of: general 
neurological status (level of conscio
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neurological status (level of conscio


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11.9.2.2 
Brief neurological examination
The brief neurological examination will include selected assessment of: general neurological 
status, reflexes, muscle strength, and coordination/cerebellar function.
11.9.3 
Vital signs, body weight, and height
Noninvasive BP (systolic and diastolic) and pulse rate will be measured at clinic visits after at 
least 3 minutes at rest in a supine position, according to the tabular  schedules of study 
procedures (Section5.2). Assessment of orthostatic changes will be as follows: After the 
3-minute measurement in supine position, the subject is asked to stand up, and BP and pulse 
rate are taken approximately 1 minute and approximately 3 minutes after the subject stands 
up, as feasible.
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 
schedules of study procedures (Section5.2).
11.9.4
12-lead ECG
Standard 12-lead ECGs (2 interpretable recordings) will be performed according to the 
tabular schedules of study assessments (Section5.2).Care should be taken to ensure proper 
lead placement and quality ECG recordings. The ECGs will be performed prior to any blood 
draws and vital signs assessment. The subjects should rest in the supine position for 
approximately 5 minutes beforethe ECG recordingand during the recording. The recordings 
should be made 20 to 30 minutes apart.
11.9.5
Overall ECG interpretation
Electrocardiograms will be reviewed locally by the investigator, subinvestigator, or qualified 
designated reader and at a central ECG laboratory. If the reading identifies second-or 
third-degree AV block or another abnormal ECG finding that is assessed by the investigator 
to be clinically significant, then the ECG should be repeated on the same day. If the clinically 
significant abnormality is confirmed by the repeat ECG, then the subject must be withdrawn 
from the study (see Section6.3). 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 the study.
11.9.6 
Tanner Stage
The investigator or qualified designee will evaluate the subject’s sexual development using 
the 3-item Tanner scale, according to the tabular schedules of study procedures (Section5.2). 
The investigator should use clinical judgment in deciding which subjects are selected for 
evaluation of Tanner Stage (ie, those subjects who are pubescent at Visit 1 or who will enter 
puberty during the course of the study).
11.9.7
Achenbach CBCL
The Achenbach CBCL is a widely used validated questionnaire to evaluate a child’s 
competencies and behavioral/emotional problems. Behavioral problems will be scored by the 
REDACTED COPY 
Care should be taken to ensure proper 
REDACTED COPY 
Care should be taken to ensure proper 
 ECG recordings. The ECGs will be performed prior to an
REDACTED COPY 
 ECG recordings. The ECGs will be performed prior to an
The subjects should rest in the supine position for 
REDACTED COPY 
The subjects should rest in the supine position for 
the ECG recording
REDACTED COPY 
the ECG recording
Overall ECG interpretation
REDACTED COPY 
Overall ECG interpretation
Electrocardiograms will be reviewed locall
REDACTED COPY 
Electrocardiograms will be reviewed locall
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minute measurement in supine position, the subject is asked to stand up, and BP and pulse 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
minute measurement in supine position, the subject is asked to stand up, and BP and pulse 
 3 minutes after the subject stands 
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 3 minutes after the subject stands 
d without shoes and wearing light clothing, and height will be 
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d without shoes and wearing light clothing, and height will be 
 weight and height will be assessed according to the tabular 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 weight and height will be assessed according to the tabular 
will be performed according to the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be performed according to the 
Care should be taken to ensure proper 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Care should be taken to ensure proper 
 ECG recordings. The ECGs will be performed prior to an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 ECG recordings. The ECGs will be performed prior to an
The subjects should rest in the supine position for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subjects should rest in the supine position for 
the ECG recording
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the ECG recordingand 
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and during the recording. The recordings 
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during the recording. The recordings 
Overall ECG interpretation
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Overall ECG interpretation
Electrocardiograms will be reviewed locall
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Electrocardiograms will be reviewed locally b
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y b
designated reader and at a central ECG laboratory. If the reading identifies second
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
designated reader and at a central ECG laboratory. If the reading identifies second
-degree AV block or another abnormal ECG finding that is assessed by the investigator 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-degree AV block or another abnormal ECG finding that is assessed by the investigator 
 significant, then the ECG should be repeated on th
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 significant, then the ECG should be repeated on th
 is confirmed by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 is confirmed by
 (see Section
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 (see Section6.3
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6.3
central ECG laboratory to confirm the presence of a clinically
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central ECG laboratory to confirm the presence of a clinically
It remains the responsibility
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
It remains the responsibility
ignificance on the basis of the complete clinical picture and whether this finding 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ignificance on the basis of the complete clinical picture and whether this finding 
influences the subject’s participation in the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
influences the subject’s participation in the study
he investigator or qualified designee will evaluate the subject’s sexual development using 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
he investigator or qualified designee will evaluate the subject’s sexual development using 
the 3
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the 3-
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-item 
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item 
The investigator should use clinical judgment in deciding which subje
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The investigator should use clinical judgment in deciding which subje
evaluation of Tanner Stage (ie, those subjects who are pubescent at Visit
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evaluation of Tanner Stage (ie, those subjects who are pubescent at Visit


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parent(s)/legal representative(s). Depending on the subject’s age, 2versions of the CBCL will 
be used. The CBCL/1½-5 checklist is intended for use in children 18monthsto 5years and 
11 months of age. For subjects ≥6years to <17years of ageat Screening, the CBCL/6-18 
version will be used.The Achenbach CBCL will only be administered in countries where a 
translated version is available.
For each subject, the same version of the scale that is completed at Visit 2 (Baseline) should 
be maintained for the duration of the study in accordance with the tabular schedules of study 
procedures (Section5.2) and shouldbe completed by the same parent/legal representative.
The completion of the Achenbach CBCL will require approximately 45minutes. 
In both questionnaires, the occurrence of certain problems and behaviors in the past 6months 
will be scored on the following scale:
0=not true (as far as known)
1=somewhat or sometimes true
2=very true or often true
Eight syndrome scores will be calculated from these questions, which will in turn be 
summarized by 2composite scores. Additionally, for each score on the question, syndrome, 
and total level, categorizations based on a normative sample will be used to evaluate normal, 
borderline, or clinically relevant behavior.
In addition, the Achenbach CBCL/6-18 includes ratings related to performance in school, 
activities in leisure time, and special interests.
11.9.8
Assessment of suicidality
Suicidality will be assessed by trained study personnel using the C-SSRS (Columbia 
University Medical Center, 2008). 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 schedules of study procedures (Section5.2). All subjects 
who are ≥6years of age will complete the “Baseline/Screening” version of the C-SSRS at 
Visit 1and will complete the “Since Last Visit” version at subsequent visits. If a subject 
becomes 6years 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 <6years 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 6years 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.
REDACTED COPY 
, for each score on the question, sy
REDACTED COPY 
, for each score on the question, sy
and total level, categorizations based on a normative sample will be used to evaluate normal, 
REDACTED COPY 
and total level, categorizations based on a normative sample will be used to evaluate normal, 
-18 includes ratings related to performance in school, 
REDACTED COPY 
-18 includes ratings related to performance in school, 
activities in leisure time, and special interests.
REDACTED COPY 
activities in leisure time, and special interests.
sessment of suicidality
REDACTED COPY 
sessment of suicidality
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 in accordance with the tabular schedules of study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 in accordance with the tabular schedules of study
same parent/legal representative
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same parent/legal representative.
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.
n problems and behaviors in the past 6
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
n problems and behaviors in the past 6months 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
months 
yndrome scores will be calculated from these questions, which will in turn be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
yndrome scores will be calculated from these questions, which will in turn be 
, for each score on the question, sy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, for each score on the question, sy
and total level, categorizations based on a normative sample will be used to evaluate normal, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
and total level, categorizations based on a normative sample will be used to evaluate normal, 
-18 includes ratings related to performance in school, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-18 includes ratings related to performance in school, 
activities in leisure time, and special interests.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
activities in leisure time, and special interests.
sessment of suicidality
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sessment of suicidality
 trained study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 trained study
 Medical Center, 2008). T
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 Medical Center, 2008). This scale will be used for Screening as well as to assess 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
his scale will be used for Screening as well as to assess 
suicidal ideation and behavior that may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
suicidal ideation and behavior that may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
completed according to the tabular schedules of study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
completed according to the tabular schedules of study
will complete the 
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will complete the 
will complete
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will completethe “
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the “
ars of age during the study, the "Already Enrolled" version of the C
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ars of age during the study, the "Already Enrolled" version of the C
at the first visit at which the subject is 6 y
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at the first visit at which the subject is 6 y
Visit” version at subsequent visits.
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Visit” version at subsequent visits.
SSRS is not validate
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SSRS is not validate
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population. Subjects should be monitored for an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
population. Subjects should be monitored for an
warning signs of depression. The investigator should be aware of common warning signs that 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
warning signs of depression. The investigator should be aware of common warning signs that 
might be a 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
might be a 
children 
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children 
Diagnostic and Statistical Manual of Mental Disorders. Parents and caregivers should also be
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Diagnostic and Statistical Manual of Mental Disorders. Parents and caregivers should also be


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11.9.9
BRIEF-P and BRIEF
The BRIEF-P and the BRIEF are validated tools that will be used for the evaluation of 
subjects ≥2 years to <5 years of age and≥5 years of age, respectively. The BRIEF-P and 
BRIEF will be used only in countries where a translated scale is available. For each subject,
the same version (BRIEF-P or BRIEF) that isusedat Visit 2 (Baseline) should be maintained 
for the duration of the study in accordance with the tabular schedules of study procedures 
(Section5.2).
The BRIEF-P and BRIEF include rating forms used by parents to assess subjects’ executive 
functioning.Executive functions broadly encompass a set of cognitive skills that are 
responsible for the planning, initiation, sequencing, and monitoring of complex goal-directed 
behavior.
The BRIEF-P rating form consists of itemsthat measure various aspects of executive 
functioning: Inhibit, Shift, Emotional Control, Working Memory, and Plan/Organize. The 
clinical scales form 3broad indexes (Inhibitory Self-Control, Flexibility, and Emergent 
Metacognition) and 1 composite score (Global Executive Composite).
The BRIEF rating form contains items in nonoverlapping clinical scales. These theoretically 
and statistically derived scales form 2 broader Indexes: Behavioral Regulation (3 scales) and 
Metacognition (5 scales), as well as a Global Executive Composite score.
Both the BRIEF-P and the BRIEF include validity scales to measure negativity and 
inconsistency of responses. 
12
STUDY MANAGEMENT ANDADMINISTRATION 
12.1
Adherence to protocol
The investigator should not deviate from the protocol. However, the investigator should take 
any measure necessary in deviation from or not defined by the protocol in order to protect 
clinical study subjects from any immediate hazard to their health and safety. In this case, this 
action should be taken immediately, without prior notification of the regulatory authority, 
IRB/IEC, or sponsor.
After implementation of such measure, the investigator must notify the Clinical Project 
Managerof the sponsor within 24 hours and follow any local regulatory requirements.
12.2
Monitoring
UCB (or designee) will monitor the study to meet the sponsor’s monitoring Standard 
Operating Procedures (SOPs), ICH-GCP guideline, and applicable regulatory requirements, 
and to ensure that study initiation, conduct, and closure are adequate. Monitoring of the study 
may be delegated by UCB to a contract research organization (CRO) or a contract monitor.
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).
REDACTED COPY 
 derived scales form 2 broader Indexes: Behavioral Regulation (3 scales) and 
REDACTED COPY 
 derived scales form 2 broader Indexes: Behavioral Regulation (3 scales) and 
lobal Executive Composite score.
REDACTED COPY 
lobal Executive Composite score.
P and the BRIEF include validity scales to measure negativity
REDACTED COPY 
P and the BRIEF include validity scales to measure negativity
EMENT A
REDACTED COPY 
EMENT A
herence to protocol
REDACTED COPY 
herence to protocol
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ess subjects’ executive 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ess subjects’ executive 
responsible for the planning, initiation, sequencing, and monitoring of complex goal
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
responsible for the planning, initiation, sequencing, and monitoring of complex goal-directed 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-directed 
that measure various aspects of executive 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
that measure various aspects of executive 
, and Plan/Organize. The 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, and Plan/Organize. The 
Control, Flexibility
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Control, Flexibility, and Emergent 
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, and Emergent 
composite score (Global Executive Composite).
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
composite score (Global Executive Composite).
The BRIEF rating form contains items in nonoverlapping clinical scales. These theoretically
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The BRIEF rating form contains items in nonoverlapping clinical scales. These theoretically
 derived scales form 2 broader Indexes: Behavioral Regulation (3 scales) and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 derived scales form 2 broader Indexes: Behavioral Regulation (3 scales) and 
lobal Executive Composite score.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
lobal Executive Composite score.
P and the BRIEF include validity scales to measure negativity
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
P and the BRIEF include validity scales to measure negativity
EMENT A
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EMENT AND
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ND
herence to protocol
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herence to protocol
The investigator should not deviate from the protocol.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The investigator should not deviate from the protocol.
 in deviation from or not defined by
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 in deviation from or not defined by
 subjects from any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 subjects from any immediate hazard to their health and safety
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 immediate hazard to their health and safety
 subjects from any immediate hazard to their health and safety
 subjects from any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 subjects from any immediate hazard to their health and safety
 subjects from any
immediately
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
immediately
After implementation of such measure, the investigator must notify
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
After implementation of such measure, the investigator must notify
of the sponsor within 24 hours and follow any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
of the sponsor within 24 hours and follow any
Monitoring
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Monitoring
UCB (or designee) will monitor the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
UCB (or designee) will monitor the study
Operating Procedures (SOPs), I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Operating Procedures (SOPs), I
and to ensure that stud
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
and to ensure that stud
may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
may be delegated by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 be delegated by
may be delegated by
may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
may be delegated by
may
The investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 73of 97
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.
12.2.1
Definition of source data 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies of CRFs 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.
Electronic data records, such as Holter monitor records or EEG records, must be saved and 
stored as instructed by UCB (or designee).
12.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During 
monitoring visits, reported data are reviewed with regard to being accurate, complete, and 
verifiable from source documents (eg, subject files, recordings from automated instruments, 
tracings [ECG], x-ray films, laboratory notes). All data reported on the CRF should be 
supported by source documents, unless otherwise specified in Section 12.2.1.
12.3
Data handling
12.3.1
Case Report form completion
Thisstudy 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.
Any change or correction to the electronic Case Report form (eCRF) after saving must be 
accompanied by a reason for the change.
Corrections made after the investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the investigator.
REDACTED COPY 
Source documents that are computer generated and stored electronicall
REDACTED COPY 
Source documents that are computer generated and stored electronicall
y the monitor (eg, ECG reports). Once printed, these copies should be signed and 
REDACTED COPY 
y the monitor (eg, ECG reports). Once printed, these copies should be signed and 
y the investigator and become a permanent part of the sub
REDACTED COPY 
y the investigator and become a permanent part of the sub
The investigator will facilitate the process for enabling the monitor to compare the content of 
REDACTED COPY 
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.
REDACTED COPY 
the printout and the data stored in the computer to ensure all data are consistent.
Electronic data records, such as Holter monitor rec
REDACTED COPY 
Electronic data records, such as Holter monitor rec
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
ping, printing, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ping, printing, 
 attachments 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 attachments 
-stick notes). Photocopies of CRFs are not considered acceptable 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-stick notes). Photocopies of CRFs are not considered acceptable 
Source documents are original records in which raw data are first recorded. These may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Source documents are original records in which raw data are first recorded. These may
l practitioner records, charts, diaries, x-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
l practitioner records, charts, diaries, x-ray
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rays, laboratory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s, laboratory
 records, care records, ECG or other printouts, completed scales, or 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 records, care records, ECG or other printouts, completed scales, or 
 of life questionnaires, for example. Source documents should be kept in a secure, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of life questionnaires, for example. Source documents should be kept in a secure, 
Source documents that are computer generated and stored electronicall
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Source documents that are computer generated and stored electronicall
y the monitor (eg, ECG reports). Once printed, these copies should be signed and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y the monitor (eg, ECG reports). Once printed, these copies should be signed and 
y the investigator and become a permanent part of the sub
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y the investigator and become a permanent part of the sub
The investigator will facilitate the process for enabling the monitor to compare the content of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the printout and the data stored in the computer to ensure all data are consistent.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Electronic data records, such as Holter monitor rec
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Electronic data records, such as Holter monitor rec
y UCB (or designee).
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y UCB (or designee).
Source data verification
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Source data verification
Source data verification ensures accuracy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Source data verification ensures accuracy
monitoring visits, reported data are reviewed with regard to being accurate, complete, and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
monitoring visits, reported data are reviewed with regard to being accurate, complete, and 
verifiable from source documents (eg, subject files, recordings from automated
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
verifiable from source documents (eg, subject files, recordings from automated
ray
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ray films, laboratory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 films, laboratory
ray films, laboratory
ray
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ray films, laboratory
ray
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 source documents, unless otherwise specified in Section 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 source documents, unless otherwise specified in Section 
Data handling
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Data handling
study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
study is performed 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 is performed 
study is performed 
study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
study is performed 
study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
prompt reporting of accurate, complete, and legible data in the electronic CRFs and in all 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
prompt reporting of accurate, complete, and legible data in the electronic CRFs and in all 
required reports.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
required reports.
Any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Any


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 74of 97
The investigator should maintain a list of personnel authorized to enter data into the eCRF.
Detailed instructions will be provided in the eCRF Completion Guidelines.
12.3.2 
Database entry and reconciliation
Case Report forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning 
checks will be used in addition to manual review to check for discrepancies and to ensure 
consistency of the data. Thisstudy is performed using RDC; the data are entered into the 
eCRFs once and are subsequently verified.
An electronic audit trail system will be maintained within the CDMS to track all data changes 
in the database once the data have been saved initially into the system or electronically 
loaded. Regular backups of the electronic data will be performed.
12.3.3
Subject Screening and Enrollment log/Subject Identification Code 
list
The subject’s screening and enrollment will be recorded in the Subject Screening and 
Enrollment Log.
The investigator will keep a Subject Identification Code list. This list remains with the 
investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
12.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at 
a single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, 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 study drug and other material in accordance with UCB procedures for the study.
12.5
Archiving and data retention
The investigator will maintain adequate records for the study, including 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 2years 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 2years have elapsed since 
REDACTED COPY 
The investigator will keep a Subject Identification Code list. This list remains with the 
REDACTED COPY 
The investigator will keep a Subject Identification Code list. This list remains with the 
investigator and is used for unambiguous identification of each subject.
REDACTED COPY 
investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be
REDACTED COPY 
The subject’s consent and enrollment in the study must be
 the study
REDACTED COPY 
 the study and document the dates of the subject’s 
REDACTED COPY 
 and document the dates of the subject’s 
 the study and document the dates of the subject’s 
 the study
REDACTED COPY 
 the study and document the dates of the subject’s 
 the study
Termination of the study
REDACTED COPY 
Termination of the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
An electronic audit trail system will be maintained within the CDMS to track all data changes 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
An electronic audit trail system will be maintained within the CDMS to track all data changes 
stem or electronicall
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
stem or electronicall
Subject Screening and Enrollment log/Subject Identification Code 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject Screening and Enrollment log/Subject Identification Code 
The subject’s screening and enrollment will be recorded in the Su
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject’s screening and enrollment will be recorded in the Subject Screening and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
bject Screening and 
The subject’s screening and enrollment will be recorded in the Subject Screening and 
The subject’s screening and enrollment will be recorded in the Su
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject’s screening and enrollment will be recorded in the Subject Screening and 
The subject’s screening and enrollment will be recorded in the Su
The investigator will keep a Subject Identification Code list. This list remains with the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The investigator will keep a Subject Identification Code list. This list remains with the 
investigator and is used for unambiguous identification of each subject.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
investigator and is used for unambiguous identification of each subject.
The subject’s consent and enrollment in the study must be
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The subject’s consent and enrollment in the study must be
 and document the dates of the subject’s 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 and document the dates of the subject’s 
Termination of the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Termination of the study
UCB reserves the right to temporaril
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
UCB reserves the right to temporarily suspend or prematurel
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y suspend or prematurel
single site, multiple sites, or at all sites at an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
single site, multiple sites, or at all sites at an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
 enrollment with respect to qualit
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 enrollment with respect to qualit
 is prematurely
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 is prematurely terminated or suspended, UCB (or its representative) will inform 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 terminated or suspended, UCB (or its representative) will inform 
 is prematurely terminated or suspended, UCB (or its representative) will inform 
 is prematurely
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 is prematurely terminated or suspended, UCB (or its representative) will inform 
 is prematurely
the investigators/institutions and the regulatory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the investigators/institutions and the regulatory
and the reason(s) for the termination or suspension, in accordance with a
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
and the reason(s) for the termination or suspension, in accordance with a
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
termination or suspension by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
applicable regulatory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
applicable regulatory
all unused study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
all unused study
12.5
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
12.5
The investigator will maintain adequate records for the study, including medical records, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The investigator will maintain adequate records for the study, including medical records, 
la
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
la


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 75of 97
the formal discontinuation of clinical development of the investigational product. 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 
[Section4.9.5]). The investigator will contact UCB for authorization prior to the destruction 
of any study records or in the event of accidental loss or destruction of any study records. The 
investigator will also notify UCB should he/she relocate or move the study-related files to a 
location other than that specified in the sponsor’s study master file.
12.6
Audit and inspection
The investigator will permit study-related audits mandated by UCB, after reasonable notice, 
and inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and well-being of 
the subjects enrolled have been protected, that enrolled subjects (ie, signing consent and 
undergoing study procedures) are appropriate for the study, and that all data relevant for the 
evaluation of the IMP have been processed and reported in compliance with the planned 
arrangements, the protocol, investigational site, and 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).
12.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirementsby the 
investigator, institution, institution staff, or designees of the sponsor will lead to prompt 
action by UCB to secure compliance. Continued noncompliance may result in the termination 
of the site’s involvement in the study.
13
STATISTICS
A description of statistical methods follows and will be described in more de tail in the 
Statistical Analysis Plan (SAP).
13.1
Definition of analysis sets
The primary analysis set for the efficacy data will be the Full Analysis Set (FAS), and will 
include all subjects who were randomized, received at least 1 dose of study medication, and 
had a Baseline and at least 1 post-Baseline assessment of seizure frequency data.
The secondary analysis set for the efficacy data will be the Per Protocol Set (PPS), which 
includes all subjects in the FAS who did not have major protocol deviations.
The Safety Set (SS) will include all randomized subjects who took at least 1 dose of study 
medication. This is the primary analysis set for the analysis of the safety parameters.
The Pharmacokinetic Per-Protocol Set (PK-PPS)will consist of all subjects having provided 
at least 1 measurable postdose plasma sample (with recorded sampling time) on at least 
1visit with documented study medication intake times.
REDACTED COPY 
The investigator will provide direct access to all study
REDACTED COPY 
The investigator will provide direct access to all study do
REDACTED COPY 
 do
The investigator will provide direct access to all study do
The investigator will provide direct access to all study
REDACTED COPY 
The investigator will provide direct access to all study do
The investigator will provide direct access to all study
 is announced, the investigator will 
REDACTED COPY 
 is announced, the investigator will 
Good Clinical Practice
REDACTED COPY 
Good Clinical Practice
-
REDACTED COPY 
-GCP, or local regulatory
REDACTED COPY 
GCP, or local regulatory
investigator, institution, institution staff, or designees of the sponsor will lead to prompt 
REDACTED COPY 
investigator, institution, institution staff, or designees of the sponsor will lead to prompt 
 UCB to secure compliance. Continued noncompliance may
REDACTED COPY 
 UCB to secure compliance. Continued noncompliance may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y UCB, after reasonable notice, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y UCB, after reasonable notice, 
or inspection are to confirm that the rights and well
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
or inspection are to confirm that the rights and wellbeing of 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
being of 
the subjects enrolled have been protected, that enrolled subjects (ie, signing consent and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the subjects enrolled have been protected, that enrolled subjects (ie, signing consent and 
, and that all data relevant for the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, and that all data relevant for the 
tion of the IMP have been processed and reported in compliance with the planned 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
tion of the IMP have been processed and reported in compliance with the planned 
RB/IEC SOPs, I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
RB/IEC SOPs, ICH
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CH
cuments, source records, and source 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
cuments, source records, and source 
 is announced, the investigator will 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 is announced, the investigator will 
GCP, or local regulatory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
GCP, or local regulatory
investigator, institution, institution staff, or designees of the sponsor will lead to prompt 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
investigator, institution, institution staff, or designees of the sponsor will lead to prompt 
 UCB to secure compliance. Continued noncompliance may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 UCB to secure compliance. Continued noncompliance may
of the site’s involvement in the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
of the site’s involvement in the study.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
.
TISTICS
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
TISTICS
of statistical methods follows and will be described in more detail in the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
of statistical methods follows and will be described in more detail in the 
sis Plan (SAP).
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sis Plan (SAP).
Definition of analy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Definition of analy
 anal
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 analys
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ysis set for the efficacy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
is set for the efficacy
include all subjects who were randomized, received at least 1 dose of study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
include all subjects who were randomized, received at least 1 dose of study
a Baseline and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
a Baseline and 
The secondary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The secondary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
includes all subj
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
includes all subj
The Safet
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The Safet
medication. This is the primary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
medication. This is the primary


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 76of 97
13.2
General statistical considerations
Descriptive statistics will be used to provide an overview of the efficacy and safety results. 
For categorical parameters, the number and percentages of subjects in each category will be 
presented. The denominator for percentage will be based on the number of subjects 
appropriate for the purpose of analysis. For continuous parameters, descriptive statistics will 
include n, mean, standard deviation (SD), median, minimum, and maximum. Appropriate 
inferential statistics will be calculated for the primary and selected secondary efficacy 
variables. Baseline values for efficacy and safety variables will be based on the last 
nonmissing data collected prior to the first dose of study medication, unless otherwise noted.
Subjects who prematurely discontinue from the study will be evaluated based on the data 
collected at each visit attended or periodentered.
Further methods pertaining to the summary and analysis of the efficacy, safety, and PK data 
are presented in the following sections, and will be described in more detail in the SAP.
13.3
Planned efficacy analyses
13.3.1
Analysis of the primary efficacy variable
The assessment of efficacy is based on seizure frequency.
The primary efficacy variable is the change in partial-onset seizure frequency per 28days 
from Baseline to the Maintenance Period.
Seizure frequency per 28days will be calculated as ([number of seizures over the specified 
time interval] divided by [number of days in the interval]) multiplied by 28. For subjects who 
prematurely discontinue the study, last observation carried forward method will be applied to 
obtain a seizure frequency estimate for the Maintenance Period.
Seizure frequency will be analyzed using analysis of covariance (ANCOVA) with terms for 
treatment and center (properly pooled), on log-transformed seizure frequency using the 
transformation of ln(X+1), where X is the seizure frequency. Log transformed baseline 
seizure frequency will be used as a covariate. The seizure frequency between treatment and 
placebo will be compared using least squares means(LSMs). The percent reduction over 
placebo will be estimated as 100 x (1 –exp [LSM LCM–LSM placebo]).
It is planned to properly pool centers by geographic location. The final strategy for pooling 
will be determined prior to the unblinding of the study.
13.3.2
Analysis of secondary efficacy variables
The secondary efficacy variables for this study are described in Section4.1.2.
Subjects will be categorized as responders if the reduction in partial-onset seizure frequency 
from the Baseline Period to the appropriate treatment period meets the level specified in the 
given analysis. Response to treatment will be summarized for the proportion of subjects 
experiencing a ≥25% to <50%, 50 to 75%, or >75% reduction in partial-onset seizure 
frequency from the Baseline Period to the Maintenance Period. Proportion of subjects 
experiencing no change in partial-onset seizure frequency (ie, between <25% reduction and 
<25% increase in seizure frequency) and the proportion of subjects experiencing ≥25% 
REDACTED COPY 
 is based on seizure frequency
REDACTED COPY 
 is based on seizure frequency
 variable is the change in partial
REDACTED COPY 
 variable is the change in partial-
REDACTED COPY 
-onset seizure frequency
REDACTED COPY 
onset seizure frequency
s will be calculated as ([number of seizures over the specified 
REDACTED COPY 
s will be calculated as ([number of seizures over the specified 
 [number of day
REDACTED COPY 
 [number of days in the interval]) multiplied by
REDACTED COPY 
s in the interval]) multiplied by
y discontinue the study, last observat
REDACTED COPY 
y discontinue the study, last observat
obtain a seizure frequency estimate for the Maintenance Period.
REDACTED COPY 
obtain a seizure frequency estimate for the Maintenance Period.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 medication, unless otherwise noted.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 medication, unless otherwise noted.
will be evaluated based on the data 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be evaluated based on the data 
, safety
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, safety, and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, and 
detail in the SAP.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
detail in the SAP.
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizure frequency
s will be calculated as ([number of seizures over the specified 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s will be calculated as ([number of seizures over the specified 
s in the interval]) multiplied by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s in the interval]) multiplied by
y discontinue the study, last observat
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y discontinue the study, last observat
obtain a seizure frequency estimate for the Maintenance Period.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
obtain a seizure frequency estimate for the Maintenance Period.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ed using anal
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ed using anal
 pooled), on log
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 pooled), on log
transformation of ln(X+1), where X is the seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
transformation of ln(X+1), where X is the seizure frequency
 will be used as a covariate. The seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 will be used as a covariate. The seizure frequency
placebo will be compared using least squares means
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
placebo will be compared using least squares means
placebo will be estimated as 100 x (1 –
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
placebo will be estimated as 100 x (1 –
It is planned to properl
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
It is planned to properl
will be determined 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be determined 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The secondary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The secondary
Subjects will be categoriz
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subjects will be categoriz
from the Baseline Period to the appropriate treatment period meets the level specified in the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
from the Baseline Period to the appropriate treatment period meets the level specified in the 
given anal
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given anal


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 77of 97
increase in partial-onset seizure frequency from the Baseline Period to the Maintenance 
Period will be presented. These response categories will also be presented from Baseline to 
the Treatment Period.
The difference in responder rate for 50% reduction in partial-onset seizure frequency between 
the LCM treatment group and placebo will be analyzed using a logistic regression model with 
effects for treatment and pooled center. No other statistical testing will be performed for the 
other secondary variables related to reduction in partial-onset seizure frequency.
The number and percentage of subjects experiencing a <50%, 50 to 75%, or >75% reduction 
in seizure frequency from Baseline to each post-Baseline visit will be presented by treatment 
group. The descriptive statistics for percent change in seizure frequency per 28days from 
Baseline to each post-Baseline visit, the Maintenance Period, and entire Treatment and 
Maintenance Periods will be presented by seizure type and treatment group. No inferential 
testing will be performed for these summaries.
The change in seizure frequency per 28 days from Baseline to the Treatment Period, defined 
as the combined Titration and Maintenance Periods, will be summarized by treatment group 
(LCM or placebo) using descriptive statistics. Statistical testing will be performed using an 
ANCOVA model with terms for treatment and pooled center and Baseline seizure frequency 
as a covariate.
The change inseizure frequency by period will also be summarized using descriptive 
statistics by treatment group and seizure type.
For subjects who enter the Maintenance Period, proportion of seizure-free days during the 
Maintenance Period will be calculated and summarized by treatment group descriptively.
For subjects who complete the Maintenance Period, the number and percentage of subjects 
who achieved “seizure-free” status during the Maintenance Period will be tabulated and 
presented by treatment group descriptively.
13.3.3 
Other efficacy analyses
The number and percentage of subjects with each Clinical Global Impression of Change and 
Caregiver’s Global Impression of Change value will be summarized by treatment group.A 
descriptive summary of PedsQL will be provided.No statistical testing will be performed for 
the other efficacy variables.
13.4
Planned safety and other analyses
Descriptive statistics will be used to provide an overview of the safety and PK results.
13.4.1
Safety analyses
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA®) and tabulated by System Organ Class (SOC) and preferred term (PT). 
Treatment emergent AEs will be defined as those events which start on or after the date of 
first study medication administration and within 30days following the date of last study 
medication administration, or whose severity worsens within this time frame. The incidence 
of TEAEs will be presented by SOC and PT. Serious AEs and TEAEs leading to withdrawal 
will also be tabulated and listed.
REDACTED COPY 
ANCOVA model with terms for treatment and pooled center and B
REDACTED COPY 
ANCOVA model with terms for treatment and pooled center and B
 period will also be summarized using descriptive 
REDACTED COPY 
 period will also be summarized using descriptive 
pe.
REDACTED COPY 
pe.
For subjects who enter the Maintenance Period, proportion of seizure
REDACTED COPY 
For subjects who enter the Maintenance Period, proportion of seizure
Maintenance Period will be calculated and summa
REDACTED COPY 
Maintenance Period will be calculated and summa
For subjects who complete the Maintenance Period, the number and percentage of subjects 
REDACTED COPY 
For subjects who complete the Maintenance Period, the number and percentage of subjects 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
or >75% reduction 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
or >75% reduction 
 treatment 
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 treatment 
day
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days from 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s from 
Baseline visit, the Maintenance Period, and entire Treatment and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Baseline visit, the Maintenance Period, and entire Treatment and 
 seizure type and treatment group. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 seizure type and treatment group. No inferential 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
No inferential 
s from Baseline to the Treatment Period, defined 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s from Baseline to the Treatment Period, defined 
eriods, will be summarized by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
eriods, will be summarized by
CM or placebo) using descriptive statistics. Statistical testing will be performed using an 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CM or placebo) using descriptive statistics. Statistical testing will be performed using an 
ANCOVA model with terms for treatment and pooled center and B
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ANCOVA model with terms for treatment and pooled center and B
 period will also be summarized using descriptive 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 period will also be summarized using descriptive 
For subjects who enter the Maintenance Period, proportion of seizure
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
For subjects who enter the Maintenance Period, proportion of seizure
Maintenance Period will be calculated and summa
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Maintenance Period will be calculated and summa
For subjects who complete the Maintenance Period, the number and percentage of subjects 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
For subjects who complete the Maintenance Period, the number and percentage of subjects 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
free” status during the Maintenance Period will be tabulated and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
free” status during the Maintenance Period will be tabulated and 
descriptivel
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descriptivel
Other efficacy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Other efficacy analy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 analy
Other efficacy analy
Other efficacy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Other efficacy analy
Other efficacy
The number and percentage of subjects with each Clinical Global I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The number and percentage of subjects with each Clinical Global I
Caregiver’s Global Impression of Change value will be summarized by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Caregiver’s Global Impression of Change value will be summarized by
descriptive summary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
descriptive summary of PedsQL
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of PedsQL
descriptive summary of PedsQL
descriptive summary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
descriptive summary of PedsQL
descriptive summary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the other efficacy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the other efficacy variables.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 variables.
the other efficacy variables.
the other efficacy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
the other efficacy variables.
the other efficacy
Planned safety
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Planned safety
Descriptive statistics will be used to provide an overview of the safety
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Descriptive statistics will be used to provide an overview of the safety
13.4.1
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
13.4.1
Adverse events will be coded using the Medical 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Adverse events will be coded using the Medical 
(MedDRA®) and tabulated by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(MedDRA®) and tabulated by


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 78of 97
Othervariables assessing safety are: ECG, measurements of laboratory parameters 
(hematology, clinical chemistry, urinalysis, and hormone status) and vital signs (including 
body weight, height and BMI), physical and neurological examination findings, assessments 
of Tanner stage (if applicable), Achenbach CBCL, and BRIEF-P/BRIEF.
Measurement and change from Baseline in continuous parameters (eg, vital signs and 
laboratory measurements) will be summarized using descriptive statistics. When analyzing 
categorical data (eg, overall assessment of 12-lead ECG) the number and percentage of 
subjects in each category will be presentedby treatment group. In addition, shift tables may 
be used to evaluate the number and percentage of subjects having a different post-Baseline
status when compared to their Baseline status.Laboratory, ECG, and vital signs data outside 
of the respective reference ranges will be listed and highlighted.
13.4.2 
Pharmacokinetic analyses
13.4.2.1 
Descriptive statistics of LCM and AED plasma concentrations
The results of LCM and other AEDs plasma concentrations will be described by the method 
of descriptive statistics: arithmetic mean, SD, median, range, geometric mean, and geometric 
coefficient of variation. The evaluations will be done based on separation by LCM dose level 
and study period.
13.4.3
Population pharmacokinetics
Summarization of PK data relative to time after dose will be performed for the overall group 
and separated by AED therapy and possibly age groups.
A population PK modeling of the LCM concentration time data will be performed within the 
NONMEM software. The effects of age, body weight, AED therapy, and other covariates will 
be evaluated. Simulations will be undertaken for estimating dose adaptations leading to the 
same exposure as in adults.
The methods will be described in the DAP (Data Analysis Plan) and the results will be 
reported in a modeling report.
13.4.3.1
Exposure-response
A model-based approach willbe used to describe the relationship between LCM and seizure 
counts data. The PK and PD data will be combined and exploratory analyses will be 
conducted to determine if a dose-response relationship can be demonstrated. Additional 
information will be documented separately in a DAP.
13.5
Handling of protocol deviations
After all CRFs have been retrieved and entered, all queries issued and answered to the extent 
possible, and prior to locking and unblinding the clinical database, a Data Review Meeting 
will be held. Important protocol deviations (ie, those considered to have an impact on 
interpretation of safety, efficacy, or study conduct) will be identified and reviewed by 
appropriate team members.
REDACTED COPY 
Population pharmacokinetics
REDACTED COPY 
Population pharmacokinetics
Summarization of PK data relative to time after dose will be performed for the overall group 
REDACTED COPY 
Summarization of PK data relative to time after dose will be performed for the overall group 
y and possibl
REDACTED COPY 
y and possibly age groups.
REDACTED COPY 
y age groups.
M concentration time 
REDACTED COPY 
M concentration time 
NONMEM software. The effects of age, bod
REDACTED COPY 
NONMEM software. The effects of age, bod
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. In addition, shift tables may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. In addition, shift tables may
Baseline
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Baseline
, ECG, and vital signs data outside 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, ECG, and vital signs data outside 
ED plasma concentrations
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ED plasma concentrations
s of LCM and other AEDs plasma concentrations will be described by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s of LCM and other AEDs plasma concentrations will be described by
of descriptive statistics: arithmetic mean, SD, median, range, geometric mean, and geometric 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
of descriptive statistics: arithmetic mean, SD, median, range, geometric mean, and geometric 
. The evaluations will be done based on separation by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
. The evaluations will be done based on separation by
Summarization of PK data relative to time after dose will be performed for the overall group 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Summarization of PK data relative to time after dose will be performed for the overall group 
y age groups.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y age groups.
M concentration time 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
M concentration time 
NONMEM software. The effects of age, bod
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
NONMEM software. The effects of age, body weight, AED therap
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y weight, AED therap
be evaluated. Simulations will be undertaken for estimating dose adaptations leading to the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
be evaluated. Simulations will be undertaken for estimating dose adaptations leading to the 
will be described in the DAP 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be described in the DAP 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
reported in a modeling report
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
reported in a modeling report.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
.
Exposure
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Exposure-response
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-response
based approach 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
based approach 
counts data. The PK and PD data will be comb
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
counts data. The PK and PD data will be comb
conducted to determine if a dose
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
conducted to determine if a dose
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
information will be documented separatel
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
information will be documented separatel
After all CRFs have been retrieved and entered,
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
After all CRFs have been retrieved and entered,
possible, and prior to locking and unblinding the clinical database, a Data Review Meeting 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
possible, and prior to locking and unblinding the clinical database, a Data Review Meeting 
will be held. I
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will be held. I


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 79of 97
13.6
Handling of dropouts or missing data
As described in Section13.3, for subjects who discontinue prior to the Maintenance Period, 
all available seizure frequency data will be carried forward from the Titration Period for the 
Maintenance Period analysis. For subjects who prematurely discontinue during the 
Maintenance Period, all available seizure frequency data in the Maintenance Period will be 
carried forward for the entire Maintenance Period. Subjects who discontinue prior to any 
efficacy data collection will not be included in the analyses (ie, data will not be carried 
forward from Baseline). The imputation for the seizure frequency data will not carry forward 
into the Transition and Taper Periods.
The impact of missing data on the assessment of primary efficacy will be evaluated with 
sensitivity analyses with further details to be included in the SAP.
No imputation of missing values associated with an individual date or visit is planned for the 
primary safety analysis, with the exception of partial date information for AEs and 
concomitant medications in order to determine whether they are treatment emergent.
13.7
Planned interim analysis and data monitoring
No formal interim analysis for determination of efficacy is planned for this study. To ensure 
subject safety, interim reviews of safety data will be performed using an Independent Data 
Monitoring Committee (IDMC). Serious adverse events and other significant events are 
monitored and will be triaged by the medical monitor and UCB Drug Safety in real time. 
After this triage, events will be passed on to the IDMC as appropriate. In addition, 3 interim 
reviews of safety data by the IDMC are planned when 25%, 50%, and 75% of subjects have 
been randomized and at study completion. The objective, procedures, and timing ofIDMC 
safety assessments to evaluate risk and benefit for subjects in SP0969 will be described in an 
IDMC Charter.
A blinded sample size re-estimation will be performed when 50% of subjects have been 
randomized, completed the study, and have data available for analysis to check the validity of 
these assumptions using interim data from the study. The sample sizere-estimation with 
equal allocation in each arm will be performed using the related residual variance combined 
with Guenther adjustment (Friede and Kieser, 2011). An assessment of the observed dropout 
rate will also be made as part of this analysis, and the potential dropout rate of 14% used for 
calculation of the initial sample size (see Section 13.8) will be modified based on the 
observed rate.
The final sample size will be modified according to the sample size re-estimate and also the 
anticipated dropout rate; however, an upper bound will be applied to reach a maximum 
sample size based on practical and logistical considerations. The initial sample size 
re-estimate using Guenther adjustment will not be adjusted above 149 subjects per treatment 
arm and the original estimated overall study dropout rate will not be adjusted above 24%.
13.8
Determination of sample size
Assuming an effect size of 0.342, in which the effect size was calculated using a 
placebo-subtracted difference of -0.249 and a common SDof 0.73 on the log-transformed 
data, the difference of -0.249 on the log-transformed data is equivalent to approximately 22% 
REDACTED COPY 
is for determination of efficacy
REDACTED COPY 
is for determination of efficacy
 data will be performed using an Independent Data 
REDACTED COPY 
 data will be performed using an Independent Data 
Monitoring Committee (IDMC). Serious adverse events and other significant events are 
REDACTED COPY 
Monitoring Committee (IDMC). Serious adverse events and other significant events are 
y the medical monitor and UCB Drug Safety in real time. 
REDACTED COPY 
y the medical monitor and UCB Drug Safety in real time. 
his triage, events will be passed on to the IDMC as appropriate. In addition,
REDACTED COPY 
his triage, events will be passed on to the IDMC as appropriate. In addition,
y the IDMC are planned when 25%, 50%, and 75% of subjects have 
REDACTED COPY 
y the IDMC are planned when 25%, 50%, and 75% of subjects have 
 completion. The objective, procedures, and timing of
REDACTED COPY 
 completion. The objective, procedures, and timing of
y assessments to evaluate risk and benefit for subjects in SP0969 will be described in an 
REDACTED COPY 
y assessments to evaluate risk and benefit for subjects in SP0969 will be described in an 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 forward 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 forward 
 will be evaluated with 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 will be evaluated with 
No imputation of missing values associated with an individual date or visit is planned for the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
No imputation of missing values associated with an individual date or visit is planned for the 
rmation for AEs and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rmation for AEs and 
 are treatment emergent.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 are treatment emergent.
sis and data monitoring
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sis and data monitoring
 is planned 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 is planned 
 data will be performed using an Independent Data 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 data will be performed using an Independent Data 
Monitoring Committee (IDMC). Serious adverse events and other significant events are 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Monitoring Committee (IDMC). Serious adverse events and other significant events are 
y the medical monitor and UCB Drug Safety in real time. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y the medical monitor and UCB Drug Safety in real time. 
his triage, events will be passed on to the IDMC as appropriate. In addition,
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
his triage, events will be passed on to the IDMC as appropriate. In addition,
y the IDMC are planned when 25%, 50%, and 75% of subjects have 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y the IDMC are planned when 25%, 50%, and 75% of subjects have 
 completion. The objective, procedures, and timing of
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 completion. The objective, procedures, and timing of
y assessments to evaluate risk and benefit for subjects in SP0969 will be described in an 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y assessments to evaluate risk and benefit for subjects in SP0969 will be described in an 
estimation will be performed when 50% of subjects have been 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
estimation will be performed when 50% of subjects have been 
randomized, completed the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
randomized, completed the study, and have data available
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, and have data available
these assumptions using interim data from the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
these assumptions using interim data from the 
equal allocation in each arm will be performed using the related residual variance combined 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
equal allocation in each arm will be performed using the related residual variance combined 
with Guenther adjustment (Friede and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
with Guenther adjustment (Friede and 
rate will also be made as part of this anal
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
rate will also be made as part of this anal
calculation of the initial sample size (see Section 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
calculation of the initial sample size (see Section 
observed rate.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
observed rate.
The final sample size will be modified according to the sample size re
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The final sample size will be modified according to the sample size re
anticipated dropout rate; however, an upper bound will be ap
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
anticipated dropout rate; however, an upper bound will be ap
sample size based on practical and logistical considerations. The initial sample size 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
sample size based on practical and logistical considerations. The initial sample size 
re
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
re-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-estimate using Guenther adjustment will not be adjusted above 149 subjects per treatment 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
estimate using Guenther adjustment will not be adjusted above 149 subjects per treatment 
arm and the original estimated overall stud
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
arm and the original estimated overall stud


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 80of 97
reduction over placebo after exponentiation. With this effect size, power of 80%, and a 
2-sided test at the 5% level of significance, a sample of 135 subjects in each treatment arm 
will be needed.
Assuming a responder rate of 22% and 40% for the placebo and LCM groups, respectively, a 
2-sided continuity corrected Chi-square test at a significance level of 5% will provide 
approximately 87% power with 135 subjects in the placebo group and 135 subjects in the 
LCM group.
To account for an anticipated subject dropout rate of approximately 14%, the planned number 
of subjects to enroll is 154 subjects per treatment arm.
A blinded sample size re-estimation will be performed when 50% of the subjects have been 
randomized, completed the study, and have data for analysisto check the validity of these 
assumptions as described in Section13.7.
14
ETHICS AND REGULATORY REQUIREMENTS
14.1
Informed consent
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki. When possible or as required according to local 
IRB/IEC, assent also has to be obtained from the subject.
Prior to obtaining informed consent, information should be given in a language and at a level 
of complexity understandable to the subject in both oral and written form by the investigator 
(or designee). Each subject and/or subject’s parent/legal guardian 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 parent/legal guardian and by the person who conducted the 
informed consent discussion (investigator or designee). The subject’s parent/legal guardian 
must receive a copy of the signed and dated Informed Consent form. As part of the consent 
process, each subject’s parent/legal guardian 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 (ie, HIPAA) Authorization form.
The subject may withdraw his/her consent to participate in the study at any time.A subject is 
considered as enrolled in the study when he/she has signed the Informed Consent form. A 
CRF must not be started, nor may any study specific procedure be performed for a given 
subject, without having obtained his/her written consent to participate in the study.
REDACTED COPY 
-GCP requirements, and the ethical principles that have their origin in the 
REDACTED COPY 
-GCP requirements, and the ethical principles that have their origin in the 
n of Helsinki. When possible or as required according to local 
REDACTED COPY 
n of Helsinki. When possible or as required according to local 
B/IEC, assent also has to be obtained from the subject.
REDACTED COPY 
B/IEC, assent also has to be obtained from the subject.
Prior to obtaining informed consent, information should be given in a language and at a level 
REDACTED COPY 
Prior to obtaining informed consent, information should be given in a language and at a level 
 understandable to the subje
REDACTED COPY 
 understandable to the subject in both oral and written form by
REDACTED COPY 
ct in both oral and written form by
(or designee). Each subject and/or subject’s parent/legal guardian will have the opportunity
REDACTED COPY 
(or designee). Each subject and/or subject’s parent/legal guardian will have the opportunity
 and its alternatives with the investigator.
REDACTED COPY 
 and its alternatives with the investigator.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 14%, the planned number 
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 14%, the planned number 
ects have been 
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ects have been 
to check the validity
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to check the validity of these 
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 of these 
to check the validity of these 
to check the validity
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to check the validity of these 
to check the validity
Y REQUIREMENTS
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Y REQUIREMENTS
Subject’s informed consent must be obtained and documented in accordance with local 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Subject’s informed consent must be obtained and documented in accordance with local 
-GCP requirements, and the ethical principles that have their origin in the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-GCP requirements, and the ethical principles that have their origin in the 
n of Helsinki. When possible or as required according to local 
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n of Helsinki. When possible or as required according to local 
B/IEC, assent also has to be obtained from the subject.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
B/IEC, assent also has to be obtained from the subject.
Prior to obtaining informed consent, information should be given in a language and at a level 
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Prior to obtaining informed consent, information should be given in a language and at a level 
ct in both oral and written form by
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ct in both oral and written form by
(or designee). Each subject and/or subject’s parent/legal guardian will have the opportunity
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(or designee). Each subject and/or subject’s parent/legal guardian will have the opportunity
 and its alternatives with the investigator.
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 and its alternatives with the investigator.
, the writ
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, the writ
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y the subject’s parent/legal guardian and b
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y the subject’s parent/legal guardian and b
informed consent discussion (investigator or designee). The subject’s parent/legal guardian 
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informed consent discussion (investigator or designee). The subject’s parent/legal guardian 
e signed and dated 
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e signed and dated 
process, each subject’s parent/legal guardian must consent to direct access to the subject’s 
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process, each subject’s parent/legal guardian must consent to direct access to the subject’s 
medical records for stud
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medical records for study-
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y-related monitoring, auditing, IRB/IEC review, and regulatory
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related monitoring, auditing, IRB/IEC review, and regulatory
If the Informed Consent form is amended during the study
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If the Informed Consent form is amended during the study
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applicable) must follow all applicable regulatory requirements pertaining to the approval of 
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applicable) must follow all applicable regulatory requirements pertaining to the approval of 
the amended Informed Consent form b
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the amended Informed Consent form b
All studies conducted at centers in the United States must include the use of a Health 
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All studies conducted at centers in the United States must include the use of a Health 
Insurance Portability
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Insurance Portability
The subject may
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The subject may


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14.2
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 willfill in the subject identifying information and medical 
emergency contact information. The investigator will instruct the subject to keep the card 
with him/her at all times.
14.3
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 forits 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 toeliminate 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.
REDACTED COPY 
applicable), advertisement (if applicable), and all other subject
REDACTED COPY 
applicable), advertisement (if applicable), and all other subject
its review and approval.
REDACTED COPY 
its review and approval.
, the investigator will have written and dated full approval from the 
REDACTED COPY 
, the investigator will have written and dated full approval from the 
 report to the IRB/IEC all changes in the study
REDACTED COPY 
 report to the IRB/IEC all changes in the study
ated problems involving risks to human subjects or others, and any
REDACTED COPY 
ated problems involving risks to human subjects or others, and any
deviations, to eliminate immediate hazards to subjects.
REDACTED COPY 
deviations, to eliminate immediate hazards to subjects.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-GCP, and in accordance with the ethical principles that have their origin in 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-GCP, and in accordance with the ethical principles that have their origin in 
/I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
/IEC that complies 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
EC that complies 
GCP version or applicable country
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
GCP version or applicable country
regulations will be responsible for the initial and continuing review and approval of the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
regulations will be responsible for the initial and continuing review and approval of the 
, the investigator/UCB will forward copies of the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, the investigator/UCB will forward copies of the 
protocol, Informed Consent form, Investigator’s Brochure, investigator’s curriculum vitae (if 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
protocol, Informed Consent form, Investigator’s Brochure, investigator’s curriculum vitae (if 
applicable), advertisement (if applicable), and all other subject
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
applicable), advertisement (if applicable), and all other subject-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-related documents to be used 
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related documents to be used 
its review and approval.
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its review and approval.
, the investigator will have written and dated full approval from the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
, the investigator will have written and dated full approval from the 
 report to the IRB/IEC all changes in the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 report to the IRB/IEC all changes in the study
ated problems involving risks to human subjects or others, and any
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ated problems involving risks to human subjects or others, and any
deviations, to eliminate immediate hazards to subjects.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
deviations, to eliminate immediate hazards to subjects.
The investigator will not make an
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The investigator will not make any changes in the study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y changes in the study
approval, except where necessary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
approval, except where necessary to
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 to
approval, except where necessary to
approval, except where necessary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
approval, except where necessary to
approval, except where necessary eliminate apparent immediate hazards to the subjects. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
eliminate apparent immediate hazards to the subjects. 
For minor changes to a previously
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
For minor changes to a previously
 be possible for the investigator to obtain an expedited review by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 be possible for the investigator to obtain an expedited review by
As part of the IRB/IEC requirements for continuing review of approved studies, the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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 I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
investigator will be responsible for submitting periodic progress reports to the I
(based on IRB/IEC requirements), at intervals appropriate to the degree of subject r
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(based on IRB/IEC requirements), at intervals appropriate to the degree of subject r
involved, but no less than once per 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
involved, but no less than once per 
B/IEC following stud
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B/IEC following stud
UCB (or its representative) will communicate safety
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
UCB (or its representative) will communicate safety
authorities and all active
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
authorities and all active
The appropriate IRB/IEC will also be informed b
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The appropriate IRB/IEC will also be informed b


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05Mar 2015
Clinical Study Protocol
Lacosamide
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Page 82of 97
14.4
Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number 
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 admissions occurring during a subject’s study participation, and autopsy reports 
for deaths occurring during the study).
14.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
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.
15
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the investigator and/or CRO 
agreements, as applicable.
16
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.
Bourgeois BFD,Goodkin HP. Efficacy of antiepileptic drugs in adults vs children: does one 
size fit all? Neurology. 2012;79;1420-1.
Columbia University Medical Center. Columbia-Suicide Severity Rating Scale (2008). 
http://www.cssrs.columbia.edu/. Accessed 19Jun2011.
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.
CHMP/EWP/566/98 Guideline on clinical investigation of medicinal products in the 
treatment of epileptic disorders (EMA) Rev 2, 20 Jan 2010.
REDACTED COPY 
B, the IRB/IEC, and the regulatory
REDACTED COPY 
B, the IRB/IEC, and the regulatory
NCE, INSURANCE, 
REDACTED COPY 
NCE, INSURANCE, AND PUBLICA
REDACTED COPY 
AND PUBLICA
Insurance coverage will be handled according to local requirements.
REDACTED COPY 
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the investigator and/or CRO 
REDACTED COPY 
Finance, insurance, and publication rights are addressed in the investigator and/or CRO 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 (including, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 (including, 
but not limited to, laboratory test result reports, ECG reports, admission/discharge summaries 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
but not limited to, laboratory test result reports, ECG reports, admission/discharge summaries 
 participation, and autopsy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 participation, and autopsy reports 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 reports 
 participation, and autopsy reports 
 participation, and autopsy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 participation, and autopsy reports 
 participation, and autopsy
 and may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 and may also affect the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 also affect the 
 and may also affect the 
 and may
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 and may also affect the 
 and may
fulfilling its primary
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
fulfilling its primary
 be made as an amendment to the protocol and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 be made as an amendment to the protocol and 
B, the IRB/IEC, and the regulatory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
B, the IRB/IEC, and the regulatory authorities (if required), prior to 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 authorities (if required), prior to 
B, the IRB/IEC, and the regulatory authorities (if required), prior to 
B, the IRB/IEC, and the regulatory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
B, the IRB/IEC, and the regulatory authorities (if required), prior to 
B, the IRB/IEC, and the regulatory
AND PUBLICA
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
AND PUBLICA
Insurance coverage will be handled according to local requirements.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the investigator and/or CRO 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Finance, insurance, and publication rights are addressed in the investigator and/or CRO 
ndromic classification in the man
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ndromic classification in the man
Appleton R, Fichtner K, LaMoreaux L, Alexander J, Halsall G, Murray
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Appleton R, Fichtner K, LaMoreaux L, Alexander J, Halsall G, Murray
 in children with refractory
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 in children with refractory
ind, placebo
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ind, placebo-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-controlled study
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
controlled study
-54.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-54.
Bourgeois BFD
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Bourgeois BFD,
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
,Goodkin HP. Efficacy
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Goodkin HP. Efficacy
size fit all? Neurology
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
size fit all? Neurology
Columbia University
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Columbia University
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
http://www.cssrs.columbia.edu/. Accessed 19
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
http://www.cssrs.columbia.edu/. Accessed 19
Commission on Classification and Terminology
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Commission on Classification and Terminology
Epilepsy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Epilepsy


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Lacosamide
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Page 83of 97
CPMP/ICH/135/95 Note for guidance on Good Clinical Practice (EMEA) Jul 2002.Dichek B. 
Epilepsy: an ancient ailment that still eludes a cure. Scrip Magazine. 1999;Feb:9-11.
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, Wylie 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.
Friede T, Kieser M. Blinded sample size recalculation for clinical trials with normal data and 
baseline adjusted analysis. Pharm Stat. 2011;10:8-13.
Glauser TA, Ayala R, Elterman RD, Mitchell WG, Van Orman CB, Gauer LJ, et al. on behalf 
of the N159b Study Group. Double-blind placebo-controlled trial of adjunctive levetiracetam 
in pediatric partial seizures. Neurology. 2006;66:1654-60.
Glauser TA, Nigro M, Sachdeo R, Pasteris LA, Weinstein S, Abou-Khalil B, et al. 
Adjunctive therapy with oxcarbazepine in children with partial seizures: the Oxcarbazepine 
Pediatric Study Group. Neurology. 2000;54:2237-44.
Hadjiloizou SM, Bourgeois BF. Antiepileptic drug treatment in children. Expert Rev 
Neurother. 2007;7:179-193.
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.
Pellock JM, Carman WJ, Thyagarajan V, Daniels T, Morris DL, D’Cruz O.Efficacy of 
antiepileptic drugs in adults predicts efficacy in children: A systematic review Neurology. 
2012;79:1482-9.
Perucca E. Established antiepileptic drugs. Baillieres Clin Neurol. 1996;5:693-722.
Sander JW. New drugs for epilepsy. Curr Opin Neurol. 1998;11:141-8.
Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of 
Life Version 4.0 generic core scales in healthy and patient populations. Med Care. 2001; 
39:800-12.
REDACTED COPY 
tiepileptic drug treatment in children. Expert Rev 
REDACTED COPY 
tiepileptic drug treatment in children. Expert Rev 
 TA. New options for the treatment of epileps
REDACTED COPY 
 TA. New options for the treatment of epileps
 across the spectrum: 
REDACTED COPY 
 across the spectrum: 
Washington, DC: The National Academies Press
REDACTED COPY 
Washington, DC: The National Academies Press
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Friede T, Kieser M. Blinded sample size recalculation for clinical trials with normal data and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Friede T, Kieser M. Blinded sample size recalculation for clinical trials with normal data and 
ala R, Elterman RD, Mitchell WG, Van Orman CB, Gauer L
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ala R, Elterman RD, Mitchell WG, Van Orman CB, Gauer LJ, et al. on behalf 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
J, et al. on behalf 
controlled trial of adjunctive levetiracetam 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
controlled trial of adjunctive levetiracetam 
Glauser TA, Nigro M, Sachdeo R, Pasteris LA, Weinstein S, Abou-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Glauser TA, Nigro M, Sachdeo R, Pasteris LA, Weinstein S, Abou-Khalil B, et al. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Khalil B, et al. 
y with oxcarbazepine in children with partial seizures: the Oxcarbazepine 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y with oxcarbazepine in children with partial seizures: the Oxcarbazepine 
tiepileptic drug treatment in children. Expert Rev 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
tiepileptic drug treatment in children. Expert Rev 
 TA. New options for the treatment of epileps
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 TA. New options for the treatment of epileps
 across the spectrum: 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 across the spectrum: 
Washington, DC: The National Academies Press
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Washington, DC: The National Academies Press
agarajan V,
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
agarajan V,Daniels T, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Daniels T, 
antiepileptic drugs in adults predicts efficacy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
antiepileptic drugs in adults predicts efficacy
ablished antiepileptic drugs. Baillieres Clin Neurol. 1996;5:693
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ablished antiepileptic drugs. Baillieres Clin Neurol. 1996;5:693
Sander JW. New drugs for epileps
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Sander JW. New drugs for epileps
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Varni JW, Seid M, Kurtin PS. PedsQL
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Varni JW, Seid M, Kurtin PS. PedsQL
Life Version 4.0 generic core scales in healthy and patient populations. Med Care. 2001; 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Life Version 4.0 generic core scales in healthy and patient populations. Med Care. 2001; 


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Lacosamide
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Page 84of 97
17
APPENDICES
17.1
Protocol amendment1
Rationale for the amendment
The main purpose of this substantial amendment is to add details to the Statistics section 
regarding sample size re-estimation and statistical evaluation of secondary and other efficacy 
variables based on the clarifications made by the 
 and 
aligned to the wording in the SP0967 protocol (a double-blind, randomized, 
placebo-controlled, parallel-group study to investigate the efficacy and safety of LCM as 
adjunctive therapy in subjects with epilepsy ≥1month to <4 years of age with partial-onset 
seizures). 
Based on previousrecommendations made by the USA FDA, the creatinine clearance has 
beenchanged from less than 50mL/min to less than 30mL/min in Exclusion Criterion 
number 10. In addition, as per request from the 
, Exclusion 
Criterion number 20 has been removed because it is a duplicateof Exclusion Criterion 
number 23. Exclusion criterion number 22 has been reworded to clarify that the excluded 
sodium channelopathies are cardiac.
Modifications and changes
Global changes
The following changes were made throughout the protocol:
The creatinine clearance threshold in the exclusion criterion for s ubjects with impaired 
renal function(Exclusion Criterion number 10) has been lowered from 50mL/min to 
30mL/min.
Exclusion Criterion number 20 has been removed because it is a duplicate of Exclusion 
Criterion number 23.
Exclusion Criterion number 22 has been clarifiedby adding “cardiac” to the sodium 
channelopathies.
In the Statistics section, details related to statistical evaluation of secondary and other 
efficacy variables have been added, and sample size re-estimation texthas been further 
detailed.
Administrative changes: the name of the Study Physician, the Clinical Project Manager, 
and the name of the CRO have been updated, and the Sponsor Declaration has been 
updated for electronic signature.
REDACTED COPY 
made throughout the protocol:
REDACTED COPY 
made throughout the protocol:
creatinine clearance threshold in the exclusion criterion for subjects with impaired 
REDACTED COPY 
creatinine clearance threshold in the exclusion criterion for subjects with impaired 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of LCM as 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 of LCM as 
ears of age with partial
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ears of age with partial-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-onset 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset 
the creatinine clearance 
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the creatinine clearance 
xclusion 
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xclusion C
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Criterion 
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riterion 
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of Exclusion C
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of Exclusion C
Exclusion criterion number 22 has been reworded to clarify
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Exclusion criterion number 22 has been reworded to clarify
made throughout the protocol:
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made throughout the protocol:
creatinine clearance threshold in the exclusion criterion for subjects with impaired 
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creatinine clearance threshold in the exclusion criterion for subjects with impaired 
riterion number 10)
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riterion number 10)
riterion number 20 has been removed because it is a duplicate of 
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riterion number 20 has been removed because it is a duplicate of 
riterion number 22 has been 
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riterion number 22 has been 
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channelopathies.
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channelopathies.
In the Statistics
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In the Statisticssection, details related to statistical ev
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section, details related to statistical ev
efficacy
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efficacy variables have been added, 
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 variables have been added, 
efficacy variables have been added, 
efficacy
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efficacy variables have been added, 
efficacy
detailed
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detailed.
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.
Administrative changes
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Administrative changes
and the name of the CRO have been updat
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and the name of the CRO have been updat
updated for electronic signature
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updated for electronic signature
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Lacosamide
SP0969
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Specific changes
Change #1
SPONSOR DECLARATION
Clinical Project Manager
, BS
_____________________________
Date/Signature
Clinical Trial Biostatistician
, MPH
_____________________________
Date/Signature
Study Physician
 MD
_____________________________
Date/Signature
Clinical ProgramDirector
, BS
_____________________________
Date/Signature
Has been revisedand moved to Section 19:
19SPONSOR 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.
Change #2
STUDY CONTACT INFORMATION
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
Fax:
REDACTED COPY 
_____________________________
REDACTED COPY 
_____________________________
Date/Signature
REDACTED COPY 
Date/Signature
d to Section 19
REDACTED COPY 
d to Section 19
 read and understand this protocol and agree to conduct this 
REDACTED COPY 
 read and understand this protocol and agree to conduct this 
 as outlined in this protocol and according to current Good Clinical Practice.
REDACTED COPY 
 as outlined in this protocol and according to current Good Clinical Practice.
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_____________________________
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_____________________________
_____________________________
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_____________________________
_____________________________
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_____________________________
Date/Signature
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Date/Signature
:
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:
 read and understand this protocol and agree to conduct this 
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 read and understand this protocol and agree to conduct this 
 as outlined in this protocol and according to current Good Clinical Practice.
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 as outlined in this protocol and according to current Good Clinical Practice.
INFORMA
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INFORMA
 Phy
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 Physician
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sician
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Phone:
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Phone:
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Clinical Study Protocol
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SP0969
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Clinical Project Manager
Name:
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Name:
Pharmaceutical Research Associates, Inc.
Address:
Phone:
Fax:
Has been changed to:
Sponsor Study Physician
Name:
 MD
Address:
UCB BIOSCIENCES, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
UNITED STATES
Phone:
Fax:
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
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 MD
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 MD
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UCB BIOSCIENCES, 
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UCB BIOSCIENCES, 
8010 Arco Corporate Drive
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8010 Arco Corporate Drive
Raleigh, NC 27617
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Raleigh, NC 27617
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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
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Clinical Project Manager
Name:
, PhD
Address:
UCB BIOSCIENCES, GmbH.
Alfred-Nobel-Str. 10
40789 Monheim
GERMANY
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Name:
PRAHealth Sciences
Address:
Phone:
Fax:
Change #3
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World:+32 2 386 2421
USA: +1 800 880 6949
Canada:+1 877 582 8842
Japan: +81 3 6864 7400
Email
Global: DS_ICT@ucb.com
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
DVERSE EVENT REPORTING
REDACTED COPY 
DVERSE EVENT REPORTING
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DVERSE EVENT REPORTING
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DVERSE EVENT REPORTING
Serious adverse event reporting (24h)
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Serious adverse event reporting (24h)
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Europe and Rest of the World:
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Europe and Rest of the World:
+1 800 880 6949
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+1 800 880 6949
Canada:
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Canada:
Japan: 
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Japan: 
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Email
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Email
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UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 88of 97
Has been changed to:
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World:+32 2 386 2421
USA: +1 800 880 6949
Canada:+1 877 582 8842
Email
Global: DSICT@ucb.com
Change #4
Section 4.1.3 Other efficacy variables, last bullet
Health care resource use (concomitant AEDs, medical procedures, health care provider 
consultations not related to study, hospitalizations not related to study)
Has been changed to:
Health care resource use (concomitant AEDs, medical procedures, health care provider 
consultations including hospitalizations not foreseen by the protocol)
Change #5
Section 5.2 Schedule of study assessments, Table 5-1footnotes
a
Visit 1 (V1) may occur over more than 1 day; however, all results of Visit 1 assessments 
should be available before T1.
k
The Achenbach CBCL: CBCL/1½ -5 for children 18 months to 5years and 11months of 
age, andCBCL/6-18 for children ≥6years to <17years of age; to be completed by the 
parent(s)/legal representative(s) (estimated completion time 45 minutes).For each subject, 
the same version of the scale that was completed at Visit 2 (CBCL/1½ -5 or CBCL/6-18) 
should be maintained for the duration of the study and should be completed by the same 
parent/legal representative. The Achenbach CBCL will be used only in countries where a 
translated version is available.
Have been changed to:
a
Visit 1 (V1) may occur over more than 1 day; however, all results of Baseline/Visit 1 
assessments should be available before randomization on Visit 2.
m
The Achenbach CBCL: CBCL/1½ -5 for children 18 months to 5years and 11months of 
age, and CBCL/6-18 for children ≥6years to <17years of ageat Screening; to be completed 
by the parent(s)/legal representative(s) (estimated completion time 45minutes). For each 
subject, the same version of the scale that was completed at Visit 2 (CBCL/1½ -5 or 
CBCL/6-18) should be maintained for the duration of the study and should be completed by 
REDACTED COPY 
Health care resource use (concomitant AEDs, medical procedures, health care provider 
REDACTED COPY 
Health care resource use (concomitant AEDs, medical procedures, health care provider 
foreseen by the protocol
REDACTED COPY 
foreseen by the protocol
of study assessments
REDACTED COPY 
of study assessments
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This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Health care resource use (concomitant AEDs, medical procedures, health care provider 
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Health care resource use (concomitant AEDs, medical procedures, health care provider 
, hospitalizations not related to study
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, hospitalizations not related to study
Health care resource use (concomitant AEDs, medical procedures, health care provider 
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Health care resource use (concomitant AEDs, medical procedures, health care provider 
foreseen by the protocol
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foreseen by the protocol
of study assessments
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of study assessments, Table 5
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, Table 5
 occur over more than 1 day
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 occur over more than 1 day
: CBCL
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: CBCL/1½ 
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/1½ 
18 for children 
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18 for children 
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parent(s)/legal representative(s) (estimated completion time 45 minutes).
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parent(s)/legal representative(s) (estimated completion time 45 minutes).
the same version of the scale that was completed at Visit 2 (CBCL
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the same version of the scale that was completed at Visit 2 (CBCL
hould be maintained for the duration of the stud
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hould be maintained for the duration of the stud
parent/legal representative. The Achenbach CBCL will be used only
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parent/legal representative. The Achenbach CBCL will be used only
translated version is available.
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translated version is available.
Have been changed to:
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Have been changed to:
Visit
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Visit
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assessments should be available before 
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assessments should be available before 
m
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m


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 89of 97
the same parent/legal representative. The Achenbach CBCL will be used only in countries 
where a translated version is available.
And the following footnotes have been added:
d
Medical history to include demographics (date of birth [where permitted], age group 
category, age in months and years, race, ethnicity, and gender).
g
The subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout 
the study.
Change #6
Section 5.3 Schematic diagram, Figure 5-1 and Figure 5-2, footnotes
The following footnote has been added:
Note: The subject’s body weight at Baseline (Visit 2) will be used to determine dose 
throughout the study.
Change #7
Section 6.2 Exclusion criteria
10. Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or 
total bilirubin level ≥2times the upper limit of normal (ULN), or creatinine clearance less 
than 50mL/min.
22. Subject has a known sodium channelopathy, such as Brugada syndrome.
Havebeen changed to:
10. Subject has an alanine aminotransferase (ALT), aspartate aminot ransferase (AST), or 
total bilirubin level ≥2times the upper limit of normal (ULN), or creatinine clearance less 
than 30mL/min.
22. Subject has a known cardiac sodium channelopathy, such as Brugada syndrome.
And the following exclusion criterion has been removed:
20. Subject has epilepsy secondary to a progressing cerebral disease or any other 
progressively neurodegenerative disease, such as Rasmussen Syndrome.
Change #8
Section 7.2 Treatments to be administered, third paragraph
At the end of Visit 2, subjects should take the first dose of study medication while in the 
clinic. At each subsequent clinic visit, subjects should take study medication (and any 
concomitant AEDs) at the regular time(s).
REDACTED COPY 
alanine aminotransferase (ALT), aspartate aminotransferase (AST), or 
REDACTED COPY 
alanine aminotransferase (ALT), aspartate aminotransferase (AST), or 
times the upper limit of normal (ULN), or creatinine clearance less 
REDACTED COPY 
times the upper limit of normal (ULN), or creatinine clearance less 
Subject has a known sodium channelopath
REDACTED COPY 
Subject has a known sodium channelopath
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y weight at Baseline (Visit 2) will be used to determine dose throughout 
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y weight at Baseline (Visit 2) will be used to determine dose throughout 
2) will be used to determine dose 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2) will be used to determine dose 
alanine aminotransferase (ALT), aspartate aminotransferase (AST), or 
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alanine aminotransferase (ALT), aspartate aminotransferase (AST), or 
times the upper limit of normal (ULN), or creatinine clearance less 
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times the upper limit of normal (ULN), or creatinine clearance less 
Subject has a known sodium channelopath
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Subject has a known sodium channelopath
. Subject has an alanine aminotransferase (ALT), aspartate aminot ransferase (AST), or 
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. Subject has an alanine aminotransferase (ALT), aspartate aminot ransferase (AST), or 
times the upper limit of normal (ULN), or creatinine clearance less 
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times the upper limit of normal (ULN), or creatinine clearance less 
Subject has a known 
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Subject has a known 
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cardiac 
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cardiac 
d the follow
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d the following exclusion criterion has been removed:
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ing exclusion criterion has been removed:
Subject has epileps
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Subject has epileps
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progressivel
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progressivel
Change 
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Change 
Section 7.2 Treatments to be administered
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Section 7.2 Treatments to be administered


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05Mar 2015
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Lacosamide
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Has been changed to:
At the end of Visit 2, subjects should take the first dose of IMPwhile in the clinic. At each 
subsequent clinic visit, subjects should take the IMP(and any concomitant AEDs) at the 
regular time(s). The subject’s body weight at Baseline (Visit 2) will be used to determine 
dose throughout the study.
Change #9
Section 7.2.1 Titration Period, Section 7.2.3 Transition Period (for subjects who plan to 
enter EP0034), and Section 7.2.4 Taper Period (for subjects not entering EP0034); 
Table7-1, Table 7-2, Table 7-3, Table 7-4, and Table 7-5, footnotes
The following footnote has been added:
Note: The subject’s body weight at Baseline (Visit 2) will be used to determine dose 
throughout the study.
Change #10
Section 8 STUDY PROCEDURES BY VISIT
The following text has been added:
The subject’s body weight at Baseline (Visit 2) will be used to determine dose throughout the 
study.
Change #11
Section 9.1 Specification of efficacy parameters, last bullet
Health care resource use (concomitant AEDs, medical procedures, health care provider 
consultations not related to study, hospitalizations not related to study)
Has been changed to:
Health care resource use (concomitant AEDs, medical procedures, health care provider 
consultations including hospitalizations not foreseen by the protocol)
Change #12
Section 9.2.2.2 Healthcare resource use
For health care resource use parameters, the following will be evaluated: concomitant AEDs, 
medical procedures, health care provider consultations not related to study, hospitalizations 
not related to study.
REDACTED COPY 
y weight at Baseline (Visit 2)
REDACTED COPY 
y weight at Baseline (Visit 2)
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Section 7.2.3 Transition Period (for subjects who plan to 
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Section 7.2.3 Transition Period (for subjects who plan to 
not entering EP0034)
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not entering EP0034); 
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; 
2) will be used to determine dose 
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2) will be used to determine dose 
y weight at Baseline (Visit 2)
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y weight at Baseline (Visit 2)will be used to dete
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will be used to dete
Section 9.1 Specification of efficacy parameters
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Section 9.1 Specification of efficacy parameters
care resource use (concomitant AEDs, medical procedures, health care provider 
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care resource use (concomitant AEDs, medical procedures, health care provider 
consultations not related to study
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consultations not related to study
Has been changed to:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Has been changed to:
Health care resource use (concomitant AEDs, medical procedures, health care provid
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Health care resource use (concomitant AEDs, medical procedures, health care provid
consultations 
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consultations including 
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including 
Change #
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Change #
Section 9.2.2.2 Healthcare resource use
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Section 9.2.2.2 Healthcare resource use
For health care resource use parameters, the following will be evaluated: concomitant AEDs, 
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For health care resource use parameters, the following will be evaluated: concomitant AEDs, 


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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
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Page 91of 97
Has been changed to:
For health care resource use parameters, the following will be evaluated: concomitant AEDs, 
medical procedures, health care provider consultations including hospitalizations not foreseen 
by the protocol.
Change #13
Section 11.1.2 Procedures for reporting and recording adverse events, first paragraph
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. 
Has been changed to:
The subject or subject’s parent(s)/caregiver(s)/legal representative(s) will be given the 
opportunity to report AEs spontaneously. A general prompt will also be given at each study 
visit to detect AEs. 
Change #14
Section 11.9.7 Achenbach CBCL, first paragraph
The Achenbach CBCL is a widely used validated questionnaire to evaluate a child’s 
competencies and behavioral/emotional problems. Behavioral problems will be scored by the 
parent(s)/legal representative(s). Depending on the subject’s age, 2 versions of the CBCL will 
be used. The CBCL/1½-5 checklist is intended for use in children 18 months to 5 years and 
11 months of age. For subjects ≥6 years to <17 years of age, the CBCL/6-18 version willbe 
used. The Achenbach CBCL will only be administered in countries where a translated version 
is available.
Has been changed to:
The Achenbach CBCL is a widely used validated questionnaire to evaluate a child’s 
competencies and behavioral/emotional problems. Behavioral problems will be scored by the 
parent(s)/legal representative(s). Depending on the subject’s age, 2 versions of the CBCL will 
be used. The CBCL/1½-5 checklist is intended for use in children 18 months to 5 years and 
11 months of age. For subjects ≥6 years to <17 years of ageat Screening, the CBCL/6-18 
version will be used. The Achenbach CBCL will only be administered in countries where a 
translated version is available.
Change #15
Section 12.1 Adherence to protocol
The investigator should not deviate from the protocol. In medical emergencies, the 
investigator may use his/her medical judgment and may remove a study participant from 
immediate hazard before notifying UCB (or its representative) and the IRB/IEC in writing 
regarding the type of emergency and the course of action taken.
REDACTED COPY 
, first paragraph
REDACTED COPY 
, first paragraph
y used validated questionnaire to evaluate a child’s 
REDACTED COPY 
y used validated questionnaire to evaluate a child’s 
competencies and behavioral/emotional problems. Behavioral problems will be scored b
REDACTED COPY 
competencies and behavioral/emotional problems. Behavioral problems will be scored b
representative(s). Depending on the subject’s age, 2 versions of the CBCL will 
REDACTED COPY 
representative(s). Depending on the subject’s age, 2 versions of the CBCL will 
5 checklist is intended for use in children 18 months to 5 y
REDACTED COPY 
5 checklist is intended for use in children 18 months to 5 y
ears to <17 
REDACTED COPY 
ears to <17 
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, first paragraph
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, first paragraph
. A general prompt will 
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. A general prompt will 
The subject or subject’s parent(s)/caregiver(s)/legal representative(s) will be given the 
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The subject or subject’s parent(s)/caregiver(s)/legal representative(s) will be given the 
. A general prompt will also be given at each study
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. A general prompt will also be given at each study
y used validated questionnaire to evaluate a child’s 
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y used validated questionnaire to evaluate a child’s 
competencies and behavioral/emotional problems. Behavioral problems will be scored b
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competencies and behavioral/emotional problems. Behavioral problems will be scored b
representative(s). Depending on the subject’s age, 2 versions of the CBCL will 
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representative(s). Depending on the subject’s age, 2 versions of the CBCL will 
5 checklist is intended for use in children 18 months to 5 y
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
5 checklist is intended for use in children 18 months to 5 y
ears to <17 
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ears to <17 
 will only
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 will only be administered in countries where a translated version 
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 be administered in countries where a translated version 
 will only be administered in countries where a translated version 
 will only
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 will only be administered in countries where a translated version 
 will only
 is a widel
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 is a widel
competencies and behavioral/emotional problems. Behavioral problems will be scored b
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competencies and behavioral/emotional problems. Behavioral problems will be scored b
parent(s)/legal representative(s). Depending on the subject’s age, 2 versions of the CBCL will 
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parent(s)/legal representative(s). Depending on the subject’s age, 2 versions of the CBCL will 
be used. The CBCL
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be used. The CBCL
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/1½
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/1½
11 months of age. For sub
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11 months of age. For sub
version will be used. The Achenbach CBCL will only
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version will be used. The Achenbach CBCL will only
translated version is available.
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translated version is available.
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Change #15
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Change #15


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05Mar 2015
Clinical Study Protocol
Lacosamide
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Page 92of 97
Has been changed to:
The investigator should not deviate from the protocol. However, the investigator should take 
any measure necessary in deviation from or not defined by the protocol in order to protect 
clinical study subjects from any immediate hazard to their health and safety. In this case, this 
action should be taken immediately, without prior notification of the regulatory authority, 
IRB/IEC, or sponsor.
After implementation of such measure, the investigator must notify the Clinical Project 
Manager of the sponsor within 24 hours and follow any local regulatory requirements.
Change #16
Section 13.1 Definition of analysis sets, last paragraph
All subjects from the SS with valid LCM plasma concentration data will be included in the 
PK Set (PK-PPS).
Has been changed to:
The Pharmacokinetic Per-Protocol Set (PK-PPS) will consist of all subjects having provided 
at least 1 measurable postdose plasma sample (with recorded sampling time) on at least 
1 visit with documented study medication intake times.
Change #17
Section 13.3.1 Analysis of the primary efficacy variable, last paragraph
It is planned to properly pool centers by geographic location. The final strategy for pooling 
will be determined at the Data Review Meeting.
Has been changed to:
It is planned to properly pool centers by geographic location. The final strategy for pooling 
will be determined prior to the unblinding of the study.
Change #18
Section 13.3.2Analysis of secondary efficacy variables
The secondary efficacy variables for this study are described in Section4.1.2. Inferential 
statistics using similar methods as described in Section 13.3.1 will be calculated for the 
following variables:
Change in seizure frequency per 28days from Baseline tothe entire Treatment Period
Proportion of subjects experiencing a 50% or greater reduction in seizure frequency from 
Baseline to the entire Treatment Period
Additional secondary efficacy variables to be analyzed using inferential statistical methods 
will be described in the SAP.
REDACTED COPY 
-PPS) will consist of all subjects having provided 
REDACTED COPY 
-PPS) will consist of all subjects having provided 
at least 1 measurable postdose plasma sample (with record
REDACTED COPY 
at least 1 measurable postdose plasma sample (with record
 medication intake times.
REDACTED COPY 
 medication intake times.
Section 13.3.1 Analysis of the primary efficacy variable
REDACTED COPY 
Section 13.3.1 Analysis of the primary efficacy variable
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CM plasma concentration data will
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CM plasma concentration data willbe included in the 
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be included in the 
-PPS) will consist of all subjects having provided 
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-PPS) will consist of all subjects having provided 
at least 1 measurable postdose plasma sample (with record
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at least 1 measurable postdose plasma sample (with recorded sampling time) on at least 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ed sampling time) on at least 
 medication intake times.
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 medication intake times.
Section 13.3.1 Analysis of the primary efficacy variable
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Section 13.3.1 Analysis of the primary efficacy variable
pool centers b
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pool centers by 
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y geographic location. The final strategy
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geographic location. The final strategy
will be determined at the Data Review Meet
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will be determined at the Data Review Meet
pool centers b
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pool centers b
will be determined prior to the unblinding of the study
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will be determined prior to the unblinding of the study
13.3.2
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13.3.2
secondary
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secondary
statistics using similar methods as described in Section 13.3.1
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statistics using similar methods as described in Section 13.3.1
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following variables:
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following variables:

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


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05Mar 2015
Clinical Study Protocol
Lacosamide
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Page 93of 97
The number and percentage of subjects experiencing a <50%, 50 to 75%, or >75% reduction 
in seizure frequency from Baseline to each post-Baseline visit, the Maintenance Period, and 
entire Titration and Maintenance Periods will be presented by treatment group. The 
descriptive statistics for percent change in seizure frequency per 28days from Baseline to 
each post-Baseline visit, the Maintenance Period, and entire Treatment and Maintenance 
Periods will be presented by seizure type andtreatment group. For subjects who enter the 
Maintenance Period, proportion of seizure-free days during the Maintenance Period will be 
calculated and summarized by treatment group descriptively.
For subjects who complete the Maintenance Period, the number and percentage of subjects 
who achieved “seizure-free” status during the Maintenance Period will be tabulated and 
presented by treatment group.
Has been changed to:
The secondary efficacy variables for this study are described in Section4.1.2.
Subjects will be categorized as responders if the reduction in partial-onset seizure frequency 
from the Baseline Period to the appropriate treatment period meets the level specified in the 
given analysis. Response to treatment will be summarized for the proportion of subjects 
experiencing a ≥25% to <50%, 50 to 75%, or >75% reduction in partial-onset seizure 
frequency from the Baseline Period to the Maintenance Period. Proportion of subjects 
experiencing no change in partial-onset seizure frequency (ie, between <25% reduction and 
<25% increase in seizure frequency) and the proportion of subjects experiencing ≥25% 
increase in partial-onset seizure frequency from the Baseline Period to the Maintenance 
Period will be presented. These response categories will also be presented from Baseline to 
the Treatment Period.
The difference in responder rate for 50% reduction in partial-onset seizure frequency between 
the LCM treatment group and placebo will be analyzed using a logistic regression model with 
effects for treatment and pooled center. No other statistical testing will be performed for the 
other secondary variables related to reduction in partial-onset seizure frequency.
The number and percentage of subjects experiencing a <50%, 50 to 75%, or >75% reduction 
in seizure frequency from Baseline to each post-Baseline visit will be presented by treatment 
group. The descriptive statistics for percent change in seizure frequency per 28days from 
Baseline to each post-Baseline visit, the Maintenance Period, and entire Treatment and 
Maintenance Periods will be presented by seizure type and treatment group. No inferential 
testing will be performed for these summaries.
The change in seizure frequency per 28 days from Baseline to the Treatment Period, defined 
as the combined Titration and Maintenance Periods, will be summarized by treatment group 
(LCM or placebo) using descriptive statistics. Statistical testing will be performed using an 
ANCOVA model with terms for treatment and pooled center and Baseline seizure frequency 
as a covariate.
The change in seizure frequency by period will also be summarized using descriptive 
statistics by treatment group and seizure type.
REDACTED COPY 
75% reduction in partial
REDACTED COPY 
75% reduction in partial
 from the Baseline Period to the Maintenance Period. Proportion of subjects 
REDACTED COPY 
 from the Baseline Period to the Maintenance Period. Proportion of subjects 
onset seizure frequency
REDACTED COPY 
onset seizure frequency
) and the proportion of subjects experiencing 
REDACTED COPY 
) and the proportion of subjects experiencing 
onset seizure frequency
REDACTED COPY 
onset seizure frequency from the Baseline Period to the Maintenance 
REDACTED COPY 
 from the Baseline Period to the Maintenance 
onset seizure frequency from the Baseline Period to the Maintenance 
onset seizure frequency
REDACTED COPY 
onset seizure frequency from the Baseline Period to the Maintenance 
onset seizure frequency
Period will be presented. These response categories will also be presen
REDACTED COPY 
Period will be presented. These response categories will also be presen
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
For subjects who complete the Maintenance Period, the number and percentage of subjects 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
For subjects who complete the Maintenance Period, the number and percentage of subjects 
free” status during the Maintenance Period will be tabulated and 
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free” status during the Maintenance Period will be tabulated and 
4.1.2
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4.1.2
if the reduction in partial
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if the reduction in partial-
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-onset seizure frequency
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onset seizure frequency
from the Baseline Period to the appropriate treatment period meets the level specified in the 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
from the Baseline Period to the appropriate treatment period meets the level specified in the 
is. Response to treatment will be summarized for the proportion of
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
is. Response to treatment will be summarized for the proportion of
75% reduction in partial
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75% reduction in partial
 from the Baseline Period to the Maintenance Period. Proportion of subjects 
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 from the Baseline Period to the Maintenance Period. Proportion of subjects 
onset seizure frequency
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onset seizure frequency (ie, between <25% re
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 (ie, between <25% re
onset seizure frequency (ie, between <25% re
onset seizure frequency
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
onset seizure frequency (ie, between <25% re
onset seizure frequency
) and the proportion of subjects experiencing 
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) and the proportion of subjects experiencing 
 from the Baseline Period to the Maintenance 
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 from the Baseline Period to the Maintenance 
Period will be presented. These response categories will also be presen
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Period will be presented. These response categories will also be presen
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difference in responder rate for 50% reduction in partial-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
difference in responder rate for 50% reduction in partial-
CM treatment group and placebo will be analy
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CM treatment group and placebo will be analy
ooled center. No other statistical testing will be performed for the 
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ooled center. No other statistical testing will be performed for the 
 variables related to reduction in partial-
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 variables related to reduction in partial-
The number and percentage of subjects experiencing a <50%, 50 to 75%, or >75% reduction 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The number and percentage of subjects experiencing a <50%, 50 to 75%, or >75% reduction 
 from Baseline to each post
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 from Baseline to each post
group. The descriptive statistics for percent change in seizure frequency
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group. The descriptive statistics for percent change in seizure frequency
Baseline to each post
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Baseline to each post
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Maintenance Periods will be presented b
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Maintenance Periods will be presented b
testing will be performed for these summaries.
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testing will be performed for these summaries.
The change in seizure frequency
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The change in seizure frequency
as the combined Titration an
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as the combined Titration an
(L
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
(LCM or placebo) using descriptive statistics. Statistical testing will be performed using an 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
CM or placebo) using descriptive statistics. Statistical testing will be performed using an 
ANCOVA model with terms for treatment and pooled center and B
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ANCOVA model with terms for treatment and pooled center and B


UCB
05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 94of 97
For subjects who enter the Maintenance Period, proportion of seizure-free days during the 
Maintenance Period will be calculated and summarized by treatment group descriptively.
For subjects who complete the Maintenance Period, the number and percentage of subjects 
who achieved “seizure-free” status during the Maintenance Period will be tabulated and 
presented by treatment group descriptively.
Change #19
Section 13.3.3 Other efficacy analyses
The number and percentage of subjects with each Clinical Global Impression of Change and 
Caregiver’s Global Impression of Change value will be summarized by treatment group. A 
descriptivesummary of PedsQL will be provided.
Has been changed to:
The number and percentage of subjects with each Clinical Global Impression of Change and 
Caregiver’s Global Impression of Change value will be summarized by treatment group. A 
descriptive summary ofPedsQL will be provided.No statistical testing will be performed for 
the other efficacy variables.
Change #20
Section 13.7 Planned interim analysis and data monitoring
To ensure subject safety, interim reviews of safety data will be performed using an 
Independent Data Monitoring Committee (IDMC). Serious adverse events and other 
significant events are monitored and will be triaged by the medical monitor and UCB Drug 
Safety in real time. After this triage, events will be passed on to the IDMC as appropriate. In 
addition, 3interim reviews of safety data by the IDMC are planned when 25%, 50%, and 
75% of subjects have been randomized and at study completion. The objective, procedures, 
and timing of IDMC safety assessments to evaluate risk and benefit for subjects in SP0969 
will be described in an IDMC Charter.
Has been changed to:
No formal interim analysis for determination of efficacy is planned for this study. To ensure 
subject safety, interim reviews of safety data will be performed using an Independent Data 
Monitoring Committee (IDMC). Serious adverse events and other significant events are 
monitored and will be triaged by the medical monitor and UCB Drug Safety in real time. 
After this triage, events will be passed on to the IDMC as appropriate. In addition, 3interim 
reviews of safety data by the IDMC are planned when 25%, 50%, and 75% of subjects have 
been randomized and at study completion. The objective, procedures, and timing of IDMC 
safety assessments to evaluate risk and benefit for subjects in SP0969 will be described in an 
IDMC Charter.
A blinded sample size re-estimation will be performed when 50% of subjects have been 
randomized, completed the study, and have data available for analysis to check the validity of 
REDACTED COPY 
Section 13.7 Planned interim analysis and data monitoring
REDACTED COPY 
Section 13.7 Planned interim analysis and data monitoring
y, interim reviews of safet
REDACTED COPY 
y, interim reviews of safet
Independent Data Monitoring Committee (IDMC). Serious adverse events and other 
REDACTED COPY 
Independent Data Monitoring Committee (IDMC). Serious adverse events and other 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
mpression of Change and 
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mpression of Change and 
 treatment group. A 
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 treatment group. A 
The number and percentage of subjects with each Clinical Global I
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The number and percentage of subjects with each Clinical Global Impression of Change and 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
mpression of Change and 
Caregiver’s Global Impression of Change value will be summarized by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Caregiver’s Global Impression of Change value will be summarized by
No statistical testing will be performed for 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
No statistical testing will be performed for 
Section 13.7 Planned interim analysis and data monitoring
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Section 13.7 Planned interim analysis and data monitoring
y, interim reviews of safet
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y, interim reviews of safet
Independent Data Monitoring Committee (IDMC). Serious adverse events and other 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Independent Data Monitoring Committee (IDMC). Serious adverse events and other 
significant events are monitored and will be triaged by
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
significant events are monitored and will be triaged by
 in real time. After this triage, events will be passed on to the IDMC as appropri
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 in real time. After this triage, events will be passed on to the IDMC as appropri
interim reviews of safet
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interim reviews of safety data b
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y data b
75% of subjects have been randomized and at study completion. The objective, procedures, 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
75% of subjects have been randomized and at study completion. The objective, procedures, 
and timing of IDMC safety
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
and timing of IDMC safety assessments to evaluate risk and benefit for su
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
 assessments to evaluate risk and benefit for su
and timing of IDMC safety assessments to evaluate risk and benefit for su
and timing of IDMC safety
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
and timing of IDMC safety assessments to evaluate risk and benefit for su
and timing of IDMC safety
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will be described in an 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
will be described in an IDMC Charter.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
IDMC Charter.
Has been changed to:
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Has been changed to:
No formal interim anal
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
No formal interim anal
subject safet
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
subject safety, interim reviews of safety data will be performed using an Independent 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y, interim reviews of safety data will be performed using an Independent 
Monitoring Committee (IDMC). Serious adverse events and other significant events are 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Monitoring Committee (IDMC). Serious adverse events and other significant events are 
monitored and will be triaged b
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monitored and will be triaged b
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After this triage, events will be passed on to the IDMC as appropriate. In addi
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
After this triage, events will be passed on to the IDMC as appropriate. In addi
reviews of safet
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
reviews of safet
been randomized and at study
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been randomized and at study


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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 95of 97
these assumptions using interim data from the study. The sample size re-estimation with 
equal allocation in each arm will be performed using the related residual variance combined 
with Guenther adjustment (Friede and Kieser, 2011). An assessment of the observed dropout 
rate will also be made as part of this analysis, and the potential dropout rate of 14% used for 
calculation of the initial sample size (see Section 13.8) will be modified based on the 
observed rate.
The final sample size will be modified according to the sample size re-estimate and also the 
anticipated dropout rate; however, an upper bound will be applied to reach a maximum 
sample size based on practical and logistical considerations. The initial sample size 
re-estimate using Guenther adjustment will not be adjusted above 149 subjects per treatment 
arm and the original estimated overall study dropout rate will not be adjusted above 24%.
Change #21
Section 13.8 Determination of sample size, last paragraph
A blinded sample size re-estimation will be performed to check the validity of these 
assumptions using interim data from the study. A blinded estimate of variance for the change 
in partial-onset seizure frequency per 28days from Baseline to the Maintenance Period will 
be calculated.
Has been changed to:
A blinded sample size re-estimation will be performed when 50% of the subjects have been 
randomized, completed the study, and have data for analysisto check the validity of these 
assumptions as described in Section 13.7.
REDACTED COPY 
y. A blinded estimate of variance for the change 
REDACTED COPY 
y. A blinded estimate of variance for the change 
s from Baseline to the Maintenance Period will 
REDACTED COPY 
s from Baseline to the Maintenance Period will 
-estimation will be performed when 50% of the subjects have been 
REDACTED COPY 
-estimation will be performed when 50% of the subjects have been 
, and have data for anal
REDACTED COPY 
, and have data for anal
REDACTED COPY 
13.7
REDACTED COPY 
13.7
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
subjects per treatment 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
subjects per treatment 
y dropout rate will not be adjusted above 24%.
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y dropout rate will not be adjusted above 24%.
-estimation will be performed to check the valid
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-estimation will be performed to check the valid
y. A blinded estimate of variance for the change 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
y. A blinded estimate of variance for the change 
s from Baseline to the Maintenance Period will 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
s from Baseline to the Maintenance Period will 
-estimation will be performed when 50% of the subjects have been 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
-estimation will be performed when 50% of the subjects have been 
, and have data for anal
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, and have data for anal
13.7
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13.7.
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.


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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 96of 97
18
DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and 
local laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects 
of this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be 
treated confidentially, and will not be made available to third parties without prior 
authorization by UCB.
All rights of publication of the results reside with UCB, unless other agreements were made 
in a separate contract.
Investigator:
__________________________________
Printed name
__________________________________
Date/Signature
REDACTED COPY 
__________________________________
REDACTED COPY 
__________________________________
Date/Signature
REDACTED COPY 
Date/Signature
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The objectives and content of this protocol as well as the results deriving from it will be 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
The objectives and content of this protocol as well as the results deriving from it will be 
ot be made available to third parties without prior 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
ot be made available to third parties without prior 
All rights of publication of the results reside with UCB, unless other agreements were made 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
All rights of publication of the results reside with UCB, unless other agreements were made 
__________________________________
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
__________________________________
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Date/Signature
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
Date/Signature


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05Mar 2015
Clinical Study Protocol
Lacosamide
SP0969
Confidential
Page 97of 97
19 
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. 


REDACTED COPY 
REDACTED COPY 
REDACTED COPY 
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SAP_000.pdf: 
UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 1 of 96
STATISTICAL ANALYSIS PLAN 
Study: SP0969
Product: Lacosamide
A MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, 
PARALLEL-GROUP STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF 
LACOSAMIDE AS ADJUNCTIVE THERAPY IN SUBJECTS WITH EPILEPSY ≥4 YEARS 
TO <17 YEARS OF AGE WITH PARTIAL-ONSET SEIZURES
SAP/Amendment Number
Date
Final SAP
11 Sep 2014
SAP – Amendment 1
13 May 2016
SAP – Amendment 2
09 Feb 2017
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 
2014
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2014
May
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 2 of 96
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................7
1
INTRODUCTION .............................................................................................................9
2
PROTOCOL SUMMARY.................................................................................................9
2.1
Study objectives.......................................................................................................9
2.1.1
Primary objective...........................................................................................9
2.1.2
Secondary objective.......................................................................................9
2.1.3
Other objective...............................................................................................9
2.2
Study variables.........................................................................................................9
2.2.1
Efficacy variables ..........................................................................................9
2.2.1.1
Primary efficacy variable.....................................................................9
2.2.1.2
Secondary efficacy variables ...............................................................9
2.2.1.3
Other efficacy variables .....................................................................10
2.2.2
Safety variables............................................................................................10
2.2.2.1
Primary safety variables.....................................................................10
2.2.2.2
Other safety variables.........................................................................10
2.2.3
Pharmacokinetic variables...........................................................................10
2.3
Study design and conduct ......................................................................................11
2.4
Determination of sample size.................................................................................12
2.4.1
Blinded sample size re-estimation procedure ..............................................13
3
DATA ANALYSIS CONSIDERATIONS......................................................................13
3.1
General presentation of summaries and analyses ..................................................13
3.2
General study level definitions ..............................................................................14
3.2.1
Analysis time points.....................................................................................14
3.2.1.1
Last dose of study medication............................................................14
3.2.1.2
Relative day .......................................................................................14
3.2.2
Study periods ...............................................................................................14
3.2.3
Mapping of assessments performed at Early Termination Visit..................15
3.2.4
Last Visit......................................................................................................15
3.3
Definition of Baseline values.................................................................................16
3.4
Protocol deviations.................................................................................................16
3.5
Analysis sets...........................................................................................................16
3.5.1
Safety Set .....................................................................................................16
3.5.2
Full Analysis Set..........................................................................................16
3.5.3
Per Protocol Set ...........................................................................................17
3.5.4
Pharmacokinetic Per Protocol Set................................................................17
3.6
Treatment assignment and treatment groups .........................................................17
3.7
Center pooling strategy..........................................................................................17
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 3 of 96
3.8
Coding dictionaries ................................................................................................17
3.9
Changes to protocol-defined analyses ...................................................................17
4
STATISTICAL/ANALYTICAL ISSUES.......................................................................17
4.1
Adjustments for covariates ....................................................................................17
4.2
Handling of dropouts or missing data....................................................................17
4.2.1
Missing data.................................................................................................17
4.2.2
Incomplete dates for adverse events and concomitant medications ............18
4.2.3
Definition of concomitant medication in case of missing dates ..................18
4.2.4
Incomplete dates for the last administration of study medication ...............19
4.2.5
Incomplete dates for seizure diary data .......................................................19
4.2.6
General imputation rule for incomplete dates..............................................19
4.3
Interim analyses and data monitoring....................................................................20
4.4
Multicenter studies.................................................................................................20
4.5
Multiple comparisons/multiplicity.........................................................................20
4.6
Use of an efficacy subset of subjects .....................................................................20
4.7
Active-control studies intended to show equivalence............................................20
4.8
Examination of subgroups .....................................................................................20
5
STUDY POPULATION CHARACTERISTICS.............................................................21
5.1
Subject disposition.................................................................................................21
5.2
Protocol deviations.................................................................................................21
6
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................21
6.1
Demographics and other Baseline characteristics..................................................21
6.2
Medical history and concomitant diseases.............................................................22
6.2.1
Medical history ............................................................................................22
6.2.2
Concomitant diseases and conditions ..........................................................22
6.3
History of epilepsy.................................................................................................22
6.3.1
History of seizure types ...............................................................................22
6.3.2
History of seizure characteristics.................................................................22
6.3.3
Historical seizure count ...............................................................................23
6.4
Prior and concomitant medications........................................................................23
6.4.1
Number of Lifetime AEDs ..........................................................................23
6.4.2
Number of AEDs taken prior to the Baseline Period...................................23
6.4.3
AEDs taken during the Baseline Period ......................................................23
6.4.4
Number of AEDs taken on day of first dose of study medication...............23
6.4.5
Concomitant AEDs......................................................................................24
6.4.6
Non-AEDs taken prior to the Baseline Period.............................................24
6.4.7
Non-AEDs taken during the Baseline Period ..............................................24
6.4.8
Concomitant Non-AEDs..............................................................................24
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 4 of 96
7
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................24
8
EFFICACY ANALYSES ................................................................................................25
8.1
Statistical analysis of the primary efficacy variable ..............................................25
8.1.1
Derivations of primary efficacy variable.....................................................25
8.1.2
Primary analysis of the primary efficacy variable.......................................26
8.1.3
Secondary analyses of the primary efficacy variable ..................................26
8.1.4
Supportive and sensitivity analyses of the primary efficacy variable .........26
8.2
Statistical analysis of the secondary efficacy variables .........................................26
8.2.1
Change in partial-onset seizure frequency per 28 days from Baseline to 
entire Treatment Period ...............................................................................27
8.2.2
Proportion of responders, where a responder is a subject experiencing a 
50% or greater reduction in partial-onset seizure frequency from Baseline 
to end of Maintenance Period......................................................................27
8.2.3
Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or 
>75% reduction in partial-onset seizure frequency from Baseline to end of 
Maintenance Period .....................................................................................28
8.2.4
Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or 
>75% reduction in partial-onset seizure frequency from Baseline to entire 
Treatment Period..........................................................................................28
8.2.5
Proportion of subjects experiencing no change in partial-onset seizure 
frequency from Baseline to entire Treatment Period...................................29
8.2.6
Proportion of subjects experiencing an increase in partial-onset seizure 
frequency from Baseline to entire Treatment Period...................................29
8.2.7
Change in partial-onset seizure frequency per 28 days from Baseline to the 
entire Treatment Period by seizure type ......................................................29
8.2.8
Proportion of seizure-free days during Maintenance Period .......................30
8.2.9
Proportion of subjects who achieved “seizure-free” status for subjects who 
completed the Maintenance Period..............................................................30
8.3
Analysis of other efficacy variables.......................................................................30
8.3.1
Clinical Global Impression of Change.........................................................30
8.3.2
Caregiver’s Global Impression of Change...................................................31
8.3.3
PedsQL assessment......................................................................................31
8.3.4
Concomitant medical procedures.................................................................32
8.3.5
Healthcare provider consultations ...............................................................32
8.3.6
Hospital stays and emergency room  visits..................................................32
9
PHARMACOKINETICS.................................................................................................33
9.1
Descriptive statistics of LCM and AED plasma concentrations............................33
9.2
Population pharmacokinetics.................................................................................33
9.3
Exposure-response.................................................................................................34
10
SAFETY ANALYSES.....................................................................................................34
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 5 of 96
10.1
Extent of exposure .................................................................................................34
10.2
Adverse events.......................................................................................................35
10.3
Clinical laboratory evaluations ..............................................................................36
10.4
Vital signs, physical findings, and other observations related to safety................37
10.4.1
Vital signs, body weight, height, BMI, and head circumference.................37
10.4.2
Electrocardiograms ......................................................................................39
10.4.3
Physical examination ...................................................................................40
10.4.3.1
Complete physical examination.........................................................40
10.4.3.2
Brief physical examination ................................................................41
10.4.4
Neurological examination............................................................................41
10.4.4.1
Complete neurological examination ..................................................41
10.4.4.2
Brief neurological examination..........................................................41
10.4.5
Vagus nerve stimulation ..............................................................................41
10.4.6
Tanner stage assessment ..............................................................................42
10.4.7
Achenbach Child Behavior Checklist..........................................................42
10.4.8
Assessment of suicidality.............................................................................44
10.4.9
BRIEF-P and BRIEF assessment.................................................................44
10.4.9.1
BRIEF-P scores..................................................................................44
10.4.9.2
BRIEF scores .....................................................................................45
11
REFERENCES ................................................................................................................47
12
APPENDICES .................................................................................................................48
12.1
Marked abnormality criteria for laboratory data....................................................48
12.1.1
Marked abnormality criteria for hematology data .......................................48
12.1.2
Marked abnormality criteria for chemistry data ..........................................49
12.2
Other significant adverse events............................................................................53
13
AMENDMENTS TO THE STATISTICAL ANALYSIS PLAN....................................54
13.1
Amendment 1.........................................................................................................54
13.2
Amendment 2.........................................................................................................85
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE.....................................................96
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09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 6 of 96
LIST OF TABLES
Table 10‒1:
Vital Signs Abnormality .............................................................................38
Table 10‒2:
Electrocardiogram Abnormality Criteria.....................................................40
Table 10‒3:
CBCL/1½-5..................................................................................................42
Table 10‒4:
CBCL/6-18...................................................................................................43
Table 10‒5:
BRIEF-P questionnaire scoring ...................................................................44
Table 10‒6:
BRIEF questionnaire scoring.......................................................................45
Table 12‒1:
Hematology abnormality criteria.................................................................48
Table 12‒2:
Chemistry abnormality criteria ....................................................................49
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 7 of 96
LIST OF ABBREVIATIONS
AE
adverse event
AED
antiepileptic drug 
ALT
alanine aminotransferase
AST
aspartate aminotransferase
ANCOVA
analysis of covariance
bid
twice daily
BMI
body mass index
BP
blood pressure 
BRIEF®
Behavior Rating Inventory of Executive Function®
BRIEF®-P
Behavior Rating Inventory of Executive Function®-
Preschool Version
CBCL
Child Behavior Checklist
CI
confidence interval
CSR
Clinical Study Report
C-SSRS
Columbia-Suicide Severity Rating Scale
CTStat
Clinical Trial Biostatistician
CV
coefficient of variation
DAP
Data Analysis Plan
DBP
diastolic blood pressure
DEM
Data Evaluation Meeting
ECG
electrocardiogram
eCRF
electronic Case Report form
ETV
Early Termination Visit
FAS
Full Analysis Set
HRQoL
health-related quality of life
IDMC
Independent Data Monitoring Committee
IVRS
Interactive Voice Response System
LCM
lacosamide
LSM
least squares mean
MA
markedly abnormal
MedDRA®
Medical Dictionary for Regulatory Activities
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09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 8 of 96
PBO
placebo
PD
pharmacodynamic
PedsQL
Pediatric Quality of Life Inventory
PK
pharmacokinetic
PK-PPS
Pharmacokinetic Per Protocol Set
PPS
Per Protocol Set
PT
preferred term
SBP
systolic blood pressure
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
SOC
system organ class
SPD
Specification of Protocol Deviations
SS
Safety Set
TEAE
treatment-emergent adverse event
TEMA
treatment-emergent markedly abnormal
VNS
vagus nerve stimulation
WHODD
World Health Organization Drug Dictionary
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 9 of 96
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 SP0969. 
2
PROTOCOL SUMMARY
2.1
Study objectives
2.1.1
Primary objective

To evaluate the efficacy of lacosamide (LCM) administered concomitantly with 1 to ≤3 
antiepileptic drugs (AEDs) in subjects with epilepsy ≥4 years to <17 years of age who 
currently have uncontrolled partial-onset seizures
2.1.2
Secondary objective

To evaluate the safety and tolerability of LCM in subjects ≥4 years to <17 years of age
2.1.3
Other objective

To evaluate the pharmacokinetics (PK) of LCM in subjects ≥4 years to <17 years of age
2.2
Study variables
2.2.1
Efficacy variables
The assessment of efficacy is based on partial-onset seizure frequency.
2.2.1.1
Primary efficacy variable
The primary efficacy variable is:

Change in partial-onset seizure frequency per 28 days from Baseline to the Maintenance 
Period
2.2.1.2
Secondary efficacy variables
The secondary efficacy variables include the following:

Proportion of responders, where a responder is a subject experiencing a 50% or greater 
reduction in partial-onset seizure frequency from Baseline to the Maintenance Period

Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or >75% reduction in 
partial-onset seizure frequency from Baseline to the end of Maintenance Period

Change in partial-onset seizure frequency per 28 days from Baseline to the entire treatment 
(ie, Titration+Maintenance Periods)

Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or >75% reduction in 
partial-onset seizure frequency from Baseline to the entire treatment (ie, 
Titration+Maintenance Periods)

Proportion of subjects experiencing no change in partial-onset seizure frequency (between 
<25% reduction and <25% increase) from Baseline to the entire treatment (ie, 
Titration+Maintenance Periods)
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09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 10 of 96

Proportion of subjects experiencing an increase in partial-onset seizure frequency of ≥25% 
from Baseline to the entire treatment (ie, Titration+Maintenance Periods)

Change in partial-onset seizure frequency per 28 days from Baseline to the entire treatment 
(ie, Titration+Maintenance Periods) by seizure type

Proportion of seizure-free days during the Maintenance Period for subjects who entered the 
Maintenance Period

Proportion of subjects who achieved “seizure-free” status (yes/no) for subjects who 
completed the Maintenance Period
2.2.1.3
Other efficacy variables
Other efficacy variables to be examined include:

Clinical Global Impression of Change at the end of the Maintenance Period

Caregiver’s Global Impression of Change at the end of the Maintenance Period

Quality of life assessments (PedsQL)

Health care resource use (concomitant AEDs, medical procedures, health care provider 
consultations including hospitalizations not foreseen by the protocol)  
2.2.2
Safety variables
2.2.2.1
Primary safety variables
Safety and tolerability will be assessed using the following primary variables:

Adverse events (AEs) reported spontaneously by the subject and/or caregiver (including 
parent/legal guardian) or observed by the investigator

Subject withdrawals due to AEs
2.2.2.2
Other safety variables
The other safety variables include:

Changes in hematology, clinical chemistry, and endocrinology parameters

Changes in 12-lead electrocardiograms (ECGs)

Changes in vital sign measurements (ie, blood pressure [BP] and pulse rate)

Physical and neurological examination findings

Changes in body weight, height, and calculated body mass index

Behavioral assessments (Achenbach Child Behavior Checklist/1½-5 [CBCL/1½-5] or 
CBCL/6-18)

Cognitive function assessments (BRIEF-P/BRIEF)
2.2.3
Pharmacokinetic variables
Plasma concentrations of LCM and concomitant AEDs will be obtained in order to:

Develop a population PK model of LCM
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 11 of 96

Investigate the effect of LCM on the steady-state plasma concentrations of concomitant 
AEDs

Investigate the correlation between LCM plasma concentrations and efficacy or safety 
2.3
Study design and conduct
This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group 
study to evaluate the efficacy and safety of LCM (LCM 8mg/kg/day to 12mg/kg/day [oral 
solution] for subjects weighing <30kg, LCM 6mg/kg/day to 8mg/kg/day [oral solution] for 
subjects weighing ≥30kg to <50kg, and LCM 300mg/day to 400mg/day [tablets] for subjects 
weighing ≥50kg, or matching placebo) as adjunctive therapy in subjects with epilepsy ≥4 years 
to <17 years of age with uncontrolled partial-onset seizures. Subjects weighing ≥50kg who are 
unable or unwilling to swallow tablets may receive LCM oral solution. However, they are not 
permitted to exceed the maximum dose of LCM 400mg/day.
A total of approximately 300 subjects are planned to be randomized at approximately 155 sites. 
The study will be conducted in the 
 
region with the possibility to expand the study to other countries and regions if deemed 
necessary.
Stratification of subjects by age category is planned to ensure that an appropriate number of 
subjects will be included in each age range. The age categories are as follows:

At least 100 subjects ≥4 years to <12 years of age

At least 100 subjects ≥12 years to <17 years of age
Subjects with uncontrolled partial-onset seizures will be enrolled into an 8-week Baseline Period. 
At the end of the Baseline Period (Visit 2), eligible subjects will be randomized in a double-blind 
manner to 1 of 2 parallel treatment arms: LCM or placebo in a 1:1 ratio. At the end of Visit 2, 
subjects should take the first dose of study medication while in the clinic. At each subsequent 
clinic visit, subjects should take study medication (and any concomitant AEDs) at the regular 
times. Study medication will be administered orally bid at approximately 12-hour intervals in the 
morning and in the evening.
Eligible subjects will enter a 6-week Titration Period (with study medication dosing flexibility 
allowed based on tolerability) to achieve the target Maintenance Period dose (LCM 8mg/kg/day 
to 12mg/kg/day for subjects weighing <30kg, LCM 6mg/kg/day to 8mg/kg/day for subjects 
weighing ≥30kg to <50kg, and LCM 300mg/day to 400mg/day for subjects weighing ≥50kg, or 
matching placebo). Subjects must achieve the minimum target dose for their body weight 
category for the final 3 days of the Titration Period to be eligible for entry into the Maintenance 
Period. If it becomes apparent that a subject will not be able to reach the minimum target dose, 
then the subject should be withdrawn from the study and enter the Taper Period. 
Subjects who achieved at least the minimum target study medication (LCM or matching placebo) 
dose for the final 3 days of the Titration Period will enter a 10-week Maintenance Period on the 
study medication dose achieved on the final day of the Titration Period. Lacosamide dose (or 
matching placebo) will remain stable throughout the Maintenance Period. Subjects who complete 
the Maintenance Period and plan to participate in the open-label extension study (EP0034) will 
enter the blinded Transition Period. Subjects who require a change in dose during the 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 12 of 96
Maintenance Period will be withdrawn and enter the blinded Taper Period. Subjects who choose 
not to participate in EP0034 will also enter the Taper Period.
Subjects who complete the Maintenance Period and plan to participate in the open-label 
extension study (EP0034) will enter a 4-week blinded Transition Period. Subjects randomized to 
LCM will maintain their Maintenance Period dose during the Transition Period. Subjects 
randomized to placebo will transition to LCM in a double-blind fashion in accordance with the 
schedule provided in Table 7-4 of the protocol. 
The blinded Taper Period (2 to 4 weeks, depending on dose level achieved) is for subjects who 
will not be entering the open-label extension study (EP0034) for any of the following reasons:

Subject does not complete the Titration Period, the Maintenance Period, or the Transition 
Period

Subject does not choose to enroll in the open-label extension study (EP0034) after 
completing the Maintenance Period or the Transition Period
Taper of LCM may not be required for some subjects who discontinue study medication 
prematurely, depending on the treatment option selected by the investigator in consultation with 
the subject and/or parent/legal representative.
The dosing of study medication for the Taper Period is provided in Table 7-5 of the protocol .
There will be a 30-day Safety Follow-Up Period for subjects not entering the open-label 
extension study (EP0034).
Unscheduled visits can be conducted at the discretion of the investigator.
Each subject’s total duration of study medication administration is up to 24 weeks. The total 
study duration can be up to 36 weeks, including the 30-day safety Follow-Up Period.
Detailed tabular schedules of study procedures and a study schematic diagram are included in 
sections 5.2 and 5.3 of the protocol, respectively.
2.4
Determination of sample size
Assuming an effect size of 0.342, in which the effect size was calculated using a placebo-
subtracted difference of -0.249 and a common SD of 0.73 on the log-transformed data, the 
difference of -0.249 on the log-transformed data is equivalent to approximately 22% reduction 
over placebo after exponentiation. With this effect size, power of 80%, and a 2-sided test at the 
5% level of significance, a sample of 135 subjects in each treatment arm will be needed.
Assuming a responder rate of 22% and 40% for the placebo and LCM groups, respectively, a 2-
sided continuity corrected Chi-square test at a significance level of 5% will provide 
approximately 87% power with 135 subjects in the placebo group and 135 subjects in the LCM 
group.
To account for an anticipated subject dropout rate of approximately 14%, the planned number of 
subjects to enroll is 154 subjects per treatment arm.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 13 of 96
2.4.1
Blinded sample size re-estimation procedure
After 50% of subjects have been randomized, completed the study (including those who 
discontinued), and have Baseline and post-Baseline seizure data available for analysis, a sample 
size re-estimation procedure will be performed in 2 consecutive stages of adjustment:

Stage 1: Initial sample size re-estimation. An initial sample size re-estimation with equal 
allocation in each treatment arm will be performed using the related residual variance 
combined with Guenther adjustment (Friede and Kieser, 2011) to give a revised sample size 
to be adjusted in Stage 2 and Stage 3. This value will not be adjusted by more than 10% 
above the current estimate of 135 subjects per treatment arm (ie, the initial sample size 
re-estimate will not be adjusted above 149 subjects per treatment arm).

Stage 2: Adjustment for drop-out rate. The overall study drop-out rate will be determined. 
The current SP0969 protocol plans for a 14% overall study drop-out rate for use in 
determination of sample size. If the actual overall study drop-out rate is >14%, UCB plans to 
adjust the sample size from Stage 1 accordingly, using an overall study drop-out rate up to a 
maximum of 24% (ie, the original estimated overall study drop-out rate can be increased by a 
maximum of 10%). 
3
DATA ANALYSIS CONSIDERATIONS
3.1
General presentation of summaries and analyses
Statistical analysis and generation of tables, figures, subject data listings, and statistical output 
will be performed using SAS Version 9.3. All tables and listings will use Courier New font     
size 9.
Descriptive statistics will be displayed to provide an overview of the study results. For 
categorical parameters, the number and percentage of subjects in each category will be 
presented. The denominator for percentages will be based on the number of subjects appropriate 
for the purpose of 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 subjects (n), mean, standard deviation (SD), median, minimum, and maximum.
Decimal places for descriptive statistics will always apply the following rules:
•
“n” will be an integer.
•
Mean, SD, and median will use 1 additional decimal place compared to the original data.
•
Coefficient of variance (CV[%]) will be presented with 1 decimal place.
•
Minimum and maximum will have the same number of decimal places as the original value.
Statistical tests of efficacy variables will be presented as 2-sided p-values rounded to 4 decimal 
places. P-values less than 0.0001 will be presented as “<0.0001” and p-values greater than 
0.9999 will be presented as “>0.9999.” Statistical comparison will be performed at the 0.0500 
level of significance.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 14 of 96
A complete set of data listings containing all documented data and all calculated data (eg, change 
from Baseline) will be generated, and will be sorted by site, subject number and visit (where 
applicable).
3.2
General study level definitions
3.2.1
Analysis time points
3.2.1.1
Last dose of study medication
Unless otherwise noted, all references to the last dose of study medication in this SAP refer to
the last dose of study medication taken across all study periods (ie, the last dose of study 
medication across the Titration, Maintenance, Transition, and Taper Periods). The last dose of 
study medication during the Treatment Period will be defined as the last dose during the 
Titration and Maintenance Periods.
3.2.1.2
Relative day
Relative day will be calculated as the current date minus the date of first dose of study 
medication plus 1 for days on or after the day of first dose of study medication and prior to or on 
the day of last study medication dose (eg, the day of first dose will be Day 1.) Relative day will 
be calculated as the current date minus the date of first dose of study medication for days prior to 
the first dose of study medication (the day prior to first dose will be Day -1). For days after the 
last dose of study medication, relative day will be calculated as the current date minus the date of 
last dose of study medication 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 or missing dates.
3.2.2
Study periods
The study consists of the following six periods: Baseline Period, Titration Period, Maintenance 
Period, Transition Period, Taper Period, and Safety Follow-Up Period. Additionally for analysis 
purposes, the Treatment Period includes Titration and Maintenance Periods. Each period is 
defined in turn as follows for the classification by study period:
Baseline Period
On or after the date of Visit 1 (entry to study) and prior to the date of first dose of study 
medication.
Titration Period
On or after the date of first dose of study medication and prior to or on the end date of the 
Titration Period (Visit 5) for subjects who complete the Titration Period, or on or after the date 
of first dose of study medication and prior to or on the date of the Early Termination Visit (ETV) 
for subjects who discontinue during the Titration Period. If a subject does not have a 
Visit 5/ETV, then either the date of the last scheduled or unscheduled visit during the Titration 
Period or the date of last known dose of study medication during the Titration Period, whichever 
is later, will define the end date of the Titration Period.
Maintenance Period
The day after the end of the Titration Period (Visit 5) and prior to or on the end date of the 
Maintenance Period (Visit 8) for subjects who complete the Maintenance Period, or the day after 
the end of the Titration Period (Visit 5) and prior to or on the date of the ETV for subjects who 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 15 of 96
discontinue during the Maintenance Period. If a subject does not have a Visit 8/ETV, then either 
the date of the last scheduled or unscheduled visit during the Maintenance Period or the date of 
last known dose of study medication during the Maintenance Period, whichever is later, will 
define the end date of the Maintenance Period.
Treatment Period
On or after the date of first dose of study medication and prior to or on the end date of the 
Treatment Period (Visit 8) for subjects who complete the Treatment Period, or on or after the 
date of first dose of study medication and prior to or on the date of the ETV for subjects who 
discontinue during the Treatment Period. If a subject does not have a Visit 8/ETV, then either the 
date of the last scheduled or unscheduled visit during the Treatment Period or the date of last 
known dose of study medication during the Treatment Period, whichever is later, will define the 
end date of the Treatment Period.
Transition Period
For those subjects who complete the Maintenance Period and plan to participate in the open-label 
extension study (EP0034), the Transition Period is defined as the date after the last dose of study
medication in the Maintenance Period and prior to enrollment into EP0034.
Taper Period
For those subjects who discontinue study medication or for those subjects who complete the 
Maintenance Period but choose not to enter EP0034, the Taper Period is defined as the date after 
the last dose of study medication in the Titration, Maintenance or Transition Periods, as 
appropriate, and the date of last dose of study medication.
Safety Follow-Up Period
There will be a 30-day Safety Follow-Up Period for subjects not entering EP0034. The Safety 
Follow-Up Period is defined as the date after the last dose of study medication in SP0969 and 
continues until the date of last telephone contact and/or 30 days after the last dose of study 
medication, whichever is later.
3.2.3
Mapping of assessments performed at Early Termination Visit
Efficacy and safety assessments at an ETV that correspond to a scheduled visit will be 
summarized at the scheduled visit corresponding to the ETV if the assessment was scheduled to 
occur at that visit. 
In particular, clinical laboratory parameters, vital signs, and body weight are assessed at all visits 
during the Treatment Period, and so all assessments of these variables at ETVs corresponding to 
a scheduled visit will be mapped to the corresponding scheduled visit.
3.2.4
Last Visit
The Last Visit for all assessments is the last non-missing assessment during the Treatment 
Period. All scheduled and unscheduled assessments within this time period will be considered. 
Last Visit will be determined separately for each study procedure where Last Visit is mentioned 
within this document.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 16 of 96
3.3
Definition of Baseline values
In general, Baseline values for efficacy and safety variables will be determined from the last non-
missing scheduled or unscheduled assessment prior to the first dose of study medication, unless 
otherwise noted for a specific type of data.
3.4
Protocol deviations
Important protocol deviations are deviations from the protocol which could potentially have a 
meaningful impact on either the primary efficacy outcome or key safety outcomes for an 
individual subject. The criteria for identifying important protocol deviations and the 
classification of important protocol deviations will be defined separately in an important protocol 
deviations document. To the extent feasible, rules for identifying protocol deviations will be 
defined without review of the data and without consideration of the frequency of occurrence of 
such deviations. Whenever possible, criteria for identifying important protocol deviations will be 
implemented algorithmically to ensure consistency in the classification of important protocol 
deviations across all subjects.
In general, protocol deviations will be considered according to the following general categories:

Inclusion criteria

Exclusion criteria

Withdrawal criteria

Prohibited concomitant medications

LCM dosing regimen

Procedural non-compliance
Important protocol deviations will be reviewed as part of the blinded Data Evaluation Meetings
(DEMs) prior to unblinding of the database. A list of subjects with important protocol deviations 
will be agreed upon during the DEMs and will be documented in the DEM minutes. 
3.5
Analysis sets
The analysis sets defined for this study are the Safety Set (SS), Full Analysis Set (FAS), Per 
Protocol Set (PPS), and Pharmacokinetic Per Protocol Set (PK-PPS).
The primary analysis for the efficacy data will be the FAS. The secondary analysis set for the 
efficacy data will be the PPS. The primary analysis set for the safety parameters is the SS. The 
primary analysis set for the PK parameters is the PK-PPS.
3.5.1
Safety Set
The SS will include all randomized subjects who took at least 1 dose of study medication.
3.5.2
Full Analysis Set
The FAS will include all subjects who were randomized, received at least 1 dose of study
medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 17 of 96
3.5.3
Per Protocol Set
The PPS includes all subjects in the FAS who did not have important protocol deviations
considered to have an impact on efficacy as confirmed during a DEM conducted prior to study 
unblinding.
3.5.4
Pharmacokinetic Per Protocol Set
The PK-PPS will consist of all subjects having provided at least 1 measurable post-dose plasma 
sample (with recorded sampling time) on at least 1 visit with documented study medication 
intake times. 
3.6
Treatment assignment and treatment groups
It is expected that subjects will receive treatment as randomized. Thus, treatment assignment for 
the FAS and the SS will be according to randomization. However, if after unblinding it is 
determined that the subjects received treatment other than what they were randomized to receive, 
the safety analyses will be conducted using treatment assignments according to the actual 
treatment received (SS-as treated).
All subjects treated in this study receive study LCM at doses ranging from 8mg/kg/day to 
12mg/kg/day (oral solution) for subjects weighing <30kg, 6mg/kg/day to 8mg/kg/day (oral 
solution) for subjects weighing ≥30kg to <50kg, 300mg/day to 400mg/day (tablets) for subjects 
weighing  ≥50kg, or matching placebo. The subject’s body weight at Baseline (Visit 2) will be 
used to determine dose throughout the study. Summaries will be presented based on treatment 
group; Placebo and LCM, and will generally not be differentiated by LCM dose. Where 
appropriate, LCM dose will be presented in subject data listings.
3.7
Center pooling strategy
All centers will be pooled by country for the purpose of analysis.
3.8
Coding dictionaries
Medical history and AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA® v16.1). Medications will be coded using the World Health Organization Drug 
Dictionary (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.
4
STATISTICAL/ANALYTICAL ISSUES
4.1
Adjustments for covariates
An analysis of the primary efficacy variable and analyses of several other efficacy variables will 
be adjusted for Baseline seizure frequency and pooled center.
4.2
Handling of dropouts or missing data
4.2.1
Missing data
For subjects who discontinue prior to the Maintenance Period, all available seizure frequency 
data will be carried forward from the Titration Period for the Maintenance Period analysis. For 
subjects who prematurely discontinue during the Maintenance Period, all available seizure 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 18 of 96
frequency data in the Maintenance Period will be carried forward for the entire Maintenance 
Period. 
Subjects who discontinue prior to any efficacy data collection will not be included in the analysis 
(ie, data will not be carried forward from Baseline). The imputation for the seizure frequency 
data will not carry forward into the Transition and Taper Periods.
No imputation of missing values associated with an individual date or visit is planned for the 
primary safety analysis, with the exception of partial date information for AEs and concomitant 
medications in order to determine whether the AEs are treatment-emergent or the medications
are concomitant.   
With respect to AEs, events with missing intensity will be assumed to be severe. Events with 
missing relationship to study medication per the investigator will be assumed to be related. 
Incomplete or missing dates for events will be handled as described in section 3.2.2.
4.2.2
Incomplete dates for adverse events and concomitant medications
For analyses of AEs and concomitant medication usage, a complete date must be established in 
order to correctly identify the AE or medication as occurring during treatment or not. For 
purposes of imputing missing components of partially-reported start and stop dates for AEs and 
for medication use, the algorithms listed below will be followed. Start and stop dates of AEs or 
concomitant medication will be displayed as reported in the subject data listings (ie, no imputed 
values will be displayed in data listings).

Missing start day, but month and year present:
If the start of study medication occurred in the same month and year as the occurrence of 
the AE/concomitant medication, the start day of the event/concomitant medication will be 
assigned to the day of first intake of study medication. Otherwise the start day will be set 
to the 1st day of the month.

Missing start day and month, but year present:
If the start of study medication occurred in the same year as the occurrence of the 
AE/concomitant medication, the start day and month will be assigned to the date of first 
intake of study medication. Otherwise the start day and month will be set to January 1st.

Missing end day, but month and year present:
The end day will be set to the last day of the month.

Missing end day and month, but year present:
The end day and month will be set to the maximum of the date of study termination or the 
date equivalent to 28 days after last intake of study medication. 
However, if the study termination year and year for the date which is 28 days after last intake of 
study medication are greater than the event/concomitant medication year, the day and month are 
to be set to December 31st.
4.2.3
Definition of concomitant medication in case of missing dates
With respect to definition of medication as concomitant, the following rule will be applied in 
case of completely missing stop and/or start date information: 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 19 of 96
Medications, excluding AEDs, with a missing start date whose stop date is either unknown or 
after the date of the first dose of study medication will be considered as concomitant medication. 
AEDs with a missing start date whose stop date is unknown will be considered as lifetime AEDs. 
AEDs with a missing start date whose stop date is after the date of first dose of study medication 
will be considered concomitant.
Medications, including AEDS, with a missing start date whose stop date is prior to first intake of 
study medication will not be considered concomitant.
In subject data listings, dates will be displayed as reported.
4.2.4
Incomplete dates for the last administration of study medication
For purposes of imputing missing components of partially reported dates for the last 
administration of study medication, the algorithms listed below will be followed. Stop dates of 
study medication will be displayed as reported in the subject data listings (ie, no imputed values 
will be displayed in data listing).

Missing last administration day, but month and year present:
The last administration day will be set to the last day of the month or the date of the final 
contact, whichever is earlier in the month.

Missing last administration day and month, but year present:
The last administration day will be set to the last day of the year or the date of the final 
contact, whichever is earlier in the year.

Completely missing date of last administration:
For calculating the duration of exposure, if the date of last administration is completely 
missing and no information could be obtained from data cleaning exercises, the date of 
last administration should be imputed as the date of last contact according to the Study 
Termination eCRF module. For all other purposes, no imputation will be done if the date 
of last administration is completely missing.
If a subject died during the study, and the imputed last administration date according to the rules 
above is after the date of death, the last administration date will be assigned to the date of death.
4.2.5
Incomplete dates for seizure diary data
Seizure frequency and seizure-free days will be calculated over non-missing diary days during 
each time interval; days for which seizure diary data were not obtained will not be considered in 
the calculation of seizure frequency or seizure-free days. If more than 10% of the diary entries 
are missing for a specific subject and time interval, then that subject will not be considered for 
the calculation of seizure frequency or seizure-free days during that time interval.
4.2.6
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:

Start and stop dates of AEs
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 20 of 96

Start and stop dates of concomitant medication

Start and stop dates of study medication

Start and stop dates of seizure diary data
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 informal interim analysis for determination of efficacy is planned for this study. To ensure 
subject safety, interim reviews of the safety data will be performed using an Independent Data 
monitoring Committee (IDMC). Serious adverse events and other significant events (detailed in
Appendix 12 (section 12.2) are monitored and will be triaged by the medical monitor and UCB 
Drug Safety in real time. After this triage, events will be passed on to the IDMC as appropriate. 
In addition, 3 interim reviews of safety data by the IDMC are planned when 25%, 50%, and 75% 
of subjects have been randomized and at study completion. Study enrollment will not be halted 
during planned IDMC review of the safety data. The objective, procedures, and timing of the 
IDMC safety assessments to evaluate risk and benefit for subjects in SP0969 will be described in 
the IDMC Charter.   
A blinded sample size re-estimation will be performed when 50% of subjects have been 
randomized, completed the study (including those who discontinued), and have Baseline and 
post-Baseline seizure data available for analysis. See section 2.4.1 for details. 
4.4
Multicenter studies
This is a multicenter study. It is planned to appropriately pool centers by geographic location. 
The final strategy for pooling will be determined at the final DEM prior to unblinding the study. 
Treatment by center interactions will be explored in the analysis.
4.5
Multiple comparisons/multiplicity
There will be no adjustment for multiplicity in this study.
4.6
Use of an efficacy subset of subjects
The primary efficacy variable will also be analyzed for the PPS. This analysis set will provide 
additional information on the analysis of the primary efficacy variable and the impact of the 
important protocol deviations on efficacy. 
Other than the planned analyses based on the PPS, no other efficacy subsets are defined for 
statistical analyses.
4.7
Active-control studies intended to show equivalence
This section is not applicable for this study.
4.8
Examination of subgroups
Age at enrollment will be categorized into the subgroups: ≥4 to <12 years, and ≥12 to <17 years 
and used within summaries of disposition, demography, exposure, adverse events and certain 
efficacy analyses. Weight at Baseline will be categorized into the subgroups: <30kg, ≥30kg to 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 21 of 96
<50kg, and ≥50kg, and used within summaries of exposure and adverse events. Further detail of 
these summaries is provided within the relevant subsections of sections 8 and 10.
Separate age subgroupings are used for the purpose of PedsQL summaries, and are detailed in 
section 8.3.3.
5
STUDY POPULATION CHARACTERISTICS
5.1
Subject disposition
The number of subjects screened, and the number and percentage of those subjects who were 
screen failures, broken down by primary reason for screening failure will be presented overall 
and repeated by age group, using the levels defined in section 4.8.
An overall summary of disposition for the SS will present the number and percentage of subjects 
randomized in the study, subjects completing the study, and subjects discontinuing along with 
the reason for discontinuation by treatment group and overall. This will be repeated for subjects 
in the FAS and also repeated by treatment group and age group for the SS.
In addition, an overall summary of disposition for the SS, as described above, will be broken 
down by study period (Titration, Maintenance, Transition and Taper Periods), treatment group 
and overall.
The date of first subject in, date of last subject out, number of enrolled subjects, and the number 
of subjects randomized, number of subjects in each treatment group, and overall, and the number 
of subjects in each analysis set (SS, FAS, PPS and PK-PPS), will be summarized overall and by 
investigator site. Subjects who transferred sites will be summarized according to their original 
site. 
A summary of discontinuations due to AEs for all screened subjects will present the number and 
percentage of subjects who discontinued this study due to AEs broken down by type of AE.
The number and percentage of subjects enrolled under each protocol amendment (estimated by 
date of informed consent) will be presented. This will also be presented in the subjects data 
listings.
5.2
Protocol deviations
Important protocol deviations defined in the important protocol deviation document, and 
additionally identified at the DEMs before unblinding of the database will be listed. In addition, 
the number and percentage of subjects with at least 1 important protocol deviation will be 
summarized overall and by category of important protocol deviation for the SS. The number and 
percentage of subjects with no important protocol deviations will also be summarized for the SS.
6
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS
6.1
Demographics and other Baseline characteristics
For subjects who only have a year of birth reported based on region-specific regulations, age will 
be obtained from the Interactive Voice Response System (IVRS) used to randomize subjects. 
Otherwise, age will be calculated relative to the date of informed consent. Weight will be 
summarized from Visit 1.
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were 
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6


UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 22 of 96
Body mass index (BMI) will be calculated using the subject weight recorded at Visit 1 (at study 
entry) as:
BMI = weight in kilograms / (height in meters)2
Age, age category (≥4 to <12, and ≥12 to <17 years of age), EudraCT age category (≥24 months 
to <12 years, and ≥12 to <18 years), gender, weight (kg), weight band (<30,  ≥30 to <50, ≥50 
kg), height (cm), BMI (kg/m2), racial group (American Indian/Alaskan Native, Asian, Black, 
Native Hawaiian or Other Pacific Islander, White, and Other/Mixed), ethnicity (Hispanic or 
Latino, and not Hispanic or Latino), and vagus nerve stimulation (VNS) use (Active VNS, No 
VNS, and VNS not active) will be summarized by treatment group and overall for the SS, and 
repeated by treatment group and age group, using the levels defined in section 4.8.
A listing of reproductive potential and birth control measures for female subjects will be 
provided. No summaries of these findings are planned. 
6.2
Medical history and concomitant diseases
6.2.1
Medical history
The number and percentage of subjects with a medical history condition, including both resolved 
and ongoing conditions at the time of study entry, will be summarized overall and by MedDRA®
primary system organ class (SOC) and preferred term (PT) by treatment group for the SS.
Subjects who had any procedures of surgeries prior to study entry will be listed.
6.2.2
Concomitant diseases and conditions
The number and percentage of subjects with concomitant diseases and conditions (medical 
history conditions noted as ongoing at study entry) will be summarized by SOC and PT for 
subjects in each treatment group for the SS.
6.3
History of epilepsy
6.3.1
History of seizure types
The number and percentage of subjects experiencing each seizure type (partial-onset seizures, 
generalized seizures, and unclassified epileptic seizures) at any time prior to study entry will be 
summarized by treatment group for the SS based on the ILAE Seizure Classification History 
eCRF. 
A subject will be classified as having a history of partial-onset seizures if the subject has a 
history of simple partial (IA), complex partial (IB), or partial evolving to secondarily generalized 
(IC) seizures. A subject will be classified as having a history of generalized seizures if the 
subject has a history of absence (IIA1), atypical absence (IIA2), myoclonic (IIB), clonic (IIC), 
tonic (IID), tonic-clonic (IIE), and atonic (IIF) seizures.  
6.3.2
History of seizure characteristics
History of epileptic seizures, including the number and percentage of subjects with a history of 
withdrawal seizures, number and percentage with a history of status epilepticus, and with 
quantitative summaries of epilepsy duration and age at diagnosis will be summarized by 
treatment group for the SS.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 23 of 96
The date of first diagnosis collected in the eCRF only includes month and year; the 1st of the 
month will be imputed for calculating epilepsy duration. The age at first diagnosis will be 
imputed using the 1st of the month or the subject’s date of birth, whichever is later, if only the 
month and year are known, or January 1 of the same year or the subject’s date of birth, 
whichever is later, if only the year is known.
6.3.3
Historical seizure count
The historical seizure count eCRF records the number of seizures per pre-selected ILAE seizure 
code experienced by the subject during the 8 weeks prior to Baseline. These data will be 
provided in a subject data listing. 
6.4
Prior and concomitant medications
A listing of all medications taken during the study will be presented.
Medications will be attributed to the study periods as defined in section 3.2.2 based on the start 
date of the medication.
6.4.1
Number of Lifetime AEDs 
The number of lifetime AEDs defined as AEDs taken and stopped >28 days prior to Visit 1 (ie, 
prior to entry into the Baseline Period), or AEDs with a missing start date and unknown stop 
date, will be summarized by treatment group and overall for the SS based on the following 
categorization: 0 AEDs, 1 to 3 AEDs, 4-6 AEDs, and ≥7 AEDs.
6.4.2
Number of AEDs taken prior to the Baseline Period
The number of AEDs taken prior to the Baseline Period defined as AEDs with a start date prior 
to the date of informed consent, ie, prior to entry into the Baseline Period, excluding lifetime 
AEDs, will be summarized by treatment group and overall for the SS based on the following 
categorization: 1 AED, 2 AEDs, and 3 AEDs. 
The number and percentage of subjects taking AEDs prior to the Baseline Period will be 
summarized by WHODD chemical subgroup (Level 4) and preferred drug name, and by 
treatment group and overall for the SS. 
6.4.3
AEDs taken during the Baseline Period
The number and percentage of subjects taking AEDs during the Baseline Period defined as 
AEDs with a start date on or after the date of informed consent and prior to the first dose of study 
medication, and AEDs with a start date prior to the date of informed consent and with a stop date 
on or after the start of the Baseline Period, will be summarized, separately, by WHODD 
chemical subgroup (Level 4) and preferred drug name, and by treatment group and overall for 
the SS. 
6.4.4
Number of AEDs taken on day of first dose of study medication
The number of AEDs taken on the day of first dose of study medication will be summarized by 
treatment group and overall for the SS based on the following categorization: 1 AED, 2 AEDs, 
and 3 AEDs. 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 24 of 96
6.4.5
Concomitant AEDs
The number and percentage of subjects taking concomitant AEDs defined as AEDs taken 
concomitantly for at least one day in common with study medication will be summarized, 
separately, by WHODD chemical subgroup (Level 4) and preferred drug name, and by treatment 
group and overall for the SS.
Vagus nerve stimulation is allowed and will not be counted as a concomitant AED.
6.4.6
Non-AEDs taken prior to the Baseline Period
The number and percentage of subjects taking non-AEDs prior to the Baseline Period defined as 
medications with a start date prior to the date of informed consent, ie, prior to entry into the 
Baseline Period, will be summarized by WHODD anatomical main group (Level 1) and 
therapeutic subgroup (Level 2), and by treatment group and overall for the SS. 
6.4.7
Non-AEDs taken during the Baseline Period
The number and percentage of subjects taking  non-AEDs during the Baseline Period defined as 
medications with a start date on or after the date of informed consent and prior to the first dose of 
study medication, and medications with a start date prior to the date of informed consent and 
with a stop date on or after the start of the Baseline Period, will be summarized by WHODD 
anatomical main group (Level 1) and therapeutic subgroup (Level 2), and by treatment group and 
overall for the SS.
6.4.8
Concomitant Non-AEDs
The number and percentage of subjects taking  concomitant non-AEDs defined as medications 
taken concomitantly for at least one day in common with study medication will be summarized 
by WHODD anatomical main group (Level 1) and therapeutic subgroup (Level 2), and by 
treatment group and overall for the SS.
7
MEASUREMENTS OF TREATMENT COMPLIANCE
The total weight of used oral solution (mg) will be calculated as:
(Sum of actual weight of used oral solution [g] / 1.1g/mL) x 10mg/mL
Note that the estimated weight of 1mL of oral solution is 1.1g, and the concentration is 
10mg/mL.
Where:
Actual weight of used oral solution (g) = Total weight of bottles (including adaptors and 
caps) at Dispensation - Total weight of bottles (including adaptors and caps) at Return
The expected weight of used oral solution (mg) will be calculated as:
Sum of daily oral solution (mg) for each day in the corresponding time period
Where: 
Daily oral solution (mg) = (Morning dose [mg/kg] + Evening dose [mg/kg])  x Baseline 
weight (kg)
Total amount of tablets (mg) will be calculated as:
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 25 of 96
(100 x [number of 100 mg tablets dispensed – number of 100 mg tablets returned] + 50 x 
[number of 50 mg tablets dispensed – number of 50 mg tablets returned])
Expected amount of tablets (mg) will be calculated as:
Sum of daily tablets (mg) for each day in the corresponding time period
Where: 
Daily tablets (mg) = Morning dose (mg) + Evening dose (mg)
Compliance
Compliance during a time period will be calculated using data from the respective time period 
only as follows:
100 x (Total weight of used oral solution [mg] + Total amount of tablets used [mg]) / (expected 
weight of used oral solution [mg] + expected amount of tablets [mg])
A subject’s dosing compliance should be within 75-125% during each visit. Compliance to study 
medication dosing will be calculated for each visit, and will also be determined for the Titration 
Period, Maintenance Period, and the entire Treatment Period (Titration+Maintenance Periods).
Compliance will be summarized separately for the Titration Period, Maintenance Period, and 
entire Treatment Period for the SS. It will be presented using descriptive statistics and 
additionally using the categorization <75%, ≥75% to ≤125%, and >125%.
8
EFFICACY ANALYSES
The primary and secondary efficacy variables will be measured using data obtained from the 
subject diary. Subjects or parents/caregivers will keep a diary to record the daily seizure activity 
from the beginning of the Baseline Period until the last visit, recording both seizure type, seizure 
frequency, and whether the seizures were a cluster.
Each seizure code in the clinical database will be mapped to exactly 1 of the ILAE seizure codes 
based on the 1981 ILAE classification (Seizure Count eCRF).
The assessment of efficacy is based on seizure frequency, and will be analyzed primarily for the 
FAS. All CIs presented will be 95% 2-sided CIs.
For subjects who prematurely discontinue from the study, last observation carried forward 
method as described in section 4.2 will be applied to obtain a seizure frequency estimate for the 
Maintenance Period. 
All efficacy variables will be listed.
8.1
Statistical analysis of the primary efficacy variable
8.1.1
Derivations of primary efficacy variable
The primary efficacy variable is the change in partial-onset seizure frequency per 28 days from 
Baseline to the Maintenance Period. Seizure frequency per 28 days will be based on the number 
of days for which seizure information was provided during the specified time interval.
Seizure frequency per 28 days will be calculated as ([number of seizures over the specified time 
interval] divided by [number of days in the interval]) multiplied by 28.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 26 of 96
The partial-onset seizure frequency per 28 days will be calculated for both the Baseline Period 
and for the Maintenance Period, and the change from Baseline calculated. 
If a seizure cluster is reported, the highest recorded daily seizure frequency during the Treatment 
Period for the seizure type associated with the report of a seizure cluster will be used as the 
imputed seizure frequency for the day on which the cluster occurred.
8.1.2
Primary analysis of the primary efficacy variable
Seizure frequency will be analyzed using analysis of covariance (ANCOVA) with terms for 
treatment and center (pooled appropriately), on log-transformed seizure frequency using the 
transformation of ln(X+1), where X is the seizure frequency. Log transformed Baseline seizure 
frequency will be used as a covariate. Assumptions for the parametric model will be evaluated by 
diagnostic (eg, Shapiro-Wilk test for normality) and graphical methods such as residual plots, 
including normal probability plots, histograms, and plots of residuals versus Baseline covariate 
values and treatment. An assessment will be made with regards to the influence of individual 
observations (eg, extreme outliers) on the analysis. To the extent feasible, such potential 
influential observations will be identified prior to unblinding, and an assessment will be made 
with regard to the potential impact of such data, including the evaluation of alternative statistical 
methodology such as non-parametric methods. If deemed that a non-parametric method is 
warranted, an ANCOVA model on rank of seizure frequency per 28 days with terms for 
treatment and center (pooled appropriately) will be employed as the primary analysis. Ranked
seizure frequency per 28 days during the Baseline Period will be used as a covariate. 
The seizure frequency between treatment and placebo will be compared using the least squares 
means (LSMs). The percent reduction over placebo will be estimated as 100 x (1 – exp [LSM 
LCM – LSM placebo]). A 95% CI will also be calculated for the percent reduction over placebo. 
Partial-onset seizure frequency per 28 days during the Baseline Period and during the 
Maintenance Period, and the change from Baseline will be summarized by treatment group. This 
summary will be repeated by treatment group and age group, using the levels defined in section 
4.8.
8.1.3
Secondary analyses of the primary efficacy variable
The primary analysis of the primary efficacy variable described in section 8.1.2 will be repeated 
for the PPS.
8.1.4
Supportive and sensitivity analyses of the primary efficacy variable
The impact of missing data on the primary efficacy analysis will be evaluated by repeating the 
primary analysis of the primary efficacy variable detailed in section 8.1.2 on observed cases.
For subjects who prematurely discontinue from the study, only data recorded up to their ETV 
will be used to obtain a partial-onset seizure frequency estimate for the Maintenance Period. 
8.2
Statistical analysis of the secondary efficacy variables
The secondary efficacy variables will be summarized and/or analyzed for the FAS.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 27 of 96
8.2.1
Change in partial-onset seizure frequency per 28 days from Baseline 
to entire Treatment Period
The partial-onset seizure frequency per 28 days will be calculated for both the Baseline Period 
and for the entire Treatment Period, as detailed in section 8.1.1. The change from Baseline will 
also be calculated.
The change in partial-onset seizure frequency per 28 days from Baseline to the entire Treatment 
Period will be analyzed as detailed in section 8.1.2.
Partial-onset seizure frequency per 28 days during the Baseline Period and during the entire 
Treatment Period, and change from Baseline will be summarized by treatment group. This 
summary will be repeated by treatment group and age group, using the levels defined in      
section 4.8.
The change in seizure frequency per 28 days from Baseline to the Treatment Period, defined as 
the combined Titration and Maintenance Periods, will be summarized by treatment group (LCM 
or placebo) using descriptive statistics. Statistical testing will be performed using an ANCOVA 
model with terms for treatment and pooled site and baseline seizure frequency as a covariate.
The change in seizure frequency by period will also be summarized using descriptive statistics 
by treatment group and seizure type.
The change in seizure frequency by visit will also be summarized, based on observed analysis. 
For each visit during the Titration Period, the LCM treatment group will be compared to placebo 
in an exploratory onset of efficacy analysis. Statistical testing will be performed using an 
ANCOVA model with terms for treatment and pooled site and baseline seizure frequency as a 
covariate using data recorded at each individual Titration Period visit.
8.2.2
Proportion of responders, where a responder is a subject 
experiencing a 50% or greater reduction in partial-onset seizure 
frequency from Baseline to end of Maintenance Period
The secondary efficacy variable is the proportion of responders, where a responder is a subject 
experiencing a 50% or greater reduction in partial-onset seizure frequency from Baseline to the 
end of Maintenance Period.
Percent reduction will be calculated as ([absolute reduction in partial-onset seizure frequency] 
divided by [Baseline partial-onset seizure frequency]) multiplied by 100.
Absolute reduction in partial-onset seizure frequency is calculated as (Baseline partial-onset 
seizure frequency) minus (Maintenance Period partial-onset seizure frequency).
The subject is considered a responder if the data shows a 50% or greater reduction in partial-
onset seizure frequency from Baseline to end of Maintenance Period, otherwise the subject will 
be considered a non-responder.
This variable will be analyzed using a logistic regression model with terms for treatment and 
center to measure the association between the response variable and treatment after controlling 
for center. The odds ratio, 95% CI, and p-value associated with treatment will be presented. 
The number and percentage of responders will be summarized by treatment group.  
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 28 of 96
The response to treatment for each response level will also be summarized using descriptive 
statistics by treatment group and seizure type, with the seizure types presented as follows: simple 
partial seizures (IA), complex partial seizures (IB), partial seizures evolving to secondarily
generalized (IC), generalized seizures (II), and unclassified epileptic seizures (III). This summary 
will be repeated by treatment group and age group, using the levels defined in section 4.8.
Only subjects who experienced the respective seizure type during the Baseline Period will be 
included in the analysis for that seizure type with only the seizure frequencies of that seizure type 
being used in the analysis. Subjects can be analyzed under multiple seizure types in these 
summaries. No statistical testing will be performed for these by seizure type summaries.
8.2.3
Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or 
>75% reduction in partial-onset seizure frequency from Baseline to 
end of Maintenance Period
The proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or >75% reduction in 
partial-onset seizure frequency from Baseline to end of Maintenance Period will be summarized 
by treatment group.  
Percent reduction will be calculated as defined in section 8.2.2.
The number and percentage of subjects in each of the categories will be summarized by 
treatment group.  
8.2.4
Proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or 
>75% reduction in partial-onset seizure frequency from Baseline to 
entire Treatment Period
The secondary efficacy variable is the proportion of subjects experiencing a ≥25% to <50%, 50% 
to 75%, or >75% reduction in partial-onset seizure frequency from Baseline to the entire 
Treatment Period.
Percent reduction will be calculated as defined in section 8.2.2.
The number and percentage of subjects in each of the 3 categories will be summarized by 
treatment group.  
Additionally, the proportion of subjects experiencing a ≥25% to <50%, 50% to 75%, or >75% 
reduction in partial-onset seizure frequency from Baseline to each post-Baseline scheduled visit 
during the entire Treatment Period will be determined.
Percent reduction will be calculated as defined in section 8.2.2, with absolute reduction in 
partial-onset seizure frequency calculated as (Baseline partial-onset seizure frequency) minus 
(Visit partial-onset seizure frequency).
Each subject will be categorized into 1 of the 3 reduction in partial-onset seizure groups (≥25% 
to <50%, 50% to 75%, or >75%), at each visit.  
The number and percentage of subjects in each of the 3 categories will be summarized by 
treatment group for each post-Baseline visit.  
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 29 of 96
8.2.5
Proportion of subjects experiencing no change in partial-onset 
seizure frequency from Baseline to entire Treatment Period
The secondary efficacy variable is the proportion of subjects experiencing no change in partial-
onset seizure frequency (between <25% reduction and <25% increase) from Baseline to the 
entire Treatment Period.
Percent reduction/increase will be calculated as defined in section 8.2.2.
Each subject will be categorized into 1 of the 2 partial-onset seizure frequency groups (between 
<25% reduction and <25% increase, or not between <25% reduction and <25% increase).  
This variable will be analyzed using a logistic regression model with terms for treatment and 
center to measure the association between the response variable and treatment after controlling 
for center. The odds ratio, 95% CI, and p-value associated with treatment will be presented. 
The number and percentage of subjects in each of the 2 categories will be summarized by 
treatment group.  
8.2.6
Proportion of subjects experiencing an increase in partial-onset 
seizure frequency from Baseline to entire Treatment Period
The secondary efficacy variable is the proportion of subjects experiencing an increase in partial-
onset seizure frequency of ≥25% from Baseline to the entire Treatment Period.
Percent increase will be calculated as defined in section 8.2.2.
Each subject will be categorized in 1 of 2 increase in partial-onset seizure frequency groups 
(≥25% or <25%).
This variable will be analyzed using a logistic regression model with terms for treatment and 
center to measure the association between the response variable and treatment after controlling 
for center. The odds ratio, 95% CI, and p-value associated with treatment will be presented. 
The number and percentage of subjects in each of the 2 categories will be summarized by 
treatment group.  
8.2.7
Change in partial-onset seizure frequency per 28 days from Baseline 
to the entire Treatment Period by seizure type
The partial-onset seizure frequency per 28 days will be calculated for both the Baseline Period 
and for the entire Treatment Period, as detailed in section 8.1.1, by seizure type. The change 
from Baseline will also be calculated by seizure type.
The change in partial-onset seizure frequency per 28 days from Baseline to the entire Treatment 
Period will be analyzed as detailed in Section 8.1.2.
Partial-onset seizure frequency per 28 days during the Baseline Period and during the entire 
Treatment Period, and change from Baseline will be summarized by treatment group and seizure 
type.
In addition, descriptive statistics for change and percent change in seizure frequency per 28 days 
from Baseline to each post-Baseline visit during the entire Treatment Period will be presented by 
treatment group and seizure type. Partial-onset seizure frequency per 28 days will be presented 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 30 of 96
graphically at each visit by treatment group, and separately at each visit by seizure type and 
treatment group. 
8.2.8
Proportion of seizure-free days during Maintenance Period
For all subjects who enter the Maintenance Period, the proportion of seizure-free days during the 
Maintenance Period will be calculated.
The proportion of seizure-free days will be calculated as (days with number of seizures = 0
during the Maintenance Period) divided by (days with recorded data in the subject diary during 
the Maintenance Period), where “days with recorded data in the subject diary” excludes any days 
where “Not Done” is recorded.
Days with missing seizure diary information will be excluded from both the numerator and 
denominator for the seizure-free days calculation. 
For all subjects who complete the Maintenance Period, the proportion of seizure-free days during 
the Maintenance Period will be calculated as described above, and summarized descriptively by 
treatment group.  
Statistical testing for the proportion of seizure-free days during the Maintenance Period will be 
based on an ANCOVA model with terms for treatment and pooled site and a covariate of the 
proportion of seizure-free days during the Baseline Period. Only Subjects with efficacy data 
collected during the Maintenance Period will be included.
The proportion of seizure-free days during the Maintenance Period will also be summarized 
using descriptive statistics by treatment group and seizure type.
8.2.9
Proportion of subjects who achieved “seizure-free” status for 
subjects who completed the Maintenance Period
A subject who completed the Maintenance Period will be defined as seizure-free if the subject 
did not report any seizures during the Maintenance Period, that is, there are no diary records 
during the Maintenance Period with either a count >0 or a reported seizure code with an 
unknown or missing seizure count.
Days with missing seizure diary data will be excluded from the determination of seizure free 
status as long as the percentage of days in the Maintenance Period with missing seizure diary 
data does not exceed 20%.
The number and percentage of subjects who achieved seizure free status during the Maintenance 
Period will be presented by treatment group.
8.3
Analysis of other efficacy variables
The following efficacy variables will be summarized for the FAS.
8.3.1
Clinical Global Impression of Change
The Clinical Global Impression of Change is a 7-point categorical rating scale in which the 
investigator assesses the subject’s change from Baseline in clinical status, including an 
evaluation of seizure frequency and intensity, the occurrence of AEs, and a subject’s functional 
status. This will be assessed at Visit 8, or at ETV in case of early termination.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 31 of 96
The number and percentage of subjects by Clinical Global Impression of Change value will be 
summarized for Visit 8 and Last Visit by treatment group. The denominator for the percentage 
calculation will be based on the number of subjects with non-missing values. In addition, the 3 
improvement values (Very much improved, Much improved, and Minimally improved) grouped 
as “Improved” and the 3 worsening values (Minimally worse, Much worse, and Very much 
worse) grouped as “Worsened”, together with the “No change” group will be summarized for 
Visit 8 and Last Visit by treatment group. The denominator for the percentage calculation will be 
based on the number of subjects with non-missing values.
Clinical Global Impression of Change data will be listed.
8.3.2
Caregiver’s Global Impression of Change
The Caregiver’s Global Impression of Change is a 7-point categorical rating scale in which the 
caregiver assesses the subject’s change from Baseline in clinical status, including an evaluation 
of seizure frequency and intensity, the occurrence of AEs, and a subject’s functional status. This 
will be assessed at Visit 8, or at ETV in case of early termination.
The number and percentage of subjects by Caregiver’s Global Impression of Change value will 
be summarized for Visit 8 and Last Visit by treatment group. The denominator for the percentage 
calculation will be based on the number of subjects with non-missing values. In addition, the 3 
improvement values (Very much improved, Much improved, and Minimally improved) grouped 
as “Improved” and the 3 worsening values (Minimally worse, Much worse, and Very much 
worse) grouped as “Worsened”, together with the “No change” group will be summarized for 
Visit 8 and Last Visit by treatment group. The denominator for the percentage calculation will be 
based on the number of subjects with non-missing values.
Caregiver’s Global Impression of Change data will be listed.
8.3.3
PedsQL assessment
The PedsQL is a validated instrument that consists of generic core scales suitable for use with 
pediatric populations, including those with acute or chronic health conditions. The PedsQL will 
be administered only in countries where a translated version is available and will be completed at 
Visit 2 (Baseline), Visit 8, and at ETV in case of early termination.
PedsQL generic core scale scores will be calculated for each of the following 4 PedsQL scales: 
Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. The 
PedsQL assessment is retrospective to the prior 4 weeks, and individual items are scored using a 
5-point Likert scale (0 to 4 representing responses of: never, almost never, sometimes, often, or 
almost always). These scores of 0 to 4 will be transformed by the function: 100 – (response x 25) 
in order to generate scores of 0, 25, 50, 75, and 100 where a higher value represents a better 
HRQoL.
Each scale score is then calculated as the mean of the non-missing categorized items if 50% or 
more of the items are non-missing.    
The above algorithm will also be used to calculate an overall Total Scale Score (all scales) and 
the Psychosocial Health Summary Score (a combination of the emotional, social and school 
functioning questions) for each subject.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 32 of 96
Calculated values and change from Baseline for the total scale score, psychosocial health score 
and each of the 4 scale scores will be summarized for each visit and Last Visit by treatment 
group. Subgroup summaries by age will be performed using the age groupings for which 
different questionnaires were entered: ≥2 to ≤4 years, ≥5 to ≤7 years, ≥8 to ≤12 years, and ≥13 to 
≤18 years.
All PedsQL data will be listed. 
8.3.4
Concomitant medical procedures
Subjects who had any concomitant medical procedures during the course of the study based on 
the Concomitant Medical Procedures eCRF will be listed. These will be attributed to the study 
periods based on the date of the procedure as defined in section 3.2.2. Additionally, subjects who 
had any procedures or surgeries prior to study entry based on the Procedure History eCRF will 
also be listed.
The number of concomitant medical procedures per subject will be summarized by treatment 
group for the Baseline Period and the entire Treatment Period, separately. The number of 
concomitant medical procedures per subject will be summarized using the categories 0, 1, 2, and 
3 or more. 
8.3.5
Healthcare provider consultations
Healthcare provider consultations not foreseen by the protocol will be attributed to study periods 
as defined in section 3.2.2 based on the date of consultation.
The number of healthcare provider consultations per subject during the Baseline Period and 
during the entire Treatment Period will be summarized, separately, by treatment group. The 
number of healthcare provider consultations will be summarized using the categories 0, 1, 2, 3, 4, 
and 5 or more.
The number of healthcare provider consultations during the Baseline Period and during the 
Treatment Period, separately, will be summarized by type of provider (General Practitioner, 
Specialist Physician, Nurse, or Other) and treatment group. Percentages will be relative to the 
number of healthcare provider consultations during the Baseline Period and during the entire 
Treatment Period, respectively.
All healthcare provider consultations data will be listed.
8.3.6
Hospital stays and emergency room visits
Hospital stays and emergency room ( ER) visits will be attributed to study periods as defined in 
section 3.2.2 based on admission date.
The number of hospital stays per subject during the Baseline Period and during the entire 
Treatment Period, separately, will be summarized by treatment group. The number of hospital 
stays will be summarized using the categories 0, 1, 2, 3, 4, and 5 or more. The number and 
percentage of subjects with specific reasons for duration of hospital stays will be summarized for 
the duration of the Baseline Period and for the duration of the entire Treatment Period, 
separately, by treatment group.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 33 of 96
Duration of hospital stays will be categorized as 0 days, 1-5 days, 6-10 days, 11-15 days, and 
>15 days, and summarized for the duration of the Baseline Period and the duration of the entire 
Treatment Period, separately, by treatment group. 
An event logged on the Hospitalization/ER Visit eCRF module where ER is marked as the initial 
entry point will be defined as an ER visit. An ER visit with a subject transfer to an inpatient 
general ward will also be counted as a hospitalization. However, all other instances of ER visits 
(where subject transfer is not to an inpatient general ward) will not be counted as 
hospitalizations.  Descriptive statistics for the number of ER stays during the Baseline Period and 
for the duration of the entire Treatment Period, will be presented, separately, by treatment group. 
The number of ER visits will be summarized using the categories 0, 1, 2, and 3 or more. The
number and percentage of subjects with specific reasons for duration of ER visits will be 
summarized for the duration of the Baseline Period and the duration of the entire Treatment 
Period, separately, by treatment group.
The duration of each hospital stay will be calculated as the discharge date minus the admission 
date (Hospitalization/ER Visit Date on the eCRF) plus 1 day for hospital stays with a discharge 
date. Hospitalizations with either a partial admission or discharge date are ignored for the 
calculation of duration of hospital stay. However, such hospitalizations are counted for the 
number of hospital stays. The durations of hospital stays will be summed within each of the 
study periods defined in section 3.2.2. Subjects with no hospital stays within a study period will 
have a duration of 0 days for that period. Should distinct records for hospital stays overlap, then 
the days during the overlap will only be counted once. Similarly, this also applies for the ER 
visits.
All hospitalization/ER data will be listed.
9
PHARMACOKINETICS  
9.1
Descriptive statistics of LCM and AED plasma concentrations
The results of LCM and other AEDs plasma concentrations will be described by the method of 
descriptive statistics: arithmetic mean, SD, median, range, geometric mean, and geometric CV. 
The evaluations will be done based on separation by LCM maintenance dose level, and repeated 
by LCM maintenance dose level and age group.
Summarization of PK data relative to time after dose will be performed for the overall group and 
separated by AED therapy and possibly age groups.
9.2
Population pharmacokinetics
A population PK modeling of the LCM concentration time data will be performed within the 
NONMEM software. The effects of age, body weight, AED therapy, and other covariates will be 
evaluated. Simulations will be undertaken for estimating dose adaptations leading to the same 
exposure as in adults. 
The methods will be described in the Data Analysis Plan (DAP) and the results will be reported 
in a separate modeling report.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 34 of 96
9.3
Exposure-response
A model-based approach will be used to describe the relationship between LCM and seizure 
counts data. The PK and pharmacodynamics (PD) data will be combined and exploratory 
analyses will be conducted to determine if a dose-response relationship can be demonstrated. 
Additional information will be documented separately in a DAP.
10
SAFETY ANALYSES
The following safety variables will be summarized for the SS.
10.1
Extent of exposure
All the summaries described below will also be presented for the FAS.
The overall duration of study medication exposure during each of the Titration Period, 
Maintenance Period and entire Treatment Period (defined in section 3.2.2) will be calculated, as 
follows:
Titration Period: date of last dose of study medication during the Titration Period minus the date 
of first dose of study medication plus 1.
Maintenance Period: date of last dose of study medication during the Maintenance Period minus 
the date of first dose of study medication during the Maintenance Period plus 1.
Entire Treatment Period: date of last dose of study medication during the entire Treatment Period 
minus the date of first dose of study medication plus 1.
The overall duration of study medication exposure will be summarized for each of the study
periods defined above by treatment group, and repeated by treatment group and age group, and 
by treatment group and weight group using the levels defined in section 4.8. 
In addition, the overall duration of study medication exposure will be summarized using the 
following categories for each of the study periods defined above by treatment group, and 
repeated by treatment group and age group, and by treatment group and weight group using the 
levels defined in section 4.8:
Titration Period: ≤2 weeks, >2-≤4 weeks, and >4-≤6 weeks.
Maintenance Period: ≤2 weeks, >2-≤4 weeks, >4-≤6 weeks, >6-≤8 weeks, and >8-≤10 weeks.
Entire Treatment Period: ≤2 weeks, >2-≤4 weeks, >4-≤6 weeks, >6-≤8 weeks, >8-≤10 weeks, 
>10-≤12 weeks, >12-≤14 weeks, and >14- ≤16 weeks. 
The median total daily dose during the Titration Period, Maintenance Period, and entire 
Treatment Period will be summarized by treatment group, and repeated by treatment group and 
age group, and by treatment group and weight group using the levels defined in section 4.8. 
In addition, for the Titration Period, the number of back titration steps for each subject
(categorized as: 0, 1-3, 4-6, and ≥7), the number of subjects with a dose change together with the 
number of dose changes during the interval by dose back titration occurred (categorized as: 
<2mg/kg/day, ≥2-<4mg/kg/day, ≥4-<6mg/kg/day, ≥6-<8mg/kg/day, ≥8-<10mg/kg/day,         
≥10-≤12mg/kg/day, and >12mg/kg/day, <100mg/day, ≥100-<200mg/day, ≥200-<300mg/day, 
≥300-<400mg/day, and ≥400mg/day), the number of up titration steps for each subject
(categorized as: 0, 1-3, 4-6, and ≥7), and the number of subjects with a dose change together 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 35 of 96
with the number of dose changes during the interval by dose up titration occurred (categorized 
as: <2mg/kg/day, ≥2-<4mg/kg/day, ≥4-<6mg/kg/day, ≥6-<8mg/kg/day, ≥8-<10mg/kg/day,         
≥10-≤12mg/kg/day, and >12mg/kg/day, <100mg/day, ≥100-<200mg/day, ≥200-<300mg/day, 
≥300-≤400mg/day, and >400mg/day), will be summarized by treatment group, and repeated by 
treatment group and age group, and by treatment group and weight group using the levels 
defined in section 4.8. 
10.2
Adverse events
AEs will be tabulated by MedDRA SOC and MedDRA PT. The number and percentage of 
subjects 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.
AEs will be classified as pre-treatment, treatment-emergent, or post-treatment. Pre-treatment 
AEs are defined as AEs which had an onset date prior to the first study medication 
administration. Treatment-emergent adverse events (TEAE) are defined as those events which 
start on or after the date of first study medication administration and within 30 days following 
the date of last study medication administration, or whose severity worsens within this time 
frame. Post-treatment AEs are defined as AEs which had an onset date after 30 days after the last 
study medication administration.
All AEs reported during the study including pre-treatment and post-treatment AEs will be 
provided in a subject data listing.
An overall summary of AEs will provide the overall summary of TEAEs and the numbers and 
percentages of subjects with at least 1 TEAE, with a serious TEAE, with a TEAE that led to 
permanent withdrawal of study medication, with a drug-related TEAE, with a severe TEAE, and 
with a drug-related serious TEAE. The number and percentage of subject discontinuations due to 
TEAEs, and the number and percentage of subjects with AEs leading to death (if applicable),
will also be summarized. This overall summary will be repeated by treatment group and age 
group, and by treatment group and weight group using the levels defined in section 4.8.
The following summaries of AEs will be provided for each treatment group by MedDRA 
primary SOC and PT:

Incidence of TEAEs

Incidence of serious TEAEs

Incidence of TEAEs leading to discontinuation of study medication
All three of these summaries will then be repeated by treatment group and age group, using the 
levels defined in section 4.8. In addition, all three of these summaries will be repeated including 
the site and subject number of all those subjects experiencing each TEAE and will be presented 
by treatment group.
The incidence of TEAEs during the Titration, Maintenance, Transition, Taper, and Safety 
Follow-Up Periods, separately, will also be presented for each treatment group by MedDRA 
primary SOC and PT.   
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 36 of 96
The incidence of drug-related TEAEs by seriousness will be presented for each treatment group 
by MedDRA primary SOC and PT.
The incidence of TEAEs by dose at onset will be presented for each treatment group by
MedDRA primary SOC and PT, and will be repeated by treatment group and age group, and by 
treatment group and weight group using the levels defined in section 4.8.
The incidence of non-serious TEAEs occurring in at least 5% of subjects in any treatment group 
will be summarized for each treatment group by MedDRA primary SOC and PT, and will be 
repeated by treatment group and age group, using the levels defined in section 4.8. 
Other significant AEs, defined in Appendix 12 (section 12.2), will be summarized for each 
treatment group by MedDRA primary SOC and PT, and will be repeated by treatment group and 
weight group, using the levels defined in section 4.8. 
In addition, summaries for the incidence of TEAEs overall, incidence of serious TEAEs, 
incidence of TEAEs leading to discontinuation of study medication, and incidence of other 
significant TEAEs will be repeated presenting the site and subject number of all those subjects 
experiencing each TEAE. Subject data listings will also be presented.
10.3
Clinical laboratory evaluations
Hematology, blood chemistry (including liver function tests), urinalysis, and endocrinology
parameters are assessed throughout the study from Visit 1 (entry to study) to Visit 8, and at ETV 
in case of early termination, and may also be assessed at unscheduled visits. Laboratory 
parameters will also be assessed during the Transition Period (except endocrinology), Taper 
Period, and at the Safety Follow-Up Visit. 
Urinalysis will be performed for subjects ≥5 years of age only. All summaries of laboratory 
parameters will only summarize parameters planned based on the protocol. However, both 
planned and unplanned laboratory parameters will be provided in subject data listings. 
Summaries will include hematology, chemistry and endocrinology results; urinalysis results will 
be included in subject data listings only.
Observed values of hematology, chemistry, and non-gender specific endocrinology parameters
(ie, thyroid stimulating hormone, triiodothyronine [total and serum-free], and thyroxine [total 
and serum-free]), and change from Baseline will be summarized by treatment group for all post-
Baseline visits, and Last Visit. Gender specific endocrinology parameters (ie, follicle stimulating 
hormone, luteinizing hormone, and testosterone) will be presented similarly, by treatment group 
and gender.
Treatment-emergent markedly abnormal (TEMA) values are defined as those TEMA values 
which occur during the defined Treatment Period (see Section 3.2.2) at scheduled or unscheduled 
visits on or after the first study medication administration through to the end of the Treatment 
Period. 
The number and percentage of subjects with a TEMA value, TEMA low value, and TEMA high 
value will be summarized for each treatment group at each post-Baseline visit and Last Visit. 
Percentages will be relative to the number of subjects with a value at each visit. Criteria for 
determining if a value is TEMA are detailed in Appendix 12.1. 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 37 of 96
A serum pregnancy test will be performed on all females of childbearing potential at Visit 1 
(entry to study), Visit 4, Visit 5, Visit 7, Visit 8, and at ETV in case of early termination. A 
serum pregnancy test will also be performed during the Taper Period, and at the Safety Follow-
Up Visit, but only at the Safety Follow-Up Visit if blood is collected for other laboratory tests, 
otherwise a urine pregnancy test will be performed.
A urine pregnancy test will be performed at Visit 2 (Baseline), Visit 3, and Visit 6. A urine 
pregnancy test will also be performed at Visit 4 of the Transition Period, and at the Safety 
Follow-Up Visit, but only at the Safety Follow-Up Visit if a serum pregnancy test has not been 
performed.
A listing of serum pregnancy test results and urine pregnancy test results will be provided. No 
summaries of these results are planned. 
10.4
Vital signs, physical findings, and other observations related to 
safety
10.4.1
Vital signs, body weight, height, BMI, and head circumference
Vital signs (systolic BP [SBP], diastolic BP [DBP], and pulse rate) will be assessed after at least 
3 minutes at rest in a supine position throughout the study from Visit 1 (entry to study) to Visit 8, 
and at ETV in case of early termination, and at unscheduled visits. Vital signs will also be 
assessed during the Transition Period, Taper Period, and at the Safety Follow-Up Visit. 
Assessment of orthostatic changes will also be performed as follows: After the 3 minute 
measurement in supine position, the subject is asked to stand up, and SBP, DBP and pulse rate 
are taken approximately 1 minute and approximately 3 minutes after the subject stands up as 
feasible.
Body weight will be assessed throughout the study from Visit 1 (entry to study) to Visit 8, and at 
ETV in case of early termination, and at unscheduled visits. Body weight will also be assessed 
during the Transition Period, Taper Period, and at the Safety Follow-Up Visit. 
Height will be assessed at Visit 1 (entry to study), Visit 2 (Baseline), Visit 8, and at ETV in case 
of early termination. BMI will subsequently be calculated at these visits.  
Head circumference will be assessed at Visit 1 (entry to study), Visit 8, and at ETV in case of 
early termination.
Observed values of SBP, DBP, pulse rate, body weight, height, BMI, and head circumference
will be summarized by treatment group for each visit and Last Visit. Change from Baseline for 
SBP, DBP, pulse rate, body weight, height, BMI and head circumference will be summarized by 
treatment group for all post-Baseline visits, and Last Visit, as appropriate.
Orthostatic changes of SBP, DBP, and pulse rate will be summarized by treatment group for 
each visit and Last Visit.
Markedly abnormal (MA) values are defined as those MA values which occur during the defined 
Treatment Period (see Section 3.2.2) at scheduled or unscheduled visits on or after the first study 
medication administration through to the end of the Treatment Period. 
The number and percentage of subjects with a MA value, MA low value, and MA high value, at 
each post-Baseline visit up to Visit 8, for which SBP, DBP, pulse rate, and body weight were 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 38 of 96
scheduled to be assessed, and Last Visit, will be presented. Percentages will be relative to the 
number of subjects with a value at each visit.
The abnormal vital sign criteria are defined as follows:
Table 10‒1: Vital Signs Abnormality Criteria
Parameter
Age Range
Abnormality Criteria
Pulse Rate (beats/minute)
4y - <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)
4y - <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)
4y - <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)
4y - <12y
<15
>35
≥12y
<10
>25
Temperature
All
>101 0F (38.3 0C)
Body Weight
4y - <17y
<3% or 97% of the normal body weight 
growth curve rangesa based on gender and the 
age of subject on date of weight assessment
≥17y
≥ 10% change from Baseline (an increase or a 
decrease)
Abbreviations: m = month, y = year. A month is defined as 30 days; a year is defined as 365.25 days.
Additionally, a subject will be considered to have marked bradycardia if the pulse rate is <45bpm 
and an AE mapped to the PT bradycardia is reported for the subject. A listing of vital signs data 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 39 of 96
will be provided for all subjects with marked bradycardia. Additionally, a subject data listing of 
all vital signs for subjects with an AE mapped to the PT bradycardia will be presented. 
A subject data listing of all vital signs values including body weight, height, BMI, and head 
circumference for all subjects will be presented. A separate listing including TEMA vital signs 
values will also be presented.
10.4.2
Electrocardiograms
Standard 12-lead ECGs (2 interpretable recordings [20 to 30 minutes apart]) will be performed 
throughout the study from Visit 1 (entry to study) to Visit 8, and at ETV in case of early 
termination. Standard 12-lead ECGs will also be performed at Visit 4 of the Transition Period, at 
week 18, 19, or 20 of the Taper Period, and at the Safety Follow-Up Visit. 
Electrocardiograms will be reviewed locally and at a central ECG laboratory. If any abnormal 
finding is assessed by the investigator to be clinically significant, then the ECG should be 
repeated on the same day. If the clinically significant abnormality is confirmed by the repeat 
ECG, then the subject must be withdrawn from the study. The Investigator will determine 
whether the results of the ECG are normal or abnormal and assess the clinical significance of any 
abnormalities.
For ECGs, Baseline will be defined as the average of all pre-dose interpretable readings. For all 
post-Baseline visits, the average of all interpretable readings at the specified visit will be used for 
summaries. 
Observed values of ECG results will be summarized for each visit and Last Visit. Change from 
Baseline in ECG results will be summarized for all post-Baseline visits, and Last Visit by 
treatment group, and will be repeated by treatment group and age group, and by treatment group 
and weight group using the levels defined in section 4.8.
The number and percentage of subjects with no abnormality, an abnormal but not clinically 
significant finding, and a clinically significant finding, will be summarized by treatment group at 
Visit 1 (entry to the study), Visit 2 (Baseline), and at each post-Baseline visit up to Visit 8, and 
Last Visit. Percentages will be relative to the number of subjects with an ECG assessment at 
each time point. Subjects are counted at most once at each time point based on the worst 
observed outcome across all abnormalities reported at that time point.
Summaries of shifts from Baseline to post-Baseline visits, and from Baseline to Last Visit, will 
also be provided by treatment group based on the categories normal, abnormal, not clinically 
significant, and abnormal, clinically significant.
A listing of ECG data will be provided for all subjects with other significant TEAEs in the 
Cardiac and ECG Related Terms category defined in Appendix 12 (section 12.2). A subject data 
listing of all ECG parameter values for all subjects will also be presented. Listings will include 
results from each recording and the average of all recordings. 
The number and percentage of subjects with treatment-emergent ECG abnormalities will be 
presented by visit and treatment group. 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 Treatment Period (including unscheduled visits) 
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UCB
09 Feb 2017
Statistical Analysis Plan
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      SP0969
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and not meeting the same criteria during Baseline. All ECG parameter values will be listed for 
subjects meeting any abnormality criteria.
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 10‒2: Electrocardiogram Abnormality Criteria
Parameter
Age Range
Abnormality Criteria
QT interval (ms)
4y-<12y
>500
>12y
>500 or ≥60ms increase from Baseline
QTc(F) (ms)
4y-<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)
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)
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)
4y-<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)
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 subject data listing will be provided that identifies subjects with a clinically significant finding 
after the first dose of study medication for each type of ECG abnormality.
10.4.3
Physical examination
10.4.3.1
Complete physical examination 
A complete physical examination will be performed at Visit 1 (entry to study), Visit 2 (Baseline), 
Visit 8, and at ETV in case of early termination. A complete physical examination will also be 
performed at Visit 4 of the Transition Period and at the Safety Follow-Up Visit.
The complete physical examination will include cardiac and respiratory function via 
auscultation; temperature measurement, and review of all body systems.
Clinically significant physical examination findings will be reported as AEs.
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09 Feb 2017
Statistical Analysis Plan
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      SP0969
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Page 41 of 96
10.4.3.2
Brief physical examination
A brief physical examination will be performed at Visit 3 to Visit 7. A brief physical 
examination will also be performed at Visit 1 to Visit 3 of the Transition Period, and at Week 18, 
19, or 20 of the Taper Period, as appropriate.
The brief physical examination will include a review of the following body systems:

Cardiovascular

Pulmonary

Abdominal (hepato-gastrointestinal)

Dermatologic
Clinically significant physical examination findings will be reported as AEs.
10.4.4
Neurological examination
10.4.4.1
Complete neurological examination
A complete neurological examination will be performed at Visit 1 (entry to study), Visit 2 
(Baseline), Visit 8, and at ETV in case of early termination. A complete neurological 
examination will also be performed at Visit 4 of the Transition Period and at the Safety Follow-
Up Visit.
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.
Summaries of shift from Baseline to Last Visit will be provided by treatment group based on 
categories normal, abnormal, not clinically significant, and abnormal, clinically significant. A 
listing of abnormal neurological examination findings from the complete neurological 
examination will also be provided. 
Clinically significant neurological findings will be reported as AEs.
10.4.4.2
Brief neurological examination
A brief neurological examination will be performed at Visit 3 to Visit 7. A brief neurological 
examination will also be performed at Visit 1 to Visit 3 of the Transition Period, and at Week 18, 
19, or 20 of the Taper Period, as appropriate.
The brief neurological examination will include selected assessment of: general neurological 
status, reflexes, muscle strength, and coordination/cerebella function.
A listing of abnormal neurological examination findings from the brief neurological examination 
will also be provided. No summaries of the brief neurological examination findings are planned.
Clinically significant neurological findings will be reported as AEs.
10.4.5
Vagus nerve stimulation
Vagus nerve stimulation status is recorded throughout the study from Visit 1 (entry to study) to 
Visit 8, and at ETV in case of early termination, and at unscheduled visit, only for subjects with 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 42 of 96
an implanted VNS device. VNS status will also be assessed during the Transition Period, Taper 
Period, and at the Safety Follow-Up Visit only for those patients with an implanted VNS device. 
A listing of VNS status will be provided only for those subjects with an implanted VNS device. 
No summaries of VNS data are planned.
10.4.6
Tanner stage assessment
The investigator will evaluate the subject’s sexual development using the 3-item Tanner scale
(ie, for females: breasts, pubic hair, and overall stage; and for males: genitals, pubic hair, and 
overall stage). The investigator should use clinical judgment in deciding which subjects are 
selected for evaluation of Tanner stage (ie, those subjects who are pubescent at Visit 1 [entry to 
study] or who will enter puberty during the course of the study).
Tanner stage will be assessed at Visit 1 (entry to study) and at Visit 8, and at ETV in case of 
early termination.
A shift table will be produced showing the change in overall Tanner stage (1-5) from Baseline to 
Last Visit, by sex and treatment group. 
10.4.7
Achenbach Child Behavior Checklist
The Achenbach Child Behavior Checklist (CBCL) is completed at Visit 2 (Baseline), Visit 5 
(End of Titration Period), Visit 8, and at ETV in case of early termination. 
The Achenbach CBCL form is a questionnaire intended to evaluate a child’s competencies and 
behavioral/emotional problems. Depending on the subject’s age, 1 of 2 versions of the 
Achenbach CBCL is used. The CBCL/1½-5 is intended for use in children 18 months to 5 years 
and 11 months of age. For subjects ≥6 years to <17 years, the CBCL/6-18 will be used. For each 
subject, the same version (CBCL/1½-5 or CBCL/6-18) that is used at Visit 2 (Baseline) should be 
used at Visit 5, and Visit 8/ETV, and should be completed by the same parent/legal 
representative.  
The CBCL/1½-5 comprises 100 questions and the CBCL/6-18 comprises 120 questions with the 
response options of: 

0=not true (as far as known)

1=somewhat of sometimes true

2=very true or often true
The CBCL/1½-5 will be grouped according to syndrome scales in Table 10‒3 and the CBCL/6-
18 will be grouped according to empirically based syndrome scales in Table 10‒4.
Table 10‒3: CBCL/1½-5
Syndrome scale
Questions
Aggressive behavior
8, 15, 16, 18, 20, 27, 29, 35, 40, 42, 44, 53, 58, 66, 
69, 81, 85, 88, 96
Anxious/depressed
10, 33, 37, 43, 47, 68, 87, 90
Attention problems
5, 6, 56, 59, 95
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 43 of 96
Table 10‒3: CBCL/1½-5
Syndrome scale
Questions
Emotionally reactive
21, 46, 51, 79, 82, 83, 92, 97, 99
Sleep problems
22, 38, 48, 64, 74, 84, 94
Somatic complaints
1, 7, 12, 19, 24, 39, 45, 52, 78, 86, 93
Withdrawn
2, 4, 23, 62, 67, 70, 71, 98
Other problems
3, 9, 11, 13, 14, 17, 25, 26, 28, 30, 31, 32, 34, 36, 
41, 49, 50, 54, 55, 57, 60, 61, 63, 65, 72, 73, 75, 76, 
77, 80, 89, 91, 100
Table 10‒4: CBCL/6-18
Syndrome scale
Questions
Aggressive behavior
3, 16, 19, 20, 21, 22, 23, 37, 57, 68, 86, 87, 88, 89, 
94, 95, 97, 104
Anxious/depressed
14, 29, 30, 31, 32, 33, 35, 45, 50, 52, 71, 91, 112
Attention problems
1, 4, 8, 10, 13, 17, 41, 61, 78, 80
Rule-breaking behavior
2, 26, 28, 39, 43, 63, 67, 72, 73, 81, 82, 90, 96, 99, 
101, 105, 106
Social problems
11, 12, 25, 27, 34, 36, 38, 48, 62, 64, 79
Somatic complaints
47, 49, 51, 54, 56a, 56b, 56c, 56d, 56e, 56f, 56g
Thought problems
9, 18, 40, 46, 58, 59, 60, 66, 70, 76, 83, 84, 85, 92, 
100
Withdrawn/depressed
5, 42, 65, 69, 75, 102, 103, 111
Standardized T-scores are determined for each subject’s raw syndrome and overall scores based 
on the subject’s age and sex. Tables mapping each raw score to the appropriate T-score are 
provided in the CBCL Professional Manual and will be reproduced programmatically. 
Calculated T-score values and change from Baseline for each CBCL/1½-5 syndrome (aggressive 
behavior, anxious/depressed, attention problems, emotionally reactive, other problems, sleep 
problems, somatic complaints, and withdrawn) will be summarized for each visit, and Last Visit,
by treatment group.
Calculated T-score values and change from Baseline for each CBCL/6-18 syndrome (aggressive 
behavior, anxious/depressed, attention problems, rule-breaking behavior, social problems, 
somatic complaints, thought problems, and withdrawn/depressed) will be summarized for each 
visit, and Last Visit, by treatment group.
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UCB
09 Feb 2017
Statistical Analysis Plan
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      SP0969
Confidential
Page 44 of 96
10.4.8
Assessment of suicidality
Suicidality will be assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS). The 
scale will be used for Screening as well as to assess suicide 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.
For those subjects, signs and symptoms of depression will be assessed at each visit.
The C-SSRS assessment is completed throughout the study from Visit 1 (entry to study) to Visit 
8, and at ETV in case of early termination, and at unscheduled visits. The C-SSRS assessment is 
also completed during the Transition Period, Taper Period, and at the Safety Follow-Up Visit. 
Subject data listings of the data for the C-SSRS will be provided. No summaries of the C-SSRS 
data are planned.
10.4.9
BRIEF-P and BRIEF assessment
The BRIEF-P/BRIEF assessments are completed at Visit 2 (Baseline), Visit 8, and at ETV in 
case of early termination.
The BRIEF-P and BRIEF are validated tools that will be used for the evaluation of subjects ≥2 to 
<5 years of age, and ≥5 years of age, respectively. For each subject, the same version (BRIEF-P 
or BRIEF) that is used at Visit 2 (Baseline) should be used at Visit 8/ETV.  
10.4.9.1
BRIEF-P scores
The BRIEF-P form comprises 63 questions with entry options N (never: scored as 1 point), S 
(sometimes: scored as 2 points), and O (often: scored as 3 points).
The 63 items are included in the raw Global Executive Composite (GEC) score which ranges 
from 63 to 189, with higher scores reflecting poorer functioning.
The 3 subscale scores and 5 individual component scores that make up these subscale scores are 
outlined in Table 10‒5.
Table 10‒5: BRIEF-P questionnaire scoring
Scale/Index
Questions
Inhibit
3, 8, 13, 18, 23, 28, 33, 38, 43, 48, 52, 54, 56, 58, 
60, 62
Shift
5,10, 15, 20, 25, 30, 35, 40, 45, 50
Emotional Control
1, 6, 11, 16, 21, 26, 31, 36, 41, 46
Inhibitory self-control
All from {Inhibit and Emotional Control}
Flexibility
All from {Shift and Emotional Control}
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09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 45 of 96
Table 10‒5: BRIEF-P questionnaire scoring
Scale/Index
Questions
Working Memory
2, 7, 12, 17, 22, 27, 32, 37, 42, 47, 51, 53, 55, 57, 
59, 61, 63
Plan/Organize
4, 9, 14, 19, 24, 29, 34, 39, 44, 49
Emergent metacognition
All from {Working Memory and Plan/Organize}
GEC Score
1-63
GEC=Global Executive Composite
Standardized T-scores are determined from each subject’s raw GEC, inhibitory self-control, 
flexibility, emergent metacognition, and component scores based on the subject’s age and sex. 
Tables that map each raw score to the appropriate T-score are provided in the BRIEF-P 
Professional Manual and will be reproduced programmatically.
Calculated T-score values and change from Baseline for the 3 indexed scores and GEC for the 
BRIEF-P questionnaire will be summarized at Visit 8, and Last Visit, by treatment group. 
All BRIEF-P assessment data will be listed.
10.4.9.2
BRIEF scores
The BRIEF form comprises 86 questions with entry options N (never: scored as 1 point), S 
(sometimes: scored as 2 points), and O (often: scored as 3 points).
The first 72 items are included in the GEC score which ranges from 72 to 216, with higher scores 
reflecting poorer functioning.
The 2 subscale scores and 8 individual component scores that make up these subscale scores are 
outlined in Table 10‒6.
Table 10‒6: BRIEF questionnaire scoring
Scale/Index
Questions
Inhibit
38, 41, 43, 44, 49, 54, 55, 56, 59, 65
Shift
5, 6, 8, 12, 13, 23, 30, 39
Emotional Control
1, 7, 20, 25, 26, 45, 50, 62, 64, 70
Behavioral Regulation Index (BRI)
All from {Inhibit, Shift, and Emotional Control}
Initiate
3, 10, 16, 47, 48, 61, 66, 71
Working Memory
2, 9, 17, 19, 24, 27, 32, 33, 37, 57
Plan/Organize
11, 15, 18, 22, 35, 36, 40, 46, 51, 53, 58
Organization of Materials
4, 29, 67, 68, 69, 72
Monitor
14, 21, 31, 34, 42, 52, 60, 63
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09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 46 of 96
Table 10‒6: BRIEF questionnaire scoring
Scale/Index
Questions
Metacognition Index (MI)
All from {Initiate, Working Memory, 
Plan/Organize, Organization of Materials, and 
Monitor}
GEC Score
1-72
The BRI score is the total of 28 items and ranges from 28-84. The MI score is the total of 44 
items and ranges from 44 to 132.
Standardized T-scores are determined from each subject’s raw GEC, BRI, MI, and component 
scores based on the subject’s age and sex. Tables that map each raw score to the appropriate T-
score are provided in the BRIEF Professional Manual and will be reproduced programmatically.
Calculated T-score values and change from Baseline for the 2 indexed scores (BRI and MI), and 
GEC for the BRIEF questionnaire will be summarized at Visit 8, and Last Visit, by treatment 
group. 
All BRIEF assessment data will be listed.
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Statistical Analysis Plan
Lacosamide
      SP0969
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11
REFERENCES
Cardiocore. Project Charter SP847. A multicenter , open-label study to investigate the safety, 
tolerability and pharmacokinetics of lacosamide oral solution (syrup) as adjunctive therapy in 
children with partial-onset seizures. September 2nd 2011.
Friede T, Kieser M. Sample size reassessment in non-inferiority trials. Internal pilot study 
designs with ANCOVA. Methods of Information in Medicine 2011;50:237-243.
National Center for Health Statistics in collaboration with the National Center for Chronic 
Disease Prevention and Health Promotion. 2000. ttp://www.cdc.gov/growthcharts (accessed 23 
Dec 2013).
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Statistical Analysis Plan
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12
APPENDICES
12.1
Marked abnormality criteria for laboratory data
12.1.1
Marked abnormality criteria for hematology data
Table 12‒1: Hematology abnormality criteria
Parameter
Age Range
Unit 
(conventional)
Abnormality  
criteria 
(conventional 
unit)
Unit 
(standard)
Abnormality 
criteria 
(standard 
unit)
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
g/dL
≤9.5
>16.0
g/L
≤95
>160
≥17y
g/dL
≤85% of LLN
≥115% of ULN
g/L
≤85% of LLN
≥115% of ULN
WBC/ 
Leukocytes
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
109/L
<0.7
>6.9
G/L
<0.7
>6.9
≥6y
109/L
<0.6
>5.0
G/L
<0.6
>5.0
Basophils
>1m
%
≥5.0
%
≥5.0
Basophils 
Absolute
>1m
109/L
≥0.4
G/L
≥0.4
Eosinophils
>1m
%
≥10
%
≥10
Eosinophils 
Absolute
>1m
109/L
≥1.0
G/L
≥1.0
Monocytes
>1m
%
≥20.0
%
≥20.0
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 49 of 96
Table 12‒1: Hematology abnormality criteria
Parameter
Age Range
Unit 
(conventional)
Abnormality  
criteria 
(conventional 
unit)
Unit 
(standard)
Abnormality 
criteria 
(standard 
unit)
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
1012/L
<3.5
T/L
<3.5
Abbreviations: m =month, y = year. A month is defined as 30 days; a year is defined as 365.25 days.
12.1.2
Marked abnormality criteria for chemistry data
Table 12‒2: Chemistry abnormality criteria
Parameter
Age Range
Unit 
(conventional)
Abnormality  
criteria 
(conventional 
unit)
Unit 
(standard)
Abnormality 
criteria 
(standard 
unit)
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
Alkaline 
Phosphatase
<4y
U/L
≥690
U/L
≥690
4y - <10y
U/L
≥834
U/L
≥834
10y - <17y
U/L
≥1761
U/L
≥1761
≥17y
U/L
≥3.0 x ULN
U/L
≥3.0 x ULN
GGT
<6m
U/L
≥522
U/L
≥522
6m - <1y
U/L
≥279
U/L
≥279
1y - <13y
U/L
≥66
U/L
≥66
13y - <17y
U/L
≥126
U/L
≥126
≥17y
U/L
≥3.0 x ULN
U/L
≥3.0 x ULN
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 50 of 96
Table 12‒2: Chemistry abnormality criteria
Parameter
Age Range
Unit 
(conventional)
Abnormality  
criteria 
(conventional 
unit)
Unit 
(standard)
Abnormality 
criteria 
(standard 
unit)
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
g/dL
<4.3
>12.0
g/L
<43
>120
≥17y
g/dL
<4.3
>13.0
g/L
<43
>130
Albumin
<1y
g/dL
<1.6
>7.2
g/L
<16
>72
≥1y - <17y
g/dL
<2.4
>8.4
g/L
<24
>84
≥17y
g/dL
<2.6
g/L
<26
BUN
<1y
mg/dL
≥24
mmol/L
≥8.568
1y - <17y
mg/dL
≥36
mmol/L
≥12.852
≥17y
mg/dL
≥40
mmol/L
≥14.28
Urea
<1y
mg/dL
>42
mmol/L
>7.014
≥1y
mg/dL
>60
mmol/L
>10.02
Creatinine
1y - <10y
mg/dL
>1.2
umol/L
>106.8
10y - <16y
mg/dL
>1.8
umol/L
>159.12
≥16y
mg/dL
≥2.0
umol/L
≥176.8
Creatinine 
Clearancea b
All
mL/min
<50
mL/s
<0.835
Bicarbonate
>1m - <17y
mEq/L
<15
>38
mmol/L
<15
>38
≥17y
mEq/L
<18
>38
mmol/L
<18
>38
Calcium
<1y
mg/dL
<6.9
>12.2
mmol/L
<1.725
>3.05
1y - <17y
mg/dL
<7.4
>11.7
mmol/L
<1.85
>2.925
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 51 of 96
Table 12‒2: Chemistry abnormality criteria
Parameter
Age Range
Unit 
(conventional)
Abnormality  
criteria 
(conventional 
unit)
Unit 
(standard)
Abnormality 
criteria 
(standard 
unit)
≥17y
mg/dL
≤7.6
≥11.0
mmol/L
≤1.9
≥2.75
Chloride
>1m
mEq/L
≤90
≥112
mmol/L
≤90
≥112
Phosphorous
<1y
mg/dL
<1.8
>8.2
mmol/L
<0.5814
>2.6486
1y - <17y
mg/dL
<1.8
>7.4
mmol/L
<0.5814
>2.3902
≥17y
mg/dL
≤2.0
≥6.0
mmol/L
≤0.646
≥1.938
Potassium
<1y
mEq/L
≤3.0
≥6.5
mmol/L
≤3.0
≥6.5
≥1y
mEq/L
≤3.0
≥6.0
mmol/L
≤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
mg/dL
<50
≥200
mmol/L
<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
mg/dL
>200
mmol/L
>5.18
HDL
≤2y
mg/dL
<10
mmol/L
<0.259
>2y
mg/dL
<20
mmol/L
<0.518
Triglycerides
<1y
mg/dL
>750
mmol/L
>8.475
≥1y
mg/dL
>300
mmol/L
>3.39
Uric Acid
<1y
mg/dL
>7.7
umol/L
>457.996
1y - <13y
mg/dL
>6.5
umol/L
>386.62
REDACTED COPY 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 52 of 96
Table 12‒2: Chemistry abnormality criteria
Parameter
Age Range
Unit 
(conventional)
Abnormality  
criteria 
(conventional 
unit)
Unit 
(standard)
Abnormality 
criteria 
(standard 
unit)
13y - <17y
mg/dL
>8.6
umol/L
>511.528
≥17y
mg/dL
>9.5
umol/L
>565.06
Thyroxine (T4)
<1y
ug/dL
≤4.3
≥18.4
nmol/L
≤55.3453
≥236.8264
≥1y
ug/dL
≤3.8
≥13.5
nmol/L
≤48.9098
≥173.7585
Globulin
<1y
g/dL
<1.0
>4.5
g/L
<10
>45
≥1y
g/dL
<1.2
>5.3
g/L
<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)
a Schwartz equation (patients <12): Cr Cl ml/min = [Height (cm) * 0.55] / serum creatinine
b Cockroft equation (patients >12): Male: Cr Cl ml/min = [(140-age) x body weight (kg)] / (72 x serum creatinine); 
Female: Cr Cl ml/min = [(140-age) x body weight (kg)] / (72 x serum creatinine)] x 0.85
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t (kg)] / 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 53 of 96
12.2
Other significant adverse events
MedDRA Preferred Term
HEPATOTOXICITY RELATED TERMS
Hepatitis toxic
Hepatotoxicity
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
SUICIDALITY RELATED TERMS
Completed suicide
Depression suicidal
Suicidal behavior
Suicidal ideation
Suicide attempt
Intentional self-injury
Self injurious behavior
Self-injurious ideation
Intentional overdose
Multiple drug overdose intentional
Poisoning deliberate
ADDITIONAL TERMS
Loss of consciousness
Syncope
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 54 of 96
13
AMENDMENTS TO THE STATISTICAL ANALYSIS PLAN
13.1
Amendment 1
The primary purpose of this substantial amendment is for consistency with other SAPs and 
protocols in the LCM pediatric program.
Global change
The following global change was made throughout the SAP:

Last Value has been changed to Last Visit

WHO-DD has been changed to WHODD

For AEs, primary SOC is now written as MedDRA primary SOC

References to Appendix 12 (Table 12.2) have been changed to reference Appendix 12 
(section 12.2)
Specific changes
Change #1
Added ANCOVA – analysis of covariance to the list of abbreviations
Added MA – markedly abnormal to the list of abbreviations.
Change #2
The statistical analysis plan signature page has been removed and the new e-signature page has 
been included in its place.
Change #3
Section 2.2.1.3 Other efficacy variables
Other efficacy variables to be examined include:

Clinical Global Impression of Change at the end of the Maintenance Period

Caregiver’s Global Impression of Change at the end of the Maintenance Period

Quality of life assessments (PedsQL)

Health care resource use (concomitant AEDs, medical procedures, health care provider 
consultations not related to study, hospitalizations not related to study)  
Has been changed to:
Other efficacy variables to be examined include:

Clinical Global Impression of Change at the end of the Maintenance Period

Caregiver’s Global Impression of Change at the end of the Maintenance Period

Quality of life assessments (PedsQL)

Health care resource use (concomitant AEDs, medical procedures, health care provider 
consultations including hospitalizations not foreseen by the protocol)  
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
      SP0969
Confidential
Page 55 of 96
Change #4
Section 2.3 Study design and conduct
Subjects who complete the Maintenance Period and plan to participate in the open-label 
extension study (EP0034) will enter a 4-week blinded Transition Period. Subjects randomized to 
LCM will maintain their Maintenance Period dose during the Transition Period. Subjects 
randomized to placebo will transition to LCM in a double-blind fashion in accordance with the 
schedule provided in Table 3-4.
The blinded Taper Period (2 to 4 weeks, depending on dose level achieved) is for subjects who 
will not be entering the open-label extension study (EP0034) for any of the following reasons:

Subject does not complete the Titration Period, the Maintenance Period, or the Transition 
Period

Subject does not choose to enroll in the open-label extension study (EP0034) after 
completing the Maintenance Period or the Transition Period
Taper of LCM may not be required for some subjects who discontinue study medication 
prematurely, depending on the treatment option selected by the investigator in consultation with 
the subject and/or parent/legal representative.
The dosing of study medication for the Taper Period is provided in Table 3-5.
There will be a 30-day Safety Follow-Up Period for subjects not entering the open-label 
extension study (EP0034).
Unscheduled visits can be conducted at the discretion of the investigator.
Each subject’s total duration of study medication administration is up to 24 weeks. The total 
study duration can be up to 36 weeks, including the 30-day safety Follow-Up Period.
Detailed tabular schedules of study procedures are provided in Table 2-1, Table 2-2, and        
Table 2-3. 
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UCB
09 Feb 2017
Statistical Analysis Plan
                                                                                Lacosamide
SP0969
Confidential
Page 56 of 96
Table 2-1:
Schedule of study assessments (Baseline Period, Titration Period, Maintenance Period, Early 
Termination Visit, and Unscheduled Visits)
Assessments
Baseline Period 
(8 weeks)
Treatment Period (16 weeks)
Titration Period (6 weeks)
Maintenance Period (10 weeks)
Visit
V1a
T1
V2
T2
V3
T3
V4
T4
V5
V6
T5
V7
T6
V8b
ETV
Unscheduled 
Visitc
Week in study
-8
-4
0
1
2
3
4
5
6
8
10
12
14
16
Informed consent
X
Inclusion/exclusion criteria
X
X
X
Medical history
X
Seizure history
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant AEDs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
VNS assessmentd
X
X
X
X
X
X
X
X
X
X
Physical examination 
(complete)
X
X
X
X
Physical examination (brief)
X
X
X
X
X
Tanner Stagee
X
X
X
Vital signs (BP and pulse rate, 
including orthostatic 
assessments) 
X
X
X
X
X
X
X
X
X
X
Body weight
X
X
X
X
X
X
X
X
X
X
Height
X
X
X
X
Head circumference
X
X
X
Neurological examination 
(complete)
X
X
X
X
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marketing authorization application and any extensions or variations thereof. 
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UCB
09 Feb 2017
Statistical Analysis Plan
                                                                                Lacosamide
SP0969
Confidential
Page 57 of 96
Table 2-1:
Schedule of study assessments (Baseline Period, Titration Period, Maintenance Period, Early 
Termination Visit, and Unscheduled Visits)
Assessments
Baseline Period 
(8 weeks)
Treatment Period (16 weeks)
Titration Period (6 weeks)
Maintenance Period (10 weeks)
Visit
V1a
T1
V2
T2
V3
T3
V4
T4
V5
V6
T5
V7
T6
V8b
ETV
Unscheduled 
Visitc
Week in study
-8
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1
2
3
4
5
6
8
10
12
14
16
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(brief)
X
X
X
X
X
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X
X
X
X
X
X
X
X
X
Clinical chemistry/hematology
X
X
X
X
X
X
X
Endocrinology
X
X
X
Urinalysisg
X
X
X
X
X
X
X
Serum pregnancy testh
X
X
X
X
X
X
Urine pregnancy testh
X
X
X
Concomitant AED plasma 
concentrationsi
X
X
X
X
LCM plasma concentrationi
X
X
X
X
C-SSRSj
X
X
X
X
X
X
X
X
X
X
Clinical Global Impression of 
Change
X
X
Caregiver’s Global Impression 
of Change
X
X
Achenbach CBCLk
X
X
X
X
BRIEF-P/BRIEFl
X
X
X
PedsQLm
X
X
X
Contact IXRS
X
X
X
X
X
X
X
X
X
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UCB
09 Feb 2017
Statistical Analysis Plan
                                                                                Lacosamide
SP0969
Confidential
Page 58 of 96
Table 2-1:
Schedule of study assessments (Baseline Period, Titration Period, Maintenance Period, Early 
Termination Visit, and Unscheduled Visits)
Assessments
Baseline Period 
(8 weeks)
Treatment Period (16 weeks)
Titration Period (6 weeks)
Maintenance Period (10 weeks)
Visit
V1a
T1
V2
T2
V3
T3
V4
T4
V5
V6
T5
V7
T6
V8b
ETV
Unscheduled 
Visitc
Week in study
-8
-4
0
1
2
3
4
5
6
8
10
12
14
16
Randomizationn
X
Dispense study medication
Xl
X
X
X
X
X
X
X
Study medication return
X
X
X
X
X
X
X
Subject diaryo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Withdrawal criteria
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE reporting
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Assessments of epilepsy 
surgery/VNS
X
Health care resource use
X
X
X
X
X
X
X
X
X
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; BRIEF=Behavior Rating Inventory of Executive Function; BRIEF-P=Behavior Rating 
Inventory of Executive Function-Preschool Version; CBCL=Child Behavior Checklist; C-SSRS=Columbia-Suicide Severity Rating Scale; 
ECG=electrocardiogram; ETV=Early Termination Visit; IXRS=interactive voice/web response system; LCM=lacosamide; PedsQL=Pediatric Quality of Life 
Inventory; T=Telephone Contact; V=Visit; VNS=vagus nerve stimulation
Note: For all visits shown in Table 2-1a time window of ±2 days relative to Visit 2 (Baseline Period) is applicable. During the Treatment Period, each visit 
should occur at the end of the week indicated in accordance with this time window.
aVisit 1 (V1) may occur over more than 1 day; however, all results of Visit 1 assessments should be available before T1.
bAt the end of Visit 8, subjects who complete the Maintenance Period may be eligible to participate in an open-label extension study (EP0034). Subjects who 
plan to enroll in the open-label extension study will proceed to a 4-week blinded Transition Period. Subjects who choose not to enter the open-label extension 
study or who do not complete the Maintenance Period will proceed to a blinded Taper Period (2 to 4 weeks, depending on dose level achieved). Taper of LCM 
may not be required for some subjects who discontinue study medication prematurely, depending on the treatment option selected by the investigator in 
consultation with the subject and/or parent/legal representative.
cIf an Unscheduled Visit is needed (eg, due to AE), then the assessments noted will be performed. Additional assessments may be performed at the investigator’s 
discretion. The C-SSRS will be completed at an Unscheduled Visit only if the visit is related to an AE.
dOnly applicable for subjects with an implanted VNS device.
eThe Tanner Stage will be performed only for subjects who are pubescent at Visit 1 or who enter puberty during the course of the study.
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UCB
09 Feb 2017
Statistical Analysis Plan
                                                                                Lacosamide
SP0969
Confidential
Page 59 of 96
fA 12-lead ECG (2 interpretable recordings) will be performed prior to any blood draws and vital signs assessment. The subject should rest in the supine position 
for approximately 5 minutes before the recordings and during the recordings, if possible. The recordings should be made 20 to 30 minutes apart.
gUrinalysis will be performed for subjects ≥5 years of age only.
hPregnancy tests will be performed for female subjects of childbearing potential only.
iBlood samples for analysis of concomitant AED plasma concentrations and/or LCM will be drawn along with clinical chemistry, hematology, and endocrinology 
samples, as applicable.
jThe C-SSRS will be completed for all subjects ≥6 years of age. The C-SSRS will be completed at an Unscheduled Visit only if the visit related to an AE.
kThe Achenbach CBCL: CBCL/1½ -5 for children 18 months to 5 years and 11 months of age, and CBCL/6-18 for children ≥6 years to <17 years of age; to be 
completed by the parent(s)/legal representative(s) (estimated completion time 45 minutes). For each subject, the same version of the scale that was completed at 
Visit 2 (CBCL/1½ -5 or CBCL/6-18) should be maintained for the duration of the study and should be completed by the same parent/legal representative. The 
Achenbach CBCL will be used only in countries where a translated version is available.
lThe BRIEF-P should be used for subjects who are ≥2 years to <5 years of age at Visit 2, and the BRIEF should be used for subjects who are ≥5 years of age at 
Visit 2. The same version of the scale that was completed at Visit 2 (BRIEF-P or BRIEF) should be maintained for each subject for the duration of the study. 
The BRIEF-P and BRIEF will be used only in countries where a translated version is available.
mThe version of the PedsQL used at Visit 2 should be consistent with the subject’s age at Visit 2 and should be maintained for each subject for the duration of the 
study. The PedsQL will be used only in countries where a translated version is available.
nAt the end of Visit 2, subjects should take the first dose of study medication in the clinic.
oThe subject diary will be dispensed at Visit 1. At all subsequent visits, the subject and/or legal representative(s) will be reminded to complete the diary on a 
daily basis.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 60 of 96
Table 2-2:
Schedule of study assessments (Transition Period)
Assessment
Transition Period (4 weeks)a
Visit
TV1
TV2
TV3
TV4
Week in study
17a
18
19
20
Concomitant medications
X
X
X
X
Concomitant AEDs
X
X
X
X
VNS assessmentsb
X
X
X
X
Physical examination (complete)
X
Physical examination (brief)
X
X
X
Vital signs (BP and pulse rate, including 
orthostatic assessment)
X
X
X
X
Body weight
X
X
X
X
Neurological examination (complete)
X
Neurological examination (brief)
X
X
X
12-lead ECGc
X
Clinical chemistry/hematology
X
Urinalysisd
X
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X
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concentrations
X
LCM plasma concentrationf
X
C-SSRSg
X
X
X
X
Contact IXRS
X
X
X
X
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X
X
X
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X
X
X
X
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X
X
X
X
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X
X
X
X
AE reporting
X
X
X
X
Health care resource use
X
X
X
X
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; C-SSRS=Columbia-Suicide Severity Rating Scale; 
ECG=electrocardiogram; IXRS=interactive voice/web response system; LCM=lacosamide; TV=Transition Visit; 
VNS=vagus nerve stimulation
Note: For all visits shown in , a window of ±2 days relative to Visit 2 (Baseline Period) is applicable. Each visit 
should occur at the end of the week indicated in accordance with this time window.
aAt the end of Visit 8, (Maintenance Period), subjects may be eligible to participate in an open-label extension study 
(EP0034). Subjects who plan to enroll in the open-label extension study will enter a 4-week blinded Transition 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 61 of 96
Period.
bOnly applicable for subjects with an implanted VNS device.
cA 12-lead ECG (2 interpretable recordings) will be performed prior to any blood draws and vital signs assessment. 
The subject should rest in the supine position for approximately 5 minutes before the ECG recording and during 
the recordings if possible. The recordings should be made 20 to 30 minutes apart.
dUrinalysis will be performed for subjects ≥5 years of age only.
ePregnancy tests will be performed for female subjects of childbearing potential only.
fBlood samples for analysis of concomitant AED plasma concentrations and/or LCM will be drawn along with 
clinical chemistry, hematology, and endocrinology samples, as applicable.
gThe C-SSRS will be completed for all subjects ≥6 years of age.
hThe subject diary will be returned at TV4. At all other visits, the subject and/or legal representative(s) will be 
reminded to complete the diary on a daily basis.
Table 2-3:
Schedule of study assessments (Taper Period and Safety Follow-Up 
Period)
Assessment
Taper Perioda
(2 to 4 weeks)
Safety Follow-Up Periodb
(30 days)
Visit
T7c
Taper Visitd
Safety 
Follow-Up
Visit
Safety 
Follow-Up
Telephone 
Contact
Week in study
17
18, 19, or 20
20, 21, or 22
22, 23, or 24
Concomitant medications
X
X
X
X
Concomitant AEDs
X
X
X
X
VNS assessmente
X
X
Physical examination (brief)
X
Physical examination (complete)
X
Vital signs (BP and pulse rate, 
including orthostatic assessment)
X
X
Body weight
X
X
Neurological examination (brief)
X
Neurological examination (complete)
X
ECG (12-lead)f
X
Xg
Clinical chemistry/hematology
X
Xg
Endocrinology
X
Xg
Urinalysish
X
X
Serum pregnancy test
X
Xi
Urine pregnancy test
Xi
C-SSRSj
X
X
Contact IXRS
X
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 62 of 96
Study medication return
X
Subject diaryk
X
X
Withdrawal criteria
X
X
AE reporting
X
X
X
X
Health care resource use
X
X
AE=adverse event; AED=antiepileptic drug; BP=blood pressure; C-SSRS=Columbia-Suicide Severity Rating Scale; 
ECG=electrocardiogram; IXRS=interactive voice/web response system; LCM=lacosamide; T=Telephone Contact; 
VNS=vagus nerve stimulation
Note: The study week numbers provided are for subjects who complete the Maintenance Period and enter the Taper 
Period. The study week numbers provided do not apply to subjects who enter the Taper Period at other times.
aA blinded Taper Period (2 to 4 weeks, depending on dose achieved) will be required for subjects who discontinue 
study medication prematurely and for subjects who complete the Maintenance Period but choose not to enter the 
open-label extension study (EP0034). Taper of LCM may not be required for some subjects who discontinue study 
medication prematurely, depending on the treatment option selected by the investigator in consultation with the 
subject and or parent/legal representative.
bThe Safety Follow-Up Visit will occur 2 weeks (±2 days) after the final dose of study medication. The Safety 
Follow-Up Telephone Contact will occur 30 days (-1/+3 days) after the final dose of study medication.
cA telephone contact (T7) will be conducted at the end of the first week of the Taper Period. 
dEach subject will have only 1 Taper Visit. The Taper Visit will be scheduled at the end of the Taper Period 
(Week 18, Week 19, or Week 20, depending on dose level achieved; see of the Protocol). A time window of 
±2 days relative to Visit 2 (Baseline Period) is applicable.
eOnly applicable for subjects with an implanted VNS device. 
fA 12-lead ECG (2 interpretable recordings) will be performed prior to any blood draws and vital signs assessment. 
The subject should rest in the supine position for approximately 5 minutes before the recording and during the 
recordings, if possible. The recordings should be made 20 to 30 minutes apart.
gThe assessment will only be required for subjects with an abnormal value (clinical chemistry, hematology, or 
endocrinology) or reading (ECG) at the previous clinic visit.
hUrinalysis will be performed for subjects ≥5 years of age only.
iPregnancy tests will be performed for female subjects of childbearing potential only. A serum pregnancy test will be 
performed at the Safety Follow-Up Visit only if blood is collected for other laboratory tests. If no blood is 
collected for other assessments, then a urine pregnancy test will be performed.
jThe C-SSRS will be completed for all subjects ≥6 years of age.
kAt T7, the subject and/or legal representative(s) will be reminded to complete the diary on a daily basis. The subject 
diary will be returned at the Taper Visit.
Has been changed to:
Subjects who complete the Maintenance Period and plan to participate in the open-label 
extension study (EP0034) will enter a 4-week blinded Transition Period. Subjects randomized to 
LCM will maintain their Maintenance Period dose during the Transition Period. Subjects 
randomized to placebo will transition to LCM in a double-blind fashion in accordance with the 
schedule provided in Table 7-4 of the protocol. 
The blinded Taper Period (2 to 4 weeks, depending on dose level achieved) is for subjects who 
will not be entering the open-label extension study (EP0034) for any of the following reasons:

Subject does not complete the Titration Period, the Maintenance Period, or the Transition 
Period

Subject does not choose to enroll in the open-label extension study (EP0034) after 
completing the Maintenance Period or the Transition Period
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 63 of 96
Taper of LCM may not be required for some subjects who discontinue study medication 
prematurely, depending on the treatment option selected by the investigator in consultation with 
the subject and/or parent/legal representative.
The dosing of study medication for the Taper Period is provided in Table 7-5 of the protocol .
There will be a 30-day Safety Follow-Up Period for subjects not entering the open-label 
extension study (EP0034).
Unscheduled visits can be conducted at the discretion of the investigator.
Each subject’s total duration of study medication administration is up to 24 weeks. The total 
study duration can be up to 36 weeks, including the 30-day safety Follow-Up Period.
Detailed tabular schedules of study procedures and a study schematic diagram are included in 
Sections 5.2 and 5.3 of the protocol, respectively.
Change #5
Section 3.1 General presentation of summaries and analyses
Statistical analysis and generation of tables, figures, subject data listings, and statistical output 
will be performed using SAS Version 9.1.3. All tables and listings will use Courier New font 
size 9.
Has been changed to:
Statistical analysis and generation of tables, figures, subject data listings, and statistical output 
will be performed using SAS Version 9.3. All tables and listings will use Courier New font size 
9.
Change #6
Section 3.2.2 Study periods
Maintenance Period
On or after the start of the Maintenance Period (Visit 6) and prior to or on the end date of the 
Maintenance Period (Visit 8) for subjects who complete the Maintenance Period, or on or after 
the date of first dose of study medication and prior to or on the date of the ETV for subjects who 
discontinue during the Maintenance Period. If a subject does not have a Visit 8/ETV, then either 
the date of the last scheduled or unscheduled visit during the Maintenance Period or the date of 
last known dose of study medication during the Maintenance Period, whichever is later, will 
define the end date of the Maintenance Period.
Has been changed to:
Maintenance Period
The day after the end of the Titration Period (Visit 5) and prior to or on the end date of the 
Maintenance Period (Visit 8) for subjects who complete the Maintenance Period, or on or after 
the date of first dose of study medication and prior to or on the date of the ETV for subjects who 
discontinue during the Maintenance Period. If a subject does not have a Visit 8/ETV, then either 
the date of the last scheduled or unscheduled visit during the Maintenance Period or the date of 
last known dose of study medication during the Maintenance Period, whichever is later, will 
define the end date of the Maintenance Period.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 64 of 96
Change #7
Section 3.2.4 Last Value on study medication
The Last Value on study medication for all assessments is the last available result obtained after 
first dose of study medication and prior to or on the last dose of study medication. All scheduled
and unscheduled assessments within this time period will be considered. Last Value will be 
determined separately for each vital sign, ECG, and laboratory parameter.
Has been changed to:
Section 3.2.4 Last Visit 
The Last Visit for all assessments is the last non-missing assessment during the Treatment 
Period. All scheduled and unscheduled assessments within this time period will be considered. 
Last Visit will be determined separately for each study procedure where Last Visit is mentioned 
within this document.
Change #8
Section 3.4 Protocol deviations
Important protocol deviations are deviations from the protocol which could potentially have a 
meaningful impact on either the primary efficacy outcome or key safety outcomes for an 
individual subject. The criteria for identifying important protocol deviations and the 
classification of important protocol deviations will be defined separately in the Specification of 
Protocol Deviations (SPD) document. To the extent feasible, rules for identifying protocol 
deviations will be defined without review of the data and without consideration of the frequency 
of occurrence of such deviations. Whenever possible, criteria for identifying important protocol 
deviations will be implemented algorithmically to ensure consistency in the classification of 
important protocol deviations across all subjects.
Important protocol deviations will be reviewed as part of the blinded Data Evaluation Meeting 
(DEM) prior to unblinding of the database. 
Has been changed to:
Important protocol deviations are deviations from the protocol which could potentially have a 
meaningful impact on either the primary efficacy outcome or key safety outcomes for an 
individual subject. The criteria for identifying important protocol deviations and the 
classification of important protocol deviations will be defined separately in an important protocol 
deviations document. To the extent feasible, rules for identifying protocol deviations will be 
defined without review of the data and without consideration of the frequency of occurrence of 
such deviations. Whenever possible, criteria for identifying important protocol deviations will be 
implemented algorithmically to ensure consistency in the classification of important protocol 
deviations across all subjects.
In general, protocol deviations will be considered according to the following general categories:

Inclusion criteria

Exclusion criteria

Withdrawal criteria
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 65 of 96

Prohibited concomitant medications

LCM dosing regimen

Procedural non-compliance
Important protocol deviations will be reviewed as part of the blinded Data Evaluation Meetings
(DEMs) prior to unblinding of the database. A list of subjects with important protocol deviations 
will be agreed upon during the DEMs and will be documented in the DEM minutes.
Change #9
Section 3.5 Analysis sets
The analysis sets defined for this study are the Safety Set (SS), Full Analysis Set (FAS), Per 
Protocol Set (PPS), and PK Set (PK-PPS).
Has been changed to:
The analysis sets defined for this study are the Safety Set (SS), Full Analysis Set (FAS), Per 
Protocol Set (PPS), and Pharmacokinetic Per Protocol Set (PK-PPS).
Change #10
Section 3.5.4 Pharmacokinetic Set
All subjects from the SS with valid LCM plasma concentration data will be included in the PK-
PPS. 
Has been changed to:
Section 3.5.4 Pharmacokinetic Per Protocol Set
The PK-PPS will consist of all subjects having provided at least 1 measurable post-dose plasma 
sample (with recorded sampling time) on at least 1 visit with documented study medication
intake times. 
Change #11
Section 3.6 Treatment assignment and treatment groups
It is expected that subjects will receive treatment as randomized. Thus, treatment assignment for 
the FAS and the SS will be according to randomization. However, if after unblinding it is 
determined that the subjects received treatment other than what they were randomized to receive, 
the safety analyses will be conducted using treatment assignments according to the actual 
treatment received (SS-as treated).
The recommended dosing schedule for LCM or matching placebo during the Titration Period is 
detailed in Table 3-1. The dosing of LCM or matching placebo with flexibility based on 
tolerability during the Titration Period is detailed in Table 3-2. The required LCM or matching 
placebo dose for at least the final 3 days of Week 6 is detailed in Table 3-3. Similarly, Transition 
Period LCM dosing schedule for subjects randomized to placebo, and Taper Period dosing of 
LCM or matching placebo, are detailed in Table 3-4 and Table 3-5, respectively.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 66 of 96
Table 3-1:
Recommended dosing schedule for LCM (or matching placebo) 
during the Titration Period
Body weight 
category 
(formulation)
Target LCM (or matching placebo) doses for the Titration Period
Week 1a
Week 2
Week 3
Week 4
Week 5
Week 6
<30kg (oral 
solution)
2mg/kg/day
4mg/kg/day
6mg/kg/day
8mg/kg/day
10mg/kg/day
12mg/kg/day
≥30kg to <50kg 
(oral solution)
2mg/kg/day
4mg/kg/day
6mg/kg/day
8mg/kg/day
8mg/kg/day
8mg/kg/day
≥50kg (tablets)
100mg/day
200mg/day
300mg/day
400mg/day
400mg/day
400mg/day
LCM=lacosamide
Note: Subjects may not receive doses higher than LCM 12mg/kg/day (body weight <30kg), LCM 8mg/kg/day (body 
weight ≥30kg to <50kg), or LCM 400mg/day (body weight ≥50kg), or matching placebo. 
aAll subjects are required to complete Week 1 study medication dosing before dosing flexibility is allowed based on 
tolerability. Subjects who are unable to complete the Titration Period or subjects who will not be able to attain at 
least the minimum Maintenance Period target dose, should be withdrawn and enter the Taper Period.
Table 3-2:
Dosing of LCM (or matching placebo) with flexibility based on 
tolerability during the Titration Period
Body weight category
(formulation)
Target LCM (or 
matching 
placebo) dose 
increase/weeka
(titration)
LCM (or matching placebo) 
dose decrease per
back titration step
Subsequent LCM (or 
matching placebo) dose 
increaseb
(dose increase after back 
titration step)
Min
Max
Min
Max
<30kg (oral solution)
2mg/kg/day
1mg/kg/day
2mg/kg/day
1mg/kg/day
2mg/kg/day
≥30kg to <50kg (oral 
solution)
≥50kg (tablets)
100mg/day
50mg/day
100mg/day
50mg/day
100mg/day
LCM=lacosamide; Max=maximum; Min=minimum
Note: Asymmetrical dosing with no more than 50mg difference between morning and evening doses will be allowed 
for subjects taking tablets who require back titration in a 50mg increment (ie, only 50mg and 100mg tablets are 
available)
a Titration step to achieve a dose not previously administered
b Titration step subsequent to a back titration
Table 3-3:
Required LCM (or matching placebo) dose for at least the final 3 days 
of Week 6
Body weight category
(formulation)
LCM (or matching placebo) dose for at least the final 3 days of Week 6
Min
Max
<30kg (oral solution)
8mg/kg/day
12mg/kg/day
≥30kg to <50kg (oral solution)
6mg/kg/day
8mg/kg/day
≥50kg (tablets)
300mg/day
400mg/day
LCM=lacosamide; Max=maximum; Min=minimum
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 67 of 96
Table 3-4:
Transition Period LCM dosing schedule for subjects randomized to 
placebo
Body weight category 
(formulation)
LCM doses for the Transition Period 
Week 17
Week 18
Week 19
Week 20
<30kg (oral solution)
2mg/kg/day
4mg/kg/day
6mg/kg/day
8mg/kg/day
≥30kg to <50kg (oral solution) 
2mg/kg/day
4mg/kg/day
6mg/kg/day
6mg/kg/day
≥50kg (tablets)
100mg/day
200mg/day
300mg/day
300mg/day
LCM=lacosamide
Table 3-5:
Taper Period dosing of LCM (or matching placebo) 
LCM (or matching 
placebo) dose 
achieved
LCM (or matching placebo) doses for the Taper Period 
Week 17
Week 18
Week 19
Week 20
11 or 12mg/kg/day
9mg/kg/day
6mg/kg/day
4mg/kg/day
2mg/kg/day
9 or 10mg/kg/day
8mg/kg/day
6mg/kg/day
4mg/kg/day
2mg/kg/day
7 or 8mg/kg/day
6mg/kg/day
4mg/kg/day
2mg/kg/day
2mg/kg/day
5 or 6mg/kg/day
4mg/kg/day
2mg/kg/day
2mg/kg/day
NA
3 or 4mg/kg/day
2mg/kg/day
2mg/kg/day
NA
NA
2mg/kg/day
NA
NA
NA
NA
350 or 400mg/day
300mg/day
200mg/day
100mg/day
100mg/day
250 or 300 mg/day
200mg/day
100mg/day
100mg/day
NA
150 or 200mg/day
100mg/day
100mg/day
NA
NA
100mg/day
NA
NA
NA
NA
LCM=lacosamide; NA=not applicable (taper not required)
Note: The oral solution is dosed as mg/kg/day and tablets are dosed as mg/day.
Note: Subjects not requiring taper will enter directly into the Safety Follow-Up Period and not attend any Taper 
Period visits.
Note: The study week numbers provided are for subjects who complete the Maintenance Period and enter the Taper 
Period. The study week numbers provided do not apply to subjects who enter the Taper Period at other times.
Has been changed to:
It is expected that subjects will receive treatment as randomized. Thus, treatment assignment for 
the FAS and the SS will be according to randomization. However, if after unblinding it is 
determined that the subjects received treatment other than what they were randomized to receive, 
the safety analyses will be conducted using treatment assignments according to the actual 
treatment received (SS-as treated).
All subjects treated in this study receive LCM at doses ranging from 8mg/kg/day to 12mg/kg/day 
(oral solution) for subjects weighing <30kg, 6mg/kg/day to 8mg/kg/day (oral solution) for 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 68 of 96
subjects weighing ≥30kg to <50kg, 300mg/day to 400mg/day (tablets) for subjects weighing  
≥50kg, or matching placebo. The subject’s body weight at Baseline (Visit 2) will be used to 
determine dose throughout the study. Summaries will be presented based on treatment group; 
Placebo and LCM, and will generally not be differentiated by LCM dose. Where appropriate, 
LCM dose will be presented in subject data listings.
Change #12
Section 4.2 Handling of dropouts or missing data
For subjects who discontinue prior to the Maintenance Period, all available seizure frequency 
data will be carried forward from the Titration Period for the Maintenance Period analysis. For 
subjects who prematurely discontinue during the Maintenance Period, all available seizure 
frequency data in the Maintenance Period will be carried forward for the entire Maintenance 
Period. 
Subjects who discontinue prior to any efficacy data collection will not be included in the analysis 
(ie, data will not be carried forward from Baseline). The imputation for the seizure frequency
data will not carry forward into the Transition and Taper Periods.
No imputation of missing values associated with an individual date or visit is planned for the 
primary safety analysis, with the exception of partial date information for AEs and concomitant 
medications in order to determine whether they are treatment-emergent.   
Adverse events with an incomplete onset date will be classified as a treatment-emergent adverse 
event (TEAE) if the month and year of onset (when only the month and year are specified) is the 
same as the month and years of the first dose of study medication, or the year of onset (when 
only year is specified) is the same as the year of first dose of study medication.
Has been changed to:
Section 4.2 Handling of dropouts or missing data
Section 4.2.1 Missing data
For subjects who discontinue prior to the Maintenance Period, all available seizure frequency 
data will be carried forward from the Titration Period for the Maintenance Period analysis. For 
subjects who prematurely discontinue during the Maintenance Period, all available seizure 
frequency data in the Maintenance Period will be carried forward for the entire Maintenance 
Period. 
Subjects who discontinue prior to any efficacy data collection will not be included in the analysis 
(ie, data will not be carried forward from Baseline). The imputation for the seizure frequency 
data will not carry forward into the Transition and Taper Periods.
No imputation of missing values associated with an individual date or visit is planned for the 
primary safety analysis, with the exception of partial date information for AEs and concomitant 
medications in order to determine whether the AEs are treatment-emergent or the medications 
are concomitant.   
With respect to AEs, events with missing intensity will be assumed to be severe. Events with 
missing relationship to study medication per the investigator will be assumed to be related. 
Incomplete or missing dates for events will be handled as described in section 3.2.2.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 69 of 96
Section 4.2.2 Incomplete dates for adverse events and concomitant medications
For analyses of AEs and concomitant medication usage, a complete date must be established in 
order to correctly identify the AE or medication as occurring during treatment or not. For 
purposes of imputing missing components of partially-reported start and stop dates for AEs and 
for medication use, the algorithms listed below will be followed. Start and stop dates of AEs or 
concomitant medication will be displayed as reported in the subject data listings (ie, no imputed 
values will be displayed in data listings).

Missing start day, but month and year present:
If the start of study medication occurred in the same month and year as the occurrence of 
the AE/concomitant medication, the start day of the event/concomitant medication will be 
assigned to the day of first intake of study medication. Otherwise the start day will be set 
to the 1st day of the month.

Missing start day and month, but year present:
If the start of study medication occurred in the same year as the occurrence of the 
AE/concomitant medication, the start day and month will be assigned to the date of first 
intake of study medication. Otherwise the start day and month will be set to January 1st.

Missing end day, but month and year present:
The end day will be set to the last day of the month.

Missing end day and month, but year present:
The end day and month will be set to the maximum of the date of study termination or the 
date equivalent to 28 days after last intake of study medication. 
However, if the study termination year and year for the date which is 28 days after last intake of 
study medication are greater than the event/concomitant medication year, the day and month are 
to be set to December 31st.
Section 4.2.3 Definition of concomitant medication in case of missing dates
With respect to definition of medication as concomitant, the following rule will be applied in 
case of completely missing stop and/or start date information: 
Medications with a missing start date whose stop date is either unknown or after the date of the 
first dose of study medication will be considered as concomitant medication. Medications with 
missing start date whose stop date is prior to first intake of study medication will not be 
considered concomitant.
In subject data listings, dates will be displayed as reported.
Section 4.2.4 Incomplete dates for the last administration of study medication
For purposes of imputing missing components of partially reported dates for the last 
administration of study medication, the algorithms listed below will be followed. Stop dates of 
study medication will be displayed as reported in the subject data listings (ie, no imputed values 
will be displayed in data listing).
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 70 of 96

Missing last administration day, but month and year present:
The last administration day will be set to the last day of the month or the date of the final 
contact, whichever is earlier in the month.

Missing last administration day and month, but year present:
The last administration day will be set to the last day of the year or the date of the final 
contact, whichever is earlier in the year.

Completely missing date of last administration:
For calculating the duration of exposure, if the date of last administration is completely 
missing and no information could be obtained from data cleaning exercises, the date of 
last administration should be imputed as the date of last contact according to the Study 
Termination eCRF module. For all other purposes, no imputation will be done if the date 
of last administration is completely missing.
If a subject died during the study, and the imputed last administration date according to the rules 
above is after the date of death, the last administration date will be assigned to the date of death.
Section 4.2.5 Incomplete dates for seizure diary data
Seizure frequency and seizure-free days will be calculated over non-missing diary days during 
each time interval; days for which seizure diary data were not obtained will not be considered in 
the calculation of seizure frequency or seizure-free days. If more than 10% of the diary entries 
are missing for a specific subject and time interval, then that subject will not be considered for 
the calculation of seizure frequency or seizure-free days during the time interval.
Section 4.2.6 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:

Start and stop dates of AEs

Start and stop dates of concomitant medication

Start and stop dates of study medication

Start and stop dates of seizure diary data
Completely missing dates will not be replaced and the corresponding derived variables will be 
set to missing.
Change #13
Section 4.3 Interim analyses and data monitoring
To ensure subject safety, interim reviews of the safety data will be performed using an 
Independent Data monitoring Committee (IDMC). Serious adverse events and other significant 
events (detailed in Appendix 12 (Table 12.2) are monitored and will be triaged by the medical 
monitor and UCB Drug Safety in real time.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 71 of 96
Has been changed to:
No informal interim analysis for determination of efficacy is planned for this study. To ensure 
subject safety, interim reviews of the safety data will be performed using an Independent Data 
monitoring Committee (IDMC). Serious adverse events and other significant events (detailed in 
Appendix 12 (Table 12.2) are monitored and will be triaged by the medical monitor and UCB 
Drug Safety in real time.
Change #14
Section 4.6 Use of an efficacy subset of subjects
The PPS will be used to evaluate subjects who have efficacy data during the entire treatment 
period and have no important protocol deviations related to efficacy. This analysis set will 
provide additional information on the analysis of the primary efficacy variable and will describe 
findings in a subset of subjects who more closely followed the intentions of the study protocol.
Has been changed to:
The primary efficacy variable will also be analyzed for the PPS. This analysis set will provide 
additional information on the analysis of the primary efficacy variable and the impact of the 
important protocol deviations on efficacy.
Change #15
Section 5.1 Subject disposition
The date of first subject in, date of last subject out, number of enrolled subjects, and the number 
of subjects randomized, number of subjects in each treatment group, and overall, and the number 
of subjects in each analysis set (SS, FAS, PPS and PK-PPS), will be summarized overall and by 
investigator site. Subjects who transferred sites will be summarized according to their original 
site. 
Has been changed to:
The date of first subject in, date of last subject out, number of enrolled subjects, and the number 
of subjects randomized, number of subjects in each treatment group, and overall, and the number 
of subjects in each analysis set (SS, FAS, PPS and PK-PPS), will be summarized overall and by 
investigator site. Subjects who transferred sites will be summarized according to their original 
site. 
A summary of discontinuations due to AEs for all screened subjects will present the number and 
percentage of subjects who discontinued this study due to AEs broken down by type of AE.
The number and percentage of subjects enrolled under each protocol amendment (estimated by 
date of informed consent) will be presented. This will also be presented in the subjects data 
listings.
Change #16
Section 5.2 Protocol deviations
Important protocol deviations defined in the SPD, and additionally identified at the DEM before 
unblinding of the database will be listed including their associated categories (safety, efficacy or 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 72 of 96
study conduct).  In addition, the number and percentage of subjects with at least 1 important 
protocol deviation will be summarized overall and by category of important protocol deviation 
for the SS. The number and percentage of subjects with no important protocol deviations will 
also be summarized for the SS.
Has been changed to:
Important protocol deviations defined in the important protocol deviation document, and 
additionally identified at the DEMs before unblinding of the database will be listed.  In addition, 
the number and percentage of subjects with at least 1 important protocol deviation will be 
summarized overall and by category of important protocol deviation for the SS. The number and 
percentage of subjects with no important protocol deviations will also be summarized for the SS.
Change #17
Section 6.1 Demographic and baseline characteristics
Age, age category (≥4 to <12, and ≥12 to <17 years of age), gender, race (American 
Indian/Alaskan Native, Asian, Black, Native Hawaiian or Other Pacific Islander, White, and 
Other/Mixed), ethnicity (Hispanic or Latino, and not Hispanic or Latino), weight (kg), height 
(cm), BMI (kg/m2), BMI category (<18.5, 18.5 to <25, 25 to <30, ≥30 kg/m2), and head 
circumference will be summarized by treatment group and overall for the SS, and repeated by 
treatment group and age group, using the levels defined in section 4.8.
Has been changed to:
Age, age category (≥4 to <12, and ≥12 to <17 years of age), EudraCT age category (≥24 months 
to <12 years, and ≥12 to <18 years), gender, weight (kg), weight band (<30,  ≥30 to <50,  ≥50 
kg), height (cm), BMI (kg/m2),  racial group (American Indian/Alaskan Native, Asian, Black, 
Native Hawaiian or Other Pacific Islander, White, and Other/Mixed), ethnicity (Hispanic or 
Latino, and not Hispanic or Latino), and vagus nerve stimulation (VNS) use (Active VNS, No 
VNS, and VNS not active) will be summarized by treatment group and overall for the SS, and 
repeated by treatment group and age group, using the levels defined in section 4.8.
Change #18
Section 6.4 Prior and concomitant medications
A listing of all medications taken during the study will be presented.
Medications will be attributed to the study periods as defined in section 3.2.2 based on the start 
date of the medication.
Section 6.4.1 Number of Lifetime AEDs
The number of lifetime AEDs defined as AEDs taken and stopped >28 days prior to Visit 1 (ie, 
prior to entry into the Baseline Period), will be summarized by treatment group and overall for 
the SS based on the following categorization: 1 to 3 AEDs, 4-6 AEDs, and ≥7 AEDs.
Section 6.4.2 Number of AEDs taken at study entry
The number of AEDs taken at study entry will be summarized by treatment group and overall for 
the SS based on the following categorization: 1 AEDs, 2 AEDs, and 3 AEDs. 
Section 6.4.3 AEDs taken at study entry
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 73 of 96
The number and percentage of subjects taking AEDs at the time of study entry will be 
summarized by WHO-DD chemical subgroup (Level 4) and preferred drug name, and by 
treatment group and overall for the SS. 
Section 6.4.4 Concomitant AEDs
The number and percentage of subjects taking concomitant AEDs during the Baseline Period and 
during the entire Treatment Period will be summarized, separately, by WHO-DD chemical 
subgroup (Level 4) and preferred drug name, and by treatment group and overall for the SS. 
Vagus nerve stimulation (VNS) is allowed and will not be counted as a concomitant AED.
Section 6.4.5 Prior medications (excluding AEDs)
The number and percentage of subjects taking non-AEDs at the time of study entry will be 
summarized by WHO-DD anatomical main group (Level 1) and therapeutic subgroup (Level 2), 
and by treatment group and overall for the SS. 
Section 6.4.6 Concomitant medications (excluding AEDs)
The number and percentage of subjects taking concomitant non-AEDs during the study will be 
summarized by WHODD anatomical main group (Level 1) and therapeutic subgroup (Level 2), 
and by treatment group and overall for the SS.
Has been changed to:
Section 6.4 Prior and concomitant medications
A listing of all medications taken during the study will be presented.
Medications will be attributed to the study periods as defined in section 3.2.2 based on the start 
date of the medication.
Section 6.4.1 Number of Lifetime AEDs 
The number of lifetime AEDs defined as AEDs taken and stopped >28 days prior to Visit 1 (ie, 
prior to entry into the Baseline Period), will be summarized by treatment group and overall for 
the SS based on the following categorization: 1 to 3 AEDs, 4-6 AEDs, and ≥7 AEDs.
Section 6.4.2 Number of AEDs taken prior to the Baseline Period
The number of AEDs taken prior to the Baseline Period defined as AEDs with a start date prior 
to the date of informed consent, ie, prior to entry into the Baseline Period, excluding lifetime 
AEDs, will be summarized by treatment group and overall for the SS based on the following 
categorization: 1 AEDs, 2 AEDs, and 3 AEDs. 
The number and percentage of subjects taking AEDs prior to the Baseline Period will be 
summarized by WHODD chemical subgroup (Level 4) and preferred drug name, and by 
treatment group and overall for the SS. 
Section 6.4.3 AEDs taken during the Baseline Period
The number and percentage of subjects taking AEDs during the Baseline Period defined as 
AEDs with a start date on or after the date of informed consent and prior to the first dose of study 
medication, and AEDs with a start date prior to the date of informed consent and with a stop date 
on or after the start of the Baseline Period, will be summarized, separately, by WHODD 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 74 of 96
chemical subgroup (Level 4) and preferred drug name, and by treatment group and overall for 
the SS. 
Section 6.4.4 Concomitant AEDs
The number and percentage of subjects taking concomitant AEDs defined as AEDs taken 
concomitantly for at least one day in common with study medication will be summarized, 
separately, by WHODD chemical subgroup (Level 4) and preferred drug name, and by treatment 
group and overall for the SS.
Vagus nerve stimulation is allowed and will not be counted as a concomitant AED.
Section 6.4.5 Non-AEDs taken prior to the Baseline Period
The number and percentage of subjects taking non-AEDs prior to the Baseline Period defined as 
medications with a start date prior to the date of informed consent, ie, prior to entry into the 
Baseline Period, will be summarized by WHODD anatomical main group (Level 1) and 
therapeutic subgroup (Level 2), and by treatment group and overall for the SS. 
Section 6.4.6 Non-AEDs taken during the Baseline Period
The number and percentage of subjects taking  non-AEDs during the Baseline Period defined as 
medications with a start date on or after the date of informed consent and prior to the first dose of 
study medication, and medications with a start date prior to the date of informed consent and 
with a stop date on or after the start of the Baseline Period, will be summarized by WHODD 
anatomical main group (Level 1) and therapeutic subgroup (Level 2), and by treatment group and 
overall for the SS.
Section 6.4.7 Concomitant Non-AEDs
The number and percentage of subjects taking concomitant non-AEDs defined as medications 
taken concomitantly for at least one day in common with study medication will be summarized 
by WHODD anatomical main group (Level 1) and therapeutic subgroup (Level 2), and by 
treatment group and overall for the SS.
Change #19
Section 8.1.1 Derivations of primary efficacy variable
The primary efficacy variable is the change in partial-onset seizure frequency per 28 days from 
Baseline to the Maintenance Period. 
Has been changed to:
The primary efficacy variable is the change in partial-onset seizure frequency per 28 days from 
Baseline to the Maintenance Period. Seizure frequency per 28 days will be based on the number 
of days for which seizure information was provided during the specified time interval.
Change #20
Section 8.2.7 Change in partial-onset seizure frequency per 28 days from Baseline to the 
entire Treatment Period by seizure type
In addition, descriptive statistics for change and percent change in seizure frequency per 28 days 
from Baseline to each post-Baseline visit during the entire Treatment Period will be presented by 
treatment group and seizure type.  
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 75 of 96
Has been changed to:
In addition, descriptive statistics for change and percent change in seizure frequency per 28 days 
from Baseline to each post-Baseline visit during the entire Treatment Period will be presented by 
treatment group and seizure type.  Partial-onset seizure frequency per 28 days will be presented 
graphically at each visit by treatment group, and separately at each visit by seizure type and 
treatment group. 
Change #21
Section 8.2.8 Proportion of seizure-free days during Maintenance Period
For all subjects who enter the Maintenance Period, the proportion of seizure free days during the 
Maintenance Period will be calculated.
The proportion of seizure-free days will be calculated as (days with number of seizures > 0) 
divided by (days with recorded data in the subject diary), where “days with recorded data in the 
subject diary” excludes any days where “Not Done” is recorded. 
The proportion of seizure-free days during the Maintenance Period will be summarized 
descriptively by treatment group. 
For all subjects who complete the Maintenance Period, the proportion of seizure-free days during 
the Maintenance Period will be calculated as described above, and summarized descriptively by 
treatment group.  
The change in the proportion of seizure-free days from the Baseline Period to the Maintenance 
Period will also be presented. Only subjects with efficacy data collected during the Maintenance 
Period will be included/ Statistical testing for the proportion of seizure-free days will be based on 
an ANCOVA model with terms for treatment and pooled site and a covariate of the proportion of 
seizure-free days during the Baseline Period.
The proportion of seizure-free days during the Maintenance Period will also be summarized 
using descriptive statistics by treatment group and seizure type.
Has been changed to:
For all subjects who enter the Maintenance Period, the proportion of seizure-free days during the 
Maintenance Period will be calculated.
The proportion of seizure-free days will be calculated as (days with number of seizures = 0 
during the Maintenance Period) divided by (days with recorded data in the subject diary during 
the Maintenance Period), where “days with recorded data in the subject diary” excludes any days 
where “Not Done” is recorded. 
Days with missing seizure diary information will be excluded from both the numerator and 
denominator for the seizure-free days calculation. 
For all subjects who complete the Maintenance Period, the proportion of seizure-free days during 
the Maintenance Period will be calculated as described above, and summarized descriptively by 
treatment group.  
Statistical testing for the proportion of seizure-free days during the Maintenance Period will be 
based on an ANCOVA model with terms for treatment and pooled site and a covariate of the 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 76 of 96
proportion of seizure-free days during the Baseline Period. Only Subjects with efficacy data 
collected during the Maintenance Period will be included.
The proportion of seizure-free days during the Maintenance Period will also be summarized 
using descriptive statistics by treatment group and seizure type.
Change #22
Section 8.2.9 Proportion of subjects who achieved “seizure-free” status for subjects who 
completed the Maintenance Period
A subject who completed the Maintenance Period will be defined as seizure-free if they meet the 
following criteria: 
The subject did not have any missing diary days over the Maintenance Period, that is, the seizure 
diary was completed for every day from Visit 6 to the day prior to the end date of the 
Maintenance Period. 
The subject did not report any seizures during the Maintenance Period, that is, there are no diary 
records from the day after Visit 6 (ie, not including the date of Visit 6) up to and including the 
end date of the Maintenance Period with either a count >0 or a reported seizure code with an 
unknown or missing seizure count.
The number and percentage of subjects who achieved seizure-free status during the Maintenance 
Period will be presented by treatment group.
Has been changed to:
A subject who completed the Maintenance Period will be defined as seizure-free if the subject 
did not report any seizures during the Maintenance Period, that is, there are no diary records 
during the  Maintenance Period with either a count >0 or a reported seizure code with an 
unknown or missing seizure count.
Days with missing seizure diary data will be excluded from the determination of seizure-free
status as long as the percentage of days in the Maintenance Period with missing seizure diary 
data does not exceed 20%.
The number and percentage of subjects who achieved seizure-free status during the Maintenance 
Period will be presented by treatment group.
Change #23
Section 8.3.6 Hospital stays
Hospital stays will be attributed to study periods as defined in section 3.2.2 based on admission 
date.
The number of hospital stays per subject during the Baseline Period and during the entire 
Treatment Period, separately, will be summarized by treatment group. The number of hospital 
stays will be summarized using the categories 0, 1, 2, 3, 4, and 5 or more. The number and 
percentage of subjects with specific reasons for duration of hospital stays will be summarized for 
the duration of the Baseline Period and for the duration of the entire Treatment Period, 
separately, by treatment group.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 77 of 96
Duration of hospital stays will be categorized as 0 days, 1-5 days, 6-10 days, 11-15 days, and 
>15 days, and summarized for the duration of the Baseline Period and the duration of the entire 
Treatment Period, separately, by treatment group. 
The duration of each hospital stay will be calculated as the discharge date minus the admission 
date (Hospitalization/ER Visit Date on the eCRF) plus 1 day for hospital stays with a discharge 
date. Hospitalizations with either a partial admission or discharge date are ignored for the 
calculation of duration of hospital stay. However, such hospitalizations are counted for the 
number of hospital stays. The durations of hospital stays will be summed within each of the 
study periods defined in section 3.2.2. Subjects with no hospital stays within a study period will 
have a duration of 0 days for that period. Should distinct records for hospital stays overlap, then 
the days during the overlap will only be counted once. 
All hospitalization/ER data will be listed.
Has been changed to:
Section 8.3.6 Hospital stays and emergency room visits
Hospital stays and emergency room ( ER) visits will be attributed to study periods as defined in 
section 3.2.2 based on admission date.
The number of hospital stays per subject during the Baseline Period and during the entire 
Treatment Period, separately, will be summarized by treatment group. The number of hospital 
stays will be summarized using the categories 0, 1, 2, 3, 4, and 5 or more. The number and 
percentage of subjects with specific reasons for duration of hospital stays will be summarized for 
the duration of the Baseline Period and for the duration of the entire Treatment Period, 
separately, by treatment group.
Duration of hospital stays will be categorized as 0 days, 1-5 days, 6-10 days, 11-15 days, and 
>15 days, and summarized for the duration of the Baseline Period and the duration of the entire 
Treatment Period, separately, by treatment group. 
An event logged on the Hospitalization/ER Visit eCRF module where ER is marked as the initial 
entry point will be defined as an ER visit. An ER visit with a subject transfer to an inpatient 
general ward will also be counted as a hospitalization. However, all other instances of ER visits 
(where subject transfer is not to an inpatient general ward) will not be counted as 
hospitalizations.  Descriptive statistics for the number of ER stays during the Baseline Period and 
for the duration of the entire Treatment Period, will be presented, separately, by treatment group. 
The number of ER visits will be summarized using the categories 0, 1, 2, and 3 or more. The 
number and percentage of subjects with specific resaons for duration of ER visits will be 
summarized for the duration of the Baseline Period and the duration of the entire Treatment 
Period, separately, by treatment group.
The duration of each hospital stay will be calculated as the discharge date minus the admission 
date (Hospitalization/ER Visit Date on the eCRF) plus 1 day for hospital stays with a discharge 
date. Hospitalizations with either a partial admission or discharge date are ignored for the 
calculation of duration of hospital stay. However, such hospitalizations are counted for the 
number of hospital stays. The durations of hospital stays will be summed within each of the 
study periods defined in section 3.2.2. Subjects with no hospital stays within a study period will 
have a duration of 0 days for that period. Should distinct records for hospital stays overlap, then 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 78 of 96
the days during the overlap will only be counted once. Similarly, this also applies for the ER 
visits.
All hospitalization/ER data will be listed.
Change #24
Section 10.1 Extent of exposure
All the summaries described below will also be presented for the FAS.
The overall duration of study medication exposure during each of the Titration Period, 
Maintenance Period, entire Treatment Period, Transition Period, and Taper Period (defined in 
section 3.2.2) will be calculated, as follows:
…
In addition, for the Titration Period, the number of back titration steps for each subject 
(categorized as: 0, 1-3, 4-6, and ≥7), the number of subjects with a dose change together with the 
number of dose changes during the interval by dose back titration occurred (categorized as: 
<2mg/kg/day, ≥2-<4mg/kg/day, ≥4-<6mg/kg/day, ≥6-<8mg/kg/day, ≥8-<10mg/kg/day,         
≥10-<12mg/kg/day, and ≥12mg/kg/day, <100mg/day, ≥100-<200mg/day, ≥200-<300mg/day, 
≥300-<400mg/day, and ≥400mg/day), the number of up titration steps for each subject 
(categorized as: 0, 1-3, 4-6, and ≥7), and the number of subjects with a dose change together 
with the number of dose changes during the interval by dose up titration occurred (categorized 
as: <2mg/kg/day, ≥2-<4mg/kg/day, ≥4-<6mg/kg/day, ≥6-<8mg/kg/day, ≥8-<10mg/kg/day,         
≥10-≤12mg/kg/day, and >12mg/kg/day, <100mg/day, ≥100-<200mg/day, ≥200-<300mg/day, 
≥300-<400mg/day, and ≥400mg/day), will be summarized by treatment group, and repeated by 
treatment group and age group, and by treatment group and weight group using the levels 
defined in section 4.8.
Has been changed to:
All the summaries described below will also be presented for the FAS.
The overall duration of study medication exposure during each of the Titration Period, 
Maintenance Period, entire Treatment Period, Transition Period, and Taper Period (defined in 
section 3.2.2) will be calculated, as follows:
…
In addition, for the Titration Period, the number of back titration steps for each subject 
(categorized as: 0, 1-3, 4-6, and ≥7), the number of subjects with a dose change together with the 
number of dose changes during the interval by dose back titration occurred (categorized as: 
<2mg/kg/day, ≥2-<4mg/kg/day, ≥4-<6mg/kg/day, ≥6-<8mg/kg/day, ≥8-<10mg/kg/day,         
≥10-≤12mg/kg/day, and >12mg/kg/day, <100mg/day, ≥100-<200mg/day, ≥200-<300mg/day, 
≥300-<400mg/day, and ≥400mg/day), the number of up titration steps for each subject 
(categorized as: 0, 1-3, 4-6, and ≥7), and the number of subjects with a dose change together 
with the number of dose changes during the interval by dose up titration occurred (categorized 
as: <2mg/kg/day, ≥2-<4mg/kg/day, ≥4-<6mg/kg/day, ≥6-<8mg/kg/day, ≥8-<10mg/kg/day,         
≥10-≤12mg/kg/day, and >12mg/kg/day, <100mg/day, ≥100-<200mg/day, ≥200-<300mg/day, 
≥300-≤400mg/day, and >400mg/day), will be summarized by treatment group, and repeated by 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 79 of 96
treatment group and age group, and by treatment group and weight group using the levels 
defined in section 4.8.
Change #25
Section 10.2 Adverse events
Treatment-emergent adverse events (TEAE) are defined as those events which start on or after 
the date of first study medication administration and within 30 days following the date of last 
study medication administration, or whose severity worsens within this time frame.
…
Other significant AEs, defined in Appendix 12 (Table 12.2), will be summarized for each 
treatment group by primary SOC and PT, and will be repeated by treatment group and weight 
group, using the levels defined in section 4.8. 
Has been changed to:
AEs will be tabulated by MedDRA SOC and MedDRA PT. The number and percentage of 
subjects 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.
AEs will be classified as pre-treatment, treatment-emergent, or post-treatment. Pre-treatment 
AEs are defined as AEs which had an onset date prior to the first study medication 
administration. Treatment-emergent adverse events (TEAE) are defined as those events which 
start on or after the date of first study medication administration and within 30 days following 
the date of last study medication administration, or whose severity worsens within this time 
frame. Post-treatment AEs are defined as AEs which had an onset date after 30 days after the last 
study medication administration.
All AEs reported during the study including pre-treatment and post-treatment AEs will be 
provided in a subject data listing.
…
Other significant AEs, defined in Appendix 12 (section 12.2), will be summarized for each 
treatment group by MedDRA primary SOC and PT, and will be repeated by treatment group and 
weight group, using the levels defined in section 4.8. 
In addition, summaries for the incidence of TEAEs overall, incidence of serious TEAEs, 
incidence of TEAEs leading to discontinuation of study medication, and incidence of other 
significant TEAEs will be repeated presenting the site and subject number of all those subjects 
experiencing each TEAE. Subject data listings will also be presented.
Change #26
Section 10.3 Clinical laboratory evaluations
Observed values of hematology, chemistry, and endocrinology parameters, and change from 
Baseline will be summarized by treatment group for all post-Baseline visits, and Last Value. 
Treatment-emergent markedly abnormal (TEMA) values are defined as those TEMA values 
which occur on or after the first study medication administration through to the end of the study. 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 80 of 96
The number and percentage of subjects with a TEMA value, TEMA low value, and TEMA high 
value will be summarized for each treatment group. Criteria for determining if a value is TEMA 
are detailed in Appendix 12. 
Has been changed to:
Observed values of hematology, chemistry, and non-gender specific endocrinology parameters 
(ie, thyroid stimulating hormone, triiodothyronine [total and serum-free], and thyroxine [total 
and serum-free]), and change from Baseline will be summarized by treatment group for all post-
Baseline visits, and Last Visit. Gender specific endocrinology parameters (ie, follicle stimulating 
hormone, luteinizing hormone, and testosterone) will be presented similarly, by treatment group 
and gender.
Treatment-emergent markedly abnormal (TEMA) values are defined as those TEMA values 
which occur during the defined Treatment Period (see Section 3.2.2) at scheduled or unscheduled 
visits on or after the first study medication administration through to the end of the Treatment 
Period. 
The number and percentage of subjects with a TEMA value, TEMA low value, and TEMA high 
value will be summarized for each treatment group at each post-Baseline visit and Last Visit. 
Percentages will be relative to the number of subjects with a value at each visit. Criteria for 
determining if a value is TEMA are detailed in Appendix 12.1. 
Change #27
Section 10.4.1 Vital signs, body weight, height, BMI, and head circumference
Treatment-emergent markedly abnormal (TEMA) values are defined as those TEMA values 
which occur on or after the first study medication administration through to the end of the study. 
The number and percentage of subjects with a TEMA value, TEMA low value, and TEMA high 
value, at each post-Baseline visit up to Visit 8, for which SBP, DBP, pulse rate, and body weight 
were scheduled to be assessed, and Last Value, will be presented. Percentages will be relative to 
the number of subjects with a value at each time point.
Has been changed to:
Markedly abnormal (MA) values are defined as those MA values which occur during the defined 
Treatment Period (see Section 3.2.2) at scheduled or unscheduled visits on or after the first study 
medication administration through to the end of the Treatment Period. 
The number and percentage of subjects with a MA value, MA low value, and MA high value, at 
each post-Baseline visit up to Visit 8, for which SBP, DBP, pulse rate, and body weight were 
scheduled to be assessed, and Last Visit, will be presented. Percentages will be relative to the 
number of subjects with a value at each visit. 
Also changed is the vital signs abnormality criteria table is now numbered 10-1. 
Change #28
Section 10.4.2 Electrocardiograms
Electrocardiograms will be reviewed locally and at a central ECG laboratory. If any abnormal 
finding is assessed by the investigator to be clinically significant, then the ECG should be 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 81 of 96
repeated on the same day. If the clinically significant abnormality is confirmed by the repeat 
ECG, then the subject must be withdrawn from the study. The Investigator will determine 
whether the results of the ECG are normal or abnormal and assess the clinical significance of any 
abnormalities.
The average of the 2 interpretable readings will be used for summaries. Change from Baseline in 
ECG results will be summarized for all visits, and Last Value by treatment group, and will be 
repeated by treatment group and age group, and by treatment group and weight group using the 
levels defined in section 4.8.
The number and percentage of subjects with no abnormality, an abnormal but not clinically
significant finding, and a clinically significant finding, will be summarized by treatment group at 
Visit 1 (entry to the study), Visit 2 (Baseline), and at each post-Baseline visit up to Visit 8, and 
Last Value. Percentages will be relative to the number of subjects with an ECG assessment at 
each time point. Subjects are counted at most once at each time point based on the worst 
observed outcome across all abnormalities reported at that time point.
Summaries of shifts from Baseline to post-Baseline visits, and from Baseline to Last Value, will 
also be provided by treatment group based on the categories normal, abnormal, not clinically 
significant, and abnormal, clinically significant.
A listing of ECG data will be provided for all subjects with other significant AEs in the Cardiac 
and ECG Related Terms category defined in Appendix 12 (Table 12.2). A subject data listing of 
all ECG parameter values for all subjects will also be presented. Listings will include results 
from each recording and the average of the 2 recordings. 
Has been changed to:
Electrocardiograms will be reviewed locally and at a central ECG laboratory. If any abnormal 
finding is assessed by the investigator to be clinically significant, then the ECG should be 
repeated on the same day. If the clinically significant abnormality is confirmed by the repeat 
ECG, then the subject must be withdrawn from the study. The Investigator will determine 
whether the results of the ECG are normal or abnormal and assess the clinical significance of any 
abnormalities.
For ECGs, Baseline will be defined as the average of all pre-dose interpretable readings. For all 
post-Baseline visits, the average of all interpretable readings at the specified visit will be used for 
summaries. 
Observed values of ECG results will be summarized for each visit and Last Visit. Change from 
Baseline in ECG results will be summarized for all post-Baseline visits, and Last Visit by 
treatment group, and will be repeated by treatment group and age group, and by treatment group 
and weight group using the levels defined in section 4.8.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 82 of 96
The number and percentage of subjects with no abnormality, an abnormal but not clinically 
significant finding, and a clinically significant finding, will be summarized by treatment group at 
Visit 1 (entry to the study), Visit 2 (Baseline), and at each post-Baseline visit up to Visit 8, and 
Last Visit. Percentages will be relative to the number of subjects with an ECG assessment at 
each time point. Subjects are counted at most once at each time point based on the worst 
observed outcome across all abnormalities reported at that time point.
Summaries of shifts from Baseline to post-Baseline visits, and from Baseline to Last Visit, will 
also be provided by treatment group based on the categories normal, abnormal, not clinically 
significant, and abnormal, clinically significant.
A listing of ECG data will be provided for all subjects with other significant TEAEs in the 
Cardiac and ECG Related Terms category defined in Appendix 12 (section 12.2). A subject data 
listing of all ECG parameter values for all subjects will also be presented. Listings will include 
results from each recording and the average of all recordings. 
Also changed is the electrocardiogram abnormality criteria table is now numbered 10-2. 
Change #29
Section 10.4.6 Tanner stage assessment
A shift table will be produced showing the change in Tanner stage (1-5) from Baseline to Last 
Value, by sex and treatment group, for each of the 3-items. 
Has been changed to:
A shift table will be produced showing the change in overall Tanner stage (1-5) from Baseline to 
Last Visit, by sex and treatment group. 
Change #30
Section 10.4.9.1 BRIEF-P scores
The BRIEF-P form comprises 63 questions with entry options N (never: scored as 1 point), S 
(sometimes: scored as 2 points), and O (often: scored as 3 points).
The 63 items are included in the raw Global Executive Composite (GEC) score which ranges 
from 63 to 189, with higher scores reflecting poorer functioning.
The 3 subscale scores and 5 individual component scores that make up these subscale scores are 
outlined in Table 10‒5.
Table 10-5: BRIEF-P questionnaire scoring
Scale/Index
Questions
Inhibit
3, 8, 13, 18, 23, 28, 33, 38, 43, 48, 52, 54, 56, 58, 
60, 62
Shift
5,10, 15, 20, 25, 30, 35, 40, 45, 50
Emotional Control
1, 6, 11, 16, 21, 26, 31, 36, 41, 46
BRI
All from {Inhibit, Shift and Emotional Control}
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 83 of 96
Working Memory
2, 7, 12, 17, 22, 27, 32, 37, 42, 47, 51, 53, 55, 57, 
59, 61, 63
Plan/Organize
4, 9, 14, 19, 24, 29, 34, 39, 44, 49
MI
All from {Working Memory and Plan/Organize}
GEC Score
1-63
BRI=Behavioral Regulation Index, MI=Metacognition Index, GEC=Global Executive Composite
Standardized T-scores are determined from each subject’s raw GEC, BRI, MI, and component 
scores based on the subject’s age and sex. Tables that map each raw score to the appropriate T-
score are provided in the BRIEF-P Professional Manual and will be reproduced 
programmatically.
Two validity scales will also be derived: Negativity to assess the extent to which the respondent 
answers selected BRIEF-P items in an unusually negative manner and Inconsistency to assess the 
extent to which the respondent answers similar BRIEF-P items in an inconsistent manner. The 
Negativity scale is the number of items in 30, 44, 46, 47, 53, 55, 56, 57, 59 and 63 with a score 
of 3, and so has a range of 0 to10. A score of 2 or less is considered acceptable, 3 as elevated and 
4 or more highly elevated.
For the Inconsistency scale, there are 10 item pairs of related questions. The Inconsistency scale 
is the sum of the absolute values of the difference in scores for the items in each item pair, and so 
ranges from 0 to 20. The item pairs are questions 1 and 11, 3 and 33, 5 and 45, 10 and 20, 11 and 
26, 16 and 21, 18 and 52, 33 and 38, 43 and 52, and 48 and 54. A score of 7 or less is acceptable 
and 8 or more inconsistent. 
Calculated T-score values and change from Baseline for the 2 indexed scores (BRI and MI), and 
GEC for the BRIEF-P questionnaire will be summarized at Visit 8, and Last Value, by treatment 
group. 
All BRIEF-P assessment data will be listed.
Has been changed to:
The BRIEF-P form comprises 63 questions with entry options N (never: scored as 1 point), S 
(sometimes: scored as 2 points), and O (often: scored as 3 points).
The 63 items are included in the raw Global Executive Composite (GEC) score which ranges 
from 63 to 189, with higher scores reflecting poorer functioning.
The 3 subscale scores and 5 individual component scores that make up these subscale scores are 
outlined in Table 10‒5.
Table 10-5: BRIEF-P questionnaire scoring
Scale/Index
Questions
Inhibit
3, 8, 13, 18, 23, 28, 33, 38, 43, 48, 52, 54, 56, 58, 
60, 62
Shift
5,10, 15, 20, 25, 30, 35, 40, 45, 50
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 84 of 96
Emotional Control
1, 6, 11, 16, 21, 26, 31, 36, 41, 46
Inhibitory self-control
All from {Inhibit and Emotional Control}
Flexibility
All from {Shift and Emotional Control}
Working Memory
2, 7, 12, 17, 22, 27, 32, 37, 42, 47, 51, 53, 55, 57, 
59, 61, 63
Plan/Organize
4, 9, 14, 19, 24, 29, 34, 39, 44, 49
Emergent metacognition
All from {Working Memory and Plan/Organize}
GEC Score
1-63
GEC=Global Executive Composite
Standardized T-scores are determined from each subject’s raw GEC, inhibitory self-control, 
flexibility, emergent metacognition, and component scores based on the subject’s age and sex. 
Tables that map each raw score to the appropriate T-score are provided in the BRIEF-P 
Professional Manual and will be reproduced programmatically.
Calculated T-score values and change from Baseline for the 3 indexed scores  and GEC for the 
BRIEF-P questionnaire will be summarized at Visit 8, and Last Visit, by treatment group. 
All BRIEF-P assessment data will be listed.
Change #31
Section 10.4.9.2 BRIEF scores
Standardized T-scores are determined from each subject’s raw GEC, BRI, MI, and component 
scores based on the subject’s age and sex. Tables that map each raw score to the appropriate T-
score are provided in the BRIEF Professional Manual and will be reproduced programmatically.
Two validity scales will also be derived: Negativity to assess the extent to which the respondent 
answers selected BRIEF items in an unusually negative manner, and Inconsistency to assess the 
extent to which the respondent answers similar BRIEF items in an inconsistent manner. The 
Negativity scale is the number of items in 8, 13, 23, 30, 62, 71, 80, 83, and 85 with a score of 3, 
and so has a range of 0 to 9. A score of 4 or less is considered acceptable, 5and 6 elevated and 7 
or more highly elevated.
For the Inconsistency scale, there are 10 item pairs of related questions. The Inconsistency scale 
is the sum of the absolute values of the difference in scores for the items in each item pair, and so 
ranges from 0 to 20. The item pairs are questions 7 and 25, 11 and 22, 27 and 17, 33 and 32, 38 
and 59, 41 and 65, 42 and 63, 44 and 54, 43 and 60, and 55 and 44. A score of 6 or less is 
acceptable, 7 and 8 questionable, and 9 or more inconsistent.
Calculated T-score values and change from Baseline for the 2 indexed scores (BRI and MI), and 
GEC for the BRIEF questionnaire will be summarized at Visit 8, and Last Value, by treatment 
group. 
All BRIEF assessment data will be listed.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 85 of 96
Has been changed to:
Standardized T-scores are determined from each subject’s raw GEC, BRI, MI, and component 
scores based on the subject’s age and sex. Tables that map each raw score to the appropriate T-
score are provided in the BRIEF Professional Manual and will be reproduced programmatically.
Calculated T-score values and change from Baseline for the 2 indexed scores (BRI and MI), and 
GEC for the BRIEF questionnaire will be summarized at Visit 8, and Last Visit, by treatment 
group. 
All BRIEF assessment data will be listed.
Change #32
Section 10.4 Vital signs, physical findings, and other observations related to safety
The table Vital Signs Abnormality Criteria is numbered Table 10-1.
The table Electrocardiogram Abnormality Criteria is numbered Table 10-2.
The CBCL/1½-5 table is renumbered from Table 10-1 to Table 10-3
The CBCL/6-18 table is renumbered from Table 10-2 to Table 10-4
13.2
Amendment 2
The primary purpose of this amendment is to address comments raised during and after the 
DEM#2 and DEM#3.
Change #1
Section 2.4.1 Blinded sample size re-estimation procedure
After 50% of subjects have been randomized, completed the study (including those who 
discontinued), and have Baseline and post-Baseline seizure data available for analysis, a sample 
size re-estimation procedure will be performed in 2 consecutive stages of adjustment:

Stage 1: Initial sample size re-estimation. An initial sample size re-estimation with equal 
allocation in each treatment arm will be performed using the related residual variance 
combined with Guenther adjustment (Friede and Kieser, 2011) to give a revised sample 
size to be adjusted in Stage 2 and Stage 3. This value will not be adjusted by more than 
10% above the current estimate of 135 subjects per treatment arm (ie, the initial sample 
size re-estimate will not be adjusted above 149 subjects per treatment arm).

Stage 2: Adjustment for drop-out rate. The overall study drop-out rate will be determined. 
The current SP0969 protocol plans for a 14% overall study drop-out rate for use in 
determination of sample size. If the actual overall study drop-out rate is >14%, UCB 
plans to adjust the sample size from Stage 1 accordingly, using an overall study drop-out 
rate up to a maximum of 24% (ie, the original estimated overall study drop-out rate can 
be increased by a maximum of 10%). 
After completion of the 2 stages of sample-size re-estimation, the team will update the SP0969 
protocol accordingly. UCB does not plan to reduce the sample size as a result of the blinded 
sample size re-estimation.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 86 of 96
Has been changed to:
After 50% of subjects have been randomized, completed the study (including those who 
discontinued), and have Baseline and post-Baseline seizure data available for analysis, a sample 
size re-estimation procedure will be performed in 2 consecutive stages of adjustment:

Stage 1: Initial sample size re-estimation. An initial sample size re-estimation with equal 
allocation in each treatment arm will be performed using the related residual variance 
combined with Guenther adjustment (Friede and Kieser, 2011) to give a revised sample 
size to be adjusted in Stage 2 and Stage 3. This value will not be adjusted by more than 
10% above the current estimate of 135 subjects per treatment arm (ie, the initial sample 
size re-estimate will not be adjusted above 149 subjects per treatment arm).

Stage 2: Adjustment for drop-out rate. The overall study drop-out rate will be determined. 
The current SP0969 protocol plans for a 14% overall study drop-out rate for use in 
determination of sample size. If the actual overall study drop-out rate is >14%, UCB 
plans to adjust the sample size from Stage 1 accordingly, using an overall study drop-out 
rate up to a maximum of 24% (ie, the original estimated overall study drop-out rate can 
be increased by a maximum of 10%). 
Change #2
Section 3.2.2 Study periods
Maintenance Period
The day after the end of the Titration Period (Visit 5) and prior to or on the end date of the 
Maintenance Period (Visit 8) for subjects who complete the Maintenance Period, or on or after 
the date of first dose of study medication and prior to or on the date of the ETV for subjects who 
discontinue during the Maintenance Period. If a subject does not have a Visit 8/ETV, then either 
the date of the last scheduled or unscheduled visit during the Maintenance Period or the date of 
last known dose of study medication during the Maintenance Period, whichever is later, will 
define the end date of the Maintenance Period.
Has been changed to:
Maintenance Period
The day after the end of the Titration Period (Visit 5) and prior to or on the end date of the 
Maintenance Period (Visit 8) for subjects who complete the Maintenance Period, or the day after 
the end of the Titration Period (Visit 5) and prior to or on the date of the ETV for subjects who 
discontinue during the Maintenance Period. If a subject does not have a Visit 8/ETV, then either 
the date of the last scheduled or unscheduled visit during the Maintenance Period or the date of 
last known dose of study medication during the Maintenance Period, whichever is later, will 
define the end date of the Maintenance Period.
Change #3
Section 3.5.3 Per Protocol Set
The PPS includes all subjects in the FAS who did not have important protocol deviations. 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 87 of 96
Has been changed to:
The PPS includes all subjects in the FAS who did not have important protocol deviations 
considered to have an impact on efficacy as confirmed during a DEM conducted prior to study 
unblinding.
Change #4
Section 3.7 Center pooling strategy
It is planned to appropriately pool centers by geographic location. The final strategy for pooling 
will be determined at the DEM.
Has been changed to:
All centers will be pooled by country for the purpose of analysis.
Change #5
Section 4.2.3 Definition of concomitant medication in case of missing dates
With respect to definition of medication as concomitant, the following rule will be applied in 
case of completely missing stop and/or start date information: 
Medications with a missing start date whose stop date is either unknown or after the date of the 
first dose of study medication will be considered as concomitant medication. 
Medications with a missing start date whose stop date is prior to first intake of study medication 
will not be considered concomitant.
In subject data listings, dates will be displayed as reported.
Has been changed to:
With respect to definition of medication as concomitant, the following rule will be applied in 
case of completely missing stop and/or start date information: 
Medications, excluding AEDs, with a missing start date whose stop date is either unknown or 
after the date of the first dose of study medication will be considered as concomitant medication. 
AEDs with a missing start date whose stop date is unknown will be considered as lifetime AEDs. 
AEDs with a missing start date whose stop date is after the date of first dose of study medication 
will be considered concomitant.
Medications, including AEDS, with a missing start date whose stop date is prior to first intake of
study medication will not be considered concomitant.
In subject data listings, dates will be displayed as reported.
Change #6
Section 6.4.1 Number of Lifetime AEDs
The number of lifetime AEDs defined as AEDs taken and stopped >28 days prior to Visit 1 (ie, 
prior to entry into the Baseline Period), will be summarized by treatment group and overall for 
the SS based on the following categorization: 1 to 3 AEDs, 4-6 AEDs, and ≥7 AEDs. 
Has been changed to:
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 88 of 96
The number of lifetime AEDs defined as AEDs taken and stopped >28 days prior to Visit 1 (ie, 
prior to entry into the Baseline Period), or AEDs with a missing start date and unknown stop 
date, will be summarized by treatment group and overall for the SS based on the following 
categorization: 0 AEDs, 1 to 3 AEDs, 4-6 AEDs, and ≥7 AEDs. 
Change #7
Added new Section 6.4.4, so subsequent sections have been renumbered.
Section 6.4.4 Number of AEDs taken on day of first dose of study medication
The number of AEDs taken on the day of first dose of study medication will be summarized by 
treatment group and overall for the SS based on the following categorization: 1 AED, 2 AEDs, 
and 3 AEDs.
Change #8
Section 7 Measurements of treatment compliance
Actual weight of study medication used
Actual weight of study medication will be determined for each visit. The weight used will be 
computed by comparing the weight of the bottles (including adaptors and caps) of oral solution 
at dispensation to their weight upon return.
Actual weight of study medication oral solution will be calculated at each visit using the 
following formula:
Actual weight of used oral solution (g) = Total weight of bottles (including adapters and caps) at 
Dispensation - Total weight of bottles (including adapters and caps) at Return
The actual weight used will also be determined for the Titration Period, Maintenance Period, and 
the entire Treatment Period (Titration+Maintenance Periods). 
Expected weight of study medication used
Expected weight of study medication will be determined for each visit. The expected weight will 
be based on the actual number of days between visits, and the prescribed daily dosing of study 
medication oral solution.
The following formula will be used to calculate the expected weight of oral solution for the 
respective study medication dose:
Expected weight of used oral solution (g) = Daily prescribed oral solution (mL) x Number of 
days between visit x 1.1g/mL. Please note that the estimated weight of 1mL of LCM is 1.1g.
The expected weight will also be determined for the Titration Period, Maintenance Period, and 
the entire Treatment Period (Titration+Maintenance Periods). 
Compliance
A subject’s dosing compliance should be within 75-125% during each visit. Compliance to study 
medication dosing will be calculated for each visit, and will also be determined for the Titration 
Period, Maintenance Period, and the entire Treatment Period (Titration+Maintenance Periods). 
For oral solution, compliance will be calculated using the following formula:
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 89 of 96
Compliance (%) = Actual weight of used oral solution (g) / Expected weight of used oral 
solution (g) x 100
For tablets, compliance will be calculated using the following formula:
Compliance (%) = (Number of tablets dispensed – Number of tablets returned) / (Number of 
tablets prescribed per day (2 tablets) x Number of days between visit)) x 100
Has been changed to:
The total weight of used oral solution (mg) will be calculated as:
(Sum of actual weight of used oral solution [g] / 1.1g/mL) x 10mg/mL
Note that the estimated weight of 1mL of oral solution is 1.1g, and the concentration is 
10mg/mL.
Where:
Actual weight of used oral solution (g) = Total weight of bottles (including adaptors and 
caps) at Dispensation - Total weight of bottles (including adaptors and caps) at Return
The expected weight of used oral solution (mg) will be calculated as:
Sum of daily oral solution (mg) for each day in the corresponding time period
Where: 
Daily oral solution (mg) = (Morning dose [mg/kg] + Evening dose [mg/kg])  x Baseline 
weight (kg)
Total amount of tablets (mg) will be calculated as:
(100 x [number of 100 mg tablets dispensed – number of 100 mg tablets returned] + 50 x 
[number of 50 mg tablets dispensed – number of 50 mg tablets returned])
Expected amount of tablets (mg) will be calculated as:
Sum of daily tablets (mg) for each day in the corresponding time period
Where: 
Daily tablets (mg) = Morning dose (mg) + Evening dose (mg)
Compliance
Compliance during a time period will be calculated using data from the respective time period 
only as follows:
100 x (Total weight of used oral solution [mg] + Total amount of tablets used [mg]) / (expected 
weight of used oral solution [mg] + expected amount of tablets [mg])
A subject’s dosing compliance should be within 75-125% during each visit. Compliance to study 
medication dosing will be calculated for each visit, and will also be determined for the Titration 
Period, Maintenance Period, and the entire Treatment Period (Titration+Maintenance Periods).
Compliance will be summarized separately for the Titration Period, Maintenance Period, and 
entire Treatment Period for the SS. It will be presented using descriptive statistics and 
additionally using the categorization <75%, ≥75% to ≤125%, and >125%.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 90 of 96
Change #9
Section 8.1.1 Derivations of primary efficacy variable
The primary efficacy variable is the change in partial-onset seizure frequency per 28 days from 
Baseline to the Maintenance Period. Seizure frequency per 28 days will be based on the number 
of days for which seizure information was provided during the specified time interval.
Seizure frequency per 28 days will be calculated as ([number of seizures over the specified time 
interval] divided by [number of days in the interval]) multiplied by 28.
The partial-onset seizure frequency per 28 days will be calculated for both the Baseline Period 
and for the Maintenance Period, and the change from Baseline calculated. 
Has been changed to:
The primary efficacy variable is the change in partial-onset seizure frequency per 28 days from 
Baseline to the Maintenance Period. Seizure frequency per 28 days will be based on the number 
of days for which seizure information was provided during the specified time interval.
Seizure frequency per 28 days will be calculated as ([number of seizures over the specified time 
interval] divided by [number of days in the interval]) multiplied by 28.
The partial-onset seizure frequency per 28 days will be calculated for both the Baseline Period 
and for the Maintenance Period, and the change from Baseline calculated. 
If a seizure cluster is reported, the highest recorded daily seizure frequency during the Treatment 
Period for the seizure type associated with the report of a seizure cluster will be used as the 
imputed seizure frequency for the day on which the cluster occurred.
Change #10
Section 8.1.2 Primary analysis of the primary efficacy variable 
Seizure frequency will be analyzed using analysis of covariance with terms for treatment and 
center (pooled appropriately), on log-transformed seizure frequency using the transformation of 
ln(X+1), where X is the seizure frequency. Log transformed Baseline seizure frequency will be 
used as a covariate. The seizure frequency between treatment and placebo will be compared 
using the least squares means (LSMs). The percent reduction over placebo will be estimated as 
100 x (1 – exp [LSM LCM – LSM placebo]). A 95% CI will also be calculated for the percent 
reduction over placebo. 
Partial-onset seizure frequency per 28 days during the Baseline Period and during the 
Maintenance Period, and the change from Baseline will be summarized by treatment group. This 
summary will be repeated by treatment group and age group, using the levels defined in section 
4.8.
Has been changed to:
Seizure frequency will be analyzed using analysis of covariance (ANCOVA) with terms for 
treatment and center (pooled appropriately), on log-transformed seizure frequency using the 
transformation of ln(X+1), where X is the seizure frequency. Log transformed Baseline seizure 
frequency will be used as a covariate. Assumptions for the parametric model will be evaluated by 
diagnostic (eg, Shapiro-Wilk test for normality) and graphical methods such as residual plots, 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 91 of 96
including normal probability plots, histograms, and plots of residuals versus Baseline covariate 
values and treatment. An assessment will be made with regards to the influence of individual 
observations (eg, extreme outliers) on the analysis. To the extent feasible, such potential 
influential observations will be identified prior to unblinding, and an assessment will be made 
with regard to the potential impact of such data, including the evaluation of alternative statistical 
methodology such as non-parametric methods. If deemed that a non-parametric method is 
warranted, an ANCOVA model on rank of seizure frequency per 28 days with terms for 
treatment and center (pooled appropriately) will be employed as the primary analysis. Ranked 
seizure frequency per 28 days during the Baseline Period will be used as a covariate. 
The seizure frequency between treatment and placebo will be compared using the least squares 
means (LSMs). The percent reduction over placebo will be estimated as 100 x (1 – exp [LSM 
LCM – LSM placebo]). A 95% CI will also be calculated for the percent reduction over placebo. 
Partial-onset seizure frequency per 28 days during the Baseline Period and during the 
Maintenance Period, and the change from Baseline will be summarized by treatment group. This 
summary will be repeated by treatment group and age group, using the levels defined in section 
4.8.
Change #11
Section 8.3.3 PedsQL assessment 
The above algorithm will also be used to calculate an overall total scale score (all scales) for 
each subject.
Calculated values and change from Baseline for the total scale score and each of the 4 scale 
scores will be summarized for each visit and Last Visit by treatment group. Subgroup summaries 
by age will be performed using the age groupings for which different questionnaires were 
entered: ≥2 to ≤4 years, ≥5 to ≤7 years, ≥8 to ≤12 years, and ≥13 to ≤18 years.
Has been changed to:
The above algorithm will also be used to calculate an overall Total Scale Score (all scales) and 
the Psychosocial Health Summary Score (a combination of the emotional, social and school 
functioning questions) for each subject.
Calculated values and change from Baseline for the total scale score, psychosocial health score 
and each of the 4 scale scores will be summarized for each visit and Last Visit by treatment 
group. Subgroup summaries by age will be performed using the age groupings for which 
different questionnaires were entered: ≥2 to ≤4 years, ≥5 to ≤7 years, ≥8 to ≤12 years, and ≥13 to 
≤18 years.
Change #12
Section 9.1 Descriptive statistics of LCM and AED plasma concentrations 
The results of LCM and other AEDs plasma concentrations will be described by the method of 
descriptive statistics: arithmetic mean, SD, median, range, geometric mean, and geometric CV. 
The evaluations will be done based on separation by LCM maintenance dose level, and repeated 
by LCM maintenance dose level and age group.
Has been changed to:
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 92 of 96
The results of LCM and other AEDs plasma concentrations will be described by the method of 
descriptive statistics: arithmetic mean, SD, median, range, geometric mean, and geometric CV. 
The evaluations will be done based on separation by LCM maintenance dose level, and repeated 
by LCM maintenance dose level and age group.
Summarization of PK data relative to time after dose will be performed for the overall group and 
separated by AED therapy and possibly age groups.
Change #13
Section 9.2 Population pharmacokinetics 
Summarization of PK data relative to time after dose will be performed for the overall group and 
separated by AED therapy and possibly age groups.
A population PK modeling of the LCM concentration time data will be performed within the 
NONMEM software. The effects of age, body weight, AED therapy, and other covariates will be 
evaluated. Simulations will be undertaken for estimating dose adaptations leading to the same 
exposure as in adults. 
The methods will be described in the Data Analysis Plan (DAP) and the results will be reported 
in a separate modeling report.
Has been changed to:
A population PK modeling of the LCM concentration time data will be performed within the 
NONMEM software. The effects of age, body weight, AED therapy, and other covariates will be 
evaluated. Simulations will be undertaken for estimating dose adaptations leading to the same 
exposure as in adults. 
The methods will be described in the Data Analysis Plan (DAP) and the results will be reported 
in a separate modeling report.
Change #14
Section 10.1 Extent of exposure 
All the summaries described below will also be presented for the FAS.
The overall duration of study medication exposure during each of the Titration Period, 
Maintenance Period, entire Treatment Period, Transition Period, and Taper Period (defined in 
section 3.2.2) will be calculated, as follows:
Titration Period: date of last dose of study medication during the Titration Period minus the date 
of first dose of study medication plus 1.
Maintenance Period: date of last dose of study medication during the Maintenance Period minus 
the date of first dose of study medication during the Maintenance Period plus 1. 
Entire Treatment Period: date of last dose of study medication during the entire Treatment Period 
minus the date of first dose of study medication plus 1.
Transition Period: date of last dose of study medication during the Transition Period minus the 
date of first dose of study medication during the Transition Period plus 1. 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 93 of 96
Taper Period: date of last dose of study medication during the Taper Period minus the date of 
first dose of study medication during the Taper Period plus 1. 
Entire study: date of final dose of study medication minus the date of first dose of study
medication plus 1.
The overall duration of study medication exposure will be summarized for each of the study 
periods defined above, and also for the entire study by treatment group, and repeated by 
treatment group and age group, and by treatment group and weight group using the levels 
defined in section 4.8. 
In addition, the overall duration of study medication exposure will be summarized using the 
following categories for each of the study periods defined above, and also for the entire study by 
treatment group, and repeated by treatment group and age group, and by treatment group and 
weight group using the levels defined in section 4.8:
Titration Period: ≤2 weeks, >2-≤4 weeks, and >4-≤6 weeks.
Maintenance Period: ≤2 weeks, >2-≤4 weeks, >4-≤6 weeks, >6-≤8 weeks, and >8-≤10 weeks.
Entire Treatment Period: ≤2 weeks, >2-≤4 weeks, >4-≤6 weeks, >6-≤8 weeks, >8-≤10 weeks, 
>10-≤12 weeks, >12-≤14 weeks, and >14- ≤16 weeks. 
Transition Period: ≤2 weeks, and >2-≤4 weeks.
Taper Period: ≤2 weeks, and >2-≤4 weeks.
Entire study: ≤2 weeks, >2-≤4 weeks, >4-≤6 weeks, >6-≤8 weeks, >8-≤10 weeks, >10-≤12 
weeks, >12-≤14 weeks, >14-≤16 weeks, >16-≤18 weeks, >18-≤20 weeks, >20-≤22 weeks, and 
>22-≤24 weeks.
Has been changed to:
The overall duration of study medication exposure during each of the Titration Period, 
Maintenance Period and entire Treatment Period (defined in section 3.2.2) will be calculated, as 
follows:
Titration Period: date of last dose of study medication during the Titration Period minus the date 
of first dose of study medication plus 1.
Maintenance Period: date of last dose of study medication during the Maintenance Period minus 
the date of first dose of study medication during the Maintenance Period plus 1. 
Entire Treatment Period: date of last dose of study medication during the entire Treatment Period 
minus the date of first dose of study medication plus 1.
The overall duration of study medication exposure will be summarized for each of the study 
periods defined above by treatment group, and repeated by treatment group and age group, and 
by treatment group and weight group using the levels defined in section 4.8. 
In addition, the overall duration of study medication exposure will be summarized using the 
following categories for each of the study periods defined above by treatment group, and 
repeated by treatment group and age group, and by treatment group and weight group using the 
levels defined in section 4.8:
Titration Period: ≤2 weeks, >2-≤4 weeks, and >4-≤6 weeks.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 94 of 96
Maintenance Period: ≤2 weeks, >2-≤4 weeks, >4-≤6 weeks, >6-≤8 weeks, and >8-≤10 weeks.
Entire Treatment Period: ≤2 weeks, >2-≤4 weeks, >4-≤6 weeks, >6-≤8 weeks, >8-≤10 weeks, 
>10-≤12 weeks, >12-≤14 weeks, and >14- ≤16 weeks. 
Change #15
Section 10.4.4.1 Complete neurological examination
…
Summaries of shift from Baseline to Last Visit will be provided by treatment group based on 
categories normal, abnormal, not clinically significant, and abnormal, clinically significant. A 
listing of neurological examination findings from the complete neurological examination will 
also be provided.
Has been changed to:
…
Summaries of shift from Baseline to Last Visit will be provided by treatment group based on 
categories normal, abnormal, not clinically significant, and abnormal, clinically significant. A 
listing of abnormal neurological examination findings from the complete neurological 
examination will also be provided.
Change #16
Section 10.4.4.1 Brief neurological examination
…
A listing of neurological examination findings from the brief neurological examination will also 
be provided. No summaries of the brief neurological examination findings are planned.
Has been changed to:
…
A listing of abnormal neurological examination findings from the brief neurological examination 
will also be provided. No summaries of the brief neurological examination findings are planned.
Change #17
Section 10.4.7 Achenbach Child Behavior Checklist
The syndrome scale “Emotionally reactive” originally had 28 as a question instead of 82.
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 95 of 96
Table 13‒3: CBCL/1½-5
Syndrome scale
Questions
Aggressive behavior
8, 15, 16, 18, 20, 27, 29, 35, 40, 42, 44, 53, 58, 66, 
69, 81, 85, 88, 96
Anxious/depressed
10, 33, 37, 43, 47, 68, 87, 90
Attention problems
5, 6, 56, 59, 95
Emotionally reactive
21, 46, 51, 79, 28, 83, 92, 97, 99
Sleep problems
22, 38, 48, 64, 74, 84, 94
Somatic complaints
1, 7, 12, 19, 24, 39, 45, 52, 78, 86, 93
Withdrawn
2, 4, 23, 62, 67, 70, 71, 98
Other problems
3, 9, 11, 13, 14, 17, 25, 26, 28, 30, 31, 32, 34, 36, 
41, 49, 50, 54, 55, 57, 60, 61, 63, 65, 72, 73, 75, 76, 
77, 80, 89, 91, 100
Has been changed to:
Table 13‒4: CBCL/1½-5
Syndrome scale
Questions
Aggressive behavior
8, 15, 16, 18, 20, 27, 29, 35, 40, 42, 44, 53, 58, 66, 
69, 81, 85, 88, 96
Anxious/depressed
10, 33, 37, 43, 47, 68, 87, 90
Attention problems
5, 6, 56, 59, 95
Emotionally reactive
21, 46, 51, 79, 82, 83, 92, 97, 99
Sleep problems
22, 38, 48, 64, 74, 84, 94
Somatic complaints
1, 7, 12, 19, 24, 39, 45, 52, 78, 86, 93
Withdrawn
2, 4, 23, 62, 67, 70, 71, 98
Other problems
3, 9, 11, 13, 14, 17, 25, 26, 28, 30, 31, 32, 34, 36, 
41, 49, 50, 54, 55, 57, 60, 61, 63, 65, 72, 73, 75, 76, 
77, 80, 89, 91, 100
Change #18
Section 12.2 Other significant adverse events
Removed the footnote from the table as this was not applied to the programming of other 
significant adverse events. 
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UCB
09 Feb 2017
Statistical Analysis Plan
Lacosamide
SP0969
Confidential
Page 96 of 96
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 Statistical Analysis Plan (SAP) or amended SAP is released for execution.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


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