Clinical trial NCT02582866
Conditions: Epilepsy
Keywords: Lacosamide Vimpat Epilepsy Partial onset seizures Tonic-clonic seizures Monotherapy AED
Sponsor: UCB Biopharma S.P.R.L.
Start date: 2016-01-01; Completion date: 2020-01-01
Enrollment: 106 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Study is conducted to evaluate the long-term safety and tolerability of lacosamide (LCM) in patients receiving LCM in SP0994 \[NCT01465997\]. The study will enable collection of additional monotherapy safety data, and will facilitate access to treatment until commercial availability for monotherapy use.

Detailed description:

Arms: arm 1: Lacosamide (LCM) will be administered orally twice daily from 200 mg/day to 600 mg/day (at approximately 12 hour intervals in the morning and in the evening) in 2 divided doses. Medication must not be chewed and must be swallowed with a sufficient amount of fluid. The investigator may maintain the subject's LCM dose, decrease the dose in decrements of 100 mg/day per week to a minimum dose of LCM 200 mg/day, or increase the dose in increments of 100 mg/day per week up to a maximum dose of LCM 600 mg/day.

Subjects stopping LCM should be tapered off LCM at recommended decreasing steps of 200 mg/day/week. A slower taper (eg, 100 mg/day/week) or faster taper is permitted, if medically necessary; however, the maximum duration of tapering should not exceed 6 weeks.
Interventions: intervention 1: Lacosamide
Intervention descriptions: intervention 1: * Pharmaceutical Form: Oral tablets
* Concentration: 50 mg
* Route of Administration: Oral administration

Protocol documents:
Prot_000.pdf: 
UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 1 of 48
PROTOCOL SP1042 AMENDMENT 1
A MULTICENTER, OPEN-LABEL, FOLLOW-UP STUDY TO 
ASSESS THE LONG-TERM USE OF LACOSAMIDE (FLEXIBLE 
DOSE FROM 200 TO 600MG/DAY) USED AS MONOTHERAPY 
IN SUBJECTS WHO COMPLETED SP0994 AND RECEIVED 
LACOSAMIDE MONOTHERAPY TREATMENT
PHASE 3B
EudraCT Number: 2015-001549-96
Sponsor:
UCB BioPharma SPRL
Allée de la Recherche 60
B-1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
12 May 2015
Not applicable
Protocol Amendment 1
01 Jul 2015
Nonsubstantial
Confidential Material
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 2 of 48
STUDY CONTACT INFORMATION
Sponsor
UCB BioPharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Principal/Coordinating Investigator
The Principal/Coordinating Investigator will be listed separately.
Sponsor Study Physician
Name:
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Clinical Project Manager
Name:
Address:
UCB BioPharma SPRL
Allée de la Recherche 60
B-1070 Brussels
BELGIUM
Phone:
Fax:
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 3 of 48
Clinical Trial Biostatistician
Name:
Address:
UCB BIOSCIENCES Inc.
8010 Arco Corporate Drive, Suite 100 (courier)
Raleigh, NC 27617, USA
PO Box 110167 (mail)
Research Triangle Park, NC 27709
USA
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Function:
Project management and site monitoring
Name:
PAREXEL International GmbH
Address:
Klinikum Westend, Spandauer Damm 130
14050 Berlin
GERMANY
Phone:
+49 30 30685 0
Fax:
+49 30 30685 299
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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 4 of 48
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
Email
Global: DSICT@ucb.com (for interventional clinical studies)
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 5 of 48
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................8 
1 
SUMMARY.......................................................................................................................9 
2 
INTRODUCTION ...........................................................................................................10 
3 
STUDY OBJECTIVE......................................................................................................12 
4 
STUDY VARIABLES.....................................................................................................12 
4.1 
Safety variables......................................................................................................12 
4.1.1 
Primary safety variables...............................................................................12 
5 
STUDY DESIGN.............................................................................................................12 
5.1 
Study description ...................................................................................................12 
5.1.1 
Study duration per subject ...........................................................................15 
5.1.2 
Planned number of subjects and sites ..........................................................15 
5.1.3 
Anticipated regions and countries................................................................15 
5.2 
Schedule of study assessments...............................................................................15 
5.3 
Rationale for study design and selection of dose...................................................18 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................18 
6.1 
Inclusion criteria ....................................................................................................18 
6.2 
Exclusion criteria ...................................................................................................18 
6.3 
Withdrawal criteria ................................................................................................19 
7 
STUDY TREATMENT...................................................................................................20 
7.1 
Description of investigational medicinal product..................................................20 
7.2 
Treatment to be administered.................................................................................20 
7.3 
Packaging...............................................................................................................22 
7.4 
Labeling .................................................................................................................22 
7.5 
Handling and storage requirements .......................................................................22 
7.6 
Drug accountability................................................................................................22 
7.7 
Procedures for monitoring subject compliance......................................................23 
7.8 
Concomitant medications/treatments.....................................................................23 
7.8.1 
Permitted concomitant treatments (medications and therapies) ..................23 
7.8.2 
Prohibited concomitant treatments (medications and therapies) .................23 
7.8.3 
Permitted agents to be used with caution.....................................................23 
7.9 
Blinding..................................................................................................................23 
7.10 
Randomization and numbering of subjects............................................................23 
8 
STUDY PROCEDURES BY VISIT ...............................................................................24 
8.1 
Visit 1 (Week 0).....................................................................................................24 
8.2 
Visit 2, 3, 4, 5, 6 (Week 26, 52, 78, 104, 130)-Treatment Visits...........................24 
8.3 
Early Termination Visit/Termination Visit............................................................25 
8.4 
Final Visit...............................................................................................................25 
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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
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8.5 
Unscheduled Visit..................................................................................................26 
9 
ASSESSMENT OF SAFETY..........................................................................................26 
9.1 
Adverse events.......................................................................................................26 
9.1.1 
Definition of adverse event..........................................................................26 
9.1.2 
Procedures for reporting and recording adverse events...............................26 
9.1.3 
Description of adverse events......................................................................26 
9.1.4 
Follow up of adverse events ........................................................................27 
9.1.5 
Rule for repetition of an adverse event........................................................27 
9.1.6 
Pregnancy.....................................................................................................27 
9.1.7 
Overdose of investigational medicinal product ...........................................28 
9.1.8 
Safety signal detection.................................................................................28 
9.2 
Serious adverse events ...........................................................................................28 
9.2.1 
Definition of serious adverse event .............................................................28 
9.2.2 
Procedures for reporting serious adverse events..........................................29 
9.2.3 
Follow up of serious adverse events............................................................30 
9.3 
Adverse events of special interest..........................................................................30 
9.4 
Immediate reporting of adverse events..................................................................31 
9.5 
Anticipated serious adverse events ........................................................................31 
9.6 
Laboratory measurements......................................................................................32 
9.6.1 
Liver function tests ......................................................................................32 
9.6.2 
Pregnancy testing.........................................................................................33 
10 STUDY MANAGEMENT AND ADMINISTRATION.................................................33 
10.1 
Adherence to protocol............................................................................................33 
10.2 
Monitoring .............................................................................................................33 
10.2.1 
Definition of source data..............................................................................34 
10.2.2 
Source data verification ...............................................................................34 
10.3 
Data handling.........................................................................................................34 
10.3.1 
Case Report form completion......................................................................34 
10.3.2 
Database entry and reconciliation................................................................34 
10.3.3 
Subject Screening and Enrollment log/Subject Identification Code list......35 
10.4 
Termination of the study........................................................................................35 
10.5 
Archiving and data retention..................................................................................35 
10.6 
Audit and inspection ..............................................................................................35 
10.7 
Good Clinical Practice ...........................................................................................36 
11 STATISTICS ...................................................................................................................36 
11.1 
Definition of analysis sets......................................................................................36 
11.2 
General statistical considerations...........................................................................36 
11.3 
Planned safety and other analyses..........................................................................36 
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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 7 of 48
11.3.1 
Safety analyses.............................................................................................36 
11.4 
Handling of protocol deviations.............................................................................37 
11.5 
Handling of dropouts or missing data....................................................................37 
11.6 
Planned interim analysis and data monitoring.......................................................37 
11.7 
Determination of sample size.................................................................................37 
12 ETHICS AND REGULATORY REQUIREMENTS......................................................37 
12.1 
Informed consent ...................................................................................................37 
12.2 
Subject identification cards....................................................................................38 
12.3 
Institutional Review Boards and Independent Ethics Committees........................38 
12.4 
Subject privacy.......................................................................................................39 
12.5 
Protocol amendments.............................................................................................39 
13 FINANCE, INSURANCE, AND PUBLICATION.........................................................39 
14 REFERENCES ................................................................................................................39 
15 APPENDICES .................................................................................................................41 
15.1 
Protocol Amendment 1 ..........................................................................................41 
16 DECLARATION AND SIGNATURE OF INVESTIGATOR .......................................47 
17 SPONSOR DECLARATION ..........................................................................................48 
LIST OF TABLES
Table 5‒1: Schedule of study assessments .............................................................................16 
Table 7‒1: LCM dosing schedule for Treatment Phase and End-of-Study Phase (if 
tapering is required)..............................................................................................21 
Table 9‒1: Anticipated SAEs for the adult epileptic population ............................................31 
Table 9‒2: Laboratory measurements.....................................................................................32 
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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 8 of 48
LIST OF ABBREVIATIONS
AE
adverse event
AED
antiepileptic drug
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AV
atrioventricular 
CBZ-CR
carbamazepine (controlled release)
CDMS
clinical data management system
CPM
Clinical Project Manager
CPMP
Committee for Proprietary Medicinal Products
CHMP
Committee for Medicinal Products for Human Use
CRF
Case Report form
CRO
contract research organization
DS
Drug Safety
ECG
electrocardiogram
EDC
electronic data capture
EMA/EMEA
European Medicines Agency
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IMP
investigational medicinal product
IRB
Institutional Review Board
iv
intravenous
IXRS
interactive voice/web response system
LCM
lacosamide
LFT
liver function test
MedDRA
Medical Dictionary for Regulatory Activities
PK
pharmacokinetic(s)
SAE
serious adverse event
SOP
Standard Operating Procedure
TEAE
treatment-emergent adverse event
ULN
upper limit of normal
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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 9 of 48
1
SUMMARY
SP1042 is a Phase 3B, multicenter, open-label, follow-up study evaluating the safety and 
tolerability of long-term use of lacosamide (LCM; Vimpat®, SPM 927; previously referred to as 
harkoseride; [R]-2-acetamido-N-benzyl-3-methoxypropionamide, ADD 234037) (flexible doses 
from 200 to 600mg/day), used as monotherapy in subjects ≥16 years of age with partial-onset 
seizures or generalized tonic-clonic seizures who have completed SP0994. 
Subjects treated with LCM in SP0994 will be allowed to continue the same treatment in SP1042 
until marketing application for LCM is approved and LCM is commercially available for 
monotherapy in the subject’s country, or UCB has determined that the clinical development 
program for the monotherapy indication will be formally discontinued, or up to a maximum
period of 3 years, whichever is earlier.
SP0994 is a double-blind, follow-up study to SP0993 evaluating the long-term safety and 
tolerability of LCM as compared to carbamazepine (controlled release) (CBZ-CR) and was 
designed to assess the long-term effects of LCM in accordance with European Medicines 
Agency (EMA) guidelines (CHMP/EWP/566/98, 2010). Following the database lock and 
unblinding of SP0993, SP0994 will be unblinded. The individual subject treatment (ie, LCM or 
CBZ-CR) will be made known to both the subject and the investigator. Once the program for 
follow-up access to LCM monotherapy is established, a Termination Visit will be scheduled as 
soon as possible.
SP1042 is an open-label, follow-up study evaluating the long-term safety and tolerability of 
LCM in patients receiving LCM in SP0994, and would commence after the SP0994 Termination 
Visit. SP1042 will enable collection of additional LCM monotherapy safety data in a controlled 
manner and will also facilitate access to treatment with LCM for subjects receiving LCM in 
SP0994 until commercial availability of LCM for monotherapy use.
The study will be conducted at approximately 70 sites in Europe, Latin America, Asia, and other 
regions. It is anticipated that approximately 150 subjects who receive LCM in SP0994 will 
participate in this follow-up study. 
Subjects in SP0994 who were receiving LCM will have the opportunity to participate in SP1042. 
Subjects who were receiving CBZ-CR or who were in LCM taper in SP0994 at the time of 
unblinding will not be allowed to participate in SP1042 and can continue to receive 
commercially available CBZ therapy or other commercially available treatment options (which 
will not be provided by UCB). SP1042 consists of a Treatment Phase of up to 156 weeks and an 
End-of-Study Phase of up to 8 weeks. Visit 1 for SP1042 will be the same as the Termination 
Visit of SP0994. Beginning with SP1042 Visit 1, study visits will occur at approximately 
26-week intervals through the Early Termination/Termination Visit. The Termination Visit for 
subjects in the SP1042 Treatment Phase will be performed at the time that the marketing 
application for LCM is approved and LCM is commercially available for monotherapy in the 
subject’s country, or UCB has determined that the clinical development program for the 
monotherapy indication will be formally discontinued, or up to a maximum period of 3 years, 
whichever is earlier. Subjects may be immediately prescribed commercially available LCM. 
Subjects who do not wish to continue LCM at the end of the study will be tapered off LCM. A 
Final Visit will occur 2 weeks after the final dose of LCM.
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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 10 of 48
The individual starting dose in SP1042 for each subject will be the same dose reached at the end 
of SP0994 (LCM 200mg/day, 300mg/day, 400mg/day, 500mg/day, or 600mg/day). During 
SP1042, investigators will be allowed to increase or decrease the dose of LCM to optimize 
tolerability and seizure reduction for each subject based upon individual subject response. The 
investigator may maintain the subject’s LCM dose, decrease the dose in decrements of 
100mg/day per week to a minimum dose of LCM 200mg/day, or increase the dose in increments 
of 100mg/day per week up to a maximum dose of LCM 600mg/day. Lacosamide doses 
administered in this study must be from 200mg/day to 600mg/day, must comply with doses that 
can be administered with LCM 50mg tablets, and should be a dose that can be administered in
equal divided doses twice daily.
The primary safety variables include reported adverse events (AEs), subject withdrawals due to 
AEs, and serious AEs (SAEs). 
2
INTRODUCTION
Epilepsy is the second most prevalent neurological disorder in the world. More than 40 million 
people suffer from epilepsy – about 1% of the world’s population (Dichek, 1999). Although 
some forms of epilepsy may respond to surgical treatment and others may not require any 
treatment at all, most patients with epilepsy require appropriate pharmacological therapy 
(Perucca, 1996). In the past decade, several new options for the medical treatment of epilepsy 
have been introduced, including novel antiepileptic drugs (AEDs) and vagus nerve stimulation.
The newer AEDs differ from older agents in several important ways, including mechanism of 
action, spectrum of activity, and pharmacokinetic (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 (Beghi and Sander, 2008). 
Therefore, a need remains for AEDs with improved effectiveness and tolerability (Shorvon, 
2009).
Lacosamide belongs to a novel class of functionalized amino acids. Lacosamide has proven to be 
an effective and 
 adjunctive treatment for partial-onset seizures, with or without secondary 
generalization, based on 3 double-blind, placebo-controlled, multicenter studies (SP667, SP754, 
and SP755) in subjects with difficult-to-control partial-onset seizures. Lacosamide has also been 
shown to be an effective and 
 adjunctive treatment over the long term (up to 9 years) for 
subjects with partial-onset seizures. Lacosamide has been approved in the EU as adjunctive 
therapy in the treatment of partial-onset seizures with or without secondary generalization in 
patients 16 years of age and older (oral tablets, syrup, and solution for intravenous [iv] infusion). 
Lacosamide has also been approved in the US as adjunctive therapy in the treatment of 
partial-onset seizures in patients 17 years of age and older (oral tablets, oral solution, and 
solution for iv infusion). In addition, LCM has been approved for a similar epilepsy indication in 
other countries. Use of a loading dose for initiation of adjunctive LCM treatment (single loading 
dose of LCM 200mg, followed approximately 12 hours later by LCM 100mg twice daily 
[200mg/day] maintenance dose regimen) is approved in the EU, US, and other countries. 
The efficacy and safety of LCM as monotherapy in partial-onset seizures were established in 
SP902, a Phase 3, historical-controlled, multicenter, double-blind, randomized, conversion to 
monotherapy study in 425 adult subjects. The results of the efficacy analyses demonstrate that 
the LCM 400mg/day dose was efficacious as withdrawal to monotherapy in subjects with 
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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 11 of 48
partial-onset seizures. Lacosamide, at doses of 400mg/day and 300mg/day, was 
 and well 
tolerated when administered as monotherapy to subjects with partial-onset seizures, with an AE 
profile similar to that reported for LCM as adjunctive therapy.
Based on these results, LCM as monotherapy in the treatment of partial-onset seizures in patients 
with epilepsy aged 17 years and older was approved on 29 Aug 2014 in the US. Use of a LCM 
200mg loading dose for initiation of LCM monotherapy or conversion to LCM monotherapy is 
also approved in the US.
In the clinical development program for LCM, safety and tolerability of multiple doses of up to 
LCM 400mg given twice daily (LCM 800mg/day) were evaluated in approximately 700 unique 
healthy subjects who received LCM in Phase 1 studies. Lacosamide is rapidly and completely 
absorbed after oral administration and has minimal protein-binding properties, thus a low risk of 
displacement drug-drug interactions. Lacosamide is neither a strong inhibitor nor a known 
inducer of the CYP450 enzymes and hence has a low potential for drug-drug interactions. Food 
does not affect the rate and extent of absorption. Peak plasma concentrations occur between 0.5 
and 4 hours after dosing. The PK properties of LCM are proportional to dose, with low 
intrasubject and intersubject variability. The terminal half-life of the unchanged drug in plasma is 
approximately 13 hours allowing for a twice-daily dose regimen. The O-desmethyl metabolite 
(referred to as SPM 12809) is excreted in the urine, represents about 30% of the dose, and has no 
known pharmacological activity. After single dose administration in healthy subjects, 
bioequivalence has been shown between the tablet and solution for iv infusion as well as 
between the tablet and oral solution (syrup) formulations.
The efficacy and safety of LCM have also been evaluated in Phase 2/3 studies as adjunctive oral 
therapy in over 1300 adult subjects with partial-onset seizures and as oral monotherapy in over 
2400 adult subjects in other indications (eg, neuropathic pain, osteoarthritis). The development 
programs for osteoarthritis and diabetic neuropathic pain were discontinued and LCM is not 
approved for these indications. Further information on LCM preclinical results, as well as the 
PK, efficacy, and safety profiles, can be obtained from the current version of the LCM 
Investigator’s Brochure.
SP0993 was designed to compare the efficacy and safety of LCM to CBZ-CR when used as 
monotherapy in subjects ≥16 years of age newly or recently diagnosed with epilepsy and 
experiencing partial-onset seizures or generalized tonic-clonic seizures and employed a
noninferiority design in accordance with EMA guidelines (CHMP/EWP/566/98, 2010). Subjects 
were randomized to receive either CBZ-CR (400mg/day to 1200mg/day) or LCM (200mg/day to 
600mg/day). The dose ranges for CBZ-CR and LCM used in SP0994 are anticipated to be 
clinically 
 and effective for monotherapy treatment (Gilliam et al, 1998; Faught et al, 1993; 
Sachdeo et al, 1992). 
SP0994 was designed as a follow-up study for SP0993 allowing collection of long-term safety 
and tolerability data in a controlled and blinded manner and also allowed subjects who 
completed SP0993 to continue with the same treatment regime they had been randomized to in 
SP0993 while also maintaining the study blind for SP0993 until SP0993 database lock.
Following the database lock and unblinding of SP0993, SP0994 will be unblinded. The 
individual subject treatment (ie, LCM or CBZ-CR) will be made known to both the subject and 
the investigator. Once the program for follow-up access to LCM monotherapy is established and 
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 12 of 48
the SP0993 database is locked, a Termination Visit will be scheduled as soon as possible. For 
subjects who were receiving LCM in SP0994, continued access to open-label follow-up
treatment with LCM will be provided by UCB within SP1042 for use as monotherapy until 
marketing application for LCM is approved and LCM is commercially available for 
monotherapy in the subject’s country, or UCB has determined that the clinical development 
program for the monotherapy indication will be formally discontinued, or up to a maximum 
period of 3 years, whichever is earlier. Subjects who were receiving CBZ-CR in SP0994, and 
who wish to continue treatment after the close of SP0994, may be prescribed CBZ by their 
physician (ie, not supplied by UCB) if medically appropriate and will not be required to taper 
CBZ. Subjects receiving CBZ-CR will not be allowed to participate in SP1042. Subjects who do 
not continue treatment with LCM or CBZ-CR should be tapered off study medication.
The present study, SP1042, is an open-label follow-up study designed to allow the collection of 
long-term safety data of LCM (200mg/day to 600mg/day) used as monotherapy in subjects who 
were treated with LCM and completed SP0994 and will allow such subjects to continue with the 
same treatment until marketing application for LCM is approved and LCM is commercially 
available for monotherapy in the subject’s country, or UCB has determined that the clinical 
development program for the monotherapy indication will be formally discontinued, or up to a 
maximum period of 3 years, whichever is earlier.
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) Guidelines for Good Clinical Practice (GCP), and the applicable regulatory 
requirements.
3
STUDY OBJECTIVE
The primary objective of the study is to assess the long-term safety and tolerability of LCM 
dosed at 200mg/day to 600mg/day when used as monotherapy in subjects, with partial-onset
seizures or generalized tonic-clonic seizures (without clear focal origin), who completed SP0994 
and received LCM.
4
STUDY VARIABLES
4.1
Safety variables
4.1.1
Primary safety variables
The primary safety variables are as follows:
x
AEs reported spontaneously by the subject and/or caregiver or observed by the investigator
x
Withdrawals due to AEs
x
SAEs
5
STUDY DESIGN
5.1
Study description
SP1042 is a long-term, open-label, follow-up study for subjects being treated with LCM 
monotherapy at the time of unblinding of SP0994. Following the database lock and unblinding of 
SP0993, SP0994 will be unblinded. Once the program for follow-up access to LCM 
monotherapy is established and the SP0993 database is locked, a Termination Visit will be 
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 13 of 48
scheduled as soon as possible for subjects in SP0994. Subjects in SP0994 who were receiving 
LCM will have the opportunity to participate in SP1042 and will have access to open-label 
follow-up treatment with LCM. Subjects who were receiving CBZ-CR or who were in LCM
taper in SP0994 at the time of unblinding will not be allowed to participate in SP1042. Subjects 
who do not wish to continue LCM therapy after unblinding of SP0994 will be tapered off LCM 
and will not participate in SP1042.
Visit 1 for SP1042 will be the same as the Termination Visit of SP0994. Prior to or at Visit 1 of
SP1042, the subject’s informed consent will be signed and eligibility assessed, concomitant 
medications including AEDs will be recorded, AEs will be assessed, and LCM dispensed (call to 
interactive voice/web response system [IXRS]). The subject will subsequently enter the 
Treatment Phase of SP1042. Clinic visits are scheduled approximately every 26 weeks relative to 
the SP1042 Visit 1 date. Dose modifications required for optimization of seizure control or 
tolerability issues will be addressed in Unscheduled Visits or regularly scheduled visits. A visit 
window of ±7 days relative to Visit 1 is applicable for all regularly scheduled visits.
In SP0994, subjects will be receiving a dose of LCM 200mg/day, 300mg/day, 400mg/day, 
500mg/day, or 600mg/day and will continue to receive the same dose in SP1042 until further 
dose adjustments are required.
During SP1042 visits, investigators will be allowed to increase or decrease the dose of LCM to 
optimize tolerability and seizure control for each subject. The investigator may maintain the 
subject’s LCM dose, decrease the dose in decrements of 100mg/day per week to a minimum 
dose of LCM 200mg/day, or increase the dose in increments of 100mg/day per week up to a 
maximum dose of LCM 600mg/day. Lacosamide doses administered in this study must be from 
200mg/day to 600mg/day, must comply with doses that can be administered with LCM 50mg 
tablets, and should be a dose that can be administered in equal divided doses twice daily. The 
IXRS should be called any time there is a dose increase or dose reduction.
In order to continue study participation, subjects must maintain treatment with LCM 
monotherapy.
Subjects requiring dose escalation 
If the subject experiences a seizure at the existing dose levels, and in the opinion of the 
investigator, dose increase is the best option for the subject, the subject should attend a clinic 
visit for dose escalation. This dose escalation will be managed via an Unscheduled Visit, or a 
regularly scheduled clinic visit. The investigator can increase the LCM dose with weekly 
titration of the dose (as described above) for adequate seizure control up to a maximum dose of 
LCM 600mg/day.
If this is still not sufficient to control seizures, then the subject must be withdrawn from the study 
and either:
-
Switched from LCM to other AED per investigator's choice (In this case LCM needs to be 
tapered) or
-
Other AEDs must be added to LCM as adjunctive therapy. In this case no LCM taper is 
necessary, but the LCM dose should be adapted per investigator's judgment.
In case the subject has experienced tolerability issues previously at a higher dose in 
SP0993/SP0994, then it will be at the investigator’s discretion to allow the subject to continue in 
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 14 of 48
the study with appropriate dose escalation for adequate seizure control or to withdraw the subject 
from the study after appropriate tapering of LCM therapy. 
Subjects requiring dose reduction
If, in the opinion of the investigator, the subject’s AEs indicate that the dose is at an intolerable 
level, the subject’s dose can be decreased (in decrements of not more than 100mg/day per week) 
to a minimum of LCM 200mg/day, provided an optimum seizure control can be achieved at the 
reduced dose. It will be at the investigator’s discretion to withdraw the subject from the study in 
case a dose reduction for tolerability issues cannot be achieved without compromising optimum 
seizure control. This dose reduction will be managed via an Unscheduled Visit, phone call, or a 
regularly scheduled clinic visit. Subjects who enter SP1042 on the lowest dose level 
(LCM 200mg/day) and who develop intolerance should be withdrawn from the study.
If, in the investigator’s opinion, a lower dose of LCM is medically more suitable for a subject, 
the decision to allow such patients to continue study on a lower dose of LCM will be made based 
on appropriate medical justification and after prior discussion with the study Medical Monitor.
The overall dosing schedule during the Treatment Phase is summarized in Table 7‒1.
Early Termination Visit with tapering of LCM
Subjects who discontinue prematurely from SP1042 and who will not continue further treatment 
with LCM should gradually taper LCM following an Early Termination Visit. These subjects 
will perform an Early Termination Visit followed by the visits required for End-of-Study Phase.
Subjects should be tapered off LCM at recommended decreasing steps of 200mg/day/week. A 
slower taper (eg, 100mg/day/week) or faster taper is permitted, if medically necessary; however,
the maximum duration of tapering should not exceed 6 weeks. Subjects will attend a Final Visit 
2 weeks after the final dose of LCM. In the case of LCM withdrawal and taper, the investigator 
is allowed to add any other AED during the End-of-Study Phase, following the investigator’s 
medical judgment. 
Early Termination Visit without tapering of LCM
Subjects who discontinue from the study as a result of requiring treatment with other AEDs will 
return for an Early Termination Visit, and may be prescribed LCM by their physician (ie, not 
supplied by UCB) as adjunctive therapy if LCM is well tolerated by the subject (dose should be 
adapted as per investigator’s judgment). The Early Termination Visit will be the last study visit 
for these subjects.
Termination Visit 
A termination visit will be performed for subjects who are ongoing in the Treatment Phase at the 
time that the marketing application is approved and LCM is commercially available for 
monotherapy in the subject’s country, or UCB has determined that the clinical development 
program for the monotherapy indication will be formally discontinued, or up to a maximum 
period of 3 years, whichever is earlier. Subjects may be immediately prescribed commercially 
available LCM. In this instance, the Termination Visit will be the last study visit completed by 
the subject. If subjects do not continue with LCM treatment, following the Termination Visit, 
subjects will be tapered off LCM. The Final Visit will be conducted 2 weeks after the final dose 
of LCM.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 15 of 48
Dosing schedules during the End-of-Study Phase are described in Table 7‒1.
5.1.1
Study duration per subject
Subjects will be allowed to continue treatment in this study until marketing application is 
approved and LCM is commercially available for monotherapy in the subject’s country, or UCB 
has determined that the clinical development program for the monotherapy indication will be 
formally discontinued, or up to a maximum period of 3 years, whichever is earlier. The 
maximum total duration of the study will be 164 weeks, including up to a 156-week Treatment 
Phase duration and up to an 8-week End-of-Study Phase.
The end of the study is defined as the date of the last visit of the last subject in the study.
5.1.2
Planned number of subjects and sites
Approximately 150 subjects will participate at approximately 70 sites. 
5.1.3
Anticipated regions and countries
The countries planned for participation in this study are Bulgaria, Finland, France, Germany, 
Japan, Latvia, Mexico, Philippines, Poland, Republic of Korea, Russia, Sweden, Switzerland, 
and Ukraine.
5.2
Schedule of study assessments
Table 5‒1 presents the tabular scheme of study assessments.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 16 of 48
Table 5‒1:
Schedule of study assessments
Assessments
Treatment Phasea
Early Termination 
/Termination Visitb
End-of-Study 
Phasec
Unscheduled 
Visitd
Visit
V1e
V2, V3, V4,
V5, V6
Final Visit
Week
W0
W26, W52, W78, 
W104, W130
NA
NA
NA
Written informed consent
X
Demographic data
X
Verification of inclusion/exclusion 
criteria
X
Concomitant AEDsf
X
X
X
X
X
Concomitant medications
X
X
X
X
X
Concomitant medical procedures
X
X
X
X
X
Laboratory tests:
Chemistry
Xg
X
X
X
Hematology
Xg
X
X
X
Urinalysis
Xg
X
X
X
Pregnancy Testh
Xg
X
X
X
Call IXRSi
X
X
X
X
Dispense IMP
X
X
Xj
Review/return IMP
X
X
X
Withdrawal criteria
X
X
X
X
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 17 of 48
Table 5‒1:
Schedule of study assessments
Assessments
Treatment Phasea
Early Termination 
/Termination Visitb
End-of-Study 
Phasec
Unscheduled 
Visitd
Visit
V1e
V2, V3, V4,
V5, V6
Final Visit
Week
W0
W26, W52, W78, 
W104, W130
NA
NA
NA
Recording of adverse eventsk
X
X
X
X
X
AED=antiepileptic drug; ECG=electrocardiogram; IMP=investigational medicinal product; IXRS=Interactive Voice Response System; LCM=lacosamide; 
NA=not applicable; V=Visit; W=week;
a A visit window of  ±7 days relative to the Visit 1 is applicable for all regularly scheduled visits. A clinic visit will occur approximately every 26 weeks relative 
to the SP1042 Visit 1.
b The Termination Visit will be performed at Week 156 or earlier, ie, in countries where marketing application is approved and LCM is commercially available 
for monotherapy prior to Week 156, or UCB has determined that the clinical development program for the monotherapy indication will be formally 
discontinued prior to Week 156. An Early Termination Visit must be completed for all subjects who prematurely discontinue from the study, followed by a 
Final Visit (End-of-Study Phase). The Final Visit will occur 2 weeks after the final dose of LCM.
c The End-of-Study Phase starts after the Early Termination Visit or Termination Visit. In case of LCM withdrawal and taper, the investigator is allowed to add 
any other AED during the End-of-Study Phase, following the investigator’s medical judgment. A Final Visit will be completed 2 weeks after the final dose of 
LCM.
d An Unscheduled Visit may be performed at the discretion of the investigator. Such visits may be necessary if the dosage of LCM is to be adjusted. If an 
Unscheduled Visit is needed, then the assessments noted will be performed. Additional assessments may be performed at the investigator’s discretion.
e Visit 1 for SP1042 will be the same as the Termination Visit of SP0994. Prior to or at Visit 1 of SP1042, the subject’s informed consent will be signed and 
eligibility assessed, concomitant medications including AEDs will be recorded, AEs will be assessed, and LCM dispensed (call to IXRS).
f If circumstances obligate the investigator to add an additional AED treatment as a function of safety (eg, seizure control), the subject must be withdrawn from 
the study but the additional AED may be added prior to the subject’s termination from the study if this treatment approach is in the best safety interest of the 
subject. The use of benzodiazepines as rescue for epilepsy is allowed if taken at a maximum frequency of once per week. The use of benzodiazepines for 
indications other than epilepsy rescue therapy is permitted.
g The designated procedures will serve as the point of data for both the Termination Visit of SP0994 and Visit 1 of SP1042.
h Urine pregnancy tests may be performed for all designated study visits.
i The IXRS should be called for any cases of dose adjustment.
j Dispensing of LCM will be done at the Termination Visit/Early Termination Visit only if tapering of LCM is required.
k If the subject reports an AE which could be due to a cardiac condition, an electrocardiogram (ECG) should be performed. Signs and symptoms of depression 
and/or suicidal ideation or suicidal behavior should be monitored as a part of the AE assessment.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 18 of 48
5.3
Rationale for study design and selection of dose
SP1042 is an open-label follow-up study designed to allow the collection of long-term safety and 
tolerability data of LCM (200mg/day to 600mg/day) used as monotherapy in subjects, having 
partial-onset or generalized tonic-clonic seizures, treated with LCM as monotherapy and who
completed SP0994. The study will allow subjects treated with LCM in SP0994 to continue 
treatment in SP1042 until marketing application is approved and LCM is commercially available 
for monotherapy in the subject’s country, or UCB has determined that the clinical development 
program for the monotherapy indication will be formally discontinued, or for a maximum of 
3 years duration, whichever is earlier.
Subjects will be receiving LCM in a dose range of 200mg/day to 600mg/day and this dose range 
is anticipated to be clinically 
 and effective for monotherapy treatment.
Subjects will be monitored for seizure control and occurrence of AEs throughout the study.
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 Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject or by the parent(s) or legal 
representative. The Informed Consent form or a specific Assent form, where required, will be 
signed and dated by minors.
2. Subject/legal representative is considered reliable and capable of adhering to the protocol,
visit schedule, and medication intake according to the judgment of the investigator.
3. Subject has completed the Termination Visit of SP0994 and has been treated with LCM 
monotherapy.
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria are met:
1. Subject is receiving any investigational drugs or using any experimental devices in addition 
to LCM.
2. Subject experienced a seizure at the third target dose (ie, LCM 600 mg/day) during SP0994.
3. Subject requires another AED for the treatment of seizures.
4. Subject meets a “must” withdrawal criterion for the previous study, SP0994.
5. Subject is experiencing an ongoing SAE from the previous study, SP0994.
6. Female subject who is pregnant or nursing, and/or a woman of childbearing potential who is 
not surgically sterile, 2 year postmenopausal or does not practice one highly effective method 
of contraception (according to 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.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 19 of 48
6.3
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care.
Subjects must be withdrawn from the study if any of the following events occur:
1. Subject experiences emergence of a seizure type other than partial-onset seizures or
generalized tonic-clonic seizures (without clear focal origin), or occurrence of status 
epilepticus, or for any other safety reason. 
2. Subject develops second or third degree atrioventricular (AV) block or if the investigator 
feels it is in the best interest of the subject to withdraw from the study. 
3. Subject experiences a seizure in SP1042 at the highest allowed LCM dose (600mg/day) and 
requires either an increase in dose or the addition of or change to another AED.
4. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test. Female subjects who plan to become pregnant should inform the investigator and should 
also be withdrawn from the study.
5. Subject requires another AED for any reason. If circumstances obligate the investigator to 
add an additional AED treatment as a function of safety (eg, seizure control), the subject 
must be withdrawn from the study but the additional AED may be added prior to the 
subject’s termination from the study if this treatment approach is in the best safety interest of 
the subject.
6. Request of the sponsor or regulatory agency.
7. Subject is unwilling or unable to continue and withdraws his/her consent.
8. In the case of liver function test (LFT) results of transaminases (aspartate aminotransferase 
[AST] and/or alanine aminotransferase [ALT]) ≥3x upper limit of normal (ULN) to <5xULN 
and total bilirubin ≥2xULN or transaminases (AST and/or ALT) ≥5xULN, LCM must be 
immediately discontinued and the subject withdrawn from the study. The LFTs will be 
repeated as soon as possible, and in no case more than 1 week later. In all cases of 
transaminases (AST, ALT, or both) ≥3xULN, testing for hepatitis A, B, and C will be done. 
Referral to a specialist (ie, hepatologist or gastroenterologist) is at the discretion of the 
investigator. This is recommended especially if the transaminase abnormalities >3xULN 
persist after discontinuation of the study medication.
9. Subject experiences AEs related to suicide attempt or severe suicidal ideation.
Subjects may be withdrawn from the study if any of the following events occur:
1. Subject requires a medication that is not permitted. Benzodiazepines as rescue therapy for 
epilepsy may be used as needed but not more frequently than once per week. The use of 
benzodiazepines for a nonepilepsy indication is permitted.
2. Subject is noncompliant with the study procedures or medications, in the opinion of the 
investigator.
3. Transaminases (AST, ALT, or both) ≥3xULN to <5xULN, in the presence of normal total 
bilirubin, will be repeated within a few days. If the repeat testing confirms the abnormality 
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 20 of 48
(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.
4. Subject develops an illness that would interfere with his/her continued participation.
5. Subject requires a LCM dose level below 200mg/day. In the investigator’s opinion, if a lower
dose of LCM is medically appropriate for a subject, a decision to continue such subjects in 
the study will be made after prior consultation with the Medical Monitor and with 
appropriate medical justification. 
Subjects meeting “must” Withdrawal Criteria must return for the Early Termination Visit and 
complete all Early Termination assessments. Subjects who require taper will enter the 
End-of-Study Phase and should complete a Final Visit 2 weeks after the final dose of IMP.
Investigators should attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow up, the investigator should make an 
effort (at least 1 phone call and 1 written message to the subject), and document his/her effort 
(date and summary of the phone call and copy of the written message in the source documents), 
to complete the final evaluation. All results of these evaluations and observations, together with a 
narrative description of the reason(s) for removing the subject, must be recorded in the source 
documents. The 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.
7
STUDY TREATMENT
7.1
Description of investigational medicinal product
Investigational medicinal product (IMP) is LCM oral tablets. This product will be supplied by 
the UCB Clinical Supply Unit. Drug supplies will consist of commercially available LCM 
formulation (VIMPAT® - pinkish, oval film-coated tablets debossed with “SP” on one side and 
“50” on the other side) and will be distributed in study-specific labeled packages at a strength of 
50mg.
7.2
Treatment to be administered
Lacosamide will be administered orally twice daily (at approximately 12 hour intervals in the 
morning and in the evening) in 2 divided doses (see Table 7‒1). Medication must not be chewed 
and must be swallowed with a sufficient amount of fluid. 
The dosing schedules during the Treatment Phase and End-of-Study Phase are presented in 
Table 7‒1. Subjects stopping LCM should be tapered off LCM at recommended decreasing steps 
of 200mg/day/week. A slower taper (eg, 100mg/day/week) or faster taper is permitted, if 
medically necessary; however, the maximum duration of tapering should not exceed 6 weeks.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 21 of 48
Table 7‒1:
LCM dosing schedule for Treatment Phase and End-of-Study Phase (if tapering is required)
Treatment Phase
End-of-Study Phase
Daily dose
First week
Second week
Third week
Fourth week
Fifth week
AM 
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AM dose
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AM 
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PM 
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AM 
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AM 
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PM 
dose
(mg)
AM 
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PM 
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LCM 200mg/day (100mg bid)
100
100
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2
2
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LCM 300mg/day (150mg bid)
150
150
50
50
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Subject has exited study
Number of LCM tablets
3
3
1
1
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LCM 400mg/day (200mg bid)
200
200
100
100
-
-
-
-
Subject has exited study
Number of LCM tablets
4
4
2
2
-
-
-
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LCM 500mg/day (250mg bid)
250
250
150
150
50
50
-
-
-
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Subject has 
exited study
Number of LCM tablets
5
5
3
3
1
1
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-
-
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LCM 600mg/day (300mg bid)
300
300
200
200
100
100
-
-
-
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Subject has 
exited study
Number of LCM tablets
6
6
4
4
2
2
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 22 of 48
7.3
Packaging
Lacosamide tablets are manufactured, packaged, and labeled according to Good Manufacturing 
Practice (GMP) guidelines and applicable laws or regulations. The IMP is suitably packaged in 
such a way as to protect the IMP from deterioration during transport and storage.
The IMP will be packaged in clinical high-density polyethylene bottles with study-specific 
labels. The sites' supplies will be controlled by the IXRS. All the bottles will be uniquely 
numbered.
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current ICH guidelines on 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. 
Investigational medicinal product stored by the investigator is to be kept in a secured area with 
limited access.
Appropriate storage conditions must be ensured either by controlled room temperature or by 
completion of a temperature log in accordance with local requirements on a regular basis (daily 
to weekly), showing minimum and maximum temperatures reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately communicated to the
Clinical Project Manager (CPM) (or designee) before further use of the IMP.
The CPM (or designee) will transmit the out-of-range temperature (copy of the temperature log 
and duration of the out-of-range temperature, if available) to the Clinical Supply Associate or 
designee. Based on discussion with a UCB Quality Assurance representative, the Clinical Supply 
Associate or designee will then provide the CPM (or designee) with instructions for the site 
regarding use of the IMP.
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 or designee must also be recorded on the appropriate forms. All supplies and 
pharmacy documentation must be made available throughout the study for UCB (or designee) to 
review.
The investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed.
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.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 23 of 48
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 (or designee), 
preferably in their original package. Investigational medicinal product intended for the study 
cannot be used for any other purpose than that described in this protocol.
7.7
Procedures for monitoring subject compliance
At each visit after IMP is dispensed, subjects must return all unused IMP 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.
7.8
Concomitant medications/treatments
7.8.1
Permitted concomitant treatments (medications and therapies)
The following concomitant medications are permitted during the study:
x
The use of benzodiazepines as rescue therapy for epilepsy is allowed if taken at a maximum 
frequency of once per week during study participation; more frequent use precludes subjects 
from study participation.
x
Benzodiazepines used for nonepileptic conditions will be allowed in the study.
All medications, that are not included in the section of prohibited medication below, will be 
allowed for use as a concomitant treatment in case of necessity.
7.8.2
Prohibited concomitant treatments (medications and therapies)
Addition or use of any concomitant AED during the study period is forbidden except if 
circumstances oblige the investigator to do so as a function of safety. Any additions of 
concomitant AEDs during the study period constitute a protocol deviation. If this occurs, the 
investigator will contact the Medical Monitor immediately. In the case of study withdrawal and 
LCM taper, the investigator is allowed to add any other AED, following the investigator’s 
medical judgment.
7.8.3
Permitted agents to be used with caution
Lacosamide should be used with caution in patients treated with medicinal products known to be 
associated with PR prolongation and in patients treated with Class I antiarrhythmics 
(eg, quinidine, procainamide, disopyramide, lidocaine, propafenone).
7.9
Blinding
Not applicable.
7.10
Randomization and numbering of subjects
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 24 of 48
8
STUDY PROCEDURES BY VISIT 
A visit window of ±7 days relative to Visit 1 is applicable for all regularly scheduled visits. A 
clinic visit will occur approximately every 26 weeks relative to the SP1042 Visit 1 date. 
A detailed tabular schedule of study procedures is provided in Section 5.2.
8.1
Visit 1 (Week 0)
Visit 1 of SP1042 will correspond to the last visit of SP0994 which is the Termination Visit.
Prior to or at Visit 1 in SP1042, 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). Before 
conduct of any study-related procedures, the subject is required to sign and date the IRB/IEC 
approved informed consent if he/she decides to participate in the study.
Prior to or at Visit 1, the subject’s eligibility will be assessed based on the inclusion/exclusion 
criteria, concomitant medications including AEDs will be recorded, AEs will be assessed, and 
LCM dispensed (call to IXRS).
The following assessments and procedures will be performed for eligible subjects during Visit 1
of SP1042:
x
Written Informed Consent
x
Verification of inclusion/exclusion criteria
x
Demographic data
x
Concomitant AEDs
x
Concomitant medications
x
Concomitant medical procedures
x
Call IXRS (for any dose adjustments)
x
Dispense IMP
The following procedures will correspond to both the Termination Visit of SP0994 and Visit 1 of
SP1042:
x
Blood sample for clinical chemistry and hematology 
x
Urine sample for urinalysis
x
Urine pregnancy test
x
Recording of AEs
8.2
Visit 2, 3, 4, 5, 6 (Week 26, 52, 78, 104, 130)-Treatment Visits
The following assessments and procedures will be performed at the visits:
x
Concomitant AEDs
x
Concomitant medications
x
Concomitant medical procedures
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 25 of 48
x
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8.3
Early Termination Visit/Termination Visit
The following assessments and procedures will be performed at the visit:
x
Concomitant AEDs
x
Concomitant medications
x
Concomitant medical procedures
x
Blood sample for clinical chemistry and hematology 
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x
Urine pregnancy test
x
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x
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x
Review/return IMP
8.4
Final Visit
The following assessments and procedures will be performed at the visit:
x
Concomitant AEDs
x
Concomitant medications
x
Concomitant medical procedures
x
Blood sample for clinical chemistry and hematology
x
Urine sample for urinalysis
x
Urine pregnancy test
x
Recording of AEs
x
Call IXRS 
x
Review/return IMP
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 26 of 48
8.5
Unscheduled Visit
An Unscheduled Visit may be performed at any time after Visit 1, at the discretion of the 
investigator. In addition to the required assessments listed below, further assessments can be 
completed as needed. The IXRS should be called if IMP has to be dispensed at this visit.
x
Concomitant AEDs
x
Concomitant medications
x
Concomitant medical procedures
x
Withdrawal criteria
x
Recording of AEs
9
ASSESSMENT OF SAFETY
9.1
Adverse events
9.1.1
Definition of adverse event
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol, must be reported in the CRF even if no IMP was taken but specific 
study procedures were conducted. This includes all AEs not present prior to the initial visit and 
all AEs that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
investigator from the subject’s history or the Baseline Period.
9.1.2
Procedures for reporting and recording adverse events
The subject will be given the opportunity to report AEs spontaneously. A general prompt will 
also be given at each study visit to detect AEs. For example:
“Did you notice anything unusual about your health (since your last visit)?”
9.1.3
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.
Details for completion of the Adverse Event CRF (including judgment of relationship to IMP)
are described in the CRF Completion Guidelines.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 27 of 48
9.1.4
Follow up of adverse events
An AE should be followed until it has resolved, has a stable sequelae, the investigator determines 
that it is no longer clinically significant, or the subject is lost to follow up. 
If an AE is ongoing at the end of the study for a subject, follow up should be provided until 
resolution/stable level of sequelae is achieved, or until the investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow up. If no follow up is provided, the 
investigator must provide a justification. The follow up will usually be continued for 30 days 
after the subject has discontinued his/her IMP.
9.1.5
Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:
x
The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening”
x
The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one
9.1.6
Pregnancy
If an investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the investigator must immediately notify UCB’s Drug Safety (DS) department by providing the 
completed Pregnancy Report and Outcome form (for contact details see SAE reporting 
information at the beginning of this protocol). The subject should be withdrawn from the study 
as soon as pregnancy is known (by positive pregnancy test), and the following should be 
completed:
x
The subject should return for an Early Termination Visit.
x
The subject should immediately stop the intake of the IMP or undergo tapering as instructed 
at the Early Termination Visit.
x
A Final Visit should be scheduled 2 weeks after the subject has discontinued the IMP.
The investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
The pregnancy will be documented on the Pregnancy Report and Outcome form provided to the 
investigator. The progression of the pregnancy and the eventual birth (if applicable) must be 
followed up using the Pregnancy Report and Outcome form in which the investigator has to 
report on the health of the mother and of the child. Every reasonable attempt should be made to 
follow the health of the child for 30 days after birth for any significant medical issues. In certain 
circumstances, UCB may request that follow up is continued for a period longer than 30 days. If
the subject is lost to follow up and/or refuses to give information, written documentation of 
attempts to contact the subject needs to be provided by the investigator and filed at the site. 
UCB’s DS department is the primary contact for any questions related to the data collection for 
the pregnancy, eventual birth, and follow up.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent form that has been approved by the responsible IRB/IEC and should 
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 28 of 48
be available in the investigator site file. In case of questions about the consent process, the
investigator may contact the UCB/contract research organization (CRO) contract monitor for the
study. The investigator will complete the Pregnancy Report and Outcome form and send it to 
UCB’s DS department (for contact details see SAE reporting information at the beginning of this 
protocol) only after the partner has agreed that additional information can be captured and has 
provided the signed Partner Pregnancy Consent form. UCB’s DS department is also the primary 
contact for any questions related to the data collection for the partner pregnancy, eventual birth,
and follow up.
A pregnancy becomes a SAE in the following circumstances: miscarriage, abortion (elective or 
spontaneous), unintended pregnancy after hormonal contraceptive failure (if the hormonal 
contraceptive was correctly used), ectopic pregnancy, fetal demise, or any congenital 
anomaly/birth defect of the baby. Those SAEs must be additionally reported using the 
Investigator SAE Report form.
9.1.7
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).
9.1.8
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 Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the DS 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 electrocardiogram [ECG] results) for which data will be periodically 
reviewed during the course of the study.
9.2
Serious adverse events
9.2.1
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:
x
Death
x
Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)
x
Significant or persistent disability/incapacity
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 29 of 48
x
Congenital anomaly/birth defect (including that occurring in a fetus)
x
Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious
(Important medical events may include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse.)
x
Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening 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.)
9.2.2
Procedures for reporting serious adverse events
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by 
the site (see contact information for SAE reporting listed in the Serious Adverse Event Reporting 
section at the front of the protocol). The investigator must forward to UCB (or its representative) 
a duly completed “Investigator SAE Report Form for Development Drug” (SAE report form) 
provided by UCB, even if the data are incomplete, or if it is obvious that more data will be 
needed in order to draw any conclusions. Information recorded on this form will be entered into 
the global safety database.
An Investigator SAE report form will be provided to the investigator. The Investigator SAE 
Report form must be completed in English. 
It is important for the investigator, when completing the SAE report form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the investigator is very important for UCB to consider in assessing the safety of the IMP 
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner.
Additional information (eg, autopsy or laboratory reports) received by the investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 30 of 48
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE report form.
The investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the investigator is certain that they are in no way associated with the IMP), up to 
30 days from the end of the study for each subject, and to also inform participating subjects of 
the need to inform the investigator of any SAE within this period. Serious AEs that the
investigator thinks may be associated with the IMP must be reported to UCB regardless of the 
time between the event and the end of the study.
Upon receipt of the SAE report form, UCB will perform an assessment of expectedness of the 
reported SAE. The assessment of the expectedness of the SAE is based on the current version of 
Investigator’s Brochure for LCM.
9.2.3
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 DS
database without limitation of time.
9.3
Adverse events of special interest
An AE of special interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.
The following are AEs of special interest:
x
The following arrhythmias: atrial fibrillation/flutter, ventricular tachycardia or fibrillation, 
AV block (2nd degree Type I and II and 3rd degree), and marked bradycardia (<45 beats/min)
x
Syncope or loss of consciousness (other than seizure related)
x
Serious suspected multiorgan hypersensitivity reactions
Serious suspected multiorgan hypersensitivity cases may be identified and reported to the 
sponsor by the investigator using the following algorithm as agreed with the United States 
Food and Drug Administration:
An AE or laboratory value (as defined below) suggestive of internal organ involvement 
(including but not limited to hepatitis, nephritis, pneumonitis, carditis, colitis, encephalitis, 
pancreatitis, myositis, arthritis, or hematologic system involvement) combined with at least 1
of the following: fever, rash, lymphadenopathy, or eosinophilia.
Treatment-emergent abnormal laboratory value criteria suggestive of internal organ 
involvement or eosinophilia:

Eosinophils % ≥10%

Eosinophils absolute ≥0.5G/L

Neutrophils absolute <1.5G/L
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Platelets ≤100G/L
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 31 of 48

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9.4
Immediate reporting of adverse events
The following AEs must be reported immediately:
x
SAE: AE that the investigator classifies as serious by the above definitions regardless of 
causality
x
Suspected transmission of an infectious agent via a medicinal product
x
AE of special interest (see Section 9.3)
9.5
Anticipated serious adverse events
The following list of Anticipated SAEs has been identified, as these events are anticipated to 
occur in the population studied in this protocol at some frequency that is independent of drug 
exposure. This original list will remain in effect for the duration of the protocol.
This list does not change the investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 9.2.2. The following list of anticipated SAEs has been identified as 
these events are anticipated to occur in the epilepsy population at some frequency that is 
independent of drug exposure.
Table 9‒1:
Anticipated SAEs for the adult epileptic population
MedDRA SOC
MedDRA PT
Congenital, familial and genetic disorders
Teratogenicity
General disorders and administrative site conditions
Sudden unexplained death in epilepsy
Nervous system disorders
Convulsiona
Incontinence
Status epilepticus
Pregancy, puerperium and perinatal disorders
Abortion spontaneous
Psychiatric disorders
Psychotic behaviour
Abnormal behaviour
Anxiety
Sleep disorder
Reproductive system and breast disorders
Menstrual disorder
Impotence
MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; SAE=serious adverse event; 
SOC=system organ class
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 32 of 48
9.6
Laboratory measurements
Blood and urine specimens for routine assay of hematology, clinical chemistry, and urinalysis 
testing as well as pregnancy testing will be performed according to the tabular schedule of study 
procedures in Section 5.2 to monitor the safety of subjects. The specimens will be analyzed by 
the local laboratory affiliated to the site. At a minimum, the laboratory parameters specified 
below in Table 9‒2 will be tested. The individual laboratory parameter result data will not be 
collected; however, the investigator will report out of range results judged to be clinically 
significant as an AE, as noted in Section 9.1.1.
The following laboratory parameters will be measured:
Table 9‒2:
Laboratory measurements
Hematology
Chemistry
Urinalysis
Hematocrit
Calcium
pH
Hemoglobin
Phosphorus
Ketones
Platelet count
Serum electrolytes (sodium, 
potassium, chloride, 
bicarbonate)
Glucose
RBC count
Creatinine
Albumin
WBC count
BUN 
Specific gravity
Differential count
AST
Microscopic exam for blood 
cells or casts/hpf
ALT
Urine pregnancy test
Total bilirubin
Alkaline phosphatase
GGT
Glucose
Albumin
Total serum protein
Uric acid
ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; GGT=gamma 
glutamyltransferase; hpf=high power field; RBC=red blood cell; WBC=white blood cell 
9.6.1
Liver function tests
Refer to Section 6.3 for LFT withdrawal criteria.
Transaminases (AST, ALT, or both) ≥3xULN but <5xULN, in the presence of total bilirubin 
≥2xULN, or transaminases (AST, ALT, or both) ≥5xULN will result in immediate 
discontinuation of LCM and withdrawal of the subject from the study. The LFTs will be repeated 
as soon as possible, and in no case more than 1 week later.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 33 of 48
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 LCM.
In all cases of transaminases (AST, ALT, or both) ≥3xULN, testing for hepatitis A, B, and C will 
be done.
Referral to a specialist (ie, hepatologist or gastroenterologist) is at the discretion of the 
investigator. This is recommended especially if the transaminase abnormalities >3xULN persist 
after discontinuation of LCM.
9.6.2
Pregnancy testing
Females of childbearing potential (who have not been surgically sterilized or who are not at least 
2 years postmenopausal) will have urine dipstick pregnancy testing performed according to the 
tabular schedule of study procedures in Section 5.2.
10
STUDY MANAGEMENT AND ADMINISTRATION 
10.1
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 CPM of the sponsor 
within 24 hours and follow any local regulatory requirements.
10.2
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 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).
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.
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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 34 of 48
10.2.1
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 electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee).
10.2.2
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 10.2.1.
10.3
Data handling
10.3.1
Case Report form completion
In the event that the study is performed using electronic data capture (EDC), the investigator is 
responsible for prompt reporting of accurate, complete, and legible data in the electronic CRFs 
and in all required reports.
Any change or correction to the CRF after saving must be accompanied by a reason for the 
change.
Corrections made after the investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the investigator.
The investigator should maintain a list of personnel authorized to enter data into the electronic 
CRF.
Detailed instructions will be provided in the CRF Completion Guidelines.
10.3.2
Database entry and reconciliation
An EDC system will be used for the study. External electronic data will be 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 
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 35 of 48
ensure consistency of the data. In the event that the study is performed using EDC, the data are 
entered into the electronic CRFs once and are subsequently verified.
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
10.3.3
Subject Screening and Enrollment log/Subject Identification Code list
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.
10.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by the sponsor or by the investigator/institution, as specified by the 
applicable regulatory requirement(s). In addition, arrangements will be made for the return of all 
unused IMP and other material in accordance with UCB procedures for the study.
10.5
Archiving and data retention
The investigator will maintain adequate records for the study, including CRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data.
All essential documents are to be retained by the investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). The investigator will contact 
UCB for authorization prior to the destruction of any study records or in the event of accidental 
loss or destruction of any study records. The investigator will also notify UCB should he/she 
relocate or move the study-related files to a location other than that specified in the sponsor’s 
study master file.
10.6
Audit and inspection
The investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 36 of 48
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).
10.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
investigator, institution, institution staff, or designees of the sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study.
11
STATISTICS
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan.
11.1
Definition of analysis sets
The primary analysis set will be the Safety Set, which is defined as all subjects who meet the 
inclusion/exclusion criteria, sign an Informed Consent form, and take at least 1 dose of study 
medication. This analysis set will be used for summaries of all parameters.
11.2
General statistical considerations
Descriptive statistics will be used to provide an overview of the primary and other variable 
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. For continuous parameters, descriptive statistics will 
include number of subjects, mean, standard deviation, median, minimum, and maximum.
11.3
Planned safety and other analyses
11.3.1
Safety analyses
Treatment-emergent AEs (TEAEs) will be defined as those events which started on or after the 
date of first dose of IMP in SP1042, or events in which severity worsened on or after the date of 
first dose of IMP in SP1042. Adverse events which occur within 30 days after final dose of IMP 
in SP1042 will be considered treatment emergent.
Adverse events will be coded using the Medical Dictionary for Regulatory Activities®
(MedDRA), and tabulated by body system and preferred term. The incidence of TEAEs will also 
be summarized by intensity. Serious AEs and AEs which lead to premature discontinuation will 
be tabulated and listed.
All TEAEs, AEs leading to withdrawal, and SAEs will be summarized descriptively.
Available data related to laboratory tests will be presented in subject data listings.
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thereof. 


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01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 37 of 48
11.4
Handling of protocol deviations
Important protocol deviations are deviations from the protocol that could potentially have a 
meaningful impact on study conduct or on the key safety outcomes for an individual subject. The 
criteria for identifying important protocol deviations and the classification of important protocol 
deviations will be defined within the appropriate protocol-specific document (eg, the Protocol 
Deviation Specification). To the extent feasible, rules for identifying protocol deviations will be 
defined without review of the data and without consideration of the frequency of occurrence of 
such deviations.
Important protocol deviations will be reviewed as part of the ongoing data cleaning process prior 
to database lock.
11.5
Handling of dropouts or missing data
For evaluation of safety variables, subjects who prematurely discontinue the study will be 
evaluated based on the data collected at each visit attended.
11.6
Planned interim analysis and data monitoring
No interim analysis or data monitoring is planned in the study.
11.7
Determination of sample size
No formal sample size calculations have been performed for this study as there are no statistical 
hypotheses being tested. The sample size will be determined by the number of subjects in 
SP0994 who have been treated with LCM that are eligible to enter this open-label follow-up
study. It is anticipated that approximately 150 subjects who receive LCM in SP0994 will 
participate in this follow-up study.
12
ETHICS AND REGULATORY REQUIREMENTS
12.1
Informed consent
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the subject in both oral and written form by the investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the investigator.
Prior to participation in the study, the written Informed Consent form should be signed and 
personally dated by the subject, or his/her legal representative, and by the person who conducted 
the informed consent discussion (investigator or designee). The subject or his/her legal 
representative must receive a copy of the signed and dated Informed Consent form. As part of 
the consent process, each subject must consent to direct access to his/her medical records for 
study-related monitoring, auditing, 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.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 38 of 48
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.
12.2
Subject identification cards
Upon signing the Informed Consent and Assent form (as applicable), the subject or legal 
representative will be provided with a subject identification card in the language of the subject. 
The investigator will fill in the subject identifying information and medical emergency contact 
information. The investigator will instruct the subject to keep the card with him/her at all times.
12.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki.
The investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the investigator/UCB will forward copies of the protocol, Informed 
Consent form, Investigator’s Brochure, investigator’s curriculum vitae (if applicable), 
advertisement (if applicable), and all other subject-related documents to be used for the study to 
the IRB/IEC for its review and approval.
Before initiating a study, the investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol.
The investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects.
The investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the subjects. For 
minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the investigator to obtain an expedited review by the IRB/IEC as 
allowed.
As part of the IRB/IEC requirements for continuing review of approved studies, the investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of subject risk involved, but no less than 
once per year. The investigator should provide a final report to the IRB/IEC following study 
completion.
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active investigators in accordance with applicable regulatory requirements. 
The appropriate IRB/IEC will also be informed by the investigator or the sponsor, as specified by 
the applicable regulatory requirements in each concerned country. Where applicable, 
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 39 of 48
investigators are to provide the sponsor (or its representative) with evidence of such IRB/IEC 
notification.
12.4
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).
12.5
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.
13
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.
14
REFERENCES
Beghi E, Sander JW. The natural history and prognosis of epilepsy. In: Engel J Jr, Pedley TA, 
editors. Epilepsy: A Comprehensive Textbook. 2nd ed. Philadelphia: Lippincott William and 
Wilkins; 2008. p. 65-70.
CHMP/EWP/566/98 Guideline on clinical investigation of medicinal products in the treatment of 
epileptic disorders (EMA) Rev 2, 20 Jan 2010.
CPMP/ICH/135/95 Note for guidance on Good Clinical Practice (EMEA) Jul 2002.
Dichek B. Epilepsy: an ancient ailment that still eludes a cure. Scrip Magazine. 1999;76:9-11.
Faught E, Sachdeo RC, Remler MP, Chayasirisobhon S, Iragui-Madoz VJ, Ramsay RE, et al.
Felbamate monotherapy for partial-onset seizures: an active-control trial. Neurology. 
1993;43(4):688-92.
Gilliam F, Vazquez B, Sackellares JC, Chang GY, Messenheimer J, Nyberg J, et al. An 
active-control trial of lamotrigine monotherapy for partial seizures. Neurology. 1998;51(4):1018-
25.
Herman ST, Pedley TA. New options for the treatment of epilepsy. JAMA. 1998;280(8):693-4.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 40 of 48
Perucca E. Established antiepileptic drugs. Baillieres Clin Neurol. 1996;5(4):693-722.
Sachdeo R, Kramer LD, Rosenberg A, Sachdeo S. Felbamate monotherapy: controlled trial in 
patients with partial onset seizures. Ann Neurol. 1992;32(3):386-92.
Shorvon SD. Drug treatment of epilepsy in the century of the ILAE: The second 50 years, 1959-
2009. Epilepsia. 2009;50 Suppl 3:93-130.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 41 of 48
15
APPENDICES
15.1
Protocol Amendment 1
Rationale for the amendment
The purpose of this amendment is to correct a typographical error noted in the visit schedule for 
the study. As per Table 5-1: Schedule of study assessments, a total of 6 visits: V2, V3, V4, V5, 
V6, and V7 have been mentioned in the Treatment Phase at Weeks 26, 52, 78, 104, 130, and 156. 
The last visit in the Treatment Phase, ie, Visit 7/Week 156, has been deleted since this coincides 
with the Termination Visit and was mentioned in error in the Treatment Phase.
The maximum total duration of the study will be 164 weeks, including up to a 156-week 
Treatment Phase duration (with visits scheduled every 26 weeks) and up to an 8-week 
End-of-Study Phase. Last study drug dispensing in the Treatment Phase will occur at V6/Week 
130 and the subsequent visit scheduled after 26 weeks, ie, Visit 7/Week 156 will be the same as
the Termination Visit. Hence, Visit 7/Week 156, was deleted since the Termination Visit is listed 
separately.
Modifications and changes
Global changes
The following changes were made throughout the protocol:
x
Deletion of Visit 7/Week 156 throughout the protocol
Specific changes
Change #1
Table 5-1: Schedule of study assessments 
Table heading rows were updated. Footnote “b” was updated and Footnote “j” was added.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 42 of 48
Table 5-1:
Schedule of study assessments
Assessments
Treatment Phaseab
End-of-Study 
Phasec
Unscheduled 
Visitd
Visit
V1e
V2, V3,V4,     
V5,V6, V7
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/Termination Visit
Final Visit
Week
W0
W26, W52, W78, 
W104, W130, W156
NA
NA
NA
Written informed consent
X
Demographic data
X
Verification of inclusion/exclusion 
criteria
X
Concomitant AEDsf
X
X
X
X
X
Concomitant medications
X
X
X
X
X
Concomitant medical procedures
X
X
X
X
X
Laboratory tests:
Chemistry
Xg
X
X
X
Hematology
Xg
X
X
X
Urinalysis
Xg
X
X
X
Pregnancy Testh
Xg
X
X
X
Call IXRSi
X
X
X
X
Dispense IMP
X
X
X
Review/return IMP
X
X
X
Withdrawal criteria
X
X
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 43 of 48
Table 5-1:
Schedule of study assessments
Assessments
Treatment Phaseab
End-of-Study 
Phasec
Unscheduled 
Visitd
Visit
V1e
V2, V3,V4,     
V5,V6, V7
Early Termination 
/Termination Visit
Final Visit
Week
W0
W26, W52, W78, 
W104, W130, W156
NA
NA
NA
Recording of adverse eventsj
X
X
X
X
X
AED=antiepileptic drug; IMP=investigational medicinal product; IXRS=Interactive Voice Response System; NA=not applicable; V=Visit; W=week;
ECG=electrocardiogram
a A visit window of  ±7 days relative to the Visit 1 is applicable for all regularly scheduled visits. A clinic visit will occur approximately every 26 weeks relative 
to the SP1042 Visit 1.   
b Early Termination Visit must be completed for all subjects who prematurely discontinue from the study, followed by a Final Visit (End-of-Study Phase). The 
Final Visit will occur 2 weeks after the final dose of LCM.
c The End-of-Study Phase starts after the Early Termination Visit or Termination Visit. In case of LCM withdrawal and taper, the investigator is allowed to add 
any other AED during the End-of-Study Phase, following the investigator’s medical judgment. A Final Visit will be completed 2 weeks after the final dose of 
LCM.
d An Unscheduled Visit may be performed at the discretion of the investigator. Such visits may be necessary if the dosage of LCM is to be adjusted. If an 
Unscheduled Visit is needed, then the assessments noted will be performed. Additional assessments may be performed at the investigator’s discretion.
e Visit 1 for SP1042 will be the same as the Termination Visit of SP0994. Prior to or at Visit 1 of SP1042, the subject’s informed consent will be signed and 
eligibility assessed, concomitant medications including AEDs will be recorded, AEs will be assessed, and LCM dispensed (call to IXRS).
f If circumstances obligate the investigator to add an additional AED treatment as a function of safety (eg, seizure control), the subject must be withdrawn from 
the study but the additional AED may be added prior to the subject’s termination from the study if this treatment approach is in the best safety interest of the 
subject. The use of benzodiazepines as rescue for epilepsy is allowed if taken at a maximum frequency of once per week. The use of benzodiazepines for 
indications other than epilepsy rescue therapy is permitted.
g The designated procedures will serve as the point of data for both the Termination Visit of SP0994 and Visit 1 of SP1042.
h Urine pregnancy tests may be performed for all designated study visits.
i The IXRS should be called for any cases of dose adjustment.
j If the subject reports an AE which could be due to a cardiac condition, an electrocardiogram (ECG) should be performed. Signs and symptoms of depression 
and/or suicidal ideation or suicidal behavior should be monitored as a part of the AE assessment.
Has been changed to:
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 44 of 48
Table 5-1:
Schedule of study assessments
Assessments
Treatment Phasea
Early Termination 
/Termination Visitb
End-of-Study 
Phasec
Unscheduled 
Visitd
Visit
V1e
V2, V3, V4,
V5, V6
Final Visit
Week
W0
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NA
NA
NA
Written informed consent
X
Demographic data
X
Verification of inclusion/exclusion 
criteria
X
Concomitant AEDsf
X
X
X
X
X
Concomitant medications
X
X
X
X
X
Concomitant medical procedures
X
X
X
X
X
Laboratory tests:
Chemistry
Xg
X
X
X
Hematology
Xg
X
X
X
Urinalysis
Xg
X
X
X
Pregnancy Testh
Xg
X
X
X
Call IXRSi
X
X
X
X
Dispense IMP
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X
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Review/return IMP
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X
X
Withdrawal criteria
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X
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 45 of 48
Table 5-1:
Schedule of study assessments
Assessments
Treatment Phasea
Early Termination 
/Termination Visitb
End-of-Study 
Phasec
Unscheduled 
Visitd
Visit
V1e
V2, V3, V4,
V5, V6
Final Visit
Week
W0
W26, W52, W78, 
W104, W130
NA
NA
NA
Recording of adverse eventsk
X
X
X
X
X
AED=antiepileptic drug; ECG=electrocardiogram; IMP=investigational medicinal product; IXRS=Interactive Voice Response System; LCM=lacosamide; 
NA=not applicable; V=Visit; W=week;
a A visit window of  ±7 days relative to the Visit 1 is applicable for all regularly scheduled visits. A clinic visit will occur approximately every 26 weeks relative 
to the SP1042 Visit 1.   
b The Termination Visit will be performed at Week 156 or earlier, ie, in countries where marketing application is approved and LCM is commercially available 
for monotherapy prior to Week 156, or UCB has determined that the clinical development program for the monotherapy indication will be formally 
discontinued prior to Week 156. An Early Termination Visit must be completed for all subjects who prematurely discontinue from the study, followed by a 
Final Visit (End-of-Study Phase). The Final Visit will occur 2 weeks after the final dose of LCM.
c The End-of-Study Phase starts after the Early Termination Visit or Termination Visit. In case of LCM withdrawal and taper, the investigator is allowed to add 
any other AED during the End-of-Study Phase, following the investigator’s medical judgment. A Final Visit will be completed 2 weeks after the final dose of 
LCM.
d An Unscheduled Visit may be performed at the discretion of the investigator. Such visits may be necessary if the dosage of LCM is to be adjusted. If an 
Unscheduled Visit is needed, then the assessments noted will be performed. Additional assessments may be performed at the investigator’s discretion.
e Visit 1 for SP1042 will be the same as the Termination Visit of SP0994. Prior to or at Visit 1 of SP1042, the subject’s informed consent will be signed and 
eligibility assessed, concomitant medications including AEDs will be recorded, AEs will be assessed, and LCM dispensed (call to IXRS).
f If circumstances obligate the investigator to add an additional AED treatment as a function of safety (eg, seizure control), the subject must be withdrawn from 
the study but the additional AED may be added prior to the subject’s termination from the study if this treatment approach is in the best safety interest of the 
subject. The use of benzodiazepines as rescue for epilepsy is allowed if taken at a maximum frequency of once per week. The use of benzodiazepines for 
indications other than epilepsy rescue therapy is permitted.
g The designated procedures will serve as the point of data for both the Termination Visit of SP0994 and Visit 1 of SP1042.
h Urine pregnancy tests may be performed for all designated study visits.
i The IXRS should be called for any cases of dose adjustment.
j Dispensing of LCM will be done at the Termination Visit/Early Termination Visit only if tapering of LCM is required.
k If the subject reports an AE which could be due to a cardiac condition, an electrocardiogram (ECG) should be performed. Signs and symptoms of depression 
and/or suicidal ideation or suicidal behavior should be monitored as a part of the AE assessment.
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 46 of 48
Change #2
Section 8.2: Heading
Visit 2, 3, 4, 5, 6, 7 (Week 26, 52, 78, 104, 130, 156)-Treatment Visits
Has been changed to:
Visit 2, 3, 4, 5, 6 (Week 26, 52, 78, 104, 130)-Treatment Visits
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 47 of 48
16
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 
Date/S
Date/S
PY
This document cannot be used to support any marketing authorization
Signa
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application 
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UCB
01 Jul 2015
Clinical Study Protocol
Lacosamide
SP1042
Confidential
Page 48 of 48
17
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.
COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 

SAP_001.pdf: 
UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 1 of 19
 
STATISTICAL ANALYSIS PLAN 
Study: SP1042
Product: Lacosamide
A MULTICENTER, OPEN-LABEL, FOLLOW-UP STUDY TO ASSESS THE LONG-TERM
USE OF LACOSAMIDE (FLEXIBLE DOSE FROM 200 TO 600MG/DAY) USED AS 
MONOTHERAPY IN SUBJECTS WHO COMPLETED SP0994 AND RECEIVED 
LACOSAMIDE MONOTHERAPY TREATMENT
SAP/Amendment Number
Date
Final SAP
08 MAR 2016
Confidentiality Statement
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, reproduced, 
published, or otherwise used without the express permission of UCB.
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 2 of 19
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................4 
1 
INTRODUCTION .............................................................................................................5 
2 
PROTOCOL SUMMARY.................................................................................................5 
2.1 Study objective(s) ..............................................................................................................5 
2.2 Study variable(s) ................................................................................................................5 
2.2.1 
Safety variable(s)...................................................................................................5 
2.3 Study design and conduct ..................................................................................................5 
2.4 Determination of sample size.............................................................................................6 
3 
DATA ANALYSIS CONSIDERATIONS........................................................................7 
3.1 General presentation of summaries and analyses ..............................................................7 
3.2 General study level definitions ..........................................................................................7 
3.2.1 
Analysis time points ..............................................................................................7 
3.2.2 
Relative day ...........................................................................................................7 
3.3 Definition of Baseline values.............................................................................................8 
3.4 Protocol deviations.............................................................................................................8 
3.5 Analysis sets.......................................................................................................................8 
3.5.1 
Enrolled Set ...........................................................................................................8 
3.5.2 
Safety Set...............................................................................................................8 
3.6 Treatment assignment and treatment groups .....................................................................9 
3.7 Center pooling strategy......................................................................................................9 
3.8 Coding dictionaries ............................................................................................................9 
3.9 Changes to protocol-defined analyses................................................................................9 
4 
STATISTICAL/ANALYTICAL ISSUES.........................................................................9 
4.1 Adjustments for covariates.................................................................................................9 
4.2 Handling of dropouts or missing data................................................................................9 
4.2.1 
Incomplete dates for adverse events and concomitant medications ......................9 
4.2.2 
Incomplete dates for the last administration of study medication .......................10 
4.3 Interim analyses and data monitoring..............................................................................10 
4.4 Multicenter studies...........................................................................................................10 
4.5 Multiple comparisons/multiplicity...................................................................................10 
4.6 Use of an efficacy subset of subjects ...............................................................................11 
4.7 Active-control studies intended to show equivalence......................................................11 
4.8 Examination of subgroups ...............................................................................................11 
5 
STUDY POPULATION CHARACTERISTICS.............................................................11 
5.1 Subject disposition...........................................................................................................11 
5.2 Protocol deviations...........................................................................................................11 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................11 
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 3 of 19
6.1 Demographics ..................................................................................................................11 
6.2 Other Baseline characteristics..........................................................................................11 
6.3 Medical history and concomitant diseases.......................................................................11 
6.4 Concomitant medications.................................................................................................11 
6.5 Concomitant medical procedures.....................................................................................12 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................12 
8 
EFFICACY ANALYSES ................................................................................................12 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS..........................................12 
9.1 Pharmacokinetics .............................................................................................................12 
9.2 Pharmacodynamics ..........................................................................................................12 
10 SAFETY ANALYSES.....................................................................................................12 
10.1 Extent of exposure ...........................................................................................................12 
10.2 Adverse events.................................................................................................................13 
11 REFERENCES ................................................................................................................16 
12 APPENDICES .................................................................................................................17 
12.1 Other significant TEAEs..................................................................................................17 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE.....................................................19 
LIST OF TABLES
Table 12‒1: 
List of other significant TEAEs.......................................................................17 
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08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 4 of 19
LIST OF ABBREVIATIONS
AE
adverse event
AED
antiepileptic drug
ATC
Anatomical Therapeutic Chemical
CBZ-CR
carbamazepine (controlled release)
CRF
case report form
CSR
Clinical Study Report
ES
Enrolled Set
IP
Investigational Product
IXR
interactive voice/web response system
LCM
lacosamide
MedDRA®
Medical Dictionary for Regulatory Activities
PT
Preferred Term
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
Standard deviation
SOC
System Organ Class
SS
Safety Set
TEAE
treatment-emergent adverse event
WHO-DRL
World Health Organization-Drug Reference
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08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 5 of 19
1
INTRODUCTION
This document outlines the planned analyses to support the SP1042 clinical study report (CSR).
2
PROTOCOL SUMMARY
2.1
Study objective(s)
The primary objective of the study is to assess the long-term safety and tolerability of lacosamide 
(LCM) dosed at 200mg/day to 600mg/day when used as monotherapy in subjects, with partial-
onset seizures or generalized tonic-clonic seizures (without clear focal origin), who completed 
SP0994 and received LCM.
2.2
Study variable(s)
2.2.1
Safety variable(s)
The primary safety variables are as follows:
x
Adverse events (AEs) reported spontaneously by the subject and/or caregiver or observed by 
the investigator
x
Withdrawals due to AEs
x
Serious adverse events (SAEs)
2.3
Study design and conduct
SP1042 is a long-term, open-label, follow-up study for subjects being treated with LCM 
monotherapy at the time of unblinding of SP0994. Subjects in SP0994 who were receiving LCM 
will have the opportunity to participate in SP1042 and will have access to open-label follow-up
treatment with LCM. Subjects who were receiving carbamazepine (controlled realease) 
(CBZ-CR) or who were in LCM taper in SP0994 at the time of unblinding will not be allowed to 
participate in SP1042. Subjects who do not wish to continue LCM therapy after unblinding of 
SP0994 will be tapered off LCM and will not participate in SP1042.
Visit 1 for SP1042 will be the same as the Termination Visit of SP0994. Clinic visits are 
scheduled approximately every 26 weeks relative to the SP1042 Visit 1 date. Dose modifications 
required for optimization of seizure control or tolerability issues will be addressed in 
Unscheduled Visits or regularly scheduled visits. A visit window of ±7 days relative to Visit 1 is 
applicable for all regularly scheduled visits.
In SP0994, subjects will be receiving a dose of LCM 200mg/day, 300mg/day, 400mg/day, 
500mg/day, or 600mg/day and will continue to receive the same dose in SP1042 until further 
dose adjustments are required.
During SP1042 visits, investigators will be allowed to increase or decrease the dose of LCM to 
optimize tolerability and seizure control for each subject. The investigator may maintain the 
subject’s LCM dose, decrease the dose in decrements of 100mg/day per week to a minimum 
dose of LCM 200mg/day, or increase the dose in increments of 100mg/day per week up to a 
maximum dose of LCM 600mg/day. Lacosamide doses administered in this study must be from 
200mg/day to 600mg/day, must comply with doses that can be administered with LCM 50mg 
tablets, and should be a dose that can be administered in equal divided doses twice daily. The 
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 6 of 19
interactive voice/web response system (IXRS) should be called any time there is a dose increase 
or dose reduction.
If, in the investigator’s opinion, a lower dose of LCM is medically more suitable for a subject, 
the decision to allow such patients to continue in the study on a lower dose of LCM will be made 
based on appropriate medical justification and after prior discussion with the study Medical 
Monitor.
In order to continue study participation, subjects must maintain treatment with LCM 
monotherapy.
Subjects who discontinue prematurely from SP1042 and who will not continue further treatment 
with LCM should gradually taper LCM following an Early Termination Visit. These subjects 
will perform an Early Termination Visit followed by the visits required for the End-of-Study 
Phase. Subjects should be tapered off LCM at recommended decreasing steps of 
200mg/day/week. A slower taper (eg, 100mg/day/week) or faster taper is permitted, if medically 
necessary; however, the maximum duration of tapering should not exceed 6 weeks. Subjects will 
attend a Final Visit 2 weeks after the final dose of LCM. In the case of LCM withdrawal and 
taper, the investigator is allowed to add any other antiepileptic drug (AED) during the End-of-
Study Phase, following the investigator’s medical judgment.
Subjects who discontinue from the study as a result of requiring treatment with other AEDs will 
return for an Early Termination Visit, and may be prescribed LCM by their physician (ie, not 
supplied by UCB) as adjunctive therapy if LCM is well tolerated by the subject (dose should be 
adapted as per investigator’s judgment). The Early Termination Visit will be the last study visit 
for these subjects.
A Termination Visit will be performed for subjects who are ongoing in the Treatment Phase at 
the time that the marketing application is approved and LCM is commercially available for 
monotherapy in the subject’s country, or UCB has determined that the clinical development 
program for the monotherapy indication will be formally discontinued, or up to a maximum 
period of 3 years, whichever is earlier. Subjects may be immediately prescribed commercially 
available LCM. In this instance, the Termination Visit will be the last study visit completed by 
the subject. If subjects do not continue with LCM treatment, following the Termination Visit, 
subjects will be tapered off LCM. The Final Visit will be conducted 2 weeks after the final dose 
of LCM.
Subjects will be allowed to continue treatment in this study until marketing application is 
approved and LCM is commercially available for monotherapy in the subject’s country, or UCB 
has determined that the clinical development program for the monotherapy indication will be 
formally discontinued, or up to a maximum period of 3 years, whichever is earlier. The 
maximum total duration of the study will be 164 weeks, including up to a 156-week Treatment 
Phase duration and up to an 8-week End-of-Study Phase.
The end of the study is defined as the date of the last visit of the last subject in the study.
2.4
Determination of sample size
No formal sample size calculations have been performed for this study as there are no statistical 
hypotheses being tested. The sample size will be determined by the number of subjects in 
SP0994 who have been treated with LCM that are eligible to enter this open-label follow-up
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 7 of 19
study. It is anticipated that approximately 150 subjects who receive LCM in SP0994 will 
participate in this follow-up study.
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 or higher. All tables and listings will use Courier 
New font size 9.
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 one 
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 n, mean, standard deviation (SD), 
median, minimum, and maximum.
Decimal places for descriptive statistics will always apply the following rules:
x
“n” will be an integer.
x
Mean, SD and median will use 1 additional decimal place compared to the original data.
x
Minimum and maximum will have the same number of decimal places as the original value.
Unless otherwise specified, all analysis will be performed for the Safety Set (SS).
A complete set of data listings containing all documented data and all calculated data will be 
generated.
3.2
General study level definitions
3.2.1
Analysis time points
x
Treatment Period: the start of the Treatment Period is the date of Visit 1. The end of the 
Treatment Period is the date of the Termination Visit or Early Termination Visit for subjects 
who are prematurely discontinued. For subjects who discontinued during the Treatment 
Period without an Early Termination Visit, the end of the Treatment Period is the date of last 
known visit date (including unscheduled visits), the date of last dose, the date of premature 
termination, or the date of final contact, whichever is the latest.
x
End of Study Period: the day following the last day in the Treatment Period to the Final Visit, 
including tapering. Any additional data collected during the study but after the Final Visit 
will also be included in the End of Study Period.
3.2.2
Relative day
Relative day will be presented in subject data listings. Relative day will be calculated as follows:
x
If the start (stop) date occurred prior to the first intake of LCM in SP1042, the relative day is 
calculated as start (stop) date minus first LCM dose date. In subject data listings, relative 
days based on this situation will be preceded by a ‘-’.
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 8 of 19
x
If the start (stop) date occurred on or after the first intake of LCM but prior to the last dose of 
LCM in SP1042, the relative day is calculated as start (stop) date minus first LCM dose date 
+ 1.
x
If the start (stop) date occurred after the date of last dose of LCM in SP1042, the relative day 
is calculated as start (stop) date minus last dose date. In subject data listings, relative days 
based on this situation will be preceded by a ‘+’.
3.3
Definition of Baseline values
Baseline will be the Baseline values in SP0993. Only date of birth and gender will be collected 
for SP1042 when applicable.
3.4
Protocol deviations
Important protocol deviations are deviations from the protocol that could potentially have a 
meaningful impact on study conduct or on the key safety outcomes for an individual subject. The 
criteria for identifying important protocol deviations and the classification of important protocol 
deviations will be defined within the appropriate protocol-specific document (eg, the Protocol 
Deviation Specification). 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.
In general, the protocol deviations will be considered according to the following general 
categories:
x
Informed Consent
x
Inclusion/Exclusion criteria
x
Withdrawal criteria
x
Investigational Product (IP) / Study treatment
x
Disallowed medications
x
AE / SAE
x
Visit schedule
x
Procedure / Test
x
Other
Important protocol deviations will be reviewed as part of the ongoing data cleaning process prior 
to database lock.
3.5
Analysis sets
3.5.1
Enrolled Set
The Enrolled Set (ES) will consist of all subjects who have given informed consent in SP1042.
3.5.2
Safety Set
The SS will consist of all subjects in the ES who have received at least 1 dose of study 
medication in SP1042. 
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 9 of 19
3.6
Treatment assignment and treatment groups
This is a follow-up study to assess the long-term use of LCM used as monotherapy in subjects 
who completed SP0994. Subjects treated with LCM monotherapy in SP0994 will continue to be 
treated with LCM.
Analysis will be performed overall as only subjects treated by LCM will be enrolled.
3.7
Center pooling strategy
Centers will be pooled by country and region for the purpose of disposition analysis. Countries 
will be pooled as follows:
Europe: Bulgaria, Finland, France, Germany, Latvia, Poland, Russia, Sweden, Switzerland, 
Ukraine;
North America: Mexico;
Asian Pacific: Japan, Philippines, South Korea.
3.8
Coding dictionaries
Medical history and AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA 16.1 or higher). Medications will be coded using the World Health Organization Drug 
Reference List (WHO-DRL SEP/2013 or higher). Medical procedures will not be coded.
3.9
Changes to protocol-defined analyses
Not applicable.
4
STATISTICAL/ANALYTICAL ISSUES
4.1
Adjustments for covariates
No adjustments of covariates will be applied.
4.2
Handling of dropouts or missing data
No imputation of missing values associated with an individual date or visit is planned, with the 
exception of incomplete and missing dates specified in the following section. With respect to 
AEs, events with missing severity will be assumed to be severe. Events with a missing 
relationship to study medication per the investigator will be assumed to be related.
For evaluation of safety variables, subjects who prematurely discontinue the study will be 
evaluated based on the data collected at each visit attended.
4.2.1
Incomplete dates for adverse events and concomitant medications
In order to correctly identify an AE or medication as occurring during an analysis period, a 
complete date must be established. The algorithm listed below will be followed to impute 
incomplete or missing start dates for AEs and concomitant medications. In subject data listings, 
start dates of AEs or medications will be displayed as reported (ie, no imputed dates will be 
displayed).
x
Missing start day, but month and year present
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08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 10 of 19
If the start date of study medication in SP1042 occurred in the same month and year as the 
occurrence of the AE or medication, the start date of the AE or medication will be assigned to 
the day of first dose of study medication in SP1042.
Otherwise the start date will be set to the 1st day of the month.
x
Missing start day and month, but year present
If the start date of study medication in SP1042 occurred in the same year as the occurrence of the 
AE or medication, the start date of the AE or medication will be assigned to the day of first dose 
of study medication in SP1042.
Otherwise the start date will be set to January 1st.
x
Complete missing start date
If the start date is completely missing and the stop date is unknown or not prior to the first dose 
of study medication in SP1042, the start date will be assigned to the date of first dose of study 
medication in SP1042.
4.2.2
Incomplete dates for the last administration of study medication
The complete date of last administration of study medication must be established in order to 
calculate the duration of exposure. The algorithm listed below will be followed to impute 
incomplete or missing date of the last administration of study medication.
x
Missing day of the last administration, but month and year present
The date of last administration will be set to the last day of the month or the date of the final 
contact, whichever is earlier in the month.
x
Missing day and month of the last administration but year present
The date of last administration will be set to December 31st of the year or the date of the final 
contact, whichever is earlier in the year.
x
Completely missing the date of the last administration
The date of last administration will be set to the date of final contact.
If the imputed date of last administration according to the rules above is after the date of a death, 
the date of last administration will be set to the date of death.
4.3
Interim analyses and data monitoring
No formal interim analysis or data monitoring is planned in the study. However, interim data 
may be reported prior to the completion of this study to support annual reports, regulatory
submissions, and publications.
4.4
Multicenter studies
No analysis per center is foreseen due to the small number of subjects recruited per center.
4.5
Multiple comparisons/multiplicity
Not applicable for this study.
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08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 11 of 19
4.6
Use of an efficacy subset of subjects
Not applicable for this study.
4.7
Active-control studies intended to show equivalence
Not applicable for this study.
4.8
Examination of subgroups
No subgroup analysis is planned.
5
STUDY POPULATION CHARACTERISTICS
5.1
Subject disposition
The number of subjects in the ES and SS will be presented overall, by region (Europe, North 
America, and Asian Pacific), by country and by investigator. The date of first subject in and date 
of last subject out will also be included for each investigator.
The number and percentage of subjects who completed and discontinued from the study with 
associated reasons for discontinuation will be summarized for the SS.
In addition, the number and percentage of subjects who discontinued due to AE will be 
summarized to address the EudraCT requirement.
5.2
Protocol deviations
Number and percentage of subjects with important protocol deviations will be summarized by
the categories defined in Section 3.4 for the SS. Subjects will not be excluded from the SS 
because of important protocol deviations. All important protocol deviations will be listed in the 
subject data listing.
6
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS
6.1
Demographics
Demographics will be summarized for the SS:
x
Age (years) at SP1042 entry – continuous and categorized (18 to  < 65 years; 65 to <85 
years; ≥85 years and ≤18 years; ≥19 to <65 years ; ≥ 65 years)
x
Gender (male, female)
6.2
Other Baseline characteristics
No other Baseline characteristics will be collected and analyzed.
6.3
Medical history and concomitant diseases
No analysis will be performed in SP1042.
6.4
Concomitant medications
Medications will be summarized using the Anatomical Therapeutic Chemical (ATC) codes from 
the WHO-DRL dictionary. All tabulations will be sorted by frequency of the higher level ATC 
code and by frequency of the lower level ATC code within the higher level ATC code.
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08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 12 of 19
Concomitant medications are medications reported on the Concomitant Medications case report 
form (CRF) page or on the Concomitant Medications ongoing from study SP0994 CRF page 
taken on or after the first dose of study medication and the start date is not after the date of last 
dose in SP1042. If the date of last dose is unknown, any medications taken on or after the first 
dose of study medication will be considered as concomitant medications. 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.
Antiepileptic drugs (AEDs) are medications reported on the Concomitant Medications CRF page 
or on the Concomitant Medications ongoing from study SP0994 CRF page, with indications 
related to epilepsy or seizure. Antiepileptic drugs will be summarized separately from the other 
medications (non-AEDs).
Concomitant AEDs during the study will be presented by 4-level ATC (4-digit) terms and 
preferred medication name. Concomitant non-AED medications will be summarized separately 
by 1-level and 2-level ATC (3 digit) terms.
A glossary of ATC codes and associated investigator’s terms for all medications will also be 
listed.
6.5
Concomitant medical procedures
Concomitant medical procedures will be listed by subject.
7
MEASUREMENTS OF TREATMENT COMPLIANCE
Subjects identified to have non-protocol LCM dosing will be summarized in tabular format 
under the protocol deviations category of LCM Dosing Regimen (See Section 3.4). Information 
reported on the CRF regarding tablets dispensed and returned will be reported in subject data 
listings. LCM dosing compliance will be evaluated through the review of important protocol 
deviations classified under LCM Dosing Regimen (See Section 3.4).
8
EFFICACY ANALYSES
Not applicable for this study.
9
PHARMACOKINETICS AND PHARMACODYNAMICS 
9.1
Pharmacokinetics
Not applicable for this study.
9.2
Pharmacodynamics
Not applicable for this study.
10
SAFETY ANALYSES
Safety analyses will be performed in the SS.
10.1
Extent of exposure
Overall exposure to LCM in days during the Treatment Period is calculated as the date of last 
administration of LCM minus the date of first administration in SP1042 plus 1.
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 13 of 19
Subject-years of exposure will be calculated as the number of days of exposure, divided by 
365.25.
Gaps in LCM treatment or days on the LCM dosing log CRF with unknown dosing will not be 
subtracted from the overall exposure days and subject-years of exposure.
LCM modal dose (mg/day) will be defined as the daily LCM dose the subject received for the 
longest duration during the Treatment Period. The modal dose calculation is based on the 
number of days a subject was on a given daily dose. Gaps in LCM dosing will be excluded from 
the determination of modal dose (ie, no imputation for days with missing dosing log information 
will be performed).
The maximum daily dose will be calculated as the highest total daily dose the subject received 
during the treatment period. 
The following exposure summaries and a listing will be produced:
x
Number of subjects and subject-years of exposure by cumulative time intervals (months) (ie, 
>0, >=6, >=12, >=18, >=24, >=30, >=36, where one month is defined as 28 days). The 
categories of intervals may be adjusted according to the actual data
x
Summary statistics for modal dose, maximum daily dose and duration of exposure
x
Summary statistics for duration of exposure and subject-years of exposure by modal dose and 
by maximum daily dose cohorts
x
Number and percentage of subjects within each LCM treatment duration category by modal 
dose and by maximum daily dose cohorts. LCM treatment duration categories (days) are as 
follows: 1 to 84, 85 to 168, 169 to 336, 337 to 504, 505 to 672, 673 to 840, 841 to 1008, 
>1008, and any duration. The categories may be adjusted according to the actual data.
10.2
Adverse events
The primary safety variables are as follows:
x
AEs reported spontaneously by the subject and/or caregiver or observed by the investigator
x
Withdrawals due to AEs
x
SAEs
Treatment-emergent adverse events (TEAEs) are defined as AEs that started on or after the date 
of first dose of study medication in SP1042 and within 30 days following the date of last study 
medication administration, or AEs whose intensity worsened on or after the date of first dose of 
study medication and within 30 days following the date of last dose. If the date of the last dose of 
study medication is unknown, any AEs occurring on or after the first dose of study medication 
will be considered treatment-emergent.
TEAEs will be assigned to an analysis period based on the AE onset dates. AEs will be tabulated 
by MedDRA system organ class (SOC) and MedDRA preferred term (PT). The number and 
percentage of subjects experiencing each event at least once will be summarized. Numbers of 
individual AE occurrences will be also presented in selected tables. All summaries will be sorted 
alphabetically by SOC and by decreasing frequency of events within SOC.
The following summaries will be presented for the AEs:
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 14 of 19
x
Ongoing AEs at SP1042 study entry.
x
Adverse events during the Treatment Period:

An overview summary of TEAEs during the Treatment Period will be presented. It will 
include the numbers and percentages of subjects with at least one TEAE, at least one 
Serious TEAE, at least one TEAE leading to discontinuation, at least one drug-related 
TEAE, at least one severe TEAE, and death.

Incidence of TEAE during the Treatment Period.

Incidence of TEAEs by maximum intensity during the Treatment Period. If the intensity 
of an AE is missing, it will be assumed to be severe.

Incidence of TEAEs during the Treatment Period by maximum relationship per 
investigator. If the relationship is missing, the AE will be assumed to be related to study 
medication.

Subject number listing for TEAEs during the Treatment Period

Incidence of Serious TEAEs during the Treatment Period

Subject number listing for Serious TEAEs during the Treatment Period

Incidence of TEAEs leading to discontinuation during the Treatment Period

Subject number listing for TEAEs leading to discontinuation during the Treatment Period

Incidence of other significant TEAEs during the Treatment Period. Other significant 
TEAEs are defined by the MedDRA terms in Appendix 12.1.

Subject number listing for other significant TEAEs during the treatment period

Incidence of TEAEs during the Treatment Period per 100 Subject-months.
x
Adverse events during the study (including the Treatment and End of Study Periods)

Overview of TEAEs during the study
x
Adverse events by relationship during  the study

Incidence of TEAEs during the study by relationship to study drug per investigator

Incidence of serious TEAEs during the study by relationship to study drug per 
investigator

Incidence of non-serious TEAEs during the study by relationship to study drug per 
investigator

Incidence of non-serious TEAEs occurring in >5% of subjects during the study by 
relationship to study drug per investigator

Incidence of fatal TEAEs during the study by relationship to study drug per investigator
x
Subject number listing for all deaths
Individual subject data listings will be presented for all AEs in the SP1042 clinical database, 
serious AEs, AEs leading to death, TEAEs leading to discontinuation, and other significant AEs. 
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 15 of 19
A glossary of MedDRA terms and associated investigator’s terms for TEAEs will also be 
presented.
REDACTED COPY 
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 16 of 19
11
REFERENCES
No reference.
REDACTED COPY 
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 17 of 19
12
APPENDICES
12.1
Other significant TEAEs
Table 12‒1: List of other significant TEAEs
MedDRA Preferred Term
HEPATOTOXICITY RELATED TERMS
Hepatitis toxic
Hepatotoxicity
CARDIAC AND ECG RELATED TERMS
Atrioventricular block complete
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 behaviour
Suicidal ideation
Suicide attempt
Intentional self-injury
Self injurious behaviour
Self-injurious ideation
Intentional overdose
Poisoning deliberate
ADDITIONAL TERMS
REDACTED 
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 18 of 19
Table 12‒1: List of other significant TEAEs
MedDRA Preferred Term
Loss of consciousness
Syncope
* All cases with reported reduced heart rate will be reviewed and only cases with marked bradycardia (marked 
reduction in heart rate) with HR <45 bpm will be listed.
REDACTED COPY 
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UCB
08 Mar 2016
Statistical Analysis Plan
Lacosamide
SP1042
Confidential
Page 19 of 19
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution.
COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.