A Noninterventional Study of Vimpat® (Lacosamide) as Adjunctive Antiepileptic Drug Therapy in Patients With Brain Tumor-related Epilepsy
Conditions: Brain Tumor Related Epilepsy (BTRE)
Sponsor: UCB BIOSCIENCES GmbH

UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 1 of 35
NONINTERVENTIONAL STUDY 
OBSERVATIONAL PLAN EP0045 AMENDMENT 1
A NONINTERVENTIONAL STUDY OF VIMPAT® (LACOSAMIDE) 
AS ADJUNCTIVE ANTIEPILEPTIC DRUG THERAPY IN 
PATIENTS WITH BRAIN TUMOR-RELATED EPILEPSY
(VIBES)
UCB BIOSCIENCES GMBH
ALFRED-NOBEL-STRASSE 10
40789 MONHEIM
GERMANY
Final Noninterventional Study Observational Plan 
23 Jun 2014
Noninterventional Study Observational Plan Amendment 1
01 Jun 2015
Confidentiality Statement
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published or otherwise used without the express permission of UCB.
REDACTED COPY 
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 2 of 35
STUDY CONTACT INFORMATION 
Sponsor 
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Clinical Project Manager
Name:
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Email:
Study Physician
Name:
, MD
Address:
UCB Pharma S.A.
Allée de la Recherche 60
1070 Brussels
BELGIUM
Phone:
Fax:
Email:
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 3 of 35
Lead Clinical Development Representative
Name:
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Email:
Medical Affairs Medical Director
Name:
Address:
UCB Pharma GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Email:
Clinical Trial Biostatistician
Name:
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Email:
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 4 of 35
Contact information for adverse drug reaction reports (24h), adverse 
events of special interest (24h), safety relevant reports, and pregnancy
reports
COUNTRY
FAX NUMBER
E-MAIL ADDRESS
France
+33 1 4729 4591
pharmacovigilance-fr@ucb.com
Germany
+49 2173 48 2010
ds.de@ucb.com
Italy
+39 02 30079 246
ds.it@ucb.com
Netherlands
+31 76 587 5264
ds.nl@ucb.com
Spain
+34 91 57 22572
drugsafetyspain@ucb.com
UK
+44 1753 447858
dsuk@ucb.com
Clinical Monitoring Contract Research Organization
Name:
PRA GmbH
Address:
Gottlieb-Daimler-Strasse 10
68165 Mannheim
GERMANY
Phone:
+49 621 8782 0
Fax:
+49 621 8782 184
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 5 of 35
DECLARATION AND SIGNATURE OF TREATING PHYSICIAN
I confirm that I have carefully read and understood this noninterventional study observational 
plan and agree to conduct this study as outlined in this noninterventional study observational 
plan and local laws and requirements.
I will ensure that all physicians and other staff members read and understand all aspects of this 
noninterventional study observational plan.
I received and have read all study-related information provided to me.
The objectives and content of this noninterventional study observational plan 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 BIOSCIENCES GmbH.
All rights of publication of the results reside with UCB BIOSCIENCES GmbH, unless other 
agreements were made in a separate contract.
Treating physician
<Insert name> 
_____________________________
Date/Signature
REDACTED COPY 
ion and any extensions or variations thereof. 
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_____
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 6 of 35
TABLE OF CONTENTS
STUDY CONTACT INFORMATION .....................................................................................2
DECLARATION AND SIGNATURE OF TREATING PHYSICIAN ....................................5
LIST OF ABBREVIATIONS....................................................................................................8
1
RATIONALE FOR THE STUDY.....................................................................................9
2
STUDY TYPE .................................................................................................................10
3
STUDY OBJECTIVES....................................................................................................10
4
STUDY VARIABLES.....................................................................................................10
4.1
Primary variables ...................................................................................................10
4.2
Secondary variables ...............................................................................................10
4.3
Safety variables......................................................................................................11
5
STUDY DESIGN.............................................................................................................11
6
EXPECTED STUDY DURATION.................................................................................12
7
ANTICIPATED REGIONS AND COUNTRIES............................................................12
8
SELECTION AND WITHDRAWAL OF PATIENTS ...................................................12
8.1
Selection criteria ....................................................................................................12
8.2
Withdrawal criteria ................................................................................................13
9
STUDY TREATMENT(S) ..............................................................................................13
9.1
Numbering of patients............................................................................................13
10
ASSESSMENT OF SAFETY..........................................................................................13
10.1
Adverse events and adverse drug reactions ...........................................................14
10.1.1
Definitions of adverse events and adverse drug reactions...........................14
10.1.2
Reporting and description of adverse events ...............................................14
10.1.3
Follow up on adverse events........................................................................14
10.1.4
Pregnancy.....................................................................................................15
10.1.5
Overdose of lacosamide...............................................................................15
10.1.6
Safety signal detection.................................................................................15
10.1.7
Procedures for reporting adverse events and adverse drug reactions ..........15
10.1.8
Adverse events of special interest................................................................16
11
STATISTICS ...................................................................................................................17
11.1
Definition of analysis sets......................................................................................17
11.2
General statistical considerations...........................................................................17
11.3
Planned analyses ....................................................................................................18
11.3.1
Analysis of the primary variable..................................................................18
11.3.2
Analysis of secondary variables ..................................................................18
11.3.3
Subgroup analyses .......................................................................................19
11.3.4
Analysis of safety variables.........................................................................19
11.4
Planned interim analysis and data monitoring.......................................................19
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 7 of 35
11.5
Determination of sample size.................................................................................19
12
STUDY MANAGEMENT AND ADMINISTRATION.................................................20
12.1
Quality assurance...................................................................................................20
12.1.1
Monitoring ...................................................................................................20
12.1.2
Data handling...............................................................................................20
12.1.2.1
Case Report form completion ............................................................20
12.1.2.2
Database entry and reconciliation......................................................20
12.2
Termination of study..............................................................................................20
12.3
Data archiving........................................................................................................21
12.4
Legal provisions and ethics....................................................................................21
12.4.1
Data protection and data privacy declaration ..............................................21
12.4.2
Report of the Ethics Committee...................................................................21
12.4.3
Notification/submission to relevant Regulatory Authority(ies)...................21
12.4.4
Legally required reports...............................................................................21
13
REMUNERATION..........................................................................................................22
14
FINAL REPORT AND PUBLICATION ........................................................................22
15
RECOMMENDED SCHEDULE OF STUDY ASSESSMENTS...................................23
16
REFERENCES ................................................................................................................25
17
APPENDICES .................................................................................................................26
17.1
NIS Observational Plan Amendment 1..................................................................26
18
DECLARATIONS AND SIGNATURES .......................................................................35
LIST OF TABLES
Table 15‒1:
Recommended schedule of study assessments ............................................23
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 8 of 35
LIST OF ABBREVIATIONS
ADR
adverse drug reaction
AE
adverse event
AED
antiepileptic drug
AESI
adverse event of special interest
BTRE
brain tumor-related epilepsy
CGIC
Clinical Global Impression of Change
CI
confidence interval
eDF
electronic Documentation form
EMA
European Medicines Agency 
EQ-5D-5L
5-Level EuroQol-5 Dimension Quality of Life Assessment
ES
Enrolled Set
FAS
Full Analysis Set
HLT
High Level Term
LCM
lacosamide
MDASI-BT
M.D. Anderson Symptom Inventory - Brain Tumor 
MedDRA®
Medical Dictionary for Regulatory Activities 
NIS
noninterventional study
PGIC
Patient Global Impression of Change
PT
preferred term
QoL
quality of life
SOC
system organ class
SS
Safety Set
ULN
upper level of normal 
VAS
visual analogue scale
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 9 of 35
1
RATIONALE FOR THE STUDY
Patients with brain tumor-related epilepsy (BTRE) present a complex therapeutic profile and 
require a unique and multidisciplinary approach. There are many factors to take into 
consideration, especially the management of epilepsy, which is often considered the most 
important risk factor for long-term disability (Maschio, 2012).
In patients with brain tumors, seizures are the onset symptom in 20-40% of patients, while a 
further 20-45% of patients will present with seizures during the course of the disease. Overall, 
the incidence of epilepsy in brain tumors, regardless of histological type and anatomical site of 
the lesion, varies from 35 to 70% (Rossetti and Stupp, 2010; Vecht and Wilms, 2010; Singh et al, 
2007; Hildebrand et al, 2005; Wen and Marks, 2002; Glantz et al, 2000).
Lacosamide (LCM, VIMPAT®) is an antiepileptic drug (AED), which has been shown to provide 
a favorable benefit-risk profile and was approved by the European Medicine Agency (EMA) on 
29 Aug 2008 (EU/1/08/470/01 to 013 and EU/1/08/470/016 to 023; EMA reference 
EMEA/H/C/000863) as adjunctive therapy in the treatment of partial-onset seizures with or 
without secondary generalization in patients with epilepsy aged 16 years and older (film-coated 
tablets of 50mg, 100mg, 150mg, and 200mg, syrup of 10mg/mL, and solution for infusion of 
10mg/mL). In addition to the European Union, LCM is approved as adjunctive therapy in adults 
suffering from partial-onset seizures in at least 38 other countries to date. In the United States, 
LCM is approved as adjunctive therapy or monotherapy in patients age 17 years and older and 
suffering from partial-onset seizures.
The pharmacokinetic profile of LCM includes minimal cytochrome P450 interaction and low 
(<15%) protein binding, resulting in a low risk for drug-drug interaction (Lacosamide Summary 
of Product Characteristics, 2011). This is particularly important in the context of BTRE, since 
many chemotherapeutic agents are susceptible to metabolism via the P450 pathway, as are a 
number of AEDs which may be co-prescribed during the natural history of disease.
Lacosamide has been shown to be efficacious and generally well tolerated in real life clinical 
practice, from first adjunct to later treatment lines (Stephen et al, 2011; Villanueva et al, 2012).
The first noninterventional study (NIS) evaluating the use, effectiveness, and tolerability of LCM
in routine clinical practice (VImpaT added to One Baseline AED, VITOBA, ClinicalTrials.gov 
NCT01098162) started in Germany in May 2009 in about 550 patients with less difficult-to-treat 
disease, excluding a complex therapeutic profile like patients with BTRE, and being treated with 
only a single Baseline AED. The Observation Period per patient in the VITOBA study was 
6 months. The results of the second interim analysis based on >300 patients indicate improved 
seizure control with a favorable safety and tolerability profile when LCM is used as adjunctive 
treatment to AED monotherapy in routine clinical practice (Noack-Rink et al, 2012). 
There are limited data available in patients with complex-to-treat diseases like BTRE, as well as 
limited established guidance. However, general consensus is that nonenzyme inducing AEDs, 
like LCM, should be preferred because chemotherapy and steroids are the main treatment in this 
population, and both are affected by enzyme inducers. 
The most important published uses of LCM in this population are a retrospective analysis 
including 70 patients in 5 US centers (Saria et al, 2013) and prospective case series including 
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 10 of 35
14 patients in Italy (Maschio et al, 2011), both of which show good tolerability and effectiveness 
of LCM in this subpopulation.
To better evaluate the use of LCM in patients with BTRE in routine clinical practice, a new 
observational study is necessary. The present study (EP0045) will significantly add to the 
published experience, and hopefully lead to the possibility of informed design of comparative 
studies, which is currently not possible due to the paucity of data in this area.
EP0045 is a multicenter, prospective NIS conducted at specialized sites in approximately 
6 European countries, with a 6-month Observation Period. Lacosamide will be added to any 
AED therapy (1 or 2 AEDs) in approximately 100 patients with BTRE.
The primary objective of this study is to evaluate in routine clinical practice the effectiveness of 
LCM added to 1 or 2 AEDs in the treatment of patients with BTRE due to low-grade glioma. 
The secondary objective of this study is to evaluate the tolerability and quality of life (QoL) of 
patients with BTRE due to low-grade primary brain tumor who are treated with LCM added to 
1 or 2 AEDs.
This observational study is entirely noninterventional. Patients will receive their usual medical 
care, which may include but is not limited to diagnostic or therapeutic procedures and medical 
treatment. The decision for initiating LCM therapy will be independent of study participation.
The patient (or legal representative) will be required to provide written informed consent for the 
use of his/her medical data before enrolling in the study.
2
STUDY TYPE
EP0045 is a multicenter NIS conducted at specialized sites in approximately 6 European 
countries.
3
STUDY OBJECTIVES
The primary objective of this study is to evaluate the effectiveness and patient global impression 
of LCM added to 1 or 2 AEDs in the treatment of patients with BTRE due to low-grade primary 
brain tumor. 
The secondary objective of this study is to evaluate the tolerability and QoL of patients with 
BTRE due to low-grade primary brain tumor who are treated with LCM added to 1 or 2 AEDs.
4
STUDY VARIABLES
4.1
Primary variables
The following primary variables will be measured:

Response at the end of the 6-month Observation Period, where a responder is a patient 
experiencing a 50% or greater reduction in partial-onset seizure frequency from Visit 1 
(Baseline) to Visit 3 (Month 6 or end of Observation Period)

Patient Global Impression of Change (PGIC) rating at Visit 3 (Month 6 or end of 
Observation Period)
4.2
Secondary variables
The following secondary variables will be measured:
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 11 of 35

Retention on LCM at the end of the 6-month Observation Period 

Time to discontinuation of LCM treatment from the date of first dose of LCM 

Change from Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period) in the 
5-Level EuroQol-5 Dimension Quality of Life Assessment (EQ-5D-5L) visual analogue scale 
(VAS) score and change in utility as converted from the 5 dimensions

Change from Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period) in the 
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)

Actual change from Visit 1 (Baseline) to Visit 3 (Month 6 or end of Observation Period) in 
seizure frequency (seizures per 28 days)

Percentage change from Baseline in seizure frequency 

Seizure-free status (Yes/No) at the end of the 6-month Observational Period

Discontinuation rate of LCM due to adverse drug reactions (ADRs)

Discontinuation rate of LCM due to lack of effectiveness

Clinical Global Impression of Change (CGIC) rating at Visit 3 (Month 6 or end of 
Observation Period)
4.3
Safety variables
The following safety variables will be collected:

Occurrence of ADRs or adverse events of special interest (AESIs) spontaneously reported by 
the patient or observed by the treating physician

Patient withdrawal due to ADRs
5
STUDY DESIGN
EP0045 is a multicenter, prospective, single-arm NIS conducted at specialized sites utilizing 
LCM added to existing treatment with 1 or 2 Baseline AEDs in patients ≥16 years of age with 
BTRE secondary to low-grade tumor. There are expected to be approximately 100 patients 
enrolled in the study (see Section 11.5). 
The patients will be followed as per current clinical practice for their condition. No additional 
diagnostic or monitoring procedures will be applied. The choices of AED treatment are made
independently by the treating physician in the regular course of practice and are, therefore, 
independent of participation in this NIS.
The observation of the first patient will start after a positive opinion to conduct the study has 
been received by the responsible ethics committee(s) (Section 12.4.2) and the regulatory 
authority(ies) if applicable (Section 12.4.3).
Eligible patients will be enrolled consecutively and all patients (and/or their parents or legal 
representatives) have to accept in writing that his/her medical data will be used for the evaluation 
of the study results by signing a study-specific Patient Data Consent form according to local 
requirements.
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 12 of 35
The clinical evaluation of patients with BTRE secondary to low-grade tumor will be performed 
by the treating physician following routine clinical practice. All visits and assessments will be 
scheduled and conducted per routine clinical practice. It is anticipated that visits will occur every 
3 months based on standard of care; therefore, each patient will have approximately 3 visits 
during their participation in this study. These visits will consist of:

Visit 1, Baseline

Visit 2, approximately 3 months after Baseline according to routine practice

Visit 3, approximately 6 months after Baseline according to routine practice or end of 
Observation Period
Patients who discontinue early should perform Visit 3 assessments as a Withdrawal Visit.
All data to be collected at Visits 1, 2, and 3 are described in Section 15, Table 15‒1 (to be 
collected as available). The management and reporting of ADRs and AESIs will be handled 
according to international drug safety regulations and UCB procedures.
Documentation of all study assessments is to be performed by the treating physician in the 
study-specific electronic Documentation form (eDF). Although the study is noninterventional in 
nature, every attempt must be made to assess all participating patients in the same way.
6
EXPECTED STUDY DURATION
The planned number of patients is 100 (see Section 11.5), with 93 evaluable patients expected. 
Approximately 25 specialized centers are planned for participation. The expected recruitment 
period is 12 months.
The Observation Period per patient will be up to 6 months after initiation of LCM treatment.
7
ANTICIPATED REGIONS AND COUNTRIES
The study will be conducted in approximately 6 European countries (France, Germany, Italy, 
Netherlands, Spain, United Kingdom) with possible extension to other countries. 
8
SELECTION AND WITHDRAWAL OF PATIENTS
8.1
Selection criteria
Before any data are collected for any patient in this NIS, written data consent will be properly 
executed and documented.
The following selection criteria must be followed for patients entering the NIS:
1. Patient has never been treated with LCM prior to this NIS or treatment with LCM for the first 
time started no earlier than 7 days prior to enrollment in this NIS.
2. The decision by the treating physician to prescribe LCM falls within current standard clinical 
practice, and the treatment decision is clearly separated from the decision to consider 
inclusion of the patient in the NIS.
3. A Patient Data Consent form is signed and dated by the patient and/or by the parent(s) or 
legal representative. 
4. Patient is a male or female ≥16 years of age.
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UCB
01 Jun 2015
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Page 13 of 35
5. Patient must have a diagnosis of BTRE secondary to low-grade glioma (World Health 
Organization Grade 1 to 2 at time of enrollment).
6. Patient has a retrospective Baseline seizure frequency of at least 1 partial-onset seizure in the 
8 weeks prior to start of LCM treatment.
7. Patient does not have a previous diagnosis of epilepsy before tumor onset.
8. Patient does not have brain metastases.
9. Patient has a Karnofsky performance status scale index ≥60%.
10. Patient is currently taking only 1 or 2 Baseline AEDs for epilepsy other than LCM.
11. Patient has received a maximum of 4 different lifetime AEDs ever before entering the NIS.
8.2
Withdrawal criteria
Patients are free to withdraw from the study at any time, without prejudice to their continued 
care.
Physicians are free to add or withdraw any medication or to withdraw the patient from the study 
at their own discretion. 
If a patient needs to increase the dose of the Baseline AEDs (1 or 2) or needs to be treated with 
more than 2 AEDs other than LCM, these changes can be implemented, but the patient will be 
withdrawn from the study.
If the physician elects to stop LCM treatment, the patient will be withdrawn from the study.
The primary reason for withdrawal must be documented in the patient's eDF. When the primary
reason for withdrawal is an ADR, the ADR must be reported as described in Section 10.1.7.
9
STUDY TREATMENT(S)
Patients will be treated with commercially available LCM and with commercially available 
AEDs, as prescribed by treating physicians, in accordance with current clinical practice.
9.1
Numbering of patients
Each patient will receive a unique 5-digit number assigned when entering the study that serves as 
the patient identifier throughout the study.
The patient identification list will be kept by the treating physician. Access to this list may be 
granted only to members of staff, authorized persons of UCB (or designees), and the competent 
authorities. The study monitor is also bound to confidentiality. After the end of the study, the 
identification list will remain with the physician.
10
ASSESSMENT OF SAFETY
For the assessment of safety of LCM, the causal relationship, seriousness, and outcome of ADRs 
and AESIs will be collected during the Observation Period. It is the task of the treating physician 
to make a judgment about a causal relationship with the LCM intake.
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01 Jun 2015
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Lacosamide
EP0045
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Page 14 of 35
10.1
Adverse events and adverse drug reactions
10.1.1
Definitions of adverse events and adverse drug reactions
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation 
patient administered a pharmaceutical product which 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 product, whether or not related to the medicinal product.
An ADR is a response to a medicinal product which is noxious and not intended. This includes 
adverse reactions which arise from:

The use of a medicinal product within the terms of the marketing authorization;

The use outside the terms of the marketing authorization, including overdose, off-label use, 
misuse, abuse, and medication errors; and

Occupational exposure (this refers to the exposure to a medicinal product as a result of one’s 
professional or nonprofessional occupation)
10.1.2
Reporting and description of adverse events
In order to ensure complete safety data collection, all ADRs and AESIs (Section 10.1.8) 
occurring during the study (ie, after signing the Patient Data Consent form or after first 
administration of the study drug, whatever comes first) must be reported. This includes all ADRs 
and AESIs not present prior to the initial visit and all ADRs and AESIs that recurred or worsened 
after the initial visit (eg, underlying or previous concomitant disease).
Signs or symptoms of the condition/disease for which the study treatment is being studied should 
be recorded as ADRs or AESIs 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 treating physician from the patient’s history or the Baseline Period.
When recording an ADR or AESI, the treating physician should use the overall diagnosis or 
syndrome using standard medical terminology, rather than recording individual symptoms or 
signs. The Adverse Event Report form and source documents should be consistent. 
Details for completion of the Adverse Event Report form are described in the AE reporting 
instructions.
10.1.3
Follow up on adverse events
An ADR or AESI should be followed until it has resolved, has a stable sequelae, the treating 
physician determines that it is no longer clinically significant, or the patient is lost to follow up. 
If an ADR or AESI is still ongoing at the end of the study for a patient, follow up might be 
requested by local UCB’s Drug Safety department, depending on the nature of the ADR/AESI. 
Follow up should be provided until resolution/stable level of sequelae, the treating physician no 
longer deems that it is clinically significant, or until the patient is lost to follow up (ie, cannot be 
contacted). If no follow up is provided, the treating physician must provide a justification.
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01 Jun 2015
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Lacosamide
EP0045
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Page 15 of 35
10.1.4
Pregnancy
If a treating physician is notified that a patient has become pregnant after the first intake of LCM, 
the treating physician must notify UCB’s local Drug Safety department immediately (a 
Pregnancy Report and Outcome form will be provided to the treating physician for completion). 
The treating physician shall inform the patient of the information currently known about 
potential risks and about available treatment alternatives. 
The pregnancy and the outcome (birth, miscarriage, abortion) will be documented on the 
Pregnancy Report and Outcome form provided to the treating physician. 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 treating physician has to report on the health of the mother and 
of the child. Every reasonable attempt should be made to follow the development and health of 
the child for at least 30 days after birth for any significant medical issues or developmental 
delay.
If the patient is lost to follow up and/or refuses to give information, written documentation of 
attempts to contact the patient needs to be provided by the treating physician and filed at the site. 
UCB’s local Drug Safety department is the primary contact for any questions related to the data 
collection for the pregnancy, birth, and follow up.
In cases where the partner of a male patient enrolled in a NIS becomes pregnant, the treating 
physician or designee is asked to contact the patient to request consent via the Partner Pregnancy 
Consent form. In case of questions about the consent process, the treating physician may contact 
UCB’s local Drug Safety department. The treating physician will complete the Pregnancy Report 
and Outcome form and send it to UCB’s local Drug Safety department only after the partner has 
agreed that additional information can be captured and has provided the signed Partner 
Pregnancy Consent form. UCB’s local Drug Safety department is also the primary contact for 
any questions related to the data collection for the partner pregnancy, eventual birth, and follow 
up.
10.1.5
Overdose of lacosamide
Excessive dosing (beyond the maximal allowed dose according to marketing authorization) 
should be reported on the Adverse Event Report form, whether the overdose is associated with 
an ADR/AESI or not. Any ADR associated with excessive dosing must be followed as any other 
ADR would be followed.
10.1.6
Safety signal detection
Reported ADRs or AESIs from this study will be reviewed periodically together with other 
safety information received at UCB, to detect as early as possible any safety concern(s) related to 
the treatment so that treating physicians, clinical study patients, and regulatory authorities will be 
informed appropriately and as early as possible.
10.1.7
Procedures for reporting adverse events and adverse drug reactions
The patient 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)?”
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Page 16 of 35
Following a causality assessment, the physician will document all spontaneously reported ADRs 
by the patient in the Adverse Event Report form. In addition, the treating physician should 
review any self-assessment procedures employed.
If an ADR or AESI is reported, UCB’s local Drug Safety department must be informed within 
1 working day of receipt of this information by the site (see contact details for safety reporting  
on the Study Contact Information page of this NIS observational plan). The treating physician 
must forward to UCB (or its representative) a duly completed Adverse Event 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.
If clarifications on the ADR or AESI are necessary, UCB shall request additional information 
from the treating physician.
The Adverse Event Report form and other requested information must be provided in English.
Additional information (eg, autopsy or laboratory reports) received by the treating physician 
must be provided within 24 hours. All documents in the local language must be accompanied by 
a translation in English, or the relevant information included in the same document must be 
summarized in the Adverse Event Report form.
The treating physician is specifically requested to collect and report to UCB (or its 
representative) any ADRs or AESIs (Section 10.1.8), and to also inform participating patients of 
the need to inform the treating physician of any AE during the study.
At the conclusion of the study, ADR or AESI data will be extracted from the global safety 
database and will be analyzed along with the clinical data to allow for the final summary of the 
safety variables (see Section 11.3.4). The current Summary of Product Characteristics for LCM
should be considered for the evaluation of ADR expectedness.
10.1.8
Adverse events of special interest
An AESI is any AE that a regulatory authority has mandated to 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 the LCM AESIs:

The following arrhythmias: atrial fibrillation/flutter, ventricular tachycardia or fibrillation, 
atrioventricular block (second degree, Type I and II, and third degree), and marked 
bradycardia (<45 beats/min)

Syncope or loss of consciousness (other than seizure related)

Serious suspected multiorgan hypersensitivity reactions
Serious suspected multiorgan hypersensitivity cases may be identified and reported to the 
sponsor by the treating physician using the following algorithm as agreed with the US Food 
and Drug Administration:

An AE or laboratory value (as defined in the following text) suggestive of internal organ 
involvement (including but not limited to hepatitis, nephritis, pneumonitis, carditis, 
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EP0045
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Page 17 of 35
colitis, encephalitis, pancreatitis, myositis, arthritis, or hematologic system involvement) 
combined with at least 1 of the following: fever, rash, lymphadenopathy, or eosinophilia.

Treatment-emergent abnormal laboratory value criteria suggestive of internal organ 
involvement or eosinophilia:
◦
Eosinophils % ≥10%
◦
Eosinophils absolute ≥0.5G/L
◦
Neutrophils absolute <1.5G/L
◦
Platelets ≤100G/L
◦
Alanine aminotransferase ≥2x upper level of normal (ULN)
◦
Aspartate aminotransferase ≥2xULN
11
STATISTICS
A description of statistical methods is presented below and will be described in more detail in the 
Statistical Analysis Plan.
11.1
Definition of analysis sets
For this NIS, the following definitions will apply:
The Enrolled Set (ES) is defined as all patients included in the study and for whom at least 
Visit 1 is documented. The ES will be used for patient disposition and patient data listings only.
The Safety Set (SS) is defined as all patients included in this study receiving treatment with 
LCM at least once in the study. The SS will be used for the analysis of the retention and 
discontinuation rates, time to discontinuation, safety data, and Baseline characteristics of the 
patients.
The Full Analysis Set (FAS) is defined as all patients in the SS who have at least 1 post-Baseline 
PGIC or seizure assessment. The FAS will be used for the analysis of the primary and most 
secondary variables.
The modified FAS is defined as all patients in the FAS ≥16 years of age and treated with daily 
LCM doses ≤400mg, representing the on-label use of LCM.
11.2
General statistical considerations
All variables will be summarized using descriptive statistics; there will be no inferential 
analyses. For continuous variables, summary statistics (number of available observations, mean, 
standard deviation, minimum, median, and maximum) will be tabulated. Categorical variables 
will be summarized by the number of patients and the percent of patients in each category. For 
time to event variables, medians derived using Kaplan-Meier estimates and corresponding 
95% confidence intervals (CIs) will be presented.
Data from patients who prematurely withdraw from the study will be analyzed up to the final 
visit attended.
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Lacosamide
EP0045
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Page 18 of 35
11.3
Planned analyses
11.3.1
Analysis of the primary variable
The number and percentage of responders, where a responder is a patient experiencing a 50% or 
greater reduction in partial-onset seizure frequency from Visit 1 (Baseline) to Visit 3 (Month 6 or 
end of Observation Period), will be presented for the FAS.
The number and percentage of patients with each PGIC value will be summarized at Visit 3 
(Month 6 or end of the Observation Period) for the FAS. The number and percentage of patients 
who improved (scores 1 to 3), had no change (score 4), and worsened (scores 5 to 7) will also be 
provided.  
11.3.2
Analysis of secondary variables
Secondary variables will be analyzed using descriptive statistics. The analysis set used for each 
variable will be defined in the SAP.
Retention rate will be summarized using descriptive statistics based on the number and 
percentage of patients remaining in the study and on LCM treatment for 6 months (6-month 
retention rate). A 2-sided 95% CI for the 6-month retention rate will be presented.
Time to discontinuation of LCM from the date of first dose of LCM will be analyzed using 
Kaplan-Meier methods. The median time to discontinuation (days) of LCM including 
corresponding 2-sided 95% CIs for the median time to discontinuation will be calculated. 
Patients who complete the 6-month Observation Period will be censored on the date of the final
LCM administration or the study termination date if the date of the final LCM administration is 
not available.
Descriptive statistics for the observed value and change from Visit 1 (Baseline) to Visit 3 (Month 
6 or end of Observation Period) in the EQ-5D-5L VAS score and utility as converted from the 
5 dimensions will be presented. The EQ-5D-5L will be assessed only for patients with an 
evaluable Baseline assessment (eg, patients who have not started LCM at the time of the Visit 1 
assessment).
Descriptive statistics for the observed value and change from Visit 1 (Baseline) to Visit 3 (Month 
6 or end of Observation Period) in the MDASI-BT will be presented. The MDASI-BT will be 
assessed only for patients with an evaluable Baseline assessment (eg, patients who have not 
started LCM at the time of the Visit 1 assessment). 
Descriptive statistics for percent change in seizure frequency per 28 days from Visit 1 (Baseline)
to Visit 3 (Month 6 or end of Observation Period) will be presented. Median percentage of 
seizure change from Baseline to Visit 3 (Month 6 or end of Observation Period) will be 
presented.
The number and percentage of patients achieving a seizure-free status (Yes/No) at the end of the 
6-month Observation Period will be presented.
The number and percentage of patients who discontinue LCM due to an ADR and due to lack of 
effectiveness will be presented separately. 
The number and percentage of patients with each CGIC value will be summarized at Visit 3 
(Month 6 or end of the Observation Period). The number and percentage of patients who 
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
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Page 19 of 35
improved (scores 1 to 3), had no change (score 4), and worsened (scores 5 to 7) will also be 
provided. 
11.3.3
Subgroup analyses
Subgroup analyses of the more relevant variables will be performed. Details of these analyses 
will be described in the Statistical Analysis Plan.
11.3.4
Analysis of safety variables
Adverse drug reactions will be coded for analysis with the latest version of the Medical 
Dictionary for Regulatory Activities (MedDRA®).
Adverse drug reactions that occur during this study will be presented by MedDRA system organ 
class (SOC) and preferred term (PT) in a frequency table giving the number of events, the 
number of patients who experience the event, and the percentage of patients who experience the 
event. Patients with multiple ADRs will be counted only once within each PT and SOC for the 
number of patients and the percentage of patients who experience an event. 
Serious ADRs that occur during the study will be presented by MedDRA SOC and PT in a 
frequency table giving the number of events, the number of patients who experience the event, 
and the percentage of patients who experience the event. Patients with multiple serious ADRs 
will be counted only once within each PT and SOC.
Adverse drug reactions leading to withdrawal that occur during the study will be presented by 
MedDRA SOC and PT in a frequency table giving the number of events, the number of patients 
who experience the event, and the percentage of patients who experience the event. Patients with 
multiple ADRs leading to withdrawal will be counted only once within each PT and SOC.
A listing of all ADRs will be provided. An overall summary table of all ADRs will be presented
as follows:

Individual patients (identified by patient numbers) experiencing a given ADR grouped by 
SOC, High Level Term (HLT), PT, and severity.

A glossary of all physician-reported terms, grouped by coded SOC, HLT, and PT. This table 
will serve as a glossary of PTs, showing which reported terms are summarized under each 
PT.
All table summaries will be sorted alphabetically by SOC and by decreasing relative frequency 
of each PT within SOC.
11.4
Planned interim analysis and data monitoring
No interim analysis or data monitoring board is planned in this NIS. Selected interim data may 
be reviewed periodically to detect as early as possible any safety concern(s) related to LCM and 
appropriately inform the treating physicians, patients, regulatory authorities, and/or 
Investigational Review Boards/Independent Ethics Committees.
11.5
Determination of sample size
A sample size of 100 enrolled patients to obtain 93 evaluable patients was chosen for this study 
based on an expected 6-month responder rate (where a responder is a patient experiencing a 50% 
or greater reduction in partial onset seizure frequency from Visit 1 [Baseline] to Visit 3 [Month 6 
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 20 of 35
or end of Observation Period]) of 60% with an expected precision in the 95% CI of 
approximately ±10% for this estimate of response. 
When the sample size is 93, a 2-sided 95% CI for a single proportion using the large sample 
normal approximation will extend 0.10 from the observed proportion for an expected proportion 
of 0.60.
Recruitment will be stopped at 100 enrolled patients and withdrawals will not be replaced.
12
STUDY MANAGEMENT AND ADMINISTRATION
12.1
Quality assurance
12.1.1
Monitoring
In order to safeguard and assure data quality, a site management plan will be developed that will 
include details on site monitoring visits, site management by telephone, and source data 
verification. 
Training on study procedures (eg, the handling of the eDF and the reporting of ADRs or AESIs)
will be provided during site initiation. Any medical and/or methodological questions arising 
during the study will be answered by UCB or designee.
12.1.2
Data handling
12.1.2.1
Case Report form completion
The study is performed using electronic data capture. The treating physician is responsible for 
prompt reporting of accurate, complete, and legible data in the eDFs and in all required reports.  
Any change or correction to the eDF after saving must be accompanied by a reason for the 
change. Corrections made after the treating physician’s review and approval (by means of a 
password/electronic signature) will be reapproved by the treating physician. The treating 
physician should maintain a list of personnel authorized to enter data into the eDF. Detailed 
instructions will be provided in the eDF Completion Guidelines.
12.1.2.2
Database entry and reconciliation
Case Report forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system. Computerized data cleaning checks will be 
used in addition to manual review to check for discrepancies and to ensure consistency of the 
data. The data are entered into the eDFs once and are subsequently verified. An electronic audit 
trail system will be maintained within the clinical data management system to track all data 
changes in the database once the data have been saved initially into the system or electronically 
loaded. Regular backups of the electronic data will be performed.
12.2
Termination of study
As soon as the planned number of 100 patients is included, no additional patients will be 
included in the study.
For the individual patient, this NIS will end with the documentation conducted during their final 
visit. Study participation can also be terminated by the patient at any time.
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 21 of 35
The sponsor reserves the right to terminate the study at an early stage and/or to close individual 
sites. Potential reasons for an early termination include:

An insufficient number of patients enrolled in the study

Upon the request of regulatory authorities

The participating physician does not adhere to the applicable rules, provisions, laws, and 
guidelines
12.3
Data archiving
Immediately after approval of the final report, the documentation forms will be archived for a 
minimum period of 10 years, including the ADR/AESI documentation and ADR/AESI
correspondence. The latter will be archived by the UCB Drug Safety department without any 
time constraints.
12.4
Legal provisions and ethics
12.4.1
Data protection and data privacy declaration
The legal provisions for data protection will be observed. Prior to inclusion, the patient will be 
given information in writing that describes the purpose and procedures of the study and explains 
the requirements of data protection. The patient has to agree in writing that his/her medical data 
will be used for the evaluation of the study results by signing a study-specific Patient Data 
Consent form.
Information relating to participating physicians will be declared, and the physicians will be 
informed, within the framework of their financial agreement, of their right to access, object to, 
and correct this information.
12.4.2
Report of the Ethics Committee
Prior to the implementation of this NIS, the treating physician will have written, signed, and 
dated full approval for the protocol from the appropriate national scientific and ethical bodies in 
accordance with any local regulations and laws.
12.4.3
Notification/submission to relevant Regulatory Authority(ies)
Prior to the implementation of this NIS, all regulatory aspects of the study will be fulfilled with 
regard to regulatory submissions/filings when required by local regulations for NIS.
12.4.4
Legally required reports
This NIS is not a clinical study because it only pursues the objective of documenting the standard 
practical procedures and/or the data associated with the treatment of patients suffering from 
epilepsy. 
In accordance with the currently valid and applicable rules and provisions, the study will be 
entered into the official online registry of clinical studies that is maintained by the US National 
Institute of Health (http://www.clinicaltrials.gov) and is accessible to the public at large. In 
accordance with the applicable national and local regulations, the study will also be registered in 
national clinical study registries and/or results databases as necessary.
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 22 of 35
13
REMUNERATION
Any payments to physicians will be in accordance with any local regulations and laws and will 
compensate only the additional work load related to the conduct of the study. The remuneration 
shall be regulated in a separate agreement to be concluded between UCB BIOSCIENCES GmbH 
and the participating physician and/or his or her clinic administration.
14
FINAL REPORT AND PUBLICATION
A final report will be prepared describing the results of the study. The results of the study are to 
be submitted to the study physicians, Ethic Committees, and Regulatory Authorities according to 
local regulations and laws.
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 23 of 35
15
RECOMMENDED SCHEDULE OF STUDY ASSESSMENTS
Table 15‒1: Recommended schedule of study assessments
Assessments
Visit 1a
(Baseline)
Visit 2
Approximately 3 months 
after Baseline according 
to routine practiceb
Visit 3
(End of Observation Period or 
Withdrawal Visitc)
Approximately 6 months after 
Baseline according to routine 
practiceb
Signed data consent
X
Demographic data
X
Medical history
Xd
Seizure history
Xd
Tumor diagnosis and grade (including review of most 
recent brain imaging results [CT or MRI])
X
X
Prior and concomitant tumor management (surgical 
procedures, chemotherapies, radiotherapy)
Xd
X
Prior and concomitant AEDs
X
X
X
Other prior and concomitant epilepsy treatment
X
X
X
Other prior and concomitant relevant medications
Xd
X
X
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X
Documentation of LCM administration
X
X
X
Documentation of seizure information (including 
seizure frequency and type)e
X
X
Karnofsky performance status 
X
X
X
EQ-5D-5L
X
X
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 24 of 35
Table 15‒1: Recommended schedule of study assessments
Assessments
Visit 1a
(Baseline)
Visit 2
Approximately 3 months 
after Baseline according 
to routine practiceb
Visit 3
(End of Observation Period or 
Withdrawal Visitc)
Approximately 6 months after 
Baseline according to routine 
practiceb
MDASI-BT
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X
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Withdrawal criteria
X
X
ADR=adverse drug reactions; AED=antiepileptic drug; AESI=adverse event of special interest; CGIC=Clinical Global Impression of Change; CT=computerized 
tomography; EQ-5D-5L=5-Level EuroQol-5 Dimension Quality of Life Assessment; LCM=lacosamide; MRI=magnetic resonance imaging; MDASI-BT=M.D. 
Anderson Symptom Inventory - Brain Tumor; PGIC=Patient Global Impression of Change
a Visit 1 will be performed after the decision is taken to start adjunctive LCM therapy. Treatment with LCM should be initiated according to routine clinical 
practice. If the first dose of LCM is given on the same day as Visit 1, it should be administered after Baseline assessments are complete. Previous treatment 
with LCM is allowed for up to 7 days prior to enrollment.
b The frequency of visits after Visit 1 will be based on local clinical practice and the patients’ requirements. The clinical procedures performed at each visit will 
also follow local clinical practice. It is estimated that patients will be followed at least every 3 months. 
c Patients who discontinue early should perform Visit 3 assessments as a Withdrawal Visit.
d During the previous 8 weeks and relevant information in the past according to the physician’s decision.
e The treating physician will evaluate at each visit, as part of standard practice with the patient, the frequency and type of seizures experienced by the patient 
since the previous study visit.
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 25 of 35
16
REFERENCES
Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC, et al. Practice 
parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. 
Neurology. 2000;54:1886-93.  
Hildebrand J, Lecaille C, Perennes J, Delattre JY. Epileptic seizures during follow-up of patients 
treated for primary brain tumors. Neurology. 2005;65:212-5.
Maschio M. Brain tumor-related epilepsy. Curr Neuropharmacol. 2012;10:124-33.
Maschio M, Dinapoli L, Mingoia M, Sperati F, Pace A, Pompili A, et al. Lacosamide as add-on 
in brain tumor-related epilepsy: preliminary report on efficacy and tolerability. J Neurol. 
2011;258:2100-4. 
Noack-Rink M, Mayer T, Arnold S, Kumke T, Runge U. Lacosamide as add-on to monotherapy 
in patients with partial-onset seizures: Interim results of the post-marketing VITOBA study 
(VImpaT Added to One Baseline AED). American Academy of Neurology (AAN) 2012 Annual 
Meeting. P06.126.
Rossetti AO, Stupp R. Epilepsy in brain tumor patients. Curr Opin Neurol. 2010;23:603-9.
Saria MG, Corle C, Hu J, Rudnick JD, Phuphanich S, Mrugala MM, et al. Retrospective analysis 
of the tolerability and activity of lacosamide in patients with brain tumors. J Neurosurg. 
2013;118:1183-7.
Singh G, Rees JH, Sander JW. Seizures and epilepsy in oncological practice: causes, course, 
mechanisms and treatment. J Neurol Neurosurg Psychiatry. 2007; 78:342-9.
Stephen LJ, Kelly K, Parker P, Brodie MJ. Adjunctive lacosamide in clinical practice: sodium 
blockade with a difference? Epilepsy Behav. 2011;22:499-504.
UCB. Vimpat. In: ® (lacosamide), ed. summary of product characteristics. EU: Belgium; 2011.
Vecht CJ, Wilms EB. Seizures in low- and high-grade gliomas: current management and future 
outlook. Expert Rev Anticancer Ther. 2010;10:663-9.
Villanueva V, López-Gomáriz E, López-Trigo J, Palau J, García M, Villarroya T, et al. Rational 
polytherapy with lacosamide in clinical practice: results of a Spanish cohort analysis 
RELACOVA. Epilepsy Behav. 2012;23:298-304.
Vimpat: EPAR–Scientific Discussion report: EMA/222258/2012, EMEA/H/C/000863, 
17 Sep 2008. http://www.emea.europa.eu/docs/en_GB/document_library/EPAR_-
_Public_assessment_report/human/000863/WC500050341.pdf. Accessed 10 Apr 2014.
Wen PY, Marks PW. Medical management of patients with brain tumors. Curr Opin Oncol.
2002;14:299-307.  
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 26 of 35
17
APPENDICES
17.1
NIS Observational Plan Amendment 1
Rationale for the amendment
The main purpose of this substantial amendment is to amend the selection criteria in order to 
facilitate patient recruitment by the sites. Feedback from the study sites has confirmed that the 
current selection criteria are too restrictive and are consequently impeding access to suitable 
patients who could be eligible for study entry whilst undergoing routine care. This 
noninterventional study will add valuable data concerning the effectiveness of LCM within 
routine clinical practice when added to an existing treatment regime of 1 or 2 Baseline AEDs in 
patients with BTRE. 
Modifications and changes
Global changes
The following changes were made throughout the NIS observational plan:

The study title was amended as patients can receive more than 1 (either 1 or 2) Baseline 
AEDs.

Section 1 Rationale for the study, Section 3 Study objectives, Section 5 Study design, 
Section 8.1 Selection criteria and Section 8.2 Withdrawal criteria were amended so patients 
can receive either 1 or 2 Baseline AEDs.

The number of specialized centers was increased to approximately 25 centers.

Selection Criterion 1 was amended to include patients who had never previously received 
LCM and those who had received LCM within 7 days prior to enrollment in the study. 

Selection Criteria 2 and 6 were amended as patients can be on LCM prior to enrollment in 
the study. 

Selection Criterion 5 was amended as the number of Baseline AEDs taken for epilepsy was 
increased from 1 to either 1 or 2.

Selection Criterion 10 was amended to increase the number of Baseline AEDs taken for 
epilepsy from 1 to either 1 or 2. 

Selection Criterion 11 was amended to allow a lifetime maximum of 4 different AEDs.

Selection Criterion 12 was removed as this criterion was covered by Selection Criterion 2.

Administrative changes: minor changes were made to study contact information; the section 
Declarations and signatures of persons responsible for the study was updated for electronic 
signature; minor edits were made to the Pregnancy section.
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 27 of 35
Specific changes
This section displays the modifications in this amendment compared with the final 
noninterventional observational plan dated 23 Jun 2014. The changes are displayed in the order 
of appearance.
Change #1
Title page, Study title 
A NONINTERVENTIONAL STUDY OF VIMPAT® (LACOSAMIDE) ADDED TO ONE 
BASELINE ANTIEPILEPTIC DRUG THERAPY IN PATIENTS WITH BRAIN 
TUMOR-RELATED EPILEPSY (VIBES)
Has been changed to:
A NONINTERVENTIONAL STUDY OF VIMPAT® (LACOSAMIDE) AS ADJUNCTIVE
ANTIEPILEPTIC DRUG THERAPY IN PATIENTS WITH BRAIN TUMOR-RELATED 
EPILEPSY (VIBES)
Change #2
STUDY CONTACT INFORMATION
Study Physician
Name:
, MD
Address:
UCB Pharma S.A.
Allée de la Recherche 60
1070 Brussels
BELGIUM
Phone:
Fax:
Email:
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 28 of 35
Has been changed to:
Study Physician
Name:
, MD
Address:
UCB Pharma S.A.
Allée de la Recherche 60
1070 Brussels
BELGIUM
Phone:
Fax:
Email:
Clinical Trial Biostatistician
Name:
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Email:
Has been changed to:
Clinical Trial Biostatistician
Name:
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Phone:
Fax:
Email:
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 29 of 35
Clinical Monitoring Contract Research Organization
Name:
PRA
Address:
Gottlieb-Daimler-Strasse 10
68165 Mannheim
GERMANY
Phone:
+49 621 8782 872
Fax:
+49 621 8782 184
Has been changed to:
Clinical Monitoring Contract Research Organization
Name:
PRA GmbH 
Address:
Gottlieb-Daimler-Strasse 10
68165 Mannheim
GERMANY
Phone:
+49 621 8782 0
Fax:
+49 621 8782 184
Change #3
Declarations and signatures of persons responsible for the study
I confirm that I have carefully read and understand this noninterventional study observational 
plan and agree to conduct this noninterventional study as outlined.
Clinical Project Manager
_____________________________
Date/Signature
Clinical Trial Biostatistician
_____________________________
Date/Signature
Study Physician
, MD
_____________________________
Date/Signature
Lead Clinical Development Representative
_____________________________
Date/Signature
Medical Affairs Medical Director
_____________________________
Date/Signature
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 30 of 35
Has been revised and moved to Section 18:
Declarations and signatures of persons responsible for the study
I confirm that I have carefully read and understand this noninterventional study observational 
plan and agree to conduct this noninterventional study as outlined.
Change #4
Section 1 RATIONALE FOR THE STUDY, paragraphs 3, 10, and 11
Lacosamide (LCM, VIMPAT®) is an antiepileptic drug (AED), which has been shown to provide 
a favorable benefit-risk profile and was approved by the European Medicine Agency (EMA) on 
29 Aug 2008 (EU/1/08/470/01 to 013 and EU/1/08/470/016 to 023; EMA reference 
EMEA/H/C/000863) as adjunctive therapy in the treatment of partial-onset seizures with or 
without secondary generalization in patients with epilepsy aged 16 years and older (film-coated 
tablets of 50mg, 100mg, 150mg, and 200mg, syrup of 10mg/mL, and solution for infusion of 
10mg/mL). In addition, LCM is approved as adjunctive therapy in the treatment of partial-onset 
seizures in adults with epilepsy in the United States and in other regions.
EP0045 is a multicenter, prospective NIS conducted at specialized sites in approximately 
6 European countries, with a 6-month Observation Period. Lacosamide will be added to any 
AED monotherapy in approximately 100 patients with BTRE.
The primary objective of this study is to evaluate in routine clinical practice the effectiveness of 
LCM added to a single AED in the treatment of patients with BTRE due to low-grade glioma. 
The secondary objective of this study is to evaluate the tolerability and quality of life (QoL) of 
patients with BTRE due to low-grade primary brain tumor who are treated with LCM added to a 
single AED.
Have been changed to:
Lacosamide (LCM, VIMPAT®) is an antiepileptic drug (AED), which has been shown to provide 
a favorable benefit-risk profile and was approved by the European Medicine Agency (EMA) on 
29 Aug 2008 (EU/1/08/470/01 to 013 and EU/1/08/470/016 to 023; EMA reference 
EMEA/H/C/000863) as adjunctive therapy in the treatment of partial-onset seizures with or 
without secondary generalization in patients with epilepsy aged 16 years and older (film-coated 
tablets of 50mg, 100mg, 150mg, and 200mg, syrup of 10mg/mL, and solution for infusion of 
10mg/mL). In addition to the European Union, LCM is approved as adjunctive therapy in adults 
suffering from partial-onset seizures in at least 38 other countries to date. In the United States, 
LCM is approved as adjunctive therapy or monotherapy in patients age 17 years and older and 
suffering from partial-onset seizures.
EP0045 is a multicenter, prospective NIS conducted at specialized sites in approximately 
6 European countries, with a 6-month Observation Period. Lacosamide will be added to any 
AED therapy (1 or 2 AEDs) in approximately 100 patients with BTRE.
The primary objective of this study is to evaluate in routine clinical practice the effectiveness of 
LCM added to 1 or 2 AEDs in the treatment of patients with BTRE due to low-grade glioma. 
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 31 of 35
The secondary objective of this study is to evaluate the tolerability and quality of life (QoL) of 
patients with BTRE due to low-grade primary brain tumor who are treated with LCM added to 
1 or 2 AEDs.
Change #5
Section 3 STUDY OBJECTIVES
The primary objective of this study is to evaluate the effectiveness and patient global impression 
of LCM added to a single AED in the treatment of patients with BTRE due to low-grade primary 
brain tumor. 
The secondary objective of this study is to evaluate the tolerability and QoL of patients with 
BTRE due to low grade primary brain tumor who are treated with LCM added to a single AED.
Has been changed to:
The primary objective of this study is to evaluate the effectiveness and patient global impression 
of LCM added to 1 or 2 AEDs in the treatment of patients with BTRE due to low-grade primary 
brain tumor. 
The secondary objective of this study is to evaluate the tolerability and QoL of patients with 
BTRE due to low-grade primary brain tumor who are treated with LCM added to 1 or 2 AEDs.
Change #6
Section 5 STUDY DESIGN, paragraph 1
EP0045 is a multicenter, prospective, single-arm NIS conducted at specialized sites utilizing 
LCM added to AED monotherapy in patients ≥16 years of age with BTRE secondary to 
low-grade tumor. There are expected to be approximately 100 patients enrolled in the study (see 
Section 11.5).
Has been changed to:
EP0045 is a multicenter, prospective, single-arm NIS conducted at specialized sites utilizing 
LCM added to existing treatment with 1 or 2 Baseline AEDs in patients ≥16 years of age with 
BTRE secondary to low-grade tumor. There are expected to be approximately 100 patients 
enrolled in the study (see Section 11.5).
Change #7
Section 5 STUDY DESIGN, paragraph 5
The clinical evaluation of patients with BTRE secondary to low-grade tumor will be performed 
by the treating physician following routine clinical practice. All visits and assessments will be 
scheduled and conducted per routine clinical practice. It is anticipated that visits will occur every 
3 months based on standard of care; therefore, each patient will have approximately 3 visits 
during their participation in this study. These visits will consist of:
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 32 of 35

Visit 1, Baseline (to be performed before the first dose of LCM)

Visit 2, approximately 3 months after Baseline according to routine practice 

Visit 3, approximately 6 months after Baseline according to routine practice or end of 
Observation Period
Has been changed to:
The clinical evaluation of patients with BTRE secondary to low-grade tumor will be performed 
by the treating physician following routine clinical practice. All visits and assessments will be 
scheduled and conducted per routine clinical practice. It is anticipated that visits will occur every 
3 months based on standard of care; therefore, each patient will have approximately 3 visits 
during their participation in this study. These visits will consist of:

Visit 1, Baseline

Visit 2, approximately 3 months after Baseline according to routine practice 

Visit 3, approximately 6 months after Baseline according to routine practice or end of 
Observation Period
Change #8
Section 6 EXPECTED STUDY DURATION
The planned number of patients is 100 (see Section 11.5), with 93 evaluable patients expected.
Approximately 20 specialized centers are planned for participation. The expected recruitment
period is 12 months.
Has been changed to:
The planned number of patients is 100 (see Section 11.5), with 93 evaluable patients expected.
Approximately 25 specialized centers are planned for participation. The expected recruitment
period is 12 months.
Change #9
Section 8.1 Selection criteria
Selection Criterion 1
1. Patient has never been treated with LCM prior to this NIS.
Has been changed to:
1. Patient has never been treated with LCM prior to this NIS or treatment with LCM for the first 
time started no earlier than 7 days prior to enrollment in this NIS.
Selection Criterion 2
2. The decision by the treating physician to prescribe LCM for the first time falls within current
standard clinical practice, and the treatment decision is clearly separated from the decision to
consider inclusion of the patient in the NIS.
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 33 of 35
Has been changed to:
2. The decision by the treating physician to prescribe LCM falls within current standard clinical 
practice, and the treatment decision is clearly separated from the decision to consider 
inclusion of the patient in the NIS.
Selection Criterion 5
5. Patient must have a diagnosis of BTRE secondary to low-grade glioma (World Health 
Organization Grade 1 to 2 at time of enrollment), not sufficiently controlled by 1 Baseline 
AED.
Has been changed to:
5. Patient must have a diagnosis of BTRE secondary to low-grade glioma (World Health 
Organization Grade 1 to 2 at time of enrollment).
Selection Criterion 6
6. Patient has a retrospective Baseline seizure frequency of at least 1 partial-onset seizure in the 
8 weeks prior to Visit 1 (enrollment/Baseline visit).
Has been changed to:
6. Patient has a retrospective Baseline seizure frequency of at least 1 partial-onset seizure in the 
8 weeks prior to start of LCM treatment.
Selection Criterion 10
10. Patient is currently taking only 1 Baseline AED for epilepsy.
Has been changed to:
10. Patient is currently taking only 1 or 2 Baseline AEDs for epilepsy other than LCM.
Selection Criterion 11
11. Patient has received a maximum of 3 different lifetime AEDs ever before entering the NIS.
Has been changed to:
11. Patient has received a maximum of 4 different lifetime AEDs ever before entering the NIS.
Selection Criterion 12
The following selection criterion has been deleted:
12. Patient does not have contraindications according to the Summary of Product Characteristics 
for LCM.
Change #10
Section 8.2 Withdrawal criteria, paragraph 3
If a patient needs to increase the dose of the Baseline AED or needs to be treated with further 
AEDs, these changes can be implemented, but the patient will be withdrawn from the study.
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 34 of 35
Has been changed to:
If a patient needs to increase the dose of the Baseline AEDs (1 or 2) or needs to be treated with 
more than 2 AEDs other than LCM, these changes can be implemented, but the patient will be 
withdrawn from the study.
Change #11
Section 10.1.4 Pregnancy, final paragraph 
In cases where the partner of a male patient enrolled in a NIS becomes pregnant, the treating 
physician or designee is asked to contact the patient to request consent via the Partner Pregnancy 
Consent form that should be available in the treating physician’s site file. In case of questions 
about the consent process, the treating physician may contact UCB’s local Drug Safety 
department. The treating physician will complete the Pregnancy Report and Outcome form and 
send it to UCB’s local Drug Safety department only after the partner has agreed that additional 
information can be captured and has provided the signed Partner Pregnancy Consent form. 
UCB’s local Drug Safety department is also the primary contact for any questions related to the 
data collection for the partner pregnancy, eventual birth, and follow up.
Has been changed to:
In cases where the partner of a male patient enrolled in a NIS becomes pregnant, the treating 
physician or designee is asked to contact the patient to request consent via the Partner Pregnancy 
Consent form. In case of questions about the consent process, the treating physician may contact 
UCB’s local Drug Safety department. The treating physician will complete the Pregnancy Report 
and Outcome form and send it to UCB’s local Drug Safety department only after the partner has 
agreed that additional information can be captured and has provided the signed Partner 
Pregnancy Consent form. UCB’s local Drug Safety department is also the primary contact for 
any questions related to the data collection for the partner pregnancy, eventual birth, and follow 
up.
Change #12
Table 15‒1:
RECOMMENDED SCHEDULE OF STUDY ASSESSMENTS
Footnote a
a
Visit 1 will be performed before the first dose of LCM and after decision is taken to start 
adjunctive LCM therapy. Lacosamide can be administered on the same day of Visit 1 after 
Baseline assessments are complete.
Has been changed to:
a
Visit 1 will be performed after the decision is taken to start adjunctive LCM therapy. 
Treatment with LCM should be initiated according to routine clinical practice. If the first 
dose of LCM is given on the same day as Visit 1, it should be administered after Baseline 
assessments are complete. Previous treatment with LCM is allowed for up to 7 days prior to 
enrollment.
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UCB
01 Jun 2015
Noninterventional Study Observational Plan
Lacosamide
EP0045
Confidential
Page 35 of 35
18
DECLARATIONS AND SIGNATURES
Declarations and signatures of persons responsible for the study
I confirm that I have carefully read and understand this noninterventional study observational 
plan and agree to conduct this noninterventional study as outlined.
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