An Open Label, Multicenter, Safety and Pharmacokinetic Study of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
Phase: PHASE3
Conditions: Partial Epilepsy
Sponsor: SK Life Science, Inc.

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5 
June 20, 2019 
Page 1 of 135
SK Life Science Inc.
461 From Road 
Paramus, NJ 07652
An Open Label, Multicenter, Safety and Pharmacokinetic Study of YKP3089 
as Adjunctive Therapy in Subjects with Partial Onset Seizures
Clinical Study Protocol
May 21, 2015
Amendment 1, October 23, 2015
Amendment 2, April 14, 2016
Amendment 3, June 03, 2016
Amendment 4, July 28, 2017
Amendment 5, June 20, 2019

INVESTIGATOR SIGNATURE PAGE
Type of document:
Protocol
Protocol Amendment
Protocol title:
An 
Open 
Label, 
Multicenter, 
Safety 
and 
Pharmacokinetic Study of YKP3089 as Adjunctive 
Therapy in Subjects with Partial Onset Seizures
Original protocol date:
May 21, 2015
Amendment 1 Date
October 23, 2015
Amendment 2 Date
Amendment 3 Date 
Amendment 4 Date
Amendment 5 Date 
Protocol number:
April 14, 2016
June 03, 2016
July 28, 2017
June 20, 2019 
YKP3089C021
EudraCT number: 
2015-001859-67
By my signature, I confirm that my staff and I 
have carefully read and understand this protocol 
or protocol amendment, and agree to comply with 
the conduct and terms of the study specified 
herein and with any other study conduct 
procedures provided by SK Life Science Inc.
Investigator’s Signature
Date
______________________________
______________
Print Name
______________________________

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5 
June 20, 2019 
Page 5 of 135
PROTOCOL AMENDMENTS
Amendment 1
Reasons for amendment
1. To increase number of subjects to be enrolled in the study
2. To slow the rate of titration of YKP3089 in subjects taking AEDs other than phenytoin or 
phenobarbital
3. To allow enrollment of all three groups of subjects (phenytoin, phenobarbital and other 
concomitant AEDs) concurrently
4. To provide updated YKP3089 exposure, safety and efficacy data
5. To clarify felbamate exclusion requirements
6. To make administrative changes

Amendment 1 Summary of Changes
Section
Old Text
Amended Text
Rationale
1. PROTOCOL 
SYNOPSIS
Study Centers
Approximately 50 sites (multiple 
countries)
Approximately 75 sites (multiple countries)
To increase number 
of sites to account 
for increased 
number of subjects
1. PROTOCOL 
SYNOPSIS
Number of 
subjects
Initially at least 20 subjects taking 
phenytoin and at least 20 subjects taking 
phenobarbital; followed by an additional 
approximately 450 subjects taking AEDs 
other than phenytoin or phenobarbital, at a 
time to be determined by the Sponsor, to 
further evaluate long term safety.
At least 20 subjects taking phenytoin and at least 20 subjects 
taking phenobarbital and approximately an additional 700 subjects 
taking AEDs other than phenytoin or phenobarbital, to further 
evaluate long term safety.
To increase number 
of  subjects to be 
enrolled in the study
1. PROTOCOL 
SYNOPSIS
Design and 
methodology
Subjects on concomitant AEDs other than 
phenytoin or phenobarbital:
The titration phase for subjects on stable 
doses of other concomitant AEDs will be 4
weeks. Increasing doses of YKP3089 will 
be administered (50, 100, 150 and 
200mg/day) at 1-week intervals. The 
investigator may add, remove, or adjust 
the dosage of concomitant AEDs, as 
clinically indicated in this group of 
subjects. Monotherapy with YKP3089 will 
not be allowed.
Subjects on concomitant AEDs other than phenytoin or 
phenobarbital:
The titration phase for subjects on stable doses of other concomitant 
AEDs will be 8 weeks. Increasing doses of YKP3089 will be 
administered (50, 100, 150 and 200mg/day) at 2-week intervals. The 
investigator may add, remove, or adjust the dosage of concomitant 
AEDs, as clinically indicated in this group of subjects. Monotherapy 
with YKP3089 will not be allowed.
A recent  aggregate 
analysis revealed 
that the rate of 
rash/hypersensitivity 
reactions was lowest 
when the rate of 
titration was at 
50mg every two 
weeks
1. PROTOCOL 
SYNOPSIS
Statistics and 
analyses
The results of the open-label extension will 
be reported using summary tables, figures, 
and data listings. Summaries will be 
presented for demographic information and 
safety information only.
The results of the open-label extension will be reported using 
summary tables, figures, and data listings. Summaries will be 
presented for demographic information and safety information only.
To correct 
typographical error
3. STUDY 
ASSESSMENTS
Table 1
Colum 
headers 
were 
separate 
for 
phenytoin/phenobarbital 
vs 
other 
concomitant AEDs
All subjects have same titration rate with a single set of headers
All subjects will 
have the same 
titration rate
4.4.3
Clinical 
Safety and 
Efficacy
Cumulatively, approximately 800 subjects 
have been exposed to YKP3089 in a total of 
12 Phase 1 and 3 Phase 2 clinical studies. 
Cumulatively, 953 subjects have been exposed to YKP3089 in a 
total of 14 Phase 1 and 3 Phase 2 clinical studies. 
To provide updated 
exposure, safety and 
efficacy data

Amendment 2
Reasons for Amendment
1. To increase number of subjects to be enrolled in the study
2. To reduce the initial dose of YKP3089
3. To slow the rate of titration of YKP3089 
4. To update the exclusion criteria
5. To provide updated YKP3089 exposure, safety and efficacy data in the introduction
6. To increase the frequency of visits and evaluations during the first 16 weeks of therapy with YKP3089
7. To update the skin/hypersensitivity safety assessments
8. To provide information for two new dosage strengths
9. To update the risk benefit profile in the introduction
10. To make administrative changes

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5 
June 20, 2019 
Page 17 of 135
Amendment 2 Summary of Changes
Section
Old Text
Amended Text
Rationale
1. 
PROTOCOL 
SYNOPSIS
Study 
Center(s)
Approximately 75 sites (multiple countries)
Approximately 50-100  sites (multiple countries)
To increase 
number of 
sites to 
account for 
increased 
number of 
subjects
1. 
PROTOCOL 
SYNOPSIS
Number of 
subjects
At least 20 subjects taking phenytoin and at least 20 
subjects taking phenobarbital and approximately an 
additional 700 subjects taking AEDs other than 
phenytoin or phenobarbital, to further evaluate long 
term safety.
At least 20 subjects taking phenytoin and at least 20 subjects taking 
phenobarbital. Additional subjects taking AEDs other than phenytoin 
or phenobarbital, will be enrolled in order to expose a total of at least 
1,000 subjects for at least 6 months.
To increase 
number of 
subjects to be 
enrolled in 
the study
1. 
PROTOCOL 
SYNOPSIS
Design and 
methodology
The study will consist of a screening period, open-
label titration phase, open label maintenance phase 
and a taper and follow up.
Screening period
The screening period for subjects on stable doses of 
phenytoin or stable doses of phenobarbital or stable 
doses of other concomitant AEDs will be up to 21 
days. 
Titration phase 
Subjects on phenytoin or phenobarbital:
The titration phase for subjects on stable doses of 
phenytoin or stable doses of phenobarbital will be 8 
weeks. Increasing doses of YKP3089 will be 
administered (50, 100, 150 and 200mg/day) at 2-week 
intervals. 
Sparse 
sampling 
of 
phenytoin, 
phenobarbital and YKP3089 plasma levels will be 
The study will consist of a screening period, a 12 week open-label 
titration phase, an open label maintenance phase and a taper and follow 
up.  Clinic visits during the first 16 weeks of therapy will be every two 
weeks with a telephone contact between each visit.  At each visit during 
the first 16 weeks physical exams to evaluate signs of hypersensitivity 
will be performed and laboratory evaluations will be obtained. 
Screening period
The screening period for subjects on stable doses of phenytoin or stable 
doses of phenobarbital or stable doses of other concomitant AEDs will 
be up to 21 days. 
Titration phase 
Subjects on phenytoin or phenobarbital:
The titration phase for subjects on stable doses of phenytoin or stable 
doses of phenobarbital will be 12 weeks. Increasing doses of YKP3089 
will be administered (12.5, 25, 50, 100, 150 and 200mg/day) at 2-week 
intervals. Sparse sampling of phenytoin, phenobarbital and YKP3089 
To reduce the 
rate of 
DRESS 
incidence by 
lowering 
initial dose of 
YKP3089
and slowing 
the rate of 
titration

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5 
June 20, 2019 
Page 39 of 135
Amendment 3
Reasons for Amendment 
1. To allow subjects to increase the target dose up to 400 mg/day
2. Minor administrative changes 

Amendment 3 Summary of Changes
Section
Old Text
Amended Text
Rationale
1. PROTOCOL 
SYNOPSIS
Open Label 
Maintenance Phase
Subjects on phenytoin 
or phenobarbital
If the investigator feels that a subject 
requires a dose that is lower than 200 
mg/day, the dose can be reduced to a 
minimum of 50 mg/day once the target 
dose of 200 mg/day was reached. The 
dose adjustments may occur in weekly 
increments of 100-mg/day or 50-mg/day. 
However, the rate of change may be more 
rapid or slow as clinically indicated. The 
investigator may add, remove, or adjust 
the dosage of concomitant AEDs, as 
clinically indicated. Monotherapy with 
YKP3089 will not be allowed.
If the investigator feels that a subject requires a dose that is higher 
than 200 mg/day, the dose can be increased to a maximum of 400 
mg/day once the target dose of 200 mg/day was reached The 
upward dose adjustments should occur every other week in
increments of 50-mg/day. If the investigator feels that a subject 
requires a dose that is lower than 200 mg/day, the dose can be 
reduced to a minimum of 50 mg/day once the target dose of 200 
mg/day was reached. The downward dose adjustments may occur 
weekly by 100-mg/day or 50-mg/day. However, the downward 
rate of change may be more rapid or slow as clinically indicated. 
The investigator may add, remove, or adjust the dosage of 
concomitant AEDs, as clinically indicated. Monotherapy with 
YKP3089 will not be allowed.
To increase to a 
maximum of 
400mg/day
PROTOCOL 
SYNOPSIS
Open Label 
Maintenance Phase
Subjects on 
concomitant AEDs 
other than phenytoin  
or phenobarbital
If the investigator feels that a subject 
requires a dose that is lower than 200 
mg/day, the dose can be reduced to a 
minimum of 50 mg/day once the target 
dose of 200 mg/day was reached. The 
dose adjustments may occur in weekly 
increments of 100-mg/day or 50-mg/day. 
However, the rate of change may be more 
rapid or slow as clinically indicated.
For subjects taking other concomitant AEDs, the initial target 
dose will be 200 mg/day.  If the investigator feels that a subject 
requires a dose that is higher than 200 mg/day, the dose can be 
increased to a maximum of 400 mg/day once the target dose of 
200 mg/day was reached. The upward dose adjustments should 
occur every other week in increments of 50-mg/day. If the 
investigator feels that a subject requires a dose that is lower than 
200 mg/day, the dose can be reduced to a minimum of 50 mg/day 
once the target dose of 200 mg/day was reached. The downward 
dose adjustments may occur weekly by 100-mg/day or 50-
mg/day. However, the downward rate of change may be more 
rapid or slow as clinically indicated.
To increase to a 
maximum of 
400mg/day
Section 4.5 Rationale
Section 4.5.2.Dose 
Justification 
After reaching a target dose of 200mg, all subjects will be allowed 
to titrate up to a maximum dose of 400mg/day of YKP3089. A 
maximum dose of 400mg/day is justified by the additional efficacy  
To increase to a 
maximum of 
400mg/day

Amendment 4
Reasons for Amendment 
1. To update inclusion and exclusion criteria to more effectively screen patients for a safety study
2. To update Birth Control Methods Allowable for Enrollment of Subjects
3. To addvital signs details to the Study Assessment table
4. To update screening number assignment
5. To clarify prohibited medications or devices
6. To clarify pharmacokinetics sampling
7. To update Medical Monitor contact information
8. Minor administrative and editorial changes

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5 
June 20, 2019 
Page 43 of 135
Amendment 4 Summary of Changes
Section
Old Text
Amended Text
Rationale
3. STUDY 
ASSESSME
NTS
Table 1. 
Study 
Assessment 
Flow Chart
b. Vital signs include blood pressure, and heart rate (supine 
for 5 minutes).
b. Vital signs include blood pressure, heart rate (supine for 5 
minutes), temperature, and respiratory rate.
To update 
vital sign
details in the 
study 
assessment 
table 
3. STUDY 
ASSESSME
NTS
Table 1. 
Study 
Assessment 
Flow Chart
i. Two blood samples will be collected for the determination 
of YKP3089 plasma levels: the first one will be collected 
upon subjects’ arrival to the study unit; the second one 
should be collected within 2 to 4 hours after the first blood 
draw. Collect at visit 8 and/ or 9 depending on stability of 
dosing (doses must be stable for 2 weeks prior to these 
visits) of all concomitant AEDs including oxcarbazepine, 
topiramate, lamotrigine, lacosamide, clobazam, perampanel, 
levetiracetam, phenytoin and phenobarbital and YKP3089.
i. Two blood samples will be collected for the determination 
of YKP3089 plasma levels: For patients that are taking 
YKP3089 in the morning and coming into the visits in the 
morning, the first blood draw will be collected upon 
subjects’ arrival to the study unit; the second blood draw
should be collected within 30 minutes to 2 hours after the 
medication is taken. Collect at visit 8 and/ or 9 depending on 
stability of dosing (doses must be stable for 2 weeks prior to 
these visits) of all concomitant AEDs including 
oxcarbazepine, topiramate, lamotrigine, lacosamide, 
clobazam, perampanel, levetiracetam, phenytoin and 
phenobarbital and YKP3089.  YKP3089 PK draw is 
applicable for subjects on phenytoin and phenobarbital 
globally and all subjects at US sites.
To clarify 
pharmacokine
tics sampling
3. STUDY 
ASSESSME
NTS
Table 1. 
Study 
Assessment 
Flow Chart
j. At Visit 2, a single trough level of phenytoin or 
phenobarbital will be obtained. At visits 4, 5, 6, 7 and 8 two 
blood samples will be collected for the determination of 
phenobarbital and phenytoin plasma levels: the first one will 
be collected upon subjects’ arrival to the study unit; the 
second one should be collected within 2 to 4 hours after the 
first blood draw.
j. At Visit 2, a single trough level of phenytoin or 
phenobarbital will be obtained. At visits 4, 5, 6, 7 and 8 two 
blood samples will be collected for the determination of 
phenobarbital and phenytoin plasma levels: For subjects that
are taking phenytoin or phenobarbital in the morning and 
coming into the visits in the morning, the first blood draw
will be collected upon subjects’ arrival to the study unit; the 
second blood draw should be collected within 2 to 4 hours 
after the medication is taken.  
To clarify 
pharmacokine
tics sampling
3. STUDY 
ASSESSME
NTS
k. At Visit 2, a single trough level of concomitant AEDs will 
be obtained. At Visits 8 and 9, two blood samples will be 
collected for the determination of concomitant AED plasma 
k. Concomitant AED PK draw will be done at US sites only. 
At Visit 2, a single trough level of concomitant AEDs will 
be obtained. At Visits 8 and 9, two blood samples will be 
To clarify 
pharmacokine
tics sampling

Amendment 5
Reason for Amendment Change 
1. Version number and date updated - Version number and date updated throughout 
document.
2. SK Life Science Address update - SK Life Science, Inc. address updated from: 
SK Life Science, Inc., 22-10 Route 208 South Fair Lawn, NJ 07410 USA. To: SK 
Life Science, Inc., 461 From Road, 5th FL, Paramus, NJ 07652 USA

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5 
June 20, 2019 
Page 53 of 135
TABLE OF CONTENTS
TABLE OF CONTENTS ......................................................................................................53 
1 
PROTOCOL SYNOPSIS ..........................................................................................57 
2 
LIST OF ABBREVIATIONS ...................................................................................60 
3 
STUDY ASSESSMENTS ..........................................................................................62 
4 
BACKGROUND AND DOSE SELECTION ..........................................................66 
4.1 
Introduction..................................................................................................................66 
4.2 
Considerations for Studies of Epilepsy........................................................................66 
4.3 
Background..................................................................................................................67 
4.3.1 
YKP3089 Structure ................................................................................................67 
4.4 
Pharmacology ..............................................................................................................67 
4.4.1 
Absorption, Distribution, Metabolism, and Excretion...........................................67 
4.4.2 
Safety Pharmacology and Toxicity Studies............................................................69 
4.4.3 
Clinical Safety and Efficacy...................................................................................69 
4.5 
Rationale ......................................................................................................................74 
4.5.1 
Study Rationale......................................................................................................74 
4.5.2 
Dose Justification...................................................................................................75 
4.6 
Potential Risks and Benefits ........................................................................................76 
5 
STUDY OBJECTIVES ..............................................................................................77 
6 
STUDY DESIGN ........................................................................................................77 
6.1 
Overview......................................................................................................................77 
6.1.1 
Screening Period....................................................................................................77 
6.1.2 
Open label Treatment Period.................................................................................78 
6.1.2.1 
Titration Phase............................................................................................................78 
6.1.2.2 
Open Label Maintenance Phase..................................................................................80 
6.1.2.3 
Taper and follow up....................................................................................................83 
6.2 
Study Endpoints...........................................................................................................83 
6.2.1 
Pharmacokinetic Endpoints...................................................................................83 
6.2.2 
Safety Endpoints.....................................................................................................84 
7 
SELECTION OF STUDY POPULATION .............................................................84 
7.1 
Study Population and Sites ..........................................................................................84 

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5 
June 20, 2019 
Page 57 of 135
1
PROTOCOL SYNOPSIS
Name of 
company
SK Life Science Inc
Title of study
An Open Label, Multicenter, Safety and Pharmacokinetic Study of 
YKP3089 as Adjunctive Therapy in Subjects with Partial Onset Seizures
Protocol number 
YKP3089C021
Phase of 
development
Phase 3
Study duration
After 12 months of participation in the study, subjects will be evaluated for 
treatment response. Those who are benefiting from treatment with 
YKP3089 may continue use of the drug at the discretion of the investigator, 
until development is stopped by SK Life Science Inc or the product is 
approved for marketing, or anytime at the discretion of SK Life Science 
Inc.
Indication
Partial-onset epilepsy
Study center(s)
Approximately 80-110 sites (multiple countries)
Number of 
subjects
At least 20 subjects taking phenytoin and at least 20 subjects taking 
phenobarbital. Additional subjects taking AEDs other than phenytoin or 
phenobarbital, will be enrolled in order to expose a total of at least 1,000 
subjects for at least 6 months.
Objectives
The objective is to evaluate the safety and pharmacokinetics of YKP3089 
and concomitant AEDs when administered as adjunctive therapy for the 
treatment of partial seizures. The evaluations will include:
1. Phenytoin-YKP3089 interaction
2. Phenobarbital-YKP3089 interaction
3. Long term safety of YKP3089 as adjunctive therapy in partial onset 
seizures 
4. Population pharmacokinetics of YKP3089 and concomitant AEDs.
Inclusion and 
exclusion criteria
Subjects to be enrolled in the study include:
1. Subjects on stable doses of phenytoin
2. Subjects on stable doses of phenobarbital
3. Subjects on stable doses of other concomitant AEDs
Subjects who meet all inclusion and no exclusion criteria listed in Section 
7.3 and Section 7.4 of the protocol are eligible to enroll.

2
LIST OF ABBREVIATIONS
AE
Adverse event
AED
Antiepileptic drug
ALT
Alanine aminotransferase 
AST
Aspartate aminotransferase 
AUC
Area under the plasma concentration versus time curve 
β-hCG
β-human chorionic gonadotropin
CBZ
Carbamazepine
CFR
Code of Federal Regulations
CNS
Central nervous system
C-SSRS
Columbia Suicide Severity Rating Scale
CT
Computed tomography
CYP
Cytochrome P450
DRESS 
Drug reaction (or rash) with eosinophilia and systemic symptoms
EC
Ethics committee
ECG
Electrocardiogram
eCRF
Electronic case report form
EEG
Electroencephalograph
FDA
Food and Drug Administration
GABA
Gamma-aminobutyric acid
GCP
Good Clinical Practice
ICH
International Conference on Harmonisation
IND
Investigational new drug
IRB
Institutional review board
IWRS
Interactive Web response system
kg
Kilogram
mg
Milligram
MRI
Magnetic resonance imaging
PHI
Protected health information
PI 
Principal Investigator
SAE
Serious adverse event
SKLSI
SK Life Science, Inc.
SUDEP
Sudden unexpected death in epilepsy
SUSAR
Suspected unexpected serious adverse reaction
VNS
Vagal nerve stimulator
VPA
Valproic acid (divalproex sodium)

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5 
June 20, 2019 
Page 61 of 135
3
STUDY ASSESSMENTS
Table 1. Study Assessment Flow Chart

4
BACKGROUND AND DOSE SELECTION
4.1
Introduction
This is a protocol for a human research study. This study is being conducted according to US and 
international standards of Good Clinical Practice (GCP) (Food & Drug Administration [FDA] Title 
21 Part 312 and International Conference on Harmonisation [ICH] guidelines), applicable 
government regulations, and Institutional research policies and procedures.
4.2
Considerations for Studies of Epilepsy
According to the World Health Organization, epilepsy afflicts more than 50 million people 
worldwide.1 Epilepsy leads to an increased risk of injury from accidents and an increased rate of 
mortality and has a significant impact on quality of life. First-generation antiepileptic drugs 
(AEDs) are still commonly used, even though they can produce a diversity of serious adverse 
events (SAEs). New AEDs approved since the early 1990s have shown an improved tolerability 
profile. Nonetheless, approximately 30% of epilepsy cases, particularly those with partial seizures, 
are refractory to treatment. Many of these patients are taking multiple antiepileptic drugs. It is 
important to understand any interaction that occurs between them as well as the long term safety 
profile of YKP3089 when given as adjunctive therapy.
Choice of add-on (adjunctive) design. The initial evaluation of a new antiepileptic drug generally 
includes a determination of its efficacy in reducing the frequency of seizures in adults who are 
refractory to treatment with other AEDs.2,3,4 Because of the risk of exacerbation of seizure severity 
and frequency upon withdrawal of long-term AED therapy, even in the refractory population, the 
new AED under study is added to the existing therapy instead of being used as monotherapy.
Because partial seizures represent the most common type in both adults and children and claim a 
disproportionate share of medically refractory cases, they have been the most frequently selected 
seizure type in the investigation of new AEDs.

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5
June 20, 2019
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4.3
Background 
4.3.1
YKP3089 Structure
YKP3089 is (R)-(+)-1-(2-chloro-phenyl)-2-tetrazol-2-yl-ethyl ester, which has the chemical 
formula C10 H10 Cl N5. YKP3089 is being provided in tablets that contain 50 or 100 mg of the 
active ingredient. It is a novel small molecule of molecular weight 267.68. Its structure is shown 
in Figure 1.
Figure 1. Structure of YKP3089
YKP3089 is a novel small molecule with open INDs for epilepsy (76,809), neuropathic pain (IND 
108,178), and anxiety (IND 72,741). It is currently in Phase 2 of development as an antiepileptic 
agent for partial onset seizures. YKP3089 was shown to be active in standard animal models of 
epilepsy, neuropathic pain, and anxiety when administered orally. 
4.4
Pharmacology
Receptor test systems have shown that YKP3089 does not show significant activity at any of the 
classical receptor types (eg, adrenergic, GABAergic) or pharmacologic receptors. However, in 
vitro electrophysiology assays showed YKP3089 to be an inhibitor of the slow inactivated state of 
sodium channels. YKP3089 may also increase inhibitory synaptic transmission by facilitating the 
release of GABA.
4.4.1
Absorption, Distribution, Metabolism, and Excretion
In vitro studies with human microsomes revealed that YKP3089 directly inhibited CYP2B6 (IC50
= 280 μM), CYP2C19 (IC50 = 170 μM), and CYP3A4/5 (as measured by testosterone 6β-
hydroxylation, IC50 = 890 μM; and midazolam 1′-hydroxylation, IC50 = 720 μM). These IC50

SK Life Science Inc
CONFIDENTIAL
Protocol YKP3089C021, Amendment 5 
June 20, 2019 
Page 69 of 135
the reciprocal effects of phenytoin and YKP3089, plasma phenytoin exposure increased with co-
administration of YKP3089 by 67% (Cmax) and 84% (AUC) and plasma YKP3089 exposure (Cmax,
AUC) decreased with co-administration of phenytoin by 27 - 28%. Preliminary results of a drug 
interaction study examining the reciprocal effects of phenobarbital and YKP3089, plasma 
phenobarbital exposure increased with co-administration of YKP3089 by 34% (Cmax) and 37%
(AUC) and plasma YKP3089 exposure (Cmax, AUC) decreased with co-administration of 
phenobarbital by 10-15% based on historical controls.
4.4.2
Safety Pharmacology and Toxicity Studies
YKP3089 has been assessed in a large number of safety pharmacology and toxicology studies 
including single-dose toxicity, repeat-dose toxicity, cardiotoxicity, genetic toxicity, and 
reproductive toxicity studies in animals. Safety pharmacology studies showed that the doses that 
produced beneficial central nervous system (CNS) effects of YKP3089 in animal models do not 
result in obvious negative effects on the CNS. No evidence of cardiovascular effects was observed 
by telemetric electrocardiography in male monkeys. 
Details of the preclinical safety and toxicity studies of YKP3089 can be found in the Investigator’s
Brochure. The most common AEs in preclinical studies of YKP3089 involved the central nervous 
system (CNS).
Reproductive toxicity studies showed adverse effects on reproductive performance when the 
dosage of YKP3089 was high enough to induce maternal toxicity, as evidenced by decreased food 
consumption and decreased body weight. However, there was no evidence of teratogenicity.
The results of standard genotoxicity studies of YKP3089 were negative. There is no evidence of 
carcinogenicity in standard testing of two rodent species.
4.4.3
Clinical Safety and Efficacy
Cumulatively, 953 subjects have been exposed to YKP3089 in a total of 14 Phase 1 and 3 Phase 2 
clinical studies.
The results of the first completed double-blind, randomized, placebo-controlled trial in subjects 
with partial epilepsy demonstrated that treatment with 200 mg of YKP3089 produced a highly 

statistically significant reduction in the frequency of partial onset seizures (Table 2) and seizure 
free rates (Table 3). YKP3089 was generally well-tolerated.  The rate of adverse event withdrawals 
was similar between the YKP3089 and placebo groups.  No life threatening serious adverse events 
were identified among YKP3089-treated subjects. The most common central nervous system 
adverse events in the YKP3089 group were somnolence, dizziness, fatigue, and gait disorder.
The second randomized, double-blind, placebo-controlled, dose response trial with a 18 week 
treatment period enrolled a total of 437 subjects, 108 in a 100 mg YKP3089 group, 110 in a 200 
mg YKP3089 group, 111 in a 400 mg YKP3089 group and 109 in a placebo group. The trial 
confirmed that treatment with 200 mg/day and 400mg/day of YKP3089 produces a highly 
statistically significant reduction in the frequency of partial onset seizures in patients with partial 
epilepsy (Table 2) and high seizure free rates (Table 4).
Table 2:  Effect Size of Median Percent Reduction and 50% Responder Rate Relative to 
Placebo in YKP3089 Trials
 
YKP3089C013 
Study 
YKP3089C017 
Study 
Dose 
200mg 
100mg 
200mg 
400mg 
Median Percent 
Reduction 
34.1 
11.5 
31.0 
31.0 
50% Responder 
Rate 
28.2 
19.0 
35.2 
38.7 
P values in all comparisons were <0.01
Table 3:  Seizure free Rates (Completer Population) at 200mg in YKP3089C013
Responder Type
6 Week Maintenance Phase
% Responders  
placebo
N = 99
% Responders YKP3089
N = 102
P value
100%
9.1
27.5
0.0003
Table 4:  Seizure Free Rates (Completer Population) in YKP3089C017
Responder 
Type
12 Week Maintenance Phase
% Responder
s
% Responders
(YKP3089 100 mg)
% Responders 
% Responders 

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June 20, 2019 
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There have been three cases of DRESS syndrome in YKP3089 clinical studies.
Rash and hypersensitivityDuring the YKP3089 development program there have been other 
reports of rash and hypersensitivity reactions, some resulting in hospitalization and/or 
discontinuation. An aggregate analysis of the rate of rash/hypersensitivity and DRESS in subjects 
exposed to multiple doses of YKP3089 was performed Table 5.
Table 5:  Rate of rash/hypersensitivity and DRESS in subjects exposed to multiple doses of 
YKP3089  
Starting Dose 50 mg 
with 50 mg Increase 
Every 2 Weeks
Starting dose 50 mg 
with 50 mg Increase 
Every 1 Week
Starting dose  100 mg 
or more with 100 mg 
Increase Every 5 to 7 
Days
Total
Active
Placebo
Active
Placebo
Active
Placebo
Active
Placebo
Subjects 
Exposed
120
112
363
152
350
37
833
301
Rash/hyper
sensitivity
N (%)
1 (0.8%)
3 (2.7%)
18(5.0%)
4(2.6%)
19 (5.4%)
3 (8.1%) 38 (4.6%)
10
(3.3%)
Dropouts  
1 (0.8%)
0
8 (2.2%)
1 (0.6%)
9 (2.5%)
0
18 (2.2%) 1 (0.3%)
DRESS
0
0
1
0
2
0
3
0
The results of the aggregate analysis suggest that lower YKP3089 starting dose and slower 
titration rate are associated with lower risk of rash/hypersensitivity.  
x
When YKP3089 dosing was increased weekly or faster, the rate of rash/hypersensitivity 
reactions was approximately 5%.  When YKP3089 was increased by 50 mg increments 
every 2 weeks, only one case (0.8%) of hypersensitivity reactions was observed.  
Two cases DRESS occurred when the first dose of YKP3089 was 100 mg (epilepsy study) or 
200 mg (healthy volunteer) followed by rapid titration.  The third case, in a healthy volunteer, 
occurred in a study where the initial dose of YKP3089 was 50 mg/day for 1 week followed by 50 
mg weekly increments. 

4.5
Rationale
4.5.1
Study Rationale
Approximately 30% of epilepsy cases, particularly those with partial seizures, are refractory to 
treatment. Many of these patients are taking multiple antiepileptic drugs. It is important to 
understand any interaction that occurs between them as well as the long term safety profile of 
YKP3089 when given as adjunctive therapy. 
Based on healthy volunteer studies with phenytoin and phenobarbital, YKP3089 increases plasma 
levels of phenobarbital and phenytoin levels. A portion of this open label safety and 
pharmacokinetic study is designed to understand the impact of adding YKP3089 to an AED 
regimen including either phenytoin or phenobarbital in subjects with partial epilepsy.
In addition this open label and pharmacokinetic study will enroll subjects taking concomitant 
AEDs other than phenytoin or phenobarbital to study long term safety and obtain population 
pharmacokinetic data.
A review of the YKP3089 safety database confirmed three cases of DRESS syndrome among the 
953 subjects exposed to the drug. 
In order to further characterize the safety profile of YKP3089 while minimizing risk to patients, 
the following plan was developed:
1. Low starting dose (12.5 mg) and slower titration (dose increase every two weeks) 
2. Close monitoring (visits every two weeks) during the first 4 months of treatment to allow 
early detection of suspected cases of hypersensitivity reaction  
3. Evaluation of suspected cases of hypersensitivity reaction to facilitate accurate diagnosis 
4. Care of subjects with hypersensitivity reactions to minimize consequences 

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June 20, 2019 
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4.5.2
Dose Justification
The target dose of 200 mg/day is based on the efficacy, safety, and tolerability of YKP3089 in 
previously completed and ongoing studies.  
Initiating treatment with YKP3089 at 12.5 mg and then increasing the dose every two weeks is 
likely to further reduce the risk of many side effects including hypersensitivity reactions. Slowing 
the titration rates of pharmaceuticals is a well-known procedure for mitigating risk of adverse 
reactions. Reducing the initial dose and slowing the titration can reduce many central nervous 
system or gastrointestinal side effects.   It has been demonstrated that lowering the initial dose and 
slowing the titration rate can mitigate the occurrence of rash and possibly the rate of more serious 
and potentially life threatening adverse cutaneous reactions (Zaccara G, 2007). 
After initiating treatment with YKP3089 for two weeks at 12.5 mg and then for two weeks at  
25mg YKP3089, subjects taking phenytoin or phenobarbital will titrate YKP3089 upward at a rate 
of 50mg every other week to a target dose of 200mg/day. This titration is appropriate for this 
portion of the study because of the known interactions between YKP3089 200mg and phenytoin 
and phenobarbital. Titrating by 50mg of YKP3089 every other week to steady state will allow 
better understanding of the clinical impact of any interaction and allow for dosage adjustment of 
phenytoin or phenobarbital.
Subjects taking concomitant AEDs other than phenytoin or phenobarbital will titrate YKP3089 
upward at the same rate to a target dose of 200mg/day.
After reaching a target dose of 200mg, all subjects will be allowed to titrate up to a maximum dose 
of 400mg/day of YKP3089. A maximum dose of 400mg/day is justified by the additional efficacy 
seen in the subjects randomized to 400mg/day in the completed dose response study. Seizure free 
rate effect size in this group approached 20% during the maintenance phase.  
4.6
Potential Risks and Benefits
Cumulatively, 953 subjects have been exposed to YKP3089 in a total of 14 Phase 1 and 3 Phase 2 
clinical studies.
The potential risks in this study includes,

1.
Phenytoin dose related toxicity
2.
Risk of phenytoin hypersensitivity syndrome
3. Phenobarbital dose related toxicity 
4. Rash / hypersensitivity related to YKP3089 exposure
5.
DRESS syndrome related to YKP3089 exposure
6. YKP3089 dose related toxicities
Uncontrolled partial epilepsy is a life threatening disease with significant morbidity and elevated 
standard mortality rates.
The early signs and symptoms associated with hypersensitivity reaction that may progress to 
DRESS are readily identifiable by patients and clinicians. When detected and adequately 
managed, progression to DRESS can be prevented or reversed.   The potential benefits of
YKP3089 include significant partial seizure frequency reduction and substantial seizure free 
rates (~18%) in patients who continue to suffer seizures despite history of treatment with 
multiple AEDs. The current benefit/risk profile in conjunction with the risk minimization 
measures support the enrollment of partial epilepsy patients into this open-label study to assess 
the profile of YKP3089 as a potential antiepileptic drug
5
STUDY OBJECTIVES 
The objective is to evaluate the safety and pharmacokinetics of YKP3089 and concomitant AEDs 
when administered as adjunctive therapy for the treatment of partial seizures. The evaluations will 
include:
1. Phenytoin-YKP3089 interaction
2. Phenobarbital-YKP3089 interaction 
3. Long term safety of YKP3089 as adjunctive therapy in subjects with partial onset seizures 
4. Population pharmacokinetics of YKP3089 and concomitant AEDs

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June 20, 2019 
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6
STUDY DESIGN
6.1
Overview
This multicenter, open label study in subjects with poorly controlled partial seizures will consist 
of a screening period, open-label titration phase, open label maintenance phase and a taper and 
follow up. At least 20 subjects taking phenytoin and at least 20 subjects taking phenobarbital will 
be enrolled. Additional subjects taking AEDs other than phenytoin or phenobarbital, will be 
enrolled in order to expose at least 1,000 subjects for 6 months to further evaluate long term safety.
6.1.1
Screening Period
The screening period for subjects on stable doses of phenytoin or stable doses of phenobarbital or 
stable doses of other concomitant AEDs will be up to 21 days. 
During Screening, assessments will be performed according to the study assessments listed in 
Table 1 to determine eligibility for the study. Each subject will be informed of his or her rights, 
and the subject or his or her legally authorized representative must sign an informed consent 
document indicating understanding of the purpose of the study and required procedures and 
indicating willingness to participate in the study.
6.1.2
Open label Treatment Period
The open label treatment period will consist of a 12 week titration phase followed by an open label 
maintenance phase.
6.1.2.1
Titration Phase
Subjects taking phenytoin or phenobarbital
The titration phase for subjects on stable doses of phenytoin or stable doses of phenobarbital will 
be 12 weeks. During the 12-week up-titration phase, subjects will increase YKP3089 dose every 
2 weeks to a target dose of 200mg/day as described in Table 6.
Table 6. YKP3089 Initial Up-Titration for subjects on phenytoin and phenobarbital
YKP3089 dose (mg/day)

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To improve tolerability, the investigator may instruct the subject to take the dose of YKP3089 in 
the evening. The investigator may alter the timing or amount of an individual dose of any other 
concomitant AED, but the total daily dose and dosing frequency of any other concomitant AED
must remain unchanged during the titration phase.
Subjects taking concomitant AEDs other than phenytoin or phenobarbital
The titration phase for subjects on stable doses of other concomitant AEDs will be 12 weeks. 
Increasing doses of YKP3089 will be administered (50, 100, 150 and 200mg/day) at 2-week 
intervals as described in Table7.
Table7. YKP3089 Initial Up-Titration for subjects on concomitant AEDs other than 
phenytoin or phenobarbital
YKP3089 dose (mg/day)
Week 1 & 2 
Week 3 & 4
Week 5 & 6
Week 7 & 8
Week 9 & 10
Week 11 & 12
12.5
25
50
100
150
200
Prior to initiating YKP3089, subjects at US sites only will have trough concomitant AED levels
(oxcarbazepine, topiramate, lamotrigine, lacosamide, clobazam, perampanel and levetiracetam
only) drawn at Visit 2. Sites must instruct the subject and schedule the visit accordingly to obtain 
a trough level. Also the blood must be collected before first dose of YKP3089.  To improve 
tolerability, the investigator may instruct the subject to take the dose of YKP3089 in the evening. 
The investigator may add, remove, or adjust the dosage of any concomitant AEDs, as clinically 
indicated (see Table 8 below). Monotherapy with YKP3089 will not be allowed. If clinically 
indicated, titration can be stopped below 200mg/day. A minimum dose of 50mg/day is necessary 
to continue in the study.
Table 8. Dose Adjustment Rules during Titration Phase
Cohort Æ
Subjects taking Phenytoin or 
Phenobarbital
Subjects taking AEDs other 
than Phenytoin or 
Phenobarbital
Adjustments of any 
Concomitant AEDs
Not Allowed
Allowed
Adjustments of YKP3089
Not Allowed
Allowed

the dose of study medication in the evening or divide the total daily dose into 2 doses. Subjects 
will follow the schedule of study visits and assessments detailed in Table 1.
After 12 months of participation in the open-label treatment period, subjects will be re-evaluated. 
Those who are benefiting from treatment with YKP3089 may continue use of the drug at the
discretion of the investigator, until development is stopped by SK Life Science Inc or the product 
is approved for marketing, or anytime at the discretion of SK Life Science Inc.
Table 9. Dose Adjustment Rules during Maintenance Phase
Cohort Æ
Subjects taking Phenytoin or 
Phenobarbital
Subjects taking AEDs other 
than Phenytoin or 
Phenobarbital
Adjustments of any 
Concomitant AEDs
Allowed
Allowed
Adjustments of YKP3089
Allowed
Allowed
Adjustment of Phenytoin or 
Phenobarbital 
Allowed
Not Applicable
6.1.2.3
Taper and follow up
Subjects who are withdrawn from the open-label treatment period will taper YKP3089 according 
to the schedule described in Table 10, unless for safety reasons the investigator judges it necessary 
to discontinue study drug immediately. For subjects taking phenytoin or phenobarbital, 
discontinuing YKP3089 may reduce the plasma concentration of these AEDs. Doses of phenytoin 
or phenobarbital may need to be adjusted as clinically indicated.
Table 10. Study Drug Taper Schedule for Subjects Completing Open-Label Treatment 
Final open-label dose of 
YKP3089 (mg/day)
YKP3089 Dose During Taper (mg/day)
Week 1
Week 2
Week 3
50 or 100
None
150 or 200
100
None
None
250 or 300 
200
100
None
350 or 400
300
200
100

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The follow up visit will take place 14 days after the subject’s last dose, following taper and 
discontinuation of YKP3089; at any time during the open-label treatment; or after 12 months of 
open-label treatment if there is no additional treatment beyond that point.
6.2
Study Endpoints
6.2.1
Pharmacokinetic Endpoints
Sparse PK blood samples will be collected to evaluate YKP3089 and relevant concomitant AED 
exposure using a population pharmacokinetics approach. This will allow for the investigation of 
potential effects of covariates on the pharmacokinetics of YKP3089 or other concomitant AEDs. 
YKP3089 and other concomitant plasma concentration data collected from this study will be 
pooled with relevant data from other YKP3089 clinical studies for population PK analysis.
6.2.2
Safety Endpoints
Safety will be assessed by the nature, frequency, and severity of treatment-emergent spontaneously 
reported AEs, dropouts due to AEs, overall dropout rates, and changes from baseline in vital signs, 
physical exams, clinical laboratory evaluations, C-SSRS and 12-lead ECGs, in YKP3089-treated 
subjects.
7
SELECTION OF STUDY POPULATION
7.1
Study Population and Sites
This trial will be sponsored by SK Life Science Inc. in the United States and other countries.
7.2
Subject Recruitment
Subjects will be selected from the investigator’s existing patient population or may be referred by 
another physician. Sites may also advertise beyond their practice. All advertisements must be
approved by the Sponsor and governing ethics committee. Subjects who have provided signed 
informed consent will need to complete the Screening visit assessments to confirm eligibility for 
the study.

7.3
Inclusion Criteria
Subjects must satisfy all of the following criteria to be enrolled in the study:
1.
Male or female and greater than or equal to 18 years of age at the time of signing the informed 
consent. The upper age limit is 70 years inclusive.
2.
Weight at least 40 kg
3.
Written informed consent signed by the subject or legal guardian prior to entering the study in 
accordance with the ICH GCP guidelines. If the written informed consent is provided by the legal 
guardian because the subject is unable to do so, a written or verbal assent from the subject must 
also be obtained. In Germany, only the subject may sign the informed consent form in accordance 
with ICH guidelines.
4.
A diagnosis of partial epilepsy according to the International League Against Epilepsy’s 
Classification of Epileptic Seizures. Diagnosis should have been established by clinical history 
and an electroencephalogram (EEG) that is consistent with localization related epilepsy; normal 
interictal EEGs will be allowed provided that the subject meets the other diagnosis criterion (ie, 
clinical history).
5.
Have uncontrolled partial seizures and require additional AED therapy despite having been treated 
with at least one AED within approximately the last 2 years. 
6.
Currently on stable antiepileptic treatment regimen: 
g) Subject must have been receiving stable doses of 1 to 3 AEDs for at least 3 weeks prior to 
Visit 2.
h) Vagal nerve stimulator (VNS) or deep brain stimulator (DBS) will not be counted as an 
AED; however, the parameters must remain stable for at least 4 weeks prior to baseline.
The VNS or DBS must have been implanted at least 5 months prior to Visit 1.
i)
Benzodiazepines taken at least once per week during the 1 month prior to Visit 1 for 
epilepsy, or for anxiety or sleep disorder, will be counted as 1 AED and must be 
continued unchanged throughout the study. Therefore only a maximum of 2 additional 
approved AEDs will be allowed.

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June 20, 2019 
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7.
Computed tomography (CT) or magnetic resonance imaging (MRI) scan performed within the past 
10 years that ruled out a progressive cause of epilepsy. If a CT or MRI has not been performed 
within the past 10 years, one must be performed prior to dosing.
8.
Ability to reach subject by telephone.
9.
Use of an acceptable form of birth control by female subjects of childbearing potential (see Section 
7.5).
Any potential exception to inclusion criteria allowing de minimis (clinically trivial and 
meaningless) variations must be approved by the medical monitor. 
7.4
Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from participating in the study:
1.
History of any serious drug-induced hypersensitivity reaction (including but not limited to Stevens 
Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic 
symptoms) or any drug-related rash requiring hospitalization.
2.
History of any drug-induced rash or hypersensitivity reaction with documented nature of the rash 
or hypersensitivity reaction.
3.
History of a first degree relative with a serious cutaneous drug-induced adverse reaction.
4.
History of serious systemic disease, including hepatic insufficiency, renal insufficiency, a 
malignant neoplasm, any disorder in which prognosis for survival is less than 3 months, or any 
disorder which in the judgment of the investigator will place the subject at excessive risk by 
participation in a controlled trial.
5.
Subjects taking phenytoin must not be taking phenobarbital or primidone; subjects taking 
phenobarbital must not be taking phenytoin or primidone.
6.
Subjects taking concomitant AEDs other than phenytoin or phenobarbital, must not be taking 
phenytoin or phenobarbital or primidone.
7.
Subjects with clinical evidence of phenytoin or phenobarbital toxicity.

7.5
Birth Control Methods Allowable for Enrollment of Subjects
Sexually active female subjects of reproductive potential must practice an approved method of 
contraception during the entire study and for 30 days after the last dose of study medication. 
Hormonal contraceptives alone will not be considered an adequate method of contraception.
Women of childbearing/reproductive potential are defined as: Any female who has experienced 
menarche and does not meet the criteria for “Women Not of Childbearing Potential”. Women not 
of childbearing potential are defined as women who are postmenopausal or permanently sterilised 
(e.g. tubal occlusion, hysterectomy, bilateral salpingectomy).
Acceptable methods include: 
x
Hormonal contraception (for at least 3 months prior to Visit 1) in combination with a barrier 
method.
x
Intrauterine device (placement at least 3 months prior to Screening visit)
x
Diaphragm with spermicide
x
Cervical cap
x
Condoms with contraceptive gel/foam or cream 
x
Surgical sterilization (tubal ligation at least 6 months prior to screening or partner who has had 
vasectomy at least 6 months prior to screening)
x
Postmenopausal (as defined by absent menses for at least 12 months)
x
Abstinence; however, if the subject becomes sexually active, 1 of the above methods must be 
utilized.
There is no need for male subjects enrolled in YKP3089C021 study to use contraception with 
partners of childbearing potential during their participation in the study.

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8
TREATMENTS
8.1
Study Medication Information
8.1.1
Description of Study Medication 
8.1.1.1
Physical Description of the Drug
 
12.5mg 
 
25mg 
 
50mg 
 
100mg 
 
¼ inch in diameter, 
round biconvex, 
tablets debossed 
with “SK” on one 
side and “12” on 
the other side.
 
 
10mm in diameter, 
round, biconvex 
plain-faced tablets 
scored on one side. 
 
10mm in diameter, 
round, biconvex 
plain-faced tablets 
scored on one side. 
 
10mm in diameter, 
round, biconvex 
plain-faced tablets 
scored on one side. 
8.1.1.2
Testing
The sponsor is responsible for testing investigational product to establish stability and storage 
conditions. The storage specification provided on the labeling reflect results of this testing.
8.1.1.3
Packaging and Labeling
YKP3089 will be packaged in high density polyethylene (HDPE) bottles each containing 30 tablets 
of either 12.5mg or 25mg or 100 tablets of either 50 mg or 100 mg.
8.1.2
Supply, Storage, Accountability, and Disposition of Study Medication
The Sponsor’s manufacturing facility will ship a sufficient supply of study medication to each 
study site directly or from a local depot. The clinical investigator has the responsibility for 
confirming that all study drug treatment supplies received by the site are inventoried and accounted 
for throughout the study. A drug receipt log is to be filled out and signed by the person accepting 
the shipment. It is important that the designated study staff count and verify that the shipment 
contains all the items noted in the shipment inventory. Any damaged or unusable study drug in a 

given shipment will be documented in the study files. The investigator must notify the study 
Sponsor of any damaged or unusable study treatments that were supplied to the investigator’s site.
Subjects or their legal representatives must be told to return all original containers (empty or 
containing study drug), which will be stored and disposed of according to Sponsor's instructions. 
Subjects or their legal representatives must also be told to keep study drugs in their original 
containers and not to combine the contents of different containers.
All study medication must be kept in a secure, locked area or locked cabinet with access restricted 
to designated study personnel. The tablets will be stored at room temperature in a dry area,
protected from light.
Study personnel will keep accurate records of the study medication dispensed to and used by each 
subject and be available for verification for the Sponsor's site monitor during on-site monitoring 
visits. The site monitor will periodically check the supplies of study medication held at the site to 
ensure accountability of all study medication used throughout the study.
At the conclusion of the study, a final inventory will be performed. Any discrepancies will be 
investigated, resolved, and documented prior to return to the Sponsor for destruction of study drug 
that has not been dispensed and study drug that has been dispensed and returned.
8.2
Screening and Study Drug Distribution
8.2.1.1
Screening Number
The subject will be assigned a screening number by IWRS after signing the informed consent form.
The screening number will be an 8-digit number in which the first 2 digits will signify the country, 
the third, fourth, and fifth digits will signify the site number in that country, and the last 3 digits 
will be a consecutive number, starting 101, assigned to subjects in the order in which they are 
screened. Thus, the third screened subject in the second site in the country given number 01 will 
have screening number 01002103. Screening number should not be reused. Re-screening is not 
allowed.

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8.2.1.2
Drug Dispensing
At each visit, the investigator will access the IWRS, enter his or her own user ID and PIN, and 
provide requested subject details (eg, subject’s year of birth). The IWRS will identify open label
bottles of tablets to be dispensed. Returned bottles may be re-dispensed to the same subject after 
drug accountability is performed.
Prior to dispensing, the investigator will record on each open label bottle label the subject number,
date dispensed, site number, phone contact, and investigator name.
In addition, the investigator will review the electronic case report form (eCRF) to make sure the
medication number printed on each bottle dispensed is populated in the system correctly.
At each visit, the investigator will record the exact dates and exact doses taken since the last visit 
in the case report form (eCRF). All dosing changes should be recorded in details.
8.3
Prior and Concomitant Treatments
Subjects must be on their current stable daily dosage of phenytoin or phenobarbital or any other 
concomitant AEDs for at least 3 weeks before Visit 2. They must continue taking the same brand 
of phenytoin or phenobarbital throughout the titration phase. 
Those subjects taking phenytoin every 24 hours will be instructed to take the dose at approximately 
8:00 a.m. beginning at least 7 days before Visit 2 and continue this regimen throughout the titration 
phase. On the day of Visit 2, subject should delay the morning dose until the trough phenytoin 
plasma sample is obtained. Subjects who are taking phenytoin every 24 hours at bedtime will need 
to switch to morning dosing at least 7 days before Visit 2. Subjects who take phenytoin every 12 
hours will be instructed to take their doses at approximately 8:00 a.m. and 8:00 p.m. beginning at 
least 7 days before Visit 2 and continue this regimen throughout the titration phase.
Those subjects taking phenobarbital every 24 hours will be instructed to take the dose at 
approximately 8:00 a.m. beginning at least 7 days before Visit 2 and continue this regimen 
throughout the titration phase. On the day of Visit 2, subject should delay the morning dose until 
the trough phenobarbital plasma sample is obtained. Subjects who are taking phenobarbital every 
24 hours at bedtime need not switch to morning dosing. Subjects who take phenobarbital every 12 

hours will be instructed to take their doses at approximately 8:00 a.m. and 8:00 p.m. beginning at 
least 7 days before Visit 2 and continue this regimen throughout the titration phase.
Intermittent rescue medication can be used during the open-label treatment period.
Subjects taking AEDs other than phenytoin or phenobarbital at the beginning of the study cannot 
add phenytoin or phenobarbital to the existing regimen.
8.4
Prohibited Medications or Devices
Medication
Not allowed
Allowed
x
Clopidogrel, fluvoxamine, 
amitriptyline, clomipramine, 
bupropion, methadone, 
ifosfamide, cyclophosphamide, 
efavirenz, natural progesterone
fosphenytoin, ethotoin, 
mephenytoin, primidone,  and 
diazepam
During the study and 
within 30 days prior to 
Visit 1
If taken any time before 30 days 
prior to Visit 1
x
Subjects taking phenytoin must 
not be taking phenobarbital or 
primidone; 
During the study and 
within 30 days prior to 
Visit 1
x
Subjects taking phenobarbital 
must not be taking phenytoin or 
primidone
During the study and 
within 30 days prior to 
Visit 1
x
Vigabatrin and ezogabine
During the study and 
within 1 year prior to 
Visit 1
If taken anytime 1 year before 
Visit 1 (see exclusion criteria for 
other restrictions specific to 
Vigabatrin and ezogabine)
x
Felbamate
During the study if 
felbamate was initiated 
within 18 months prior 
to Visit 1
If felbamate was initiated more 
than18 months prior to Visit 1
x
Investigational medications or
devices other than YKP3089 
During the study and 
within 30 days prior to 
Visit 1
If taken or used anytime 30 days 
before Visit 1
8.5
Dosing Instructions for Study Medication

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June 20, 2019 
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x
It is recommended that the study medication is taken once daily in the morning.  
x
In the event of poor tolerability, the investigator may instruct the subject to take the dose of 
study medication in the evening.
x
During maintenance phase, in the event of poor tolerability, the investigator may instruct the 
subject to divide the total daily dose of study medication into 2 doses.
x
Study medication can be taken with or without food.
x
Study medication must be swallowed, not chewed.
9
STUDY PROCEDURES AND ASSESSMENTS
Visit windows of ± 2 days allowed for Visits 3 through 10.
Visit windows of ± 7 days allowed for all other open-label visits.
9.1
Screening 
9.1.1
Visit 1, Day -21
As shown in Table 1, the following will be performed during Visit 1: 
x
Obtain informed consent (obtained from the subject prior to any study-related procedures)
x
Review and record inclusion and exclusion criteria
x
Record medical and seizure history and demographics
x
Record vital signs
x
Conduct full physical examination (see Appendix A), including height and weight
x
Conduct full neurologic examination (see Appendix B)
x
Administer C-SSRS (Baseline/Screening version) (see Appendix D: COLUMBIA SUICIDE 
SEVERITY RATING SCALE (Baseline/Screening))
x
Perform 12-lead ECG once
x
Perform serum pregnancy test (female subjects of childbearing potential; if positive, subject 
will not be enrolled)
x
Draw blood for laboratory safety assessment
x
Obtain urine for urinalysis

x
An MRI or CT scan will be performed during screening if the subject has not had a 
neuroimaging study within 10 years of Visit 1. This will be used to document the absence of 
an active brain lesion, and a copy of the report will be made available to the Sponsor
x
Include the EEG report in the source document. If an EEG report cannot be obtained, and the 
subject is otherwise eligible, an EEG may be performed during screening.
x
Record concomitant medications
x
Schedule Visit 2 to occur within 3 weeks of Visit 1
9.1.2
Visit 2, Day 1
All subjects who have not discontinued will be scheduled to appear at the clinic for Visit 2. At
Visit 2, subjects who continue to meet all of the inclusion criteria and none of the exclusion criteria 
will receive study drug.
As shown in Table 1, the following will be performed at Visit 2:
x
Review and record inclusion and exclusion criteria 
x
Record vital signs
x
Conduct brief neurologic examination if required (Appendix C)
x
Administer C-SSRS (Since Last Visit version) (Appendix E)
x
Perform urine pregnancy test (for female subjects of childbearing potential)
x
Record concomitant medications
x
Record AEs
x
For subjects taking phenytoin or phenobarbital, draw blood for phenytoin or phenobarbital
trough levels
x
For subjects taking concomitant AEDs other than phenytoin or phenobarbital at US sites only,
draw blood for concomitant AEDs (oxcarbazepine, topiramate, lamotrigine, lacosamide, 
clobazam, perampanel and levetiracetam only) levels
x
Dispense study drug as instructed by IWRS if all of the inclusion criteria and none of the 
exclusion criteria are met

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x
The subject may take the first dose of the study medication the same day or the next morning.
If the investigator wants to observe the subject after the first dose at the clinic, the first dose 
can be administered at the site after all other Visit 2 procedures have been completed
x
Schedule a return to occur in 2 weeks for Visit 3
x
Dispense laminated Hypersensitivity Information safety card
x
Call subject in approximately one week to check for any adverse events
9.1.3
Visit 3, Day 15
As shown in Table 1, the following will be performed at Visit 3:
x
Record vital signs
x
Perform limited physical exam for signs of hypersensitivity such as rash, swelling, 
lymphadenopathy and fever
x
Conduct brief neurologic examination if required
x
Draw blood for laboratory safety assessment
x
Administer C-SSRS (Since Last Visit version)
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
Dispense study drug as instructed by IWRS
x
Schedule a return to occur in 2 weeks for Visit 4
x
Check and dispense laminated Hypersensitivity Information safety card
x
Call subject in approximately one week to check for any adverse events
9.1.4
Visit 4, Day 29
As shown in Table 1, the following will be performed at Visit 4:
x
Record vital signs
x
Measure weight
x
Perform limited physical exam for signs of hypersensitivity such as rash, swelling, 
lymphadenopathy and fever

x
Conduct brief neurologic examination if required
x
Administer C-SSRS (Since Last Visit version)
x
Draw blood for laboratory safety assessment
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
For subjects taking phenytoin or phenobarbital, draw blood for phenytoin or phenobarbital
levels. Two blood samples will be collected: For subjects taking phenytoin or phenobarbital in 
the morning and coming into the visits in the morning, the first blood draw will be collected 
upon subjects’ arrival to the study unit; the second blood draw should be collected within 30 
minutes to 2 hours after the medication is taken. 
x
Dispense study drug as instructed by IWRS
x
Schedule a return to occur in 2 weeks for Visit 5
x
Check and dispense laminated Hypersensitivity Information safety card
x
Call subject in approximately one week to check for any adverse events
9.1.5
Visit 5, Day 43
As shown in Table 1, the following will be performed at Visit 5:
x
Record vital signs
x
Perform limited physical exam for signs of hypersensitivity such as rash, swelling, 
lymphadenopathy and fever
x
Conduct brief neurologic examination if required
x
Draw blood for laboratory safety assessment
x
Administer C-SSRS (Since Last Visit version)
x
Perform urine pregnancy test (for female subjects of childbearing potential)
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
For subjects taking phenytoin or phenobarbital, draw blood for phenytoin or phenobarbital 
levels. Two blood samples will be collected: For subjects taking phenytoin or phenobarbital in 

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the morning and coming into the visits in the morning, the first blood draw will be collected 
upon subjects’ arrival to the study unit; the second blood draw should be collected within 30 
minutes to 2 hours after the medication is taken. 
x
Dispense study drug as instructed by IWRS
x
Schedule a return to occur in 2 weeks for Visit 6
x
Check and dispense laminated Hypersensitivity Information safety card
x
Call subject in approximately one week to check for any adverse events
9.1.6
Visit 6, Day 57
As shown in Table 1, the following will be assessed at Visit 6:
x
Record vital signs
x
Perform limited physical exam for signs of hypersensitivity such as rash, swelling, 
lymphadenopathy and fever
x
Conduct brief neurologic examination if required
x
Administer C-SSRS (Since Last Visit version)
x
Draw blood for laboratory safety assessment
x
For subjects taking phenytoin or phenobarbital, draw blood for phenytoin or phenobarbital 
levels. Two blood samples will be collected: For subjects taking phenytoin or phenobarbital in 
the morning and coming into the visits in the morning, the first blood draw will be collected 
upon subjects’ arrival to the study unit; the second blood draw should be collected within 30 
minutes to 2 hours after the medication is taken. 
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
Dispense study drug as instructed by IWRS.
x
Schedule a return to occur in 2 weeks for Visit 7
x
Check and dispense laminated Hypersensitivity Information safety card
x
Call subject in approximately one week to check for any adverse events

9.1.7
Visit 7, Day 71
As shown in Table 1, the following will be assessed at Visit 7:
x
Record vital signs 
x
Perform limited physical exam for signs of hypersensitivity such as rash, swelling, 
lymphadenopathy and fever
x
Conduct brief neurologic examination if required
x
Administer C-SSRS (Since Last Visit version)
x
Draw blood for laboratory safety assessment
x
For subjects taking phenytoin or phenobarbital, draw blood for phenytoin or phenobarbital 
levels. Two blood samples will be collected: For subjects taking phenytoin or phenobarbital in 
the morning and coming into the visits in the morning, the first blood draw will be collected 
upon subjects’ arrival to the study unit; the second blood draw should be collected within 30 
minutes to 2 hours after the medication is taken. 
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
Dispense study drug as instructed by IWRS.
x
Schedule a return to occur in 2 weeks for Visit 8
x
Check and dispense laminated Hypersensitivity Information safety card
x
Call subject in approximately one week to check for any adverse events
9.1.8
Visit 8, Day 85
As shown in Table 1, the following will be assessed at Visit 8:
x
Record vital signs 
x
Perform limited physical exam for signs of hypersensitivity such as rash, swelling, 
lymphadenopathy and fever
x
Conduct brief neurologic examination if required
x
Administer C-SSRS (Since Last Visit version)

9.1.9
Visit 9, Day 99
As shown in Table 1, the following will be assessed at Visit 9:
x
Record vital signs 
x
Perform limited physical exam for signs of hypersensitivity such as rash, swelling, 
lymphadenopathy and fever
x
Conduct brief neurologic examination if required
x
Administer C-SSRS (Since Last Visit version)
x
Perform urine pregnancy test (for female subjects of childbearing potential)
x
Draw blood for laboratory safety assessment
x
For subjects taking phenytoin or phenobarbital globally and concomitant AEDs other than 
phenytoin or phenobarbital in US, draw blood for YKP3089 levels. Two blood samples will 
be collected: For subjects taking YKP3089 in the morning and coming into the visits in the 
morning, the first blood draw will be collected upon subjects’ arrival to the study unit; the 
second blood draw should be collected within 30 minutes to 2 hours after the medication is 
taken. 
x
For subject taking concomitant AEDs other than phenytoin or phenobarbital at US sites only,
draw blood for concomitant AED levels (oxcarbazepine, topiramate, lamotrigine, lacosamide, 
clobazam, perampanel and levetiracetam only). Two blood samples will be collected: For 
subjects taking concomitant AEDs in the morning and coming into the visits in the morning, 
the first blood draw will be collected upon subjects’ arrival to the study unit; the second blood 
draw should be collected within 30 minutes to 2 hours after the medication is taken. For 
patients that are taking concomitant AEDs in the afternoon and/or coming into the visits in the 
afternoon, the first blood draw will be collected upon subjects’ arrival to the study unit; the 
second blood draw should be collected within 30 minutes to 2 hours after the first blood draw 
with timing of the dose, blood draws and strength of previous dose clearly documented.
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
Dispense study drug as instructed by IWRS.

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x
Schedule a return to occur in 2 weeks for Visit 10
x
Check and dispense laminated Hypersensitivity Information safety card
x
Call subject in approximately one week to check for any adverse events
9.1.10
Visit 10, Day 113
As shown in Table 1, the following will be assessed at Visit 10:
x
Record vital signs
x
Perform limited physical exam for signs of hypersensitivity such as rash, swelling, 
lymphadenopathy and fever
x
Conduct brief neurologic examination if required
x
Administer C-SSRS (Since Last Visit version)
x
Draw blood for laboratory safety assessment
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
Dispense study drug as instructed by IWRS.
x
Schedule a return to occur in 4-5 weeks for Visit 11
9.1.11
Visit 11, Day 143
As shown in Table 1, the following will be performed at Visit 11:
x
Record vital signs
x
Conduct brief neurologic exam if required
x
Administer C-SSRS (Since Last Visit version)
x
Perform urine pregnancy test (for female subjects of child-bearing potential)
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
Dispense study drug as instructed by IWRS.
x
Schedule a return to occur in 8-9 weeks for Visit 12

9.1.12
Visit 12, Day 203
As shown in Table 1, the following will be performed at Visit 12:
x
Record vital signs
x
Measure weight
x
Perform brief neurologic examination if required
x
Administer C-SSRS (Since Last Visit version)
x
Perform urine pregnancy test (for female subjects of child-bearing potential)
x
Draw blood for laboratory safety assessment
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
Dispense study drug as instructed by IWRS
x
Schedule a return to occur in 8-9 weeks for Visit 13
9.1.13
Visit 13, Day 263
As shown in Table 1, the following will be performed at Visit 13:
x
Record vital signs 
x
Conduct brief neurologic exam if required
x
Administer C-SSRS (Since Last Visit version)
x
Perform urine pregnancy test (for female subjects of child-bearing potential)
x
Draw blood for laboratory safety assessment
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
Dispense study drug as instructed by IWRS.
x
Schedule a return to occur in 14-15 weeks for Visit 14

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9.1.14
Visit 14 or Termination from study—Taper Visit
As shown in Table 1, the following will be performed at Visit 14 or at the time of early termination 
from the study.
x
Record vital signs
x
Measure weight
x
Conduct full physical examination
x
Conduct full neurologic examination
x
Administer C-SSRS (Since Last Visit version)
x
Perform 12-lead ECG once
x
Perform urine pregnancy test (for female subjects of childbearing potential)
x
Draw blood for laboratory safety assessment
x
Obtain urine for urinalysis
x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
For subjects who completed 1 year of open-label treatment, determine whether the subject is 
benefitting from open-label treatment with YKP3089 
For subjects who are benefitting from open-label treatment:
x
Dispense open-label medication 
x
Schedule a return to occur in 3 months for next visit
x
See section 9.1.16 for further instructions
For subjects who are not benefitting from open-label treatment or leaving the open-label 
treatment due to any reasons at any time:
x
Dispense taper open-label study drug bottles as instructed by IWRS if needed
x
Schedule a return to occur in 2 weeks of the last dose for Visit 15 if tapered
x
Schedule a return to occur in 2 weeks for Visit 15 if not tapered

9.1.15
Visit 15, End of Study Follow-up (14 days from the last dose)
Visit 15 represents the Follow-up Visit after discontinuation of study drug. This final visit will 
take place 14 days after the subject’s last dose of YKP3089—at any time during the open-label 
treatment or after 12 months of open-label treatment if there is no additional treatment beyond that 
point.
As shown in Table 1, the following assessments will be performed at Visit 15:
x
Record vital signs 
x
Measure weight
x
Conduct full neurologic examination
x
Administer C-SSRS (Since Last Visit version)
x
Serum pregnancy test (for female subjects of child-bearing potential)
x
Draw blood for laboratory safety assessment
x
Record concomitant medications
x
Perform drug accountability if tapered
x
Record AEs
No study drug will be dispensed.
9.1.16
Open-Label Extension Beyond Year One
Subjects who complete Visit 14 and will continue in the open-label treatment beyond year one will 
adhere to the following visit schedule. The investigator will schedule a return visit in 3 months. 
Subjects will have study visits every 3 months for a total of 4 visits per study year. The investigator
will perform some or all of the following assessments depending up on the visits.
Perform the following every 3 months from Visit 14
x
Record vital signs 
x
Conduct brief neurologic examination  if required
x
Administer C-SSRS (Since Last Visit version)
x
Perform urine pregnancy test (for female subjects of childbearing potential)

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x
Record concomitant medications
x
Perform drug accountability
x
Record AEs
x
Dispense open-label study drug bottles as instructed by IWRS
Perform the following every 6 months from Visit 14
x
Measure weight 
x
Draw blood for laboratory safety assessment
Perform the following every 12 months from Visit 14
x
Perform full physical exam
x
Perform 12-lead ECG once
x
Obtain urine for urinalysis 
This pattern will continue at the discretion of the investigator until development is stopped by SK 
Life Science Inc, the product is approved for marketing, or anytime at the discretion of SK Life 
Science Inc. 
After the first year of open-label treatment, the visits will be numbered sequentially beginning with 
Visit 16.
For subjects who discontinue any time after the first year of the open-label treatment, the subject 
should be brought to the clinic as soon as possible and the investigator will perform the assessments 
listed under Visit 14. The data collected at this visit will be entered in the Termination Visit page 
in eCRF. After this visit, the subject will be scheduled to return for Visit 15 (end-of-study follow-
up, 14 days after the last dose of study medication). 
9.2
Unscheduled Visit
At any time during the study, the subject may have an additional study visit/phone call if the 
investigator or the subject feels it is necessary. All information, including reason for visit/phone 
call, AEs, and any procedures performed should be collected in the source documents and recorded 
in the appropriate section of the eCRF.

9.3
Safety Assessments
Safety will be assessed by the nature, frequency, and severity of treatment-emergent spontaneously 
reported AEs, dropouts due to AEs, overall dropout rates, and changes from baseline in vital signs, 
physical and neurologic exams, clinical laboratory evaluations, 12-lead ECGs, and Columbia-
Suicide Severity Rating Scale (C-SSRS).
Study subjects will receive the following Hypersensitivity information on a laminated card to carry 
with them:    
x
Rash may occur and may progress to Drug Reaction with Eosinophilia and Systemic 
Symptoms (DRESS).
x
Rash or other signs or symptoms of hypersensitivity (e.g., fever, lymphadenopathy, and 
swelling) may herald a serious medical event and that the patient should report any such 
occurrence to the investigative site immediately.
x
Instructions on whom and where to call in the event a symptom arises and information that 
can be provided to an emergency room in the event the subject cannot reach the investigator 
site.
x
Reminder to check skin daily for evidence of rash for the first four months of therapy
If a subject reports a rash by telephone, an unscheduled visit should be performed promptly. Any 
patient with a rash or manifestation of hypersensitivity reaction such as lymphadenopathy, fever, 
facial swelling must be seen immediately at the study site. If it can definitely be determined that 
the rash or other symptoms are unrelated to study drug, then the subject can be maintained on 
YKP3809.  If the cause of the rash or other symptoms cannot be definitely determined 
immediately, then YKP3089 must be discontinued immediately. 
The initial physical/rash assessment for hypersensitivity reaction at the investigative site will 
include the following:
x
Measure body temperature

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9.4
Pharmacokinetic Evaluations
Time and date of each blood draw and dosing records (time/date/dose) of YKP3089 and AEDs 
prior to each blood draw will be recorded on the eCRF and other appropriate forms.
Plasma samples will be assayed for YKP3089 and AEDs at a specified bioanalytical laboratory 
using previously validated methods. Assay methodology will be detailed in separate assay 
protocols.
For subject taking phenytoin or phenobarbital
These samples will be obtained from subjects taking phenobarbital or phenytoin at any global sites.
At Visit 2, a single trough level of phenytoin or phenobarbital will be obtained. At Visits , 4, 5, 6, 
7 and 8, two blood samples will be collected for the determination of phenobarbital or phenytoin 
plasma levels: For the subjects taking phenytoin or phenobarbital in the morning and coming into 
the visits in the morning, the first blood draw will be collected upon subjects’ arrival to the study 
unit; the second blood draw should be collected within 30 minutes to 2 hours after the medication 
is taken. At Visits 8 and 9, two blood samples will be collected for YKP3089 depending on stability 
of dosing (stable dose all AEDs including YKP3089 for prior 2 weeks).                                                                
For subject taking concomitant AEDs other than phenytoin or phenobarbital
These samples will be obtained from subjects taking concomitant AEDs other than phenobarbital 
or phenytoin at US sites only.
At Visit 2, a single blood sample will be drawn to determine trough level if the subject is taking 
one of the followings, oxcarbazepine, topiramate, lamotrigine, lacosamide, clobazam, perampanel 
and levetiracetam. At Visit 8 and/or 9, two blood samples will be drawn from the same subjects to
determine plasma levels of YKP3089, oxcarbazepine, topiramate, lamotrigine, lacosamide, 
clobazam, perampanel and levetiracetam.  Collect at visit 8 and/ or 9 depending on stability of 
dosing (stable dose all AEDs including YKP3089 for prior 2 weeks). At Visit 8 and 9, for the 
subjects that are taking concomitant AEDs in the morning and coming into the visits in the 
morning, first blood draw will be collected upon subjects’ arrival to the study unit; the second 
blood draw should be collected within 30 minutes to 2 hours after the medication is taken. For 

patients that are taking concomitant AEDs in the afternoon and/or coming into the visits in the 
afternoon, the first blood draw will be collected upon subjects’ arrival to the study unit; the second 
blood draw should be collected within 30 minutes to 2 hours after the first blood draw with timing 
of the dose, blood draws and strength of previous dose clearly documented.
The collection schedule is summarized in Table 11 below.
Table 11. Blood Collection Schedule* for YKP3089 and AED Levels
Cohort Æ
Subjects taking Phenytoin or 
Phenobarbital
Subjects taking AEDs other 
than Phenytoin or 
Phenobarbital –US sites only
Blood collection for 
YKP3089 levels
Visits 8 and/or 9
Visits 8 and/or 9
Blood collection for 
phenytoin or phenobarbital 
levels
Visits 2*, 4, 5, 6, 7 and 8
Not Applicable
Blood collection for 
concomitant AEDs (other 
than phenytoin or 
phenobarbital) levels
None
Visits 2*, 8 and/or 9
* At Visit 2, one sample will be collected; at all other visits, two samples will be collected
Additional Samples
Additional blood samples may be drawn for levels of concomitant AEDs during the open label
maintenance phase if the investigator believes that symptoms of toxicity may be related to 
concomitant AEDs.
10 SAFETY AND ADVERSE EVENTS 
10.1
Definitions
10.1.1
Adverse Events
An adverse event (AE) is any symptom, sign, illness, or experience that develops or worsens in 
severity during the course of the study. Intercurrent illnesses or injuries should be regarded as AEs.
Abnormal results of diagnostic procedures are considered to be AEs if the abnormality:

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x
Results in study withdrawal
x
Is associated with an SAE
x
Is associated with clinical signs or symptoms
x
Leads to additional treatment or to further diagnostic tests
x
Is considered by the investigator to be of clinical significance
10.1.2
Serious Adverse Event
AEs are classified as serious or non-serious. A serious adverse event is any AE that is:
x
Fatal
x
Life-threatening
x
Requires or prolongs hospital stay
x
Results in persistent or significant disability or incapacity
x
A congenital anomaly or birth defect
x
An important medical event
Important medical events are those that may not be immediately life threatening but are clearly of 
major clinical significance. They may jeopardize the subject and may require intervention to 
prevent one of the other serious outcomes noted above. For example, drug overdose or abuse, a 
seizure that did not result in inpatient hospitalization, or intensive treatment of bronchospasm in 
an emergency department would typically be considered serious.
10.1.3
Suspected Adverse Reaction
Suspected adverse reaction means any AEs for which there is a reasonable possibility that the drug 
cause the AE. For the purpose of investigational new drug (IND) safety reporting, “reasonable
possibility” means there is evidence to suggest a causal relationship between the drug and AE.
Suspected adverse reaction implies a lesser degree of certainty about causality than adverse 
reaction, which means any AE caused by a drug. 
All AEs that do not meet any of the criteria for seriousness should be regarded as non-serious 
AEs.

10.1.4
Adverse Event Reporting Period
The study period during which AEs must be reported is normally defined as the period from the 
initiation of any study procedures (Visit 1) to the end of the study treatment follow-up. For this 
study, the AE reporting period is defined as 30 days following the last administration of study 
treatment for SAEs. For all other AEs, reporting period is defined as 14 days following the last 
administration of study treatment.
10.1.5
Preexisting Condition
A preexisting condition is one that is present at the start of the study. A preexisting condition 
should be recorded as an AE if the frequency, intensity, or the character of the condition worsens 
during the study period.
At Visit 1 any clinically significant abnormality should be recorded as a preexisting condition. At
the end of the study, any new clinically significant findings/abnormalities that meet the definition 
of an AE must also be recorded and documented as an AE.
Post-study Adverse Events
All unresolved AEs should be followed by the investigator until the events are resolved, the subject
is lost to follow-up, or the AE is otherwise explained. At the last scheduled visit, the investigator
should instruct each subject to report any subsequent event(s) that the subject, or the subject’s 
personal physician, believes might reasonably be related to participation in this study.
The investigator should notify the study Sponsor of any death or AE occurring at any time after a 
subject has discontinued or terminated study participation that may reasonably be related to this 
study. The Sponsor should also be notified if the investigator should become aware of the 
development of cancer or of a congenital anomaly in a subsequently conceived offspring of a 
subject who has participated in this study.
Abnormal Laboratory Values
A clinical laboratory abnormality should be documented as an AE if any one of the following
conditions is met:

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x
The laboratory abnormality is not otherwise refuted by a repeat test to confirm the abnormality.
x
The abnormality suggests a disease and/or organ toxicity.
x
The abnormality is of a degree that requires active management (eg, change of dose, 
discontinuation of the drug, more frequent follow-up assessments, further diagnostic 
investigation).
Hospitalization, Prolonged Hospitalization, or Surgery
Any AE that results in hospitalization or prolonged hospitalization should be documented and 
reported as a serious AE unless specifically instructed otherwise in this protocol. Any condition 
responsible for surgery should be documented as an AE if the condition meets the criteria for an 
AE.
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an 
AE in the following circumstances:
x
Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for 
a preexisting condition. Surgery should not be reported as an outcome of an AE if the purpose 
of the surgery was elective or diagnostic and the outcome was uneventful.
x
Hospitalization or prolonged hospitalization required to allow efficacy measurement for the 
study.
x
Hospitalization or prolonged hospitalization for therapy of the target disease of the study, 
unless it is a worsening or increase in frequency of hospital admissions as judged by the clinical 
investigator.
x
An Emergency Room visit is not considered hospitalization.
10.2
Adverse Event Recording and Assessing
All AEs occurring during this clinical trial will be recorded. The investigator will review each 
event and assess its relationship to drug treatment (unrelated, remote, possible, probable, or
definite). Each sign or symptom reported will be graded on a 3-point severity scale (mild, 
moderate, or severe), and the date of onset, time of onset, and outcome of each event will be noted.
The relationship of each AE to study drug will be assessed using the following definitions:

Definite
x
Distinct temporal relationship with drug treatment
x
Known reaction to agent or chemical group, or predicted by known 
pharmacology
x
Event cannot be explained by subject’s clinical state or other factors
Probable
x
Reasonable temporal relationship with drug treatment
x
Likely to be known reaction to agent or chemical group, or predicted by 
known pharmacology
x
Event cannot easily be explained by subject’s clinical state or other factors
Possible
x
Reasonable temporal relationship with drug treatment
x
Event could be explained by subject’s clinical state or other factors
Remote
x
Poor temporal relationship with drug treatment
x
Event easily explained by subject’s clinical state or other factors
Unrelated
x
Event occurring before dosing
x
Event or intercurrent illness due wholly to factors other than drug treatment
The following definitions for rating severity will be used:
x
Mild: The AE is easily tolerated and does not interfere with daily activity.
x
Moderate: The AE interferes with daily activity, but the subject is still able to function.
x
Severe: The AE is incapacitating and requires medical intervention.
10.3
Reporting of Adverse Events
At each contact with the subject, the investigator must seek information on AEs by specific 
questioning and, as appropriate, by examination. Information on all AEs should be recorded 
immediately in the source document and also in the appropriate AE module of the eCRF. All
clearly related signs, symptoms, and abnormal diagnostic procedures results should recorded in 
the source document, though they should be grouped under one diagnosis.

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All AEs occurring during the study period must be recorded on the appropriate eCRFs. The clinical 
course of each event should be followed until resolution, stabilization, or until it has been 
determined that the study treatment or participation is not the cause. Serious AEs that are still 
ongoing at the end of the study period must be followed up to determine the final outcome. Any 
serious AE that occurs after the study period and is considered to be possibly related to the study 
treatment or study participation should be recorded and reported immediately no later than 24 
hours after awareness of the event.
10.3.1
Study Sponsor Notification by Investigator
In the event of any fatal or life-threatening SAE, the investigator must inform SK Life Science, 
Inc. (SKLSI) designee QDS by telephone immediately.  Any non-fatal or non-life-threatening 
SAE, regardless of expectedness or causality, must be reported on the SAE Report Form by 
scanned and emailed to SKLSI’s designee QDS within 24 hours of the investigator’s or any other 
study center personnel’s knowledge of the event as described below. 
A completed SAE Report Form, the AE record, pertinent medical records, and the Concurrent 
Medication record from the source documents should be scanned and emailed to SKLSI’s 
designee QDS within 24 hours of the investigator’s or any study center personnel’s knowledge of 
a serious event.  An updated SAE Report Form should be forwarded to SKLSI’s designee QDS 
within 24 hours of receipt of new/updated information.  The SAE Reporting Requirements and 
contact information are outlined in Table 12.
Seizures in this subject population are anticipated.  Therefore, seizures, in and of themselves, will 
not be considered adverse events.  Seizures to be considered adverse events will include those 
occurring with a measurable increase over the subject’s typical seizure frequency or duration; or 
multiple seizures in a pattern distinguishable from the usual seizure pattern. 
Table 12. Serious Adverse Event Reporting Requirements
Type of SAE
Reporting
Reporting
Email address, Telephone Number,

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x
Study center
x
Subject number
x
A description of the event
x
Date of onset
x
Current status 
x
Whether study treatment was discontinued
x
The reason why the event is classified as serious
x
Investigator assessment of the association between the event and study treatment
Within the following 48 hours, the investigator must provide further information on the serious 
AE in the form of a written narrative. This should include a copy of the completed SAE form, and 
any other diagnostic information that will assist the understanding of the event. Significant new 
information on ongoing serious AEs should be provided promptly to the study Sponsor.
10.3.2
Ethics Committee/Institutional Review Board Notification by Investigator
Reports of all serious AEs (including follow-up information) must promptly be submitted to the 
Ethics Committee/Institutional Review Board (EC/IRB). Copies of each report and documentation 
of EC/IRB notification and receipt will be kept in the clinical investigator’s binder.
10.3.3
Regulatory Authority Notification of IND Safety Reports by Sponsor
The study Sponsor must notify the FDA and all participating investigators in an IND safety report 
of potential serious risks from clinical trials as soon as possible but in no case later than 15 calendar 
days after the Sponsor determines that the information qualifies for reporting. This includes any 
suspected adverse reaction that is both serious and unexpected (SUSAR).
The study Sponsor must notify the FDA of any unexpected fatal or life-threatening suspected 
adverse reaction as soon as possible but no later than 7 calendar days from the Sponsor’s initial 
receipt of the information.
If a previous AE that was not initially deemed reportable is later found to fit the criteria for 
reporting, the study Sponsor will submit the AE in a written report to the FDA as soon as possible, 
but no later than 15 calendar days from the time the determination is made.

The notification of other Regulatory Authorities follows the same procedure and timeframe, per 
ICH Guidance, as for the FDA.
10.4
Withdrawal of Subject from Study 
Subjects may be withdrawn from the study prior to completion of the study if:
x
Consent is withdrawn by the subject
x
The subject fails to adhere to the protocol requirements
x
An intolerable AE is experienced
x
The subject becomes pregnant
x
The subject is lost to follow-up
When a subject is withdrawn, the discharge procedures must be performed. The reason(s) for the 
withdrawal must be documented in the subject’s eCRF.
11 DATA HANDLING PROCEDURES
11.1
Data Handling and Record Keeping 
11.1.1
Confidentiality
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act (HIPAA). Those 
regulations require a signed subject authorization informing the subject of the following:
x
What protected health information (PHI) will be collected from subjects in this study
x
Who will have access to that information and why
x
Who will use or disclose that information
x
The rights of a research subject to revoke their authorization for use of their PHI
The subjects will be told that representatives of the Sponsor, IRB/IEC, or regulatory authorities 
may inspect their medical records to verify the information collected and that all personal 
information made available for inspection will be handled in strictest confidence and in accordance 
with local data protection laws.

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In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject
authorization. For subjects who have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect at least vital status (ie, that the subject is alive) at the end 
of his or her scheduled study period.
11.1.2
Source Documents
Source data is all information, original records of clinical findings, observations, or other activities 
in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are 
contained in source documents. Examples of these original documents and data records include 
hospital records; clinical and office charts; laboratory notes; memoranda; subjects’ diaries or 
evaluation checklists; pharmacy dispensing records; recorded data from automated instruments;
copies or transcriptions certified after verification as being accurate and complete; microfiches;
photographic negatives; microfilm or magnetic media; x-rays; subject files; and records kept at the 
pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial.
11.1.3
Electronic Case Report Forms
The eCRF is the primary data collection instrument for the study. All data requested on the eCRF 
must be recorded. All missing data must be explained. Details of the completion of the eCRF will 
be included in a data entry manual.
11.1.4
Records Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRFs 
and all source documents that support the data collected from each subject, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical 
Trial, and all study documents as specified by the applicable regulatory requirement(s).
The investigator/institution will take measures to prevent accidental or premature destruction of 
these documents. Essential documents must be retained 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 until at least 2 years have elapsed since the formal 

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12 STATISTICAL METHODS AND PLANNED ANALYSES
12.1
Statistical Methods
Categorical variables will be summarized as frequencies and percentages. Descriptive statistics for 
continuous variables will include number of subjects, mean, median, standard deviation, and 
minimum and maximum values. SAS® version 9.2 or later will be used for all data summaries.
Data will be used as collected.  
12.2
Analysis Data Sets
Enrolled subjects: All subjects who successfully meet their entry criteria and who have given 
informed consent to participate in this study will be considered enrolled subjects.
Safety evaluable subjects (SE): All subjects enrolled in the study who received at least one dose of 
study drug medication will be considered safety evaluable subjects. 
Three safety evaluable subgroups of subjects will be defined: 
o
Subjects taking phenytoin and YKP3089
o
Subjects taking Phenobarbital and YKP3089
o
Subjects taking concomitant AEDs other than phenytoin or Phenobarbital and 
YKP3089
12.3
Baseline Characteristics
All demographic measurements (age, gender, race, ethnicity, height, and weight) and all baseline 
safety measurements (medical and seizure history, MRI, CAT, ECGs, vital signs, clinical 
laboratory values, physical and brief neurologic exam, and C-SSRS) will be summarized for all 
enrolled subjects, for all safety evaluable subjects and by the 3 subgroups of subjects defined in 
Section 12.2.

12.4
Safety Variable Analyses
All enrolled subjects who took at least one dose of study drug medication will be evaluable for 
safety. The number and percent of subjects reporting AEs (including treatment-emergent 
laboratory abnormalities) will be tabulated for all safety evaluable subjects and by the 3 subgroups 
of subjects defined in Section 12.2. All serious AEs (SAEs) will be tabulated separately as well as 
included with all reported AEs. 
Physical and neurologic assessments, laboratory results, vital signs (including orthostatic 
measurements, weight and height), concomitant medications, ECGs, and C-SSRS will be 
summarized using descriptive statistics.
Extent of exposure and dose modifications will be tabulated.
12.5
Pharmacokinetics and Pharmacodynamics Analysis
YKP3089 plasma concentration data collected from this study will be pooled with data from other 
YKP3089 clinical trials for possible population pharmacokinetic and pharmacodynamic analysis. 
An integrated population pharmacokinetic model for YKP3089 will be developed. Standard 
population pharmacokinetic parameters (eg, total body clearance, CL/F) in epilepsy patients and 
their inter- and intra-individual variability will be estimated. The effects of demographic 
characteristics, concomitant medication including AEDs, laboratory values, and other subject 
covariates on YKP3089 pharmacokinetics will be evaluated. 
For phenytoin, phenobarbital plasma concentrations obtained during titration phase (Visits 3-6)
will be compared with that taken at baseline (Visit 2) to assess the effect of YKP3089 on these two 
AEDs. The timing of AED sampling in relation to the subject’s AED dosing schedule will be 
factored into the analysis.
For each concomitant AED (oxcarbazepine, topiramate, lamotrigine, lacosamide, clobazam, 
perampanel and levetiracetam only), plasma concentrations obtained at Visits 8 and or 9 will be 
compared with that taken at baseline (Visit 2) to assess the effect of YKP3089 on these 7 AEDs. 
The timing of AED sampling in relation to the subject’s AED dosing schedule will be factored 
into the analysis. 

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If warranted, the AED plasma concentration data collected from this study will be pooled with 
data from other YKP3089 studies to assess the potential for an interaction with YKP3089. Results 
will be displayed descriptively in tabular form.
13 LEGAL ASPECTS, ETHICAL AND ADMINISTRATIVE ISSUES 
13.1
Good Clinical Practice
This study is to be conducted according to US and international standards of GCP (FDA Title 21
parts 50 and 312 and ICH guidelines), applicable government regulations, and institutional 
research policies and procedures. This protocol and any amendments will be submitted to a 
properly constituted independent EC/IRB, in agreement with local legal prescriptions, for formal 
approval of the study conduct. The decision of the EC/IRB concerning the conduct of the study 
will be made in writing to the investigator and a copy of this decision will be provided to the 
Sponsor before commencement of this study. The investigator should provide a list of EC/IRB 
members and their affiliate to the Sponsor.
13.2
Documentation of Consent
Written consent of a subject, using the EC/IRB-approved consent form, will be obtained before 
that subject undergoes any study procedure. The individual who consents the subject must be listed 
on the delegation log and be authorized to obtain consent. All subjects will have adequate time to 
ask questions and will be provided with a signed copy of the consent for his/her records. The 
consenting process will be clearly documented in the subject’s chart. The principal investigator is 
responsible for ensuring that valid consent is obtained and documented for all subjects.
13.3
Delegation of Investigator Responsibilities
The qualified investigator will ensure that all persons assisting the trial are adequately qualified, 
informed about the protocol, any amendments to the protocol, the study treatments, and their trial-
related duties and functions. The qualified investigator will maintain a list of sub-investigators and 
other appropriately qualified persons to whom he delegates significant trial-related duties.

13.4
Conflict of Interest
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or 
financial gain greater than the minimum allowable by their institution, etc.) must have the conflict 
reviewed by a properly constituted Conflict of Interest Committee with a Committee-sanctioned 
conflict management plan that has been reviewed and approved by the study Sponsor prior to 
participation in this study.
13.5
Publication Plan
Neither the complete nor any part of the results of the study carried out under this protocol, nor 
any of the information provided by the Sponsor for the purposes of performing the study, will be 
published or passed on to any third party without the consent of the study Sponsor. Any 
investigator involved with this study is obligated to provide the Sponsor with complete test results 
and all data derived from the study.
13.6
Protocol Amendments
Protocol Amendments will not be implemented without agreement from the Sponsor and prior 
submission to and written approval from the EC/IRB, except when necessary to eliminate an 
immediate hazard to the subject. 
13.7
Study Monitoring, Auditing, and Inspecting
13.7.1
Study Monitoring Plan
This study will be monitored according to the monitoring plan and in accordance with 21 CFR 
312.53(d) and ICH guidelines. The investigator will allocate adequate time for such monitoring 
activities. The investigator will also ensure that the monitor or other compliance or quality 
assurance reviewer is given access to all the above noted study-related documents and study related 
facilities (eg, pharmacy, diagnostic laboratory), and has adequate space to conduct the monitoring 
visit.

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13.7.2
Auditing and Inspecting
The investigator will permit study-related monitoring, audits, and inspections by the EC/IRB, the 
Sponsor, government regulatory bodies, and University compliance and quality assurance groups 
of all study related documents (eg, source documents, regulatory documents, data collection 
instruments, study data). The investigator will ensure the capability for inspections of applicable 
study-related facilities (eg, pharmacy, diagnostic laboratory).
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable University compliance and quality assurance 
offices.

APPENDIX A: FULL PHYSICAL EXAMINATION
FULL PHYSICAL EXAMINATION
BODY SYSTEM
Normal
Abnormal, 
NCS 
Abnormal, 
CS 
Not Done
If Abnormal, Specify Findings
General Appearance




Head




EENT




Neck




Cardiovascular




Abdominal




Respiratory




Musculoskeletal




Extremities




Neurological




Skin




Other, specify:
________________




Other, specify:
________________





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APPENDIX B: FULL NEUROLOGIC EXAMINATION
FULL NEUROLOGIC EXAMINATION
GENERAL
Normal
Abnormal, 
NCS
Abnormal, 
CS
Not Done
If Abnormal,
Specify Findings – including 
laterality, as applicable
1. Level of Consciousness




2. Mental Status




3. Visual Fields (II)




4. Eye Movements (III, IV, VI)




5. Jaw Movement and Facial Sensation (V)




6. Facial Motion (VII)




7. Hearing (VIII)




8. Swallowing, pharynx, larynx (IX, X)




9. SCM, trapezius (XI)




10. Tongue (XII)




11. Biceps Reflexes




12. Triceps Reflexes




13. Patellar Reflexes




14. Achilles Reflexes




15. Plantar Reflexes




16. Gait




17. Romberg




18. Nystagmus




19. Tremor




20. Finger-Nose




21. Heel-Shin




22. Rapid Alternating Movements




23. Muscle Strength




24. Pin




25. Vibration





APPENDIX C: BRIEF NEUROLOGIC EXAMINATION
BRIEF NEUROLOGIC EXAMINATION
GENERAL
Normal
Abnormal, 
NCS
Abnormal, 
CS
Not Done
If Abnormal,
Specify Findings – including 
laterality, as applicable
1. Level of consciousness




2. Mental status




3. Biceps reflexes




4. Knee reflexes




5. General movement




6. Gait




7. Romberg




8. Nystagmus




9. Tremor




10. Finger-nose




11. Heel-shin




12. Rapid alternating movements





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APPENDIX D: COLUMBIA SUICIDE SEVERITY RATING SCALE (BASELINE/SCREENING)

APPENDIX E: COLUMBIA SUICIDE SEVERITY RATING SCALE (SINCE LAST VISIT)

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14 REFERENCES
1. World Health Organization. Epilepsy: Aetiogy, epidemiology and prognosis. WHO Fact Sheet 
No. 165, February 2001.
2. Guidelines for the clinical evaluation of antiepileptic drugs. Epilepsia 1989;30:400-406.
3. European Agency for the Evaluation of Medicinal Products, Committee for Proprietary 
Medicinal Products. Note for guidance on clinical investigation of medicinal products in the 
treatment of epileptic disorders. CPMP/EWP/566/98 rev 1, 2000.
4. Food and Drug Administration, Guidelines for the clinical evaluation of antiepileptic drugs 
(adults and children). HHS (FDA) 81-3110, 1981.