Clinical trial NCT03976076
Conditions: Refractory Infantile Spasms
Keywords: JBPOS0101 Infantile Spasms Electroencephalogram
Sponsor: Bio-Pharm Solutions Co., Ltd.
Start date: 2020-04-15; Completion date: 2021-12-10
Enrollment: 16 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A Phase 2 Study to Assess the Safety, Tolerability, Exploratory Efficacy, and pharmacokinetics of Orally Administered JBPOS0101 for Refractory Infantile Spasms Patients.

Detailed description:
This open label, multicenter study allowed JBPOS0101 (investigational product) to be given as either add-on therapy or monotherapy for patients with refractory infantile spasms. The design and choice of study population of this Phase 2 clinical study was based on the need to provide initial safety, tolerability, pharmacokinetics (PK), and efficacy outcomes of the investigational product for future clinical studies.

Arms: arm 1: During Treatment Period 1, the IP was administered at 6 mg/kg, per oral (PO), twice a day (BID), once in the morning and 12 hours following the morning dose during the first 7 days of Treatment Period 1. Starting from the PM dose on Visit 3, the dose was escalated and patients received the Investigational Product (JBPOS0101) (IP) at a dose of 9 mg/kg orally BID. Starting on Day 15, the dose was escalated again and patients received the IP at a dose of 15 mg/kg orally BID until the end of Treatment Period 1 (Day 28). Each dose of the IP was administered after at least a 2-hour fast. Food was given 2 hours after dosing.
Interventions: intervention 1: JBPOS0101
Intervention descriptions: intervention 1: JBPOS0101 (investigational product)

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
IND 134128 
 
A Phase 2 Study to Assess the Safety, Tolerability, Exploratory Efficacy, 
and Pharmacokinetics of Orally Administered JBPOS0101 for Refractory 
Infantile Spasms Patients 
 
PROTOCOL NO.: CL-0101-WS01 
Sponsor: 
Bio-Pharm Solutions Co., Ltd. 
6F, C Bldg., Advanced Institute of Convergence 
Technology 
145 Gwanggyo-Ro, Yeongtong-Gu Suwon, Gyeonggi-Do 
Korea 16229 
Sponsor Contact: 
 
Version of Protocol:  
2.0 
Date of Protocol:  
15 September 2020 
 
CONFIDENTIAL 
All financial and nonfinancial support for this study will be provided by Bio-Pharm Solutions 
Co., Ltd. The concepts and information contained in this document or generated during the 
study are considered proprietary and may not be disclosed in whole or in part without the 
expressed, written consent of Bio-Pharm Solutions Co., Ltd. 
The study will be conducted according to the International Council for Harmonisation 
harmonised tripartite guideline E6(R2): Good Clinical Practice. 
 


Bio-Pharm Solutions Co., Ltd. 
Protocol: Version 2.0 
Protocol Approval - Sponsor Signatory 
CL-0101-WSOI 
15 September 2020 
Study Title 
A Phase 2 Study to Assess the Safety, Tolerability, Exploratory 
Efficacy, and Pharmacokinetics of Orally Administered JBPOSO 101 
for Refractory Infantile Spasms Patients. 
Protocol Number CL-0101-WSOl 
Protocol Date 
Protocol Version 2.0 - 15 September 2020 
Protocol accepted and approved by: 
President and CEO 
Dr. Yong Moon Choi, Ph.D. 
Bio-Phann Solutions Co., Ltd. 
6F, C Bldg., Advanced Institute of Convergence Technology 
145 Gwanggyo-Ro, Yeongtong-Gu Suwon, Gyeonggi-Do 
Korea 16229 
Page 2


Bio-Pharm Solutions Co., Ltd. 
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Declaration of Investigator 
I have read and understood all sections of the protocol entitled “A Phase 2 Study to Assess 
the Safety, Tolerability, Exploratory Efficacy, and Pharmacokinetics of Orally Administered 
JBPOS0101 for Refractory Infantile Spasms Patients” and the accompanying current version 
of the investigator’s brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the Final Protocol Version 2.0, dated 15 September 2020, the International 
Council for Harmonisation harmonised tripartite guideline E6(R2): Good Clinical Practice 
and all applicable government regulations. I will not make changes to the protocol before 
consulting with Bio-Pharm Solutions Co., Ltd. or implement protocol changes without 
institutional review board (IRB) approval except to eliminate an immediate risk to patients. I 
agree to administer study treatment only to patients under my personal supervision or the 
supervision of a subinvestigator. 
I will not supply the investigational drug to any person not authorized to receive it. 
Confidentiality will be protected. Patient identity will not be disclosed to third parties or 
appear in any study reports or publications. 
I will not disclose information regarding this clinical investigation or publish results of the 
investigation without authorization from Bio-Pharm Solutions Co., Ltd. 
Signature of Principal Investigator 
Date 
Printed Name of Principal Investigator 
Page 3


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Table of Contents 
Table of Contents .......................................................................................................................4 
List of Tables ..............................................................................................................................7 
List of Figures ............................................................................................................................7 
Protocol Synopsis.......................................................................................................................8 
List of Abbreviations................................................................................................................14 
1 
Introduction ......................................................................................................................16 
1.1 
Overview of Infantile Spasms .................................................................................16 
1.2 
Approved Indications and Unmet Medical Need....................................................16 
1.3 
Rationale for Using JBPOS0101 (Investigational Product) for Treatment of 
Infantile Spasms ..............................................................................................17 
1.4 
Summary of Nonclinical and Clinical studies ........................................................18 
1.4.1 
Nonclinical Summary ..............................................................................18 
1.4.2 
Clinical Summary ....................................................................................20 
1.4.3 
Clinical versus Preclinical .......................................................................21 
2 
Study Objectives...............................................................................................................22 
2.1 
Primary Objective ...................................................................................................22 
2.2 
Secondary Objective ...............................................................................................22 
2.3 
Exploratory Objective .............................................................................................22 
3 
Investigational Plan ..........................................................................................................23 
3.1 
Study Design ...........................................................................................................23 
3.1.1 
Rationale of Study Design .......................................................................27 
4 
Patient Selection and Withdrawal Criteria .......................................................................28 
4.1 
Selection of Study Population .................................................................................28 
4.1.1 
Inclusion Criteria .....................................................................................28 
4.1.2 
Exclusion Criteria ....................................................................................29 
4.2 
Withdrawal of Patients From the Study ..................................................................30 
4.2.1 
Reasons for Withdrawal/Discontinuation ................................................30 
4.2.2 
Handling of Withdrawals .........................................................................31 
4.2.3 
Replacements ...........................................................................................32 


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5 
Study Treatments ..............................................................................................................33 
5.1 
Treatments Administered ........................................................................................33 
5.2 
Identity of Investigational Product..........................................................................33 
5.3 
Management of Clinical Supplies ...........................................................................34 
5.3.1 
Investigational Product Packaging and Storage.......................................34 
5.3.2 
Investigational Product Accountability ....................................................34 
5.4 
Overdose Management ...........................................................................................35 
5.4.1 
Treatment of Overdose ............................................................................35 
5.5 
Blinding ..................................................................................................................35 
5.6 
Treatment Compliance ............................................................................................35 
5.7 
Prior and Concomitant Medication .........................................................................35 
6 
Study Assessments and Procedures ..................................................................................37 
6.1 
Safety and Tolerability Assessments .......................................................................37 
6.1.1 
Physical and Neurological Examination ..................................................37 
6.1.2 
Vital Sign Measurements, Height, Weight, and Body Mass Index ..........37 
6.1.3 
Electrocardiograms ..................................................................................38 
6.1.4 
Clinical Laboratory Tests .........................................................................38 
6.1.5 
Adverse Events ........................................................................................40 
6.1.5.1 
Definitions of Adverse Events .................................................................40 
6.1.5.2 
Serious Adverse Events ...........................................................................40 
6.1.5.3 
Eliciting and Documenting Adverse Events ............................................41 
6.1.5.4 
Reporting Adverse Events .......................................................................41 
6.1.5.5 
Reporting Serious Adverse Events ..........................................................42 
6.1.5.6 
Assessment of Severity ............................................................................42 
6.1.5.7 
Assessment of Causality ..........................................................................42 
6.1.5.8 
Follow-up of Patients Reporting Adverse Events ....................................43 
6.2 
Pharmacokinetic Assessments ................................................................................43 
6.2.1 
Pharmacokinetic Blood and Urine Samples ............................................43 
6.2.2 
Pharmacokinetic Parameters ....................................................................44 
6.3 
Exploratory Efficacy Assessments ..........................................................................44 
6.3.1 
Electroencephalogram .............................................................................44 
6.3.2 
Seizure Diary ...........................................................................................44 
6.3.3 
Clinical Global Impression of Change ....................................................45 


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6.4 
Safety Monitoring Committee ................................................................................45 
6.5 
Sample Collections .................................................................................................46 
6.6 
Unscheduled Visits ..................................................................................................46 
7 
Statistical and Analytical Plan ..........................................................................................47 
7.1 
Primary Safety Endpoints .......................................................................................47 
7.2 
Pharmacokinetic Endpoints ....................................................................................47 
7.3 
Exploratory Efficacy Endpoints ..............................................................................47 
7.4 
Sample Size Calculations ........................................................................................48 
7.5 
Analysis Sets ...........................................................................................................49 
7.6 
Description of Subgroups to Be Analyzed ..............................................................49 
7.7 
Statistical Analysis Methodology ...........................................................................50 
7.7.1 
Analysis of Primary Safety Endpoint ......................................................50 
7.7.2 
Pharmacokinetic Analyses .......................................................................51 
7.7.3 
Analysis of Exploratory Efficacy Endpoints ...........................................52 
7.7.4 
Interim Analyses ......................................................................................52 
8 
Data Quality Assurance ....................................................................................................53 
8.1 
Data Management ...................................................................................................53 
9 
Ethics ................................................................................................................................55 
9.1 
Institutional Review Board .....................................................................................55 
9.2 
Ethical Conduct of the Study ..................................................................................55 
9.3 
Patient Information and Consent ............................................................................55 
10 Investigator’s Obligations ................................................................................................57 
10.1 Confidentiality ........................................................................................................57 
10.2 Financial Disclosure and Obligations .....................................................................57 
10.3 Investigator Documentation ....................................................................................58 
10.4 Study Conduct .........................................................................................................58 
10.5 Adherence to Protocol ............................................................................................58 
10.6 Adverse Events and Study Report Requirements ...................................................59 
10.7 Investigator’s Final Report .....................................................................................59 
10.8 Records Retention ...................................................................................................59 


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10.9 Publications .............................................................................................................59 
11 Study Management ...........................................................................................................60 
11.1 Monitoring ..............................................................................................................60 
11.1.1 
External Data Monitoring Committee .....................................................60 
11.1.2 
Monitoring of the Study ...........................................................................60 
11.1.3 
Inspection of Records ..............................................................................60 
11.2 Management of Protocol Amendments and Deviations..........................................61 
11.2.1 
Modification of the Protocol ....................................................................61 
11.2.2 
Protocol Deviations .................................................................................61 
11.3 Study Termination ...................................................................................................61 
11.4 Final Report ............................................................................................................62 
12 Reference List...................................................................................................................63 
13 Appendices .......................................................................................................................64 
13.1 Appendix: Schedule of Events ................................................................................64 
13.2 Appendix: Pharmacokinetic Sampling ...................................................................67 
13.3 Appendix: List of Excluded Medications ...............................................................68 
13.4 Appendix: Summary of Changes to Protocol CL-0101-WS01...............................73 
13.4.1 
Regulatory History and Overview ...........................................................74 
13.4.2 
Summary of Changes ...............................................................................75 
 
List of Tables 
Table 6–1 
Clinical Global Impression of Change Scale .................................................. 45 
Table 13–1 
Schedule of Events .......................................................................................... 64 
Table 13–2 
Steady State Pharmacokinetic Sampling Time Points .................................... 67 
Table 13-3: 
Summary of Protocol CL-0101-WS01 Revision History ............................... 74 
 
List of Figures 
Figure 3-1 
Study Design ................................................................................................... 27 


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Protocol Synopsis 
Protocol Number: 
CL-0101-WS01 
Title: 
A Phase 2 Study to Assess the Safety, Tolerability, Exploratory 
Efficacy, and Pharmacokinetics of Orally Administered 
JBPOS0101 for Refractory Infantile Spasms Patients 
Sponsor: 
Bio-Pharm Solutions Co., Ltd. 
Study Phase: 
Phase 2 
Study Sites: 
Multicenter study 
Indication: 
Infantile spasms (IS) 
Rationale: 
This open-label, multicenter study design allows JBPOS0101 
(investigational product) to be given as either add-on therapy or 
monotherapy for patients with refractory infantile spasms. The 
design and choice of study population of this Phase 2 clinical 
study is based on the need to provide initial safety, tolerability, 
pharmacokinetics (PK), and efficacy outcomes of the 
investigational product for future clinical studies. 
Objectives: 
Primary Objective 
To evaluate the safety and tolerability of the investigational 
product in patients with refractory IS. 
Secondary Objective 
To characterize the PK of the investigational product in patients 
with refractory IS. 
Exploratory Objective 
To evaluate the efficacy of the investigational product in treating 
patients with refractory IS. 
Study Population: 
Inclusion criteria 
Male or female between 6 months through 36 months of age at 
the time of informed consent, has clinical diagnosis of IS, 
confirmed by video-electroencephalogram (EEG) analysis, and 
hypsarrhythmia on EEG at screening according to the Burden of 
Amplitudes and Epileptiform Discharges (BASED) scale score. 
As assessed by the investigator has no or partial response to at 
least 2 out of the 3 therapies of adrenocorticotrophic hormone 
(ACTH), vigabatrin, and glucocorticoids (i.e. prednisolone), or 
has no or partial response to at least 1 out of the 3 therapies of 
ACTH, vigabatrin, and glucocorticoids and is contraindicated to 
and/or refused by the patient’s legal representative(s) for 
treatment with one or both other 2 therapies. Patients has general 
good health (defined as the absence of any clinically relevant 


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abnormalities as determined by the investigator) based on 
physical and neurological examinations, medical history, normal 
renal function and electrocardiogram (ECG), and clinical 
laboratory values completed during the Screening Period visit 
(Visit 1). 
Exclusion criteria 
Patient considered by the investigator, for any reason (including, 
but not limited to, the risks described as precautions and 
warnings in the current version of the investigator’s brochure for 
investigational product) to be an unsuitable candidate to receive 
the investigational product. 
Patient has known or suspected allergy to the investigational 
product or apple juice. 
Patient has clinically significant renal impairment, defined as 
creatinine >1.5 mg/dL or blood urea nitrogen >2 × upper limit of 
normal (ULN); clinically significant liver dysfunction, defined 
as total bilirubin ≥2 × ULN, or aspartate aminotransferase or 
alanine aminotransferase ≥3 × ULN; has clinically significant 
abnormal laboratory values; the investigator may deem the 
patient eligible if he/she judges the laboratory values to be not 
clinically significant. 
Patient has an ongoing or known history of human 
immunodeficiency virus infection, or chronic hepatitis B or C. 
Patient has a clinically significant abnormality on ECG that, in 
the opinion of the investigator, increases the safety risks of 
participating in the study. 
Patient has a neurodegenerative disorder as the underlying cause 
of IS. 
Patient has a known history of aspiration pneumonia within the 
past year. 
Patient has previously participated in another clinical study of 
the investigational product or received any investigational drug 
or device or investigational therapy within 30 days of study 
entry. 
Patient has received therapy with felbamate, cannabinoids, 
ketogenic diet or vagus nerve stimulation within 14 days of 
screening. 
Patient has received therapy with a medication known to be a 
CYP3A4 substrate and whose PK has been shown to be 
impacted in the presence of a CYP3A4 inhibitor within 14 days 


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of screening (see Appendix 13.3 for a non-exhaustive list of 
CYP3A4 substrates). 
Patient has not remained at stables doses of all drugs used for 
treating epileptic seizures for at least 14 days prior to screening 
(except for rescue medications used for acute treatment of 
breakthrough seizures which are not known to be CYP3A4 
substrates and whose PK has not been shown to be impacted in 
the presence of a CYP3A4 inhibitor [see Appendix 13.3 for a 
non-exhaustive list of CYP3A4 substrates]). 
Patient has a lethal or potentially lethal condition other than 
infantile spasms, with a significant risk of death before 18 
months of age such as non-ketotic hyperglycinemia. 
Patient has an underlying metabolic disease associated with 
glucose intolerance (e.g., glucose transporter deficiencies). 
Patient has a body weight below 5 kg. 
Study Design: 
This is an open-label, multicenter study to evaluate the safety, 
tolerability, PK, and exploratory efficacy of the investigational 
product in children aged 6 months through 36 months with IS. 
Patients will receive the investigational product at a dose of 
6 mg/kg orally twice daily; once in the morning and 12 hours 
following the morning dose during the first 7 days of Treatment 
Period 1. Starting from the PM dose on the day of Visit 3, the 
dose will be escalated and patients will receive the 
investigational product at a dose of 9 mg/kg orally twice daily. 
Starting on Day 15, the dose will be escalated again and patients 
will receive the investigational product at a dose of 15 mg/kg 
orally twice daily until the end of Treatment Period 1. 


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Estimated Study 
Duration: 
The overall study duration is expected to be up to 84 days 
(± 5 days). The study is planned to include 4 periods: Screening 
Period (up to 28 days), Treatment Period 1 (28 days), Treatment 
Period 2 (Dose Tapering Period [14 days]), and a Follow-Up 
Period (14 days). 
The actual length of the Screening Period is expected to be 
appreciably shorter than 28 days as patients who meet study 
entry criteria will be eligible to receive the investigational 
product on the 6th day after completing all screening procedures 
and assessments. 
During the Screening Period, Treatment Period 1, and Treatment 
Period 2, no changes to dosages of any drugs used for treating 
epileptic seizures will be permitted (except for rescue 
medications used for acute treatment of breakthrough seizures 
which are not known to be CYP3A4 substrates and whose PK 
has not been shown to be impacted in the presence of a CYP3A4 
inhibitor [see Appendix 13.3 for a non-exhaustive list of 
CYP3A4 substrates]). Changes of dosages of drugs used for 
treating epileptic seizures will be permitted 2 or more days after 
the investigational product has been discontinued. 
Safety Assessments: 
Safety assessments include monitoring and reporting of adverse 
events related to physical and neurological examination findings, 
vital sign measurements (blood pressure, pulse, and respiratory 
rate), height, weight, body mass index, ECG tracings, and 
clinical laboratory test results (hematology, serum chemistry, 
and urinalysis). 
Pharmacokinetic 
Assessments: 
Plasma concentration of the investigational product will be 
measured. Population PK analysis will be performed to calculate 
plasma PK parameters for the investigational product. The 
primary plasma PK parameters for the investigational product 
will include the area under the concentration-time curve (AUC), 
minimum plasma concentration (Cmin), and maximum plasma 
concentration (Cmax). Other PK parameters may be calculated, as 
appropriate. 
Efficacy Assessments: 
Efficacy assessment will include evaluation of EEG responses, 
responses in seizure diary, and assessment via Clinical Global 
Impression of Change (CGI-C). 
A 16-hour overnight video-EEG will be performed to look for 
changes from baseline, 
 
The investigator will also review seizure counts recorded by the 


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parent(s)/caregiver(s) in diaries to make certain seizure counts 
are not increasing. The seizure diaries will indicate whether 
spasms are still present. 
The CGI-C is a validated instrument that allows the investigator 
to rate the change in a patient’s condition on a 7-point scale 
ranging from “very much improved since the initiation of 
treatment” to “very much worse since the initiation of 
treatment”. 
Investigational Product, 
Dosage, and Route of 
Administration: 
Investigational product is a white to off-white powder. The 
dosage form received at each clinical study site is a glass bottle 
containing a nominal quantity of 100 mg of the powder 
JBPOS0101 active pharmaceutical ingredient (API) for 
reconstitution into an oral solution. 
Sample Size: 
Approximately, 50 patients will be screened of which around 
35 patients will be enrolled to provide at least 26 completers. At 
least 7 of the patients enrolled must be between 6 months 
through 12 months of age at the time of informed consent. 
Statistical Methods: 
The primary endpoint is the incidence of treatment-emergent 
adverse events (TEAEs). Safety results will be reported using 
summary tables, listings, and figures, as appropriate, for all 
patients in the safety population. 
The Medical Dictionary for Regulatory Activities (latest version) 
will be used to classify all AEs with respect to system organ 
class and preferred term. Adverse event summaries will include 
only TEAEs. 
Prior and concomitant medications will be summarized 
according to the World Health Organization Drug Dictionary. 
Numerical laboratory test results, vital sign measurements, and 
ECG data will be summarized for observed values and change 
from screening/baseline. Shifts from screening/baseline will also 
be presented for clinical laboratory findings according to normal 
range criteria, physical and neurological examination findings, 
and overall ECG interpretation findings. 


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Data listings will be provided for protocol-specified safety data.  
The secondary endpoints include plasma PK parameters AUC, 
Cmin, and Cmax. Other PK parameters may be calculated, as 
appropriate. Plasma PK parameters will be presented in a 
summary table, as data allow. Relationship between plasma 
investigational product levels and response will be studied.  
The efficacy analysis serves as the explorative endpoint. 
Version and Date of 
Protocol: 
Version 2.0 and 15 September 2020 


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List of Abbreviations 
Abbreviation 
Definition 
ACTH 
adrenocorticotrophic hormone 
AE 
adverse event 
AMPA 
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 
API 
active pharmaceutical ingredient 
AUC 
area under the concentration-time curve 
AUC0-24 
area under the concentration-time curve during 24 hours 
BASED 
Burden of Amplitudes and Epileptiform Discharges 
BID 
twice daily 
BMI 
body mass index 
BUN 
blood urea nitrogen 
CFR 
Code of Federal Regulations 
CGI-C 
Clinical Global Impression of Change 
CLtot/F 
apparent (oral) clearance 
CNS 
central nervous system 
Cmax 
maximum plasma concentration 
Cmin 
minimum plasma concentration 
DSMB 
Data Safety Monitoring Board 
EAS 
efficacy analysis set 
eCRF 
electronic case report form 
ECG 
electrocardiogram 
EEG 
electroencephalogram 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
hERG 
human rther-à-go-go-related gene 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IRB 
institutional review board 
IS 
infantile spasms 
LFT 
mEAS 
liver function tests 
Modified efficacy analysis set 
MedDRA 
Medical Dictionary for Regulatory Activities 


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Abbreviation 
Definition 
mGluR 
metabotropic glutamate receptor 
NMDA 
N-methyl-D-aspartate 
NOAEL 
no observed adverse effect level 
OTC 
over-the-counter 
PK 
pharmacokinetics 
PT 
preferred term 
Q1 
Quartile 1 
Q3 
Quartile 3 
QTcF 
QT interval from Fridericia’s formula 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SE 
status epilepticus 
SOC 
system organ class 
SOE 
schedule of events 
TEAE 
treatment-emergent adverse event 
tmax 
time to reach maximum plasma concentration 
ULN 
upper limit of normal 
WHODrug 
World Health Organization Drug Dictionary 
 
 


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1 
Introduction 
1.1 Overview of Infantile Spasms 
Infantile spasms (IS) is a rare form of epileptic encephalopathy that is specific to infancy and 
early childhood. This disease is associated with poor developmental outcome and results in 
significant disability (Eling et al 2002; Hrachovy and Frost 2013). The clinical 
manifestations of IS include brief tonic contractions of axial muscles which may be flexor, 
extensor, or mixed. They typically last 1-3 seconds each. The spasms may occur either in 
isolation or clusters but are more frequently observed in clusters and often occur on 
awakening (Hrachovy and Frost 2013). Infantile spasms carry very high mortality risks. A 
cohort study in the metropolitan area of Atlanta showed that by the age of 10 years there was 
a mortality ratio of 11.9 for IS – adjusted for the effects of age, race, and sex (Lux 2013). A 
long-term outcome study of patients with IS with history of infantile spasms reported 
mortality in 31% patients prior to early adulthood, of which 10% patients died prior to 
3 years, and 19% patients died prior to 10 years of age. Infection was the leading cause of 
death and most of the patients died due to underlying neurological disability (Riikonen 
1996). 
1.2 Approved Indications and Unmet Medical Need 
Infantile spasms is a devastating pediatric epilepsy syndrome with unsatisfactory treatment 
options. There are 2 treatments currently approved for IS: adrenocorticotrophic hormone 
(ACTH) and Sabril® (vigabatrin), however, none of them demonstrated a sustained cessation 
of IS (Nelson 2015). A large national infantile spasms consortium which followed infants 
with new-onset IS prospectively showed that only 46% of patients who received one of these 
first-line therapies responded (Knupp et al 2016a). Furthermore, of the children who failed 
on one first-line treatment and switched to receive the alternate first line treatment, only 55% 
responded (Knupp et al 2016b). Thus, that leaves nearly one third of infants who have 
spasms refractory to both first line agents. Importantly, the treatment with vigabatrin or 
high-dose steroids presents serious and potentially life-threatening adverse events (AEs) such 
as vision loss, sepsis or congestive heart failure (Tsao 2009; Chiron and Dulac 2015). 
Similarly, AEs associated with long-term use of ACTH limit their utility; physicians typically 
do not treat patients with ACTH for longer than 1 month. Most of the children develop 
Cushingoid features, obesity, and irritability. More serious AEs may include arterial 
hypertension, electrolyte imbalance, gastric ulcer, growth retardation, cardiomyopathy, and 


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immunosuppression (Shields 2006). Other treatments have been tested in uncontrolled 
studies but are not approved specifically for infantile spasms, including topiramate, 
zonisamide, valproic acid, nitrazepam, lamotrigine, levetiracetam, felbamate, high-dose 
pyridoxine, liposteroid, ganaxolone, intravenous immunoglobulin, ketogenic diet, and 
thyrotropin-releasing hormone. None of these therapies have demonstrated complete success 
in treating IS and are associated with adverse effects of varying severity (Nelson 2015). A 
large national spasms consortium which followed infants with new-onset IS prospectively, 
showed that only 9% of patients responded to nonstandard therapies (i.e., not ACTH and 
vigabatrin) (Knupp et al 2016a). 
1.3 Rationale for Using JBPOS0101 (Investigational Product) for 
Treatment of Infantile Spasms 
Infantile spasms is an epileptic encephalopathy that occurs in infancy with seizure-related 
developmental regression. There is increasing evidence that a longer duration of uncontrolled 
spasms is associated with poorer neurodevelopmental outcomes (Lux 2013). Therefore, 
therapies providing timely spasm suppression are critically needed. 
Glutamate is an excitatory neurotransmitter essential in both integrative brain functions and 
nervous system development (Swanson et al 2005). Glutamate receptors are categorized as 
ionotropic or metabotropic receptors. The ionotropic receptors comprise cation-specific ion 
channels and are subdivided into α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 
(AMPA) receptors and N-methyl-D-aspartate (NMDA) receptors. Very rapid neuronal 
excitation is a hallmark characteristic of glutamate transmission through the ionotropic 
receptors. The metabotropic glutamate receptors (mGluRs) having subtypes of 1-8, mediate 
relatively slow glutamate responses by coupling to intracellular signal transduction via 
G-proteins. The mGluR1 and mGluR5 belong to the Group 1 metabotropic receptor class and 
are localized to both pre- and post-synaptic terminals. These receptors modulate synaptic 
glutamate release, and antagonists of these receptors have neuroprotective effects (Bruno et 
al 2001). The Group 3 receptors, mGluR4 and mGluR7, are expressed primarily on 
presynaptic terminals, and their activation leads to decreases in glutamate release from 
presynaptic terminals. These modulators exhibit anticonvulsant activity and have a potential 
application in seizure disorders. The advantage of drugs that target the mGluRs is that they 
do not mediate, but rather modulate excitatory synaptic transmission, and are therefore, likely 
to be devoid of the undesirable effects resulting from the inhibition of excitatory synaptic 


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transmission, such as sedation or an impairment of learning and memory (Bruno et al 2001). 
JBPOS0101 has been shown to activate mGluR4 and inhibit mGluR1, mGluR5, and 
mGluR7, making it a promising drug for the treatment of IS. 
1.4 Summary of Nonclinical and Clinical studies 
1.4.1 
Nonclinical Summary 
The efficacy of the investigational product has been studied in numerous rodent models of 
seizure/epilepsy.
Expected, pharmacologically-based, clinical signs were observed with the investigational 
product in various safety pharmacology studies.
 
 


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1.4.2 
Clinical Summary 
The safety, tolerability, and pharmacokinetic (PK) profile of the investigational product was 
evaluated in a Phase 1, double-blind, randomized, placebo-controlled, single-center study 
carried out in young healthy male subjects aged 18 to 45 years old, with a body mass index 
(BMI) within the range of 19.0 kg/m2 to 30.0 kg/m2, inclusive, and a minimum weight of at 
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Details of clinical and nonclinical studies conducted with JBPOS0101 can be found in the 
Investigators’ Brochure. 
1.4.3 
Clinical versus Preclinical 
 


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2 
Study Objectives 
2.1 Primary Objective 
To evaluate the safety and tolerability of the investigational product in patients with 
refractory IS. 
2.2 Secondary Objective 
To characterize the PK of the investigational product in patients with refractory IS. 
2.3 Exploratory Objective 
To evaluate the efficacy of the investigational product in treating patients with refractory IS. 


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3 
Investigational Plan 
3.1 Study Design 
This is an open-label, multicenter study to evaluate the safety, tolerability, PK, and 
exploratory efficacy of the investigational product in children aged 6 months through 
36 months with IS. Patients will receive the investigational product at a dose of 6 mg/kg 
orally BID; once in the morning and 12 hours following the morning dose during the first 7 
days of Treatment Period 1. Starting from the PM dose on the day of Visit 3, the dose will be 
escalated and patients will receive the investigational product at a dose of 9 mg/kg orally 
twice daily. Starting on Day 15, the dose will be escalated again and patients will receive the 
investigational product at a dose of 15 mg/kg orally twice daily until the end of Treatment 
Period 1. 
The overall study duration is expected to be up to 84 days (± 5 days). As illustrated in 
Figure 3:1, the study is planned to include 4 periods: Screening Period (up to 28 days), 
Treatment Period 1 (28 days), Treatment Period 2 (Dose Tapering Period [14 days]), and a 
Follow-Up Period (14 days). There will be a total of 7 study visits and 6 telephone/email 
contacts. Overall, the study includes 3 overnight stays: one for screening procedures 
including video-electroencephalogram (EEG) recordings, one for Day 1 (Visit 2) PK 
sampling (Section 6.2) and AE monitoring, and one for Day 28 (Visit 5 [± 2 days]) 
video-electroencephalogram (EEG) recordings. 
During the Screening Period, Treatment Period 1, and Treatment Period 2, no changes to 
dosages of any drugs used for treating epileptic seizures are permitted (except for rescue 
medications used for acute treatment of breakthrough seizures which are not known to be 
CYP3A4 substrates and whose PK has not been shown to be impacted in the presence of a 
CYP3A4 inhibitor [see Appendix 13.3 for a non-exhaustive list of CYP3A4 substrates]). 
Changes of dosages of drugs used for treating epileptic seizures are permitted 2 or more days 
after the investigational product has been discontinued. 
Screening Period (Days -28 to -6):  
Eligible patients will complete all screening procedures and assessments within no more than 
28 days before the start of Treatment Period 1. Refer to Appendix 13.1 for the list of 
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shorter than 28 days as patients who meet study entry criteria will be eligible to receive the 
investigational product on the 6th day after completing all screening procedures and 
assessments. At the Screening Period visit (Visit 1), the investigator will ensure that the 
patient’s legal representative (parent[s]/caregiver[s]) provides a written informed consent 
form (ICF) on behalf of the infant patient. Patient’s parent(s)/caregiver(s) will receive a copy 
of the ICF for review and must provide the ICF prior to study participation. A 16-hour, 
video-EEG will be completed within the Screening Period (overnight video-EEG). Seizure 
diary will be distributed on the Screening Period visit (Visit 1) and families will be trained by 
the investigator or his/her delegate on how to log seizures. Patients will be allowed to be re-
screened once with the approval of the medical monitor or sponsor. 
Treatment Period 1 (Days 1 to 28):  
Patients will report to the hospital/clinic on Day 1 (Visit 2) and will remain at the clinical site 
for the first 24 hours following the first dose of investigational product. During Day 1 
(Visit 2), vital signs will be monitored. The first 2 doses of the investigational product 
(6 mg/kg orally) will be administered during Visit 2. Physical and neurological examinations 
will occur prior to the first dose on Day 1, and on Day 2 prior to discharge. The investigator 
or his/her delegate will contact the parent/caregiver by telephone or email during the next 
5 days (from Day 2 to 6) of Treatment Period 1 to ensure that the seizure diary is being 
completed, to review seizure counts, and to conduct daily assessments which includes 
following questions:  
• Have you noticed any change in seizure pattern? 
• Have you noticed an evolution of new seizure type? 
• Have you noticed any changes in appetite? 
• Have you noticed a change in stools? 
• Have you noticed excessive sedation? 
• Have you noticed excessive irritability? 
• Have you noticed the onset of new rash? 


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• Has your child experienced any possible AE? 
• Did your child take all prescribed doses of the investigational product today? 
• Did your child take all prescribed doses of other drugs used for treating epileptic 
seizures today? 
• Did your child require the use of a rescue medication for the treatment of a 
breakthrough seizure today? 
• What, if any, prescribed or over-the-counter medications is your child currently 
taking? 
The investigator will also contact the parent/caregiver by telephone on Day 12, or Day 13 or 
Day 14 to review seizure counts and to assess the patient’s status using the above questions. 
Patients will return to the study clinic on Day 7 (Visit 3 [± 2 days]). Starting from the PM 
dose on the day of Visit 3, the dose will be escalated and patients will receive the 
investigational product at a dose of 9 mg/kg orally twice daily. Starting on Day 15, the dose 
will be escalated again and patients will receive the investigational product at a dose of 15 
mg/kg orally twice daily until the end of Treatment Period 1. 
At Visit 2 and each visit thereafter, a record of the incidence and severity of TEAEs and 
SAEs will be collected and this will serve as a primary outcome criterion for this study. Other 
safety-related parameters such as 12-lead electrocardiogram (ECG), hematology, chemistry, 
physical examination, and vital signs will also be assessed at specified visits. Seizure diaries 
will be collected to assess spasms count prior to each visit following Visit 1. 
Video-EEG will be repeated at Day 28 (Visit 5 [± 2 days]) (overnight video-EEG), following 
Treatment Period 1 for the assessment of spasms and hypsarrhythmia. 
At Visit 2 and each visit thereafter, Clinical Global Impression of Change (CGI-C) will be 
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Treatment Period 2: Dose Tapering Period (Days 29 to 42): 
The full dose of the investigational product will be continued until Day 28. At the start of the 
Dose Tapering Period on Day 29, the dose will be reduced by half. On Day 35, the dose will 
be reduced by half again, and on Day 42, the investigational product will be stopped. Patients 
will return to the study clinic on Day 42 (Visit 6 [± 5 days]). Refer to Appendix 13.1 for list 
of tests/procedures. 
Follow-Up Period (Day 43 to 56): 
Patients will return to the study clinic on Day 56 (Visit 7 [± 5 days]). Refer to Appendix 13.1 
for list of tests/procedures. 


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Figure 3-1 
Study Design 
3.1.1 
Rationale of Study Design 
This open-label, multicenter study design allows the investigational product to be given as 
either add-on therapy or monotherapy. The design and choice of study population for this 
Phase 2 clinical study is based on the need to provide initial safety, tolerability, PK, and 
efficacy outcomes of the investigational product for future clinical studies. 
Screening Period 
Treatment Period 1 
Treatment Period 2: 
Dose Tapering Period 
Follow-up 
Visit 1 
Days -28 to -6 
Visit 2 to 5 
Days 1 to 28 
Visit 6 
Days 29 to 42 
Visit 7 
Days 43 to 56 
Administration of Open-label JBPOS0101 


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4 
Patient Selection and Withdrawal Criteria 
4.1 Selection of Study Population 
Approximately 50 patients will be screened of which, approximately 35 patients will be 
enrolled to target at least 26 patients as study completers at the appropriate number of study 
sites in the United States and Republic of Korea. At least 7 of the patients enrolled must be 
between 6 months through 12 months of age at the time of informed consent. Patients will be 
assigned to study treatment only if they meet all of the inclusion criteria and none of the 
exclusion criteria. 
Deviations from the inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability, or patient 
safety. Therefore, adherence to the criteria as specified in the protocol is essential. 
4.1.1 
Inclusion Criteria 
Each patient must meet all the following criteria to be enrolled in this study: 
1. Parent(s)/caregiver(s) fully comprehend and sign the ICF in accordance with 
applicable laws, regulations, and local requirements, understand all study procedures, 
and can communicate satisfactorily with the investigator and study coordinator. 
2. Is a male or female from 6 months through 36 months of age at the time of informed 
consent. 
3. Has clinical diagnosis of IS, confirmed by video-EEG analysis, and hypsarrhythmia 
on EEG at screening according to the Burden of Amplitudes and Epileptiform 
Discharges (BASED) scale score. 
4. As assessed by the investigator, has no or partial response to at least 2 out of the 
3 therapies of ACTH, vigabatrin, and glucocorticoids (i.e. prednisolone), or has no or 
partial response to at least 1 out of the 3 therapies of ACTH, vigabatrin, and 
glucocorticoids and is contraindicated to and/or refused by the patient’s legal 
representative(s) for treatment with 1 or both other 2 therapies. 


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5. Has general good health (defined as the absence of any clinically relevant 
abnormalities as determined by the investigator) based on physical and neurological 
examinations, medical history, normal renal function, and ECG, and clinical 
laboratory values completed during the Screening Period visit (Visit 1). 
6. Parent(s)/caregiver(s) is willing and able to comply with the study procedures and 
visit schedules in the opinion of the investigator. 
4.1.2 
Exclusion Criteria 
Patient meeting any of the following criteria will be excluded from the study: 
1. Is considered by the investigator, for any reason (including, but not limited to, the 
risks described as precautions and warnings in the current version of the 
investigator’s brochure for the investigational product) to be an unsuitable candidate 
to receive the investigational product. 
2. Has known or suspected allergy to the investigational product. 
3. Has known or suspected allergy to apple juice. 
4. Has clinically significant renal impairment, defined as creatinine >1.5 mg/dL or blood 
urea nitrogen (BUN) >2 × upper limit of normal (ULN). 
5. Has clinically significant liver dysfunction, defined as total bilirubin ≥2 × ULN, or 
aspartate aminotransferase or alanine aminotransferase ≥3 × ULN. 
6. Has clinically significant abnormal laboratory values; the investigator may deem the 
patient eligible if he/she judges the laboratory values to be not clinically significant. 
7. Has an ongoing or known history of human immunodeficiency virus infection, or 
chronic hepatitis B or C. 
8. Has a clinically significant abnormality on ECG that, in the opinion of the 
investigator, increases the safety risks of participating in the study. 
9. Has a neurodegenerative disorder as the underlying cause of IS. 
10. Has a known history of aspiration pneumonia within the past year. 
11. Has previously participated in another clinical study of the investigational product or 
received any investigational drug or device or investigational therapy within 30 days 
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12. Has received therapy with felbamate, cannabinoids, ketogenic diet or vagus nerve 
stimulation within 14 days of screening. 
13. Has received therapy with a medication known to be a CYP3A4 substrate and whose 
PK has been shown to be impacted in the presence of a CYP3A4 inhibitor within 14 
days of screening (see Appendix 13.3 for a non-exhaustive list of CYP3A4 
substrates). 
14. Has not remained at stables doses of all drugs used for treating epileptic seizures for 
at least 14 days prior to screening (except for rescue medications used for acute 
treatment of breakthrough seizures which are not known to be CYP3A4 substrates 
and whose PK has not been shown to be impacted in the presence of a CYP3A4 
inhibitor [see Appendix 13.3 for a non-exhaustive list of CYP3A4 substrates]). 
15. Has a lethal or potentially lethal condition other than infantile spasms, with a 
significant risk of death before 18 months of age such as non-ketotic 
hyperglycinemia. 
16. Has an underlying metabolic disease associated with glucose intolerance (e.g., 
glucose transporter deficiencies). 
17. Has a body weight below 5 kg. 
4.2 Withdrawal of Patients From the Study 
4.2.1 
Reasons for Withdrawal/Discontinuation 
Patients may withdraw from the study at any time and for any reason without prejudice to 
their future medical care by the investigator or at the study site. Every effort should be made 
to keep patients in the study. The reasons for patients not completing the study will be 
recorded. Reasons for patients being withdrawn from the study may include: 
• The patient does not meet the protocol inclusion or exclusion criteria. 
• The patient’s safety or welfare is at risk. 
• The patient is noncompliant with the protocol, defined as failure to perform any 
portion of scheduled assessments or procedures. 
• The patient has serious or intolerable AEs that, in the investigator’s opinion, require 
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• The patient is lost to follow-up. 
• The patient’s legal representative (parent(s)/caregiver(s)) withdraws consent or the 
investigator or sponsor decides to discontinue the patient’s participation in the study. 
The investigator will also withdraw a patient if Bio-Pharm Solutions Co., Ltd. terminates the 
study. Upon occurrence of a serious or intolerable AE, the investigator will confer with the 
sponsor. If a patient is discontinued because of an AE, the event will be followed until it is 
resolved. The patient’s legal representative (parent[s]/caregiver[s]) may withdraw his or her 
consent at any time. 
4.2.2 
Handling of Withdrawals 
Patients are free to withdraw from the study or study treatment at any time upon request. 
Patient participation in the study may be stopped at any time at the discretion of the 
investigator or at the request of the sponsor. 
At the discretion of the investigator, patients who withdraw from the study prematurely may 
receive tapered doses of investigational product before discontinuing. The tapering schedule 
for early withdrawal patients will be determined on a case-by-case basis and the medical 
monitor will be available for assistance if needed. When a patient withdraws from the study 
treatment or active participation in the study, the reason(s) for withdrawal shall be recorded 
by the investigator on the relevant page of the electronic case report form (eCRF). 
If a patient discontinues the study prematurely, investigator’s assessment of efficacy and 
tolerability of the investigational product will be recorded on Visit 6 (± 5 days). 
Whenever possible, all patients who discontinue study treatment or withdraw from the study 
prematurely will undergo all end-of-study (Visit 6) assessments. Patients who fail to undergo 
final assessments will be contacted by the study site in an attempt to have them comply with 
the protocol. Following a minimum of 2 documented unsuccessful telephone calls, a 
registered letter will be sent to the patient in a final attempt to ensure protocol compliance. 
It is vital to obtain follow-up data on any patient withdrawn because of an AE or SAE. In 
every case, efforts must be made to undertake protocol-specified safety follow-up 
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4.2.3 
Replacements 
A total of approximately 50 patients will be screened of which around 35 patients will be 
enrolled to provide at least 26 completers. At least 7 of the patients enrolled must be between 
6 months through 12 months of age at the time of informed consent. Patient screening and 
enrollment will be closed after 35 patients have begun Treatment Period 1. Patients who 
discontinue the study for any reason after dosing will not be replaced. 


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5 
Study Treatments 
5.1 Treatments Administered 
Investigational product will be administered at 6 mg/kg, orally twice daily, once in the 
morning and 12 hours following the morning dose during the first 7 days of Treatment Period 
1. Starting from the PM dose on the day of Visit 3, the dose will be escalated and patients 
will receive the investigational product at a dose of 9 mg/kg orally twice daily. Starting on 
Day 15, the dose will be escalated again and patients will receive the investigational product 
at a dose of 15 mg/kg orally twice daily until the end of Treatment Period 1. Each dose of the 
investigational product will be administered after at least a 2-hour fast. Food can be given 2 
hours after dosing. 
5.2 Identity of Investigational Product 
The investigational product is a white to off-white powder. The dosage form received at each 
clinical study site is a glass bottle containing a nominal quantity of 100 mg of the powder 
JBPOS0101 active pharmaceutical ingredient (API) for reconstitution into an oral solution. 
Each JBPOS0101 API powder-in-glass bottle received at the clinical study site is individually 
enclosed in a heat-sealed aluminum foil pouch. 
At the clinical study site, a pharmacist or authorized study personnel will dispense the 
JBPOS0101 API powder-in-glass bottle to the patient’s caregiver without the heat-sealed 
aluminum foil pouch enclosure. Before dispensing, the pharmacist or authorized study 
personnel will adjust the content of the JBPOS0101 API powder-in-glass bottle to reflect the 
proper dose to be administered to the patient; the proper dose will be based on bodyweight 
and will be determined by the investigator. For the subsequent administration of the clinical 
material that will be performed by the patient’s caregiver not at the clinical study site, the 
caregiver will be dispensed the customized doses of JBPOS0101 API powder-in-glass bottle 
in bulk packaging and will also be supplied with apple juice, an oral syringe and instructions 
for preparation of the solution for oral dosing. Other alternative dosing administration 
methods of the JBPOS0101 API powder-in-glass bottle may be permitted on a case-by-case 
basis with the approval of the sponsor and medical monitor. 
The JBPOS0101 API powder-in-glass bottle is to be mixed with room temperature apple 
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Patients will be dosed the full amount of solution using the oral syringe. Patients may also be 
dosed the solution via gastrostomy or nasogastric tube. Each individual dose should be 
prepared and used immediately. Any unused apple juice remaining in the individual packages 
of apple juice after making the oral solution is to be discarded. Any used or unused 
JBPOS0101 API powder-in-glass bottle is to be returned to the study site for reconciliation. 
5.3 Management of Clinical Supplies 
5.3.1 
Investigational Product Packaging and Storage 
Investigational product API powder-in-glass bottles will be prepared in boxes, stored and 
shipped by Bio-Pharm Solutions’ designee. There will be no randomization scheme and the 
medication will be dispensed at the study site by a pharmacist or authorized study personnel. 
The JBPOS0101 API powder-in-glass bottle, and JBPOS0101 API powder-in-glass bottle 
enclosed in the heat-sealed aluminum foil pouch, should be tightly capped and stored at room 
temperature (15°C – 30°C), protected from moisture and direct sunlight. The apple juice 
provided by the study sites should be stored at room temperature. Adequate care should be 
taken when handling the dosage form to avoid breakage of the glassware. 
The sponsor’s designee will ship adequate supplies of the investigational product to the study 
sites. 
5.3.2 
Investigational Product Accountability 
The investigator will maintain accurate records of receipt of all investigational product, 
including dates of receipt. In addition, the investigator must be able to account for all opened 
and unopened investigational product and accurate records will be kept regarding when and 
how many bottles of investigational product is dispensed and used by each patient, returned 
from each patient (if applicable), and disposed of at the site or returned to the sponsor or 
designee. Reasons for departure from the expected dispensing regimen must also be 
recorded. At the completion of the study, to satisfy regulatory requirements regarding drug 
accountability, all investigational product will be reconciled and retained or destroyed 
according to applicable regulations. All accountability records must be made available for 


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inspection by the sponsor and regulatory agency inspectors; copies must be provided to the 
sponsor at the conclusion of the study. 
5.4 Overdose Management 
An overdose is any dose of investigational product given to a patient that exceeds the dose 
described in the protocol. Any overdose, with or without associated AEs, must be promptly 
reported to the Sponsor Drug Safety Center. Overdoses without signs or symptoms do not 
need to be recorded as AEs; in case of any AEs associated with the overdose, these should be 
reported on relevant AE/SAE sections in the eCRF. 
5.4.1 
Treatment of Overdose 
There is no known antidote for JBPOS0101. In case of suspected overdose, patients should 
be treated per standard medical practice based on the investigator’s judgement. Dose delays 
and reductions may be implemented as necessary. Patients will be withdrawn from the study 
if persistent or unacceptable treatment-related toxicity is observed. 
5.5 Blinding 
This is an open-label study. 
5.6 Treatment Compliance 
Treatment compliance will be discussed with the patient’s legal representative 
(parent[s]/caregiver[s]) by the study site staff at each visit, and noncompliance will be noted 
based on details the study site obtains at the patient visits. Any missed dose against the 
instructions will be recorded in the eCRF. 
5.7 Prior and Concomitant Medication  
Use of all concomitant medications will be recorded in the patient’s eCRF. This will include 
all prescription drugs, herbal products, vitamins, minerals and over-the-counter (OTC) 
medications. The minimum requirement is that the medication name and the dates of 
administration are to be recorded. Any changes in concomitant medications will also be 
recorded in the patient’s eCRF. Use of drugs known to be CYP3A4 substrates and whose PK 
has been shown to be impacted in the presence of a CYP3A4 inhibitor (see Appendix 13.3 
for a non-exhaustive list of CYP3A4 substrates) will not be allowed during the Screening 


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Period, Treatment Period 1, and Treatment Period 2; use of drugs known to be CYP3A4 
substrates and whose PK has been shown to be impacted in the presence of a CYP3A4 
inhibitor will not be allowed until 2 or more days after the investigational product has been 
discontinued. Except for drugs known to be CYP3A4 substrates and whose PK has been 
shown to be impacted in the presence of a CYP3A4 inhibitor, concomitant medications for 
treating non-epileptic seizure disorders are acceptable but changes in dose(s) are discouraged. 
Concomitant drugs used for treating epileptic seizures will be allowed during the study 
(excluding felbamate, cannabinoids, and drugs used for treating epileptic seizures known to 
be CYP3A4 substrates and whose PK has been shown to be impacted in the presence of a 
CYP3A4 inhibitor) if the doses remain stable during the Screening Period, Treatment Period 
1, and Treatment Period 2 (with the exception that rescue medications used for acute 
treatment of breakthrough seizures which are not known to be CYP3A4 substrates and whose 
PK has not been shown to be impacted in the presence of a CYP3A4 inhibitor may be 
administered at any time during the study). Changes of dosages of drugs used for treating 
epileptic seizures are permitted 2 or more days after the investigational product has been 
discontinued. Ketogenic diet and vagus nerve stimulation therapies will not be allowed 
during the Screening Period, Treatment Period 1, and Treatment Period 2; ketogenic diet and 
vagus nerve stimulation therapies will not be allowed until 2 or more days after the 
investigational product has been discontinued. 
All medications taken by patients after the Screening Period visit until the completion of the 
final Follow-Up visit will be documented as concomitant medications (medication, dose, 
treatment duration, and indication). The reported medications will be reviewed and evaluated 
by the investigator to determine if they will affect a patient’s eligibility to participate or 
continue to participate in the study. 


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6 
Study Assessments and Procedures 
Before performing any study procedures, all legal representatives (parent[s]/caregiver[s]) of 
potential patients will sign an ICF. Patient’s legal representative (parent[s]/caregiver[s]) will 
have the opportunity to have any questions answered before signing the ICF. The investigator 
must address all questions raised by the patient’s legal representative (parent[s]/caregiver[s]). 
The investigator or designee will also sign the ICF. 
Study visits and timing of assessments and procedures are presented in the schedule of events 
(SOE; Appendix 13.1). 
6.1 Safety and Tolerability Assessments 
Safety variables will include physical and neurological examination findings, vital sign 
measurements (blood pressure, pulse, and respiratory rate), height, weight, BMI, ECG 
tracings, clinical laboratory test results (hematology, serum chemistry, and urinalysis), and 
reporting of AEs. 
Safety assessments will be conducted as shown in the SOE (Appendix 13.1). 
6.1.1 
Physical and Neurological Examination 
A complete physical examination will be performed at the time points indicated in the SOE 
(Appendix 13.1). A complete physical examination will include assessment of skin, head, 
ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular, abdomen, lymph nodes, 
and musculoskeletal system/extremities. 
A neurological examination will be performed at the time points indicated in the SOE 
(Appendix 13.1). Where possible, a neurological examination will include mental status 
evaluation, examination of cranial nerves, motor examination (muscle tone, strength, and 
reflexes), cerebellar examination (coordination and gait), and sensory examination. 
6.1.2 
Vital Sign Measurements, Height, Weight, and Body Mass Index 
Vital signs measurements will include blood pressure, temperature (measured rectally), pulse 
rate, and respiratory rate. Vital signs will be measured at the time points indicated in the SOE 
(Appendix 13.1). 


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Height, weight, and BMI will be measured at each clinic visit. 
The investigator will determine whether any of the vital sign measurements are clinically 
significant or not clinically significant. Clinical significance is defined as any variation in 
results that has medical relevance and may result in an alteration in medical care (e.g., active 
observation, diagnostic measures, or therapeutic measures). If a clinically significant change 
from the screening values is noted, the clinically significant value and reason for clinical 
significance will be documented on the AE page of the patient’s eCRF. The investigator will 
continue to monitor the patient with additional assessments until the value has reached the 
reference range, or the value at the Screening Period visit, or until the investigator determines 
that follow-up is no longer medically necessary. 
6.1.3 
Electrocardiograms 
Single 12-lead ECGs will be obtained at the time points indicated in the SOE 
(Appendix 13.1). Electrocardiogram assessments will be interpreted locally and will include 
comments on whether the tracings are normal or abnormal; rhythm, presence of arrhythmia 
or conduction defects; morphology, any evidence of myocardial infarction, or ST segment, T 
Wave, and U Wave abnormalities. In addition, measurements of the following intervals will 
be measured and reported: RR interval, PR interval, QRS width, QT interval, and QTcF. 
The investigator will determine whether any of the 12-lead ECG results are normal or 
abnormal, and if abnormal results are clinically significant or not clinically significant. 
Clinical significance is defined as any variation in results that has medical relevance and may 
result in an alteration in medical care (e.g., active observation, diagnostic measures, or 
therapeutic measures). If a clinically significant change from screening values is noted, the 
clinically significant value and reason for clinical significance will be documented on the AE 
page of the patient’s eCRF and a pediatric cardiology consultation will be prompted. The 
investigator will continue to monitor the patient with additional assessments until either the 
value has reached the reference range, or the value at the Screening Period visit, or until the 
investigator determines that follow-up is no longer medically necessary. 
6.1.4 
Clinical Laboratory Tests 
Blood and urine samples will be collected at the time points indicated in the SOE 
(Appendix 13.1). Hematology, coagulation and serum chemistry assessments will be 


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performed by the sponsor’s central laboratory; urinalysis assessment will be performed 
locally. 
The following hematology, coagulation, serum chemistry, and urinalysis assessments will be 
performed: 
Hematology: 
Hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration, mean corpuscular volume, platelet count, red 
blood cell count, and total and differential (absolute and percent) leukocyte 
count 
Coagulation 
International normalized ratio, partial thromboplastin time, and prothrombin 
time 
Serum 
Chemistry: 
Albumin, alanine aminotransferase, alkaline phosphatase, amylase, anion 
gap, aspartate aminotransferase, bicarbonate, bilirubin (total and direct), 
blood urea nitrogen, calcium, chloride, cholesterol (total, high-density 
lipoprotein, and low-density lipoprotein), creatine phosphokinase, 
creatinine, gamma-glutamyltransferase, globulin, glucose, lactate 
dehydrogenase, magnesium, phosphorus, potassium, sodium, total protein, 
triglycerides, and uric acid 
Urinalysis: 
Appearance, bilirubin, color, glucose, ketones, leukocyte esterase, 
microscopy (performed if dipstick is positive; includes bacteria, casts, 
crystals, epithelial cells, red blood cells, and white blood cells), nitrites, 
occult blood, pH, protein, specific gravity, turbidity, and urobilinogen 
Abnormal clinical laboratory values will be flagged as either high or low (or normal or 
abnormal) based on the reference ranges for each laboratory parameter. The investigator will 
determine whether any of the abnormally high or low results are clinically significant or not 
clinically significant. Clinical significance is defined as any variation in results that has 
medical relevance and may result in an alteration in medical care (e.g., active observation, 
diagnostic measures, or therapeutic measures). If a clinically significant change from the 
screening value is noted, the clinically significant value and reason for clinical significance 
will be documented on the AE page of the eCRF. The investigator will continue to monitor 
the patient with additional assessments until the value has reached the reference range, or the 


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value at the Screening Period visit, or until the investigator determines that follow-up is no 
longer medically necessary. 
Liver enzymes/LFTs will be assessed in accordance with the guidelines presented in the US 
Food and Drug Administration (FDA) Guidance for Industry–Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation (July 2009). 
6.1.5 
Adverse Events 
6.1.5.1 
Definitions of Adverse Events 
The investigator is responsible for reporting all TEAEs that are observed or reported during 
the study, regardless of their relationship to the investigational product or their clinical 
significance. 
An AE is defined as any untoward medical occurrence in a patient enrolled into this study 
regardless of its causal relationship to the investigational product. The patient’s legal 
representative (parent[s]/caregiver[s]) will be instructed to contact the investigator at any 
time if any symptoms develop. 
A TEAE is defined as any event not present before exposure to the investigational product or 
any event already present that worsens in either intensity or frequency after exposure to the 
investigational product. 
6.1.5.2 
Serious Adverse Events 
An SAE is defined as any event that results in death, is immediately life threatening, requires 
inpatient hospitalization or prolongation of existing hospitalization, results in persistent or 
significant disability/incapacity, or is a congenital anomaly/birth defect. Important medical 
events that may not result in death, be life threatening, or require hospitalization may be 
considered SAEs when, based upon appropriate medical judgment, they may jeopardize the 
patient or may require medical or surgical intervention to prevent one of the outcomes listed 
in this definition. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or doubling of 
seizure frequency compared to baseline over a period of 7 days or longer. 


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6.1.5.3 
Eliciting and Documenting Adverse Events 
Adverse events will be assessed from the time the patient’s legal representative 
(parent[s]/caregiver[s]) signs the ICF until and including the Follow-Up visit, 14 days after 
the last dose of the investigational product. 
Serious AEs that occur more than 14 days after the last dose of the investigational product 
need not be reported unless the investigator considers them related to the investigational 
product. 
At every study visit, the patient’s legal representative (parent[s]/caregiver[s]) will be asked a 
standard nonleading question to elicit any medically-related changes in the patient’s 
well-being. They will also be asked if the patient has been hospitalized, had any accidents, 
taken any new medications, or changed concomitant medication regimens (both prescription 
and OTC medications). 
In addition to patient observations, AEs identified from any study data (e.g., laboratory 
values, physical examination findings, and ECG changes) or identified from review of other 
documents (e.g., seizure diaries) that are relevant to patient safety will be documented on the 
AE page in the eCRF. 
6.1.5.4 
Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page in the eCRF. 
Information to be collected includes drug treatment, dose, event term, time of onset, 
investigator-specified assessment of severity and relationship to the investigational product, 
time of resolution of the event, seriousness, any required treatment or evaluations, and 
outcome. Adverse events resulting from concurrent illnesses, reactions to concurrent 
illnesses, reactions to concurrent medications, or progression of disease states must also be 
reported. All AEs will be followed to adequate resolution. The Medical Dictionary for 
Regulatory Activities (MedDRA) will be used to code all AEs. 
Any medical condition that is present at the time that the patient is screened but does not 
deteriorate should not be reported as an AE. However, if it deteriorates at any time during the 
study, it should be recorded as an AE. 


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6.1.5.5 
Reporting Serious Adverse Events 
Any AE that meets SAE criteria (Section 6.1.5.2) must be reported to Bio-Pharm Solutions 
Co., Ltd., immediately (i.e., within 24 hours) after the time that the study site personnel first 
learns about the event. The following contact information is to be used for SAE reporting: 
 
ICON Pharmacovigilance and Safety Services 
 
 
 
6.1.5.6 
Assessment of Severity 
The severity, or intensity, of an AE refers to the extent to which an AE affects the patient’s 
daily activities. The intensity of the AE will be rated as mild, moderate, or severe using the 
following criteria: 
Mild: 
These events require minimal or no treatment and do not interfere with the 
patient’s daily activities. 
Moderate: 
An AE that is sufficiently discomforting to interfere with normal activities. 
Severe: 
These events interrupt a patient’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually incapacitating. 
Changes in the severity of an AE should be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed. Adverse events characterized 
as intermittent do not require documentation of the onset and duration of each episode. 
6.1.5.7 
Assessment of Causality 
The investigator’s assessment of an AE’s relationship to the investigational product is part of 
the documentation process, but it is not a factor in determining what is or is not reported in 
the study. If there is any doubt as to whether a clinical observation is an AE, the event should 
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The relationship or association of the investigational product in causing or contributing to the 
AE will be characterized using the following classification and criteria: 
Unrelated: 
This relationship suggests that there is no association between the 
investigational product and the reported event. 
Possible: 
This relationship suggests that treatment with the investigational product 
caused or contributed to the AE, i.e., the event follows a reasonable temporal 
sequence from the time of drug administration or follows a known response 
pattern to the investigational product but could also have been produced by 
other factors. 
Probable: 
This relationship suggests that a reasonable temporal sequence of the event 
with drug administration exists and, based upon the known pharmacological 
action of the drug, known or previously reported adverse reactions to the drug 
or class of drugs, or judgment based on the investigator’s clinical experience, 
the association of the event with the investigational product seems likely. The 
event disappears or decreases on cessation or reduction of the dose of 
investigational product. 
Definite: 
This relationship suggests that a definite causal relationship exists between drug 
administration and the AE, and other conditions (concurrent illness, 
progression/expression of disease state, or concurrent medication reaction) do 
not appear to explain the event. The event reappears or worsens if the 
investigational product is re-administered. 
 
6.1.5.8 
Follow-up of Patients Reporting Adverse Events 
All AEs must be reported in detail on the appropriate page in the eCRF and followed to 
satisfactory resolution, until the investigator deems the event to be chronic or not clinically 
significant, or until the patient is considered to be stable. 
6.2 Pharmacokinetic Assessments 
6.2.1 
Pharmacokinetic Blood and Urine Samples 
Blood for the analysis of the investigational product in plasma will be collected on Day 1 
(Visit 2) and Day 21 (Visit 4 [± 2 days]) at the time points/intervals described in Table 13–2. 
Collections can be performed at any time during the collection intervals. The PK blood 
sampling scheme may be modified on a case-by-case so as not to exceed a total blood draw 
limit of 8 mL/kg over 56 days, to a maximum blood draw of 50 mL. Note that the total blood 
drawn accounts for both blood draws for PK assessment as well as other assessments (i.e., 


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clinical laboratory assessments). Urine sampling for PK assessment will be collected by 
using a plastic urine collection bag following the morning dosing of investigational product 
on Day 1 and Day 21 (Visit 4 [± 2 days]). Pharmacokinetic blood and urine samples may be 
used for future exploratory purposes outside of this study. 
6.2.2 
Pharmacokinetic Parameters 
Population PK analysis will be performed to calculate plasma PK parameters for the 
investigational product. The primary plasma PK parameters for the investigational product 
will include the AUC, minimum plasma concentration (Cmin), and Cmax. Other PK parameters 
may be calculated, as appropriate. Details regarding population PK analysis and PK 
parameters will be found in the statistical analysis plan (SAP) or Population PK modeling 
plan. 
6.3 Exploratory Efficacy Assessments 
Efficacy assessments will be performed as presented in the SOE (Appendix 13.1). 
6.3.1 
Electroencephalogram 
A 16-hour overnight video-EEG will be performed to look for changes from baseline, 
(Table 13–1). The 16-hour video-EEG will be conducted according to the current American 
Clinical Neurophysiology Society guidelines 1, 2, 4 and 5. The international 10/20 system 
(using all 21 electrodes) will be utilized for this study. Less than 21 electrodes may be used 
only in cases that there is clinical justification to do so (e.g. the presence of a scalp wound). 
6.3.2 
Seizure Diary 
The patient’s legal representative (parent[s]/caregiver[s]) will be provided with a seizure 
diary at the Screening Period visit (Visit 1) to record the number of seizures daily starting 
from the day after Visit 1 until the patient discontinues the investigational product. The 
seizure diaries will be assessed by the investigator as presented in the SOE (Appendix 13.1). 
The investigator will ensure that the seizure diary is being completed. The investigator will 
also review seizure counts to ensure the number of seizures is not increasing. The seizure 


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diaries will indicate whether spasms are still present.
 
 
6.3.3 
Clinical Global Impression of Change 
The CGI-C assessment will be performed by the investigator as presented in the SOE 
(Appendix 13.1). Additionally, the patient’s legal representative (parent[s]/caregiver[s]) will 
perform the CGI-C assessment at each visit. The CGI-C is a validated instrument that allows 
the investigator to rate the change in a patient’s condition on a 7-point scale ranging from 
“very much improved since the initiation of treatment” to “very much worse since the 
initiation of treatment.” The following 7-point scale (Spearing et al 1997) will be used to 
evaluate the patient’s condition after initiating the medication: 
Table 6–1 
Clinical Global Impression of Change Scale 
Scale # 
Impression 
1 
very much improved 
2 
much improved 
3 
minimally improved 
4 
no change 
5 
minimally worse 
6 
much worse 
7 
very much worse 
6.4 Safety Monitoring Committee 
An unblinded, independent Data Safety Monitoring Board (DSMB) will be established to 
provide an ongoing, independent review and assessment of safety data, to safeguard the 
interests and safety of the patients participating in the study. 
After 5 patients have completed Treatment Period 1, patient screening and enrollment will be 
halted and available safety data will be reviewed and assessed by the DSMB. Patient 
screening and enrollment can continue again following the DSMB's review and assessment 
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The frequency of DSMB data review meetings will be based on patient accruals. The first 
DSMB data review meeting will be held after 5 patients have completed Treatment Period 1. 
The second DSMB data review meeting will be held after 5 additional patients have 
completed Treatment Period 1 (after a total of 10 patients have completed Treatment Period 
1). The third DSMB data review meeting will be held after 10 additional patients have 
completed Treatment Period 1 (after a total of 20 patients have completed Treatment Period 
1), and the fourth DSMB data review meeting will be held after 10 additional patients have 
completed Treatment Period 1 (after a total of 30 patients have completed Treatment Period 
1). 
The committee may request additional meetings if it is deemed appropriate based on trends 
identified within the current data. The sponsor’s designee will be responsible for scheduling 
this type of meeting. 
The DSMB will adhere to a prospectively determined charter, which will be written by the 
sponsor and approved by the DSMB. The charter will define the responsibilities of the 
DSMB and sponsor, describe the conduct and frequency of the meetings and define the data 
sets to be reviewed. In addition, a special DSMB meeting will be convened if the 
safety-related study stopping rules are met and all serious TEAEs, TEAEs leading to 
investigational product discontinuation, and TEAEs leading to death will be reviewed. 
6.5 Sample Collections 
Blood and urine samples will be collected at the time points indicated in the SOE 
(Appendix 13.1). Blood and urine samples will be collected for PK assessment for the 
investigational product as described in Section 6.2.1. 
6.6 Unscheduled Visits 
All attempts should be made to keep the patients on the study schedule. Unscheduled visits 
may be necessary to repeat testing following abnormal laboratory results, for follow-up of 
AEs, or for any other reason, as warranted. 
 
 


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7 
Statistical and Analytical Plan 
A detailed SAP will be created and finalized prior to the database lock. The SAP will provide 
a detailed description of the statistical methods and expand on the summary provided in the 
protocol. This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoint definition and/or its analysis will also be reflected in a 
protocol amendment. Additional statistical analyses other than those described in this section 
may be performed as deemed appropriate and included in the SAP. 
7.1 Primary Safety Endpoints 
The safety endpoints are the incidence of TEAEs, vital sign measurements, physical and 
neurological examination findings, 12-Lead ECG findings, and clinical laboratory test 
results. 
7.2 Pharmacokinetic Endpoints 
• Primary PK endpoints include plasma PK parameters: AUC, Cmin, and Cmax for the 
investigational product. Other PK parameters may be calculated, as appropriate. 
• Relationship between plasma investigational product levels and response. 
7.3 Exploratory Efficacy Endpoints 
 
 


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7.4 Sample Size Calculations 
Approximately 50 patients will be screened of which around 35 patients will be enrolled to 
provide at least 26 completers. At least 7 of the patients enrolled must be between 6 months 
through 12 months of age at the time of informed consent. Patients who are screened and not 
dosed will be replaced. Patients who discontinue the study for any reason after dosing will 
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7.5 Analysis Sets 
The following analysis sets will be used in the statistical analyses. 
Safety analysis set: The safety analysis set will include all patients who were treated with at 
least one dose of the investigational product. The safety analysis set will be used for all safety 
assessments. 
Efficacy analysis set (EAS): The efficacy analysis set will include all patients, without any 
major protocol deviation affecting the efficacy endpoint analysis, who were treated with the 
investigational product for at least 26 days and completed the Day 28 (Visit 5 [± 2 days]) 
overnight video-EEG. The EAS will be used for all efficacy assessments.  
Pharmacokinetic (PK) analysis set: The PK analysis set will include all patients, without any 
major protocol deviation affecting the secondary endpoint analysis, who were treated with at 
least one dose of the investigational product and have at least one measurable PK 
concentration. The PK analysis set will be used for all PK assessments. 
Modified efficacy analysis set (mEAS): To evaluate the influence of COVID-19 on the 
efficacy results, a modified EAS will be considered which, in addition to the original EAS, 
includes also those patients with major protocol deviations affecting the efficacy endpoint 
analysis which can be attributed to COVID-19. The same efficacy analyses as in the EAS 
will also be performed for the mEAS. If both populations coincide (i.e., there are no major 
protocol violations attributable to COVID-19 which affect the efficacy endpoint analysis) 
only the analyses in the EAS will be performed. 
Other additional listings due to COVID-19 may be described in the SAP. 
The major protocol deviations leading to exclusion from the EAS and PK analysis set will be 
specified in the SAP and finalized prior to the database lock. 
7.6 Description of Subgroups to Be Analyzed 
Details will be provided in the SAP for any proposed subgroup analyses. 


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7.7 Statistical Analysis Methodology 
Summary statistics will be provided for all study endpoints. For continuous endpoints, the 
number of patients included, mean, standard deviation (SD), median, minimum, maximum, 
Quartile 1 (Q1), and Quartile 3 (Q3) will be provided. For categorical endpoints, the number 
and frequency in each category will be provided. Time to event endpoints will be 
summarized using median, 25%, and 75% percentiles. Statistical analysis system v9.3 (or 
higher) will be used throughout. 
Further details of the statistical analyses, methods, and data conventions are described in the 
SAP. 
No formal significance testing will be performed. 
7.7.1 
Analysis of Primary Safety Endpoint 
Investigational Product Administration and Exposure: Investigational product administration 
and exposure will be summarized and listed. Further details on the investigational product 
administration and exposure calculation will be given in the SAP. 
Medical History: Medical history details recorded at screening will be summarized and listed 
according to the coded MedDRA (latest version) by system organ class (SOC) and preferred 
term (PT). 
Prior and Concomitant Medications: Prior and concomitant medications will be summarized 
according to the World Health Organization Drug Dictionary (WHODrug). The number and 
percentage of patients will be presented for previous and concomitant medications. 
Adverse Events: AEs will be coded according to the coded MedDRA (latest version). 
Treatment-emergent AEs will be tabulated by SOC and PT. The following summary tables 
will be produced: 
• TEAEs 
• Treatment-related TEAEs 
• TEAEs leading to investigational product discontinuation 
• Treatment-related TEAEs leading to investigational product discontinuation 


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• Serious TEAEs 
• Treatment-related serious TEAEs 
• TEAEs leading to death 
• Treatment-related TEAEs leading to death. 
All AEs recorded during the study (including non-treatment-emergent AEs) will be listed. 
Physical and Neurological Examination: Descriptive summaries of change in examination 
findings from baseline to post-baseline visits will be presented by test in a shift table (normal, 
abnormal [not clinically significant], and abnormal [clinically significant]). 
Vital Signs: Descriptive by-visit summaries of vital signs data will be presented (including 
raw values and change from baseline). Vital signs will include blood pressures, temperature, 
pulse rate, and respiratory rate.  
Height, Weight, and BMI: Baseline height, weight, and BMI will be summarized and listed. 
ECGs: Descriptive summaries of change in overall assessment from baseline to post-baseline 
visits will be presented in a shift table (normal, abnormal [not clinically significant], and 
abnormal [clinically significant]). In addition, descriptive by-visit summaries of ECG data 
will be presented (including raw values and change from baseline). ECG data will include all 
of the following intervals: RR interval, PR interval, QRS width, QT interval, and QT interval 
from Fridericia’s formula (QTcF). 
Laboratory Safety Tests: Hematology, coagulation, serum chemistry, and urinalysis safety 
tests will be summarized by visit. Post-baseline visits will include change from baseline. 
7.7.2 
Pharmacokinetic Analyses 
Pharmacokinetic analyses will be based on the PK analysis set. 
Plasma PK concentrations for the investigational product will be presented in a data listing 
and summarized in tabular and graphical formats, as data allow. Overlay individual 
concentration-time plasma PK profiles may also be presented. Population PK analysis will be 
performed to calculate plasma PK parameters for the investigational product. Plasma PK 


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parameters for the investigational product will be listed and presented in a summary table, as 
data allow. 
7.7.3 
Analysis of Exploratory Efficacy Endpoints 
Descriptive analysis by-visit summaries of CGI-C assessment will be provided. Description 
of the CGI-C assessment is documented in the study reference manual. 
7.7.4 
Interim Analyses 
No interim analyses are planned. 


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8 
Data Quality Assurance 
Actions to ensure the accuracy and reliability of data will include the selection of qualified 
investigators and appropriate study centers; the review of protocol procedures with the 
investigator and associated study personnel prior to study start; the design of suitable source 
documents with appropriate instructions for use; the internal audit of source data according to 
Good Clinical Practice (GCP) and internal procedures to ensure their accuracy, completeness, 
and verifiability; as well as periodic study site monitoring by the sponsor. Written 
instructions will be provided for collection, preparation, and shipment of blood, plasma, and 
urine samples. 
The sponsor or its designee will review source documents for accuracy and completeness 
during on-site monitoring visits and after their return to the sponsor; any discrepancy will be 
resolved with the investigator or designee, as appropriate. The sponsor or its designee will 
perform the quality assurance and quality control activities of this study; however, 
responsibility for the accuracy, completeness, and reliability of the study data presented to 
the sponsor lies with the investigator generating the data. The data will be recorded into the 
clinical study database and verified for accuracy using the study-specific data verification 
plan. 
8.1 Data Management 
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate case histories for the patients treated as part of the research under this 
protocol. The investigator agrees to maintain accurate eCRFs and source documentation as 
part of the case histories. These source documents may include seizure diary, laboratory 
reports, ECG strips, etc. 
Study site personnel will enter patient data into an electronic data capture system. The 
analysis data sets will be a combination of these data and data from other sources (e.g., 
laboratory data). 
Clinical data management will be performed in accordance with applicable sponsor name 
standards and data cleaning procedures to ensure the integrity of the data (e.g., removing 
errors and inconsistencies in the data). Adverse event terms will be coded using MedDRA, an 


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internal validated medical dictionary, and concomitant medications will be coded using 
WHODrug. 
After database lock, each study site will receive a CD-ROM containing all of their 
site-specific eCRF data as entered into Oracle Clinical Remote Data Capture for the study, 
including full discrepancy and audit history. Additionally, a CD-ROM copy of all of the study 
site’s data from the study will be created and sent to the sponsor for storage. Sponsor will 
maintain a duplicate CD-ROM copy for their records. In all cases, patient initials will not be 
collected or transmitted to the sponsor. 


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9 
Ethics 
 
9.1 Institutional Review Board 
Federal regulations and the International Council for Harmonisation (ICH) guidelines require 
that approval be obtained from an institutional review board (IRB) before participation of 
human patients in research studies. Before study onset, the protocol, informed consent, 
advertisements to be used for the recruitment of study patients, and any other written 
information regarding this study to be provided to the patient’s legal representative must be 
approved by the IRB. Documentation of all IRB approvals and of the IRB compliance with 
ICH harmonised tripartite guideline E6(R2): GCP will be maintained by the study site and 
will be available for review by the sponsor or its designee. 
All IRB approvals should be signed by the IRB chairman or designee and must identify the 
IRB name and address, the clinical protocol by title or protocol number or both, and the date 
approval or a favorable opinion was granted. 
The investigator is responsible for providing written summaries of the progress and status of 
the study at intervals not exceeding 1 year or otherwise specified by the IRB. The 
investigator must promptly supply the sponsor or its designee, the IRB, and, where 
applicable, the institution, with written reports on any changes significantly affecting the 
conduct of the study or increasing the risk to patients. 
9.2 Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki, ICH, GCP, the protocol, and all applicable regulations. 
9.3 Patient Information and Consent 
A written informed consent in compliance with US Title 21 Code of Federal Regulations 
(CFR) Part 50 shall be obtained from each patient’s legal representative 
(parent[s]/caregiver[s]) before entering the study or performing any unusual or nonroutine 
procedure that involves risk to the patient. An ICF template may be provided by the sponsor 
to study sites. If any institution-specific modifications to study-related procedures are 
proposed or made by the study site, the consent should be reviewed by the sponsor or its 
designee or both before IRB submission. Once reviewed, the consent will be submitted by 


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the investigator to his or her IRB for review and approval before the start of the study. If the 
ICF is revised during the study, all patient’s legal representatives (parent[s]/caregiver[s]) 
must sign the revised form. 
Before recruitment and enrollment, each prospective patient’s legal representative 
(parent[s]/caregiver[s]) will be given a full explanation of the study and be allowed to read 
the approved ICF. Once the investigator is assured that the patient’s legal representative 
(parent[s]/caregiver[s]) understands the implications of participating in the study, the 
patient’s legal representative (parent[s]/caregiver[s]) will be asked to give consent on behalf 
of the patient to participate in the study by signing the ICF. 
The investigator shall retain the signed original ICF(s) and give a copy of the signed original 
form to the patient’s legal representative (parent[s]/caregiver[s]). 


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10 Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of the 
study but may be subject to change based on industry and government standard operating 
procedures, working practice documents, or guidelines. Changes will be reported to the IRB 
but will not result in protocol amendments. 
10.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain patient confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of patient’s legal representative (parent[s]/caregiver[s]), except as necessary for 
monitoring and auditing by the sponsor, its designee, the US FDA, or the IRB. 
The investigator and all employees and coworkers involved with this study may not disclose 
or use for any purpose other than performance of the study any data, record, or other 
unpublished confidential information disclosed to those individuals for the purpose of the 
study. Prior written agreement from the sponsor or its designee must be obtained for the 
disclosure of any said confidential information to other parties. 
10.2 Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow the sponsor to 
submit the complete and accurate certification or disclosure statements required under 
21 CFR 54. In addition, the investigator must provide to the sponsor a commitment to 
promptly update this information if any relevant changes occur during the course of the 
investigation and for 1 year following the completion of the study. 
The sponsor is not financially responsible for further testing or treatment of any medical 
condition that may be detected during the screening process. In addition, in the absence of 
specific arrangements, the sponsor is not financially responsible for further treatment of the 
patient’s disease. 


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10.3 Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 8.2 
and Title 21 of the CFR by providing essential documents, including but not limited to the 
following: 
• IRB approval. 
• Original investigator-signed investigator agreement page of the protocol. 
• Form FDA 1572, fully executed, and all updates on a new fully executed Form 
FDA 1572. 
• Curriculum vitae for the investigator and each subinvestigator listed on Form 
FDA 1572. 
• Financial disclosure information to allow the sponsor to submit complete and accurate 
certification or disclosure statements required under 21 CFR 54. In addition, the 
investigators must provide to the sponsor a commitment to promptly update this 
information if any relevant changes occur during the course of the investigation and 
for 1 year after the completion of the study. 
• IRB-approved ICF, samples of study site advertisements for recruitment for this study, 
and any other written information regarding this study that is to be provided to the 
legal representative (parent[s]/caregiver[s]). 
• Laboratory certifications and normal ranges for any local laboratories used by the 
study site, in accordance with 42 CFR 493. 
10.4 Study Conduct 
The investigator agrees that the study will be conducted according to the principles of ICH 
E6(R2). The investigator will conduct all aspects of this study in accordance with all 
national, state, and local laws or regulations. Study information from this protocol will be 
posted on publicly available clinical trial registers before enrollment of patients begins. 
10.5 Adherence to Protocol 
The investigator agrees to conduct the study as outlined in this protocol in accordance with 
ICH E6(R2) and all applicable guidelines and regulations. 


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10.6 Adverse Events and Study Report Requirements 
By participating in this study, the investigator agrees to submit reports of SAEs to the 
sponsor and/or IRB according to the timeline and method outlined in the protocol. In 
addition, the investigator agrees to submit annual reports to the study site IRB as appropriate. 
10.7 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the 
institution; the investigator/institution should provide the IRB with a summary of the study’s 
outcome and the sponsor and regulatory authority(ies) with any reports required. 
10.8 Records Retention 
Essential documents should 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 at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirements or by an agreement with the sponsor. It is the responsibility of the sponsor to 
inform the investigator/institution as to when these documents no longer need to be retained. 
10.9 Publications 
After completion of the study, the data may be considered for reporting at a scientific 
meeting or for publication in a scientific journal. In these cases, the sponsor will be 
responsible for these activities and will work with the investigators to determine how the 
manuscript is written and edited, the number and order of authors, the publication to which it 
will be submitted, and other related issues. The sponsor has final approval authority over all 
such issues. 
Data are the property of the sponsor and cannot be published without prior authorization 
from the sponsor. 


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11 Study Management 
11.1 Monitoring 
11.1.1 
External Data Monitoring Committee 
An unblinded, independent DSMB will periodically review safety data. The frequency of 
data review and DSMB processes are outlined in the DSMB charter. The charter will define 
the responsibilities of the DSMB and sponsor, describe the conduct and frequency of the 
meetings, and define the data sets to be reviewed. 
11.1.2 
Monitoring of the Study 
The clinical monitor, as a representative of the sponsor, has the obligation to follow the study 
closely. In doing so, the monitor will visit the investigator and study site at periodic intervals, 
in addition to maintaining necessary telephone and letter contact. The monitor will maintain 
current personal knowledge of the study through observation, review of study records and 
source documentation, and discussion of the conduct of the study with the investigator and 
personnel. 
All aspects of the study will be carefully monitored, by the sponsor or its designee, for 
compliance with applicable government regulation with respect to current GCP and current 
standard operating procedures. 
11.1.3 
Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, 
audits, IRB review, and regulatory inspections by providing direct access to all study records. 
In the event of an audit, the investigator agrees to allow the sponsor, representatives of the 
sponsor, or a regulatory agency (e.g., FDA) access to all study records. 
The investigator should promptly notify the sponsor of any audits scheduled by any 
regulatory authorities and promptly forward copies of any audit reports received to the 
sponsor. 


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11.2 Management of Protocol Amendments and Deviations 
11.2.1 
Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an apparent 
immediate hazard to the patient, must be reviewed and approved by the sponsor or its 
designee. Amendments to the protocol must be submitted in writing to the Investigator’s IRB 
for approval before patients can be enrolled into an amended protocol. 
11.2.2 
Protocol Deviations 
The investigator or designee must document and explain in the patient’s source 
documentation any deviation from the approved protocol. The investigator may implement a 
deviation from, or a change of, the protocol to eliminate an immediate hazard to study 
patients without prior IRB approval. As soon as possible after such an occurrence, the 
implemented deviation or change, the reasons for it, and any proposed protocol amendments 
should be submitted to the IRB for review and approval, to the sponsor for agreement, and to 
the regulatory authorities, if required. 
A deviation from the protocol is an unintended or unanticipated departure from the 
procedures or processes approved by the sponsor and the IRB and agreed to by the 
investigator. A significant deviation occurs when there is nonadherence to the protocol by the 
patient or investigator that results in a significant additional risk to the patient. Significant 
deviations can include nonadherence to inclusion or exclusion criteria or nonadherence to 
FDA regulations or ICH GCP guidelines and will lead to the patient being withdrawn from 
the study (Section 4.2). 
Protocol deviations will be documented by the clinical monitor throughout the course of 
monitoring visits. Principal investigators will be notified in writing by the monitor of 
deviations. The IRB should be notified of all protocol deviations in a timely manner. 
11.3 Study Termination 
Although Bio-Pharm Solutions Co., Ltd. has every intention of completing the study, 
Bio-Pharm Solutions Co., Ltd. reserves the right to discontinue the study at any time for 
clinical or administrative reasons. 


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The end of the study is defined as the date on which the last patient completes the last visit 
(includes the Follow-Up Visit). 
11.4 Final Report 
Whether the study is completed or prematurely terminated, the sponsor will ensure that the 
clinical study reports are prepared and provided to the regulatory agency as required by the 
applicable regulatory requirements. The sponsor will also ensure that the clinical study 
reports in marketing applications meet the standards of the ICH harmonised tripartite 
guideline E3: Structure and content of clinical study reports. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results. 
Upon completion of the clinical study report, the sponsor will provide the investigator with 
the full summary of the study results. The investigator is encouraged to share the summary 
results with the patient’s legal representative, as appropriate. The study results will be posted 
on publicly available clinical trial registers. 


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12 Reference List 
Bruno V, Battaglia G, Copani A, et al. Metabotropic glutamate receptor subtypes as targets 
for neuroprotective drugs. J Cereb Blood Flow Metab. 2001;21(9):1013-33. 
Chiron C, Dulac O. Analysis of vigabatrin treatment causing visual field defects in infantile 
spasms. Dev Med Child Neurol. 2015;57(1):9-10. 
Eling P, Renier WO, Pomper J, et al. The mystery of the doctor’s son, or the riddle of West 
syndrome. Neurology. 2002;58(6):953-5. 
Hrachovy RA, Frost JD Jr. Infantile spasms. Handb Clin Neurol. 2013;111:611-8. 
Knupp KG, Coryell J, Nickels KC, et al. Response to treatment in a prospective national 
infantile spasms cohort. Ann Neurol. 2016a;79(3):475-84. 
Knupp KG, Leister E, Coryell J, et al; Pediatric Epilepsy Research Consortium. Response to 
second treatment after initial failed treatment in a multicenter prospective infantile spasms 
cohort. Epilepsia. 2016b;57(11):1834-42. 
Lux AL. Latest American and European updates on infantile spasms. Curr Neurol Neurosci 
Rep. 2013;13(3):334. 
Nelson GR. Management of infantile spasms. Transl Pediatr. 2015;4(4):260-70. 
Riikonen R. Long-term outcome of West syndrome: a study of adults with a history of 
infantile spasms. Epilepsia. 1996;37(4):367-72. 
Shields WD. Infantile spasms: little seizures, BIG consequences. Epilepsy Curr. 
2006;6(3):63-9. 
Spearing MK, Post RM, Leverich GS, et al. Modification of the Clinical Global Impressions 
(CGI) Scale for use in bipolar illness (BP): the CGI-BP. Psychiatry Res. 1997;73(3):159–71. 
Swanson CJ, Bures M, Johnson MP, et al. Metabotropic glutamate receptors as novel targets 
for anxiety and stress disorders. Nat Rev Drug Discov. 2005;4(2):131-44. 
Tsao CY. Current trends in the treatment of infantile spasms. Neuropsychiatr Dis Treat. 
2009;5:289-99.


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13 Appendices 
13.1 Appendix: Schedule of Events 
Table 13–1 
Schedule of Events 
Procedure 
Screening 
Period 
 
Treatment Period 1 
Treatment Period 
2: Dose Tapering 
Period 
Follow-
Up 
Visit 
Visit 1 
Visit 2 
Telephone 
Contact 
Visit 3 
Telephone 
Contact 
Visit 4 
Visit 5 
Visit 6 / Early 
Termination Visit 
Visit 7 
Study Days 
–28 to -6 
1 
2 to 6a 
7 
 
12 or 13 
or 14a 
21 
28 
 
42 
56 
Visit Window 
 
 
 
± 2 days 
 
± 2 days 
± 2 days 
± 5 days 
± 5 days 
Informed consent 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
Video EEGb 
X 
 
 
 
 
 
X 
 
 
BASED Score 
X 
 
 
 
 
 
X 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
12-lead electrocardiogram 
X 
 
 
X 
 
 
X 
X 
 
Urine drug screenc 
X 
 
 
 
 
 
 
 
 
Physical and neurological 
examinationd 
X 
X 
Xe 
X 
 
X 
X 
X 
X 
Vital sign measurementsf 
X 
X 
 
X 
 
X 
X 
X 
X 
Clinical laboratory testsg 
X 
 
 
X 
 
 
X 
X 
 
Investigational product 
administrationh 
 
X 
X 
X 
X 
X 
X 
 
 


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Procedure 
Screening 
Period 
 
Treatment Period 1 
Treatment Period 
2: Dose Tapering 
Period 
Follow-
Up 
Visit 
Visit 1 
Visit 2 
Telephone 
Contact 
Visit 3 
Telephone 
Contact 
Visit 4 
Visit 5 
Visit 6 / Early 
Termination Visit 
Visit 7 
Study Days 
–28 to -6 
1 
2 to 6a 
7 
 
12 or 13 
or 14a 
21 
28 
 
42 
56 
Visit Window 
 
 
 
± 2 days 
 
± 2 days 
± 2 days 
± 5 days 
± 5 days 
Dispensing of investigational 
product 
 
X 
 
X 
 
X 
X 
 
 
Investigational product 
accountability assessment 
 
 
 
X 
 
X 
X 
X 
X 
Adverse event monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
Review of prior and 
concomitant medicationsi 
X 
X 
X 
X 
 
X 
X 
X 
X 
Clinical Global Impression of 
Changem 
 
X 
 
X 
 
X 
X 
X 
 
Seizure diaryj 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pharmacokinetic blood 
samplingk 
 
X 
 
 
 
X 
 
 
 
Pharmacokinetic urine 
samplingl 
 
X 
 
 
 
X 
 
 
 
Abbreviations: EEG, electroencephalogram 
a. The investigator or his/her delegate will follow-up by telephone or email on Day 2 to Day 6 to ensure that the seizure diary is being completed, to 
review seizure counts, and to conduct daily assessments. The investigator will also contact the parent/caregiver by telephone on Day 12, or Day 13 
or Day 14 to review seizure counts and to assess the patient’s status.  
b. An overnight video-EEG will be completed within the Screening Period (Days -28 to -6), and repeated at Day 28 (Visit 5 [± 2 days]),
c. Urine drug screen assessment to test for the presence of cannabinoids will be performed locally. 
d. A complete physical examination will include assessment of skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular, 


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abdomen, lymph nodes, and musculoskeletal system/extremities. Where possible, a neurological examination will include mental status evaluation, 
examination of cranial nerves, motor examination (muscle tone, strength, and reflexes), cerebellar examination (coordination and gait), and sensory 
examination. Physical and neurological examination will also be conducted on Day 2 prior to discharge. 
e. After physical and neurological examination is conducted on Day 2, physical and neurological examination is not scheduled to be conducted again 
until Day 7 (Visit 3 [± 2 days]). 
f. Vital signs measurements will include blood pressures, temperature (measured rectally), pulse rate, and respiratory rate. Height, weight, and body 
mass index (BMI) will be measured at each clinic visit. Vital sign measurements will also be conducted on Day 2, prior to discharge. 
g. Includes urinalysis. Hematology, coagulation and serum chemistry assessments will be performed by the sponsor’s central laboratory; urinalysis 
assessment will be performed locally. 
h. Investigational product will be administered orally twice daily, in the morning and 12 hours after the morning dose at a dose of 6 mg/kg after at 
least a 2-hour fast during the first 7 days of Treatment Period 1. Starting from the PM dose on the day of Visit 3, the dose will be escalated and 
patients will receive the investigational product at a dose of 9 mg/kg orally twice daily. Starting on Day 15, the dose will be escalated again and 
patients will receive the investigational product at a dose of 15 mg/kg orally twice daily until the end of Treatment Period 1. The first 2 doses of the 
investigational product (6 mg/kg orally) will be administered during Visit 2 and the remaining doses will be administered at home. Patients will 
receive investigational product up to Day 28 (Treatment Period 1). Following Treatment Period 1, Treatment Period 2 (Dose Tapering Period) will 
begin on Day 29 and the dose will be reduced by half for all patients. On Day 35, the dose will be reduced by half again, and on Day 42, the 
investigational product will be stopped. 
i. Prior medications will be recorded during the Screening Period. All medications taken by patients after Screening Period until the completion of 
the final Follow-Up visit will be documented as concomitant medications. 
j. Seizure diary will be distributed on the Screening Period visit (Visit 1). The investigator will ensure that the seizure diary is being completed. The 
investigator will also review seizure counts to make sure seizures are not increasing. The seizure diaries will indicate whether spasms are still 
present. 
 
 
 
 
 
 
. 
 
k. Details regarding PK blood sampling are provided in Table 13–2. 
l. Urine sampling for PK assessment will be collected by using a plastic urine collection bag following the morning dosing of investigational product 
on Day 1 and Day 21 (Visit 4 [± 2 days]). 
m. The Clinical Global Impression of Change is completed by both the Investigator and the Caregiver. CGI-C on Day 1 is performed prior to dosing. 
 


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13.2 Appendix: Pharmacokinetic Sampling 
Table 13–2 
Steady State Pharmacokinetic Sampling Time Points 
Study Period 
Blood Sampling Time Pointsa 
Visit 
Study Days 
2b 
1 
• 
0.5-1.5 hours post-AM dose 
• 
4-6 hours post-AM dose  
• 
8 hours post-AM dose time point and pre-PM dose 
4b 
21 
• 
0.5-1.5 hours post-AM dose 
• 
4-6 hours post-AM dose 
• 
8 hours post-AM dose time point and pre-PM dose 
a. The PK blood sampling scheme may be modified on a case-by-case basis so as not to exceed a total blood draw limit of 
8 mL/kg over 56 days, to a maximum blood draw of 50 mL. Note that the total blood drawn accounts for both blood 
draws for PK assessment as well as other assessments (i.e., clinical laboratory assessments). 
b. The AM dose should be administered at the clinical site prior to the PK blood sampling on Visit 2 & 4. 


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13.3 Appendix: List of Excluded Medications 
• alfentanil 
• alprazolam 
• amlodipine 
• aprepitant 
• aripiprazole 
• astemizole 
• atorvastatin 
• avanafil 
• boceprevir 
• budesonide 
• buspirone 
• carbamazepine 
• cafergot 
• cerivastatin 
• chlorpheniramine 
• cilostazol 
• cisapride 
• clarithromycin 
• codeine-N-demethylation 
• colchicine 
• conivaptan 
• cyclosporine 
• dapsone 


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• darifenacin 
• darunavir 
• dasatinib 
• dexamethasone 
• dextromethorphan 
• diazepam 
• diltiazem 
• docetaxel 
• domperidone 
• dronedarone 
• ebastine 
• eletriptan 
• eliglustat 
• eplerenone 
• erythromycin 
• estradiol 
• everolimus 
• felodipine 
• fentanyl 
• finasteride 
• gleevec 
• haloperidol 
• hydrocortisone 
• ibrutinib 
• indinavir 


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• irinotecan 
• lercanidipine 
• levo-α-acetylmethadol 
• lidocaine 
• lomitapide 
• lovastatin 
• lurasidone 
• maraviroc 
• methadone 
• midazolam 
• naloxegol 
• nateglinide 
• nelfinavir 
• nevirapine 
• nifedipine 
• nisoldipine 
• nitrendipine 
• ondansetron 
• pimozide 
• prednisolone 
• prednisone 
• progesterone 
• propranolol 
• quetiapine 
• quinidine 


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• quinine 
• rilpivirine 
• risperidone 
• ritonavir 
• rivaroxaban 
• romidepsin 
• salmeterol 
• saquinavir 
• sildenafil 
• simvastatin 
• sirolimus 
• sorafenib 
• sunitinib 
• tacrolimus 
• tadalafil 
• tamoxifen 
• taxol 
• telaprevir 
• telithromycin 
• terfenadine 
• testosterone 
• ticagrelor 
• tipranavir 
• tolvaptan 
• torisel 


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• trazodone 
• triazolam 
• vardenafil 
• vemurafenib 
• verapamil 
• vincristine 
• zaleplon 
• ziprasidone 
• zolpidem 


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13.4 Appendix: Summary of Changes to Protocol CL-0101-WS01 
 
 
 
 
SUMMARY OF CHANGES OF  
PROTOCOL CL-0101-WS01 2.0 
PRODUCT: JBPOS0101 
 
Revision: 
2.0 
Date of Revision: 
September 15, 2020 
This Version 
Replaces Revision: 
 
1.3 (April 9, 2020) 
 
 
CONFIDENTIALITY STATEMENT 
The confidential information in this document is provided to you as an investigator or consultant for review 
by you, your staff, and the applicable Institutional Review Board/Independent Ethics Committee. Your 
acceptance of this document constitutes agreement that you will not disclose the information contained 
herein to others without written authorization from Bio-Pharm Solutions Co. Ltd. 
 
 
 


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13.4.1 
Regulatory History and Overview  
This revision is effective on 15 September 2020, and will be submitted to all applicable 
Institutional Review Boards (IRBs), Independent Ethics Committees (IECs), or Research 
Ethics Boards (REBs), and Regulatory Authorities. 
Table 13-3: 
Summary of Protocol CL-0101-WS01 Revision History 
Version and Date 
Reason for Revision 
Revision 1.0 
March 1, 2019 
Initial protocol to support Phase 2 study entitled: A Phase 2 Study to 
Assess the Safety, Tolerability, Exploratory Efficacy, and 
Pharmacokinetics of Orally Administered JBPOS0101 for Refractory 
Infantile Spasms Patients (Protocol Number CL-0101-WS01). 
Revision 1.1  
May 15, 2019 
 
Revision 1.2 
September 19, 2019 
Revision 1.3 
April 9, 2020 
 
Revision 2.0 
September 15, 2020 
 
 
 
 


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13.4.2 
Summary of Changes 
The following changes have been made to the protocol entitled A Phase 2 Study to Assess the 
Safety, Tolerability, Exploratory Efficacy, and Pharmacokinetics of Orally Administered 
JBPOS0101 for Refractory Infantile Spasms Patients (Protocol Number CL-0101-WS01), 
Revision 1.3, dated 9 April 2020: 
Protocol Section 
Description of Change 
General 
• Version and date updated throughout the document from Version 1.3, 
9 April 2020 to Version 2.0, 15 September 2020 
Protocol Synopsis  
List of Abbreviations 
• 
3.1 Study Design 
 
4.1.1 Inclusion Criteria 
4.1.2 Exclusion Criteria 
 


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Protocol Section 
Description of Change 
5.3.1 Investigational Product 
Packaging and Storage 
6.2.1 Pharmacokinetic 
Blood and Urine Samples 
6.4 Safety Monitoring 
Committee 
 
7.4 Sample Size 
Calculations 
7.5 Analysis Sets 
13.1 Appendix: Schedule of 
Events 
. 
 

SAP_001.pdf: 
 
Bio-Pharm Solutions Co., Ltd. 
Protocol No. CL-0101-WS01 
ICON Project No. 4508-0001 
Statistical Analysis Plan  
05 Mar 2021 
 
 
 
CONFIDENTIAL 
Page 1 of 45 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
 
A Phase 2 Study to Assess the Safety, Tolerability, Exploratory Efficacy, and 
Pharmacokinetics of Orally Administered JBPOS0101 for Refractory 
Infantile Spasms Patients 
 
 
Final Version 2.0 
Date: 05 March 2021 
 
for 
 
Protocol No. CL-0101-WS01 
 
 
Submitted to: 
Bio-Pharm Solutions Co., Ltd. 
6F, C Bldg., Advanced Institute of Convergence Technology 
145 Gwanggyo-Ro, Yeongtong-Gu Suwon, Gyeonggi-Do 
Korea 16229 
 
 
Prepared by: 
ICON Clinical Research, LLC 
820 West Diamond Avenue, Suite 100 
Gaithersburg, MD 20878 
 
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Protocol No. CL-0101-WS01 
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Statistical Analysis Plan  
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SIGNATURES PAGE 
 
ICON Development Solutions, LLC (ICON) Signature Page 
ICON Authors: 
 
 
ICON Reviewers: 
 
 
 
 
 
 
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Statistical Analysis Plan  
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ICON Approvals: 
 
 
 
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Statistical Analysis Plan  
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CONFIDENTIAL 
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SPONSOR SIGNATURE PAGE 
 
Sponsor Approval: 
 
 
Director, Department of Clinical 
Executive Director 
 
 
 
 
 
 
 
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Protocol No. CL-0101-WS01 
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Statistical Analysis Plan 
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CONFIDENTIAL 
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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
AEDs 
anti-epileptic drugs 
ATC 
anatomical therapeutic chemical  
AUC 
area under the plasma concentration-time curve  
BASED 
burden of amplitudes and epileptiform discharges 
BID 
twice daily 
BLQ 
Below limit of quantification 
BMI 
body mass index 
CI 
confidence interval 
CGI-C 
clinical global impression of change 
Cmax 
maximum plasma concentration 
Cmin 
minimum plasma concentration 
CSR 
clinical study report 
CV 
coefficient of variation 
DMP 
data management plan 
EAS 
efficacy analysis set 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EEG 
electroencephalogram 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
GM 
geometric mean 
HR 
heart rate 
ICF 
informed consent form 
ICH 
International Council for Harmonization 
IS 
infantile spasms 
LFT 
liver function tests 
mEAS      
Modified efficacy analysis set 
MedDRA 
Medical Dictionary for Regulatory Activities 
NONMEM 
Non-linear Mixed Effects Modeling 
OTC 
over-the-counter 
PK 
pharmacokinetic(s) 
PT 
preferred term 
Q1 
quartile 1 
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Protocol No. CL-0101-WS01 
ICON Project No. 4508-0001 
Statistical Analysis Plan 
05 Mar 2021
 
 
CONFIDENTIAL 
Page 6 of 45 
 
Abbreviation 
Definition 
Q3 
quartile 3 
QTcF 
QT interval from Fridericia’s formula 
SAE 
serious adverse event 
SAP 
statistical Analysis Plan 
SD 
standard deviation 
SOC 
system organ class 
SQRT 
square root 
TEAE 
treatment-emergent adverse event 
 
 
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Bio-Pharm Solutions Co., Ltd. 
Protocol No. CL-0101-WS01 
ICON Project No. 4508-0001 
Statistical Analysis Plan 
05 Mar 2021
 
 
CONFIDENTIAL 
Page 7 of 45 
 
TABLE OF CONTENTS 
SIGNATURES PAGE ...................................................................................................................2 
SPONSOR SIGNATURE PAGE ..................................................................................................4 
LIST OF ABBREVIATIONS .......................................................................................................5 
TABLE OF CONTENTS ..............................................................................................................7 
1 
INTRODUCTION .........................................................................................................9 
2 
STUDY OBJECTIVES AND ENDPOINTS .............................................................10 
2.1 
Primary Objectives ..............................................................................................10 
2.2 
Secondary Objective ............................................................................................10 
2.3 
Exploratory Objective .........................................................................................10 
2.4 
Study Endpoints ...................................................................................................10 
2.4.1 
Primary Safety Endpoints ......................................................................................10 
2.4.2 
PK Endpoints .........................................................................................................10 
2.4.3 
Exploratory Efficacy Endpoints .............................................................................10 
3 
STUDY DESIGN .........................................................................................................12 
3.1 
General ..................................................................................................................12 
3.2 
Study Population ..................................................................................................17 
3.3 
Evaluations at Screening and Check-in .............................................................17 
3.4 
Randomization and Treatment Assignments ....................................................17 
3.5 
Study Drug Administration ................................................................................17 
3.6 
Compliance ...........................................................................................................17 
3.7 
Pharmacokinetic Sampling Schedule .................................................................17 
3.8 
Evaluation of Treatment Safety ..........................................................................18 
3.8.1 
Adverse Events ......................................................................................................18 
3.8.2 
Clinical Laboratory Assessments ...........................................................................19 
3.8.3 
Vital Signs, Height, Weight, and Body Mass Index ..............................................20 
3.8.4 
Electrocardiograms ................................................................................................20 
3.8.5 
Physical and Neurological Examinations ..............................................................21 
3.8.6 
Concomitant Medications ......................................................................................21 
3.8.7 
Protocol Deviation Reporting ................................................................................22 
4 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED 
ANALYSIS ..................................................................................................................24 
5 
QUALITY CONTROL AND QUALITY ASSURANCE METHODS FOR 
DATA ANALYSIS ......................................................................................................25 
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6 
PHARMACOKINETIC AND EFFICACY ASSESSMENTS ................................26 
6.1 
Pharmacokinetic Assessments ............................................................................26 
6.1.1 
Pharmacokinetic Analysis ......................................................................................26 
6.2 
Efficacy Assessments ...........................................................................................26 
6.2.1 
Electroencephalogram............................................................................................26 
6.2.2 
Seizure Diary .........................................................................................................27 
6.2.3 
Clinical Global Impression of Change ...................................................................27 
7 
STATISTICAL METHODS ......................................................................................29 
7.1 
General ..................................................................................................................29 
7.2 
Handling of Dropouts or Missing Data ..............................................................29 
7.2.1 
Handling of incomplete dates for AE ....................................................................29 
7.2.2 
Handling missing or partial Prior/Concomitant Medication Dates ........................30 
7.3 
Examination of Subgroups ..................................................................................31 
7.4 
Analysis Populations ............................................................................................31 
7.5 
Subject Accountability.........................................................................................32 
7.6 
Protocol Deviation Reporting .............................................................................32 
7.7 
Subject Demographics and Baseline Characteristics .......................................32 
7.8 
Medical and Surgical History .............................................................................32 
7.9 
Extent of Exposure ...............................................................................................33 
7.10 
Analysis of Exploratory Efficacy Data ...............................................................33 
7.10.1 
EEG ........................................................................................................................33 
7.10.2 
Seizure Diary .........................................................................................................35 
7.10.3 
CGI-C .....................................................................................................................35 
7.11 
Analysis of Pharmacokinetic Data .....................................................................35 
7.12 
Analysis of Safety Data ........................................................................................36 
7.12.1 
Adverse Events ......................................................................................................36 
7.12.2 
Clinical Laboratory Assessments ...........................................................................37 
7.12.3 
Vital Signs, Height, Weight, and Body Mass Index ..............................................37 
7.12.4 
Electrocardiograms ................................................................................................37 
7.12.5 
Physical and Neurological Examinations ..............................................................38 
7.12.6 
Prior and Concomitant Medications ......................................................................38 
7.12.7 
COVID-19..............................................................................................................38 
7.13 
Sample Size ...........................................................................................................39 
7.14 
Interim Analysis ...................................................................................................39 
7.15 
General Conventions for Tables, Listings and Figures ....................................40 
8 
TABLES, FIGURES, AND LISTINGS .....................................................................41 
 
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1 
INTRODUCTION 
This statistical analysis plan (SAP) is consistent with the statistical methods section of the final 
study protocol (Version 2.0, dated 15 September 2020) and includes additional detail of safety, 
tolerability, exploratory efficacy and pharmacokinetic (PK) summaries to be included in the 
clinical study report (CSR). 
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2 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
Primary Objectives 
• To evaluate the safety and tolerability of the investigational product in patients with 
refractory Infantile Spasms (IS). 
2.2 
Secondary Objective 
• To characterize the PK of the investigational product in patients with refractory IS. 
2.3 
Exploratory Objective 
• To evaluate the efficacy of the investigational product in treating patients with refractory 
IS. 
2.4 
Study Endpoints 
2.4.1 
Primary Safety Endpoints 
• Incidence of Treatment emergent Adverse Events (TEAEs) 
• Vital signs 
• Electrocardiograms (ECGs) 
• Physical and Neurological examinations 
• Clinical laboratory assessments 
2.4.2 
PK Endpoints 
• Primary PK endpoints include plasma PK parameters: area under the concentration-
time curve (AUC), minimum plasma concentration (Cmin) and maximum plasma 
concentration (Cmax) 
• Relationship between plasma investigational product levels and response  
2.4.3 
Exploratory Efficacy Endpoints 
• 
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3 
STUDY DESIGN 
3.1 
General 
This is an open-label, multicenter study to evaluate the safety, tolerability, PK, and exploratory 
efficacy of the investigational product in children aged 6 months through 36 months with IS. 
Patients will receive the investigational product at a dose of 6 mg/kg orally twice daily (BID); 
once in the morning and 12 hours following the morning dose during the first 7 days of 
Treatment Period 1. Starting from the PM dose on the day of Visit 3, the dose will be escalated 
and patients will receive the investigational product at a dose of 9 mg/kg orally twice daily. 
Starting on Day 15, the dose will be escalated again and patients will receive the investigational 
product at a dose of 15 mg/kg orally twice daily until the end of Treatment Period 1.
 Table 3-1 Schedule of Event. 
The overall study duration is expected to be up to 84 days (± 5 days). As illustrated in Figure 3-1, 
the study is planned to include 4 periods: Screening Period (up to 28 days), Treatment Period 1 
(28 days), Treatment Period 2 (Dose Tapering Period [14 days]), and a Follow-Up Period (14 
days). There will be a total of 7 study visits and 6 telephone/email contacts. Overall, the study 
includes 3 overnight stays: one for screening procedures, one for Day 1 (Visit 2) PK sampling 
and AE monitoring, and one for Day 28 (Visit 5 [± 2 days]) video-EEG recordings. 
During the Screening Period, Treatment Period 1, and Treatment Period 2, no changes to dosages 
of any drugs used for treating epileptic seizures are permitted (except for rescue medications 
used for acute treatment of breakthrough seizures which are not known to be CYP3A4 substrates 
and whose PK has not been shown to be impacted in the presence of a CYP3A4 inhibitor). 
Changes of dosages of drugs used for treating epileptic seizures are permitted 2 or more days 
after the investigational product has been discontinued.  
The study design of the study is depicted in Figure 3-1. 
Figure 3-1 
  
 
 
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Figure 3-1 
  
Screening Period 
Treatment Period 1 
Treatment Period 2:
Dose Tapering Period
Follow-up 
Visit 1
Days -28 to -6
Visit 2 to 5
Days 1 to 28
Visit 6
Days 29 to 42
Visit 7
Days 43 to 56
Administration of Open-label JBPOS0101 
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Error! Reference source not found. Table 3-1 Schedule of Events 
 
 
Procedure
 
Screening 
Period
 
Treatment Period 1
Treatment Period 2: 
Dose Tapering Period
 
Follow- 
Up 
Visit 
Visit 1 
Visit 2 
Telephone 
Contact 
Visit 3 
Telephone 
Contact 
Visit 4 
Visit 5 
Visit 6 / Early 
Termination Visit 
Visit 7 
Study Days 
–28 to -6
1 
2 to 6a 
7 
12 or 13 or
14a 
21 
28 
42 
56 
Visit Window 
 
 
 
± 2 days  
± 2 days 
± 2 days 
± 5 days 
± 5 days 
Informed consent 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
Video EEGb 
X 
 
 
 
 
 
X 
 
 
BASED Score 
X 
 
 
 
 
 
X 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
12-lead electrocardiogram 
X 
 
 
X 
 
 
X 
X 
 
Urine drug screenc 
X 
 
 
 
 
 
 
 
 
Physical and neurological
X 
X 
Xe 
X 
X 
X 
X 
X 
examinationd 
Vital sign measurementsf 
X 
X 
 
X 
 
X 
X 
X 
X 
Clinical laboratory testsg 
X 
 
 
X 
 
 
X 
X 
 
Investigational product
X 
X 
X 
X 
X 
X 
administrationh 
 
 
 
 
 
 
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Procedure 
Screening  
Treatment Period 1 
Treatment Period 2: 
Dose Tapering 
Period 
 
Follow- 
Period 
Up 
Visit 
Visit 1 
Visit 2 
Telephone
Visit 3 
Telephone 
Visit 4 
 
Visit 5 
Visit 6 / Early 
Termination Visit 
 
Visit 7 
Contact
Contact
 
Study Days 
 
–28 to -6  
1 
 
 
2 to 6a 
 
7 
12 or 13 or  
21 
 
 
28 
42 
 
 
56 
14a 
Visit Window 
 
 
 
± 2 days  
± 2 days 
± 2 days 
± 5 days 
± 5 days 
Dispensing of investigational 
X 
 
X 
X 
X 
 
 
product
 
 
 
Investigational product 
 
X 
X 
X 
X 
X 
accountability assessment 
 
Adverse event monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
Review of prior and
X 
X 
X 
X 
X 
X 
X 
X 
concomitant medicationsi 
Clinical Global Impression of 
X 
 
X 
X 
X 
X 
 
Changem 
 
 
Seizure diaryj 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pharmacokinetic blood 
X 
 
X 
 
 
 
samplingk 
 
 
 
 
Pharmacokinetic urine
X 
 
X 
 
 
 
samplingl 
 
 
 
 
Abbreviations: EEG, electroencephalogram 
a.  The investigator or his/her delegate will follow-up by telephone or email on Day 2 to Day 6 to ensure that the seizure diary is being completed, to 
review seizure counts, and to conduct daily assessments. The investigator will also contact the parent/caregiver by telephone on Day 12, or Day 13 or 
Day 14 to review seizure counts and to assess the patient’s status. 
b.  An overnight video-EEG will be completed within the Screening Period (Days -21 to -6), and repeated at Day 28 (Visit 5 [± 2 days]),
c.  Urine drug screen assessment to test for the presence of cannabinoids will be performed locally. 
d.  A complete physical examination will include assessment of skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular, 
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abdomen, lymph nodes, and musculoskeletal system/extremities. Where possible, a neurological examination will include mental status evaluation, 
examination of cranial nerves, motor examination (muscle tone, strength, and reflexes), cerebellar examination (coordination and gait), and sensory 
examination. Physical and neurological examination will also be conducted on Day 2 prior to discharge. 
e.  After physical and neurological examination is conducted on Day 2, physical and neurological examination is not scheduled to be conducted again until 
Day 7 (Visit 3 [± 2 days]). 
f.   Vital signs measurements will include blood pressures, temperature (measured rectally), pulse rate, and respiratory rate. Height, weight, and body mass 
index (BMI) will be measured at each clinic visit. Vital sign measurements will also be conducted on Day 2, prior to discharge. 
g.  Includes urinalysis. Hematology, coagulation and serum chemistry assessments will be performed by the sponsor’s central laboratory; urinalysis 
assessment will be performed locally. 
h.  Investigational product will be administered orally twice daily, in the morning and 12 hours after the morning dose at a dose of 6 mg/kg after at least a 2-
hour fast during the first 7 days of Treatment Period 1. Starting from the PM dose on the day of Visit 3, the dose will be escalated and patients will receive 
the investigational product at a dose of 9 mg/kg orally twice daily. Starting on Day 15, the dose will be escalated again and patients will receive the 
investigational product at a dose of 15 mg/kg orally twice daily until the end of Treatment Period 1. The first 2 doses of the investigational product (6 
mg/kg orally) will be administered during Visit 2 and the remaining doses will be administered at home. Patients will receive investigational product up to 
Day 28 (Treatment Period 1). Following Treatment Period 1, Treatment Period 2 (Dose Tapering Period) will begin on Day 29 and the dose will be reduced 
by half for all patients. On Day 35, the dose will be reduced by half again, and on Day 42, the investigational product will be stopped. 
i.   Prior medications will be recorded during the Screening Period. All medications taken by patients after Screening Period until the completion of the 
final Follow-Up visit will be documented as concomitant medications. 
j.   Seizure diary will be distributed on the Screening Period visit (Visit 1). The investigator will ensure that the seizure diary is being completed. The 
investigator will also review seizure counts to make sure seizures are not increasing. 
 
 
k.  Details regarding PK blood sampling are provided in Table 3–2. 
l.   Urine sampling for PK assessment will be collected by using a plastic urine collection bag following the morning dosing of investigational product on Day 
1 and Day 21 (Visit 4 [± 2 days]). 
m. The Clinical Global Impression of Change is completed by both the Investigator and the Caregiver. CGI-C on Day 1 is performed prior to dosing. 
 
Source: Protocol Final Version 2.0, dated 15 September 2020.
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3.2 
Study Population 
This study will enroll male and female subjects meeting the following criteria: they are between 
6 months through 36 months of age at the time of informed consent, have a clinical diagnosis of 
IS, confirmed by video-EEG analysis, and hypsarrhythmia on EEG at screening according to the 
BASED scale score. 
3.3 
Evaluations at Screening and Check-in 
The screening period will be a maximum of 28 days and will include Day -28 to Day -6 prior to 
first dose of study drug. Refer toError! Reference source not found. Table 3-1 Schedule of 
EventError! Reference source not found. Table 3-1 Schedule of Event for screening and check-in 
procedures. 
3.4 
Randomization and Treatment Assignments 
This is an open-label study.  
3.5 
Study Drug Administration 
Investigational product will be administered at 6 mg/kg, orally twice daily, once in the morning 
and 12 hours following the morning dose during the first 7 days of Treatment Period 1. Starting 
from the PM dose on the day of Visit 3, the dose will be escalated and patients will receive the 
investigational product at a dose of 9 mg/kg orally twice daily. Starting on Day 15, the dose will 
be escalated again and patients will receive the investigational product at a dose of 15 mg/kg 
orally twice daily until the end of Treatment Period 1. Each dose of the investigational product 
will be administered after at least a 2-hour fast. Food can be given 2 hours after dosing.  
3.6 
Compliance 
Treatment compliance will be discussed with the patient’s legal representative 
(parent[s]/caregiver[s]) by the study site staff at each visit, and noncompliance will be noted 
based on details the study site obtains at the patient visits. Any missed dose against the 
instructions will be recorded in the electronic case report form (eCRF). 
3.7 
Pharmacokinetic Sampling Schedule 
PK blood sampling will be performed at time points mentioned in Table 3-2 Steady State 
Pharmacokinetic Sampling Time Points. 
 
 
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Table 3-2 Steady State Pharmacokinetic Sampling Time Points 
Study Period 
Visit                       Study Days 
 
Blood Sampling Time Pointsa 
•   0.5-1.5 hours post-AM dose 
•   4-6 hours post-AM dose 
•   8 hours post-AM dose time point and pre-PM dose 
2b 
1 
4b 
21 
•
•
•
0.5-1.5 hours post-AM dose 
4-6 hours post-AM dose 
8 hours post-AM dose time point and pre-PM dose 
a.   The PK blood sampling scheme may be modified on a case-by-case basis so as not to exceed a total blood draw limit of 
8 mL/kg over 56 days, to a maximum blood draw of 50 mL. Note that the total blood drawn accounts for both 
blood draws for PK assessment as well as other assessments (i.e., clinical laboratory assessments). 
b.   The AM dose should be administered at the clinical site prior to the PK blood sampling on Visit 2 & 4. 
Urine sampling for PK assessment will be collected for the morning dosing of investigational 
product on Day 1 and Day 21 (Visit 4 [± 2 days]). 
Pharmacokinetic blood and urine samples may be used for future exploratory purposes outside of 
this study. 
3.8 
Evaluation of Treatment Safety 
3.8.1 
Adverse Events 
An AE is defined as any untoward medical occurrence in a patient enrolled into this study 
regardless of its causal relationship to the investigational product. The patient’s legal 
representative (parent[s]/caregiver[s]) will be instructed to contact the investigator at any time if 
any symptoms develop. 
A TEAE is defined as any event not present before exposure to the investigational product or any 
event already present that worsens in either intensity or frequency after exposure to the 
investigational product. 
All AEs will be reported or observed during the study will be recorded on the AE form in the 
eCRF.  The AE and SAE reporting period begins after administration of study drug through the 
follow up visit. The Investigator will follow-up on all AEs observed or reported by the subject up 
to the end of the reporting period unless the event stabilizes and follow-up is no longer 
necessary.  The Investigator will follow-up on SAEs until they are considered resolved or the 
outcome is known. 
The following details will be collected for AEs: description of the AE, onset date/time,  action 
taken with study drug (dose not changed, drug interrupted, drug withdrawn, dose increased, not 
applicable, or unknown), date/time of resolution, any additional treatment given, outcome 
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(recovered/resolved, not recovered/not resolved, recovered/resolved with sequelae, 
recovering/resolving, fatal or unknown), severity (mild, moderate, severe), seriousness (yes, no), 
relationship to study drug (unrelated, possibly, probably, definitely related or unknown), and 
whether the AE causes early termination of the subject.  
The severity of AEs will be categorized as follows: 
• Mild: These events require minimal or no treatment and do not interfere with the patient’s 
daily activities. 
• Moderate: An AE that is sufficiently discomforting to interfere with normal activities. 
• Severe: These events interrupt a patient’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually incapacitating. 
 
3.8.2 
Clinical Laboratory Assessments 
Blood and urine samples will be collected for hematology, coagulation, serum chemistry and 
urinalysis at the time points on Screening and Day 7, Day 28 and on Day 42. 
Hematology: 
Hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration, mean corpuscular volume, platelet count, red 
blood cell count, and total and differential (absolute and percent) leukocyte 
count 
Coagulation 
International normalized ratio, partial thromboplastin time, and prothrombin 
time 
Serum 
Chemistry: 
Albumin, alanine aminotransferase, alkaline phosphatase, amylase, anion 
gap, aspartate aminotransferase, bicarbonate, bilirubin (total and direct), 
blood urea nitrogen, calcium, chloride, cholesterol (total, high-density 
lipoprotein, and low-density lipoprotein), creatine phosphokinase, 
creatinine, gamma-glutamyltransferase, globulin, glucose, lactate 
dehydrogenase, magnesium, phosphorus, potassium, sodium, total protein, 
triglycerides, and uric acid 
Urinalysis: 
Appearance, bilirubin, color, glucose, ketones, leukocyte esterase, 
microscopy (performed if dipstick is positive; includes bacteria, casts, 
crystals, epithelial cells, red blood cells, and white blood cells), nitrites, 
occult blood, pH, protein, specific gravity, turbidity, and urobilinogen 
 
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Abnormal clinical laboratory values will be flagged as either high or low (or normal or 
abnormal) based on the reference ranges for each laboratory parameter. The investigator will 
determine whether any of the abnormally high or low results are clinically significant or not 
clinically significant. Clinical significance is defined as any variation in results that has medical 
relevance and may result in an alteration in medical care (e.g., active observation, diagnostic 
measures, or therapeutic measures). If a clinically significant change from the screening value is 
noted, the clinically significant value and reason for clinical significance will be documented on 
the AE page of the eCRF. The investigator will continue to monitor the patient with additional 
assessments until the value has reached the reference range, or the value at the Screening Period 
visit, or until the investigator determines that follow-up is no longer medically necessary. 
Liver enzymes/LFTs will be assessed in accordance with the guidelines presented in the US Food 
and Drug Administration (FDA) Guidance for Industry–Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation (July 2009). 
Urine drug screen assessment will be performed locally at screening time point. 
3.8.3 
Vital Signs, Height, Weight, and Body Mass Index 
Vital signs measurements will include blood pressure, temperature (measured rectally), pulse 
rate, and respiratory rate. Vital signs will be measured at Screening, Treatment Period 1 on Day 
1, Day 2 prior to discharge, Day 7, Day 21 and Day 28, Treatment Period 2 on Day 42 and 
Follow-Up visit on Day 56. Height, weight, and body mass index (BMI) will be measured at 
each clinic visit.. 
3.8.4 
Electrocardiograms 
The 12-lead ECG will be measured at following time points: Screening, Treatment Period 1 on 
Day 7 and 28, and Treatment Period 2 on Day 42. 
ECG parameters will include RR interval, PR interval, QRS width, QT interval, and QT interval 
from Fridericia’s formula (QTcF). Subjects with ECG assessments will be interpreted locally and 
will include comments on whether the tracings are normal or abnormal; rhythm, presence of 
arrhythmia or conduction defects; morphology, any evidence of myocardial infarction, or ST 
segment, T Wave, and U Wave abnormalities.  
The investigator will determine whether any of the 12-lead ECG results are normal or abnormal, 
and if abnormal results are clinically significant or not clinically significant. Clinical significance 
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is defined as any variation in results that has medical relevance and may result in an alteration in 
medical care (e.g., active observation, diagnostic measures, or therapeutic measures). If a 
clinically significant change from screening values is noted, the clinically significant value and 
reason for clinical significance will be documented on the AE page of the patient’s eCRF and a 
pediatric cardiology consultation will be prompted.  
3.8.5 
Physical and Neurological Examinations 
Subjects with complete physical and neurological examination will be documented at Screening, 
Day 1, Day 2 prior to discharge, Day 7, Day 21 and Day 28 of Treatment Period 1, Day 42 of 
Treatment Period 2 and Follow-Up visit on Day 56. 
A complete physical examination will include assessment of skin, head, ears, eyes, nose, throat, 
neck, thyroid, lungs, heart, cardiovascular, abdomen, lymph nodes, and musculoskeletal 
system/extremities. 
A neurological examination will include mental status evaluation, examination of cranial nerves, 
motor examination (muscle tone, strength, and reflexes), cerebellar examination (coordination 
and gait), and sensory examination. 
3.8.6 
Concomitant Medications 
Use of all concomitant medications will be recorded in the patient’s eCRF. This will include all 
prescription drugs, herbal products, vitamins, minerals and over-the-counter (OTC) medications. 
The minimum requirement is that the medication name and the dates of administration are to be 
recorded. Any changes in concomitant medications will also be recorded in the patient’s eCRF. 
Use of drugs known to be CYP3A4 substrates and whose PK has been shown to be impacted in 
the presence of a CYP3A4 inhibitor will not be allowed during the Screening Period, Treatment 
Period 1, and Treatment Period 2; use of drugs known to be CYP3A4 substrates and whose PK 
has been shown to be impacted in the presence of a CYP3A4 inhibitor will not be allowed until 2 
or more days after the investigational product has been discontinued. 
Concomitant drugs used for treating epileptic seizures will be allowed during the study 
(excluding felbamate, cannabinoids, and drugs used for treating epileptic seizures known to be 
CYP3A4 substrates and whose PK has been shown to be impacted in the presence of a CYP3A4 
inhibitor) if the doses remain stable during the Screening Period, Treatment Period 1, and 
Treatment Period 2 (with the exception that rescue medications used for acute treatment of 
breakthrough seizures which are not known to be CYP3A4 substrates and whose PK has not 
been shown to be impacted in the presence of a CYP3A4 inhibitor may be administered at any 
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time during the study). Changes of dosages of drugs used for treating epileptic seizures are 
permitted 2 or more days after the investigational product has been discontinued. Ketogenic diet 
and vagus nerve stimulation therapies will not be allowed during the Screening Period, 
Treatment Period 1, and Treatment Period 2; ketogenic diet and vagus nerve stimulation 
therapies will not be allowed until 2 or more days after the investigational product has been 
discontinued.  
Prior/concomitant medications will be assessed throughout the study for all patients. Information 
recorded will include start and stop dates and times, dose, frequency, route of administration, and 
indication. 
3.8.7 
Protocol Deviation Reporting 
A protocol deviation is defined as any intentional or unintentional change to, or noncompliance 
with, the approved protocol procedures or requirements. Deviations may result from the action or 
inaction of the subject or investigator. 
The following lists of protocol deviations of data may include the following: 
Data deviations (captured in the database): 
• The patient does not meet the protocol inclusion or exclusion criteria. 
• Failure to comply with dispensing or dosing requirements (eg, dosing not administered 
within the timeframe specified in the protocol 
• Missed visits 
• Test requirements, including vital signs, lab tests, physical assessments, PK blood draws, 
and medical history not followed – either tests not done, incorrect tests done, or not done 
within the timeframe specified in the protocol 
• Failure to obtain consent prior to beginning the study 
• The patient is noncompliant with the protocol, defined as failure to perform any portion 
of scheduled assessments or procedures 
Major deviations leading to exclusion from PK population: 
• PK data collected during the affected treatment period will be excluded from the study 
results.   
• Inaccurate dosing on the day of PK sampling. 
• Missed blood sample or deviations from blood collection times. 
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Major deviations leading to exclusion from EAS: 
• Patients with missing or incomplete/unreadable Day 28 EEG data. 
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4 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSIS 
There are no changes in the study conduct or analysis plans relative to the study protocol. 
 
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5 
QUALITY CONTROL AND QUALITY ASSURANCE METHODS FOR DATA 
ANALYSIS 
Case report forms will be monitored and collected by ICON. All monitored eCRFs will be sent 
to the Data Management group at ICON and processed according to the ICON Study Specific 
Procedure SSP DM-45080001.01 Data Management Plan (DMP). The DMP describes eCRF 
data processing, edit checks, data query management, medical dictionary coding, SAE 
reconciliation, data transfers, and data quality review through database lock or any necessary 
reopening of the database. After database lock, the data will be retrieved from the database using 
SAS® 9.4 or higher version.  
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6 
PHARMACOKINETIC AND EFFICACY ASSESSMENTS 
6.1 
Pharmacokinetic Assessments 
6.1.1 
Pharmacokinetic Analysis 
Pharmacokinetic analyses will be based on the PK population. 
Plasma PK concentrations for the investigational product will be presented in a data listing and 
summarized in tabular and graphical formats, as data allow. Overlay individual concentration-
time plasma PK profiles may also be presented.  
Population PK analysis using non-linear mixed-effects modelling will be performed given the 
sparse nature of the PK sampling.  Appropriate PK exposure metrics will be derived from the 
population PK model (AUC, Cmin and Cmax).  The relationship between plasma investigational 
product levels/exposure metrics and response will be explored graphically and a formal 
exposure-response model may be developed. 
A separate Modelling & Simulation Analysis Plan will be prepared to describe the data and 
methods to be used in the population PK analysis. The analysis will be performed using 
NONMEM v7.4 or higher version. The results of the population PK analysis will be reported 
separately to the CSR. 
6.2 
Efficacy Assessments 
Efficacy endpoints will include the following parameters: EEG, seizure diary and CGI-C. 
6.2.1 
Electroencephalogram 
A 16-hour overnight video-EEG will be performed at screening and Day 28 of Treatment Period 
1 to look for changes from baseline
 
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. 
6.2.2 
Seizure Diary  
The patient’s legal representative (parent[s]/caregiver[s]) will be provided with a seizure diary at 
the Screening Period visit (Visit 1) to record the number of seizures daily starting from the day 
after Visit 1 until the patient discontinues the investigational product. The seizure diaries for 
each patient will be assessed at Screening, Day 1, Day 2 to 6, Day 7, Day 12 or 13 or 14, Day 21 
and 28 of Treatment Period 1, and Day 42 of Treatment Period 2. 
The investigator will ensure that the seizure diary is being completed. The investigator will also 
review seizure counts to ensure the number of seizures is not increasing. The seizure diaries will 
indicate whether spasms are still present. 
 
6.2.3 
Clinical Global Impression of Change 
The CGI-C assessment will be collected from both the investigator and the parent/caregiver on 
Day 1, Day 7, Day 21 and Day 28 of Treatment Period 1 and Day 42 of Treatment Period 2. The 
CGI-C is a validated instrument that allows the investigator to rate the change in a patient’s 
condition on a 7-point scale ranging from “very much improved since the initiation of treatment” 
to “very much worse since the initiation of treatment.”
 
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Table 6-1 Clinical Global Impression of Change Scale 
Scale # 
Impression 
1 
very much improved 
2 
much improved 
3 
minimally improved 
4 
no change 
5 
minimally worse 
6 
much worse 
7 
very much worse 
 
 
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7 
STATISTICAL METHODS 
7.1 
General 
All statistical analysis will be conducted following the principles specified in the International 
Conference on Harmonization (ICH) Topic E9 Statistical Principles for Clinical Trials 
(CPMP/ICH/363/96). 
All statistical analyses will be performed using the statistical software SAS, Version 9.4 or newer 
and any exceptions will be detailed in the CSR.     
All results collected in the database will be presented in listings. Both absolute values and 
change-from-baseline values for each subject will be given where applicable. All continuous data 
will be listed with the same precision as presented in the database. Data listings will be sorted by 
subject ID, and time point.  
Unless otherwise noted, continuous variables will be summarized using the number of 
non-missing observations (n), arithmetic mean (mean), standard deviation (SD), median, 
minimum, maximum, Quartile 1 (Q1), and Quartile 3 (Q3); categorical variables will be 
summarized using the frequency count and the percentage of subjects in each category. Time to 
event data will be summarized using median, 25%, and 75% percentiles. 
In the data listings, study day relative to first dose of treatment may be presented. Study day 
relative to first dose will be calculated as: event date – first dose date (+1 if event date ≥ first 
dose date). 
Baseline will be the last non-missing available measurement prior to first dose of the study drug.  
For safety summaries, the unscheduled and repeat assessments will not be summarized; however, 
all results will be included in the data listings. 
All PK parameters will be summarized by the overall treatment group using descriptive statistics 
to include, as appropriate, n, mean, SD, coefficient of variation (CV), minimum, median, 
maximum, geometric mean (GM), and geometric CV.  
Disposition, demographics and baseline characteristics, all safety parameters and adverse events 
will be summarized overall.  
7.2 
Handling of Dropouts or Missing Data 
Missing data will not be imputed.  
7.2.1 
Handling of incomplete dates for AE 
Imputation rules for missing or partial AE start date are defined below: 
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If only Day of AE start date is missing:  
If the start date has month and year but day is missing, the first day of the month will be imputed 
• If this date is earlier than the first dose date, then the first dose date will be used instead. 
• If this date is later than the stop date (possibly imputed), then the stop date will be used 
instead. 
If Day and Month of AE start date are missing: 
If the start date has year, but day and month are missing, the 1st of January will be imputed 
• If this date is earlier than the first dose date, then the first dose date will be used instead. 
• If this date is later than the stop date (possibly imputed), then the stop date will be used 
instead. 
If Year of AE start date is missing: 
If the year of AE start is missing or AE start date is completely missing then query site with no 
imputation. Also compare the full (or partial) AE end date to the first dose date. If the AE end date 
is before the first dose date then the AE should be considered as a pre-treatment AE. Otherwise, 
the AE will be considered as TEAE. 
7.2.2 
Handling missing or partial Prior/Concomitant Medication Dates 
Missing or partial medication start date: 
a. If only DAY is missing, the first day of the month will be assumed.  
b. If DAY and Month are both missing, the first day of the year will be assumed.  
c. If DAY, Month and Year are all missing, the day before the first dose date will be 
assumed. 
Missing or partial medication stop date: 
a. If only DAY is missing, the last day of the month will be assumed. 
b. If DAY and Month are both missing, the last day of the year will be assumed. 
c. If DAY, Month and year are all missing, ‘continuing’ status to stop date will be 
assigned. 
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7.3 
Examination of Subgroups 
Additional subgroup summaries will be performed to determine whether differences exist in 
primary safety and efficacy endpoint results between subgroups.  
The list of potential subgroups (with applicable definitions in parentheses) includes, but is not 
necessarily limited to, the following: 
• Sex (Female vs. Male) 
• Age (6-12 months; >12-24 months; >24-36 months) 
• Concomitant anti-epileptic drugs (AEDs) (Specific categories to be finalized prior to 
database lock. The categories will be determined based upon which AEDs or 
combinations of AEDs the subjects take during the course of the study) 
For each subgroup variable, the frequency and percentage will be displayed. 
7.4 
Analysis Populations 
The following populations will be analyzed for overall treatment group (JBPOS0101): 
• All Enrolled Population: The Enrolled Population will include all patients who signed 
informed consent. 
• Safety Population: The safety population will include all patients who were treated with at 
least one dose of the investigational product. The safety population will be used for all safety 
assessments. 
• Efficacy Population (EAS): The efficacy population will include all patients, without any 
major protocol deviation affecting the efficacy endpoint analysis, who were treated with the 
investigational product for at least 26 days and completed the Day 28 (Visit 5 [± 2 days]) 
overnight video-EEG. The EAS will be used for all efficacy assessments. 
• Modified Efficacy Population (mEAS): To evaluate the influence of COVID-19 on the 
efficacy results, a modified EAS will be considered which, in addition to EAS population, 
includes also those patients with major protocol deviations affecting the efficacy endpoint 
analysis which can be attributed to COVID-19. The same efficacy analyses as for EAS 
population will also be performed for the mEAS population. 
• PK Population: The PK population will include all patients, without any major protocol 
deviation affecting the secondary endpoint analysis, who were treated with at least one dose 
of the investigational product and have at least one measurable PK concentration. The PK 
Population will be used for all PK assessments.  
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7.5 
Subject Accountability 
Summaries of analysis populations and subject disposition will be presented by overall treatment 
(JBPOS0101) and will contain the following information: 
 
• Number of subjects enrolled 
• Number and percent of subjects with screen failure 
• Number and percent of subjects with screen failure reason 
• Number and percent of subjects who were dosed 
 
• Number and percent of subjects who completed the study 
• Number and percent of subjects who discontinued early and reason for early 
discontinuation 
• Number and percent of subjects in the Safety, EAS, mEAS and PK Populations. 
This summary will be based on the All Enrolled Population. 
Subject disposition data, exclusions from the analysis populations, eligibility criteria satisfaction 
and consent information will be presented in listings. 
7.6 
Protocol Deviation Reporting 
Major protocol deviations will be identified prior to database lock and may include, but are not 
limited to, significant violations of inclusion/exclusion criteria, noncompliance with trial 
treatment taken, conditions such as vomiting and diarrhea or use of prohibited medications, and 
not following clinical trial protocol procedures. 
All Protocol deviations will be listed.  
7.7 
Subject Demographics and Baseline Characteristics 
Subject demographic data and baseline characteristics will be summarized using descriptive 
statistics by overall treatment and will include the following parameters: sex, age, race, ethnicity, 
concomitant anti-epileptic drugs, height, weight, and body mass index (BMI). Demographic data 
and baseline characteristics will also be listed for safety population. 
7.8 
Medical and Surgical History 
Medical and surgical history will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA, Version 22.0 or later) and listed. 
Medical history will be listed and summarized for safety population by System Organ Class 
(SOC) and Preferred Term (PT) for overall treatment. 
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7.9 
Extent of Exposure  
Exposure data will be presented in a listing and summarized by overall treatment. 
Total exposure [mg] of a patient will be defined as the cumulative dose of study drug that a 
patient received during the course of the study. The extent (duration) of exposure will be derived 
in days as Date of last dose – Date of first dose + 1.  
7.10 
Analysis of Exploratory Efficacy Data  
Exploratory Efficacy endpoints will be listed and summarized for following parameters: EEG, 
Seizure Diary and CGI-C.  
The same efficacy analyses as in the EAS will also be performed for the mEAS population. If 
both populations coincide (i.e., there are no major protocol violations attributable to COVID-19 
which affect the efficacy endpoint analysis) only the analyses in the EAS will be performed. 
7.10.1 
EEG 
Situations  
Date of censoring/event 
 
 
 
 
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In addition, the overall result of the video EGG at Day 28 (Visit 5 [± 2 days]) will be 
summarized for overall treatment.  
7.10.2 
Seizure Diary  
Seizure diary data will be presented in a listing and summarized by overall treatment for the 
following assessments and for the data captured in the eCRF under Seizure Diary Review Form:  
- 
Number of seizures 
- 
Seizure type 
7.10.3 
CGI-C 
CGI-C assessment will be listed and summarized by visit using descriptive statistics for overall 
treatment. 
7.11 
Analysis of Pharmacokinetic Data 
Concentrations data will be summarized in tables and figures when at least 3 subjects for overall 
treatment have non-missing data at the time point being summarized. Within individual subject 
concentration versus time profiles, whether graphical or tabular, all assayed concentrations will 
be presented, even when not summarized elsewhere. 
Concentration summaries and corresponding figures/listing will be presented using PK 
Population.  PK concentration data for blood and urine samples and volume of urine samples will 
be summarized for overall treatment by descriptive statistics of n, arithmetic mean, standard 
deviation (SD), coefficient of variation (CV), geometric mean, geometric CV, median, 
minimum, and maximum. Geometric CV is calculated as the square root of the exponentiated 
variance of the natural log transformed data minus 1 (SQRT (exp(SD2)-1)) where appropriate. 
 
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7.12 
Analysis of Safety Data 
7.12.1 
Adverse Events 
All AEs will be coded to SOC) and PT using Medical Dictionary for Regulatory Activities 
(Version 22.0 or later) and presented by subject in data listings. 
A treatment-emergent adverse event (TEAE) is defined as any AE that began or worsened 
following the start of dosing of Treatment Period 1, Day 1 to Follow-Up.  
A treatment-related AE is defined as any TEAE that is assessed by the Investigator as possibly, 
probably or definitely related to study drug. 
Adverse event analyses will be conducted using the Safety Population. 
The overall incidence of TEAEs (number and percentage of subjects) as well as the number of 
events will be summarized for mild TEAEs, moderate TEAEs, severe TEAEs, TEAEs assessed 
as at least possibly related, SAEs, TEAEs leading to study or drug discontinuation, SAEs related 
to study drug, life-threatening SAEs and SAEs resulting in death. All AE reports will also 
include the action taken as a result of the AE such as dose not changed, drug interrupted, drug 
withdrawn, dose increased, not applicable, or unknown.  
The following TEAEs summaries will be presented (where applicable the number of patients (%) 
and number of events will be summarized) by SOC and PT for overall treatment group:  
 
• TEAEs  
• Treatment-related TEAEs 
• TEAEs leading to investigational product discontinuation 
• Treatment-related TEAEs leading to investigational product discontinuation 
• Serious TEAEs 
• Treatment-related serious TEAEs 
• TEAEs leading to death 
• Treatment-related TEAEs leading to death. 
All TEAEs will be summarized by SOC and PT using frequency counts and percentages (i.e., 
number and percentage of patients with an event); also the number of events will be presented  
Tabulations will include an overall incidence of subjects reporting at least one AE, an overall 
incidence of TEAEs, and incidence within SOC and PT. Each patient may only contribute once 
(i.e., most severe occurrence) to each of the incidence rates, regardless of the number of 
occurrences. 
For the incidence at the subject level by SOC, PT and relationship to study drug; if a subject 
experiences more than 1 event within the same SOC and PT, only the most related occurrence (in 
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descending order of definitely related, probably related, and possibly related) will be included in 
the incidence. 
Listings of AEs, TEAEs, SAEs, TEAEs leading to death and TEAEs leading to study drug 
discontinuation will also be presented.  
7.12.2 
Clinical Laboratory Assessments 
Observed values and change from baseline for each parameter of continuous clinical laboratory 
values (hematology, coagulation, serum chemistry and urinalysis) will be summarized by overall 
and visit using descriptive statistics.  
Shift from screening/baseline to post-baseline laboratory findings in normal range criteria will 
also be summarized.  
A listing of all clinical laboratory data for each subject at each visit will be presented. Clinical 
laboratory values that are outside the normal ranges will be presented in a separate listing. The 
normal ranges will also be listed. 
7.12.3 
Vital Signs, Height, Weight, and Body Mass Index 
Observed values and change from baseline for each parameter of continuous vital sign 
parameters (blood pressure, temperature, pulse rate and respiratory rate) and height, weight, and 
BMI will be summarized by overall treatment and visit using descriptive statistics.  
All vital signs and height, weight, and BMI data will be listed individually by each subject. 
Abnormal values will be flagged in the listing. 
7.12.4 
Electrocardiograms 
Continuous ECG parameters including RR interval, PR interval, QRS width, QT interval, and 
QTcF interval will be summarized by overall treatment and scheduled timepoints in terms of 
absolute values and change from baseline using descriptive statistics. 
Shift tables will be presented that summarize the overall ECG interpretation as normal, abnormal 
not clinically significant, or abnormal clinically significant at baseline and each post-baseline 
time point. 
ECG data will be listed by subject at each visit and time point collected with indicated clinically 
significant results. 
ECG results meeting pre-specified criteria are listed and summarized. The following reference 
range ECG criteria by age range will be used. 
 
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Age Range 
ECG 
Parameters 
Lower Limit of 
Normal 
Upper Limit of 
Normal 
6-12 Months (including 12th  
Month) 
QT Interval  
381 msec 
449 msec 
QTcF Interval  
350 msec 
440 msec 
>12-24 Months 
QT Interval  
381 msec 
455 msec 
QTcF Interval  
350 msec 
440 msec 
>24-36 Months 
QT Interval  
381 msec 
455 msec 
QTcF Interval  
350 msec 
440 msec 
7.12.5 
Physical and Neurological Examinations 
Physical and neurological examination abnormalities will be listed.  
Shift tables will be presented that summarize the change in examination findings as normal, 
abnormal not clinically significant, or abnormal clinically significant at baseline and each post-
baseline visit. 
7.12.6 
Prior and Concomitant Medications 
Prior medications are defined as those medications that started and stopped prior to the first dose 
of study drug. Concomitant medications are defined as those medications with a start date on or 
after the first dose of study drug or started prior to the first dose of study drug and were 
continued after the first dose of study drug. 
Prior and concomitant medications are coded using World Health Organization Drug Dictionary 
(WHO Drug) (Version March 2019 or later) and classified according to anatomical therapeutic 
chemical code (ATC) levels 2 (therapeutic sublevel) and 3 (pharmacological sublevel).  Prior and 
concomitant medication data will be summarized and listed by ATC sublevels and preferred 
name. 
A separate listing will be provided for concomitant procedures.  
7.12.7 
COVID-19 
Impact of COVID-19 on various visits will be collected. This data will be listed and summarized 
for Safety Population. 
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7.13 
Sample Size 
 
Approximately 50 patients will be screened of which around 35 patients will be enrolled to 
provide at least 26 completers. At least 7 of the patients enrolled must be between 6 months 
through 12 months of age at the time of informed consent. Patients who are screened and not 
dosed will be replaced. Patients who discontinue the study for any reason after dosing will not be 
replaced. 
7.14 
Interim Analysis 
No interim analyses are planned. 
 
 
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7.15 
General Conventions for Tables, Listings and Figures  
For summary tables, unless otherwise specified, the number of decimal places provided in the 
SAS output will be based on the accuracy of the least accurate value in the raw data as follows: 
n 
integer 
Arithmetic mean 
1 decimal place more than the least accurate number in the raw data 
SD 
2 decimal place more than the least accurate number in the raw data 
CV 
2 decimal places 
Geometric mean 
1 decimal place more than the least accurate number in the raw data 
Geometric CV               2 decimal places  
Median 
1 decimal place more than the least accurate number in the raw data 
Minimum 
same number of decimal places as raw data 
Maximum 
same number of decimal places as raw data 
Q1                                  same number of decimal places as raw data 
Q3 
same number of decimal places as raw data 
Confidence interval  
same number of decimals as the associated statistic 
Percentage 
1 decimal place 
 
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8 
TABLES, FIGURES, AND LISTINGS 
Table/Figure Number 
Table/Figure Name 
Section 14.1 
Demographic and Subject Characteristics Data Summaries 
Table 14.1.1 
Summary of Subject Disposition (All Enrolled Population) 
Table 14.1.2 
Analysis Populations (All Enrolled Population) 
Table 14.1.3 
Summary of Demographic and Baseline Characteristics (Safety 
Population) 
Table 14.1.4 
Summary of Medical History (Safety Population) 
Table 14.1.5 
Summary of Prior & Concomitant Medications  (Safety 
Population) 
Table 14.1.6 
Summary of Exposure  (Safety Population) 
Section 14.2 
Pharmacokinetic and Efficacy Data Summaries 
Table 14.2.1.1 
Summary of Electroencephalogram Responses (EAS Population) 
Table 14.2.1.2 
Summary of Electroencephalogram Responses (mEAS 
Population) 
Table 14.2.2.1 
Descriptive Summary for Time to Relapse, Resolution of  
Spasms and Hypsarrhythmia during Dose Tapering Period (EAS 
Population) 
Table 14.2.2.2 
Descriptive Summary for Time to Relapse, Resolution of  
Spasms and Hypsarrhythmia during Dose Tapering Period 
(mEAS Population) 
Table 14.2.3.1.1 
Summary of Seizure Diary Card (EAS Population) 
Table 14.2.3.1.2 
Summary of Seizure Diary Card (mEAS Population) 
Table 14.2.3.2.1 
Summary of Seizure Diary Review (EAS Population) 
Table 14.2.3.2.2 
Summary of Seizure Diary Review (mEAS Population) 
Table 14.2.4.1 
Summary of CGI-C Assessments Results (EAS Population) 
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Table 14.2.4.2 
Summary of CGI-C Assessments Results (mEAS Population) 
Table 14.2.5 
Summary of Pharmacokinetic Plasma JBPOS0101 Concentrations 
(PK population) 
Table 14.2.6 
Summary of Pharmacokinetic Urine JBPOS0101 Concentrations 
(PK population) 
Table 14.2.7 
Summary of Urine Volume (PK population) 
Figure 14.2.1 
Mean (+SD) Plasma JBPOS0101 Concentrations vs Time for Day 
1 (PK Population) (Note: Present in linear and semi-log scales.) 
Figure 14.2.2 
Mean (+SD) Plasma JBPOS0101 Concentrations vs Time for Day 
21 (PK Population) (Note: Present in linear and semi-log scales.) 
Section 14.3 
Safety Data Summaries 
Section 14.3.1 
Displays of Adverse Events 
Table 14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events (Safety 
Population) 
Table 14.3.1.2 
Summary of TEAEs by System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.3 
Summary of Treatment-Related TEAEs by System Organ Class 
and Preferred Term (Safety Population) 
Table 14.3.1.4 
Summary of TEAEs Leading to Investigational Product 
Discontinuation by System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.5 
Summary of Treatment-Related TEAEs leading to investigational 
product discontinuation by System Organ Class and Preferred 
Term (Safety Population) 
Table 14.3.1.6 
Summary of Serious TEAEs by System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.7 
Summary of Treatment-Related Serious TEAEs by System Organ 
Class and Preferred Term (Safety Population) 
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Protocol No. CL-0101-WS01 
ICON Project No. 4508-0001 
Statistical Analysis Plan 
05 Mar 2021
 
 
CONFIDENTIAL 
Page 43 of 45 
 
Table 14.3.1.8 
Summary of TEAEs Leading to Death by System Organ Class 
and Preferred Term (Safety Population) 
Table 14.3.1.9 
Summary of Treatment-related TEAEs Leading to Death by 
System Organ Class and Preferred Term (Safety Population) 
Section 14.3.2 
Listings of Deaths, Other Serious and Certain Significant 
Adverse Events 
Table 14.3.2.1 
Listing of Deaths, Other Serious Adverse Events, and Significant 
Adverse Events (Safety Population) 
Section 14.3.4 
Laboratory Summaries 
Table 14.3.4.1 
Listing of Abnormal Laboratory Results (Safety Population) 
Table 14.3.4.2 
Observed and Change from Baseline for Clinical Laboratory 
Parameters (Safety Population) 
Table 14.3.4.3 
Shift Assessment of Categorical Change of Laboratory Results 
from Baseline to each Post-Baseline Visit (Safety Population) 
Section 14.3.5 
Additional Safety Data Summaries 
Table 14.3.5.1 
Observed and Change from Baseline Vital Signs, Height, Weight, 
and Body Mass Index (Safety Population) 
Table 14.3.5.2 
Observed and Change from Baseline ECG (Safety Population) 
Table 14.3.5.3  
Shift Assessment of Overall ECG Interpretation at Baseline and 
Each Post-Baseline Time-point (Safety Population) 
Table 14.3.5.4  
Shift Assessment of Physical and Neurological Examination at 
Baseline and Each Post-Baseline Time-point (Safety Population) 
Table 14.3.5.5 
Summary of COVID-19 Data (Safety Population) 
Listing Number 
Listing Name 
Section 16.2.1 
Discontinued Subjects 
Listing 16.2.1 
Subject Disposition (All Enrolled Population) 
Section 16.2.2 
Protocol Deviations 
DocUUID : f75a4a78-cab2-46a6-8fc6-9df6b9a58ff3


 
Bio-Pharm Solutions Co., Ltd. 
Protocol No. CL-0101-WS01 
ICON Project No. 4508-0001 
Statistical Analysis Plan 
05 Mar 2021
 
 
CONFIDENTIAL 
Page 44 of 45 
 
Listing 16.2.2 
Protocol Deviations (Safety Population) 
Section 16.2.3 
Subjects Excluded from Analysis 
Listing 16.2.3 
Exclusions from Analysis Populations (All Enrolled Population) 
Section 16.2.4 
Demographic Data 
Listing 16.2.4.1 
Demographics and Baseline Characteristics (Safety Population) 
Listing 16.2.4.2 
Eligibility Criteria Satisfaction (All Enrolled Population) 
Listing 16.2.4.3 
Consent Information (All Enrolled Population) 
Listing 16.2.4.4 
Medical History (Safety Population) 
Listing 16.2.4.5 
Prior and Concomitant Medications (Safety Population) 
Listing 16.2.4.6 
Concomitant Procedures (Safety Population) 
Section 16.2.5 
Compliance and/or Drug Concentration Data 
Listing 16.2.5.1 
Study Drug Dosing Record (Safety Population) 
Listing 16.2.5.2 
Individual Plasma JBPOS0101 Concentrations (PK Population)  
Listing 16.2.5.3 
Individual Urine JBPOS0101 Concentrations (PK Population)  
Figure 16.2.5.1 
Individual Plasma JBPOS0101 Concentrations vs Time for Day 1 
(PK Population) (For each subject, present the individual 
concentration in linear and semi-log scale.)  
Figure 16.2.5.2 
Individual Plasma JBPOS0101 Concentrations vs Time for Day 
21 (PK Population) (For each subject, present the individual 
concentration in linear and semi-log scale.)  
Section 16.2.6 
Individual Pharmacokinetic and Efficacy Response Data 
Listing 16.2.6.1 
EEG Responses (EAS Population) 
Listing 16.2.6.2 
Seizure Diary Responses (EAS Population) 
Listing 16.2.6.3 
CGI-C Assessment Results (EAS Population) 
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Bio-Pharm Solutions Co., Ltd. 
Protocol No. CL-0101-WS01 
ICON Project No. 4508-0001 
Statistical Analysis Plan 
05 Mar 2021
 
 
CONFIDENTIAL 
Page 45 of 45 
 
Section 16.2.7 
Adverse Event Listings 
Listing 16.2.7.1 
All Adverse Events (Safety Population) 
Listing 16.2.7.2 
Serious Treatment-Emergent Adverse Events by Subject (Safety 
Population) 
Listing 16.2.7.3 
Treatment-Emergent Adverse Events Leading to Discontinuation 
of Study Drug by Subject (Safety Population) 
Listing 16.2.7.4 
Treatment-Emergent Adverse Events Leading to Death by Subject 
(Safety Population) 
Section 16.2.8 
Individual Laboratory Measurements by Subject 
Listing 16.2.8.1 
Normal Ranges for Laboratory Data 
Listing 16.2.8.2 
Clinical Laboratory Data by Category (Safety Population) 
Listing 16.2.8.3.1 
Vital Signs (Safety Population) 
Listing 16.2.8.3.2 
Weight, Height and BMI (Safety Population) 
Listing 16.2.8.4 
Electrocardiogram Results (Safety Population) 
Listing 16.2.8.5 
Electrocardiogram Results Meeting Prespecified Criteria (Safety 
Population) 
Listing 16.2.8.6 
Physical and Neurological Examination Findings (Safety 
Population) 
Listing 16.2.8.7 
COVID-19 Data (Safety Population) 
Section 16.2.9 
General Comments 
Listing 16.2.9.1 
Investigator Comments (Safety Population) 
 
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