Clinical trial NCT04139122
Conditions: Dry Eye Disease Dry Eye Syndrome
Sponsor: Senju Pharmaceutical Co., Ltd.
Start date: 2019-10-05; Completion date: 2020-03-03
Enrollment: 89 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is the first study in humans to evaluate the effectiveness of SJP-0132 in the treatment of dry eye disease. This study will evaluate the safety, tolerability, efficacy, and pharmacokinetics of single- and multiple-dose regimens of SJP-0132 in subjects with dry eye disease

Detailed description:

Arms: arm 1: Each cohort will receive a single dose of 1 of 4 strengths of SJP-0132 arm 2: Single dose of placebo arm 3: Cohort 5 SJP-0132 will receive the second maximum acceptable dose from Cohorts 1-4 for 4 weeks. Cohort 6 SJP-0132 will receive the maximum acceptable dose from Cohorts 1-4 for 4 weeks arm 4: Multiple dose placebo for 4 weeks
Interventions: intervention 1: SJP-0132 intervention 2: Placebo
Intervention descriptions: intervention 1: SJP-0132 is administered as an eye drop intervention 2: Placebo is administered as an eye drop

Protocol documents:
Prot_SAP_001.pdf: 
 
 
 
NCT Number: NCT04139122 
 
 
Protocol Number: SJP-0132/1-01 
 
 
Study Title: 
A Randomized, Double-Masked, Single-Center, Placebo-Controlled Single and 
Multiple Ascending Dose Study to Assess Safety, Tolerability, Pharmacokinetics, 
and Efficacy of SJP-0132 in Subjects with Dry Eye Disease 
 
 
Protocol Version: Version 3.0: 12 December, 2019 
 
 














CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 7 of 75 
Status: Final v3.0; Date 12Dec2019 
Protocol Amendment Summary of Changes Table 
DOCUMENT HISTORY 
Document 
Date 
Amendment 1 (Protocol Version 3.0) 
12 Dec 2019 
Revision (Protocol Version 2.0) 
21 Aug 2019 
Original Protocol (Protocol Version 1.0) 
29 July 2019 
 
Amendment 1 (12 Dec 2019) 
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because it neither significantly impacts the safety or physical integrity of participants nor the 
scientific value of the study. 
Overall Rationale for the Amendment: 
The timing of some of the End-of-Study assessments for Part B was modified. 
Section # and 
Name 
Description of Change 
Brief Rationale 
2, Schedule of 
Activities, Part B, 
EOS 
Shifted hematology, serum chemistry, 
urinalysis, and serum pregnancy test to 2h 
postdose. 
Shifted physical examination, weight, and 
vital signs to 4h postdose. 
Shifted visual acuity (Snellen), slit lamp 
biomicroscopy w/out mydriatics, Schirmer 
I w/o anesthesia, intraocular pressure, slit 
lamp biomicroscopy w/ mydriatics (lens 
observation), and ophthalmoscopy to 8h 
postdose. 
 
Adjustments to timing of 
assessments to occur after 
dosing. 
9, Study 
Assessments and 
Procedures, Part 
B, Day 29 ±2, 
EOS 
Timing of assessments modified according 
to Schedule of Activities 
Consistency 
Revision 1 (21 Aug 2019) 
Minor editorial changes only. This version was submitted to the US Food and Drug 
Administration. 


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 8 of 75 
Status: Final v3.0; Date 12Dec2019 
Table of Contents 
 
STUDY ADMINISTRATION.....................................................................5 
Protocol Amendment Summary of Changes Table .....................................7 
Table of Contents .........................................................................................8 
1. 
Synopsis......................................................................................11 
2. 
Schedule of Activities (SoA) .....................................................16 
3. 
Introduction ...............................................................................20 
3.1. 
Study Rationale ...........................................................................22 
3.2. 
Background .................................................................................22 
3.2.1. 
Nonclinical Studies .....................................................................22 
3.2.2. 
Clinical Studies ...........................................................................25 
3.2.3. 
Efficacy .......................................................................................26 
3.2.4. 
Safety ..........................................................................................26 
3.3. 
Benefit/Risk Assessment ............................................................26 
4. 
Objectives and Endpoints ........................................................28 
5. 
Study Design ..............................................................................29 
5.1. 
Overall Design ............................................................................29 
5.2. 
Subject and Study Completion ...................................................30 
5.3. 
End of Study Definition ..............................................................30 
5.4. 
Scientific Rationale for Study Design ........................................31 
5.5. 
Justification for Dose ..................................................................31 
6. 
Study Population .......................................................................32 
6.1. 
Inclusion Criteria ........................................................................32 
6.2. 
Exclusion Criteria .......................................................................32 
6.3. 
Lifestyle Restrictions ..................................................................34 
6.3.1. 
Meals and Dietary Restrictions ...................................................34 
6.3.2. 
Caffeine, Alcohol, and Tobacco .................................................34 
6.3.3. 
Activity .......................................................................................34 
6.4. 
Screen Failures ............................................................................34 
7. 
Treatments .................................................................................35 
7.1. 
Treatments Administered ............................................................35 
7.2. 
Investigational Product Information ...........................................35 
7.3. 
Preparation/Handling/Storage/Accountability ............................35 
7.4. 
Dose Modification ......................................................................35 
7.5. 
Method of Treatment Assignment ..............................................36 
7.6. 
Masking ......................................................................................36 
7.7. 
Missed Doses ..............................................................................37 
7.8. 
Concomitant Therapy .................................................................37 
7.8.1. 
Recording Prior and Concomitant Medications ..........................37 
7.8.2. 
Prohibited Concomitant Medications, Treatments, and 
Procedures ...................................................................................37 


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 9 of 75 
Status: Final v3.0; Date 12Dec2019 
7.8.3. 
Rescue Medicine .........................................................................37 
7.9. 
Treatment after the End of the Study ..........................................37 
8. 
Discontinuation/Withdrawal Criteria .....................................38 
8.1. 
Discontinuation of Study Treatment ...........................................38 
8.2. 
Withdrawal from the Study.........................................................38 
8.3. 
Lost to Follow Up .......................................................................39 
9. 
Study Assessments and Procedures.........................................40 
9.1. 
Efficacy Assessments .................................................................50 
9.2. 
Safety Assessments .....................................................................51 
9.2.1. 
Ocular Safety ..............................................................................51 
9.2.2. 
Physical Examinations ................................................................52 
9.2.3. 
Vital Signs ...................................................................................52 
9.2.4. 
Clinical Safety Laboratory Assessments ....................................53 
9.3. 
Adverse Events ...........................................................................53 
9.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .................................................................................53 
9.3.2. 
Method of Detecting AEs and SAEs ..........................................54 
9.3.3. 
Follow-up of AEs and SAEs .......................................................54 
9.3.4. 
Regulatory Reporting Requirements for SAEs ...........................54 
9.3.5. 
Pregnancy ....................................................................................54 
9.4. 
Treatment of Overdose ...............................................................55 
9.5. 
Pharmacokinetics ........................................................................55 
9.6. 
Health Economics .......................................................................56 
10. 
Statistical Considerations .........................................................56 
10.1. 
General Considerations ...............................................................56 
10.2. 
Sample Size Determination ........................................................56 
10.3. 
Populations for Analyses ............................................................57 
10.4. 
Statistical Analyses .....................................................................57 
10.4.1. Efficacy Analyses .......................................................................58 
10.4.2. Safety Analyses ...........................................................................59 
10.4.3. Pharmacokinetic Analyses ..........................................................59 
11. 
References ..................................................................................60 
12. 
Appendices .................................................................................61 
Appendix 1: Abbreviations and Terms ......................................................61 
Appendix 2: Clinical Laboratory Tests ......................................................63 
Appendix 3: Study Governance Considerations ........................................64 
Appendix 4: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................67 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................73 
  


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 10 of 75 
Status: Final v3.0; Date 12Dec2019 
In-Text Tables 
Table 9-1: Volume of Blood to be Collected from Each Subject .........40 
 










CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 15 of 75 
Status: Final v3.0; Date 12Dec2019 
Statistical Methods 
The primary statistical analysis of the data will be descriptive in nature. For continuous variables 
this means calculation of the number of observations, mean, standard deviation, median, 
minimum, and maximum. Categorical variables will be summarized by subject counts and 
related percentages. For ordinal-scaled variables, a combination of the above may be employed 
as appropriate: frequency and percentage of observations within a category and means and 
standard deviations of the scores of the categories. For categorical and ordinal variables, 
percentages will be calculated based on non-missing data. 
Sample Size Determination: 
No formal sample size and/or power calculations were performed for the study, however a sample 
size was chosen based on feasibility to allow total of 92 randomized subjects for Part A (n=32) 
and Part B (n=60). Approximately 32 subjects are expected to complete Part A and 60 subjects are 
expected to complete Part B. 
Safety Analysis: 
Safety assessments and changes from baseline in vital signs, clinical laboratory results, adverse 
events (AEs), will be summarized using descriptive statistics (mean, standard deviation, 
coefficient of variation (%CV), median, minimum, and maximum). Concomitant medications and 
physical examination findings will be listed.  
Efficacy Analysis: 
The study eye will be the eye with the greater central zone corneal fluorescein staining. If both 
eyes meet all of the inclusion and none of the exclusion criteria and the central zone corneal 
fluorescein staining scores are equal, the right eye (OD) will be designated as the study eye for the 
duration of this study.  
The fellow eye (non-study eye) will be treated with the product as per the assigned dosing 
schedule. 
Change in eye assessments will be summarized using descriptive statistics (mean, standard 
deviation, coefficient of variation (%CV), median, minimum, and maximum). The primary 
endpoint is the difference between SJP-0132 and placebo in changes in eye dryness symptom 
(visual analog scale [VAS]). Secondary endpoints are changes in dry eye signs (vital staining of 
cornea, conjunctiva and lid margin, tear film break-up time (TFBUT), and changes in dry eye 
symptoms (VAS [ie, severity of eye dryness, discomfort, burning/stinging, sticky feeling, foreign 
body sensation, itching, pain, blurred vision, and sensitivity to light], ocular surface disease index 
[OSDI], Dry eye Questionnaire 5 [DEQ-5] scores). 
Pharmacokinetic Analysis: 
Plasma samples will be analyzed to determine the concentration of SJP-0132. Pharmacokinetic 
variables will be calculated using non-compartmental analysis. Part A: Cmax, tmax, tlast, AUC0-last, 
AUC0-∞, AUC%extrap, t1/2, AUMC0-last, AUMC0-∞, MRT0-last, MRT0-∞, Vd/F, CL/F, Cmax,norm, 
AUC0-last,norm, AUC0-∞,norm. Part B: Cmax, tmax, tlast, AUC0-last, Cmax,norm, and AUC0-last,norm on Day 1, 
Ctrough on Days 2, 4 and 8, and Rac. The PK data will be summarized using descriptive statistics 
and will also be displayed graphically as appropriate. 


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 16 of 75 
Status: Final v3.0; Date 12Dec2019 
2. 
Schedule of Activities (SoA) 
Part A (SAD) 
Screen 
Run-in 
Check 
In 
Treatment Phase 
Check 
Out 
Procedure 
All 0h assessments will be performed prior 
to Drug administration. 
Day -30  
to  
Day -15 
Day -14 
(+2)5 
to  
Day -2 
Day -1 
Day 1 
Day 2 
0 h 
0.25 h 
0.5 h 
1 h 
2 h 
4 h 
8 h 
12 h 
0 h 
Informed Consent / HIPAA 
X 
  
  
  
  
  
  
  
  
  
  
  
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical / Surgical History 
X 
  
 X 
   
  
  
  
  
  
  
  
  
Inclusion/Exclusion Criteria 
X 
  
 X 
   
  
  
  
  
  
  
  
  
Physical Examination1 
X 
  
  
X 
  
  
X 
  
  
  
  
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
X 
 
 
 
 
 
 
 
 
 
Vital signs2 
X 
  
 X 
X 
  
X 
X 
X 
X 
X 
X 
X 
DEQ-5 3 
X 
  
X 
   
  
  
  
  
  
  
  
  
VAS 3 
X 
  
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
OSDI© 3 
X 
  
X 
  
  
  
  
  
  
  
  
  
Hematology, Serum Chemistry, Urinalysis 
X 
  
 X 
   
  
  
  
  
  
  
  
X 
Serology (HIV, HBsAg, HCV) 
X 
  
  
   
  
  
  
  
  
  
  
  
Serum pregnancy test and FSH (WOCBP only) 
X 
  
  
   
  
  
  
  
  
  
  
  
Pharmacokinetic Sampling  
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine drug and alcohol screen 
X 
  
 X 
   
  
  
  
  
  
  
  
  
Urine Pregnancy Test 
  
  
 X 
   
  
  
  
  
  
  
  
  
Visual Acuity (Snellen) 
X 
  
X 
  
  
  
  
  
  
  
X 
X 
Slit lamp biomicroscopy (w/out mydriatics) 
X 
  
  
X 
  
  
X 
X 
  
  
X 
X 
Matrix Metalloproteinase-9 (MMP-9)4 
X 
  
X 
  
  
  
  
  
  
  
  
  
TFBUT 
X 
  
  
X 
  
  
 
X 
  
  
X 
X 
Corneal fluorescein staining (Baylor) 
X 
  
X 
X 
  
  
 
X 
  
  
X 
X 
Lissamine green staining (Baylor + Lid Margin) 
X 
  
  
X 
  
  
  
  
  
  
  
  
Aesthesiometer 
X 
  
 
 
 
 
 
 
 
 
 
 
Schirmer I w/o anesthesia 
X 
  
X 
   
  
  
  
  
  
  
X 
X 
VAS w/ anesthesia 
X 
  
  
  
  
  
  
  
  
  
  
  
Intraocular Pressure (iCare tonometer) 
X 
  
  
X 
  
  
  
X 
  
  
X 
X 
Slit lamp biomicroscopy (w/ mydriatics; lens 
observation) 
X 
  
X 
  
  
  
  
  
  
  
X 
X 
Ophthalmoscopy 
X 
  
X 
  
  
  
  
  
  
  
X 
X 
Record and assess adverse events 
 
Continuous 
Concomitant Medications 
 
Continuous 
Confinement Period 
  
X 
Randomization 
  
  
  
X 
  
  
  
  
  
  
  
  
Drug Administration 
  
Placebo6 
Placebo6 
X 
  
  
  
  
  
  
  
  
HIPAA = Health Information Portability and Accountability Act; VAS = Visual Analog Scale; TFBUT = Tear film break-up time; OSDI = Ocular 
Surface Disease Index; WOCBP = women of child-bearing potential 
1 Physical Examination includes head-eye-ears-nose-throat, cardiovascular, respiratory, gastrointestinal, dermatologic, and neurologic examinations.  
2 Blood pressure, heart rate, respiratory rate, oral temperature. 
 
 
 
 
 
 
 
 
 
 
 
3 Questionnaires will be completed prior to lab or PK timepoints. Ophthalmic assessments will follow lab or PK timepoints. 
4 30 minutes before staining tests 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 Day -14 can be completed within +2 days (Day -14 to Day -16), however Placebo Run-In dosing will begin on Day -14 per protocol 
6 For Placebo Run-In (Day -14 visit) subjects will be dispensed placebo and educated in administration and dosing diary completion. 


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 17 of 75 
Status: Final v3.0; Date 12Dec2019 
Part B (MAD) (3 pages) 
Screen 
Run-In 
Check In 
Treatment Period 
Procedure 
All 0h assessments will be performed prior to 
Drug administration. 
Day -30 
to 
Day -15 
Day -14 
(+2)5  
to 
Day -2 
Day –1 
Day 1 
Day 2 
Day 3 
0 h 
0.25 h 
0.5 h 
1 h 
2 h 
4 h 
8 h 
12 h 
0 h 
4 h 
8 h 
12 h 
0 h 
4 h 
8 h 
12 h 
Informed Consent/HIPAA  
X 
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/Surgical history 
X 
  
X 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
Inclusion/Exclusion Criteria 
X 
  
X 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
Physical examinations1 
X 
  
  
 X 
  
  
X 
  
  
  
  
X 
  
  
  
X 
  
  
  
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs2 
X 
  
X 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DEQ-5 3 
X 
  
X 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
VAS 3  
X 
  
X 
X  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
OSDI© 3 
X 
  
X 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
 
Hematology, Serum Chemistry, Urinalysis 
X 
  
X 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
Serology (HIV, HBsAg, HCV) 
X 
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
Serum pregnancy test and FSH (WOCBP only) 
X 
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
Pharmacokinetic Sampling 
  
  
  
X  
X 
X 
X 
X 
X 
  
  
X 
  
  
  
  
  
  
  
Urine drug and alcohol screen  
X 
  
X 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
Urine pregnancy test 
  
  
X 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
Visual acuity (Snellen) 
X 
  
X 
  
  
  
  
  
  
  
X 
X 
  
  
  
X 
  
  
 
Slit lamp biomicroscopy (w/out mydriatics)  
X 
  
  
 X 
  
  
X 
X 
  
 
X 
X 
  
  
X 
X 
  
  
X 
Matrix Metalloproteinase-9 (MMP-9)4 
X 
  
X 
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
TFBUT   
X 
  
  
X  
  
  
  
X 
  
 
X 
X 
  
  
X 
X 
  
  
X 
Corneal fluorescein staining (Baylor)  
X 
  
X 
X  
  
  
  
X 
  
 
X 
X 
  
  
X 
X 
  
  
X 
Lissamine green staining (Baylor +Lid Margin)  
X 
  
  
 X 
  
  
  
  
  
 
X 
X 
  
  
X 
X 
  
  
X 
Aesthesiometer  
X 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Schirmer I w/o anesthesia 
X 
  
X 
  
  
  
  
  
  
  
X 
X 
  
  
  
  
  
  
  
 VAS w/ anesthesia 
X 
  
  
   
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Intraocular pressure (iCare tonometer) 
X 
  
  
X  
  
  
  
  
  
  
X 
X 
  
  
  
X 
  
  
  
Slit lamp biomicroscopy (w/ mydriatics; lens 
observation) 
X 
  
X 
  
  
  
  
  
  
  
X 
 
  
  
  
  
  
  
  
Ophthalmoscopy 
X 
  
X 
  
  
  
  
  
  
  
X 
 
  
  
  
  
  
  
  
Record and assess adverse events  
  
Continuous 


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 18 of 75 
Status: Final v3.0; Date 12Dec2019 
Part B (MAD) (3 pages) 
Screen 
Run-In 
Check In 
Treatment Period 
Procedure 
All 0h assessments will be performed prior to 
Drug administration. 
Day -30 
to 
Day -15 
Day -14 
(+2)5  
to 
Day -2 
Day –1 
Day 1 
Day 2 
Day 3 
0 h 
0.25 h 
0.5 h 
1 h 
2 h 
4 h 
8 h 
12 h 
0 h 
4 h 
8 h 
12 h 
0 h 
4 h 
8 h 
12 h 
Concomitant medications  
  
Continuous 
Confinement Period 
  
  
Day -1 until Day 8 
Randomization 
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Drug administration 
  
Placebo6  
Placebo6  
X 
  
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HIPAA = Health Information Portability and Accountability Act; VAS = Visual Analog Scale; TFBUT = Tear film break-up time; OSDI = Ocular Surface Disease Index; WOCBP = women of 
childbearing potential; FSH = follicle stimulating hormone 
1 Physical Examination includes head-eye-ears-nose-throat, cardiovascular, respiratory, gastrointestinal, dermatologic, and neurologic examinations.  
2 Blood pressure, heart rate, respiratory rate, oral temperature.  
3 Questionnaires will be completed prior to lab or PK timepoints. Ophthalmic assessments will follow lab or PK timepoints. 
4 30 minutes before staining tests 
5Day -14 can be completed within +2 days (Day -14 to Day -16), however Placebo Run-In will begin on Day -14, per protocol 
6 For Placebo Run-In (Day -14 visit) subjects will be dispensed placebo and will be educated in self -administration and dosing diary completion. 
 
 


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 19 of 75 
Status: Final v3.0; Date 12Dec2019 
Part B (MAD) (3 Pages) 
Treatment Period (continued) 
EOS 
Follow 
Up 
Procedure 
All 0h assessments will be performed prior 
to Drug administration. 
Day 4 to Day 7 
Day 8 
(Check Out) 
Day 9 to  
Day 28 dosing 
Outpatient Visit  
Days 15±2, 22±2 
Day 29±2 
Day 
36±2 
0 h 
0.5 h
1h 
2h 
4h 
8h 
12h 
0 h  
4 h 
8 h 
12 h 
0 h  
4 h 
8 h 
12 h 
0 h 
4 h 
8 h 
12 h 
0 h  
2 h 
4 h 
8 h 
  
Physical examinations1 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
X 
  
  
  
 
  
X 
 
  
Weight 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Vital signs2 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
X 
 
 
 
 
 
X 
 
  
DEQ-5 3 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
X 
 
  
 
  
VAS3,4 
X 
X X 
X 
X  X  X 
X 
  
  
  
  
  
  
  
X 
X 
X 
 
X 
 
X 
X 
  
OSDI© 3 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
X 
  
  
  
X 
 
 
 
  
Hematology, Serum Chemistry, Urinalysis 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
 
X 
 
  
  
Serum pregnancy test (for WOCBP only) 
   
  
  
  
  
  
  
   
  
  
  
  
  
  
  
 
  
  
  
 
X 
 
  
  
Pharmacokinetic Sampling 
X5 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
  
Visual Acuity (Snellen) 
X 
  
  
  
  
  
 
X 
  
  
  
  
  
  
  
X 
  
  
 
 
 
  
X 
  
Slit lamp biomicroscopy w/out mydriatics  
X 
  
  
  
  
  
X 
X 
  
  
  
  
  
  
  
X 
  
  
  
 
 
 
X 
  
Matrix Metalloproteinase-9 (MMP-9)6 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
X 
  
  
  
  
TFBUT   
X 
  
 
 
  
  
X 
X 
  
  
  
  
  
  
  
X 
  
  
  
X 
  
  
  
  
Corneal fluorescein staining (Baylor)  
X 
  
 
 
  
  
X 
X 
  
  
  
  
  
  
  
X 
  
  
  
X 
  
  
  
  
Lissamine green staining (Baylor +Lid 
Margin)  
X 
  
 
 
  
  
X 
X 
  
  
  
  
  
  
  
X 
  
  
  
X 
  
  
  
  
Schirmer I w/o anesthesia 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
 
  
  
  
 
  
  
X 
  
Intraocular pressure (iCare tonometer) 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
X 
  
  
  
 
  
  
X 
  
Slit lamp biomicroscopy w/ mydriatics  
(lens observation)  
   
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
 
  
  
  
 
  
  
X 
  
Ophthalmoscopy  
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
 
  
  
  
 
  
  
X 
  
Record and assess adverse events  
Continuous 
  
Concomitant medications 
Continuous 
  
Confinement Period 
X 
Out7 
 
 
 
 
 
 
 
 
 
 
  
  
  
Drug administration 
X 
  
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Telephone call 
 
  
  
  
  
  
  
   
  
  
  
  
  
  
  
 
  
  
  
  
 
  
  
X 
 
EOS = End of Study Assessments; VAS = Visual Analog Scale; TFBUT = Tear film break-up time; OSDI = Ocular Surface Disease Index; WOCBP = women of childbearing potential 
 
1 Physical Examination includes head-eye-ears-nose-throat, cardiovascular, respiratory, gastrointestinal, dermatologic, and neurologic examinations.  
2 Blood pressure, heart rate, respiratory rate, oral temperature.  
3 Questionnaires will be completed prior to lab or PK timepoints. Ophthalmic assessments will follow lab or PK timepoints. 
4VAS assessment completed on Day 4 & 7 at 0h, 0.5h, 1h, 2h, 4h, 8h, 12h timepoints. VAS on Days 5 & 6 at 0, 4, 8, and 12 h 
5 Day 4 only 
6 30 minutes before staining tests 
7 Check-out after completion of all Day 8 assessments and 0 h dosing 
 


















CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 28 of 75 
Status: Final v3.0; Date 12Dec2019 
4. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• Safety and tolerability 
of SJP-0132 
• The number and severity of AEs including abnormal 
changes in clinical laboratory results, vital signs, and 
physical and ophthalmologic examinations  
• Pharmacokinetic (PK) 
profiles of SJP-0132  
• Part A: Cmax, tmax, tlast, AUC0-last, AUC0-∞, t1/2, AUC%extrap, 
AUMC0-last, AUMC0-∞, MRT0-last, MRT0-∞, Vd/F, CL/F, 
Cmax,norm, AUC0-last,norm, and AUC0-∞,norm 
• Part B: Cmax, tmax, tlast, AUC0-last, Cmax,norm, and AUC0-
last,norm on Day 1, Ctrough on Days 2, 4 and 8, and Rac 
• Efficacy of SJP-0132 
• Change from baseline (predose on Day 1) in eye dryness 
symptom (visual analog scale [VAS]) at 4 hours on Day 29 
• Change from baseline (predose on Day 1) in corneal 
fluorescein staining (CFS) score at the central zone on Day 
29 
Secondary 
• Efficacy of SJP-0132 
 
 
• Changes from baseline in dry eye signs: CFS scores at the 
central, superior, inferior, nasal, temporal and total zones, 
conjunctival lissamine green staining (CLGS) scores at 
each of 3 nasal and 3 temporal zone and total zone of 
bulbar conjunctiva, lid wiper epitheliopathy score, and tear 
film break-up time (TFBUT) at each time point tested 
• Changes from baseline in dry eye symptoms (VAS [ie, 
severity of eye dryness, discomfort, burning/stinging, 
sticky feeling, foreign body sensation, itching, pain, 
blurred vision, and sensitivity to light], ocular surface 
disease index [OSDI], Dry eye Questionnaire 5 [DEQ-5] 
scores) at each time point tested 
• Biomarker 
(Matrix 
Metalloproteinase-9 
(MMP-9), 
InflammaDry®) 
 










CONFIDENTIAL 
 
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Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
5. Have used or anticipates use of any prescription or over-the-counter medication, including 
topical medications such as ophthalmic solutions (except an ophthalmic solution specially 
provided by Sponsor, mydriatics, and stain used for trial examinations), nasal drops or 
spray, vitamins, alternative and complementary medicines (including herbal formulations) 
within 14 days or 5 half-lives (whichever is longer) before randomization or at any time 
during the study.  
6. Use or anticipates use of prescribed dry eye medications (e.g. Restasis and Xiidra) within 
28 days prior to randomization or at any time during the study. 
7. Have used or anticipates use CYP3A4 inducers, such as St. John’s Wort, within 14 days 
before randomization or at any time during the study. 
8. Have consumed red wine, grapefruit or grapefruit juice, Seville oranges, star fruit, or any 
products containing these items, or any foods that may inhibit CYP3A4, within 48 hours 
before randomization and throughout the duration of the study 
9. Have a positive urine alcohol test at Screening or Day –1   
10. Have a positive urine drug test at Screening or Day –1   
11. Has history of, or evidence of, alcohol or drug abuse within past 6 months prior to 
Screening  
12. Have a positive HBsAg, HCV antibody, or HIV test at Screening  
13. Have received another investigational medication within 90 days before randomization  
14. Contact lens wearers who cannot discontinue the wear over the trial period (i.e., from 
Screening to EOS)  
15. Have undergone eye surgery (including laser surgery) within the last 12 months or whom 
the Investigator considers unsuitable  
16. Subjects whom the Investigator considers are unable or unlikely to comply with the trial 
protocol or scheduled Screening or Admission (e.g., planned travel outside of the trial area 
for a substantial portion of the trial period, scheduled hospitalization during the trial period)  
17. Have a family history of sudden death  
18. Have cardiac disease (e.g., cardiac arrest, ischemic cardiac disease)  
19. Have abnormal serum electrolytes according to the judgment of the Investigator  
20. Have a BCVA worse than 20/100 in either eye. 
21. Current use of punctal plugs or anticipated insertion during study period. 
22. History of permanent punctal occlusion (cautery or laser). 
23. Any corneal abnormality or disease which might impact normal tear film spreading (eg: 
cornea scarring, keratoconus or pterygia). 
24. Active or history of significant corneal disease (recurrent erosions or herpetic keratitis). 
25. Known allergy or sensitivity to fluorescein, lissamine green or any of the study 
medications.  
 


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 34 of 75 
Status: Final v3.0; Date 12Dec2019 
6.3. 
Lifestyle Restrictions 
6.3.1. 
Meals and Dietary Restrictions 
1. Refrain from consumption of red wine, grapefruit or grapefruit juice, Seville oranges, star 
fruit, or any products containing these items, or any foods that may inhibit CYP3A4, 
within 48 hours before randomization and throughout the duration of the study. 
6.3.2. 
Caffeine, Alcohol, and Tobacco 
1. Subjects will abstain from ingesting caffeine- or xanthine-containing products (eg, coffee, 
tea, cola drinks, and chocolate) for 24 hours prior to the start of dosing on Day 1 of Part A 
and Days 1, 2, 4, and 8 of Part B, and for the remainder of the confinement period until 
after collection of the final pharmacokinetic (PK). Subjects will also abstain 24 hours prior 
to each weekly outpatient visit. 
2. Subjects will abstain from alcohol for 24 hours before the start of dosing on Day 1 of Part 
A and Days 1, 2, 4, and 8 of Part B until after collection of the final pharmacokinetic (PK).  
3. Use of tobacco products will not be allowed from screening until after the final follow-up 
visit. 
6.3.3. 
Activity 
1. Subjects will abstain from strenuous exercise for 24 hours before each blood collection for 
clinical laboratory tests. Subjects may participate in light recreational activities during 
studies (eg, watching television, reading). 
2. Subjects will be asked to refrain from the following for 24 hours prior to their visits: 
• Dangerous sport activities (eg, skiing, mountain climbing, etc.) 
• Swimming in a chlorinated pool 
• Challenging climates (eg, smoking rooms, sauna, etc.) 
6.4. 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently entered in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure subjects to meet the Consolidated Standards of Reporting 
Trials (CONSORT) publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened. 






CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 37 of 75 
Status: Final v3.0; Date 12Dec2019 
after breaking the mask. The date and reason that the mask was broken must be recorded in the 
source documentation and CRF, as applicable. 
7.7. 
Missed Doses 
If a dose is missed, the subject should dose as soon as they remember and adjust subsequent 
doses for that calendar day at 4-hour intervals, resuming protocol-indicated dosing on the next 
calendar day. Subject will record Date and time of actual dosing in the provided diary. 
7.8. 
Concomitant Therapy 
7.8.1. 
Recording Prior and Concomitant Medications 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or 
herbal supplements) that the subject is receiving at the time of enrollment or receives during the 
study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding concomitant or prior 
therapy. 
7.8.2. 
Prohibited Concomitant Medications, Treatments, and Procedures 
Subjects must abstain from taking prescription or nonprescription drugs (including topical 
medications such as ophthalmic solutions [except an ophthalmic solution specially provided by 
Sponsor, mydriatics, and stain used for trial examinations], nasal drops or spray, vitamins, 
alternative and complementary medicines [including herbal formulations] ) within 14 days or 5 
half-lives (whichever is longer) before randomization until completion of the follow-up visit, 
unless, in the opinion of the investigator and sponsor, the medication will not interfere with the 
study. Subjects must refrain from use of CYP3A4 inducers, such as St. John’s Wort, for 14 days 
before randomization or at any time during the study. Subjects must abstain from prescribed dry 
eye medications (e.g. Restasis and Xiidra) for 28 days before randomization or at any time during 
the study. 
7.8.3. 
Rescue Medicine 
No rescue medication will be provided. 
7.9. 
Treatment after the End of the Study 
Study medication will not be provided after the end of the study. 


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 38 of 75 
Status: Final v3.0; Date 12Dec2019 
8. 
Discontinuation/Withdrawal Criteria  
A subject may voluntarily discontinue participation in this study at any time.  It is important to 
document whether the withdrawal of consent is primarily due to an AE or other reason.  The 
Investigator may also, at his or her discretion, discontinue the subject from participating in this 
study at any time.  Withdrawn subjects will not be replaced. 
Subjects may be prematurely discontinued from the study for any of the following reasons: 
• Subject non-compliance 
• Investigator non-compliance 
• Subject requires concurrent prohibited medication during the course of the study.  If, in 
the opinion of the Investigator and the study medical monitor, such medication will not 
interfere with the conduct or interpretation of the study or compromise the safety of the 
subject, then the subject may continue to receive study medication.  If the subject is 
discontinued from study medication, they would remain in the study for safety 
assessments as needed.   
• Pregnancy of female subject 
• Discontinuation of the study at the request of the Sponsor, regulatory agency or an 
Institutional Review Board / Independent Ethics Committee 
• Grade 3 or 4 clinical AE considered causally related to treatment. 
If a subject meets a withdrawal criterion during treatment, procedures listed in the SoA for Part A 
check-out or Part B Day 29 EOS will be required. 
8.1. 
Discontinuation of Study Treatment  
If a clinically significant finding is identified after enrollment, the investigator or qualified 
designee will determine if the subject can continue in the study and if any change in subject 
management is needed. Any new clinically relevant finding should be reported as an AE. 
Procedures listed in the SoA for Part A check-out or Part B Day 29 EOS should be completed at 
the time of treatment discontinuation. 
8.2. 
Withdrawal from the Study 
• A subject may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. 
• If the subject withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
• If a subject withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 


CONFIDENTIAL 
 
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Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
• At the time of study discontinuation the End-of-Study procedures need to be completed. 
8.3. 
Lost to Follow Up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in the 
study. 
• Before a subject is deemed lost to follow up, the investigator or designee must make every 
effort to regain contact with the subject (where possible, 3 telephone calls and, if necessary, 
a certified letter to the subject’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the subject’s medical record. 
• Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up.  


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
Page 40 of 75 
Status: Final v3.0; Date 12Dec2019 
9. 
Study Assessments and Procedures 
• Study procedures and their timing are summarized in the SoA.  
• Protocol waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the sponsor immediately upon occurrence 
or awareness to determine if the subject should continue or discontinue study treatment. 
• Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
• Details for completion of each assessment will be included in the Study Manual. 
• All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria. The investigator will maintain a screening log to record details of 
all subjects screened and to confirm eligibility or record reasons for screening failure, as 
applicable.  
• Procedures conducted as part of the subject’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for screening or baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in the SoA. 
Table 9-1: Volume of Blood to be Collected from Each Subject 
Type of Sample 
Volume 
per 
Sample 
(mL) 
No. of Samples/ 
Subject 
Total Volume of Blood 
(mL)a 
Part A 
Part B 
Part A 
Part B 
Safety (including screening and 
post treatment assessments) 
 
 
 
 
 
- Hematology 
4.0 
3 
4 
12.0 
16.0 
- Serum chemistry 
8.5 
3 
4 
25.5 
34.0 
serology (HIV, HBsAg, 
HCV) 
8.5 
1 
1 
8.5 
8.5 
serum β-hCG pregnancy test 
(WOCBP only) 
4.9 
1 
2 
4.9 
9.8 
Pharmacokinetic samples 
2.0 
8 
9 
16.0 
18.0 
Loss by use of indwelling 
intravenous cannula 
1.0 
8 
9 
8.0 
9.0 
Total 
 
 
 
74.9 
95.3 
a 
Calculated as number of samples multiplied by amount of blood per sample. 
 
Note: An indwelling intravenous cannula may be used for blood sample collection. If a mandarin 
(obturator) is used, blood loss due to discard is not expected. 


CONFIDENTIAL 
 
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Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
• If blood samples are collected via an indwelling cannula, an appropriate amount 
(i.e., 1 mL) of fluid slightly greater than the dead space volume of the lock will be removed 
from the cannula and discarded before each blood sample is taken. After blood sample 
collection, the cannula will be flushed with saline and charged with a volume equal to the 
dead space volume of the lock. 
• The approximate amount of blood collected from subjects in Part A and Part B will be 75 
mL and 95 mL, respectively. Repeat or unscheduled samples may be taken for safety 
reasons or for technical issues with the samples. 
Daily Procedures – Part A 
Screening (Day -30 to Day -15) 
• Sign ICF 
• Record medical and medication history and demographic information (age, sex, race, iris 
color) 
• Review inclusion/exclusion criteria  
• Physical examination  
• Height (cm) and weight (kg) 
• Vital signs  
• DEQ-5 
• VAS 
• OSDI 
• Clinical laboratory tests (hematology, serum chemistry, urinalysis) 
• Serology (HIV, HBsAg, HCV) 
• Serum pregnancy test for WOCBP; FSH for post-menopausal women 
• Urine drug and alcohol screens 
• Visual acuity (Snellen) 
• Slit lamp biomicroscopy (w/out mydriatics) 
• MMP-9 (30 minutes before TFBUT and staining tests) 
• TFBUT 
• Corneal fluorescein staining (Baylor) 
• Lissamine green (Baylor + Lid Margin) 
• Aesthesiometer 
• Schirmer I without anesthesia 
• VAS with anesthesia 




CONFIDENTIAL 
 
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Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
• Vital signs  
• VAS 
• PK sampling 
• Slit lamp biomicroscopy (without mydriatics) 
• TFBUT 
• Corneal fluorescein staining (Baylor) 
• Lissamine green (Baylor + Lid Margin) 
• Intraocular Pressure (iCare tonometer) 
• Randomize to study treatment 
Day 1, 0 hour 
• Administer study drug 
Day 1, Postdose 
• Review AEs and concomitant medications 
• Physical examination at 1 hour 
• Vital signs at 0.5, 1, 2, 4, 8, and 12 hours 
• VAS at 0.5, 1, 2, 4, 8, and 12 hours 
• PK sampling at 0.25, 0.5, 1, 2, 4, 8, and 12 hours 
• Visual acuity at 12 hours 
• Slit lamp biomicroscopy (without mydriatics) at 1, 2, and 12 hours 
• TFBUT at 2 and 12 hours 
• Corneal fluorescein staining (Baylor) at 2 and 12 hours 
• Schirmer I without anesthesia at 12 hours 
• Intraocular Pressure (iCare tonometer) at 2 and 12 hours 
• Slit lamp biomicroscopy (w/ mydriatics; lens observation) at 12 hours 
• Ophthalmoscopy at 12 hours 
Day 2, 24 hours Postdose 
• Review AEs and concomitant medications 
• Physical Examination  
• Vital signs  
• VAS 


CONFIDENTIAL 
 
Senju Pharmaceutical Co., Ltd. 
Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
• Clinical laboratory tests (chemistry, hematology, urinalysis) 
• Visual Acuity (Snellen) 
• Slit lamp biomicroscopy (w/out mydriatics) 
• TFBUT 
• Corneal fluorescein staining (Baylor) 
• Schirmer I w/o anesthesia 
• Intraocular Pressure (iCare tonometer) 
• Slit lamp biomicroscopy (w/ mydriatics; lens observation) 
• Ophthalmoscopy 
• Check-out of clinic 
 
Part B 
Screening (Day -30 to Day -15) 
• Sign ICF 
• Record medical and medication history and demographic information 
• Review inclusion/exclusion criteria 
• Physical examination  
• Height (cm) and weight (kg) 
• Vital signs  
• DEQ-5 
• VAS 
• OSDI 
• Clinical laboratory tests (hematology, serum chemistry, urinalysis) 
• Serology (HIV, HBsAg, HCV) 
• Serum pregnancy test for WOCBP; FSH for post-menopausal women 
• Urine drug and alcohol screens 
• Visual acuity (Snellen) 
• Slit lamp biomicroscopy (w/out mydriatics) 
• MMP-9 (30 minutes before TFBUT and staining tests) 
• TFBUT 






CONFIDENTIAL 
 
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Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
• Ophthalmoscopy at 12 hours 
• Administer study drug at 4, 8, and 12 hours 
Days 2 and 3 
• Review AEs and concomitant medications 
• Physical examination at 0 hour  
• Vital signs at 0, 4, 8, and 12 hours 
• VAS at 0, 4, 8, and 12 hours 
• Visual acuity at 0 hours 
• PK sampling at predose on Day 2 (ie, Day 1, 24 hours) 
• Slit lamp biomicroscopy (without mydriatics) at 0 and 12 hours 
• TFBUT at 0 and 12 hours 
• Corneal fluorescein staining (Baylor) at 0 and 12 hours 
• Lissamine green (Baylor + Lid Margin) at 0 and 12 hours 
• Schirmer I without anesthesia at 0 hours on Day 2 
• Intraocular Pressure (iCare tonometer) at 0 hour 
• Administer study drug at 0, 4, 8, and 12 hours 
Days 4 through 7 
• Review AEs and concomitant medications 
• Physical examination at 0 hour 
• Vital signs at 0 hour 
• VAS on Day 4 and on Day 7 at 0, 0.5, 1, 2, 4, 8, and 12 hours; VAS on Days 5 and 6 at 0, 
4, 8, and 12 hours 
• PK sampling at 0 hour on Day 4 
• Visual acuity at 0 hours 
• Slit lamp biomicroscopy without mydriatics at 0 and 12 hours 
• TFBUT  at 0 and 12 hours 
• Corneal fluorescein staining (Baylor) at 0 and 12 hours 
• Lissamine green staining (Baylor +Lid Margin) at 0 and 12 hours 
• Administer study drug at 0, 4, 8, and 12 hours 
Day 8, Check Out 
• Review AEs and concomitant medications 


CONFIDENTIAL 
 
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Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
• Physical examination at 0 hour 
• Vital signs at 0 hour 
• VAS  at 0 hour 
• OSDI at 0 hour 
• PK sampling at 0 hour 
• Clinical laboratory tests (hematology, serum chemistry, urinalysis) at 0 hour 
• Visual Acuity (Snellen) at 0 hour 
• Slit lamp biomicroscopy without mydriatics at 0 hour 
• TFBUT  at 0 hour 
• Corneal fluorescein staining (Baylor) at 0 hour 
• Lissamine green staining (Baylor +Lid Margin) at 0 hour 
• Schirmer I without anesthesia at 0 hour 
• Intraocular pressure (iCare tonometer) at 0 hour 
• Slit lamp biomicroscopy w/ mydriatics (lens observation) at 0 hour 
• Ophthalmoscopy at 0 hour 
• Administer study drug at 0 hour 
• Dispense study drug for administration at home 
• Dispense diary and complete refresher education on completion of diary and self-
administration of study drug 
• Discharge subjects from clinic 
• Subjects self-administer study drug at 0, 4, 8, and 12 hours each day 
• Subjects record dosing times in diary 
Day 9 through Day 28 
• Subjects self-administer study drug at 0, 4, 8, and 12 hours each day 
• Subjects record dosing times in diary 
Day 15 ±2 and Day 22 ±2 
Subjects come to clinic for the following assessments (at 0 hour unless otherwise noted): 
• Review AEs and concomitant medications 
• Physical examination at 0 hour 
• Vital signs at 0 hour 
• VAS at 0, 4, and 8 hours 


CONFIDENTIAL 
 
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Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
• OSDI at 0 hour 
• Visual acuity at 0 hour 
• Slit lamp biomicroscopy w/out mydriatics at 0 hour 
• TFBUT at 0 hour 
• Corneal fluorescein staining (Baylor) at 0 hour 
• Lissamine green staining (Baylor +Lid Margin) at 0 hour 
• Intraocular Pressure (iCare tonometer) at 0 hour  
• Subjects self-administer study drug at 0, 4, 8, and 12 hours each day 
• Subjects record dosing times in diary 
• Dispense study drug for administration at home 
Day 29 ±2, EOS 
• Review AEs and concomitant medications 
• DEQ-5 at 0 hour 
• VAS  at 0, 4, and 8 hours 
• OSDI at 0 hour 
• MMP-9 at 0 hour (30 minutes before TFBUT and staining tests) 
• TFBUT  at 0 hour 
• Corneal fluorescein staining (Baylor) at 0 hour 
• Lissamine green staining (Baylor +Lid Margin) at 0 hour  
• Drug administration at 0 hour 
• Clinical laboratory tests (hematology, serum chemistry, urinalysis) at 2 hours 
• Serum pregnancy test for WOCBP only at 2 hours 
• Physical examination, including weight at 4 hours 
• Vital signs at 4 hours 
• Visual Acuity (Snellen) at 8 hours 
• Slit lamp biomicroscopy without mydriatics at 8 hour 
• Schirmer I without anesthesia at 8 hours 
• Intraocular pressure  (iCare tonometer) at 8 hours 
• Slit lamp biomicroscopy w/ mydriatics (lens observation) at 8 hours 
• Ophthalmoscopy at 8 hours 


CONFIDENTIAL 
 
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Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
Day 36 ±2 
• Follow-up telephone call to review AEs and concomitant medications 
 
9.1. 
Efficacy Assessments  
The following ocular assessments will be done during Part A at the time points listed: 
DEQ-5 
Screening, Day -1 
VAS 
Screening, Day -1, Day 1 (0 (predose), 0.5, 1, 2, 
4, 8, 12, 24 hours) 
OSDI© 
Screening, Day -1 
MMP-9 (InflammaDry) 
Screening, Day -1 
TFBUT 
Screening, Day 1 (0, 2, 12, 24 hours) 
Corneal fluorescein staining (Baylor) 
Screening, Day -1, Day 1 (0, 2, 12, 24 hours) 
Lissamine green staining (Baylor +Lid 
Margin [lid wiper epitheliopathy]) 
Screening, Day 1 (0 hour)  
 
The following ocular assessments will be done during Part B at the time points listed: 
DEQ-5 
Screening, Day -1, Day 29 
VAS 
Screening, Day -1, Day 1 (0, 0.5, 1, 2, 4, 8, 12 hours), Days 2 
and 3 (0, 4, 8, 12 hours), Days 4 and 7 (0, 0.5, 1, 2, 4, 8, 12 
hours), Days 5 and 6 (0, 4, 8, 12 hours) Day 8 (0 hour), Days 
15, 22 and 29 (0, 4, 8 hours) 
OSDI© 
Screening, Day -1, Days 8, 15, 22 and 29 at 0 hour 
MMP-9 (InflammaDry) 
Screening, Day -1, and 29 (0 hour) 
TFBUT 
Screening, Day 1 (0, 2 and 12 hours),  
Days 2 through 7 (0 and 12 hours) 
Days 8, 15, 22, and 29 (0 hour) 
Corneal fluorescein 
staining (Baylor) 
Screening, Day -1, Day 1 (0, 2 and 12 hours),  
Days 2 through 7 (0 and 12 hours) 
Days 8, 15, 22, and 29 (0 hour) 


CONFIDENTIAL 
 
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Protocol SJP-0132/1-01 
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Status: Final v3.0; Date 12Dec2019 
Lissamine green staining 
(Baylor +Lid Margin [lid 
wiper epitheliopathy]) 
Screening, Day 1 (0 and 12 hours),  
Days 2 through 7 (0 and 12 hours) 
Days 8, 15, 22, and 29 (0 hour) 
Please note: For Part A and B of this study all OSDI, DEQ-5 and VAS assessments will be 
completed prior to any laboratory or PK timepoints. TFBUT, Corneal fluorescein staining and 
Lissamine green staining will be scheduled to be completed following any laboratory or PK 
timepoints. 
9.2. 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA. 
9.2.1. 
Ocular Safety 
The following ocular safety assessments will be conducted during Part A at the time points listed: 
Visual acuity (Snellen) 
Screening, Day -1, Day 1 (12 and 24 hours) 
Slit lamp biomicroscopy 
(w/out mydriatics) 
Screening, Day 1 (0, 1, 2, 12, 24 hours)  
Aesthesiometer 
Screening 
Schirmer I 
Screening, Day -1, Day 1 (12 and 24 hours) 
VAS with anesthesia 
Screening 
Intraocular pressure 
(iCare tonometer) 
Screening, Day 1 (0, 2, 12, 24 hours) 
Slit lamp biomicroscopy  
(w/ mydriatics; lens observation) 
Screening, Day -1, Day 1(12 and 24 hours) 
Ophthalmoscopy 
Screening, Day -1, Day 1(12 and 24 hours) 
 
The following ocular safety assessments will be conducted during Part B at the time points listed: 
Visual acuity (Snellen) 
Screening, Day -1, Day 1 (12 hours),  
Days 2 through 8, 15, 22, and 29 (0 hour) 
Slit lamp biomicroscopy 
(w/out mydriatics) 
Screening, Day 1 (0, 1, 2, 12 hours), 
Days 2 through 7 (0 and 12 hours),  
Days 8, 15, 22, and 29 (0 hour)  
Aesthesiometer 
Screening 
Schirmer I 
Screening, Day -1, Day 1 (12 hours),  
Days 2, 8 and 29 (0 hour) 


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VAS with anesthesia  
Screening 
Intraocular pressure 
(iCare tonometer) 
Screening, Day 1 (0 and 12 hours),  
Days 2, 3, 8, 15, 22, and 29 (0 hour) 
Slit lamp biomicroscopy  
(w/ mydriatics; lens observation) 
Screening, Day -1, Day 1 (12 hours),  
Days 8 and 29 (0 hour) 
Ophthalmoscopy 
Screening, Day -1, Day 1 (12 hours),  
Days 8 and 29 (0 hour) 
Please note: For Part A and B of this study, all ocular safety assessments will be scheduled to be 
performed following laboratory and PK time points. 
9.2.2. 
Physical Examinations 
A complete physical examination will include, at a minimum, assessments of HEENT, the 
Cardiovascular, Respiratory, Gastrointestinal, Dermatologic, and Neurologic systems.  Height and 
weight will also be measured and recorded. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
9.2.3. 
Vital Signs 
Vital signs will be measured in a semi-supine position after 5 minutes rest and will include oral 
body temperature, systolic and diastolic blood pressure, heart rate, and respiratory rate. Vital signs 
will be measured before collection of blood samples for laboratory tests or PK. 


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9.2.4. 
Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical laboratory tests to be performed and to the SoA for the 
timing and frequency.  
The investigator must review the laboratory report, document this review, and record any clinically 
relevant changes occurring during the study in the AE section of the CRF. The laboratory reports 
must be filed with the source documents. Clinically significant abnormal laboratory findings are 
those which are not associated with the underlying disease, unless judged by the investigator to be 
more severe than expected for the subject's condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 
● If such values do not return to normal/baseline within a period of time judged reasonable 
by the investigator, the etiology should be identified and the sponsor notified. 
● All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA.  
● If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in subject management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.  
9.3. 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 4. 
AEs will be recorded from the beginning of the run-in phase. Any medical occurrence before run-
in will be recorded as medical history. AE will be reported by the subject (or, when appropriate, 
by a caregiver, surrogate, or the subject's legally authorized representative).  
The investigator and/or designees are responsible for detecting, documenting, and recording events 
that meet the definition of an AE or SAE and remain responsible for following up AEs that are 
serious, considered related to the study treatment or study procedures, or that caused the subject to 
discontinue the study (see Section 8).  
9.3.1. 
Time Period and Frequency for Collecting AE and SAE Information  
All SAEs will be collected from the beginning of the run-in phase to the follow-up visit. 
Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the Medical History/Current Medical Conditions section of the case 
report form (CRF) not the AE section. 
All SAEs will be recorded and reported to the sponsor or designee within 24 hours, as indicated in 
Appendix 4. The investigator will submit any updated SAE data to the sponsor within 24 hours of 
it being available. 


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Investigators are not obligated to actively seek AE or SAE in former study subjects. However, if 
the investigator learns of any SAE, including a death, at any time after a subject has been 
discharged from the study, and he/she considers the event to be reasonably related to the study 
treatment or study participation, the investigator must promptly notify the sponsor. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 4. 
9.3.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences.  
9.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs, will be followed until resolution, stabilization, the event is 
otherwise explained, or the subject is lost to follow-up (as defined in Section 8.3). Further 
information on follow-up procedures is given in Appendix 4. 
9.3.4. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a 
study treatment under clinical investigation are met.  
• The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, Institutional Review Boards (IRB)/Independent 
Ethics Committees (IEC), and investigators. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
• An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate according to local requirements. 
9.3.5. 
Pregnancy 
• Details of all pregnancies in female subjects and, if indicated, female partners of male 
subjects will be collected after the start of study treatment and until termination or 8 weeks 
after birth. 
• If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 5. 




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AUC%extrap 
percentage of AUC0-∞ that is due to extrapolation beyond tlast 
AUMC0-last 
area under the moment curve from time 0 to time of the last quantifiable 
concentration 
AUMC0-∞ 
area under the moment curve from time 0 to infinite time 
MRT0-last 
mean residence time from time 0 to time of the last quantifiable concentration 
MRT0-∞ 
mean residence time from time 0 to infinite time 
t1/2 
elimination half-life associated with the terminal slope (λz) of the 
semilogarithmic drug concentration-time curve, calculated as 0.693/λz 
Vd/F 
apparent volume of distribution 
CL/F 
apparent total body clearance 
Rac 
accumulation ratios calculated as (Ctrough on day 4) / (Ctrough on day 2) and (Ctrough 
on day 8) / (Ctrough on day 2) (Part B) 
9.6. 
Health Economics 
No Health Economic information will be collected. 
10. 
Statistical Considerations  
10.1. 
General Considerations  
The primary statistical analysis of the data will be descriptive in nature. For continuous variables 
this means calculation of the number of observations, mean, standard deviation, median, minimum, 
and maximum. Categorical variables will be summarized by subject counts and related 
percentages. For ordinal-scaled variables, a combination of the above may be employed as 
appropriate: frequency and percentage of observations within a category and means and standard 
deviations of the scores of the categories. For categorical and ordinal variables, percentages will 
be calculated based on non-missing data. 
10.2. 
Sample Size Determination  
No formal sample size and/or power calculations were performed for the study, however a sample 
size was chosen based on feasibility to allow total of 92 randomized subjects for Part A (n=32) 
and Part B (n=60). Approximately 32 subjects are expected to complete Part A and 60 subjects are 
expected to complete Part B. 


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10.3. 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
Population 
Description 
Enrolled  
Consist of all enrolled subjects. Subjects who signed the ICF. This 
population will be used in disposition outputs 
Safety set 
All subjects randomly assigned to study treatment and who take at 
least 1 dose of study treatment. Subjects will be analyzed 
according to the treatment they actually received. It will be the 
primary population for the safety and tolerability analysis.  
Full analysis set 
All subjects randomly assigned to study treatment and who take at 
least 1 dose of study treatment and have a post-baseline efficacy 
measurement. Subjects will be analyzed according to the treatment 
they actually received.  
Per protocol set 
All subjects who completes the study with at least 75% overall 
dosing compliance and without any other major protocol 
deviations/violations. 
Pharmacokinetic set 
All subjects who take at least 1 dose of active drug and have at 
least 1 quantifiable plasma concentration collected postdose 
without important protocol deviations/violations or events thought 
to significantly affect the PK. 
10.4. 
Statistical Analyses 
All the analysis will be carried out separately for Part A and Part B upon completion of the study 
visit (EOS). Data will be summarized by cohort and across all active dose levels. Complete 
details of the statistical analyses to be performed will be documented in a statistical analysis 
plan, which will be completed prior to database lock. This document will include more detail of 
analysis populations, summary strategies, and any amendments to the proposed analyses listed 
here, if necessary. Any changes to the statistical analysis plan will be outlined in the final study 
report.  


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10.4.1. 
Efficacy Analyses 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints. All analyses, summaries, and listings will be performed using SAS® software (Version 
9.4 or higher version) 
Endpoint 
Statistical Analysis Methods 
Primary 
Change from baseline (predose on Day 1) in eye dryness symptom 
(visual analog scale [VAS]) at 4 hours on Day 29 
Change from baseline (predose on Day 1) in corneal fluorescein 
staining (CFS) score at the central zone on Day 29 
Secondary 
Changes from baseline in dry eye signs: CFS scores at the central, 
superior, inferior, nasal, temporal and total zones, conjunctival 
lissamine green staining (CLGS) scores at each of 3 nasal and 3 
temporal zone and total zone of bulbar conjunctiva, lid wiper 
epitheliopathy score, and tear film break-up time (TFBUT) at each 
time point tested 
Changes from baseline in dry eye symptoms (VAS [ie, severity of eye 
dryness, discomfort, burning/stinging, sticky feeling, foreign body 
sensation, itching, pain, blurred vision, and sensitivity to light], ocular 
surface disease index [OSDI©], Dry eye Questionnaire 5 [DEQ-5] 
scores) at each time point tested 
Biomarker (Matrix Metalloproteinase-9 (MMP-9), InflammaDry®) 
The study eye will be the eye with the greater central zone corneal fluorescein staining score at 
predose on Day 1. If both eyes meet all of the inclusion and none of the exclusion criteria and the 
central zone corneal fluorescein staining scores are equal, the right eye (OD) will be designated as 
the study eye for the duration of this study.  
The fellow eye (non-study eye) will be treated with the product as per the assigned dosing 
schedule. 
Change in eye assessments will be summarized using descriptive statistics (mean, standard 
deviation, coefficient of variation (%CV), median, minimum, and maximum).  
For this study co-primary endpoints will be as follows: the differences between SJP-0132 and 
placebo in changes from baseline in eye dryness symptom (visual analog scale [VAS]) and change 
from baseline (predose on Day 1) in corneal fluorescein staining (CFS) score at the central zone 
on Day 29.  
Secondary endpoints are changes from baseline in dry eye signs: CFS scores at the superior, 
inferior, nasal, temporal and total zones, conjunctival lissamine green staining (CLGS) scores at 
each of 3 nasal and 3 temporal zone and total zone of bulbar conjunctiva, lid wiper epitheliopathy 
score, and tear film break-up time (TFBUT) at each time point tested. Changes from baseline in 
dry eye symptoms (VAS [ie, severity of eye dryness, discomfort, burning/stinging, sticky feeling, 
foreign body sensation, itching, pain, blurred vision, and sensitivity to light], ocular surface disease 


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index [OSDI©], Dry eye Questionnaire 5 [DEQ-5] scores) at each time point tested and Biomarker 
(Matrix Metalloproteinase-9 (MMP-9), InflammaDry®). 
10.4.2. 
Safety Analyses 
All safety analyses will be performed on the Safety Population.  
Endpoint 
Statistical Analysis Methods 
Primary 
The number and severity of AEs including abnormal changes from baseline in 
clinical laboratory results, vital signs, and physical and ophthalmologic 
examinations 
Safety assessments and changes from baseline in vital signs, clinical laboratory results, adverse 
events (AEs), treatment-emergent AEs (TEAEs), will be summarized using descriptive statistics 
as outlined in the statistical analysis plan including but not limited to (mean, standard deviation, 
coefficient of variation (%CV), median, minimum, and maximum). Concomitant medications and 
physical examination findings will be listed.  
10.4.3. 
Pharmacokinetic Analyses  
Plasma samples will be analyzed to determine the concentration of SJP-0132. Pharmacokinetic 
variables will be calculated using non-compartmental analysis.  
Individual PK concentrations and PK parameters will be listed. The PK data will be summarized 
descriptively by dose/cohort using appropriate statistics (eg, N, n, arithmetic mean, SD, minimum, 
median, maximum, geometric mean [PK parameters only, as appropriate], and coefficient of 
variance [CV%]). Graphical presentations will include by-subject and mean concentrations plots 
which will be presented on linear and semi-logarithmic scales. Scatterplots of individual and 
geometric mean exposure parameters [AUC0-∞, AUC0-last, and Cmax] will be presented by dose. 
Additional graphical presentations of PK data may be added at the discretion of the PK scientist  
Part A: Cmax, tmax, tlast, AUC0-last, AUC0-∞, AUC%extrap, t1/2, AUMC0-last, AUMC0-∞, MRT0-last, MRT0-
∞, Vd/F, CL/F, Cmax,norm, AUC0-last,norm, AUC0-∞,norm.  
Part B: Part B: Cmax, tmax, tlast, AUC0-last, Cmax,norm, and AUC0-last,norm on Day 1, Ctrough on Days 2, 4 
and 8, and Rac. 








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Appendix 2: Clinical Laboratory Tests  
The tests detailed below will be performed by the local laboratory.  
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
Protocol-Required Safety Laboratory Assessments 
Laboratory Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC 
Count 
with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical Chemistry 
BUN 
Potassium 
Creatinine 
Sodium 
Glucose (fasting) 
Calcium  
Total Protein 
Aspartate Aminotransferase (AST)/ 
Serum Glutamic-Oxaloacetic 
Transaminase (SGOT) 
Alanine Aminotransferase (ALT)/ 
Serum Glutamic-Pyruvic Transaminase 
(SGPT) 
Alkaline phosphatase 
Total and direct bilirubin  
Routine Urinalysis 
• Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, 
nitrite, leukocyte esterase by dipstick 
• Microscopic examination (if blood or protein is abnormal) 
Other Screening Tests 
• Follicle-stimulating hormone and estradiol (as needed in 
women of non-childbearing potential only) 
• Urine drug screen (to include at minimum: amphetamines, 
barbiturates, 
cocaine, 
opiates, 
cannabinoids 
and 
benzodiazepines)] 
• Alcohol urine test 
• Serum human chorionic gonadotropin (hCG) pregnancy test 
(as needed for women of childbearing potential) at Screening 
and Day 29 (Part B). Urine pregnancy test at Day -1. 
• Serology (HIV antibody, hepatitis B surface antigen 
[HBsAg], and hepatitis C virus antibody)  
Investigators must document their review of each laboratory safety report. 


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Appendix 3: Study Governance Considerations 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
• The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated.  
• Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study subjects.  
• The investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established 
by the IRB/IEC 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the subject 
or his/her legally authorized representative and answer all questions regarding the study.  
• Subjects must be informed that their participation is voluntary. Subjects will be required to 
sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center.  
• The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 


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• Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study.  
• A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative.  
Data Protection 
• Subjects will be assigned a unique identifier by the sponsor. Any subject records or datasets 
that are transferred to the sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred.  
• The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject.  
• The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor before 
submission. This allows the sponsor to protect proprietary information and to provide 
comments.  
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In 
this case, a coordinating investigator will be designated by mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
Dissemination of Clinical Study Data 
This study and its results will be posted on the US National Institutes of Health’s website 
www.ClinTrials.gov. 
Data Quality Assurance 
• All subject data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator 
is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.  
• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.  
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.  


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• Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of subjects are being protected; and that the 
study is being conducted in accordance with the currently approved protocol and any other 
study agreements, ICH GCP, and all applicable regulatory requirements.  
• Records and documents, including signed ICFs, pertaining to the conduct of this study must 
be retained by the investigator for 2 years after study completion unless local regulations 
or institutional policies require a longer retention period (ie, 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). No 
records may be destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without written 
notification to the sponsor.  
Source Documents 
• Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available. 
 
Study and Site Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies have 
been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are not 
limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of subjects by the investigator 
• Discontinuation of further study treatment development 


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Appendix 4: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or clinical study subject, temporally 
associated with the use of study treatment, whether or not considered related to the study 
treatment. 
• 
A treatment-emergent adverse event (TEAE) is any AE that occurs or worsens in either 
intensity or frequency after exposure to study drug in the treatment phase. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study treatment. 
 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (eg, electrocardiogram, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the investigator (ie, not related to progression of underlying 
disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even though it 
may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment 
or a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it 
is an intentional overdose taken with possible suicidal/self-harming intent. Such overdoses 
should be reported regardless of sequelae. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AE or SAE if they fulfil the definition of an AE or SAE.  
 


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Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the subject’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the subject 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the subject has been detained (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that would 
not have been appropriate in the physician’s office or outpatient setting. Complications that 
occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. 


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• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other outcomes 
listed in the above definition. These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization, or development of drug dependency or drug abuse. 
Recording and AE and/or SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF (eg, event 
term, date and time of onset, date and time of resolution, anatomical site or system). If the 
AE/SAE is to an eye, the study eye or fellow eye must be identified. 
• 
It is not acceptable for the investigator to send photocopies of the subject’s medical records 
to Senju in lieu of completion of the AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by 
Senju. In this case, all subject identifiers, with the exception of the subject number, will be 
redacted on the copies of the medical records before submission to Senju. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to 1 of the following categories:  
• 
Grade 1 (Mild): asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 


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• 
Grade 2 (Moderate): minimal, local or non-invasive intervention indicated; limiting age 
appropriate instrumental ADL*. 
• 
Grade 3 (Severe): medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL. 
• 
Grade 4 (Life threatening): urgent intervention indicated 
• 
Grade 5 (Death): death related to AE 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
* Activities of daily living 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study treatment and each 
occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study treatment administration 
will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Senju. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Senju. 
• 
The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 


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Follow-up of AEs and SAEs 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Senju to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may include 
additional laboratory tests or investigations, histopathological examinations, or consultation 
with other health care professionals. 
• 
Drug related AEs or SAEs will be followed up until resolution, stabilization, or the event is 
otherwise explained, or the subject is lost to follow-up. 
• 
Non-drug-related AEs or SAEs will not be followed after the telephone follow-up call is 
complete. Any non-drug-related AEs or SAEs, that have not been resolved, stabilized, or 
otherwise explained by the follow-up telephone visit will be referred to the subjects Primary 
Care Physician for ongoing care. 
• 
If a subject dies during participation in the study or during a recognized follow-up period, 
the investigator will provide Senju with a copy of any post-mortem findings including 
histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The investigator will submit any updated SAE data to Senju within 24 hours of receipt of 
the information. 
 
Reporting of SAEs 
SAE Reporting to Senju via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to Senju will be the electronic data collection 
tool. 
• 
If the electronic system is unavailable for more than 24 hours, then the site will use the 
paper SAE data collection tool (see next section). 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study subject or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, 
then the site can report this information on a paper SAE form (see next section) or to the 
Senju by telephone. 
• 
Contacts for SAE reporting can be found in the Study Reference Manual. 
 


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SAE Reporting to Senju via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to Senju. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
• 
Contacts for SAE reporting can be found in the Study Reference manual 
 
 


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Appendix 5: Contraceptive Guidance and Collection of Pregnancy Information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s: review of the subject’s medical 
records, medical examination, or medical history interview. 
 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 12 
months of amenorrhea, a single FSH measurement is insufficient.  
• Females on HRT and whose menopausal status is in doubt will be required to use one 
of the non-hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
 
Contraception Guidance 
Male subjects 
• Male subjects with female partners of childbearing potential are eligible to participate if 
they agree to ONE of the following [during the protocol-defined time frame in Section 
6.1]:  
Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a 
long term and persistent basis) and agree to remain abstinent 
• Agree to use a male condom plus partner use of a contraceptive method with a failure rate 
of <1% per year as described below when having penile-vaginal intercourse with a woman 
of childbearing potential who is not currently pregnant 


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Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal 
intercourse or use a male condom during each episode of penile penetration [during the protocol-
defined time frame]  
Female subjects 
Female subjects of childbearing potential are eligible to participate if they agree to use a highly 
effective method of contraception consistently and correctly as described below. 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a  
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation 
• Oral  
• Intravaginal  
• Transdermal  
Progestogen only hormonal contraception associated with inhibition of ovulation 
• Oral  
• Injectable  
Highly Effective Methods That Are User Independent  
• Implantable progestogen only hormonal contraception associated with inhibition of 
ovulationIntrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
Bilateral tubal occlusion 
Vasectomized partner  
A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.  
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the subject.  
NOTES:  
a) Typical use failure rates may differ from those when used consistently and correctly. Use 
should be consistent with local regulations regarding the use of contraceptive methods for 
subjects participating in clinical studies.  
b) Hormonal contraception may be susceptible to interaction with the study treatment, which 
may reduce the efficacy of the contraceptive method. In this case, two highly effective methods 
of contraception should be utilized during the treatment period and for at least 30 days after 
the last dose of study treatment  


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Pregnancy Testing 
WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive pregnancy test. 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when pregnancy is 
otherwise suspected  
 
Collection of Pregnancy Information  
Male subjects with partners who become pregnant  
• 
The investigator will attempt to collect pregnancy information on any male subject’s female 
partner who becomes pregnant while the male subject is in this study. This applies only to 
male subjects who receive SJP-0132. 
• 
After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within 24 hours of learning of the partner’s pregnancy. The female 
partner will also be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to the sponsor. Generally, the follow-up will 
be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of fetal status (presence or absence of anomalies) or 
indication for the procedure.  
Female Subjects who become pregnant  
• 
The investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the sponsor within 24 hours of learning of a subject's pregnancy. The 
subject will be followed to determine the outcome of the pregnancy. The investigator will 
collect follow-up information on the subject and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date. Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion 
is always considered to be an SAE and will be reported as such. Any post-study pregnancy-
related SAE considered reasonably related to the study treatment by the investigator will be 
reported to the sponsor as described in Section 9.3. While the investigator is not obligated to 
actively seek this information in former study subjects, he or she may learn of an SAE through 
spontaneous reporting.  
• 
Any female subject who becomes pregnant while participating in the study will be withdrawn 
from the study.