A Randomized, Double-blind, Placebo Parallel-controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of TJ0113 Capsule in Patients With Early-stage Parkinson's Disease
Phase: PHASE2
Conditions: Parkinson Disease
Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 11, 2025
Confidential
Clinical Trial Protocol
A randomized, double-blind, placebo parallel-controlled
Phase II clinical trial to evaluate the efficacy and safety of
TJ0113 capsule in patients with early-stage Parkinson's
disease
Protocol No.:
TJJS01-201
Version No.:
4.0
Version Date:
February 17, 2025
Sponsor:
Hangzhou PhecdaMed Co., Ltd.
Confidentiality Statement
All information contained within this study protocol is the property of the
sponsor and is therefore only for review by the investigators, co-
investigators, Ethics Committee, regulatory authorities and other relevant
institutions. Without the written approval of the sponsor, it is strictly
forbidden to disclose any information to personnel unrelated to the study,
except for necessary explanations made for signing the informed consent
form with participants who may participate in the study.

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Protocol Signature Page-Sponsor
I agree:
•
To strictly follow the protocol, Good Clinical Practice (GCP) and applicable
regulations and laws when carrying out the study.
•
To keep all materials provided by Hangzhou PhecdaMed Co., Ltd. according to the
confidentiality requirements. It must be indicated that these materials are confidential
when they are required to be submitted to the Institutional Review Board (IRB) or
Independent Ethics Committee (IEC).
I have read the full text of the protocol and agree to all the contents.
Yasu Zhang
Responsible Person of the
Sponsor
Signature
Date

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Protocol Signature Page-Contract Research Organization
I agree:
•
To strictly follow the protocol, Good Clinical Practice (GCP) and applicable
regulations and laws when carrying out the study.
•
To keep all materials provided by Hangzhou PhecdaMed Co., Ltd. according to
the confidentiality requirements. It must be indicated that these materials are
confidential when they are required to be submitted to the Institutional Review
Board (IRB) or Independent Ethics Committee (IEC).
I have read the full text of the protocol and agree to all the contents.
Zhipei Wei
Project Manager
Signature
Date

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Protocol Signature Page-Statistical Analysis Institution
I agree:
•
To strictly follow the protocol, Good Clinical Practice (GCP) and applicable
regulations and laws when carrying out the study.
•
To keep all materials provided by Hangzhou PhecdaMed Co., Ltd. according to the
confidentiality requirements. It must be indicated that these materials are confidential
when they are required to be submitted to the Institutional Review Board (IRB) or
Independent Ethics Committee (IEC).
I have read the full text of the protocol and agree to all the contents.
Qing Li
Statistician
Signature
Date

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Protocol Signature Page-Study Site
I agree:
•
To strictly follow the protocol, Good Clinical Practice (GCP) and applicable
regulations and laws when carrying out the study.
•
To keep all materials provided by Hangzhou PhecdaMed Co., Ltd. according to the
confidentiality requirements. It must be indicated that these materials are confidential
when they are required to be submitted to the Institutional Review Board (IRB) or
Independent Ethics Committee (IEC).
I have read the full text of the protocol and agree to all the contents.
Principal Investigator
Signature
Date

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Clinical Study Management Institution or Participating Parties
Principal Investigator
Site Name
The Second Affiliated Hospital Zhejiang University School of Medicine
Principal
Investigator
Wei Luo
Title
Deputy
Director
of
Department of Neurology
and Director of Ward
Contact Address
No.
88
Jiefang
Road,
Shangcheng District, Hangzhou,
Zhejiang
Postal
Code
310009
Tel.
13757120109
E-mail
luoweirock@zju.edu.cn
Sponsor
Company
Name
Hangzhou PhecdaMed Co., Ltd.
Project Leader
Yasu Zhang
Title
Clinical Operations Director
Contact
Address
Room 301, Building 2, No. 2626
Yuhangtang Road, Cangqian Street,
Yuhang
District,
Hangzhou,
Zhejiang
Postal
Code
311121
Tel.
18658149612
E-mail
yasu.zhang@phecdamed.co
m
Contract Research Organization
Company
Name
Hangzhou TigerMed Consulting Co., Ltd.
Project
Leader
Zhipei Wei
Title
Project Manager
Contact
Address
18/F,
Block
A,
Shengda
Science Park, No. 19, Jugong
Road,
Binjiang
District,
Hangzhou
Postal
Code
310051
Tel.
15810535207
E-mail
zhipei.wei@tigermedgrp.com
Data Management
Company
Name
Hangzhou TigerMed Consulting Co., Ltd.
Project
Leader
Yan Li
Title
Data
Management
Project
Leader
Contact
Address
18/F, Block A, Shengda Science
Park,
No.
19,
Jugong
Road,
Binjiang District, Hangzhou
Postal
Code
310051
Tel.
13472877395
E-mail
yoyo.li@tigermedgrp.com
Statistical Analysis Institution (Statistical Analysis of Efficacy and Safety)
Company
Name
Hangzhou TigerMed Consulting Co., Ltd.

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Project
Leader
Qing Li
Title
Manager of Statistics Department
Contact
Address
18/F,
Block
A,
Shengda
Science
Park,
No.
19,
Jugong
Road,
Binjiang
District, Hangzhou
Postal
Code
310051
Tel.
13277058167
E-mail
green.li@tigermedgrp.com

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Table of Contents
Protocol Signature Page-Sponsor........................................................................................... 1
Protocol Signature Page-Contract Research Organization..................................................2
Protocol Signature Page-Statistical Analysis Institution...................................................... 3
Protocol Signature Page-Study Site........................................................................................4
Clinical Study Management Institution or Participating Parties........................................5
Table of Contents......................................................................................................................7
List of Abbreviations and Definitions of Terms................................................................... 11
1 Protocol Summary...............................................................................................................15
1.1 Synopsis......................................................................................................................15
1.2 Schedule of Activities (SoA)......................................................................................27
2 Background Information....................................................................................................33
2.1 Disease Introduction...................................................................................................33
2.2 Introduction to TJ0113 Capsules................................................................................34
2.3 Summary of Non-clinical Studies.............................................................................. 34
2.3.1 Non-clinical Pharmacology.............................................................................35
2.3.2 Non-clinical Pharmacokinetics........................................................................37
2.3.3 Toxicology.......................................................................................................42
2.4 Summary of Clinical Trials of TJ0113 Capsules........................................................45
2.4.1 Trial Design..................................................................................................... 45
2.4.2 Trial Results.....................................................................................................46
2.5 Benefit/Potential Risk Assessment.............................................................................49
2.5.1 Risk Assessment..............................................................................................49
2.5.2 Benefit Assessment..........................................................................................49
2.5.3 Benefit/Risk Assessment................................................................................. 50
3 Trial Objectives and Endpoints..........................................................................................51
3.1 Trial Objectives.......................................................................................................... 51
3.2 Trial Endpoints........................................................................................................... 51
4 Selection and Withdrawal of Subjects...............................................................................54
4.1 Inclusion Criteria........................................................................................................54
4.2 Exclusion Criteria.......................................................................................................54
4.3 Definition and Handling of Screen Failures...............................................................57
4.4 Criteria for Early Withdrawal from the Trial..............................................................57
4.5 Criteria for Study Termination/Site Closure...............................................................59
5 Overall Trial Design............................................................................................................ 60
5.1 Trial Design................................................................................................................ 60
5.1.1 Overall Design.................................................................................................60
5.1.2 Trial Period......................................................................................................60
5.2 Justification for Design (Population, Dose, etc.)........................................................61
5.2.1 Justification for Overall Study Design............................................................ 61
5.2.2 Justification for Dose.......................................................................................61
5.3 Randomization and Blinding......................................................................................62

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Confidential
5.3.1 Randomization.................................................................................................62
5.3.2 Blinding...........................................................................................................63
5.4 Definition of End-of-Study (EOS)............................................................................. 64
5.5 Definition and Handling of Loss to Follow-up.......................................................... 64
6 Study Treatment.................................................................................................................. 65
6.1 Investigational Products............................................................................................. 65
6.2 Drug Storage...............................................................................................................65
6.3 Drug Dispensing.........................................................................................................65
6.4 Drug Receipt, Record and Accountability..................................................................66
6.5 Drug Return and Destruction..................................................................................... 66
7 Treatment for Study Participants...................................................................................... 67
7.1 Study Treatment......................................................................................................... 67
7.2 Concomitant Medication............................................................................................ 67
7.2.1 Permitted Concomitant Medications/Therapies.............................................. 67
7.2.2 Prohibited Concomitant Medications/Therapies.............................................67
7.3 Compliance of Study Subjects................................................................................... 68
8 Endpoint-Related Assessment............................................................................................ 69
8.1 Efficacy Assessment...................................................................................................69
8.1.1 MDS-UPDRS.................................................................................................. 69
8.2 Safety Assessment...................................................................................................... 70
8.2.1 Vital Signs....................................................................................................... 70
8.2.2 Physical Examination......................................................................................70
8.2.3 12-lead ECG....................................................................................................70
8.2.4 Laboratory Tests.............................................................................................. 71
8.3 Evaluation of Exploratory Indicators......................................................................... 72
8.3.1 Exploratory Inflammatory Indicators..............................................................72
8.3.2 Exploratory PD Biomarkers............................................................................ 73
8.3.3 Exploratory Skeletal Muscle Mass and Function Assessment........................ 73
8.3.4 Exploratory Genomic Resequencing...............................................................73
8.4 Tests/Assessments Required for V1 during Screening Period Only.......................... 73
8.5 Parameters to be Tested Under a Fasted State............................................................74
8.6 Sample Submission Plan............................................................................................ 74
8.7 Trial Procedure........................................................................................................... 74
8.7.1 Screening Period..............................................................................................75
8.7.2 Treatment Period............................................................................................. 79
8.7.3 Follow-up Period (Telephone Follow-up; V7, D91, W13)............................. 82
8.7.4 Early Withdrawal Visit.................................................................................... 82
8.7.5 Unscheduled Visit............................................................................................84
9 AE-related Assessment........................................................................................................85
9.1 Definition of AEs........................................................................................................85
9.1.1 AEs.................................................................................................................. 85
9.1.2 Treatment-Emergent Adverse Events (TEAEs)...............................................85
9.1.3 Treatment-Related Adverse Events (TRAEs)..................................................85

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9.1.4 Serious Adverse Events (SAEs)...................................................................... 85
9.1.5 Adverse Drug Reactions (ADRs).................................................................... 86
9.1.6 Suspected Unexpected Serious Adverse Reactions (SUSARs).......................86
9.2 Causal Relationship....................................................................................................87
9.3 Determination of the Severity.................................................................................... 89
9.4 Collection, Recording and Reporting of AEs.............................................................90
9.4.1 Collection and Recording of AEs and SAEs...................................................90
9.4.2 Reporting of SAEs...........................................................................................94
9.4.3 Reporting of SUSARs..................................................................................... 94
9.5 Reporting of Special Conditions................................................................................ 95
9.5.1 Death............................................................................................................... 95
9.5.2 Pregnancy........................................................................................................ 96
9.5.3 AEs Related to Overdose or Medication Error................................................96
10 Data Management............................................................................................................. 98
10.1 Completion and Transfer of Source Data and Case Report Form............................98
10.2 Design and Establishment of Database.................................................................... 98
10.3 Data Entry and Modification....................................................................................98
10.4 Data Review............................................................................................................. 99
10.5 Data Coding..............................................................................................................99
10.6 Data Lock................................................................................................................. 99
11 Statistical Analyses.......................................................................................................... 101
11.1 Sample Size............................................................................................................ 101
11.2 Statistical Analysis Population............................................................................... 101
11.3 General Analysis.....................................................................................................101
11.4 Statistical Analysis Methods...................................................................................102
11.4.1 Demographics and Baseline........................................................................ 102
11.4.2 Analysis for Primary Endpoint.................................................................... 102
11.4.3 Sensitivity Analysis..................................................................................... 103
11.4.4 Analysis for Secondary Endpoints...............................................................103
11.4.5 Analysis for exploratory endpoint............................................................... 103
11.4.6 Sub-group Analysis..................................................................................... 104
12 Trial Management........................................................................................................... 105
12.1 Statement................................................................................................................105
12.2 Ethical Considerations............................................................................................105
12.3 Source Data Verification.........................................................................................106
12.4 Quality Assurance/Audit........................................................................................ 106
12.5 Informed Consent...................................................................................................107
12.6 Trial Protocol Revision Rules.................................................................................108
12.7 Protocol Deviations................................................................................................ 108
12.8 Case Report Form...................................................................................................109
12.9 Monitoring..............................................................................................................109
12.10 Intellectual Property..............................................................................................111
12.11 Subject's Privacy...................................................................................................111

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13 Paper Publications...........................................................................................................113
14 Clinical Data Archiving...................................................................................................114
14.1 Source Data and Source Documents...................................................................... 114
14.2 Data Archiving of Study Site..................................................................................114
14.2.1 Materials related to the Ethics Committee.................................................. 114
14.2.2 Materials related to Trial Conduct...............................................................114
14.3 Data Archiving of Sponsor..................................................................................... 115
15 Protocol Amendments..................................................................................................... 116
16 References.........................................................................................................................117
17 Appendices........................................................................................................................119
17.1 Appendix I: Definition of Women of Childbearing Potential and Contraceptive
Requirements for Subjects......................................................................................................119
17.2 Appendix II: Calculation of Ccr............................................................................. 120

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List of Abbreviations and Definitions of Terms
Abbreviations/Terms
Full Name
ADR
Adverse Drug Reactions
AE
Adverse Event
AFP
Alpha-fetoprotein
ALT
Alanine Aminotransferase
ASMI
Appendicular Skeletal Muscle Mass Index
AST
Aspartate Aminotransferase
AUC0-inf
Area Under the Plasma Concentration-Time Curve from Time Zero
to Infinity
AUC0-inf,ss
Area Under the Plasma Concentration-Time Curve from Time Zero
to Infinity at Steady State
AUC0-last
Area Under the Plasma Concentration-Time Curve from Time Zero
to Time of Last Quantifiable Concentration
AUC0-t
Area Under the Plasma Concentration-Time Curve from Time Zero
to Time T
AUC0-t,ss
Area Under the Plasma Concentration-Time Curve from Time Zero
to Time T at Steady State
AUC0-24h
Area Under the Plasma Concentration-Time Curve from Time 0 to
24 h Post-Dose
BID
Twice Daily
BMI
Body Mass Index
CA125
Carbohydrate Antigen 125
CA153
Carbohydrate Antigen 153
CA199
Carbohydrate Antigen 199
CCCP
Carbonylcyanide-3-Chlorophenylhydrazone
Ccr
Creatinine Clearance
CEA
Carcinoembryonic Antigen
Cmax
Maximum Concentration
Cmax,ss
Maximum Steady-State Concentration
COX
Cyclo-Oxygenase
CRO
Contract Research Organization
CTCAE
Common Terminology Criteria for Adverse Events
CYP
Cytochrome P450
DA
Dopamine
DXA
Dual-energy X-ray Absorptiometry

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
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Confidential
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
FAS
Full Analysis Set
FE
Food Effect
F-PSA
Free Prostate Specific Antigen
GCP
Good Clinical Practice
GFAP
Glial Fibrillary Acidic Protein
GPCR
G-Protein-Coupled Receptor
HBsAg
Hepatitis B Surface Antigen
HCV
Hepatitis C Virus
HED
Human Equivalent Dose
HIV
Human Immunodeficiency Virus
ICF
Informed Consent Form
ICH
International Conference on Harmonization of Technical
Requirements for Registration of Pharmaceuticals for Human Use
IC50
Half-Maximal Inhibitory Concentration
IEC
Independent Ethics Committee
IFN
Interferon
IL
Interleukin
INR
International Normalized Ratio
IRB
Institutional Review Board
IWRS
Interactive Web Response System
MAD
Multiple Ascending Dose
Max
Maximum
Mcl-1
Myeloid Cell Leukemia 1
MDS-UPDRS
Unified Parkinson's Disease Rating Scale
MedDRA
Medical Dictionary for Regulatory Activities
Median
Median
MI
Myocardial Infarct
Min
Minimum
MMRM
Mixed-Effects Model for Repeated Measures
MPTP
1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine
mRNA
Messenger Ribonucleic Acid

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
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Version 4.0/date: February 17, 2025
Confidential
MTD
Maximum Tolerated Dose
mtDNA
Mitochondrial Deoxyribonucleic Acid
NCI
National Cancer Institute
NMPA
National Medical Products Administration
NOAEL
No Observed Adverse Effect Level
NYHA
New York Heart Association
OAT1
Organic Anion Transporter 1
PCR
Polymerase Chain Reaction
PD
Parkinson's Disease
P-gp
P-Glycoprotein
PK
Pharmacokinetics
PPS
Per-Protocol Set
PT
Preferred Term
QA
Quality Assurance
QD
Once Daily
Q1
First Quartile
Q3
Third Quartile
Rac(AUC)
Ratio of Accumulation of the Area Under the Plasma Drug
Concentration-Time Curve at Steady State
Rac(Cmax)
Ratio of Accumulation of Maximum Concentration at Steady State
ROS
Reactive Oxygen Species
SAD
Single Ascending Dose
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SCC
Squamous Cell Carcinoma Antigen
SD
Standard Deviation
SDV
Source Data Verification
SN
Substantia Nigra
SoA
Schedule of Activities
SS
Safety Set
Str
Striatum
SUSAR
Suspected Unexpected Serious Adverse Reaction
TBIL
Total Bilirubin
TEAE
Treatment-Emergent Adverse Event

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Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Tmax
Time to Maximum Concentration
TNF
Tumor Necrosis Factor
T-PSA
Total Prostate Specific Antigen
TRAE
Treatment-Related Adverse Events
t1/2
Half-Life
t1/2,ss
Half-Life at Steady State
ULN
Upper Limit of Normal
URAT1
Urate Transporter 1
Vss
Steady-State Volume of Distribution
WHO DD
World Health Organization Drug Dictionary
6-OHDA
6-Hydroxydopamine

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
1 Protocol Summary
1.1 Synopsis
Protocol No.
TJJS01-201
Trial Title
A Randomized, Double-blind, Placebo Parallel-Controlled Phase II Clinical
Trial to Evaluate the Efficacy and Safety of TJ0113 Capsule in Patients with
Early-stage Parkinson's Disease
Version No.
4.0
Version Date
February 17, 2025
Sponsor
Hangzhou PhecdaMed Co., Ltd.
Phase
Phase II
Indication
Parkinson's disease (PD)
Trial Objectives
Primary Objectives

To assess the efficacy of TJ0113 capsules in the treatment of patients
with early-stage PD.
Secondary Objectives

To assess the efficacy of TJ0113 capsules in the treatment of patients
with early-stage PD;

To assess the safety of TJ0113 capsules in the treatment of patients
with early-stage PD.
Exploratory Objectives

To explore the changes in inflammatory indicators in early-stage PD
patients treated with TJ0113 capsules;

To explore the effect of TJ0113 capsules on PD biomarkers in early-
stage PD patients;

To explore the effect of TJ0113 capsules on skeletal muscle mass and
function in early-stage PD patients;

To explore the association between the efficacy of TJ0113 capsules
and the genomic characteristics in early-stage PD patients.
Trial Endpoints
Primary Endpoints

Changes from baseline in scores of the Unified Parkinson's Disease

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
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Confidential
Rating Scale (MDS-UPDRS) Part III (motor examination) in subjects
after 12 weeks of treatment. Evaluation time point: ≥12 hours from
the most recent dose of anti-PD drug.
Secondary Endpoints

Efficacy Endpoints

Changes from baseline in scores of MDS-UPDRS Part III (motor
examination) in subjects after 1, 4, 8 weeks of treatment. Evaluation
time point at each visit: ≥12 hours from the most recent dose of anti-
PD drug;

Changes from baseline in scores of MDS-UPDRS Part III (motor
examination) in subjects after 1, 4, 8, 12 weeks of treatment.
Evaluation time point at each visit: 2 ± 1 hours from the most recent
dose of anti-PD drug;

Changes from baseline in scores of MDS-UPDRS Part I, II and
IV in subjects after 1, 4, 8 and 12 weeks of treatment;

Changes from baseline in the total scores of MDS-UPDRS in subjects
after 1, 4, 8, 12 weeks of treatment, including:
-
Total score 1: II+III; wherein, the evaluation time point for
MDS-UPDRS Part III (motor examination) is ≥12 hours from
the most recent dose of anti-PD drug;
-
Total score 2: II+III; wherein, the evaluation time point for
MDS-UPDRS Part III (motor examination) is 2 ± 1 hours from
the most recent dose of anti-PD drug;
-
Total score 3: I+II+III; wherein, the evaluation time point for
MDS-UPDRS Part III (motor examination) is ≥12 hours from
the most recent dose of anti-PD drug;
-
Total score 4: I+II+III; wherein, the evaluation time point for
MDS-UPDRS Part III (motor examination) is 2 ± 1 hours from
the most recent dose of anti-PD drug;
-
Total score 5: I+II+III+IV; wherein, the evaluation time point for
MDS-UPDRS Part III (motor examination) is ≥12 hours from
the most recent dose of anti-PD drug;
-
Total score 6: I+II+III+IV; wherein, the evaluation time point for
MDS-UPDRS Part III (motor examination) is 2 ± 1 hours from
the most recent dose of anti-PD drug.

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
Safety Endpoints

Adverse events (AEs);

Laboratory test;

Vital signs;

Physical examination;

12-lead electrocardiogram (ECG).

Exploratory Endpoint

Changes from baseline in inflammatory indicators after 4, 8, 12
weeks of treatment;

Changes from baseline in α-synuclein and glial fibrillary acidic
protein (GFAP) after 12 weeks of treatment;

Changes from baseline in appendicular skeletal muscle mass index
(ASMI) measured by dual-energy X-ray absorptiometry (DXA) after
12 weeks of treatment;

Changes from baseline in muscle strength (grip strength) after 12
weeks of treatment;

Changes from baseline in 6-meter walking speed test after 12 weeks
of treatment;

The association between the efficacy of TJ0113 capsules and the
genomic characteristics in early-stage PD patients.
Trial Design and
Methodology
This study is a randomized, double-blind, placebo parallel-controlled phase II
clinical trial which is designed to assess the efficacy and safety of TJ0113
capsules in the treatment of patients with early-stage PD. It is planned to include
approximately 150 subjects with early-stage PD who will be randomized in a
1:1 ratio into two cohorts (Cohort 1: 200 mg dose group; Cohort 2: 400 mg dose
group). Within each cohort, subjects who have been successfully screened will
be randomly assigned to TJ0113 capsules group and the placebo group in a ratio
of 2:1 within each stratum based on a stratification factor whether they have
been receiving levodopa, the background medication for PD (yes vs. no) at a
stable dose. Among them, approximately 50 subjects will receive TJ0113
capsules and approximately 25 subjects will receive the placebo. In this study,
there will be approximately 50 subjects in each of the TJ0113 capsules 200 mg
group, TJ0113 capsules 400 mg group and the placebo group.
After randomization, subjects will receive the oral administration of TJ0113
capsules or the placebo for 12 consecutive weeks and continue to receive
follow-up visits for 1 week (telephone follow-up) after the end of treatment. For
subjects who have been receiving the anti-PD drug at a stable dose for at least 4
weeks prior to study entry, the original regimen of the background medication
for PD should be maintained during the study.
Screening period (up to 4 weeks)

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At screening, the subject will be assigned a “screening number” for ID
identification after signing the informed consent form. The day of first dose for
subjects screened successfully is taken as Day 1 (D1) of the trial (for other days,
by this rule); and subjects are screened within 28 to 2 days before the start of the
trial, and the required eligible subjects are screened. The scale scores,
demographic data, medical history, medication history, physical examinations,
height and weight, vital signs and laboratory tests of the subjects before the trial
are recorded.
Treatment period (12 weeks)
Subjects who have been successfully screened will receive oral administration of
the drugs as required on D1, once daily for 12 weeks.
Follow-up period (1 week, telephone follow-up)
Follow-up will be continued for 1 week after the end of the treatment period,
and AE and concomitant medication information will be collected via telephone
follow-up. If an AE/SAE occurs during the study, it will be followed up by the
investigator until it has been clinically recovered, stabilized, returns to the
screening or baseline level (if baseline level is known), the subject is lost to
follow-up (e.g., no more information is available or the subject/caregiver refuses
to provide any information), or dead.
Total Number of
Subjects
There are about 150 subjects, with approximately 50 subjects in each of the
TJ0113 capsules 200 mg group, TJ0113 capsules 400 mg group and the placebo
group.
Number of Study Sites
Approximately 7 sites
Study Duration
The duration of this study is expected to be approximately 6 months.
Each subject will participate in the study for up to approximately 17 weeks,
including a screening period of up to 4 weeks, a treatment period of 12 weeks,
and a follow-up period of 1 week.
Subject Selection
Criteria
Inclusion Criteria:
Subjects who meet all of the following criteria will be eligible for this study:
1.
Subjects who voluntarily participate in the clinical trial, and have signed
the informed consent form (ICF), are able to understand and follow the
study protocol, willing to visit the study site on time, fully understand the
content, process and potential adverse reactions of the study, and indicate
the date of signing the ICF;
2.
Males or females aged 30-80 years (both inclusive) at the time of signing
the ICF;
3.
Subjects who are diagnosed with PD according to the Diagnostic Criteria
for Parkinson's Disease in China (2016 edition);
4.
The scores of modified Hoehn and Yahr Scale at screening are 1-2.5 (both
inclusive);

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
5.
Subjects who have not previously received anti-PD drugs; or those who
have previously used any anti-PD drugs but have not received such drug
within 4 weeks before study entry; or those who have received the anti-PD
drug at a stable dose for at least 4 weeks before study entry and agree to
maintain the original treatment regimen during the study;
6.
Subjects with the scores of MDS-UPDRS Part III of ≥22 at screening (it
should be scored ≥12 hours apart from the most recent dose of the anti-PD
drug for subjects who have been receiving an anti-PD drug at a stable dose
for at least 4 weeks prior to study entry);
7.
Subjects of childbearing potential (including spouses of male subjects) who
have no childbearing or sperm donation plan from the end of the screening
period to within 6 months after the last dose and are willing to use at least
one effective method (see Appendix I for details) for contraception.
Exclusion Criteria:
Subjects who meet any of the following criteria will be excluded from this
study:
1.
Presence of any medical condition that may interfere with full participation
in the study, including but not limited to the following: medical history of
epilepsy or any complications, medical history of hemolytic anemia,
pulmonary embolism, respiratory depression, active psychiatric disease, or
malignancy; positive tumor marker detection results at screening and
judged by the investigator to be clinically significant;
2.
Subjects who have experienced a New York Heart Association (NYHA)
Class III or above congestive heart failure, unstable angina pectoris, acute
myocardial infarction, hemorrhagic stroke (stroke), and ischemic stroke
(including transient ischemic attack) within 6 months before screening; or
those who have undergone any percutaneous coronary intervention or
coronary artery bypass grafting, heart valve repair/replacement; or those
with severe arrhythmia as judged by the investigator at the time of
screening;
3.
Subjects with prior personal or family history of long-QT syndrome, family
history of sudden death of any immediate family members (meaning a
parent, child, or sibling) prior to the age of 40 years; and/or personal
history of unexplained syncope within 1 year prior to screening; and/or
QTcF > 450 ms (male), QTcF > 470 ms (female) measured by ECG at rest
during screening;
4.
Subjects with unstably controlled hypertension at screening, defined as the

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
systolic blood pressure ≥160 mmHg and/or the diastolic blood pressure ≥
100 mmHg (verify before randomization);
5.
Subjects with symptomatic orthostatic hypotension at screening, or who
experiences a decrease in systolic blood pressure of ≥30 mmHg or a
decrease in diastolic blood pressure of ≥15 mmHg within 3 minutes when
changing from the supine to the standing position (verify before
randomization);
6.
Atypical PD (e.g., Parkinsonism, multiple system atrophy, progressive
supranuclear palsy), or secondary PD (e.g., delayed or drug-induced PD);
7.
Subjects who have clinically significant hepatic insufficiency which is
defined as the total bilirubin (TBIL) > 2 × upper limit of normal (ULN) or
alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >
2 × ULN;
8.
Subjects who have clinically significant renal insufficiency (creatinine
clearance [Ccr] < 30 mL/min, see the calculation formula in Appendix II;
9.
Any condition (e.g., severe arthritis, severe dyskinesia, traumatic injury
with permanent physical disability) that may affect the MDS-UPDRS
motor examination;
10.
Subjects who have a history of suicidal intention (including actual
attempts, interrupted attempts, or failed attempts) and are at risk of
committing suicide as judged by the investigator;
11.
Subjects who suffer from severe mental abnormalities (anxiety, depression)
as judged by the investigator, and the depression or anxiety score as rated
by the Part I of the MDS-UPDRS is ≥3 at screening;
12.
Subjects who have taken any serotonin reuptake inhibitors (such as
fluoxetine, paroxetine, trazodone, citalopram, escitalopram, etc.) within 4
weeks prior to screening;
13.
Subjects who have dementia or moderate or above cognitive dysfunction
and the MDS-UPDRS score for 1.1 cognitive impairment is ≥3 at
screening;
14.
Subjects who have a history of surgical treatment for PD (e.g., deep brain
stimulation, pallidotomy, etc.), or those who have undergone any major or
medium surgery or have experienced any serious trauma or serious
infection within 3 months prior to screening, those who are unsuitable for
this study at the discretion of the investigator or plan to undergo any
surgical treatment (excluding an outpatient surgery that has no impact on

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
subject safety or study results as judged by the investigator) during the
study;
15.
Subjects who have participated in a clinical trial that involves the
administration of an investigational drug (a new chemical entity), device,
or surgery within 3 months or 5 half-lives before screening, whichever is
longer;
16.
Subjects with evidence of alcoholism (≥14 units of alcohol per week on
average, 1 unit ≈360 mL of beer, 45 mL of liquor, or 150 mL of wine) or
drug abuse within 6 months prior to screening that may interfere with the
subject's understanding of the study or completion of the study as judged
by the investigator;
17.
Subjects who are known to have hypersensitivity/allergic reaction or
intolerance to any component of the investigational product;
18.
Subjects with a history of hepatitis B, or positive for any of the hepatitis B
surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human
immunodeficiency
virus
(HIV)
antibody,
and
Treponema
pallidum
antibody (TP-Ab) at screening;
19.
Pregnant or breastfeeding women;
20.
Subjects who are unable to swallow oral drugs, or have any condition that
may significantly affect the absorption, distribution, metabolism and
excretion of the drug, or any condition that may pose a hazard to subjects
participating in the study, as judged by the investigator;
21.
Subjects who have a history of organ transplantation (excluding corneal
transplantation);
22.
Subjects who have donated or lost blood of ≥400 mL, or received blood
transfusions within 3 months prior to screening;
23.
Subjects who have any other conditions that may affect study compliance
as deemed by the investigator, or those who are unable to participate in the
study for their own reasons.
Concomitant
Medications/Therapies
Permitted Concomitant Medications/Therapies
Concomitant medications/therapies allowed to be administered from signing of
the ICF to 1 week after the last dose of the investigational product include:

Background medications for PD that have been stably used before
study entry, of which the treatment regimen can remain unchanged
(for subjects who have used any background medications for PD
including levodopa, if any AE such as dyskinesia occur, the dose of

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
levodopa is
allowed
to be
reduced at
the
discretion of
the
investigator).

Other concomitant medication or therapies that have already been
used at the time of screening, of which the original drug/therapy type,
dose or treatment frequency and setting should remain unchanged as
much as possible.

Drugs required to be used for treating the AEs.
Prohibited Concomitant Medications/Therapies
The following medications/therapies are prohibited during the period from
signing the ICF until 1 week after the last dose of the investigational product:

Any procedure/surgery that may affect the progression of PD,
including but not limited to brain surgery (such as stereotactic
destruction and deep brain stimulation) or traditional Chinese
medicine physiotherapy (such as acupuncture), etc.;

Any drugs other than investigational product that may affect the
progression of PD (excluding those which have been on a stable dose
for PD at the time of study entry);

Serotonin
reuptake
inhibitors
(such
as
fluoxetine,
paroxetine,
trazodone, citalopram, escitalopram, etc.);

Any unauthorized drugs (i.e., other investigational drugs that are
currently tested in clinical trials and have not been approved for
marketing).
The investigator will determine and record the use of any emergency
medication, drug name, dose, route of administration, purpose of treatment, start
and end date of administration.
If subjects have used any prohibited drug or non-drug therapy, it will be
recorded as a protocol deviation. The investigator will decide whether to
continue the follow-up or withdraw the subjects from the study based on the
severity of the deviation and the subjects’ condition.
Early Withdrawal
from the Trial
Criteria for Early Withdrawal from the Trial:
Subjects may voluntarily request for study withdrawal at any time, or may be
withdrawn from the study at any time at the request of the investigator or the
sponsor for safety, behavioral or administrative reasons.
Withdrawal at the subject's discretion
If the subjects are unwilling to continue the clinical trial, they have the right to
withdraw their consent and withdraw from the study at any stage.
Withdrawal at the investigator's discretion
It refers to the condition during the study in which the investigator finds that an

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
enrolled subject is no longer suitable for the participation in the study and
decides that the subject should be withdrawn from the study. These conditions
include, but are not limited to:

Continuing the study may affect the safety of the subject and be
unfavorable to the subject at the discretion of the investigator based
on the following clinical considerations:
-
QTcF >500 ms at rest (after resting for at least 5 minutes; the
average of two measurements taken within 20 minutes) or an
increase of >60 ms from baseline;
-
Discontinuation of study treatment due to hepatic event or
hepatic function abnormal:

ALT or AST>8×ULN; or

ALT or AST>5×ULN for over 2 weeks; or

ALT or AST>3×ULN and (TBIL>2×ULN or International
Normalized Ratio [INR]>1.5); or

ALT or AST>3×ULN, with fatigue, nausea, vomiting, right
upper quadrant pain or tenderness, pyrexia, rash, or
eosinophilia (> 5%).
-
Occurrence of other intolerable AEs which requires treatment
discontinuation as judged by the investigator;

Any major protocol deviations (such as subjects who fail to meet the
inclusion criteria have been mistakenly included in the study) or
protocol violations, which may have a significant impact on the
evaluation of the efficacy and safety of the drug;

Subjects have poor compliance that affects efficacy and safety
assessment;

Female subjects are pregnant;

Subjects are lost to follow-up;

Subjects have participated in other clinical trials (which is defined as
having signed the ICF of any other study) during the study;

Subjects have been unblinded due to various reasons;

Other circumstances in which the subject needs to be withdrawn from
the trial at the discretion of the investigator.
Handling of Subjects Early Withdrawn
Subjects who have early withdrawn from the study should complete the early
withdrawal visit (if it is less than 7 days from the date of the previous visit,

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
repeated tests of the same item can be waived) within 7 days after the
investigator's awareness, unless they voluntarily decide to withdraw from the
study and refuse to have early withdrawal visit.
For subjects who withdraw from the study due to an AE or SAE, the investigator
should take appropriate treatment measures according to the actual situation of
the subjects, and closely follow up their condition until the AE or SAE is
clinically recovered, stabilized, returns to screening or baseline level (if baseline
level is known), the subject is lost to follow-up (e.g., no more information is
available or the subject/caregiver refuses to provide any information), or dead,
which will be recorded in the original data.
For all the subjects who have early withdrawn from the study, their study
medical records should be retained and recorded in the electronic case report
form (eCRF), and the EOT page and the reason for failure in completing the
study should be filled out.
Investigational
Products
In this study, the investigational products include the investigational drug
(TJ0113 capsules) and the placebo.
TJ0113 Capsules
Placebo
Active
Ingredient
TJ0113
None
Dosage Form
Capsules
Capsules
Strength
100 mg
100 mg
Package Size
30 capsules/bottle
30 capsules/bottle
Description
Opaque rich yellow hard
capsules, and with pale
pink solid contents
Opaque rich yellow hard
capsules, and with off-white
solid contents
Storage
Conditions
Protected from light, keep
in tight container at 2℃-
8℃
Protected from light, keep in
tight container at 2℃- 8℃
Provided by
Hangzhou PhecdaMed Co., Ltd.
Method of
Administration
Take orally on an empty stomach in the morning, once
daily, and fast within half an hour after the administration.
It can be taken together with the background medication
for PD. It is recommended that subjects should take the
drug at the same time ± 1 h each day as much as possible.
Statistical Analyses
Estimation of Sample Size:
The sample size of this study is not determined based on the formal statistical
assumptions and it is expected to include approximately 150 subjects with early-
stage PD, who will be randomized in a 1:1 ratio into two cohorts (Cohort 1: 200
mg dose group; Cohort 2: 400 mg dose group). Within each cohort, the subjects
will be randomized into the TJ0113 capsules group and the placebo group in a
ratio of 2:1, with approximately 50 subjects receiving TJ0113 capsules and
approximately 25 subjects receiving the placebo. In this study, there will be
approximately 50 subjects in each of the TJ0113 capsules 200 mg group, TJ0113
capsules 400 mg group and the placebo group.

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
General Analysis
Statistical analyses of efficacy and safety will be performed using the SAS
software (V9.4 or later).
Unless otherwise specified, descriptive statistics for continuous variables
included the number of subjects (n), mean, standard deviation (SD), median,
first quartile (Q1), third quartile (Q3), minimum (Min), and maximum (Max).
Categorical variables will be summarized using descriptive statistics including
number of subjects (n) and the percentage (%).
Unless otherwise specified, it will be summarized by the TJ0113 capsules 200
mg group, TJ0113 capsules 400 mg group, and the placebo group.
Analysis sets
Full analysis set (FAS): including all randomized subjects who have received at
least one dose of investigational product.
Per-protocol set (PPS): including subjects in the FAS who have not experienced
major protocol deviations that affect the primary efficacy endpoint.
Safety set (SS): including all subjects who have received at least one dose of the
investigational product and have undergone at least one post-dose safety
assessment.
Demographics and baseline characteristics will be analyzed based on FAS, the
efficacy analyses will be performed based on both FAS and PPS, and the safety
analyses will be performed based on SS.
Demographics and Baseline
Demographic and baseline characteristics will be summarized using descriptive
statistics. Baseline is defined as the last valid measurement or assessment (if
applicable) before the first dose of the study drug.
Analysis for Primary Endpoint
The primary objective of this study is to assess the efficacy of TJ0113 capsules
in the treatment of patients with early-stage PD. The main concern of interest is
the treatment difference in terms of the changes from baseline in the MDS-
UPDRS Part III (motor examination) scores after 12 weeks of treatment between
the TJ0113 capsules group and the placebo group.
Definition of estimand:

Population: patients with early-stage PD

Endpoint: changes from baseline in scores of MDS-UPDRS Part III
(motor examination) after 12 weeks of treatment. Evaluation time point:
≥12 hours from the most recent dose of anti-PD drug.

Treatment: treatments will be randomly assigned; subject will be
randomized in a 1:1 ratio to two cohorts (200 mg dose group and 400
mg dose group); and within each cohort, the subjects will be
randomized in a 2:1 ratio to the TJ0113 capsules group and the placebo
group.

Concomitant event and management strategy: For any concomitant

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
medication (excluding the investigational product and stable anti-PD
medications at the time of enrollment) or treatment that could
potentially impact the PD disease process, a therapeutic strategy will be
employed.

Population-level summary: differences in the least square mean of the
changes from baseline in MDS-UPDRS Part III (motor examination)
scores after 12 weeks of treatment between the TJ0113 capsules group
and the placebo group.
The analysis will be performed using a mixed models for repeated measures
(MMRM) with the changes from baseline in the MDS-UPDRS Part III scores
after 12 weeks of treatment as the dependent variable, whether subjects have
been receiving levodopa, the background medication for PD (yes vs. no) at a
stable dose at baseline and the baseline MDS-UPDRS Part III score as the
covariates, and the treatment group, visit, and the treatment group-by-visit
interaction as the fixed effects.
Sensitivity Analysis
The sensitivity analysis of the primary endpoint will be performed using the
analysis of covariance. The model will use the changes from baseline in the
MDS-UPDRS Part III scores after 12 weeks of treatment as the dependent
variable, whether subjects have been receiving levodopa, the background
medication for PD (yes vs. no) at a stable dose at baseline, the baseline MDS-
UPDRS Part III score, and the treatment group as the covariates.
After the primary endpoint is imputed by using different mechanisms for
imputing the missing data, the sensitivity analysis will be performed using the
same method as that for the primary analysis. The detailed statistical methods
will be separately described in the statistical analysis plan (SAP).
Analysis for secondary endpoints

Efficacy analysis: the secondary efficacy endpoints will be summarized
using the same statistical methods described above for primary
endpoint.

Safety analysis: includes AEs and other safety-related parameters,
which will be summarized by the descriptive statistics.
Detailed statistical methods will be described in a separate SAP.
Analysis for Exploratory Endpoint
Exploratory endpoint (inflammatory indicators, α-synuclein, GFAP, ASMI, grip
strength, 6-meter walking speed) will be analyzed using the analysis of variance
or nonparametric tests, and the correlations between the parameters will be
analyzed using the Spearman's or Pearson's correlation coefficients. Detailed
statistical methods will be described in a separate SAP.

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
1.2 Schedule of Activities (SoA)
Study Flow Chart
Study Process
Screening
period
Treatment period
Follow-up
Period
(Telephon
e)
Early
Withdrawal
Visit20
Visit No.
V1
V2
V3
V4
V5
V6
V7
-
Visit duration (W)
W-4~-1
W-1
W1
W4
W8
W12
W13
-
Visit duration (D)
D-28~-2
D-1
D7
D28
D56
D84
D91
-
Window period
(days)
-
-
±1
±2
±2
±2
±3
-
Signing of the ICF
X
Fasting at visit1
X
X
X
X
X
X
X
Review of inclusion
and exclusion criteria
X
X
Randomization
X
Demographics2
X
History of diagnosis
and treatment of PD
X
Other medical history
and treatment history3
X
Other personal
history4
X
Vital signs5
X
X
X
X
X
X
X
Physical examination6
X
X
X
X
X
X
X
12-lead ECG7
X
Xa
X
X
X
X
X
Hematology8
X
Xa
X
X
X
X
X
Blood chemistry9
X
Xa
X
X
X
X
X
Urinalysis10
X
Xa
X
X
X
X
X
Weight measurement
and Ccr calculation11
X
Xa
X
X
X
Coagulation
function12
X
Xa
X
X
X
X
X
Screening for
infectious diseases13
X
B-ultrasound14
X
Tumor marker
detection15
X
Serum pregnancy test
(only for women of
childbearing
potential)
X
Urine pregnancy test
(only for women of
childbearing
potential)
X
X
X
X
X
X

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Study Process
Screening
period
Treatment period
Follow-up
Period
(Telephon
e)
Early
Withdrawal
Visit20
Visit No.
V1
V2
V3
V4
V5
V6
V7
-
Visit duration (W)
W-4~-1
W-1
W1
W4
W8
W12
W13
-
Visit duration (D)
D-28~-2
D-1
D7
D28
D56
D84
D91
-
Window period
(days)
-
-
±1
±2
±2
±2
±3
-
Test of serum follicle
stimulating hormone
(only for women with
menopause within 24
months or uncertain
menopausal status)
X
Collection of blood
samples for
exploratory analysis
(inflammatory
indicators) 16
X
X
X
X
X
Collection of blood
samples for
exploratory analysis
(α-synuclein and
GFAP)17
X
X
X
Collection of blood
samples for
exploratory analysis
(genomic
resequencing)
Xb
X
X
Exploratory skeletal
muscle mass and
function assessment
(ASMI, grip strength
and 6-meter walking
speed test)18
X
X
X
Assessment using
modified Hoehn and
Yahr Scale
X
MDS-UPDRS score19
X
X
X
X
X
X
X
Dispensing of
investigational
product
X
X
X
X
Return of
investigational
product
X
X
X
X
Administration
of
investigational
product
The first dose will be administered on
D1 and the last dose on D84. Take
orally on an empty stomach in the
morning, once daily. Fast for half an
hour after oral administration. At site
visits,
it
should
be
administered
together
with
the
background
medication for PD. It is recommended
that subjects should take the drug at
the same time ± 1 h each day as much
as possible.

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
Study Process
Screening
period
Treatment period
Follow-up
Period
(Telephon
e)
Early
Withdrawal
Visit20
Visit No.
V1
V2
V3
V4
V5
V6
V7
-
Visit duration (W)
W-4~-1
W-1
W1
W4
W8
W12
W13
-
Visit duration (D)
D-28~-2
D-1
D7
D28
D56
D84
D91
-
Window period
(days)
-
-
±1
±2
±2
±2
±3
-
Dispensing of diary
cards/instructions for
completion
X
X
X
X
Return of diary cards
X
X
X
X
X
Concomitant
Medication
X
X
X
X
X
X
X
X
AEs
X
X
X
X
X
X
X
X
Note:
a.
If hematology, blood chemistry, coagulation function test, urinalysis, 12-lead ECG examinations,
weight measurement and calculations of creatinine clearance (Ccr) have been performed within 7 days
(exclusive) before D-1, these tests are not required to be repeated on D-1; otherwise, they are required
to be re-tested on D-1 and the eligibility for the study entry should be confirmed according to the test
results.
b.
Collection of blood samples for exploratory analysis of genomic resequencing: each subject will be
collected once at V2 (if not collected at V2, it is allowed to be supplemented at V6 or early withdrawal
visit).
c.
If screen failure is caused due to abnormal results during the screening process, and if the investigator
judges that there is a clear justification for retesting, and the tests can be repeated within the time
window once, but the reason for repeating the test should be recorded. Subjects with screening failure
are only allowed for re-screening once during the enrollment stage of this study. Additional
medications are not allowed to correct the abnormal values (e.g., hepatoprotective drugs used to
address hepatic function abnormal) prior to the re-screening. Parameters that are allowed for retesting
include: blood pressure, ECG, creatinine, aspartate aminotransferase (AST), alanine aminotransferase
(ALT), and total bilirubin (TBIL).
d.
Follow-up period (V7) collects AE and concomitant medication information through telephone follow-
up.
1.
Subjects must be fasted before each visit (fast for at least 10 hours overnight without depriving of
water). It is recommended that fasting blood samples be collected between 7:00 a.m. and 10:00 a.m.,
and the specific collection time point is subject to the implementation of each study site. The
investigational product or background medication for PD should not be administered prior to blood
collection. If the subject has not fasted before the visit, an additional fasting collection should be
scheduled.
Parameters to be tested under fasted conditions include: hematology, blood chemistry, B-ultrasound,
and exploratory inflammatory indicators. There is no fasting requirement for other parameters.

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
2.
Demographics: date of birth, age, gender, ethnicity, height, weight, body mass index (BIM), etc.;
3.
Other medical history and treatment history: including other past and current medical history
(excluding PD), treatment history, surgical history and surgical plan, etc.
4.
Other personal history: including but not limited to family history, allergy history, alcohol
consumption history, substance abuse history, blood transfusion history, and childbearing plan, etc.
5.
Vital signs: including respiration, pulse, body temperature, and blood pressure. Among them, blood
pressure measurement on the day of V1 and before randomization at V2 should be measured after the
subject has rested in a supine position for at least 5 min. After the supine blood pressure measurement
is completed, let the patient stand upright and complete the measurement of standing blood pressure
within 3 min in a standing resting state; for other vital signs measurements, it can be measured with
the subject in a sitting position after having rested for at least 5 min.
6.
Physical examination: including skin and mucous membranes, lymph nodes, head, neck, chest,
abdomen, spine and limbs, nervous system and mental state.
7.
12-lead ECG: it should be performed with the subject in a supine position after having rested for at
least 5 min. Two measurements will be taken within 20 minutes, and the average value is calculated
and rounded to the nearest integer. The parameters include: heart rate, PR interval, QRS complex
duration, uncorrected QT interval, and Fridericia-corrected QTc (QTcF).
8.
Hematology: white blood cell count, absolute neutrophil count, neutrophil percentage, absolute
lymphocyte count, lymphocyte percentage, absolute monocyte count, monocyte percentage, absolute
eosinophil count, eosinophil percentage, absolute basophil count, basophil percentage, red blood cell
count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin content,
mean corpuscular hemoglobin concentration, red blood cell distribution width, platelet count, mean
platelet volume, platelet hematocrit, and platelet distribution width.
9.
Blood chemistry: fasting blood glucose, bile acid, total protein, albumin, globulin, albumin/globulin
ratio, total bilirubin (TBIL), direct bilirubin, indirect bilirubin, alanine aminotransferase (ALT),
aspartate
aminotransferase
(AST),
gamma-glutamyltransferase,
alkaline
phosphatase,
lactate
dehydrogenase, creatine kinase, creatine kinase isoenzyme MB, urea/blood urea nitrogen, blood uric
acid,
creatinine,
potassium,
sodium,
chloride,
calcium,
magnesium,
inorganic
phosphorus,
triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein
cholesterol.
10.
Urinalysis: urine glucose, urine bilirubin, urine ketone body, urine pH, urine protein, urobilinogen,
urine nitrite, urinary occult blood, urine white blood cells, urine red blood cells, urinary sediment
microscopic examination (red blood cells, white blood cells) and urine specific gravity.
11.
Ccr is calculated based on weight measurement results and creatinine levels in blood chemistry tests,
and the calculation formula is shown in Appendix II. If weight has been measured when collecting
demographics at V1, it is not necessary to repeat the weight measurement during that visit.
12.
Coagulation function test: including prothrombin time, activated partial thromboplastin time,

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thrombin time, international normalized ratio and fibrinogen.
13.
Screening for infectious diseases: including hepatitis B five-item test (hepatitis B surface antigen
[HBsAg], hepatitis B surface antibody, hepatitis B e antigen, hepatitis B e antibody, hepatitis B core
antibody), hepatitis C virus (HCV) antibody test, human immunodeficiency virus (HIV) antibody test
and treponema pallidum antibody test.
14.
B-ultrasound: detection sites include liver, gallbladder, pancreas, spleen, and kidney.
15.
Tumor marker detection: including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA),
carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125) (only for females), total
prostate specific antigen (T-PSA) (only for males), free prostate specific antigen (F-PSA) (only for
males), carbohydrate antigen 153 (CA153), squamous cell carcinoma antigen (SCC), ferritin.
16.
Inflammatory indicators in the exploratory analysis include interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6,
IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α; the
specific test indicators are subject to the actual implementation of each center.
17.
Blood samples for exploratory analysis of α-synuclein and glial fibrillary acidic protein (GFAP)
indicators need to be sent to the central laboratory for testing after collection. All other test samples in
this trial will be tested in local laboratories.
18.
Exploratory skeletal muscle mass and function assessment: including appendicular skeletal muscle
mass index (ASMI), muscle strength (grip strength) and 6-meter walking speed test (specific test
indicators are subject to the actual operation of each center). Among them, ASMI is detected and
calculated by dual-energy X-ray absorptiometry (DXA), and the calculation formula is ASMI =
appendicular muscle mass (kg) / height2 (m2). If the V2 visit is not assessed, then the V6 and early
withdrawal visits should also not be assessed.
19.
MDS-UPDRS includes parts I, II, III, and IV. Throughout the study, each subject should have a fixed
rater to evaluate his/her score using MDS-UPDRS.

For subjects who have received the anti-PD drug at a stable dose for at least 4 weeks prior to
study entry, the MDS-UPDRS assessment time points and corresponding assessment parts are as
follows:
Visit
MDS-UPDRS
assessment part
Assessment time points
V1
Part I
No special requirements
Part III
Before administration of background medication for PD (≥
12 hours from the most recent dose of the background
medication for PD)
V2, Early
Withdrawal
Visit (if
applicable)
Part III
Before administration of background medication for PD (≥
12 hours from the most recent dose of the background
medication for PD)
After administration of background medication for PD (to be
performed at 2 ± 1 hours after the administration of

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background medication for PD at this visit)
Parts I, II, and IV
No special requirements
V3~V6
Part III
Before administration of the investigational product and the
background medication for PD (≥12 hours from the most
recent administration of background medication for PD and
the investigational product)
After administration of the investigational product and the
background medication for PD (to be performed at 2 ± 1
hours after the administration of the background medication
for PD and the investigational product at this visit)
Parts I, II, and IV
No special requirements

For subjects who have not received the anti-PD drug at study entry, the MDS-UPDRS
assessment time points and corresponding assessment parts are as follows:
Visit
MDS-UPDRS
assessment part
Assessment time points
V1
Part I
No special requirements
Part III
No special requirements
V2
Part III
No special requirements
Parts I, II, and IV
No special requirements
V3~V6
Part III
Before administration of the investigational product (≥
12 hours from the most recent administration of the
investigational product)
After administration of the investigational product (to
be performed at 2 ± 1 hours after the administration of
the investigational product at this visit)
Parts I, II, and IV
No special requirements
Early
Withdrawal
Visit (if
applicable)
Part III
≥12 hours from the most recent administration of the
investigational product
Parts I, II, and IV
No special requirements
20.
Subjects who have early withdrawn from the study should complete the early withdrawal visit within
7 days after the investigator's awareness (if it is less than 7 days from the date of the previous visit,
repeated tests of the same item can be waived), excluding subjects who have early withdrawn from the
study due to withdrawal of consent or are lost to the follow-up.

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2 Background Information
2.1 Disease Introduction
Parkinson's disease (PD) is a degenerative neurological disease that occurs in middle-aged
and elderly individuals with insidious onset and slow progress. Its characteristic pathological
changes are progressive degeneration and decrease of dopaminergic (DA) neurons in
substantia nigra and the formation of Lewy bodies, which leads to the decrease of dopamine
transmitters in the striatum area, resulting in characteristic clinical symptoms such as
bradykinesia, resting tremor, myotonia and postural balance disorder, [1] accompanied by
various non-motor symptoms, such as olfactory dysfunction, constipation and sleep disorder [2]
and even dementia and depression. The prevalence rate of PD in individuals over 65 years old
in China is 1,700/100,000, which is similar to that in western countries.[3] It is estimated that
there are nearly 200,000 new cases of PD patients in China every year; and by 2030, the
number of PD patients in China will reach 5 million.[4] With the progression of the disease,
the motor and non-motor symptoms of PD will gradually aggravate, which will damage the
daily activities of patients themselves on the one hand, and on the other hand, it will also
bring huge social and medical burdens.
Complete and comprehensive treatments should be taken to address the motor symptoms and
non-motor symptoms of PD, including drug therapy, surgical treatment, treatment with
botulinum toxin, exercise therapy, psychological intervention, care and nursing, etc. Drug
therapy is the first choice and the main treatment approach in the whole treatment process. At
present, commonly used PD drugs available at home and abroad include levodopa, dopamine
receptor agonists, anticholinergic drugs, amantadine, monoamine oxidase type B inhibitors
and catechol-O-methyltransferase inhibitors, but none of these drugs can delay or prevent the
development of the disease. In addition, long-term use of these drugs may reduce the efficacy
of the drugs and increase the risk of complications.[5] Moreover, it is possible that these drugs
cannot achieve the dose of monotherapy required to control the symptoms due to the
corresponding treatment-limiting side effects. However, anti-PD drugs especially levodopa
and high-dose dopamine receptor agonists should not be discontinued abruptly, so as to avoid
the occurrence of malignant withdrawal syndrome.[6] Therefore, discovering new anti-PD
treatment drugs will help to break through the current bottleneck in the medical practice and
provide more new treatment options for PD patients.
Mitochondrial dysfunction and oxidative stress are the main pathogenesis of PD, and have
become the important therapeutic targets for PD in recent years. There are a large number of

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enlarged and edematous mitochondria in neurons of animal models of PD, which indicates
that the pathogenesis of PD is related to abnormal function and failure in clearance of
mitochondria. These abnormally accumulated mitochondria can also cause oxidative stress
and increase in toxic burdens, which in turn leads to the death of dopaminergic neurons and
ultimately leads to the occurrence of PD.[7, 8] In addition, with the increase in age, iron slowly
accumulates in the microglia of brain neurons, and microglia can quickly accumulate and
release iron. High iron content in cells may cause oxidative stress, thus changing the
mitochondrial autophagy function, and the expression of Parkin protein can reverse this effect.
[9] From the perspective of PD patients themselves, the mitochondria in the central nervous
system of PD patients undergo morphological changes and functional loss, and the
mitochondrial autophagy function of their substantia nigra and amygdala is also defective. [10]
Studies have demonstrated that neurons of PD patients with Parkin mutation showed
mitochondrial defects and metabolism disorder of mitochondrial deoxyribonucleic acid
(mtDNA), and Parkin can also protect midbrain neurons from neuroinflammation and
degeneration.[11] Therefore, targeting PINK1/Parkin-mediated mitochondrial autophagy has
emerged as a promising therapeutic approach to treat PD.[12]
2.2 Introduction to TJ0113 Capsules
TJ0113 capsules is an innovative mitochondrial autophagy inducer developed by Hangzhou
PhecdaMed Co., Ltd., which is enriched onto the mitochondrial outer membraneby interacting
with the myeloid cell leukemia 1 (Mcl-1) protein on the mitochondrial outer membrane.
Under the circumstance of mitochondrial damage, high concentration of reactive oxygen
species (ROS) will accumulate around mitochondria. TJ0113 can bind to the ROS and induces
the elevation of Parkin transcriptional level, mediates the enrichment of Parkin to the
damaged mitochondria, initiates mitochondrial autophagy, selectively clears damaged
mitochondria, and does not affect normal mitochondria, thus restoring cellular homeostasis.
The proposed indication of TJ0113 capsules is PD.
2.3 Summary of Non-clinical Studies
Pharmacological, pharmacokinetic (PK) and toxicological studies have been conducted with
TJ0113. The selective
induction
of mitochondrial
autophagy
by TJ0113 has
been
demonstrated in a series of pharmacological studies. The therapeutic potential of TJ0113 for
PD has been observed in an in vivo model of PD. The non-clinical studies of TJ0113 are
sufficient to support the conduct of clinical trials for PD.
This section will summarize the non-clinical studies of TJ0113, and detailed study results are

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provided in the Investigator's Brochure.
2.3.1 Non-clinical Pharmacology
The results of the in vitro pharmacology studies conducted with TJ0113 are summarized
below:

In the in vitro surface plasmon resonance assay, TJ0113 could specifically bind
to Mcl-1 protein with an affinity constant of 1.12 E-06M, representing the weak
binding.

TJ0113 selectively induced autophagy in damaged mitochondria in HEK293T
cells in vitro. TJ0113 at different concentrations (0 μM, 2.5 μM, 5 μM, 10 μM)
could selectively induce autophagy in damaged mitochondria with good dose
relationship and selectivity.

In vitro immunoblot assay, TJ01-013 demonstrated strong selectivity for
inducing mitochondrial autophagy.

In the microplate imaging assay, TJ0113 had no impact on mitochondrial
membrane potential of HEK293T cells, indicating that TJ0113 did not damage
mitochondria or cause changes in proton concentrations inside and outside
mitochondria.

The results of in vitro cell transfection assays showed that TJ0113 alone did not
cause Parkin-dependent mitochondrial autophagy in HEK293T cells, but TJ0113
could activate Parkin when mitochondria were damaged by carbonylcyanide-3-
chlorophenylhydrazone (CCCP) to induce mitochondrial autophagy and eliminate
damaged mitochondria.

In the in vitro fluorescence quantitative polymerase chain reaction (PCR) assay,
TJ0113 could increase the transcriptional level of mitochondrial autophagy genes in
the case of mitochondrial damage caused by CCCP, thereby inducing mitochondrial
autophagy.
The results of the in vivo pharmacology studies conducted with TJ0113 are summarized
below:

The pharmacodynamic study of TJ0113 (10 mg/kg, 30 mg/kg, 60 mg/kg) on 1-
methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) (Day 1-2:10 mg/kg, Day 3-
4:15 mg/kg, Day 5-6:20 mg/kg, Day 7-20:25 mg/kg) induced mouse PD model:
TJ0113 inhibited MPTP-induced behavioral damage in a dose-dependent manner,

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slowed down the dopamine neuronal loss in substantia nigra (SN) brain region,
improved nerve ending injury of dopaminergic neurons in striatum (Str) brain region,
reduced inflammatory response in the SN and Str brain region, and increased the
content of DA neurotransmitters in the Str brain region. In addition, electron
microscopy results suggest that TJ0113 could improve the reduction of number and
structural abnormalities of mitochondria in SN brain regions.

The pharmacodynamic study of TJ0113 (5 mg/kg, 15 mg/kg, 30 mg/kg) on 6-
Hydroxydopamine (6-OHDA)-induced rat PD model: TJ0113 inhibited behavioral
damage induced by 6-OHDA in a dose-dependent manner, slowed down the
dopamine neuronal loss in SN brain region, improved nerve ending injury of
dopaminergic neurons in Str brain region, reduced inflammatory response in SN and
Str brain regions, reduced the content of inflammatory factors in cerebrospinal fluid,
and increased the content of DA neurotransmitters in Str brain region.
The results of the secondary pharmacodynamic studies conducted with TJ0113 are
summarized below:

Radioligand binding and enzymatic study: TJ0113 (10 μM) inhibited the activity of
cyclooxygenase (COX)-2 at an inhibition rate of 89%. No COX-2-related toxicity
manifestations were observed in safety pharmacology studies or toxicology studies.

The off-target effect of compound TJ0113 on drug-dependent related targets in vitro
was evaluated in vitro. The study results showed that the test article TJ0113 had no
obvious agonistic or inhibitory effect on the 20 targets of G-protein-coupled receptor
(GPCR) and ion channel at 10 μM, and the agonistic or inhibitory rates were all less
than 50%.
The results of the safety pharmacology studies conducted with TJ0113 are summarized below:

The safety of TJ0113 on the central nervous system was evaluated in SD rats. The
results showed that following the single oral gavage administration of TJ0113 to SD
rats at doses of 50, 100, 200 mg/kg, TJ0113 when dosed at 200 mg/kg had no
significant impact on the central nervous system of the animals.

The safety of TJ0113 on the cardiovascular system and respiratory system was
evaluated in Beagle dogs. The results showed that single oral gavage administration
of TJ0113 to Beagle dogs at doses of 5, 15, and 30 mg/kg had no significant impact
on the cardiovascular system, respiratory system, or body temperature of the
animals.

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2.3.2 Non-clinical Pharmacokinetics
2.3.2.1 Absorption
In SD rats, following a single oral gavage and intravenous administration of TJ0113, PK
profiles including rapid absorption, low apparent volume of distribution, and moderate
elimination rate were noted. Following a single oral gavage administration of 10, 30, and 90
mg/kg in SD rats, the plasma exposure of unchanged TJ0113 increased with the increasing
dose in a less-than dose proportional manner. Following the oral gavage administration at 30
mg/kg once daily for 7 consecutive days to rats, steady state was reached on Day 4. Compared
with the oral gavage administration on Day 1, the maximum concentration (Cmax), the area
under the plasma concentration-time curve from time 0 to 24 h post-dose (AUC0-24h) and the
time to maximum concentration (Tmax) were basically unchanged on Day 7, and the half-life
(t1/2) showed a decreasing trend, suggesting that there was no obvious accumulation following
the oral gavage administration once daily for 7 consecutive days, but there was a trend of
rapid elimination. Following a single intravenous dose, the steady-state volume of distribution
(Vss) was 184 mL/kg, suggesting a relatively lower tissue distribution of TJ0113. Compared to
intravenous injection of TJ0113 at a same dose, the absolute bioavailability of unchanged
TJ0113 was 9.55% following a single oral gavage administration of the drug at 10 mg/kg to
SD rats.
In Beagle dogs, following the single oral gavage and intravenous administration of TJ0113,
the unchanged drug showed a PK profile of rapid absorption, lower apparent volume of
distribution, and rapid elimination. Following the single oral gavage administration of 3, 10
and 30 mg/kg in Beagle dogs, the plasma exposure of unchanged TJ0113 increased with
increasing dose in an approximately dose-proportional manner. Following the oral gavage
administration at 10 mg/kg once daily for 7 consecutive days in dogs, steady state was
reached on Day 4. Compared with the oral gavage administration on Day 1, the Cmax, AUC0-
24h, Tmax, and t1/2 remained substantially unchanged on Day 7, suggesting that there was no
significant accumulation following the oral gavage administration once daily for 7
consecutive days. Following a single intravenous administration in Beagle dogs, the Vss was
195 mL/kg, suggesting a low degree of tissue distribution of TJ0113. Compared to
intravenous injection of TJ0113 at a same dose, the absolute bioavailability of unchanged
TJ0113 was 9.47% following a single oral gavage administration of the drug at 3 mg/kg to
Beagle dogs.
In the in vitro study with Caco-2 cell model, the apparent permeability coefficient of TJ0113

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in the uptake direction of Caco-2 model were <0.116×10−6, 0.00934×10−6, and 0.00951×10−6
cm·s−1 at the concentrations of 1, 10, and 100 μM, respectively, all of which were lower than
the accompanying fluorescein (0.348×10−6 cm·s−1), suggesting that TJ0113 had very low
intestinal permeability. The efflux ratios of TJ0113 were > 2.84, 26.7, and 15.1 at the
concentrations of 1, 10, and 100 μM, respectively, all of which were greater than 2. After the
addition of P-glycoprotein (P-gp) inhibitor quinidine, the efflux ratio was 8.66. Compared
with the results at the absence of the inhibitor, drug efflux could be inhibited to some extent,
but the efflux ratio was still significantly greater than 2, suggesting that TJ0113 may be a
substrate of other efflux transporters besides being a weak substrate of efflux transporter P-gp.
2.3.2.2 Distribution
In the plasma protein binding study of TJ0113, the plasma protein binding rate of TJ0113 in
ICR mice, SD rats, Beagle dogs, cynomolgus monkeys and humans was separately
determined to evaluate whether there was a concentration dependence as well as to compare
the inter-species differences in plasma protein binding rates. The results showed that, within
the concentration range of 0.5-15 μg/mL, the plasma protein binding rate of TJ0113 didn’t
demonstrate significant concentration dependence in the five species. Based on the different
plasma concentrations of all the species, the average binding rates calculated were 99.2 ±
0.110% in mice, 99.9 ± 0.00188% in rats, 98.0 ± 0.0935% in dogs, 99.6 ± 0.0395% in
monkeys, and 99.6 ± 0.0223% in humans, respectively.
In the whole blood-to-plasma concentration partition ratio study of TJ0113, the whole blood-
to-plasma partition coefficients of TJ0113 in CD-1 mice, SD rats, Beagle dogs, cynomolgus
monkeys and healthy humans were determined, and the inter-species differences were
compared. The results showed that within the concentration range of 0.4-40 μg/mL, the mean
whole blood-to-plasma partition coefficients of all the species at different concentrations were
0.575 (mouse), 0.678 (rat), 0.490 (dog), 0.636 (monkey), and 0.554 (human), respectively,
suggesting that within the concentration range of 0.4-40 μg/mL, TJ0113 had a low distribution
in the whole blood of mice, rats, dogs, monkeys and humans, and there was no significant
concentration dependence or species differences.
According to the tissue distribution study of TJ0113 following the oral gavage administration
in rats, following a single oral administration of TJ0113 at 30 mg/kg, the gastric and intestinal
concentrations were the highest at 0.167 h post-dose; the Tmax of distribution in the brain, fat,
heart, muscle, liver, spleen, kidneys, lungs, uterus and ovary tissues was basically the same as
that in the plasma, reaching the peak distribution at 1 h, and that in the testicular tissue lagged

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behind the Tmax in the plasma. At 12 h post-dose, the content of TJ0113 in tissues all
decreased to less than 1/10 of Cmax. The distribution of TJ0113 in all the other tissues except
the gastric tissue was all less than that in the plasma, which was consistent with the low
apparent volume of distribution presented in the kinetics studies in the plasma. According to
the AUC0-12h data of TJ0113 in all the tissues, the exposure in the tissues was ranked in the
following order: stomach (8.60 times of that in plasma) > plasma > liver, intestine, kidney
(30% to 50% of that in plasma) > ovary, lung, uterus, heart (10% to 20% of that in plasma) >
testis, spleen, muscle, fat and brain (1% to 10% of that in plasma).
2.3.2.3 Metabolism
In addition to the unchanged TJ0113, 2, 4, 2, 4 and 3 metabolites were identified in the
hepatocyte incubation systems of mice, rats, dogs, monkeys and humans, respectively. The
metabolic pathways included dehydration, dealkylation, dehydro-oxidation, hydroxylation,
sulphating, glutamate binding and the combination of different metabolic pathways. The main
metabolites in the hepatocytes of all the species were unchanged TJ0113 and M4
(dealkylation + hydroxylation + dehydro-oxidation).
In mouse, rat, dog, monkey and human liver microsome incubation systems, 3, 3, 2, 2 and 2
metabolites were identified, respectively, in addition to the unchanged drug TJ0113. The
major metabolic pathways were mediated by glucuronic acid conjugation, desulfoxidation +
glucuronic acid conjugation, and desulfoxidation + monooxidation + glucuronic acid
conjugation. The main metabolites in the liver microsomes of humans, monkeys and dogs
were M23 (desulfoxidation + glucuronic acid conjugation) and M33 (desulfoxidation+
monooxidation + glucuronic acid conjugation), and none of them responded to the UV except
for the unchanged drug; The main metabolites of rat and mouse liver microsomes are M26
(glucuronidation), M23 and M33, and none of them responded to the UV except for the
unchanged drug.
After TJ0113 (1 μM) was incubated in hepatocytes of all the species for 180 min, the residual
substrate rates were 112% (monkey), 111% (dog), 98.3% (rat), 66.1% (human), and 44.0%
(mouse), respectively. TJ0113 had no significant metabolic elimination in the hepatocytes of
rats, monkeys and dogs. Metabolic elimination occurred in mouse and human hepatocytes to
some extents, with the elimination half-lives of 151 and 252 min, respectively.
Based on the in vitro study of human cytochrome P450 (CYP450) enzyme phenotyping,
combined with the results of the study of liver microsome binding to chemical inhibitors and
recombinant monomeric enzymes, it showed that TJ0113 was basically not metabolized by

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CYP450 enzymes, indicating that human CYP450 enzymes are not the main enzymes
involved in the metabolic transformation of TJ0113.
TJ0113 and metabolite M23 (dealkylation + glucuronidation) were the main exposure forms
in the circulatory system following the oral gavage administration in rats, and unchanged
TJ0113 was the main exposure substance in the circulatory system following the oral gavage
administration in dogs. In addition to the unchanged drug, a total of 7 metabolites were
detected in the urine of rats following a single oral gavage administration (30 mg/kg). Among
them, the unchanged drug and metabolites M12 (dehydroxylation + glucuronic acid
conjugation), M15 (dehydroxylation), M26 (glucuronic acid conjugation), and M29 (glucose
conjugation) were the main forms of excretion, with the cumulative excretion fractions of
0.552%, 0.500%, 0.752%, 0.638%, and 0.385%, respectively. In addition to the unchanged
drug, a total of 12 metabolites were found in rat feces, among which the unchanged TJ0113,
M15 (dehydroxylation) and M4 (dealkylation + hydroxylation + dehydro-oxidation) were the
main forms of excretion, and the cumulative excretion fractions were 8.82%, 13.3% and
8.61%, respectively. In addition to the unchanged drug, a total of 14 metabolites were found
in rat bile, among which the unchanged TJ0113 and M4 (dealkylation + hydroxylation +
dehydro-oxidation) were the main forms of excretion, and the cumulative excretion fractions
were 2.10% and 1.17%, respectively. The total amount of TJ0113 excreted through urine and
feces in the unchanged form and all the metabolite forms was 3.14% and 35.8% of the
administered dose, respectively, and the mass balance coefficient was 38.94%. TJ0113 was
mainly excreted in the urine through the kidneys in the unchanged form and metabolites M12
(dehydroxylation + glucuronic acid conjugation), M15 (dehydroxylation), M26 (glucuronic
acid conjugation), and M29 (glucose conjugation); It was excreted in the feces through the
intestines in unchanged form and in the form of metabolites M15 (dehydroxylation) and M4
(dealkylation + hydroxylation + dehydro-oxidation). Based on the current result set and
combined with the results of excretion studies, it is suggested that TJ0113 is primarily
eliminated in metabolic form, and the main excretion route is the intestinal tract.
In the metabolite profiling study of the first and last plasma samples collected following the
repeated oral gavage administration of TJ0113 in SD rats and Beagle dogs, the first dose
plasma exposure profile analysis showed that after repeated oral gavage administration of 200
mg/kg TJ0113 to SD rats, in addition to the unchanged drug, 17 metabolites were identified in
the plasma on D1. The unchanged drug (female 35.5%/male 38.7%), metabolite M6
(dehydrogenation: female 12.1%/male 16.8%) and metabolite M15 (deoxygenation: female

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23.0%/male 11.5%) were the main exposure forms, and the remaining metabolites accounted
for 0.0245% to 9.21% of the total related substances. Following repeated oral gavage
administration of 100 mg/kg TJ0113 to Beagle dogs, in addition to the unchanged drug, a total
of 16 metabolites were identified in the plasma on D1. The unchanged drug (female
35.0%/male
31.6%),
metabolite
M6
(dehydrogenation:
female
19.4%/male
17.6%),
metabolite M5 (desulfoxidation + sulphation: female 10.1%/male 12.9%) and metabolite M37
(deoxidation + decarbonization: female 10.7%/male 12.6%) were the major exposure forms in
plasma of Beagle dogs. The remaining metabolites accounted for 0.222% to 7.66% of total
related substances. According to analysis results of plasma exposure profile after the last dose:
In addition to the unchanged drug, 21 metabolites were identified in plasma on D91 following
repeated intragastric administration of 200 mg/kg TJ0113 to SD rats. The unchanged drug
(female 21.7%/male 24.9%), metabolite M6 (dehydrogenation: female 7.71%/male 10.9%),
metabolite M39 (S-dealkylation + oxidation: female 13.2%/male 11.8%) and metabolite M15
(deoxygenation: female 22.5%/male 19.6%) were the main exposure forms, and the remaining
metabolites accounted for 0.0197% to 7.71% of the total related substances. Following the
repeated oral gavage administration of 100 mg/kg TJ0113 to Beagle dogs, in addition to the
unchanged drug, a total of 20 metabolites were identified in the plasma on D91. The
unchanged drug (female 28.4%/male 31.1%), metabolite M6 (dehydrogenation: female
15.8%/male 17.2%), metabolite M5 (desulfoxidation + sulphation: female 12.3%/male 11.0%)
and metabolite M37 (deoxidation + decarbonization: female 11.6%/male 11.0%) were the
major exposure forms in plasma of Beagle dogs. The remaining metabolites accounted for
0.0467% to 6.62% of total related substances.
2.3.2.4 Excretion
Following a single oral gavage dose of TJ0113 30 mg/kg in SD rats, the proportions of
TJ0113 excreted as unchanged in feces (8.85%) > bile (2.11%) > urine (0.552%), and the total
fraction of TJ0113 excreted as unchanged in urine and feces was 9.40%, suggesting that
TJ0113 was eliminated in vivo mainly in the form of metabolism.
2.3.2.5 Drug Interactions
TJ0113 may cause CYP induction in vitro and, therefore, may reduce exposure levels to drugs
metabolized by CYP enzymes. The in vitro induction of human CYP450 enzymes by TJ0113
showed that within the concentration range of 0.2-10 μM, TJ0113 did not significantly induce
the expression of CYP1A2, CYP2B6, and CYP3A4 messenger ribonucleic acid (mRNA) in
human hepatocytes from the two donors of HUB and BEI; TJ0113 showed a concentration-

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dependent induction effect on the expression of CYP1A2, CYP2B6, and CYP3A4 mRNA in
human hepatocytes from Lhuf15906 donors within the concentration range of 1-10 μM.
The in vitro inhibitory effect study of TJ0113 on human CYP450 enzymes showed that
following the administration of TJ0113, the half inhibitory concentrations (IC50) for CYP1A2,
CYP2D6 and CYP3A4 (midazolam and testosterone as substrates) were greater than 50 μM,
and the IC50 for CYP2B6, CYP2C8, CYP2C9 and CYP2C19 were 23.1 μM, 24.7 μM, 10.8
μM and 38.3 μM, respectively, and there was no significant inhibitory effect on all the CYP
enzyme isoforms.
TJ0113 had very low intestinal permeability and may be a substrate for other efflux
transporters in addition to being a weak substrate for the efflux transporter P-gp. In addition,
MDCK-OAT1 and HEK293-URAT1 cell lines were used to study the inhibitory effect of
TJ0113 on organic anion transporter 1 (OAT1) and urate transporter 1 (URAT1), and the
transport effect of transporters OAT1 and URAT1 on TJ0113. The study results showed that
TJ0113 inhibited transporter OAT1 significantly, with an IC50 of 4.32 μM; there was no
significant inhibitory effect on transporter URAT1, with an IC50 greater than 30 μM. TJ0113
was not a substrate of transporter OAT1, and it might be a substrate of transporter URAT1.
2.3.3 Toxicology
2.3.3.1 Single-dose Toxicity Studies
In SD rats, following the single oral administration of 500, 1,000, and 1,500 mg/kg of TJ0113,
no abnormalities were found in the cage-side observation in each group on the day of
administration (D0). During the observation period, animal No. 28 (F) developed piloerection
symptoms from D1-D2 of the observation period, and recovered on D3. No abnormality was
found in the cage-side observations of other animals. During the study period, the body
weight gain of animals in each dose group was normal. At the end of the observation period,
all surviving animals were subjected to gross dissection, and there were no abnormalities in
the volume, color and texture of heart, liver, kidney, spleen, lung, gastrointestinal tract and
other organs.
Following the single oral administration of 500, 1,000, and 1,500 mg/kg TJ0113 to Beagle
dogs, all the animals in the dose groups survived to the end of the study. During the study, no
significant abnormality was observed in the animals of the vehicle control group. Following
the administration on D0, except the female animals in the 500 mg/kg dose group, all other
animals showed vomiting symptoms, and individual animals had loose stools. From D1 to
before dissection, loose stools and vomiting were occasionally observed in male animals in

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the 1,000 mg/kg and 1,500 mg/kg dose groups, while no obvious abnormalities were observed
in other animals. During the study, there was no obvious abnormality in the body weight or
body temperature of all animals in the dose group. On Day 14 after administration, there were
no obvious abnormalities in the ECG parameters such as heart rate, PR interval, QRS interval
and QT interval in all animals in the dose groups. At the end of the observation period, there
were no obvious abnormalities in hematology, serum chemistry, and coagulation parameters
of all animals in the dose groups. At the end of the observation period, all animals were
subjected to gross dissection, and no obvious abnormalities were found in the heart, liver,
kidney, spleen, lung, gastrointestinal tract or the administration site.
The maximum tolerated dose of TJ0113 was greater than 1,500 mg/kg following the single
oral gavage administration to SD rats and greater than 1,500 mg/kg following the single oral
administration to Beagle dogs, and TJ0113 was generally well tolerated.
2.3.3.2 Repeat-dose Toxicity Studies
TJ0113 was given to SD rats via intragastric route for 4 consecutive weeks at doses of 30, 100,
and 300 mg/kg/day, respectively. The results showed that there were changes in hematology
and serum chemistry parameters in each dose group of TJ0113, but these changes were not
considered toxicologically significant, and completely reversible at the end of the recovery
period. The renal coefficient of female rats in the 300 mg/kg/day dose group was higher than
that in the vehicle control group, and it was reversible at the end of the recovery period.
Histopathological results showed that test article-related pathological changes were seen in
the kidneys of male rats, mainly manifested as basophilic lesions of renal tubules, which were
not completely reversible at the end of the recovery period. No obvious test article-related
pathological changes were observed in the kidneys of female rats in each dose group.
Following the repeated oral gavage administration of TJ0113, exposure in SD rats increased
with increasing dose. After the last dose, the exposure in female and male SD rats in the 30
and 100 mg/kg/day dose groups was significantly lower than that at the first dose. There was
no gender difference in the exposure of each dose group in SD rats. The NOAEL following
the oral gavage administration of TJ0113 to SD rats for 4 consecutive weeks was 100 mg/kg.
At this dose, the last Cmax was 11,906 ng/mL (male) and 11,144 ng/mL (female), respectively
and the area under the plasma concentration-time curve from time zero to time t (AUC0-t) was
66,728 h*ng/mL (male) and 43,818 h*ng/mL (female), respectively.
Following the repeated oral administration of TJ0113 to Beagle dogs at doses of 10, 30, and
100 mg/kg/day (at a dose volume of 5 mL/kg) once daily for 28 consecutive days followed by

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a 28-day recovery period. There were no test article-related toxicity changes in general
physiological parameter, clinical pathology, and histopathological examinations. The NOAEL
following the 4-week repeat doses of TJ0113 to Beagle dogs was 100 mg/kg. On Day 28, the
AUC0-t was 42,847 ± 17,551 h*ng/mL for males and 51,542 ± 14,505 h*ng/mL for females,
respectively.
No test article-related abnormal changes in each parameter were observed following
intragastric administration of TJ0113 at 30, 80, and 200 mg/kg/day to SD rats for 13
consecutive weeks. TJ0113 was given to SD rats via intragastric route for 13 consecutive
weeks. The NOAEL in SD rats was 200 mg/kg. At this dose, the Cmax in SD rats was 17.8 ±
4.86 μg/mL (female) and 11.2 ± 1.99 μg/mL (male), and the AUC0-24h was 92.7 ± 34.1
h·μg/mL (female) and 63.3 ± 10.9 h·μg/mL (male), respectively.
Beagle dogs were given 10, 30, 100 mg/kg TJ0113 by intragastric route for 13 consecutive
weeks. The main test article-related symptoms were as follows: (1) Soft stools, loose stools
and vomiting were observed in the animals of each dose group, and gastrointestinal reactions,
such as watery stools and red liquid in stools, were observed occasionally, which recovered
significantly after drug withdrawal. (2) Individual male animals in the ≥30 mg/kg dose
groups showed decreased activity, and one male animal in the 100 mg/kg dose group
developed slight mental depression. No obvious abnormal changes were observed in body
weight, food consumption, clinical laboratory tests, organ weight and coefficient, and
histopathology. The NOAEL of TJ0113 following the oral gavage administration for 13
consecutive weeks to beagle dogs was 100 mg/kg. At this dose, Cmax in female and male dogs
after the last dose was 6.50 ± 1.59 and 6.02 ± 0.933 μg/mL, respectively, and AUC0-24h was
25.3 ± 8.19 and 23.0 ± 2.58 h·μg/mL, respectively. There was no significant sex difference or
remarkable accumulation in vivo after continuous administration.
2.3.3.3 Genotoxicity
The results of genotoxicity study showed that TJ0113 exhibited no mutagenic effect on strains
TA97a, TA98, TA100, TA102 and TA1535 within the dose range of 128-5,000 μg/dish under
activated and non-activated conditions. Under non-activated or S9 activated conditions,
TJ0113 did not increase the chromosome aberration of CHL cells within the concentration
range of 3-12 μg/mL. Following the oral gavage administration of TJ0113 at 500, 1,000, and
2,000 mg/kg to the ICR mice, no effect of inducing an increase in micronucleus rate of bone
marrow polychromatic erythrocytes was observed. TJ0113 had no mutagenic effect.

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2.3.3.4 Reproductive Toxicity
TJ0113 at doses of 30, 80 and 200 mg/kg had no significant systemic toxicity to both male
and female parental rats, and no significant toxicity to fertility and early embryonic
development of rats. The NOAEL of TJ0113 for both male and female parental rats and early
embryonic development was 200 mg/kg.
After intragastric administration of TJ0113 at doses of 30, 100 and 300 mg/kg to pregnant rats
from GD6 to GD17, 30 and 100 mg/kg TJ0113 had no obvious systemic toxicity to pregnant
rats; weight gain of parental pregnant rats in the 300 mg/kg dose group decreased. The
NOAEL of TJ0113 for parental female rats was 100 mg/kg. At this dose, Cmax of the
unchanged drug in maternal rats was 14.1±1.47 μg/mL and AUC0-24h was 107±32.0 h·μg/mL.
TJ0113 at the dose of 30 mg/kg had no significant effect on fetal growth and skeletal
development, while TJ0113 at 100 and 300 mg/kg had an impact on fetal growth and skeletal
development. The NOAEL for embryo-fetal development was 30 mg/kg. At this dose, Cmax of
the unchanged drug in maternal rats was 6.44 ± 0.87 μg/mL and AUC0-24h was 36.2 ± 18.5
h·μg/mL.
After intragastric administration of TJ0113 at doses of 10, 30 and 100 mg/kg to New Zealand
rabbits from GD6 to GD19, TJ0113 at the doses of 10 and 30 mg/kg had no obvious systemic
toxicity to parental female rabbits. TJ0113 when dosed at 100 mg/kg had an impact on
fertility of parental rabbits. The NOAEL of TJ0113 for parental rabbits was 30 mg/kg. At this
dose, Cmax of the unchanged drug in maternal rabbits was 0.427±0.103 μg/mL and AUC0-24h
was 0.842±0.116 h·μg/mL. TJ0113 when dosed at 10, 30 and 100 mg/kg had no obvious
toxicity to fetal growth and skeletal development. The NOAEL for embryo-fetal development
was 100 mg/kg. At this dose, Cmax of the unchanged drug in maternal rabbits was 0.899 ±
0.584 μg/mL, and AUC0-24h was 2.28 ± 1.00 h·μg/mL.
2.4 Summary of Clinical Trials of TJ0113 Capsules
2.4.1 Trial Design
A phase I clinical trial to evaluate the safety, tolerability and pharmacokinetics of single dose,
multiple doses of TJ0113 capsules and oral dose of TJ0113 capsules under fed conditions in
healthy subjects (registration number: CTR20232426) has been completed. This study
consisted of a single ascending dose (SAD) study, a multiple ascending dose (MAD) study,
and a high-fat diet food effect (FE) study.
A total of 6 dose groups (A1 to A6) were set up in the SAD study, namely 80 mg, 160 mg,
260 mg, 400 mg, 540 mg and 720 mg dose groups, respectively. A total of 72 healthy adult

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subjects (12 subjects/group), including men and women, were enrolled at this stage. Subjects
in each dose group were randomized in a 5:1 ratio to receive either investigational drug
TJ0113 capsules or placebo (10 of whom received study drug and 2 received placebo). Two
subjects in the 80 mg dose group were assigned as the sentinel group and were randomly
assigned to receive TJ0113 capsules or placebo in a 1:1 ratio. The remaining 10 subjects in the
80 mg dose group were randomly assigned to receive either TJ0113 capsules or placebo in a
9:1 ratio after completion of the 24-h post-dose safety observation in the sentinel group.
A total of three dose groups (B1 to B3) were set up in the MAD study, namely, 200 mg once
daily (QD), 400 mg QD, and 300 mg twice daily (BID) dose groups. A total of 36 healthy
adult subjects (12/group), including men and women, were enrolled. Subjects in each dose
group were randomized in a 5:1 ratio to receive either investigational drug TJ0113 capsules or
placebo (10 of whom received study drug and 2 received placebo). The drugs were orally
administered with warm water for 7 consecutive days (only once in the morning on Day 7).
The FE study adopted a single-center, single-dose (200 mg), randomized, open-label, 2-
sequence, 2-period, crossover design, in which a total of 20 healthy adult subjects were
randomly assigned in a 1:1 ratio to 2 dosing sequences (C1: fasting-after a meal; C2: after a
meal-fasting) with 10 subjects in each group (all of them were orally administered with study
drug TJ0113 capsules). Each dosing sequence consisted of 2 periods, and the drugs were
administered once in each period. In Group C1, the drugs were administered under a fasted
state in Period I and after a meal in Period II; and in Group C2, the drugs were administered
after a meal in Period I and under a fasted state in Period II. There was an interval of 7 days
(the washout period between two doses) between the two periods.
2.4.2 Trial Results
A total of 562 subjects were screened in the phase I study, and 130 (23.1%) subjects were
eligible at the screening and were randomized. Among them, 74, 36 and 20 subjects were
enrolled in the SAD, MAD and FE studies, respectively, and completed the studies (2 subjects
in the SAD study were withdrawn early at the investigator's discretion and did not use the
investigational drug). The population enrolled in this study was homogeneous, and the main
demographic characteristics were relatively balanced between the investigational drug group
and the placebo group.
The results of the PK analysis are summarized below:

After a single dose within the range of 80 mg to 720 mg, the Cmax (range: 967.30-
3,100.00 ng/mL) increased non-linearly along with the increasing dose in a less-than

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dose proportional manner. The average t1/2 decreased first and then increased along
with the increasing dose, mainly within the range of 3.20 to 2.24 h. The median Tmax
increased along with the increasing dose (except for 720 mg dose group), mainly
within the range of 1.50 to 2.00 h. The exposure (AUC0-last [range: 3,008.21-
15,927.76 h * ng/mL] and AUC0-inf [range: 3,027.12-16,338.11 h * ng/mL]) showed
a nonlinear increase in the 80-720 mg range in a less-than dose proportional manner,
but a linear increase in the 80-400 mg range.

After multiple dose within the range of 200 mg QD to 300 mg BID for 7 days,
Cmax,ss (1,972.00 ng/mL vs 2,115.00 ng/mL), AUC0-t,ss (7,235.06 h*ng/mL vs
9,675.24 h*ng/mL), and AUC0-inf,ss (7,399.83 h*ng/mL vs 9,907.55 h*ng/mL) in the
200 mg QD and 400 mg QD dose groups increased along with the increasing dose.
The average t1/2,ss (2.37 ± 0.338 h vs. 2.26 ± 0.378 h) and the median Tmax (2.00 vs.
1.98 h) were close for the two dose groups. The Rac(Cmax) and Rac(AUC) in the 200 mg
QD dose group were 1.21 ± 0.281 and 1.10 ± 0.184, respectively, suggesting that
TJ0113 almost had no accumulation in vivo after 200 mg QD administration. The
Rac(Cmax) and Rac(AUC) in the 400 mg QD dose group were 1.46 ± 0.422 and 1.40 ±
0.661, respectively, suggesting that TJ0113 had a slight accumulation in vivo after
400 mg QD administration. The Cmax,ss (2,323.00 ng/mL), AUC0-t,ss (11,056.15
h*ng/mL) and AUC0-inf,ss (11,412.01 h*ng/mL) in the 300 mg BID dose group were
higher than those in the other two groups. The average t1/2,ss was 2.56 ± 0.791 h, the
median Tmax was 1.50 h, and Rac(Cmax) and Rac(AUC) were 0.90 ± 0.173 and 0.86 ±
0.222, respectively, indicating that TJ0113 almost had no accumulation in vivo after
300 mg BID administration.

A high-fat diet reduced the absorption of TJ0113 in humans and delayed the
absorption of the drug in humans.

There was no significant correlation between the level of mtDNA and the dose in
healthy people.
Safety results were summarized as follows:

In the SAD study, a total of 33 subjects experienced adverse events (AEs) (28 in the
treatment group and 5 in the placebo group) and all AEs were treatment-emergent
adverse events (TEAEs). By the preferred term (PT), the top three common TEAEs
in terms of incidence (with an incidence of > 5%) were white blood cell count
decreased (9.7%), hyperuricaemia (9.7%) and neutrophil count decreased (8.3%).

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The incidences of TEAEs by each PT were similar between the treatment group and
the placebo group. A total of 31 subjects experienced adverse drug reactions (ADRs)
(26 in the treatment group and 5 in the placebo group). There were no serious
adverse events (SAEs) or AEs leading to death, and there were no grade ≥3 AEs,
ADRs, or TEAEs. The incidence of grade 2 TEAEs related to the investigational
drug in each treatment group (80 mg, 160 mg, 260 mg, 400 mg, 540 mg, and 720
mg) was 0%, 0%, 10.0%, 10.0%, 10.0%, and 0%, respectively. No dose group met
the dose termination criteria, suggesting that a single dose of TJ0113 within the dose
range of 80-720 mg was well tolerated.

In the MAD study, a total of 17 subjects experienced AEs (13 in the treatment group
and 4 in the placebo group), all of which were TEAEs. By the PT, the top three
common TEAEs in terms of incidence were white blood cell count decreased (8.3%),
neutrophil count decreased (8.3%) and hyperuricaemia (8.3%). The incidences of
TEAEs by each PT were similar between the treatment group and the placebo group.
A total of 15 subjects experienced ADRs (11 in the treatment group and 4 in the
placebo group); only one subject experienced a grade 3 TEAE (200 mg QD dose
group), and none of the remaining subjects experienced any grade ≥3 AEs, ADRs,
and TEAEs. There were no SAEs or AEs leading to death. The incidence of grade 2
TEAEs related to the investigational drug in each treatment group (200 mg QD, 400
mg QD, and 300 mg BID) was 0%, 10.0%, and 10.0%, respectively. None of the
dose groups met the dose termination criteria, suggesting that multiple doses of
TJ0113 within the dose range of 200 mg QD to 300 mg BID were well tolerated.

In the FE study, a total of 6 subjects receiving administration under fasted conditions
had AEs, all of which were TEAEs. There were 4 subjects with ADRs. One AE in a
subject who received administration under fed conditions was an TEAE and
considered to be an ADR. The incidence of TEAEs was numerically higher with
administration under a fasted state than that with the administration after a meal, and
the incidence of all TEAEs (lymphocyte count decreased, white blood cells urine
positive, neutrophil count decreased, oropharyngeal pain, dermatitis allergic, and
abdominal pain) in the FE study was 5.0% by PT. There were no SAEs or AEs
leading to death and no grade 3 and above AEs or ADRs in the FE study. The
incidence of grade 2 TEAEs related to the investigational drug occurred in the
treatment groups (fasted group and fed group) was 0% and 20.0%, respectively.

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In summary, the safety profile of TJ0113 capsules at the current dose-finding level was good,
the incidence of AEs was similar between the treatment group and the placebo group, and no
unexpected or serious safety signals have been identified.
2.5 Benefit/Potential Risk Assessment
2.5.1 Risk Assessment
Based on the results of the toxicological studies and the guidance of drug clinical trial
approval letter (No. 2023LP01405), TJ0113 capsules were generally well tolerated. The main
toxicities were gastrointestinal toxicity (vomiting, loose stools), renal toxicity (basophilic
lesions in renal tubules), hepatotoxicity (total bilirubin [TBIL] increased, liver coefficient
increased), potential impact on QT interval, and embryo-fetal reproductive toxicity, etc. Based
on the completed phase I clinical trial in healthy subjects (registration No.: CTR20232426),
the safety profile of TJ0113 capsules following the single dose administration within the dose
range of 80-720 mg, and that following the multiple dose administration at 200 mg QD, 400
mg QD, and 300 mg BID was good; the incidences of AEs were similar between the treatment
group and the placebo group, and no unexpected or serious safety signals have been identified.
In the phase II study, in order to minimize the overall risk of subjects and ensure the safety of
subjects, the following measures were taken: enrollment of appropriate subject population
based on the inclusion/exclusion criteria, conducting the screening examinations/tests
(medical history and treatment history, vital signs, physical examination, laboratory tests,
serum virology test, 12-lead electrocardiogram [ECG], etc.), and safety evaluation and
follow-up. This study will also strictly require the subjects to take highly effective
contraceptive measures and conduct regular pregnancy tests for women of childbearing
potential. In addition, all subjects will be closely monitored for clinical safety assessments
such as vital signs, laboratory tests, 12-lead ECG, etc. according to schedule of activities
(SoA). Therefore, it can be considered that the expected risks of TJ0113 capsules in the phase
II study is controllable.
2.5.2 Benefit Assessment
TJ0113 capsules is a new oral selective mitochondrial autophagy inducer developed by
Hangzhou PhecdaMed Co., Ltd., and the proposed indication under development is PD.
Based on the fact that the marketed anti-PD treatment drugs in China cannot meet the
treatment needs in large PD patient population, there is an urgent need for developing new
anti-PD treatment drugs with good efficacy and safety to provide patients with more options
and clinical benefits. Targeting PINK1/Parkin-mediated mitochondrial autophagy has

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emerged as a promising approach for the treatment of PD. TJ0113 has demonstrated its
mitochondrial autophagy effect in a series of pharmacological studies. In MPTP-induced PD
mouse model and 6-OHDA-induced PD rat model, TJ0113 was observed to improve neuronal
damage and reduce inflammation after administration, which has the potential to treat PD. In
addition, TJ0113 not only has a good effect of ROS scavenging, but also can scavenge
damaged mitochondria from the source, thus fundamentally inhibit the generation of ROS.
To sum up, TJ0113 is expected to improve the motor function of PD patients by improving
neuronal damage, repairing mitochondrial damage, reducing inflammation, and inhibiting
oxidative stress. TJ0113 capsules are expected to confer significant benefits to PD subjects in
the phase II study.
2.5.3 Benefit/Risk Assessment
Based on the safety and PK/PD profiles of TJ0113 capsules demonstrated in non-clinical and
clinical studies, TJ0113 capsules are safe and well tolerated, and it is expected to effectively
improve motor function of PD patients.
In the phase II study, the following measures will be taken to ensure the safety of subjects:
enrollment of appropriate subject population based on the inclusion/exclusion criteria,
conducting the screening examinations/tests (medical history and treatment history, vital signs,
physical examination, laboratory tests, serum virology test, 12-lead ECG, etc.), and safety
evaluation and follow-up. This study will also strictly require the subjects to take highly
effective contraceptive measures and conduct regular pregnancy tests for women of
childbearing potential, which are expected to further effectively control the risk of subjects.
To sum up, it can be considered that the benefits of subjects in the phase II study in the PD
population outweigh the risks, and the risks are manageable.

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3 Trial Objectives and Endpoints
3.1 Trial Objectives
Primary Objectives

To assess the efficacy of TJ0113 capsules in the treatment of patients with early-
stage PD.
Secondary Objectives

To assess the efficacy of TJ0113 capsules in the treatment of patients with early-
stage PD;

To assess the safety of TJ0113 capsules in the treatment of patients with early-stage
PD.
Exploratory Objectives

To explore the changes in inflammatory indicators in early-stage PD patients treated
with TJ0113 capsules;

To explore the effect of TJ0113 capsules on PD biomarkers in early-stage PD
patients;

To explore the effect of TJ0113 capsules on skeletal muscle mass and function in
early-stage PD patients;

To explore the association between the efficacy of TJ0113 capsules and the genomic
characteristics in early-stage PD patients.
3.2 Trial Endpoints
Primary Endpoints

Changes from baseline in scores of the Unified Parkinson's Disease Rating Scale
(MDS-UPDRS) Part III (motor examination) in subjects after 12 weeks of treatment.
Evaluation time point: ≥12 hours from the most recent dose of anti-PD drug.
Secondary Endpoints

Efficacy Endpoints

Changes from baseline in scores of MDS-UPDRS Part III (motor examination) in
subjects after 1, 4, 8 weeks of treatment. Evaluation time point at each visit: ≥12
hours from the most recent dose of anti-PD drug;

Changes from baseline in scores of MDS-UPDRS Part III (motor examination) in

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subjects after 1, 4, 8, 12 weeks of treatment. Evaluation time point at each visit: 2 ±
1 hours from the most recent dose of anti-PD drug;

Changes from baseline in scores of MDS-UPDRS Part I, II and IV in subjects after 1,
4, 8 and 12 weeks of treatment;

Changes from baseline in the total scores of MDS-UPDRS in subjects after 1, 4, 8,
12 weeks of treatment, including:
-
Total score 1: II+III; wherein, the evaluation time point for MDS-UPDRS Part
III (motor examination) is ≥12 hours from the most recent dose of anti-PD drug;
-
Total score 2: II+III; wherein, the evaluation time point for MDS-UPDRS Part
III (motor examination) is 2 ± 1 hours from the most recent dose of anti-PD
drug;
-
Total score 3: I+II+III; wherein, the evaluation time point for MDS-UPDRS Part
III (motor examination) is ≥12 hours from the most recent dose of anti-PD drug;
-
Total score 4: I+II+III; wherein, the evaluation time point for MDS-UPDRS Part
III (motor examination) is 2 ± 1 hours from the most recent dose of anti-PD
drug;
-
Total score 5: I+II+III+IV; wherein, the evaluation time point for MDS-UPDRS
Part III (motor examination) is ≥12 hours from the most recent dose of anti-PD
drug;
-
Total score 6: I+II+III+IV; wherein, the evaluation time point for MDS-UPDRS
Part III (motor examination) is 2 ± 1 hours from the most recent dose of anti-PD
drug.

Safety Endpoints

AE;

Laboratory test;

Vital signs

Physical examination;

12-lead ECG.

Exploratory Endpoint

Changes from baseline in inflammatory indicators after 4, 8, 12 weeks of treatment;

Changes from baseline in α-synuclein and glial fibrillary acidic protein (GFAP) after

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12 weeks of treatment;

Changes from baseline in appendicular skeletal muscle mass index (ASMI)
measured by dual-energy X-ray absorptiometry (DXA) after 12 weeks of treatment;

Changes from baseline in muscle strength (grip strength) after 12 weeks of treatment;

Changes from baseline in 6-meter walking speed test after 12 weeks of treatment.

The association between the efficacy of TJ0113 capsules and the genomic
characteristics in early-stage PD patients.

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4 Selection and Withdrawal of Subjects
4.1 Inclusion Criteria
Subjects who meet all of the following criteria will be eligible for this study:
1.
Subjects who voluntarily participate in the clinical trial, and have signed the informed
consent form (ICF), are able to understand and follow the study protocol, willing to visit
the study site on time, fully understand the content, process and potential adverse
reactions of the study, and indicate the date of signing the ICF;
2.
Males or females aged 30-80 years (both inclusive) at the time of signing the ICF;
3.
Subjects who are diagnosed with PD according to the Diagnostic Criteria for Parkinson's
Disease in China (2016 edition);
4.
The scores of modified Hoehn and Yahr Scale at screening are 1-2.5 (both inclusive);
5.
Subjects who have not previously received anti-PD drugs; or those who have previously
used any anti-PD drugs but have not received such drug within 4 weeks before study
entry; or those who have received the anti-PD drug at a stable dose for at least 4 weeks
before study entry and agree to maintain the original treatment regimen during the study;
6.
Subjects with the scores of MDS-UPDRS Part III of ≥22 at screening (it should be
scored ≥12 hours apart from the most recent dose of the anti-PD drug for subjects who
have been receiving an anti-PD drug at a stable dose for at least 4 weeks prior to study
entry);
7.
Subjects of childbearing potential (including spouses of male subjects) who have no
childbearing or sperm donation plan from the end of the screening period to within 6
months after the last dose and are willing to use at least one effective method (see
Appendix I for details) for contraception.
4.2 Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from this study:
1.
Presence of any medical condition that may interfere with full participation in the study,
including but not limited to the following: medical history of epilepsy or any
complications, medical history of hemolytic anemia, pulmonary embolism, respiratory
depression, active psychiatric disease, or malignancy; positive tumor marker detection
results at screening and judged by the investigator to be clinically significant;
2.
Subjects who have experienced a New York Heart Association (NYHA) Class III or
above congestive heart failure, unstable angina pectoris, acute myocardial infarction,

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hemorrhagic stroke (stroke), and ischemic stroke (including transient ischemic attack)
within 6 months before screening; or those who have undergone any percutaneous
coronary intervention or coronary artery bypass grafting, heart valve repair/replacement;
or those with severe arrhythmia as judged by the investigator at the time of screening;
3.
Subjects with prior personal or family history of long-QT syndrome, family history of
sudden death of any immediate family members (meaning a parent, child, or sibling)
prior to the age of 40 years; and/or personal history of unexplained syncope within 1 year
prior to screening; and/or QTcF > 450 ms (male), QTcF > 470 ms (female) measured by
ECG at rest during screening;
4.
Subjects with unstably controlled hypertension at screening, defined as the systolic blood
pressure ≥160 mmHg and/or the diastolic blood pressure ≥100 mmHg (verify before
randomization);
5.
Subjects with symptomatic orthostatic hypotension at screening, or who experiences a
decrease in systolic blood pressure of ≥30 mmHg or a decrease in diastolic blood
pressure of ≥15 mmHg within 3 minutes when changing from the supine to the standing
position (verify before randomization);
6.
Atypical PD (e.g., Parkinsonism, multiple system atrophy, progressive supranuclear
palsy), or secondary PD (e.g., delayed or drug-induced PD);
7.
Subjects who have clinically significant hepatic insufficiency which is defined as the
total bilirubin (TBIL) > 2 × upper limit of normal (ULN) or alanine aminotransferase
(ALT) and/or aspartate aminotransferase (AST) > 2 × ULN;
8.
Subjects who have clinically significant renal insufficiency (creatinine clearance [Ccr] <
30 mL/min, see the calculation formula inAppendix II);
9.
Any condition (e.g., severe arthritis, severe dyskinesia, traumatic injury with permanent
physical disability) that may affect the MDS-UPDRS motor examination;
10. Subjects who have a history of suicidal intention (including actual attempts, interrupted
attempts, or failed attempts) and are at risk of committing suicide as judged by the
investigator;
11. Subjects who suffer from severe mental abnormalities (anxiety, depression) as judged by
the investigator, and the depression or anxiety score as rated by the Part I of the MDS-
UPDRS is ≥3 at screening;
12. Subjects who have taken any serotonin reuptake inhibitors (such as fluoxetine, paroxetine,

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trazodone, citalopram, escitalopram, etc.) within 4 weeks prior to screening;
13. Subjects who have dementia or moderate or above cognitive dysfunction and the MDS-
UPDRS score for 1.1 cognitive impairment is ≥3 at screening;
14. Subjects who have a history of surgical treatment for PD (e.g., deep brain stimulation,
pallidotomy, etc.), or those who have undergone any major or medium surgery or have
experienced any serious trauma or serious infection within 3 months prior to screening,
those who are unsuitable for this study at the discretion of the investigator or plan to
undergo any surgical treatment (excluding an outpatient surgery that has no impact on
subject safety or study results as judged by the investigator) during the study;
15. Subjects who have participated in a clinical trial that involves the administration of an
investigational drug (a new chemical entity), device, or surgery within 3 months or 5
half-lives before screening, whichever is longer;
16. Subjects with evidence of alcoholism (≥14 units of alcohol per week on average, 1 unit ≈
360 mL of beer, 45 mL of liquor, or 150 mL of wine) or drug abuse within 6 months prior
to screening that may interfere with the subject's understanding of the study or
completion of the study as judged by the investigator;
17. Subjects who are known to have hypersensitivity/allergic reaction or intolerance to any
component of the investigational product;
18. Subjects with a history of hepatitis B, or positive for any of the hepatitis B surface
antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus
(HIV) antibody, and Treponema pallidum antibody (TP-Ab) at screening;
19. Pregnant or breastfeeding women;
20. Subjects who are unable to swallow oral drugs, or have any condition that may
significantly affect the absorption, distribution, metabolism and excretion of the drug, or
any condition that may pose a hazard to subjects participating in the study, as judged by
the investigator;
21. Subjects who have a history of organ transplantation (excluding corneal transplantation);
22. Subjects who have donated or lost blood of ≥400 mL, or received blood transfusions
within 3 months prior to screening;
23. Subjects who have any other conditions that may affect study compliance as deemed by
the investigator, or those who are unable to participate in the study for their own reasons.

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4.3 Definition and Handling of Screen Failures
If a subject does not meet the eligibility for this study, it will be considered a screen failure,
and the reasons should be documented in detail in the original medical record.
If screen failure is caused due to abnormal results during the screening process, and if the
investigator judges that there is a clear justification for retesting, and the tests can be repeated
within the time window once, but the reason for repeating the test should be recorded.
Subjects with screening failure are only allowed for re-screening once during the enrollment
stage of this study. Additional medications are not allowed to correct the abnormal values (e.g.
hepatoprotective drugs used to address hepatic function abnormal) prior to the re-
measurement or re-screening. Parameters that are allowed for retesting include: blood
pressure, ECG, creatinine, AST, ALT, and TBIL.
In the event of re-screening, the subject must sign a new ICF, a new subject screening number
will be assigned, and all sample collection and assessment will be performed again.
4.4 Criteria for Early Withdrawal from the Trial
Subjects may voluntarily request for study withdrawal at any time, or may be withdrawn from
the study at any time at the request of the investigator or the sponsor for safety, behavioral or
administrative reasons.
Withdrawal at the subject's discretion
If the subjects are unwilling to continue the clinical trial, they have the right to withdraw their
consent and withdraw from the study at any stage.
Withdrawal at the investigator's discretion
It refers to the condition during the study in which the investigator finds that an enrolled
subject is no longer suitable for the participation in the study and decides that the subject
should be withdrawn from the study. These conditions include, but are not limited to:

Continuing the study may affect the safety of the subject and be unfavorable to the
subject at the discretion of the investigator based on the following clinical
considerations:
-
QTcF >500 ms at rest (after resting for at least 5 minutes; the average of two
measurements taken within 20 minutes) or an increase of >60 ms from baseline;
-
Discontinuation of study treatment due to hepatic event or hepatic function
abnormal:

ALT or AST>8×ULN; or

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
ALT or AST>5×ULN for over 2 weeks; or

ALT or AST>3×ULN and (TBIL>2×ULN or International Normalized Ratio
[INR]>1.5); or

ALT or AST>3×ULN, with fatigue, nausea, vomiting, right upper quadrant
pain or tenderness, pyrexia, rash, or eosinophilia (> 5%).
-
Occurrence of other intolerable AEs which requires treatment discontinuation as
judged by the investigator;

Any major protocol deviations (such as subjects who fail to meet the inclusion
criteria have been mistakenly included in the study) or protocol violations, which
may have a significant impact on the evaluation of the efficacy and safety of the drug;

Subjects have poor compliance that affects efficacy and safety assessment;

Female subjects are pregnant;

Subjects are lost to follow-up;

Subjects have participated in other clinical trials (which is defined as having signed
the ICF of any other study) during the study;

Subjects have been unblinded due to various reasons;

Other circumstances in which the subject needs to be withdrawn from the trial at the
discretion of the investigator.
Handling of Subjects Early Withdrawn
Subjects who have early withdrawn from the study should complete the early withdrawal visit
(if it is less than 7 days from the date of the previous visit, repeated tests of the same item can
be waived) within 7 days after the investigator's awareness, unless they voluntarily decide to
withdraw from the study and refuse to have early withdrawal visit.
For subjects who withdraw from the study due to an AE or SAE, the investigator should take
appropriate treatment measures according to the actual situation of the subjects, and closely
follow up their condition until the AE or SAE is clinically recovered, stabilized, returns to
screening or baseline level (if baseline level is known), the subject is lost to follow-up (e.g.,
no more information is available or the subject/caregiver refuses to provide any information),
or dead, which will be recorded in the original data.
For all the subjects who have early withdrawn from the study, their study medical records
should be retained and recorded in the electronic case report form (eCRF), and the EOT page
and the reason for failure in completing the study should be filled out.

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4.5 Criteria for Study Termination/Site Closure
The sponsor has the right to terminate the study at any time, and the sponsor and the
investigator have the right to close the study site at any time. However, such a procedure can
be implemented only after mutual agreement. When the study is terminated, it must be
reported to the Independent Ethics Committee (IEC) and Institutional Review Board (IRB).
Upon early termination of study or early closure of study site, all study materials (except
those documents that must be retained at the site) must be returned to the sponsor. The
investigator must retain other documents until notified by the sponsor of their destruction.
Reasons for the early termination of the study or the closure of the study site include but are
not limited to:

The study is required to be terminated due to significant AEs occurred in the study
for safety reasons;

An event that seriously violates the clinical study protocol, Good Clinical Practice
(GCP) or relevant regulatory requirements occurs during the study, requiring
termination of the study;

The sponsor requests termination under the premise of fully protecting the rights and
interests, and safety of subjects (e.g., funding reasons, management reasons, efficacy
reasons, etc.);

National Medical Products Administration (NMPA) or the Ethics Committee orders
the termination of the trial for some reason.

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5 Overall Trial Design
5.1 Trial Design
5.1.1 Overall Design
This study is a randomized, double-blind, placebo parallel-controlled phase II clinical trial
which is designed to assess the efficacy and safety of TJ0113 capsules in the treatment of
patients with early-stage PD. It is planned to include approximately 150 subjects with early-
stage PD who will be randomized in a 1:1 ratio into two cohorts (Cohort 1: 200 mg dose
group; Cohort 2: 400 mg dose group). Within each cohort, subjects who have been
successfully screened will be randomly assigned to TJ0113 capsules group and the placebo
group in a ratio of 2:1 within each stratum based on a stratification factor whether they have
been receiving levodopa, the background medication for PD (yes vs. no) at a stable dose.
Among them, approximately 50 subjects will receive TJ0113 capsules and approximately 25
subjects will receive the placebo. In this study, there will be approximately 50 subjects in each
of the TJ0113 capsules 200 mg group, TJ0113 capsules 400 mg group and the placebo group.
After randomization, subjects will receive the oral administration of TJ0113 capsules or the
placebo for 12 consecutive weeks and continue to receive follow-up visits for 1 week
(telephone follow-up) after the end of treatment. For subjects who have been receiving the
anti-PD drug at a stable dose for at least 4 weeks prior to study entry, the original regimen of
the background medication for PD should be maintained during the study.
5.1.2 Trial Period
This trial consists of a screening period, a treatment period and a follow-up period.
Screening period (up to 4 weeks)
At screening, the subject will be assigned a “screening number” for ID identification after
signing the informed consent form. The day of first dose for subjects screened successfully is
taken as Day 1 (D1) of the trial (for other days, by this rule); and subjects are screened within
28 to 2 days before the start of the trial, and the required eligible subjects are screened. The
scale scores, demographic data, medical history, medication history, physical examinations,
height and weight, vital signs and laboratory tests of the subjects before the trial are recorded.
Treatment period (12 weeks)
Subjects who have been successfully screened will receive oral administration of the drugs as
required on D1, once daily for 12 weeks.
Follow-up period (1 week, telephone follow-up)

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Follow-up will be continued for 1 week after the end of the treatment period, and AE and
concomitant medication information will be collected via telephone follow-up. If an AE/SAE
occurs during the study, it will be followed up by the investigator until it has been clinically
recovered, stabilized, returns to the screening or baseline level (if baseline level is known), the
subject is lost to follow-up (e.g., no more information is available or the subject/caregiver
refuses to provide any information), or dead.
5.2 Justification for Design (Population, Dose, etc.)
5.2.1 Justification for Overall Study Design
This is a randomized, double-blind, placebo parallel-controlled phase II clinical trial, which is
planned to enroll 150 PD subjects. Subjects who are successfully screened will be randomized,
and the efficacy will be evaluated after oral administration for 12 consecutive weeks and
subjects will continue to be followed up for 1 week after the end of treatment. Male or female
subjects aged between 30 and 80 years (both inclusive) will be included in this study,
including elderly subjects. Based on the PK model, the PK profile of TJ0113 following the
oral administration at doses of 80 mg, 160 mg, and 400 mg in the elderly population (65, 70,
and 80 years) is speculated to be similar to that of adult subjects.
5.2.2 Justification for Dose
The proposed doses of TJ0113 capsules for this study are 200 mg QD and 400 mg QD. The
dose design is primarily based on the results of non-clinical pharmacology studies of TJ0113
and the currently completed phase I study.
The PD studies of compound TJ0113 in the MPTP-induced mouse PD model and the study of
the mitochondrial repair effect of compound TJ0113 in the MPTP-induced mouse PD model
indicated that TJ0113 has different degrees of therapeutic effect on PD model within the dose
range of 10, 30, and 60 mg/kg once daily. Based on this data, the human equivalent dose
(HED) calculated by the body surface area normalization method was 0.9, 2.7, and 5.4 mg/kg,
respectively and 54, 162, and 324 mg based on an adult body weight of 60 kg.
The PD study of TJ0113 in the 6-OHDA-induced rat PD model suggested that TJ0113 had
different degrees of therapeutic effect on the PD model at doses of 5, 15, and 30 mg/kg once
daily. Based on this data, the HED calculated by the body surface area normalization method
was 0.8, 2.5, and 4.9 mg/kg, respectively, and 48, 150, and 294 mg based on an adult weight
of 60 kg.
In the kinetics study in the plasma of rats (TJ22039PKAB18), the results of the mean plasma
PK parameters of the unchanged drug after single oral gavage administration to SD rats

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showed that the AUC0-24h was 10.7 ± 4.44 h·μg/mL in the 10 mg/kg dose group and 22.1 ±
6.66 h·μg/mL in the 30 mg/kg dose group. The results of phase I clinical trial of TJ0113 were
as follows: the AUC0-last of the SAD study was 8,570.86 ± 2,413.178 h·ng/mL in the 260 mg
dose group and 12,785.99 ± 4,491.670 h·ng/mL in the 400 mg dose group. Combined with the
PD study of the 6-OHDA-induced rat PD model, both the 200 mg and 400 mg dose levels are
expected to be within the clinically effective dose range.
In addition, data from the phase I study of TJ0113 showed that following the single dose
administration within the dose range of 80-720 mg, and the multiple dose administration at
200 mg QD, 400 mg QD, and 300 mg BID, the safety profiles of TJ0113 capsules were
favorable and the incidence of AEs were similar between the treatment group and the placebo
group. Within the dose range of 80-400 mg, the exposures (AUC0-last and AUC0-inf) increased
in a linear fashion. After 200 mg QD administration, TJ0113 basically did not accumulate in
vivo; after 400 mg QD administration, there was a slight accumulation of TJ0113 in vivo.
In summary, combined with the current strength (100 mg) and clinical compliance of TJ0113
capsules, the proposed doses for this study are 200 mg QD and 400 mg QD.
5.3 Randomization and Blinding
5.3.1 Randomization
After subjects enter the screening period, the screening numbers will be assigned strictly
according to the sequence of study entry. The screening numbers will be expressed by five
Arabic numerals, the first two digits are the site number, and the last three digits are the
screening sequence number. For example, the screening number for the first subject in Site 01
is 01001. Once the subject is assigned with a number, the number cannot be reused.
Subject randomization numbers and drug randomization numbers are compiled by project-
independent randomization statisticians from the Statistics Department. The randomization
statistician generates a subject randomization list and a drug randomization list using the SAS
9.4 or later PLAN process. It is planned to include approximately 150 subjects who will be
randomized in a 1:1 ratio into two cohorts (Cohort 1: 200 mg dose group; Cohort 2: 400 mg
dose group). Within each cohort, subjects who have been successfully screened will be
randomly assigned to TJ0113 capsules group and the placebo group in a ratio of 2:1 within
each stratum based on a stratification factor whether they have been receiving levodopa, the
background medication for PD (yes vs. no) at a stable dose. Among them, approximately 50
subjects will receive TJ0113 capsules and approximately 25 subjects will receive the placebo.
The subject randomization list and drug randomization list will be imported into the

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Interactive Web Response System (IWRS) by the system director. For subjects who have been
successfully screened, the randomization number of the subjects will be obtained by the
investigator through the IWRS, and the subjects will enter the corresponding group according
to the randomization number. Subjects who withdraw from the study midway will not be
allowed to re-enter the study. The specific randomization procedure will be described in the
randomization protocol.
5.3.2 Blinding
The blinding of this study is completed under the guidance of a randomized statistician
independent of the statistical analysis of this project, and the electronic blind code will be kept
by the randomized statistician in a folder with permission control.
During the treatment period, in order to maintain the double-blind status of the study, the
packages for investigational drug and placebo will be identical in physical appearance. The
sponsor, investigators and other personnel involved in the assessment of subjects and
implementation of the trial will not be aware of the distribution of therapeutic drugs.
Throughout the study, all personnel involved in blinding should remain blinded until the
database is locked.
5.3.2.1 Blinding Implementation
The placebo has the same dosage form, appearance, strength, color, weight, smell and taste as
the investigational drug, and does not contain any active ingredients. The packages for
investigational drug and placebo will be identical in physical appearance to ensure the
implementation of the blinding method. The sponsor or its designee will assign a blind code
to the investigational drug and placebo.
Subjects who meet all inclusion criteria and none of the exclusion criteria will be randomized.
For subjects who require to be randomized and dispensed with drug, the information of
randomization number, randomization time, drug number and drug dispensing time are all
provided by the Clinflash drug dispensing system. The investigator or his/her designee will
log in to the Clinflash IRT system, obtain the information of the randomization number and
the corresponding drug number, and distribute the corresponding investigational product
according to the drug number.
5.3.2.2 Unblinding Provisions
The database will be locked when all eCRF data are entered and signed as well as reviewed in
a blinded manner, the analysis population is determined, and the statistical analysis plan (SAP)

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is signed. After the database is locked, unblinding is carried out to determine the subject
group, and the unblinding record is kept. The unblinding must be signed and confirmed by the
sponsor and the statistician.
5.3.2.3 Emergency Unblinding
Emergency unblinding refers to obtaining the treatment grouping information of individual or
some subjects in emergency through pre-established standard operating procedures based on
the safety considerations of subjects and other special reasons in accordance with the clinical
trial protocol. It should only be performed if the investigator must know the treatment
grouping information of the subject who experiences an emergency (e.g., when the subject
experiences an SAE or is in urgent need of rescue treatment). There is no need for emergency
unblinding, if it is known that the treatment grouping information is not necessary for
management of the emergency.
In the event of emergency unblinding, it is necessary to timely record the time, reason and
operator of emergency unblinding, notify the CRA as soon as possible, and submit the safety
event report to the Ethics Committee. Upon emergency unblinding, the subject must terminate
the treatment. The investigator should record the reason for termination of treatment in the
case report form.
In addition, if an unexpected serious adverse event occurs, the Pharmacovigilance Department
should also unblind the individual subjects according to the corresponding procedures.
5.4 Definition of End-of-Study (EOS)
The end of the study (EOS) is when the last subject has his/her last study visit, unless the EOS
is caused by a condition described in Section 4.5 (Criteria for Study Termination/Site Closure).
The EOS for an individual subject is defined as when the subject completes V7 or is early
withdrawn from the study (see Section 4.4 for criteria for early withdrawal). For subjects who
early withdraw from the study, the date on which the last visit is completed or the last contact
is made is the date of EOS (whichever occurs later).
5.5 Definition and Handling of Loss to Follow-up
If the investigator fails to contact the subject through multiple attempts of various methods (at
least 3 telephone calls and 1 SMS/WeChat, and each attempt is not on the same day), the
subject can be judged as lost to follow-up, and the corresponding contact records (contact
person, contact information and specific time) should be maintained, and the date of the last
contact should be considered as the date of the subject's early withdrawal.

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6 Study Treatment
6.1 Investigational Products
In this study, the investigational products include the investigational drug (TJ0113 capsules)
and the placebo.
TJ0113 Capsules
Placebo
Active
Ingredient
TJ0113
None
Dosage Form
Capsules
Capsules
Strength
100 mg
100 mg
Package Size
30 capsules/bottle
30 capsules/bottle
Description
Opaque rich yellow hard
capsules, and with pale pink
solid contents
Opaque rich yellow hard capsules,
and with off-white solid contents
Storage
Conditions
Protected from light, keep in
tight container at 2℃- 8℃
Protected from light, keep in tight
container at 2℃- 8℃
Provided by
Hangzhou PhecdaMed Co., Ltd.
Method of
Administration
Take orally on an empty stomach in the morning, once daily, and
fast within half an hour after the administration. It can be taken
together with the background medication for PD. It is recommended
that subjects should take the drug at the same time ± 1 h each day as
much as possible.
6.2 Drug Storage
Both the investigational drug and the placebo will be provided free of charge by Hangzhou
PhecdaMed Co., Ltd. and distributed to the study site as scheduled. The investigational drug
should be kept and distributed by specially-assigned person in the clinical trial institution, and
stored in a refrigerator at 2-8℃as required. Returned drugs (used, partially used or unused
drugs, including empty packaging materials) must be kept separately from the drugs that are
not dispensed.
6.3 Drug Dispensing
All investigational products will be randomized by the IWRS, and each subject will be
assigned multiple drug numbers by visit during the study. The system will automatically
record the drug allocation information of each subject, including the date of drug dispensing
and drug number. The drug manager should dispense the drugs according to the drug number

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assigned by the system at each visit.
6.4 Drug Receipt, Record and Accountability
The drugs will be administered at each site by the principal investigator or his or her
authorized representative (e.g., pharmacist), i.e., the drug manager. The third-party
transportation company designated by the sponsor will transport the drugs to each study site
according to the transportation requirements of the drug. The drug manager will receive the
drug after confirming that the packaging of the drug is intact and there is no temperature
excursion, and ensure that all investigational drugs are safely stored according to relevant
regulations and drug storage requirements. The quantity of received drugs, the date of receipt,
the quantity used, the date of use, and the storage amounts will be recorded and counted
accordingly, and the CRA should check and conduct accountability at each visit.
6.5 Drug Return and Destruction
All drugs will be returned by the investigator after the EOS or returned to the third-party drug
destruction company designated by the sponsor in batches according to the actual situation of
the site during the study. The company will carry out uniform destruction according to the
corresponding regulations and requirements.

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7 Treatment for Study Participants
7.1 Study Treatment
Subjects enrolled in this study will be randomized in a 1:1 ratio into two cohorts (Cohort 1:
200 mg dose group; Cohort 2: 400 mg dose group) based on a stratification factor whether
they have been receiving levodopa, the background medication for PD (yes vs. no) at a stable
dose. Within each cohort, the subjects will be randomized into the TJ0113 capsules group and
the placebo group in a ratio of 2:1.
7.2 Concomitant Medication
All concomitant medications used during the study must be documented with indication and
dose information (including dose, route of administration and dosing frequency), and start and
stop dates of administration. Medications used prior to signing the ICF will be recorded as
prior medications, and those used after signing the ICF will be recorded as concomitant
medications. All concomitant medications should be documented in the subject's original
medical record and the eCRF.
7.2.1 Permitted Concomitant Medications/Therapies
Concomitant medications/therapies allowed to be administered from signing of the ICF to 1
week after the last dose of the investigational product include:

Background medications for PD that have been stably used for at least 4 weeks
before study entry, of which the treatment regimen can remain unchanged (for
subjects who have used any background medications for PD including levodopa, if
any AE such as dyskinesia occur, the dose of levodopa is allowed to be reduced at
the discretion of the investigator);

Other concomitant medication or therapies that have already been used at the time
of screening, of which the original drug/therapy type, dose or treatment frequency
and setting should remain unchanged as much as possible;

Drugs required to be used for treating the AEs.
7.2.2 Prohibited Concomitant Medications/Therapies
The following medications/therapies are prohibited during the period from signing the ICF
until 1 week after the last dose of the investigational product:

Any procedure/surgery that may affect the progression of PD, including but not

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limited to brain surgery (such as stereotactic destruction and deep brain stimulation)
or traditional Chinese medicine physiotherapy (such as acupuncture), etc.;

Any drugs other than investigational product that may affect the progression of PD
(excluding those which have been on a stable dose for PD at the time of study entry).

Serotonin reuptake inhibitors (such as fluoxetine, paroxetine, trazodone, citalopram,
escitalopram, etc.);

Any unauthorized drugs (i.e., other investigational drugs that are currently tested in
clinical trials and have not been approved for marketing).
The investigator will determine and record the use of any emergency medication, drug name,
dose, route of administration, purpose of treatment, start and end date of administration.
If subjects have used any prohibited drug or non-drug therapy, it will be recorded as a
protocol deviation. The investigator decides on whether the subjects will continue the follow-
up or be withdrawn from the study based on the severity of the deviation and the subjects’
condition
7.3 Compliance of Study Subjects
During the study, the administration of both the investigational product and the background
medication for PD will be recorded in the eCRF. Subjects' medication compliance will be
calculated according to the quantity of investigational product dispensed and returned and
combined with the diary card.
Calculation method for medication compliance: medication compliance = actual dose/planned
dose * 100%.
If the subject's compliance is between 80% and 120%, it means that the compliance is good; if
the subject's compliance is < 80% or > 120%, it indicates poor compliance.

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8 Endpoint-Related Assessment
8.1 Efficacy Assessment
8.1.1 MDS-UPDRS
The MDS-UPDRS consists of four parts: Part I (Nonmotor Experiences of Daily Living), Part
II (Motor Experiences of Daily Living), Part III (Motor Examination), and Part IV (Motor
Complications). Throughout the study, each subject should have a fixed rater to evaluate
his/her score using MDS-UPDRS.

For subjects who have received the anti-PD drug at a stable dose for at least 4 weeks
prior to study entry, the MDS-UPDRS assessment time points and corresponding
assessment parts are as follows:
Visit
MDS-UPDRS
assessment part
Assessment time points
V1
Part I
No special requirements
Part III
Before administration of background medication for
PD (≥12 hours from the most recent dose of the
background medication for PD)
V2, Early
Withdrawal
Visit (if
applicable)
Part III
Before administration of background medication for PD
(≥12 hours from the most recent dose of the background
medication for PD)
After administration of background medication for PD
(to be performed at 2 ± 1 hours after the administration
of background medication for PD at this visit)
Parts I, II, and
IV
No special requirements
V3~V6
Part III
Before administration of the investigational product and
the background medication for PD (≥12 hours from the
most recent administration of background medication for
PD and the investigational product)
After administration of the investigational product and
the background medication for PD (to be performed at 2
± 1 hours after the administration of the background
medication for PD and the investigational product at this
visit)
Parts I, II, and
IV
No special requirements

For subjects who have not received the anti-PD drug at study entry, the MDS-UPDRS
assessment time points and corresponding assessment parts are as follows:

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Visit
MDS-UPDRS
assessment part
Assessment time points
V1
Part I
No special requirements
Part III
No special requirements
V2
Part III
No special requirements
Parts I, II, and IV
No special requirements
V3～V6
Part III
Before administration of the investigational product (≥12
hours from the most recent administration of the
investigational product)
After administration of the investigational product (to be
performed at 2 ± 1 hours after the administration of the
investigational product at this visit)
Parts I, II, and IV
No special requirements
Early
Withdrawal
Visit (if
applicable)
Part III
≥12 hours from the most recent administration of the
investigational product
Parts I, II, and IV
No special requirements
8.2 Safety Assessment
8.2.1 Vital Signs
They include respiration, pulse, body temperature, and blood pressure. Among them, blood
pressure measurement on the day of V1 and before randomization at V2 should be measured
after the subject has rested in a supine position for at least 5 min. After the supine blood
pressure measurement is completed, let the patient stand upright and complete the
measurement of standing blood pressure within 3 min in a standing resting state; for other
vital signs measurements, it can be measured with the subject in a sitting position after having
rested for at least 5 min.
Vital signs will be measured at all site visits in this study.
8.2.2 Physical Examination
It includes skin and mucous membranes, lymph nodes, head, neck, chest, abdomen, spine and
limbs, nervous system and mental state.
Physical examination will be performed at all site visits in this study.
8.2.3 12-lead ECG
It should be performed with the subject in a supine position after having rested for at least 5
min. Two measurements will be taken within 20 minutes, and the average value is calculated

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and rounded to the nearest integer.
The parameters include: heart rate, PR interval, QRS complex duration, uncorrected QT
interval, and Fridericia-corrected QTc (QTcF).
12-lead ECG will be performed at all site visits in this study. If a 12-lead ECG has been
performed within 7 days (exclusive) prior to V2, it is not necessary to repeat this examination
at V2; otherwise, it should be re-examined at V2 and confirm the eligibility for study entry
based on the examination results.
8.2.4 Laboratory Tests
They include hematology, blood chemistry, urinalysis, coagulation function, serum pregnancy
test, urine pregnancy test, etc. Each test item includes:

Hematology:
white blood cell count, absolute neutrophil count,
neutrophil
percentage, absolute lymphocyte count, lymphocyte percentage, absolute monocyte
count, monocyte percentage, absolute eosinophil count, eosinophil percentage,
absolute basophil count, basophil percentage, red blood cell count, hemoglobin,
hematocrit, mean corpuscular volume, mean corpuscular hemoglobin content, mean
corpuscular hemoglobin concentration, red blood cell distribution width, platelet
count, mean platelet volume, platelet hematocrit, and platelet distribution width;

Blood chemistry: fasting blood glucose, bile acid, total protein, albumin, globulin,
albumin/globulin ratio, TBIL, direct bilirubin, indirect bilirubin, ALT, AST, gamma-
glutamyltransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase,
creatine kinase isoenzyme MB, urea/blood urea nitrogen, blood uric acid, creatinine,
potassium,
sodium,
chloride,
calcium,
magnesium,
inorganic
phosphorus,
triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density
lipoprotein cholesterol;

Urinalysis: urine glucose, urine bilirubin, urine ketone body, urine pH, urine protein,
urobilinogen, urine nitrite, urinary occult blood, urine white blood cells, urine red
blood cells, urinary sediment microscopic examination (red blood cells, white blood
cells) and urine specific;

Coagulation
function
test:
including
prothrombin
time,
activated
partial
thromboplastin time, thrombin time, international normalized ratio and fibrinogen;

Serum pregnancy test: female subjects of childbearing potential will receive serum

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pregnancy test at screening;

Urine pregnancy test: female subjects of childbearing potential will receive urine
pregnancy test from V2 to V6 and other visits specified in the protocol. If the urine
pregnancy test result is positive, serum pregnancy test must be performed for
confirmation.
Hematology, blood chemistry, urinalysis, and coagulation tests are performed at all on-site
visits in this study; creatinine clearance (Ccr) is calculated at visits V1, V2, V3, V6, and the
early termination visit (if applicable) based on body weight measurements and serum
creatinine levels from the blood chemistry tests, with the calculation formula provided in
Appendix II. (If body weight was measured during demographic data collection at V1,
remeasurement is not required during that visit.) If hematology, blood chemistry, coagulation
function test, urinalysis body weight measurement and Ccr calculation have been performed
within 7 days (exclusive) before V2, these tests are not required to be repeated on V2;
otherwise, they are required to be re-tested at V2 and the eligibility for the study enrollment
should be confirmed according to the test results.
Although the screening for infectious diseases also requires laboratory tests, it is not a
relevant parameter for the evaluation of the endpoint of this study. It should only be tested
during the screening period; therefore, it is not listed in this section. Screening for infectious
diseases is detailed in Section 8.4.
Laboratory tests that require subjects to be fasted are provided in Section 8.5.
If certain items are not included in routine tests at some study sites, they can be tested
separately.
Information on sample collection, processing, preservation and destruction should comply
with the regulations of the laboratory of the study site.
8.3 Evaluation of Exploratory Indicators
8.3.1 Exploratory Inflammatory Indicators
The exploratory inflammatory indicators of this study include interleukin (IL)-1β, IL-2, IL-4,
IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ, and tumor necrosis
factor (TNF)-α; the specific indicators to be tested are subject to the actual implementation at

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each center.
The design of blood sampling points for exploratory inflammatory indicators is as follows:

V2, V4, V5, V6;

Early withdrawal visit (if applicable).
8.3.2 Exploratory PD Biomarkers
The exploratory PD indicators of this study include α-synuclein and GFAP. Blood samples
will be collected at V2, V6, and Early Discontinuation/Early Withdrawal Visit (if applicable),
with a total of 5 mL of blood collected per visit, and sent to the central laboratory for testing.
All other test samples in this trial will be tested in local laboratories.
8.3.3 Exploratory Skeletal Muscle Mass and Function Assessment
The exploratory skeletal muscle mass and function assessment indicators of this study include
ASMI, muscle strength (grip strength) and 6-meter walking speed test (the specific indicators
to be tested are subject to the actual operation at each center), all of which will be assessed at
V2, V6, and early withdrawal visit (if applicable). Among them, ASMI is detected and
calculated by dual-energy X-ray absorptiometry (DXA), and the calculation formula is ASMI
= appendicular muscle mass (kg) / height2 (m2). If the V2 visit is not assessed, then the V6
and early withdrawal visits should also not be assessed.
8.3.4 Exploratory Genomic Resequencing
To explore the association between the efficacy of TJ0113 capsules and the genomic
characteristics in patients with early-stage PD, this study will collect blood samples from
subjects for genomic resequencing. Each subject will be collected once at V2 (if not collected
at V2, it is allowed to be supplemented at V6 or early withdrawal visit).
8.4 Tests/Assessments Required for V1 during Screening Period Only
Tests/assessments required for V1 only include:

Screening for infectious diseases: including hepatitis B five-item panel (HBsAg,
hepatitis B virus surface antibody, hepatitis B virus e antigen, hepatitis B virus e
antibody, hepatitis B virus core antibody), HCV antibody, HIV antibody, and
Treponema pallidum antibody detection. If certain items are not included in routine
tests at some study sites, they can be tested separately.

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
B-ultrasound: detection sites include liver, gallbladder, pancreas, spleen, and kidney.

Tumor marker detection: including alpha-fetoprotein (AFP), carcinoembryonic
antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125
(CA125) (only for females), total prostate specific antigen (T-PSA) (only for males),
free prostate specific antigen (F-PSA) (only for males), carbohydrate antigen 153
(CA153), squamous cell carcinoma antigen (SCC), ferritin.

Test of serum follicle stimulating hormone: this test is performed at screening only
in women whose menopause occurred within the last 24 months or who are
uncertain about their menopausal status.

Assessment using modified Hoehn and Yahr Scale.
8.5 Parameters to be Tested Under a Fasted State
Subjects must be fasted before each visit (fast for at least 10 hours overnight without
depriving of water). It is recommended that fasting blood samples be collected between 7:00
a.m. and 10:00 a.m., and the specific collection time point is subject to the implementation of
each study site. The investigational product or background medication for PD should not be
administered prior to blood collection. If the subject has not fasted before the visit, an
additional fasting collection should be scheduled.
Parameters to be tested under a fasted state at site visit include: hematology, blood chemistry,
B-ultrasound, and exploratory inflammatory indicators; there is no fasting requirement for
other parameters at site visit.
8.6 Sample Submission Plan
Blood samples (total 5 mL) for exploratory analysis of α-synuclein and GFAP indicators need
to be sent to the central laboratory for testing after collection. Blood samples (total 5 mL) for
exploratory analysis of genomic resequencing need to be sent to the central laboratory for
testing after collection. All other test samples in this trial will be tested in local laboratories.
8.7 Trial Procedure
The study consists of a screening period, a treatment period and a follow-up period. After
subjects sign the written ICF, they will receive all the tests and trial procedures according to
the study requirements.

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Before V1, the investigator should inform the subject in advance that the last dose of the
background medication for PD on the day before V1 should be at least 12 hours apart from
the agreed visit time of V1, and the subject should bring background medication for PD (at
least a single dose) that has been stably taken to the hospital on the day of V1, and take the
first dose of such medication on the day of V1 under the guidance of the investigator.
Collection of blood samples for exploratory analysis of genomic resequencing: each subject
will be collected once at V2 (if not collected at V2, it is allowed to be supplemented at V6 or
early withdrawal visit).
8.7.1 Screening Period
8.7.1.1 V1 (D-28-D-2, W-4-W-1)
At V1, the following procedures will be performed:

Sign an ICF;

Subjects must be fasted before each visit (fast for at least 10 hours overnight without
depriving of water).

Collect demographics: including date of birth, age, gender, ethnicity, height, weight,
and BIM, etc.;

Collect the history of diagnosis and treatment of PD;

Collect other medical history and treatment history: including other past and current
medical history (excluding PD), treatment history, surgical history and surgical plan,
etc.;

Collect other personal history: including but not limited to family history, allergy
history, alcohol consumption history, substance abuse history, blood transfusion
history, and childbearing plan, etc.;

Vital signs: blood pressure measurement should be performed after the subject has
rested in a supine position for at least 5 min; after supine blood pressure
measurement is completed, have the patient stand upright and measure standing
blood pressure within 3 min while resting in an upright position; other vital signs
can be measured with the subject in a sitting position after having rested for at least

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5 min;

Physical examination;

12-lead ECG;

Laboratory tests: including hematology, blood chemistry, urinalysis, coagulation
function, screening for infectious diseases, serum pregnancy test (only for women of
childbearing potential), serum follicle stimulating hormone test (only for women
whose menopause occurred within the last 24 months or who are uncertain about
their menopausal status);

Weight measurement and Ccr calculation (If weight has been measured when
collecting demographics at V1, it is not necessary to repeat the weight measurement
during that visit);

B-ultrasound: detection sites include liver, gallbladder, pancreas, spleen, and kidney;

Tumor marker detections: including AFP, CEA, CA199, CA125 (only for females),
T-PSA (only for males), F-PSA (only for males), CA153, SCC, ferritin;

Assessment using modified Hoehn and Yahr Scale;

MDS-UPDRS Part I and III scores (if the subject has received stable medication for
PD within at least 4 weeks prior to study entry, Part III score must be ≥12 hours
from the most recent dose of background medication for PD);

Use background medication for PD (if applicable);

Record concomitant medications/therapies;

Record AEs;

Assess against inclusion/exclusion criteria;

Note:
-
At V2, subjects who are eligible after screening should return to the study site
in the morning (recommended from 7:00 am to 10:00 am) for a site visit;
-
If the subject has received stable medication for PD within at least 4 weeks
prior to study entry, the last dose of the background medication for PD on the
day before V2 should be at least 12 hours apart from the agreed visit time of V2,
and the subject should bring background medication for PD (at least a single

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dose) that has been stably taken to the hospital on the day of V2, and take the
first dose of such medication on the day of V2 under the guidance of the
investigator.
If screen failure is caused due to abnormal results during the screening process, and if the
investigator judges that there is a clear justification for retesting, and the tests can be repeated
within the time window once, but the reason for repeating the test should be recorded.
Subjects with screening failure are only allowed for re-screening once during the enrollment
stage of this study. Additional medications are not allowed to correct the abnormal values (e.g.
hepatoprotective drugs used to address hepatic function abnormal) prior to the re-
measurement or re-screening. Parameters that are allowed for retesting include: blood
pressure, ECG, creatinine, AST, ALT, and TBIL.
8.7.1.2 V2 (D-1, W-1)
At V2, the following procedures will be performed:

Subjects must be fasted before each visit (fast for at least 10 hours overnight without
depriving of water);

Vital signs: blood pressure measurement should be performed after the subject has
rested in a supine position for at least 5 min; after supine blood pressure
measurement is completed, have the patient stand upright and measure standing
blood pressure within 3 min while resting in an upright position; other vital signs can
be measured with the subject in a sitting position after having rested for at least 5
min;

Physical examination;

12-lead ECG;

Laboratory tests: including hematology, blood chemistry, urinalysis, coagulation
function test, and urine pregnancy test (only for women of childbearing potential);

Weight measurement and Ccr calculation;

Assess against inclusion/exclusion criteria;

Randomization;

Collect blood samples for exploratory analysis (one blood sample each for
inflammatory indicators and PD biomarkers; among these, 5 mL of blood is

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collected for PD biomarker testing and sent to the central laboratory for testing);

Exploratory skeletal muscle mass and function assessment: including ASMI, muscle
strength (grip strength) and 6-meter walking speed test (specific test indicators are
subject to the actual operation of each center). Among them, ASMI is detected and
calculated by DXA, and the calculation formula is ASMI = appendicular muscle
mass (kg) / height2 (m2);

MDS-UPDRS Part III score before the administration of background medication for
PD (only applicable to subject who has received stable medication for PD within at
least 4 weeks prior to study entry, and this score should be ≥12 hours from the most
recent dose of background medication for PD);

Dispense the drug using the Clinflash IRT system;

Take background medication for PD (only applicable to subject who has received
stable medication for PD within at least 4 weeks prior to study entry);

MDS-UPDRS score: Parts I, II, III, IV (if the subject has received stable medication
for PD within at least 4 weeks prior to study entry, Part III score must be assessed at
2 ± 1 hours after the administration of background medication for PD at this visit);

Record concomitant medications/therapies;

Record AEs;

Dispense and instruct subjects to complete diary cards;

Note:
-
At V3, subjects should return to the study site for a visit in the morning
(recommended from 7:00 a.m. to 10:00 a.m.) with their diary cards and on an
empty stomach (fast for at least 10 hours overnight without depriving of water);
-
If the subject has received stable medication for PD within at least 4 weeks
prior to study entry, the administration of investigational product and last dose
of the background medication for PD on the day before V3 should be at least 12
hours apart from the agreed visit time of V3, and the subject should bring
background medication for PD (at least a single dose) that has been stably taken
to the hospital on the day of V3, and take the first dose of such medication on
the day of V3 under the guidance of the investigator.

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If hematology, blood chemistry, coagulation function test, urinalysis, 12-lead ECG
examinations, weight measurement and Ccr calculation have been performed within 7 days
(exclusive) before V2, these tests are not required to be repeated on V2; otherwise, they are
required to be re-tested at V2 and the eligibility for the study enrollment should be confirmed
according to the test results.
8.7.2 Treatment Period
8.7.2.1 V3 (D7, W1)
At V3, the following procedures will be performed:

Subjects must be fasted before each visit (fast for at least 10 hours overnight without
depriving of water);

Vital signs;

Physical examination;

12-lead ECG;

Laboratory tests: including hematology, blood chemistry, urinalysis, coagulation
function test, and urine pregnancy test (only for women of childbearing potential);

Weight measurement and Ccr calculation;

Return diary card;

MDS-UPDRS Part III score before administration of the investigational product and
the background medication for PD (if applicable) (≥12 hours from the most recent
administration
of
background
medication
for
PD
(if
applicable)
and
the
investigational product);

Dispense the drug using the Clinflash IRT system;

Take investigational product and background medication for PD (if applicable)
concomitantly;

MDS-UPDRS Part III score after administration of the investigational product and
the background medication for PD (if applicable) (to be performed at 2 ± 1 hours
after the administration);

MDS-UPDRS Parts I, II, and IV scores;

Record concomitant medications/therapies;

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
Record AEs;

Dispense a new diary card;

Note:
-
At V4, subjects should return to the study site for a visit in the morning
(recommended from 7:00 a.m. to 10:00 a.m.) with their diary cards and on an
empty stomach (fast for at least 10 hours overnight without depriving of water);
-
If the subject has received stable medication for PD within at least 4 weeks
prior to study entry, the administration of investigational product and last dose
of the background medication for PD on the day before V4 should be at least 12
hours apart from the agreed visit time of V4, and the subject should bring
background medication for PD (at least a single dose) that has been stably taken
to the hospital on the day of V4, and take the first dose of such medication on
the day of V4 under the guidance of the investigator.
8.7.2.2 V4 (D28, W4), V5 (D56, W8)
At V4 and V5, the following procedures will be performed:

Subjects must be fasted before each visit (fast for at least 10 hours overnight without
depriving of water);

Vital signs;

Physical examination;

12-lead ECG;

Laboratory tests: including hematology, blood chemistry, urinalysis, coagulation
function test, and urine pregnancy test (only for women of childbearing potential);

Collect blood samples for exploratory analysis (inflammatory indicators);

Return investigational product;

Return diary card;

MDS-UPDRS Part III score before administration of the investigational product and
the background medication for PD (if applicable) (≥12 hours from the most recent
administration
of
background
medication
for
PD
(if
applicable)
and
the
investigational product);

Dispense the drug using the Clinflash IRT system;

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
Take investigational product and background medication for PD (if applicable)
concomitantly;

MDS-UPDRS Part III score after administration of the investigational product and
the background medication for PD (if applicable) (to be performed at 2 ± 1 hours
after the administration);

MDS-UPDRS Parts I, II, and IV scores;

Record concomitant medications/therapies;

Record AEs;

Dispense a new diary card;

Note:
-
At V5 and V6, subjects should return to the study site for a visit in the morning
(recommended from 7:00 a.m. to 10:00 a.m.) with their diary cards and on an
empty stomach (fast for at least 10 hours overnight without depriving of water);
-
The administration of investigational product and last dose of the background
medication for PD (if applicable) on the day before V5 and V6 should be at
least 12 hours apart from the agreed visit time of V5 and V6, and the subject
should bring background medication for PD (if applicable, at least a single dose)
that has been stably taken to the hospital on the day of V5 and V6, and take the
first dose of such medication on the day of V5 and V6 under the guidance of the
investigator.
8.7.2.3 V6 (D84, W12)
At V6, the following procedures will be performed:

Subjects must be fasted before each visit (fast for at least 10 hours overnight without
depriving of water);

Vital signs;

Physical examination;

12-lead ECG;

Laboratory tests: including hematology, blood chemistry, urinalysis, coagulation
function test, and urine pregnancy test (only for women of childbearing potential);

Weight measurement and Ccr calculation;

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
Collect blood samples for exploratory analysis (one blood sample each for
inflammatory indicators and PD biomarkers; among these, 5 mL of blood is
collected for PD biomarker testing and sent to the central laboratory for testing);

Exploratory skeletal muscle mass and function assessment: including ASMI, muscle
strength (grip strength) and 6-meter walking speed test (specific test indicators are
subject to the actual operation of each center). Among them, ASMI is detected and
calculated by DXA, and the calculation formula is ASMI = appendicular muscle
mass (kg) / height2 (m2);

Return investigational product;

Return diary card;

MDS-UPDRS Part III score before administration of the investigational product and
the background medication for PD (if applicable) (≥12 hours from the most recent
administration
of
background
medication
for
PD
(if
applicable)
and
the
investigational product);

Take investigational product and background medication for PD (if applicable)
concomitantly;

MDS-UPDRS Part III score after administration of the investigational product and
the background medication for PD (if applicable) (to be performed at 2 ± 1 hours
after the administration);

MDS-UPDRS Parts I, II, and IV scores;

Record concomitant medications/therapies;

Record AEs;
8.7.3 Follow-up Period (Telephone Follow-up; V7, D91, W13)
At V7, AEs and concomitant medication information will be collected via telephone follow-
up.
8.7.4 Early Withdrawal Visit
Subjects who have early withdrawn from the study should complete the early withdrawal visit
within 7 days after the investigator's awareness (if it is less than 7 days from the date of the

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previous visit, repeated tests of the same item can be waived), excluding subjects who have
early withdrawn from the study due to withdrawal of consent or are lost to the follow-up.
At the early withdrawal visit, the following procedures will be performed:

Subjects must be fasted before each visit (fast for at least 10 hours overnight without
depriving of water);

Vital signs;

Physical examination;

12-lead ECG;

Laboratory tests: including hematology, blood chemistry, urinalysis, coagulation
function test, and urine pregnancy test (only for women of childbearing potential);

Weight measurement and Ccr calculation;

Collect blood samples for exploratory analysis (one blood sample each for
inflammatory indicators and PD biomarkers; among these, 5 mL of blood is
collected for PD biomarker testing and sent to the central laboratory for testing);

Exploratory skeletal muscle mass and function assessment: including ASMI, muscle
strength (grip strength) and 6-meter walking speed test (specific test indicators are
subject to the actual operation of each center). Among them, ASMI is detected and
calculated by DXA, and the calculation formula is ASMI = appendicular muscle
mass (kg) / height2 (m2);

Return diary card;

Return investigational product;

MDS-UPDRS Part III score before the administration of background medication for
PD (only applicable to subject who has received stable medication for PD within at
least 4 weeks prior to study entry, and this score should be ≥12 hours from the most
recent dose of background medication for PD);

Take background medication for PD (only applicable to subject who has received
stable medication for PD within at least 4 weeks prior to study entry);

MDS-UPDRS score: Parts I, II, III, IV (if the subject has received stable medication
for PD within at least 4 weeks prior to study entry, Part III score must be assessed at

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2 ± 1 hours after the administration of background medication for PD at this visit);

Record concomitant medications/therapies;

Record AEs;
8.7.5 Unscheduled Visit
If a subject participates an unscheduled visit at the study site, it should be documented
accordingly.

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9 AE-related Assessment
9.1 Definition of AEs
9.1.1 AEs
An AE is any untoward medical occurrence in a patient administered an investigational
product (TJ0113 capsules or placebo) and which does not necessarily have to have a causal
relationship with this treatment. It can manifest as symptoms, signs, diseases or laboratory test
abnormalities. Therefore, the AE can be any unfavorable or unexpected, or clinically
significant symptoms, signs or diseases, including ADRs, important laboratory abnormal
findings, new diseases during the study, and exacerbation of pre-existing conditions or
symptoms (excluding the conditions to be treated with the investigational product; daily
fluctuation in underlying disease is not considered as an AE).
9.1.2 Treatment-Emergent Adverse Events (TEAEs)
A TEAE refers to any AE that emerges during treatment (absent pre-treatment) or worsens
relative to the pre-treatment state after the first dose of the investigational product.
9.1.3 Treatment-Related Adverse Events (TRAEs)
A TRAE refers to any TEAE related to the investigational product at the investigator’s
discretion.
9.1.4 Serious Adverse Events (SAEs)
An SAE refers to any adverse medical event that results in deatha, is life-threatening eventb,
requires hospitalization or prolongation of existing hospitalization for the subjectc, results in
persistent or significant disability/incapacityd, or is congenital abnormaly or birth defecte, or is
other important medical eventf after the subject uses an investigational product.
Further explanations for the above criteria are as follows:
a.
An AE that results in subject's death;
b.
An AE in which the subjects 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
(e.g., drug-induced hepatitis without liver failure);
c.
Any AEs resulting in hospitalization or prolongation of existing hospitalization
(hospitalization: refers to that a subject has been admitted at the inpatient department

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or emergency ward for observation or treatment over 24 h; prolongation of existing
hospitalization: the AEs occur during hospitalization period and prolong the existing
hospitalization), excluding elective surgery or admission for examination, etc., decided
prior to study participation and for which the treatment is not changed.
d.
The consequences of the AE may cause serious inconvenience or interference with the
subject's normal life and activities, cause impairment, damage or destruction of the
subject's physical function and/or physiological structure, physical activities or quality
of life;
e.
It is suspected that exposure of a parent to the study drug may cause malformation or
congenital functional defect, etc., in the subject's offspring;
f.
Medical and scientific judgment must be exercised in deciding whether expedited
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 be
considered serious if medical intervention is necessary to prevent one of the above
situations. For
example,
important treatment
in emergency
room
or
allergic
bronchospasm
at
home,
cachexia
or
convulsion
requiring
no
hospitalization,
development of drug dependence or addiction etc.
9.1.5 Adverse Drug Reactions (ADRs)
All noxious and unintended responses to a medicinal product related to any dose should be
considered Adverse Drug Reactions (ADRs). There is at least a reasonable possibility of the
causal relationship between the investigational product and an AE, i.e., the relationship cannot
be ruled out.
For a new medicinal product or new usage, all harmful or unexpected reactions at any dose
causally related to administration of the drug in clinical use before approval, particularly in
the period when therapeutic dose has not been determined should be considered ADRs.
9.1.6 Suspected Unexpected Serious Adverse Reactions (SUSARs)
SUSARs
refer
to
suspected
unexpected
serious
adverse
reactions
whose
clinical
manifestations are beyond the Investigator’s Brochure for the investigational drug, package
inserts for marketed medicinal products, summary of product characteristics and other
existing information in terms of their nature and severity.

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Assessment of expectedness: It should be assessed based on the relevant sections of the
Investigator's Brochure for the investigational product that is effective at the date of the event,
which serves as the safety reference information. Unexpected, for the investigational product,
means that the event is not listed on the Investigator's Brochure of the investigational product,
or the nature or severity of the event exceeds that described in the Investigator's Brochure of
the investigational product.
9.2 Causal Relationship
The investigator should conduct a comprehensive analysis according to the specific
circumstances of AEs of the subjects and their past medical history, concomitant diseases and
concomitant medications, to determine the correlation between AEs and the investigational
product. The investigator should perform causality analyses for treatment-emergent symptoms
in order to identify potential correlations between the AE and the investigational product.
The specific criteria for adjudicating the causal relationship between the AE and the
investigational product are shown in Table 9-1. The causal relationship between the AE/SAE
and investigational product is judged as definitely related, probably related, possibly related,
unlikely related and not related. Among them, "definitely related, probably related, and
possibly related" are classified as related to the investigational product, and this type of AEs
are regarded as ADRs. "Unlikely related and not related” are classified as unrelated to the
investigational product, and this type of AEs will not be included in ADR analysis.
Table 9-1 Classification and Rationale for Correlation Determination Results of AEs
in Drug Clinical Studies
5-category
method
Rationale for determination
2-category
method
Definitely
related

Whether there is reasonable temporal relationship

Whether it conforms to the known mechanism of
action, properties of the drug or known adverse
reactions

Positive de-challenge test

Positive re-challenge test
Related

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5-category
method
Rationale for determination
2-category
method

Whether it is not justified by other reasons
Probably
related

Whether there is reasonable temporal relationship

Whether it conforms to the known mechanism of
action, properties of the drug or known adverse
reactions

Positive de-challenge test

Lack of evidence for a positive re-challenge

Whether it is not justified by other reasons
Possibly
related

There is a reasonable temporal relationship;

Lack of evidence for a positive re-challenge;

It is manifested as any of the following conditions:
a)
The AE is consistent with the known mechanism
of
action,
characteristics
or
known
adverse
reactions of the drug, de-challenge test is positive,
but the AE can also be reasonably explained by
other factors;
b)
The AE is consistent with the known mechanism
of
action,
characteristics
or
known
adverse
reactions of the drug, there is a lack of evidence
for a positive de-challenge, and the AE cannot be
reasonably explained by other factors;
c)
The AE
is not
consistent
with the
known
mechanism of action, characteristics or known
adverse reactions of the drug, de-challenge test is
positive, and the AE cannot
be reasonably
explained by other factors;
d)
The AE
is not
consistent
with the
known
mechanism of action, characteristics or known
adverse reactions, there is a lack of evidence for a

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5-category
method
Rationale for determination
2-category
method
positive de-challenge, and the AE cannot also be
reasonably explained by other factors;
Unlikely
related

Temporal relationship cannot be ruled out

Lack of evidence for a positive de-challenge

Lack of evidence for a positive re-challenge

It is manifested as any of the following conditions:
a)
Although the AE is consistent with the known
mechanism of action, characteristics or known
adverse reactions, it can be more reasonably
explained by other factors;
b)
The AE
is not
consistent
with the
known
mechanism of action, characteristics or known
adverse
reactions,
and
can
be
reasonably
explained by other factors;
Unrelated
Not related

There is no reasonable temporal relationship

It does not conform to the known mechanism of
action, properties of the drug or known adverse
reactions

Lack of evidence for a positive de-challenge

Lack of evidence for a positive re-challenge

It can be justified by other reasonable reasons
9.3 Determination of the Severity
The severity of AEs will be recorded according to the National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. For AEs not listed
in NCI-CTCAE, its severity can be graded as follows:

Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations
only; or intervention not indicated.

Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting

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age-appropriate instrumental activities of daily living (instrumental activities of
daily living refer to preparing meals, shopping for groceries or clothes, using the
telephone, managing money, etc.);

Grade 3: Severe or medically significant but not immediately life-threatening;
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care ADL (self-care ADL refer to bathing, dressing and undressing, feeding self,
using the toilet, taking medications, and not bedridden);

Grade 4: Life-threatening, urgent intervention indicated;

Grade 5: Adverse event-related death.
9.4 Collection, Recording and Reporting of AEs
9.4.1 Collection and Recording of AEs and SAEs
9.4.1.1 Collection Time of AEs
AEs are collected in this trial from the time the subject receives the investigational product
(i.e., TJ0113 capsules or placebo) until the end of the follow-up period. Supplementary
description is as follows:

Untoward medical occurrences (including abnormalities at baseline) that newly
occur or worsen relative to pre-signing state from subject's signing ICF to the first
dose of the investigational product, if assessed by the investigator as related to the
subject's participation in this trial (such as a protocol-specified procedure or invasive
test), should be recorded and reported as AEs, otherwise should be recorded as
medical history;

The investigator needs to collect all AEs (regardless of whether it is causally related
to the investigational product or related to clinical procedure) from the first dose of
the investigational product to the end of the follow-up period;

AEs that occur after the follow-up period must also be collected and recorded if the
investigator considers that it is related to the investigational product (including
SAEs) after awareness.
9.4.1.2 Recording of AEs
The investigator or other designee will be responsible for monitoring, recording and reporting
events that meet the definition of AEs/SAEs.
At each visit during the entire study period, the investigator or his/her designee should ask the

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subject non-directive questions to learn about the occurrence of AEs/SAEs, and may also find
AEs/SAEs through the subject’s spontaneous reports, physical examinations, laboratory tests
or other assessments during the visit or non-visit period. The subject or his/her caregiver may
also report AEs occurring during the trial.
For any unexplainable or unexpected laboratory abnormalities of clinical significance
throughout the study period, retest should be performed as soon as possible and the
abnormality should be followed up until returning to the normal range and/or adequate
explanation can be given for the abnormality. The investigator should clearly mark the
laboratory results out of normal range and indicate whether they are of clinical significance or
not.
All AEs must be followed up until they have clinically recovered, stabilized, return to the
screening or baseline level (if baseline level is known), the subject is lost to follow-up (e.g.,
no more information is available or the subject/caregiver refuses to provide any information),
or dead. This means that further follow-up observations may be required even after the last
protocol-specified visit, and the monitoring team may require the investigator to perform
additional follow-up.
All AEs occurring within the collection time limit specified in this protocol must be
completely recorded (after the end of the trial, the collection of follow-up data for subjects
with ongoing AEs does not affect the on-time database lock after the end of the trial).
For the recording of AEs/SAEs, a single diagnosis or syndrome should be used to describe
their term as far as possible. The documentation should be supported by original documents
and each event should be described in detail, including:

Term of AEs (use the term for a sign, symptom, diagnosis, or syndrome);

Onset date, ongoing or not, end date;

Severity;

Investigator's judgment of the causality between the event and investigational
product or study procedure, including details of the suspected procedure;

The actions taken with investigational product may include dose not changed,
temporarily discontinued, dose reduced, drug withdrawn, not applicable, and

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unknown;

Event
outcomes:
①
recovered/resolved;
②
recovering/resolving;
③
not
recovered/not resolved/ongoing; ④recovered/resolved with sequelae; ⑤fatal; and
⑥unknown;

Seriousness: Whether it is an SAE or not;

Drug therapies and other interventions given to correct the AE.
-
None;
-
Drug therapy;
-
Non-drug intervention;
-
Drug therapies and non-drug interventions.
In addition, the investigator should collect other information required by the sponsor.
9.4.1.3 Precautions for Recording of AEs/SAEs
Diagnosis versus signs and symptoms
The diagnosis that is available should be recorded rather than single symptom or sign.
However, if the symptoms and signs cannot be categorized as a single diagnosis during
reporting period, each single event should be recorded as AE or SAE. If the diagnosis is
confirmed later, the AE previously reported based on signs and symptoms should be canceled
and be replaced with an AE report based on a single diagnosis, noting that the start date
should be the start date of the first symptom used for the final diagnosis.
AEs secondary to other events
In general, for events secondary to other AEs (such as cascading events or clinical sequelae),
they should not be recorded as separate AEs, except for severe or serious secondary events. If
the secondary event is medically significant and the two events occurred independently of
each other, the secondary event should be recorded as a separate AE in the eCRF. For example:

If vomiting has caused severe dehydration, two AEs should be separately reported
on the eCRF.

If severe gastrointestinal bleeding has caused renal failure, two AEs should be
separately reported on the eCRF.

If dizziness caused a fall followed by a fracture, three AEs should be separately

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reported on the eCRF.

If neutropenia caused infection, two AEs should be separately reported on the eCRF.

If it is not clear whether the events are interrelated, all AEs should be recorded
separately in the AE Record of the eCRF.
Persistent or recurrent AEs
Persistent AEs are AEs that persist without any remission between the two evaluation time
points of the subject. If the event meets the seriousness criteria, it is an SAE. The investigator
should report it to the sponsor and the Contract Research Organization (CRO) designated by
the sponsor within 24 hours of awareness. In such case, the AE should be updated to change
the AE from "non-serious" to "serious", the date when the AE developed into SAE should be
recorded, and all the information fields related to SAE should be filled in.
Recurrent AEs refer to AEs that have resolved or resolved with sequelae, but then reoccur.
AEs that reoccur should be recorded separately.
Abnormal laboratory values and vital signs
Not all abnormal laboratory values or vital signs are reportable as AEs. An AE must be
reported if the laboratory test or vital sign meets any of the following criteria:

Accompanied by clinical symptoms;

Resulting in changes in the study treatment (e.g. dose adjustment, treatment
interruption or discontinuation);

Requiring medical intervention (e.g., potassium supplementation to treatment
hypokalemia) or resulting in changes in concomitant therapies;

Clinically significant results at the investigator's discretion.
The investigators are responsible for reviewing all the abnormal laboratory findings and vital
signs, and determine whether to record them as AEs.
If clinically significant abnormal laboratory tests or abnormal vital signs are manifestations of
certain disease or syndrome (e.g., alkaline phosphatase and bilirubin increase more than 5
times the upper limit of normal, which are caused by cholecystitis), only the diagnosis is
recorded (i.e., cholecystitis). Conversely, abnormal laboratory tests or abnormal vital signs
should be recorded. Moreover, it should be indicated whether the test value is higher or lower

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than the normal range (for example, it should be recorded as "blood potassium increased"
instead of "abnormal blood potassium"). If there is a standard clinical term corresponding to
abnormal laboratory tests or abnormal vital signs, the clinical term should be recorded. For
instance, serum potassium increasing to 7.0 mEg/L should be recorded as "hyperkalemia".
9.4.2 Reporting of SAEs
For all SAEs that occur within the collection time limit specified in this protocol, the
investigator must fill in, sign and date the SAE Report Form within 24 hours of awareness,
immediately report it to the sponsor (or the CRO appointed by the sponsor).
In case of reports involving death events, the investigator should provide the sponsor and
Ethics Committee with other necessary information, such as autopsy report and final medical
report.
The investigator should provide detailed written follow-up reports in a timely manner. For
follow-up information of SAEs, the reporting method and time limit are the same as those for
the initial report.
Time for collecting SAEs:

Only SAEs related to protocol-specified procedure or invasive test, etc. will be
reported from subject's signing ICF to the first dose of the investigational product.

The investigator needs to collect and report all SAEs (regardless of whether it is
causally related to the investigational product or related to clinical procedure) from
the first dose of the investigational product to the end of the follow-up period;

SAEs that occur after the end of the clinical trial or the end of the follow-up until the
conclusion of the review and approval is obtained, if assessed by the investigator
that the relevance to the investigational product cannot be ruled out, should be
informed to the sponsor (or the CRO appointed by the sponsor) within 24 hours of
awareness.
9.4.3 Reporting of SUSARs
The sponsor (CRO appointed by the sponsor) should comprehensively analyze, evaluate and
judge the safety information received of any sources in a timely manner, including severity,
correlation with the investigational product and whether it is an expected event, as well as

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report in an expedited manner depending on the nature (category) of the event within the time
limit set out by the regulatory authorities. The sponsor (CRO appointed by the sponsor)
should expeditely report SUSARs to all investigators and clinical trial institutions
participating in the study, Ethics Committee, drug regulatory authorities and health authorities
within specified time limit.
The processing and expedited reporting of SUSAR reports will be completed in accordance
with Good Vigilance Practice and FAQs for Expedited Reporting of Safety Data during Drug
Clinical Trials (V2.0).
SUSARs occurring after the end of the clinical trial and before obtaining the approval
conclusion will be reported in the same manner as for expedited reporting before the end of
trial.
For the SUSAR report and clinical trial-related safety information provided by the sponsor,
the investigator should sign and read it in time, and report to the clinical trial institution and
the Ethics Committee.
9.5 Reporting of Special Conditions
9.5.1 Death
Regardless of relevance to the investigational product, all deaths during the trial must be
recorded as SAE (including death due to the disease proposed to be treated with the
investigational product) and reported to the sponsor (or a CRO appointed by the sponsor)
within 24 hours of awareness.
Death should be regarded as the outcome rather than a separate event. Death is not reported as
SAE term, but the cause of death must be reported as the SAE term. Information of events
leading to death can also be further improved in follow-up reports. The term "sudden death" is
used only to describe where a subject with or without pre-existing heart disease died suddenly
and accidentally within 1 hour of onset of the acute symptoms, and the cause of death is
presumed to be the heart disease; or the subject died without any witness within 24 hours after
the subject is last seen (when the subject's vital signs are stable). If the cause of death cannot
be determined at the time of reporting, the SAE term may be recorded and reported as “death

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unexplained”. If the cause of death is subsequently established (e.g., after an autopsy), the
SAE term should be replaced with the established cause of death.
9.5.2 Pregnancy
If the female subject of childbearing potential or the female partner of a male subject becomes
pregnant from the first dose of investigational product to within 6 months after the last dose of
the investigational product, the investigator should be immediately informed. The investigator
should complete the Clinical Trial Pregnancy Report Form within 24 hours of awareness, sign
and date, and report it to the sponsor (or the CRO appointed by the sponsor) by email. All
pregnancy events should be followed up until the pregnancy outcome or lost to follow-up.
In the case of live birth, the case must be followed up until 30 days after the birth of the baby.
Spontaneous abortion or termination of pregnancy for medical reasons (except for
uncomplicated elective abortion for non-medical reasons) should be considered as an SAE,
that is, the SAE should also be reported at the same time as the completion and reporting of
the pregnancy report form. Any birth defects/congenital abnormalities of newborns, stillbirth,
death, and serious complications during pregnancy of female subjects or female partners of
male subjects and of newborns, etc., if meeting the SAE criteria, are also considered as SAEs,
that is, SAEs should also be reported at the same time as the completion and reporting of the
pregnancy report form.
Pregnant female subjects must immediately discontinue the investigational product and
withdraw from the trial. The male subject whose partner becomes pregnant does not have to
withdraw from this study. The investigator should provide recommendations for the male
subject and his female partner, discussing risk of continued pregnancy and potential effect on
the fetus.
9.5.3 AEs Related to Overdose or Medication Error
Medication error is defined as an unexpected deviation in the administration of the
investigational product, such as an omission, incorrect medication dose (e.g., overdose),
wrong time of administration, wrong route of administration, wrong medication, and use of
expired/contaminated/deteriorated study drug, among which, overdose is defined as the actual

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dose of the investigational product administered being greater than the planned dose.
Overdose or medication error of investigational product itself is not an AE, but it may lead to
an AE. All AEs related to overdose or medication error of the investigational drug should be
recorded on the AE Record of the eCRF. If the relevant AE meets the seriousness criteria for
SAE, it should be reported to the sponsor immediately (i.e., within 24 hours of awareness).

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10 Data Management
10.1 Completion and Transfer of Source Data and Case Report Form
Data in eCRF are all from source data and documents. They are filled in by the investigator or
the person designated by the investigator. Information completeness and accuracy must be
ensured. If there is any error that needs to be corrected, the modification should be carried out
according to the eCRF completing instructions, and the name of data modifier and
modification date should be recorded. After filling in the eCRF, it should be submitted timely
to Electronic Data Capture (EDC) system via the Internet. After the data in the EDC system
are confirmed correct after source data verification (SDV), review and query by data manager,
the investigator is required to provide electronic signature for confirmation before data
locking.
10.2 Design and Establishment of Database
The database is established by the data department of the CRO assigned by the sponsor. The
database should manage the system login, data entry, modification, deletion and other data
traces.
10.3 Data Entry and Modification
In this trial, data are collected using EDC, and online data management is completed through
the functions of electronic data entry, data verification and data inspection of EDC system.
Data in eCRF should be filled in by the investigator or the person designated by the
investigator. Information completeness and accuracy must be ensured. If there is any error
that needs to be corrected, the modification should be carried out according to the instructions
for filling out the eCRF, and the EDC system would automatically record the name of data
modifier and modification date.
The eCRF, once completed, will be timely submitted through the network to EDC system.
After data in the EDC system are verified against the source data, reviewed by DM, and the
queries are well resolved, the investigator will confirm it by providing an electronic signature
before data lock.

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10.4 Data Review
After data entry and verification are completed, the data manager, the principal investigators,
the sponsor, and statistical analysis personnel will jointly review the data, and complete the
final definition and judgment of the analyzed population.
10.5 Data Coding
The data manager is responsible for medical coding. Coding contents include medical history,
concomitant medications and AEs.
The medical history and AEs will be coded according to Medical Dictionary for Regulatory
Activities (MedDRA). The concomitant medications are coded using World Health
Organization Drug Dictionary (WHO DD). All dictionaries used are the latest version
confirmed by the sponsor.
During the coding process, the data manager will ask the investigator, in the form of data
queries, to verify and confirm any data problems such as failure to code due to improper,
inaccurate, and vague medical terms provided.
Prior to database lock, the data manager will send medical coding report to the sponsor, which
will be reviewed by the sponsor.
10.6 Data Lock
Database can be locked when the following conditions are met:
1)
All data have been entered into database;
2)
All questions have been resolved;
3)
The analysis population has been defined and evaluated.
At the end of the study, once the accuracy of the established database is confirmed through a
data verification meeting, the principal investigator, the sponsor, and the statistical analysts
jointly lock the database. In principle, any changes to the locked database are not allowed.
After database locking, if any data errors are identified, the project team (sponsor, statistical
analyst, clinical team, data manager, etc.) will discuss and decide whether the database needs
to be unlocked. If the sponsor confirms that the data are of vital importance to statistical

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analysis and must be corrected, the DM should complete the database unlocking application
form and send it to the sponsor for approval, and then unlock the database. If it is confirmed
after evaluation that unlocking is not necessary, the application and approval form for hard
code implementation should be completed and sent to the statistical analyst. The statistical
analysts perform statistical analysis for database according to the SAP.

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11 Statistical Analyses
11.1 Sample Size
The sample size of this study is not determined based on the formal statistical assumptions
and it is expected to include approximately 150 subjects with early-stage PD, who will be
randomized in a 1:1 ratio into two cohorts (Cohort 1: 200 mg dose group; Cohort 2: 400 mg
dose group). Within each cohort, the subjects will be randomized into the TJ0113 capsules
group and the placebo group in a ratio of 2:1, with approximately 50 subjects receiving
TJ0113 capsules and approximately 25 subjects receiving the placebo. In this study, there will
be approximately 50 subjects in each of the TJ0113 capsules 200 mg group, TJ0113 capsules
400 mg group and the placebo group.
11.2 Statistical Analysis Population
Full analysis set (FAS): including all randomized subjects who have received at least one dose
of investigational product.
Per-protocol set (PPS): including subjects in the FAS who have not experienced major
protocol deviations that affect the primary efficacy endpoint.
Safety set (SS): including all subjects who have received at least one dose of the
investigational product and have undergone at least one post-dose safety assessment.
Demographics and baseline characteristics will be analyzed based on FAS, the efficacy
analyses will be performed based on both FAS and PPS, and the safety analyses will be
performed based on SS.
11.3 General Analysis
Statistical analyses of efficacy and safety will be performed using the SAS software (V9.4 or
later).
Unless otherwise specified, descriptive statistics for continuous variables included the number
of subjects (n), mean, standard deviation (SD), median, first quartile (Q1), third quartile (Q3),
minimum (Min), and maximum (Max). Categorical variables will be summarized using
descriptive statistics including number of subjects (n) and the percentage (%).
Unless otherwise specified, it will be summarized by the TJ0113 capsules 200 mg group,

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TJ0113 capsules 400 mg group, and the placebo group.
11.4 Statistical Analysis Methods
11.4.1 Demographics and Baseline
Demographic and baseline characteristics will be summarized using descriptive statistics.
Baseline is defined as the last valid measurement or assessment (if applicable) before the first
dose of the study drug.
11.4.2 Analysis for Primary Endpoint
The primary objective of this study is to assess the efficacy of TJ0113 capsules in the
treatment of patients with early-stage PD. The main concern of interest is the treatment
difference in terms of the changes from baseline in the MDS-UPDRS Part III (motor
examination) scores after 12 weeks of treatment between the TJ0113 capsules group and the
placebo group.
Definition of estimand:

Population: patients with early-stage PD

Endpoint: changes from baseline in scores of MDS-UPDRS Part III (motor
examination) after 12 weeks of treatment. Evaluation time point: ≥12 hours from
the most recent dose of anti-PD drug.

Treatment: treatments will be randomly assigned; subject will be randomized in a
1:1 ratio to two cohorts (200 mg dose group and 400 mg dose group); and within
each cohort, the subjects will be randomized in a 2:1 ratio to the TJ0113 capsules
group and the placebo group.

Concomitant event and management strategy: For any concomitant medication
(excluding the investigational product and stable anti-PD medications at the time of
enrollment) or treatment that could potentially impact the PD disease process, a
therapeutic strategy will be employed.

Population-level summary: differences in the least square mean of the changes from
baseline in MDS-UPDRS Part III (motor examination) scores after 12 weeks of
treatment between the TJ0113 capsules group and the placebo group.
The analysis will be performed using a mixed models for repeated measures (MMRM) with
the changes from baseline in the MDS-UPDRS Part III scores after 12 weeks of treatment as

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the dependent variable, whether subjects have been receiving levodopa, the background
medication for PD (yes vs. no) at a stable dose at baseline and the baseline MDS-UPDRS Part
III score as the covariates, and the treatment group, visit, and the treatment group-by-visit
interaction as the fixed effects.
11.4.3 Sensitivity Analysis
The sensitivity analysis of the primary endpoint will be performed using the analysis of
covariance. The model will use the changes from baseline in the MDS-UPDRS Part III scores
after 12 weeks of treatment as the dependent variable, whether subjects have been receiving
levodopa, the background medication for PD (yes vs. no) at a stable dose at baseline, the
baseline MDS-UPDRS Part III score, and the treatment group as the covariates.
After the primary endpoint is imputed by using different mechanisms for imputing the
missing data, the sensitivity analysis will be performed using the same method as that for the
primary analysis. Detailed statistical methods will be described in a separate SAP.
11.4.4 Analysis for Secondary Endpoints
11.4.4.1 Analysis of Efficacy
The secondary efficacy endpoints will be summarized using the same statistical methods
described above for primary endpoint.
11.4.4.2 Safety Analysis
It includes AEs and other safety-related parameters, which will be summarized by the
descriptive statistics.
Detailed statistical methods will be described in a separate SAP.
11.4.5 Analysis for exploratory endpoint
Exploratory endpoint (inflammatory indicators, α-synuclein, GFAP, ASMI, grip strength, 6-
meter walking speed) will be analyzed using the analysis of variance or nonparametric tests,
and the correlations between the parameters will be analyzed using the Spearman's or
Pearson's correlation coefficients. Detailed statistical methods will be described in a separate
SAP.

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11.4.6 Sub-group Analysis
Sub-group analyses will be performed for the primary endpoint, where data are available, and
specific sub-group information will be described in a separate SAP.

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12 Trial Management
12.1 Statement
This clinical study will be conducted according to the standard operating procedures of the
sponsor and CRO. The procedures are established aiming at guaranteeing that this study can
be conducted in accordance with the requirements of Declaration of Helsinki, E6 Guidelines
for Good Clinical Practice issued by the International Council for Harmonization of Technical
Requirements for Pharmaceuticals for Human Use (ICH), GCP issued by NMPA and all
applicable regulations.
If the investigators sign the protocol, it means that they will agree to conduct this study in
strict accordance with the protocol, clinical trial principles and relevant laws and regulations.
All materials and information provided by the sponsor are kept according to the
confidentiality requirements.
12.2 Ethical Considerations
This study is designed and prepared on the basis of Declaration of Helsinki of World Medical
Association after the consideration of rights and welfare of patients. The principal investigator
or investigator of the clinical trial will explain objective and all potential possibilities of the
trial to patients. Those patients who voluntarily agree to participate in the clinical trial and
sign the ICF will become subjects.
The investigators and personnel participating in this study should appropriately understand
and be familiar with study plan, and prepare in advance, such as for treatment measures in
case of unexpected AEs, required reports and sufficient training. The clinical investigators
must conduct clinical trials in strict accordance with Declaration of Helsinki, E6 Guidelines
for Good Clinical Practice issued by ICH, Good Clinical Practice (GCP) issued by NMPA and
applicable laws and regulations.
The investigators and personnel participating in this study should conduct this study
according to the contents of study protocol by scientifically using the currently recognized
technical level.
According to the national policies and regulations, the investigator should provide trial-related

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documents for the Ethics Committee.
The approval of the Ethics Committee and drug regulatory authorities must be obtained
before the initiation of clinical study.
Modifications to the study protocol should be submitted to the Ethics Committee for approval
and sent to Health Authorities (HA) for record keeping according to the local requirements.
During the clinical study period, should any SAEs or unexpected AEs which are associated
with clinical study safety and may affect the safety of subjects and study implementation
occur, the investigators should report to the Ethics Committee according to the regulatory
requirements.
After the study is completed, the Ethics Committee (EC) should be informed.
12.3 Source Data Verification
The Investigator must properly handle all data obtained during the clinical study to guarantee
the rights and privacy of subjects. The investigators must allow the CRAs/auditors/inspectors
to review and check the required clinical study documents so as to verify the accuracy of the
source data and learn about the study progress. If the source data cannot be verified, the
investigator should agree to assist the CRAs/auditors/inspectors in the further confirmation of
data quality control.
12.4 Quality Assurance/Audit
The quality of all drugs and supplies used in the clinical study must be controlled. The
sponsor and its authorized personnel or relevant medical management institutions have the
right to review the clinical study, which aims at ensuring that the data recorded in clinical
study are accurate and the study is conducted in accordance with the clinical study protocol.
This study will be organized, performed and reported according to the study protocol as well
as the standard operating procedures (SOPs) of the sponsor and CRO. In ICH E6, the
definition of quality assurance (QA) is “all those planned and systematic actions that are
established to ensure that the trial is performed and the data are generated, documented
(recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable
regulatory requirement(s).” The QA work of the sponsor will be carried out in accordance

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with the study auditing plan. According to the requirement of ICH E6 section 5.19.3 (b), the
sponsor’s audit plan and procedures for a trial audit should be guided by the importance of the
trial to submissions to regulatory authorities, the number of subjects in the trial, the type and
complexity of the trial, the level of risks to the trial subjects, and any identified problem(s).
The QA work can be outsourced to a CRO or an independent consulting agency. It is required
that the investigator should support audit, attend audit activities according to the requirements
of auditors, allow auditors to directly access to original data/document, including all medical
records, documents and letters related to the study and ICFs of the clinical trial, etc. The
clinical trial subjects will be informed of such clinical study inspecting or auditing process,
but the privacy and data materials of subjects will be strictly protected.
12.5 Informed Consent
The investigators are responsible for explaining the purposes, methods, benefits and potential
risks of this clinical trial, other optional treatment methods, rights and obligations to each
subject meeting the requirements of the Declaration of Helsinki. The subjects should be
informed that they have rights to withdraw from this trial at any time. Signed ICF must be
obtained from the subject before any study-specific procedures.
Verbal explanation must be provided when obtaining written informed consent from the
subject. The informed consent form must be dated and signed by each subject or impartial
witness. One of the signed ICF (including information page) will be kept by the subject and
the other will be kept by the study site as study archives.
Before any study related procedure, the ICF must be agreed on and signed by the subject or
impartial witness. Before obtaining informed consent, the investigator or designated personnel
should provide the subject with sufficient time and opportunity to ask about details of the trial
and decide whether to participate in this trial or not. The process of the informed consent
should be documented in the progress note at the day of screening visit or medical records.
The investigator should be responsible for the process of informed consent. If any information
related to the subject's willingness to continue participating in the trial is available during the
trial, the written ICF must be updated and provided to the subject to confirm if the subject is

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willing to continue. Ethical approval has to be obtained for the revised ICF before providing
to subjects.
After signing the ICF, the subjects must also agree that the sponsor, drug approval regulatory
authorities, auditors and/or the sponsor-authorized clinical trial CRAs check the available
source data related to clinical study. Moreover, the reviewer must follow confidentiality
statement.
12.6 Trial Protocol Revision Rules
After this protocol has been approved by the Ethics Committee, in case any amendment has
been made to the protocol during the conduct of the study, the amendment can be
implemented only after being submitted to the Ethics Committee and the approval is obtained.
Any changes to the protocol are required to be made in a written form, regardless of major or
non-major protocol amendments. Substantive protocol modifications which may definitely
affect the safety of subjects, study scope or scientific quality of this study should be approved
by the Ethics Committee of all study sites. In order to protect the safety of all subjects in this
study, the investigators or sponsor should not be prevented to take any emergency measures
by the limitation of the above requirements. If the investigators consider that protocol
modifications must be immediately made for the consideration of safety, they must
immediately notify the institutions designated by the sponsor and inform the Ethics
Committee of study sites according to the policies stipulated by EC who approves this study,
local regulations and policies. Any changes which affect study administration only do not
require substantive protocol modifications or EC approval, however, these changes must be
reported to EC. Under these conditions, the sponsor will send an authentication letter to EC to
carefully specify these changes.
12.7 Protocol Deviations
The investigator has to conduct this clinical trial according to the clinical study protocol
approved by the EC and GCP regulations. The protocol is established to make the investigator
follow regulations in ICH E6 Section 4. During the trial, the investigator should avoid
protocol deviations, except emergency actions taken to avoid direct harm to subjects. In case

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of other unexpected situation requiring deviation from protocol-specified procedures, the
investigator should discuss with the medical personnel (and the Ethics Committee when
necessary) to determine appropriate measures.
All protocol deviations should be recorded by the study site, including but not limited to time
of protocol deviation, time of awareness, description of event and action taken. In case of a
significant protocol deviation, the medical personnel, CRA, and EC should be notified in a
timely manner.
If a subject withdraws from the trial early due to withdrawal of consent or loss to follow-up,
and fails to complete the early withdrawal visit and post-treatment follow-up as specified in
the protocol, it will not be recorded as a protocol deviation, but the investigator must make
corresponding records in the medical records.
12.8 Case Report Form
The database programmer of CRO will establish eCRF in the Clinflash system. Different
subjects are identified on the eCRF only by appropriate identification codes (e.g., site No. and
subject number). The eCRFs are used for the documentation of clinical study data of subjects,
and are a component of this study and relevant study reports. Entry must be therefore accurate
and complete. The eCRFs are entered into Clinflash system by the investigator or personnel
authorized by the investigators (indicated in the study authorization table). It must be ensured
that all data entry is completed and stored. The investigator must state that all information in
eCRF is true by electronic signature.
In clinical study, eCRF should be completed as soon as possible after each visit to record the
condition of subjects.
The medical records and other records related to disease progression of subjects during the
study period will be stored by the investigators. These records should contain the following
contents: original or copy of laboratory data and other medical test results (e.g., 12-lead ECG,
etc.). These materials must be stored at the site with subjects' medical records.
12.9 Monitoring
Monitoring will be conducted by the sponsor or its commissioned CRO.

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Before certain study site is selected to participate in this study, one site selection visit will be
performed to confirm that such site, equipment and site personnel meet protocol requirements
and GCP.
During the study period, the monitors should routinely perform on-site monitoring. At each
monitoring, visit date will be documented at site visit records of the study sites. The sponsor
shall determine whether to perform site monitoring based on the quality of the study.
CRA’s study monitoring activities include:

Perform study initiation visit to the study site, collect and distribute necessary
documents before study; provide guidance and description of the protocol, study
procedure and expectation to investigators and site staff; obtain investigators'
guarantee of conducting the trial in compliance with study requirements and the
GCP and introduce study materials to investigators and corresponding study staff.

Monitoring visit: According to the requirements of GCP, CRAs taking part in the
current study should completely understand affairs of confidentiality and compare
the data in the eCRF with those in the hospital or clinical record (source documents).
Before the initiation of the study, the CRA should discuss the specific items required
as source documents with the investigator and confirm the nature and storage place
of all source documents, so as to guarantee that the sponsor or the investigator could
know the origin of source data for eCRF completion, and the CRA authorized by the
sponsor has the right to check and verify the data. All observations and findings
during the monitoring process must be verified. If the electronic records are stored at
study institutions, the verification methods must be discussed with the study
personnel.
Source documents must be available for confirming:

The identity of subject, whether the subjects are qualified and participate the study
or not;

Appropriate informed consent procedure;

Visit date;

Records of safety and efficacy parameters;

Sufficient reports and visits of AEs;

Treatment with concomitant medications;

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
Records of receipt/dispensing/return of drugs;

Administration information of investigational product;

Subjects’ completion of treatment, termination of treatment or withdrawal from the
study and appropriate reasons;

The data are authentic, accurate and complete;

Subjects’ safety and rights are protected;

Investigator’s implementation complies with the currently approved protocol, GCP
and all relevant regulatory requirements.
Objectives that the monitoring should realize include:

Check and assess the trial progress;

Review the collected trial data;

Carry out verification of source documents;

Identify any problems and develop solutions.
During the study period, CRAs are required to directly review all related documents with the
consent of the investigator. The investigators should ensure that they and relevant study
personnel should regularly meet with CRAs to discuss findings during monitoring visits and
related issues.
12.10 Intellectual Property
All study materials on study drug, such as patent application, dosage form, manufacturing
process, basic research, etc., are considered confidential as long as they are not published. All
information obtained from the trial sponsor and the trial belongs to the intellectual property
rights of the trial sponsor. Therefore, all relevant personnel of the clinical trial must strictly
keep it confidential, and should not disclose it to any third party without the prior consent of
the sponsor. It should not be used for other purposes other than the study.
12.11 Subject's Privacy
Study personnel must ensure to protect privacy of subjects in the clinical trial. In all eCRFs,
documents and files submitted to sponsor, the clinical trial subjects can only be identified by
clinical trial screening number. Full name of a subject is never indicated. The investigator
must store the private information, e.g., name and address, of the subjects in the clinical trial

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in a strictly confidential manner, and may not submit it to the sponsor.

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13 Paper Publications
The study data and manuscript obtained in this study will also be considered confidential.
Hangzhou PhecdaMed Co., Ltd., as the sponsor, has the exclusive right to this trial and has
the right to decide to disclose it to other clinical study staffs and national regulatory agencies.
Authors and the manuscript will reflect coordination between investigators and study sites and
staff of the Sponsor. Authors will be identified before drafting of the manuscript. Many study
sites are participating in this study, unless prior consent has been obtained from the Sponsor,
individual shall not publish any data related to the clinical study before the final report of the
multi-center study has been completed. The sponsor has the right of final decision about the
manuscript and publication.

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14 Clinical Data Archiving
14.1 Source Data and Source Documents
In this trial, source data includes records on the clinical findings, observations, and other
activities required to reconstruct and evaluate the clinical trial. The original data is contained
in the source files.
The source files involved in the clinical study are original records, documents and data (such
as hospital medical records, medical images, laboratory records, memos, subject diaries or
assessment forms, drug distribution records, data automatically recorded by instruments,
subject files, clinical trial-related documents and records kept by pharmacies, laboratories,
and medical technology departments, including certified copies, etc.). Source documents must
be retained to support the information provided in eCRFs.
14.2 Data Archiving of Study Site
14.2.1 Materials related to the Ethics Committee
Personnel responsible for data storage at the study site must keep records and synopsis of EC
meetings till 5 years after termination or completion of the study. If the sponsor wishes to
retain for a longer period, the two parties will discuss and decide the retention duration and
methods. If the study site makes any changes in document retention, personnel or investigator
responsible for document retention should contact the sponsor.
14.2.2 Materials related to Trial Conduct
The personnel in charge of materials preservation in the study site must keep the following
files until 5 years after the investigational drug is approved for marketing. If the sponsor
wishes to retain for a longer period, the two parties will discuss and decide the retention
duration and methods. If the study site makes any changes in document retention, personnel
or investigator responsible for document retention should contact the Sponsor.

Original materials;

Trial contract, original copy or copies of the ICF, other GCP-related materials
provided by the site staff;

Study protocol, GCP-related materials obtained from the EC, or other GCP-related
materials obtained;

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
Records of management of the investigational product and other records related to
trial conduct.
14.3 Data Archiving of Sponsor
The sponsor will store the following materials (including documents and data) until 5 years
after the investigational drug is approved to be marketed. A longer retention period may be
required according to relevant regulations. It is the responsibility of sponsor to inform the
investigator/study site as to when such data is no longer required to be retained:

Study protocol, trial agreement, the original or duplicate copies of the study reports,
or GCP-related materials provided by the sponsor;

Case report form, GCP-related notifications, or GCP-related materials obtained from
the investigators;

Monitoring and audit records, or other relevant operation records;

Data obtained in the trial;

Relevant records specified in GCP.

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15 Protocol Amendments
After this protocol has been approved by the Ethics Committee, if any modifications should
be made, the protocol amendment statement should be drafted and signed by the principal
investigator. Protocol amendment is allowed after the approval of the sponsor. Protocol
amendment can be implemented after being reviewed or archived by the EC.
Protocol/Amendment
Version
Formulation Date
Revised Content
TJJS01-201
V1.0
August 19, 2024
Initial version
TJJS01-201
V2.0
September 24, 2024
See corresponding
amendment record
d
f
TJJS01-201
V3.0
December 20, 2024
See
corresponding
d
TJJS01-201
V4.0
February 17, 2025
See
corresponding
d
t

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16 References
[1] Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's
disease. Mov Disord. 2015;30(12):1591-1601. doi:10.1002/mds.26424.
[2] Chaudhuri KR, Healy DG, Schapira AH; National Institute for Clinical Excellence.
Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol.
2006;5(3):235-245. doi:10.1016/S1474-4422(06)70373-8.
[3] Haibo Chen, Dongdong Wu. Guideline for primary care of Parkinson ′ s disease
(2019) [J]. Chinese Journal of General Practitioners, 2020 (1): 5-17.
[4] Zhang ZX, Roman GC, Hong Z, et al. Parkinson's disease in China: prevalence in
Beijing, Xian, and Shanghai. Lancet. 2005;365(9459):595-597. doi:10.1016/S0140-
6736(05)17909-4.
[5] Yanan Xu, Zhigang Zhao. Therapeutic Evaluation of Anti-Parkinson's Disease Drugs
and Research and Development of New Drugs [J]. Herald of Medicine, 2023, 42 (8):
1178-1186.
[6] Parkinson’s Disease and Movement Disorders Group of Neurology Branch of
Chinese Medical Association, Parkinson’s Disease and Movement Disorders Group of
Neurologist Branch of Chinese Medical Doctor Association. Guidelines for Therapeutic
Management of Parkinson’s Disease in China (Version 4) [J]. Chinese Journal of
Neurology, 2020, 53(12): 14
[7] Ying Wang, Qiang Zhang, Weidong Le. Involvement of mitophagy in pathogenesis
of Parkinson disease [J]. Chinese Journal of Clinicians (Electronic Edition), 2015, 9 (21):
7.
[8] Zhang L, Dai L, Li D. Mitophagy in neurological disorders. J Neuroinflammation.
2021 Dec 22;18(1):297.
[9] Asano T，Koike M,Sakata S, et al. Possible involvement of iron-induced oxidative
insults in neurodegeneration.[J]. Neurosci Lett,2015,588: 29-35.

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[10]Alvarez-Erviti L, Rodriguez-Oroz MC,Cooper JM, et al. Chaper-one-mediated
autophagy markers in Parkinson disease brains[J].Arch Neurol,2010,67:1464-1472.
[11]Wasner K, Smajic S, Ghelfi J, Delcambre S, Prada-Medina CA, Knappe E, Arena G,
Mulica P, Agyeah G, Rakovic A, Boussaad I, Badanjak K, Ohnmacht J, Gérardy JJ,
Takanashi M, Trinh J, Mittelbronn M, Hattori N, Klein C, Antony P, Seibler P, Spielmann
M, Pereira SL, Grünewald A. Parkin Deficiency Impairs Mitochondrial DNA Dynamics
and Propagates Inflammation. Mov Disord. 2022 Jul;37(7):1405-1415.
[12]Miller S, Muqit MMK. Therapeutic approaches to enhance PINK1/Parkin mediated
mitophagy for the treatment of Parkinson's disease. Neurosci Lett. 2019 Jul 13;705:7-13.

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17 Appendices
17.1 Appendix I: Definition of Women of Childbearing Potential and Contraceptive
Requirements for Subjects
Definition of women of childbearing potential
Woman of childbearing potential (WOCBP) is defined as any female who have not undergone
sterilization and are able to become pregnant anatomically and physiologically after menarche
and before menopause.
Women
without
childbearing
potential
are
defined
as
postmenopausal
women
or
premenopausal women who have undergone sterilization procedure.
Postmenopause is defined as menopause for ≥12 months without alternative medical
treatment.
Sterilization procedures include bilateral tubal ligation or bilateral oophorectomy or
hysterectomy.
Requirements for contraception
In the whole study period and up to 6 months after the last dose of the investigational product,
subjects and their partners must agree to one of the following operations:

Complete abstinence of subjects and their partners. Periodic abstinence (e.g.,
calendar, ovulation, symptothermal or post-ovulation methods) is not allowed; or

Correct use of one of the contraceptive methods with a failure rate of < 1%:
-
Intrauterine device or intrauterine hormone-releasing system with an annual failure
rate of < 1% for subjects or their partners;
-
Vasoligation for subjects or their partners;
-
Subjects use double barrier method: Condoms and/or occlusion caps (diaphragm or
cervical
cap/dome
cap),
spermicide
(foam/gel/film/cream/suppository)
barrier
method should be used as supplementary measures.

Investigational Drug/Study Phase: TJ0113 Capsules/Phase II
Protocol No.: TJJS01-201
Version 4.0/date: February 17, 2025
Confidential
17.2 Appendix II: Calculation of Ccr
Ccr as calculated using the Cockcroft-Gault formula:
Ccr (mL/min) = (140-age (year)) × weight (kg)/72 × serum creatinine (mg/dL) (× 0.85, for
female)
Ccr (mL/min) = (140-age (year)) × weight (kg)/0.814 × serum creatinine (μmol/L) (× 0.85,
for female)