A Multicentre, Open-label, Single-arm Study to Investigate the Efficacy and Safety of Triptorelin Pamoate 22.5 mg 6-month Formulation in Chinese Patients With Locally Advanced or Metastatic Prostate Cancer
Phase: PHASE3
Conditions: Advanced Prostate Cancer, Metastatic Prostate Cancer, Locally Advanced Prostate Cancer
Sponsor: Ipsen

 
D-CN-52014-237 
CONFIDENTIAL 
PROTOCOL: FINAL with Amendment 3: Version 4.0, 08 March 2024 
PAGE 1/92 
 
080004-FOR Ipsen Protocol template version 8.0 
Protocol Title:  
A multicentre, open-label, single-arm study to investigate the efficacy and safety of triptorelin 
pamoate 22.5 mg 6-month formulation in Chinese patients with locally advanced or metastatic 
prostate cancer  
 
Protocol Number: D-CN-52014-237 
 
Compound: Triptorelin pamoate (embonate) salt (IPN52014) 
 
Short Title: Effects of triptorelin pamoate 6-month when given to adult Chinese participants 
with advanced cancer in the prostate 
 
Study Phase: IIIb 
 
Sponsor Name: Ipsen Pharma 
 
Legal Registered Address: 
Ipsen Pharma 
65, quai Georges Gorse 
92100 Boulogne Billancourt, France  
 
Regulatory Authority Identifier Number(s) 
Not applicable 
 
Date: 08 March 2024  
 
Version Number: 4.0 
Amendment Number: 3  
 
Persons supplied with this information must understand that it is strictly confidential. 
Information contained herein cannot be disclosed, submitted for publication or used for any 
purpose other than that contemplated herein without the sponsor’s prior written 
authorisation.

I P S E N G R O U P 
D -C N -5 2 0 1 4 -2 3 7  
C O N FI D E N TI A L  
P R O T O C O L: FI N A L  wit h A m e n d m e nt 3: Versi o n 4. 0, 0 8 M arc h  2 0 2 4  
P A G E 2 /9 2  
 
 
S p o ns or Si g n at or y:  
 
 
Me dical De v el o p me nt Direct or  
R & D S ha n g hai I n n o v ati o n H u b I pse n ( S ha n g h ai) 
U nit 0 1,  1 5t h Fl o or  
N o. 2 1 8, X ujia h ui R oa d  
H ua n g p u District  
S ha n g hai 2 0 0 0 0 1  
C hi na  
 
D ate  
 
 
Me dic al M o nit or N a me a n d C o nt act I nf or m ati o n:  
 
Me dical De v el o p me nt Direct or  
R & D S ha n g hai I n n o v ati o n H u b I pse n ( S ha n g hai)  
U nit 0 1,  1 5t h Fl o or  
N o. 2 1 8, X ujia h ui R oa d  
H ua n g p u District  
S ha n g hai 2 0 0 0 0 1  
C hi na  
Tele p h o ne: 
 
P P D
P P D
P P D

IPSEN GROUP 
D-CN-52014-237 
CONFIDENTIAL 
PROTOCOL: FINAL with Amendment 3: Version 4.0, 08 March 2024 
PAGE 3/92 
 
 
Principal Investigator Signature Page 
I have read and agree to Protocol D-CN-52014-237 entitled “A multicentre, open-label, 
single-arm study to investigate the efficacy and safety of triptorelin pamoate 22.5 mg 6-month 
formulation in Chinese patients with locally advanced or metastatic prostate cancer” with 
protocol Amendment #3. I am aware of my responsibilities as an investigator under the 
guidelines of Good Clinical Practice (GCP), local regulations (as applicable) and the study 
protocol. I agree to conduct the study according to these guidelines and to appropriately direct 
and assist the staff under my control, who will be involved in the study. 
 
NAME:  
[ ] 
TITLE: 
[PRINCIPAL] 
SIGNATURE: 
 
INVESTIGATOR 
 
DATE: 
 
OFFICE: 
[ ] 
 
[ ] 
 
[ ] 
 
[ ] 
 
[ ] 

IPSEN GROUP 
D-CN-52014-237 
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PAGE 4/92 
 
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES  
DOCUMENT HISTORY 
Document 
Version 
Date 
Status 
Amendment 3 
4.0 
08 March 2024 
Effective 
Amendment 2 
3.0 
07 April 2022 
Superseded 
Amendment 1 
2.0 
11 November 2021  
Superseded 
Original Protocol 
1.0 
31 July 2019 
Superseded  
 
Amendment 3 (08 March 2024) 
 
Overall Rationale for the Amendment: 
Protocol was updated to clarify ambiguous wording/text in the protocol and the safety/full analysis set. 
 
Summary change table from previous version of the protocol 
Any new or amended text in the protocol is indicated in bold. Deletions are marked in strikeout text. Minor formatting and editing are not included. 

IPSEN GROUP 
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PROTOCOL: FINAL with Amendment 3: Version 4.0, 08 March 2024 
PAGE 10/92 
 
 
TABLE OF CONTENTS 
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................................... 4 
TABLE OF CONTENTS ....................................................................................................... 10 
LIST OF ABBREVIATIONS ................................................................................................ 14 
1 
PROTOCOL SUMMARY ........................................................................................... 16 
1.1 
Synopsis .......................................................................................................................... 16 
1.2 
Schema ........................................................................................................................... 19 
1.3 
Schedule of Activities (SoA) ......................................................................................... 20 
2 
INTRODUCTION ........................................................................................................ 25 
2.1 
Study Rationale ............................................................................................................. 25 
2.2 
Background ................................................................................................................... 25 
2.3 
Benefit/Risk Assessment ............................................................................................... 27 
2.3.1 
Risk Assessment .......................................................................................... 27 
2.3.2 
Benefit Assessment ...................................................................................... 27 
2.3.3 
Overall Benefit: Risk Conclusion ............................................................... 28 
3 
OBJECTIVES AND ENDPOINTS ............................................................................. 29 
4 
STUDY DESIGN ........................................................................................................... 31 
4.1 
Overall Design ............................................................................................................... 31 
4.2 
Scientific Rationale for Study Design .......................................................................... 31 
4.3 
Justification for Dose .................................................................................................... 32 
4.4 
End of Study Definition ................................................................................................ 32 
5 
STUDY POPULATION ............................................................................................... 33 
5.1 
Inclusion Criteria .......................................................................................................... 33 
5.2 
Exclusion Criteria ......................................................................................................... 33 
5.3 
Lifestyle Considerations ............................................................................................... 34 
5.4 
Screen Failures .............................................................................................................. 34 
6 
STUDY INTERVENTION AND CONCOMITANT THERAPY ............................ 35 
6.1 
Study Intervention(s) Administered ............................................................................ 35 
6.2 
Preparation, Handling, Storage and Accountability ................................................. 35 
6.3 
Measures to Minimize Bias: Randomisation and Blinding ....................................... 36 
6.3.1 
Randomisation ............................................................................................ 36 
6.3.2 
Maintenance of Blinding ............................................................................ 36 
6.4 
Study Intervention Compliance ................................................................................... 36 
6.5 
Dose Modification ......................................................................................................... 36 
6.6 
Continued Access to Study Intervention after the End of the Study ....................... 36 
6.7 
Treatment of Overdose ................................................................................................. 36 
6.8 
Concomitant Therapy ................................................................................................... 37 
7 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ................................................................... 39 
7.1 
Discontinuation of Study Intervention ........................................................................ 39 

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7.1.1 
Temporary Discontinuation ........................................................................ 39 
7.2 
Participant Discontinuation/Withdrawal from the Study ........................................ 39 
7.3 
Lost to Follow-up .......................................................................................................... 39 
8 
STUDY ASSESSMENTS AND PROCEDURES ....................................................... 41 
8.1 
Demography .................................................................................................................. 41 
8.2 
Efficacy Assessments .................................................................................................... 41 
8.2.1 
Testosterone ................................................................................................. 41 
8.2.2 
Prostate-specific Antigen ............................................................................ 42 
8.3 
Safety Assessments ........................................................................................................ 42 
8.3.1 
Physical Examinations ............................................................................... 42 
8.3.2 
Vital Signs ................................................................................................... 42 
8.3.3 
Electrocardiograms ..................................................................................... 42 
8.3.4 
Magnetic Resonance Imaging Scan ........................................................... 42 
8.3.5 
Clinical Safety Laboratory Assessments .................................................... 43 
8.3.6 
Local Tolerance........................................................................................... 43 
8.4 
Adverse Events (AEs) and Serious Adverse Events (SAEs), and Other Safety 
Reporting ....................................................................................................................... 43 
8.4.1 
Time Period and Frequency for Collecting AE and SAE Information .... 44 
8.4.2 
Method of Detecting AEs and SAEs........................................................... 44 
8.4.3 
Follow-up of AEs and SAEs ....................................................................... 44 
8.4.4 
Regulatory Reporting Requirements for SAEs .......................................... 44 
8.4.5 
Pregnancy .................................................................................................... 44 
8.4.6 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs ......................................................................... 45 
8.4.7 
Adverse Events of Special Interest ............................................................. 45 
8.4.8 
Reporting of Study Intervention Errors Including Misuse/Abuse ............ 45 
8.5 
Pharmacokinetics .......................................................................................................... 45 
9 
STATISTICAL CONSIDERATIONS ........................................................................ 47 
9.1 
Statistical Hypotheses ................................................................................................... 47 
9.2 
Sample Size Determination .......................................................................................... 47 
9.3 
Analysis Sets .................................................................................................................. 47 
9.4 
Statistical Analyses ....................................................................................................... 48 
9.4.1 
General Considerations .............................................................................. 48 
9.4.1.1 
Reasons for Exclusion from the Analyses .................................................... 48 
9.4.1.2 
Significance Testing and Estimations .......................................................... 48 
9.4.1.3 
Statistical/Analytical Methods ..................................................................... 48 
9.4.2 
Analysis of Primary Endpoints ................................................................... 49 
9.4.3 
Analysis of Secondary Endpoints ............................................................... 49 
9.4.3.1 
Prostate-Specific Antigen............................................................................. 49 
9.4.3.2 
Pharmacokinetic and Pharmacodynamic Data Analysis ............................ 49 
9.4.4 
Analysis of Exploratory Endpoint .............................................................. 50 

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9.4.4.1 
Pharmacokinetic/Pharmacodynamic Relationship ...................................... 50 
9.4.5 
Safety Analyses ............................................................................................ 50 
9.4.6 
Subgroups Analyses .................................................................................... 51 
9.4.7 
Other Analyses ............................................................................................ 51 
9.5 
Interim Analyses ........................................................................................................... 51 
10 
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL 
CONSIDERATIONS .................................................................................................... 52 
10.1 Appendix: Regulatory, Ethical, and Study Oversight Considerations .................... 52 
10.1.1 
Regulatory and Ethical Considerations ..................................................... 52 
10.1.2 
Financial Disclosure ................................................................................... 52 
10.1.3 
Informed Consent Process .......................................................................... 52 
10.1.4 
Data Protection ........................................................................................... 53 
10.1.5 
Dissemination of Clinical Study Data ........................................................ 54 
10.1.6 
Data Quality Assurance .............................................................................. 54 
10.1.7 
Source Documents ...................................................................................... 55 
10.1.8 
Study and Site Start and Closure ................................................................ 55 
10.1.9 
Publication Policy ....................................................................................... 56 
10.2 Appendix: Clinical Laboratory Tests ......................................................................... 57 
10.3 Appendix: AEs and SAEs: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ............................................................................................ 58 
10.3.1 
Definition of AE .......................................................................................... 58 
10.3.2 
Definition of SAE ........................................................................................ 59 
10.3.3 
Recording and Follow-Up of AE and/or SAE ........................................... 60 
10.3.4 
Reporting of SAEs ....................................................................................... 61 
10.4 Appendix: American Joint Committee on Cancer (AJCC) TNM Staging System 
for Prostate Cancer ....................................................................................................... 63 
10.5 Appendix: ECOG Performance Scale ......................................................................... 64 
10.6 Appendix: Protocol Amendment History ................................................................... 65 
10.6.1 
Amendment 1: 11 November 2021 ............................................................. 65 
10.6.2 
Amendment 2: 07 April 2022 ...................................................................... 85 
11 
REFERENCES .............................................................................................................. 92 
 
LIST OF TABLES 
Table 1 
Schedule 
of 
Activities 
for 
All 
Participants 
Except 
the 
Pharmacokinetic/Pharmacodynamic Subset .................................................... 21 
Table 2 
Schedule of Assessments for the Pharmacokinetic/Pharmacodynamic 
Subset of Participants ......................................................................................... 23 
Table 3 
Study Risk Assessment ........................................................................................ 27 
Table 4 
Objectives and Endpoints ................................................................................... 29 
Table 5 
Study intervention administered ........................................................................ 35 

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Table 6 
Protocol-Required Safety Laboratory Tests ..................................................... 57 
 
LIST OF FIGURES 
Figure 1 
Study Schema ....................................................................................................... 19 
 

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LIST OF ABBREVIATIONS 
ABBREVIATION 
Wording Definition  
ADT 
Androgen deprivation therapy 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration versus time curve 
CA 
Competent authority 
CI 
Confidence interval 
Cmax 
Maximum concentration 
CRF/eCRF 
Case report form/electronic case report form 
CFR 
Code of Federal Regulations 
COVID-19 
Coronavirus disease 2019 
CRO 
Contract research organisation 
CSR 
Clinical study report 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
ECOG 
Eastern Cooperative Oncology Group 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good clinical practice 
GnRH 
Gonadotropin-releasing hormone 
Hb 
Haemoglobin 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
i.m. 
Intramuscular 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IVF 
In vitro fertilisation 
ITT 
Intention-to-treat 
LC-MS/MS 
Liquid chromatography tandem mass spectrometry 
LH 
Luteinising hormone 

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ABBREVIATION 
Wording Definition  
LHRH 
Luteinising hormone-releasing hormone 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCA 
Non-compartmental analysis  
NCI-CTCAE 
National Cancer Institute – Common Toxicity Criteria for Adverse 
Events 
NOS 
Not otherwise specified 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics  
PLGA 
Poly(1actide-CO-glycolide) 
PP 
Per Protocol 
PRAC 
Pharmacovigilance Risk Assessment Committee 
PSA 
Prostate specific antigen 
PT 
Preferred term 
SAE 
Serious adverse event 
SAS® 
Statistical Analysis Software 
SD 
Standard deviation 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected unexpected serious adverse reactions 
TEAE 
Treatment-emergent adverse event 
tcast 
Time to castration 
tmax 
Time to peak serum/plasma concentration 
TNM 
Tumour, lymph nodes, metastases 
ULN 
Upper limit of normal 
US 
United States of America 
WBC 
White blood cells 
WHO 
World Health Organisation 
WHODRUG 
WHO Drug Dictionary  
 

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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title:  
A multicentre, open-label, single-arm study to investigate the efficacy and safety of triptorelin 
pamoate 22.5 mg 6-month formulation in Chinese patients with locally advanced or metastatic 
prostate cancer  
 
Short Title:  
Effects of triptorelin pamoate 6-month when given to adult Chinese participants with advanced 
cancer in the prostate 
 
Rationale: 
The 6-month triptorelin formulation (22.5 mg) has been evaluated in a multicentre, 
non-comparative Phase III study in participants with advanced prostate cancer, conducted 
between July 2006 and August 2007 [Lundstrom 2009]. The results from the study have shown 
that the new triptorelin 6-month formulation (22.5 mg) rapidly induces and maintains castration 
in participants with locally advanced or metastatic prostate cancer. In the intention-to-treat 
(ITT) population, 97.5% (117/120) of participants were castrated (testosterone level <50 ng/dL) 
on Day 29, and 93.0% (107/115) of participants maintained castration from Week 8 (Day 57) 
to end of Week 48. The efficacy results of the 6-month formulation have been reviewed with 
those obtained in previous studies with the marketed triptorelin 1- and 3-month formulations. 
Results show that the rate of castration achieved with the 6-month formulation on Day 29, after 
the first triptorelin injection, was comparable to those with the 1-month and 3-month 
formulations [Breul 2017]. 
In terms of local tolerance at the injection site, intramuscular triptorelin injections were well 
tolerated as confirmed in the phase III study where injection site reactions were assessed by 
active questioning: 6.7% participants with injection-site reactions reported as adverse events 
(AEs), which is lower than for other 6-month gonadotropin-releasing hormone (GnRH) 
formulations [Lundstrom 2009]. In a pooled analysis, very few (<5%) local adverse reactions 
at the injection site have been reported in clinical studies with all triptorelin sustained-release 
formulations (1-, 3- and 6 month) [Breul 2017]. 
The advantage of the sustained-release 6-month triptorelin pamoate formulation is that the 
reduced frequency of injections will provide greater convenience to both the participants and 
the physician and it may also improve the participant acceptability and compliance with the 
injection schedule. 
The present study will assess the efficacy and safety of the sustained-release 6-month triptorelin 
pamoate formulation in Chinese participants with locally advanced or metastatic prostate cancer 
for confirming the registration of this product in China. At the same time, triptorelin 
pharmacokinetics (PK) and testosterone pharmacodynamics (PD) will be assessed in in this 
study population. 
 

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Overall Design: 
This is a prospective, interventional, multicentre, open-label phase IIIb, single-arm study with 
a treatment period of 24 weeks for each participant. A total of 195 Chinese adult participants 
with locally advanced or metastatic prostate cancer will be enrolled in the study. All enrolled 
participants will receive one intramuscular (i.m.) injection of the 6-month formulation 
containing 22.5 mg triptorelin pamoate on Day 1. 
 
Intervention Groups and Duration: 
Triptorelin pamoate 22.5 mg (6-month formulation), i.m. injection, single dose on Day 1. 
 
Visit Frequency:  
This study will consist of a 4-week screening period, a single open-label administration of the 
study intervention on Day 1. Following treatment, visits will occur on Day 2, Day 3, Day 5, 
Day 8, Day 15, Day 22 in a subset of 12 participants, and for all participants on Day 29, Day 57, 
Day 85, Day 113, Day 141 and Day 169.  
 
Study Participant Duration:  
Participants are expected to participate in this study for 24 weeks. 
 
Number of Participants: 
Approximately 195 participants (including a rich sampling pharmacokinetic/pharmacodynamic 
subset of 12 participants) are planned to be assigned to study intervention.  
 
Statistical Methods:  
Sample Size Determination 
The sample size was estimated based on data from the previous Study DEB-TRI6M-301, 97.5% 
of participants achieving castration on Day 29 and 93% of participants maintaining castration 
from Week 8 to Week 24. 
Sample size is calculated to fulfil the co-primary efficacy criteria of this study, which is to 
assess the proportion of participants achieving castrate levels of testosterone on Day 29 and the 
proportion of participants maintaining the castrate levels of serum testosterone from Week 8 to 
end of Week 24.  
For an exact binomial test of a proportion with a two-sided nominal significance level of 0.05 
and null proportion of 85%, a sample size of 165 participants has an exact power of 88.3% 
when the true proportion is 93% (of participants maintaining castration from Week 8 to 
Week 24). This sample size of 165 participants has a power >99.9% when the true proportion 
is 97.5% (of participants achieving castrate testosterone levels). Exact two-sided 95% CI for a 
binomial proportion was computed by statistical analysis software (SAS) using the exact 
binomial distributions. 
Assuming the dropout rate will be around 15%, a sample size of 195 participants with locally 
advanced or metastatic prostate cancer in total is planned for this study. 

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Primary Analysis
The analysis sets for the primary and secondary efficacy endpoints will be the full analysis set 
(FAS) and the per protocol (PP) set. 
Co-primary endpoints will be tabulated with two-sided 95% confidence interval (95% CI) using 
the Clopper-Pearson exact method.
Secondary Analyses
Prostate-specific antigen (PSA) percent change from pre-treatment Day 1 will be reported at 
Week 12 and Week 24, using descriptive statistics. The PK (triptorelin) and PD (testosterone) 
metrics will be reported as descriptive statistics.
For the analysis of safety, any participant who receives the single dose of triptorelin will be 
analysed (Safety population). The incidence of AEs as per National Cancer Institute – Common 
Toxicity Criteria (NCI-CTCAE) Version 5.0 grading will be summarised by System Organ 
Class (SOC), preferred term (PT) severity and relationship to study drug. Adverse events will 
be coded using Medical Dictionary of Drug Regulatory Activities (MedDRA) Version 24.1 (or 
higher if available) prior to analysis. Changes from baseline in clinical laboratory tests, physical 
examinations, electrocardiogram (ECG) and vital signs will be summarised using descriptive 
statistics.
The data will be summarised with the descriptive statistics (i.e. N, means, standard deviation, 
minimum, maximum, median) for the continuous variables and with counts and percentages for 
the categorical variables. In addition, for PK endpoints, the geometric mean, the standard 
deviation of the geometric mean, and geometric coefficient of variance% will be presented.
1.2
Schema
The study schema is shown in Figure 1.
Figure 1
Study Schema
PD=pharmacodynamic; PK=pharmacokinetic; Q4W=every 4 weeks

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1.3 
Schedule of Activities (SoA) 
The schedule of activities during the study is summarised for all participants in Table 1, except 
the PK/PD subset of 12 participants which is summarised in Table 2. 
If the Coronavirus Disease 2019 (COVID-19) pandemic prevents participants from coming to 
the site, participants can have their study visit assessments performed remotely as judged 
appropriate by the investigator. This must be discussed with the sponsor before being 
implemented. In such a case, the investigator will perform a telemedicine visit and will make 
every effort, where applicable, to contact the participant’s general practitioner or specialist 
physician to ensure all important medical information and safety event(s) occurring since the 
last visit are collected. Guidance on how to collect protocol-planned assessments will be 
provided to the investigator in a separate document. Such document will be filed in the trial 
master file. Independent ethics committees (IECs)/institutional review boards (IRBs) will be 
notified of the changes as applicable locally. Of note, as the adapted visit deviates from the 
regular protocol plan, the changes will be recorded as protocol deviations related to COVID-19.

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Table 1 
Schedule of Activities for All Participants Except the Pharmacokinetic/Pharmacodynamic Subset 
Procedure 
Screening 
 
Intervention Period 
EoS/EW 
End of Week 
- 
- 
Week 4 
Week 8 
Week 12 
Week 16 
Week 20 
Week 24  
Day 
D-28 to D-1 
D1 
D29 
D57 
D85 
D113 
D141 
D169 
Visit Window  
- 
- 
±3 days 
±3 days 
±3 days 
±3 days 
±3 days 
±3 days 
Informed consent 
X 
 
 
 
 
 
 
 
Eligibility  
X 
X 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
Medical and surgical history 
X 
 
 
 
 
 
 
 
Physical examination [f] 
X 
X [a] 
 
 
X 
 
 
X 
MRI scan [g] 
X 
 
 
 
 
 
 
 
Disease-specific medical history  
X 
 
 
 
 
 
 
 
Prior disease-specific treatment 
X 
 
 
 
 
 
 
 
Body weight 
X 
 
 
 
 
 
 
X 
Vital signs 
X 
X [a] 
X 
X 
X 
X 
X 
X 
12-lead electrocardiogram[b] 
X 
 
X 
 
 
 
 
X 
ECOG Score  
X 
 
 
 
 
 
 
 
Injection triptorelin 6M 
 
X 
 
 
 
 
 
 
Blood samples for triptorelin PK 
 
X [a] 
X 
X 
X 
X 
X 
X 
Blood sample for testosterone PD [h] 
X 
X [a, e] 
X 
X 
X 
X 
X 
X 
Blood samples for PSA [h] 
X 
X [a, e] 
 
 
X 
 
 
X 
Blood samples [c] laboratory safety tests 
X 
X [a, e] 
 
 
 
 
 
X 
Local tolerance [d] 
 
X 
 
 
 
 
 
 
Previous (excluding disease-specific) and concomitant 
medication  
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
6M=6-month formulation, AE=adverse event, ALT=alanine aminotransaminase, AST=aspartate aminotransaminase, CRF=case report form, D=day; ECG=electrocardiography; ECOG=Eastern Cooperative Oncology Group, 
EoS/EW=end of study/early withdrawal, Hb=haemoglobin, M1b=distant metastasis bone(s), MRI=magnetic resonance imaging; PD=pharmacodynamic, PK=pharmacokinetics, PSA=prostate-specific antigen, WBC=white 
blood cell. 

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a 
Assessment or blood sampling to be performed prior to study intervention injection. PK Predose sampling window (≤30 minutes). 
b 
ECG to be assessed as clinically indicated at any other time in the study as required. 
c 
Haematology (WBC, platelet count, Hb), Blood Chemistry (creatinine, glucose, ALT, AST, alkaline phosphatase, bilirubin (total and conjugated)) will be tested at the local  laboratory. Glucose: fasting levels in all 
participants at Screening visit, fasting levels on Days 1 and 169. Fasting is not necessary for diabetic participants. 
d  
Injection site to be specifically checked 2 hours ±15 minutes after injection for local reactions on Day 1. After Day 1, any local reaction AE to be collected on the CRF in the same manner as other AEs. 
e 
Measurement of testosterone, PSA and laboratory safety tests for analysis purposes only and not for eligibility. The screening testosterone, PSA and safety laboratory test results will be used for eligibility. 
f 
Complete physical examination to be performed (or brief physical examination based on investigator judgement). Participants, particularly those with M1b status, should be advised regarding clinical signs suggestive of 
spinal cord compression. 
g 
Scan for prostate gland or the whole body, only if necessary, based on investigator’s judgement. An MRI scan is not required if performed within 1 month of screening. 
h 
Testosterone and PSA testing will be performed at the central laboratory. 
See Appendix 10.5 for ECOG performance scale. 

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Table 2 
Schedule of Assessments for the Pharmacokinetic/Pharmacodynamic Subset of Participants 
Procedures 
Screening  
 
Intervention Period 
EoS/EW 
End of Week 
- 
- 
- 
- 
- 
- 
- 
- 
Week 
4 
Week 
8 
Week 
12 
Week 
16 
Week 
20 
Week  
24 
Day 
D-28 to  
D-1 
D1 
D2 
D3 
D5 
D8 
D15 
D22 
D29 
D57 
D85 
D113 
D141 
D169 
Visit Window 
 
 
 
 
 
 
 
 
 
±3 
days 
±3 
days 
±3 
days 
±3 
days 
±3 
days 
±3  
days 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and surgical history  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination [g] 
X 
X [a] 
 
 
 
 
 
 
 
 
X 
 
 
X 
MRI scan [h] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease-specific medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior disease-specific treatment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body weight 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital signs 
X 
X [a] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead electrocardiogram[b] 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
ECOG Score 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Injection triptorelin 6M 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sample for triptorelin PK 
 
X [c] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for testosterone PD [i] 
X 
X [a, f] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for PSA [i] 
X 
X [a, f] 
 
 
 
 
 
 
  
 
X 
 
 
X 
Blood samples for [d] laboratory safety 
tests 
X 
X [a, f] 
 
 
 
 
 
 
 
 
 
 
 
X 
Local tolerance [e] 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 

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Procedures 
Screening  
 
Intervention Period 
EoS/EW 
End of Week 
- 
- 
- 
- 
- 
- 
- 
- 
Week 
4 
Week 
8 
Week 
12 
Week 
16 
Week 
20 
Week  
24 
Day 
D-28 to  
D-1 
D1 
D2 
D3 
D5 
D8 
D15 
D22 
D29 
D57 
D85 
D113 
D141 
D169 
Visit Window 
 
 
 
 
 
 
 
 
 
±3 
days 
±3 
days 
±3 
days 
±3 
days 
±3 
days 
±3  
days 
Previous (excluding disease-specific) and 
concomitant medication  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
6M=6-month formulation, AE=adverse event, ALT=alanine aminotransaminase, AST=aspartate aminotransaminase, CRF=case report form, D=day; ECG=electrocardiography; 
ECOG=Eastern Cooperative Oncology Group, EoS/EW=end of study/early withdrawal; h=hours; Hb=haemoglobin, M1b=distant metastasis bone(s); MRI=magnetic resonance imaging; 
PD=pharmacodynamic, PK=pharmacokinetics, PSA=prostate-specific antigen, WBC=white blood cell. 
a 
Assessment or blood sampling to be performed prior to study intervention injection. 
b 
ECG to be assessed as clinically indicated at any other time in the study as required. 
c 
Sampling on Day 1. PK time sampling windows: 
• 
Pre-dose (≤30 mins) prior to study drug injection 
• 
1h, 2h, 3h post-dose ±5 mins 
• 
4h, 6h, 8h post-dose ±15 mins 
• 
12h post-dose ±30 mins 
• 
24h post-dose ±1 hour 
• 
48h post-dose ±2 hours 
• 
96h post-dose ±3 hours 
• 
168h post-dose ±4 hours 
• 
Day 15 (2 weeks post-dose) ±24 hours 
• 
Day 22 (3 weeks post-dose) ±24 hours 
• 
Day 29, 57, 85, 113, 141, 169 = clinic visit time windows (±3 days) 
d 
Haematology (WBC, platelet count, Hb), Blood Chemistry (creatinine, glucose, ALT, AST, alkaline phosphatase, bilirubin (total and conjugated) will be tested at the local laboratory. 
Glucose: Fasting levels in all participants at Screening visit, fasting levels on Days 1 and 169. Fasting is not necessary for diabetic participants. 
e  
Injection site to be specifically checked 2 hours ±15 minutes after injection for local reactions on Day 1. After Day 1 any local reaction AEs to be collected on the CRF in the same 
manner as other AEs. 
f 
Measurement of testosterone, PSA and laboratory safety tests for analysis purposes only and not for eligibility. The screening testosterone, PSA and safety laboratory test results will be 
used for eligibility. 
g 
Complete physical examination to be performed (or brief physical examination based on investigator judgement). Participants, particularly those with M1b status, should be advised 
regarding clinical signs suggestive of spinal cord compression. 
h 
Scan for prostate gland or the whole body, only if necessary, based on investigator’s judgement. An MRI scan is not required if performed within 1 month of screening. 
i 
Testosterone and PSA testing will be performed at the central laboratory. 
See Appendix 10.5 for ECOG performance scale. 

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2 
INTRODUCTION 
Triptorelin is an agonist analogue of natural GnRH. The principal modification consists of 
substitution of natural glycine in position 6 by a D-amino acid (D tryptophan). Clinical and 
animal studies have provided positive results of triptorelin’s action in hormone-dependent 
disorders such as prostate cancer, endometriosis, central precocious puberty, uterine 
fibromyomas, in vitro fertilisation and breast cancer. 
2.1 
Study Rationale 
Results from a global phase III study have shown that the new triptorelin 6-month formulation 
(22.5 mg) was well tolerated and rapidly induced and maintained castration in participants with 
locally advanced or metastatic prostate cancer [Lundstrom 2009]. 
The advantage of the sustained-release 6-month triptorelin pamoate formulation is that the 
reduced frequency of injections will provide greater convenience to both the patient and the 
physician and may also improve patient acceptability and compliance with the injection 
schedule. 
The present study will assess the efficacy and safety of the sustained-release 6-month triptorelin 
pamoate formulation in Chinese participants with locally advanced or metastatic prostate cancer 
for confirming the registration of this product in China. In addition, triptorelin 
pharmacokinetics (PK) and testosterone pharmacodynamics (PD) will be assessed in the study 
population. 
2.2 
Background 
Prostate cancer is one of the most commonly occurring malignancies in the male population 
and thus the second cause of death from cancer in men over 50 in the western world. In most 
patients, it is an androgen-dependent tumour at initial presentation. 
Growth of the prostatic tissue is regulated by a network of hormones in which androgens play 
a major role. Gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone 
releasing hormone (LHRH), released in a pulsatile manner by the hypothalamus, stimulates the 
pituitary to release in pulses the gonadotropins luteinizing hormone (LH) and follicle 
stimulating hormone (FSH). LH stimulates the production of testicular testosterone; however, 
approximately 5% of circulating testosterone is independently produced by the adrenal glands. 
FSH plays a role in the regulation of spermatogenesis. 
Since the pioneering studies of Huggins and Hodges [1941, 1941a] in the 1940's about the 
regulatory role played by the testicular androgens in the growth of prostate cancer cells, the 
mainstay of treatment for advanced prostate cancer was for decades androgen deprivation by 
bilateral orchiectomy and/or oestrogen therapy. The limitations of these therapeutic modalities 
led to the development of GnRH agonists, which have made medical castration the preferred 
option among many patients with metastatic disease [Filicori 1994]. The efficacy and safety of 
these agents is now well established, and GnRH agonists are not associated with an increased 
risk of cardiovascular disease. 
The therapeutic activity of the GnRH agonists is through pituitary down-regulation of their own 
receptors achieved by continuous and chronic administration, providing almost complete 
suppression of LH and FSH secretion leading to suppression of testicular function. 
Achievement of castration levels of testosterone is generally obtained around one month after 
start of therapy. Of note, long term endocrine status and evolution of advanced prostate cancer 
treated with GnRH agonists are similar to those observed after surgical castration [Parmar 1987, 
DeSy 1988, Botto 1987] but in contrast to surgical castration, treatment with GnRH agonists 
initially results in a markedly, albeit temporary (~2 weeks), increase of gonadal androgen 

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release (flare-up phenomenon). The initial rise in testosterone may cause a temporary 
worsening of symptoms including increase in bone pain within the first days of treatment; for 
these reasons, GnRH agonists are contraindicated for use in patients presenting metastases with 
neurologic symptomatology, or other possible life-threatening metastases. The most significant 
side effects - hot flushes, decreased libido and erectile dysfunction - are linked to the 
pharmacological effect (castrate levels of testosterone) and are usually relatively mild and 
reversible upon cessation of therapy. 
Since the discovery and synthesis of GnRH, many analogues of the native decapeptide have 
been synthesised in attempts to develop agonists with increased in vivo half-life and potency. 
As shown in the amino acid sequences below, the major structural difference between the native 
decapeptide and the triptorelin agonist is the substitution of a different D-amino acid at position 
six, which is the hinge between the two active portions of the peptide. However, triptorelin 
retains the parts of the native decapeptide responsible for its biological activity. 
 
 
 
GnRH has a L-glycine at position six, whereas triptorelin has a D-tryptophan. The substitution 
of the D-amino acid increases resistance to cleavage by proteolytic enzymes and increases 
biological potency relative to the native decapeptide [Barron 1982]. Triptorelin, like other 
GnRH agonists, has a short half-life in vivo (t½=5 h), therefore, sustained-release dosage forms 
have been developed by combining the peptide with a biocompatible and biodegradable 
copolymer (lactide-glycolide). By modifying the molar ratio of lactic acid to glycolic acid, the 
peptide is released continuously over periods ranging from 28 days (l-month formulation) to 
168 days (6-month formulation) following administration of a single intramuscular (i.m.) 
injection. 
The 6-month triptorelin formulation (22.5 mg) has been evaluated in a multicentre, 
non-comparative phase III study in participants with advanced prostate cancer, conducted 
between July 2006 and August 2007 [Lundstrom 2009]. The results from the study have shown 
that the new triptorelin 6-month formulation (22.5 mg) rapidly induces and maintains castration 
in participants with locally advanced or metastatic prostate cancer. In the intention-to-treat 
(ITT) population, 97.5% (117/120) of participants were castrated (testosterone level <50 ng/dL) 
on Day 29, and 93.0% (107/115) of participants maintained castration from Week 8 (Day 57) 
to end of Week 48. The efficacy results of the 6-month formulation have been reviewed with 
those obtained in previous studies with the marketed triptorelin 1- and 3-month formulations. 
Results show that the rate of castration achieved with the 6-month formulation on Day 29, after 
the first triptorelin injection, was comparable to those with the 1-month and 3-month 
formulations [Breul 2017]. 
In terms of local tolerance at the injection site, intramuscular triptorelin injections were well 
tolerated and in the phase III study where injection site reactions were assessed by active 
questioning: 6.7% participants with injection-site reactions reported as adverse events (AEs), 
which is lower than for other 6-month GnRH formulations [Lundstrom 2009]. In a pooled 
analysis, very few (<5%) local adverse reactions at the injection site have been 
reported in clinical studies with all triptorelin sustained-release formulations (1-, 3- and 
6-month) [Breul 2017]. 

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A more detailed description of the product, including further details on administration 
procedures and dosage are provided in Section 6. 
2.3 
Benefit/Risk Assessment 
Detailed information about the known and expected benefits and risks and reasonably expected 
AEs of triptorelin may be found in the IB. 
2.3.1 
Risk Assessment 
A risk assessment for this study is provided in Table 3. 
Table 3 
Study Risk Assessment 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Study Intervention: Triptorelin 
There is no major known 
nonclinical risk associated with 
the study intervention 
Clinical risks associated with the 
study intervention in may include:  
• 
hot flushes 
• 
erectile dysfunction 
• 
loss of libido 
• 
impaired physical activities 
• 
metabolic syndrome 
• 
cardiovascular events 
• 
anxiety/depression 
• 
decreased bone mineral 
density 
• 
risk of abortion or foetal 
abnormality [a] 
See Section 8.3 
See IB Section 6.6.1 
Participant selection: 
Participants with significant 
medical conditions and at high 
risk of presenting treatment related 
SAEs and high-grade toxicity will 
be excluded from the study. 
Participant monitoring: During 
the study, there will be close 
monitoring of the participants for 
safety including local tolerability 
(see Section 8.3.6) 
Withdrawal criteria: Participants 
who become at risk of 
unacceptable toxicity will be 
withdrawn from the study 
intervention. 
Study Procedures 
There are no specific risks related 
to the study design or procedures. 
All procedures requested for the 
study are commonly used in 
clinical practice and the design 
does not create any specific risk or 
delay possible therapeutic option 
for participants 
Not applicable 
IB=investigator’s brochure; SAE=serious adverse event 
a 
Pregnancy is not relevant in this study population. However, reproductive risks are listed for completeness for female 
partners of participants who may become pregnant. 
 
2.3.2 Benefit Assessment 
Based on the nonclinical and clinical data generated up to finalisation of the protocol, treatment 
with triptorelin 6-month formulation may maintain castrate levels of testosterone for a longer 
period, i.e. 6 months (24 weeks), thereby reducing the need for frequent injections, in Chinese 
participants with locally advanced or metastatic prostate cancer to a similar extent as in a 
previous global phase III study.  

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2.3.3 Overall Benefit: Risk Conclusion 
Taking into account the measures taken to minimise risk to participants, the potential risks 
identified in association with triptorelin are justified by the anticipated benefits that may be 
afforded to Chinese participants with locally advanced or metastatic prostate cancer. 

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ECG=electrocardiogram; PD=pharmacodynamics; PK=pharmacokinetics; PSA=prostate specific antigen; tcast=time to 
castration; TEAE=treatment-emergent adverse event; tmax=time to peak serum/plasma concentration 
Note: A list of laboratory parameters to be assessed during the study are presented in Appendix 10.2. 

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4 
STUDY DESIGN 
4.1 
Overall Design 
This is a prospective, interventional, multicentre, open-label phase IIIb, single-arm study with 
a treatment period of 24 weeks for each participant. A total of 195 Chinese adult participants 
with locally advanced or metastatic prostate cancer will be enrolled in the study. All enrolled 
participants will receive one i.m. injection of the 6-month formulation containing 22.5 mg 
triptorelin pamoate on Day 1.  
This study will consist of a 4-week screening period, during which participants with advanced 
or metastatic prostate cancer will be screened for eligibility. On Day 1, eligible participants will 
receive a single open-label administration of the study intervention. Following treatment on 
Day 1, visits will occur on Day 2, Day 3, Day 5, Day 8, Day 15, Day 22 in a subset of 
12 participants, and for all participants on Day 29, Day 57, Day 85, Day 113, Day 141 and 
Day 169. For more details on sampling schedule see the SoA (Table 1 and Table 2).  
The maximum duration of the study is approximately 30 months from screening to the last study 
visit. Participants who complete all scheduled visits will be considered to have completed the 
study. Participants who complete the study will have final procedures and assessments 
performed at the final visit (Day 169). Participants who withdraw from the study before the 
completion of the Day 169 evaluation period will have early discontinuation procedures and 
assessments performed at their final visit. 
The study design is illustrated in Figure 1. 
4.2 
Scientific Rationale for Study Design 
This single-arm, phase III study will investigate the efficacy, safety and PK/PD of triptorelin 
6-month formulation in Chinese adult males with locally advanced or metastatic prostate 
cancer. 
According to data from China National Cancer Registration Institute, prostate cancer has 
become the most common tumour in male urinary malignancies since 2008. The incidence rate 
was approximately 9.80/100,000 in 2014 and ranks the sixth common malignancy in male 
malignant tumours. The mortality of prostate cancer is 4.22/100,000, and it is the 9th common 
cause of death in all male malignancies. The staging varies widely between China and Western 
developed countries. In China, only 30% of newly diagnosed patients are clinically localised, 
and the rest are locally advanced or extensively metastatic disease, who have lost the chance of 
radical treatment with poor prognosis [National Health Commission China 2019]. This study 
will enrol adult Chinese men with advanced prostate cancer. 
The non-comparative, open-label clinical study design is acceptable as the efficacy of triptorelin 
will be assessed by the percentage of participants achieving castrate levels of serum testosterone 
(defined as <50 ng/dL or 1.735 nmol/L) on Day 29 and maintaining castrate levels of serum 
testosterone from Week 8 to Week 24 (co-primary endpoints). Studies conducted in Western 
countries have shown that the rate of castration achieved with the 6-month formulation on 
Day 29, after the first triptorelin injection, was comparable to those with the 1-month and 
3-month formulations [Breul 2017]. No studies have evaluated the 6-month triptorelin 
formulation in Chinese men with locally advanced or metastatic prostate cancer, thus the 
outcomes of this study intend to fulfil an unmet need and provide treatment convivence for the 
patient and physician. 
This study will evaluate the PK/PD profile of triptorelin 6-month formulation in this study 
population. The blood sample collection scheme was designed to collect the minimum number 
of blood samples to help provide useful PK/PD information of study treatment in Chinese men 
with locally advanced or metastatic prostate cancer. 

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4.3 
Justification for Dose 
For this intervention, the term “dose” refers to the i.m. injection of triptorelin 22.5 mg created 
to guarantee the release of a monthly dose of 3.75 mg over a 169-day period. In addition, results 
from a phase III study have shown the 6-month triptorelin 22.5 mg formulation to induce and 
maintain castration in participants with locally advanced or metastatic prostate cancer, as well 
as demonstrate a good safety profile [Lundstrom 2009]. 
4.4 
End of Study Definition 
The end of the study (EoS) is defined as the date of the last visit of the last participant in the 
study as shown in the SoA (Table 1 and Table 2).  
The overall duration of the study (from first participant in, to last participant out) will be 
approximately 30 months. The study will be considered to have ended after the last participant 
has completed the last visit (at Week 24) in the study. 
A participant is considered to have completed the study if they have completed all phases of 
the study including the last visit.  
Criteria for study intervention discontinuation and participant discontinuation/withdrawal from 
the study are described in Section 7.1 and Section 7.2, respectively. Loss to follow-up is 
described in Section 7.3. 

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5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known 
as protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Participant is capable of giving signed informed consent as described in Appendix 10.1 
which includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
2. Participant must be over 18 years of age, at the time of signing the informed consent. 
3. Has a histologically or cytologically confirmed adenocarcinoma, locally advanced or 
metastatic prostate cancer, which is staged T3-4NxM0 or TxN1M0 or TxNxM1 according 
to the TNM classification (Appendix 10.4). Or participant has PSA recurrence after 
curative treatment and be a candidate for androgen deprivation therapy (ADT). 
(Note: PSA recurrence after radical prostatectomy: PSA ≥0.2 ng/mL and rising, 
confirmed on a repeat test; PSA recurrence after radiation therapy: PSA increased 
2 ng/mL than the lowest level.) 
4. Has serum testosterone level >150 ng/dL (> 5.2 nmol/L). 
5. Has expected survival time ≥12 months according to the investigator’s assessment. 
6. Has Eastern Cooperative Oncology Group (ECOG) performance status score ≤1 (see 
Appendix 10.5). 
7. Has absence of another malignancy, other than local dermatological, for the previous 
5 years. 
8. Participant is male. 
9. Male participants must agree that, if their partner is at risk of becoming pregnant, they 
will use an effective method of contraception. The participant must agree to use the 
contraception during the whole period of the study and for 9 months after the last dose 
of study intervention. 
5.2 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply:  
Medical conditions 
1. Risk of a serious complication in the case of tumour flare (known or suspicion of 
vertebral metastases threatening spinal cord compression or significant obstructive 
uropathy). 
2. Presence of another neoplastic lesion or brain metastases. 
3a. Previous history of QT prolongation or concomitant use of medicinal products known 
to prolong the QT interval or with a known risk of torsades de pointes. 
4a. Metastatic hormone-sensitive prostate cancer with high tumour burden.  
(Note: high tumour burden: presence of visceral metastases and/or at least four bone 
lesions with at least one lesion outside the vertebral column and/or pelvis per 
CHAARTED study (Kyriakopoulos 2018). 
5. Metastatic castration-resistant prostate cancer. 
Prior/concomitant therapy 
6. Previous surgical castration. 

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7a. Previous hormone therapy (including abiraterone) for prostate cancer within 6 months 
prior to study screening. 
8a. Previous cytotoxic chemotherapy treatment within 6 months prior to study screening. 
9a. Use of finasteride or dutasteride within 2 months prior to study screening. 
10. Previous hypophysectomy or adrenalectomy. 
11a. Any current use or use within 6 months prior to treatment start of medications which 
are known to affect the metabolism and/or secretion of androgenic hormones: 
ketoconazole, aminoglutethimide, oestrogens and antiandrogens.  
Note: antiandrogen: enzalutamide, apalutamide or darolutamide is allowed (if required 
per investigator’s clinical judgement) due to no interference on the metabolism and/or 
secretion of androgenic hormones. 
12a. Current use of systemic or inhaled corticosteroids (topical application permitted). 
13. Any previous use of traditional Chinese medicine or herbal products within 1 month 
prior to study screening or planned use during the study of products, which are known 
to have cytotoxic effect or affect the metabolism and/or secretion of androgenic 
hormones. 
Prior/concurrent clinical study experience 
14a. Participation in another study with an investigational drug or treatment within 3 months 
prior to study screening or within 5 drug half-lives of the investigational drug 
(whichever is the longer). 
Diagnostic assessments 
15. Severe kidney or liver impairment (creatinine >2 x upper limit of normal (ULN), 
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 x ULN). 
Other exclusions 
16. Any concomitant disorder or resulting therapy that is likely to interfere with participant 
compliance, the i.m. administration of the drug or with the study in the opinion of the 
investigator. 
17. Known hypersensitivity to triptorelin or any of its excipients, GnRH, other GnRH 
agonist/analogues. 
18. Known active use of recreational drug or alcohol dependence in the opinion of the 
investigator. 
5.3 
Lifestyle Considerations 
Participants will be advised to avoid chronic alcohol use and smoking during the study. 
5.4 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical study is 
not subsequently entered in the study. A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure participants to meet the Consolidated Standards 
of Reporting Trials (CONSORT) publishing requirements and to respond to queries from 
regulatory authorities. Minimal information includes date of informed consent, demography, 
reason for screen failure, eligibility criteria and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this study (screen failure) will not 
be rescreened. 

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6 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol. 
6.1 
Study Intervention(s) Administered 
Study intervention is described in Table 5. 
Table 5 
Study intervention administered  
Intervention Name 
Triptorelin pamoate (embonate) salt 
Intervention Description 
A PR formulation of triptorelin pamoate 6-month formulation 
in D,L-lactide-co-glycolide polymers for single i.m injection 
Type  
Drug  
Dose Formulation 
A yellow freeze-dried cake or powder supplied in a single 
6 mL glass vial 
Unit Dose Strength(s) 
22.5 mg (with release of a monthly dose of 3.75 mg over a 
169-day period) 
Dosage Level(s) 
Single dose delivered on Day 1 
Route of Administration 
i.m. injection 
Use 
Experimental 
IMP and NIMP/AxMP 
IMP  
Sourcing 
Manufactured by Debiopharm and provided centrally by the 
sponsor 
Packaging and Labelling 
Study intervention will be provided in a box containing one 
vial, one ampoule and one blister containing one injection 
syringe and two injection needles. Each box will be labelled 
as required per country requirement. 
Storage requirements 
To be stored in the outer carton at a temperature below 25°C 
in a dry place, protected from freezing 
Current Name 
Diphereline® 
i.m.=intramuscular; IMP=investigational medicinal product; NIMP=non-investigational medicinal product; 
AxMP=auxiliary medicinal product; PR=prolonged release 
 
6.2 
Preparation, Handling, Storage and Accountability 
The investigator or an approved representative (e.g. pharmacist) will ensure that triptorelin is 
reconstituted and dispensed by a member of staff specifically authorised by the Investigator and 
trained for the IMP reconstitution and administration. 
The suspension for injection must be reconstituted using an aseptic technique and only using 
the ampoule of solvent for injection. 
The instructions for reconstitution hereafter and in the leaflet provided with triptorelin must be 
strictly followed. 
The solvent should be drawn into the syringe provided using the reconstitution needle (20 G, 
without safety device) and transferred to the vial containing the powder. The suspension should 
be reconstituted by swirling the vial gently from side to side for long enough until a 
homogeneous, milky suspension is formed. Do not invert the vial. 
It is important to check there is no unsuspended powder in the vial. The suspension obtained 
should then be drawn back into the syringe, without inverting the vial. The reconstitution needle 
should then be changed, and the injection needle (20 G, without safety device) used to 
administer the product. 
As the product is a suspension, the injection should be administered for a single use immediately 
after reconstitution to prevent precipitation. 

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• 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
• 
Only participants screened in the study and who meet the eligibility criteria may receive 
study intervention and only authorised site staff may supply or administer study 
intervention. All study intervention must be stored in a secure, environmentally 
controlled and monitored (manual or automated) area in accordance with the labelled 
storage conditions with access limited to the investigator and authorised site staff. 
• 
The investigator, institution or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(i.e. receipt, reconciliation and final disposition records). 
• 
The sponsor will provide guidance on the destruction of unused study intervention. If 
destruction is authorised to take place at the investigational site, the investigator must 
ensure that the materials are destroyed in compliance with applicable environmental 
regulations, institutional policy and any special instructions provided by the sponsor. All 
destruction must be adequately documented. 
Further guidance and information for the receipt, preparation, management and disposal/return 
of the study intervention are provided in the “Investigational Medicinal Product Handling 
Manual”. 
6.3 
Measures to Minimize Bias: Randomisation and Blinding 
6.3.1 
Randomisation 
This is a non-randomised, open-label study. 
6.3.2 
Maintenance of Blinding 
This is an open-label study therefore no procedures for blinding are applicable. 
6.4 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the site will be recorded in the source documents and in the electronic case 
report form (eCRF). The dose of study intervention and study participant identification will be 
confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study intervention.  
6.5 
Dose Modification 
Not applicable. No dose modifications are to be performed in the study. 
6.6 
Continued Access to Study Intervention after the End of the Study 
The participants will not receive any additional study intervention following the end of the 
study. 
6.7 
Treatment of Overdose 
The pharmaceutical properties of triptorelin 6-month formulation and its mode of 
administration make accidental or intentional overdose unlikely. There is no experience of 
overdose from clinical studies (for more information see the summary of product 
characteristics). If overdose occurs, this should be managed symptomatically. 
In the event of an overdose, the investigator should: 
• 
Contact the medical monitor immediately. 

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• 
Closely monitor the participant for any AE/SAE and laboratory abnormalities (at least 
up to the Week 24 visit). 
• 
Document the quantity of the excess dose as well as the duration of the overdose. See 
Section 10.3.1 for reporting requirements concerning overdose. 
6.8 
Concomitant Therapy 
Any medication (excluding prior disease-specific medications) or vaccine (including over the 
counter prescription medicines, recreational drugs, vitamins, and/or herbal supplements) that 
the participant had received within 2 months before triptorelin administration or receives during 
the study must be recorded on the eCRF along with: 
• 
Generic or trade name 
• 
Reason for use 
• 
Dates of administration including start and end dates 
• 
Dosage information including dose, frequency and route of administration 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
The following concomitant medications are not permitted during this study: 
• 
Any treatment or procedure with a specific or potential effect on androgenic hormones 
be administered concomitantly to the study drug (will be considered as a protocol 
violation). Per investigator’s clinical judgement, suggest offering short-term 
administration of an older generation androgen receptor antagonist to M1 participants 
starting study intervention to reduce the risk of the ‘flare-up’ phenomenon. 
• 
Any medication which raises prolactin levels and those affecting pituitary secretion of 
gonadotropins 
• 
All drugs mentioned as prohibited in the exclusion criteria: 
o Finasteride or dutasteride. 
o Medications which are known to affect the metabolism and/or secretion of 
androgenic hormones: ketoconazole, aminoglutethimide, oestrogens. 
o Systemic or inhaled corticosteroids (topical application permitted). 
o Cytotoxic chemotherapy, abiraterone. 
o Any traditional Chinese medicine or herbal products previous used within 1 month 
prior to study start or plan to be used during the study, which are known to have 
cytotoxic effect or affect the metabolism and/or secretion of androgenic hormones. 
o Concomitant use of medications known to prolong QT interval should not be given 
(class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, 
dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, 
antipsychotics). 
The following concomitant medications are permitted during this study, but they must be 
monitored closely, and every effort should be made to keep their dose and dose regimen 
constant throughout the course of the study: 
• 
Analgesics: are allowed when necessary for pain relief. 
• 
Anticonvulsants (e.g phenobarbital): long-term therapy may have additional risk for 
osteoporosis. 
• 
Other medications: any treatment which is considered necessary for the participant’s 
welfare, may be given at the discretion of the investigator. 

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Other procedures: any diagnostic, therapeutic or surgical procedure performed during the study 
period should be recorded, including the date, indication, description of the procedure(s), and 
any clinical findings. 

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7 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific sites or of the study as a whole are detailed in Section 10.1.8. 
7.1 
Discontinuation of Study Intervention 
In this study, there will only be one treatment cycle administered on Day 1 of the study, thus 
discontinuation of the study intervention is not applicable (i.e. no repeat cycles). In the event a 
participant is enrolled, but does not receive study intervention, the participant will not remain 
in the study and EoS/EW assessment will not be performed. Only the reason for discontinuation 
will be collected. 
If participants are lost to follow-up, publicly available information should be used to determine 
vital status only as appropriately directed in accordance with local law. 
7.1.1 
Temporary Discontinuation 
In case of suspected or confirmed COVID-19 (SARS-CoV-2) infection, the intervention 
administration may be temporarily postponed depending on the participant clinical 
presentation. In some cases, the investigator may request a participant be retested before the 
intervention administration.  
7.2 
Participant Discontinuation/Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioural or 
compliance reasons.  
• 
At the time of discontinuing from the study, an early discontinuation visit should be 
conducted, as shown in the SoA. See SoA for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
• 
The reason for discontinuation will be recorded in the eCRF. 
• 
If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such withdrawal of consent. 
• 
If the participant withdraws consent for any further contact, the investigator will explain 
in the medical records that the participant was also withdrawn from study procedures. 
This information must be entered in the eCRF.  
• 
If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records. 
• 
A participant will be withdrawn from the study if they have inadequate testosterone 
suppression (defined as >50 ng/dL detected at least 30 days after administration of study 
intervention and on two consecutive measurements at least 2 weeks apart, at either a 
scheduled or unscheduled study visit). 
7.3 
Lost to Follow-up 
A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as soon 
as possible. The site should counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study. 

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• 
Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, three telephone calls 
and, if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  
• 
Site personnel will attempt to collect the vital status of the participant within legal and 
ethical boundaries for all participants enrolled, including those who did not receive study 
intervention. Public sources may be searched for vital status information. If vital status 
is determined as deceased, this will be documented, and the participant will not be 
considered lost to follow-up. Sponsor personnel will not be involved in any attempts to 
collect vital status information.  

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8 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarised in the SoA (Table 1 and Table 2). 
Protocol waivers and exemptions are not allowed. 
• 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention. 
• 
Adherence to the study design requirements, including those specified in the SoA (Table 
1 and Table 2), is essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
• 
Procedures conducted as part of the participant’s routine clinical management (e.g. blood 
count) and obtained before signing of the ICF may be utilised for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the timeframe defined in the SoA (Table 1 and Table 2) 
• 
The maximum amount of blood collected from each participant over the duration of the 
study, including any extra assessments that may be required, will not exceed 95 mL for 
the PK/PD subset of participants and 60 mL for all other participants. Blood sampling 
should be taken at the same time of day during different visits. 
• 
Repeat or unscheduled samples may be taken for safety reasons or in case of technical 
issues with the samples. 
8.1 
Demography 
Age, sex and, according to individual country regulations/requirements and if authorised in the 
country, race/ethnicity will be collected.  
8.2 
Efficacy Assessments 
Efficacy will be assessed in this study using the surrogate PD markers for testosterone and PSA 
concentrations. 
Approximately 26 mL of blood will be collected from all participants, and approximately 
38 mL of blood from the PK/PD subset participants, for measurement of testosterone and PSA. 
Serum samples used to evaluate testosterone and PSA will be divided into two aliquots (one 
primary and one back-up). 
Further instructions for the collection, handling and shipment of biological samples will be 
provided by the sponsor and described in the study Laboratory Manual. 
8.2.1 
Testosterone 
Testosterone will be assessed by a third-party vendor, as described in the Laboratory Manual. 
Serum will be analysed to determine concentrations of testosterone using a validated, specific 
and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. 
Blood samples for the determination of testosterone serum concentrations will be collected at 
the timepoints indicated in the SoA (Table 1 (all participants) and Table 2 (for the subset of 
12 participants)). 
Residual serum samples remaining from the analysis may also be retained by the sponsor for 
up to 5 years after completion of the study. This could include using leftover serum for long-
term stability or reproducibility assessments. 

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Surplus serum samples can only be used in China. Surplus serum samples will be managed 
anonymously and will not be identifiable. 
8.2.2 
Prostate-specific Antigen 
PSA will be assessed centrally, as described in the study Laboratory Manual. 
Blood samples for the determination of PSA plasma concentrations will be collected at the 
timepoints indicated in Table 1 (all participants) and Table 2 (for the subset of 12 participants).  
8.3 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. Evaluations obtained as 
part of routine medical care and performed during the screening period may be used in place of 
the study specific evaluations. Participants will acknowledge and agree to the possible use of 
this information for the study by giving informed consent. 
8.3.1 
Physical Examinations 
A complete physical examination will include, at a minimum, assessments of the skin, and 
cardiovascular, respiratory, gastrointestinal and neurological systems. Height and weight will 
also be measured and recorded. Body weight will be measured in underwear and without shoes. 
A brief physical examination will include, at a minimum, assessments of the lungs, 
cardiovascular system, abdomen (liver and spleen). 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Any clinically significant physical examination findings (abnormalities) observed during the 
study will be reported as AEs. Any physical examination findings (abnormalities) persisting at 
the end of the study will be followed by the investigator until resolution or until clinically stable. 
In addition, participants, particularly those with M1b status, should be advised regarding 
clinical signs suggestive of spinal cord compression. 
8.3.2 
Vital Signs 
Blood pressure, temperature, respiratory rate and heart rate will be assessed as outlined in the 
SoA (Section 1.3) with an automated device (if possible) so that measurements are independent 
of the observer. Blood pressure and heart rate will be recorded after 5 minutes rest in supine or 
seated position. Absolute values and change from Baseline will be analysed. Any clinically 
significant vital signs will be recorded as AEs. 
8.3.3 
Electrocardiograms 
A 12-lead ECG analysis will be included as a safety evaluation/endpoint in this study at 
timepoints described in Table 1 and Table 2. 
A single 12-lead ECG will be recorded so that the different ECG intervals (RR, PR, QRS, QT, 
QTcF) can be measured automatically. The ECG will be recorded with the participant in supine 
position after five minutes of rest until four regular consecutive complexes are available.  
Any clinically significant abnormalities will be recorded as AEs. 
8.3.4 
Magnetic Resonance Imaging Scan 
A magnetic resonance imaging (MRI) scan for prostate gland or the whole body, only if 
necessary (based on investigator’s judgement), will be performed as described in the SoA 
(Table 1 and Table 2) to confirm disease stage prior to study entry. An MRI scan is not required, 
if performed within 1 month of study screening.  

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8.3.5 
Clinical Safety Laboratory Assessments 
• 
All clinical laboratory safety tests (haematology and blood biochemistry) will be 
assessed locally. 
• 
See Appendix 10.2 for the list of clinical laboratory tests to be performed and to the SoA 
(Section 1.3) for the timing and frequency. 
• 
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study as an AE. The laboratory reports 
must be filed with the source documents.  
• 
Abnormal laboratory findings associated with the underlying disease, are not considered 
clinically significant unless judged by the investigator to be more severe than expected 
for the participant's condition. 
• 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 168 days after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 
• 
If clinically significant values do not return to normal/baseline within a period of 
time judged reasonable by the investigator, the aetiology should be identified, and 
the sponsor notified. 
• 
All protocol-required laboratory tests, as defined in Appendix 10.2, must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3). 
• 
If laboratory values from non-protocol specified laboratory tests performed at the 
study site laboratory require a change in participant management or are considered 
clinically significant by the investigator (e.g. SAE or AE or dose modification), 
then the results must be recorded in the eCRF. 
Haematology blood samples (2 mL) will be collected in a potassium ethylenediaminetetraacetic 
acid tube. Blood biochemistry samples (3 mL) will be collected in an activator gel tube. 
8.3.6 
Local Tolerance 
Local tolerance will be assessed 2 hours (±15 minutes) after injection. After the single injection 
of 6-month formulation triptorelin, the injection site will be examined by a physician or Medical 
Research Associate and assessed for characteristics such as but not limited to tenderness, 
redness, bruising, erythema, swelling, rash, pain, itching, induration, haematoma, ulceration or 
necrosis. If present, the extent of erythema, haematoma, rash, ulceration or necrosis will be 
described and assessed quantitatively; this will at least include measurement of maximum 
length and maximum width. If any reactions meet the definition of a treatment-emergent 
adverse event (TEAE), they are to be reported in the eCRF as such (see Section 9.4.5). 
8.4 
Adverse Events (AEs) and Serious Adverse Events (SAEs), and Other Safety 
Reporting 
The definitions of AEs and serious adverse events (SAEs) can be found in Appendix 10.3. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up all AEs or SAEs, considered related to the study intervention or study procedures (see 
Section 7). 

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The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 10.3. 
8.4.1 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF until the EoS at the time points 
specified in the SoA (Section 1.3). 
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the AE section of the case report form. 
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours of awareness of the event, as indicated in 
Appendix  10.3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the investigator learns of any SAE, including a death, at 
any time after a participant has been discharged from the study, and he/she considers the event 
to be reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor. 
8.4.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.4.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs/SAEs will be followed until resolution or 
stabilisation or the participant is lost to follow-up (as defined in Section 7.3). Further 
information on follow-up procedures is provided in Appendix 10.3. 
8.4.4 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety 
of a study intervention under clinical investigation are met. 
• 
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
• 
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g. summary or listing of SAEs) from the sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, 
if appropriate according to local requirements. 
• 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor’s policy and 
forwarded to investigators as necessary. 
8.4.5 
Pregnancy 
All participants in this study are male. The investigator must instruct all male participants to 
inform the investigator immediately should their partner become pregnant. 

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• 
Details of all pregnancies in female partners of male participants will be collected from 
the signing of the ICF and until up to 9 months after the participants last dose of study 
intervention.  
• 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate forms (Pregnancy Notification Form– paper form) and submit it to the 
sponsor within 24 hours of learning of the female partner of male participant becoming 
pregnant (after obtaining the necessary signed informed consent from the female 
partner). 
• 
Any pregnancy complication or elective termination of a pregnancy for medical reasons 
will be reported as an AE or SAE. 
• 
Abnormal pregnancy outcomes (e.g. spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported as 
such. 
• 
The participant’s pregnant female partner will be followed to determine the outcome of 
the pregnancy unless consent is not given/withdrawn. The investigator will collect 
follow-up information on the participant’s pregnant female partner and the neonate and 
the information will be forwarded to the sponsor. 
• 
Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.4.4. While the investigator is not obligated to actively seek this information in 
a former study participant’s pregnant female partner, he or she may learn of an SAE 
through spontaneous reporting. 
8.4.6 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. 
8.4.7 
Adverse Events of Special Interest  
Not applicable. 
8.4.8 
Reporting of Study Intervention Errors Including Misuse/Abuse 
• 
Medication errors are unintentional errors in the prescribing, storing, dispensing, 
preparing or administration of a study intervention (medicinal product) while under the 
control of a healthcare professional, participant or consumer. 
• 
Misuse refers to situations where the study intervention is intentionally and 
inappropriately used not in accordance with the protocol. 
• 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
• 
Study intervention errors and uses outside of what is foreseen in the protocol will be 
recorded in the eCRF irrespective of whether associated with an AE/SAE or not. It will 
also be documented in the AE section of the eCRF if associated with an AE. It will be 
reported in the safety database only if associated with an SAE. 
8.5 
Pharmacokinetics 
• 
Approximately 14 mL of blood will be collected from all participants, and approximately 
40 mL of blood from the PK/PD subset participants, for measurement of plasma 
concentrations of triptorelin 6-month formulation as specified in the SoA (Section 1.3) 

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• 
Instructions for the collection, handling and shipment of biological samples will be 
provided by the sponsor and described in the study laboratory manual. The accurate date 
and time (24-hour clock time) of each sample collection must be recorded. 
• 
Plasma samples will be used to evaluate the PK of triptorelin 6-month formulation. Each 
plasma sample will be divided into two aliquots (one primary and one backup). Samples 
collected for analyses of triptorelin concentration may also be used to evaluate safety or 
efficacy aspects related to concerns arising during or after the study. 
• 
During the study, the nominal sample collection times may be changed, but the total 
number of samples will not increase. The exact dates and times of blood sample 
collection and study drug administration must be recorded in the eCRF. 
• 
On predetermined dates, plasma samples will be shipped to the bioanalytical service 
provider under frozen conditions. For security reasons, the back-up aliquots will not be 
shipped until the primary aliquots have arrived. Upon receipt at the bioanalytical service 
provider, samples will be checked and stored until analysis.  
• 
Plasma will be analysed to determine concentrations of triptorelin using a validated, 
specific and sensitive LC-MS/MS methods. 
• 
Surplus plasma samples will be used in China and will not be shipped outside China. 
Surplus plasma samples will be managed anonymously and will not be identifiable. 
• 
Residual plasma samples remaining from the analyses may also be retained by the 
sponsor for up to 5 years after completion of the study. This could include using leftover 
plasma for long-term stability or reproducibility assessments. 
 

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9 
STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
No statistical hypotheses are planned for this study. 
9.2 
Sample Size Determination 
The sample size was estimated based on data from the previous Study DEB-TRI6M-301, 97.5% 
of participants achieving castration and 93% of participants maintaining castration from 
Week 8 to Week 24. 
Sample size is calculated to fulfil the co-primary efficacy criteria of this study, which is to 
assess the proportion of participants achieving castrate levels of testosterone on Day 29 and the 
proportion of participants maintaining the castrate levels of serum testosterone from Week 8 to 
end of Week 24. A total of 195 participants with advanced prostate cancer will be enrolled to 
receive the triptorelin pamoate 22.5 mg 6-month formulation.  
For an exact binomial test of a proportion with a two-sided nominal significance level of 0.05 
and null proportion of 85%, a sample size of 165 participants has an exact power of 88.3% 
when the true proportion is 93% (of participants maintaining castration from Week 8 to 
Week 24). This sample size of 165 participants has a power >99.9% when the true proportion 
is 97.5% (of participants achieving castrate testosterone levels). Exact two-sided 95% 
confidence interval (CI) for a binomial proportion was computed by SAS using the exact 
binomial distributions. 
Assuming the dropout rate will be around 15%, a sample size of 195 participants in total is 
planned for this study. 
9.3 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
Participant Analysis Set 
Description 
Screened  
All participants screened (i.e. who signed the informed consent). 
Safety Set 
The safety set will contain all participants who receive the single dose of 
study intervention.  
Full Analysis Set  
The FAS will contain all treated participants who complete the study or is a 
treatment failure. 
Completing the study is defined as having serum testosterone measurement 
at baseline, Day 29 and Day 169. Treatment failure is defined as escaping 
castration (testosterone level ≥50 ng/dL) at any assessments on and after 
Day 29 during the study, or premature discontinuation from the intervention 
period due to drug-related reasons (adverse event or death). 
Per Protocol Set 
All participants in the FAS who have no impacting major protocol 
deviations (i.e. that could potentially affect the primary efficacy endpoint 
outcome for the participant) as described in the protocol deviations 
document. 
Rich PK Analysis set (for 
non-compartmental analysis) 
Participants in the PK/PD subset who receive one dose of study intervention, 
have no major protocol deviations affecting the PK variables, and who have 
a sufficient number of plasma concentrations to estimate the main PK 
parameters (maximum observed plasma drug concentration (Cmax), time to 
maximum observed drug concentration (tmax) and area under the plasma 
concentration time curve (AUC)) 
Population PK Analysis Set 
All participants who received one dose of triptorelin and who have at least 
one triptorelin plasma concentration and no major protocol deviations 
affecting PK variables. 

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Participant Analysis Set 
Description 
Rich PD Analysis Set 
all participants in the PK/PD subset who have a sufficient number of PD 
(testosterone) measurements to estimate the main PD parameters (maximum 
observed concentration (Cmax), time to maximum observed concentration 
(tmax) and time to castration (tcast)) 
FAS=full analysis set; PD=pharmacodynamic PK=pharmacokinetic 
 
The efficacy analysis for the primary and secondary efficacy endpoints will be presented for 
the full analysis set (FAS) and per protocol (PP) population. The analysis of the safety data will 
be performed based on the safety set and analysis of PK and PD in the relevant PK analysis set  
9.4 
Statistical Analyses 
The statistical analysis plan (SAP) will be finalised before the first participant enters the study 
and it will include a more technical and detailed description of the statistical analyses described 
in this section. This section is a summary of the planned statistical analyses of the most 
important endpoints including primary and key secondary endpoints. 
Other endpoints as well as demographic, baseline characteristics and disposition will be detailed 
in the SAP. 
Statistical evaluation will be performed using Statistical Analysis System (SAS®) Version 9.4 
(or higher if available). 
9.4.1 
General Considerations 
9.4.1.1 
Reasons for Exclusion from the Analyses 
Any major protocol deviation will be described and listed and its impact on inclusion of any 
participant in each analysis population will be specified. The final list of protocol deviations 
impacting each analysis population will be reviewed prior to database lock. The list may be 
updated, up to the point of database lock, to include any additional major protocol deviations 
impacting inclusion in the PP set. 
9.4.1.2 
Significance Testing and Estimations 
As this is a descriptive safety and efficacy study, no formal statistical testing will be carried 
out. 
9.4.1.3 
Statistical/Analytical Methods 
Statistical analyses will be performed by an external CRO, managed by the sponsor’s Biometry 
department. 
Demographic and Other Baseline Characteristics 
Descriptive summary statistics (n, mean, standard deviation (SD), median, minimum, 
maximum) or frequency counts of demographic and baseline data (medical history, 
concomitant disease (predosing AEs and ongoing medical history, prior medications and 
therapies, etc.) will be presented for the FAS, PP and safety sets. 
Participant Disposition and Withdrawals 
The numbers and percentages of participants screened and included in each of the populations 
will be tabulated overall and by centre. The reasons for participant exclusions from each of the 
populations will also be tabulated. Primary reasons for discontinuation of study will be 
tabulated. 
Adjustment for Country/Centre Effects 
Descriptive analysis will be carried out to evaluate any possible centre effect. 

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9.4.2 
Analysis of Primary Endpoints 
The co-primary efficacy variables are 
• 
percentage of participants achieving castrate levels of serum testosterone (<50 ng/dL or 
1.735 nmol/L) and  
• 
percentage of participants maintaining the castrate levels from Week 8 to Week 24. 
The percentage of participants achieving castrate levels of serum testosterone (<50 ng/dL or 
1.735 nmol/L) on Day 29 will be obtained as the number of participants with castrate levels at 
the visit, divided by the total number of participants on Day 29 in the considered population.  
Percentage of participants maintaining the castrate levels of serum testosterone (<50 ng/dL or 
1.735 nmol/L) from Week 8 to Week 24 will be calculated as the number of participants with 
castrate levels at all visits from Week 8 to Week 24, divided by the total number of assessable 
participants. 
To derive the percentage of participants maintaining castration levels of testosterone, missing 
data will be handled as follows: 
(a) 
In participants escaping castration at a certain visit, subsequent missing data is irrelevant. 
(b) 
Participants maintaining castration up to a certain visit with missing data afterwards 
(drop-out due to non-drug-related reasons) will be excluded from the analysis. 
(c) 
Participants maintaining castration up to a certain visit with missing data afterwards 
(drop-out due to drug-related reasons) will be treated as having escaped castration 
(failure). 
(d) 
Missing data between two visits where castration levels are maintained will be handled 
as missing for that particular visit, and the participant will be considered to have 
maintained castration. 
To derive the percentage of participants maintaining castrate levels of testosterone, assessable 
participants are defined as the total number of all participants having values at all visits and all 
participants having missing data according to the criteria a), c) and d) mentioned previously. 
Participants having missing data according to the criteria b) will be excluded from this 
calculation. 
Co-primary endpoints will be tabulated with two-sided 95% (95% CI) using the 
Clopper-Pearson exact method. 
9.4.3 
Analysis of Secondary Endpoints 
9.4.3.1 
Prostate-Specific Antigen 
The secondary efficacy variable is the percent change in PSA from baseline (prior to injection) 
measured at Week 12 and Week 24. Percent change in PSA is defined as the absolute value of 
difference between the PSA values at Week 12 and Week 24 and the baseline value divided by 
the baseline value. 
PSA percent change from pre-treatment Day 1 will be reported at each subsequent visit, using 
descriptive statistics. 
9.4.3.2 
Pharmacokinetic and Pharmacodynamic Data Analysis 
Description of Triptorelin and Testosterone Concentrations  
Individual plasma or serum concentrations of triptorelin and testosterone will be listed and 
summarised by visit and time points using descriptive statistics for continuous variables 
(number of available observations, mean, median, SD, minimum, maximum, geometric mean, 
and geometric coefficient of variation (assuming log normally distributed data). Data will be 

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summarised for the PK/PD subset and overall. Individual and mean triptorelin and testosterone 
concentration time profiles, as well as spaghetti plots, will be generated.  
Non-compartmental Analysis  
The PK analysis of triptorelin plasma concentrations and testosterone serum concentrations of 
the rich sampling PK/PD subset will be performed by the non-compartmental analysis (NCA) 
approach using Phoenix WinNonlin PK program version 8.3 or higher. The following PK 
parameters will be calculated if warranted by the data: 
• 
maximum observed concentration (Cmax) 
• 
time to maximum observed blood concentration (tmax) 
• 
(for triptorelin only) area under the plasma concentration time curve from time 0 to the 
time of the last quantifiable concentration (AUClast) 
• 
(for triptorelin only) area under the plasma concentration time curve from time 0 to the 
visit on day 169 (AUC0-169) 
• 
(For testosterone only): time to castration tcast 
Additional PK parameters may be calculated if appropriate. 
Descriptive statistics of PK and PD parameters will be presented for the rich PK analysis set 
for triptorelin and the rich PD analysis set for testosterone. PK and PD parameters will be 
summarised by, but not limited to, n, mean, SD, median, minimum, maximum, geometric SD, 
geometric mean, and geometric coefficient of variation except for tmax where only n, median, 
minimum and maximum values will be reported. 
The NCA analysis will be described in a separate data analysis plan and reported in a standalone 
report. 
Population Pharmacokinetic Analysis 
Population pharmacokinetics (PopPK) modelling will be performed using concentrations 
obtained from all participants in order to describe the pharmacokinetics of triptorelin 6-month 
formulation in the prostate cancer population (if warranted by the data). In addition, 
quantification of the inter-participant variability on PK will be performed and an attempt to 
identify participant characteristics explaining the variability on PK will be made. Historical PK 
data from other studies may also be used to compare the PK profiles from this study against 
other populations. The PK model developed will be used to derive exposure metrics to perform 
an exploratory analysis with efficacy and safety endpoints (should any safety signal emerge). 
Should a trend be observed, PK/PD modelling will be performed to describe the relationship 
between exposure and efficacy and/or safety endpoints. 
Population PK/PD analysis will be described in a separate data analysis plan and presented in 
a stand-alone report. 
9.4.4 
Analysis of Exploratory Endpoint 
9.4.4.1 
Pharmacokinetic/Pharmacodynamic Relationship 
An exploratory analysis will be performed to assess the relationship between PK and PD 
endpoints. If a trend is shown, an attempt to build a PK/PD model using a population approach 
will be performed. The PopPK and PK/PD analyses will be described in a separate data analysis 
plan and reported in a standalone report.   
9.4.5 
Safety Analyses 
Safety endpoints are indicated in Section 3. 
All safety data will be included in the participant data listings. Analyses and summary tables 
will be based upon the safety set. 

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All AEs will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) version 24.1 (or higher if available) and will be classified by MedDRA preferred 
term and system organ class. Adverse event listings will be presented by participant, system 
organ class and PT. 
The incidence of all TEAEs and SAEs will be tabulated overall. In addition, summary tables 
will be presented by maximum intensity and drug relationship. 
A TEAE is defined as any AE that occurs during the active phase of the study (from study 
intervention injection to 24 weeks after injection) if it was not present prior to receiving study 
intervention, or: 
• 
it was present prior to receiving IMP but the intensity increased during the active phase 
of the study. 
• 
It became serious during the active phase of the study 
• 
It was present prior to receiving the study intervention and the intensity was the same, 
but the causality changed to ‘related to treatment’ during the active phase of the study. 
All TEAEs will be flagged in the AEs listings.  
Haematological and biochemical toxicities will be recorded and graded according to the NCI 
CTCAE criteria, where available. The National Cancer Institute-Common Toxicity Criteria for 
Adverse Events (NCI-CTCAE) Grade 3 and 4 haematology and biochemistry variables by 
participant and by cycle will be listed. 
Actual values and changes from baseline in clinical laboratory tests, physical examinations, 
vital signs and 12-lead ECG will be summarized using descriptive statistics at each visit. For 
laboratory data, abnormal values will be flagged in the data listings and a list of clinically 
significant abnormal values will be presented. Shift tables using the worst on-treatment grade 
will be presented for the number and percentage of participants with NCI-CTCAE grades. 
AEs reported by investigators using the NCI-CTCAE classification (Version 5.0 or higher) will 
be coded using MedDRA Version 24.1 (or higher if available).  
Summary incidence tables will be provided, classified by SOC, PT and associated NCI/CTC 
worst grade. In the event of multiple occurrences of the same AEs being reported by the same 
participant, the maximum intensity (Grade 5 >Grade 4 >Grade 3 >Grade 2 >Grade 1 >missing 
>not applicable) will be chosen. 
9.4.6 
Subgroups Analyses 
No subgroups analysis will be performed. 
9.4.7 
Other Analyses 
Not applicable. 
9.5 
Interim Analyses  
No interim analysis will be performed. 
 

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10 
SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with the following: 
• 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organisations of Medical 
Sciences International Ethical Guidelines 
• 
International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines 
• 
Applicable laws and regulations such as Regulation EU 536/2014 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (e.g. any participant recruitment materials) must be approved by the IRB/IEC 
before the study is initiated. 
• 
Any amendments to the protocol will require IRB/IEC approval before implementation 
of changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. 
• 
The protocol and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate 
hazard to study participants. 
• 
The investigator will be responsible for the following: 
• 
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
• 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• 
Providing oversight of the conduct of the study at the site and adherence to 
applicable 
local 
regulations, 
ICH 
guidelines 
and 
the 
IRB/IEC 
requirements/procedures. 
10.1.2 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and 
for one year after completion of the study. 
10.1.3 
Informed Consent Process 
• 
The ICF and any participant recruitment materials must be in compliance with ICH GCP, 
local regulatory requirements, and legal requirements, including applicable privacy laws. 
They must be approved prior to use as described in Section 10.1.1. 
• 
The investigator or his/her authorised representative will explain to the participant or 
their legally authorised representative the nature and objectives of the study and possible 
risks and benefits associated with the participation. They will answer all questions 
regarding the study. 

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• 
Participants or their legally authorised representative, when applicable must be informed 
that their participation is voluntary.  
• 
The investigator or his/her authorised representative will obtain written informed consent 
from each participant or the legally authorised representative, when applicable, before 
any study-specific procedure is performed. The investigator will retain the original of 
each participant’s signed ICF. 
• 
A copy of the signed ICF(s) must be provided to the participant or their legally authorised 
representative. 
• 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorised person obtaining the informed consent must also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study. If changes to the ICF do not apply to all participants, this will 
be communicated to the IRB/IEC with a rationale. IRB/IEC approval must be received 
before implementation as required by local regulations. 
• 
The ICF will contain a separate section that addresses the use of all data combined with 
data from prostate cancer patients from other parts of the world. These data may only be 
used for analysis to advance science and public health, including in order to: 
• 
understand and evaluate the study drug and/or other drugs,  
• 
better understand the studied disease and associated health problems, 
• 
develop new drugs and find new ways to detect, treat, prevent or cure health 
problems, 
• 
plan new studies or improve scientific analysis methods, 
• 
publish research results in scientific journals or use them for educational purposes, 
• 
conduct additional statistical analysis. 
• 
Participants will be told that they are free to refuse to participate and may withdraw their 
consent at any time and for any reason during the study.  
• 
If a pregnancy is reported for a female partner of a male participant during the study, the 
partner will be asked to sign appropriate consent for the sponsor to follow the outcome 
of the pregnancy. 
10.1.4 
Data Protection 
• 
Participants will be assigned a unique identifier by the sponsor. Any participant records 
or datasets that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred. 
• 
The participant must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the participant who will be required to give consent for their data to 
be used as described in the informed consent.  
• 
The participant must be informed that his/her medical records may be examined by the 
sponsor’s auditors or other authorised personnel appointed by the sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
• 
The sponsor will ensure that appropriate organisational and technical arrangements are 
implemented to comply with the applicable rules on the protection of personal data. In 
the event of a potential data security breach concerning personal data processed on behalf 

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of the sponsor, the data protection officer must be informed without undue delay and no 
later than 24 hours from the discovery of the event. The data protection officer will 
evaluate the event and notify the Data Protection Authorities within 72 hours, if required. 
Corrective actions and preventive actions will be implemented to mitigate the possible 
adverse effects. Affected study participants will be informed accordingly. Ipsen Data 
Protection Officer can be contacted by email: dataprivacy@ipsen.com. 
• 
When permitted by local regulation, the ICF will contain a separate section that addresses 
the remote access by the study monitors to source documents/data for the purpose of 
source data verification. A specific consent will be required to document a participant’s 
agreement. 
10.1.5 
Dissemination of Clinical Study Data 
• 
The sponsor seeks to publish the results of its clinical trials in biomedical journals, 
whatever the outcome. Clinical trial results may also be presented at international 
congresses as posters or oral presentations. 
• 
Protocol and result summary will be made publicly available on the US Clinical Trials 
Registry (ClinicalTrials.gov). The sponsor also provides clinical trial information to 
other 
national 
clinical 
trial 
registries 
or 
databases 
according 
to 
local 
requirements/legislation. 
• 
A clinical study report will be prepared if at least one participant has signed informed 
consent and received intervention, regardless of whether the study is completed or 
prematurely terminated. The clinical study report may be disclosed according to 
regulatory requirements.  
10.1.6 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded in the CRF unless transmitted 
to the sponsor or designee electronically (e.g. laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by signing the CRF. 
• 
All entries in the CRF will be made under the e-signature of the person performing the 
action. This electronic signature consists of an individual and confidential username and 
password combination. It is declared to be the legally binding equivalent of the handwritten 
signature. Only sponsor authorised users will have access to the CRF as appropriate to their 
study responsibilities. Users must have successfully undergone software application 
training prior to entering data into the CRF. 
• 
Guidance on completion of CRFs will be provided in CRF completion guidelines. 
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory authority inspections, and provide direct access to all trial related sites, source 
data/documents, and reports for the purpose of monitoring and auditing, and inspection 
by domestic and foreign regulatory authorities. 
• 
Monitoring details describing strategy, including definition of study critical data items 
and processes (e.g. risk-based initiatives in operations and quality such as Risk 
Management and Mitigation Strategies and Analytical Risk-Based Monitoring), 
methods, responsibilities and requirements, including handling of noncompliance issues 
and monitoring techniques (central, remote, or on-site monitoring) are provided in the 
Monitoring Plan. 
• 
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 

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• 
The sponsor assumes accountability for actions delegated to other individuals (e.g. 
Contract Research Organisations). 
• 
Records and documents, including signed ICFs, pertaining to the conduct of this study 
should be retained by the investigator according to the ICH-GCP guidelines, to local 
regulations, or as specified in the study agreement, whichever is longer. No records may 
be destroyed during the retention period without the written approval of the sponsor. No 
records may be transferred to another location or party without written notification to the 
sponsor. 
10.1.7 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site. 
• 
Data reported in the CRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available. 
• 
Definition of what constitutes source documents/data and their location will be 
documented in a specific form. 
• 
The investigator must maintain accurate documentation that supports the information 
entered in the CRF. Source data must be attributable, legible, contemporaneous, original, 
accurate and complete. 
• 
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorised site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. When 
permitted by local regulation and guidance, study monitors will access remotely to source 
documents/data to conduct source data verification, while maintaining appropriate 
security measures and ensuring the protection of the data. This will be described in the 
monitoring plan or equivalent. 
10.1.8 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants or the actual date on which the first participant is enrolled. 
Study/Site Termination 
There are no formal rules for early termination of this study. 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
For study termination: 
• 
Discontinuation of further study intervention development 

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For site termination: 
• 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate or no recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by 
the applicable regulatory requirements. The investigator shall promptly inform the participant 
and should assure appropriate participant therapy and/or follow-up. 
10.1.9 
Publication Policy 
• 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor 
before submission. This allows the sponsor to protect proprietary information and to 
provide comments. 
• 
The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicentre studies only in their entirety and not as individual site data. In 
this case, a coordinating investigator will be designated by mutual agreement. 
• 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 

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10.2 
Appendix: Clinical Laboratory Tests 
• 
The tests detailed in Table 6 will be performed locally. 
• 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations. 
• 
Refer to SoA Section 1.3 for details of visits. 
Table 6 
Protocol-Required Safety Laboratory Tests 
Parameters 
Screening 
Intervention Period 
EoS/EW 
Haematology 
X 
X 
X 
Platelet Count 
X 
X 
X 
Haemoglobin 
X 
X 
X 
White blood cell count with differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
X 
X 
X 
Clinical Chemistry 
 
 
 
Creatinine 
X 
X 
X 
Glucose (fasted at screening and fasted on Day 1 and 
Day 169) [a] 
X 
X 
X 
Aspartate aminotransferase 
X 
X 
X 
Alanine aminotransferase 
X 
X 
X 
Alkaline phosphatase 
X 
X 
X 
Bilirubin (total and conjugated) 
X 
X 
X 
EoS=end of study; EW=early withdrawal 
a Fasting not necessary for diabetic participants.  
Note: All parameters will be analysed locally. The preparation and storage of samples will be performed per each 
local laboratory practice. 
 
Investigators must document their review of each laboratory safety report. 
 

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• 
Contacts for SAE reporting can be found on the SAE form and the cover sheet. 
 

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10.4 
Appendix: American Joint Committee on Cancer (AJCC) TNM Staging System 
for Prostate Cancer 
The treatment of prostatic carcinoma is predicated largely on the stage of the disease; accurate 
staging is therefore essential. 
The TNM staging system classifies the disease according to the progression of the primary 
tumour, the spread to the regional lymph nodes, and the development of distant metastases 
(hence TNM). Each stage is further subdivided (e.g. T1-T4 and Tla-T4) to give more detailed 
information about progression within each category. 
 
Primary Tumour (T) 
Clinically inapparent tumour neither palpable nor visible by imaging: 
 
Tumour incidental histologic finding in 5% or less of tissue resected 
Tumour incidental histologic finding in more than 5% of tissue resected 
Tumour identified by needle biopsy (e.g. because of elevated PSA) 
Tumour confined within prostate 
Tumour found in one or both lobes by needle biopsy, but not palpable, or reliably visible 
by imaging is classified as TIc 
Tumour involves one half on one lobe or less 
Tumour involves more than one half of one lobe but not both lobes 
Tumour involves both lobes 
Tumour extends through the prostate capsule 
Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is classified not as T3 
but T2. 
Extracapsular extension (unilateral or bilateral) 
Tumour invades seminal vesicles 
Tumour is fixed or invades adjacent structures other than seminal 
vesicles: bladder neck, external sphincter, rectum, levator muscles 
and/or pelvic wall 
T 
T1 
 
Tla 
Tl b 
Tl c 
T2 
 
 
T2a 
T2 b 
T2 c 
T3 
 
 
T3a 
T3b 
T4 
 
Regional Lymph Nodes (N) 
No regional lymph node metastasis 
Metastasis in regional lymph node(s) 
N 
NO 
N1 
Distant metastasis (M) 
No distant metastasis 
Distant metastasis 
Non-regional lymph node(s) 
Bone(s) 
Other site(s) with or without bone disease 
M 
MO 
M1 
Mla 
Mlh 
Mlc 

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10.5 
Appendix: ECOG Performance Scale 

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2.3.1 / Risk 
Assessment 
 
A risk assessment for this study is provided in Table 3. 
Table 3 Study Risk Assessment 
Potential Risk of 
Clinical Significance 
Summary of 
Data/Rationale 
for Risk 
Mitigation 
Strategy 
Study Intervention: Triptorelin 
There is no major 
known nonclinical risk 
associated with the 
study intervention 
Clinical risks associated 
with 
the 
study 
intervention 
may 
include:  
• 
hot flushes 
• 
erectile 
dysfunction 
• 
loss of libido 
• 
impaired physical 
activities 
• 
metabolic 
syndrome 
• 
cardiovascular 
events 
• 
anxiety/depression 
• 
decreased bone 
mineral density 
• 
risk of abortion or 
foetal abnormality 
[b] 
See Section 8.3 
See IB Section 
6.6.1 
Participant 
selection: 
Participants 
with 
significant 
medical 
conditions 
and at high 
risk of 
presenting 
treatment 
related SAEs 
and 
high-grade 
toxicity will 
be excluded 
from the 
study. 
Participant 
monitoring: 
During the 
study, there 
will be close 
monitoring 
of the 
participants 
for safety 
including 
local 
tolerability 
Addition per new 
template 

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11 
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Botto H et al.: Decapeptyl in the treatment of metastatic prostatic cancer. Comparative study 
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Breul J, Lundstrom EA, Purcea D et al. Efficacy of testosterone suppression with 
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De Sy WA, De Wilde P, De Meyer JM et al.: Long term experience in the treatment of advanced 
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Lundstrom EA, Rencken RK, van Wyk JH et al. Triptorelin 6-month formulation in the 
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National Health Commission China. Chinese guidelines for diagnosis and treatment of prostate 
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P P D
P P D
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