Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3556050 for the Treatment of Osteoarthritis Pain
Phase: PHASE2
Conditions: Osteoarthritis
Sponsor: Eli Lilly and Company

This study H0P-MC-OA03 (NCT04627038) is a sub-study of Master Protocol H0P-MC-CPMP 
(NCT05986292) 
 
Protocol: H0P-MC-OA03(a)  
 
Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3556050 for the Treatment of 
OsteoarthriƟs Pain  
 
NCT04627038  
 
Approval Date: 03-Mar-2021 

C O N FI D E N TI A L  
Pr ot oc ol n u m ber H 0 P -M C -O A 0 3 (a) 
 
1 
Title P a ge  
C o nfi d e nti al I nf or m ati o n  
T h e i nf or m ati o n c o nt ai n e d i n t hi s d o c u m e nt i s c o nfi d e nti al a n d i s i nt e n d e d f or t h e u s e of cli ni c al i n v e sti g at or s. It i s t h e pr o p ert y of 
Eli Lill y a n d C o m p a n y or it s s u b si di ari e s a n d s h o ul d n ot b e c o pi e d b y or di stri b ut e d t o p er s o n s n ot i n v ol v e d i n t h e cli n i c al 
i n v e sti g ati o n of L Y 3 5 5 6 0 5 0 u nl e s s s u c h p er s o n s ar e b o u n d b y a c o nfi d e nti alit y a gr e e m e nt wit h Eli Lill y a n d C o m p a n y or it s 
s u b si di ari e s.  
 
N ot e t o R e g ul at or y A ut h oriti e s:   T hi s d o c u m e nt m a y c o nt ai n pr ot e ct e d p er s o n al d at a a n d/ or c o m m er ci all y c o nfi d e nti al 
i nf or m ati o n e x e m pt fr o m p u bli c di s cl o s ur e. Eli Lill y a n d C o m p a n y r e q u e st s c o n s ult ati o n r e g ar di n g r el e a s e/r e d a cti o n pri or t o an y 
p u bli c r el e a s e. I n t h e U nit e d St at e s, t hi s d o c u m e nt i s s u bj e ct t o Fr e e d o m of I nf or m ati o n A ct ( F OI A) E x e m pti o n 4 a n d m a y n ot b e 
r e pr o d u c e d or ot h er wi s e di s s e mi n at e d wit h o ut t h e writt e n a p pr o v al of Eli Lill y a n d C o m p a n y or it s s u b si di ari e s. 
 
M aster Pr ot oc ol Title:  A Master Pr ot oc ol f or Ra n d o mize d, Place b o - C o ntr olle d, P hase 2 
Cli nical Trials of M ulti ple I nter ve nti o ns f or t he Treat m e nt of C hr o nic Pai n  
M aster Pr ot oc ol N u m ber: H 0 P -M C -C P M P  
I S A Title: Ra n d o mize d, Place b o - C o ntr olle d, P hase 2 Cli nical Trial t o E val uate L Y 3 5 5 6 0 5 0 f or 
t he Treat me nt of Oste oart hritis Pai n 
I S A N u m ber: H 0 P -M C -O A 0 3  
A me n d me nt N u m ber: a 
C o m p o u n d : L Y 3 5 5 6 0 5 0 
St u d y P h ase: 2 
S h ort Title:  Cli nical Trial t o E val uate L Y 3 5 5 6 0 5 0 f or t he Treat me nt of Oste oart hritis Pai n  
Acr o n y m : O A 0 3 
S p o ns or N a me: Eli Lill y a n d C o m pa n y  
Le g al Re gistere d A d dress: I n dia na p olis, I n dia na, U S A 4 6 2 8 5 
Re g ul at or y A ge nc y I de ntifier N u m ber :   
Master Pr ot oc ol I N D 1 4 4 9 1 5 
L Y 3 5 5 6 0 5 0 I N D 1 2 9 7 5 6 
A p pr o v al D ate: Pr ot oc ol  a me n d me nt (a) Electr o nicall y  Si g ne d a n d A p pr o ve d b y Lill y o n date 
pr o vi de d bel o w.  
 
 
A p pr o v al D at e: 0 3- M ar- 2 0 2 1 G M T

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Protocol number H0P-MC-OA03(a)
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Medical Monitor Name and Contact Information will be provided separately.

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Protocol number H0P-MC-OA03(a) 
 
3 
Protocol Amendment Summary of Changes Table 
 
DOCUMENT HISTORY 
Document 
Date 
Original Protocol 
25 August 2020 
Amendment [a]  
Overall Rationale for the Amendment: 
This amendment addresses a new dose titration scheme for participants. 
 
 and decisions to change the dose level will be made by the investigator, in discussion 
with the participants, based on adverse events reported for tolerability. The changes for dose 
titration affect sections throughout the ISA. Additional updates were made according to 
emerging data and changes to the master protocol. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
Updates made to 
 
Number of Participants 
 
Intervention Groups and 
Duration, and 
 
Data Monitoring Committee 
Sample size and study intervention text updated for 
new dose titration scheme 
“Data monitoring committee” changed to 
“Assessment committee” for consistency with 
master CPMP protocol 
1.2 Schema 
Updated schema to show dose 
titration  
New dose titration scheme for participants 
1.3 Schedule of 
Activities (SoA) 
Added telephone visits and 
updated study intervention notes 
to include a link to the new dose 
modification section 
To implement new dose titration scheme 
1.3 Schedule of 
Activities (SoA) 
Updates were made to ECG and 
Vital signs 
Corrections for clarity 
1.3 Schedule of 
Activities (SoA) 
Replaced urinalysis with urine 
drug screen. 
Urinalysis was only for Visit 3, so removed. Urine 
drug screen added and performed according to 
investigator discretion 
1.3 Schedule of 
Activities (SoA) 
Added window for PK sample 
collection 
Adding flexibility 
1.3 Schedule of 
Activities (SoA) 
Added participant digital 
biomarker device for Visit 7 and 
ED 
To indicate when the participant needs to return the 
device. 
2.2 Background 
Updated information for the 2 
Phase 1 clinical studies 
Both studies are completed 
4.1 Overall Design 
Updated and added text to 
describe the new dose titration 
scheme 
New dose titration scheme for participants 
4.3 Justification for 
Dose 
Added text for the titration 
scheme 
Removed “preliminary” from the 
beginning of second paragraph 
New dose titration scheme for participants 
 
Study LXBA is now completed 
5.2 Exclusion Criteria 
Updated Criteria #1028 and 
Clarifications based on clinical experience and 
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Protocol number H0P-MC-OA03(a) 
 
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Section # and Name 
Description of Change 
Brief Rationale 
#1034 
emerging pharmacokinetic/metabolism data 
5.3 Lifestyle 
Considerations 
Removed text that is already in 
the master CPMP 
Master protocol updates for CPMP amendment (a) 
6.1 Study 
Intervention(s) 
Administered 
Updated text and table 
New dose titration scheme for participants. 
Emerging data allow participants to take capsules 
with or without food 
Changed “pharmacy instructions” to “pharmacy 
manual” 
6.5 Concomitant 
Therapy 
Removed text that is duplicated 
in CPMP 
Added text for drug-drug 
interactions 
Consistency across ISAs 
6.6 Dose Modification 
New section 
New dose titration scheme for participants  
8.2 Adverse Events and 
Serious Adverse Events 
Added text to refer to the master 
Master protocol contains AE and SAE information 
9.2 Sample Size 
Determination 
Updated sample size 
New dose titration scheme for participants 
9.3 Populations for 
Analyses 
Removed “in the SAP” 
The master protocol defines the populations for 
analyses 
10.2 Appendix 2  
Updated text 
Updates to internal Lilly guidance 
Throughout the 
protocol 
Minor editorial and formatting 
changes 
Minor, therefore not described 
 
 
 

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Protocol number H0P-MC-OA03(a)
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Table of Contents
1.
Protocol Summary......................................................................................................7
Synopsis.......................................................................................................................7
Schema.........................................................................................................................8
Schedule of Activities (SoA) ........................................................................................9
2.
Introduction..............................................................................................................13
Study Rationale ..........................................................................................................13
Background ................................................................................................................13
Benefit/Risk Assessment ............................................................................................14
2.3.1.
Risk Assessment.........................................................................................................14
2.3.2.
Benefit Assessment.....................................................................................................14
2.3.3.
Overall Benefit:  Risk Conclusion...............................................................................15
3.
Objectives and Endpoints.........................................................................................16
4.
Study Design .............................................................................................................17
Overall Design............................................................................................................17
Scientific Rationale for Study Design .........................................................................18
Justification for Dose..................................................................................................18
End of Study Definition..............................................................................................18
5.
Study Population ......................................................................................................19
Inclusion Criteria........................................................................................................19
Exclusion Criteria.......................................................................................................19
Lifestyle Considerations .............................................................................................20
6.
Study Intervention....................................................................................................21
Study Intervention(s) Administered ............................................................................21
Preparation/Handling/Storage/Accountability .............................................................21
Measures to Minimize Bias:  Randomization and Blinding .........................................22
Study Intervention Compliance...................................................................................22
Concomitant Therapy .................................................................................................22
Dose Modification......................................................................................................22
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................24
Discontinuation of Study Intervention ........................................................................24
8.
Study Assessments and Procedures .........................................................................25
Safety Assessments ....................................................................................................25
8.1.1.
Vital Signs..................................................................................................................25
8.1.2.
Electrocardiograms.....................................................................................................25
8.1.3.
Clinical Safety Laboratory Assessments .....................................................................25
Adverse Events and Serious Adverse Events ..............................................................25
Treatment of Overdose ...............................................................................................25
Pharmacokinetics........................................................................................................25
Pharmacodynamics.....................................................................................................26
.................................................................................................................26
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9.
Statistical Considerations.........................................................................................27
Statistical Hypotheses.................................................................................................27
Sample Size Determination.........................................................................................27
Populations for Analyses ............................................................................................27
Statistical Analyses.....................................................................................................27
9.4.1.
General Considerations...............................................................................................28
9.4.2.
Pharmacokinetics and Pharmacodynamics ..................................................................28
9.4.3.
Tertiary/Exploratory ...................................................................................................28
9.4.4.
Biomarkers .................................................................................................................28
Interim Analyses.........................................................................................................28
10.
Supporting Documentation and Operational Considerations ................................29
Appendix 1:  Clinical Laboratory Tests.......................................................................29
Appendix 2:  Definitions of Reproductive Requirements and 
Contraceptive Guidance..............................................................................................30
Appendix 3:  Provisions for Changes in Study Conduct During 
Exceptional Circumstances.........................................................................................34
Appendix 4:  Abbreviations ........................................................................................37

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Protocol number H0P-MC-OA03(a)
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1.
Protocol Summary
Synopsis
Protocol Title: Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate 
LY3556050 for the Treatment of Osteoarthritis Pain
Rationale:
The purpose of this study is to test whether LY3556050 is efficacious in relieving osteoarthritis 
(OA) pain in the knee. Data will be collected to assess the safety and tolerability of LY3556050
in this study population. Pharmacokinetic properties and pharmacodynamic effects will also be 
explored. The totality of data from this proof-of-concept study will assess the benefits and risks
associated with LY3556050 and inform decisions for the clinical development of LY3556050.
Objectives and Endpoints:
The primary and secondary objectives and endpoints are stated in the master protocol 
H0P-MC-CPMP (CPMP) and OA disease-state addendum (DSA; CPMP[1]).
Overall Design:
This is an 8-week, Phase 2, randomized, double-blind, placebo-controlled study that will 
compare LY3556050 versus placebo in participants with OA in the knee.
Disclosure Statement: This is a randomized, investigator- and participant-blind, 
placebo-controlled, Phase 2 clinical trial.
Number of Participants:
Up to 200 participants will be randomized in a 
 ratio to LY3556050 and placebo, respectively,
with the assumption that approximately 33% of the participants will drop out prior to the end of 
the double-blind treatment period. 
Intervention Groups and Duration:
Participants will receive either LY3556050 or placebo. Based on tolerability, participants may
take up to a maximum of 3 capsules orally (each capsule is 
), twice daily, approximately 
every 12 hours, for a total dose of 600 mg.  
This is an 8-week study.
Data Monitoring Committee: Yes.  
Safety reviews are covered by the Assessment Committee charter for the Chronic Pain Master 
Protocol.
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Protocol number H0P-MC-OA03(a)
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Schedule of Activities (SoA)
This SoA shows visits and procedures unique to the intervention-specific appendix (ISA) H0P-MC-OA03 (OA03) for LY3556050. 
Please refer to master protocol CPMP and the OA DSA CPMP(1) SoAs for additional information.  

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Protocol number H0P-MC-OA03(a)
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H0P-MC-OA03
ISA
Randomization
Double-Blind Treatment
Early
Discontinu
ation
Notes
Visit Number
V3
V4
V5
V6
V7
ED
Study Week
0
2
4
6
8
Visit Window (days)
±3
±3
±3
±3
Telephone visit
Xa,b
Visit window +2 days
There will be 2 telephone visits between Visit 3 and Visit 4:
a Visit occurs 4 days after Visit 3
 
b Visit occurs 8 days after Visit 3 
 
  
Procedures
Evaluate all I/E criteria
X
Physical examination
X
X
X
X
X
X
V3-V7:  Do symptom-directed physical examination
ECG
X
X
X
X
X
X
V3, V5 and V7:  Single ECG before in-clinic dosing and at 3 hours after 
dosing
V4, V6 and ED:  Single ECG
ECG includes collection of PR interval, QRS duration and interval, and heart 
rate.
Vital signs
X
X
X
X
X
X
Blood Pressure
V3, V5, and V7: Collect blood pressure and pulse in supine and standing 
position, before in-clinic dosing and at 3 hours after dosing
V4, V6 and ED:  Collect blood pressure once
Collect orthostatic blood pressure after 5 minutes supine and then 2-3 minutes 
after standing and collect pulse after supine and standing blood pressure.
Temperature and Respiratory rate
Collect once at each visit
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H0P-MC-OA03
ISA
Randomization
Double-Blind Treatment
Early
Discontinu
ation
Notes
Visit Number
V3
V4
V5
V6
V7
ED
Study Week
0
2
4
6
8
Visit Window (days)
±3
±3
±3
±3
Telephone visit
Xa,b
Study intervention
X
X
X
X
X
Intervention is taken orally, twice daily (BID), approximately every 12 hours.
V3, V5, and V7:  Participants take the morning dose in the clinic.
Refer to Section 6.6 for dose titration scheme.
Intervention compliance
X
X
X
X
X
Laboratory Tests and Sample Collection
Hematology
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
Urine drug screen
Performed at investigator discretion
Serum pregnancy
X
X
X
X
X
For WOCBP only
Urine pregnancy
X
For WOCBP only
Collect sample within 24 hours prior to first dose.
Lipid panel
X
X
X
X
X
X
Thyroid panel
X
X
X
X
X
X
Cystatin C
X
X
X
X
X
X
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Protocol number H0P-MC-OA03(a)
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H0P-MC-OA03
ISA
Randomization
Double-Blind Treatment
Early
Discontinu
ation
Notes
Visit Number
V3
V4
V5
V6
V7
ED
Study Week
0
2
4
6
8
Visit Window (days)
±3
±3
±3
±3
Telephone visit
Xa,b
Visit window +2 days
There will be 2 telephone visits between Visit 3 and Visit 4:
a Visit occurs 4 days after Visit 3
 
b Visit occurs 8 days after Visit 3
 
  
HbA1c
X
X
PK sample
X
X
X
X
X
X
V3:  Collect 3 hours ±15 minutes after dosing.
V5 and V7:  Collect samples before dosing and 3 hours ±15 minutes after 
dosing.
V4, V6, and ED:  Collect single sample at any time.
Record date and time of collection.
Somatostatin-related
biomarker sample
X
X
X
X
X
X
Participant Device
Participant returns device
X
X
Abbreviations:  ECG = electrocardiogram; ED = early discontinuation; HbA1c = glycated hemoglobin; I/E = inclusion and exclusion; ISA = intervention-specific 
appendix; PK = pharmacokinetic; V = visit; WOCBP = women of childbearing potential.
CCI
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Protocol number H0P-MC-OA03(a) 
 
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2. 
Introduction 
This ISA, H0P-MC-OA03 (OA03), is an appendix to the master protocol CPMP and contains 
unique study elements specific for LY3556050. The master protocol contains the overarching 
study elements that govern the OA DSA CPMP(1) and this ISA OA03.   
 
Study Rationale 
The purpose of this study is to test whether LY3556050 is efficacious in relieving OA pain in the 
knee. Data will be collected to assess the safety and tolerability of LY3556050 in this study 
population. Pharmacokinetic (PK) properties and pharmacodynamic (PD) effects will also be 
explored. The totality of data from this proof-of-concept study will assess the benefits and risks 
associated with LY3556050 and inform decisions for the clinical development of LY3556050.  
 
Background 
Somatostatin (SST) is an inhibitory neuropeptide exerting its activity via 5 different SST 
receptor (SSTR) subtypes, named SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5. Most are 
involved in homeostatic regulation of polypeptide hormones. Given its neuronal distribution, 
SSTR4 has been of interest for its ability to modulate sensory nerve transmission and pain 
response.   
LY3556050 is a selective, potent, and full agonist of the human SSTR4 and is under 
development as an oral analgesic for chronic pain. A detailed description of the chemistry, 
pharmacology, PK, and safety of LY3556050 is provided in the Investigator’s Brochure (IB).   
Two Phase 1 clinical studies in healthy participants are completed, CNTX-0290-101 (CNTX) 
and J2P-MC-LXBA (LXBA). The CNTX and LXBA study results are available in the IB.   
Pharmacokinetics 
The PK data from Study LXBA Part A were consistent with those observed in Study CNTX and 
support twice-daily dosing. 
Safety 
The highest dose of 600 mg every 12 hours is considered safe and well-tolerated in healthy 
participants. 
 
 

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Protocol number H0P-MC-OA03(a)
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Benefit/Risk Assessment
The IB provides detailed information about the known and expected benefits and risks and 
reasonably expected adverse events (AEs) of LY3556050.  
2.3.1.
Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for 
Risk
Mitigation Strategy
Study Intervention LY3556050
Cardiovascular
HR: Variable data across clinical 
studies and across doses
PR interval: Concentration-related 
increase in duration with large 
variability
QRS interval: Concentration-related 
increase in duration
Vital signs and ECGs evaluated at 
each visit. Cardiovascular safety 
parameters to be evaluated include:
HR, PR and QRS intervals, and 
orthostatic vital signs.
Additional participant exclusion 
criteria to protect those with a 
potential risk.
Discontinuation criteria for clinically 
significant changes.
Thyroid
TSH increases observed in 
Study LXBA
Labs evaluated at each visit to
monitor thyroid function.
Additional participant exclusion 
criteria to protect those with a 
potential risk.
Discontinuation criteria for clinically 
significant changes.
Abbreviations:  ECG = electrocardiogram; HR = heart rate; TSH = thyroid-stimulating hormone.
2.3.2.
Benefit Assessment
This is the first study evaluating efficacy of LY3556050 in participants with OA.
Potential benefits for the study participants include 

study-related medical procedures 
o
physical examinations, 
o
laboratory tests 
o
electrocardiograms (ECGs) 

detailed evaluations of OA 
o
knee examinations 
o
knee x-rays, and

OA-associated questionnaires that may improve participants understanding of their own 
condition. 
As part of the master protocol CPMP, participants to this ISA will report their experiences using 
standard tools that will contribute to the assessment of novel treatments for OA.  In addition, data 
collected from this study may also improve our understanding of chronic pain. Together, these

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Protocol number H0P-MC-OA03(a)
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may lead to the development of a new treatment with an improved safety and efficacy profile 
compared to standard of care.
2.3.3.
Overall Benefit:  Risk Conclusion
The measures taken to minimize risk to participants in this study and the potential risks identified 
in association with ISA OA03 are justified by the anticipated benefits to participants with OA.

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3.
Objectives and Endpoints
The master protocol CPMP and OA DSA CPMP(1) include objectives and endpoints applicable 
for this study. This table describes objectives and endpoints specific for LY3556050.
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Protocol number H0P-MC-OA03(a)
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4.
Study Design
Overall Design
Master protocol CPMP describes the overall study design and study design rationale. This 
section describes visits and overall procedures unique to ISA OA03 for LY3556050 in addition 
to the procedures outlined in master protocol CPMP and DSA CPMP(1).  
Double-Blind Treatment Period (Visits 3 through 7)
If the participant receives at least 1 dose of intervention and discontinues during the double-blind 
treatment period, they should complete early discontinuation procedures per the master 
protocol CPMP, OA DSA CPMP(1), and the OA03 Schedule of Activities (SoA). If there are 
duplicate procedures, follow the OA03 SoA.
Visit 3
At Visit 3 post randomization

the site completes the OA03 baseline procedures and sample collection 

participants receive their first dose of study intervention and instructions for dosing at 
home

the site completes all post treatment sample collection and safety monitoring, and

the site instructs participants to continue with study restrictions and Numeric Rating 
Scale (NRS) diary entries before their visit discharge.
Telephone Visits
Visit 3 +4 days
Four days after Visit 3, with a window of +2 days, participants will complete a telephone visit 
with the site.  
The site will review available safety data and study intervention compliance.  
The investigator in discussion with participant will determine if the dose will be increased or if
the participant will be discontinued.  
Visit 3 + 8 days
Eight days after Visit 3, with a window of +2 days, participants will complete a telephone visit 
with the site.  
The site will review available safety data and study intervention compliance. 
The investigator in discussion with participant will determine if the dose will be increased or if 
the participant will be discontinued.
Dose modification guidance is provided in Section 6.6.

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Protocol number H0P-MC-OA03(a) 
 
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Visit 4  
Visits 4 through 7 
At Visits 4 through 7, the site 
 reviews available safety data and completes predose procedures and sample collection 
 reviews diary compliance  
 reviews study intervention compliance 
 completes all posttreatment sample collection and safety monitoring, and 
 instructs participants to continue with study restrictions and NRS diary entries before 
their visit discharge.  
 
 
Scientific Rationale for Study Design 
The master protocol describes the overall study design rationale. 
Section 2.3 describes elements included in this study to further monitor cardiovascular and 
thyroid function, and the associated rationale.   
 
Justification for Dose 
The dose level of 600 mg twice daily (BID) was determined by current clinical data, efficacy 
pharmacology, and nonclinical safety data detailed in the IB. A titration scheme is included to 
maximize tolerability of this target dose.   
Safety data from Study LXBA, and the clinical monitoring plan for this ISA, support testing the 
proposed dose regimen in participants with chronic pain conditions. 
The observed LY3556050 exposure following repeated administration of 600 mg BID exceeds 
the exposure in rats where maximal pharmacological activity was consistently demonstrated 
across rodent models of neuropathic pain. However, it is not known what exposure is required 
for efficacy in the target patient population. Therefore, the highest dose (600 mg BID) previously 
evaluated in Study LXBA was selected for this study as this dosing regimen was observed to be 
well-tolerated in healthy subjects and supported by an adequate margin of safety, based on both 
monkey and rat repeated-dose toxicity studies (IB).  
 
End of Study Definition 
A participant is considered to have completed this ISA if he or she has completed all required 
phases of the study including the last scheduled procedure shown in the ISA SoA. 
The end of the study is defined as the date of the last visit of the last participant in the study or 
last scheduled procedure shown in the ISA SoA for the last participant.  
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Protocol number H0P-MC-OA03(a)
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5.
Study Population
The master protocol CPMP and OA DSA CPMP(1) provide eligibility criteria that must be
followed for this study. LY3556050 specific inclusion and exclusion criteria are listed here.
Inclusion Criteria
Participants are eligible to be included in the study only if all the following criteria apply:
[1025]
are men or women who abide by the reproductive and contraceptive requirements 
provided in OA03 Section 10.2, Appendix 2.
Women of childbearing potential (WOCBP) may participate and include those 
who

are completely abstinent or in a same-sex relationship, as part of their 
preferred and usual lifestyle, must agree to either remain abstinent or stay in 
a same-sex relationship without sexual relationships with males, or 

must agree to use 1 highly effective method of contraception (less than 
1% failure rate), or a combination of 2 effective methods of contraception, 
for the entirety of the study.  
Women not of childbearing potential may participate and include those who 

have a congenital anomaly such as Müllerian agenesis 

are infertile due to surgical sterilization, or 

are postmenopausal.  
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
[1026]
have a history within 2 years prior to Visit 1or current evidence of syncope, 
presyncope, uncontrolled vertigo, or postural dizziness, judged to be clinically 
significant by the investigator
[1027]
have a QRS interval ≥120 msec at Visit 1 or Visit 2
[1028]
have a non-evaluable PR interval or a PR interval >200 msec at Visit 1 or Visit 2
[1029]
have a heart rate <40 bpm at Visit 1 or Visit 2
[1030]
have an estimated glomerular filtration rate (eGFR) of less than 
60 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) formula at Visit 1 or Visit 2
[1031]
have clinically significant active thyroid disease, including Hashimoto’s 
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Protocol number H0P-MC-OA03(a)
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Prior/Concomitant Therapy
[1032]
have been on thyroid replacement therapy or supplements for less than 12 weeks
or had a change in thyroid replacement therapy or supplements in the last 
12 weeks before Visit 2
[1033]
have had a change in beta blocker therapy in the last 12 weeks before Visit 2. This 
does not include a discontinuation of therapy.
[1034]
are taking medications that are known MATE1 or OCT2 substrates with the risk 
for potentially clinically significant drug-drug interactions, such as metformin, 
dofetilide and dalfampridine
Other Exclusions
[1035]
are pregnant or breastfeeding.
Lifestyle Considerations
Reproductive and Contraception Requirements
Reproductive requirements and contraceptive guidance are provided in OA03 Section 10.2, 
Appendix 2. Participants should maintain a consistent lifestyle throughout participation as much 
as possible. Refer to master protocol CPMP Section 5.3 for additional details.  

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6.
Study Intervention
Study Intervention(s) Administered
Participants will take capsules orally BID, approximately every 12 hours, with or without food.  
Intervention Name
LY3556050
Placebo
Dose Formulation
capsule
capsule
Unit Dose 
Strength(s)
/capsule
Not applicable
Dosage Level(s)
 mg BID, approximately 
every 12 hours
Placebo match BID
Route of 
Administration
oral
oral
Use
experimental 
placebo
IMP and NIMP
IMP 
IMP and NIMP
Sourcing
LY3556050 from Lilly
Placebo will be packaged, labeled, distributed, and 
dispensed as IMP by Lilly
Packaging and 
Labeling
In bottles
In bottles
Abbreviations:  BID = twice daily; IMP = investigational medicinal product; NIMP = non-investigational medicinal 
product.
Preparation/Handling/Storage/Accountability
The investigator or designee must confirm appropriate storage 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 enrolled in the study may receive study intervention and only authorized 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 labeled storage conditions with access limited to the investigator and authorized site 
staff.
The investigator or designee is responsible for study intervention accountability, reconciliation, 
and record maintenance, that is, receipt, reconciliation, and final disposition records.
The pharmacy manual contains further guidance and information for the final disposition of 
unused study interventions.
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Measures to Minimize Bias: Randomization and Blinding
This ISA contains no additional stratification factors.
Study Intervention Compliance
A record of the number of LY3556050 or matching placebo capsules dispensed to and taken by 
each participant must be maintained and reconciled with study intervention and compliance 
records.  Intervention start and stop dates, including dates for intervention delays will also be 
recorded in the case report form (CRF).
Concomitant Therapy
The master protocol CPMP provides details on concomitant therapy. Concomitant therapy use 
should remain consistent throughout the study unless changes are medically warranted. Please 
consult the medical monitor for questions.  
Potential Drug-Drug Interactions with LY3556050
Please refer to Section 5.2 for exclusion criteria, the IB and Manual of Operations for details on 
concomitant medication restrictions.
Dose Modification
This protocol allows changes to the dose for individual participants, but the maximum daily dose 
will not exceed 600 mg BID.
.  
Decisions to change the dose level will be made by the investigator in discussion with the 
participants based on the adverse events reported for tolerability. The medical monitor should be 
contacted as needed.  
 
 
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7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
Master protocol CPMP provides the reasons and procedures for discontinuation of intervention 
and participant discontinuation that must be followed for this study. LY3556050-specific 
information is included here. 
Discontinuation of Study Intervention
Cardiovascular Safety
A participant may be permanently discontinued from study intervention for clinically significant 
or symptomatic cardiovascular findings including

QTcF >500 msec

PR interval prolongation >240 msec with symptoms

symptomatic sustained tachycardia (>120 bpm) or bradycardia (<45 bpm) at rest

development of a new left bundle branch block, and 

Mobitz type II second- or third-degree atrioventricular block.
Thyroid Safety
If thyroid-stimulating hormone (TSH) ≥10 at 2 consecutive visits, then a participant will be 
permanently discontinued from study intervention.
If participants have TSH ≥10 at 2 consecutive visits, then 

collect thyroid kit samples

conduct a thyroid ultrasound approximately 2 weeks after the second laboratory time
point, and 

continue testing until issue resolution.

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8.
Study Assessments and Procedures
Study procedures and their timing are summarized in the master protocol CPMP, OA DSA 
CPMP(1), and ISA OA03 SoAs. 
LY3556050-specific assessments and procedures are described here. 
Safety Assessments
The SoA contains the planned time points for all safety assessments.
8.1.1.
Vital Signs
Conduct vital signs measurements for each participant according to the SoA (Section 1.3). 
Follow the study-specific recommendations included in the Manual of Operations.  
8.1.2.
Electrocardiograms
Single 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF
intervals. 
8.1.3.
Clinical Safety Laboratory Assessments
See OA03 Section 10.1 (Appendix 1) for the list of clinical laboratory tests to be performed and 
to the SoA for the timing and frequency for ISA OA03.
Adverse Events and Serious Adverse Events
The master protocol CPMP(a) provides details on adverse event (AE) and serious adverse event 
(SAE) collection, evaluation and follow-up, and SAE reporting.
Treatment of Overdose
There is no known antidote for LY3556050 overdose.
In case of suspected overdose, participants should be monitored for any signs or symptoms of 
adverse reactions or effects, and supportive care should be provided as necessary. 
Pharmacokinetics
Collect venous blood samples of approximately 2 mL as specified in the SoA.  
A maximum of 3 samples may be collected at additional time points during the study if 
warranted and agreed upon between the investigator and the sponsor.
Lilly will provide instructions for the collection and handling of biological samples. 
Site personnel will record

the date and time (24-hour clock time) of LY3556050 administration in the morning
during both in-clinic and at home dosing, and

the date and time (24-hour clock time) of each PK sample.

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Pharmacokinetic samples will be retained for a maximum of 2 years following last subject visit 
for the study. 
 
 
Pharmacodynamics
Pharmacodynamic biomarkers have not been identified to date. Data from this study will be used 
to further evaluate the PD of LY3556050.
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9.
Statistical Considerations
The master protocol and OA DSA provide statistical considerations. LY3556050-specific 
considerations are described here.
Statistical Hypotheses
The master protocol CPMP describes the primary hypothesis. 
 
 
The DSA CPMP(1) describes the secondary hypothesis. The key secondary null hypothesis is 
that there is no difference between LY3556050 and placebo on the key secondary endpoint, the 
mean change from baseline to endpoint for the WOMAC® Pain Subscale Score.
 
Sample Size Determination
Up to 200 participants will be randomized in a 
 ratio to LY3556050 and placebo, respectively.
Assuming an overall dropout rate of approximately 33%,
 
 
. 
 
 
If there is no treatment difference between placebo and LY3556050, the probability of passing 
the efficacy criterion specified above (i.e., false positive) is less than 0.1. The simulation for the 
power calculation and sample size determination was carried out using the Fixed and Adaptive 
Clinical Trial Simulator (FACTS) Version 6.0.
Populations for Analyses
The master protocol CPMP defines the populations for analyses.
The PK population includes all randomized participants who received a dose of LY3556050 and 
have at least 1 evaluable PK sample. 
Statistical Analyses
Any change to the data analysis methods described in this ISA will require an amendment only if 
it changes a principal feature of the ISA. Any other change to the data analysis methods 
described, and the justification for making the change, will be described in the statistical analysis 
plan (SAP) and the clinical study report. Additional exploratory analyses of the data will be 
conducted as deemed appropriate.
The ISA SAP will be finalized prior to unblinding, and it will include a more technical and 
detailed description of the statistical analyses described in this section. 
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9.4.1.
General Considerations
The master protocol CPMP describes the primary endpoint and analyses. 
The master protocol CPMP and DSA CPMP(1) describe the secondary and tertiary/exploratory 
endpoints and analyses.
Any borrowing of placebo or treatment effect information will be specified in the ISA SAP. 
9.4.2.
Pharmacokinetics and Pharmacodynamics
The observed plasma concentrations for LY3556050 will be reported graphically and 
descriptively. 
Model-based PK and PKPD analyses may be conducted to characterize the PK of LY3556050 in 
participants with OA and to explore exposure-response relationships for various PD measures 
using suitable population analysis software. Participant factors may be investigated to assess 
their effects on model parameters. Additional analyses may be conducted, as needed. 
Data from this study may be pooled with data from other studies, if appropriate. Additional 
details on PK and PKPD analyses will be provided in a separate PKPD analysis plan.  
A limited number of prespecified individuals who are not part of the blinded study team and do 
not have direct site contact, data entry, or data validation responsibilities, may receive access to 
unblinded data, prior to the interim or final database lock, in order to initiate the final population 
PKPD model development processes. This will be described in the unblinding plan. Information 
that may unblind the study during the analyses will not be reported to study sites or blinded study 
team until the study has been unblinded.
9.4.3.
Tertiary/Exploratory
All safety analyses will be made on the safety population. Descriptive statistics 
 
 will be conducted as deemed 
appropriate. Confounding factors, such as beta blocker therapy, may be adjusted in the statistical 
models for safety analyses. Subgroup analyses of cardiovascular safety endpoints with beta 
blocker therapy may be conducted accordingly.
9.4.4.
Biomarkers 
Consistent with the master protocol CPMP objectives, exploratory fluid and digital biomarker 
analyses may be conducted on samples and data collected during the study.  
Interim Analyses 
Interim analyses may be conducted for internal decision-making. Unblinding and interim 
analysis details may be specified in the unblinding plan section of the SAP or in a separate 
document. 
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10.
Supporting Documentation and Operational Considerations
Appendix 1: Clinical Laboratory Tests
The master protocol CPMP describes tests that may be performed at additional times noted in the 
SoA for this ISA. This table describes tests unique for ISA OA03.  
Chemistry
Additional Thyroid Tests
Other SST-Regulated Hormones
Other Tests
Cystatin-C
Free Triiodothyronine (FreeT3)
Growth hormone
Amylase
TSH
Total Triiodothyronine (T3)
Insulin-like Growth Factor-1 (IGF-1)
Lipase
Free Thyroxine (FreeT4) 
Prolactin
LY3556050 concentration
Total Thyroxine (T4)
Gastrin
Serum pregnancy test
Glucagon
HbA1c
Insulin
Abbreviations: HbA1c = glycated hemoglobin; SST = somatostatin; TSH = thyroid-stimulating hormone.
Thyroid Safety Follow-Up
TSH
Free Triiodothyronine (FreeT3)
Total Triiodothyronine (T3)
Free Thyroxine (FreeT4) 
Total Thyroxine (T4)
Thyroglobulin
Anti-Thyroglobulin
Anti-Thyroperoxidase Antibodies
Iodine
Abbreviation:  TSH = thyroid-stimulating hormone.
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Appendix 2: Definitions of Reproductive Requirements and 
Contraceptive Guidance
Women
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Woman not of Childbearing Potential (non-WOCBP)
Women in the following categories are not considered WOCBP:

premenarchal

premenopausal female that is infertile due to surgical sterilization, or

postmenopausal.
Surgical sterilization examples include

hysterectomy 

bilateral oophorectomy, or

tubal ligation.  
Postmenopausal is defined as either

a woman at least 40 years of age with an intact uterus, not on hormone therapy, who has 
cessation of menses for at least 1 year without an alternative medical cause, AND a 
follicle-stimulating hormone >40 mIU/mL

a woman 55 or older not on hormone therapy, who has had at least 12 months of 
spontaneous amenorrhea, or

a woman at least 55 years of age with a diagnosis of menopause prior to starting hormone 
replacement therapy.
For individuals with permanent infertility due to an alternate medical cause other than the above, 
(e.g., Müllerian agenesis, androgen insensitivity), investigator discretion should be applied to 
determining study entry.
Note:  Determination can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
Participation in the Study
Women not of childbearing potential and of childbearing potential may participate in this study.
Women not of childbearing potential include those who 

have a congenital anomaly such as Müllerian agenesis 

are infertile due to surgical sterilization, or 

are postmenopausal.  

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At least 6 weeks must have passed after surgical bilateral oophorectomy with or without 
hysterectomy, or after tubal ligation.
Women of childbearing potential must test negative for pregnancy prior to initiation of treatment 
as indicated by a negative serum pregnancy test at the screening visit followed by a negative 
urine pregnancy test within 24 hours prior to exposure.
Women of childbearing potential who are completely abstinent or in a same-sex relationship, as 
part of their preferred and usual lifestyle, must agree to either remain abstinent or stay in a 
same-sex relationship without sexual relationships with males.
All other women of childbearing potential must agree to use 1 highly effective method of 
contraception (less than 1% failure rate), or a combination of 2 effective methods of 
contraception, for the entirety of the study. 
Abstinence or contraception must continue for 3 days after the last dose of intervention.
Acceptable Methods of Contraception
Highly effective methods of contraception (less than 1% failure rate) comprise, but are not 
limited to

combination oral contraceptive pill and mini-pill

implanted or injectable contraceptives

contraceptive patch (only for women <198 pounds or 90 kg)

total abstinence

vasectomy if they are the only sexual partner

fallopian tube implants if confirmed by hysterosalpingogram

combined contraceptive vaginal ring, or 

intrauterine devices. 
Effective methods of contraception comprise but are not limited to

male or female condoms with spermicide

diaphragms with spermicide or cervical sponges

barrier method with use of a spermicide
o
condom with spermicide
o
diaphragm with spermicide, or
o
female condom with spermicide.
Note:  The barrier method must include use of a spermicide (i.e., condom with spermicide, 
diaphragm with spermicide, female condom with spermicide) to be considered effective.  
Not Acceptable Methods of Contraception
Ineffective methods of contraception comprise of

spermicide alone 

immuno-contraceptives

periodic abstinence

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
fertility awareness 
o
calendar method 
o
temperature method 
o
combination of calendar and temperature method
o
cervical mucus, or
o
symptothermal

withdrawal

post coital douche, or

lactational amenorrhea.
Men
Men are not required to use contraception during study participation.
Collection of Pregnancy Information
Male participants with partners who become pregnant
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive LY3556050.
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the investigator will record pregnancy information on the appropriate form and submit it to the 
sponsor within 24 hours of learning of the partner’s pregnancy. 
The female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the sponsor. Generally, the follow-up 
will be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of gestational age, fetal status (presence or absence of 
anomalies) or indication for the procedure. 
Female participants who become pregnant
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a participant's 
pregnancy. 
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, including 
fetal status (presence or absence of anomalies) or indication for the procedure.
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring at 
≥20 weeks gestational age) is always considered to be an SAE and will be reported as such. 

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Any poststudy pregnancy-related SAE considered reasonably related to the study intervention by 
the investigator will be reported to the sponsor as described in the master protocol CPMP 
Section 8.3.4. While the investigator is not obligated to actively seek this information in former 
study participants, he or she may learn of an SAE through spontaneous reporting.
Any female participant who becomes pregnant while participating in the study will be withdrawn 
from the study and will follow the standard discontinuation process.  

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Appendix 3:  Provisions for Changes in Study Conduct During 
Exceptional Circumstances
Implementation of this appendix
The changes to procedures described in this appendix are temporary measures intended to be 
used only during specific time periods as directed by the sponsor.
Exceptional circumstances
Exceptional circumstances are rare events may cause disruptions to the conduct of the study.
Examples include pandemics or natural disasters. These disruptions may limit the ability of the 
investigators, participants, or both to attend on-site visits or to conduct planned study procedures.
Implementing changes under exceptional circumstances
In an exceptional circumstance, after receiving the sponsor’s written approval, sites may 
implement changes if permitted by local regulations. 
Ethical Review Boards (ERBs) and regulatory bodies will be notified as early as possible to 
communicate implementation of changes in study conduct due to exceptional circumstances. To 
protect the safety of study participants, urgent changes may be implemented before 
communication to ERBs and regulatory bodies. Lilly will report all changes as soon as possible 
following implementation. If approval of ERBs, regulatory bodies, or both is required per local 
regulations, the site must retain confirmation of this approval in the study records.
Additional written guidance will be provided by the sponsor in the event written approval is 
granted for changes in study conduct. 
Considerations for making a change
The prevailing consideration for making a change is ensuring the safety of study participants.
Additional important considerations for making a change are

Good Clinical Practice compliance, and

minimization of risk to study integrity. 
Such changes are intended to

mitigate risks of participants missing visits

allow participants to continue safely in the study, and

maintain the data integrity of the study. 
Informed Consent
If these circumstances occur, additional consent from the participant will be obtained, if 
applicable, for:

participation in remote visits

additional study intervention dispensed to a participant during an extended visit window, 
or

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
alternate delivery of study intervention and ancillary supplies, as well as provision for
their personal or medical information required prior to implementation of these 
activities.
Changes in Study Conduct
Changes in study conduct not described in this appendix, or not consistent with applicable local 
regulations, are not allowed.
The following changes in study conduct will not be considered protocol deviations. Missing data 
will be captured as protocol deviations.
Remote visits
In source documents and the CRF, the study site should capture the visit method, with a specific 
explanation for any data missing because of missed in-person site visits. 
Telemedicine:  Telephone or technology-assisted virtual visits, or both, are acceptable to 
complete appropriate assessments. 
Assessments to be completed in this manner include, but are not limited to, individual 
safety follow-up.
Mobile healthcare: Healthcare visits may be performed at locations other than the study 
site (for example, participant’s home) when participants cannot travel to the site due to an 
exceptional circumstance. Such visits will be performed by a mobile healthcare provider. 
Procedures performed at such visits include, but are not limited to, collection of blood 
samples, physical examinations, ECGs, vital signs, intervention accountability and 
compliance, AE collection, and collection of health information.
Other local procedures: Laboratory draws may be done at an alternate location in 
exceptional circumstances.
Regardless of the type of remote visits implemented, the protocol requirements regarding the 
reporting of AEs, SAEs, and product complaints remain unchanged. 
Every effort should be made to enable participants to return to onsite visits as soon as reasonably 
possible, while ensuring the safety of both the participants and the site staff.
Local Laboratory Testing
Local laboratory testing may be conducted in lieu of central laboratory testing. The local 
laboratory must be qualified in accordance with applicable local regulations.
If local testing is used, PK and exploratory biomarker sample collection may not occur.
Investigational Product and Ancillary Supplies (including participant diaries)
When a participant is unable to go to the site to receive study supplies during normal onsite 
visits, the site should work with the sponsor to determine appropriate actions. These actions may 
include:

asking the participant to go to the site and receive study supplies from site staff 
without completion of a full study visit,

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
asking the participant’s designee to go to the site and receive study supplies on a 
participant’s behalf, and

arranging delivery of study supplies.
Alternate delivery of investigational product should be performed in a manner that does not 
compromise treatment blinding and ensures product integrity. 
The existing protocol requirements for product accountability remain unchanged, including 
verification of participant’s receipt of study supplies.
When delivering supplies to a location other than the study site, the investigator, sponsor, or both 
should ensure oversight of the shipping process to ensure accountability and product quality (that 
is, storage conditions maintained and intact packaging upon receipt).
Instructions should be provided to the participant on how to return any unused or completed 
study supplies.
For participants whose visits have extended windows, additional study intervention may need to 
be provided to avoid study intervention interruption and maintain overall integrity of the study.
Adjustments to Visit Windows
Participants should complete the SoA as described in the master protocol CPMP, DSA CPMP(1) 
and this ISA whenever possible and safe to do so. To maximize the possibility that visits are
conducted at the clinical site, the visit windows may be adjusted to minimize missing data and 
preserve the intended conduct of the study. Adjustments to the visit windows will be discussed 
with, and approved by, the sponsor prior to any changes.
Documentation
Changes to study conduct will be documented.
Sites will identify and document the details of how participants, visits types, and conducted 
activities were affected by exceptional circumstances. 
Dispensing and shipment records of intervention and relevant communications, including 
delegation, should be filed with site study records.
Source documents generated at a location other than the study site should be part of the 
investigator’s source documentation and should be transferred to the site in a secure and timely 
manner.
The study site should capture specific explanations for any missing data and other protocol 
deviations in source documents. 
Although protocol deviations may be unavoidable in an exceptional circumstance, 
documentation of protocol deviations and missing data will be important for data analysis and 
reporting.

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Appendix 4: Abbreviations
Term
Definition
BID
twice daily
DSA
disease-state addendum
eGFR
estimated glomerular filtration rate
ERB
Ethical Review Board
FACTS
Fixed and Adaptive Clinical Trial Simulator software tool
ISA
intervention-specific appendix
OA
osteoarthritis
PD
pharmacodynamic
PK
pharmacokinetic
PKPD
pharmacokinetic-pharmacodynamic
PR interval
During an ECG, the period, measured in milliseconds, that extends from the beginning 
of the P wave until the beginning of the QRS complex.
QRS
During an ECG, a combination of the Q wave, R wave and S wave, representing 
ventricular depolarization.
QT
During an ECG, the QT interval is the time from the start of the Q wave to the endo of 
the T wave.
QTcF
QT interval using Fridericia’s correction formula
SST
somatostatin
SSTR
somatostatin receptor
TSH
thyroid-stimulating hormone
WOCBP
woman/women of childbearing potential
WOMAC
Western Ontario and McMaster University Osteoarthritis Index

A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  2 4 - F e b - 2 0 2 1  2 0 : 5 8 : 0 5  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  2 4 - F e b - 2 0 2 1  2 3 : 4 7 : 3 5  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
C CI
P P D
P P D

A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 2 - M a r - 2 0 2 1  0 2 : 0 9 : 1 5  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 2 - M a r - 2 0 2 1  2 2 : 4 1 : 4 3  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
P P D
P P D
C CI

A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 3 - M a r - 2 0 2 1  1 9 : 5 8 : 5 3  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 3 - M a r - 2 0 2 1  1 9 : 5 9 : 0 2  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
P P D
P P D
C CI