A 6-month, Open Label, Randomised, Efficacy Study to Evaluate Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) Inhalation Powder Delivered Once Daily Via the Dry Powder Inhaler ELLIPTA™ Compared With Usual ICS/LABA Maintenance Therapy Delivered by Dry Powder Inhaler in Subjects With Persistent Asthma
Phase: PHASE3
Conditions: Asthma
Sponsor: GlaxoSmithKline

2014N190259_02
&21),'(17,$/
7KH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV
HZA116492
1
'LYLVLRQ:RUOGZLGH'HYHORSPHQW
,QIRUPDWLRQ7\SH3URWRFRO$PHQGPHQW
7LWOH
$PRQWKRSHQODEHOUDQGRPLVHGHIILFDF\VWXG\WRHYDOXDWH
IOXWLFDVRQHIXURDWH))*:YLODQWHURO9,*:
,QKDODWLRQ3RZGHUGHOLYHUHGRQFHGDLO\YLDWKH'U\3RZGHU
,QKDOHU(OOLSWDFRPSDUHGZLWKXVXDO,&6/$%$PDLQWHQDQFH
WKHUDS\GHOLYHUHGE\'U\3RZGHU,QKDOHULQVXEMHFWVZLWK
3HUVLVWHQW$VWKPD
&RPSRXQG1XPEHU
*: *:
'HYHORSPHQW3KDVH
,,,%
(IIHFWLYH'DWH
$35
3URWRFRO$PHQGPHQW1XPEHU
$XWKRU V

&RS\ULJKW WKH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV$OOULJKWVUHVHUYHG
8QDXWKRULVHGFRS\LQJRUXVH RIWKLVLQIRUPDWLRQLVSURKLELWHG

2017N339371_00
33'

2014N190259_02
&21),'(17,$/
7KH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV
HZA116492
2
5HYLVLRQ&KURQRORJ\
*OD[R6PLWK.OLQH
'RFXPHQW1XPEHU
'DWH
9HUVLRQ
1B
)(%
2ULJLQDO
1B
$8*
$PHQGPHQW1R
7KLVSURWRFRODPHQGPHQWKDVEHHQFUHDWHGWRFRUUHFWPLVWDNHVLQWKHZRUGLQJRIWKH
LQKDOHUHUURUVTXHVWLRQQDLUHVIRUWKH(OOLSWD'LVNXVDQG7XUEXKDOHULQKDOHUVZKLFK
DUHLQFOXGHGLQ6HFWLRQRIWKHSURWRFRO$OOUHIHUHQFHVWRµ7\SH$HUURUV¶DQG
µRYHUDOOHUURUV¶ZLWKLQWKHSURWRFROKDYHEHHQFKDQJHGWRµFULWLFDO¶DQGµQRQFULWLFDO¶
HUURUVUHVSHFWLYHO\IRUFRQVLVWHQF\ZLWKWKHLQKDOHUHUURUVTXHVWLRQQDLUHZRUNVKHHWV
6WRUDJHFRQGLWLRQLQVWUXFWLRQVIRU6HUHWLGH IOXWLFDVRQHSURSLRQDWHVDOPHWHUROLQ
6HFWLRQKDYHEHHQDPHQGHG
7KHZRUGLQJIRUWKHUHFRPPHQGHGQXPEHURIVSLURPHWU\HIIRUWVKDVEHHQUHYLVHG
1HZWH[WKDVEHHQLQFOXGHGZLWKUHJDUGVWRLQYHVWLJDWLRQDOSURGXFWPDOIXQFWLRQLQ
6HFWLRQ
7KHVHFRQGDU\PHGLFDOPRQLWRUFRQWDFWLQIRUPDWLRQKDVEHHQUHYLVHGWRLQFOXGHDQHZ
VWXG\SK\VLFLDQ
2WKHUPLQRUFRUUHFWLRQVDQGHGLWVKDYHEHHQPDGH
1B
$35
$PHQGPHQW1R
7KLVDPHQGPHQWKDVEHHQZULWWHQSULPDULO\WRDOORZWKHDGGLWLRQRIDQHZ
FRXQWU\FRXQWULHVWRWKHVWXG\7KLVLQFOXGHV
!
5HPRYLQJUHIHUHQFHWR)UDQFHXQOHVVVSHFLILFDOO\UHTXLUHG
!
$PHQGLQJWH[WWRPDNHODQJXDJHPRUHDSSOLFDEOHWRSDUWLFLSDWLQJFRXQWULHV
!
8SGDWLQJWKHQXPEHURIVLWHV
!
'HILQLQJSHUPLWWHGµXVXDO,&6/$%$FRPELQDWLRQV¶
7KHHQGSRLQWDVVRFLDWHGZLWK,QKDOHU&RUUHFW8VHKDVEHHQIXUWKHUGHILQHG
7KHREMHFWLYHDQGDVVRFLDWHGHQGSRLQWRIDGKHUHQFHZLWKVWXG\PHGLFDWLRQKDVEHHQ
DPHQGHGWRFRPSOLDQFH ZLWKVWXG\PHGLFDWLRQ
0HSROL]XPDE1XFDODKDVEHHQDGGHGDVDSURKLELWHGPHGLFDWLRQDWVFUHHQLQJDQG
GXULQJWKHVWXG\
7KHRSWLRQWRUHVFUHHQDSDWLHQWIROORZLQJDSSURYDOE\WKHPHGLFDOPRQLWRUKDVEHHQ
DGGHG

2017N339371_00

2014N190259_02
&21),'(17,$/
7KH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV
HZA116492
3
7KHVHFWLRQGHVFULELQJSODQQHGGRVHDGMXVWPHQWVKDVEHHQXSGDWHGWRFODULI\WKDWGRVH
LQFUHDVHV DUHSHUPLWWHGEXWVZLWFKLQJEHWZHHQWUHDWPHQWVLVQRW SHUPLWWHG LQDFFRUGDQFH
ZLWKWKHLQWHQWLRQRIWKHSURWRFRO
,WKDVEHHQFODULILHGWKDW*6.ZLOOQRWSURYLGHWUHDWPHQWIROORZLQJWKHVWXG\
7KH7	(WDEOHKDVEHHQXSGDWHGWRUHIOHFWWKDW6FUHHQLQJ9LVLWDQG:LWKGUDZDO9LVLW
VKRXOGEHORJJHGRQ5$0261*7KLVZDVSUHYLRXVO\RPLWWHGLQHUURU
7KHGHVFULSWLRQRIWKH3HU3URWRFRO3RSXODWLRQKDVEHHQXSGDWHGWRUHIOHFWWHUPLQRORJ\
QRZXVHGDVVWDQGDUGDW*6.
2WKHUPLQRUFRUUHFWLRQVDQGHGLWVKDYH EHHQPDGH

2017N339371_00


2017N339371_00
33'
33'

2014N190259_02
&21),'(17,$/
HZA116492
5
0(',&$/021,7256321625,1)250$7,213$*(
0HGLFDO0RQLWRU6$(&RQWDFW,QIRUPDWLRQ
Role
1DPH
'D\7LPH3KRQH1XPEHU
DQGHPDLODGGUHVV
$IWHUKRXUV
3KRQH&HOO
3DJHU1XPEHU
)D[
1XPEHU
6LWH$GGUHVV
3ULPDU\
0HGLFDO
0RQLWRU
&OLQLFDO
'HYHORSPHQW
3K\VLFLDQ
5'
5HVSLUDWRU\
5	'
3KRQH
(PDLO
*OD[R6PLWK.OLQH
5HVHDUFK	
'HYHORSPHQW
/LPLWHG
,URQ%ULGJH
5RDG
6WRFNOH\3DUN
:HVW8[EULGJH
0LGGOHVH[8%
%78.
6HFRQGDU\
0HGLFDO
0RQLWRU

3KRQH
(PDLO
*OD[R6PLWK.OLQH
6WRFNOH\3DUN
:HVW
,URQEULGJH
5RDG
8[EULGJH
0LGGOHVH[8%
%7
6$(
FRRUGLQDWRU


2SHUDWLRQV
DQG6FLHQFH
/HDG
3KRQH 
(PDLO
*6.)UDQFH
5RXWHGH
9HUVDLOOHV0DUO\
OH5RL
)UDQFH
6SRQVRU/HJDO5HJLVWHUHG$GGUHVV
*OD[R6PLWK.OLQH5HVHDUFK	'HYHORSPHQW/LPLWHG
*UHDW:HVW5RDG
%UHQWIRUG
0LGGOHVH[7:*6
8.
6SRQVRU&RQWDFW$GGUHVV
*OD[R6PLWK.OLQH5HVHDUFK	'HYHORSPHQW/LPLWHG
,URQ%ULGJH5RDG
6WRFNOH\3DUN:HVW8[EULGJH0LGGOHVH[8%%88.
7HOHSKRQH


2017N339371_00
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'

2014N190259_02
&21),'(17,$/
HZA116492
6
6SRQVRU6HULRXV$GYHUVH(YHQWV6$(&RQWDFW,QIRUPDWLRQ
&DVH0DQDJHPHQW*URXS*&63
6WRFNOH\3DUN:HVW8[EULGJH0LGGOHVH[8%%88.
(PDLO
)D[
5HJXODWRU\$JHQF\,GHQWLI\LQJ1XPEHUV(XGUD&71R

2017N339371_00
33'
33'

2014N190259_02
&21),'(17,$/
HZA116492
7
,19(67,*$72535272&2/$*5((0(173$*(
)RUSURWRFROQXPEHU +=$
, FRQILUPDJUHHPHQWWRFRQGXFWWKHVWXG\LQFRPSOLDQFHZLWKWKHSURWRFRODVDPHQGHGE\
WKLVSURWRFRODPHQGPHQW
,DFNQRZOHGJHWKDW,DPUHVSRQVLEOHIRURYHUDOOVWXG\FRQGXFW,DJUHHWRSHUVRQDOO\
FRQGXFWRUVXSHUYLVHWKHGHVFULEHGVWXG\
,DJUHHWRHQVXUHWKDWDOODVVRFLDWHVFROOHDJXHVDQGHPSOR\HHVDVVLVWLQJLQWKHFRQGXFWRI
WKHVWXG\DUHLQIRUPHGDERXWWKHLUREOLJDWLRQV0HFKDQLVPVDUHLQSODFHWRHQVXUHWKDWVLWH
VWDIIUHFHLYHVWKHDSSURSULDWHLQIRUPDWLRQWKURXJKRXWWKHVWXG\
,QYHVWLJDWRU1DPH
,QYHVWLJDWRU$GGUHVV
,QYHVWLJDWRU3KRQH1XPEHU
,QYHVWLJDWRU6LJQDWXUH
'DWH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
8
7$%/(2)&217(176
3$*(
1.
PROTOCOL SYNOPSIS FOR STUDY HZA116492...............................................11
2.
INTRODUCTION....................................................................................................16
2.1.
Study Rationale ..........................................................................................16
2.2.
Brief Background ........................................................................................17
3.
OBJECTIVE(S) AND ENDPOINT(S) ......................................................................18
4.
STUDY DESIGN ....................................................................................................21
4.1.
Overall Design ............................................................................................21
4.2.
Treatment arms and duration......................................................................24
4.3.
Type and Number of Subjects.....................................................................24
4.4.
Design Justification.....................................................................................25
4.5.
Dose Justification........................................................................................25
4.6.
Benefit: Risk Assessment ...........................................................................25
4.6.1.
Risk Assessment .........................................................................26
4.6.1.1.
Benefit Assessment....................................................30
4.6.2.
Overall Benefit: Risk Conclusion..................................................30
5.
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA .............30
5.1.
Inclusion Criteria.........................................................................................30
5.2.
Exclusion Criteria........................................................................................32
5.3.
Screening/Baseline/Failures .......................................................................33
5.4.
Withdrawal/Stopping Criteria.......................................................................34
5.4.1.
Subjects Lost to Follow-up...........................................................34
5.4.2.
Subject Withdrawal by Investigator or Self-withdrawal .................34
5.4.3.
Liver Chemistry Stopping Criteria ................................................35
5.4.3.1.
Study Treatment Restart or Rechallenge....................36
5.4.4.
QTc Stopping Criteria ..................................................................36
5.5.
Subject and Study Completion....................................................................37
6.
STUDY TREATMENT ............................................................................................37
6.1.
Investigational Product and Other Study Treatment....................................37
6.2.
Medical Devices..........................................................................................38
6.3.
Treatment Assignment................................................................................39
6.4.
Planned Dose Adjustments.........................................................................40
6.5.
Blinding.......................................................................................................40
6.6.
Packaging and Labeling..............................................................................40
6.7.
Preparation/Handling/Storage/Accountability..............................................41
6.8.
Investigational Product Malfunction.............................................................41
6.9.
Compliance with Study Treatment Administration.......................................42
6.10.
Treatment of Study Treatment Overdose....................................................42
6.11.
Treatment after the End of the Study ..........................................................43
6.12.
Concomitant Medications and Non-Drug Therapies....................................43
6.12.1.
Permitted Medications and Non-Drug Therapies..........................43
6.12.2.
Prohibited Medications and Non-Drug Therapies.........................43
7.
STUDY ASSESSMENTS AND PROCEDURES .....................................................44

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
9
7.1.
Time and Events Table...............................................................................45
7.2.
Screening and Critical Baseline Assessments ............................................47
7.3.
Efficacy.......................................................................................................47
7.3.1.
Inhaler Correct Use Assessment .................................................47
7.3.2.
Trough (pre-dose) FEV1 assessment ..........................................50
7.3.3.
Questionnaires ............................................................................51
7.3.3.1.
Asthma Control Test (ACT) ........................................51
7.3.3.2.
Asthma Quality of Life Questionnaire (AQLQ-S).........51
7.3.3.3.
EuroQol Questionnaire (EQ-5D)-5 Level ....................51
7.3.3.4.
Medication Adherence Report Scale for 
Asthma (MARS-A)......................................................51
7.3.3.5.
Patients Satisfaction and Preference with the 
device (PASAP Questionnaire)...................................52
7.4.
Safety .........................................................................................................52
7.4.1.
Adverse Events (AE), Adverse Drug Reactions (ADRs) 
and Serious Adverse Events (SAEs)............................................52
7.4.1.1.
Time period and Frequency for collecting non 
serious ADRs and SAE information............................53
7.4.1.2.
Method of Detecting non serious ADRs and 
SAEs ..........................................................................53
7.4.1.3.
Follow-up of non serious ADRs and SAEs..................54
7.4.1.4.
Cardiovascular and Death Events ..............................54
7.4.1.5.
Disease-Related Events and/or Disease-
Related Outcomes Not Qualifying as SAEs ................54
7.4.1.6.
Regulatory Reporting Requirements for SAEs............54
7.4.2.
Pregnancy ...................................................................................55
7.4.3.
Medical Device Incidents (Including Malfunctions).......................55
7.4.4.
Physical Exams ...........................................................................55
7.4.5.
Vital Signs....................................................................................55
7.4.6.
Electrocardiogram (ECG).............................................................55
7.4.7.
Clinical Safety Laboratory Assessments ......................................56
7.5.
Genetics .....................................................................................................56
8.
DATA MANAGEMENT ...........................................................................................56
9.
STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................56
9.1.
Hypotheses.................................................................................................56
9.2.
Sample Size Considerations.......................................................................57
9.2.1.
Sample Size Assumptions ...........................................................57
9.2.2.
Sample Size Sensitivity................................................................57
9.2.3.
Sample Size Re-estimation or Adjustment...................................58
9.3.
Data Analysis Considerations .....................................................................58
9.3.1.
Analysis Populations....................................................................58
9.3.2.
Interim Analysis ...........................................................................58
9.4.
Key Elements of Analysis Plan ...................................................................58
9.4.1.
Primary Analyses.........................................................................60
9.4.2.
Secondary Analyses ....................................................................63
9.4.3.
Other Analyses ............................................................................64
10. STUDY GOVERNANCE CONSIDERATIONS........................................................67
10.1.
Posting of Information on Publicly Available Clinical Trial Registers............67

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
10
10.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................67
10.3.
Quality Control (Study Monitoring) ..............................................................68
10.4.
Quality Assurance.......................................................................................68
10.5.
Study and Site Closure ...............................................................................68
10.6.
Records Retention......................................................................................69
10.7.
Provision of Study Results to Investigators, Posting of Information 
on Publically Available Clinical Trials Registers and Publication .................69
11. REFERENCES.......................................................................................................71
12. APPENDICES........................................................................................................73
12.1.
Appendix 1: Abbreviation and Trademarks .................................................73
12.2.
Appendix 2: Study Schematic .....................................................................76
12.3.
Appendix 3: Questionnaires........................................................................77
12.4.
Appendix 4: Liver Chemistry Stopping and Follow-up Criteria.....................80
12.5.
Appendix 5: Definition of and Procedures for Recording, Evaluating, 
Follow-Up and Reporting of Adverse Events...............................................83
12.5.1.
Definition of Adverse Events and ADRs.......................................83
12.5.2.
Definition of Serious Adverse Events...........................................84
12.5.3.
Definition of Cardiovascular Events .............................................86
12.5.4.
Recording of AEs (ADRs) and SAEs............................................86
12.5.5.
Evaluating AEs (ADRs) and SAEs ...............................................87
12.5.6.
Reporting of SAEs to GSK...........................................................88
12.6.
Appendix 6: Genetic Research ...................................................................89
12.7.
Appendix 7: Collection of Pregnancy Information........................................92
12.8.
Appendix 8: Protocol Changes....................................................................93

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
11

35272&2/6<1236,6)25678'< +=$
5DWLRQDOH
7KHSLYRWDOSKDVH,,,VWXGLHVZHUHNH\WRGHPRQVWUDWHWKHVDIHW\DQGHIILFDF\RI
)OXWLFDVRQH)XURDWH9LODQWHUROLQDVWKPD+RZHYHULWLVLQFUHDVLQJO\DFNQRZOHGJHGWKDW
UDQGRPLVHGFOLQLFDOWULDOVE\GHILQLWLRQWHQG WREHKLJKO\FRQWUROOHGDQGHQURODPRUH
KLJKO\VHOHFWHGSDWLHQWSRSXODWLRQWKDQLVH[SHFWHGWREHSUHVFULEHGWKHPHGLFDWLRQSRVW
DSSURYDO7KHQHHGIRUGDWDLQDPRUHUHSUHVHQWDWLYHSRSXODWLRQLQDFORVHWRµUHDOZRUOG¶
VHWWLQJLVLQFUHDVLQJO\EHLQJUHFRJQLVHGDVLPSRUWDQWWRFRPSOHPHQWSLYRWDOSKDVH,,,
VDIHW\DQGHIILFDF\VWXGLHVLQRUGHUWRHVWDEOLVKWKHEHQHILWVDQGWKHUHIRUHWKHYDOXHRID
PHGLFDWLRQLQWKHFRQWH[WRIFOLQLFDOSUDFWLFH
0RUHRYHUGRXEOHEOLQGFRPSDULVRQRIRQFHGDLO\WRWZLFHGDLO\PHGLFLQHVZKLOH
LPSRUWDQWIRUDVVHVVLQJHIILFDF\UHPRYHVDSRWHQWLDOVRXUFHRIGLIIHUHQFHLQHIIHFWLYHQHVV
GHULYHGIURPSDWLHQWEHKDYLRXUDQGH[SHULHQFH*OD[R6PLWK.OLQH*6.KDVREVHUYHGDQ
LQFUHDVLQJGHPDQGIURPSD\HUVZKRPDNHUHLPEXUVHPHQWDQGSROLF\GHFLVLRQVIRUGDWD
WKDWHQDEOHVWKHHYDOXDWLRQRIDGUXJ
VHIIHFWLYHQHVVDQGLPSDFWRQWKHKHDOWKFDUHV\VWHP
DWODXQFKHJHIIHFWLYHQHVVGDWDIURPDVHWWLQJFORVHWR
UHDOZRUOG
LQDGGLWLRQWR
WUDGLWLRQDOUDQGRPLVHGFOLQLFDOVWXGLHV
7KLVRSHQODEHOUDQGRPLVHGFOLQLFDOVWXG\ZLOOHYDOXDWHWKHHIILFDF\DQGVDIHW\RI))9,
,QKDODWLRQ3RZGHU))PFJ9,PFJRU))PFJ9,PFJ FRPSDUHGZLWKWZR
IL[HGFRPELQDWLRQV,&6/$%$,QKDOHG&RUWLFRVWHURLGV/RQJ$FWLQJ%HWD$JRQLVWV
LQKDODWLRQSRZGHUVIOXWLFDVRQHSURSLRQDWHVDOPHWHURO)36DQGEXGHVRQLGHIRUPRWHURO
%8')IRUDVWKPDPDLQWHQDQFHWKHUDS\LQD³FORVHWRUHDOOLIH´PDQQHULQSULPDU\
FDUHDQGLQUHVSLUDWRU\VSHFLDOLVWFDUHUHVHDUFKVLWHV))9,ZLOOEHDGPLQLVWHUHGRQFH
GDLO\4'YLD(OOLSWDDQG)36RU%8')WZLFHGDLO\%,'YLD'LVNXV DQG
7XUEXKDOHUUHVSHFWLYHO\
2EMHFWLYHV(QGSRLQWV
Objectives
Endpoints
Primary
!
7RFRPSDUHWKHHIILFDF\RI))9,
PFJPFJRU))PFJPFJ
ZLWKXVXDOIL[HGFRPELQDWLRQV
,&6/$%$IRUDVWKPDPDLQWHQDQFH
WKHUDS\DW:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQWKH$VWKPD
&RQWURO7HVW$&7WRWDOVFRUHDW:HHN
9LVLW
Secondary
!
7RDVVHVVHIIHFWRI))9,RQDVWKPD
FRQWUROFRPSDUHGZLWKXVXDO,&6/$%$
IL[HGFRPELQDWLRQDW:HHN9LVLW
!
7RDVVHVV(//,37$ LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXVDQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
!
&KDQJHIURPEDVHOLQHLQ$&7VFRUHDW
:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWV ZLWKFRUUHFWXVH
RIGHYLFHGHILQHGDVQRWPDNLQJDQ\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
12
Objectives
Endpoints
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
FULWLFDOHUURURUQRQFULWLFDOHUURU DW
:HHN9LVLWDQGDW:HHN9LVLW
LQGHSHQGHQWO\RIWKHXVHDW:HHN
9LVLW
Other
7RDVVHVVHIIHFWRI))9,RQWURXJKSUH
GRVH)(9FRPSDUHGZLWKXVXDO
,&6/$%$IL[HGFRPELQDWLRQDW:HHN
9LVLW
7RDVVHVVWKHHIIHFWRI))9,RQUHVSRQVHWR
WUHDWPHQWDW:HHN9LVLWDQG:HHN
9LVLW
7RDVVHVVWKHFRPSOLDQFHZLWKVWXG\
PHGLFDWLRQ DQGVHOIUHSRUWHGDGKHUHQFHWR
VWXG\PHGLFDWLRQ DW:HHN9LVLWDQG
:HHN9LVLW
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQRYHUWKHVWXG\SHULRG
&KDQJHIURPEDVHOLQHLQWURXJKSUHGRVH
)(9DW:HHN9LVLW
$&7VFRUHRUSRLQWLQFUHDVHIURP
EDVHOLQHLQ$&7DW:HHN9LVLWDQG
:HHN9LVLW1RWH$SRLQWLQFUHDVH
LQ$&7WRWDOVFRUHZDVVXJJHVWHGDVWKH
0LQLPDO&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]@
$&7VFRUHDW:HHN9LVLWDQG
:HHN9LVLW
&KDQJHIURPEDVHOLQHLQLQGLYLGXDOTXHVWLRQ
VFRUHVIRU$&7DW:HHNV
!
&RPSOLDQFHZLWKVWXG\PHGLFDWLRQIURP
UDQGRPLVDWLRQ 'D\  WR :HHN 
9LVLW  IURP :HHN  9LVLW  WR
:HHN

9LVLW

DQG
IURP
UDQGRPLVDWLRQ 'D\  WR :HHN 
9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ $GKHUHQFH 5HSRUW 6FDOH
IRU
DVWKPD
DW
WKH
UDQGRPLVDWLRQ
'D\:HHN9LVLWDQG:HHN
9LVLW
1XPEHURIVXEMHFW ZLWKDWOHDVWVHYHUH
DVWKPDH[DFHUEDWLRQQXPEHURIVHYHUH
DVWKPDH[DFHUEDWLRQDQGDQQXDOVHYHUH
H[DFHUEDWLRQUDWHRYHUWKHVWXG\SHULRG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
13
Objectives
Endpoints
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIHDW:HHN9LVLW
7RDVVHVV3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH
DVVHVVPHQWZLWKGLIIHUHQWLQKDOHUV DW
:HHN9LVLW
7RHYDOXDWHWKH6DIHW\RI))9,FRPSDUHG
ZLWKXVXDO,&6/$%$)36DQG%XG)
&KDQJH IURP EDVHOLQH LQ WRWDO VFRUH DQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUHDW:HHN
9LVLW
$Q LQFUHDVH IURP EDVHOLQH RI   LQ
$4/4VWRWDOVFRUHDW:HHN9LVLW
$Q LQFUHDVH IURP EDVHOLQH RI   LQ
$4/4V HQYLURQPHQWDO VWLPXOL GRPDLQ
VFRUHDW:HHN9LVLW
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVHIURPEDVHOLQHRI LQ$4/46
,QGLYLGXDOGRPDLQVFRUHVDW:HHN9LVLW

&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
+HDOWK
VWDWXV
XVLQJ
WKH
(XUR4RO
4XHVWLRQQDLUH (4' DW :HHN 
9LVLW
6FRUH RI 3$6$3 4XHVWLRQQDLUH 3DWLHQW
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN
9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
)UHTXHQF\ DQG W\SH RI VHULRXV
DGYHUVHHYHQWV
)UHTXHQF\DQGW\SHRIQRQVHULRXV
DGYHUVH GUXJ UHDFWLRQV UHODWHG WR
WUHDWPHQW
$VHYHUHDVWKPDH[DFHUEDWLRQZLOOEHGHILQHGDVGHWHULRUDWLRQRIDVWKPDUHTXLULQJWKH
XVHRIV\VWHPLFFRUWLFRVWHURLGV WDEOHWVVXVSHQVLRQRULQMHFWLRQIRUDWOHDVWGD\VRUDQ
LQSDWLHQW KRVSLWDOLVDWLRQ RU HPHUJHQF\ GHSDUWPHQW YLVLW GXH WR DVWKPD WKDW UHTXLUHG
V\VWHPLFFRUWLFRVWHURLGV 
1RWHVGHILQLQJHQGSRLQWV
 &RQWDFWV ZLWK D GRFWRU RU KRVSLWDOLVDWLRQ DUH GHILQHG DV H[DFHUEDWLRQUHODWHG
FRQWDFWV LI WKHVH FRQWDFWV ZHUH D GLUHFW UHVXOW RI DQ DFXWH ZRUVHQLQJ RI DVWKPD
V\PSWRPV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
14
 $SUHVFULSWLRQRIV\VWHPLFFRUWLFRVWHURLGLVGHILQHGDVH[DFHUEDWLRQUHODWHGLIWKH
UHDVRQWKHGUXJZDVJLYHQLQZKROHRULQSDUWZDVWRWUHDWDQDFXWHZRUVHQLQJRI
DVWKPDV\PSWRPV
 ([DFHUEDWLRQUHODWHGKRVSLWDOLVDWLRQLQFOXGHVKRVSLWDOLVDWLRQWKDWLVSURORQJHG DVD
UHVXOWRIDQDVWKPDH[DFHUEDWLRQ
2YHUDOO'HVLJQ
7KLVLVD3KDVH,,,EPXOWLFHQWUHUDQGRPLVHGRSHQODEHOSDUDOOHOJURXSVWXG\SHUIRUPHG
LQVXEMHFWVLQSULPDU\FDUHDQGLQUHVSLUDWRU\VSHFLDOLVWFDUHUHVHDUFKVLWHV ZKRKDYHD
GLDJQRVLVRIDVWKPDDQG UHJXODUWUHDWPHQWIRU DVWKPD
$SSUR[LPDWHO\DVWKPDWLFVXEMHFWVZKRDUHWDNLQJDQLQKDOHGFRUWLFRVWHURLG,&6
DORQHZLWKRXWDQ\RWKHUFRQWUROOHUWUHDWPHQWZLOOEHUDQGRPLVHGLQDUDWLRWRUHFHLYH
HLWKHU))9,))9,PFJPFJRU))9,PFJPFJRQFHGDLO\RURQH
,&6/$%$ LQKDODWLRQSRZGHUWZLFHGDLO\IRUDVWKPDPDLQWHQDQFHWKHUDS\
$VPXFKDVSRVVLEOHHQUROPHQWRIVXEMHFWVVKRXOGEHSHUIRUPHGDWDFRQVWDQWDFFUXDOUDWH
WKURXJKRXWDIXOO\HDULQRUGHUWRPLQLPL]HDVHDVRQDOLW\ELDV
6XEMHFWV ZLOOYLVLWWKHLQYHVWLJDWRUVLWHDPLQLPXPRIWLPHVDVSHUSURWRFRORYHUD
PRQWKSHULRGZKLOHSDUWLFLSDWLQJLQWKHVWXG\7KHILUVWYLVLWZLOOEH9LVLW6FUHHQLQJ
9LVLWZKLFKFDQWDNHSODFHEHWZHHQ'D\DQG'D\$W9LVLWVXLWDEOHVXEMHFWVZLOO
EHFRQVHQWHG7KHVHFRQGYLVLWZLOOEH9LVLW'D\5DQGRPLVDWLRQ9LVLWZKHUH
VXEMHFWVZKRPHHWDOORIWKH,QFOXVLRQ&ULWHULDDQGQRQHRIWKH([FOXVLRQ&ULWHULDZLOOEH
UDQGRPLVHG9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLV XVXDO
DVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG9LVLWDUHFRPELQHGWKHQWKLV
YLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEHFROOHFWHGDWWKLVYLVLW
$W9LVLW'D\VXEMHFWZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4
'DQG0$56$TXHVWLRQQDLUHV%DVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.$WOHDVWWKUHHYDOLGDVVHVVPHQWV
VKRXOGEHSHUIRUPHGZLWKUHJLVWUDWLRQRIWKHEHVWYDOXH2QWKHPRUQLQJRI9LVLW
VXEMHFWVZLOOQRWWDNHWKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOO
EHVWRSSHGKRXUVEHIRUHEDVHOLQHVSLURPHWU\
6XEMHFWVZLOOVHOIDGPLQLVWHUWKHLUILUVWGRVHRIVWXG\GUXJDWWKHLQYHVWLJDWRUVLWHDW9LVLW
RUWKHFRPELQHG9LVLWDQG9LVLWLIDSSURSULDWHXQGHUVXSHUYLVLRQRIWKH
LQYHVWLJDWRURUVXLWDEO\TXDOLILHGGHVLJQHH
7KHUHDIWHUHDFKVXEMHFWUDQGRPLVHGLQWRWKH))9,DUPZLOOEHLQVWUXFWHGWRVHOI
DGPLQLVWHURQHLQKDODWLRQZLWK(OOLSWDLQKDOHUHDFKGD\DWWKHVDPHWLPHRIWKHGD\DWD
WLPHWKDWLVFRQYHQLHQWIRUWKHVXEMHFW(DFKVXEMHFWZLOOEHDGYLVHGWRDGKHUHWR))9,
GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\7KHLQYHVWLJDWRUPD\DGMXVWWKHGRVHRI))9,
DFFRUGLQJWRWKHVXEMHFW¶VUHVSRQVH'RVHDGMXVWPHQWLVDOORZHGDQGLVQRWFRQVLGHUHGDV
DWUHDWPHQWIDLOXUHLQDFFRUGDQFHZLWKWUHDWPHQWIDLOXUHGHILQLWLRQ
,QDGGLWLRQHDFKVXEMHFWZKRVH))9,(OOLSWDIRUDVWKPDPDLQWHQDQFHWKHUDS\LV
LQLWLDWHGDW9LVLWZLOOEHDVNHGWRUHDGWKHLQIRUPDWLRQOHDIOHWDQG ZLOOEHLQVWUXFWHGE\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
15
WKHLQYHVWLJDWRURQWKHSURSHUXVHRI(OOLSWD(DFKVXEMHFWZKRVHXVXDO,&6/$%$'3,
'LVNXVRU7XUEXKDOHUIRUDVWKPDPDLQWHQDQFHWKHUDS\LVLQLWLDWHGDW9LVLWZLOOIROORZ
WKHVDPHSURFHGXUHUHDGLQJRIWKHLQIRUPDWLRQOHDIOHWGHPRQVWUDWLRQRIWKHSURSHUXVHRI
WKHLQKDOHUVE\WKH,QYHVWLJDWRUDQGWKHFRUUHFWGRVLQJ7KLVZLOOEHIROORZHGE\DQ
LQKDODWLRQGHPRQVWUDWLRQE\WKHSDWLHQW$Q\FULWLFDOHUURUGHILQHGDVDQHUURUWKDWLV
PRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJLQKDOHGDQGRUQRQFULWLFDO
HUURUZLOOEHUHJLVWHUHGE\WKH,QYHVWLJDWRU
5DQGRPLVDWLRQDWWKLVYLVLWZLOOEHSHUIRUPHGRQDEDVLVWRWKH))9,IL[HGGRVH
FRPELQDWLRQGHOLYHUHGYLD(OOLSWD RUWKHLQLWLDWLRQZLWKXVXDO,&6/$%$LQKDODWLRQ
SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\
$W:HHN 9LVLWDQGDW:HHN9LVLWVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXW
ZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQVHULRXVDGYHUVH
GUXJUHDFWLRQV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJFULWLFDODQG
QRQFULWLFDOHUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRIVWXG\
GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQ
FDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWDWURXJKSUHGRVH)(9ZLOOEHDVVHVVHG
E\WKH,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.DQGVXEMHFWVZLOODOVREH
LQWHUYLHZHGDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ
±VHULRXVDGYHUVHGUXJUHDFWLRQV)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREH
UHPLQGHGDERXWWKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KHILQDO9LVLWZLOORFFXU DW:HHN7KH$&7$4/46(4'DQG0$56$
TXHVWLRQQDLUHVZLOOEHFRQGXFWHGDWWKLVYLVLWDQGFULWLFDODQGQRQFULWLFDOHUURUVZLWK
LQKDOHUZLOOEHUHFRUGHG IROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWVXEMHFWVZLOODOVREHLQWHUYLHZHGDERXW
ZKHWKHUWKH\KDGH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJ
UHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKH
VDPHWLPHRIWKHGD\DV9LVLW
$OWKRXJKDWOHDVWIRUPDOVFKHGXOHGYLVLWVDQGSKRQHFDOOVDUHSODQQHGIRUWKLVVWXG\
DVSHUWKH7LPHDQG(YHQWV7DEOHVXEMHFWVVKRXOGFRQWLQXHWRYLVLWWKHLUSK\VLFLDQIRU
DQ\URXWLQHVWDQGDUGRIFDUHYLVLWVDVSHUQRUPDOFOLQLFDOSUDFWLFH $Q(DUO\:LWKGUDZDO
9LVLWVKRXOGEHSHUIRUPHG LQFDVHRIHDUO\ZLWKGUDZDORIWKHVXEMHFWIURPWKHVWXG\DV
SHUWKH7LPHDQG(YHQWV7DEOH
7UHDWPHQW$UPVDQG'XUDWLRQ
7ZRWUHDWPHQWDUPVRQH))9,DUP))9,PFJPFJRU))9,PFJPFJ
RQFHGDLO\DQGRQHDUP,&6/$%$FRPELQDWLRQWKHUDS\LQLQKDODWLRQSRZGHUWZLFH
GDLO\)36PFJPFJRUPFJPFJRU%8')PFJPFJRU

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
16
PFJPFJDVGHFLGHGE\WKHLQYHVWLJDWRU 7KHWRWDOGXUDWLRQRIVXEMHFWSDUWLFLSDWLRQ
ZLOOEHDSSUR[LPDWHO\PRQWKVZHHNV
7\SHDQG1XPEHURI6XEMHFWV
6XEMHFWVZLWKGRFXPHQWHGSK\VLFLDQ¶VGLDJQRVLVRIDVWKPD\HDUXQVDWLVIDFWRULO\
FRQWUROOHGDVWKPD$&7WUHDWHGE\,&6DORQHDQGLQWHQGHGWREHWUHDWHGE\
,&6/$%$PDLQWHQDQFHWKHUDS\
)UDQFH2QO\$VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\RQO\ LIHLWKHUDIILOLDWHG
WRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\ VWXG\FHQWHUVZLOOEHUHTXLUHGWRKDYHDWRWDO
QXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJD VFUHHQIDLOXUHUDWHDSSUR[LPDWHO\VXEMHFWVZLOOKDYHWREHVFUHHQHG
$QDO\VLV
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQHLQWKH$&7WRWDOVFRUH
DVVHVVHGDW:HHN9LVLW7KHSULPDU\VHWRIDQDO\VLVLVWKH,77SRSXODWLRQ
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHWZRVLGHGQRPLQDO
OHYHORIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,
WR,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
(YHQWKRXJKWKLVVWXG\LVRSHQODEHOWKHWHDPZLOOH[SORUHZD\VWRHQVXUHVWXG\EOLQGLV
PDLQWDLQHGGXULQJUHYLHZRIWKHGDWDDQGSUHSURJUDPPLQJDFWLYLWLHVSULRUWRGDWDEDVH
ORFN0RUHLQIRUPDWLRQZLOOEHSURYLGHGLQWKH5$3

,1752'8&7,21

6WXG\5DWLRQDOH
,QKDOHGFRUWLFRVWHURLGV,&6DUHFRQVLGHUHGWKHPRVWHIIHFWLYHDQWLLQIODPPDWRU\
WUHDWPHQWVIRUDOOVHYHULWLHVRISHUVLVWHQWDVWKPD7KLVRSHQODEHOUDQGRPLVHGFOLQLFDO
VWXG\ZLOOHYDOXDWHWKHHIILFDF\DQGVDIHW\RIIOXWLFDVRQHIXURDWH))YLODQWHURO 9,
,QKDODWLRQ3RZGHUFRPSDUHGZLWKQRPLQDWHGH[LVWLQJIL[HGFRPELQDWLRQV,&6/$%$
,QKDOHG&RUWLFRVWHURLGV/RQJ$FWLQJ%HWD$JRQLVWVLQKDODWLRQSRZGHUV
)OXWLFDVRQHIXURDWH))LVDJOXFRFRUWLFRLGGHYHORSHGIRUXVHDVDRQFHGDLO\LQKDOHG
WUHDWPHQWIRUDVWKPD 9LODQWHUROLVDQRUDOO\LQKDOHGORQJDFWLQJDJRQLVWRIWKHEHWD
DGUHQRFHSWRU/$%$DQGKDVEHHQDOVRGHYHORSHGIRUXVHLQFRPELQDWLRQZLWK,&6DVD
RQFHGDLO\PDLQWHQDQFHWUHDWPHQWRIDVWKPD
7KHSLYRWDOSKDVH,,,VWXGLHVGHPRQVWUDWHGWKHVDIHW\DQGHIILFDF\RI))9,+RZHYHULW
LVLQFUHDVLQJO\DFNQRZOHGJHGWKDWUDQGRPLVHGFOLQLFDOWULDOVE\GHILQLWLRQWHQGWREH
KLJKO\FRQWUROOHGDQGHQURODPRUHKLJKO\VHOHFWHGSDWLHQWSRSXODWLRQWKDQLVH[SHFWHGWR
EHSUHVFULEHGWKHPHGLFDWLRQSRVWDSSURYDO7KHQHHGIRUGDWDLQDPRUHUHSUHVHQWDWLYH
SRSXODWLRQLQFORVHWRDµUHDOZRUOG¶VHWWLQJLVLQFUHDVLQJO\EHLQJUHFRJQLVHGDVLPSRUWDQW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
17
WRFRPSOHPHQWSLYRWDOSKDVH,,,VDIHW\DQGHIILFDF\VWXGLHVLQRUGHUWRHVWDEOLVKWKH
EHQHILWVDQGWKHUHIRUHWKHYDOXHRIDPHGLFDWLRQLQWKHFRQWH[WRIFOLQLFDOSUDFWLFH,QGHHG
LQWKHFORVHWRµUHDOOLIH¶FRQGLWLRQVSK\VLFLDQVKDYHWKHDELOLW\WRFKRRVHWKHEHVW
WUHDWPHQWLQWKHLUYLHZIRUDQ\LQGLYLGXDOSDWLHQWDQGDGDSWWUHDWPHQWVWRVXEMHFWV¶
FKDUDFWHULVWLFVDQGUHVSRQVH7KXVGRXEOHEOLQGFRPSDULVRQRIRQFHGDLO\WRWZLFHGDLO\
PHGLFLQHVZKLOHLPSRUWDQWIRUDVVHVVLQJHIILFDF\UHPRYHVDSRWHQWLDOVRXUFHRI
GLIIHUHQFHLQHIIHFWLYHQHVVGHULYHGIURPSDWLHQWEHKDYLRXUDQGH[SHULHQFH0RUHRYHUD
KHDGWRKHDGVWXG\FRPSDULQJ5HOYDUPFJPFJ(OOLSWD))9,RQFHDGD\YV
6HUHWLGH9LDQL PFJPFJ'LVNXV)OXWLFDVRQHSURSLRQDWHVDOPHWHUROWZLFHDGD\
IDLOHGWRGHPRQVWUDWHVXSHULRULW\RQKRXUVZHLJKWHGPHDQ)(9DIWHUPRQWKVRI
WUHDWPHQW+RZHYHURIVXEMHFWVLQERWKDUPVZHUHXQFRQWUROOHG$&7VFRUHDW
UDQGRPLVDWLRQDIWHUZHHNVRI)OXWLFDVRQHSURSLRQDWHPFJWZLFHDGD\)RUWKLV
VXEJURXSRIVXEMHFWVDWWKHHQGRIWKHPRQWKWUHDWPHQWSHULRGRIVXEMHFWVZHUH
FRQWUROOHGLQWKH))9,DUPYVLQWKH6HUHWLGH9LDQL 'LVNXVDUP7KHVWXG\ZDVQRW
SRZHUHGRQWKLVFULWHULRQQRUGHVLJQHGWRLQFOXGHXQFRQWUROOHGVXEMHFWVRQO\$Q\ZD\
WKLVWUHQGMXVWLILHVH[SORULQJLIWKLVGLIIHUHQFHZRXOGGLVDSSHDURULQFUHDVHLQDFORVHWR
UHDOOLIHVHWWLQJ
6XEMHFWVUHFUXLWHGLQWRWKHVWXG\ZLOOEHWKRVHFXUUHQWO\WDNLQJDQ,&6DORQHZLWKRXWDQ\
RWKHUFRQWUROOHUWUHDWPHQWZLWKHYLGHQFHRIVXERSWLPDODVWKPDFRQWUROFRUUHVSRQGLQJWR
(XURSHDQ0DUNHWLQJ$XWKRULVDWLRQRI))9,7KHVHVXEMHFWVZLOOEHUDQGRPLVHGWR
UHFHLYH))9,YLD(OOLSWDLQKDOHURQFHGDLO\RUWRUHFHLYHXVXDO,&6/$%$IL[HG
FRPELQDWLRQLQ'3,IOXWLFDVRQHSURSLRQDWHVDOPHWHURO)36YLD'LVNXVLQKDOHUDQG
EXGHVRQLGHIRUPRWHURO%8')YLD7XUEXKDOHUWZLFHGDLO\IRUDVWKPDPDLQWHQDQFH
WKHUDS\DVSHUQRUPDOFOLQLFDOSUDFWLFH (OOLSWDLVDQHZSRZGHULQKDOHUGHVLJQHGWREH
HDV\WRXVH&XUUHQWSRZGHULQKDOHUVKDYHEHHQDVVRFLDWHGZLWKKDQGOLQJHUURUVVRPHRI
ZKLFKPD\LPSDFWWKHDELOLW\RIGUXJWRUHDFKWKHOXQJDQGKHQFHLPSDFWFOLQLFDOHIILFDF\
6XFKHUURUVGHHPHGDVFULWLFDOZLOOEHHYDOXDWHGLQWKLVVWXG\EHWZHHQGLIIHUHQWLQKDOHUV
DVZHOODVRYHUDOOLQKDOHUSUHIHUHQFHDQGVDWLVIDFWLRQ

%ULHI%DFNJURXQG
$VWKPDLVDFKURQLFGLVHDVHRIWKHOXQJVFKDUDFWHULVHGE\DLUZD\LQIODPPDWLRQ
EURQFKRFRQVWULFWLRQDQGLQFUHDVHGDLUZD\UHVSRQVLYHQHVV,QKDOHGFRUWLFRVWHURLGV,&6
DUHFRQVLGHUHGWKHPRVWHIIHFWLYHDQWLLQIODPPDWRU\WUHDWPHQWVIRUDOOVHYHULWLHVRI
SHUVLVWHQWDVWKPD>*,1$1,+%ULWLVK7KRUDFLF6RFLHW\@ 7KHEHQHILWV
RI,&6LQFOXGHFRQWURORIDVWKPDV\PSWRPVLPSURYHPHQWLQOXQJIXQFWLRQGHFUHDVHLQ
DLUZD\K\SHUUHVSRQVLYHQHVVDQGSRVVLEO\SUHYHQWLRQRIDLUZD\ZDOOUHPRGHOOLQJ
>3HGHUVHQ)DQWD@
)OXWLFDVRQHIXURDWHLVDQRYHOJOXFRFRUWLFRLGGHYHORSHGIRUXVHDVDRQFHGDLO\LQKDOHG
WUHDWPHQWIRUDVWKPD7KHGUXJFRQVLVWVRI))IRUPXODWHGLQODFWRVHIRURUDOLQKDODWLRQYLD
WKH'3,(OOLSWD3UHFOLQLFDOGDWDDQGHDUO\SKDVHFOLQLFDOVWXGLHVLQGLFDWHWKDW))KDVD
ORQJHUGXUDWLRQRIDFWLRQWKDQIOXWLFDVRQHSURSLRQDWH)3DQGLVWKHUHIRUHVXLWDEOHIRU
GHYHORSPHQWIRURQFHGDLO\DGPLQLVWUDWLRQ
9LODQWHUROLVDQRUDOO\LQKDOHGORQJDFWLQJDJRQLVWRIWKHEHWDDGUHQRFHSWRU/$%$DQG
KDVEHHQGHYHORSHGIRUXVHLQFRPELQDWLRQZLWK,&6DVDRQFHGDLO\PDLQWHQDQFH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
18
WUHDWPHQWRIDVWKPD7KHGUXJFRQVLVWVRIYLODQWHUROIRUPXODWHGLQODFWRVHDQGPDJQHVLXP
VWHDUDWHIRURUDOLQKDODWLRQYLD(OOLSWD
7KHFRPELQDWLRQRIWKHVHWZRDJHQWVKDVEHHQGHYHORSHGDVDRQFHGDLO\FRPELQDWLRQ
WKHUDS\IRUWKHORQJWHUPPDLQWHQDQFHWUHDWPHQWRIDVWKPDLQDGXOWVDQGFKLOGUHQ∀
\HDUVRIDJH7KHDYDLODELOLW\RIDRQFHGDLO\,&6FRPELQHGZLWKD/$%$ZRXOGEH
H[SHFWHGWRKHOSWRLPSURYHFRPSOLDQFHDQGWKHUHIRUHLPSURYHDVWKPDFRQWURO
,QIRUPDWLRQRQWKHSK\VLFDOFKHPLFDODQGSKDUPDFHXWLFDOSURSHUWLHVRIIOXWLFDVRQH
IXURDWHYLODQWHURODQGIOXWLFDVRQHIXURDWHYLODQWHUROPD\EHIRXQGLQ6P3&RU
,QYHVWLJDWRU%URFKXUH

2%-(&7,9(6$1'(1'32,176
7KLVRSHQODEHOUDQGRPLVHGFOLQLFDOVWXG\ZLOOHYDOXDWHWKHHIILFDF\DQGVDIHW\RI
IOXWLFDVRQHIXURDWH))YLODQWHURO9,,QKDODWLRQ3RZGHU))PFJ9,PFJRU))
PFJ9,PFJ FRPSDUHGZLWKH[LVWLQJIL[HGFRPELQDWLRQV,&6/$%$,QKDOHG
&RUWLFRVWHURLGV/RQJ$FWLQJ%HWD$JRQLVWVLQKDODWLRQSRZGHUVIOXWLFDVRQH
SURSLRQDWHVDOPHWHURO)36DQGEXGHVRQLGHIRUPRWHURO%8')IRUDVWKPD
PDLQWHQDQFHWKHUDS\LQD³FORVHWRUHDOOLIH´PDQQHULQSULPDU\ FDUH DQGLQUHVSLUDWRU\
VSHFLDOLVWFDUHUHVHDUFKVLWHV))9,ZLOOEHDGPLQLVWHUHGRQFHGDLO\4'YLD(OOLSWD DQG
)36RU%8')WZLFHGDLO\%,'YLD'LVNXVDQG7XUEXKDOHUUHVSHFWLYHO\
Objectives
Endpoints
Primary
!
7RFRPSDUHWKHHIILFDF\RI))9,
PFJPFJRU)) PFJPFJ
ZLWKXVXDOIL[HGFRPELQDWLRQV
,&6/$%$IRUDVWKPDPDLQWHQDQFH
WKHUDS\DW:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQWKH$VWKPD
&RQWURO7HVW$&7WRWDOVFRUHDW:HHN
9LVLW
Secondary
!
7RDVVHVVHIIHFWRI))9,RQDVWKPD
FRQWUROFRPSDUHGZLWKXVXDO,&6/$%$
IL[HGFRPELQDWLRQDW:HHN9LVLW
!
7RDVVHVV(//,37$LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXVDQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
!
&KDQJHIURP EDVHOLQHLQ$&7VFRUHDW
:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWV ZLWKFRUUHFWXVH
RIGHYLFHGHILQHGDVQRWPDNLQJDQ\
FULWLFDOHUURURUQRQFULWLFDOHUURU DW
:HHN9LVLWDQGDW:HHN9LVLW
LQGHSHQGHQWO\RIWKHXVHDW:HHN
9LVLW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
19
Objectives
Endpoints
Other
7RDVVHVVHIIHFWRI))9,RQSUHGRVHWURXJK
)(9FRPSDUHGZLWKXVXDO,&6/$%$IL[HG
FRPELQDWLRQDW:HHN9LVLW
7RDVVHVVWKHHIIHFWRI))9,RQUHVSRQVHWR
WUHDWPHQWDW:HHN9LVLWDQG:HHN
9LVLW
7RDVVHVVWKHFRPSOLDQFHZLWKVWXG\
PHGLFDWLRQDQGVHOIUHSRUWHGDGKHUHQFHWR
VWXG\PHGLFDWLRQDW:HHN9LVLWDQG
:HHN9LVLW
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQRYHUWKHVWXG\SHULRG
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIHDW:HHN9LVLW
&KDQJHIURPEDVHOLQHLQSUHGRVHWURXJK
)(9DW:HHN9LVLW
$&7VFRUHRUSRLQWLQFUHDVHIURP
EDVHOLQHLQ$&7DW:HHN9LVLWDQG
:HHN9LVLW1RWH$SRLQWLQFUHDVH
LQ$&7WRWDOVFRUHZDVVXJJHVWHGDVWKH
0LQLPDO&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]@
$&7VFRUHDW:HHN9LVLWDQG
:HHN9LVLW
&KDQJHIURPEDVHOLQHLQLQGLYLGXDOTXHVWLRQ
VFRUHVIRU$&7DW:HHNV
&RPSOLDQFH ZLWK VWXG\ PHGLFDWLRQ IURP
UDQGRPLVDWLRQ 'D\  WR :HHN  9LVLW
 IURP :HHN  9LVLW  WR :HHN 
9LVLWDQGIURPUDQGRPLVDWLRQ'D\WR
:HHN9LVLW
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ $GKHUHQFH 5HSRUW 6FDOH IRU
$VWKPD DW WKH UDQGRPLVDWLRQ 'D\
:HHN9LVLWDQG:HHN9LVLW
1XPEHURIVXEMHFWZLWKDWOHDVWVHYHUH
DVWKPDH[DFHUEDWLRQQXPEHURIVHYHUH
DVWKPDH[DFHUEDWLRQDQGDQQXDOVHYHUH
H[DFHUEDWLRQUDWHRYHUWKHVWXG\SHULRG
&KDQJH IURP EDVHOLQH LQ WRWDO VFRUH DQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUHDW:HHN
9LVLW
$Q LQFUHDVH IURP EDVHOLQH RI   LQ
$4/4VWRWDOVFRUHDW:HHN9LVLW
$Q LQFUHDVH IURP EDVHOLQH RI   LQ

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
20
Objectives
Endpoints
7RDVVHVV3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH
DVVHVVPHQWZLWKGLIIHUHQWLQKDOHUV DW:HHN
9LVLW
7RHYDOXDWHWKH6DIHW\RI))9,FRPSDUHG
ZLWKXVXDO,&6/$%$)36DQG%XG)
$4/4V HQYLURQPHQWDO VWLPXOL GRPDLQ
VFRUHDW:HHN9LVLW
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVHIURPEDVHOLQHRILQ$4/46
,QGLYLGXDOGRPDLQVFRUHVDW:HHN9LVLW

&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
+HDOWK
VWDWXV
XVLQJ
WKH
(XUR4RO
4XHVWLRQQDLUH (4' DW :HHN  9LVLW

6FRUH RI 3$6$3 4XHVWLRQQDLUH 3DWLHQW
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN 
9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
)UHTXHQF\ DQG W\SH RI VHULRXV DGYHUVH
HYHQWV
)UHTXHQF\DQGW\SHRIQRQVHULRXVDGYHUVH
GUXJUHDFWLRQVUHODWHGWRWUHDWPHQW
$VHYHUHDVWKPDH[DFHUEDWLRQZLOOEHGHILQHGDVGHWHULRUDWLRQRIDVWKPDUHTXLULQJWKH
XVHRIV\VWHPLFFRUWLFRVWHURLGV WDEOHWVVXVSHQVLRQRULQMHFWLRQIRUDWOHDVWGD\VRUDQ
LQSDWLHQW KRVSLWDOLVDWLRQ RU HPHUJHQF\ GHSDUWPHQW YLVLW GXH WR DVWKPD WKDW UHTXLUHG
V\VWHPLFFRUWLFRVWHURLGV 
1RWHVGHILQLQJHQGSRLQWV
 &RQWDFWV ZLWK D GRFWRU RU KRVSLWDOLVDWLRQ DUH GHILQHG DV H[DFHUEDWLRQUHODWHG
FRQWDFWV LI WKHVH FRQWDFWV ZHUH D GLUHFW UHVXOW RI DQ DFXWH ZRUVHQLQJ RI DVWKPD
V\PSWRPV
 $SUHVFULSWLRQRIV\VWHPLFFRUWLFRVWHURLGLVGHILQHGDVH[DFHUEDWLRQUHODWHGLIWKH
UHDVRQWKHGUXJZDVJLYHQLQZKROHRULQSDUWZDVWRWUHDWDQDFXWHZRUVHQLQJRI
DVWKPDV\PSWRPV
 ([DFHUEDWLRQUHODWHGKRVSLWDOLVDWLRQLQFOXGHVKRVSLWDOLVDWLRQWKDWLVSURORQJHGDVD
UHVXOWRIDQDVWKPDH[DFHUEDWLRQ

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
21

678'<'(6,*1

2YHUDOO'HVLJQ
7KLVLVD3KDVH,,,EPXOWLFHQWHUUDQGRPLVHGRSHQODEHOSDUDOOHOJURXSVWXG\SHUIRUPHG
LQVXEMHFWVLQSULPDU\FDUHDQGLQUHVSLUDWRU\FDUHVSHFLDOLVWUHVHDUFKVLWHV ZKRKDYHD
GLDJQRVLVRIDVWKPDDQGDUHJXODUWUHDWPHQWIRU SHUVLVWHQWDVWKPD6XEMHFWVZLWK
XQVDWLVIDFWRULO\FRQWUROOHGDVWKPDGHILQHGDVDQ$&7DQGLQWHQGHGWREHWUHDWHGE\
XVXDO,&6/$%$PDLQWHQDQFHWKHUDS\WRVHHNDEHWWHUFRQWURORIWKHLUDVWKPDZLOOEH
UDQGRPLVHGWRUHFHLYHHLWKHU))9,))9,PFJPFJRU))9,PFJPFJRQFH
GDLO\RUDQRWKHUXVXDO,&6/$%$FRPELQDWLRQWKHUDS\LQLQKDODWLRQSRZGHUWZLFHGDLO\
)36RU%8')GHFLGHGE\WKHLQYHVWLJDWRU7KHVHPHGLFDWLRQVDUHUHFRUGHGLQWKHH
&5)
,QYHVWLJDWRUVZLOOEHDOORZHGGXULQJWKHWUHDWPHQWSHULRGWRDGDSWSUHVFULSWLRQWRGLIIHUHQW
GRVHVLIQHFHVVDU\DVZHOODVWRDGDSWGRVHVRIWKHFRPSDUDWLYHWUHDWPHQWDFFRUGLQJWR
SURGXFWVODEHO$WDEOH7DEOH6HFWLRQRIWKHLQGLFDWLYHGRVDJHHTXLYDOHQFH
EHWZHHQ,&6DQGWKHRWKHUFRPELQDWLRQWKHUDSLHVZLOOEHSURYLGHGWRWKHLQYHVWLJDWRUV
1RWH7RPDLQWDLQFRQVLVWHQF\DFURVV FRXQWULHVWKHFKRLFHRIXVXDOLQKDOHGGU\SRZGHU
,&6/$%$IL[HGFRPELQDWLRQZLOOEHOLPLWHGWR6HUHWLGH9LDQL'LVNXV)36
PFJPFJRUPFJPFJRU6\PELFRUW7XUEXKDOHU %8')PFJPFJRU
PFJPFJ6RPH FRXQWULHV KDYHRWKHU,&6/$%$IL[HG FRPELQDWLRQVDQGRWKHU
JHQHULFYHUVLRQVRI)36DQG%8') DYDLODEOHIRUWKHWUHDWPHQWRISDWLHQWVZLWKDVWKPD
EXWWKHVHZLOOQRWEHSHUPLWWHGLQWKLVVWXG\$GGLWLRQDOO\VRPH FRXQWULHVKDYH RSWLRQV
IRUDORZHUGRVHRI9LDQL'LVNXV)36PFJPFJDQG6\PELFRUW7XUERKDOHU
%8')PFJPFJEXWWKHVHZLOOQRWEHSHUPLWWHGLQWKLVVWXG\
)RU6WXG\6FKHPDWLFVHH$SSHQGL[
,QYHVWLJDWRUV
*HQHUDO3UDFWLWLRQHUVDQGSXOPRQRORJLVWVDSSURYHGE\DQ(WKLFV&RPPLWHH ZLOOEH
DSSURDFKHGWRSDUWLFLSDWHLQWKHVWXG\
6FUHHQLQJUDQGRPLVDWLRQDQGIROORZXS
$WWKH6FUHHQLQJ9LVLWHOLJLEOHVXEMHFWVZLOOEHFRQVHQWHGWRSDUWLFLSDWHWRWKHWULDODQG
WKHQHFHVVDU\H[DPLQDWLRQV ZLOOEHSHUIRUPHG7KHVXEMHFWVZLOOEHDVNHGWRSURYLGH
UHVSRQVHVWRWKH$&7$VFUHHQLQJORJZLOOEHSHUIRUPHGDWWKLVYLVLW
$WDIXUWKHUYLVLWLH9'D\RFFXUULQJZLWKLQZHHNDIWHUWKHVFUHHQLQJYLVLW9
VXEMHFWVZKRPHHWDOORIWKH,QFOXVLRQ&ULWHULDQRQHRIWKH([FOXVLRQ&ULWHULDDQGZKR
DFFHSWWRJLYHWKHLUFRQVHQWZLOOEHUDQGRPLVHGLQWKHVWXG\5DQGRPLVDWLRQDWWKLVYLVLW
ZLOOEHRQDEDVLVWRWKH))9,IL[HGGRVHFRPELQDWLRQGHOLYHUHGE\(OOLSWD RUWRWKH
LQLWLDWLRQRIWKHXVXDO,&6/$%$'3,IRUDVWKPDPDLQWHQDQFHWKHUDS\FKRVHQE\WKH
LQYHVWLJDWRU9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLVXVXDO
DVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG9LVLWDUHFRPELQHGWKHQWKLV
YLVLWZLOOEH'D\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
22
3DWLHQWVZKRIDLOVFUHHQLQJPD\EHUHVFUHHQHGRQO\XSRQ DSSURYDOE\WKHPHGLFDO
PRQLWRU
$W9LVLW5DQGRPLVDWLRQYLVLW'D\EDVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGE\WKH
,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.$WOHDVWWKUHHDVVHVVPHQWVVKRXOGEH
SHUIRUPHGZLWKUHJLVWUDWLRQRIWKHEHVWYDOXH$WOHDVWWZRRIWKHVSLURPHWU\HIIRUWV
VKRXOGEHDFFHSWDEOHDQGUHSHDWDEOH2QWKHPRUQLQJRI9LVLWVXEMHFWVZLOOQRWWDNH
WKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHGKRXUV
EHIRUHEDVHOLQHVSLURPHWU\
,QDGGLWLRQDW 9LVLWVXEMHFWVZLOOEHDVNHGWRUHDGWKHZULWWHQ(OOLSWDSDFNDJHLQVHUWLI
UDQGRPLVHGLQWRWKH))9,DUPRU'LVNXVRU7XUEXKDOHUSDFNDJHLQVHUWLIUDQGRPLVHGLQ
WKHXVXDO,&6/$%$WKHUDS\DUP DQGZLOOEHLQVWUXFWHGE\WKHLQYHVWLJDWRURQWKHSURSHU
XVHRILQKDOHUV7KHQWKHVXEMHFWZLOOVHOIDGPLQLVWHUWKHLUILUVWGRVHRIVWXG\GUXJXQGHU
VXSHUYLVLRQRIWKHLQYHVWLJDWRU$Q\FULWLFDOHUURUGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\
WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJLQKDOHGRUQRQFULWLFDOHUURUZLOOEH
UHJLVWHUHGE\WKHWUDLQHG+&3$IWHUFRPSOHWLQJWKHSURFHGXUHVXEMHFWVZLOOEHLQVWUXFWHG
LQWKHFRUUHFWXVHRIWKHGHYLFHE\WKH LQYHVWLJDWRURUVXLWDEO\TXDOLILHGGHVLJQHH LI
QHHGHG7KHUHDIWHUHDFKVXEMHFWUDQGRPLVHGLQWRWKH))9,DUP ZLOOEHLQVWUXFWHGWRVHOI
DGPLQLVWHURQHLQKDODWLRQZLWK(OOLSWDLQKDOHUHDFKGD\DWWKHVDPHWLPHRIWKHGD\DWD
WLPHWKDWLVFRQYHQLHQWIRUWKHVXEMHFW6XEMHFWUDQGRPLVHGLQWRXVXDO,&6/$%$WKHUDS\
DUPZLOOEHLQVWUXFWHGWRVHOIDGPLQLVWHUWKHLQKDODWLRQZLWK'LVNXVRU7XUEXKDOHULQKDOHU
WZLFHDGD\
6XEMHFWVZLOOEHUHFRPPHQGHGWRXVHVDOEXWDPRODVQHHGHGWKURXJKRXWWKHVWXG\IRU
UHOLHIRIWKHLUDVWKPDV\PSWRPV$W9LVLWUDQGRPLVDWLRQ'D\VXEMHFWZLOOEHDVNHG
WRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
$W:HHN 9LVLWDQGDW:HHN9LVLWVXEMHFWVZLOOEHWHOHSKRQHGE\WKH
,QYHVWLJDWRUWRHQTXLUHDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVHHYHQWV
RQO\WKHVHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQVZLOOEHUHFRUGHGLQ
H&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRWWRVWXG\
WUHDWPHQW$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWR SURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJFULWLFDODQG
QRQFULWLFDOHUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRIVWXG\
GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQ
FDVHRIPXOWLSOHHUURUVGHWHFWLRQ3UHGRVHWURXJK)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJWKHVSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPRO
ZLOOEHVWRSSHGKRXUVEHIRUHWKHVSLURPHWU\$WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOGEH
SHUIRUPHGZLWKUHJLVWUDWLRQRIWKHEHVWYDOXH $WWKLVYLVLWVXEMHFWVZLOODOVREH
LQWHUYLHZHGE\WKH,QYHVWLJDWRUDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVH
HYHQWVRQO\WKHVHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQVZLOOEH
UHFRUGHGLQH&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
23
WRVWXG\WUHDWPHQW)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREHUHPLQGHGDERXW
WKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KHILQDO9LVLWZLOORFFXU DW:HHN7KH$&7$4/46(4'DQG0$56$
TXHVWLRQQDLUHVZLOOEHFRQGXFWHGDWWKLVYLVLWDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\
UHFRUGLQJFULWLFDODQGQRQFULWLFDOHUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQ
RIRQHGRVHRIVWXG\GUXJE\VXEMHFWHUURUVDVVHVVPHQWE\WKH,QYHVWLJDWRU
GHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ6XEMHFWVZLOO
EHLQWHUYLHZHGDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRU
QRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUW
WRVFKHGXOH9LVLWDWWKHVDPHWLPHRIWKHGD\DV9LVLW
$OWKRXJKDWOHDVWIRUPDOVFKHGXOHGYLVLWVDQGSKRQHFDOOVDUHSODQQHGIRUWKLVVWXG\
VXEMHFWVVKRXOGFRQWLQXHWRYLVLWWKHLUSK\VLFLDQIRUDQ\URXWLQHVWDQGDUGRIFDUH YLVLWVDV
SHUQRUPDOFOLQLFDOSUDFWLFHDVSHUWKH7LPHDQG(YHQWV7DEOH6HFWLRQ$Q(DUO\
:LWKGUDZDO9LVLW VKRXOGEHSHUIRUPHGLQFDVHRIHDUO\ZLWKGUDZDORIWKHVXEMHFWIURP
WKHVWXG\DVSHUWKH7LPHDQG(YHQWV7DEOH6HFWLRQ DQG 6HFWLRQ 6XEMHFW
:LWKGUDZDOE\,QYHVWLJDWRURU6HOIZLWKGUDZDO
3URWRFROZDLYHUVRUH[HPSWLRQVDUHQRWDOORZHGZLWKWKHH[FHSWLRQRILPPHGLDWHVDIHW\
FRQFHUQV7KHUHIRUHDGKHUHQFHWRWKHVWXG\GHVLJQUHTXLUHPHQWVLQFOXGLQJWKRVH
VSHFLILHGLQWKH7LPHDQG(YHQWV7DEOHDUHHVVHQWLDODQGUHTXLUHGIRUVWXG\FRQGXFW
6XSSOHPHQWDU\VWXG\FRQGXFWLQIRUPDWLRQQRWPDQGDWHGWREHSUHVHQWLQWKLVSURWRFROLV
SURYLGHGLQWKHDFFRPSDQ\LQJ6WXG\5HIHUHQFH0DQXDO6507KH650ZLOOSURYLGH
WKHVLWHSHUVRQQHOZLWKDGPLQLVWUDWLYHDQGGHWDLOHGWHFKQLFDOLQIRUPDWLRQWKDWGRHVQRW
LPSDFWVXEMHFWVDIHW\
2XWFRPHGHVFULSWLRQ
2QHRIWKHPDLQFKDOOHQJHVRIWKLVVWXG\SHUIRUPHGLQVRFDOOHGµFORVHWRUHDOOLIHVHWWLQJ¶
LVWRREWDLQGDWDRQVXEMHFWVZLWKPLQLPDOLQWHUIHUHQFHZLWKWKHDFWXDOSUDFWLFHRI
PHGLFLQH7KXVGXULQJWKHPRQWKVWUHDWPHQWSHULRGRIWKHVWXG\DOOLQWHUYHQWLRQVZLOO
EHUHFRUGHGDVSHUQRUPDO7KH\ZLOOEHFDSWXUHGE\VHYHUDOPHDQV

,QYHVWLJDWRUVSDUWLFLSDWLQJLQWKHVWXG\ZLOOEHDVNHGWRILOOLQDQHOHFWURQLF&5)
H&5)IRFXVHGRQFOLQLFDOGDWDDWVFUHHQLQJYLVLW9LVLWDWUDQGRPLVDWLRQ
9LVLWDW:HHN9LVLWDWWKHHQGRIWKHVWXG\DW:HHN9LVLWDQGDW
WZRSKRQHFDOOVDW:HHN9LVLWDQGDW:HHN9LVLW

$W:HHN DQGDW:HHNVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXWZKHWKHU
WKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVHHYHQWVDQGWKHQWKH,QYHVWLJDWRUFDOOLQJ
WKHSDWLHQWPXVWGHWHUPLQHZKHWKHUWKHHYHQWLVUHODWHGWRVWXG\PHGLFDWLRQHLWKHU
DUPDQGZKHWKHUWKHHYHQWLVVHULRXV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVR
EHDVNHGE\WKH,QYHVWLJDWRUWRFRPSOHWHWKH$&7TXHVWLRQQDLUHDQGWRVHQGLW
EDFNWRWKH,QYHVWLJDWRU

:KHQQHFHVVDU\ DQGSRVVLEOHLQIRUPDWLRQZLOOEHREWDLQHGIURPRWKHUPHGLFDO
VRXUFHVURXWLQHVWDQGDUG RIFDUHYLVLWV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
24
7KHYDULDEOHVRILQWHUHVWZLOOEHGRFXPHQWHGE\DFRPELQDWLRQRILQIRUPDWLRQFROOHFWHG
IURPDOOWKHVHVRXUFHV
&ROOHFWHGGDWD
(OLJLEOHVXEMHFWVZLOOFRPSOHWHWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
DW5DQGRPLVDWLRQ9LVLW9LVLW'D\DQGDW9LVLW:HHNRUDWWKH(DUO\
:LWKGUDZDOYLVLW$&7TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRE\WKHVXEMHFWDW6FUHHQLQJ
YLVLW9LVLW:HHNSKRQHFDOORU9LVLWDW:HHN9LVLWDQG:HHNSKRQH
FDOORU9LVLW0$56$TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRDW:HHN9LVLW
,QKDOHUXVHDVVHVVPHQWZLOOEHSHUIRUPHGDW5DQGRPLVDWLRQ9LVLW9LVLW'D\DW
:HHN9LVLWDQGDW:HHN9LVLW(DUO\:LWKGUDZDOYLVLWE\UHFRUGLQJWKH
FULWLFDODQGQRQFULWLFDOHUURUV3DWLHQW¶VVDWLVIDFWLRQDQGSUHIHUHQFH3$6$34ZLOOEH
HYDOXDWHGDW:HHN9LVLW
%DVHOLQHVSLURPHWU\ZLOOEHSHUIRUPHGDW5DQGRPLVDWLRQ9LVLW9LVLW'D\DQGDW
:HHN9LVLWE\WKH,QYHVWLJDWRUXVLQJWKHVSLURPHWHUSURYLGHGE\*6. LQRUGHUWR
DVVHVVSUHGRVHWURXJK)(9DW:HHN9LVLW
)RUWKH6WXG\6FKHPDWLFVHH$SSHQGL[ DQG6HFWLRQ IRUWKHSURSRVHGWLPHDQG
HYHQWVWDEOH

7UHDWPHQWDUPVDQGGXUDWLRQ
5DQGRPLVDWLRQZLOOEHRQDEDVLV ZLWKWZRWUHDWPHQWDUPVRQH))9,DUP))9,
PFJPFJRU))9,PFJPFJRQFHGDLO\DQGRQHDUP,&6/$%$FRPELQDWLRQ
WKHUDS\LQLQKDODWLRQSRZGHUWZLFHGDLO\)36PFJPFJRUPFJPFJRU
%8')PFJPFJRUPFJPFJDVGHFLGHGE\WKHLQYHVWLJDWRU 7KHWRWDO
GXUDWLRQRIVXEMHFWSDUWLFLSDWLRQZLOOEHDSSUR[LPDWHO\PRQWKVZHHNV$VPXFKDV
SRVVLEOHHQUROPHQWRIVXEMHFWVVKRXOGEHSHUIRUPHGDWDFRQVWDQWDFFUXDOUDWHWKURXJKRXW
DIXOO\HDULQRUGHUWRPLQLPL]HDVHDVRQDOLW\ELDV

7\SHDQG1XPEHURI6XEMHFWV
6XEMHFWVZLWKGRFXPHQWHGSK\VLFLDQ¶VGLDJQRVLVRIDVWKPD\HDUXQVDWLVIDFWRULO\
FRQWUROOHGDVWKPD$&7WUHDWHGE\,&6DORQHDQGLQWHQGHGWREHWUHDWHGE\
,&6/$%$PDLQWHQDQFHWKHUDS\
)UDQFH2QO\$VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\RQO\LIHLWKHUDIILOLDWHG
WRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\ VWXG\FHQWHUVZLOOEHUHTXLUHGWRKDYHDWRWDO
QXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDVFUHHQIDLOXUHUDWHDSSUR[LPDWHO\VXEMHFWVZLOOKDYHWREHVFUHHQHG
LQWKHVWXG\
6XEMHFWVZLWKGUDZQIURPWKHVWXG\ZLOOQRWEHUHSODFHG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
25

'HVLJQ-XVWLILFDWLRQ
$QRSHQODEHOGHVLJQLVDSSURSULDWHIRUVXFKDVWXG\EHFDXVHLWLVDFRPSDULVRQ RI
EHQHILWVDQGULVNVRI))9,YHUVXVXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\LQFORVH
WRUHDOOLIHVHWWLQJ
3UHYLRXVVWXGLHVKDYHGHPRQVWUDWHGWKDWLPSURYHPHQWVLQ$&7VFRUHFDQEHVHHQLQ
SHULRGVRIPRQWKVPDNLQJWKLVVXLWDEOHWLPHIUDPHWRDVVHVV $&7FKDQJHV
7KHWUHDWPHQWGXUDWLRQRIPRQWKVZHHNVLQWKLVVWXG\LVFRQVLGHUHGVXIILFLHQWWR
GHPRQVWUDWHHIILFDF\LQWKHSURSRVHGVWXG\SRSXODWLRQ
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQHLQWKH$&7WRWDOVFRUH
DVVHVVHGDW:HHN9LVLW7KHDLPZLOOEHWRSURYHQRQLQIHULRULW\RI))9,WRDQ\
RWKHU,&6/$%$FRPSDUDWRU7KHK\SRWKHVLVRIQRQLQIHULRULW\ZLOOEHILUVWWHVWHGDW
:HHN,IDQGRQO\LIQRQLQIHULRULW\LVVLJQLILFDQWO\DFKLHYHGDW:HHNQRQ
LQIHULRULW\ZLOOWKHQEHWHVWHGDW:HHN,IDQGRQO\LIQRQLQIHULRULW\LVDFKLHYHGDWD
YLVLWWKHQVXSHULRULW\RI))9,WRDQ\RWKHUFRPSDUDWRUZLOOEHWHVWHGDWWKLVYLVLW:HHN
RU:HHN

'RVH-XVWLILFDWLRQ
7ZRVWUHQJWKVRI))9,KDYHEHHQDSSURYHGPFJPFJGHOLYHUHGGRVHRI
PFJPFJIRUPRGHUDWHSHUVLVWHQWDVWKPD DQGPFJPFJ GHOLYHUHGGRVHRI
PFJPFJIRUVHYHUHSHUVLVWHQWDVWKPD7KHGRVHRIPFJPFJLVSUHIHUUHGLQ
WKLVVWXG\DVWKLVGRVHVWUHQJWKLVOLNHO\WRPHHWWKHQHHGVRIPRVWVXEMHFWV+RZHYHU
LQYHVWLJDWRUVZLOOEHDOORZHGWRFKDQJHWKHSUHVFULSWLRQWRKLJKHUGRVHDFFRUGLQJWR
VXEMHFW¶VUHVSRQVHZLWKRXWH[FHHGLQJWKHPD[LPXPDOORZHGGRVH

%HQHILW5LVN$VVHVVPHQW
6XPPDULHVRIILQGLQJVIURPERWKFOLQLFDODQGQRQFOLQLFDOVWXGLHVFRQGXFWHGZLWK))9,
FDQEHIRXQGLQWKH,QYHVWLJDWRU¶V%URFKXUH,%RU6XPPDU\RI3URGXFW&KDUDFWHULVWLFV
6P3&7KHIROORZLQJVHFWLRQRXWOLQHVWKHULVNDVVHVVPHQWDQGPLWLJDWLRQVWUDWHJ\IRU
WKLVSURWRFRO

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
26

5LVN$VVHVVPHQW
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
6HULRXV&DUGLRYDVFXODU(YHQWV
7KLVLVDSRWHQWLDOFODVVHIIHFWRI/$%$V,Q
FOLQLFDOVWXGLHVSHUFHQWDJHVRIVXEMHFWVZLWK
IDWDO HYHQWVWKDWZHUHFDUGLRYDVFXODULQ
QDWXUHZHUHVLPLODUDFURVVDOOWUHDWPHQW
JURXSVWR
6XEMHFWVZLWKKLVWRULFDORUFXUUHQWHYLGHQFH
RIXQFRQWUROOHGRUFOLQLFDOO\VLJQLILFDQW
GLVHDVHDUHH[FOXGHGIURPWKHVWXG\
&DUGLRYDVFXODUPHGLFDOKLVWRU\&9ULVN
IDFWRUVDQGH[DFHUEDWLRQKLVWRU\ZLOOEH
DVVHVVHGDVGHVFULEHGLQWKHWLPHDQGHYHQWV
WDEOH
$VWKPDUHODWHGLQWXEDWLRQVDQGGHDWKV
7KLVLVDSRWHQWLDOFODVVHIIHFWRI/$%$V,W
ZDVQRWREVHUYHGLQSUHFOLQLFDOVWXGLHVZLWK
))9,'XULQJWKH))9,VWXGLHVIRUWKH
DVWKPDFRPSRVLWHHQGSRLQWDVWKPD
H[DFHUEDWLRQVOHDGLQJWRKRVSLWDOL]DWLRQ
LQWXEDWLRQDQGRUGHDWKWKHUHZDVQR
VLJQLILFDQWGLIIHUHQFH
EHWZHHQWKH))9,JURXSDQGWKH,&6JURXS
RUQRQ/$%$JURXSGHPRQVWUDWLQJQR
LQFUHDVHGULVNZKHQDGGLQJD/$%$WRDQ
,&6
6XEMHFWVZLWKDKLVWRU\RIOLIHWKUHDWHQLQJ
DVWKPDDUHH[FOXGHGIURPWKLVVWXG\
6XEMHFWVDUHH[FOXGHGIURPWKLVVWXG\LIWKH\
KDYHDVHYHUHDQGXQVWDEOHDVWKPDZLWK
$&7 VFRUHKLVWRU\RIUHSHDWHGVHYHUH
H[DFHUEDWLRQV\HDUDQGRUH[DFHUEDWLRQ
LQWKHSUHYLRXVZHHNV
6XEMHFWVDUHH[FOXGHGIURPWKLVVWXG\LIWKH\
DUHXVLQJ/$%$ZLWKRXWDQ,&6DVDVWKPD
PDLQWHQDQFHWKHUDS\



2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
27
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
+\SHUVHQVLWLYLW\
7KHUHSRUWHGK\SHUVHQVLWLYLW\HYHQWVLQ
FOLQLFDOWULDOVZHUHQRWJHQHUDOO\VHULRXV
GLGQRWOHDGWRGLVFRQWLQXDWLRQLQWKH
VWXGLHVDQGZHUHXVXDOO\FRQIRXQGHGE\
HLWKHUWKHVXEMHFW¶VPHGLFDOFRQGLWLRQVXFK
DV&23'RURWKHUIDFWRUVDWWKHWLPHRIWKH
HYHQW
,QVSRQWDQHRXVGDWDV\PSWRPVRI
K\SHUVHQVLWLYLW\UDQJHGIURPPLOGUDVKDQG
SUXULWLV WRVHYHUHJHQHUDOLVHGUDVKDQG
HU\WKHPDDQGVHYHUHFDVHVLQYROYLQJ
DQJLRGHPDRIWKHIDFHODU\Q[DQGSKDU\Q[
7KHVHHYHQWVZHUHUDUH
6XEMHFWV ZLWKDKLVWRU\ RIDGYHUVHUHDFWLRQ
LQFOXGLQJ
LPPHGLDWH
RU
GHOD\HG
K\SHUVHQVLWLYLW\ WR DQ\ LQWUDQDVDO LQKDOHG
RU V\VWHPLF FRUWLFRVWHURLG DQG /$%$
WKHUDS\DQGWRFRPSRQHQWVRIWKHLQKDODWLRQ
SRZGHU HJ ODFWRVH PDJQHVLXP VWHDUDWH
ZLOOEHH[FOXGHG,QDGGLWLRQVXEMHFWVZLWK
DKLVWRU\RIVHYHUHPLONSURWHLQDOOHUJ\WKDW
LQ
WKH
RSLQLRQ
RI
WKH
,QYHVWLJDWRU
FRQWUDLQGLFDWHV WKH VXEMHFW¶V SDUWLFLSDWLRQ
ZLOODOVREHH[FOXGHG
6\VWHPLFHIIHFWVRIFRUWLFRVWHURLGVDGUHQDO
VXSSUHVVLRQH\HGLVRUGHUVGHFUHDVHGERQH
GHQVLW\DQGDVVRFLDWHGIUDFWXUHV
$GUHQDOVXSSUHVVLRQLVDNQRZQFODVVHIIHFW
RIFRUWLFRVWHURLGV3UHFOLQLFDOVWXGLHV
VKRZHGWKDW))HIIHFWVDUHFRPSDUDEOHZLWK
RWKHUFRUWLFRVWHURLGV1RVWXGLHVKDYH
VKRZQDFOLQLFDOO\UHOHYDQWHIIHFWRI))9,
RQWKHK\SRWKDODPLFSLWXLWDU\D[LV+3$
7KLVLQFOXGHVDIRUPDO+3$VWXG\
+=$XVLQJKRXUVHUXPFRUWLVRO
PHDVXUHPHQWVDQGPXOWLSOHVWXGLHVZLWK
&23'DQGDVWKPDVXEMHFWVZKLFK
PRQLWRUHGXULQDU\FRUWLVRO'XULQJFOLQLFDO
7KHPLWLJDWLRQLQWKLVVWXG\IRUDOOV\VWHPLF
HIIHFWV RI FRUWLFRVWHURLGV LV WKDW FKURQLF
XVHUV
RI
V\VWHPLF
FRUWLFRVWHURLGV
DUH
H[FOXGHGIURPWKLVVWXG\DVXEMHFWZKRLQ
WKHRSLQLRQRIWKH,QYHVWLJDWRULVFRQVLGHUHG
WR
EH
D
FKURQLF
XVHU
RI
V\VWHPLF
FRUWLFRVWHURLGV IRU UHVSLUDWRU\ RU RWKHU
LQGLFDWLRQV LI XQVXUH GLVFXVV ZLWK WKH
PHGLFDOPRQLWRUSULRUWRVFUHHQLQJZLOOEH
H[FOXGHG



2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
28
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
GHYHORSPHQWQRHYHQWVRI$GUHQDO
6XSSUHVVLRQZHUHUHSRUWHG
(\HGLVRUGHUVDUHDNQRZQFODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDOVWXGLHVVKRZHG
))DWKLJKGRVHFRPSDUDEOHWRRWKHUKLJK
GRVHFRUWLFRVWHURLGV,QVWXG\+=$
))9,))DQG)3LQVXEMHFWVZLWKDVWKPD
IRUPDORSKWKDOPLFDVVHVVPHQWVZHUH
FRQGXFWHGLQFOXGLQJ/2&6,,,HYDOXDWLRQV
IRURFXODURSDFLWLHVWKURXJKRXWWKHVWXG\
7KLVVWXG\VKRZHGQRDSSDUHQWHIIHFWVRQ
OHQVRSDFLILFDWLRQFRPSDUHGWREDVHOLQH
'XULQJVWXGLHVLQERWKVXEMHFWVZLWKDVWKPD
DQG&23'QRDVVRFLDWHGDIIHFWRQRFXODU
GLVRUGHUVZDVREVHUYHG
'HFUHDVHGERQHGHQVLW\LVDNQRZQFODVV
HIIHFWRIFRUWLFRVWHURLGV 3UHFOLQLFDOGDWD
VKRZHGWKDWKLJKGRVHFRUWLFRVWHURLGHIIHFWV
RI))ZHUHFRPSDUDEOHWRRWKHU
FRUWLFRVWHURLGV3DWLHQWVZLWK$VWKPD,QDQ
LQWHJUDWHGDQDO\VLVRIVWXGLHVLQDVWKPD
SDWLHQWVWKHLQFLGHQFHRIIUDFWXUHV
ZLWK))9,ZDV DQGXVXDOO\
DVVRFLDWHGZLWKWUDXPD



2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
29
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Procedures
6SLURPHWU\SURFHGXUHV
6KRUWQHVVRIEUHDWKFRXJKLQJOLJKW
KHDGHGQHVVRUIDLQWLQJDQGRUFKHVW
WLJKWQHVV
,IDQ\RIWKHVHV\PSWRPVVKRXOGKDSSHQWR
WKHVXEMHFWVSLURPHWU\ZLOOEHVWRSSHGDQG
KHVKHZLOOUHFHLYHPHGLFDOWUHDWPHQW
Other 
6XPPDULHVRIILQGLQJVIURPERWKFOLQLFDODQGQRQFOLQLFDOVWXGLHVFRQGXFWHGZLWKFRPSDUDWRUV6HUHWLGH9LDQL 'LVNXVDQG6\PELFRUW
7XUEXKDOHUFDQEHIRXQGLQWKH6XPPDU\RI3URGXFW&KDUDFWHULVWLFV6P3&



2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
30

%HQHILW$VVHVVPHQW
&RPELQHGWUHDWPHQWZLWK,&6DQG/$%$KDVEHHQVKRZQWREHPRUHHIIHFWLYHWKDQWKH
LQGLYLGXDOFRPSRQHQWVLQDVWKPDOHDGLQJWRWKHGHYHORSPHQWRIIL[HGGRVHFRPELQDWLRQ
LQKDOHUV7KHXVHRI,&6/$%$FRPELQDWLRQVLVQRZZHOOHVWDEOLVKHGLQLQWHUQDWLRQDO
WUHDWPHQWJXLGHOLQHVIRUPRGHUDWHWRVHYHUHSHUVLVWHQWDVWKPDSDWLHQWVIRUZKRP
WUHDWPHQWZLWK,&6DORQHLVQRWVXIILFLHQW
%RWKIOXWLFDVRQHSURSLRQDWHVDOPHWHURODQGEXGHVRQLGHIRUPRWHUROIXPDUDWHDUH
FRPPHUFLDOO\DYDLODEOHSURGXFWVIRUWKHWUHDWPHQWRISHUVLVWHQWDVWKPDDQGKDYH
UHFRJQL]HGVDIHW\SURILOHV%RWKRIWKHVHSURGXFWVDUHDGPLQLVWHUHGWZLFHGDLO\

2YHUDOO%HQHILW5LVN&RQFOXVLRQ
7KHLQYHVWLJDWLRQDOSURGXFW,3))9,KDVDQDFFHSWDEOHVDIHW\SURILOHIRU FOLQLFDOXVH
DQGWKHUHDUHQRVLJQLILFDQWDVVRFLDWHGULVNV7KLVFRQFOXVLRQLVVXSSRUWHGWKHUHVXOWVRI
SUHYLRXVO\SHUIRUPHGFOLQLFDOVWXGLHVZLWKWKHSURGXFWVLQKHDOWK\ YROXQWHHUVDQGVXEMHFWV
ZLWK$VWKPDDQG&23'*OD[R6PLWK.OLQH'RFXPHQW1XPEHU 50
$GYHUVHHIIHFWVWKDWFRXOGEHDVVRFLDWHGZLWKWKHXVHRI))9,ZLOO EHFORVHO\PRQLWRUHG
$VDIHW\FULWHULRQRXWOLQLQJGHWDLOVIRUVXEMHFWZLWKGUDZDOLV LQFOXGHGLQWKHSURWRFRO
6HFWLRQ :LWKGUDZDO&ULWHULD$WKRURXJKVXPPDU\DQG HYDOXDWLRQRIWKHDYDLODEOH
SUHFOLQLFDOGDWDFDQEHIRXQGLQWKH,%>*OD[R6PLWK.OLQH 'RFXPHQW1XPEHU
50@5RXWLQHVDIHW\DQDO\VLVRIWKLVVWXG\ZLOOEH FRQGXFWHGE\WKH
FRPSDQ\ 7DNLQJLQWRDFFRXQWWKHPHDVXUHVWDNHQWRPLQLPL]HULVNWRVXEMHFWV
SDUWLFLSDWLQJLQWKLV VWXG\WKHSRWHQWLDOULVNVLGHQWLILHGLQDVVRFLDWLRQZLWK))9,DUH
MXVWLILHGE\WKHDQWLFLSDWHGEHQHILWVWKDWPD\EHDIIRUGHGWRSDWLHQWVZLWKDVWKPD

6(/(&7,212)678'<3238/$7,21$1'
:,7+'5$:$/&5,7(5,$
6SHFLILFLQIRUPDWLRQUHJDUGLQJZDUQLQJVSUHFDXWLRQVFRQWUDLQGLFDWLRQVDGYHUVHHYHQWV
DQGRWKHUSHUWLQHQWLQIRUPDWLRQRQWKH*6.LQYHVWLJDWLRQDOSURGXFWRURWKHUVWXG\
WUHDWPHQWWKDWPD\LPSDFWVXEMHFWHOLJLELOLW\LVSURYLGHGLQWKH,%,%VXSSOHPHQWVRU
WKH6P3&DQGRWKHUSHUWLQHQWGRFXPHQWV

,QFOXVLRQ&ULWHULD
'HYLDWLRQVIURPLQFOXVLRQFULWHULDDUHQRWDOORZHGEHFDXVHWKH\FDQSRWHQWLDOO\MHRSDUGLVH
WKHVFLHQWLILFLQWHJULW\RIWKHVWXG\UHJXODWRU\DFFHSWDELOLW\RUVXEMHFWVDIHW\7KHUHIRUH
DGKHUHQFHWRWKHFULWHULDDVVSHFLILHGLQWKHSURWRFROLVHVVHQWLDO
6XEMHFWVHOLJLEOHIRUHQUROPHQWLQWKHVWXG\PXVWPHHWDOORIWKHIROORZLQJFULWHULD

,QIRUPHG FRQVHQW &DSDEOH RI JLYLQJ VLJQHG LQIRUPHG FRQVHQW DV GHVFULEHG LQ
6HFWLRQ ZKLFKLQFOXGHVFRPSOLDQFHZLWKWKHUHTXLUHPHQWVDQGUHVWULFWLRQVOLVWHG
LQWKHFRQVHQWIRUPDQGLQWKLVSURWRFRO

*HQGHUDQG$JH0DOHRUIHPDOHVXEMHFWVDJHG∀DQG\HDUVRIDJHDW9LVLW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
31
)HPDOHVXEMHFWLVHOLJLEOHWRSDUWLFLSDWHLIVKHLVQRWSUHJQDQWDVFRQILUPHGE\DQHJDWLYH
XULQHKXPDQFKRULRQLFJRQDGRWURSKLQ>K&*@WHVWQRWODFWDWLQJDQGDWOHDVWRQHRIWKH
IROORZLQJFRQGLWLRQVDSSOLHV
D
1RQUHSURGXFWLYHSRWHQWLDOGHILQHGDV
!
3UHPHQRSDXVDOIHPDOHVZLWKRQHRIWKHIROORZLQJ
!
'RFXPHQWHGWXEDOOLJDWLRQ
!
'RFXPHQWHGK\VWHURVFRSLFWXEDORFFOXVLRQSURFHGXUHZLWKIROORZ
XSFRQILUPDWLRQRIELODWHUDOWXEDORFFOXVLRQ
!
+\VWHUHFWRP\
!
'RFXPHQWHG%LODWHUDO2RSKRUHFWRP\
!
3RVWPHQRSDXVDOGHILQHGDVPRQWKVRIVSRQWDQHRXVDPHQRUUKHD>LQ
TXHVWLRQDEOHFDVHVDEORRGVDPSOHZLWKVLPXOWDQHRXVIROOLFOHVWLPXODWLQJ
KRUPRQH)6+DQGHVWUDGLROOHYHOVFRQVLVWHQWZLWKPHQRSDXVHUHIHUWR
ODERUDWRU\UHIHUHQFHUDQJHVIRUFRQILUPDWRU\OHYHOV@)HPDOHVRQKRUPRQH
UHSODFHPHQWWKHUDS\+57DQGZKRVHPHQRSDXVDOVWDWXVLVLQGRXEWZLOOEH
UHTXLUHGWRXVHRQHRIWKHKLJKO\HIIHFWLYHFRQWUDFHSWLRQPHWKRGVLIWKH\ZLVKWR
FRQWLQXHWKHLU+57GXULQJWKHVWXG\2WKHUZLVHWKH\PXVWGLVFRQWLQXH+57WR
DOORZFRQILUPDWLRQRISRVWPHQRSDXVDOVWDWXVSULRUWRVWXG\HQUROPHQW
E
5HSURGXFWLYHSRWHQWLDODQGDJUHHVWRIROORZRQHRIWKHRSWLRQVOLVWHGEHORZLQWKH
*6.0RGLILHG/LVWRI+LJKO\(IIHFWLYH0HWKRGVIRU$YRLGLQJ3UHJQDQF\LQ
)HPDOHVRI5HSURGXFWLYH3RWHQWLDO)53UHTXLUHPHQWVIURPGD\VSULRUWRWKH
ILUVWGRVHRIVWXG\PHGLFDWLRQDQGXQWLO:HHN9LVLW
*6.0RGLILHG/LVWRI+LJKO\(IIHFWLYH0HWKRGVIRU$YRLGLQJ3UHJQDQF\LQ)HPDOHV
RI5HSURGXFWLYH3RWHQWLDO)53
7KLVOLVWGRHVQRWDSSO\WR)53ZLWKVDPHVH[SDUWQHUVZKHQWKLVLVWKHLUSUHIHUUHGDQG
XVXDOOLIHVW\OHRUIRUVXEMHFWVZKRDUHDQGZLOOFRQWLQXHWREHDEVWLQHQWIURPSHQLOH
YDJLQDOLQWHUFRXUVHRQDORQJWHUPDQGSHUVLVWHQWEDVLV

&RQWUDFHSWLYHVXEGHUPDOLPSODQWWKDWPHHWVWKH623HIIHFWLYHQHVVFULWHULD
LQFOXGLQJDUDWHRIIDLOXUHSHU\HDUDVVWDWHGLQWKHSURGXFWODEHO

,QWUDXWHULQHGHYLFHRULQWUDXWHULQHV\VWHPWKDWPHHWVWKH623HIIHFWLYHQHVVFULWHULD
LQFOXGLQJDUDWHRIIDLOXUHSHU\HDUDVVWDWHGLQWKHSURGXFWODEHO>+DWFKHU
D@

2UDO&RQWUDFHSWLYHHLWKHUFRPELQHGRUSURJHVWRJHQDORQH>+DWFKHUD@

,QMHFWDEOHSURJHVWRJHQ>+DWFKHUD@

&RQWUDFHSWLYHYDJLQDOULQJ>+DWFKHUD@

3HUFXWDQHRXVFRQWUDFHSWLYHSDWFKHV>+DWFKHUD@

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
32

0DOHSDUWQHUVWHULOL]DWLRQZLWKGRFXPHQWDWLRQRID]RRVSHUPLDSULRUWRWKHIHPDOH
VXEMHFW
VHQWU\LQWRWKHVWXG\DQGWKLVPDOHLVWKHVROHSDUWQHUIRUWKDWVXEMHFW
>+DWFKHUD@

0DOHFRQGRPFRPELQHGZLWKDYDJLQDOVSHUPLFLGHIRDPJHOILOPFUHDPRU
VXSSRVLWRU\>+DWFKHUE@

7KHVHDOORZHGPHWKRGVRIFRQWUDFHSWLRQDUHRQO\HIIHFWLYHZKHQXVHG
FRQVLVWHQWO\FRUUHFWO\DQGLQDFFRUGDQFHZLWKWKHSURGXFWODEHO7KHLQYHVWLJDWRU
LVUHVSRQVLEOHIRUHQVXULQJWKDWVXEMHFWVXQGHUVWDQGKRZWRSURSHUO\XVHWKHVH
PHWKRGVRIFRQWUDFHSWLRQ

7\SHRIVXEMHFW
D
6XEMHFWV ZLWK GRFXPHQWHG SK\VLFLDQ¶V GLDJQRVLV RI DVWKPD   \HDU
XQVDWLVIDFWRULO\FRQWUROOHGDVWKPD$&7DW9LVLWDQG9LVLWWUHDWHGE\
,&6DORQHDQGLQWHQGHGWREHWUHDWHGE\,&6/$%$PDLQWHQDQFHWKHUDS\
E
)UDQFH2QO\$VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\RQO\LIHLWKHU
DIILOLDWHGWRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\

&XUUHQW $VWKPD 7KHUDS\ $OO VXEMHFWV PXVW EH SUHVFULEHG PDLQWHQDQFH WKHUDS\
DQG UHFHLYLQJ ,&6 DORQH ZLWKRXW /$%$ IRU DW OHDVW  ZHHNV SULRU WR 9LVLW 
5DQGRPLVDWLRQYLVLW
2WKHUEDFNJURXQGDVWKPDPHGLFDWLRQVXFKDVDQWLOHXNRWULHQHVRUWKHRSK\OOLQHLV
SHUPLWWHGDVDQDOWHUQDWLYHWR,&6DORQHLILQLWLDWHGDWOHDVWZHHNVSULRUWRVFUHHQLQJ
YLVLW9LVLW

6XEMHFW TXHVWLRQQDLUHV 6XEMHFWV PXVW EH DEOH WR FRPSOHWH WKH TXHVWLRQQDLUHV
WKHPVHOYHV

([FOXVLRQ&ULWHULD
'HYLDWLRQV IURP H[FOXVLRQ FULWHULD DUH QRW DOORZHG EHFDXVH WKH\ FDQ SRWHQWLDOO\
MHRSDUGLVHWKHVFLHQWLILFLQWHJULW\RIWKHVWXG\UHJXODWRU\DFFHSWDELOLW\RUVXEMHFWVDIHW\
7KHUHIRUHDGKHUHQFHWRWKHFULWHULDDVVSHFLILHGLQWKHSURWRFROLVHVVHQWLDO
6XEMHFWVPHHWLQJDQ\RIWKHIROORZLQJFULWHULDPXVWQRWEHHQUROOHGLQWKHVWXG\
 +LVWRU\RI/LIHWKUHDWHQLQJDVWKPD 'HILQHGIRUWKLVSURWRFRODVDQDVWKPDHSLVRGH
WKDWUHTXLUHGLQWXEDWLRQDQGRUZDVDVVRFLDWHGZLWKK\SHUFDSQHDUHVSLUDWRU\DUUHVWRU
K\SR[LFVHL]XUHVZLWKLQWKHODVWPRQWKV EHIRUH9LVLWDQG9LVLW
 6XEMHFWVKDYLQJDVHYHUHDQGXQVWDEOHDVWKPD ZLWK$&7 VFRUHDW9LVLWDQG
DW9LVLW DQGRUD KLVWRU\RIUHSHDWHGVHYHUHH[DFHUEDWLRQV\HDUDQGRUDVHYHUH
H[DFHUEDWLRQLQWKHSUHYLRXVZHHNVEHIRUH9LVLWDQG9LVLW

&23'5HVSLUDWRU\'LVHDVH$VXEMHFWPXVWQRWKDYHFXUUHQWHYLGHQFHRUGLDJQRVLV
RIFKURQLFREVWUXFWLYH SXOPRQDU\GLVHDVHDW9LVLW

&XUUHQWRUIRUPHUFLJDUHWWHVPRNHUVZLWKDKLVWRU\RIFLJDUHWWHVPRNLQJRI
SDFN\HDUVDWVFUHHQLQJ9LVLW>QXPEHURISDFN\HDUV QXPEHURIFLJDUHWWHVSHU

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
33
GD\[QXPEHURI\HDUVVPRNHGHJFLJDUHWWHVSHUGD\IRU\HDUVRU
FLJDUHWWHVSHUGD\IRU\HDUV@
 2WKHU GLVHDVHVDEQRUPDOLWLHV 6XEMHFWV ZLWK KLVWRULFDO RU FXUUHQW HYLGHQFH RI
XQFRQWUROOHGRUFOLQLFDOO\VLJQLILFDQWGLVHDVHDW9LVLWDQGDW9LVLW6LJQLILFDQWLV
GHILQHGDVDQ\GLVHDVHWKDWLQWKHRSLQLRQRIWKH,QYHVWLJDWRUZRXOGSXW WKHVDIHW\RI
WKHVXEMHFWDWULVNWKURXJKSDUWLFLSDWLRQRUZKLFKZRXOGDIIHFWWKHHIILFDF\RUVDIHW\
DQDO\VLVLIWKHGLVHDVHFRQGLWLRQH[DFHUEDWHGGXULQJWKHVWXG\
 6XEMHFWV ZLWK D KLVWRU\ RI DGYHUVH UHDFWLRQ LQFOXGLQJ LPPHGLDWH RU GHOD\HG
K\SHUVHQVLWLYLW\ WR DQ\ LQWUDQDVDO LQKDOHG RU V\VWHPLF FRUWLFRVWHURLG DQG /$%$
WKHUDS\ DQG WR FRPSRQHQWV RI WKH LQKDODWLRQ SRZGHU HJ ODFWRVH PDJQHVLXP
VWHDUDWHDW9LVLWDQGDW9LVLW,QDGGLWLRQVXEMHFWVZLWKDKLVWRU\RIVHYHUHPLON
SURWHLQDOOHUJ\WKDWLQWKHRSLQLRQRIWKH,QYHVWLJDWRUFRQWUDLQGLFDWHVWKHVXEMHFW¶V
SDUWLFLSDWLRQZLOODOVREHH[FOXGHG
 ,QYHVWLJDWLRQDO0HGLFDWLRQV$VXEMHFWPXVWQRWKDYHXVHGDQ\LQYHVWLJDWLRQDOGUXJ
ZLWKLQ  GD\V SULRU WR 9LVLW  RU ZLWKLQ ILYH KDOIOLYHV Wò RI WKH SULRU
LQYHVWLJDWLRQDO VWXG\ ZKLFKHYHU LV ORQJHU RI WKH WZR LI XQVXUH GLVFXVV ZLWK WKH
PHGLFDOPRQLWRUSULRUWRVFUHHQLQJ
 &KURQLF XVHU RI V\VWHPLF FRUWLFRVWHURLGV $ VXEMHFW ZKR LQ WKH RSLQLRQ RI WKH
,QYHVWLJDWRU LV FRQVLGHUHG WR EH D FKURQLF XVHU RI V\VWHPLF FRUWLFRVWHURLGV IRU
UHVSLUDWRU\RURWKHULQGLFDWLRQVLIXQVXUHGLVFXVVZLWKWKHPHGLFDOPRQLWRUSULRUWR
VFUHHQLQJDW9LVLW
 6XEMHFWV WUHDWHG E\ WKH PRQRFORQDO DQWLERG\ RPDOL]XPDE ;RODLU
RU
PHSROL]XPDE1XFDOD DW9LVLW7UHDWPHQWZLWK;RODLURU1XFDODLVQRWDOORZHG
GXULQJWKHVWXG\
 6XEMHFWVLQYROYHGLQRWKHUFOLQLFDOWULDOVDW9LVLW
 $IILOLDWLRQZLWK,QYHVWLJDWRU6LWH ,VDQLQYHVWLJDWRUVXELQYHVWLJDWRUVWXG\
FRRUGLQDWRUHPSOR\HHRIDSDUWLFLSDWLQJLQYHVWLJDWRURUVWXG\VLWHRULPPHGLDWH
IDPLO\PHPEHURIWKHDIRUHPHQWLRQHGWKDWLVLQYROYHGLQWKLVVWXG\
 6XEMHFWVZKRSODQWRPRYHDZD\IURPWKHJHRJUDSKLFDODUHDZKHUHWKHVWXG\LV
EHLQJFRQGXFWHGGXULQJWKHVWXG\

6FUHHQLQJ%DVHOLQH)DLOXUHV
$SSUR[LPDWHO\  VXEMHFWV ZLOO EH VFUHHQHG DV  VXEMHFWV DUH SODQQHG WR EH
UDQGRPLVHGDQGDVFUHHQIDLOXUHUDWHLVH[SHFWHG
!
6FUHHQIDLOXUHVDUHGHILQHGDVVXEMHFWVZKRFRQVHQWWRSDUWLFLSDWHLQWKHFOLQLFDOWULDO
EXWDUHQHYHUVXEVHTXHQWO\UDQGRPL]HG ,QRUGHUWRHQVXUHWUDQVSDUHQWUHSRUWLQJRI
VFUHHQIDLOXUHVXEMHFWVPHHWWKH&RQVROLGDWHG6WDQGDUGVRI5HSRUWLQJ7ULDOV
&216257SXEOLVKLQJUHTXLUHPHQWVDQGUHVSRQGWRTXHULHVIURP5HJXODWRU\
DXWKRULWLHVDPLQLPDOVHWRIVFUHHQIDLOXUHLQIRUPDWLRQLVUHTXLUHGLQFOXGLQJ
'HPRJUDSK\6FUHHQ)DLOXUHGHWDLOV(OLJLELOLW\&ULWHULDDQGDQ\6HULRXV$GYHUVH
(YHQWVUHODWHGWRVWXG\SDUWLFLSDWLRQ
3DWLHQWVWKDWIDLOVFUHHQLQJPD\EHUHVFUHHQHGRQO\XSRQDSSURYDOE\WKHPHGLFDOPRQLWRU

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
34

:LWKGUDZDO6WRSSLQJ&ULWHULD

6XEMHFWV/RVWWR)ROORZXS
7KHIROORZLQJDFWLRQVPXVWEHWDNHQLQUHODWLRQWRDVXEMHFWZKRIDLOVWRDWWHQGWKHFOLQLF
IRUDUHTXLUHGVWXG\YLVLW
!
7KHVLWHPXVWDWWHPSWWRFRQWDFWWKHVXEMHFWDQGUHVFKHGXOHWKHPLVVHGYLVLWDV
VRRQDVSRVVLEOH
!
7KHVLWHPXVWFRXQVHOWKHVXEMHFWRQWKHLPSRUWDQFHRIPDLQWDLQLQJWKHDVVLJQHG
YLVLWVFKHGXOHDQGDVFHUWDLQZKHWKHURUQRWWKHVXEMHFWZLVKHVWRDQGRUVKRXOG
FRQWLQXHLQWKHVWXG\
!
,QFDVHVZKHUHWKHVXEMHFWLVGHHPHGµORVWWRIROORZXS¶WKHLQYHVWLJDWRURU
GHVLJQHHPXVWPDNHHYHU\HIIRUWWRUHJDLQFRQWDFWZLWKWKHVXEMHFWZKHUH
SRVVLEOHWHOHSKRQHFDOOVDQGLIQHFHVVDU\DFHUWLILHGOHWWHUWRWKHVXEMHFW¶VODVW
NQRZQPDLOLQJDGGUHVVRUORFDOHTXLYDOHQWPHWKRGV7KHVHFRQWDFWDWWHPSWV
VKRXOGEHGRFXPHQWHGLQWKHVXEMHFW¶VPHGLFDOUHFRUG
!
6KRXOGWKHVXEMHFWFRQWLQXHWREHXQUHDFKDEOHRQO\WKHQZLOOKHVKHEH
FRQVLGHUHGWRKDYHZLWKGUDZQIURPWKHVWXG\ZLWKDSULPDU\UHDVRQRI³/RVWWR
)ROORZXS´

6XEMHFW:LWKGUDZDOE\,QYHVWLJDWRURU6HOIZLWKGUDZDO
6XEMHFWV PD\EHZLWKGUDZQIURPVWXG\WUHDWPHQWDWDQ\WLPHE\WKH,QYHVWLJDWRULILWLV
FRQVLGHUHGWREHGHWULPHQWDOIRUWKHPWRFRQWLQXHWKHVWXG\WUHDWPHQWRUPD\GLVFRQWLQXH
DVXEMHFWIURPWKHVWXG\DWKLVRUKHUGLVFUHWLRQ,IDVXEMHFWZLWKGUDZVIURPWKHVWXG\
KHVKHPD\UHTXHVWGHVWUXFWLRQRIDQ\VDPSOHVWDNHQDQGWKH,QYHVWLJDWRUPXVWGRFXPHQW
WKLVLQWKHVLWHVWXG\UHFRUGV
7KHIROORZLQJFULWHULDZLOOFDXVHDVXEMHFWWREHZLWKGUDZQIURPLQYHVWLJDWLRQDO
SURGXFW,3EXWHYHU\HIIRUWVKRXOGEHPDGHWRNHHS WKH6XEMHFWLQWKHVWXG\
!
$VXEMHFWEHFRPHVSUHJQDQW
!
$VXEMHFWPHHWVWKH/LYHU6WRSSLQJ&ULWHULDDVGHILQHGLQ6HFWLRQ
!
$VXEMHFWPHHWVWKH47FVWRSSLQJFULWHULDDVGHILQHGLQ6HFWLRQ
,IWKHVXEMHFWFKRRVHVWRZLWKGUDZIURPWKHVWXG\DOOVWXG\UHODWHGPHGLFDWLRQVDQGRWKHU
VWXG\UHODWHGPDWHULDOVVKRXOGEHUHWXUQHGWRWKHVLWHE\WKHVXEMHFW$Q(DUO\:LWKGUDZDO
9LVLWVKRXOGEHFRQGXFWHGZLWKLQKRXUV RIWKHVXEMHFWVWRSSLQJVWXG\PHGLFDWLRQ
6HFWLRQ 7LPHDQG(YHQW7DEOH,QWKHHYHQWDVXEMHFWZLWKGUDZVDWRUGXULQJD
VFKHGXOHGYLVLWDQ(DUO\:LWKGUDZDO9LVLWLVQRWUHTXLUHGKRZHYHUDOOVWXG\SURFHGXUHV
VFKHGXOHGDWDQ(DUO\:LWKGUDZDO9LVLWPXVWEHSHUIRUPHGDWWKLVYLVLWLQVWHDG
7KHSULPDU\UHDVRQIRUVWXG\WUHDWPHQWGLVFRQWLQXDWLRQRUVWXG\ZLWKGUDZDOZLOOEH
UHFRUGHGLQWKHHOHFWURQLF&DVH5HSRUW)RUPH&5)DQGDQ\GDWDFROOHFWHGXSXQWLOWKH
SRLQWRIZLWKGUDZDOZLOOEHXVHGLQWKHGDWDDQDO\VHV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
35
6SHFLILFUHJDUGVKRXOGEHJLYHQWRGLVWLQJXLVKLQJZLWKGUDZDOVGXHWR$'5V 6$(VDQG
SURWRFRO GHYLDWLRQ IROORZLQJ FRQVXOWDWLRQ ZLWK WKH PHGLFDO PRQLWRU 7KH ,QYHVWLJDWRU
ZLOOUHFRUGWKHSULPDU\UHDVRQLQWKHH&5)
6XEMHFWVZLWKGUDZQIURPWKHVWXG\ZLOOQRWEHUHSODFHG
6XEMHFWV ZKR H[SHULHQFH DQ DVWKPD H[DFHUEDWLRQ GXULQJ WKH 7UHDWPHQW 3HULRG FDQ
FRQWLQXHLQWKHVWXG\DWWKHGLVFUHWLRQRIWKHLU,QYHVWLJDWRU

/LYHU&KHPLVWU\6WRSSLQJ&ULWHULD
/LYHUFKHPLVWU\VWRSSLQJDQGLQFUHDVHGPRQLWRULQJFULWHULD KDYHEHHQGHVLJQHGWR
DVVXUHVXEMHFWVDIHW\DQGHYDOXDWHOLYHUHYHQW HWLRORJ\ LQDOLJQPHQWZLWKWKH)'$
SUHPDUNHWLQJFOLQLFDOOLYHUVDIHW\JXLGDQFH
KWWSZZZIGDJRYGRZQORDGV'UXJV*XLGDQFH&RPSOLDQFH5HJXODWRU\,QIRUPDWLRQ*XLG
DQFHV8&0SGI
3KDVH,,,,9/LYHU&KHPLVWU\6WRSSLQJDQG,QFUHDVHG0RQLWRULQJ$OJRULWKP
Continue Study Treatment 
Discontinue Study Treatment 
3OXV
Bilirubin≥2x
ULN (>35% 
direct) RUSOXV
INR>1.5, if 
measured*
3RVVLEOH
+\¶V /DZ
ALT≥3xULN
ALT
≥8xULN
3OXV
Symptoms of 
liver injury
or 
hypersensitivity
No
Yes
Yes
Yes
No
No
No
See algorithm 
for continued 
therapy with 
increased liver 
chemistry 
monitoring
Yes
*INR value not applicable to subjects on anticoagulants 
ALT 
≥3xULN 
but 
<8xULN
Yes
 0XVWUHIHUWR/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWVVHFWLRQLQWKH$SSHQGL[
 5HSRUWDVDQ6$(LISRVVLEOH+\¶V /DZFDVHALT≥3xULN DQGBilirubin≥2xULN (>35% direct)  RU
INR>1.5, if measured*

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
36
3KDVH,,,,9/LYHU&KHPLVWU\,QFUHDVHG0RQLWRULQJ$OJRULWKPZLWK&RQWLQXHG
7KHUDS\IRU$/7∀[8/1EXW[8/1
Continue Study Treatment   and   Monitor Liver Chemistry
Discontinue Study Treatment 
ALT≥5xULN 
but <8xULN
+ bili <2xULN +
no symptoms
No
 0XVWUHIHUWR/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWVVHFWLRQLQWKH$SSHQGL[
Yes
ALT ≥3xULN 
but <5xULN
+ bili <2xULN  +
no symptoms
Able to 
monitor  
weekly 
for  ≥2 
weeks
Persists for 
≥2 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
No
No
Able to 
monitor  
weekly 
for  ≥4 
weeks
Persists for 
≥4 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
Yes
ALT ≥5xULN 
ALT <5xULN 
Yes
Yes
*INR value not applicable to subjects on anticoagulants 
 0XVWUHIHUWR/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWVVHFWLRQLQWKH$SSHQGL[
 5HSRUWDVDQ6$(LISRVVLEOH+\¶V /DZFDVHALT≥3xULN DQGBilirubin≥2xULN (>35% direct)  RU
INR>1.5, if measured*
/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWV6HFWLRQFDQEHIRXQGLQ
$SSHQGL[

6WXG\7UHDWPHQW5HVWDUWRU 5HFKDOOHQJH
6WXG\WUHDWPHQWUHVWDUWRUUHFKDOOHQJHDIWHUOLYHUFKHPLVWU\VWRSSLQJFULWHULDPHWE\DQ\
VXEMHFWSDUWLFLSDWLQJLQWKLVVWXG\LVQRWDOORZHG

47F6WRSSLQJ&ULWHULD
$Q(&*LVQRWUHTXLUHGSULRUWRHQWHULQJWKLVVWXG\7KHUHDUHQRRWKHUUHJXODU(&*V
UHTXLUHGE\WKLVSURWRFRO,IKRZHYHUZKLOHDVXEMHFWLVUHFHLYLQJVWXG\PHGLFDWLRQDQ
(&*LVSHUIRUPHGDVSDUWRIWKHQRUPDOFOLQLFDOSUDFWLFHDQGDSURORQJHG47LQWHUYDOLV
GHWHFWHG WKH IROORZLQJ DVVHVVPHQWV IRU ZLWKGUDZDO IURP WKH VWXG\ DUH UHTXLUHG DIWHU
GLVFXVVLRQEHWZHHQ,QYHVWLJDWRUDQGWKHPHGLFDOPRQLWRU
)RUDOOVXEMHFWV
$VXEMHFWZKRPHHWVHLWKHURIWKHEXOOHWHGFULWHULDEHORZZLOOEHZLWKGUDZQIURPWKH
VWXG\
!
47F!PVHF258QFRUUHFWHG 47!PVHF
!
,QFUHDVHLQ47F!PVHFGHWHFWHGFRPSDUHGWRDSUHYLRXV(&*

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
37
)RUSDWLHQWVZLWKXQGHUO\LQJEXQGOHEUDQFKEORFNIROORZWKHGLVFRQWLQXDWLRQFULWHULD
OLVWHGEHORZ
%DVHOLQH47FZLWK%XQGOH%UDQFK%ORFN
'LVFRQWLQXDWLRQ47FZLWK%XQGOH
%UDQFK%ORFN
PVHF
!PVHF
± PVHF
PVHF
7KH47FVKRXOGEHEDVHGRQVLQJOHRUDYHUDJHG47FYDOXHVRIWULSOLFDWH
HOHFWURFDUGLRJUDPVREWDLQHGRYHUDEULHIHJPLQXWHUHFRUGLQJSHULRG

6XEMHFWDQG6WXG\&RPSOHWLRQ
$FRPSOHWHGVXEMHFWLVRQHZKRKDVFRPSOHWHGDOOVWXG\YLVLWV7KHHQGRIWKHVWXG\LV
GHILQHGDVWKHODVWVXEMHFW¶VODVWYLVLW

678'<75($70(17

,QYHVWLJDWLRQDO3URGXFWDQG2WKHU6WXG\7UHDWPHQW
7KHWHUPµVWXG\WUHDWPHQW¶LVXVHGWKURXJKRXWWKHSURWRFROWRGHVFULEHDQ\FRPELQDWLRQ
RISURGXFWVUHFHLYHGE\WKHVXEMHFWDVSHUWKHSURWRFROGHVLJQ6WXG\WUHDWPHQWPD\
WKHUHIRUHUHIHUWRWKHLQGLYLGXDOVWXG\WUHDWPHQWVRUWKHFRPELQDWLRQRIWKRVHVWXG\
WUHDWPHQWV
$OOVXEMHFWVZLOOUHFHLYHWKHDVWKPDPHGLFDWLRQWREHXVHGGXULQJWKHVWXG\IURPWKH
LQYHVWLJDWRUVLWH
*OD[R6PLWK.OLQH&OLQLFDO7ULDOV6XSSOLHVZLOOSURYLGHWKHLQYHVWLJDWLRQDOSURGXFWV
))9,5HOYDU(OOLSWDDQGFRPSDUDWLYHWUHDWPHQWVLH9LDQL6HUHWLGH'LVNXV6\PELFRUW
7XUEXKDOHU5HVFXHPHGLFDWLRQ6DOEXWDPROZLOOEHSURYLGHGORFDOO\E\*6.LQHDFK
FRXQWU\
1HZ,&6/$%$'3,RU'3,FRSLHVRIH[LVWLQJPDUNHWHG,&6/$%$ LIDQ\DWWKHWLPHRI
WKHVWXG\ ZLOOQRWEHFRQVLGHUHGLQWKLV WULDO
(DFKVXEMHFWUDQGRPLVHGWRWKH))9,DUPZLOOEHLQVWUXFWHGWRDGPLQLVWHUWKHVWXG\
PHGLFDWLRQRQFHGDLO\E\UHDGLQJWKHOHDIOHWDQGGHPRQVWUDWLRQRILWXVHDWWKHVDPH
WLPHRIWKHGD\IRUWKHGXUDWLRQRIWKHWUHDWPHQWSHULRG(DFKVXEMHFWZLOOEHDGYLVHGWR
DGKHUHWR))9,GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\ VWDUWLQJZLWK))9,PFJPFJ
7KHLQYHVWLJDWRU RUDSSURSULDWHO\TXDOLILHGGHVLJQHH PD\LQFUHDVHWKHGRVHRI))9,
DFFRUGLQJWRWKHVXEMHFWV¶UHVSRQVH
(DFKVXEMHFWLQLWLDWLQJRWKHU,&6/$%$PDLQWHQDQFHWKHUDS\ZLOOEHUHPLQGHGDERXWWKH
WHFKQLTXHVRIKRZWRXVHWKHLUPDLQWHQDQFHPHGLFDWLRQE\UHDGLQJWKHOHDIOHWDQG
GHPRQVWUDWLRQRILWXVHDQGWKHFRUUHFWGRVLQJ(DFKVXEMHFWZLOOEHDGYLVHGWRDGKHUHWR

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
38
,&6/$%$GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\VWDUWLQJZLWK)36PFJPFJRU
ZLWK%8')PFJPFJDFFRUGLQJWRWKH,QYHVWLJDWRU¶VGHFLVLRQ7KH,QYHVWLJDWRU
PD\LQFUHDVHWKHGRVHRIHDFKSURGXFWDFFRUGLQJWRWKHVXEMHFWV¶UHVSRQVH
$GHVFULSWLRQRIWKHLQYHVWLJDWLRQDOWUHDWPHQWVLVSURYLGHGEHORZ
7DEOH
'HVFULSWLRQRI)OXWLFDVRQH)XURDWH9LODQWHURO,QKDODWLRQ3RZGHU'U\
3RZGHU,QKDOHUDQG SHUPLWWHGFRPSDUDWLYHWUHDWPHQWV
&RPSRXQG
)RUPXODWLRQ
)OXWLFDVRQH
)XURDWH9LODQWHURO
)LUVW VWULS ))  PFJ RU  PFJ EOHQGHG ZLWK
ODFWRVH
6HFRQGVWULS9LODQWHUROPFJEOHQGHGZLWKODFWRVH
DQGPDJQHVLXPVWHDUDWH
'RVDJH)RUP
'3,(OOLSWD± GRVHVSHUGHYLFH
8QLW'RVH6WUHQJWK
PFJPFJRUPFJPFJSHUDFWXDWLRQ
5RXWHRI$GPLQLVWUDWLRQ
,QKDOHG
&RPSRXQG
)RUPXODWLRQ
)OXWLFDVRQHSURSLRQDWH6DOPHWHURO
)3PFJRUPFJEOHQGHGZLWKODFWRVH
6DOPHWHUROPFJEOHQGHGZLWKODFWRVH
'RVDJH)RUP
'3,'LVNXV± GRVHVSHUGHYLFH
8QLW'RVH6WUHQJWK
PFJPFJRUPFJPFJSHUDFWXDWLRQ
5RXWHRI$GPLQLVWUDWLRQ
,QKDOHG
&RPSRXQG
)RUPXODWLRQ
%XGHVRQLGH)RUPRWHURO)XPDUDWH
%XGHVRQLGH  PFJ RU  PFJ  EOHQGHG ZLWK
ODFWRVH
)RUPRWHURO)XURDWHPFJRUPFJEOHQGHGZLWK
ODFWRVH
'RVDJH)RUP
'3,7XUEXKDOHU RUGRVHVPFJPFJRU
PFJPFJSHUGHYLFH
8QLW'RVH6WUHQJWK
PFJPFJRUPFJPFJSHUDFWXDWLRQ
5RXWHRI$GPLQLVWUDWLRQ
,QKDOHG
 PDJQHVLXPVWHDUDWHZZRIWRWDOGUXJSURGXFW
7KHVXEMHFW¶VXVHRIVKRUWUDSLGDFWLQJEHWDDJRQLVWEURQFKRGLODWRUZLOOEHDVVHVVHGDVLW
ZRXOGEHLQURXWLQHFDUHDQGLIUHTXLUHGUHVFXHPHGLFDWLRQZLOOEHSUHVFULEHGWRVXEMHFWV
WRXVHDVQHHGHGWKURXJKRXWWKHVWXG\IRUUHOLHIRIDVWKPDV\PSWRPVDVSHUXVXDOSUDFWLFH

0HGLFDO'HYLFHV
0HGLFDOGHYLFHVVSLURPHWHUVZLOOEHSURYLGHGE\*6.IRUXVHLQWKLVVWXG\+RZHYHU
QRQHRIWKHGHYLFHVSURYLGHGDUHPDQXIDFWXUHGE\RURQEHKDOIRI*6.

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
39

7UHDWPHQW$VVLJQPHQW
6XEMHFWVZLOOEHDVVLJQHGWRVWXG\WUHDWPHQWLQDFFRUGDQFHZLWKWKHUDQGRPLVDWLRQ
VFKHGXOH
6XEMHFWVZLOOEHUDQGRPL]HGWR RQHRIWKHIROORZLQJWUHDWPHQWJURXSV
!
))9,DVSHUGRVHJXLGDQFHEHORZ
!
8VXDOLQKDOHGGU\SRZGHU,&6/$%$IL[HGFRPELQDWLRQIRUDVWKPDPDLQWHQDQFH
WKHUDS\OLPLWHGWR 6HUHWLGH9LDQL 'LVNXVRU6\PELFRUW 7XUEXKDOHUDFFRUGLQJWR
XVXDOSK\VLFLDQ¶VSUHVFULSWLRQ
!
1RWH7RPDLQWDLQFRQVLVWHQF\DFURVVFRXQWULHVWKHFKRLFHRIXVXDOLQKDOHGGU\
SRZGHU,&6/$%$IL[HGFRPELQDWLRQZLOOEHOLPLWHGWR6HUHWLGH9LDQL'LVNXV
)36PFJPFJRUPFJPFJRU6\PELFRUW7XUEXKDOHU %8')
PFJPFJRUPFJPFJ6RPH FRXQWULHVKDYH RWKHU,&6/$%$IL[HG
FRPELQDWLRQVDQGRWKHUJHQHULFYHUVLRQVRI)36DQG%8')DYDLODEOHIRUWKH
WUHDWPHQWRISDWLHQWVZLWKDVWKPDEXWWKHVHZLOOQRWEHSHUPLWWHGLQWKLVVWXG\
$GGLWLRQDOO\VRPH FRXQWULHVKDYH RSWLRQVIRUDORZHU GRVHRI9LDQL'LVNXV)36
PFJPFJDQG6\PELFRUW7XUERKDOHU %8')PFJPFJEXWWKHVHZLOO
QRWEHSHUPLWWHGLQWKLVVWXG\
'RVH*XLGDQFH
)RUVXEMHFWVUDQGRPLVHGWR))9,,QYHVWLJDWRURUVXLWDEO\TXDOLILHGGHVLJQHH FDQ PDNH
GRVLQJGHFLVLRQEDVHGRQWKHJXLGDQFHEHORZ
!
))9,PFJPFJGRVH RQFHDGD\LVDSSUR[LPDWHO\HTXLYDOHQWWRIOXWLFDVRQH
SURSLRQDWHVDOPHWHURO)36PHGLXPGRVHPFJPFJDQGWR
EXGHVRQLGHIRUPRWHURO%8')PHGLXPGRVHPFJPFJWZLFHDGD\6HH
7DEOH IRUIXUWKHUJXLGDQFHIRUGRVHVFRQYHUVLRQIRURWKHUFRUWLFRVWHURLGV
!
))9,PFJPFJGRVHRQFHDGD\LVDSSUR[LPDWHO\HTXLYDOHQWWR
IOXWLFDVRQHSURSLRQDWHVDOPHWHUROKLJKGRVHPFJPFJDQGWR
EXGHVRQLGHIRUPRWHUROKLJKGRVHPFJPFJWZLFHDGD\6HH7DEOH IRU
JXLGDQFHIRUGRVHFRQYHUVLRQIRURWKHUFRUWLFRVWHURLGV
!
6WDUWLQJGRVHVDUHPFJPFJRQFHGDLO\ IRU))9,PFJPFJWZLFH
GDLO\IRU)36DQG PFJPFJWZLFHGDLO\IRU%8')

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
40
7DEOH
,&6/$%$'DLO\'RVH6P3&6HUHWLGH9LDQL 'LVNXV6\PELFRUW
7XUEXKDOHU
)RUPXODWLRQ
,QKDOHU'HYLFHV
'RVHV$YDLODEOHPFJ
,&6/$%$DQG
,QKDODWLRQVGD\
)OXWLFDVRQH
SURSLRQDWHVDOPHWHURO
'3,'LVNXV
LQKDODWLRQ[
0HGLXPGRVH
+LJKGRVH
%XGHVRQLGHIRUPRWHURO
'3,7XUEXKDOHU
LQKDODWLRQV[
0HGLXPGRVH
+LJKGRVH
,QIRUPDWLRQH[WUDFWHGIURP*,1$ UHIHUWR*,1$IRUIXUWKHUJXLGDQFH
)RUSDWLHQWVZLWKPRGHUDWHWRVHYHUHKHSDWLFLPSDLUPHQWWKH PLFURJUDPVGRVH
VKRXOGEHXVHGDQGSDWLHQWVVKRXOGEHPRQLWRUHGIRUV\VWHPLFFRUWLFRVWHURLGUHODWHG
DGYHUVHUHDFWLRQVVHH6P3&

3ODQQHG'RVH$GMXVWPHQWV
6XEMHFWVIRUZKRPLWLVFRQVLGHUHGDSSURSULDWHQHFHVVDU\WRDGMXVWWUHDWPHQWFDQKDYH
WKHLUGRVHLQFUHDVHGIURPWKHVWDUWLQJGRVHDVZRXOGEHQRUPDOFOLQLFDOSUDFWLFHDWWKH
,QYHVWLJDWRU¶VGLVFUHWLRQ7KLVZLOOQRWUHTXLUHWKHVXEMHFWWREHZLWKGUDZQIURPWKH
VWXG\
,WLVQRWSHUPLWWHGIRUSDWLHQWVWREHVZLWFKHGWRDGLIIHUHQWWUHDWPHQWLHSDWLHQWV
UDQGRPLVHGWRWKHXVXDO,&6/$%$DUPFDQQRWFKDQJHWRDGLIIHUHQW,&6/$%$RU
UHFHLYH))9, 3DWLHQWVUDQGRPLVHGWRWKH))9,DUPFDQQRWUHFHLYHXVXDO,&6/$%$,I
DVZLWFKEHWZHHQSURGXFWVLVUHTXLUHGWKHSDWLHQWVKRXOGEHZLWKGUDZQIURPWKHVWXG\

%OLQGLQJ
7KLVVWXG\LVDQRSHQODEHOUDQGRPLVHGVWXG\

3DFNDJLQJDQG /DEHOLQJ
7KHFRQWHQWVRIWKHODEHOZLOOEHLQDFFRUGDQFHZLWKDOODSSOLFDEOHUHJXODWRU\
UHTXLUHPHQWV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
41

3UHSDUDWLRQ+DQGOLQJ6WRUDJH$FFRXQWDELOLW\
$OO))9,DQGFRPSDUDWLYH,&6/$%$PDLQWHQDQFHWKHUDS\SUHVFULEHGWKURXJKRXWWKH
VWXG\ZLOOEHGLVSHQVHGDWDQGFROOHFWHGIURPWKHLQYHVWLJDWRUVLWH
,QYHVWLJDWLRQDOSURGXFWPXVWEHVWRUHGLQDVHFXUHDUHDXQGHU WKHDSSURSULDWHSK\VLFDO
FRQGLWLRQVIRUWKHSURGXFW$OO'3,VFRQWDLQLQJ))9,PXVWEHVWRUHGDWDWHPSHUDWXUHRI
XSWR&%XGHVRQLGH)RUPRWHURO'3,VPXVWEHVWRUHGDWDWHPSHUDWXUHRIXSWR&
DQG)OXWLFDVRQH3URSLRQDWH6DOPHWHURO'3,VVWRUHGDW#&
$FFHVVWRDQGDGPLQLVWUDWLRQRIWKHLQYHVWLJDWLRQDOSURGXFWZLOOEHOLPLWHGWRWKH
LQYHVWLJDWRUDQGDXWKRULVHGVLWHVWDII,QYHVWLJDWLRQDOSURGXFWPXVWEHGLVSHQVHGRU
DGPLQLVWHUHGRQO\WRVXEMHFWVHQUROOHGLQWKHVWXG\DQGLQDFFRUGDQFHZLWKWKHSURWRFRO
$OOXVHGDQGXQXVHGVWXG\PHGLFDWLRQLQKDOHUV))9,RUXVXDO,&6/$%$DVWKPD
PDLQWHQDQFHWKHUDS\VKRXOGEHUHWXUQHGWRWKHLQYHVWLJDWRUVLWHZKHQWKHVXEMHFWVDWWHQG
IRUDYLVLW
$WWKHHQGRIWKHVWXG\DOOVWXG\VXSSOLHGVWXG\PHGLFDWLRQXVHGDQGXQXVHGSURYLGHG
WRLQYHVWLJDWRU VLWHVZLOOEHGHVWUR\HGIROORZLQJORFDOVWDQGDUGRSHUDWLQJSURFHGXUHV
H[FHSWZKHUHLWLVVXVSHFWHGWKDW(OOLSWDRU*6.'3,SDFNDJLQJLVGHIHFWLYH 7KHGHYLFH
DQGSDFNDJLQJVKRXOGEHUHWXUQHGWR*6.
'HWDLOVIRUERWK UHWXUQDQGGHVWUXFWLRQDQGRIVWXG\PHGLFDWLRQDUHIRXQGLQWKH6WXG\
5HIHUHQFH0DQXDO650
8QGHUQRUPDOFRQGLWLRQVRIKDQGOLQJDQGDGPLQLVWUDWLRQLQYHVWLJDWLRQDOSURGXFWLVQRW
H[SHFWHGWRSRVHVLJQLILFDQWVDIHW\ULVNVWRVLWHVWDII7DNHDGHTXDWHSUHFDXWLRQVWRDYRLG
GLUHFWH\HRUVNLQFRQWDFWDQGWKHJHQHUDWLRQRIDHURVROVRUPLVWV1RWLI\WKHPRQLWRURI
DQ\XQLQWHQWLRQDORFFXSDWLRQDOH[SRVXUH$0DWHULDO6DIHW\'DWD6KHHW06'6
GHVFULELQJWKHRFFXSDWLRQDOKD]DUGVDQGUHFRPPHQGHGKDQGOLQJSUHFDXWLRQVZLOOEH
SURYLGHGWRVLWHVWDIILIUHTXLUHGE\ORFDOODZVRUZLOORWKHUZLVHEHDYDLODEOHIURP*6.
XSRQUHTXHVW
,QDFFRUGDQFHZLWKORFDOUHJXODWRU\UHTXLUHPHQWVWKH,QYHVWLJDWRUGHVLJQDWHGVLWHVWDII
RUKHDGRIWKHPHGLFDOLQVWLWXWLRQZKHUHDSSOLFDEOHPXVWGRFXPHQWWKHDPRXQWRI
LQYHVWLJDWLRQDOSURGXFWGLVSHQVHGDQGRUDGPLQLVWHUHGWRVWXG\VXEMHFWVWKHDPRXQW
UHWXUQHGE\VWXG\VXEMHFWVDQGWKHDPRXQWUHFHLYHGIURPDQGUHWXUQHGWR*6.ZKHQ
DSSOLFDEOH3URGXFWDFFRXQWDELOLW\UHFRUGVPXVWEHPDLQWDLQHGWKURXJKRXWWKHFRXUVHRI
WKHVWXG\

,QYHVWLJDWLRQDO3URGXFW0DOIXQFWLRQ
$Q\LQYHVWLJDWLRQDOSURGXFWLQKDOHUWKDWIDLOVWRIXQFWLRQSURSHUO\PXVWEHLGHQWLILHGWR
*6.SHUVRQQHO'HWDLOVRIWKHIDLOXUHZLOOEHGRFXPHQWHGLQWKHH&5)(OOLSWDLQKDOHUV
ZLOO EHUHWXUQHGWR*6.IRUWHVWLQJ7KHVXEMHFWVKRXOGUHWXUQWKHLQKDOHUWRWKHFOLQLFDV
VRRQDVSRVVLEOHWRDYRLGPLVVLQJDQ\GRVHV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
42
7KHVLWHZLOOWKHQFRQWDFW*6.¶VLQWHUQDO,:56DOVRNQRZQDVWKH5HJLVWUDWLRQDQG
0HGLFDWLRQ2UGHULQJ6\VWHP>5$026@1* DQGREWDLQDQHZWUHDWPHQWSDFNQXPEHU
IRUWKLVVXEMHFWDQGGLVSHQVHDQHZVWXG\PHGLFDWLRQNLWIURPWKHVLWH
VLQYHVWLJDWLRQDO
SURGXFWVXSSO\DVLQVWUXFWHGSHUWKH,:56

&RPSOLDQFHZLWK6WXG\7UHDWPHQW$GPLQLVWUDWLRQ
:KHQWKHVXEMHFWVDWWHQGWKHLQYHVWLJDWRUVLWHWKH\ZLOOEHLQVWUXFWHGWRDGPLQLVWHUWKH
VWXG\PHGLFDWLRQRQFHGDLO\DWWKHVDPHWLPHRIWKHGD\IRUWKHGXUDWLRQRIWKHWUHDWPHQW
ZKHQUDQGRPLVHGWR))9,YLD(OOLSWD70 DQGWZLFHGDLO\RQWKHPRUQLQJDQGHYHQLQJ
ZKHQUDQGRPLVHGWR,&6/$%$ '3,'LVNXV70 RU7XUEXKDOHU$OOXVHGDQGXQXVHG
VWXG\PHGLFDWLRQLQKDOHUV))9,RUXVXDODVWKPDPDLQWHQDQFHWKHUDS\VKRXOGEH
UHWXUQHGWRWKHLQYHVWLJDWRUVLWHZKHQWKHVXEMHFWVFROOHFWSUHVFULSWLRQVRIVWXG\
PHGLFDWLRQ
2YHUDOOWUHDWPHQWFRPSOLDQFHZLWKVWXG\PHGLFDWLRQZLOOEHFDOFXODWHGIRUHDFKW\SHRI
LQKDOHUVHSDUDWHO\DV

7RWDOQXPEHURILQKDODWLRQVWDNHQLVWKHWRWDOQXPEHURIGRVHVWDNHQIURPDOOLQKDOHUV
GXULQJWKHWLPHSHULRGDVDVVHVVHGIURPGRVHFRXQWHUGDWDFROOHFWHGRQWKHH&5)

([SHFWHG,QKDODWLRQVLVWKHH[SHFWHGQXPEHURILQKDODWLRQVSHUGD\IRU(OOLSWD70
IRU'LVNXV70 DQGRUIRU7XUEXKDOHU70 GHSHQGLQJRQWKHGRVH

6WDUWGDWHDQG6WRSGDWHDUHWKHHDUOLHVWWUHDWPHQWVWDUWGDWHDQGWKHODWHVWWUHDWPHQW
VWRSGDWHUHVSHFWLYHO\IRUDOOLQKDOHUVXVHGLQWKHFDOFXODWLRQ
7UHDWPHQWFRPSOLDQFHZLOOEHDVVHVVHGIRUWKHSHULRGIURPUDQGRPLVDWLRQ'D\XQWLO
:HHN9LVLWIURP:HHN9LVLWXQWLO:HHN9LVLWDQGDOVRRYHUDOOIURP
UDQGRPLVDWLRQ'D\XQWLO:HHN 9LVLW
6XEMHFW¶VVHOIUHSRUWHGDGKHUHQFHWRPHGLFDWLRQZLOOEHHYDOXDWHGEDVHGRQDQDO\VLVRI
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHV DW
UDQGRPLVDWLRQ'D\DW:HHNDQGDW:HHN

7UHDWPHQWRI6WXG\7UHDWPHQW2YHUGRVH
$QRYHUGRVHZLOOEHGHILQHGDVWKHVXEMHFWUHFHLYLQJDQ\DPRXQWRI,3JUHDWHUWKDQWKH
PD[LPXPGRVHSHUPLWWHGE\WKHSURWRFROZKLFKUHVXOWVLQFOLQLFDOVLJQVRUV\PSWRPV
,QWKHHYHQWRIDQRYHUGRVHRIVWXG\PHGLFDWLRQWKH,QYHVWLJDWRUVKRXOGXVHFOLQLFDO
MXGJPHQWLQWUHDWLQJWKHRYHUGRVHDQGFRQWDFWWKHVWXG\PHGLFDOPRQLWRU
*OD[R6PLWK.OLQH*6.LVQRWUHFRPPHQGLQJVSHFLILFWUHDWPHQWJXLGHOLQHVIRURYHUGRVH
DQGWR[LFLW\PDQDJHPHQW7KH,QYHVWLJDWRUVKRXOGUHIHUWRWKHUHOHYDQWGRFXPHQWVIRU
GHWDLOHGLQIRUPDWLRQUHJDUGLQJZDUQLQJVSUHFDXWLRQVFRQWUDLQGLFDWLRQVDGYHUVHHYHQWV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
43
DQGRWKHUVLJQLILFDQWGDWDSHUWDLQLQJWRWKHVWXG\GUXJEHLQJXVHGLQWKLVVWXG\6XFK
GRFXPHQWVPD\LQFOXGHEXWQRWEHOLPLWHGWRWKH,%VRUHTXLYDOHQWGRFXPHQWSURYLGHG
E\*6.IRUVWXG\PHGLFDWLRQV

7UHDWPHQWDIWHUWKH(QGRIWKH6WXG\
7KHLQYHVWLJDWRULVUHVSRQVLEOHIRUHQVXULQJWKDWFRQVLGHUDWLRQKDVEHHQJLYHQWRWKHSRVW
VWXG\FDUHRIWKHSDWLHQW¶VPHGLFDOFRQGLWLRQ *6.ZLOOQRWSURYLGH SRVWVWXG\WUHDWPHQW

&RQFRPLWDQW0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
$OOUHVSLUDWRU\UHODWHGSUHVFULEHGDQGGLVSHQVHGFRQFRPLWDQWPHGLFDWLRQVWDNHQGXULQJ
WKHVWXG\ZLOOEHUHFRUGHG7KHPLQLPXPUHTXLUHPHQWLVWKDWGUXJWUDGHQDPHDQGWKH
GDWHVRISUHVFULELQJGLVSHQVLQJDQGFROOHFWLRQZLOOEHUHFRUGHG

3HUPLWWHG0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
$OOPHGLFDWLRQVIRUDVWKPDDQGRWKHUGLVRUGHUVWKDWDUHQRWFRQWUDLQGLFDWHGLQDVWKPDRU
OLVWHGDVDSURKLELWHGPHGLFDWLRQVHH6HFWLRQPD\EHFRQWLQXHGWKURXJKRXWWKH
VWXG\
$WFOLQLFDOGRVHVORZSODVPDFRQFHQWUDWLRQVRI))DQG9,DUHDFKLHYHGDIWHULQKDOHG
GRVLQJGXHWRH[WHQVLYHILUVWSDVVPHWDEROLVPDQGKLJKV\VWHPLFFOHDUDQFHPHGLDWHGE\
F\WRFKURPH3$LQWKHJXWDQGRUOLYHUDQ\FOLQLFDOO\VLJQLILFDQWGUXJLQWHUDFWLRQV
PHGLDWHGE\))RU9,DUHXQOLNHO\
$&<3$GUXJLQWHUDFWLRQVWXG\ZDVSHUIRUPHGLQKHDOWK\VXEMHFWVZLWKWKH))9,
FRPELQDWLRQDQG.HWRFRQD]ROH&RDGPLQLVWUDWLRQLQFUHDVHGPHDQ))$8&
DQG&PD[E\DQGUHVSHFWLYHO\7KHLQFUHDVHLQ))H[SRVXUHZDV
DVVRFLDWHGZLWKDUHGXFWLRQLQKZHLJKWHGPHDQVHUXPFRUWLVRO&R
DGPLQLVWUDWLRQLQFUHDVHGPHDQ9,$8&W¶DQG&PD[DQGUHVSHFWLYHO\7KH
LQFUHDVHLQ9,H[SRVXUHZDVQRWDVVRFLDWHGZLWKDQLQFUHDVHLQEHWDDJRQLVWUHODWHG
V\VWHPLFHIIHFWVRQKHDUWUDWHEORRGSRWDVVLXPRU47F)LQWHUYDO
&DUHLVDGYLVHGZKHQFRDGPLQLVWHULQJSRWHQWF\WRFKURPH3$LQKLELWRUVHJ
NHWRFRQD]ROHULWRQDYLUDVWKHUHLVSRWHQWLDOIRUDQLQFUHDVHGV\VWHPLFH[SRVXUHWRERWK
))DQG9,&RQVLGHUDWLRQVKRXOGEHJLYHQWRWKHFOLQLFDOVLWXDWLRQDQGWKHGXUDWLRQRI
WUHDWPHQWZLWKVXFKFRQFXUUHQWPHGLFDWLRQV

3URKLELWHG0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
!
6\VWHPLFFRUWLFRVWHURLGVH[FHSWLQFDVHRID VHYHUHDVWKPDH[DFHUEDWLRQ
!
0RQRFORQDODQWLERGLHV RPDOL]XPDE;RODLU DQGPHSROL]XPDE1XFDOD 

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
44

678'<$66(660(176$1'352&('85(6
7KH7LPHDQG(YHQWV7DEOHLVSURYLGHGLQ6HFWLRQ$OOVWXG\DVVHVVPHQWVVKRXOGEH
FRQGXFWHGE\WKH,QYHVWLJDWRURUKLVKHUTXDOLILHGGHVLJQHHXQOHVVRWKHUZLVHVSHFLILHGLQ
WKHSURWRFRORU6503OHDVHUHIHUWRWKH650IRUWKHVXJJHVWHGRUGHURIDVVHVVPHQWV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
45

7LPHDQG(YHQWV7DEOH
Study Visits
Visit 1*
Screening#
Visit 2*
Randomisation
Visit 3
Phone call 1
Visit 4**
Visit 5
Phone call 2
Visit 6
Early Withdrawal
Study week (± specified no. of days)
'D\WR
'D\
:HHN  
GD\V
:HHN
GD\V
:HHN  
GD\V
:HHN
GD\V
Early Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
Assessments
,QIRUPHG&RQVHQW
x
(OLJLELOLW\FULWHULD
x
x
'HPRJUDSK\
x
6PRNLQJVWDWXV
x
0HGLFDO)DPLO\ KLVWRU\ RI FRQVHQWHG VXEMHFWV
LQFOXGLQJ &9 5LVN IDFWRUV DQG H[DFHUEDWLRQ
KLVWRU\
x
3*[VDOLYDVDPSOH
x
3K\VLFDOH[DPLQDWLRQ
x
x
x
x
x
Safety Assessments
8ULQH3UHJQDQF\7HVW
x
x
x
x
([DFHUEDWLRQ$VVHVVPHQW
x
x
x
x
x
x
9LWDOVLJQV
x
x
x
x
x
6HULRXV $GYHUVH (YHQW DQG $GYHUVH 'UXJ
5HDFWLRQ$VVHVVPHQW
x
x
x
x
x
x
Efficacy Assessments
6SLURPHWU\7HVWLQJ3UHGRVHWURXJK)(9
x
x
x 
Subject Questionnaires 
$VWKPD&RQWURO7HVW
x
x
x
x
x
x
x
(4'
x
x
x
$VWKPD4XDOLW\RI
/LIH4XHVWLRQQDLUH
x
x
x
0$56$TXHVWLRQQDLUH
x
x
x
x



2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
46
Study Visits
Visit 1*
Screening#
Visit 2*
Randomisation
Visit 3
Phone call 1
Visit 4**
Visit 5
Phone call 2
Visit 6
Early Withdrawal
Study week (± specified no. of days)
'D\WR
'D\
:HHN  
GD\V
:HHN
GD\V
:HHN  
GD\V
:HHN
GD\V
Early Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH3$6$34
x
x
Inhaler correct use assessment
&ULWLFDODQGQRQFULWLFDOHUURUVUHFRUG
x
x
x
Medication Assessments
&RQFRPLWDQW0HGLFDWLRQ$VVHVVPHQW
x
x
x
x
x
'LVSHQVH6WXG\0HGLFDWLRQð
x
x
&ROOHFW6WXG\0HGLFDWLRQð
x
x
x
RAMOS/eCRF
5$0261*
x
x
x
x
x
H&5)
x
x
x
x
x
x
x

6$(DQG$'5PRQLWRULQJZLOORFFXUIURP'D\6$(UHODWHGWRVWXG\SDUWLFLSDWLRQVKRXOGEHJLQIURPVLJQLQJRI,&)$QDGGLWLRQDOVDIHW\DQG$&7FKHFNLVSURYLGHGE\SKRQHDW
ZHHNDQG

7KURXJKRXWWKHVWXG\WKHVWXG\PHGLFDWLRQZLOOEHGLVSHQVHGDQGFROOHFWHGE\WKHLQYHVWLJDWRUVLWH
3DWLHQWVWKDWIDLOVFUHHQLQJ PD\ EHUHVFUHHQHG RQO\XSRQDSSURYDOE\WKHPHGLFDOPRQLWRU
9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLVXVXDODVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH7KHQWKLVYLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEH
FROOHFWHGDWWKLVYLVLW:ULWWHQ,QIRUPHG&RQVHQWPXVWEHREWDLQHGSULRUWRLQLWLDWLRQRIVWXG\SURFHGXUHVRULQLWLDWLQJFKDQJHVLQPHGLFDWLRQV
 9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW 5DQGRPLVDWLRQYLVLW
3*[VDOLYDVDPSOHFROOHFWHGDW9LVLW5DQGRPLVDWLRQRUDQ\VFKHGXOHGFOLQLFYLVLWWKHUHDIWHU
2QO\LIHDUO\ZLWKGUDZDORFFXUVEHIRUH:HHN
2QO\IRUFKLOGEHDULQJZRPHQ
1RWH$OODGYHUVHHYHQWVZLOOEHUHFRUGHGLQWKHVRXUFHGRFXPHQWVEXWRQO\LQIRUPDWLRQUHJDUGLQJQRQVHULRXVDGYHUVHGUXJUHDFWLRQV$'5VDQGVHULRXVDGYHUVHHYHQWV6$(VZLOO
EHGRFXPHQWHGDQGUHSRUWHGLQWKHH&5)



2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
47

6FUHHQLQJDQG&ULWLFDO%DVHOLQH$VVHVVPHQWV
7KHIROORZLQJGHPRJUDSKLFSDUDPHWHUVZLOOEHFDSWXUHG\HDURIELUWKVH[DQGHWKQLFLW\
0HGLFDOPHGLFDWLRQIDPLO\KLVWRU\ZLOOEHDVVHVVHGDVUHODWHGWRWKHLQFOXVLRQH[FOXVLRQ
FULWHULDOLVWHGLQ6HFWLRQ DQGDVLQGLFDWHGLQWKHWLPHDQGHYHQWWDEOH
&DUGLRYDVFXODUPHGLFDOKLVWRU\&9ULVNIDFWRUVDQGH[DFHUEDWLRQKLVWRU\ZLOOEHDVVHVVHG
DVLQGLFDWHGLQWKHWLPHDQGHYHQWWDEOH
6PRNLQJVWDWXVZLOOEHDOVRFDSWXUHGDVIROORZVQRQVPRNHUFXUUHQWRUIRUPHUFLJDUHWWH
VPRNHUV)RUPHUVPRNHUVZLOOEHGHILQHGDVWKRVHZKRKDYHVWRSSHGVPRNLQJIRUDWOHDVW
PRQWKVSULRUWR9LVLWRU9LVLWLIWKHYLVLWDQGDUHFRPELQHG1XPEHURISDFN
\HDUVVKRXOGEHDVVHVVHG DWVFUHHQLQJ9LVLWQXPEHURISDFN\HDUV QXPEHURI
FLJDUHWWHVSHUGD\[QXPEHURI\HDUVVPRNHGHJFLJDUHWWHVSHUGD\IRU
\HDUVRUFLJDUHWWHVSHUGD\IRU\HDUV
3URFHGXUHVFRQGXFWHGDVSDUWRIWKH VXEMHFW¶VURXWLQHFOLQLFDOPDQDJHPHQW>HJEORRG
FRXQW@DQGREWDLQHGSULRUWRVLJQLQJRILQIRUPHGFRQVHQWPD\EHXWLOL]HGIRU6FUHHQLQJRU
EDVHOLQHSXUSRVHVSURYLGHGWKHSURFHGXUHPHHWVWKHSURWRFROGHILQHGFULWHULDDQGKDV
EHHQSHUIRUPHGLQWKHWLPHIUDPHRIWKHVWXG\
$&7ZLOOEHDVVHVVHGDWVFUHHQLQJ9LVLWDQGUDQGRPLVDWLRQ9LVLW$4/46(4
'DQG0$56$ZLOOEHDVVHVVHGDW9LVLW5DQGRPLVDWLRQ7KHVH3DWLHQW5HSRUWHG
2XWFRPHVTXHVWLRQQDLUHVVKRXOGEHFRPSOHWHGE\VXEMHFWVEHIRUHDQ\RWKHUDVVHVVPHQWDW
DFOLQLFLQYHVWLJDWRUVLWHYLVLWLQWKHRUGHUVSHFLILHG7KHFRUUHFWXVHRILQKDOHUZLOOEH
DVVHVVHGDOVRDWUDQGRPL]DWLRQYLVLW9LVLW

DIWHUUHDGLQJWKHSDFNDJHLQVHUWRISURGXFWE\WKHSDWLHQWDQG

DIWHUGHPRQVWUDWLRQRILWXVHE\WKH ,QYHVWLJDWRU$Q\FULWLFDOHUURUVZLOOEHUHJLVWHUHG
E\WKH,QYHVWLJDWRUZKHQXVLQJHDFKGHYLFH
%DVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\WKH,QYHVWLJDWRUXVLQJD
VSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHG KRXUV
EHIRUHEDVHOLQHVSLURPHWU\DQGXVXDODVWKPDPHGLFDWLRQZLOOEHQRWEHWDNHQE\WKH
SDWLHQWEHIRUHFRPLQJRQVLWH
1RVWXG\UHODWHGSURFHGXUHVPD\EHSHUIRUPHGXQWLOWKHLQIRUPHGFRQVHQWIRUP
GRFXPHQWKDVEHHQUHYLHZHGZLWKDQGVLJQHGE\WKHVXEMHFW

(IILFDF\
6HH6HFWLRQ IRUWKHHIILFDF\HQGSRLQWVDQG6HFWLRQ IRUWKHSURSRVHGWLPHDQGHYHQWV
WDEOH

,QKDOHU&RUUHFW8VH$VVHVVPHQW
&RUUHFWXVHRIWKHLQKDOHUZLOOEHDVVHVVHGDVRXWOLQHGLQWKH7LPHDQG(YHQWV7DEOH
6HFWLRQ

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
48
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUVIRU(OOLSWD
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURU
LVGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDO PHGLFDWLRQEHLQJ
LQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@1R
>@<HVLI\HVWLFNDSSURSULDWHRSWLRQVEHORZ
&ULWLFDO(UURUVIRU(OOLSWD
\HV
QR
1RQFULWLFDO
(UURUV
IRU
(OOLSWD
\HV
QR
)DLOHGWRRSHQFRYHU
1R
H[KDODWLRQ
EHIRUH
DQ
LQKDODWLRQ
6KRRN WKH GHYLFH XSVLGH GRZQ
DIWHUGRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUHZDV
QRW

ORQJ

VWHDG\

GHHS
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
1R VHDO E\ WKH OLSV DURXQG WKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWKROGEUHDWK
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
49
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUVIRU'LVNXV
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURU
LVGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJ
LQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@1R
>@<HVLI\HVWLFNDSSURSULDWHRSWLRQVEHORZ
&ULWLFDO(UURUVIRU'LVNXV
\HV
QR
1RQFULWLFDO(UURUVIRU
'LVNXV
\HV
QR
)DLOHGWRRSHQFRYHU
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
/HYHULVQRWSXVKHGEDFN
,QKDODWLRQPDQRHXYUHZDV
QRW

VWHDG\

GHHS
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
'LGQRWKROGEUHDWK
([KDOHGGLUHFWO\ LQWRPRXWKSLHFH
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
50
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUV IRU7XUEXKDOHU
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURU
LVGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJ
LQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@1R
>@<HVLI\HVWLFNDSSURSULDWHRSWLRQVEHORZ
&ULWLFDO(UURUVIRU7XUEXKDOHU
\HV
QR
1RQFULWLFDO(UURUVIRU
7XUEXKDOHU
\HV
QR
)DLOHGWRUHPRYHFDS
'HYLFHWLSSHGGRZQZDUGV
DIWHUGRVHSUHSDUDWLRQ
'LGQRWKROGGHYLFHXSULJKW
2.GXULQJGRVHSUHSDUDWLRQ
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
%DVHQRWWZLVWHGIXOO\EDFNZDUGV
DQGIRUZDUGVQRFOLFNKHDUG
,QKDODWLRQPDQRHXYUHZDV
QRW

IRUFHIXO

GHHS
1RWHWR+&3 LWLVLPSRUWDQW
WKDWWKHLQKDODWLRQLVIRUFHIXO
DQGGHHSIURPWKHVWDUWIRU
WKLVLQKDOHU
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWKROGEUHDWK
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@

7URXJKSUHGRVH)(9DVVHVVPHQW
)(9ZLOOEH PHDVXUHGWRDVVHVVOXQJIXQFWLRQDW9LVLW5DQGRPLVDWLRQDQG9LVLW
:HHNDVRXWOLQHGLQWKH7LPHDQG(YHQWV7DEOH9LVLW:HHNVKRXOGEH
VFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQYLVLW0HDVXUHPHQWVVKRXOG
EHWDNHQSUHGRVHDQGVXEMHFWVVKRXOGEHLQVWUXFWHGQRWWRWDNHWKHLUDVWKPD
PHGLFDWLRQVWXG\GUXJSULRUWRFRPLQJLQWRWKHFOLQLFDWWKHVHYLVLWV6XEMHFWVVKRXOGDOVR

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
51
ZLWKKROGIURPXVLQJWKHLUUHVFXHPHGLFDWLRQIRUDWOHDVWKRXUVSULRUWR9LVLW
5DQGRPLVDWLRQDQG 9LVLW:HHN
$OOVLWHVZLOOXVHVWDQGDUGLVHGVSLURPHWU\HTXLSPHQWSURYLGHGE\*6.)RUHDFK
REVHUYDWLRQDWOHDVWZLWKQRPRUHWKDQHIIRUWVZLOOEHREWDLQHG$WOHDVWWZRRIWKH
VSLURPHWU\HIIRUWVVKRXOGEHDFFHSWDEOHDQGUHSHDWDEOH7KHEHVW)(9YDOXHZLOOEH
UHFRUGHGLQWKHH&5)
7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRSHUIRUPWKHVSLURPHWU\DWWKHVDPH
WLPHRIWKHGD\DW9LVLWDQGDW9LVLW

4XHVWLRQQDLUHV

$VWKPD&RQWURO7HVW$&7
7KH$&7LVDYDOLGDWHGVHOIDGPLQLVWHUHGTXHVWLRQQDLUHXWLOLVLQJTXHVWLRQVWRDVVHVV
DVWKPDFRQWUROGXULQJWKHSDVWZHHNVRQDSRLQWFDWHJRULFDOVFDOHWR6XEMHFWV
ZLOOFRPSOHWHWKH$&7DW6FUHHQLQJ9LVLWDW5DQGRPLVDWLRQ9LVLWDW:HHN
3KRQH&DOORU9LVLWDW:HHN 9LVLWDW:HHN3KRQH&DOORU9LVLWDQG
DW:HHN9LVLW (DUO\:LWKGUDZDOYLVLW
$Q$&7VFRUHRIWRVXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLVXQOLNHO\WREHZHOO
FRQWUROOHG$VFRUHRIWRVXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLVOLNHO\WREHZHOO
FRQWUROOHG
3OHDVHUHIHUWR$SSHQGL[ DQGWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV

$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH$4/46
7KH$4/4LVDGLVHDVHVSHFLILFVHOIDGPLQLVWHUHGTXDOLW\RIOLIHTXHVWLRQQDLUHGHYHORSHG
WRHYDOXDWHWKHLPSDFWRIDVWKPDWUHDWPHQWVRQWKHTXDOLW\RIOLIHRIDVWKPDVXIIHUHUVRYHU
WKHODVWZHHNV>-XQLSHU @$4/46ZLOOEHPHDVXUHGDW5DQGRPLVDWLRQ9LVLW
DW:HHN 9LVLW(DUO\:LWKGUDZDOYLVLW 3OHDVHUHIHUWR$SSHQGL[ DQGWKH6WXG\
3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV

(XUR4RO4XHVWLRQQDLUH(4'/HYHO
*HQHUDOKHDOWKVWDWXVZLOOEHDVVHVVHGZLWKWKH(XUR4RO(4'/HYHO4XHVWLRQQDLUH
DW5DQGRPLVDWLRQ9LVLWDQGDW:HHN9LVLW(DUO\:LWKGUDZDOYLVLW
3OHDVHUHIHUWR$SSHQGL[ DQGWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV

0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$
6XEMHFW¶VVHOI UHSRUWHG DGKHUHQFHWRPHGLFDWLRQZLOOEHDVVHVVHGZLWKWKH0HGLFDWLRQ
$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDW9LVLW:HHN9LVLW
DQG:HHN9LVLW(DUO\:LWKGUDZDOYLVLW
7KH0$56$LVD LWHPTXHVWLRQQDLUHZKHUHPHGLFDWLRQXVHLVUDWHGRQDSRLQW
/LNHUWVFDOHLQGLFDWLQJµDOZD\V¶WRLQGLFDWLQJµQHYHU¶,WKDVEHHQYDOLGDWHGDVDVHOI

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
52
UHSRUWHGPHDVXUHRIDGKHUHQFHZLWK,&6IRUVXEMHFWVZLWKDVWKPDDQGLQFOXGHVJHQHULF³,
XVHLWUHJXODUO\HYHU\GD\´DQGOXQJFRQGLWLRQVSHFLILFTXHVWLRQVDERXWPHGLFDWLRQXVH
³,RQO\XVHLWZKHQ,IHHOEUHDWKOHVV´>&RKHQ@7KHUHLVQRVSHFLILHGWLPHIUDPHRQ
ZKLFKUHVSRQVHVVKRXOGEHEDVHG
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH0$56$DWWKHVDPHWLPHDW
WKHVSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH0$56$KDYHQRVSHFLILHG
WLPHIUDPHRQZKLFKUHVSRQVHVVKRXOGEHEDVHG

3DWLHQWV6DWLVIDFWLRQDQG3UHIHUHQFHZLWKWKHGHYLFH3$6$3
4XHVWLRQQDLUH
7KH3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH3$6$34>.R]PD@LVD
PXOWLLWHPPHDVXUHRIUHVSLUDWRU\LQKDODWLRQGHYLFHVDWLVIDFWLRQDQGSUHIHUHQFHGHVLJQHG
WREHHDVLO\XQGHUVWRRGDQGDGPLQLVWHUHGWRSDWLHQWVZLWKDVWKPDDQG&23'3DWLHQW
VDWLVIDFWLRQZLWKHDFKGHYLFHDQGGHYLFHSUHIHUHQFHZLOOEHDVVHVVHGDW:HHN9LVLW
(DUO\:LWKGUDZDOYLVLWLIVXEMHFWLVZLWKGUDZQEHIRUH:HHN9LVLW
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH3$6$34DWWKHVDPHWLPHDW
WKHVSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH3$6$34KDVQRVSHFLILHG
WLPHIUDPHRQZKLFKUHVSRQVHVVKRXOGEHEDVHG

6DIHW\
3ODQQHGWLPHSRLQWVIRUDOOVDIHW\DVVHVVPHQWVDUHOLVWHGLQWKH7LPHDQG(YHQWV7DEOH
VHH6HFWLRQ
6HULRXV$GYHUVH(YHQWV6$(DQGQRQVHULRXV$GYHUVH'UXJ5HDFWLRQV$'5 ZLOOEH
FROOHFWHGLQWKLVVWXG\
6DIHW\HQGSRLQWVZLOOLQFOXGH
!
)UHTXHQF\DQGW\SHRIVHULRXVDGYHUVHHYHQWV
!
)UHTXHQF\DQGW\SHRIQRQVHULRXVDGYHUVHGUXJUHDFWLRQVUHODWHGWRWUHDWPHQW

$GYHUVH(YHQWV$($GYHUVH'UXJ5HDFWLRQV$'5VDQG
6HULRXV$GYHUVH(YHQWV6$(V
7KHGHILQLWLRQVRIDQ$($'5RU6$(FDQEHIRXQGLQ$SSHQGL[
7KH,QYHVWLJDWRUDQGWKHLUGHVLJQHHVDUHUHVSRQVLEOHIRUGHWHFWLQJGRFXPHQWLQJDQG
UHSRUWLQJHYHQWVWKDWPHHWWKHGHILQLWLRQRIDQ$(RU6$($OODGYHUVHHYHQWVZLOOEH
UHFRUGHGLQWKHVRXUFHGRFXPHQWVEXWRQO\LQIRUPDWLRQUHJDUGLQJ QRQVHULRXVDGYHUVH
GUXJUHDFWLRQV$'5VDQGVHULRXVDGYHUVHHYHQWV6$(VZLOOEHGRFXPHQWHGDQG
UHSRUWHGLQWKHH&5)

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
53

7LPHSHULRGDQG)UHTXHQF\IRUFROOHFWLQJQRQVHULRXV$'5VDQG6$(
LQIRUPDWLRQ
!
$OOQRQVHULRXV$'5VDQG6$(VZLOOEHFROOHFWHGIURPWKH VWDUWRI6WXG\
7UHDWPHQWXQWLOWKHHQGRIWKHVWXG\VHH6HFWLRQDWWKHWLPHSRLQWV
VSHFLILHGLQWKH7LPHDQG(YHQWV7DEOH6HFWLRQ
!
0HGLFDORFFXUUHQFHVWKDWEHJLQSULRUWRWKHVWDUWRIVWXG\WUHDWPHQWEXWDIWHU
REWDLQLQJLQIRUPHGFRQVHQWPD\EHUHFRUGHGRQWKH0HGLFDO+LVWRU\&XUUHQW
0HGLFDO&RQGLWLRQVVHFWLRQRIWKH&5)
!
$Q\6$(VDVVHVVHGDVUHODWHGWRVWXG\SDUWLFLSDWLRQHJSURWRFROPDQGDWHG
SURFHGXUHVLQYDVLYHWHVWVRUFKDQJHLQH[LVWLQJWKHUDS\RUUHODWHGWRD*6.
SURGXFWZLOOEHUHFRUGHGIURPWKHWLPHDVXEMHFWFRQVHQWVWRSDUWLFLSDWHLQWKH
VWXG\XSWRDQGLQFOXGLQJDQ\IROORZXSFRQWDFW
!
$OO6$(VZLOOEHUHFRUGHGDQGUHSRUWHGWR*6.ZLWKLQ KRXUVDVLQGLFDWHGLQ
$SSHQGL[
!
,QYHVWLJDWRUVDUHQRWREOLJDWHGWRDFWLYHO\VHHN$(VRU6$(VLQIRUPHUVWXG\
VXEMHFWV+RZHYHULIWKHLQYHVWLJDWRUOHDUQVRIDQ\6$(LQFOXGLQJDGHDWKDWDQ\
WLPHDIWHUDVXEMHFWKDVEHHQGLVFKDUJHGIURPWKHVWXG\DQGKHVKHFRQVLGHUVWKH
HYHQWUHDVRQDEO\UHODWHGWRWKHVWXG\WUHDWPHQWRUVWXG\SDUWLFLSDWLRQWKH
LQYHVWLJDWRUPXVWSURPSWO\QRWLI\*6.
127(7KHPHWKRGRIUHFRUGLQJHYDOXDWLQJDQGDVVHVVLQJFDXVDOLW\RI$(VDQG6$(V
SOXVSURFHGXUHVIRUFRPSOHWLQJDQGWUDQVPLWWLQJ6$(UHSRUWVWR*6.DUHSURYLGHGLQ
$SSHQGL[

0HWKRGRI'HWHFWLQJQRQVHULRXV$'5VDQG6$(V
7KH,QYHVWLJDWRURUVLWHVWDIIZLOOEHUHVSRQVLEOHIRUGHWHFWLQJGRFXPHQWLQJDQGUHSRUWLQJ
HYHQWVWKDWPHHWWKHGHILQLWLRQRIDQRQVHULRXVDGYHUVHGUXJUHDFWLRQ$'5RUVHULRXV
DGYHUVHHYHQWV6$(
7KHPHWKRGRIGHWHFWLQJUHFRUGLQJHYDOXDWLQJDQGIROORZXSRI6$(VDQGQRQVHULRXV
$'5VSOXVSURFHGXUHVIRUFRPSOHWLQJDQGWUDQVPLWWLQJ6$(UHSRUWVWR*6.DUHSURYLGHG
LQWKH6503URFHGXUHVIRUSRVWVWXG\6$(VQRQVHULRXV$'5VDUHSURYLGHGLQWKH650
&DUHZLOOEHWDNHQQRWWRLQWURGXFHELDVZKHQGHWHFWLQJ$(VDQGRU6$(V2SHQHQGHG
DQGQRQOHDGLQJYHUEDOTXHVWLRQLQJRIWKHVXEMHFWLVWKHSUHIHUUHGPHWKRGWRLQTXLUHDERXW
$(RFFXUUHQFH$SSURSULDWHTXHVWLRQVLQFOXGH
!
³+RZ DUH \RX IHHOLQJ"´ ³+DYH \RX KDG DQ\ RWKHU PHGLFDO SUREOHPV
VLQFH\RXUODVWYLVLWFRQWDFW"´³+DYH\RXWDNHQDQ\QHZPHGLFLQHVRWKHU
WKDQWKRVHSURYLGHGLQ WKLVVWXG\VLQFH\RXUODVWYLVLWFRQWDFW"´
3RWHQWLDO6$(VDQGQRQVHULRXV$'5VPD\EHLGHQWLILHGE\KRVSLWDOLVDWLRQDOHUWVWKURXJK
WKHPHGLFDOUHFRUG7KH,QYHVWLJDWRUZLOOKDYHWKHXOWLPDWHUHVSRQVLELOLW\IRUGHWHUPLQLQJ
FDXVDOLW\DQGVHULRXVQHVV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
54

)ROORZXSRIQRQVHULRXV$'5VDQG6$(V
$IWHUWKHLQLWLDOQRQVHULRXV$'5V6$(UHSRUWWKHLQYHVWLJDWRULVUHTXLUHGWRSURDFWLYHO\
IROORZHDFKVXEMHFWDWVXEVHTXHQWYLVLWVFRQWDFWV$OO6$(VDQGQRQVHULRXV$'5VZLOO
EHIROORZHGXQWLOUHVROXWLRQXQWLOWKHFRQGLWLRQVWDELOL]HVXQWLOWKHHYHQWLVRWKHUZLVH
H[SODLQHGRUXQWLOWKHVXEMHFWLVORVWWRIROORZXSDVGHILQHGLQ6HFWLRQ)XUWKHU
LQIRUPDWLRQRQIROORZXSSURFHGXUHVLVJLYHQLQ$SSHQGL[

&DUGLRYDVFXODUDQG'HDWK(YHQWV
)RUDQ\FDUGLRYDVFXODUHYHQWVGHWDLOHGLQ$SSHQGL[ DQGDOOGHDWKVZKHWKHURUQRWWKH\
DUHFRQVLGHUHG6$(VVSHFLILF&DUGLRYDVFXODU&9DQG'HDWKVHFWLRQVRI WKH&5)ZLOO
EHUHTXLUHGWREHFRPSOHWHG 7KHVHVHFWLRQVLQFOXGHTXHVWLRQVUHJDUGLQJFDUGLRYDVFXODU
LQFOXGLQJVXGGHQFDUGLDFGHDWKDQGQRQFDUGLRYDVFXODUGHDWK
7KH&9&5)VDUHSUHVHQWHGDVTXHULHVLQUHVSRQVHWRUHSRUWLQJRIFHUWDLQ&90HG'5$
WHUPV 7KH&9LQIRUPDWLRQVKRXOGEHUHFRUGHGLQWKHVSHFLILFFDUGLRYDVFXODUVHFWLRQRI
WKH&5)ZLWKLQRQHZHHNRIUHFHLSWRID&9(YHQWGDWDTXHU\SURPSWLQJLWVFRPSOHWLRQ
7KH'HDWK&5)LVSURYLGHGLPPHGLDWHO\DIWHUWKHRFFXUUHQFHRURXWFRPHRIGHDWKLV
UHSRUWHG,QLWLDODQGIROORZXSUHSRUWVUHJDUGLQJGHDWKPXVWEHFRPSOHWHGZLWKLQ RQH
ZHHNRIZKHQWKHGHDWKLVUHSRUWHG

'LVHDVH5HODWHG(YHQWVDQGRU'LVHDVH5HODWHG2XWFRPHV1RW
4XDOLI\LQJDV6$(V
$Q\FOLQLFDOO\VLJQLILFDQWVDIHW\DVVHVVPHQWVWKDWDUHDVVRFLDWHGZLWKWKHXQGHUO\LQJ
GLVHDVHXQOHVVMXGJHGE\WKH,QYHVWLJDWRUWREHPRUHVHYHUHWKDQH[SHFWHGIRUWKH
VXEMHFW¶VFRQGLWLRQDUHQRW WREHUHSRUWHGDVQRQVHULRXV$'5VRU6$(V

5HJXODWRU\5HSRUWLQJ5HTXLUHPHQWVIRU6$(V
3URPSWQRWLILFDWLRQRI6$(VE\WKH,QYHVWLJDWRUWR*6.LVHVVHQWLDOVRWKDWOHJDO
REOLJDWLRQVDQGHWKLFDOUHVSRQVLELOLWLHVWRZDUGVWKHVDIHW\RIVXEMHFWVDQGWKHVDIHW\RID
SURGXFWXQGHUFOLQLFDOLQYHVWLJDWLRQDUHPHW7KLVZLOODOVRLQFOXGHSRWHQWLDO6$(V
LGHQWLILHGE\KRVSLWDOLVDWLRQDOHUWVWKURXJKWKHPHGLFDOUHFRUG
*6.KDVDOHJDOUHVSRQVLELOLW\WRQRWLI\ERWKWKHORFDOUHJXODWRU\DXWKRULW\DQGRWKHU
UHJXODWRU\DJHQFLHVDERXWWKHVDIHW\RIDSURGXFWXQGHUFOLQLFDOLQYHVWLJDWLRQ*6.ZLOO
FRPSO\ZLWKFRXQWU\VSHFLILFUHJXODWRU\UHTXLUHPHQWVUHODWLQJWRVDIHW\UHSRUWLQJWRWKH
UHJXODWRU\DXWKRULW\,QGHSHQGHQW(WKLFV&RPPLWWHH,(&DQG,QYHVWLJDWRUV
,QYHVWLJDWRUVDIHW\UHSRUWVDUHSUHSDUHGIRUVXVSHFWHGXQH[SHFWHGVHULRXVDGYHUVH
UHDFWLRQVDFFRUGLQJWRORFDOUHJXODWRU\UHTXLUHPHQWVDQG*6.SROLF\DQGDUHIRUZDUGHG
WRLQYHVWLJDWRUVDVQHFHVVDU\
$Q,QYHVWLJDWRUZKRUHFHLYHVDQLQYHVWLJDWRUVDIHW\UHSRUWGHVFULELQJD6$(VRURWKHU
VSHFLILFVDIHW\LQIRUPDWLRQHJVXPPDU\RUOLVWLQJRI6$(VIURP*6.ZLOOILOHLWZLWK
WKH,%DQGZLOOQRWLI\WKH,(&LIDSSURSULDWHDFFRUGLQJWRORFDOUHTXLUHPHQWV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
55
7KHPHWKRGRIGHWHFWLQJUHFRUGLQJHYDOXDWLQJDQGIROORZXSRI6$(VDQGQRQVHULRXV
$'5VSOXVSURFHGXUHVIRUFRPSOHWLQJDQGWUDQVPLWWLQJ6$(UHSRUWVWR*6.DUHSURYLGHG
LQWKH6503URFHGXUHVIRUSRVWVWXG\6$(VQRQVHULRXV$'5VDUHSURYLGHGLQWKH650
3URFHGXUHVIRUGRFXPHQWLQJWUDQVPLWWLQJDQGIROORZXSRIPHGLFDOGHYLFHLQFLGHQWV
DORQJZLWKWKHUHJXODWRU\UHSRUWLQJUHTXLUHPHQWVIRUPHGLFDOGHYLFHVDUHSURYLGHGLQWKH
650

3UHJQDQF\
!
'HWDLOVRIDOOSUHJQDQFLHVLQIHPDOHVXEMHFWVZLOOEHFROOHFWHGIURPWKHWLPHWKH
LQIRUPHGFRQVHQWLVVLJQHG9LVLWDQGXQWLOWKHHQGRIWKHVWXG\9LVLW
!
$Q\SUHJQDQF\WKDWRFFXUVGXULQJVWXG\SDUWLFLSDWLRQPXVWEHUHSRUWHGXVLQJD
FOLQLFDOWULDOSUHJQDQF\IRUP
!
,IDSUHJQDQF\LVUHSRUWHGWKHQWKHLQYHVWLJDWRUVKRXOGLQIRUP*6.ZLWKLQ
ZHHNVRIOHDUQLQJRIWKHSUHJQDQF\DQGVKRXOGIROORZWKHSURFHGXUHVRXWOLQHGLQ
$SSHQGL[
!
$Q\6$(RFFXUULQJLQDVVRFLDWLRQZLWKDSUHJQDQF\EURXJKWWRWKH
LQYHVWLJDWRU¶VDWWHQWLRQDIWHUWKHVXEMHFWKDVFRPSOHWHGWKHVWXG\DQGFRQVLGHUHG
E\WKHLQYHVWLJDWRUDVSRVVLEO\UHODWHGWRWKHVWXG\WUHDWPHQWPXVWEHSURPSWO\
UHSRUWHGWR*6.

0HGLFDO'HYLFH,QFLGHQWV,QFOXGLQJ0DOIXQFWLRQV
0HGLFDOGHYLFHVVSLURPHWHUVZLOOEHSURYLGHGE\*6.IRUXVHLQWKLVVWXG\ +RZHYHU
QRQHRIWKHGHYLFHVSURYLGHGDUHPDQXIDFWXUHGE\RURQEHKDOIRI*6.

3K\VLFDO([DPV
$FRPSOHWHSK\VLFDOH[DPLQDWLRQZLOOLQFOXGHDWDPLQLPXPDVVHVVPHQWRIWKH
&DUGLRYDVFXODU5HVSLUDWRU\*DVWURLQWHVWLQDODQG1HXURORJLFDOV\VWHPV
,QYHVWLJDWRUVVKRXOGSD\VSHFLDODWWHQWLRQWRFOLQLFDOVLJQVUHODWHGWRSUHYLRXVVHULRXV
LOOQHVVHV

9LWDO6LJQV
9LWDOVLJQPHDVXUHPHQWVZLOOLQFOXGHKHLJKWZHLJKWSXOVHUDWHV\VWROLFDQGGLDVWROLF
EORRGSUHVVXUH
9LWDOVLJQVZLOOEHPHDVXUHGDQGUHFRUGHGLQWKHH&5)DW6FUHHQLQJYLVLW9LVLWDWWKH
5DQGRPLVDWLRQ9LVLW'D\DW:HHN9LVLWDW:HHN9LVLWDQGDW(DUO\
:LWKGUDZDO9LVLWH[FHSWIRUKHLJKWDQGZHLJKWWKDWZLOOEHFROOHFWHGDW9LVLWRQO\

(OHFWURFDUGLRJUDP(&*
$Q(&*LVQRWUHTXLUHGSULRUWRHQWHULQJWKLVVWXG\7KHUHDUHQRRWKHUUHJXODU(&*V
UHTXLUHGE\WKLVSURWRFRO

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
56

&OLQLFDO6DIHW\/DERUDWRU\$VVHVVPHQWV
7KHUHDUHQRFOLQLFDOVDIHW\ODERUDWRU\DVVHVVPHQWUHTXLUHPHQWVIRUWKLVVWXG\
$Q\DEQRUPDOODERUDWRU\WHVWUHVXOWVKHPDWRORJ\FOLQLFDOFKHPLVWU\RUXULQDO\VLVRU
RWKHUVDIHW\DVVHVVPHQWVHJ(&*VUDGLRORJLFDOVFDQVYLWDOVLJQVPHDVXUHPHQWV
UHFRUGHGGXULQJDURXWLQHFOLQLFYLVLWLQFOXGLQJWKRVH WKDWZRUVHQIURPEDVHOLQHDQGIHOW
WREHFOLQLFDOO\VLJQLILFDQWLQWKHPHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKH,QYHVWLJDWRUDUH
WREHUHFRUGHGDVQRQVHULRXV$'5VRU6$(VDVDSSURSULDWH

*HQHWLFV
,QIRUPDWLRQUHJDUGLQJJHQHWLFUHVHDUFKLVLQFOXGHGLQ$SSHQGL[

'$7$0$1$*(0(17
!
)RUWKLVVWXG\VXEMHFWGDWDZLOOEHHQWHUHGLQWR*6.GHILQHG&5)VWUDQVPLWWHG
HOHFWURQLFDOO\WR*6.RUGHVLJQHHDQGFRPELQHGZLWKGDWDSURYLGHGIURPRWKHU
VRXUFHVLQDYDOLGDWHGGDWDV\VWHP
!
0DQDJHPHQWRIFOLQLFDOGDWDZLOOEHSHUIRUPHGLQDFFRUGDQFHZLWKDSSOLFDEOH*6.
VWDQGDUGVDQGGDWDFOHDQLQJSURFHGXUHVWRHQVXUHWKHLQWHJULW\RIWKHGDWDHJ
UHPRYLQJHUURUVDQGLQFRQVLVWHQFLHVLQWKHGDWD
!
$GYHUVHHYHQWVDQGFRQFRPLWDQWPHGLFDWLRQVWHUPVZLOOEHFRGHGXVLQJ0HG'5$
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHVDQGDQLQWHUQDOYDOLGDWHGPHGLFDWLRQ
GLFWLRQDU\*6.'UXJ
!
&5)VLQFOXGLQJTXHULHVDQGDXGLWWUDLOVZLOOEHUHWDLQHGE\*6.DQGFRSLHVZLOO
EHVHQWWRWKHLQYHVWLJDWRUWRPDLQWDLQDVWKHLQYHVWLJDWRUFRS\6XEMHFWLQLWLDOVZLOO
QRWEHFROOHFWHGRUWUDQVPLWWHGWR*6.DFFRUGLQJWR*6.SROLF\

67$7,67,&$/&216,'(5$7,216$1''$7$
$1$/<6(6

+\SRWKHVHV
7KHREMHFWLYHRIWKHVWXG\LVWRFRPSDUHWKHHIILFDF\RIIOXWLFDVRQHIXURDWH))YLODQWHURO
9,,QKDODWLRQ3RZGHU))9,PFJPFJRU))9,PFJPFJZLWKXVXDO
,&6/$%$LQKDODWLRQGU\SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\RYHUVL[PRQWKVLQD
ODUJHSRSXODWLRQRIVXEMHFWVZLWKDVWKPD
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQHLQWKH$&7WRWDOVFRUH
DVVHVVHGDW:HHN9LVLW5HJDUGLQJWKHSULPDU\HIILFDF\HQGSRLQWLHWKHFKDQJH
IURPEDVHOLQHLQWKH$&7WRWDOVFRUHDVVHVVHGDW:HHN>9LVLW@WKHSULPDU\DQDO\VLV
ZLOOVKRZWKDWWKHIL[HGFRPELQDWLRQ ))9,PFJPFJRUPFJPFJLVQRQ
LQIHULRUWRDQ\RWKHU,&6/$%$FRPELQDWLRQVLQLQKDODWLRQSRZGHUDVVXPLQJDQRQ
LQIHULRULW\PDUJLQRI1RQLQIHULRULW\ZLOOEHFODLPHGLIWKHWZRVLGHGFRQILGHQFH
LQWHUYDORQWKHGLIIHUHQFHLQPHDQSULPDU\HIILFDF\HQGSRLQWV))9,PLQXV&RPSDUDWRU
SUHFOXGHVWKHQRQLQIHULRULW\PDUJLQRI

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
57
,IDQGRQO\LIQRQLQIHULRULW\LVVLJQLILFDQWO\DFKLHYHGDW:HHN9LVLWZLWKUHJDUG
WRWKHSULPDU\HQGSRLQWWKHQQRQLQIHULRULW\RIWKHIL[HGFRPELQDWLRQ))9,
PFJPFJRUPFJPFJWRDQ\RWKHU,&6/$%$FRPELQDWLRQVZLOOEHWHVWHGDW
:HHN9LVLWFRQVLGHULQJWKHVDPHQRQLQIHULRULW\PDUJLQRI1RQLQIHULRULW\
ZLOOEHFODLPHGLIWKHWZRVLGHGFRQILGHQFHLQWHUYDORQWKHGLIIHUHQFHLQPHDQ
SULPDU\HIILFDF\HQGSRLQWV))9,PLQXV&RPSDUDWRUDW:HHN9LVLWSUHFOXGHVWKH
QRQLQIHULRULW\PDUJLQRI
2IQRWHDVWKHWZRWHVWVIRUQRQLQIHULRULW\DUHVHTXHQWLDOO\SHUIRUPHGWKHFORVXUH
SULQFLSOHKROGVDQGWKHUHLVQRQHHGWRDGMXVWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
LHIRUHDFKWHVW

6DPSOH6L]H&RQVLGHUDWLRQV

6DPSOH6L]H$VVXPSWLRQV
5HVXOWVEDVHGRQWKH+=$VWXG\KDYHVKRZQWKDWWKHHVWLPDWHGVWDQGDUGGHYLDWLRQ
RIWKHFKDQJHLQ$&7VFRUHZDV8QSXEOLVKHG GDWDKDYHVKRZQWKDWWKHVWDQGDUG
GHYLDWLRQRIFKDQJHRI$&7UDQJHGIURPWR7KHUHIRUHDVRPHZKDWFRQVHUYDWLYH
FKRLFHRI6'RISRLQWLVUHWDLQHG
%DVHGRQWKHOLWHUDWXUH>6FKDW]@WKH0LQLPDOO\,PSRUWDQW'LIIHUHQFH0,'RIWKH
$&7FRXOGEHFRQVLGHUHGDVSRLQWV+DOIWKLV0,'LHFRXOGWKHUHIRUHEHXVHGWR
GHILQHWKHQRQLQIHULRULW\PDUJLQ
$VVXPLQJDSRLQWVWDQGDUGGHYLDWLRQIRUWKHFKDQJHLQ$&7WRWDOVFRUHDW:HHN
9LVLWDSRLQWQRQLQIHULRULW\PDUJLQDQGDWZRVLGHGQRPLQDOVLJQLILFDQFHOHYHO
RIWKHVDPSOHVL]HQHHGHGSHUJURXSWRDFKLHYHDWOHDVWDSRZHULVLHD
WRWDORIVXEMHFWV$VVXPLQJDGURSRXWUDWHDURXQGVXEMHFWVPXVWEH
UDQGRPL]HGHLWKHUWR))9,RUWRWKHDOWHUQDWLYH,&6/$%$LQUDWLRWRDFKLHYHDWOHDVW
DSRZHU

6DPSOH6L]H6HQVLWLYLW\
7RGHPRQVWUDWHWKHVHQVLWLYLW\RIWKHVDPSOHVL]HFDOFXODWLRQIRUWKLVVWXG\WKHIROORZLQJ
WDEOHSUHVHQWVWKHSRZHURIWKHVWXG\XQGHUGLIIHUHQWFLUFXPVWDQFHVLQWHUPVRIWKH
VWDQGDUGGHYLDWLRQ
7KHDVVXPSWLRQXVHGLVVKDGHG
6WDQGDUGGHYLDWLRQ
3RZHUIRUWKHVXEMHFWVHYDOXDEOH
1 











2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
58

6DPSOH6L]H5HHVWLPDWLRQRU$GMXVWPHQW
1RWSODQQHG

'DWD$QDO\VLV&RQVLGHUDWLRQV

$QDO\VLV3RSXODWLRQV
3RSXODWLRQVFRQVLGHUHGIRUDQDO\VLVDUHDVIROORZV
,QWHQWWRWUHDW,77SRSXODWLRQ$OOUDQGRPL]HGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQH
GRVHRIWKHSUHVFULSWLRQRIVWXG\PHGLFDWLRQ HLWKHU))9,RU XVXDO,&6/$%$DVWKPD
PDLQWHQDQFHWKHUDS\7KH,77SRSXODWLRQ ZLOOEHXVHGWRDQDO\]HWKHSULPDU\HIILFDF\
HQGSRLQWDQDO\VLVWKHVHFRQGDU\HIILFDF\HQGSRLQWDQGRWKHUHIILFDF\HQGSRLQWV6XEMHFWV
ZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVUDQGRPL]HGIRU WKH,77SRSXODWLRQ
3HUSURWRFRO33SRSXODWLRQ ,77VXEMHFWVZLWKRXWDQ\SURWRFROGHYLDWLRQVVSHFLILFDOO\
GHILQHGLQWKH5$33URWRFROGHYLDWLRQVZLOOEHUHYLHZHGDQGZLOOEHFODVVLILHGDV
LPSRUWDQWRUQRWLPSRUWDQWGXULQJGDWDUHYLHZPHHWLQJV WKDWZLOOEHKHOGEHIRUHGDWDEDVH
ORFN'HYLDWLRQV FODVVLILHGDVLPSRUWDQW ZLOOEHIXUWKHUGHILQHGDFFRUGLQJWRZKHWKHUWKH\
UHTXLUHWKHSDWLHQWWREHH[FOXGHGIURPWKH33SRSXODWLRQ'HYLDWLRQVWKDWZRXOGH[FOXGH
DSDWLHQWIURPWKH33SRSXODWLRQZLOOEHGHILQHGLQWKH5$3 6DIHW\SRSXODWLRQ $OO
HQUROOHGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQHGRVHRIWKHSUHVFULSWLRQRIVWXG\PHGLFDWLRQ
HLWKHU))9,RUXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\DQGFRQVLGHUHGDV
WUHDWHG7KH6DIHW\SRSXODWLRQ ZLOOEHWKHEDVLVIRUVDIHW\DQDO\VHV6XEMHFWVZLOOEH
DVVLJQHGWRWKHWUHDWPHQWJURXSDVWUHDWHGIRUWKH6DIHW\SRSXODWLRQ
'HWDLOVRIWKHDQDO\VLVGDWDVHWVWREHFUHDWHGZLOOEHVSHFLILHGLQWKH5HSRUW$QDO\VLV3ODQ
5$3

,QWHULP$QDO\VLV
1RWDSSOLFDEOH

.H\(OHPHQWVRI $QDO\VLV3ODQ
7KHSULPDU\FRPSDULVRQRILQWHUHVWLVWKHFRPSDULVRQRIWKHFKDQJHIURPEDVHOLQH9LVLW
LQWKHWRWDO$&7VFRUHDVVHVVHGDW:HHN9LVLWEHWZHHQ))9,PFJPFJRU
PFJPFJDQGXVXDO,&6/$%$LQKDODWLRQSRZGHUIRUDVWKPDPDLQWHQDQFH
WKHUDS\
7KHSULPDU\VHWIRUDQDO\VLVZLOOEHSHUIRUPHGRQWKHLQWHQWWRWUHDWSRSXODWLRQ$
VHQVLWLYLW\DQDO\VLVZLOOEHSHUIRUPHGLQWKH33SRSXODWLRQ
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHVLGHGQRPLQDOOHYHO
RIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,WR
,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
59
,IDQGRQO\LIQRQLQIHULRULW\LVDFKLHYHGIRUWKHSULPDU\HQGSRLQWDW:HHN9LVLW
WKHQWKHNH\VHFRQGDU\HQGSRLQWLHWKHFKDQJHIURPEDVHOLQHLQWKHWRWDO$&7VFRUH
DVVHVVHGDW:HHN9LVLWZLOOEHWHVWHG$W:HHN9LVLWQRQLQIHULRULW\RI
))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORI
VLJQLILFDQFH,I1RQLQIHULRULW\LVDFKLHYHGWKHQVXSHULRULW\RI))9,WR,&6/$%$ZLOO
VWLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
2IQRWHWKLVVWHSGRZQWHVWLQJSURFHGXUHVWLOOVWURQJO\FRQWUROVWKHRYHUDOOW\SH,HUURUDW
WKHWZRVLGHGOHYHO
'HILQLWLRQRIWKHWUHDWPHQWIDLOXUHZLOOEHDVIROORZ
!
7UHDWPHQWZLWKGUDZDO
!
&KDQJHRIWUHDWPHQW
!
'RVHLQFUHDVHEH\RQGWKHPD[LPXPDOORZHGGDLO\GRVHLQWKH(8OLFHQVHIRU
))9,!PFJPFJIRU)36!PFJWZLFHGDLO\IRU%8') !PFJ
WZLFHGDLO\
2WKHU&RPSDULVRQVRI,QWHUHVW2WKHUHIILFDF\HQGSRLQWVDQGVDIHW\HQGSRLQWVZLOOEH
GHVFULEHG(VWLPDWHGGLIIHUHQFHVEHWZHHQJURXSVZLWKFRQILGHQFHLQWHUYDOVZLOOEH
SURYLGHGZKHQDSSOLFDEOH
'DWDZLOOEHOLVWHGDQGVXPPDUL]HG DFFRUGLQJWRWKH*6.UHSRUWLQJVWDQGDUGVZKHUH
DSSOLFDEOH&RPSOHWHGHWDLOVZLOOEHGRFXPHQWHGLQWKH5HSRUWLQJ$QDO\VLV3ODQ5$3
$Q\GHYLDWLRQVIURPRUDGGLWLRQVWRWKHRULJLQDODQDO\VLVSODQGHVFULEHGLQWKLVSURWRFRO
ZLOOEHGRFXPHQWHGLQWKH5$3DQGILQDOVWXG\UHSRUW'HVFULSWLYHVXPPDULHVZLOOEH
SURYLGHGE\WUHDWPHQWJURXS
'HPRJUDSKLFDQGEDVHOLQHFKDUDFWHULVWLFVZLOOEHVXPPDUL]HG
&RQWLQXRXVYDULDEOHV ZLOOEHVXPPDUL]HGXVLQJGHVFULSWLYHVWDWLVWLFVQXPEHURIREVHUYHG
DQGPLVVLQJGDWDPHDQVWDQGDUGGHYLDWLRQ6'PHGLDQ44PLQLPXPDQG
PD[LPXP
&DWHJRULFDOYDULDEOHV ZLOOEHVXPPDUL]HGDVQXPEHUVRIREVHUYHGDQGPLVVLQJGDWD
FRXQWVDQGSHUFHQWDJHIRUHDFKFDWHJRU\UHSRUWHGWRWKHQXPEHURIQRQPLVVLQJYDOXHV
)RUELQDU\YDULDEOHVFRQILGHQFHLQWHUYDOVIRUSURSRUWLRQVZLOOEHHVWLPDWHGEDVHGRQ
WKH&ORSSHU3HDUVRQPHWKRG
7KHFRQWUDVWEHWZHHQ))9,DQGXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\LQ
LQKDODWLRQSRZGHUZLOOEHRISULPDU\LQWHUHVWIRUDOOHIILFDF\HQGSRLQWV
1RQLQIHULRULW\RI))9,YHUVXVXVXDO,&6/$%$DVWKPDWKHUDS\ZLOOEHILUVWWHVWHGDW
:HHN9LVLW,IDQGRQO\LIVLJQLILFDQFHLVDFKLHYHGDW:HHN9LVLWWKHQQRQ
LQIHULRULW\ZLOOEHWHVWHGDW:HHN9LVLWDWWKHWZRVLGHGOHYHORIVLJQLILFDQFH
7KLVVWHSGRZQWHVWLQJSURFHGXUHVWURQJO\FRQWUROVWKHRYHUDOOW\SH,HUURUDWWKH
WZRVLGHGOHYHO

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
60
,IQRQLQIHULRULW\LVDFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI))9,YHUVXVXVXDO
,&6/$%$DVWKPDWKHUDS\ZLOOEHWHVWHGDWWKHVDPH WZRVLGHGQRPLQDOVLJQLILFDQFH
OHYHORI ,IQRQLQIHULRULW\LVDFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI
))9,YHUVXVXVXDO,&6/$%$DVWKPDWKHUDS\ZLOOEHWHVWHGDWWKHVDPHWZRVLGHG
QRPLQDOVLJQLILFDQFHOHYHORI
%DVHOLQH$&7VFRUHZLOOEHLQFOXGHGLQWKHSULPDU\HIILFDF\DQDO\VHV*HQGHUDJHVWXG\
VLWHDQGSRWHQWLDOO\VHDVRQDWUDQGRPL]DWLRQ ZLOOEHIXUWKHULQYHVWLJDWHGLQVHQVLWLYLW\
DQDO\VHVZKHQDSSURSULDWH2WKHUFRYDULDWHVPD\EHFRQVLGHUHGDQGLIVRLWZLOOEH
GHWDLOHGLQWKH5$3
7UHDWPHQWE\SURJQRVWLFIDFWRUVLQWHUDFWLRQVZLOOEHVSHFLILFDOO\LQYHVWLJDWHGLQVHFRQGDU\
PRGHOV
+DQGOLQJRIWUHDWPHQWZLWKGUDZDOWUHDWPHQWZLWKGUDZDOZLOOEHFRQVLGHUHGDVDIDLOXUH
DQGWKHSULPDU\HQGSRLQWDWWKHWUHDWPHQWZLWKGUDZDOWLPHZLOOEHDVVHVVHGEDVHGRQWKH
ODVWDYDLODEOH$&7SRVWUDQGRPL]DWLRQVFRUHEHIRUHZLWKGUDZDO2IQRWHDFKDQJHLQWKH
GRVHUHJLPHQZLOOQRWEHFRQVLGHUHGDVDWUHDWPHQWIDLOXUH
+DQGOLQJRIPLVVLQJGDWDDVDJHQHUDOUXOHPLVVLQJGDWDZLOOQRWEHUHSODFHG
1HYHUWKHOHVVVHQVLWLYLW\DQDO\VHVUHJDUGLQJWKHSULPDU\DQGNH\VHFRQGDU\HQGSRLQWZLOO
UHSODFHPLVVLQJ$&7DVVHVVPHQWVE\WKHODVWDYDLODEOHSRVWUDQGRPL]DWLRQ$&7YDOXH
LHEDVHGRQWKHODVWREVHUYDWLRQFDUULHGIRUZDUGPHWKRG
7KHVWXG\LVDGHTXDWHO\SRZHUHGIRUWKHSULPDU\DQGWKHNH\VHFRQGDU\HQGSRLQWLHWR
VKRZQRQLQIHULRULW\RI))9,WRFXUUHQW,&6/$%$DW:HHN9LVLWDQGDW:HHN
9LVLWFRQVLGHULQJDQRQLQIHULRULW\PDUJLQRI2WKHUVHFRQGDU\HQGSRLQWVDUHQRW
QHFHVVDULO\DGHTXDWHO\SRZHUHGDQGDGHVFULSWLYHDQDO\VLVZLOORQO\EHSURSRVHGIRUWKHVH
HQGSRLQWV
7KHSULPDU\HIILFDF\DQDO\VLVSRSXODWLRQVHWLVGHILQHGDVDOOVXEMHFWVEHORQJLQJWRWKH
,QWHQWWR7UHDWSRSXODWLRQ,77ZKLFKLQFOXGH DOOVXEMHFWVZKRKDYHEHHQUDQGRPLVHG
DQGUHFHLYHGDWOHDVWRQHSUHVFULSWLRQRIVWXG\PHGLFDWLRQHJ))9,RUXVXDO
,&6/$%$LQKDODWLRQSRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\
(DFKVXEMHFWZLOOFRPSOHWHWKH$&7DW9LVLW5DQGRPLVDWLRQ:HHN9LVLWDQG
:HHN9LVLW$&7VFRUHVZLOODOVREHDVVHVVHGDW:HHN9LVLWDQGDW:HHN
9LVLWDQGDWWKHZLWKGUDZDOWLPHLIDQ\

3ULPDU\$QDO\VHV
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7WRWDO
VFRUHDVVHVVHGDW:HHN9LVLW
7KHSULPDU\SRSXODWLRQRIDQDO\VLVZLOOEHWKH,77SRSXODWLRQ
,IWUHDWPHQWLVZLWKGUDZQWKHQWKHPLVVLQJ$&7VFRUHDWWKHQHDUHVWYLVLWDIWHUWUHDWPHQW
ZLWKGUDZDOZLOOEHUHSODFHGE\WKH$&7VFRUHDVVHVVHGDWZLWKGUDZDOWLPH,IQR$&7

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
61
VFRUHLVDVVHVVHGDWZLWKGUDZDOWLPHWKHQWKH$&7PLVVLQJVFRUHDWWKHQHDUHVWYLVLWDIWHU
WUHDWPHQWZLWKGUDZDOZLOOQRWEHUHSODFHG

1RQLQIHULRULW\WHVWLQJ
7KHQRQLQIHULRULW\RI))9,YHUVXVDQ\RWKHU,&6/$%$'3,FRPSDUDWRUZLOOEH
SULPDULO\WHVWHGLQDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFK7KHPRGHOZLOO
LQFOXGHIDFWRUVDQGFRYDULDWHVDVIROORZWUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN
DQG:HHNEDVHOLQH $&7WUHDWPHQWE\YLVLWLQWHUDFWLRQEDVHOLQH$&7E\YLVLW
LQWHUDFWLRQJHQGHUDJHDQGSDWLHQWZLOOEHILWWHGDVDUDQGRPIDFWRU7KH5HVWULFWHG
0D[LPXP/LNHOLKRRG5(0/HVWLPDWLRQDSSURDFKZLOOEHXVHGDQGWKHGHIDXOW
FRYDULDQFHVWUXFWXUHZLOOEHXQVWUXFWXUHG&RQVLVWHQWZLWK0050PRGHOILWWLQJQR
H[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUD JLYHQWLPHSRLQWZLOOEHSHUIRUPHG7KH
FRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRUZLOO
EHHVWLPDWHGDW:HHN9LVLWLQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHGLIWKH
QRQLQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQ
WKHGLIIHUHQFHEHWZHHQ))9,DQGDQ\RWKHUFRPSDUDWRUSRVLWLYHYDOXHVRIWKHGLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\DQDO\VHV
D
+DQGOLQJPLVVLQJGDWD
:KLOHVXEMHFWVPLVVLQJ:HHN9LVLWGDWDEXWKDYLQJHDUOLHUGDWDZLOOEHLQFOXGHGLQ
WKH0050SULPDU\DQDO\VLVWKHLQWHUSUHWDELOLW\RIWKHUHVXOWVIURPWKHSULPDU\PRGHO
ZLOOGHSHQGRQWKHPLVVLQJGDWDVDWLVI\LQJWKH0LVVLQJDW5DQGRP0$57RVXSSRUW
WKHYDOLGLW\RIWKHFRQFOXVLRQVGUDZQIURPWKLVDQDO\VLVVHYHUDOVHQVLWLYLW\DQDO\VHVZLOO
EHSHUIRUPHGWRH[SORUHWKHGURSRXWSDWWHUQDQGLWVSRVVLEOHLPSDFWRQWUHDWPHQW
FRPSDULVRQV

0LVVLQJYDOXHVDW:HHN9LVLWZLOOEHUHSODFHGE\WKHSRVWUDQGRPL]DWLRQ
ODVWDYDLODEOHYDOXHHLWKHUWKHZHHNEDVHG$&7VFRUHRUWKH$&7VFRUHDW
WUHDWPHQWZLWKGUDZDOWLPHLIDQ\LHEDVHGRQWKH/DVW2EVHUYDWLRQ&DUULHG
)RUZDUGPHWKRG7KHFKDQJHIURPEDVHOLQHLQ$&7DW:HHN9LVLWZLOOEH
DQDO\]HGLQDQ$1&29$PRGHODGMXVWLQJIRUWUHDWPHQWDQGEDVHOLQH$&7VFRUH
7KHWUHDWPHQWHIIHFW))9,YHUVXVDQ\RWKHU,&6/$%$FRPSDUDWRUDQGLWV
FRUUHVSRQGLQJFRQILGHQFHLQWHUYDOZLOOEHHVWLPDWHGLQWKLVPRGHOWRWHVWWKH
QRQLQIHULRULW\K\SRWKHVLV

0XOWLSOHLPSXWDWLRQ0,DQDO\VHVXWLOL]LQJFRYDULDWHVNQRZQWREHSUHGLFWLYHRI
UHVSRQVHVHDVRQDWUDQGRPL]DWLRQREVHUYHGYDOXHRI$&7DW:HHNREVHUYHG
YDOXHRI$&7DW:HHN9LVLW2WKHUFRYDULDWHVPD\EHFRQVLGHUHGDQGLIVR
LWZLOOEHGHWDLOHGLQWKH5$3
6WHS)RUHDFKWUHDWPHQWJURXSVHSDUDWHO\PLVVLQJPHDVXUHPHQWVDUHLPSXWHGIRU
VXEMHFWVZLWKDEDVHOLQHPHDVXUHPHQWZKHUHWKHUHDUHPLVVLQJREVHUYDWLRQVDWHLWKHU
:HHNRU:HHNXVLQJWKHDERYHFRYDULDWHVDQGUHJUHVVLRQEDVHGLPSXWDWLRQPHWKRG
7KH0DUNRY&KDLQ0RQWH&DUOR0&0&PHWKRGIRU0,ZLOOEHXVHGDQGWHQVXFKVHWV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
62
RILPSXWHGGDWDZLOOEHFUHDWHGHDFKZLWKWKHREVHUYHGYDOXHVRULPSXWHGYDOXHVIRU
VXEMHFWVZLWKPLVVLQJREVHUYDWLRQV
6WHS(DFKLPSXWHGGDWDVHWZLOOEHDQDO\]HGXVLQJWKHSULPDU\0050PRGHO7KH
WUHDWPHQWHIIHFWIURPWKHVHDQDO\VHVZLOOWKHQEHSRROHGXVLQJVWDQGDUG0,WKHRU\WR
PDNHDQRYHUDOOLQIHUHQFH7KHGLIIHUHQFHLQWKHOHDVWVTXDUHVPHDQVEHWZHHQWKHWZR
JURXSVDW:HHN9LVLWDQGWKHFRUUHVSRQGLQJFRQILGHQFHLQWHUYDOIRUWKH
GLIIHUHQFHZLOOEHSUHVHQWHG
E
$ VHQVLWLYLW\ DQDO\VLV EDVHG RQ WKH VHPL SDUDPHWULF +RGJHV/HKPDQQ +/
DSSURDFKZLOOEHSURSRVHGWRDVVHVVWKHUREXVWQHVVRIWKH00500RGHOEDVHG
QRQLQIHULRULW\UHVXOWV7KH+/GLIIHUHQFHEHWZHHQJURXSVZLWKWKHFRUUHVSRQGLQJ
FRQILGHQFHLQWHUYDOZLOOEHSURYLGHG
F
6HQVLWLYLW\ DQDO\VHV IRU KDQGOLQJ WUHDWPHQW ZLWKGUDZDO ZKHQ WUHDWPHQW
ZLWKGUDZDORFFXUVDQDOWHUQDWLYHPHWKRGIRULPSXWLQJWKHPLVVLQJYDOXHDWWKH
QHDUHVWYLVLWDIWHUZLWKGUDZDOWLPHZLOOEHSURSRVHGWKHSULPDU\HQGSRLQWPLVVLQJ
YDOXHZLOOEHHVWLPDWHGE\WKHZRUVW$&7VFRUHREVHUYHGEHWZHHQEDVHOLQHYLVLW
LQFOXGHGDQGZLWKGUDZDOWLPHLQFOXGHG
G
7KH SULPDU\ DQDO\VLV LH EDVHG RQ WKH 0050 DSSURDFK DQG WKH VDPH
VHQVLWLYLW\DQDO\VHVSUHVHQWHGKHUHDERYHZLOOEHSHUIRUPHGRQWKH3HU3URWRFRO
SRSXODWLRQ
0RGHODVVXPSWLRQVFKHFNLQJ
D $VVXPSWLRQV XQGHUO\LQJ WKH 0050 UHVS $1&29$ IRU WKH VHQVLWLYLW\ DQDO\VLV
PRGHOUHVLGXDOQRUPDOLW\ OLQHDUUHODWLRQVKLSEHWZHHQUHVSRQVH DQGEDVHOLQH$&7
HWFZLOOEHFKHFNHGZLWKJUDSKLFDOPHWKRGVSORWVRIVWXGHQWL]HGUHVLGXDOVHWF
E %DVHOLQH$&7ZLOOEHFDWHJRUL]HGDFFRUGLQJWKHGLVWULEXWLRQTXDUWLOHVDQGWKHVDPH
0050PRGHOUHVS$1&29$IRUWKHVHQVLWLYLW\DQDO\VLVDGMXVWLQJIRUFDWHJRUL]HG
%DVHOLQH$&7ZLOOEHILWWHGDJDLQ
F 3RVVLEOHWUHDWPHQWE\FRYDULDWHVEDVHOLQH$&7EDVHOLQH$VWKPDWKHUDS\VHDVRQDW
UDQGRPLVDWLRQ LQWHUDFWLRQ ZLOO EH LQYHVWLJDWHG 0050 UHVS $1&29$ IRU WKH
VHQVLWLYLW\DQDO\VLVDGMXVWLQJIRUWKHVHDGGLWLRQDOLQWHUDFWLRQWHUPV
G 7KH LQIOXHQFH RI WKH FRYDULDWHV DQG SRWHQWLDO DGGLWLRQDO FRYDULDWHV RQ WKH RXWFRPH
ZLOOEHLQYHVWLJDWHG

6XSHULRULW\WHVWLQJ
,IQRQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI))9,
WRDQ\RWKHUFRPSDUDWRUZLOOEHWHVWHGDWWKHXVXDOWZRVLGHGQRPLQDOOHYHO RI
VLJQLILFDQFH
7KHVDPHPRGHOVDQGDQDO\VHVPHQWLRQHGDERYHZLOOEHXVHGWRDVVHVVWKHVXSHULRULW\
K\SRWKHVLV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
63

6HFRQGDU\$QDO\VHV
.H\VHFRQGDU\DQDO\VLV
7KHNH\VHFRQGDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7
WRWDOVFRUHDVVHVVHGDW:HHN9LVLW

1RQLQIHULRULW\WHVWLQJ
,IQRQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGDW:HHN9LVLWWKHQQRQLQIHULRULW\ZLOO
EHWHVWHGDW:HHNDWWKHWZRVLGHGQRPLQDOOHYHO,IQRQLQIHULRULW\LVQRW
DFFHSWHGDW:HHN9LVLWQRQLQIHULRULW\ZLOOQRWEHWHVWHGDW:HHN9LVLWDQG
DVVHVVHGRQDGHVFULSWLYHEDVLVRQO\
0RUHSUHFLVHO\WKHNH\VHFRQGDU\HQGSRLQWDVVHVVHGDW:HHN9LVLWZLOODOVREH
DQDO\]HGXVLQJDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFKZKHUHGDWDXSWR
DQGLQFOXGLQJ:HHN9LVLWZLOOEHXVHGLQWKHPRGHO7KHPRGHOZLOOLQFOXGH
IDFWRUVDQGFRYDULDWHVDVIROORZWUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN:HHN
:HHNDQG:HHNEDVHOLQH $&7WUHDWPHQWE\YLVLWLQWHUDFWLRQEDVHOLQH$&7E\
YLVLWLQWHUDFWLRQJHQGHUDJHDQGSDWLHQWZLOOEHILWWHGDVDUDQGRPIDFWRU7KH5HVWULFWHG
0D[LPXP/LNHOLKRRG5(0/HVWLPDWLRQDSSURDFKZLOOEHXVHGDQGWKHGHIDXOW
FRYDULDQFHVWUXFWXUHZLOOEHXQVWUXFWXUHG&RQVLVWHQWZLWK0050PRGHOILWWLQJQR
H[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUDJLYHQWLPHSRLQWZLOOEHSHUIRUPHG7KH
FRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRUZLOO
EHHVWLPDWHGDW:HHN LQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHG LIWKHQRQ
LQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQWKH
GLIIHUHQFHEHWZHHQ))9,DQGDQ\RWKHUFRPSDUDWRUSRVLWLYHYDOXHVRIWKHGLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\ DQDO\VHV WKH VDPH VHQVLWLYLW\ DQDO\VHV DV WKRVH GHVFULEHG DERYH IRU WKH
SULPDU\HQGSRLQWZLOOEHSHUIRUPHGIRUWKHNH\VHFRQGDU\HIILFDF\HQGSRLQW
0RGHODVVXPSWLRQVFKHFNLQJWKHDQDO\VHVSURSRVHGWRFKHFNPRGHODVVXPSWLRQVIRUWKH
DQDO\VLVRIWKHNH\VHFRQGDU\HIILFDF\HQGSRLQWZLOOEHWKHVDPHDVWKRVHGHVFULEHGDERYH
IRUWKHSULPDU\HQGSRLQW

6XSHULRULW\WHVWLQJ
,IQRQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI))9,
YHUVXVDQ\RWKHUFRPSDUDWRUZLOOEHWHVWHGDWWKHXVXDOWZRVLGHGQRPLQDOOHYHORI
VLJQLILFDQFH
7KHVDPHPRGHOVDQGDQDO\VHVPHQWLRQHGDERYHZLOOEHXVHGWRDVVHVVWKHVXSHULRULW\
K\SRWKHVLV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
64
2WKHUVHFRQGDU\DQDO\VHV
3URSHUXVHRIWKHPHGLFDOGHYLFH
7KHRWKHUNH\VHFRQGDU\HQGSRLQWZLOOEHWKHFRUUHFWXVHRIWKHLQKDOHUGHYLFHDVVHVVHGDW
UDQGRPLVDWLRQ9LVLWDW:HHN9LVLWDQGDW:HHN9LVLW7KHGHYLFHZLOO
EHFRQVLGHUHGDVDGHTXDWHO\XVHGLIWKHSDWLHQWGLGQ¶WPDNHDQ\FULWLFDOHUURU RUQRQ
FULWLFDOHUURU DWWKHFRUUHVSRQGLQJYLVLWVUDQGRPLVDWLRQ>9LVLW@ZHHN>9LVLW@DQG
ZHHN>9LVLW@3HUFHQWDJHV RIVXEMHFWVFRUUHFWO\XVLQJWKHGHYLFHZLOOEHFDOFXODWHG
ZLWKLQHDFKJURXS$FRUUHVSRQGLQJFRQILGHQFHLQWHUYDORIWKHGLIIHUHQFHLQ
SHUFHQWDJHVZLOODOVREHSURYLGHG)XUWKHUPRUHWKHSHUFHQWDJHRIVXEMHFWVZLWKRYHUDOO
HUURUDWOHDVWRQHFULWLFDOHUURUDQGDWOHDVWRQHQRQFULWLFDOHUURUZLOOEHSUHVHQWHGE\
WUHDWPHQWJURXSDORQJZLWKWKHSHUFHQWDJHPDNLQJHDFKVSHFLILFHUURU$GGLWLRQDO
H[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOOEHGHWDLOHGLQWKH5$3(YHQLIWHVWV
ZLOOEHSHUIRUPHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV

2WKHU$QDO\VHV
2WKHU$QDO\VHV
7KHDQDO\VLVRIWKHRWKHUHQGSRLQWVGHILQHGLQWKLVVHFWLRQZLOOEHSURYLGHGIRU
H[SORUDWRU\SXUSRVHVRQO\$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOO
EHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGDQGFRQILGHQFHLQWHUYDOVZLOO
EHSURYLGHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV
&KDQJHIURPEDVHOLQHLQSUHGRVHWURXJK)(9
5HVXOWVZLOOEHVXPPDUL]HGIRUHDFKJURXSDW:HHN9LVLW0RUHGHWDLOZLOOEH
SURYLGHGLQWKH5$3
5HVSRQVHWRWUHDWPHQW
!
%LQDU\UHVSRQVH GHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW25DSRLQW
LQFUHDVHIURPEDVHOLQHLQ$&7FKDQJH
7KHUHVSRQGHUDQDO\VHVZLOOEHFRQGXFWHGXVLQJDORJLVWLFUHJUHVVLRQPRGHODWDJLYHQ
9LVLWRU3KRQH&DOODGMXVWLQJIRUWUHDWPHQWDQGVWUDWLILFDWLRQIDFWRUVEDVHOLQH$&7VFRUH
FDWHJRUL]HGLQWRWZRFODVVHVEDVHOLQHDVWKPDWKHUDS\DQGSRWHQWLDOO\VHDVRQDW
UDQGRPL]DWLRQ7UHDWPHQWE\VWUDWLILFDWLRQIDFWRUVLQWHUDFWLRQHIIHFWVZLOOEHIXUWKHU
LQYHVWLJDWHGLQDGGLWLRQDOORJLVWLFPRGHOVDGMXVWLQJIRUWKHVHVSHFLILFHIIHFWV
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW
7KHIUHTXHQF\DQGWKHSHUFHQWDJHRIVXEMHFWVZLWK$&7VFRUHDWDJLYHQYLVLWZLOOEH
GHVFULEHGE\WUHDWPHQWJURXS0RUHGHWDLOZLOOEHSURYLGHGLQWKH5$3
!
&KDQJHIURPEDVHOLQHLQLQGLYLGXDOTXHVWLRQVFRUHVIRU$&7 DWDJLYHQYLVLW
)RU HDFK TXHVWLRQ WKH VWDWLVWLFDO SDUDPHWHUV RI WKH FKDQJHV ZLOO EH VXPPDUL]HG E\
WUHDWPHQWJURXS0RUHGHWDLOZLOOEHSURYLGHGLQWKH5$3

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
65
&RPSOLDQFHZLWKVWXG\PHGLFDWLRQ DQGVHOIUHSRUWHGDGKHUHQFHWRVWXG\PHGLFDWLRQ
!
2YHUDOOWUHDWPHQWFRPSOLDQFHZLWKVWXG\PHGLFDWLRQIURPUDQGRPLVDWLRQ'D\WR
:HHN  9LVLW  IURP :HHN  9LVLW  WR :HHN  9LVLW  DQG IURP
UDQGRPLVDWLRQ'D\WR:HHN9LVLWZLOOEHGHVFULEHGE\WUHDWPHQWJURXS
!
7KHVFRUHIRU0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$DW'D\
:HHNDQG:HHNZLOOEHGHVFULEHGE\WUHDWPHQWJURXS
6HYHUHDVWKPDH[DFHUEDWLRQV
1XPEHURIVXEMHFWVZLWKDWOHDVWRQHVHYHUHH[DFHUEDWLRQQXPEHURIVHYHUHDVWKPD
H[DFHUEDWLRQDQGDQQXDOH[DFHUEDWLRQUDWHRYHUWKHVWXG\SHULRG
$VHYHUHDVWKPDH[DFHUEDWLRQLVGHILQHGDVGHWHULRUDWLRQRIDVWKPDUHTXLULQJWKHXVHRI
V\VWHPLFFRUWLFRVWHURLGV WDEOHWVVXVSHQVLRQRULQMHFWLRQZLWKRUZLWKRXWDQWLELRWLFV
SUHVFULEHGRUDQLQSDWLHQWKRVSLWDOLVDWLRQRUHPHUJHQF\GHSDUWPHQWYLVLWGXHWRDVWKPD
WKDWUHTXLUHGV\VWHPLFFRUWLFRVWHURLGVRUDQWLELRWLFV 
7KHQXPEHUDQGSHUFHQWDJHRIVXEMHFWVH[SHULHQFLQJDQDVWKPDH[DFHUEDWLRQGXULQJWKH
VWXG\SHULRGZLOOEHVXPPDUL]HGIRUHDFKWUHDWPHQWJURXS/LVWLQJZLOOEHSURYLGHGWR
LQFOXGHWKHSULPDU\FDXVHVRIWKHH[DFHUEDWLRQ
,IIHDVLEOHLHLIWKHQXPEHURIH[DFHUEDWLRQHYHQWVLVKLJKHQRXJKPHDQDQQXDOUDWHRI
DVWKPDH[DFHUEDWLRQZLOOEHDQDO\VHGXVLQJDJHQHUDOLVHGOLQHDUPRGHODVVXPLQJWKH
QHJDWLYHELQRPLDOGLVWULEXWLRQZLWKWKHORJDULWKPRIWLPHRQWUHDWPHQWDVDQRIIVHW
YDULDEOH7KHDGMXVWHGPHDQUDWHVSHU\HDUWUHDWPHQWUDWLRDQGDVVRFLDWHGSYDOXHDQG
FRQILGHQFHLQWHUYDOZLOOEHSUHVHQWHG
+HDOWK5HODWHG4XDOLW\RI/LIHDQG+HDOWKVWDWXV
!
$QLQFUHDVHIURPEDVHOLQHRILQ$4/4VWRWDOVFRUHDW:HHN9LVLW
!
$QLQFUHDVHIURPEDVHOLQHRILQ$4/4VHQYLURQPHQWDOVWLPXOLGRPDLQVFRUH
DW:HHN9LVLW
!
&KDQJH IURP EDVHOLQH LQ WRWDO VFRUH DQG GRPDLQ VFRUHV RI $4/46 DW :HHN 
9LVLW
!
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ LQFUHDVH IURP EDVHOLQH RI   LQ $4/46
,QGLYLGXDOGRPDLQVFRUHVDW:HHN9LVLW
!
+HDOWKVWDWXVXVLQJWKH(XUR4RO4XHVWLRQQDLUH (4'DW:HHN9LVLW
3DWLHQWV6DWLVIDFWLRQDQG3UHIHUHQFHZLWKWKHLQKDOHU3$6$3 4XHVWLRQQDLUHVHH
$SSHQGL[
7KHRYHUDOOLQKDOHUVDWLVIDFWLRQDQGSUHIHUHQFHZLOOEHPHDVXUHGDW:HHN9LVLW
7KH3$6$3VFRUHZLOOEHVXPPDULVHGE\WUHDWPHQWJURXS
)XUWKHUDQDO\VHVZLOOEHVSHFLILHGLQWKH5HSRUW$QDO\VLV3ODQ

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
66
6XEJURXS $QDO\VHV
6XEJURXSVXPPDULHVDQGRUDQDO\VHVZLOODOVREHSURYLGHGZKHQDSSURSULDWHIRU
HIILFDF\DQGVDIHW\HQGSRLQWVEDVHGRQEDVHOLQHGLVHDVHFKDUDFWHULVWLFV
$GGLWLRQDODQDO\VHVFRXOGEHFDUULHGRXWXVLQJDSSURSULDWHPHWKRGVWRDFFRXQWIRU
FKDQJHVLQWUHDWPHQWGXULQJWKHFRXUVHRIWKHVWXG\)XUWKHUGHWDLOVZLOOEHSURYLGHGLQ
WKHDQDO\VLVSODQ
7KHGHWDLOVZLOOEHSURYLGHGLQWKH5$3
6DIHW\$QDO\VHV
6DIHW\GDWDZLOOEHVXPPDUL]HGDQGRUOLVWHGE\WUHDWPHQWJURXSDQGE\YLVLWIRUWKH
6DIHW\SRSXODWLRQ
([WHQWRI([SRVXUH
([WHQWRIH[SRVXUHWRVWXG\WUHDWPHQWLHQXPEHURIGD\VRQUDQGRPLVHGWUHDWPHQWZLOO
EHVXPPDULVHGE\WUHDWPHQWJURXSXVLQJPHDQVWDQGDUGGHYLDWLRQPHGLDQPLQLPXP
DQGPD[LPXP,QDGGLWLRQGXUDWLRQRIVXEMHFWH[SRVHGWRVWXG\GUXJZLOOEH VXPPDULVHG
DFURVVWUHDWPHQWJURXSV
$GYHUVH'UXJ5HDFWLRQV
$GYHUVHGUXJUHDFWLRQVGXULQJWKHWUHDWPHQWSHULRGDQGGXULQJWKHSRVWWUHDWPHQWSHULRG
ZLOOEHVXPPDULVHGDQGGLVSOD\HGE\WUHDWPHQWJURXS$GYHUVHGUXJUHDFWLRQVGXULQJWKH
WUHDWPHQWSHULRGLQFOXGHWKRVHZLWKDGDWHRIRQVHWRQWKHGDWHRIVWXG\WUHDWPHQW
LQLWLDWLRQWRRQHGD\DIWHUVWXG\WUHDWPHQWWHUPLQDWLRQ
7KHDGYHUVHGUXJUHDFWLRQVZLOOEHFRGHGXVLQJWKH0HGLFDO'LFWLRQDU\IRU5HJXODWRU\
$FWLYLWLHV0HG'5$DQGZLOOEHUHSRUWHGXVLQJWKHSULPDU\6\VWHP2UJDQ&ODVV62&
DQG3UHIHUUHG7HUP3UHIHUUHG7HUPVZLOOEHVXPPDULVHGZLWKLQWKHSULPDU\62&7KH
UHODWLRQVKLSRISULPDU\62&SUHIHUUHGWHUPVDQGYHUEDWLPWH[WZLOOEHOLVWHG
7KHQXPEHURIVXEMHFWVZLWKRQHRUPRUHHYHQWVRIDQ\W\SHZLOOEHFDOFXODWHG5HVXOWV
ZLOOEHGLVSOD\HGLQWKHRUGHURIGHFUHDVLQJIUHTXHQF\ERWKDFURVVSULPDU\62&DQG
ZLWKLQSULPDU\62&
$GYHUVHGUXJUHDFWLRQVGXULQJWKHVWXG\SHULRGZLOODOVREHOLVWHG7KHGHPRJUDSKLF
GHWDLOVHJDJHVH[DQGWKHGHWDLOVRQLQGLYLGXDODGYHUVHHYHQWVZLOOEHLQFOXGHGLQ
WKHVHOLVWLQJV/LVWLQJVZLOOEHVRUWHGZLWKLQVXEMHFWE\WKHDGYHUVHGUXJUHDFWLRQGDWHRI
RQVHW
6LPLODUVXPPDULHVDQGOLVWLQJVZLOOEHSURYLGHGIRUDGYHUVHHYHQWVOHDGLQJWRZLWKGUDZDO
IURPVWXG\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
67
'HDWKVDQG6HULRXV$GYHUVH(YHQWV
'HDWKVDQGVHULRXVDGYHUVHHYHQWVGXULQJWKHVWXG\SHULRGZLOOEHOLVWHG6HULRXVDGYHUVH
HYHQWVGXULQJWKHVWXG\SHULRGZLOODOVREHVXPPDULVHGE\WUHDWPHQWJURXS
$Q\SUHJQDQFLHVVHULRXVDGYHUVHHYHQWVDQGGHDWKVUHSRUWHGGXULQJWKLVVWXG\ZLOODOVR
EHVXPPDULVHGLQFDVHQDUUDWLYHVZULWWHQE\*6.*&63SHUVRQQHO
2WKHUVDIHW\SDUDPHWHUV
$OORWKHUVVDIHW\SDUDPHWHUVZLOOEHOLVWHGDQGVXPPDUL]HG
0RUHVSHFLILFDOO\WKHYLWDOVLJQV%0,SXOVHUDWHV\VWROLFEORRGSUHVVXUHDQGGLDVWROLF
EORRGSUHVVXUHZLOOEHVXPPDUL]HGE\YLVLWDQGWUHDWPHQWJURXS
*HQHWLFUHVHDUFK
,QIRUPDWLRQUHJDUGLQJJHQHWLFUHVHDUFKLVLQFOXGHGLQ$SSHQGL[

678'<*29(51$1&(&216,'(5$7,216

3RVWLQJRI,QIRUPDWLRQRQ3XEOLFO\$YDLODEOH&OLQLFDO7ULDO
5HJLVWHUV
6WXG\LQIRUPDWLRQIURPWKLVSURWRFROZLOOEHSRVWHGRQSXEOLFO\DYDLODEOHFOLQLFDOWULDO
UHJLVWHUVEHIRUHHQUROPHQWRIVXEMHFWVEHJLQV

5HJXODWRU\DQG(WKLFDO&RQVLGHUDWLRQV,QFOXGLQJWKH
,QIRUPHG&RQVHQW3URFHVV
3ULRUWRLQLWLDWLRQRIDVWXG\VLWH*6.ZLOOREWDLQIDYRXUDEOHRSLQLRQDSSURYDOIURPWKH
DSSURSULDWHUHJXODWRU\DJHQF\WRFRQGXFWWKHVWXG\LQDFFRUGDQFHZLWK,&+*RRG&OLQLFDO
3UDFWLFH*&3DQGDSSOLFDEOHFRXQWU\VSHFLILFUHJXODWRU\UHTXLUHPHQWV
7KHVWXG\ZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWKDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV
7KHVWXG\ZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWK,&+*&3DOODSSOLFDEOHVXEMHFWSULYDF\
UHTXLUHPHQWVDQGWKHHWKLFDOSULQFLSOHVWKDW DUHRXWOLQHGLQWKH'HFODUDWLRQRI+HOVLQNL
LQFOXGLQJEXWQRWOLPLWHGWR
!
,QVWLWXWLRQDO 5HYLHZ %RDUG ,5%,QGHSHQGHQW (WKLFV &RPPLWWHH ,(& UHYLHZ
DQG IDYRXUDEOH RSLQLRQDSSURYDO RI VWXG\ SURWRFRO DQG DQ\ VXEVHTXHQW
DPHQGPHQWV
!
6XEMHFWLQIRUPHGFRQVHQW
!
,QYHVWLJDWRUUHSRUWLQJUHTXLUHPHQWV
*6.ZLOOSURYLGHIXOOGHWDLOVRIWKHDERYHSURFHGXUHVHLWKHUYHUEDOO\LQZULWLQJRUERWK
:ULWWHQLQIRUPHGFRQVHQWPXVWEHREWDLQHGIURPHDFKVXEMHFWSULRUWRSDUWLFLSDWLRQLQWKH
VWXG\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
68

4XDOLW\&RQWURO6WXG\ 0RQLWRULQJ
,QDFFRUGDQFHZLWKDSSOLFDEOHUHJXODWLRQV*&3DQG*6.SURFHGXUHV*6.PRQLWRUV
ZLOOFRQWDFWWKHVLWHSULRUWRWKHVWDUWRIWKHVWXG\WRUHYLHZZLWKWKHVLWHVWDIIWKHSURWRFRO
VWXG\UHTXLUHPHQWVDQGWKHLUUHVSRQVLELOLWLHVWRVDWLVI\UHJXODWRU\HWKLFDODQG*6.
UHTXLUHPHQWV:KHQUHYLHZLQJGDWDFROOHFWLRQSURFHGXUHVWKHGLVFXVVLRQZLOOLQFOXGH
LGHQWLILFDWLRQDJUHHPHQWDQGGRFXPHQWDWLRQRIGDWDLWHPVIRUZKLFKPHGLFDOUHFRUGVZLOO
VHUYHDVWKHVRXUFHGRFXPHQW
*6.ZLOOPRQLWRUWKHVWXG\WRHQVXUHWKDWWKH
!
'DWDDUHDXWKHQWLFDFFXUDWHDQGFRPSOHWH
!
6DIHW\DQGULJKWVRIVXEMHFWVDUHEHLQJSURWHFWHG
!
6WXG\LVFRQGXFWHGLQDFFRUGDQFHZLWKWKHFXUUHQWO\DSSURYHGSURWRFRODQGDQ\RWKHU
VWXG\DJUHHPHQWV*&3DQGDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV
7KH,QYHVWLJDWRUDQGWKHKHDGRIWKHPHGLFDOLQVWLWXWLRQZKHUHDSSOLFDEOHDJUHHVWR
DOORZWKHPRQLWRUGLUHFWDFFHVVWRDOOUHOHYDQWGRFXPHQWV

4XDOLW\$VVXUDQFH
7RHQVXUHFRPSOLDQFHZLWK*&3DQGDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV*6.PD\
FRQGXFWDTXDOLW\DVVXUDQFHDVVHVVPHQWDQGRUDXGLWRIWKHVLWHUHFRUGVDQGWKHUHJXODWRU\
DJHQFLHVPD\FRQGXFWDUHJXODWRU\LQVSHFWLRQDWDQ\WLPHGXULQJRUDIWHUFRPSOHWLRQRI
WKHVWXG\,QWKHHYHQWRIDQDVVHVVPHQWDXGLWRULQVSHFWLRQWKHLQYHVWLJDWRU DQG
LQVWLWXWLRQPXVWDJUHHWRJUDQWWKHDGYLVRUVDXGLWRUVDQGLQVSHFWRUVGLUHFWDFFHVVWR
DOOUHOHYDQWGRFXPHQWVDQGWRDOORFDWHWKHLUWLPHDQGWKHWLPHRIWKHLUVWDIIWRGLVFXVVWKH
FRQGXFWRIWKHVWXG\DQ\ILQGLQJVUHOHYDQWLVVXHVDQGWRLPSOHPHQWDQ\FRUUHFWLYHDQGRU
SUHYHQWDWLYHDFWLRQVWRDGGUHVVDQ\ILQGLQJVLVVXHVLGHQWLILHG

6WXG\DQG6LWH&ORVXUH
8SRQFRPSOHWLRQRUWHUPLQDWLRQRIWKHVWXG\WKH*6.PRQLWRUZLOOFRQGXFWVLWHFORVXUH
DFWLYLWLHVZLWKWKH,QYHVWLJDWRURUVLWHVWDIIDVDSSURSULDWHLQDFFRUGDQFHZLWKDSSOLFDEOH
UHJXODWLRQV*&3DQG*6.6WDQGDUG2SHUDWLQJ3URFHGXUHV
*6.UHVHUYHVWKHULJKWWRWHPSRUDULO\VXVSHQGRUWHUPLQDWHWKHVWXG\DWDQ\WLPHIRU
UHDVRQVLQFOXGLQJEXWQRWOLPLWHGWRVDIHW\LVVXHVHWKLFDOLVVXHVRUVHYHUHQRQ
FRPSOLDQFH,I*6.GHWHUPLQHVWKDWVXFKDFWLRQLVUHTXLUHG*6.ZLOOGLVFXVVWKHUHDVRQV
IRUWDNLQJVXFKDFWLRQZLWKWKHLQYHVWLJDWRURUKHDGRIWKHPHGLFDOLQVWLWXWLRQZKHUH
DSSOLFDEOH:KHQIHDVLEOH*6.ZLOOSURYLGHDGYDQFHQRWLFHWRWKH,QYHVWLJDWRURUKHDG
RIWKHPHGLFDOLQVWLWXWLRQRIWKHLPSHQGLQJDFWLRQ
,IDVWXG\LVVXVSHQGHGRUWHUPLQDWHGIRUVDIHW\UHDVRQV*6.ZLOOSURPSWO\LQIRUPDOO
,QYHVWLJDWRUVKHDGVRIWKHPHGLFDOLQVWLWXWLRQVZKHUHDSSOLFDEOHDQGRULQVWLWXWLRQV
FRQGXFWLQJ WKHVWXG\*6.ZLOODOVRSURPSWO\LQIRUPWKHUHOHYDQWUHJXODWRU\DXWKRULWLHV
RIWKHVXVSHQVLRQWHUPLQDWLRQDORQJZLWKWKHUHDVRQVIRUVXFKDFWLRQ:KHUHUHTXLUHGE\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
69
DSSOLFDEOHUHJXODWLRQVWKH,QYHVWLJDWRURUKHDGRIWKHPHGLFDOLQVWLWXWLRQPXVWLQIRUPWKH
,(&SURPSWO\DQGSURYLGHWKHUHDVRQVIRUWKHVXVSHQVLRQWHUPLQDWLRQ

5HFRUGV5HWHQWLRQ
)ROORZLQJFORVXUHRIWKHVWXG\WKH,QYHVWLJDWRURUKHDGRIWKHPHGLFDOLQVWLWXWLRQZKHUH
DSSOLFDEOHPXVWPDLQWDLQDOOVLWHVWXG\UHFRUGVH[FHSWIRUWKRVHUHTXLUHGE\ORFDO
UHJXODWLRQVWREHPDLQWDLQHGHOVHZKHUHLQDVDIHDQGVHFXUHORFDWLRQ7KHUHFRUGVPXVW
EHHDVLO\DFFHVVLEOHZKHQQHHGHGHJIRUD*6.DXGLWRUUHJXODWRU\LQVSHFWLRQDQG
PXVWEHDYDLODEOHIRUUHYLHZLQFRQMXQFWLRQZLWKDVVHVVPHQWRIWKHIDFLOLW\VXSSRUWLQJ
V\VWHPVDQGUHOHYDQWVLWHVWDII
:KHUHSHUPLWWHGE\ORFDOODZVUHJXODWLRQVRULQVWLWXWLRQDOSROLF\VRPHRUDOORIWKH
UHFRUGVPD\EHPDLQWDLQHGLQDIRUPDWRWKHUWKDQKDUGFRS\HJPLFURILFKHVFDQQHG
HOHFWURQLFKRZHYHUFDXWLRQPXVWEHH[HUFLVHGEHIRUHVXFKDFWLRQLVWDNHQ7KH
,QYHVWLJDWRUPXVWHQVXUHWKDWDOOUHSURGXFWLRQVDUHOHJLEOHDQGDUHDWUXHDQGDFFXUDWH
FRS\RIWKHRULJLQDO,QDGGLWLRQWKH\PXVWPHHWDFFHVVLELOLW\DQGUHWULHYDOVWDQGDUGV
LQFOXGLQJUHJHQHUDWLRQRIDKDUGFRS\LIUHTXLUHG7KH,QYHVWLJDWRUDQG*6.PXVWDOVR
HQVXUHWKDWDQDFFHSWDEOHEDFNXSRIWKHUHSURGXFWLRQVH[LVWVDQGWKDWWKHUHLVDQ
DFFHSWDEOHTXDOLW\FRQWUROSURFHGXUHLQSODFHIRUFUHDWLQJWKHUHSURGXFWLRQV
*6.ZLOOLQIRUPWKH,QYHVWLJDWRURIWKHWLPHSHULRGIRUUHWDLQLQJWKHVLWHUHFRUGVLQRUGHU
WRFRPSO\ZLWKDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV7KHPLQLPXPUHWHQWLRQWLPHZLOO
PHHWWKHVWULFWHVWVWDQGDUGDSSOLFDEOHWRDSDUWLFXODUVLWHDVGLFWDWHGE\ORFDO
ODZVUHJXODWLRQV*6.VWDQGDUGRSHUDWLQJSURFHGXUHVDQGRULQVWLWXWLRQDOUHTXLUHPHQWV
7KH*3,QYHVWLJDWRUPXVWQRWLI\*6.RIDQ\FKDQJHVLQWKHDUFKLYDODUUDQJHPHQWV
LQFOXGLQJEXWQRWOLPLWHGWRDUFKLYDORIUHFRUGVDWDQRIIVLWHIDFLOLW\RUWUDQVIHURI
RZQHUVKLSRIWKHUHFRUGVLQWKH HYHQWWKDWWKH,QYHVWLJDWRULVQRORQJHUDVVRFLDWHGZLWKWKH
VLWH

3URYLVLRQRI6WXG\5HVXOWVWR,QYHVWLJDWRUV3RVWLQJRI
,QIRUPDWLRQRQ3XEOLFDOO\$YDLODEOH&OLQLFDO7ULDOV5HJLVWHUV
DQG3XEOLFDWLRQ
:KHUHUHTXLUHGE\DSSOLFDEOHUHJXODWRU\UHTXLUHPHQWVDQ,QYHVWLJDWRUVLJQDWRU\ZLOOEH
LGHQWLILHGIRUWKHDSSURYDORIWKHFOLQLFDOVWXG\UHSRUW7KH,QYHVWLJDWRUVLJQDWRU\ZLOOEH
SURYLGHGUHDVRQDEOHDFFHVVWRVWDWLVWLFDOWDEOHVILJXUHVDQGUHOHYDQWUHSRUWVDQGZLOOKDYH
WKHRSSRUWXQLW\WRUHYLHZWKHFRPSOHWHVWXG\UHVXOWVDWD*6.VLWHRURWKHUPXWXDOO\
DJUHHDEOHORFDWLRQ
*6.ZLOODOVRSURYLGHWKH,QYHVWLJDWRUZLWKWKHIXOOVXPPDU\RIWKHVWXG\UHVXOWV7KH
,QYHVWLJDWRULVHQFRXUDJHGWRVKDUHWKHVXPPDU\UHVXOWVZLWKWKHVWXG\VXEMHFWVDV
DSSURSULDWH
*6.DLPVWRSRVWDUHVXOWVVXPPDU\WRWKH*6.&OLQLFDO6WXG\5HJLVWHUDQGRWKHU
SXEOLFO\DYDLODEOHUHJLVWHUVQRODWHUWKDQPRQWKVDIWHUWKHODVWVXEMHFW¶VODVWYLVLW/6/9
>WKLVDSSOLHVWRHDFKGDWDDQDO\VLVSKDVHIRUVWXGLHVZLWKPXOWLSOHSKDVHVHJSULPDU\
DQDO\VLVIROORZXSDQDO\VLVHWF@,QDGGLWLRQWKHDLPLVWRVXEPLWDPDQXVFULSWWRDSHHU

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
70
UHYLHZHGMRXUQDOIRUSXEOLFDWLRQZLWKLQPRQWKVRI/6/9*6.DOVRDLPVWRSXEOLVK
WKHIXOOVWXG\SURWRFRORQWKH*6.&OLQLFDO6WXG\5HJLVWHUDWWKHWLPHWKHUHVXOWVRIWKH
VWXG\DUHSXEOLVKHGDVDPDQXVFULSWLQWKHVFLHQWLILFOLWHUDWXUH
:KHQPDQXVFULSWSXEOLFDWLRQLQDSHHUUHYLHZHGMRXUQDOLVQRWIHDVLEOHIXUWKHUVWXG\
LQIRUPDWLRQZLOOEHSRVWHGWRWKH*6.&OLQLFDO6WXG\5HJLVWHUWRVXSSOHPHQWWKHUHVXOWV
VXPPDU\
$PDQXVFULSWZLOOEHSURJUHVVHGIRUSXEOLFDWLRQLQWKHVFLHQWLILFOLWHUDWXUHLIWKHUHVXOWV
SURYLGHLPSRUWDQWVFLHQWLILFRUPHGLFDONQRZOHGJH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
71

5()(5(1&(6
%ULWLVK*XLGHOLQHRQWKH0DQDJHPHQWRI$VWKPD%ULWLVK7KRUDFLF6RFLHW\$QDWLRQDO
FOLQLFDOJXLGHOLQHLYLY
&RKHQ-/0DQQ'0:LVQLYHVN\-3+RUQH5/HYHQWKDO+0XVXPHFL6]DER7-+DOP
($$VVHVVLQJWKHYDOLGLW\RIVHOIUHSRUWHGPHGLFDWLRQDGKHUHQFHDPRQJLQQHUFLW\
DVWKPDWLFDGXOWVWKH0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD$QQ$OOHUJ\
$VWKPD,PPXQRO
'RODQ30RGHOLQJYDOXDWLRQVIRU(XUR4ROKHDOWKVWDWHV0HG&DUH

)DQWD&+'UXJ7KHUDS\$VWKPD1HZ(QJO-0HG
*,1$KWWSZZZJLQDVWKPDRUJORFDOXSORDGVILOHV*,1$B5HSRUWB0DUFKSGI
*OD[R6PLWK.OLQH'RFXPHQW1XPEHU 50)OXWLFDVRQH)XURDWH
9LODQWHURO,QYHVWLJDWRU
V%URFKXUH-XQ
*OREDO,QLWLDWLYHIRU$VWKPD*,1$*OREDO6WUDWHJ\IRU$VWKPD0DQDJHPHQWDQG
3UHYHQWLRQ*,1$ZZZJLQDVWKPDRUJ
+DWFKHU5$7UXVVHOO-1HOVRQ$/&DWHV:-U6WHZDUW).RZDO'HGLWRUV
&RQWUDFHSWLYH7HFKQRORJ\WKHGLWLRQ1HZ<RUN$UGHQW0HGLDD7DEOH

+DWFKHU5$7UXVVHOO-1HOVRQ$/&DWHV:-U6WHZDUW).RZDO'HGLWRUV
&RQWUDFHSWLYH7HFKQRORJ\WKHGLWLRQ1HZ<RUN$UGHQW0HGLDE
-DPHV/3HWDO3KDUPDFRNLQHWLFVRI$FHWDPLQRSKHQ3URWHLQ$GGXFWVLQ$GXOWVZLWK
$FHWDPLQRSKHQ2YHUGRVHDQG$FXWH/LYHU)DLOXUH'UXJ0HWDE'LVSRV

-XQLSHU()HWDO'HWHUPLQLQJDPLQLPDOLPSRUWDQWFKDQJHLQDGLVHDVHVSHFLILF4XDOLW\RI
/LIH4XHVWLRQQDLUH-&OLQ(SLGHPLRO-DQ
-XQLSHU()HWDO(YDOXDWLRQRILPSDLUPHQWRIKHDOWKUHODWHGTXDOLW\RIOLIHLQDVWKPD
GHYHORSPHQWRIDTXHVWLRQQDLUHIRUXVHLQFOLQLFDOWULDOV7KRUD[)HE
-XQLSHU()*X\DWW*+:LOOLDPV$*ULIILWK/(0HDVXULQJTXDOLW\RIOLIHLQDVWKPD$P
5HY5HVSLU'LV
-XQLSHU()$VWKPDTXDOLW\RIOLIHTXHVWLRQQDLUHV$4/4$4/46DQG 0LQL$4/4
%DFNJURXQGLQIRUPDWLRQDQGLQWHUYLHZLQJWLSV42/7HFKQRORJLHV,QF
.R]PD&0HWDO'HYHORSPHQWDQG9DOLGDWLRQRID3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH
4XHVWLRQQDLUHIRU,QKDODWLRQ'HYLFHV3$6$347UHDW5HVSLU0HG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
72
/H*DO)HWDO4XDQWLILFDWLRQRI+HSDWLWLV'HOWD9LUXV51$LQ6HUXPE\&RQVHQVXV
5HDO7LPH3&5,QGLFDWHV'LIIHUHQW3DWWHUQVRI9LURORJLFDO5HVSRQVHWR,QWHUIHURQ
7KHUDS\LQ&KURQLFDOO\,QIHFWHG3DWLHQWV-&OLQ0LFURELRO±
1DWKDQ5$6RUNQHVV&$.RVLQVNL0HWDO'HYHORSPHQWRIWKH$VWKPD&RQWURO7HVW$
VXUYH\IRUDVVHVVLQJDVWKPDFRQWURO-$OOHUJ\&OLQ,PPXQRO-DQXDU\
1,+$VWKPD*XLGHOLQHV6XPPDU\
KWWSZZZQKOELQLKJRYJXLGHOLQHVDVWKPDDVWKVXPPSGI
3HGHUVHQ62
%\UQH3$FRPSDULVRQRIHIILFDF\DQGVDIHW\RILQKDOHGFRUWLFRVWHURLGVLQ
DVWKPD$OOHUJ\
6FKDW]0HWDO7KHPLQLPDOO\LPSRUWDQWGLIIHUHQFHRIWKH$VWKPD&RQWURO7HVW7KH
-RXUQDORIDOOHUJ\DQGFOLQLFDOLPPXQRORJ\
7KH(XUR4RO*URXS7KH(XUR4RO*URXS(XUR4RO DQHZIDFLOLW\IRUWKH
PHDVXUHPHQWRIKHDOWKUHODWHGTXDOLW\RIOLIH+HDOWK3ROLF\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
73

$33(1',&(6

$SSHQGL[$EEUHYLDWLRQDQG7UDGHPDUNV
$&7
$VWKPD&RQWURO7HVW
$'5
$GYHUVH'UXJ5HDFWLRQ
$(
$GYHUVH(YHQW
$/7
$ODQLQH$PLQRWUDQVIHUDVH
$1&29$
$4/46
$QDO\VLVRI&RYDULDQFH
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH
$67
$VSDUWDWH$PLQRWUDQVIHUDVH
%,'
%8'
&
7ZLFHGDLO\
%XGHVRQLGH
&HOVLXV
&5)
&DVH5HFRUG)RUP
H&5)
(OHFWURQLF&DVH5HFRUG)RUP
&9
&DUGLRYDVFXODU
'1$
'HR[\ULERQXFOHLFDFLG
'3,
'U\3RZGHU,QKDOHU
)3
)OXWLFDVRQH3URSLRQDWH
(&*
(OHFWURFDUGLRJUDP
(3,
(SLGHPLRORJ\
(4'
)
(XUR4RO'
)RUPRWHURO
)'$
)(9
)RRGDQG'UXJ$GPLQLVWUDWLRQ
)RUFHGH[SLUDWRU\YROXPHLQRQHVHFRQG
))
)3
)OXWLFDVRQH)XURDWH
)OXWLFDVRQH3URSLRQDWH
)6+
)ROOLFOH6WLPXODWLQJ+RUPRQH
*&3
*RRG&OLQLFDO3UDFWLFH
*&63
*OREDO&OLQLFDO6DIHW\DQG3KDUPDFRYLJLODQFH
*,1$
*OREDO,QLWLDWLYHIRU$VWKPD
*3
*HQHUDO3UDFWLWLRQHU
*6.
*OD[R6PLWK.OLQH
+3$
+\SRWKDODPLFSLWXLWDU\D[LV
+/
+RGJHV/HKPDQQ
,%
,QYHVWLJDWRUV%URFKXUH
,&6
,QKDOHG&RUWLFRVWHURLG
,(&
,QGHSHQGHQW(WKLFV&RPPLWWHH
,J0
,PPXQRJOREXOLQ0
,J*
,PPXQRJOREXOLQ*
,15
,QWHUQDWLRQDO1RUPDOLVHG5DWLR
,3
,QYHVWLJDWLRQDO3URGXFW
,5%
,QVWLWXWLRQDO5HYLHZ%RDUG
,77
,QWHQWWR7UHDW
,9'
,Q9LWUR'LDJQRVWLF
,57
,QWHUDFWLYH5HVSRQVH7HFKQRORJ\
/$%$
/RQJ$FWLQJ%HWD$JRQLVW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
74
/'+
/DFWDWH'HK\GURJHQDVH
/6/9
0$56$
/DVW6XEMHFW/DVW9LVLW
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHLQ$VWKPD
TXHVWLRQQDLUH
0HG'5$
0FJ
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV
0LFURJUDP
0,
0XOWLSOHLPSXWDWLRQ
0,'
0LQLPDOO\,PSRUWDQW'LIIHUHQFH
0',
0HWHUHG'RVH,QKDOHU
0&,'
0LQLPDOO\&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
PO
0LOOLOLWUH
06'6
0DWHULDO6DIHW\'DWD6KHHW
0050
0L[HGHIIHFWVPRGHOZLWKUHSHDWHGPHDVXUHV
1'3,
1RYHO'U\3RZGHU,QKDOHU
3$6$34
3.
33
352
3DWLHQWV6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH
3KDUPDFRNLQHWLFV
3HUSURWRFRO
3DWLHQW5HSRUWHG2XWFRPHV
SJ
3LFRJUDP
SPRO
3LFRPROHV
4'
2QFH'DLO\
4R/
4XDOLW\RI/LIH
47F
&RUUHFWHG47LQWHUYDO
5$3
5HSRUWLQJ$QDO\VLV3ODQ
5(0/
51$
5HVWULFWHGPD[LPXPOLNHOLKRRG
5LERQXFOHLF$FLG
6
6$(
6DOPHWHURO
6HULRXV$GYHUVH(YHQW
6$3
6WDWLVWLFDO$QDO\VLV3ODQ
6'
62&
623
6WDQGDUGGHYLDWLRQ
6\VWHPRUJDQFODVV
6WDQGDUG2SHUDWLQJ3URFHGXUH
6P3&
6XPPDU\RI3URGXFW&KDUDFWHULVWLFV
6	3
6WDWLVWLFVDQG3URJUDPPLQJ
650
6WXG\5HIHUHQFH0DQXDO
8/1
8SSHU/LPLWRI1RUPDO
9,
9LODQWHURO
:+2
:RUOG+HDOWK2UJDQLVDWLRQ

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
75
Trademarks of the 
GlaxoSmithKline group of 
companies
Trademarks not owned by the GlaxoSmithKline 
group of companies
',6.86
$&7
(//,37$
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH $4/46
18&$/$
(4'
5(/9$5
0$56$TXHVWLRQQDLUH
6(5(7,'(
3$6$34XHVWLRQQDLUH
9,$1,
6\PELFRUW7XUEXKDOHU
785%2+$/(5
785%8+$/(5
;2/$,5
7XUEXKDOHUDQG7XUERKDOHUDUHERWKWUDGHQDPHV IRUWKHLQKDOHUGHYLFHXVHGIRU6\PELFRUW7KH\DUH XVHG
LQWHUFKDQJHDEO\LQWKLVGRFXPHQW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
76

$SSHQGL[
6WXG\6FKHPDWLF
))9,RSHQ ODEHORUXVXDODVWKPDPDLQWHQDQFHWUHDWPHQW
+=$VWXG\ GHVLJQ
9
'D\
5DQGRPLVDWLRQ
9
'D\
6FUHHQLQJ
ACT , MARS-A, 
AQLQ, EQ-5D, 
Spirometry
$VWKPD WUHDWHG ZLWK
,&60','3,Q 
Relvar 92/22 or 184/22 μg
ICS/LABA DPI on the market
Seretide®, Symbicort®
1-7 days
5
PRQWKV
ACT < 20
V2, errors ass-t:
• Read,
•Demonstration by HCP,
•1 dose,
•Errors asst & correction
9
:HHN 
9
:HHN 
Possibility to combine 
V1+V2= Day 0
9
3KRQHFDOO
:HHN 
9
3KRQHFDOO
:HHN 
V4, errors ass-t:
•1 dose,
•Errors asst
•Demonstration by 
HCP if critical errors
V6, errors ass-t:
•1 dose,
•Errors asst
•Demonstration by 
HCP if critical errors
ACT, safety
ACT, safety
ACT , MARS-A, 
PASAP, 
Spirometry
ACT , MARS-A, 
AQLQ, EQ-5D
$SKRQHFDOOLVSURYLGHGDW:HHNDQG:HHNLQRUGHUWRFKHFNZKHWKHUWKHVXEMHFW
KDVH[SHULHQFHGDQ\DGYHUVHHYHQWVDQGWKHQWKH,QYHVWLJDWRUFDOOLQJWKHSDWLHQWPXVW
GHWHUPLQHZKHWKHUWKHHYHQWLVUHODWHGWRVWXG\PHGLFDWLRQHLWKHUDUPDQGZKHWKHUWKH
HYHQWLVVHULRXV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
YLVLW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
77

$SSHQGL[4XHVWLRQQDLUHV
$VWKPD&RQWURO7HVW$&7
7KH$&7LVDYDOLGDWHGVHOIDGPLQLVWHUHGTXHVWLRQQDLUHXWLOLVLQJTXHVWLRQVWRDVVHVV
DVWKPDFRQWUROGXULQJWKHSDVW ZHHNVRQDSRLQWFDWHJRULFDOVFDOHWR%\
DQVZHULQJDOOTXHVWLRQVDVXEMHFWZLWKDVWKPDFDQREWDLQDVFRUHWKDWPD\UDQJH
EHWZHHQDQGZLWKKLJKHUVFRUHVLQGLFDWLQJEHWWHUFRQWURO$Q$&7VFRUHRIWR
VXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLVXQOLNHO\WREHZHOOFRQWUROOHG$VFRUHRIWR
VXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLVOLNHO\WREHZHOOFRQWUROOHG7KHWRWDOVFRUHLV
FDOFXODWHGDVWKHVXPRIWKHVFRUHVIURPDOOTXHVWLRQV>1DWKDQ@7KHPLQLPDOO\
LPSRUWDQWGLIIHUHQFH0,'IRU$&7LV>6FKDW]@
6XEMHFWVZLOOFRPSOHWHWKH$&7DW6FUHHQLQJ9LVLWDW5DQGRPLVDWLRQ9LVLWDW
:HHN9LVLWDQGDW:HHN9LVLWRQVLWH7ZRWHOHSKRQHFDOOVDUHSURYLGHGDW
:HHNDQGDQGVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&7TXHVWLRQQDLUH
DQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
7KH$&7KDVEHHQGHYHORSHGDVDPHDVXUHRIVXEMHFWV¶DVWKPDFRQWUROWKDWFDQEH
TXLFNO\DQGHDVLO\FRPSOHWHGLQFOLQLFDOSUDFWLFH7KHTXHVWLRQVDUHGHVLJQHGWREHVHOI
FRPSOHWHGE\WKHVXEMHFW,WLVUHFRPPHQGHGWKDWWKH$&7EHDGPLQLVWHUHGDWWKHVDPH
WLPHGXULQJHDFKYLVLW7KH$&7VKRXOGEHFRPSOHWHGEHIRUHDQ\SURFHGXUHVDUH
SHUIRUPHGRQWKHVXEMHFWWRDYRLGLQIOXHQFLQJWKHVXEMHFW¶VUHVSRQVH$GHTXDWHWLPH
VKRXOGEHDOORZHGWRFRPSOHWHDOOLWHPVRQWKH$&7
7KHVXEMHFWVKRXOGFRPSOHWHWKHTXHVWLRQQDLUHLQDTXLHWDUHD
7KH,QYHVWLJDWRUVKRXOGDVNWKHVXEMHFWWRFRPSOHWHWKHTXHVWLRQVDVDFFXUDWHO\DV
SRVVLEOH,IWKHVXEMHFWUHTXHVWVKHOSRUFODULILFDWLRQZLWKDQ\RIWKHTXHVWLRQVKHVKHZLOO
EHDVNHGWRUHUHDGWKHLQVWUXFWLRQVDQGJLYHWKHDQVZHUWKDWEHVWUHIOHFWVKRZKHVKHIHOW
RYHUWKHSUHYLRXVZHHNV7KHVXEMHFWVKRXOGEHUHDVVXUHGWKDWWKHUH DUHQRULJKWRU
ZURQJDQVZHUV7KH,QYHVWLJDWRUVKRXOGQRWSURYLGHWKHVXEMHFWZLWKDQ\DQVZHURU
DWWHPSWWRLQWHUSUHWDQ\SRUWLRQRIDTXHVWLRQ
3OHDVHUHIHUWRWKH6WXG\5HIHUHQFH0DQXDO650IRUIXUWKHUGHWDLOV
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH$4/46
7KH$4/46LVDPRGLILHGYHUVLRQRIWKHRULJLQDO$4/4LQZKLFKDOOWKHDFWLYLW\
TXHVWLRQVDUHJHQHULFDQGLWKDVEHHQYDOLGDWHGIRUXVHLQDVWKPDVXEMHFWVEHWZHHQWKH
DJHVRIDQG7KH$4/4LVDGLVHDVHVSHFLILFVHOIDGPLQLVWHUHGTXDOLW\RIOLIH
TXHVWLRQQDLUHGHYHORSHGWRHYDOXDWHWKHLPSDFWRIDVWKPDWUHDWPHQWVRQWKHTXDOLW\RIOLIH
RIDVWKPDVXIIHUHUVRYHUWKHODVWZHHNV>-XQLSHU@$4/46ZLOOEHPHDVXUHGDW
5DQGRPLVDWLRQDQGDW:HHN(DUO\:LWKGUDZDOYLVLW
7KH$4/4ZKLFKLVDYDLODEOHLQQXPHURXVODQJXDJHVKDVDGHPRQVWUDWHGYDOLGLW\
UHOLDELOLW\DQGUHSURGXFLELOLW\>-XQLSHU-XQLSHU@7KH$4/4FRQWDLQV
LWHPVLQIRXUGRPDLQVDFWLYLW\OLPLWDWLRQLWHPVV\PSWRPVLWHPVHPRWLRQDO
IXQFWLRQLWHPVDQGHQYLURQPHQWDOVWLPXOLLWHPV,QDGGLWLRQWKHLWHPVRIWKH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
78
TXHVWLRQQDLUHDUHDOVRDYHUDJHGWRSURGXFHDQRYHUDOOTXDOLW\RIOLIHVFRUH7KHUHVSRQVH
IRUPDWFRQVLVWVRIDVHYHQSRLQWVFDOHZKHUHDYDOXHRILQGLFDWHV³WRWDOLPSDLUPHQW´DQG
LQGLFDWHV³QRLPSDLUPHQW´$VVXPLQJDVWDWLVWLFDOO\VLJQLILFDQWUHVXOWSWKH
PLQLPDOFOLQLFDOO\PHDQLQJIXOFKDQJHLQRYHUDOOTXDOLW\RIOLIHRULQTXDOLW\RIOLIHIRU
DQ\RIWKHLQGLYLGXDOGRPDLQVLVSRLQWV>-XQLSHU@
,WLVUHFRPPHQGHGWKDWWKH$4/46EHDGPLQLVWHUHGDWWKHVDPHWLPHGXULQJHDFKYLVLW
7KH$4/46PXVWEHDGPLQLVWHUHGEHIRUHLQTXLULQJDERXW$(VDQGDQ\VWXG\
DVVHVVPHQWV$GHTXDWHWLPHVKRXOGEHDOORZHGWRFRPSOHWHDOOLWHPVRQWKH$4/46
1RVWDWHGRULPSOLHGWLPHIRUFRPSOHWLQJWKH$4/46ZLOOEHJLYHQWKRXJKWKHVXUYH\
W\SLFDOO\WDNHVWRPLQXWHVWRFRPSOHWH
6XEMHFWVVKRXOGFRPSOHWHDOOWKHTXHVWLRQVIURPWKH$4/467KH,QYHVWLJDWRUZLOODVN
WKHVXEMHFWWRFRPSOHWHDOOTXHVWLRQVDVDFFXUDWHO\DVSRVVLEOH,IWKHVXEMHFWUHTXHVWVKHOS
RUFODULILFDWLRQRIDQ\TXHVWLRQLQWKH$4/46KHRUVKHVKRXOGEHDVNHGWRUHUHDGWKH
LQVWUXFWLRQVDQGJLYHWKHDQVZHUWKDWEHVWUHIOHFWVKRZKHVKHIHHOVRYHUWKHSUHYLRXVWZR
ZHHNV7KHVXEMHFWVKRXOGEHUHDVVXUHGWKDWWKHUHDUHQRULJKWRUZURQJDQVZHUV7KH
,QYHVWLJDWRUZLOOQRWSURYLGHWKHVXEMHFWZLWKDQ\DQVZHU RUDWWHPSWWRLQWHUSUHWDQ\
SRUWLRQRIDTXHVWLRQ3OHDVHUHIHUWRWKH6WXG\5HIHUHQFH0DQXDO 650 IRUIXUWKHU
GHWDLOV
(XUR4RO4XHVWLRQQDLUH(4'/HYHO
*HQHUDOKHDOWKVWDWXVZLOOEHDVVHVVHGZLWKWKH(XUR4RO(4'/HYHO4XHVWLRQQDLUH
DW5DQGRPLVDWLRQDQG:HHN(DUO\:LWKGUDZDOYLVLW
7KH(4'LVDVWDQGDUGLVHGLQVWUXPHQWIRUXVHDVDPHDVXUHRIKHDOWKVWDWXVWKDWDVNV
VXEMHFWVTXHVWLRQVDERXWWKHLUKHDOWKVWDWXV³WRGD\´>7KH(XUR4RO*URXS@,WLV
GHVLJQHGIRUVHOIFRPSOHWLRQDQGLVFRJQLWLYHO\VLPSOH7KH(4'LVDWZRSDUWVHOI
DVVHVVPHQWTXHVWLRQQDLUH7KHILUVWSDUWFRQVLVWVRIILYHLWHPVFRYHULQJILYHGLPHQVLRQV
PRELOLW\VHOIFDUHXVXDODFWLYLWLHVSDLQGLVFRPIRUWDQGDQ[LHW\GHSUHVVLRQ(DFK
GLPHQVLRQLVPHDVXUHGE\DWKUHHSRLQW/LNHUWVFDOHQRSUREOHPVRPHPRGHUDWH
SUREOHP>V@DQGXQDEOHH[WUHPHSUREOHP>V@
5HVSRQGHQWVDUHDVNHGWRFKRRVHRQHOHYHOWKDWUHIOHFWVWKHLURZQKHDOWKVWDWHWRGD\IRU
HDFKRIWKHILYHGLPHQVLRQV5HVSRQGHQWVFDQWKHQEHFODVVLILHGLQWRRQHRIGLVWLQFW
KHDOWKVWDWHV(4'KHDOWKVWDWHVFDQEHFRQYHUWHGWRDVLQJOHVXPPDU\LQGH[E\
DSSO\LQJDIRUPXODWKDWDWWDFKHVZHLJKWVWRHDFKRIWKHOHYHOVLQHDFKGLPHQVLRQ7KH
IRUPXODLVEDVHGRQWKHYDOXDWLRQRI(4'KHDOWKVWDWHVIURPJHQHUDOSRSXODWLRQ
VDPSOHV>'RODQ@
7KHVHFRQGSDUWRIWKHTXHVWLRQQDLUHFRQVLVWVRIDYHUWLFDOYLVXDODQDORJXHVFDOH(4'
9$6WKDWKDVHQGSRLQWVRI7KHEHVWKHDOWK\RXFDQLPDJLQHDQFKRUHGDWDQG
7KHZRUVWKHDOWK\RXFDQLPDJLQHDQFKRUHGDW5HVSRQGHQWVDUHDVNHGWRLQGLFDWH
KRZWKH\UDWHWKHLUFXUUHQWKHDOWKVWDWHE\GUDZLQJDOLQHIURPWKHER[PDUNHG³\RXUKHDOWK
VWDWXVWRGD\´WRWKHDSSURSULDWHSRLQWRQWKH(4'9$6VFDOH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
79
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH(4'DWWKHVDPHWLPHDWWKH
VSHFLILHG YLVLWV DQG EHIRUH DQ\ VWXG\ SURFHGXUHV 7KH (4' ZLOO EH DGPLQLVWHUHG DW
5DQGRPLVDWLRQ9LVLWDQG:HHN9LVLW(DUO\:LWKGUDZDOYLVLW
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$
6XEMHFWVHOIUHSRUWHGDGKHUHQFHWRPHGLFDWLRQZLOOEHDVVHVVHGZLWKWKH0HGLFDWLRQ
$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDW9LVLW9LVLWDQG9LVLW
(DUO\:LWKGUDZDO YLVLW
7KH0$56$LVDLWHPTXHVWLRQQDLUHZKHUHPHGLFDWLRQXVHLVUDWHGRQDSRLQW/LNHUW
VFDOHLQGLFDWLQJµDOZD\V¶WRLQGLFDWLQJµQHYHU¶,WKDVEHHQYDOLGDWHGDVDVHOIUHSRUWHG
PHDVXUHRIDGKHUHQFHZLWK,&6IRUVXEMHFWVZLWKDVWKPDDQGLQFOXGHVJHQHULF³,XVHLW
UHJXODUO\HYHU\GD\´DQGOXQJFRQGLWLRQVSHFLILFTXHVWLRQVDERXWPHGLFDWLRQXVH³,RQO\XVH
LWZKHQ,IHHOEUHDWKOHVV´>&RKHQ@7KHUHLVQRVSHFLILHGWLPHIUDPHRQZKLFK
UHVSRQVHVVKRXOG EHEDVHG
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH0$56$DWWKHVDPHWLPHDWWKH
VSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH0$56KDYHQRVSHFLILHGWLPHIUDPHRQ
ZKLFKUHVSRQVHVVKRXOGEHEDVHG
3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH3$6$34
7KH3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH3$6$34>.R]PD@LVD
PXOWLLWHPPHDVXUHRIUHVSLUDWRU\LQKDODWLRQGHYLFHVDWLVIDFWLRQDQGSUHIHUHQFHGHVLJQHG
WREHHDVLO\XQGHUVWRRGDQGDGPLQLVWHUHGWRSDWLHQWVZLWKDVWKPDDQG&23'3DWLHQW
VDWLVIDFWLRQZLWKHDFKGHYLFHDQGGHYLFHSUHIHUHQFHZLOOEHDVVHVVHGDW9LVLW(DUO\
:LWKGUDZDOYLVLW
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH3$6$34DWWKHVDPHWLPHDWWKH
VSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH3$6$34KDVQRVSHFLILHGWLPHIUDPH
RQZKLFKUHVSRQVHVVKRXOGEHEDVHG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
80

$SSHQGL[/LYHU&KHPLVWU\6WRSSLQJDQG)ROORZXS
&ULWHULD
3KDVH,,,,9OLYHUFKHPLVWU\VWRSSLQJDQGLQFUHDVHGPRQLWRULQJFULWHULD KDYHEHHQ
GHVLJQHGWRDVVXUHVXEMHFWVDIHW\DQGHYDOXDWHOLYHUHYHQWHWLRORJ\LQDOLJQPHQWZLWKWKH
)'$SUHPDUNHWLQJFOLQLFDOOLYHUVDIHW\JXLGDQFH
KWWSZZZIGDJRYGRZQORDGV'UXJV*XLGDQFH&RPSOLDQFH5HJXODWRU\,QIRUPDWLRQ*XLG
DQFHV8&0SGI
3KDVH,,,,9OLYHUFKHPLVWU\VWRSSLQJFULWHULDDQGUHTXLUHGIROORZXSDVVHVVPHQWV
Liver Chemistry Stopping Criteria - Liver Stopping Event
ALT-absolute
$/7∀[8/1
ALT Increase
$/7∀[8/1EXW[8/1SHUVLVWVIRU∀ZHHNV
$/7∀[8/1EXW[8/1SHUVLVWVIRU∀ZHHNV
Bilirubin1, 2
$/7∀[8/1and ELOLUXELQ∀[8/1!GLUHFWELOLUXELQ
INR2
$/7∀[8/1and ,15!LI,15PHDVXUHG
Cannot 
Monitor
$/7∀[8/1EXW[8/1DQGFDQQRWEHPRQLWRUHGZHHNO\IRU∀ZHHNV
$/7∀[8/1EXW[8/1DQGFDQQRWEHPRQLWRUHGZHHNO\IRU∀ZHHNV
Symptomatic3
$/7∀[8/1DVVRFLDWHGZLWKV\PSWRPVQHZRUZRUVHQLQJEHOLHYHGWREH
UHODWHGWROLYHULQMXU\RUK\SHUVHQVLWLYLW\
Required Actions and Follow up Assessments following ANY Liver Stopping Event
Actions
Follow Up Assessments
!
,PPHGLDWHO\GLVFRQWLQXHVWXG\WUHDWPHQW
!
5HSRUWWKHHYHQWWR*6. within 24 hours
!
&RPSOHWHWKHOLYHUHYHQW&5)DQGFRPSOHWH
DQ6$(GDWDFROOHFWLRQWRROLIWKHHYHQWDOVR
PHHWVWKHFULWHULDIRUDQ6$(2
!
3HUIRUPOLYHUHYHQWIROORZXSDVVHVVPHQWV
!
0RQLWRUWKHVXEMHFWXQWLOOLYHUFKHPLVWULHV
UHVROYHVWDELOL]HRUUHWXUQWRZLWKLQEDVHOLQH
VHHMONITORING EHORZ
!
Do not restart/rechallenge VXEMHFWZLWK
VWXG\WUHDWPHQWXQOHVVDOORZHGSHUSURWRFRO
DQG*6.0HGLFDO*RYHUQDQFHDSSURYDOis 
!
9LUDOKHSDWLWLVVHURORJ\
!
2QO\LQWKRVHZLWKXQGHUO\LQJFKURQLF
KHSDWLWLV%DWVWXG\HQWU\LGHQWLILHGE\
SRVLWLYHKHSDWLWLV%VXUIDFHDQWLJHQ
TXDQWLWDWLYHKHSDWLWLV%'1$DQGKHSDWLWLV
GHOWDDQWLERG\
!
%ORRGVDPSOHIRUSKDUPDFRNLQHWLF3.
DQDO\VLVREWDLQHGZLWKLQDIWHUODVWGRVH
!
6HUXPFUHDWLQHSKRVSKRNLQDVH&3.DQG
ODFWDWHGHK\GURJHQDVH/'+
!
)UDFWLRQDWHELOLUXELQLIWRWDO
ELOLUXELQ∀[8/1

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
81
granted UHIHUWR$SSHQGL[
!
,IUHVWDUWUHFKDOOHQJHnot  allowed or not 
grantedSHUPDQHQWO\GLVFRQWLQXHVWXG\
WUHDWPHQWDQGPD\FRQWLQXHVXEMHFWLQWKH
VWXG\IRUDQ\SURWRFROVSHFLILHGIROORZXS
DVVHVVPHQWV
MONITORING:
For bilirubin or INR criteria:
!
5HSHDWOLYHUFKHPLVWULHVLQFOXGH$/7$67
DONDOLQHSKRVSKDWDVHELOLUXELQ DQGSHUIRUP
OLYHUHYHQWIROORZXSDVVHVVPHQWVZLWKLQ24 
hrs
!
0RQLWRUVXEMHFWVWZLFHZHHNO\XQWLOOLYHU
FKHPLVWULHVUHVROYHVWDELOL]HRUUHWXUQWR
ZLWKLQEDVHOLQH
!
$VSHFLDOLVWRUKHSDWRORJ\FRQVXOWDWLRQLV
UHFRPPHQGHG
For All other criteria:
!
5HSHDWOLYHUFKHPLVWULHVLQFOXGH$/7$67
DONDOLQHSKRVSKDWDVHELOLUXELQ DQGSHUIRUP
OLYHUHYHQWIROORZXSDVVHVVPHQWVZLWKLQ24-
72 hrs 
!
0RQLWRUVXEMHFWVZHHNO\XQWLOOLYHUFKHPLVWULHV
UHVROYHVWDELOL]HRUUHWXUQWRZLWKLQEDVHOLQH
!
2EWDLQFRPSOHWHEORRGFRXQWZLWK
GLIIHUHQWLDOWRDVVHVVHRVLQRSKLOLD
!
5HFRUGWKHDSSHDUDQFHRUZRUVHQLQJRI
FOLQLFDOV\PSWRPVRIOLYHULQMXU\RU
K\SHUVHQVLWLYLW\RQWKH$(UHSRUWIRUP
!
5HFRUGXVHRIFRQFRPLWDQWPHGLFDWLRQVRQ
WKHFRQFRPLWDQWPHGLFDWLRQVUHSRUWIRUP
LQFOXGLQJDFHWDPLQRSKHQKHUEDO
UHPHGLHVRWKHURYHUWKHFRXQWHU
PHGLFDWLRQV
!
5HFRUGDOFRKROXVHRQWKHOLYHUHYHQW
DOFRKROLQWDNHFDVHUHSRUWIRUP
For bilirubin or INR criteria:
!
$QWLQXFOHDUDQWLERG\DQWLVPRRWKPXVFOH
DQWLERG\7\SHDQWLOLYHUNLGQH\
PLFURVRPDODQWLERGLHVDQGTXDQWLWDWLYH
WRWDOLPPXQRJOREXOLQ*,J*RUJDPPD
JOREXOLQV
!
6HUXPDFHWDPLQRSKHQDGGXFW+3/&
DVVD\TXDQWLILHVSRWHQWLDODFHWDPLQRSKHQ
FRQWULEXWLRQWROLYHULQMXU\LQVXEMHFWVZLWK
GHILQLWHRUOLNHO\DFHWDPLQRSKHQXVHLQWKH
SUHFHGLQJZHHN>-DPHV@NOTE: 
not required in China
!
/LYHULPDJLQJXOWUDVRXQGPDJQHWLF
UHVRQDQFHRUFRPSXWHULVHGWRPRJUDSK\
DQGRUOLYHUELRSV\WRHYDOXDWHOLYHU
GLVHDVHFRPSOHWH/LYHU,PDJLQJDQGRU
/LYHU%LRSV\&5)IRUPV

6HUXPELOLUXELQIUDFWLRQDWLRQVKRXOGEHSHUIRUPHGLIWHVWLQJLVDYDLODEOH,IVHUXPELOLUXELQIUDFWLRQDWLRQLVQRW
LPPHGLDWHO\DYDLODEOHGLVFRQWLQXHVWXG\WUHDWPHQWIRUWKDWVXEMHFWLI$/7∀[8/1and ELOLUXELQ∀[8/1
$GGLWLRQDOO\LIVHUXPELOLUXELQIUDFWLRQDWLRQWHVWLQJLVXQDYDLODEOHrecord presence of detectable urinary 
bilirubin on dipstickLQGLFDWLQJGLUHFWELOLUXELQHOHYDWLRQVDQGVXJJHVWLQJOLYHULQMXU\

$OOHYHQWVRI$/7∀[8/1and ELOLUXELQ∀[8/1!GLUHFWELOLUXELQRU$/7∀[8/1and ,15!LI,15
PHDVXUHGZKLFKPD\LQGLFDWHVHYHUHOLYHULQMXU\SRVVLEOHµ+\¶V/DZ¶must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis),15PHDVXUHPHQWLVQRWUHTXLUHGDQGWKHWKUHVKROGYDOXHVWDWHG
ZLOOQRWDSSO\WRVXEMHFWVUHFHLYLQJDQWLFRDJXODQWV

1HZRUZRUVHQLQJV\PSWRPVEHOLHYHGWREHUHODWHGWROLYHULQMXU\VXFKDVIDWLJXHQDXVHDYRPLWLQJULJKWXSSHU
TXDGUDQWSDLQRUWHQGHUQHVVRUMDXQGLFHRUEHOLHYHGWREHUHODWHGWRK\SHUVHQVLWLYLW\VXFKDVIHYHUUDVKRU
HRVLQRSKLOLD

+HSDWLWLV$,J0DQWLERG\+HSDWLWLV%VXUIDFHDQWLJHQDQG+HSDWLWLV%&RUH$QWLERG\,J0+HSDWLWLV&51$
&\WRPHJDORYLUXV,J0DQWLERG\(SVWHLQ%DUUYLUDOFDSVLGDQWLJHQ,J0DQWLERG\RULIXQDYDLODEOHREWDLQ
KHWHURSKLOHDQWLERG\RUPRQRVSRWWHVWLQJ+HSDWLWLV(,J0DQWLERG\

,IKHSDWLWLVGHOWDDQWLERG\DVVD\FDQQRWEHSHUIRUPHGLWFDQEHUHSODFHGZLWKD3&5RIKHSDWLWLV'51$YLUXV
ZKHUHQHHGHG>/H*DO@

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
82

3.VDPSOHPD\QRWEHUHTXLUHGIRUVXEMHFWVNQRZQWREHUHFHLYLQJSODFHERRUQRQ*6.FRPSDUDWRUWUHDWPHQWV
5HFRUGWKHGDWHWLPHRIWKH3.EORRGVDPSOHGUDZDQGWKHGDWHWLPHRIWKHODVWGRVHRIVWXG\WUHDWPHQWSULRUWR
EORRGVDPSOHGUDZRQWKH&5),IWKHGDWHRUWLPHRIWKHODVWGRVHLVXQFOHDUSURYLGHWKHVXEMHFW¶VEHVW
DSSUR[LPDWLRQ,IWKHGDWHWLPHRIWKHODVWGRVHFDQQRWEHDSSUR[LPDWHG25D3.VDPSOHFDQQRWEHFROOHFWHGLQ
WKHWLPHSHULRGLQGLFDWHGDERYHGRQRWREWDLQD3.VDPSOH,QVWUXFWLRQVIRUVDPSOHKDQGOLQJDQGVKLSSLQJDUHLQ
WKH650
3KDVH,,,,9OLYHUFKHPLVWU\LQFUHDVHGPRQLWRULQJFULWHULDZLWKFRQWLQXHGWKHUDS\
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event
Criteria
Actions
$/7∀[8/1DQG [8/1and
ELOLUXELQ[8/1without V\PSWRPV
EHOLHYHGWREHUHODWHGWROLYHULQMXU\RU
K\SHUVHQVLWLYLW\and ZKRFDQEH
PRQLWRUHGZHHNO\IRUZHHNV
25
$/7∀[8/1DQG[8/1and
ELOLUXELQ[8/1without V\PSWRPV
EHOLHYHGWREHUHODWHGWROLYHULQMXU\RU
K\SHUVHQVLWLYLW\and ZKRFDQEH
PRQLWRUHGZHHNO\IRUZHHNV
!
1RWLI\WKH*6.PHGLFDOPRQLWRUwithin 24 hours
RIOHDUQLQJRIWKHDEQRUPDOLW\WRGLVFXVVVXEMHFW
VDIHW\
!
6XEMHFWFDQFRQWLQXHVWXG\WUHDWPHQW
!
6XEMHFWPXVWUHWXUQZHHNO\IRUUHSHDWOLYHU
FKHPLVWULHV$/7$67DONDOLQHSKRVSKDWDVH
ELOLUXELQXQWLO WKH\UHVROYHVWDELOLVHRUUHWXUQWR
ZLWKLQEDVHOLQH
!
,IDWDQ\WLPHVXEMHFWPHHWVWKHOLYHUFKHPLVWU\
VWRSSLQJFULWHULDSURFHHGDVGHVFULEHGDERYH
!
,I$/7GHFUHDVHVIURP$/7∀[8/1DQG [8/1
WR[8/1EXW[8/1FRQWLQXHWRPRQLWRUOLYHU
FKHPLVWULHVZHHNO\
!
,IDIWHUZHHNVRIPRQLWRULQJ$/7[8/1DQG
ELOLUXELQ[8/1PRQLWRUVXEMHFWVWZLFHPRQWKO\
XQWLOOLYHUFKHPLVWULHVQRUPDOL]HRUUHWXUQWRZLWKLQ
EDVHOLQH
5HIHUHQFHV
-DPHV/3/HW]LJ/6LPSVRQ30&DSSDUHOOL(5REHUWV':+LQVRQ-$'DYHUQ7-/HH
:03KDUPDFRNLQHWLFVRI$FHWDPLQRSKHQ$GGXFWLQ$GXOWVZLWK$FHWDPLQRSKHQ
2YHUGRVHDQG$FXWH/LYHU)DLOXUH'UXJ0HWDE'LVSRV
/H*DO)*RUGLHQ($IIRODEL' +DQVOLN7$OORXL&'pQ\3*DXOW(4XDQWLILFDWLRQ
RI+HSDWLWLV'HOWD9LUXV51$LQ6HUXPE\&RQVHQVXV5HDO7LPH3&5,QGLFDWHV
'LIIHUHQW3DWWHUQVRI9LURORJLFDO5HVSRQVHWR,QWHUIHURQ7KHUDS\LQ&KURQLFDOO\,QIHFWHG
3DWLHQWV-&OLQ0LFURELRO±

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
83

$SSHQGL['HILQLWLRQRIDQG3URFHGXUHVIRU5HFRUGLQJ
(YDOXDWLQJ)ROORZ8SDQG5HSRUWLQJRI$GYHUVH(YHQWV

'HILQLWLRQRI$GYHUVH(YHQWVDQG$'5V
$GYHUVH(YHQWDQG$'5V'HILQLWLRQ
$Q$(LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHLQDSDWLHQWRUFOLQLFDOLQYHVWLJDWLRQVXEMHFW
WHPSRUDOO\DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOSURGXFWZKHWKHURUQRWFRQVLGHUHG
UHODWHGWRWKHPHGLFLQDOSURGXFW
7KHGHILQLWLRQRIDQ$'5LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHLQDSDWLHQWRUFOLQLFDO
LQYHVWLJDWLRQVXEMHFWWHPSRUDOO\DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOSURGXFWIRU
ZKLFKWKHUHLVDUHDVRQDEOHSRVVLELOLW\WKDWWKHXQWRZDUGRFFXUUHQFHLVFDXVDOO\UHODWHGWR
WKHPHGLFLQDOSURGXFW$'5VDUHDVXEVHWRI$(VIRUDJLYHQPHGLFLQDOSURGXFW
127($Q$(FDQWKHUHIRUHEHDQ\ XQIDYRUDEOH DQGXQLQWHQGHGVLJQLQFOXGLQJDQ
DEQRUPDOODERUDWRU\ILQGLQJV\PSWRPRUGLVHDVHQHZRUH[DFHUEDWHGWHPSRUDOO\
DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOSURGXFW
(YHQWVPHHWLQJ $(GHILQLWLRQLQFOXGH
$Q\DEQRUPDOODERUDWRU\WHVWUHVXOWVKHPDWRORJ\FOLQLFDOFKHPLVWU\RUXULQDO\VLVRU
RWKHUVDIHW\DVVHVVPHQWVHJ(&*VUDGLRORJLFDOVFDQVYLWDOVLJQVPHDVXUHPHQWV
LQFOXGLQJWKRVHWKDWZRUVHQIURPEDVHOLQHDQGIHOWWREHFOLQLFDOO\VLJQLILFDQWLQWKH
PHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKHLQYHVWLJDWRU
([DFHUEDWLRQRIDFKURQLFRULQWHUPLWWHQWSUHH[LVWLQJFRQGLWLRQLQFOXGLQJHLWKHUDQ
LQFUHDVHLQIUHTXHQF\DQGRULQWHQVLW\RIWKHFRQGLWLRQ
1HZFRQGLWLRQVGHWHFWHGRUGLDJQRVHGDIWHUVWXG\WUHDWPHQWDGPLQLVWUDWLRQHYHQWKRXJKLW
PD\KDYHEHHQSUHVHQWSULRUWRWKHVWDUWRIWKHVWXG\
6LJQVV\PSWRPVRUWKHFOLQLFDOVHTXHODHRIDVXVSHFWHGLQWHUDFWLRQ
6LJQVV\PSWRPVRUWKHFOLQLFDOVHTXHODHRIDVXVSHFWHGRYHUGRVHRIHLWKHUVWXG\
WUHDWPHQWRUDFRQFRPLWDQWPHGLFDWLRQ RYHUGRVHSHUVHZLOOQRWEHUHSRUWHGDVDQ
$(6$(XQOHVVWKLVLVDQLQWHQWLRQDORYHUGRVHWDNHQZLWKSRVVLEOHVXLFLGDOVHOIKDUPLQJ
LQWHQW7KLVVKRXOGEHUHSRUWHGUHJDUGOHVVRIVHTXHODH
/DFNRIHIILFDF\RUIDLOXUHRIH[SHFWHGSKDUPDFRORJLFDODFWLRQSHUVHZLOOQRWEH
UHSRUWHGDVDQ$(RU6$(+RZHYHUWKHVLJQVDQGV\PSWRPVDQGRUFOLQLFDOVHTXHODH
UHVXOWLQJIURPODFNRIHIILFDF\ZLOOEHUHSRUWHGLIWKH\IXOILOWKHGHILQLWLRQRIDQ$(RU
6$(

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
84
(YHQWV127 PHHWLQJGHILQLWLRQRIDQ$(LQFOXGH
$Q\ FOLQLFDOO\VLJQLILFDQWDEQRUPDOODERUDWRU\ILQGLQJVRURWKHUDEQRUPDOVDIHW\
DVVHVVPHQWVZKLFKDUHDVVRFLDWHGZLWKWKHXQGHUO\LQJGLVHDVHXQOHVVMXGJHGE\WKH
LQYHVWLJDWRUWREHPRUHVHYHUHWKDQH[SHFWHGIRUWKHVXEMHFW¶VFRQGLWLRQ
7KHGLVHDVHGLVRUGHUEHLQJVWXGLHGRUH[SHFWHGSURJUHVVLRQVLJQVRUV\PSWRPVRIWKH
GLVHDVHGLVRUGHUEHLQJVWXGLHGXQOHVVPRUHVHYHUHWKDQH[SHFWHGIRUWKHVXEMHFW¶V
FRQGLWLRQ
0HGLFDORUVXUJLFDOSURFHGXUHHJHQGRVFRS\DSSHQGHFWRP\WKHFRQGLWLRQWKDWOHDGV
WRWKHSURFHGXUHLVDQ$(
6LWXDWLRQVZKHUHDQXQWRZDUGPHGLFDORFFXUUHQFHGLGQRWRFFXUVRFLDODQGRU
FRQYHQLHQFHDGPLVVLRQWRDKRVSLWDO
$QWLFLSDWHGGD\WRGD\IOXFWXDWLRQVRISUHH[LVWLQJGLVHDVHVRUFRQGLWLRQVSUHVHQWRU
GHWHFWHGDWWKHVWDUWRIWKHVWXG\WKDWGRQRWZRUVHQ

'HILQLWLRQRI6HULRXV$GYHUVH(YHQWV
,IDQHYHQWLVQRWDQ$(SHUGHILQLWLRQDERYHWKHQLWFDQQRWEHDQ6$(HYHQLIVHULRXV
FRQGLWLRQVDUHPHWHJKRVSLWDOL]DWLRQIRUVLJQVV\PSWRPVRIWKHGLVHDVHXQGHUVWXG\
GHDWKGXHWRSURJUHVVLRQRIGLVHDVHHWF
6HULRXV$GYHUVH(YHQW6$(LVGHILQHGDVDQ\XQWRZDUGPHGLFDORFFXUUHQFHWKDW
DWDQ\GRVH
D 5HVXOWVLQGHDWK
E ,VOLIHWKUHDWHQLQJ
127(
7KHWHUP
OLIHWKUHDWHQLQJ
LQWKHGHILQLWLRQRI
VHULRXV
UHIHUVWRDQHYHQWLQZKLFKWKH
VXEMHFWZDVDWULVNRIGHDWKDWWKHWLPHRIWKHHYHQW,WGRHVQRWUHIHUWRDQHYHQWZKLFK
K\SRWKHWLFDOO\PLJKWKDYHFDXVHGGHDWKLILWZHUHPRUHVHYHUH
F 5HTXLUHVKRVSLWDOL]DWLRQRUSURORQJDWLRQRIH[LVWLQJKRVSLWDOL]DWLRQ
127(
,QJHQHUDOKRVSLWDOL]DWLRQVLJQLILHVWKDWWKHVXEMHFWKDVEHHQGHWDLQHGXVXDOO\LQYROYLQJ
DWOHDVWDQRYHUQLJKWVWD\DWWKHKRVSLWDORUHPHUJHQF\ZDUGIRUREVHUYDWLRQDQGRU
WUHDWPHQWWKDWZRXOGQRWKDYHEHHQDSSURSULDWHLQWKHSK\VLFLDQ¶VRIILFHRURXWSDWLHQW
VHWWLQJ&RPSOLFDWLRQVWKDWRFFXUGXULQJKRVSLWDOL]DWLRQDUH$(V,IDFRPSOLFDWLRQ
SURORQJVKRVSLWDOL]DWLRQRU IXOILOOV DQ\RWKHUVHULRXVFULWHULDWKHHYHQWLVVHULRXV:KHQ
LQGRXEWDVWRZKHWKHU³KRVSLWDOL]DWLRQ´RFFXUUHGRUZDVQHFHVVDU\WKH$(VKRXOGEH
FRQVLGHUHGVHULRXV
+RVSLWDOL]DWLRQIRUHOHFWLYHWUHDWPHQWRIDSUHH[LVWLQJFRQGLWLRQWKDWGLGQRWZRUVHQIURP

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
85
EDVHOLQHLVQRWFRQVLGHUHGDQ$(
G 5HVXOWVLQGLVDELOLW\LQFDSDFLW\
127(
7KHWHUPGLVDELOLW\PHDQVDVXEVWDQWLDOGLVUXSWLRQRIDSHUVRQ¶VDELOLW\WRFRQGXFWQRUPDO
OLIHIXQFWLRQV
7KLVGHILQLWLRQLVQRWLQWHQGHGWRLQFOXGHH[SHULHQFHVRIUHODWLYHO\PLQRUPHGLFDO
VLJQLILFDQFHVXFKDVXQFRPSOLFDWHGKHDGDFKHQDXVHDYRPLWLQJ GLDUUKHDLQIOXHQ]DDQG
DFFLGHQWDOWUDXPDHJVSUDLQHGDQNOHZKLFKPD\LQWHUIHUHRUSUHYHQWHYHU\GD\OLIH
IXQFWLRQVEXWGRQRWFRQVWLWXWHDVXEVWDQWLDOGLVUXSWLRQ
H ,VDFRQJHQLWDODQRPDO\ELUWKGHIHFW
I
2WKHUVLWXDWLRQV
0HGLFDORUVFLHQWLILFMXGJPHQWVKRXOGEHH[HUFLVHGLQGHFLGLQJZKHWKHUUHSRUWLQJLV
DSSURSULDWHLQRWKHUVLWXDWLRQVVXFKDVLPSRUWDQWPHGLFDOHYHQWVWKDWPD\QRWEH
LPPHGLDWHO\OLIHWKUHDWHQLQJRUUHVXOWLQGHDWKRUKRVSLWDOL]DWLRQEXWPD\MHRSDUGL]HWKH
VXEMHFWRUPD\UHTXLUHPHGLFDORUVXUJLFDOLQWHUYHQWLRQWRSUHYHQWRQHRIWKHRWKHU
RXWFRPHVOLVWHGLQWKHDERYHGHILQLWLRQ7KHVHVKRXOGDOVREHFRQVLGHUHGVHULRXV
([DPSOHVRIVXFKHYHQWVDUHLQYDVLYHRUPDOLJQDQWFDQFHUVLQWHQVLYHWUHDWPHQWLQDQ
HPHUJHQF\URRPRUDWKRPHIRUDOOHUJLFEURQFKRVSDVPEORRGG\VFUDVLDVRUFRQYXOVLRQV
WKDWGRQRWUHVXOWLQKRVSLWDOL]DWLRQRUGHYHORSPHQWRIGUXJGHSHQGHQF\RUGUXJDEXVH
J ,VDVVRFLDWHGZLWKOLYHULQMXU\DQG LPSDLUHGOLYHUIXQFWLRQGHILQHGDV
$/7∀[8/1DQGWRWDOELOLUXELQ ∀[8/1!GLUHFWRU
$/7∀[8/1DQG,15 !
6HUXPELOLUXELQIUDFWLRQDWLRQVKRXOGEHSHUIRUPHGLIWHVWLQJLVDYDLODEOHLIXQDYDLODEOH
PHDVXUHXULQDU\ELOLUXELQYLDGLSVWLFN,IIUDFWLRQDWLRQLVXQDYDLODEOHDQG$/7∀[8/1
DQGWRWDOELOLUXELQ∀[8/1WKHQWKHHYHQWLVVWLOOWREHUHSRUWHGDVDQ6$(
,15WHVWLQJQRWUHTXLUHGSHUSURWRFRODQGWKHWKUHVKROGYDOXHGRHVQRWDSSO\WR
VXEMHFWVUHFHLYLQJDQWLFRDJXODQWV,I,15PHDVXUHPHQWLVREWDLQHGWKHYDOXHLVWREH
UHFRUGHGRQWKH6$(IRUP
5HIHUWR$SSHQGL[ IRUWKHUHTXLUHGOLYHUFKHPLVWU\IROORZXSLQVWUXFWLRQV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
86

'HILQLWLRQRI&DUGLRYDVFXODU(YHQWV
&DUGLRYDVFXODU(YHQWV&9'HILQLWLRQ
,QYHVWLJDWRUVZLOOEHUHTXLUHGWRILOORXWWKHVSHFLILF&9HYHQWSDJHRIWKH&5)IRUWKH
IROORZLQJ$(VDQG6$(V
0\RFDUGLDOLQIDUFWLRQXQVWDEOHDQJLQD
&RQJHVWLYHKHDUWIDLOXUH
$UUK\WKPLDV
9DOYXORSDWK\
3XOPRQDU\K\SHUWHQVLRQ
&HUHEURYDVFXODUHYHQWVVWURNHDQGWUDQVLHQWLVFKHPLFDWWDFN
3HULSKHUDODUWHULDOWKURPERHPEROLVP
'HHSYHQRXVWKURPERVLVSXOPRQDU\HPEROLVP
5HYDVFXODUL]DWLRQ

5HFRUGLQJRI$(V$'5VDQG6$(V
$(VDQG6$(5HFRUGLQJ
:KHQDQ$($'5V6$(RFFXUVLWLVWKHUHVSRQVLELOLW\RIWKHLQYHVWLJDWRUWRUHYLHZDOO
GRFXPHQWDWLRQHJKRVSLWDOSURJUHVVQRWHVODERUDWRU\DQGGLDJQRVWLFVUHSRUWVUHODWLYH
WRWKHHYHQW
7KHLQYHVWLJDWRUZLOOWKHQUHFRUGDOOUHOHYDQWLQIRUPDWLRQUHJDUGLQJDQ$($'5V6$(
LQWKH&5)
,WLVQRW DFFHSWDEOHIRUWKHLQYHVWLJDWRUWRVHQGSKRWRFRSLHVRIWKHVXEMHFW¶VPHGLFDO
UHFRUGVWR*6.LQOLHXRIFRPSOHWLRQRIWKH*6.$($'5V6$(&5)SDJH
7KHUHPD\EHLQVWDQFHVZKHQFRSLHVRIPHGLFDOUHFRUGVIRUFHUWDLQFDVHVDUHUHTXHVWHGE\
*6.,QWKLVLQVWDQFHDOOVXEMHFWLGHQWLILHUVZLWKWKHH[FHSWLRQRIWKHVXEMHFWQXPEHU
ZLOOEHEOLQGHGRQWKHFRSLHVRIWKHPHGLFDOUHFRUGVSULRUWRVXEPLVVLRQRIWR*6.
7KHLQYHVWLJDWRUZLOODWWHPSWWRHVWDEOLVKDGLDJQRVLVRIWKHHYHQWEDVHGRQVLJQV
V\PSWRPVDQGRURWKHUFOLQLFDOLQIRUPDWLRQ,QVXFKFDVHVWKHGLDJQRVLVZLOOEH
GRFXPHQWHGDVWKH$($'5V6$(DQGQRWWKHLQGLYLGXDOVLJQVV\PSWRPV
6XEMHFWFRPSOHWHG9DOXH(YLGHQFHDQG2XWFRPHVTXHVWLRQQDLUHVDQGWKHFROOHFWLRQRI
$($'5VGDWDDUHLQGHSHQGHQWFRPSRQHQWVRIWKHVWXG\
5HVSRQVHVWRHDFKTXHVWLRQLQWKH9DOXH(YLGHQFHDQG2XWFRPHVTXHVWLRQQDLUHZLOOEH
WUHDWHGLQDFFRUGDQFHZLWKVWDQGDUGVFRULQJDQGVWDWLVWLFDOSURFHGXUHVGHWDLOHGE\WKH
VFDOH¶VGHYHORSHU
7KHXVHRIDVLQJOHTXHVWLRQIURPDPXOWLGLPHQVLRQDOKHDOWKVXUYH\WRGHVLJQDWHDFDXVH
HIIHFWUHODWLRQVKLSWRDQ$($'5VLVLQDSSURSULDWH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
87

(YDOXDWLQJ$(V$'5VDQG6$(V
$VVHVVPHQWRI,QWHQVLW\
7KHLQYHVWLJDWRUZLOOPDNH DQDVVHVVPHQWRILQWHQVLW\IRUHDFK$($'5VDQG6$(
UHSRUWHGGXULQJWKHVWXG\DQGZLOODVVLJQLWWRRQHRIWKHIROORZLQJFDWHJRULHV
0LOG$QHYHQWWKDWLVHDVLO\WROHUDWHGE\WKHVXEMHFWFDXVLQJPLQLPDOGLVFRPIRUWDQG
QRWLQWHUIHULQJZLWKHYHU\GD\DFWLYLWLHV
0RGHUDWH$QHYHQWWKDWLVVXIILFLHQWO\GLVFRPIRUWLQJWRLQWHUIHUHZLWKQRUPDOHYHU\GD\
DFWLYLWLHV
6HYHUH$QHYHQWWKDWSUHYHQWVQRUPDOHYHU\GD\DFWLYLWLHV DQ$($'5VWKDWLV
DVVHVVHGDVVHYHUHZLOOQRWEHFRQIXVHGZLWKDQ6$(6HYHULW\LVDFDWHJRU\XWLOL]HGIRU
UDWLQJWKHLQWHQVLW\RIDQHYHQWDQGERWK$(V$'5VDQG6$(VFDQEHDVVHVVHGDV
VHYHUH
$QHYHQWLVGHILQHGDVµVHULRXV¶ZKHQLWPHHWVDWOHDVWRQHRIWKHSUHGHILQHGRXWFRPHVDV
GHVFULEHGLQWKHGHILQLWLRQRIDQ6$(
$VVHVVPHQWRI&DXVDOLW\
7KHLQYHVWLJDWRULVREOLJDWHGWRDVVHVVWKHUHODWLRQVKLSEHWZHHQVWXG\WUHDWPHQWDQGWKH
RFFXUUHQFHRIHDFK$(6$(
$UHDVRQDEOHSRVVLELOLW\LVPHDQWWRFRQYH\WKDWWKHUHDUHIDFWVHYLGHQFHRUDUJXPHQWV
WRVXJJHVWDFDXVDOUHODWLRQVKLSUDWKHUWKDQDUHODWLRQVKLSFDQQRWEHUXOHGRXW
7KHLQYHVWLJDWRUZLOOXVHFOLQLFDOMXGJPHQWWRGHWHUPLQHWKHUHODWLRQVKLS
$OWHUQDWLYHFDXVHVVXFKDVQDWXUDOKLVWRU\RIWKHXQGHUO\LQJGLVHDVHVFRQFRPLWDQW
WKHUDS\RWKHUULVNIDFWRUVDQGWKHWHPSRUDOUHODWLRQVKLSRIWKHHYHQWWRWKHVWXG\
WUHDWPHQWZLOOEHFRQVLGHUHGDQGLQYHVWLJDWHG
7KHLQYHVWLJDWRUZLOODOVRFRQVXOWWKH,QYHVWLJDWRU%URFKXUH,%DQGRU3URGXFW
,QIRUPDWLRQIRUPDUNHWHGSURGXFWVLQWKHGHWHUPLQDWLRQRIKLVKHUDVVHVVPHQW
)RUHDFK$(6$(WKHLQYHVWLJDWRUPXVW GRFXPHQWLQWKHPHGLFDOQRWHVWKDWKHVKHKDV
UHYLHZHGWKH$(6$(DQGKDVSURYLGHGDQDVVHVVPHQWRIFDXVDOLW\
7KHUHPD\EHVLWXDWLRQVZKHQDQ6$(KDVRFFXUUHGDQGWKHLQYHVWLJDWRUKDVPLQLPDO
LQIRUPDWLRQWRLQFOXGHLQWKHLQLWLDO UHSRUWWR*6.+RZHYHULWLVYHU\LPSRUWDQWWKDW
WKHLQYHVWLJDWRUDOZD\VPDNHDQDVVHVVPHQWRIFDXVDOLW\IRUHYHU\HYHQWSULRUWRWKH
LQLWLDOWUDQVPLVVLRQRIWKH6$(GDWDWR*6.
7KHLQYHVWLJDWRUPD\FKDQJHKLVKHURSLQLRQRIFDXVDOLW\LQOLJKWRIIROORZXS
LQIRUPDWLRQDPHQGLQJWKH6$(GDWDFROOHFWLRQWRRODFFRUGLQJO\
7KHFDXVDOLW\DVVHVVPHQWLVRQHRIWKHFULWHULDXVHGZKHQGHWHUPLQLQJUHJXODWRU\
UHSRUWLQJUHTXLUHPHQWV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
88
)ROORZXSRI$(VDQG6$(V
7KHLQYHVWLJDWRULVREOLJDWHGWRSHUIRUPRUDUUDQJHIRUWKHFRQGXFWRIVXSSOHPHQWDO
PHDVXUHPHQWVDQGRUHYDOXDWLRQVDVPD\EHLQGLFDWHGRUDVUHTXHVWHGE\*6.WR
HOXFLGDWHDVIXOO\DVSRVVLEOHWKHQDWXUHDQGRUFDXVDOLW\RIWKH$(RU6$(
7KHLQYHVWLJDWRULVREOLJDWHGWRDVVLVW7KLVPD\LQFOXGHDGGLWLRQDOODERUDWRU\WHVWVRU
LQYHVWLJDWLRQVKLVWRSDWKRORJLFDOH[DPLQDWLRQVRUFRQVXOWDWLRQZLWKRWKHUKHDOWKFDUH
SURIHVVLRQDOV
,IDVXEMHFWGLHVGXULQJSDUWLFLSDWLRQLQWKHVWXG\RUGXULQJDUHFRJQL]HGIROORZXSSHULRG
WKHLQYHVWLJDWRUZLOOSURYLGH*6.ZLWKDFRS\RIDQ\SRVWPRUWHPILQGLQJVLQFOXGLQJ
KLVWRSDWKRORJ\
1HZRUXSGDWHGLQIRUPDWLRQZLOOEHUHFRUGHGLQWKHRULJLQDOO\FRPSOHWHG&5)
7KHLQYHVWLJDWRUZLOOVXEPLWDQ\XSGDWHG6$(GDWDWR*6.ZLWKLQWKHGHVLJQDWHG
UHSRUWLQJWLPHIUDPHV

5HSRUWLQJRI6$(V WR*6.
6$(UHSRUWLQJWR*6.YLDHOHFWURQLFGDWDFROOHFWLRQWRRO
3ULPDU\PHFKDQLVPIRUUHSRUWLQJ6$(VWR*6.ZLOOEHWKHHOHFWURQLFGDWDFROOHFWLRQWRRO
,IWKHHOHFWURQLFV\VWHPLVXQDYDLODEOHIRUJUHDWHUWKDQKRXUVWKHVLWHZLOOXVHWKHSDSHU
6$(GDWDFROOHFWLRQWRRODQGID[LWWRWKH6$(FRRUGLQDWRU
6LWHZLOOHQWHUWKHVHULRXVDGYHUVHHYHQWGDWDLQWRWKHHOHFWURQLFV\VWHPDVVRRQDVLW
EHFRPHVDYDLODEOH
7KHLQYHVWLJDWRUZLOOEHUHTXLUHGWRFRQILUPUHYLHZRIWKH6$(FDXVDOLW\E\WLFNLQJWKH
µUHYLHZHG¶ER[DWWKHERWWRPRIWKHH&5)SDJHZLWKLQKRXUVRIVXEPLVVLRQRIWKH
6$(
$IWHUWKHVWXG\LVFRPSOHWHGDWDJLYHQVLWHWKHHOHFWURQLFGDWDFROOHFWLRQWRROHJ
,Q)RUPV\VWHPZLOOEHWDNHQRIIOLQHWRSUHYHQWWKHHQWU\RIQHZGDWDRUFKDQJHVWR
H[LVWLQJGDWD
,IDVLWHUHFHLYHVDUHSRUWRIDQHZ6$(IURPDVWXG\VXEMHFWRUUHFHLYHVXSGDWHGGDWDRQD
SUHYLRXVO\UHSRUWHG6$(DIWHUWKHHOHFWURQLFGDWDFROOHFWLRQWRROKDVEHHQWDNHQRIIOLQH
WKHVLWHFDQUHSRUWWKLVLQIRUPDWLRQRQDSDSHU6$(IRUPRUWR WKH6$(FRRUGLQDWRUE\
WHOHSKRQH
&RQWDFWVIRU6$(UHFHLSWFDQEHIRXQGDWWKHEHJLQQLQJRIWKLVSURWRFRORQWKH
6SRQVRU0HGLFDO0RQLWRU&RQWDFW,QIRUPDWLRQSDJH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
89

$SSHQGL[*HQHWLF5HVHDUFK
*HQHWLF5HVHDUFK2EMHFWLYHVDQG$QDO\VHV
7KHREMHFWLYHVRIWKHJHQHWLFUHVHDUFKDUHWRLQYHVWLJDWHWKHUHODWLRQVKLSEHWZHHQJHQHWLF
YDULDQWVDQG
!
5HVSRQVHWRPHGLFLQHLQFOXGLQJDQ\WUHDWPHQWUHJLPHQVXQGHULQYHVWLJDWLRQLQWKLV
VWXG\RUDQ\FRQFRPLWDQWPHGLFLQHV
!
$VWKPDVXVFHSWLELOLW\VHYHULW\DQGSURJUHVVLRQDQGUHODWHGFRQGLWLRQV
*HQHWLFGDWDPD\EHJHQHUDWHGZKLOHWKHVWXG\LVXQGHUZD\RUIROORZLQJFRPSOHWLRQRI
WKHVWXG\*HQHWLFHYDOXDWLRQVPD\LQFOXGHIRFXVHGFDQGLGDWHJHQHDSSURDFKHVDQGRU
H[DPLQDWLRQRIDODUJHQXPEHURIJHQHWLFYDULDQWVWKURXJKRXWWKHJHQRPHZKROHJHQRPH
DQDO\VHV*HQHWLFDQDO\VHVZLOOXWLOL]HGDWDFROOHFWHGLQWKHVWXG\DQGZLOOEHOLPLWHGWR
XQGHUVWDQGLQJWKHREMHFWLYHVKLJKOLJKWHGDERYH$QDO\VHVPD\EHSHUIRUPHGXVLQJGDWD
IURPPXOWLSOHFOLQLFDOVWXGLHVWRLQYHVWLJDWHWKHVHUHVHDUFKREMHFWLYHV
$SSURSULDWHGHVFULSWLYHDQGRUVWDWLVWLFDODQDO\VLVPHWKRGVZLOOEHXVHG$GHWDLOHG
GHVFULSWLRQRIDQ\SODQQHGDQDO\VHVZLOOEHGRFXPHQWHGLQD5HSRUWLQJDQG$QDO\VLV3ODQ
5$3SULRUWRLQLWLDWLRQRIWKHDQDO\VLV3ODQQHGDQDO\VHVDQGUHVXOWVRIJHQHWLF
LQYHVWLJDWLRQVZLOOEHUHSRUWHGHLWKHUDVSDUWRIWKHFOLQLFDO5$3DQGVWXG\UHSRUWRULQD
VHSDUDWHJHQHWLFV5$3DQGUHSRUWDVDSSURSULDWH
6WXG\3RSXODWLRQ
$Q\VXEMHFWZKRLVHQUROOHGLQWKHVWXG\FDQSDUWLFLSDWHLQJHQHWLFUHVHDUFK$Q\ VXEMHFW
ZKRKDVUHFHLYHGDQ DOORJHQHLF ERQHPDUURZWUDQVSODQWPXVWEHH[FOXGHGIURPWKH
JHQHWLFUHVHDUFK
6WXG\$VVHVVPHQWVDQG3URFHGXUHV
$NH\FRPSRQHQWRIVXFFHVVIXOJHQHWLFUHVHDUFKLVWKHFROOHFWLRQRIVDPSOHVGXULQJ
FOLQLFDOVWXGLHV&ROOHFWLRQRIVDPSOHVHYHQZKHQQRDSULRUL K\SRWKHVLVKDVEHHQ
LGHQWLILHGPD\HQDEOHIXWXUHJHQHWLFDQDO\VHVWREHFRQGXFWHGWRKHOSXQGHUVWDQG
YDULDELOLW\LQGLVHDVHDQGPHGLFLQHUHVSRQVH
!
$POVDOLYDVDPSOHZLOOEHWDNHQIRU'HR[\ULERQXFOHLFDFLG'1$H[WUDFWLRQ$
VDOLYDVDPSOHLVFROOHFWHGDWWKHEDVHOLQHYLVLW9LVLWDIWHUWKHVXEMHFWKDVEHHQ
UDQGRPL]HGDQGSURYLGHGLQIRUPHGFRQVHQWIRUJHQHWLFUHVHDUFK,QVWUXFWLRQVIRU
FROOHFWLRQDQGVKLSSLQJRIWKHJHQHWLFVDPSOHDUHGHVFULEHGLQWKHODERUDWRU\
PDQXDO7KH'1$IURPWKHVDOLYDVDPSOHPD\XQGHUJRTXDOLW\FRQWURODQDO\VHVWR
FRQILUPWKHLQWHJULW\RIWKHVDPSOH,IWKHUHDUHFRQFHUQVUHJDUGLQJWKHTXDOLW\RI
WKHVDPSOHWKHQWKHVDPSOHPD\EHGHVWUR\HG7KHVDOLYDVDPSOHLVWDNHQRQD
VLQJOHRFFDVLRQXQOHVVDGXSOLFDWHVDPSOHLVUHTXLUHGGXHWRDQLQDELOLW\WRXWLOL]H
WKHRULJLQDOVDPSOH
7KHJHQHWLFVDPSOHLVODEHOOHGRU³FRGHG´ZLWKWKHVDPHVWXG\VSHFLILFQXPEHUXVHGWR
ODEHORWKHUVDPSOHVDQGGDWDLQWKHVWXG\7KLVQXPEHUFDQEHWUDFHGRUOLQNHGEDFNWRWKH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
90
VXEMHFWE\WKHLQYHVWLJDWRURUVLWHVWDII&RGHGVDPSOHVGRQRWFDUU\SHUVRQDOLGHQWLILHUV
VXFKDVQDPHRUVRFLDOVHFXULW\QXPEHU
6DPSOHVZLOOEHVWRUHGVHFXUHO\DQGPD\EHNHSWIRUXSWR\HDUVDIWHUWKHODVWVXEMHFW
FRPSOHWHVWKHVWXG\RU*6.PD\GHVWUR\WKHVDPSOHVVRRQHU*6.RUWKRVHZRUNLQJ
ZLWK*6.IRUH[DPSOHRWKHUUHVHDUFKHUVZLOORQO\XVHVDPSOHVFROOHFWHGIURPWKHVWXG\
IRUWKHSXUSRVHVWDWHGLQWKLVSURWRFRODQGLQWKHLQIRUPHGFRQVHQWIRUP6DPSOHVPD\EH
XVHGDVSDUWRIWKH GHYHORSPHQWRIDFRPSDQLRQGLDJQRVWLFWRVXSSRUWWKH*6.PHGLFLQDO
SURGXFW
6XEMHFWVFDQUHTXHVWWKHLUVDPSOHWREHGHVWUR\HGDWDQ\WLPH
,QIRUPHG&RQVHQW
6XEMHFWVZKRGRQRWZLVKWRSDUWLFLSDWHLQWKHJHQHWLFUHVHDUFKPD\VWLOOSDUWLFLSDWHLQWKH
VWXG\ *HQHWLFLQIRUPHGFRQVHQWPXVWEHREWDLQHGSULRUWRDQ\VDOLYDEHLQJWDNHQ
6XEMHFW:LWKGUDZDOIURP6WXG\
,IDVXEMHFWZKRKDVFRQVHQWHGWRSDUWLFLSDWHLQJHQHWLFUHVHDUFKZLWKGUDZVIURPWKH
FOLQLFDOVWXG\IRUDQ\UHDVRQRWKHUWKDQEHLQJORVWWRIROORZXS WKHVXEMHFWZLOOEHJLYHQD
FKRLFHRIRQHRIWKHIROORZLQJRSWLRQVFRQFHUQLQJWKHJHQHWLFVDPSOHLIDOUHDG\
FROOHFWHG
! &RQWLQXHWRSDUWLFLSDWHLQWKHJHQHWLFUHVHDUFKLQZKLFKFDVHWKHJHQHWLF'1$
VDPSOHLVUHWDLQHG
! 'LVFRQWLQXHSDUWLFLSDWLRQLQWKHJHQHWLFUHVHDUFKDQGGHVWUR\WKHJHQHWLF'1$
VDPSOH
,IDVXEMHFWZLWKGUDZVFRQVHQWIRUJHQHWLFUHVHDUFKRUUHTXHVWVVDPSOHGHVWUXFWLRQIRUDQ\
UHDVRQWKHLQYHVWLJDWRUPXVWFRPSOHWHWKHDSSURSULDWHGRFXPHQWDWLRQWRUHTXHVWVDPSOH
GHVWUXFWLRQZLWKLQWKHWLPHIUDPHVSHFLILHGE\*6.DQGPDLQWDLQWKHGRFXPHQWDWLRQLQ
WKHVLWHVWXG\UHFRUGV
*HQRW\SHGDWDPD\EHJHQHUDWHGGXULQJWKHVWXG\RUDIWHUFRPSOHWLRQRIWKHVWXG\DQG
PD\EHDQDO\]HGGXULQJWKHVWXG\RUVWRUHGIRUIXWXUHDQDO\VLV
! ,IDVXEMHFWZLWKGUDZVFRQVHQWIRUJHQHWLFUHVHDUFKDQGJHQRW\SHGDWDKDVQRW
EHHQDQDO\]HGLWZLOOQRWEHDQDO\]HGRUXVHGIRUIXWXUHUHVHDUFK
! *HQHWLFGDWDWKDWKDVEHHQDQDO\]HGDWWKHWLPHRIZLWKGUDZQFRQVHQWZLOO
FRQWLQXHWREHVWRUHGDQGXVHGDVDSSURSULDWH
6FUHHQDQG%DVHOLQH)DLOXUHV
,IDVDPSOHIRUJHQHWLFUHVHDUFKKDVEHHQFROOHFWHGDQGLWLVGHWHUPLQHGWKDWWKHVXEMHFW
GRHVQRWPHHWWKHHQWU\FULWHULDIRUSDUWLFLSDWLRQLQWKHVWXG\WKHQWKHLQYHVWLJDWRUVKRXOG
LQVWUXFWWKHVXEMHFWWKDWWKHLUJHQHWLFVDPSOHZLOOEHGHVWUR\HG1RIRUPVDUHUHTXLUHGWR
FRPSOHWHWKLVSURFHVVDVLWZLOOEHFRPSOHWHGDVSDUWRIWKHFRQVHQWDQGVDPSOH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
91
UHFRQFLOLDWLRQSURFHVV,QWKLVLQVWDQFHDVDPSOHGHVWUXFWLRQIRUPZLOOQRWEHDYDLODEOHWR
LQFOXGHLQWKHVLWHILOHV
3URYLVLRQRI6WXG\5HVXOWVDQG&RQILGHQWLDOLW\RI6XEMHFW¶V*HQHWLF'DWD
*6.PD\VXPPDUL]HWKHJHQHWLFUHVHDUFKUHVXOWVLQWKHFOLQLFDOVWXG\UHSRUWRU
VHSDUDWHO\DQGPD\SXEOLVKWKHUHVXOWVLQVFLHQWLILFMRXUQDOV
*6.PD\VKDUHJHQHWLFUHVHDUFKGDWDZLWKRWKHUVFLHQWLVWVWR IXUWKHUVFLHQWLILF
XQGHUVWDQGLQJLQDOLJQPHQWZLWKWKHLQIRUPHGFRQVHQW*6.GRHVQRWLQIRUPWKHVXEMHFW
IDPLO\PHPEHUVLQVXUHUVRUHPSOR\HUVRILQGLYLGXDOJHQRW\SLQJUHVXOWVWKDWDUHQRW
NQRZQWREHUHOHYDQWWRWKHVXEMHFW¶VPHGLFDOFDUHDWWKHWLPHRIWKHVWXG\XQOHVV
UHTXLUHGE\ODZ7KLVLVGXHWRWKHIDFWWKDWWKHLQIRUPDWLRQJHQHUDWHGIURPJHQHWLF
VWXGLHVLVJHQHUDOO\SUHOLPLQDU\LQQDWXUHDQGWKHUHIRUHWKHVLJQLILFDQFHDQGVFLHQWLILF
YDOLGLW\RIWKHUHVXOWVDUHXQGHWHUPLQHG)XUWKHUGDWDJHQHUDWHGLQDUHVHDUFKODERUDWRU\
PD\QRWPHHWUHJXODWRU\UHTXLUHPHQWVIRULQFOXVLRQLQFOLQLFDOFDUH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
92

$SSHQGL[&ROOHFWLRQRI3UHJQDQF\,QIRUPDWLRQ
!
,QYHVWLJDWRUZLOOFROOHFWSUHJQDQF\LQIRUPDWLRQRQDQ\IHPDOHVXEMHFWZKR
EHFRPHVSUHJQDQWZKLOHSDUWLFLSDWLQJLQWKLVVWXG\
!
,QIRUPDWLRQZLOOEHUHFRUGHGRQWKHDSSURSULDWHIRUPDQGVXEPLWWHGWR*6.
ZLWKLQZHHNVRIOHDUQLQJRIDVXEMHFW
VSUHJQDQF\
!
6XEMHFWZLOOEHIROORZHGWRGHWHUPLQHWKHRXWFRPHRIWKHSUHJQDQF\7KH
LQYHVWLJDWRUZLOOFROOHFWIROORZXSLQIRUPDWLRQRQPRWKHUDQGLQIDQWZKLFKZLOO
EHIRUZDUGHGWR*6.*HQHUDOO\IROORZXSZLOOQRWEHUHTXLUHGIRUORQJHUWKDQ
WRZHHNVEH\RQGWKHHVWLPDWHGGHOLYHU\GDWH
!
$Q\WHUPLQDWLRQRISUHJQDQF\ZLOOEHUHSRUWHGUHJDUGOHVVRIIRHWDOVWDWXV
SUHVHQFHRUDEVHQFHRIDQRPDOLHVRULQGLFDWLRQIRUSURFHGXUH
!
:KLOHSUHJQDQF\LWVHOILVQRWFRQVLGHUHGWREHDQ$(RU6$(DQ\SUHJQDQF\
FRPSOLFDWLRQRUHOHFWLYHWHUPLQDWLRQRIDSUHJQDQF\ZLOOEHUHSRUWHGDVDQ$(RU
6$(
!
$VSRQWDQHRXVDERUWLRQLVDOZD\VFRQVLGHUHGWREHDQ6$(DQGZLOOEHUHSRUWHGDV
VXFK
!
$Q\6$(RFFXUULQJDVDUHVXOWRIDSRVWVWXG\SUHJQDQF\ZKLFKLVFRQVLGHUHG
UHDVRQDEO\UHODWHGWRWKHVWXG\WUHDWPHQWE\WKHLQYHVWLJDWRUZLOOEHUHSRUWHGWR
*6.DVGHVFULEHGLQ$SSHQGL[:KLOHWKHLQYHVWLJDWRULVQRWREOLJDWHGWR
DFWLYHO\VHHNWKLVLQIRUPDWLRQLQIRUPHUVWXG\SDUWLFLSDQWVKHRUVKHPD\OHDUQRI
DQ6$(WKURXJKVSRQWDQHRXVUHSRUWLQJ
$Q\IHPDOHVXEMHFWZKREHFRPHVSUHJQDQWZKLOHSDUWLFLSDWLQJ
!
ZLOOEHZLWKGUDZQIURPWKHVWXG\
!
,QYHVWLJDWRUZLOODWWHPSWWRFROOHFWSUHJQDQF\LQIRUPDWLRQRQDQ\IHPDOHSDUWQHU
RIDPDOHVWXG\VXEMHFWZKREHFRPHVSUHJQDQWZKLOHSDUWLFLSDWLQJLQWKLVVWXG\
7KLVDSSOLHVRQO\WRVXEMHFWVZKRDUHUDQGRPL]HGWRUHFHLYHVWXG\PHGLFDWLRQ
!
$IWHUREWDLQLQJWKHQHFHVVDU\VLJQHGLQIRUPHGFRQVHQWIURPWKHIHPDOHSDUWQHU
GLUHFWO\WKHLQYHVWLJDWRUZLOOUHFRUGSUHJQDQF\LQIRUPDWLRQRQWKHDSSURSULDWH
IRUPDQGVXEPLWLWWR*6.ZLWKLQZHHNVRIOHDUQLQJRIWKHSDUWQHU¶VSUHJQDQF\
!
3DUWQHUZLOODOVREHIROORZHGWRGHWHUPLQHWKHRXWFRPHRIWKHSUHJQDQF\
,QIRUPDWLRQRQWKHVWDWXVRIWKHPRWKHUDQGFKLOGZLOOEHIRUZDUGHGWR*6.
*HQHUDOO\IROORZXSZLOOEHQRORQJHUWKDQWRZHHNVIROORZLQJWKHHVWLPDWHGGHOLYHU\
GDWH$Q\WHUPLQDWLRQRIWKHSUHJQDQF\ZLOOEHUHSRUWHGUHJDUGOHVVRIIHWDOVWDWXV
SUHVHQFHRUDEVHQFHRIDQRPDOLHVRULQGLFDWLRQIRUSURFHGXUH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
93

$SSHQGL[3URWRFRO&KDQJHV
3URWRFRO&KDQJHVIRU$PHQGPHQW$8*IURP2ULJLQDO3URWRFRO
)(%
7KLVSURWRFRODPHQGPHQWKDVEHHQFUHDWHGWRFRUUHFWPLVWDNHVLQWKHZRUGLQJ RIWKH
LQKDOHUHUURUVTXHVWLRQQDLUHVIRUWKH (//,37$',6.86 DQG7XUEXKDOHULQKDOHUV
ZKLFKDUHLQFOXGHGLQ6HFWLRQRIWKHSURWRFRO$OOUHIHUHQFHVWRµ7\SH$HUURUV¶DQG
µRYHUDOOHUURUV¶ZLWKLQWKHSURWRFROKDYHEHHQFKDQJHGWRµFULWLFDO¶DQGµQRQFULWLFDO¶
HUURUVUHVSHFWLYHO\IRUFRQVLVWHQF\ZLWKWKHLQKDOHUHUURUVTXHVWLRQQDLUHZRUNVKHHWV
6WRUDJHFRQGLWLRQLQVWUXFWLRQVIRU6HUHWLGHIOXWLFDVRQHSURSLRQDWHVDOPHWHUROLQ6HFWLRQ
KDYHEHHQDPHQGHG6HFWLRQRIWKHSURWRFROVWDWHVWKDWWKHVWRUDJHFRQGLWLRQVRI
6HUHWLGHIOXWLFDVRQHSURSLRQDWHVDOPHWHUROPXVWEHVWRUHGDWWHPSHUDWXUHVXSWR#&
$WWKHSRLQWDWZKLFKWKHSURWRFROZDVDSSURYHGLWZDVLQWHQGHGWKDW6HUHWLGHFRPPHUFLDO
VWRFNZRXOGEHSURYLGHGIRUXVHLQWKLVVWXG\+RZHYHUGXHWRODEHOOLQJUHTXLUHPHQWV
WKLVZDVQRWSRVVLEOHDQGWKHFOLQLFDOWULDOLPDJHQHHGHGWREHXVHGLQVWHDG$OO6HUHWLGH
IOXWLFDVRQHSURSLRQDWHVDOPHWHURO'3,VVKRXOGEHVWRUHGDWWHPSHUDWXUHVEHWZHHQ
#&
7KHZRUGLQJIRUWKHUHFRPPHQGHGQXPEHURIVSLURPHWU\HIIRUWVKDVEHHQUHYLVHG
1HZWH[WKDVEHHQLQFOXGHGZLWKUHJDUGVWRLQYHVWLJDWLRQDOSURGXFWPDOIXQFWLRQLQ
6HFWLRQ
7KHVHFRQGDU\PHGLFDOPRQLWRUFRQWDFWLQIRUPDWLRQKDVEHHQUHYLVHGWRLQFOXGHDQHZ
VWXG\SK\VLFLDQ
2WKHUPLQRUFRUUHFWLRQVDQGHGLWVKDYHEHHQPDGH
0HWKRGRI$PHQGPHQW
2ULJLQDODQGDPHQGHGWH[WVDUHVSHFLILHGDVIROORZV
2ULJLQDOWH[WDVZULWWHQLQWKHRULJLQDOSURWRFRO
5HYLVHGWH[WDVZULWWHQLQ$PHQGPHQW1RZLWKUHYLVLRQVLQEROGIRQW
3URWRFROV\QRSVLVIRUVWXG\+=$DQG6HFWLRQ6HFRQGDU\
2EMHFWLYHVDQG(QGSRLQWV
2ULJLQDOWDEOH
Secondary
!
7RDVVHVVHIIHFWRI))9,RQDVWKPD
FRQWUROFRPSDUHGZLWKXVXDO,&6/$%$
IL[HGFRPELQDWLRQDW:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQ$&7VFRUHDW
:HHN9LVLW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
94
Secondary
!
7RDVVHVV(//,37$LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXV DQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVPDNLQJDWOHDVW
7\SH$HUURUOLNHO\WREHFULWLFDODQG
RYHUDOOHUURUVDW:HHN9LVLWDQG
DW:HHN9LVLWLQGHSHQGHQWO\RI
WKHXVHDW:HHN9LVLW
Other
!
7RDVVHVVHIIHFWRI))9,RQWURXJKSUH
GRVH)(9FRPSDUHGZLWKXVXDO
,&6/$%$IL[HGFRPELQDWLRQDW:HHN
9LVLW
7RDVVHVVWKHHIIHFWRI))9,RQUHVSRQVHWR
WUHDWPHQWDW:HHN9LVLWDQG:HHN
9LVLW
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQDW:HHN9LVLWDQG:HHN
9LVLW
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQRYHUWKHVWXG\SHULRG
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIHDW:HHN9LVLW
&KDQJHIURPEDVHOLQHLQWURXJKSUHGRVH
)(9DW:HHN9LVLW
$&7VFRUHRUSRLQWLQFUHDVHIURP
EDVHOLQHLQ$&7DW:HHN9LVLWDQG
:HHN9LVLW1RWH$SRLQWLQFUHDVH
LQ$&7WRWDOVFRUHZDVVXJJHVWHGDVWKH
0LQLPDO&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]@
!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN
9LVLWDQG:HHN9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
1XPEHURIVXEMHFWZLWKDWOHDVWVHYHUH
DVWKPDH[DFHUEDWLRQQXPEHURIVHYHUH
DVWKPDH[DFHUEDWLRQDQGDQQXDOVHYHUH
H[DFHUEDWLRQUDWHRYHUWKHVWXG\SHULRG
&KDQJH IURP EDVHOLQH LQ WRWDO VFRUH DQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUHDW:HHN
9LVLW
$Q LQFUHDVH IURP EDVHOLQH RI   LQ
$4/4VWRWDOVFRUHDW:HHN9LVLW
$Q LQFUHDVH IURP EDVHOLQH RI   LQ
$4/4V HQYLURQPHQWDO VWLPXOL GRPDLQ

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
95
Secondary
7RDVVHVV3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH
DVVHVVPHQWZLWKGLIIHUHQWLQKDOHUV DW
:HHN9LVLW
7RHYDOXDWHWKH6DIHW\RI))9,FRPSDUHG
ZLWKXVXDO,&6/$%$)36DQG%XG)
VFRUHDW:HHN9LVLW
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVHIURPEDVHOLQHRILQ$4/46
,QGLYLGXDOGRPDLQVFRUHVDW:HHN9LVLW

&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
+HDOWK
VWDWXV
XVLQJ
WKH
(XUR4RO
4XHVWLRQQDLUH (4' DW :HHN 
9LVLW
6FRUH RI 3$6$3 4XHVWLRQQDLUH 3DWLHQW
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN
9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
)UHTXHQF\ DQG W\SH RI VHULRXV
DGYHUVHHYHQWV
)UHTXHQF\DQGW\SHRIQRQVHULRXV
DGYHUVH GUXJ UHDFWLRQV UHODWHG WR
WUHDWPHQW
5HYLVHGWDEOH
Secondary
!
7RDVVHVVHIIHFWRI))9,RQDVWKPD
FRQWUROFRPSDUHGZLWKXVXDO,&6/$%$
IL[HGFRPELQDWLRQDW:HHN9LVLW
!
7RDVVHVV(//,37$LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXV DQG
7XUEXKDOHUDW:HHN9LVLW DQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQ$&7VFRUHDW
:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVPDNLQJDWOHDVW
FULWLFDOHUURUDQGQRQFULWLFDOHUURU
DW:HHN9LVLWDQGDW:HHN
9LVLW LQGHSHQGHQWO\RIWKHXVHDW
:HHN9LVLW
Other
!
7RDVVHVVHIIHFWRI))9,RQWURXJKSUH
&KDQJHIURPEDVHOLQHLQWURXJKSUHGRVH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
96
Secondary
GRVH)(9FRPSDUHGZLWKXVXDO
,&6/$%$IL[HGFRPELQDWLRQDW:HHN
9LVLW
7RDVVHVVWKHHIIHFWRI))9,RQUHVSRQVHWR
WUHDWPHQWDW:HHN9LVLWDQG:HHN
9LVLW
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQDW:HHN9LVLWDQG:HHN
9LVLW
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQRYHUWKHVWXG\SHULRG
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIHDW:HHN9LVLW
)(9DW:HHN9LVLW
$&7VFRUHRUSRLQWLQFUHDVHIURP
EDVHOLQHLQ$&7DW:HHN9LVLWDQG
:HHN9LVLW1RWH$SRLQWLQFUHDVH
LQ$&7WRWDOVFRUHZDVVXJJHVWHGDVWKH
0LQLPDO&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]@
$&7VFRUHDW:HHN9LVLWDQG
:HHN9LVLW
&KDQJHIURPEDVHOLQHLQLQGLYLGXDO
TXHVWLRQVFRUHVIRU$&7DW:HHNV

!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN
9LVLWDQG:HHN9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
1XPEHURIVXEMHFWZLWKDWOHDVWVHYHUH
DVWKPDH[DFHUEDWLRQQXPEHURIVHYHUH
DVWKPDH[DFHUEDWLRQDQGDQQXDOVHYHUH
H[DFHUEDWLRQUDWHRYHUWKHVWXG\SHULRG
&KDQJH IURP EDVHOLQH LQ WRWDO VFRUH DQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUHDW:HHN
9LVLW
$Q LQFUHDVH IURP EDVHOLQH RI   LQ
$4/4VWRWDOVFRUHDW:HHN9LVLW
$Q LQFUHDVH IURP EDVHOLQH RI   LQ
$4/4V HQYLURQPHQWDO VWLPXOL GRPDLQ
VFRUHDW:HHN9LVLW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
97
Secondary
7RDVVHVV3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH
DVVHVVPHQWZLWKGLIIHUHQWLQKDOHUV DW
:HHN9LVLW
7RHYDOXDWHWKH6DIHW\RI))9,FRPSDUHG
ZLWKXVXDO,&6/$%$)36DQG%XG)
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVHIURPEDVHOLQHRILQ$4/46
,QGLYLGXDOGRPDLQVFRUHVDW:HHN9LVLW

&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
+HDOWK
VWDWXV
XVLQJ
WKH
(XUR4RO
4XHVWLRQQDLUH (4' DW :HHN 
9LVLW
6FRUH RI 3$6$3 4XHVWLRQQDLUH 3DWLHQW
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN
9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
)UHTXHQF\ DQG W\SH RI VHULRXV
DGYHUVHHYHQWV
)UHTXHQF\DQGW\SHRIQRQVHULRXV
DGYHUVH GUXJ UHDFWLRQV UHODWHG WR
WUHDWPHQW
3URWRFROV\QRSVLVIRUVWXG\+=$2YHUDOO'HVLJQ
2ULJLQDOWH[W
,QDGGLWLRQHDFKVXEMHFWZKRVH))9,(OOLSWDIRUDVWKPDPDLQWHQDQFHWKHUDS\LV
LQLWLDWHGDW9LVLWZLOOEHDVNHGWRUHDGWKHLQIRUPDWLRQOHDIOHWDQGZLOOEHLQVWUXFWHGE\
WKHLQYHVWLJDWRURQWKHSURSHUXVHRI(OOLSWD(DFKVXEMHFWZKRVHXVXDO,&6/$%$'3,
'LVNXVRU7XUEXKDOHUIRUDVWKPDPDLQWHQDQFHWKHUDS\LVLQLWLDWHGDW9LVLWZLOO
IROORZWKHVDPHSURFHGXUHUHDGLQJRIWKHLQIRUPDWLRQOHDIOHWGHPRQVWUDWLRQRIWKH
SURSHUXVHRIWKHLQKDOHUVE\WKH,QYHVWLJDWRUDQGWKHFRUUHFWGRVLQJ7KLVZLOOEH
IROORZHGE\DQLQKDODWLRQGHPRQVWUDWLRQE\WKHSDWLHQW$Q\PLVWDNHV7\SH$HUURUV
FRUUHVSRQGLQJWRFULWLFDOHUURUVDQGRYHUDOOHUURUVZLOOEHUHJLVWHUHGE\WKH,QYHVWLJDWRU
)RUWKHGHILQLWLRQRI7\SH$HUURUVDQGRYHUDOOHUURUVVHH6HFWLRQ
5DQGRPLVDWLRQDWWKLVYLVLWZLOO EHSHUIRUPHGRQDEDVLVWRWKH ))9,IL[HGGRVH
FRPELQDWLRQ GHOLYHUHG YLD (OOLSWD RU WKH LQLWLDWLRQ ZLWK XVXDO ,&6/$%$ LQKDODWLRQ
SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
98
$W:HHN 9LVLWDQGDW:HHN9LVLWVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXW
ZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQVHULRXVDGYHUVH
GUXJUHDFWLRQV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJ7\SH$
HUURUVDQGRYHUDOOHUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWDWURXJKSUHGRVH)(9ZLOOEH
DVVHVVHGE\WKH,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.DQGVXEMHFWVZLOODOVR
EHLQWHUYLHZHGDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRU
QRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVR
EHUHPLQGHGDERXWWKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHVZLOOEHFRQGXFWHGDWWKLVYLVLWDQG7\SH$HUURUVDQGRYHUDOOHUURUVZLWK
LQKDOHUZLOOEHUHFRUGHGIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWVXEMHFWVZLOODOVREHLQWHUYLHZHGDERXW
ZKHWKHUWKH\KDGH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJ
UHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKH
VDPHWLPHRIWKHGD\DV9LVLW
5HYLVHGWH[W
,Q DGGLWLRQ HDFK VXEMHFW ZKRVH ))9, (OOLSWD IRU DVWKPD PDLQWHQDQFH WKHUDS\ LV
LQLWLDWHGDW9LVLWZLOOEHDVNHGWRUHDGWKHLQIRUPDWLRQOHDIOHWDQGZLOOEHLQVWUXFWHGE\
WKHLQYHVWLJDWRURQWKHSURSHUXVHRI(OOLSWD(DFKVXEMHFWZKRVHXVXDO,&6/$%$'3,
'LVNXV RU7XUEXKDOHUIRUDVWKPDPDLQWHQDQFHWKHUDS\LVLQLWLDWHGDW9LVLWZLOOIROORZ
WKHVDPHSURFHGXUHUHDGLQJRIWKHLQIRUPDWLRQOHDIOHWGHPRQVWUDWLRQRIWKHSURSHUXVHRI
WKH LQKDOHUV E\ WKH ,QYHVWLJDWRU DQG WKH FRUUHFW GRVLQJ 7KLV ZLOO EH IROORZHG E\ DQ
LQKDODWLRQGHPRQVWUDWLRQE\WKHSDWLHQW$Q\FULWLFDOHUURUGHILQHGDVDQHUURUWKDWLV
PRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJLQKDOHGDQGRUQRQ
FULWLFDOHUURUZLOOEHUHJLVWHUHGE\WKH,QYHVWLJDWRU
5DQGRPLVDWLRQDWWKLV YLVLWZLOO EHSHUIRUPHGRQ D EDVLVWRWKH ))9,IL[HGGRVH
FRPELQDWLRQ GHOLYHUHG YLD (OOLSWD RU WKH LQLWLDWLRQ ZLWK XVXDO ,&6/$%$ LQKDODWLRQ
SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\
$W:HHN 9LVLWDQGDW:HHN9LVLWVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXW
ZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQVHULRXVDGYHUVH
GUXJUHDFWLRQV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
99
9LVLW:HHNVKRXOG EHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJFULWLFDODQG
QRQFULWLFDO HUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRIVWXG\
GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQ
FDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWDWURXJKSUHGRVH)(9ZLOOEHDVVHVVHG
E\WKH,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.DQGVXEMHFWVZLOODOVREH
LQWHUYLHZHGDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ
±VHULRXVDGYHUVHGUXJUHDFWLRQV)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREH
UHPLQGHGDERXWWKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHVZLOOEHFRQGXFWHGDWWKLVYLVLWDQGFULWLFDODQGQRQFULWLFDOHUURUV ZLWK
LQKDOHUZLOOEHUHFRUGHGIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWVXEMHFWVZLOODOVREHLQWHUYLHZHGDERXW
ZKHWKHUWKH\KDGH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJ
UHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKH
VDPHWLPHRIWKHGD\DV9LVLW
3URWRFROV\QRSVLVIRUVWXG\+=$$QDO\VLV
2ULJLQDOWH[W
7KH SULPDU\ HQGSRLQW LV GHILQHG DV WKH FKDQJH IURP EDVHOLQH LQ WKH $&7 WRWDO VFRUH
DVVHVVHGDW:HHN9LVLW7KHSULPDU\VHWRIDQDO\VLVLVWKH,77VHW
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHWZRVLGHGQRPLQDO
OHYHORIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,
WR,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
5HYLVHGWH[W
7KH SULPDU\ HQGSRLQW LV GHILQHG DV WKH FKDQJH IURP EDVHOLQH LQ WKH $&7 WRWDO VFRUH
DVVHVVHGDW:HHN9LVLW7KHSULPDU\VHWRIDQDO\VLVLVWKH,77VHW
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHWZRVLGHGQRPLQDO
OHYHORIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,
WR,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
(YHQ WKRXJK WKLV VWXG\ LV RSHQODEHO WKH WHDP ZLOO H[SORUH ZD\V WR HQVXUH VWXG\
EOLQG LV PDLQWDLQHG GXULQJ UHYLHZV RI WKH GDWD DQG SUHSURJUDPPLQJ SULRU WR
GDWDEDVHORFN0RUHLQIRUPDWLRQZLOOEHSURYLGHGLQWKH5$3

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
100
6HFWLRQ± 2YHUDOO'HVLJQ6FUHHQLQJUDQGRPLVDWLRQDQGIROORZXS
2ULJLQDOWH[W
$WWKH6FUHHQLQJ9LVLWHOLJLEOHVXEMHFWVZLOOEHFRQVHQWHGWRSDUWLFLSDWHWRWKHWULDODQG
SUHVFULEHGWKHQHFHVVDU\H[DPLQDWLRQV7KHVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWR
WKH$&7$VFUHHQLQJORJZLOOEHSHUIRUPHGDWWKLVYLVLW
$WDIXUWKHU YLVLWLH9'D\RFFXUULQJZLWKLQZHHNDIWHUWKHVFUHHQLQJYLVLW9
VXEMHFWVZKRPHHWDOORIWKH,QFOXVLRQ&ULWHULDQRQHRIWKH([FOXVLRQ&ULWHULDDQGZKR
DFFHSWWRJLYHWKHLUFRQVHQWZLOOEHUDQGRPLVHGLQWKHVWXG\5DQGRPLVDWLRQDWWKLVYLVLW
ZLOOEHRQDEDVLVWRWKH))9,IL[HGGRVHFRPELQDWLRQGHOLYHUHGE\(OOLSWD RUWRWKH
LQLWLDWLRQRI DQ\ XVXDO ,&6/$%$ '3, IRUDVWKPDPDLQWHQDQFHWKHUDS\FKRVHQE\WKH
SK\VLFLDQ 9LVLW  DQG 9LVLW  FDQ EH FRPELQHG LI WKH VXEMHFW GLG QRW WDNH KLV XVXDO
DVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG9LVLWDUHFRPELQHGWKHQWKLV
YLVLWZLOOEH'D\
$W9LVLW5DQGRPLVDWLRQYLVLW'D\EDVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGE\WKH
,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.$WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOG
EHSHUIRUPHGZLWKUHJLVWUDWLRQRIWKHEHVWYDOXH2QWKHPRUQLQJRI9LVLWVXEMHFWVZLOO
QRWWDNHWKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHG
KRXUVEHIRUHEDVHOLQHVSLURPHWU\
,QDGGLWLRQDW9LVLWVXEMHFWVZLOOEHDVNHGWRUHDGWKHZULWWHQ(OOLSWD SDFNDJHLQVHUWLI
UDQGRPLVHG LQWR WKH ))9, DUP RU 'LVNXV RU 7XUEXKDOHU LI UDQGRPLVHG LQ WKH XVXDO
,&6/$%$WKHUDS\DUPDQGZLOOEHLQVWUXFWHGE\WKHLQYHVWLJDWRURQWKHSURSHUXVHRI
LQKDOHUV 7KHQ WKH VXEMHFW ZLOO VHOIDGPLQLVWHU WKHLU ILUVW GRVH RI VWXG\ GUXJ XQGHU
VXSHUYLVLRQRI WKHLQYHVWLJDWRU $Q\PLVWDNHV7\SH$ HUURUV OLNHO\WR EHFULWLFDO DQG
RYHUDOOHUURUV ZLOO EH UHJLVWHUHGE\ WKHWUDLQHG +&3 $IWHU FRPSOHWLQJ WKHSURFHGXUH
VXEMHFWV ZLOO EH LQVWUXFWHG LQ WKH FRUUHFW XVH RI WKH GHYLFH E\ WKH WUDLQHG SK\VLFLDQ LI
QHHGHG7KHUHDIWHUHDFKVXEMHFWUDQGRPLVHGLQWRWKH))9,DUPZLOOEHLQVWUXFWHGWRVHOI
DGPLQLVWHURQHLQKDODWLRQZLWK(OOLSWD LQKDOHUHDFKGD\DWWKHVDPHWLPHRIWKHGD\DWD
WLPHWKDWLVFRQYHQLHQWIRUWKHVXEMHFW6XEMHFWUDQGRPLVHGLQWRXVXDO,&6/$%$WKHUDS\
DUP ZLOO EH LQVWUXFWHG WR VHOIDGPLQLVWHU WKH LQKDODWLRQ ZLWK 'LVNXV RU 7XUEXKDOHU
LQKDOHUWZLFHDGD\
6XEMHFWV ZLOO EH UHFRPPHQGHG WR XVH 6DOEXWDPRO DV QHHGHG WKURXJKRXW WKH VWXG\ IRU
UHOLHIRIWKHLUDVWKPDV\PSWRPV$W9LVLWUDQGRPLVDWLRQ'D\VXEMHFWZLOOEHDVNHG
WRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
$W :HHN  9LVLW  DQG DW :HHN  9LVLW  VXEMHFWV ZLOO EH WHOHSKRQHG E\ WKH
,QYHVWLJDWRU WR HQTXLUH DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ DGYHUVH HYHQWV
RQO\WKHVHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQVZLOOEHUHFRUGHGLQ
H&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRWWRVWXG\
WUHDWPHQW $W WKHVH WHOHSKRQH FDOOV VXEMHFWV ZLOO DOVR EH DVNHG WR FRPSOHWH WKH $&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
101
DQG 3$6$3 TXHVWLRQQDLUHV DQG WKH LQKDOHU XVH ZLOO EH DVVHVVHG E\ UHFRUGLQJ 7\SH $
HUURUVDQGRYHUDOOHUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ3UHGRVHWURXJK)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJWKHVSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPRO
ZLOOEHVWRSSHGKRXUVEHIRUHWKHVSLURPHWU\$WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOGEH
SHUIRUPHG ZLWK UHJLVWUDWLRQ RI WKH EHVW YDOXH $W WKLV YLVLW VXEMHFWV ZLOO DOVR EH
LQWHUYLHZHGE\WKH,QYHVWLJDWRUDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVH
HYHQWV RQO\ WKH VHULRXV DGYHUVH HYHQWV RU QRQ±VHULRXV DGYHUVH GUXJ UHDFWLRQV ZLOO EH
UHFRUGHGLQH&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRW
WRVWXG\WUHDWPHQW)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREHUHPLQGHGDERXW
WKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHV ZLOO EH FRQGXFWHG DW WKLV YLVLW DQG WKH LQKDOHU XVH ZLOO EH DVVHVVHG E\
UHFRUGLQJ 7\SH $ HUURUV DQG RYHUDOO HUURUV IROORZLQJ WKH QH[W SURFHGXUH VHOI
DGPLQLVWUDWLRQ RI RQH GRVH RI VWXG\ GUXJ E\ VXEMHFW HUURUV DVVHVVPHQW E\ WKH
LQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ
6XEMHFWV ZLOO EH LQWHUYLHZHG DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ VHULRXV
DGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWR
PDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKHVDPHWLPHRIWKHGD\DV9LVLW
5HYLVHGWH[W
$WWKH6FUHHQLQJ9LVLWHOLJLEOHVXEMHFWVZLOOEHFRQVHQWHGWRSDUWLFLSDWHWRWKHWULDODQG
SUHVFULEHGWKHQHFHVVDU\H[DPLQDWLRQV7KHVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWR
WKH$&7$VFUHHQLQJORJZLOOEHSHUIRUPHGDWWKLVYLVLW
$WDIXUWKHUYLVLWLH9'D\RFFXUULQJZLWKLQZHHNDIWHUWKHVFUHHQLQJYLVLW9
VXEMHFWVZKRPHHWDOO RIWKH,QFOXVLRQ&ULWHULDQRQHRIWKH([FOXVLRQ&ULWHULDDQGZKR
DFFHSWWRJLYHWKHLUFRQVHQWZLOOEHUDQGRPLVHGLQWKHVWXG\5DQGRPLVDWLRQDWWKLVYLVLW
ZLOOEHRQDEDVLVWRWKH))9,IL[HGGRVHFRPELQDWLRQGHOLYHUHGE\(OOLSWD RUWRWKH
LQLWLDWLRQ RI WKH XVXDO ,&6/$%$ '3, IRU DVWKPD PDLQWHQDQFH WKHUDS\ FKRVHQ E\ WKH
SK\VLFLDQ 9LVLW  DQG 9LVLW  FDQ EH FRPELQHG LI WKH VXEMHFW GLG QRW WDNH KLV XVXDO
DVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG9LVLWDUHFRPELQHGWKHQWKLV
YLVLWZLOOEH'D\
$W9LVLW5DQGRPLVDWLRQYLVLW'D\EDVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGE\WKH
,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.$WOHDVWWKUHHDVVHVVPHQWVVKRXOGEH
SHUIRUPHGZLWK UHJLVWUDWLRQ RI WKHEHVWYDOXH$W OHDVWWZR RIWKHVSLURPHWU\ HIIRUWV
VKRXOGEHDFFHSWDEOHDQGUHSHDWDEOH2QWKHPRUQLQJRI9LVLWVXEMHFWVZLOOQRWWDNH
WKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHGKRXUV
EHIRUHEDVHOLQHVSLURPHWU\
,QDGGLWLRQDW9LVLWVXEMHFWVZLOOEHDVNHGWRUHDGWKHZULWWHQ(OOLSWD SDFNDJHLQVHUWLI
UDQGRPLVHG LQWR WKH ))9, DUP RU 'LVNXV RU 7XUEXKDOHU LI UDQGRPLVHG LQ WKH XVXDO
,&6/$%$WKHUDS\DUPDQGZLOOEHLQVWUXFWHGE\WKHLQYHVWLJDWRURQWKHSURSHUXVHRI
LQKDOHUV 7KHQ WKH VXEMHFW ZLOO VHOIDGPLQLVWHU WKHLU ILUVW GRVH RI VWXG\ GUXJ XQGHU

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
102
VXSHUYLVLRQRIWKHLQYHVWLJDWRU$Q\ FULWLFDO HUURUGHILQHG DV DQ HUURUWKDW LV PRVW
OLNHO\WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJLQKDOHGRUQRQFULWLFDOHUURU
ZLOOEHUHJLVWHUHGE\WKHWUDLQHG+&3$IWHUFRPSOHWLQJWKHSURFHGXUHVXEMHFWVZLOOEH
LQVWUXFWHGLQWKHFRUUHFWXVHRIWKHGHYLFHE\WKHWUDLQHGSK\VLFLDQLIQHHGHG7KHUHDIWHU
HDFK VXEMHFW UDQGRPLVHG LQWR WKH ))9, DUP ZLOO EH LQVWUXFWHG WR VHOIDGPLQLVWHU RQH
LQKDODWLRQZLWK(OOLSWD LQKDOHUHDFKGD\DWWKHVDPHWLPHRIWKHGD\DWDWLPHWKDWLV
FRQYHQLHQWIRUWKHVXEMHFW6XEMHFWUDQGRPLVHGLQWRXVXDO,&6/$%$WKHUDS\DUPZLOOEH
LQVWUXFWHGWRVHOIDGPLQLVWHUWKHLQKDODWLRQZLWK'LVNXV RU7XUEXKDOHULQKDOHUWZLFHD
GD\
6XEMHFWV ZLOO EH UHFRPPHQGHG WR XVH 6DOEXWDPRO DV QHHGHG WKURXJKRXW WKH VWXG\ IRU
UHOLHIRIWKHLUDVWKPDV\PSWRPV$W9LVLWUDQGRPLVDWLRQ'D\VXEMHFWZLOOEHDVNHG
WRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
$W :HHN  9LVLW  DQG DW :HHN  9LVLW  VXEMHFWV ZLOO EH WHOHSKRQHG E\ WKH
,QYHVWLJDWRU WR HQTXLUH DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ DGYHUVH HYHQWV
RQO\WKHVHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQVZLOOEHUHFRUGHGLQ
H&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRWWRVWXG\
WUHDWPHQW $W WKHVH WHOHSKRQH FDOOV VXEMHFWV ZLOO DOVR EH DVNHG WR FRPSOHWH WKH $&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJFULWLFDODQG
QRQFULWLFDO HUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRIVWXG\
GUXJ HUURUV DVVHVVPHQW E\ WKH LQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVH RILQKDOHULQ
FDVHRIPXOWLSOHHUURUVGHWHFWLRQ3UHGRVHWURXJK)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJWKHVSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPRO
ZLOOEHVWRSSHGKRXUVEHIRUHWKHVSLURPHWU\$WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOGEH
SHUIRUPHG ZLWK UHJLVWUDWLRQ RI WKH EHVW YDOXH $W WKLV YLVLW VXEMHFWV ZLOO DOVR EH
LQWHUYLHZHGE\WKH,QYHVWLJDWRUDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVH
HYHQWV RQO\ WKH VHULRXV DGYHUVH HYHQWV RU QRQ±VHULRXV DGYHUVH GUXJ UHDFWLRQV ZLOO EH
UHFRUGHGLQH&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRW
WRVWXG\WUHDWPHQW)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREHUHPLQGHGDERXW
WKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHV ZLOO EH FRQGXFWHG DW WKLV YLVLW DQG WKH LQKDOHU XVH ZLOO EH DVVHVVHG E\
UHFRUGLQJ FULWLFDO DQG QRQFULWLFDO
HUURUV IROORZLQJ WKH QH[W SURFHGXUH VHOI
DGPLQLVWUDWLRQ RI RQH GRVH RI VWXG\ GUXJ E\ VXEMHFW HUURUV DVVHVVPHQW E\ WKH
LQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ
6XEMHFWV ZLOO EH LQWHUYLHZHG DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ VHULRXV
DGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWR
PDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKHVDPHWLPHRIWKHGD\DV9LVLW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
103
6HFWLRQ± 2YHUDOO'HVLJQ&ROOHFWHGGDWD
2ULJLQDOWH[W
(OLJLEOHVXEMHFWVZLOOFRPSOHWHWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
DW5DQGRPLVDWLRQ9LVLW9LVLW'D\DQGDW9LVLW:HHNRUDWWKH(DUO\
:LWKGUDZDOYLVLW$&7TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRE\WKHVXEMHFWDW6FUHHQLQJ
YLVLW9LVLW:HHNSKRQHFDOORU9LVLWDW:HHN 9LVLWDQG:HHNSKRQH
FDOORU9LVLW0$56$TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRDW:HHN9LVLW
,QKDOHUXVHDVVHVVPHQWZLOOEHSHUIRUPHGDW5DQGRPLVDWLRQ9LVLW9LVLW'D\DW
:HHN9LVLWDQGDW:HHN9LVLW(DUO\:LWKGUDZDOYLVLWE\UHFRUGLQJWKH
7\SH$HUURUVDQGWKHRYHUDOO HUURUV3DWLHQW¶VVDWLVIDFWLRQDQGSUHIHUHQFH3$6$34
ZLOOEHHYDOXDWHGDW:HHN9LVLW
5HYLVHGWH[W
(OLJLEOHVXEMHFWVZLOOFRPSOHWHWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
DW 5DQGRPLVDWLRQ 9LVLW 9LVLW  'D\  DQG DW 9LVLW  :HHN  RU DW WKH (DUO\
:LWKGUDZDOYLVLW$&7TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRE\WKHVXEMHFWDW6FUHHQLQJ
YLVLW9LVLW:HHNSKRQHFDOORU9LVLWDW:HHN9LVLWDQG:HHNSKRQH
FDOORU9LVLW0$56$TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRDW:HHN9LVLW
,QKDOHU XVH DVVHVVPHQW ZLOO EH SHUIRUPHG DW 5DQGRPLVDWLRQ 9LVLW 9LVLW  'D\  DW
:HHN9LVLWDQGDW:HHN9LVLW(DUO\:LWKGUDZDOYLVLWE\UHFRUGLQJWKH
FULWLFDODQGQRQFULWLFDOHUURUV3DWLHQW¶VVDWLVIDFWLRQDQGSUHIHUHQFH3$6$34ZLOOEH
HYDOXDWHGDW:HHN9LVLW
6HFWLRQ± 7\SHDQG1XPEHURI6XEMHFWV
2ULJLQDOWH[W
6XEMHFWV ZLWK GRFXPHQWHG SK\VLFLDQ¶V GLDJQRVLV RI DVWKPD   \HDU XQVDWLVIDFWRULO\
FRQWUROOHG DVWKPD $&7   WUHDWHG E\ ,&6 DORQH DQG LQWHQGHG WR EH WUHDWHG E\
,&6/$%$ PDLQWHQDQFH WKHUDS\ $ VXEMHFW ZLOO EH HOLJLEOH IRU LQFOXVLRQ LQ WKLV VWXG\
RQO\LIHLWKHUDIILOLDWHGWRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDRIVFUHHQIDLOXUHVXEMHFWVZLOOKDYHWREHVFUHHQHGLQWKH VWXG\ZLWK
VXEMHFWVFHQWHU
5HYLVHGWH[W
6XEMHFWV ZLWK GRFXPHQWHG SK\VLFLDQ¶V GLDJQRVLV RI DVWKPD   \HDU XQVDWLVIDFWRULO\
FRQWUROOHG DVWKPD $&7   WUHDWHG E\ ,&6 DORQH DQG LQWHQGHG WR EH WUHDWHG E\
,&6/$%$ PDLQWHQDQFH WKHUDS\ $ VXEMHFW ZLOO EH HOLJLEOH IRU LQFOXVLRQ LQ WKLV VWXG\
RQO\LIHLWKHUDIILOLDWHGWRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
104
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDW OHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDVFUHHQIDLOXUHUDWHDSSUR[LPDWHO\ VXEMHFWVZLOOKDYHWREH
VFUHHQHGLQWKHVWXG\ZLWKVXEMHFWVFHQWHU
6HFWLRQ± 5LVN$VVHVVPHQW
2ULJLQDOWH[W
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
+\SHUVHQVLWLYLW\
7KHUHSRUWHG
K\SHUVHQVLWLYLW\HYHQWVLQ
FOLQLFDOWULDOVZHUHQRW
JHQHUDOO\VHULRXVGLGQRW
OHDGWRGLVFRQWLQXDWLRQLQ
WKHVWXGLHVDQGZHUH
XVXDOO\FRQIRXQGHGE\
HLWKHUWKHVXEMHFW¶VPHGLFDO
FRQGLWLRQVXFKDV&23'
RURWKHUIDFWRUVDWWKHWLPH
RIWKHHYHQW
,QVSRQWDQHRXVGDWD
V\PSWRPVRI
K\SHUVHQVLWLYLW\UDQJHG
IURPPLOGUDVKDQGSUXULWLV
WRVHYHUHJHQHUDOLVHGUDVK
DQGHU\WKHPDDQGVHYHUH
FDVHVLQYROYLQJDQJLRGHPD
RIWKHIDFHODU\Q[DQG
SKDU\Q[
7KHVHHYHQWVZHUHUDUH
6XEMHFWV ZLWK D KLVWRU\ RI
DGYHUVH UHDFWLRQ LQFOXGLQJ
LPPHGLDWH
RU
GHOD\HG
K\SHUVHQVLWLYLW\
WR
DQ\
LQWUDQDVDO
LQKDOHG
RU
V\VWHPLF FRUWLFRVWHURLG DQG
/$%$
WKHUDS\
DQG
WR
FRPSRQHQWV
RI
WKH
LQKDODWLRQ
SRZGHU
HJ
ODFWRVH
PDJQHVLXP
VWHDUDWH
,Q
DGGLWLRQ
VXEMHFWV ZLWK D KLVWRU\ RI
VHYHUH PLON SURWHLQ DOOHUJ\
WKDW LQ WKH RSLQLRQ RI WKH
,QYHVWLJDWRUFRQWUDLQGLFDWHV
WKH VXEMHFW¶V SDUWLFLSDWLRQ
ZLOODOVREHH[FOXGHG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
105
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
6\VWHPLFHIIHFWVRI
FRUWLFRVWHURLGVDGUHQDO
VXSSUHVVLRQH\HGLVRUGHUV
GHFUHDVHGERQHGHQVLW\DQG
DVVRFLDWHGIUDFWXUHV
$GUHQDOVXSSUHVVLRQLVD
NQRZQFODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
VWXGLHVVKRZHGWKDW))
HIIHFWVDUHFRPSDUDEOHZLWK
RWKHUFRUWLFRVWHURLGV1R
VWXGLHVKDYHVKRZQD
FOLQLFDOO\UHOHYDQWHIIHFWRI
))9,RQWKHK\SRWKDODPLF
SLWXLWDU\D[LV+3$7KLV
LQFOXGHVDIRUPDO+3$
VWXG\+=$XVLQJ
KRXUVHUXPFRUWLVRO
PHDVXUHPHQWVDQGPXOWLSOH
VWXGLHVZLWK&23'DQG
DVWKPDVXEMHFWVZKLFK
PRQLWRUHGXULQDU\FRUWLVRO
'XULQJFOLQLFDO
GHYHORSPHQWQRHYHQWVRI
$GUHQDO6XSSUHVVLRQZHUH
UHSRUWHG
(\HGLVRUGHUVDUHDNQRZQ
FODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
VWXGLHVVKRZHG))DWKLJK
GRVHFRPSDUDEOHWRRWKHU
KLJKGRVHFRUWLFRVWHURLGV,Q
VWXG\+=$))9,
))DQG)3LQVXEMHFWVZLWK
DVWKPD
IRUPDORSKWKDOPLF
DVVHVVPHQWVZHUHFRQGXFWHG
LQFOXGLQJ/2&6,,,
HYDOXDWLRQVIRURFXODU
RSDFLWLHVWKURXJKRXWWKH
VWXG\7KLVVWXG\VKRZHG
QRDSSDUHQWHIIHFWVRQOHQV
RSDFLILFDWLRQFRPSDUHGWR
EDVHOLQH'XULQJVWXGLHVLQ
ERWKVXEMHFWVZLWKDVWKPD
DQG&23'QRDVVRFLDWHG
DIIHFWRQRFXODUGLVRUGHUV
7KHPLWLJDWLRQLQWKLVVWXG\
IRU DOO V\VWHPLF HIIHFWV RI
FRUWLFRVWHURLGV
LV
WKDW
FKURQLF XVHUV RI V\VWHPLF
FRUWLFRVWHURLGVDUHH[FOXGHG
IURP WKLV VWXG\ D VXEMHFW
ZKR LQ WKH RSLQLRQ RI WKH
,QYHVWLJDWRU LV FRQVLGHUHG
WR EH D FKURQLF XVHU RI
V\VWHPLF FRUWLFRVWHURLGV IRU
UHVSLUDWRU\
RU
RWKHU
LQGLFDWLRQV
LI
XQVXUH
GLVFXVV ZLWK WKH PHGLFDO
PRQLWRUSULRUWRVFUHHQLQJ

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
106
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
ZDVREVHUYHG
'HFUHDVHGERQHGHQVLW\LVD
GRZQFODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
GDWDVKRZHGWKDWKLJKGRVH
FRUWLFRVWHURLGHIIHFWVRI))
ZHUHFRPSDUDEOHWRRWKHU
FRQUWLFRVWHURLGV3DWLHQWV
ZLWK$VWKPD,QDQ
LQWHJUDWHGDQDO\VLVRI
VWXGLHVLQDVWKPD
SDWLHQWVWKHLQFLGHQFHRI
IUDFWXUHVZLWK))9,ZDV
 DQGXVXDOO\
DVVRFLDWHGZLWKWUDXPD
5HYLVHGWH[W
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
+\SHUVHQVLWLYLW\
7KHUHSRUWHG
K\SHUVHQVLWLYLW\HYHQWVLQ
FOLQLFDOWULDOVZHUHQRW
JHQHUDOO\VHULRXVGLGQRW
OHDGWRGLVFRQWLQXDWLRQLQ
WKHVWXGLHVDQGZHUH
XVXDOO\FRQIRXQGHGE\
HLWKHUWKHVXEMHFW¶VPHGLFDO
FRQGLWLRQVXFKDV&23'
RURWKHUIDFWRUVDWWKHWLPH
RIWKHHYHQW
,QVSRQWDQHRXVGDWD
V\PSWRPVRI
K\SHUVHQVLWLYLW\UDQJHG
IURPPLOGUDVKDQGSUXULWLV
6XEMHFWV ZLWK D KLVWRU\ RI
DGYHUVH UHDFWLRQ LQFOXGLQJ
LPPHGLDWH
RU
GHOD\HG
K\SHUVHQVLWLYLW\
WR
DQ\
LQWUDQDVDO
LQKDOHG
RU
V\VWHPLF FRUWLFRVWHURLG DQG
/$%$
WKHUDS\
DQG
WR
FRPSRQHQWV
RI
WKH
LQKDODWLRQ
SRZGHU
HJ
ODFWRVH
PDJQHVLXP
VWHDUDWH ZLOO EH H[FOXGHG
,Q DGGLWLRQVXEMHFWVZLWKD
KLVWRU\
RI
VHYHUH
PLON
SURWHLQ DOOHUJ\ WKDW LQ WKH
RSLQLRQ RI WKH ,QYHVWLJDWRU
FRQWUDLQGLFDWHVWKHVXEMHFW¶V

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
107
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
WRVHYHUHJHQHUDOLVHGUDVK
DQGHU\WKHPDDQGVHYHUH
FDVHVLQYROYLQJDQJLRGHPD
RIWKHIDFHODU\Q[DQG
SKDU\Q[
7KHVHHYHQWVZHUHUDUH
SDUWLFLSDWLRQ ZLOO DOVR EH
H[FOXGHG
6\VWHPLFHIIHFWVRI
FRUWLFRVWHURLGVDGUHQDO
VXSSUHVVLRQH\HGLVRUGHUV
GHFUHDVHGERQHGHQVLW\DQG
DVVRFLDWHGIUDFWXUHV
$GUHQDOVXSSUHVVLRQLVD
NQRZQFODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
VWXGLHVVKRZHGWKDW))
HIIHFWVDUHFRPSDUDEOHZLWK
RWKHUFRUWLFRVWHURLGV1R
VWXGLHVKDYHVKRZQD
FOLQLFDOO\UHOHYDQWHIIHFWRI
))9,RQWKHK\SRWKDODPLF
SLWXLWDU\D[LV+3$7KLV
LQFOXGHVDIRUPDO+3$
VWXG\+=$XVLQJ
KRXUVHUXPFRUWLVRO
PHDVXUHPHQWVDQGPXOWLSOH
VWXGLHVZLWK&23'DQG
DVWKPDVXEMHFWVZKLFK
PRQLWRUHGXULQDU\FRUWLVRO
'XULQJFOLQLFDO
GHYHORSPHQWQRHYHQWVRI
$GUHQDO6XSSUHVVLRQZHUH
UHSRUWHG
(\HGLVRUGHUVDUHDNQRZQ
FODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
VWXGLHVVKRZHG))DWKLJK
GRVHFRPSDUDEOHWRRWKHU
KLJKGRVHFRUWLFRVWHURLGV,Q
VWXG\+=$))9,
))DQG)3LQVXEMHFWVZLWK
DVWKPD
IRUPDORSKWKDOPLF
DVVHVVPHQWVZHUHFRQGXFWHG
LQFOXGLQJ/2&6,,,
HYDOXDWLRQVIRURFXODU
7KHPLWLJDWLRQLQWKLVVWXG\
IRU DOO V\VWHPLF HIIHFWV RI
FRUWLFRVWHURLGV
LV
WKDW
FKURQLF XVHUV RI V\VWHPLF
FRUWLFRVWHURLGVDUHH[FOXGHG
IURP WKLV VWXG\ D VXEMHFW
ZKR LQ WKH RSLQLRQ RI WKH
,QYHVWLJDWRU LV FRQVLGHUHG
WR EH D FKURQLF XVHU RI
V\VWHPLF FRUWLFRVWHURLGV IRU
UHVSLUDWRU\
RU
RWKHU
LQGLFDWLRQV
LI
XQVXUH
GLVFXVV ZLWK WKH PHGLFDO
PRQLWRU SULRU WR VFUHHQLQJ
ZLOOEHH[FOXGHG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
108
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
RSDFLWLHVWKURXJKRXWWKH
VWXG\7KLVVWXG\VKRZHG
QRDSSDUHQWHIIHFWVRQOHQV
RSDFLILFDWLRQFRPSDUHGWR
EDVHOLQH'XULQJVWXGLHVLQ
ERWKVXEMHFWVZLWKDVWKPD
DQG&23'QRDVVRFLDWHG
DIIHFWRQRFXODUGLVRUGHUV
ZDVREVHUYHG
'HFUHDVHGERQHGHQVLW\LVD
NQRZQ FODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
GDWDVKRZHGWKDWKLJKGRVH
FRUWLFRVWHURLGHIIHFWVRI))
ZHUHFRPSDUDEOHWRRWKHU
FRQUWLFRVWHURLGV3DWLHQWV
ZLWK$VWKPD,QDQ
LQWHJUDWHGDQDO\VLVRI
VWXGLHVLQDVWKPD
SDWLHQWVWKHLQFLGHQFHRI
IUDFWXUHVZLWK))9,ZDV
 DQGXVXDOO\
DVVRFLDWHGZLWKWUDXPD
6HFWLRQ± 6FUHHQLQJ%DVHOLQH)DLOXUHV
2ULJLQDOWH[W
$WRWDORIVXEMHFWVZLOOEHVFUHHQHGDVVXEMHFWVDUHSODQQHGWREHUDQGRPLVHGDQG
RIVFUHHQIDLOXUHLVH[SHFWHG
5HYLVHGWH[W
$SSUR[LPDWHO\  VXEMHFWV ZLOO EH VFUHHQHG DV  VXEMHFWV DUH SODQQHG WR EH
UDQGRPLVHGDQGD RIVFUHHQIDLOXUHUDWH LVH[SHFWHG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
109
6HFWLRQ± 3UHSDUDWLRQ+DQGOLQJ6WRUDJH$FFRXQWDELOLW\
2ULJLQDOWH[W
$OO))9, DQGFRPSDUDWLYH,&6/$%$PDLQWHQDQFHWKHUDS\SUHVFULEHGWKURXJKRXWWKH
VWXG\ZLOOEHGLVSHQVHGDWDQGFROOHFWHG IURPWKHLQYHVWLJDWRUVLWH
,QYHVWLJDWLRQDOSURGXFWPXVWEHVWRUHGLQDVHFXUHDUHDXQGHUWKHDSSURSULDWHSK\VLFDO
FRQGLWLRQVIRUWKHSURGXFW$OO'3,VFRQWDLQLQJ))9,PXVWEHVWRUHGDWDWHPSHUDWXUHRI
XSWR&%XGHVRQLGH)RUPRWHURODQG)OXWLFDVRQH3URSLRQDWH6DOPHWHURO'3,VPXVWEH
VWRUHGDWDWHPSHUDWXUHRIXSWR&
5HYLVHGWH[W
$OO))9, DQGFRPSDUDWLYH,&6/$%$PDLQWHQDQFHWKHUDS\SUHVFULEHGWKURXJKRXWWKH
VWXG\ZLOOEHGLVSHQVHGDWDQGFROOHFWHGIURPWKHLQYHVWLJDWRUVLWH
,QYHVWLJDWLRQDOSURGXFWPXVWEHVWRUHGLQDVHFXUHDUHDXQGHUWKHDSSURSULDWHSK\VLFDO
FRQGLWLRQVIRUWKHSURGXFW$OO'3,VFRQWDLQLQJ))9,PXVWEHVWRUHGDWDWHPSHUDWXUHRI
XSWR&%XGHVRQLGH)RUPRWHURO'3,VPXVWEHVWRUHGDWDWHPSHUDWXUHRIXSWR&
DQG)OXWLFDVRQH3URSLRQDWH6DOPHWHURO'3,VVWRUHGDW#&
6HFWLRQ± ,QYHVWLJDWLRQDO3URGXFW0DOIXQFWLRQ
1HZ7H[W
$Q\LQYHVWLJDWLRQDOSURGXFWLQKDOHUWKDWIDLOVWRIXQFWLRQSURSHUO\PXVWEHLGHQWLILHG
WR*6.SHUVRQQHO'HWDLOVRIWKHIDLOXUHZLOOEHGRFXPHQWHGLQWKHH&5)(OOLSWD
LQKDOHUVZLOOEHUHWXUQHGWR*6.IRUWHVWLQJ7KHVXEMHFWVKRXOGUHWXUQWKHLQKDOHU
WRWKHFOLQLFDVVRRQDVSRVVLEOHWRDYRLGPLVVLQJDQ\GRVHV7KHVLWHZLOOWKHQFRQWDFW
*6.¶VLQWHUQDO,:56DOVRNQRZQDVWKH5HJLVWUDWLRQDQG0HGLFDWLRQ2UGHULQJ
6\VWHP>5$026@1* DQGREWDLQDQHZWUHDWPHQWSDFNQXPEHUIRUWKLVVXEMHFW
DQGGLVSHQVHDQHZVWXG\PHGLFDWLRQNLWIURPWKHVLWH
VLQYHVWLJDWLRQDOSURGXFW
VXSSO\DVLQVWUXFWHGSHUWKH,:56

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
110
6HFWLRQ± 7LPHDQG(YHQWV7DEOH
2ULJLQDOWDEOH
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone 
call 1
Visit 
4**
Visit 5
Phone 
call 2
Visit 6
Early 
Withdrawal
Study week (± specified 
no. of days)
'D\WR

'D\
:HHN
 
GD\V
:HHN


GD\V
:HHN
 
GD\V
:HHN


GD\V
Early 
Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
Assessments
,QIRUPHG&RQVHQW
x
(OLJLELOLW\FULWHULD
x
x
'HPRJUDSK\
x
6PRNLQJVWDWXV
x
0HGLFDO)DPLO\ KLVWRU\ RI
FRQVHQWHGVXEMHFWVLQFOXGLQJ
&9
5LVN
IDFWRUV
DQG
H[DFHUEDWLRQKLVWRU\
x
3*[VDOLYDVDPSOH
x
3K\VLFDOH[DPLQDWLRQ
x
x
x
x
x
Safety Assessments
8ULQH3UHJQDQF\7HVW
x
x
x
x
([DFHUEDWLRQ$VVHVVPHQW
x
x
x
x
x
x
9LWDOVLJQV
x
x
x
x
x
6HULRXV $GYHUVH (YHQW DQG
$GYHUVH
'UXJ
5HDFWLRQ
$VVHVVPHQW
x
x
x
x
x
x
Efficacy Assessments
6SLURPHWU\
7HVWLQJ
3UH
GRVHWURXJK)(9
x
x
x 
Subject Questionnaires 
$VWKPD&RQWURO7HVW
x
x
x
x
x
x
x
(4'
x
x
x
$VWKPD4XDOLW\RI
/LIH4XHVWLRQQDLUH
x
x
x
0$56$TXHVWLRQQDLUH
x
x
x
x
3DWLHQW
6DWLVIDFWLRQ
DQG
3UHIHUHQFH3$6$34
x
x
Inhaler 
correct 
use 
assessment
7\SH$RYHUDOOHUURUVUHFRUG
x
x
x
Medication Assessments
&RQFRPLWDQW
0HGLFDWLRQ
$VVHVVPHQW
x
x
x
x
x
'LVSHQVH6WXG\0HGLFDWLRQð
x
x
&ROOHFW6WXG\0HGLFDWLRQð
x
x
x
RAMOS/eCRF
5$0261*
x
x
H&5)
x
x
x
x
x
x
x

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
111

6$(DQG$'5PRQLWRULQJZLOORFFXUIURP'D\6$(UHODWHGWRVWXG\SDUWLFLSDWLRQVKRXOGEHJLQIURPVLJQLQJRI
,&)$QDGGLWLRQDOVDIHW\DQG$&7FKHFNLVSURYLGHGE\SKRQHDWZHHNDQG

7KURXJKRXWWKHVWXG\WKHVWXG\PHGLFDWLRQZLOOEHGLVSHQVHGDQGFROOHFWHGE\WKHLQYHVWLJDWRUVLWH
9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLVXVXDODVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH
7KHQWKLVYLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEHFROOHFWHGDWWKLVYLVLW:ULWWHQ,QIRUPHG&RQVHQWPXVW
EHREWDLQHGSULRUWRLQLWLDWLRQRIVWXG\SURFHGXUHVRULQLWLDWLQJFKDQJHVLQPHGLFDWLRQV
 9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW 5DQGRPLVDWLRQYLVLW
3*[VDOLYDVDPSOHFROOHFWHGDW9LVLW5DQGRPLVDWLRQRUDQ\VFKHGXOHGFOLQLFYLVLWWKHUHDIWHU
2QO\LIHDUO\ZLWKGUDZDORFFXUVEHIRUH:HHN
 2QO\IRUFKLOGEHDULQJZRPHQ
5HYLVHGWDEOH
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone 
call 1
Visit 
4**
Visit 5
Phone 
call 2
Visit 6
Early 
Withdrawal
Study week (± specified 
no. of days)
'D\WR

'D\
:HHN
 
GD\V
:HHN


GD\V
:HHN
 
GD\V
:HHN


GD\V
Early 
Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
Assessments
,QIRUPHG&RQVHQW
x
(OLJLELOLW\FULWHULD
x
x
'HPRJUDSK\
x
6PRNLQJVWDWXV
x
0HGLFDO)DPLO\ KLVWRU\ RI
FRQVHQWHGVXEMHFWVLQFOXGLQJ
&9
5LVN
IDFWRUV
DQG
H[DFHUEDWLRQKLVWRU\
x
3*[VDOLYDVDPSOH
x
3K\VLFDOH[DPLQDWLRQ
x
x
x
x
x
Safety Assessments
8ULQH3UHJQDQF\7HVW
x
x
x
x
([DFHUEDWLRQ$VVHVVPHQW
x
x
x
x
x
x
9LWDOVLJQV
x
x
x
x
x
6HULRXV $GYHUVH (YHQW DQG
$GYHUVH
'UXJ
5HDFWLRQ
$VVHVVPHQW
x
x
x
x
x
x
Efficacy Assessments
6SLURPHWU\
7HVWLQJ
3UH
GRVHWURXJK)(9
x
x
x 
Subject Questionnaires 
$VWKPD&RQWURO7HVW
x
x
x
x
x
x
x
(4'
x
x
x
$VWKPD4XDOLW\RI
/LIH4XHVWLRQQDLUH
x
x
x
0$56$TXHVWLRQQDLUH
x
x
x
x
3DWLHQW
6DWLVIDFWLRQ
DQG
3UHIHUHQFH3$6$34
x
x
Inhaler 
correct 
use 
assessment

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
112
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone 
call 1
Visit 
4**
Visit 5
Phone 
call 2
Visit 6
Early 
Withdrawal
Study week (± specified 
no. of days)
'D\WR

'D\
:HHN
 
GD\V
:HHN


GD\V
:HHN
 
GD\V
:HHN


GD\V
Early 
Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
Critical and non-critical 
errors record
x
x
x
Medication Assessments
&RQFRPLWDQW
0HGLFDWLRQ
$VVHVVPHQW
x
x
x
x
x
'LVSHQVH6WXG\0HGLFDWLRQð
x
x
&ROOHFW6WXG\0HGLFDWLRQð
x
x
x
RAMOS/eCRF
5$0261*
x
x
H&5)
x
x
x
x
x
x
x

6$(DQG$'5PRQLWRULQJZLOORFFXUIURP'D\6$(UHODWHGWRVWXG\SDUWLFLSDWLRQVKRXOGEHJLQIURPVLJQLQJRI
,&)$QDGGLWLRQDOVDIHW\DQG$&7FKHFNLVSURYLGHGE\SKRQHDWZHHNDQG

7KURXJKRXWWKHVWXG\WKHVWXG\PHGLFDWLRQZLOOEHGLVSHQVHGDQGFROOHFWHGE\WKHLQYHVWLJDWRUVLWH
9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLVXVXDODVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH
7KHQWKLVYLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEHFROOHFWHGDWWKLVYLVLW:ULWWHQ,QIRUPHG&RQVHQWPXVW
EHREWDLQHGSULRUWRLQLWLDWLRQRIVWXG\SURFHGXUHVRULQLWLDWLQJFKDQJHVLQPHGLFDWLRQV
 9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW 5DQGRPLVDWLRQYLVLW
3*[VDOLYDVDPSOHFROOHFWHGDW9LVLW5DQGRPLVDWLRQRUDQ\VFKHGXOHGFOLQLFYLVLWWKHUHDIWHU
2QO\LIHDUO\ZLWKGUDZDORFFXUVEHIRUH:HHN
2QO\IRUFKLOGEHDULQJZRPHQ
Note: All adverse events will be recorded in the source documents but only information regarding non-serious 
adverse drug reactions (ADRs) and serious adverse events (SAEs) will be documented and reported in the 
eCRF.
6HFWLRQ,QKDOHU&RUUHFW8VH$VVHVVPHQW
2ULJLQDOWH[W
&RUUHFWXVHRIWKHLQKDOHUZLOOEHDVVHVVHGDVRXWOLQHGLQWKH7LPHDQG(YHQWV7DEOH
6HFWLRQ
7DEOH
/LVWRI7\SH$OLNHO\WREHFULWLFDODQGRYHUDOOHUURUV IRU(OOLSWD70
7\SH$HUURUV IRU(OOLSWD70
\HV
QR
2YHUDOOHUURUV IRU(OOLSWD70
\HV
QR
)DLOHGWRRSHQFRYHU
1R
H[KDODWLRQ
EHIRUH
DQ
LQKDOLQJ
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
%ORFNHG
DLU
LQOHW
GXULQJ
LQKDODWLRQPDQRHXYUH
6KRRNWKHGHYLFHXSVLGHGRZQDIWHU
GRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUH

ORQJ

VWHDG\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
113
7\SH$HUURUV IRU(OOLSWD70
\HV
QR
2YHUDOOHUURUV IRU(OOLSWD70
\HV
QR

GHHS
,QKDODWLRQ IURP PRXWKSLHFH NHSW
EHWZHHQOLSV
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
'LGQRWKROGEUHDWK
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHH
WH[WER[@
7DEOH
/LVW7\SH$OLNHO\WREHFULWLFDODQGRYHUDOOHUURUV IRU'LVNXV70
7\SH$HUURUVIRU'LVNXV70
\HV
QR
2YHUDOOHUURUVIRU'LVNXV70
\HV
QR
)DLOHGWRRSHQFRYHU
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
/HYHULVQRWSXVKHGEDFN
,QKDODWLRQPDQRHXYUH

VWHDG\

GHHS
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWKROGEUHDWK
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHH
WH[WER[@
7DEOH
/LVWRI7\SH$OLNHO\WREHFULWLFDOHUURUVDQGRYHUDOOHUURUV IRU
7XUEXKDOHU
7\SH$HUURUVIRU7XUEXKDOHU
\HV
QR
2YHUDOOHUURUVIRU
7XUEXKDOHU
\HV
QR
)DLOHGWRUHPRYHFDS
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
'LGQRWKROGGHYLFHXSULJKW
2.GXULQJGRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUH

IRUFHIXO

GHHS
1RWHWR+&3 LWLVLPSRUWDQW
WKDWWKHLQKDODWLRQLVIRUFHIXO

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
114
7\SH$HUURUVIRU7XUEXKDOHU
\HV
QR
2YHUDOOHUURUVIRU
7XUEXKDOHU
\HV
QR
DQGGHHSIURPWKHVWDUWIRU
WKLVLQKDOHU
%DVHQRWWZLVWHGIXOO\EDFNZDUGV
DQGIRUZDUGVQRFOLFNKHDUG
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
'LGQRWKROGEUHDWK
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
$Q\RWKHUFRPPHQWV>IUHH
WH[WER[@
5HYLVHGWH[W
&RUUHFWXVHRIWKHLQKDOHUZLOOEHDVVHVVHGDVRXWOLQHGLQWKH7LPHDQG(YHQWV7DEOH
6HFWLRQ
7DEOH
&ULWLFDODQG1RQFULWLFDOHUURUVIRU(OOLSWD70
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURULV
GHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDO
PHGLFDWLRQEHLQJLQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@1R
>@<HVLI\HVWLFNDSSURSULDWHRSWLRQVEHORZ
&ULWLFDO(UURUVIRU(OOLSWD70
\HV
QR
1RQFULWLFDO
(UURUV
IRU
(OOLSWD70
\HV
QR
)DLOHGWRRSHQFRYHU
1R
H[KDODWLRQ
EHIRUH
DQ
LQKDODWLRQ
6KRRN WKH GHYLFH XSVLGH GRZQ
DIWHUGRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUHZDV
QRW

ORQJ

VWHDG\

GHHS
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH

1RVHDOE\WKHOLSVDURXQGWKH
'LGQRWKROGEUHDWK

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
115
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUVIRU'LVNXV70
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURULV
GHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDO
PHGLFDWLRQEHLQJLQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@1R
>@<HVLI\HVWLFNDSSURSULDWHRSWLRQVEHORZ
&ULWLFDO(UURUVIRU'LVNXV70
\HV
QR
1RQFULWLFDO(UURUVIRU
'LVNXV70
\HV
QR
)DLOHGWRRSHQFRYHU
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
/HYHULVQRWSXVKHGEDFN
,QKDODWLRQPDQRHXYUHZDV
QRW

VWHDG\

GHHS
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
'LGQRWKROGEUHDWK
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
116
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUV IRU7XUEXKDOHU
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURU
LVGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDO
PHGLFDWLRQEHLQJLQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@1R
>@<HVLI\HVWLFNDSSURSULDWHRSWLRQVEHORZ
&ULWLFDO(UURUVIRU7XUEXKDOHU
\HV
QR
1RQFULWLFDO(UURUVIRU
7XUEXKDOHU
\HV
QR
)DLOHGWRUHPRYHFDS
'HYLFHWLSSHGGRZQZDUGV
DIWHUGRVHSUHSDUDWLRQ
'LGQRWKROGGHYLFHXSULJKW
2.GXULQJGRVHSUHSDUDWLRQ
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
%DVHQRWWZLVWHGIXOO\EDFNZDUGV
DQGIRUZDUGVQRFOLFNKHDUG
,QKDODWLRQPDQRHXYUHZDV
QRW

IRUFHIXO

GHHS
1RWHWR+&3 LWLVLPSRUWDQW
WKDWWKHLQKDODWLRQLVIRUFHIXO
DQGGHHSIURPWKHVWDUWIRU
WKLVLQKDOHU
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWKROGEUHDWK
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
117
6HFWLRQ7URXJKSUHGRVH)(9DVVHVVPHQW
2ULJLQDOWH[W
$OO VLWHV ZLOO XVH VWDQGDUGLVHG VSLURPHWU\ HTXLSPHQW SURYLGHG E\ *6. )RU HDFK
REVHUYDWLRQ DW OHDVW  YDOLG ZLWK QR PRUH WKDQ  HIIRUWV ZLOO EH REWDLQHG 7KH EHVW
)(9YDOXHZLOOEHUHFRUGHGLQWKHH&5)
5HYLVHGWH[W
$OO VLWHV ZLOO XVH VWDQGDUGLVHG VSLURPHWU\ HTXLSPHQW SURYLGHG E\ *6. )RU HDFK
REVHUYDWLRQDWOHDVWZLWKQRPRUHWKDQHIIRUWVZLOOEHREWDLQHG$WOHDVWWZRRIWKH
VSLURPHWU\HIIRUWVVKRXOGEHDFFHSWDEOHDQGUHSHDWDEOH 7KHEHVW)(9YDOXHZLOOEH
UHFRUGHGLQWKHH&5)
6HFWLRQ&OLQLFDO6DIHW\/DERUDWRU\$VVHVVPHQW
2ULJLQDOWH[W
$Q\ DEQRUPDO ODERUDWRU\ WHVW UHVXOWV KHPDWRORJ\ FOLQLFDO FKHPLVWU\ RU XULQDO\VLV RU
RWKHU VDIHW\ DVVHVVPHQWV HJ (&*V UDGLRORJLFDO VFDQV YLWDO VLJQV PHDVXUHPHQWV
LQFOXGLQJ WKRVH WKDW ZRUVHQ IURP EDVHOLQH DQG IHOW WR EH FOLQLFDOO\ VLJQLILFDQW LQ WKH
PHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKH ,QYHVWLJDWRUDUHWREHUHFRUGHGDVQRQVHULRXV
$'5VRU6$(VDVDSSURSULDWH
5HYLVHGWH[W
7KHUHDUHQRFOLQLFDOVDIHW\ODERUDWRU\DVVHVVPHQWUHTXLUHPHQWVIRUWKLVVWXG\
$Q\ DEQRUPDO ODERUDWRU\ WHVW UHVXOWV KHPDWRORJ\ FOLQLFDO FKHPLVWU\ RU XULQDO\VLV RU
RWKHU VDIHW\ DVVHVVPHQWV HJ (&*V UDGLRORJLFDO VFDQV YLWDO VLJQV PHDVXUHPHQWV
UHFRUGHGGXULQJDURXWLQHFOLQLFYLVLWLQFOXGLQJWKRVHWKDWZRUVHQIURPEDVHOLQHDQG
IHOWWREHFOLQLFDOO\VLJQLILFDQWLQWKHPHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKH,QYHVWLJDWRU
DUHWREHUHFRUGHGDVQRQVHULRXV$'5VRU6$(VDVDSSURSULDWH
6HFWLRQ± $QDO\VLV3RSXODWLRQ
2ULJLQDOWH[W
3RSXODWLRQVFRQVLGHUHGIRUDQDO\VLVDUHDVIROORZV
,QWHQWWRWUHDW,77VHW$OOUDQGRPL]HGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQHGRVHRI
WKHSUHVFULSWLRQRIVWXG\PHGLFDWLRQ HLWKHU))9,RUXVXDO,&6/$%$DVWKPD
PDLQWHQDQFHWKHUDS\7KH,77VHWZLOOEHXVHGWRDQDO\]HWKHSULPDU\HIILFDF\HQGSRLQW
DQDO\VLVWKHVHFRQGDU\HIILFDF\HQGSRLQWDQGRWKHUHIILFDF\HQGSRLQWV6XEMHFWVZLOOEH
DVVLJQHGWRWKHWUHDWPHQWJURXSDVUDQGRPL]HGIRUWKH,77VHW
3HUSURWRFRO33VHW DOO,77VXEMHFWVZLWKRXWDQ\PDMRUYLRODWLRQVRIVWXG\SURFHGXUHV
0DMRUSURWRFROYLRODWLRQVZLOOEHLGHQWLILHGSULRUWRGDWDEDVHORFN3URWRFROGHYLDWLRQV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
118
ZLOOEHUHYLHZHGDQGFODVVLILHGDVPLQRURUPDMRUGXULQJDGDWDUHYLHZPHHWLQJWKDWZLOO
EHKHOGEHIRUHGDWDEDVHORFN7KHH[FOXVLRQRIVXEMHFWVIURPWKH33VHWZLOOEHVSHFLILHG
DQGGRFXPHQWHGLQWKH5$3
6DIHW\VHW $OOHQUROOHGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQHGRVHRIWKHSUHVFULSWLRQRI
VWXG\PHGLFDWLRQHLWKHU))9,RUXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\DQG
FRQVLGHUHGDVWUHDWHG7KH6DIHW\VHWZLOOEHWKHEDVLVIRUVDIHW\DQDO\VHV6XEMHFWVZLOOEH
DVVLJQHGWRWKHWUHDWPHQWJURXSDVWUHDWHGIRUWKH6DIHW\VHW
5HYLVHGWH[W
3RSXODWLRQVFRQVLGHUHGIRUDQDO\VLVDUHDVIROORZV
,QWHQWWRWUHDW,77SRSXODWLRQ$OOUDQGRPL]HGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQH
GRVHRIWKHSUHVFULSWLRQRIVWXG\PHGLFDWLRQ HLWKHU))9,RUXVXDO,&6/$%$DVWKPD
PDLQWHQDQFHWKHUDS\7KH,77SRSXODWLRQ ZLOOEHXVHGWRDQDO\]HWKHSULPDU\HIILFDF\
HQGSRLQWDQDO\VLVWKHVHFRQGDU\HIILFDF\HQGSRLQWDQGRWKHUHIILFDF\HQGSRLQWV6XEMHFWV
ZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVUDQGRPL]HGIRUWKH,77SRSXODWLRQ
3HUSURWRFRO33SRSXODWLRQ DOO,77VXEMHFWVZLWKRXWDQ\PDMRUYLRODWLRQVRIVWXG\
SURFHGXUHV0DMRUSURWRFROYLRODWLRQVZLOOEHLGHQWLILHGSULRUWRGDWDEDVHORFN3URWRFRO
GHYLDWLRQVZLOOEHUHYLHZHGDQGFODVVLILHGDVPLQRURUPDMRUGXULQJDGDWDUHYLHZ
PHHWLQJWKDWZLOOEHKHOGEHIRUHGDWDEDVHORFN7KHH[FOXVLRQRIVXEMHFWVIURPWKH33
SRSXODWLRQ ZLOOEHVSHFLILHGDQGGRFXPHQWHGLQWKH5$3
6DIHW\SRSXODWLRQ $OOHQUROOHGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQHGRVHRIWKH
SUHVFULSWLRQRIVWXG\PHGLFDWLRQHLWKHU))9,RUXVXDO,&6/$%$DVWKPDPDLQWHQDQFH
WKHUDS\DQGFRQVLGHUHGDVWUHDWHG7KH6DIHW\SRSXODWLRQ ZLOOEHWKHEDVLVIRUVDIHW\
DQDO\VHV6XEMHFWVZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVWUHDWHGIRUWKH6DIHW\
SRSXODWLRQ
6HFWLRQ± .H\(OHPHQWVRI$QDO\VLV3ODQ
2ULJLQDOWH[W
7KHSULPDU\FRPSDULVRQRILQWHUHVWLVWKHFRPSDULVRQRIWKHFKDQJHIURPEDVHOLQH9LVLW
LQWKHWRWDO$&7VFRUHDVVHVVHGDW:HHN9LVLWEHWZHHQ))9,PFJPFJRU
PFJPFJ DQG XVXDO ,&6/$%$ LQKDODWLRQ SRZGHU IRU DVWKPD PDLQWHQDQFH
WKHUDS\
7KHSULPDU\VHWIRUDQDO\VLVLVWKHLQWHQWWRWUHDWVHW$VHQVLWLYLW\DQDO\VLVZLOOEH
SHUIRUPHGLQWKH33VHW
5HYLVHGWH[W
7KHSULPDU\FRPSDULVRQRILQWHUHVWLVWKHFRPSDULVRQRIWKHFKDQJHIURPEDVHOLQH9LVLW
LQWKHWRWDO$&7VFRUHDVVHVVHGDW:HHN9LVLWEHWZHHQ))9,PFJPFJRU

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
119
PFJPFJ DQG XVXDO ,&6/$%$ LQKDODWLRQ SRZGHU IRU DVWKPD PDLQWHQDQFH
WKHUDS\
7KHSULPDU\VHWIRUDQDO\VLVZLOOEHSHUIRUPHGRQ WKHLQWHQWWRWUHDWSRSXODWLRQ$
VHQVLWLYLW\DQDO\VLVZLOOEHSHUIRUPHGLQWKH33SRSXODWLRQ
6HFWLRQ± 3ULPDU\$QDO\VLV
2ULJLQDOWH[W
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7WRWDO
VFRUHDVVHVVHGDW:HHN9LVLW
7KHSULPDU\VHWRIDQDO\VLVLVWKH,77VHW
 1RQLQIHULRULW\WHVWLQJ
7KH QRQLQIHULRULW\ RI ))9, YHUVXV DQ\ RWKHU ,&6/$%$ '3, FRPSDUDWRU ZLOO EH
SULPDULO\WHVWHGLQDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFK7KHPRGHOZLOO
LQFOXGHIDFWRUVDQGFRYDULDWHVDVIROORZWUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN
DQG :HHN  EDVHOLQH $&7 WUHDWPHQW E\ YLVLW LQWHUDFWLRQ EDVHOLQH $&7 E\ YLVLW
LQWHUDFWLRQ JHQGHU DJH DQG SDWLHQW ZLOO EH ILWWHG DV D UDQGRP IDFWRU 7KH 5HVWULFWHG
0D[LPXP /LNHOLKRRG 5(0/ HVWLPDWLRQ DSSURDFK ZLOO EH XVHG DQG WKH GHIDXOW
FRYDULDQFH VWUXFWXUH ZLOO EH XQVWUXFWXUHG  &RQVLVWHQW ZLWK 0050 PRGHO ILWWLQJ QR
H[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUDJLYHQWLPHSRLQWZLOOEHSHUIRUPHG7KH
FRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRUZLOO
EHHVWLPDWHGDW:HHN9LVLWLQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHGLIWKH
QRQLQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQ
WKHGLIIHUHQFHEHWZHHQ))9,DQGDQ\RWKHUFRPSDUDWRUSRVLWLYHYDOXHVRIWKHGLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\DQDO\VHV
H +DQGOLQJPLVVLQJGDWD
:KLOHVXEMHFWVPLVVLQJ:HHN9LVLWGDWDEXWKDYLQJHDUOLHUGDWDZLOOEHLQFOXGHGLQ
WKH0050SULPDU\DQDO\VLVWKHLQWHUSUHWDELOLW\RIWKHUHVXOWVIURPWKHSULPDU\PRGHO
ZLOOGHSHQGRQWKHPLVVLQJGDWDVDWLVI\LQJWKH0LVVLQJDW5DQGRP0$57RVXSSRUW
WKHYDOLGLW\RIWKHFRQFOXVLRQVGUDZQIURPWKLVDQDO\VLVVHYHUDOVHQVLWLYLW\DQDO\VHVZLOO
EH SHUIRUPHG WR H[SORUH WKH GURSRXW SDWWHUQ DQG LWV SRVVLEOH LPSDFW RQ WUHDWPHQW
FRPSDULVRQV
 0LVVLQJ YDOXHV DW :HHN  9LVLW  ZLOO EH UHSODFHG E\ WKH SRVW
UDQGRPL]DWLRQODVWDYDLODEOHYDOXHHLWKHUWKHZHHNEDVHG$&7VFRUHRUWKH
$&7 VFRUH DW WUHDWPHQW ZLWKGUDZDO WLPH LI DQ\ LH EDVHG RQ WKH /DVW
2EVHUYDWLRQ&DUULHG)RUZDUGPHWKRG7KHFKDQJHIURPEDVHOLQHLQ$&7DW
:HHN  9LVLW  ZLOO EH DQDO\]HG LQ DQ $1&29$ PRGHO DGMXVWLQJ IRU
WUHDWPHQW DQG EDVHOLQH $&7 VFRUH 7KH WUHDWPHQW HIIHFW ))9, YHUVXV DQ\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
120
RWKHU,&6/$%$FRPSDUDWRUDQGLWVFRUUHVSRQGLQJFRQILGHQFHLQWHUYDO
ZLOOEHHVWLPDWHGLQWKLVPRGHOWRWHVWWKHQRQLQIHULRULW\K\SRWKHVLV
 0XOWLSOHLPSXWDWLRQ0,DQDO\VHVXWLOL]LQJFRYDULDWHVNQRZQWREHSUHGLFWLYH
RIUHVSRQVHVHDVRQDWUDQGRPL]DWLRQREVHUYHGYDOXHRI$&7DW:HHN
REVHUYHGYDOXHRI$&7DW:HHN9LVLW2WKHUFRYDULDWHVPD\EH
FRQVLGHUHGDQGLIVRLWZLOOEHGHWDLOHGLQWKH5$3
6WHS   )RU HDFK WUHDWPHQW JURXS VHSDUDWHO\ PLVVLQJ PHDVXUHPHQWV DUH
LPSXWHG IRU VXEMHFWV ZLWK D EDVHOLQH PHDVXUHPHQW ZKHUH WKHUH DUH PLVVLQJ
REVHUYDWLRQVDWHLWKHU:HHNRU:HHNXVLQJWKHDERYHFRYDULDWHVDQG
UHJUHVVLRQEDVHG LPSXWDWLRQ PHWKRG 7KH 0DUNRY &KDLQ 0RQWH &DUOR
0&0&PHWKRGIRU0,ZLOOEHXVHGDQGWHQVXFK VHWVRILPSXWHGGDWDZLOO
EHFUHDWHGHDFKZLWKWKHREVHUYHGYDOXHVRULPSXWHGYDOXHVIRUVXEMHFWVZLWK
PLVVLQJREVHUYDWLRQV
6WHS  (DFK LPSXWHG GDWD VHW ZLOO EH DQDO\]HG XVLQJ WKH SULPDU\ 0050
PRGHO7KHWUHDWPHQWHIIHFWIURPWKHVHDQDO\VHVZLOOWKHQEHSRROHGXVLQJ
VWDQGDUG0,WKHRU\WRPDNHDQRYHUDOOLQIHUHQFH7KHGLIIHUHQFHLQWKHOHDVW
VTXDUHV PHDQV EHWZHHQ WKH WZR JURXSV DW :HHN  9LVLW  DQG WKH
FRUUHVSRQGLQJFRQILGHQFHLQWHUYDOIRUWKHGLIIHUHQFHZLOOEHSUHVHQWHG
I
$ VHQVLWLYLW\ DQDO\VLV EDVHG RQ WKH VHPL SDUDPHWULF +RGJHV/HKPDQQ +/
DSSURDFKZLOOEHSURSRVHGWRDVVHVVWKHUREXVWQHVVRIWKH00500RGHOEDVHG
QRQLQIHULRULW\UHVXOWV7KH+/GLIIHUHQFHEHWZHHQJURXSVZLWKWKHFRUUHVSRQGLQJ
FRQILGHQFHLQWHUYDOZLOOEHSURYLGHG
J 6HQVLWLYLW\ DQDO\VHV IRU KDQGOLQJ WUHDWPHQW ZLWKGUDZDO ZKHQ WUHDWPHQW
ZLWKGUDZDORFFXUVDQDOWHUQDWLYHPHWKRGIRULPSXWLQJWKHPLVVLQJYDOXHDWWKH
QHDUHVWYLVLWDIWHUZLWKGUDZDOWLPHZLOOEHSURSRVHGWKHSULPDU\HQGSRLQWPLVVLQJ
YDOXHZLOOEHHVWLPDWHGE\WKHZRUVW$&7VFRUHREVHUYHGEHWZHHQEDVHOLQHYLVLW
LQFOXGHGDQGZLWKGUDZDOWLPHLQFOXGHG
K 7KH SULPDU\ DQDO\VLV LH EDVHG RQ WKH 0050 DSSURDFK DQG WKH VDPH
VHQVLWLYLW\DQDO\VHVSUHVHQWHGKHUHDERYHZLOOEHSHUIRUPHGLQWKH3HU3URWRFRO
VHW
5HYLVHGWH[W
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7WRWDO
VFRUHDVVHVVHGDW:HHN9LVLW
7KHSULPDU\SRSXODWLRQ RIDQDO\VLVZLOOEH WKH,77SRSXODWLRQ
 1RQLQIHULRULW\WHVWLQJ
7KH QRQLQIHULRULW\ RI ))9, YHUVXV DQ\ RWKHU ,&6/$%$ '3, FRPSDUDWRU ZLOO EH
SULPDULO\WHVWHGLQDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFK7KHPRGHOZLOO
LQFOXGHIDFWRUVDQGFRYDULDWHVDVIROORZWUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN
DQG :HHN  EDVHOLQH $&7 WUHDWPHQW E\ YLVLW LQWHUDFWLRQ EDVHOLQH $&7 E\ YLVLW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
121
LQWHUDFWLRQ JHQGHU DJH DQG SDWLHQW ZLOO EH ILWWHG DV D UDQGRP IDFWRU 7KH 5HVWULFWHG
0D[LPXP /LNHOLKRRG 5(0/ HVWLPDWLRQ DSSURDFK ZLOO EH XVHG DQG WKH GHIDXOW
FRYDULDQFH VWUXFWXUH ZLOO EH XQVWUXFWXUHG  &RQVLVWHQW ZLWK 0050 PRGHO ILWWLQJ QR
H[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUDJLYHQWLPHSRLQWZLOOEHSHUIRUPHG7KH
FRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRUZLOO
EHHVWLPDWHGDW:HHN9LVLWLQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHGLIWKH
QRQLQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQ
WKHGLIIHUHQFHEHWZHHQ))9,DQGDQ\RWKHUFRPSDUDWRUSRVLWLYHYDOXHVRIWKHGLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\DQDO\VHV
L
+DQGOLQJPLVVLQJGDWD
:KLOHVXEMHFWVPLVVLQJ:HHN9LVLWGDWDEXWKDYLQJHDUOLHUGDWDZLOOEHLQFOXGHGLQ
WKH0050SULPDU\DQDO\VLVWKHLQWHUSUHWDELOLW\RIWKHUHVXOWVIURPWKHSULPDU\PRGHO
ZLOOGHSHQGRQWKHPLVVLQJGDWDVDWLVI\LQJWKH0LVVLQJDW5DQGRP0$57RVXSSRUW
WKHYDOLGLW\RIWKHFRQFOXVLRQVGUDZQIURPWKLVDQDO\VLVVHYHUDOVHQVLWLYLW\DQDO\VHVZLOO
EH SHUIRUPHG WR H[SORUH WKH GURSRXW SDWWHUQ DQG LWV SRVVLEOH LPSDFW RQ WUHDWPHQW
FRPSDULVRQV
 0LVVLQJ YDOXHV DW :HHN  9LVLW  ZLOO EH UHSODFHG E\ WKH SRVW
UDQGRPL]DWLRQODVWDYDLODEOHYDOXHHLWKHUWKHZHHNEDVHG$&7VFRUHRUWKH
$&7 VFRUH DW WUHDWPHQW ZLWKGUDZDO WLPH LI DQ\ LH EDVHG RQ WKH /DVW
2EVHUYDWLRQ&DUULHG)RUZDUGPHWKRG7KHFKDQJHIURPEDVHOLQHLQ$&7DW
:HHN  9LVLW  ZLOO EH DQDO\]HG LQ DQ $1&29$ PRGHO DGMXVWLQJ IRU
WUHDWPHQW DQG EDVHOLQH $&7 VFRUH 7KH WUHDWPHQW HIIHFW ))9, YHUVXV DQ\
RWKHU,&6/$%$FRPSDUDWRUDQGLWVFRUUHVSRQGLQJFRQILGHQFHLQWHUYDO
ZLOOEHHVWLPDWHGLQWKLVPRGHOWRWHVWWKHQRQLQIHULRULW\K\SRWKHVLV
 0XOWLSOHLPSXWDWLRQ0,DQDO\VHVXWLOL]LQJFRYDULDWHVNQRZQWREHSUHGLFWLYH
RIUHVSRQVHVHDVRQDWUDQGRPL]DWLRQREVHUYHGYDOXHRI$&7DW:HHN
REVHUYHGYDOXHRI$&7DW:HHN9LVLW2WKHUFRYDULDWHVPD\EH
FRQVLGHUHGDQGLIVRLWZLOOEHGHWDLOHGLQWKH5$3
6WHS   )RU HDFK WUHDWPHQW JURXS VHSDUDWHO\ PLVVLQJ PHDVXUHPHQWV DUH
LPSXWHG IRU VXEMHFWV ZLWK D EDVHOLQH PHDVXUHPHQW ZKHUH WKHUH DUH PLVVLQJ
REVHUYDWLRQVDWHLWKHU:HHNRU:HHNXVLQJWKHDERYHFRYDULDWHVDQG
UHJUHVVLRQEDVHG LPSXWDWLRQ PHWKRG 7KH 0DUNRY &KDLQ 0RQWH &DUOR
0&0&PHWKRGIRU0,ZLOOEHXVHGDQGWHQVXFKVHWVRILPSXWHGGDWDZLOO
EHFUHDWHGHDFKZLWKWKHREVHUYHGYDOXHVRULPSXWHGYDOXHVIRUVXEMHFWVZLWK
PLVVLQJREVHUYDWLRQV
6WHS  (DFK LPSXWHG GDWD VHW ZLOO EH DQDO\]HG XVLQJ WKH SULPDU\ 0050
PRGHO7KHWUHDWPHQWHIIHFWIURPWKHVHDQDO\VHVZLOOWKHQEHSRROHGXVLQJ
VWDQGDUG0,WKHRU\WRPDNHDQRYHUDOOLQIHUHQFH7KHGLIIHUHQFHLQWKHOHDVW
VTXDUHV PHDQV EHWZHHQ WKH WZR JURXSV DW :HHN  9LVLW  DQG WKH
FRUUHVSRQGLQJFRQILGHQFHLQWHUYDOIRUWKHGLIIHUHQFHZLOOEHSUHVHQWHG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
122
M
$ VHQVLWLYLW\ DQDO\VLV EDVHG RQ WKH VHPL SDUDPHWULF +RGJHV/HKPDQQ +/
DSSURDFKZLOOEHSURSRVHGWRDVVHVVWKHUREXVWQHVVRIWKH00500RGHOEDVHG
QRQLQIHULRULW\UHVXOWV7KH+/GLIIHUHQFHEHWZHHQJURXSVZLWKWKHFRUUHVSRQGLQJ
FRQILGHQFHLQWHUYDOZLOOEHSURYLGHG
N 6HQVLWLYLW\ DQDO\VHV IRU KDQGOLQJ WUHDWPHQW ZLWKGUDZDO ZKHQ WUHDWPHQW
ZLWKGUDZDORFFXUVDQDOWHUQDWLYHPHWKRGIRULPSXWLQJWKHPLVVLQJYDOXHDWWKH
QHDUHVWYLVLWDIWHUZLWKGUDZDOWLPHZLOOEHSURSRVHGWKHSULPDU\HQGSRLQWPLVVLQJ
YDOXHZLOOEHHVWLPDWHGE\WKHZRUVW$&7VFRUHREVHUYHGEHWZHHQEDVHOLQHYLVLW
LQFOXGHGDQGZLWKGUDZDOWLPHLQFOXGHG
O
7KH SULPDU\ DQDO\VLV LH EDVHG RQ WKH 0050 DSSURDFK DQG WKH VDPH
VHQVLWLYLW\DQDO\VHVSUHVHQWHGKHUHDERYHZLOOEHSHUIRUPHGRQWKH3HU3URWRFRO
SRSXODWLRQ
6HFWLRQ± 6HFRQGDU\$QDO\VHV2WKHU6HFRQGDU\$QDO\VHV
2ULJLQDOWH[W
3URSHUXVHRIWKHPHGLFDOGHYLFH
7KHRWKHUNH\VHFRQGDU\HQGSRLQWZLOOEHWKHFRUUHFWXVHRIWKHLQKDOHUGHYLFHDVVHVVHGDW
UDQGRPLVDWLRQ9LVLWDW:HHN9LVLWDQGDW:HHN9LVLW7KHGHYLFHZLOO
EHFRQVLGHUHGDVDGHTXDWHO\XVHGLIWKHSDWLHQWGLGQ¶WPDNHDQ\7\SH$HUURUDOOFULWLFDO
LWHPVFRUUHFWDWWKHFRUUHVSRQGLQJYLVLWVUDQGRPLVDWLRQ>9LVLW@ZHHN>9LVLW@DQG
ZHHN>9LVLW@3URSRUWLRQVRIVXEMHFWVFRUUHFWO\XVLQJWKHGHYLFHZLOOEHHVWLPDWHG
ZLWKLQ HDFK JURXS $ FRUUHVSRQGLQJ  FRQILGHQFH LQWHUYDO RI WKH GLIIHUHQFH LQ
SURSRUWLRQVZLOODOVREHSURYLGHG$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHG
DQGZLOOEHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGQRFDXVDODVVRFLDWLRQ
ZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV
5HYLVHGWH[W
3URSHUXVHRIWKHPHGLFDOGHYLFH
7KHRWKHUNH\ VHFRQGDU\HQGSRLQWZLOOEHWKHFRUUHFWXVHRIWKHLQKDOHUGHYLFHDVVHVVHGDW
UDQGRPLVDWLRQ9LVLWDW:HHN9LVLWDQGDW:HHN9LVLW7KHGHYLFHZLOO
EH FRQVLGHUHG DV DGHTXDWHO\ XVHG LI WKH SDWLHQW GLGQ¶W PDNH DQ\ FULWLFDO HUURU DW WKH
FRUUHVSRQGLQJYLVLWVUDQGRPLVDWLRQ>9LVLW@ZHHN>9LVLW@DQGZHHN>9LVLW@
3URSRUWLRQVRIVXEMHFWVFRUUHFWO\XVLQJWKHGHYLFHZLOOEHHVWLPDWHGZLWKLQHDFKJURXS$
FRUUHVSRQGLQJ  FRQILGHQFH LQWHUYDO RI WKH GLIIHUHQFH LQ SURSRUWLRQV ZLOO DOVR EH
SURYLGHG$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOOEHGHWDLOHGLQWKH
5$3(YHQLIWHVWVZLOOEHSHUIRUPHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVH
DQDO\VHV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
123
6HFWLRQ± 2WKHU$QDO\VHV&KDQJHIURPEDVHOLQHLQSUHGRVH
WURXJK)(9
2ULJLQDOWH[W
7KHDQDO\VLVRIWKHRWKHUHQGSRLQWVGHILQHGLQWKLVVHFWLRQZLOOEHSURYLGHGIRU
H[SORUDWRU\SXUSRVHVRQO\$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOO
EHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGDQGFRQILGHQFHLQWHUYDOVZLOO
EHSURYLGHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV
&KDQJHIURPEDVHOLQHLQSUHGRVHWURXJK)(9
5HVXOWVZLOOEHVXPPDUL]HGIRUHDFKJURXSDQGWKHUHVXOWVRIWKHGLIIHUHQFHEHWZHHQ
JURXSVZLOOEHSUHVHQWHG ZLWKWKHFRUUHVSRQGLQJFRQILGHQFHLQWHUYDODW:HHN
9LVLW
5HVSRQVHWRWUHDWPHQW
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW25DSRLQW
LQFUHDVHIURPEDVHOLQHLQ$&7FKDQJH
7KHUHVSRQGHUDQDO\VHVZLOOEHFRQGXFWHGXVLQJDORJLVWLFUHJUHVVLRQPRGHODWDJLYHQ
9LVLWRU3KRQH&DOODGMXVWLQJIRUWUHDWPHQWDQGVWUDWLILFDWLRQIDFWRUVEDVHOLQH$&7VFRUH
FDWHJRUL]HG LQWR WZR FODVVHV EDVHOLQH DVWKPD WKHUDS\ DQG SRWHQWLDOO\ VHDVRQ DW
UDQGRPL]DWLRQ 7UHDWPHQW E\ VWUDWLILFDWLRQ IDFWRUV LQWHUDFWLRQ HIIHFWV ZLOO EH IXUWKHU
LQYHVWLJDWHGLQDGGLWLRQDOORJLVWLFPRGHOVDGMXVWLQJIRUWKHVHVSHFLILFHIIHFWV
5HYLVHGWH[W
7KHDQDO\VLVRIWKHRWKHUHQGSRLQWVGHILQHGLQWKLVVHFWLRQZLOOEHSURYLGHGIRU
H[SORUDWRU\SXUSRVHVRQO\$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOO
EHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGDQGFRQILGHQFHLQWHUYDOVZLOO
EHSURYLGHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV
&KDQJHIURPEDVHOLQHLQSUHGRVHWURXJK)(9
5HVXOWVZLOOEHVXPPDUL]HGIRUHDFKJURXSDW:HHN9LVLW0RUHGHWDLOZLOOEH
SURYLGHGLQWKH5$3
5HVSRQVHWRWUHDWPHQW
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW25DSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7FKDQJH
7KHUHVSRQGHUDQDO\VHVZLOOEHFRQGXFWHGXVLQJDORJLVWLFUHJUHVVLRQPRGHODWDJLYHQ
9LVLWRU3KRQH&DOODGMXVWLQJIRUWUHDWPHQWDQGVWUDWLILFDWLRQIDFWRUVEDVHOLQH$&7VFRUH
FDWHJRUL]HG LQWR WZR FODVVHV EDVHOLQH DVWKPD WKHUDS\ DQG SRWHQWLDOO\ VHDVRQ DW
UDQGRPL]DWLRQ 7UHDWPHQW E\ VWUDWLILFDWLRQ IDFWRUV LQWHUDFWLRQ HIIHFWV ZLOO EH IXUWKHU
LQYHVWLJDWHGLQDGGLWLRQDOORJLVWLFPRGHOVDGMXVWLQJ IRUWKHVHVSHFLILFHIIHFWV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
124
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW
7KHIUHTXHQF\DQGWKHSHUFHQWDJHRIVXEMHFWVZLWK$&7VFRUHDWDJLYHQYLVLW
ZLOOEHGHVFULEHGE\WUHDWPHQWJURXS0RUHGHWDLOZLOOEHSURYLGHGLQWKH5$3
!
&KDQJHIURPEDVHOLQHLQLQGLYLGXDOTXHVWLRQVFRUHVIRU$&7DWDJLYHQYLVLW
)RUHDFKTXHVWLRQWKHVWDWLVWLFDOSDUDPHWHUVRIWKHFKDQJHVZLOOEHVXPPDUL]HGE\
WUHDWPHQWJURXS0RUHGHWDLOZLOOEHSURYLGHGLQWKH5$3

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
125
3URWRFRO&KDQJHVIRU$PHQGPHQW$35IURP$PHQGPHQW
$8*
7KLVDPHQGPHQWKDVEHHQZULWWHQWRDOORZWKHDGGLWLRQRIDQHZFRXQWU\FRXQWULHV WRWKH
VWXG\DQGWRFODULI\WH[WWRPDNHWKHLQWHQWLRQRIWKHSURWRFROPRUHFOHDU&KDQJHVDUHWR
WH[WDUHOLVWHGLQWKLVDSSHQGL[
,QDGGLWLRQPLQRUDGPLQLVWUDWLYHXSGDWHVKDYHEHHQPDGH7KHVHZLOOQRWEHOLVWHGEHORZ
EXWLQFOXGH
!
5HIHUHQFHWR6WXG\5HIHUHQFH0DQXDO650LQSODFHRI6WXG\3URFHGXUHV
0DQXDO630
!
$GGLQJWUDGHPDUN70ZKHUHDSSOLFDEOH
!
$PHQGLQJWH[WWRPDNHODQJXDJHPRUHJHQHULFWRFRYHUSDUWLFLSDWLRQRXWVLGHRI
)UDQFH
!
2WKHUPLQRUFRUUHFWLRQVWRWH[W
:KHUHWKH$PHQGPHQW$SSOLHV
$PHQGPHQWLVDSSOLFDEOHWRDOOLQYHVWLJDWRUVLWHV
0HWKRGRI$PHQGPHQW
2ULJLQDODQGUHYLVHGWH[WVDUHVSHFLILHGDVIROORZV
2ULJLQDOWH[WDVZULWWHQLQWKHRULJLQDOSURWRFRO
5HYLVHGWH[WDVZULWWHQLQ$PHQGPHQW1RZLWKUHYLVLRQVLQVWULNHWKURXJK GHOHWHG
WH[WDQGEROGIRQW RUEROGXQGHUOLQH DGGLWLRQDOWH[W
7LWOH3DJHDQG6SRQVRU6LJQDWRU\3DJH
8SGDWHGWRUHIOHFWFXUUHQWDXWKRUVDQGVLJQDWRU\
6HFWLRQ3URWRFRO6\QRSVLVIRU6WXG\+=$
2ULJLQDO7H[W
2EMHFWLYHV(QGSRLQWV
Objectives
Endpoints
Secondary
!
7RDVVHVV(//,37$LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXV DQG
!
3HUFHQWDJHRIVXEMHFWVPDNLQJDWOHDVW
FULWLFDOHUURUDQGQRQFULWLFDOHUURUDW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
126
Objectives
Endpoints
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
:HHN9LVLWDQGDW:HHN9LVLW
LQGHSHQGHQWO\RIWKHXVHDW:HHN
9LVLW
Other
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQDW:HHN9LVLWDQG:HHN
9LVLW
!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN
9LVLWDQG:HHN9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
7H[WFKDQJHGWR
2EMHFWLYHV(QGSRLQWV
Objectives
Endpoints
Secondary
!
7RDVVHVV(//,37$ LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXVDQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVZLWKFRUUHFWXVH
RIGHYLFHGHILQHGDVQRWPDNLQJDQ\
FULWLFDOHUURURUQRQFULWLFDOHUURU
PDNLQJDWOHDVWFULWLFDOHUURUDQGQRQ
FULWLFDOHUURU DW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
Other
7RDVVHVVWKHDGKHUHQFH FRPSOLDQFHZLWK
VWXG\PHGLFDWLRQDQGVHOIUHSRUWHG
DGKHUHQFHWRVWXG\PHGLFDWLRQ DW:HHN
9LVLWDQG:HHN9LVLW
!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN
9LVLWDQG:HHN9LVLW
!
&RPSOLDQFH ZLWK VWXG\ PHGLFDWLRQ
IURPUDQGRPLVDWLRQ'D\WR:HHN
9LVLWIURP:HHN9LVLWWR
:HHN

9LVLW

DQG
IURP
UDQGRPLVDWLRQ 'D\  WR :HHN 
9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ $GKHUHQFH 5HSRUW 6FDOH
IRU $VWKPD DW WKH UDQGRPLVDWLRQ
'D\:HHN9LVLWDQG:HHN
9LVLW

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
127
5DWLRQDOHIRU&KDQJH
&RUUHFWLRQWRWKHGHILQLWLRQRI,QKDOHU&RUUHFW8VHDQGUHSODFHPHQWRI$GKHUHQFHZLWK
&RPSOLDQFHLQOLQHZLWKWKHGDWDEHLQJFROOHFWHGDQGWKHDQDO\VHVSODQQHG
6HFWLRQ3URWRFRO6\QRSVLVIRU6WXG\+=$
2ULJLQDOWH[W
7\SHDQG 1XPEHURI6XEMHFWV
$VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\RQO\LIHLWKHUDIILOLDWHGWRRUD
EHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURI UDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDVFUHHQIDLOXUHUDWHDSSUR[LPDWHO\VXEMHFWVZLOOKDYHWREHVFUHHQHG
LQWKHVWXG\LZWKVXEMHFWVFHQWHU
7H[WFKDQJHGWR
)UDQFH2QO\ $VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\RQO\LIHLWKHUDIILOLDWHG
WRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\  VWXG\FHQWHUVLQ)UDQFH ZLOOEHUHTXLUHGWRKDYH
DWRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDVFUHHQIDLOXUHUDWHDSSUR[LPDWHO\VXEMHFWVZLOOKDYHWREHVFUHHQHG
LQWKHVWXG\ZLWKVXEMHFWVFHQWHU
5DWLRQDOHIRU&KDQJH
8SGDWHGWRUHIOHFWWKHDGGLWLRQRIDQRWKHUFRXQWU\FRXQWULHV WRWKHVWXG\
6HFWLRQ6WXG\5DWLRQDOH
2ULJLQDOWH[W
,QKDOHGFRUWLFRVWHURLGV,&6DUHFRQVLGHUHGWKHPRVWHIIHFWLYHDQWLLQIODPPDWRU\
WUHDWPHQWVIRUDOOVHYHULWLHVRISHUVLVWHQWDVWKPD7KLVRSHQODEHOUDQGRPLVHGFOLQLFDO
VWXG\ZLOOHYDOXDWHWKHHIILFDF\DQGVDIHW\RI IOXWLFDVRQHIXURDWH))YLODQWHURO9,
,QKDODWLRQ3RZGHUFRPSDUHGZLWKH[LVWLQJIL[HGFRPELQDWLRQV,&6/$%$,QKDOHG
&RUWLFRVWHURLGV/RQJ$FWLQJ%HWD$JRQLVWVLQKDODWLRQSRZGHUV
7H[WFKDQJHGWR
,QKDOHGFRUWLFRVWHURLGV,&6DUHFRQVLGHUHGWKHPRVWHIIHFWLYHDQWLLQIODPPDWRU\
WUHDWPHQWVIRUDOOVHYHULWLHVRISHUVLVWHQWDVWKPD7KLVRSHQODEHOUDQGRPLVHGFOLQLFDO
VWXG\ZLOOHYDOXDWHWKHHIILFDF\DQGVDIHW\RIIOXWLFDVRQHIXURDWH))YLODQWHURO9,
,QKDODWLRQ3RZGHUFRPSDUHGZLWKQRPLQDWHG H[LVWLQJIL[HGFRPELQDWLRQV,&6/$%$
,QKDOHG&RUWLFRVWHURLGV/RQJ$FWLQJ%HWD$JRQLVWVLQKDODWLRQSRZGHUV

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
128
5DWLRQDOHIRU&KDQJH
8SGDWHGWRUHFRJQLVHWKHIDFWWKDWRWKHUFRXQWULHVKDYH RWKHU,&6/$%$FRPELQDWLRQV
EXWRQO\QRPLQDWHGFRPELQDWLRQVZLOOEHSHUPLWWHGLQWKHVWXG\WRUHIOHFWWKRVHDYDLODEOH
LQ)UDQFH
6HFWLRQ2EMHFWLYHVDQG(QGSRLQWV
2ULJLQDO7H[W
2EMHFWLYHV(QGSRLQWV
Objectives
Endpoints
Secondary
!
7RDVVHVV(//,37$LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXV DQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVPDNLQJDWOHDVW
FULWLFDOHUURUDQGQRQFULWLFDOHUURUDW
:HHN9LVLWDQGDW:HHN9LVLW
LQGHSHQGHQWO\RIWKHXVHDW:HHN
9LVLW
Other
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQDW:HHN9LVLWDQG:HHN
9LVLW
!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN
9LVLWDQG:HHN9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
7H[WFKDQJHGWR
2EMHFWLYHV(QGSRLQWV
Objectives
Endpoints
Secondary
!
7RDVVHVV(//,37$ LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXVDQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVZLWKFRUUHFWXVH
RIGHYLFHGHILQHGDVQRWPDNLQJDQ\
FULWLFDOHUURURUQRQFULWLFDOHUURU
PDNLQJDWOHDVWFULWLFDOHUURUDQGQRQ
FULWLFDOHUURU DW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
Other
7RDVVHVVWKHDGKHUHQFH FRPSOLDQFHZLWK
VWXG\PHGLFDWLRQDQGVHOIUHSRUWHG
!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
129
Objectives
Endpoints
DGKHUHQFHWRVWXG\PHGLFDWLRQ DW:HHN
9LVLWDQG:HHN9LVLW
9LVLWDQG:HHN9LVLW
!
&RPSOLDQFH ZLWK VWXG\ PHGLFDWLRQ
IURPUDQGRPLVDWLRQ'D\WR:HHN
9LVLWIURP:HHN9LVLWWR
:HHN

9LVLW

DQG
IURP
UDQGRPLVDWLRQ 'D\  WR :HHN 
9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ $GKHUHQFH 5HSRUW 6FDOH
IRU $VWKPD DW WKH UDQGRPLVDWLRQ
'D\:HHN9LVLWDQG:HHN
9LVLW
5DWLRQDOHIRU&KDQJH
&RUUHFWLRQWRWKHGHILQLWLRQRIµ&RUUHFW8VH¶DQGUHSODFHPHQWRI$GKHUHQFHZLWK
&RPSOLDQFHLQOLQHZLWKWKHGDWDEHLQJFROOHFWHGDQGWKHDQDO\VHVSODQQHG
6HFWLRQ2YHUDOO'HVLJQ
$GGHG7H[W
1RWH7RPDLQWDLQFRQVLVWHQF\DFURVVFRXQWULHVWKHFKRLFHRIXVXDOLQKDOHGGU\
SRZGHU,&6/$%$IL[HGFRPELQDWLRQZLOOEHOLPLWHGWR6HUHWLGH9LDQL'LVNXV)36
PFJPFJRUPFJPFJRU6\PELFRUW7XUERKDOHU %8')PFJPFJ
RUPFJPFJ6RPH FRXQWULHVKDYH RWKHU,&6/$%$IL[HGFRPELQDWLRQVDQG
RWKHUJHQHULFYHUVLRQVRI)36DQG%8')DYDLODEOHIRUWKHWUHDWPHQWRISDWLHQWV
ZLWKDVWKPDEXWWKHVHZLOOQRWEHSHUPLWWHGLQWKLVVWXG\$GGLWLRQDOO\VRPH
FRXQWULHVKDYH RSWLRQVIRUDORZHUGRVHRI9LDQL'LVNXV)36PFJPFJDQG
6\PELFRUW7XUERKDOHU %8')PFJPFJEXWWKHVHZLOOQRWEHSHUPLWWHGLQWKLV
VWXG\
5DWLRQDOHIRU&KDQJH
8SGDWHGWRUHFRJQLVHWKHIDFWWKDWRWKHUFRXQWULHVKDYH RWKHU,&6/$%$FRPELQDWLRQV
EXWRQO\QRPLQDWHGFRPELQDWLRQVZLOOEHSHUPLWWHGLQWKHVWXG\WRUHIOHFWWKRVHDYDLODEOH
LQ)UDQFH
6HFWLRQ2YHUDOO'HVLJQ
$GGHG7H[W
3DWLHQWVZKRIDLOVFUHHQLQJPD\EHUHVFUHHQHGRQO\XSRQDSSURYDOE\WKHPHGLFDO
PRQLWRU

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
130
5DWLRQDOHIRU&KDQJH
7RIRUPDOLVHWKHRSWLRQWRUHVFUHHQSDWLHQWVDVSHU6WXG\5HIHUHQFH0DQXDO
6HFWLRQ7\SHDQG1XPEHURI6XEMHFWV
2ULJLQDOWH[W
$VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\RQO\LIHLWKHUDIILOLDWHGWRRUD
EHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDVFUHHQIDLOXUHUDWHDSSUR[LPDWHO\VXEMHFWVZLOOKDYHWREHVFUHHQHG
LQWKHVWXG\ZLWKVXEMHFWVFHQWHU
7H[WFKDQJHG WR
)UDQFHRQO\$VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\RQO\LIHLWKHUDIILOLDWHG
WRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\  VWXG\FHQWHUVLQ)UDQFH ZLOOEHUHTXLUHGWRKDYH
DWRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDVFUHHQIDLOXUHUDWHDSSUR[LPDWHO\VXEMHFWVZLOOKDYHWREHVFUHHQHG
LQWKHVWXG\ ZLWKVXEMHFWVFHQWHU
5DWLRQDOHIRU&KDQJH
8SGDWHGWRUHIOHFWWKHDGGLWLRQRI DQRWKHUFRXQWU\FRXQWULHV WRWKHVWXG\
6HFWLRQ([FOXVLRQ&ULWHULD
2ULJLQDOWH[W
6XEMHFWVKDYLQJDVHYHUHDQGXQVWDEOHDVWKPD ZLWK$&7 VFRUHDW9LVLWDQG
DW9LVLWKLVWRU\RIUHSHDWHGVHYHUHH[DFHUEDWLRQV\HDUDQGRUDVHYHUHH[DFHUEDWLRQ
LQWKHSUHYLRXVZHHNVEHIRUH9LVLWDQG9LVLW
7H[WFKDQJHGWR
 6XEMHFWVKDYLQJDVHYHUHDQGXQVWDEOHDVWKPD ZLWK$&7 VFRUHDW9LVLWDQG
DW 9LVLW  DQGRU D KLVWRU\ RI UHSHDWHG VHYHUH H[DFHUEDWLRQV \HDU DQGRU D VHYHUH
H[DFHUEDWLRQLQWKHSUHYLRXVZHHNVEHIRUH9LVLWDQG9LVLW
5DWLRQDOHIRU&KDQJH
7RFODULI\WKHLQWHQWRIWKLVH[FOXVLRQFULWHULD

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
131
6HFWLRQ([FOXVLRQ&ULWHULD
2ULJLQDOWH[W
 6XEMHFWV WUHDWHG E\ WKH PRQRFORQDO DQWLERG\ RPDOL]XPDE ;RODLU DW 9LVLW 
7UHDWPHQWZLWK;RODLULVQRWDOORZHGGXULQJWKHVWXG\
7H[WFKDQJHGWR
 6XEMHFWV WUHDWHG E\ WKH PRQRFORQDO DQWLERG\ RPDOL]XPDE ;RODLU RU
PHSROL]XPDE1XFDOD DW9LVLW7UHDWPHQWZLWK;RODLURU1XFDOD LVQRWDOORZHG
GXULQJWKHVWXG\
5DWLRQDOHIRU&KDQJH
0HSROL]XPDE1XFDODLVDQHZOLFHQVHGWUHDWPHQWWKDWVKRXOGEHH[FOXGHG
6HFWLRQ6FUHHQLQJ%DVHOLQH)DLOXUHV
$GGHG7H[W
3DWLHQWVWKDWIDLOVFUHHQLQJPD\EHUHVFUHHQHGRQO\XSRQDSSURYDOE\WKHPHGLFDO
PRQLWRU
5DWLRQDOHIRU&KDQJH
7RIRUPDOLVHWKHRSWLRQWRUHVFUHHQSDWLHQWVDVSHU6WXG\5HIHUHQFH0DQXDO
6HFWLRQ,QYHVWLJDWLRQDO3URGXFWDQG2WKHU6WXG\7UHDWPHQW
2ULJLQDOWH[W
*OD[R6PLWK.OLQH&OLQLFDO7ULDOV6XSSOLHVZLOOSURYLGHWKHLQYHVWLJDWLRQDOSURGXFWV
))9,5HOYDU (OOLSWD DQGFRPSDUDWLYHWUHDWPHQWVLH6HUHWLGH 'LVNXV
6\PELFRUW 7XUEXKDOHUDVZHOODVUHVFXHPHGLFDWLRQ6DOEXWDPROIRUXVHLQWKLVVWXG\
1HZ,&6/$%$'3,RU'3,FRSLHVRIH[LVWLQJPDUNHWHG,&6/$%$LIDQ\LQ)UDQFHDW
WKHWLPHRIWKHVWXG\ZLOOQRWEHFRQVLGHUHGLQWKLVWULDO
(DFKVXEMHFWUDQGRPLVHGWRWKH))9,DUPZLOOEHLQVWUXFWHGWRDGPLQLVWHUWKHVWXG\
PHGLFDWLRQRQFHGDLO\E\UHDGLQJWKHOHDIOHWDQGGHPRQVWUDWLRQRILWXVHDWWKHVDPH
WLPHRIWKHGD\IRUWKHGXUDWLRQRIWKHWUHDWPHQWSHULRG(DFKVXEMHFWZLOOEHDGYLVHGWR
DGKHUHWR))9,GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\7KHLQYHVWLJDWRUPD\DGMXVWWKH
GRVHRI))9,DFFRUGLQJWRWKHVXEMHFWV¶UHVSRQVHVWDUWLQJZLWK))9,PFJPFJ
(DFKVXEMHFWLQLWLDWLQJRWKHU,&6/$%$PDLQWHQDQFHWKHUDS\ZLOOEHUHPLQGHGDERXWWKH
WHFKQLTXHVRIKRZWRXVHWKHLUPDLQWHQDQFHPHGLFDWLRQE\UHDGLQJWKHOHDIOHWDQG
GHPRQVWUDWLRQRILWXVHDQGWKHFRUUHFWGRVLQJ(DFKVXEMHFWZLOOEHDGYLVHGWRDGKHUHWR
,&6/$%$GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\VWDUWLQJE\)36PFJPFJRUE\

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
132
%8')PFJPFJDFFRUGLQJWRWKH,QYHVWLJDWRU¶VGHFLVLRQ7KH,QYHVWLJDWRUPD\
DGMXVWWKHGRVHRIHDFKSURGXFWDFFRUGLQJWRWKHVXEMHFWV¶UHVSRQVH
7H[WFKDQJHGWR
*OD[R6PLWK.OLQH&OLQLFDO7ULDOV6XSSOLHVZLOO SURYLGHWKHLQYHVWLJDWLRQDOSURGXFWV
))9,5HOYDU(OOLSWDDQGFRPSDUDWLYHWUHDWPHQWVLH6HUHWLGH'LVNXV6\PELFRUW
7XUEXKDOHU DVZHOODVU5HVFXHPHGLFDWLRQ6DOEXWDPROIRUXVHLQWKLVVWXG\ZLOOEH
SURYLGHGORFDOO\E\*6.LQHDFKFRXQWU\
1HZ,&6/$%$'3,RU'3,FRSLHVRIH[LVWLQJPDUNHWHG,&6/$%$LIDQ\LQ)UDQFH DW
WKHWLPHRIWKHVWXG\ZLOOQRWEHFRQVLGHUHGLQWKLVWULDO
(DFKVXEMHFWUDQGRPLVHGWRWKH))9,DUPZLOOEHLQVWUXFWHGWRDGPLQLVWHUWKHVWXG\
PHGLFDWLRQRQFHGDLO\E\UHDGLQJWKHOHDIOHWDQGGHPRQVWUDWLRQRILWXVHDWWKHVDPH
WLPHRIWKHGD\IRUWKHGXUDWLRQRIWKHWUHDWPHQWSHULRG(DFKVXEMHFWZLOOEHDGYLVHGWR
DGKHUHWR))9,GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\VWDUWLQJZLWK))9,
PFJPFJ7KHLQYHVWLJDWRURUDSSURSULDWHO\TXDOLILHGGHVLJQHHPD\DGMXVW
LQFUHDVH WKHGRVHRI))9,DFFRUGLQJWRWKHVXEMHFWV¶UHVSRQVH VWDUWLQJZLWK))9,
PFJPFJ
(DFKVXEMHFWLQLWLDWLQJRWKHU,&6/$%$PDLQWHQDQFHWKHUDS\ZLOOEHUHPLQGHGDERXWWKH
WHFKQLTXHVRIKRZWRXVHWKHLUPDLQWHQDQFHPHGLFDWLRQE\UHDGLQJWKHOHDIOHWDQG
GHPRQVWUDWLRQRILWXVHDQGWKHFRUUHFWGRVLQJ(DFKVXEMHFWZLOOEHDGYLVHGWRDGKHUHWR
,&6/$%$GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\VWDUWLQJE\ ZLWK)36PFJPFJ
RUE\ ZLWK%8')PFJPFJDFFRUGLQJWRWKH,QYHVWLJDWRU¶VGHFLVLRQ7KH
,QYHVWLJDWRUPD\DGMXVW LQFUHDVH WKHGRVHRIHDFKSURGXFWDFFRUGLQJWRWKHVXEMHFWV¶
UHVSRQVH
5DWLRQDOHIRU&KDQJH
7RFODULI\WKHVWDUWLQJGRVHDQGWKHRSWLRQRQO\WRLQFUHDVHWKHGRVHRIVWXG\PHGLFDWLRQ
6HFWLRQ7UHDWPHQW$VVLJQPHQW
2ULJLQDOWH[W
6XEMHFWVZLOOEHUDQGRPL]HGWRRQHRIWKHIROORZLQJWUHDWPHQWJURXSV
!
))9,DVSHUGRVHJXLGDQFHEHORZ
!
,QLWLDWHRQXVXDOLQKDOHGGU\SRZGHU,&6/$%$IL[HGFRPELQDWLRQIRUDVWKPD
PDLQWHQDQFHWKHUDS\LH6HUHWLGH'LVNXV RU6\PELFRUW 7XUEXKDOHU DFFRUGLQJWR
XVXDOSK\VLFLDQ¶VSUHVFULSWLRQ
7H[WFKDQJHGWR
6XEMHFWVZLOOEHUDQGRPL]HGWRRQHRIWKHIROORZLQJWUHDWPHQWJURXSV
!
))9,DVSHUGRVHJXLGDQFHEHORZ

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
133
!
,QLWLDWHRQXVXDO 8VXDO LQKDOHGGU\SRZGHU,&6/$%$IL[HGFRPELQDWLRQIRUDVWKPD
PDLQWHQDQFHWKHUDS\LH OLPLWHGWR6HUHWLGH9LDQL 'LVNXVRU6\PELFRUW 7XUEXKDOHU
DFFRUGLQJWRXVXDOSK\VLFLDQ¶VSUHVFULSWLRQ
1RWH7RPDLQWDLQFRQVLVWHQF\DFURVVFRXQWULHVWKHFKRLFHRIXVXDOLQKDOHGGU\
SRZGHU,&6/$%$IL[HGFRPELQDWLRQZLOOEHOLPLWHGWR6HUHWLGH9LDQL'LVNXV)36
PFJPFJRUPFJPFJRU6\PELFRUW7XUERKDOHU %8')PFJPFJ
RUPFJPFJ6RPH FRXQWULHVKDYHRWKHU,&6/$%$IL[HGFRPELQDWLRQVDQG
RWKHUJHQHULFYHUVLRQVRI)36DQG%8')DYDLODEOHIRUWKHWUHDWPHQWRISDWLHQWV
ZLWKDVWKPDEXWWKHVHZLOOQRWEHSHUPLWWHGLQWKLVVWXG\$GGLWLRQDOO\VRPH
FRXQWULHVKDYH RSWLRQVIRUDORZHUGRVHRI9LDQL'LVNXV)36PFJPFJDQG
6\PELFRUW7XUERKDOHU %8')PFJPFJEXWWKHVHZLOOQRW EHSHUPLWWHGLQWKLV
VWXG\
5DWLRQDOHIRU&KDQJH
8SGDWHGWRUHFRJQLVHWKHIDFWWKDWRWKHUFRXQWULHVKDYH RWKHU,&6/$%$FRPELQDWLRQV
EXWRQO\QRPLQDWHGFRPELQDWLRQVZLOOEHSHUPLWWHGLQWKHVWXG\WRUHIOHFWWKRVHDYDLODEOH
LQ)UDQFH
6HFWLRQ3ODQQHG 'RVH$GMXVWPHQWV
2ULJLQDOWH[W
6XEMHFWVUDQGRPLVHGWRWKHXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\DUPFDQKDYH
WKHLUWUHDWPHQWDGMXVWHGDVZRXOGEHQRUPDOFOLQLFDOSUDFWLFHDWWKH,QYHVWLJDWRU¶V
GLVFUHWLRQ7KLVZLOOQRWUHTXLUHWKHVXEMHFWWREHZLWKGUDZQIURPWKHVWXG\7KHVH
VXEMHFWVVKRXOGQRWUHFHLYH))9,LIWKHPHGLFDWLRQLVPDUNHWHGGXULQJWKHVWXG\SHULRG
6XEMHFWVUDQGRPL]HGWRWKH))9,DUPDQGIRUZKRPLWLVFRQVLGHUHGDSSURSULDWH
QHFHVVDU\WRDGMXVWWUHDWPHQWFDQKDYHWKHLUUHJLPHQFKDQJHGDVUHTXLUHGDVSHUQRUPDO
FOLQLFDOSUDFWLFHDWDQ\SRLQWLQWKHVWXG\DQGWKHVXEMHFWFRXOGUHPDLQLQWKHVWXG\
6XEMHFWVRQ))9,DUPFDQDOVRFKDQJHEHWZHHQWKHWZR))9,GRVHVDVDSSURSULDWHDQG
DWWKH,QYHVWLJDWRU¶VGLVFUHWLRQ
7H[WFKDQJHGWR
6XEMHFWVIRUZKRPLWLVFRQVLGHUHGDSSURSULDWHQHFHVVDU\WRDGMXVWWUHDWPHQW
UDQGRPLVHGWRWKHXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\DUP FDQKDYHWKHLU
WUHDWPHQWDGMXVWHG GRVHLQFUHDVHGIURPWKHVWDUWLQJGRVHDVZRXOGEHQRUPDOFOLQLFDO
SUDFWLFHDWWKH,QYHVWLJDWRU¶VGLVFUHWLRQ7KLVZLOOQRWUHTXLUHWKHVXEMHFWWREHZLWKGUDZQ
IURPWKHVWXG\7KHVHVXEMHFWVVKRXOGQRWUHFHLYH))9,LIWKHPHGLFDWLRQLVPDUNHWHG
GXULQJWKHVWXG\SHULRG
6XEMHFWVUDQGRPL]HGWRWKH))9,DUPDQGIRUZKRPLWLVFRQVLGHUHGDSSURSULDWH
QHFHVVDU\WRDGMXVWWUHDWPHQWFDQKDYHWKHLUUHJLPHQFKDQJHGDVUHTXLUHGDVSHUQRUPDO
FOLQLFDOSUDFWLFHDWDQ\SRLQWLQWKHVWXG\DQGWKHVXEMHFWFRXOGUHPDLQLQWKHVWXG\
6XEMHFWVRQ))9,DUPFDQDOVRFKDQJHEHWZHHQWKHWZR))9,GRVHVDVDSSURSULDWHDQG
DWWKH,QYHVWLJDWRU¶VGLVFUHWLRQ

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
134
,WLVQRWSHUPLWWHGIRUSDWLHQWVWREHVZLWFKHGWRDGLIIHUHQWWUHDWPHQWLHSDWLHQWV
UDQGRPLVHGWRWKHXVXDO,&6/$%$DUPFDQQRWFKDQJHWRDGLIIHUHQW,&6/$%$RU
UHFHLYH))9,3DWLHQWVUDQGRPLVHGWRWKH))9,DUPFDQQRWUHFHLYHXVXDO
,&6/$%$,IDVZLWFKEHWZHHQSURGXFWVLVUHTXLUHGWKHSDWLHQWVKRXOGEH
ZLWKGUDZQIURPWKHVWXG\
5DWLRQDOHIRU&KDQJH
7H[WDGMXVWHGWRFODULI\WKDWGRVHLQFUHDVHVDUHSHUPLWWHGEXWVZLWFKLQJWUHDWPHQWVLVQRW
6HFWLRQ &RPSOLDQFHZLWK6WXG\7UHDWPHQW$GPLQLVWUDWLRQ
2ULJLQDO7H[W
7UHDWPHQWDGKHUHQFHZLWKVWXG\PHGLFDWLRQZLOOEHDVVHVVHGEDVHGRQDQDO\VLVRI
PHGLFDWLRQVGLVSHQVHGDQGFROOHFWHGGXULQJWKHVWXG\DQGRQ0HGLFDWLRQ$GKHUHQFH
5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDWUDQGRPLVDWLRQ'D\DW:HHN
DQGDW:HHN
7H[WFKDQJHGWR
2YHUDOO7WUHDWPHQWDGKHUHQFH FRPSOLDQFHZLWKVWXG\PHGLFDWLRQZLOOEHDVVHVVHG
FDOFXODWHGIRUHDFKW\SHRILQKDOHUVHSDUDWHO\DV

7RWDOQXPEHURILQKDODWLRQVWDNHQLVWKH WRWDOQXPEHURIGRVHVWDNHQIURPDOO
LQKDOHUVGXULQJWKHWLPHSHULRGDVDVVHVVHGIURPGRVHFRXQWHUGDWDFROOHFWHGRQ
WKHH&5)

([SHFWHG,QKDODWLRQVLVWKHH[SHFWHGQXPEHURILQKDODWLRQVSHUGD\IRU
(OOLSWD70IRU'LVNXV70 DQGRUIRU7XUEXKDOHU70 GHSHQGLQJRQWKHGRVH

6WDUWGDWHDQG6WRSGDWHDUHWKHHDUOLHVWWUHDWPHQWVWDUWGDWHDQGWKHODWHVW
WUHDWPHQWVWRSGDWHUHVSHFWLYHO\IRUDOOLQKDOHUVXVHGLQWKHFDOFXODWLRQ
7UHDWPHQWFRPSOLDQFHZLOOEHDVVHVVHGIRUWKHSHULRGIURPUDQGRPLVDWLRQ'D\
XQWLO:HHN9LVLWIURP:HHN9LVLWXQWLO:HHN9LVLWDQGDOVR
RYHUDOOIURPUDQGRPLVDWLRQ'D\XQWLO:HHN9LVLW
6XEMHFW¶VVHOIUHSRUWHGDGKHUHQFHWRPHGLFDWLRQZLOOEHHYDOXDWHGEDVHGRQDQDO\VLV
RI DQGRQ 0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHV DW
UDQGRPLVDWLRQ'D\DW:HHNDQGDW:HHN
5DWLRQDOHIRU&KDQJH
5HSODFHPHQWRIWKHWHUP$GKHUHQFHZLWKWKHWHUP&RPSOLDQFHLQOLQHZLWKWKHGDWDEHLQJ
FROOHFWHGDQGWKHDQDO\VHVSODQQHG$GHVFULSWLRQRIKRZWKLVZLOOEHDVVHVVHGKDVEHHQ
DGGHG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
135
6HFWLRQ7UHDWPHQWDIWHUWKH(QGRIWKH6WXG\
2ULJLQDOWH[W
7KHLQYHVWLJDWRULVUHVSRQVLEOHIRUHQVXULQJWKDWFRQVLGHUDWLRQKDVEHHQJLYHQWRWKHSRVW
VWXG\FDUHRIWKHSDWLHQW¶VPHGLFDOFRQGLWLRQZKHWKHURUQRW*6.LVSURYLGLQJVSHFLILF
SRVWVWXG\WUHDWPHQW
7H[WFKDQJHGWR
7KHLQYHVWLJDWRULVUHVSRQVLEOHIRUHQVXULQJWKDWFRQVLGHUDWLRQKDVEHHQJLYHQWRWKHSRVW
VWXG\FDUHRIWKHSDWLHQW¶VPHGLFDOFRQGLWLRQ ZKHWKHURUQRW *6.LVSURYLGLQJVSHFLILF
ZLOOQRWSURYLGHSRVWVWXG\WUHDWPHQW
5DWLRQDOHIRU&KDQJH
&ODULILFDWLRQWKDW*6.ZLOOQRWSURYLGHSRVWVWXG\WUHDWPHQW
6HFWLRQ3URKLELWHG0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
2ULJLQDOWH[W
!
6\VWHPLFFRUWLFRVWHURLGVH[FHSWLQFDVHRIDVHYHUHDVWKPDH[DFHUEDWLRQ
!
0RQRFORQDODQWLERG\RPDOL]XPDE;RODLU
7H[WFKDQJHGWR
!
6\VWHPLFFRUWLFRVWHURLGVH[FHSWLQFDVHRIDVHYHUHDVWKPDH[DFHUEDWLRQ
!
0RQRFORQDODQWLERGLHVRPDOL]XPDE;RODLUDQGPHSROL]XPDE1XFDOD
5DWLRQDOHIRU&KDQJH
0HSROL]XPDE1XFDODLVDQHZOLFHQVHGWUHDWPHQWWKDWVKRXOGEHSURKLELWHG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
136
6HFWLRQ7LPHDQG(YHQWV7DEOH+HDGHUURZ	)RRWQRWH
2ULJLQDOWH[W
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone call 1
Visit 4**
Visit 5
Phone call 2
Visit 6
Early Withdrawal
7H[WFKDQJHGWR
Study Visits
Visit 1*
Screening#
Visit 2*
Randomisation
Visit 3
Phone call 1
Visit 4**
Visit 5
Phone call 2
Visit 6
Early Withdrawal
3DWLHQWVWKDWIDLOVFUHHQLQJPD\EHUHVFUHHQHGRQO\XSRQDSSURYDOE\WKHPHGLFDOPRQLWRU
5DWLRQDOHIRU&KDQJH
7RIRUPDOLVHWKHRSWLRQWRUHVFUHHQSDWLHQWVDVSHU6WXG\5HIHUHQFH0DQXDO



2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
137
6HFWLRQ7LPHDQG(YHQWV7DEOH5$0261*5RZDQG)RRWQRWH
2ULJLQDOWH[W
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone call 1
Visit 4**
Visit 5
Phone call 2
Visit 6
Early Withdrawal
Study week (± specified no. of days)
'D\WR
'D\
:HHN  
GD\V
:HHN
GD\V
:HHN  
GD\V
:HHN
GD\V
(DUO\:LWKGUDZDO
RAMOS/eCRF
5$0261*
x
x
7H[WFKDQJHGWR
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone call 1
Visit 4**
Visit 5
Phone call 2
Visit 6
Early Withdrawal
Study week (± specified no. of days)
'D\WR
'D\
:HHN  
GD\V
:HHN
GD\V
:HHN  
GD\V
:HHN
GD\V
(DUO\:LWKGUDZDO
RAMOS/eCRF
5$0261*
x
x
x
x
x
≠  France Only
5DWLRQDOHIRU&KDQJH
5$0261*DW6FUHHQLQJ9LVLWDQG(DUO\:LWKGUDZDOZDVPLVVHGIURPWKH7LPHDQG(YHQWV7DEOHLQHUURU



2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
138
6HFWLRQ0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD
0$56$
2ULJLQDO7H[W
5HSRUWHGDGKHUHQFHWRPHGLFDWLRQZLOOEHDVVHVVHGZLWKWKH0HGLFDWLRQ$GKHUHQFH
5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDW9LVLW:HHN9LVLWDQG
:HHN9LVLW(DUO\:LWKGUDZDOYLVLW
$PHQGHG7H[W
6XEMHFW¶VVHOIU5HSRUWHGDGKHUHQFHWR VWXG\ PHGLFDWLRQZLOOEHDVVHVVHGZLWKWKH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDW9LVLW
:HHN9LVLWDQG:HHN9LVLW(DUO\:LWKGUDZDOYLVLW
5DWLRQDOHIRUFKDQJH
7RHQVXUHFODULW\WKDWWKH0$56$TXHVWLRQQDLUHLVVHOIUHSRUWHGDGKHUHQFH
6HFWLRQ6HFRQGDU\$QDO\VHV
2ULJLQDO7H[W
2WKHUVHFRQGDU\DQDO\VHV
3URSHUXVHRIWKHPHGLFDOGHYLFH
7KHRWKHUNH\VHFRQGDU\HQGSRLQWZLOOEHWKHFRUUHFWXVHRIWKHLQKDOHUGHYLFHDVVHVVHGDW
UDQGRPLVDWLRQ9LVLWDW:HHN9LVLWDQGDW:HHN9LVLW7KHGHYLFHZLOO
EHFRQVLGHUHGDVDGHTXDWHO\XVHGLIWKHSDWLHQWGLGQ¶WPDNHDQ\FULWLFDOHUURUDWWKH
FRUUHVSRQGLQJYLVLWVUDQGRPLVDWLRQ>9LVLW@ZHHN>9LVLW@DQGZHHN>9LVLW@
3URSRUWLRQVRIVXEMHFWVFRUUHFWO\XVLQJWKHGHYLFHZLOOEHHVWLPDWHGZLWKLQHDFKJURXS$
FRUUHVSRQGLQJFRQILGHQFHLQWHUYDORIWKHGLIIHUHQFHLQSURSRUWLRQVZLOODOVREH
SURYLGHG$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOOEHGHWDLOHGLQWKH
5$3(YHQLIWHVWVZLOOEHSHUIRUPHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVH
DQDO\VHV
7H[WFKDQJHGWR
2WKHUVHFRQGDU\DQDO\VHV
3URSHUXVHRIWKHPHGLFDOGHYLFH
7KHRWKHUNH\VHFRQGDU\HQGSRLQWZLOOEHWKHFRUUHFWXVHRIWKHLQKDOHUGHYLFHDVVHVVHGDW
UDQGRPLVDWLRQ9LVLWDW :HHN9LVLWDQGDW:HHN9LVLW7KHGHYLFHZLOO
EHFRQVLGHUHGDVDGHTXDWHO\XVHGLIWKHSDWLHQWGLGQ¶WPDNHDQ\FULWLFDOHUURURUQRQ
FULWLFDOHUURUDWWKHFRUUHVSRQGLQJYLVLWVUDQGRPLVDWLRQ>9LVLW@ZHHN>9LVLW@DQG
ZHHN>9LVLW@3URSRUWLRQV 3HUFHQWDJHVRIVXEMHFWVFRUUHFWO\XVLQJWKHGHYLFHZLOOEH
HVWLPDWHG FDOFXODWHGZLWKLQHDFKJURXS$FRUUHVSRQGLQJFRQILGHQFHLQWHUYDORIWKH

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
139
GLIIHUHQFHLQSURSRUWLRQV SHUFHQWDJHVZLOODOVREHSURYLGHG)XUWKHUPRUHWKH
SHUFHQWDJHRIVXEMHFWVZLWKRYHUDOOHUURUDWOHDVWRQHFULWLFDOHUURUDQGDWOHDVWRQH
QRQFULWLFDOHUURUZLOOEHSUHVHQWHGE\WUHDWPHQWJURXSDORQJZLWKWKHSHUFHQWDJH
PDNLQJHDFKVSHFLILFHUURU $GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQG
ZLOOEHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGQRFDXVDODVVRFLDWLRQZLOOEH
LQIHUUHGIURPWKHVHDQDO\VHV
5DWLRQDOHIRU&KDQJH
&ODULILFDWLRQRIDQDO\VHVIRUµ,QKDOHU&RUUHFW8VH¶DVVHVVPHQW
6HFWLRQ2WKHU$QDO\VHV
2ULJLQDO7H[W
$GKHUHQFHZLWKVWXG\ PHGLFDWLRQ
!
1XPEHURISHUFHQWDJHRIPHGLFDWLRQVGLVSHQVHGDQGFROOHFWHGGXULQJWKHVWXG\ZLOO
EHWDEXODWHGIRUHDFKYLVLWDQGE\WUHDWPHQWJURXS
!
7KHVFRUHIRU0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$DW'D\
:HHNDQG:HHNZLOOEHGHVFULEHGE\WUHDWPHQWJURXS
7H[WFKDQJHGWR
$GKHUHQFH &RPSOLDQFHZLWKVWXG\PHGLFDWLRQDQGVHOIUHSRUWHGDGKHUHQFHWRVWXG\
PHGLFDWLRQ
!
1XPEHURISHUFHQWDJHRIPHGLFDWLRQVGLVSHQVHGDQGFROOHFWHGGXULQJWKHVWXG\ZLOO
EHWDEXODWHGIRUHDFKYLVLWDQGE\WUHDWPHQWJURXS
!
2YHUDOOWUHDWPHQWFRPSOLDQFHZLWKVWXG\PHGLFDWLRQIURPUDQGRPLVDWLRQ'D\
WR:HHN9LVLWIURP:HHN9LVLWWR:HHN9LVLWDQGIURP
UDQGRPLVDWLRQ 'D\  WR :HHN  9LVLW  ZLOO EH GHVFULEHG E\ WUHDWPHQW
JURXS
!
7KHVFRUHIRU0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$DW'D\
:HHNDQG:HHNZLOOEHGHVFULEHGE\WUHDWPHQWJURXS
5DWLRQDOHIRUFKDQJH
5HSODFHPHQWRIWKHWHUP$GKHUHQFHZLWKWKHWHUP&RPSOLDQFHLQOLQHZLWKWKHGDWDEHLQJ
FROOHFWHGDQGWKHDQDO\VHVSODQQHG

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
140
6HFWLRQ$QDO\VLV3RSXODWLRQV
2ULJLQDOWH[W
3HUSURWRFRO33SRSXODWLRQ DOO,77VXEMHFWVZLWKRXWDQ\PDMRUYLRODWLRQVRIVWXG\
SURFHGXUHV0DMRUSURWRFROYLRODWLRQVZLOOEHLGHQWLILHGSULRUWRGDWDEDVHORFN3URWRFRO
GHYLDWLRQV ZLOOEHUHYLHZHGDQGFODVVLILHGDVPLQRURUPDMRUGXULQJDGDWDUHYLHZ
PHHWLQJWKDWZLOOEHKHOGEHIRUHGDWDEDVHORFN7KHH[FOXVLRQRIVXEMHFWVIURPWKH33
SRSXODWLRQZLOOEHVSHFLILHGDQGGRFXPHQWHGLQWKH5$3
7H[WFKDQJHGWR
3HUSURWRFRO33SRSXODWLRQ DOO ,77VXEMHFWVZLWKRXWDQ\SURWRFROGHYLDWLRQV
VSHFLILFDOO\GHILQHGLQWKH5$3PDMRUYLRODWLRQVRIVWXG\SURFHGXUHV0DMRUSURWRFRO
YLRODWLRQVZLOOEHLGHQWLILHGSULRUWRGDWDEDVHORFN
3URWRFROGHYLDWLRQVZLOOEHUHYLHZHGDQGZLOOEHFODVVLILHGDVPLQRURUPDMRU LPSRUWDQW
RUQRWLPSRUWDQWGXULQJDGDWDUHYLHZPHHWLQJV WKDWZLOOEHKHOGEHIRUHGDWDEDVHORFN
7KHH[FOXVLRQRIVXEMHFWVIURPWKH33SRSXODWLRQZLOOEHVSHFLILHGDQGGRFXPHQWHGLQWKH
5$3'HYLDWLRQVFODVVLILHGDVLPSRUWDQWZLOOEHIXUWKHUGHILQHGDFFRUGLQJWR
ZKHWKHUWKH\UHTXLUHWKHSDWLHQWWREHH[FOXGHGIURPWKH33SRSXODWLRQ'HYLDWLRQV
WKDWZRXOGH[FOXGHDSDWLHQWIURPWKH33SRSXODWLRQZLOOEHGHILQHGLQWKH5$3
5DWLRQDOHIRU&KDQJH
8SGDWHGWRUHIOHFWFRUUHFWWHUPLQRORJ\
$SSHQGL[$EEUHYLDWLRQDQG7UDGHPDUNV
2ULJLQDOWH[W
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
',6.86
$&7
(//,37$
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH
$4/46
5(/9$5
(4'
6(5(7,'(
0$56$TXHVWLRQQDLUH
785%8+$/(5
3$6$34XHVWLRQQDLUH
6\PELFRUW7XUEXKDOHU
;2/$,5

2017N339371_00

2014N190259_02
&21),'(17,$/
HZA116492
141
7H[WFKDQJHGWR
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
',6.86
$&7
(//,37$
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH
$4/46
18&$/$
(4'
5(/9$5
0$56$TXHVWLRQQDLUH
6(5(7,'(
3$6$34XHVWLRQQDLUH
9,$1,
6\PELFRUW7XUEXKDOHU
785%8+$/(5
;2/$,5
785%8+$/(5
785%2+$/(5
 7XUEXKDOHUDQG7XUERKDOHUDUHERWKWUDGHQDPHV IRUWKHLQKDOHUGHYLFHXVHGIRU
6\PELFRUW7KH\DUHXVHGLQWHUFKDQJHDEO\LQWKLVGRFXPHQW
5DWLRQDOHIRU&KDQJH
7UDGHQDPHVRXWVLGHRI)UDQFH DQGWUDGHQDPHIRUPHSROL]XPDE DGGHG

2017N339371_00

2014N190259_01
&21),'(17,$/
7KH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV
HZA116492
1
7,7/(3$*(
'LYLVLRQ:RUOGZLGH'HYHORSPHQW
,QIRUPDWLRQ7\SH3URWRFRO$PHQGPHQW
7LWOH
$PRQWKRSHQODEHOUDQGRPLVHGHIILFDF\VWXG\WRHYDOXDWH
IOXWLFDVRQHIXURDWH))*:YLODQWHURO9,*:
,QKDODWLRQ3RZGHUGHOLYHUHGRQFHGDLO\YLDWKH 'U\3RZGHU
,QKDOHU(OOLSWDFRPSDUHGZLWKXVXDO,&6/$%$PDLQWHQDQFH
WKHUDS\GHOLYHUHGE\'U\3RZGHU,QKDOHULQVXEMHFWVZLWK
3HUVLVWHQW$VWKPD
&RPSRXQG1XPEHU
*:*:
'HYHORSPHQW3KDVH
,,,%
(IIHFWLYH'DWH
$8*
3URWRFRO$PHQGPHQW1XPEHU
$XWKRU V

&RS\ULJKWWKH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV$OOULJKWVUHVHUYHG
8QDXWKRULVHGFRS\LQJRUXVHRIWKLVLQIRUPDWLRQ LVSURKLELWHG

2017N339371_00
33'

2014N190259_01
&21),'(17,$/
7KH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV
HZA116492
2
5HYLVLRQ&KURQRORJ\
*OD[R6PLWK.OLQH
'RFXPHQW1XPEHU
'DWH
9HUVLRQ
1B
)(%
2ULJLQDO
1B
$8*
$PHQGPHQW1R
7KLVSURWRFRODPHQGPHQWKDVEHHQFUHDWHGWRFRUUHFWPLVWDNHV LQWKHZRUGLQJ RIWKH
LQKDOHUHUURUVTXHVWLRQQDLUHVIRUWKH(OOLSWD'LVNXV DQG7XUEXKDOHULQKDOHUVZKLFK
DUH LQFOXGHG LQ6HFWLRQ RIWKHSURWRFRO$OOUHIHUHQFHVWRµ7\SH$HUURUV¶ DQG
µRYHUDOOHUURUV¶ ZLWKLQWKHSURWRFROKDYHEHHQFKDQJHGWRµFULWLFDO¶ DQGµQRQFULWLFDO¶
HUURUVUHVSHFWLYHO\ IRUFRQVLVWHQF\ZLWKWKHLQKDOHUHUURUVTXHVWLRQQDLUHZRUNVKHHWV
6WRUDJHFRQGLWLRQLQVWUXFWLRQVIRU6HUHWLGHIOXWLFDVRQHSURSLRQDWHVDOPHWHUROLQ6HFWLRQ
KDYHEHHQ DPHQGHG
7KHZRUGLQJIRUWKHUHFRPPHQGHG QXPEHURIVSLURPHWU\HIIRUWVKDVEHHQUHYLVHG
1HZWH[WKDVEHHQLQFOXGHGZLWKUHJDUGVWRLQYHVWLJDWLRQDOSURGXFWPDOIXQFWLRQLQ
6HFWLRQ
7KHVHFRQGDU\PHGLFDOPRQLWRUFRQWDFWLQIRUPDWLRQKDVEHHQUHYLVHGWRLQFOXGHDQHZ
VWXG\SK\VLFLDQ
2WKHUPLQRUFRUUHFWLRQVDQGHGLWVKDYH EHHQPDGH

2017N339371_00


2017N339371_00
33'
33'
33'

2014N190259_01
&21),'(17,$/
HZA116492
4
0(',&$/021,7256321625,1)250$7,213$*(
0HGLFDO0RQLWRU6$(&RQWDFW,QIRUPDWLRQ
Role
1DPH
'D\7LPH 3KRQH1XPEHU
DQGHPDLODGGUHVV
$IWHUKRXUV
3KRQH&HOO
3DJHU1XPEHU
)D[
1XPEHU
6LWH$GGUHVV
3ULPDU\
0HGLFDO
0RQLWRU
&OLQLFDO
'HYHORSPHQW
3K\VLFLDQ
5'
5HVSLUDWRU\
5	'
3KRQH
(PDLO
*OD[R6PLWK.OLQH
5HVHDUFK	
'HYHORSPHQW
/LPLWHG
,URQ%ULGJH
5RDG
6WRFNOH\3DUN
:HVW8[EULGJH
0LGGOHVH[8%
%78.
6HFRQGDU\
0HGLFDO
0RQLWRU

3KRQH
(PDLO
*OD[R6PLWK.OLQH
6WRFNOH\3DUN
:HVW
,URQEULGJH
5RDG
8[EULGJH
0LGGOHVH[8%
%7
6$(
FRRUGLQDWRU


26/
3KRQH 
(PDLO
*6.)UDQFH
5RXWHGH
9HUVDLOOHV0DUO\
OH5RL
)UDQFH
6SRQVRU/HJDO5HJLVWHUHG$GGUHVV
*OD[R6PLWK.OLQH5HVHDUFK	'HYHORSPHQW/LPLWHG
*UHDW:HVW5RDG
%UHQWIRUG
0LGGOHVH[7:*6
8.
6SRQVRU&RQWDFW$GGUHVV
*OD[R6PLWK.OLQH5HVHDUFK	'HYHORSPHQW/LPLWHG
,URQ%ULGJH5RDG
6WRFNOH\3DUN:HVW8[EULGJH0LGGOHVH[8%%88.
7HOHSKRQH


2017N339371_00
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'
33'

2014N190259_01
&21),'(17,$/
HZA116492
5
6SRQVRU6HULRXV$GYHUVH(YHQWV6$(&RQWDFW,QIRUPDWLRQ
&DVH0DQDJHPHQW*URXS*&63
6WRFNOH\3DUN:HVW8[EULGJH0LGGOHVH[8%%88.
(PDLO
)D[
5HJXODWRU\$JHQF\,GHQWLI\LQJ1XPEHUV(XGUD&71R

2017N339371_00
33'
33'

2014N190259_01
&21),'(17,$/
HZA116492
6
,19(67,*$72535272&2/$*5((0(173$*(
)RUSURWRFROQXPEHU+=$
, FRQILUPDJUHHPHQWWRFRQGXFWWKHVWXG\LQFRPSOLDQFHZLWKWKHSURWRFRODVDPHQGHGE\
WKLVSURWRFRODPHQGPHQW
,DFNQRZOHGJHWKDW,DPUHVSRQVLEOHIRURYHUDOOVWXG\FRQGXFW,DJUHHWRSHUVRQDOO\
FRQGXFWRUVXSHUYLVHWKHGHVFULEHGVWXG\
,DJUHHWRHQVXUHWKDWDOODVVRFLDWHVFROOHDJXHVDQGHPSOR\HHVDVVLVWLQJLQWKHFRQGXFWRI
WKHVWXG\DUHLQIRUPHGDERXWWKHLUREOLJDWLRQV0HFKDQLVPVDUHLQSODFHWRHQVXUHWKDWVLWH
VWDIIUHFHLYHVWKHDSSURSULDWHLQIRUPDWLRQWKURXJKRXWWKHVWXG\
,QYHVWLJDWRU1DPH
,QYHVWLJDWRU$GGUHVV
,QYHVWLJDWRU3KRQH1XPEHU
,QYHVWLJDWRU6LJQDWXUH
'DWH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
7
7$%/(2)&217(176
3$*(
1.
PROTOCOL SYNOPSIS FOR STUDY HZA116492...............................................10
2.
INTRODUCTION....................................................................................................15
2.1.
Study Rationale ..........................................................................................15
2.2.
Brief Background ........................................................................................16
3.
OBJECTIVE(S) AND ENDPOINT(S) ......................................................................17
4.
STUDY DESIGN ....................................................................................................20
4.1.
Overall Design ............................................................................................20
4.2.
Treatment arms and duration......................................................................23
4.3.
Type and Number of Subjects.....................................................................23
4.4.
Design Justification.....................................................................................23
4.5.
Dose Justification........................................................................................24
4.6.
Benefit: Risk Assessment ...........................................................................24
4.6.1.
Risk Assessment .........................................................................25
4.6.1.1.
Benefit Assessment....................................................29
4.6.2.
Overall Benefit: Risk Conclusion..................................................29
5.
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA .............30
5.1.
Inclusion Criteria.........................................................................................30
5.2.
Exclusion Criteria........................................................................................32
5.3.
Screening/Baseline/Failures .......................................................................33
5.4.
Withdrawal/Stopping Criteria.......................................................................33
5.4.1.
Subjects Lost to Follow-up...........................................................33
5.4.2.
Subject Withdrawal by Investigator or Self-withdrawal .................33
5.4.3.
Liver Chemistry Stopping Criteria ................................................34
5.4.3.1.
Study Treatment Restart or Rechallenge....................36
5.4.4.
QTc Stopping Criteria ..................................................................36
5.5.
Subject and Study Completion....................................................................36
6.
STUDY TREATMENT ............................................................................................37
6.1.
Investigational Product and Other Study Treatment....................................37
6.2.
Medical Devices..........................................................................................38
6.3.
Treatment Assignment................................................................................38
6.4.
Planned Dose Adjustments.........................................................................40
6.5.
Blinding.......................................................................................................40
6.6.
Packaging and Labeling..............................................................................40
6.7.
Preparation/Handling/Storage/Accountability..............................................40
6.8.
Investigational Product Malfunction.............................................................41
6.9.
Compliance with Study Treatment Administration.......................................41
6.10.
Treatment of Study Treatment Overdose....................................................41
6.11.
Treatment after the End of the Study ..........................................................42
6.12.
Concomitant Medications and Non-Drug Therapies....................................42
6.12.1.
Permitted Medications and Non-Drug Therapies..........................42
6.12.2.
Prohibited Medications and Non-Drug Therapies.........................42
7.
STUDY ASSESSMENTS AND PROCEDURES .....................................................43

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
8
7.1.
Time and Events Table...............................................................................44
7.2.
Screening and Critical Baseline Assessments ............................................46
7.3.
Efficacy.......................................................................................................46
7.3.1.
Inhaler Correct Use Assessment .................................................46
7.3.2.
Trough (pre-dose) FEV1 assessment ..........................................49
7.3.3.
Questionnaires ............................................................................50
7.3.3.1.
Asthma Control Test (ACT) ........................................50
7.3.3.2.
Asthma Quality of Life Questionnaire (AQLQ-S).........50
7.3.3.3.
EuroQol Questionnaire (EQ-5D)-5 Level ....................50
7.3.3.4.
Medication Adherence Report Scale for 
Asthma (MARS-A)......................................................50
7.3.3.5.
Patients Satisfaction and Preference with the 
device (PASAP Questionnaire)...................................51
7.4.
Safety .........................................................................................................51
7.4.1.
Adverse Events (AE), Adverse Drug Reactions (ADRs) 
and Serious Adverse Events (SAEs)............................................51
7.4.1.1.
Time period and Frequency for collecting non 
serious ADRs and SAE information............................52
7.4.1.2.
Method of Detecting non serious ADRs and 
SAEs ..........................................................................52
7.4.1.3.
Follow-up of non serious ADRs and SAEs..................53
7.4.1.4.
Cardiovascular and Death Events ..............................53
7.4.1.5.
Disease-Related Events and/or Disease-
Related Outcomes Not Qualifying as SAEs ................53
7.4.1.6.
Regulatory Reporting Requirements for SAEs............53
7.4.2.
Pregnancy ...................................................................................54
7.4.3.
Medical Device Incidents (Including Malfunctions).......................54
7.4.4.
Physical Exams ...........................................................................54
7.4.5.
Vital Signs....................................................................................54
7.4.6.
Electrocardiogram (ECG).............................................................54
7.4.7.
Clinical Safety Laboratory Assessments ......................................55
7.5.
Genetics .....................................................................................................55
8.
DATA MANAGEMENT ...........................................................................................55
9.
STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................55
9.1.
Hypotheses.................................................................................................55
9.2.
Sample Size Considerations.......................................................................56
9.2.1.
Sample Size Assumptions ...........................................................56
9.2.2.
Sample Size Sensitivity................................................................56
9.2.3.
Sample Size Re-estimation or Adjustment...................................57
9.3.
Data Analysis Considerations .....................................................................57
9.3.1.
Analysis Populations....................................................................57
9.3.2.
Interim Analysis ...........................................................................57
9.4.
Key Elements of Analysis Plan ...................................................................57
9.4.1.
Primary Analyses.........................................................................59
9.4.2.
Secondary Analyses ....................................................................62
9.4.3.
Other Analyses ............................................................................63
10. STUDY GOVERNANCE CONSIDERATIONS........................................................67
10.1.
Posting of Information on Publicly Available Clinical Trial Registers............67

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
9
10.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................67
10.3.
Quality Control (Study Monitoring) ..............................................................67
10.4.
Quality Assurance.......................................................................................68
10.5.
Study and Site Closure ...............................................................................68
10.6.
Records Retention......................................................................................68
10.7.
Provision of Study Results to Investigators, Posting of Information 
on Publically Available Clinical Trials Registers and Publication .................69
11. REFERENCES.......................................................................................................70
12. APPENDICES........................................................................................................72
12.1.
Appendix 1: Abbreviation and Trademarks .................................................72
12.2.
Appendix 2: Study Schematic .....................................................................75
12.3.
Appendix 3: Questionnaires........................................................................76
12.4.
Appendix 4: Liver Chemistry Stopping and Follow-up Criteria.....................79
12.5.
Appendix 5: Definition of and Procedures for Recording, Evaluating, 
Follow-Up and Reporting of Adverse Events...............................................82
12.5.1.
Definition of Adverse Events and ADRs.......................................82
12.5.2.
Definition of Serious Adverse Events...........................................83
12.5.3.
Definition of Cardiovascular Events .............................................84
12.5.4.
Recording of AEs (ADRs) and SAEs............................................85
12.5.5.
Evaluating AEs (ADRs) and SAEs ...............................................86
12.5.6.
Reporting of SAEs to GSK...........................................................87
12.6.
Appendix 6: Genetic Research ...................................................................88
12.7.
Appendix 7: Collection of Pregnancy Information........................................91
12.8.
Appendix 8: Protocol Changes....................................................................92

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
10

35272&2/6<1236,6)25678'<+=$
5DWLRQDOH
7KHSLYRWDOSKDVH,,,VWXGLHVZHUHNH\WRGHPRQVWUDWHWKHVDIHW\DQGHIILFDF\RI
)OXWLFDVRQH)XURDWH9LODQWHUROLQDVWKPD+RZHYHULWLVLQFUHDVLQJO\DFNQRZOHGJHGWKDW
UDQGRPLVHGFOLQLFDOWULDOVE\GHILQLWLRQWHQGWREHKLJKO\FRQWUROOHGDQGHQURODPRUH
KLJKO\VHOHFWHGSDWLHQWSRSXODWLRQWKDQLVH[SHFWHGWREHSUHVFULEHGWKHPHGLFDWLRQSRVW
DSSURYDO7KHQHHGIRUGDWDLQDPRUHUHSUHVHQWDWLYHSRSXODWLRQLQDFORVHWRµUHDOZRUOG¶
VHWWLQJLVLQFUHDVLQJO\EHLQJUHFRJQLVHGDVLPSRUWDQWWRFRPSOHPHQWSLYRWDOSKDVH,,,
VDIHW\DQGHIILFDF\VWXGLHVLQRUGHUWRHVWDEOLVKWKHEHQHILWVDQGWKHUHIRUHWKHYDOXHRID
PHGLFDWLRQLQWKHFRQWH[WRIFOLQLFDOSUDFWLFH
0RUHRYHUGRXEOHEOLQGFRPSDULVRQRIRQFHGDLO\WRWZLFHGDLO\PHGLFLQHVZKLOH
LPSRUWDQWIRUDVVHVVLQJHIILFDF\UHPRYHVDSRWHQWLDOVRXUFHRIGLIIHUHQFHLQHIIHFWLYHQHVV
GHULYHGIURPSDWLHQWEHKDYLRXUDQGH[SHULHQFH*OD[R6PLWK.OLQH*6.KDVREVHUYHGDQ
LQFUHDVLQJGHPDQGIURPSD\HUVZKRPDNHUHLPEXUVHPHQWDQGSROLF\GHFLVLRQVIRUGDWD
WKDWHQDEOHVWKHHYDOXDWLRQRIDGUXJ
VHIIHFWLYHQHVVDQGLPSDFWRQWKHKHDOWKFDUHV\VWHP
DWODXQFKHJHIIHFWLYHQHVVGDWDIURPDVHWWLQJFORVHWR
UHDOZRUOG
LQDGGLWLRQWR
WUDGLWLRQDOUDQGRPLVHGFOLQLFDOVWXGLHV
7KLVRSHQODEHOUDQGRPLVHGFOLQLFDOVWXG\ZLOOHYDOXDWHWKHHIILFDF\DQGVDIHW\RI))9,
,QKDODWLRQ3RZGHU))PFJ9,PFJRU))PFJ9,PFJ FRPSDUHGZLWKWZR
IL[HGFRPELQDWLRQV,&6/$%$,QKDOHG&RUWLFRVWHURLGV/RQJ$FWLQJ%HWD$JRQLVWV
LQKDODWLRQSRZGHUVIOXWLFDVRQHSURSLRQDWHVDOPHWHURO)36DQGEXGHVRQLGHIRUPRWHURO
%8')IRUDVWKPDPDLQWHQDQFHWKHUDS\LQD³FORVHWRUHDOOLIH´PDQQHULQ)UHQFK
SULPDU\DQGUHVSLUDWRU\VSHFLDOLVWFDUH))9,ZLOOEHDGPLQLVWHUHGRQFHGDLO\4'YLD
(OOLSWDDQG)36RU%8')WZLFHGDLO\%,'YLD'LVNXV DQG7XUEXKDOHUUHVSHFWLYHO\
2EMHFWLYHV(QGSRLQWV
Objectives
Endpoints
Primary
!
7RFRPSDUHWKHHIILFDF\RI))9,
PFJPFJRU))PFJPFJ
ZLWKXVXDOIL[HGFRPELQDWLRQV
,&6/$%$IRUDVWKPDPDLQWHQDQFH
WKHUDS\DW:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQWKH$VWKPD
&RQWURO7HVW$&7WRWDOVFRUHDW:HHN
9LVLW
Secondary
!
7RDVVHVVHIIHFWRI))9,RQDVWKPD
FRQWUROFRPSDUHGZLWKXVXDO,&6/$%$
IL[HGFRPELQDWLRQDW:HHN9LVLW
!
7RDVVHVV(//,37$LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXV DQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
!
&KDQJHIURPEDVHOLQHLQ$&7VFRUHDW
:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVPDNLQJDWOHDVW
FULWLFDO HUURUDQGQRQFULWLFDOHUURU DW
:HHN9LVLWDQGDW:HHN9LVLW
LQGHSHQGHQWO\RIWKHXVHDW:HHN

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
11
Objectives
Endpoints
XVHDW:HHN9LVLW
9LVLW
Other
!
7RDVVHVVHIIHFWRI))9,RQWURXJKSUH
GRVH)(9FRPSDUHGZLWKXVXDO
,&6/$%$IL[HGFRPELQDWLRQDW:HHN
9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQ
UHVSRQVHWRWUHDWPHQWDW:HHN9LVLW
DQG:HHN9LVLW
!
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQDW:HHN9LVLWDQG
:HHN9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQRYHUWKHVWXG\
SHULRG
!
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIHDW:HHN
9LVLW
!
&KDQJHIURPEDVHOLQHLQWURXJKSUH
GRVH)(9DW:HHN9LVLW
!
$&7VFRUHRUSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7DW:HHN
9LVLWDQG:HHN9LVLW1RWH
$SRLQWLQFUHDVHLQ$&7WRWDOVFRUH
ZDVVXJJHVWHGDVWKH0LQLPDO
&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]
@
!
$&7VFRUHDW:HHN9LVLW
DQG:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQLQGLYLGXDO
TXHVWLRQVFRUHVIRU$&7DW:HHNV

!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN
9LVLWDQG:HHN9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
!
1XPEHURIVXEMHFWZLWKDWOHDVW
VHYHUHDVWKPDH[DFHUEDWLRQQXPEHU
RIVHYHUHDVWKPDH[DFHUEDWLRQDQG
DQQXDOVHYHUHH[DFHUEDWLRQUDWHRYHU
WKHVWXG\SHULRG
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUHDW:HHN

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
12
Objectives
Endpoints
!
7RDVVHVV3DWLHQW6DWLVIDFWLRQDQG
3UHIHUHQFHDVVHVVPHQWZLWKGLIIHUHQW
LQKDOHUV DW:HHN9LVLW
!
7RHYDOXDWHWKH6DIHW\RI))9,
FRPSDUHGZLWKXVXDO,&6/$%$)36
DQG%XG)
9LVLW
!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4VWRWDOVFRUHDW:HHN9LVLW

!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4V
HQYLURQPHQWDO
VWLPXOL
GRPDLQVFRUHDW:HHN9LVLW
!
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVH IURP EDVHOLQH RI   LQ
$4/46 ,QGLYLGXDO GRPDLQ VFRUHV DW
:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
!
+HDOWK VWDWXV XVLQJ WKH (XUR4RO
4XHVWLRQQDLUH (4' DW :HHN 
9LVLW
!
6FRUHRI3$6$34XHVWLRQQDLUH3DWLHQW
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN
9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
! )UHTXHQF\ DQG W\SH RI VHULRXV
DGYHUVHHYHQWV
! )UHTXHQF\ DQG W\SH RI QRQVHULRXV
DGYHUVH GUXJ UHDFWLRQV UHODWHG WR
WUHDWPHQW
$VHYHUHDVWKPDH[DFHUEDWLRQZLOOEHGHILQHGDVGHWHULRUDWLRQRIDVWKPDUHTXLULQJWKH
XVHRIV\VWHPLFFRUWLFRVWHURLGV WDEOHWVVXVSHQVLRQRULQMHFWLRQIRUDWOHDVWGD\VRUDQ
LQSDWLHQW KRVSLWDOLVDWLRQ RU HPHUJHQF\ GHSDUWPHQW YLVLW GXH WR DVWKPD WKDW UHTXLUHG
V\VWHPLFFRUWLFRVWHURLGV 
1RWHVGHILQLQJHQGSRLQWV
 &RQWDFWV ZLWK D GRFWRU RU KRVSLWDOLVDWLRQ DUH GHILQHG DV H[DFHUEDWLRQUHODWHG
FRQWDFWV LI WKHVH FRQWDFWV ZHUH D GLUHFW UHVXOW RI DQ DFXWH ZRUVHQLQJ RI DVWKPD
V\PSWRPV
 $SUHVFULSWLRQRIV\VWHPLFFRUWLFRVWHURLGLVGHILQHGDVH[DFHUEDWLRQUHODWHGLIWKH
UHDVRQWKHGUXJZDVJLYHQLQZKROHRULQSDUWZDVWRWUHDWDQDFXWHZRUVHQLQJRI
DVWKPDV\PSWRPV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
13
 ([DFHUEDWLRQUHODWHGKRVSLWDOLVDWLRQLQFOXGHVKRVSLWDOLVDWLRQWKDWLVSURORQJHGDVD
UHVXOWRIDQDVWKPDH[DFHUEDWLRQ
2YHUDOO'HVLJQ
7KLVLVD3KDVH,,,EPXOWLFHQWUHUDQGRPLVHGRSHQODEHOSDUDOOHOJURXSVWXG\SHUIRUPHG
LQVXEMHFWVLQSULPDU\DQGUHVSLUDWRU\VSHFLDOLVWFDUHZKRKDYHDGLDJQRVLVRIDVWKPDDQG
UHJXODUWUHDWPHQWIRU DVWKPDLQ)UDQFH
$SSUR[LPDWHO\DVWKPDWLFVXEMHFWVZKRDUHWDNLQJDQLQKDOHGFRUWLFRVWHURLG,&6
DORQHZLWKRXWDQ\RWKHUFRQWUROOHUWUHDWPHQWZLOOEHUDQGRPLVHGLQDUDWLRWRUHFHLYH
HLWKHU))9,))9,PFJPFJRU))9,PFJPFJRQFHGDLO\RURQH
,&6/$%$ LQKDODWLRQSRZGHUWZLFHGDLO\IRUDVWKPDPDLQWHQDQFHWKHUDS\
$VPXFKDVSRVVLEOHHQUROPHQWRIVXEMHFWVVKRXOGEHSHUIRUPHGDWDFRQVWDQWDFFUXDOUDWH
WKURXJKRXWDIXOO\HDULQRUGHUWRPLQLPL]HDVHDVRQDOLW\ELDV
6XEMHFWVZLOOYLVLWWKH+&3JHQHUDOSUDFWLWLRQHURUSXOPRQRORJLVWDPLQLPXPRIWLPHV
DVSHUSURWRFRORYHUDPRQWKSHULRGZKLOHSDUWLFLSDWLQJLQWKHVWXG\7KHILUVWYLVLWZLOO
EH9LVLW6FUHHQLQJ9LVLWZKLFKFDQWDNHSODFHEHWZHHQ'D\DQG'D\$W9LVLW
VXLWDEOHVXEMHFWVZLOOEHFRQVHQWHG7KHVHFRQGYLVLWZLOOEH9LVLW'D\
5DQGRPLVDWLRQ9LVLWZKHUHVXEMHFWVZKRPHHWDOORIWKH,QFOXVLRQ&ULWHULDDQGQRQHRI
WKH([FOXVLRQ&ULWHULDZLOOEHUDQGRPLVHG9LVLWDQG9LVLWFDQEHFRPELQHGLIWKH
VXEMHFWGLGQRWWDNHKLV XVXDODVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG
9LVLWDUHFRPELQHGWKHQWKLVYLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEH
FROOHFWHGDWWKLVYLVLW
$W9LVLW'D\VXEMHFWZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4
'DQG0$56$TXHVWLRQQDLUHV%DVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.$WOHDVWWKUHHYDOLGDVVHVVPHQWV
VKRXOGEHSHUIRUPHGZLWKUHJLVWUDWLRQRIWKHEHVWYDOXH2QWKHPRUQLQJRI9LVLW
VXEMHFWVZLOOQRWWDNHWKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOO
EHVWRSSHGKRXUVEHIRUHEDVHOLQHVSLURPHWU\
6XEMHFWVZLOOVHOIDGPLQLVWHUWKHLUILUVWGRVHRIVWXG\GUXJLQWKHFOLQLFDW9LVLWRUWKH
FRPELQHG9LVLWDQG9LVLWLIDSSURSULDWHXQGHUVXSHUYLVLRQRIWKHVLWHVWDII
7KHUHDIWHUHDFKVXEMHFWUDQGRPLVHGLQWRWKH))9,DUPZLOOEHLQVWUXFWHGWRVHOI
DGPLQLVWHURQHLQKDODWLRQZLWK(OOLSWD LQKDOHUHDFKGD\DWWKHVDPHWLPHRIWKHGD\DWD
WLPHWKDWLVFRQYHQLHQWIRUWKHVXEMHFW(DFKVXEMHFWZLOOEHDGYLVHGWRDGKHUHWR))9,
GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\7KHLQYHVWLJDWRUPD\DGMXVWWKHGRVHRI))9,
DFFRUGLQJWRWKHVXEMHFW¶VUHVSRQVH'RVHDGMXVWPHQWLVDOORZHGDQGLVQRWFRQVLGHUHGDV
DWUHDWPHQWIDLOXUHLQDFFRUGDQFHZLWKWUHDWPHQWIDLOXUHGHILQLWLRQ
,QDGGLWLRQHDFKVXEMHFWZKRVH))9,(OOLSWDIRUDVWKPDPDLQWHQDQFHWKHUDS\LV
LQLWLDWHGDW9LVLWZLOOEHDVNHGWRUHDGWKH LQIRUPDWLRQOHDIOHWDQGZLOOEHLQVWUXFWHGE\
WKHLQYHVWLJDWRURQWKHSURSHUXVHRI(OOLSWD(DFKVXEMHFWZKRVHXVXDO,&6/$%$'3,
'LVNXV RU7XUEXKDOHUIRUDVWKPDPDLQWHQDQFHWKHUDS\LVLQLWLDWHGDW9LVLWZLOOIROORZ
WKHVDPHSURFHGXUHUHDGLQJRIWKHLQIRUPDWLRQOHDIOHWGHPRQVWUDWLRQRIWKHSURSHUXVHRI

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
14
WKHLQKDOHUVE\WKH,QYHVWLJDWRUDQGWKHFRUUHFWGRVLQJ7KLVZLOOEHIROORZHGE\DQ
LQKDODWLRQGHPRQVWUDWLRQE\WKHSDWLHQW$Q\FULWLFDO HUURU GHILQHGDVDQHUURUWKDWLV
PRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJLQKDOHGDQGRUQRQFULWLFDO
HUURU ZLOOEHUHJLVWHUHGE\WKH,QYHVWLJDWRU
5DQGRPLVDWLRQDWWKLVYLVLWZLOOEHSHUIRUPHGRQDEDVLVWRWKH))9,IL[HGGRVH
FRPELQDWLRQGHOLYHUHGYLD(OOLSWD RUWKHLQLWLDWLRQZLWKXVXDO,&6/$%$LQKDODWLRQ
SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\
$W:HHN 9LVLWDQGDW:HHN9LVLWVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXW
ZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQVHULRXVDGYHUVH
GUXJUHDFWLRQV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJFULWLFDODQG
QRQFULWLFDO HUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRIVWXG\
GUXJ HUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQ
FDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWDWURXJKSUHGRVH)(9ZLOOEHDVVHVVHG
E\WKH,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.DQGVXEMHFWVZLOODOVREH
LQWHUYLHZHGDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ
±VHULRXVDGYHUVHGUXJUHDFWLRQV)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREH
UHPLQGHGDERXWWKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KHILQDO9LVLWZLOORFFXU DW:HHN7KH$&7$4/46(4'DQG0$56$
TXHVWLRQQDLUHVZLOOEHFRQGXFWHGDWWKLVYLVLWDQGFULWLFDODQGQRQFULWLFDOHUURUVZLWK
LQKDOHUZLOOEHUHFRUGHGIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWVXEMHFWVZLOODOVREHLQWHUYLHZHGDERXW
ZKHWKHUWKH\KDGH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJ
UHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKH
VDPHWLPHRIWKHGD\DV9LVLW
$OWKRXJKDWOHDVWIRUPDOVFKHGXOHGYLVLWVDQGSKRQHFDOOVDUHSODQQHGIRUWKLVVWXG\
VXEMHFWVVKRXOGFRQWLQXHWRYLVLWWKHLUSK\VLFLDQIRUDQ\URXWLQHQDWXUDOLVWLFYLVLWVDVSHU
QRUPDOFOLQLFDOSUDFWLFHDVSHUWKH7LPHDQG(YHQWV7DEOH$Q(DUO\:LWKGUDZDO9LVLW
KDVWREHFRQVLGHUHGLQFDVHRIHDUO\ZLWKGUDZDORIWKHVXEMHFWIURPWKHVWXG\DVSHUWKH
7LPHDQG(YHQWV7DEOH
7UHDWPHQW$UPVDQG'XUDWLRQ
7ZRWUHDWPHQWDUPVRQH))9,DUP))9,PFJPFJRU))9,PFJPFJ
RQFHGDLO\DQGRQHDUP,&6/$%$FRPELQDWLRQWKHUDS\LQLQKDODWLRQSRZGHUWZLFH
GDLO\)36PFJPFJRUPFJPFJRU%8')PFJPFJRU
PFJPFJDVGHFLGHGE\WKHSK\VLFLDQ 7KHWRWDOGXUDWLRQRIVXEMHFWSDUWLFLSDWLRQZLOO
EHDSSUR[LPDWHO\PRQWKVZHHNV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
15
7\SHDQG1XPEHURI6XEMHFWV
6XEMHFWVZLWKGRFXPHQWHGSK\VLFLDQ¶VGLDJQRVLVRIDVWKPD\HDUXQVDWLVIDFWRULO\
FRQWUROOHGDVWKPD$&7WUHDWHGE\,&6DORQHDQGLQWHQGHGWREHWUHDWHGE\
,&6/$%$PDLQWHQDQFHWKHUDS\$VXEMHFWZLOOEHHOLJLEOHIRU LQFOXVLRQLQWKLVVWXG\
RQO\LIHLWKHUDIILOLDWHGWRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDVFUHHQIDLOXUH UDWHDSSUR[LPDWHO\VXEMHFWVZLOOKDYHWREHVFUHHQHG
LQWKHVWXG\ZLWKVXEMHFWVFHQWHU
$QDO\VLV
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQHLQWKH$&7WRWDOVFRUH
DVVHVVHGDW:HHN9LVLW7KHSULPDU\VHWRIDQDO\VLVLVWKH,77SRSXODWLRQ
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHWZRVLGHGQRPLQDO
OHYHORIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,
WR,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
(YHQWKRXJKWKLVVWXG\LVRSHQODEHOWKHWHDPZLOOH[SORUHZD\VWRHQVXUHVWXG\EOLQGLV
PDLQWDLQHGGXULQJUHYLHZRIWKHGDWDDQGSUHSURJUDPPLQJ DFWLYLWLHVSULRUWRGDWDEDVH
ORFN0RUHLQIRUPDWLRQZLOOEHSURYLGHGLQWKH5$3

,1752'8&7,21

6WXG\5DWLRQDOH
,QKDOHGFRUWLFRVWHURLGV,&6DUHFRQVLGHUHGWKHPRVWHIIHFWLYHDQWLLQIODPPDWRU\
WUHDWPHQWVIRUDOOVHYHULWLHVRISHUVLVWHQWDVWKPD7KLVRSHQODEHOUDQGRPLVHGFOLQLFDO
VWXG\ZLOOHYDOXDWHWKHHIILFDF\DQGVDIHW\RIIOXWLFDVRQHIXURDWH))YLODQWHURO9,
,QKDODWLRQ3RZGHUFRPSDUHGZLWKH[LVWLQJIL[HGFRPELQDWLRQV,&6/$%$,QKDOHG
&RUWLFRVWHURLGV/RQJ$FWLQJ%HWD$JRQLVWVLQKDODWLRQSRZGHUV
)OXWLFDVRQHIXURDWH))LVDJOXFRFRUWLFRLGGHYHORSHGIRUXVHDVDRQFHGDLO\LQKDOHG
WUHDWPHQWIRUDVWKPD 9LODQWHUROLVDQRUDOO\LQKDOHGORQJDFWLQJDJRQLVWRIWKHEHWD
DGUHQRFHSWRU/$%$DQGKDVEHHQDOVRGHYHORSHGIRUXVHLQFRPELQDWLRQZLWK,&6DVD
RQFHGDLO\PDLQWHQDQFHWUHDWPHQWRIDVWKPD
7KHSLYRWDOSKDVH,,,VWXGLHVGHPRQVWUDWHGWKHVDIHW\DQGHIILFDF\RI))9,+RZHYHULW
LVLQFUHDVLQJO\DFNQRZOHGJHGWKDWUDQGRPLVHGFOLQLFDOWULDOVE\GHILQLWLRQWHQGWREH
KLJKO\FRQWUROOHGDQGHQURODPRUHKLJKO\VHOHFWHGSDWLHQWSRSXODWLRQWKDQLVH[SHFWHGWR
EHSUHVFULEHGWKHPHGLFDWLRQSRVWDSSURYDO7KHQHHGIRUGDWDLQDPRUHUHSUHVHQWDWLYH
SRSXODWLRQLQFORVHWRDµUHDOZRUOG¶VHWWLQJLVLQFUHDVLQJO\EHLQJUHFRJQLVHGDVLPSRUWDQW
WRFRPSOHPHQWSLYRWDOSKDVH,,,VDIHW\DQGHIILFDF\VWXGLHVLQRUGHUWRHVWDEOLVKWKH
EHQHILWVDQGWKHUHIRUHWKHYDOXHRIDPHGLFDWLRQLQWKHFRQWH[WRIFOLQLFDOSUDFWLFH,QGHHG
LQWKHFORVHWRµUHDOOLIH¶FRQGLWLRQVSK\VLFLDQVKDYHWKHDELOLW\WRFKRRVHWKHEHVW
WUHDWPHQWLQWKHLUYLHZIRUDQ\LQGLYLGXDO SDWLHQWDQGDGDSWWUHDWPHQWVWRVXEMHFWV¶

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
16
FKDUDFWHULVWLFVDQGUHVSRQVH7KXVGRXEOHEOLQGFRPSDULVRQRIRQFHGDLO\WRWZLFHGDLO\
PHGLFLQHVZKLOHLPSRUWDQWIRUDVVHVVLQJHIILFDF\UHPRYHVDSRWHQWLDOVRXUFHRI
GLIIHUHQFHLQHIIHFWLYHQHVVGHULYHGIURPSDWLHQWEHKDYLRXUDQGH[SHULHQFH0RUHRYHUD
KHDGWRKHDGVWXG\FRPSDULQJ5HOYDUPFJPFJ(OOLSWD ))9,RQFHDGD\YV
6HUHWLGHPFJPFJ'LVNXV )OXWLFDVRQHSURSLRQDWHVDOPHWHUROWZLFHDGD\IDLOHG
WRGHPRQVWUDWHVXSHULRULW\RQKRXUVZHLJKWHGPHDQ)(9DIWHUPRQWKVRIWUHDWPHQW
+RZHYHURIVXEMHFWVLQERWKDUPVZHUHXQFRQWUROOHG$&7VFRUHDW
UDQGRPLVDWLRQDIWHUZHHNVRI)OXWLFDVRQHSURSLRQDWHPFJWZLFHDGD\)RUWKLV
VXEJURXSRIVXEMHFWVDWWKHHQGRIWKHPRQWKWUHDWPHQWSHULRGRIVXEMHFWVZHUH
FRQWUROOHGLQWKH))9,DUPYVLQWKH6HUHWLGH'LVNXV DUP7KHVWXG\ZDVQRW
SRZHUHGRQWKLVFULWHULRQQRUGHVLJQHGWRLQFOXGHXQFRQWUROOHGVXEMHFWVRQO\$Q\ZD\
WKLVWUHQGMXVWLILHVH[SORULQJLIWKLVGLIIHUHQFHZRXOGGLVDSSHDURULQFUHDVHLQDFORVHWR
UHDOOLIHVHWWLQJ
6XEMHFWVUHFUXLWHGLQWRWKHVWXG\ZLOOEHWKRVHFXUUHQWO\WDNLQJDQ,&6DORQHZLWKRXWDQ\
RWKHUFRQWUROOHUWUHDWPHQWZLWKHYLGHQFHRIVXERSWLPDODVWKPDFRQWUROFRUUHVSRQGLQJWR
(XURSHDQ0DUNHWLQJ$XWKRULVDWLRQRI))9,7KHVHVXEMHFWVZLOOEHUDQGRPLVHGWR
UHFHLYH))9,YLD(OOLSWD LQKDOHURQFHGDLO\RUWRUHFHLYHXVXDO,&6/$%$IL[HG
FRPELQDWLRQLQ'3,IOXWLFDVRQHSURSLRQDWHVDOPHWHURO)36 YLD'LVNXV LQKDOHUDQG
EXGHVRQLGHIRUPRWHURO%8')YLD7XUEXKDOHUWZLFHGDLO\IRUDVWKPDPDLQWHQDQFH
WKHUDS\DVSHUQRUPDOFOLQLFDOSUDFWLFH (OOLSWD LVDQHZSRZGHULQKDOHUGHVLJQHGWREH
HDV\WRXVH&XUUHQWSRZGHULQKDOHUVKDYHEHHQDVVRFLDWHGZLWKKDQGOLQJHUURUVVRPHRI
ZKLFKPD\LPSDFWWKHDELOLW\RIGUXJWRUHDFKWKHOXQJDQGKHQFHLPSDFWFOLQLFDOHIILFDF\
6XFKHUURUVGHHPHGDVFULWLFDOZLOOEHHYDOXDWHGLQWKLVVWXG\EHWZHHQGLIIHUHQWLQKDOHUV
DVZHOODVRYHUDOOLQKDOHUSUHIHUHQFHDQGVDWLVIDFWLRQ

%ULHI%DFNJURXQG
$VWKPDLVDFKURQLFGLVHDVHRIWKHOXQJVFKDUDFWHULVHGE\DLUZD\LQIODPPDWLRQ
EURQFKRFRQVWULFWLRQDQGLQFUHDVHGDLUZD\UHVSRQVLYHQHVV,QKDOHGFRUWLFRVWHURLGV,&6
DUHFRQVLGHUHGWKHPRVWHIIHFWLYHDQWLLQIODPPDWRU\WUHDWPHQWVIRUDOOVHYHULWLHVRI
SHUVLVWHQWDVWKPD>*,1$1,+%ULWLVK7KRUDFLF6RFLHW\@ 7KHEHQHILWV
RI,&6LQFOXGHFRQWURORIDVWKPDV\PSWRPVLPSURYHPHQWLQOXQJIXQFWLRQGHFUHDVHLQ
DLUZD\K\SHUUHVSRQVLYHQHVVDQGSRVVLEO\SUHYHQWLRQRIDLUZD\ZDOOUHPRGHOOLQJ
>3HGHUVHQ)DQWD@
)OXWLFDVRQHIXURDWHLVDQRYHOJOXFRFRUWLFRLGGHYHORSHGIRUXVHDVDRQFHGDLO\LQKDOHG
WUHDWPHQWIRUDVWKPD7KHGUXJFRQVLVWVRI))IRUPXODWHGLQODFWRVHIRURUDOLQKDODWLRQYLD
WKH'3,(OOLSWD3UHFOLQLFDOGDWDDQGHDUO\SKDVHFOLQLFDOVWXGLHVLQGLFDWHWKDW))KDVD
ORQJHUGXUDWLRQRIDFWLRQWKDQIOXWLFDVRQHSURSLRQDWH)3DQGLVWKHUHIRUHVXLWDEOHIRU
GHYHORSPHQWIRURQFHGDLO\DGPLQLVWUDWLRQ
9LODQWHUROLVDQRUDOO\LQKDOHGORQJDFWLQJDJRQLVWRIWKHEHWDDGUHQRFHSWRU/$%$DQG
KDVEHHQGHYHORSHGIRUXVHLQFRPELQDWLRQZLWK,&6DVDRQFHGDLO\PDLQWHQDQFH
WUHDWPHQWRIDVWKPD7KHGUXJFRQVLVWVRIYLODQWHUROIRUPXODWHGLQODFWRVHDQGPDJQHVLXP
VWHDUDWHIRURUDOLQKDODWLRQYLD(OOLSWD

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
17
7KHFRPELQDWLRQRIWKHVHWZRDJHQWVKDVEHHQGHYHORSHGDVDRQFHGDLO\FRPELQDWLRQ
WKHUDS\IRUWKHORQJWHUPPDLQWHQDQFHWUHDWPHQWRIDVWKPDLQDGXOWVDQGFKLOGUHQ∀
\HDUVRIDJH7KHDYDLODELOLW\RIDRQFHGDLO\,&6FRPELQHGZLWKD/$%$ZRXOGEH
H[SHFWHGWRKHOSWRLPSURYHFRPSOLDQFHDQGWKHUHIRUHLPSURYHDVWKPDFRQWURO
,QIRUPDWLRQRQWKHSK\VLFDOFKHPLFDODQGSKDUPDFHXWLFDOSURSHUWLHVRIIOXWLFDVRQH
IXURDWHYLODQWHURODQGIOXWLFDVRQHIXURDWHYLODQWHUROPD\EHIRXQGLQ6P3&RU
,QYHVWLJDWRU%URFKXUH

2%-(&7,9(6$1'(1'32,176
7KLVRSHQODEHOUDQGRPLVHGFOLQLFDOVWXG\ZLOOHYDOXDWHWKHHIILFDF\DQGVDIHW\RI
IOXWLFDVRQHIXURDWH))YLODQWHURO9,,QKDODWLRQ3RZGHU))PFJ9,PFJRU))
PFJ9,PFJ FRPSDUHGZLWKH[LVWLQJIL[HGFRPELQDWLRQV,&6/$%$,QKDOHG
&RUWLFRVWHURLGV/RQJ$FWLQJ%HWD$JRQLVWVLQKDODWLRQSRZGHUVIOXWLFDVRQH
SURSLRQDWHVDOPHWHURO)36DQGEXGHVRQLGHIRUPRWHURO%8')IRUDVWKPD
PDLQWHQDQFHWKHUDS\LQD³FORVHWRUHDOOLIH´PDQQHULQ)UHQFKSULPDU\DQGUHVSLUDWRU\
VSHFLDOLVWFDUH))9,ZLOOEHDGPLQLVWHUHGRQFHGDLO\4'YLD(OOLSWDDQG)36RU
%8')WZLFHGDLO\%,'YLD'LVNXV DQG7XUEXKDOHUUHVSHFWLYHO\
Objectives
Endpoints
Primary
!
7RFRPSDUHWKHHIILFDF\RI))9,
PFJPFJRU))PFJPFJ
ZLWKXVXDOIL[HGFRPELQDWLRQV
,&6/$%$IRUDVWKPDPDLQWHQDQFH
WKHUDS\DW:HHN 9LVLW
!
&KDQJHIURPEDVHOLQHLQWKH$VWKPD
&RQWURO7HVW$&7WRWDOVFRUHDW:HHN
9LVLW
Secondary
!
7RDVVHVVHIIHFWRI))9,RQDVWKPD
FRQWUROFRPSDUHGZLWKXVXDO,&6/$%$
IL[HGFRPELQDWLRQDW:HHN9LVLW
!
7RDVVHVV(//,37$ LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXV DQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQ$&7VFRUHDW
:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVPDNLQJDWOHDVW
FULWLFDO HUURUDQGQRQFULWLFDOHUURU DW
:HHN9LVLWDQGDW:HHN9LVLW
LQGHSHQGHQWO\RIWKHXVHDW:HHN
9LVLW
Other
!
7RDVVHVVHIIHFWRI))9,RQSUHGRVH
WURXJK)(9FRPSDUHGZLWKXVXDO
,&6/$%$IL[HGFRPELQDWLRQDW:HHN
!
&KDQJHIURPEDVHOLQHLQSUHGRVH
WURXJK)(9DW:HHN9LVLW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
18
Objectives
Endpoints
9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQ
UHVSRQVHWRWUHDWPHQWDW:HHN9LVLW
DQG:HHN9LVLW
!
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQDW:HHN9LVLWDQG
:HHN9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQRYHUWKHVWXG\
SHULRG
!
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIHDW:HHN
9LVLW
!
$&7VFRUHRUSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7DW:HHN
9LVLWDQG:HHN9LVLW1RWH
$SRLQWLQFUHDVHLQ$&7WRWDOVFRUH
ZDVVXJJHVWHGDVWKH0LQLPDO
&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]
@
!
$&7VFRUHDW:HHN9LVLW
DQG:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQLQGLYLGXDO
TXHVWLRQVFRUHVIRU$&7DW:HHNV

!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN 
9LVLWDQG:HHN9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
!
1XPEHURIVXEMHFWZLWKDWOHDVW
VHYHUHDVWKPDH[DFHUEDWLRQQXPEHU
RIVHYHUHDVWKPDH[DFHUEDWLRQDQG
DQQXDOVHYHUHH[DFHUEDWLRQUDWHRYHU
WKHVWXG\SHULRG
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUHDW:HHN
9LVLW
!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4VWRWDOVFRUHDW:HHN9LVLW

!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4V
HQYLURQPHQWDO
VWLPXOL
GRPDLQVFRUHDW:HHN9LVLW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
19
Objectives
Endpoints
!
7RDVVHVV3DWLHQW6DWLVIDFWLRQDQG
3UHIHUHQFHDVVHVVPHQWZLWKGLIIHUHQW
LQKDOHUV DW:HHN9LVLW
!
7RHYDOXDWHWKH6DIHW\ RI))9,
FRPSDUHGZLWKXVXDO,&6/$%$)36
DQG%XG)
!
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVH IURP EDVHOLQH RI   LQ
$4/46 ,QGLYLGXDO GRPDLQ VFRUHV DW
:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
!
+HDOWK VWDWXV XVLQJ WKH (XUR4RO
4XHVWLRQQDLUH (4' DW :HHN 
9LVLW
!
6FRUHRI3$6$34XHVWLRQQDLUH3DWLHQW
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN
9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
! )UHTXHQF\ DQG W\SH RI VHULRXV
DGYHUVHHYHQWV
! )UHTXHQF\ DQG W\SH RI QRQVHULRXV
DGYHUVH GUXJ UHDFWLRQV UHODWHG WR
WUHDWPHQW
$ VHYHUHDVWKPDH[DFHUEDWLRQZLOOEHGHILQHGDVGHWHULRUDWLRQRIDVWKPDUHTXLULQJWKH
XVHRIV\VWHPLFFRUWLFRVWHURLGV WDEOHWVVXVSHQVLRQRULQMHFWLRQIRUDWOHDVWGD\VRUDQ
LQSDWLHQW KRVSLWDOLVDWLRQ RU HPHUJHQF\ GHSDUWPHQW YLVLW GXH WR DVWKPD WKDW UHTXLUHG
V\VWHPLFFRUWLFRVWHURLGV 
1RWHVGHILQLQJHQGSRLQWV
 &RQWDFWV ZLWK D GRFWRU RU KRVSLWDOLVDWLRQ DUH GHILQHG DV H[DFHUEDWLRQUHODWHG
FRQWDFWV LI WKHVH FRQWDFWV ZHUH D GLUHFW UHVXOW RI DQ DFXWH ZRUVHQLQJ RI DVWKPD
V\PSWRPV
 $SUHVFULSWLRQRIV\VWHPLFFRUWLFRVWHURLGLVGHILQHGDVH[DFHUEDWLRQUHODWHGLIWKH
UHDVRQWKHGUXJZDVJLYHQLQZKROHRULQSDUWZDVWRWUHDWDQDFXWHZRUVHQLQJRI
DVWKPDV\PSWRPV
 ([DFHUEDWLRQUHODWHGKRVSLWDOLVDWLRQLQFOXGHVKRVSLWDOLVDWLRQWKDWLVSURORQJHGDVD
UHVXOWRIDQDVWKPDH[DFHUEDWLRQ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
20

678'<'(6,*1

2YHUDOO'HVLJQ
7KLVLVD3KDVH,,,EPXOWLFHQWHUUDQGRPLVHGRSHQODEHOSDUDOOHOJURXSVWXG\SHUIRUPHG
LQVXEMHFWVLQ)UHQFKSULPDU\DQGUHVSLUDWRU\FDUHVSHFLDOLVWZKRKDYHDGLDJQRVLVRI
DVWKPDDQGDUHJXODUWUHDWPHQWIRU SHUVLVWHQWDVWKPD6XEMHFWVZLWKXQVDWLVIDFWRULO\
FRQWUROOHGDVWKPDGHILQHGDVDQ$&7DQGLQWHQGHGWREHWUHDWHGE\XVXDO
,&6/$%$PDLQWHQDQFHWKHUDS\WRVHHNDEHWWHUFRQWURORIWKHLUDVWKPDZLOOEH
UDQGRPLVHGWRUHFHLYHHLWKHU))9,))9,PFJPFJRU))9,PFJPFJRQFH
GDLO\RUDQRWKHUXVXDO,&6/$%$FRPELQDWLRQWKHUDS\LQLQKDODWLRQSRZGHUWZLFHGDLO\
)36RU%8')GHFLGHGE\WKHSK\VLFLDQ7KHVHPHGLFDWLRQVDUHUHFRUGHGLQWKHH&5)
3K\VLFLDQVZLOOEHDOORZHGGXULQJWKHWUHDWPHQWSHULRGWRDGDSWSUHVFULSWLRQWRGLIIHUHQW
GRVHVLIQHFHVVDU\DVZHOODVWRDGDSWGRVHVRIDQ\FRPSDUDWLYHWUHDWPHQWDFFRUGLQJWR
SURGXFWVODEHO$WDEOH7DEOH 6HFWLRQRIWKHLQGLFDWLYHGRVDJHHTXLYDOHQFH
EHWZHHQ,&6DQGWKHRWKHUFRPELQDWLRQWKHUDSLHVZLOOEHSURYLGHGWRWKHSK\VLFLDQV
)RU6WXG\6FKHPDWLFVHH$SSHQGL[
,QYHVWLJDWRUV
*HQHUDO3UDFWLWLRQHUVDQGSXOPRQRORJLVWVEDVHGLQ)UDQFHDOODFFUHGLWHGIRUFOLQLFDOWULDOV
E\D&33³&RPLWpGH3URWHFWLRQGHV3HUVRQQHV´ZLOOEHDSSURDFKHGWRSDUWLFLSDWHLQWKH
VWXG\DSSUR[LPDWHO\*HQHUDO3UDFWLWLRQHUVSXOPRQRORJLVWV
6FUHHQLQJUDQGRPLVDWLRQDQGIROORZXS
$WWKH6FUHHQLQJ9LVLWHOLJLEOHVXEMHFWVZLOOEHFRQVHQWHGWRSDUWLFLSDWHWRWKHWULDODQG
SUHVFULEHGWKHQHFHVVDU\H[DPLQDWLRQV7KHVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWR
WKH$&7$VFUHHQLQJORJZLOOEHSHUIRUPHGDWWKLVYLVLW
$WDIXUWKHUYLVLWLH9'D\RFFXUULQJZLWKLQZHHNDIWHUWKHVFUHHQLQJYLVLW9
VXEMHFWVZKRPHHWDOORIWKH,QFOXVLRQ&ULWHULDQRQHRIWKH([FOXVLRQ&ULWHULDDQGZKR
DFFHSWWRJLYHWKHLUFRQVHQWZLOOEHUDQGRPLVHGLQWKHVWXG\5DQGRPLVDWLRQDWWKLVYLVLW
ZLOOEHRQDEDVLVWRWKH))9,IL[HGGRVHFRPELQDWLRQGHOLYHUHGE\(OOLSWD RUWRWKH
LQLWLDWLRQRIWKHXVXDO,&6/$%$'3,IRUDVWKPDPDLQWHQDQFHWKHUDS\FKRVHQE\WKH
SK\VLFLDQ9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLVXVXDO
DVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG9LVLWDUHFRPELQHG WKHQWKLV
YLVLWZLOOEH'D\
$W9LVLW5DQGRPLVDWLRQYLVLW'D\EDVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGE\WKH
,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.$WOHDVWWKUHHDVVHVVPHQWVVKRXOGEH
SHUIRUPHGZLWKUHJLVWUDWLRQRIWKHEHVWYDOXH$WOHDVWWZRRIWKHVSLURPHWU\HIIRUWV
VKRXOGEHDFFHSWDEOHDQGUHSHDWDEOH2QWKHPRUQLQJRI9LVLWVXEMHFWVZLOOQRWWDNH
WKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHGKRXUV
EHIRUHEDVHOLQHVSLURPHWU\

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
21
,QDGGLWLRQDW9LVLW VXEMHFWVZLOOEHDVNHGWRUHDGWKHZULWWHQ(OOLSWD SDFNDJHLQVHUWLI
UDQGRPLVHGLQWRWKH))9,DUPRU'LVNXV RU7XUEXKDOHULIUDQGRPLVHGLQWKHXVXDO
,&6/$%$WKHUDS\DUPDQGZLOOEHLQVWUXFWHGE\WKHLQYHVWLJDWRURQWKHSURSHUXVHRI
LQKDOHUV7KHQ WKHVXEMHFWZLOOVHOIDGPLQLVWHUWKHLUILUVWGRVHRIVWXG\GUXJXQGHU
VXSHUYLVLRQRIWKHLQYHVWLJDWRU$Q\FULWLFDOHUURUGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\
WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJLQKDOHGRUQRQFULWLFDOHUURU ZLOOEH
UHJLVWHUHGE\WKHWUDLQHG+&3$IWHUFRPSOHWLQJWKHSURFHGXUHVXEMHFWVZLOOEHLQVWUXFWHG
LQWKHFRUUHFWXVHRIWKHGHYLFHE\WKHWUDLQHGSK\VLFLDQLIQHHGHG7KHUHDIWHUHDFK
VXEMHFWUDQGRPLVHGLQWRWKH))9,DUPZLOOEHLQVWUXFWHGWRVHOIDGPLQLVWHURQHLQKDODWLRQ
ZLWK(OOLSWD LQKDOHUHDFKGD\DWWKHVDPHWLPHRIWKHGD\DWDWLPHWKDWLVFRQYHQLHQWIRU
WKHVXEMHFW6XEMHFWUDQGRPLVHGLQWRXVXDO,&6/$%$WKHUDS\DUPZLOOEHLQVWUXFWHGWR
VHOIDGPLQLVWHUWKHLQKDODWLRQZLWK'LVNXV RU7XUEXKDOHULQKDOHUWZLFHDGD\
6XEMHFWVZLOOEHUHFRPPHQGHGWRXVH6DOEXWDPRODVQHHGHGWKURXJKRXWWKHVWXG\IRU
UHOLHIRIWKHLUDVWKPDV\PSWRPV$W9LVLWUDQGRPLVDWLRQ'D\VXEMHFWZLOOEHDVNHG
WRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
$W:HHN 9LVLWDQGDW:HHN9LVLWVXEMHFWVZLOOEHWHOHSKRQHGE\WKH
,QYHVWLJDWRUWRHQTXLUHDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVHHYHQWV
RQO\WKHVHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQVZLOOEHUHFRUGHGLQ
H&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRWWRVWXG\
WUHDWPHQW$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJFULWLFDODQG
QRQFULWLFDO HUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRIVWXG\
GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQ
FDVHRIPXOWLSOHHUURUVGHWHFWLRQ3UHGRVHWURXJK)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJWKHVSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPRO
ZLOOEHVWRSSHGKRXUVEHIRUHWKHVSLURPHWU\$WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOGEH
SHUIRUPHGZLWKUHJLVWUDWLRQRIWKHEHVWYDOXH $WWKLVYLVLWVXEMHFWVZLOODOVREH
LQWHUYLHZHGE\WKH,QYHVWLJDWRUDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVH
HYHQWVRQO\WKHVHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQVZLOOEH
UHFRUGHGLQH&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRW
WRVWXG\WUHDWPHQW)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREHUHPLQGHGDERXW
WKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KHILQDO9LVLWZLOORFFXU DW:HHN7KH$&7$4/46(4'DQG0$56$
TXHVWLRQQDLUHVZLOOEHFRQGXFWHGDWWKLVYLVLWDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\
UHFRUGLQJFULWLFDODQGQRQFULWLFDO HUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQ
RIRQHGRVHRIVWXG\GUXJE\VXEMHFWHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRU
GHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ6XEMHFWVZLOO
EHLQWHUYLHZHGDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRU
QRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUW
WRVFKHGXOH9LVLWDWWKHVDPHWLPHRIWKHGD\DV9LVLW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
22
$OWKRXJKDWOHDVWIRUPDOVFKHGXOHGYLVLWVDQGSKRQHFDOOVDUHSODQQHGIRUWKLVVWXG\
VXEMHFWVVKRXOGFRQWLQXHWRYLVLWWKHLUSK\VLFLDQIRUDQ\URXWLQHQDWXUDOLVWLFYLVLWVDVSHU
QRUPDOFOLQLFDOSUDFWLFHDVSHUWKH7LPHDQG(YHQWV7DEOH6HFWLRQ$Q(DUO\
:LWKGUDZDO9LVLWKDVWREHFRQVLGHUHG LQFDVHRIHDUO\ZLWKGUDZDORIWKHVXEMHFWIURPWKH
VWXG\DVSHUWKH7LPHDQG(YHQWV7DEOH6HFWLRQ
3URWRFROZDLYHUVRUH[HPSWLRQVDUHQRWDOORZHGZLWKWKHH[FHSWLRQRILPPHGLDWHVDIHW\
FRQFHUQV7KHUHIRUHDGKHUHQFHWRWKHVWXG\GHVLJQUHTXLUHPHQWVLQFOXGLQJWKRVH
VSHFLILHGLQWKH7LPHDQG(YHQWV7DEOHDUHHVVHQWLDODQGUHTXLUHGIRUVWXG\FRQGXFW
6XSSOHPHQWDU\VWXG\FRQGXFWLQIRUPDWLRQQRWPDQGDWHGWREHSUHVHQWLQWKLVSURWRFROLV
SURYLGHGLQWKHDFFRPSDQ\LQJ6WXG\3URFHGXUHV0DQXDO6307KH630ZLOOSURYLGH
WKHVLWHSHUVRQQHOZLWKDGPLQLVWUDWLYHDQGGHWDLOHGWHFKQLFDOLQIRUPDWLRQWKDWGRHVQRW
LPSDFWVXEMHFWVDIHW\
2XWFRPHGHVFULSWLRQ
2QHRIWKHPDLQFKDOOHQJHVRIWKLVVWXG\SHUIRUPHGLQVRFDOOHGµFORVHWRUHDOOLIHVHWWLQJ¶
LVWRREWDLQGDWDRQVXEMHFWVZLWKPLQLPDOLQWHUIHUHQFHZLWKWKHDFWXDOSUDFWLFHRI
PHGLFLQH7KXVGXULQJWKHPRQWKVWUHDWPHQWSHULRGRIWKHVWXG\DOOLQWHUYHQWLRQVZLOO
EHUHFRUGHGDVSHUQRUPDO7KH\ZLOOEHFDSWXUHGE\VHYHUDOPHDQV

3K\VLFLDQVSDUWLFLSDWLQJLQWKHVWXG\ZLOOEHDVNHGWRILOOLQDQHOHFWURQLF&5)
H&5)IRFXVHGRQFOLQLFDOGDWDDWVFUHHQLQJYLVLW9LVLWDWUDQGRPLVDWLRQ
9LVLWDW:HHN9LVLWDWWKHHQGRIWKHVWXG\DW:HHN9LVLWDQGDW
WZRSKRQHFDOOVDW:HHN9LVLWDQGDW:HHN9LVLW

$W:HHN DQGDW:HHNVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXWZKHWKHU
WKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVHHYHQWVDQGWKHQWKHLQYHVWLJDWRUFDOOLQJ
WKHSDWLHQWPXVWGHWHUPLQHZKHWKHUWKHHYHQWLVUHODWHGWRVWXG\PHGLFDWLRQHLWKHU
DUPDQGZKHWKHUWKHHYHQWLVVHULRXV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVR
EHDVNHGE\WKH,QYHVWLJDWRUWRFRPSOHWHWKH$&7TXHVWLRQQDLUHDQGWRVHQGLW
EDFNWRWKH,QYHVWLJDWRU

:KHQQHFHVVDU\LQIRUPDWLRQZLOOEHREWDLQHGIURPRWKHUPHGLFDOVRXUFHV
QDWXUDOLVWLFYLVLWV
7KHYDULDEOHVRILQWHUHVWZLOOEHGRFXPHQWHGE\DFRPELQDWLRQRILQIRUPDWLRQFROOHFWHG
IURPDOOWKHVHVRXUFHV
&ROOHFWHGGDWD
(OLJLEOHVXEMHFWVZLOOFRPSOHWHWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
DW5DQGRPLVDWLRQ9LVLW9LVLW'D\DQGDW9LVLW:HHNRUDWWKH(DUO\
:LWKGUDZDOYLVLW$&7TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRE\WKHVXEMHFWDW6FUHHQLQJ
YLVLW9LVLW:HHNSKRQHFDOORU9LVLWDW:HHN9LVLWDQG:HHNSKRQH
FDOORU9LVLW0$56$TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRDW:HHN9LVLW
,QKDOHUXVHDVVHVVPHQWZLOOEHSHUIRUPHGDW5DQGRPLVDWLRQ9LVLW9LVLW'D\DW
:HHN9LVLWDQGDW:HHN9LVLW(DUO\:LWKGUDZDOYLVLWE\UHFRUGLQJWKH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
23
FULWLFDODQGQRQFULWLFDO HUURUV3DWLHQW¶VVDWLVIDFWLRQDQGSUHIHUHQFH3$6$34ZLOOEH
HYDOXDWHGDW:HHN9LVLW
%DVHOLQHVSLURPHWU\ZLOOEHSHUIRUPHGDW5DQGRPLVDWLRQ9LVLW9LVLW'D\DQGDW
:HHN9LVLWE\WKH,QYHVWLJDWRUXVLQJWKHVSLURPHWHUSURYLGHGE\*6.LQRUGHUWR
DVVHVVSUHGRVHWURXJK)(9DW:HHN9LVLW
)RUWKH6WXG\6FKHPDWLFVHH$SSHQGL[ DQG6HFWLRQ IRUWKHSURSRVHGWLPHDQG
HYHQWVWDEOH

7UHDWPHQWDUPVDQGGXUDWLRQ
5DQGRPLVDWLRQZLOOEHRQDEDVLV ZLWKWZRWUHDWPHQWDUPVRQH))9,DUP))9,
PFJPFJRU))9,PFJPFJRQFHGDLO\DQGRQHDUP,&6/$%$FRPELQDWLRQ
WKHUDS\LQ LQKDODWLRQSRZGHUWZLFHGDLO\)36PFJPFJRUPFJPFJRU
%8')PFJPFJRUPFJPFJDVGHFLGHGE\WKHSK\VLFLDQ 7KHWRWDO
GXUDWLRQRIVXEMHFWSDUWLFLSDWLRQZLOOEHDSSUR[LPDWHO\PRQWKVZHHNV$VPXFKDV
SRVVLEOHHQUROPHQWRIVXEMHFWVVKRXOGEHSHUIRUPHGDWDFRQVWDQWDFFUXDOUDWHWKURXJKRXW
DIXOO\HDULQRUGHUWRPLQLPL]HDVHDVRQDOLW\ELDV

7\SHDQG1XPEHURI6XEMHFWV
6XEMHFWVZLWKGRFXPHQWHGSK\VLFLDQ¶VGLDJQRVLVRIDVWKPD\HDUXQVDWLVIDFWRULO\
FRQWUROOHGDVWKPD$&7WUHDWHGE\,&6DORQHDQGLQWHQGHGWREHWUHDWHGE\
,&6/$%$PDLQWHQDQFHWKHUDS\$VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\
RQO\LIHLWKHUDIILOLDWHGWRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDVFUHHQIDLOXUH UDWHDSSUR[LPDWHO\VXEMHFWVZLOOKDYHWREHVFUHHQHG
LQWKHVWXG\ZLWKVXEMHFWVFHQWHU
6XEMHFWVZLWKGUDZQIURPWKHVWXG\ZLOOQRWEHUHSODFHG

'HVLJQ-XVWLILFDWLRQ
$QRSHQODEHOGHVLJQLVDSSURSULDWHIRUVXFKDVWXG\EHFDXVHLWLVDFRPSDULVRQRI
EHQHILWVDQGULVNVRI))9,YHUVXVXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\LQFORVH
WRUHDOOLIHVHWWLQJ
3UHYLRXVVWXGLHVKDYHGHPRQVWUDWHGWKDWLPSURYHPHQWVLQ$&7VFRUHFDQEHVHHQLQ
SHULRGVRIPRQWKVPDNLQJWKLVVXLWDEOHWLPHIUDPHWRDVVHVV$&7FKDQJHV
7KHWUHDWPHQWGXUDWLRQRIPRQWKVZHHNVLQWKLVVWXG\LVFRQVLGHUHGVXIILFLHQWWR
GHPRQVWUDWHHIILFDF\LQWKHSURSRVHGVWXG\SRSXODWLRQ
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQHLQWKH$&7WRWDOVFRUH
DVVHVVHGDW:HHN9LVLW7KHDLPZLOOEHWRSURYHQRQLQIHULRULW\RI))9,WRDQ\
RWKHU,&6/$%$FRPSDUDWRU7KHK\SRWKHVLVRIQRQLQIHULRULW\ZLOOEHILUVWWHVWHGDW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
24
:HHN,IDQGRQO\LIQRQLQIHULRULW\LVVLJQLILFDQWO\DFKLHYHGDW:HHNQRQ
LQIHULRULW\ZLOOWKHQEHWHVWHGDW:HHN,IDQGRQO\LIQRQLQIHULRULW\LVDFKLHYHGDWD
YLVLWWKHQVXSHULRULW\RI))9,WRDQ\RWKHUFRPSDUDWRUZLOOEHWHVWHGDWWKLVYLVLW:HHN
RU:HHN

'RVH-XVWLILFDWLRQ
7ZRVWUHQJWKVRI))9,KDYHEHHQDSSURYHGPFJPFJGHOLYHUHGGRVHRI
PFJPFJIRUPRGHUDWHSHUVLVWHQWDVWKPD DQGPFJPFJ GHOLYHUHGGRVHRI
PFJPFJIRUVHYHUHSHUVLVWHQWDVWKPD7KHGRVHRIPFJPFJZLOOEH
SUHIHUHQWLDOO\SURJUHVVHGLQWKLVVWXG\DVWKLVGRVHVWUHQJWKLVOLNHO\WRPHHWWKHQHHGVRI
PRVWVXEMHFWV+RZHYHUSK\VLFLDQVZLOOEHDOORZHGWRFKDQJHWKHSUHVFULSWLRQWRKLJKHU
GRVHDFFRUGLQJWRVXEMHFW¶VUHVSRQVHZLWKRXWH[FHHGLQJWKHPD[LPXPDOORZHGGRVH

%HQHILW5LVN $VVHVVPHQW
6XPPDULHVRIILQGLQJVIURPERWKFOLQLFDODQGQRQFOLQLFDOVWXGLHVFRQGXFWHGZLWK))9,
FDQEHIRXQGLQWKH,QYHVWLJDWRU¶V%URFKXUH,%RU6XPPDU\RI3URGXFW&KDUDFWHULVWLFV
6P3&7KHIROORZLQJVHFWLRQRXWOLQHVWKHULVNDVVHVVPHQWDQGPLWLJDWLRQVWUDWHJ\IRU
WKLVSURWRFRO

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
25

5LVN$VVHVVPHQW
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
6HULRXV&DUGLRYDVFXODU(YHQWV
7KLVLVDSRWHQWLDOFODVVHIIHFWRI/$%$V,Q
FOLQLFDOVWXGLHVSHUFHQWDJHVRIVXEMHFWVZLWK
IDWDOHYHQWVWKDWZHUHFDUGLRYDVFXODULQ
QDWXUHZHUHVLPLODUDFURVVDOO WUHDWPHQW
JURXSVWR
6XEMHFWVZLWKKLVWRULFDORUFXUUHQWHYLGHQFH
RIXQFRQWUROOHGRUFOLQLFDOO\VLJQLILFDQW
GLVHDVHDUHH[FOXGHGIURPWKHVWXG\
&DUGLRYDVFXODUPHGLFDOKLVWRU\&9ULVN
IDFWRUVDQGH[DFHUEDWLRQKLVWRU\ZLOOEH
DVVHVVHGDVGHVFULEHGLQWKHWLPHDQGHYHQWV
WDEOH
$VWKPDUHODWHGLQWXEDWLRQVDQGGHDWKV
7KLVLVDSRWHQWLDOFODVVHIIHFWRI/$%$V,W
ZDVQRWREVHUYHGLQSUHFOLQLFDOVWXGLHVZLWK
))9,'XULQJWKH))9,VWXGLHVIRUWKH
DVWKPDFRPSRVLWHHQGSRLQWDVWKPD
H[DFHUEDWLRQVOHDGLQJWRKRVSLWDOL]DWLRQ
LQWXEDWLRQDQGRUGHDWKWKHUHZDVQR
VLJQLILFDQWGLIIHUHQFH
EHWZHHQWKH))9,JURXSDQGWKH,&6JURXS
RU QRQ/$%$JURXSGHPRQVWUDWLQJQR
LQFUHDVHGULVNZKHQDGGLQJD/$%$WRDQ
,&6
6XEMHFWVZLWKDKLVWRU\RIOLIHWKUHDWHQLQJ
DVWKPDDUHH[FOXGHGIURPWKLVVWXG\
6XEMHFWVDUHH[FOXGHGIURPWKLVVWXG\LIWKH\
KDYHDVHYHUHDQGXQVWDEOHDVWKPDZLWK
$&7 VFRUHKLVWRU\RIUHSHDWHGVHYHUH
H[DFHUEDWLRQV\HDUDQGRUH[DFHUEDWLRQ
LQWKHSUHYLRXVZHHNV
6XEMHFWVDUHH[FOXGHGIURP WKLVVWXG\LIWKH\
DUHXVLQJ/$%$ZLWKRXWDQ,&6DVDVWKPD
PDLQWHQDQFHWKHUDS\



2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
26
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
+\SHUVHQVLWLYLW\
7KHUHSRUWHGK\SHUVHQVLWLYLW\HYHQWVLQ
FOLQLFDOWULDOVZHUHQRWJHQHUDOO\VHULRXV
GLGQRWOHDGWRGLVFRQWLQXDWLRQLQWKH
VWXGLHVDQGZHUHXVXDOO\FRQIRXQGHGE\
HLWKHUWKHVXEMHFW¶VPHGLFDOFRQGLWLRQVXFK
DV&23'RURWKHUIDFWRUVDWWKHWLPHRIWKH
HYHQW
,QVSRQWDQHRXVGDWDV\PSWRPVRI
K\SHUVHQVLWLYLW\UDQJHGIURPPLOGUDVKDQG
SUXULWLVWRVHYHUHJHQHUDOLVHGUDVKDQG
HU\WKHPDDQGVHYHUHFDVHVLQYROYLQJ
DQJLRGHPDRIWKHIDFHODU\Q[DQGSKDU\Q[
7KHVHHYHQWVZHUHUDUH
6XEMHFWV ZLWKDKLVWRU\ RIDGYHUVHUHDFWLRQ
LQFOXGLQJ
LPPHGLDWH
RU
GHOD\HG
K\SHUVHQVLWLYLW\ WR DQ\ LQWUDQDVDO LQKDOHG
RU V\VWHPLF FRUWLFRVWHURLG DQG /$%$
WKHUDS\DQGWRFRPSRQHQWVRIWKHLQKDODWLRQ
SRZGHU HJ ODFWRVH PDJQHVLXP VWHDUDWH
ZLOOEHH[FOXGHG,QDGGLWLRQVXEMHFWVZLWK
DKLVWRU\RIVHYHUHPLONSURWHLQDOOHUJ\WKDW
LQ
WKH
RSLQLRQ
RI
WKH
,QYHVWLJDWRU
FRQWUDLQGLFDWHV WKH VXEMHFW¶V SDUWLFLSDWLRQ
ZLOODOVREHH[FOXGHG
6\VWHPLFHIIHFWVRIFRUWLFRVWHURLGVDGUHQDO
VXSSUHVVLRQH\HGLVRUGHUVGHFUHDVHGERQH
GHQVLW\DQGDVVRFLDWHGIUDFWXUHV
$GUHQDOVXSSUHVVLRQLVDNQRZQFODVVHIIHFW
RIFRUWLFRVWHURLGV3UHFOLQLFDOVWXGLHV
VKRZHGWKDW))HIIHFWVDUHFRPSDUDEOHZLWK
RWKHUFRUWLFRVWHURLGV1RVWXGLHVKDYH
VKRZQDFOLQLFDOO\UHOHYDQWHIIHFWRI))9,
RQWKHK\SRWKDODPLFSLWXLWDU\D[LV+3$
7KLVLQFOXGHVDIRUPDO+3$VWXG\
+=$XVLQJKRXUVHUXPFRUWLVRO
PHDVXUHPHQWVDQGPXOWLSOHVWXGLHVZLWK
&23'DQGDVWKPDVXEMHFWVZKLFK
PRQLWRUHGXULQDU\FRUWLVRO'XULQJFOLQLFDO
7KHPLWLJDWLRQLQWKLVVWXG\IRUDOOV\VWHPLF
HIIHFWV RI FRUWLFRVWHURLGV LV WKDW FKURQLF
XVHUV
RI
V\VWHPLF
FRUWLFRVWHURLGV
DUH
H[FOXGHGIURPWKLVVWXG\DVXEMHFWZKRLQ
WKHRSLQLRQRIWKH,QYHVWLJDWRULVFRQVLGHUHG
WR
EH
D
FKURQLF
XVHU
RI
V\VWHPLF
FRUWLFRVWHURLGV IRU UHVSLUDWRU\ RU RWKHU
LQGLFDWLRQV LI XQVXUH GLVFXVV ZLWK WKH
PHGLFDOPRQLWRUSULRUWRVFUHHQLQJ ZLOOEH
H[FOXGHG



2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
27
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
GHYHORSPHQWQRHYHQWVRI$GUHQDO
6XSSUHVVLRQZHUHUHSRUWHG
(\HGLVRUGHUVDUHDNQRZQFODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDOVWXGLHVVKRZHG
))DWKLJKGRVHFRPSDUDEOHWRRWKHUKLJK
GRVHFRUWLFRVWHURLGV,QVWXG\+=$
))9,))DQG)3LQVXEMHFWVZLWKDVWKPD
IRUPDORSKWKDOPLFDVVHVVPHQWVZHUH
FRQGXFWHGLQFOXGLQJ/2&6,,,HYDOXDWLRQV
IRURFXODURSDFLWLHVWKURXJKRXWWKHVWXG\
7KLVVWXG\VKRZHGQRDSSDUHQWHIIHFWVRQ
OHQVRSDFLILFDWLRQFRPSDUHG WREDVHOLQH
'XULQJVWXGLHVLQERWKVXEMHFWVZLWKDVWKPD
DQG&23'QRDVVRFLDWHGDIIHFWRQRFXODU
GLVRUGHUVZDVREVHUYHG
'HFUHDVHGERQHGHQVLW\LVDNQRZQFODVV
HIIHFWRIFRUWLFRVWHURLGV3UHFOLQLFDOGDWD
VKRZHGWKDWKLJKGRVHFRUWLFRVWHURLGHIIHFWV
RI))ZHUHFRPSDUDEOHWRRWKHU
FRUWLFRVWHURLGV3DWLHQWVZLWK$VWKPD,QDQ
LQWHJUDWHGDQDO\VLVRIVWXGLHVLQDVWKPD
SDWLHQWVWKHLQFLGHQFHRIIUDFWXUHV
ZLWK))9,ZDV DQGXVXDOO\
DVVRFLDWHGZLWKWUDXPD



2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
28
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Procedures
6SLURPHWU\SURFHGXUHV
6KRUWQHVVRIEUHDWKFRXJKLQJOLJKW
KHDGHGQHVVRUIDLQWLQJDQGRUFKHVW
WLJKWQHVV
,IDQ\RIWKHVHV\PSWRPVVKRXOGKDSSHQWR
WKHVXEMHFWVSLURPHWU\ZLOOEHVWRSSHGDQG
KHVKHZLOOUHFHLYHPHGLFDOWUHDWPHQW
Other 
6XPPDULHVRIILQGLQJVIURPERWKFOLQLFDODQGQRQFOLQLFDOVWXGLHVFRQGXFWHGZLWKFRPSDUDWRUV6HUHWLGH'LVNXVDQG6\PELFRUW
7XUEXKDOHUFDQEHIRXQGLQWKH6XPPDU\RI3URGXFW&KDUDFWHULVWLFV6P3&



2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
29

%HQHILW$VVHVVPHQW
&RPELQHGWUHDWPHQWZLWK,&6DQG/$%$KDVEHHQVKRZQWREHPRUHHIIHFWLYHWKDQWKH
LQGLYLGXDOFRPSRQHQWVLQDVWKPDOHDGLQJWRWKHGHYHORSPHQWRIIL[HGGRVHFRPELQDWLRQ
LQKDOHUV7KHXVHRI,&6/$%$FRPELQDWLRQVLVQRZZHOOHVWDEOLVKHGLQLQWHUQDWLRQDO
WUHDWPHQWJXLGHOLQHVIRUPRGHUDWHWRVHYHUHSHUVLVWHQWDVWKPDSDWLHQWVIRUZKRP
WUHDWPHQWZLWK,&6DORQHLVQRWVXIILFLHQW
%RWKIOXWLFDVRQHSURSLRQDWHVDOPHWHURODQGEXGHVRQLGHIRUPRWHUROIXPDUDWHDUH
FRPPHUFLDOO\DYDLODEOHSURGXFWVIRUWKHWUHDWPHQWRISHUVLVWHQWDVWKPDDQGKDYH
UHFRJQL]HGVDIHW\SURILOHV%RWKRIWKHVHSURGXFWVDUHDGPLQLVWHUHGWZLFHGDLO\

2YHUDOO%HQHILW5LVN&RQFOXVLRQ
7KHLQYHVWLJDWLRQDOSURGXFW,3))9,KDVDQDFFHSWDEOH VDIHW\SURILOHIRU FOLQLFDOXVH
DQGWKHUHDUHQRVLJQLILFDQWDVVRFLDWHGULVNV7KLVFRQFOXVLRQLVVXSSRUWHGWKHUHVXOWVRI
SUHYLRXVO\SHUIRUPHGFOLQLFDOVWXGLHVZLWKWKHSURGXFWVLQKHDOWK\ YROXQWHHUVDQGVXEMHFWV
ZLWK$VWKPDDQG&23'*OD[R6PLWK.OLQH'RFXPHQW1XPEHU 50
$GYHUVHHIIHFWVWKDWFRXOGEHDVVRFLDWHGZLWKWKHXVHRI))9,ZLOO EHFORVHO\PRQLWRUHG
$VDIHW\FULWHULRQRXWOLQLQJGHWDLOVIRUVXEMHFWZLWKGUDZDOLV LQFOXGHGLQWKHSURWRFRO
6HFWLRQ :LWKGUDZDO&ULWHULD$WKRURXJKVXPPDU\DQG HYDOXDWLRQRIWKHDYDLODEOH
SUHFOLQLFDOGDWDFDQEHIRXQGLQWKH,%>*OD[R6PLWK.OLQH 'RFXPHQW1XPEHU
50@5RXWLQHVDIHW\DQDO\VLVRIWKLVVWXG\ZLOOEH FRQGXFWHGE\WKH
FRPSDQ\ 7DNLQJLQWRDFFRXQWWKHPHDVXUHVWDNHQWRPLQLPL]HULVNWRVXEMHFWV
SDUWLFLSDWLQJLQWKLV VWXG\WKHSRWHQWLDOULVNVLGHQWLILHGLQDVVRFLDWLRQZLWK))9,DUH
MXVWLILHGE\WKHDQWLFLSDWHGEHQHILWV WKDWPD\EHDIIRUGHGWRSDWLHQWVZLWKDVWKPD

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
30

6(/(&7,212)678'<3238/$7,21$1'
:,7+'5$:$/&5,7(5,$
6SHFLILFLQIRUPDWLRQUHJDUGLQJZDUQLQJVSUHFDXWLRQVFRQWUDLQGLFDWLRQVDGYHUVHHYHQWV
DQGRWKHUSHUWLQHQWLQIRUPDWLRQRQWKH*6.LQYHVWLJDWLRQDOSURGXFW RURWKHUVWXG\
WUHDWPHQWWKDWPD\LPSDFWVXEMHFWHOLJLELOLW\LVSURYLGHGLQWKH,%,%VXSSOHPHQWVRU
WKH6P3&DQGRWKHUSHUWLQHQWGRFXPHQWV

,QFOXVLRQ&ULWHULD
'HYLDWLRQVIURPLQFOXVLRQFULWHULDDUHQRWDOORZHGEHFDXVHWKH\FDQSRWHQWLDOO\MHRSDUGLVH
WKHVFLHQWLILFLQWHJULW\RIWKHVWXG\UHJXODWRU\DFFHSWDELOLW\RUVXEMHFWVDIHW\7KHUHIRUH
DGKHUHQFHWRWKHFULWHULDDVVSHFLILHGLQWKHSURWRFROLVHVVHQWLDO
6XEMHFWVHOLJLEOHIRUHQUROPHQWLQWKHVWXG\PXVWPHHWDOORIWKHIROORZLQJFULWHULD

,QIRUPHG FRQVHQW &DSDEOH RI JLYLQJ VLJQHG LQIRUPHG FRQVHQW DV GHVFULEHG LQ
6HFWLRQ ZKLFKLQFOXGHVFRPSOLDQFHZLWKWKHUHTXLUHPHQWVDQGUHVWULFWLRQVOLVWHG
LQWKHFRQVHQWIRUPDQGLQWKLVSURWRFRO

*HQGHUDQG$JH0DOHRUIHPDOHVXEMHFWVDJHG∀DQG\HDUVRIDJHDW9LVLW
)HPDOHVXEMHFWLVHOLJLEOHWRSDUWLFLSDWHLIVKHLVQRWSUHJQDQWDVFRQILUPHGE\DQHJDWLYH
XULQHKXPDQFKRULRQLFJRQDGRWURSKLQ>K&*@ WHVWQRWODFWDWLQJDQGDWOHDVWRQHRIWKH
IROORZLQJFRQGLWLRQVDSSOLHV
D
1RQUHSURGXFWLYHSRWHQWLDOGHILQHGDV
!
3UHPHQRSDXVDOIHPDOHVZLWKRQHRIWKHIROORZLQJ
!
'RFXPHQWHGWXEDOOLJDWLRQ
!
'RFXPHQWHGK\VWHURVFRSLFWXEDORFFOXVLRQSURFHGXUHZLWKIROORZ
XSFRQILUPDWLRQRIELODWHUDOWXEDORFFOXVLRQ
!
+\VWHUHFWRP\
!
'RFXPHQWHG%LODWHUDO2RSKRUHFWRP\
!
3RVWPHQRSDXVDOGHILQHGDVPRQWKVRIVSRQWDQHRXVDPHQRUUKHD>LQ
TXHVWLRQDEOHFDVHVDEORRGVDPSOHZLWKVLPXOWDQHRXVIROOLFOHVWLPXODWLQJ
KRUPRQH)6+DQGHVWUDGLROOHYHOVFRQVLVWHQWZLWKPHQRSDXVHUHIHUWR
ODERUDWRU\UHIHUHQFHUDQJHVIRUFRQILUPDWRU\OHYHOV@)HPDOHVRQKRUPRQH
UHSODFHPHQWWKHUDS\+57DQGZKRVHPHQRSDXVDOVWDWXVLVLQGRXEWZLOOEH
UHTXLUHGWRXVHRQHRIWKHKLJKO\HIIHFWLYHFRQWUDFHSWLRQPHWKRGVLIWKH\ZLVKWR
FRQWLQXHWKHLU+57GXULQJWKHVWXG\2WKHUZLVHWKH\PXVWGLVFRQWLQXH+57WR
DOORZFRQILUPDWLRQRISRVWPHQRSDXVDOVWDWXVSULRUWRVWXG\HQUROPHQW
E
5HSURGXFWLYHSRWHQWLDODQGDJUHHVWRIROORZRQHRIWKHRSWLRQVOLVWHGEHORZLQWKH
*6.0RGLILHG/LVWRI+LJKO\(IIHFWLYH0HWKRGVIRU$YRLGLQJ3UHJQDQF\LQ
)HPDOHVRI5HSURGXFWLYH3RWHQWLDO)53UHTXLUHPHQWVIURPGD\VSULRUWRWKH
ILUVWGRVHRIVWXG\PHGLFDWLRQDQGXQWLO:HHN9LVLW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
31
*6.0RGLILHG/LVWRI+LJKO\(IIHFWLYH0HWKRGVIRU$YRLGLQJ3UHJQDQF\LQ)HPDOHV
RI5HSURGXFWLYH3RWHQWLDO)53
7KLVOLVWGRHVQRWDSSO\WR)53ZLWKVDPHVH[SDUWQHUVZKHQWKLVLVWKHLUSUHIHUUHGDQG
XVXDOOLIHVW\OHRUIRUVXEMHFWVZKRDUHDQGZLOOFRQWLQXHWREHDEVWLQHQWIURPSHQLOH
YDJLQDOLQWHUFRXUVHRQDORQJWHUPDQGSHUVLVWHQWEDVLV

&RQWUDFHSWLYHVXEGHUPDOLPSODQWWKDWPHHWVWKH623HIIHFWLYHQHVVFULWHULD
LQFOXGLQJDUDWHRIIDLOXUHSHU\HDUDVVWDWHGLQWKHSURGXFWODEHO

,QWUDXWHULQHGHYLFHRULQWUDXWHULQHV\VWHPWKDWPHHWVWKH623HIIHFWLYHQHVVFULWHULD
LQFOXGLQJDUDWHRIIDLOXUHSHU\HDUDVVWDWHGLQWKHSURGXFWODEHO>+DWFKHU
D@

2UDO&RQWUDFHSWLYHHLWKHUFRPELQHGRUSURJHVWRJHQDORQH>+DWFKHUD@

,QMHFWDEOHSURJHVWRJHQ>+DWFKHUD@

&RQWUDFHSWLYHYDJLQDOULQJ>+DWFKHUD@

3HUFXWDQHRXVFRQWUDFHSWLYHSDWFKHV>+DWFKHUD@

0DOHSDUWQHUVWHULOL]DWLRQZLWKGRFXPHQWDWLRQRID]RRVSHUPLDSULRUWRWKHIHPDOH
VXEMHFW
VHQWU\LQWRWKHVWXG\DQGWKLVPDOHLVWKHVROHSDUWQHUIRUWKDWVXEMHFW
>+DWFKHUD@

0DOHFRQGRPFRPELQHGZLWKDYDJLQDOVSHUPLFLGHIRDPJHOILOPFUHDPRU
VXSSRVLWRU\>+DWFKHUE@

7KHVHDOORZHGPHWKRGVRIFRQWUDFHSWLRQDUHRQO\HIIHFWLYHZKHQXVHG
FRQVLVWHQWO\FRUUHFWO\DQGLQDFFRUGDQFHZLWKWKHSURGXFWODEHO7KHLQYHVWLJDWRU
LVUHVSRQVLEOHIRUHQVXULQJWKDWVXEMHFWVXQGHUVWDQGKRZWRSURSHUO\XVHWKHVH
PHWKRGVRIFRQWUDFHSWLRQ

7\SHRIVXEMHFW
D
6XEMHFWV ZLWK GRFXPHQWHG SK\VLFLDQ¶V GLDJQRVLV RI DVWKPD   \HDU
XQVDWLVIDFWRULO\FRQWUROOHGDVWKPD$&7DW9LVLWDQG9LVLWWUHDWHGE\
,&6DORQHDQGLQWHQGHGWREHWUHDWHGE\,&6/$%$PDLQWHQDQFHWKHUDS\
E
$VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\RQO\LIHLWKHUDIILOLDWHGWRRUD
EHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\

&XUUHQW $VWKPD 7KHUDS\ $OO VXEMHFWV PXVW EH SUHVFULEHG PDLQWHQDQFH WKHUDS\
DQG UHFHLYLQJ ,&6 DORQH ZLWKRXW /$%$ IRU DW OHDVW  ZHHNV SULRU WR 9LVLW 
5DQGRPLVDWLRQYLVLW
2WKHU EDFNJURXQG DVWKPD PHGLFDWLRQ VXFK DV DQWLOHXNRWULHQHV RU WKHRSK\OOLQH LV
SHUPLWWHG DV DQ DOWHUQDWLYH WR ,&6 DORQH LI LQLWLDWHG DW OHDVW  ZHHNV SULRU WR
VFUHHQLQJYLVLW9LVLW
 6XEMHFW TXHVWLRQQDLUHV 6XEMHFWV PXVW EH DEOH WR FRPSOHWH WKH TXHVWLRQQDLUHV
WKHPVHOYHV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
32

([FOXVLRQ&ULWHULD
'HYLDWLRQV IURP H[FOXVLRQ FULWHULD DUH QRW DOORZHG EHFDXVH WKH\ FDQ SRWHQWLDOO\
MHRSDUGLVHWKHVFLHQWLILFLQWHJULW\RIWKHVWXG\UHJXODWRU\DFFHSWDELOLW\RUVXEMHFWVDIHW\
7KHUHIRUHDGKHUHQFHWRWKHFULWHULDDVVSHFLILHGLQWKHSURWRFROLVHVVHQWLDO
6XEMHFWVPHHWLQJDQ\RIWKHIROORZLQJFULWHULDPXVWQRWEHHQUROOHGLQWKHVWXG\
 +LVWRU\RI/LIHWKUHDWHQLQJDVWKPD 'HILQHGIRUWKLVSURWRFRODVDQDVWKPDHSLVRGH
WKDWUHTXLUHGLQWXEDWLRQDQGRUZDVDVVRFLDWHGZLWKK\SHUFDSQHDUHVSLUDWRU\DUUHVWRU
K\SR[LFVHL]XUHVZLWKLQWKHODVWPRQWKV EHIRUH9LVLWDQG9LVLW
 6XEMHFWVKDYLQJDVHYHUHDQGXQVWDEOHDVWKPD ZLWK$&7 VFRUHDW9LVLWDQG
DW 9LVLW  KLVWRU\ RI UHSHDWHG VHYHUH H[DFHUEDWLRQV \HDU DQGRU D VHYHUH
H[DFHUEDWLRQLQWKHSUHYLRXVZHHNVEHIRUH9LVLWDQG9LVLW

&23'5HVSLUDWRU\'LVHDVH$VXEMHFWPXVWQRWKDYHFXUUHQWHYLGHQFHRUGLDJQRVLV
RIFKURQLFREVWUXFWLYH SXOPRQDU\GLVHDVHDW9LVLW

&XUUHQWRUIRUPHUFLJDUHWWHVPRNHUV ZLWKDKLVWRU\RIFLJDUHWWHVPRNLQJRI
SDFN\HDUVDWVFUHHQLQJ9LVLW>QXPEHURISDFN\HDUV QXPEHURIFLJDUHWWHVSHU
GD\[QXPEHURI\HDUVVPRNHGHJFLJDUHWWHVSHUGD\IRU\HDUVRU
FLJDUHWWHVSHUGD\IRU\HDUV@
 2WKHU GLVHDVHVDEQRUPDOLWLHV 6XEMHFWV ZLWK KLVWRULFDO RU FXUUHQW HYLGHQFH RI
XQFRQWUROOHGRUFOLQLFDOO\VLJQLILFDQWGLVHDVHDW9LVLWDQGDW9LVLW6LJQLILFDQWLV
GHILQHGDVDQ\GLVHDVHWKDWLQWKHRSLQLRQRIWKH,QYHVWLJDWRUZRXOGSXWWKHVDIHW\RI
WKHVXEMHFWDWULVNWKURXJKSDUWLFLSDWLRQRUZKLFKZRXOGDIIHFWWKHHIILFDF\RUVDIHW\
DQDO\VLVLIWKHGLVHDVHFRQGLWLRQH[DFHUEDWHGGXULQJWKHVWXG\
 6XEMHFWV ZLWK D KLVWRU\ RI DGYHUVH UHDFWLRQ LQFOXGLQJ LPPHGLDWH RU GHOD\HG
K\SHUVHQVLWLYLW\ WR DQ\ LQWUDQDVDO LQKDOHG RU V\VWHPLF FRUWLFRVWHURLG DQG /$%$
WKHUDS\ DQG WR FRPSRQHQWV RI WKH LQKDODWLRQ SRZGHU HJ ODFWRVH PDJQHVLXP
VWHDUDWHDW9LVLWDQGDW9LVLW,QDGGLWLRQVXEMHFWVZLWKDKLVWRU\RIVHYHUHPLON
SURWHLQDOOHUJ\WKDWLQWKHRSLQLRQRIWKH,QYHVWLJDWRUFRQWUDLQGLFDWHVWKHVXEMHFW¶V
SDUWLFLSDWLRQZLOODOVREHH[FOXGHG
 ,QYHVWLJDWLRQDO0HGLFDWLRQV$VXEMHFWPXVWQRWKDYHXVHGDQ\LQYHVWLJDWLRQDOGUXJ
ZLWKLQ  GD\V SULRU WR 9LVLW  RU ZLWKLQ ILYH KDOIOLYHV Wò RI WKH SULRU
LQYHVWLJDWLRQDO VWXG\ ZKLFKHYHU LV ORQJHU RI WKH WZR LI XQVXUH GLVFXVV ZLWK WKH
PHGLFDOPRQLWRUSULRUWRVFUHHQLQJ
 &KURQLF XVHU RI V\VWHPLF FRUWLFRVWHURLGV $ VXEMHFW ZKR LQ WKH RSLQLRQ RI WKH
,QYHVWLJDWRU LV FRQVLGHUHG WR EH D FKURQLF XVHU RI V\VWHPLF FRUWLFRVWHURLGV IRU
UHVSLUDWRU\RURWKHULQGLFDWLRQVLIXQVXUHGLVFXVVZLWKWKHPHGLFDOPRQLWRUSULRUWR
VFUHHQLQJDW9LVLW
 6XEMHFWV WUHDWHG E\ WKH PRQRFORQDO DQWLERG\ RPDOL]XPDE ;RODLU DW 9LVLW 
7UHDWPHQWZLWK;RODLULVQRWDOORZHGGXULQJWKHVWXG\
 6XEMHFWV LQYROYHGLQRWKHUFOLQLFDOWULDOVDW9LVLW
 $IILOLDWLRQ ZLWK ,QYHVWLJDWRU 6LWH ,V DQ LQYHVWLJDWRU VXELQYHVWLJDWRU VWXG\
FRRUGLQDWRU HPSOR\HH RI D SDUWLFLSDWLQJ LQYHVWLJDWRU RU VWXG\ VLWH RU LPPHGLDWH
IDPLO\PHPEHURIWKHDIRUH PHQWLRQHGWKDWLVLQYROYHGLQWKLVVWXG\

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
33
 6XEMHFWVZKRSODQWRPRYHDZD\IURPWKHJHRJUDSKLFDODUHDZKHUHWKHVWXG\LV
EHLQJFRQGXFWHGGXULQJWKHVWXG\

6FUHHQLQJ%DVHOLQH)DLOXUHV
$SSUR[LPDWHO\  VXEMHFWV ZLOO EH VFUHHQHG DV  VXEMHFWV DUH SODQQHG WR EH
UDQGRPLVHGDQGDVFUHHQIDLOXUH UDWH LVH[SHFWHG
!
6FUHHQIDLOXUHVDUHGHILQHGDVVXEMHFWVZKRFRQVHQWWRSDUWLFLSDWHLQWKHFOLQLFDO
WULDOEXWDUHQHYHUVXEVHTXHQWO\UDQGRPL]HG ,QRUGHUWRHQVXUHWUDQVSDUHQW
UHSRUWLQJRIVFUHHQIDLOXUHVXEMHFWVPHHWWKH&RQVROLGDWHG 6WDQGDUGVRI
5HSRUWLQJ7ULDOV&216257SXEOLVKLQJUHTXLUHPHQWVDQGUHVSRQGWRTXHULHV
IURP5HJXODWRU\DXWKRULWLHVDPLQLPDOVHWRIVFUHHQIDLOXUHLQIRUPDWLRQLV
UHTXLUHGLQFOXGLQJ'HPRJUDSK\6FUHHQ)DLOXUHGHWDLOV(OLJLELOLW\&ULWHULDDQG
DQ\6HULRXV$GYHUVH(YHQWVUHODWHGWRVWXG\SDUWLFLSDWLRQ

:LWKGUDZDO6WRSSLQJ&ULWHULD

6XEMHFWV/RVWWR)ROORZXS
7KHIROORZLQJDFWLRQVPXVWEHWDNHQLQUHODWLRQWRDVXEMHFWZKRIDLOVWRDWWHQGWKHFOLQLF
IRUDUHTXLUHGVWXG\YLVLW
!
7KHVLWHPXVWDWWHPSWWRFRQWDFWWKHVXEMHFWDQGUHVFKHGXOHWKHPLVVHGYLVLWDVVRRQ
DVSRVVLEOH
!
7KHVLWHPXVWFRXQVHOWKHVXEMHFWRQWKHLPSRUWDQFHRIPDLQWDLQLQJWKHDVVLJQHGYLVLW
VFKHGXOHDQGDVFHUWDLQZKHWKHURUQRWWKHVXEMHFWZLVKHVWRDQGRUVKRXOGFRQWLQXHLQ
WKHVWXG\
!
,QFDVHVZKHUHWKHVXEMHFWLVGHHPHGµORVWWRIROORZXS¶WKHLQYHVWLJDWRURUGHVLJQHH
PXVWPDNHHYHU\HIIRUWWRUHJDLQFRQWDFWZLWKWKHVXEMHFWZKHUHSRVVLEOH
WHOHSKRQHFDOOVDQGLIQHFHVVDU\DFHUWLILHGOHWWHUWRWKHVXEMHFW¶VODVWNQRZQPDLOLQJ
DGGUHVV RUORFDOHTXLYDOHQWPHWKRGV7KHVHFRQWDFWDWWHPSWVVKRXOGEHGRFXPHQWHG
LQWKHVXEMHFW¶VPHGLFDOUHFRUG
!
6KRXOGWKHVXEMHFWFRQWLQXHWREHXQUHDFKDEOHRQO\WKHQZLOOKHVKHEHFRQVLGHUHGWR
KDYHZLWKGUDZQIURPWKHVWXG\ZLWKDSULPDU\UHDVRQRI³/RVWWR)ROORZXS´

6XEMHFW:LWKGUDZDOE\,QYHVWLJDWRURU6HOIZLWKGUDZDO
6XEMHFWVPD\EHZLWKGUDZQIURPVWXG\WUHDWPHQWDWDQ\WLPHE\WKH,QYHVWLJDWRULILWLV
FRQVLGHUHGWREHGHWULPHQWDOIRUWKHPWRFRQWLQXHWKHVWXG\WUHDWPHQWRUPD\GLVFRQWLQXH
DVXEMHFWIURPWKHVWXG\DWKLVRUKHUGLVFUHWLRQ,IDVXEMHFWZLWKGUDZVIURPWKHVWXG\
KHVKHPD\UHTXHVWGHVWUXFWLRQRIDQ\VDPSOHVWDNHQDQGWKHLQYHVWLJDWRUPXVWGRFXPHQW
WKLVLQWKHVLWHVWXG\UHFRUGV
7KHIROORZLQJFULWHULDZLOOFDXVHDVXEMHFWWREHZLWKGUDZQIURPLQYHVWLJDWLRQDO
SURGXFW,3EXWHYHU\HIIRUWVKRXOGEHPDGHWRNHHSWKH6XEMHFWLQWKHVWXG\
!
$VXEMHFWEHFRPHVSUHJQDQW
!
$VXEMHFWPHHWVWKH/LYHU6WRSSLQJ&ULWHULDDVGHILQHGLQ6HFWLRQ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
34
!
$VXEMHFWPHHWVWKH47FVWRSSLQJFULWHULDDVGHILQHGLQ6HFWLRQ
,IWKHVXEMHFWFKRRVHVWRZLWKGUDZIURPWKHVWXG\DOOVWXG\UHODWHGPHGLFDWLRQVDQGRWKHU
VWXG\UHODWHGPDWHULDOVVKRXOGEHUHWXUQHGWRWKHVLWH E\WKHVXEMHFW$Q(DUO\:LWKGUDZDO
9LVLWVKRXOGEHFRQGXFWHGZLWKLQKRXUVRIWKHVXEMHFWVWRSSLQJVWXG\PHGLFDWLRQ
6HFWLRQ 7LPHDQG(YHQW7DEOH,QWKHHYHQWDVXEMHFWZLWKGUDZVDWRUGXULQJD
VFKHGXOHGYLVLWDQ(DUO\:LWKGUDZDO9LVLWLVQRWUHTXLUHGKRZHYHUDOOVWXG\SURFHGXUHV
VFKHGXOHGDWDQ(DUO\:LWKGUDZDO9LVLWPXVWEHSHUIRUPHGDWWKLVYLVLWLQVWHDG
7KHSULPDU\UHDVRQIRUVWXG\WUHDWPHQWGLVFRQWLQXDWLRQRUVWXG\ZLWKGUDZDOZLOOEH
UHFRUGHGLQWKHHOHFWURQLF&DVH5HSRUW)RUPH&5)DQGDQ\GDWDFROOHFWHGXSXQWLOWKH
SRLQWRIZLWKGUDZDOZLOOEHXVHGLQWKHGDWDDQDO\VHV
6SHFLILFUHJDUGVKRXOGEHJLYHQWRGLVWLQJXLVKLQJZLWKGUDZDOVGXHWR$'5V 6$(VDQG
SURWRFRO GHYLDWLRQ IROORZLQJ FRQVXOWDWLRQ ZLWK WKH PHGLFDO PRQLWRU 7KH ,QYHVWLJDWRU
ZLOOUHFRUGWKHSULPDU\UHDVRQLQWKHH&5)
6XEMHFWVZLWKGUDZQIURPWKHVWXG\ZLOOQRWEHUHSODFHG
6XEMHFWV ZKR H[SHULHQFH DQ DVWKPD H[DFHUEDWLRQ GXULQJ WKH 7UHDWPHQW 3HULRG FDQ
FRQWLQXHLQWKHVWXG\DWWKH GLVFUHWLRQRIWKHLU,QYHVWLJDWRU

/LYHU&KHPLVWU\6WRSSLQJ&ULWHULD
/LYHUFKHPLVWU\VWRSSLQJDQGLQFUHDVHGPRQLWRULQJFULWHULD KDYHEHHQGHVLJQHGWR
DVVXUHVXEMHFWVDIHW\DQGHYDOXDWHOLYHUHYHQW HWLRORJ\ LQDOLJQPHQWZLWKWKH)'$
SUHPDUNHWLQJFOLQLFDOOLYHUVDIHW\JXLGDQFH
KWWSZZZIGDJRYGRZQORDGV'UXJV*XLGDQFH&RPSOLDQFH5HJXODWRU\,QIRUPDWLRQ*XLG
DQFHV8&0SGI

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
35
3KDVH,,,,9/LYHU&KHPLVWU\6WRSSLQJDQG,QFUHDVHG0RQLWRULQJ$OJRULWKP
Continue Study Treatment 
Discontinue Study Treatment 
3OXV
Bilirubin≥2x
ULN (>35% 
direct) RUSOXV
INR>1.5, if 
measured*
3RVVLEOH
+\¶V /DZ
ALT≥3xULN
ALT
≥8xULN
3OXV
Symptoms of 
liver injury
or 
hypersensitivity
No
Yes
Yes
Yes
No
No
No
See algorithm 
for continued 
therapy with 
increased liver 
chemistry 
monitoring
Yes
*INR value not applicable to subjects on anticoagulants 
ALT 
≥3xULN 
but 
<8xULN
Yes
 0XVWUHIHUWR/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWVVHFWLRQLQWKH$SSHQGL[
 5HSRUWDVDQ6$(LISRVVLEOH+\¶V /DZFDVHALT≥3xULN DQGBilirubin≥2xULN (>35% direct)  RU
INR>1.5, if measured*
3KDVH,,,,9/LYHU&KHPLVWU\,QFUHDVHG0RQLWRULQJ$OJRULWKP ZLWK&RQWLQXHG
7KHUDS\IRU$/7∀[8/1EXW[8/1
Continue Study Treatment   and   Monitor Liver Chemistry
Discontinue Study Treatment 
ALT≥5xULN 
but <8xULN
+ bili <2xULN +
no symptoms
No
 0XVWUHIHUWR/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWVVHFWLRQLQWKH$SSHQGL[
Yes
ALT ≥3xULN 
but <5xULN
+ bili <2xULN  +
no symptoms
Able to 
monitor  
weekly 
for  ≥2 
weeks
Persists for 
≥2 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
No
No
Able to 
monitor  
weekly 
for  ≥4 
weeks
Persists for 
≥4 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
Yes
ALT ≥5xULN 
ALT <5xULN 
Yes
Yes
*INR value not applicable to subjects on anticoagulants 
 0XVWUHIHUWR/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWVVHFWLRQLQWKH$SSHQGL[
 5HSRUWDVDQ6$(LISRVVLEOH+\¶V /DZFDVHALT≥3xULN DQGBilirubin≥2xULN (>35% direct)  RU
INR>1.5, if measured*

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
36
/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWV6HFWLRQFDQEHIRXQGLQ
$SSHQGL[

6WXG\7UHDWPHQW5HVWDUWRU 5HFKDOOHQJH
6WXG\WUHDWPHQWUHVWDUWRUUHFKDOOHQJHDIWHUOLYHUFKHPLVWU\VWRSSLQJFULWHULDPHWE\DQ\
VXEMHFWSDUWLFLSDWLQJLQWKLVVWXG\LVQRWDOORZHG

47F6WRSSLQJ&ULWHULD
$Q(&*LVQRWUHTXLUHGSULRUWRHQWHULQJWKLVVWXG\7KHUHDUHQRRWKHUUHJXODU(&*V
UHTXLUHGE\WKLVSURWRFRO,IKRZHYHUZKLOHDVXEMHFWLVUHFHLYLQJVWXG\PHGLFDWLRQDQ
(&*LVSHUIRUPHGDVSDUWRIWKHQRUPDOFOLQLFDOSUDFWLFHDQGDSURORQJHG47LQWHUYDOLV
GHWHFWHG WKH IROORZLQJ DVVHVVPHQWV IRU ZLWKGUDZDO IURP WKH VWXG\ DUH UHTXLUHG DIWHU
GLVFXVVLRQEHWZHHQ,QYHVWLJDWRUDQGWKHPHGLFDOPRQLWRU
)RUDOOVXEMHFWV
$VXEMHFWZKRPHHWVHLWKHURIWKHEXOOHWHGFULWHULDEHORZZLOOEHZLWKGUDZQIURPWKH
VWXG\
!
47F!PVHF258QFRUUHFWHG 47!PVHF
!
,QFUHDVHLQ47F!PVHFGHWHFWHGFRPSDUHGWRDSUHYLRXV(&*
)RUSDWLHQWVZLWKXQGHUO\LQJEXQGOHEUDQFKEORFNIROORZWKHGLVFRQWLQXDWLRQFULWHULD
OLVWHGEHORZ
%DVHOLQH47FZLWK%XQGOH%UDQFK%ORFN
'LVFRQWLQXDWLRQ47FZLWK%XQGOH
%UDQFK%ORFN
PVHF
!PVHF
± PVHF
PVHF
7KH47FVKRXOGEHEDVHGRQVLQJOHRUDYHUDJHG47FYDOXHVRIWULSOLFDWH
HOHFWURFDUGLRJUDPVREWDLQHGRYHUDEULHIHJPLQXWHUHFRUGLQJSHULRG

6XEMHFWDQG6WXG\&RPSOHWLRQ
$FRPSOHWHGVXEMHFWLVRQHZKRKDVFRPSOHWHGDOOVWXG\YLVLWV7KHHQGRIWKHVWXG\LV
GHILQHGDVWKHODVWVXEMHFW¶VODVWYLVLW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
37

678'<75($70(17

,QYHVWLJDWLRQDO3URGXFWDQG2WKHU6WXG\7UHDWPHQW
7KHWHUPµVWXG\WUHDWPHQW¶LVXVHGWKURXJKRXWWKHSURWRFROWRGHVFULEHDQ\FRPELQDWLRQ
RISURGXFWVUHFHLYHGE\WKHVXEMHFWDVSHUWKHSURWRFROGHVLJQ6WXG\WUHDWPHQWPD\
WKHUHIRUHUHIHUWRWKHLQGLYLGXDOVWXG\WUHDWPHQWVRUWKHFRPELQDWLRQRIWKRVHVWXG\
WUHDWPHQWV
$OOVXEMHFWVZLOOUHFHLYHWKHDVWKPDPHGLFDWLRQWREHXVHGGXULQJWKHVWXG\IURPWKH
LQYHVWLJDWRUVLWH
*OD[R6PLWK.OLQH&OLQLFDO7ULDOV6XSSOLHVZLOOSURYLGHWKHLQYHVWLJDWLRQDOSURGXFWV
))9,5HOYDU (OOLSWD DQGFRPSDUDWLYHWUHDWPHQWVLH6HUHWLGH 'LVNXV
6\PELFRUW 7XUEXKDOHUDVZHOODVUHVFXHPHGLFDWLRQ6DOEXWDPROIRUXVHLQWKLVVWXG\
1HZ,&6/$%$'3,RU'3,FRSLHVRIH[LVWLQJPDUNHWHG,&6/$%$LIDQ\LQ)UDQFHDW
WKHWLPHRIWKHVWXG\ZLOOQRWEHFRQVLGHUHGLQWKLVWULDO
(DFKVXEMHFWUDQGRPLVHGWRWKH))9,DUPZLOOEHLQVWUXFWHGWRDGPLQLVWHUWKHVWXG\
PHGLFDWLRQRQFHGDLO\E\UHDGLQJWKHOHDIOHWDQGGHPRQVWUDWLRQRILWXVHDWWKHVDPH
WLPHRIWKHGD\IRUWKHGXUDWLRQRIWKHWUHDWPHQWSHULRG(DFKVXEMHFWZLOOEHDGYLVHGWR
DGKHUHWR))9,GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\7KH,QYHVWLJDWRUPD\DGMXVWWKH
GRVHRI))9,DFFRUGLQJWRWKHVXEMHFWV¶UHVSRQVHVWDUWLQJE\))9,PFJPFJ
(DFKVXEMHFWLQLWLDWLQJRWKHU,&6/$%$PDLQWHQDQFHWKHUDS\ZLOOEHUHPLQGHGDERXWWKH
WHFKQLTXHVRIKRZWRXVHWKHLUPDLQWHQDQFHPHGLFDWLRQE\UHDGLQJWKHOHDIOHWDQG
GHPRQVWUDWLRQRILWXVHDQGWKHFRUUHFWGRVLQJ(DFKVXEMHFWZLOOEHDGYLVHGWRDGKHUHWR
,&6/$%$GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\VWDUWLQJE\)36PFJPFJRUE\
%8')PFJPFJDFFRUGLQJWRWKH,QYHVWLJDWRU¶VGHFLVLRQ7KH,QYHVWLJDWRUPD\
DGMXVWWKHGRVHRIHDFKSURGXFWDFFRUGLQJWRWKHVXEMHFWV¶UHVSRQVH
$GHVFULSWLRQRIWKHLQYHVWLJDWLRQDOWUHDWPHQWVLVSURYLGHGEHORZ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
38
7DEOH
'HVFULSWLRQRI)OXWLFDVRQH)XURDWH9LODQWHURO,QKDODWLRQ3RZGHU'U\
3RZGHU,QKDOHUDQGFRPSDUDWLYHWUHDWPHQWV
&RPSRXQG
)RUPXODWLRQ
)OXWLFDVRQH
)XURDWH9LODQWHURO
)LUVW VWULS ))  PFJ RU  PFJ EOHQGHG ZLWK
ODFWRVH
6HFRQGVWULS9LODQWHUROPFJEOHQGHGZLWKODFWRVH
DQGPDJQHVLXPVWHDUDWH
'RVDJH)RUP
'3,(OOLSWD ± GRVHVSHUGHYLFH
8QLW'RVH6WUHQJWK
PFJPFJRUPFJPFJSHUDFWXDWLRQ
5RXWHRI$GPLQLVWUDWLRQ
,QKDOHG
&RPSRXQG
)RUPXODWLRQ
)OXWLFDVRQHSURSLRQDWH6DOPHWHURO
)3PFJRUPFJEOHQGHGZLWKODFWRVH
6DOPHWHUROPFJEOHQGHGZLWKODFWRVH
'RVDJH)RUP
'3,'LVNXV± GRVHVSHUGHYLFH
8QLW'RVH6WUHQJWK
PFJPFJRUPFJPFJSHUDFWXDWLRQ
5RXWHRI$GPLQLVWUDWLRQ
,QKDOHG
&RPSRXQG
)RUPXODWLRQ
%XGHVRQLGH)RUPRWHURO)XPDUDWH
%XGHVRQLGH  PFJ RU  PFJ  EOHQGHG ZLWK
ODFWRVH
)RUPRWHURO)XURDWHPFJRUPFJEOHQGHGZLWK
ODFWRVH
'RVDJH)RUP
'3,7XUEXKDOHU RUGRVHVPFJPFJRU
PFJPFJSHUGHYLFH
8QLW'RVH6WUHQJWK
PFJPFJRUPFJPFJSHUDFWXDWLRQ
5RXWHRI$GPLQLVWUDWLRQ
,QKDOHG

PDWJQHVLXPVWHDUDWH  ZZ RIWRWDOGUXJSURGXFW
7KHVXEMHFW¶VXVHRIVKRUWUDSLGDFWLQJEHWDDJRQLVWEURQFKRGLODWRUZLOOEHDVVHVVHGDVLW
ZRXOGEHLQURXWLQHFDUHDQGLIUHTXLUHGUHVFXHPHGLFDWLRQZLOOEHSUHVFULEHGWRVXEMHFWV
WRXVHDVQHHGHGWKURXJKRXWWKHVWXG\IRUUHOLHIRIDVWKPDV\PSWRPVDVSHUXVXDOSUDFWLFH

0HGLFDO'HYLFHV
0HGLFDOGHYLFHVVSLURPHWHUVZLOOEHSURYLGHGE\*6.IRUXVHLQWKLVVWXG\+RZHYHU
QRQHRIWKHGHYLFHVSURYLGHGDUHPDQXIDFWXUHGE\RURQEHKDOIRI*6.

7UHDWPHQW$VVLJQPHQW
6XEMHFWVZLOOEHDVVLJQHGWRVWXG\WUHDWPHQWLQDFFRUGDQFHZLWKWKHUDQGRPLVDWLRQ
VFKHGXOH
6XEMHFWVZLOOEHUDQGRPL]HGWRRQHRIWKHIROORZLQJWUHDWPHQWJURXSV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
39
!
))9,DVSHUGRVHJXLGDQFHEHORZ
!
,QLWLDWHRQXVXDOLQKDOHGGU\SRZGHU,&6/$%$IL[HGFRPELQDWLRQIRUDVWKPD
PDLQWHQDQFHWKHUDS\LH6HUHWLGH'LVNXV RU6\PELFRUW 7XUEXKDOHUDFFRUGLQJWR
XVXDOSK\VLFLDQ¶VSUHVFULSWLRQ
'RVH*XLGDQFH
)RUVXEMHFWVUDQGRPLVHGWR))9,,QYHVWLJDWRUFDQPDNHGRVLQJGHFLVLRQEDVHGRQWKH
JXLGDQFHEHORZ
!
))9,PFJPFJGRVH RQFHDGD\LVDSSUR[LPDWHO\HTXLYDOHQWWRIOXWLFDVRQH
SURSLRQDWHVDOPHWHURO)36PHGLXPGRVHPFJPFJDQGWR
EXGHVRQLGHIRUPRWHURO%8')PHGLXPGRVHPFJPFJWZLFHDGD\6HH
7DEOH IRUIXUWKHUJXLGDQFHIRUGRVHVFRQYHUVLRQIRURWKHUFRUWLFRVWHURLGV
!
))9,PFJPFJGRVHRQFHDGD\LVDSSUR[LPDWHO\HTXLYDOHQWWRIOXWLFDVRQH
SURSLRQDWHVDOPHWHUROKLJKGRVHPFJPFJDQGWREXGHVRQLGHIRUPRWHURO
KLJKGRVHPFJPFJWZLFHDGD\6HH7DEOH IRUJXLGDQFHIRUGRVH
FRQYHUVLRQIRURWKHUFRUWLFRVWHURLGV
!
6WDUWLQJ GRVHV DUH  PFJ PFJ RQFH GDLO\ IRU ))9,  PFJ PFJ WZLFH
GDLO\IRU)36DQGPFJPFJWZLFHGDLO\ IRU%8')
7DEOH
,&6/$%$'DLO\'RVH6P3&6HUHWLGH'LVNXV 6\PELFRUW
7XUEXKDOHU
)RUPXODWLRQ
,QKDOHU'HYLFHV
'RVHV$YDLODEOHPFJ
,&6/$%$DQG
,QKDODWLRQVGD\
)OXWLFDVRQH
SURSLRQDWHVDOPHWHURO
'3,'LVNXV
LQKDODWLRQ[
0HGLXPGRVH
+LJKGRVH
%XGHVRQLGHIRUPRWHURO
'3,7XUEXKDOHU
LQKDODWLRQV[
0HGLXPGRVH
+LJKGRVH
,QIRUPDWLRQH[WUDFWHGIURP*,1$ UHIHUWR*,1$IRUIXUWKHUJXLGDQFH
)RUSDWLHQWVZLWKPRGHUDWHWRVHYHUHKHSDWLFLPSDLUPHQWWKH PLFURJUDPVGRVH
VKRXOGEHXVHGDQGSDWLHQWVVKRXOGEHPRQLWRUHGIRUV\VWHPLFFRUWLFRVWHURLGUHODWHG
DGYHUVHUHDFWLRQVVHH6P3&

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
40

3ODQQHG'RVH$GMXVWPHQWV
6XEMHFWVUDQGRPLVHGWRWKHXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\DUPFDQKDYH
WKHLUWUHDWPHQWDGMXVWHGDVZRXOGEHQRUPDOFOLQLFDOSUDFWLFHDWWKH,QYHVWLJDWRU¶V
GLVFUHWLRQ7KLVZLOOQRWUHTXLUHWKHVXEMHFWWREHZLWKGUDZQIURPWKHVWXG\7KHVH
VXEMHFWVVKRXOGQRWUHFHLYH))9,LIWKHPHGLFDWLRQLVPDUNHWHGGXULQJWKHVWXG\SHULRG
6XEMHFWVUDQGRPL]HGWRWKH))9,DUPDQGIRUZKRPLWLVFRQVLGHUHGDSSURSULDWH
QHFHVVDU\WRDGMXVWWUHDWPHQWFDQKDYHWKHLUUHJLPHQFKDQJHGDVUHTXLUHGDVSHUQRUPDO
FOLQLFDOSUDFWLFHDWDQ\SRLQWLQWKHVWXG\DQGWKHVXEMHFWFRXOGUHPDLQLQWKHVWXG\
6XEMHFWVRQ))9,DUPFDQDOVRFKDQJHEHWZHHQWKHWZR))9,GRVHVDVDSSURSULDWHDQG
DWWKH,QYHVWLJDWRU¶VGLVFUHWLRQ

%OLQGLQJ
7KLVVWXG\LVDQRSHQODEHOUDQGRPLVHGVWXG\

3DFNDJLQJDQG /DEHOLQJ
7KHFRQWHQWVRIWKHODEHOZLOOEHLQDFFRUGDQFHZLWKDOODSSOLFDEOHUHJXODWRU\
UHTXLUHPHQWV

3UHSDUDWLRQ+DQGOLQJ6WRUDJH$FFRXQWDELOLW\
$OO))9,DQGFRPSDUDWLYH,&6/$%$PDLQWHQDQFHWKHUDS\SUHVFULEHGWKURXJKRXWWKH
VWXG\ZLOOEHGLVSHQVHGDWDQGFROOHFWHGIURPWKHLQYHVWLJDWRUVLWH
,QYHVWLJDWLRQDOSURGXFWPXVWEHVWRUHGLQDVHFXUHDUHDXQGHUWKHDSSURSULDWHSK\VLFDO
FRQGLWLRQVIRUWKHSURGXFW$OO'3,VFRQWDLQLQJ))9,PXVWEHVWRUHGDWDWHPSHUDWXUHRI
XSWR&%XGHVRQLGH)RUPRWHURO'3,VPXVWEHVWRUHGDWDWHPSHUDWXUHRIXSWR&
DQG)OXWLFDVRQH3URSLRQDWH6DOPHWHURO'3,VVWRUHGDW#&
$FFHVVWRDQGDGPLQLVWUDWLRQRIWKHLQYHVWLJDWLRQDOSURGXFWZLOOEHOLPLWHGWRWKH
LQYHVWLJDWRUDQGDXWKRULVHGVLWHVWDII,QYHVWLJDWLRQDOSURGXFWPXVWEHGLVSHQVHGRU
DGPLQLVWHUHGRQO\WRVXEMHFWVHQUROOHGLQWKHVWXG\DQGLQDFFRUGDQFHZLWKWKHSURWRFRO
$OOXVHGDQGXQXVHGVWXG\PHGLFDWLRQLQKDOHUV))9,RUXVXDO,&6/$%$DVWKPD
PDLQWHQDQFHWKHUDS\VKRXOGEHUHWXUQHGWRWKHLQYHVWLJDWRUVLWHZKHQWKHVXEMHFWVFROOHFW
SUHVFULSWLRQVRIVWXG\PHGLFDWLRQ
$WWKHHQGRIWKHVWXG\DOOVWXG\VXSSOLHGVWXG\PHGLFDWLRQXVHGDQGXQXVHGZLOOEH
GHVWUR\HGIROORZLQJORFDOVWDQGDUGRSHUDWLQJSURFHGXUHVH[FHSWZKHUHLWLVVXVSHFWHGWKDW
(OOLSWD RU*6.'3,SDFNDJLQJLVGHIHFWLYH7KHGHYLFHDQGSDFNDJLQJVKRXOGEH
UHWXUQHGWR*6.
'HWDLOVIRUERWKUHWXUQDQGGHVWUXFWLRQDQGRIVWXG\PHGLFDWLRQDUHIRXQGLQWKH6WXG\
3URFHGXUH0DQXDO630

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
41
8QGHUQRUPDOFRQGLWLRQVRIKDQGOLQJDQGDGPLQLVWUDWLRQLQYHVWLJDWLRQDOSURGXFWLVQRW
H[SHFWHGWRSRVHVLJQLILFDQWVDIHW\ULVNVWRVLWHVWDII7DNHDGHTXDWHSUHFDXWLRQVWRDYRLG
GLUHFWH\HRUVNLQFRQWDFWDQGWKHJHQHUDWLRQRIDHURVROVRUPLVWV1RWLI\WKHPRQLWRURI
DQ\XQLQWHQWLRQDORFFXSDWLRQDOH[SRVXUH$0DWHULDO6DIHW\'DWD6KHHW06'6
GHVFULELQJWKHRFFXSDWLRQDOKD]DUGVDQGUHFRPPHQGHGKDQGOLQJSUHFDXWLRQVZLOOEH
SURYLGHGWRVLWHVWDIILIUHTXLUHGE\ORFDOODZVRUZLOORWKHUZLVHEHDYDLODEOHIURP*6.
XSRQUHTXHVW
,QDFFRUGDQFHZLWKORFDOUHJXODWRU\UHTXLUHPHQWVWKH,QYHVWLJDWRUGHVLJQDWHGVLWHVWDII
RUKHDGRIWKHPHGLFDOLQVWLWXWLRQZKHUHDSSOLFDEOHPXVWGRFXPHQWWKHDPRXQWRI
LQYHVWLJDWLRQDOSURGXFWGLVSHQVHGDQGRUDGPLQLVWHUHGWRVWXG\VXEMHFWVWKHDPRXQW
UHWXUQHGE\VWXG\VXEMHFWVDQGWKHDPRXQWUHFHLYHGIURPDQGUHWXUQHGWR*6.ZKHQ
DSSOLFDEOH3URGXFWDFFRXQWDELOLW\UHFRUGVPXVWEHPDLQWDLQHGWKURXJKRXWWKHFRXUVHRI
WKHVWXG\

,QYHVWLJDWLRQDO3URGXFW0DOIXQFWLRQ
$Q\LQYHVWLJDWLRQDOSURGXFWLQKDOHUWKDWIDLOVWRIXQFWLRQSURSHUO\PXVWEHLGHQWLILHGWR
*6.SHUVRQQHO'HWDLOVRIWKHIDLOXUHZLOOEHGRFXPHQWHGLQWKHH&5)(OOLSWDLQKDOHUV
ZLOOEHUHWXUQHGWR*6.IRUWHVWLQJ7KHVXEMHFWVKRXOGUHWXUQWKHLQKDOHUWRWKHFOLQLFDV
VRRQDVSRVVLEOHWRDYRLGPLVVLQJDQ\GRVHV7KHVLWHZLOOWKHQFRQWDFW*6.¶VLQWHUQDO
,:56DOVRNQRZQDVWKH5HJLVWUDWLRQDQG0HGLFDWLRQ2UGHULQJ6\VWHP>5$026@1*
DQGREWDLQDQHZWUHDWPHQWSDFNQXPEHUIRUWKLVVXEMHFWDQGGLVSHQVHDQHZVWXG\
PHGLFDWLRQNLWIURPWKHVLWH
VLQYHVWLJDWLRQDOSURGXFWVXSSO\DVLQVWUXFWHGSHUWKH,:56

&RPSOLDQFHZLWK6WXG\7UHDWPHQW$GPLQLVWUDWLRQ
:KHQWKHVXEMHFWVDWWHQGWKHLQYHVWLJDWRUVLWHWKH\ZLOOEHLQVWUXFWHGWRDGPLQLVWHUWKH
VWXG\PHGLFDWLRQRQFHGDLO\DWWKHVDPHWLPHRIWKHGD\IRUWKHGXUDWLRQRIWKHWUHDWPHQW
ZKHQUDQGRPLVHGWR))9,YLD(OOLSWD70 DQGWZLFHGDLO\RQWKHPRUQLQJDQGHYHQLQJ
ZKHQUDQGRPLVHGWR,&6/$%$'3,'LVNXV70 RU7XUEXKDOHU$OOXVHGDQGXQXVHG
VWXG\PHGLFDWLRQLQKDOHUV))9,RUXVXDODVWKPDPDLQWHQDQFHWKHUDS\VKRXOGEH
UHWXUQHGWRWKHLQYHVWLJDWRUVLWHZKHQWKHVXEMHFWVFROOHFWSUHVFULSWLRQVRIVWXG\
PHGLFDWLRQ
7UHDWPHQWDGKHUHQFHZLWKVWXG\PHGLFDWLRQZLOOEHDVVHVVHGEDVHGRQDQDO\VLVRI
PHGLFDWLRQVGLVSHQVHGDQGFROOHFWHGGXULQJWKHVWXG\DQGRQ0HGLFDWLRQ$GKHUHQFH
5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDWUDQGRPLVDWLRQ'D\DW:HHN
DQGDW:HHN

7UHDWPHQWRI6WXG\7UHDWPHQW2YHUGRVH
$QRYHUGRVHZLOOEHGHILQHGDVWKHVXEMHFWUHFHLYLQJDQ\DPRXQWRI,3JUHDWHUWKDQWKH
PD[LPXPGRVHSHUPLWWHGE\WKHSURWRFROZKLFKUHVXOWVLQFOLQLFDOVLJQVRUV\PSWRPV
,QWKHHYHQWRIDQRYHUGRVHRIVWXG\PHGLFDWLRQWKH,QYHVWLJDWRUVKRXOGXVHFOLQLFDO
MXGJPHQWLQWUHDWLQJWKHRYHUGRVHDQGFRQWDFWWKHVWXG\PHGLFDOPRQLWRU

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
42
*OD[R6PLWK.OLQH*6.LVQRWUHFRPPHQGLQJVSHFLILFWUHDWPHQWJXLGHOLQHVIRURYHUGRVH
DQGWR[LFLW\PDQDJHPHQW7KH,QYHVWLJDWRUVKRXOGUHIHUWRWKHUHOHYDQWGRFXPHQWVIRU
GHWDLOHGLQIRUPDWLRQUHJDUGLQJZDUQLQJVSUHFDXWLRQVFRQWUDLQGLFDWLRQVDGYHUVHHYHQWV
DQGRWKHUVLJQLILFDQWGDWDSHUWDLQLQJWRWKHVWXG\GUXJEHLQJXVHGLQWKLVVWXG\6XFK
GRFXPHQWVPD\LQFOXGHEXWQRWEHOLPLWHGWRWKH,%VRUHTXLYDOHQWGRFXPHQWSURYLGHG
E\*6.IRUVWXG\PHGLFDWLRQV

7UHDWPHQWDIWHUWKH(QGRIWKH6WXG\
7KHLQYHVWLJDWRULVUHVSRQVLEOHIRUHQVXULQJWKDWFRQVLGHUDWLRQKDVEHHQJLYHQWRWKHSRVW
VWXG\FDUHRIWKHSDWLHQW¶VPHGLFDOFRQGLWLRQZKHWKHURUQRW*6.LVSURYLGLQJVSHFLILF
SRVWVWXG\WUHDWPHQW

&RQFRPLWDQW0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
$OOUHVSLUDWRU\UHODWHGSUHVFULEHGDQGGLVSHQVHGFRQFRPLWDQWPHGLFDWLRQVWDNHQGXULQJ
WKHVWXG\ZLOOEHUHFRUGHG7KHPLQLPXPUHTXLUHPHQWLVWKDWGUXJWUDGHQDPHDQGWKH
GDWHVRISUHVFULELQJGLVSHQVLQJDQGFROOHFWLRQZLOOEHUHFRUGHG

3HUPLWWHG0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
$OOPHGLFDWLRQVIRUDVWKPDDQGRWKHUGLVRUGHUVWKDWDUHQRWFRQWUDLQGLFDWHGLQDVWKPDRU
OLVWHGDVDSURKLELWHGPHGLFDWLRQVHH6HFWLRQPD\EHFRQWLQXHGWKURXJKRXWWKH
VWXG\
$WFOLQLFDOGRVHVORZSODVPDFRQFHQWUDWLRQVRI))DQG9,DUHDFKLHYHGDIWHULQKDOHG
GRVLQJGXHWRH[WHQVLYHILUVWSDVVPHWDEROLVPDQGKLJKV\VWHPLFFOHDUDQFHPHGLDWHGE\
F\WRFKURPH3$LQWKHJXWDQGRUOLYHUDQ\FOLQLFDOO\VLJQLILFDQWGUXJLQWHUDFWLRQV
PHGLDWHGE\))RU9,DUHXQOLNHO\
$&<3$GUXJLQWHUDFWLRQVWXG\ZDVSHUIRUPHGLQKHDOWK\VXEMHFWVZLWKWKH))9,
FRPELQDWLRQDQG.HWRFRQD]ROH&RDGPLQLVWUDWLRQLQFUHDVHGPHDQ))$8&
DQG&PD[E\DQGUHVSHFWLYHO\7KHLQFUHDVHLQ))H[SRVXUHZDV
DVVRFLDWHGZLWKDUHGXFWLRQLQKZHLJKWHGPHDQVHUXPFRUWLVRO &R
DGPLQLVWUDWLRQLQFUHDVHGPHDQ9,$8&W¶DQG&PD[DQGUHVSHFWLYHO\7KH
LQFUHDVHLQ9,H[SRVXUHZDVQRWDVVRFLDWHGZLWKDQLQFUHDVHLQEHWDDJRQLVWUHODWHG
V\VWHPLFHIIHFWVRQKHDUWUDWHEORRGSRWDVVLXPRU47F)LQWHUYDO
&DUHLVDGYLVHGZKHQFRDGPLQLVWHULQJSRWHQWF\WRFKURPH3$LQKLELWRUVHJ
NHWRFRQD]ROHULWRQDYLUDVWKHUHLVSRWHQWLDOIRUDQLQFUHDVHGV\VWHPLFH[SRVXUHWRERWK
))DQG9,&RQVLGHUDWLRQVKRXOGEHJLYHQWRWKHFOLQLFDOVLWXDWLRQDQGWKHGXUDWLRQRI
WUHDWPHQWZLWKVXFKFRQFXUUHQWPHGLFDWLRQV

3URKLELWHG0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
!
6\VWHPLFFRUWLFRVWHURLGVH[FHSWLQFDVHRIDVHYHUHDVWKPDH[DFHUEDWLRQ
!
0RQRFORQDODQWLERG\RPDOL]XPDE;RODLU

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
43

678'<$66(660(176$1'352&('85(6
7KH7LPHDQG(YHQWV7DEOHLVSURYLGHGLQ6HFWLRQ$OOVWXG\DVVHVVPHQWVVKRXOGEH
FRQGXFWHGE\WKH,QYHVWLJDWRURUKLVKHUTXDOLILHGGHVLJQHHXQOHVVRWKHUZLVHVSHFLILHGLQ
WKHSURWRFRORU6303OHDVHUHIHUWRWKH630IRUWKHVXJJHVWHGRUGHU RIDVVHVVPHQWV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
44

7LPHDQG(YHQWV7DEOH
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone call 1
Visit 4**
Visit 5
Phone call 2
Visit 6
Early Withdrawal
Study week (± specified no. of days)
'D\WR
'D\
:HHN  
GD\V
:HHN
GD\V
:HHN  
GD\V
:HHN
GD\V
Early Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
Assessments
,QIRUPHG&RQVHQW
x
(OLJLELOLW\FULWHULD
x
x
'HPRJUDSK\
x
6PRNLQJVWDWXV
x
0HGLFDO)DPLO\ KLVWRU\ RI FRQVHQWHG VXEMHFWV
LQFOXGLQJ &9 5LVN IDFWRUV DQG H[DFHUEDWLRQ
KLVWRU\
x
3*[VDOLYDVDPSOH
x
3K\VLFDOH[DPLQDWLRQ
x
x
x
x
x
Safety Assessments
8ULQH3UHJQDQF\7HVW
x
x
x
x
([DFHUEDWLRQ$VVHVVPHQW
x
x
x
x
x
x
9LWDOVLJQV
x
x
x
x
x
6HULRXV $GYHUVH (YHQW DQG $GYHUVH 'UXJ
5HDFWLRQ$VVHVVPHQW
x
x
x
x
x
x
Efficacy Assessments
6SLURPHWU\7HVWLQJ3UHGRVHWURXJK)(9
x
x
x 
Subject Questionnaires 
$VWKPD&RQWURO7HVW
x
x
x
x
x
x
x
(4'
x
x
x
$VWKPD4XDOLW\RI
/LIH4XHVWLRQQDLUH
x
x
x
0$56$TXHVWLRQQDLUH
x
x
x
x



2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
45
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone call 1
Visit 4**
Visit 5
Phone call 2
Visit 6
Early Withdrawal
Study week (± specified no. of days)
'D\WR
'D\
:HHN  
GD\V
:HHN
GD\V
:HHN  
GD\V
:HHN
GD\V
Early Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH3$6$34
x
x
Inhaler correct use assessment
&ULWLFDODQGQRQFULWLFDO HUURUVUHFRUG
x
x
x
Medication Assessments
&RQFRPLWDQW0HGLFDWLRQ$VVHVVPHQW
x
x
x
x
x
'LVSHQVH6WXG\0HGLFDWLRQð
x
x
&ROOHFW6WXG\0HGLFDWLRQð
x
x
x
RAMOS/eCRF
5$0261*
x
x
H&5)
x
x
x
x
x
x
x

6$(DQG$'5PRQLWRULQJZLOORFFXUIURP'D\6$(UHODWHG WRVWXG\SDUWLFLSDWLRQVKRXOGEHJLQIURPVLJQLQJRI,&)$QDGGLWLRQDOVDIHW\DQG$&7FKHFNLVSURYLGHGE\SKRQHDW
ZHHNDQG

7KURXJKRXWWKHVWXG\WKHVWXG\PHGLFDWLRQZLOOEHGLVSHQVHGDQGFROOHFWHGE\WKHLQYHVWLJDWRUVLWH
9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLVXVXDODVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH7KHQWKLVYLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEH
FROOHFWHGDWWKLVYLVLW:ULWWHQ,QIRUPHG&RQVHQWPXVWEHREWDLQHGSULRUWRLQLWLDWLRQRIVWXG\SURFHGXUHVRULQLWLDWLQJFKDQJHVLQPHGLFDWLRQV
 9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW 5DQGRPLVDWLRQYLVLW
3*[VDOLYDVDPSOHFROOHFWHGDW9LVLW5DQGRPLVDWLRQRUDQ\VFKHGXOHGFOLQLFYLVLWWKHUHDIWHU
 2QO\LIHDUO\ZLWKGUDZDORFFXUVEHIRUH:HHN
2QO\IRUFKLOGEHDULQJZRPHQ
1RWH$OODGYHUVHHYHQWVZLOOEHUHFRUGHGLQWKHVRXUFHGRFXPHQWVEXWRQO\LQIRUPDWLRQUHJDUGLQJQRQVHULRXVDGYHUVHGUXJUHDFWLRQV$'5VDQGVHULRXVDGYHUVHHYHQWV6$(VZLOO
EHGRFXPHQWHGDQGUHSRUWHGLQWKHH&5)



2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
46

6FUHHQLQJDQG&ULWLFDO%DVHOLQH$VVHVVPHQWV
7KHIROORZLQJGHPRJUDSKLFSDUDPHWHUVZLOOEHFDSWXUHG\HDURIELUWKVH[DQGHWKQLFLW\
0HGLFDOPHGLFDWLRQIDPLO\KLVWRU\ZLOOEHDVVHVVHGDVUHODWHGWRWKHLQFOXVLRQH[FOXVLRQ
FULWHULDOLVWHGLQ6HFWLRQ DQGDVLQGLFDWHGLQWKHWLPHDQGHYHQWWDEOH
&DUGLRYDVFXODUPHGLFDOKLVWRU\&9ULVNIDFWRUVDQGH[DFHUEDWLRQKLVWRU\ZLOOEHDVVHVVHG
DVLQGLFDWHGLQWKHWLPHDQGHYHQWWDEOH
6PRNLQJVWDWXVZLOOEHDOVRFDSWXUHGDVIROORZVQRQVPRNHUFXUUHQWRUIRUPHUFLJDUHWWH
VPRNHUV)RUPHUVPRNHUVZLOOEHGHILQHGDVWKRVHZKRKDYHVWRSSHGVPRNLQJIRUDWOHDVW
PRQWKVSULRUWR9LVLWRU9LVLWLIWKHYLVLWDQGDUHFRPELQHG1XPEHURISDFN
\HDUVVKRXOGEHDVVHVVHG DWVFUHHQLQJ9LVLWQXPEHURISDFN\HDUV QXPEHURI
FLJDUHWWHVSHUGD\[QXPEHURI\HDUVVPRNHGHJFLJDUHWWHVSHUGD\IRU
\HDUVRUFLJDUHWWHVSHUGD\IRU\HDUV
3URFHGXUHVFRQGXFWHGDVSDUWRIWKHVXEMHFW¶VURXWLQHFOLQLFDOPDQDJHPHQW>HJEORRG
FRXQW@DQGREWDLQHGSULRUWRVLJQLQJRILQIRUPHGFRQVHQWPD\EHXWLOL]HGIRU6FUHHQLQJRU
EDVHOLQHSXUSRVHVSURYLGHGWKHSURFHGXUHPHHWVWKHSURWRFROGHILQHGFULWHULDDQGKDV
EHHQSHUIRUPHGLQWKHWLPHIUDPHRIWKHVWXG\
$&7ZLOOEHDVVHVVHGDWVFUHHQLQJ9LVLWDQGUDQGRPLVDWLRQ9LVLW$4/46(4
'DQG0$56$ZLOOEHDVVHVVHGDW9LVLW5DQGRPLVDWLRQ7KHVH3DWLHQW5HSRUWHG
2XWFRPHVTXHVWLRQQDLUHVVKRXOGEHFRPSOHWHGE\VXEMHFWVEHIRUH DQ\RWKHUDVVHVVPHQWDW
DFOLQLFYLVLWLQWKHRUGHUVSHFLILHG7KHFRUUHFWXVHRILQKDOHUZLOOEHDVVHVVHGDOVRDW
UDQGRPL]DWLRQYLVLW9LVLW
 DIWHUUHDGLQJWKHSDFNDJHLQVHUWRISURGXFWE\WKHSDWLHQWDQG
 DIWHUGHPRQVWUDWLRQRILWXVHE\WKHLQYHVWLJDWRU$Q\FULWLFDOHUURUVZLOOEHUHJLVWHUHG
E\WKH,QYHVWLJDWRUZKHQXVLQJHDFKGHYLFH
%DVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\WKH,QYHVWLJDWRUXVLQJD
VSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHGKRXUV
EHIRUHEDVHOLQHVSLURPHWU\DQGXVXDODVWKPDPHGLFDWLRQZLOOEHQRWEHWDNHQE\WKH
SDWLHQWEHIRUHFRPLQJRQVLWH
1RVWXG\UHODWHGSURFHGXUHVPD\EHSHUIRUPHGXQWLOWKHLQIRUPHGFRQVHQWIRUP
GRFXPHQWKDVEHHQUHYLHZHGZLWKDQGVLJQHGE\WKHVXEMHFW

(IILFDF\
6HH6HFWLRQ IRUWKHHIILFDF\HQGSRLQWVDQG6HFWLRQ IRUWKHSURSRVHGWLPHDQGHYHQWV
WDEOH

,QKDOHU&RUUHFW8VH$VVHVVPHQW
&RUUHFWXVHRIWKHLQKDOHUZLOOEHDVVHVVHGDVRXWOLQHGLQWKH7LPHDQG(YHQWV7DEOH
6HFWLRQ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
47
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUV IRU(OOLSWDTM
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURU
LVGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJ
LQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@ 1R
>@<HV LI\HVWLFNDSSURSULDWH RSWLRQVEHORZ
&ULWLFDO (UURUV IRU(OOLSWD70
\HV
QR
1RQFULWLFDO
(UURUV
IRU
(OOLSWD70
\HV
QR
)DLOHGWRRSHQFRYHU
1R
H[KDODWLRQ
EHIRUH
DQ
LQKDODWLRQ
6KRRN WKH GHYLFH XSVLGH GRZQ
DIWHUGRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUH ZDV
QRW

ORQJ

VWHDG\

GHHS
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH

1R VHDO E\ WKH OLSV DURXQG WKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWKROGEUHDWK
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFW WKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
48
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUV IRU'LVNXVTM
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURU
LVGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDO PHGLFDWLRQEHLQJ
LQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@ 1R
>@<HV LI\HVWLFNDSSURSULDWH RSWLRQVEHORZ
&ULWLFDO(UURUV IRU'LVNXV70
\HV
QR
1RQFULWLFDO(UURUV IRU
'LVNXV70
\HV
QR
)DLOHGWRRSHQFRYHU
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
/HYHULVQRWSXVKHGEDFN
,QKDODWLRQPDQRHXYUH ZDV
QRW

VWHDG\

GHHS
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
'LGQRWKROGEUHDWK
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
49
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUV IRU7XUEXKDOHU
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURU
LVGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDO PHGLFDWLRQEHLQJ
LQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@ 1R
>@<HV LI\HVWLFNDSSURSULDWH RSWLRQVEHORZ
&ULWLFDO(UURUV IRU7XUEXKDOHU
\HV
QR
1RQFULWLFDO(UURUV IRU
7XUEXKDOHU
\HV
QR
)DLOHGWRUHPRYHFDS
'HYLFH WLSSHGGRZQZDUGV
DIWHUGRVHSUHSDUDWLRQ
'LGQRWKROGGHYLFHXSULJKW
2.GXULQJGRVHSUHSDUDWLRQ
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
%DVHQRWWZLVWHGIXOO\EDFNZDUGV
DQGIRUZDUGVQRFOLFNKHDUG
,QKDODWLRQPDQRHXYUH ZDV
QRW

IRUFHIXO

GHHS
1RWHWR+&3 LWLVLPSRUWDQW
WKDWWKHLQKDODWLRQLVIRUFHIXO
DQGGHHSIURPWKHVWDUWIRU
WKLVLQKDOHU
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWKROGEUHDWK
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@

7URXJKSUHGRVH)(9DVVHVVPHQW
)(9 ZLOOEHPHDVXUHGWRDVVHVVOXQJIXQFWLRQDW9LVLW5DQGRPLVDWLRQDQG9LVLW
:HHNDVRXWOLQHGLQWKH7LPHDQG(YHQWV7DEOH9LVLW:HHNVKRXOGEH
VFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQYLVLW0HDVXUHPHQWVVKRXOG
EHWDNHQ SUHGRVHDQGVXEMHFWVVKRXOGEHLQVWUXFWHGQRWWRWDNHWKHLUDVWKPD
PHGLFDWLRQVWXG\GUXJSULRUWRFRPLQJLQWRWKHFOLQLFDWWKHVHYLVLWV6XEMHFWVVKRXOGDOVR

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
50
ZLWKKROGIURPXVLQJWKHLUUHVFXHPHGLFDWLRQIRUDWOHDVWKRXUVSULRUWR9LVLW
5DQGRPLVDWLRQDQG9LVLW:HHN
$OOVLWHVZLOOXVHVWDQGDUGLVHGVSLURPHWU\HTXLSPHQWSURYLGHGE\*6.)RUHDFK
REVHUYDWLRQDWOHDVWZLWKQRPRUHWKDQHIIRUWVZLOOEHREWDLQHG$WOHDVWWZRRIWKH
VSLURPHWU\HIIRUWVVKRXOGEHDFFHSWDEOHDQGUHSHDWDEOH7KH EHVW)(9YDOXHZLOOEH
UHFRUGHGLQWKHH&5)
7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRSHUIRUPWKHVSLURPHWU\DWWKHVDPH
WLPHRIWKHGD\DW9LVLWDQGDW9LVLW

4XHVWLRQQDLUHV

$VWKPD&RQWURO7HVW$&7
7KH$&7LVDYDOLGDWHGVHOIDGPLQLVWHUHGTXHVWLRQQDLUHXWLOLVLQJTXHVWLRQVWRDVVHVV
DVWKPDFRQWUROGXULQJWKHSDVWZHHNVRQDSRLQWFDWHJRULFDOVFDOHWR6XEMHFWV
ZLOOFRPSOHWHWKH$&7DW6FUHHQLQJ9LVLWDW5DQGRPLVDWLRQ9LVLWDW:HHN
3KRQH&DOORU9LVLWDW:HHN9LVLWDW:HHN3KRQH&DOORU9LVLWDQG
DW:HHN9LVLW (DUO\:LWKGUDZDOYLVLW
$Q$&7VFRUHRIWRVXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLVXQOLNHO\WREHZHOO
FRQWUROOHG$VFRUHRIWRVXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLVOLNHO\WREHZHOO
FRQWUROOHG
3OHDVHUHIHUWR$SSHQGL[ DQGWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV

$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH$4/46
7KH$4/4LVDGLVHDVHVSHFLILFVHOIDGPLQLVWHUHGTXDOLW\RIOLIHTXHVWLRQQDLUHGHYHORSHG
WRHYDOXDWHWKHLPSDFWRIDVWKPDWUHDWPHQWVRQWKHTXDOLW\RIOLIHRIDVWKPDVXIIHUHUVRYHU
WKHODVWZHHNV>-XQLSHU @$4/46ZLOOEHPHDVXUHGDW5DQGRPLVDWLRQ9LVLW
DW:HHN9LVLW(DUO\:LWKGUDZDOYLVLW 3OHDVHUHIHUWR$SSHQGL[ DQGWKH6WXG\
3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV

(XUR4RO4XHVWLRQQDLUH(4'/HYHO
*HQHUDOKHDOWKVWDWXVZLOOEHDVVHVVHGZLWKWKH(XUR4RO(4'/HYHO4XHVWLRQQDLUH
DW5DQGRPLVDWLRQ9LVLWDQGDW:HHN9LVLW(DUO\:LWKGUDZDOYLVLW
3OHDVHUHIHUWR$SSHQGL[ DQGWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV

0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$
5HSRUWHGDGKHUHQFHWRPHGLFDWLRQZLOOEHDVVHVVHGZLWKWKH0HGLFDWLRQ$GKHUHQFH
5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDW9LVLW:HHN9LVLWDQG
:HHN9LVLW(DUO\:LWKGUDZDOYLVLW
7KH0$56$LVDLWHPTXHVWLRQQDLUHZKHUHPHGLFDWLRQXVHLVUDWHGRQDSRLQW
/LNHUWVFDOHLQGLFDWLQJµDOZD\V¶WRLQGLFDWLQJµQHYHU¶,WKDVEHHQYDOLGDWHGDVDVHOI

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
51
UHSRUWHGPHDVXUHRIDGKHUHQFHZLWK,&6IRUVXEMHFWVZLWKDVWKPDDQGLQFOXGHVJHQHULF³,
XVHLWUHJXODUO\HYHU\GD\´DQGOXQJFRQGLWLRQVSHFLILFTXHVWLRQVDERXWPHGLFDWLRQXVH
³,RQO\XVHLWZKHQ,IHHOEUHDWKOHVV´>&RKHQ@7KHUHLVQRVSHFLILHGWLPHIUDPHRQ
ZKLFKUHVSRQVHVVKRXOGEHEDVHG
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH0$56$DWWKHVDPHWLPHDW
WKHVSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH0$56$KDYHQRVSHFLILHG
WLPHIUDPHRQZKLFKUHVSRQVHVVKRXOGEHEDVHG

3DWLHQWV6DWLVIDFWLRQDQG3UHIHUHQFHZLWKWKHGHYLFH3$6$3
4XHVWLRQQDLUH
7KH3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH3$6$34>&0.R]PD@
LVDPXOWLLWHPPHDVXUHRIUHVSLUDWRU\LQKDODWLRQGHYLFHVDWLVIDFWLRQDQGSUHIHUHQFH
GHVLJQHGWREHHDVLO\XQGHUVWRRGDQGDGPLQLVWHUHGWRSDWLHQWVZLWKDVWKPDDQG&23'
3DWLHQWVDWLVIDFWLRQZLWKHDFKGHYLFHDQGGHYLFHSUHIHUHQFHZLOOEHDVVHVVHGDW:HHN
9LVLW(DUO\:LWKGUDZDOYLVLWLIVXEMHFWLVZLWKGUDZQEHIRUH:HHN9LVLW
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH3$6$34DWWKHVDPHWLPHDW
WKHVSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH3$6$34KDVQRVSHFLILHG
WLPHIUDPHRQZKLFKUHVSRQVHVVKRXOGEHEDVHG

6DIHW\
3ODQQHGWLPHSRLQWVIRUDOOVDIHW\DVVHVVPHQWVDUHOLVWHGLQWKH7LPHDQG(YHQWV7DEOH
VHH6HFWLRQ
6HULRXV$GYHUVH(YHQWV6$(DQGQRQVHULRXV$GYHUVH'UXJ5HDFWLRQV$'5 ZLOOEH
FROOHFWHGLQWKLVVWXG\
6DIHW\HQGSRLQWVZLOOLQFOXGH
! )UHTXHQF\DQGW\SHRIVHULRXVDGYHUVHHYHQWV
! )UHTXHQF\DQGW\SHRIQRQVHULRXVDGYHUVHGUXJUHDFWLRQVUHODWHGWRWUHDWPHQW

$GYHUVH(YHQWV$($GYHUVH'UXJ5HDFWLRQV$'5VDQG
6HULRXV$GYHUVH(YHQWV6$(V
7KHGHILQLWLRQVRIDQ$($'5RU6$(FDQEHIRXQGLQ$SSHQGL[
7KHLQYHVWLJDWRUDQGWKHLUGHVLJQHHVDUHUHVSRQVLEOHIRUGHWHFWLQJGRFXPHQWLQJDQG
UHSRUWLQJHYHQWVWKDWPHHWWKHGHILQLWLRQRIDQ$(RU6$($OODGYHUVHHYHQWVZLOOEH
UHFRUGHGLQWKHVRXUFHGRFXPHQWVEXWRQO\LQIRUPDWLRQUHJDUGLQJQRQVHULRXVDGYHUVH
GUXJUHDFWLRQV$'5VDQGVHULRXVDGYHUVHHYHQWV6$(VZLOOEHGRFXPHQWHGDQG
UHSRUWHGLQWKHH&5)

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
52

7LPHSHULRGDQG)UHTXHQF\IRUFROOHFWLQJQRQVHULRXV$'5VDQG6$(
LQIRUPDWLRQ
!
$OOQRQVHULRXV$'5VDQG6$(VZLOOEHFROOHFWHGIURPWKHVWDUWRI6WXG\7UHDWPHQW
XQWLOWKHHQGRIWKHVWXG\VHH6HFWLRQDWWKHWLPHSRLQWVVSHFLILHGLQWKH
7LPHDQG(YHQWV7DEOH6HFWLRQ
!
0HGLFDORFFXUUHQFHVWKDWEHJLQSULRUWRWKHVWDUWRIVWXG\WUHDWPHQWEXWDIWHU
REWDLQLQJLQIRUPHGFRQVHQWPD\EHUHFRUGHGRQWKH0HGLFDO+LVWRU\&XUUHQW
0HGLFDO&RQGLWLRQVVHFWLRQRIWKH&5)
!
$Q\6$(VDVVHVVHGDVUHODWHGWRVWXG\SDUWLFLSDWLRQHJSURWRFROPDQGDWHG
SURFHGXUHVLQYDVLYHWHVWVRUFKDQJHLQH[LVWLQJWKHUDS\RUUHODWHGWRD*6.SURGXFW
ZLOOEHUHFRUGHGIURPWKHWLPHDVXEMHFWFRQVHQWVWRSDUWLFLSDWHLQWKHVWXG\XSWRDQG
LQFOXGLQJDQ\IROORZXSFRQWDFW
!
$OO6$(VZLOOEHUHFRUGHGDQGUHSRUWHGWR*6.ZLWKLQKRXUVDVLQGLFDWHGLQ
$SSHQGL[
!
,QYHVWLJDWRUVDUHQRWREOLJDWHGWRDFWLYHO\VHHN$(VRU6$(VLQIRUPHUVWXG\
VXEMHFWV+RZHYHULIWKHLQYHVWLJDWRUOHDUQVRIDQ\6$(LQFOXGLQJDGHDWKDWDQ\
WLPHDIWHUDVXEMHFWKDVEHHQGLVFKDUJHGIURPWKHVWXG\DQGKHVKHFRQVLGHUVWKH
HYHQWUHDVRQDEO\UHODWHGWRWKHVWXG\WUHDWPHQWRUVWXG\SDUWLFLSDWLRQWKHLQYHVWLJDWRU
PXVWSURPSWO\QRWLI\*6.
127(7KHPHWKRGRIUHFRUGLQJHYDOXDWLQJDQGDVVHVVLQJFDXVDOLW\RI$(VDQG6$(V
SOXVSURFHGXUHVIRUFRPSOHWLQJDQGWUDQVPLWWLQJ6$(UHSRUWVWR*6.DUHSURYLGHGLQ
$SSHQGL[

0HWKRGRI'HWHFWLQJQRQVHULRXV$'5VDQG6$(V
7KH,QYHVWLJDWRURUVLWHVWDIIZLOOEHUHVSRQVLEOHIRUGHWHFWLQJGRFXPHQWLQJ DQGUHSRUWLQJ
HYHQWVWKDWPHHWWKHGHILQLWLRQRIDQRQVHULRXVDGYHUVHGUXJUHDFWLRQ$'5RUVHULRXV
DGYHUVHHYHQWV6$(
7KHPHWKRGRIGHWHFWLQJUHFRUGLQJHYDOXDWLQJDQGIROORZXSRI6$(VDQGQRQVHULRXV
$'5VSOXVSURFHGXUHVIRUFRPSOHWLQJDQGWUDQVPLWWLQJ6$(UHSRUWVWR*6.DUHSURYLGHG
LQWKH6303URFHGXUHVIRUSRVWVWXG\6$(VQRQVHULRXV$'5VDUHSURYLGHGLQWKH630
&DUHZLOOEHWDNHQQRWWRLQWURGXFHELDVZKHQGHWHFWLQJ$(VDQGRU6$(V2SHQHQGHG
DQGQRQOHDGLQJYHUEDOTXHVWLRQLQJRIWKHVXEMHFWLVWKHSUHIHUUHGPHWKRGWRLQTXLUHDERXW
$(RFFXUUHQFH$SSURSULDWHTXHVWLRQVLQFOXGH
!
³+RZDUH\RXIHHOLQJ"´³+DYH\RXKDGDQ\RWKHUPHGLFDOSUREOHPVVLQFH\RXU
ODVWYLVLWFRQWDFW"´³+DYH\RXWDNHQDQ\QHZPHGLFLQHVRWKHUWKDQWKRVHSURYLGHG
LQWKLV VWXG\VLQFH\RXUODVWYLVLWFRQWDFW"´
3RWHQWLDO6$(VDQGQRQVHULRXV$'5VPD\EHLGHQWLILHGE\KRVSLWDOLVDWLRQDOHUWVWKURXJK
WKHPHGLFDOUHFRUG7KH,QYHVWLJDWRUZLOOKDYHWKHXOWLPDWHUHVSRQVLELOLW\IRUGHWHUPLQLQJ
FDXVDOLW\DQGVHULRXVQHVV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
53

)ROORZXS RIQRQVHULRXV$'5VDQG6$(V
$IWHUWKHLQLWLDOQRQVHULRXV$'5V6$(UHSRUWWKHLQYHVWLJDWRULVUHTXLUHGWRSURDFWLYHO\
IROORZHDFKVXEMHFWDWVXEVHTXHQWYLVLWVFRQWDFWV$OO6$(VDQGQRQVHULRXV$'5VZLOO
EHIROORZHGXQWLOUHVROXWLRQXQWLOWKHFRQGLWLRQVWDELOL]HVXQWLOWKHHYHQWLVRWKHUZLVH
H[SODLQHGRUXQWLOWKHVXEMHFWLVORVWWRIROORZXSDVGHILQHGLQ6HFWLRQ)XUWKHU
LQIRUPDWLRQRQIROORZXSSURFHGXUHVLVJLYHQLQ$SSHQGL[

&DUGLRYDVFXODUDQG'HDWK(YHQWV
)RUDQ\FDUGLRYDVFXODUHYHQWVGHWDLOHGLQ$SSHQGL[ DQGDOOGHDWKVZKHWKHURUQRWWKH\
DUHFRQVLGHUHG6$(VVSHFLILF&DUGLRYDVFXODU&9DQG'HDWKVHFWLRQVRIWKH&5)ZLOO
EHUHTXLUHGWREHFRPSOHWHG 7KHVHVHFWLRQVLQFOXGHTXHVWLRQVUHJDUGLQJFDUGLRYDVFXODU
LQFOXGLQJVXGGHQFDUGLDFGHDWKDQGQRQFDUGLRYDVFXODUGHDWK
7KH&9&5)VDUHSUHVHQWHGDVTXHULHVLQUHVSRQVHWRUHSRUWLQJRIFHUWDLQ&90HG'5$
WHUPV 7KH&9 LQIRUPDWLRQVKRXOGEHUHFRUGHGLQWKHVSHFLILFFDUGLRYDVFXODUVHFWLRQRI
WKH&5)ZLWKLQRQHZHHNRIUHFHLSWRID&9(YHQWGDWDTXHU\SURPSWLQJLWVFRPSOHWLRQ
7KH'HDWK&5)LVSURYLGHGLPPHGLDWHO\DIWHUWKHRFFXUUHQFHRURXWFRPHRIGHDWKLV
UHSRUWHG,QLWLDODQGIROORZXSUHSRUWVUHJDUGLQJGHDWKPXVWEHFRPSOHWHGZLWKLQ RQH
ZHHNRIZKHQWKHGHDWKLVUHSRUWHG

'LVHDVH5HODWHG(YHQWVDQGRU'LVHDVH5HODWHG2XWFRPHV1RW
4XDOLI\LQJDV6$(V
$Q\FOLQLFDOO\VLJQLILFDQWVDIHW\DVVHVVPHQWVWKDWDUHDVVRFLDWHGZLWKWKHXQGHUO\LQJ
GLVHDVHXQOHVVMXGJHGE\WKH,QYHVWLJDWRUWREHPRUHVHYHUHWKDQH[SHFWHGIRUWKH
VXEMHFW¶VFRQGLWLRQDUHQRW WREHUHSRUWHGDVQRQVHULRXV$'5VRU6$(V

5HJXODWRU\5HSRUWLQJ5HTXLUHPHQWVIRU6$(V
3URPSWQRWLILFDWLRQRI6$(VE\WKH,QYHVWLJDWRUWR*6.LVHVVHQWLDOVRWKDWOHJDO
REOLJDWLRQVDQGHWKLFDOUHVSRQVLELOLWLHVWRZDUGVWKHVDIHW\RIVXEMHFWVDQGWKHVDIHW\RID
SURGXFWXQGHUFOLQLFDOLQYHVWLJDWLRQDUHPHW7KLVZLOODOVRLQFOXGHSRWHQWLDO6$(V
LGHQWLILHGE\KRVSLWDOLVDWLRQDOHUWVWKURXJKWKHPHGLFDOUHFRUG
*6.KDVDOHJDOUHVSRQVLELOLW\WRQRWLI\ERWKWKHORFDOUHJXODWRU\DXWKRULW\DQGRWKHU
UHJXODWRU\DJHQFLHVDERXWWKHVDIHW\RIDSURGXFWXQGHUFOLQLFDOLQYHVWLJDWLRQ*6.ZLOO
FRPSO\ZLWKFRXQWU\VSHFLILFUHJXODWRU\UHTXLUHPHQWVUHODWLQJWRVDIHW\UHSRUWLQJWRWKH
UHJXODWRU\DXWKRULW\,QGHSHQGHQW(WKLFV&RPPLWWHH,(&DQG,QYHVWLJDWRUV
,QYHVWLJDWRUVDIHW\UHSRUWVDUHSUHSDUHGIRUVXVSHFWHGXQH[SHFWHGVHULRXVDGYHUVH
UHDFWLRQVDFFRUGLQJWRORFDOUHJXODWRU\UHTXLUHPHQWVDQG*6.SROLF\DQGDUHIRUZDUGHG
WRLQYHVWLJDWRUVDVQHFHVVDU\
$Q,QYHVWLJDWRUZKRUHFHLYHVDQLQYHVWLJDWRUVDIHW\UHSRUWGHVFULELQJD6$(VRURWKHU
VSHFLILFVDIHW\LQIRUPDWLRQHJVXPPDU\RUOLVWLQJRI6$(VIURP*6.ZLOOILOHLWZLWK
WKH,%DQGZLOOQRWLI\WKH,(&LIDSSURSULDWHDFFRUGLQJWRORFDOUHTXLUHPHQWV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
54
7KHPHWKRGRIGHWHFWLQJUHFRUGLQJHYDOXDWLQJDQGIROORZXSRI6$(VDQGQRQVHULRXV
$'5VSOXVSURFHGXUHVIRUFRPSOHWLQJDQGWUDQVPLWWLQJ6$(UHSRUWVWR*6.DUHSURYLGHG
LQWKH6303URFHGXUHVIRUSRVWVWXG\6$(VQRQVHULRXV$'5VDUHSURYLGHGLQWKH630
3URFHGXUHVIRUGRFXPHQWLQJWUDQVPLWWLQJDQGIROORZXSRIPHGLFDOGHYLFHLQFLGHQWV
DORQJZLWKWKHUHJXODWRU\UHSRUWLQJUHTXLUHPHQWVIRUPHGLFDOGHYLFHVDUHSURYLGHGLQWKH
630

3UHJQDQF\
!
'HWDLOVRIDOO SUHJQDQFLHVLQIHPDOHVXEMHFWVZLOOEHFROOHFWHGIURPWKHWLPHWKH
LQIRUPHGFRQVHQWLVVLJQHG9LVLWDQGXQWLOWKHHQGRIWKHVWXG\9LVLW
!
$Q\SUHJQDQF\WKDWRFFXUVGXULQJVWXG\SDUWLFLSDWLRQPXVWEHUHSRUWHGXVLQJD
FOLQLFDOWULDOSUHJQDQF\IRUP
!
,IDSUHJQDQF\LVUHSRUWHGWKHQWKHLQYHVWLJDWRUVKRXOGLQIRUP*6.ZLWKLQ
ZHHNVRIOHDUQLQJRIWKHSUHJQDQF\DQGVKRXOGIROORZWKHSURFHGXUHVRXWOLQHGLQ
$SSHQGL[
!
$Q\6$(RFFXUULQJLQDVVRFLDWLRQZLWKDSUHJQDQF\ EURXJKWWRWKH
LQYHVWLJDWRU¶VDWWHQWLRQDIWHUWKHVXEMHFWKDVFRPSOHWHGWKHVWXG\DQGFRQVLGHUHG
E\WKHLQYHVWLJDWRUDVSRVVLEO\UHODWHGWRWKHVWXG\WUHDWPHQWPXVWEHSURPSWO\
UHSRUWHGWR*6.

0HGLFDO'HYLFH,QFLGHQWV,QFOXGLQJ0DOIXQFWLRQV
0HGLFDOGHYLFHVVSLURPHWHUVZLOOEHSURYLGHGE\*6.IRUXVHLQWKLVVWXG\ +RZHYHU
QRQHRIWKHGHYLFHVSURYLGHGDUHPDQXIDFWXUHGE\RURQEHKDOIRI*6.

3K\VLFDO([DPV
$FRPSOHWHSK\VLFDOH[DPLQDWLRQZLOOLQFOXGHDWDPLQLPXPDVVHVVPHQWRIWKH
&DUGLRYDVFXODU 5HVSLUDWRU\*DVWURLQWHVWLQDODQG1HXURORJLFDOV\VWHPV
,QYHVWLJDWRUVVKRXOGSD\VSHFLDODWWHQWLRQWRFOLQLFDOVLJQVUHODWHGWRSUHYLRXVVHULRXV
LOOQHVVHV

9LWDO6LJQV
9LWDOVLJQPHDVXUHPHQWVZLOOLQFOXGHKHLJKWZHLJKWSXOVHUDWHV\VWROLFDQGGLDVWROLF
EORRGSUHVVXUH
9LWDOVLJQVZLOOEHPHDVXUHGDQGUHFRUGHGLQWKHH&5)DW6FUHHQLQJYLVLW9LVLWDWWKH
5DQGRPLVDWLRQ9LVLW'D\DW:HHN9LVLWDW:HHN9LVLWDQGDW(DUO\
:LWKGUDZDO9LVLWH[FHSWIRUKHLJKWDQGZHLJKWWKDWZLOOEHFROOHFWHGDW9LVLWRQO\

(OHFWURFDUGLRJUDP(&*
$Q(&*LVQRWUHTXLUHGSULRUWRHQWHULQJWKLVVWXG\7KHUHDUHQRRWKHUUHJXODU(&*V
UHTXLUHGE\WKLVSURWRFRO

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
55

&OLQLFDO6DIHW\/DERUDWRU\$VVHVVPHQWV
7KHUHDUHQRFOLQLFDOVDIHW\ODERUDWRU\DVVHVVPHQWUHTXLUHPHQWVIRUWKLVVWXG\
$Q\DEQRUPDOODERUDWRU\WHVWUHVXOWVKHPDWRORJ\FOLQLFDOFKHPLVWU\RUXULQDO\VLVRU
RWKHUVDIHW\DVVHVVPHQWVHJ(&*VUDGLRORJLFDOVFDQVYLWDOVLJQVPHDVXUHPHQWV
UHFRUGHGGXULQJDURXWLQHFOLQLFYLVLWLQFOXGLQJWKRVHWKDW ZRUVHQIURPEDVHOLQHDQGIHOW
WREHFOLQLFDOO\VLJQLILFDQWLQWKHPHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKH,QYHVWLJDWRUDUH
WREHUHFRUGHGDVQRQVHULRXV$'5VRU6$(VDVDSSURSULDWH

*HQHWLFV
,QIRUPDWLRQUHJDUGLQJJHQHWLFUHVHDUFKLVLQFOXGHGLQ$SSHQGL[

'$7$0$1$*(0(17
!
)RUWKLVVWXG\VXEMHFWGDWDZLOOEHHQWHUHGLQWR*6.GHILQHG&5)VWUDQVPLWWHG
HOHFWURQLFDOO\WR*6.RUGHVLJQHHDQGFRPELQHGZLWKGDWDSURYLGHGIURPRWKHU
VRXUFHVLQDYDOLGDWHGGDWDV\VWHP
!
0DQDJHPHQWRIFOLQLFDOGDWDZLOOEHSHUIRUPHGLQDFFRUGDQFHZLWKDSSOLFDEOH*6.
VWDQGDUGVDQGGDWDFOHDQLQJSURFHGXUHVWRHQVXUHWKHLQWHJULW\RIWKHGDWDHJ
UHPRYLQJHUURUVDQGLQFRQVLVWHQFLHVLQWKHGDWD
!
$GYHUVHHYHQWVDQGFRQFRPLWDQWPHGLFDWLRQVWHUPVZLOOEHFRGHGXVLQJ0HG'5$
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV DQGDQLQWHUQDOYDOLGDWHGPHGLFDWLRQ
GLFWLRQDU\*6.'UXJ
!
&5)VLQFOXGLQJTXHULHVDQGDXGLWWUDLOVZLOOEHUHWDLQHGE\*6.DQGFRSLHVZLOOEH
VHQWWRWKHLQYHVWLJDWRUWRPDLQWDLQ DVWKHLQYHVWLJDWRUFRS\6XEMHFWLQLWLDOVZLOOQRW
EHFROOHFWHGRUWUDQVPLWWHGWR*6.DFFRUGLQJWR*6.SROLF\

67$7,67,&$/&216,'(5$7,216$1''$7$
$1$/<6(6

+\SRWKHVHV
7KHREMHFWLYHRIWKHVWXG\LVWRFRPSDUHWKHHIILFDF\RIIOXWLFDVRQHIXURDWH))YLODQWHURO
9,,QKDODWLRQ3RZGHU))9,PFJPFJRU))9,PFJPFJZLWKXVXDO
,&6/$%$LQKDODWLRQGU\SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\RYHUVL[PRQWKVLQD
ODUJH)UHQFKSULPDU\DQG UHVSLUDWRU\VSHFLDOLVWFDUHSRSXODWLRQRIVXEMHFWVZLWKDVWKPD
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQHLQWKH$&7WRWDOVFRUH
DVVHVVHGDW:HHN9LVLW5HJDUGLQJWKHSULPDU\HIILFDF\HQGSRLQWLHWKHFKDQJH
IURPEDVHOLQHLQWKH$&7WRWDOVFRUHDVVHVVHGDW:HHN>9LVLW@WKHSULPDU\DQDO\VLV
ZLOOVKRZWKDWWKHIL[HGFRPELQDWLRQ))9,PFJPFJRUPFJPFJLVQRQ
LQIHULRUWRDQ\RWKHU,&6/$%$FRPELQDWLRQVLQLQKDODWLRQSRZGHUDVVXPLQJDQRQ
LQIHULRULW\PDUJLQRI1RQLQIHULRULW\ZLOOEHFODLPHGLIWKHWZRVLGHGFRQILGHQFH
LQWHUYDORQWKHGLIIHUHQFHLQPHDQSULPDU\HIILFDF\HQGSRLQWV))9,PLQXV&RPSDUDWRU
SUHFOXGHVWKHQRQLQIHULRULW\PDUJLQRI

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
56
,IDQGRQO\LIQRQLQIHULRULW\LVVLJQLILFDQWO\DFKLHYHGDW:HHN9LVLWZLWKUHJDUG
WRWKHSULPDU\HQGSRLQWWKHQ QRQLQIHULRULW\RIWKHIL[HGFRPELQDWLRQ))9,
PFJPFJRUPFJPFJWRDQ\RWKHU,&6/$%$FRPELQDWLRQVZLOOEHWHVWHGDW
:HHN9LVLWFRQVLGHULQJWKHVDPHQRQLQIHULRULW\PDUJLQRI1RQLQIHULRULW\
ZLOOEHFODLPHGLIWKHWZRVLGHGFRQILGHQFHLQWHUYDORQWKHGLIIHUHQFHLQPHDQ
SULPDU\HIILFDF\HQGSRLQWV))9,PLQXV&RPSDUDWRUDW:HHN9LVLWSUHFOXGHVWKH
QRQLQIHULRULW\PDUJLQRI
2IQRWHDVWKHWZRWHVWVIRUQRQLQIHULRULW\DUHVHTXHQWLDOO\SHUIRUPHGWKHFORVXUH
SULQFLSOHKROGVDQGWKHUHLVQRQHHGWRDGMXVWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
LHIRUHDFKWHVW

6DPSOH6L]H&RQVLGHUDWLRQV

6DPSOH6L]H$VVXPSWLRQV
5HVXOWVEDVHGRQWKH+=$VWXG\KDYHVKRZQWKDWWKHHVWLPDWHGVWDQGDUGGHYLDWLRQ
RIWKH FKDQJHLQ$&7VFRUHZDV8QSXEOLVKHGGDWDKDYHVKRZQWKDWWKHVWDQGDUG
GHYLDWLRQRIFKDQJHRI$&7UDQJHGIURPWR7KHUHIRUHDVRPHZKDWFRQVHUYDWLYH
FKRLFHRI6'RISRLQWLVUHWDLQHG
%DVHGRQWKHOLWHUDWXUH>6FKDW]@WKH0LQLPDOO\,PSRUWDQW'LIIHUHQFH0,'RIWKH
$&7FRXOGEHFRQVLGHUHGDVSRLQWV+DOIWKLV0,'LHFRXOGWKHUHIRUHEHXVHGWR
GHILQHWKHQRQLQIHULRULW\PDUJLQ
$VVXPLQJDSRLQWVWDQGDUGGHYLDWLRQIRUWKHFKDQJHLQ $&7WRWDOVFRUHDW:HHN
9LVLWDSRLQWQRQLQIHULRULW\PDUJLQDQGDWZRVLGHGQRPLQDOVLJQLILFDQFHOHYHO
RIWKHVDPSOHVL]HQHHGHGSHUJURXSWRDFKLHYHDWOHDVWDSRZHULVLHD
WRWDORIVXEMHFWV$VVXPLQJDGURSRXWUDWHDURXQGVXEMHFWVPXVWEH
UDQGRPL]HGHLWKHUWR))9,RUWRWKHDOWHUQDWLYH,&6/$%$LQUDWLRWRDFKLHYHDWOHDVW
DSRZHU

6DPSOH6L]H6HQVLWLYLW\
7RGHPRQVWUDWHWKHVHQVLWLYLW\RIWKHVDPSOHVL]HFDOFXODWLRQIRUWKLVVWXG\WKHIROORZLQJ
WDEOHSUHVHQWVWKHSRZHURIWKHVWXG\XQGHUGLIIHUHQWFLUFXPVWDQFHVLQWHUPVRIWKH
VWDQGDUGGHYLDWLRQ
7KHDVVXPSWLRQXVHGLVVKDGHG
6WDQGDUGGHYLDWLRQ
3RZHUIRUWKHVXEMHFWVHYDOXDEOH
1 











2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
57

6DPSOH6L]H5HHVWLPDWLRQRU$GMXVWPHQW
1RWSODQQHG

'DWD$QDO\VLV&RQVLGHUDWLRQV

$QDO\VLV3RSXODWLRQV
3RSXODWLRQVFRQVLGHUHGIRUDQDO\VLVDUHDVIROORZV
,QWHQWWRWUHDW,77SRSXODWLRQ$OOUDQGRPL]HGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQH
GRVHRIWKHSUHVFULSWLRQRIVWXG\PHGLFDWLRQ HLWKHU))9,RUXVXDO,&6/$%$DVWKPD
PDLQWHQDQFHWKHUDS\7KH,77SRSXODWLRQ ZLOOEHXVHGWRDQDO\]HWKHSULPDU\HIILFDF\
HQGSRLQWDQDO\VLVWKHVHFRQGDU\HIILFDF\HQGSRLQWDQGRWKHUHIILFDF\HQGSRLQWV6XEMHFWV
ZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVUDQGRPL]HGIRUWKH,77SRSXODWLRQ
3HUSURWRFRO33SRSXODWLRQ DOO,77VXEMHFWVZLWKRXWDQ\PDMRUYLRODWLRQVRIVWXG\
SURFHGXUHV0DMRUSURWRFROYLRODWLRQVZLOOEHLGHQWLILHGSULRUWRGDWDEDVHORFN3URWRFRO
GHYLDWLRQVZLOOEHUHYLHZHGDQGFODVVLILHGDVPLQRURUPDMRUGXULQJDGDWDUHYLHZ
PHHWLQJWKDWZLOOEHKHOGEHIRUHGDWDEDVHORFN7KHH[FOXVLRQRIVXEMHFWVIURPWKH33
SRSXODWLRQ ZLOOEHVSHFLILHGDQGGRFXPHQWHGLQWKH5$3
6DIHW\SRSXODWLRQ $OOHQUROOHGVXEMHFWVKDYLQJ UHFHLYHGDWOHDVWRQHGRVHRIWKH
SUHVFULSWLRQRIVWXG\PHGLFDWLRQHLWKHU))9,RUXVXDO,&6/$%$DVWKPDPDLQWHQDQFH
WKHUDS\DQGFRQVLGHUHGDVWUHDWHG7KH6DIHW\SRSXODWLRQ ZLOOEHWKHEDVLVIRUVDIHW\
DQDO\VHV6XEMHFWVZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVWUHDWHGIRUWKH6DIHW\
SRSXODWLRQ
'HWDLOVRIWKHDQDO\VLVGDWDVHWVWREHFUHDWHGZLOOEHVSHFLILHGLQWKH5HSRUW$QDO\VLV3ODQ
5$3

,QWHULP$QDO\VLV
1RWDSSOLFDEOH

.H\(OHPHQWVRI$QDO\VLV3ODQ
7KHSULPDU\FRPSDULVRQRILQWHUHVWLVWKHFRPSDULVRQRIWKHFKDQJHIURPEDVHOLQH9LVLW
LQWKHWRWDO$&7VFRUHDVVHVVHGDW:HHN9LVLWEHWZHHQ))9,PFJPFJRU
PFJPFJDQGXVXDO,&6/$%$LQKDODWLRQSRZGHUIRUDVWKPDPDLQWHQDQFH
WKHUDS\
7KHSULPDU\VHWIRUDQDO\VLVZLOOEHSHUIRUPHGRQWKHLQWHQWWRWUHDWSRSXODWLRQ$
VHQVLWLYLW\DQDO\VLVZLOOEHSHUIRUPHGLQWKH33SRSXODWLRQ
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHVLGHGQRPLQDOOHYHO
RIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,WR
,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
58
,IDQGRQO\LIQRQLQIHULRULW\LVDFKLHYHGIRUWKHSULPDU\HQGSRLQWDW:HHN9LVLW
WKHQWKHNH\VHFRQGDU\HQGSRLQWLHWKHFKDQJHIURPEDVHOLQHLQWKHWRWDO$&7VFRUH
DVVHVVHGDW:HHN9LVLWZLOOEHWHVWHG$W:HHN9LVLWQRQLQIHULRULW\RI
))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORI
VLJQLILFDQFH,I1RQLQIHULRULW\LVDFKLHYHGWKHQVXSHULRULW\RI ))9,WR,&6/$%$ZLOO
VWLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
2IQRWHWKLVVWHSGRZQWHVWLQJSURFHGXUHVWLOOVWURQJO\FRQWUROVWKHRYHUDOOW\SH,HUURUDW
WKHWZRVLGHGOHYHO
'HILQLWLRQRIWKHWUHDWPHQWIDLOXUHZLOOEHDVIROORZ
!
7UHDWPHQWZLWKGUDZDO
!
&KDQJHRIWUHDWPHQW
!
'RVHLQFUHDVHEH\RQGWKHPD[LPXPDOORZHGGDLO\GRVHLQWKH(8OLFHQVHIRU
))9,!PFJPFJIRU)36!PFJWZLFHGDLO\IRU%8')!PFJ
WZLFHGDLO\
2WKHU&RPSDULVRQVRI,QWHUHVW2WKHUHIILFDF\HQGSRLQWVDQGVDIHW\HQGSRLQWVZLOOEH
GHVFULEHG(VWLPDWHGGLIIHUHQFHVEHWZHHQJURXSVZLWKFRQILGHQFHLQWHUYDOVZLOOEH
SURYLGHGZKHQDSSOLFDEOH
'DWDZLOOEHOLVWHGDQGVXPPDUL]HGDFFRUGLQJWRWKH*6.UHSRUWLQJVWDQGDUGVZKHUH
DSSOLFDEOH&RPSOHWHGHWDLOVZLOOEHGRFXPHQWHGLQWKH5HSRUWLQJ$QDO\VLV3ODQ5$3
$Q\GHYLDWLRQVIURPRUDGGLWLRQVWRWKHRULJLQDODQDO\VLVSODQGHVFULEHGLQWKLVSURWRFRO
ZLOOEHGRFXPHQWHGLQWKH5$3DQGILQDOVWXG\UHSRUW'HVFULSWLYHVXPPDULHVZLOOEH
SURYLGHGE\WUHDWPHQWJURXS
'HPRJUDSKLFDQGEDVHOLQHFKDUDFWHULVWLFVZLOOEHVXPPDUL]HG
&RQWLQXRXVYDULDEOHV ZLOOEHVXPPDUL]HGXVLQJGHVFULSWLYHVWDWLVWLFVQXPEHURIREVHUYHG
DQGPLVVLQJGDWDPHDQVWDQGDUGGHYLDWLRQ6'PHGLDQ44PLQLPXPDQG
PD[LPXP
&DWHJRULFDOYDULDEOHV ZLOOEHVXPPDUL]HGDVQXPEHUVRIREVHUYHGDQGPLVVLQJGDWD
FRXQWVDQGSHUFHQWDJHIRUHDFKFDWHJRU\UHSRUWHGWRWKHQXPEHURIQRQPLVVLQJYDOXHV
)RUELQDU\YDULDEOHVFRQILGHQFHLQWHUYDOVIRUSURSRUWLRQVZLOOEHHVWLPDWHGEDVHGRQ
WKH&ORSSHU3HDUVRQPHWKRG
7KHFRQWUDVWEHWZHHQ))9,DQGXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\LQ
LQKDODWLRQSRZGHUZLOOEHRISULPDU\LQWHUHVWIRUDOOHIILFDF\HQGSRLQWV
1RQLQIHULRULW\RI))9,YHUVXVXVXDO,&6/$%$DVWKPDWKHUDS\ZLOOEHILUVWWHVWHGDW
:HHN9LVLW,IDQGRQO\LIVLJQLILFDQFHLVDFKLHYHGDW:HHN9LVLWWKHQQRQ
LQIHULRULW\ZLOOEHWHVWHGDW:HHN9LVLWDWWKHWZRVLGHGOHYHORIVLJQLILFDQFH
7KLVVWHSGRZQWHVWLQJSURFHGXUHVWURQJO\FRQWUROVWKHRYHUDOOW\SH,HUURUDWWKH
WZRVLGHGOHYHO

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
59
,IQRQLQIHULRULW\LVDFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI))9,YHUVXVXVXDO
,&6/$%$DVWKPDWKHUDS\ZLOOEHWHVWHGDWWKHVDPHWZRVLGHGQRPLQDOVLJQLILFDQFH
OHYHORI ,IQRQLQIHULRULW\LVDFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI
))9,YHUVXVXVXDO,&6/$%$DVWKPDWKHUDS\ZLOOEHWHVWHGDWWKHVDPHWZRVLGHG
QRPLQDOVLJQLILFDQFHOHYHORI
%DVHOLQH$&7VFRUHZLOOEHLQFOXGHGLQWKHSULPDU\HIILFDF\DQDO\VHV*HQGHUDJHVWXG\
VLWHDQGSRWHQWLDOO\VHDVRQDWUDQGRPL]DWLRQ ZLOOEHIXUWKHULQYHVWLJDWHGLQVHQVLWLYLW\
DQDO\VHVZKHQDSSURSULDWH2WKHUFRYDULDWHVPD\EHFRQVLGHUHGDQGLIVRLWZLOOEH
GHWDLOHGLQWKH5$3
7UHDWPHQWE\SURJQRVWLFIDFWRUVLQWHUDFWLRQVZLOOEHVSHFLILFDOO\LQYHVWLJDWHGLQVHFRQGDU\
PRGHOV
+DQGOLQJRIWUHDWPHQWZLWKGUDZDOWUHDWPHQWZLWKGUDZDOZLOOEHFRQVLGHUHGDVDIDLOXUH
DQGWKHSULPDU\HQGSRLQWDWWKHWUHDWPHQWZLWKGUDZDOWLPHZLOOEHDVVHVVHGEDVHGRQWKH
ODVWDYDLODEOH$&7SRVWUDQGRPL]DWLRQVFRUHEHIRUHZLWKGUDZDO2IQRWHDFKDQJHLQWKH
GRVHUHJLPHQZLOOQRWEHFRQVLGHUHGDVDWUHDWPHQWIDLOXUH
+DQGOLQJRIPLVVLQJGDWDDVDJHQHUDOUXOHPLVVLQJGDWDZLOOQRWEHUHSODFHG
1HYHUWKHOHVVVHQVLWLYLW\DQDO\VHVUHJDUGLQJWKHSULPDU\DQG NH\VHFRQGDU\HQGSRLQWZLOO
UHSODFHPLVVLQJ$&7DVVHVVPHQWVE\WKHODVWDYDLODEOHSRVWUDQGRPL]DWLRQ$&7YDOXH
LHEDVHGRQWKHODVWREVHUYDWLRQFDUULHGIRUZDUGPHWKRG
7KHVWXG\LVDGHTXDWHO\SRZHUHGIRUWKHSULPDU\DQGWKHNH\VHFRQGDU\HQGSRLQWLHWR
VKRZQRQLQIHULRULW\RI))9,WRFXUUHQW,&6/$%$DW:HHN9LVLWDQGDW:HHN
9LVLWFRQVLGHULQJDQRQLQIHULRULW\PDUJLQRI2WKHUVHFRQGDU\HQGSRLQWVDUHQRW
QHFHVVDULO\DGHTXDWHO\SRZHUHGDQGDGHVFULSWLYHDQDO\VLVZLOORQO\EHSURSRVHGIRUWKHVH
HQGSRLQWV
7KHSULPDU\HIILFDF\DQDO\VLVSRSXODWLRQVHWLVGHILQHGDVDOOVXEMHFWVEHORQJLQJWRWKH
,QWHQWWR7UHDWSRSXODWLRQ,77ZKLFKLQFOXGH DOOVXEMHFWVZKRKDYHEHHQUDQGRPLVHG
DQGUHFHLYHGDWOHDVWRQHSUHVFULSWLRQRIVWXG\PHGLFDWLRQHJ))9,RUXVXDO
,&6/$%$LQKDODWLRQSRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\
(DFKVXEMHFWZLOOFRPSOHWHWKH$&7DW9LVLW5DQGRPLVDWLRQ:HHN9LVLWDQG
:HHN9LVLW$&7VFRUHVZLOODOVREHDVVHVVHGDW:HHN9LVLWDQGDW:HHN
9LVLWDQGDWWKHZLWKGUDZDOWLPHLIDQ\

3ULPDU\$QDO\VHV
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7WRWDO
VFRUHDVVHVVHGDW:HHN9LVLW
7KHSULPDU\SRSXODWLRQ RIDQDO\VLVZLOOEHWKH,77SRSXODWLRQ
,IWUHDWPHQWLVZLWKGUDZQWKHQWKHPLVVLQJ$&7VFRUHDWWKHQHDUHVWYLVLWDIWHUWUHDWPHQW
ZLWKGUDZDOZLOOEHUHSODFHGE\WKH$&7VFRUHDVVHVVHGDWZLWKGUDZDOWLPH,IQR$&7

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
60
VFRUHLVDVVHVVHGDWZLWKGUDZDOWLPHWKHQWKH$&7PLVVLQJVFRUHDWWKHQHDUHVWYLVLWDIWHU
WUHDWPHQWZLWKGUDZDOZLOOQRWEHUHSODFHG

1RQLQIHULRULW\WHVWLQJ
7KHQRQLQIHULRULW\RI))9,YHUVXVDQ\RWKHU,&6/$%$'3,FRPSDUDWRUZLOOEH
SULPDULO\WHVWHGLQDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFK7KHPRGHOZLOO
LQFOXGHIDFWRUVDQGFRYDULDWHVDVIROORZWUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN
DQG:HHNEDVHOLQH $&7WUHDWPHQWE\YLVLWLQWHUDFWLRQEDVHOLQH$&7E\YLVLW
LQWHUDFWLRQJHQGHUDJHDQGSDWLHQWZLOOEHILWWHGDVDUDQGRPIDFWRU7KH5HVWULFWHG
0D[LPXP/LNHOLKRRG5(0/HVWLPDWLRQDSSURDFKZLOOEHXVHGDQGWKHGHIDXOW
FRYDULDQFHVWUXFWXUHZLOOEHXQVWUXFWXUHG&RQVLVWHQWZLWK0050PRGHOILWWLQJQR
H[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUDJLYHQWLPHSRLQWZLOOEHSHUIRUPHG7KH
FRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRUZLOO
EHHVWLPDWHGDW:HHN9LVLWLQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHGLIWKH
QRQLQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQ
WKHGLIIHUHQFHEHWZHHQ))9,DQGDQ\RWKHUFRPSDUDWRUSRVLWLYHYDOXHVRIWKHGLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\DQDO\VHV
D
+DQGOLQJPLVVLQJGDWD
:KLOHVXEMHFWVPLVVLQJ:HHN9LVLWGDWDEXWKDYLQJHDUOLHUGDWDZLOOEHLQFOXGHGLQ
WKH0050SULPDU\DQDO\VLVWKHLQWHUSUHWDELOLW\RIWKHUHVXOWVIURPWKHSULPDU\PRGHO
ZLOOGHSHQGRQWKHPLVVLQJGDWDVDWLVI\LQJWKH0LVVLQJDW5DQGRP0$57RVXSSRUW
WKHYDOLGLW\RIWKHFRQFOXVLRQVGUDZQIURPWKLVDQDO\VLVVHYHUDOVHQVLWLYLW\DQDO\VHVZLOO
EHSHUIRUPHGWRH[SORUHWKHGURSRXWSDWWHUQDQGLWVSRVVLEOHLPSDFWRQWUHDWPHQW
FRPSDULVRQV

0LVVLQJYDOXHVDW:HHN9LVLWZLOOEHUHSODFHGE\WKHSRVWUDQGRPL]DWLRQ
ODVWDYDLODEOHYDOXHHLWKHUWKHZHHNEDVHG$&7VFRUHRUWKH$&7VFRUHDW
WUHDWPHQWZLWKGUDZDOWLPHLI DQ\LHEDVHGRQWKH/DVW2EVHUYDWLRQ&DUULHG
)RUZDUGPHWKRG7KHFKDQJHIURPEDVHOLQHLQ$&7DW:HHN9LVLWZLOOEH
DQDO\]HGLQDQ$1&29$PRGHODGMXVWLQJIRUWUHDWPHQWDQGEDVHOLQH$&7VFRUH
7KHWUHDWPHQWHIIHFW))9,YHUVXVDQ\RWKHU,&6/$%$FRPSDUDWRUDQGLWV
FRUUHVSRQGLQJFRQILGHQFHLQWHUYDOZLOOEHHVWLPDWHGLQWKLVPRGHOWRWHVWWKH
QRQLQIHULRULW\K\SRWKHVLV

0XOWLSOHLPSXWDWLRQ0,DQDO\VHVXWLOL]LQJFRYDULDWHVNQRZQWREHSUHGLFWLYHRI
UHVSRQVHVHDVRQDWUDQGRPL]DWLRQREVHUYHGYDOXHRI$&7DW:HHNREVHUYHG
YDOXHRI$&7DW:HHN9LVLW2WKHUFRYDULDWHVPD\EHFRQVLGHUHGDQGLIVR
LWZLOOEHGHWDLOHGLQWKH5$3
6WHS)RUHDFKWUHDWPHQWJURXSVHSDUDWHO\PLVVLQJPHDVXUHPHQWVDUHLPSXWHGIRU
VXEMHFWVZLWKDEDVHOLQH PHDVXUHPHQWZKHUHWKHUHDUHPLVVLQJREVHUYDWLRQVDWHLWKHU
:HHNRU:HHNXVLQJWKHDERYHFRYDULDWHVDQGUHJUHVVLRQEDVHGLPSXWDWLRQPHWKRG
7KH0DUNRY&KDLQ0RQWH&DUOR0&0&PHWKRGIRU0,ZLOOEHXVHGDQGWHQVXFKVHWV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
61
RILPSXWHGGDWDZLOOEHFUHDWHGHDFKZLWKWKHREVHUYHGYDOXHVRULPSXWHGYDOXHVIRU
VXEMHFWVZLWKPLVVLQJREVHUYDWLRQV
6WHS(DFKLPSXWHGGDWDVHWZLOOEHDQDO\]HGXVLQJWKHSULPDU\0050PRGHO7KH
WUHDWPHQWHIIHFWIURPWKHVHDQDO\VHVZLOOWKHQEHSRROHGXVLQJVWDQGDUG0,WKHRU\WR
PDNHDQRYHUDOOLQIHUHQFH7KHGLIIHUHQFHLQWKHOHDVWVTXDUHVPHDQVEHWZHHQWKHWZR
JURXSVDW:HHN9LVLWDQGWKHFRUUHVSRQGLQJFRQILGHQFHLQWHUYDOIRUWKH
GLIIHUHQFHZLOOEHSUHVHQWHG
E
$ VHQVLWLYLW\ DQDO\VLV EDVHG RQ WKH VHPL SDUDPHWULF +RGJHV/HKPDQQ +/
DSSURDFKZLOOEHSURSRVHGWRDVVHVVWKHUREXVWQHVVRIWKH00500RGHOEDVHG
QRQLQIHULRULW\UHVXOWV7KH+/GLIIHUHQFHEHWZHHQJURXSVZLWKWKHFRUUHVSRQGLQJ
FRQILGHQFHLQWHUYDOZLOOEHSURYLGHG
F
6HQVLWLYLW\ DQDO\VHV IRU KDQGOLQJ WUHDWPHQW ZLWKGUDZDO ZKHQ WUHDWPHQW
ZLWKGUDZDORFFXUVDQDOWHUQDWLYHPHWKRGIRULPSXWLQJWKHPLVVLQJYDOXHDWWKH
QHDUHVWYLVLWDIWHUZLWKGUDZDOWLPHZLOOEHSURSRVHGWKHSULPDU\HQGSRLQWPLVVLQJ
YDOXHZLOOEHHVWLPDWHGE\WKHZRUVW$&7VFRUHREVHUYHGEHWZHHQEDVHOLQHYLVLW
LQFOXGHGDQGZLWKGUDZDOWLPHLQFOXGHG
G
7KH SULPDU\ DQDO\VLV LH EDVHG RQ WKH 0050 DSSURDFK DQG WKH VDPH
VHQVLWLYLW\DQDO\VHVSUHVHQWHGKHUHDERYHZLOOEHSHUIRUPHGRQWKH3HU3URWRFRO
SRSXODWLRQ
0RGHODVVXPSWLRQVFKHFNLQJ
D $VVXPSWLRQV XQGHUO\LQJ WKH 0050 UHVS $1&29$ IRU WKH VHQVLWLYLW\ DQDO\VLV
PRGHOUHVLGXDOQRUPDOLW\ OLQHDUUHODWLRQVKLSEHWZHHQUHVSRQVH DQGEDVHOLQH$&7
HWFZLOOEHFKHFNHGZLWKJUDSKLFDOPHWKRGVSORWVRIVWXGHQWL]HGUHVLGXDOVHWF
E %DVHOLQH$&7ZLOOEH FDWHJRUL]HGDFFRUGLQJWKHGLVWULEXWLRQTXDUWLOHVDQGWKHVDPH
0050PRGHOUHVS$1&29$IRUWKHVHQVLWLYLW\DQDO\VLVDGMXVWLQJIRUFDWHJRUL]HG
%DVHOLQH$&7ZLOOEHILWWHGDJDLQ
F 3RVVLEOHWUHDWPHQWE\FRYDULDWHVEDVHOLQH$&7EDVHOLQH$VWKPDWKHUDS\VHDVRQDW
UDQGRPLVDWLRQ LQWHUDFWLRQ ZLOO EH LQYHVWLJDWHG 0050 UHVS $1&29$ IRU WKH
VHQVLWLYLW\DQDO\VLVDGMXVWLQJIRUWKHVHDGGLWLRQDOLQWHUDFWLRQWHUPV
G 7KH LQIOXHQFH RI WKH FRYDULDWHV DQG SRWHQWLDO DGGLWLRQDO FRYDULDWHV RQ WKH RXWFRPH
ZLOOEHLQYHVWLJDWHG

6XSHULRULW\WHVWLQJ
,IQRQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI))9,
WRDQ\RWKHUFRPSDUDWRUZLOOEHWHVWHGDWWKHXVXDOWZRVLGHGQRPLQDOOHYHORI
VLJQLILFDQFH
7KHVDPHPRGHOVDQGDQDO\VHVPHQWLRQHGDERYHZLOOEHXVHGWRDVVHVVWKHVXSHULRULW\
K\SRWKHVLV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
62

6HFRQGDU\$QDO\VHV
.H\VHFRQGDU\DQDO\VLV
7KHNH\VHFRQGDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7
WRWDOVFRUHDVVHVVHGDW:HHN9LVLW

1RQLQIHULRULW\WHVWLQJ
,IQRQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGDW:HHN9LVLWWKHQQRQLQIHULRULW\ZLOO
EHWHVWHGDW:HHNDWWKHWZRVLGHGQRPLQDOOHYHO,IQRQLQIHULRULW\LVQRW
DFFHSWHGDW:HHN9LVLWQRQLQIHULRULW\ZLOOQRWEHWHVWHGDW:HHN9LVLWDQG
DVVHVVHGRQDGHVFULSWLYHEDVLVRQO\
0RUHSUHFLVHO\WKHNH\VHFRQGDU\HQGSRLQWDVVHVVHGDW:HHN9LVLWZLOODOVREH
DQDO\]HGXVLQJDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFKZKHUHGDWDXSWR
DQGLQFOXGLQJ:HHN9LVLWZLOOEHXVHGLQWKHPRGHO7KHPRGHOZLOOLQFOXGH
IDFWRUVDQGFRYDULDWHVDVIROORZWUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN:HHN
:HHNDQG:HHNEDVHOLQH $&7WUHDWPHQWE\YLVLWLQWHUDFWLRQEDVHOLQH$&7E\
YLVLWLQWHUDFWLRQJHQGHUDJHDQGSDWLHQWZLOOEHILWWHGDVDUDQGRPIDFWRU7KH5HVWULFWHG
0D[LPXP/LNHOLKRRG5(0/HVWLPDWLRQDSSURDFKZLOOEHXVHGDQGWKHGHIDXOW
FRYDULDQFHVWUXFWXUHZLOOEHXQVWUXFWXUHG&RQVLVWHQWZLWK0050PRGHOILWWLQJQR
H[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUDJLYHQWLPHSRLQWZLOOEHSHUIRUPHG7KH
FRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRUZLOO
EHHVWLPDWHGDW:HHN LQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHGLIWKHQRQ
LQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQWKH
GLIIHUHQFHEHWZHHQ))9,DQGDQ\RWKHUFRPSDUDWRUSRVLWLYHYDOXHVRIWKHGLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\ DQDO\VHV WKH VDPH VHQVLWLYLW\ DQDO\VHV DV WKRVH GHVFULEHG DERYH IRU WKH
SULPDU\HQGSRLQWZLOOEHSHUIRUPHGIRUWKHNH\VHFRQGDU\HIILFDF\HQGSRLQW
0RGHODVVXPSWLRQVFKHFNLQJWKHDQDO\VHVSURSRVHGWRFKHFNPRGHODVVXPSWLRQVIRUWKH
DQDO\VLVRIWKHNH\VHFRQGDU\HIILFDF\HQGSRLQWZLOOEHWKHVDPHDVWKRVHGHVFULEHGDERYH
IRUWKHSULPDU\HQGSRLQW

6XSHULRULW\WHVWLQJ
,IQRQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI))9,
YHUVXVDQ\RWKHUFRPSDUDWRUZLOOEHWHVWHGDWWKHXVXDOWZRVLGHGQRPLQDOOHYHORI
VLJQLILFDQFH
7KHVDPHPRGHOVDQGDQDO\VHVPHQWLRQHGDERYHZLOOEHXVHGWRDVVHVVWKHVXSHULRULW\
K\SRWKHVLV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
63
2WKHUVHFRQGDU\DQDO\VHV
3URSHUXVHRIWKHPHGLFDOGHYLFH
7KHRWKHUNH\VHFRQGDU\HQGSRLQWZLOOEHWKHFRUUHFWXVHRIWKHLQKDOHUGHYLFHDVVHVVHGDW
UDQGRPLVDWLRQ9LVLWDW:HHN9LVLWDQGDW:HHN9LVLW7KHGHYLFHZLOO
EHFRQVLGHUHGDVDGHTXDWHO\XVHGLIWKHSDWLHQWGLGQ¶WPDNHDQ\FULWLFDOHUURU DWWKH
FRUUHVSRQGLQJYLVLWVUDQGRPLVDWLRQ>9LVLW@ZHHN>9LVLW@DQGZHHN>9LVLW@
3URSRUWLRQVRIVXEMHFWVFRUUHFWO\XVLQJWKHGHYLFHZLOOEHHVWLPDWHGZLWKLQHDFKJURXS$
FRUUHVSRQGLQJFRQILGHQFHLQWHUYDORIWKHGLIIHUHQFHLQSURSRUWLRQVZLOODOVREH
SURYLGHG$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOOEHGHWDLOHGLQWKH
5$3(YHQLIWHVWVZLOOEHSHUIRUPHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVH
DQDO\VHV

2WKHU$QDO\VHV
2WKHU$QDO\VHV
7KHDQDO\VLVRIWKHRWKHUHQGSRLQWVGHILQHGLQWKLVVHFWLRQZLOOEHSURYLGHGIRU
H[SORUDWRU\SXUSRVHVRQO\$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOO
EHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGDQGFRQILGHQFHLQWHUYDOVZLOO
EHSURYLGHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
64
&KDQJHIURPEDVHOLQHLQSUHGRVHWURXJK)(9
5HVXOWVZLOOEHVXPPDUL]HGIRUHDFKJURXSDW:HHN9LVLW 0RUHGHWDLOZLOOEH
SURYLGHGLQWKH5$3
5HVSRQVHWRWUHDWPHQW
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW25DSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7FKDQJH
7KHUHVSRQGHUDQDO\VHVZLOOEHFRQGXFWHGXVLQJDORJLVWLFUHJUHVVLRQPRGHODWDJLYHQ
9LVLWRU3KRQH&DOODGMXVWLQJIRUWUHDWPHQWDQGVWUDWLILFDWLRQIDFWRUVEDVHOLQH$&7VFRUH
FDWHJRUL]HGLQWRWZRFODVVHVEDVHOLQHDVWKPDWKHUDS\DQGSRWHQWLDOO\VHDVRQDW
UDQGRPL]DWLRQ7UHDWPHQWE\VWUDWLILFDWLRQIDFWRUVLQWHUDFWLRQHIIHFWVZLOOEHIXUWKHU
LQYHVWLJDWHGLQDGGLWLRQDOORJLVWLFPRGHOVDGMXVWLQJ IRUWKHVHVSHFLILFHIIHFWV
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW
7KHIUHTXHQF\DQGWKHSHUFHQWDJHRIVXEMHFWVZLWK$&7VFRUHDWDJLYHQYLVLWZLOOEH
GHVFULEHGE\WUHDWPHQWJURXS0RUHGHWDLOZLOOEHSURYLGHGLQWKH5$3
!
&KDQJHIURPEDVHOLQHLQLQGLYLGXDOTXHVWLRQVFRUHVIRU$&7DWDJLYHQYLVLW
)RU HDFK TXHVWLRQ WKH VWDWLVWLFDO SDUDPHWHUV RI WKH FKDQJHV ZLOO EH VXPPDUL]HG E\
WUHDWPHQWJURXS0RUHGHWDLOZLOOEHSURYLGHGLQWKH5$3
$GKHUHQFHZLWKVWXG\PHGLFDWLRQ
!
1XPEHURISHUFHQWDJHRIPHGLFDWLRQVGLVSHQVHGDQGFROOHFWHGGXULQJWKHVWXG\ZLOO
EHWDEXODWHGIRUHDFKYLVLWDQGE\WUHDWPHQWJURXS
!
7KHVFRUHIRU0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$DW'D\
:HHNDQG:HHNZLOOEHGHVFULEHGE\WUHDWPHQWJURXS
6HYHUHDVWKPDH[DFHUEDWLRQV
!
1XPEHURIVXEMHFWVZLWK DWOHDVWRQHVHYHUHH[DFHUEDWLRQQXPEHURIVHYHUHDVWKPD
H[DFHUEDWLRQDQGDQQXDOH[DFHUEDWLRQUDWHRYHUWKHVWXG\SHULRG
$VHYHUH DVWKPDH[DFHUEDWLRQLVGHILQHGDVGHWHULRUDWLRQRIDVWKPDUHTXLULQJWKHXVHRI
V\VWHPLFFRUWLFRVWHURLGV WDEOHWVVXVSHQVLRQRULQMHFWLRQZLWKRUZLWKRXWDQWLELRWLFV
SUHVFULEHGRUDQLQSDWLHQWKRVSLWDOLVDWLRQRUHPHUJHQF\GHSDUWPHQWYLVLWGXHWRDVWKPD
WKDWUHTXLUHGV\VWHPLFFRUWLFRVWHURLGVRUDQWLELRWLFV 
7KHQXPEHUDQGSHUFHQWDJHRIVXEMHFWVH[SHULHQFLQJDQDVWKPD H[DFHUEDWLRQGXULQJWKH
VWXG\SHULRGZLOOEHVXPPDUL]HGIRUHDFKWUHDWPHQWJURXS/LVWLQJZLOOEHSURYLGHGWR
LQFOXGHWKHSULPDU\FDXVHVRIWKHH[DFHUEDWLRQ
,IIHDVLEOHLHLIWKHQXPEHURIH[DFHUEDWLRQHYHQWVLVKLJKHQRXJKPHDQDQQXDOUDWHRI
DVWKPDH[DFHUEDWLRQZLOOEHDQDO\VHGXVLQJDJHQHUDOLVHGOLQHDUPRGHODVVXPLQJWKH
QHJDWLYHELQRPLDOGLVWULEXWLRQZLWKWKHORJDULWKPRIWLPHRQWUHDWPHQWDVDQRIIVHW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
65
YDULDEOH7KHDGMXVWHGPHDQUDWHVSHU\HDUWUHDWPHQWUDWLRDQGDVVRFLDWHGSYDOXHDQG
FRQILGHQFHLQWHUYDOZLOOEHSUHVHQWHG
+HDOWK5HODWHG4XDOLW\RI/LIHDQG+HDOWKVWDWXV
!
$QLQFUHDVHIURPEDVHOLQHRILQ$4/4VWRWDOVFRUHDW:HHN9LVLW
!
$QLQFUHDVHIURPEDVHOLQHRILQ$4/4VHQYLURQPHQWDOVWLPXOLGRPDLQVFRUH
DW:HHN9LVLW
!
&KDQJH IURP EDVHOLQH LQ WRWDO VFRUH DQG GRPDLQ VFRUHV RI $4/46 DW :HHN 
9LVLW
!
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ LQFUHDVH IURP EDVHOLQH RI   LQ $4/46
,QGLYLGXDOGRPDLQVFRUHVDW:HHN9LVLW
!
+HDOWKVWDWXVXVLQJWKH(XUR4RO4XHVWLRQQDLUH (4'DW:HHN9LVLW
3DWLHQWV6DWLVIDFWLRQDQG3UHIHUHQFHZLWKWKHLQKDOHU3$6$34XHVWLRQQDLUHVHH
$SSHQGL[
7KHRYHUDOOLQKDOHUVDWLVIDFWLRQDQGSUHIHUHQFHZLOOEHPHDVXUHGDW:HHN9LVLW
7KH3$6$3VFRUHZLOOEHVXPPDULVHGE\WUHDWPHQWJURXS
)XUWKHUDQDO\VHVZLOOEHVSHFLILHGLQWKH5HSRUW$QDO\VLV3ODQ
6XEJURXS $QDO\VHV
6XEJURXSVXPPDULHVDQGRUDQDO\VHVZLOODOVREHSURYLGHGZKHQDSSURSULDWHIRU
HIILFDF\DQGVDIHW\HQGSRLQWV EDVHGRQEDVHOLQHGLVHDVHFKDUDFWHULVWLFV
$GGLWLRQDODQDO\VHVFRXOGEHFDUULHGRXWXVLQJDSSURSULDWHPHWKRGVWRDFFRXQWIRU
FKDQJHVLQWUHDWPHQWGXULQJWKHFRXUVHRIWKHVWXG\)XUWKHUGHWDLOVZLOOEHSURYLGHGLQ
WKHDQDO\VLVSODQ
7KHGHWDLOVZLOOEHSURYLGHGLQWKH5$3
6DIHW\$QDO\VHV
6DIHW\GDWDZLOOEHVXPPDUL]HGDQGRUOLVWHGE\WUHDWPHQWJURXSDQGE\YLVLWIRUWKH
6DIHW\SRSXODWLRQ
([WHQWRI([SRVXUH
([WHQWRIH[SRVXUHWRVWXG\WUHDWPHQWLHQXPEHURIGD\VRQUDQGRPLVHGWUHDWPHQWZLOO
EHVXPPDULVHGE\WUHDWPHQWJURXSXVLQJPHDQVWDQGDUGGHYLDWLRQPHGLDQPLQLPXP
DQGPD[LPXP,QDGGLWLRQGXUDWLRQRIVXEMHFWH[SRVHGWRVWXG\GUXJZLOOEH VXPPDULVHG
DFURVVWUHDWPHQWJURXSV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
66
$GYHUVH'UXJ5HDFWLRQV
$GYHUVHGUXJUHDFWLRQVGXULQJWKHWUHDWPHQWSHULRGDQGGXULQJWKHSRVWWUHDWPHQWSHULRG
ZLOOEHVXPPDULVHGDQGGLVSOD\HGE\WUHDWPHQWJURXS$GYHUVHGUXJUHDFWLRQVGXULQJWKH
WUHDWPHQWSHULRGLQFOXGHWKRVHZLWKDGDWHRIRQVHWRQWKHGDWHRIVWXG\WUHDWPHQW
LQLWLDWLRQWRRQHGD\DIWHUVWXG\WUHDWPHQWWHUPLQDWLRQ
7KHDGYHUVHGUXJUHDFWLRQVZLOOEHFRGHGXVLQJWKH0HGLFDO'LFWLRQDU\IRU5HJXODWRU\
$FWLYLWLHV0HG'5$DQGZLOOEHUHSRUWHGXVLQJWKHSULPDU\6\VWHP2UJDQ&ODVV62&
DQG3UHIHUUHG7HUP3UHIHUUHG7HUPVZLOOEHVXPPDULVHGZLWKLQWKHSULPDU\62&7KH
UHODWLRQVKLSRISULPDU\62&SUHIHUUHGWHUPVDQGYHUEDWLPWH[WZLOOEHOLVWHG
7KHQXPEHURIVXEMHFWVZLWKRQHRUPRUHHYHQWVRIDQ\W\SHZLOOEHFDOFXODWHG5HVXOWV
ZLOOEHGLVSOD\HGLQWKHRUGHURIGHFUHDVLQJIUHTXHQF\ERWKDFURVVSULPDU\ 62&DQG
ZLWKLQSULPDU\62&
$GYHUVHGUXJUHDFWLRQVGXULQJWKHVWXG\SHULRGZLOODOVREHOLVWHG7KHGHPRJUDSKLF
GHWDLOVHJDJHVH[DQGWKHGHWDLOVRQLQGLYLGXDODGYHUVHHYHQWVZLOOEHLQFOXGHGLQ
WKHVHOLVWLQJV/LVWLQJVZLOOEHVRUWHGZLWKLQVXEMHFWE\WKHDGYHUVHGUXJUHDFWLRQGDWHRI
RQVHW
6LPLODUVXPPDULHVDQGOLVWLQJVZLOOEHSURYLGHGIRUDGYHUVHHYHQWVOHDGLQJWRZLWKGUDZDO
IURPVWXG\
'HDWKVDQG6HULRXV$GYHUVH(YHQWV
'HDWKVDQGVHULRXVDGYHUVHHYHQWVGXULQJWKHVWXG\SHULRGZLOOEHOLVWHG6HULRXVDGYHUVH
HYHQWVGXULQJWKHVWXG\SHULRGZLOODOVREHVXPPDULVHGE\WUHDWPHQWJURXS
$Q\SUHJQDQFLHVVHULRXVDGYHUVHHYHQWVDQGGHDWKVUHSRUWHGGXULQJWKLVVWXG\ZLOODOVR
EHVXPPDULVHGLQFDVHQDUUDWLYHVZULWWHQE\*6.*&63SHUVRQQHO
2WKHUVDIHW\SDUDPHWHUV
$OORWKHUVVDIHW\SDUDPHWHUVZLOOEHOLVWHGDQGVXPPDUL]HG
0RUHVSHFLILFDOO\WKHYLWDOVLJQV%0,SXOVHUDWHV\VWROLFEORRGSUHVVXUHDQGGLDVWROLF
EORRGSUHVVXUHZLOOEHVXPPDUL]HGE\YLVLWDQGWUHDWPHQWJURXS
*HQHWLFUHVHDUFK
,QIRUPDWLRQUHJDUGLQJJHQHWLFUHVHDUFKLVLQFOXGHGLQ$SSHQGL[

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
67

678'<*29(51$1&(&216,'(5$7,216

3RVWLQJRI,QIRUPDWLRQRQ3XEOLFO\$YDLODEOH&OLQLFDO7ULDO
5HJLVWHUV
6WXG\LQIRUPDWLRQIURPWKLVSURWRFROZLOOEHSRVWHGRQSXEOLFO\ DYDLODEOHFOLQLFDOWULDO
UHJLVWHUVEHIRUHHQUROPHQWRIVXEMHFWVEHJLQV

5HJXODWRU\DQG(WKLFDO&RQVLGHUDWLRQV,QFOXGLQJWKH
,QIRUPHG&RQVHQW3URFHVV
3ULRUWRLQLWLDWLRQRIDVWXG\VLWH*6.ZLOOREWDLQIDYRXUDEOHRSLQLRQDSSURYDOIURPWKH
DSSURSULDWHUHJXODWRU\DJHQF\WRFRQGXFWWKHVWXG\LQDFFRUGDQFHZLWK,&+*RRG&OLQLFDO
3UDFWLFH*&3DQGDSSOLFDEOHFRXQWU\VSHFLILFUHJXODWRU\UHTXLUHPHQWV
7KHVWXG\ZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWKDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV
7KHVWXG\ZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWK,&+*&3DOODSSOLFDEOHVXEMHFWSULYDF\
UHTXLUHPHQWVDQGWKHHWKLFDOSULQFLSOHVWKDWDUHRXWOLQHGLQWKH'HFODUDWLRQRI+HOVLQNL
LQFOXGLQJEXWQRWOLPLWHGWR
!
,QVWLWXWLRQDO5HYLHZ%RDUG,5%,QGHSHQGHQW(WKLFV&RPPLWWHH,(& UHYLHZ
&33 LQ )UDQFH ³&RPLWp GH 3URWHFWLRQ GHV 3HUVRQQHV´ DQG IDYRXUDEOH
RSLQLRQDSSURYDORIVWXG\SURWRFRODQGDQ\VXEVHTXHQWDPHQGPHQWV
!
6XEMHFWLQIRUPHGFRQVHQW
!
,QYHVWLJDWRUUHSRUWLQJUHTXLUHPHQWV
*6.ZLOOSURYLGHIXOOGHWDLOVRIWKHDERYHSURFHGXUHVHLWKHUYHUEDOO\LQZULWLQJRUERWK
:ULWWHQLQIRUPHGFRQVHQWPXVWEHREWDLQHGIURPHDFKVXEMHFWSULRUWRSDUWLFLSDWLRQLQWKH
VWXG\

4XDOLW\&RQWURO6WXG\0RQLWRULQJ
,QDFFRUGDQFHZLWKDSSOLFDEOHUHJXODWLRQV*&3DQG*6.SURFHGXUHV*6.PRQLWRUV
ZLOOFRQWDFWWKHVLWHSULRUWRWKHVWDUWRIWKHVWXG\WRUHYLHZZLWKWKHVLWHVWDIIWKHSURWRFRO
VWXG\UHTXLUHPHQWVDQGWKHLUUHVSRQVLELOLWLHVWRVDWLVI\UHJXODWRU\HWKLFDODQG*6.
UHTXLUHPHQWV:KHQUHYLHZLQJGDWDFROOHFWLRQSURFHGXUHVWKHGLVFXVVLRQZLOOLQFOXGH
LGHQWLILFDWLRQDJUHHPHQWDQGGRFXPHQWDWLRQRIGDWDLWHPVIRUZKLFKPHGLFDOUHFRUGVZLOO
VHUYHDVWKHVRXUFHGRFXPHQW
*6.ZLOOPRQLWRUWKHVWXG\WRHQVXUHWKDWWKH
!
'DWDDUHDXWKHQWLFDFFXUDWHDQGFRPSOHWH
!
6DIHW\DQGULJKWVRIVXEMHFWVDUHEHLQJSURWHFWHG
!
6WXG\LVFRQGXFWHGLQDFFRUGDQFHZLWKWKHFXUUHQWO\DSSURYHGSURWRFRODQGDQ\
RWKHUVWXG\DJUHHPHQWV*&3DQGDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
68
7KH,QYHVWLJDWRUDQGWKHKHDGRIWKHPHGLFDOLQVWLWXWLRQZKHUHDSSOLFDEOHDJUHHVWR
DOORZWKHPRQLWRUGLUHFWDFFHVVWRDOOUHOHYDQWGRFXPHQWV

4XDOLW\$VVXUDQFH
7RHQVXUHFRPSOLDQFHZLWK*&3DQGDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV*6.PD\
FRQGXFWDTXDOLW\DVVXUDQFHDVVHVVPHQWDQGRUDXGLWRIWKHVLWHUHFRUGVDQGWKHUHJXODWRU\
DJHQFLHVPD\FRQGXFWDUHJXODWRU\LQVSHFWLRQDWDQ\WLPHGXULQJRUDIWHUFRPSOHWLRQRI
WKHVWXG\,QWKHHYHQWRIDQDVVHVVPHQWDXGLWRULQVSHFWLRQWKHLQYHVWLJDWRUDQG
LQVWLWXWLRQPXVWDJUHHWRJUDQWWKHDGYLVRUVDXGLWRUVDQGLQVSHFWRUVGLUHFWDFFHVVWR
DOOUHOHYDQWGRFXPHQWVDQGWRDOORFDWHWKHLUWLPHDQGWKHWLPHRIWKHLUVWDIIWRGLVFXVVWKH
FRQGXFWRIWKHVWXG\DQ\ILQGLQJVUHOHYDQWLVVXHVDQGWRLPSOHPHQWDQ\FRUUHFWLYHDQGRU
SUHYHQWDWLYHDFWLRQVWRDGGUHVVDQ\ILQGLQJVLVVXHVLGHQWLILHG

6WXG\DQG6LWH&ORVXUH
8SRQFRPSOHWLRQRUWHUPLQDWLRQRIWKHVWXG\WKH*6.PRQLWRUZLOOFRQGXFWVLWHFORVXUH
DFWLYLWLHVZLWKWKH,QYHVWLJDWRURUVLWHVWDIIDVDSSURSULDWHLQDFFRUGDQFHZLWKDSSOLFDEOH
UHJXODWLRQV*&3DQG*6.6WDQGDUG2SHUDWLQJ3URFHGXUHV
*6.UHVHUYHVWKHULJKWWRWHPSRUDULO\VXVSHQGRUWHUPLQDWHWKHVWXG\DWDQ\WLPHIRU
UHDVRQVLQFOXGLQJEXWQRWOLPLWHGWRVDIHW\LVVXHVHWKLFDOLVVXHVRUVHYHUHQRQ
FRPSOLDQFH,I*6.GHWHUPLQHVWKDWVXFKDFWLRQLVUHTXLUHG*6.ZLOOGLVFXVVWKHUHDVRQV
IRUWDNLQJVXFKDFWLRQZLWKWKHLQYHVWLJDWRURUKHDGRIWKHPHGLFDOLQVWLWXWLRQZKHUH
DSSOLFDEOH:KHQIHDVLEOH*6.ZLOOSURYLGHDGYDQFHQRWLFHWRWKH,QYHVWLJDWRURUKHDG
RIWKHPHGLFDOLQVWLWXWLRQRIWKHLPSHQGLQJDFWLRQ
,IDVWXG\LVVXVSHQGHGRUWHUPLQDWHGIRUVDIHW\UHDVRQV*6.ZLOOSURPSWO\LQIRUPDOO
,QYHVWLJDWRUVKHDGVRIWKHPHGLFDOLQVWLWXWLRQVZKHUHDSSOLFDEOHDQGRULQVWLWXWLRQV
FRQGXFWLQJWKHVWXG\*6.ZLOODOVRSURPSWO\LQIRUPWKHUHOHYDQWUHJXODWRU\DXWKRULWLHV
RIWKHVXVSHQVLRQWHUPLQDWLRQDORQJZLWKWKHUHDVRQVIRUVXFKDFWLRQ:KHUHUHTXLUHGE\
DSSOLFDEOHUHJXODWLRQVWKH,QYHVWLJDWRURUKHDGRIWKHPHGLFDOLQVWLWXWLRQPXVWLQIRUPWKH
,(&SURPSWO\DQGSURYLGHWKHUHDVRQVIRUWKHVXVSHQVLRQWHUPLQDWLRQ

5HFRUGV5HWHQWLRQ
)ROORZLQJFORVXUHRIWKHVWXG\WKH,QYHVWLJDWRURUKHDGRIWKHPHGLFDOLQVWLWXWLRQZKHUH
DSSOLFDEOHPXVWPDLQWDLQDOOVLWHVWXG\UHFRUGVH[FHSWIRUWKRVHUHTXLUHGE\ORFDO
UHJXODWLRQVWREHPDLQWDLQHGHOVHZKHUHLQDVDIHDQGVHFXUHORFDWLRQ7KHUHFRUGVPXVW
EHHDVLO\DFFHVVLEOHZKHQQHHGHGHJIRUD*6.DXGLWRUUHJXODWRU\LQVSHFWLRQDQG
PXVWEHDYDLODEOHIRUUHYLHZLQFRQMXQFWLRQZLWKDVVHVVPHQWRIWKHIDFLOLW\VXSSRUWLQJ
V\VWHPVDQGUHOHYDQWVLWHVWDII
:KHUHSHUPLWWHGE\ORFDOODZVUHJXODWLRQVRULQVWLWXWLRQDOSROLF\VRPHRUDOORIWKH
UHFRUGVPD\EHPDLQWDLQHGLQDIRUPDWRWKHUWKDQKDUGFRS\HJPLFURILFKHVFDQQHG
HOHFWURQLFKRZHYHUFDXWLRQPXVWEHH[HUFLVHGEHIRUHVXFKDFWLRQLVWDNHQ7KH
,QYHVWLJDWRUPXVWHQVXUHWKDWDOOUHSURGXFWLRQVDUHOHJLEOHDQGDUHDWUXHDQGDFFXUDWH
FRS\RIWKHRULJLQDO,QDGGLWLRQWKH\PXVWPHHWDFFHVVLELOLW\DQGUHWULHYDOVWDQGDUGV
LQFOXGLQJUHJHQHUDWLRQRIDKDUGFRS\LIUHTXLUHG7KH,QYHVWLJDWRUDQG*6.PXVWDOVR

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
69
HQVXUHWKDWDQDFFHSWDEOHEDFNXSRIWKHUHSURGXFWLRQVH[LVWVDQGWKDWWKHUHLVDQ
DFFHSWDEOHTXDOLW\FRQWUROSURFHGXUHLQSODFHIRUFUHDWLQJWKHUHSURGXFWLRQV
*6.ZLOOLQIRUPWKH,QYHVWLJDWRURIWKHWLPHSHULRGIRUUHWDLQLQJWKHVLWHUHFRUGVLQRUGHU
WRFRPSO\ZLWKDOODSSOLFDEOHUHJXODWRU\ UHTXLUHPHQWV7KHPLQLPXPUHWHQWLRQWLPHZLOO
PHHWWKHVWULFWHVWVWDQGDUGDSSOLFDEOHWRDSDUWLFXODUVLWHDVGLFWDWHGE\ORFDO
ODZVUHJXODWLRQV*6.VWDQGDUGRSHUDWLQJSURFHGXUHVDQGRULQVWLWXWLRQDOUHTXLUHPHQWV
7KH*3,QYHVWLJDWRUPXVWQRWLI\*6.RIDQ\FKDQJHVLQWKHDUFKLYDODUUDQJHPHQWV
LQFOXGLQJEXWQRWOLPLWHGWRDUFKLYDORIUHFRUGVDWDQRIIVLWHIDFLOLW\RUWUDQVIHURI
RZQHUVKLSRIWKHUHFRUGVLQWKHHYHQWWKDWWKH,QYHVWLJDWRULVQRORQJHUDVVRFLDWHGZLWKWKH
VLWH

3URYLVLRQRI6WXG\5HVXOWV WR,QYHVWLJDWRUV3RVWLQJRI
,QIRUPDWLRQRQ3XEOLFDOO\$YDLODEOH&OLQLFDO7ULDOV5HJLVWHUV
DQG3XEOLFDWLRQ
:KHUHUHTXLUHGE\DSSOLFDEOHUHJXODWRU\UHTXLUHPHQWVDQ,QYHVWLJDWRUVLJQDWRU\ZLOOEH
LGHQWLILHGIRUWKHDSSURYDORIWKHFOLQLFDOVWXG\UHSRUW7KH,QYHVWLJDWRUVLJQDWRU\ZLOOEH
SURYLGHGUHDVRQDEOHDFFHVVWRVWDWLVWLFDOWDEOHVILJXUHVDQGUHOHYDQWUHSRUWVDQGZLOOKDYH
WKHRSSRUWXQLW\WRUHYLHZWKHFRPSOHWHVWXG\UHVXOWVDWD*6.VLWHRURWKHUPXWXDOO\
DJUHHDEOHORFDWLRQ
*6.ZLOODOVRSURYLGHWKH,QYHVWLJDWRUZLWKWKHIXOOVXPPDU\RIWKHVWXG\UHVXOWV7KH
,QYHVWLJDWRULVHQFRXUDJHGWRVKDUHWKHVXPPDU\UHVXOWVZLWKWKHVWXG\VXEMHFWVDV
DSSURSULDWH
*6.DLPVWRSRVWDUHVXOWVVXPPDU\WRWKH*6.&OLQLFDO6WXG\5HJLVWHUDQGRWKHU
SXEOLFO\DYDLODEOHUHJLVWHUVQRODWHUWKDQPRQWKVDIWHUWKHODVWVXEMHFW¶VODVWYLVLW/6/9
>WKLVDSSOLHVWRHDFKGDWDDQDO\VLVSKDVHIRUVWXGLHVZLWKPXOWLSOHSKDVHVHJSULPDU\
DQDO\VLVIROORZXSDQDO\VLVHWF@,QDGGLWLRQWKHDLPLVWRVXEPLWDPDQXVFULSWWRDSHHU
UHYLHZHGMRXUQDOIRUSXEOLFDWLRQZLWKLQPRQWKVRI/6/9*6.DOVRDLPVWRSXEOLVK
WKHIXOOVWXG\SURWRFRORQWKH*6.&OLQLFDO6WXG\5HJLVWHUDWWKHWLPHWKHUHVXOWVRIWKH
VWXG\DUHSXEOLVKHGDVDPDQXVFULSWLQWKHVFLHQWLILFOLWHUDWXUH
:KHQPDQXVFULSWSXEOLFDWLRQLQDSHHUUHYLHZHGMRXUQDOLVQRWIHDVLEOHIXUWKHUVWXG\
LQIRUPDWLRQZLOOEHSRVWHGWRWKH*6.&OLQLFDO6WXG\5HJLVWHUWRVXSSOHPHQWWKHUHVXOWV
VXPPDU\
$PDQXVFULSWZLOOEHSURJUHVVHGIRUSXEOLFDWLRQLQWKHVFLHQWLILFOLWHUDWXUHLIWKHUHVXOWV
SURYLGHLPSRUWDQWVFLHQWLILFRUPHGLFDONQRZOHGJH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
70

5()(5(1&(6
%ULWLVK*XLGHOLQHRQWKH0DQDJHPHQWRI$VWKPD%ULWLVK7KRUDFLF6RFLHW\$QDWLRQDO
FOLQLFDOJXLGHOLQHLYLY
&RKHQ-/0DQQ'0:LVQLYHVN\-3+RUQH5/HYHQWKDO+0XVXPHFL6]DER7-+DOP
($$VVHVVLQJWKHYDOLGLW\RIVHOIUHSRUWHGPHGLFDWLRQDGKHUHQFHDPRQJLQQHUFLW\
DVWKPDWLFDGXOWVWKH0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD$QQ$OOHUJ\
$VWKPD,PPXQRO
'RODQ30RGHOLQJYDOXDWLRQVIRU(XUR4ROKHDOWKVWDWHV0HG&DUH

)DQWD&+'UXJ7KHUDS\$VWKPD1HZ(QJO-0HG
*,1$KWWSZZZJLQDVWKPDRUJORFDOXSORDGVILOHV*,1$B5HSRUWB0DUFKSGI
*OD[R6PLWK.OLQH'RFXPHQW1XPEHU 50)OXWLFDVRQH)XURDWH
9LODQWHURO,QYHVWLJDWRU
V%URFKXUH-XQ
*OREDO,QLWLDWLYHIRU$VWKPD*,1$*OREDO6WUDWHJ\IRU$VWKPD0DQDJHPHQWDQG
3UHYHQWLRQ*,1$ZZZJLQDVWKPDRUJ
+DWFKHU5$7UXVVHOO-1HOVRQ$/&DWHV:-U6WHZDUW).RZDO'HGLWRUV
&RQWUDFHSWLYH7HFKQRORJ\WKHGLWLRQ1HZ<RUN$UGHQW0HGLDD7DEOH

+DWFKHU5$7UXVVHOO-1HOVRQ$/&DWHV:-U6WHZDUW).RZDO'HGLWRUV
&RQWUDFHSWLYH7HFKQRORJ\WKHGLWLRQ1HZ<RUN$UGHQW0HGLDE
-DPHV/3HWDO3KDUPDFRNLQHWLFVRI$FHWDPLQRSKHQ3URWHLQ$GGXFWVLQ$GXOWVZLWK
$FHWDPLQRSKHQ2YHUGRVHDQG$FXWH/LYHU)DLOXUH'UXJ0HWDE'LVSRV

-XQLSHU()HWDO'HWHUPLQLQJDPLQLPDOLPSRUWDQWFKDQJHLQDGLVHDVHVSHFLILF4XDOLW\RI
/LIH4XHVWLRQQDLUH-&OLQ(SLGHPLRO-DQ
-XQLSHU()HWDO(YDOXDWLRQRILPSDLUPHQWRIKHDOWKUHODWHGTXDOLW\RIOLIHLQDVWKPD
GHYHORSPHQWRIDTXHVWLRQQDLUHIRUXVHLQFOLQLFDOWULDOV7KRUD[)HE
-XQLSHU()*X\DWW*+:LOOLDPV$*ULIILWK/(0HDVXULQJTXDOLW\RIOLIHLQDVWKPD$P
5HY5HVSLU'LV
-XQLSHU()$VWKPDTXDOLW\RIOLIHTXHVWLRQQDLUHV$4/4$4/46DQG0LQL$4/4
%DFNJURXQGLQIRUPDWLRQDQGLQWHUYLHZLQJWLSV42/7HFKQRORJLHV,QF
.R]PD&0 HWDO'HYHORSPHQWDQG9DOLGDWLRQRID3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH
4XHVWLRQQDLUHIRU,QKDODWLRQ'HYLFHV3$6$347UHDW5HVSLU0HG

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
71
/H*DO)HWDO4XDQWLILFDWLRQRI+HSDWLWLV'HOWD9LUXV51$LQ6HUXPE\&RQVHQVXV
5HDO7LPH3&5,QGLFDWHV'LIIHUHQW3DWWHUQVRI9LURORJLFDO5HVSRQVHWR,QWHUIHURQ
7KHUDS\LQ&KURQLFDOO\,QIHFWHG3DWLHQWV-&OLQ0LFURELRO±
1DWKDQ5$6RUNQHVV&$.RVLQVNL0HWDO'HYHORSPHQWRIWKH$VWKPD&RQWURO7HVW$
VXUYH\IRUDVVHVVLQJDVWKPDFRQWURO-$OOHUJ\&OLQ,PPXQRO-DQXDU\
1,+$VWKPD*XLGHOLQHV6XPPDU\
KWWSZZZQKOELQLKJRYJXLGHOLQHVDVWKPDDVWKVXPPSGI
3HGHUVHQ62
%\UQH3$FRPSDULVRQRIHIILFDF\DQGVDIHW\RILQKDOHGFRUWLFRVWHURLGVLQ
DVWKPD$OOHUJ\
6FKDW]0HWDO7KHPLQLPDOO\LPSRUWDQWGLIIHUHQFHRIWKH$VWKPD&RQWURO7HVW7KH
-RXUQDORIDOOHUJ\DQGFOLQLFDOLPPXQRORJ\
7KH(XUR4RO*URXS7KH(XUR4RO*URXS(XUR4RO DQHZIDFLOLW\IRUWKH
PHDVXUHPHQWRIKHDOWKUHODWHGTXDOLW\RIOLIH+HDOWK3ROLF\

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
72

$33(1',&(6

$SSHQGL[$EEUHYLDWLRQDQG7UDGHPDUNV
$&7
$VWKPD&RQWURO7HVW
$'5
$GYHUVH'UXJ5HDFWLRQ
$(
$GYHUVH(YHQW
$/7
$ODQLQH$PLQRWUDQVIHUDVH
$1&29$
$4/46
$QDO\VLVRI&RYDULDQFH
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH
$67
$VSDUWDWH$PLQRWUDQVIHUDVH
%,'
%8'
&
7ZLFHGDLO\
%XGHVRQLGH
&HOVLXV
&5)
&DVH5HFRUG)RUP
H&5)
(OHFWURQLF&DVH5HFRUG)RUP
&9
&DUGLRYDVFXODU
'1$
'HR[\ULERQXFOHLFDFLG
'3,
'U\3RZGHU,QKDOHU
)3
)OXWLFDVRQH3URSLRQDWH
(&*
(OHFWURFDUGLRJUDP
(3,
(SLGHPLRORJ\
(4'
)
(XUR4RO'
)RUPRWHURO
)'$
)(9
)RRGDQG'UXJ$GPLQLVWUDWLRQ
)RUFHGH[SLUDWRU\YROXPHLQRQHVHFRQG
))
)3
)OXWLFDVRQH)XURDWH
)OXWLFDVRQH3URSLRQDWH
)6+
)ROOLFOH6WLPXODWLQJ+RUPRQH
*&3
*RRG&OLQLFDO3UDFWLFH
*&63
*OREDO&OLQLFDO6DIHW\DQG3KDUPDFRYLJLODQFH
*,1$
*OREDO,QLWLDWLYHIRU$VWKPD
*3
*HQHUDO3UDFWLWLRQHU
*6.
*OD[R6PLWK.OLQH
+3$
+\SRWKDODPLFSLWXLWDU\D[LV
+/
+RGJHV/HKPDQQ
,%
,QYHVWLJDWRUV%URFKXUH
,&6
,QKDOHG&RUWLFRVWHURLG
,(&
,QGHSHQGHQW(WKLFV&RPPLWWHH
,J0
,PPXQRJOREXOLQ0
,J*
,PPXQRJOREXOLQ*
,15
,QWHUQDWLRQDO1RUPDOLVHG5DWLR
,3
,QYHVWLJDWLRQDO3URGXFW
,5%
,QVWLWXWLRQDO5HYLHZ%RDUG
,77
,QWHQWWR7UHDW
,9'
,Q9LWUR'LDJQRVWLF
,57
,QWHUDFWLYH5HVSRQVH7HFKQRORJ\
/$%$
/RQJ$FWLQJ%HWD$JRQLVW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
73
/'+
/DFWDWH'HK\GURJHQDVH
/6/9
0$56$
/DVW6XEMHFW/DVW9LVLW
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHLQ$VWKPD
TXHVWLRQQDLUH
0HG'5$
0FJ
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV
0LFURJUDP
0,
0XOWLSOHLPSXWDWLRQ
0,'
0LQLPDOO\,PSRUWDQW'LIIHUHQFH
0',
0HWHUHG'RVH,QKDOHU
0&,'
0LQLPDOO\&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
PO
0LOOLOLWUH
06'6
0DWHULDO6DIHW\'DWD6KHHW
0050
0L[HGHIIHFWVPRGHOZLWKUHSHDWHGPHDVXUHV
1'3,
1RYHO'U\3RZGHU,QKDOHU
3$6$34
3.
33
352
3DWLHQWV6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH
3KDUPDFRNLQHWLFV
3HUSURWRFRO
3DWLHQW5HSRUWHG2XWFRPHV
SJ
3LFRJUDP
SPRO
3LFRPROHV
4'
2QFH'DLO\
4R/
4XDOLW\RI/LIH
47F
&RUUHFWHG47LQWHUYDO
5$3
5HSRUWLQJ$QDO\VLV3ODQ
5(0/
51$
5HVWULFWHGPD[LPXPOLNHOLKRRG
5LERQXFOHLF$FLG
6
6$(
6DOPHWHURO
6HULRXV$GYHUVH(YHQW
6$3
6WDWLVWLFDO$QDO\VLV3ODQ
6'
62&
623
6WDQGDUGGHYLDWLRQ
6\VWHPRUJDQFODVV
6WDQGDUG2SHUDWLQJ3URFHGXUH
6P3&
6XPPDU\RI3URGXFW&KDUDFWHULVWLFV
6	3
6WDWLVWLFVDQG3URJUDPPLQJ
630
6WXG\3URFHGXUHV0DQXDO
8/1
8SSHU/LPLWRI1RUPDO
9,
9LODQWHURO
:+2
:RUOG+HDOWK2UJDQLVDWLRQ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
74
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
',6.86
$&7
(//,37$
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH
$4/46
5(/9$5
(4'
6(5(7,'(
0$56$TXHVWLRQQDLUH
785%8+$/(5
3$6$34XHVWLRQQDLUH
6\PELFRUW7XUEXKDOHU
;2/$,5

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
75

$SSHQGL[
6WXG\6FKHPDWLF
))9,RSHQ ODEHORUXVXDODVWKPDPDLQWHQDQFHWUHDWPHQW
+=$VWXG\ GHVLJQ
9
'D\
5DQGRPLVDWLRQ
9
'D\
6FUHHQLQJ
ACT , MARS-A, 
AQLQ, EQ-5D, 
Spirometry
$VWKPD WUHDWHG ZLWK
,&60','3,Q 
Relvar 92/22 or 184/22 μg
ICS/LABA DPI on the market
Seretide®, Symbicort®
1-7 days
5
PRQWKV
ACT < 20
V2, errors ass-t:
• Read,
•Demonstrationby HCP,
•1 dose,
•Errors asst & correction
9
:HHN 
9
:HHN 
Possibility to combine 
V1+V2= Day 0
9
3KRQHFDOO
:HHN 
9
3KRQHFDOO
:HHN 
V4, errors ass-t:
•1 dose,
•Errors asst
•Demonstration by 
HCP if critical errors
V6, errors ass-t:
•1 dose,
•Errors asst
•Demonstration by 
HCP if critical errors
ACT, safety
ACT, safety
ACT , MARS-A, 
PASAP, 
Spirometry
ACT , MARS-A, 
AQLQ, EQ-5D
$SKRQHFDOOLVSURYLGHGDW:HHN DQG:HHNLQRUGHUWRFKHFNZKHWKHUWKHVXEMHFW
KDVH[SHULHQFHGDQ\DGYHUVHHYHQWVDQGWKHQWKH,QYHVWLJDWRUFDOOLQJWKHSDWLHQWPXVW
GHWHUPLQHZKHWKHUWKHHYHQWLVUHODWHGWRVWXG\PHGLFDWLRQHLWKHUDUPDQGZKHWKHUWKH
HYHQWLVVHULRXV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
YLVLW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
76

$SSHQGL[4XHVWLRQQDLUHV
$VWKPD&RQWURO7HVW$&7
7KH$&7LVDYDOLGDWHGVHOIDGPLQLVWHUHGTXHVWLRQQDLUHXWLOLVLQJTXHVWLRQVWRDVVHVV
DVWKPDFRQWUROGXULQJWKHSDVWZHHNVRQDSRLQWFDWHJRULFDOVFDOHWR%\
DQVZHULQJDOOTXHVWLRQVDVXEMHFWZLWKDVWKPDFDQREWDLQDVFRUHWKDWPD\UDQJH
EHWZHHQDQGZLWKKLJKHUVFRUHVLQGLFDWLQJEHWWHUFRQWURO$Q$&7VFRUHRIWR
VXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLVXQOLNHO\WREHZHOOFRQWUROOHG$VFRUHRIWR
VXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLVOLNHO\WREHZHOOFRQWUROOHG7KHWRWDOVFRUHLV
FDOFXODWHGDVWKHVXPRIWKHVFRUHVIURPDOOTXHVWLRQV>1DWKDQ 5@7KHPLQLPDOO\
LPSRUWDQWGLIIHUHQFH0,'IRU$&7LV>6FKDW]@
6XEMHFWVZLOOFRPSOHWHWKH$&7DW6FUHHQLQJ9LVLWDW5DQGRPLVDWLRQ9LVLWDW
:HHN9LVLWDQGDW:HHN9LVLWRQVLWH7ZRWHOHSKRQHFDOOVDUHSURYLGHGDW
:HHNDQGDQGVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&7TXHVWLRQQDLUH
DQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
7KH$&7KDVEHHQGHYHORSHGDVDPHDVXUHRIVXEMHFWV¶DVWKPDFRQWUROWKDWFDQEH
TXLFNO\DQGHDVLO\FRPSOHWHGLQFOLQLFDOSUDFWLFH7KHTXHVWLRQVDUHGHVLJQHGWREHVHOI
FRPSOHWHGE\WKHVXEMHFW,WLVUHFRPPHQGHGWKDWWKH$&7EHDGPLQLVWHUHGDWWKHVDPH
WLPHGXULQJHDFKYLVLW7KH$&7VKRXOGEHFRPSOHWHGEHIRUHDQ\SURFHGXUHVDUH
SHUIRUPHGRQWKHVXEMHFWWRDYRLGLQIOXHQFLQJWKHVXEMHFW¶VUHVSRQVH$GHTXDWHWLPH
VKRXOGEHDOORZHGWRFRPSOHWHDOOLWHPVRQWKH$&7
7KHVXEMHFWVKRXOGFRPSOHWHWKHTXHVWLRQQDLUHLQDTXLHWDUHD
7KH,QYHVWLJDWRUVKRXOGDVNWKHVXEMHFWWRFRPSOHWHWKHTXHVWLRQVDVDFFXUDWHO\DV
SRVVLEOH,IWKHVXEMHFWUHTXHVWVKHOSRUFODULILFDWLRQZLWKDQ\RIWKHTXHVWLRQVKHVKHZLOO
EHDVNHGWRUHUHDGWKHLQVWUXFWLRQVDQGJLYHWKHDQVZHUWKDWEHVWUHIOHFWVKRZKHVKHIHOW
RYHUWKHSUHYLRXVZHHNV7KHVXEMHFWVKRXOGEHUHDVVXUHGWKDWWKHUHDUHQRULJKWRU
ZURQJDQVZHUV7KH,QYHVWLJDWRUVKRXOGQRWSURYLGHWKHVXEMHFWZLWKDQ\DQVZHURU
DWWHPSWWRLQWHUSUHWDQ\SRUWLRQRIDTXHVWLRQ
3OHDVHUHIHUWRWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH$4/46
7KH$4/46LVDPRGLILHGYHUVLRQRIWKHRULJLQDO$4/4LQZKLFKDOOWKHDFWLYLW\
TXHVWLRQVDUHJHQHULFDQGLWKDVEHHQYDOLGDWHGIRUXVHLQDVWKPDVXEMHFWVEHWZHHQWKH
DJHVRIDQG7KH$4/4LVDGLVHDVHVSHFLILFVHOIDGPLQLVWHUHGTXDOLW\RIOLIH
TXHVWLRQQDLUHGHYHORSHGWRHYDOXDWHWKHLPSDFWRIDVWKPDWUHDWPHQWVRQWKHTXDOLW\RIOLIH
RIDVWKPDVXIIHUHUVRYHUWKHODVWZHHNV>-XQLSHU@$4/46ZLOOEHPHDVXUHGDW
5DQGRPLVDWLRQDQGDW:HHN(DUO\:LWKGUDZDOYLVLW
7KH$4/4ZKLFKLVDYDLODEOHLQQXPHURXVODQJXDJHVKDVDGHPRQVWUDWHGYDOLGLW\
UHOLDELOLW\DQGUHSURGXFLELOLW\>-XQLSHU-XQLSHU@7KH$4/4FRQWDLQV
LWHPVLQIRXUGRPDLQVDFWLYLW\OLPLWDWLRQLWHPVV\PSWRPVLWHPVHPRWLRQDO
IXQFWLRQLWHPVDQGHQYLURQPHQWDOVWLPXOLLWHPV,QDGGLWLRQWKHLWHPVRIWKH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
77
TXHVWLRQQDLUHDUHDOVRDYHUDJHGWRSURGXFHDQRYHUDOOTXDOLW\RIOLIHVFRUH7KHUHVSRQVH
IRUPDWFRQVLVWVRIDVHYHQSRLQWVFDOHZKHUHDYDOXHRILQGLFDWHV³WRWDOLPSDLUPHQW´DQG
LQGLFDWHV³QRLPSDLUPHQW´$VVXPLQJDVWDWLVWLFDOO\VLJQLILFDQWUHVXOWSWKH
PLQLPDOFOLQLFDOO\PHDQLQJIXOFKDQJHLQRYHUDOOTXDOLW\RIOLIHRULQTXDOLW\RIOLIHIRU
DQ\RIWKHLQGLYLGXDOGRPDLQVLVSRLQWV>-XQLSHU@
,WLVUHFRPPHQGHGWKDWWKH$4/46EHDGPLQLVWHUHGDWWKHVDPHWLPHGXULQJHDFKYLVLW
7KH$4/46PXVWEHDGPLQLVWHUHGEHIRUHLQTXLULQJDERXW$(VDQGDQ\VWXG\
DVVHVVPHQWV$GHTXDWHWLPHVKRXOGEHDOORZHGWRFRPSOHWHDOOLWHPVRQWKH$4/46
1RVWDWHGRULPSOLHGWLPHIRUFRPSOHWLQJWKH$4/46ZLOOEHJLYHQWKRXJKWKHVXUYH\
W\SLFDOO\WDNHVWRPLQXWHVWRFRPSOHWH
6XEMHFWVVKRXOGFRPSOHWHDOOWKHTXHVWLRQVIURPWKH$4/467KH,QYHVWLJDWRUZLOODVN
WKHVXEMHFWWRFRPSOHWHDOOTXHVWLRQVDVDFFXUDWHO\DVSRVVLEOH,IWKHVXEMHFWUHTXHVWVKHOS
RUFODULILFDWLRQRIDQ\TXHVWLRQLQWKH$4/46KHRUVKHVKRXOGEHDVNHGWRUHUHDGWKH
LQVWUXFWLRQVDQGJLYHWKHDQVZHUWKDWEHVWUHIOHFWVKRZKHVKHIHHOVRYHUWKHSUHYLRXVWZR
ZHHNV7KHVXEMHFWVKRXOGEHUHDVVXUHGWKDWWKHUHDUHQRULJKWRUZURQJDQVZHUV7KH
,QYHVWLJDWRUZLOOQRWSURYLGHWKHVXEMHFWZLWKDQ\DQVZHURUDWWHPSWWRLQWHUSUHWDQ\
SRUWLRQRIDTXHVWLRQ3OHDVHUHIHUWRWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV
(XUR4RO4XHVWLRQQDLUH(4'/HYHO
*HQHUDOKHDOWKVWDWXVZLOOEHDVVHVVHGZLWKWKH(XUR4RO(4'/HYHO4XHVWLRQQDLUH
DW5DQGRPLVDWLRQDQG:HHN(DUO\:LWKGUDZDOYLVLW
7KH(4'LVDVWDQGDUGLVHGLQVWUXPHQWIRUXVHDVDPHDVXUHRIKHDOWKVWDWXVWKDWDVNV
VXEMHFWVTXHVWLRQVDERXWWKHLUKHDOWKVWDWXV³WRGD\´>7KH(XUR4RO*URXS@,WLV
GHVLJQHGIRUVHOIFRPSOHWLRQDQGLVFRJQLWLYHO\VLPSOH7KH(4'LVDWZRSDUWVHOI
DVVHVVPHQWTXHVWLRQQDLUH7KHILUVW SDUWFRQVLVWVRIILYHLWHPVFRYHULQJILYHGLPHQVLRQV
PRELOLW\VHOIFDUHXVXDODFWLYLWLHVSDLQGLVFRPIRUWDQGDQ[LHW\GHSUHVVLRQ(DFK
GLPHQVLRQLVPHDVXUHGE\DWKUHHSRLQW/LNHUWVFDOHQRSUREOHPVRPHPRGHUDWH
SUREOHP>V@DQGXQDEOHH[WUHPH SUREOHP>V@
5HVSRQGHQWVDUHDVNHGWRFKRRVHRQHOHYHOWKDWUHIOHFWVWKHLURZQKHDOWKVWDWHWRGD\IRU
HDFKRIWKHILYHGLPHQVLRQV5HVSRQGHQWVFDQWKHQEHFODVVLILHGLQWRRQHRIGLVWLQFW
KHDOWKVWDWHV(4'KHDOWKVWDWHVFDQEHFRQYHUWHGWRDVLQJOHVXPPDU\LQGH[E\
DSSO\LQJDIRUPXODWKDWDWWDFKHVZHLJKWVWRHDFKRIWKHOHYHOVLQHDFKGLPHQVLRQ7KH
IRUPXODLVEDVHGRQWKHYDOXDWLRQRI(4'KHDOWKVWDWHVIURPJHQHUDOSRSXODWLRQ
VDPSOHV>'RODQ@
7KHVHFRQGSDUWRIWKHTXHVWLRQQDLUHFRQVLVWVRIDYHUWLFDOYLVXDODQDORJXHVFDOH(4'
9$6WKDWKDVHQGSRLQWVRI7KHEHVWKHDOWK\RXFDQLPDJLQHDQFKRUHGDWDQG
7KHZRUVWKHDOWK\RXFDQLPDJLQHDQFKRUHGDW5HVSRQGHQWVDUHDVNHGWRLQGLFDWH
KRZWKH\UDWHWKHLUFXUUHQWKHDOWKVWDWHE\GUDZLQJDOLQHIURPWKHER[PDUNHG³\RXUKHDOWK
VWDWXVWRGD\´WRWKHDSSURSULDWHSRLQWRQWKH(4'9$6VFDOH
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH(4'DWWKHVDPHWLPHDWWKH
VSHFLILHG YLVLWV DQG EHIRUH DQ\ VWXG\ SURFHGXUHV 7KH (4' ZLOO EH DGPLQLVWHUHG DW
5DQGRPLVDWLRQ9LVLWDQG:HHN9LVLW(DUO\:LWKGUDZDOYLVLW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
78
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$
5HSRUWHGDGKHUHQFHWRPHGLFDWLRQZLOOEHDVVHVVHGZLWKWKH0HGLFDWLRQ$GKHUHQFH5HSRUW
6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDW9LVLW9LVLWDQG9LVLW(DUO\:LWKGUDZDO
YLVLW
7KH0$56$LVDLWHPTXHVWLRQQDLUHZKHUHPHGLFDWLRQXVHLVUDWHGRQDSRLQW/LNHUW
VFDOHLQGLFDWLQJµDOZD\V¶WRLQGLFDWLQJµQHYHU¶,WKDVEHHQYDOLGDWHGDVDVHOIUHSRUWHG
PHDVXUHRIDGKHUHQFHZLWK,&6IRUVXEMHFWVZLWKDVWKPDDQGLQFOXGHVJHQHULF³,XVHLW
UHJXODUO\HYHU\GD\´DQGOXQJFRQGLWLRQVSHFLILFTXHVWLRQVDERXWPHGLFDWLRQXVH³,RQO\XVH
LWZKHQ,IHHOEUHDWKOHVV´ >&RKHQ@7KHUHLVQRVSHFLILHGWLPHIUDPHRQZKLFK
UHVSRQVHVVKRXOGEHEDVHG
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH0$56$DWWKHVDPHWLPHDWWKH
VSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH0$56KDYHQRVSHFLILHGWLPHIUDPHRQ
ZKLFKUHVSRQVHVVKRXOGEHEDVHG
3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH3$6$34
7KH3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH3$6$34>&0.R]PD@
LVDPXOWLLWHPPHDVXUHRIUHVSLUDWRU\LQKDODWLRQGHYLFHVDWLVIDFWLRQDQGSUHIHUHQFH
GHVLJQHGWREHHDVLO\XQGHUVWRRGDQGDGPLQLVWHUHGWRSDWLHQWVZLWKDVWKPDDQG&23'
3DWLHQWVDWLVIDFWLRQZLWKHDFKGHYLFHDQGGHYLFHSUHIHUHQFHZLOOEHDVVHVVHGDW9LVLW
(DUO\:LWKGUDZDOYLVLW
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH3$6$34DWWKHVDPHWLPHDWWKH
VSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH3$6$34KDVQRVSHFLILHGWLPHIUDPH
RQZKLFKUHVSRQVHVVKRXOGEHEDVHG

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
79

$SSHQGL[/LYHU&KHPLVWU\6WRSSLQJDQG)ROORZXS
&ULWHULD
3KDVH,,,,9OLYHUFKHPLVWU\VWRSSLQJDQGLQFUHDVHGPRQLWRULQJFULWHULD KDYHEHHQ
GHVLJQHGWRDVVXUHVXEMHFWVDIHW\DQGHYDOXDWHOLYHUHYHQWHWLRORJ\LQDOLJQPHQWZLWKWKH
)'$SUHPDUNHWLQJFOLQLFDOOLYHUVDIHW\JXLGDQFH
KWWSZZZIGDJRYGRZQORDGV'UXJV*XLGDQFH&RPSOLDQFH5HJXODWRU\,QIRUPDWLRQ*XLG
DQFHV8&0SGI
3KDVH,,,,9OLYHUFKHPLVWU\VWRSSLQJFULWHULDDQGUHTXLUHGIROORZXSDVVHVVPHQWV
Liver Chemistry Stopping Criteria - Liver Stopping Event
ALT-absolute
$/7∀[8/1
ALT Increase
$/7∀[8/1EXW[8/1SHUVLVWVIRU∀ZHHNV
$/7∀[8/1EXW[8/1SHUVLVWVIRU∀ZHHNV
Bilirubin1, 2
$/7∀[8/1and ELOLUXELQ∀[8/1!GLUHFWELOLUXELQ
INR2
$/7∀[8/1and ,15!LI,15PHDVXUHG
Cannot 
Monitor
$/7∀[8/1EXW[8/1DQGFDQQRWEHPRQLWRUHGZHHNO\IRU∀ZHHNV
$/7∀[8/1EXW[8/1DQGFDQQRWEHPRQLWRUHGZHHNO\IRU∀ZHHNV
Symptomatic3
$/7∀[8/1DVVRFLDWHGZLWKV\PSWRPVQHZRUZRUVHQLQJEHOLHYHGWREH
UHODWHGWROLYHULQMXU\RUK\SHUVHQVLWLYLW\
Required Actions and Follow up Assessments following ANY Liver Stopping Event
Actions
Follow Up Assessments
!
,PPHGLDWHO\GLVFRQWLQXHVWXG\WUHDWPHQW
!
5HSRUWWKHHYHQWWR*6. within 24 hours
!
&RPSOHWHWKHOLYHUHYHQW&5)DQGFRPSOHWH
DQ6$(GDWDFROOHFWLRQWRROLIWKHHYHQWDOVR
PHHWVWKHFULWHULDIRUDQ6$(2
!
3HUIRUPOLYHUHYHQWIROORZXSDVVHVVPHQWV
!
0RQLWRUWKHVXEMHFWXQWLOOLYHUFKHPLVWULHV
UHVROYHVWDELOL]HRUUHWXUQWRZLWKLQEDVHOLQH
VHHMONITORING EHORZ
!
Do not restart/rechallenge VXEMHFWZLWK
VWXG\WUHDWPHQWXQOHVVDOORZHGSHUSURWRFRO
DQG*6.0HGLFDO*RYHUQDQFHDSSURYDOis 
!
9LUDOKHSDWLWLVVHURORJ\
!
2QO\LQWKRVHZLWKXQGHUO\LQJFKURQLF
KHSDWLWLV%DWVWXG\HQWU\LGHQWLILHGE\
SRVLWLYHKHSDWLWLV%VXUIDFHDQWLJHQ
TXDQWLWDWLYHKHSDWLWLV%'1$DQGKHSDWLWLV
GHOWDDQWLERG\
!
%ORRGVDPSOHIRUSKDUPDFRNLQHWLF3.
DQDO\VLVREWDLQHGZLWKLQDIWHUODVWGRVH
!
6HUXPFUHDWLQHSKRVSKRNLQDVH&3.DQG
ODFWDWHGHK\GURJHQDVH/'+
!
)UDFWLRQDWHELOLUXELQLIWRWDO
ELOLUXELQ∀[8/1

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
80
granted UHIHUWR$SSHQGL[
!
,IUHVWDUWUHFKDOOHQJHnot  allowed or not 
grantedSHUPDQHQWO\GLVFRQWLQXHVWXG\
WUHDWPHQWDQGPD\FRQWLQXHVXEMHFWLQWKH
VWXG\IRUDQ\SURWRFROVSHFLILHGIROORZXS
DVVHVVPHQWV
MONITORING:
For bilirubin or INR criteria:
!
5HSHDWOLYHUFKHPLVWULHVLQFOXGH$/7$67
DONDOLQHSKRVSKDWDVHELOLUXELQ DQGSHUIRUP
OLYHUHYHQWIROORZXS DVVHVVPHQWVZLWKLQ24 
hrs
!
0RQLWRUVXEMHFWVWZLFHZHHNO\XQWLOOLYHU
FKHPLVWULHVUHVROYHVWDELOL]HRUUHWXUQWR
ZLWKLQEDVHOLQH
!
$VSHFLDOLVWRUKHSDWRORJ\FRQVXOWDWLRQLV
UHFRPPHQGHG
For All other criteria:
!
5HSHDWOLYHUFKHPLVWULHVLQFOXGH$/7$67
DONDOLQHSKRVSKDWDVHELOLUXELQ DQGSHUIRUP
OLYHUHYHQWIROORZXSDVVHVVPHQWVZLWKLQ24-
72 hrs 
!
0RQLWRUVXEMHFWVZHHNO\XQWLOOLYHUFKHPLVWULHV
UHVROYHVWDELOL]HRUUHWXUQWRZLWKLQEDVHOLQH
!
2EWDLQFRPSOHWHEORRGFRXQWZLWK
GLIIHUHQWLDOWRDVVHVVHRVLQRSKLOLD
!
5HFRUGWKHDSSHDUDQFHRUZRUVHQLQJRI
FOLQLFDOV\PSWRPVRIOLYHULQMXU\RU
K\SHUVHQVLWLYLW\RQWKH$(UHSRUWIRUP
!
5HFRUGXVHRIFRQFRPLWDQWPHGLFDWLRQVRQ
WKHFRQFRPLWDQWPHGLFDWLRQVUHSRUWIRUP
LQFOXGLQJDFHWDPLQRSKHQKHUEDO
UHPHGLHVRWKHURYHUWKHFRXQWHU
PHGLFDWLRQV
!
5HFRUGDOFRKROXVHRQWKHOLYHUHYHQW
DOFRKROLQWDNHFDVHUHSRUWIRUP
For bilirubin or INR criteria:
!
$QWLQXFOHDUDQWLERG\DQWLVPRRWKPXVFOH
DQWLERG\7\SHDQWLOLYHUNLGQH\
PLFURVRPDODQWLERGLHVDQGTXDQWLWDWLYH
WRWDOLPPXQRJOREXOLQ*,J*RUJDPPD
JOREXOLQV
!
6HUXPDFHWDPLQRSKHQDGGXFW+3/&
DVVD\TXDQWLILHVSRWHQWLDODFHWDPLQRSKHQ
FRQWULEXWLRQWROLYHULQMXU\LQVXEMHFWVZLWK
GHILQLWHRUOLNHO\DFHWDPLQRSKHQXVHLQWKH
SUHFHGLQJZHHN>-DPHV@NOTE: 
not required in China
!
/LYHULPDJLQJXOWUDVRXQGPDJQHWLF
UHVRQDQFHRUFRPSXWHULVHGWRPRJUDSK\
DQGRUOLYHUELRSV\WRHYDOXDWHOLYHU
GLVHDVHFRPSOHWH/LYHU,PDJLQJDQGRU
/LYHU%LRSV\&5)IRUPV

6HUXPELOLUXELQIUDFWLRQDWLRQVKRXOGEHSHUIRUPHGLIWHVWLQJLVDYDLODEOH,IVHUXPELOLUXELQIUDFWLRQDWLRQLVQRW
LPPHGLDWHO\DYDLODEOHGLVFRQWLQXHVWXG\WUHDWPHQWIRUWKDWVXEMHFWLI$/7∀[8/1and ELOLUXELQ∀[8/1
$GGLWLRQDOO\LIVHUXPELOLUXELQIUDFWLRQDWLRQWHVWLQJLVXQDYDLODEOHrecord presence of detectable urinary 
bilirubin on dipstickLQGLFDWLQJGLUHFWELOLUXELQHOHYDWLRQVDQGVXJJHVWLQJOLYHULQMXU\

$OOHYHQWVRI$/7∀[8/1and ELOLUXELQ∀[8/1!GLUHFWELOLUXELQRU$/7∀[8/1and ,15!LI,15
PHDVXUHGZKLFKPD\LQGLFDWHVHYHUHOLYHULQMXU\SRVVLEOHµ+\¶V/DZ¶must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis),15PHDVXUHPHQWLVQRWUHTXLUHGDQGWKHWKUHVKROGYDOXHVWDWHG
ZLOOQRWDSSO\WRVXEMHFWVUHFHLYLQJDQWLFRDJXODQWV

1HZRUZRUVHQLQJV\PSWRPVEHOLHYHGWREHUHODWHGWROLYHULQMXU\VXFKDVIDWLJXHQDXVHDYRPLWLQJULJKWXSSHU
TXDGUDQWSDLQRUWHQGHUQHVVRUMDXQGLFHRUEHOLHYHGWREHUHODWHGWRK\SHUVHQVLWLYLW\VXFKDVIHYHUUDVKRU
HRVLQRSKLOLD

+HSDWLWLV$,J0DQWLERG\+HSDWLWLV%VXUIDFHDQWLJHQDQG+HSDWLWLV%&RUH$QWLERG\,J0+HSDWLWLV&51$
&\WRPHJDORYLUXV,J0DQWLERG\(SVWHLQ%DUUYLUDOFDSVLGDQWLJHQ,J0DQWLERG\RULIXQDYDLODEOHREWDLQ
KHWHURSKLOHDQWLERG\RUPRQRVSRWWHVWLQJ+HSDWLWLV(,J0DQWLERG\

,IKHSDWLWLVGHOWDDQWLERG\DVVD\FDQQRWEHSHUIRUPHGLWFDQEHUHSODFHGZLWKD3&5RIKHSDWLWLV'51$YLUXV
ZKHUHQHHGHG>/H*DO@

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
81

3.VDPSOHPD\QRWEHUHTXLUHGIRUVXEMHFWVNQRZQWREHUHFHLYLQJSODFHERRUQRQ*6.FRPSDUDWRUWUHDWPHQWV
5HFRUGWKHGDWHWLPHRIWKH3.EORRGVDPSOHGUDZDQGWKHGDWHWLPHRIWKHODVWGRVHRIVWXG\WUHDWPHQWSULRUWR
EORRGVDPSOHGUDZRQWKH&5),IWKHGDWHRUWLPHRIWKHODVWGRVHLVXQFOHDUSURYLGHWKHVXEMHFW¶VEHVW
DSSUR[LPDWLRQ,IWKHGDWHWLPHRIWKHODVWGRVHFDQQRWEHDSSUR[LPDWHG25D3.VDPSOHFDQQRWEHFROOHFWHGLQ
WKHWLPHSHULRGLQGLFDWHGDERYHGRQRWREWDLQD3.VDPSOH,QVWUXFWLRQVIRUVDPSOHKDQGOLQJDQGVKLSSLQJDUHLQ
WKH650
3KDVH,,,,9OLYHUFKHPLVWU\LQFUHDVHGPRQLWRULQJFULWHULDZLWKFRQWLQXHGWKHUDS\
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event
Criteria
Actions
$/7∀[8/1DQG [8/1and
ELOLUXELQ[8/1without V\PSWRPV
EHOLHYHGWREHUHODWHGWROLYHULQMXU\RU
K\SHUVHQVLWLYLW\and ZKRFDQEH
PRQLWRUHGZHHNO\IRUZHHNV
25
$/7∀[8/1DQG[8/1and
ELOLUXELQ[8/1without V\PSWRPV
EHOLHYHGWREHUHODWHGWROLYHULQMXU\RU
K\SHUVHQVLWLYLW\and ZKRFDQEH
PRQLWRUHGZHHNO\IRUZHHNV
!
1RWLI\WKH*6.PHGLFDOPRQLWRUwithin 24 hours
RIOHDUQLQJRIWKHDEQRUPDOLW\WRGLVFXVVVXEMHFW
VDIHW\
!
6XEMHFWFDQFRQWLQXHVWXG\WUHDWPHQW
!
6XEMHFWPXVWUHWXUQZHHNO\IRUUHSHDWOLYHU
FKHPLVWULHV$/7$67DONDOLQHSKRVSKDWDVH
ELOLUXELQXQWLOWKH\UHVROYHVWDELOLVHRUUHWXUQWR
ZLWKLQEDVHOLQH
!
,IDWDQ\WLPHVXEMHFWPHHWVWKHOLYHUFKHPLVWU\
VWRSSLQJFULWHULDSURFHHGDVGHVFULEHGDERYH
!
,I$/7GHFUHDVHVIURP$/7∀[8/1DQG [8/1
WR[8/1EXW[8/1FRQWLQXHWRPRQLWRUOLYHU
FKHPLVWULHVZHHNO\
!
,IDIWHUZHHNVRIPRQLWRULQJ$/7[8/1DQG
ELOLUXELQ[8/1PRQLWRUVXEMHFWVWZLFHPRQWKO\
XQWLOOLYHUFKHPLVWULHVQRUPDOL]HRUUHWXUQWRZLWKLQ
EDVHOLQH
5HIHUHQFHV
-DPHV/3/HW]LJ/6LPSVRQ30&DSSDUHOOL(5REHUWV':+LQVRQ-$'DYHUQ7-/HH
:03KDUPDFRNLQHWLFVRI$FHWDPLQRSKHQ$GGXFWLQ$GXOWVZLWK$FHWDPLQRSKHQ
2YHUGRVHDQG$FXWH/LYHU)DLOXUH'UXJ0HWDE'LVSRV
/H*DO)*RUGLHQ($IIRODEL'+DQVOLN7$OORXL&'pQ\3*DXOW(4XDQWLILFDWLRQ
RI+HSDWLWLV'HOWD9LUXV51$LQ6HUXPE\&RQVHQVXV5HDO7LPH3&5,QGLFDWHV
'LIIHUHQW3DWWHUQVRI9LURORJLFDO5HVSRQVHWR,QWHUIHURQ7KHUDS\LQ&KURQLFDOO\,QIHFWHG
3DWLHQWV-&OLQ0LFURELRO±

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
82

$SSHQGL['HILQLWLRQRIDQG3URFHGXUHVIRU5HFRUGLQJ
(YDOXDWLQJ)ROORZ8SDQG5HSRUWLQJRI$GYHUVH(YHQWV

'HILQLWLRQRI$GYHUVH(YHQWVDQG$'5V
$GYHUVH(YHQWDQG$'5V'HILQLWLRQ
!
$Q$(LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHLQDSDWLHQWRUFOLQLFDOLQYHVWLJDWLRQ
VXEMHFWWHPSRUDOO\DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOSURGXFWZKHWKHURUQRW
FRQVLGHUHGUHODWHGWRWKHPHGLFLQDOSURGXFW
!
7KHGHILQLWLRQRIDQ$'5LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHLQDSDWLHQWRUFOLQLFDO
LQYHVWLJDWLRQVXEMHFWWHPSRUDOO\DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOSURGXFWIRU
ZKLFKWKHUHLVDUHDVRQDEOHSRVVLELOLW\WKDWWKHXQWRZDUGRFFXUUHQFHLVFDXVDOO\
UHODWHGWRWKHPHGLFLQDOSURGXFW$'5VDUHDVXEVHWRI$(VIRUDJLYHQPHGLFLQDO
SURGXFW
!
127($Q$(FDQWKHUHIRUHEHDQ\ XQIDYRUDEOH DQGXQLQWHQGHGVLJQLQFOXGLQJDQ
DEQRUPDOODERUDWRU\ILQGLQJV\PSWRPRUGLVHDVHQHZRUH[DFHUEDWHGWHPSRUDOO\
DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOSURGXFW
(YHQWVPHHWLQJ $(GHILQLWLRQLQFOXGH
!
$Q\DEQRUPDOODERUDWRU\WHVW UHVXOWVKHPDWRORJ\FOLQLFDOFKHPLVWU\RUXULQDO\VLV
RURWKHUVDIHW\DVVHVVPHQWVHJ(&*VUDGLRORJLFDOVFDQVYLWDOVLJQV
PHDVXUHPHQWVLQFOXGLQJWKRVHWKDWZRUVHQIURPEDVHOLQHDQGIHOWWREHFOLQLFDOO\
VLJQLILFDQWLQWKHPHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKHLQYHVWLJDWRU
!
([DFHUEDWLRQRIDFKURQLFRULQWHUPLWWHQWSUHH[LVWLQJFRQGLWLRQLQFOXGLQJHLWKHUDQ
LQFUHDVHLQIUHTXHQF\DQGRULQWHQVLW\RIWKHFRQGLWLRQ
!
1HZFRQGLWLRQVGHWHFWHGRUGLDJQRVHGDIWHUVWXG\WUHDWPHQWDGPLQLVWUDWLRQHYHQ
WKRXJKLWPD\KDYHEHHQSUHVHQWSULRUWRWKHVWDUWRIWKHVWXG\
!
6LJQVV\PSWRPVRUWKHFOLQLFDOVHTXHODHRIDVXVSHFWHGLQWHUDFWLRQ
!
6LJQVV\PSWRPVRUWKHFOLQLFDOVHTXHODHRIDVXVSHFWHGRYHUGRVHRIHLWKHUVWXG\
WUHDWPHQWRUDFRQFRPLWDQWPHGLFDWLRQRYHUGRVHSHUVHZLOOQRWEHUHSRUWHGDVDQ
$(6$(XQOHVVWKLVLVDQLQWHQWLRQDORYHUGRVHWDNHQZLWKSRVVLEOHVXLFLGDOVHOI
KDUPLQJLQWHQW7KLVVKRXOGEHUHSRUWHGUHJDUGOHVVRIVHTXHODH
!
/DFNRIHIILFDF\RUIDLOXUHRIH[SHFWHGSKDUPDFRORJLFDODFWLRQSHUVHZLOOQRWEH
UHSRUWHGDVDQ$(RU6$(+RZHYHUWKHVLJQVDQGV\PSWRPVDQGRUFOLQLFDO
VHTXHODHUHVXOWLQJIURPODFNRIHIILFDF\ZLOOEHUHSRUWHGLIWKH\IXOILOWKHGHILQLWLRQ
RIDQ$(RU6$(

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
83
(YHQWV127 PHHWLQJGHILQLWLRQRIDQ$(LQFOXGH
!
$Q\FOLQLFDOO\VLJQLILFDQWDEQRUPDOODERUDWRU\ILQGLQJVRURWKHUDEQRUPDOVDIHW\
DVVHVVPHQWVZKLFKDUHDVVRFLDWHGZLWKWKHXQGHUO\LQJGLVHDVHXQOHVVMXGJHGE\WKH
LQYHVWLJDWRUWREHPRUHVHYHUHWKDQH[SHFWHGIRUWKHVXEMHFW¶VFRQGLWLRQ
!
7KHGLVHDVHGLVRUGHUEHLQJVWXGLHGRUH[SHFWHGSURJUHVVLRQVLJQVRUV\PSWRPVRI
WKHGLVHDVHGLVRUGHUEHLQJVWXGLHGXQOHVVPRUHVHYHUHWKDQH[SHFWHGIRUWKHVXEMHFW¶V
FRQGLWLRQ
!
0HGLFDORUVXUJLFDOSURFHGXUHHJHQGRVFRS\DSSHQGHFWRP\WKHFRQGLWLRQWKDW
OHDGVWRWKHSURFHGXUHLVDQ$(
!
6LWXDWLRQVZKHUHDQXQWRZDUGPHGLFDORFFXUUHQFHGLGQRWRFFXUVRFLDODQGRU
FRQYHQLHQFHDGPLVVLRQWRDKRVSLWDO
!
$QWLFLSDWHGGD\WRGD\IOXFWXDWLRQVRISUHH[LVWLQJGLVHDVHVRUFRQGLWLRQVSUHVHQW
RUGHWHFWHGDWWKHVWDUWRIWKHVWXG\WKDW GRQRWZRUVHQ

'HILQLWLRQRI6HULRXV$GYHUVH(YHQWV
,IDQHYHQWLVQRWDQ$(SHUGHILQLWLRQDERYHWKHQLWFDQQRWEHDQ6$(HYHQLIVHULRXV
FRQGLWLRQVDUHPHWHJKRVSLWDOL]DWLRQIRUVLJQVV\PSWRPVRIWKHGLVHDVHXQGHUVWXG\
GHDWKGXHWRSURJUHVVLRQ RIGLVHDVHHWF
6HULRXV$GYHUVH(YHQW6$(LVGHILQHGDVDQ\XQWRZDUGPHGLFDORFFXUUHQFHWKDW
DWDQ\GRVH
D 5HVXOWVLQGHDWK
E ,VOLIHWKUHDWHQLQJ
127(
7KHWHUP
OLIHWKUHDWHQLQJ
LQWKHGHILQLWLRQRI
VHULRXV
UHIHUVWRDQHYHQWLQZKLFKWKH
VXEMHFWZDVDWULVNRIGHDWKDWWKHWLPHRIWKHHYHQW,WGRHVQRWUHIHUWRDQHYHQWZKLFK
K\SRWKHWLFDOO\PLJKWKDYHFDXVHGGHDWKLILWZHUHPRUHVHYHUH
F 5HTXLUHVKRVSLWDOL]DWLRQRUSURORQJDWLRQRIH[LVWLQJKRVSLWDOL]DWLRQ
127(
!
,QJHQHUDOKRVSLWDOL]DWLRQVLJQLILHVWKDWWKHVXEMHFWKDVEHHQGHWDLQHGXVXDOO\
LQYROYLQJDWOHDVWDQRYHUQLJKWVWD\DWWKHKRVSLWDORUHPHUJHQF\ZDUGIRU
REVHUYDWLRQDQGRUWUHDWPHQWWKDWZRXOGQRWKDYHEHHQDSSURSULDWHLQWKHSK\VLFLDQ¶V
RIILFHRURXWSDWLHQW VHWWLQJ&RPSOLFDWLRQVWKDWRFFXUGXULQJKRVSLWDOL]DWLRQDUH
$(V,IDFRPSOLFDWLRQSURORQJVKRVSLWDOL]DWLRQRU IXOILOOV DQ\RWKHUVHULRXVFULWHULD
WKHHYHQWLVVHULRXV:KHQLQGRXEWDVWRZKHWKHU³KRVSLWDOL]DWLRQ´RFFXUUHGRUZDV
QHFHVVDU\WKH$(VKRXOGEHFRQVLGHUHGVHULRXV
!
+RVSLWDOL]DWLRQIRUHOHFWLYHWUHDWPHQWRIDSUHH[LVWLQJFRQGLWLRQWKDWGLGQRWZRUVHQ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
84
IURPEDVHOLQHLVQRWFRQVLGHUHGDQ$(
G 5HVXOWVLQGLVDELOLW\LQFDSDFLW\
127(
!
7KHWHUPGLVDELOLW\PHDQVDVXEVWDQWLDOGLVUXSWLRQRIDSHUVRQ¶VDELOLW\WRFRQGXFW
QRUPDOOLIHIXQFWLRQV
!
7KLVGHILQLWLRQLVQRWLQWHQGHGWRLQFOXGHH[SHULHQFHVRIUHODWLYHO\PLQRUPHGLFDO
VLJQLILFDQFHVXFKDVXQFRPSOLFDWHGKHDGDFKHQDXVHDYRPLWLQJ GLDUUKHDLQIOXHQ]D
DQGDFFLGHQWDOWUDXPDHJVSUDLQHGDQNOHZKLFKPD\LQWHUIHUHRU SUHYHQWHYHU\GD\
OLIHIXQFWLRQVEXWGRQRWFRQVWLWXWHDVXEVWDQWLDOGLVUXSWLRQ
H ,VDFRQJHQLWDODQRPDO\ELUWKGHIHFW
I
2WKHUVLWXDWLRQV
!
0HGLFDORUVFLHQWLILFMXGJPHQWVKRXOGEHH[HUFLVHGLQGHFLGLQJZKHWKHUUHSRUWLQJLV
DSSURSULDWHLQRWKHUVLWXDWLRQVVXFKDVLPSRUWDQWPHGLFDOHYHQWVWKDWPD\QRWEH
LPPHGLDWHO\OLIHWKUHDWHQLQJRUUHVXOWLQGHDWKRUKRVSLWDOL]DWLRQEXWPD\MHRSDUGL]H
WKHVXEMHFWRUPD\UHTXLUHPHGLFDORUVXUJLFDOLQWHUYHQWLRQWRSUHYHQWRQHRIWKH
RWKHURXWFRPHVOLVWHGLQWKHDERYHGHILQLWLRQ7KHVHVKRXOGDOVREHFRQVLGHUHG
VHULRXV
!
([DPSOHVRIVXFKHYHQWVDUHLQYDVLYHRUPDOLJQDQWFDQFHUVLQWHQVLYHWUHDWPHQWLQDQ
HPHUJHQF\URRPRUDWKRPHIRUDOOHUJLFEURQFKRVSDVPEORRGG\VFUDVLDVRU
FRQYXOVLRQVWKDWGRQRWUHVXOWLQKRVSLWDOL]DWLRQ RUGHYHORSPHQWRIGUXJGHSHQGHQF\
RUGUXJDEXVH
J ,VDVVRFLDWHGZLWKOLYHULQMXU\DQG LPSDLUHGOLYHUIXQFWLRQGHILQHGDV
!
$/7∀[8/1DQGWRWDOELOLUXELQ ∀[8/1!GLUHFWRU
!
$/7∀[8/1DQG,15 !
6HUXPELOLUXELQIUDFWLRQDWLRQVKRXOGEHSHUIRUPHGLIWHVWLQJLVDYDLODEOHLIXQDYDLODEOH
PHDVXUHXULQDU\ELOLUXELQYLDGLSVWLFN,IIUDFWLRQDWLRQLVXQDYDLODEOHDQG$/7∀[8/1
DQGWRWDOELOLUXELQ∀[8/1WKHQWKHHYHQWLVVWLOOWREHUHSRUWHGDVDQ6$(
,15WHVWLQJQRWUHTXLUHGSHUSURWRFRODQGWKHWKUHVKROGYDOXHGRHVQRWDSSO\WR
VXEMHFWVUHFHLYLQJDQWLFRDJXODQWV,I,15PHDVXUHPHQWLVREWDLQHGWKHYDOXHLVWREH
UHFRUGHGRQWKH6$(IRUP
!
5HIHUWR$SSHQGL[ IRUWKHUHTXLUHGOLYHUFKHPLVWU\IROORZXS LQVWUXFWLRQV

'HILQLWLRQRI&DUGLRYDVFXODU(YHQWV
&DUGLRYDVFXODU(YHQWV&9'HILQLWLRQ
,QYHVWLJDWRUVZLOOEHUHTXLUHGWRILOORXWWKHVSHFLILF&9HYHQWSDJHRIWKH&5)IRUWKH
IROORZLQJ$(VDQG6$(V

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
85
!
0\RFDUGLDOLQIDUFWLRQXQVWDEOHDQJLQD
!
&RQJHVWLYHKHDUWIDLOXUH
!
$UUK\WKPLDV
!
9DOYXORSDWK\
!
3XOPRQDU\K\SHUWHQVLRQ
!
&HUHEURYDVFXODUHYHQWVVWURNHDQGWUDQVLHQWLVFKHPLFDWWDFN
!
3HULSKHUDODUWHULDOWKURPERHPEROLVP
!
'HHSYHQRXVWKURPERVLVSXOPRQDU\HPEROLVP
!
5HYDVFXODUL]DWLRQ

5HFRUGLQJRI$(V$'5VDQG6$(V
$(VDQG6$(5HFRUGLQJ
!
:KHQDQ$($'5V6$(RFFXUVLWLVWKHUHVSRQVLELOLW\RIWKHLQYHVWLJDWRUWR
UHYLHZDOOGRFXPHQWDWLRQHJKRVSLWDOSURJUHVVQRWHVODERUDWRU\DQGGLDJQRVWLFV
UHSRUWVUHODWLYHWRWKHHYHQW
!
7KHLQYHVWLJDWRUZLOOWKHQUHFRUGDOOUHOHYDQWLQIRUPDWLRQUHJDUGLQJDQ$($'5V
6$(LQWKH&5)
!
,WLVQRW DFFHSWDEOHIRUWKHLQYHVWLJDWRUWRVHQGSKRWRFRSLHVRIWKHVXEMHFW¶VPHGLFDO
UHFRUGVWR*6.LQOLHXRIFRPSOHWLRQRIWKH*6.$($'5V6$(&5)SDJH
!
7KHUHPD\EHLQVWDQFHVZKHQFRSLHVRIPHGLFDOUHFRUGVIRUFHUWDLQFDVHVDUH
UHTXHVWHGE\*6.,QWKLVLQVWDQFHDOOVXEMHFWLGHQWLILHUVZLWKWKHH[FHSWLRQRIWKH
VXEMHFWQXPEHUZLOOEHEOLQGHGRQWKHFRSLHVRIWKHPHGLFDOUHFRUGVSULRUWR
VXEPLVVLRQRIWR*6.
!
7KHLQYHVWLJDWRUZLOODWWHPSWWRHVWDEOLVKDGLDJQRVLVRIWKHHYHQWEDVHGRQVLJQV
V\PSWRPVDQGRURWKHUFOLQLFDOLQIRUPDWLRQ,QVXFKFDVHVWKHGLDJQRVLVZLOOEH
GRFXPHQWHGDVWKH$($'5V6$(DQGQRWWKHLQGLYLGXDOVLJQVV\PSWRPV
!
6XEMHFWFRPSOHWHG9DOXH(YLGHQFHDQG2XWFRPHVTXHVWLRQQDLUHVDQGWKHFROOHFWLRQ
RI$($'5VGDWDDUHLQGHSHQGHQWFRPSRQHQWVRIWKHVWXG\
!
5HVSRQVHVWRHDFKTXHVWLRQLQWKH9DOXH(YLGHQFHDQG2XWFRPHVTXHVWLRQQDLUHZLOO
EHWUHDWHGLQDFFRUGDQFHZLWKVWDQGDUGVFRULQJDQGVWDWLVWLFDOSURFHGXUHVGHWDLOHGE\
WKHVFDOH¶VGHYHORSHU
!
7KHXVHRIDVLQJOHTXHVWLRQIURPDPXOWLGLPHQVLRQDOKHDOWKVXUYH\WRGHVLJQDWHD
FDXVHHIIHFWUHODWLRQVKLSWRDQ$($'5VLVLQDSSURSULDWH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
86

(YDOXDWLQJ$(V$'5VDQG6$(V
$VVHVVPHQWRI,QWHQVLW\
7KHLQYHVWLJDWRUZLOOPDNHDQDVVHVVPHQWRILQWHQVLW\IRUHDFK$($'5VDQG6$(
UHSRUWHGGXULQJWKHVWXG\DQGZLOODVVLJQLWWRRQHRIWKHIROORZLQJFDWHJRULHV
!
0LOG$QHYHQWWKDWLVHDVLO\WROHUDWHGE\WKHVXEMHFWFDXVLQJPLQLPDOGLVFRPIRUW
DQGQRWLQWHUIHULQJZLWKHYHU\GD\DFWLYLWLHV
!
0RGHUDWH$QHYHQWWKDWLVVXIILFLHQWO\GLVFRPIRUWLQJWRLQWHUIHUHZLWKQRUPDO
HYHU\GD\DFWLYLWLHV
!
6HYHUH$QHYHQWWKDWSUHYHQWVQRUPDOHYHU\GD\DFWLYLWLHV DQ$($'5VWKDWLV
DVVHVVHGDVVHYHUHZLOOQRWEHFRQIXVHGZLWKDQ6$(6HYHULW\LVDFDWHJRU\XWLOL]HG
IRUUDWLQJWKHLQWHQVLW\RIDQHYHQWDQGERWK$(V$'5VDQG6$(VFDQEHDVVHVVHG
DVVHYHUH
!
$QHYHQWLVGHILQHGDVµVHULRXV¶ZKHQLWPHHWVDWOHDVWRQHRIWKHSUHGHILQHG
RXWFRPHVDVGHVFULEHGLQWKHGHILQLWLRQRIDQ6$(
$VVHVVPHQWRI&DXVDOLW\
!
7KHLQYHVWLJDWRULVREOLJDWHGWRDVVHVVWKHUHODWLRQVKLSEHWZHHQVWXG\WUHDWPHQWDQG
WKHRFFXUUHQFHRIHDFK$(6$(
!
$UHDVRQDEOHSRVVLELOLW\LVPHDQWWRFRQYH\WKDWWKHUHDUHIDFWVHYLGHQFHRU
DUJXPHQWVWRVXJJHVWDFDXVDOUHODWLRQVKLSUDWKHUWKDQDUHODWLRQVKLSFDQQRWEHUXOHG
RXW
!
7KHLQYHVWLJDWRUZLOOXVHFOLQLFDOMXGJPHQWWRGHWHUPLQHWKHUHODWLRQVKLS
!
$OWHUQDWLYHFDXVHVVXFKDVQDWXUDOKLVWRU\RIWKHXQGHUO\LQJGLVHDVHVFRQFRPLWDQW
WKHUDS\RWKHUULVNIDFWRUVDQGWKHWHPSRUDOUHODWLRQVKLSRIWKHHYHQWWRWKHVWXG\
WUHDWPHQWZLOOEHFRQVLGHUHGDQGLQYHVWLJDWHG
!
7KHLQYHVWLJDWRUZLOODOVRFRQVXOWWKH,QYHVWLJDWRU%URFKXUH,%DQGRU3URGXFW
,QIRUPDWLRQIRUPDUNHWHGSURGXFWVLQWKHGHWHUPLQDWLRQRIKLVKHUDVVHVVPHQW
!
)RUHDFK$(6$(WKHLQYHVWLJDWRUPXVW GRFXPHQWLQWKHPHGLFDOQRWHVWKDWKHVKH
KDVUHYLHZHGWKH$(6$(DQGKDVSURYLGHGDQDVVHVVPHQWRIFDXVDOLW\
!
7KHUHPD\EHVLWXDWLRQVZKHQDQ6$(KDVRFFXUUHGDQGWKHLQYHVWLJDWRUKDVPLQLPDO
LQIRUPDWLRQWRLQFOXGHLQWKHLQLWLDOUHSRUWWR*6.+RZHYHULWLVYHU\LPSRUWDQW
WKDWWKHLQYHVWLJDWRUDOZD\VPDNHDQDVVHVVPHQWRIFDXVDOLW\IRUHYHU\HYHQW
SULRUWRWKHLQLWLDOWUDQVPLVVLRQRIWKH6$(GDWDWR*6.
!
7KHLQYHVWLJDWRUPD\FKDQJHKLVKHURSLQLRQRIFDXVDOLW\LQOLJKWRIIROORZXS
LQIRUPDWLRQDPHQGLQJWKH6$(GDWDFROOHFWLRQWRRODFFRUGLQJO\
!
7KHFDXVDOLW\DVVHVVPHQWLVRQHRIWKHFULWHULDXVHGZKHQGHWHUPLQLQJUHJXODWRU\
UHSRUWLQJUHTXLUHPHQWV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
87
)ROORZXSRI$(VDQG6$(V
!
7KHLQYHVWLJDWRULVREOLJDWHGWRSHUIRUPRUDUUDQJHIRUWKHFRQGXFWRIVXSSOHPHQWDO
PHDVXUHPHQWVDQGRUHYDOXDWLRQVDVPD\EHLQGLFDWHGRUDVUHTXHVWHGE\*6.WR
HOXFLGDWHDVIXOO\DVSRVVLEOHWKHQDWXUHDQGRUFDXVDOLW\RIWKH$(RU6$(
!
7KHLQYHVWLJDWRULVREOLJDWHGWRDVVLVW7KLVPD\LQFOXGHDGGLWLRQDOODERUDWRU\WHVWV
RULQYHVWLJDWLRQVKLVWRSDWKRORJLFDOH[DPLQDWLRQVRUFRQVXOWDWLRQZLWKRWKHUKHDOWK
FDUHSURIHVVLRQDOV
!
,IDVXEMHFWGLHVGXULQJSDUWLFLSDWLRQLQWKHVWXG\RUGXULQJDUHFRJQL]HGIROORZXS
SHULRGWKHLQYHVWLJDWRUZLOOSURYLGH*6.ZLWKDFRS\RIDQ\SRVWPRUWHPILQGLQJV
LQFOXGLQJKLVWRSDWKRORJ\
!
1HZRUXSGDWHGLQIRUPDWLRQZLOOEHUHFRUGHGLQWKHRULJLQDOO\FRPSOHWHG&5)
!
7KHLQYHVWLJDWRUZLOOVXEPLWDQ\XSGDWHG6$(GDWDWR*6.ZLWKLQWKHGHVLJQDWHG
UHSRUWLQJWLPHIUDPHV

5HSRUWLQJRI6$(VWR*6.
6$(UHSRUWLQJWR*6.YLDHOHFWURQLFGDWDFROOHFWLRQWRRO
!
3ULPDU\PHFKDQLVPIRUUHSRUWLQJ6$(VWR*6.ZLOOEHWKHHOHFWURQLFGDWDFROOHFWLRQ
WRRO
!
,IWKHHOHFWURQLFV\VWHPLVXQDYDLODEOHIRUJUHDWHUWKDQKRXUVWKHVLWHZLOOXVHWKH
SDSHU6$(GDWDFROOHFWLRQWRRODQGID[LWWRWKH6$(FRRUGLQDWRU
!
6LWHZLOOHQWHUWKHVHULRXVDGYHUVHHYHQWGDWDLQWRWKHHOHFWURQLFV\VWHPDVVRRQDVLW
EHFRPHVDYDLODEOH
!
7KHLQYHVWLJDWRUZLOOEHUHTXLUHGWRFRQILUPUHYLHZRIWKH6$(FDXVDOLW\E\WLFNLQJ
WKHµUHYLHZHG¶ER[DWWKHERWWRPRIWKHH&5)SDJHZLWKLQKRXUVRIVXEPLVVLRQRI
WKH6$(
!
$IWHUWKHVWXG\LVFRPSOHWHGDWDJLYHQVLWHWKHHOHFWURQLFGDWDFROOHFWLRQWRROHJ
,Q)RUPV\VWHPZLOOEHWDNHQRIIOLQHWRSUHYHQWWKHHQWU\RIQHZGDWDRUFKDQJHVWR
H[LVWLQJGDWD
!
,IDVLWHUHFHLYHVDUHSRUWRIDQHZ6$(IURPDVWXG\VXEMHFWRUUHFHLYHVXSGDWHGGDWD
RQDSUHYLRXVO\UHSRUWHG6$(DIWHUWKHHOHFWURQLFGDWDFROOHFWLRQWRROKDVEHHQWDNHQ
RIIOLQHWKHVLWHFDQUHSRUWWKLVLQIRUPDWLRQRQDSDSHU6$(IRUPRUWRWKH 6$(
FRRUGLQDWRUE\WHOHSKRQH
!
&RQWDFWVIRU6$(UHFHLSWFDQEHIRXQGDWWKHEHJLQQLQJRIWKLVSURWRFRORQWKH
6SRQVRU0HGLFDO0RQLWRU&RQWDFW,QIRUPDWLRQSDJH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
88

$SSHQGL[*HQHWLF5HVHDUFK
*HQHWLF5HVHDUFK2EMHFWLYHVDQG$QDO\VHV
7KHREMHFWLYHVRIWKHJHQHWLFUHVHDUFKDUHWRLQYHVWLJDWHWKHUHODWLRQVKLSEHWZHHQJHQHWLF
YDULDQWVDQG
!
5HVSRQVHWRPHGLFLQHLQFOXGLQJDQ\WUHDWPHQWUHJLPHQVXQGHULQYHVWLJDWLRQLQ
WKLVVWXG\RUDQ\FRQFRPLWDQWPHGLFLQHV
!
$VWKPDVXVFHSWLELOLW\VHYHULW\DQGSURJUHVVLRQDQGUHODWHGFRQGLWLRQV
*HQHWLFGDWDPD\EHJHQHUDWHGZKLOHWKHVWXG\LVXQGHUZD\RUIROORZLQJFRPSOHWLRQRI
WKHVWXG\*HQHWLFHYDOXDWLRQVPD\LQFOXGHIRFXVHGFDQGLGDWHJHQHDSSURDFKHVDQGRU
H[DPLQDWLRQRIDODUJHQXPEHURIJHQHWLFYDULDQWVWKURXJKRXWWKHJHQRPHZKROHJHQRPH
DQDO\VHV*HQHWLFDQDO\VHVZLOOXWLOL]HGDWDFROOHFWHGLQWKHVWXG\DQGZLOOEHOLPLWHGWR
XQGHUVWDQGLQJWKHREMHFWLYHVKLJKOLJKWHGDERYH$QDO\VHVPD\EHSHUIRUPHGXVLQJGDWD
IURPPXOWLSOHFOLQLFDOVWXGLHVWRLQYHVWLJDWHWKHVHUHVHDUFKREMHFWLYHV
$SSURSULDWHGHVFULSWLYHDQGRUVWDWLVWLFDODQDO\VLVPHWKRGVZLOOEHXVHG$GHWDLOHG
GHVFULSWLRQRIDQ\SODQQHGDQDO\VHVZLOOEHGRFXPHQWHGLQD5HSRUWLQJDQG$QDO\VLV3ODQ
5$3SULRUWRLQLWLDWLRQRIWKHDQDO\VLV3ODQQHGDQDO\VHVDQGUHVXOWVRIJHQHWLF
LQYHVWLJDWLRQVZLOOEHUHSRUWHGHLWKHUDVSDUWRIWKHFOLQLFDO5$3DQGVWXG\UHSRUWRULQD
VHSDUDWHJHQHWLFV5$3DQGUHSRUWDVDSSURSULDWH
6WXG\3RSXODWLRQ
$Q\VXEMHFWZKRLVHQUROOHGLQWKHVWXG\FDQSDUWLFLSDWHLQJHQHWLFUHVHDUFK$Q\VXEMHFW
ZKRKDVUHFHLYHGDQ DOORJHQHLF ERQHPDUURZWUDQVSODQWPXVWEHH[FOXGHGIURPWKH
JHQHWLFUHVHDUFK
6WXG\$VVHVVPHQWVDQG3URFHGXUHV
$NH\FRPSRQHQWRIVXFFHVVIXOJHQHWLFUHVHDUFKLVWKHFROOHFWLRQRIVDPSOHVGXULQJ
FOLQLFDOVWXGLHV&ROOHFWLRQRIVDPSOHVHYHQZKHQQRDSULRUL K\SRWKHVLVKDVEHHQ
LGHQWLILHGPD\HQDEOHIXWXUHJHQHWLFDQDO\VHVWREHFRQGXFWHGWRKHOSXQGHUVWDQG
YDULDELOLW\LQGLVHDVHDQGPHGLFLQHUHVSRQVH
!
$POVDOLYDVDPSOHZLOOEHWDNHQIRU'HR[\ULERQXFOHLFDFLG'1$H[WUDFWLRQ
$ VDOLYDVDPSOHLVFROOHFWHGDWWKHEDVHOLQHYLVLW9LVLWDIWHUWKHVXEMHFWKDV
EHHQUDQGRPL]HGDQGSURYLGHGLQIRUPHGFRQVHQWIRUJHQHWLFUHVHDUFK,QVWUXFWLRQV
IRUFROOHFWLRQDQGVKLSSLQJRIWKHJHQHWLFVDPSOHDUHGHVFULEHGLQWKHODERUDWRU\
PDQXDO7KH'1$IURPWKHVDOLYDVDPSOHPD\XQGHUJRTXDOLW\FRQWURODQDO\VHVWR
FRQILUPWKHLQWHJULW\RIWKHVDPSOH,IWKHUHDUHFRQFHUQVUHJDUGLQJWKHTXDOLW\RI
WKHVDPSOHWKHQWKHVDPSOHPD\EHGHVWUR\HG7KHVDOLYDVDPSOHLVWDNHQRQD
VLQJOHRFFDVLRQXQOHVVDGXSOLFDWHVDPSOHLVUHTXLUHGGXHWRDQLQDELOLW\WRXWLOL]H
WKHRULJLQDOVDPSOH
7KHJHQHWLFVDPSOHLVODEHOOHGRU³FRGHG´ZLWKWKHVDPHVWXG\VSHFLILFQXPEHUXVHGWR
ODEHORWKHUVDPSOHVDQGGDWDLQWKHVWXG\7KLVQXPEHUFDQEHWUDFHGRUOLQNHGEDFNWRWKH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
89
VXEMHFWE\WKHLQYHVWLJDWRURUVLWHVWDII&RGHGVDPSOHVGRQRWFDUU\SHUVRQDOLGHQWLILHUV
VXFKDVQDPHRUVRFLDOVHFXULW\QXPEHU
6DPSOHVZLOOEHVWRUHGVHFXUHO\DQGPD\EHNHSWIRUXSWR\HDUVDIWHUWKHODVWVXEMHFW
FRPSOHWHVWKHVWXG\RU*6.PD\GHVWUR\WKHVDPSOHVVRRQHU*6.RUWKRVHZRUNLQJ
ZLWK*6.IRUH[DPSOHRWKHUUHVHDUFKHUVZLOORQO\XVHVDPSOHVFROOHFWHGIURPWKHVWXG\
IRUWKHSXUSRVHVWDWHGLQWKLVSURWRFRODQGLQWKHLQIRUPHGFRQVHQWIRUP6DPSOHVPD\EH
XVHGDVSDUWRIWKHGHYHORSPHQWRIDFRPSDQLRQGLDJQRVWLFWRVXSSRUWWKH*6.PHGLFLQDO
SURGXFW
6XEMHFWVFDQUHTXHVWWKHLUVDPSOHWREHGHVWUR\HGDWDQ\WLPH
,QIRUPHG&RQVHQW
6XEMHFWVZKRGRQRWZLVKWRSDUWLFLSDWHLQWKHJHQHWLFUHVHDUFKPD\VWLOOSDUWLFLSDWHLQWKH
VWXG\*HQHWLFLQIRUPHGFRQVHQWPXVWEHREWDLQHGSULRUWRDQ\VDOLYDEHLQJWDNHQ
6XEMHFW:LWKGUDZDOIURP6WXG\
,IDVXEMHFWZKRKDVFRQVHQWHGWRSDUWLFLSDWHLQJHQHWLFUHVHDUFKZLWKGUDZVIURPWKH
FOLQLFDOVWXG\IRUDQ\UHDVRQRWKHUWKDQEHLQJORVWWRIROORZXSWKH VXEMHFWZLOOEHJLYHQD
FKRLFHRIRQHRIWKHIROORZLQJRSWLRQVFRQFHUQLQJWKHJHQHWLFVDPSOHLIDOUHDG\
FROOHFWHG
!
&RQWLQXHWRSDUWLFLSDWHLQWKHJHQHWLFUHVHDUFKLQZKLFKFDVHWKHJHQHWLF'1$
VDPSOHLVUHWDLQHG
!
'LVFRQWLQXHSDUWLFLSDWLRQLQWKHJHQHWLFUHVHDUFKDQGGHVWUR\WKHJHQHWLF'1$
VDPSOH
,IDVXEMHFWZLWKGUDZVFRQVHQWIRUJHQHWLFUHVHDUFKRUUHTXHVWVVDPSOHGHVWUXFWLRQIRUDQ\
UHDVRQWKHLQYHVWLJDWRUPXVWFRPSOHWHWKHDSSURSULDWHGRFXPHQWDWLRQWRUHTXHVWVDPSOH
GHVWUXFWLRQZLWKLQWKHWLPHIUDPHVSHFLILHGE\*6.DQGPDLQWDLQWKHGRFXPHQWDWLRQLQ
WKHVLWHVWXG\UHFRUGV
*HQRW\SHGDWDPD\EHJHQHUDWHGGXULQJWKHVWXG\RUDIWHUFRPSOHWLRQRIWKHVWXG\DQG
PD\EHDQDO\]HGGXULQJWKHVWXG\RUVWRUHGIRUIXWXUHDQDO\VLV
!
,IDVXEMHFWZLWKGUDZVFRQVHQWIRUJHQHWLFUHVHDUFKDQGJHQRW\SHGDWDKDVQRWEHHQ
DQDO\]HGLWZLOOQRWEHDQDO\]HGRUXVHGIRUIXWXUHUHVHDUFK
!
*HQHWLFGDWDWKDWKDVEHHQDQDO\]HGDWWKHWLPHRIZLWKGUDZQFRQVHQWZLOO
FRQWLQXHWREHVWRUHGDQGXVHGDVDSSURSULDWH
6FUHHQDQG%DVHOLQH)DLOXUHV
,IDVDPSOHIRUJHQHWLFUHVHDUFKKDVEHHQFROOHFWHGDQGLWLVGHWHUPLQHGWKDWWKHVXEMHFW
GRHVQRWPHHWWKHHQWU\FULWHULDIRUSDUWLFLSDWLRQLQWKHVWXG\WKHQWKHLQYHVWLJDWRUVKRXOG
LQVWUXFWWKHVXEMHFWWKDWWKHLUJHQHWLFVDPSOHZLOOEHGHVWUR\HG1RIRUPVDUHUHTXLUHGWR
FRPSOHWHWKLVSURFHVVDVLWZLOOEHFRPSOHWHGDVSDUWRIWKHFRQVHQWDQGVDPSOH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
90
UHFRQFLOLDWLRQSURFHVV,QWKLVLQVWDQFHDVDPSOHGHVWUXFWLRQIRUPZLOOQRWEHDYDLODEOHWR
LQFOXGHLQWKHVLWHILOHV
3URYLVLRQRI6WXG\5HVXOWVDQG&RQILGHQWLDOLW\RI6XEMHFW¶V*HQHWLF'DWD
*6.PD\VXPPDUL]HWKHJHQHWLFUHVHDUFKUHVXOWVLQWKHFOLQLFDOVWXG\UHSRUWRU
VHSDUDWHO\DQGPD\SXEOLVKWKHUHVXOWVLQVFLHQWLILFMRXUQDOV
*6.PD\VKDUHJHQHWLFUHVHDUFKGDWDZLWKRWKHUVFLHQWLVWVWRIXUWKHUVFLHQWLILF
XQGHUVWDQGLQJLQDOLJQPHQWZLWKWKHLQIRUPHGFRQVHQW*6.GRHVQRWLQIRUPWKHVXEMHFW
IDPLO\PHPEHUVLQVXUHUVRUHPSOR\HUVRILQGLYLGXDOJHQRW\SLQJUHVXOWVWKDWDUHQRW
NQRZQWREHUHOHYDQWWRWKHVXEMHFW¶VPHGLFDOFDUHDWWKHWLPHRIWKHVWXG\XQOHVV
UHTXLUHGE\ODZ7KLVLVGXHWRWKHIDFWWKDWWKHLQIRUPDWLRQJHQHUDWHGIURPJHQHWLF
VWXGLHVLVJHQHUDOO\SUHOLPLQDU\LQQDWXUHDQGWKHUHIRUHWKHVLJQLILFDQFHDQGVFLHQWLILF
YDOLGLW\RIWKHUHVXOWVDUHXQGHWHUPLQHG)XUWKHUGDWDJHQHUDWHG LQDUHVHDUFKODERUDWRU\
PD\QRWPHHWUHJXODWRU\UHTXLUHPHQWVIRULQFOXVLRQLQFOLQLFDOFDUH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
91

$SSHQGL[&ROOHFWLRQRI3UHJQDQF\,QIRUPDWLRQ
!
,QYHVWLJDWRUZLOOFROOHFWSUHJQDQF\LQIRUPDWLRQRQDQ\IHPDOHVXEMHFWZKREHFRPHV
SUHJQDQWZKLOHSDUWLFLSDWLQJLQWKLVVWXG\
!
,QIRUPDWLRQZLOOEHUHFRUGHGRQWKHDSSURSULDWHIRUPDQGVXEPLWWHGWR*6.ZLWKLQ
ZHHNVRIOHDUQLQJRIDVXEMHFW
VSUHJQDQF\
!
6XEMHFWZLOOEHIROORZHGWRGHWHUPLQHWKHRXWFRPHRIWKHSUHJQDQF\7KH
LQYHVWLJDWRUZLOOFROOHFWIROORZXSLQIRUPDWLRQRQPRWKHUDQGLQIDQWZKLFKZLOOEH
IRUZDUGHGWR*6.*HQHUDOO\IROORZXSZLOOQRWEHUHTXLUHGIRUORQJHUWKDQWR
ZHHNVEH\RQGWKHHVWLPDWHGGHOLYHU\GDWH
!
$Q\WHUPLQDWLRQRISUHJQDQF\ZLOOEHUHSRUWHGUHJDUGOHVVRIIRHWDOVWDWXVSUHVHQFH
RUDEVHQFHRIDQRPDOLHVRULQGLFDWLRQIRUSURFHGXUH
!
:KLOHSUHJQDQF\LWVHOILVQRWFRQVLGHUHGWREHDQ$(RU6$(DQ\SUHJQDQF\
FRPSOLFDWLRQRUHOHFWLYHWHUPLQDWLRQRIDSUHJQDQF\ZLOOEHUHSRUWHGDVDQ$(RU
6$(
!
$VSRQWDQHRXVDERUWLRQLVDOZD\VFRQVLGHUHGWR EHDQ6$(DQGZLOOEHUHSRUWHGDV
VXFK
!
$Q\6$(RFFXUULQJDVDUHVXOWRIDSRVWVWXG\SUHJQDQF\ZKLFKLVFRQVLGHUHG
UHDVRQDEO\UHODWHGWRWKHVWXG\WUHDWPHQWE\WKHLQYHVWLJDWRUZLOOEHUHSRUWHGWR*6.
DVGHVFULEHGLQ$SSHQGL[:KLOHWKHLQYHVWLJDWRULVQRWREOLJDWHGWRDFWLYHO\VHHN
WKLVLQIRUPDWLRQLQIRUPHUVWXG\SDUWLFLSDQWVKHRUVKHPD\OHDUQRIDQ6$(WKURXJK
VSRQWDQHRXVUHSRUWLQJ
$Q\IHPDOHVXEMHFWZKREHFRPHVSUHJQDQWZKLOHSDUWLFLSDWLQJ
!
ZLOOEHZLWKGUDZQIURPWKHVWXG\
!
,QYHVWLJDWRUZLOODWWHPSWWRFROOHFWSUHJQDQF\LQIRUPDWLRQRQDQ\IHPDOHSDUWQHURID
PDOHVWXG\VXEMHFWZKREHFRPHVSUHJQDQWZKLOHSDUWLFLSDWLQJLQWKLVVWXG\7KLV
DSSOLHVRQO\WRVXEMHFWVZKRDUHUDQGRPL]HGWRUHFHLYHVWXG\PHGLFDWLRQ
!
$IWHUREWDLQLQJWKHQHFHVVDU\VLJQHGLQIRUPHGFRQVHQWIURPWKHIHPDOHSDUWQHU
GLUHFWO\WKHLQYHVWLJDWRUZLOOUHFRUGSUHJQDQF\LQIRUPDWLRQRQWKHDSSURSULDWHIRUP
DQGVXEPLWLWWR*6.ZLWKLQZHHNVRIOHDUQLQJRIWKHSDUWQHU¶VSUHJQDQF\
!
3DUWQHUZLOODOVREHIROORZHGWRGHWHUPLQHWKHRXWFRPHRIWKHSUHJQDQF\
,QIRUPDWLRQRQWKHVWDWXVRIWKHPRWKHUDQGFKLOGZLOOEHIRUZDUGHGWR*6.
*HQHUDOO\IROORZXSZLOOEHQRORQJHUWKDQWRZHHNVIROORZLQJWKHHVWLPDWHGGHOLYHU\
GDWH$Q\WHUPLQDWLRQRIWKHSUHJQDQF\ZLOOEHUHSRUWHGUHJDUGOHVVRIIHWDOVWDWXV
SUHVHQFHRUDEVHQFHRIDQRPDOLHVRULQGLFDWLRQIRUSURFHGXUH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
92

$SSHQGL[3URWRFRO&KDQJHV
7KLVSURWRFRODPHQGPHQWKDVEHHQFUHDWHGWRFRUUHFWPLVWDNHVLQWKHZRUGLQJ RIWKH
LQKDOHUHUURUVTXHVWLRQQDLUHV IRUWKH (//,37$ ',6.86 DQG7XUEXKDOHULQKDOHUV
ZKLFKDUH LQFOXGHGLQ6HFWLRQRIWKHSURWRFRO$OOUHIHUHQFHVWRµ7\SH$HUURUV¶DQG
µRYHUDOOHUURUV¶ZLWKLQWKHSURWRFROKDYHEHHQFKDQJHGWRµFULWLFDO¶DQGµQRQFULWLFDO¶
HUURUVUHVSHFWLYHO\IRUFRQVLVWHQF\ZLWKWKHLQKDOHUHUURUVTXHVWLRQQDLUHZRUNVKHHWV
6WRUDJHFRQGLWLRQLQVWUXFWLRQVIRU6HUHWLGHIOXWLFDVRQHSURSLRQDWHVDOPHWHUROLQ6HFWLRQ
KDYHEHHQDPHQGHG 6HFWLRQRIWKHSURWRFROVWDWHVWKDWWKHVWRUDJHFRQGLWLRQVRI
6HUHWLGHIOXWLFDVRQHSURSLRQDWHVDOPHWHUROPXVWEHVWRUHGDWWHPSHUDWXUHVXSWR#&
$WWKHSRLQWDWZKLFKWKHSURWRFROZDVDSSURYHGLWZDVLQWHQGHGWKDW6HUHWLGHFRPPHUFLDO
VWRFNZRXOGEHSURYLGHGIRUXVHLQWKLVVWXG\+RZHYHUGXHWRODEHOOLQJUHTXLUHPHQWV
WKLVZDVQRWSRVVLEOHDQGWKHFOLQLFDOWULDOLPDJHQHHGHGWREHXVHGLQVWHDG$OO6HUHWLGH
IOXWLFDVRQHSURSLRQDWHVDOPHWHURO'3,VVKRXOGEHVWRUHGDWWHPSHUDWXUHVEHWZHHQ
#&
7KH ZRUGLQJIRUWKHUHFRPPHQGHG QXPEHURIVSLURPHWU\HIIRUWVKDVEHHQUHYLVHG
1HZWH[WKDVEHHQLQFOXGHGZLWKUHJDUGVWRLQYHVWLJDWLRQDOSURGXFWPDOIXQFWLRQLQ
6HFWLRQ
7KHVHFRQGDU\PHGLFDOPRQLWRUFRQWDFWLQIRUPDWLRQKDVEHHQUHYLVHGWRLQFOXGHDQHZ
VWXG\SK\VLFLDQ
2WKHUPLQRUFRUUHFWLRQVDQGHGLWVKDYHEHHQPDGH
0HWKRGRI$PHQGPHQW
2ULJLQDODQGDPHQGHGWH[WVDUHVSHFLILHGDVIROORZV
2ULJLQDOWH[WDVZULWWHQLQWKHRULJLQDOSURWRFRO
5HYLVHGWH[WDVZULWWHQLQ$PHQGPHQW1RZLWKUHYLVLRQVLQEROGIRQW
3URWRFROV\QRSVLVIRUVWXG\+=$DQG6HFWLRQ6HFRQGDU\
2EMHFWLYHVDQG(QGSRLQWV
2ULJLQDOWDEOH
Secondary
!
7RDVVHVVHIIHFWRI))9,RQDVWKPD
FRQWUROFRPSDUHGZLWKXVXDO,&6/$%$
IL[HGFRPELQDWLRQDW:HHN9LVLW
!
7RDVVHVV(//,37$LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXV DQG
!
&KDQJHIURPEDVHOLQHLQ$&7VFRUHDW
:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVPDNLQJDWOHDVW
7\SH$HUURUOLNHO\WREHFULWLFDODQG

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
93
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
RYHUDOOHUURUVDW:HHN9LVLWDQG
DW:HHN9LVLWLQGHSHQGHQWO\RI
WKHXVHDW:HHN9LVLW
Other
!
7RDVVHVVHIIHFWRI))9,RQWURXJKSUH
GRVH)(9FRPSDUHGZLWKXVXDO
,&6/$%$IL[HGFRPELQDWLRQDW:HHN
9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQ
UHVSRQVHWRWUHDWPHQWDW:HHN9LVLW
DQG:HHN9LVLW
!
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQDW:HHN9LVLWDQG
:HHN9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQRYHUWKHVWXG\
SHULRG
!
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIHDW:HHN
9LVLW
!
&KDQJHIURPEDVHOLQHLQWURXJKSUH
GRVH)(9DW:HHN9LVLW
!
$&7VFRUHRUSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7DW:HHN
9LVLWDQG:HHN9LVLW1RWH
$SRLQWLQFUHDVHLQ$&7WRWDOVFRUH
ZDVVXJJHVWHGDVWKH0LQLPDO
&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]
@
!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN
9LVLWDQG:HHN9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
!
1XPEHURIVXEMHFWZLWKDWOHDVW
VHYHUHDVWKPDH[DFHUEDWLRQQXPEHU
RIVHYHUHDVWKPDH[DFHUEDWLRQDQG
DQQXDOVHYHUHH[DFHUEDWLRQUDWHRYHU
WKHVWXG\SHULRG
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUHDW:HHN
9LVLW
!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4VWRWDOVFRUHDW:HHN9LVLW

!
$Q LQFUHDVH IURPEDVHOLQHRI LQ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
94
!
7RDVVHVV3DWLHQW6DWLVIDFWLRQDQG
3UHIHUHQFHDVVHVVPHQWZLWKGLIIHUHQW
LQKDOHUV DW:HHN9LVLW
!
7RHYDOXDWHWKH6DIHW\RI))9,
FRPSDUHGZLWKXVXDO,&6/$%$)36
DQG%XG)
$4/4V
HQYLURQPHQWDO
VWLPXOL
GRPDLQVFRUHDW:HHN9LVLW
!
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVH IURP EDVHOLQH RI   LQ
$4/46 ,QGLYLGXDO GRPDLQ VFRUHV DW
:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
!
+HDOWK VWDWXV XVLQJ WKH (XUR4RO
4XHVWLRQQDLUH (4' DW :HHN 
9LVLW
!
6FRUHRI3$6$34XHVWLRQQDLUH3DWLHQW
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN
9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
! )UHTXHQF\ DQG W\SH RI VHULRXV
DGYHUVHHYHQWV
! )UHTXHQF\ DQG W\SH RI QRQVHULRXV
DGYHUVH GUXJ UHDFWLRQV UHODWHG WR
WUHDWPHQW
5HYLVHGWDEOH
Secondary
!
7RDVVHVVHIIHFWRI))9,RQDVWKPD
FRQWUROFRPSDUHGZLWKXVXDO,&6/$%$
IL[HGFRPELQDWLRQDW:HHN9LVLW
!
7RDVVHVV(//,37$LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXV DQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQ$&7VFRUHDW
:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVPDNLQJDWOHDVW
FULWLFDOHUURUDQGQRQFULWLFDOHUURU
DW:HHN9LVLWDQGDW:HHN
9LVLWLQGHSHQGHQWO\RIWKHXVHDW
:HHN9LVLW
Other
!
7RDVVHVVHIIHFWRI))9,RQWURXJKSUH
!
&KDQJHIURPEDVHOLQHLQWURXJKSUH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
95
GRVH)(9FRPSDUHGZLWKXVXDO
,&6/$%$IL[HGFRPELQDWLRQDW:HHN
9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQ
UHVSRQVHWRWUHDWPHQWDW:HHN9LVLW
DQG:HHN 9LVLW
!
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQDW:HHN9LVLWDQG
:HHN9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQRYHUWKHVWXG\
SHULRG
!
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIHDW:HHN
9LVLW
GRVH)(9DW:HHN9LVLW
!
$&7VFRUHRUSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7DW:HHN
9LVLWDQG:HHN9LVLW1RWH
$SRLQWLQFUHDVHLQ$&7WRWDOVFRUH
ZDVVXJJHVWHGDVWKH0LQLPDO
&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]
@
!
$&7VFRUHDW:HHN9LVLW
DQG:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQLQGLYLGXDO
TXHVWLRQVFRUHVIRU$&7DW:HHNV

!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN
9LVLWDQG:HHN9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
!
1XPEHURIVXEMHFWZLWKDWOHDVW
VHYHUHDVWKPDH[DFHUEDWLRQQXPEHU
RIVHYHUHDVWKPDH[DFHUEDWLRQ DQG
DQQXDOVHYHUHH[DFHUEDWLRQUDWHRYHU
WKHVWXG\SHULRG
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUHDW:HHN
9LVLW
!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4VWRWDOVFRUHDW:HHN9LVLW


2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
96
!
7RDVVHVV3DWLHQW6DWLVIDFWLRQDQG
3UHIHUHQFHDVVHVVPHQWZLWKGLIIHUHQW
LQKDOHUV DW:HHN9LVLW
!
7RHYDOXDWHWKH6DIHW\RI))9,
FRPSDUHGZLWKXVXDO,&6/$%$)36
DQG%XG)
!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4V
HQYLURQPHQWDO
VWLPXOL
GRPDLQVFRUHDW:HHN9LVLW
!
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVH IURP EDVHOLQH RI   LQ
$4/46 ,QGLYLGXDO GRPDLQ VFRUHV DW
:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
!
+HDOWK VWDWXV XVLQJ WKH (XUR4RO
4XHVWLRQQDLUH (4' DW :HHN 
9LVLW
!
6FRUHRI3$6$34XHVWLRQQDLUH3DWLHQW
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN
9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
! )UHTXHQF\ DQG W\SH RI VHULRXV
DGYHUVHHYHQWV
! )UHTXHQF\ DQG W\SH RI QRQVHULRXV
DGYHUVH GUXJ UHDFWLRQV UHODWHG WR
WUHDWPHQW
3URWRFROV\QRSVLVIRUVWXG\+=$2YHUDOO'HVLJQ
2ULJLQDOWH[W
,Q DGGLWLRQ HDFK VXEMHFW ZKRVH ))9, (OOLSWD IRU DVWKPD PDLQWHQDQFH WKHUDS\ LV
LQLWLDWHGDW9LVLWZLOOEHDVNHGWRUHDGWKHLQIRUPDWLRQOHDIOHWDQGZLOOEHLQVWUXFWHGE\
WKHLQYHVWLJDWRURQWKHSURSHUXVHRI(OOLSWD(DFKVXEMHFWZKRVHXVXDO,&6/$%$'3,
'LVNXV RU7XUEXKDOHUIRUDVWKPDPDLQWHQDQFHWKHUDS\LVLQLWLDWHGDW9LVLWZLOOIROORZ
WKHVDPHSURFHGXUHUHDGLQJRIWKHLQIRUPDWLRQOHDIOHWGHPRQVWUDWLRQRIWKHSURSHUXVHRI
WKH LQKDOHUV E\ WKH ,QYHVWLJDWRU DQG WKH FRUUHFW GRVLQJ 7KLV ZLOO EH IROORZHG E\ DQ
LQKDODWLRQGHPRQVWUDWLRQE\WKHSDWLHQW$Q\PLVWDNHV7\SH$HUURUVFRUUHVSRQGLQJWR
FULWLFDOHUURUVDQGRYHUDOOHUURUVZLOOEHUHJLVWHUHGE\WKH,QYHVWLJDWRU)RUWKHGHILQLWLRQ
RI7\SH$HUURUVDQGRYHUDOOHUURUVVHH6HFWLRQ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
97
5DQGRPLVDWLRQDWWKLVYLVLWZLOO EHSHUIRUPHGRQDEDVLVWRWKH ))9,IL[HGGRVH
FRPELQDWLRQ GHOLYHUHG YLD (OOLSWD RU WKH LQLWLDWLRQ ZLWK XVXDO ,&6/$%$ LQKDODWLRQ
SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\
$W:HHN 9LVLWDQGDW:HHN9LVLWVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXW
ZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQVHULRXVDGYHUVH
GUXJUHDFWLRQV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJ7\SH$
HUURUVDQGRYHUDOOHUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWDWURXJKSUHGRVH)(9ZLOOEH
DVVHVVHGE\WKH,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.DQGVXEMHFWVZLOODOVR
EHLQWHUYLHZHGDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRU
QRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVR
EHUHPLQGHGDERXWWKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHVZLOOEHFRQGXFWHGDWWKLVYLVLWDQG7\SH$HUURUVDQGRYHUDOOHUURUVZLWK
LQKDOHUZLOOEHUHFRUGHGIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWVXEMHFWVZLOODOVREHLQWHUYLHZHGDERXW
ZKHWKHUWKH\KDGH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJ
UHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKH
VDPHWLPHRIWKHGD\DV9LVLW
5HYLVHGWH[W
,Q DGGLWLRQ HDFK VXEMHFW ZKRVH ))9, (OOLSWD IRU DVWKPD PDLQWHQDQFH WKHUDS\ LV
LQLWLDWHGDW9LVLWZLOOEHDVNHGWRUHDGWKHLQIRUPDWLRQOHDIOHWDQGZLOOEHLQVWUXFWHGE\
WKHLQYHVWLJDWRURQWKHSURSHUXVHRI(OOLSWD(DFKVXEMHFWZKRVHXVXDO,&6/$%$'3,
'LVNXV RU7XUEXKDOHUIRUDVWKPDPDLQWHQDQFHWKHUDS\LVLQLWLDWHGDW9LVLWZLOOIROORZ
WKHVDPHSURFHGXUHUHDGLQJRIWKHLQIRUPDWLRQOHDIOHWGHPRQVWUDWLRQRIWKHSURSHUXVHRI
WKH LQKDOHUV E\ WKH ,QYHVWLJDWRU DQG WKH FRUUHFW GRVLQJ 7KLV ZLOO EH IROORZHG E\ DQ
LQKDODWLRQGHPRQVWUDWLRQE\WKHSDWLHQW$Q\FULWLFDOHUURUGHILQHGDVDQHUURUWKDWLV
PRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJLQKDOHGDQGRUQRQ
FULWLFDOHUURUZLOOEHUHJLVWHUHGE\WKH,QYHVWLJDWRU
5DQGRPLVDWLRQDWWKLV YLVLWZLOO EHSHUIRUPHGRQ D EDVLVWRWKH ))9,IL[HGGRVH
FRPELQDWLRQ GHOLYHUHG YLD (OOLSWD RU WKH LQLWLDWLRQ ZLWK XVXDO ,&6/$%$ LQKDODWLRQ
SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\
$W:HHN 9LVLWDQGDW:HHN9LVLWVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXW
ZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQVHULRXVDGYHUVH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
98
GUXJUHDFWLRQV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWHWKH$&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOG EHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJFULWLFDODQG
QRQFULWLFDO HUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRIVWXG\
GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQ
FDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWDWURXJKSUHGRVH)(9ZLOOEHDVVHVVHG
E\WKH,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.DQGVXEMHFWVZLOODOVREH
LQWHUYLHZHGDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ
±VHULRXVDGYHUVHGUXJUHDFWLRQV)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREH
UHPLQGHGDERXWWKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHVZLOOEHFRQGXFWHGDWWKLVYLVLWDQGFULWLFDODQGQRQFULWLFDOHUURUV ZLWK
LQKDOHUZLOOEHUHFRUGHGIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWVXEMHFWVZLOODOVREHLQWHUYLHZHGDERXW
ZKHWKHUWKH\KDGH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJ
UHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKH
VDPHWLPHRIWKHGD\DV9LVLW
3URWRFROV\QRSVLVIRUVWXG\+=$$QDO\VLV
2ULJLQDOWH[W
7KH SULPDU\ HQGSRLQW LV GHILQHG DV WKH FKDQJH IURP EDVHOLQH LQ WKH $&7 WRWDO VFRUH
DVVHVVHGDW:HHN9LVLW7KHSULPDU\VHWRIDQDO\VLVLVWKH,77VHW
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHWZRVLGHGQRPLQDO
OHYHORIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,
WR,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
5HYLVHGWH[W
7KH SULPDU\ HQGSRLQW LV GHILQHG DV WKH FKDQJH IURP EDVHOLQH LQ WKH $&7 WRWDO VFRUH
DVVHVVHGDW:HHN9LVLW7KHSULPDU\VHWRIDQDO\VLVLVWKH,77VHW
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHWZRVLGHGQRPLQDO
OHYHORIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,
WR,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
(YHQ WKRXJK WKLV VWXG\ LV RSHQODEHO WKH WHDP ZLOO H[SORUH ZD\V WR HQVXUH VWXG\
EOLQG LV PDLQWDLQHG GXULQJ UHYLHZV RI WKH GDWD DQG SUHSURJUDPPLQJ SULRU WR
GDWDEDVHORFN0RUHLQIRUPDWLRQZLOOEHSURYLGHGLQWKH5$3

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
99
6HFWLRQ± 2YHUDOO'HVLJQ6FUHHQLQJUDQGRPLVDWLRQDQGIROORZXS
2ULJLQDOWH[W
$WWKH6FUHHQLQJ9LVLWHOLJLEOHVXEMHFWVZLOOEHFRQVHQWHGWRSDUWLFLSDWHWRWKHWULDODQG
SUHVFULEHGWKHQHFHVVDU\H[DPLQDWLRQV7KHVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWR
WKH$&7$VFUHHQLQJORJZLOOEHSHUIRUPHGDWWKLVYLVLW
$WDIXUWKHU YLVLWLH9'D\RFFXUULQJZLWKLQZHHNDIWHUWKHVFUHHQLQJYLVLW9
VXEMHFWVZKRPHHWDOORIWKH,QFOXVLRQ&ULWHULDQRQHRIWKH([FOXVLRQ&ULWHULDDQGZKR
DFFHSWWRJLYHWKHLUFRQVHQWZLOOEHUDQGRPLVHGLQWKHVWXG\5DQGRPLVDWLRQDWWKLVYLVLW
ZLOOEHRQDEDVLVWRWKH))9,IL[HGGRVHFRPELQDWLRQGHOLYHUHGE\(OOLSWD RUWRWKH
LQLWLDWLRQRI DQ\ XVXDO ,&6/$%$ '3, IRUDVWKPDPDLQWHQDQFHWKHUDS\FKRVHQE\WKH
SK\VLFLDQ 9LVLW  DQG 9LVLW  FDQ EH FRPELQHG LI WKH VXEMHFW GLG QRW WDNH KLV XVXDO
DVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG9LVLWDUHFRPELQHGWKHQWKLV
YLVLWZLOOEH'D\
$W9LVLW5DQGRPLVDWLRQYLVLW'D\EDVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGE\WKH
,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.$WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOG
EHSHUIRUPHGZLWKUHJLVWUDWLRQRIWKHEHVWYDOXH2QWKHPRUQLQJRI9LVLWVXEMHFWVZLOO
QRWWDNHWKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHG
KRXUVEHIRUHEDVHOLQHVSLURPHWU\
,QDGGLWLRQDW9LVLWVXEMHFWVZLOOEHDVNHGWRUHDGWKHZULWWHQ(OOLSWD SDFNDJHLQVHUWLI
UDQGRPLVHG LQWR WKH ))9, DUP RU 'LVNXV RU 7XUEXKDOHU LI UDQGRPLVHG LQ WKH XVXDO
,&6/$%$WKHUDS\DUPDQGZLOOEHLQVWUXFWHGE\WKHLQYHVWLJDWRURQWKHSURSHUXVHRI
LQKDOHUV 7KHQ WKH VXEMHFW ZLOO VHOIDGPLQLVWHU WKHLU ILUVW GRVH RI VWXG\ GUXJ XQGHU
VXSHUYLVLRQRI WKHLQYHVWLJDWRU $Q\PLVWDNHV7\SH$ HUURUV OLNHO\WR EHFULWLFDO DQG
RYHUDOOHUURUV ZLOO EH UHJLVWHUHGE\ WKHWUDLQHG +&3 $IWHU FRPSOHWLQJ WKHSURFHGXUH
VXEMHFWV ZLOO EH LQVWUXFWHG LQ WKH FRUUHFW XVH RI WKH GHYLFH E\ WKH WUDLQHG SK\VLFLDQ LI
QHHGHG7KHUHDIWHUHDFKVXEMHFWUDQGRPLVHGLQWRWKH))9,DUPZLOOEHLQVWUXFWHGWRVHOI
DGPLQLVWHURQHLQKDODWLRQZLWK(OOLSWD LQKDOHUHDFKGD\DWWKHVDPHWLPHRIWKHGD\DWD
WLPHWKDWLVFRQYHQLHQWIRUWKHVXEMHFW6XEMHFWUDQGRPLVHGLQWRXVXDO,&6/$%$WKHUDS\
DUP ZLOO EH LQVWUXFWHG WR VHOIDGPLQLVWHU WKH LQKDODWLRQ ZLWK 'LVNXV RU 7XUEXKDOHU
LQKDOHUWZLFHDGD\
6XEMHFWV ZLOO EH UHFRPPHQGHG WR XVH 6DOEXWDPRO DV QHHGHG WKURXJKRXW WKH VWXG\ IRU
UHOLHIRIWKHLUDVWKPDV\PSWRPV$W9LVLWUDQGRPLVDWLRQ'D\VXEMHFWZLOOEHDVNHG
WRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
$W :HHN  9LVLW  DQG DW :HHN  9LVLW  VXEMHFWV ZLOO EH WHOHSKRQHG E\ WKH
,QYHVWLJDWRU WR HQTXLUH DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ DGYHUVH HYHQWV
RQO\WKHVHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQVZLOOEHUHFRUGHGLQ
H&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRWWRVWXG\
WUHDWPHQW $W WKHVH WHOHSKRQH FDOOV VXEMHFWV ZLOO DOVR EH DVNHG WR FRPSOHWH WKH $&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
100
DQG 3$6$3 TXHVWLRQQDLUHV DQG WKH LQKDOHU XVH ZLOO EH DVVHVVHG E\ UHFRUGLQJ 7\SH $
HUURUVDQGRYHUDOOHUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ3UHGRVHWURXJK)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJWKHVSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPRO
ZLOOEHVWRSSHGKRXUVEHIRUHWKHVSLURPHWU\$WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOGEH
SHUIRUPHG ZLWK UHJLVWUDWLRQ RI WKH EHVW YDOXH $W WKLV YLVLW VXEMHFWV ZLOO DOVR EH
LQWHUYLHZHGE\WKH,QYHVWLJDWRUDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVH
HYHQWV RQO\ WKH VHULRXV DGYHUVH HYHQWV RU QRQ±VHULRXV DGYHUVH GUXJ UHDFWLRQV ZLOO EH
UHFRUGHGLQH&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRW
WRVWXG\WUHDWPHQW)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREHUHPLQGHGDERXW
WKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHV ZLOO EH FRQGXFWHG DW WKLV YLVLW DQG WKH LQKDOHU XVH ZLOO EH DVVHVVHG E\
UHFRUGLQJ 7\SH $ HUURUV DQG RYHUDOO HUURUV IROORZLQJ WKH QH[W SURFHGXUH VHOI
DGPLQLVWUDWLRQ RI RQH GRVH RI VWXG\ GUXJ E\ VXEMHFW HUURUV DVVHVVPHQW E\ WKH
LQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ
6XEMHFWV ZLOO EH LQWHUYLHZHG DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ VHULRXV
DGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWR
PDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKHVDPHWLPHRIWKHGD\DV9LVLW
5HYLVHGWH[W
$WWKH6FUHHQLQJ9LVLWHOLJLEOHVXEMHFWVZLOOEHFRQVHQWHGWRSDUWLFLSDWHWRWKHWULDODQG
SUHVFULEHGWKHQHFHVVDU\H[DPLQDWLRQV7KHVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWR
WKH$&7$VFUHHQLQJORJZLOOEHSHUIRUPHGDWWKLVYLVLW
$WDIXUWKHUYLVLWLH9'D\RFFXUULQJZLWKLQZHHNDIWHUWKHVFUHHQLQJYLVLW9
VXEMHFWVZKRPHHWDOO RIWKH,QFOXVLRQ&ULWHULDQRQHRIWKH([FOXVLRQ&ULWHULDDQGZKR
DFFHSWWRJLYHWKHLUFRQVHQWZLOOEHUDQGRPLVHGLQWKHVWXG\5DQGRPLVDWLRQDWWKLVYLVLW
ZLOOEHRQDEDVLVWRWKH))9,IL[HGGRVHFRPELQDWLRQGHOLYHUHGE\(OOLSWD RUWRWKH
LQLWLDWLRQ RI WKH XVXDO ,&6/$%$ '3, IRU DVWKPD PDLQWHQDQFH WKHUDS\ FKRVHQ E\ WKH
SK\VLFLDQ 9LVLW  DQG 9LVLW  FDQ EH FRPELQHG LI WKH VXEMHFW GLG QRW WDNH KLV XVXDO
DVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG9LVLWDUHFRPELQHGWKHQWKLV
YLVLWZLOOEH'D\
$W9LVLW5DQGRPLVDWLRQYLVLW'D\EDVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGE\WKH
,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6.$WOHDVWWKUHHDVVHVVPHQWVVKRXOGEH
SHUIRUPHGZLWK UHJLVWUDWLRQ RI WKHEHVWYDOXH$W OHDVWWZR RIWKHVSLURPHWU\ HIIRUWV
VKRXOGEHDFFHSWDEOHDQGUHSHDWDEOH2QWKHPRUQLQJRI9LVLWVXEMHFWVZLOOQRWWDNH
WKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHGKRXUV
EHIRUHEDVHOLQHVSLURPHWU\
,QDGGLWLRQDW9LVLWVXEMHFWVZLOOEHDVNHGWRUHDGWKHZULWWHQ(OOLSWD SDFNDJHLQVHUWLI
UDQGRPLVHG LQWR WKH ))9, DUP RU 'LVNXV RU 7XUEXKDOHU LI UDQGRPLVHG LQ WKH XVXDO
,&6/$%$WKHUDS\DUPDQGZLOOEHLQVWUXFWHGE\WKHLQYHVWLJDWRURQWKHSURSHUXVHRI
LQKDOHUV 7KHQ WKH VXEMHFW ZLOO VHOIDGPLQLVWHU WKHLU ILUVW GRVH RI VWXG\ GUXJ XQGHU

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
101
VXSHUYLVLRQRIWKHLQYHVWLJDWRU$Q\ FULWLFDO HUURUGHILQHG DV DQ HUURUWKDW LV PRVW
OLNHO\WRUHVXOWLQQRRURQO\PLQLPDOPHGLFDWLRQEHLQJLQKDOHGRUQRQFULWLFDOHUURU
ZLOOEHUHJLVWHUHGE\WKHWUDLQHG+&3$IWHUFRPSOHWLQJWKHSURFHGXUHVXEMHFWVZLOOEH
LQVWUXFWHGLQWKHFRUUHFWXVHRIWKHGHYLFHE\WKHWUDLQHGSK\VLFLDQLIQHHGHG7KHUHDIWHU
HDFK VXEMHFW UDQGRPLVHG LQWR WKH ))9, DUP ZLOO EH LQVWUXFWHG WR VHOIDGPLQLVWHU RQH
LQKDODWLRQZLWK(OOLSWD LQKDOHUHDFKGD\DWWKHVDPHWLPHRIWKHGD\DWDWLPHWKDWLV
FRQYHQLHQWIRUWKHVXEMHFW6XEMHFWUDQGRPLVHGLQWRXVXDO,&6/$%$WKHUDS\DUPZLOOEH
LQVWUXFWHGWRVHOIDGPLQLVWHUWKHLQKDODWLRQZLWK'LVNXV RU7XUEXKDOHULQKDOHUWZLFHD
GD\
6XEMHFWV ZLOO EH UHFRPPHQGHG WR XVH 6DOEXWDPRO DV QHHGHG WKURXJKRXW WKH VWXG\ IRU
UHOLHIRIWKHLUDVWKPDV\PSWRPV$W9LVLWUDQGRPLVDWLRQ'D\VXEMHFWZLOOEHDVNHG
WRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
$W :HHN  9LVLW  DQG DW :HHN  9LVLW  VXEMHFWV ZLOO EH WHOHSKRQHG E\ WKH
,QYHVWLJDWRU WR HQTXLUH DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ DGYHUVH HYHQWV
RQO\WKHVHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQVZLOOEHUHFRUGHGLQ
H&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRWWRVWXG\
WUHDWPHQW $W WKHVH WHOHSKRQH FDOOV VXEMHFWV ZLOO DOVR EH DVNHG WR FRPSOHWH WKH $&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJFULWLFDODQG
QRQFULWLFDO HUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRIVWXG\
GUXJ HUURUV DVVHVVPHQW E\ WKH LQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVH RILQKDOHULQ
FDVHRIPXOWLSOHHUURUVGHWHFWLRQ3UHGRVHWURXJK)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJWKHVSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPRO
ZLOOEHVWRSSHGKRXUVEHIRUHWKHVSLURPHWU\$WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOGEH
SHUIRUPHG ZLWK UHJLVWUDWLRQ RI WKH EHVW YDOXH $W WKLV YLVLW VXEMHFWV ZLOO DOVR EH
LQWHUYLHZHGE\WKH,QYHVWLJDWRUDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVH
HYHQWV RQO\ WKH VHULRXV DGYHUVH HYHQWV RU QRQ±VHULRXV DGYHUVH GUXJ UHDFWLRQV ZLOO EH
UHFRUGHGLQH&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRW
WRVWXG\WUHDWPHQW)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREHUHPLQGHGDERXW
WKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHV ZLOO EH FRQGXFWHG DW WKLV YLVLW DQG WKH LQKDOHU XVH ZLOO EH DVVHVVHG E\
UHFRUGLQJ FULWLFDO DQG QRQFULWLFDO
HUURUV IROORZLQJ WKH QH[W SURFHGXUH VHOI
DGPLQLVWUDWLRQ RI RQH GRVH RI VWXG\ GUXJ E\ VXEMHFW HUURUV DVVHVVPHQW E\ WKH
LQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ
6XEMHFWV ZLOO EH LQWHUYLHZHG DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ VHULRXV
DGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWR
PDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKHVDPHWLPHRIWKHGD\DV9LVLW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
102
6HFWLRQ± 2YHUDOO'HVLJQ&ROOHFWHGGDWD
2ULJLQDOWH[W
(OLJLEOHVXEMHFWVZLOOFRPSOHWHWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
DW5DQGRPLVDWLRQ9LVLW9LVLW'D\DQGDW9LVLW:HHNRUDWWKH(DUO\
:LWKGUDZDOYLVLW$&7TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRE\WKHVXEMHFWDW6FUHHQLQJ
YLVLW9LVLW:HHNSKRQHFDOORU9LVLWDW:HHN 9LVLWDQG:HHNSKRQH
FDOORU9LVLW0$56$TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRDW:HHN9LVLW
,QKDOHUXVHDVVHVVPHQWZLOOEHSHUIRUPHGDW5DQGRPLVDWLRQ9LVLW9LVLW'D\DW
:HHN9LVLWDQGDW:HHN9LVLW(DUO\:LWKGUDZDOYLVLWE\UHFRUGLQJWKH
7\SH$HUURUVDQGWKHRYHUDOO HUURUV3DWLHQW¶VVDWLVIDFWLRQDQGSUHIHUHQFH3$6$34
ZLOOEHHYDOXDWHGDW:HHN9LVLW
5HYLVHGWH[W
(OLJLEOHVXEMHFWVZLOOFRPSOHWHWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
DW 5DQGRPLVDWLRQ 9LVLW 9LVLW  'D\  DQG DW 9LVLW  :HHN  RU DW WKH (DUO\
:LWKGUDZDOYLVLW$&7TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRE\WKHVXEMHFWDW6FUHHQLQJ
YLVLW9LVLW:HHNSKRQHFDOORU9LVLWDW:HHN9LVLWDQG:HHNSKRQH
FDOORU9LVLW0$56$TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRDW:HHN9LVLW
,QKDOHU XVH DVVHVVPHQW ZLOO EH SHUIRUPHG DW 5DQGRPLVDWLRQ 9LVLW 9LVLW  'D\  DW
:HHN9LVLWDQGDW:HHN9LVLW(DUO\:LWKGUDZDOYLVLWE\UHFRUGLQJWKH
FULWLFDODQGQRQFULWLFDOHUURUV3DWLHQW¶VVDWLVIDFWLRQDQGSUHIHUHQFH3$6$34ZLOOEH
HYDOXDWHGDW:HHN9LVLW
6HFWLRQ± 7\SHDQG1XPEHURI6XEMHFWV
2ULJLQDOWH[W
6XEMHFWV ZLWK GRFXPHQWHG SK\VLFLDQ¶V GLDJQRVLV RI DVWKPD   \HDU XQVDWLVIDFWRULO\
FRQWUROOHG DVWKPD $&7   WUHDWHG E\ ,&6 DORQH DQG LQWHQGHG WR EH WUHDWHG E\
,&6/$%$ PDLQWHQDQFH WKHUDS\ $ VXEMHFW ZLOO EH HOLJLEOH IRU LQFOXVLRQ LQ WKLV VWXG\
RQO\LIHLWKHUDIILOLDWHGWRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDRIVFUHHQIDLOXUHVXEMHFWVZLOOKDYHWREHVFUHHQHGLQWKH VWXG\ZLWK
VXEMHFWVFHQWHU
5HYLVHGWH[W
6XEMHFWV ZLWK GRFXPHQWHG SK\VLFLDQ¶V GLDJQRVLV RI DVWKPD   \HDU XQVDWLVIDFWRULO\
FRQWUROOHG DVWKPD $&7   WUHDWHG E\ ,&6 DORQH DQG LQWHQGHG WR EH WUHDWHG E\
,&6/$%$ PDLQWHQDQFH WKHUDS\ $ VXEMHFW ZLOO EH HOLJLEOH IRU LQFOXVLRQ LQ WKLV VWXG\
RQO\LIHLWKHUDIILOLDWHGWRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
103
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDW OHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDVFUHHQIDLOXUH UDWHDSSUR[LPDWHO\ VXEMHFWVZLOOKDYHWREH
VFUHHQHGLQWKHVWXG\ZLWKVXEMHFWVFHQWHU
6HFWLRQ± 5LVN$VVHVVPHQW
2ULJLQDOWH[W
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
+\SHUVHQVLWLYLW\
7KHUHSRUWHG
K\SHUVHQVLWLYLW\HYHQWVLQ
FOLQLFDOWULDOVZHUHQRW
JHQHUDOO\VHULRXVGLGQRW
OHDGWRGLVFRQWLQXDWLRQLQ
WKHVWXGLHVDQGZHUH
XVXDOO\FRQIRXQGHGE\
HLWKHUWKHVXEMHFW¶VPHGLFDO
FRQGLWLRQVXFKDV&23'
RURWKHUIDFWRUVDWWKHWLPH
RIWKHHYHQW
,QVSRQWDQHRXVGDWD
V\PSWRPVRI
K\SHUVHQVLWLYLW\UDQJHG
IURPPLOGUDVKDQGSUXULWLV
WRVHYHUHJHQHUDOLVHGUDVK
DQGHU\WKHPDDQGVHYHUH
FDVHVLQYROYLQJDQJLRGHPD
RIWKHIDFHODU\Q[DQG
SKDU\Q[
7KHVHHYHQWVZHUHUDUH
6XEMHFWV ZLWK D KLVWRU\ RI
DGYHUVH UHDFWLRQ LQFOXGLQJ
LPPHGLDWH
RU
GHOD\HG
K\SHUVHQVLWLYLW\
WR
DQ\
LQWUDQDVDO
LQKDOHG
RU
V\VWHPLF FRUWLFRVWHURLG DQG
/$%$
WKHUDS\
DQG
WR
FRPSRQHQWV
RI
WKH
LQKDODWLRQ
SRZGHU
HJ
ODFWRVH
PDJQHVLXP
VWHDUDWH
,Q
DGGLWLRQ
VXEMHFWV ZLWK D KLVWRU\ RI
VHYHUH PLON SURWHLQ DOOHUJ\
WKDW LQ WKH RSLQLRQ RI WKH
,QYHVWLJDWRUFRQWUDLQGLFDWHV
WKH VXEMHFW¶V SDUWLFLSDWLRQ
ZLOODOVREHH[FOXGHG

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
104
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
6\VWHPLFHIIHFWVRI
FRUWLFRVWHURLGVDGUHQDO
VXSSUHVVLRQH\HGLVRUGHUV
GHFUHDVHGERQHGHQVLW\DQG
DVVRFLDWHGIUDFWXUHV
$GUHQDOVXSSUHVVLRQLVD
NQRZQFODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
VWXGLHVVKRZHGWKDW))
HIIHFWVDUHFRPSDUDEOHZLWK
RWKHUFRUWLFRVWHURLGV1R
VWXGLHVKDYHVKRZQD
FOLQLFDOO\UHOHYDQWHIIHFWRI
))9,RQWKHK\SRWKDODPLF
SLWXLWDU\D[LV+3$7KLV
LQFOXGHVDIRUPDO+3$
VWXG\+=$XVLQJ
KRXUVHUXPFRUWLVRO
PHDVXUHPHQWVDQGPXOWLSOH
VWXGLHVZLWK&23'DQG
DVWKPDVXEMHFWVZKLFK
PRQLWRUHGXULQDU\FRUWLVRO
'XULQJFOLQLFDO
GHYHORSPHQWQRHYHQWVRI
$GUHQDO6XSSUHVVLRQZHUH
UHSRUWHG
(\HGLVRUGHUVDUHDNQRZQ
FODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
VWXGLHVVKRZHG))DWKLJK
GRVHFRPSDUDEOHWRRWKHU
KLJKGRVHFRUWLFRVWHURLGV,Q
VWXG\+=$))9,
))DQG)3LQVXEMHFWVZLWK
DVWKPD
IRUPDORSKWKDOPLF
DVVHVVPHQWVZHUHFRQGXFWHG
LQFOXGLQJ/2&6,,,
HYDOXDWLRQVIRURFXODU
RSDFLWLHVWKURXJKRXWWKH
VWXG\7KLVVWXG\VKRZHG
QRDSSDUHQWHIIHFWVRQOHQV
RSDFLILFDWLRQFRPSDUHGWR
EDVHOLQH'XULQJVWXGLHVLQ
ERWKVXEMHFWVZLWKDVWKPD
DQG&23'QRDVVRFLDWHG
DIIHFWRQRFXODUGLVRUGHUV
7KHPLWLJDWLRQLQWKLVVWXG\
IRU DOO V\VWHPLF HIIHFWV RI
FRUWLFRVWHURLGV
LV
WKDW
FKURQLF XVHUV RI V\VWHPLF
FRUWLFRVWHURLGVDUHH[FOXGHG
IURP WKLV VWXG\ D VXEMHFW
ZKR LQ WKH RSLQLRQ RI WKH
,QYHVWLJDWRU LV FRQVLGHUHG
WR EH D FKURQLF XVHU RI
V\VWHPLF FRUWLFRVWHURLGV IRU
UHVSLUDWRU\
RU
RWKHU
LQGLFDWLRQV
LI
XQVXUH
GLVFXVV ZLWK WKH PHGLFDO
PRQLWRUSULRUWRVFUHHQLQJ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
105
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
ZDVREVHUYHG
'HFUHDVHGERQHGHQVLW\LVD
GRZQ FODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
GDWDVKRZHGWKDWKLJKGRVH
FRUWLFRVWHURLGHIIHFWVRI))
ZHUHFRPSDUDEOHWRRWKHU
FRQUWLFRVWHURLGV3DWLHQWV
ZLWK$VWKPD,QDQ
LQWHJUDWHGDQDO\VLVRI
VWXGLHVLQDVWKPD
SDWLHQWVWKHLQFLGHQFHRI
IUDFWXUHVZLWK))9,ZDV
 DQGXVXDOO\
DVVRFLDWHGZLWKWUDXPD
5HYLVHGWH[W
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
+\SHUVHQVLWLYLW\
7KHUHSRUWHG
K\SHUVHQVLWLYLW\HYHQWVLQ
FOLQLFDOWULDOVZHUHQRW
JHQHUDOO\VHULRXVGLGQRW
OHDGWRGLVFRQWLQXDWLRQLQ
WKHVWXGLHVDQGZHUH
XVXDOO\FRQIRXQGHGE\
HLWKHUWKHVXEMHFW¶VPHGLFDO
FRQGLWLRQVXFKDV&23'
RURWKHUIDFWRUVDWWKHWLPH
RIWKHHYHQW
,QVSRQWDQHRXVGDWD
V\PSWRPVRI
K\SHUVHQVLWLYLW\UDQJHG
IURPPLOGUDVKDQGSUXULWLV
6XEMHFWV ZLWK D KLVWRU\ RI
DGYHUVH UHDFWLRQ LQFOXGLQJ
LPPHGLDWH
RU
GHOD\HG
K\SHUVHQVLWLYLW\
WR
DQ\
LQWUDQDVDO
LQKDOHG
RU
V\VWHPLF FRUWLFRVWHURLG DQG
/$%$
WKHUDS\
DQG
WR
FRPSRQHQWV
RI
WKH
LQKDODWLRQ
SRZGHU
HJ
ODFWRVH
PDJQHVLXP
VWHDUDWH ZLOO EH H[FOXGHG
,Q DGGLWLRQVXEMHFWVZLWKD
KLVWRU\
RI
VHYHUH
PLON
SURWHLQ DOOHUJ\ WKDW LQ WKH
RSLQLRQ RI WKH ,QYHVWLJDWRU
FRQWUDLQGLFDWHVWKHVXEMHFW¶V

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
106
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
WRVHYHUHJHQHUDOLVHGUDVK
DQGHU\WKHPDDQGVHYHUH
FDVHVLQYROYLQJDQJLRGHPD
RIWKHIDFHODU\Q[DQG
SKDU\Q[
7KHVHHYHQWVZHUHUDUH
SDUWLFLSDWLRQ ZLOO DOVR EH
H[FOXGHG
6\VWHPLFHIIHFWVRI
FRUWLFRVWHURLGVDGUHQDO
VXSSUHVVLRQH\HGLVRUGHUV
GHFUHDVHGERQHGHQVLW\DQG
DVVRFLDWHGIUDFWXUHV
$GUHQDOVXSSUHVVLRQLVD
NQRZQFODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
VWXGLHVVKRZHGWKDW))
HIIHFWVDUHFRPSDUDEOHZLWK
RWKHUFRUWLFRVWHURLGV1R
VWXGLHVKDYHVKRZQD
FOLQLFDOO\UHOHYDQWHIIHFWRI
))9,RQWKHK\SRWKDODPLF
SLWXLWDU\D[LV+3$7KLV
LQFOXGHVDIRUPDO+3$
VWXG\+=$XVLQJ
KRXUVHUXPFRUWLVRO
PHDVXUHPHQWVDQGPXOWLSOH
VWXGLHVZLWK&23'DQG
DVWKPDVXEMHFWVZKLFK
PRQLWRUHGXULQDU\FRUWLVRO
'XULQJFOLQLFDO
GHYHORSPHQWQRHYHQWVRI
$GUHQDO6XSSUHVVLRQZHUH
UHSRUWHG
(\HGLVRUGHUVDUHDNQRZQ
FODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
VWXGLHVVKRZHG))DWKLJK
GRVHFRPSDUDEOHWRRWKHU
KLJKGRVHFRUWLFRVWHURLGV,Q
VWXG\+=$))9,
))DQG)3LQVXEMHFWVZLWK
DVWKPD
IRUPDORSKWKDOPLF
DVVHVVPHQWVZHUHFRQGXFWHG
LQFOXGLQJ/2&6,,,
HYDOXDWLRQVIRURFXODU
7KHPLWLJDWLRQLQWKLVVWXG\
IRU DOO V\VWHPLF HIIHFWV RI
FRUWLFRVWHURLGV
LV
WKDW
FKURQLF XVHUV RI V\VWHPLF
FRUWLFRVWHURLGVDUHH[FOXGHG
IURP WKLV VWXG\ D VXEMHFW
ZKR LQ WKH RSLQLRQ RI WKH
,QYHVWLJDWRU LV FRQVLGHUHG
WR EH D FKURQLF XVHU RI
V\VWHPLF FRUWLFRVWHURLGV IRU
UHVSLUDWRU\
RU
RWKHU
LQGLFDWLRQV
LI
XQVXUH
GLVFXVV ZLWK WKH PHGLFDO
PRQLWRU SULRU WR VFUHHQLQJ
ZLOOEHH[FOXGHG

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
107
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
RSDFLWLHVWKURXJKRXWWKH
VWXG\7KLVVWXG\VKRZHG
QRDSSDUHQWHIIHFWVRQOHQV
RSDFLILFDWLRQFRPSDUHGWR
EDVHOLQH'XULQJVWXGLHVLQ
ERWKVXEMHFWVZLWKDVWKPD
DQG&23'QRDVVRFLDWHG
DIIHFWRQRFXODUGLVRUGHUV
ZDVREVHUYHG
'HFUHDVHGERQHGHQVLW\LVD
NQRZQ FODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDO
GDWDVKRZHGWKDWKLJKGRVH
FRUWLFRVWHURLGHIIHFWVRI))
ZHUHFRPSDUDEOHWRRWKHU
FRQUWLFRVWHURLGV3DWLHQWV
ZLWK$VWKPD,QDQ
LQWHJUDWHGDQDO\VLVRI
VWXGLHVLQDVWKPD
SDWLHQWVWKHLQFLGHQFHRI
IUDFWXUHVZLWK))9,ZDV
 DQGXVXDOO\
DVVRFLDWHGZLWKWUDXPD
6HFWLRQ± 6FUHHQLQJ%DVHOLQH)DLOXUHV
2ULJLQDOWH[W
$WRWDORIVXEMHFWVZLOOEHVFUHHQHGDVVXEMHFWVDUHSODQQHGWREHUDQGRPLVHGDQG
RIVFUHHQIDLOXUHLVH[SHFWHG
5HYLVHGWH[W
$SSUR[LPDWHO\  VXEMHFWV ZLOO EH VFUHHQHG DV  VXEMHFWV DUH SODQQHG WR EH
UDQGRPLVHGDQG D RIVFUHHQIDLOXUH UDWH LVH[SHFWHG

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
108
6HFWLRQ± 3UHSDUDWLRQ+DQGOLQJ6WRUDJH$FFRXQWDELOLW\
2ULJLQDOWH[W
$OO))9, DQGFRPSDUDWLYH,&6/$%$PDLQWHQDQFHWKHUDS\SUHVFULEHGWKURXJKRXWWKH
VWXG\ZLOOEHGLVSHQVHGDWDQGFROOHFWHG IURPWKHLQYHVWLJDWRUVLWH
,QYHVWLJDWLRQDOSURGXFWPXVWEHVWRUHGLQDVHFXUHDUHDXQGHUWKHDSSURSULDWHSK\VLFDO
FRQGLWLRQVIRUWKHSURGXFW$OO'3,VFRQWDLQLQJ))9,PXVWEHVWRUHGDWDWHPSHUDWXUHRI
XSWR&%XGHVRQLGH)RUPRWHURODQG)OXWLFDVRQH3URSLRQDWH6DOPHWHURO'3,VPXVWEH
VWRUHGDWDWHPSHUDWXUHRIXSWR&
5HYLVHGWH[W
$OO))9, DQGFRPSDUDWLYH,&6/$%$PDLQWHQDQFHWKHUDS\SUHVFULEHGWKURXJKRXWWKH
VWXG\ZLOOEHGLVSHQVHGDWDQGFROOHFWHGIURPWKHLQYHVWLJDWRUVLWH
,QYHVWLJDWLRQDOSURGXFWPXVWEHVWRUHGLQDVHFXUHDUHDXQGHUWKHDSSURSULDWHSK\VLFDO
FRQGLWLRQVIRUWKHSURGXFW$OO'3,VFRQWDLQLQJ))9,PXVWEHVWRUHGDWDWHPSHUDWXUHRI
XSWR&%XGHVRQLGH)RUPRWHURO'3,VPXVWEHVWRUHGDWDWHPSHUDWXUHRIXSWR&
DQG)OXWLFDVRQH3URSLRQDWH6DOPHWHURO'3,VVWRUHGDW#&
6HFWLRQ± ,QYHVWLJDWLRQDO3URGXFW0DOIXQFWLRQ
1HZ7H[W
$Q\LQYHVWLJDWLRQDOSURGXFWLQKDOHUWKDWIDLOVWRIXQFWLRQSURSHUO\PXVWEHLGHQWLILHG
WR*6.SHUVRQQHO'HWDLOVRIWKHIDLOXUH ZLOOEHGRFXPHQWHGLQWKHH&5) (OOLSWD
LQKDOHUVZLOOEHUHWXUQHGWR*6.IRUWHVWLQJ7KHVXEMHFWVKRXOGUHWXUQWKHLQKDOHU
WRWKHFOLQLFDVVRRQDVSRVVLEOHWRDYRLGPLVVLQJDQ\GRVHV7KHVLWHZLOOWKHQFRQWDFW
*6.¶VLQWHUQDO,:56DOVRNQRZQDVWKH5HJLVWUDWLRQDQG0HGLFDWLRQ2UGHULQJ
6\VWHP>5$026@1* DQGREWDLQDQHZWUHDWPHQWSDFNQXPEHUIRUWKLVVXEMHFW
DQGGLVSHQVHDQHZVWXG\PHGLFDWLRQNLWIURPWKHVLWH
VLQYHVWLJDWLRQDOSURGXFW
VXSSO\DVLQVWUXFWHGSHUWKH,:56
6HFWLRQ± 7LPHDQG(YHQWV7DEOH
2ULJLQDOWDEOH
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone 
call 1
Visit 
4**
Visit 5
Phone 
call 2
Visit 6
Early 
Withdrawal
Study week (± specified 
no. of days)
'D\WR

'D\
:HHN
 
GD\V
:HHN


GD\V
:HHN
 
GD\V
:HHN


GD\V
Early 
Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
Assessments

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
109
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone 
call 1
Visit 
4**
Visit 5
Phone 
call 2
Visit 6
Early 
Withdrawal
Study week (± specified 
no. of days)
'D\WR

'D\
:HHN
 
GD\V
:HHN


GD\V
:HHN
 
GD\V
:HHN


GD\V
Early 
Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
,QIRUPHG&RQVHQW
x
(OLJLELOLW\FULWHULD
x
x
'HPRJUDSK\
x
6PRNLQJVWDWXV
x
0HGLFDO)DPLO\ KLVWRU\ RI
FRQVHQWHGVXEMHFWVLQFOXGLQJ
&9
5LVN
IDFWRUV
DQG
H[DFHUEDWLRQKLVWRU\
x
3*[VDOLYDVDPSOH
x
3K\VLFDOH[DPLQDWLRQ
x
x
x
x
x
Safety Assessments
8ULQH3UHJQDQF\7HVW
x
x
x
x
([DFHUEDWLRQ$VVHVVPHQW
x
x
x
x
x
x
9LWDOVLJQV
x
x
x
x
x
6HULRXV $GYHUVH (YHQW DQG
$GYHUVH
'UXJ
5HDFWLRQ
$VVHVVPHQW
x
x
x
x
x
x
Efficacy Assessments
6SLURPHWU\
7HVWLQJ
3UH
GRVHWURXJK)(9
x
x
x 
Subject Questionnaires 
$VWKPD&RQWURO7HVW
x
x
x
x
x
x
x
(4'
x
x
x
$VWKPD4XDOLW\RI
/LIH4XHVWLRQQDLUH
x
x
x
0$56$TXHVWLRQQDLUH
x
x
x
x
3DWLHQW
6DWLVIDFWLRQ
DQG
3UHIHUHQFH3$6$34
x
x
Inhaler 
correct 
use 
assessment
7\SH$RYHUDOO HUURUVUHFRUG
x
x
x
Medication Assessments
&RQFRPLWDQW
0HGLFDWLRQ
$VVHVVPHQW
x
x
x
x
x
'LVSHQVH6WXG\0HGLFDWLRQð
x
x
&ROOHFW6WXG\0HGLFDWLRQð
x
x
x
RAMOS/eCRF
5$0261*
x
x
H&5)
x
x
x
x
x
x
x

6$(DQG$'5PRQLWRULQJZLOORFFXUIURP'D\6$(UHODWHGWRVWXG\SDUWLFLSDWLRQVKRXOGEHJLQIURPVLJQLQJRI
,&)$QDGGLWLRQDOVDIHW\DQG$&7FKHFNLVSURYLGHGE\SKRQHDWZHHNDQG

7KURXJKRXWWKHVWXG\WKHVWXG\PHGLFDWLRQZLOOEHGLVSHQVHGDQGFROOHFWHGE\WKHLQYHVWLJDWRUVLWH
9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLVXVXDODVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH
7KHQWKLVYLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEHFROOHFWHGDWWKLVYLVLW:ULWWHQ,QIRUPHG&RQVHQWPXVW
EHREWDLQHGSULRUWRLQLWLDWLRQRIVWXG\SURFHGXUHVRULQLWLDWLQJFKDQJHVLQPHGLFDWLRQV
 9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW 5DQGRPLVDWLRQYLVLW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
110
3*[VDOLYDVDPSOHFROOHFWHGDW9LVLW5DQGRPLVDWLRQRUDQ\VFKHGXOHGFOLQLFYLVLWWKHUHDIWHU
2QO\LIHDUO\ZLWKGUDZDORFFXUVEHIRUH:HHN
 2QO\IRUFKLOGEHDULQJZRPHQ
5HYLVHGWDEOH
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone 
call 1
Visit 
4**
Visit 5
Phone 
call 2
Visit 6
Early 
Withdrawal
Study week (± specified 
no. of days)
'D\WR

'D\
:HHN
 
GD\V
:HHN


GD\V
:HHN
 
GD\V
:HHN


GD\V
Early 
Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
Assessments
,QIRUPHG&RQVHQW
x
(OLJLELOLW\FULWHULD
x
x
'HPRJUDSK\
x
6PRNLQJVWDWXV
x
0HGLFDO)DPLO\ KLVWRU\ RI
FRQVHQWHGVXEMHFWVLQFOXGLQJ
&9
5LVN
IDFWRUV
DQG
H[DFHUEDWLRQKLVWRU\
x
3*[VDOLYDVDPSOH
x
3K\VLFDOH[DPLQDWLRQ
x
x
x
x
x
Safety Assessments
8ULQH3UHJQDQF\7HVW
x
x
x
x
([DFHUEDWLRQ$VVHVVPHQW
x
x
x
x
x
x
9LWDOVLJQV
x
x
x
x
x
6HULRXV $GYHUVH (YHQW DQG
$GYHUVH
'UXJ
5HDFWLRQ
$VVHVVPHQW
x
x
x
x
x
x
Efficacy Assessments
6SLURPHWU\
7HVWLQJ
3UH
GRVHWURXJK)(9
x
x
x 
Subject Questionnaires 
$VWKPD&RQWURO7HVW
x
x
x
x
x
x
x
(4'
x
x
x
$VWKPD4XDOLW\RI
/LIH4XHVWLRQQDLUH
x
x
x
0$56$TXHVWLRQQDLUH
x
x
x
x
3DWLHQW
6DWLVIDFWLRQ
DQG
3UHIHUHQFH3$6$34
x
x
Inhaler 
correct 
use 
assessment
Critical and non-critical 
errors record
x
x
x
Medication Assessments
&RQFRPLWDQW
0HGLFDWLRQ
$VVHVVPHQW
x
x
x
x
x
'LVSHQVH6WXG\0HGLFDWLRQð
x
x
&ROOHFW6WXG\0HGLFDWLRQð
x
x
x

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
111
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone 
call 1
Visit 
4**
Visit 5
Phone 
call 2
Visit 6
Early 
Withdrawal
Study week (± specified 
no. of days)
'D\WR

'D\
:HHN
 
GD\V
:HHN


GD\V
:HHN
 
GD\V
:HHN


GD\V
Early 
Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
RAMOS/eCRF
5$0261*
x
x
H&5)
x
x
x
x
x
x
x

6$(DQG$'5PRQLWRULQJZLOORFFXUIURP'D\6$(UHODWHGWRVWXG\SDUWLFLSDWLRQVKRXOGEHJLQIURPVLJQLQJRI
,&)$QDGGLWLRQDOVDIHW\DQG$&7FKHFNLVSURYLGHGE\SKRQHDWZHHNDQG

7KURXJKRXWWKHVWXG\WKHVWXG\PHGLFDWLRQZLOOEHGLVSHQVHGDQGFROOHFWHGE\WKHLQYHVWLJDWRUVLWH
9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLVXVXDODVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH
7KHQWKLVYLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEHFROOHFWHGDWWKLVYLVLW:ULWWHQ,QIRUPHG&RQVHQWPXVW
EHREWDLQHGSULRUWRLQLWLDWLRQRIVWXG\SURFHGXUHVRULQLWLDWLQJFKDQJHVLQPHGLFDWLRQV
 9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW 5DQGRPLVDWLRQYLVLW
3*[VDOLYDVDPSOHFROOHFWHGDW9LVLW5DQGRPLVDWLRQRUDQ\VFKHGXOHGFOLQLFYLVLWWKHUHDIWHU
2QO\LIHDUO\ZLWKGUDZDORFFXUVEHIRUH:HHN
2QO\IRUFKLOGEHDULQJZRPHQ
Note: All adverse events will be recorded in the source documents but only information regarding non-serious 
adverse drug reactions (ADRs) and serious adverse events (SAEs) will be documented and reported in the 
eCRF.
6HFWLRQ,QKDOHU&RUUHFW8VH$VVHVVPHQW
2ULJLQDOWH[W
&RUUHFWXVHRIWKHLQKDOHUZLOOEHDVVHVVHGDVRXWOLQHGLQWKH7LPHDQG(YHQWV7DEOH
6HFWLRQ
7DEOH
/LVWRI7\SH$OLNHO\WREHFULWLFDODQGRYHUDOOHUURUV IRU(OOLSWD70
7\SH$HUURUV IRU(OOLSWD70
\HV
QR
2YHUDOOHUURUV IRU(OOLSWD70
\HV
QR
)DLOHGWRRSHQFRYHU
1R
H[KDODWLRQ
EHIRUH
DQ
LQKDOLQJ
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
%ORFNHG
DLU
LQOHW
GXULQJ
LQKDODWLRQPDQRHXYUH
6KRRNWKHGHYLFHXSVLGHGRZQDIWHU
GRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUH

ORQJ

VWHDG\

GHHS
,QKDODWLRQ IURP PRXWKSLHFH NHSW
EHWZHHQOLSV
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
'LGQRWKROGEUHDWK

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
112
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHH
WH[WER[@
7DEOH
/LVW7\SH$OLNHO\WREHFULWLFDODQGRYHUDOOHUURUV IRU'LVNXV70
7\SH$HUURUVIRU'LVNXV70
\HV
QR
2YHUDOOHUURUVIRU'LVNXV70
\HV
QR
)DLOHGWRRSHQFRYHU
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
/HYHULVQRWSXVKHGEDFN
,QKDODWLRQPDQRHXYUH

VWHDG\

GHHS
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWKROGEUHDWK
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHH
WH[WER[@
7DEOH
/LVWRI7\SH$OLNHO\WREHFULWLFDOHUURUVDQGRYHUDOOHUURUV IRU
7XUEXKDOHU
7\SH$HUURUVIRU7XUEXKDOHU
\HV
QR
2YHUDOOHUURUVIRU
7XUEXKDOHU
\HV
QR
)DLOHGWRUHPRYHFDS
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
'LGQRWKROGGHYLFHXSULJKW
2.GXULQJGRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUH

IRUFHIXO

GHHS
1RWHWR+&3 LWLVLPSRUWDQW
WKDWWKHLQKDODWLRQLVIRUFHIXO
DQGGHHSIURPWKHVWDUWIRU
WKLVLQKDOHU
%DVHQRWWZLVWHGIXOO\EDFNZDUGV
DQGIRUZDUGVQRFOLFNKHDUG
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
'LGQRWKROGEUHDWK

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
113
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
$Q\RWKHUFRPPHQWV>IUHH
WH[WER[@
5HYLVHGWH[W
&RUUHFWXVHRIWKHLQKDOHUZLOOEHDVVHVVHGDVRXWOLQHGLQWKH7LPHDQG(YHQWV7DEOH
6HFWLRQ
7DEOH
&ULWLFDODQG1RQFULWLFDOHUURUVIRU(OOLSWD70
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURULV
GHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDO
PHGLFDWLRQEHLQJLQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@1R
>@<HVLI\HVWLFNDSSURSULDWHRSWLRQVEHORZ
&ULWLFDO(UURUV IRU(OOLSWD70
\HV
QR
1RQFULWLFDO
(UURUV
IRU
(OOLSWD70
\HV
QR
)DLOHGWRRSHQFRYHU
1R
H[KDODWLRQ
EHIRUH
DQ
LQKDODWLRQ
6KRRN WKH GHYLFH XSVLGH GRZQ
DIWHUGRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUH ZDV
QRW

ORQJ

VWHDG\

GHHS
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH

1RVHDOE\WKHOLSVDURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWKROGEUHDWK
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
114
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUVIRU'LVNXV70
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURULV
GHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDO
PHGLFDWLRQEHLQJLQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@1R
>@<HVLI\HVWLFNDSSURSULDWHRSWLRQVEHORZ
&ULWLFDO(UURUV IRU'LVNXV70
\HV
QR
1RQFULWLFDO(UURUV IRU
'LVNXV70
\HV
QR
)DLOHGWRRSHQFRYHU
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
/HYHULVQRWSXVKHGEDFN
,QKDODWLRQPDQRHXYUH ZDV
QRW

VWHDG\

GHHS
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
'LGQRWKROGEUHDWK
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@
7DEOH
&ULWLFDODQG1RQFULWLFDO HUURUV IRU7XUEXKDOHU
,QVWUXFWLRQV&ULWLFDO(UURUVDUHLGHQWLILHGLQEROGWH[WLQWKHOLVWEHORZ$FULWLFDOHUURU
LVGHILQHGDVDQHUURUWKDWLVPRVWOLNHO\WRUHVXOWLQQRRURQO\PLQLPDO
PHGLFDWLRQEHLQJLQKDOHG&KHFNRQO\RQHER[
'LGWKHVXEMHFWPDNHDQHUURUZKLOHXVLQJWKHGHYLFH"
>@ 1R
>@<HV LI\HVWLFNDSSURSULDWH RSWLRQVEHORZ
&ULWLFDO(UURUV IRU7XUEXKDOHU
\HV
QR
1RQFULWLFDO(UURUV IRU
7XUEXKDOHU
\HV
QR
)DLOHGWRUHPRYHFDS
'HYLFHWLSSHGGRZQZDUGV
DIWHUGRVHSUHSDUDWLRQ
'LGQRWKROGGHYLFHXSULJKW
2.GXULQJGRVHSUHSDUDWLRQ
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
115
%DVHQRWWZLVWHGIXOO\EDFNZDUGV
DQGIRUZDUGVQRFOLFNKHDUG
,QKDODWLRQPDQRHXYUH ZDV
QRW

IRUFHIXO

GHHS
1RWHWR+&3 LWLVLPSRUWDQW
WKDWWKHLQKDODWLRQLVIRUFHIXO
DQGGHHSIURPWKHVWDUWIRU
WKLVLQKDOHU
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWKROGEUHDWK
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHHWH[WER[@
6HFWLRQ7URXJKSUHGRVH)(9DVVHVVPHQW
2ULJLQDOWH[W
$OO VLWHV ZLOO XVH VWDQGDUGLVHG VSLURPHWU\ HTXLSPHQW SURYLGHG E\ *6. )RU HDFK
REVHUYDWLRQ DW OHDVW  YDOLG ZLWK QR PRUH WKDQ  HIIRUWV ZLOO EH REWDLQHG 7KH EHVW
)(9YDOXHZLOOEHUHFRUGHGLQWKHH&5)
5HYLVHGWH[W
$OO VLWHV ZLOO XVH VWDQGDUGLVHG VSLURPHWU\ HTXLSPHQW SURYLGHG E\ *6. )RU HDFK
REVHUYDWLRQDWOHDVWZLWKQRPRUHWKDQHIIRUWVZLOOEHREWDLQHG$WOHDVWWZRRIWKH
VSLURPHWU\HIIRUWVVKRXOGEHDFFHSWDEOHDQGUHSHDWDEOH 7KHEHVW)(9YDOXHZLOOEH
UHFRUGHGLQWKHH&5)
6HFWLRQ&OLQLFDO6DIHW\/DERUDWRU\$VVHVVPHQW
2ULJLQDOWH[W
$Q\ DEQRUPDO ODERUDWRU\ WHVW UHVXOWV KHPDWRORJ\ FOLQLFDO FKHPLVWU\ RU XULQDO\VLV RU
RWKHU VDIHW\ DVVHVVPHQWV HJ (&*V UDGLRORJLFDO VFDQV YLWDO VLJQV PHDVXUHPHQWV
LQFOXGLQJ WKRVH WKDW ZRUVHQ IURP EDVHOLQH DQG IHOW WR EH FOLQLFDOO\ VLJQLILFDQW LQ WKH
PHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKH ,QYHVWLJDWRUDUHWREHUHFRUGHGDVQRQVHULRXV
$'5VRU6$(VDVDSSURSULDWH

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
116
5HYLVHGWH[W
7KHUHDUHQRFOLQLFDOVDIHW\ODERUDWRU\DVVHVVPHQWUHTXLUHPHQWVIRUWKLVVWXG\
$Q\ DEQRUPDO ODERUDWRU\ WHVW UHVXOWV KHPDWRORJ\ FOLQLFDO FKHPLVWU\ RU XULQDO\VLV RU
RWKHU VDIHW\ DVVHVVPHQWV HJ (&*V UDGLRORJLFDO VFDQV YLWDO VLJQV PHDVXUHPHQWV
UHFRUGHGGXULQJDURXWLQHFOLQLFYLVLWLQFOXGLQJWKRVHWKDWZRUVHQIURPEDVHOLQHDQG
IHOWWREHFOLQLFDOO\VLJQLILFDQWLQWKHPHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKH,QYHVWLJDWRU
DUHWREHUHFRUGHGDVQRQVHULRXV$'5VRU6$(VDVDSSURSULDWH
6HFWLRQ± $QDO\VLV3RSXODWLRQ
2ULJLQDOWH[W
3RSXODWLRQVFRQVLGHUHGIRUDQDO\VLVDUHDVIROORZV
,QWHQWWRWUHDW,77VHW$OOUDQGRPL]HGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQHGRVH
RIWKHSUHVFULSWLRQRIVWXG\PHGLFDWLRQ HLWKHU))9,RUXVXDO,&6/$%$DVWKPD
PDLQWHQDQFH WKHUDS\ 7KH ,77 VHW ZLOO EH XVHG WR DQDO\]H WKH SULPDU\ HIILFDF\
HQGSRLQW DQDO\VLV WKH VHFRQGDU\ HIILFDF\ HQGSRLQW DQG RWKHU HIILFDF\ HQGSRLQWV
6XEMHFWVZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVUDQGRPL]HGIRUWKH,77VHW
3HUSURWRFRO 33 VHW DOO ,77 VXEMHFWV ZLWKRXW DQ\ PDMRU YLRODWLRQV RI VWXG\
SURFHGXUHV 0DMRU SURWRFRO YLRODWLRQV ZLOO EH LGHQWLILHG SULRU WR GDWDEDVH ORFN
3URWRFROGHYLDWLRQVZLOOEHUHYLHZHGDQGFODVVLILHGDVPLQRURUPDMRUGXULQJDGDWD
UHYLHZPHHWLQJWKDWZLOOEHKHOGEHIRUHGDWDEDVHORFN7KHH[FOXVLRQRIVXEMHFWV
IURPWKH33VHWZLOOEHVSHFLILHGDQGGRFXPHQWHGLQWKH5$3
6DIHW\ VHW $OO HQUROOHG VXEMHFWV KDYLQJ UHFHLYHG DW OHDVW RQH GRVH RI WKH
SUHVFULSWLRQ RI VWXG\ PHGLFDWLRQ HLWKHU ))9, RU XVXDO ,&6/$%$ DVWKPD
PDLQWHQDQFHWKHUDS\DQGFRQVLGHUHGDVWUHDWHG7KH6DIHW\VHWZLOOEHWKHEDVLVIRU
VDIHW\DQDO\VHV6XEMHFWVZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVWUHDWHGIRUWKH
6DIHW\VHW
5HYLVHGWH[W
3RSXODWLRQVFRQVLGHUHGIRUDQDO\VLVDUHDVIROORZV
,QWHQWWRWUHDW,77SRSXODWLRQ$OOUDQGRPL]HGVXEMHFWVKDYLQJUHFHLYHGDWOHDVW
RQHGRVHRIWKHSUHVFULSWLRQRIVWXG\PHGLFDWLRQ HLWKHU))9,RUXVXDO,&6/$%$
DVWKPD PDLQWHQDQFH WKHUDS\ 7KH ,77 SRSXODWLRQ ZLOO EH XVHG WR DQDO\]H WKH
SULPDU\ HIILFDF\ HQGSRLQW DQDO\VLV WKH VHFRQGDU\ HIILFDF\ HQGSRLQW DQG RWKHU
HIILFDF\HQGSRLQWV6XEMHFWVZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVUDQGRPL]HG
IRUWKH,77SRSXODWLRQ
3HUSURWRFRO 33 SRSXODWLRQ DOO ,77 VXEMHFWV ZLWKRXW DQ\ PDMRU YLRODWLRQV RI
VWXG\SURFHGXUHV0DMRUSURWRFROYLRODWLRQVZLOOEHLGHQWLILHGSULRUWRGDWDEDVHORFN
3URWRFROGHYLDWLRQVZLOOEHUHYLHZHGDQGFODVVLILHGDVPLQRURUPDMRUGXULQJDGDWD

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
117
UHYLHZPHHWLQJWKDWZLOOEHKHOGEHIRUHGDWDEDVHORFN7KHH[FOXVLRQRIVXEMHFWV
IURPWKH33SRSXODWLRQ ZLOOEHVSHFLILHGDQGGRFXPHQWHGLQWKH5$3
6DIHW\SRSXODWLRQ $OOHQUROOHGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQHGRVHRIWKH
SUHVFULSWLRQ RI VWXG\ PHGLFDWLRQ HLWKHU ))9, RU XVXDO ,&6/$%$ DVWKPD
PDLQWHQDQFHWKHUDS\DQGFRQVLGHUHGDVWUHDWHG7KH6DIHW\SRSXODWLRQ ZLOOEHWKH
EDVLVIRUVDIHW\DQDO\VHV6XEMHFWVZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVWUHDWHG
IRUWKH6DIHW\SRSXODWLRQ
6HFWLRQ± .H\(OHPHQWVRI$QDO\VLV3ODQ
2ULJLQDOWH[W
7KHSULPDU\FRPSDULVRQRILQWHUHVWLVWKHFRPSDULVRQRIWKHFKDQJHIURPEDVHOLQH9LVLW
LQWKHWRWDO$&7VFRUHDVVHVVHGDW:HHN9LVLWEHWZHHQ))9,PFJPFJRU
PFJPFJ DQG XVXDO ,&6/$%$ LQKDODWLRQ SRZGHU IRU DVWKPD PDLQWHQDQFH
WKHUDS\
7KHSULPDU\VHWIRUDQDO\VLVLVWKHLQWHQWWRWUHDWVHW$VHQVLWLYLW\DQDO\VLVZLOOEH
SHUIRUPHGLQWKH33VHW
5HYLVHGWH[W
7KHSULPDU\FRPSDULVRQRILQWHUHVWLVWKHFRPSDULVRQRIWKHFKDQJHIURPEDVHOLQH9LVLW
LQWKHWRWDO$&7VFRUHDVVHVVHGDW:HHN9LVLWEHWZHHQ))9,PFJPFJRU
PFJPFJ DQG XVXDO ,&6/$%$ LQKDODWLRQ SRZGHU IRU DVWKPD PDLQWHQDQFH
WKHUDS\
7KHSULPDU\VHWIRUDQDO\VLVZLOOEHSHUIRUPHGRQ WKHLQWHQWWRWUHDWSRSXODWLRQ$
VHQVLWLYLW\DQDO\VLVZLOOEHSHUIRUPHGLQWKH33SRSXODWLRQ
6HFWLRQ± 3ULPDU\$QDO\VLV
2ULJLQDOWH[W
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7WRWDO
VFRUHDVVHVVHGDW:HHN9LVLW
7KHSULPDU\VHWRIDQDO\VLVLVWKH,77VHW
 1RQLQIHULRULW\WHVWLQJ
7KH QRQLQIHULRULW\ RI ))9, YHUVXV DQ\ RWKHU ,&6/$%$ '3, FRPSDUDWRU ZLOO EH
SULPDULO\WHVWHGLQDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFK7KHPRGHOZLOO
LQFOXGHIDFWRUVDQGFRYDULDWHVDVIROORZWUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN
DQG :HHN  EDVHOLQH $&7 WUHDWPHQW E\ YLVLW LQWHUDFWLRQ EDVHOLQH $&7 E\ YLVLW
LQWHUDFWLRQ JHQGHU DJH DQG SDWLHQW ZLOO EH ILWWHG DV D UDQGRP IDFWRU 7KH 5HVWULFWHG
0D[LPXP /LNHOLKRRG 5(0/ HVWLPDWLRQ DSSURDFK ZLOO EH XVHG DQG WKH GHIDXOW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
118
FRYDULDQFH VWUXFWXUH ZLOO EH XQVWUXFWXUHG  &RQVLVWHQW ZLWK 0050 PRGHO ILWWLQJ QR
H[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUDJLYHQWLPHSRLQWZLOOEHSHUIRUPHG7KH
FRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRUZLOO
EHHVWLPDWHGDW:HHN9LVLWLQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHGLIWKH
QRQLQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQ
WKHGLIIHUHQFHEHWZHHQ))9,DQGDQ\RWKHUFRPSDUDWRUSRVLWLYHYDOXHVRIWKHGLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\DQDO\VHV
H +DQGOLQJPLVVLQJGDWD
:KLOHVXEMHFWVPLVVLQJ:HHN9LVLWGDWDEXWKDYLQJHDUOLHUGDWDZLOOEHLQFOXGHGLQ
WKH0050SULPDU\DQDO\VLVWKHLQWHUSUHWDELOLW\RIWKHUHVXOWVIURPWKHSULPDU\PRGHO
ZLOOGHSHQGRQWKHPLVVLQJGDWDVDWLVI\LQJWKH0LVVLQJDW5DQGRP0$57RVXSSRUW
WKHYDOLGLW\RIWKHFRQFOXVLRQVGUDZQIURPWKLVDQDO\VLVVHYHUDOVHQVLWLYLW\DQDO\VHVZLOO
EH SHUIRUPHG WR H[SORUH WKH GURSRXW SDWWHUQ DQG LWV SRVVLEOH LPSDFW RQ WUHDWPHQW
FRPSDULVRQV
 0LVVLQJ YDOXHV DW :HHN  9LVLW  ZLOO EH UHSODFHG E\ WKH SRVW
UDQGRPL]DWLRQODVWDYDLODEOHYDOXHHLWKHUWKHZHHNEDVHG$&7VFRUHRUWKH
$&7 VFRUH DW WUHDWPHQW ZLWKGUDZDO WLPH LI DQ\ LH EDVHG RQ WKH /DVW
2EVHUYDWLRQ&DUULHG)RUZDUGPHWKRG7KHFKDQJHIURPEDVHOLQHLQ$&7DW
:HHN  9LVLW  ZLOO EH DQDO\]HG LQ DQ $1&29$ PRGHO DGMXVWLQJ IRU
WUHDWPHQW DQG EDVHOLQH $&7 VFRUH 7KH WUHDWPHQW HIIHFW ))9, YHUVXV DQ\
RWKHU,&6/$%$FRPSDUDWRUDQGLWVFRUUHVSRQGLQJFRQILGHQFHLQWHUYDO
ZLOOEHHVWLPDWHGLQWKLVPRGHOWRWHVWWKHQRQLQIHULRULW\K\SRWKHVLV
 0XOWLSOHLPSXWDWLRQ0,DQDO\VHVXWLOL]LQJFRYDULDWHVNQRZQWREHSUHGLFWLYH
RIUHVSRQVHVHDVRQDWUDQGRPL]DWLRQREVHUYHGYDOXHRI$&7DW:HHN
REVHUYHGYDOXHRI$&7DW:HHN9LVLW2WKHUFRYDULDWHVPD\EH
FRQVLGHUHGDQGLIVRLWZLOOEHGHWDLOHGLQWKH5$3
6WHS   )RU HDFK WUHDWPHQW JURXS VHSDUDWHO\ PLVVLQJ PHDVXUHPHQWV DUH
LPSXWHG IRU VXEMHFWV ZLWK D EDVHOLQH PHDVXUHPHQW ZKHUH WKHUH DUH PLVVLQJ
REVHUYDWLRQVDWHLWKHU:HHNRU:HHNXVLQJWKHDERYHFRYDULDWHVDQG
UHJUHVVLRQEDVHG LPSXWDWLRQ PHWKRG 7KH 0DUNRY &KDLQ 0RQWH &DUOR
0&0&PHWKRGIRU0,ZLOOEH XVHGDQGWHQVXFKVHWVRILPSXWHGGDWDZLOO
EHFUHDWHGHDFKZLWKWKHREVHUYHGYDOXHVRULPSXWHGYDOXHVIRUVXEMHFWVZLWK
PLVVLQJREVHUYDWLRQV
6WHS  (DFK LPSXWHG GDWD VHW ZLOO EH DQDO\]HG XVLQJ WKH SULPDU\ 0050
PRGHO7KHWUHDWPHQWHIIHFWIURPWKHVHDQDO\VHVZLOOWKHQEHSRROHGXVLQJ
VWDQGDUG0,WKHRU\WRPDNHDQRYHUDOOLQIHUHQFH7KHGLIIHUHQFHLQWKHOHDVW
VTXDUHV PHDQV EHWZHHQ WKH WZR JURXSV DW :HHN  9LVLW  DQG WKH
FRUUHVSRQGLQJFRQILGHQFHLQWHUYDOIRUWKHGLIIHUHQFHZLOOEHSUHVHQWHG
I
$ VHQVLWLYLW\ DQDO\VLV EDVHG RQ WKH VHPL SDUDPHWULF +RGJHV/HKPDQQ +/
DSSURDFKZLOOEHSURSRVHGWRDVVHVVWKHUREXVWQHVVRIWKH00500RGHOEDVHG

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
119
QRQLQIHULRULW\UHVXOWV7KH+/GLIIHUHQFHEHWZHHQJURXSVZLWKWKHFRUUHVSRQGLQJ
FRQILGHQFHLQWHUYDOZLOOEHSURYLGHG
J 6HQVLWLYLW\ DQDO\VHV IRU KDQGOLQJ WUHDWPHQW ZLWKGUDZDO ZKHQ WUHDWPHQW
ZLWKGUDZDORFFXUVDQDOWHUQDWLYHPHWKRGIRULPSXWLQJWKHPLVVLQJYDOXHDWWKH
QHDUHVWYLVLWDIWHUZLWKGUDZDOWLPHZLOOEHSURSRVHGWKHSULPDU\HQGSRLQWPLVVLQJ
YDOXHZLOOEHHVWLPDWHGE\WKHZRUVW$&7VFRUHREVHUYHGEHWZHHQEDVHOLQHYLVLW
LQFOXGHGDQGZLWKGUDZDOWLPHLQFOXGHG
K 7KH SULPDU\ DQDO\VLV LH EDVHG RQ WKH 0050 DSSURDFK DQG WKH VDPH
VHQVLWLYLW\DQDO\VHVSUHVHQWHGKHUHDERYHZLOOEHSHUIRUPHGLQ WKH3HU3URWRFRO
VHW
5HYLVHGWH[W
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7WRWDO
VFRUHDVVHVVHGDW:HHN9LVLW
7KHSULPDU\SRSXODWLRQ RIDQDO\VLVZLOOEH WKH,77SRSXODWLRQ
 1RQLQIHULRULW\WHVWLQJ
7KH QRQLQIHULRULW\ RI ))9, YHUVXV DQ\ RWKHU ,&6/$%$ '3, FRPSDUDWRU ZLOO EH
SULPDULO\WHVWHGLQDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFK7KHPRGHOZLOO
LQFOXGHIDFWRUVDQGFRYDULDWHVDVIROORZWUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN
DQG :HHN  EDVHOLQH $&7 WUHDWPHQW E\ YLVLW LQWHUDFWLRQ EDVHOLQH $&7 E\ YLVLW
LQWHUDFWLRQ JHQGHU DJH DQG SDWLHQW ZLOO EH ILWWHG DV D UDQGRP IDFWRU 7KH 5HVWULFWHG
0D[LPXP /LNHOLKRRG 5(0/ HVWLPDWLRQ DSSURDFK ZLOO EH XVHG DQG WKH GHIDXOW
FRYDULDQFH VWUXFWXUH ZLOO EH XQVWUXFWXUHG  &RQVLVWHQW ZLWK 0050 PRGHO ILWWLQJ QR
H[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUDJLYHQWLPHSRLQWZLOOEHSHUIRUPHG7KH
FRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRUZLOO
EHHVWLPDWHGDW:HHN9LVLWLQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHGLIWKH
QRQLQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQ
WKHGLIIHUHQFHEHWZHHQ))9,DQGDQ\RWKHUFRPSDUDWRUSRVLWLYHYDOXHVRIWKHGLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\DQDO\VHV
L
+DQGOLQJPLVVLQJGDWD
:KLOHVXEMHFWVPLVVLQJ:HHN9LVLWGDWDEXWKDYLQJHDUOLHUGDWDZLOOEHLQFOXGHGLQ
WKH0050SULPDU\DQDO\VLVWKHLQWHUSUHWDELOLW\RIWKHUHVXOWVIURPWKHSULPDU\PRGHO
ZLOOGHSHQGRQWKHPLVVLQJGDWDVDWLVI\LQJWKH0LVVLQJDW5DQGRP0$57RVXSSRUW
WKHYDOLGLW\RIWKHFRQFOXVLRQVGUDZQIURPWKLVDQDO\VLVVHYHUDOVHQVLWLYLW\DQDO\VHVZLOO
EH SHUIRUPHG WR H[SORUH WKH GURSRXW SDWWHUQ DQG LWV SRVVLEOH LPSDFW RQ WUHDWPHQW
FRPSDULVRQV
 0LVVLQJ YDOXHV DW :HHN  9LVLW  ZLOO EH UHSODFHG E\ WKH SRVW
UDQGRPL]DWLRQODVWDYDLODEOHYDOXHHLWKHUWKHZHHNEDVHG$&7VFRUHRUWKH
$&7 VFRUH DW WUHDWPHQW ZLWKGUDZDO WLPH LI DQ\ LH EDVHG RQ WKH /DVW

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
120
2EVHUYDWLRQ&DUULHG)RUZDUGPHWKRG7KHFKDQJHIURPEDVHOLQHLQ$&7DW
:HHN  9LVLW  ZLOO EH DQDO\]HG LQ DQ $1&29$ PRGHO DGMXVWLQJ IRU
WUHDWPHQW DQG EDVHOLQH $&7 VFRUH 7KH WUHDWPHQW HIIHFW ))9, YHUVXV DQ\
RWKHU,&6/$%$FRPSDUDWRUDQGLWVFRUUHVSRQGLQJFRQILGHQFHLQWHUYDO
ZLOOEHHVWLPDWHGLQWKLVPRGHOWRWHVWWKHQRQLQIHULRULW\K\SRWKHVLV
 0XOWLSOHLPSXWDWLRQ0,DQDO\VHVXWLOL]LQJFRYDULDWHVNQRZQWREHSUHGLFWLYH
RIUHVSRQVHVHDVRQDWUDQGRPL]DWLRQREVHUYHGYDOXHRI$&7DW:HHN
REVHUYHGYDOXHRI$&7DW:HHN9LVLW2WKHUFRYDULDWHVPD\EH
FRQVLGHUHGDQGLIVRLWZLOOEHGHWDLOHGLQWKH5$3
6WHS   )RU HDFK WUHDWPHQW JURXS VHSDUDWHO\ PLVVLQJ PHDVXUHPHQWV DUH
LPSXWHG IRU VXEMHFWV ZLWK D EDVHOLQH PHDVXUHPHQW ZKHUH WKHUH DUH PLVVLQJ
REVHUYDWLRQVDWHLWKHU:HHNRU:HHNXVLQJWKHDERYH FRYDULDWHVDQG
UHJUHVVLRQEDVHG LPSXWDWLRQ PHWKRG 7KH 0DUNRY &KDLQ 0RQWH &DUOR
0&0&PHWKRGIRU0,ZLOOEHXVHGDQGWHQVXFKVHWVRILPSXWHGGDWDZLOO
EHFUHDWHGHDFKZLWKWKHREVHUYHGYDOXHVRULPSXWHGYDOXHVIRUVXEMHFWVZLWK
PLVVLQJREVHUYDWLRQV
6WHS  (DFK LPSXWHG GDWD VHW ZLOO EH DQDO\]HG XVLQJ WKH SULPDU\ 0050
PRGHO7KHWUHDWPHQWHIIHFWIURPWKHVHDQDO\VHVZLOOWKHQEHSRROHGXVLQJ
VWDQGDUG0,WKHRU\WRPDNHDQRYHUDOOLQIHUHQFH7KHGLIIHUHQFHLQWKHOHDVW
VTXDUHV PHDQV EHWZHHQ WKH WZR JURXSV DW :HHN  9LVLW  DQG WKH
FRUUHVSRQGLQJFRQILGHQFHLQWHUYDOIRUWKHGLIIHUHQFHZLOOEHSUHVHQWHG
M
$ VHQVLWLYLW\ DQDO\VLV EDVHG RQ WKH VHPL SDUDPHWULF +RGJHV/HKPDQQ +/
DSSURDFKZLOOEHSURSRVHGWRDVVHVVWKHUREXVWQHVVRIWKH00500RGHOEDVHG
QRQLQIHULRULW\UHVXOWV7KH+/GLIIHUHQFHEHWZHHQJURXSVZLWKWKHFRUUHVSRQGLQJ
FRQILGHQFHLQWHUYDOZLOOEHSURYLGHG
N 6HQVLWLYLW\ DQDO\VHV IRU KDQGOLQJ WUHDWPHQW ZLWKGUDZDO ZKHQ WUHDWPHQW
ZLWKGUDZDORFFXUVDQDOWHUQDWLYHPHWKRGIRULPSXWLQJWKHPLVVLQJYDOXHDWWKH
QHDUHVWYLVLWDIWHUZLWKGUDZDOWLPHZLOOEHSURSRVHGWKHSULPDU\HQGSRLQWPLVVLQJ
YDOXHZLOOEHHVWLPDWHGE\WKHZRUVW$&7VFRUHREVHUYHGEHWZHHQEDVHOLQHYLVLW
LQFOXGHGDQGZLWKGUDZDOWLPHLQFOXGHG
O
7KH SULPDU\ DQDO\VLV LH EDVHG RQ WKH 0050 DSSURDFK DQG WKH VDPH
VHQVLWLYLW\DQDO\VHVSUHVHQWHGKHUHDERYHZLOOEHSHUIRUPHGRQ WKH3HU3URWRFRO
SRSXODWLRQ
6HFWLRQ± 6HFRQGDU\$QDO\VHV2WKHU6HFRQGDU\$QDO\VHV
2ULJLQDOWH[W
3URSHUXVHRIWKHPHGLFDOGHYLFH
7KHRWKHUNH\VHFRQGDU\HQGSRLQWZLOOEHWKHFRUUHFWXVHRIWKHLQKDOHUGHYLFHDVVHVVHGDW
UDQGRPLVDWLRQ9LVLWDW:HHN9LVLWDQGDW:HHN9LVLW7KHGHYLFHZLOO
EHFRQVLGHUHGDVDGHTXDWHO\XVHGLIWKHSDWLHQWGLGQ¶WPDNHDQ\7\SH$HUURUDOOFULWLFDO
LWHPVFRUUHFWDWWKHFRUUHVSRQGLQJYLVLWVUDQGRPLVDWLRQ>9LVLW@ZHHN>9LVLW@DQG

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
121
ZHHN>9LVLW@3URSRUWLRQVRIVXEMHFWVFRUUHFWO\XVLQJWKHGHYLFHZLOOEHHVWLPDWHG
ZLWKLQ HDFK JURXS $ FRUUHVSRQGLQJ  FRQILGHQFH LQWHUYDO RI WKH GLIIHUHQFH LQ
SURSRUWLRQVZLOODOVREHSURYLGHG$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHG
DQGZLOOEHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGQRFDXVDODVVRFLDWLRQ
ZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV
5HYLVHGWH[W
3URSHUXVHRIWKHPHGLFDOGHYLFH
7KHRWKHUNH\VHFRQGDU\HQGSRLQWZLOOEHWKHFRUUHFWXVHRIWKHLQKDOHUGHYLFHDVVHVVHGDW
UDQGRPLVDWLRQ9LVLWDW:HHN9LVLWDQGDW:HHN9LVLW7KHGHYLFHZLOO
EH FRQVLGHUHG DV DGHTXDWHO\ XVHG LI WKH SDWLHQW GLGQ¶W PDNH DQ\ FULWLFDO HUURU DW WKH
FRUUHVSRQGLQJYLVLWVUDQGRPLVDWLRQ>9LVLW@ZHHN>9LVLW@DQGZHHN>9LVLW@
3URSRUWLRQVRIVXEMHFWVFRUUHFWO\XVLQJWKHGHYLFHZLOOEHHVWLPDWHGZLWKLQHDFKJURXS$
FRUUHVSRQGLQJ  FRQILGHQFH LQWHUYDO RI WKH GLIIHUHQFH LQ SURSRUWLRQV ZLOO DOVR EH
SURYLGHG$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOOEHGHWDLOHGLQWKH
5$3(YHQLIWHVWVZLOOEHSHUIRUPHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVH
DQDO\VHV
6HFWLRQ± 2WKHU$QDO\VHV&KDQJHIURPEDVHOLQHLQSUHGRVH
WURXJK)(9
2ULJLQDOWH[W
7KHDQDO\VLVRIWKHRWKHUHQGSRLQWVGHILQHGLQWKLVVHFWLRQZLOOEHSURYLGHGIRU
H[SORUDWRU\SXUSRVHVRQO\$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOO
EHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOO EHSHUIRUPHGDQGFRQILGHQFHLQWHUYDOVZLOO
EHSURYLGHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV
&KDQJHIURPEDVHOLQHLQSUHGRVHWURXJK)(9
5HVXOWVZLOOEHVXPPDUL]HGIRUHDFKJURXSDQGWKHUHVXOWVRIWKHGLIIHUHQFHEHWZHHQ
JURXSV ZLOOEHSUHVHQWHGZLWKWKHFRUUHVSRQGLQJFRQILGHQFHLQWHUYDODW:HHN
9LVLW
5HVSRQVHWRWUHDWPHQW
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW25DSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7FKDQJH
7KHUHVSRQGHUDQDO\VHVZLOOEHFRQGXFWHGXVLQJDORJLVWLFUHJUHVVLRQPRGHODWDJLYHQ
9LVLWRU3KRQH&DOODGMXVWLQJIRUWUHDWPHQWDQGVWUDWLILFDWLRQIDFWRUVEDVHOLQH$&7VFRUH
FDWHJRUL]HG LQWR WZR FODVVHV EDVHOLQH DVWKPD WKHUDS\ DQG SRWHQWLDOO\ VHDVRQ DW
UDQGRPL]DWLRQ 7UHDWPHQW E\ VWUDWLILFDWLRQ IDFWRUV LQWHUDFWLRQ HIIHFWV ZLOO EH IXUWKHU
LQYHVWLJDWHGLQDGGLWLRQDOORJLVWLFPRGHOVDGMXVWLQJIRUWKHVHVSHFLILFHIIHFWV

2017N339371_00

2014N190259_01
&21),'(17,$/
HZA116492
122
5HYLVHGWH[W
7KHDQDO\VLVRIWKHRWKHUHQGSRLQWVGHILQHGLQWKLVVHFWLRQZLOOEHSURYLGHGIRU
H[SORUDWRU\SXUSRVHVRQO\$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOO
EHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGDQGFRQILGHQFHLQWHUYDOVZLOO
EHSURYLGHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV
&KDQJHIURPEDVHOLQHLQSUHGRVHWURXJK)(9
5HVXOWVZLOOEHVXPPDUL]HGIRUHDFKJURXSDW:HHN9LVLW 0RUHGHWDLOZLOOEH
SURYLGHGLQWKH5$3
5HVSRQVHWRWUHDWPHQW
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW25DSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7FKDQJH
7KHUHVSRQGHUDQDO\VHVZLOOEHFRQGXFWHGXVLQJDORJLVWLFUHJUHVVLRQPRGHODWDJLYHQ
9LVLWRU3KRQH&DOODGMXVWLQJIRUWUHDWPHQWDQGVWUDWLILFDWLRQIDFWRUVEDVHOLQH$&7VFRUH
FDWHJRUL]HG LQWR WZR FODVVHV EDVHOLQH DVWKPD WKHUDS\ DQG SRWHQWLDOO\ VHDVRQ DW
UDQGRPL]DWLRQ 7UHDWPHQW E\ VWUDWLILFDWLRQ IDFWRUV LQWHUDFWLRQ HIIHFWV ZLOO EH IXUWKHU
LQYHVWLJDWHGLQDGGLWLRQDOORJLVWLFPRGHOVDGMXVWLQJIRUWKHVHVSHFLILFHIIHFWV
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW
7KHIUHTXHQF\DQGWKHSHUFHQWDJHRIVXEMHFWVZLWK$&7VFRUHDWDJLYHQYLVLW
ZLOOEHGHVFULEHGE\WUHDWPHQWJURXS0RUHGHWDLOZLOOEHSURYLGHGLQWKH5$3
!
&KDQJHIURPEDVHOLQHLQLQGLYLGXDOTXHVWLRQVFRUHVIRU$&7DWDJLYHQYLVLW
)RUHDFKTXHVWLRQWKHVWDWLVWLFDOSDUDPHWHUVRIWKHFKDQJHVZLOOEHVXPPDUL]HGE\
WUHDWPHQWJURXS0RUHGHWDLOZLOOEHSURYLGHGLQWKH5$3

2017N339371_00

2014N190259_00
&21),'(17,$/
7KH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV
HZA116492
1
7,7/(3$*(
'LYLVLRQ:RUOGZLGH'HYHORSPHQW
,QIRUPDWLRQ7\SH&OLQLFDO3URWRFRO
7LWOH
$PRQWKRSHQODEHOUDQGRPLVHGHIILFDF\VWXG\WRHYDOXDWH
IOXWLFDVRQHIXURDWH))*:YLODQWHURO9,
*:,QKDODWLRQ3RZGHUGHOLYHUHGRQFHGDLO\YLDWKH
'U\3RZGHU,QKDOHU(OOLSWDFRPSDUHGZLWKXVXDO,&6/$%$
PDLQWHQDQFHWKHUDS\GHOLYHUHGE\'U\3RZGHU,QKDOHULQ
VXEMHFWVZLWK3HUVLVWHQW$VWKPD
&RPSRXQG1XPEHU
*:*:
'HYHORSPHQW3KDVH
,,,E
(IIHFWLYH'DWH
)(%
6XEMHFW )OXWLFDVRQH)XURDWH9LODQWHURO'U\3RZGHU,QKDOHU(IILFDF\6DIHW\ 4XDOLW\
RI/LIH$VWKPD
$XWKRUV'U
0HGLFDO3URMHFW/HDGHU)UDQFH'U

5HVSLUDWRU\0HGLFDO'LUHFWRU)UDQFH
6WDWLVWLFDO&RRUGLQDWRU)UDQFH
2SHUDWLRQVDQG6FLHQFH/HDGHU)UDQFH
&OLQLFDO
'HYHORSPHQW'LUHFWRU0'&*OREDO&OLQLFDO'HYHORS8.5'5HVSLUDWRU\5	'

'LUHFWRU6(50*&636(50 'HYHORSPHQW8.5'&KLHI0HGLFDO2IILFH
&RS\ULJKW WKH*OD[R6PLWK.OLQHJURXSRIFRPSDQLHV$OOULJKWVUHVHUYHG
8QDXWKRULVHGFRS\LQJRUXVHRIWKLVLQIRUPDWLRQLVSURKLELWHG

2017N339371_00
33'
33'
33'
33'
33'
33'
33'


2017N339371_00
33'
33'

2014N190259_00
&21),'(17,$/
HZA116492
3
0(',&$/021,7256321625 ,1)250$7,213$*(
0HGLFDO0RQLWRU6$( &RQWDFW,QIRUPDWLRQ
Role
1DPH
'D\7LPH3KRQH1XPEHU
DQGHPDLODGGUHVV
$IWHUKRXUV
3KRQH&HOO

3DJHU
1XPEHU
)D[
1XPEH
U
6LWH$GGUHVV
3ULPDU\
0HGLFDO
0RQLWRU
&OLQLFDO
'HYHORSPHQ
W3K\VLFLDQ
5'
5HVSLUDWRU\
5	'
3KRQH
(PDLO

*OD[R6PLWK.OLQ
H5HVHDUFK	
'HYHORSPHQW
/LPLWHG
,URQ%ULGJH
5RDG
6WRFNOH\3DUN
:HVW8[EULGJH
0LGGOHVH[
8%%78.
6HFRQGDU\
0HGLFDO
0RQLWRU


0''
0HGLFDO
0RQLWRU
0'&*OREDO
&OLQLFDO'HY
± 865'
5HVSLUDWRU\
5	'
3KRQH
(PDLO

*OD[R6PLWK.OLQ
H5HVHDUFK	
'HYHORSPHQW
/LPLWHG
0RRUH'ULYH
32%R[
5731&

8QLWHG6WDWHV
6$(
FRRUGLQDWR
U


26/
3KRQH 
(PDLO
*6.)UDQFH
5RXWHGH
9HUVDLOOHV
0DUO\OH5RL
)UDQFH
6SRQVRU/HJDO5HJLVWHUHG$GGUHVV
*OD[R6PLWK.OLQH5HVHDUFK	'HYHORSPHQW/LPLWHG
*UHDW:HVW5RDG
%UHQWIRUG
0LGGOHVH[7:*6
8.

2017N339371_00
33'
33'
33'
33'
33'
33'
33'
33'
33'
3
3
'
33'
33'
33'
33'
33'
3
3
'

2014N190259_00
&21),'(17,$/
HZA116492
4
6SRQVRU&RQWDFW$GGUHVV
*OD[R6PLWK.OLQH5HVHDUFK	'HYHORSPHQW/LPLWHG
,URQ%ULGJH5RDG
6WRFNOH\3DUN:HVW8[EULGJH0LGGOHVH[8%%88.
7HOHSKRQH

6SRQVRU6HULRXV$GYHUVH(YHQWV6$(&RQWDFW,QIRUPDWLRQ
&DVH0DQDJHPHQW*URXS*&63
6WRFNOH\3DUN:HVW8[EULGJH0LGGOHVH[8%%88.
(PDLO
)D[
5HJXODWRU\$JHQF\,GHQWLI\LQJ1XPEHUV(XGUD&71R

2017N339371_00
33'
33'
33'

2014N190259_00
&21),'(17,$/
HZA116492
5
,19(67,*$72535272&2/$*5((0(173$*(
!
,FRQILUPDJUHHPHQWWRFRQGXFWWKHVWXG\LQFRPSOLDQFHZLWKWKHSURWRFRO
!
,DFNQRZOHGJHWKDW,DPUHVSRQVLEOHIRURYHUDOOVWXG\FRQGXFW,DJUHHWR
SHUVRQDOO\FRQGXFWRUVXSHUYLVHWKHGHVFULEHGVWXG\
!
,DJUHHWRHQVXUHWKDWDOODVVRFLDWHVFROOHDJXHVDQGHPSOR\HHVDVVLVWLQJLQWKH
FRQGXFWRIWKHVWXG\DUHLQIRUPHGDERXWWKHLUREOLJDWLRQV0HFKDQLVPVDUHLQ
SODFHWRHQVXUHWKDWVLWHVWDIIUHFHLYHV WKHDSSURSULDWHLQIRUPDWLRQWKURXJKRXWWKH
VWXG\
,QYHVWLJDWRU1DPHBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB
,QYHVWLJDWRU6LJQDWXUH
'DWH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
6
7$%/(2)&217(176
3$*(
1.
PROTOCOL SYNOPSIS FOR STUDY HZA116492.................................................9
2.
INTRODUCTION....................................................................................................14
2.1.
Study Rationale ..........................................................................................14
2.2.
Brief Background ........................................................................................15
3.
OBJECTIVE(S) AND ENDPOINT(S) ......................................................................16
4.
STUDY DESIGN ....................................................................................................18
4.1.
Overall Design ............................................................................................18
4.2.
Treatment arms and duration......................................................................21
4.3.
Type and Number of Subjects.....................................................................22
4.4.
Design Justification.....................................................................................22
4.5.
Dose Justification........................................................................................22
4.6.
Benefit:Risk Assessment ............................................................................23
4.6.1.
Risk Assessment .........................................................................24
4.6.1.1.
Benefit Assessment....................................................28
4.6.2.
Overall Benefit: Risk Conclusion..................................................28
5.
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA .............29
5.1.
Inclusion Criteria.........................................................................................29
5.2.
Exclusion Criteria........................................................................................31
5.3.
Screening/Baseline/Failures .......................................................................32
5.4.
Withdrawal/Stopping Criteria.......................................................................32
5.4.1.
Subjects Lost to Follow-up...........................................................32
5.4.2.
Subject Withdrawal by Investigator or Self-withdrawal .................32
5.4.3.
Liver Chemistry Stopping Criteria ................................................33
5.4.3.1.
Study Treatment Restart or Rechallenge....................35
5.4.4.
QTc Stopping Criteria ..................................................................35
5.5.
Subject and Study Completion....................................................................36
6.
STUDY TREATMENT ............................................................................................37
6.1.
Investigational Product and Other Study Treatment....................................37
6.2.
Medical Devices..........................................................................................38
6.3.
Treatment Assignment................................................................................38
6.4.
Planned Dose Adjustments.........................................................................39
6.5.
Blinding.......................................................................................................40
6.6.
Packaging and Labeling..............................................................................40
6.7.
Preparation/Handling/Storage/Accountability..............................................40
6.8.
Compliance with Study Treatment Administration.......................................41
6.9.
Treatment of Study Treatment Overdose....................................................41
6.10.
Treatment after the End of the Study ..........................................................41
6.11.
Concomitant Medications and Non-Drug Therapies....................................41
6.11.1.
Permitted Medications and Non-Drug Therapies..........................42
6.11.2.
Prohibited Medications and Non-Drug Therapies.........................42
7.
STUDY ASSESSMENTS AND PROCEDURES .....................................................42
7.1.
Time and Events Table...............................................................................43
7.2.
Screening and Critical Baseline Assessments ............................................44

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
7
7.3.
Efficacy.......................................................................................................45
7.3.1.
Inhaler Correct Use Assessment .................................................45
7.3.2.
Trough (pre-dose) FEV1 assessment ..........................................47
7.3.3.
Questionnaires ............................................................................48
7.3.3.1.
Asthma Control Test (ACT) ........................................48
7.3.3.2.
Asthma Quality of Life Questionnaire (AQLQ-S).........48
7.3.3.3.
EuroQol Questionnaire (EQ-5D)-5 Level ....................48
7.3.3.4.
Medication Adherence Report Scale for 
Asthma (MARS-A)......................................................48
7.3.3.5.
Patients Satisfaction and Preference with the 
device (PASAP Questionnaire)...................................49
7.4.
Safety .........................................................................................................49
7.4.1.
Adverse Events (AE), Adverse Drug Reactions (ADRs) 
and Serious Adverse Events (SAEs)............................................49
7.4.1.1.
Time period and Frequency for collecting non 
serious ADRs and SAE information............................49
7.4.1.2.
Method of Detecting non serious ADRs and 
SAEs ..........................................................................50
7.4.1.3.
Follow-up of non serious ADRs and SAEs..................50
7.4.1.4.
Cardiovascular and Death Events ..............................51
7.4.1.5.
Disease-Related Events and/or Disease-
Related Outcomes Not Qualifying as SAEs ................51
7.4.1.6.
Regulatory Reporting Requirements for SAEs............51
7.4.2.
Pregnancy ...................................................................................52
7.4.3.
Medical Device Incidents (Including Malfunctions).......................52
7.4.4.
Physical Exams ...........................................................................52
7.4.5.
Vital Signs....................................................................................52
7.4.6.
Electrocardiogram (ECG).............................................................53
7.4.7.
Clinical Safety Laboratory Assessments ......................................53
7.5.
Genetics .....................................................................................................53
8.
DATA MANAGEMENT ...........................................................................................53
9.
STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................53
9.1.
Hypotheses.................................................................................................53
9.2.
Sample Size Considerations.......................................................................54
9.2.1.
Sample Size Assumptions ...........................................................54
9.2.2.
Sample Size Sensitivity................................................................54
9.2.3.
Sample Size Re-estimation or Adjustment...................................55
9.3.
Data Analysis Considerations .....................................................................55
9.3.1.
Analysis Populations....................................................................55
9.3.2.
Interim Analysis ...........................................................................55
9.4.
Key Elements of Analysis Plan ...................................................................56
9.4.1.
Primary Analyses.........................................................................58
9.4.2.
Secondary Analyses ....................................................................60
9.4.3.
Other Analyses ............................................................................61
10. STUDY GOVERNANCE CONSIDERATIONS........................................................64
10.1.
Posting of Information on Publicly Available Clinical Trial Registers............64
10.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................64
10.3.
Quality Control (Study Monitoring) ..............................................................65

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
8
10.4.
Quality Assurance.......................................................................................65
10.5.
Study and Site Closure ...............................................................................66
10.6.
Records Retention......................................................................................66
10.7.
Provision of Study Results to Investigators, Posting of Information 
on Publically Available Clinical Trials Registers and Publication .................67
11. REFERENCES.......................................................................................................68
12. APPENDICES........................................................................................................70
12.1.
Appendix 1: Abbreviation and Trademarks .................................................70
12.2.
Appendix 2: Study Schematic .....................................................................72
12.3.
Appendix 3: Questionnaires........................................................................73
12.4.
Appendix 4: Liver Chemistry Stopping and Follow-up Criteria.....................76
12.5.
Appendix 5: Definition of and Procedures for Recording, Evaluating, 
Follow-Up and Reporting of Adverse Events...............................................79
12.5.1.
Definition of Adverse Events and ADRs.......................................79
12.5.2.
Definition of Serious Adverse Events...........................................80
12.5.3.
Definition of Cardiovascular Events .............................................81
12.5.4.
Recording of AEs (ADRs) and SAEs............................................82
12.5.5.
Evaluating AEs (ADRs) and SAEs ...............................................83
12.5.6.
Reporting of SAEs to GSK...........................................................84
12.6.
Appendix 6: Genetic Research ...................................................................85
12.7.
Appendix 7: Collection of Pregnancy Information........................................88

2017N339371_00

2014N190259_00 
CONFIDENTIAL 
 
 
 
HZA116492
 9
 
 
1.  
PROTOCOL SYNOPSIS FOR STUDY HZA116492 
Rationale 
The  pivotal  phase  III  studies were  key  to  demonstrate  the  safety  and  efficacy  of 
Fluticasone Furoate/ Vilanterol in asthma. However, it is increasingly acknowledged that 
randomised  clinical  trials  by  definition  tend to  be  highly  controlled  and  enrol  a  more 
highly selected patient population than is expected to be prescribed the medication post-
approval. The need for data in a more representative population in a close to ‘real world’ 
setting  is  increasingly  being recognised  as  important  to complement  pivotal  phase  III 
safety and efficacy studies in order to establish the benefits and therefore the value of a 
medication in the context of clinical practice.  
Moreover,  double-blind  comparison  of  once  daily  to  twice  daily  medicines,  while 
important for assessing efficacy, removes a potential source of difference in effectiveness 
derived from patient behaviour and experience. GlaxoSmithKline (GSK) has observed an 
increasing demand from payers who make reimbursement and policy decisions for data 
that enables the evaluation of a drug
's effectiveness and impact on the health care system 
at  launch,  e.g.  effectiveness  data  from  a  setting  close  to 
 'real  world
'  in  addition  to 
traditional randomised clinical studies. 
This open-label randomised clinical study will evaluate the efficacy and safety of FF/VI 
Inhalation  Powder  
(FF  92mcg/VI  22mcg  or  FF  184mcg/VI  22mcg)  compared  with  
two 
fixed  combinations  ICS/LABA  (Inhaled  Corticosteroids/Long  Acting  Beta  Agonists) 
inhalation powders, fluticasone propionate/salmeterol (FP/S) and budesonide/formoterol 
(BUD/F),  for  asthma  maintenance  therapy,  in a  “close  to  real  life”  manner  in  French 
primary and respiratory specialist care. FF/VI will be administered once-daily (QD) via 
Ellipta™ and FP/S or BUD/F twice daily (BID) via Diskus™ and Turbuhaler respectively. 
 
Objective(s)/Endpoint(s) 
Objectives
 Endpoints 
Primary 
• To compare the efficacy of FF/VI 
92mcg/ 22mcg or FF 184mcg/22mcg 
with usual fixed combinations 
ICS/LABA for asthma maintenance 
therapy at Week 12 (Visit 4). 
• Change from baseline in the Asthma 
Control Test (ACT) total score at Week 
12 (Visit 4). 
Secondary 
 
• To assess effect of FF/VI on asthma 
control compared with usual ICS/LABA 
fixed combination at Week 24 (Visit 6). 
• To assess ELLIPTA™ inhaler correct use 
compared with other DPI (Diskus
™ and 
Turbuhaler) at Week 12 (Visit 4) and at 
Week 24 (Visit 6) independently of the 
 
• Change from baseline in ACT score at 
Week 24 (Visit 6). 
 
• Percentage of subjects making at least 1 
Type A error (likely to be critical) and 
overall errors at Week 12 (Visit 4) and 
at Week 24 (Visit 6) independently of 
 
2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
10
Objectives
Endpoints
XVHDW:HHN9LVLW
WKHXVHDW:HHN  9LVLW
Other
!
7RDVVHVVHIIHFWRI))9,RQWURXJK SUH
GRVH )(9FRPSDUHGZLWKXVXDO
,&6/$%$IL[HG FRPELQDWLRQDW:HHN
9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQ
UHVSRQVHWRWUHDWPHQW DW:HHN9LVLW
DQG:HHN 9LVLW
!
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQ DW:HHN9LVLWDQG
:HHN 9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQ RYHUWKHVWXG\
SHULRG
!
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIH DW:HHN
9LVLW
!
&KDQJHIURPEDVHOLQHLQWURXJKSUH
GRVH)(9DW:HHN9LVLW
!
$&7VFRUH RUSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7 DW:HHN 
9LVLWDQG:HHN  9LVLW 1RWH
$SRLQWLQFUHDVHLQ$&7WRWDOVFRUH
ZDVVXJJHVWHGDVWKH0LQLPDO
&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]
@
!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN
9LVLWDQG:HHN 9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
!
1XPEHURIVXEMHFWZLWKDWOHDVW
VHYHUHDVWKPDH[DFHUEDWLRQQXPEHU
RIVHYHUHDVWKPDH[DFHUEDWLRQDQG
DQQXDOVHYHUHH[DFHUEDWLRQUDWHRYHU
WKH VWXG\SHULRG
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUH DW:HHN
 9LVLW
!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4VWRWDOVFRUHDW:HHN  9LVLW

!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4V
HQYLURQPHQWDO
VWLPXOL
GRPDLQVFRUHDW:HHN 9LVLW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
11
Objectives
Endpoints
!
7RDVVHVV3DWLHQW6DWLVIDFWLRQ DQG
3UHIHUHQFH DVVHVVPHQW ZLWKGLIIHUHQW
LQKDOHUV DW:HHN 9LVLW
!
7RHYDOXDWHWKH6DIHW\RI))9,
FRPSDUHGZLWKXVXDO,&6/$%$)36
DQG%XG)
!
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVH IURP EDVHOLQH RI   LQ
$4/46 ,QGLYLGXDO GRPDLQVFRUHV DW
:HHN 9LVLW
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
!
+HDOWK VWDWXV XVLQJ WKH (XUR4RO
4XHVWLRQQDLUH (4' DW :HHN 
9LVLW
!
6FRUHRI3$6$3 4XHVWLRQQDLUH 3DWLHQW
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN
 9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
!
)UHTXHQF\ DQG W\SH RI VHULRXV
DGYHUVHHYHQWV
!
)UHTXHQF\DQGW\SHRIQRQVHULRXV
DGYHUVH GUXJ UHDFWLRQV UHODWHG WR
WUHDWPHQW
$VHYHUHDVWKPDH[DFHUEDWLRQZLOOEHGHILQHGDVGHWHULRUDWLRQRIDVWKPDUHTXLULQJWKH
XVHRIV\VWHPLFFRUWLFRVWHURLGV WDEOHWVVXVSHQVLRQRULQMHFWLRQIRUDWOHDVWGD\VRUDQ
LQSDWLHQW KRVSLWDOLVDWLRQ RU HPHUJHQF\ GHSDUWPHQW YLVLW GXH WR DVWKPD WKDW UHTXLUHG
V\VWHPLFFRUWLFRVWHURLGV 
1RWHVGHILQLQJHQGSRLQWV
 &RQWDFWV ZLWK D GRFWRU RU KRVSLWDOLVDWLRQ DUH GHILQHG DV H[DFHUEDWLRQUHODWHG
FRQWDFWV LI WKHVH FRQWDFWV ZHUH D GLUHFW UHVXOW RI DQ DFXWH ZRUVHQLQJ RI DVWKPD
V\PSWRPV
 $SUHVFULSWLRQRIV\VWHPLFFRUWLFRVWHURLGLVGHILQHGDVH[DFHUEDWLRQUHODWHGLIWKH
UHDVRQWKHGUXJZDVJLYHQLQZKROHRULQSDUWZDVWRWUHDWDQDFXWHZRUVHQLQJRI
DVWKPDV\PSWRPV

([DFHUEDWLRQUHODWHGKRVSLWDOLVDWLRQLQFOXGHVKRVSLWDOLVDWLRQWKDWLVSURORQJHGDVD
UHVXOWRIDQDVWKPDH[DFHUEDWLRQ

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
12
2YHUDOO'HVLJQ
7KLVLVD3KDVH,,,EPXOWLFHQWUHUDQGRPLVHGRSHQODEHOSDUDOOHOJURXS VWXG\SHUIRUPHG
LQVXEMHFWVLQSULPDU\DQGUHVSLUDWRU\VSHFLDOLVWFDUHZKRKDYHDGLDJQRVLVRIDVWKPDDQG
UHJXODUWUHDWPHQWIRU DVWKPDLQ)UDQFH
$SSUR[LPDWHO\  DVWKPDWLF VXEMHFWV ZKR DUH WDNLQJ DQ LQKDOHG FRUWLFRVWHURLG ,&6
DORQHZLWKRXWDQ\RWKHUFRQWUROOHUWUHDWPHQWZLOOEHUDQGRPLVHGLQDUDWLRWRUHFHLYH
HLWKHU ))9, ))9, PFJPFJ RU ))9, PFJPFJ RQFH GDLO\ RU RQH
,&6/$%$ LQKDODWLRQSRZGHUWZLFHGDLO\IRUDVWKPDPDLQWHQDQFHWKHUDS\
$VPXFKDVSRVVLEOHHQUROPHQWRIVXEMHFWVVKRXOGEHSHUIRUPHGDWDFRQVWDQWDFFUXDOUDWH
WKURXJKRXWDIXOO\HDULQRUGHUWRPLQLPL]HDVHDVRQDOLW\ELDV
6XEMHFWVZLOOYLVLWWKH+&3JHQHUDOSUDFWLWLRQHURUSXOPRQRORJLVWDPLQLPXPRIWLPHV
DVSHUSURWRFRORYHUDPRQWKSHULRGZKLOHSDUWLFLSDWLQJLQWKHVWXG\7KHILUVWYLVLWZLOO
EH9LVLW 6FUHHQLQJ9LVLWZKLFKFDQWDNHSODFHEHWZHHQ'D\DQG'D\$W9LVLW
VXLWDEOH VXEMHFWV ZLOO EH FRQVHQWHG 7KH VHFRQG YLVLW ZLOO EH 9LVLW  'D\ 
5DQGRPLVDWLRQ9LVLWZKHUHVXEMHFWVZKRPHHWDOORIWKH,QFOXVLRQ&ULWHULDDQGQRQHRI
WKH([FOXVLRQ&ULWHULDZLOOEHUDQGRPLVHG9LVLWDQG9LVLWFDQEHFRPELQHGLIWKH
VXEMHFWGLGQRWWDNHKLVXVXDODVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG
9LVLWDUHFRPELQHGWKHQWKLVYLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEH
FROOHFWHGDWWKLVYLVLW
$W9LVLW'D\VXEMHFWZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4
'DQG0$56$TXHVWLRQQDLUHV%DVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6. $WOHDVWWKUHHYDOLGDVVHVVPHQWV
VKRXOG EH SHUIRUPHG ZLWK UHJLVWUDWLRQ RI WKH EHVW YDOXH 2Q WKH PRUQLQJ RI 9LVLW 
VXEMHFWVZLOOQRWWDNHWKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOO
EHVWRSSHGKRXUVEHIRUHEDVHOLQHVSLURPHWU\
6XEMHFWVZLOOVHOIDGPLQLVWHUWKHLUILUVWGRVHRIVWXG\GUXJLQWKHFOLQLFDW9LVLWRUWKH
FRPELQHG9LVLWDQG9LVLWLIDSSURSULDWHXQGHUVXSHUYLVLRQRIWKHVLWHVWDII
7KHUHDIWHU HDFK VXEMHFW UDQGRPLVHG LQWR WKH ))9, DUP ZLOO EH LQVWUXFWHG WR VHOI
DGPLQLVWHURQHLQKDODWLRQZLWK(OOLSWD LQKDOHUHDFKGD\DWWKHVDPHWLPHRIWKHGD\DWD
WLPHWKDWLVFRQYHQLHQWIRUWKHVXEMHFW(DFKVXEMHFWZLOOEHDGYLVHGWRDGKHUHWR))9,
GRVLQJ UHJLPHQ WKURXJKRXW WKH VWXG\ 7KH LQYHVWLJDWRU PD\ DGMXVW WKH GRVH RI ))9,
DFFRUGLQJWRWKHVXEMHFW¶VUHVSRQVH'RVHDGMXVWPHQWLVDOORZHG DQGLVQRWFRQVLGHUHGDV
DWUHDWPHQWIDLOXUHLQDFFRUGDQFHZLWKWUHDWPHQWIDLOXUHGHILQLWLRQ
,Q DGGLWLRQ HDFK VXEMHFW ZKRVH ))9, (OOLSWD IRU DVWKPD PDLQWHQDQFH WKHUDS\ LV
LQLWLDWHGDW9LVLWZLOOEHDVNHGWRUHDGWKHLQIRUPDWLRQOHDIOHWDQGZLOOEH LQVWUXFWHGE\
WKHLQYHVWLJDWRURQWKHSURSHUXVHRI(OOLSWD(DFKVXEMHFWZKRVHXVXDO,&6/$%$'3,
'LVNXV RU7XUEXKDOHUIRUDVWKPDPDLQWHQDQFHWKHUDS\LVLQLWLDWHGDW9LVLWZLOOIROORZ
WKHVDPHSURFHGXUHUHDGLQJRIWKHLQIRUPDWLRQOHDIOHWGHPRQVWUDWLRQRIWKHSURSHUXVHRI
WKH LQKDOHUV E\ WKH ,QYHVWLJDWRU DQG WKH FRUUHFW GRVLQJ 7KLV ZLOO EH IROORZHG E\ DQ
LQKDODWLRQGHPRQVWUDWLRQE\WKHSDWLHQW$Q\PLVWDNHV7\SH$HUURUVFRUUHVSRQGLQJWR

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
13
FULWLFDOHUURUVDQGRYHUDOOHUURUVZLOOEHUHJLVWHUHGE\WKH,QYHVWLJDWRU )RUWKHGHILQLWLRQ
RI7\SH$HUURUVDQGRYHUDOOHUURUVVHH6HFWLRQ
5DQGRPLVDWLRQDWWKLVYLVLWZLOO EHSHUIRUPHGRQDEDVLVWRWKH ))9,IL[HGGRVH
FRPELQDWLRQ GHOLYHUHG YLD (OOLSWD RU WKH LQLWLDWLRQ ZLWK XVXDO ,&6/$%$ LQKDODWLRQ
SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\
$W:HHN 9LVLWDQGDW:HHN9LVLWVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXW
ZKHWKHUWKH VXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQVHULRXVDGYHUVH
GUXJUHDFWLRQV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWH WKH$&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW 6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLWVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG3$6$3TXHVWLRQQDLUHVDQGWKHLQKDOHUXVHZLOOEHDVVHVVHGE\UHFRUGLQJ7\SH$
HUURUVDQGRYHUDOOHUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLW DWURXJK SUHGRVH)(9ZLOOEH
DVVHVVHGE\WKH,QYHVWLJDWRUXVLQJ D VSLURPHWHUSURYLGHGE\*6.DQGVXEMHFWVZLOODOVR
EHLQWHUYLHZHGDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRU
QRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVR
EHUHPLQGHGDERXWWKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHVZLOOEHFRQGXFWHGDWWKLVYLVLWDQG7\SH$HUURUVDQGRYHUDOOHUURUVZLWK
LQKDOHUZLOOEHUHFRUGHGIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ$WWKLVYLVLWVXEMHFWVZLOODOVREHLQWHUYLHZHGDERXW
ZKHWKHUWKH\KDGH[SHULHQFHGDQ\VHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJ
UHDFWLRQV7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKH
VDPHWLPHRIWKHGD\DV 9LVLW
$OWKRXJKDWOHDVWIRUPDOVFKHGXOHGYLVLWVDQGSKRQHFDOOVDUHSODQQHGIRUWKLVVWXG\
VXEMHFWVVKRXOGFRQWLQXHWRYLVLWWKHLUSK\VLFLDQIRUDQ\URXWLQHQDWXUDOLVWLFYLVLWVDVSHU
QRUPDO FOLQLFDO SUDFWLFH DV SHU WKH 7LPH DQG (YHQWV 7DEOH 6HFWLRQ  $Q (DUO\
:LWKGUDZDO9LVLWKDVWREHFRQVLGHUHGLQFDVHRIHDUO\ZLWKGUDZDORIWKHVXEMHFWIURPWKH
VWXG\DVSHUWKH7LPHDQG(YHQWV7DEOH6HFWLRQ
7UHDWPHQW$UPVDQG'XUDWLRQ
7ZRWUHDWPHQWDUPVRQH))9,DUP))9,PFJPFJRU))9,PFJPFJ
RQFHGDLO\DQGRQHDUP,&6/$%$FRPELQDWLRQWKHUDS\LQLQKDODWLRQSRZGHU WZLFH
GDLO\)36PFJPFJRU PFJPFJRU%8')PFJPFJRU
PFJPFJDVGHFLGHGE\WKHSK\VLFLDQ 7KHWRWDOGXUDWLRQRIVXEMHFWSDUWLFLSDWLRQZLOO
EHDSSUR[LPDWHO\PRQWKVZHHNV

2017N339371_00

2014N190259_00 
&21),'(17,$/
 
 
 
HZA116492 
 
14 
 
7\SHDQG1XPEHURI6XEMHFWV
6XEMHFWV ZLWK GRFXPHQWHG SK\VLFLDQ¶V GLDJQRVLV RI DVWKPD   \HDU XQVDWLVIDFWRULO\
FRQWUROOHG DVWKPD $&7   WUHDWHG E\ ,&6 DORQH DQG LQWHQGHG WR EH WUHDWHG E\
,&6/$%$ PDLQWHQDQFH WKHUDS\ $ VXEMHFW ZLOO EH HOLJLEOH IRU LQFOXVLRQ LQ WKLV VWXG\
RQO\LIHLWKHUDIILOLDWHGWRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURIUDQGRPLVHGVXEMHFWVVRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDRIVFUHHQIDLOXUHVXEMHFWVZLOOKDYHWREHVFUHHQHGLQWKHVWXG\ZLWK
VXEMHFWVFHQWHU
$QDO\VLV
7KH SULPDU\ HQGSRLQW LV GHILQHG DV WKH FKDQJH IURP EDVHOLQH LQ WKH $&7 WRWDO VFRUH
DVVHVVHGDW:HHN9LVLW7KHSULPDU\VHWRIDQDO\VLVLVWKH,77VHW
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHWZRVLGHGQRPLQDO
OHYHORIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,
WR,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH

,1752'8&7,21

6WXG\5DWLRQDOH
,QKDOHG FRUWLFRVWHURLGV ,&6 DUH FRQVLGHUHG WKH PRVW HIIHFWLYH DQWLLQIODPPDWRU\
WUHDWPHQWV IRU DOO VHYHULWLHV RI SHUVLVWHQW DVWKPD 7KLV RSHQODEHO UDQGRPLVHG FOLQLFDO
VWXG\ ZLOO HYDOXDWH WKH HIILFDF\ DQG VDIHW\ RI IOXWLFDVRQH IXURDWH ))YLODQWHURO 9,
,QKDODWLRQ 3RZGHU FRPSDUHG ZLWK H[LVWLQJ IL[HG FRPELQDWLRQV ,&6/$%$ ,QKDOHG
&RUWLFRVWHURLGV/RQJ$FWLQJ%HWD$JRQLVWVLQKDODWLRQSRZGHUV
)OXWLFDVRQHIXURDWH))LVD JOXFRFRUWLFRLGGHYHORSHGIRUXVHDVDRQFHGDLO\LQKDOHG
WUHDWPHQW IRU DVWKPD 9LODQWHURO LV DQ RUDOO\ LQKDOHG ORQJDFWLQJ DJRQLVW RI WKH EHWD
DGUHQRFHSWRU/$%$DQGKDVEHHQDOVRGHYHORSHGIRUXVHLQFRPELQDWLRQZLWK,&6DVD
RQFHGDLO\PDLQWHQDQFHWUHDWPHQWRIDVWKPD
7KHSLYRWDOSKDVH,,,VWXGLHVGHPRQVWUDWHGWKHVDIHW\DQGHIILFDF\RI))9,+RZHYHULW
LV LQFUHDVLQJO\ DFNQRZOHGJHG WKDW UDQGRPLVHG FOLQLFDO WULDOV E\ GHILQLWLRQ WHQG WR EH
KLJKO\FRQWUROOHGDQGHQURODPRUHKLJKO\VHOHFWHGSDWLHQWSRSXODWLRQWKDQLVH[SHFWHGWR
EHSUHVFULEHGWKHPHGLFDWLRQSRVWDSSURYDO7KHQHHGIRUGDWDLQDPRUHUHSUHVHQWDWLYH
SRSXODWLRQLQFORVHWRDµUHDOZRUOG¶VHWWLQJLVLQFUHDVLQJO\EHLQJUHFRJQLVHGDVLPSRUWDQW
WR FRPSOHPHQW SLYRWDO SKDVH ,,, VDIHW\ DQG HIILFDF\ VWXGLHV LQ RUGHU WR HVWDEOLVK WKH
EHQHILWVDQGWKHUHIRUHWKHYDOXHRIDPHGLFDWLRQLQWKHFRQWH[WRIFOLQLFDOSUDFWLFH,QGHHG
LQ WKH FORVH WR µUHDO OLIH¶ FRQGLWLRQV SK\VLFLDQV KDYH WKH DELOLW\ WR FKRRVH WKH EHVW
WUHDWPHQW LQ WKHLU YLHZ IRU DQ\ LQGLYLGXDO SDWLHQW DQG DGDSW WUHDWPHQWV WR VXEMHFWV¶
FKDUDFWHULVWLFVDQGUHVSRQVH7KXVGRXEOHEOLQGFRPSDULVRQRIRQFHGDLO\WRWZLFHGDLO\
PHGLFLQHV ZKLOH LPSRUWDQW IRU DVVHVVLQJ HIILFDF\ UHPRYHV D SRWHQWLDO VRXUFH RI
GLIIHUHQFHLQHIIHFWLYHQHVVGHULYHGIURPSDWLHQWEHKDYLRXUDQGH[SHULHQFH0RUHRYHUD
KHDGWRKHDG VWXG\ FRPSDULQJ 5HOYDU PFJPFJ (OOLSWD ))9, RQFH D GD\ YV

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
15
6HUHWLGH PFJPFJ'LVNXV )OXWLFDVRQH SURSLRQDWHVDOPHWHURO WZLFHDGD\IDLOHG
WRGHPRQVWUDWHVXSHULRULW\RQKRXUVZHLJKWHGPHDQ)(9DIWHU PRQWKVRIWUHDWPHQW
+RZHYHU  RI VXEMHFWV LQ ERWK DUPV ZHUH XQFRQWUROOHG $&7 VFRUH   DW
UDQGRPLVDWLRQDIWHU ZHHNVRI)OXWLFDVRQHSURSLRQDWHPFJWZLFHDGD\)RUWKLV
VXEJURXSRIVXEMHFWVDWWKHHQGRIWKHPRQWKWUHDWPHQWSHULRGRI VXEMHFWVZHUH
FRQWUROOHGLQWKH))9, DUPYVLQWKH6HUHWLGH 'LVNXV  DUP7KHVWXG\ZDVQRW
SRZHUHGRQWKLVFULWHULRQQRUGHVLJQHGWRLQFOXGHXQFRQWUROOHGVXEMHFWVRQO\$Q\ZD\
WKLVWUHQGMXVWLILHVH[SORULQJLIWKLVGLIIHUHQFHZRXOGGLVDSSHDURULQFUHDVHLQDFORVHWR
UHDOOLIHVHWWLQJ
6XEMHFWVUHFUXLWHGLQWRWKHVWXG\ZLOOEHWKRVHFXUUHQWO\WDNLQJDQ,&6DORQHZLWKRXWDQ\
RWKHUFRQWUROOHUWUHDWPHQWZLWKHYLGHQFHRIVXERSWLPDODVWKPDFRQWUROFRUUHVSRQGLQJWR
(XURSHDQ 0DUNHWLQJ $XWKRULVDWLRQ RI ))9, 7KHVH VXEMHFWV ZLOO EH UDQGRPLVHG WR
UHFHLYH ))9, YLD (OOLSWD LQKDOHU RQFH GDLO\ RU WR UHFHLYH XVXDO ,&6/$%$ IL[HG
FRPELQDWLRQ LQ '3, IOXWLFDVRQH SURSLRQDWHVDOPHWHURO )36 YLD 'LVNXV LQKDOHU DQG
EXGHVRQLGHIRUPRWHURO %8') YLD 7XUEXKDOHU WZLFH GDLO\ IRU DVWKPD PDLQWHQDQFH
WKHUDS\DVSHUQRUPDOFOLQLFDOSUDFWLFH (OOLSWD LVDQHZSRZGHULQKDOHUGHVLJQHGWREH
HDV\WRXVH&XUUHQWSRZGHULQKDOHUVKDYHEHHQDVVRFLDWHGZLWKKDQGOLQJHUURUVVRPHRI
ZKLFKPD\LPSDFWWKHDELOLW\RIGUXJWRUHDFKWKHOXQJDQGKHQFHLPSDFWFOLQLFDOHIILFDF\
6XFKHUURUVGHHPHGDVFULWLFDOZLOOEHHYDOXDWHGLQWKLVVWXG\EHWZHHQGLIIHUHQWLQKDOHUV
DVZHOODVRYHUDOOLQKDOHUSUHIHUHQFHDQGVDWLVIDFWLRQ

%ULHI%DFNJURXQG
$VWKPD LV D FKURQLF GLVHDVH RI WKH OXQJV FKDUDFWHULVHG E\ DLUZD\ LQIODPPDWLRQ
EURQFKRFRQVWULFWLRQDQGLQFUHDVHGDLUZD\UHVSRQVLYHQHVV ,QKDOHGFRUWLFRVWHURLGV,&6
DUH FRQVLGHUHG WKH PRVW HIIHFWLYH DQWLLQIODPPDWRU\ WUHDWPHQWV IRU DOO VHYHULWLHV RI
SHUVLVWHQWDVWKPD>*,1$1,+%ULWLVK7KRUDFLF6RFLHW\@ 7KHEHQHILWV
RI,&6LQFOXGHFRQWURORIDVWKPDV\PSWRPVLPSURYHPHQWLQOXQJIXQFWLRQGHFUHDVHLQ
DLUZD\ K\SHUUHVSRQVLYHQHVV DQG SRVVLEO\ SUHYHQWLRQ RI DLUZD\ ZDOO UHPRGHOOLQJ
>3HGHUVHQ)DQWD@
)OXWLFDVRQHIXURDWHLVDQRYHOJOXFRFRUWLFRLGGHYHORSHG IRUXVHDVDRQFHGDLO\LQKDOHG
WUHDWPHQWIRUDVWKPD7KHGUXJFRQVLVWVRI))IRUPXODWHGLQODFWRVHIRURUDOLQKDODWLRQYLD
WKH'3,(OOLSWD3UHFOLQLFDOGDWDDQGHDUO\SKDVHFOLQLFDOVWXGLHVLQGLFDWHWKDW))KDVD
ORQJHUGXUDWLRQRIDFWLRQWKDQIOXWLFDVRQHSURSLRQDWH)3 DQGLVWKHUHIRUHVXLWDEOHIRU
GHYHORSPHQWIRURQFHGDLO\DGPLQLVWUDWLRQ
9LODQWHUROLVDQRUDOO\LQKDOHGORQJDFWLQJDJRQLVWRIWKHEHWDDGUHQRFHSWRU/$%$DQG
KDV EHHQ GHYHORSHG IRU XVH LQ FRPELQDWLRQ ZLWK ,&6 DV D RQFHGDLO\ PDLQWHQDQFH
WUHDWPHQWRIDVWKPD7KHGUXJFRQVLVWVRIYLODQWHUROIRUPXODWHGLQODFWRVHDQGPDJQHVLXP
VWHDUDWHIRURUDOLQKDODWLRQYLD(OOLSWD
7KHFRPELQDWLRQRIWKHVHWZRDJHQWVKDVEHHQGHYHORSHGDVDRQFHGDLO\ FRPELQDWLRQ
WKHUDS\IRUWKHORQJWHUPPDLQWHQDQFHWUHDWPHQWRIDVWKPDLQDGXOWVDQGFKLOGUHQ∀
\HDUV RI DJH 7KH DYDLODELOLW\ RI D RQFHGDLO\ ,&6 FRPELQHG ZLWK D /$%$ ZRXOG EH
H[SHFWHGWRKHOSWRLPSURYHFRPSOLDQFHDQGWKHUHIRUHLPSURYHDVWKPDFRQWURO

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
16
,QIRUPDWLRQ RQ WKH SK\VLFDO FKHPLFDO DQG SKDUPDFHXWLFDO SURSHUWLHV RI IOXWLFDVRQH
IXURDWH YLODQWHURO DQG IOXWLFDVRQH IXURDWHYLODQWHURO PD\ EH IRXQG LQ 6P3& RU
,QYHVWLJDWRU%URFKXUH

2%-(&7,9(6 $1'(1'32,176
7KLV RSHQODEHO UDQGRPLVHG FOLQLFDO VWXG\ ZLOO HYDOXDWH WKH HIILFDF\ DQG VDIHW\ RI
IOXWLFDVRQHIXURDWH))YLODQWHURO9, ,QKDODWLRQ3RZGHU))PFJ9,PFJRU ))
PFJ9, PFJ FRPSDUHG ZLWK H[LVWLQJ IL[HG FRPELQDWLRQV ,&6/$%$ ,QKDOHG
&RUWLFRVWHURLGV/RQJ
$FWLQJ
%HWD
$JRQLVWV
LQKDODWLRQ
SRZGHUV
IOXWLFDVRQH
SURSLRQDWHVDOPHWHURO )36 DQG EXGHVRQLGHIRUPRWHURO %8') IRU
DVWKPD
PDLQWHQDQFHWKHUDS\LQD³FORVHWRUHDOOLIH´PDQQHULQ)UHQFKSULPDU\DQGUHVSLUDWRU\
VSHFLDOLVW FDUH ))9, ZLOO EH DGPLQLVWHUHG RQFHGDLO\ 4' YLD (OOLSWD DQG )36 RU
%8')WZLFHGDLO\%,'YLD'LVNXV DQG7XUEXKDOHUUHVSHFWLYHO\
Objectives
Endpoints
Primary
!
7RFRPSDUHWKHHIILFDF\RI))9,
PFJPFJRU))PFJPFJ
ZLWKXVXDOIL[HGFRPELQDWLRQV
,&6/$%$IRUDVWKPDPDLQWHQDQFH
WKHUDS\DW:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQWKH$VWKPD
&RQWURO7HVW$&7WRWDOVFRUHDW:HHN
9LVLW
Secondary
!
7RDVVHVVHIIHFWRI))9,RQDVWKPD
FRQWUROFRPSDUHGZLWKXVXDO,&6/$%$
IL[HGFRPELQDWLRQDW:HHN9LVLW
!
7RDVVHVV(//,37$ LQKDOHUFRUUHFWXVH
FRPSDUHGZLWKRWKHU'3,'LVNXV DQG
7XUEXKDOHUDW:HHN9LVLWDQGDW
:HHN9LVLWLQGHSHQGHQWO\RIWKH
XVHDW:HHN 9LVLW
!
&KDQJHIURPEDVHOLQHLQ$&7VFRUHDW
:HHN9LVLW
!
3HUFHQWDJHRIVXEMHFWVPDNLQJDWOHDVW
7\SH$HUURUOLNHO\WREHFULWLFDODQG
RYHUDOOHUURUVDW:HHN9LVLWDQG
DW:HHN 9LVLW LQGHSHQGHQWO\RI
WKHXVHDW:HHN 9LVLW
Other
!
7RDVVHVVHIIHFWRI))9,RQSUHGRVH
WURXJK)(9FRPSDUHGZLWKXVXDO
,&6/$%$IL[HGFRPELQDWLRQDW:HHN
9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQ
UHVSRQVHWRWUHDWPHQWDW:HHN9LVLW
DQG:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQSUHGRVH
WURXJK)(9DW:HHN9LVLW
!
$&7VFRUHRUSRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7DW:HHN
9LVLWDQG:HHN9LVLW1RWH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
17
Objectives
Endpoints
!
7RDVVHVVWKHDGKHUHQFHZLWKVWXG\
PHGLFDWLRQDW:HHN9LVLWDQG
:HHN9LVLW
!
7RDVVHVVWKHHIIHFWRI))9,RQVHYHUH
DVWKPDH[DFHUEDWLRQRYHUWKH VWXG\
SHULRG
!
7RDVVHVVWKHHIIHFWRI))9,RQ+HDOWK
5HODWHG4XDOLW\RI/LIHDW:HHN
9LVLW
$SRLQWLQFUHDVHLQ$&7WRWDOVFRUH
ZDVVXJJHVWHGDVWKH0LQLPDO
&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
0&,'LQWKHOLWHUDWXUH>6FKDW]
@
!
1XPEHU RI PHGLFDWLRQV GLVSHQVHG DQG
FROOHFWHG GXULQJ WKH VWXG\ DW :HHN 
9LVLWDQG:HHN9LVLW
!
6FRUH RI WKH 0$56$ TXHVWLRQQDLUH
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHDW
WKH UDQGRPLVDWLRQ 'D\ :HHN
9LVLWDQG:HHN9LVLW
!
1XPEHURIVXEMHFWZLWKDWOHDVW
VHYHUHDVWKPDH[DFHUEDWLRQQXPEHU
RIVHYHUHDVWKPDH[DFHUEDWLRQDQG
DQQXDOVHYHUHH[DFHUEDWLRQUDWHRYHU
WKH VWXG\SHULRG
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQ VFRUHV RI $4/46 $VWKPD
4XDOLW\RI/LIH4XHVWLRQQDLUHDW:HHN
9LVLW
!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4VWRWDOVFRUHDW:HHN9LVLW

!
$Q LQFUHDVH IURPEDVHOLQHRI LQ
$4/4V
HQYLURQPHQWDO
VWLPXOL
GRPDLQVFRUH DW:HHN9LVLW
!
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ
LQFUHDVH IURP EDVHOLQH RI   LQ
$4/46 ,QGLYLGXDO GRPDLQVFRUHV DW
:HHN9LVLW
!
&KDQJHIURPEDVHOLQHLQWRWDOVFRUHDQG
GRPDLQVFRUHVRI$4/46DW:HHN
9LVLW
!
+HDOWK VWDWXV XVLQJ WKH (XUR4RO
4XHVWLRQQDLUH (4' DW :HHN 
9LVLW
!
6FRUHRI3$6$34XHVWLRQQDLUH3DWLHQW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
18
Objectives
Endpoints
!
7RDVVHVV3DWLHQW6DWLVIDFWLRQDQG
3UHIHUHQFHDVVHVVPHQWZLWKGLIIHUHQW
LQKDOHUV DW:HHN9LVLW
!
7RHYDOXDWHWKH6DIHW\RI))9,
FRPSDUHGZLWKXVXDO,&6/$%$)36
DQG%XG)
6DWLVIDFWLRQ DQG 3UHIHUHQFH DW :HHN
9LVLW
6HULRXV$GYHUVH(YHQWV6$(DQGQRQ
VHULRXV$GYHUVH'UXJ5HDFWLRQV$'5
!
)UHTXHQF\ DQG W\SH RI VHULRXV
DGYHUVHHYHQWV
!
)UHTXHQF\DQGW\SHRIQRQVHULRXV
DGYHUVH GUXJ UHDFWLRQV UHODWHG WR
WUHDWPHQW
$VHYHUHDVWKPDH[DFHUEDWLRQZLOOEHGHILQHGDVGHWHULRUDWLRQRIDVWKPDUHTXLULQJWKH
XVHRIV\VWHPLFFRUWLFRVWHURLGV WDEOHWVVXVSHQVLRQRULQMHFWLRQIRUDWOHDVWGD\V RUDQ
LQSDWLHQW KRVSLWDOLVDWLRQ RU HPHUJHQF\ GHSDUWPHQW YLVLW GXH WR DVWKPD WKDW UHTXLUHG
V\VWHPLFFRUWLFRVWHURLGV 
1RWHVGHILQLQJHQGSRLQWV
 &RQWDFWV ZLWK D GRFWRU RU KRVSLWDOLVDWLRQ DUH GHILQHG DV H[DFHUEDWLRQUHODWHG
FRQWDFWV LI WKHVH FRQWDFWV ZHUH D GLUHFW UHVXOW RI DQ DFXWH ZRUVHQLQJ RI DVWKPD
V\PSWRPV
 $SUHVFULSWLRQRIV\VWHPLFFRUWLFRVWHURLGLVGHILQHGDVH[DFHUEDWLRQUHODWHGLIWKH
UHDVRQWKHGUXJZDVJLYHQLQZKROHRULQSDUWZDVWRWUHDWDQDFXWHZRUVHQLQJRI
DVWKPDV\PSWRPV

([DFHUEDWLRQUHODWHGKRVSLWDOLVDWLRQLQFOXGHVKRVSLWDOLVDWLRQWKDWLVSURORQJHGDVD
UHVXOWRIDQDVWKPDH[DFHUEDWLRQ

678'<'(6,*1

2YHUDOO'HVLJQ
7KLVLVD3KDVH,,,EPXOWLFHQWHUUDQGRPLVHGRSHQODEHOSDUDOOHOJURXSVWXG\SHUIRUPHG
LQ VXEMHFWV LQ )UHQFK SULPDU\ DQG UHVSLUDWRU\ FDUH VSHFLDOLVW ZKR KDYH D GLDJQRVLV RI
DVWKPD DQG D UHJXODU WUHDWPHQW IRU SHUVLVWHQW DVWKPD 6XEMHFWV ZLWK XQVDWLVIDFWRULO\
FRQWUROOHG DVWKPD GHILQHG DV DQ $&7   DQG LQWHQGHG WR EH WUHDWHG E\ XVXDO
,&6/$%$ PDLQWHQDQFH WKHUDS\ WR VHHN D EHWWHU FRQWURO RI WKHLU DVWKPD ZLOO EH
UDQGRPLVHGWRUHFHLYHHLWKHU))9,))9,PFJPFJRU))9,PFJPFJRQFH
GDLO\RUDQRWKHUXVXDO,&6/$%$FRPELQDWLRQWKHUDS\LQLQKDODWLRQSRZGHUWZLFHGDLO\
)36RU%8')GHFLGHGE\WKHSK\VLFLDQ7KHVHPHGLFDWLRQVDUHUHFRUGHGLQWKHH&5)
3K\VLFLDQVZLOOEHDOORZHGGXULQJWKHWUHDWPHQWSHULRGWRDGDSWSUHVFULSWLRQWRGLIIHUHQW
GRVHVLIQHFHVVDU\DVZHOODVWRDGDSWGRVHVRIDQ\FRPSDUDWLYHWUHDWPHQWDFFRUGLQJWR
SURGXFWV ODEHO $ WDEOH 7DEOH  6HFWLRQ  RI WKH LQGLFDWLYH GRVDJH HTXLYDOHQFH
EHWZHHQ,&6DQGWKHRWKHUFRPELQDWLRQWKHUDSLHVZLOOEHSURYLGHGWRWKHSK\VLFLDQV

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
19
)RU6WXG\6FKHPDWLFVHH$SSHQGL[
,QYHVWLJDWRUV
*HQHUDO3UDFWLWLRQHUVDQGSXOPRQRORJLVWV EDVHGLQ)UDQFHDOODFFUHGLWHGIRUFOLQLFDOWULDOV
E\D&33³&RPLWpGH3URWHFWLRQGHV3HUVRQQHV´ZLOOEHDSSURDFKHGWRSDUWLFLSDWHLQWKH
VWXG\DSSUR[LPDWHO\*HQHUDO3UDFWLWLRQHUVSXOPRQRORJLVWV
6FUHHQLQJUDQGRPLVDWLRQDQGIROORZXS
$WWKH6FUHHQLQJ9LVLWHOLJLEOHVXEMHFWVZLOOEHFRQVHQWHGWRSDUWLFLSDWHWRWKHWULDODQG
SUHVFULEHGWKHQHFHVVDU\H[DPLQDWLRQV7KHVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWR
WKH$&7$VFUHHQLQJORJZLOOEHSHUIRUPHGDWWKLVYLVLW
$WDIXUWKHUYLVLWLH9'D\RFFXUULQJZLWKLQZHHNDIWHUWKHVFUHHQLQJYLVLW9
VXEMHFWVZKRPHHWDOORIWKH,QFOXVLRQ&ULWHULDQRQHRIWKH([FOXVLRQ&ULWHULDDQGZKR
DFFHSWWRJLYHWKHLUFRQVHQWZLOOEHUDQGRPLVHGLQWKHVWXG\5DQGRPLVDWLRQDWWKLVYLVLW
ZLOOEHRQDEDVLVWRWKH))9,IL[HGGRVHFRPELQDWLRQGHOLYHUHGE\(OOLSWD RUWRWKH
LQLWLDWLRQRI DQ\ XVXDO ,&6/$%$ '3, IRUDVWKPDPDLQWHQDQFHWKHUDS\FKRVHQE\WKH
SK\VLFLDQ 9LVLW  DQG 9LVLW  FDQ EH FRPELQHG LI WKH VXEMHFW GLG QRW WDNH KLV XVXDO
DVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH,I9LVLWDQG9LVLWDUHFRPELQHGWKHQWKLV
YLVLWZLOOEH'D\
$W9LVLW5DQGRPLVDWLRQ YLVLW'D\EDVHOLQHSUHGRVH)(9ZLOOEHDVVHVVHG E\WKH
,QYHVWLJDWRUXVLQJDVSLURPHWHUSURYLGHGE\*6. $WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOG
EHSHUIRUPHGZLWKUHJLVWUDWLRQRIWKHEHVWYDOXH2QWKHPRUQLQJRI9LVLWVXEMHFWVZLOO
QRWWDNHWKHLUXVXDODVWKPDPHGLFDWLRQ5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHG
KRXUVEHIRUHEDVHOLQHVSLURPHWU\
,QDGGLWLRQDW9LVLWVXEMHFWVZLOOEHDVNHGWRUHDGWKHZULWWHQ(OOLSWD SDFNDJHLQVHUWLI
UDQGRPLVHG LQWR WKH ))9, DUP RU 'LVNXV RU 7XUEXKDOHU LI UDQGRPLVHG LQ WKH XVXDO
,&6/$%$WKHUDS\DUPDQGZLOOEHLQVWUXFWHGE\WKHLQYHVWLJDWRURQWKHSURSHUXVHRI
LQKDOHUV 7KHQ WKH VXEMHFW ZLOO VHOIDGPLQLVWHU WKHLU ILUVW GRVH RI VWXG\ GUXJ XQGHU
VXSHUYLVLRQRI WKHLQYHVWLJDWRU $Q\PLVWDNHV7\SH$ HUURUV OLNHO\WR EHFULWLFDO DQG
RYHUDOOHUURUV ZLOO EH UHJLVWHUHGE\ WKHWUDLQHG +&3 $IWHU FRPSOHWLQJ WKHSURFHGXUH
VXEMHFWV ZLOO EH LQVWUXFWHG LQ WKH FRUUHFW XVH RI WKH GHYLFH E\ WKH WUDLQHG SK\VLFLDQ LI
QHHGHG7KHUHDIWHU HDFKVXEMHFWUDQGRPLVHGLQWRWKH))9,DUPZLOOEHLQVWUXFWHGWRVHOI
DGPLQLVWHURQHLQKDODWLRQZLWK(OOLSWD LQKDOHUHDFKGD\DWWKHVDPH WLPHRIWKHGD\DWD
WLPHWKDWLVFRQYHQLHQWIRUWKHVXEMHFW 6XEMHFWUDQGRPLVHGLQWRXVXDO,&6/$%$WKHUDS\
DUP ZLOO EH LQVWUXFWHG WR VHOIDGPLQLVWHU WKH LQKDODWLRQ ZLWK 'LVNXV RU 7XUEXKDOHU
LQKDOHUWZLFHDGD\
6XEMHFWV ZLOO EH UHFRPPHQGHG WR XVH 6DOEXWDPRO DV QHHGHG WKURXJKRXW WKH VWXG\ IRU
UHOLHIRIWKHLUDVWKPDV\PSWRPV$W9LVLWUDQGRPLVDWLRQ'D\VXEMHFWZLOOEHDVNHG
WRSURYLGHUHVSRQVHVWRWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
$W :HHN  9LVLW  DQG DW :HHN  9LVLW  VXEMHFWV ZLOO EH WHOHSKRQHG E\ WKH
,QYHVWLJDWRU WR HQTXLUH DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ DGYHUVH HYHQWV
RQO\WKHVHULRXVDGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV ZLOOEHUHFRUGHGLQ

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
20
H&5) 7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDV WRZKHWKHULWLVUHODWHGRUQRWWRVWXG\
WUHDWPHQW $W WKHVH WHOHSKRQH FDOOV VXEMHFWV ZLOO DOVR EH DVNHG WR FRPSOHWH WKH $&7
TXHVWLRQQDLUHSDSHUYHUVLRQDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
9LVLW6XEMHFWVZLOOEHDVNHGWRZLWKKROGIURPWDNLQJVWXG\PHGLFDWLRQRQWKHGD\RI
9LVLW$WWKLVYLVLW VXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&70$56$
DQG 3$6$3 TXHVWLRQQDLUHV DQG WKH LQKDOHU XVH ZLOO EH DVVHVVHG E\ UHFRUGLQJ 7\SH $
HUURUVDQGRYHUDOOHUURUVIROORZLQJWKHQH[WSURFHGXUHVHOIDGPLQLVWUDWLRQRIRQHGRVHRI
VWXG\GUXJHUURUVDVVHVVPHQWE\WKHLQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHU
LQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ3UHGRVHWURXJK)(9ZLOOEHDVVHVVHGDWWKLVYLVLWE\
WKH,QYHVWLJDWRUXVLQJWKH VSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPRO
ZLOOEHVWRSSHGKRXUVEHIRUHWKHVSLURPHWU\$WOHDVWWKUHHYDOLGDVVHVVPHQWVVKRXOGEH
SHUIRUPHG ZLWK UHJLVWUDWLRQ RI WKH EHVW YDOXH $W WKLV YLVLW VXEMHFWV ZLOO DOVR EH
LQWHUYLHZHGE\WKH,QYHVWLJDWRUDERXWZKHWKHUWKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVH
HYHQWV RQO\ WKH VHULRXV DGYHUVH HYHQWV RU QRQ±VHULRXV DGYHUVH GUXJ UHDFWLRQV ZLOO EH
UHFRUGHGLQH&5)7KH,QYHVWLJDWRUPDNHVWKHMXGJPHQWDVWRZKHWKHULWLVUHODWHGRUQRW
WRVWXG\WUHDWPHQW)HPDOHVXEMHFWVRIFKLOGEHDULQJSRWHQWLDOZLOODOVREHUHPLQGHGDERXW
WKHUHTXLUHPHQWIRUFRQWUDFHSWLRQWKURXJKRXWWKHLUVWXG\SDUWLFLSDWLRQ
7KH ILQDO 9LVLW  ZLOO RFFXU DW :HHN  7KH $&7 $4/46 (4' DQG 0$56$
TXHVWLRQQDLUHV ZLOO EH FRQGXFWHG DW WKLV YLVLW DQG WKH LQKDOHU XVH ZLOO EH DVVHVVHG E\
UHFRUGLQJ 7\SH $ HUURUV DQG RYHUDOO HUURUV IROORZLQJ WKH QH[W SURFHGXUH VHOI
DGPLQLVWUDWLRQ RI RQH GRVH RI VWXG\ GUXJ E\ VXEMHFW HUURUV DVVHVVPHQW E\ WKH
LQYHVWLJDWRUGHPRQVWUDWLRQRIFRUUHFWXVHRILQKDOHULQFDVHRIPXOWLSOHHUURUVGHWHFWLRQ
6XEMHFWV ZLOO EH LQWHUYLHZHG DERXW ZKHWKHU WKH VXEMHFW KDV H[SHULHQFHG DQ\ VHULRXV
DGYHUVHHYHQWVRUQRQ±VHULRXVDGYHUVHGUXJUHDFWLRQV 7KH,QYHVWLJDWRUZLOOEHDVNHGWR
PDNHHYHU\HIIRUWWRVFKHGXOH9LVLWDWWKHVDPHWLPHRIWKHGD\DV 9LVLW
$OWKRXJKDWOHDVWIRUPDOVFKHGXOHGYLVLWVDQGSKRQHFDOOVDUHSODQQHGIRUWKLVVWXG\
VXEMHFWVVKRXOGFRQWLQXHWRYLVLWWKHLUSK\VLFLDQIRUDQ\URXWLQHQDWXUDOLVWLFYLVLWVDVSHU
QRUPDO FOLQLFDO SUDFWLFH DV SHU WKH 7LPH DQG (YHQWV 7DEOH 6HFWLRQ  $Q (DUO\
:LWKGUDZDO9LVLWKDV WREHFRQVLGHUHGLQFDVHRIHDUO\ZLWKGUDZDORIWKHVXEMHFWIURPWKH
VWXG\DVSHUWKH7LPHDQG(YHQWV7DEOH6HFWLRQ
3URWRFROZDLYHUVRUH[HPSWLRQVDUHQRWDOORZHGZLWKWKHH[FHSWLRQRILPPHGLDWHVDIHW\
FRQFHUQV 7KHUHIRUH DGKHUHQFH WR WKH VWXG\ GHVLJQ UHTXLUHPHQWV LQFOXGLQJ WKRVH
VSHFLILHGLQWKH7LPHDQG(YHQWV7DEOHDUHHVVHQWLDODQGUHTXLUHGIRUVWXG\FRQGXFW
6XSSOHPHQWDU\VWXG\FRQGXFWLQIRUPDWLRQQRWPDQGDWHGWREHSUHVHQWLQWKLVSURWRFROLV
SURYLGHGLQWKHDFFRPSDQ\LQJ6WXG\3URFHGXUHV0DQXDO6307KH630ZLOOSURYLGH
WKHVLWH SHUVRQQHO ZLWK DGPLQLVWUDWLYHDQGGHWDLOHGWHFKQLFDOLQIRUPDWLRQWKDWGRHV QRW
LPSDFWVXEMHFWVDIHW\

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
21
2XWFRPHGHVFULSWLRQ
2QHRIWKHPDLQFKDOOHQJHVRIWKLVVWXG\SHUIRUPHGLQVRFDOOHGµFORVHWRUHDOOLIHVHWWLQJ¶
LV WR REWDLQ GDWD RQ VXEMHFWV ZLWK PLQLPDO LQWHUIHUHQFH ZLWK WKH DFWXDO SUDFWLFH RI
PHGLFLQH7KXVGXULQJWKHPRQWKV WUHDWPHQWSHULRGRIWKHVWXG\DOOLQWHUYHQWLRQVZLOO
EHUHFRUGHGDVSHUQRUPDO7KH\ZLOOEHFDSWXUHGE\VHYHUDOPHDQV
 3K\VLFLDQVSDUWLFLSDWLQJ LQWKHVWXG\ ZLOOEHDVNHG WRILOOLQ DQHOHFWURQLF&5)
H&5) IRFXVHG RQ FOLQLFDO GDWD DW VFUHHQLQJ YLVLW 9LVLW  DW UDQGRPLVDWLRQ
9LVLWDW:HHN 9LVLWDWWKHHQGRIWKHVWXG\DW:HHN 9LVLWDQGDW
WZRSKRQHFDOOVDW:HHN 9LVLW DQGDW:HHN 9LVLW
 $W:HHN DQGDW :HHNVXEMHFWVZLOOEHWHOHSKRQHGWRHQTXLUHDERXWZKHWKHU
WKHVXEMHFWKDVH[SHULHQFHGDQ\DGYHUVHHYHQWVDQGWKHQWKHLQYHVWLJDWRUFDOOLQJ
WKHSDWLHQWPXVWGHWHUPLQHZKHWKHUWKHHYHQWLVUHODWHGWRVWXG\PHGLFDWLRQHLWKHU
DUPDQGZKHWKHUWKHHYHQWLVVHULRXV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVR
EHDVNHGE\WKH ,QYHVWLJDWRUWRFRPSOHWH WKH$&7TXHVWLRQQDLUHDQGWRVHQGLW
EDFNWRWKH,QYHVWLJDWRU
 :KHQ QHFHVVDU\ LQIRUPDWLRQ ZLOO EH REWDLQHG IURP RWKHU PHGLFDO VRXUFHV
QDWXUDOLVWLFYLVLWV
7KHYDULDEOHVRILQWHUHVWZLOOEHGRFXPHQWHGE\DFRPELQDWLRQRILQIRUPDWLRQFROOHFWHG
IURPDOOWKHVHVRXUFHV
&ROOHFWHGGDWD
(OLJLEOHVXEMHFWVZLOOFRPSOHWHWKH$&7$4/46(4'DQG0$56$TXHVWLRQQDLUHV
DW 5DQGRPLVDWLRQ 9LVLW 9LVLW  'D\  DQG DW 9LVLW  :HHN  RU DW WKH (DUO\
:LWKGUDZDOYLVLW$&7TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRE\WKHVXEMHFWDW6FUHHQLQJ
YLVLW9LVLW:HHNSKRQHFDOORU9LVLWDW:HHN9LVLWDQG:HHNSKRQH
FDOO RU9LVLW0$56$TXHVWLRQQDLUHZLOOEHFRPSOHWHGDOVRDW:HHN9LVLW
,QKDOHU XVH DVVHVVPHQW ZLOO EH SHUIRUPHG DW 5DQGRPLVDWLRQ 9LVLW 9LVLW  'D\  DW
:HHN9LVLWDQGDW:HHN9LVLW(DUO\:LWKGUDZDOYLVLWE\UHFRUGLQJWKH
7\SH$ HUURUVDQGWKHRYHUDOOHUURUV3DWLHQW¶V VDWLVIDFWLRQDQGSUHIHUHQFH3$6$34
ZLOOEHHYDOXDWHGDW:HHN9LVLW
%DVHOLQHVSLURPHWU\ZLOOEHSHUIRUPHGDW5DQGRPLVDWLRQ9LVLW9LVLW 'D\DQGDW
:HHN9LVLWE\WKH,QYHVWLJDWRUXVLQJWKH VSLURPHWHUSURYLGHGE\*6.LQRUGHUWR
DVVHVVSUHGRVHWURXJK)(9 DW:HHN9LVLW
)RU WKH 6WXG\ 6FKHPDWLF VHH $SSHQGL[  DQG 6HFWLRQ  IRU WKH SURSRVHG WLPH DQG
HYHQWVWDEOH

7UHDWPHQWDUPVDQGGXUDWLRQ
5DQGRPLVDWLRQZLOOEHRQDEDVLV ZLWK WZRWUHDWPHQWDUPVRQH))9,DUP
))9, PFJ PFJRU))9, PFJ PFJRQFHGDLO\DQGRQHDUP,&6/$%$
FRPELQDWLRQWKHUDS\LQLQKDODWLRQSRZGHUWZLFHGDLO\)36 PFJ PFJRU

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
22
PFJPFJRU%8' )  PFJPFJRU PFJPFJDVGHFLGHGE\WKHSK\VLFLDQ
7KHWRWDOGXUDWLRQRIVXEMHFWSDUWLFLSDWLRQZLOOEHDSSUR[LPDWHO\PRQWKVZHHNV$V
PXFKDVSRVVLEOHHQUROPHQWRIVXEMHFWVVKRXOGEHSHUIRUPHGDWDFRQVWDQWDFFUXDOUDWH
WKURXJKRXWDIXOO\HDULQRUGHUWRPLQLPL]HDVHDVRQDOLW\ELDV

7\SHDQG1XPEHURI6XEMHFWV
6XEMHFWV ZLWK GRFXPHQWHG SK\VLFLDQ¶V GLDJQRVLV RI DVWKPD   \HDU XQVDWLVIDFWRULO\
FRQWUROOHG DVWKPD $&7   WUHDWHG E\ ,&6 DORQH DQG LQWHQGHG WR EH WUHDWHG E\
,&6/$%$ PDLQWHQDQFH WKHUDS\ $ VXEMHFW ZLOO EH HOLJLEOH IRU LQFOXVLRQ LQ WKLV VWXG\
RQO\LIHLWKHUDIILOLDWHGWRRUDEHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
,WLVHVWLPDWHGWKDWDSSUR[LPDWHO\ VWXG\FHQWHUVLQ)UDQFHZLOOEHUHTXLUHGWRKDYHD
WRWDOQXPEHURIUDQGRPLVHGVXEMHFWV VRWKDWDWOHDVWVXEMHFWVZLOOEHHYDOXDEOH
$VVXPLQJDRIVFUHHQIDLOXUHVXEMHFWVZLOOKDYHWREHVFUHHQHGLQWKHVWXG\ZLWK
VXEMHFWVFHQWHU
6XEMHFWVZLWKGUDZQIURPWKHVWXG\ZLOOQRWEHUHSODFHG

'HVLJQ-XVWLILFDWLRQ
$Q RSHQ ODEHO GHVLJQ LV DSSURSULDWH IRU VXFK D VWXG\ EHFDXVH LW LV D FRPSDULVRQ RI
EHQHILWVDQGULVNVRI))9,YHUVXVXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\LQFORVH
WRUHDOOLIHVHWWLQJ
3UHYLRXV VWXGLHV KDYH GHPRQVWUDWHG WKDW LPSURYHPHQWV LQ $&7 VFRUH FDQ EH VHHQ LQ
SHULRGVRIPRQWKVPDNLQJWKLVVXLWDEOHWLPHIUDPHWRDVVHVV$&7FKDQJHV
7KHWUHDWPHQWGXUDWLRQRIPRQWKVZHHNVLQWKLVVWXG\LVFRQVLGHUHGVXIILFLHQWWR
GHPRQVWUDWHHIILFDF\LQWKHSURSRVHGVWXG\SRSXODWLRQ
7KH SULPDU\ HQGSRLQW LV GHILQHG DV WKH FKDQJH IURP EDVHOLQH LQ WKH $&7 WRWDO VFRUH
DVVHVVHGDW:HHN9LVLW7KHDLPZLOOEHWRSURYHQRQLQIHULRULW\RI))9,WRDQ\
RWKHU ,&6/$%$ FRPSDUDWRU 7KH K\SRWKHVLV RI QRQLQIHULRULW\ ZLOO EH ILUVW WHVWHG DW
:HHN  ,I DQG RQO\ LI QRQLQIHULRULW\ LV VLJQLILFDQWO\ DFKLHYHG DW :HHN  QRQ
LQIHULRULW\ZLOOWKHQEHWHVWHGDW:HHN,IDQGRQO\LIQRQLQIHULRULW\LVDFKLHYHGDWD
YLVLWWKHQVXSHULRULW\RI))9,WRDQ\RWKHUFRPSDUDWRUZLOOEHWHVWHGDWWKLVYLVLW:HHN
RU:HHN

'RVH-XVWLILFDWLRQ
7ZR VWUHQJWKV RI ))9, KDYH EHHQ DSSURYHG  PFJ PFJ GHOLYHUHG GRVH RI 
PFJ PFJIRUPRGHUDWHSHUVLVWHQWDVWKPD DQG PFJ PFJ GHOLYHUHGGRVHRI
PFJ PFJ IRU VHYHUH SHUVLVWHQW DVWKPD 7KH GRVH RI  PFJ  PFJ ZLOO EH
SUHIHUHQWLDOO\SURJUHVVHGLQWKLVVWXG\DVWKLVGRVHVWUHQJWKLVOLNHO\WRPHHWWKHQHHGVRI
PRVWVXEMHFWV+RZHYHUSK\VLFLDQVZLOOEHDOORZHGWRFKDQJHWKHSUHVFULSWLRQWRKLJKHU
GRVHDFFRUGLQJWRVXEMHFW¶VUHVSRQVHZLWKRXWH[FHHGLQJWKHPD[LPXPDOORZHGGRVH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
23

%HQHILW5LVN$VVHVVPHQW
6XPPDULHV RIILQGLQJVIURPERWKFOLQLFDODQGQRQFOLQLFDOVWXGLHVFRQGXFWHGZLWK))9,
FDQEHIRXQGLQWKH,QYHVWLJDWRU¶V%URFKXUH,%RU6XPPDU\RI3URGXFW&KDUDFWHULVWLFV
63&7KHIROORZLQJVHFWLRQRXWOLQHVWKHULVNDVVHVVPHQWDQGPLWLJDWLRQVWUDWHJ\IRUWKLV
SURWRFRO

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
24

5LVN$VVHVVPHQW
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
6HULRXV&DUGLRYDVFXODU(YHQWV
7KLVLVDSRWHQWLDOFODVVHIIHFWRI/$%$V,Q
FOLQLFDOVWXGLHVSHUFHQWDJHVRIVXEMHFWVZLWK
IDWDOHYHQWVWKDWZHUHFDUGLRYDVFXODULQ
QDWXUHZHUHVLPLODUDFURVVDOOWUHDWPHQW
JURXSVWR
6XEMHFWVZLWKKLVWRULFDORUFXUUHQWHYLGHQFH
RIXQFRQWUROOHGRUFOLQLFDOO\VLJQLILFDQW
GLVHDVHDUHH[FOXGHGIURPWKHVWXG\
&DUGLRYDVFXODUPHGLFDOKLVWRU\&9ULVN
IDFWRUVDQGH[DFHUEDWLRQKLVWRU\ZLOOEH
DVVHVVHGDVGHVFULEHGLQWKHWLPHDQGHYHQWV
WDEOH
$VWKPDUHODWHGLQWXEDWLRQVDQGGHDWKV
7KLVLVDSRWHQWLDOFODVVHIIHFWRI/$%$V,W
ZDVQRWREVHUYHGLQSUHFOLQLFDOVWXGLHVZLWK
))9,'XULQJWKH))9,VWXGLHVIRUWKH
DVWKPDFRPSRVLWHHQGSRLQWDVWKPD
H[DFHUEDWLRQVOHDGLQJWRKRVSLWDOL]DWLRQ
LQWXEDWLRQDQGRUGHDWKWKHUHZDVQR
VLJQLILFDQWGLIIHUHQFH
EHWZHHQWKH))9,JURXSDQGWKH,&6JURXS
RU
QRQ/$%$JURXSGHPRQVWUDWLQJQR
LQFUHDVHGULVNZKHQDGGLQJD/$%$WRDQ
,&6
6XEMHFWVZLWKDKLVWRU\ RIOLIHWKUHDWHQLQJ
DVWKPDDUHH[FOXGHGIURPWKLVVWXG\
6XEMHFWVDUHH[FOXGHGIURPWKLVVWXG\ LIWKH\
KDYHDVHYHUHDQGXQVWDEOHDVWKPDZLWK
$&7 VFRUHKLVWRU\RIUHSHDWHGVHYHUH
H[DFHUEDWLRQV\HDUDQGRUH[DFHUEDWLRQ
LQWKHSUHYLRXVZHHNV
6XEMHFWVDUHH[FOXGHGIURPWKLVVWXG\LIWKH\
DUHXVLQJ/$%$ZLWKRXWDQ,&6DVDVWKPD
PDLQWHQDQFHWKHUDS\



2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
25
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
+\SHUVHQVLWLYLW\
7KHUHSRUWHGK\SHUVHQVLWLYLW\HYHQWVLQ
FOLQLFDOWULDOVZHUHQRWJHQHUDOO\VHULRXV
GLGQRWOHDGWRGLVFRQWLQXDWLRQLQWKH
VWXGLHVDQGZHUHXVXDOO\FRQIRXQGHGE\
HLWKHUWKHVXEMHFW¶VPHGLFDOFRQGLWLRQVXFK
DV&23'RURWKHUIDFWRUVDWWKHWLPHRIWKH
HYHQW
,QVSRQWDQHRXVGDWDV\PSWRPVRI
K\SHUVHQVLWLYLW\UDQJHGIURPPLOGUDVKDQG
SUXULWLVWRVHYHUHJHQHUDOLVHGUDVKDQG
HU\WKHPDDQGVHYHUHFDVHVLQYROYLQJ
DQJLRGHPDRIWKHIDFHODU\Q[DQGSKDU\Q[
7KHVHHYHQWVZHUHUDUH
6XEMHFWV ZLWKDKLVWRU\ RIDGYHUVHUHDFWLRQ
LQFOXGLQJ
LPPHGLDWH
RU
GHOD\HG
K\SHUVHQVLWLYLW\ WR DQ\ LQWUDQDVDO LQKDOHG
RU V\VWHPLF FRUWLFRVWHURLG DQG /$%$
WKHUDS\DQGWRFRPSRQHQWVRIWKHLQKDODWLRQ
SRZGHUHJODFWRVHPDJQHVLXPVWHDUDWH
,QDGGLWLRQVXEMHFWVZLWKDKLVWRU\RIVHYHUH
PLONSURWHLQDOOHUJ\WKDWLQWKHRSLQLRQRI
WKH
,QYHVWLJDWRU
FRQWUDLQGLFDWHV
WKH
VXEMHFW¶VSDUWLFLSDWLRQZLOODOVREHH[FOXGHG
6\VWHPLFHIIHFWVRIFRUWLFRVWHURLGVDGUHQDO
VXSSUHVVLRQH\HGLVRUGHUVGHFUHDVHGERQH
GHQVLW\DQGDVVRFLDWHGIUDFWXUHV
$GUHQDOVXSSUHVVLRQLVDNQRZQFODVVHIIHFW
RIFRUWLFRVWHURLGV3UHFOLQLFDOVWXGLHV
VKRZHGWKDW))HIIHFWVDUHFRPSDUDEOHZLWK
RWKHUFRUWLFRVWHURLGV1RVWXGLHVKDYH
VKRZQDFOLQLFDOO\UHOHYDQWHIIHFWRI))9,
RQWKHK\SRWKDODPLFSLWXLWDU\D[LV+3$
7KLVLQFOXGHVDIRUPDO+3$VWXG\
+=$XVLQJKRXUVHUXPFRUWLVRO
PHDVXUHPHQWVDQGPXOWLSOHVWXGLHVZLWK
&23'DQGDVWKPDVXEMHFWVZKLFK
PRQLWRUHGXULQDU\FRUWLVRO'XULQJFOLQLFDO
7KHPLWLJDWLRQLQWKLVVWXG\IRUDOOV\VWHPLF
HIIHFWV RI FRUWLFRVWHURLGV LV WKDW FKURQLF
XVHUV
RI
V\VWHPLF
FRUWLFRVWHURLGV
DUH
H[FOXGHGIURPWKLVVWXG\DVXEMHFWZKRLQ
WKHRSLQLRQRIWKH,QYHVWLJDWRULVFRQVLGHUHG
WR
EH
D
FKURQLF
XVHU
RI
V\VWHPLF
FRUWLFRVWHURLGV IRU UHVSLUDWRU\ RU RWKHU
LQGLFDWLRQV LI XQVXUH GLVFXVV ZLWK WKH
PHGLFDOPRQLWRUSULRUWRVFUHHQLQJ



2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
26
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
GHYHORSPHQWQRHYHQWVRI$GUHQDO
6XSSUHVVLRQZHUHUHSRUWHG
(\HGLVRUGHUVDUHDNQRZQFODVVHIIHFWRI
FRUWLFRVWHURLGV3UHFOLQLFDOVWXGLHVVKRZHG
))DWKLJKGRVHFRPSDUDEOHWRRWKHUKLJK
GRVHFRUWLFRVWHURLGV,QVWXG\+=$
))9,))DQG)3LQVXEMHFWVZLWKDVWKPD
IRUPDORSKWKDOPLFDVVHVVPHQWVZHUH
FRQGXFWHGLQFOXGLQJ/2&6,,,HYDOXDWLRQV
IRURFXODURSDFLWLHVWKURXJKRXWWKHVWXG\
7KLVVWXG\VKRZHGQRDSSDUHQWHIIHFWVRQ
OHQVRSDFLILFDWLRQFRPSDUHGWREDVHOLQH
'XULQJVWXGLHVLQERWKVXEMHFWVZLWKDVWKPD
DQG&23'QRDVVRFLDWHGDIIHFWRQRFXODU
GLVRUGHUVZDVREVHUYHG
'HFUHDVHGERQHGHQVLW\LVDGRZQFODVV
HIIHFWRIFRUWLFRVWHURLGV3UHFOLQLFDOGDWD
VKRZHGWKDWKLJKGRVHFRUWLFRVWHURLGHIIHFWV
RI))ZHUHFRPSDUDEOHWRRWKHU
FRQUWLFRVWHURLGV3DWLHQWVZLWK$VWKPD,QDQ
LQWHJUDWHGDQDO\VLVRIVWXGLHVLQDVWKPD
SDWLHQWVWKHLQFLGHQFHRIIUDFWXUHV
ZLWK))9,ZDV DQGXVXDOO\
DVVRFLDWHGZLWKWUDXPD



2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
27
Investigational Product (IP) [FF/VI] 
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Procedures
6SLURPHWU\SURFHGXUHV
6KRUWQHVVRIEUHDWKFRXJKLQJOLJKW
KHDGHGQHVVRUIDLQWLQJDQGRUFKHVW
WLJKWQHVV
,IDQ\RIWKHVHV\PSWRPVVKRXOGKDSSHQWR
WKHVXEMHFWVSLURPHWU\ ZLOOEHVWRSSHGDQG
KHVKHZLOOUHFHLYHPHGLFDOWUHDWPHQW
Other 
6XPPDULHVRIILQGLQJVIURPERWKFOLQLFDODQGQRQFOLQLFDOVWXGLHVFRQGXFWHGZLWKFRPSDUDWRUV6HUHWLGH'LVNXVDQG6\PELFRUW
7XUEXKDOHUFDQEHIRXQGLQWKH6XPPDU\RI3URGXFW&KDUDFWHULVWLFV63&



2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
28

%HQHILW$VVHVVPHQW
&RPELQHGWUHDWPHQWZLWK,&6DQG/$%$KDVEHHQVKRZQWREHPRUHHIIHFWLYHWKDQWKH
LQGLYLGXDOFRPSRQHQWVLQDVWKPDOHDGLQJWR WKHGHYHORSPHQWRIIL[HGGRVHFRPELQDWLRQ
LQKDOHUV 7KH XVH RI ,&6/$%$ FRPELQDWLRQV LV QRZ ZHOO HVWDEOLVKHG LQ LQWHUQDWLRQDO
WUHDWPHQW JXLGHOLQHV IRU PRGHUDWH WR VHYHUH SHUVLVWHQW DVWKPD SDWLHQWV IRU ZKRP
WUHDWPHQWZLWK,&6DORQHLVQRWVXIILFLHQW
%RWK
IOXWLFDVRQH SURSLRQDWHVDOPHWHURO DQG EXGHVRQLGHIRUPRWHURO IXPDUDWH DUH
FRPPHUFLDOO\ DYDLODEOH SURGXFWV IRU WKH WUHDWPHQW RI SHUVLVWHQW DVWKPD DQG KDYH
UHFRJQL]HGVDIHW\SURILOHV%RWKRIWKHVHSURGXFWVDUHDGPLQLVWHUHGWZLFHGDLO\

2YHUDOO %HQHILW5LVN&RQFOXVLRQ
7KHLQYHVWLJDWLRQDOSURGXFW,3))9,KDVDQDFFHSWDEOHVDIHW\SURILOHIRU FOLQLFDOXVH
DQGWKHUHDUHQRVLJQLILFDQWDVVRFLDWHGULVNV7KLVFRQFOXVLRQLVVXSSRUWHGWKHUHVXOWVRI
SUHYLRXVO\SHUIRUPHGFOLQLFDOVWXGLHVZLWKWKHSURGXFWVLQKHDOWK\ YROXQWHHUVDQGVXEMHFWV
ZLWK $VWKPD DQG &23' *OD[R6PLWK.OLQH 'RFXPHQW 1XPEHU 50
$GYHUVHHIIHFWVWKDWFRXOGEHDVVRFLDWHGZLWKWKHXVHRI))9,ZLOO EHFORVHO\PRQLWRUHG
$ VDIHW\ FULWHULRQ RXWOLQLQJ GHWDLOV IRU VXEMHFW ZLWKGUDZDO LV LQFOXGHG LQ WKH SURWRFRO
6HFWLRQ :LWKGUDZDO&ULWHULD$WKRURXJKVXPPDU\DQG HYDOXDWLRQRIWKHDYDLODEOH
SUHFOLQLFDO GDWD FDQ EH IRXQG LQ WKH ,% >*OD[R6PLWK.OLQH 'RFXPHQW 1XPEHU
50@ 5RXWLQH VDIHW\ DQDO\VLV RI WKLV VWXG\ ZLOO EH FRQGXFWHG E\ WKH
FRPSDQ\ 7DNLQJ LQWR DFFRXQW WKH PHDVXUHV WDNHQ WR PLQLPL]H ULVN WR VXEMHFWV
SDUWLFLSDWLQJ LQ WKLV VWXG\ WKH SRWHQWLDO ULVNV LGHQWLILHG LQ DVVRFLDWLRQ ZLWK ))9, DUH
MXVWLILHG E\ WKH DQWLFLSDWHG EHQHILWV WKDW PD\ EH DIIRUGHG WR SDWLHQWV ZLWK DVWKPD

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
29

6(/(&7,212)678'<3238/$7,21 $1'
:,7+'5$:$/&5,7(5,$
6SHFLILFLQIRUPDWLRQUHJDUGLQJZDUQLQJVSUHFDXWLRQVFRQWUDLQGLFDWLRQVDGYHUVHHYHQWV
DQG RWKHU SHUWLQHQW LQIRUPDWLRQ RQ WKH *6. LQYHVWLJDWLRQDO SURGXFW RU RWKHU VWXG\
WUHDWPHQWWKDWPD\LPSDFWVXEMHFWHOLJLELOLW\LVSURYLGHGLQWKH,%,%VXSSOHPHQWVRU
WKH63&DQGRWKHUSHUWLQHQWGRFXPHQWV

,QFOXVLRQ&ULWHULD
'HYLDWLRQVIURPLQFOXVLRQFULWHULDDUHQRWDOORZHGEHFDXVHWKH\FDQSRWHQWLDOO\MHRSDUGLVH
WKHVFLHQWLILFLQWHJULW\RIWKHVWXG\UHJXODWRU\DFFHSWDELOLW\RUVXEMHFWVDIHW\7KHUHIRUH
DGKHUHQFHWRWKHFULWHULDDVVSHFLILHGLQWKHSURWRFROLVHVVHQWLDO
6XEMHFWVHOLJLEOHIRUHQUROPHQWLQWKHVWXG\PXVWPHHWDOORIWKHIROORZLQJFULWHULD
 ,QIRUPHG FRQVHQW &DSDEOH RI JLYLQJ VLJQHG LQIRUPHG FRQVHQW DV GHVFULEHG LQ
6HFWLRQ ZKLFKLQFOXGHVFRPSOLDQFHZLWKWKHUHTXLUHPHQWVDQGUHVWULFWLRQVOLVWHG
LQWKHFRQVHQWIRUPDQGLQWKLVSURWRFRO
 *HQGHUDQG$JH0DOHRUIHPDOHVXEMHFWVDJHG∀DQG\HDUVRIDJHDW9LVLW
)HPDOHVXEMHFW LVHOLJLEOHWRSDUWLFLSDWHLIVKHLVQRWSUHJQDQWDVFRQILUPHGE\D
QHJDWLYHXULQHKXPDQFKRULRQLFJRQDGRWURSKLQK&*WHVWQRWODFWDWLQJDQGDWOHDVW
RQHRIWKHIROORZLQJFRQGLWLRQVDSSOLHV
D
1RQUHSURGXFWLYHSRWHQWLDOGHILQHGDV
!
3UHPHQRSDXVDOIHPDOHVZLWKRQHRIWKHIROORZLQJ
!
'RFXPHQWHGWXEDOOLJDWLRQ
!
'RFXPHQWHGK\VWHURVFRSLFWXEDORFFOXVLRQSURFHGXUHZLWKIROORZXS
FRQILUPDWLRQRIELODWHUDOWXEDORFFOXVLRQ
!
+\VWHUHFWRP\
!
'RFXPHQWHG%LODWHUDO2RSKRUHFWRP\
!
3RVWPHQRSDXVDOGHILQHGDVPRQWKVRIVSRQWDQHRXVDPHQRUUKHD>LQ
TXHVWLRQDEOHFDVHVDEORRGVDPSOHZLWKVLPXOWDQHRXVIROOLFOHVWLPXODWLQJ
KRUPRQH)6+DQGHVWUDGLROOHYHOVFRQVLVWHQWZLWKPHQRSDXVHUHIHUWR
ODERUDWRU\UHIHUHQFHUDQJHVIRUFRQILUPDWRU\OHYHOV@)HPDOHVRQKRUPRQH
UHSODFHPHQWWKHUDS\+57DQGZKRVHPHQRSDXVDOVWDWXVLVLQGRXEWZLOOEH
UHTXLUHGWRXVHRQHRIWKHKLJKO\HIIHFWLYHFRQWUDFHSWLRQPHWKRGVLIWKH\ZLVKWR
FRQWLQXHWKHLU+57GXULQJWKHVWXG\2WKHUZLVHWKH\PXVWGLVFRQWLQXH+57WR
DOORZFRQILUPDWLRQRISRVWPHQRSDXVDOVWDWXVSULRUWRVWXG\HQUROPHQW
E
5HSURGXFWLYHSRWHQWLDODQGDJUHHVWRIROORZRQHRIWKHRSWLRQVOLVWHGEHORZLQ
WKH*6.0RGLILHG/LVWRI+LJKO\(IIHFWLYH0HWKRGVIRU$YRLGLQJ3UHJQDQF\LQ
)HPDOHVRI5HSURGXFWLYH3RWHQWLDO)53UHTXLUHPHQWVIURPGD\VSULRUWRWKH
ILUVWGRVHRIVWXG\PHGLFDWLRQDQGXQWLO:HHN9LVLW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
30
*6.0RGLILHG/LVWRI+LJKO\(IIHFWLYH0HWKRGVIRU$YRLGLQJ3UHJQDQF\LQ)HPDOHV
RI5HSURGXFWLYH3RWHQWLDO)53
7KLVOLVWGRHVQRWDSSO\WR)53ZLWKVDPHVH[SDUWQHUVZKHQWKLVLVWKHLUSUHIHUUHGDQG
XVXDOOLIHVW\OHRUIRUVXEMHFWVZKRDUHDQGZLOOFRQWLQXHWREHDEVWLQHQWIURPSHQLOH
YDJLQDOLQWHUFRXUVHRQDORQJWHUPDQGSHUVLVWHQWEDVLV

&RQWUDFHSWLYHVXEGHUPDOLPSODQWWKDWPHHWVWKH623HIIHFWLYHQHVVFULWHULD
LQFOXGLQJDUDWHRIIDLOXUHSHU\HDUDVVWDWHGLQWKHSURGXFWODEHO

,QWUDXWHULQHGHYLFHRULQWUDXWHULQHV\VWHPWKDWPHHWVWKH623HIIHFWLYHQHVV
FULWHULDLQFOXGLQJDUDWHRIIDLOXUHSHU\HDUDVVWDWHGLQWKHSURGXFWODEHO
>+DWFKHUD@

2UDO&RQWUDFHSWLYHHLWKHUFRPELQHGRUSURJHVWRJHQDORQH>+DWFKHUD@

,QMHFWDEOHSURJHVWRJHQ>+DWFKHUD@

&RQWUDFHSWLYHYDJLQDOULQJ>+DWFKHUD@

3HUFXWDQHRXVFRQWUDFHSWLYHSDWFKHV>+DWFKHUD@

0DOHSDUWQHUVWHULOL]DWLRQZLWKGRFXPHQWDWLRQRID]RRVSHUPLDSULRUWRWKHIHPDOH
VXEMHFW
VHQWU\LQWRWKHVWXG\DQGWKLVPDOHLVWKHVROHSDUWQHUIRUWKDWVXEMHFW
>+DWFKHUD@

0DOHFRQGRPFRPELQHGZLWKDYDJLQDOVSHUPLFLGHIRDPJHOILOPFUHDPRU
VXSSRVLWRU\>+DWFKHUE@

7KHVH DOORZHG PHWKRGV RI FRQWUDFHSWLRQ DUH RQO\ HIIHFWLYH ZKHQ XVHG
FRQVLVWHQWO\ FRUUHFWO\ DQG LQ DFFRUGDQFH ZLWK WKH SURGXFW ODEHO  7KH
LQYHVWLJDWRULVUHVSRQVLEOHIRUHQVXULQJWKDWVXEMHFWVXQGHUVWDQGKRZWRSURSHUO\
XVHWKHVHPHWKRGVRIFRQWUDFHSWLRQ
 7\SHRIVXEMHFW
D
6XEMHFWV ZLWK GRFXPHQWHG SK\VLFLDQ¶V GLDJQRVLV RI DVWKPD   \HDU
XQVDWLVIDFWRULO\FRQWUROOHGDVWKPD $&7 DW9LVLWDQG9LVLWWUHDWHGE\
,&6DORQHDQGLQWHQGHGWREHWUHDWHGE\,&6/$%$PDLQWHQDQFHWKHUDS\
E
$VXEMHFWZLOOEHHOLJLEOHIRULQFOXVLRQLQWKLVVWXG\RQO\LIHLWKHUDIILOLDWHGWRRUD
EHQHILFLDU\RID6RFLDO6HFXULW\FDWHJRU\
 &XUUHQW$VWKPD7KHUDS\$OOVXEMHFWVPXVWEHSUHVFULEHGPDLQWHQDQFHWKHUDS\DQG
UHFHLYLQJ ,&6 DORQH ZLWKRXW /$%$ IRU DW OHDVW  ZHHNV SULRU WR 9LVLW 
5DQGRPLVDWLRQYLVLW
2WKHU EDFNJURXQG DVWKPD PHGLFDWLRQ VXFK DV DQWLOHXNRWULHQHV RU WKHRSK\OOLQH LV
SHUPLWWHG DV DQ DOWHUQDWLYH WR ,&6 DORQH LI LQLWLDWHG DW OHDVW  ZHHNV SULRU WR
VFUHHQLQJYLVLW 9LVLW
 6XEMHFW TXHVWLRQQDLUHV 6XEMHFWV PXVW EH DEOH WR FRPSOHWH WKH TXHVWLRQQDLUHV
WKHPVHOYHV

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
31

([FOXVLRQ&ULWHULD
'HYLDWLRQV IURP H[FOXVLRQ FULWHULD DUH QRW DOORZHG EHFDXVH WKH\ FDQ SRWHQWLDOO\
MHRSDUGLVHWKHVFLHQWLILFLQWHJULW\RIWKHVWXG\UHJXODWRU\DFFHSWDELOLW\RUVXEMHFWVDIHW\
7KHUHIRUHDGKHUHQFHWRWKHFULWHULDDVVSHFLILHGLQWKHSURWRFROLVHVVHQWLDO
6XEMHFWVPHHWLQJDQ\RIWKHIROORZLQJFULWHULDPXVWQRWEHHQUROOHGLQWKHVWXG\
 +LVWRU\RI/LIHWKUHDWHQLQJDVWKPD 'HILQHGIRUWKLVSURWRFRODVDQDVWKPDHSLVRGH
WKDWUHTXLUHGLQWXEDWLRQDQGRUZDVDVVRFLDWHGZLWKK\SHUFDSQHDUHVSLUDWRU\DUUHVWRU
K\SR[LFVHL]XUHVZLWKLQWKHODVWPRQWKV EHIRUH9LVLWDQG9LVLW
 6XEMHFWVKDYLQJDVHYHUHDQGXQVWDEOHDVWKPD ZLWK$&7 VFRUH DW9LVLWDQG
DW 9LVLW  KLVWRU\ RI UHSHDWHG VHYHUH H[DFHUEDWLRQV \HDU DQGRU D VHYHUH
H[DFHUEDWLRQLQWKHSUHYLRXVZHHNV EHIRUH9LVLWDQG9LVLW

&23'5HVSLUDWRU\'LVHDVH$VXEMHFWPXVWQRWKDYHFXUUHQWHYLGHQFHRUGLDJQRVLV
RIFKURQLFREVWUXFWLYH SXOPRQDU\GLVHDVH DW9LVLW

&XUUHQWRUIRUPHUFLJDUHWWHVPRNHUVZLWKDKLVWRU\RIFLJDUHWWHVPRNLQJRI
SDFN\HDUVDWVFUHHQLQJ9LVLW>QXPEHURISDFN\HDUV QXPEHURIFLJDUHWWHVSHU
GD\[QXPEHURI\HDUVVPRNHGHJFLJDUHWWHVSHUGD\IRU\HDUVRU
FLJDUHWWHVSHUGD\IRU\HDUV@
 2WKHU GLVHDVHVDEQRUPDOLWLHV 6XEMHFWV ZLWK KLVWRULFDO RU FXUUHQW HYLGHQFH RI
XQFRQWUROOHGRUFOLQLFDOO\VLJQLILFDQWGLVHDVH DW9LVLWDQGDW9LVLW6LJQLILFDQWLV
GHILQHGDVDQ\GLVHDVHWKDWLQWKHRSLQLRQRIWKH,QYHVWLJDWRUZRXOGSXWWKHVDIHW\RI
WKHVXEMHFWDWULVNWKURXJKSDUWLFLSDWLRQRUZKLFKZRXOGDIIHFWWKHHIILFDF\RUVDIHW\
DQDO\VLVLIWKHGLVHDVHFRQGLWLRQH[DFHUEDWHGGXULQJWKHVWXG\
 6XEMHFWV ZLWK D KLVWRU\ RI DGYHUVH UHDFWLRQ LQFOXGLQJ LPPHGLDWH RU GHOD\HG
K\SHUVHQVLWLYLW\ WR DQ\ LQWUDQDVDO LQKDOHG RU V\VWHPLF FRUWLFRVWHURLG DQG /$%$
WKHUDS\ DQG WR FRPSRQHQWV RI WKH LQKDODWLRQ SRZGHU HJ ODFWRVH PDJQHVLXP
VWHDUDWH DW9LVLWDQGDW9LVLW,QDGGLWLRQVXEMHFWVZLWKDKLVWRU\RIVHYHUHPLON
SURWHLQDOOHUJ\WKDWLQWKHRSLQLRQRIWKH,QYHVWLJDWRUFRQWUDLQGLFDWHVWKHVXEMHFW¶V
SDUWLFLSDWLRQZLOODOVREHH[FOXGHG
 ,QYHVWLJDWLRQDO0HGLFDWLRQV$VXEMHFWPXVWQRWKDYHXVHGDQ\LQYHVWLJDWLRQDOGUXJ
ZLWKLQ  GD\V SULRU WR 9LVLW  RU ZLWKLQ ILYH KDOIOLYHV Wò RI WKH SULRU
LQYHVWLJDWLRQDO VWXG\ ZKLFKHYHU LV ORQJHU RI WKH WZR LI XQVXUH GLVFXVV ZLWK WKH
PHGLFDOPRQLWRUSULRUWRVFUHHQLQJ
 &KURQLF XVHU RI V\VWHPLF FRUWLFRVWHURLGV $ VXEMHFW ZKR LQ WKH RSLQLRQ RI WKH
,QYHVWLJDWRU LV FRQVLGHUHG WR EH D FKURQLF XVHU RI V\VWHPLF FRUWLFRVWHURLGV IRU
UHVSLUDWRU\RURWKHULQGLFDWLRQVLIXQVXUHGLVFXVVZLWKWKHPHGLFDOPRQLWRUSULRUWR
VFUHHQLQJ DW9LVLW
 6XEMHFWV WUHDWHG E\ WKH PRQRFORQDO DQWLERG\ RPDOL]XPDE ;RODLU DW 9LVLW 
7UHDWPHQWZLWK;RODLULVQRW DOORZHGGXULQJWKHVWXG\
 6XEMHFWVLQYROYHGLQRWKHUFOLQLFDOWULDOV DW9LVLW
 $IILOLDWLRQ ZLWK ,QYHVWLJDWRU 6LWH ,V DQ LQYHVWLJDWRU VXELQYHVWLJDWRU VWXG\
FRRUGLQDWRU HPSOR\HH RI D SDUWLFLSDWLQJ LQYHVWLJDWRU RU VWXG\ VLWH RU LPPHGLDWH
IDPLO\PHPEHURIWKHDIRUHPHQWLRQHGWKDWLVLQYROYHGLQWKLVVWXG\

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
32
 6XEMHFWVZKRSODQWRPRYHDZD\IURPWKHJHRJUDSKLFDODUHDZKHUHWKHVWXG\LV
EHLQJFRQGXFWHGGXULQJWKHVWXG\

6FUHHQLQJ%DVHOLQH)DLOXUHV
$WRWDORIVXEMHFWVZLOOEHVFUHHQHGDVVXEMHFWVDUHSODQQHGWREHUDQGRPLVHGDQG
RIVFUHHQIDLOXUHLVH[SHFWHG
! 6FUHHQIDLOXUHVDUHGHILQHGDVVXEMHFWVZKRFRQVHQWWRSDUWLFLSDWHLQWKHFOLQLFDO
WULDO EXW DUH QHYHU VXEVHTXHQWO\ UDQGRPL]HG ,Q RUGHU WR HQVXUH WUDQVSDUHQW
UHSRUWLQJ RI VFUHHQ IDLOXUH VXEMHFWV PHHW WKH &RQVROLGDWHG 6WDQGDUGV RI
5HSRUWLQJ7ULDOV&216257SXEOLVKLQJUHTXLUHPHQWVDQGUHVSRQGWRTXHULHV
IURP 5HJXODWRU\ DXWKRULWLHV D PLQLPDO VHW RI VFUHHQ IDLOXUH LQIRUPDWLRQ LV
UHTXLUHGLQFOXGLQJ'HPRJUDSK\6FUHHQ)DLOXUHGHWDLOV(OLJLELOLW\&ULWHULDDQG
DQ\6HULRXV$GYHUVH(YHQWVUHODWHGWRVWXG\SDUWLFLSDWLRQ

:LWKGUDZDO6WRSSLQJ &ULWHULD

6XEMHFWV/RVWWR)ROORZXS
7KHIROORZLQJDFWLRQVPXVWEHWDNHQLQUHODWLRQWRDVXEMHFWZKRIDLOVWRDWWHQGWKHFOLQLF
IRUDUHTXLUHGVWXG\YLVLW
!
7KHVLWHPXVWDWWHPSWWRFRQWDFWWKHVXEMHFWDQGUHVFKHGXOHWKHPLVVHGYLVLWDVVRRQ
DVSRVVLEOH
!
7KHVLWHPXVWFRXQVHOWKHVXEMHFWRQWKHLPSRUWDQFHRIPDLQWDLQLQJWKHDVVLJQHGYLVLW
VFKHGXOHDQGDVFHUWDLQZKHWKHURUQRWWKHVXEMHFWZLVKHVWRDQGRUVKRXOGFRQWLQXHLQ
WKHVWXG\
!
,QFDVHVZKHUHWKHVXEMHFWLVGHHPHGµORVWWRIROORZXS¶WKHLQYHVWLJDWRURUGHVLJQHH
PXVWPDNHHYHU\HIIRUWWRUHJDLQFRQWDFWZLWKWKHVXEMHFWZKHUHSRVVLEOH
WHOHSKRQHFDOOVDQGLIQHFHVVDU\DFHUWLILHGOHWWHUWRWKHVXEMHFW¶VODVWNQRZQPDLOLQJ
DGGUHVVRUORFDOHTXLYDOHQWPHWKRGV7KHVHFRQWDFWDWWHPSWVVKRXOGEHGRFXPHQWHG
LQWKHVXEMHFW¶VPHGLFDOUHFRUG
!
6KRXOGWKHVXEMHFWFRQWLQXHWREHXQUHDFKDEOHRQO\WKHQZLOOKHVKHEHFRQVLGHUHGWR
KDYHZLWKGUDZQIURPWKHVWXG\ZLWKDSULPDU\UHDVRQRI³/RVWWR)ROORZXS´

6XEMHFW:LWKGUDZDOE\,QYHVWLJDWRURU6HOIZLWKGUDZDO
6XEMHFWVPD\EHZLWKGUDZQIURPVWXG\WUHDWPHQWDWDQ\WLPHE\WKH,QYHVWLJDWRULILWLV
FRQVLGHUHGWREHGHWULPHQWDOIRUWKHPWRFRQWLQXHWKHVWXG\WUHDWPHQWRUPD\GLVFRQWLQXH
DVXEMHFWIURPWKHVWXG\DWKLVRUKHUGLVFUHWLRQ,IDVXEMHFWZLWKGUDZVIURPWKHVWXG\
KHVKHPD\UHTXHVWGHVWUXFWLRQRIDQ\VDPSOHVWDNHQDQGWKHLQYHVWLJDWRUPXVWGRFXPHQW
WKLVLQWKHVLWHVWXG\UHFRUGV
7KHIROORZLQJFULWHULDZLOOFDXVHDVXEMHFWWREHZLWKGUDZQIURPLQYHVWLJDWLRQDOSURGXFW
,3EXWHYHU\HIIRUWVKRXOGEHPDGHWRNHHSWKH6XEMHFWLQWKHVWXG\

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
33
!
$VXEMHFWEHFRPHVSUHJQDQW
!
$VXEMHFWPHHWVWKH/LYHU6WRSSLQJ&ULWHULDDVGHILQHGLQ6HFWLRQ
!
$VXEMHFWPHHWVWKH47FVWRSSLQJFULWHULDDVGHILQHGLQ6HFWLRQ
,IWKHVXEMHFWFKRRVHVWRZLWKGUDZIURPWKHVWXG\DOOVWXG\UHODWHGPHGLFDWLRQVDQGRWKHU
VWXG\UHODWHGPDWHULDOVVKRXOGEHUHWXUQHGWRWKHVLWHE\WKHVXEMHFW$Q(DUO\:LWKGUDZDO
9LVLWVKRXOGEHFRQGXFWHGZLWKLQKRXUVRIWKHVXEMHFWVWRSSLQJVWXG\PHGLFDWLRQ
6HFWLRQ 7LPHDQG(YHQW7DEOH,QWKHHYHQWDVXEMHFWZLWKGUDZVDWRUGXULQJD
VFKHGXOHGYLVLWDQ(DUO\:LWKGUDZDO9LVLWLVQRWUHTXLUHGKRZHYHUDOOVWXG\SURFHGXUHV
VFKHGXOHGDWDQ(DUO\:LWKGUDZDO9LVLWPXVWEHSHUIRUPHGDWWKLVYLVLWLQVWHDG
7KHSULPDU\UHDVRQIRUVWXG\WUHDWPHQWGLVFRQWLQXDWLRQRUVWXG\ZLWKGUDZDOZLOOEH
UHFRUGHGLQWKHHOHFWURQLF&DVH5HSRUW)RUPH&5)DQGDQ\GDWDFROOHFWHGXSXQWLOWKH
SRLQWRIZLWKGUDZDOZLOOEHXVHGLQWKHGDWDDQDO\VHV
6SHFLILFUHJDUGVKRXOGEHJLYHQWRGLVWLQJXLVKLQJZLWKGUDZDOVGXHWR$'5V 6$(VDQG
SURWRFRO GHYLDWLRQ IROORZLQJ FRQVXOWDWLRQ ZLWK WKH PHGLFDO PRQLWRU 7KH ,QYHVWLJDWRU
ZLOOUHFRUGWKHSULPDU\UHDVRQLQWKHH&5)
6XEMHFWVZLWKGUDZQIURPWKHVWXG\ZLOOQRWEHUHSODFHG
6XEMHFWV ZKR H[SHULHQFH DQ DVWKPD H[DFHUEDWLRQ GXULQJ WKH 7UHDWPHQW 3HULRG FDQ
FRQWLQXHLQWKHVWXG\DWWKHGLVFUHWLRQRIWKHLU,QYHVWLJDWRU

/LYHU&KHPLVWU\6WRSSLQJ&ULWHULD
/LYHUFKHPLVWU\VWRSSLQJDQGLQFUHDVHGPRQLWRULQJFULWHULD KDYHEHHQGHVLJQHGWR
DVVXUHVXEMHFWVDIHW\DQGHYDOXDWHOLYHUHYHQW HWLRORJ\ LQDOLJQPHQWZLWKWKH)'$
SUHPDUNHWLQJFOLQLFDOOLYHUVDIHW\JXLGDQFH
KWWSZZZIGDJRYGRZQORDGV'UXJV*XLGDQFH&RPSOLDQFH5HJXODWRU\,QIRUPDWLRQ*XLG
DQFHV8&0SGI

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
34
3KDVH,,,,9/LYHU&KHPLVWU\6WRSSLQJDQG,QFUHDVHG0RQLWRULQJ$OJRULWKP
Continue Study Treatment 
Discontinue Study Treatment 
3OXV
Bilirubin≥2x
ULN (>35% 
direct) RUSOXV
INR>1.5, if 
measured*
3RVVLEOH
+\¶V /DZ
ALT≥3xULN
ALT
≥8xULN
3OXV
Symptoms of 
liver injury
or 
hypersensitivity
No
Yes
Yes
Yes
No
No
No
See algorithm 
for continued 
therapy with 
increased liver 
chemistry 
monitoring
Yes
*INR value not applicable to subjects on anticoagulants 
ALT 
≥3xULN 
but 
<8xULN
Yes
 0XVWUHIHUWR/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWVVHFWLRQLQWKH$SSHQGL[
 5HSRUWDVDQ6$(LISRVVLEOH+\¶V /DZFDVHALT≥3xULN DQGBilirubin≥2xULN (>35% direct)  RU
INR>1.5, if measured*

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
35
3KDVH,,,,9/LYHU&KHPLVWU\,QFUHDVHG0RQLWRULQJ$OJRULWKPZLWK&RQWLQXHG
7KHUDS\IRU$/7∀[8/1EXW[8/1
/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWV6HFWLRQFDQEHIRXQGLQ
$SSHQGL[

6WXG\7UHDWPHQW5HVWDUWRU 5HFKDOOHQJH
6WXG\WUHDWPHQWUHVWDUWRUUHFKDOOHQJHDIWHUOLYHUFKHPLVWU\VWRSSLQJFULWHULDDUHPHWE\
DQ\VXEMHFWSDUWLFLSDWLQJLQWKLVVWXG\LVQRWDOORZHG

47F6WRSSLQJ&ULWHULD
$Q(&*LVQRWUHTXLUHGSULRUWRHQWHULQJWKLVVWXG\7KHUHDUHQRRWKHUUHJXODU(&*V
UHTXLUHGE\WKLVSURWRFRO,IKRZHYHUZKLOHDVXEMHFWLVUHFHLYLQJVWXG\PHGLFDWLRQDQ
(&*LVSHUIRUPHGDVSDUWRIWKHQRUPDOFOLQLFDOSUDFWLFHDQGDSURORQJHG47LQWHUYDOLV
GHWHFWHG WKH IROORZLQJ DVVHVVPHQWV IRU ZLWKGUDZDO IURP WKH VWXG\ DUH UHTXLUHG DIWHU
GLVFXVVLRQEHWZHHQ,QYHVWLJDWRUDQGWKHPHGLFDOPRQLWRU
Continue Study Treatment   and   Monitor Liver Chemistry
Discontinue Study Treatment 
ALT≥5xULN 
but <8xULN
+ bili <2xULN +
no symptoms
No
 0XVWUHIHUWR/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWVVHFWLRQLQWKH$SSHQGL[
Yes
ALT ≥3xULN 
but <5xULN
+ bili <2xULN  +
no symptoms
Able to 
monitor  
weekly 
for  ≥2 
weeks
Persists for 
≥2 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
No
No
Able to 
monitor  
weekly 
for  ≥4 
weeks
Persists for 
≥4 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
Yes
ALT ≥5xULN 
ALT <5xULN 
Yes
Yes
*INR value not applicable to subjects on anticoagulants 
 0XVWUHIHUWR/LYHU6DIHW\5HTXLUHG$FWLRQVDQG)ROORZXS$VVHVVPHQWVVHFWLRQLQWKH$SSHQGL[
 5HSRUWDVDQ6$(LISRVVLEOH+\¶V /DZFDVHALT≥3xULN DQGBilirubin≥2xULN (>35% direct)  RU
INR>1.5, if measured*

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
36
)RUDOOVXEMHFWV
$VXEMHFWZKRPHHWVHLWKHURIWKHEXOOHWHGFULWHULDEHORZZLOOEHZLWKGUDZQIURPWKH
VWXG\
!
47F!PVHF258QFRUUHFWHG 47!PVHF
!
,QFUHDVHLQ47F!PVHFGHWHFWHGFRPSDUHGWRDSUHYLRXV(&*
)RUSDWLHQWVZLWKXQGHUO\LQJEXQGOHEUDQFKEORFNIROORZWKHGLVFRQWLQXDWLRQFULWHULD
OLVWHGEHORZ
%DVHOLQH47FZLWK%XQGOH%UDQFK%ORFN
'LVFRQWLQXDWLRQ47FZLWK%XQGOH
%UDQFK%ORFN
PVHF
!PVHF
± PVHF
PVHF
7KH47FVKRXOGEHEDVHGRQVLQJOHRUDYHUDJHG47FYDOXHVRIWULSOLFDWH
HOHFWURFDUGLRJUDPVREWDLQHGRYHUDEULHIHJPLQXWHUHFRUGLQJSHULRG

6XEMHFWDQG6WXG\&RPSOHWLRQ
$FRPSOHWHGVXEMHFWLVRQHZKRKDVFRPSOHWHG DOOVWXG\YLVLWV 7KHHQGRIWKHVWXG\LV
GHILQHGDVWKHODVWVXEMHFW¶VODVWYLVLW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
37

678'<75($70(17

,QYHVWLJDWLRQDO3URGXFWDQG2WKHU6WXG\7UHDWPHQW
7KHWHUPµVWXG\WUHDWPHQW¶LVXVHGWKURXJKRXWWKHSURWRFROWRGHVFULEHDQ\FRPELQDWLRQ
RISURGXFWVUHFHLYHGE\WKHVXEMHFWDVSHUWKHSURWRFROGHVLJQ6WXG\WUHDWPHQWPD\
WKHUHIRUHUHIHUWRWKHLQGLYLGXDOVWXG\WUHDWPHQWVRUWKHFRPELQDWLRQRIWKRVHVWXG\
WUHDWPHQWV
$OO VXEMHFWV ZLOO UHFHLYH WKH DVWKPD PHGLFDWLRQ WR EH XVHG GXULQJ WKH VWXG\ IURP WKH
LQYHVWLJDWRUVLWH
*OD[R6PLWK.OLQH &OLQLFDO 7ULDOV 6XSSOLHV ZLOO SURYLGH WKH LQYHVWLJDWLRQDO SURGXFWV
))9, 5HOYDU
(OOLSWD
DQG FRPSDUDWLYH WUHDWPHQWV LH 6HUHWLGH
'LVNXV
6\PELFRUW 7XUEXKDOHUDVZHOODVUHVFXHPHGLFDWLRQ6DOEXWDPROIRUXVHLQWKLVVWXG\
1HZ,&6/$%$'3,RU'3,FRSLHVRIH[LVWLQJPDUNHWHG,&6/$%$LIDQ\LQ)UDQFHDW
WKHWLPHRIWKHVWXG\ZLOOQRWEHFRQVLGHUHGLQWKLVWULDO
(DFK VXEMHFW UDQGRPLVHG WR WKH ))9, DUP ZLOO EH LQVWUXFWHG WR DGPLQLVWHU WKH VWXG\
PHGLFDWLRQRQFHGDLO\ E\UHDGLQJWKHOHDIOHWDQGGHPRQVWUDWLRQRILWXVHDWWKHVDPH
WLPHRIWKHGD\IRU WKHGXUDWLRQRIWKHWUHDWPHQWSHULRG(DFKVXEMHFWZLOOEHDGYLVHGWR
DGKHUHWR))9,GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\7KH,QYHVWLJDWRUPD\DGMXVWWKH
GRVHRI))9,DFFRUGLQJWRWKHVXEMHFWV¶UHVSRQVHVWDUWLQJE\))9,PFJPFJ
(DFKVXEMHFWLQLWLDWLQJRWKHU,&6/$%$PDLQWHQDQFHWKHUDS\ZLOOEHUHPLQGHGDERXWWKH
WHFKQLTXHV RI KRZ WR XVH WKHLU PDLQWHQDQFH PHGLFDWLRQ E\ UHDGLQJ WKH OHDIOHW DQG
GHPRQVWUDWLRQRILWXVHDQGWKHFRUUHFWGRVLQJ(DFKVXEMHFWZLOOEHDGYLVHGWRDGKHUHWR
,&6/$%$GRVLQJUHJLPHQWKURXJKRXWWKHVWXG\VWDUWLQJE\)36PFJPFJRUE\
%8') PFJ PFJ DFFRUGLQJ WR WKH ,QYHVWLJDWRU¶V GHFLVLRQ 7KH ,QYHVWLJDWRU PD\
DGMXVWWKHGRVHRIHDFKSURGXFWDFFRUGLQJWRWKHVXEMHFWV¶UHVSRQVH
$GHVFULSWLRQRIWKHLQYHVWLJDWLRQDOWUHDWPHQWVLVSURYLGHGEHORZ
7DEOH
'HVFULSWLRQRI)OXWLFDVRQH)XURDWH9LODQWHURO,QKDODWLRQ3RZGHU'U\
3RZGHU,QKDOHUDQGFRPSDUDWLYHWUHDWPHQWV
&RPSRXQG
)RUPXODWLRQ
)OXWLFDVRQH
)XURDWH9LODQWHURO
)LUVW VWULS ))  PFJ RU  PFJ EOHQGHG ZLWK
ODFWRVH
6HFRQGVWULS9LODQWHURO PFJEOHQGHGZLWKODFWRVH
DQGPDJQHVLXPVWHDUDWH
'RVDJH)RUP
'3,(OOLSWD ± GRVHVSHUGHYLFH
8QLW'RVH6WUHQJWK
 PFJ PFJRU PFJ PFJSHUDFWXDWLRQ
5RXWHRI$GPLQLVWUDWLRQ
,QKDOHG
 PDJQHVLXPVWHDUDWH PZZRIWRWDOGUXJSURGXFW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
38
&RPSRXQG
)RUPXODWLRQ
)OXWLFDVRQHSURSLRQDWH6DOPHWHURO
)3 PFJRU PFJEOHQGHGZLWKODFWRVH
6DOPHWHURO PFJEOHQGHGZLWKODFWRVH
'RVDJH)RUP
'3,'LVNXV± GRVHVSHUGHYLFH
8QLW'RVH6WUHQJWK
 PFJ PFJRU PFJPFJSHUDFWXDWLRQ
5RXWHRI$GPLQLVWUDWLRQ
,QKDOHG
&RPSRXQG
)RUPXODWLRQ
%XGHVRQLGH)RUPRWHURO)XPDUDWH
%XGHVRQLGH  PFJ RU  PFJ  EOHQGHG ZLWK
ODFWRVH
)RUPRWHURO)XURDWHPFJRUPFJEOHQGHGZLWK
ODFWRVH
'RVDJH)RUP
'3,7XUEXKDOHU RUGRVHV PFJ PFJRU
PFJPFJSHUGHYLFH
8QLW'RVH6WUHQJWK
 PFJPFJRU PFJ PFJSHUDFWXDWLRQ
5RXWHRI$GPLQLVWUDWLRQ
,QKDOHG
7KHVXEMHFW¶VXVHRIVKRUWUDSLGDFWLQJEHWDDJRQLVWEURQFKRGLODWRUZLOOEHDVVHVVHGDVLW
ZRXOGEHLQURXWLQHFDUHDQGLIUHTXLUHGUHVFXHPHGLFDWLRQZLOOEHSUHVFULEHGWRVXEMHFWV
WRXVHDVQHHGHGWKURXJKRXWWKHVWXG\IRUUHOLHIRIDVWKPDV\PSWRPVDVSHUXVXDOSUDFWLFH

0HGLFDO'HYLFHV
0HGLFDOGHYLFHVVSLURPHWHUVZLOOEHSURYLGHGE\*6.IRUXVHLQWKLVVWXG\+RZHYHU
QRQHRIWKHGHYLFHVSURYLGHGDUHPDQXIDFWXUHGE\RURQEHKDOIRI*6.

7UHDWPHQW$VVLJQPHQW
6XEMHFWV ZLOO EH DVVLJQHG WR VWXG\ WUHDWPHQW LQ DFFRUGDQFH ZLWK WKH UDQGRPLVDWLRQ
VFKHGXOH
6XEMHFWVZLOOEHUDQGRPL]HGWRRQHRIWKHIROORZLQJWUHDWPHQWJURXSV

))9,DVSHUGRVHJXLGDQFHEHORZ

,QLWLDWH RQ XVXDO LQKDOHG GU\ SRZGHU ,&6/$%$ IL[HG FRPELQDWLRQ IRU DVWKPD
PDLQWHQDQFH WKHUDS\ LH 6HUHWLGH 'LVNXV RU 6\PELFRUW 7XUEXKDOHU DFFRUGLQJ WR
XVXDOSK\VLFLDQ¶VSUHVFULSWLRQ
'RVH*XLGDQFH
)RUVXEMHFWVUDQGRPLVHGWR))9,,QYHVWLJDWRUFDQPDNHGRVLQJGHFLVLRQEDVHGRQWKH
JXLGDQFHEHORZ

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
39
!
))9,  PFJPFJ GRVH RQFH D GD\ LV DSSUR[LPDWHO\ HTXLYDOHQW WR IOXWLFDVRQH
SURSLRQDWHVDOPHWHURO
)36
PHGLXP
GRVH

PFJPFJ
DQG
WR
EXGHVRQLGHIRUPRWHURO %8') PHGLXP GRVH  PFJ PFJ WZLFH D GD\ 6HH
7DEOH IRU IXUWKHUJXLGDQFHIRUGRVHVFRQYHUVLRQIRURWKHUFRUWLFRVWHURLGV
!
))9, PFJ PFJGRVHRQFHDGD\LVDSSUR[LPDWHO\HTXLYDOHQWWRIOXWLFDVRQH
SURSLRQDWHVDOPHWHURO KLJK GRVH  PFJ PFJ DQG WR EXGHVRQLGHIRUPRWHURO
KLJK GRVH  PFJ PFJ WZLFH D GD\ 6HH 7DEOH  IRU JXLGDQFH IRU GRVH
FRQYHUVLRQIRURWKHUFRUWLFRVWHURLGV
!
6WDUWLQJGRVHVDUH PFJ PFJRQFHGDLO\ IRU))9, PFJPFJWZLFHGDLO\
IRU)36DQG PFJPFJWZLFHGDLO\IRU%8')
7DEOH
,&6/$%$'DLO\'RVH6P3&6HUHWLGH'LVNXV6\PELFRUW
7XUEXKDOHU
)RUPXODWLRQ
,QKDOHU'HYLFHV
'RVHV$YDLODEOHPFJ
,&6/$%$DQG
,QKDODWLRQVGD\
)OXWLFDVRQH
SURSLRQDWHVDOPHWHURO
'3, 'LVNXV
LQKDODWLRQ[
0HGLXPGRVH
+LJKGRVH
%XGHVRQLGHIRUPRWHURO
'3, 7XUEXKDOHU
LQKDODWLRQV[
0HGLXPGRVH
+LJKGRVH
,QIRUPDWLRQH[WUDFWHGIURP*,1$ UHIHUWR*,1$IRUIXUWKHUJXLGDQFH
)RU SDWLHQWV ZLWK PRGHUDWH WR VHYHUH KHSDWLF LPSDLUPHQW WKH  PLFURJUDPV GRVH
VKRXOG EH XVHG DQG SDWLHQWV VKRXOG EH PRQLWRUHG IRU V\VWHPLF FRUWLFRVWHURLGUHODWHG
DGYHUVHUHDFWLRQVVHH6P3&

3ODQQHG'RVH$GMXVWPHQWV
6XEMHFWVUDQGRPLVHGWRWKHXVXDO,&6/$%$DVWKPDPDLQWHQDQFHWKHUDS\DUPFDQKDYH
WKHLU WUHDWPHQW DGMXVWHG DV ZRXOG EH QRUPDO FOLQLFDO SUDFWLFH DW WKH ,QYHVWLJDWRU¶V
GLVFUHWLRQ 7KLV ZLOO QRW UHTXLUH WKH VXEMHFW WR EH ZLWKGUDZQ IURP WKH VWXG\ 7KHVH
VXEMHFWVVKRXOGQRWUHFHLYH))9,LIWKHPHGLFDWLRQLVPDUNHWHGGXULQJWKHVWXG\SHULRG
6XEMHFWV UDQGRPL]HG WR WKH ))9, DUP DQG IRU ZKRP LW LV FRQVLGHUHG DSSURSULDWH
QHFHVVDU\WRDGMXVWWUHDWPHQWFDQKDYHWKHLUUHJLPHQFKDQJHGDVUHTXLUHGDVSHUQRUPDO
FOLQLFDO SUDFWLFH DW DQ\ SRLQW LQ WKH VWXG\ DQG WKH VXEMHFW FRXOG UHPDLQ LQ WKH VWXG\

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
40
6XEMHFWVRQ))9,DUPFDQDOVRFKDQJHEHWZHHQWKHWZR))9,GRVHVDVDSSURSULDWHDQG
DWWKH,QYHVWLJDWRU¶VGLVFUHWLRQ

%OLQGLQJ
7KLVVWXG\LVDQRSHQODEHOUDQGRPLVHGVWXG\

3DFNDJLQJDQG /DEHOLQJ
7KHFRQWHQWVRIWKHODEHOZLOOEHLQDFFRUGDQFHZLWKDOODSSOLFDEOHUHJXODWRU\
UHTXLUHPHQWV

3UHSDUDWLRQ+DQGOLQJ6WRUDJH$FFRXQWDELOLW\
$OO))9, DQGFRPSDUDWLYH,&6/$%$PDLQWHQDQFHWKHUDS\SUHVFULEHGWKURXJKRXWWKH
VWXG\ZLOOEH GLVSHQVHGDWDQGFROOHFWHGIURPWKHLQYHVWLJDWRUVLWH
,QYHVWLJDWLRQDOSURGXFW PXVW EHVWRUHGLQDVHFXUHDUHDXQGHU WKHDSSURSULDWHSK\VLFDO
FRQGLWLRQVIRUWKHSURGXFW$OO'3,VFRQWDLQLQJ))9,PXVWEHVWRUHGDWDWHPSHUDWXUHRI
XSWR&%XGHVRQLGH)RUPRWHURODQG)OXWLFDVRQH3URSLRQDWH6DOPHWHURO'3,VPXVWEH
VWRUHGDWDWHPSHUDWXUHRIXSWR&
$FFHVV WR DQG DGPLQLVWUDWLRQ RI WKH LQYHVWLJDWLRQDO SURGXFW ZLOO EH OLPLWHG WR WKH
LQYHVWLJDWRU DQG DXWKRULVHG VLWH VWDII ,QYHVWLJDWLRQDO SURGXFW PXVW EH GLVSHQVHG RU
DGPLQLVWHUHGRQO\WRVXEMHFWVHQUROOHGLQWKHVWXG\DQGLQDFFRUGDQFHZLWKWKHSURWRFRO
$OO XVHG DQG XQXVHG VWXG\ PHGLFDWLRQ LQKDOHUV ))9, RU XVXDO ,&6/$%$ DVWKPD
PDLQWHQDQFHWKHUDS\VKRXOGEHUHWXUQHGWRWKHLQYHVWLJDWRUVLWHZKHQWKHVXEMHFWVFROOHFW
SUHVFULSWLRQVRIVWXG\PHGLFDWLRQ
$WWKHHQGRIWKHVWXG\DOOVWXG\VXSSOLHGVWXG\PHGLFDWLRQXVHGDQGXQXVHGZLOOEH
GHVWUR\HGIROORZLQJORFDOVWDQGDUGRSHUDWLQJSURFHGXUHVH[FHSWZKHUHLWLVVXVSHFWHGWKDW
(OOLSWD RU *6. '3, SDFNDJLQJ LV GHIHFWLYH 7KH GHYLFH DQG SDFNDJLQJ VKRXOG EH
UHWXUQHGWR*6.
'HWDLOVIRUERWKUHWXUQDQGGHVWUXFWLRQDQGRIVWXG\PHGLFDWLRQDUHIRXQGLQWKH6WXG\
3URFHGXUH0DQXDO630
8QGHUQRUPDOFRQGLWLRQVRIKDQGOLQJDQGDGPLQLVWUDWLRQLQYHVWLJDWLRQDOSURGXFWLVQRW
H[SHFWHGWRSRVHVLJQLILFDQWVDIHW\ULVNVWRVLWHVWDII7DNHDGHTXDWHSUHFDXWLRQVWRDYRLG
GLUHFWH\HRUVNLQFRQWDFWDQGWKHJHQHUDWLRQRIDHURVROVRUPLVWV1RWLI\WKHPRQLWRURI
DQ\ XQLQWHQWLRQDO RFFXSDWLRQDO H[SRVXUH $ 0DWHULDO 6DIHW\ 'DWD 6KHHW 06'6
GHVFULELQJ WKH RFFXSDWLRQDO KD]DUGV DQG UHFRPPHQGHG KDQGOLQJ SUHFDXWLRQV ZLOO EH
SURYLGHGWRVLWHVWDIILIUHTXLUHGE\ORFDOODZVRUZLOORWKHUZLVHEHDYDLODEOHIURP*6.
XSRQUHTXHVW
,QDFFRUGDQFHZLWKORFDOUHJXODWRU\UHTXLUHPHQWVWKH,QYHVWLJDWRUGHVLJQDWHGVLWHVWDII
RU KHDG RI WKH PHGLFDO LQVWLWXWLRQ ZKHUH DSSOLFDEOH PXVW GRFXPHQW WKH DPRXQW RI
LQYHVWLJDWLRQDO SURGXFW GLVSHQVHG DQGRU DGPLQLVWHUHG WR VWXG\ VXEMHFWV WKH DPRXQW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
41
UHWXUQHGE\VWXG\VXEMHFWVDQGWKHDPRXQWUHFHLYHGIURP DQGUHWXUQHGWR*6.ZKHQ
DSSOLFDEOH3URGXFWDFFRXQWDELOLW\UHFRUGVPXVWEHPDLQWDLQHGWKURXJKRXWWKHFRXUVHRI
WKHVWXG\

&RPSOLDQFH ZLWK6WXG\7UHDWPHQW$GPLQLVWUDWLRQ
:KHQWKHVXEMHFWVDWWHQGWKHLQYHVWLJDWRUVLWHWKH\ZLOOEHLQVWUXFWHGWRDGPLQLVWHUWKH
VWXG\PHGLFDWLRQRQFHGDLO\DWWKHVDPHWLPHRIWKHGD\IRUWKHGXUDWLRQRIWKHWUHDWPHQW
ZKHQUDQGRPLVHGWR))9,YLD(OOLSWD70 DQGWZLFHGDLO\RQWKHPRUQLQJDQGHYHQLQJ
ZKHQ UDQGRPLVHG WR ,&6/$%$ '3, 'LVNXV70 RU 7XUEXKDOHU $OO XVHG DQG XQXVHG
VWXG\ PHGLFDWLRQ LQKDOHUV ))9, RU XVXDO DVWKPD PDLQWHQDQFH WKHUDS\ VKRXOG EH
UHWXUQHG WR WKH LQYHVWLJDWRU VLWH ZKHQ WKH VXEMHFWV FROOHFW SUHVFULSWLRQV RI VWXG\
PHGLFDWLRQ
7UHDWPHQW DGKHUHQFH ZLWK VWXG\ PHGLFDWLRQ ZLOO EH DVVHVVHG EDVHG RQ DQDO\VLV RI
PHGLFDWLRQV GLVSHQVHG DQG FROOHFWHG GXULQJ WKH VWXG\ DQG RQ 0HGLFDWLRQ $GKHUHQFH
5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDWUDQGRPLVDWLRQ'D\DW:HHN
DQGDW:HHN

7UHDWPHQWRI6WXG\7UHDWPHQW2YHUGRVH
$QRYHUGRVHZLOOEHGHILQHGDVWKH VXEMHFWUHFHLYLQJDQ\DPRXQWRI,3JUHDWHUWKDQWKH
PD[LPXPGRVHSHUPLWWHGE\WKHSURWRFROZKLFKUHVXOWVLQFOLQLFDOVLJQVRUV\PSWRPV
,Q WKH HYHQW RI DQ RYHUGRVH RI VWXG\ PHGLFDWLRQ WKH ,QYHVWLJDWRU VKRXOG XVH FOLQLFDO
MXGJPHQWLQWUHDWLQJWKHRYHUGRVHDQGFRQWDFWWKHVWXG\PHGLFDOPRQLWRU
*OD[R6PLWK.OLQH*6.LVQRWUHFRPPHQGLQJVSHFLILFWUHDWPHQWJXLGHOLQHVIRURYHUGRVH
DQGWR[LFLW\PDQDJHPHQW7KH,QYHVWLJDWRUVKRXOGUHIHUWRWKHUHOHYDQWGRFXPHQWVIRU
GHWDLOHGLQIRUPDWLRQUHJDUGLQJZDUQLQJVSUHFDXWLRQVFRQWUDLQGLFDWLRQVDGYHUVHHYHQWV
DQG RWKHU VLJQLILFDQW GDWD SHUWDLQLQJ WR WKH VWXG\ GUXJ EHLQJ XVHG LQ WKLV VWXG\ 6XFK
GRFXPHQWVPD\LQFOXGHEXWQRWEHOLPLWHGWRWKH,%VRUHTXLYDOHQWGRFXPHQWSURYLGHG
E\*6.IRUVWXG\PHGLFDWLRQV

7UHDWPHQWDIWHUWKH(QGRIWKH6WXG\
7KHLQYHVWLJDWRULVUHVSRQVLEOHIRUHQVXULQJWKDWFRQVLGHUDWLRQKDVEHHQJLYHQWRWKHSRVW
VWXG\FDUHRIWKHSDWLHQW¶VPHGLFDOFRQGLWLRQZKHWKHURUQRW*6.LVSURYLGLQJVSHFLILF
SRVWVWXG\WUHDWPHQW

&RQFRPLWDQW0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
$OO UHVSLUDWRU\UHODWHGSUHVFULEHGDQGGLVSHQVHGFRQFRPLWDQWPHGLFDWLRQVWDNHQGXULQJ
WKHVWXG\ZLOOEHUHFRUGHG7KHPLQLPXPUHTXLUHPHQWLVWKDWGUXJWUDGHQDPHDQGWKH
GDWHVRISUHVFULELQJGLVSHQVLQJDQGFROOHFWLRQZLOOEHUHFRUGHG

2017N339371_00

2014N190259_00 
&21),'(17,$/
 
 
 
HZA116492 
 
42 
 

3HUPLWWHG0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
$OOPHGLFDWLRQVIRUDVWKPDDQGRWKHUGLVRUGHUVWKDWDUHQRWFRQWUDLQGLFDWHGLQDVWKPDRU
OLVWHGDVDSURKLELWHGPHGLFDWLRQVHH6HFWLRQPD\EHFRQWLQXHGWKURXJKRXWWKH
VWXG\
$W FOLQLFDO GRVHV ORZ SODVPD FRQFHQWUDWLRQV RI )) DQG 9, DUH DFKLHYHG DIWHU LQKDOHG
GRVLQJGXHWRH[WHQVLYHILUVWSDVVPHWDEROLVPDQGKLJKV\VWHPLFFOHDUDQFHPHGLDWHGE\
F\WRFKURPH3$LQWKHJXWDQGRUOLYHUDQ\FOLQLFDOO\VLJQLILFDQWGUXJLQWHUDFWLRQV
PHGLDWHGE\))RU9,DUHXQOLNHO\
$ &<3$ GUXJ LQWHUDFWLRQ VWXG\ ZDV SHUIRUPHG LQ KHDOWK\ VXEMHFWV ZLWK WKH ))9,
FRPELQDWLRQDQG.HWRFRQD]ROH&RDGPLQLVWUDWLRQLQFUHDVHGPHDQ))$8&
 DQG &PD[ E\  DQG  UHVSHFWLYHO\ 7KH LQFUHDVH LQ )) H[SRVXUH ZDV
DVVRFLDWHG ZLWK D  UHGXFWLRQ LQ  K ZHLJKWHG PHDQ VHUXP FRUWLVRO &R
DGPLQLVWUDWLRQLQFUHDVHGPHDQ9,$8&W¶DQG&PD[DQGUHVSHFWLYHO\7KH
LQFUHDVH LQ 9, H[SRVXUH ZDV QRW DVVRFLDWHG ZLWK DQ LQFUHDVH LQ EHWDDJRQLVW UHODWHG
V\VWHPLFHIIHFWVRQKHDUWUDWHEORRGSRWDVVLXPRU47F)LQWHUYDO
&DUH LV DGYLVHG ZKHQ FRDGPLQLVWHULQJ SRWHQW F\WRFKURPH 3 $ LQKLELWRUV HJ
NHWRFRQD]ROHULWRQDYLUDVWKHUHLVSRWHQWLDOIRUDQLQFUHDVHGV\VWHPLFH[SRVXUHWRERWK
))DQG9,&RQVLGHUDWLRQVKRXOGEHJLYHQWRWKHFOLQLFDOVLWXDWLRQDQGWKHGXUDWLRQRI
WUHDWPHQWZLWKVXFKFRQFXUUHQWPHGLFDWLRQV

3URKLELWHG0HGLFDWLRQVDQG1RQ'UXJ7KHUDSLHV
• 6\VWHPLFFRUWLFRVWHURLGVH[FHSWLQFDVHRIDVHYHUHDVWKPDH[DFHUEDWLRQ
• 0RQRFORQDODQWLERG\RPDOL]XPDE;RODLU


678'<$66(660(176$1'352&('85(6
7KH7LPHDQG(YHQWV7DEOHLVSURYLGHGLQ6HFWLRQ$OOVWXG\DVVHVVPHQWVVKRXOGEH
FRQGXFWHGE\WKH,QYHVWLJDWRURUKLVKHUTXDOLILHGGHVLJQHHXQOHVVRWKHUZLVHVSHFLILHGLQ
WKHSURWRFRORU6303OHDVHUHIHUWRWKH630IRUWKHVXJJHVWHGRUGHURIDVVHVVPHQWV

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
43

7LPHDQG(YHQWV7DEOH
Study Visits
Visit 1*
Screening
Visit 2*
Randomisation
Visit 3
Phone 
call 1
Visit 
4**
Visit 5
Phone 
call 2
Visit 6
Early 
Withdrawal
Study week (± specified 
no. of days)
'D\WR

'D\
:HHN
 
GD\V
:HHN


GD\V
:HHN
 
GD\V
:HHN


GD\V
Early 
Withdrawal
Visit 
x
x
x
x
x
Phone interview 
x
x
Assessments
,QIRUPHG&RQVHQW
x
(OLJLELOLW\ FULWHULD
x
x
'HPRJUDSK\
x
6PRNLQJVWDWXV
x
0HGLFDO)DPLO\ KLVWRU\ RI
FRQVHQWHGVXEMHFWV LQFOXGLQJ
&9
5LVN
IDFWRUV
DQG
H[DFHUEDWLRQKLVWRU\
x
3*[VDOLYDVDPSOH
x
3K\VLFDOH[DPLQDWLRQ
x
x
x
x
x
Safety Assessments
8ULQH3UHJQDQF\7HVW
x
x
x
x
([DFHUEDWLRQ$VVHVVPHQW
x
x
x
x
x
x
9LWDOVLJQV
x
x
x
x
x
6HULRXV $GYHUVH (YHQW DQG
$GYHUVH
'UXJ
5HDFWLRQ
$VVHVVPHQW
x
x
x
x
x
x
Efficacy Assessments
6SLURPHWU\
7HVWLQJ
3UH
GRVHWURXJK)(9
x
x
x 
Subject Questionnaires 
$VWKPD&RQWURO7HVW
x
x
x
x
x
x
x
(4'
x
x
x
$VWKPD4XDOLW\RI
/LIH4XHVWLRQQDLUH
x
x
x
0$56$TXHVWLRQQDLUH
x
x
x
x
3DWLHQW
6DWLVIDFWLRQ
DQG
3UHIHUHQFH3$6$34
x
x
Inhaler 
correct 
use 
assessment
7\SH$RYHUDOOHUURUVUHFRUG
x
x
x
Medication Assessments
&RQFRPLWDQW
0HGLFDWLRQ
$VVHVVPHQW
x
x
x
x
x
'LVSHQVH6WXG\0HGLFDWLRQð
x
x
&ROOHFW6WXG\0HGLFDWLRQð
x
x
x
RAMOS/eCRF
5$0261*
x
x
H&5)
x
x
x
x
x
x
x

6$(DQG$'5PRQLWRULQJZLOORFFXUIURP'D\6$(UHODWHGWRVWXG\SDUWLFLSDWLRQVKRXOGEHJLQIURPVLJQLQJRI
,&)$QDGGLWLRQDOVDIHW\DQG$&7FKHFNLVSURYLGHGE\SKRQHDWZHHNDQG

7KURXJKRXWWKHVWXG\WKHVWXG\PHGLFDWLRQZLOOEHGLVSHQVHGDQGFROOHFWHGE\WKHLQYHVWLJDWRUVLWH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
44
9LVLWDQG9LVLWFDQEHFRPELQHGLIWKHVXEMHFWGLGQRWWDNHKLVXVXDODVWKPDPHGLFDWLRQEHIRUHFRPLQJRQVLWH
7KHQWKLVYLVLWZLOOEH'D\DQGDOOEDVHOLQHFKDUDFWHULVWLFVZLOOEHFROOHFWHGDWWKLVYLVLW :ULWWHQ,QIRUPHG&RQVHQWPXVW
EHREWDLQHGSULRUWRLQLWLDWLRQRIVWXG\SURFHGXUHVRULQLWLDWLQJFKDQJHVLQPHGLFDWLRQV
 9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW 5DQGRPLVDWLRQYLVLW
3*[VDOLYDVDPSOHFROOHFWHGDW9LVLW5DQGRPLVDWLRQRUDQ\VFKHGXOHGFOLQLFYLVLWWKHUHDIWHU
 2QO\ LIHDUO\ZLWKGUDZDORFFXUV EHIRUH:HHN
2QO\IRUFKLOGEHDULQJZRPHQ

6FUHHQLQJDQG&ULWLFDO%DVHOLQH$VVHVVPHQWV
7KHIROORZLQJGHPRJUDSKLFSDUDPHWHUVZLOOEHFDSWXUHG\HDURIELUWKVH[DQGHWKQLFLW\
0HGLFDOPHGLFDWLRQIDPLO\KLVWRU\ZLOOEHDVVHVVHGDVUHODWHGWRWKHLQFOXVLRQH[FOXVLRQ
FULWHULDOLVWHGLQ6HFWLRQ DQGDVLQGLFDWHGLQWKHWLPHDQGHYHQWWDEOH
&DUGLRYDVFXODUPHGLFDOKLVWRU\&9ULVNIDFWRUVDQGH[DFHUEDWLRQKLVWRU\ZLOOEHDVVHVVHG
DVLQGLFDWHGLQWKHWLPHDQGHYHQWWDEOH
6PRNLQJVWDWXVZLOOEHDOVRFDSWXUHG DVIROORZQRQVPRNHUFXUUHQWRUIRUPHUFLJDUHWWH
VPRNHUV )RUPHUVPRNHUVZLOOEHGHILQHGDVWKRVHZKRKDYHVWRSSHGVPRNLQJIRUDWOHDVW
PRQWKVSULRUWR9LVLW RU9LVLWLIWKHYLVLWDQGDUHFRPELQHG1XPEHURISDFN
\HDUVVKRXOGEHDVVHVVHG DWVFUHHQLQJ9LVLWQXPEHURISDFN\HDUV QXPEHURI
FLJDUHWWHVSHUGD\[QXPEHURI\HDUVVPRNHGHJFLJDUHWWHVSHUGD\IRU
\HDUVRUFLJDUHWWHVSHUGD\IRU\HDUV
3URFHGXUHVFRQGXFWHGDVSDUWRIWKHVXEMHFW¶V URXWLQHFOLQLFDOPDQDJHPHQW>HJEORRG
FRXQW@DQGREWDLQHGSULRUWRVLJQLQJRILQIRUPHGFRQVHQWPD\EHXWLOL]HGIRU6FUHHQLQJRU
EDVHOLQHSXUSRVHVSURYLGHGWKHSURFHGXUHPHHWVWKHSURWRFROGHILQHGFULWHULDDQGKDV
EHHQSHUIRUPHGLQWKHWLPHIUDPHRIWKHVWXG\
$&7 ZLOOEHDVVHVVHGDWVFUHHQLQJ9LVLWDQGUDQGRPLVDWLRQ9LVLW $4/46(4
'DQG0$56$ZLOOEHDVVHVVHGDW9LVLW5DQGRPLVDWLRQ7KHVH3DWLHQW5HSRUWHG
2XWFRPHVTXHVWLRQQDLUHVVKRXOGEHFRPSOHWHGE\VXEMHFWVEHIRUHDQ\RWKHUDVVHVVPHQW DW
DFOLQLFYLVLWLQWKHRUGHUVSHFLILHG7KHFRUUHFWXVHRILQKDOHUZLOOEHDVVHVVHGDOVRDW
UDQGRPL]DWLRQYLVLW9LVLW
DIWHUUHDGLQJWKHSDFNDJHLQVHUWRISURGXFWE\WKHSDWLHQWDQG
 DIWHU GHPRQVWUDWLRQ RI LW XVH E\ WKH LQYHVWLJDWRU $Q\ FULWLFDO HUURUV ZLOO EH
UHJLVWHUHGE\WKH,QYHVWLJDWRUZKHQXVLQJHDFKGHYLFH
%DVHOLQH SUHGRVH )(9 ZLOO EH DVVHVVHG DW WKLV YLVLW E\ WKH ,QYHVWLJDWRU XVLQJ D
VSLURPHWHUSURYLGHGE\*6.5HVFXHPHGLFDWLRQVDOEXWDPROZLOOEHVWRSSHGKRXUV
EHIRUH EDVHOLQH VSLURPHWU\ DQG XVXDO DVWKPD PHGLFDWLRQ ZLOO EH QRW EH WDNHQ E\ WKH
SDWLHQWEHIRUHFRPLQJRQVLWH
1R VWXG\ UHODWHG SURFHGXUHV PD\ EH SHUIRUPHG XQWLO WKH LQIRUPHG FRQVHQW IRUP
GRFXPHQWKDVEHHQUHYLHZHGZLWKDQGVLJQHGE\WKHVXEMHFW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
45

(IILFDF\
6HH6HFWLRQ IRUWKHHIILFDF\HQGSRLQWVDQG 6HFWLRQ IRUWKHSURSRVHGWLPHDQGHYHQWV
WDEOH

,QKDOHU&RUUHFW8VH$VVHVVPHQW
&RUUHFWXVHRIWKHLQKDOHUZLOOEHDVVHVVHGDVRXWOLQHGLQWKH7LPHDQG(YHQWV7DEOH
6HFWLRQ
7DEOH
/LVWRI7\SH$OLNHO\WREHFULWLFDODQGRYHUDOOHUURUV IRU(OOLSWDTM
7\SH$HUURUV IRU(OOLSWD70
\HV
QR
2YHUDOOHUURUV IRU(OOLSWD70
\HV
QR
)DLOHG WRRSHQFRYHU
1R
H[KDODWLRQ
EHIRUH
DQ
LQKDOLQJ
([KDOHG GLUHFWO\LQWRPRXWKSLHFH
%ORFNHG
DLU
LQOHW
GXULQJ
LQKDODWLRQPDQRHXYUH
6KRRNWKHGHYLFHXSVLGHGRZQDIWHU
GRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUH

ORQJ

VWHDG\

GHHS
,QKDODWLRQ IURP PRXWKSLHFH NHSW
EHWZHHQOLSV
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
'LGQRWKROGEUHDWK
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHH
WH[WER[@
7DEOH
/LVW7\SH$ OLNHO\WREHFULWLFDODQGRYHUDOO HUURUV IRU'LVNXVTM
7\SH$HUURUVIRU'LVNXV70
\HV
QR
2YHUDOOHUURUVIRU'LVNXV70
\HV
QR
)DLOHG WRRSHQFRYHU
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
/HYHULVQRWSXVKHGEDFN
,QKDODWLRQPDQRHXYUH

VWHDG\

GHHS
([KDOHGGLUHFWO\ LQWRPRXWKSLHFH
'LGQRWKROGEUHDWK
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
46
7\SH$HUURUVIRU'LVNXV70
\HV
QR
2YHUDOOHUURUVIRU'LVNXV70
\HV
QR
PHGLFDWLRQWKDWLVLQKDOHG
$Q\RWKHUFRPPHQWV>IUHH
WH[WER[@

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
47
7DEOH
/LVWRI7\SH$OLNHO\WREHFULWLFDOHUURUVDQGRYHUDOOHUURUV IRU
7XUEXKDOHU
7\SH$HUURUVIRU7XUEXKDOHU
\HV
QR
2YHUDOOHUURUVIRU
7XUEXKDOHU
\HV
QR
)DLOHGWRUHPRYHFDS
1RH[KDODWLRQEHIRUHDQ
LQKDODWLRQ
'LGQRWKROGGHYLFHXSULJKW
2.GXULQJGRVHSUHSDUDWLRQ
,QKDODWLRQPDQRHXYUH

IRUFHIXO

GHHS
1RWHWR+&3 LWLVLPSRUWDQW
WKDWWKHLQKDODWLRQLVIRUFHIXO
DQGGHHSIURPWKHVWDUWIRU
WKLVLQKDOHU
%DVHQRWWZLVWHGIXOO\EDFNZDUGV
DQGIRUZDUGVQRFOLFNKHDUG
%ORFNHGDLULQOHWGXULQJ
LQKDODWLRQPDQRHXYUH
6KRRNWKHGHYLFHDIWHUGRVH
SUHSDUDWLRQ
'LGQRWKROGEUHDWK
([KDOHGGLUHFWO\LQWRPRXWKSLHFH
'LGQRWFORVHWKHGHYLFH
1RWH WKLVLVDQHUURUEXW
RQHZKLFKGRHVQRWDIIHFWWKH
PHGLFDWLRQWKDWLVLQKDOHG
1RVHDOE\WKHOLSVURXQGWKH
PRXWKSLHFHGXULQJWKHLQKDODWLRQ
$Q\RWKHUFRPPHQWV>IUHH
WH[WER[@

7URXJK SUHGRVH)(9DVVHVVPHQW
)(9 ZLOOEHPHDVXUHGWRDVVHVVOXQJIXQFWLRQDW9LVLW 5DQGRPLVDWLRQ DQG9LVLW
:HHN  DV RXWOLQHG LQ WKH 7LPH DQG (YHQWV 7DEOH 9LVLW  :HHN  VKRXOG EH
VFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW 5DQGRPLVDWLRQYLVLW0HDVXUHPHQWVVKRXOG
EH WDNHQ SUHGRVH DQG VXEMHFWV VKRXOG EH LQVWUXFWHG QRW WR WDNH WKHLU DVWKPD
PHGLFDWLRQVWXG\GUXJSULRUWRFRPLQJLQWRWKHFOLQLFDWWKHVHYLVLWV6XEMHFWVVKRXOGDOVR
ZLWKKROG IURP XVLQJ WKHLU UHVFXH PHGLFDWLRQ IRU DW OHDVW  KRXUV SULRU WR 9LVLW 
5DQGRPLVDWLRQ DQG9LVLW :HHN
$OO VLWHV ZLOO XVH VWDQGDUGLVHG VSLURPHWU\ HTXLSPHQW SURYLGHG E\ *6. )RU HDFK
REVHUYDWLRQ DW OHDVW  YDOLG ZLWK QR PRUH WKDQ  HIIRUWV ZLOO EH REWDLQHG 7KH EHVW
)(9YDOXHZLOOEHUHFRUGHGLQWKHH&5)
7KH,QYHVWLJDWRUZLOOEHDVNHGWRPDNHHYHU\HIIRUWWRSHUIRUPWKHVSLURPHWU\DWWKHVDPH
WLPHRIWKHGD\DW9LVLWDQGDW 9LVLW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
48

4XHVWLRQQDLUHV

$VWKPD&RQWURO7HVW$&7
7KH $&7 LV D YDOLGDWHG VHOIDGPLQLVWHUHG TXHVWLRQQDLUH XWLOLVLQJ  TXHVWLRQV WR DVVHVV
DVWKPDFRQWUROGXULQJWKHSDVWZHHNVRQDSRLQWFDWHJRULFDOVFDOHWR6XEMHFWV
ZLOO FRPSOHWH WKH $&7 DW 6FUHHQLQJ 9LVLW  DW 5DQGRPLVDWLRQ 9LVLW  DW :HHN 
3KRQH&DOO RU9LVLWDW:HHN9LVLW DW:HHN3KRQH&DOO RU9LVLWDQG
DW:HHN9LVLW (DUO\:LWKGUDZDOYLVLW
$Q $&7 VFRUH RI  WR  VXJJHVWV WKDW WKH VXEMHFW¶V DVWKPD LV XQOLNHO\ WR EH ZHOO
FRQWUROOHG$ VFRUHRI  WR  VXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLV OLNHO\WREHZHOO
FRQWUROOHG
3OHDVHUHIHUWR$SSHQGL[ DQGWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV

$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH$4/46
7KH$4/4LVDGLVHDVHVSHFLILFVHOIDGPLQLVWHUHGTXDOLW\RIOLIHTXHVWLRQQDLUHGHYHORSHG
WRHYDOXDWHWKHLPSDFWRIDVWKPDWUHDWPHQWVRQWKHTXDOLW\RIOLIHRIDVWKPDVXIIHUHUVRYHU
WKHODVWZHHNV>-XQLSHU @$4/46ZLOOEHPHDVXUHGDW5DQGRPLVDWLRQ9LVLW
DW:HHN 9LVLW (DUO\:LWKGUDZDOYLVLW 3OHDVHUHIHUWR$SSHQGL[ DQGWKH6WXG\
3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV

(XUR4RO4XHVWLRQQDLUH (4'/HYHO
*HQHUDOKHDOWKVWDWXVZLOOEHDVVHVVHGZLWKWKH(XUR4RO(4'/HYHO 4XHVWLRQQDLUH
DW5DQGRPLVDWLRQ9LVLW DQGDW:HHN 9LVLW(DUO\:LWKGUDZDOYLVLW
3OHDVHUHIHUWR $SSHQGL[ DQGWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV

0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$
5HSRUWHGDGKHUHQFHWRPHGLFDWLRQZLOOEHDVVHVVHGZLWKWKH0HGLFDWLRQ$GKHUHQFH
5HSRUW6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDW9LVLW:HHN9LVLW DQG
:HHN9LVLW (DUO\:LWKGUDZDOYLVLW
7KH0$56$LVDLWHPTXHVWLRQQDLUHZKHUHPHGLFDWLRQXVHLVUDWHGRQDSRLQW
/LNHUWVFDOHLQGLFDWLQJµDOZD\V¶WRLQGLFDWLQJµQHYHU¶,WKDVEHHQYDOLGDWHGDVDVHOI
UHSRUWHGPHDVXUHRIDGKHUHQFHZLWK,&6IRUVXEMHFWVZLWKDVWKPDDQGLQFOXGHVJHQHULF³,
XVHLWUHJXODUO\HYHU\GD\´DQGOXQJFRQGLWLRQVSHFLILFTXHVWLRQVDERXWPHGLFDWLRQXVH
³,RQO\XVHLWZKHQ,IHHOEUHDWKOHVV´>&RKHQ@7KHUHLVQRVSHFLILHGWLPHIUDPHRQ
ZKLFKUHVSRQVHVVKRXOGEHEDVHG
7KH,QYHVWLJDWRU VKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH0$56$DWWKHVDPHWLPHDW
WKHVSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH0$56$ KDYHQRVSHFLILHG
WLPHIUDPHRQZKLFKUHVSRQVHVVKRXOGEHEDVHG

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
49

3DWLHQWV6DWLVIDFWLRQDQG3UHIHUHQFHZLWKWKHGHYLFH3$6$3
4XHVWLRQQDLUH
7KH3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH3$6$34>&0.R]PD @
LV D PXOWLLWHP PHDVXUH RI UHVSLUDWRU\ LQKDODWLRQ GHYLFH VDWLVIDFWLRQ DQG SUHIHUHQFH
GHVLJQHGWREHHDVLO\XQGHUVWRRGDQGDGPLQLVWHUHGWRSDWLHQWVZLWKDVWKPDDQG&23'
3DWLHQW VDWLVIDFWLRQ ZLWK HDFK GHYLFH DQG GHYLFH SUHIHUHQFH ZLOO EH DVVHVVHG DW
:HHN9LVLW (DUO\:LWKGUDZDOYLVLW LIVXEMHFWLVZLWKGUDZQEHIRUH:HHN9LVLW

7KH,QYHVWLJDWRU VKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH3$6$34DWWKHVDPHWLPHDW
WKHVSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH3$6$34KDVQRVSHFLILHG
WLPHIUDPHRQZKLFKUHVSRQVHVVKRXOGEHEDVHG

6DIHW\
3ODQQHGWLPHSRLQWVIRUDOOVDIHW\DVVHVVPHQWVDUHOLVWHGLQWKH7LPHDQG(YHQWV7DEOH
VHH6HFWLRQ
6HULRXV$GYHUVH(YHQWV6$(DQGQRQVHULRXV$GYHUVH'UXJ5HDFWLRQV$'5 ZLOOEH
FROOHFWHGLQWKLVVWXG\
6DIHW\HQGSRLQWVZLOOLQFOXGH
!
)UHTXHQF\DQGW\SHRIVHULRXVDGYHUVHHYHQWV
!
)UHTXHQF\DQGW\SHRIQRQVHULRXVDGYHUVHGUXJUHDFWLRQVUHODWHGWRWUHDWPHQW

$GYHUVH(YHQWV$( $GYHUVH'UXJ 5HDFWLRQV$'5VDQG
6HULRXV$GYHUVH(YHQWV6$(V
7KHGHILQLWLRQVRIDQ$($'5RU6$(FDQEHIRXQGLQ$SSHQGL[ 
7KHLQYHVWLJDWRUDQGWKHLUGHVLJQHHVDUHUHVSRQVLEOHIRUGHWHFWLQJGRFXPHQWLQJDQG
UHSRUWLQJHYHQWVWKDWPHHWWKHGHILQLWLRQRIDQ$(RU6$($OODGYHUVHHYHQWVZLOOEH
UHFRUGHGLQWKHVRXUFHGRFXPHQWVEXWRQO\LQIRUPDWLRQUHJDUGLQJQRQVHULRXVDGYHUVH
GUXJUHDFWLRQV$'5VDQGVHULRXVDGYHUVHHYHQWV6$(VZLOOEH GRFXPHQWHGDQG
UHSRUWHGLQWKHH&5)

7LPHSHULRGDQG)UHTXHQF\IRUFROOHFWLQJQRQVHULRXV$'5V DQG6$(
LQIRUPDWLRQ
!
$OOQRQVHULRXV$'5VDQG6$(VZLOOEHFROOHFWHGIURPWKHVWDUWRI6WXG\7UHDWPHQW
XQWLOWKHHQGRIWKHVWXG\VHH6HFWLRQ DWWKHWLPHSRLQWVVSHFLILHGLQWKH
7LPHDQG(YHQWV7DEOH6HFWLRQ
!
0HGLFDORFFXUUHQFHVWKDWEHJLQSULRUWRWKHVWDUWRIVWXG\WUHDWPHQWEXWDIWHU
REWDLQLQJLQIRUPHGFRQVHQWPD\EHUHFRUGHGRQWKH0HGLFDO+LVWRU\&XUUHQW
0HGLFDO&RQGLWLRQVVHFWLRQRIWKH&5)

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
50
!
$Q\6$(VDVVHVVHGDVUHODWHGWRVWXG\SDUWLFLSDWLRQHJSURWRFROPDQGDWHG
SURFHGXUHVLQYDVLYHWHVWVRUFKDQJHLQH[LVWLQJWKHUDS\RUUHODWHGWRD*6.SURGXFW
ZLOOEHUHFRUGHGIURPWKHWLPHDVXEMHFWFRQVHQWVWRSDUWLFLSDWHLQWKHVWXG\XSWRDQG
LQFOXGLQJDQ\IROORZXSFRQWDFW
!
$OO6$(VZLOOEHUHFRUGHGDQGUHSRUWHGWR*6.ZLWKLQKRXUVDVLQGLFDWHGLQ
$SSHQGL[ 
!
,QYHVWLJDWRUVDUHQRWREOLJDWHGWR DFWLYHO\VHHN$(VRU6$(VLQIRUPHUVWXG\
VXEMHFWV+RZHYHULIWKHLQYHVWLJDWRUOHDUQVRIDQ\6$(LQFOXGLQJDGHDWKDWDQ\
WLPHDIWHUDVXEMHFWKDVEHHQGLVFKDUJHGIURPWKHVWXG\DQGKHVKHFRQVLGHUVWKH
HYHQWUHDVRQDEO\UHODWHGWRWKHVWXG\WUHDWPHQW RUVWXG\SDUWLFLSDWLRQWKHLQYHVWLJDWRU
PXVWSURPSWO\QRWLI\*6.
127(7KHPHWKRGRIUHFRUGLQJHYDOXDWLQJDQGDVVHVVLQJFDXVDOLW\RI$(VDQG6$(V
SOXVSURFHGXUHVIRUFRPSOHWLQJDQGWUDQVPLWWLQJ6$(UHSRUWVWR*6.DUHSURYLGHGLQ
$SSHQGL[ 

0HWKRGRI'HWHFWLQJQRQVHULRXV$'5VDQG6$(V
7KH,QYHVWLJDWRURUVLWHVWDIIZLOOEHUHVSRQVLEOHIRUGHWHFWLQJGRFXPHQWLQJDQGUHSRUWLQJ
HYHQWVWKDWPHHWWKHGHILQLWLRQRIDQRQVHULRXVDGYHUVHGUXJUHDFWLRQ$'5RUVHULRXV
DGYHUVHHYHQWV6$(
7KHPHWKRGRIGHWHFWLQJUHFRUGLQJHYDOXDWLQJDQGIROORZXSRI6$(VDQGQRQVHULRXV
$'5VSOXVSURFHGXUHVIRUFRPSOHWLQJDQGWUDQVPLWWLQJ6$(UHSRUWVWR*6.DUHSURYLGHG
LQWKH6303URFHGXUHVIRUSRVWVWXG\6$(VQRQVHULRXV$'5VDUHSURYLGHGLQWKH630
&DUHZLOOEHWDNHQQRWWRLQWURGXFHELDVZKHQGHWHFWLQJ$(VDQGRU6$(V2SHQHQGHG
DQGQRQOHDGLQJYHUEDOTXHVWLRQLQJRIWKHVXEMHFWLVWKHSUHIHUUHGPHWKRGWRLQTXLUHDERXW
$(RFFXUUHQFH$SSURSULDWHTXHVWLRQVLQFOXGH
!
³+RZDUH\RXIHHOLQJ"´³+DYH\RXKDGDQ\RWKHUPHGLFDOSUREOHPVVLQFH\RXU
ODVWYLVLWFRQWDFW"´³+DYH\RXWDNHQDQ\QHZPHGLFLQHVRWKHUWKDQWKRVHSURYLGHG
LQWKLVVWXG\VLQFH\RXUODVWYLVLWFRQWDFW"´
3RWHQWLDO6$(VDQGQRQVHULRXV$'5VPD\EHLGHQWLILHGE\KRVSLWDOLVDWLRQDOHUWVWKURXJK
WKHPHGLFDOUHFRUG7KH,QYHVWLJDWRUZLOOKDYHWKHXOWLPDWHUHVSRQVLELOLW\IRUGHWHUPLQLQJ
FDXVDOLW\DQGVHULRXVQHVV

)ROORZXSRIQRQVHULRXV$'5VDQG6$(V
$IWHUWKHLQLWLDOQRQVHULRXV$'5V6$(UHSRUWWKHLQYHVWLJDWRULVUHTXLUHGWRSURDFWLYHO\
IROORZHDFKVXEMHFWDWVXEVHTXHQWYLVLWVFRQWDFWV$OO6$(VDQGQRQVHULRXV$'5VZLOO
EHIROORZHGXQWLOUHVROXWLRQXQWLOWKHFRQGLWLRQVWDELOL]HVXQWLOWKHHYHQWLVRWKHUZLVH
H[SODLQHGRUXQWLOWKHVXEMHFWLVORVWWRIROORZXSDVGHILQHGLQ6HFWLRQ)XUWKHU
LQIRUPDWLRQRQIROORZXSSURFHGXUHVLVJLYHQLQ$SSHQGL[ 

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
51

&DUGLRYDVFXODUDQG'HDWK(YHQWV
)RUDQ\FDUGLRYDVFXODUHYHQWVGHWDLOHGLQ$SSHQGL[  DQGDOOGHDWKVZKHWKHURUQRWWKH\
DUHFRQVLGHUHG6$(VVSHFLILF&DUGLRYDVFXODU&9DQG'HDWKVHFWLRQVRIWKH&5)ZLOO
EHUHTXLUHGWREHFRPSOHWHG 7KHVHVHFWLRQVLQFOXGHTXHVWLRQVUHJDUGLQJFDUGLRYDVFXODU
LQFOXGLQJVXGGHQFDUGLDFGHDWKDQGQRQFDUGLRYDVFXODUGHDWK
7KH&9&5)VDUHSUHVHQWHGDVTXHULHVLQUHVSRQVHWRUHSRUWLQJRIFHUWDLQ&90HG'5$
WHUPV 7KH&9LQIRUPDWLRQVKRXOGEHUHFRUGHGLQWKHVSHFLILFFDUGLRYDVFXODUVHFWLRQRI
WKH&5)ZLWKLQRQHZHHNRIUHFHLSWRID &9(YHQWGDWDTXHU\SURPSWLQJLWVFRPSOHWLRQ
7KH'HDWK&5)LVSURYLGHGLPPHGLDWHO\DIWHUWKHRFFXUUHQFHRURXWFRPHRIGHDWKLV
UHSRUWHG,QLWLDODQGIROORZXSUHSRUWVUHJDUGLQJGHDWKPXVWEHFRPSOHWHGZLWKLQ RQH
ZHHNRIZKHQWKHGHDWKLVUHSRUWHG

'LVHDVH5HODWHG(YHQWVDQGRU'LVHDVH5HODWHG2XWFRPHV1RW
4XDOLI\LQJDV6$(V
$Q\ FOLQLFDOO\ VLJQLILFDQW VDIHW\ DVVHVVPHQWV WKDW DUH DVVRFLDWHG ZLWK WKH XQGHUO\LQJ
GLVHDVH XQOHVV MXGJHG E\ WKH ,QYHVWLJDWRU WR EH PRUH VHYHUH WKDQ H[SHFWHG IRU WKH
VXEMHFW¶VFRQGLWLRQDUHQRW WREHUHSRUWHGDVQRQVHULRXV$'5VRU6$(V

5HJXODWRU\5HSRUWLQJ5HTXLUHPHQWVIRU6$(V
3URPSW QRWLILFDWLRQ RI 6$(V E\ WKH ,QYHVWLJDWRU WR *6. LV HVVHQWLDO VR WKDW OHJDO
REOLJDWLRQVDQGHWKLFDOUHVSRQVLELOLWLHVWRZDUGVWKHVDIHW\RIVXEMHFWVDQGWKHVDIHW\RID
SURGXFW XQGHU FOLQLFDO LQYHVWLJDWLRQ DUH PHW 7KLV ZLOO DOVR LQFOXGH SRWHQWLDO 6$(V
LGHQWLILHGE\KRVSLWDOLVDWLRQDOHUWVWKURXJKWKHPHGLFDOUHFRUG
*6. KDV D OHJDO UHVSRQVLELOLW\ WR QRWLI\ ERWK WKH ORFDO UHJXODWRU\ DXWKRULW\ DQG RWKHU
UHJXODWRU\DJHQFLHVDERXWWKHVDIHW\RIDSURGXFWXQGHUFOLQLFDOLQYHVWLJDWLRQ*6.ZLOO
FRPSO\ZLWKFRXQWU\VSHFLILFUHJXODWRU\UHTXLUHPHQWVUHODWLQJWRVDIHW\UHSRUWLQJWRWKH
UHJXODWRU\DXWKRULW\,QGHSHQGHQW(WKLFV&RPPLWWHH,(&DQG,QYHVWLJDWRUV
,QYHVWLJDWRU VDIHW\ UHSRUWV DUH SUHSDUHG IRU VXVSHFWHG XQH[SHFWHG VHULRXV DGYHUVH
UHDFWLRQVDFFRUGLQJWRORFDOUHJXODWRU\UHTXLUHPHQWVDQG*6.SROLF\DQGDUHIRUZDUGHG
WRLQYHVWLJDWRUVDVQHFHVVDU\
$Q,QYHVWLJDWRUZKRUHFHLYHVDQLQYHVWLJDWRUVDIHW\UHSRUWGHVFULELQJD6$(VRURWKHU
VSHFLILFVDIHW\LQIRUPDWLRQHJVXPPDU\RUOLVWLQJRI6$(VIURP*6.ZLOOILOHLWZLWK
WKH,%DQGZLOOQRWLI\WKH,(&LIDSSURSULDWHDFFRUGLQJWRORFDOUHTXLUHPHQWV
7KHPHWKRGRIGHWHFWLQJUHFRUGLQJHYDOXDWLQJDQGIROORZXSRI6$(VDQGQRQVHULRXV
$'5VSOXVSURFHGXUHVIRUFRPSOHWLQJDQGWUDQVPLWWLQJ6$(UHSRUWVWR*6.DUH SURYLGHG
LQWKH6303URFHGXUHVIRUSRVWVWXG\6$(VQRQVHULRXV$'5VDUHSURYLGHGLQWKH630

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
52
3URFHGXUHV IRU GRFXPHQWLQJ WUDQVPLWWLQJ DQG IROORZXS RI PHGLFDO GHYLFH LQFLGHQWV
DORQJZLWKWKHUHJXODWRU\UHSRUWLQJUHTXLUHPHQWVIRUPHGLFDOGHYLFHVDUHSURYLGHGLQWKH
630

3UHJQDQF\
!
'HWDLOVRIDOOSUHJQDQFLHVLQIHPDOHVXEMHFWVZLOOEHFROOHFWHGIURPWKHWLPHWKH
LQIRUPHGFRQVHQWLVVLJQHG9LVLWDQGXQWLOWKHHQGRIWKHVWXG\9LVLW
!
$Q\SUHJQDQF\WKDWRFFXUVGXULQJVWXG\SDUWLFLSDWLRQPXVWEHUHSRUWHGXVLQJD
FOLQLFDOWULDOSUHJQDQF\IRUP
!
,IDSUHJQDQF\LVUHSRUWHGWKHQWKHLQYHVWLJDWRUVKRXOGLQIRUP*6.ZLWKLQ
ZHHNVRIOHDUQLQJRIWKHSUHJQDQF\DQGVKRXOGIROORZWKHSURFHGXUHVRXWOLQHGLQ
$SSHQGL[
!
$Q\6$(RFFXUULQJLQDVVRFLDWLRQZLWKDSUHJQDQF\EURXJKWWRWKHLQYHVWLJDWRU¶V
DWWHQWLRQDIWHUWKHVXEMHFWKDVFRPSOHWHGWKHVWXG\DQGFRQVLGHUHGE\WKH
LQYHVWLJDWRUDVSRVVLEO\UHODWHGWRWKHVWXG\WUHDWPHQWPXVWEHSURPSWO\UHSRUWHG
WR*6.

0HGLFDO'HYLFH,QFLGHQWV,QFOXGLQJ0DOIXQFWLRQV
0HGLFDOGHYLFHV VSLURPHWHUV ZLOOEHSURYLGHGE\*6.IRUXVHLQWKLVVWXG\ +RZHYHU
QRQHRIWKHGHYLFHVSURYLGHGDUHPDQXIDFWXUHGE\RURQEHKDOIRI*6.

3K\VLFDO([DPV
$FRPSOHWHSK\VLFDOH[DPLQDWLRQZLOOLQFOXGHDWDPLQLPXPDVVHVVPHQW RIWKH
&DUGLRYDVFXODU5HVSLUDWRU\*DVWURLQWHVWLQDODQG1HXURORJLFDOV\VWHPV
,QYHVWLJDWRUVVKRXOGSD\VSHFLDODWWHQWLRQWRFOLQLFDOVLJQVUHODWHGWRSUHYLRXVVHULRXV
LOOQHVVHV

9LWDO6LJQV
9LWDOVLJQPHDVXUHPHQWVZLOOLQFOXGHKHLJKWZHLJKWSXOVHUDWHV\VWROLFDQGGLDVWROLF
EORRGSUHVVXUH
9LWDOVLJQV ZLOOEHPHDVXUHG DQGUHFRUGHGLQWKHH&5) DW6FUHHQLQJYLVLW9LVLWDWWKH
5DQGRPLVDWLRQ9LVLW'D\DW:HHN9LVLWDW:HHN9LVLWDQGDW(DUO\
:LWKGUDZDO9LVLW H[FHSWIRUKHLJKWDQGZHLJKWWKDWZLOOEHFROOHFWHGDW9LVLWRQO\

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
53

(OHFWURFDUGLRJUDP(&*
$Q(&*LVQRWUHTXLUHGSULRUWRHQWHULQJWKLVVWXG\7KHUHDUHQRRWKHUUHJXODU(&*V
UHTXLUHGE\WKLVSURWRFRO

&OLQLFDO 6DIHW\/DERUDWRU\$VVHVVPHQWV
$Q\ DEQRUPDO ODERUDWRU\ WHVW UHVXOWV KHPDWRORJ\ FOLQLFDO FKHPLVWU\ RU XULQDO\VLV RU
RWKHU VDIHW\ DVVHVVPHQWV HJ (&*V UDGLRORJLFDO VFDQV YLWDO VLJQV PHDVXUHPHQWV
LQFOXGLQJ WKRVH WKDW ZRUVHQ IURP EDVHOLQH DQG IHOW WR EH FOLQLFDOO\ VLJQLILFDQW LQ WKH
PHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKH ,QYHVWLJDWRUDUHWREHUHFRUGHGDVQRQVHULRXV
$'5VRU6$(VDVDSSURSULDWH

*HQHWLFV
,QIRUPDWLRQUHJDUGLQJJHQHWLFUHVHDUFKLVLQFOXGHGLQ$SSHQGL[

'$7$0$1$*(0(17
!
)RUWKLVVWXG\VXEMHFW GDWDZLOOEHHQWHUHGLQWR*6.GHILQHG&5)VWUDQVPLWWHG
HOHFWURQLFDOO\WR*6.RUGHVLJQHHDQGFRPELQHGZLWKGDWDSURYLGHGIURPRWKHU
VRXUFHVLQDYDOLGDWHGGDWDV\VWHP
!
0DQDJHPHQWRIFOLQLFDOGDWDZLOOEHSHUIRUPHGLQDFFRUGDQFHZLWKDSSOLFDEOH*6.
VWDQGDUGVDQGGDWDFOHDQLQJSURFHGXUHVWRHQVXUHWKHLQWHJULW\RIWKHGDWDHJ
UHPRYLQJHUURUVDQGLQFRQVLVWHQFLHVLQWKHGDWD
!
$GYHUVHHYHQWVDQGFRQFRPLWDQWPHGLFDWLRQVWHUPVZLOOEHFRGHGXVLQJ0HG'5$
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV DQGDQ LQWHUQDOYDOLGDWHGPHGLFDWLRQ
GLFWLRQDU\*6.'UXJ
!
&5)VLQFOXGLQJTXHULHVDQGDXGLWWUDLOVZLOOEHUHWDLQHGE\*6.DQGFRSLHVZLOOEH
VHQWWRWKHLQYHVWLJDWRUWRPDLQWDLQDVWKHLQYHVWLJDWRUFRS\6XEMHFWLQLWLDOVZLOOQRW
EHFROOHFWHGRUWUDQVPLWWHGWR*6.DFFRUGLQJWR*6.SROLF\

67$7,67,&$/&216,'(5$7,216 $1''$7$
$1$/<6(6

+\SRWKHVHV
7KHREMHFWLYHRIWKHVWXG\LVWRFRPSDUHWKHHIILFDF\RIIOXWLFDVRQHIXURDWH))YLODQWHURO
9, ,QKDODWLRQ 3RZGHU ))9,  PFJPFJ RU ))9,  PFJPFJ ZLWK XVXDO
,&6/$%$LQKDODWLRQGU\SRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\RYHUVL[PRQWKVLQD
ODUJH)UHQFKSULPDU\DQUHVSLUDWRU\VSHFLDOLVWFDUHSRSXODWLRQRIVXEMHFWVZLWKDVWKPD
7KH SULPDU\ HQGSRLQW LV GHILQHG DV WKH FKDQJH IURP EDVHOLQH LQ WKH $&7 WRWDO VFRUH
DVVHVVHGDW:HHN9LVLW 5HJDUGLQJWKHSULPDU\HIILFDF\HQGSRLQWLHWKHFKDQJH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
54
IURPEDVHOLQHLQWKH$&7WRWDOVFRUHDVVHVVHGDW:HHN>9LVLW@WKHSULPDU\DQDO\VLV
ZLOOVKRZWKDWWKHIL[HGFRPELQDWLRQ))9,PFJPFJRUPFJPFJLVQRQ
LQIHULRU WR DQ\ RWKHU ,&6/$%$ FRPELQDWLRQV LQ LQKDODWLRQ SRZGHU DVVXPLQJ D QRQ
LQIHULRULW\PDUJLQRI1RQLQIHULRULW\ZLOOEHFODLPHGLIWKHWZRVLGHGFRQILGHQFH
LQWHUYDORQWKHGLIIHUHQFHLQPHDQSULPDU\HIILFDF\HQGSRLQWV))9,PLQXV&RPSDUDWRU
SUHFOXGHVWKHQRQLQIHULRULW\PDUJLQRI
,IDQGRQO\LIQRQLQIHULRULW\LVVLJQLILFDQWO\DFKLHYHGDW:HHN 9LVLW ZLWKUHJDUG
WR WKH SULPDU\ HQGSRLQW WKHQ QRQLQIHULRULW\ RI WKH IL[HG FRPELQDWLRQ ))9,
PFJPFJRUPFJPFJWRDQ\RWKHU,&6/$%$FRPELQDWLRQV ZLOOEHWHVWHGDW
:HHN9LVLW FRQVLGHULQJWKHVDPHQRQLQIHULRULW\ PDUJLQRI  1RQLQIHULRULW\
ZLOO EH FODLPHG LI WKH  WZRVLGHG FRQILGHQFH LQWHUYDO RQ WKH GLIIHUHQFH LQ PHDQ
SULPDU\HIILFDF\HQGSRLQWV))9,PLQXV&RPSDUDWRUDW:HHN9LVLWSUHFOXGHVWKH
QRQLQIHULRULW\PDUJLQRI
2I QRWH DV WKH WZR WHVWV IRU QRQLQIHULRULW\ DUH VHTXHQWLDOO\ SHUIRUPHG WKH FORVXUH
SULQFLSOHKROGVDQGWKHUHLVQRQHHGWRDGMXVWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
LHIRUHDFKWHVW

6DPSOH6L]H&RQVLGHUDWLRQV

6DPSOH6L]H$VVXPSWLRQV
5HVXOWVEDVHGRQWKH+=$VWXG\KDYHVKRZQWKDWWKHHVWLPDWHGVWDQGDUGGHYLDWLRQ
RIWKHFKDQJHLQ$&7VFRUHZDV8QSXEOLVKHGGDWDKDYHVKRZQWKDWWKHVWDQGDUG
GHYLDWLRQRIFKDQJHRI$&7UDQJHGIURPWR7KHUHIRUHDVRPHZKDWFRQVHUYDWLYH
FKRLFHRI6'RISRLQWLVUHWDLQHG
%DVHGRQWKHOLWHUDWXUH>6FKDW]@WKH0LQLPDOO\,PSRUWDQW'LIIHUHQFH0,'RIWKH
$&7FRXOGEHFRQVLGHUHGDV SRLQWV+DOIWKLV0,'LHFRXOGWKHUHIRUHEHXVHGWR
GHILQHWKHQRQLQIHULRULW\PDUJLQ
$VVXPLQJDSRLQWVWDQGDUGGHYLDWLRQIRUWKHFKDQJHLQ$&7WRWDOVFRUHDW:HHN
9LVLWDSRLQWQRQLQIHULRULW\PDUJLQDQGDWZRVLGHGQRPLQDOVLJQLILFDQFHOHYHO
RIWKHVDPSOHVL]HQHHGHGSHUJURXSWRDFKLHYHDWOHDVWDSRZHULVLHD
WRWDO RI  VXEMHFWV $VVXPLQJ D  GURSRXW UDWH DURXQG  VXEMHFWV PXVW EH
UDQGRPL]HGHLWKHUWR))9,RUWRWKHDOWHUQDWLYH,&6/$%$LQUDWLR WRDFKLHYHDWOHDVW
DSRZHU

6DPSOH6L]H6HQVLWLYLW\
7RGHPRQVWUDWHWKHVHQVLWLYLW\RIWKHVDPSOHVL]HFDOFXODWLRQIRUWKLVVWXG\WKHIROORZLQJ
WDEOHSUHVHQWVWKHSRZHURIWKHVWXG\XQGHUGLIIHUHQWFLUFXPVWDQFHVLQWHUPVRIWKH
VWDQGDUGGHYLDWLRQ

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
55
7KHDVVXPSWLRQXVHGLVVKDGHG
6WDQGDUGGHYLDWLRQ
3RZHUIRUWKHVXEMHFWVHYDOXDEOH
1 











6DPSOH6L]H5HHVWLPDWLRQ RU$GMXVWPHQW
1RWSODQQHG

'DWD$QDO\VLV&RQVLGHUDWLRQV

$QDO\VLV3RSXODWLRQV
3RSXODWLRQVFRQVLGHUHGIRUDQDO\VLVDUHDVIROORZV
,QWHQWWRWUHDW,77VHW$OOUDQGRPL]HGVXEMHFWVKDYLQJUHFHLYHGDWOHDVWRQHGRVH
RIWKHSUHVFULSWLRQRIVWXG\PHGLFDWLRQ HLWKHU))9,RUXVXDO,&6/$%$DVWKPD
PDLQWHQDQFH WKHUDS\ 7KH ,77 VHW ZLOO EH XVHG WR DQDO\]H WKH SULPDU\ HIILFDF\
HQGSRLQW DQDO\VLV WKH VHFRQGDU\ HIILFDF\ HQGSRLQW DQG RWKHU HIILFDF\ HQGSRLQWV
6XEMHFWVZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVUDQGRPL]HGIRUWKH,77VHW
3HUSURWRFRO 33 VHW DOO ,77 VXEMHFWV ZLWKRXW DQ\ PDMRU YLRODWLRQV RI VWXG\
SURFHGXUHV 0DMRU SURWRFRO YLRODWLRQV ZLOO EH LGHQWLILHG SULRU WR GDWDEDVH ORFN
3URWRFROGHYLDWLRQVZLOOEHUHYLHZHGDQGFODVVLILHGDVPLQRURUPDMRUGXULQJDGDWD
UHYLHZPHHWLQJWKDWZLOOEHKHOGEHIRUHGDWDEDVHORFN7KHH[FOXVLRQRIVXEMHFWV
IURPWKH33VHWZLOOEHVSHFLILHGDQGGRFXPHQWHGLQWKH5$3
6DIHW\ VHW $OO HQUROOHG VXEMHFWV KDYLQJ UHFHLYHG DW OHDVW RQH GRVH RI WKH
SUHVFULSWLRQ RI VWXG\ PHGLFDWLRQ HLWKHU ))9, RU XVXDO ,&6/$%$ DVWKPD
PDLQWHQDQFHWKHUDS\DQGFRQVLGHUHGDVWUHDWHG7KH6DIHW\VHWZLOOEHWKHEDVLVIRU
VDIHW\DQDO\VHV6XEMHFWVZLOOEHDVVLJQHGWRWKHWUHDWPHQWJURXSDVWUHDWHGIRUWKH
6DIHW\VHW
'HWDLOVRIWKHDQDO\VLVGDWDVHWVWREHFUHDWHGZLOOEHVSHFLILHGLQWKH5HSRUW$QDO\VLV3ODQ
5$3

,QWHULP$QDO\VLV
1RWDSSOLFDEOH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
56

.H\(OHPHQWVRI$QDO\VLV3ODQ
7KHSULPDU\FRPSDULVRQRILQWHUHVWLVWKHFRPSDULVRQRIWKHFKDQJHIURPEDVHOLQH 9LVLW
 LQWKHWRWDO$&7VFRUHDVVHVVHGDW:HHN 9LVLWEHWZHHQ))9,PFJPFJRU
PFJPFJ DQG XVXDO ,&6/$%$ LQKDODWLRQ SRZGHU IRU DVWKPD PDLQWHQDQFH
WKHUDS\
7KH SULPDU\ VHW IRU DQDO\VLV LV WKH LQWHQW WR WUHDW VHW $ VHQVLWLYLW\ DQDO\VLV ZLOO EH
SHUIRUPHGLQWKH33VHW
1RQLQIHULRULW\RI))9,WR,&6/$%$ZLOOEHILUVWWHVWHGDWWKHVLGHGQRPLQDOOHYHO
RIVLJQLILFDQFH,I1RQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGWKHQVXSHULRULW\RI))9,WR
,&6/$%$ZLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
,IDQGRQO\LIQRQLQIHULRULW\LVDFKLHYHGIRUWKHSULPDU\HQGSRLQWDW:HHN9LVLW
WKHQWKHNH\VHFRQGDU\ HQGSRLQWLHWKHFKDQJHIURPEDVHOLQHLQWKHWRWDO$&7VFRUH
DVVHVVHG DW:HHN 9LVLWZLOOEHWHVWHG$W:HHN9LVLWQRQLQIHULRULW\RI
))9, WR ,&6/$%$ ZLOO EH ILUVW WHVWHG DW WKH  WZRVLGHG QRPLQDO OHYHO RI
VLJQLILFDQFH,I1RQLQIHULRULW\LVDFKLHYHGWKHQVXSHULRULW\RI))9,WR,&6/$%$ZLOO
VWLOOEHWHVWHGDWWKHWZRVLGHGQRPLQDOOHYHORIVLJQLILFDQFH
2IQRWHWKLVVWHSGRZQWHVWLQJSURFHGXUHVWLOOVWURQJO\FRQWUROVWKHRYHUDOOW\SH,HUURUDW
WKHWZRVLGHGOHYHO
'HILQLWLRQRIWKHWUHDWPHQWIDLOXUHZLOOEHDVIROORZ
!
7UHDWPHQWZLWKGUDZDO
!
&KDQJHRIWUHDWPHQW
!
'RVHLQFUHDVHEH\RQGWKHPD[LPXPDOORZHGGDLO\GRVHLQWKH(8OLFHQVHIRU
))9,!PFJPFJIRU)36!PFJWZLFHGDLO\IRU%8')!
PFJWZLFHGDLO\
2WKHU &RPSDULVRQV RI ,QWHUHVW 2WKHU HIILFDF\ HQGSRLQWV DQG VDIHW\ HQGSRLQWV ZLOO EH
GHVFULEHG(VWLPDWHGGLIIHUHQFHVEHWZHHQJURXSVZLWKFRQILGHQFHLQWHUYDOVZLOOEH
SURYLGHGZKHQDSSOLFDEOH
'DWD ZLOO EH OLVWHG DQG VXPPDUL]HG DFFRUGLQJ WR WKH *6. UHSRUWLQJ VWDQGDUGV ZKHUH
DSSOLFDEOH&RPSOHWHGHWDLOVZLOOEHGRFXPHQWHGLQWKH5HSRUWLQJ$QDO\VLV3ODQ5$3
$Q\GHYLDWLRQVIURPRUDGGLWLRQVWRWKHRULJLQDODQDO\VLVSODQGHVFULEHGLQWKLVSURWRFRO
ZLOO EH GRFXPHQWHG LQ WKH 5$3 DQG ILQDO VWXG\ UHSRUW 'HVFULSWLYH VXPPDULHV ZLOO EH
SURYLGHGE\WUHDWPHQWJURXS
'HPRJUDSKLFDQGEDVHOLQHFKDUDFWHULVWLFVZLOOEHVXPPDUL]HG
&RQWLQXRXVYDULDEOHV ZLOOEHVXPPDUL]HGXVLQJGHVFULSWLYHVWDWLVWLFVQXPEHURIREVHUYHG
DQG PLVVLQJ GDWD PHDQ VWDQGDUG GHYLDWLRQ 6' PHGLDQ 4 4 PLQLPXP DQG
PD[LPXP

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
57
&DWHJRULFDO YDULDEOHV ZLOO EH VXPPDUL]HG DV QXPEHUV RI REVHUYHG DQG PLVVLQJ GDWD
FRXQWVDQG SHUFHQWDJHIRUHDFKFDWHJRU\UHSRUWHGWRWKHQXPEHURIQRQPLVVLQJYDOXHV
)RUELQDU\YDULDEOHVFRQILGHQFHLQWHUYDOVIRUSURSRUWLRQVZLOOEHHVWLPDWHGEDVHGRQ
WKH&ORSSHU3HDUVRQPHWKRG
7KH FRQWUDVW EHWZHHQ ))9, DQG XVXDO ,&6/$%$ DVWKPD PDLQWHQDQFH WKHUDS\ LQ
LQKDODWLRQSRZGHUZLOOEHRISULPDU\LQWHUHVWIRUDOOHIILFDF\HQGSRLQWV
1RQLQIHULRULW\RI))9,YHUVXVXVXDO,&6/$%$DVWKPDWKHUDS\ZLOOEHILUVWWHVWHGDW
:HHN9LVLW,IDQGRQO\LIVLJQLILFDQFH LVDFKLHYHGDW:HHN9LVLWWKHQQRQ
LQIHULRULW\ZLOOEHWHVWHGDW:HHN9LVLWDWWKHWZRVLGHGOHYHORIVLJQLILFDQFH
7KLVVWHSGRZQ WHVWLQJ SURFHGXUHVWURQJO\FRQWUROVWKHRYHUDOOW\SH , HUURUDWWKH
WZRVLGHGOHYHO
,IQRQLQIHULRULW\LVDFKLHYHGDW:HHN 9LVLWWKHQVXSHULRULW\RI))9,YHUVXVXVXDO
,&6/$%$ DVWKPD WKHUDS\ ZLOO EH WHVWHG DW WKH VDPH WZRVLGHG QRPLQDO VLJQLILFDQFH
OHYHO RI  ,I QRQLQIHULRULW\ LV DFKLHYHG DW :HHN  9LVLW  WKHQ VXSHULRULW\ RI
))9, YHUVXV XVXDO ,&6/$%$ DVWKPD WKHUDS\ ZLOO EH WHVWHG DW WKH VDPH WZRVLGHG
QRPLQDOVLJQLILFDQFHOHYHORI
%DVHOLQH$&7VFRUHZLOOEHLQFOXGHGLQWKHSULPDU\HIILFDF\DQDO\VHV*HQGHUDJHVWXG\
VLWH DQG SRWHQWLDOO\ VHDVRQ DW UDQGRPL]DWLRQ ZLOO EH IXUWKHU LQYHVWLJDWHG LQ VHQVLWLYLW\
DQDO\VHV ZKHQ DSSURSULDWH 2WKHU FRYDULDWHV PD\ EH FRQVLGHUHG DQG LI VR LW ZLOO EH
GHWDLOHGLQWKH5$3
7UHDWPHQWE\SURJQRVWLFIDFWRUVLQWHUDFWLRQVZLOOEHVSHFLILFDOO\LQYHVWLJDWHGLQVHFRQGDU\
PRGHOV
+DQGOLQJRIWUHDWPHQWZLWKGUDZDOWUHDWPHQWZLWKGUDZDOZLOOEHFRQVLGHUHGDVDIDLOXUH
DQGWKHSULPDU\HQGSRLQWDWWKHWUHDWPHQWZLWKGUDZDOWLPHZLOOEHDVVHVVHGEDVHGRQWKH
ODVWDYDLODEOH$&7SRVWUDQGRPL]DWLRQVFRUHEHIRUHZLWKGUDZDO2IQRWHDFKDQJHLQWKH
GRVHUHJLPHQZLOOQRWEHFRQVLGHUHGDVDWUHDWPHQWIDLOXUH
+DQGOLQJ RI PLVVLQJ GDWD DV D JHQHUDO UXOH PLVVLQJ GDWD ZLOO QRW EH UHSODFHG
1HYHUWKHOHVVVHQVLWLYLW\DQDO\VHVUHJDUGLQJWKHSULPDU\DQGNH\VHFRQGDU\HQGSRLQWZLOO
UHSODFHPLVVLQJ$&7 DVVHVVPHQWVE\WKHODVWDYDLODEOHSRVWUDQGRPL]DWLRQ$&7YDOXH
LHEDVHGRQWKHODVWREVHUYDWLRQFDUULHGIRUZDUGPHWKRG
7KHVWXG\LVDGHTXDWHO\SRZHUHGIRUWKHSULPDU\DQGWKHNH\VHFRQGDU\HQGSRLQWLHWR
VKRZQRQLQIHULRULW\RI))9,WRFXUUHQW,&6/$%$ DW:HHN9LVLWDQGDW:HHN
9LVLWFRQVLGHULQJDQRQLQIHULRULW\PDUJLQRI2WKHUVHFRQGDU\HQGSRLQWVDUHQRW
QHFHVVDULO\DGHTXDWHO\SRZHUHGDQGDGHVFULSWLYHDQDO\VLVZLOORQO\EHSURSRVHGIRUWKHVH
HQGSRLQWV
7KHSULPDU\HIILFDF\DQDO\VLVSRSXODWLRQVHWLVGHILQHGDVDOOVXEMHFWVEHORQJLQJWRWKH
,QWHQWWR7UHDWSRSXODWLRQ,77ZKLFKLQFOXGH DOOVXEMHFWVZKRKDYHEHHQUDQGRPLVHG
DQG UHFHLYHG DW OHDVW RQH SUHVFULSWLRQ RI VWXG\ PHGLFDWLRQ HJ ))9, RU XVXDO
,&6/$%$LQKDODWLRQSRZGHUIRUDVWKPDPDLQWHQDQFHWKHUDS\

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
58
(DFKVXEMHFWZLOOFRPSOHWHWKH$&7DW9LVLW5DQGRPLVDWLRQ:HHN 9LVLWDQG
:HHN9LVLW$&7VFRUHVZLOODOVREHDVVHVVHGDW:HHN9LVLWDQGDW:HHN
9LVLWDQGDWWKHZLWKGUDZDOWLPHLIDQ\

3ULPDU\$QDO\VHV
7KHSULPDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7WRWDO
VFRUHDVVHVVHGDW:HHN 9LVLW
7KHSULPDU\VHWRIDQDO\VLVLVWKH,77VHW
,IWUHDWPHQWLVZLWKGUDZQWKHQWKHPLVVLQJ$&7VFRUHDWWKHQHDUHVWYLVLWDIWHUWUHDWPHQW
ZLWKGUDZDOZLOOEHUHSODFHGE\WKH$&7VFRUHDVVHVVHGDWZLWKGUDZDOWLPH,IQR$&7
VFRUHLVDVVHVVHGDWZLWKGUDZDOWLPHWKHQWKH$&7PLVVLQJVFRUHDWWKHQHDUHVWYLVLWDIWHU
WUHDWPHQWZLWKGUDZDOZLOOQRWEHUHSODFHG
 1RQLQIHULRULW\WHVWLQJ
7KH QRQLQIHULRULW\ RI ))9, YHUVXV DQ\ RWKHU ,&6/$%$ '3, FRPSDUDWRU ZLOO EH
SULPDULO\WHVWHGLQDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFK7KHPRGHOZLOO
LQFOXGH IDFWRUVDQGFRYDULDWHV DVIROORZ WUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN
DQG :HHN  EDVHOLQH $&7 WUHDWPHQW E\ YLVLW LQWHUDFWLRQ EDVHOLQH $&7 E\ YLVLW
LQWHUDFWLRQ JHQGHU DJH DQG SDWLHQW ZLOO EH ILWWHG DV D UDQGRP IDFWRU 7KH 5HVWULFWHG
0D[LPXP /LNHOLKRRG 5(0/ HVWLPDWLRQ DSSURDFK ZLOO EH XVHG DQG WKH GHIDXOW
FRYDULDQFH VWUXFWXUH ZLOO EH XQVWUXFWXUHG  &RQVLVWHQW ZLWK 0050 PRGHO ILWWLQJ QR
H[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUDJLYHQWLPHSRLQWZLOOEHSHUIRUPHG7KH
FRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRUZLOO
EHHVWLPDWHGDW:HHN9LVLWLQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHGLIWKH
QRQLQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQ
WKHGLIIHUHQFHEHWZHHQ))9,DQGDQ\RWKHUFRPSDUDWRUSRVLWLYHYDOXHVRIWKHGLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\DQDO\VHV
D +DQGOLQJPLVVLQJGDWD
:KLOHVXEMHFWVPLVVLQJ:HHN9LVLWGDWDEXWKDYLQJHDUOLHUGDWDZLOOEHLQFOXGHGLQ
WKH0050SULPDU\DQDO\VLVWKHLQWHUSUHWDELOLW\RIWKHUHVXOWVIURPWKHSULPDU\PRGHO
ZLOOGHSHQGRQWKHPLVVLQJGDWDVDWLVI\LQJWKH0LVVLQJDW5DQGRP0$57RVXSSRUW
WKHYDOLGLW\RIWKHFRQFOXVLRQVGUDZQIURPWKLVDQDO\VLVVHYHUDOVHQVLWLYLW\DQDO\VHVZLOO
EH SHUIRUPHG WR H[SORUH WKH GURSRXW SDWWHUQ DQG LWV SRVVLEOH LPSDFW RQ WUHDWPHQW
FRPSDULVRQV
 0LVVLQJ YDOXHV DW :HHN  9LVLW  ZLOO EH UHSODFHG E\ WKH SRVW
UDQGRPL]DWLRQODVWDYDLODEOHYDOXHHLWKHUWKHZHHNEDVHG$&7VFRUHRUWKH
$&7 VFRUH DW WUHDWPHQW ZLWKGUDZDO WLPH LI DQ\ LH EDVHG RQ WKH /DVW
2EVHUYDWLRQ&DUULHG)RUZDUGPHWKRG7KHFKDQJHIURPEDVHOLQHLQ$&7DW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
59
:HHN  9LVLW  ZLOO EH DQDO\]HG LQ DQ $1&29$ PRGHO DGMXVWLQJ IRU
WUHDWPHQW DQG EDVHOLQH $&7 VFRUH 7KH WUHDWPHQW HIIHFW ))9, YHUVXV DQ\
RWKHU,&6/$%$FRPSDUDWRUDQGLWVFRUUHVSRQGLQJFRQILGHQFHLQWHUYDO
ZLOOEHHVWLPDWHGLQWKLVPRGHOWRWHVWWKHQRQLQIHULRULW\K\SRWKHVLV
 0XOWLSOHLPSXWDWLRQ0,DQDO\VHVXWLOL]LQJFRYDULDWHVNQRZQWREHSUHGLFWLYH
RIUHVSRQVHVHDVRQDWUDQGRPL]DWLRQREVHUYHGYDOXHRI$&7DW:HHN
REVHUYHGYDOXHRI$&7DW:HHN9LVLW2WKHUFRYDULDWHVPD\EH
FRQVLGHUHGDQGLIVRLWZLOOEHGHWDLOHGLQWKH5$3
6WHS   )RU HDFK WUHDWPHQW JURXS VHSDUDWHO\ PLVVLQJ PHDVXUHPHQWV DUH
LPSXWHG IRU VXEMHFWV ZLWK D EDVHOLQH PHDVXUHPHQW ZKHUH WKHUH DUH PLVVLQJ
REVHUYDWLRQVDWHLWKHU:HHNRU:HHNXVLQJWKHDERYHFRYDULDWHVDQG
UHJUHVVLRQEDVHG LPSXWDWLRQ PHWKRG 7KH 0DUNRY &KDLQ 0RQWH &DUOR
0&0&PHWKRGIRU0,ZLOOEHXVHGDQGWHQVXFKVHWVRILPSXWHGGDWDZLOO
EH FUHDWHGHDFKZLWKWKHREVHUYHGYDOXHVRULPSXWHGYDOXHVIRUVXEMHFWVZLWK
PLVVLQJREVHUYDWLRQV
6WHS  (DFK LPSXWHG GDWD VHW ZLOO EH DQDO\]HG XVLQJ WKH SULPDU\ 0050
PRGHO7KHWUHDWPHQWHIIHFWIURPWKHVHDQDO\VHVZLOOWKHQEHSRROHGXVLQJ
VWDQGDUG0,WKHRU\WRPDNHDQRYHUDOOLQIHUHQFH7KHGLIIHUHQFHLQWKHOHDVW
VTXDUHV PHDQV EHWZHHQ WKH WZR JURXSV DW :HHN  9LVLW  DQG WKH
FRUUHVSRQGLQJFRQILGHQFHLQWHUYDOIRUWKHGLIIHUHQFHZLOOEHSUHVHQWHG
E $ VHQVLWLYLW\ DQDO\VLV EDVHG RQ WKH VHPL SDUDPHWULF +RGJHV/HKPDQQ +/
DSSURDFKZLOOEHSURSRVHGWRDVVHVVWKHUREXVWQHVVRIWKH00500RGHOEDVHG
QRQLQIHULRULW\UHVXOWV7KH+/GLIIHUHQFHEHWZHHQJURXSVZLWKWKHFRUUHVSRQGLQJ
FRQILGHQFHLQWHUYDOZLOOEHSURYLGHG
F 6HQVLWLYLW\ DQDO\VHV IRU KDQGOLQJ WUHDWPHQW ZLWKGUDZDO ZKHQ WUHDWPHQW
ZLWKGUDZDORFFXUVDQDOWHUQDWLYHPHWKRGIRULPSXWLQJWKHPLVVLQJYDOXHDWWKH
QHDUHVWYLVLWDIWHUZLWKGUDZDOWLPHZLOOEHSURSRVHGWKHSULPDU\HQGSRLQWPLVVLQJ
YDOXHZLOOEHHVWLPDWHGE\WKHZRUVW$&7VFRUHREVHUYHGEHWZHHQEDVHOLQHYLVLW
LQFOXGHGDQGZLWKGUDZDOWLPHLQFOXGHG
G 7KH SULPDU\ DQDO\VLV LH EDVHG RQ WKH 0050 DSSURDFK DQG WKH VDPH
VHQVLWLYLW\DQDO\VHVSUHVHQWHGKHUHDERYHZLOOEHSHUIRUPHGLQWKH3HU3URWRFRO
VHW
0RGHODVVXPSWLRQVFKHFNLQJ
D $VVXPSWLRQV XQGHUO\LQJ WKH 0050 UHVS $1&29$ IRU WKH VHQVLWLYLW\ DQDO\VLV
PRGHOUHVLGXDOQRUPDOLW\ OLQHDUUHODWLRQVKLSEHWZHHQUHVSRQVH DQGEDVHOLQH$&7
HWFZLOOEHFKHFNHGZLWKJUDSKLFDOPHWKRGVSORWVRIVWXGHQWL]HGUHVLGXDOVHWF
E %DVHOLQH$&7ZLOOEHFDWHJRUL]HGDFFRUGLQJWKHGLVWULEXWLRQTXDUWLOHVDQGWKHVDPH
0050PRGHOUHVS$1&29$IRUWKHVHQVLWLYLW\DQDO\VLVDGMXVWLQJIRUFDWHJRUL]HG
%DVHOLQH$&7ZLOOEHILWWHGDJDLQ

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
60
F 3RVVLEOHWUHDWPHQWE\FRYDULDWHVEDVHOLQH$&7EDVHOLQH$VWKPDWKHUDS\VHDVRQ DW
UDQGRPLVDWLRQ LQWHUDFWLRQ ZLOO EH LQYHVWLJDWHG 0050 UHVS $1&29$ IRU WKH
VHQVLWLYLW\DQDO\VLVDGMXVWLQJIRUWKHVHDGGLWLRQDOLQWHUDFWLRQWHUPV
G 7KH LQIOXHQFH RI WKH FRYDULDWHV DQG SRWHQWLDO DGGLWLRQDO FRYDULDWHV RQ WKH RXWFRPH
ZLOOEHLQYHVWLJDWHG
 6XSHULRULW\WHVWLQJ
,IQRQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI))9,
WR DQ\ RWKHU FRPSDUDWRU ZLOO EH WHVWHG DW WKH XVXDO  WZRVLGHG QRPLQDO OHYHO RI
VLJQLILFDQFH
7KHVDPHPRGHOVDQGDQDO\VHVPHQWLRQHGDERYH ZLOOEHXVHGWRDVVHVVWKHVXSHULRULW\
K\SRWKHVLV

6HFRQGDU\$QDO\VHV
.H\VHFRQGDU\DQDO\VLV
7KHNH\VHFRQGDU\HQGSRLQWLVGHILQHGDVWKHFKDQJHIURPEDVHOLQH9LVLWLQWKH$&7
WRWDOVFRUHDVVHVVHGDW:HHN9LVLW

1RQLQIHULRULW\WHVWLQJ
,IQRQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGDW:HHN 9LVLWWKHQQRQLQIHULRULW\ZLOO
EH WHVWHG DW :HHN  DW WKH  WZRVLGHG QRPLQDO OHYHO ,I QRQLQIHULRULW\ LV QRW
DFFHSWHGDW:HHN 9LVLWQRQLQIHULRULW\ZLOOQRWEHWHVWHGDW:HHN9LVLWDQG
DVVHVVHGRQDGHVFULSWLYHEDVLVRQO\
0RUHSUHFLVHO\WKHNH\VHFRQGDU\HQGSRLQWDVVHVVHGDW:HHN9LVLWZLOODOVREH
DQDO\]HGXVLQJDPL[HGPRGHOUHSHDWHGPHDVXUHV0050DSSURDFKZKHUHGDWDXSWR
DQG LQFOXGLQJ :HHN  9LVLW  ZLOO EH XVHG LQ WKH PRGHO  7KH PRGHO ZLOO LQFOXGH
IDFWRUVDQGDVFRYDULDWHV DVIROORZ WUHDWPHQWVFKHGXOHGYLVLWWLPHSRLQW:HHN:HHN
:HHNDQG:HHNEDVHOLQH $&7WUHDWPHQWE\YLVLWLQWHUDFWLRQEDVHOLQH$&7
E\ YLVLW LQWHUDFWLRQ JHQGHU DJH DQG SDWLHQW ZLOO EH ILWWHG DV D UDQGRP IDFWRU 7KH
5HVWULFWHG 0D[LPXP /LNHOLKRRG 5(0/ HVWLPDWLRQ DSSURDFK ZLOO EH XVHG DQG WKH
GHIDXOWFRYDULDQFHVWUXFWXUHZLOOEHXQVWUXFWXUHG&RQVLVWHQWZLWK0050PRGHOILWWLQJ
QRH[SOLFLWLPSXWDWLRQRIPLVVLQJDVVHVVPHQWVIRUDJLYHQWLPHSRLQWZLOOEHSHUIRUPHG
7KHFRQILGHQFHLQWHUYDORQWKHWUHDWPHQWHIIHFW))9,YV,&6/$%$FRPSDUDWRU
ZLOOEHHVWLPDWHGDW:HHN LQWKLVPRGHO1RQLQIHULRULW\ZLOOEHDFKLHYHGLIWKHQRQ
LQIHULRULW\PDUJLQRILVORZHUWKDQWKHORZHUERXQGRIWKHFRQILGHQFHLQWHUYDORQWKH
GLIIHUHQFH EHWZHHQ ))9, DQG DQ\ RWKHU FRPSDUDWRU SRVLWLYH YDOXHV RI WKH GLIIHUHQFH
IDYRXU))9,
6HQVLWLYLW\ DQDO\VHV WKH VDPH VHQVLWLYLW\ DQDO\VHV DV WKRVH GHVFULEHG DERYH IRU WKH
SULPDU\HQGSRLQWZLOOEHSHUIRUPHGIRUWKHNH\VHFRQGDU\HIILFDF\HQGSRLQW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
61
0RGHODVVXPSWLRQVFKHFNLQJWKHDQDO\VHVSURSRVHGWRFKHFNPRGHODVVXPSWLRQVIRUWKH
DQDO\VLVRIWKHNH\VHFRQGDU\HIILFDF\HQGSRLQWZLOOEHWKHVDPHDVWKRVHGHVFULEHGDERYH
IRUWKHSULPDU\HQGSRLQW
 6XSHULRULW\WHVWLQJ
,IQRQLQIHULRULW\LVVWDWLVWLFDOO\DFKLHYHGDW:HHN9LVLWWKHQVXSHULRULW\RI))9,
YHUVXVDQ\RWKHUFRPSDUDWRUZLOOEHWHVWHGDWWKHXVXDOWZRVLGHGQRPLQDOOHYHORI
VLJQLILFDQFH
7KHVDPHPRGHOVDQGDQDO\VHVPHQWLRQHGDERYHZLOOEHXVHGWRDVVHVVWKHVXSHULRULW\
K\SRWKHVLV
2WKHUVHFRQGDU\DQDO\VHV
3URSHUXVHRIWKHPHGLFDOGHYLFH
7KHRWKHUNH\VHFRQGDU\HQGSRLQWZLOOEHWKHFRUUHFWXVHRIWKHLQKDOHUGHYLFHDVVHVVHGDW
UDQGRPLVDWLRQ9LVLWDW:HHN9LVLWDQG DW:HHN9LVLW7KHGHYLFHZLOO
EHFRQVLGHUHGDVDGHTXDWHO\XVHGLIWKHSDWLHQWGLGQ¶WPDNHDQ\7\SH$HUURUDOOFULWLFDO
LWHPVFRUUHFWDWWKHFRUUHVSRQGLQJYLVLWVUDQGRPLVDWLRQ>9LVLW@ZHHN>9LVLW@DQG
ZHHN>9LVLW@3URSRUWLRQVRIVXEMHFWVFRUUHFWO\XVLQJWKHGHYLFHZLOOEHHVWLPDWHG
ZLWKLQ HDFK JURXS $ FRUUHVSRQGLQJ  FRQILGHQFH LQWHUYDO RI WKH GLIIHUHQFH LQ
SURSRUWLRQVZLOODOVREHSURYLGHG $GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHG
DQGZLOOEHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGQRFDXVDODVVRFLDWLRQ
ZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV

2WKHU$QDO\VHV
2WKHU$QDO\VHV
7KHDQDO\VLVRIWKHRWKHUHQGSRLQWVGHILQHGLQWKLVVHFWLRQZLOOEHSURYLGHGIRU
H[SORUDWRU\SXUSRVHVRQO\$GGLWLRQDOH[SORUDWRU\DQDO\VHVFRXOGEHSHUIRUPHGDQGZLOO
EHGHWDLOHGLQWKH5$3(YHQLIWHVWVZLOOEHSHUIRUPHGDQGFRQILGHQFHLQWHUYDOVZLOO
EHSURYLGHGQRFDXVDODVVRFLDWLRQZLOOEHLQIHUUHGIURPWKHVHDQDO\VHV

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
62
&KDQJHIURPEDVHOLQHLQSUHGRVHWURXJK)(9
5HVXOWVZLOOEHVXPPDUL]HGIRUHDFKJURXSDQGWKHUHVXOWVRIWKHGLIIHUHQFHEHWZHHQ
JURXSVZLOOEHSUHVHQWHGZLWKWKHFRUUHVSRQGLQJFRQILGHQFHLQWHUYDO DW:HHN
9LVLW
5HVSRQVHWRWUHDWPHQW
!
%LQDU\UHVSRQVHGHILQHGDVDQ$&7VFRUHDWDJLYHQYLVLW25D SRLQWLQFUHDVH
IURPEDVHOLQHLQ$&7FKDQJH
7KHUHVSRQGHUDQDO\VHVZLOOEHFRQGXFWHGXVLQJDORJLVWLFUHJUHVVLRQPRGHODWDJLYHQ
9LVLWRU3KRQH&DOODGMXVWLQJIRUWUHDWPHQWDQGVWUDWLILFDWLRQIDFWRUVEDVHOLQH$&7VFRUH
FDWHJRUL]HG LQWR WZR FODVVHV EDVHOLQH DVWKPD WKHUDS\ DQG SRWHQWLDOO\ VHDVRQ DW
UDQGRPL]DWLRQ 7UHDWPHQW E\ VWUDWLILFDWLRQ IDFWRUV LQWHUDFWLRQ HIIHFWV ZLOO EH IXUWKHU
LQYHVWLJDWHGLQDGGLWLRQDOORJLVWLFPRGHOVDGMXVWLQJIRUWKHVHVSHFLILFHIIHFWV
$GKHUHQFHZLWKVWXG\PHGLFDWLRQ
!
1XPEHU RISHUFHQWDJHRIPHGLFDWLRQVGLVSHQVHGDQGFROOHFWHGGXULQJWKHVWXG\ZLOO
EHWDEXODWHGIRUHDFKYLVLWDQGE\WUHDWPHQWJURXS
!
7KHVFRUHIRU0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$DW'D\
:HHNDQG:HHNZLOOEHGHVFULEHGE\WUHDWPHQWJURXS
6HYHUHDVWKPDH[DFHUEDWLRQV
!
1XPEHURIVXEMHFWVZLWKDWOHDVWRQHVHYHUHH[DFHUEDWLRQQXPEHURIVHYHUHDVWKPD
H[DFHUEDWLRQDQGDQQXDOH[DFHUEDWLRQUDWHRYHUWKHVWXG\SHULRG
$VHYHUHDVWKPDH[DFHUEDWLRQLVGHILQHGDVGHWHULRUDWLRQRIDVWKPDUHTXLULQJWKHXVHRI
V\VWHPLF FRUWLFRVWHURLGV WDEOHWV VXVSHQVLRQ RU LQMHFWLRQ ZLWK RU ZLWKRXW DQWLELRWLFV
SUHVFULEHGRUDQLQSDWLHQWKRVSLWDOLVDWLRQRUHPHUJHQF\GHSDUWPHQWYLVLWGXHWRDVWKPD
WKDWUHTXLUHGV\VWHPLFFRUWLFRVWHURLGVRUDQWLELRWLFV 
7KHQXPEHUDQGSHUFHQWDJHRIVXEMHFWVH[SHULHQFLQJDQDVWKPDH[DFHUEDWLRQGXULQJWKH
VWXG\SHULRGZLOOEHVXPPDUL]HGIRUHDFKWUHDWPHQWJURXS/LVWLQJZLOOEHSURYLGHGWR
LQFOXGHWKHSULPDU\FDXVHVRIWKHH[DFHUEDWLRQ
,IIHDVLEOHLHLIWKHQXPEHURIH[DFHUEDWLRQHYHQWVLVKLJKHQRXJKPHDQDQQXDOUDWHRI
DVWKPD H[DFHUEDWLRQ ZLOO EH DQDO\VHG XVLQJ D JHQHUDOLVHG OLQHDU PRGHO DVVXPLQJ WKH
QHJDWLYH ELQRPLDO GLVWULEXWLRQ ZLWK WKH ORJDULWKP RI WLPH RQ WUHDWPHQW DV DQ RIIVHW
YDULDEOH7KHDGMXVWHGPHDQ UDWHVSHU \HDUWUHDWPHQWUDWLRDQG DVVRFLDWHGSYDOXHDQG
FRQILGHQFHLQWHUYDOZLOOEHSUHVHQWHG
+HDOWK5HODWHG4XDOLW\RI/LIHDQG+HDOWKVWDWXV
!
$QLQFUHDVHIURPEDVHOLQHRILQ$4/4VWRWDOVFRUHDW:HHN9LVLW
!
$QLQFUHDVHIURPEDVHOLQHRILQ$4/4VHQYLURQPHQWDOVWLPXOLGRPDLQVFRUH
DW:HHN9LVLW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
63
!
&KDQJH IURP EDVHOLQH LQ WRWDO VFRUH DQG GRPDLQ VFRUHV RI $4/46 DW :HHN 
9LVLW
!
3HUFHQWDJH RI VXEMHFWV ZKR KDYH DQ LQFUHDVH IURP EDVHOLQH RI   LQ $4/46
,QGLYLGXDOGRPDLQVFRUHVDW:HHN 9LVLW
!
+HDOWKVWDWXVXVLQJWKH(XUR4RO4XHVWLRQQDLUH (4'DW:HHN9LVLW
3DWLHQWV6DWLVIDFWLRQDQG3UHIHUHQFHZLWKWKHLQKDOHU3$6$34XHVWLRQQDLUHVHH
$SSHQGL[
7KHRYHUDOOLQKDOHUVDWLVIDFWLRQDQGSUHIHUHQFHZLOOEHPHDVXUHGDW:HHN9LVLW
7KH3$6$3VFRUH ZLOOEHGHVFULEHG VXPPDULVHGE\WUHDWPHQWJURXS
)XUWKHUDQDO\VHVZLOOEHVSHFLILHGLQWKH5HSRUW$QDO\VLV3ODQ
6XEJURXS $QDO\VHV
6XEJURXS VXPPDULHV DQGRU DQDO\VHV ZLOO DOVR EH SURYLGHG ZKHQ DSSURSULDWH IRU
HIILFDF\DQGVDIHW\HQGSRLQWVEDVHGRQEDVHOLQHGLVHDVHFKDUDFWHULVWLFV
$GGLWLRQDO DQDO\VHV FRXOG EH FDUULHG RXW XVLQJ DSSURSULDWH PHWKRGV WR DFFRXQW IRU
FKDQJHVLQWUHDWPHQWGXULQJWKHFRXUVHRIWKHVWXG\)XUWKHUGHWDLOVZLOOEHSURYLGHGLQ
WKHDQDO\VLVSODQ
7KHGHWDLOVZLOOEHSURYLGHGLQWKH5$3
6DIHW\$QDO\VHV
6DIHW\ GDWD ZLOO EH VXPPDUL]HG DQGRU OLVWHG E\ WUHDWPHQW JURXS DQG E\ YLVLW IRU WKH
6DIHW\SRSXODWLRQ
([WHQWRI([SRVXUH
([WHQWRIH[SRVXUHWRVWXG\WUHDWPHQWLHQXPEHURIGD\VRQUDQGRPLVHGWUHDWPHQWZLOO
EHVXPPDULVHGE\WUHDWPHQWJURXSXVLQJPHDQVWDQGDUGGHYLDWLRQPHGLDQPLQLPXP
DQGPD[LPXP,QDGGLWLRQGXUDWLRQRIVXEMHFWH[SRVHGWRVWXG\GUXJZLOOEH VXPPDULVHG
DFURVVWUHDWPHQWJURXSV
$GYHUVH'UXJ5HDFWLRQV
$GYHUVHGUXJUHDFWLRQVGXULQJWKHWUHDWPHQWSHULRGDQGGXULQJWKHSRVWWUHDWPHQWSHULRG
ZLOOEHVXPPDULVHGDQGGLVSOD\HGE\WUHDWPHQWJURXS$GYHUVHGUXJUHDFWLRQVGXULQJWKH
WUHDWPHQW SHULRG LQFOXGH WKRVH ZLWK D GDWH RI RQVHW RQ WKH GDWH RI VWXG\ WUHDWPHQW
LQLWLDWLRQWRRQHGD\DIWHUVWXG\WUHDWPHQWWHUPLQDWLRQ
7KHDGYHUVHGUXJUHDFWLRQVZLOOEHFRGHGXVLQJWKH0HGLFDO'LFWLRQDU\IRU5HJXODWRU\
$FWLYLWLHV0HG'5$DQGZLOOEHUHSRUWHGXVLQJWKHSULPDU\6\VWHP2UJDQ&ODVV62&

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
64
DQG3UHIHUUHG7HUP3UHIHUUHG7HUPVZLOOEHVXPPDULVHGZLWKLQWKHSULPDU\62&7KH
UHODWLRQVKLSRISULPDU\62&SUHIHUUHGWHUPVDQGYHUEDWLPWH[WZLOOEHOLVWHG
7KHQXPEHURIVXEMHFWVZLWKRQHRUPRUHHYHQWVRIDQ\W\SHZLOOEHFDOFXODWHG5HVXOWV
ZLOO EH GLVSOD\HG LQ WKH RUGHU RI GHFUHDVLQJ IUHTXHQF\ ERWK DFURVV SULPDU\ 62& DQG
ZLWKLQSULPDU\62&
$GYHUVH GUXJ UHDFWLRQV GXULQJ WKH VWXG\ SHULRG ZLOO DOVR EH OLVWHG 7KH GHPRJUDSKLF
GHWDLOVHJDJHVH[DQGWKHGHWDLOVRQLQGLYLGXDODGYHUVHHYHQWVZLOOEHLQFOXGHGLQ
WKHVHOLVWLQJV/LVWLQJVZLOOEHVRUWHGZLWKLQVXEMHFWE\WKHDGYHUVHGUXJUHDFWLRQGDWHRI
RQVHW
6LPLODUVXPPDULHVDQGOLVWLQJVZLOOEHSURYLGHGIRUDGYHUVHHYHQWVOHDGLQJWRZLWKGUDZDO
IURPVWXG\
'HDWKVDQG6HULRXV$GYHUVH(YHQWV
'HDWKVDQGVHULRXVDGYHUVHHYHQWVGXULQJWKHVWXG\SHULRGZLOOEHOLVWHG6HULRXVDGYHUVH
HYHQWVGXULQJWKHVWXG\SHULRGZLOO DOVREHVXPPDULVHGE\WUHDWPHQWJURXS
$Q\SUHJQDQFLHVVHULRXVDGYHUVHHYHQWVDQGGHDWKVUHSRUWHGGXULQJWKLVVWXG\ZLOODOVR
EHVXPPDULVHGLQFDVHQDUUDWLYHVZULWWHQE\*6.*&63SHUVRQQHO
2WKHUVDIHW\SDUDPHWHUV
$OORWKHUVVDIHW\SDUDPHWHUVZLOOEHOLVWHGDQGVXPPDUL]HG
0RUHVSHFLILFDOO\WKHYLWDOVLJQV%0,SXOVHUDWHV\VWROLFEORRGSUHVVXUHDQGGLDVWROLF
EORRGSUHVVXUHZLOOEHVXPPDUL]HGE\YLVLWDQGWUHDWPHQWJURXS
*HQHWLFUHVHDUFK
,QIRUPDWLRQUHJDUGLQJJHQHWLFUHVHDUFKLVLQFOXGHGLQ$SSHQGL[

678'<*29(51$1&(&216,'(5$7,216

3RVWLQJRI,QIRUPDWLRQRQ3XEOLFO\$YDLODEOH&OLQLFDO7ULDO
5HJLVWHUV
6WXG\LQIRUPDWLRQIURPWKLVSURWRFROZLOOEHSRVWHGRQSXEOLFO\DYDLODEOHFOLQLFDOWULDO
UHJLVWHUVEHIRUHHQUROPHQWRIVXEMHFWVEHJLQV

5HJXODWRU\DQG(WKLFDO&RQVLGHUDWLRQV,QFOXGLQJWKH
,QIRUPHG&RQVHQW3URFHVV
3ULRUWRLQLWLDWLRQRIDVWXG\VLWH*6.ZLOOREWDLQIDYRXUDEOHRSLQLRQDSSURYDOIURPWKH
DSSURSULDWHUHJXODWRU\DJHQF\WRFRQGXFWWKHVWXG\LQDFFRUGDQFHZLWK,&+*RRG&OLQLFDO
3UDFWLFH*&3DQGDSSOLFDEOHFRXQWU\VSHFLILFUHJXODWRU\UHTXLUHPHQWV

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
65
7KHVWXG\ZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWKDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV
7KHVWXG\ZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWK,&+*&3DOODSSOLFDEOHVXEMHFWSULYDF\
UHTXLUHPHQWVDQGWKHHWKLFDOSULQFLSOHVWKDWDUHRXWOLQHGLQWKH'HFODUDWLRQRI+HOVLQNL
LQFOXGLQJEXWQRWOLPLWHGWR
!
,QVWLWXWLRQDO5HYLHZ%RDUG,5%,QGHSHQGHQW(WKLFV&RPPLWWHH,(&UHYLHZ
&33 LQ )UDQFH ³&RPLWp GH 3URWHFWLRQ GHV 3HUVRQQHV´ DQG IDYRXUDEOH
RSLQLRQDSSURYDORIVWXG\SURWRFRODQGDQ\VXEVHTXHQWDPHQGPHQWV
!
6XEMHFWLQIRUPHGFRQVHQW
!
,QYHVWLJDWRUUHSRUWLQJUHTXLUHPHQWV
*6.ZLOOSURYLGHIXOOGHWDLOVRIWKHDERYHSURFHGXUHVHLWKHUYHUEDOO\LQZULWLQJRUERWK
:ULWWHQLQIRUPHGFRQVHQWPXVWEHREWDLQHGIURPHDFKVXEMHFWSULRUWRSDUWLFLSDWLRQLQWKH
VWXG\

4XDOLW\&RQWURO6WXG\0RQLWRULQJ
,Q DFFRUGDQFH ZLWK DSSOLFDEOH UHJXODWLRQV *&3 DQG *6. SURFHGXUHV *6. PRQLWRUV
ZLOOFRQWDFWWKHVLWHSULRUWRWKHVWDUWRIWKHVWXG\WRUHYLHZZLWKWKHVLWHVWDIIWKHSURWRFRO
VWXG\ UHTXLUHPHQWV DQG WKHLU UHVSRQVLELOLWLHV WR VDWLVI\ UHJXODWRU\ HWKLFDO DQG *6.
UHTXLUHPHQWV:KHQUHYLHZLQJ GDWDFROOHFWLRQSURFHGXUHV WKHGLVFXVVLRQ ZLOOLQFOXGH
LGHQWLILFDWLRQDJUHHPHQWDQGGRFXPHQWDWLRQRIGDWDLWHPVIRUZKLFKPHGLFDOUHFRUGVZLOO
VHUYHDVWKHVRXUFHGRFXPHQW
*6.ZLOOPRQLWRUWKHVWXG\WRHQVXUHWKDWWKH
!
'DWDDUHDXWKHQWLFDFFXUDWHDQGFRPSOHWH
!
6DIHW\DQGULJKWVRIVXEMHFWVDUHEHLQJSURWHFWHG
!
6WXG\LVFRQGXFWHGLQDFFRUGDQFHZLWKWKHFXUUHQWO\DSSURYHGSURWRFRODQGDQ\
RWKHUVWXG\DJUHHPHQWV*&3DQGDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV
7KH ,QYHVWLJDWRU DQG WKH KHDG RI WKH PHGLFDO LQVWLWXWLRQ ZKHUH DSSOLFDEOH DJUHHV WR
DOORZWKHPRQLWRUGLUHFWDFFHVVWRDOOUHOHYDQWGRFXPHQWV

4XDOLW\$VVXUDQFH
7RHQVXUHFRPSOLDQFHZLWK*&3DQGDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV*6.PD\
FRQGXFWDTXDOLW\DVVXUDQFHDVVHVVPHQWDQGRUDXGLWRIWKHVLWHUHFRUGVDQGWKHUHJXODWRU\
DJHQFLHVPD\FRQGXFWDUHJXODWRU\LQVSHFWLRQDWDQ\WLPHGXULQJRUDIWHUFRPSOHWLRQRI
WKH VWXG\ ,Q WKH HYHQW RI DQ DVVHVVPHQW DXGLW RU LQVSHFWLRQ WKH LQYHVWLJDWRU DQG
LQVWLWXWLRQPXVWDJUHHWRJUDQWWKHDGYLVRUVDXGLWRUVDQGLQVSHFWRUVGLUHFWDFFHVVWR
DOOUHOHYDQWGRFXPHQWVDQGWRDOORFDWHWKHLUWLPHDQGWKHWLPHRIWKHLUVWDIIWRGLVFXVVWKH
FRQGXFWRIWKHVWXG\DQ\ILQGLQJVUHOHYDQWLVVXHVDQGWRLPSOHPHQWDQ\FRUUHFWLYHDQGRU
SUHYHQWDWLYHDFWLRQVWRDGGUHVVDQ\ILQGLQJVLVVXHVLGHQWLILHG

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
66

6WXG\DQG6LWH&ORVXUH
8SRQFRPSOHWLRQRUWHUPLQDWLRQRIWKHVWXG\WKH*6.PRQLWRUZLOOFRQGXFWVLWHFORVXUH
DFWLYLWLHVZLWKWKH,QYHVWLJDWRURUVLWHVWDIIDVDSSURSULDWHLQDFFRUGDQFHZLWKDSSOLFDEOH
UHJXODWLRQV*&3DQG*6.6WDQGDUG2SHUDWLQJ3URFHGXUHV
*6. UHVHUYHV WKH ULJKW WR WHPSRUDULO\ VXVSHQG RU WHUPLQDWH WKH VWXG\ DW DQ\ WLPH IRU
UHDVRQV LQFOXGLQJ EXW QRW OLPLWHG WR VDIHW\ LVVXHV HWKLFDO LVVXHV RU VHYHUH QRQ
FRPSOLDQFH,I*6.GHWHUPLQHVWKDWVXFKDFWLRQLVUHTXLUHG*6. ZLOOGLVFXVVWKHUHDVRQV
IRU WDNLQJ VXFK DFWLRQ ZLWK WKH LQYHVWLJDWRU RU KHDG RI WKH PHGLFDO LQVWLWXWLRQ ZKHUH
DSSOLFDEOH:KHQIHDVLEOH*6.ZLOOSURYLGHDGYDQFHQRWLFHWRWKH,QYHVWLJDWRURUKHDG
RIWKHPHGLFDOLQVWLWXWLRQRIWKHLPSHQGLQJDFWLRQ
,IDVWXG\LVVXVSHQGHGRUWHUPLQDWHGIRUVDIHW\UHDVRQV*6.ZLOOSURPSWO\LQIRUPDOO
,QYHVWLJDWRUV KHDGV RI WKH PHGLFDO LQVWLWXWLRQV ZKHUH DSSOLFDEOH DQGRU LQVWLWXWLRQV
FRQGXFWLQJWKHVWXG\*6.ZLOODOVRSURPSWO\LQIRUPWKHUHOHYDQWUHJXODWRU\DXWKRULWLHV
RIWKHVXVSHQVLRQWHUPLQDWLRQDORQJZLWKWKHUHDVRQVIRUVXFKDFWLRQ:KHUHUHTXLUHGE\
DSSOLFDEOHUHJXODWLRQVWKH,QYHVWLJDWRURUKHDGRIWKHPHGLFDOLQVWLWXWLRQPXVWLQIRUPWKH
,(&SURPSWO\DQGSURYLGHWKHUHDVRQVIRUWKHVXVSHQVLRQWHUPLQDWLRQ

5HFRUGV5HWHQWLRQ
)ROORZLQJFORVXUHRIWKHVWXG\WKH,QYHVWLJDWRURUKHDGRIWKHPHGLFDOLQVWLWXWLRQZKHUH
DSSOLFDEOH PXVW PDLQWDLQ DOO VLWH VWXG\ UHFRUGV H[FHSW IRU WKRVH UHTXLUHG E\ ORFDO
UHJXODWLRQVWREHPDLQWDLQHGHOVHZKHUHLQDVDIHDQGVHFXUHORFDWLRQ7KHUHFRUGVPXVW
EHHDVLO\DFFHVVLEOHZKHQ QHHGHG HJIRU D*6. DXGLWRU UHJXODWRU\ LQVSHFWLRQDQG
PXVWEHDYDLODEOHIRUUHYLHZLQFRQMXQFWLRQZLWKDVVHVVPHQWRIWKHIDFLOLW\VXSSRUWLQJ
V\VWHPVDQGUHOHYDQWVLWHVWDII
:KHUH SHUPLWWHG E\ ORFDO ODZVUHJXODWLRQV RU LQVWLWXWLRQDO SROLF\ VRPH RU DOO RI WKH
UHFRUGVPD\EHPDLQWDLQHGLQDIRUPDWRWKHUWKDQKDUGFRS\HJPLFURILFKHVFDQQHG
HOHFWURQLF KRZHYHU FDXWLRQ PXVW EH H[HUFLVHG EHIRUH VXFK DFWLRQ LV WDNHQ 7KH
,QYHVWLJDWRU PXVW HQVXUH WKDW DOO UHSURGXFWLRQV DUH OHJLEOH DQG DUH D WUXH DQG DFFXUDWH
FRS\ RI WKH RULJLQDO ,Q DGGLWLRQ WKH\ PXVW PHHW DFFHVVLELOLW\ DQG UHWULHYDO VWDQGDUGV
LQFOXGLQJUHJHQHUDWLRQRIDKDUGFRS\LIUHTXLUHG7KH,QYHVWLJDWRUDQG*6.PXVWDOVR
HQVXUH WKDW DQ DFFHSWDEOH EDFNXS RI WKH UHSURGXFWLRQV H[LVWV DQG WKDW WKHUH LV DQ
DFFHSWDEOHTXDOLW\FRQWUROSURFHGXUHLQSODFHIRUFUHDWLQJWKHUHSURGXFWLRQV
*6.ZLOOLQIRUPWKH,QYHVWLJDWRURIWKHWLPHSHULRGIRUUHWDLQLQJWKHVLWHUHFRUGVLQRUGHU
WRFRPSO\ZLWKDOO DSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV7KHPLQLPXPUHWHQWLRQWLPHZLOO
PHHW WKH VWULFWHVW VWDQGDUG DSSOLFDEOH WR D SDUWLFXODU VLWH DV GLFWDWHG E\ ORFDO
ODZVUHJXODWLRQV*6.VWDQGDUGRSHUDWLQJSURFHGXUHVDQGRULQVWLWXWLRQDOUHTXLUHPHQWV
7KH *3,QYHVWLJDWRU PXVW QRWLI\ *6. RI DQ\ FKDQJHV LQ WKH DUFKLYDO DUUDQJHPHQWV
LQFOXGLQJ EXW QRW OLPLWHG WR DUFKLYDO RI UHFRUGV DW DQ RIIVLWH IDFLOLW\ RU WUDQVIHU RI
RZQHUVKLSRIWKHUHFRUGVLQWKHHYHQWWKDWWKH,QYHVWLJDWRULVQRORQJHUDVVRFLDWHGZLWKWKH
VLWH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
67

3URYLVLRQRI6WXG\5HVXOWVWR,QYHVWLJDWRUV3RVWLQJRI
,QIRUPDWLRQRQ3XEOLFDOO\$YDLODEOH&OLQLFDO7ULDOV5HJLVWHUV
DQG3XEOLFDWLRQ
:KHUHUHTXLUHGE\DSSOLFDEOHUHJXODWRU\UHTXLUHPHQWVDQ,QYHVWLJDWRUVLJQDWRU\ZLOOEH
LGHQWLILHGIRUWKHDSSURYDORIWKHFOLQLFDOVWXG\UHSRUW7KH,QYHVWLJDWRUVLJQDWRU\ZLOOEH
SURYLGHGUHDVRQDEOHDFFHVVWRVWDWLVWLFDOWDEOHVILJXUHVDQGUHOHYDQWUHSRUWVDQGZLOOKDYH
WKHRSSRUWXQLW\ WR UHYLHZ WKHFRPSOHWH VWXG\ UHVXOWV DWD*6. VLWH RU RWKHU PXWXDOO\
DJUHHDEOHORFDWLRQ
*6.ZLOODOVRSURYLGHWKH,QYHVWLJDWRUZLWKWKHIXOOVXPPDU\RIWKHVWXG\UHVXOWV7KH
,QYHVWLJDWRU LV HQFRXUDJHG WR VKDUH WKH VXPPDU\ UHVXOWV ZLWK WKH VWXG\ VXEMHFWV DV
DSSURSULDWH
*6. DLPV WR SRVW D UHVXOWV VXPPDU\ WR WKH *6. &OLQLFDO 6WXG\ 5HJLVWHU DQG RWKHU
SXEOLFO\DYDLODEOHUHJLVWHUVQRODWHUWKDQPRQWKVDIWHUWKHODVWVXEMHFW¶VODVWYLVLW/6/9
>WKLVDSSOLHVWRHDFKGDWDDQDO\VLVSKDVHIRUVWXGLHVZLWKPXOWLSOHSKDVHVHJSULPDU\
DQDO\VLVIROORZXSDQDO\VLVHWF@,QDGGLWLRQWKHDLPLVWRVXEPLWDPDQXVFULSWWRDSHHU
UHYLHZHGMRXUQDOIRUSXEOLFDWLRQZLWKLQPRQWKVRI/6/9*6.DOVRDLPVWRSXEOLVK
WKHIXOOVWXG\SURWRFRORQWKH*6.&OLQLFDO6WXG\5HJLVWHUDWWKHWLPHWKHUHVXOWVRIWKH
VWXG\DUHSXEOLVKHGDVDPDQXVFULSWLQWKHVFLHQWLILFOLWHUDWXUH
:KHQ PDQXVFULSW SXEOLFDWLRQ LQ D SHHUUHYLHZHG MRXUQDO LV QRW IHDVLEOH IXUWKHU VWXG\
LQIRUPDWLRQZLOOEHSRVWHGWRWKH*6.&OLQLFDO6WXG\5HJLVWHUWRVXSSOHPHQWWKHUHVXOWV
VXPPDU\
$PDQXVFULSWZLOOEHSURJUHVVHGIRUSXEOLFDWLRQLQWKHVFLHQWLILFOLWHUDWXUHLIWKHUHVXOWV
SURYLGHLPSRUWDQWVFLHQWLILFRUPHGLFDONQRZOHGJH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
68

5()(5(1&(6
%ULWLVK*XLGHOLQHRQWKH0DQDJHPHQWRI$VWKPD%ULWLVK7KRUDFLF6RFLHW\$QDWLRQDO
FOLQLFDOJXLGHOLQHLYLY
&RKHQ -/0DQQ'0:LVQLYHVN\-3+RUQH5/HYHQWKDO+0XVXPHFL6]DER7-+DOP
($ $VVHVVLQJ WKH YDOLGLW\ RI VHOIUHSRUWHG PHGLFDWLRQ DGKHUHQFH DPRQJ LQQHUFLW\
DVWKPDWLF DGXOWV WKH 0HGLFDWLRQ $GKHUHQFH 5HSRUW 6FDOH IRU $VWKPD $QQ $OOHUJ\
$VWKPD,PPXQRO
'RODQ30RGHOLQJYDOXDWLRQVIRU(XUR4ROKHDOWKVWDWHV0HG&DUH

)DQWD&+'UXJ7KHUDS\$VWKPD1HZ(QJO-0HG
*,1$KWWSZZZJLQDVWKPDRUJORFDOXSORDGVILOHV*,1$B5HSRUWB0DUFKSGI
*OD[R6PLWK.OLQH'RFXPHQW1XPEHU 50)OXWLFDVRQH)XURDWH
9LODQWHURO,QYHVWLJDWRU
V%URFKXUH-XQ
*OREDO ,QLWLDWLYH IRU $VWKPD *,1$ *OREDO 6WUDWHJ\ IRU $VWKPD 0DQDJHPHQW DQG
3UHYHQWLRQ*,1$ZZZJLQDVWKPDRUJ
+DWFKHU5$7UXVVHOO-1HOVRQ$/&DWHV:-U6WHZDUW).RZDO'HGLWRUV
&RQWUDFHSWLYH7HFKQRORJ\WKHGLWLRQ1HZ<RUN$UGHQW0HGLDD7DEOH

+DWFKHU 5$ 7UXVVHOO - 1HOVRQ $/ &DWHV : -U 6WHZDUW ) .RZDO ' HGLWRUV
&RQWUDFHSWLYH7HFKQRORJ\WKHGLWLRQ1HZ<RUN$UGHQW0HGLDE
-DPHV/3HWDO3KDUPDFRNLQHWLFVRI$FHWDPLQRSKHQ3URWHLQ$GGXFWVLQ$GXOWVZLWK
$FHWDPLQRSKHQ2YHUGRVHDQG$FXWH/LYHU)DLOXUH'UXJ0HWDE'LVSRV

-XQLSHU()HWDO'HWHUPLQLQJDPLQLPDOLPSRUWDQWFKDQJHLQDGLVHDVHVSHFLILF4XDOLW\RI
/LIH4XHVWLRQQDLUH-&OLQ(SLGHPLRO-DQ
-XQLSHU()HWDO(YDOXDWLRQRILPSDLUPHQWRIKHDOWKUHODWHGTXDOLW\RIOLIHLQDVWKPD
GHYHORSPHQWRIDTXHVWLRQQDLUHIRUXVHLQFOLQLFDOWULDOV7KRUD[)HE
-XQLSHU()*X\DWW*+:LOOLDPV$*ULIILWK/(0HDVXULQJTXDOLW\RIOLIHLQDVWKPD$P
5HY5HVSLU'LV
-XQLSHU()$VWKPDTXDOLW\RIOLIHTXHVWLRQQDLUHV$4/4$4/46DQG0LQL$4/4
%DFNJURXQGLQIRUPDWLRQ DQGLQWHUYLHZLQJWLSV42/7HFKQRORJLHV,QF
.R]PD&0HWDO'HYHORSPHQWDQG9DOLGDWLRQRID3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH
4XHVWLRQQDLUHIRU,QKDODWLRQ'HYLFHV3$6$347UHDW5HVSLU0HG

2017N339371_00

2014N190259_00 
&21),'(17,$/
 
 
 
HZA116492 
 
69 
 
/H*DO)HWDO4XDQWLILFDWLRQRI+HSDWLWLV'HOWD9LUXV51$LQ6HUXPE\&RQVHQVXV
5HDO7LPH3&5,QGLFDWHV'LIIHUHQW3DWWHUQVRI9LURORJLFDO5HVSRQVHWR,QWHUIHURQ
7KHUDS\LQ&KURQLFDOO\,QIHFWHG3DWLHQWV-&OLQ0LFURELRO±
1DWKDQ5$6RUNQHVV&$.RVLQVNL0HWDO'HYHORSPHQWRIWKH$VWKPD&RQWURO7HVW$
VXUYH\IRUDVVHVVLQJDVWKPDFRQWURO-$OOHUJ\&OLQ,PPXQRO-DQXDU\

1,+$VWKPD*XLGHOLQHV6XPPDU\
KWWSZZZQKOELQLKJRYJXLGHOLQHVDVWKPDDVWKVXPPSGI

3HGHUVHQ62
%\UQH3$FRPSDULVRQRIHIILFDF\DQGVDIHW\RILQKDOHGFRUWLFRVWHURLGVLQ
DVWKPD$OOHUJ\

6FKDW] 0 HW DO 7KH PLQLPDOO\ LPSRUWDQW GLIIHUHQFH RI WKH $VWKPD &RQWURO 7HVW 7KH
-RXUQDORIDOOHUJ\DQGFOLQLFDOLPPXQRORJ\
7KH (XUR4RO *URXS   7KH (XUR4RO *URXS (XUR4RO D QHZ IDFLOLW\ IRU WKH
PHDVXUHPHQWRIKHDOWKUHODWHGTXDOLW\RIOLIH+HDOWK3ROLF\
(4'/ XVHU JXLGH %DVLF LQIRUPDWLRQ RQ KRZ WR XVH WKH (4'/ LQVWUXPHQW
9HUVLRQ2FWREHU0DQG\2HUPDQ%DV-DQVVHQ
:+2&215$'7HFKQLFDO&RQVXOWDWLRQRQQRQR[\QRO:+2*HQHYD±2FWREHU
6XPPDU\UHSRUW*HQHYD:RUOG+HDOWK2UJDQL]DWLRQ


2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
70

$33(1',&(6

$SSHQGL[$EEUHYLDWLRQDQG7UDGHPDUNV
$&7
$VWKPD&RQWURO7HVW
$'5
$GYHUVH'UXJ5HDFWLRQ
$(
$GYHUVH(YHQW
$/7
$ODQLQH$PLQRWUDQVIHUDVH
$1&29$
$4/46
$QDO\VLVRI&RYDULDQFH
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH
$67
$VSDUWDWH$PLQRWUDQVIHUDVH
%,'
%8'
&
7ZLFHGDLO\
%XGHVRQLGH
&HOVLXV
&5)
&DVH5HFRUG)RUP
H&5)
(OHFWURQLF&DVH5HFRUG)RUP
&9
&DUGLRYDVFXODU
'3,
'U\3RZGHU,QKDOHU
)3
)OXWLFDVRQH3URSLRQDWH
(3,
(SLGHPLRORJ\
(4'
)
(XUR4RO'
)RUPRWHURO
)'$
)(9
)RRGDQG'UXJ$GPLQLVWUDWLRQ
)RUFHGH[SLUDWRU\YROXPHLQRQHVHFRQG
))
)3
)OXWLFDVRQH)XURDWH
)OXWLFDVRQH3URSLRQDWH
)6+
)ROOLFOH6WLPXODWLQJ+RUPRQH
*&3
*RRG&OLQLFDO3UDFWLFH
*&63
*OREDO&OLQLFDO6DIHW\DQG3KDUPDFRYLJLODQFH
*3
*HQHUDO3UDFWLWLRQHU
*6.
*OD[R6PLWK.OLQH
,%
,QYHVWLJDWRUV%URFKXUH
,&6
,QKDOHG&RUWLFRVWHURLG
,(&
,QGHSHQGHQW(WKLFV&RPPLWWHH
,J0
,PPXQRJOREXOLQ0
,15
,QWHUQDWLRQDO1RUPDOLVHG5DWLR
,3
,QYHVWLJDWLRQDO3URGXFW
,5%
,QVWLWXWLRQDO5HYLHZ%RDUG
,77
,QWHQWWR7UHDW
,9'
,Q9LWUR'LDJQRVWLF
,57
,QWHUDFWLYH5HVSRQVH7HFKQRORJ\
/$%$
/RQJ$FWLQJ%HWD$JRQLVW
/'+
/DFWDWH'HK\GURJHQDVH
/6/9
0$56$
/DVW6XEMHFW/DVW9LVLW
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHLQ$VWKPD
TXHVWLRQQDLUH
0HG'5$
0FJ
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV
0LFURJUDP

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
71
0,'
0LQLPDOO\,PSRUWDQW'LIIHUHQFH
0',
0HWHUHG'RVH,QKDOHU
0&,'
0LQLPDOO\&OLQLFDOO\,PSRUWDQW'LIIHUHQFH
PO
0LOOLOLWUH
06'6
0DWHULDO6DIHW\'DWD6KHHW
0050
0L[HGHIIHFWVPRGHOZLWKUHSHDWHGPHDVXUHV
1'3,
1RYHO'U\3RZGHU,QKDOHU
3$6$34
3.
33
352
3DWLHQWV6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH
3KDUPDFRNLQHWLFV
3HUSURWRFRO
3DWLHQW5HSRUWHG2XWFRPHV
SJ
3LFRJUDP
SPRO
3LFRPROHV
4'
2QFH'DLO\
4R/
4XDOLW\RI/LIH
47F
&RUUHFWHG47LQWHUYDO
5$3
5HSRUWLQJ$QDO\VLV3ODQ
5(0/
51$
5HVWULFWHGPD[LPXPOLNHOLKRRG
5LERQXFOHLF$FLG
6
6$(
6DOPHWHURO
6HULRXV$GYHUVH(YHQW
6$3
6WDWLVWLFDO$QDO\VLV3ODQ
6'
62&
623
6WDQGDUGGHYLDWLRQ
6\VWHPRUJDQFODVV
6WDQGDUG2SHUDWLQJ3URFHGXUH
6	3
6WDWLVWLFVDQG3URJUDPPLQJ
630
6WXG\3URFHGXUHV0DQXDO
8/1
8SSHU/LPLWRI1RUPDO
9,
9LODQWHURO
:+2
:RUOG+HDOWK2UJDQLVDWLRQ
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
',6.86
$&7
(//,37$
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH
$4/46
5(/9$5
(4'
6(5(7,'(
0$56$TXHVWLRQQDLUH
3$6$34XHVWLRQQDLUH
6\PELFRUW7XUEXKDOHU
;2/$,5

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
72

$SSHQGL[
6WXG\6FKHPDWLF
))9,RSHQ ODEHORUXVXDODVWKPDPDLQWHQDQFHWUHDWPHQW
+=$VWXG\ GHVLJQ
9
'D\
5DQGRPLVDWLRQ
9
'D\
6FUHHQLQJ
ACT , MARS-A, 
AQLQ, EQ-5D, 
Spirometry
$VWKPD WUHDWHG ZLWK
,&60','3,Q 
Relvar 92/22 or 184/22 μg
ICS/LABA DPI on the market
Seretide®, Symbicort®
1-7 days
5
PRQWKV
ACT < 20
V2, errors ass-t:
• Read,
•Demonstrationby HCP,
•1 dose,
•Errors asst & correction
9
:HHN 
9
:HHN 
Possibility to combine 
V1+V2= Day 0
9
3KRQHFDOO
:HHN 
9
3KRQHFDOO
:HHN 
V4, errors ass-t:
•1 dose,
•Errors asst
•Demonstration by 
HCP if critical errors
V6, errors ass-t:
•1 dose,
•Errors asst
•Demonstration by 
HCP if critical errors
ACT, safety
ACT, safety
ACT , MARS-A, 
PASAP, 
Spirometry
ACT , MARS-A, 
AQLQ, EQ-5D
$SKRQHFDOOLVSURYLGHGDW:HHNDQG:HHNLQRUGHUWRFKHFNZKHWKHUWKHVXEMHFW
KDVH[SHULHQFHGDQ\DGYHUVHHYHQWVDQGWKHQWKH,QYHVWLJDWRUFDOOLQJWKHSDWLHQWPXVW
GHWHUPLQHZKHWKHUWKHHYHQWLVUHODWHGWRVWXG\PHGLFDWLRQHLWKHUDUPDQGZKHWKHU
WKHHYHQWLVVHULRXV$WWKHVHWHOHSKRQHFDOOVVXEMHFWVZLOODOVREHDVNHGWRFRPSOHWH
WKH$&7TXHVWLRQQDLUHDQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
9LVLW:HHNVKRXOGEHVFKHGXOHGDWWKHVDPHWLPHRIGD\DV9LVLW5DQGRPLVDWLRQ
YLVLW

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
73

$SSHQGL[4XHVWLRQQDLUHV
$VWKPD&RQWURO7HVW$&7
7KH $&7 LV D YDOLGDWHG VHOIDGPLQLVWHUHG TXHVWLRQQDLUH XWLOLVLQJ  TXHVWLRQV WR DVVHVV
DVWKPD FRQWURO GXULQJ WKH SDVW  ZHHNV RQ D SRLQW FDWHJRULFDO VFDOH  WR  %\
DQVZHULQJ DOO  TXHVWLRQV D VXEMHFW ZLWK DVWKPD FDQ REWDLQ D VFRUH WKDW PD\ UDQJH
EHWZHHQDQGZLWKKLJKHUVFRUHVLQGLFDWLQJEHWWHUFRQWURO$Q$&7VFRUHRIWR
VXJJHVWVWKDWWKHVXEMHFW¶VDVWKPDLVXQOLNHO\WREHZHOOFRQWUROOHG$VFRUHRIWR
VXJJHVWV WKDW WKH VXEMHFW¶V DVWKPD LV OLNHO\ WR EH ZHOO FRQWUROOHG 7KH WRWDO VFRUH LV
FDOFXODWHGDVWKHVXPRIWKHVFRUHVIURPDOOTXHVWLRQV>1DWKDQ 5@7KHPLQLPDOO\
LPSRUWDQWGLIIHUHQFH0,'IRU$&7LV>6FKDW]@
6XEMHFWV ZLOO FRPSOHWHWKH$&7 DW6FUHHQLQJ 9LVLWDW5DQGRPLVDWLRQ9LVLW DW
:HHN9LVLWDQG DW:HHN9LVLW RQVLWH7ZRWHOHSKRQHFDOOVDUHSURYLGHGDW
:HHNDQGDQGVXEMHFWVZLOOEHDVNHGWRSURYLGHUHVSRQVHVWRWKH$&7TXHVWLRQQDLUH
DQGWRVHQGLWEDFNWRWKH,QYHVWLJDWRU
7KH $&7 KDV EHHQ GHYHORSHG DV D PHDVXUH RI VXEMHFWV¶ DVWKPD FRQWURO WKDW FDQ EH
TXLFNO\DQGHDVLO\FRPSOHWHGLQFOLQLFDOSUDFWLFH7KHTXHVWLRQVDUHGHVLJQHGWREHVHOI
FRPSOHWHGE\WKHVXEMHFW,WLVUHFRPPHQGHGWKDWWKH$&7EHDGPLQLVWHUHGDWWKHVDPH
WLPH GXULQJ HDFK YLVLW 7KH $&7 VKRXOG EH FRPSOHWHG EHIRUH DQ\ SURFHGXUHV DUH
SHUIRUPHG RQ WKH VXEMHFW WR DYRLG LQIOXHQFLQJ WKH VXEMHFW¶V UHVSRQVH $GHTXDWH WLPH
VKRXOGEHDOORZHGWRFRPSOHWHDOOLWHPVRQWKH$&7
7KHVXEMHFWVKRXOGFRPSOHWHWKHTXHVWLRQQDLUHLQDTXLHWDUHD
7KH ,QYHVWLJDWRU VKRXOG DVN WKH VXEMHFW WR FRPSOHWH WKH TXHVWLRQV DV DFFXUDWHO\ DV
SRVVLEOH,IWKHVXEMHFWUHTXHVWVKHOSRUFODULILFDWLRQZLWKDQ\RIWKHTXHVWLRQVKHVKHZLOO
EHDVNHGWRUHUHDGWKHLQVWUXFWLRQVDQGJLYHWKHDQVZHUWKDWEHVWUHIOHFWVKRZKHVKHIHOW
RYHU WKH SUHYLRXV  ZHHNV 7KH VXEMHFW VKRXOG EH UHDVVXUHG WKDW WKHUH DUH QR ULJKW RU
ZURQJ DQVZHUV 7KH ,QYHVWLJDWRU VKRXOG QRW SURYLGH WKH VXEMHFW ZLWK DQ\ DQVZHU RU
DWWHPSWWRLQWHUSUHWDQ\SRUWLRQRIDTXHVWLRQ
3OHDVHUHIHUWRWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV
$VWKPD4XDOLW\RI/LIH4XHVWLRQQDLUH$4/46
7KH $4/4 6 LV D PRGLILHG YHUVLRQ RI WKH RULJLQDO $4/4 LQ ZKLFK DOO WKH DFWLYLW\
TXHVWLRQVDUHJHQHULFDQGLWKDVEHHQYDOLGDWHGIRUXVHLQDVWKPDVXEMHFWVEHWZHHQWKH
DJHV RI  DQG  7KH $4/4 LV D GLVHDVHVSHFLILF VHOIDGPLQLVWHUHG TXDOLW\ RI OLIH
TXHVWLRQQDLUHGHYHORSHGWRHYDOXDWHWKHLPSDFWRIDVWKPDWUHDWPHQWVRQWKHTXDOLW\RIOLIH
RIDVWKPDVXIIHUHUVRYHUWKHODVWZHHNV>-XQLSHU@$4/46ZLOOEHPHDVXUHGDW
5DQGRPLVDWLRQDQGDW:HHN(DUO\:LWKGUDZDOYLVLW
7KH $4/4 ZKLFK LV DYDLODEOH LQ QXPHURXV ODQJXDJHV KDV D GHPRQVWUDWHG YDOLGLW\
UHOLDELOLW\ DQG UHSURGXFLELOLW\ >-XQLSHU  -XQLSHU @ 7KH $4/4 FRQWDLQV 
LWHPV LQ IRXU GRPDLQV DFWLYLW\ OLPLWDWLRQ  LWHPV V\PSWRPV  LWHPV HPRWLRQDO
IXQFWLRQLWHPVDQGHQYLURQPHQWDOVWLPXOLLWHPV,QDGGLWLRQWKHLWHPVRIWKH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
74
TXHVWLRQQDLUHDUHDOVRDYHUDJHGWRSURGXFHDQRYHUDOOTXDOLW\RIOLIHVFRUH7KHUHVSRQVH
IRUPDWFRQVLVWVRIDVHYHQSRLQWVFDOHZKHUHDYDOXHRILQGLFDWHV³WRWDOLPSDLUPHQW´DQG
 LQGLFDWHV ³QR LPSDLUPHQW´ $VVXPLQJ D VWDWLVWLFDOO\ VLJQLILFDQW UHVXOW S  WKH
PLQLPDOFOLQLFDOO\PHDQLQJIXOFKDQJHLQRYHUDOOTXDOLW\RIOLIHRULQTXDOLW\RIOLIHIRU
DQ\RIWKHLQGLYLGXDOGRPDLQVLVSRLQWV>-XQLSHU@
,WLVUHFRPPHQGHGWKDWWKH$4/46EHDGPLQLVWHUHGDWWKHVDPHWLPHGXULQJHDFKYLVLW
7KH $4/4 6 PXVW EH DGPLQLVWHUHG EHIRUH LQTXLULQJ DERXW $(V DQG DQ\ VWXG\
DVVHVVPHQWV$GHTXDWHWLPHVKRXOGEHDOORZHGWRFRPSOHWHDOOLWHPVRQWKH$4/46
1RVWDWHGRULPSOLHGWLPHIRUFRPSOHWLQJWKH$4/46ZLOOEHJLYHQWKRXJKWKHVXUYH\
W\SLFDOO\WDNHVWRPLQXWHVWRFRPSOHWH
6XEMHFWVVKRXOGFRPSOHWHDOOWKHTXHVWLRQVIURPWKH$4/467KH,QYHVWLJDWRUZLOODVN
WKHVXEMHFWWRFRPSOHWHDOOTXHVWLRQVDVDFFXUDWHO\DVSRVVLEOH,IWKHVXEMHFWUHTXHVWVKHOS
RUFODULILFDWLRQRIDQ\TXHVWLRQLQ WKH$4/46KHRUVKHVKRXOGEHDVNHGWRUHUHDGWKH
LQVWUXFWLRQVDQGJLYHWKHDQVZHUWKDWEHVWUHIOHFWVKRZKHVKHIHHOVRYHUWKHSUHYLRXVWZR
ZHHNV7KHVXEMHFWVKRXOGEHUHDVVXUHGWKDWWKHUHDUHQR ULJKWRUZURQJDQVZHUV7KH
,QYHVWLJDWRU ZLOO QRW SURYLGH WKH VXEMHFW ZLWK DQ\ DQVZHU RU DWWHPSW WR LQWHUSUHW DQ\
SRUWLRQRIDTXHVWLRQ3OHDVHUHIHUWRWKH6WXG\3URFHGXUHV0DQXDOIRUIXUWKHUGHWDLOV
(XUR4RO4XHVWLRQQDLUH(4'/HYHO
*HQHUDOKHDOWKVWDWXVZLOOEHDVVHVVHGZLWKWKH(XUR4RO(4'/HYHO 4XHVWLRQQDLUH
DW5DQGRPLVDWLRQDQG:HHN(DUO\:LWKGUDZDOYLVLW
7KH(4'LVDVWDQGDUGLVHGLQVWUXPHQWIRUXVHDVDPHDVXUHRIKHDOWKVWDWXVWKDWDVNV
VXEMHFWV TXHVWLRQV DERXW WKHLU KHDOWK VWDWXV ³WRGD\´ >7KH (XUR4RO *URXS @ ,W LV
GHVLJQHGIRU VHOIFRPSOHWLRQDQGLV FRJQLWLYHO\VLPSOH7KH(4' LV DWZRSDUWVHOI
DVVHVVPHQWTXHVWLRQQDLUH7KHILUVWSDUWFRQVLVWVRIILYHLWHPVFRYHULQJILYHGLPHQVLRQV
PRELOLW\ VHOI FDUH XVXDO DFWLYLWLHV SDLQGLVFRPIRUW DQG DQ[LHW\GHSUHVVLRQ (DFK
GLPHQVLRQ LV PHDVXUHG E\ D WKUHHSRLQW /LNHUW VFDOH QR SUREOHP VRPHPRGHUDWH
SUREOHPVDQGXQDEOHH[WUHPHSUREOHPV
5HVSRQGHQWVDUHDVNHGWRFKRRVHRQHOHYHOWKDWUHIOHFWVWKHLURZQKHDOWKVWDWHWRGD\IRU
HDFKRIWKHILYHGLPHQVLRQV5HVSRQGHQWVFDQWKHQEHFODVVLILHGLQWRRQHRIGLVWLQFW
KHDOWK VWDWHV (4' KHDOWK VWDWHV FDQ EH FRQYHUWHG WR D VLQJOH VXPPDU\ LQGH[ E\
DSSO\LQJ DIRUPXODWKDWDWWDFKHVZHLJKWVWRHDFKRIWKHOHYHOVLQHDFKGLPHQVLRQ7KH
IRUPXOD LV EDVHG RQ WKH YDOXDWLRQ RI (4' KHDOWK VWDWHV IURP JHQHUDO SRSXODWLRQ
VDPSOHV>'RODQ @
7KHVHFRQGSDUWRIWKHTXHVWLRQQDLUHFRQVLVWVRIDYHUWLFDOYLVXDODQDORJXHVFDOH(4'
9$6 WKDWKDV HQGSRLQWV RI 7KHEHVWKHDOWK \RXFDQLPDJLQHDQFKRUHGDW DQG
7KHZRUVWKHDOWK\RXFDQLPDJLQHDQFKRUHGDW5HVSRQGHQWVDUHDVNHGWRLQGLFDWH
KRZWKH\UDWHWKHLUFXUUHQWKHDOWKVWDWHE\GUDZLQJDOLQHIURPWKHER[PDUNHG³\RXUKHDOWK
VWDWXVWRGD\´WRWKHDSSURSULDWHSRLQWRQWKH(4'9$6VFDOH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
75
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH(4'DWWKHVDPHWLPHDWWKH
VSHFLILHG YLVLWV DQG EHIRUH DQ\ VWXG\ SURFHGXUHV 7KH (4' ZLOO EH DGPLQLVWHUHG DW
5DQGRPLVDWLRQ9LVLWDQG:HHN 9LVLW (DUO\:LWKGUDZDOYLVLW
0HGLFDWLRQ$GKHUHQFH5HSRUW6FDOHIRU$VWKPD0$56$
5HSRUWHGDGKHUHQFHWRPHGLFDWLRQZLOOEHDVVHVVHGZLWKWKH0HGLFDWLRQ$GKHUHQFH5HSRUW
6FDOHIRU$VWKPD0$56$TXHVWLRQQDLUHDW9LVLW9LVLWDQG9LVLW(DUO\:LWKGUDZDO
YLVLW
7KH0$56$LVDLWHPTXHVWLRQQDLUHZKHUHPHGLFDWLRQXVH LVUDWHGRQDSRLQW/LNHUW
VFDOHLQGLFDWLQJµDOZD\V¶WRLQGLFDWLQJµQHYHU¶,WKDVEHHQYDOLGDWHGDVDVHOIUHSRUWHG
PHDVXUHRIDGKHUHQFHZLWK,&6IRUVXEMHFWVZLWKDVWKPDDQGLQFOXGHVJHQHULF³,XVHLW
UHJXODUO\HYHU\GD\´DQGOXQJFRQGLWLRQVSHFLILFTXHVWLRQVDERXWPHGLFDWLRQXVH³,RQO\XVH
LWZKHQ,IHHOEUHDWKOHVV´>&RKHQ@7KHUHLVQRVSHFLILHGWLPHIUDPHRQZKLFK
UHVSRQVHVVKRXOGEHEDVHG
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH0$56$DWWKHVDPHWLPHDWWKH
VSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH0$56KDYHQRVSHFLILHGWLPHIUDPHRQ
ZKLFKUHVSRQVHVVKRXOGEHEDVHG
3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH3$6$34
7KH3DWLHQW6DWLVIDFWLRQDQG3UHIHUHQFH4XHVWLRQQDLUH3$6$34>&0.R]PD @
LV D PXOWLLWHP PHDVXUH RI UHVSLUDWRU\ LQKDODWLRQ GHYLFH VDWLVIDFWLRQ DQG SUHIHUHQFH
GHVLJQHGWREHHDVLO\XQGHUVWRRGDQGDGPLQLVWHUHGWRSDWLHQWVZLWKDVWKPDDQG&23'
3DWLHQWVDWLVIDFWLRQZLWKHDFKGHYLFHDQGGHYLFHSUHIHUHQFHZLOOEHDVVHVVHGDW9LVLW
(DUO\:LWKGUDZDOYLVLW
7KH,QYHVWLJDWRUVKRXOGHQVXUHWKHVXEMHFWFRPSOHWHVWKH3$6$34DWWKHVDPHWLPHDWWKH
VSHFLILHGYLVLWVDQGEHIRUHDQ\VWXG\SURFHGXUHV7KH3$6$34KDVQRVSHFLILHGWLPHIUDPH
RQZKLFKUHVSRQVHVVKRXOGEHEDVHG

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
76

$SSHQGL[ /LYHU&KHPLVWU\6WRSSLQJDQG)ROORZXS
&ULWHULD
3KDVH,,,,9OLYHUFKHPLVWU\VWRSSLQJDQGLQFUHDVHGPRQLWRULQJFULWHULD KDYHEHHQ
GHVLJQHGWRDVVXUHVXEMHFWVDIHW\DQGHYDOXDWHOLYHUHYHQWHWLRORJ\LQDOLJQPHQWZLWKWKH
)'$SUHPDUNHWLQJFOLQLFDOOLYHUVDIHW\JXLGDQFH
KWWSZZZIGDJRYGRZQORDGV'UXJV*XLGDQFH&RPSOLDQFH5HJXODWRU\,QIRUPDWLRQ*XLG
DQFHV8&0SGI
3KDVH,,,,9OLYHUFKHPLVWU\VWRSSLQJFULWHULDDQGUHTXLUHGIROORZXSDVVHVVPHQWV
Liver Chemistry Stopping Criteria - Liver Stopping Event
ALT-absolute
$/7∀[8/1
ALT Increase
$/7∀[8/1EXW[8/1SHUVLVWVIRU∀ZHHNV
$/7∀[8/1EXW[8/1SHUVLVWVIRU∀ZHHNV
Bilirubin1, 2
$/7∀[8/1and ELOLUXELQ∀[8/1!GLUHFWELOLUXELQ
INR2 
$/7∀[8/1and ,15!LI,15PHDVXUHG
Cannot 
Monitor
$/7∀[8/1EXW[8/1DQGFDQQRWEHPRQLWRUHGZHHNO\IRU∀ZHHNV
$/7∀[8/1EXW[8/1DQGFDQQRWEHPRQLWRUHGZHHNO\IRU∀ZHHNV
Symptomatic3
$/7∀[8/1DVVRFLDWHGZLWKV\PSWRPVQHZRUZRUVHQLQJEHOLHYHGWREH
UHODWHGWROLYHULQMXU\RUK\SHUVHQVLWLYLW\
Required Actions and Follow up Assessments following ANY Liver Stopping Event
Actions
Follow Up Assessments
!
,PPHGLDWHO\GLVFRQWLQXHVWXG\WUHDWPHQW
!
5HSRUWWKHHYHQWWR*6. within 24 hours
!
&RPSOHWHWKHOLYHUHYHQW&5)DQGFRPSOHWH
DQ6$(GDWDFROOHFWLRQWRROLIWKHHYHQWDOVR
PHHWVWKHFULWHULDIRUDQ6$(2
!
3HUIRUPOLYHUHYHQWIROORZXSDVVHVVPHQWV
!
0RQLWRUWKHVXEMHFWXQWLOOLYHUFKHPLVWULHV
UHVROYHVWDELOL]HRUUHWXUQWRZLWKLQEDVHOLQH
VHHMONITORING EHORZ
!
Do not restart/rechallenge VXEMHFWZLWK
VWXG\WUHDWPHQWXQOHVVDOORZHGSHUSURWRFRO
DQG*6.0HGLFDO*RYHUQDQFHDSSURYDOis 
!
9LUDOKHSDWLWLVVHURORJ\
!
2QO\LQWKRVHZLWKXQGHUO\LQJFKURQLF
KHSDWLWLV%DWVWXG\ HQWU\LGHQWLILHGE\
SRVLWLYHKHSDWLWLV%VXUIDFHDQWLJHQ
TXDQWLWDWLYHKHSDWLWLV%'1$DQGKHSDWLWLV
GHOWDDQWLERG\
!
%ORRGVDPSOHIRUSKDUPDFRNLQHWLF3.
DQDO\VLVREWDLQHGZLWKLQDIWHUODVWGRVH
!
6HUXPFUHDWLQHSKRVSKRNLQDVH&3.DQG
ODFWDWHGHK\GURJHQDVH/'+
!
)UDFWLRQDWHELOLUXELQLIWRWDO
ELOLUXELQ∀[8/1

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
77
granted UHIHUWR$SSHQGL[
!
,IUHVWDUWUHFKDOOHQJHnot  allowed or not 
grantedSHUPDQHQWO\GLVFRQWLQXHVWXG\
WUHDWPHQWDQGPD\FRQWLQXHVXEMHFWLQWKH
VWXG\IRUDQ\SURWRFROVSHFLILHGIROORZXS
DVVHVVPHQWV
MONITORING:
For bilirubin or INR criteria:
!
5HSHDWOLYHUFKHPLVWULHVLQFOXGH$/7$67
DONDOLQHSKRVSKDWDVHELOLUXELQ DQGSHUIRUP
OLYHUHYHQWIROORZXSDVVHVVPHQWVZLWKLQ24 
hrs
!
0RQLWRUVXEMHFWVWZLFHZHHNO\XQWLOOLYHU
FKHPLVWULHVUHVROYHVWDELOL]HRUUHWXUQWR
ZLWKLQEDVHOLQH
!
$VSHFLDOLVWRUKHSDWRORJ\FRQVXOWDWLRQLV
UHFRPPHQGHG
For All other criteria:
!
5HSHDWOLYHUFKHPLVWULHVLQFOXGH$/7$67
DONDOLQHSKRVSKDWDVHELOLUXELQ DQGSHUIRUP
OLYHUHYHQWIROORZXSDVVHVVPHQWVZLWKLQ24-
72 hrs 
!
0RQLWRUVXEMHFWVZHHNO\XQWLOOLYHUFKHPLVWULHV
UHVROYHVWDELOL]HRUUHWXUQWRZLWKLQEDVHOLQH
!
2EWDLQFRPSOHWHEORRGFRXQWZLWK
GLIIHUHQWLDOWRDVVHVVHRVLQRSKLOLD
!
5HFRUGWKHDSSHDUDQFHRUZRUVHQLQJRI
FOLQLFDOV\PSWRPVRIOLYHULQMXU\RU
K\SHUVHQVLWLYLW\RQWKH$(UHSRUWIRUP
!
5HFRUGXVH RIFRQFRPLWDQWPHGLFDWLRQVRQ
WKHFRQFRPLWDQWPHGLFDWLRQVUHSRUWIRUP
LQFOXGLQJDFHWDPLQRSKHQKHUEDO
UHPHGLHVRWKHURYHUWKHFRXQWHU
PHGLFDWLRQV
!
5HFRUGDOFRKROXVHRQWKHOLYHUHYHQW
DOFRKROLQWDNHFDVHUHSRUWIRUP
For bilirubin or INR criteria:
!
$QWLQXFOHDUDQWLERG\DQWLVPRRWKPXVFOH
DQWLERG\7\SHDQWLOLYHUNLGQH\
PLFURVRPDODQWLERGLHVDQGTXDQWLWDWLYH
WRWDOLPPXQRJOREXOLQ*,J*RUJDPPD
JOREXOLQV
!
6HUXPDFHWDPLQRSKHQDGGXFW+3/&
DVVD\TXDQWLILHVSRWHQWLDODFHWDPLQRSKHQ
FRQWULEXWLRQWROLYHULQMXU\LQVXEMHFWVZLWK
GHILQLWHRUOLNHO\DFHWDPLQRSKHQXVHLQWKH
SUHFHGLQJZHHN>-DPHV@NOTE: 
not required in China
!
/LYHULPDJLQJXOWUDVRXQGPDJQHWLF
UHVRQDQFHRUFRPSXWHULVHGWRPRJUDSK\
DQGRUOLYHUELRSV\WRHYDOXDWHOLYHU
GLVHDVHFRPSOHWH/LYHU,PDJLQJDQGRU
/LYHU%LRSV\&5)IRUPV

6HUXPELOLUXELQIUDFWLRQDWLRQVKRXOGEHSHUIRUPHGLIWHVWLQJLVDYDLODEOH,IVHUXPELOLUXELQIUDFWLRQDWLRQLVQRW
LPPHGLDWHO\DYDLODEOHGLVFRQWLQXHVWXG\WUHDWPHQWIRUWKDWVXEMHFWLI$/7∀[8/1and ELOLUXELQ∀[8/1
$GGLWLRQDOO\LIVHUXPELOLUXELQIUDFWLRQDWLRQWHVWLQJLVXQDYDLODEOHrecord presence of detectable urinary 
bilirubin on dipstickLQGLFDWLQJGLUHFWELOLUXELQHOHYDWLRQVDQGVXJJHVWLQJOLYHULQMXU\

$OOHYHQWVRI$/7∀[8/1and ELOLUXELQ∀[8/1!GLUHFWELOLUXELQRU$/7∀[8/1and ,15!LI,15
PHDVXUHGZKLFKPD\LQGLFDWHVHYHUHOLYHULQMXU\SRVVLEOHµ+\¶V/DZ¶must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis),15PHDVXUHPHQWLVQRWUHTXLUHGDQGWKHWKUHVKROGYDOXHVWDWHG
ZLOOQRWDSSO\WRVXEMHFWVUHFHLYLQJDQWLFRDJXODQWV

1HZRUZRUVHQLQJV\PSWRPVEHOLHYHGWREHUHODWHGWROLYHULQMXU\VXFK DVIDWLJXHQDXVHDYRPLWLQJULJKWXSSHU
TXDGUDQWSDLQRUWHQGHUQHVVRUMDXQGLFHRUEHOLHYHGWREHUHODWHGWRK\SHUVHQVLWLYLW\VXFKDVIHYHUUDVKRU
HRVLQRSKLOLD

+HSDWLWLV$,J0DQWLERG\+HSDWLWLV%VXUIDFHDQWLJHQDQG+HSDWLWLV%&RUH$QWLERG\,J0+HSDWLWLV&51$
&\WRPHJDORYLUXV,J0DQWLERG\(SVWHLQ%DUUYLUDOFDSVLGDQWLJHQ,J0DQWLERG\RULIXQDYDLODEOHREWDLQ
KHWHURSKLOHDQWLERG\RUPRQRVSRWWHVWLQJ+HSDWLWLV(,J0DQWLERG\

,IKHSDWLWLVGHOWDDQWLERG\DVVD\FDQQRWEHSHUIRUPHGLWFDQEHUHSODFHGZLWKD3&5RIKHSDWLWLV'51$YLUXV
ZKHUHQHHGHG>/H*DO@ 3.VDPSOHPD\QRWEHUHTXLUHGIRUVXEMHFWVNQRZQWREHUHFHLYLQJSODFHERRU

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
78
QRQ*6.FRPSDUDWRUWUHDWPHQWV5HFRUGWKHGDWHWLPHRIWKH3.EORRGVDPSOHGUDZDQGWKHGDWHWLPHRIWKHODVW
GRVHRIVWXG\WUHDWPHQWSULRUWREORRGVDPSOHGUDZRQWKH&5),IWKH GDWHRUWLPHRIWKHODVWGRVHLVXQFOHDU
SURYLGHWKHVXEMHFW¶VEHVWDSSUR[LPDWLRQ,IWKHGDWHWLPHRIWKHODVWGRVHFDQQRWEHDSSUR[LPDWHG25D3.
VDPSOHFDQQRWEHFROOHFWHGLQWKHWLPHSHULRGLQGLFDWHGDERYHGRQRWREWDLQD3.VDPSOH,QVWUXFWLRQVIRU VDPSOH
KDQGOLQJDQGVKLSSLQJDUHLQWKH650
3KDVH,,,,9OLYHUFKHPLVWU\LQFUHDVHGPRQLWRULQJFULWHULDZLWKFRQWLQXHGWKHUDS\
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event
Criteria
Actions
$/7∀[8/1DQG [8/1and
ELOLUXELQ[8/1without V\PSWRPV
EHOLHYHGWREHUHODWHGWROLYHULQMXU\RU
K\SHUVHQVLWLYLW\and ZKRFDQEH
PRQLWRUHGZHHNO\IRUZHHNV
25
$/7∀[8/1DQG[8/1and
ELOLUXELQ[8/1without V\PSWRPV
EHOLHYHGWREHUHODWHGWROLYHULQMXU\RU
K\SHUVHQVLWLYLW\and ZKRFDQEH
PRQLWRUHGZHHNO\IRUZHHNV
!
1RWLI\WKH*6.PHGLFDOPRQLWRUwithin 24 hours
RIOHDUQLQJRIWKHDEQRUPDOLW\WRGLVFXVVVXEMHFW
VDIHW\
!
6XEMHFWFDQFRQWLQXHVWXG\WUHDWPHQW
!
6XEMHFWPXVWUHWXUQZHHNO\IRUUHSHDWOLYHU
FKHPLVWULHV$/7$67DONDOLQHSKRVSKDWDVH
ELOLUXELQXQWLOWKH\UHVROYHVWDELOLVHRUUHWXUQWR
ZLWKLQEDVHOLQH
!
,IDWDQ\WLPHVXEMHFWPHHWVWKHOLYHUFKHPLVWU\
VWRSSLQJFULWHULDSURFHHGDVGHVFULEHGDERYH
!
,I$/7GHFUHDVHVIURP$/7∀[8/1DQG [8/1
WR[8/1EXW[8/1FRQWLQXHWRPRQLWRUOLYHU
FKHPLVWULHVZHHNO\
!
,IDIWHUZHHNVRIPRQLWRULQJ$/7[8/1DQG
ELOLUXELQ[8/1PRQLWRUVXEMHFWVWZLFHPRQWKO\
XQWLOOLYHUFKHPLVWULHVQRUPDOL]HRUUHWXUQWRZLWKLQ
EDVHOLQH
5HIHUHQFHV
-DPHV/3/HW]LJ/6LPSVRQ30&DSSDUHOOL(5REHUWV':+LQVRQ-$'DYHUQ7-/HH
:03KDUPDFRNLQHWLFVRI$FHWDPLQRSKHQ$GGXFWLQ$GXOWVZLWK$FHWDPLQRSKHQ
2YHUGRVHDQG$FXWH/LYHU)DLOXUH'UXJ0HWDE'LVSRV
/H*DO)*RUGLHQ($IIRODEL'+DQVOLN7$OORXL&'pQ\3*DXOW(4XDQWLILFDWLRQ
RI+HSDWLWLV'HOWD9LUXV51$LQ6HUXPE\&RQVHQVXV5HDO7LPH3&5,QGLFDWHV
'LIIHUHQW3DWWHUQVRI9LURORJLFDO5HVSRQVHWR,QWHUIHURQ7KHUDS\LQ&KURQLFDOO\,QIHFWHG
3DWLHQWV-&OLQ0LFURELRO±

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
79

$SSHQGL[ 'HILQLWLRQRIDQG3URFHGXUHVIRU5HFRUGLQJ
(YDOXDWLQJ)ROORZ8SDQG5HSRUWLQJRI$GYHUVH(YHQWV

'HILQLWLRQRI$GYHUVH(YHQWV DQG$'5V
$GYHUVH(YHQWDQG$'5V'HILQLWLRQ
!
$Q$(LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHLQDSDWLHQWRUFOLQLFDOLQYHVWLJDWLRQ
VXEMHFWWHPSRUDOO\DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOSURGXFWZKHWKHURUQRW
FRQVLGHUHGUHODWHGWRWKHPHGLFLQDOSURGXFW
!
7KHGHILQLWLRQRIDQ$'5LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHLQDSDWLHQWRUFOLQLFDO
LQYHVWLJDWLRQVXEMHFWWHPSRUDOO\DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOSURGXFWIRU
ZKLFKWKHUHLVDUHDVRQDEOHSRVVLELOLW\WKDWWKHXQWRZDUGRFFXUUHQFHLVFDXVDOO\
UHODWHGWRWKHPHGLFLQDOSURGXFW$'5VDUHDVXEVHWRI$(VIRUDJLYHQPHGLFLQDO
SURGXFW
!
127($Q$(FDQWKHUHIRUHEHDQ\ XQIDYRUDEOH DQGXQLQWHQGHGVLJQLQFOXGLQJDQ
DEQRUPDOODERUDWRU\ILQGLQJV\PSWRPRUGLVHDVHQHZRUH[DFHUEDWHGWHPSRUDOO\
DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOSURGXFW
(YHQWVPHHWLQJ $(GHILQLWLRQLQFOXGH
!
$Q\DEQRUPDOODERUDWRU\WHVWUHVXOWVKHPDWRORJ\FOLQLFDOFKHPLVWU\RUXULQDO\VLV
RURWKHUVDIHW\DVVHVVPHQWVHJ(&*VUDGLRORJLFDOVFDQVYLWDOVLJQV
PHDVXUHPHQWVLQFOXGLQJWKRVHWKDWZRUVHQIURPEDVHOLQHDQGIHOWWREHFOLQLFDOO\
VLJQLILFDQWLQWKHPHGLFDODQGVFLHQWLILFMXGJHPHQWRIWKHLQYHVWLJDWRU
!
([DFHUEDWLRQRIDFKURQLFRULQWHUPLWWHQWSUHH[LVWLQJFRQGLWLRQLQFOXGLQJHLWKHUDQ
LQFUHDVHLQIUHTXHQF\DQGRULQWHQVLW\RIWKHFRQGLWLRQ
!
1HZFRQGLWLRQVGHWHFWHGRUGLDJQRVHGDIWHUVWXG\WUHDWPHQWDGPLQLVWUDWLRQHYHQ
WKRXJKLWPD\KDYHEHHQSUHVHQWSULRUWRWKHVWDUWRIWKHVWXG\
!
6LJQVV\PSWRPVRUWKHFOLQLFDOVHTXHODHRIDVXVSHFWHGLQWHUDFWLRQ
!
6LJQVV\PSWRPVRUWKHFOLQLFDOVHTXHODHRIDVXVSHFWHGRYHUGRVHRIHLWKHUVWXG\
WUHDWPHQWRUDFRQFRPLWDQWPHGLFDWLRQRYHUGRVHSHUVHZLOOQRWEHUHSRUWHGDVDQ
$(6$(XQOHVVWKLVLVDQLQWHQWLRQDORYHUGRVHWDNHQZLWKSRVVLEOHVXLFLGDOVHOI
KDUPLQJLQWHQW7KLVVKRXOGEHUHSRUWHGUHJDUGOHVVRIVHTXHODH
!
/DFNRIHIILFDF\RUIDLOXUHRIH[SHFWHGSKDUPDFRORJLFDODFWLRQSHUVHZLOOQRWEH
UHSRUWHGDVDQ$(RU6$(+RZHYHUWKHVLJQVDQGV\PSWRPVDQGRUFOLQLFDO
VHTXHODHUHVXOWLQJIURPODFNRIHIILFDF\ZLOOEHUHSRUWHGLIWKH\IXOILOWKHGHILQLWLRQ
RIDQ$(RU6$(

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
80
(YHQWV127 PHHWLQJGHILQLWLRQRIDQ$(LQFOXGH
!
$Q\FOLQLFDOO\VLJQLILFDQWDEQRUPDOODERUDWRU\ILQGLQJVRURWKHUDEQRUPDOVDIHW\
DVVHVVPHQWVZKLFKDUHDVVRFLDWHGZLWKWKHXQGHUO\LQJGLVHDVHXQOHVVMXGJHGE\WKH
LQYHVWLJDWRUWREHPRUHVHYHUHWKDQH[SHFWHGIRUWKHVXEMHFW¶VFRQGLWLRQ
!
7KHGLVHDVHGLVRUGHUEHLQJVWXGLHGRUH[SHFWHGSURJUHVVLRQVLJQVRUV\PSWRPVRI
WKHGLVHDVHGLVRUGHUEHLQJVWXGLHGXQOHVVPRUHVHYHUHWKDQH[SHFWHGIRUWKHVXEMHFW¶V
FRQGLWLRQ
!
0HGLFDORUVXUJLFDOSURFHGXUHHJHQGRVFRS\DSSHQGHFWRP\WKHFRQGLWLRQWKDW
OHDGVWRWKHSURFHGXUHLVDQ$(
!
6LWXDWLRQVZKHUHDQXQWRZDUGPHGLFDORFFXUUHQFHGLGQRWRFFXUVRFLDODQGRU
FRQYHQLHQFHDGPLVVLRQWRDKRVSLWDO
!
$QWLFLSDWHGGD\WRGD\IOXFWXDWLRQVRISUHH[LVWLQJGLVHDVHVRUFRQGLWLRQVSUHVHQW
RUGHWHFWHGDWWKHVWDUWRIWKHVWXG\WKDWGRQRWZRUVHQ

'HILQLWLRQRI6HULRXV$GYHUVH(YHQWV
,IDQHYHQWLVQRWDQ$(SHUGHILQLWLRQDERYHWKHQLWFDQQRWEHDQ6$(HYHQLIVHULRXV
FRQGLWLRQVDUHPHWHJKRVSLWDOL]DWLRQIRUVLJQVV\PSWRPVRIWKHGLVHDVHXQGHUVWXG\
GHDWKGXHWRSURJUHVVLRQRIGLVHDVHHWF
6HULRXV$GYHUVH(YHQW6$(LVGHILQHGDVDQ\XQWRZDUGPHGLFDORFFXUUHQFHWKDW
DWDQ\GRVH
D 5HVXOWVLQGHDWK
E ,VOLIHWKUHDWHQLQJ
127(
7KHWHUP
OLIHWKUHDWHQLQJ
LQWKHGHILQLWLRQRI
VHULRXV
UHIHUVWRDQHYHQWLQZKLFKWKH
VXEMHFWZDVDWULVNRIGHDWKDWWKH WLPHRIWKHHYHQW,WGRHVQRWUHIHUWRDQHYHQWZKLFK
K\SRWKHWLFDOO\PLJKWKDYHFDXVHGGHDWKLILWZHUHPRUHVHYHUH
F 5HTXLUHVKRVSLWDOL]DWLRQRUSURORQJDWLRQRIH[LVWLQJKRVSLWDOL]DWLRQ
127(
!
,QJHQHUDOKRVSLWDOL]DWLRQVLJQLILHVWKDWWKHVXEMHFWKDV EHHQGHWDLQHGXVXDOO\
LQYROYLQJDWOHDVWDQRYHUQLJKWVWD\DWWKHKRVSLWDORUHPHUJHQF\ZDUGIRU
REVHUYDWLRQDQGRUWUHDWPHQWWKDWZRXOGQRWKDYHEHHQDSSURSULDWHLQWKHSK\VLFLDQ¶V
RIILFHRURXWSDWLHQW VHWWLQJ&RPSOLFDWLRQVWKDWRFFXUGXULQJKRVSLWDOL]DWLRQDUH
$(V,IDFRPSOLFDWLRQSURORQJVKRVSLWDOL]DWLRQRU IXOILOOV DQ\RWKHUVHULRXVFULWHULD
WKHHYHQWLVVHULRXV:KHQLQGRXEWDVWRZKHWKHU³KRVSLWDOL]DWLRQ´RFFXUUHGRUZDV
QHFHVVDU\WKH$(VKRXOGEHFRQVLGHUHGVHULRXV
!
+RVSLWDOL]DWLRQIRUHOHFWLYHWUHDWPHQWRIDSUHH[LVWLQJFRQGLWLRQWKDWGLGQRWZRUVHQ

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
81
IURPEDVHOLQHLVQRWFRQVLGHUHGDQ$(
G 5HVXOWVLQGLVDELOLW\LQFDSDFLW\
127(
!
7KHWHUPGLVDELOLW\PHDQVDVXEVWDQWLDOGLVUXSWLRQRIDSHUVRQ¶VDELOLW\WRFRQGXFW
QRUPDOOLIHIXQFWLRQV
!
7KLV GHILQLWLRQLVQRWLQWHQGHGWRLQFOXGHH[SHULHQFHVRIUHODWLYHO\PLQRUPHGLFDO
VLJQLILFDQFHVXFKDVXQFRPSOLFDWHGKHDGDFKHQDXVHDYRPLWLQJ GLDUUKHDLQIOXHQ]D
DQGDFFLGHQWDOWUDXPDHJVSUDLQHGDQNOHZKLFKPD\LQWHUIHUHRUSUHYHQWHYHU\GD\
OLIHIXQFWLRQVEXWGRQRWFRQVWLWXWHDVXEVWDQWLDOGLVUXSWLRQ
H ,VDFRQJHQLWDODQRPDO\ELUWKGHIHFW
I
2WKHUVLWXDWLRQV
!
0HGLFDORUVFLHQWLILFMXGJPHQWVKRXOGEHH[HUFLVHGLQGHFLGLQJZKHWKHUUHSRUWLQJLV
DSSURSULDWHLQRWKHUVLWXDWLRQVVXFKDVLPSRUWDQWPHGLFDOHYHQWVWKDWPD\QRWEH
LPPHGLDWHO\OLIHWKUHDWHQLQJRUUHVXOWLQGHDWKRUKRVSLWDOL]DWLRQEXWPD\MHRSDUGL]H
WKHVXEMHFWRUPD\UHTXLUHPHGLFDORUVXUJLFDOLQWHUYHQWLRQWRSUHYHQWRQHRIWKH
RWKHURXWFRPHVOLVWHGLQWKHDERYHGHILQLWLRQ7KHVHVKRXOGDOVREH FRQVLGHUHG
VHULRXV
!
([DPSOHVRIVXFKHYHQWVDUHLQYDVLYHRUPDOLJQDQWFDQFHUVLQWHQVLYHWUHDWPHQWLQDQ
HPHUJHQF\URRPRUDWKRPHIRUDOOHUJLFEURQFKRVSDVPEORRGG\VFUDVLDVRU
FRQYXOVLRQVWKDWGRQRWUHVXOWLQKRVSLWDOL]DWLRQRUGHYHORSPHQWRIGUXJGHSHQGHQF\
RUGUXJDEXVH
J ,VDVVRFLDWHGZLWKOLYHULQMXU\DQG LPSDLUHGOLYHUIXQFWLRQGHILQHGDV
!
$/7∀[8/1DQGWRWDOELOLUXELQ ∀[8/1!GLUHFWRU
!
$/7∀[8/1DQG,15 !
6HUXPELOLUXELQIUDFWLRQDWLRQVKRXOGEHSHUIRUPHGLIWHVWLQJLVDYDLODEOHLIXQDYDLODEOH
PHDVXUHXULQDU\ELOLUXELQYLDGLSVWLFN,IIUDFWLRQDWLRQLVXQDYDLODEOHDQG$/7∀[8/1
DQGWRWDOELOLUXELQ∀[8/1WKHQWKHHYHQWLVVWLOOWREHUHSRUWHGDVDQ6$(
,15WHVWLQJQRWUHTXLUHGSHUSURWRFRODQGWKHWKUHVKROGYDOXHGRHVQRWDSSO\WR
VXEMHFWVUHFHLYLQJDQWLFRDJXODQWV,I,15PHDVXUHPHQWLVREWDLQHGWKHYDOXHLVWREH
UHFRUGHGRQWKH6$(IRUP
!
5HIHUWR$SSHQGL[ IRUWKHUHTXLUHGOLYHUFKHPLVWU\IROORZXSLQVWUXFWLRQV

'HILQLWLRQRI&DUGLRYDVFXODU(YHQWV
&DUGLRYDVFXODU(YHQWV&9'HILQLWLRQ
,QYHVWLJDWRUVZLOOEHUHTXLUHGWRILOORXWWKHVSHFLILF&9HYHQWSDJHRIWKH&5)IRUWKH
IROORZLQJ$(VDQG6$(V

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
82
!
0\RFDUGLDOLQIDUFWLRQXQVWDEOHDQJLQD
!
&RQJHVWLYHKHDUWIDLOXUH
!
$UUK\WKPLDV
!
9DOYXORSDWK\
!
3XOPRQDU\K\SHUWHQVLRQ
!
&HUHEURYDVFXODUHYHQWVVWURNHDQGWUDQVLHQWLVFKHPLFDWWDFN
!
3HULSKHUDODUWHULDOWKURPERHPEROLVP
!
'HHSYHQRXVWKURPERVLVSXOPRQDU\HPEROLVP
!
5HYDVFXODUL]DWLRQ

5HFRUGLQJRI$(V$'5VDQG6$(V
$(VDQG6$(5HFRUGLQJ
!
:KHQDQ$( $'5V6$(RFFXUVLWLVWKHUHVSRQVLELOLW\RIWKHLQYHVWLJDWRUWR
UHYLHZDOOGRFXPHQWDWLRQHJKRVSLWDOSURJUHVVQRWHVODERUDWRU\DQGGLDJQRVWLFV
UHSRUWVUHODWLYHWRWKHHYHQW
!
7KHLQYHVWLJDWRUZLOOWKHQUHFRUGDOOUHOHYDQWLQIRUPDWLRQUHJDUGLQJDQ$( $'5V
6$(LQWKH&5)
!
,WLVQRW DFFHSWDEOHIRUWKHLQYHVWLJDWRUWRVHQGSKRWRFRSLHVRIWKHVXEMHFW¶VPHGLFDO
UHFRUGVWR*6.LQOLHXRIFRPSOHWLRQRIWKH*6.$( $'5V6$(&5)SDJH
!
7KHUHPD\EHLQVWDQFHVZKHQFRSLHVRIPHGLFDOUHFRUGVIRUFHUWDLQFDVHVDUH
UHTXHVWHGE\*6.,QWKLVLQVWDQFHDOOVXEMHFWLGHQWLILHUVZLWKWKHH[FHSWLRQRIWKH
VXEMHFWQXPEHUZLOOEHEOLQGHGRQWKHFRSLHVRIWKHPHGLFDOUHFRUGVSULRUWR
VXEPLVVLRQRIWR*6.
!
7KHLQYHVWLJDWRUZLOODWWHPSWWRHVWDEOLVKDGLDJQRVLVRIWKHHYHQWEDVHGRQVLJQV
V\PSWRPVDQGRURWKHUFOLQLFDOLQIRUPDWLRQ,QVXFKFDVHVWKHGLDJQRVLVZLOOEH
GRFXPHQWHGDVWKH$( $'5V6$(DQGQRWWKHLQGLYLGXDOVLJQVV\PSWRPV
!
6XEMHFWFRPSOHWHG9DOXH(YLGHQFHDQG2XWFRPHVTXHVWLRQQDLUHVDQGWKHFROOHFWLRQ
RI$($'5VGDWDDUHLQGHSHQGHQW FRPSRQHQWVRIWKHVWXG\
!
5HVSRQVHVWRHDFKTXHVWLRQLQWKH9DOXH(YLGHQFHDQG2XWFRPHVTXHVWLRQQDLUHZLOO
EHWUHDWHGLQDFFRUGDQFHZLWKVWDQGDUGVFRULQJDQGVWDWLVWLFDOSURFHGXUHVGHWDLOHGE\
WKHVFDOH¶VGHYHORSHU
!
7KHXVHRIDVLQJOHTXHVWLRQIURPDPXOWLGLPHQVLRQDOKHDOWKVXUYH\WRGHVLJQDWHD
FDXVHHIIHFWUHODWLRQVKLSWRDQ$($'5VLVLQDSSURSULDWH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
83

(YDOXDWLQJ$(V$'5VDQG6$(V
$VVHVVPHQWRI,QWHQVLW\
7KHLQYHVWLJDWRUZLOOPDNHDQDVVHVVPHQWRILQWHQVLW\IRUHDFK$($'5VDQG6$(
UHSRUWHGGXULQJ WKHVWXG\DQGZLOODVVLJQLWWRRQHRIWKHIROORZLQJFDWHJRULHV
!
0LOG$QHYHQWWKDWLVHDVLO\WROHUDWHGE\WKHVXEMHFWFDXVLQJPLQLPDOGLVFRPIRUW
DQGQRWLQWHUIHULQJZLWKHYHU\GD\DFWLYLWLHV
!
0RGHUDWH$QHYHQWWKDWLVVXIILFLHQWO\GLVFRPIRUWLQJWRLQWHUIHUHZLWKQRUPDO
HYHU\GD\DFWLYLWLHV
!
6HYHUH$QHYHQWWKDWSUHYHQWVQRUPDOHYHU\GD\DFWLYLWLHV DQ$($'5VWKDWLV
DVVHVVHGDVVHYHUHZLOOQRWEHFRQIXVHGZLWKDQ6$(6HYHULW\LVDFDWHJRU\XWLOL]HG
IRUUDWLQJWKHLQWHQVLW\RIDQHYHQWDQGERWK$(V $'5V DQG6$(VFDQEHDVVHVVHG
DVVHYHUH
!
$QHYHQWLVGHILQHGDVµVHULRXV¶ZKHQLWPHHWVDWOHDVWRQHRIWKHSUHGHILQHG
RXWFRPHVDVGHVFULEHGLQWKHGHILQLWLRQRIDQ6$(
$VVHVVPHQWRI&DXVDOLW\
!
7KHLQYHVWLJDWRULVREOLJDWHGWRDVVHVVWKHUHODWLRQVKLSEHWZHHQVWXG\WUHDWPHQWDQG
WKHRFFXUUHQFHRIHDFK$(6$(
!
$UHDVRQDEOHSRVVLELOLW\LVPHDQWWRFRQYH\WKDWWKHUHDUHIDFWVHYLGHQFHRU
DUJXPHQWVWRVXJJHVWDFDXVDOUHODWLRQVKLSUDWKHUWKDQDUHODWLRQVKLSFDQQRWEHUXOHG
RXW
!
7KHLQYHVWLJDWRUZLOOXVHFOLQLFDOMXGJPHQWWRGHWHUPLQHWKHUHODWLRQVKLS
!
$OWHUQDWLYHFDXVHVVXFKDVQDWXUDOKLVWRU\RIWKHXQGHUO\LQJGLVHDVHVFRQFRPLWDQW
WKHUDS\RWKHUULVNIDFWRUVDQGWKHWHPSRUDOUHODWLRQVKLSRIWKHHYHQWWRWKHVWXG\
WUHDWPHQWZLOOEHFRQVLGHUHGDQGLQYHVWLJDWHG
!
7KHLQYHVWLJDWRUZLOODOVRFRQVXOWWKH,QYHVWLJDWRU%URFKXUH,%DQGRU3URGXFW
,QIRUPDWLRQIRUPDUNHWHGSURGXFWVLQWKHGHWHUPLQDWLRQRIKLVKHUDVVHVVPHQW
!
)RUHDFK$(6$(WKHLQYHVWLJDWRUPXVW GRFXPHQWLQWKHPHGLFDOQRWHVWKDWKHVKH
KDVUHYLHZHGWKH$(6$(DQGKDVSURYLGHGDQDVVHVVPHQWRIFDXVDOLW\
!
7KHUHPD\EHVLWXDWLRQVZKHQDQ6$(KDVRFFXUUHGDQGWKHLQYHVWLJDWRUKDVPLQLPDO
LQIRUPDWLRQWRLQFOXGHLQWKHLQLWLDOUHSRUWWR*6.+RZHYHULWLVYHU\LPSRUWDQW
WKDWWKHLQYHVWLJDWRUDOZD\VPDNHDQDVVHVVPHQWRIFDXVDOLW\IRUHYHU\HYHQW
SULRUWRWKHLQLWLDOWUDQVPLVVLRQRIWKH6$(GDWDWR*6.
!
7KHLQYHVWLJDWRUPD\FKDQJHKLVKHURSLQLRQRIFDXVDOLW\LQOLJKWRIIROORZXS
LQIRUPDWLRQDPHQGLQJWKH6$(GDWDFROOHFWLRQWRRODFFRUGLQJO\
!
7KHFDXVDOLW\DVVHVVPHQWLVRQHRIWKHFULWHULDXVHGZKHQGHWHUPLQLQJUHJXODWRU\
UHSRUWLQJUHTXLUHPHQWV

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
84
)ROORZXSRI$(VDQG6$(V
!
7KHLQYHVWLJDWRULVREOLJDWHGWRSHUIRUPRUDUUDQJHIRUWKHFRQGXFWRIVXSSOHPHQWDO
PHDVXUHPHQWVDQGRUHYDOXDWLRQV DVPD\EHLQGLFDWHGRUDVUHTXHVWHGE\*6.WR
HOXFLGDWHDVIXOO\DVSRVVLEOHWKHQDWXUHDQGRUFDXVDOLW\RIWKH$(RU6$(
!
7KHLQYHVWLJDWRULVREOLJDWHGWRDVVLVW7KLVPD\LQFOXGHDGGLWLRQDOODERUDWRU\WHVWV
RULQYHVWLJDWLRQVKLVWRSDWKRORJLFDOH[DPLQDWLRQVRUFRQVXOWDWLRQZLWKRWKHUKHDOWK
FDUHSURIHVVLRQDOV
!
,IDVXEMHFWGLHVGXULQJSDUWLFLSDWLRQLQWKHVWXG\RUGXULQJDUHFRJQL]HGIROORZXS
SHULRGWKHLQYHVWLJDWRUZLOOSURYLGH*6.ZLWKDFRS\RIDQ\SRVWPRUWHPILQGLQJV
LQFOXGLQJKLVWRSDWKRORJ\
!
1HZ RUXSGDWHGLQIRUPDWLRQZLOOEHUHFRUGHGLQWKHRULJLQDOO\FRPSOHWHG&5)
!
7KHLQYHVWLJDWRUZLOOVXEPLWDQ\XSGDWHG6$(GDWDWR*6.ZLWKLQWKHGHVLJQDWHG
UHSRUWLQJWLPHIUDPHV

5HSRUWLQJRI6$(VWR*6.
6$(UHSRUWLQJWR*6.YLDHOHFWURQLFGDWDFROOHFWLRQWRRO
!
3ULPDU\PHFKDQLVPIRUUHSRUWLQJ6$(VWR*6.ZLOOEHWKHHOHFWURQLFGDWDFROOHFWLRQ
WRRO
!
,IWKHHOHFWURQLFV\VWHPLVXQDYDLODEOHIRUJUHDWHUWKDQKRXUVWKHVLWHZLOOXVHWKH
SDSHU6$(GDWDFROOHFWLRQWRRODQGID[LWWRWKH6$(FRRUGLQDWRU
!
6LWHZLOOHQWHUWKHVHULRXVDGYHUVHHYHQWGDWDLQWRWKHHOHFWURQLFV\VWHPDVVRRQDVLW
EHFRPHVDYDLODEOH
!
7KHLQYHVWLJDWRUZLOOEHUHTXLUHGWRFRQILUPUHYLHZRIWKH6$(FDXVDOLW\E\WLFNLQJ
WKHµUHYLHZHG¶ER[DWWKHERWWRPRIWKHH&5)SDJHZLWKLQKRXUVRIVXEPLVVLRQRI
WKH6$(
!
$IWHUWKHVWXG\LVFRPSOHWHGDWDJLYHQVLWHWKHHOHFWURQLFGDWDFROOHFWLRQWRROHJ
,Q)RUPV\VWHPZLOOEHWDNHQRIIOLQHWRSUHYHQWWKHHQWU\RIQHZGDWDRUFKDQJHVWR
H[LVWLQJGDWD
!
,IDVLWHUHFHLYHVDUHSRUWRIDQHZ6$(IURPDVWXG\VXEMHFWRUUHFHLYHVXSGDWHGGDWD
RQDSUHYLRXVO\UHSRUWHG6$(DIWHUWKHHOHFWURQLFGDWDFROOHFWLRQWRROKDVEHHQWDNHQ
RIIOLQHWKHVLWHFDQUHSRUWWKLVLQIRUPDWLRQRQDSDSHU6$(IRUPRUWRWKH6$(
FRRUGLQDWRUE\WHOHSKRQH
!
&RQWDFWVIRU6$(UHFHLSWFDQEHIRXQGDWWKHEHJLQQLQJRIWKLVSURWRFRORQWKH
6SRQVRU0HGLFDO0RQLWRU&RQWDFW,QIRUPDWLRQSDJH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
85

$SSHQGL[*HQHWLF5HVHDUFK
*HQHWLF5HVHDUFK2EMHFWLYHVDQG$QDO\VHV
7KHREMHFWLYHVRIWKHJHQHWLFUHVHDUFKDUHWRLQYHVWLJDWHWKHUHODWLRQVKLSEHWZHHQJHQHWLF
YDULDQWVDQG
!
5HVSRQVHWRPHGLFLQHLQFOXGLQJDQ\WUHDWPHQWUHJLPHQVXQGHULQYHVWLJDWLRQLQ
WKLVVWXG\RUDQ\FRQFRPLWDQWPHGLFLQHV
!
$VWKPD VXVFHSWLELOLW\VHYHULW\DQGSURJUHVVLRQDQGUHODWHGFRQGLWLRQV
*HQHWLFGDWDPD\EHJHQHUDWHGZKLOHWKHVWXG\LVXQGHUZD\RUIROORZLQJFRPSOHWLRQRI
WKHVWXG\*HQHWLFHYDOXDWLRQVPD\LQFOXGHIRFXVHGFDQGLGDWHJHQHDSSURDFKHVDQGRU
H[DPLQDWLRQRIDODUJHQXPEHURIJHQHWLFYDULDQWVWKURXJKRXWWKHJHQRPHZKROHJHQRPH
DQDO\VHV*HQHWLFDQDO\VHVZLOOXWLOL]HGDWDFROOHFWHGLQWKHVWXG\DQGZLOOEHOLPLWHGWR
XQGHUVWDQGLQJWKHREMHFWLYHVKLJKOLJKWHGDERYH$QDO\VHVPD\EHSHUIRUPHGXVLQJGDWD
IURPPXOWLSOHFOLQLFDOVWXGLHVWRLQYHVWLJDWHWKHVHUHVHDUFKREMHFWLYHV
$SSURSULDWHGHVFULSWLYHDQGRUVWDWLVWLFDODQDO\VLVPHWKRGVZLOOEHXVHG$GHWDLOHG
GHVFULSWLRQRIDQ\SODQQHGDQDO\VHVZLOOEHGRFXPHQWHGLQD5HSRUWLQJDQG$QDO\VLV3ODQ
5$3SULRUWRLQLWLDWLRQRIWKHDQDO\VLV3ODQQHGDQDO\VHVDQGUHVXOWVRIJHQHWLF
LQYHVWLJDWLRQVZLOOEHUHSRUWHGHLWKHUDVSDUWRIWKHFOLQLFDO5$3DQGVWXG\UHSRUWRULQD
VHSDUDWHJHQHWLFV5$3DQGUHSRUWDVDSSURSULDWH
6WXG\3RSXODWLRQ
$Q\VXEMHFWZKRLVHQUROOHGLQWKHVWXG\FDQSDUWLFLSDWHLQJHQHWLFUHVHDUFK$Q\VXEMHFW
ZKRKDVUHFHLYHGDQ DOORJHQHLF ERQHPDUURZWUDQVSODQWPXVWEHH[FOXGHGIURPWKH
JHQHWLFUHVHDUFK
6WXG\$VVHVVPHQWVDQG3URFHGXUHV
$NH\FRPSRQHQWRIVXFFHVVIXOJHQHWLFUHVHDUFKLVWKHFROOHFWLRQRIVDPSOHVGXULQJ
FOLQLFDOVWXGLHV&ROOHFWLRQRIVDPSOHVHYHQZKHQQRDSULRUL K\SRWKHVLVKDVEHHQ
LGHQWLILHGPD\HQDEOHIXWXUHJHQHWLFDQDO\VHVWREHFRQGXFWHGWRKHOSXQGHUVWDQG
YDULDELOLW\LQGLVHDVHDQGPHGLFLQHUHVSRQVH
!
$POVDOLYDVDPSOHZLOOEHWDNHQIRU'HR[\ULERQXFOHLFDFLG'1$H[WUDFWLRQ
$VDOLYDVDPSOHLVFROOHFWHGDWWKHEDVHOLQHYLVLW 9LVLWDIWHUWKHVXEMHFWKDV
EHHQUDQGRPL]HGDQGSURYLGHGLQIRUPHGFRQVHQWIRUJHQHWLFUHVHDUFK,QVWUXFWLRQV
IRUFROOHFWLRQDQGVKLSSLQJRIWKHJHQHWLFVDPSOHDUHGHVFULEHGLQWKHODERUDWRU\
PDQXDO7KH'1$IURPWKHVDOLYDVDPSOHPD\XQGHUJRTXDOLW\FRQWURODQDO\VHVWR
FRQILUPWKHLQWHJULW\RIWKHVDPSOH,IWKHUHDUHFRQFHUQVUHJDUGLQJWKHTXDOLW\RI
WKHVDPSOHWKHQWKHVDPSOHPD\EHGHVWUR\HG7KHVDOLYDVDPSOHLVWDNHQRQD
VLQJOHRFFDVLRQXQOHVVDGXSOLFDWHVDPSOHLVUHTXLUHGGXHWRDQLQDELOLW\WRXWLOL]H
WKHRULJLQDOVDPSOH
7KHJHQHWLFVDPSOHLVODEHOOHGRU³FRGHG´ZLWKWKHVDPHVWXG\VSHFLILFQXPEHUXVHGWR
ODEHORWKHUVDPSOHVDQGGDWDLQWKHVWXG\7KLVQXPEHUFDQEH WUDFHGRUOLQNHGEDFNWRWKH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
86
VXEMHFWE\WKHLQYHVWLJDWRURUVLWHVWDII&RGHGVDPSOHVGRQRWFDUU\SHUVRQDOLGHQWLILHUV
VXFKDVQDPHRUVRFLDOVHFXULW\QXPEHU
6DPSOHVZLOOEHVWRUHGVHFXUHO\DQGPD\EHNHSWIRUXSWR\HDUVDIWHUWKHODVWVXEMHFW
FRPSOHWHVWKHVWXG\RU*6.PD\GHVWUR\WKHVDPSOHVVRRQHU*6.RUWKRVHZRUNLQJ
ZLWK*6.IRUH[DPSOHRWKHUUHVHDUFKHUVZLOORQO\XVHVDPSOHVFROOHFWHGIURPWKHVWXG\
IRUWKHSXUSRVHVWDWHGLQWKLVSURWRFRODQGLQWKHLQIRUPHGFRQVHQWIRUP6DPSOHVPD\EH
XVHGDVSDUWRIWKHGHYHORSPHQWRIDFRPSDQLRQGLDJQRVWLFWRVXSSRUWWKH*6.PHGLFLQDO
SURGXFW
6XEMHFWVFDQUHTXHVWWKHLUVDPSOHWREHGHVWUR\HGDWDQ\WLPH
,QIRUPHG&RQVHQW
6XEMHFWVZKRGRQRWZLVKWRSDUWLFLSDWHLQWKHJHQHWLFUHVHDUFKPD\VWLOOSDUWLFLSDWHLQWKH
VWXG\*HQHWLFLQIRUPHGFRQVHQWPXVWEHREWDLQHGSULRUWRDQ\VDOLYDEHLQJWDNHQ
6XEMHFW:LWKGUDZDOIURP6WXG\
,IDVXEMHFWZKRKDVFRQVHQWHGWRSDUWLFLSDWHLQJHQHWLFUHVHDUFKZLWKGUDZVIURPWKH
FOLQLFDOVWXG\IRUDQ\UHDVRQRWKHUWKDQEHLQJORVWWRIROORZXSWKHVXEMHFWZLOOEHJLYHQD
FKRLFHRIRQHRIWKHIROORZLQJRSWLRQVFRQFHUQLQJWKHJHQHWLFVDPSOHLIDOUHDG\
FROOHFWHG
!
&RQWLQXHWRSDUWLFLSDWHLQWKHJHQHWLFUHVHDUFKLQZKLFKFDVHWKHJHQHWLF'1$
VDPSOHLVUHWDLQHG
!
'LVFRQWLQXHSDUWLFLSDWLRQLQWKHJHQHWLFUHVHDUFKDQGGHVWUR\WKHJHQHWLF'1$
VDPSOH
,IDVXEMHFWZLWKGUDZVFRQVHQWIRUJHQHWLFUHVHDUFKRUUHTXHVWVVDPSOHGHVWUXFWLRQIRUDQ\
UHDVRQWKHLQYHVWLJDWRUPXVWFRPSOHWHWKHDSSURSULDWHGRFXPHQWDWLRQWRUHTXHVWVDPSOH
GHVWUXFWLRQZLWKLQWKHWLPHIUDPHVSHFLILHGE\*6.DQGPDLQWDLQWKHGRFXPHQWDWLRQLQ
WKHVLWHVWXG\UHFRUGV
*HQRW\SHGDWDPD\EHJHQHUDWHGGXULQJWKHVWXG\RUDIWHUFRPSOHWLRQRIWKHVWXG\DQG
PD\EHDQDO\]HGGXULQJWKHVWXG\RUVWRUHGIRUIXWXUHDQDO\VLV
!
,IDVXEMHFWZLWKGUDZVFRQVHQWIRUJHQHWLFUHVHDUFKDQGJHQRW\SHGDWDKDVQRWEHHQ
DQDO\]HGLWZLOOQRWEHDQDO\]HGRUXVHGIRUIXWXUHUHVHDUFK
!
*HQHWLFGDWDWKDWKDVEHHQDQDO\]HGDWWKHWLPHRIZLWKGUDZQFRQVHQWZLOO
FRQWLQXHWREHVWRUHGDQGXVHGDVDSSURSULDWH
6FUHHQDQG%DVHOLQH)DLOXUHV
,IDVDPSOHIRUJHQHWLFUHVHDUFKKDVEHHQFROOHFWHGDQGLWLVGHWHUPLQHGWKDWWKHVXEMHFW
GRHVQRWPHHWWKHHQWU\FULWHULDIRUSDUWLFLSDWLRQLQWKHVWXG\WKHQWKHLQYHVWLJDWRUVKRXOG
LQVWUXFWWKHVXEMHFWWKDWWKHLU JHQHWLFVDPSOHZLOOEHGHVWUR\HG1RIRUPVDUHUHTXLUHGWR
FRPSOHWHWKLVSURFHVVDVLWZLOOEHFRPSOHWHGDVSDUWRIWKHFRQVHQWDQGVDPSOH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
87
UHFRQFLOLDWLRQSURFHVV,QWKLVLQVWDQFHDVDPSOHGHVWUXFWLRQIRUPZLOOQRWEHDYDLODEOHWR
LQFOXGHLQWKHVLWHILOHV
3URYLVLRQRI6WXG\5HVXOWVDQG&RQILGHQWLDOLW\RI6XEMHFW¶V*HQHWLF'DWD
*6. PD\ VXPPDUL]H WKH JHQHWLF UHVHDUFK UHVXOWV LQ WKH FOLQLFDO VWXG\ UHSRUW RU
VHSDUDWHO\DQGPD\SXEOLVKWKHUHVXOWVLQVFLHQWLILFMRXUQDOV
*6. PD\ VKDUH JHQHWLF UHVHDUFK GDWD ZLWK RWKHU VFLHQWLVWV WR IXUWKHU VFLHQWLILF
XQGHUVWDQGLQJLQDOLJQPHQWZLWKWKHLQIRUPHGFRQVHQW*6.GRHVQRWLQIRUPWKHVXEMHFW
IDPLO\ PHPEHUV LQVXUHUV RU HPSOR\HUV RI LQGLYLGXDO JHQRW\SLQJ UHVXOWV WKDW DUH QRW
NQRZQ WR EH UHOHYDQW WR WKH VXEMHFW¶V PHGLFDO FDUH DW WKH WLPH RI WKH VWXG\ XQOHVV
UHTXLUHG E\ ODZ 7KLV LV GXH WR WKH IDFW WKDW WKH LQIRUPDWLRQ JHQHUDWHG IURP JHQHWLF
VWXGLHV LV JHQHUDOO\ SUHOLPLQDU\ LQQDWXUHDQGWKHUHIRUHWKHVLJQLILFDQFH DQGVFLHQWLILF
YDOLGLW\RIWKHUHVXOWVDUHXQGHWHUPLQHG)XUWKHUGDWDJHQHUDWHGLQDUHVHDUFKODERUDWRU\
PD\QRWPHHWUHJXODWRU\UHTXLUHPHQWVIRULQFOXVLRQLQFOLQLFDOFDUH

2017N339371_00

2014N190259_00
&21),'(17,$/
HZA116492
88

$SSHQGL[&ROOHFWLRQRI3UHJQDQF\,QIRUPDWLRQ
!
,QYHVWLJDWRUZLOOFROOHFWSUHJQDQF\LQIRUPDWLRQRQDQ\IHPDOHVXEMHFWZKREHFRPHV
SUHJQDQWZKLOHSDUWLFLSDWLQJLQWKLVVWXG\
!
,QIRUPDWLRQZLOOEHUHFRUGHGRQWKHDSSURSULDWHIRUPDQGVXEPLWWHGWR*6.ZLWKLQ
ZHHNVRIOHDUQLQJRIDVXEMHFW
VSUHJQDQF\
!
6XEMHFW ZLOO EH IROORZHG WR GHWHUPLQH WKH RXWFRPH RI WKH SUHJQDQF\ 7KH
LQYHVWLJDWRUZLOOFROOHFWIROORZXSLQIRUPDWLRQRQPRWKHUDQGLQIDQWZKLFKZLOOEH
IRUZDUGHGWR*6.*HQHUDOO\IROORZXSZLOOQRWEHUHTXLUHGIRUORQJHUWKDQWR
ZHHNVEH\RQGWKHHVWLPDWHGGHOLYHU\GDWH
!
$Q\WHUPLQDWLRQRISUHJQDQF\ZLOOEHUHSRUWHGUHJDUGOHVVRIIRHWDO VWDWXVSUHVHQFH
RUDEVHQFHRIDQRPDOLHVRULQGLFDWLRQIRUSURFHGXUH
!
:KLOH SUHJQDQF\ LWVHOI LV QRW FRQVLGHUHG WR EH DQ $( RU 6$( DQ\ SUHJQDQF\
FRPSOLFDWLRQRU HOHFWLYHWHUPLQDWLRQRI DSUHJQDQF\ ZLOOEHUHSRUWHGDV DQ$( RU
6$(
!
$VSRQWDQHRXVDERUWLRQLVDOZD\VFRQVLGHUHGWREHDQ6$(DQGZLOOEHUHSRUWHGDV
VXFK
!
$Q\ 6$( RFFXUULQJ DV D UHVXOW RI D SRVWVWXG\ SUHJQDQF\ ZKLFK LV FRQVLGHUHG
UHDVRQDEO\UHODWHGWRWKHVWXG\WUHDWPHQWE\WKHLQYHVWLJDWRU ZLOOEHUHSRUWHGWR*6.
DVGHVFULEHGLQ$SSHQGL[ :KLOHWKHLQYHVWLJDWRULVQRWREOLJDWHGWRDFWLYHO\VHHN
WKLVLQIRUPDWLRQLQIRUPHUVWXG\SDUWLFLSDQWVKHRUVKHPD\OHDUQRIDQ6$(WKURXJK
VSRQWDQHRXVUHSRUWLQJ
$Q\IHPDOHVXEMHFWZKREHFRPHVSUHJQDQWZKLOHSDUWLFLSDWLQJ
!
ZLOOEHZLWKGUDZQIURPWKHVWXG\
!
7KLVZLOORQO\EHLQFOXGHGLIHLWKHURIWKHIROORZLQJDSSO\
!
,QYHVWLJDWRUZLOODWWHPSWWRFROOHFWSUHJQDQF\LQIRUPDWLRQRQDQ\IHPDOHSDUWQHURID
PDOH VWXG\ VXEMHFW ZKR EHFRPHV SUHJQDQW ZKLOH SDUWLFLSDWLQJ LQ WKLV VWXG\ 7KLV
DSSOLHVRQO\WRVXEMHFWVZKRDUHUDQGRPL]HGWRUHFHLYHVWXG\PHGLFDWLRQ
!
$IWHU REWDLQLQJ WKH QHFHVVDU\ VLJQHG LQIRUPHG FRQVHQW IURP WKH IHPDOH SDUWQHU
GLUHFWO\WKHLQYHVWLJDWRUZLOOUHFRUGSUHJQDQF\LQIRUPDWLRQRQWKHDSSURSULDWHIRUP
DQGVXEPLWLWWR*6.ZLWKLQZHHNVRIOHDUQLQJRIWKHSDUWQHU¶VSUHJQDQF\
!
3DUWQHU ZLOO DOVR EH IROORZHG WR GHWHUPLQH WKH RXWFRPH RI WKH SUHJQDQF\
,QIRUPDWLRQRQWKHVWDWXVRIWKHPRWKHUDQGFKLOGZLOOEHIRUZDUGHGWR*6.
*HQHUDOO\IROORZXSZLOOEHQRORQJHUWKDQWRZHHNVIROORZLQJWKHHVWLPDWHGGHOLYHU\
GDWH $Q\ WHUPLQDWLRQ RI WKH SUHJQDQF\ ZLOO EH UHSRUWHG UHJDUGOHVV RI IHWDO VWDWXV
SUHVHQFH RU DEVHQFH RI DQRPDOLHV RU LQGLFDWLRQ IRU SURFHGXUH $GGLWLRQDO UHIHUHQFHV
VXSSRUWLQJ WKH UDWLRQDOH IRU JHQHWLF UHVHDUFK RQ WKH VWXG\ WUHDWPHQW FDQ EH LQVHUWHG LI
DYDLODEOH

2017N339371_00