Conditions: Healthy Male
Keywords: Phase 1 Healthy volunteers Pharmacokinetics
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 13
Healthy volunteers: yes

Brief summary:
The primary objective of this study was to determine the effect of the moderate cytochrome P450 3A (CYP3A) inducer rifabutin on the pharmacokinetics (PK) of zanubrutinib in healthy males.

Detailed description:

Arms:
arm 1: Day 1: zanubrutinib

Days 3 to 10: rifabutin

Day 11: zanubrutinib and rifabutin

Interventions: intervention 1: Zanubrutinib intervention 2: Rifabutin
Intervention descriptions: intervention 1: Single oral dose of 320 mg intervention 2: Oral dose of 300 mg once daily

Protocol document:
Prot_000.pdf: 
3URWRFRO$PHQGPHQW
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO$PHQGPHQW-XO\
3DJHRI
6XPPDU\RI$PHQGHG3URWRFRO&KDQJHV
$3KDVH2SHQODEHO)L[HGVHTXHQFH6WXG\WR,QYHVWLJDWHWKH(IIHFWRIWKH0RGHUDWH
&<3$,QGXFHU5LIDEXWLQRQWKH3KDUPDFRNLQHWLFVRI=DQXEUXWLQLELQ+HDOWK\0DOH
6XEMHFWV
3URWRFRO$PHQGPHQW6WDWXV)LQDO
2ULJLQDO3URWRFRO9HUVLRQ'DWH-XQH
3URWRFRO9HUVLRQ'DWH-XO\
,QYHVWLJDWLRQDO3URGXFW=DQXEUXWLQLE%*%
3URWRFRO5HIHUHQFH1XPEHU%*%
&RYDQFH6WXG\1XPEHU
,1'1XPEHU
6SRQVRU
%HL*HQH/WG
FR%HL*HQH86$,QF
&DPSXV'ULYH6XLWH
6DQ0DWHR&DOLIRUQLD
86$
6WXG\6LWH
&RYDQFH&OLQLFDO5HVHDUFK8QLW,QF
0DVRQ$YHQXH6XLWH
'D\WRQD%HDFK)ORULGD
86$
6SRQVRU6LJQDWRU\

3ULQFLSDO,QYHVWLJDWRU

,QIRUPDWLRQGHVFULEHGKHUHLQLVFRQILGHQWLDODQGPD\EHGLVFORVHGRQO\ZLWKWKHH[SUHVV
ZULWWHQSHUPLVVLRQRIWKH6SRQVRU
BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB
1&7


3URWRFRO$PHQGPHQW
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%

3URWRFRO$PHQGPHQW-XO\
3DJHRI
7KHSULPDU\FKDQJHVLQWKLVDPHQGPHQWDUH
 5HIHUHQFHWRSKDUPDFRJHQHWLFVEORRGVDPSOLQJZDVUHPRYHGIURP$SSHQGL[7RWDO
%ORRG9ROXPHDQG$SSHQGL[6FKHGXOHRI$VVHVVPHQWVDVWKLVLVQRWUHTXLUHGIRUWKLV
VWXG\
0LQRUFKDQJHV
 $SSHQGL[6FKHGXOHRI$VVHVVPHQWIRRWQRWHGHVLJQDWLRQVZHUHXSGDWHGWRDFFRXQWIRU
UHPRYDORIIRRWQRWH³G´ZKLFKZDVSUHYLRXVO\DVVRFLDWHGZLWKSKDUPDFRJHQHWLFVEORRG
VDPSOLQJ
 $SSHQGL[7RWDO%ORRG9ROXPHWRWDOZDVUHGXFHGE\P/GXHWRUHPRYDORI
SKDUPDFRJHQHWLFVEORRGVDPSOLQJIURPWKHWDEOH
 7KHDPHQGPHQWYHUVLRQQXPEHUDQGGDWHZHUHXSGDWHGWKURXJKRXWWKHSURWRFRO


7,7/(3$*(
3URWRFRO
$3KDVH2SHQODEHO)L[HGVHTXHQFH6WXG\WR,QYHVWLJDWHWKH(IIHFWRI
WKH0RGHUDWH&<3$,QGXFHU5LIDEXWLQRQWKH3KDUPDFRNLQHWLFVRI
=DQXEUXWLQLELQ+HDOWK\0DOH6XEMHFWV
3URWRFRO6WDWXV)LQDO
3URWRFRO'DWH-XO\
3URWRFRO9HUVLRQ
,QYHVWLJDWLRQDO0HGLFLQDO3URGXFW=DQXEUXWLQLE%*%

3URWRFRO5HIHUHQFH1XPEHU%*%
&RYDQFH6WXG\1XPEHU
,1'1XPEHU


6SRQVRU
%HL*HQH/WG
FR%HL*HQH86$,QF
&DPSXV'ULYH6XLWH
6DQ0DWHR&DOLIRUQLD
86$
6WXG\6LWH
&RYDQFH&OLQLFDO5HVHDUFK8QLW,QF
0DVRQ$YH6XLWH
'D\WRQD%HDFK)ORULGD
86$


6SRQVRU6LJQDWRU\

3ULQFLSDO,QYHVWLJDWRU




7KLVGRFXPHQWFRQWDLQVFRQILGHQWLDOLQIRUPDWLRQDQGLVWKHSURSULHWDU\SURSHUW\RI%HL*HQH/WG
7KLVGRFXPHQWLVIRUXVHE\LQGLYLGXDOVDQGWKHLUGHVLJQDWHGUHSUHVHQWDWLYHVIRUWKHLUUHYLHZFRQVLGHUDWLRQ
DQGRUSDUWLFLSDWLRQLQLQYHVWLJDWLRQDOWULDOV7KLVGRFXPHQWPD\QRWEHFRSLHGRUGLVWULEXWHGIRUUHYLHZE\
DQ\XQDXWKRUL]HGLQGLYLGXDOVZLWKRXWWKHSULRUZULWWHQDXWKRUL]DWLRQRI%HL*HQH/WG<RXUDFFHSWDQFHRIWKLV
GRFXPHQWFRQVWLWXWHVDJUHHPHQWWKDW\RXZLOOQRWGLVFORVHWKHLQIRUPDWLRQFRQWDLQHGKHUHLQWRRWKHUVZLWKRXW
WKHSULRUZULWWHQDXWKRUL]DWLRQIURP%HL*HQH/WG


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
6321625$33529$/
I have read the protocol “A Phase 1, Open-label, Fixed-sequence Study to Investigate the 
Effect of the Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in 
Healthy Male Subjects” and approve it: 
 
 
 
 
 
 
Date 
BeiGene, Ltd. 
 

	




3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
678'<,'(17,),&$7,21
6SRQVRU
%HL*HQH/WG
FR%HL*HQH86$,QF
&DPSXV'ULYH6XLWH
6DQ0DWHR&$
86$
6SRQVRU¶V6WXG\&RQWDFW

&DPSXV'ULYH6XLWH
6DQ0DWHR&$
86$
7HO

6SRQVRU¶V0HGLFDO&RQWDFW


&DPSXV'ULYH6XLWH
6DQ0DWHR&$
86$
7HO

6WXG\6LWH
&RYDQFH&OLQLFDO5HVHDUFK8QLW,QF
0DVRQ$YHQXH6XLWH
'D\WRQD%HDFK)/
86$
3ULQFLSDO,QYHVWLJDWRU

&RYDQFH&OLQLFDO5HVHDUFK8QLW,QF
0DVRQ$YHQXH6XLWH
'D\WRQD%HDFK)/
86$
7HO

6XELQYHVWLJDWRUV
2EWDLQLQIRUPDWLRQIURP)RUP)'$
&OLQLFDO/DERUDWRU\
/DE&RUS
1RUWK$YHQXH
+ROO\ZRRG)/
86$
%LRDQDO\WLFDO/DERUDWRU\
;HQR%LRWLF/DERUDWRULHV,QF
0RUJDQ/DQH
3ODLQVERUR1-
86$
6WDWLVWLFLDQ

&RYDQFH


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
6<1236,6
7LWOHRIVWXG\$3KDVH2SHQODEHO)L[HGVHTXHQFH6WXG\WR,QYHVWLJDWHWKH(IIHFWRIWKH
0RGHUDWH&<3$,QGXFHU5LIDEXWLQRQWKH3KDUPDFRNLQHWLFVRI=DQXEUXWLQLELQ+HDOWK\0DOH
6XEMHFWV
2EMHFWLYHV
7KHSULPDU\REMHFWLYHRIWKHVWXG\LV
x
WRGHWHUPLQHWKHHIIHFWRIWKHPRGHUDWHF\WRFKURPH3&<3$LQGXFHUULIDEXWLQRQWKH
SKDUPDFRNLQHWLFV3.RI]DQXEUXWLQLELQKHDOWK\PDOHVXEMHFWV
7KHVHFRQGDU\REMHFWLYHRIWKHVWXG\LV
x 
WRHYDOXDWHWKHVDIHW\DQGWROHUDELOLW\RI]DQXEUXWLQLEZKHQFRDGPLQLVWHUHGZLWKULIDEXWLQLQ
KHDOWK\PDOHVXEMHFWV
6WXG\GHVLJQ
7KLVZLOOEHDQRSHQODEHOIL[HGVHTXHQFHVWXG\LQKHDOWK\PDOHVXEMHFWVWRLQYHVWLJDWHWKHHIIHFWRI
&<3$LQGXFWLRQE\VWHDG\VWDWHULIDEXWLQRQWKHVLQJOHGRVH3.RI]DQXEUXWLQLE
3RWHQWLDOVXEMHFWVZLOOEHVFUHHQHGWRDVVHVVWKHLUHOLJLELOLW\WRHQWHUWKHVWXG\ZLWKLQGD\VSULRU
WRWKHILUVWGRVHDGPLQLVWUDWLRQ(OLJLEOHVXEMHFWVZLOOEHDGPLWWHGWRWKHFOLQLFDOUHVHDUFKXQLW
&58RQ'D\
$VLQJOHGRVHDGPLQLVWUDWLRQRI]DQXEUXWLQLERQ'D\ZLOOEHIROORZHGE\DKRXU3.VDPSOH
FROOHFWLRQSHULRGIRUDQDO\VLVRI]DQXEUXWLQLE6XEVHTXHQWO\IROORZLQJULIDEXWLQDGPLQLVWUDWLRQRQ
'D\VWRDVLQJOHGRVHRI]DQXEUXWLQLEZLOOEHFRDGPLQLVWHUHGZLWKULIDEXWLQRQ'D\
IROORZHGE\DKRXU3.VDPSOHFROOHFWLRQSHULRGIRUDQDO\VLVRI]DQXEUXWLQLE6XEMHFWVZLOOEH
FRQILQHGWRWKH&58XQWLOGLVFKDUJHRQ'D\$IROORZXSYLVLWZLOOEHVFKHGXOHGRQ'D\
GD\
1XPEHURIVXEMHFWV
$SSUR[LPDWHO\VXEMHFWVZLOOEHHQUROOHGWRHQVXUHWKDWVXEMHFWVFRPSOHWHWKHVWXG\
'LDJQRVLVDQGPDLQFULWHULDIRULQFOXVLRQ
+HDOWK\PDOHVXEMHFWVDJHGEHWZHHQDQG\HDUVLQFOXVLYHDWVFUHHQLQJZLWKDERG\PDVV
LQGH[EHWZHHQDQGNJPLQFOXVLYHDWVFUHHQLQJ
7HVWSURGXFWVGRVHDQGPRGHRIDGPLQLVWUDWLRQ
x 
6LQJOHGRVHRIPJ]DQXEUXWLQLEJLYHQRUDOO\DVîPJFDSVXOHVLQWKHIDVWHGVWDWHRQ
'D\VDQG
x 
PJULIDEXWLQRQFHGDLO\JLYHQRUDOO\DVîPJFDSVXOHVZLWKIRRGRQ'D\VWRDQG
IDVWHGRQ'D\
'XUDWLRQRIWUHDWPHQW
3ODQQHGVFUHHQLQJGXUDWLRQDSSUR[LPDWHO\ZHHNV
/HQJWKRIFOLQLFFRQILQHPHQW'D\VWR
2XWSDWLHQWIROORZXSYLVLWGD\VGD\DIWHUFOLQLFGLVFKDUJH
3ODQQHGVWXG\GXUDWLRQVFUHHQLQJWRIROORZXSDSSUR[LPDWHO\ZHHNV


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
&ULWHULDIRUHYDOXDWLRQ
3KDUPDFRNLQHWLFV
%ORRGVDPSOHVZLOOEHFROOHFWHGIRUWKHDQDO\VLVRISODVPDFRQFHQWUDWLRQVRI]DQXEUXWLQLEDWWKH
IROORZLQJWLPHSRLQWVUHODWLYHWR]DQXEUXWLQLEGRVLQJSUHGRVHDQG
DQGKRXUVSRVWGRVH7KH3.SDUDPHWHUVRI]DQXEUXWLQLEIROORZLQJ]DQXEUXWLQLEGRVLQJRQ
'D\VDQGZLOOEHFDOFXODWHGXVLQJVWDQGDUGQRQFRPSDUWPHQWDOPHWKRGV7KHIROORZLQJ3.
SDUDPHWHUHQGSRLQWVZLOOEHFDOFXODWHGPD[LPXPREVHUYHGFRQFHQWUDWLRQ&PD[DUHDXQGHUWKH
FRQFHQWUDWLRQWLPHFXUYH$8&IURPWLPH]HURWRWKHWLPHRIWKHODVWTXDQWLILDEOHFRQFHQWUDWLRQ
$8&W$8&IURPWLPH]HURWRLQILQLW\$8&WLPHRIWKHPD[LPXPREVHUYHGFRQFHQWUDWLRQ
7PD[DSSDUHQWWHUPLQDOHOLPLQDWLRQKDOIOLIHWDSSDUHQWRUDOFOHDUDQFH&/)DQGDSSDUHQW
YROXPHRIGLVWULEXWLRQ9])2WKHU3.SDUDPHWHUVPD\EHUHSRUWHG
6DIHW\
6DIHW\HQGSRLQWVIRUWKLVVWXG\LQFOXGHDGYHUVHHYHQWV$(VFOLQLFDOODERUDWRU\HYDOXDWLRQVYLWDO
VLJQDVVHVVPHQWVOHDGHOHFWURFDUGLRJUDPV(&*VDQGSK\VLFDOH[DPLQDWLRQV
6WDWLVWLFDOPHWKRGV
7KHVDPSOHVL]HFKRVHQIRUWKLVVWXG\ZDVEDVHGRQSUHFHGHQWVHWE\RWKHU3.VWXGLHVRIVLPLODU
QDWXUHDQGZDVQRWEDVHGRQSRZHUFDOFXODWLRQV
7KH3.3RSXODWLRQZLOOLQFOXGHDOOVXEMHFWVZKRUHFHLYHGDWOHDVWGRVHRI]DQXEUXWLQLEDQGKDYH
HYDOXDEOH3.GDWDDWOHDVW3.SDUDPHWHUFDQEHFDOFXODWHG$VXEMHFWZLOOEHH[FOXGHGIURPWKH
3.VXPPDU\VWDWLVWLFVDQGVWDWLVWLFDODQDO\VLVLIWKHVXEMHFWKDVDQ$(RIYRPLWLQJWKDWRFFXUVDWRU
EHIRUHîPHGLDQ7PD[
7KH6DIHW\3RSXODWLRQZLOOLQFOXGHDOOVXEMHFWVZKRUHFHLYHGDWOHDVWGRVHRI]DQXEUXWLQLE
7KHSULPDU\3.SDUDPHWHUVDUH$8&W$8&&PD[7PD[W&/)DQG9])IRU]DQXEUXWLQLE
IROORZLQJ]DQXEUXWLQLEGRVLQJRQ'D\VDQG2WKHU3.SDUDPHWHUVPD\EHUHSRUWHGEXWZLOOEH
UHJDUGHGDVVHFRQGDU\DQGZLOOQRWEHVXEMHFWWRLQIHUHQWLDOVWDWLVWLFDODQDO\VLV$OLQHDU
PL[HGPRGHODQDO\VLVZLOOEHDSSOLHGWRDQDO\]HWKHORJWUDQVIRUPHGSULPDU\3.SDUDPHWHUV
$8&W$8&DQG&PD[7KHPRGHODVVXPHVDIL[HGHIIHFWIRUWUHDWPHQWDQGDUDQGRPHIIHFWIRU
VXEMHFW(VWLPDWHVRIJHRPHWULFPHDQUDWLRVWRJHWKHUZLWKWKHFRUUHVSRQGLQJFRQILGHQFH
LQWHUYDOVZLOOEHGHULYHGIRUWKHFRPSDULVRQVRIWKH3.SDUDPHWHUVDVIROORZV
x
]DQXEUXWLQLESOXVULIDEXWLQWHVWYHUVXV]DQXEUXWLQLEDORQHUHIHUHQFH
$OO$(VZLOOEHOLVWHGDQGVXPPDUL]HGXVLQJGHVFULSWLYHPHWKRGRORJ\7KHLQFLGHQFHRI$(VIRU
HDFKWUHDWPHQWZLOOEHSUHVHQWHGE\VHYHULW\DQGE\DVVRFLDWLRQZLWKWKHVWXG\GUXJVDVGHWHUPLQHG
E\WKHLQYHVWLJDWRU(DFK$(ZLOOEHFRGHGXVLQJWKH0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV
2EVHUYHGYDOXHVIRUFOLQLFDOODERUDWRU\HYDOXDWLRQVGDWDOHDG(&*VDQGYLWDOVLJQVZLOOEH
OLVWHGDQGVXPPDUL]HGGHVFULSWLYHO\&OLQLFDOODERUDWRU\GDWDZLWKYDOXHVRXWVLGHRIWKHQRUPDO
UDQJHVZLOOEHLGHQWLILHG2EVHUYHGYDOXHVDQGFKDQJHVIURPEDVHOLQHODERUDWRU\GDWDYLWDOVLJQV
DQG(&*UHVXOWVZLOOEHVXPPDUL]HGE\YLVLW


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
7$%/(2)&217(176
7,7/(3$*( 
6321625$33529$/ 
,19(67,*$725$*5((0(17 
678'<,'(17,),&$7,21 
6<1236,6 
7$%/(2)&217(176 
/,672)7$%/(6$1'),*85(6 
/,672)$%%5(9,$7,216 
 
,1752'8&7,21 
 
2YHUYLHZ 
 
6XPPDU\RI&OLQLFDO([SHULHQFH 
 
6XPPDU\RI6DIHW\LQ+XPDQV 
 
6XPPDU\RI3KDUPDFRNLQHWLFV3KDUPDFRG\QDPLFVDQG3URGXFW
0HWDEROLVPLQ+XPDQV 
 
6WXG\5DWLRQDOH 
 
%HQHILWULVN$VVHVVPHQW 
 
2%-(&7,9(6$1'(1'32,176 
 
2EMHFWLYHV 
 
(QGSRLQWV 
 
3ULPDU\(QGSRLQWV 
 
6HFRQGDU\(QGSRLQWV 
 
,19(67,*$7,21$/3/$1 
 
2YHUDOO6WXG\'HVLJQDQG3ODQ 
 
'LVFXVVLRQRI6WXG\'HVLJQ 
 
,QGXFHU6HOHFWLRQ 
 
6HOHFWLRQRI'RVHVLQWKH6WXG\ 
 
6(/(&7,212)678'<3238/$7,21 
 
,QFOXVLRQ&ULWHULD 
 
([FOXVLRQ&ULWHULD 
 
6XEMHFW1XPEHUDQG,GHQWLILFDWLRQ 
 
6XEMHFW:LWKGUDZDODQG5HSODFHPHQW 
 
6WXG\7HUPLQDWLRQ 
 
678'<75($70(176 
 
'HVFULSWLRQ6WRUDJH3DFNDJLQJDQG/DEHOLQJ 
 
6WXG\7UHDWPHQW$GPLQLVWUDWLRQ 
 
5DQGRPL]DWLRQ 
 
%OLQGLQJ 
 
7UHDWPHQW&RPSOLDQFH 
 
'UXJ$FFRXQWDELOLW\ 


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 
&21&20,7$177+(5$3,(6$1'27+(55(675,&7,216 
 
&RQFRPLWDQW7KHUDSLHV 
 
'LHW 
 
6PRNLQJ 
 
([HUFLVH 
 
%ORRG'RQDWLRQ 
 
&RQWUDFHSWLRQ 
 
678'<$66(660(176$1'352&('85(6 
 
3KDUPDFRNLQHWLF$VVHVVPHQWV 
 
3KDUPDFRNLQHWLF%ORRG6DPSOH&ROOHFWLRQDQG3URFHVVLQJ 
 
$QDO\WLFDO0HWKRGRORJ\ 
 
6DIHW\DQG7ROHUDELOLW\$VVHVVPHQWV 
 
$GYHUVH(YHQWV 
 
&OLQLFDO/DERUDWRU\(YDOXDWLRQV 
 
9LWDO6LJQV 
 
/HDG(OHFWURFDUGLRJUDP 
 
3K\VLFDO([DPLQDWLRQ 
 
6$03/(6,=($1''$7$$1$/<6,6 
 
'HWHUPLQDWLRQRI6DPSOH6L]H 
 
$QDO\VLV3RSXODWLRQV 
 
3KDUPDFRNLQHWLF3RSXODWLRQ 
 
6DIHW\3RSXODWLRQ 
 
3KDUPDFRNLQHWLF$QDO\VHV 
 
6DIHW\$QDO\VLV 
 
,QWHULP$QDO\VLV 
 
5()(5(1&(6 
 $33(1',&(6 
$SSHQGL[$GYHUVH(YHQW5HSRUWLQJ 
 $GYHUVH(YHQWV 
 
'HILQLWLRQDQG5HSRUWLQJRIDQ$GYHUVH(YHQW 
 
$VVHVVPHQWRI6HYHULW\ 
 
$VVHVVPHQWRI&DXVDOLW\ 
 
)ROORZXSRI$GYHUVH(YHQWV 
 
/DERUDWRU\7HVW$EQRUPDOLWLHV 
 'HILQLWLRQRID6HULRXV$GYHUVH(YHQW 
 6XVSHFWHG8QH[SHFWHG6HULRXV$GYHUVH5HDFWLRQ 
 7LPLQJ)UHTXHQF\DQG0HWKRGRI&DSWXULQJ$GYHUVH(YHQWVDQG6HULRXV
$GYHUVH(YHQWV 
 
$GYHUVH(YHQW5HSRUWLQJ3HULRG 
 
(OLFLWLQJ5HVSRQVHV$ERXW$GYHUVH(YHQWV 


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 6SHFLILF,QVWUXFWLRQVIRU5HFRUGLQJ$GYHUVH(YHQWVDQG6HULRXV$GYHUVH
(YHQWV 
 
'HDWK 
 3URPSW5HSRUWLQJRI6HULRXV$GYHUVH(YHQWV 
 
7LPHIUDPHVIRU6XEPLWWLQJ6HULRXV$GYHUVH(YHQWV 
 
&RPSOHWLRQDQG7UDQVPLVVLRQRIWKH6HULRXV$GYHUVH(YHQW5HSRUW 
 
5HJXODWRU\5HSRUWLQJ5HTXLUHPHQWVIRU6HULRXV$GYHUVH(YHQWV 
 3UHJQDQF\5HSRUWLQJ 
 ([SHGLWHG5HSRUWLQJWR+HDOWK$XWKRULWLHV,QYHVWLJDWRUVDQG,QVWLWXWLRQDO
5HYLHZ%RDUGV 
$SSHQGL[&OLQLFDO/DERUDWRU\(YDOXDWLRQV 
$SSHQGL[7RWDO%ORRG9ROXPH 
$SSHQGL[5HJXODWRU\(WKLFDODQG6WXG\2YHUVLJKW&RQVLGHUDWLRQV 
$SSHQGL[6FKHGXOHRI$VVHVVPHQWV 

/,672)7$%/(6$1'),*85(6
7DEOH 
6XPPDU\RI6DIHW\LQ+HDOWK\6XEMHFWV5HFHLYLQJ6LQJOH2UDO'RVHV
RIPJ=DQXEUXWLQLE 
7DEOH 
7LPHIUDPHVDQG'RFXPHQWDWLRQ0HWKRGVIRU5HSRUWLQJ6HULRXV
$GYHUVH(YHQWVWRWKH6SRQVRURU'HVLJQHH 

)LJXUH 
6WXG\6FKHPDWLF 



3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
/,672)$%%5(9,$7,216
$EEUHYLDWLRQ 'HILQLWLRQ
$'/
DFWLYLWLHVRIGDLO\OLYLQJ
$(
DGYHUVHHYHQW
$8&
DUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYH
$8&f
DUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHIURPWLPH]HURWRLQILQLW\
$8&W
DUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHIURPWLPH]HURWRWKHWLPHRIWKH
ODVWTXDQWLILDEOHFRQFHQWUDWLRQ
%7.
%UXWRQ¶VW\URVLQHNLQDVH
&)5
&RGHRI)HGHUDO5HJXODWLRQV
&,206
&RXQFLOIRU,QWHUQDWLRQDO2UJDQL]DWLRQVRI0HGLFDO6FLHQFHV
&/)
DSSDUHQWRUDOFOHDUDQFH
&PD[
PD[LPXPREVHUYHGFRQFHQWUDWLRQ
&52
FRQWUDFWUHVHDUFKRUJDQL]DWLRQ
&58
FOLQLFDOUHVHDUFKXQLW
&7&$(
&RPPRQ7HUPLQRORJ\&ULWHULDIRU$GYHUVH(YHQWV
&<3
F\WRFKURPH3
'',
GUXJGUXJLQWHUDFWLRQ
(&*
HOHFWURFDUGLRJUDP
H&5)
HOHFWURQLFFDVHUHSRUWIRUP
('&
HOHFWURQLFGDWDFDSWXUH
)'$
)RRGDQG'UXJ$GPLQLVWUDWLRQ
*&3
*RRG&OLQLFDO3UDFWLFH
,%
,QYHVWLJDWRU¶V%URFKXUH
,&)
LQIRUPHGFRQVHQWIRUP
,&+
,QWHUQDWLRQDO&RXQFLOIRU&RQIHUHQFHRQ+DUPRQLVDWLRQ
,5%
,QVWLWXWLRQDO5HYLHZ%RDUG
0HG'5$
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV
1&,
1DWLRQDO&DQFHU,QVWLWXWH
3.
SKDUPDFRNLQHWLFV
4'
RQFHGDLO\
47F)
47LQWHUYDOFRUUHFWHGIRUKHDUWUDWHXVLQJ)ULGHULFLD¶VPHWKRG
6$(
VHULRXVDGYHUVHHYHQW
623
VWDQGDUGRSHUDWLQJSURFHGXUHV
W
DSSDUHQWWHUPLQDOHOLPLQDWLRQKDOIOLIH
7PD[
WLPHRIWKHPD[LPXPREVHUYHGFRQFHQWUDWLRQ
8/1
XSSHUOLPLWRIQRUPDO
9])
DSSDUHQWYROXPHRIGLVWULEXWLRQ




3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 ,1752'8&7,21
5HIHUWRWKH=DQXEUXWLQLE,QYHVWLJDWRU¶V%URFKXUH,%IRUGHWDLOHGLQIRUPDWLRQFRQFHUQLQJ
WKHDYDLODEOHSKDUPDFRORJ\WR[LFRORJ\GUXJPHWDEROLVPFOLQLFDOVWXGLHVDQGDGYHUVHHYHQW
$(SURILOHRI]DQXEUXWLQLE
 
2YHUYLHZ
%UXWRQ¶VW\URVLQHNLQDVH%7.LVDVLJQDOLQJPROHFXOHWKDWLVSUHGRPLQDQWO\H[SUHVVHGLQ
%O\PSKRF\WHVDWYDULRXVVWDJHVRIGHYHORSPHQW$FWLYDWLRQRI%7.LQ%FHOOVLQLWLDWHVD
VHULHVRIVLJQDOLQJHYHQWVLQFOXGLQJUHFUXLWPHQWRI%7.WRWKHSODVPDPHPEUDQH
DXWRSKRVSKRU\ODWLRQDWW\URVLQHDFWLYDWLRQRISKRVSKROLSDVH&ȖVXEVHTXHQWQXFOHDU
IDFWRUț%DFWLYDWLRQDQGH[SUHVVLRQRIJHQHVLQYROYHGLQSUROLIHUDWLRQDQGVXUYLYDO
,QKLELWLRQRI%7.KDVHPHUJHGDVDSURPLVLQJVWUDWHJ\IRUWDUJHWLQJ%FHOOPDOLJQDQFLHV
=DQXEUXWLQLE%58.,16$DOVRNQRZQDV%*%D%7.LQKLELWRUKDVEHHQJUDQWHG
DQDFFHOHUDWHGDSSURYDOE\WKH86)RRGDQG'UXJ$GPLQLVWUDWLRQ)'$RQ1RYHPEHU
IRUWKHLQGLFDWLRQRIWUHDWPHQWRIDGXOWSDWLHQWVZLWKPDQWOHFHOOO\PSKRPDZKRKDYH
UHFHLYHGDWOHDVWRQHSULRUWKHUDS\
=DQXEUXWLQLELVDQRYHOVHFRQGJHQHUDWLRQVPDOOPROHFXOHRUDOLQKLELWRURI%7.WKDWZRUNV
E\IRUPLQJDQLUUHYHUVLEOHFRYDOHQWERQGDW&\VZLWKLQWKHDGHQRVLQHWULSKRVSKDWH
ELQGLQJSRFNHWRI%7.=DQXEUXWLQLEKDVEHHQVKRZQWREHPRUHVHOHFWLYHWKDQLEUXWLQLEDQ
DSSURYHGDJHQWIRULQKLELWLRQRI%7.DJDLQVWRIIWDUJHWNLQDVHVLQFOXGLQJ(*)5-$.
+(57(&LQGXFLEOHW\URVLQHNLQDVHDQGRWKHUVEDVHGRQUHVXOWVIURPNLQDVHLQKLELWLRQDQG
FHOOEDVHGDVVD\V7KHLQFUHDVHGVHOHFWLYLW\RI]DQXEUXWLQLEIRU%7.PD\UHVXOWLQDORZHU
LQFLGHQFHDQGVHYHULW\RIRIIWDUJHWWR[LFLWLHVOLQNHGWRLQKLELWLRQRIWKHDIRUHPHQWLRQHG
NLQDVHV=DQXEUXWLQLEZDVVKRZQWREHDWOHDVWIROGZHDNHUWKDQLEUXWLQLELQLQKLELWLQJ
ULWX[LPDELQGXFHGDQWLERG\GHSHQGHQWFHOOPHGLDWHGF\WRWR[LFLW\FRQVLVWHQWZLWKLWVPRUH
VHOHFWLYHDFWLYLW\DJDLQVW%7.DQGZHDNHULQGXFLEOHW\URVLQHNLQDVHLQKLELWRU\DFWLYLW\WKDQ
LEUXWLQLEDVUHYHDOHGLQERWKELRFKHPLFDODQGFHOOXODUDVVD\V
=DQXEUXWLQLELVEHLQJGHYHORSHGE\%HL*HQH/WGDVDVHFRQGJHQHUDWLRQLQKLELWRURI%7.
IRUWKHWUHDWPHQWRI%FHOOPDOLJQDQFLHVLQFOXGLQJPDQWOHFHOOO\PSKRPDFKURQLF
O\PSKRF\WLFOHXNHPLDVPDOOO\PSKRF\WLFO\PSKRPD:DOGHQVWU|P¶VPDFURJOREXOLQHPLD
IROOLFXODUO\PSKRPDPDUJLQDO]RQHO\PSKRPDDQGGLIIXVHODUJH%FHOOO\PSKRPDDVD
PRQRWKHUDS\DQGRULQFRPELQDWLRQZLWKRWKHUDJHQWV=DQXEUXWLQLEHQWHUHGJOREDOFOLQLFDO
GHYHORSPHQWLQ$XJXVWDQGLVEHLQJLQYHVWLJDWHGLQRQJRLQJ3KDVHDQGVWXGLHVLQ
SDWLHQWVZLWK%FHOOPDOLJQDQFLHV
 
6XPPDU\RI&OLQLFDO([SHULHQFH
$VRI$XJXVWFOLQLFDOVWXGLHVLQYHVWLJDWLQJ]DQXEUXWLQLELQSDWLHQWVDUHRQJRLQJ
ZLWKSUHOLPLQDU\UHVXOWVVXPPDUL]HGLQWKH,%
$GGLWLRQDOO\DWRWDORI3KDVHFOLQLFDOSKDUPDFRORJ\VWXGLHVKDYHEHHQFRQGXFWHGDQG
FRPSOHWHG


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 
6XPPDU\RI6DIHW\LQ+XPDQV
6LQJOHGRVHVRIPJ]DQXEUXWLQLEDVGHWDLOHGLQ7DEOHZHUHVDIHDQGZHOOWROHUDWHGLQ
KHDOWK\VXEMHFWV7KHUHVXOWVRIWKHVHVWXGLHVDQGRWKHUFRPSOHWHG3KDVHVWXGLHVDWRWKHU
GRVHOHYHOVRI]DQXEUXWLQLEDUHVXPPDUL]HGLQWKH,%
7DEOH
6XPPDU\RI6DIHW\LQ+HDOWK\6XEMHFWV5HFHLYLQJ6LQJOH2UDO'RVHVRI
PJ=DQXEUXWLQLE
6WXG\
2XWFRPH
6XPPDU\RI6DIHW\
BGB-3111-103, 
Phase 1 food 
effect study 
1RXQH[SHFWHG
VDIHW\LVVXHV
LGHQWLILHG2UDO
GRVHVRIPJ
]DQXEUXWLQLEZHUH
VDIHDQGZHOO
WROHUDWHGLQ
KHDOWK\VXEMHFWV 
2YHUDOO7($(VZHUHUHSRUWHGIRURIVXEMHFWV
0RVWIUHTXHQWO\UHSRUWHG7($(VRIVXEMHFWVRYHUDOOZHUH
KHDGDFKH>@VXEMHFWVO\PSKDGHQRSDWK\>@VXEMHFWV
SKDU\QJLWLVFDWKHWHUVLWHSDLQ(&*47SURORQJHGFRQWXVLRQVNLQ
DEUDVLRQDQGUKLQRUUKRHD>@VXEMHFWVHDFK)RXUWHHQGUXJUHODWHG
7($(VZHUHUHSRUWHGIRUVXEMHFWV,QWKHIDVWHGVWDWHDVHYHUH
7($(S\HORQHSKULWLVZDVUHSRUWHGIRUVXEMHFW
1RGHDWKVRU6$(VZHUHUHSRUWHG7KUHHVXEMHFWVKDG7($(VWKDW
OHGWRGLVFRQWLQXDWLRQRIVWXG\7KH7($(RI(&*47SURORQJHGOHGWR
GLVFRQWLQXDWLRQLQVXEMHFWVERWKDVVHVVHGE\WKHLQYHVWLJDWRUDVQRW
UHODWHGWRVWXG\GUXJDQGWKH7($(RIS\HORQHSKULWLVOHGWR
GLVFRQWLQXDWLRQLQVXEMHFWDVVHVVHGE\WKHLQYHVWLJDWRUDVVHYHUHLQ
LQWHQVLW\DQGUHODWHGWRVWXG\GUXJ 
BGB-3111-104, 
Phase 1 DDI 
study 
6LQJOHGRVHVRI
PJDQG
PJ]DQXEUXWLQLE
DGPLQLVWHUHG
DORQHDQG
FRDGPLQLVWHUHG
ZLWKPJ
ULIDPSLQDQG
PJLWUDFRQD]ROH
UHVSHFWLYHO\ZHUH
VDIHDQGZHOO
WROHUDWHGLQ
KHDOWK\VXEMHFWV
1RQHRIWKHVXEMHFWVGRVHGLQWKHVWXG\UHSRUWHGD7($(KLJKHUWKDQ
*UDGHRUDQ6$(DQGQRVXEMHFWGLVFRQWLQXHGGXHWRD7($(7KH
PDMRULW\RI7($(VZHUHFRQVLGHUHGQRWUHODWHGWRWKHVWXG\GUXJVZHUH
*UDGHLQVHYHULW\DQGUHVROYHGZLWKRXWWUHDWPHQW
1RFOLQLFDOO\VLJQLILFDQWFKDQJHVRUILQGLQJVZHUHQRWHGLQFOLQLFDO
ODERUDWRU\HYDOXDWLRQVYLWDOVLJQVSK\VLFDOH[DPLQDWLRQVRUERG\ZHLJKW
LQWKLVVWXG\1RVXEMHFWKDGD47F)YDOXH!PVHFRUDQLQFUHDVHIURP
EDVHOLQHLQ47F)RI!PVHFGXULQJWKHVWXG\ 
BGB-3111-105, 
Phase 1 AME 
study 
$VLQJOHRUDOGRVH
RIPJRI
]DQXEUXWLQLE
FRQWDLQLQJa
ȝ&LRI
>&@]DQXEUXWLQLE
ZDVZHOOWROHUDWHG
LQKHDOWK\PDOH
VXEMHFWV 
2YHUDOO7($(VZHUHUHSRUWHGIRURIVXEMHFWV
$OO7($(VZHUHPLOGLQVHYHULW\7ZRVXEMHFWVUHSRUWHGDWRWDORI
7($(VWKDWZHUHFRQVLGHUHGWREHSRVVLEO\UHODWHGWRVWXG\GUXJ$OORI
WKHUHPDLQLQJ7($(VZHUHFRQVLGHUHGWREHXQOLNHO\UHODWHGRUQRW
UHODWHGWRVWXG\GUXJ
7KHPRVWIUHTXHQWO\UHSRUWHG7($(VE\62&ZHUH*,GLVRUGHUV
VXEMHFWVUHSRUWHGDWRWDORI7($(VLQWKLV62&7KHVH7($(V
ZHUHDVVHVVHGDVEHLQJXQOLNHO\UHODWHGRUQRWUHODWHGWRVWXG\GUXJ7KH
QH[WPRVWIUHTXHQWO\UHSRUWHG7($(VE\62&ZHUHQHUYRXVV\VWHP
GLVRUGHUVVXEMHFWVUHSRUWHG7($(VRIGL]]LQHVVWKDWZHUH
DVVHVVHGDVEHLQJSRVVLEO\UHODWHGWRVWXG\GUXJ7KHVH7($(VUHVROYHGRQ
WKHVDPHGD\ZLWKRXWFRQFRPLWDQWPHGLFDWLRQ$OORWKHU7($(VLQWKH
VWXG\ZHUHDVVHVVHGDVEHLQJHLWKHUXQOLNHO\UHODWHGWRVWXG\GUXJRUQRW
UHODWHGWRVWXG\GUXJ
$OO7($(VUHVROYHGE\WKHHQGRIWKHVWXG\ZLWKRXWLQWHUYHQWLRQ7KHUH
ZHUHQRGHDWKVRWKHU6$(VRUVHYHUH7($(VUHSRUWHGDQGQRVXEMHFWV
ZLWKGUHZIURPWKHVWXG\EHFDXVHRID7($(
$EEUHYLDWLRQV$0( DEVRUSWLRQPHWDEROLVPDQGH[FUHWLRQ'', GUXJGUXJLQWHUDFWLRQ(&* 
HOHFWURFDUGLRJUDP*, JDVWURLQWHVWLQDO6$( VHULRXVDGYHUVHHYHQW62& V\VWHPRUJDQFODVV7($( 
WUHDWPHQWHPHUJHQWDGYHUVHHYHQW


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 
6XPPDU\RI3KDUPDFRNLQHWLFV3KDUPDFRG\QDPLFVDQG3URGXFW
0HWDEROLVPLQ+XPDQV
=DQXEUXWLQLEZDVUDSLGO\DEVRUEHGDQGHOLPLQDWHGDIWHURUDODGPLQLVWUDWLRQLQKXPDQV
7KHSHDNFRQFHQWUDWLRQVRFFXUUHGDURXQGKRXUVSRVWGRVHDQGWKHPHDQDSSDUHQWWHUPLQDO
HOLPLQDWLRQKDOIOLIHWZDVDSSUR[LPDWHO\WRKRXUV7KHPD[LPXPREVHUYHG
FRQFHQWUDWLRQ&PD[DQGWKHGUXJH[SRVXUHWKHDUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYH
>$8&@LQFUHDVHGLQDQHDUO\GRVHSURSRUWLRQDOPDQQHUIURPPJWRPJERWKDIWHU
VLQJOHGRVHDQGUHSHDWGRVHDGPLQLVWUDWLRQ$IRRGHIIHFWVWXG\%*%LQGLFDWHG
WKDWFRDGPLQLVWUDWLRQZLWKIRRGGLGQRWDSSHDUWRVLJQLILFDQWO\LPSDFWWKHSKDUPDFRNLQHWLFV
3.RI]DQXEUXWLQLE
$KXPDQDEVRUSWLRQPHWDEROLVPH[FUHWLRQVWXG\LQGLFDWHGWKDW]DQXEUXWLQLEZDVSULPDULO\
HOLPLQDWHGE\KHSDWLFPHWDEROLVPDQGIHFDOH[FUHWLRQ$SSUR[LPDWHO\RIWKH
UDGLRODEHOHGGRVHZDVH[FUHWHGLQIHFHVZLWKRQO\RIWKHGRVHH[FUHWHGLQXULQHDV
SDUHQWGUXJ&\WRFKURPH3&<3$LVRHQ]\PHVDUHWKHSULQFLSDOPHWDEROLFSDWKZD\IRU
]DQXEUXWLQLE
$FOLQLFDOGUXJGUXJLQWHUDFWLRQ'',VWXG\ZDVFRQGXFWHGWRDVVHVVWKHSRWHQWLDOLPSDFWRI
&<3$PRGXODWRUVRQWKHH[SRVXUHRI]DQXEUXWLQLELQKHDOWK\YROXQWHHUV%*%
5HVXOWVLQGLFDWHGWKDWFRDGPLQLVWUDWLRQRI]DQXEUXWLQLEZLWKWKHVWURQJ&<3$LQGXFHU
ULIDPSLQPJRQFHGDLO\>4'@GHFUHDVHGH[SRVXUHRI]DQXEUXWLQLELQKHDOWK\YROXQWHHUV
E\IROGIRU$8&IURPWLPH]HURWRLQILQLW\$8&DQGIROGIRU&PD[
&RDGPLQLVWUDWLRQRI]DQXEUXWLQLEZLWKWKHVWURQJ&<3$LQKLELWRULWUDFRQD]ROHPJ4'
LQFUHDVHGH[SRVXUHRI]DQXEUXWLQLEE\IROGIRU$8&DQGE\IROGIRU&PD[7KHVH
UHVXOWVDUHFRQVLVWHQWZLWKWKHUROHIRU&<3$LVRHQ]\PHVDVWKHSULQFLSDOPHWDEROLFSDWKZD\
IRU]DQXEUXWLQLE$GGLWLRQDOO\DSK\VLRORJLFDOO\EDVHG3.PRGHOZDVGHYHORSHGDQGZDV
XVHGWRSUHGLFWWKHHIIHFWRI&<3$LQKLELWRUVDQG&<3$LQGXFHUVRQWKH3.RI
]DQXEUXWLQLE3K\VLRORJLFDOO\EDVHG3.VLPXODWLRQVVXJJHVWWKDWFRDGPLQLVWUDWLRQRIPXOWLSOH
GRVHVRIDPRGHUDWH&<3$LQKLELWRUHJIOXFRQD]ROHGLOWLD]HPDQGHU\WKURP\FLQPD\
LQFUHDVHWKH&PD[DQG$8&RI]DQXEUXWLQLEE\DSSUR[LPDWHO\IROG([SRVXUHLQFUHDVHVZHUH
OHVVWKDQIROGZLWKDPLOG&<3$LQKLELWRU3K\VLRORJLFDOO\EDVHG3.VLPXODWLRQV
VXJJHVWWKDWDPRGHUDWH&<3$LQGXFHUHJHIDYLUHQ]PD\GHFUHDVHWKH&PD[DQG$8&RI
]DQXEUXWLQLEE\DSSUR[LPDWHO\WRIROG$FOLQLFDO'',VWXG\%*%VKRZHG
WKDW]DQXEUXWLQLEKDGQRHIIHFWRQD&<3&VXEVWUDWHZDUIDULQDQGDEUHDVWFDQFHU
UHVLVWDQFHSURWHLQVXEVWUDWHURVXYDVWDWLQ=DQXEUXWLQLELVDPLOG&<3$DQG&<3&
LQGXFHU
$GHGLFDWHGKHSDWLFLPSDLUPHQWVWXG\%*%VKRZHGWKDWWKHUHZDVQRVXEVWDQWLDO
GLIIHUHQFHLQ3.EHWZHHQSDWLHQWVZLWKPLOGPRGHUDWHKHSDWLFLPSDLUPHQWDQGKHDOWK\
VXEMHFWV7KHWRWDODQGXQERXQG$8&RI]DQXEUXWLQLELQVXEMHFWVZLWKVHYHUHKHSDWLF
LPSDLUPHQWZHUHDQGIROGUHVSHFWLYHO\RIWKRVHLQKHDOWK\FRQWUROV
 
6WXG\5DWLRQDOH
*LYHQWKHGHFUHDVHGH[SRVXUHRIDSSUR[LPDWHO\IROGIRU]DQXEUXWLQLEZKHQDGPLQLVWHUHG
ZLWKDVWURQJ&<3$LQGXFHUULIDPSLQDVGHWHUPLQHGLQVWXG\%*%DFOLQLFDO
'',VWXG\LVZDUUDQWHGWRGHWHUPLQHWKHH[WHQWRILQWHUDFWLRQZLWKPRGHUDWH&<3$
LQGXFHUV$PRQJWKHUHFRPPHQGHGPRGHUDWH&<3$LQGXFHUVIRU'',HYDOXDWLRQULIDEXWLQ


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
ZDVVHOHFWHGLQWKLVVWXG\DVLWLVPRUHFOLQLFDOO\UHOHYDQWLQWKHWDUJHWSDWLHQWSRSXODWLRQRI
]DQXEUXWLQLE7KHUHKDYHEHHQFDVHVLQ]DQXEUXWLQLEFOLQLFDOWULDOVZKHUHSUHVFULELQJRIDQ
DQWLWXEHUFXORVLVDJHQWVXFKDVULIDPSLQRUULIDEXWLQZDVZDUUDQWHG5LIDEXWLQLVDILUVWOLQH
WKHUDSHXWLFDOWHUQDWLYHWRULIDPSLQLHGXHWRLQWROHUDQFHWRRUXQDFFHSWDEOHGUXJLQWHUDFWLRQV
ZLWKPHGLFDWLRQFRDGPLQLVWHUHGZLWKULIDPSLQLQWKHWUHDWPHQWRIGUXJVHQVLWLYH
WXEHUFXORVLV:LWKULIDPSLQEHLQJDSRWHQW&<3$LQGXFHUWKDWVKRXOGEHDYRLGHGGXULQJ
FRDGPLQLVWUDWLRQRI]DQXEUXWLQLEHYDOXDWLQJWKH3.RI]DQXEUXWLQLEFRDGPLQLVWHUHGZLWK
ULIDEXWLQZRXOGEHFOLQLFDOO\PHDQLQJIXO)XUWKHUPRUHVLQFH+,9SDWLHQWVDUHH[FOXGHGIURP
]DQXEUXWLQLEFOLQLFDOWULDOVVWXGLHVZLWKPRGHUDWH&<3$LQGXFHUVVXFKDVHIDYLUHQ]DQG
HWUDYLULQHIRUWKHWUHDWPHQWRI+,9LQIHFWLRQZRXOGQRWEHDVLQIRUPDWLYH5HVXOWVIURPWKLV
VWXG\FRXOGEHXVHGWRGLUHFWO\LPSDFWGRVHDGMXVWPHQWUHFRPPHQGDWLRQLQRQJRLQJ
]DQXEUXWLQLEVWXGLHVDQGWRVXSSRUWGRVHUHFRPPHQGDWLRQZKHQ]DQXEUXWLQLELV
FRDGPLQLVWHUHGZLWKGUXJVWKDWDUHPRGHUDWH&<3$LQGXFHUV
 
%HQHILWULVN$VVHVVPHQW
+HDOWK\VXEMHFWVLQWKHFXUUHQWVWXG\ZLOOQRWUHFHLYHDQ\KHDOWKEHQHILWEH\RQGWKDWRIDQ
DVVHVVPHQWRIWKHLUPHGLFDOVWDWXVIURPSDUWLFLSDWLQJLQWKHVWXG\7KHULVNVRISDUWLFLSDWLRQ
DUHSULPDULO\WKRVHDVVRFLDWHGZLWKDGYHUVHUHDFWLRQVWRWKHVWXG\WUHDWPHQWVDOWKRXJKWKHUH
PD\DOVREHVRPHGLVFRPIRUWIURPFROOHFWLRQRIEORRGVDPSOHVDQGRWKHUVWXG\SURFHGXUHV
0RUHLQIRUPDWLRQDERXWWKHNQRZQDQGH[SHFWHGEHQHILWVULVNVDQGUHDVRQDEO\DQWLFLSDWHG
$(VDVVRFLDWHGZLWK]DQXEUXWLQLEPD\EHIRXQGLQWKH,%
0RUHLQIRUPDWLRQDERXWWKHNQRZQDQGH[SHFWHGEHQHILWVDQGULVNVRIULIDEXWLQPD\EHIRXQG
LQWKHSUHVFULELQJLQIRUPDWLRQ


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 2%-(&7,9(6$1'(1'32,176
 
2EMHFWLYHV
7KHSULPDU\REMHFWLYHRIWKHVWXG\LV
x WRGHWHUPLQHWKHHIIHFWRIWKHPRGHUDWH&<3$LQGXFHUULIDEXWLQRQWKH3.RI
]DQXEUXWLQLELQKHDOWK\PDOHVXEMHFWV
7KHVHFRQGDU\REMHFWLYHRIWKHVWXG\LV
x WRHYDOXDWHWKHVDIHW\DQGWROHUDELOLW\RI]DQXEUXWLQLEZKHQFRDGPLQLVWHUHGZLWK
ULIDEXWLQLQKHDOWK\PDOHVXEMHFWV
 
(QGSRLQWV
 
3ULPDU\(QGSRLQWV
7KH3.RXWFRPHHQGSRLQWVRI]DQXEUXWLQLEGHULYHGIURPWKHSODVPDFRQFHQWUDWLRQWLPH
SURILOHVIROORZLQJRUDODGPLQLVWUDWLRQRI]DQXEUXWLQLERQ'D\VDQGDUHDVIROORZV
x $8&IURPWLPH]HURWRWKHWLPHRIWKHODVWTXDQWLILDEOHFRQFHQWUDWLRQ$8&W
x $8&
x &PD[
x WLPHRIWKHPD[LPXPREVHUYHGFRQFHQWUDWLRQ7PD[
x W
x DSSDUHQWRUDOFOHDUDQFH&/)
x DSSDUHQWYROXPHRIGLVWULEXWLRQ9])
2WKHU3.SDUDPHWHUVPD\DOVREHUHSRUWHG
 
6HFRQGDU\(QGSRLQWV
7KHVDIHW\RXWFRPHPHDVXUHVIRUWKLVVWXG\DUHDVIROORZV
x LQFLGHQFHDQGVHYHULW\RI$(V
x LQFLGHQFHRIODERUDWRU\DEQRUPDOLWLHVEDVHGRQKHPDWRORJ\FOLQLFDOFKHPLVWU\DQG
XULQDO\VLVWHVWUHVXOWV
x YLWDOVLJQPHDVXUHPHQWV
x OHDGHOHFWURFDUGLRJUDP(&*SDUDPHWHUV
x SK\VLFDOH[DPLQDWLRQV


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 ,19(67,*$7,21$/3/$1

2YHUDOO6WXG\'HVLJQDQG3ODQ
7KLVZLOOEHDQRSHQODEHOIL[HGVHTXHQFHVWXG\LQKHDOWK\PDOHVXEMHFWVWRLQYHVWLJDWHWKH
HIIHFWRI&<3$LQGXFWLRQE\VWHDG\VWDWHULIDEXWLQRQWKHVLQJOHGRVH3.RI]DQXEUXWLQLE
$SSUR[LPDWHO\VXEMHFWVZLOOEHHQUROOHGWRHQVXUHWKDWVXEMHFWVFRPSOHWHWKHVWXG\
3RWHQWLDOVXEMHFWVZLOOEHVFUHHQHGWRDVVHVVWKHLUHOLJLELOLW\WRHQWHUWKHVWXG\ZLWKLQGD\V
SULRUWRWKHILUVWGRVHDGPLQLVWUDWLRQ(OLJLEOHVXEMHFWVZLOOEHDGPLWWHGWRWKHFOLQLFDOUHVHDUFK
XQLW&58RQ'D\$OOVXEMHFWVZLOO UHFHLYHWKHIROORZLQJWUHDWPHQWV
x
'D\VLQJOHRUDOGRVHRIPJ]DQXEUXWLQLEDIWHURYHUQLJKWIDVWRIWRKRXUV
x
'D\VWRRUDOGRVHRIPJULIDEXWLQ4'ZLWKIRRGVWDQGDUGPHDO
x
'D\VLQJOHRUDOGRVHRIPJ]DQXEUXWLQLEDQG4'GRVHRIPJULIDEXWLQ
DIWHURYHUQLJKWIDVWRIWRKRXUV
2Q'D\VDQGVHULDOEORRGFROOHFWLRQVZLOOEHREWDLQHGIURPSUHGRVHWKURXJKKRXUV
SRVWGRVHIRUDQDO\VLVRISODVPDFRQFHQWUDWLRQVRI]DQXEUXWLQLEDQGPHWDEROLWHVLI
DSSOLFDEOH$6FKHGXOHRI$VVHVVPHQWVLVSUHVHQWHGLQ$SSHQGL[
6XEMHFWVZLOOEHFRQILQHGWRWKH&58XQWLOGLVFKDUJHRQ'D\$IROORZXSYLVLWZLOOEH
VFKHGXOHGRQ'D\GD\$VXEMHFWZLOOEHFRQVLGHUHGWRKDYHFRPSOHWHGWKHVWXG\
ZKHQWKH\KDYHSDUWLFLSDWHGLQWKHIROORZXSYLVLW
$QRYHUYLHZRIWKHVWXG\GHVLJQLVVKRZQLQ)LJXUH
)LJXUH
6WXG\6FKHPDWLF
7KH PD[LPXPWRWDOGXUDWLRQRIVWXG\SDUWLFLSDWLRQIRUHDFKVXEMHFWIURPVFUHHQLQJWKURXJK
IROORZXSYLVLWLVDQWLFLSDWHGWREHDSSUR[LPDWHO\ZHHNV
7KHVWDUWRIWKHVWXG\LVGHILQHGDVWKHGDWHWKHILUVWVXEMHFWVLJQVDQLQIRUPHGFRQVHQWIRUP
,&)7KHSRLQWRIHQUROOPHQWRFFXUVDWWKHWLPHRIVXEMHFWQXPEHUDOORFDWLRQ7KHHQGRIWKH
VWXG\LVGHILQHGDVWKHGDWHRIWKHODVWVXEMHFW¶VODVWDVVHVVPHQWVFKHGXOHGRUXQVFKHGXOHG


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
$6FKHGXOHRI$VVHVVPHQWVLVSUHVHQWHGLQ$SSHQGL[
 
'LVFXVVLRQRI6WXG\'HVLJQ
7KLVVWXG\LVGHVLJQHGWRHYDOXDWHWKHHIIHFWRIULIDEXWLQDPRGHUDWH&<3$LQGXFHURQWKH
3.RI]DQXEUXWLQLELQKHDOWK\VXEMHFWV7KHIL[HGVHTXHQFHGHVLJQXVHGLQWKLVVWXG\LV
W\SLFDOIRULQWHUDFWLRQVWXGLHVZKHUHDUHODWLYHO\VPDOOQXPEHURIVXEMHFWVDUHUHTXLUHG
EHFDXVHLWDOORZVLQWUDVXEMHFWFRPSDULVRQVDQGUHGXFHVLQWHUVXEMHFWYDULDELOLW\7KLVVWXG\
ZLOOEHRSHQODEHODVWKHVWXG\HQGSRLQWVDUHREMHFWLYHUDWKHUWKDQVXEMHFWLYHWKHUHIRUH
LQYHVWLJDWRUVDQGVXEMHFWVGRQRWQHHGWREHEOLQGHG
&RQGXFWLQJWKHVWXG\LQKHDOWK\VXEMHFWVPLWLJDWHVWKHSRWHQWLDOFRQIRXQGLQJHIIHFWVRIWKH
GLVHDVHVWDWHDQGFRQFRPLWDQWPHGLFDWLRQV
 
,QGXFHU6HOHFWLRQ
5LIDEXWLQKDVEHHQXVHGDVDPRGHUDWH&<3$LQGXFHULQFOLQLFDO'',VWXGLHV5LIDEXWLQ
LVDQDQWLEDFWHULDODJHQWWKDWLVLQGLFDWHGLQWKHWUHDWPHQWRIP\FREDFWHULDOLQIHFWLRQVDQGLWV
DFWLYHPHWDEROLWH2GHVDFHW\OULIDEXWLQFRQWULEXWHVWRHTXLYDOHQWDQWLPLFURELDODFWLYLW\RI
WKHSDUHQWGUXJ,WLVSULPDULO\PHWDEROL]HGE\&<3$HQ]\PHVDQGPXOWLSOHGRVLQJRI
ULIDEXWLQZDVDVVRFLDWHGZLWKLQGXFWLRQRIHQ]\PHVRIWKH&<3$VXEIDPLO\)ROORZLQJD
VLQJOHRUDOGRVHRIPJULIDEXWLQZDVUHDGLO\DEVRUEHGZLWK7PD[UDQJHRIWRKRXUV
5LIDEXWLQZDVVORZO\HOLPLQDWHGIURPSODVPDZLWKDPHDQWRIKRXUVUDQJH
WRKRXUV$OWKRXJKWKHV\VWHPLFOHYHOVRIULIDEXWLQIROORZLQJPXOWLSOHGRVLQJ
GHFUHDVHGE\LWVWUHPDLQHGXQFKDQJHG
5LIDEXWLQZDVIRXQGWRKDYHDZHDNLQGXFWLRQSRWHQWLDOWRZDUGV&<3&EXWZDVQRWDQ
LQGXFHURI3JO\FRSURWHLQRURUJDQLFDQLRQWUDQVSRUWLQJSRO\SHSWLGH0HWDEROLFLQGXFWLRQRI
&<3$HQ]\PHVDUHH[SHFWHGWRUHVXOWLQGHFUHDVHGSODVPDFRQFHQWUDWLRQVRIFRDGPLQLVWHUHG
GUXJVWKDWDUHSULPDULO\VXEVWUDWHVRIDQGPHWDEROL]HGE\&<3$HQ]\PHVVXFKDV
]DQXEUXWLQLE
5LIDEXWLQZDVVHOHFWHGLQWKLVVWXG\DVLWLVPRUHFOLQLFDOO\UHOHYDQWLQWKHWDUJHWSDWLHQW
SRSXODWLRQRI]DQXEUXWLQLELHNQRZQPRGHUDWH&<3$LQGXFHUVVXFKDVHIDYLUHQ]DQG
HWUDYLULQHDUHLQGLFDWHGIRUWUHDWPHQWRI+,9LQIHFWLRQDQG+,9SDWLHQWVDUHH[FOXGHGIURP
]DQXEUXWLQLEFOLQLFDOWULDOV5LIDEXWLQLVDILUVWOLQHWKHUDSHXWLFDOWHUQDWLYHWRULIDPSLQLHGXH
WRLQWROHUDQFHWRRUXQDFFHSWDEOHLQWHUDFWLRQVZLWKPHGLFDWLRQFRDGPLQLVWHUHGZLWKULIDPSLQ
LQWKHWUHDWPHQWRIGUXJVHQVLWLYHWXEHUFXORVLV:LWKULIDPSLQEHLQJDSRWHQW&<3$
LQGXFHUHYDOXDWLQJWKH3.RI]DQXEUXWLQLEFRDGPLQLVWHUHGZLWKULIDEXWLQZRXOGEH
PHDQLQJIXOWRGHWHUPLQHLIGRVHDGMXVWPHQWVVKRXOGEHFRQVLGHUHGZKHQ]DQXEUXWLQLELV
FRDGPLQLVWHUHGZLWKGUXJVWKDWDUHPRGHUDWH&<3$LQGXFHUV
 
6HOHFWLRQRI'RVHVLQWKH6WXG\
$GRVHRIPJ]DQXEUXWLQLEZKLFKZDVDOVRDGPLQLVWHUHGLQWKHULIDPSLQ'',VWXG\
%*%KDVEHHQFKRVHQIRUWKLVVWXG\WRSURYLGHDGLUHFWFRPSDULVRQRIWKHHIIHFW
RIVWURQJYHUVXVPRGHUDWH&<3$LQGXFWLRQ$GRVHRIPJ4'ZDVDGPLQLVWHUHGWR
SDWLHQWVLQ3KDVHVWXG\%*%$8DQGZDVZHOOWROHUDWHG$VLQJOHGRVHRI
PJZDVDOVRDGPLQLVWHUHGWRKHDOWK\VXEMHFWVLQWKHGHGLFDWHGIRRGHIIHFWVWXG\


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
%*%DQGDEVRUSWLRQPHWDEROLVPDQGH[FUHWLRQVWXG\%*%DQGKDV
EHHQVKRZQWREHVDIHDQGZHOOWROHUDWHGLQWKHVHVWXGLHV
*LYHQWKHREMHFWLYHRIGHWHUPLQLQJZKHWKHUDPRGHUDWH&<3$LQGXFHUKDVDQHIIHFWRQWKH
]DQXEUXWLQLE3.WKLVGRVHLVFRQVLGHUHGWREHDGHTXDWHWRDFKLHYHVWXG\REMHFWLYHVZLWK
PLQLPDOULVNWRVXEMHFWV
$VSHU)'$JXLGDQFHIRU'',VWXGLHVDVLQJOHGRVHVWXG\GHVLJQLVEHLQJXVHGDV
]DQXEUXWLQLE3.LQWKHFOLQLFDOO\UHOHYDQWGRVHUDQJHLVOLQHDUZLWKVLQJOHGRVH3.DOORZLQJ
SUHGLFWLRQRIPXOWLSOHGRVH3.
&OLQLFDOO\UHFRPPHQGHGGRVHVRIULIDEXWLQPJ4'ZLOOEHXVHGGXULQJWKLVVWXG\
5LIDEXWLQZLOOEHDGPLQLVWHUHG4'IRUGD\VSULRUWRFRDGPLQLVWUDWLRQZLWK]DQXEUXWLQLELQ
RUGHUWRDFKLHYHVWDEOHLQGXFWLRQRI&<3$
 6(/(&7,212)678'<3238/$7,21
 
,QFOXVLRQ&ULWHULD
6XEMHFWVPXVWVDWLVI\DOORIWKHIROORZLQJFULWHULDDWWKHVFUHHQLQJYLVLWXQOHVVRWKHUZLVH
VWDWHG
 0DOHVRIDQ\UDFHEHWZHHQDQG\HDUVRIDJHLQFOXVLYH
 %RG\PDVVLQGH[EHWZHHQDQGNJPLQFOXVLYH
 ,QJRRGKHDOWKGHWHUPLQHGE\QRFOLQLFDOO\VLJQLILFDQWILQGLQJVIURPPHGLFDOKLVWRU\
SK\VLFDOH[DPLQDWLRQOHDG(&*VYLWDOVLJQPHDVXUHPHQWVDQGFOLQLFDOODERUDWRU\
HYDOXDWLRQVFRQJHQLWDOQRQKHPRO\WLFK\SHUELOLUXELQHPLD>HJ*LOEHUW¶VV\QGURPH@LV
QRWDFFHSWDEOHDWVFUHHQLQJRUFKHFNLQDVDVVHVVHGE\WKHLQYHVWLJDWRURUGHVLJQHH
 0DOHVXEMHFWVDUHHOLJLEOHLIYDVHFWRPL]HGRULIWKH\DJUHHWRWKHXVHRIEDUULHU
FRQWUDFHSWLRQZLWKRWKHUKLJKO\HIIHFWLYHPHWKRGVGHVFULEHGLQ6HFWLRQGXULQJ
WKHVWXG\WUHDWPHQWSHULRGDQGIRUGD\VDIWHUWKHODVWGRVHRI]DQXEUXWLQLE0DOHV
ZLOODOVRDJUHHWRUHIUDLQIURPGRQDWLQJVSHUPIURPWKHWLPHRIWKHILUVWGRVHRI
]DQXEUXWLQLEXQWLOGD\VDIWHUWKHODVWGRVHRI]DQXEUXWLQLE
 $EOHWRFRPSUHKHQGDQGZLOOLQJWRVLJQDQ,&)DQGWRDELGHE\WKHVWXG\UHVWULFWLRQV
 
([FOXVLRQ&ULWHULD
6XEMHFWVZLOOEHH[FOXGHGIURPWKHVWXG\LIWKH\VDWLVI\DQ\RIWKHIROORZLQJFULWHULD
 6LJQLILFDQWKLVWRU\RUFOLQLFDOPDQLIHVWDWLRQRIDQ\PHWDEROLFDOOHUJLFGHUPDWRORJLFDO
KHSDWLFUHQDOKHPDWRORJLFDOSXOPRQDU\FDUGLRYDVFXODUJDVWURLQWHVWLQDO
QHXURORJLFDOUHVSLUDWRU\HQGRFULQHRUSV\FKLDWULFGLVRUGHUWKDWLQWKHLQYHVWLJDWRU¶V
MXGJPHQWFRXOGLQWHUIHUHZLWKWKHLQWHUSUHWDWLRQRIWKHVWXG\UHVXOWV
 (YLGHQFHRIDQ\LQIHFWLRQVEDFWHULDOYLUDOIXQJDOSDUDVLWLFZLWKLQZHHNVSULRUWR
WKHILUVWGRVHRIVWXG\GUXJDVGHWHUPLQHGE\WKHLQYHVWLJDWRURUGHVLJQHH
 +LVWRU\RIVLJQLILFDQWK\SHUVHQVLWLYLW\LQWROHUDQFHRUDOOHUJ\WRDQ\GUXJFRPSRXQG
IRRGRURWKHUVXEVWDQFHXQOHVVDSSURYHGE\WKHLQYHVWLJDWRURUGHVLJQHH


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 +LVWRU\RIVWRPDFKRULQWHVWLQDOVXUJHU\RUUHVHFWLRQWKDWZRXOGSRWHQWLDOO\DOWHU
DEVRUSWLRQDQGRUH[FUHWLRQRIRUDOO\DGPLQLVWHUHGGUXJVDSSHQGHFWRP\DQGKHUQLD
UHSDLUZLOOEHDOORZHG
 ,QDELOLW\WRVZDOORZFDSVXOHV
 +LVWRU\RUSUHVHQFHRIDQDEQRUPDO(&*SULRUWRWKHILUVWGRVHRIWKHVWXG\GUXJWKDW
LQWKHRSLQLRQRIWKHLQYHVWLJDWRURUGHVLJQHHLVFOLQLFDOO\VLJQLILFDQW
 +LVWRU\RISURORQJHG47LQWHUYDO47LQWHUYDOFRUUHFWHGIRUKHDUWUDWHZLWK47
LQWHUYDOFRUUHFWHGIRUKHDUWUDWHXVLQJ)ULGHULFLD¶VPHWKRG47F)!PVHF
 +LVWRU\RUSUHVHQFHRIDWULDOILEULOODWLRQRURWKHUVLJQLILFDQWDUUK\WKPLD
 $EQRUPDOOLYHUIXQFWLRQWHVWVDVGHILQHGE\DVSDUWDWHDPLQRWUDQVIHUDVHDODQLQH
DPLQRWUDQVIHUDVHRUWRWDOELOLUXELQ!îXSSHUOLPLWRIQRUPDO8/1UDQJH
FRQILUPHGE\UHSHDWDWVFUHHQLQJRUFKHFNLQ
 :KLWHEORRGFHOOFRXQWQHXWURSKLOFRXQWO\PSKRF\WHRUSODWHOHWFRXQWEHORZWKH
ORZHUOLPLWRIQRUPDORUKHPRJORELQJG/FRQILUPHGE\UHSHDWDWVFUHHQLQJRU
FKHFNLQ
 /LSDVHYDOXH!î8/1FRQILUPHGE\UHSHDWDWVFUHHQLQJRUFKHFNLQ
 (VWLPDWHGJORPHUXODUILOWUDWLRQUDWHP/PLQPDWVFUHHQLQJGHWHUPLQHGE\
XVHRIWKH0RGLILFDWLRQRI'LHWLQ5HQDO'LVHDVHHTXDWLRQ
 +LVWRU\RIDOFRKROLVPRUGUXJFKHPLFDODEXVHZLWKLQ\HDUSULRUWRFKHFNLQ
 3RVLWLYHXULQHGUXJVFUHHQDWVFUHHQLQJRUFKHFNLQRUSRVLWLYHDOFRKROWHVWUHVXOWDW
FKHFNLQ
 3RVLWLYHKHSDWLWLVSDQHODQGRUSRVLWLYH+,9WHVW$SSHQGL[6XEMHFWVZKRVH
KHSDWLWLVSDQHOUHVXOWVDUHFRPSDWLEOHZLWKSULRULPPXQL]DWLRQDQGQRWLQIHFWLRQPD\
EHLQFOXGHGDWWKHGLVFUHWLRQRIWKHLQYHVWLJDWRU
 3DUWLFLSDWLRQLQDFOLQLFDOVWXG\LQYROYLQJDGPLQLVWUDWLRQRIDQLQYHVWLJDWLRQDOGUXJ
QHZFKHPLFDOHQWLW\RUXVHRIDQH[SHULPHQWDOPHGLFDOGHYLFHLQWKHSDVWGD\VRU
KDOIOLYHVZKLFKHYHULVORQJHUSULRUWRFKHFNLQ
 8VHRULQWHQGHGXVHRIDQ\PHGLFDWLRQVSURGXFWVNQRZQWRDOWHUGUXJDEVRUSWLRQ
PHWDEROLVPRUHOLPLQDWLRQSURFHVVHVLQFOXGLQJ6W-RKQ¶V:RUWZLWKLQGD\VSULRU
WRFKHFNLQXQOHVVGHHPHGDFFHSWDEOHE\WKHLQYHVWLJDWRURUGHVLJQHH
 8VHRULQWHQGHGXVHRIDQ\SUHVFULSWLRQPHGLFDWLRQVSURGXFWVLQFOXGLQJRUDO
LPSODQWDEOHWUDQVGHUPDOLQMHFWDEOHRULQWUDXWHULQHKRUPRQDOFRQWUDFHSWLYHVZLWKLQ
GD\VSULRUWRFKHFNLQXQOHVVGHHPHGDFFHSWDEOHE\WKHLQYHVWLJDWRURUGHVLJQHH
 8VHRULQWHQGHGXVHRIVORZUHOHDVHPHGLFDWLRQVSURGXFWVFRQVLGHUHGWRVWLOOEHDFWLYH
ZLWKLQGD\VSULRUWRFKHFNLQXQOHVVGHHPHGDFFHSWDEOHE\WKHLQYHVWLJDWRURU
GHVLJQHH
 8VHRULQWHQGHGXVHRIDQ\QRQSUHVFULSWLRQPHGLFDWLRQVSURGXFWVLQFOXGLQJYLWDPLQV
PLQHUDOVDQGSK\WRWKHUDSHXWLFKHUEDOSODQWGHULYHGSUHSDUDWLRQVZLWKLQGD\VSULRU
WRFKHFNLQXQOHVVGHHPHGDFFHSWDEOHE\WKHLQYHVWLJDWRURUGHVLJQHH


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 5HFHLSWRULQWHQGHGUHFHLSWRIDQ\OLYHYDFFLQHZLWKLQZHHNVSULRUWRWKHILUVWGRVH
RIVWXG\GUXJRURWKHUQRQOLYHYDFFLQHZLWKLQGD\VSULRUWRWKHILUVWGRVHRIVWXG\
GUXJ
 8VHRIWREDFFRRUQLFRWLQHFRQWDLQLQJSURGXFWVZLWKLQPRQWKVSULRUWRFKHFNLQ
 5HFHLSWRIEORRGSURGXFWVZLWKLQPRQWKVSULRUWRFKHFNLQ
 'RQDWLRQRIEORRGIURPZHHNVSULRUWRVFUHHQLQJSODVPDIURPZHHNVSULRUWR
VFUHHQLQJRUSODWHOHWVIURPZHHNVSULRUWRVFUHHQLQJ
 3RRUSHULSKHUDOYHQRXVDFFHVV
 0DMRUVXUJLFDOSURFHGXUHRUVLJQLILFDQWWUDXPDWLFLQMXU\ZLWKLQGD\VSULRUWR
FKHFNLQRUDQWLFLSDWLRQRIWKHQHHGIRUPDMRUVXUJHU\GXULQJWKHVWXG\
 ,QDELOLW\WRUHVLGHDWWKH&58DQGRULQDELOLW\WREHDYDLODEOHIRUSURWRFROUHTXLUHG
SURFHGXUHVRUIROORZXSDVVHVVPHQWV
 $Q\RWKHUXQVSHFLILHGUHDVRQWKDWLQWKHRSLQLRQRIWKHLQYHVWLJDWRURUGHVLJQHHRU
VSRQVRUZRXOGPDNHWKHVXEMHFWXQVXLWDEOHIRUHQUROOPHQW
 
6XEMHFW1XPEHUDQG,GHQWLILFDWLRQ
6XEMHFWVZLOOKDYHDXQLTXHLGHQWLILFDWLRQQXPEHUXVHGDWVFUHHQLQJ6XEMHFWVZLOOEHDVVLJQHG
DVXEMHFWQXPEHUSULRUWRWKHILUVWGRVLQJRFFDVLRQ$VVLJQPHQWRIVXEMHFWQXPEHUVZLOOEHLQ
DVFHQGLQJRUGHUDQGQRQXPEHUVZLOOEHRPLWWHGHJ6XEMHFWV
5HSODFHPHQWVXEMHFWV6HFWLRQZLOOEHDVVLJQHGDVXEMHFWQXPEHUFRUUHVSRQGLQJWRWKH
QXPEHURIWKHVXEMHFWKHLVUHSODFLQJSOXVHJ6XEMHFWUHSODFHV6XEMHFW
6XEMHFWVZLOOEHLGHQWLILHGE\VFUHHQLQJLGHQWLILFDWLRQQXPEHURUVXEMHFWQXPEHURQO\RQDOO
VWXG\GRFXPHQWDWLRQ$OLVWLGHQWLI\LQJWKHVXEMHFWVE\VXEMHFWQXPEHUZLOOEHNHSWLQWKH6LWH
0DVWHU)LOH
 
6XEMHFW:LWKGUDZDODQG5HSODFHPHQW
$VXEMHFWLVIUHHWRZLWKGUDZIURPWKHVWXG\DWDQ\WLPH,QDGGLWLRQDVXEMHFWZLOOEH
ZLWKGUDZQIURPGRVLQJLIDQ\RIWKHIROORZLQJFULWHULDDUHPHW
x FKDQJHLQFRPSOLDQFHZLWKDQ\LQFOXVLRQH[FOXVLRQFULWHULRQWKDWLVFOLQLFDOO\UHOHYDQW
DQGDIIHFWVVXEMHFWVDIHW\DVGHWHUPLQHGE\WKHLQYHVWLJDWRU
x QRQFRPSOLDQFHZLWKWKHVWXG\UHVWULFWLRQVWKDWPLJKWDIIHFWVXEMHFWVDIHW\RUVWXG\
DVVHVVPHQWVREMHFWLYHVDVFRQVLGHUHGDSSOLFDEOHE\WKHLQYHVWLJDWRU
x DQ\FOLQLFDOO\UHOHYDQWVLJQRUV\PSWRPWKDWLQWKHRSLQLRQRIWKHLQYHVWLJDWRU
ZDUUDQWVVXEMHFWZLWKGUDZDO
,IDVXEMHFWLVZLWKGUDZQIURPGRVLQJWKHVSRQVRUZLOOEHQRWLILHGDQGWKHGDWHDQGUHDVRQV
IRUWKHZLWKGUDZDOZLOOEHGRFXPHQWHGLQWKHVXEMHFW¶VHOHFWURQLFFDVHUHSRUWIRUPH&5)
,IDVXEMHFWLVZLWKGUDZQHIIRUWVZLOOEHPDGHWRSHUIRUPDOOIROORZXSDVVHVVPHQWVLI
SRVVLEOH$SSHQGL[2WKHUSURFHGXUHVPD\EHSHUIRUPHGDWWKHLQYHVWLJDWRU¶VDQGRU
VSRQVRU¶VGLVFUHWLRQ,IWKHVXEMHFWLVLQKRXVHWKHVHSURFHGXUHVVKRXOGEHSHUIRUPHGEHIRUH
WKHVXEMHFWLVGLVFKDUJHGIURPWKHFOLQLF7KHLQYHVWLJDWRUPD\DOVRUHTXHVWWKDWWKHVXEMHFW


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
UHWXUQIRUDQDGGLWLRQDOIROORZXSYLVLW$OOZLWKGUDZQVXEMHFWVZLOOEHIROORZHGXQWLO
UHVROXWLRQRIDOOWKHLU$(VRUXQWLOWKHFRQGLWLRQVWDELOL]HVRULVFRQVLGHUHGFKURQLFRUQRW
FOLQLFDOO\VLJQLILFDQWSHUWKHLQYHVWLJDWRUWKH$(RU6$(LVRWKHUZLVHH[SODLQHGWKHVXEMHFWLV
ORVWWRIROORZXSRUWKHVXEMHFWZLWKGUDZVFRQVHQW
6XEMHFWVZKRDUHZLWKGUDZQIRUUHDVRQVQRWUHODWHGWRVWXG\WUHDWPHQWPD\EHUHSODFHG
IROORZLQJGLVFXVVLRQEHWZHHQWKHLQYHVWLJDWRUDQGWKHVSRQVRU6XEMHFWVZLWKGUDZQDVDUHVXOW
RI$(VWKRXJKWWREHUHODWHGWRWKHVWXG\WUHDWPHQWZLOOJHQHUDOO\QRWEHUHSODFHG
 
6WXG\7HUPLQDWLRQ
7KHVWXG\PD\EHGLVFRQWLQXHGDWWKHGLVFUHWLRQRIWKHLQYHVWLJDWRUVSRQVRURUVSRQVRU¶V
PHGLFDOPRQLWRULIDQ\RIWKHIROORZLQJFULWHULDDUHPHW
x $(VXQNQRZQWRGDWHLHQRWSUHYLRXVO\UHSRUWHGLQDQ\VLPLODULQYHVWLJDWLRQDOVWXG\
GUXJWULDOZLWKUHVSHFWWRWKHLUQDWXUHVHYHULW\DQGRUGXUDWLRQ
x LQFUHDVHGIUHTXHQF\VHYHULW\DQGRUGXUDWLRQRINQRZQDQWLFLSDWHGRUSUHYLRXVO\
UHSRUWHG$(VWKLVPD\DOVRDSSO\WR$(VGHILQHGDWFKHFNLQDVEDVHOLQHVLJQVDQG
V\PSWRPV
x PHGLFDORUHWKLFDOUHDVRQVDIIHFWLQJWKHFRQWLQXHGSHUIRUPDQFHRIWKHVWXG\
x GLIILFXOWLHVLQWKHUHFUXLWPHQWRIVXEMHFWV
x FDQFHODWLRQRIGUXJGHYHORSPHQW
 678'<75($70(176
 
'HVFULSWLRQ6WRUDJH3DFNDJLQJDQG/DEHOLQJ
=DQXEUXWLQLEFDSVXOHVFRQWDLQLQJPJ]DQXEUXWLQLEZLOOEHVXSSOLHGE\WKHVSRQVRU
RUGHVLJQHHDORQJZLWKWKHEDWFKORWQXPEHU=DQXEUXWLQLEZLOOEHSURYLGHGLQKLJKGHQVLW\
SRO\HWK\OHQHERWWOHV=DQXEUXWLQLEERWWOHVPXVWEHVWRUHGDWURRPWHPSHUDWXUH&WR&
>)WR)@7KHVKHOIOLIHRI]DQXEUXWLQLELVHVWDEOLVKHGEDVHGRQRQJRLQJVWDELOLW\
VWXGLHVDQGPD\EHH[WHQGHGGXULQJWKHVWXG\7KHVLWHZLOOEHUHTXLUHGWRNHHSDWHPSHUDWXUH
ORJWRHVWDEOLVKDUHFRUGRIFRPSOLDQFHZLWKWKHVHVWRUDJHFRQGLWLRQV
7KHLQYHVWLJDWRURUGHVLJQHHRUVLWHZLOOFRPPHUFLDOO\VRXUFHULIDEXWLQFDSVXOHVFRQWDLQLQJ
PJ$OOVWXG\GUXJVZLOOEHVWRUHGDFFRUGLQJWRWKHPDQXIDFWXUHUV¶LQVWUXFWLRQV
6WXG\GUXJVZLOOEHVWRUHGDWWKHVWXG\VLWHLQDORFDWLRQWKDWLVORFNHGZLWKUHVWULFWHGDFFHVV
DQGNHSWXQGHUSK\VLFDOFRQGLWLRQVWKDWDUHFRQVLVWHQWZLWKVWXG\GUXJVSHFLILFUHTXLUHPHQWV
7KHEXONGUXJFRQWDLQHUDQGXQLWGRVHFRQWDLQHUVZLOOEHODEHOHGLQDFFRUGDQFHZLWKQDWLRQDO
ODZVDQGUHJXODWLRQV7KHODEHOZLOOLQFOXGHDWDPLQLPXPGUXJQDPHGRVHVWUHQJWK
FRQWHQWVVSRQVRUSURWRFROQXPEHUORWEDWFKQXPEHUGLUHFWLRQVIRUXVHVWRUDJHFRQGLWLRQV
FDXWLRQVWDWHPHQWVUHWHVWRUH[SLU\GDWHDQGVSDFHWRHQWHUWKHVXEMHFWQXPEHUDQGQDPHRI
WKHLQYHVWLJDWRU7KHVWXG\GUXJVZLOOEHWUDQVIHUUHGIURPEXONVXSSOLHVLQWRWKHVXEMHFW¶V
GRVHFRQWDLQHUE\TXDOLILHGFOLQLFDOVWDII


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 
6WXG\7UHDWPHQW$GPLQLVWUDWLRQ
$OOVXEMHFWVZLOOUHFHLYHHDFKRIWKHIROORZLQJWUHDWPHQWV
x VLQJOHGRVHRIPJ]DQXEUXWLQLEJLYHQRUDOO\DVîPJFDSVXOHVLQWKHIDVWHG
VWDWHRQ'D\VDQG
x PJULIDEXWLQ4'JLYHQRUDOO\DVîPJFDSVXOHVZLWKIRRGRQ'D\VWR
DQGLQWKHIDVWHGVWDWHRQ'D\
6HH6HFWLRQIRUIDVWLQJUHTXLUHPHQWVDQGZDWHUUHVWULFWLRQV
(DFKGRVHRI]DQXEUXWLQLEDQGULIDEXWLQZLOOEHDGPLQLVWHUHGRUDOO\ZLWKDSSUR[LPDWHO\
P/RIURRPWHPSHUDWXUHZDWHU:KHQ]DQXEUXWLQLEDQGULIDEXWLQDUHDGPLQLVWHUHG
FRQFXUUHQWO\DQDGGLWLRQDODPRXQWXSWRP/RIURRPWHPSHUDWXUHZDWHUPD\EH
DGPLQLVWHUHG
6XEMHFWVZLOOEHGRVHGLQQXPHULFDORUGHUZKLOHVHDWHGDQGZLOOQRWEHSHUPLWWHGWROLHVXSLQH
IRUKRXUVDIWHUVWXG\GUXJDGPLQLVWUDWLRQH[FHSWDVQHFHVVLWDWHGE\WKHRFFXUUHQFHRIDQ
$(VDQGRUVWXG\SURFHGXUHV
 
5DQGRPL]DWLRQ
7KLVLVDQRQUDQGRPL]HGVWXG\7KHVWXG\KDVDIL[HGWUHDWPHQWVHTXHQFH
 
%OLQGLQJ
7KLVLVDQRSHQODEHOVWXG\
 
7UHDWPHQW&RPSOLDQFH
7KHIROORZLQJPHDVXUHVZLOOEHHPSOR\HGWRHQVXUHWUHDWPHQWFRPSOLDQFH
x $OOGRVHVZLOOEHDGPLQLVWHUHGXQGHUWKHVXSHUYLVLRQRIVXLWDEO\TXDOLILHGVWXG\VLWH
VWDII
x ,PPHGLDWHO\DIWHUGRVHDGPLQLVWUDWLRQYLVXDOLQVSHFWLRQRIWKHPRXWKDQGKDQGVZLOO
EHSHUIRUPHGIRUHDFKVXEMHFW
x $WHDFKGRVHSUHSDUDWLRQRFFDVLRQDQLQYHQWRU\RI]DQXEUXWLQLEDQGULIDEXWLQZLOOEH
SHUIRUPHG
 
'UXJ$FFRXQWDELOLW\
7KHLQYHVWLJDWRURUGHVLJQHHZLOOPDLQWDLQDQDFFXUDWHUHFRUGRIWKHUHFHLSWRI]DQXEUXWLQLE
FDSVXOHVUHFHLYHG,QDGGLWLRQDQDFFXUDWHGUXJGLVSRVLWLRQUHFRUGZLOOEHNHSWVSHFLI\LQJWKH
DPRXQWGLVSHQVHGWRHDFKVXEMHFWWKHGDWHRIGLVSHQVLQJDQGTXDQWLWLHVGLVSRVHGRIRU
UHWXUQHGWRWKHVSRQVRU7KLVGUXJDFFRXQWDELOLW\UHFRUGZLOOEHDYDLODEOHIRULQVSHFWLRQDWDQ\
WLPH$WWKHFRPSOHWLRQRIWKHVWXG\WKHRULJLQDOGUXJDFFRXQWDELOLW\UHFRUGZLOOEHDYDLODEOH
IRUUHYLHZE\WKHVSRQVRUXSRQUHTXHVW


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
)RUHDFKEDWFKRIXQLWGRVHVWKHHPSW\XVHGXQLWGRVHFRQWDLQHUVZLOOEHGLVFDUGHGXSRQ
VDWLVIDFWRU\FRPSOHWLRQRIWKHFRPSOLDQFHDQGDFFRXQWDELOLW\SURFHGXUHV$Q\XQXVHG
DVVHPEOHGXQLWGRVHVZLOOEHUHWDLQHGXQWLOFRPSOHWLRQRIWKHVWXG\
$WWKHFRPSOHWLRQRIWKHVWXG\DOOXQXVHG]DQXEUXWLQLEFDSVXOHVZLOOEHUHWXUQHGWRWKH
VSRQVRURUGLVSRVHGRIE\WKHVWXG\VLWHSHUWKHVSRQVRU¶VZULWWHQLQVWUXFWLRQV
5LIDEXWLQZLOODOVREHVXEMHFWWRDFFRXQWDELOLW\SURFHGXUHVDQGWKH&58VWDIIZLOOGHVWUR\
XQXVHGVXSSOLHVDWWKHHQGRIWKHVWXG\
 &21&20,7$177+(5$3,(6$1'27+(55(675,&7,216
 
&RQFRPLWDQW7KHUDSLHV
6XEMHFWVZLOOUHIUDLQIURPXVHRIDQ\SUHVFULSWLRQRUQRQSUHVFULSWLRQPHGLFDWLRQVSURGXFWV
GXULQJWKHVWXG\XQWLOWKHIROORZXSYLVLWXQOHVVWKHLQYHVWLJDWRUDQGRUVSRQVRUKDYHJLYHQ
WKHLUSULRUFRQVHQW
$FHWDPLQRSKHQJGD\IRUXSWRFRQVHFXWLYHGD\VLVDQDFFHSWDEOHFRQFRPLWDQW
PHGLFDWLRQ7KHDGPLQLVWUDWLRQRIDQ\RWKHUFRQFRPLWDQWPHGLFDWLRQVGXULQJWKHVWXG\LV
SURKLELWHGZLWKRXWSULRUDSSURYDORIWKHLQYHVWLJDWRUXQOHVVLWVXVHLVGHHPHGQHFHVVDU\LQD
PHGLFDOHPHUJHQF\$Q\PHGLFDWLRQWDNHQE\DVXEMHFWGXULQJWKHFRXUVHRIWKHVWXG\DQGWKH
UHDVRQIRULWVXVHZLOOEHGRFXPHQWHGLQWKHVRXUFHGDWD
 
'LHW
:KLOHFRQILQHGDWWKHVWXG\VLWHVXEMHFWVZLOOUHFHLYHDVWDQGDUGL]HGGLHWDWVFKHGXOHGWLPHV
WKDWGRQRWFRQIOLFWZLWKRWKHUVWXG\UHODWHGDFWLYLWLHV6XEMHFWVZLOOEHIDVWHGRYHUQLJKWDW
OHDVWKRXUVEHIRUHFROOHFWLRQRIEORRGVDPSOHVIRUFOLQLFDOODERUDWRU\HYDOXDWLRQV
2Q3.VDPSOLQJGD\V'D\VDQG]DQXEUXWLQLEDQGULIDEXWLQZLOOEHDGPLQLVWHUHG
IROORZLQJDQRYHUQLJKWIDVWRIWRKRXUV6XEMHFWVZLOOUHIUDLQIURPFRQVXPLQJ
ZDWHUIOXLGVIURPKRXUSUHGRVHXQWLOKRXUSRVWGRVHH[FOXGLQJWKHDPRXQWRIZDWHU
FRQVXPHGDWGRVLQJ)RRGLVDOORZHGIURPKRXUVSRVWGRVH$WDOORWKHUWLPHVGXULQJWKH
VWXG\VXEMHFWVPD\FRQVXPHZDWHURQDQDGOLELWXPEDVLV
)RRGVDQGEHYHUDJHVFRQWDLQLQJSRSS\VHHGVJUDSHIUXLWRU6HYLOOHRUDQJHVZLOOQRWEH
DOORZHGIURPGD\VSULRUWRFKHFNLQXQWLOGLVFKDUJHRQ'D\
&DIIHLQHFRQWDLQLQJIRRGVDQGEHYHUDJHVZLOOQRWEHDOORZHGIURPKRXUVEHIRUHFKHFNLQ
XQWLOGLVFKDUJHRQ'D\
&RQVXPSWLRQRIDOFRKROZLOOQRWEHSHUPLWWHGIURPKRXUVSULRUWRFKHFNLQXQWLOGLVFKDUJH
RQ'D\
 
6PRNLQJ
6XEMHFWVZLOOQRWEHSHUPLWWHGWRXVHWREDFFRRUQLFRWLQHFRQWDLQLQJSURGXFWVZLWKLQ
PRQWKVSULRUWRFKHFNLQXQWLOGLVFKDUJHRQ'D\


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 
([HUFLVH
6XEMHFWVDUHUHTXLUHGWRUHIUDLQIURPVWUHQXRXVH[HUFLVHIURPGD\VEHIRUHFKHFNLQXQWLOWKH
IROORZXSYLVLWDQGZLOORWKHUZLVHPDLQWDLQWKHLUQRUPDOOHYHORISK\VLFDODFWLYLW\GXULQJWKLV
WLPHLHZLOOQRWEHJLQDQHZH[HUFLVHSURJUDPQRUSDUWLFLSDWHLQDQ\XQXVXDOO\VWUHQXRXV
SK\VLFDOH[HUWLRQ
 
%ORRG'RQDWLRQ
6XEMHFWVDUHUHTXLUHGWRUHIUDLQIURPGRQDWLRQRIEORRGIURPZHHNVSULRUWRVFUHHQLQJ
SODVPDIURPZHHNVSULRUWRVFUHHQLQJDQGSODWHOHWVIURPZHHNVSULRUWRVFUHHQLQJXQWLO
ZHHNVDIWHUWKHIROORZXSYLVLW
 
&RQWUDFHSWLRQ
6XEMHFWVDUHUHTXLUHGWRUHIUDLQIURPGRQDWLRQRIVSHUPIURPWKHWLPHRIWKHILUVWGRVHRI
]DQXEUXWLQLEXQWLOGD\VDIWHUWKHODVWGRVHRI]DQXEUXWLQLE
6XEMHFWVHQUROOHGLQWKHVWXG\PXVWXVHEDUULHUFRQWUDFHSWLRQZLWKRWKHUKLJKO\HIIHFWLYH
PHWKRGVRIFRQWUDFHSWLRQLIKHKDVDIHPDOHSDUWQHURIFKLOGEHDULQJSRWHQWLDOZKRLVQRW
SHUPDQHQWO\VWHULOHYLDK\VWHUHFWRP\ELODWHUDOVDOSLQJHFWRP\DQGELODWHUDORRSKRUHFWRP\
RUQRWSRVWPHQRSDXVDO
$ZRPDQLVFRQVLGHUHGRIFKLOGEHDULQJSRWHQWLDOLHIHUWLOHIROORZLQJPHQDUFKHDQGXQWLO
EHFRPLQJSRVWPHQRSDXVDO&RQWUDFHSWLRQPHWKRGVLQFOXGHWKHIROORZLQJ
x &RPELQHGHVWURJHQDQGSURJHVWRJHQFRQWDLQLQJKRUPRQDOFRQWUDFHSWLRQDVVRFLDWHG
ZLWKWKHLQKLELWLRQRIRYXODWLRQ
 2UDOLQWUDYDJLQDORUWUDQVGHUPDO
x 3URJHVWRJHQRQO\KRUPRQDOFRQWUDFHSWLRQDVVRFLDWHGZLWKWKHLQKLELWLRQRIRYXODWLRQ
 2UDOLQMHFWDEOHLPSODQWDEOH
x $QLQWUDXWHULQHGHYLFH
x ,QWUDXWHULQHKRUPRQHUHOHDVLQJV\VWHP
x %LODWHUDOWXEDORFFOXVLRQ
x 9DVHFWRPL]HGSDUWQHUSURYLGHGWKDWWKHYDVHFWRPL]HGSDUWQHULVWKHVROHVH[XDO
SDUWQHURIWKHZRPDQRIFKLOGEHDULQJSRWHQWLDOVWXG\SDUWLFLSDQWDQGWKDWWKH
YDVHFWRPL]HGSDUWQHUKDVUHFHLYHGPHGLFDODVVHVVPHQWRIVXUJLFDOVXFFHVV
x 6H[XDODEVWLQHQFHGHILQHGDVUHIUDLQLQJIURPKHWHURVH[XDOLQWHUFRXUVHGXULQJWKH
HQWLUHSHULRGRIULVNDVVRFLDWHGZLWKWKHVWXG\WUHDWPHQWVWDUWLQJWKHGD\SULRUWRILUVW
GRVHRIVWXG\GUXJIRUWKHGXUDWLRQRIWKHVWXG\DQGIRUGD\VDIWHUWKHODVWGRVH
RI]DQXEUXWLQLE7RWDOVH[XDODEVWLQHQFHVKRXOGRQO\EHXVHGDVDFRQWUDFHSWLYH
PHWKRGLILWLVLQOLQHZLWKWKHVXEMHFW¶VXVXDODQGSUHIHUUHGOLIHVW\OH3HULRGLF
DEVWLQHQFHHJFDOHQGDURYXODWLRQV\PSWRWKHUPDOSRVWRYXODWLRQPHWKRGV
GHFODUDWLRQRIDEVWLQHQFHIRUWKHGXUDWLRQRIH[SRVXUHWRLQYHVWLJDWLRQDOPHGLFLQDO
SURGXFWDQGZLWKGUDZDODUHQRWDFFHSWDEOHPHWKRGVRIFRQWUDFHSWLRQ


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
2IQRWHEDUULHUFRQWUDFHSWLRQLQFOXGLQJPDOHDQGIHPDOHFRQGRPVZLWKRUZLWKRXW
VSHUPLFLGHLVQRWFRQVLGHUHGDKLJKO\HIIHFWLYHPHWKRGRIFRQWUDFHSWLRQDQGLIXVHGWKLV
PHWKRGPXVWEHXVHGLQFRPELQDWLRQZLWKDQRWKHUDFFHSWDEOHPHWKRGOLVWHGDERYH
,IWKHVXEMHFW¶VIHPDOHSDUWQHULVXVLQJKRUPRQDOFRQWUDFHSWLYHVVXFKDVELUWKFRQWUROSLOOVRU
GHYLFHVDEDUULHUPHWKRGRIFRQWUDFHSWLRQHJFRQGRPVPXVWDOVREHXVHG
$SRVWPHQRSDXVDOVWDWHLVGHILQHGDVQRPHQVHVIRUPRQWKVZLWKRXWDQDOWHUQDWLYHPHGLFDO
FDXVH
 678'<$66(660(176$1'352&('85(6
(YHU\HIIRUWZLOOEHPDGHWRVFKHGXOHDQGSHUIRUPWKHSURFHGXUHVDVFORVHO\DVSRVVLEOHWRWKH
QRPLQDOWLPHJLYLQJFRQVLGHUDWLRQVWRDSSURSULDWHSRVWXUHFRQGLWLRQVSUDFWLFDOUHVWULFWLRQV
DQGWKHRWKHUSURFHGXUHVWREHSHUIRUPHGDWWKHVDPHWLPHSRLQW
7KHKLJKHVWSULRULW\SURFHGXUHVZLOOEHSHUIRUPHGFORVHVWWRWKHQRPLQDOWLPH7KHRUGHURI
SULRULW\IRUVFKHGXOLQJSURFHGXUHVDURXQGDWLPHSRLQWLVLQGHVFHQGLQJRUGHURISULRULW\
x GRVLQJ
x EORRGVDPSOHVIRU]DQXEUXWLQLEDVVD\
x DQ\RWKHUSURFHGXUHV(&*VZLOOEHVFKHGXOHGEHIRUHYLWDOVLJQPHDVXUHPHQWV
 
3KDUPDFRNLQHWLF$VVHVVPHQWV
 
3KDUPDFRNLQHWLF%ORRG6DPSOH&ROOHFWLRQDQG3URFHVVLQJ
%ORRGVDPSOHVZLOOEHFROOHFWHGE\YHQLSXQFWXUHDWWKHWLPHVLQGLFDWHGLQWKH6FKHGXOHRI
$VVHVVPHQWVLQ$SSHQGL[3URFHGXUHVIRUFROOHFWLRQSURFHVVLQJDQGVKLSSLQJRI3.
VDPSOHVZLOOEHGHWDLOHGLQDVHSDUDWHGRFXPHQW
7KHLQGLYLGXDOEORRGYROXPHUHTXLUHPHQWIRU]DQXEUXWLQLELVOLVWHGLQ$SSHQGL[7KHWRWDO
EORRGYROXPHUHTXLUHGIRUDOODQDO\VHVLVSUHVHQWHGLQ$SSHQGL[
/HIWRYHUSODVPDVDPSOHVPD\EHXVHGWRFKDUDFWHUL]HDQ\SRWHQWLDOPHWDEROLWHVRI
]DQXEUXWLQLE
 
$QDO\WLFDO0HWKRGRORJ\
3ODVPDFRQFHQWUDWLRQVRI]DQXEUXWLQLEZLOOEHGHWHUPLQHGXVLQJDYDOLGDWHGDQDO\WLFDO
SURFHGXUH6SHFLILFVRIWKHDQDO\WLFDOPHWKRGZLOOEHSURYLGHGLQDVHSDUDWHGRFXPHQW
 
6DIHW\DQG7ROHUDELOLW\$VVHVVPHQWV
 
$GYHUVH(YHQWV
$GYHUVHHYHQWGHILQLWLRQVDVVLJQPHQWRIVHYHULW\DQGFDXVDOLW\DQGSURFHGXUHVIRUUHSRUWLQJ
VHULRXV$(V6$(VDUHGHWDLOHGLQ$SSHQGL[


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
7KHFRQGLWLRQRIHDFKVXEMHFWZLOOEHPRQLWRUHGIURPWKHWLPHRIVLJQLQJWKH,&)WRVWXG\
FRPSOHWLRQ6XEMHFWVZLOOEHREVHUYHGIRUDQ\VLJQVRUV\PSWRPVDQGDVNHGDERXWWKHLU
FRQGLWLRQE\RSHQTXHVWLRQLQJVXFKDV³+RZKDYH\RXEHHQIHHOLQJVLQFH\RXZHUHODVW
DVNHG"´DWOHDVWRQFHHDFKGD\ZKLOHUHVLGHQWDWWKH&58DQGDWWKHIROORZXSYLVLW6XEMHFWV
ZLOODOVREHHQFRXUDJHGWRVSRQWDQHRXVO\UHSRUW$(VRFFXUULQJDWDQ\RWKHUWLPHGXULQJWKH
VWXG\
$OOQRQVHULRXV$(VZKHWKHUUHSRUWHGE\WKHVXEMHFWYROXQWDULO\RUXSRQTXHVWLRQLQJRU
QRWHGRQSK\VLFDOH[DPLQDWLRQZLOOEHUHFRUGHGIURPWKHWLPHRIVWXG\GUXJDGPLQLVWUDWLRQ
XQWLOVWXG\FRPSOHWLRQ$OO6$(VZLOOEHUHFRUGHGIURPWKHWLPHWKHVXEMHFWVLJQVWKH,&)
XQWLOVWXG\FRPSOHWLRQ7KHQDWXUHWLPHRIRQVHWGXUDWLRQDQGVHYHULW\ZLOOEHGRFXPHQWHG
WRJHWKHUZLWKDQLQYHVWLJDWRU¶VRSLQLRQRIWKHUHODWLRQVKLSWRVWXG\WUHDWPHQW
$OO$(VDQG6$(VUHFRUGHGGXULQJWKHFRXUVHRIWKHVWXG\ZLOOEHIROORZHGXQWLOUHVROXWLRQ
WKHFRQGLWLRQVWDELOL]HVRULVFRQVLGHUHGFKURQLFRUQRWFOLQLFDOO\VLJQLILFDQWSHUWKH
LQYHVWLJDWRUWKH$(RU6$(LVRWKHUZLVHH[SODLQHGWKHVXEMHFWLVORVWWRIROORZXSRUWKH
VXEMHFWZLWKGUDZVFRQVHQW7KLVZLOOEHFRPSOHWHGDWWKHLQYHVWLJDWRU¶VRUGHVLJQHH¶V
GLVFUHWLRQ
 
&OLQLFDO/DERUDWRU\(YDOXDWLRQV
%ORRGDQGXULQHVDPSOHVZLOOEHFROOHFWHGIRUFOLQLFDOODERUDWRU\HYDOXDWLRQVDWWKHWLPHV
LQGLFDWHGLQWKH6FKHGXOHRI$VVHVVPHQWVLQ$SSHQGL[&OLQLFDOODERUDWRU\HYDOXDWLRQVDUH
OLVWHGLQ$SSHQGL[
6XEMHFWVZLOOEHDVNHGWRSURYLGHXULQHVDPSOHVIRUGUXJVRIDEXVHVFUHHQDQGFRWLQLQHWHVW
DQGZLOOXQGHUJRDQDOFRKROWHVWDWWKHWLPHVLQGLFDWHGLQWKH6FKHGXOHRI$VVHVVPHQWVLQ
$SSHQGL[
$QLQYHVWLJDWRURUGHVLJQHHZLOOSHUIRUPDFOLQLFDODVVHVVPHQWRIDOOFOLQLFDOODERUDWRU\GDWD
$OOFOLQLFDOO\VLJQLILFDQWFOLQLFDOODERUDWRU\UHVXOWVZLOOEHUHSRUWHGDV$(VE\WKH
LQYHVWLJDWRU
 
9LWDO6LJQV
6XSLQHEORRGSUHVVXUHVXSLQHSXOVHUDWHUHVSLUDWRU\UDWHDQGRUDOERG\WHPSHUDWXUHZLOOEH
DVVHVVHGDWWKHWLPHVLQGLFDWHGLQWKH6FKHGXOHRI$VVHVVPHQWVLQ$SSHQGL[9LWDOVLJQV
PD\DOVREHSHUIRUPHGDWRWKHUWLPHVLIMXGJHGWREHFOLQLFDOO\DSSURSULDWHRULIWKHRQJRLQJ
UHYLHZRIWKHGDWDVXJJHVWVDPRUHGHWDLOHGDVVHVVPHQWRIYLWDOVLJQVLVUHTXLUHG
$OOPHDVXUHPHQWVZLOOEHSHUIRUPHGVLQJO\DQGUHSHDWHGRQFHLIRXWVLGHWKHUHOHYDQWFOLQLFDO
UHIHUHQFHUDQJH
6XEMHFWVPXVWEHVXSLQHIRUDWOHDVWPLQXWHVEHIRUHEORRGSUHVVXUHDQGSXOVHUDWH
PHDVXUHPHQWV
$OOFOLQLFDOO\VLJQLILFDQWYLWDOVLJQPHDVXUHPHQWVZLOOEHUHSRUWHGDV$(VE\WKHLQYHVWLJDWRU


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 
/HDG(OHFWURFDUGLRJUDP
5HVWLQJOHDG(&*VZLOOEHUHFRUGHGDIWHUWKHVXEMHFWKDVEHHQVXSLQHDQGDWUHVWIRUDW
OHDVWPLQXWHVDWWKHWLPHVLQGLFDWHGLQWKH6FKHGXOHRI$VVHVVPHQWVLQ$SSHQGL[6LQJOH
OHDG(&*VZLOOEHUHSHDWHGWZLFHDQGDQDYHUDJHWDNHQRIWKHUHDGLQJVLIHLWKHURIWKH
IROORZLQJFULWHULDDSSO\
x 47F)!PVHF
x 47F)FKDQJHIURPWKHEDVHOLQHSUHGRVH!PVHF
$GGLWLRQDOOHDG(&*VPD\EHSHUIRUPHGDWRWKHUWLPHVLIMXGJHGWREHFOLQLFDOO\
DSSURSULDWHRULIWKHRQJRLQJUHYLHZRIWKHGDWDVXJJHVWVDPRUHGHWDLOHGDVVHVVPHQWRI(&*V
LVUHTXLUHG7KHLQYHVWLJDWRURUGHVLJQHHZLOOSHUIRUPDFOLQLFDODVVHVVPHQWRIHDFKOHDG
(&*
$OOFOLQLFDOO\VLJQLILFDQW(&*UHVXOWVZLOOEHUHSRUWHGDV$(VE\WKHLQYHVWLJDWRU
 
3K\VLFDO([DPLQDWLRQ
$IXOOSK\VLFDOH[DPLQDWLRQRUV\PSWRPGLUHFWHGSK\VLFDOH[DPLQDWLRQZLOOEHSHUIRUPHGDW
WKHWLPHSRLQWVVSHFLILHGLQWKH6FKHGXOHRI$VVHVVPHQWVLQ$SSHQGL[
7KHIXOOSK\VLFDOH[DPLQDWLRQZLOOLQFOXGHDVVHVVPHQWRIVNLQKHDGHDUVH\HVQRVHWKURDW
QHFNWK\URLGOXQJVKHDUWFDUGLRYDVFXODUV\VWHPDEGRPHQO\PSKQRGHVDQG
PXVFXORVNHOHWDOV\VWHPH[WUHPLWLHV,QWHULPSK\VLFDOH[DPLQDWLRQVZLOOEHSHUIRUPHGDV
QHFHVVDU\DWWKHGLVFUHWLRQRIWKHLQYHVWLJDWRUWRHYDOXDWH$(VRUFOLQLFDOODERUDWRU\
DEQRUPDOLWLHV
$OOFOLQLFDOO\VLJQLILFDQWSK\VLFDOH[DPLQDWLRQUHVXOWVZLOOEHUHSRUWHGDV$(VE\WKH
LQYHVWLJDWRU
 6$03/(6,=($1''$7$$1$/<6,6
 
'HWHUPLQDWLRQRI6DPSOH6L]H
$SSUR[LPDWHO\VXEMHFWVZLOOEHHQUROOHGWRHQVXUHWKDWVXEMHFWVFRPSOHWHWKHVWXG\
7KHVDPSOHVL]HFKRVHQIRUWKLVVWXG\ZDVEDVHGRQSUHFHGHQWVHWE\RWKHU3.VWXGLHVRI
VLPLODUQDWXUHDQGZDVQRWEDVHGRQSRZHUFDOFXODWLRQV
 
$QDO\VLV3RSXODWLRQV
 
3KDUPDFRNLQHWLF3RSXODWLRQ
7KH3.SRSXODWLRQZLOOLQFOXGHDOOVXEMHFWVZKRUHFHLYHGDWOHDVWGRVHRI]DQXEUXWLQLEDQG
KDYHHYDOXDEOH3.GDWDDWOHDVW3.SDUDPHWHUFDQEHFDOFXODWHG$VXEMHFWZLOOEH
H[FOXGHGIURPWKH3.VXPPDU\VWDWLVWLFVDQGVWDWLVWLFDODQDO\VLVLIWKHVXEMHFWKDVDQ$(RI
YRPLWLQJWKDWRFFXUVDWRUEHIRUHîPHGLDQ7PD[


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 
6DIHW\3RSXODWLRQ
7KHVDIHW\SRSXODWLRQZLOOLQFOXGHDOOVXEMHFWVZKRUHFHLYHGDWOHDVWGRVHRI]DQXEUXWLQLE
 
3KDUPDFRNLQHWLF$QDO\VHV
7KHSODVPD3.SDUDPHWHUVRI]DQXEUXWLQLEIROORZLQJ]DQXEUXWLQLEGRVLQJRQ'D\VDQG
ZLOOEHFDOFXODWHGIURP]DQXEUXWLQLEFRQFHQWUDWLRQWLPHSURILOHVXVLQJVWDQGDUG
QRQFRPSDUWPHQWDOPHWKRGV/HIWRYHUSODVPDVDPSOHVPD\EHDQDO\]HGIRUPHWDEROLWHVRI
LQWHUHVW
7KHSULPDU\3.SDUDPHWHUVDUH$8&W$8&&PD[7PD[W&/)DQG9])IRU
]DQXEUXWLQLE2WKHU3.SDUDPHWHUVPD\EHUHSRUWHGEXWZLOOEHUHJDUGHGDVVHFRQGDU\DQG
ZLOOQRWEHVXEMHFWWRLQIHUHQWLDOVWDWLVWLFDODQDO\VLV
$OLQHDUPL[HGPRGHODQDO\VLVZLOOEHDSSOLHGWRDQDO\]HWKHORJWUDQVIRUPHGSULPDU\3.
SDUDPHWHUV$8&W$8&DQG&PD[7KHPRGHODVVXPHVDIL[HGHIIHFWIRUWUHDWPHQWDQGD
UDQGRPHIIHFWIRUVXEMHFW
(VWLPDWHVRIJHRPHWULFPHDQUDWLRVWRJHWKHUZLWKWKHFRUUHVSRQGLQJFRQILGHQFHLQWHUYDOV
ZLOOEHGHULYHGIRUWKHFRPSDULVRQVRIWKH3.SDUDPHWHUVDVIROORZV
x ]DQXEUXWLQLESOXVULIDEXWLQWHVW'D\YHUVXV]DQXEUXWLQLEDORQHUHIHUHQFH'D\
 
6DIHW\$QDO\VLV
$YHUEDWLPGHVFULSWLRQRI$(VZLOOEHPDSSHGWRWKH0HGLFDO'LFWLRQDU\IRU5HJXODWRU\
$FWLYLWLHV0HG'5$WHUPV$OOWUHDWPHQWHPHUJHQW$(VZLOOEHVXPPDUL]HG$
WUHDWPHQWHPHUJHQW$(LVGHILQHGDVDQ$(WKDWKDGDQRQVHWGDWHRQRUDIWHUWKHILUVWGRVHRI
VWXG\GUXJXSWRGD\VDIWHUWKHODVWWUHDWPHQWZLWK]DQXEUXWLQLERUZDVZRUVHQLQJLQ
VHYHULW\IURPEDVHOLQHSUHWUHDWPHQW

&OLQLFDOODERUDWRU\GDWDZLWKYDOXHVRXWVLGHRIWKHQRUPDOUDQJHVZLOOEHLGHQWLILHG2EVHUYHG
YDOXHVDQGFKDQJHVIURPEDVHOLQHODERUDWRU\GDWDYLWDOVLJQVDQG(&*UHVXOWVZLOOEH
VXPPDUL]HGE\YLVLW
 
,QWHULP$QDO\VLV
1RLQWHULPDQDO\VHVDUHSODQQHGIRUWKLVVWXG\


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 5()(5(1&(6
 %HL*HQH/WG%HL*HQH=DQXEUXWLQLE%*%±,QYHVWLJDWRU¶V%URFKXUH(GLWLRQ
1XPEHU-DQXDU\
 +XPSKULHV/$'DQJHOPDLHU&6RPPHU.HWDO7HFNLQDVHVPHGLDWHVXVWDLQHGFDOFLXP
LQIOX[YLDVLWHVSHFLILFW\URVLQHSKRVSKRU\ODWLRQRIWKHSKRVSKROLSDVH&JDPPD6UF
KRPRORJ\6UFKRPRORJ\OLQNHUJ Biol Chem
GRLMEF0
 $GYDQL5+%XJJ\--6KDUPDQ-3HWDO%UXWRQW\URVLQHNLQDVHLQKLELWRULEUXWLQLE
3&,KDVVLJQLILFDQWDFWLYLW\LQSDWLHQWVZLWKUHODSVHGUHIUDFWRU\%FHOO
PDOLJQDQFLHVJ Clin OncolGRL-&2
 3HWUR-%.KDQ:13KRVSKROLSDVH&JDPPDFRXSOHV%UXWRQ¶VW\URVLQHNLQDVHWRWKH
1)NDSSD%VLJQDOLQJSDWKZD\LQ%O\PSKRF\WHVJ Biol Chem
GRLMEF0
 1DKLG3'RUPDQ6($OLSDQDK1HWDO2IILFLDO$PHULFDQ7KRUDFLF6RFLHW\&HQWHUVIRU
'LVHDVH&RQWURODQG3UHYHQWLRQ,QIHFWLRXV'LVHDVHV6RFLHW\RI$PHULFD&OLQLFDO3UDFWLFH
*XLGHOLQHV7UHDWPHQWRI'UXJ6XVFHSWLEOH7XEHUFXORVLVClin Infect Dis2FW
HHGRLFLGFLZ
 /XW]-'.LUE\%-:DQJ/HWDO&\WRFKURPH3$,QGXFWLRQ3UHGLFWV
3JO\FRSURWHLQ,QGXFWLRQ3DUW3UHGLFWLRQRI'HFUHDVHG6XEVWUDWH([SRVXUH$IWHU
5LIDEXWLQRU&DUEDPD]HSLQHClin Pharmacol Ther
GRLFSW
 9RXUYDKLV0'DYLV-:DQJ5HWDO(IIHFWRIULIDPSLQDQGULIDEXWLQRQWKH
SKDUPDFRNLQHWLFVRIOHUVLYLULQHDQGHIIHFWRIOHUVLYLULQHRQWKHSKDUPDFRNLQHWLFVRI
ULIDEXWLQDQG2GHVDFHW\OULIDEXWLQLQKHDOWK\VXEMHFWVAntimicrob Agents Chemother
GRL$$&
 *KDQQDG0'HQQHK\0OD3RUWH&HWDO$GUXJLQWHUDFWLRQVWXG\LQYHVWLJDWLQJWKH
HIIHFWRI5LIDEXWLQRQWKHSKDUPDFRNLQHWLFVRI0DUDYLURFLQKHDOWK\VXEMHFWVPLoS One
HGRLMRXUQDOSRQH
 5LIDEXWLQ0\FREXWLQFDSVXOHV>SDFNDJHLQVHUW@1HZ<RUN1<3IL]HU5HYLVHG
2FWREHU
 )RRGDQG'UXJ$GPLQLVWUDWLRQ'UDIW*XLGDQFHIRU,QGXVWU\'UXJ,QWHUDFWLRQ
6WXGLHV6WXG\'HVLJQ'DWD$QDO\VLV,PSOLFDWLRQVIRU'RVLQJDQG/DEHOLQJ
5HFRPPHQGDWLRQV>,QWHUQHW@$YDLODEOHIURP
KWWSVZZZIGDJRYGRZQORDGVGUXJVJXLGDQFHVXFPSGI$FFHVVHG0DUFK





3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 $33(1',&(6


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
$SSHQGL[$GYHUVH(YHQW5HSRUWLQJ
7KHLQYHVWLJDWRULVUHVSRQVLEOHIRUWKHPRQLWRULQJDQGGRFXPHQWDWLRQRIHYHQWVWKDWPHHWWKH
FULWHULDDQGGHILQLWLRQVRIDQ$(RU6$(DVSURYLGHGLQWKLVSURWRFRO
 $GYHUVH(YHQWV
 
'HILQLWLRQDQG5HSRUWLQJRIDQ$GYHUVH(YHQW
$Q$(LVGHILQHGDV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
VWXG\GUXJZKHWKHUFRQVLGHUHGUHODWHGWRVWXG\GUXJRUQRW
([DPSOHVRIDQ$(LQFOXGH
x :RUVHQLQJRIDFKURQLFRULQWHUPLWWHQWSUHH[LVWLQJFRQGLWLRQLQFOXGLQJDQLQFUHDVHLQ
VHYHULW\IUHTXHQF\GXUDWLRQDQGRUKDVDQDVVRFLDWLRQZLWKDVLJQLILFDQWO\ZRUVH
RXWFRPH
x 1HZFRQGLWLRQVGHWHFWHGRUGLDJQRVHGDIWHUVWXG\GUXJDGPLQLVWUDWLRQHYHQWKRXJKLW
PD\KDYHEHHQSUHVHQWEHIRUHWKHVWDUWRIWKHVWXG\
x 6LJQVV\PSWRPVRUWKHFOLQLFDOVHTXHODHRIDVXVSHFWHGLQWHUDFWLRQ
x 6LJQVV\PSWRPVRUWKHFOLQLFDOVHTXHODHRIDVXVSHFWHGRYHUGRVHRIHLWKHUVWXG\GUXJ
RUDFRQFXUUHQWPHGLFDWLRQRYHUGRVHSHUVHVKRXOGQRWEHUHSRUWHGDVDQ$(RU6$(
:KHQDQ$(RU6$(RFFXUVLWLVWKHUHVSRQVLELOLW\RIWKHLQYHVWLJDWRUWRUHYLHZDOO
GRFXPHQWDWLRQHJKRVSLWDOSURJUHVVQRWHVODERUDWRU\UHVXOWVDQGGLDJQRVWLFVUHSRUWV
UHODWLYHWRWKH$(RU6$(7KHLQYHVWLJDWRUZLOOWKHQUHFRUGDOOUHOHYDQWLQIRUPDWLRQ
UHJDUGLQJDQ$(RU6$(LQWKHH&5)+RZHYHUWKHUHPD\EHLQVWDQFHVZKHQFRSLHVRI
PHGLFDOUHFRUGVIRUFHUWDLQFDVHVDUHUHTXHVWHGE\WKHVSRQVRU,QWKLVLQVWDQFHDOOVXEMHFW
LGHQWLILHUVZLOOEHEOLQGHGRQWKHFRSLHVRIWKHPHGLFDOUHFRUGVSULRUWRVXEPLVVLRQWRWKH
VSRQVRU
 
$VVHVVPHQWRI6HYHULW\
7KHLQYHVWLJDWRUZLOOPDNHDQDVVHVVPHQWRIVHYHULW\IRUHDFK$(DQG6$(UHSRUWHGGXULQJ
WKHVWXG\$GYHUVHHYHQWVDQG6$(VVKRXOGEHDVVHVVHGDQGJUDGHGEDVHGXSRQWKH1DWLRQDO
&DQFHU,QVWLWXWH1&,&RPPRQ7HUPLQRORJ\&ULWHULDIRU$GYHUVH(YHQWV&7&$(Y
7R[LFLWLHVWKDWDUHQRWVSHFLILHGLQWKH1&,&7&$(ZLOOEHGHILQHGDVIROORZV
x *UDGH0LOGDV\PSWRPDWLFRUPLOGV\PSWRPVFOLQLFDORUGLDJQRVWLFREVHUYDWLRQV
RQO\LQWHUYHQWLRQQRWLQGLFDWHG
x *UDGH0RGHUDWHPLQLPDOORFDORUQRQLQYDVLYHLQWHUYHQWLRQLQGLFDWHGOLPLWLQJ
DJHDSSURSULDWHLQVWUXPHQWDODFWLYLWLHVRIGDLO\OLYLQJ$'/
x *UDGH6HYHUHRUPHGLFDOO\VLJQLILFDQWEXWQRWLPPHGLDWHO\OLIHWKUHDWHQLQJ
KRVSLWDOL]DWLRQRUSURORQJDWLRQRIKRVSLWDOL]DWLRQLQGLFDWHGGLVDEOLQJOLPLWLQJ
VHOIFDUH$'/


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
x *UDGH/LIHWKUHDWHQLQJFRQVHTXHQFHVXUJHQWLQWHUYHQWLRQLQGLFDWHG
x *UDGH'HDWKUHODWHGWR$(
127(7KHWHUPV³VHYHUH´DQG³VHULRXV´DUHQRWV\QRQ\PRXV6HYHULW\LVDPHDVXUHRI
LQWHQVLW\HJJUDGHRIDVSHFLILF$(PLOG>*UDGH@PRGHUDWH>*UDGH@VHYHUH>*UDGH@
RUOLIHWKUHDWHQLQJ>*UDGH@ZKHUHDVVHULRXVQHVVLVFODVVLILHGE\WKHFULWHULDEDVHGRQWKH
UHJXODWRU\GHILQLWLRQV6HULRXVQHVVVHUYHVDVWKHJXLGHIRUGHILQLQJUHJXODWRU\UHSRUWLQJ
REOLJDWLRQVIURPWKHVSRQVRUWRDSSOLFDEOHUHJXODWRU\DXWKRULWLHVDVGHVFULEHGLQ
6HFWLRQ
 
$VVHVVPHQWRI&DXVDOLW\
7KHLQYHVWLJDWRULVREOLJDWHGWRDVVHVVWKHUHODWLRQVKLSEHWZHHQWKHVWXG\GUXJDQGWKH
RFFXUUHQFHRIHDFK$(RU6$(7KHLQYHVWLJDWRUZLOOXVHFOLQLFDOMXGJPHQWWRGHWHUPLQHWKH
UHODWLRQVKLS$OWHUQDWLYHFDXVHVVXFKDVQDWXUDOKLVWRU\RIWKHXQGHUO\LQJGLVHDVHV
FRQFRPLWDQWWKHUDS\RWKHUULVNIDFWRUVDQGWKHWHPSRUDOUHODWLRQVKLSRIWKH$(RU6$(WRWKH
VWXG\GUXJZLOOEHFRQVLGHUHGDQGLQYHVWLJDWHG7KHLQYHVWLJDWRUZLOODOVRFRQVXOWWKH,%
DQGRU3URGXFW,QIRUPDWLRQIRUPDUNHWHGSURGXFWVLQWKHGHWHUPLQDWLRQRIKLVKHU
DVVHVVPHQW
7KHUHPD\EHVLWXDWLRQVZKHQDQ6$(KDVRFFXUUHGDQGWKHLQYHVWLJDWRUKDVPLQLPDO
LQIRUPDWLRQWRLQFOXGHLQWKHLQLWLDOUHSRUWWRWKHVSRQVRU+RZHYHULWLVYHU\LPSRUWDQWWKDW
WKHLQYHVWLJDWRUDOZD\VPDNHVDVVHVVPHQWRIFDXVDOLW\IRUHYHU\6$(SULRUWRWUDQVPLVVLRQRI
WKH6$(UHSRUWH&5)WRWKHVSRQVRUVLQFHWKHFDXVDOLW\DVVHVVPHQWLVRQHRIWKHFULWHULDXVHG
ZKHQGHWHUPLQLQJUHJXODWRU\UHSRUWLQJUHTXLUHPHQWV7KHLQYHVWLJDWRUPD\FKDQJHKLV
RSLQLRQRIFDXVDOLW\LQOLJKWRIIROORZXSLQIRUPDWLRQDPHQGLQJWKH6$(UHSRUWH&5)
DFFRUGLQJO\
7KHFDXVDOLW\RIHDFK$(VKRXOGEHDVVHVVHGDQGFODVVLILHGE\WKHLQYHVWLJDWRUDV³UHODWHG´RU
³QRWUHODWHG´$Q$(LVFRQVLGHUHGUHODWHGLIWKHUHLV³DUHDVRQDEOHSRVVLELOLW\´WKDWWKH$(
PD\KDYHEHHQFDXVHGE\WKHVWXG\GUXJLHWKHUHDUHIDFWVHYLGHQFHRUDUJXPHQWVWR
VXJJHVWSRVVLEOHFDXVDWLRQ$QXPEHURIIDFWRUVVKRXOGEHFRQVLGHUHGLQPDNLQJWKLV
DVVHVVPHQWLQFOXGLQJ
x 7HPSRUDOUHODWLRQVKLSRIWKH$(WRWKHDGPLQLVWUDWLRQRIVWXG\WUHDWPHQWVWXG\
SURFHGXUH
x :KHWKHUDQDOWHUQDWLYHHWLRORJ\KDVEHHQLGHQWLILHG
x 0HFKDQLVPRIDFWLRQRIWKHVWXG\GUXJ
x %LRORJLFDOSODXVLELOLW\
$Q$(VKRXOGEHFRQVLGHUHG³UHODWHG´WRVWXG\GUXJLIDQ\RIWKHIROORZLQJDUHPHW
x 7KHUHLVFOHDUHYLGHQFHWRVXJJHVWDFDXVDOUHODWLRQVKLSDQGRWKHUSRVVLEOH
FRQWULEXWLQJIDFWRUVFDQEHUXOHGRXW
x 7KHUHLVHYLGHQFHWRVXJJHVWDFDXVDOUHODWLRQVKLSDQGWKHLQIOXHQFHRIRWKHUIDFWRUVLV
XQOLNHO\


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
x 7KHUHLVVRPHHYLGHQFHWRVXJJHVWDFDXVDOUHODWLRQVKLSHJWKH$(RFFXUUHGZLWKLQD
UHDVRQDEOHWLPHDIWHUDGPLQLVWUDWLRQRIWKHVWXG\GUXJ+RZHYHUWKHLQIOXHQFHRI
RWKHUIDFWRUVPD\KDYHFRQWULEXWHGWRWKH$(HJWKHVXEMHFW¶VFOLQLFDOFRQGLWLRQRU
RWKHUFRQFRPLWDQW$(V
$Q$(VKRXOGEHFRQVLGHUHG³XQUHODWHG´WRVWXG\GUXJLIDQ\RIWKHIROORZLQJDUHPHW
x $QXQUHDVRQDEOHWHPSRUDOUHODWLRQVKLSEHWZHHQDGPLQLVWUDWLRQRIWKHVWXG\GUXJDQG
WKHRQVHWRIWKH$(HJWKH$(RFFXUUHGHLWKHUEHIRUHRUWRRORQJDIWHUDGPLQLVWUDWLRQ
RIWKHSURGXFWIRULWWREHFRQVLGHUHGSURGXFWUHODWHG
x $FDXVDOUHODWLRQVKLSEHWZHHQWKHVWXG\GUXJDQGWKH$(LVELRORJLFDOO\LPSODXVLEOH
HJGHDWKDVDSDVVHQJHULQDQDXWRPRELOHDFFLGHQW
x $FOHDUO\PRUHOLNHO\DOWHUQDWLYHH[SODQDWLRQIRUWKH$(LVSUHVHQWHJW\SLFDODGYHUVH
UHDFWLRQWRDFRQFRPLWDQWGUXJDQGRUW\SLFDOGLVHDVHUHODWHG$(
 
)ROORZXSRI$GYHUVH(YHQWV
$IWHUWKHLQLWLDO$(RU6$(UHSRUWWKHLQYHVWLJDWRULVUHTXLUHGWRSURDFWLYHO\IROORZHDFK
VXEMHFWDQGSURYLGHIXUWKHULQIRUPDWLRQWRWKHVSRQVRURQWKHVXEMHFW¶VFRQGLWLRQ
$OO$(VDQG6$(VGRFXPHQWHGDWDSUHYLRXVYLVLWFRQWDFWDQGGHVLJQDWHGDVRQJRLQJZLOOEH
UHYLHZHGDWVXEVHTXHQWYLVLWVFRQWDFWV
$OO$(VDQG6$(VZLOOEHIROORZHGXQWLOUHVROXWLRQWKHFRQGLWLRQVWDELOL]HVRULVFRQVLGHUHG
FKURQLFRUQRWFOLQLFDOO\VLJQLILFDQWSHUWKHLQYHVWLJDWRUWKH$(RU6$(LVRWKHUZLVH
H[SODLQHGWKHVXEMHFWLVORVWWRIROORZXSRUWKHVXEMHFWZLWKGUDZVFRQVHQW2QFHUHVROYHG
WKHDSSURSULDWH$(RU6$(H&5)SDJHVZLOOEHXSGDWHG7KHLQYHVWLJDWRUZLOOHQVXUHWKDW
IROORZXSLQFOXGHVDQ\VXSSOHPHQWDOLQYHVWLJDWLRQVDVPD\EHLQGLFDWHGWRHOXFLGDWHWKH
QDWXUHDQGRUFDXVDOLW\RIWKH$(RU6$(7KLVPD\LQFOXGHDGGLWLRQDOODERUDWRU\WHVWVRU
LQYHVWLJDWLRQVKLVWRSDWKRORJLFDOH[DPLQDWLRQVRUFRQVXOWDWLRQZLWKRWKHUKHDOWKFDUH
SURIHVVLRQDOV
7KHVSRQVRUPD\UHTXHVWWKDWWKHLQYHVWLJDWRUSHUIRUPRUDUUDQJHIRUWKHFRQGXFWRI
VXSSOHPHQWDOPHDVXUHPHQWVDQGRUHYDOXDWLRQVWRHOXFLGDWHDVIXOO\DVSRVVLEOHWKHQDWXUH
DQGRUFDXVDOLW\RIWKH$(RU6$(7KHLQYHVWLJDWRULVREOLJDWHGWRDVVLVW,IDVXEMHFWGLHV
GXULQJSDUWLFLSDWLRQLQWKHVWXG\RUGXULQJDUHFRJQL]HGIROORZXSSHULRGWKHVSRQVRUZLOOEH
SURYLGHGZLWKDFRS\RIDQ\SRVWPRUWHPILQGLQJVLQFOXGLQJKLVWRSDWKRORJ\
1HZRUXSGDWHGLQIRUPDWLRQZLOOEHUHFRUGHGRQWKHRULJLQDOO\FRPSOHWHG6$(UHSRUWZLWK
DOOFKDQJHVVLJQHGDQGGDWHGE\WKHLQYHVWLJDWRU7KHXSGDWHG6$(UHSRUWVKRXOGEHUHVHQWWR
WKHVSRQVRUZLWKLQWKHWLPHIUDPHVRXWOLQHGLQ6HFWLRQ
 
/DERUDWRU\7HVW$EQRUPDOLWLHV
$EQRUPDOODERUDWRU\ILQGLQJVHJFOLQLFDOFKHPLVWU\FRPSOHWHEORRGFRXQWFRDJXODWLRQRU
XULQDO\VLVRURWKHUDEQRUPDODVVHVVPHQWVHJ(&*VRUYLWDOVLJQVWKDWDUHMXGJHGE\WKH
LQYHVWLJDWRUDVFOLQLFDOO\VLJQLILFDQWZLOOEHUHFRUGHGDV$(VRU6$(VLIWKH\PHHWWKH
GHILQLWLRQRIDQ$(DVGHILQHGLQ6HFWLRQRUDQ6$(DVGHILQHGLQ6HFWLRQ
&OLQLFDOO\VLJQLILFDQWDEQRUPDOODERUDWRU\ILQGLQJVRURWKHUDEQRUPDODVVHVVPHQWVWKDWDUH


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
GHWHFWHGGXULQJWKHVWXG\RUDUHSUHVHQWDWEDVHOLQHDQGVLJQLILFDQWO\ZRUVHQIROORZLQJWKH
VWDUWRIWKHVWXG\ZLOOEHUHSRUWHGDV$(VRU6$(V
7KHLQYHVWLJDWRUZLOOH[HUFLVHKLVPHGLFDODQGVFLHQWLILFMXGJPHQWLQGHFLGLQJZKHWKHUDQ
DEQRUPDOODERUDWRU\ILQGLQJRURWKHUDEQRUPDODVVHVVPHQWLVFOLQLFDOO\VLJQLILFDQW
 'HILQLWLRQRID6HULRXV$GYHUVH(YHQW
$Q6$(LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHWKDWDWDQ\GRVH
x 5HVXOWVLQGHDWK
x ,VOLIHWKUHDWHQLQJ
127(7KHWHUP³OLIHWKUHDWHQLQJ´LQWKHGHILQLWLRQRI³VHULRXV´UHIHUVWRDQ$(LQZKLFKWKH
VXEMHFWZDVDWULVNRIGHDWKDWWKHWLPHRIWKH$(,WGRHVQRWUHIHUWRDQ$(ZKLFK
K\SRWKHWLFDOO\PLJKWKDYHFDXVHGGHDWKLILWZHUHPRUHVHYHUH
x 5HTXLUHVKRVSLWDOL]DWLRQRUSURORQJDWLRQRIH[LVWLQJKRVSLWDOL]DWLRQ
127(,QJHQHUDOKRVSLWDOL]DWLRQVLJQLILHVWKDWWKHVXEMHFWZDVDGPLWWHGXVXDOO\LQYROYLQJ
DWOHDVWDQRYHUQLJKWVWD\WRWKHKRVSLWDORUHPHUJHQF\ZDUGIRUREVHUYDWLRQDQGRUWUHDWPHQW
WKDWZRXOGQRWKDYHEHHQDSSURSULDWHLQWKHSK\VLFLDQ¶VRIILFHRURXWSDWLHQWVHWWLQJ
&RPSOLFDWLRQVWKDWRFFXUGXULQJKRVSLWDOL]DWLRQDUH$(V,IDFRPSOLFDWLRQSURORQJV
KRVSLWDOL]DWLRQRUIXOILOOVDQ\RWKHUVHULRXVFULWHULDWKH$(LVVHULRXV:KHQLQGRXEWDVWR
ZKHWKHU³KRVSLWDOL]DWLRQ´RFFXUUHGRUZDVQHFHVVDU\WKH$(VKRXOGEHFRQVLGHUHGVHULRXV

7KHIROORZLQJDUH127FRQVLGHUHG6$(V
o +RVSLWDOL]DWLRQIRUHOHFWLYHWUHDWPHQWRIDSUHH[LVWLQJFRQGLWLRQWKDWGLGQRW
ZRUVHQIURPEDVHOLQHLVQRWFRQVLGHUHGDQ6$(
o +RVSLWDOL]DWLRQIRUVRFLDOFRQYHQLHQFHFRQVLGHUDWLRQVLVQRWFRQVLGHUHGDQ
6$(
o 6FKHGXOHGWKHUDS\IRUWKHWDUJHWGLVHDVHRIWKHVWXG\LQFOXGLQJDGPLVVLRQVIRU
WUDQVIXVLRQVXSSRUWRUFRQYHQLHQFH
x 5HVXOWVLQGLVDELOLW\LQFDSDFLW\
127(7KHWHUPGLVDELOLW\PHDQVDVXEVWDQWLDOGLVUXSWLRQRIDSHUVRQ¶VDELOLW\WRFRQGXFW
QRUPDOOLIHIXQFWLRQV7KLVGHILQLWLRQLVQRWLQWHQGHGWRLQFOXGHH[SHULHQFHVRIUHODWLYHO\
PLQRUPHGLFDOVLJQLILFDQFHVXFKDVXQFRPSOLFDWHGKHDGDFKHQDXVHDYRPLWLQJGLDUUKHD
LQIOXHQ]DDQGDFFLGHQWDOWUDXPDHJVSUDLQHGDQNOHZKLFKPD\LQWHUIHUHRUSUHYHQW
HYHU\GD\OLIHIXQFWLRQVEXWGRQRWFRQVWLWXWHDVXEVWDQWLDOGLVUXSWLRQ
x ,VDFRQJHQLWDODQRPDO\ELUWKGHIHFW
x ,VFRQVLGHUHGDVLJQLILFDQWPHGLFDO$(E\WKHLQYHVWLJDWRUEDVHGRQPHGLFDOMXGJPHQW
HJPD\MHRSDUGL]HWKHVXEMHFWRUPD\UHTXLUHPHGLFDOVXUJLFDOLQWHUYHQWLRQWR
SUHYHQWRQHRIWKHRXWFRPHVOLVWHGDERYH


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 6XVSHFWHG8QH[SHFWHG6HULRXV$GYHUVH5HDFWLRQ
$VXVSHFWHGXQH[SHFWHGVHULRXVDGYHUVHUHDFWLRQLVDVHULRXVDGYHUVHUHDFWLRQWKDWLVERWK
XQH[SHFWHGLHQRWSUHVHQWLQWKHSURGXFW¶V5HIHUHQFH6DIHW\,QIRUPDWLRQDQGPHHWVWKH
GHILQLWLRQRIDVHULRXVDGYHUVHGUXJUHDFWLRQWKHVSHFLILFLW\RUVHYHULW\RIZKLFKLVQRW
FRQVLVWHQWZLWKWKRVHQRWHGLQWKH,%
 7LPLQJ)UHTXHQF\DQG0HWKRGRI&DSWXULQJ$GYHUVH(YHQWVDQG6HULRXV
$GYHUVH(YHQWV
 
$GYHUVH(YHQW5HSRUWLQJ3HULRG
$IWHULQIRUPHGFRQVHQWKDVEHHQVLJQHGEXWSULRUWRWKHDGPLQLVWUDWLRQRIWKHVWXG\GUXJRQO\
6$(VVKRXOGEHUHSRUWHG
$IWHULQLWLDWLRQRIVWXG\GUXJDOO$(VDQG6$(VUHJDUGOHVVRIUHODWLRQVKLSWRVWXG\GUXJZLOO
EHUHSRUWHGXQWLOGD\VDIWHUWKHODVWVWXG\WUHDWPHQWRIVWXG\GUXJ$IWHUWKLVSHULRGWKH
LQYHVWLJDWRUVKRXOGUHSRUWDQ\6$(VWKDWDUHEHOLHYHGWREHUHODWHGWRSULRUVWXG\GUXJ
WUHDWPHQW
 
(OLFLWLQJ5HVSRQVHV$ERXW$GYHUVH(YHQWV
7KHLQYHVWLJDWRURUGHVLJQHHZLOODVNDERXW$(VE\DVNLQJWKHIROORZLQJVWDQGDUGTXHVWLRQV
x +RZGR\RXIHHO"
x $Q\FKDQJHLQ\RXUKHDOWKVLQFH\RXUODVWYLVLW"
x +DYH\RXWDNHQDQ\QHZPHGLFDWLRQVVLQFH\RXUODVWYLVLW"
 6SHFLILF,QVWUXFWLRQVIRU5HFRUGLQJ$GYHUVH(YHQWVDQG6HULRXV$GYHUVH(YHQWV
 
'HDWK
:KHQUHFRUGLQJDGHDWKDVDQ6$(WKH$(WKDWFDXVHGRUFRQWULEXWHGWRWKHIDWDORXWFRPH
VKRXOGEHUHFRUGHGDVWKHVLQJOHPHGLFDOFRQFHSW,IWKHFDXVHRIGHDWKLVXQNQRZQDQG
FDQQRWEHDVFHUWDLQHGDWWKHWLPHRIUHSRUWLQJUHFRUG³XQH[SODLQHGGHDWK´
 3URPSW5HSRUWLQJRI6HULRXV$GYHUVH(YHQWV
 
7LPHIUDPHVIRU6XEPLWWLQJ6HULRXV$GYHUVH(YHQWV
6HULRXV$(VZLOOEHUHSRUWHGZLWKLQKRXUVRIILUVWNQRZOHGJHRIWKH6$(WRWKHVSRQVRURU
GHVLJQHHDVGHVFULEHGLQ7DEOHRQFHWKHLQYHVWLJDWRUGHWHUPLQHVWKDWWKH$(PHHWVWKH
SURWRFROGHILQLWLRQRIDQ6$(


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
7DEOH
7LPHIUDPHVDQG'RFXPHQWDWLRQ0HWKRGVIRU5HSRUWLQJ6HULRXV$GYHUVH
(YHQWVWRWKH6SRQVRURU'HVLJQHH

7LPHIUDPHIRU
0DNLQJ,QLWLDO
5HSRUW
'RFXPHQWDWLRQ
0HWKRG
7LPHIUDPH
IRU0DNLQJ
)ROORZXS
5HSRUW
'RFXPHQWDWLRQ
0HWKRG
5HSRUWLQJ
0HWKRG
$OO6$(V
:LWKLQ
KRXUVRIILUVW
NQRZOHGJHRI
WKH6$(
6$(5HSRUW
$V
H[SHGLWLRXVO\
DVSRVVLEOH
6$(5HSRUW

(PDLORUID[
6$(IRUP
$EEUHYLDWLRQ6$( VHULRXVDGYHUVHHYHQW
 
&RPSOHWLRQDQG7UDQVPLVVLRQRIWKH6HULRXV$GYHUVH(YHQW5HSRUW
2QFHDQLQYHVWLJDWRUEHFRPHVDZDUHWKDWDQ6$(KDVRFFXUUHGLQDVXEMHFWKHLVWRUHSRUWWKH
LQIRUPDWLRQWRWKHVSRQVRUZLWKLQKRXUVDVRXWOLQHGDERYHLQ6HFWLRQ7KH6$(
5HSRUWZLOODOZD\VEHFRPSOHWHGDVWKRURXJKO\DVSRVVLEOHZLWKDOODYDLODEOHGHWDLOVRIWKH
HYHQWDQGIRUZDUGHGWRWKHVSRQVRURUGHVLJQHHZLWKLQWKHGHVLJQDWHGWLPHIUDPHV
,IWKHLQYHVWLJDWRUGRHVQRWKDYHDOOLQIRUPDWLRQUHJDUGLQJDQ6$(KHLVQRWWRZDLWWRUHFHLYH
DGGLWLRQDOLQIRUPDWLRQEHIRUHQRWLI\LQJWKHVSRQVRURUGHVLJQHHRIWKH6$(DQGFRPSOHWLQJ
WKHIRUP7KHIRUPZLOOEHXSGDWHGZKHQDGGLWLRQDOLQIRUPDWLRQLVUHFHLYHG
7KHLQYHVWLJDWRUPXVWDOZD\VSURYLGHDQDVVHVVPHQWRIFDXVDOLW\IRUHDFK6$(DVGHVFULEHG
LQ6HFWLRQ
7KHVSRQVRUZLOOSURYLGHFRQWDFWLQIRUPDWLRQIRU6$(UHFHLSW
 
5HJXODWRU\5HSRUWLQJ5HTXLUHPHQWVIRU6HULRXV$GYHUVH(YHQWV
7KHLQYHVWLJDWRUZLOOSURPSWO\UHSRUWDOO6$(VWRWKHVSRQVRULQDFFRUGDQFHZLWKWKH
SURFHGXUHVGHWDLOHGLQ6HFWLRQ7KHVSRQVRUKDVDOHJDOUHVSRQVLELOLW\WRQRWLI\DV
DSSURSULDWHERWKWKHORFDOUHJXODWRU\DXWKRULW\DQGRWKHUUHJXODWRU\DJHQFLHVDERXWWKHVDIHW\
RIDSURGXFWXQGHUFOLQLFDOLQYHVWLJDWLRQ
7KHLQYHVWLJDWRURUUHVSRQVLEOHSHUVRQDFFRUGLQJWRORFDOUHTXLUHPHQWVZLOOFRPSO\ZLWKWKH
DSSOLFDEOHORFDOUHJXODWRU\UHTXLUHPHQWVUHODWHGWRWKHUHSRUWLQJRI6$(VWRUHJXODWRU\
DXWKRULWLHVDQGWKH,QVWLWXWLRQDO5HYLHZ%RDUG,5%
$OOVXVSHFWHGXQH[SHFWHGVHULRXVDGYHUVHUHDFWLRQVDVGHILQHGLQ6HFWLRQZLOOEH
VXEPLWWHGWRDOODSSOLFDEOHUHJXODWRU\DXWKRULWLHVDQGLQYHVWLJDWRUVIRU]DQXEUXWLQLEVWXGLHV

:KHQDVWXG\FHQWHUUHFHLYHVDQLQLWLDORUIROORZXSUHSRUWRURWKHUVDIHW\LQIRUPDWLRQHJ
UHYLVHG,%IURPWKHVSRQVRUWKHUHVSRQVLEOHSHUVRQDFFRUGLQJWRORFDOUHTXLUHPHQWVLV
UHTXLUHGWRSURPSWO\QRWLI\KLVKHU,5%7KHLQYHVWLJDWRUVKRXOGSODFHFRSLHVRI6DIHW\
5HSRUWVIURPWKHVSRQVRULQWKH,QYHVWLJDWRU6LWH)LOH


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
 3UHJQDQF\5HSRUWLQJ
,IWKHSDUWQHURIDPDOHVXEMHFWEHFRPHVSUHJQDQWZLWKLQGD\VDIWHUWKHFRPSOHWLRQRIWKH
ODVWGRVHRIVWXG\GUXJDSUHJQDQF\UHSRUWIRUPVKRXOGEHFRPSOHWHGDQGH[SHGLWLRXVO\
VXEPLWWHGWRWKHVSRQVRUWRIDFLOLWDWHRXWFRPHIROORZXS,QIRUPDWLRQRQWKHVWDWXVRIWKH
PRWKHUDQGFKLOGZLOOEHIRUZDUGHGWRWKHVSRQVRU*HQHUDOO\IROORZXSZLOOEHQRORQJHU
WKDQWRZHHNVIROORZLQJWKHHVWLPDWHGGHOLYHU\GDWH$Q\SUHPDWXUHWHUPLQDWLRQRIWKH
SUHJQDQF\ZLOOEHUHSRUWHG
:KLOHSUHJQDQF\LWVHOILVQRWFRQVLGHUHGWREHDQ$(RU6$(DQ\SUHJQDQF\FRPSOLFDWLRQRU
HOHFWLYHWHUPLQDWLRQRIDSUHJQDQF\IRUPHGLFDOUHDVRQVZLOOEHUHFRUGHGDVDQ$(RU6$(
$QDERUWLRQZKHWKHUDFFLGHQWDOWKHUDSHXWLFRUVSRQWDQHRXVVKRXOGDOZD\VEHUHSRUWHGDVDQ
6$(6LPLODUO\DQ\FRQJHQLWDODQRPDO\ELUWKGHIHFWLQDFKLOGERUQWRDVXEMHFWH[SRVHGWR
WKHVWXG\GUXJVKRXOGEHUHFRUGHGDQGUHSRUWHGDVDQ6$(
 ([SHGLWHG5HSRUWLQJWR+HDOWK$XWKRULWLHV,QYHVWLJDWRUVDQG,QVWLWXWLRQDO
5HYLHZ%RDUGV
7KHVSRQVRUZLOOSURPSWO\DVVHVVDOO6$(VDJDLQVWFXPXODWLYHVWXG\GUXJH[SHULHQFHWR
LGHQWLI\DQGH[SHGLWLRXVO\FRPPXQLFDWHQHZVDIHW\ILQGLQJVWRUHJXODWRU\DXWKRULWLHV
LQYHVWLJDWRUVDQG,5%VEDVHGRQDSSOLFDEOHOHJLVODWLRQ
7RGHWHUPLQHWKHUHSRUWLQJUHTXLUHPHQWVIRULQGLYLGXDO6$(VWKHVSRQVRUZLOODVVHVVWKH
H[SHFWHGQHVVRIWKH6$(VXVLQJWKHIROORZLQJUHIHUHQFHGRFXPHQWV
x =DQXEUXWLQLE%*%,%
x /RFDOSUHVFULELQJLQIRUPDWLRQIRUULIDEXWLQ




3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
$SSHQGL[&OLQLFDO/DERUDWRU\(YDOXDWLRQV
&OLQLFDOFKHPLVWU\
+HPDWRORJ\
8ULQDO\VLV
$ODQLQHDPLQRWUDQVIHUDVH
$OEXPLQ
$ONDOLQHSKRVSKDWDVH
$VSDUWDWHDPLQRWUDQVIHUDVH
%LFDUERQDWH
%ORRGXUHDQLWURJHQ
&DOFLXP
&KORULGH
&KROHVWHURO
&UHDWLQLQH
*DPPDJOXWDP\OWUDQVIHUDVH
*OXFRVH
/LSDVH
3RWDVVLXP
6RGLXP
7RWDOELOLUXELQD
7RWDOSURWHLQ
8ULFDFLG
+HPDWRFULW
+HPRJORELQ
0HDQFHOOKHPRJORELQ
0HDQFHOOKHPRJORELQ
FRQFHQWUDWLRQ
0HDQFHOOYROXPH
3ODWHOHWFRXQW
5HGEORRGFHOO5%&FRXQW
5%&GLVWULEXWLRQZLGWK
:KLWHEORRGFHOO:%&FRXQW
:%&GLIIHUHQWLDO
%DVRSKLOV
(RVLQRSKLOV
/\PSKRF\WHV
0RQRF\WHV
1HXWURSKLOV

%LOLUXELQ
%ORRG
&RORUDQGDSSHDUDQFH
*OXFRVH
.HWRQHV
/HXNRF\WHHVWHUDVH
1LWULWH
S+
3URWHLQ
6SHFLILFJUDYLW\
8URELOLQRJHQ
0LFURVFRSLFH[DPLQDWLRQLI
SURWHLQOHXNRF\WHHVWHUDVHQLWULWH
RUEORRGLVSRVLWLYH

6HURORJ\E
'UXJVFUHHQF
2WKHUWHVWE
$QWLKHSDWLWLV%VXUIDFHDQWLERG\
$QWLKHSDWLWLV%FRUHDQWLERG\
+HSDWLWLV%VXUIDFHDQWLJHQ
+HSDWLWLV&DQWLERG\
+XPDQLPPXQRGHILFLHQF\YLUXV
+,9DQG+,9DQWLERGLHV
DQGSDQWLJHQ
,QFOXGLQJEXWQRWOLPLWHGWR
$PSKHWDPLQHVPHWKDPSKHWDPLQHV
%DUELWXUDWHV
%HQ]RGLD]HSLQHV
&RFDLQHPHWDEROLWH
0HWKDGRQH
3KHQF\FOLGLQH
2SLDWHV
7HWUDK\GURFDQQDELQRO
FDQQDELQRLGV
&RWLQLQHWHVW
$OFRKROWHVWG
7XEHUFXORVLVWHVW
D'LUHFWDQGLQGLUHFWELOLUXELQZLOOEHDQDO\]HGLIWRWDOELOLUXELQLVHOHYDWHG
E2QO\DQDO\]HGDWVFUHHQLQJ
F2QO\DQDO\]HGDWVFUHHQLQJDQGFKHFNLQ
G2QO\DQDO\]HGDWFKHFNLQDOFRKROWHVWPD\EHXULQHEUHDWKRUEORRGWHVW


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
$SSHQGL[7RWDO%ORRG9ROXPH
7KHIROORZLQJEORRGYROXPHVZLOOEHZLWKGUDZQIRUHDFKVXEMHFW

9ROXPHSHUEORRG
VDPSOHP/
0D[LPXPQXPEHURI
EORRGVDPSOHV
7RWDODPRXQWRI
EORRGP/
&OLQLFDOODERUDWRU\
HYDOXDWLRQV



6HURORJ\



7XEHUFXORVLVWHVW



=DQXEUXWLQLE
SKDUPDFRNLQHWLFV



7RWDO

,IH[WUDEORRGVDPSOHVDUHUHTXLUHGWKHPD[LPXPEORRGYROXPHWREHZLWKGUDZQSHUVXEMHFW
ZLOOQRWH[FHHGP/


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
$SSHQGL[5HJXODWRU\(WKLFDODQG6WXG\2YHUVLJKW&RQVLGHUDWLRQV
5HJXODWRU\DQG(WKLFDO&RQVLGHUDWLRQV
7KLVVWXG\ZLOOEHFRQGXFWHGLQDFFRUGDQFHZLWKWKHSURWRFRODQGZLWKWKHIROORZLQJ
x &RQVHQVXVHWKLFDOSULQFLSOHVGHULYHGIURPLQWHUQDWLRQDOJXLGHOLQHVLQFOXGLQJWKH
'HFODUDWLRQRI+HOVLQNLDQG&RXQFLOIRU,QWHUQDWLRQDO2UJDQL]DWLRQVRI0HGLFDO
6FLHQFHV&,206,QWHUQDWLRQDO(WKLFDO*XLGHOLQHV
x $SSOLFDEOH,QWHUQDWLRQDO&RQIHUHQFHRQ+DUPRQLVDWLRQ,&+*RRG&OLQLFDO3UDFWLFH
*&3*XLGHOLQHV
x $SSOLFDEOHODZVDQGUHJXODWLRQV
7KHSURWRFROSURWRFRODPHQGPHQWV,&),%DQGRWKHUUHOHYDQWGRFXPHQWVHJ
DGYHUWLVHPHQWVPXVWEHVXEPLWWHGWRDQ,5%E\WKHLQYHVWLJDWRUDQGUHYLHZHGDQGDSSURYHG
E\WKH,5%EHIRUHWKHVWXG\LVLQLWLDWHG
$Q\DPHQGPHQWVWRWKHSURWRFROZLOOUHTXLUH,5%DQGUHJXODWRU\DXWKRULW\DVORFDOO\
UHTXLUHGDSSURYDOEHIRUHLPSOHPHQWDWLRQRIFKDQJHVPDGHWRWKHVWXG\GHVLJQH[FHSWIRU
FKDQJHVQHFHVVDU\WRHOLPLQDWHDQLPPHGLDWHKD]DUGWRVWXG\VXEMHFWV
7KHLQYHVWLJDWRUZLOOEHUHVSRQVLEOHIRUWKHIROORZLQJ
x 3URYLGLQJZULWWHQVXPPDULHVRIWKHVWDWXVRIWKHVWXG\WRWKH,5%DQQXDOO\RUPRUH
IUHTXHQWO\LQDFFRUGDQFHZLWKWKHUHTXLUHPHQWVSROLFLHVDQGSURFHGXUHVHVWDEOLVKHG
E\WKH,5%
x 1RWLI\LQJWKH,5%RI6$(VRURWKHUVLJQLILFDQWVDIHW\ILQGLQJVDVUHTXLUHGE\,5%
SURFHGXUHV
x 3URYLGLQJRYHUVLJKWRIWKHFRQGXFWRIWKHVWXG\DWWKHVLWHDQGDGKHUHQFHWR
UHTXLUHPHQWVRI&RGHRI)HGHUDO5HJXODWLRQV&)5,&+JXLGHOLQHVWKH,5%
(XURSHDQ'LUHFWLYH(&IRUFOLQLFDOVWXGLHVLIDSSOLFDEOHDQGDOORWKHU
DSSOLFDEOHORFDOUHJXODWLRQV
)LQDQFHVDQG,QVXUDQFH
)LQDQFLQJDQGLQVXUDQFHZLOOEHDGGUHVVHGLQDVHSDUDWHDJUHHPHQW
,QIRUPHG&RQVHQW
3ULRUWRVWDUWLQJSDUWLFLSDWLRQLQWKHVWXG\HDFKVXEMHFWZLOOEHSURYLGHGZLWKDVWXG\VSHFLILF
,&)JLYLQJGHWDLOVRIWKHVWXG\WUHDWPHQWVSURFHGXUHVDQGSRWHQWLDOULVNVRIWKHVWXG\
6XEMHFWVZLOOEHLQVWUXFWHGWKDWWKH\DUHIUHHWRREWDLQIXUWKHULQIRUPDWLRQIURPWKH
LQYHVWLJDWRURUGHVLJQHHDQGWKDWWKHLUSDUWLFLSDWLRQLVYROXQWDU\DQGWKH\DUHIUHHWR
ZLWKGUDZIURPWKHVWXG\DWDQ\WLPH6XEMHFWVZLOOEHJLYHQDQRSSRUWXQLW\WRDVNTXHVWLRQV
DERXWWKHVWXG\SULRUWRSURYLGLQJFRQVHQWIRUSDUWLFLSDWLRQ
)ROORZLQJGLVFXVVLRQRIWKHVWXG\ZLWK&58SHUVRQQHOVXEMHFWVZLOOVLJQFRSLHVRIWKH,&)
LQWKHSUHVHQFHRIDVXLWDEO\WUDLQHGPHPEHURIVWDIIWRLQGLFDWHWKDWWKH\DUHIUHHO\JLYLQJ


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
WKHLULQIRUPHGFRQVHQW2QHFRS\ZLOOEHJLYHQWRWKHVXEMHFWDQGWKHRWKHUZLOOEH
PDLQWDLQHGLQWKHVXEMHFW¶VUHFRUGV
6XEMHFWVPXVWEHUHFRQVHQWHGWRWKHPRVWFXUUHQWYHUVLRQRIWKH,&)VGXULQJWKHLU
SDUWLFLSDWLRQLQWKHVWXG\
6XEMHFW'DWD3URWHFWLRQ
6XEMHFWVZLOOEHDVVLJQHGDXQLTXHLGHQWLILHUDQGZLOOQRWEHLGHQWLILHGE\QDPHLQH&5)V
VWXG\UHODWHGIRUPVVWXG\UHSRUWVRUDQ\UHODWHGSXEOLFDWLRQV6XEMHFWDQGLQYHVWLJDWRU
SHUVRQDOGDWDZLOOEHWUHDWHGLQFRPSOLDQFHZLWKDOODSSOLFDEOHODZVDQGUHJXODWLRQV,QWKH
HYHQWWKHVWXG\SURWRFROVWXG\UHSRUWRUVWXG\GDWDDUHLQFOXGHGLQDSXEOLFUHJLVWU\DOO
LGHQWLILDEOHLQIRUPDWLRQIURPLQGLYLGXDOVXEMHFWVRULQYHVWLJDWRUZLOOEHUHGDFWHGDFFRUGLQJWR
DSSOLFDEOHODZVDQGUHJXODWLRQV
7KHVXEMHFWPXVWEHLQIRUPHGWKDWKLVSHUVRQDOVWXG\UHODWHGGDWDZLOOEHXVHGE\WKHVSRQVRU
LQDFFRUGDQFHZLWKORFDOGDWDSURWHFWLRQODZ7KHOHYHORIGLVFORVXUHPXVWDOVREHH[SODLQHG
WRWKHVXEMHFW7KHVXEMHFWPXVWDOVREHLQIRUPHGWKDWKLVVWXG\UHODWHGGDWDPD\EHH[DPLQHG
E\VSRQVRURUFRQWUDFWUHVHDUFKRUJDQL]DWLRQ&52DXGLWRUVRURWKHUDXWKRUL]HGSHUVRQQHO
DSSRLQWHGE\WKHVSRQVRUE\DSSURSULDWH,5%PHPEHUVDQGE\LQVSHFWRUVIURPUHJXODWRU\
DXWKRULWLHV
'LVFORVXUH
$OOLQIRUPDWLRQSURYLGHGUHJDUGLQJWKHVWXG\LQFOXGLQJEXWQRWOLPLWHGWRWKH,%WKLV
SURWRFROH&5)VWKHLQYHVWLJDWLRQDOGUXJDQGDQ\RWKHUVWXG\LQIRUPDWLRQDVZHOODVDOO
LQIRUPDWLRQFROOHFWHGDQGRUGRFXPHQWHGGXULQJWKHFRXUVHRIWKHVWXG\LVDQGUHPDLQVWKH
VROHDQGH[FOXVLYHSURSHUW\RIWKHVSRQVRUDQGZLOOEHUHJDUGHGDVFRQILGHQWLDOGXULQJWKH
FRQGXFWRIWKHVWXG\DQGWKHUHDIWHU7KHLQYHVWLJDWRURUGHVLJQHHDJUHHVQRWWRGLVFORVHVXFK
LQIRUPDWLRQLQDQ\ZD\WRDQ\WKLUGSDUW\H[FHSWHPSOR\HHVRUDJHQWVGLUHFWO\LQYROYHGLQ
WKHFRQGXFWRIWKHVWXG\RUDVUHTXLUHGE\ODZZLWKRXWSULRUZULWWHQSHUPLVVLRQIURPWKH
VSRQVRUDQGVKDOOWDNHDOOUHDVRQDEOHSUHFDXWLRQVWRSUHYHQWDQ\XQDXWKRUL]HGGLVFORVXUHE\
DQ\HPSOR\HHRUDJHQWRIWKHVWXG\VLWH
0RQLWRULQJ
,QDFFRUGDQFHZLWKDSSOLFDEOHUHJXODWLRQV*&3DQGVSRQVRUSURFHGXUHVWKHVSRQVRUKDV
HQJDJHGWKHVHUYLFHVRID&52WRSHUIRUPDOOPRQLWRULQJIXQFWLRQVZLWKLQWKLVFOLQLFDOVWXG\
0RQLWRUVZLOOZRUNLQDFFRUGDQFHZLWKWKHVSRQVRURU&52VWDQGDUGRSHUDWLQJSURFHGXUHV
623VDQGKDYHWKHVDPHULJKWVDQGUHVSRQVLELOLWLHVDVPRQLWRUVIURPWKHVSRQVRU¶V
RUJDQL]DWLRQ0RQLWRUVZLOOHVWDEOLVKDQGPDLQWDLQUHJXODUFRQWDFWEHWZHHQWKHLQYHVWLJDWRU
DQGWKHVSRQVRU
'XULQJWKHVHFRQWDFWVWKHPRQLWRUZLOO
x &KHFNWKHSURJUHVVRIWKHVWXG\
x 5HYLHZVWXG\GDWDFROOHFWHG
x &RQGXFWVRXUFHGRFXPHQWYHULILFDWLRQ


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
x ,GHQWLI\DQ\LVVXHVDQGDGGUHVVWKHLUUHVROXWLRQ
7KLVZLOOEHGRQHLQRUGHUWRYHULI\WKDWWKH
x 'DWDDUHDXWKHQWLFDFFXUDWHDQGFRPSOHWH
x 6DIHW\DQGULJKWVRIVXEMHFWVDUHEHLQJSURWHFWHG
x 6WXG\LVFRQGXFWHGLQDFFRUGDQFHZLWKWKHFXUUHQWO\DSSURYHGSURWRFRODQGDQ\
DPHQGPHQWV*&3DQGDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV
7KHLQYHVWLJDWRUDJUHHVWRDOORZWKHPRQLWRUGLUHFWDFFHVVWRDOOUHOHYDQWGRFXPHQWVDQGWR
DOORFDWHKLVWLPHDQGWKHWLPHRIKLVSHUVRQQHOWRWKHPRQLWRUWRGLVFXVVILQGLQJVDQGDQ\
UHOHYDQWLVVXHV
'DWD0DQDJHPHQW&RGLQJ
'DWDJHQHUDWHGZLWKLQWKLVFOLQLFDOVWXG\ZLOOEHKDQGOHGDFFRUGLQJWRWKHUHOHYDQW623VRI
WKHGDWDPDQDJHPHQWGHSDUWPHQWRIWKH&52
$QHOHFWURQLFGDWDFDSWXUH('&V\VWHPZLOOEHXVHGIRUWKLVVWXG\PHDQLQJWKDWDOOH&5)
GDWDZLOOEHHQWHUHGLQHOHFWURQLFIRUPVDWWKHVWXG\FHQWHU'DWDFROOHFWLRQZLOOEHFRPSOHWHG
E\DXWKRUL]HGVWXG\FHQWHUSHUVRQQHOGHVLJQDWHGE\WKHLQYHVWLJDWRU$SSURSULDWHWUDLQLQJDQG
VHFXULW\PHDVXUHVZLOOEHFRPSOHWHGZLWKWKHLQYHVWLJDWRUDQGDOODXWKRUL]HGVWXG\FHQWHU
SHUVRQQHOSULRUWRWKHVWXG\EHLQJLQLWLDWHGDQGSULRUWRDQ\GDWDEHLQJHQWHUHGLQWRWKHV\VWHP
IRUDQ\VXEMHFWV
7KHH&5)VVKRXOGDOZD\VUHIOHFWWKHODWHVWREVHUYDWLRQVRIWKHVXEMHFWVSDUWLFLSDWLQJLQWKH
VWXG\7KHUHIRUHWKHH&5)VDUHWREHFRPSOHWHGDVVRRQDVSRVVLEOHGXULQJRUDIWHUWKH
VXEMHFW¶VYLVLW,IVRPHDVVHVVPHQWVDUHQRWGRQHRULIFHUWDLQLQIRUPDWLRQLVQRWDYDLODEOHRU
QRWDSSOLFDEOHRUXQNQRZQWKHLQYHVWLJDWRURUGHVLJQHHVKRXOGLQGLFDWHWKLVLQWKHH&5)
7KHLQYHVWLJDWRUZLOOEHUHTXLUHGWRHOHFWURQLFDOO\VLJQRIIRQWKHFOLQLFDOGDWDRQFHFRPSOHWH
7KHPRQLWRUZLOOUHYLHZWKHH&5)VDQGHYDOXDWHWKHPIRUFRPSOHWHQHVVDQGFRQVLVWHQF\7KH
H&5)ZLOOEHFRPSDUHGZLWKWKHVRXUFHGRFXPHQWVWRHQVXUHWKDWWKHUHDUHQRGLVFUHSDQFLHV
EHWZHHQFULWLFDOGDWD$OOHQWULHVFRUUHFWLRQVDQGDOWHUDWLRQVDUHWREHPDGHE\WKH
UHVSRQVLEOHLQYHVWLJDWRURUKLVGHVLJQHH7KHPRQLWRUFDQQRWHQWHUGDWDLQWKHH&5)V2QFH
FOLQLFDOGDWDKDYHEHHQHQWHUHGLQWRWKHH&5)DQ\FRUUHFWLRQVRUDOWHUDWLRQVWRWKHGDWDILHOGV
ZLOOEHWUDFHDEOHYLDDQDXGLWWUDLOPHDQLQJWKDWWKHUHDVRQIRUFKDQJHWKHQDPHRIWKHSHUVRQ
ZKRSHUIRUPHGWKHFKDQJHWRJHWKHUZLWKWLPHDQGGDWHZLOOEHORJJHG5ROHVDQGULJKWVRI
WKHVWXG\FHQWHUSHUVRQQHOUHVSRQVLEOHIRUHQWHULQJWKHFOLQLFDOGDWDLQWRWKHH&5)ZLOOEH
GHWHUPLQHGLQDGYDQFH,IDGGLWLRQDOFRUUHFWLRQVDUHQHHGHGWKHUHVSRQVLEOHPRQLWRURUGDWD
PDQDJHUZLOOUDLVHDTXHU\LQWKH('&DSSOLFDWLRQ7KHDSSURSULDWHVWXG\FHQWHUSHUVRQQHO
ZLOOUHVSRQGWRDQ\UDLVHGTXHULHV
7KHH&5)LVHVVHQWLDOO\FRQVLGHUHGDGDWDHQWU\IRUPDQGVKRXOGQRWFRQVWLWXWHWKHRULJLQDO
RUVRXUFHPHGLFDOUHFRUGVXQOHVVRWKHUZLVHVSHFLILHG6RXUFHGRFXPHQWVDUHDOOGRFXPHQWV
XVHGE\WKHLQYHVWLJDWRURUKRVSLWDOWKDWUHODWHWRWKHVXEMHFW¶VPHGLFDOKLVWRU\WKDWYHULI\WKH
H[LVWHQFHRIWKHVXEMHFWWKHLQFOXVLRQDQGH[FOXVLRQFULWHULDDQGDOOUHFRUGVFRYHULQJWKH
VXEMHFW¶VSDUWLFLSDWLRQLQWKHVWXG\7KH\LQFOXGHODERUDWRU\QRWHV(&*UHVXOWVPHPRUDQGD
SKDUPDF\GLVSHQVLQJUHFRUGVVXEMHFWILOHVHWF


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
7KHLQYHVWLJDWRULVUHVSRQVLEOHIRUPDLQWDLQLQJVRXUFHGRFXPHQWV7KHVHZLOOEHPDGH
DYDLODEOHIRULQVSHFWLRQE\WKHVWXG\PRQLWRUDWHDFKPRQLWRULQJYLVLW7KHLQYHVWLJDWRUPXVW
VXEPLWDFRPSOHWHGH&5)IRUHDFKVXEMHFWZKRUHFHLYHVWKHLQYHVWLJDWLRQDOSURGXFWV
UHJDUGOHVVRIWKHGXUDWLRQ$OOVXSSRUWLYHGRFXPHQWDWLRQVXEPLWWHGZLWKWKHH&5)VXFKDV
ODERUDWRU\RUKRVSLWDOUHFRUGVVKRXOGEHFOHDUO\LGHQWLILHGZLWKWKHVWXG\DQGVXEMHFWQXPEHU
$Q\SHUVRQDOLQIRUPDWLRQLQFOXGLQJVXEMHFWQDPHVKRXOGEHUHPRYHGRUUHQGHUHGLOOHJLEOHWR
SUHVHUYHLQGLYLGXDOFRQILGHQWLDOLW\
(OHFWURQLFFDVHUHSRUWIRUPUHFRUGVZLOOEHDXWRPDWLFDOO\DSSHQGHGZLWKWKHLGHQWLILFDWLRQRI
WKHFUHDWRUE\PHDQVRIWKHLUXQLTXHXVHULGHQWLILFDWLRQ6SHFLILHGUHFRUGVZLOOEH
HOHFWURQLFDOO\VLJQHGE\WKHLQYHVWLJDWRUWRGRFXPHQWKLVUHYLHZRIWKHGDWDDQG
DFNQRZOHGJPHQWWKDWWKHGDWDDUHDFFXUDWH7KLVZLOOEHIDFLOLWDWHGE\PHDQVRIWKH
LQYHVWLJDWRU¶VXQLTXHXVHULGHQWLILFDWLRQDQGSDVVZRUGGDWHDQGWLPHVWDPSVZLOOEHDGGHG
DXWRPDWLFDOO\DWWKHWLPHRIWKHHOHFWURQLFVLJQDWXUH,IDQHQWU\RQDQH&5)UHTXLUHVFKDQJH
WKHFRUUHFWLRQVKRXOGEHPDGHLQDFFRUGDQFHZLWKWKHUHOHYDQWVRIWZDUHSURFHGXUHV$OO
FKDQJHVZLOOEHIXOO\UHFRUGHGLQDSURWHFWHGDXGLWWUDLODQGDUHDVRQIRUWKHFKDQJHZLOOEH
UHTXLUHG
$GYHUVHHYHQWVZLOOEHFRGHGXVLQJWKH0HG'5$9HUVLRQRUKLJKHU&RQFRPLWDQW
PHGLFDWLRQVZLOOEHFRGHGXVLQJWKH:RUOG+HDOWK2UJDQL]DWLRQ'UXJ'LFWLRQDU\
&RQFRPLWDQWGLVHDVHVPHGLFDOKLVWRU\ZLOOEHFRGHGXVLQJWKH0HG'5$9HUVLRQRU
KLJKHU
4XDOLW\$VVXUDQFH$XGLW
7RHQVXUHFRPSOLDQFHZLWK*&3DQGDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWVWKHVSRQVRUPD\
FRQGXFWDTXDOLW\DVVXUDQFHDXGLW5HJXODWRU\DJHQFLHVPD\DOVRFRQGXFWDUHJXODWRU\
LQVSHFWLRQRIWKLVVWXG\6XFKDXGLWVLQVSHFWLRQVFDQRFFXUDWDQ\WLPHGXULQJRUDIWHU
FRPSOHWLRQRIWKHVWXG\,IDQDXGLWRULQVSHFWLRQRFFXUVWKHLQYHVWLJDWRUDQGLQVWLWXWLRQDJUHH
WRDOORZWKHDXGLWRULQVSHFWRUGLUHFWDFFHVVWRDOOUHOHYDQWGRFXPHQWVDQGWKHIDFLOLWLHVXVHG
IRUWKLVWULDODQGWRDOORFDWHKLVWLPHDQGWKHWLPHRIKLVSHUVRQQHOWRWKHDXGLWRULQVSHFWRUWR
GLVFXVVILQGLQJVDQGDQ\UHOHYDQWLVVXHV
,QYHVWLJDWRU'RFXPHQWDWLRQ5HVSRQVLELOLWLHV
$OOLQGLYLGXDOVXEMHFWVSHFLILFVWXG\GDWDZLOODOVREHHQWHUHGLQWRD&)5
3DUWFRPSOLDQW('&V\VWHPRQDQH&5)LQDWLPHO\IDVKLRQ
$OOGDWDJHQHUDWHGIURPH[WHUQDOVRXUFHVHJODERUDWRU\DQGELRDQDO\WLFDOGDWDDQG
WUDQVPLWWHGWR&RYDQFHHOHFWURQLFDOO\ZLOOEHLQWHJUDWHGZLWKWKHVXEMHFW¶VH&5)GDWDLQ
DFFRUGDQFHZLWKWKH'DWD0DQDJHPHQW3ODQ
$QH&5)PXVWEHFRPSOHWHGIRUHDFKVXEMHFWDFFRUGLQJWRWKHH&5)FRPSOHWLRQ
LQVWUXFWLRQV7KHVSRQVRURU&52ZLOOUHYLHZWKHVXSSRUWLQJVRXUFHGRFXPHQWDWLRQDJDLQVW
WKHGDWDHQWHUHGLQWRWKHH&5)VWRYHULI\WKHDFFXUDF\RIWKHHOHFWURQLFGDWD7KHLQYHVWLJDWRU
ZLOOHQVXUHWKDWFRUUHFWLRQVDUHPDGHWRWKHH&5)VDQGWKDWGDWDTXHULHVDUHUHVROYHGLQD
WLPHO\IDVKLRQE\WKHVWXG\VWDII


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
7KHLQYHVWLJDWRUZLOOVLJQDQGGDWHWKHH&5)YLDWKH('&V\VWHP¶VHOHFWURQLFVLJQDWXUH
SURFHGXUH7KHVHVLJQDWXUHVZLOOLQGLFDWHWKDWWKHLQYHVWLJDWRUUHYLHZHGDQGDSSURYHGWKHGDWD
RQWKHH&5)GDWDTXHULHVDQGVLWHQRWLILFDWLRQV
3XEOLFDWLRQV
,IRQFRPSOHWLRQRIWKHVWXG\WKHGDWDZDUUDQWSXEOLFDWLRQWKHVSRQVRUUHWDLQVDOOULJKWVWR
SXEOLVKRUQRWSXEOLVKWKHUHVXOWV
6WXG\)LOHVDQG5HWHQWLRQRI5HFRUGV
7KHLQYHVWLJDWRUPXVWPDLQWDLQDGHTXDWHDQGDFFXUDWHUHFRUGVWRHQDEOHWKHFRQGXFWRIWKH
VWXG\WREHIXOO\GRFXPHQWHGDQGWKHVWXG\GDWDWREHVXEVHTXHQWO\YHULILHG
7KHVHGRFXPHQWVVKRXOGEHFODVVLILHGLQWRDWOHDVWWKHIROORZLQJFDWHJRULHV
LQYHVWLJDWRU¶VVWXG\ILOHDQGVXEMHFWFOLQLFDOVRXUFHGRFXPHQWV
7KHLQYHVWLJDWRU¶VVWXG\ILOHZLOOFRQWDLQWKHSURWRFRODPHQGPHQWVH&5)DQGTXHU\IRUPV
,5%DQGJRYHUQPHQWDODSSURYDOZLWKFRUUHVSRQGHQFH,&)GUXJUHFRUGVVWDIIFXUULFXOXP
YLWDHDQGDXWKRUL]DWLRQIRUPVDQGRWKHUDSSURSULDWHGRFXPHQWVDQGFRUUHVSRQGHQFH
6XEMHFWFOLQLFDOVRXUFHGRFXPHQWVXVXDOO\GHILQHGE\WKHSURMHFWLQDGYDQFHWRUHFRUGNH\
HIILFDF\VDIHW\SDUDPHWHUVLQGHSHQGHQWRIWKHH&5)VZRXOGLQFOXGHDOWKRXJKQRWEHOLPLWHG
WRWKHIROORZLQJVXEMHFWKRVSLWDOFOLQLFUHFRUGVSK\VLFLDQ¶VDQGQXUVH¶VQRWHVDSSRLQWPHQW
ERRNRULJLQDOODERUDWRU\UHSRUWV(&*HOHFWURHQFHSKDORJUDP;UD\SDWKRORJ\DQGVSHFLDO
DVVHVVPHQWUHSRUWVFRQVXOWDQWOHWWHUVVFUHHQLQJDQGHQUROOPHQWORJ
)ROORZLQJFORVXUHRIWKHVWXG\WKHLQYHVWLJDWRUPXVWPDLQWDLQDOOVWXG\UHFRUGVLQDVDIHDQG
VHFXUHORFDWLRQ7KHUHFRUGVPXVWEHPDLQWDLQHGWRDOORZHDV\DQGWLPHO\UHWULHYDOZKHQ
QHHGHGHJDXGLWRULQVSHFWLRQDQGZKHQHYHUIHDVLEOHWRDOORZDQ\VXEVHTXHQWUHYLHZRI
GDWDLQFRQMXQFWLRQZLWKDVVHVVPHQWRIWKHIDFLOLW\VXSSRUWLQJV\VWHPVDQGSHUVRQQHO
7KHVSRQVRUZLOOLQIRUPWKHLQYHVWLJDWRURIWKHWLPHSHULRGIRUUHWDLQLQJWKHVHUHFRUGVWR
FRPSO\ZLWKDOODSSOLFDEOHUHJXODWRU\UHTXLUHPHQWV7KHPLQLPXPUHWHQWLRQWLPHZLOOPHHW
WKHVWULFWHVWVWDQGDUGDSSOLFDEOHWRWKDWVWXG\FHQWHUIRUWKHVWXG\DVGLFWDWHGE\DQ\
LQVWLWXWLRQDOUHTXLUHPHQWVRUORFDOODZVRUUHJXODWLRQVRUWKHVSRQVRU¶VVWDQGDUGVSURFHGXUHV
RWKHUZLVHWKHUHWHQWLRQSHULRGZLOOGHIDXOWWR\HDUV
7KHLQYHVWLJDWRUPXVWQRWLI\WKHVSRQVRURIDQ\FKDQJHVLQWKHDUFKLYDODUUDQJHPHQWV
LQFOXGLQJEXWQRWOLPLWHGWRWKHIROORZLQJDUFKLYLQJDWDQRIIVLWHIDFLOLW\DQGWUDQVIHURI
RZQHUVKLSRIRUUHVSRQVLELOLW\IRUWKHUHFRUGVLQWKHHYHQWWKHLQYHVWLJDWRUOHDYHVWKHVWXG\
FHQWHU
,IWKHLQYHVWLJDWRUFDQQRWJXDUDQWHHWKLVDUFKLYLQJUHTXLUHPHQWDWWKHVWXG\VLWHIRUDQ\RUDOO
RIWKHGRFXPHQWVDUUDQJHPHQWVPXVWEHPDGHEHWZHHQWKHLQYHVWLJDWRUDQGVSRQVRUWRVWRUH
WKHVHLQVHFXUHFRQWDLQHUVRXWVLGHRIWKHVWXG\FHQWHUVRWKDWWKH\FDQEHUHWXUQHGWRWKH
LQYHVWLJDWRULQFDVHRIDUHJXODWRU\DXGLW:KHQVRXUFHGRFXPHQWVDUHUHTXLUHGIRUWKH
FRQWLQXHGFDUHRIWKHVXEMHFWDSSURSULDWHFRSLHVVKRXOGEHPDGHIRUVWRUDJHRXWVLGHRIWKH
VWXG\FHQWHU


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
%LRORJLFDOVDPSOHVDWWKHFRQFOXVLRQRIWKLVVWXG\PD\EHUHWDLQHGDVRXWOLQHGLQWKH
DJUHHPHQWZLWKWKH&52PDQDJLQJWKHELRORJLFDOVDPSOHVIRUWKHVKRUWHURIDSHULRGRIXS
WR\HDUVRUDVDOORZHGE\WKHVLWH¶V,5%
,QIRUPDWLRQ'LVFORVXUHDQG,QYHQWLRQV
$OOLQIRUPDWLRQSURYLGHGE\WKHVSRQVRUDQGDOOGDWDDQGLQIRUPDWLRQJHQHUDWHGE\WKHVWXG\
FHQWHUDVSDUWRIWKHVWXG\RWKHUWKDQDVXEMHFW¶VPHGLFDOUHFRUGVDUHWKHVROHSURSHUW\RIWKH
VSRQVRU
$OOULJKWVWLWOHDQGLQWHUHVWVLQDQ\LQYHQWLRQVNQRZKRZRURWKHULQWHOOHFWXDORULQGXVWULDO
SURSHUW\ULJKWVWKDWDUHFRQFHLYHGRUUHGXFHGWRSUDFWLFHE\WKHVWXG\FHQWHUSHUVRQQHOGXULQJ
WKHFRXUVHRIRUDVDUHVXOWRIWKHVWXG\DUHWKHVROHSURSHUW\RIWKHVSRQVRUDQGDUHKHUHE\
DVVLJQHGWRWKHVSRQVRU
,IDZULWWHQFRQWUDFWIRUWKHFRQGXFWRIWKHVWXG\WKDWLQFOXGHVRZQHUVKLSSURYLVLRQV
LQFRQVLVWHQWZLWKWKLVVWDWHPHQWLVH[HFXWHGEHWZHHQWKHVSRQVRUDQGWKHVWXG\FHQWHUWKDW
FRQWUDFW¶VRZQHUVKLSSURYLVLRQVVKDOODSSO\UDWKHUWKDQWKLVVWDWHPHQW


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
$SSHQGL[6FKHGXOHRI$VVHVVPHQWV


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
6FKHGXOHRI$VVHVVPHQWV
 6FUHHQLQJ
&KHFNLQ
7UHDWPHQW3HULRG
'LVFKDUJH
)ROORZXS9LVLW
RU(7D
6WXG\'D\
WR














GD\
3URFHGXUH
















,QIRUPHG&RQVHQW
;















5HYLHZ,QFOXVLRQ([FOXVLRQ&ULWHULD
;
;














'HPRJUDSKLFV
;















0HGLFDO+LVWRU\
;
;E














+HLJKW:HLJKWDQG%0,
;
;F













;F
'UXJ6FUHHQLQFOXGLQJFRWLQLQH
;
;














$OFRKRO7HVW

;














6HURORJ\
;















7XEHUFXORVLVWHVW
;















(VWLPDWHGJORPHUXODUILOWUDWLRQUDWH
;















6WXG\UHVLGHQF\
















&KHFNLQ

;














&KHFNRXW














;

1RQUHVLGHQWLDOYLVLW
;














;
6WXG\'UXJ$GPLQLVWUDWLRQ
















=DQXEUXWLQLE$GPLQLVWUDWLRQG


;









;



5LIDEXWLQ$GPLQLVWUDWLRQH




;
;
;
;
;
;
;
;
;



3KDUPDFRNLQHWLFV
















3.%ORRG6DPSOHVI


;
;








;
;


6DIHW\DVVHVVPHQWV
















3K\VLFDO([DPLQDWLRQ

;

;J











;
&OLQLFDO/DERUDWRU\(YDOXDWLRQVK
;
;

;
;









;
;
6LQJOH6DIHW\OHDG(&*L
;
;
;
;








;
;

;
9LWDO6LJQVM
;
;
;
;








;
;

;
3ULRUDQG&RQFRPLWDQW0HGLFDWLRQV
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
$(VDQG6$(VN
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;
;


3URWRFRO
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
3URWRFRO9HUVLRQ-XO\
3DJHRI
$EEUHYLDWLRQV$( DGYHUVHHYHQW%0, ERG\PDVVLQGH[(&* HOHFWURFDUGLRJUDP(7 HDUO\WHUPLQDWLRQ3. SKDUPDFRNLQHWLF6$( VHULRXVDGYHUVHHYHQW
1RWH:KHUHDFWLYLWLHVDWDJLYHQWLPHSRLQWFRLQFLGHFRQVLGHUDWLRQPXVWEHJLYHQWRHQVXUHWKDWWKHIROORZLQJRUGHURIDFWLYLWLHVLVPDLQWDLQHG(&*VYLWDOVLJQVEORRG
GUDZV
D6XEMHFWVZKRZLWKGUDZIURPWKHVWXG\SULRUWR'D\VKRXOGXQGHUJRDOOIROORZXSDVVHVVPHQWVDW(7
E,QWHULPPHGLFDOKLVWRU\XSGDWHRQO\
F:HLJKWRQO\
G=DQXEUXWLQLELVWREHDGPLQLVWHUHGGXULQJWKHPRUQLQJRI'D\DQGRQ'D\DWWKHVDPHWLPHDVWKHULIDEXWLQGRVH
H5LIDEXWLQLVWREHDGPLQLVWHUHGRQFHGDLO\RQ'D\VWKURXJK2Q'D\]DQXEUXWLQLEZLOOEHDGPLQLVWHUHGDWWKHVDPHWLPHDVWKHGRVHRIULIDEXWLQ
I%ORRGVDPSOHVIRUDQDO\VLVRISODVPD]DQXEUXWLQLEZLOOEHFROOHFWHGSUHGRVHDQGDQGKRXUVSRVWGRVH7KHDOORZHGVDPSOLQJZLQGRZIRU
3.EORRGVDPSOHVZLOOEHWKHIROORZLQJZLWKLQPLQXWHVSULRUWRGRVLQJIRUWKHSUHGRVHVDPSOHWLPHSRLQWPLQXWHVIRUVDPSOLQJWLPHSRLQWVKRXUVPLQXWHV
IRUVDPSOLQJWLPHSRLQWDWDQGKRXUV
J6\PSWRPGLUHFWHGSK\VLFDOH[DPLQDWLRQ
K&ROOHFWLRQRIEORRGIRUFOLQLFDOFKHPLVWU\DQGKHPDWRORJ\SDUDPHWHUVIDVWHGDWOHDVWKRXUVDQGXULQHFROOHFWLRQIRUXULQDO\VLVZLOOEHSHUIRUPHGDWVFUHHQLQJFKHFNLQ
'D\VDQGDWGLVFKDUJHDQGDWIROORZXSRU(7
L6LQJOHVDIHW\OHDG(&*VZLOOEHFROOHFWHGDWVFUHHQLQJFKHFNLQRQ'D\VDQGDWSUHGRVHDQGDQGKRXUVSRVWGRVHDQGDWIROORZXSRU(7$OO(&*V
VKRXOGEHFROOHFWHGDIWHUWKHVXEMHFWKDVUHVWHGLQWKHVXSLQHSRVLWLRQIRUDWOHDVWPLQXWHVDQGZLOOEHREWDLQHGSULRUWRYLWDOVLJQVDQGDVFORVHDVSRVVLEOHWRWKHVFKHGXOHG
EORRGGUDZV
M9LWDOVLJQPHDVXUHPHQWVVXSLQHEORRGSUHVVXUHVXSLQHSXOVHUDWHUHVSLUDWRU\UDWHDQGRUDOERG\WHPSHUDWXUHZLOOEHREWDLQHGDWVFUHHQLQJDQGFKHFNLQRQ'D\VDQG
DWSUHGRVHDQGDQGKRXUVSRVWGRVHDQGDWIROORZXSRU(79LWDOVLJQPHDVXUHPHQWVVKRXOGEHFDUULHGRXWDIWHU(&*VDQGSULRUWRDQGDVFORVHDVSRVVLEOHWR
KDYLQJEORRGGUDZQ%ORRGSUHVVXUHDQGSXOVHUDWHZLOOEHPHDVXUHGXVLQJWKHVDPHDUPIRUHDFKUHDGLQJDIWHUWKHVXEMHFWKDVEHHQVXSLQHIRUDWOHDVWPLQXWHV
N$OOQRQVHULRXV$(VZKHWKHUUHSRUWHGE\WKHVXEMHFWYROXQWDULO\RUXSRQTXHVWLRQLQJRUQRWHGRQSK\VLFDOH[DPLQDWLRQZLOOEHUHFRUGHGIURPWKHWLPHRIVWXG\GUXJ
DGPLQLVWUDWLRQXQWLOVWXG\FRPSOHWLRQ$OO6$(VZLOOEHUHFRUGHGIURPWKHWLPHWKHVXEMHFWVLJQVWKHLQIRUPHGFRQVHQWIRUPXQWLOVWXG\FRPSOHWLRQ

SAP_001.pdf: 
TITLE PAGE 
Statistical Analysis Plan 
A Phase 1, Open-label, Fixed-sequence Study to Investigate the Effect of 
the Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of 
Zanubrutinib in Healthy Male Subjects 
6$36WDWXV)LQDO
6$39HUVLRQ
6$3'DWH2&7
,QYHVWLJDWLRQDO3URGXFW=DQXEUXWLQLE%*%
3URWRFRO5HIHUHQFH%*%
&RYDQFH6WXG\
6SRQVRU
%HL*HQH/WG
FR%HL*HQH86$,QF
&DPSXV'ULYH6XLWH
6DQ0DWHR&DOLIRUQLD
86$
6WXG\6LWH
&RYDQFH&OLQLFDO5HVHDUFK8QLW,QF
0DVRQ$YH6XLWH
'D\WRQD%HDFK)ORULGD
86$
3ULQFLSDO,QYHVWLJDWRU

,QIRUPDWLRQGHVFULEHGKHUHLQLVFRQILGHQWLDODQGPD\EHGLVFORVHGRQO\ZLWKWKHH[SUHVV
ZULWWHQSHUPLVVLRQRIWKHVSRQVRU
Page 2 of 20
1&7


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
TABLE OF CONTENTS 
7,7/(3$*( 
7$%/(2)&217(176 
/,672)$%%5(9,$7,216 
,1752'8&7,21 
678'<2%-(&7,9(6 
678'<(1'32,176 
3ULPDU\(QGSRLQWV 
6HFRQGDU\(QGSRLQWV 
678'<'(6,*1 
6$03/(6,=(-867,),&$7,21 
678'<75($70(176 
'(),1,7,2162)3238/$7,216 
$OO6XEMHFWV3RSXODWLRQ 
6DIHW\3RSXODWLRQ 
3KDUPDFRNLQHWLF3RSXODWLRQ 
67$7,67,&$/0(7+2'2/2*< 
*HQHUDO 
&DOFXODWLRQRIWKH6XPPDU\6WDWLVWLFV 
5HSHDWDQG8QVFKHGXOHG5HDGLQJV 
'HILQLWLRQVRI%DVHOLQHDQG&KDQJHIURP%DVHOLQH 
6XEMHFW'LVSRVLWLRQ3RSXODWLRQ$VVLJQPHQWDQG3URWRFRO'HYLDWLRQV 
'HPRJUDSKLFV 
3ULRUDQG&RQFRPLWDQW0HGLFDWLRQ 
3KDUPDFRNLQHWLF$VVHVVPHQWV 
3KDUPDFRNLQHWLF$QDO\VLV 
3UHVHQWDWLRQRI3KDUPDFRNLQHWLF'DWD 
3KDUPDFRNLQHWLF6WDWLVWLFDO0HWKRGRORJ\ 
6DIHW\DQG7ROHUDELOLW\$VVHVVPHQWV 
$GYHUVH(YHQWV 
&OLQLFDO/DERUDWRU\3DUDPHWHUV 
9LWDO6LJQV3DUDPHWHUV 
OHDG(OHFWURFDUGLRJUDP3DUDPHWHUV 
Page 3 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
2WKHU$VVHVVPHQWV 
6DIHW\DQG7ROHUDELOLW\6WDWLVWLFDO0HWKRGRORJ\ 
,17(5,0$1$/<6(6 
6,*1,),&$17&+$1*(6)5207+(35272&2/63(&,),('$1$/<6(6 
5()(5(1&(6 
$33(1',&(6 
Page 4 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
LIST OF ABBREVIATIONS 
$EEUHYLDWLRQVSHUWDLQWRWKHVWDWLVWLFDODQDO\VLVSODQ6$3RQO\QRWWKHWDEOHVILJXUHVDQG
OLVWLQJV>7)/V@
$'D0
DQDO\VLVGDWDPRGHO
$(
DGYHUVHHYHQW
$8&
DUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYH
$8&
DUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHIURPWLPH]HURWRLQILQLW\
$8&W
DUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHIURPWLPH]HURWRWKHWLPHRI
WKHODVWTXDQWLILDEOHFRQFHQWUDWLRQ
%/4
EHORZWKHOLPLWRITXDQWLILFDWLRQ
&',6&
&OLQLFDO'DWD,QWHUFKDQJH6WDQGDUGV&RQVRUWLXP
&,
FRQILGHQFHLQWHUYDO
&/)
DSSDUHQWRUDOFOHDUDQFH
&PD[
PD[LPXPREVHUYHGFRQFHQWUDWLRQ
&65
FOLQLFDOVWXG\UHSRUW
&7&$(
&RPPRQ7HUPLQRORJ\&ULWHULDIRU$GYHUVH(YHQWV
&9
FRHIILFLHQWRIYDULDWLRQ
(&*
HOHFWURFDUGLRJUDP
*/60
JHRPHWULFOHDVWVTXDUHVPHDQ
,&+
,QWHUQDWLRQDO&RXQFLOIRU&RQIHUHQFHRQ+DUPRQLVDWLRQRI7HFKQLFDO
5HTXLUHPHQWVIRU5HJLVWUDWLRQRI3KDUPDFHXWLFDOVIRU+XPDQ8VH
OQ
QDWXUDOORJ
/60
OHDVWVTXDUHVPHDQ
0HG'5$
0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV
3.
SKDUPDFRNLQHWLFV
6$3
VWDWLVWLFDODQDO\VLVSODQ
6'
VWDQGDUGGHYLDWLRQ
W
DSSDUHQWWHUPLQDOHOLPLQDWLRQKDOIOLIH
7($(
WUHDWPHQWHPHUJHQWDGYHUVHHYHQW
7)/
WDEOHILJXUHDQGOLVWLQJ
7PD[
WLPHRIWKHPD[LPXPREVHUYHGFRQFHQWUDWLRQ
7ODVW
WLPHRIWKHODVWTXDQWLILDEOHFRQFHQWUDWLRQ
9])
DSSDUHQWYROXPHRIGLVWULEXWLRQ
:+2'UXJ
:RUOG+HDOWK2UJDQL]DWLRQ'UXJ'LFWLRQDU\
$8&H[WUDS
SHUFHQWDJHRI$8&GXHWRH[WUDSRODWLRQIURPWKHODVWTXDQWLILDEOH
FRQFHQWUDWLRQWRLQILQLW\


Page 5 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
1. INTRODUCTION 
7KLV6$3KDVEHHQGHYHORSHGDIWHUUHYLHZRIWKHFOLQLFDOVWXG\SURWRFRO)LQDO9HUVLRQ
GDWHG-XO\DQGHOHFWURQLFFDVHUHSRUWIRUP
7KLV6$3GHVFULEHVWKHSODQQHGDQDO\VLVRIWKHSKDUPDFRNLQHWLF3.DQGVDIHW\DQG
WROHUDELOLW\GDWDIURPWKLVVWXG\$GHWDLOHGGHVFULSWLRQRIWKHSODQQHG7)/VWREHSUHVHQWHG
LQWKHFOLQLFDOVWXG\UHSRUW&65LVSURYLGHGLQWKHDFFRPSDQ\LQJ7)/VKHOOVGRFXPHQW
,QJHQHUDOWKHDQDO\VHVDUHEDVHGRQLQIRUPDWLRQIURPWKHSURWRFROXQOHVVWKH\KDYHEHHQ
PRGLILHGE\DJUHHPHQWZLWK%HL*HQH/WG$OLPLWHGDPRXQWRILQIRUPDWLRQDERXWWKLVVWXG\
HJREMHFWLYHVVWXG\GHVLJQLVJLYHQWRKHOSWKHUHDGHU¶VLQWHUSUHWDWLRQ7KLV6$3PXVWEH
ILQDOL]HGSULRUWRWKHORFNRIWKHFOLQLFDOGDWDEDVHIRUWKLVVWXG\:KHQWKH6$3DQG7)/
VKHOOVDUHDSSURYHGWKH\ZLOOVHUYHDVWKHWHPSODWHIRUWKLVVWXG\¶V&65
7KLV6$3VXSHUVHGHVDQ\VWDWLVWLFDOFRQVLGHUDWLRQVLGHQWLILHGLQWKHSURWRFROZKHUH
FRQVLGHUDWLRQVDUHVXEVWDQWLDOO\GLIIHUHQWWKH\ZLOOEHVRLGHQWLILHG,IDGGLWLRQDODQDO\VHVDUH
UHTXLUHGWRVXSSOHPHQWWKHSODQQHGDQDO\VHVGHVFULEHGLQWKLV6$3WKH\PD\EHSHUIRUPHG
DQGZLOOEHLGHQWLILHGDFFRUGLQJO\LQWKH&65$Q\VXEVWDQWLDOGHYLDWLRQVIURPWKLV6$3ZLOO
EHDJUHHGZLWK%HL*HQH/WGDQGLGHQWLILHGLQWKH&65
7KLV6$3LVZULWWHQZLWKFRQVLGHUDWLRQRIWKHUHFRPPHQGDWLRQVRXWOLQHGLQWKH,QWHUQDWLRQDO
&RQIHUHQFHRQ+DUPRQLVDWLRQ,&+(JXLGHOLQHStatistical Principles for Clinical Trials
DQG,&+(JXLGHOLQHStructure and Content of Clinical Study Reports
7KHGRFXPHQWKLVWRU\LVSUHVHQWHGLQ$SSHQGL[
2. STUDY OBJECTIVES  
7KHSULPDU\REMHFWLYHRIWKHVWXG\LV
x WRGHWHUPLQHWKHHIIHFWRIWKHPRGHUDWH&<3$LQGXFHUULIDEXWLQRQWKH3.RI
]DQXEUXWLQLELQKHDOWK\PDOHVXEMHFWV
7KHVHFRQGDU\REMHFWLYHRIWKHVWXG\LV
x WRHYDOXDWHWKHVDIHW\DQGWROHUDELOLW\RI]DQXEUXWLQLEZKHQFRDGPLQLVWHUHGZLWK
ULIDEXWLQLQKHDOWK\PDOHVXEMHFWV
3. STUDY ENDPOINTS  
3.1. Primary Endpoints 
7KH3.RXWFRPHHQGSRLQWVRI]DQXEUXWLQLEGHULYHGIURPWKHSODVPDFRQFHQWUDWLRQWLPH
SURILOHVIROORZLQJRUDODGPLQLVWUDWLRQRI]DQXEUXWLQLERQ'D\VDQGDUHDVIROORZV
x DUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYH$8&IURPWLPH]HURWRWKHWLPHRIWKHODVW
TXDQWLILDEOHFRQFHQWUDWLRQ$8&W
x $8&IURPWLPH]HURWRLQILQLW\$8&
Page 6 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
x PD[LPXPREVHUYHGFRQFHQWUDWLRQ&PD[
x WLPHRIWKHPD[LPXPREVHUYHGFRQFHQWUDWLRQ7PD[
x DSSDUHQWWHUPLQDOHOLPLQDWLRQKDOIOLIHW
x DSSDUHQWRUDOFOHDUDQFH&/)
x DSSDUHQWYROXPHRIGLVWULEXWLRQ9])
2WKHU3.SDUDPHWHUVPD\DOVREHUHSRUWHG
3.2. Secondary Endpoints 
7KHVDIHW\RXWFRPHPHDVXUHVIRUWKLVVWXG\DUHDVIROORZV
x LQFLGHQFHDQGVHYHULW\RIDGYHUVHHYHQWV$(V
x LQFLGHQFHRIODERUDWRU\DEQRUPDOLWLHVEDVHGRQKHPDWRORJ\FOLQLFDOFKHPLVWU\DQG
XULQDO\VLVWHVWUHVXOWV
x YLWDOVLJQPHDVXUHPHQWV
x OHDGHOHFWURFDUGLRJUDP(&*SDUDPHWHUV
x SK\VLFDOH[DPLQDWLRQV
4. STUDY DESIGN  
7KLVLVDQRSHQODEHOIL[HGVHTXHQFHVWXG\LQKHDOWK\PDOHVXEMHFWVWRLQYHVWLJDWHWKHHIIHFW
RI&<3$LQGXFWLRQE\VWHDG\VWDWHULIDEXWLQRQWKHVLQJOHGRVH3.RI]DQXEUXWLQLE
$OOVXEMHFWVZLOOUHFHLYHWKHIROORZLQJWUHDWPHQWV
x 'D\VLQJOHRUDOGRVHRIPJ]DQXEUXWLQLEDIWHURYHUQLJKWIDVWRIWRKRXUV
x 'D\VWRRUDOGRVHRIPJULIDEXWLQ4'ZLWKIRRGVWDQGDUGPHDO
x 'D\VLQJOHRUDOGRVHRIPJ]DQXEUXWLQLEDQG4'GRVHRIPJULIDEXWLQ
DIWHURYHUQLJKWIDVWRIWRKRXUV
5. SAMPLE SIZE JUSTIFICATION  
$SSUR[LPDWHO\VXEMHFWVZLOOEHHQUROOHGWRHQVXUHWKDWVXEMHFWVFRPSOHWHWKHVWXG\
7KHVDPSOHVL]HFKRVHQIRUWKLVVWXG\ZDVEDVHGRQSUHFHGHQWVHWE\RWKHU3.VWXGLHVRI
VLPLODUQDWXUHDQGZDVQRWEDVHGRQSRZHUFDOFXODWLRQV
6. STUDY TREATMENTS  
$OOVXPPDULHVZLOOEHSURYLGHGIRUWKHWRWDOQXPEHURIWUHDWHGVXEMHFWV)RUWKHVXPPDULHV
RI$(VVXPPDULHVZLOODOVREHSURYLGHGDFFRUGLQJWRWKHVWXG\GD\RIRQVHWRIWKH$(7KH
VWXG\WUHDWPHQWVHTXHQFHQDPHWREHXVHGLQWKH$(VXPPDULHVLVSUHVHQWHGLQ7DEOH
Page 7 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
Table 1: 
Presentation of Study Treatment Sequence for AE summaries 
Study Treatment Sequence 
Includes AEs with Onset on Study Day: 
PJ=DQXEUXWLQLERQ'D\

PJ5LIDEXWLQRQ'D\VWR

PJ=DQXEUXWLQLEPJ5LIDEXWLQRQ'D\

VWXG\FRPSOHWLRQ
7KHVWXG\GD\VGHVFULEHGDERYHDUHWKHSODQQHGVWXG\GD\V7KH$(VXPPDULHVDFFRUGLQJWR
WUHDWPHQWVHTXHQFHZLOOUHIOHFWWKHDFWXDOVWXG\GD\VRQZKLFKWUHDWPHQWVZHUHUHFHLYHG
7KHVWXG\WUHDWPHQWQDPHVDQGRUGHULQJWREHXVHGLQWKH7)/VDUHSUHVHQWHGLQ7DEOH
Table 2: 
Presentation of Study Treatments in TFLs  
Study Treatment 
Order in TFLs 
PJ=DQXEUXWLQLE

PJ5LIDEXWLQ

PJ=DQXEUXWLQLEPJ5LIDEXWLQ

7. DEFINITIONS OF POPULATIONS  
7.1. All Subjects Population  
7KHDOOVXEMHFWVSRSXODWLRQZLOOLQFOXGHDOOVXEMHFWVZKRVLJQHGWKHLQIRUPHGFRQVHQWIRUP
DQGKDGDQ\VWXG\DVVHVVPHQWUHFRUGHGLQWKHGDWDEDVHSHUWKHSURWRFRO
7.2. Safety Population  
7KHVDIHW\SRSXODWLRQZLOOLQFOXGHDOOVXEMHFWVZKRUHFHLYHGDWOHDVWGRVHRI]DQXEUXWLQLE
DQGRUULIDEXWLQ
7.3. Pharmacokinetic Population  
7KH3.SRSXODWLRQZLOOLQFOXGHDOOVXEMHFWVZKRUHFHLYHGDWOHDVWGRVHRI]DQXEUXWLQLEDQG
KDYHHYDOXDEOH3.GDWDDWOHDVW3.SDUDPHWHUFDQEHFDOFXODWHG$VXEMHFWPD\EH
H[FOXGHGIURPWKH3.VXPPDU\VWDWLVWLFVDQGVWDWLVWLFDODQDO\VLVLIWKHVXEMHFWKDVDQ$(RI
YRPLWLQJWKDWRFFXUVDWRUEHIRUHîPHGLDQ7PD[
8. STATISTICAL METHODOLOGY  
8.1. General  
/LVWLQJVZLOOEHSURYLGHGIRUDOOGDWDFDSWXUHGLQWKHGDWDEDVH/LVWLQJVZLOOLQFOXGHDOO
VXEMHFWVDVVLJQHGWRWKHDOOVXEMHFWVSRSXODWLRQDQGLQFOXGHGDWDXSWRWKHSRLQWRIVWXG\
FRPSOHWLRQRUGLVFRQWLQXDWLRQ6XEMHFWVDUHJHQHUDOO\FRQVLGHUHGWRKDYHFRPSOHWHGWKHVWXG\
LIWKH\FRPSOHWHGDOOSURWRFROVSHFLILHGSURFHGXUHVDQGDVVHVVPHQWVIRUWKHIROORZXSYLVLW
$Q\VXEMHFWZKRGLVFRQWLQXHGWKHVWXG\ZLOOEHLGHQWLILHGDFFRUGLQJO\LQWKHOLVWLQJV
Page 8 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
6XPPDULHVDQGVWDWLVWLFDODQDO\VHVZLOOLQFOXGHWKHVXEMHFWVDVVLJQHGWRWKHUHOHYDQW
SRSXODWLRQEDVHGRQGDWDW\SH
'DWDDQDO\VLVZLOOEHSHUIRUPHGXVLQJWKH6$6VWDWLVWLFDOVRIWZDUHSDFNDJH9HUVLRQRU
KLJKHULIXSYHUVLRQHGGXULQJWKHVWXG\
$QDO\VLV'DWD0RGHO$'D0GDWDVHWVZLOOEHSUHSDUHGXVLQJ&OLQLFDO'DWD,QWHUFKDQJH
6WDQGDUGV&RQVRUWLXP&',6&$'D09HUVLRQRUKLJKHULIXSYHUVLRQHGGXULQJWKH
VWXG\DQG&',6&$'D0,PSOHPHQWDWLRQ*XLGH9HUVLRQRUKLJKHULIXSYHUVLRQHG
GXULQJWKHVWXG\3LQQDFOH&RPPXQLW\9DOLGDWRU9HUVLRQRUKLJKHULIXSYHUVLRQHG
GXULQJWKHVWXG\ZLOOEHXWLOL]HGWRHQVXUHFRPSOLDQFHZLWK&',6&VWDQGDUGV
:KHUHUHIHUHQFHLVPDGHWRµDOOFDOFXODWLRQV¶WKLVLQFOXGHVEXWLVQRWOLPLWHGWRVXPPDU\
VWDWLVWLFVDQGVWDWLVWLFDODQDO\VHV
8.1.1. Calculation of the Summary Statistics  
)RUFRQWLQXRXVGDWDWKHIROORZLQJUXOHVZLOOEHDSSOLHG
Ɣ 0LVVLQJYDOXHVZLOOQRWEHLPSXWHGXQOHVVVSHFLILFDOO\VWDWHGRWKHUZLVH
Ɣ 8QURXQGHGGDWDZLOOEHXVHGLQWKHFDOFXODWLRQRIVXPPDU\VWDWLVWLFV
Ɣ ,IWKHQXPEHURIVXEMHFWVZLWKYDOLGREVHUYDWLRQVQVXPPDU\VWDWLVWLFVZLOOQRWEH
FDOFXODWHGZLWKWKHH[FHSWLRQRIQPLQLPXPDQGPD[LPXP
Ɣ $V(DUO\7HUPLQDWLRQGDWDLVQRWDVVRFLDWHGZLWKDQ\VFKHGXOHGWLPHSRLQWLWZLOOEH
H[FOXGHGIURPDOOFDOFXODWLRQVRIVXPPDU\VWDWLVWLFV
)RUFDWHJRULFDOGDWDWKHIROORZLQJUXOHVZLOOEHDSSOLHG
Ɣ ,IWKHFDWHJRULHVRIDSDUDPHWHUDUHRUGHUHGHJ$(VHYHULW\DOOFDWHJRULHVEHWZHHQWKH
SRVVLEOHPLQLPXPDQGPD[LPXPFDWHJRULHVZLOOEHLQFOXGHGHYHQLIQ IRUDJLYHQ
FDWHJRU\,IWKHFDWHJRULHVDUHQRWRUGHUHGHJUDFHRQO\WKRVHFDWHJRULHVIRUZKLFK
WKHUHLVDWOHDVWVXEMHFWUHSUHVHQWHGZLOOEHLQFOXGHG
Ɣ 0LVVLQJYDOXHVZLOOQRWEHLPSXWHGZLWKWKHH[FHSWLRQRI$(VZKHUHWKHµZRUVWFDVH¶
DSSURDFKZLOOEHWDNHQVHH6HFWLRQRUXQOHVVVSHFLILFDOO\VWDWHGRWKHUZLVH$
µPLVVLQJ¶FDWHJRU\ZLOOEHLQFOXGHGIRUDQ\SDUDPHWHUIRUZKLFKLQIRUPDWLRQLVPLVVLQJ
7KLVZLOOHQVXUHWKDWWKHSRSXODWLRQVL]HWRWDOVDUHFRQVLVWHQWDFURVVGLIIHUHQW
SDUDPHWHUV
8.1.2. Repeat and Unscheduled Readings  
)RUYLWDOVLJQVDQG(&*GDWDRQO\DQ\SUHGRVHYDOXHUHFRUGHGLQDGGLWLRQWRWKHRULJLQDO
YDOXHRUDSRVWGRVHYDOXHUHFRUGHGZLWKLQPLQXWHVRIWKHRULJLQDOYDOXHZLOOEHGHILQHGDV
DUHSHDWYDOXH$Q\YDOXHUHFRUGHGLQDGGLWLRQWRWKHRULJLQDOYDOXHDQGUHSHDWYDOXHZLOOEH
GHILQHGDVDQXQVFKHGXOHGYDOXH
7KHRULJLQDOYDOXHZLOOEHUHSODFHGE\WKHODVWDVVRFLDWHGUHSHDWYDOXHLQDOOFDOFXODWLRQV
Page 9 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
$VXQVFKHGXOHGYDOXHVDUHQRWDVVRFLDWHGZLWKDQ\VFKHGXOHGWLPHSRLQWWKH\ZLOOEH
H[FOXGHGIURPDOOFDOFXODWLRQV
8.1.3. Definitions of Baseline and Change from Baseline 
)RUODERUDWRU\GDWDYLWDOVLJQVDQG(&*GDWDWKHEDVHOLQHZLOOEHGHILQHGDVWKHODVWQRQ
PLVVLQJYDOXHUHFRUGHGSULRUWRWKHILUVWGRVHRI]DQXEUXWLQLE,IWKHGDWHWLPHRIWKHYDOXHLV
LQFRPSOHWHRUPLVVLQJLWZLOOEHH[FOXGHGIURPWKHEDVHOLQHFDOFXODWLRQXQOHVVWKH
LQFRPSOHWHGDWHWLPHRUQRPLQDOWLPHSRLQWLQGLFDWHVWKHYDOXHZDVUHFRUGHGSULRUWRWKHILUVW
GRVH
,QGLYLGXDOFKDQJHVIURPEDVHOLQHZLOOEHFDOFXODWHGE\VXEWUDFWLQJWKHLQGLYLGXDOVXEMHFW¶V
EDVHOLQHYDOXHIURPWKHYDOXHDWWKHWLPHSRLQW7KHPHDQFKDQJHIURPEDVHOLQHZLOOEH
GHILQHGDVWKHPHDQRIWKHLQGLYLGXDOFKDQJHVIURPEDVHOLQHIRUDOOVXEMHFWV
6HH6HFWLRQIRUPRUHGHWDLORQKDQGOLQJUHSHDWDQGXQVFKHGXOHGUHDGLQJVLQWKH
FDOFXODWLRQV
)RUODERUDWRU\GDWDYLWDOVLJQVDQG(&*GDWDDEDVHOLQHYDOXHLVGHILQHGDVWKHODVWQRQ
PLVVLQJYDOXHFROOHFWHGEHIRUHWKHWLPHRIILUVWGRVHRI]DQXEUXWLQLE
8.2. Subject Disposition, Population Assignment, and Protocol Deviations 
6XEMHFWGLVSRVLWLRQDQGSRSXODWLRQDVVLJQPHQWZLOOEHOLVWHG
$VXPPDU\WDEOHZLOOEHSURYLGHGEDVHGRQWKHDOOVXEMHFWVSRSXODWLRQ
$Q\SURWRFROGHYLDWLRQVZLOOEHFRQVLGHUHGSULRUWRGDWDEDVHORFNIRUWKHLULPSRUWDQFHDQG
WDNHQLQWRFRQVLGHUDWLRQZKHQDVVLJQLQJVXEMHFWVWRSRSXODWLRQV$OLVWLQJRISURWRFRO
GHYLDWLRQVZLOOEHSURYLGHG,PSRUWDQWSURWRFROGHYLDWLRQVZLOOEHQRWHGLQWKHOLVWLQJ
8.3. Demographics 
'HPRJUDSKLFVLQFOXGLQJDJHVH[UDFHHWKQLFLW\KHLJKWERG\ZHLJKWDQGERG\PDVVLQGH[
ZLOOEHOLVWHG
$VXPPDU\WDEOHE\ZLOOEHSURYLGHGEDVHGRQWKHVDIHW\SRSXODWLRQ
8.4. Prior and Concomitant Medication  
3ULRUPHGLFDWLRQZLOOEHGHILQHGDVPHGLFDWLRQWKDWVWDUWVSULRUWRWKHILUVWGRVH&RQFRPLWDQW
PHGLFDWLRQZLOOEHGHILQHGDVPHGLFDWLRQWKDWVWDUWVGXULQJRUDIWHUWKHILUVWGRVHRUVWDUWVEXW
GRHVQRWHQGSULRUWRWKHILUVWGRVH0HGLFDWLRQVWKDWVWDUWSULRUWRWKHILUVWGRVHEXWGRQRW
HQGSULRUWRWKHILUVWGRVHZLOOEHFODVVLILHGDVERWKSULRUDQGFRQFRPLWDQWPHGLFDWLRQV
3ULRUDQGFRQFRPLWDQWPHGLFDWLRQVZLOOEHFRGHGXVLQJWKH:RUOG+HDOWK2UJDQL]DWLRQ'UXJ
'LFWLRQDU\:+2'UXJ*OREDO)RUPDW%9HUVLRQ0DUFKRUODWHULIXSYHUVLRQHG
GXULQJWKHVWXG\3ULRUDQGFRQFRPLWDQWPHGLFDWLRQVZLOOEHOLVWHG
Page 10 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
8.5. Pharmacokinetic Assessments 
8.5.1. Pharmacokinetic Analysis  
7KHIROORZLQJ3.SDUDPHWHUVZLOOEHGHWHUPLQHGZKHUHSRVVLEOHIURPWKHSODVPD
FRQFHQWUDWLRQVRI]DQXEUXWLQLEXVLQJQRQFRPSDUWPHQWDOPHWKRGVLQYDOLGDWHGVRIWZDUH
SURJUDP3KRHQL[:LQ1RQOLQ&HUWDUD9HUVLRQRUKLJKHU
Parameter 
Unitsa 
Definition 
$8&W
KQJP/
DUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHIURPWLPHWRWKHWLPHRI
WKHODVWTXDQWLILDEOHFRQFHQWUDWLRQ7ODVWE
$8&
KQJP/
DUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHIURPWLPHH[WUDSRODWHG
WRLQILQLW\F
$8&H[WUDS

SHUFHQWDJHRI$8&GXHWRH[WUDSRODWLRQIURPWKHODVWTXDQWLILDEOH
FRQFHQWUDWLRQWRLQILQLW\
&PD[
QJP/
PD[LPXPREVHUYHGFRQFHQWUDWLRQ
7PD[
K
WLPHRIWKHPD[LPXPREVHUYHGFRQFHQWUDWLRQ
7ODVW
K
WLPHRIWKHODVWTXDQWLILDEOHFRQFHQWUDWLRQ
W
K
DSSDUHQWWHUPLQDOHOLPLQDWLRQKDOIOLIH
&/)
/K
DSSDUHQWRUDOFOHDUDQFH
9])
/
DSSDUHQWYROXPHRIGLVWULEXWLRQ
D8QLWVDUHEDVHGRQFRQFHQWUDWLRQXQLWVSURYLGHGE\WKHELRDQDO\WLFDOODERUSUHIHUUHGXQLWVIRUSUHVHQWDWLRQRI3.
SDUDPHWHUVDQGGRVHXQLWVXVHGLQWKHVWXG\
E$UHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYHZLOOEHFDOFXODWHGXVLQJWKHOLQHDUWUDSH]RLGDOUXOHIRULQFUHDVLQJFRQFHQWUDWLRQV
DQGWKHORJDULWKPLFUXOHIRUGHFUHDVLQJFRQFHQWUDWLRQVOLQHDUXSORJGRZQUXOH
F%DVHGRQWKHODVWREVHUYHGTXDQWLILDEOHFRQFHQWUDWLRQ
$GGLWLRQDO3.SDUDPHWHUVPD\EHGHWHUPLQHGZKHUHDSSURSULDWH
3KDUPDFRNLQHWLFDQDO\VLVZLOOEHFDUULHGRXWZKHUHSRVVLEOHXVLQJDFWXDOEORRGVDPSOLQJ
WLPHVSRVWGRVH,IDQDFWXDOWLPHLVPLVVLQJWKHVDPSOHFRQFHQWUDWLRQUHVXOWZLOOEHWUHDWHGDV
PLVVLQJXQOHVVWKHUHLVVFLHQWLILFMXVWLILFDWLRQWRLQFOXGHWKHUHVXOWXVLQJWKHQRPLQDOWLPH
7KHSDUDPHWHUV&PD[7PD[DQG7ODVWZLOOEHREWDLQHGGLUHFWO\IURPWKHFRQFHQWUDWLRQWLPH
SURILOHV,I&PD[RFFXUVDWPRUHWKDQWLPHSRLQW7PD[ZLOOEHDVVLJQHGWRWKHILUVWRFFXUUHQFH
RI&PD[
8.5.1.1. Criteria for the Calculation of Apparent Terminal Elimination Rate Constant 
and Half-life 
7KHVWDUWRIWKHWHUPLQDOHOLPLQDWLRQSKDVHIRUHDFKVXEMHFWZLOOEHGHILQHGE\YLVXDO
LQVSHFWLRQDQGJHQHUDOO\ZLOOEHWKHILUVWSRLQWDWZKLFKWKHUHLVQRV\VWHPDWLFGHYLDWLRQIURP
WKHORJOLQHDUGHFOLQHLQFRQFHQWUDWLRQV
7KHDSSDUHQWWHUPLQDOHOLPLQDWLRQUDWHFRQVWDQWȜ]ZLOORQO\EHFDOFXODWHGZKHQDUHOLDEOH
HVWLPDWHFDQEHREWDLQHGXVLQJDWOHDVWGDWDSRLQWVSUHIHUDEO\QRWLQFOXGLQJ&PD[DQGWKH
DGMXVWHGFRHIILFLHQWIRUGHWHUPLQDWLRQRIH[SRQHQWLDOILW5DGMRIWKHUHJUHVVLRQOLQHLV

Page 11 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
3DUDPHWHUVUHTXLULQJȜ]IRUWKHLUFDOFXODWLRQHJ$8&W&/)DQG9])ZLOORQO\EH
FDOFXODWHGLIWKH5DGMYDOXHRIWKHUHJUHVVLRQOLQHLV
7KHIROORZLQJUHJUHVVLRQUHODWHGGLDJQRVWLF3.SDUDPHWHUVZLOOEHGHWHUPLQHGZKHQ
SRVVLEOH
Parameter 
Units 
Definition 
Ȝ]
K
DSSDUHQWWHUPLQDOHOLPLQDWLRQUDWHFRQVWDQW
Ȝ]8SSHU
K
HQGRIH[SRQHQWLDOILW
Ȝ]/RZHU
K
VWDUWRIH[SRQHQWLDOILW
Ȝ]1
1$
QXPEHURIGDWDSRLQWVLQFOXGHGLQWKHORJOLQHDUUHJUHVVLRQ
Ȝ]6SDQ5DWLR
1$
WLPHSHULRGRYHUZKLFKȜ]ZDVGHWHUPLQHGDVDUDWLRRIW
5DGM
1$
DGMXVWHGFRHIILFLHQWIRUGHWHUPLQDWLRQRIH[SRQHQWLDOILW
:KHUHSRVVLEOHWKHVSDQRIWLPHXVHGLQWKHGHWHUPLQDWLRQRIȜ]LHWKHGLIIHUHQFHEHWZHHQȜ]
8SSHUDQGȜ]/RZHUVKRXOGEHKDOIOLYHV,IWKHȜ]6SDQ5DWLRLVWKHUREXVWQHVVRI
WKHWYDOXHVZLOOEHGLVFXVVHGLQWKH&65
8.5.1.2. Criteria for Calculation and Reporting of Area Under the Concentration-time 
Curve 
7KHPLQLPXPUHTXLUHPHQWIRUWKHFDOFXODWLRQRIDUHDXQGHUWKHFRQFHQWUDWLRQWLPHFXUYH
$8&ZLOOEHWKHLQFOXVLRQRIDWOHDVWFRQVHFXWLYHFRQFHQWUDWLRQVDERYHWKHORZHUOLPLWRI
TXDQWLILFDWLRQ,IWKHUHDUHRQO\FRQVHFXWLYHFRQFHQWUDWLRQVDWOHDVWVKRXOGIROORZ&PD[
,IWKHH[WUDSRODWHGDUHDLV!$8&DQGGHULYHGSDUDPHWHUVPD\EHH[FOXGHGIURP
WKHVXPPDU\VWDWLVWLFVDQGVWDWLVWLFDODQDO\VLVDWWKHGLVFUHWLRQRIWKHVSRQVRURU
SKDUPDFRNLQHWLFLVW
,I$8&FDQQRWEHGHWHUPLQHGUHOLDEO\IRUDOOVXEMHFWVDQGRUWUHDWPHQWVDQDOWHUQDWLYH
$8&PHDVXUHVXFKDV$8&WRDIL[HGWLPHSRLQWRU$8&WPD\EHXVHGLQWKHVWDWLVWLFDO
DQDO\VLV
8.5.1.3. Criteria for Handling Below the Limit of Quantification or Missing 
Concentrations for Pharmacokinetic Analysis 
3ODVPDFRQFHQWUDWLRQVEHORZWKHOLPLWRITXDQWLILFDWLRQ%/4ZLOOEHDVVLJQHGDYDOXHRI
EHIRUHWKHILUVWPHDVXUDEOHFRQFHQWUDWLRQDQGWKHUHDIWHU%/4VZLOOEHWUHDWHGDVPLVVLQJ7KH
IROORZLQJUXOHVDSSO\ZLWKVSHFLDOVLWXDWLRQVGHILQHGEHORZ
Ɣ ,IDQHQWLUHFRQFHQWUDWLRQWLPHSURILOHLV%/4LWZLOOEHH[FOXGHGIURP3.DQDO\VLV
Ɣ :KHUHRUPRUHFRQVHFXWLYHFRQFHQWUDWLRQVDUH%/4DWWKHHQGRIDSURILOHWKHSURILOH
ZLOOEHGHHPHGWRKDYHWHUPLQDWHGDQGDQ\IXUWKHUTXDQWLILDEOHFRQFHQWUDWLRQVZLOOEH
VHWWRPLVVLQJIRUWKHFDOFXODWLRQRIWKH3.SDUDPHWHUVXQOHVVWKH\DUHFRQVLGHUHGWREH
DWUXHFKDUDFWHULVWLFRIWKHSURILOHRIWKHGUXJ
Page 12 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
Ɣ ,ID'D\SUHGRVHSODVPDFRQFHQWUDWLRQLVPLVVLQJLWPD\EHVHWWR]HURE\GHIDXOW
8.5.1.4. Treatment of Outliers in Pharmacokinetic Analysis 
,IDYDOXHLVFRQVLGHUHGWREHDQRPDORXVGXHWREHLQJLQFRQVLVWHQWZLWKWKHH[SHFWHG3.
SURILOHLWPD\EHDSSURSULDWHWRH[FOXGHWKHYDOXHIURPWKH3.DQDO\VLV+RZHYHUWKH
H[FOXVLRQRIDQ\GDWDPXVWKDYHVWURQJMXVWLILFDWLRQDQGZLOOEHGRFXPHQWHGLQWKH&65
$Q\TXDQWLILDEOHSUHGRVHFRQFHQWUDWLRQYDOXHLQWKHILUVWWUHDWPHQWSHULRGZLOOEHFRQVLGHUHG
DQRPDORXVDQGVHWWRPLVVLQJIRUWKH3.DQDO\VLV
,IWKHSUHGRVHFRQFHQWUDWLRQLV!RI&PD[LQWKHVHFRQGWUHDWPHQWSHULRGDOO3.
FRQFHQWUDWLRQDQGSDUDPHWHUGDWDZLOOEHH[FOXGHGIURPWKHVXPPDU\VWDWLVWLFVDQGVWDWLVWLFDO
DQDO\VLVIRUWKDWSHULRG
8.5.2. Presentation of Pharmacokinetic Data 
,IWKHDFWXDOWLPHRIVDPSOHFROOHFWLRQGHYLDWHVIURPWKHQRPLQDOWLPHE\PRUHWKDQ
WKHFRQFHQWUDWLRQZLOOEHIODJJHGDQGH[FOXGHGIURPWKHVXPPDU\VWDWLVWLFV,QGLYLGXDO
FRQFHQWUDWLRQVGHHPHGWREHDQRPDORXVZLOOEHIODJJHGLQWKHOLVWLQJVDQGH[FOXGHGIURPWKH
VXPPDU\VWDWLVWLFV
)RU3.FRQFHQWUDWLRQGDWDWKHIROORZLQJUXOHVZLOODSSO\
Ɣ 9DOXHVWKDWDUH%/4ZLOOEHVHWWRIRUWKHFDOFXODWLRQRIVXPPDU\VWDWLVWLFV
Ɣ $ULWKPHWLFPHDQRUPHGLDQYDOXHVWKDWDUH%/4ZLOOEHSUHVHQWHGDV
Ɣ ,IDQ\%/4UHVXOWVWUHDWHGDVDUHLQDVHULHVRIVXPPDUL]HGGDWDJHRPHWULFPHDQ
DQG&9RIJHRPHWULFPHDQZLOOEHUHSRUWHGDVQRWFDOFXODWHG1&
)RU3.SDUDPHWHUVWKHIROORZLQJUXOHZLOODSSO\
Ɣ *HRPHWULFPHDQDQGFRHIILFLHQWRIYDULDWLRQZLOOQRWEHFDOFXODWHGIRU7PD[RU7ODVW
8.5.3. Pharmacokinetic Statistical Methodology  
$OO3.FRQFHQWUDWLRQVDQGSDUDPHWHUVZLOOEHOLVWHG
6XPPDU\WDEOHVPHDQVWDQGDUGGHYLDWLRQ>6'@ILJXUHVRYHUOD\LQJLQGLYLGXDOILJXUHVDQG
LQGLYLGXDOILJXUHVE\WUHDWPHQWDQGWLPHSRVWGRVHZLOOEHSURYLGHGIRUSODVPD3.
FRQFHQWUDWLRQV$OOILJXUHVZLOOEHSURGXFHGRQERWKOLQHDUDQGVHPLORJDULWKPLFVFDOHV7KH
6'EDUVZLOORQO\EHGLVSOD\HGRQWKHOLQHDUVFDOH
6XPPDU\WDEOHVE\WUHDWPHQWZLOOEHSURYLGHGIRUDOO3.SDUDPHWHUVZLWKWKHH[FHSWLRQRI
GLDJQRVWLFUHJUHVVLRQUHODWHG3.SDUDPHWHUV
$VWDWLVWLFDODQDO\VLVZLOOEHFRQGXFWHGWRLQYHVWLJDWHWKHGUXJGUXJLQWHUDFWLRQRQWKH3.RI
]DQXEUXWLQLEE\FRPSDULQJ]DQXEUXWLQLEFRDGPLQLVWHUHGZLWKULIDEXWLQWHVWWUHDWPHQWWR
]DQXEUXWLQLEDORQHUHIHUHQFHWUHDWPHQWIRU$8&W$8&DQG&PD[
Page 13 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
7KHQDWXUDOORJOQWUDQVIRUPHG3.SDUDPHWHUVZLOOEHDQDO\]HGXVLQJDPL[HGPRGHO7KH
PRGHOZLOOLQFOXGHWUHDWPHQWDVDIL[HGHIIHFWDQGVXEMHFWDVDUDQGRPHIIHFW
)RUHDFK3.SDUDPHWHUVHSDUDWHO\WKHOHDVWVTXDUHVPHDQ/60IRUHDFKWUHDWPHQW
GLIIHUHQFHLQ/60VEHWZHHQWKHWHVWDQGUHIHUHQFHWUHDWPHQWVDQGFRUUHVSRQGLQJ
FRQILGHQFHLQWHUYDO&,ZLOOEHFDOFXODWHGWKHVHYDOXHVZLOOWKHQEHEDFNWUDQVIRUPHGWRJLYH
WKHJHRPHWULFOHDVWVTXDUHPHDQ*/60UDWLRRI*/60VIRU]DQXEUXWLQLEULIDEXWLQ'D\
WR]DQXEUXWLQLEDORQH'D\DQGFRUUHVSRQGLQJ&,
$GGLWLRQDOO\WKHSRROHGHVWLPDWHDFURVVDOOWUHDWPHQWVRIWKHZLWKLQVXEMHFWFRHIILFLHQWRI
YDULDWLRQ&9ZLOOEHFDOFXODWHGDQGUHVLGXDOSORWVZLOOEHSURGXFHGWRDVVHVVWKHDGHTXDF\
RIWKHPRGHOVILWWHG
([DPSOHVRIWKH6$6FRGHWKDWZLOOEHXVHGDUHDVIROORZV
Mixed Model Analysis 
proc mixed data = <data in>; 
  by parcat1n parcat1 pkday paramn param; 
  class trtan aperiod trtseqp usubjid; 
  model lpk = trtan aperiod trtseqp / cl residual ddfm = kr2; 
  lsmeans trtan / cl pdiff = control('1') alpha = 0.1; 
  random intercept / subject = usubjid(trtseqp);  
  ods output lsmeans = <data out>;   
  ods output diffs = <data out>; 
  ods output covparms = <data out>; 
run; 
8.6. Safety and Tolerability Assessments  
8.6.1. Adverse Events  
$OO$(VZLOOEHFRGHGXVLQJWKH0HGLFDO'LFWLRQDU\IRU5HJXODWRU\$FWLYLWLHV0HG'5$
9HUVLRQRUKLJKHULIXSYHUVLRQHGGXULQJWKHVWXG\$OO$(VZLOOEHDVVLJQHGVHYHULW\
JUDGHXVLQJ&RPPRQ7HUPLQRORJ\&ULWHULDIRU$GYHUVH(YHQWV&7&$(9HUVLRQRU
KLJKHULIXSYHUVLRQHGGXULQJWKHVWXG\
$WUHDWPHQWHPHUJHQWDGYHUVHHYHQW7($(ZLOOEHGHILQHGDVDQ$(WKDWVWDUWVGXULQJRU
DIWHUWKHILUVWGRVHRUVWDUWVSULRUWRWKHILUVWGRVHDQGLQFUHDVHVLQVHYHULW\DIWHUWKHILUVWGRVH
$WUHDWPHQWUHODWHG7($(ZLOOEHGHILQHGDVD7($(ZLWKDUHODWLRQVKLSRIUHODWHGWRWKH
VWXG\WUHDWPHQWDVGHWHUPLQHGE\WKHLQYHVWLJDWRU
7KHDVVLJQPHQWRI7($(VWRWUHDWPHQWVZLOOEHDVIROORZV
Ɣ $7($(ZLWKRQVHWGXULQJRUDIWHU'D\GRVLQJDQGSULRUWR'D\GRVLQJZLOOEH
DVVLJQHGWR]DQXEUXWLQLE
Ɣ $7($(ZLWKRQVHWGXULQJRUDIWHU'D\GRVLQJDQGSULRUWR'D\GRVLQJZLOOEH
DVVLJQHGWRULIDEXWLQ
Ɣ $7($(ZLWKRQVHWGXULQJRUDIWHU'D\GRVLQJZLOOEHDVVLJQHGWRULIDEXWLQFR
DGPLQLVWHUHGZLWK]DQXEUXWLQLE
Page 14 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
$OO$(VZLOOEHOLVWHG
7KHIUHTXHQF\RIVXEMHFWVZLWK7($(VDQGWKHQXPEHURI7($(VZLOOEHVXPPDUL]HGIRUWKH
IROORZLQJFDWHJRULHV
Ɣ 7($(VRYHUDOOVHULRXVOHDGLQJWRGLVFRQWLQXDWLRQDQGOHDGLQJWRGHDWKE\WUHDWPHQW
DQGRYHUDOOWRWDOVDIHW\SRSXODWLRQ
Ɣ 7($(VDFFRUGLQJWRPD[LPXPVHYHULW\E\WUHDWPHQWDQGRYHUDOO
Ɣ 7UHDWPHQWUHODWHG7($(VRYHUDOOVHULRXVOHDGLQJWRGLVFRQWLQXDWLRQDQGOHDGLQJWR
GHDWKE\WUHDWPHQWDQGRYHUDOO
Ɣ 7UHDWPHQWUHODWHG7($(VDFFRUGLQJWRPD[LPXPVHYHULW\E\WUHDWPHQWDQGRYHUDOO
7KHIUHTXHQF\RIVXEMHFWVZLOOEHVXPPDUL]HGE\WUHDWPHQWDQGRYHUDOOIRU7($(VDQG
WUHDWPHQWUHODWHG7($(VXVLQJWKHIROORZLQJFODVVLILFDWLRQV
Ɣ 6\VWHPRUJDQFODVVSUHIHUUHGWHUPE\GHFUHDVLQJLQFLGHQFHRIV\VWHPRUJDQFODVVDQG
SUHIHUUHGWHUPZLWKLQV\VWHPRUJDQFODVVRYHUDOO
Ɣ 3UHIHUUHGWHUPE\GHFUHDVLQJLQFLGHQFHRYHUDOO
)RUWKH$(GDWDWKHIROORZLQJUXOHVZLOODSSO\
Ɣ )RUWKHGHULYDWLRQRI7($(VWDWXV,IWKHVWDUWGDWHWLPHRIDQ$(LVLQFRPSOHWHRU
PLVVLQJDQ$(ZLOOEHDVVXPHGWREHD7($(XQOHVVWKHLQFRPSOHWHVWDUWGDWHWLPHRU
WKHHQGGDWHWLPHLQGLFDWHVDQ$(VWDUWHGSULRUWRWKHILUVWGRVH
Ɣ )RUWKHGHULYDWLRQRIWUHDWPHQWUHODWHG7($(VWDWXV,IWKHVWXG\WUHDWPHQWUHODWLRQVKLS
IRUD7($(LVPLVVLQJD7($(ZLOOEHDVVXPHGWREHDWUHDWPHQWUHODWHG7($(
Ɣ )RUWKHFDOFXODWLRQRIVXPPDU\VWDWLVWLFV,IWKHVHYHULW\RID7($(LVPLVVLQJQR
LPSXWDWLRQRIJUDGHZLOOEHSHUIRUPHG7KH$(ZLOORQO\EHFRXQWHGXQGHUWKH´DOO
JUDGHV´FDWHJRU\
Ɣ )RUWKHFDOFXODWLRQRIVXPPDU\VWDWLVWLFV,IDVXEMHFWH[SHULHQFHGPXOWLSOH7($(VZLWK
WKHVDPHSUHIHUUHGWHUPIRUWKHVDPHWUHDWPHQWWKLVZLOOEHFRXQWHGDV7($(IRUWKDW
WUHDWPHQWXQGHUWKHPD[LPXPVHYHULW\UHFRUGHG
8.6.2. Clinical Laboratory Parameters  
$OOFOLQLFDOODERUDWRU\SDUDPHWHUVDQGFKDQJHVIURPEDVHOLQHZLOOEHOLVWHGDQ\YDOXHRXWVLGH
WKHFOLQLFDOUHIHUHQFHUDQJHZLOOEHIODJJHG6HSDUDWHOLVWLQJVZLOOEHSURYLGHGIRUDQ\
SDUDPHWHUIRUZKLFKWKHUHLVDQ\LQGLYLGXDOVXEMHFWYDOXHRXWVLGHWKHUHVSHFWLYHFOLQLFDO
UHIHUHQFHUDQJH
6XPPDU\WDEOHVE\WUHDWPHQWDQGWLPHSRLQWZLOOEHSURYLGHGIRUREVHUYHGYDOXHDQGFKDQJH
IURPEDVHOLQHIRUDOOFOLQLFDOFKHPLVWU\DQGKHPDWRORJ\SDUDPHWHUV
9DOXHVUHFRUGHGDV[[![RU[ZLOOEHGLVSOD\HGLQWKHOLVWLQJVDVUHFRUGHG)RUWKH
GHULYDWLRQRIOLVWLQJIODJVFDOFXODWLRQRIVXPPDU\VWDWLVWLFVDQGSUHVHQWDWLRQLQWKHILJXUHV
[DQG[YDOXHVZLOOEHLPSXWHGWRRQHOHVVYDOXHLQWKHPD[LPXPGHFLPDOSODFHHJ


LPSXWHGWR

ZKHUHDV![DQG[YDOXHVZLOOEHLPSXWHGWRRQHKLJKHUYDOXHLQWKH
Page 15 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
PD[LPXPGHFLPDOSODFH7KHPD[LPXPGHFLPDOSODFHZLOOEHGHWHUPLQHGWREHWKH
PD[LPXPQXPEHURIGHFLPDOSODFHVIURPDOOUHFRUGVRIDSDUDPHWHU
8.6.3. Vital Signs Parameters  
$OOYLWDOVLJQVSDUDPHWHUVDQGFKDQJHVIURPEDVHOLQHZLOOEHOLVWHGDQ\YDOXHRXWVLGHWKH
FOLQLFDOUHIHUHQFHUDQJHZLOOEHIODJJHG
6XPPDU\WDEOHVZLOOEHSURYLGHGIRUREVHUYHGYDOXHDQGFKDQJHIURPEDVHOLQHIRUDOOYLWDO
VLJQVSDUDPHWHUV
8.6.4. 12-lead Electrocardiogram Parameters  
$OOOHDG(&*SDUDPHWHUVDQGFKDQJHVIURPEDVHOLQHZLOOEHOLVWHGDQ\YDOXHRXWVLGHWKH
FOLQLFDOUHIHUHQFHUDQJHZLOOEHIODJJHG
6XPPDU\WDEOHVZLOOEHSURYLGHGIRUREVHUYHGYDOXHDQGFKDQJHIURPEDVHOLQHIRUDOOOHDG
(&*SDUDPHWHUV
8.6.5. Other Assessments  
$OORWKHUVDIHW\DQGWROHUDELOLW\DVVHVVPHQWVQRWGHWDLOHGLQWKHDERYHVHFWLRQVZLOOEHOLVWHG
RQO\
8.6.6. Safety and Tolerability Statistical Methodology  
1RLQIHUHQWLDOVWDWLVWLFDODQDO\VHVDUHSODQQHG
9. INTERIM ANALYSES  
1RLQWHULPDQDO\VHVDUHSODQQHGIRUWKLVVWXG\
10. SIGNIFICANT CHANGES FROM THE PROTOCOL-SPECIFIED ANALYSES  
7KHUHZHUHQRVLJQLILFDQWFKDQJHVIURPWKHSURWRFROVSHFLILHGDQDO\VHV
11. REFERENCES  
 ,&+,&++DUPRQLVHG7ULSDUWLWH*XLGHOLQH6WDWLVWLFDOSULQFLSOHVIRUFOLQLFDOWULDOV(
)HEUXDU\
 ,&+,&++DUPRQLVHG7ULSDUWLWH*XLGHOLQH6WUXFWXUHDQGFRQWHQWRIFOLQLFDOVWXG\UHSRUWV
(1RYHPEHU
 .HHQH217KHORJWUDQVIRUPDWLRQLVVSHFLDOStat Med
 %URZQ+3UHVFRWW5Applied Mixed Models in Medicine&KLFKHVWHU-RKQ:LOH\	
6RQV
Page 16 of 20


6$3
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%
)LQDO9HUVLRQ2&7
3DJHRI
67$'9HUVLRQ
12. APPENDICES 
Appendix 1: 
Document History 
Status, Version 
Date of 
Change 
Summary/Reason for Changes 
)LQDO9HUVLRQ
1$
1$WKHILUVWYHUVLRQ
1$ QRWDSSOLFDEOH


Page 17 of 20


6WDWLVWLFDO$QDO\VLV3ODQ$SSURYDO)RUP

&29$1&(,1&&21),'(17,$/
3DJHRI
6SRQVRU1DPH
%HL*HQH/WG
6SRQVRU3URWRFRO,'
%*%
&RYDQFH6WXG\,'

6$37H[W)LOHQDPH
%HL*HQHB%*%BB6$3B)LQDOB9GRF[
7)/6KHOOV)LOHQDPH
%HL*HQHB%*%BB7)/B6KHOOVB)LQDOB9GRF[
9HUVLRQ

'DWH
2&7


&RYDQFH$SSURYDOV


6LJQDWXUH

'DWH

3ULQWHG1DPH7LWOH



6LJQDWXUH

'DWH

3ULQWHG1DPH7LWOH


6SRQVRU$SSURYDOV
%\ VLJQLQJ EHORZ ZKHQ WKH VWDWLVWLFDO DQDO\VLV SODQ 6$3 LV FRQVLGHUHG ILQDO WKH
VLJQDWRULHVDJUHHWRWKHDQDO\VHVWREHSHUIRUPHGIRUWKLVVWXG\DQGWRWKHIRUPDW
RIWKHDVVRFLDWHGWDEOHVILJXUHVDQGOLVWLQJV7)/V2QFHWKH6$3KDVEHHQVLJQHG
SURJUDPPLQJRIWKH7)/VEDVHGRQWKLVGRFXPHQWFDQSURFHHG$Q\PRGLILFDWLRQVWR
WKH6$3DQG7)/VPDGHDIWHUVLJQLQJPD\UHVXOWLQDZRUNVFRSHFKDQJH


6LJQDWXUH

'DWH

3ULQWHG1DPH7LWOH


6LJQDWXUH

'DWH

3ULQWHG1DPH7LWOH




	









Page 18 of 20


6WDWLVWLFDO$QDO\VLV3ODQ$SSURYDO)RUP

&29$1&(,1&&21),'(17,$/
3DJHRI
3OHDVHVFDQHPDLOFRPSOHWHGIRUPVWRWKH/HDG6WDWLVWLFLDQOLVWHGEHORZ
3ULQWHG1DPH7LWOH

(PDLO


Page 19 of 20


&OLQLFDO6WXG\5HSRUW
&21),'(17,$/
&RYDQFH6WXG\
3URWRFRO5HIHUHQFH%*%

16.1.9.2.
Quality Tolerance Limit Definitions 
1RWDSSOLFDEOH
Page 20 of 20
Final