Conditions: Atopic Dermatitis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 28
Healthy volunteers: yes

Brief summary:
An Open Label, Safety Study to Assess the Potential for Adrenal Suppression Following Treatment with DSXS in Patients with Atopic Dermatitis

Detailed description:
To evaluate the potential of DSXS topical product to suppress HPA axis function in patients with moderate to severe atopic dermatitis.

Arms:
arm 1: active treatment

Interventions: intervention 1: DSXS topical
Intervention descriptions: intervention 1: topical treatment

Protocol document:
Prot_001.pdf: 
&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




7,7/(3$*(
This document is a confidential communication of Novum Pharmaceutical Research Services.  Receipt of 
this document constitutes an agreement by the recipient that no unpublished information contained herein 
will be disclosed without Novum's written approval. 
'UXJ
'HVR[LPHWDVRQH7RSLFDO6SUD\

'HVLJQ
$QRSHQODEHOVDIHW\VWXG\WRDVVHVVWKHSRWHQWLDOIRUDGUHQDO
VXSSUHVVLRQIROORZLQJWUHDWPHQWZLWKGHVR[LPHWDVRQH
WRSLFDOVSUD\LQSDWLHQWVZLWKDWRSLFGHUPDWLWLV
3RSXODWLRQ
3DWLHQWVZLWKDFRQILUPHGGLDJQRVLVRIDWRSLFGHUPDWLWLVZLWK
ERG\VXUIDFHDUHDDIIHFWHG

3DWLHQWVZLOOEHHQUROOHGLQWKHIROORZLQJ&RKRUWV
·
&RKRUW±DJHV\HDUVRIDJH
·
&RKRUW±DJHV\HDUVRIDJH
·
&RKRUW±DJHV\HDUVRIDJH
·
&RKRUW±SDWLHQWVPRQWKV\HDUROG

6SRQVRU
7DUR3KDUPDFHXWLFDOV86$,QF
6N\OLQH'ULYH
+DZWKRUQH1<

3URWRFRO1XPEHU
'6;6D

1RYXP6WXG\1XPEHU


,1'


3URWRFRO'DWH
3URWRFRO'DWH5HY
3URWRFRO'DWH5HY



 
NIIRB
September 13, 2016
APPROVED


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




.(<678'<3(56211(/$1')$&,/,7,(6

6SRQVRU

7DUR3KDUPDFHXWLFDOV86$,QF
6N\OLQH'ULYH
+DZWKRUQH1<


&52

1RYXP3KDUPDFHXWLFDO5HVHDUFK6HUYLFHV1RYXP
:6WDWLRQ6TXDUH'ULYH
3LWWVEXUJK3$


6SRQVRU¶V5HSUHVHQWDWLYH

1DWDOLH<DQWRYVNL\
6HQLRU'LUHFWRU&OLQLFDO5HVHDUFK
7DUR3KDUPDFHXWLFDOV86$,QF
6N\OLQH'ULYH
+DZWKRUQH1<
3KRQH([W
)D[
(PDLO1DWDOLH<DQWRYVNL\#7DURFRP


&52UHSUHVHQWDWLYH

*DLO*RQJDV
9LFH3UHVLGHQW&OLQLFDO7ULDOV
1RYXP3KDUPDFHXWLFDO5HVHDUFK6HUYLFHV
7HO[
)D[
(PDLOJGJRQJDV#QRYXPSUVFRP

0HGLFDO0RQLWRU

3DROR)DQ]LR0'
0HGLFDO0RQLWRU
1RYXP3KDUPDFHXWLFDO5HVHDUFK6HUYLFHV
7HO[
)D[
(PDLOSPIDQ]LR#QRYXPSUVFRP


%LRVWDWLVWLFLDQ

-LDQKXD/LX06F
6HQLRU%LRVWDWLVWLFLDQ
1RYXP3KDUPDFHXWLFDO5HVHDUFK6HUYLFHV
7HO
(PDLOMOLX#QRYXPSUVFRP







9/23/2016
27 Sep 2016


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



35,1&,3$/,19(67,*$725¶66,*1$785(



, BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB DJUHH WR FRQGXFW SURWRFRO '6;6 D 5HY LQ
DFFRUGDQFH ZLWK )'$ UHJXODWLRQV ,&+ JXLGHOLQHV DQG *RRG &OLQLFDO 3UDFWLFH , XQGHUVWDQG WKDW QR
GHYLDWLRQV IURP WKH SURWRFRO PD\ EH PDGH ZLWKRXW WKH SULRU SHUPLVVLRQ RI WKH 6SRQVRU 7DUR
3KDUPDFHXWLFDOV86$RU1RYXP3KDUPDFHXWLFDO5HVHDUFK6HUYLFHVWKHFRPSDQ\PDQDJLQJWKHVWXG\





BBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB


BBBBBBBBBB
3ULQFLSDO,QYHVWLJDWRU






'DWH
























&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI





7$%/(2)&217(176

 
7,7/(3$*( 
 
.(<678'<3(56211(/$1')$&,/,7,(6 
6,*1$785(3$*( 
 
7$%/(2)&217(176 
 
6<1236,6 
 
/,672)$%%5(9,$7,216$1'7(506 
 
,1752'8&7,21 
 
'LVHDVH%HLQJ7UHDWHG 
 
$YDLODELOLW\DQG(IILFDF\RI$OUHDG\$SSURYHG7KHUDSLHV 
 
6FLHQWLILFDQG6WDWLVWLFDO&RQVLGHUDWLRQV 
 
5LVNVDQG%HQHILWV 
 
678'<2%-(&7,9(6 
 
,19(67,*$7,21$/3/$1 
 
6WXG\'HVLJQDQG3ODQ'HVFULSWLRQ 
 
6HOHFWLRQRI6WXG\'HVLJQ 
 
6HOHFWLRQRI6WXG\3RSXODWLRQ 
 
,QFOXVLRQ&ULWHULD 
 
([FOXVLRQ&ULWHULD 
 
5HVWULFWLRQVGXULQJWKH6WXG\ 
 
5HPRYDORI3DWLHQWVIURPWKH6WXG\ 
 
7UHDWPHQWV 
 
7UHDWPHQWV$GPLQLVWUDWLRQ 
 
,GHQWLW\RI,QYHVWLJDWLRQDO3URGXFW 
 
0HWKRGRI$VVLJQLQJ3DWLHQWVWR7UHDWPHQW*URXSV 
 
3DFNDJLQJ 
 
$FFRXQWDELOLW\ 
 
&RPSOLDQFH 
 
6WXG\&RQGXFW 
 
9LVLW'D\6FUHHQLQJ(QUROOPHQW%HIRUHSP 
 
9LVLW'D\,QWHULP9LVLW 


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



9LVLW'D\(QGRI6WXG\RU(DUO\7HUPLQDWLRQ%HIRUHSP 
9LVLW'D\)ROORZXS3KRQH&DOO 
 
6WXG\3URFHGXUHV 
 
,QIRUPHG&RQVHQW 
 
'HPRJUDSKLFV 
 
0HGLFDO+LVWRU\ 
 
9LWDO6LJQV 
 
3K\VLFDO([DPDQG%RG\6XUIDFH$UHD%6$ 
 
'HUPDWRORJLFDO$VVHVVPHQW 
 
&RQFRPLWDQW0HGLFDWLRQ8VH 
 
3UHJQDQF\7HVW 
 
'LVSHQVLQJ6WXG\'UXJ 
 
&ROOHFWLQJ6WXG\'UXJ 
 
'RVLQJ,QVWUXFWLRQVDQG'LDU\ 
 
'RVLQJ&RPSOLDQFH 
 
6WDQGDUG6XQVFUHHQDQG3DWLHQW:ULVWEDQG 
 
/DERUDWRU\(YDOXDWLRQ 
 
&RUWLVRO5HVSRQVH7HVW 
 
$GYHUVH(YHQWV 
 
$GYHUVH(YHQW'HILQLWLRQV 
 
6HYHULW\RI$GYHUVH(YHQW 
 
5HODWLRQVKLSRI$GYHUVH(YHQW 
 
3DWLHQW¶V3DUWLFLSDWLRQ6WRSSLQJ&ULWHULD 
 
6HULRXV$GYHUVH(YHQWV 
 
'HILQLWLRQRID6HULRXV$GYHUVH(YHQW 
 
5HSRUWLQJ6HULRXV$GYHUVH(YHQWV 
 
67$7,67,&$/0(7+2'6 
 
6WDWLVWLFDO3ODQ 
 
'HWHUPLQDWLRQRI6DPSOH6L]H 
 
%DVHOLQH&RPSDUDELOLW\ 
 
6DIHW\$QDO\VLVRI3RWHQWLDO+3$$[LV6XSSUHVVLRQ 
 
6DIHW\$QDO\VLV 
 
5(*8/$725<2%/,*$7,216 


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



 
,QVWLWXWLRQDO5HYLHZ%RDUG 
 
6WXG\'RFXPHQWDWLRQ 
 
3URWRFRO 
 
,QIRUPHG&RQVHQW 
 
3URWRFRODQG,QIRUPHG&RQVHQW&KDQJHV 
 
6RXUFH'RFXPHQWVDQG&DVH5HSRUW)RUPV 
 
'UXJ$FFRXQWDELOLW\ 
 
'UXJ6WRUDJH 
 
3UHJQDQFLHV 
 
5HSRUWLQJ6DIHW\,QIRUPDWLRQWRWKH,5% 
 
5HFRUG5HWHQWLRQ 
 
6WXG\0RQLWRULQJDQG$XGLWLQJ 
 
(QGRIWKH7ULDO 
 
&OLQLFDO6WXG\5HSRUW 
 
5()(5(1&(6 
 
$33(1',&(6 
$33(1',;$%RG\6XUIDFH$UHD&DOFXODWLRQ 
$33(1',;%(F]HPD$UHDDQG6HYHULW\,QGH[6FRUH($6, 
$33(1',;&,QYHVWLJDWRU*OREDO$VVHVVPHQW,*$ 
$33(1',;'$SSOLFDWLRQ6LWH5HDFWLRQV 
$33(1',;(&RUWLVRO5HVSRQVH7HVW 
$33(1',;)(YDOXDWLRQRI+3$$[LV6XSSUHVVLRQ 
$33(1',;*&OLQLFDO/DERUDWRU\7HVWLQJ 
$33(1',;+&RUWURV\Q3DFNDJH,QVHUW 
$33(1',;,,QYHVWLJDWRU%URFKXUH'HVR[LPHWDVRQH7RSLFDO6SUD\ 
$33(1',;-3URWRFRO5HYLVLRQV 




&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




6<1236,6

3URWRFRO1XPEHU
'6;6D
7LWOH
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ
)ROORZLQJ 7UHDWPHQW ZLWK 'HVR[LPHWDVRQH  7RSLFDO 6SUD\ 7DUR
3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV
2EMHFWLYHV
 7KHREMHFWLYHRIWKLVVWXG\LVWRHYDOXDWHWKHSRWHQWLDORIGHVR[LPHWDVRQH
WRSLFDOVSUD\WRVXSSUHVV+3$D[LVIXQFWLRQLQSDWLHQWVZLWK
PRGHUDWHWRVHYHUHDWRSLFGHUPDWLWLV
 7KHVHFRQGDU\REMHFWLYHVDUHWRHYDOXDWHWRHYDOXDWHWKHHIILFDF\
SDUDPHWHUVDQGDGYHUVHHYHQW$(SURILOHVRIGHVR[LPHWDVRQH
WRSLFDOVSUD\DGPLQLVWHUHGWRSDWLHQWVZLWKPRGHUDWHWRVHYHUHDWRSLF
GHUPDWLWLV
6SRQVRU
7DUR3KDUPDFHXWLFDOV86$,QF
1DPHRI7HVW
3URGXFW
'HVR[LPHWDVRQH7RSLFDO6SUD\
5RXWHRI
$GPLQLVWUDWLRQ
7RSLFDO
6WXG\'HVLJQ
$Q RSHQ ODEHO VDIHW\ VWXG\ WR DVVHVV WKH SRWHQWLDO IRU DGUHQDO VXSSUHVVLRQ
IROORZLQJWUHDWPHQWZLWKGHVR[LPHWDVRQHWRSLFDOVSUD\DGPLQLQVWHUHG
WZLFHGDLO\IRUGD\VLQSDWLHQWVZLWKPRGHUDWHWRVHYHUHDWRSLFGHUPDWLWLV
6WXG\3RSXODWLRQ
$SSUR[LPDWHO\WZHQW\ILYHWRILIW\SDWLHQWVVWUDWLILHGE\DJHZLWKD
FRQILUPHGGLDJQRVLVRIPRGHUDWHWRVHYHUHDWRSLFGHUPDWLWLVZLWK
&RKRUW±SDWLHQWVDJH\HDUVRIDJHZLWKERG\VXUIDFH
DUHD%6$DIIHFWHG
&RKRUW±SDWLHQWVDJH\HDUVRIDJHZLWKERG\VXUIDFH
DUHD%6$DIIHFWHG
&RKRUW±SDWLHQWVDJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD
%6$DIIHFWHG
&RKRUW±SDWLHQWVPRQWKV\HDURIDJHZLWKERG\VXUIDFH
DUHD%6$DIIHFWHG

&RKRUWVZLOOEHHQUROOHGLQVHTXHQWLDORUGHU(DFKFRKRUWZLOOLQLWLDWH
HQUROOPHQWRQFHWKHSUHYLRXVFRKRUWKDVUHDFKHGWKHPLQLPXPQXPEHURI
SDWLHQWVDQGDVDIHW\DQDO\VLVKDVEHHQUHYLHZHG(DFKFRKRUWZLOOEH
HQUROOHGEDVHGRQWKHDYDLODELOLW\RISDWLHQWV

(DFKFRKRUWZLOOEHUHYLHZHGIRUWKHSRWHQWLDORI+3$D[LVVXSSUHVVLRQ,IDW


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



OHDVWRISDWLHQWVLQHDFK&RKRUWH[SHULHQFH+3$D[LVVXSSUHVVLRQRQFH
WKHPLQLPXPQXPEHURISDWLHQWVKDVEHHQHQUROOHGDQGFRPSOHWHGWKHFRKRUW
HQUROOPHQWIRUWKDWFRKRUWZLOOEHVWRSSHGDQGQRIXUWKHUFRKRUWVZLOOEH
LQLWLDWHG,IDWOHDVWRISDWLHQWVKDYHH[SHULHQFHG+3$D[LVVXSSUHVVLRQ
DFURVVFRKRUWVFRPELQHGGXULQJWKHVWXG\HQUROOPHQWZLOOEHGLVFRQWLQXHG
DQGQRRWKHUFRKRUWVZLOOEHLQLWLDWHG&RKRUWZLOOQRWEHJLQXQWLOVDIHW\
GDWDKDVEHHQUHYLHZHGIRU&RKRUW7KHVDPHSURFHVVZLOOEHIROORZHGIRU
HDFK&RKRUWXQWLOWKHVWXG\LVFRPSOHWH
7KHHQUROOPHQWLQWKHLQGLYLGXDO&RKRUWPD\QRWUHTXLUHLIWKHVDWLVIDFWRU\
VDIHW\GDWDIRUWKHVDPHDJHJURXSZDVREWDLQHGLQWKHVWXG\'6;6
6WXG\&RQGXFW
$OOSDWLHQWVZLOODWWHQGWKHFOLQLFIRUVFKHGXOHGYLVLWV
9LVLW6FUHHQLQJ(QUROOPHQW'D\
9LVLW,QWHULP9LVLW'D\
9LVLW(QGRI6WXG\'D\RU(DUO\7HUPLQDWLRQ
,QFOXVLRQ&ULWHULD
 0DOHRUQRQSUHJQDQWQRQODFWDWLQJIHPDOHV
·
&RKRUW±DJHV\HDUVRIDJH
·
&RKRUW±DJHV\HDUVRIDJH
·
&RKRUW±DJHV\HDUVRIDJH
·
&RKRUW±SDWLHQWVPRQWKV\HDURIDJH
 ,IIHPDOHDQGRIFKLOGEHDULQJSRWHQWLDOSUHSDUHGWRDEVWDLQIURPVH[XDO
LQWHUFRXUVH RU XVH D UHOLDEOH PHWKRG RI FRQWUDFHSWLRQ GXULQJ WKH VWXG\
HJ
FRQGRP
,8'
RUDO
WUDQVGHUPDO
RU
LQMHFWHG
KRUPRQDO
FRQWUDFHSWLYHV
 3DUHQWOHJDOJXDUGLDQKDVVLJQHGLQIRUPHGFRQVHQWIRUPZKLFKPHHWVDOO
FULWHULDRIFXUUHQW)'$UHJXODWLRQV
 %DVHG RQ WKH SDWLHQW¶V DJH   \HDU ROGV ZLOO UHDG DQG VLJQ DQ ,5%
DSSURYHGDVVHQWIRUP3DWLHQWV\HDUVRIDJHZLOOSURYLGHYHUEDODVVHQW
WRSDUWLFLSDWH
 3DWLHQWVZLWKDGHILQLWHFOLQLFDOGLDJQRVLVRIVWDEOHDWRSLFGHUPDWLWLVZLWK
LQYROYHPHQWRI
·
&RKRUW±DJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD
%6$DIIHFWHGH[FOXGLQJIDFHD[LOODDQGJURLQDUHDV
·
&RKRUW±DJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD
%6$DIIHFWHGH[FOXGLQJIDFHD[LOODDQGJURLQDUHDV
·
&RKRUW±DJH\HDUVRIDJHZLWKZLWKERG\VXUIDFHDUHD
%6$DIIHFWHGH[FOXGLQJIDFHD[LOODDQGJURLQDUHDV
·
&RKRUW±PRQWKV\HDURIDJHZLWKERG\VXUIDFHDUHD
%6$DIIHFWHGH[FOXGLQJIDFHD[LOODDQGJURLQDUHDV
 +DYHDQ(F]HPD$UHDDQG6HYHULW\,QGH[($6,VFRUHRIDWOHDVW
 +DYHDQ,QYHVWLJDWRU*OREDO$VVHVVPHQW6FDOH,*$RI0RGHUDWHRU
6HYHUH


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



([FOXVLRQ&ULWHULD
 )HPDOHVZKRDUHSUHJQDQWQXUVLQJSODQQLQJWREHFRPHSUHJQDQWGXULQJ
WKH GXUDWLRQ RI WKH VWXG\ RU LI RI FKLOGEHDULQJ SRWHQWLDO DQG VH[XDOO\
DFWLYHDQGQRWSUHSDUHGWRXVHDSSURSULDWHFRQWUDFHSWLYHPHWKRGVWRDYRLG
SUHJQDQF\
 /DFNVVWDEOHGLDJQRVLVRIDWRSLFGHUPDWLWLVRUKDVEHHQGLDJQRVHGZLWK
PLOGDWRSLFGHUPDWLWLV
 +DYHDQ($6,VFRUHRI
 +DYHDQ,*$VFRUHRI
 $WRSLFGHUPDWLWLVZLWKD%6$LQYROYHPHQWRIRU
 $FWLYH FXWDQHRXV EDFWHULDO RU YLUDO LQIHFWLRQ LQ DQ\ WUHDWPHQW DUHD DW
EDVHOLQHLHFOLQLFDOO\LQIHFWHGDWRSLFGHUPDWLWLV
 3DWLHQWKDVDKLVWRU\RIDWRSLFGHUPDWLWLVWKDWKDVEHHQXQUHVSRQVLYHWR
WRSLFDOFRUWLFRVWHURLGWKHUDS\
 $Q\ FRQGLWLRQ LH VXQEXUQ SVRULDVLV HWF WKDW LQ WKH ,QYHVWLJDWRU¶V
RSLQLRQ PD\ LQWHUIHUH ZLWK WKH FOLQLFDO DVVHVVPHQWV RI WKH VLJQV DQG
V\PSWRPVRIDWRSLFGHUPDWLWLV
 3DWLHQWKDVDKLVWRU\RIDOOHUJ\RUVHQVLWLYLW\WRFRUWLFRVWHURLGVRUKLVWRU\
RIDQ\GUXJK\SHUVHQVLWLYLW\RULQWROHUDQFHZKLFKLQWKHRSLQLRQRIWKH
,QYHVWLJDWRUZRXOGFRPSURPLVHWKHVDIHW\RIWKHSDWLHQWRUWKHUHVXOWVRI
WKHVWXG\
3DWLHQWKDVDVLJQLILFDQWKLVWRU\RUFXUUHQWHYLGHQFHRIFKURQLFLQIHFWLRXV
GLVHDVHV\VWHPGLVRUGHURUJDQGLVRUGHURURWKHUPHGLFDOFRQGLWLRQWKDW
LQWKH,QYHVWLJDWRU¶VRSLQLRQZRXOGSODFHWKHVWXG\SDWLHQWDWXQGXHULVN
E\SDUWLFLSDWLRQLQWKHVWXG\
3DWLHQWLVFXUUHQWO\UHFHLYLQJRUKDVUHFHLYHGDQ\UDGLDWLRQWKHUDS\DQWL
QHRSODVWLF DJHQWV RU LPPXQRVXSSUHVVDQW PHGLFDWLRQ ZLWKLQ  ZHHNV
EHIRUHWKHILUVWGRVHRIVWXG\GUXJ
8VH ZLWKLQ RQH PRQWK EHIRUH EDVHOLQH RI  RUDO RU LQWUDYHQRXV
FRUWLFRVWHURLGV  89$89% WKHUDS\  389$ SVRUDOHQ SOXV
XOWUDYLROHW $ WKHUDS\  WDQQLQJ ERRWKV  QRQSUHVFULSWLRQ 89 OLJKW
VRXUFH  LPPXQRPRGXODWRUV RU LPPXQRVXSSUHVVLYH WKHUDSLHV 
LQWHUIHURQF\WRWR[LFGUXJVWDFUROLPXVRUSLPHFUROLPXV
8VH ZLWKLQ  GD\V EHIRUH EDVHOLQH RI  V\VWHPLF DQWLELRWLFV 
FDOFLSRWULHQHRURWKHU9LWDPLQ'SUHSDUDWLRQVRUUHWLQRLGV
3DWLHQWV ZKR KDYH XVHG WRSLFDO WUHDWPHQWV SUHVFULSWLRQ RU RYHU WKH
FRXQWHULQFOXGLQJ
D $Q\WRSLFDODWRSLFGHUPDWLWLVWKHUDSHXWLFDJHQWVRIDQ\NLQGZLWKLQ
WKHZHHNVEHIRUHILUVWXVHRIVWXG\GUXJ
E $Q\WRSLFDOFRUWLFRVWHURLGVZLWKLQWKHZHHNVEHIRUHWKHILUVWXVH
RIWKHVWXG\GUXJ
F $Q\DQWLEDFWHULDOPHGLFDWHGDQGRUDVWULQJHQWZDVKHVVRDSVSDGV
RUPRLVWXUL]HUVZLWKLQWKHGD\VEHIRUHWKHILUVWXVHRIVWXG\GUXJ
G +LJKVWUHQJWKRUDERYHDOSKDK\GUR[\DFLGRUDQ\NLQGRI
SHHO RU RWKHU SURFHGXUHV RQ WKH IDFH HJ ODVHU KDLU UHPRYDO
ZLWKLQGD\VRIWKHVWXG\VWDUW
H $Q\WRSLFDOSURGXFWVLHVXQVFUHHQVORWLRQVFUHDPVH[FHSWIRU


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



EODQGHPROOLHQWPRLVWXUL]HUZLWKLQKRXUEHIRUHEDVHOLQH
I 7RSLFDO DQWLELRWLFV LQ WKH WUHDWPHQW DUHD ZLWKLQ  GD\V EHIRUH
EDVHOLQH
3DWLHQWKDVEHHQWUHDWHGZLWKLQZHHNVRUILYHKDOIOLYHVZKLFKHYHULV
OHVVEHIRUHWKHILUVWGRVHRIVWXG\GUXJZLWKDQ\ELRORJLFDOWKHUDSLHVIRU
DWRSLFGHUPDWLWLV
8VH RI QRQVHGDWLQJ DQWLKLVWDPLQHV ZLWKLQ WKH  GD\V EHIRUH WKH ILUVW
GRVLQJGD\
7KHXVHRIVHGDWLQJDQWLKLVWDPLQHVVXFKDVGLSKHQK\GUDPLQHPD\EH
DFFHSWDEOHRQFRQGLWLRQWKHSDWLHQWKDVEHHQRQDVWDEOHGRVHIRUDWOHDVW
GD\VEHIRUHWKHVWXG\VWDUWDQGZLOOUHPDLQRQDVWDEOHGRVHWKURXJKRXW
WKHVWXG\
$Q\RUDOVWHURLGGUXJXVHZLWKWKHH[FHSWLRQFRQWUDFHSWLYHVZLWKLQ
GD\VRIWKHILUVWGRVLQJGD\RUGXULQJWKHVWXG\
D )HPDOHSDWLHQWVXVLQJKRUPRQDOFRQWUDFHSWLYHVVKRXOGKDYH
EHHQRQWKHVDPHSURGXFWGRVLQJUHJLPHQIRUDWOHDVWGD\V
EHIRUHDQGVKRXOGQRWFKDQJHWKLVUHJLPHQGXULQJWKHVWXG\
E 7KHXVHRILQKDOHGRULQWUDQDVDOFRUWLFRVWHURLGVLVDFFHSWDEOH
DVORQJDVXVDJHKDVEHHQVWDEOHIRUDWOHDVWZHHNVEHIRUH
WKHILUVWGRVHRIVWXG\GUXJDQGZLOOEHFRQWLQXHGGXULQJWKH
VWXG\
,QDELOLW\WRXQGHUVWDQGWKHSURWRFROUHTXLUHPHQWVLQVWUXFWLRQVDQGVWXG\
UHODWHGUHVWULFWLRQVWKHQDWXUHVFRSHDQGSRVVLEOHFRQVHTXHQFHVRIWKH
FOLQLFDOVWXG\
8QOLNHO\ WR FRPSO\ ZLWK WKH SURWRFRO UHTXLUHPHQWV LQVWUXFWLRQV DQG
VWXG\UHODWHG UHVWULFWLRQV VXFK DV XQFRRSHUDWLYH DWWLWXGH LQDELOLW\ WR
UHWXUQIRUIROORZXSYLVLWVDQGLPSUREDELOLW\RIFRPSOHWLQJWKHFOLQLFDO
VWXG\
5HFHLSWRIDQ\GUXJDVSDUWRIDUHVHDUFKVWXG\ZLWKLQGD\VSULRUWR
ILUVWGRVLQJ
7KHSDWLHQWLVDPHPEHURIWKHLQYHVWLJDWLRQDOVWXG\VWDIIRUDPHPEHURI
WKHIDPLO\RIWKHLQYHVWLJDWLRQDOVWXG\VWDII
3UHYLRXVSDUWLFLSDWLRQLQWKLVVWXG\LQFOXGLQJSDWLHQWVSUHYLRXVO\HQUROOHG
LQ'6;6
&ULWHULDIRU
(YDOXDWLRQ
3ULPDU\2XWFRPH0HDVXUHV
+\SRWKDODPLF 3LWXLWDU\ $GUHQDO +3$ $[LV 5HVSRQVH WR &RV\QWURSLQ
GHPRQVWUDWLQJWKHDEVHQFHRUSUHVHQFHRIDGUHQDOVXSSUHVVLRQDWWKHHQGRI
WUHDWPHQW
6HFRQGDU\2XWFRPH0HDVXUHV
+\SRWKDODPLF 3LWXLWDU\ $GUHQDO +3$ $[LV 5HVSRQVH WR &RV\QWURSLQ
GHPRQVWUDWLQJ WKH SUHVHQFH RI DGUHQDO VXSSUHVVLRQ DW WKH HQG RI WUHDWPHQW
ZLWK%6$DVDFRYDULDWH


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



+3$$[LV
(YDOXDWLRQ
3ULRUWRWKHILUVWGRVHRIVWXG\GUXJDQGDWWKHHQGRIWKHVWXG\'D\RU
HDUO\ WHUPLQDWLRQ DOO SDWLHQWV ZLOO KDYH D FRUWLVRO UHVSRQVH WHVW SHUIRUPHG
XVLQJWKHSURFHGXUHRI:RRGHWDO6HH$SSHQGL[(2QO\WKRVHSDWLHQWV
ZLWKQRUPDODGUHQDOIXQFWLRQDWEDVHOLQHZLOOEHHQUROOHGDQGGLVSHQVHGVWXG\
GUXJ,IDWWKHHQGRIWKHVWXG\WKHSDWLHQWKDVDFRUWLVROUHVSRQVHWHVWWKDWLV
VXJJHVWLYH RI +3$ D[LV VXSSUHVVLRQ WKH\ ZLOO KDYH D IROORZ WHVW DW OHDVW
HYHU\  ZHHNV XQWLO VXFK WLPH DV WKH ,QYHVWLJDWRU FRQVLGHUV WKH DGUHQDO
IXQFWLRQKDVWXUQHGWRQRUPDO
&RKRUWV ZLOO EH HQUROOHG LQ VHTXHQWLDO RUGHU  (DFK FRKRUW ZLOO LQLWLDWH
HQUROOPHQW RQFH WKH SUHYLRXV FRKRUW KDV UHDFKHG WKH PLQLPXP QXPEHU RI
SDWLHQWV DQG D VDIHW\ DQDO\VLV KDV EHHQ UHYLHZHG  (DFK FRKRUW ZLOO EH
HQUROOHGEDVHGRQWKHDYDLODELOLW\RISDWLHQWV

(DFKFRKRUWZLOOEHUHYLHZHGIRUWKHSRWHQWLDORI+3$D[LVVXSSUHVVLRQ,IDW
OHDVW  RI SDWLHQWV LQ HDFK &RKRUW H[SHULHQFH +3$ D[LV VXSSUHVVLRQ
HQUROOPHQW IRU WKDW FRKRUW ZLOO EH VWRSSHG DQG QR IXUWKHU FRKRUWV ZLOO EH
LQLWLDWHG,IDWOHDVWRISDWLHQWVKDYHH[SHULHQFHG+3$D[LVVXSSUHVVLRQ
DFURVV FRKRUWV FRPELQHG GXULQJ WKH VWXG\ HQUROOPHQW ZLOO EH GLVFRQWLQXHG
DQGQRRWKHUFRKRUWVZLOOEHLQLWLDWHG&RKRUWZLOOQRWEHJLQXQWLOVDIHW\
GDWDKDVEHHQUHYLHZHGIRU&RKRUW7KHVDPHSURFHVVZLOOEHIROORZHGIRU
HDFK&RKRUWXQWLOWKHVWXG\LVFRPSOHWH
3ULPDU\$QDO\VLV
3URSRUWLRQ RI SDWLHQWV LQ WKH VWXG\ ZLWK +3$ D[LV VXSSUHVVLRQ IROORZLQJ
WUHDWPHQWZLWKWKHVWXG\PHGLFDWLRQ
6HFRQGDU\$QDO\VLV
$ORJLVWLFUHJUHVVLRQRIWKHSURSRUWLRQRISDWLHQWVLQWKHVWXG\ZLWK+3$D[LV
VXSSUHVVLRQZLOOEHSHUIRUPHGZLWK%6$DIIHFWHGDVDFRYDULDWH

6DIHW\3DUDPHWHUV
$GYHUVH HYHQWV ZLOO EH FODVVLILHG XVLQJ VWDQGDUG 0HG'5$ WHUPLQRORJ\
9HUVLRQRUKLJKHUDQGVXPPDUL]HGE\WUHDWPHQWJURXS6XPPDU\WDEOHV
FRPSDULQJ WKH W\SH LQFLGHQFH VHYHULW\ DQG ,QYHVWLJDWRU¶V RSLQLRQ RI
UHODWLRQVKLSWRWKHVWXG\GUXJZLOOEHSUHSDUHGE\WUHDWPHQWJURXS6LJQVDQG
V\PSWRPVRIDWRSLFGHUPDWLWLVZLOOQRWEHFRQVLGHUHGDGYHUVHHYHQWVXQOHVV
LQ WKH ,QYHVWLJDWRU¶V RSLQLRQ WKH\ KDYH LQFUHDVHG LQ IUHTXHQF\ DQGRU
VHYHULW\WRVXFKDQH[WHQWWKDWWKH,QYHVWLJDWRUSDWLHQWFRQVLGHUVWKDWLWLVLQ
WKHSDWLHQW¶VEHVWLQWHUHVWWREHGURSSHGIURPFRQWLQXHGSDUWLFLSDWLRQLQWKH
VWXG\DQGJLYHQDOWHUQDWLYHWKHUDS\IRUWKHLUFRQGLWLRQ
,IVXIILFLHQWGDWDH[LVWDGYHUVHHYHQWIUHTXHQFLHVZLOOEHFRPSDUHGEHWZHHQ
WUHDWPHQWVXVLQJ)LVKHU¶VH[DFWWHVWRUDVLPLODUWHVW&RQFRPLWDQWPHGLFDWLRQ
XVHGXULQJWKHVWXG\ZLOOEHWDEXODWHGE\SDWLHQW
$GYHUVH HYHQWV UHSRUWHG GXULQJ WKH VWXG\ ZLOO EH WDEXODWHG LQ D VXPPDU\


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



WDEOHOLVWLQJWKHW\SHLQFLGHQFHVHYHULW\DQG,QYHVWLJDWRU¶VRSLQLRQWRGUXJ
UHODWLRQVKLS
6DPSOH6L]H
'HWHUPLQDWLRQ
7KH VDPSOH VL]H RI  WR  SDWLHQWV VWUDWLILHG E\ DJH DQG  %6$ ZDV
GHWHUPLQHGWREHVXIILFLHQWIRUWKLVVWXG\









&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




678'<6&+(0$7,&

9LVLW
9LVLW
9LVLW
9LVLW
'D\




3URFHGXUHV
(QUROOPHQW

%HIRUHSP
,QWHULP
9LVLW
(QGRI
6WXG\(DUO\
7HUPLQDWLRQ
%HIRUHSP
7HOHSKRQH
)ROORZ8S
9LVLW
,QIRUPHG&RQVHQW
;



0HGLFDO+LVWRU\DQG
'HPRJUDSKLFV
;



9LWDO6LJQV
;
;
;

3UHJQDQF\7HVW
;
;
;

3K\VLFDO([DP
;

;

%6$$VVHVVPHQW
;
;
;

,*$6FRUH
;
;
;

($6,6FRUH
;
;
;

$SSOLFDWLRQ6LWH
5HDFWLRQV
;
;
;

&RQFRPLWDQW
0HGLFDWLRQ
;
;
;

/DERUDWRU\(YDOXDWLRQV
;

;

&RUWLVRO5HVSRQVH7HVW
;

;

&RQILUP
,QFOXVLRQ([FOXVLRQ
&ULWHULD
;



'LVSHQVH6XQVFUHHQ
DQG:ULVWEDQG
;



:HLJKDQG'LVSHQVH
6WXG\'UXJ
;
;


&ROOHFWDQG:HLJK
6WXG\'UXJ

;
;

'LVSHQVH5HYLHZ
3DWLHQW'LDU\
;
;
;

$GYHUVH(YHQWV

;
;
;
(YDOXDWLRQRI3DWLHQW
&RPSOLDQFHWRWKH
3URWRFRO

;
;

3UHJQDQF\WHVWZLOOEHFDUULHGRXWIRUIHPDOHVRIFKLOGEHDULQJSRWHQWLDO



&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




/,672)$%%5(9,$7,216$1'7(506

$EEUHYLDWLRQ 7HUP
$'/
$FWLYLWLHVIRU'DLO\/LYLQJ
$'5
$GYHUVH'UXJ5HDFWLRQ
$(
$GYHUVH(YHQW
%3
%ORRG3UHVVXUH
&
&HOVLXV
&5)
&DVH5HSRUW)RUP
&52
&OLQLFDO5HVHDUFK2UJDQL]DWLRQ
H&7'
HOHFWURQLF&RPPRQ7HFKQLFDO'RFXPHQW
)'$
)RRGDQG'UXJ$GPLQLVWUDWLRQ
+5
+HDUW5DWH
+57
+RUPRQH5HSODFHPHQW7KHUDS\
,&)
,QIRUPHG&RQVHQW)RUP
,&+
,QWHUQDWLRQDO&RQIHUHQFHRQ+DUPRQL]DWLRQ
,*$
,QYHVWLJDWRU¶V*OREDO$VVHVVPHQW
,1'
,QYHVWLJDWLRQDO1HZ'UXJ
,5%
,QVWLWXWLRQDO5HYLHZ%RDUG
,77
,QWHQWWR7UHDW
,8'
,QWUDXWHULQH'HYLFH
/2&)
/DVW2EVHUYDWLRQ&DUULHG)RUZDUG
PO
0LOOLOLWHU
P,77
0RGLILHG,QWHQWWR7UHDW
1'$
1HZ'UXJ$SSOLFDWLRQ
16$,'
1RQ6WHURLGDO$QWL,QIODPPDWRU\'UXJ
2+53
2IILFHRI+XPDQ5LJKWV3URWHFWLRQ
27&
2YHUWKH&RXQWHU
389$
3VRUDOHQDQG8OWUD9LROHW$
55
5HVSLUDWRU\5DWH
6$(
6HULRXV$GYHUVH(YHQW
6$3
6WDWLVWLFDO$QDO\VLV3ODQ
86$
8QLWHG6WDWHVRI$PHULFD





&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




,1752'8&7,21
7DUR 3KDUPDFHXWLFDOV 86$ ,QF 7DUR SODQV WR VXEPLW DQ ,QYHVWLJDWLRQDO 1HZ 'UXJ
$SSOLFDWLRQ ,1' IRU D QHZ IRUPXODWLRQ RI GHVR[LPHWDVRQH GHVR[LPHWDVRQH  WRSLFDO
VSUD\7KLVSURGXFWFRQWDLQVDSRWHQWFRUWLFRVWHURLGWREHLQGLFDWHGIRUWKHWUHDWPHQWRISDWLHQWV
ZLWKPRGHUDWHWRVHYHUHDWRSLFGHUPDWLWLV

'LVHDVH%HLQJ7UHDWHG
$WRSLFGHUPDWLWLV$'FRPPRQO\NQRZQDVHF]HPDLVDFKURQLFLQIODPPDWRU\VNLQFRQGLWLRQ
DIIHFWLQJDSSUR[LPDWHO\PLOOLRQSHRSOHLQWKH8QLWHG6WDWHV,WLVFKDUDFWHUL]HGE\LWFK\
HU\WKHPDWRXVDQGVFDO\VNLQOHVLRQVRIWHQORFDOL]HGWRWKHIOH[XUDOVXUIDFHVRIWKHERG\LQFOXGLQJ
QHFN H\HOLGV IRUHKHDG IDFH ZULVWV GRUVD RI WKH IHHW DQG KDQGV $' LV DOVR DVVRFLDWHG ZLWK
VHFRQGDU\VNLQLQIHFWLRQVZLWKS. aureusDQGKHUSHVVLPSOH[YLUXV+692QVHWRI$'W\SLFDOO\
RFFXUVDWDQHDUO\DJHDQGDVXUYH\RIFKLOGUHQLQWKH8QLWHG6WDWHVHVWLPDWHGDQRYHUDOO
SUHYDOHQFHRIDSSUR[LPDWHO\DQGDVKLJKDVLQVRPHVWDWHV,QWKH8QLWHG6WDWHVDORQH
LWLVHVWLPDWHGWKDWPRUHWKDQPLOOLRQSHU\HDULVVSHQWRQWKHWUHDWPHQWRIFKLOGKRRGDWRSLF
GHUPDWLWLV
$'FDQSUHVHQWLQWKUHHFOLQLFDOSKDVHVYL]DFXWHVXEDFXWHDQGFKURQLF,WFDQEHGLIIHUHQWLDOO\
GLDJQRVHGDVFRQWDFWGHUPDWLWLVFDQGLGLDVLVSVRULDVLVVFDELHVLPSHWLJRHWFGXHWRLWVDSSHDUDQFH
DQGSUHVHQWDWLRQRQVNLQ'LDJQRVLVRI$'LVEDVHGRQKLVWRU\DQGSK\VLFDOH[DPLQDWLRQ7KHUH
DUH PDQ\ SURSRVHG GLDJQRVWLF FULWHULD KRZHYHU D  V\VWHPDWLF UHYLHZ FRQFOXGHG WKDW WKH
8.:RUNLQJ3DUW\¶V'LDJQRVWLF&ULWHULDDUHWKHPRVWH[WHQVLYHO\YDOLGDWHG7KHPRVWLPSRUWDQW
IHDWXUHVFRQVLGHUHGIRU$'GLDJQRVLVDUHSUXULWXVHF]HPDERG\VXUIDFHDUHDLQYROYHPHQWDQG
SDWWHUQDORQJZLWKPHGLFDOKLVWRU\DQGDVVRFLDWHGIHDWXUHV$FRPPRQO\XVHGGLVHDVHVHYHULW\
VFDOH IRU FOLQLFDO VWXGLHV LQ $' LV WKH (F]HPD $UHD DQG 6HYHULW\ ,QGH[ ($6, ZKLFK XVHV
REMHFWLYH SK\VLFLDQ HVWLPDWHV RI GLVHDVH H[WHQW DQG VHYHULW\ 7KH ,QYHVWLJDWRU¶V *OREDO
$VVHVVPHQW,*$LVDOVRXVHGW\SLFDOO\DVDVWDWLFPHDVXUHWRVFRUHWKHVHYHULW\RIVLJQVDQG
V\PSWRPVRI$'
5HFHQW UHVHDUFK LQGLFDWHV WKDW VRPH RI WKH FDXVDWLYH IDFWRUV IRU $' LQFOXGH DQ LPSDLUHG VNLQ
EDUULHU DOOHUJLHV FRPSOH[ LPPXQH G\VUHJXODWLRQ DQG ,J(PHGLDWHG LQIODPPDWRU\ SDWKZD\V
*HQHWLF DVVRFLDWLRQV RI $' KDYH DOVR EHHQ LQGLFDWHG LQFOXGLQJ PXWDWLRQ RI WKH SURILODJJULQ
FLGJHQHUHVSRQVLEOHIRUDNH\VWUXFWXUDOSURWHLQRIWKHXSSHUHSLGHUPDOOD\HURIVNLQ

$YDLODELOLW\DQG(IILFDF\RI$OUHDG\$SSURYHG7KHUDSLHV
7KH-RLQW7DVN)RUFHRQ3UDFWLFH3DUDPHWHUVUHSUHVHQWLQJWKH$PHULFDQ$FDGHP\RI$OOHUJ\
$VWKPD 	 ,PPXQRORJ\ $$$$, WKH $PHULFDQ &ROOHJH RI $OOHUJ\ $VWKPD 	 ,PPXQRORJ\
$&$$,DQGWKH-RLQW&RXQFLORI$OOHUJ\$VWKPDDQG,PPXQRORJ\HVWDEOLVKHGJXLGHOLQHVIRU
$' WKHUDS\ LQ  $FFRUGLQJ WR WKHVH JXLGHOLQHV WKH ILUVW OLQH PDQDJHPHQW RI $' PXVW
LQFOXGHDFRPELQDWLRQRIVNLQK\GUDWLRQWRSLFDOFRUWLFRVWHURLGVFDOFLQHXULQLQKLELWRUVWDFUROLPXV
3URWRSLF(OLGHORYHUWKHFRXQWHU27&WDUSUHSDUDWLRQVDQWLKLVWDPLQHV9LWDPLQ'RUGLOXWH
EOHDFKEDWKV7RSLFDOFRUWLFRVWHURLGVFUHDPVJHOVHPXOVLRQVORWLRQVUHPDLQWKHILUVWFKRLFHRI
WKHUDS\ IRU PDQDJHPHQW RI PLOGVHYHUH IRUPV RI $' $QWLPLFURELDOV RUDO  WRSLFDO DUH
UHFRPPHQGHG WR WUHDW VHFRQGDU\ LQIHFWLRQV LQ $' ,PPXQRPRGXODWLQJ DJHQWV VXFK DV


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



F\FORVSRULQHP\FRSKHQRODWHPRIHWLOD]DWKLRSULQH,)1JDQGFRUWLFRVWHURLGVKDYHEHHQVKRZQ
WRSURYLGHEHQHILWIRUSDWLHQWVZLWKVHYHUHUHIUDFWRU\$'KRZHYHUPDQ\RIWKHPDUHDVVRFLDWHG
SRWHQWLDOVHULRXVDGYHUVHHIIHFWV
$ QHZ IRUPXODWLRQ RI GHVR[LPHWDVRQH ± 'HVR[LPHWDVRQH WRSLFDO VSUD\  KDV EHHQ
GHYHORSHGE\7DUR3KDUPDFHXWLFDOV86$,QFDQGLVWKH7HVWSURGXFWXVHGLQWKLVVWXG\

6FLHQWLILFDQG6WDWLVWLFDO&RQVLGHUDWLRQV
,QVRPHLQVWDQFHVKLJKSRWHQF\VWHURLGVDSSOLHGWRSLFDOO\KDYHEHHQNQRZQWRFDXVHVXSSUHVVLRQ
RIWKHK\SRWKDODPLFSLWXLWDU\DGUHQDO+3$D[LV,QRUGHUWRDVVHVV+3$D[LVIXQFWLRQSODVPD
OHYHOVRIFRUWLVRODUHPHDVXUHGEHIRUHEDVDODQGDIWHUDEROXVDGPLQLVWUDWLRQRIV\QWKHWLFĮ
DGUHQRFRUWLFRWURSLFKRUPRQH$&7+,QWKLVVWXG\&RUWURV\Q70FRV\QWURSLQDV\QWKHWLF
VXEXQLW RI $&7+ $PSKVWDU 3KDUPDFHXWLFDOV ,QF ZLOO EH XVHG DFFRUGLQJ WR PDQXIDFWXUHU
LQVWUXFWLRQVWRDVVHVV+3$D[LVIXQFWLRQ6HH$SSHQGLFHV()5HFRYHU\IURPVWHURLGLQGXFHG
DGUHQDO LQVXIILFLHQF\ LV XVXDOO\ UDSLG DIWHU WKH WUHDWPHQW LV ZLWKGUDZQ 6HH $SSHQGL[ ( IRU
IXUWKHU H[SODQDWLRQ RI WKH HYDOXDWLRQ RI WKH UROH RI WRSLFDO FRUWLFRVWHURLGV LQ +3$ D[LV
VXSSUHVVLRQ
7DUR 3KDUPDFHXWLFDOV 86$ KDV UHFHQWO\ FRPSOHWHG DQ RSHQ ODEHO VDIHW\ DQG HIILFDF\ VWXG\ WR
DVVHVVDGUHQDOVXSSUHVVLRQLQDGXOWVZLWKPRGHUDWHWRVHYHUHSODTXHSVRULDVLVDIWHUZHHNVRI
WUHDWPHQWXQGHUPD[LPDOXVHFRQGLWLRQVZLWKWKHWHVWSURGXFWGHVR[LPHWDVRQHVSUD\2I
HYDOXDEOHVXEMHFWVDGUHQDOVXSSUHVVLRQZDVLGHQWLILHGLQRIVXEMHFWVKDYLQJLQYROYHPHQW
RIRIERG\VXUIDFHDUHD%6$DQGRIVXEMHFWVKDYLQJLQYROYHPHQWRI!RI%6$
DIWHUWUHDWPHQWZLWK7RSLFRUW7RSLFDO6SUD\WZLFHDGD\IRUGD\V$GUHQDOIXQFWLRQUHWXUQHG
WRQRUPDODWWKHILUVWIROORZXSYLVLWZKLFKZDVGD\VDIWHUWKHHQGRIWUHDWPHQWIRUDOORI
WKHVHSDWLHQWV
7KLVVWXG\GHVLJQLVEDVHGRQVLPLODUVWXGLHVSHUIRUPHGVXEPLWWHGDQGDFFHSWHGE\WKH)'$IRU
UHFHQWO\ DSSURYHG KLJK SRWHQF\ VSUD\ DQG IRDP WRSLFDO FRUWLFRVWHURLG IRUPXODWLRQV WRSLFDO
FRUWLFRVWHURLGWRSLFDOYLWDPLQ'DQDORJXHFRPELQDWLRQDJHQWVDQGUHFRPPHQGDWLRQVIURPWKH
)'$LQ,1'*XLGDQFH0HHWLQJWKDWWRRNSODFHRQDQGDQ)'$$GYLFH/HWWHU
GDWHG

5LVNVDQG%HQHILWV
.QRZQDGYHUVHUHDFWLRQVWRWRSLFDOFRUWLFRVWHURLGVLQFOXGHEXUQLQJLWFKLQJLUULWDWLRQGU\QHVV
IROOLFXOLWLVK\SHUWULFKRVLVDFQHLIRUPHUXSWLRQVK\SRSLJPHQWDWLRQSHULRUDOGHUPDWLWLVDOOHUJLF
FRQWDFW GHUPDWLWLV PDFHUDWLRQ RI WKH VNLQ VHFRQGDU\ LQIHFWLRQ VNLQ DWURSK\ VWULDH DQG
PLOOLDULD'RVLQJIRUH[WHQGHGSHULRGVRIWLPHPD\UHVXOWLQVXSSUHVVLRQRIDGUHQDOIXQFWLRQ
&RUWURV\Q70IRULQMHFWLRQLVLQWHQGHGGLDJQRVWLFDQGQRWWKHUDSHXWLFXVHDQGDGYHUVHUHDFWLRQV
RWKHU WKDQ D UDUH K\SHUVHQVLWLYLW\ UHDFWLRQ DUH QRW DQWLFLSDWHG  .QRZQ UHDFWLRQV DUH VOLJKW
ZKHDOLQJZLWKHU\WKHPDDWWKHVLWHRILQMHFWLRQ
7KHVXEMHFWPD\EHQHILWIURPFOHDULQJRIWKHOHVLRQVDQGLPSURYHPHQWRIWKHFRQGLWLRQRIWKH
GLVHDVH,IWKHGUXJLVDSSURYHGWKHQPDQ\FKLOGUHQPD\EHQHILWIURPLWVXVH


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



7KH SRWHQWLDO ULVNV DQG EHQHILWV RI SDUWLFLSDWLRQ LQ WKH VWXG\ ZLOO EH H[SODLQHGWRWKHSDWLHQW
DQGSDUHQWRUOHJDOJXDUGLDQYHUEDOO\DQGZULWWHQLQWKHLQIRUPHGFRQVHQWIRUP
$OO SDWLHQWV HQUROOHG LQ WKLV VWXG\ ZLOO UHFHLYH WKH EHQHILW RI IUHH VSHFLDOL]HG PHGLFDO FDUH
EH\RQGVWDQGDUGPHGLFDOWUHDWPHQWWKDWZRXOGEHH[SHFWHGWKURXJKPRVWKHDOWKLQVXUDQFHSODQV
,Q DGGLWLRQ WKH SDWLHQW ZLOO UHFHLYH D VWLSHQG DV FRPSHQVDWLRQ IRU WLPH DQG LQFRQYHQLHQFH
UHODWHGWRVWXG\SDUWLFLSDWLRQLQFOXGLQJFRVWVDVVRFLDWHGZLWKWUDYHOWRDQGIURPWKHPHGLFDO
IDFLOLW\
(WKLFDOFRQVLGHUDWLRQUHODWHGWRWKLVSURWRFRODQGWKHXVHRIKXPDQSDWLHQWVZLOOEHUHYLHZHGE\
DQ,5%

 678'<2%-(&7,9(6
 7KHSULPDU\REMHFWLYHRIWKLVVWXG\LVWRHYDOXDWHWKHSRWHQWLDORIGHVR[LPHWDVRQHWRSLFDO
VSUD\WRVXSSUHVV+3$D[LVIXQFWLRQLQSDWLHQWVZLWKPRGHUDWHWRVHYHUHDWRSLFGHUPDWLWLV
 7KHVHFRQGDU\REMHFWLYHVDUHWRHYDOXDWHWKHHIILFDF\SDUDPHWHUVDQGDGYHUVHHYHQW$(SURILOH
RIGHVR[LPHWDVRQHWRSLFDOVSUD\DGPLQLVWHUHGWRSDWLHQWVZLWKPRGHUDWHWRVHYHUHDWRSLF
GHUPDWLWLV


,19(67,*$7,21$/3/$1

6WXG\'HVLJQDQG3ODQ'HVFULSWLRQ
7KLVRSHQODEHOVDIHW\VWXG\LVGHVLJQHGWRHYDOXDWHWKHSRWHQWLDOIRUDGUHQDOVXSSUHVVLRQDIWHU
WUHDWPHQW ZLWK GHVR[LPHWDVRQH  WRSLFDO VSUD\ 7DUR 3KDUPDFHXWLFDOV 86$ IRU WKH
WUHDWPHQWRIPRGHUDWHWRVHYHUHDWRSLFGHUPDWLWLV
$SSUR[LPDWHO\WRHOLJLEOHSDWLHQWVZLWKDWRSLFGHUPDWLWLVWKDWVDWLVI\DOOHOLJLELOLW\FULWHULD
ZLOOEHHQUROOHGLQWRWKHVWXG\DW9LVLW3DWLHQWVPXVWEHRYHUDOOLQJRRGKHDOWK7KH\VKRXOG
KDYHDFXUUHQWGLDJQRVLVRIPRGHUDWHWRVHYHUHDWRSLFGHUPDWLWLVZLWK,*$VFRUHRIDWOHDVWRU
$SSUR[LPDWHO\WZHQW\ILYHWRILIW\SDWLHQWVVWUDWLILHGE\DJHZLWKDFRQILUPHGGLDJQRVLV
RIPRGHUDWHWRVHYHUHDWRSLFGHUPDWLWLVZLWK
&RKRUW±SDWLHQWVDJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
&RKRUW±SDWLHQWVDJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
&RKRUW±SDWLHQWVDJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
&RKRUW±SDWLHQWVPRQWKVWR\HDURIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG

&RKRUWVZLOOEHHQUROOHGLQVHTXHQWLDORUGHU(DFKFRKRUWZLOOLQLWLDWHHQUROOPHQWRQFHWKH
SUHYLRXVFRKRUWKDVUHDFKHGWKHPLQLPXPQXPEHURISDWLHQWVDQGDVDIHW\DQDO\VLVKDVEHHQ
UHYLHZHG(DFKFRKRUWZLOOEHHQUROOHGEDVHGRQWKHDYDLODELOLW\RISDWLHQWV

(DFKFRKRUWZLOOEHUHYLHZHGIRUWKHSRWHQWLDORI+3$D[LVVXSSUHVVLRQ,IDWOHDVWRISDWLHQWV
LQD&RKRUWH[SHULHQFH+3$D[LVVXSSUHVVLRQHQUROOPHQWIRUWKDWFRKRUWZLOOEHVWRSSHGDQGQR
IXUWKHUFRKRUWVZLOOEHLQLWLDWHG,IDWOHDVWRISDWLHQWVKDYHH[SHULHQFHG+3$D[LV
VXSSUHVVLRQDFURVVDOOFRKRUWVFRPELQHGGXULQJWKHVWXG\HQUROOPHQWZLOOEHGLVFRQWLQXHGDQGQR


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



RWKHUFRKRUWVZLOOEHLQLWLDWHG&RKRUWZLOOQRWEHJLQXQWLOVDIHW\GDWDKDVEHHQUHYLHZHGIRU
&RKRUW7KHVDPHSURFHVVZLOOEHIROORZHGIRUHDFK&RKRUWXQWLOWKHVWXG\LVFRPSOHWH
7KHHQUROOPHQWLQWKHLQGLYLGXDO&RKRUWPD\QRWEHUHTXLUHGLIWKHVDWLVIDFWRU\VDIHW\GDWDIRUWKH
VDPHDJHJURXSZDVREWDLQHGLQWKHVWXG\'6;6

3DWLHQWVHQUROOHGLQWKHVWXG\ZLOODSSO\SURGXFWWZLFHDGD\DFFRUGLQJWRSURYLGHGLQVWUXFWLRQV
IRUDWRWDORIGD\V
3DWLHQWVZLOODWWHQGDWRWDORI&OLQLF9LVLWVDVIROORZV
·
9LVLW'D\6FUHHQLQJ(QUROOPHQW
·
9LVLW'D\,QWHULP9LVLW
·
9LVLW'D\(QGRI6WXG\RU(DUO\7HUPLQDWLRQ
7KH SULPDU\ HQGSRLQW LV WKH SURSRUWLRQ RI SDWLHQWV LQ WKH VWXG\ ZLWK +3$ D[LV VXSSUHVVLRQ
IROORZLQJWUHDWPHQWZLWKWKHVWXG\PHGLFDWLRQ
7KHVDIHW\SURILOHRIHDFKWUHDWPHQWJURXSZLOOEHHYDOXDWHGE\FRPSDULQJDGYHUVHHYHQWV
(WKLFDOFRQVLGHUDWLRQUHODWHGWRWKLVSURWRFRODQGWKHXVHRIKXPDQSDWLHQWVZLOOEHUHYLHZHGE\DQ
,5%

6HOHFWLRQRI6WXG\'HVLJQ
7KLVRSHQODEHOVDIHW\VWXG\WRDVVHVVWKHSRWHQWLDORIGHVR[LPHWDVRQHWRSLFDOVSUD\WR
VXSSUHVV+3$D[LVIXQFWLRQZDVEDVHGRQUHFRPPHQGDWLRQVSURYLGHGE\WKH)'$LQ,1'
*XLGDQFH0HHWLQJ5HIHUHQFH,'UHJDUGLQJWKHVFRSHDQGGHVLJQRI
VWXGLHVIRUGHVR[LPHWDVRQHVSUD\DQGDQ)'$$GYLFH/HWWHUGDWHG

6HOHFWLRQRI6WXG\3RSXODWLRQ

,QFOXVLRQ&ULWHULD
 0DOHRUQRQSUHJQDQWQRQODFWDWLQJIHPDOHV
·
&RKRUW±DJHV\HDUVRIDJH
·
&RKRUW±DJHV\HDUVRIDJH
·
&RKRUW±DJHV\HDUVRIDJH
·
&RKRUW±PRQWKV\HDURIDJH
 ,I IHPDOH DQG RI FKLOGEHDULQJ SRWHQWLDO SUHSDUHG WR DEVWDLQ IURP VH[XDO LQWHUFRXUVH RU XVH D
UHOLDEOH PHWKRG RI FRQWUDFHSWLRQ GXULQJ WKH VWXG\ HJ FRQGRP ,8' RUDO WUDQVGHUPDO RU
LQMHFWHGKRUPRQDOFRQWUDFHSWLYHV
 3DUHQWOHJDOJXDUGLDQKDVVLJQHGLQIRUPHGFRQVHQWIRUPZKLFKPHHWVDOOFULWHULDRIFXUUHQW)'$
UHJXODWLRQV
 %DVHG RQ WKH SDWLHQW¶V DJH   \HDUV ROG ZLOO UHDG DQG VLJQ DQ ,5% DSSURYHG DVVHQW IRUP
3DWLHQWV\HDUVRIDJHZLOOSURYLGHYHUEDODVVHQWWRSDUWLFLSDWH
 3DWLHQWVZLWKDGHILQLWHFOLQLFDOGLDJQRVLVRIVWDEOHDWRSLFGHUPDWLWLVZLWKLQYROYHPHQWRI
·
&RKRUW±DJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
H[FOXGLQJIDFHD[LOODDQGJURLQDUHDV


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



·
&RKRUW±DJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
H[FOXGLQJIDFHD[LOODDQGJURLQDUHDV
·
&RKRUW±DJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
H[FOXGLQJIDFHD[LOODDQGJURLQDUHDV
·
&RKRUW±PRQWKV±\HDURIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
H[FOXGLQJIDFHD[LOODDQGJURLQDUHDV
 +DYHDQ(F]HPD$UHDDQG6HYHULW\,QGH[($6,VFRUHRIDWOHDVW
 +DYHDQ,QYHVWLJDWRU*OREDO$VVHVVPHQW6FDOH,*$RI0RGHUDWHRU6HYHUH

([FOXVLRQ&ULWHULD
 )HPDOHV ZKR DUH SUHJQDQW QXUVLQJ SODQQLQJ WR EHFRPH SUHJQDQW GXULQJ WKH GXUDWLRQ RI WKH
VWXG\ RU LI RI FKLOGEHDULQJ SRWHQWLDO DQG VH[XDOO\ DFWLYH DQG QRW SUHSDUHG WRXVH DSSURSULDWH
FRQWUDFHSWLYHPHWKRGVWRDYRLGSUHJQDQF\
 /DFNVVWDEOHGLDJQRVLVRIDWRSLFGHUPDWLWLVRUKDVEHHQGLDJQRVHGZLWKPLOGDWRSLFGHUPDWLWLV
 +DYHDQ($6,VFRUHRI
 +DYHDQ,*$VFRUHRI
 $WRSLFGHUPDWLWLVZLWKD%6$LQYROYHPHQWRIRU!
 $FWLYH FXWDQHRXV EDFWHULDO RU YLUDO LQIHFWLRQ LQ DQ\ WUHDWPHQW DUHD DW EDVHOLQH LH FOLQLFDOO\
LQIHFWHGDWRSLFGHUPDWLWLV
 3DWLHQW KDV D KLVWRU\ RI DWRSLF GHUPDWLWLV WKDW KDV EHHQ XQUHVSRQVLYH WR WRSLFDO FRUWLFRVWHURLG
WKHUDS\
 $Q\FRQGLWLRQLHVXQEXUQSVRULDVLVHWFWKDWLQWKH,QYHVWLJDWRU¶VRSLQLRQPD\LQWHUIHUHZLWK
WKHFOLQLFDODVVHVVPHQWVRIWKHVLJQVDQGV\PSWRPVRIDWRSLFGHUPDWLWLV
 3DWLHQW KDV D KLVWRU\ RI DOOHUJ\ RU VHQVLWLYLW\ WR FRUWLFRVWHURLGV RU KLVWRU\ RI DQ\ GUXJ
K\SHUVHQVLWLYLW\RULQWROHUDQFHZKLFKLQWKHRSLQLRQRIWKH,QYHVWLJDWRUZRXOGFRPSURPLVHWKH
VDIHW\RIWKHSDWLHQWRUWKHUHVXOWVRIWKHVWXG\
3DWLHQWKDVDVLJQLILFDQWKLVWRU\RUFXUUHQWHYLGHQFHRIFKURQLFLQIHFWLRXVGLVHDVHV\VWHPGLVRUGHU
RUJDQ GLVRUGHU RU RWKHU PHGLFDO FRQGLWLRQ WKDW LQ WKH ,QYHVWLJDWRU¶V RSLQLRQ ZRXOG SODFH WKH
VWXG\SDWLHQWDWXQGXHULVNE\SDUWLFLSDWLRQLQWKHVWXG\
3DWLHQW LV FXUUHQWO\ UHFHLYLQJ RU KDV UHFHLYHG DQ\ UDGLDWLRQ WKHUDS\ DQWLQHRSODVWLF DJHQWV RU
LPPXQRVXSSUHVVDQWPHGLFDWLRQZLWKLQZHHNVEHIRUHWKHILUVWGRVHRIVWXG\GUXJ
8VHZLWKLQRQHPRQWK EHIRUHEDVHOLQHRIRUDORULQWUDYHQRXVFRUWLFRVWHURLGV89$89%
WKHUDS\389$SVRUDOHQSOXVXOWUDYLROHW$WKHUDS\WDQQLQJERRWKVQRQSUHVFULSWLRQ89
OLJKWVRXUFHLPPXQRPRGXODWRUVRULPPXQRVXSSUHVVLYHWKHUDSLHVLQWHUIHURQF\WRWR[LF
GUXJVWDFUROLPXVRUSLPHFUROLPXV
8VHZLWKLQGD\VEHIRUHEDVHOLQHRIV\VWHPLFDQWLELRWLFVFDOFLSRWULHQHRURWKHU9LWDPLQ'
SUHSDUDWLRQVRUUHWLQRLGV
3DWLHQWVZKRKDYHXVHGWRSLFDOWUHDWPHQWVSUHVFULSWLRQRURYHUWKHFRXQWHULQFOXGLQJ
D $Q\ WRSLFDO DWRSLF GHUPDWLWLV WKHUDSHXWLF DJHQWV RI DQ\ NLQG ZLWKLQ WKH  ZHHNV
EHIRUHILUVWXVHRIVWXG\GUXJ
E $Q\WRSLFDOFRUWLFRVWHURLGVZLWKLQWKHZHHNVEHIRUHWKHILUVWXVHRIWKHVWXG\GUXJ
F $Q\DQWLEDFWHULDOPHGLFDWHGDQGRUDVWULQJHQWZDVKHVVRDSVSDGVRUPRLVWXUL]HUV
ZLWKLQWKHGD\VEHIRUHWKHILUVWXVHRIVWXG\GUXJ
G +LJK VWUHQJWK  RU DERYH DOSKDK\GUR[\ DFLG RU DQ\ NLQG RI SHHO RU RWKHU
SURFHGXUHVRQWKHIDFHHJODVHUKDLUUHPRYDOZLWKLQGD\VRIWKHVWXG\VWDUW


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



H $Q\WRSLFDOSURGXFWVLHVXQVFUHHQVORWLRQVFUHDPVH[FHSWIRUEODQGHPROOLHQW
PRLVWXUL]HUZLWKLQKRXUEHIRUHEDVHOLQH
I 7RSLFDODQWLELRWLFVLQWKHWUHDWPHQWDUHDZLWKLQGD\VEHIRUHEDVHOLQH
3DWLHQWKDVEHHQWUHDWHGZLWKLQZHHNVRUILYHKDOIOLYHVZKLFKHYHULVOHVVEHIRUHWKHILUVW
GRVHRIVWXG\GUXJZLWKDQ\ELRORJLFDOWKHUDSLHVIRUDWRSLFGHUPDWLWLV
8VHRIQRQVHGDWLQJDQWLKLVWDPLQHVZLWKLQWKHGD\VEHIRUHWKHILUVWGRVLQJGD\
7KHXVHRIVHGDWLQJDQWLKLVWDPLQHVVXFKDVGLSKHQK\GUDPLQHPD\EHDFFHSWDEOHRQFRQGLWLRQ
WKHSDWLHQWKDVEHHQRQDVWDEOHGRVHIRUDWOHDVWGD\VEHIRUHWKHVWXG\VWDUWDQGZLOOUHPDLQRQ
DVWDEOHGRVHWKURXJKRXWWKHVWXG\
$Q\RUDOVWHURLGGUXJXVHZLWKWKHH[FHSWLRQFRQWUDFHSWLYHVZLWKLQGD\VRIWKHILUVWGRVLQJ
GD\RUGXULQJWKHVWXG\
D )HPDOH SDWLHQWV XVLQJ KRUPRQDO FRQWUDFHSWLYHV VKRXOG KDYH EHHQ RQ WKH VDPH
SURGXFWGRVLQJ UHJLPHQ IRU DW OHDVW  GD\V EHIRUH DQG VKRXOG QRW FKDQJH WKLV
UHJLPHQGXULQJWKHVWXG\
E 7KHXVHRILQKDOHGRULQWUDQDVDOFRUWLFRVWHURLGVLVDFFHSWDEOHDVORQJDVXVDJHKDV
EHHQ VWDEOH IRU DW OHDVW  ZHHNV EHIRUH WKH ILUVW GRVH RI VWXG\ GUXJ DQG ZLOO EH
FRQWLQXHGGXULQJWKHVWXG\
,QDELOLW\WRXQGHUVWDQGWKHSURWRFROUHTXLUHPHQWVLQVWUXFWLRQVDQGVWXG\UHODWHGUHVWULFWLRQVWKH
QDWXUHVFRSHDQGSRVVLEOHFRQVHTXHQFHVRIWKHFOLQLFDOVWXG\
8QOLNHO\WRFRPSO\ZLWKWKHSURWRFROUHTXLUHPHQWVLQVWUXFWLRQVDQGVWXG\UHODWHGUHVWULFWLRQV
VXFK DV XQFRRSHUDWLYH DWWLWXGH LQDELOLW\ WR UHWXUQ IRU IROORZXS YLVLWV DQG LPSUREDELOLW\ RI
FRPSOHWLQJWKHFOLQLFDOVWXG\
5HFHLSWRIDQ\GUXJDVSDUWRIDUHVHDUFKVWXG\ZLWKLQGD\VSULRUWRILUVWGRVLQJ
7KH SDWLHQW LV D PHPEHU RI WKH LQYHVWLJDWLRQDO VWXG\ VWDII RU D PHPEHU RI WKH IDPLO\ RI WKH
LQYHVWLJDWLRQDOVWXG\VWDII
3UHYLRXVSDUWLFLSDWLRQLQWKLVVWXG\LQFOXGLQJSDWLHQWVSUHYLRXVO\HQUROOHGLQ'6;6

5HVWULFWLRQVGXULQJWKH6WXG\
7KHIROORZLQJFRQFRPLWDQWPHGLFDWLRQVZLOOQRWEHDOORZHGZKLOHHQUROOHGLQWKHVWXG\
·
$Q\SUHVFULSWLRQRURYHUWKHFRXQWHU27&WRSLFDOV\VWHPLFSKRWRWKHUDS\RUELRORJLFDO
PHGLFDWLRQVRUWUHDWPHQWVIRU$'
·
$Q\QRQVWHURLGDOLPPXQRVXSSUHVVDQWVE\DQ\URXWHRIDGPLQLVWUDWLRQ
·
8VHRIQRQVHGDWLQJDQWLKLVWDPLQHV
o 7KH XVH RI VHGDWLQJ DQWLKLVWDPLQHV VXFK DV GLSKHQK\GUDPLQH PD\ EH DFFHSWDEOH RQ
FRQGLWLRQWKHSDWLHQWKDVEHHQRQDVWDEOHGRVHIRUDWOHDVWGD\VEHIRUHHQUROOPHQWDQG
ZLOOUHPDLQRQDVWDEOHGRVHWKURXJKRXWWKHVWXG\
·
$Q\ RUDO WRSLFDO RU LQMHFWDEOH VWHURLG GUXJ XVH ZLWK WKH H[FHSWLRQ RI +57 DQG
FRQWUDFHSWLYHV


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



o )HPDOHSDWLHQWVXVLQJKRUPRQDOFRQWUDFHSWLYHVRU+57VKRXOGKDYHEHHQRQWKHVDPH
SURGXFWGRVLQJUHJLPHQIRUDWOHDVWZHHNVEHIRUHDQGVKRXOGQRWFKDQJHWKLVGXULQJWKH
VWXG\
·
1HZUHJLPHQVRILQKDOHGFRUWLFRVWHURLGV
o ,QKDOHGRULQWUDQDVDOFRUWLFRVWHURLGVDUHSHUPLVVLEOHSURYLGHGWKDWWKHSDWLHQWKDVEHHQRQ
DVWDEOHUHJLPHQIRUDWOHDVWZHHNVEHIRUHWKHILUVWGRVHRIVWXG\GUXJDQGZLOOFRQWLQXH
GXULQJWKHVWXG\
·
$Q\RWKHUWUHDWPHQWVSUHVFULSWLRQRURYHUWKHFRXQWHUSURGXFWVIRUWKHWUHDWPHQWRIDQ\
RWKHUGHUPDWRORJLFDOFRQGLWLRQLQFOXGLQJWRSLFDOFRUWLFRVWHURLGVDQWLEDFWHULDOPHGLFDWHG
DQGRUDVWULQJHQWZDVKHVVRDSVSDGVRUPRLVWXUL]HUVGXULQJWKHVWXG\
·
8VHRIKLJKVWUHQJWKRUDERYHDOSKDK\GUR[\ DFLGRUDQ\NLQGRISHHORURWKHU
SURFHGXUHVRQWKHWUHDWPHQWDUHDVODVHUKDLUUHPRYDOGXULQJWKHVWXG\
3DWLHQWV DQG SDUHQWVOHJDO JXDUGLDQV ZLOO EH DGYLVHG WR DYRLG HQYLURQPHQWDO FRQGLWLRQV WKDW PD\
H[DFHUEDWHWKHLUGLVHDVHVWDWH3DWLHQWVDQGSDUHQWVOHJDOJXDUGLDQVZLOOEHDGYLVHGWRDYRLGH[SRVXUH
WRVXQOLJKWRIDGXUDWLRQWKDWZRXOGUHTXLUHDSSOLFDWLRQRIVXQVFUHHQ
3DWLHQWVDQGSDUHQWVOHJDOJXDUGLDQVZLOOEHLQVWUXFWHGQRWWRDSSO\WKHPHGLFDWLRQWRWKHIDFHJURLQRU
D[LOODDQGQRWWRXVHRFFOXVLYHGUHVVLQJVRQWKHWUHDWPHQWDUHD
3DWLHQWVDQGSDUHQWVOHJDOJXDUGLDQVZLOOEHTXHVWLRQHGDERXWDOOFRQFRPLWDQWSUHVFULSWLRQDQG27&
PHGLFDWLRQXVHDWHDFKVWXG\YLVLW$OOFRQFRPLWDQWPHGLFDWLRQVZLOOEHUHFRUGHGLQWKHSDWLHQW¶VVWXG\
FKDUW $Q\ SDWLHQW ZKR YLRODWHV DQ\ RI WKH OLVWHG UHVWULFWLRQV PD\ EH GURSSHG IURP FRQWLQXHG
SDUWLFLSDWLRQLQWKHVWXG\E\WKH,QYHVWLJDWRU

5HPRYDORI3DWLHQWVIURPWKH6WXG\
3DWLHQWVDQGSDUHQWVOHJDOJXDUGLDQVZLOOEHDGYLVHGWKDWWKH\DUHIUHHWRZLWKGUDZIURPWKHVWXG\DW
DQ\WLPHIRUDQ\UHDVRQRULIQHFHVVDU\WKH,QYHVWLJDWRUPD\ZLWKGUDZDSDWLHQWIURPWKHVWXG\WR
SURWHFWWKH KHDOWK RIWKDW SDWLHQW $ SDWLHQW PD\ DOVR EH ZLWKGUDZQIRU QRW FRPSO\LQJ ZLWK VWXG\
SURFHGXUHV7KHFOLQLFDOUHSRUWZLOOLQFOXGHDOOUHDVRQVIRUHDUO\ZLWKGUDZDOV
$OOSDWLHQWVZKRDGPLQLVWHUDWOHDVWRQHGRVHRIUDQGRPL]HGVWXG\PHGLFDWLRQZLOOEHLQFOXGHGLQWKH
VDIHW\DQDO\VLV,IDSDWLHQWWHUPLQDWHVIURPWKHVWXG\HDUO\DOOHIIRUWVZLOOEHPDGHWRFRPSOHWHWKHLU
QH[W YLVLW VWXG\ SURFHGXUHV ,Q FDVH RI HDUO\ WHUPLQDWLRQ WKH ,QYHVWLJDWRU VKDOO IXOO\ GRFXPHQW WKH
UHDVRQIRUHDUO\WHUPLQDWLRQ5HDVRQVIRUHDUO\WHUPLQDWLRQPD\LQFOXGHWKHIROORZLQJ
·
3DWLHQWZLWKGUHZFRQVHQW
·
6LJQLILFDQW DGYHUVH HYHQW WKDW OHG WKH ,QYHVWLJDWRU RU SDWLHQW WR ZLWKGUDZ IRU VDIHW\
UHDVRQV
·
:RUVHQLQJVLJQVV\PSWRPVRI$'
·
'HYHORSPHQWRIDQLQWHUFXUUHQWFRQGLWLRQRUFRPSOLFDWLRQWKDWFRXOGDIIHFWWKHVDIHW\RI
WKH SDWLHQW RU WKH YDOLGLW\ RI WKH HYDOXDWLRQ RI WKH SDWLHQW¶V FOLQLFDO VWDWH WR DQ H[WHQW
FRQVLGHUHGVLJQLILFDQWE\WKH,QYHVWLJDWRU


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



·
6LJQVDQGV\PSWRPVRISRVVLEOH+3$D[LVVXSSUHVVLRQ
·
3URWRFROGHYLDWLRQVYLRODWLRQVWKDWLQWKH,QYHVWLJDWRU¶VRSLQLRQZDUUDQWGLVFRQWLQXDWLRQ
1RQFRPSOLDQFHZLWKGRVLQJQHHGQRWEHDUHDVRQIRUHDUO\WHUPLQDWLRQ3DWLHQWVZKRZLWKGUDZRUDUH
UHPRYHGIURPWKHVWXG\ZLOOQRWEHUHSODFHG,QWKHHYHQWDSDWLHQWZLWKGUDZVRULVGURSSHGIURPWKH
VWXG\IRUDQ\UHDVRQWKH,QYHVWLJDWRUZLOOUHTXHVWUHWXUQRIWKHXQXVHGSURGXFWDQGUHSRUWWKHUHDVRQ
IRUWKHGLVFRQWLQXHGSDUWLFLSDWLRQ
:KHQDSDWLHQWGLVFRQWLQXHVHDUO\IURPWKHVWXG\DOOVWXG\SURFHGXUHVUHTXLUHGIRUWKHHQGRIVWXG\
VKRXOG EH SHUIRUPHG DW WKHLU ODVW VWXG\ YLVLW 3DWLHQWV ZKR DUH GLVFRQWLQXHG IURP WKH VWXG\ DIWHU
HQUROOPHQWZLOOEHHYDOXDWHGIRUVDIHW\DQGZLOOEHJLYHQRUUHIHUUHGIRUDSSURSULDWHWUHDWPHQW

7UHDWPHQWV

7UHDWPHQWV$GPLQLVWUDWLRQ
7KHSDWLHQWRUSDUHQWOHJDOJXDUGLDQZLOOEHLQVWUXFWHGWRDSSO\DQGUXELQJHQWO\DWKLQILOPRIWKH
VWXG\GUXJWRWKHDIIHFWHGDUHDVWZLFHGDLO\PRUQLQJDQGHYHQLQJIRUGD\V7KHKDQGVVKRXOGEH
ZDVKHGDIWHUDSSO\LQJWKHGUXJ
7R HQVXUH FRPSOLDQFH ZLWK WKH GRVLQJ WHFKQLTXH WKH SDWLHQW RU SDUHQWOHJDO JXDUGLDQ ZLOO EH
LQVWUXFWHGWRDSSO\WKHILUVWGRVHRIPHGLFDWLRQXQGHUVWDIIVXSHUYLVLRQDWWKHWLPHRIHQUROOPHQWDQG
WKHQWZLFHGDLO\XQWLOWKHSDWLHQW¶VQH[WVFKHGXOHGYLVLW3DWLHQWRUSDUHQWVOHJDOJXDUGLDQVZLOOEH
LQVWUXFWHG QRW WR DSSO\ WKH VWXG\ GUXJ ZLWKLQ  KRXUV RI WKH YLVLW ZKLFK LQFOXGHV WKH &RUWLVRO
5HVSRQVH7HVW7KHSDWLHQWRUSDUHQWOHJDOJXDUGLDQZLOOEHLQVWUXFWHGQRWWRDSSO\WKHPHGLFDWLRQWR
WKHIDFHD[LOODRUJURLQDQGQRWWRXVHRFFOXVLYHGUHVVLQJVRQWKHWUHDWPHQWDUHD (DFKSDWLHQWRU
SDUHQWOHJDOJXDUGLDQZLOOEHSURYLGHGZLWKDGRVLQJGLDU\LQZKLFKWKH\ZLOOEHUHTXLUHGWRUHFRUG
GRVLQJGDWHVDQGWLPHV7KHVHGLDULHVVKRXOGEHEURXJKWWRHDFKYLVLWLQRUGHUWKDWWKHVWXG\VWDIIPD\
FKHFNFRPSOLDQFH$WWKHHQGRIWKHVWXG\WKHGRVLQJGLDULHVZLOOEHUHWDLQHGLQWKHSDWLHQW¶VILOHDV
VRXUFHGRFXPHQWDWLRQ
$W9LVLW6FUHHQLQJ(QUROOPHQWDQG9LVLW,QWHULP9LVLWTXDOLILHGVWXG\SDWLHQWVRUSDUHQWVOHJDO
JXDUGLDQVZLOOEHSURYLGHGZLWKRQHPOERWWOHRIGHVR[LPHWDVRQHWRSLFDOVSUD\DORQJZLWK
LQVWUXFWLRQVIRUGRVLQJ7KLVERWWOHVKRXOGEHZHLJKHGEHIRUHGLVSHQVLQJDQGWKHZHLJKWUHFRUGHG$W
9LVLW,QWHULP9LVLWWKHERWWOHVKRXOGEHFROOHFWHGZHLJKHGDQGWKHZHLJKWUHFRUGHG$QHZ
POERWWOHRIGHVR[LPHWDVRQHWRSLFDOVSUD\VKRXOGEHZHLJKHGDQGWKHZHLJKWUHFRUGHGEHIRUH
GLVSHQVLQJWKHVSUD\ERWWOHDORQJZLWKGRVLQJLQVWUXFWLRQVWRWKHSDWLHQWRUSDUHQWOHJDOJXDUGLDQ7KLV
ERWWOH VKRXOG EH ZHLJKHG DQG WKH ZHLJKW UHFRUGHG XSRQ UHWXUQDW 9LVLW  (QG RI 6WXG\(QG RI
7UHDWPHQW
7UHDWPHQWFRPSOLDQFHZLOOEHHQFRXUDJHGE\LQVWUXFWLQJWKHSDWLHQWRUSDUHQWOHJDOJXDUGLDQRQWKH
SURSHUGRVLQJWHFKQLTXHDQGE\WKHXVHRIWKHGDLO\GLDU\&RPSOLDQFHZLOOEHDVVHVVHGE\HYDOXDWLRQ
RIWKHGLDU\

,GHQWLW\RI,QYHVWLJDWLRQDO3URGXFW
$OOVWXG\GUXJVZLOOEHSURYLGHGE\7DUR3KDUPDFHXWLFDOV86$,QF(DFKSDWLHQWZLOOUHFHLYH[
P/ERWWOHVRIGHVR[LPHWDVRQHWRSLFDOVSUD\


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



7KHVWXG\PHGLFDWLRQZLOOEHVKLSSHGWRHDFK,QYHVWLJDWRU¶VVLWHIURPDFHQWUDOL]HGSKDUPDF\7KH
3ULQFLSDO,QYHVWLJDWRUDWHDFKVLWHLVUHVSRQVLEOHIRUHQVXULQJWKDWDOOVWXG\PHGLFDWLRQVDUHVWRUHGLQD
ORFNHGVHFXUHORFDWLRQZLWKDFFHVVOLPLWHGWRWKH,QYHVWLJDWRUDQGKLVKHUGHVLJQHHV$QDFFXUDWH
LQYHQWRU\RIWKHVWXG\PHGLFDWLRQZLOOEHPDLQWDLQHGLQDFFRUGDQFHZLWKIHGHUDOUHJXODWLRQV
2QFH WKH VLWH KDV EHHQ QRWLILHG WKDW WKH\ PD\ GR VR DOO XQXVHG VWXG\ PHGLFDWLRQ DQG HPSW\ RU
SDUWLDOO\XVHGERWWOHVRIVWXG\PHGLFDWLRQPD\EHUHWXUQHGWRWKH6SRQVRURUGHVLJQHH

0HWKRGRI$VVLJQLQJ3DWLHQWVWR7UHDWPHQW*URXSV
3DWLHQWVHOLJLEOHIRUHQUROOPHQWLQWRWKHVWXG\ZLOOIDOOLQWRRQHRIILYHFRKRUWV
&RKRUW±SDWLHQWVDJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
&RKRUW±SDWLHQWVDJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
&RKRUW±SDWLHQWVDJH\HDUVRIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
&RKRUW±SDWLHQWVPRQWKV\HDURIDJHZLWKERG\VXUIDFHDUHD%6$DIIHFWHG
$W9LVLWHOLJLEOHSDWLHQWVZLOOEHHQUROOHGWRWKHVWXG\DQGDVVLJQHGDSDWLHQWQXPEHU
&RKRUWVZLOOEHHQUROOHGLQVHTXHQWLDORUGHU(DFKFRKRUWZLOOLQLWLDWHHQUROOPHQWRQFHWKHSUHYLRXV
FRKRUWKDVUHDFKHGWKHUHTXLUHGQXPEHURISDWLHQWVDQGDVDIHW\DQDO\VLVKDVEHHQUHYLHZHG(DFK
FRKRUWZLOOEHHQUROOHGEDVHGRQWKHDYDLODELOLW\RISDWLHQWV

(DFKFRKRUWZLOOEHUHYLHZHGIRUWKHSRWHQWLDORI+3$D[LVVXSSUHVVLRQ,IDWOHDVWRISDWLHQWVLQ
HDFK&RKRUWH[SHULHQFH+3$D[LVVXSSUHVVLRQHQUROOPHQWIRUWKDWFRKRUWZLOOEHVWRSSHGDQGQR
IXUWKHUFRKRUWVZLOOEHLQLWLDWHG,IDWOHDVWRISDWLHQWVKDYHH[SHULHQFHG+3$D[LVVXSSUHVVLRQ
DFURVVFRKRUWVFRPELQHGGXULQJWKHVWXG\HQUROOPHQWZLOOEHGLVFRQWLQXHGDQGQRRWKHUFRKRUWVZLOO
EHLQLWLDWHG&RKRUWZLOOQRWEHJLQXQWLOVDIHW\GDWDKDVEHHQUHYLHZHGIRU&RKRUW7KHVDPH
SURFHVVZLOOEHIROORZHGIRUHDFK&RKRUWXQWLOWKHVWXG\LVFRPSOHWH
7KHHQUROOPHQWLQWKHLQGLYLGXDO&RKRUWPD\QRWEHUHTXLUHGLIWKHVDWLVIDFWRU\VDIHW\GDWDIRUWKH
VDPHDJHJURXSZDVREWDLQHGLQWKHVWXG\'6;6

3DFNDJLQJ
7KLVLVDQRSHQODEHOVWXG\7KHVWXG\GUXJZLOOFRQWDLQDODEHOZLWKWKHIROORZLQJLQIRUPDWLRQ
·
3URWRFROQXPEHU
·
%RWWOHQXPEHU
·
6SDFHIRUSDWLHQWQXPEHUSDWLHQW¶VLQLWLDOVDQGGLVSHQVHGGDWH
·
$QRWHWKDWWKHGUXJLVIRU,QYHVWLJDWLRQDO8VH2QO\

$FFRXQWDELOLW\
·
7KH,QYHVWLJDWRURUGHVLJQHHZLOOPDLQWDLQDQLQYHQWRU\RIDOOVWXG\GUXJVXSSOLHVUHFHLYHG
·
7KH,QYHVWLJDWRURUGHVLJQHHZLOOPDLQWDLQDORJRIDOOGUXJGLVSHQVHGWRDQGUHWXUQHGE\WKH
SDWLHQWVDQGQRWHWKHGDWHHDFKGUXJLVUHWXUQHGWRWKH6SRQVRU
·
7KHZHLJKWRIWKHVWXG\GUXJERWWOHVEHIRUHGLVSHQVLQJDQGDIWHUFROOHFWLRQZLOOEHUHFRUGHG
·
$OOVWXG\GUXJZLOOEHVWRUHGDWFRQWUROOHGURRPWHPSHUDWXUHEHWZHHQ&WR&)WR
)H[FXUVLRQVSHUPLWWHGWR&WR&)WR)LQDVHFXUHSODFHZLWKDFFHVVWR
DXWKRUL]HGLQGLYLGXDOVRQO\


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



·
,QWKHHYHQWRIORVVRUDSSDUHQWVSRLODJHRIWKHWHVWSUHSDUDWLRQWKH,QYHVWLJDWRURU
GHVLJQHHPXVWLQIRUPWKHVWXG\PRQLWRU,IQHFHVVDU\DSURSHUO\ODEHOHGUHSODFHPHQWERWWOH
ZLOOEHLVVXHGWRWKHSDWLHQW

&RPSOLDQFH
3DWLHQWVZLOOEHSURYLGHGZLWKDGLDU\ZLWKLQVWUXFWLRQVWRUHFRUGWKHWLPHDQGGDWHRIGRVLQJ
3DWLHQWV ZLOO EH DVNHG WR DOVR UHFRUG DQ\ DGYHUVH HYHQWV DQG FRQFRPLWDQW PHGLFDWLRQV WDNHQ
GXULQJWKHVWXG\
3DWLHQWVZLOOGRVHWZLFHGDLO\IRUGD\V$OOSDWLHQWVZKRDUHHQUROOHGDQGXVHGDWOHDVW
RIVFKHGXOHGGRVHVRIWKHVWXG\GUXJDQGKDYHGDWDIURPDSRVWWUHDWPHQWFRUWLVROUHVSRQVH
WHVWZLOOEHLQFOXGHGLQWKHDQDO\VLV

6WXG\&RQGXFW
7KHFRUWLVROUHVSRQVHWHVWLVWREHGRQHLQWKHPRUQLQJDVWKHERG\¶VSHDNFRUWLVROOHYHOLVGLUHFWO\
UHODWHG WR WKH HYHQW RI DZDNHQLQJ 9LVLW  DQG 9LVLW  VKRXOG EH VFKHGXOHG EHIRUH QRRQ DQG
VXEMHFWVVKRXOGQRWDSSO\WKHVWXG\GUXJZLWKLQKRXUVRI9LVLW

 9LVLW'D\6FUHHQLQJ(QUROOPHQW%HIRUHSP
 ,QIRUPHG &RQVHQW )RU SDWLHQWV XQGHU WKH DJH RI PDMRULW\ LQ WKH VWDWH WKH VWXG\ LV EHLQJ
FRQGXFWHG\HDUVLQPRVWVWDWHVWKHSDUHQWRUOHJDOJXDUGLDQVKRXOGVLJQWKHFRQVHQWIRUPDQG
WKHFKLOGDJH\HDUVROGZLOOEHUHTXLUHGWRVLJQDSDWLHQW³DVVHQW´IRUPWKDWZLOOEHZULWWHQ
LQVXFKDZD\DVWREHXQGHUVWDQGDEOHWRDFKLOG3DWLHQWVDJH\HDUVRIDJHZLOOSURYLGHYHUEDO
DVVHQWWRSDUWLFLSDWH
 0HGLFDO+LVWRU\DQG'HPRJUDSKLFV7KHSDWLHQW¶VGHPRJUDSKLFDQGDFRPSOHWHPHGLFDOKLVWRU\
ZLOOEHREWDLQHGIRUWKHSDWLHQW¶VFXUUHQWDQGSDVWPHGLFDOFRQGLWLRQV
 3K\VLFDO([DPLQDWLRQDQG%6$$VVHVVPHQW$JHQHUDOSK\VLFDOH[DPZLOOEHFRQGXFWHG
7KHSDWLHQW¶VERG\ZHLJKWNJDQGKHLJKWFPZLOODOVREHPHDVXUHGZKLOHWKHSDWLHQWLVOLJKWO\
FORWKHGHJQRFRDWRUVKRHV%6$ZLOOEHDVVHVVHGXVLQJLQVWUXFWLRQVLQ$SSHQGL[$
 9LWDO 6LJQV 7KH SDWLHQW¶V YLWDO VLJQV ZLOO EH WDNHQ DQG UHFRUGHG SXOVH EORRG SUHVVXUH
WHPSHUDWXUHDQGUHVSLUDWLRQUDWH
 3UHJQDQF\7HVW$XULQHSUHJQDQF\WHVWZLOOEHUHTXLUHGRIDOOIHPDOHVRIFKLOGEHDULQJSRWHQWLDO
SULRUWRHQUROOPHQW
 'HUPDWRORJLFDO $VVHVVPHQW  &OLQLFDO VLJQV DQG V\PSWRPV RI $' ZLOO EH HYDOXDWHG E\ WKH
,QYHVWLJDWRUEDVHGRQWKHIROORZLQJ
·
($6,6FRUH$SSHQGL[%
·
,*$6FRUH$SSHQGL[&
·
$SSOLFDWLRQ6LWH5HDFWLRQV$SSHQGL['
 &RQFRPLWDQW0HGLFDWLRQ5HYLHZZLWKWKHSDWLHQWDQGSDUHQWOHJDOJXDUGLDQWKHSDWLHQW¶V
XVHRIFRQFRPLWDQWPHGLFDWLRQZLWKLQWKHODVWZHHNV
 &RQILUP ,QFOXVLRQ([FOXVLRQ 0HW &RQILUP WKH SDWLHQW PHHWV DOO LQFOXVLRQH[FOXVLRQ FULWHULD
SHQGLQJUHVXOWVRIWKH&RUWLVRO5HVSRQVH7HVW


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



 /DERUDWRU\ (YDOXDWLRQV  $ EORRG VDPSOH ZLOO EH FROOHFWHG IRU KHPDWRORJ\ DQG FOLQLFDO
FKHPLVWU\WHVWLQJ6HH$SSHQGL[*
&RUWLVRO5HVSRQVH7HVW$OOSDWLHQWVZLOOKDYHDFRUWLVROUHVSRQVHWHVWSHUIRUPHGDFFRUGLQJWR
WKHSURFHGXUHGHWDLOHGLQ$SSHQGL[(
'LVSHQVH6WXG\GUXJ,ISDWLHQWLVHOLJLEOHWRHQUROOUHFRUGWKHZHLJKWRIRQHERWWOHRIVWXG\GUXJ
DQGGLVSHQVHZLWKLQVWUXFWLRQV
$SSO\6WXG\0HGLFDWLRQ7KHILUVWGRVHRIVWXG\PHGLFDWLRQVKRXOGEHDGPLQLVWHUHGE\WKH
SDWLHQW\HDUVRIDJHRUSDUHQWOHJDOJXDUGLDQDWWKHVLWHXQGHUVWDIIVXSHUYLVLRQ
3URYLGH'RVLQJ'LDU\3URYLGH'LDU\DQGLQVWUXFWSDUHQWOHJDOJXDUGLDQUHJDUGLQJKRZLWLVWREH
ILOOHGRXWDQGKRZVWXG\GUXJLVWREHXVHG
'LVSHQVH6XQVFUHHQ)RUXVHRQO\ZKHQVXQH[SRVXUHFDQQRWEHDYRLGHG
3URYLGH3DWLHQW:ULVWEDQG(DFKSDWLHQWZLOOUHFHLYHDZULVWEDQGWRLQGLFDWHWKDWWKHSDWLHQWLV
XVLQJDPHGLFDWLRQWKDWKDVWKHSRWHQWLDOWRFDXVH+3$D[LVVXSSUHVVLRQ
6FKHGXOH9LVLW

9LVLW'D\,QWHULP9LVLW
  3UHJQDQF\7HVW$SUHJQDQF\WHVWZLOOEHUHTXLUHGRIDOOIHPDOHVRIFKLOGEHDULQJSRWHQWLDO
SULRUWRHQUROOPHQW 
 9LWDO6LJQV7KHSDWLHQW¶VYLWDOVLJQVZLOOEHUHFRUGHGSXOVHEORRGSUHVVXUHWHPSHUDWXUHDQG
UHVSLUDWLRQUDWH 
%6$$VVHVVPHQW%6$FRYHUHGZLWKDWRSLFGHUPDWLWLVZLOOEHDVVHVVHGXVLQJLQVWUXFWLRQVLQ
$SSHQGL[$
.   'HUPDWRORJLFDO $VVHVVPHQW  &OLQLFDO VLJQV DQG V\PSWRPV RI $' ZLOO EH HYDOXDWHG E\ WKH
,QYHVWLJDWRUEDVHGRQWKHIROORZLQJ
·
($6,6FRUH$SSHQGL[%
·
,*$6FRUH$SSHQGL[& 
·
$SSOLFDWLRQ6LWH5HDFWLRQV$SSHQGL['
&RQFRPLWDQW0HGLFDWLRQ5HYLHZZLWKWKHSDWLHQWDQGSDUHQWOHJDOJXDUGLDQWKHSDWLHQW¶VXVH
RIQHZRUFKDQJHLQRQJRLQJFRQFRPLWDQWPHGLFDWLRQVLQFH9LVLW
$GYHUVH(YHQWV3DWLHQWVZLOOEHTXHVWLRQHGDERXWDQ\KHDOWKVWDWXVFKDQJHVDGYHUVHHYHQWVVLQFH
ODVWYLVLW$OOHYHQWVZLOOEHUHFRUGHG
 (YDOXDWLRQRI3DWLHQW&RPSOLDQFHWRWKH3URWRFRO&ROOHFWDQGUHYLHZSDWLHQW¶VGRVLQJGLDU\IRU
FRPSOLDQFH DQG SURYLGH D QHZ GLDU\ 1RQFRPSOLDQFH ZLWK GRVLQJ GRHV QRW ZDUUDQW GLVPLVVDO
IURP WKH VWXG\ &RXQVHO QRQFRPSOLDQW SDWLHQWV DQG SDUHQWVOHJDO JXDUGLDQV RQ GRVLQJ
UHTXLUHPHQWVRIWKHVWXG\
 &ROOHFW6WXG\'UXJ7KHXVHGERWWOHRIVWXG\GUXJZLOOEHFROOHFWHGDQGWKHZHLJKWUHFRUGHG
 'LVSHQVH6WXG\GUXJ,ISDWLHQWFRQWLQXHVLQWKHVWXG\UHFRUGZHLJKWRIRQHERWWOHRIVWXG\
GUXJDQGGLVSHQVH


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



3URYLGH'RVLQJ'LDU\,ISDWLHQWFRQWLQXHVLQWKHVWXG\SURYLGHDQHZGRVLQJGLDU\,QVWUXFW
SDUHQWVOHJDOJXDUGLDQVQRWWRDSSO\GRVHWRSDWLHQWZLWKLQDSSUR[LPDWHO\KRXUVRI9LVLW

9LVLW'D\(QGRI6WXG\RU(DUO\7HUPLQDWLRQ%HIRUHSP
 9LWDO6LJQV7KHSDWLHQW¶VYLWDOVLJQVZLOOEHUHFRUGHGSXOVHEORRGSUHVVXUHWHPSHUDWXUHDQG
UHVSLUDWLRQUDWH
 3UHJQDQF\7HVW$SUHJQDQF\WHVWZLOOEHUHTXLUHGRIDOOIHPDOHVRIFKLOGEHDULQJSRWHQWLDOSULRU
WRHQUROOPHQW
 3K\VLFDO([DP$JHQHUDOSK\VLFDOH[DPZLOOEHFRQGXFWHG
%6$$VVHVVPHQW%6$FRYHUHGZLWKDWRSLFGHUPDWLWLVZLOOEHDVVHVVHGXVLQJLQVWUXFWLRQVLQ
$SSHQGL[$
5.   'HUPDWRORJLFDO $VVHVVPHQW  &OLQLFDO VLJQV DQG V\PSWRPV RI $' ZLOO EH HYDOXDWHG E\ WKH
,QYHVWLJDWRUEDVHGRQWKHIROORZLQJ
·
($6,6FRUH$SSHQGL[%
·
,*$6FRUH$SSHQGL[& 
·
$SSOLFDWLRQ6LWH5HDFWLRQV$SSHQGL['
&RQFRPLWDQW0HGLFDWLRQ5HYLHZZLWKWKHSDWLHQWDQGSDUHQWOHJDOJXDUGLDQWKHSDWLHQW¶VXVH
RIQHZRUFKDQJHLQRQJRLQJFRQFRPLWDQWPHGLFDWLRQVLQFH9LVLW
$GYHUVH(YHQWV3DWLHQWVZLOOEHTXHVWLRQHGDERXWDQ\KHDOWKVWDWXVFKDQJHVDGYHUVHHYHQWVVLQFH
ODVWYLVLW$OOHYHQWVZLOOEHUHFRUGHG
 (YDOXDWLRQRI3DWLHQW&RPSOLDQFHWRWKH3URWRFRO&ROOHFWDQGUHYLHZSDWLHQW¶VGRVLQJGLDU\
IRUFRPSOLDQFH1RQFRPSOLDQFHZLWKGRVLQJGRHVQRWZDUUDQWGLVPLVVDOIURPWKHVWXG\
 &ROOHFW6WXG\'UXJ7KHXVHGERWWOHRIVWXG\GUXJZLOOEHFROOHFWHGDQGWKHZHLJKWUHFRUGHG
/DERUDWRU\ (YDOXDWLRQV  $ EORRG VDPSOH ZLOO EH FROOHFWHG IRU KHPDWRORJ\ DQG FOLQLFDO
FKHPLVWU\WHVWLQJ6HH$SSHQGL[*
&RUWLVRO5HVSRQVH7HVW$OOSDWLHQWVZLOOKDYHDFRUWLVROUHVSRQVHWHVWSHUIRUPHGDFFRUGLQJWR
WKHSURFHGXUHGHWDLOHGLQ$SSHQGL[(
9LVLW'D\)ROORZXS3KRQH&DOO
$ SKRQH FDOO ZLOO EH FRQGXFWHG DSSUR[LPDWHO\  GD\V DIWHU WKH SDWLHQW KDV FRPSOHWHG GRVLQJ WR
IROORZXSRQDQ\QHZDGYHUVHHYHQWVWKDWPD\KDYHRFFXUUHG

6WXG\3URFHGXUHV

,QIRUPHG&RQVHQW
)RUSDWLHQWVXQGHUWKHDJHRIPDMRULW\LQWKHVWDWHWKHVWXG\LVEHLQJFRQGXFWHG\HDUVLQPRVW
VWDWHVWKHSDUHQWRUOHJDOJXDUGLDQVKRXOGVLJQWKHFRQVHQWIRUPDQGIRUSDWLHQWV\HDUVRIDJHRU
ROGHUDQDVVHQWIRUPZLOODOVREHUHTXLUHG)RULOOLWHUDWHSDUHQWVRUOHJDOJXDUGLDQVYHUEDOFRQVHQW
VKRXOGEHREWDLQHGLQWKHSUHVHQFHRIDQGEHFRXQWHUVLJQHGE\DOLWHUDWHZLWQHVV,IDQ\RWKHUODQJXDJH
LVUHTXLUHGWUDQVODWLRQZLOOEHSHUIRUPHGE\DFHUWLILHGWUDQVODWRU7KHFKLOGZLOOEHUHTXLUHGWRVLJQD
SDWLHQW³DVVHQW´IRUPWKDWZLOOEHZULWWHQLQVXFKDZD\DVWREHXQGHUVWDQGDEOHWRDFKLOG3DWLHQWVDJH
\HDUVRIDJHZLOOSURYLGHYHUEDODVVHQWWRSDUWLFLSDWH


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




'HPRJUDSKLFV
$WVFUHHQLQJHDFKSDWLHQWVKDOOEHUHTXLUHGWRSURYLGHEDVLFGHPRJUDSKLFLQIRUPDWLRQGDWHRIELUWK
JHQGHUHWKQLFLW\DQGUDFH

0HGLFDO+LVWRU\
$W9LVLWSDWLHQWVZLOOEHTXHVWLRQHGDERXWPHGLFDOKLVWRU\LQFOXGLQJDFXWHDQGFKURQLFPHGLFDO
KLVWRU\DQGPHGLFDOKLVWRU\UHOHYDQWWRWKHLUDWRSLFGHUPDWLWLVDVZHOODVDOOPHGLFDWLRQXVHZLWKLQWKH
SDVWZHHNV
 9LWDO6LJQV
7KHSDWLHQW¶VYLWDOVLJQVZLOOEHUHFRUGHGKHDUWUDWHEORRGSUHVVXUHWHPSHUDWXUHDQGUHVSLUDWLRQUDWH
DW9LVLWDQG

3K\VLFDO([DPDQG%RG\6XUIDFH$UHD%6$
$JHQHUDOSK\VLFDOH[DPZLOOEHFRQGXFWHGDW9LVLWDQG9LVLW $W9LVLWWKHSDWLHQW¶VKHLJKW
PHWHUVDQGZHLJKWNJZLOOEHPHDVXUHG7KHKHLJKWDQGZHLJKWZLOOEHUHFRUGHGDQGWKH%RG\
6XUIDFH$UHD%6$ZLOOEHFDOFXODWHGVHH$SSHQGL[$IRUFRQYHUVLRQVIURPLQFKHVDQGSRXQGVDV
DSSURSULDWH$W9LVLWDQGWKH%6$DIIHFWHGZLOOEHUHFRUGHGVHH$SSHQGL[$

'HUPDWRORJLFDO$VVHVVPHQW
$W9LVLWDYLVXDOLQVSHFWLRQWRFRQILUPDGLDJQRVLVRIPRGHUDWHWRVHYHUHDWRSLFGHUPDWLWLVZLOOEH
GRQH$WHDFKYLVLWDWRSLFGHUPDWLWLVZLOOEHDVVHVVHGDFFRUGLQJWRWKHIROORZLQJPHDVXUHV
·
,*$6FRUH$SSHQGL[&
·
6LJQVDQG6\PSWRPV$VVHVVPHQWVDQG($6,6FRUH$SSHQGL[%
·
$SSOLFDWLRQ6LWH5HDFWLRQV$SSHQGL['
3DWLHQWV ZLOO DOVR EH DVNHG WR UDWH WKH VHYHULW\ RI SUXULWXV RYHU WKH SUHYLRXV KRXUV XVLQJ VFDOH
SURYLGHGLQ$SSHQGL[%:KHQHYHUSRVVLEOHWKHVDPH,QYHVWLJDWRUVKRXOGSHUIRUPGHUPDWRORJLFDO
DVVHVVPHQWVIRUDJLYHQSDWLHQW

&RQFRPLWDQW0HGLFDWLRQ8VH
$W 9LVLWV  SDWLHQWV ZLOO EH TXHVWLRQHG DERXW FXUUHQW DQG FRQFRPLWDQW PHGLFDWLRQ XVH RYHU WKH
SUHYLRXV  ZHHNV  $W DOO YLVLWV SDWLHQWV ZLOO EH TXHVWLRQHG DERXW RQJRLQJ RU QHZ FRQFRPLWDQW
PHGLFDWLRQXVH

3UHJQDQF\7HVW
8ULQHSUHJQDQF\WHVWVRQIHPDOHVRIFKLOGEHDULQJSRWHQWLDOZLOOEHSHUIRUPHGDW9LVLWDQG7KH
WHVWPXVWEHQHJDWLYHIRUWKHSDWLHQWWREHHOLJLEOHIRULQFOXVLRQLQWKHVWXG\,IWKHSDWLHQWLVRIQRQ
FKLOGEHDULQJ SRWHQWLDO WKH VRXUFH GRFXPHQW PXVW OLVW WKH UHDVRQ ZK\ VKH LV RI QRQFKLOGEHDULQJ
SRWHQWLDOHJSUHPHQDUFKDO
$Q\ SDWLHQW ZKR EHFRPHV SUHJQDQW GXULQJ WKH VWXG\ PXVW EH GLVFRQWLQXHG DQG (QG RI 6WXG\
SURFHGXUHVFRPSOHWHG7KHRXWFRPHRIWKHSUHJQDQF\ZLOOEHIROORZHGE\WKH,QYHVWLJDWRUWRELUWKRU
HDUO\WHUPLQDWLRQDVDSSURSULDWH7KHSUHJQDQF\ZLOOEHUHSRUWHGDVDQ$(


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




'LVSHQVLQJ6WXG\'UXJ
$W9LVLWSDWLHQWVWKDWVDWLVI\DOORIWKHLQFOXVLRQH[FOXVLRQFULWHULDZLOOEHGLVSHQVHGRQHERWWOHRIWKH
VWXG\GUXJDQGGRVLQJLQVWUXFWLRQV$W9LVLW'D\DQHZERWWOHRIVWXG\GUXJZLOOEHGLVSHQVHG
7KHZHLJKWRIWKHVWXG\GUXJSURGXFWVKRXOGEHUHFRUGHGEHIRUHGLVSHQVLQJ7KHSDWLHQWZLOOEH
LQVWUXFWHGWRDSSO\WKHILUVWGRVHRIVWXG\GUXJGXULQJ9LVLWXQGHUVWDIIVXSHUYLVLRQ
 &ROOHFWLQJ6WXG\'UXJ
6WXG\PHGLFDWLRQERWWOHVZLOOEHFROOHFWHGDQGZHLJKWHGDW9LVLWVDQG
 'RVLQJ,QVWUXFWLRQVDQG'LDU\
3DWLHQWV ZLOO EH SURYLGHG ZLWK D GLDU\ WR UHFRUG WKH WLPH DQG GDWH RI GRVLQJ RWKHU FRQFRPLWDQW
PHGLFDWLRQV DQG DGYHUVH HYHQWV  3DWLHQWV DSSO\LQJ IHZHU WKDQ  RU PRUH WKDQ  RI WKH
UHTXLUHG GRVHV ZLOO EH FRQVLGHUHG QRQFRPSOLDQW ZLWK GRVLQJ  &RPSOLDQFH ZLWK GRVLQJ ZLOO EH
YHULILHGE\WKHXVHRIWKHSDWLHQWGLDULHV
 'RVLQJ&RPSOLDQFH
'RVLQJFRPSOLDQFHZLOOEHFKHFNHGE\VLWHVWDIIDW9LVLWVDQG3DWLHQWVWDNLQJIHZHUWKDQRU
PRUHWKDQRIWKHVFKHGXOHGGRVHVZLOOEHFRQVLGHUHGQRQFRPSOLDQWZLWKGRVLQJ&RPSOLDQFH
ZLWKGRVLQJZLOOEHYHULILHGE\WKHXVHRIWKHSDWLHQWGLDULHV
 6WDQGDUG6XQVFUHHQDQG3DWLHQW:ULVWEDQG
$OOSDWLHQWVZLOOEHDGYLVHGWRDYRLGVXQH[SRVXUH$VWDQGDUGVXQVFUHHQZLOOEHSURYLGHGDW9LVLW
VKRXOGWKHXVHRIVXQVFUHHQEHZDUUDQWHG(DFKSDWLHQWZKRHQWHUVWKHVWXG\ZLOOEHSURYLGHGZLWKD
ZULVWEDQGDW9LVLWWRLGHQWLI\WKDWWKHSDWLHQWLVWDNLQJDPHGLFDWLRQWKDWFRXOGSRWHQWLDOO\FDXVH
+3$D[LVVXSSUHVVLRQ7KHSDWLHQWVKRXOGEHLQVWUXFWHGWRZHDUWKHZULVWEDQGIRUWKHGXUDWLRQRIWKH
VWXG\
 /DERUDWRU\(YDOXDWLRQ
$W9LVLWDQG9LVLWDEORRGVDPSOHZLOOEHFROOHFWHGIRUKHPDWRORJ\DQGFOLQLFDOFKHPLVWU\WHVWLQJ
6HH$SSHQGL[) 
 &RUWLVRO5HVSRQVH7HVW
$W 9LVLW  DQG 9LVLW  DOO SDWLHQWV ZLOO KDYH D FRUWLVRO UHVSRQVH WHVW SHUIRUPHG DFFRUGLQJ WR WKH
SURFHGXUH GHWDLOHG LQ $SSHQGL[ (  7KH UHVXOWLQJ EORRG VDPSOH VKRXOG EH VHQW WR $&0 *OREDO
/DERUDWRU\IRULPPHGLDWHWHVWLQJ
9LVLW7HVW
7KHWHVWDWWKH(QGRI6WXG\YLVLWVKRXOGQRWEHSHUIRUPHGLIWKHSDWLHQWGRVHGZLWKLQKRXUV
$SDWLHQWZLOOEHFRQVLGHUHGWRKDYHQRUPDOEDVDOFRUWLVROOHYHODQGDGUHQDOIXQFWLRQLIWKH\PHHWDOO
WKUHH FULWHULD OLVWHG EHORZ XQGHU 1RUPDO  )DLOXUH WR PHHW DQ\ RI WKHVH FULWHULD LV LQGLFDWLYH RI
DEQRUPDODGUHQDOIXQFWLRQRUSRWHQWLDO+3$D[LVVXSSUHVVLRQHYHQLQDEVHQFHRIUHODWHGV\PSWRPV
HJQDXVHDKHDGDFKHP\DOJLDIDWLJXHRUORRVHVWRROLQFDVHRIDEQRUPDOUHVXOWVWKHSDWLHQWZLOOEH
PRQLWRUHGLQDFFRUGDQFHWRWKHIROORZXSVFKHGXOHEHORZ

&RUWLVRO5HVXOWV
1RUPDO
$EQRUPDO


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



%DVDO
SUH&RUWURV\Q70
LQMHFWLRQ
PFJPO
PFJPO
PLQXWHVSRVW
&RUWURV\Q70LQMHFWLRQ
EDVDOYDOXH
EDVDOYDOXH
!PFJPO
PFJPO
+3$$[LVVXSSUHVVLRQZLOOEHGHILQHGDVDPLQXWHSRVW&RUWURV\Q70LQMHFWLRQOHYHOFRUWLVROOHYHO
RIPFJPO$VWKHVWXG\WUHDWPHQWSHULRGZLOOEHRYHUDQ\SDWLHQWVZLWKUHVXOWVRI+3$D[LV
VXSSUHVVLRQZLOOEHDGYLVHGQRWWRLQLWLDWHDQ\QHZVWHURLGWKHUDS\WRSLFDORURWKHUZLVHDQGWRUHWXUQ
WRWKHVLWHLQGD\VDWZKLFKWLPHWKH\ZLOOEHDVVHVVHGIRU+3$D[LVVXSSUHVVLRQ
$Q\SDWLHQWSUHVHQWLQJZLWKV\PSWRPVRI+3$D[LVVXSSUHVVLRQVXFKDVQDXVHDKHDGDFKHP\DOJLD
IDWLJXH RU ORRVH VWRRO ZLOO EH UHIHUUHG WR DQ HQGRFULQRORJLVW $V DQ DGGLWLRQDO VDIHW\ SUHFDXWLRQ
ZULVWEDQGVLGHQWLI\LQJWKHSDWLHQWDVVRPHRQHVXIIHULQJIURPDGUHQDOVXSSUHVVLRQVHFRQGDU\WRVWHURLG
ZLWKGUDZDOZLOOEHSURYLGHGWRDOHUWPHGLFDOSHUVRQQHOVKRXOGDQ\HPHUJHQFLHVDULVHEHIRUHDGUHQDO
IXQFWLRQUHWXUQVWRQRUPDO
,I WKH UHVXOWV RI WKH FRUWLVRO UHVSRQVH WHVW VWLOO VKRZ VLJQV RI +3$ D[LV VXSSUHVVLRQ  GD\V DIWHU
GLVFRQWLQXLQJ WKHUDS\ WKH SDWLHQW ZLOO EH DVNHG WR UHWXUQ LQ  GD\V  GD\V DIWHU GLVFRQWLQXLQJ
VWHURLG WKHUDS\ IRU DQRWKHU IROORZXS WHVW ,I WKH SDWLHQW LV VWLOO VKRZLQJ VLJQV RI +3$ D[LV
VXSSUHVVLRQ  GD\V DIWHU GLVFRQWLQXLQJ VWHURLG WKHUDS\ DQG SUHVHQWV ZLWK UHODWHG V\PSWRPV WKH
SDWLHQWZLOOEHUHIHUUHGWRDQHQGRFULQRORJLVW
,I+3$D[LVVXSSUHVVLRQSHUVLVWVIRUGD\VDIWHUGLVFRQWLQXLQJVWHURLGWKHUDS\EXWWKHSDWLHQWKDVQR
V\PSWRPVWKH\ZLOOEHDVNHGWRUHWXUQLQGD\VGD\VDIWHUGLVFRQWLQXLQJVWHURLGWKHUDS\IRU
DQRWKHU IROORZXS WHVW ,I +3$ D[LV VXSSUHVVLRQ SHUVLVWV IRU  GD\V DIWHU GLVFRQWLQXLQJ VWHURLG
WKHUDS\WKHSDWLHQWZLOOEHUHIHUUHGWRDQHQGRFULQRORJLVWUHJDUGOHVVRIV\PSWRPV
3DWLHQWV VKRXOG QRW EH VXEMHFWHG WR &RUWURV\Q70 WHVWLQJ RU DQ\ RWKHU FKDOOHQJH WR WKHLU DGUHQDO
UHVSRQVHDQ\VRRQHUWKDQZHHNVIURPWKHLUODVW&RUWURV\Q70WHVW

)ROORZ8S6FKHGXOHIRU3DWLHQWVVKRZLQJVLJQVRI+3$$[LV6XSSUHVVLRQ
'D\V
DIWHUGF
+3$5HVXOWV
6\PSWRPV
3DWLHQW&RXUVH

1RUPDO
1$
6WXG\RYHU

$EQRUPDO
<HV
5HIHUWRHQGRFULQRORJLVW

$EQRUPDO
1R
5HSHDWWHVWLQGD\V

1RUPDO
1$
6WXG\RYHU

$EQRUPDO
<HV
5HIHUWRHQGRFULQRORJLVW

$EQRUPDO
1R
5HSHDWWHVWLQGD\V

1RUPDO
1$
6WXG\RYHU

$EQRUPDO
<HVRU1R
5HIHUWRDQHQGRFULQRORJLVW


$GYHUVH(YHQWV
7KH SDWLHQWV ZLOO EH PRQLWRUHG WKURXJKRXW WKH VWXG\ IRU DQ\ $GYHUVH (YHQWV $( $(V ZLOO EH
FROOHFWHGWKURXJKERWKVROLFLWHGDQGXQVROLFLWHGPHDQVDQGVXEVHTXHQWO\FRGHGLQWDEXODUIRUPXVLQJ
WKH0HG'5$9HUVLRQRUKLJKHU$GYHUVH(YHQW'LFWLRQDU\7KHSDWLHQWVZLOOEHHQFRXUDJHGWR
UHSRUW VLJQV V\PSWRPV DQG DQ\ FKDQJHV LQ KHDOWKWR WKH FOLQLF VWDII  6HYHULW\RI HDFK $( ZLOO EH
GHWHUPLQHGE\WKHVWDIIEDVHGRQREVHUYDWLRQDQGTXHVWLRQLQJRIWKH SDWLHQWV7KH,QYHVWLJDWRUZLOO


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



MXGJHWKHUHODWLRQVKLSRIWKHHYHQWWRWKHVWXG\WUHDWPHQWV$GYHUVHHYHQWVVKRXOGEHIROORZHGXSXQWLO
WKH\KDYHUHVROYHGRUVWDELOL]HG

$GYHUVH(YHQW'HILQLWLRQV
$GYHUVH (YHQW $Q\ XQWRZDUG PHGLFDO RFFXUUHQFH LQ D SDWLHQW RU FOLQLFDO LQYHVWLJDWLRQ SDWLHQW
DGPLQLVWHUHGDSKDUPDFHXWLFDOSURGXFWDQGZKLFKGRHVQRWQHFHVVDULO\KDYHDFDXVDOUHODWLRQVKLSZLWK
WUHDWPHQW $Q $( FDQ WKHUHIRUH EH DQ\ XQIDYRUDEOH DQG XQLQWHQGHG VLJQ V\PSWRP RU GLVHDVH
WHPSRUDOO\DVVRFLDWHGZLWKWKHXVHRIDPHGLFLQDOLQYHVWLJDWLRQDOSURGXFWZKHWKHURUQRWUHODWHGWR
WKLVSURGXFW7KLVLQFOXGHVHYHQWVQRWVHHQDWEDVHOLQHRUZRUVHQHGHYHQLISUHVHQWDWEDVHOLQH
8QH[SHFWHG$GYHUVH(YHQW$QDGYHUVHHYHQWZKHUHWKHQDWXUHRUVHYHULW\RILVQRWFRQVLVWHQWZLWK
WKHDSSOLFDEOHSURGXFWLQIRUPDWLRQHJ,QYHVWLJDWRU¶V%URFKXUHIRUDQXQDSSURYHGLQYHVWLJDWLRQDO
SURGXFWRUSDFNDJHLQVHUWVXPPDU\RISURGXFWFKDUDFWHULVWLFVIRUDQDSSURYHGSURGXFW
$GYHUVH'UXJ5HDFWLRQ$OOQR[LRXVDQGXQLQWHQGHGUHVSRQVHVWRDPHGLFDOSURGXFWUHODWHGWRDQ\
GRVHVKRXOGEHFRQVLGHUHGDGYHUVHGUXJUHDFWLRQV7KHUHVSRQVHWRDµPHGLFDOSURGXFW¶PHDQVWKDWD
FDXVDO UHODWLRQVKLS EHWZHHQ D PHGLFLQDO SURGXFW DQG DQ DGYHUVH HYHQW LV DW OHDVW D UHDVRQDEOH
SRVVLELOLW\LHWKHUHODWLRQVKLSFDQQRWEHUXOHGRXW
 6HYHULW\RI$GYHUVH(YHQW
7KHVHYHULW\RIWKHDGYHUVHHYHQWZLOOEHJUDGHGE\WKH,QYHVWLJDWRUXVLQJWKHIROORZLQJFULWHULDDV
JXLGHOLQHV
·
0,/'$ZDUHQHVVRIV\PSWRPEXWGRHVQRWLQWHUIHUHZLWKURXWLQHDFWLYLWLHV
·
02'(5$7('LVFRPIRUWVXIILFLHQWWRLQWHUIHUHZLWKURXWLQHDFWLYLWLHV
·
6(9(5(,PSRVVLEOHWRSHUIRUPURXWLQHDFWLYLWLHV
 5HODWLRQVKLSRI$GYHUVH(YHQW
5HODWLRQVKLSWRWKH6WXG\3URGXFW
·
1275(/$7('$Q\$(WKDWLVFOHDUO\QRWUHODWHGWRXVHRIWKHVWXG\GUXJ
·
3266,%/( 7KH DVVRFLDWLRQ RI WKH $( ZLWK WKH VWXG\ GUXJ LV XQNQRZQ KRZHYHU D
UHODWLRQVKLSEHWZHHQWKHGUXJDQGHYHQWFDQQRWEHUXOHGRXW
·
352%$%/(7KHUHLVUHDVRQDEOHWHPSRUDOUHODWLRQVKLSEHWZHHQWKHXVHRIWKHVWXG\GUXJ
DQGWKH$(%DVHGXSRQWKH,QYHVWLJDWRU¶VFOLQLFDOH[SHULHQFHWKHDVVRFLDWLRQRIWKHHYHQW
ZLWKWKHVWXG\GUXJVHHPVOLNHO\
·
'(),1,7(7KH$(RFFXUVIROORZLQJWKHDSSOLFDWLRQRIWKHVWXG\GUXJDQGLWFDQQRWEH
UHDVRQDEO\ H[SODLQHG E\ DQ\ RWKHU NQRZQ FKDUDFWHULVWLFV RI WKH SDWLHQW¶V FOLQLFDO VWDWH
HQYLURQPHQWDORUWR[LFIDFWRUVRURWKHUPRGHVRIWUHDWPHQWDGPLQLVWHUHGWRWKHSDWLHQW,W
GLVDSSHDUVRUGHFUHDVHVXSRQGLVFRQWLQXDWLRQRIWKHVWXG\PHGLFDWLRQDQGUHDSSHDUVRQD
UHFKDOOHQJHRIWKHVWXG\GUXJ


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



3DWLHQW¶V3DUWLFLSDWLRQ6WRSSLQJ&ULWHULD
,QWKHRSLQLRQRIWKH,QYHVWLJDWRULIWKHSDWLHQWVXIIHUVDQ$(WKDWZDUUDQWVGLVFRQWLQXDWLRQRIWKHVWXG\
GUXJ GXH WR LQWHUIHUHQFH ZLWK DJHDSSURSULDWH LQVWUXPHQWDO $'/ $FWLYLWLHV RI 'DLO\ /LYLQJ IRU
H[DPSOHSUHSDULQJIRUPHDOVKRSSLQJIRUJURFHULHVRUFORWKLQJXVLQJWKHWHOHSKRQHHWFWKHSDWLHQWZLOO
EHIROORZHGXQWLOWKH$(UHVROYHVRULVFRQVLGHUHGVWDEOH$Q\VXEMHFWWKDWGLVFRQWLQXHVWKHVWXG\GXHWR
DQDGYHUVHHYHQWZLOOEHIROORZHGXQWLOUHVROXWLRQRUVWDELOL]DWLRQRIWKHDGYHUVHHYHQW

6HULRXV$GYHUVH(YHQWV

'HILQLWLRQRID6HULRXV$GYHUVH(YHQW
$6HULRXV$GYHUVH(YHQW6$(LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHWKDWDWDQ\GRVHVXJJHVWVD
PHGLFDOO\VLJQLILFDQWKD]DUGLQFOXGLQJDQ\HYHQWWKDW
·
5HVXOWVLQGHDWK±LQFOXGHVDOOGHDWKVHYHQWKRVHWKDWDSSHDUWREHFRPSOHWHO\XQUHODWHGWR
VWXG\WUHDWPHQWHJFDUDFFLGHQWZKHUHSDWLHQWLVDSDVVHQJHU
·
,VOLIH±WKUHDWHQLQJ±LQWKHYLHZRIWKH,QYHVWLJDWRUWKHSDWLHQWLVDWLPPHGLDWHULVNRIGHDWKDW
WKHWLPHRIWKHHYHQW
·
5HVXOWV LQ SHUVLVWHQW RU VLJQLILFDQW GLVDELOLW\ RU LQFDSDFLW\ VXEVWDQWLDO GLVUXSWLRQ RI RQH¶V
DELOLW\WRFRQGXFWQRUPDOOLIH
·
5HTXLUHVLQSDWLHQWKRVSLWDOL]DWLRQRUSURORQJDWLRQRIH[LVWLQJKRVSLWDOL]DWLRQ
·
&DXVHVFRQJHQLWDODQRPDO\RUELUWKGHIHFW
·
,VDQLPSRUWDQWPHGLFDOHYHQWWKDWPD\QRWEHLPPHGLDWHO\OLIHWKUHDWHQLQJRUUHVXOWLQGHDWK
RU KRVSLWDOL]DWLRQ EXW PD\ MHRSDUGL]H WKH SDWLHQW RU PD\ UHTXLUH PHGLFDO RU VXUJLFDO
LQWHUYHQWLRQWRSUHYHQWRQHRIWKHVHULRXVRXWFRPHVOLVWHGDERYHHJLQWHQVLYHWUHDWPHQWLQ
DQ HPHUJHQF\ URRP FRQYXOVLRQV WKDW GR QRW UHVXOW LQ KRVSLWDOL]DWLRQV (PHUJHQF\ 5RRP
YLVLWV WKDW UHTXLUH PHGLFDO RU VXUJLFDO LQWHUYHQWLRQ WR SUHYHQW RQH RI WKH RWKHU VHULRXV
RXWFRPHVOLVWHGDERYHDUHFRQVLGHUHGD6HULRXV$GYHUVH(YHQW
 5HSRUWLQJ6HULRXV$GYHUVH(YHQWV
,QYHVWLJDWRU5HSRUWLQJRI6$(V
$GYHUVHHYHQWVZKLFKDUHHYDOXDWHGE\WKH,QYHVWLJDWRUDV6HULRXVZLOOEHUHSRUWHGWRWKH6SRQVRU
DQG,5%ZLWKLQKRXUVRIQRWLFHZKHWKHURUQRWWKH\DUHFRQVLGHUHGH[SHFWHGRUGUXJUHODWHG$OO
6$(VZLOOEHUHSRUWHGDVSHUDSSOLFDEOHUHJXODWLRQV$OO6$(VHQFRXQWHUHGGXULQJWKHVWXG\ZLOOEH
UHSRUWHGRQWKHDSSURSULDWHIRUPDQGVXPPDUL]HGLQWKHILQDOUHSRUW
$Q\ VHULRXV RU XQH[SHFWHG DGYHUVH HYHQWV VKRXOG EH UHSRUWHG WR 1RYXP ZLWKLQ  KRXUV
)ROORZLQJLVWKHFRQWDFWLQIRUPDWLRQ
*DLO*RQJDV
9LFH3UHVLGHQW&OLQLFDO7ULDOV
&HOO3KRQH
3KRQH[
)D[
2U


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



3DROR)DQ]LR0'

0HGLFDO0RQLWRU

3KRQH[
)D[
1RYXPZLOOUHSRUWDQ\6HULRXV$GYHUVH(YHQWWR7DUR
'RFXPHQWDWLRQVKRXOGEHVHQWWR7DUR¶V6WXG\0DQDJHUDQGRU7DUR¶V'UXJ6DIHW\'HSDUWPHQWOLVWHG
EHORZ
7DUR6WXG\0DQDJHU
7DUR'UXJ6DIHW\0DQDJHU
1DWDOLH<DQWRYVNL\
'LUHFWRU&OLQLFDO5HVHDUFK
7DUR3KDUPDFHXWLFDOV86$,QF
6N\OLQH'ULYH
+DZWKRUQH1<
3KRQH[
(PDLO$QJHOOD6LO\H#7DURFRP
0DUJR/DF\:\DWW51%61
$VVRFLDWH'LUHFWRU'UXJ6DIHW\
7DUR3KDUPDFHXWLFDOV86$,QF
6N\OLQH'ULYH+DZWKRUQH1<
([W
(PDLO0DUJR:\DWW#WDURFRP
DQG7$523986#7$52FRP
,QYHVWLJDWRUVZLOOEHLQIRUPHGRIDQ\6$(VUHSRUWHGDWRWKHUVWXG\VLWHVZLWKLQGD\VIURPWKHLQLWLDO
UHSRUW

67$7,67,&$/0(7+2'6

6WDWLVWLFDO3ODQ
$6WDWLVWLFDO$QDO\VLV3ODQ6$3GHWDLOLQJWKHLQWHQGHGVWDWLVWLFDODQDO\VLVRIWKHVWXG\GDWDZLOOEH
SUHSDUHGDVDVHSDUDWHGRFXPHQWDQGILQDOL]HGSULRUWRGDWDEDVHORFN$Q\GHYLDWLRQIURPWKHRULJLQDO
VWDWLVWLFDOSODQZLOOEHGHVFULEHGDQGMXVWLILHGLQWKHILQDOUHSRUWDVDSSURSULDWH7KHSURFHGXUHIRU
DFFRXQWLQJIRUPLVVLQJXQXVHGDQGVSXULRXVGDWDZLOOEHLQFOXGHGLQWKH6WDWLVWLFDO$QDO\VLV3ODQ
$OOVWDWLVWLFDODQDO\VLVZLOOEHFRQGXFWHGXVLQJ6$69HUVLRQRUKLJKHU
 'HWHUPLQDWLRQRI6DPSOH6L]H
7KHVDPSOHVL]HRISDWLHQWVVWUDWLILHGE\DJHDQG%6$ZDVGHWHUPLQHGWREHVXIILFLHQW
 %DVHOLQH&RPSDUDELOLW\
%DVHOLQHFRPSDUDELOLW\RIWKHWZRJURXSVZLOOEHDVVHVVHGXVLQJDSSURSULDWHVWDWLVWLFDOWHVWVHJRQH
ZD\ DQDO\VLV RI YDULDQFH)LVKHU¶V H[DFW WHVW &RFKUDQ0DQWHO+DHQV]HO WHVW 7KH JURXSV ZLOO EH
FRPSDUHG IRU EDVLF GHPRJUDSKLFV DJH JHQGHU HWKQLFLW\ DQG UDFH EDVHOLQH ,*$ EDVHOLQH ($6,
VFRUHDQGEDVHOLQHWRWDO%6$6XPPDU\WDEOHVE\JURXSZLOOEHSUHVHQWHG
 6DIHW\$QDO\VLVRI3RWHQWLDO+3$$[LV6XSSUHVVLRQ
'RVLQJZLOOEHWZLFHDGD\IRUGD\VH[FOXGLQJWKHGRVHVSULRUWRWKH&RUWLVRO5HVSRQVH7HVW
DSSOLFDWLRQV$OOSDWLHQWVZKRDUHHQUROOHGXVHDWOHDVWGRVHVRIWKHVWXG\GUXJDQGKDYHGDWD


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



IURPDSRVWWUHDWPHQWFRUWLVROUHVSRQVHWHVWZLOOEHLQFOXGHGLQWKHDQDO\VLV3DWLHQWVZKRKDYHQRW
XVHGGRVHVRIWKHVWXG\GUXJZLOOEHH[FOXGHGIURPWKHSULPDU\DQDO\VLVRI+3$D[LVVXSSUHVVLRQ

7KHSULPDU\DQDO\VLVRILQWHUHVWLVWKHSURSRUWLRQRISDWLHQWVLQHDFKJURXSZKRDUHFRQVLGHUHGWR
KDYHGHPRQVWUDWHGSRVVLEOH+3$D[LVVXSSUHVVLRQIROORZLQJWUHDWPHQWZLWKWKHVWXG\PHGLFDWLRQ
$VDVHFRQGDU\DQDO\VLVRIWKHGDWDDORJLVWLFUHJUHVVLRQRIWKHSURSRUWLRQRISDWLHQWVLQWKHVWXG\
ZLWK+3$D[LVVXSSUHVVLRQZLOOEHSHUIRUPHGZLWK%6$DIIHFWHGDVDFRYDULDWH6HH$SSHQGL[(
IRUUHVXOWVIURPWKHFRUWLVROUHVSRQVHWHVWFRQVLGHUHGLQGLFDWLYHRISRWHQWLDO+3$D[LVVXSSUHVVLRQ

7KHVWXG\ZLOOEHHQUROOHGE\&RKRUWVWDUWLQJZLWK&RKRUWDQGHDFKFRKRUWZLOOEHUHYLHZHGIRUWKH
SRWHQWLDORI+3$D[LVVXSSUHVVLRQ,IDWOHDVWRISDWLHQWVLQ&RKRUWH[SHULHQFH+3$D[LV
VXSSUHVVLRQRQFHWKHPLQLPXPQXPEHURISDWLHQWVKDVEHHQHQUROOHGDQGFRPSOHWHGWKHFRKRUW
HQUROOPHQWIRUWKDWFRKRUWZLOOEHVWRSSHGDQGQRIXUWKHUFRKRUWVZLOOEHLQLWLDWHG,IDWOHDVWRI
SDWLHQWVKDYHH[SHULHQFHG+3$D[LVVXSSUHVVLRQDFURVVFRKRUWVFRPELQHGGXULQJWKHVWXG\
HQUROOPHQWZLOOEHGLVFRQWLQXHGDQGQRRWKHUFRKRUWVZLOOEHLQLWLDWHG&RKRUWZLOOQRWEHJLQXQWLO
VDIHW\GDWDKDVEHHQUHYLHZHGIRU&RKRUW7KHVDPHSURFHVVZLOOEHIROORZHGIRUHDFK&RKRUWXQWLO
WKHVWXG\LVFRPSOHWH

)RUDOOSDWLHQWVWKHDFWXDODPRXQWRIGHVR[LPHWDVRQHPJDSSOLHGGXULQJWKHVWXG\ZLOOEH
FDOFXODWHGIURPUHFRUGHGERWWOHZHLJKWVDQGSUHVHQWHG


6DIHW\$QDO\VLV
6DIHW\DQDO\VLVZLOOEHFRQGXFWHGRQDOOSDWLHQWVZKRDSSOLHGDWOHDVWRQHGRVHRIVWXG\GUXJ
$GYHUVHPHGLFDOHYHQWVH[SHULHQFHGE\WKHSDWLHQWVZLOOEHWDEXODWHG7KHUHODWLRQVKLSRI$(VLI
DQ\WRWKHVWXG\GUXJZLOOEHDVVHVVHGE\WKH,QYHVWLJDWRU$GYHUVHHYHQWVDVVHVVHGDVGHILQLWH
SUREDEOH SRVVLEOH RU QRW UHODWHG WR WKH VWXG\ GUXJ ZLOO EH SUHVHQWHG 6KLIW DQDO\VLV XVLQJ WKH
FDWHJRULHVEHORZDERYHDQGZLWKLQWKHODERUDWRU\QRUPDOUDQJHZLOOEHSHUIRUPHGWRLGHQWLI\DQ\
VSHFLILFODERUDWRU\SDUDPHWHUWKDWVKRZVDWUHQGWRZDUGSRWHQWLDOO\FOLQLFDOO\VLJQLILFDQWFKDQJHV


5(*8/$725<2%/,*$7,216

,QVWLWXWLRQDO5HYLHZ%RDUG
7KH VWXG\ SURWRFRO LQIRUPHG FRQVHQWDVVHQW IRUP ,QYHVWLJDWRU
V %URFKXUH RU SDFNDJH LQVHUW DV
DSSOLFDEOH DQG DQ\ VSHFLILF DGYHUWLVLQJ ZLOO EH VXEPLWWHG WR DQG DSSURYHG E\ DQ ,QVWLWXWLRQDO
5HYLHZ %RDUG ,5% EHIRUH WKH VWDUW RI WKH VWXG\ $ IRUP PXVW EH VLJQHG E\ WKH FKDLUPDQ RU
GHVLJQHH RI WKH ,5% QRWLQJ WKH DSSURYDOV 7KLV QRWLILFDWLRQ RI WKHERDUG
V DSSURYDO DORQJ ZLWK D
GHVFULSWLRQE\SURIHVVLRQDQGJHQGHURIWKHERDUG
VFRPSRVLWLRQZLOOEHSURYLGHGWRWKH6SRQVRU

6WXG\'RFXPHQWDWLRQ
7KLVVWXG\ZLOOEHFRQGXFWHGLQFRPSOLDQFHZLWKWKHSURWRFRO*RRG&OLQLFDO3UDFWLFHV*&3VDQG
DOODSSOLFDEOHUHJXODWLRQVLQFOXGLQJWKH)HGHUDO)RRG'UXJDQG&RVPHWLFV$FW86DSSOLFDEOH&RGH
RI)HGHUDO5HJXODWLRQVWLWOHSDUWVDQGDQ\,5%UHTXLUHPHQWVUHODWLYHWRFOLQLFDO


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



VWXGLHV DQG WKH 'HFODUDWLRQ RI +HOVLQNL -XQH  DV PRGLILHG E\ WKH WK :RUOG 0HGLFDO
$VVRFLDWLRQ*HQHUDO$VVHPEO\2FWREHU
7KH,QYHVWLJDWRUZLOOSHUPLWWULDOUHODWHGPRQLWRULQJDXGLWV,5%UHYLHZDQGUHJXODWRU\LQVSHFWLRQV
SURYLGLQJGLUHFWDFFHVVWRVRXUFHGDWDGRFXPHQWV
 3URWRFRO
7KH,QYHVWLJDWRULQGLFDWHGRQ)'$)RUPZLOODFWDVWKH3ULQFLSDO,QYHVWLJDWRUDWHDFKVWXG\
VLWH3URWRFROVZLOOEHQRWHGDVDSSURYHGE\SODFHPHQWRIWKH1RYXP5HSUHVHQWDWLYH¶VVLJQDWXUHRQ
WKH FRYHU SDJH 7KH 6SRQVRU RI WKH VWXG\ ZLOO DOVR DSSURYH WKH SURWRFRO E\ KDYLQJ D VWXG\
UHVSRQVLEOHLQGLYLGXDOVLJQWKHSURWRFROFRYHUSDJH
 ,QIRUPHG&RQVHQW
$Q,QIRUPHG&RQVHQW)RUP,&)WKDWLQFOXGHVDOORIWKHUHOHYDQWHOHPHQWVFXUUHQWO\UHTXLUHGE\
)'$DQGORFDO6WDWHUHJXODWLRQVZLOOEHSURYLGHGWRHDFKSURVSHFWLYHVWXG\SDWLHQW¶VSDUHQWOHJDO
JXDUGLDQEHIRUHHQUROOPHQWLQWRWKHVWXG\,QDGGLWLRQVXEMHFWV\HDUVRIDJHZLOOEHSUHVHQWHG
ZLWK DQ $VVHQW )RUP  7KH W\SH DQG PHWKRG RI VWXG\ WHVWV WR EH DGPLQLVWHUHG DQ\ SRWHQWLDO RU
SRVVLEOHKD]DUGVDQGWKHSDWLHQW
VULJKWWRZLWKGUDZIURPWKHVWXG\DWDQ\WLPHZLOOEHH[SODLQHGWR
WKH SDWLHQWV E\ WKH ,QYHVWLJDWRU RUGHVLJQHH 2QFH WKH ,QYHVWLJDWRU RUGHVLJQHHLV DVVXUHGWKDW DQ
LQGLYLGXDO FDQGLGDWH XQGHUVWDQGV WKH LPSOLFDWLRQV RI SDUWLFLSDWLQJ LQ WKLV VWXG\ WKH SDUHQWOHJDO
JXDUGLDQZLOOEHDVNHGWRJLYHFRQVHQWE\VLJQLQJDQGGDWLQJWKH,&)$VVHQW)RUPDQGWKHSDWLHQW
ZLOO EH DVNHG WR JLYH DVVHQW E\ VLJQLQJ DQG GDWLQJ LQ WKH DSSURSULDWH DUHDV RI WKH $VVHQW 7KH
,QYHVWLJDWRURUGHVLJQHHZLOODOVRVLJQDQGGDWHWKHIRUPDORQJZLWKDVWDIIPHPEHUZKRZLOOVLJQ
WKH,&)DVDZLWQHVVWRYHULI\WKDWWKHSDWLHQWKDVLQGHHGUHFHLYHGLQIRUPDWLRQ)RULOOLWHUDWHSDWLHQWV
YHUEDOFRQVHQWVKRXOGEHREWDLQHGLQWKHSUHVHQFHRIDQGEHFRXQWHUVLJQHGE\DOLWHUDWHZLWQHVV,I
DQ\RWKHUODQJXDJHLVUHTXLUHGWUDQVODWLRQZLOOEHSHUIRUPHGE\DFHUWLILHGWUDQVODWRU$FRS\RIWKH
,&)ZLOOEHSURYLGHGWRWKHSDWLHQW
 3URWRFRODQG,QIRUPHG&RQVHQW&KDQJHV
5HYLVLRQVWRWKHRULJLQDOSURWRFROZLOOEHGRFXPHQWHGLQDPHQGPHQWVLQFRUSRUDWHGDVDSUHIDFHWR
WKHQHZYHUVLRQDQGDSSURYHGE\WKH,5%$Q\UHYLVLRQWKDWVXEVWDQWLDOO\DOWHUVWKHVWXG\GHVLJQRU
LQFUHDVHV SRWHQWLDO ULVN WR WKH SDWLHQW UHTXLUHV WKH SDWLHQW¶V FRQVHQW WR FRQWLQXH LQ WKH VWXG\
5HYLVLRQVWRWKHRULJLQDO,&)ZLOODOVREHDSSURYHGE\WKH,5%7KHDSSURYDOVZLOOEHSURFHVVHGLQ
DFFRUGDQFH ZLWK WKH HVWDEOLVKHG ,5% SURFHGXUHV &RSLHV RI DOO SURWRFRO DQG ,&)
DPHQGPHQWVUHYLVLRQVDORQJZLWKOHWWHUVQRWLQJ,5%DSSURYDOZLOOEHVXEPLWWHGWRWKH6SRQVRU
 6RXUFH'RFXPHQWVDQG&DVH5HSRUW)RUPV
$OO SDWLHQWV ZLOO EH LGHQWLILHG E\ LQLWLDOV GDWH RI ELUWK DQG D XQLTXH SDWLHQW QXPEHU 6RXUFH
GRFXPHQWVZLOOEHXVHGWRUHFRUGDOOVWXG\UHODWHGGDWD6RXUFHGRFXPHQWHQWULHVZLOOEHXVHGWR
FRPSOHWH&DVH5HSRUW)RUPV&5)V$VHWRI&5)VZLOOEHFRPSOHWHGIRUHDFKSDWLHQWHQUROOHGLQ
WKHVWXG\$OOGDWDDQG&5)VZLOOEHUHYLHZHGHYDOXDWHGDQGVLJQHGE\WKH,QYHVWLJDWRUDVUHTXLUHG
7KH RULJLQDO VRXUFH GRFXPHQWV DQG D FRS\ RI WKH FRUUHVSRQGLQJ &5)V ZLOO EH UHWDLQHG E\ WKH
,QYHVWLJDWRU 3DWLHQWV ZKR WHUPLQDWH HDUO\ IURP WKH VWXG\ ZLOO KDYH WKH HQG RI VWXG\ 9LVLW 
VRXUFH&5)FRPSOHWHG


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



 'UXJ$FFRXQWDELOLW\
$OO GUXJ UHFHLSW LQYHQWRU\ GLVSHQVLQJ GRVLQJ DQG UHFRQFLOLDWLRQ UHFRUGV ZLOO EH PDLQWDLQHG LQ
FRPSOLDQFHZLWK)HGHUDO5HJXODWLRQV7KHVWXG\GUXJZLOOEHGLVSHQVHGWRTXDOLILHGVWXG\SDWLHQWV
DFFRUGLQJWRHVWDEOLVKHGSURFHGXUHV$WWKHHQGRIWKHVWXG\DIWHUWKHGDWDEDVHKDVEHHQORFNHGDOO
XVHGDQGXQXVHGVWXG\GUXJZLOOEHUHWXUQHGWR1RYXP
 'UXJ6WRUDJH
$OOVWXG\GUXJZLOOEHVWRUHGDWFRQWUROOHGURRPWHPSHUDWXUH&)LQDVHFXUHSODFH
ZLWK DFFHVV E\ DXWKRUL]HG LQGLYLGXDOV RQO\ 7KH ,QYHVWLJDWRU ZLOO EH UHVSRQVLEOH IRU PDLQWDLQLQJ
DFFXUDWHUHFRUGVRIGUXJUHFHLSWGLVSHQVLQJDQGUHWXUQ$WWKHHQGRIWKHVWXG\DOOSDUWLDOO\XVHG
DQGXQXVHGVWXG\GUXJZLOOEHUHWXUQHGWR1RYXP
 3UHJQDQFLHV
3DWLHQWVZLWKDSRVLWLYHSUHJQDQF\WHVWGXULQJVFUHHQLQJZLOOQRWEHHQUROOHGLQWKHVWXG\3DWLHQWV
ZKRUHSRUWWKDWWKH\KDYHEHFRPHSUHJQDQWGXULQJWKHVWXG\RUKDYHDSRVLWLYHSUHJQDQF\WHVWDWDQ\
FOLQLFYLVLWZLOOEHIROORZHGWRFRPSOHWLRQRIWKHSUHJQDQF\7KHSUHJQDQF\ZLOOEHUHSRUWHGDVDQ
$(
)HPDOHSDWLHQWVRIFKLOGEHDULQJSRWHQWLDOPXVWKDYHEHHQXVLQJDQGPXVWDJUHHWRFRQWLQXHWRXVH
DFFHSWHGPHWKRGVRIELUWKFRQWUROWKURXJKRXWWKHVWXG\$OOIHPDOHSDWLHQWVDUHFRQVLGHUHGWREHRI
FKLOGEHDULQJ SRWHQWLDO XQOHVV WKH\ DUH SUHPHQDUFKDOKDYH EHHQ VXUJLFDOO\ VWHULOL]HG RU KDYH EHHQ
SRVWPHQRSDXVDOIRUDWOHDVW\HDU$EVWLQHQFHLVDQDFFHSWHGPHWKRGRIELUWKFRQWURO$OWHUQDWLYHO\
DQ\ RI WKH IROORZLQJ PHWKRGV RI ELUWK FRQWURO DUH DFFHSWDEOH RUDO FRQWUDFHSWLYHV FRQWUDFHSWLYH
SDWFKHVLPSODQWV HJ 1RUSODQW 'HSR3URYHUD GRXEOH EDUULHU PHWKRGV HJ FRQGRP DQG
VSHUPLFLGHRU,8'3ULRUWRVWXG\HQUROOPHQWZRPHQRIFKLOGEHDULQJSRWHQWLDOPXVWEHDGYLVHGRI
WKHLPSRUWDQFHRIDYRLGLQJSUHJQDQF\GXULQJVWXG\SDUWLFLSDWLRQ
$QHJDWLYHUHVXOWRIDXULQHSUHJQDQF\WHVWKDYLQJDPLQLPXPVHQVLWLYLW\RIDWOHDVWP,8POIRU
K&*VKRXOGEHREWDLQHGSULRUWRVWXG\SDUWLFLSDWLRQ3UHJQDQF\WHVWLQJZLOOEHSHUIRUPHGDW9LVLWV
DQGDQGWKHUHVXOWVRIDOOSUHJQDQF\WHVWVSRVLWLYHRUQHJDWLYHZLOOEHGRFXPHQWHG
,I IROORZLQJ LQLWLDWLRQ RI VWXG\ WUHDWPHQW LW LV VXEVHTXHQWO\ GLVFRYHUHG WKDW D VWXG\ SDWLHQW LV
SUHJQDQW RU PD\ KDYH EHHQ SUHJQDQW DW WKH WLPH RI ,QYHVWLJDWLRQDO 3URGXFW H[SRVXUH WKH
,QYHVWLJDWLRQDO 3URGXFW ZLOO EH SHUPDQHQWO\ GLVFRQWLQXHG 7KH 3ULQFLSDO ,QYHVWLJDWRU PXVW
LPPHGLDWHO\QRWLI\WKH0HGLFDO0RQLWRURIWKLVHYHQW
3URWRFROUHTXLUHG SURFHGXUHV IRU VWXG\ GLVFRQWLQXDWLRQ DQG IROORZXS PXVW EH SHUIRUPHG RQ WKH
SDWLHQW 2WKHU DSSURSULDWH SUHJQDQF\ IROORZXS SURFHGXUHV VKRXOG EH FRQVLGHUHG LI LQGLFDWHG ,Q
DGGLWLRQWKH3ULQFLSDO,QYHVWLJDWRUPXVWUHSRUWWRWKHVSRQVRUIROORZXSLQIRUPDWLRQUHJDUGLQJWKH
FRXUVHRIWKHSUHJQDQF\LQFOXGLQJSHULQDWDODQGQHRQDWDORXWFRPH,QIDQWVVKRXOGEHIROORZHGIRUD
PLQLPXPRIHLJKWZHHNVDIWHUELUWK
 5HSRUWLQJ6DIHW\,QIRUPDWLRQWRWKH,5%
7KH,QYHVWLJDWRUPXVWSURPSWO\UHSRUWWRWKH,QYHVWLJDWRU¶V,5%DOOXQDQWLFLSDWHGSUREOHPVLQYROYLQJ
ULVNVWRSDWLHQWV7KLVLQFOXGHVGHDWKIURPDQ\FDXVHDQGDOOVHULRXVDGYHUVHHYHQWVRFFXUULQJGXULQJ
WKHVWXG\UHJDUGOHVVRIWKHDVVHVVHGFDXVDOLW\


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



 5HFRUG5HWHQWLRQ
$OO GUXJ DFFRXQWDELOLW\ UHFRUGV &5)V VRXUFH GDWD DQG UHODWHG UHJXODWRU\ GRFXPHQWV PXVW EH
UHWDLQHGIRUDWOHDVWWHQ\HDUVIROORZLQJFRPSOHWLRQRIWKHVWXG\RUIRUWZR\HDUVDIWHUWKHWHVWSURGXFW
KDVEHHQDSSURYHGIRUPDUNHWLQJE\WKH)RRGDQG'UXJ$GPLQLVWUDWLRQ
6WXG\0RQLWRULQJDQG$XGLWLQJ
1RYXP ZLOO EH UHVSRQVLEOH IRU PRQLWRULQJ WKH VWXG\ DFFRUGLQJ WR *RRG &OLQLFDO 3UDFWLFH DQG
DSSOLFDEOHUHJXODWLRQV0RQLWRULQJYLVLWVDUHIRUWKHSXUSRVHRIFRQILUPLQJDGKHUHQFHWRWKHSURWRFRO
DQGWRYHULI\FRPSOHWHDQGDFFXUDWHGDWDFROOHFWLRQ7KHFOLQLFDOVLWHZLOOPDNHDOOUHFRUGVDVVRFLDWHG
ZLWKWKHVWXG\DYDLODEOHWR1RYXP¶VUHSUHVHQWDWLYHGXULQJVXFKYLVLWVDQGDXGLWV
7KH VWXG\ PD\ EH VXEMHFW WR DXGLW E\ WKH 6SRQVRU 6SRQVRU 5HSUHVHQWDWLYH RU E\ UHJXODWRU\
DXWKRULWLHV,IVXFKDQDXGLWRFFXUVWKH,QYHVWLJDWRUPXVWDJUHHWRDOORZDFFHVVWRUHTXLUHGSDWLHQW
UHFRUGV%\VLJQLQJWKLVSURWRFROWKH,QYHVWLJDWRUJUDQWVSHUPLVVLRQWRSHUVRQQHOIURPWKH6SRQVRU
LWV UHSUHVHQWDWLYHV DQG DSSURSULDWH UHJXODWRU\ DXWKRULWLHV IRU RQVLWH PRQLWRULQJ RI DOO DSSURSULDWH
VWXG\GRFXPHQWDWLRQDVZHOODVRQVLWHUHYLHZRIVWXG\SURFHGXUHV
(QGRIWKH7ULDO
7KHHQGRIWKHWULDOLVGHILQHGDVWKHWLPHDWZKLFKWKHODVWSDWLHQWKDVFRPSOHWHGWKHLUODVWYLVLWLQWKH
VWXG\8SRQFRPSOHWLRQRIWKHVWXG\WKHVWXG\GUXJZLOOQRORQJHUEHDYDLODEOHWRWKHSDWLHQWEXWWKH
,QYHVWLJDWRUFDQDWWKHLUGLVFUHWLRQGLVFXVVDOWHUQDWLYHWUHDWPHQWVZLWKWKHSDWLHQW
&OLQLFDO6WXG\5HSRUW
$WWKHHQGRIWKHVWXG\DIXOOUHSRUWLQH&7'IRUPDWZLOOEHSUHSDUHGWKDWZLOOLQFOXGHDQDUUDWLYHRI
WKHFOLQLFDOFRQGXFWDQGUHVXOWVRIWKHVWXG\DVWDWLVWLFDOUHSRUWLQFOXGLQJDGHVFULSWLRQRIWKHDQDO\VLV
SHUIRUPHGDQGRWKHUGRFXPHQWDWLRQDVPD\EHDSSURSULDWH




&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



 5()(5(1&(6



%HUNH56LQJK$	*XUDOQLFN0$WRSLFGHUPDWLWLVDQRYHUYLHZAmerican family 
physician

2QJ3<	/HXQJ'<7KHLQIHFWLRXVDVSHFWVRIDWRSLFGHUPDWLWLVImmunology and 
allergy clinics of North AmericaGRLMLDF

(LFKHQILHOG / ) et al. *XLGHOLQHV RI FDUH IRU WKH PDQDJHPHQW RI DWRSLF GHUPDWLWLV
VHFWLRQ  'LDJQRVLV DQG DVVHVVPHQW RI DWRSLF GHUPDWLWLV Journal of the American 
Academy of DermatologyGRLMMDDG

%UHQQLQNPHLMHU ( ( 6FKUDP 0 ( /HHIODQJ 0 0 %RV - ' 	 6SXOV 3 ,
'LDJQRVWLF FULWHULD IRU DWRSLF GHUPDWLWLV D V\VWHPDWLF UHYLHZ The British journal of 
dermatologyGRLM[

6FKQHLGHU/ et al.$WRSLFGHUPDWLWLVDSUDFWLFHSDUDPHWHUXSGDWHThe Journal of 
allergy and clinical immunologyHGRLMMDFL


/HXQJ ' < 1HZ LQVLJKWV LQWR DWRSLF GHUPDWLWLV UROH RI VNLQ EDUULHU DQG LPPXQH
G\VUHJXODWLRQ Allergology international : official journal of the Japanese Society of 
AllergologyGRLDOOHUJROLQW5$,

1RYDN 1 	 /HXQJ ' < $GYDQFHV LQ DWRSLF GHUPDWLWLV Current opinion in 
immunologyGRLMFRL

(LFKHQILHOG / ) et al. *XLGHOLQHV RI FDUH IRU WKH PDQDJHPHQW RI DWRSLF GHUPDWLWLV
VHFWLRQ0DQDJHPHQWDQGWUHDWPHQWRIDWRSLFGHUPDWLWLVZLWKWRSLFDOWKHUDSLHVJournal 
of the American Academy of DermatologyGRLMMDDG


1'$&RQQHWLFV)HEUXDU\

+HQJJH855X]LFDN76FKZDUW]5$&RUN0-$GYHUVHHIIHFWVRI7RSLFDO
*OXFRFRUWLFRVWHURLGV-$P$FDG'HUPDWRORJ\&RQWLQXLQJ0HGLFDO(GXFDWLRQ

3URGXFW/DEHOIRU723,&257GHVR[LPHWDVRQH7RSLFDO6SUD\$SULO

3URGXFW/DEHOIRU&RUWURV\Q70$PSKDVWDU3KDUPDFHXWLFDOV,QF$XJXVW

6XPPDU\%DVLVRI$SSURYDO2/8;FOREHWDVROIRDP1'$&RQQHWLFV
0D\

6XPPDU\%DVLVRI$SSURYDO/8;,4EHWDPHWKDVRQHIRDP

)'$&RUUHVSRQGHQFH0HHWLQJ0LQXWHV,1''HVR[LPHWDVRQH7RSLFDO6SUD\
'HSDUPHQWRI+HDOWKDQG+XPDQ6HUYLFHV)'$

0RVWHOOHU5%6LPSOLILHG&DOFXODWLRQRI%RG\6XUIDFH$UHD1(QJ-0HG2FW


)'$&RUUHVSRQGHQFH$GYLFH/HWWHU,1''HSDUWPHQWRI+HDOWKDQG+XPDQ
6HUYLFHV)'$






&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



$33(1',&(6

$33(1',;$%RG\6XUIDFH$UHD&DOFXODWLRQ

7RWDO%RG\6XUIDFH$UHD&DOFXODWLRQ

7RFDOFXODWHWKH7RWDO%6$WKHIROORZLQJSURFHGXUH0RVWHOOHU)RUPXODVKRXOGEHIROORZHG

7RWDO%RG\6XUIDFH$UHD%6$LQPHWHUVVTXDUHG

P KHLJKWFP[ZHLJKWNJò

7KHSDWLHQW¶VKHLJKWDQGZHLJKWVKRXOGEHUHSRUWHGWRWKHQHDUHVWFPDQGQHDUHVWNJ7KH%6$VKRXOG
EHUHSRUWHGWRWKHQHDUHVWVHFRQGGHFLPDOSODFH

)RUH[DPSOHDSDWLHQWZKRLVLQFKHVWDOODQGZHLJKVOEVZLOOKDYHDUHSRUWHG%6$RI
LQ[ FP
OE[ NJ

%6$
 6457[
 Pð

%6$$IIHFWHG

7RHVWLPDWHWKH%6$$IIHFWHGWKH,QYHVWLJDWRUVKRXOGXVHWKHPHWKRGRIDSSUR[LPDWLRQ

7KH³5XOHRI1LQHV´SURYLGHVDJHQHUDOHVWLPDWLRQRIWRWDO%6$IRUVHYHUDODQDWRPLFDUHDVHDFK
DUP HDFKOHJ EDFN FKHVWDQGDEGRPHQ KHDG JURLQ 7KH
,QYHVWLJDWRUPD\WKHQYLVXDOO\HVWLPDWHWKHSURSRUWLRQRIWKHLQYROYHGVNLQZLWKLQHDFKDQDWRPLF
DUHDDQGFDOFXODWHWKHWRWDOSHUFHQWDJHRI%6$DIIHFWHG,QFKLOGUHQKLSVDQGOHJVDUHVPDOOHUDQG
WKHKHDGQHFNDQGVKRXOGHUVDUHODUJHUDVDUHVXOWDPRGLILHG³5XOHRI1LQHV´LVXVHGVHH
GLDJUDPEHORZ
·
LVWDNHQIURPWKHOHJVDQGDGGHGWRWKHKHDGRIDFKLOG\HDUROG)RUHDFK
VXEVHTXHQW\HDULVUHWXUQHGWRWKHOHJVXQWLO\HDUVROGDWZKLFKWLPHWKHKHDGLVLQ
SURSRUWLRQWRWKHDGXOW
·
%\\HDUVRIDJHWKHUHODWLYHSURSRUWLRQVDVVXPHWKHYDOXHVIRUDGXOW%6$DQGKHQFHWKH
DGXOWGLDJUDPFDQEHXVHGDVDUHIHUHQFHDWWKDWWLPH

,WLVSUHIHUDEOHWKDWWKHSDWLHQW¶VKHLJKWDQGZHLJKWEHPHDVXUHG
LQFPDQGNJKRZHYHULIQHHGHG

7RFRQYHUWLQFKHVLQWRFHQWLPHWHUVFPWKHIROORZLQJ
FRQYHUVLRQVKRXOGEHXVHG
LQFK FP

7RFRQYHUWSRXQGVOEVWRNLORJUDPVNJWKHIROORZLQJ
FRQYHUVLRQVKRXOGEHXVHG
OE NJ


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI







3DUW
\HDUFKLOG
ERG\
RIWRWDO
\HDUFKLOG
ERG\
RIWRWDO
\HDUFKLOG
ERG\
RIWRWDO
\HDUDGXOW
ERG\
RIWRWDO
$UP




+HDG




1HFN


/HJ




$QWHULRUWUXQN




3RVWHULRUWUXQN











&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



$33(1',;%(F]HPD$UHDDQG6HYHULW\,QGH[6FRUH($6,

7KH($6,LVDFRPSRVLWHVFRUHEDVHGRQWKHVHYHULW\RIIRXUGLIIHUHQWVLJQVRIDWRSLF
GHUPDWLWLVLQIRXUGLIIHUHQWDUHDVRIWKHERG\PXOWLSOLHGE\WKHSHUFHQWRIWKDWVSHFLILFERG\
DUHDDIIHFWHGPXOWLSOLHGE\DZHLJKWLQJIDFWRU

(U\WKHPD
 &OHDU



1RHYLGHQFHRIHU\WKHPD
 0LOG



'HILQLWHOLJKWUHGFRORUDWLRQ
 0RGHUDWH



0RGHUDWHUHGQHVVEXWQRWGDUN
 6HYHUH



'DUNUHGFRORUDWLRQ

,QGXUDWLRQSDSXODWLRQHGHPD 

 &OHDU



1RHYLGHQFHRIDQ\LQGXUDWLRQSDSXODWLRQHGHPD
 0LOG



%DUHO\SHUFHSWLEOHHOHYDWLRQ
 0RGHUDWH



&OHDUO\SHUFHSWLEOHHOHYDWLRQ
 6HYHUH



0DUNHGDQGH[WHQVLYHHOHYDWLRQ

/LFKHQLILFDWLRQ
 &OHDU



1RHYLGHQFHRIOLFKHQLILFDWLRQ
 0LOG
6OLJKWWKLFNHQLQJRIVNLQGLVFHULEOHRQO\E\WRXFK
DQGZLWKVNLQPDUNLQJVPLQLPDOO\H[DJJHUDWHG
 0RGHUDWH
'HILQLWHWKLFNHQLQJRIVNLQZLWKVNLQPDUNLQJ
H[DJJHUDWHGVRWKDWWKH\IRUPDYLVLEOHFULVVFURVV
RUULGJHGSDWWHUQ
 6HYHUH
7KLFNHQHGVNLQZLWKVNLQPDUNLQJVYLVLEO\
SRUWUD\LQJDQH[DJJHUDWHGFULVVFURVVRUULGJHG
SDWWHUQ

([FRULDWLRQ
 &OHDU
1RHYLGHQFHRIH[FRULDWLRQ
 0LOG
6FDQWHYLGHQFHRIH[FRULDWLRQZLWKQRVLJQVRI
GHHSHUVVNLQGDPDJHDEVHQFHRIHURVLRQRU
FUXVWV
 0RGHUDWH
6HYHUDOOLQHDUPDUNVRIVNLQZLWKVRPHVKRZLQJ
HYLGHQFHRIGHHSHUVNLQLQMXU\HURVLRQFUXVW
YLVLEOH
 6HYHUH
0DQ\HURVLYHRUFUXVW\OHVLRQVSUHVHQW




7KHSDWLHQWZLOOEHUHTXLUHGWRUDWHWKHVHYHULW\RIWKHLUSUXULWLVLWFKLQJVFUDWFKLQJGLVFRPIRUWRYHUWKH


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



SUHYLRXVKRXUVXVLQJWKHIROORZLQJVFDOH

3UXULWLV
 1RQH
1RQH
 0LOG
2FFDVLRQDOVOLJKWLWFKLQJRUVFUDWFKLQJ
 0RGHUDWH&RQVWDQWRULQWHUPLWWHQW
LWFKLQJVFUDWFKLQJGLVFRPIRUWZKLFKLVQRW
GLVWXUELQJVOHHS
 6HYHUH
%RWKHUVRPHLWFKLQJVFUDWFKLQJGLVFRPIRUW
ZKLFKLVGLVWXUELQJVOHHS

(F]HPDLQGXUDWLRQH[FRULDWLRQDQGOLFKHQLILFDWLRQDUHSDUWRIWKH($6,VFRUHEXWSUXULWLVLVQRW

($6,6FRUH

7KH($6,VFRUHLVFDOFXODWHGDVIROORZV
+HDGQHFN
(,;/[$UHD[LQFKLOGUHQDJHV[
8SSHU/LPEV
(,;/[$UHD[
7UXQN 
(,;/[$UHD[
/RZHU/LPEV
(,;/[$UHD[LQFKLOGUHQDJHV[
($6,6&25( 6802)$%29(5(*,216

(
(U\WKHPD
,
,QGXUDWLRQSDSXODWLRQHGHPD
;
([FRULDWLRQ
/
/LFKHQLILFDWLRQ

6HYHULW\LVEDVHGRQWKH,QYHVWLJDWRU¶VDVVHVVPHQWRILQGLYLGXDOVLJQVDQGV\PSWRPV
 QRQH PLOG PRGHUDWH VHYHUHXVLQJWKHGHILQLWLRQVDERYH

7KHRIHDFKERG\UHJLRQDIIHFWHGLVVFRUHGDVWKHYDULDEOH$UHDDERYHLQWKH($6,
IRUPXOD)RUWKHERG\UHJLRQVKHDGQHFNXSSHUOLPEVWUXQNDQGORZHUOLPEVLIWKH

$UHD 
LIDIIHFWHGLV
$UHD 
LIDIIHFWHGLVWR
$UHD 
LIDIIHFWHGLVWR
$UHD 
LIDIIHFWHGLVWR
$UHD 
LIDIIHFWHGLVWR
$UHD 
LIDIIHFWHGLVWR
$UHD 
LIDIIHFWHGLVWR

($6,6FRUHFDQEHSUHVHQWHGWRWKHQHDUHVWZKROHQXPEHUQRGHFLPDOVDQGDOOQXPEHUV
VKRXOGEHURXQGHGVKRXOGEHURXQGHGXSWRWKHQHDUHVWZKROHQXPEHU



&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



7KHPLQLPXPVFRUHZRXOGEHDQGWKH0D[LPXP6FRUHZRXOGEH7REHHOLJLEOHIRU
SDUWLFLSDWLRQLQWKLVVWXG\DSDWLHQWPXVWKDYHDQ($6,RIDWOHDVWDWEDVHOLQH









&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



$33(1',;&,QYHVWLJDWRU*OREDO$VVHVVPHQW,*$

7REHHOLJLEOHIRULQFOXVLRQLQWKHVWXG\WKH,*$PXVWEHRUDWEDVHOLQH7REH
FRQVLGHUHGD&OLQLFDO6XFFHVVWKHSDWLHQWPXVWVFRUHDDW9LVLW


&OHDU
0LQRUUHVLGXDOGLVFRORUDWLRQQRHU\WKHPDRULQGXUDWLRQSDSXODWLRQ
QRRR]LQJFUXVWLQJ

$OPRVW&OHDU
-XVWSHUFHSWLEOHHU\WKHPDZLWKDOPRVWQRLQGXUDWLRQSDSXODWLRQDQG
QRRR]LQJFUXVWLQJ

0LOG'LVHDVH
'HILQLWHSLQNHU\WKHPDZLWKPLOGLQGXUDWLRQSDSXODWLRQDQGQR
RR]LQJFUXVWLQJ

0RGHUDWH
'LVHDVH
5HGHU\WKHPDZLWKPRGHUDWHLQGXUDWLRQSDSXODWLRQDQGWKHUHPD\EH
VRPHRR]LQJFUXVWLQJ

6HYHUH'LVHDVH
'DUNEULJKWUHGHU\WKHPDZLWKVHYHUHLQGXUDWLRQSDSXODWLRQZLWK
RR]LQJFUXVWLQJ

























&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




$33(1',;'$SSOLFDWLRQ6LWH5HDFWLRQV

7KHIROORZLQJDSSOLFDWLRQVLWHUHDFWLRQVZLOOEHHYDOXDWHGDWHDFKYLVLWEDVHGRQWKHVFDOHSURYLGHGEHORZ
%XUQLQJ
(URVLRQ
(GHPD
3DLQ
,WFKLQJ
'U\QHVV

$EVHQW 

0LOG


VOLJKWEDUHO\SHUFHSWLEOH
0RGHUDWH

GLVWLQFWSUHVHQFH
6HYHUH 

PDUNHGLQWHQVH























&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI




$33(1',;(&RUWLVRO5HVSRQVH7HVW

7KLVFRUWLVROUHOHDVHWHVWLVPRGLILHGIURPWKHSURFHGXUHRI:RRGHWDODVGHVFULEHGLQWKH3URGXFW/DEHO
IRU&RUWURV\Q70FRV\QWURSLQIRULQMHFWLRQ$PSKVWDU3KDUPDFHXWLFDOV,QF
7KHSURFHGXUHLVDVIROORZV
 $VLQJOHPOEORRGVDPSOHVKRXOGEHWDNHQDVWKHEDVDOVDPSOH
 PJDVLQJOHYLDORI&RUWURV\Q70FRV\QWURSLQVKRXOGEHUHFRQVWLWXWHGZLWKPORI
VRGLXP FKORULGH LQMHFWLRQ 863 LQMHFWHG LQWUDPXVFXODUO\ ,Q SDWLHQWV XQGHU  \HDUV RI DJH
PJRI&RUWURV\Q70ZLOOEHXVHG
 PLQXWHVDIWHUWKH,0LQMHFWLRQDVHFRQGPOEORRGVDPSOHVKRXOGEHREWDLQHG7KHUHVXOWLQJ
WZRVHUXPVDPSOHVDWOHDVWPORIVHUXPLQHDFKVKRXOGEHSURFHVVHGDQGODEHOHGDFFRUGLQJWR
WKHLQVWUXFWLRQVSURYLGHGDQGVHQWWKHVDPHGD\WR$&0*OREDO/DERUDWRU\IRUDQDO\VLVRIEDVDO
DQGSRVWVWLPXODWHGVHUXPFRUWLVROFRQFHQWUDWLRQ

7KHUHVXOWLQJEORRGVDPSOHVVKRXOGEHVHQWWR$&0*OREDO/DERUDWRU\IRULPPHGLDWHWHVWLQJ
9LVLW7HVW
$FRUWLVROUHVSRQVHWHVWZLOOEHFRPSOHWHGDW9LVLW
9LVLW7HVW
7KHWHVWDWWKH(QGRI6WXG\YLVLWVKRXOGQRWEHSHUIRUPHGLIWKHSDWLHQWGRVHGZLWKLQKRXUV
$SDWLHQWZLOOEHFRQVLGHUHGWRKDYHQRUPDOEDVDOFRUWLVROOHYHODQGDGUHQDOIXQFWLRQLIWKH\PHHWDOOWKUHH
FULWHULDOLVWHGEHORZXQGHU1RUPDO)DLOXUHWRPHHWDQ\RIWKHVHFULWHULDLVLQGLFDWLYHRIDEQRUPDODGUHQDO
IXQFWLRQRUSRWHQWLDO+3$D[LVVXSSUHVVLRQ


&RUWLVRO5HVXOWV
1RUPDO
$EQRUPDO
%DVDO
SUH&RUWURV\Q70
LQMHFWLRQ
PFJPO
PFJPO
PLQXWHVSRVW
&RUWURV\Q70LQMHFWLRQ
EDVDOYDOXH
EDVDOYDOXH
!PFJPO
PFJPO

+3$$[LVVXSSUHVVLRQZLOOEHGHILQHGDVDPLQXWHSRVW&RUWURV\Q70LQMHFWLRQOHYHOFRUWLVROOHYHO
RIPFJPO$VWKHVWXG\WUHDWPHQWSHULRGZLOOEHRYHUDQ\SDWLHQWVZLWKUHVXOWVRI+3$D[LV
VXSSUHVVLRQZLOOEHDGYLVHGQRWWRLQLWLDWHDQ\QHZVWHURLGWKHUDS\WRSLFDORURWKHUZLVHDQGWRUHWXUQ
WRWKHVLWHLQGD\VDWZKLFKWLPHWKH\ZLOOEHDVVHVVHGIRU+3$D[LVVXSSUHVVLRQ
$Q\SDWLHQWSUHVHQWLQJZLWKV\PSWRPVRI+3$D[LVVXSSUHVVLRQVXFKDVQDXVHDKHDGDFKHP\DOJLD
IDWLJXH RU ORRVH VWRRO ZLOO EH UHIHUUHG WR DQ HQGRFULQRORJLVW $V DQ DGGLWLRQDO VDIHW\ SUHFDXWLRQ
ZULVWEDQGVLGHQWLI\LQJWKHSDWLHQWDVVRPHRQHVXIIHULQJIURPDGUHQDOVXSSUHVVLRQVHFRQGDU\WRVWHURLG
ZLWKGUDZDOZLOOEHSURYLGHGWRDOHUWPHGLFDOSHUVRQQHOVKRXOGDQ\HPHUJHQFLHVDULVHEHIRUHDGUHQDO
IXQFWLRQUHWXUQVWRQRUPDO
,I WKH UHVXOWV RI WKH FRUWLVRO UHVSRQVH WHVW VWLOO VKRZ VLJQV RI +3$ D[LV VXSSUHVVLRQ  GD\V DIWHU
GLVFRQWLQXLQJ WKHUDS\ WKH\ ZLOO EHDVNHG WR UHWXUQ LQ  GD\V  GD\V DIWHU GLVFRQWLQXLQJ VWHURLG
WKHUDS\IRUDQRWKHUIROORZXSWHVW,IWKHSDWLHQWLVVWLOOVKRZLQJVLJQVRI+3$D[LVVXSSUHVVLRQ


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



GD\VDIWHUGLVFRQWLQXLQJVWHURLGWKHUDS\DQGSUHVHQWVZLWKUHODWHGV\PSWRPVWKH\ZLOOEHUHIHUUHGWR
DQHQGRFULQRORJLVW
,I+3$D[LVVXSSUHVVLRQSHUVLVWVIRUGD\VDIWHUGLVFRQWLQXLQJVWHURLGWKHUDS\EXWWKHSDWLHQWKDVQR
V\PSWRPVWKH\ZLOOEHDVNHGWRUHWXUQLQGD\VGD\VDIWHUGLVFRQWLQXLQJVWHURLGWKHUDS\IRU
DQRWKHU IROORZXS WHVW ,I +3$ D[LV VXSSUHVVLRQ SHUVLVWV IRU  GD\V DIWHU GLVFRQWLQXLQJ VWHURLG
WKHUDS\SDWLHQWVZLOOEHUHIHUUHGWRDQHQGRFULQRORJLVWUHJDUGOHVVRIV\PSWRPV
3DWLHQWV VKRXOG QRW EH VXEMHFWHG WR &RUWURV\Q70 WHVWLQJ RU DQ\ RWKHU FKDOOHQJH WR WKHLU DGUHQDO
UHVSRQVHDQ\VRRQHUWKDQZHHNVIURPWKHLUODVW&RUWURV\Q70WHVW

)ROORZ8S6FKHGXOHIRU3DWLHQWVVKRZLQJVLJQVRI+3$$[LV6XSSUHVVLRQ
'D\V
DIWHUGF
+3$5HVXOWV
6\PSWRP
V
3DWLHQW&RXUVH

1RUPDO
1$
6WXG\RYHU

$EQRUPDO
<HV
5HIHUWRHQGRFULQRORJLVW

$EQRUPDO
1R
5HSHDWWHVWLQGD\V

1RUPDO
1$
6WXG\RYHU

$EQRUPDO
<HV
5HIHUWRHQGRFULQRORJLVW

$EQRUPDO
1R
5HSHDWWHVWLQGD\V

1RUPDO
1$
6WXG\RYHU

$EQRUPDO
<HVRU1R
5HIHUWRDQHQGRFULQRORJLVW






&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



$33(1',;)(YDOXDWLRQRI+3$$[LV6XSSUHVVLRQ
&RUWLFRVWHURLG(IIHFWRQ+3$$[LV)HHGEDFN/RRS



$VVHVVPHQWRI&RUWLFRVWHURLG(IIHFWRQ+3$$[LV)HHGEDFN/RRS




























7KH +\SRWKDODPXV VHFUHWHV &RUWLFRWURSKLQ
5HOHDVLQJ+RUPRQH&5+ZKLFKWULJJHUVWKH
DQWHULRU
SLWXLWDU\
WR
UHOHDVH
$GUHQRFRUWLFRWURSKLQ
+RUPRQH
$&7+
$&7+VWLPXODWHVWKHDGUHQDOFRUWH[WRUHOHDVH
JOXFRFRUWLFRVWHURLGV LQWR WKH EORRGVWUHDP
,QFUHDVHGOHYHOVRIFLUFXODWLQJJOXFRFRUWLFRLGV
LQ WKH EORRGVWUHDP VHQG D VLJQDO WR WKH
K\SRWKDODPXV WR GHFUHDVH WKH VHFUHWLRQ RI
&5+ DQG DOVR WR WKH DQWHULRU SLWXLWDU\ WR
GHFUHDVHWKHVHFUHWLRQRI$&7+UHVXOWLQJLQD
GHFUHDVH LQ FLUFXODWLQJ JOXFRFRUWLFRVWHURLGV
([RJHQRXV FRUWLFRVWHURLGV LQFOXGLQJ WKRVH
DEVRUEHGV\VWHPLFDOO\WKURXJKWKHVNLQPD\
DOVR LPSDUW D PHVVDJH WR WKH K\SRWKDODPXV
DQGDQWHULRUSLWXLWDU\WRGHFUHDVHVHFUHWLRQRI
KRUPRQHV  7KLV PD\ UHVXOW LQ GHFUHDVHG
FLUFXODWLQJ JOXFRFRUWLFRVWHURLGV DQG WKXV D
GHFUHDVHGUHVSRQVHWRJOXFRFRUWLFRVWHURLGV
/RZFLUFXODWLQJFRUWLVROOHYHOVRUDGHFUHDVHG
UHVSRQVH WR FRUWLVRO DUH LQGLFDWLYH RI
VXSSUHVVLRQ RIWKHDFWLYLW\ RI WKH +3$ D[LV
,QRUGHUWRHYDOXDWHWKH+3$D[LVIXQFWLRQRI
SDWLHQWVLQWKLVVWXG\EDVDOOHYHOVRIFRUWLVRO
LQ WKH EORRG ZLOO EH PHDVXUHG DW WKH HQG RI
WUHDWPHQW3DWLHQWVZLOOWKHQEHLQMHFWHGZLWK
&RUWRV\Q70 D V\QWKHWLF VXEXQLW RI $&7+
6\VWHPLF DGPLQLVWUDWLRQ RI D V\QWKHWLF
VXEXQLWRI$&7+VKRXOGVWLPXODWHWKH
$GUHQDO
&RUWH[
WR
UHOHDVH
JOXFRFRUWLFRVWHURLGVXQOHVVWKHSDWLHQWKDV
KDG   LQFUHDVHG   FLUFXODWLQJ OHYHOV RI
JOXFRFRUWLFRVWHURLGV IRU VRPH WLPH DQG WKH
+3$D[LVKDVEHHQVXSSUHVVHG$IWHU
 PLQXWHV KDYH  SDVVHG  EORRG  OHYHOV  RI
FRUWLVRO ZLOO EH PHDVXUHGDJDLQ /DFN RI RU
OLPLWHGUHOHDVHRIJOXFRFRUWLFRVWHURLGVLQWR
WKH EORRG VWUHDP LQ UHVSRQVH WR WKH
DGPLQLVWHUHG
&RUWRV\Q70
ZLOO
LQGLFDWH
VXSSUHVVLRQRI+3$D[LVIXQFWLRQ


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



$33(1',;*&OLQLFDO/DERUDWRU\7HVWLQJ
$VSDUWRIWKH6FUHHQLQJ3URFHGXUHVDQGDW9LVLWRUHDUO\WHUPLQDWLRQIRUUDQGRPL]HGSDWLHQWVRQO\
SDWLHQWVZLOOKDYHDEORRGVDPSOHWDNHQIRUKHPDWRORJ\DQGFOLQLFDOFKHPLVWU\WHVWLQJ7KHWHVWLQJSDQHO
VKRXOGLQFOXGHDVDPLQLPXPWKHIROORZLQJWHVWV
+HPDWRORJ\
·
+HPDWRFULW
·
:KLWHEORRGFHOOFRXQW
·
3ODWHOHWV
·
+HPRJORELQ
·
5HGEORRGFHOOFRXQW
·
'LIIHUHQWLDOZKLWHFHOOFRXQW
&KHPLVWU\
·
$ONDOLQHSKRVSKDWDVH
·
7RWDOELOLUXELQ
·
$ODQLQHWUDQVDPLQDVH
·
&UHDWLQLQH
·
$VSDUWDWHWUDQVDPLQDVH
·
*OXFRVH
·
%ORRGXUHDQLWURJHQ
&OLQLFDO/DERUDWRU\7HVWLQJZLOOEHSHUIRUPHGDWD&HQWUDO/DERUDWRU\
$&00HGLFDO/DE,QF
(OPJURYH3DUN
5RFKHVWHU1<86$


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



$33(1',;+&RUWURV\Q3DFNDJH,QVHUW
FOR DIAGNOSTIC USE ONLY
CORTROSYN
TM
(cosyntropin) for Injection
DESCRIPTION
&257526<170 FRV\QWURSLQ IRU ,QMHFWLRQ LV D VWHULOH ,\RSKLOL]HG SRZGHU LQ YLDOV FRQWDLQLQJ  PJ RI &257526<170 DQG  PJ RI PDQQLWRO WR EH
UHFRQVWLWXWHGZLWKP/RI6RGLXP&KORULGH,QMHFWLRQ863$GPLQLVWUDWLRQLVE\LQWUDYHQRXVRULQWUDPXVFXODULQMHFWLRQ&RV\QWURSLQLVĮFRUWLFRWURSLQD
V\QWKHWLFVXEXQLWRI$&7+,WLVDQRSHQFKDLQSRO\SHSWLGHFRQWDLQLQJIURPWKH1WHUPLQXVWKHILUVWRIWKHDPLQRDFLGVRIQDWXUDO$&7+7KHVHTXHQFHRI
DPLQRDFLGVLQWKHFRPSRXQGLVDVIROORZV
CLINICAL PHARMACOLOGY
&257526<170FRV\QWURSLQIRU,QMHFWLRQH[KLELWVWKHIXOOFRUWLFRVWHURLGRJHQLFDFWLYLW\RIQDWXUDO$&7+9DULRXVVWXGLHVKDYHVKRZQWKDWWKHELRORJLFDFWLYLW\RI
$&7+UHVLGHVLQWKH1WHUPLQDOSRUWLRQRIWKHPROHFXOHDQGWKDWWKHDPLQRDFLGUHVLGXHLVWKHPLQLPDOVHTXHQFHUHWDLQLQJIXOODFWLYLW\3DUWLDORUFRPSOHWH
ORVVRIDFWLYLW\LVQRWHGZLWKSURJUHVVLYHVKRUWHQLQJRIWKHFKDLQEH\RQGDPLQRDFLGUHVLGXHV)RUH[DPSOHWKHGHFUHPHQWIURPWRUHVXOWVLQDORVVRI
SRWHQF\
7KH SKDUPDFRORJLF SURILOH RI &257526<170 LV VLPLODU WR WKDW RI SXULILHG QDWXUDO $&7+ ,W KDV EHHQ HVWDEOLVKHG WKDW  PJ RI &257526<170 ZLOO
VWLPXODWHWKHDGUHQDOFRUWH[PD[LPDOO\DQGWRWKHVDPHH[WHQWDVXQLWVRIQDWXUDO$&7+7KLVGRVHRI&257526<170ZLOOSURGXFHPD[LPDOVHFUHWLRQRI
2+FRUWLFRVWHURLGVNHWRVWHURLGVDQGRUNHWRJHQLFVWHURLGV
7KH H[WUDDGUHQDO HIIHFWV ZKLFK QDWXUDO $&7+ DQG &257526<170 KDYH LQ FRPPRQ LQFOXGH LQFUHDVHG PHODQRWURSLF DFWLYLW\ LQFUHDVHG JURZWK KRUPRQH
VHFUHWLRQDQGDQDGLSRNLQHWLFHIIHFW7KHVHDUHFRQVLGHUHGWREHZLWKRXWSK\VLRORJLFDORUFOLQLFDOVLJQLILFDQFH
$QLPDOKXPDQDQGV\QWKHWLF$&7+ZKLFKDOOFRQWDLQDPLQRDFLGVH[KLELWVLPLODULPPXQRORJLFDFWLYLW\7KLVDFWLYLW\UHVLGHVLQWKH&WHUPLQDOSRUWLRQRIWKH
PROHFXOHDQGWKHDPLQRDFLGUHVLGXHVH[KLELWWKHJUHDWHVWGHJUHHRIDQWLJHQLFLW\,QFRQWUDVWV\QWKHWLFSRO\SHSWLGHVFRQWDLQLQJRUIHZHUDPLQRDFLGV
KDYHQRGHWHFWDEOHLPPXQRORJLFDFWLYLW\7KRVHFRQWDLQLQJRUDPLQRDFLGVKDYHYHU\OLWWOHLPPXQRORJLFDOWKRXJKIXOOELRORJLFDFWLYLW\7KLVSURSHUW\
RI&257526<170DVVXPHVDGGHGLPSRUWDQFHLQYLHZRIWKHNQRZQDQWLJHQLFLW\RIQDWXUDO$&7+
INDICATIONS AND USAGE
&257526<170FRV\QWURSLQIRU,QMHFWLRQLVLQWHQGHGIRUXVHDVDGLDJQRVWLFDJHQWLQWKHVFUHHQLQJRISDWLHQWVSUHVXPHGWRKDYHDGUHQRFRUWLFDOLQVXIILFLHQF\
%HFDXVHRILWVUDSLGHIIHFWRQWKHDGUHQDOFRUWH[LWPD\EHXWLOL]HGWRSHUIRUPDPLQXWHWHVWRIDGUHQDOIXQFWLRQSODVPDFRUWLVROUHVSRQVHDVDQRIILFHRU
RXWSDWLHQWSURFHGXUHXVLQJRQO\YHQLSXQFWXUHVVHH'26$*($1'$'0,1,675$7,21VHFWLRQ
6HYHUHK\SRIXQFWLRQRIWKHSLWXLWDU\DGUHQDOD[LVLVXVXDOO\DVVRFLDWHGZLWKVXEQRUPDOSODVPDFRUWLVROYDOXHVEXWDORZEDVDOOHYHOLVQRWSHUVHHYLGHQFHRI
DGUHQDOLQVXIILFLHQF\DQGGRHVQRWVXIILFHWRPDNHWKHGLDJQRVLV0DQ\SDWLHQWVZLWKSURYHQLQVXIILFLHQF\ZLOOKDYHQRUPDOEDVDOOHYHOVDQGZLOOGHYHORSVLJQVRI
LQVXIILFLHQF\RQO\ZKHQVWUHVVHG)RUWKLVUHDVRQDFULWHULRQZKLFKVKRXOGEHXVHGLQHVWDEOLVKLQJWKHGLDJQRVLVLVWKHIDLOXUHWRUHVSRQGWRDGHTXDWHFRUWLFRWURSLQ
VWLPXODWLRQ:KHQSUHVXPSWLYHDGUHQDOLQVXIILFLHQF\LVGLDJQRVHGE\DVXEQRUPDO&257526<170WHVWIXUWKHUVWXGLHVDUHLQGLFDWHGWRGHWHUPLQHLILWLVSULPDU\
RUVHFRQGDU\
3ULPDU\ DGUHQDO LQVXIILFLHQF\ $GGLVRQ¶V GLVHDVH LV WKH UHVXOW RI DQ LQWULQVLF GLVHDVH SURFHVV VXFK DV WXEHUFXORVLV ZLWKLQ WKH JODQG 7KH SURGXFWLRQ RI
DGUHQRFRUWLFDO KRUPRQHV LV GHILFLHQW GHVSLWH KLJK $&7+ OHYHOV IHHGEDFN PHFKDQLVP 6HFRQGDU\ RU UHODWLYH LQVXIILFLHQF\ DULVHV DV WKH UHVXOW RI GHIHFWLYH
SURGXFWLRQRI$&7+OHDGLQJLQWXUQWRGLVXVHDWURSK\RIWKHDGUHQDOFRUWH[,WLVFRPPRQO\VHHQIRUH[DPSOHDVUHVXOWRIFRUWLFRVWHURLGWKHUDS\6KHHKDQ¶V
V\QGURPHDQGSLWXLWDU\WXPRUVRUDEODWLRQ
7KHGLIIHUHQWLDWLRQRIERWKW\SHVLVEDVHGRQWKHSUHPLVHWKDWDSULPDULO\GHIHFWLYHJODQGFDQQRWEHVWLPXODWHGE\$&7+ZKHUHDVDVHFRQGDULO\GHIHFWLYHJODQGLV
SRWHQWLDOO\IXQFWLRQDODQGZLOOUHVSRQGWRDGHTXDWHVWLPXODWLRQZLWK$&7+3DWLHQWVVHOHFWHGIRUIXUWKHUVWXG\DVWKHUHVXOWRIDVXEQRUPDO&257526<170WHVW
VKRXOGEHJLYHQDRUGD\FRXUVHRIWUHDWPHQWZLWK5HSRVLWRU\&RUWLFRWURSLQ,QMHFWLRQ863DQGWKHQUHWHVWHG6XJJHVWHGGRVHVDUH863XQLWVWZLFHGDLO\IRU
GD\VRU863XQLWVWZLFHGDLO\IRUGD\V8QGHUWKHVHFRQGLWLRQVOLWWOHRUQRLQFUHDVHLQSODVPDFRUWLVROOHYHOVZLOOEHVHHQLQ$GGLVRQ¶VGLVHDVHZKHUHDV
KLJKHURUHYHQQRUPDOOHYHOVZLOOEHVHHQLQFDVHVZLWKVHFRQGDU\DGUHQDOLQVXIILFLHQF\
CONTRAINDICATION
7KHRQO\FRQWUDLQGLFDWLRQWR&257526<170FRV\QWURSLQIRU,QMHFWLRQLVDKLVWRU\RIDSUHYLRXVDGYHUVHUHDFWLRQWRLW

PRECAUTIONS


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



General
&257526<170FRV\QWURSLQIRU,QMHFWLRQH[KLELWVVOLJKWLPPXQRORJLFDFWLYLW\GRHVQRWFRQWDLQDQLPDOSURWHLQDQGLVWKHUHIRUHOHVVULVN\WRXVHWKDQQDWXUDO
$&7+3DWLHQWVNQRZQWREHVHQVLWL]HGWRQDWXUDO$&7+ZLWKPDUNHGO\SRVLWLYHVNLQWHVWVZLOOZLWKIHZH[FHSWLRQVUHDFWQHJDWLYHO\ZKHQWHVWHGLQWUDGHUPDOO\ZLWK
&257526<170 0RVW SDWLHQWV ZLWK D KLVWRU\ RI D SUHYLRXV K\SHUVHQVLWLYLW\ UHDFWLRQ WR QDWXUDO $&7+ RU D SUHH[LVWLQJ DOOHUJLF GLVHDVH ZLOO WROHUDWH
&257526<170 'HVSLWH WKLV KRZHYHU &257526<170 LV QRW FRPSOHWHO\ GHYRLG RI LPPXQRORJLF DFWLYLW\ DQG K\SHUVHQVLWLYLW\ UHDFWLRQV LQFOXGLQJ UDUH
DQDSK\OD[LVDUHSRVVLEOH7KHUHIRUHWKHSK\VLFLDQVKRXOGEHSUHSDUHGSULRUWRLQMHFWLRQWRWUHDWDQ\SRVVLEOHDFXWHK\SHUVHQVLWLYLW\UHDFWLRQ
Drug Interactions
&RUWLFRWURSLQPD\DFFHQWXDWHWKHHOHFWURO\WHORVVDVVRFLDWHGZLWKGLXUHWLFWKHUDS\
Carcinogenesis, Mutagenesis, Impairment of Fertility
/RQJWHUPVWXGLHVLQDQLPDOVKDYHQRWEHHQSHUIRUPHGWRHYDOXDWHFDUFLQRJHQLFRUPXWDJHQLFSRWHQWLDORULPSDLUPHQWRIIHUWLOLW\$VWXG\LQUDWVQRWHGLQKLELWLRQRI
UHSURGXFWLYHIXQFWLRQOLNHQDWXUDO$&7+
Pregnancy
3UHJQDQF\&DWHJRU\&$QLPDOUHSURGXFWLRQVWXGLHVKDYHQRWEHHQFRQGXFWHGZLWK&257526<170FRV\QWURSLQIRU,QMHFWLRQ,WLVDOVRQRWNQRZQZKHWKHU
&257526<170FDQFDXVHIHWDOKDUPZKHQDGPLQLVWHUHGWRDSUHJQDQWZRPDQRUFDQDIIHFWUHSURGXFWLRQFDSDFLW\&257526<170VKRXOGEHJLYHQWRD
SUHJQDQWZRPDQRQO\LIFOHDUO\QHHGHG
Nursing Mothers
,W LV QRW NQRZQ ZKHWKHU WKLV GUXJ LV H[FUHWHG LQ KXPDQ PLON %HFDXVH PDQ\ GUXJV DUH H[FUHWHG LQ KXPDQ PLON FDXWLRQ VKRXOG EH H[HUFLVHG ZKHQ
&257526<170FRV\QWURSLQIRU,QMHFWLRQLVDGPLQLVWHUHGWRDQXUVLQJZRPDQ
Pediatric Use
6HH'26$*($1'$'0,1,675$7,21VHFWLRQ
ADVERSE REACTIONS
6LQFH &257526<170 FRV\QWURSLQ IRU ,QMHFWLRQ LV LQWHQGHG IRU GLDJQRVWLF DQG QRW WKHUDSHXWLF XVH DGYHUVH UHDFWLRQV RWKHU WKDQ D UDUH K\SHUVHQVLWLYLW\
UHDFWLRQDUHQRWDQWLFLSDWHG$UDUHK\SHUVHQVLWLYLW\UHDFWLRQXVXDOO\DVVRFLDWHGZLWKDSUHH[LVWLQJDOOHUJLFGLVHDVHDQGRUDSUHYLRXVUHDFWLRQWRQDWXUDO$&7+LV
SRVVLEOH6\PSWRPVPD\LQFOXGHVOLJKWZKHDOLQJZLWKVSORWFK\HU\WKHPDDWWKHLQMHFWLRQVLWH7KHUHKDYHEHHQUDUHUHSRUWVRIDQDSK\ODFWLFUHDFWLRQ7KHIROORZLQJ
DGYHUVHUHDFWLRQVKDYHEHHQUHSRUWHGLQSDWLHQWVDIWHUWKHDGPLQLVWUDWLRQRI&257526<170DQGWKHDVVRFLDWLRQKDVEHHQQHLWKHUFRQILUPHGQRUUHIXWHG
ƔEUDG\FDUGLD
ƔWDFK\FDUGLD
ƔK\SHUWHQVLRQ
ƔSHULSKHUDOHGHPD
ƔUDVK
DOSAGE AND ADMINISTRATION
&257526<170FRV\QWURSLQIRU,QMHFWLRQPD\EHDGPLQLVWHUHGLQWUDPXVFXODUO\RUDVDGLUHFWLQWUDYHQRXVLQMHFWLRQZKHQXVHGDVDUDSLGVFUHHQLQJWHVWRI
DGUHQDO IXQFWLRQ ,W PD\ DOVR EH JLYHQ DV DQ LQWUDYHQRXV LQIXVLRQ RYHU D  WR  KRXU SHULRG WR SURYLGH D JUHDWHU VWLPXOXV WR WKH DGUHQDO JODQGV 'RVHV RI
&257526<170WRPJKDYHEHHQXVHGLQFOLQLFDOVWXGLHVDQGDPD[LPDOUHVSRQVHQRWHGZLWKWKHVPDOOHVWGRVH

$VXJJHVWHGPHWKRGIRUDUDSLGVFUHHQLQJWHVWRIDGUHQDOIXQFWLRQ KDVEHHQGHVFULEHGE\:RRGDQG$VVRFLDWHV$FRQWUROEORRGVDPSOHRIWRP/LV
FROOHFWHGLQDKHSDULQL]HGWXEH5HFRQVWLWXWHPJRI&257526<170ZLWKP/RI6RGLXP&KORULGH,QMHFWLRQ863DQGLQMHFWLQWUDPXVFXODUO\7KH
UHFRQVWLWXWHGGUXJSURGXFWVKRXOGEHLQVSHFWHGYLVXDOO\IRUSDUWLFXODWHPDWWHUDQGGLVFRORUDWLRQSULRUWRLQMHFWLRQ5HFRQVWLWXWHG&257526<170VKRXOGQRWEH
UHWDLQHG,QWKHSHGLDWULFSRSXODWLRQDJHG\HDUVRUOHVVDGRVHRIPJZLOORIWHQVXIILFH$VHFRQGEORRGVDPSOHLVFROOHFWHGH[DFWO\PLQXWHVODWHU%RWK
EORRGVDPSOHVVKRXOGEHUHIULJHUDWHGXQWLOVHQWWRWKHODERUDWRU\IRUGHWHUPLQDWLRQRIWKHSODVPDFRUWLVROUHVSRQVHE\VRPHDSSURSULDWHPHWKRG,ILWLVQRWSRVVLEOH
WRVHQGWKHPWRWKHODERUDWRU\RUSHUIRUPWKHIOXRULPHWULFSURFHGXUHZLWKLQKRXUVWKHQWKHSODVPDVKRXOGEHVHSDUDWHGDQGUHIULJHUDWHGRUIUR]HQDFFRUGLQJWR
QHHG

7ZRDOWHUQDWLYHPHWKRGVRIDGPLQLVWUDWLRQDUHLQWUDYHQRXVLQMHFWLRQDQGLQIXVLRQ&257526<170FDQEHLQMHFWHGLQWUDYHQRXVO\LQWRP/RIVDOLQHRYHUD
PLQXWH SHULRG :KHQ JLYHQ DV DQ LQWUDYHQRXV LQIXVLRQ &257526<170  PJ PD\ EH DGGHG WR JOXFRVH RU VDOLQH VROXWLRQV DQG JLYHQ DW WKH UDWH RI


&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



DSSUR[LPDWHO\PLFURJUDPVSHUKRXURYHUDKRXUSHULRG,WVKRXOGQRWEHDGGHGWREORRGRUSODVPDDVLWLVDSWWREHLQDFWLYDWHGE\HQ]\PHV$GUHQDOUHVSRQVH
PD\EHPHDVXUHGLQWKHXVXDOPDQQHUE\GHWHUPLQLQJXULQDU\VWHURLGH[FUHWLRQEHIRUHDQGDIWHUWUHDWPHQWRUE\PHDVXULQJSODVPDFRUWLVROOHYHOVEHIRUHDQGDWWKH
HQGRIWKHLQIXVLRQ7KHODWWHULVSUHIHUDEOHEHFDXVHWKHXULQDU\VWHURLGH[FUHWLRQGRHVQRWDOZD\VDFFXUDWHO\UHIOHFWWKHDGUHQDORUSODVPDFRUWLVROUHVSRQVHWR
$&7+

7KHXVXDOQRUPDOUHVSRQVHLQPRVWFDVHVLVDQDSSUR[LPDWHGRXEOLQJRIWKHEDVDOOHYHOSURYLGHGWKDWWKHEDVDOOHYHOGRHVQRWH[FHHGWKHQRUPDOUDQJH3DWLHQWV
UHFHLYLQJFRUWLVRQHK\GURFRUWLVRQHRUVSLURQRODFWRQHVKRXOGRPLWWKHLUSUHWHVWGRVHVRQWKHGD\VHOHFWHGIRUWHVWLQJ3DWLHQWVWDNLQJLQDGYHUWHQWGRVHVRIFRUWLVRQH
RUK\GURFRUWLVRQHRQWKHWHVWGD\DQGSDWLHQWVWDNLQJVSLURQRODFWRQHRUZRPHQWDNLQJGUXJVZKLFKFRQWDLQHVWURJHQPD\H[KLELWDEQRUPDOO\KLJKEDVDOSODVPD
FRUWLVROOHYHOV
$SDUDGR[LFDOUHVSRQVHPD\EHQRWHGLQWKHFRUWLVRQHRUK\GURFRUWLVRQHJURXSDVVHHQLQDGHFUHDVHLQSODVPDFRUWLVROYDOXHVIROORZLQJDVWLPXODWLQJGRVHRI
&257526<170
,QWKHVSLURQRODFWRQHRUHVWURJHQJURXS RQO\D QRUPDOLQFUHPHQWDOUHVSRQVHLVWREHH[SHFWHG0DQ\ SDWLHQWVZLWK QRUPDODGUHQDOIXQFWLRQ KRZHYHUGR QRW
UHVSRQGWRWKHH[SHFWHGGHJUHHVRWKDWWKHIROORZLQJFULWHULDKDYHEHHQHVWDEOLVKHGWRGHQRWHDQRUPDOUHVSRQVH

7KHFRQWUROSODVPDFRUWLVROOHYHOVKRXOGH[FHHGPLFURJUDPVP/
7KHPLQXWHOHYHOVKRXOGVKRZDQLQFUHPHQWRIDWOHDVWPLFURJUDPVP/DERYHWKHEDVDOOHYHO
7KHPLQXWHOHYHOVKRXOGH[FHHGPLFURJUDPVP/&RPSDUDEOHILJXUHVKDYHEHHQUHSRUWHGE\*UHLJDQGFRZRUNHUV

3ODVPDFRUWLVROOHYHOVXVXDOO\SHDNDERXWWRPLQXWHVDIWHUDQLQMHFWLRQRI&257526<170DQGVRPHSUHIHUWKHPLQXWHLQWHUYDOIRUWHVWLQJIRUWKLV
UHDVRQ:KLOHLWLVWUXHWKDWWKHPLQXWHYDOXHVDUHXVXDOO\KLJKHUWKDQWKHPLQXWHYDOXHVWKHGLIIHUHQFHPD\QRWEHVLJQLILFDQWHQRXJKLQPRVWFDVHVWR
RXWZHLJKWKHGLVDGYDQWDJHRIDORQJHUWHVWLQJSHULRG,IWKHPLQXWHWHVWSHULRGLVXVHGWKHFULWHULRQIRUDQRUPDOUHVSRQVHLVDQDSSUR[LPDWHGRXEOLQJRIWKH
EDVDOSODVPDFRUWLVROYDOXH

,QSDWLHQWVZLWKDUDLVHGSODVPDELOLUXELQRULQSDWLHQWVZKHUHWKHSODVPDFRQWDLQVIUHHKHPRJORELQIDOVHO\KLJKIOXRUHVFHQFHPHDVXUHPHQWVZLOOUHVXOW7KHWHVW
PD\EHSHUIRUPHGDWDQ\WLPHGXULQJWKHGD\EXWEHFDXVHRIWKHSK\VLRORJLFDOGLXUQDOYDULDWLRQRISODVPDFRUWLVROWKHFULWHULDOLVWHGE\:RRGFDQQRWDSSO\,WKDV
EHHQVKRZQWKDWEDVDOSODVPDFRUWLVROOHYHOVDQGWKHSRVW&257526<170LQFUHPHQWH[KLELWGLXUQDOFKDQJHV+RZHYHUWKHPLQXWHSODVPDFRUWLVROOHYHO
UHPDLQVXQFKDQJHGWKURXJKRXWWKHGD\VRWKDWRQO\WKLVVLQJOHFULWHULRQVKRXOGEHXVHG

3DUHQWHUDO GUXJ SURGXFWV VKRXOG EH LQVSHFWHG YLVXDOO\ IRU SDUWLFXODWH PDWWHU DQG GLVFRORUDWLRQ ZKHQHYHU VROXWLRQ DQG FRQWDLQHU SHUPLW 5HFRQVWLWXWHG
&257526<170VKRXOGQRWEHUHWDLQHG
HOW SUPPLIED 
%R[RIYLDOVRI&257526<170FRV\QWURSLQIRU,QMHFWLRQPJ
1'&
Storage
6WRUHDW&)
&257526<170LVLQWHQGHGDVDVLQJOHGRVHLQMHFWLRQDQGFRQWDLQVQRDQWLPLFURELDOSUHVHUYDWLYH$Q\XQXVHGSRUWLRQVKRXOGEHGLVFDUGHG
Rx only
REFERENCES
:RRG-%HWDO/$1&(7
*UHLJ:5HWDO-(1'2&5
0F*LOO3(HWDO$115+(80',6
Amphastar Pharmaceuticals, Inc.
5DQFKR&XFDPRQJD&$86$5(9






&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



$33(1',;,,QYHVWLJDWRU%URFKXUH'HVR[LPHWDVRQH7RSLFDO6SUD\





&21),'(17,$/35272&2/
$Q2SHQ/DEHO6DIHW\6WXG\WR$VVHVVWKH3RWHQWLDOIRU$GUHQDO6XSSUHVVLRQ)ROORZLQJ7UHDWPHQWZLWK
'HVR[LPHWDVRQH7RSLFDO6SUD\7DUR3KDUPDFHXWLFDOV86$,QFLQ3DWLHQWVZLWK$WRSLF'HUPDWLWLV


5HY¡6HSWHPEHU¡7DUR3KDUPDFHXWLFDOV86$,QF¡3DJHRI



$33(1',;-3URWRFRO5HYLVLRQV

5HYLVLRQ
5HYLVLRQ
1XPEHU
5HYLVLRQ'DWH
·
3URWRFRO5HYGDWHDGGHGWR7LWOHSDJHXSGDWHG
LQWKHIRRWHU
·
9ROXPHRIEORRGGUDZXSGDWHGLQ$SSHQGL['
·
&OHULFDOHUURUVFRUUHFWHGWKURXJKRXWWKH
GRFXPHQW
·
$SSHQGL[+3URWRFRO5HYLVLRQDGGHGWRWKH
GRFXPHQW




5HYLVLRQ
5HYLVLRQ
1XPEHU
5HYLVLRQ'DWH
·
$SSOLFDWLRQ6LWH5HDFWLRQV$SSHQGL['
DGGHGWRWKHSURWRFRO
·
&OHULFDOFRUUHFWLRQVWKURXJKRXWWKHGRFXPHQW
·
3URWRFRO5HYLVLRQ$SSHQGL[-XSGDWHG




SAP_000.pdf: 
NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
STATISTICAL ANALYSIS PLAN 
An Open Label, Safety Study to Assess the Potential for Adrenal Suppression Following 
Treatment with Desoximetasone 0.15% Topical Spray (Taro Pharmaceuticals U.S.A., Inc.) in 
Patients with Atopic Dermatitis 
0511912017 
Protocol Number: DSXS 1502a 
Novum Study Number: 71615002 
Sponsor: 
Taro Pharmaceuticals U.S.A., Inc. 
3 Skyline Drive, 
Hawthorne, NY 10532 
USA 
Contract Research Organization: 
Novum Pharmaceutical Research Services 
225 W. Station Square Drive, Suite 200 
Pittsburgh, P A 15219 
May 19,2017 
Final Version 1.0 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 1 of64 


NOVVM PHARMACEUTICAL RESEARCH SERVICES 
ST A TISTJCAL ANALYSIS PLAN 
Desoximetasoae &.15% Topical Spray 
Protoeol/ Study No. DSXS l50la /71615002 
· · SAP FINAL VERSION APPROVAUl 
An Open Label, Safety Study to Assess the Potential for Adrenal Suppression Following 
Treatment with Desoximetasone 0. I 5% Topical Spray (faro Phannaceuticals U.S.A., Inc.) 
in Patients with Atopic Dermatitis 
Written By: 
. 
Signature: ~ 
Date: 
o6[t3J~I1-
Jianhua Liu, MSc 
Senior Biostatistician 
Novum Pharmaceutical Research Services 
Revmv.dBy. ~·~ 
Date: 90(13/ )o ( =r 
Signature: 
. . · 
Pina D'Angelo, M 
. 
. 
Senior Director, Scientific Affairs (Biostatistics) 
Novum Pharmaceutical Research Services 
Approved By: Natalie 
~~b)' 
NlllloYai'IIO'I>Idy 
Yantovskiy 
o-2017.1l6.0i 
9 June 2017 
Signature: 
11l04:$0-o4'00' 
Date: 
" 
~·· .. , -·-
Natalie Yantovskiy 
Senior Director, Clinical Research 
Taro Phannaceuticals U.S.A., Inc. 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 2 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
Revision History 
VERSION 
DATE 
DESCRIPTiON OF REVISIONS 
REVISED. BY 
Draft 1.0 
January 19, 2017 
New Document 
Jianhua Liu 
Final 1.0 
May 19, 2017 
SAP finalization 
Jianhua Liu 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 3 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
List of Abbreviations and Definition of Terms 
ADaM 
AE 
BP 
BSA 
c 
CRF 
CDISC 
CRO 
EASI 
F 
FDA 
HR 
Hg 
HPA 
ICH 
IGA 
IND 
LOCF 
MedDRA 
ITT 
LOCF 
OGD 
pp 
SAE 
SAP 
SAS 
SDTM 
USA 
0511912017 
Analysis Data Model 
Adverse Event 
Blood Pressure 
Body Surface Area 
Celsius 
Case Report Form 
Clinical Data Interchange Standards Consortium 
Contract Research Organization 
Eczema Area and Severity Index 
Fahrenheit 
Food and Drug Administration 
Heart Rate 
Mercury 
Hypothalamic Pituitary Adrenal 
International Conference on Harmonisation 
Investigator's Global Assessment 
Investigational New Drug 
Last Observation Carried Forward 
Medical Dictionary for Regulatory Activities 
Intent-to-Treat 
Last Observation Carried Forward 
The Office of Generic Drugs 
Per-Protocol 
Serious Adverse Event 
Statistical Analysis Plan 
Statistical Analysis System 
Study Data Tabulation Model 
United States of America 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 4 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
TABLE OF CONTENTS 
1. INTRODUCTION ....................................................................................................................... 8 
2. OBJECTIVES .............................................................................................................................. 8 
3. OVERALL STUDY DESIGN ..................................................................................................... 8 
4. RANDOMIZATION AND BLINDING .................................................................................... 11 
5. SAMPLE SIZE .......................................................................................................................... 11 
6. STUDY ENDPOINTS ............................................................................................................... 11 
7. STATISTICAL ANALYSIS METHODS ................................................................................. 12 
7.1 Baseline Characteristics ...................................................................................................... 12 
7.1.1 Subject Disposition ..................................................................................................... 12 
7 .1.2 Demographic and Other Baseline Characteristics ....................................................... 12 
7.1.3 Medical History ........................................................................................................... 12 
7 .1.4 Concomitant Medications ........................................................................................... 13 
7.1.5 Pregnancy Test ............................................................................................................ 13 
7.2 Safety Analysis ofPotential HPA Axis Suppression .......................................................... 13 
7.3 Safety Analysis ................................................................................................................... 14 
7.3.1 Adverse Events ............................................................................................................ 14 
7.3.2 Vital Signs ................................................................................................................... 14 
7.3 .3 Laboratory Evaluations ............................................................................................... 14 
7.3.4 Investigator Global Assessment .................................................................................. 15 
7.3.5 Eczema Area and Severity Index Score (EASI) .......................................................... 15 
7.3.6 Percent BSA Affected ................................................................................................. 15 
7.3.7 Application Site Reaction ............................................................................................ 16 
7.3.8 Pruritus Assessment .................................................................................................... 16 
7.4 Multiple Comparisons ......................................................................................................... 16 
7.5 Methods for Handling Missing Data ................................................................................... 16 
7.6 Interim Analyses ................................................................................................................. 16 
7.7 Changes to the Planned Analyses ....................................................................................... 16 
8. TABLE, LISTING AND FIGURE SHELLS ............................................................................ 16 
T16.1.9.1 Summary ofEnrolled Patients .................................................................................. 19 
T16.1.9.2 Summary ofProtocol Deviations (Safety Population) ............................................ 20 
T16.1.9.3 Summary ofDemographic Data (Safety Population) .............................................. 21 
T16.1.9.4 Summary of Patients Randomized, Included in Safety Analysis ofPotential 
HPA Axis Suppression by Study Center ........................................................................... 23 
T16.1.9.5 Summary ofFrequency ofHPA Axis Suppression at the End ofTreatment 
(Day 28) ............................................................................................................................. 24 
T16.1.9.5a Summary of Logistic Regression Analysis Results ofHPA Axis 
Suppression at the End of Treatment (Day 28) .................................................................. 25 
T16.1.9.6 Summary ofPercent BSA Affected with Atopic Dermatitis (Safety 
Population) ......................................................................................................................... 26 
T16.1.9.7 Summary of Frequency oflnvestigator Global Assessment (IGA) (Safety 
Population) ......................................................................................................................... 27 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 5 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.8 Summary of Total Score- Eczema Area and Severity Index (EASI) (Safety 
Population) ......................................................................................................................... 28 
T16.1.9.9 Overall Summary of Adverse Events (Safety Population) ...................................... .29 
T16.1.9.10.1 Summary of Frequency of All Adverse Events by Body System (Safety 
Population) ........................................................................................................................ .30 
T16.1.9.10.2 Summary of Frequency of All Adverse Events in~ 2% of Patients by 
Body System (Safety Population) ..................................................................................... 30 
T16.1.9.11 Summary of Frequency of All Adverse Events by Severity (Safety 
Population) ......................................................................................................................... 31 
T16.1.9.12 Summary ofFrequency of All Adverse Events by Relationship (Safety 
Population) ......................................................................................................................... 32 
T16.1.9.13 Summary ofFrequency of Serious Adverse Events (Safety Population) .............. .33 
T 16.1.9 .14 Summary of Shift Analysis of Clinical Laboratory Assessments 
(Chemistry) from Baseline to Day 28 (Safety Population) ............................................... .34 
T16.1.9.15 Summary of Shift Analysis of Clinical Laboratory Assessments 
(Hematology) from Baseline to Day 28 (Safety Population) ............................................. 34 
T16.1.9.16 Summary of Frequency ofPruritis Assessment (Safety Population) .................... 35 
T16.1.9.17 Summary of Application Site Reaction (Safety Population) .................................. 36 
L16.2.1 Listing ofDiscontinued Patients ................................................................................. .37 
L16.2.2 Listing ofProtocol Deviations ..................................................................................... 38 
L16.2.3 Patients Excluded from Safety Analysis of Potential HPA Axis Suppression ............ 39 
L16.2.4.1 Listing ofDemographic Data .................................................................................. .40 
L 16.2.4.2 Listing of Medical History ...................................................................................... .41 
L16.2.4.3 Listing of Concomitant Medication ......................................................................... .42 
L16.2.5.1 Listing of Drug Administration ............................................................................... .43 
L16.2.5.2 Listing of Study Medication Weight ....................................................................... .44 
L 16.2.6.1 Listing of Cortisol Response Test Results ............................................................... .45 
L16.2.6.2 Listing ofHPA Axis Suppression Follow-Up ......................................................... .46 
L16.2.6.3 Listing oflnvestigator Global Assessment (IGA) ................................................... .47 
L 16.2.6.4 Listing of Percent BSA Affected with Atopic Dermatitis ....................................... .48 
L16.2.6.5 Listing of Eczema Area and Severity Index (EASI) ............................................... .49 
L16.2.6.6 Listing ofPruritis Assessment .................................................................................. 50 
L16.2.6.7 Listing of Application Site Reaction ........................................................................ 51 
L 16.2. 7 Listing of Adverse Events by Cohort .......................................................................... 52 
L16.2.8.1 Listing ofPositive Pregnancy Test Results .............................................................. 53 
L16.2.8.2 Listing of Abnormal Vital Signs .............................................................................. 54 
L16.2.8.3 Listing of Abnormal Physical Examination Results ................................................. 55 
L 16.2.8.4 Listing of Clinical Hematology Laboratory Results ................................................. 56 
L 16.2.8.5 Listing of Clinical Chemistry Laboratory Results .................................................... 57 
10. APPENDICES , ........................................................................................................................ 58 
APPENDIX A: Body Surface Area Calculation ...................................................................... 58 
APPENDIX B: Eczema Area and Severity Index Score (EASI) ............................................. 60 
APPENDIX C: Investigator Global Assessment (IGA) ........................................................... 62 
05/1912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 6 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
APPENDIX D: Cortisol Response Test ................................................................................... 63 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 7 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the final Clinical Study Protocol DSXS 1502a 
(Novum Study No. 71615002) Rev. 2 dated 09/0612016. The SAP provides details on the 
planned statistical methodology for the analysis of the study data. The SAP also outlines the 
statistical programming specifications for the tables, listings and figures. 
This SAP describes the study endpoints, derived variables, anticipated data transformations and 
manipulations, and other details of the analyses not provided in the study protocol. This SAP 
therefore outlines in detail all other aspects pertaining to the planned analyses and 
presentations for this study. 
The following documents were reviewed in preparation of this SAP: 
• 
Final Clinical Study Protocol DSXS 1502a (Novum Study No. 71615002) Rev. 2 dated 
09/06/2016 
• 
Case Report Form Version 1.0 for Novum Study No. 71615002 
The reader of this SAP is encouraged to also read the clinical protocol for details on the 
conduct of this study, and the operational aspects of clinical assessments and timing for 
completing a patient in this study. 
2. OBJECTIVES 
1. The objective of this study is to evaluate the potential of desoximetasone 0.15% topical 
spray to suppress HP A axis function in patients with moderate to severe atopic 
dermatitis. 
2. The secondary objectives are to evaluate to evaluate the efficacy parameters and 
adverse event (AE) profiles of desoximetasone 0.15% topical spray administered to 
patients with moderate to severe atopic dermatitis. 
3. OVERALL STUDY DESIGN 
This open label, safety study is designed to evaluate the potential for adrenal suppression after 
treatment with desoximetasone 0.15% topical spray (Taro Pharmaceuticals, U.S.A.), for the 
treatment of moderate to severe atopic dermatitis. 
Approximately 25 to 50 eligible patients with atopic dermatitis that satisfY all eligibility criteria 
will be enrolled into the study at Visit 1. Patients must be overall in good health. They should 
have a current diagnosis of moderate to severe atopic dermatitis with IGA score of at least 3 or 4. 
Approximately twenty-four (25) to fifty (50) patients stratified by age with a confirmed 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 8 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
diagnosis of moderate to severe atopic dermatitis with: 
Cohort 1 - 10 -20 patients age 12-17 years of age with 10-30% body surface area (BSA) 
affected 
Cohort 2- 5-10 patients age 6-11 years of age with 10-30% body surface area (BSA) 
affected 
Cohort 3- 5-10 patients age 2-5 years of age with 10-30% body surface area (BSA) affected 
Cohort 4- 5-10patients 6 months to 1 year of age with 10-30% body surface area (BSA) 
affected 
Cohorts will be enrolled in sequential order. Each cohort will initiate enrollment once the 
previous cohort has reached the minimum number of patients and a safety analysis has been 
reviewed. Each cohort will be enrolled based on the availability of patients. 
Each cohort will be reviewed for the potential ofHPA axis suppression. If at least 50% of 
patients in a Cohort experience HPA axis suppression, enrollment for that cohort will be stopped 
and no further cohorts will be initiated. If at least 35% of patients have experienced HPA axis 
suppression across all cohorts combined during the study, enrollment will be discontinued and no 
other cohorts will be initiated. Cohort 2 will not begin until safety data has been reviewed for 
Cohort 1. The same process will be followed for each Cohort until the study is complete. 
The enrollment in the individual Cohort may not be required if the satisfactory safety data for the 
same age group was obtained in the study DSXS 1502. 
Patients enrolled in the study will apply product twice a day, according to provided instructions, 
for a total of 28 days. 
Patients will attend a total of 3 Clinic Visits as follows: 
• 
Visit 1 (Day 1): Screening/Enrollment 
• 
Visit 2 (Day 14±2): Interim Visit 
• 
Visit 3 (Day 29±2): End of Study or Early Termination 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 9 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
Figure 1 Study Schematic 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Day 
1 
14±2 
29±2 
42±4 
Enrollment 
Interim 
End of Study/Early 
Telephone 
Procedures 
Before 12 
Visit 
Termination 
Follow-Up 
pm 
Before 12 pm 
Visit 
Informed Consent 
X 
Medical History and 
X 
Demographics 
Vital Signs 
X 
X 
X 
Pregnancy Test* 
X 
X 
X 
Physical Exam 
X 
X 
% BSA Assessment 
X 
X 
X 
IGA Score 
X 
X 
X 
EASI Score 
X 
X 
X 
Application Site Reactions 
X 
X 
X 
Concomitant Medication 
X 
X 
X 
Laboratory Evaluations 
X 
X 
Cortisol Response Test 
X 
X 
Confirm Inclusion/Exclusion 
X 
Criteria 
Dispense Sunscreen and 
X 
Wristband 
Weigh and Dispense Study 
X 
X 
Drug 
Collect and Weigh Study Drug 
X 
X 
Dispense/Review Patient Diary 
X 
X 
X 
Adverse Events 
X 
X 
X 
Evaluation of Patient 
X 
X 
Compliance to the Protocol 
* Pregnancy test will be earned out for females of chtldbeanng potenttal. 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 10 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
4. RANDOMIZATION AND BLINDING 
Patients eligible for enrollment into the study will fall into one of four cohorts: 
Cohort 1-10-20 patients age 12-17 years of age with 10-30% body surface area (BSA) 
affected 
Cohort 2- 5-10 patients age 6-11 years of age with 10-30% body surface area (BSA) 
affected 
Cohort 3 -5-10 patients age 2-5 years of age with 10-30% body surface area (BSA) affected 
Cohort 4- 5-10 patients 6 months -1 year of age with 10-30% body surface area (BSA) 
affected 
At Visit 1 eligible patients will be enrolled to the study and assigned a patient number. 
Cohorts will be enrolled in sequential order. Each cohort will initiate enrollment once the 
previous cohort has reached the required number of patients and a safety analysis has been 
reviewed. Each cohort will be enrolled based on the availability of patients. 
Each cohort will be reviewed for the potential of HPA axis suppression. If at least 50% of 
patients in each Cohort experience HPA axis suppression, enrollment for that cohort will be 
stopped and no further cohorts will be initiated. If at least 35% of patients have experienced 
HPA axis suppression across cohorts combined during the study, enrollment will be discontinued 
and no other cohorts will be initiated. Cohort 2 will not begin until safety data has been 
reviewed for Cohort 1. The same process will be followed for each Cohort until the study is 
complete. 
The enrollment in the individual Cohort may not be required ifthe satisfactory safety data for the 
same age group was obtained in the study DSXS 1502. 
5. SAMPLE SIZE 
The sample size of35 patients, stratified by age and% BSA, was determined to be sufficient. 
6. STUDY ENDPOINTS 
Primary Outcome Measures: 
Hypothalamic Pituitary Adrenal (HPA) Axis Response to Cosyntropin demonstrating the absence 
or presence of adrenal suppression at the end of treatment 
05/1912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 11 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
Secondary Outcome Measures: 
Hypothalamic Pituitary Adrenal (HPA) Axis Response to Cosyntropin demonstrating the 
presence of adrenal suppression at the end of treatment with% BSA as a covariate. 
7. STATISTICAL ANALYSIS METHODS 
If not otherwise specified, statistical significance is defined as p<0.05 and is two-tailed. Data 
will be summarized with respect to demographic and baseline characteristics and safety 
variables. 
For categorical variables, the number and percent of each category within a parameter will be 
calculated for non-missing data. For continuous variables, statistics will include n, mean, standard 
deviation, median, minimum and maximum values. 
All statistical analyses will be conducted using SAS®, Version 9.4 or higher. Datasets will be prepared 
using headings from Clinical Data Interchange Consortium (CDISC) Study Data Tabulation Model 
(SDTM) implementation for human clinical trials and ADaM (Analysis Dataset Model). 
7.1 Baseline Characteristics 
7.1.1 Subject Disposition 
The subject accountability and disposition information will be summarized by study cohort. The 
number of subjects enrolled, treated with study medication will be tabulated by study cohort. In 
addition, completion status and primary reason for withdrawal will be summarized by study cohort. 
7.1.2 Demographic and Other Baseline Characteristics 
The cohorts will be compared for basic demographics (age, gender, ethnicity and race), baseline 
IGA, baseline EASI and baseline total BSA. 
Summary tables by cohort will be presented. Continuous variables will be summarized using 
descriptive statistics (n, mean, standard deviation, median, minimum, maximum). Categorical 
variables will be summarized using frequencies and percentage. 
Baseline comparability of the four cohorts will be presented using Chi-square test for the 
categorical variables, and Analysis of Variance for the continuous variables. 
All data will be listed by cohort and patient. 
7.1.3 Medical History 
At Visit 1, patients will be questioned about medical history, including acute and chronic 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 12 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
medical history and medical history relevant to their atopic dermatitis. 
Medical history data will be listed by cohort and patient. 
7.1.4 Concomitant Medications 
At Visits 1-3, patients will be questioned about current and concomitant medication over the past 
12 weeks. 
All prior and concomitant medications taken since screening until the end of the study will be 
listed by cohort and patient. 
7.1.5 Pregnancy Test 
Urine pregnancy tests on women of child-bearing potential will be performed at Visits 1, 2, and 
3. 
Positive pregnancy test results will be listed by cohort and patient. 
7.2 Safety Analysis of Potential HPA Axis Suppression 
Dosing will be twice a day for 28 days excluding the doses prior to the Cortisol Response Test 
(54 applications). All patients who are enrolled, use at least 42 doses of the study drug and have 
data from a post-treatment cortisol response test will be included in the analysis. Patients who 
have not used 42 doses ofthe study drug will be excluded from the primary analysis ofHPA axis 
suppression. 
The primary analysis of interest is the proportion of patients in each group who are considered to 
have demonstrated possible HPA axis suppression following treatment with the study 
medication. As a secondary analysis ofthe data a logistic regression of the proportion of patients 
in the study with HPA axis suppression may be performed with %BSA affected as a covariate. 
This will depend on the distribution of the %BSA data collected. 
The study will be enrolled by Cohort starting with Cohort 1 and each cohort will be reviewed for 
the potential of HPA axis suppression. If at least 50% of patients in Cohort 1 experience HPA 
axis suppression once the minimum number of patients has been enrolled and completed the 
cohort, enrollment for that cohort will be stopped and no further cohorts will be initiated. If at 
least 35% of patients have experienced HPA axis suppression across cohorts combined during 
the study, enrollment will be discontinued and no other cohorts will be initiated. Cohort 2 will 
not begin until safety data has been reviewed for Cohort 1. The same process will be followed 
for each Cohort until the study is complete. 
For all patients the actual amount of desoximetasone (mg) applied during the study will be 
05/1912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 13 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
calculated from recorded bottle weights and presented. 
7.3 Safety Analysis 
Safety analysis will be conducted on all patients who applied at least one dose of study drug. 
7.3.1 Adverse Events 
All the adverse events (AEs) reported throughout the study will be coded and classified 
according to the MedDRA (Medical Dictionary for Regulatory Activities) coding dictionary 
(Version 19 or higher). Each adverse event is to be evaluated for date of start and end, 
seriousness, severity, causal relationship with the study drugs, action taken and outcome. 
A summary table of the number and percent of patients with AEs by system organ class, 
preferred term, and cohort will be presented. Each patient will be counted only once within each 
preferred term. 
A frequency summary table of the number of AEs by system organ class, preferred term, 
severity, and cohort will be presented. Severity will be classified as "Mild", "Moderate", or 
"Severe". 
Similarly, a frequency summary table of the number of AEs by system organ class, preferred 
term, and relationship to a study drug, and cohort will be presented. Relationship to a study drug 
will be classified as "Not Related" or "Related" where "Related" includes "Possible", 
"Probable", or "Definite". 
Should sufficient data exist, adverse event frequencies will be compared between cohorts using 
Fisher's exact test. 
All AEs will be listed by cohort and patient. 
7 .3.2 Vital Signs 
The patient's vital signs will be recorded (heart rate, blood pressure, temperature and respiration 
rate) at Visit 1, 2, and 3. 
Abnormal vital signs will be listed by cohort and patient. 
7.3.3 Laboratory Evaluations 
At Visit 1 and Visit 3 a blood sample will be collected for hematology and clinical chemistry 
testing. The testing panel should include as a minimum the following tests: 
Hematology 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 14 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
• 
Hematocrit 
• 
White blood cell count 
• 
Platelets 
• 
Hemoglobin 
• 
Red blood cell count 
• 
Differential white cell count 
Chemistry 
• 
Alkaline phosphatase 
• 
Total bilirubin 
• 
Alanine transaminase 
• 
Creatinine 
• 
Aspartate transaminase 
• 
Glucose 
• 
Blood urea nitrogen 
Shift analysis using the categories; below, above and within the laboratory normal range will be 
performed to identify any specific laboratory parameter that shows a trend toward potentially 
clinically significant changes. 
All data will be listed by cohort and patient. 
7.3.4 Investigator Global Assessment 
At each visit the Investigator will perform an Investigator Global Assessment (IGA). 
Investigator Global Assessment will be summarized using frequency and percentage by cohort 
and visit. 
Investigator Global Assessment will also be listed by cohort and patient. 
7.3.5 Eczema Area and Severity Index Score (EASI) 
Eczema Area and Severity Index Score will be assessed at each visit. 
EASI will be summarized using frequency and percentage by cohort and visit. EASI will also be 
listed by cohort and patient. 
7.3.6 Percent BSA Affected 
The% BSA recorded at Visit 1, 2, and 3 will be summarized descriptively by cohort and visit. 
All data will be listed by cohort and patient. 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 15 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
7.3.7 Application Site Reaction 
A frequency summary table comparing application site reaction for each cohort will be presented 
by visit. 
All data will be listed by cohort and patient. 
7.3.8 Pruritus Assessment 
A frequency summary table comparing the severity of pruritus for each cohort will be presented 
by visit. 
All data will be listed by cohort and patient. 
7.4 Multiple Comparisons 
No multiple comparison adjustment will be made in this study. 
7.5 Methods for Handling Missing Data 
For demographic and baseline characteristics, each variable will be analyzed using all available 
data. Patients with missing data will be excluded only from analyses for which data are not 
available. 
7.6 Interim Analyses 
There is no interim analysis planned in this study. 
7.7 Changes to the Planned Analyses 
Protocol Section 10.1.3 states as a secondary analysis ofthe data a logistic regression ofthe 
proportion of patients in the study with HPA axis suppression will be performed with %BSA 
affected as a covariate. The following will be applied during the analyses. 
As a secondary analysis of the data a logistic regression of the proportion of patients in the study 
with HPA axis suppression may be performed with %BSA affected as a covariate. This will 
depend on the distribution of the %BSA data collected. 
8. TABLE, LISTING AND FIGURE SHELLS 
The following shells are provided in order to provide a framework for the display of data from 
this study. These shells may not be reflective of every aspect of this study but are intended to 
show the general layout ofthe Tables, Listings and Figures that will be included in the final 
05/1912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 16 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
clinical study report. Tables, Listings and Figures are numbered following the ICH structure. 
Table headers, variables names and footnotes will be modified as needed following data 
analyses. All descriptive and inferential statistical analyses will be performed using SAS® 
statistical software Version 9.4 or higher, unless otherwise noted. 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 17 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
05119/2017 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
TABLE, LISTING AND FIGURE SHELLS 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 18 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Patients 
Screened 
Randomized 
Completed Study 
Terminated Early 
Adverse Event 
Enrolled in error 
Lack of efficacy 
Lost to follow-up 
etc. 
Other 
Created on: ddmmmyy hh:mm 
05119/2017 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.1 Summary of Enrolled Patients 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Total 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
Page 1 ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 19 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.2 Summary of Protocol Deviations 
(Safety Population) 
Total Patients with Protocol Deviations 
Total Deviations 
Enrolled in Error 
Lost to Follow-up 
Missed Visit 
Non-compliance with study drug 
Outside Visit Window 
Restricted Medication Use 
etc 
Other 
Cohort 1 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
Cohort 2 
Cohort 3 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
Created on: ddmmmyy hh:mm 
05119/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Cohort 4 
Total 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
Page 1 ofN 
Page 20 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Novum Pharmaceutical Research Services 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.3 Summary of Demographic Data 
(Safety Population) 
Cohort 1 
Cohort 2 
Cohort3 
Cohort 4 
Total 
N=xx 
N=xx 
N=xx 
N=xx 
N=xx 
P-value 
Age (years) 
n 
XX 
XX 
XX 
XX 
XX 
x.xxxx 
Mean±SD 
xx.x± x.x 
xx.x± x.x 
xx.x ± x.x 
xx.x± x.x 
xx.x±x.x 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Range 
XX-XX 
XX-XX 
XX-XX 
XX-XX 
XX-XX 
Age Groups 
<=1 
-
-
xx (xx.x%) 
2-5 
-
xx (xx.x%) 
6-11 
-
xx (xx.x%) 
12-17 
xx (xx.x%) 
18-40 
41-64 
65-75 
> 75 
Race 
American Indian or Alaska Native 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
x.xxxx 
Asian 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Black/ African American 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Native Hawaiian or other Pacific 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Islander 
White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Ethnicity 
Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
x.xxxx 
Not Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
N= number of patients in the cohort; n= number of patients with data available;% is based on N 
Created on: ddmmmyy hh:mm 
Page 1 of 1 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 21 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Baseline Total BSA 
n 
Mean± SD 
Median 
Range 
Baseline IGA 
Clear 
Almost Clear 
Mild 
Moderate 
Severe 
EASI 
n 
Mean± SD 
Median 
Range 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.3 Summary of Demographic Data 
(Safety Population) 
Cohort 1 
Cohort 2 
Cohort3 
Cohort 4 
Total 
N=xx 
N=xx 
N=xx 
N=xx 
N=xx 
P-value 
XX 
XX 
XX 
XX 
XX 
x.xxxx 
xx.x± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x± x.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
XX-XX 
XX-XX 
XX-XX 
XX-XX 
XX-XX 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
x.xxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
XX 
XX 
XX 
XX 
XX 
x.xxxx 
xx.x± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x± x.x 
xx.x± x.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
XX-XX 
XX-XX 
XX-XX 
XX-XX 
XX-XX 
N= number of patients in the cohort; n= number of patients with data available;% is based on N 
Created on: ddmmmyy hh:mm 
Page 1 of2 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 22 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.4 Summary of Patients Randomized, Included in Safety Analysis of Potential HPA Axis Suppression by Study Center 
Total 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Site 
PI Name 
No. 
Rando-
Rando-
Rando-
Rando-
Rando-
. d 
Included 
Included 
Included 
Included 
Included 
miZe 
mized 
mized 
mized 
mized 
All 
-
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xxxx 
XX 
xx (xx.x%) 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xxxx 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
XX 
xx(xx.x%) 
Created on: ddmmmyy hh:mm 
Page 1 ofN 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 23 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.5 Summary ofFrequency ofHPA Axis Suppression at the End of Treatment (Day 28) 
All 
Cohort 1 
Cohort 2 
Cohort3 
Cohort 4 
HPAAxis 
N=xx 
Suppression 
N=xx 
N=xx 
N=xx 
N=xx 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Created on: ddmmmyy hh:mm 
Page 1 ofN 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 24 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.5a Summary of Logistic Regression Analysis Results ofHPA Axis Suppression at the End of Treatment (Day 28) 
95% Wald 
Wald 
Odds Ratio 
P-value 
Confidence Limits 
Chi-Square 
Cohort 1 vs. Cohort 2 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 1 vs. Cohort 3 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 1 vs. Cohort 4 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 2 vs. Cohort 3 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 2 vs. Cohort 4 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 3 vs. Cohort 4 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Baseline % BSA affected 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Created on: ddmmmyy hh:mm 
Page 1 ofN 
05/1912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 25 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.6 Summary of Percent BSA Affected with Atopic Dermatitis 
(Safety Population) 
Visit 
Statistic 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
(N = xx) 
(N = xx) 
(N = xx) 
(N = xx) 
n 
XX 
XX 
XX 
XX 
Mean± SD 
xxx.x ± xxx.x 
xxx.x ± xxx.x 
xxx.x ±x xx.x 
xxx.x ± xxx.x 
Median 
xxx.x 
xxx.x 
xxx.x 
XXX. X 
Range 
xxx.x - xxx.x 
xxx.x - xxx.x 
xxx.x - xxx.x 
xxx.x - xxx.x 
2 
3 
Created on: ddmmmyy hh:mm 
Page 1 ofN 
05119/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 26 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.7 Summary of Frequency oflnvestigator Global Assessment (IGA) 
(Safety Population) 
Score 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Visit 
(N = xx) 
(N = xx) 
(N = xx) 
(N = xx) 
0 (Clear) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
1 (Almost Clear) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2 (Mild Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
3 (Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Disease) 
4 (Severe Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2 
0 (Clear) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
I (Almost Clear) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2 (Mild Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
3 (Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Disease) 
4 (Severe Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
3 
Created on: ddmmmyy hh:mm 
Page I ofN 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 27 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.8 Summary of Total Score- Eczema Area and Severity Index (EASI) 
(Safety Population) 
Visit 
Statistic 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
(N = xx) 
(N = xx) 
(N = xx) 
(N = xx) 
n 
XX 
XX 
XX 
XX 
Mean± SD 
xxx.x± xx.x 
xxx.x ± xx.x 
xxx.x± xx.x 
xxx.x± xx.x 
Median 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Range 
XXX- XXX 
XXX-XXX 
XXX- XXX 
XXX- XXX 
2 
3 
Created on: ddmmmyy hh:mm 
Page 1 ofN 
05/1912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 28 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
Description 
Patients Randomized 
T16.1.9.9 Overall Summary of Adverse Events 
(Safety Population) 
Cohort 1 
Cohort 2 
Cohort 3 
N=xx 
N=xx 
N=xx 
XXX 
XXX 
XXX 
Patients with at least one AE 
Discontinued study drug due to above AE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
AEs reported 
Mild 
Moderate 
Severe 
Not Related 
Related 
Death 
Serious AE 
Related= Possible, Probable, Definite 
Created on: ddmmmyy hh:mm 
0511912017 
XXX 
XXX 
XXX 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
• Taro Pharmaceuticals U.S.A., Inc. • 
Cohort 4 
Total 
N=xx 
N=xx 
XXX 
XXX 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
XXX 
XXX 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Page I ofN 
Page 29 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.10.1 Summary of Frequency of All Adverse Events by Body System 
(Safety Population) 
Body System 
MedORA Term 
Cohort 
Patients with at least one AE 
Total 
Cohort I (N=xx) 
Cohort 2 (N=xx) 
Cohort 3 (N=xx) 
Cohort 4 (N=xx) 
Ear and labyrinth disorders 
Ear pain 
Cohort 1 (N=xx) 
Cohort 2 (N=xx) 
Cohort 3 (N=xx) 
Cohort 4 (N=xx) 
N =Total number of patient in each cohort; Percentage is based on total number of patients. 
Created on: ddmmmyy hh:mm 
Events 
Patients 
XX 
xx (xx.x%) 
XX 
xx (xx.x%) 
XX 
xx (xx.x%) 
XX 
xx (xx.x%) 
XX 
xx (xx.x%) 
XX 
xx (xx.x%) 
XX 
xx (xx.x%) 
XX 
xx (xx.x%) 
Fisher's 
p-value 
x.xxxx 
x.xxxx 
Page 1 ofN 
T16.1.9.10.2 Summary of Frequency of All Adverse Events in~ 2% of Patients by Body System 
(Safety Population) 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 30 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.11 Summary of Frequency of All Adverse Events by Severity 
(Safety Population) 
Body System 
MedORA Term 
Cohort 
Mild 
Moderate 
Patients with at least one AE 
Total 
Cohort 1 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
Cohort 2 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
Cohort 3 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
Cohort 4 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
Ear and labyrinth disorders 
Ear pain 
Cohort 1 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
Cohort 2 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
Cohort 3 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
Cohort 4 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
N =Total number of events in each cohort; Percentage is based on total number of events. 
Created on: ddmmmyy hh:mm 
05119/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Page 1 ofN 
Page 31 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.12 Summary of Frequency of All Adverse Events by Relationship 
(Safety Population) 
Body System 
MedDRA Term 
Cohort 
Patients with at least one AE 
Total 
Cohort I (N=xx) 
Cohort 2 (N=xx) 
Cohort 3 (N=xx) 
Cohort 4 (N=xx) 
Ear and labyrinth disorders 
Ear pain 
Cohort 1 (N=xx) 
Cohort 2 (N=xx) 
Cohort 3 (N=xx) 
Cohort 4 (N=xx) 
N =Total number of events in each cohort; Percentage is based on total number of events. 
Related= Possible, Probable, Definite 
Created on: ddmmmyy hh:mm 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Related 
Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Page 1 ofN 
Page 32 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.13 Summary of Frequency of Serious Adverse Events 
(Safety Population) 
Body System 
MedDRA 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Term 
N=xx 
N=xx 
N=xx 
N=xx 
Injury, poisoning and procedural 
Alcohol 
complications 
poisoning 
XX 
XX 
XX 
XX 
Created on: ddmmmyy hh:mm 
Page 1 ofN 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 33 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.14 Summary of Shift Analysis of Clinical Laboratory Assessments (Chemistry) from Baseline to Day 28 
(Safety Population) 
Alanine Aminotransferase (U/L) 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
Baseline-> 
Endpoint 
Low 
Normal 
High 
Low 
Normal 
High 
Low 
Normal 
High 
Low 
Normal High 
Low 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
(xx.x%) 
(xx.x%) 
(xx.x%) (xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) (xx.x%) (xx.x%) 
Normal 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
(xx.x%) 
(xx.x%) 
(xx.x%) (xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) (xx.x%) (xx.x%) 
High 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
(xx.x%) 
(xx.x%) 
(xx.x%) (xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) 
(xx.x%) (xx.x%) (xx.x%) 
Table will continue for other lab parameters. 
Similar table will be created for Tl6.1.9.18. 
T16.1.9.15 Summary of Shift Analysis of Clinical Laboratory Assessments (Hematology) from Baseline to Day 28 
(Safety Population) 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 34 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.16 Summary of Frequency ofPruritis Assessment 
(Safety Population) 
Score 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
(N = xx) 
(N = xx) 
(N = xx) 
(N = xx) 
Visit 
None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2 
None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
3 
Created on: ddmmmyy hh:mm 
Page 1 ofN 
05119/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 35 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
05119/2017 
Sign I Symptom 
Burning 
Erosion 
Erosion 
Edema 
Pain 
Itching 
Dryness 
Visit 
1 
2 
3 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
T16.1.9.17 Summary of Application Site Reaction 
(Safety Population) 
Cohort 1 
Cohort 2 
Cohort3 
Cohort 4 
Statistic 
(N = xx) 
(N = xx) 
(N = xx) 
(N = xx) 
Absent 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
Mild 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
Moderate 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
Severe 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
xxx (xx.x%) 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 36 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Created on: ddmmmyy hh:mm 
05119/2017 
Cohort 
Cohort 1 
Cohort2 
Cohort 3 
Cohort4 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.1 Listing of Discontinued Patients 
Patient 
Discontinuation 
Number 
Reason 
xx-xxxx 
Withdrawal by Subject 
xx-xxxx 
Lost to Follow-up 
Page 1 ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 37 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Cohort 
Cohort I 
Cohort 2 
Cohort 3 
Cohort 4 
Created on: ddmmmyy hh:mm 
05/19/2017 
L16.2.2 Listing of Protocol Deviations 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
Patient 
Number 
Event Description 
xx-xxxx 
Outside Visit Window (Visit 3) 
Page I ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 38 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.3 Patients Excluded from Safety Analysis of Potential HPA Axis Suppression 
Cohort 
Cohort I 
Cohort 2 
Cohort 3 
Cohort 4 
Created on: ddmmmyy hh:mm 
05/1912017 
Patient 
Number 
xx-xxxx 
Exclusion Reason 
Patient has not used 42 doses of the study drug 
Page I ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 39 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Cohort 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Patient 
Number 
xx-xxxx 
Created on: ddmmmyy hh:mm 
05/19/2017 
Age 
11 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.4.1 Listing of Demographic Data 
Gender 
Ethnicity 
Race 
Female 
Not Hispanic or Latino 
Black or African American 
Page 1 ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 40 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Cohort 
Cohort I 
Cohort2 
Cohort 3 
Cohort 4 
Patient 
Number 
xx-xxxx 
Created on: ddmmmyy hh:mm 
0511912017 
L16.2.4.2 Listing of Medical History 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
System 
Diagnosis or 
Surgical 
Procedure 
Start Date 
End Date 
Ongoing 
Gynecologic 
Menopause 
yyyy-mm-dd 
yyyy-mm-dd 
Page I ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 41 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Cohort 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Patient 
Number 
xx-xxxx 
Created on: ddmmmyy hh:mm 
05/19/2017 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.4.3 Listing of Concomitant Medication 
Treatment 
Area 
No 
Medication 
Lisinopril 
Dosage 
Frequency Route 
20MG 
QD 
PO 
• Taro Pharmaceuticals U.S.A., Inc. • 
Start/End 
Date 
yyyy-mm-dd I 
yyyy-mm-dd 
Indication 
Hypertension 
Page 1 ofN 
Page 42 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
Cohort 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort4 
Note to programmer: 
L16.2.5.1 Listing of Drug Administration 
Patient 
Number 
xxxx 
Date of 
First Dose 
yyyy-mm-dd 
Date of 
Last Dose 
yyyy-mm-dd 
Total 
Compliance 
Doses Applied 
(%) 
XX 
xx.x 
Compliance= [Total number of applications] I [Planned number of applications] * 100%, where Planned number of applications is determined as 
follows: 
for subjects who completed the study successfully: 56 applications (28 days of twice daily dosing); 
for subjects who discontinued early: the minimum between 56 and [(Date of Discontinuation- Date of First Application)]. 
Created on: ddmmmyy hh:mm 
Page 1 ofN 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 43 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Cohort 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort4 
Patient 
Number 
xxxx 
Created on: ddmmmyy hh:mm 
05/19/2017 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.5.2 Listing of Study Medication Weight 
Bottle 1 
Bottle 2 
Total 
Weight 
Weight 
Amount 
Date 
Date 
Dispensed 
Dispensed 
Collected 
Collected 
Applied 
{g} 
{g} 
(g) 
yyyy-mm-dd 
XX 
yyyy-mm-dd 
XX 
XXX 
Page 1 ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 44 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.6.1 Listing of Cortisol Response Test Results 
Cohort 1 
Basal 
Post Injection 
Was a Cortisol 
Post-
Cortisol 
Cortisol 
Have 
Have 
Patient 
Response Test 
Basal 
Injection Injection 
Concentration Concentration Abnormal HPAAxis 
Number 
Visit 
Date 
Sample 
Time 
Draw 
Level 
Level 
Adrenal Suppression 
conducted? 
Draw Time 
Time 
{mcg/lOOml} 
{mcg/lOOml} 
Function? 
? 
xx-xxxx 
I 
Yes 
yyyy-mm-dd 
hh:mm 
hh:mm 
hh:mm 
XXX 
XXX 
No 
3 
Yes 
yyyy-mm-dd 
hh:mm 
hh:mm 
hh:mm 
XXX 
XXX 
No 
Table will continue for other cohorts. 
Created on: ddmmmyy hh:mm 
Page I ofN 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 45 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.6.2 Listing ofHPA Axis Suppression Follow-Up 
Cohort 1 
Patient 
Number 
xx-xxxx 
Is The Patient Showing Signs 
Or Symptoms OfHPA Axis 
Suppression?/ 
Was a Cortisol Response 
Test Conducted? 
Yes/ Yes 
Date/ 
Basal Sample Draw Time/ 
Follow-Up Injection Time/ 
Test 
Post-Injection Draw Time 
Test I 
yyyy-mm-dd I hh:mm I 
hh:mml hh:mm 
Table will continue for other cohorts. 
Created on: ddmmmyy hh:mm 
Basal 
Cortisol 
Post Injection 
Cortisol 
Still Show 
Was the 
Concentration Concentration 
Signs of 
Patient Referred 
Level 
Level 
HP A Axis 
to an 
(mcg/lOOml) 
(mcg/lOOml) Suppression? Endocrinologist 
xxx 
xxx 
No 
No 
Page I ofN 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 46 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.6.3 Listing of Investigator Global Assessment (IGA) 
Cohort 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort4 
Created on: ddmmmyy hh:mm 
0511912017 
Patient 
Number 
xx-xxxx 
Visit 1 
0 
Visit 2 
0 
• Taro Pharmaceuticals U.S.A., Inc. • 
Visit 3 I Early 
Termination 
0 
Page I ofN 
Page 47 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.6.4 Listing of Percent BSA Affected with Atopic Dermatitis 
Cohort 
Cohort I 
Cohort 2 
Cohort 3 
Cohort4 
Created on: ddmmmyy hh:mm 
0511912017 
Patient 
Number 
xx-xxxx 
Visit 1 
Visit 2 
XXX 
XXX 
Visit 4 I Early 
Termination 
XXX 
• Taro Pharmaceuticals U.S.A., Inc. • 
Baseline Total 
BSA (m"2) 
X. XX 
Page I ofN 
Page 48 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.6.5 Listing of Eczema Area and Severity Index (EASI) 
Cohort 
Cohort I 
Cohort 2 
Cohort 3 
Cohort 4 
Patient 
Number 
xx-xxxx 
Created on: ddmmmyy hh:mm 
05/19/2017 
Visit 
I 
2 
3 
Erythema Induration, 
Location 
Papulation, Lichenification 
Edema 
Head/Neck 
0 
0 
0 
Upper Limbs 
0 
0 
0 
Trunk 
I 
I 
I 
Lower Limbs 
0 
0 
0 
• Taro Pharmaceuticals U.S.A., Inc. • 
Total 
Excoriation 
Total 
EASI 
Grade 
Score 
0 
0 
xxxx 
0 
0 
I 
4 
0 
0 
Page I ofN 
Page 49 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Cohort 
Cohort 1 
Cohort2 
Cohort 3 
Cohort4 
Created on: ddmmmyy hh:mm 
0511912017 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.6.6 Listing ofPruritis Assessment 
Patient 
Number 
xx-xxxx 
Visit 1 
0 (None) 
Visit2 
1 (Mild) 
• Taro Pharmaceuticals U.S.A., Inc. • 
Visit 3/Early 
Termination 
1 (Mild) 
Page 1 ofN 
Page 50 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Cohort 
Cohort 1 
Cohort2 
Cohort 3 
Cohort 4 
Patient 
Number 
xx-xxxx 
Created on: ddmmmyy hh:mm 
0511912017 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.6.7 Listing of Application Site Reaction 
Visit 
2 
3 
Burning 
0 
0 
0 
Sign I Symptom 
Erosion Edema 
Pain 
0 
0 
0 
0 
0 
0 
• Taro Pharmaceuticals U.S.A., Inc. • 
Itching 
Dryness 
0 
0 
0 
0 
0 
0 
Page 1 ofN 
Page 51 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Patient 
Body System I 
Cohort 
Number 
MedDRA Term I 
AETerm 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.7 Listing of Adverse Events by Cohort 
Treatment Start /End 
Relationship 
Action Taken/ 
Area 
Date 
Severity to Study 
Outcome Other Action 
SAE? 
Drug 
Taken 
Cohort 1 
xx-xxxx 
Nervous system disorders I No 
yyyy-mm-dd I Mild 
Not Related 
Recovered Dose Not Changed/ No 
Cohort 2 
Cohort 3 
Cohort 4 
Headache I 
Headache 
Related= Possible, Probable, Definite 
Created on: ddmmmyy hh:mm 
05/19/2017 
yyyy-mm-dd 
None 
Page 1 ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 52 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.8.1 Listing of Positive Pregnancy Test Results 
Cohort 
Cohort I 
Cohort 2 
Cohort 3 
Cohort 4 
Created on: ddmmmyy hh:mm 
05/1912017 
Patient 
Number 
xx-xxxx 
Visit 1 
Negative 
Visit 2 
Negative 
• Taro Pharmaceuticals U.S.A., Inc. • 
Visit 3 
Negative 
Page I ofN 
Page 53 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Cohort 
Patient 
Number 
Cohort I 
xx-xxxx 
Cohort 2 
Cohort 3 
Cohort 4 
Created on: ddmmmyy hh:mm 
05/1912017 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.8.2 Listing of Abnormal Vital Signs 
Age 
Visit 
Vital Sign 
Normal Range 
Result 
XXX 
Diastolic BP 
XXX- XXX 
XXX 
2 
3 
Page I ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 54 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.8.3 Listing of Abnormal Physical Examination Results 
Cohort 
Cohort I 
Cohort 2 
Cohort 3 
Cohort4 
Created on: ddmmmyy hh:mm 
0511912017 
Patient 
Number 
xx-xxxx 
Visit 
2 
3 
System 
HEENT 
• Taro Pharmaceuticals U.S.A., Inc. • 
Results 
Abnormal (Scar) 
Page 1 ofN 
Page 55 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.8.4 Listing of Clinical Hematology Laboratory Results 
Cohort 
Cohort I 
Cohort 2 
Cohort 3 
Cohort4 
Patient 
Number 
xx-xxxx 
Created on: ddmmmyy hh:mm 
05/19/2017 
Visit 
I 
3 
Hematocrit 
WBC 
Platelets 
Hemoglobin 
(unit) 
(unit) 
(unit) 
(unit) 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
• Taro Pharmaceuticals U.S.A., Inc. • 
XXX 
XXX (Low) 
etc. 
XXX 
XXX 
Page I ofN 
Page 56 of64 


Taro Pharmaceuticals U.S.A., Inc. 
Desoximetasone 0.15% Topical Spray 
Novum Pharmaceutical Research Services 
Protocol I Study No. DSXS 1502a I 71615002 
L16.2.8.5 Listing of Clinical Chemistry Laboratory Results 
Cohort 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Patient 
Number 
xx-xxxx 
Created on: ddmmmyy hh:mm 
0511912017 
Visit 
1 
3 
Alkaline 
Alnine 
Aspartate 
Blood Urea 
Phosphatase 
Transaminase Transaminase 
Nitrogen 
etc. 
(unit} 
(unit} 
(unit} 
(unit} 
XXX 
XXX 
XXX (High) 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX 
Page 1 ofN 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 57 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
10. APPENDICES 
APPENDIX A: Body Surface Area Calculation 
Total Body Surface Area Calculation 
To calculate the Total BSA the following procedure (Mosteller Formula13) should be followed. 
Total Body Surface Area (BSA) in meters squared 
m2 =((height (em) x weight (kg)) 13600)
12 
It is preferable that the patient's height and weight be 
measured in em and kg however if needed: 
To convert inches (in) to centimeters (em) the following 
conversion should be used 
1 inch = 2.54 em 
To convert pounds (lbs) to kilograms (kg) the following 
conversion should be used 
lib= 0.45 kg 
The patient's height and weight should be reported to the nearest em and nearest 0.5 kg. The 
BSA should be reported to the nearest second decimal place. 
For example a patient who is 68 inches tall and weighs 180 lbs will have a reported BSA of: 
68 in x 2.54 = 173 em 
180 lb X 0.45 = 81.0 kg 
BSA 
= SQRT ((173 x 81.0)13600) 
= 1.97 m2 
%BSA Affected 
To estimate the % BSA Affected, the Investigator should use the method of approximation: 
The "Rule ofNines" provides a general estimation oftotal BSA for several anatomic 
areas (each arm = 9%, each leg = 18%, back = 18%, chest and abdomen = 18%, head = 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 58 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
9%, groin= 1%). The Investigator may then visually estimate the proportion ofthe 
involved skin within each anatomic area and calculate the total percentage ofBSA 
affected. In children, hips and legs are smaller and the head, neck and shoulders are 
larger, as a result, a modified "Rule of Nines" is used (see diagram below). 
1-4 year child 
5-9 year child 
10-14 year child 
Adult body 
Part 
body 
body 
body 
% oftotal 
% oftotal 
% oftotal 
% oftotal 
............. ~ "'""''"'""'''''"''"'ri"''"'''"' 
Arm 
9.5% 
9.5% 
9.5% 
9% 
Head 
12% 
9% 
.............................................. 
19% 
15% 
Neck 
1% 
1% 
............... ................ 
Leg 
15% 
17% 
18% 
18% 
Anterior trunk 
16% 
16% 
16% 
18% 
Posterior trunk 
16% 
16% 
16% 
18% 
9% 
1-4 
5-9 
10-14 
ADULT 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 59 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
APPENDIX B: Eczema Area and Severity Index Score (EASI) 
The EASI is a composite score based on the severity of four different signs of atopic dermatitis in 
four different areas ofthe body multiplied by the percent of that specific body area affected 
multiplied by a weighting factor. 
Erythema 
0 =Clear 
1 =Mild 
2 =Moderate 
3 =Severe 
No evidence of erythema 
Definite light red coloration 
Moderate redness, but not dark 
Dark red coloration 
Induration/papulation/edema 
0 = Clear 
No evidence of any induration/papulation/edema 
1 = Mild 
Barely perceptible elevation 
2 = Moderate 
Clearly perceptible elevation 
3 = Severe 
Marked and extensive elevation 
Lichenification 
0 =Clear 
1 =Mild 
2 =Moderate 
3 =Severe 
Excoriation 
0 =Clear 
1 =Mild 
2 =Moderate 
3 =Severe 
No evidence of lichenification 
Slight thickening of skin discerible only by touch and with 
skin markings minimally exaggerated 
Definite thickening of skin with skin marking exaggerated so 
at they form a visible criss-cross or ridged pattern 
Thickened skin with skin markings visibly portraying an 
exaggerated criss-cross or ridged pattern 
No evidence of excoriation 
Scant evidence of excoriation with no signs of deepers skin 
damage (absence of erosion or crusts) 
Several linear marks of skin with some showing evidence of 
deeper skin injury (erosion, crust visible) 
Many erosive or crusty lesions present 
The patient will be required to rate the severity of their pruritis (itching/scratching/discomfort) over 
the previous 24 hours using the following scale: 
Pruritis 
0 =None 
1 =Mild 
2 =Moderate 
05119/2017 
None 
Occasional slight itching or scratching 
Constant or intermittent itching/scratching/discomfort which 
is not disturbing sleep 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 60 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
3 =Severe 
Bothersome itching/scratching/discomfort which is 
disturbing sleep 
Eczema, induration, excoriation and lichenification are part of the EASI score but pruritis is not. 
EASI Score 
The EASI score is calculated as follows: 
Head/neck 
(E + I + X + L) x Area x 0.1 (in children ages 0-7, x 0.2) 
Upper Limbs (E +I+ X+ L) x Area x 0.2 
Trunk 
(E +I+ X+ L) x Area x 0.3 
Lower Limbs (E +I+ X+ L) x Area x 0.4 (in children ages 0-7, x 0.3) 
EASI SCORE= SUM OF ABOVE 4 REGIONS 
E: 
Erythema, 
I: 
Induration/papulation/edema 
X: 
Excoriation 
L: 
Lichenification 
Severity is based on the Investigator's assessment of individual signs and symptoms 
0 = none, 1 = mild, 2 = moderate, 3 = severe using the definitions above 
The %of each body region affected is scored as the variable Area above in the 
EASI formula. For the 4 body regions (head/neck, upper limbs, trunk and lower 
limbs) ifthe: 
Area= 0 
Area= 1 
Area= 2 
Area= 3 
Area= 4 
Area= 5 
Area= 6 
if% affected is 0% 
if% affected is 1 to 9% 
if% affected is 10 to 29% 
if% affected is 30 to 49% 
if% affected is 50 to 69% 
if% affected is 70 to 89% 
if% affected is 90 to 1 00% 
EASI Score can be presented to the nearest whole number (no decimals and all numbers should be 
rounded, 0.5 should be rounded up to the nearest whole number) 
The minimum score would be 0 and the Maximum Score would be 72. To be eligible for 
participation in this study a patient must have an EASI of at least 15 at baseline. 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 61 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
APPENDIX C: Investigator Global Assessment (IGA) 
To be eligible for inclusion in the study the IGA must be 3 or 4 at baseline. To be considered a 
Clinical Success the patient must score a 0, 1 at Visit 4. 
0 
Clear 
Minor, residual discoloration, no erythema or 
induration/papulation, no oozing/crusting 
1 
Almost Clear 
Just perceptible erythema, with almost no induration/papulation 
and no oozing/crusting 
2 
Mild Disease 
Definite pink erythema with mild induration/papulation and no 
oozing/ crusting 
3 
Moderate 
Disease 
4 
Severe 
Disease 
05119/2017 
Red erythema with moderate induration/papulation and there 
may be some oozing/crusting 
Dark/bright red erythema with severe induration/papulation 
with oozing/crusting 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 62 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
APPENDIX D: Cortisol Response Test 
This cortisol release test is modified from the procedure of Wood et a! as described in the 
Product Label for Cortrosyn™ (cosyntropin) for injection (Amphstar Pharmaceuticals, Inc.). 
The procedure is as follows: 
1. A single 5 ml blood sample should be taken as the basal sample. 
2. 0.25 mg (a single vial) of Cortrosyn ™ (cosyntropin) should be reconstituted with l.Oml 
of0.9% sodium chloride injection USP injected intramuscularly. In patients under 3 years 
of age, 0.125mg of Cortrosyn ™ will be used. 
3. 30 minutes after the IM injection a second 5 ml blood sample should be obtained. The 
resulting two serum samples (at least 1 ml of serum in each) should be processed and 
labeled according to the instructions provided and sent the same day to ACM Global 
Laboratory for analysis of basal and post stimulated serum cortisol concentration. 
At Visit 1 and Visit 4 all patients will have a cortisol response test performed. The resulting 
blood sample should be sent to ACM Global Laboratory for immediate testing. 
Visit 1 Test 
The results of the cortisol response test must be obtained prior to study drug being dispensed at 
Visit 2. Only patients with normal baseline (Visit I) cortisol and adrenal function (see 
criteria 
below) should be enrolled in the study. 
Visit 4 Test 
The test at the End of Study visit should not be performed if the patient dosed within 12 hours. 
A patient will be considered to have normal basal cortisol level and adrenal function if they meet 
all three criteria listed below under Normal. Failure to meet any of these criteria is indicative of 
abnormal adrenal function or potential HP A axis suppression. 
Cortisol Results 
Normal 
Abnormal 
Basal 
(pre Cortrosyn ™ 
:::=: 5 mcgl1 OOml 
< 5 mcgl1 OOml 
injection) 
30 minutes post 
> basal value + 7 
< basal value + 7 
Cortrosyn™ 
> 18 mcg/1 OOml 
:S 18 mcgll OOml 
injection 
HP A Axis suppression will be defined as a 30 minute post Cortrosyn TM injection level cortisol 
level of :S 18 mcgll OOml. As the study treatment period will be over, any patients with results of 
0511912017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 63 of64 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
Desoximetasone 0.15% Topical Spray 
Protocol I Study No. DSXS 1502a I 71615002 
HPA axis suppression will be advised not to initiate any new steroid therapy, topical or 
otherwise, and to return to the site in 28 days at which time they will be assessed for HPA axis 
suppression. 
Any patient presenting with symptoms of HP A axis suppression, such as nausea, headache, 
myalgia, fatigue or loose stool, will be referred to an endocrinologist. As an additional safety 
precaution, wristbands identifying the patient as someone suffering from adrenal suppression 
secondary to steroid 
withdrawal will be provided to alert medical personnel should any 
emergencies arise before adrenal function returns to normal. 
If the results of the cortisol response test still show signs of HPA axis suppression 28 days after 
discontinuing therapy the patient will be asked to return in 28 days (56 days after discontinuing 
steroid therapy) for another follow-up test. If the patient is still showing signs of HPA axis 
suppression 56 days after discontinuing steroid therapy and presents with related symptoms, the 
patient will be referred to an endocrinologist. 
If HPA axis suppression persists for 56 days after discontinuing steroid therapy, but the patient 
has no symptoms they will be asked to return in 28 days (84 days after discontinuing steroid 
therapy) for another follow-up test. If HPA axis suppression persists for 84 days after 
discontinuing steroid therapy patients will be referred to an endocrinologist regardless of 
symptoms. 
Patients should not be subjected to Cortrosyn TM testing, or any other challenge to their adrenal 
response, any sooner than 4 weeks from their last CortrosynTM test. 
Follow-Up Schedule for Patients showing signs ofHPA Axis Suppression 
Days 
HPA Results 
Symptoms 
Patient Course 
after d/c 
28 
Normal 
N/A 
Study over 
28 
Abnormal 
Yes 
Refer to endocrinologist 
28 
Abnormal 
No 
Repeat test in 28 days 
56 
Normal 
N/A 
Study over 
56 
Abnormal 
Yes 
Refer to endocrinologist 
56 
Abnormal 
No 
Repeat test in 28 days 
84 
Normal 
N/A 
Study over 
84 
Abnormal 
Yes or No 
Refer to an endocrinologist 
05/19/2017 
• Taro Pharmaceuticals U.S.A., Inc. • 
Page 64 of64