Clinical trial NCT02321540
Conditions: Lung Cancer
Keywords: Lung Cancer Non-small cell lung cancer NSCLC Epidermal growth factor receptor mutations EGFR Recurrent non-small cell lung cancer Ibrutinib PCI-32765 Imbruvica
Sponsor: M.D. Anderson Cancer Center
Start date: 2015-03-31; Completion date: 2021-09-16
Enrollment: 13 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of Part 1 of this clinical research study is to find the highest dose of (Imbruvica) ibrutinib that can be given to patients with non-small cell lung cancer (NSCLC). The goal of Part 2 of this clinical research study is to learn if the dose of ibrutinib found in Part 1 can help to control the disease.

The safety of this drug will also be studied in both parts of the study.

Detailed description:
Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of up to 6 participants will be enrolled in Part 1 of the study, and up to19 participants will be enrolled in Part 2.

If you are enrolled in Part 1, the dose of ibrutinib you receive will depend on when you join this study. The first group of participants will receive the lowest dose level of ibrutinib. Each new group will receive a higher dose of ibrutinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ibrutinib is found.

If you are enrolled in Part 2, you will receive ibrutinib at the highest dose that was tolerated in Part 1.

Study Drug Administration:

You will take ibrutinib pills 1 time each day, at about the same time every day. You may take your dose of ibrutinib with or without food.

Study Visits:

Each cycle is 4 weeks.

On Day 1 of all cycles:

* You will have a physical exam
* Blood (about 3 teaspoons) will be drawn for routine tests.
* On Cycle 2 only, blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing before your dose and then 4 more times over the next 6 hours after your dose. PK testing measure the amount of study drug in the body at different timepoints.
* If you the doctor thinks it is needed, blood (about ½ teaspoon) or urine will be collected for pregnancy testing.

Every 8 weeks, you will have a CT, MRI, or x-ray to check the status of the disease. You will have the same type of scan performed as you did at screening.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

End-of-Dosing Visit:

About 30 days after your last dose of study drug:

* You will have a physical exam.
* Blood (about 3 teaspoons) will be drawn for routine tests.
* If you the doctor thinks it is needed, blood (about ½ teaspoon) or urine will be collected for pregnancy testing.

Follow Up Visits:

Every 6 months you will be asked to come into the clinic or you will be called by a member of the study staff to ask how you are doing and if you have started any new anti-cancer treatments. If you are called, it should take about 10 minutes.

This is an investigational study. Ibrutinib is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). It is considered investigational to use this drug to treat NSCLC. The study doctor can explain how the study drug is designed to work.

Up to 43 participants will be enrolled on this study. All will take part at MD Anderson.

Arms: arm 1: Participants in Part 1 receive dose level of Ibrutinib depending on study joined. First group of participants receive lowest dose level of Ibrutinib. Each new group receives a higher dose of Ibrutinib than the group before it, if no intolerable side effects were seen. This continues until highest tolerable dose of Ibrutinib is found.

Participants in Part 2 receive Ibrutinib at highest dose that was tolerated in Part 1 or 840 mg daily.

Starting level of Ibrutinib: 560 mg by mouth daily in a 28 day cycle.
Interventions: intervention 1: Ibrutinib
Intervention descriptions: intervention 1: Part 1 Starting level of Ibrutinib: 560 mg by mouth daily in a 28 day cycle.

Part 2 Starting level of Ibrutinib: Maximum tolerated dose from Part 1 or 840 mg daily.

Protocol documents:
Prot_SAP_000.pdf: 
	

	 	!"#	$
%&$	'
())*+,-./,-0(2-/2*   4
5	
 6
$	'$
7*,-8,9.:-;2</,0./)*
=	>? 6
@A@AB'#C?4DEFG
B
?HIIDFD
JKI@F"ILG"MFMF
	5KI@F"ILG"@GGD
N	&O#	
>&
()P-;2</,0./)*<
&#? 6
@A@AB'#C?4DEFG
B
?HIIDFD
JKI@F"ILG"MFMF
	5KI@F"ILG"@GGD
&
#O#	
>&
QR>B#	'? 6?6
@A@AB'#C?4DEFG
B
?HIIDFD
JKI@F"ILG"MFMF
	5KI@F"ILG"@GGD
S#	'O#	
>&


@
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()+,-+.%).%/
01
3456789:6;
1111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111=
010
>?@AB?C3DEFGH@IFJ111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111=
01K
;FGLMNB?C3DEFGH@IFJ11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111=
K1
4O7PQR3STU
11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111=
K10
6QVRWXHBMHTLMY;ABZZ7FZZ[XM\7BMGF?
11111111111111111111111111111111111111111111111111111111111=
K1K
9D?XH@M@D11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111]
K1^
RBH@LMBZF
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111_
K1=
7L??FZBH@IF;HXN@FJ4BG`\?LXMN
111111111111111111111111111111111111111111111111111111111111111111111111111111a
^1
>O896T8;6[67893T
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111a
^10
6Z@\@D@Z@HC7?@HF?@B
1111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111a
^1K
6bGZXJ@LM7?@HF?@B
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111110c
=1
8R6O8W6T8>[OT
1111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111100
=10
;HXNC;GdFAB11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111100
=1K
ULJF6JGBZBH@LMBMNO\FMHONA@M@JH?BH@LM
111111111111111111111111111111111111111111111111111111111110K
=1^
UFe@M@H@LMLeULJFY[@A@H@M\8Lb@G@HCfU[8g
111111111111111111111111111111111111111111111111111111110^
=1=
QFMF?BZ7LMGLA@HBMHWFN@GBH@LMJh>?LGFNX?FJhBMN;XiiL?H@IF7B?F
QX@NFZ@MFJ
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111110=
=1]
UX?BH@LMLe8dF?BiC
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111110j
=1k
UX?BH@LMLeVLZZLlSi
11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111110j
=1j
7?@HF?@BeL?RFALIBZe?LA;HXNC
1111111111111111111111111111111111111111111111111111111111111111111111111110j
]1
U3;9TQU6[Om;nU3;6W3U9V97O893T;1111111111111111111111111111111111111111111111111111111111111110j
k1
OU:6R;66:6T8;OTUR6>3R89TQ
1111111111111111111111111111111111111111111111111111111111111111111111110_
j1
94RS89T943:6RO[[;OV68m;SWWORm
11111111111111111111111111111111111111111111111111111111111111K=
j10
WLMLHdF?BiC;HXN@FJ
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111K=
j1K
8?FBHAFMHU@JGLMH@MXBH@LMJ
11111111111111111111111111111111111111111111111111111111111111111111111111111111111K]
_1
73RR6[O89:6h493WORP6RhOTU>oORWO73P9T6897;8SU96;
111111111111111111Kk
_10
4@LAB?`F?;HXN@FJ
11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111Kk
_1K
>dB?ABGL`@MFH@G;HXN@FJ
1111111111111111111111111111111111111111111111111111111111111111111111111111111111111111K_
a1
;8SUm>R376USR6;BMN7O[6TUOR
1111111111111111111111111111111111111111111111111111111111111111111111^c
a10
9MeL?AFN7LMJFMH111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111^c
a1K
WFN@GBZo@JHL?CBMN>dCJ@GBZ6bBA
1111111111111111111111111111111111111111111111111111111111111111111111^c
a1^
7Z@M@GBZ[BDL?BHL?C8FJHJ
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111^c
a1=
8XAL?4@LiJC
11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111^c
a1]
RBN@L\?Bid@GOJJFJJAFMH11111111111111111111111111111111111111111111111111111111111111111111111111111111111111^0
a1k
;HXNC7BZFMNB?1111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111^0
K
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'
)*+,-.*)*/023*33*40''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''56
%&'% +7898:;<=*>>?@8A,<B9C0:;<=D
''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''56
%%'
E+0+.*F2.0G/HI.*H-J+02.K.*L-G.*)*/0,
'''''''''''''''''''''''''''''''''''''''''''5M
%6'
,0+0G,0G4+J42/,GE*.+0G2/,'''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''5M
%6'% ,8:CNE?D9O7I*7CP<978D'''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''5M
%6'6 ,Q;PB?,9R?I+@@=:QB.Q8?
''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''5S
%6'5 +7QBND9D<>*7CP<978D
''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''5S
+FF*/EGT+
F*.32.)+/4*,0+0-,4.G0*.G+''''''''''''''''''''''''''''''''''''''''''''''''''U%
.*3*.*/4*,''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''U6

5
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&()*+,-./+0
%&%
3456748(9:;<=5>;?
@ABCDEFGDHIJKBLMENBOGDBMIPBMBDFEQBMABFGREFSFMITBDGMBPPIOBUFGREFSFCTGQQBPPIOBIV
EJDSMEQEJEQCGMEBQMOWEMAQIQXOFGTTLBTTTSQYLGQLBDGQPMIGOOBOOMABDBOCIQOBDGMBWEMAEJDSMEQEJ
EQCGMEBQMOWEMAQIQXOFGTTLBTTTSQYLGQLBDAGDJIDEQYZ[\]FSMGMEIQOWEMACDIYDBOOEIQIQ
Z[\]@^_O`
%&a
0;<bcd748(9:;<=5>;?
eBLIQPGDHIJKBLMENBOGDBMIGOOBOOf
g ]BOCIQOBDGMBEQCGMEBQMOWEMAiZ]jFSMGQMQIQXOFGTTLBTTTSQYLGQLBD
g kEOBGOBLIQMDITDGMBlPBVEQBPGODGMBIVOMGJTBPEOBGOBmCGDMEGTDBOCIQOBmLIFCTBMB
DBOCIQOBn
g oNBDGTTOSDNENGT
g pDIYDBOOEIQXVDBBOSDNENGT
g eGVBMHGQPMIRELEMHCDIVETB
g kSDGMEIQIVDBOCIQOB`
ZRCTIDGMIDHIJKBLMENBOGDBf
g @IGOOBOOFITBLSTGDFGDqBDOGOOILEGMBPWEMADBOEOMGQLBGQPDBOCIQOBrEQLTSPEQY
OBLIQPGDHFSMGMEIQO`
g @ICBDVIDFCAGDFGLIqEQBMELOMSPEBO
a&)s,tuv(wxy
a&%
+uzv{|=7c=7cd}+va{|=7c=xbc~067,;|c,7c<;4
LMENGMEQYFSMGMEIQOEQMABBCEPBDFGTYDIWMAVGLMIDDBLBCMIDlZ[\]nGDBVISQPEQGCCDIREFGMBTH
MIIVCGMEBQMOWEMAQIQXOFGTTLBTTTSQYLGQLBDlen`
rj\IDMABOBCGMEBQMOrMDBGMFBQM
WEMAZ[\]MHDIOEQBqEQGOBEQAEJEMIDOBDTIMEQEJrGVGMEQEJrIDYBVEMEQEJl@^_OnEOGOOILEGMBPWEMA
AEYADBOCIQOBDGMBOGQPEFCDINBPCDIYDBOOEIQVDBBGQPINBDGTTOSDNENGT`
rQVIDMSQGMBTHr
GLSEDBPDBOEOMGQLBEQBNEMGJTHPBNBTICOrILLSDDEQYGMGFBPEGQIVMIFIQMAOGVMBDMDBGMFBQM
EQEMEGMEIQ`NGDEBMHIVDBOEOMGQLBFBLAGQEOFOAGNBJBBQEPBQMEVEBPrEQLTSPEQYMABOBLIQPGDH
Z[\]FSMGMEIQr@`
XMMBFCMOMIMGDYBMMAEODBOEOMGQMCICSTGMEIQAGNBJBBQDBTGMENBTH
SQOSLLBOOVSTMIPGMBrWEMAMABEDDBNBDOEJTBZ[\]EQAEJEMIDGVGMEQEJOAIWEQYQIOSDNENGTJBQBVEM
LIFCGDBPMICTGLBJIEQCGMEBQMOWAIAGNBVGETBPMABDGCHWEMABDTIMEQEJIDYBVEMEQEJ`

oMABDFGKIDTEFEMGMEIQOIVMABGCCDINBPZ[\]@^_OLSDDBQMTHGDBMABEDMIRELEMEBOrCGDMELSTGDTH[_
GQPOqEQBVVBLMOrWAELAGDBPSBMIEQAEJEMEIQIVWETPXMHCBZ[\]`
X@ABDBEOMABDBVIDBGQSDYBQM
SQFBMQBBPVIDQBWGYBQMOMAGMEQAEJEMMABFSMGMBPZ[\]MHDIOEQBqEQGOBrEQLTSPEQYMAIOBWEMA
DBOEOMGQLBFSMGMEIQOOSLAGO@rWAETBFEQEFEEQYMIRELEMEBODBTGMBPMIEQAEJEMEIQIVMAB
WETPXMHCBZ[\]DBLBCMID`
iZ]jFSMGMEIQOAGNBJBBQPBOLDEJBPEQGJISMjIVCGMEBQMOWEMAe`@ABDBGDBQI
GCCDINBPMGDYBMBPMABDGCEBOVIDCGMEBQMOWEMAMABOBFSMGMEIQO`

Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&%
()*+,-.-)
123456762689:6385;67;<=988>?@5A75>@39==B9CD67685A3AC<@E9=A75=B;267C67F67G6265@3@:H345@7I8
5B3@867AJ6798AKHLMNO17G62656@7@:HLM2=@<J8C@P7853A9DH;<A==3A<A?5@3KHQRN86F79=67F
?95GP9B897C5G48?3AEA758H;<A==?3@=6:A3956@7O17E653@>62345676267G62658?436:6ACHLM97C
8A=A<5ACDAD2A38@:5GAJ6798A:9D6=BP65GST;:@=C8?A<6:6<65B<@D?93ACP65G7@7;HLMJ6798A8O
123456762K1UHRVW1QXYN689??3@EAC2B5GAVOZO[@@C97C\34FXCD676853956@7K[\XN:@3
5GA53A95DA75@:]SND975=A<A===BD?G@D9KUQ^N67?956A758PG@G9EA3A<A6EAC95=A985@7A
?36@35GA39?B298AC@7@EA39==3A8?@78A395A>_N<G3@76<=BD?G@<B56<=A4JAD69KQ^^N67?956A758
PG@G9EA3A<A6EAC95=A985@7A?36@35GA39?B>`NQ^^67?956A758P65GSa?CA=A56@797CbN
c9=CA7853dDI8U9<3@F=@24=67AD69O12345676268<433A75=B47CA367EA856F956@767E936@48
67C6<956@78O
H<A==893A=BD?G@<B5A8P65GD4=56?=A:47<56@78675GA6DD47A3A8?@78A>67<=4C67F9756FA7
?3A8A75956@7>97562@CB?3@C4<56@7>97C<B5@J67A3A=A98AOH;<A==8Ae?3A88<A==843:9<A
6DD47@F=@24=678<@D?36867F5GAH;<A==3A<A?5@3KHQRN>PG6<G689<56E95AC2B267C67F5@
9756FA7OX756FA7267C67F67C4<A83A<A?5@39FF3AF956@797C5GA<=485A367F97C9<56E956@7@:
D4=56?=A5B3@867AJ6798A8>PG6<G6754379<56E95A:435GA3C@P7853A9D86F79=67F?95GP9B8O
S_
LGA?3@<A88@:H;<A==D9543956@7>67<=4C67F6DD47@F=@24=67<G9673A93397FADA7597C8@D956<
D45956@7>6856FG5=B3AF4=95ACO15685G@4FG55G95H;<A===BD?G@D9897CQ^^3A84=5:3@D
D45956@7897C53978=@<956@789<f463ACC4367F7@3D9=H;<A==CAEA=@?DA75O
S`ZAEA39==67A8@:
AE6CA7<A84FFA855G9586F79=67F5G3@4FG5GAHQR687A<A8893B5@84859675GAE6926=65B@:H;<A==
D9=6F797<6A8O
LGA3@=A@:HLM67HQR86F79=53978C4<56@768CAD@785395AC2B5GAG4D97FA7A56<
6DD47@CA:6<6A7<BC68A98Ag;=67JAC9F9DD9F=@24=67AD6997C5GAD@48AFA7A56<C68A98Ag;
=67JAC6DD47@CA:6<6A7<B>2@5G<948AC2B9D45956@7675GAHLMFA7AOLGA8AFA7A56<C68A98A8
93A<G939<5A36hAC2B3AC4<ACHQR86F79=67F97C9:96=43A5@FA7A395AD9543AH;<A==8OLGAHLM
?3@5A6768Ae?3A88AC67D@85GAD95@?@6A56<<A==8P65G5GAAe<A?56@7@:L;<A==897C795439=J6==A3
<A==8>2455GA8A=A<56EAA::A<5@:HLMD45956@7884FFA8585G95658?36D93B:47<56@79=3@=A6867
9756FA73A<A?5@386F79=67F67H;<A==8O
Sb
\959:3@DZ54CBiQjQ;Tbak`CAD@785395A5G959=5G@4FG6234567626839?6C=BA=6D6795AC:3@D5GA
?=98D99:5A3@39=9CD676853956@7>@7<AC96=BC@867FP65G623456762689CAf495A5@8485967D9e6D9=
lmnopnqrstunpvqnqxvyvxtzro{|mr}o~lr~xsr~nxsr~y~{pux}st;
Tbak`>5GAHLM@<<4?97<6A8:@35GA_OkDFJFC9B5@S_OkDFJFC9B<@G@35897C:@35GA
kTDF<@75674@48C@867F<@G@35>PA3A9==92@EAT95A65GA3b@3_bG@4389:5A3C34F
9CD676853956@7O
[@35GAD@85<@D?3AGA786EA7@7<=676<9=97C<=676<9=67:@3D956@73AF93C67F62345676229<JF3@47C>
89:A5B>A::6<9<B>97C67E653@97C67E6E@?3A<=676<9=9<56E65B97C5@e6<@=@FB@:623456762>3A:A35@
5GA=95A85EA386@7@:5GA62345676217EA856F95@3
8H3@<G43AO
k
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&%&' )*++,-.01203456364,57,8,
90-8:;+0<840+=-;:;3<6>;303456364,5,3?456364,56310-+,8603-;@,-?63@6A-*8636AB
=5;,<;-;1;-808:;4*--;38>;-<603018:;C3>;<86@,80-D
<E-04:*-;&
%&%&% F:,-+,4050@.
CA-*8636AG,<?;<6@3;?,<,<;5;486>;,3?40>,5;3863:6A680-018:;E8H&
'IC3>68-0B
6A-*8636A6<,=08;3863:6A680-01E8H,486>68.JCKILML&NO3PQ&R:;6--;>;-<6A5;A63?63@
016A-*8636A804.<8;63;STU'638:;,486>;<68;01E8H-;<*58<63<*<8,63;?63:6A6860301E8H
4,8,5.864,486>68.,3?;3:,34;?<;5;486>68.0>;-08:;-H63,<;<8:,8?03084038,63,
4.<8;63;,88:6<=0<68603&V:;3,??;??6-;485.80:*+,3G:05;A500?B6A-*8636A63:6A68<
<6@3,58-,3<?*486031-0+8:;ES4;55-;4;=80-,3?A504H<=-6+,-.ES4;55,486>,8603JCKILM
UL3PQ,<,<<,.;?A.,386SC@P<86+*5,860310550G;?A.K7WO;X=-;<<603&
'W
90-+0-;?;8,65;?,3?40+=-;:;3<6>;6310-+,8603-;@,-?63@303456364,5=:,-+,4050@.
,3?80X64050@.B=5;,<;-;1;-808:;4*--;38C3>;<86@,80-Y<E-04:*-;&
%&%&N R0X64050@.
C3<,1;8.=:,-+,4050@.,<<;<<+;38<B308-;,8+;38S-;5,8;?;11;48<G;-;0A<;->;?638:;
4;38-,53;->0*<<.<8;+0--;<=6-,80-.<.<8;+63-,8<,8,3.?0<;8;<8;?&9*-8:;-B30
8-;,8+;38S-;5,8;?40--;48;?ZR638;->,5JZR4Q=-0503@,8603;11;48G,<0A<;->;?,8,3.
8;<8;??0<;63,4,-?60>,<4*5,-<8*?.*<63@8;5;+;8-.S+03680-;??0@<&
E,<;?03?,8,1-0+-,8,3??0@6345*?63@@;3;-,580X6468.<8*?6;<*=80'NG;;H<
?*-,8603B8:;@-;,8;<8=08;386,510-:*+,380X6468.G68:6A-*8636A6<=-;?648;?80A;63
5.+=:06?86<<*;<J5.+=:06??;=5;8603Q,3?8:;@,<8-0638;<863,58-,48J<0181;4;<[?6,--:;,
G68:0-G68:0*86315,++,8603Q&\??68603,580X6468.163?63@<<;;363035.03;<=;46;<G68:
300A<;->;?:*+,340--;5,8;63456364,5<8*?6;<80?,8;6345*?;=,34-;,864,463,-4;55
,8-0=:.J-,8QB+636+,55.?;4-;,<;?8-,A;4*5,-,3?40-864,5A03;J-,8Q,3?40-3;,5
?.<8-0=:.J?0@Q&
C3>68-0,3?63>6>0@;3;86480X6468.<8*?6;<<:0G;?8:,86A-*8636A6<308@;3080X64&C3,
-,8;+A-.0S1;8,580X6468.<8*?.6A-*8636A,?+636<8-,8603G,<,<<046,8;?G68:1;8,550<<,3?
+,510-+,8603<J8;-,80@;36468.Q,86A-*8636A?0<;<8:,8-;<*5863,==-0X6+,8;5.W86+;<,3?
'T86+;<8:;;X=0<*-;J\]KQ63=,86;38<,?+636<8;-;?8:;?0<;01IWL+@?,65.B
-;<=;486>;5.&
%&%&N&'
K,-4630@;3;<6<BP*8,@;3;<6<BC+=,6-+;38019;-86568.
K,-4630@;36468.<8*?6;<:,>;308A;;3403?*48;?G68:6A-*8636A&
W
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()*+*&-./+0)1().23+*4*+.&.4)3'*.51().23+*4*)67813/9.//.6:-./+0)
45./)023+*4*+.4;'010/013.&3''.)*0+.//.6*+1.11.5*.+7<=>94355/:+0'-./*)
45./)023+*4*+.+*+?*?0&0+31.''0-1*4'0+(453(/.//.6*+1*43.)@0/3/(A)0
BCCC12DE2F
G3')*5*)6/)(@*3/-*);*&'()*+*&;.?3+0)&33+40+@(4)3@*+.+*1.5/F%+);323+3'.5
)0H*405026/)(@*3/40+@(4)3@*+'.)/.+@@02/:0'.556.@1*+*/)3'3@*&'()*+*&@*@+0)
'3/(5)*+.@?3'/33II34)/0+'3A'0@(4)*?30'2.+/F
BFBFJ L(11.'60I<5*+*4.5M.).
G0');310/)401A'3;3+/*?345*+*4.5*+I0'1.)*0+'32.'@*+2*&'()*+*&:A53./3'3I3')0);3
4(''3+)?3'/*0+0I);3%+?3/)*2.)0'N
/O'04;('3F
%+.A;./3%%/)(@6*+A.)*3+)/-*);1.+)534355561A;01.:PPPA.)*3+)/'343*?3@0'.5
*&'()*+*&.).@0/30IQRC12@.*56F855A.)*3+)/;.@'343*?3@.)53./)0+3A'*0'
4;310);3'.A3()*4'32*13+:-*);.13@*.+0I);'33A'*0''32*13+/FS'3.)13+)-./-355
)053'.)3@T);310/)40110+.@?3'/33?3+)/-3'350-2'.@3@*.'';3.:+.(/3.:.+@
I.)*2(3FS;310/)40110+2'.@3UDJ.@?3'/33?3+)/-3'3+3()'0A3+*..+@
);'01&046)0A3+*.*+PRV.+@PPV0IA.)*3+)/:'3/A34)*?356FS;3'3/A0+/3'.)3)0
);3'.A6-./RWV:-*);BPV0IA.)*3+)/;.?*+2.401A53)3'3/A0+/3FS;313@*.+
A'02'3//*0+I'33/('?*?.50+);*//)(@6-./PUFX10+);/Y13@*.+0?3'.55/('?*?.5;./+0)
63)&33+'3.4;3@F
PZ
%+.A;./3%&D%%/)(@63+'055*+2A.)*3+)/-*);'35.A/3@0''3I'.4)0'64;'0+*4561A;046)*4
53(E31*.:WQA.)*3+)/'343*?3@0'.5*&'()*+*&.)@0/3/0IJBC120+43@.*560'WJC12
0+43@.*56F82.*+:)'3.)13+)-./-355)053'.)3@:.+@);310/)40110+.@?3'/33?3+)/
-3'3@*.'';3.:(AA3''3/A*'.)0'6)'.4)*+I34)*0+:.+@I.)*2(3F[0/)0I);3/3-3'350-
2'.@3FS;310/)40110+2'.@3UDJ.@?3'/33?3+)-./+3()'0A3+*.:-;*4;044(''3@*+
PQV0IA.)*3+)/F\00);3'2'.@3UDJ3?3+)044(''3@*+10'3);.+QV0IA.)*3+)/FS;3
0?3'.55'3/A0+/3'.)3-./ZPV.+@-./+0)/*2+*I*4.+)56@*II3'3+)&3)-33+);350-@0/3
.+@;*2;@0/32'0(A/F8)BR10+);/:3/)*1.)3@A'02'3//*0+I'33/('?*?.5-./ZQV.+@
0?3'.55/('?*?.5-./WUVF
PW
BFBFQ ];.'1.40E*+3)*4/.+@]'0@(4)[3).&05*/1
G0550-*+20'.5.@1*+*/)'.)*0+0I*&'()*+*&.)@0/3/'.+2*+2I'01PFBQ)0PBFQ12DE2D@.6
./-355./I*H3@@0/353?35/0IJBC:QRC:.+@WJC12D@.6:3HA0/('3)0*&'()*+*&*+4'3./3@
./@0/3/*+4'3./3@-*);/(&/).+)*.5*+)3'/(&^34)?.'*.&*5*)6FS;313.+;.5I5*I37)
PDB90I
*&'()*+*&.4'0//U45*+*4.5/)(@*3/'.+23@I'01J)0X;0('/:-*);.13@*.+)*13)0
1.H*1(1A5./1.40+43+)'.)*0+7S1.H90IB;0('/F8@1*+*/)'.)*0+0IJBC12*&'()*+*&
-*);.;*2;_I.)&'3.EI./)*+/(&^34)/-*);4;'0+*4561A;046)*453(E31*.7<``9
.AA'0H*1.)356@0(&53@);313.+/6/)31*43HA0/('3401A.'3@)0*+).E3.I)3'0?3'+*2;)
I./)*+2-*);13@*.+)*13)0S1.H@35.63@I'01B)0J;0('/F%&'()*+*&-./3H)3+/*?356
Z
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()*+,-&.'*'0&.,01.2*.,*+%&'()*+,'&34567899:;(2&<&2=,)+&,>0,),'*2*?@'A;B,'0
(CC2*D,%('&+1E8',%&=+*B&2,>0,),'*21C*'&>F1F*%C(2&.'*,)2G',>,)HI0&%&'()*+,'&6
'*6C(2&>'JK42(',*2(>L&.?2*%MH:'*NH7HO'&(.16='('&&DC*=G2&*?,)2G',>,)(>.3456
7899:B(=+&=='0(>96?*+.*??,2='.*=&&DC*=G2&H
I0&2&=G+'=*?0G%(>%(==)(+(>F&='G.1*?P
E74Q6,)2G',>,)F*>.GF'&.,>=,D0&(+'01%(+&
=G)R&F'=.&%*>='2('&.'0('+&=='0(>EMS*?'0&'*'(+.*=&*?P
E74Q6,)2G',>,),=2&>(++1
&DF2&'&.;B0&2&(=(CC2*D,%('&+1TMS,=2&F*<&2&.,>?&F&=HOG)R&F'=B,'0%,+.(>.
%*.&2('&2&>(+,>=G??,F,&>F1UF2&(',>,>&F+&(2(>F&VNM%WX%,>YB&2&&+,L,)+&'*&>2*++,>
O'G.134Z46EEM964J,>B0,F0C0(2%(F*A,>&',FU3[Y(==&==%&>'=B&2&,>F+G.&.H\*
.*=&(.RG='%&>',=>&&.&.?*2%,+.*2%*.&2('&2&>(+,%C(,2%&>'UL2&('&2'0(>NM
%WX%,>F2&(',>,>&F+&(2(>F&YHI0&2&,=>*.('(,>C(',&>'=B,'0=&<&2&2&>(+,%C(,2%&>'
*2C(',&>'=*>.,(+1=,=HI0&='G.1*?,)2G',>,),>0&C(',F,%C(,2&.=G)R&F'=,=FG22&>'+1,>
C2*L2&==H
]^_
abcdefbgh
5)2G',>,),=&??,F(F,*G=(>.B&++'*+&2('&.,>F&2'(,>+1%C0*%(=(>.+&GA&%,(=;)G','=(F',<,'1,>
=*+,.'G%*2=0(=>*'1&')&&>&D'&>=,<&+1='G.,&.HI*'&='B0&'0&2,)2G',>,)%,L0'0(<&G',+,'1,>
'0&'2&('%&>'*?+G>LF(>F&2;B&&<(+G('&.,'=(>','G%*2(F',<,',&=,>(C(>&+*?+G>LF(>F&2F&++
+,>&=)1G=,>L(F&++<,(),+,'1(==(1N.(1=(?'&2'2&('%&>'B,'0MHME'*NEGj,)2G',>,)Hk*2'0&
Nl\O4W4F&+++,>&='&='&.;'0&8MS,>0,),'*21F*>F&>'2(',*>U548MY*?,)2G',>,)2(>L&.?2*%
MHMM9'*NEmj;B,'0(>(<&2(L&*?E9H7mjHI02&&\O4W4F&+++,>&=B&2&0,L0+1=G=F&C',)+&'*
,)2G',>,);B,'0548M=)&'B&&>MHMM9(>.MHEl8mjHIB**?'0&=&F&+++,>&=0(2)*2(F',<(',>L
nokp%G'(',*>=q'0&'0,2.;'0*GL0nokpB,+.'1C&;&DC2&==&=F*>=','G',<&+1(F',<&nokp(>.,=
=&>=,',<&'*&2+*',>,)(=B&++H
r&>&D'F*%C(2&.&2+*',>,)(>.,)2G',>,)(>','G%*2(F',<,',&=,>>,>&\O4W4F&+++,>&=;=,D*?
B0,F00(<&%G'(',*>=*2.&+&',*>=,>'0&nokpL&>&Hk,<&*?=,Dnokp%G'(>'F&+++,>&=B&2&
=G=F&C',)+&'*)*'0&2+*',>,)(>.,)2G',>,);B,'0548M=sMH9mjHI0&tEl:8F&+++,>&;B0,F0
0(2)*2=(I:lMj%G'(',*>,>nokp;B(=2&=,='(>''*&2+*',>,))G'=G=F&C',)+&'*,)2G',>,)HI0&
&DC2&==,*>*?@I[B(=>*'.&'&F'()+&,>(++F&+++,>&='&='&.;,>.,F(',>L'0(',)2G',>,)6,>.GF&.
(>','G%*2(F',<,'1,>'0&=&F&++=,=>*'%&.,('&.)1@I[Hr&'0&>(>(+1-&.'0&&??&F'=*?
,)2G',>,)*>nokpC0*=C0*21+(',*>HI2&('%&>'*?tEl:8(>.tN988F&++=B,'0&2+*',>,)(>.
,)2G',>,)+&.'*(=,%,+(2.*=&6.&C&>.&>',>0,),',*>*?C0*=C0*26nokp(''0&ZEMuT=,'&,>
tN988F&++=Ht*B&<&2;*>+1,)2G',>,),>0,),'&.CZEMuT,>tEl:8F&++=B0,F00(2)*2'0&I:lMj
%G'(',*>HO,%,+(22&=G+'=B&2&*)=&2<&.,>*'0&2F&+++,>&=HI0*=&2&=G+'==GLL&='&.'0('
,)2G',>,)F(>?G>F',*>(=(>nokp,>0,),'*2,>\O4W4F&++=;&<&>'0*GL0,'.*&=>*'0(<&(76
(>,+,>*vG,>(-*+,>F*2&='2GF'G2&(=%*='*'0&2nokp,>0,),'*2=H
r&(+=*'&='&.,><,<*(F',<,'1*?,)2G',>,),>(D&>*L2(?''G%*2%*.&+.&2,<&.?2*%tEl:8F&++=H
I0&2&=G+'==0*B&.'0(''2&('%&>'B,'098%LXAL*?,)2G',>,)=,L>,?,F(>'+1=GCC2&==&.tEl:8
'G%*2L2*B'0(>.C2*+*>L&.=G2<,<(+*?'G%*2)&(2,>L(>,%(+=B0&>F*%C(2&.B,'0<&0,F+&
'2&('&.(>,%(+=H5>F*>'2(=';'2&('%&>'B,'08M%LXAL*?&2+*',>,)0(.>*&??&F'*>)*'0'G%*2
L2*B'0(>.=G2<,<(+,>'0&=(%&%*.&+;.&%*>='2(',>L,><,<*&??,F(F1*?,)2G',>,),>nokp
T
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()'()+,-./'0)01-,202'()'345657()7,-8
9,(.2/2(:,;0+,)7,/<01-&'0)01(7'0;0'=0)345657,...0),27(--=0)>()(7'0;('0/)?@AB
%&'('0/)8
C(2,+/)D-,E7.0)07(.+('(2&>>,2'0)>0)F010'0/)/<>-/:'F0)@GHA%&'()'345657,...0),2I
0)7.&+0)>'F/2,:0'F'F,JKLMN-,202'()7,%&'('0/)I:,D-/D/2,'F02DF(2,OO'-0(.'/+,',-%0),
'F,(7'0;0'=/<01-&'0)010)D('0,)'2:0'F34565F(-1/-0)>(7'0;('0)>@GHA%&'('0/)2:F/2,
'&%/-2F(;,D-/>-,22,+/)'F,-(D=:0'F,-./'0)01/->,<0'0)018C(2,+/)/&-D-,7.0)07(.+('(
2&>>,2'0)>(7'0;0'=0)?@AB%&'()'7,...0),2I:,:0..(.2/(22,22'F,(7'0;0'=/<01-&'0)010)
D('0,)'2:0'F?@AB%&'()'345658
PQR
TUVVWXYZ[\W^Z_`[WabYcdeVU_f`
g..D('0,)'2:0'F@GHA%&'('0/)2:0..1,-,h&0-,+'/F(;,'022&,(7h&0-,+(<',--,202'()7,'/()
@GHA'(->,',+'=-/20),i0)(2,0)F010'/-j,8>8,-./'0)01I>,<0'0)01I/-(<('0)01k89,:0..()(.=l,
'F02'022&,</--,202'()7,%,7F()02%2'/@GHA0)F010'/-2I2&7F(22,7/)+(-=%&'('0/)20)
JKLMNI(%D.0<07('0/)/<N@JI()+,D0'F,.0(.E'/E%,2,)7F=%(.'-()20'0/)j@NJk8
Km('0,)'2:0'F
?@AB%&'()'34565:0..1,-,h&0-,+'/F(;,'022&,(;(0.(10.0'=</../:0)>D-/>-,220/)/)'F,0-
%/2'-,7,)'.0),/<'F,-(D=I,0'F,-'(->,',+'F,-(D=/-7F,%/'F,-(D=8H/-1/'F>-/&D2I0<)/
'022&,02(;(0.(1.,I(10/D2=:0..1,(--()>,+D-0/-'/'-,('%,)'/)2'&+=</-'F,2,()(.=2,28
m('0,)'2:0..F(;,'F,/D'0/)'/F(;,1.//++-(:)</-1.//+E1(2,+10/%(-i,-2I0)7.&+0)>
D-/<0.0)>/<D.(2%(7='/i0),()+()>0/>,)07<(7'/-2()+70-7&.('0)><-,,D.(2%(n3gI(2
+,27-01,+0)2,7'0/)o8p8B8
mF(-%(7/i0),'07()(.=2,2:0..(.2/1,D,-</-%,+(2+,27-01,+0)2,7'0/)o8B8
qQrstuvwt^vxvTtuyw
qQz
vX[e[{[X[Z|TV[ZWV[Y
}8p8p m('0,)'2%&2'F(;,F02'/./>07(..=/-7='/./>07(..=7/)<0-%,+2'(>,O)/)E2%(..7,...&)>
7()7,-I/--,7&--,)')/)E2%(..7,...&)>7()7,-:F07F02)/'(%,)(1.,'/7&-('0;,0)',)'
'F,-(D=8
}8p8B m('0,)'2%&2'F(;,%,(2&-(1.,+02,(2,1=A@5O4Jp8p7-0',-0(
}8p8} H/-@GHA%&'()'7/F/-'ID('0,)'2%&2'F(;,
 n/7&%,)',+@GHA%&'('0/)1=56OgE7,-'0<0,+',2'
 n/7&%,)',++02,(2,D-/>-,220/)/)'-,('%,)':0'F,-./'0)01I>,<0'0)01I(<('0)01I/-/'F,-
@GHAE'(->,',+'=-/20),i0)(2,0)F010'/-
 J022&,(;(0.(1.,<-/%(10/D2=/-2&->07(.D-/7,+&-,D,-</-%,+(<',-D-/>-,220/)/)()
@GHA'(->,',+'=-/20),i0)(2,0)F010'/-8O<'022&,02)/'(;(0.(1.,I'F,D('0,)'%&2'F(;,
10/D2=(77,2201.,+02,(2,()+%&2'1,:0..0)>'/&)+,->/(10/D2=8
L
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
&'(') +,-./012345647,8,-49:54;<64=23=485><?
@ A,732<64<B./0123454;,6CDEFGHI7<-4;J;<B4<=4
@ A,732<64<BB;=<5=<:-,K-<==;,6,64-<542<64L;48<-M,4;6;C9K<J;4;6;C95J54;6;C9,-,48<-
/N+0I45-K<4<B4D-,=;6<O;65=<;68;C;4,-
@ P;==3<5>5;M5CM<J,MM,L;6K:-,K-<==;,6,62,=4-<7<64=D=4<2;748<-5:D'GJ4;==3<;=6,4
5>5;M5CM<948<:54;<6423=485><C;,:=D577<==;CM<B;=<5=<56B23=4C<L;MM;6K4,36B<-K,
5C;,:=D'
&'('Q HK<R(SD<5-='
&'('T /EUN:<-J,-2567<=4543=V1
&'('W HC;M;4D4,45O<:;MM=CD2,348
&'('S X54;<64=23=485><6,-25M,-K5656B25--,LJ3674;,65=B<J;6<BC<M,L?
Y M<3O,7D4<=
R&9[[[\27F
Y 5C=,M34<6<34-,:8;M7,364
R(9Q[[\27F
Y 8<2,KM,C;6
R]K\BF
Y 4,45MC;M;-3C;6
V^_`bcdefcfgfchdijgkklmjcncfhodhmnijpqrst
Y HuPvuNUPw\HFPvuNXPw V1'QxqrshmV`bqrsconlfiefielefhfyljczlm
Y 7-<54;6;6<7M<5-567<
R)Q2F\2;6
&'('] X54;<64=L;485=D2:4,254;7C-5;62<45=45=<=5-<5MM,L<B95=M,6K5=48<D5-<=45CM<56B
B,6,4-<{3;-<4-<542<64L;48564;7,6>3M=564=,-<=75M54;6KB,=<=,J=4<-,;B='|5};232
B5;MDB,=<,J=4<-,;B==8,3MBC<:-<B6;=,6<1[2K,-<{3;>5M<64'05B;54;,648<-5:DJ,-
C-5;62<45=45=<=23=4C<7,2:M<4<B54M<5=4()B5D=:-;,-4,4-<542<64,6:-,4,7,M'
&'('([P8<<JJ<74=,J;C-34;6;C,648<B<><M,:;6K83256J<43=5-<36O6,L6'~,2<6,J78;MBI
C<5-;6K:,4<64;5M56B2<623=45K-<<4,3=<8;K8MD<JJ<74;><7,64-57<:4;,6v;J3=;6K
8,-2,65MC;-487,64-,M23=45BB5=<7,6BC5--;<-2<48,B5C=4;6<67<w:-;,-4,=43BD
<64-D9J,-48<B3-54;,6,J=43BD:5-4;7;:54;,65=L<MM5=J,-54M<5=4(2,6485J4<-48<M5=4
B,=<,J;C-34;6;C'u8,3MB5L,256C<7,2<:-<K6564,-=3=:<74=8<;=:-<K6564L8;M<=8<
,-8<-:5-46<-;=:5-4;7;:54;6K;648;==43BD9=8<=8,3MB;6J,-28<-4-<54;6K:8D=;7;56
;22<B;54<MD'|<64-<54<B,-<6-,MM<B,648;=:-,4,7,M23=45M=,5K-<<4,3=<8;K8MD
<JJ<74;><7,64-57<:4;,6:-;,-4,48<=43BD9J,-48<B3-54;,6,J=43BD:5-4;7;:54;,656B&
2,648=5J4<-7,2:M<4;,6,J;C-34;63C5B2;6;=4-54;,6'
&'('((HC;M;4D4,36B<-=456B56B48<L;MM;6K6<==4,=;K65L-;44<6;6J,-2<B7,6=<64B,732<64'


([
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'&( *+,-./,02343+5.6.7.-5.89:;<,=640-/.>-/+0.-/3-?-,4602-,3-/@'34A604B-/-,-+,-4/
4B0,A8=,6.+,C./,D46,6.+,C./,2-,34,3.6+/,-E7+/7.6+F./,02-,3-/'(8+=04B0,A8=
,6.+,C./,
%&'&' *6-46,6.+,C./,2-,3-?6A,-/-?
%&'&% G/42/3=H.60./0-,-5-,=,4-?6A,-/-?
%&'&I J4/7A66./,A0.4B+F./,0,3+,0,64/FK=-/3-?-,46-/8A7.JL*%MA/K.00A0.-0+HH645.8?=
,3.C.8-7+KC4/-,46N0..0.7,-4/I&I&'&(B468.,+-K06.F+68-/F0H.7-B-7+F./,0O&
%&'&P Q/74/,64KK.8-/,.67A66./,-KK/.00-/7KA8-/FD?A,/4,K-C-,.8,4D4/F4-/F46+7,-5.-/B.7,-4/D
0=CH,4C+,-774/F.0,-5.3.+6,B+-KA6.DA/0,+?K.+/F-/+H.7,46-0D7+68-+7+663=,3C-+D46
H0=73-+,6-7-KK/.00R047-+K0-,A+,-4/0,3+,24AK8K-C-,74CHK-+/7.2-,30,A8=6.SA-6.C./,0&
%&'&T *6.F/+/,+/8/A60-/F24C./&
%&'&@ *+,-./,02-,3+3-0,46=4B+/4,3.6+7,-5.C+K-F/+/7=2-,3-/,3.H+0,,24=.+60D2-,3,3.
.U7.H,-4/4B/4/EC.K+/4C+7A,+/.4A0C+K-F/+/7=D7.65-7+K7+67-/4C+-/0-,AD468A7,+K
7+67-/4C+-/0-,A23-733+0?../0A77.00BAKK=,6.+,.82-,37A6+,-5.-/,./,,3.6+H=&
%&'&V M/=F+0,64-/,.0,-/+K8-0468.6.UH.7,.8,4K-C-,+?046H,-4/4B-?6A,-/-?
%&'&W X6.+,C./,2-,32+6B+6-/464,3.65-,+C-/G+/,+F4/-0,&*+,-./,02-,3A0-/F2+6B+6-/234
02-,73,4+/4,3.6B46C4B+/,-74+FAK+,-4/2-KK?..K-F-?K.&
%&'&(Y*+,-./,02-,3H.60-0,./,+/8A/74/,64KK.8+,6-+KB-?6-KK+,-4/&
Z[]^_`]a_b]de`b
Z[f
ghijkglmnop
((
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$

&'(
*+,-/,012134+515678-53769454,3:134+5
;<=>?@=A?BCDDE=>F@CACG?=<=FHA>AHI?J>?C=A?E>GCGKLHCAM=G?CN>?CHA>DH<OH@@=<OC>D>N=A?G
H<?P=<>JC=GH?P=<?P>A?PHG=F=GO<CE=FE=DHB@>QE=>F@CACG?=<=FBC?P?P=CA?=A??H?<=>??P=
J>?C=A?R
G@>DCNA>AOQK
SHG==GO>D>?CHABCDDJ<HO==FEQ?P=THDDHBCANJD>AU
*+,-V-W-2
XY:Z3454Y*+,-
[\
\]^@N_`F>CDQ
[a
b\^@N_`F>CDQ
^[c?><?CANSHG=
de^@N_`F>CDQ
a
]b^@N_`F>CDQ


fg>G=DCA=C@>NCANG?IFC=G>AF?I@H<
@=>GI<=@=A?G
f`J?CHA>DOHDD=O?CHAHTEDHHFTH<ECH@><h=<G
f;CGGI=J<HOI<=@=A?i><OPCM>DH<A=Bj
_>?C=A?GBC?P<=OI<<=A?k@=?>G?>?COLclml
f
nO?CM>?CANopqr@I?>?CHAJ<=G=A?
f
_<HN<=GGCHAHAopqr?><N=?=F
?Q<HGCA=hCA>G=CAPCEC?H<


SHG=oGO>D>?CHAUc?><?CANBC?PCE<I?CACE
de^@N_`F>CDQ
SHG=osJ>AGCHAUt;SH<CE<I?CACE]b^
@N_`F>CDQ


_<HN<=GGCM=SCG=>G=
c?HJCE<I?CACE>AFHTT
G?IFQ


r=GJHAG=H<c?>ED=SCG=>G=
lHA?CAI=CE<I?CACEIA?CD
J<HN<=GGCHAH<CA?HD=<>ED=
GCF==TT=O?G
nGG=GG<=GJHAG==M=<Q]
B==hGiuk[vF>QGj
a\
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'(*+,+-+./-&0+1+-23%456+'7(8+.(7+.9(1-+&.:;<=.7>+**?((@=*A=-(7=8-(B-C(1&,D*(-+&.
&8E21*(FGHDD*2+./-C(IJI7('+/.K-C(8+B'-1&C&B-&8ID=-+(.-'>+**?(-B(=-(7=-7&'(*(@(*
LGM(>1&C&B-'&8D=-+(.-'>+**.&-?(-B(=-(7A.-+*-&0+1+-2C='?((.(@=*A=-(78&B=**1ABB(.-
D=-+(.-'G5C(=*/&B+-C,+'='8&**&>'N3F6O8L&A-&8ID=-+(.-'(0D(B+(.1('%45K-C(.(0-1&C&B-
&8ID=-+(.-'>+**?(-B(=-(7=--C(.(0-C+/C(B7&'(*(@(*G3P6O8F&A-&8ID=-+(.-'7(@(*&D'%45K
=77+-+&.=*ID=-+(.-'>+**?(-B(=-(7=--C('=,(7&'(*(@(*GO8.&,&B(%457(@(*&D'=--C(7&'(K
+G(GF&A-&8=-&-=*&8QD=-+(.-'7(@(*&D'%45K-C(7&'(('1=*=-+&.1&.-+.A('-&.(0-C+/C(B*(@(*
8&B=1&C&B-&8ID=-+(.-'G3I6H-=.2/+@(.7&'(K+8,&B(-C=.F&A-&8ID=-+(.-'&BQD=-+(.-'
(0D(B+(.1(%45K-C(7&'(*(@(*(01((7'-C(R5%=.7ID=-+(.-'>+**?(-B(=-(7=--C(.(0-*&>(B
7&'(*(@(*+8-C(B(=B(*(''-C=.QD=-+(.-'=*B(=72-B(=-(7=--C=-7&'(GO8-C+'+'-C(*&>('-7&'(
*(@(*-('-(7K-C(-B+=*>+**?(-(B,+.=-(7=.7R5%+'.&-8&A.7GS&**&>+./-C(=?&@('1C(,(K
R5%+'7(8+.(7='-C(C+/C('-7&'(*(@(*+.>C+1CQD=-+(.-'C=@(?((.-B(=-(7>+-C=-,&'-F
+.'-=.1(&8%45GT+@(.-C('(7&'(*(@(*'=.7QD=-+(.-'-B(=-(7=-R5%K+-+'=.-+1+D=-(7-C=-AD
-&PU(*+/+?*(D=-+(.-'=B(B(VA+B(78&B-C(7&'(('1=*=-+&.D=B-&8-C('-A72G
5C(DB+.1+D=*+.@('-+/=-&B>+**(@=*A=-((=1C+.7+@+7A=*1&C&B->+-C+.=7&'(*(@(*=.7,=W(=
B(1&,,(.7=-+&.B(/=B7+./7&'(('1=*=-+&.&B7(X('1=*=-+&.GO8-C(B(=B(P%45'+.%&'(4(@(*LK
%&'(4(@(*XF>+**?((.B&**(7GO8-C(B(=B(P%45'+.%&'(4(@(*XFK%&'(4(@(*XP>+**?(
(.B&**(7GO8-C(B(=B(P%45'+.%&'(4(@(*XPK-C((.B&**,(.->+**?('-&DD(78&B-C('-A72G5C(
R5%>+**?(7(8+.(7='-C(C+/C('-7&'(=->C+1CYF&8Q&8D=-+(.-'+.-C(1&C&B-(0D(B+(.1('=
'-A72-B(=-,(.-B(*=-(7%45G5C(,=0+,A,D*=..(77&'(+'ZUL,/[\7=+*2]+8-C+'7&'(+'
>(**-&*(B=-(7K+->+**?(A'(78&B-C(B(,=+.7(B&8-C('-A72G
^(8&B(=DD*2+./-C(7&'(('1=*=-+&.BA*('K=**D=-+(.-'+.&.(1&C&B-,A'-C=@(?((.(@=*A=-(78&B
-&0+1+-2G
\.1(-C(R5%C='?((.7(-(B,+.(7K-C(R5%1&C&B->+**?((0D=.7(7AD-&=-&-=*&8PL_TS`
,A-=.-D=-+(.-'K+.1*A7+./-C(D=-+(.-'(.B&**(78&B7&'(('1=*=-+&.K=.7ab_`P,A-=.-D=-+(.-'
8&**&>+./-C(T(C=.c'PX'-=/(%('+/.G

5C(,=0+,A,=11BA=*&8-C('-A72>+**?(UID=-+(.-'G
5C('-A727BA/>+**?(=7,+.+'-(B(7&.=1&.-+.A&A'?='+'&.PZ7=2121*('G[=-+(.-'>+**?(
+.'-BA1-(7-&-=W(-C('-A72,(7+1=-+&.=--C('=,(-+,((@(B27=2G
5C(D=-+(.->+**?(B(VA('-(7-&,=+.-=+.=,(7+1=-+&.7+=B2&8(=1C7&'(&8,(7+1=-+&.G5C(
,(7+1=-+&.7+=B2>+**?(B(-AB.(7-&1*+.+1'-=88=--C((.7&8(=1C121*(G
_0D+B(7=.7A'(7,(7+1=-+&.'>+**?(7('-B&2(7D(BR%H.7(B'&.+.'-+-A-+&.=*D&*+12G
:;<
efghihjhkikgekmfnohphjhiqrkshthjuveorw
5&0+1+-+('>+**?(7('1B+?(7=11&B7+./-&MEOXE5EH_@(B'+&.UGLG%&'(X*+,+-+./-&0+1+-2+'
7(8+.(7='-&0+1+-2-C=-+'D&''+?*2KDB&?=?*2K&B7(8+.+-(*2=--B+?A-=?*(-&-C('-A72B(/+,(.+.-C(
&D+.+&.&8-C(DB+.1+D=*+.@('-+/=-&B=.7-C=-+'N
x TB=7(I&BC+/C(B.&.XC(,=-&*&/+1-&0+1+-2(01*A7+./.=A'(==.7@&,+-+./=.7'W+.B='C
FI
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
% '()*+-.+/0(12+.3)45+6(37+.+/0(12+.3)41(8()*+-09(1:61;<012+.3)
% '()*+=1(9389+(.)/>+)).*?1:303.809)0;)..106+;1.0(177+*@3093.0@1@++A>@309
).03B+:+03;>
% '()*+->A3.()>9
C>).+D;+2031.43509+01D3;30<3>(+8)(*3.8)>6+3.821>>367<(+7)0+*0109+>0/*<(+83:+.6/03.
09+123.31.1509+2(3.;32)73.?+>038)01(3>5+70016+:1(+73A+7<(+7)0+*01);1.;/((+.0
:+*3;)031.409+/.*+(7<3.8:)738.).;<4);1B:1(63*;1.*3031.41(>1:+5);01(109+(09).09+
>0/*<(+83:+.409+2(3.;32)73.?+>038)01(:)<;911>+01.10(+8)(*30)>)EFG51(09+2/(21>+>
1509+>0/*<H
C.<EFG09)01;;/(>@3093.09+53(>0;<;7+1509+()2<IJK*)<>L@3776+/>+*01:)A+*+;3>31.>
)61/02(1;++*3.80109+>/6>+M/+.0;191(0H
NON
QRSRTUVXYSZY[\]US]^R_\ZU]\YS`abTYZR_cTR`aUS_dceeYT]\fRXUTRQc\_RV\SR`
-H-Hg h+(:300+*i1.;1:30).0j+*3;)031.>
k/221(03?+:+*3;)031.>3.);;1(*).;+@309>0).*)(*2();03;+I>/;9)>51(+:+>3>4
*3)((9+)4+0;HL)(+2+(:300+*Hl>+15.+/0(129378(1@095);01(>I5378()>03:).*
2+85378()>03:L1((+*6711*;+778(1@095);01(>I+(<09(1213+03.L3>2+(:300+*2+(
3.>030/031.)72173;<).*3.);;1(*).;+@30909+Ckim8/3*+73.+>H
gnG().>5/>31.>:)<6+
83?+.3.);;1(*).;+@3093.>030/031.)72173;<H
opqrsuqvrwxwyz{|}~wqwsxrq}srx~sxsqrqB;).;+((+7)0+*:+*3;)7(+)>1.>I+84
13.03.57)::)031.4)>09:)+D);+(6)031.4()>94).03+:+03;/>+).*3.5/>31.(+);031.>L)0
*1>+>09)0*1.10+D;++*g:82+(*)<152(+*.3>1.+1(+M/3?)7+.0)(+2+(:300+*H
G9+51771@3.8:)<6+;1.>3*+(+*71;)73+*91(:1.)71(61.+>2)(3.80(+)0:+.051(.1.B
B;+77:)738.).;3+>4).*71;)73+*()*3109+()2<51(:+*3;)7;1.*3031.>109+(09).09+
/.*+(7<3.8B;+77:)738.).;3+>H
-H-HJ j+*3;)031.>016+l>+*@309i)/031.
-H-HJHg
ih=CB.936301(>.*/;+(>
6(/03.363>:+0)6173+*2(3:)(37<6<ih=CHC?13*;1B)*:3.3>0()031.@309>0(1.81(
:1*+()0+ih=C3.936301(>).*;1.>3*+()70+(.)03?+)8+.0>@3097+>>ih=C
3.9363031.Hi1B)*:3.3>0()031.15A+01;1.)17+4)>0(1.8ih=C3.936301(43.gK
9+)709<>/6+;0>3.;(+)>+**1>+.1(:)73+*+D21>/(+4i:)D).*CliB7)>041536(/03.36
6<JnB).*J-B517*4(+>2+;03?+7<HG9+:)D3:)716>+(?+*36(/03.36+D21>/(+ICliL
~wzB517*3.=2)03+.0>0(+)0+*@309:37*).*1(:1*+()0+ih=C3.936301(>@9+.
;1:2)(+*@30909+36(/03.36+D21>/(+3.2)03+.0>.100(+)0+*;1.;1:30).07<@309
ih=C3.936301(>Hi73.3;)7>)5+0<*)0)3.2)03+.0>0(+)0+*@309:1*+()0+I.-L1(
>0(1.8ih=C3.936301(>I.gnL*3*.10(+?+)7:+).3.85/73.;(+)>+>3.01D3;303+>H
k0(1.83.936301(>15ih=CI+84A+01;1.)17+43.*3.)?3(4.+753.)?3(4(301.)?3(4
g-
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()*&+),-/0&,)12,345/)*-160)12,345/)*-)1,&/3*&7306-&*8*69&7&83*6:%23(08;6
&+3)868<=9&%1,3*>?@ABC)*2);)13,4(%1;6(%68-/3*%)86,,68(/)*>);,(1)*);83%6
13DEF4>3,G)1223081,6&146*1164H3,&,)05<I(;J6/1%%23(08;643*)13,6893,%)>*%
39);,(1)*);13K)/)15<=9126;6*69)13(1G6)>2%126,)%L&*8&4386,&16?@ABC
)*2);)13,4(%1;6(%68-43*)13,%(;J6/193,13K)/)15&*893003G83%6438)9)/&1)3*
>()8&*/6&%*66868<C+3)8>,&H69,()1&*8I6+)0063,&*>6%8(,)*>);,(1)*);1,6&146*1-
&%126%6/3*1&)*4386,&16)*2);)13,%39?@ABC<
?3M&84)*)%1,&1)3*39);,(1)*);G)12%1,3*>?@ABC)*8(/6,%-,)9&4H)*-)*26&0125
%(;J6/1%86/,6&%6);,(1)*);H0&%4&/3*/6*1,&1)3*%;5&HH,3K)4&1605DFM9308<C+3)8
/3*/34)1&*1(%639%1,3*>?@ABC)*8(/6,%N6>-/&,;&4&76H)*6-,)9&4H)*-H26*513)*-
&*8I1<O32*P%Q3,1:<?3*%)86,&016,*&1)+6&>6*1%G)1206%%?@ABC)*8(/1)3*<
C/34H,626*%)+60)%139)*2);)13,%-)*8(/6,%-&*8%(;%1,&16%4&5;693(*8&1
211HRSS468)/)*6<)(H()<68(S/0)*H2&,4S88)%S4&)*M1&;06ST2)%G6;%)16)%/3*1)*(&005
,6+)%68&*8%23(08;6/26/L689,6'(6*10593,(H8&16%<
E<E<U<U
W,(>%T2&1X&5Y&+6T26),A0&%4&?3*/6*1,&1)3*%C016,68;5=;,(1)*);
=*+)1,3%1(8)6%)*8)/&16812&1);,(1)*);)%*31&%(;%1,&1639AM>05/3H,316)*NAM>H:-;(1
)%&4)08)*2);)13,NG)12&*=?ZF[\^_`abcdefg_=;,(1)*);)%*316KH6/168132&+6
%5%164)/8,(>M8,(>)*16,&/1)3*%G)12AM>H%(;%1,&16%<Y3G6+6,-)1/&**31;66K/0(868
12&1);,(1)*);/3(08)*2);)1)*16%1)*&0AM>H&916,&126,&H6(1)/83%6<T26,6)%*3/0)*)/&0
8&1&&+&)0&;06h126,693,6-/3M&84)*)%1,&1)3*39*&,,3G126,&H6(1)/)*86KAM>H
%(;%1,&16%N6>-8)>3K)*:G)12);,(1)*);4&5)*/,6&%6126),;0338/3*/6*1,&1)3*&*8
%23(08;6(%68G)12/&(1)3*&*843*)13,68/03%60593,13K)/)15<
E<E<U<B
iTA,303*>)*>C>6*1%
C*5468)/&1)3*%L*3G*13/&(%6iTH,303*>&1)3*%23(08;6(%68G)12/&(1)3*h
H6,)38)/j?k&*8606/1,3051643*)13,)*>%23(08;6/3*%)86,68<
E<E<U<E
C*1)H0&16061C>6*1%&*8C*1)/3&>(0&*1%

Q&,9&,)*3,+)1&4)*l&*1&>3*)%1%%23(08*31;6&84)*)%16,68/3*/34)1&*105G)12
);,(1)*);<I(HH0646*1%%(/2&%9)%23)0&*8+)1&4)*jH,6H&,&1)3*%%23(08;6&+3)868<
m%6);,(1)*);G)12/&(1)3*)*%(;J6/1%,6'(),)*>3126,&*1)/3&>(0&*1%3,468)/&1)3*%
12&1)*2);)1H0&160619(*/1)3*<I(;J6/1%G)12/3*>6*)1&0;0668)*>8)&126%)%2&+6*31
;66*%1(8)68<=;,(1)*);%23(08;62608&106&%1B13n8&5%H,6M&*8H3%1M%(,>6,5
86H6*8)*>(H3*12615H639%(,>6,5&*8126,)%L39;0668)*>N%66I6/1)3*o<U:<

I(;J6/1%,6'(),)*>126)*)1)&1)3*39126,&H6(1)/&*1)/3&>(0&1)3*126,&H5N3126,12&*
G&,9&,)*3,&+)1&4)*l&*1&>3*)%1:8(,)*>126/3(,%639126%1(85%23(082&+6
1,6&146*1G)12);,(1)*);SH0&/6;32608-126%H3*%3,P%468)/&043*)13,%23(08;6
DZ
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()%(*+,)'+./01(.'./234)%*/&56&14+'&(/*0*5()0(*+1'(.4(6*51/7*%(.5%4.'.%)448
5()/4*)'+(6*0*9.'.(.)(.&'&:./01(.'./234)%*/&.5)330&;*+/8(6*53&'5&0<5=*+.%)4
=&'.(&0>?1/7*%(556&14+/*&/5*0;*+%4&5*48:&05.@'5)'+58=3(&=5&:/4**+.'@>
A&+&5*0*+1%(.&'.50*B1.0*+C6*'5(1+8+01@.50*5()0(*+>
D>D>E G0&6./.(*+H&'%&=.()'(I*+.%)(.&'5
J'8%6*=&(6*0)38,)'(.%)'%*0.==1'&(6*0)38,*K3*0.=*'()4(6*0)38,&00)+.&(6*0)38.5
30&6./.(*+C6.4*(6*51/7*%(.50*%*.;.'@./01(.'./(0*)(=*'(>
H&0(.%&5(*0&.+5:&0(6*(0*)(=*'(&:(6*1'+*048.'@+.5*)5*)0*30&6./.(*+>H&0(.%&5(*0&.+5
:&0(6*(0*)(=*'(&:'&'9%)'%*00*4)(*+0*)5&'5:&04&'@*0(6)'LD+)85)'+2&0)(+&5*5
MLNN=@&:30*+'.5&'*&0.(5*B1.;)4*'()0*30&6./.(*+>
O08(60&3&.*(.%@0&C(6:)%(&05P*@,*08(60&3&.*(.'Q)'+'*1(0&36.4@0&C(6:)%(&05P*@,
:.4@0)5(.=)'+3*@9:.4@0)5(.=Q)0*)45&30&6./.(*++10.'@(6*:.05(%8%4*&:(6*0)38C6.4*
RST5)0*/*.'@)55*55*+>
D>D>D U1.+*4.'*5:&0V/01(.'./I)')@*=*'(C.(6?10@*0.*5&0G0&%*+10*
V/01(.'./=)8.'%0*)5*0.5W&:/4**+.'@C.(6.';)5.;*30&%*+10*5&0510@*08>T6*
:&44&C.'@@1.+)'%*56&14+/*)334.*+(&(6*15*&:./01(.'./.'(6*3*0.&3*0)(.;*3*0.&+
:&03)(.*'(5C6&0*B1.0*510@.%)4.'(*0;*'(.&'&0)'.';)5.;*30&%*+10*C6.4*0*%*.;.'@
./01(.'./X
I.'&0?10@.%)4G0&%*+10*5
Y&0=.'&030&%*+10*5P51%6)5)%*'(0)44.'*34)%*=*'(,'**+4*/.&358,(6&0)%*'(*5.5,&0
3)0)%*'(*5.5Q./01(.'./56&14+/*6*4+:&0)(4*)5(E+)8530.&0(&(6*30&%*+10*)'+56&14+
'&(/*0*5()0(*+:&0)(4*)5(E+)85):(*0(6*30&%*+10*>Y&0/&'*=)00&C/.&35.*5(6)()0*
3*0:&0=*+C6.4*(6*51/7*%(.5&'./01(.'./,.(.5'&('*%*55)08(&6&4+./01(.'./:&0(6*5*
30&%*+10*5>
I)7&0?10@.%)4G0&%*+10*5
Y&0)'8510@*08&0.';)5.;*30&%*+10*0*B1.0.'@51(10*5&05()34*5:&0%4&510*,./01(.'./
56&14+/*6*4+)(4*)5(Z+)8530.&0(&(6*.'(*0;*'(.&')'+56&14+/*6*4+)(4*)5(Z+)85
):(*0(6*30&%*+10*)'+0*5()0(*+)((6*+.5%0*(.&'&:(6*.';*5(.@)(&0C6*'(6*510@.%)4
5.(*.50*)5&')/486*)4*+C.(6&1(5*0&5)'@1.'*&15+0).')@*&0(6*'**+:&0+0).')@*
(1/*5>
D>D>D>L
O=*0@*'%8G0&%*+10*5
L[
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&')*)'+),-./'&-)01')2345'164,4527&1805)7)809:6)'67)/'&-)01')1,64867)
21'+4-98246)42')92&,958.7)98)03:&'968)926;09.29:6)'67)1'+),621'+4-98
/'&-)01')<
=>?
ABCDEFGHGJKLMCDNO
P,67)952),-)&:6')96*),60)89.201)6&90Q)'2))Q),6R2S36')96*),6*9.-&,64,1)1,648&,)&:
67):&88&T4,+-'46)'499//84)2U
V X42)92)/'&+')224&,3
V P,6)'-1''),6488,)226796/')Q),62:1'67)'90*4,426'964&,&:6')96*),63
V Y,9--)/6958)90Q)'2))Q),6R2S3
V Z964),6,&,[-&*/849,-)3
V Z964),60)-40)26&T4670'9T:'&*67)2610.3&'
V \),)'98&'2/)-4:4--79,+)24,67)/964),6]
2-&,0464&,'),0)'67)/964),61,9--)/6958)
:&':1'67)'6')96*),64,67)^10+*),6&:67)4,Q)264+96&'<
=>_
ABCDEFGHGJ`GaaGbcN
Z964),62T4885):&88&T)0:&'d*&,6729:6)'')*&Q98:'&*2610.&'1,6480)9673T74-7)Q)'&--1'2
:4'26<e15^)-62')*&Q)0:'&*6')96*),6:&'1,9--)/6958)90Q)'2))Q),6R2ST4885):&88&T)01,648
')2&8164&,&'2695484f964&,&:67)90Q)'2))Q),6R2S<g7)2)/964),62T48867),32152)h1),68.5)
:&88&T)0:&'8&,+6)'*21'Q4Q98)Q)'.d*&,672<
=>i
jCFEMCFDJGCkMlGmDaJCGlnEBoO
Z964),62T4885)')*&Q)0:'&*2610.T7),9,.&:67)-'46)'498426)04,e)-64&,p<q9//84)2&'
/964),6428&266&:&88&T1/<g7)')92&,:&'2610.')*&Q989,067)096)67)/964),6T92')*&Q)0
*1265)0&-1*),6)04,67)r92)s)/&'6%&'*<
?>AtnuvwAxyz{n|Atnx}tAu`ujzKutvn
P,6)''1/645'164,4567)'9/.:&'9,.\'90)~&'+')96)',&,[7)*96&8&+4-986&4-464)23+'90)~&'
+')96)',)16'&/),49T4674,:)-64&,&':)Q)'3&'+'90)p7)*96&8&+4-986&4-464)2<,-)67)
2.*/6&*2&:67)6&4-46.79Q)')2&8Q)06&\'90)&'592)84,)345'164,45*9.5)')[4,46496)096
67)269'64,+0&2)<P:67)6&4-46.')&--1'23')01-)67)0&2)920)2-'45)04,67)6958)5)8&T<P:
67)2)6&4-464)2/)'2426&'')-1':&88&T4,+6T&0&2)')01-64&,2345'164,45T4885)/)'*9,),68.
042-&,64,1)0<
;
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
&'()**'+,',,)-'*),./.(01.)+-/)213'-'1)4.(.1.'-02','-(2.5',5'6)78
9:;<=<>?
A==BCCDE=D
F>GC><EHI:JDKLMNOHF>GC><EHI:JDKPQNOHF>GC><EHI:JDKMRNOH
S.2-1
&'-102101TUV*W,0.6X&'-102101YZV*W,0.6X&'-102101U[V*W,0.6X
\'()+,
YZV*W,0.6X
U[V*W,0.6X
[TV*W,0.6X
]3.2,
U[V*W,0.6X
[TV*W,0.6X
^UV*W,0.6X
S)_213
`.-()+1.+_'.52_1.+.5 `.-()+1.+_'.52_1.+.5 `.-()+1.+_'.52_1.+.5
`)-'2',_(1.)+-02'a'2*0+'+1)+('.*a6'*'+1',b
QceIfghFggfgi9FeiIhgjAh9kil
eIfghFggfgi9hgjAh9kil
].*'6Xm0((_201'm0+,()*a6'1'2'a)21.+W0+,0+06X-.-)/-0/'1X.+/)2*01.)+/2)*(6.+.(06-1_,.'-
02'(2_(.06/)213'a2)1'(1.)+)/-_5n'(1-m.+o'-1.W01)2-m0+,13'-a)+-)2m0+,02'*0+,01',5X
2'W_601)2X0W'+(.'-7)26,7.,'b
IDp<E<><:EJ
eqrDCJDgrDE>J
s+st.-0+X_+1)702,*',.(06)((_22'+('.+0a01.'+10,*.+.-1'2',0a302*0('_1.(06a2),_(1
0+,73.(3,)'-+)1+'('--02.6X30o'0(0_-062'601.)+-3.a7.1313.-12'01*'+1bs+st(0+
13'2'/)2'5'0+X_+/0o)2056'0+,_+.+1'+,',-.W+u.+(6_,.+W0(6.+.(066X-.W+./.(0+105+)2*06
605)201)2X/.+,.+Wm/)2'40*a6'vm-X*a1)*m)2,.-'0-'1'*a)2066X0--)(.01',7.1313'_-')/0+
.+o'-1.W01.)+06-1_,X,2_Wm73'13'2)2+)1()+-.,'2',2'601',1)13'-1_,X,2_Wuwxyzt[sm^{{Yvb
S)213'a_2a)-'-)/13.-(6.+.(06-1_,Xmst-.+(6_,''o'+1-73.(302''.13'2+'7)22'a2'-'+1
,'1'(1056''40('2501.)+-)/a2'z'4.-1.+W()+,.1.)+-b
]3'1'2*|,.-'0-'a2)W2'--.)+}-3)_6,+)15'2'a)21',0-0+0,o'2-''o'+11'2*bs-0+'40*a6'm
~7)2-'+.+W)/_+,'26X.+W,.-'0-'~)213'(6.+.(06,.0W+)-.-1301.-0--)(.01',7.13,.-'0-'
a2)W2'--.)+-3)_6,5'2'a)21',b
s,o'2-''o'+1-*0X.+(6_,'m5_102'+)16.*.1',1)8
 \_5n'(1.o')2)5n'(1.o'-X*a1)*-a2)o.,',5X13'a01.'+10+,)2)5-'2o',5X13'
w+o'-1.W01)2)2-1_,X-10//.+(6_,.+W605)201)2X05+)2*06.1.'-)/(6.+.(06-.W+./.(0+('b
 s+Xst-'4a'2.'+(',5X13'a01.'+1132)_W313'()*a6'1.)+)//.+06-1_,Xa2)(',_2'-b
^T
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
% '()+,-./012,3)45,6)0/1072+-80.9-20+--89-0:0/;073/2+;-80./,-,<,4=).0<2>207'(
/0.,/-2+;.0/2,7?2+<4372+;)2;+),/)5:.-,:)9)),<29-07@2-8-803+70/452+;72)09)0-89-
@0/0+,-./0)0+-60>,/0-80'(/0.,/-2+;.0/2,7
% A,:.42<9-2,+)-89-,<<3/9)9/0)34-,>./,-,<,4=:9+79-072+-0/10+-2,+)B0;?2+19)210
./,<073/0))3<89)62,.)20)CD
E80>,44,@2+;9/0FGE<,+)270/07'()H
% IJKLKMNOPNQRTUQVNPNUQW'./0=0X2)-2+;<,+72-2,+B7,<3:0+-07,+-80:072<9482)-,/5AYZC
2)+,-<,+)270/079+'(3+40))-80)010/2-5?>/0[30+<5?,/<89/9<-0/,>-80010+-@,/)0+)
73/2+;-80)-375.0/2,7D
% IJKL\]^QQKVUJK]KTPN_K`UO\NP^]Na^PNUQW'8,).2-942b9-2,+.49++0760>,/0)2;+2+;-80
2+>,/:07<,+)0+->,/:2)+,-<,+)270/079+c'(?63-/9-80/9-80/9.03-2<2+-0/10+-2,+D
d,@010/?2>73/2+;-80./0=.49++078,).2-942b9-2,+9+010+-,<<3/)?@82<8./,4,+;)-80
8,).2-942b9-2,+,/:00-)9+5,-80/c'(</2-0/29?-80010+-@24460<,+)270/079+c'(D
c3/;0/20),/2+-0/10+-2,+)-89-@0/03+70/<,+)270/9-2,+?63-+,-.0/>,/:0760>,/0
0+/,44:0+-2+-80)-375?@244+,-60<,+)270/07)0/2,3)2>-8059/0.0/>,/:079>-0/0+/,44:0+-
2+-80)-375>,/9<,+72-2,+-89-89)+,-<89+;07>/,:2-)69)042+040104D(40<-210
8,).2-942b9-2,+)>,/),<294/09),+)?),4045>,/-8097:2+2)-/9-2,+,><80:,-80/9.5?,/730-,
4,+;-/910472)-9+<0)9/094),+,-c'()D
% eN^RQUOPNTfKOPNQR^QVIJUTKVgJKOWE0)-2+;9+7./,<073/0))8,347+,--,60/0.,/-079)
'(),/c'()?63-/9-80/-80<93)0>,/-80-0)-,/./,<073/0)8,34760/0.,/-07D
% hOij\PUj^PNTfJK^PjKQPkK]^PKVlij\`UTiPUONOWE82)010+-)8,34794),+,-60
<,+)270/079+'(Dm9-20+-)@2-8-/09-:0+-=/049-0745:.8,<5-,)2))8,347/0:92+,+)-375
-/09-:0+-9+7<,+-2+30@2-8944)-375=/049-07./,<073/0)D
nKJNUgOhV_KJOKo_KQPO
'+9710/)0010+-,/)3).0<-079710/)0/09<-2,+2)<,+)270/07p)0/2,3)q2>?2+-80120@,>02-80/
-802+10)-2;9-,/,/-80).,+),/?2-/0)34-)2+9+5,>-80>,44,@2+;,3-<,:0)H
% r09-8
% '42>0=-8/09-0+2+;9710/)07/3;0X.0/20+<0s9+59710/)00X.0/20+<0-89-.49<0)-80
.9-20+-?2+-80120@,>-802+2-294/0.,/-0/?9-2::0729-0/2)t,>709-8>/,:-809710/)0
0X.0/20+<09)2-,<<3//07Du-7,0)+,-2+<43709+9710/)00X.0/20+<0-89-?8972-,<<3//07
2+9:,/0)010/0>,/:?:2;8-8910<93)07709-8D
% u+.9-20+-8,).2-942b9-2,+,/./,4,+;9-2,+,>0X2)-2+;8,).2-942b9-2,+
vw
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
% ')*+,-,.*/.0+,-1/-2-34/.-/34)43-.50+,67,.4/.-489-,+6).-0/02.:*47-8-.5.030/963.
/0+;488-2*26/3.-0/,<
% '30/1*/-.484/0;485=7-+.:9*2*3.<
>;)0+.4/.;*9-348*?*/.,.:4.;45/0.+*,68.-/9*4.:@7*8-2*A.:+*4.*/-/1@0++*B6-+*
:0,)-.48-C4.-0/;457*30/,-9*+*94,*+-06,49?*+,*9+61*D)*+-*/3*E:*/@74,*96)0/
4))+0)+-4.*;*9-348F691;*/.@.:*5;45F*0)4+9-C*.:*)4.-*/.0+,67F*3.4/9;45+*B6-+*
;*9-3480+,6+1-348-/.*+?*/.-0/.0)+*?*/.0/*02.:*06.30;*,8-,.*9-/.:-,9*2-/-.-0/<
GD4;)8*,02,63:;*9-348*?*/.,-/3869*488*+1-37+0/3:0,)4,;+*B6-+-/1-/.*/,-?*.+*4.;*/.-/
4/*;*+1*/35+00;0+4.:0;*@7800995,3+4,-4,0+30/?68,-0/,.:4.90/0.+*,68.-/-/)4.-*/.
:0,)-.48-C4.-0/@0+.:*9*?*80);*/.029+619*)*/9*/350+9+61476,*HIJKLMNJI<NIO<
PQRQSTUVXSTUQSTYZ[SY\Q]^_`
a*2-/-.-0/,206/9-/.:*K0;;0/b*+;-/08015K+-.*+-420+'9?*+,*G?*/.,?*+,-0/c<d
HKbK'G?c<dOE-887*6,*920+1+49-/1.:*,*?*+-.5H-/.*/,-.5O02'G,<b:*KbK'G?c<d
9-,)845,e+49*,J.:+061:fE-.:6/-B6*38-/-3489*,3+-).-0/,02,*?*+-.520+*43:+*2*+*/3*9'G<
g:06894)4.-*/.*D)*+-*/3*4/5'G/0.8-,.*9-/.:*KbK'G?c<d@.:*20880E-/11+49-/1,5,.*;
,:06897*6,*9.04,,*,,,*?*+-.5h
% e+49*JHi-89'GOj*D)*+-*/3*,E:-3:4+*6,64885.+4/,-*/.@+*B6-+-/1/0,)*3-48.+*4.;*/.@
4/9/0.-/.*+2*+-/1E-.:.:*)4.-*/.k,94-8543.-?-.-*,
% e+49*IHi09*+4.*'GOj*D)*+-*/3*,E:-3:-/.+0963*,0;*8*?*802-/30/?*/-*/3*0+
30/3*+/.0.:*)4.-*/.@4/9E:-3:;45-/.*+2*+*E-.:94-8543.-?-.-*,@76.4+*6,64885
4;*8-0+4.*975,-;)8*.:*+4)*6.-3;*4,6+*,
% e+49*NHg*?*+*'GOj*D)*+-*/3*,E:-3:4+*6/433*).478*0+-/.08*+478*@,-1/-2-34/.85
-/.*++6)..:*)4.-*/.k,6,64894-8543.-?-.5@4/9+*B6-+*,5,.*;-39+61.:*+4)50+0.:*+
.+*4.;*/.
% e+49*cHl-2*A.:+*4.*/-/10+9-,478-/1'GOj*D)*+-*/3*,E:-3:346,*.:*)4.-*/..07*-/
-;;-/*/.94/1*+029*4.:
% e+49*fHa*4.:+*84.*9.0'GOj*D)*+-*/3*,E:-3:+*,68.-/)4.-*/.9*4.:
XYmnYoTUVZpUUSTqmUTrs`
b:*>/?*,.-14.0+-,.04,,*,,.:*346,48+*84.-0/H-*@E:*.:*+.:*+*-,4+*4,0/478*)0,,-7-8-.5.:4.
.:*,.6959+61346,*9.:**?*/.O6,-/1.:*20880E-/19*2-/-.-0/,h
Id
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&')*+,'*-.
/012345789:41;234/<=:>154?@89:=A@4B824>?158@:4C94074
780012A44:28A@=:34DE=2323410:421;234/<80D8D>=0=:2582=101;
234=0F4:2=G82=108@?51D972B15H8789:8@54@82=10:3=?=:710:=D454D
A=1@1G=78@@I=>?@89:=A@4J
KL+MN*+O.
P347955402Q01E@4DG415=0;15>82=108A192234/<=0D=7824:23828
54@82=10:3=?21234=0F4:2=G82=108@?51D972=:90@=Q4@IJ
R&SSMT+O)*+,'*-.
P3454=:87@=0=78@@I?@89:=A@42=>4:4C94074A42E44010:421;234
/<80D8D>=0=:2582=101;234=0F4:2=G82=108@?51D972HA92234/<
719@D8@:1A48225=A924D2171079554021590D45@I=0GD=:48:4H15234
9:41;12345D59G:15?5174D954:JU1::=A@I54@824D:319@DA49:4D
E340234=0F4:2=G82=108@?51D972=:1041;:4F458@A=1@1G=78@@I
?@89:=A@4/<789:4:J
)*+,'*-.
P34/<=:7@485@I54@824D219:41;234=0F4:2=G82=108@?51D972J
KL*VW*X'*-Y-Z*[S*\Z*L'S
/0]904^?4724D_/<=:80/<2382=:012@=:24D=0234`0F4:2=G8215a
:b5173954c?87Q8G4=0:45215=:
012@=:24D82234:?47=;=7=2I15:4F45=2I238238:A4401A:45F4DJd154^8>?@4H34?82=704751:=:
E19@DA4]904^?4724D_eAIF=52941;G548245:4F45=2If=;234`0F4:2=G8215a
:b517395454;4554D10@I
214@4F824D34?82=740gI>4:1534?82=2=:Jh=>=@85@IH7454A58@2351>A14>A1@=:>80D7454A58@
F8:79@=2=:E19@DA4]904^?4724D_eAIF=52941;G548245:?47=;=7=2If=;234`0F4:2=G8215a
:
b5173954c?87Q8G4=0:452@=:24D10@I7454A58@F8:79@85877=D402:Jij04^?4724Di8@:154;45:21/<:
2382854>402=104D=0234`0F4:2=G8215a
:b51739548:177955=0GE=2387@8::1;D59G:158:
802=7=?824D;51>234?385>871@1G=78@?51?452=4:1;234D59GHA92854012:?47=;=78@@I>402=104D
8:177955=0GE=23234:29DID59G90D45=0F4:2=G82=10J
k&Xlm*L'MLn,L-)*W&['MLn&oY-Z*[S*\Z*L'S,L-p*[M&lSY-Z*[S*\Z*L'STO
qLZ*S'Mn,'&[S
YSS*SSm*L'&oY-Z*[S*\Z*L'S
`0F4:2=G8215:E=@@8::4::23417795540741;8DF45:44F402:80D:45=19:8DF45:44F402:828@@
:9Ar4724F8@982=102=>4?1=02:D95=0G234:29DIJ/@@8DF45:44F402:80D:45=19:8DF45:44F402:
E342345F1@9024454DAI234:9Ar472HD=:71F454DAI:29DI?45:1004@D95=0GC94:2=10=0GHD424724D
23519G3?3I:=78@4^8>=082=10H7@=0=78@@I:=G0=;=7802@8A158215I24:2H1512345>480:HE=@@A4
54715D4DJ<87354715D4D8DF45:44F40215:45=19:8DF45:44F402E=@@A4D4:75=A4DAI=2:D9582=10
e=4H:285280D40DD824:fH:4F45=2IH54G9@8215I:45=19:04::75=245=8e=;8??@=78A@4fH:9:?4724D
54@82=10:3=?21234=0F4:2=G82=108@?51D972H80D80I872=10:28Q40J
st
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()*(,'(-./(01).2-34()21&
566589:;<=;<>9<>?@A9@>B@BC9<>?@A9D:?66E<FGH=A><IJ>@K=;<=?K<9?LB<IGBIIG=<IMNO?9
@E=G?B<IAB=?6PQIGR9J@66@:?BL=;<6G9=I@9<@J9=AIRI>ALS
T<>?@A9GIU<>9<<U<B=9><H@>=<IGJ=<>PQIGR9J@66@:?BL=;<6G9=I@9<@J9=AIRI>AL9;@A6IG69@E<
><H@>=<I?JF@B9?I<><I><6G=<I=@9=AIRI>ALSV<9@6A=?@B?BJ@>KG=?@BGJ=<>PQIGR99;@A6IE<
H>@U?I<IS
W>@L><99?U<I?9<G9<9;@A6IXYZE<><H@>=<IG9GB<U<B==<>KDEA=?B9=<GI9RKH=@K9[F6?B?FG6
9?LB9@JI?9<G9<H>@L><99?@BKGRE<><H@>=<IS
566\>GI<P]^GIU<>9<<U<B=9D><LG>I6<99@J9<>?@A9B<99D9<U<>?=RD@>H><9AK<I><6G=?@B9;?H=@
9=AIRI>ALDKA9=E<><F@>I<IA9?BLK<I?FG6=<>K?B@6@LR?B=;<9@A>F<I@FAK<B=S566><F@>I9:?66
B<<I=@FGH=A><=;<I<=G?69@J=;<IA>G=?@BGBI=;<9<U<>?=R@J<GF;<H?9@I<D=;<GF=?@B=G_<B:?=;
><9H<F==@=;<9=AIRI>ALD?BU<9=?LG=@>`9<UG6AG=?@B@J?=9><6G=?@B9;?H=@=;<9=AIRI>ALDGBI=;<
<U<B=@A=F@K<Sa;<B<U<>H@99?E6<DI?GLB@9<99;@A6IE<L?U<B:;<B9?LB9GBI9RKH=@K9G><IA<
=@GF@KK@B<=?@6@LRb<LDF@AL;D>ABBRB@9<D9B<<c?BLD9@><=;>@G=DGBI;<GIF@BL<9=?@B9;@A6I
E<><H@>=<IG9dAHH<>><9H?>G=@>R?BJ<F=?@BdeS
566I<G=;99;@A6IE<><H@>=<I:?=;=;<H>?KG>RFGA9<@JI<G=;G9=;<58=<>KDG9I<G=;?9
=RH?FG66R=;<@A=F@K<@J=;<<U<B=DB@==;<<U<B=?=9<6JS
MJGI<G=;@FFA>9:?=;?BPQIGR9GJ=<>=;<6G9=I@9<@J9=AIRI>ALD=;<I<G=;KA9=E<><H@>=<IG9G
9<>?@A9GIU<>9<<U<B=S
T<>?@A95IU<>9<8U<B=V<H@>=?BLbT58eV<H@>=?BL
MKH@>=GB=K<I?FG6<U<B=9KGRG69@E<F@B9?I<><I9<>?@A9GIU<>9<<U<B=9S
f 566<U<B=9@FFA>>?BLIA>?BL=;<F@BIAF=@JGH>@=@F@6GBIK<<=?BL=;<I<J?B?=?@B@JGT58
KA9=E<><H@>=<I=@=;<MVh?BGFF@>IGBF<:?=;=;<=?K<J>GK<9GBIH>@F<IA><9@A=6?B<I
?BiZ;<jB?U<>9?=R@JZ<kG9lSmS5BI<>9@BNGBF<>N<B=<>MB9=?=A=?@BG6V<U?<:h@G>I
W@6?FRJ@>MBU<9=?LG=@>9@BV<H@>=?BLT<>?@A9jBGB=?F?HG=<I5IU<>9<8U<B=9J@>m>AL9
GBIm<U?F<9nS
f T<>?@A9GIU<>9<<U<B=9:?66E<FGH=A><IJ>@K=;<=?K<@J=;<J?>9=H>@=@F@6C9H<F?J?F
?B=<>U<B=?@BDAB=?6PQIGR9GJ=<>=;<6G9=I@9<@JI>ALDAB6<99=;<HG>=?F?HGB=:?=;I>G:9
F@B9<B=ST<>?@A9GIU<>9<<U<B=9KA9=E<J@66@:<IAB=?6F6?B?FG6><F@U<>R?9F@KH6<=<GBI
6GE@>G=@>R=<9=9;GU<><=A>B<I=@EG9<6?B<DH>@L><99?@B@J=;<<U<B=;G99=GE?6?c<ID@>=;<><
;G9E<<BGFF<H=GE6<><9@6A=?@B@J=;<<U<B=S
oo
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&()&*+,+)-./)(0(1(&2.3&*+4%5/6&*+,+)+5,7*&+58&.+/)9,+)+,(.9)56:+,)++:+/&)5,+
,+-.,&+6577.,6(/;&.&*+<.6+.3=+6+,51>+;915&(./)?@..6<1(/(7514,57&(7+)?&*+-,.&.7.1
;9(6+1(/+)?&*+)-./).,A);9(6+1(/+)?5/6%/)&(&9&(./51>+:(+BC.5,6-.1(72D
EFGHIJIKL
C+3.,+)&962+/,.118+/&?)90N+7&)89)&5;,++&.&5O+5--,.-,(5&+8+5)9,+)&.5:.(6-,+;/5/72D
P.B+:+,?)*.9165-,+;/5/72.779,(/53+851+)&962)90N+7&?7./)+/&&.-,.:(6+3.11.BQ9-
(/3.,85&(./,+;5,6(/;&*+.9&7.8+.3&*+-,+;/5/725/6&*+*+51&*.3&*+(/35/&9/&(1RS652).16
B(110+,+T9+)&+6D
U3+851+)90N+7&89)&(88+6(5&+12(/3.,8&*+%/:+)&(;5&.,(3)*+0+7.8+)-,+;/5/&3,.8&*+
&(8+.37./)+/&&.RS652)53&+,&*+15)&6.)+.3)&9626,9;DU851+)90N+7&89)&(88+6(5&+12
(/3.,8&*+%/:+)&(;5&.,(3*()-5,&/+,0+7.8+)-,+;/5/&3,.8&*+&(8+.37./)+/&&.R8./&*)
53&+,&*+15)&6.)+.3)&9626,9;DU/23+851+)90N+7&),+7+(:(/;)&9626,9;V)WB*.0+7.8+
-,+;/5/&89)&(88+6(5&+126()7./&(/9+)&9626,9;DX*+%/:+)&(;5&.,)*.9167.9/)+1&*+)90N+7&?
6()79))(/;5/2,()O).37./&(/9(/;&*+-,+;/5/725/65/2-.))(01++33+7&)./&*+3+&9)D
U1&*.9;*-,+;/5/72(&)+13()/.&,+;5,6+65)5/56:+,)++:+/&?&*+.9&7.8+B(11/++6&.0+
6.798+/&+6DU/2-,+;/5/72.779,,(/;(/5)90N+7&.,)90N+7&A)-5,&/+,3,.8&*+&(8+.37./)+/&
&.RS652)53&+,&*+15)&6.)+.3)&9626,9;89)&0+,+-.,&+6DU/2.779,,+/7+.3-,+;/5/7289)&
0+,+-.,&+6&.4*5,857271(7)Y,9;Z53+&2?.,6+)(;/++?-+,ZU[,+-.,&(/;&(8+1(/+)DU11
-,+;/5/7(+)B(110+3.11.B+63.,.9&7.8+?B*(7*()6+3(/+65)+1+7&(:+&+,8(/5&(./.3&*+
-,+;/5/72?8()75,,(5;+?.,6+1(:+,2.3&*+3+&9)D4,+;/5/7(+)B(&*5/.9&7.8+.31(:+0(,&*?&*+
/+B0.,/(/35/&B(110+3.11.B+69/&(1RS652).16027.8-1+&(/;B(11/++6&.0+,+-.,&+6&.
4*5,857271(7)-+,ZU[,+-.,&(/;&(8+1(/+)DU/27./;+/(&515/.8512\0(,&*6+3+7&/.&+6(/&*+
(/35/&89)&0+,+-.,&+65)5)+,(.9)56:+,)++:+/&D
]^_GF`JabHIJIKbGc
U11/+B851(;/5/&&98.,)(/7196(/;).1(6&98.,)?)O(/851(;/5/7(+)5/6*+85&.1.;(7
851(;/5/7(+)B(110+,+-.,&+63.,&*+69,5&(./.3)&962&,+5&8+/&5/669,(/;5/2-,.&.7.1Q
)-+7(3(+63.11.BQ9--+,(.6)(/7196(/;-.)&Q-,.;,+))(./3.11.BQ9-3.,.:+,511)9,:(:51D
defGFcGgfGI^chijkGKbJalI^GFGc^mdgjln
Z-+7(3(756:+,)++:+/&)?.,;,.9-).356:+,)++:+/&)?B(110+3.11.B+65)-5,&.3)&5/65,6)53+&2
8./(&.,(/;57&(:(&(+)DX*+)++:+/&)V,+;5,61+)).3)+,(.9)/+))WB(110+,+-.,&+6&.4*5,857271(7)
Y,9;Z53+&2-+,&*+ZU[,+-.,&(/;&(8+1(/+)D
`JohFpGqhFF_JHG
r5N.,*+8.,,*5;+()6+3(/+65)5/2*+8.,,*5;(7+:+/&&*5&()@,56+R.,;,+5&+,(/)+:+,(&2.,
&*5&,+)91&)(/s.3&*+3.11.B(/;t(/&,5.7915,01++6(/;759)(/;1.)).3:()(./?&*+/++63.,5
uR
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()*+),-(-*/-&0-&1+(,%)-*&123144)-&'(15+,6'41(%'0-+(%-*78-4194--2:
8-);,%'4,<'%,-(:-&;&-4-(='%,-(-*8-);,%'4,<'%,-(>
?61(%)011%,(=%8121*,(,%,-(-*0'@-&810-&&8'=17,44913';%+&12')'(161(%-*);13,'4
,(%1&1)%>
ABCDEFDEBGEHJKLMDDNEOK
P(Q,(%&'3&'(,'4810-&&8'=1'261&)1161(%:,(34+2,(=)+92+&'4810'%-0'R810-&&8'=1:1;,2+&'4
810'%-0'R810-&&8'=1:'(2,(%&'31&19&'4810-&&8'=1:-*'(Q=&'21)161&,%Q:7,44913';%+&12')
'(161(%-*);13,'4,(%1&1)%>
SMLLTBGFECGMBUKCVKKBABWKXCGOECMDEBYZNEDLEF[FHGFX
P44)1&,-+)'261&)1161(%)'(2P?\])^,(,%,'4'(2*-44-7_+;,(*-&0'%,-(`7,4491&1;-&%12-(ab
P(21&)-(\P?*-&0'(2)1(%6,'10',4-&*'c%-d8'&0'3Q34,3)b&+=\'*1%Q:-&21),=(11:7,%8,(
ef2'Q)-*%81161(%>d8'&0'3Q34,3)0'Q&15+1)%*-44-7_+;'(2-%81&'22,%,-('4,(*-&0'%,-(
*&-0%81\;-()-&](61)%,='%-&>
P44)1&,-+)'261&)1161(%)%8'%8'61(-%&1)-46129Q%811(2-*%81)%+2Q:-&%8'%8'61(-%
&1)-4612+;-(2,)3-(%,(+'%,-(-*%81)+9@13%g
);'&%,3,;'%,-(,(%81)%+2Q:0+)%91*-44-712+(%,4
'(Q-*%81*-44-7,(=-33+&)h
i k81161(%&1)-461)
i k81161(%)%'9,4,<1)
i k81161(%&1%+&()%-9')14,(1:,*'9')14,(16'4+1R)%'%+),)'6',4'941
i k81161(%3'(91'%%&,9+%12%-'=1(%)-%81&%8'(%81)%+2Q2&+=-&%-*'3%-&)+(&14'%12%-
)%+2Q3-(2+3%
i ]%913-01)+(4,l14Q%8'%'(Q'22,%,-('4,(*-&0'%,-(3'(91-9%',(12^)+9@13%-&81'4%83'&1
;&'3%,%,-(1&&1*+)'4%-;&-6,21'22,%,-('4,(*-&0'%,-(:4-)%%-*-44-7+;'*%1&210-()%&'%,-(
-*2+12,4,=1(317,%8*-44-7_+;1**-&%)`
mnApqrsAtApuvwqxyyzx{ws|zr}}xq|
mn~
}MBMCNKDE[zCTYGKX
/
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&')*+',-.+'/0.1'+23-41)5'41)6-7+)*)6./8)*)0+'-'/.084*4+&'-.32+49:;076<'=+0.=-400
>=483.*2?034*04-'/=5)*)=.50+7/)'0@ABCB?:DE9FGABCB?HH:I?BJGABCB?HH:D?BJG.*/
ABCB?HH:;?BJGABKFIE;9LBMI::HGABCB?HHHH?BJGABCB?HHHE?BJG.*/ABK?FIE;9?NAO?
H:HP&.06''*'Q.57.+'/@-'1'-'*='RK*Q'0+),.+4-S0T-4=&7-'U'-0)4*EG/.+'/FHN752I:HFPV%&'
840+=4884*+-'.+8'*+?'8'-,'*+./Q'-0''Q'*+0.041:;J3-)5I:HFW'-'/).--&'.@DIVHXPG
1.+),7'@FFV>XPG*.70'.@I;VHXPG=47,&@I:VIXPG.*/3'-)3&'-.5'/'8.@H>V;XPVY-./'F4-
&),&'-./Q'-0''Q'*+0W'-''Z3'-)'*='/62;:VEX41076<'=+0G+&'840+=4884*@[IXP41
W&)=&W'-'&'8.+454,)=)**.+7-'R*'7+-43'*).@\VEXPG+&-4864=2+43'*).@;V9XPG.*/.*'8).
@DV\XPVA*'784*).@EVEXPW.0+&'840+1-']7'*+*4*&'8.+454,)=Y-./'F4-&),&'-./Q'-0'
'Q'*+V
^'-)470./Q'-0''Q'*+0W'-''Z3'-)'*='/62D;VDX41+-'.+'/076<'=+0V%&'4*520'-)470'Q'*+0
4==7--)*,)*84-'+&.*IX41076<'=+0@'Z=57/)*,/)0'.0'3-4,-'00)4*PW'-'3*'784*).@EV\XPG
.+-).51)6-)55.+)4*@FVIXPG.*/1'6-)5'*'7+-43'*).@IV>XPV
K*.//)+)4*G/.+.)0.Q.)5.65'1-48=486)*.+)4*+&'-.32=5)*)=.50+7/)'0V_'1'-+4+&'5.+'0+Q'-0)4*
41+&'KT14-84-'/'+.)50V
`ab
defghifjhlmnopjhmjqghmpjn
J041;J3-)5I:HFGEHr;F;076<'=+0/)0=4*+)*7'/+-'.+8'*+/7'+4.*./Q'-0''Q'*+G.=-400+&'
84*4+&'-.32.*/=486)*.+)4*+&'-.32)6-7+)*)60+7/)'0@'Z=57/)*,^+7/2ABCB?HH:F?BJPs
;I076<'=+0-'=')Q)*,84*4+&'-.3234375.+)4*.*/\076<'=+0-'=')Q)*,=486)*.+)4*+&'-.32V
%&'840+1-']7'*+52-'34-+'/./Q'-0''Q'*+0+&.+5'/+4+-'.+8'*+/)0=4*+)*7.+)4*0W'-'
3*'784*).@HF076<'=+0PG-'03)-.+4-21.)57-'@D076<'=+0PG.*/=.-/).=.--'0+.*/_)=&+'-S0
^2*/-48'@F076<'=+0'.=&PV
EVIVH u'84--&.,)=vQ'*+0
%&'-'.-'-'34-+041&'84--&.,)='Q'*+0)*076<'=+0+-'.+'/W)+&)6-7+)*)6)*64+&
84*4+&'-.32.*/=486)*.+)4*=5)*)=.50+7/)'0V%&'8.<4-)+241+&'0'&'84--&.,)=
./Q'-0''Q'*+0W'-'41Y-./'H4-I)*0'Q'-)+2G)*=57/)*,8)*4-&'84--&.,)='Q'*+05)w'
=4*+70)4*G'3)0+.Z)0.*/3'+'=&).'s.*/8.<4-&'84--&.,)='Q'*+0)*=57/)*,
,.0+-4)*+'0+)*.565''/)*,G)*+-.=-.*).5&'84--&.,'.*/&'8.+7-).Vu'84--&.,)='Q'*+041
Y-./'F4-&),&'-G)*=57/)*,='*+-.5*'-Q470020+'8&'84--&.,'41.*2,-./'0'Q'-)+2G
4==7--'/)*FVDX@HEr9:;P41076<'=+0+-'.+'/)*84*4+&'-.320+7/)'0.*/)*FVHX@DrHF:P
41076<'=+0+-'.+'/)*=486)*.+)4*+&'-.320+7/)'0VJ*/*4*'W'-'-'34-+'/)*.*2&'.5+&2
Q457*+''-0+7/)'0@*xH::PV
I9
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&')*+&,)-.,'/*01*&02-0314/)*5676&/846*,2'543'942:40/'26)43'/40/'59
/*+*5;-2-)-'69402/*0/*+-)40)+'2-/4)-*0&643'<9-)-6&0/,'45=8')8'5*50*))8'6'
8'+*55843-/':'0)6='5'4))5-;&)4;,')*-;5&)-0-;>
?>@>@ B452-4/
C)5-4,1-;5-,,4)-*04024)5-4,1,&))'584:';''05'.*5)'2-0.4)-'0)6)5'4)'2=-)8-;5&)-0-;9
.45)-/&,45,D-06&;E'/)6=-)8/452-4/5-6F14/)*5694/&)'-01'/)-*0694024.5':-*&68-6)*5D
*14)5-4,1-;5-,,4)-*0>G&;E'/)6=-)848-6)*5D*1/452-4/4558D)8+-4668*&,2;'+*0-)*5'2
/,*6',D>
?>@>H I468
J-,2)*+*2'54)'5468'684:';''0*;6'5:'2=-)8-;5&)-0-;4,*0'*5-0/*+;-04)-*0=-)8
*)8'525&36>C6-03,'/46'*1G)':'06KL*806*0GD025*+'7GLG<=465'.*5)'2-04+4,'
6&;E'/)=-)8BMM)5'4)'2=-)8-;5&)-0-;N@O+3P24D>Q8'6&;E'/)=464,6*5'/'-:-03
+&,)-.,'/*0/*+-)40)+'2-/4)-*06F0*=0)*;'466*/-4)'2=-)8GLG>G&;E'/)668*&,2;'
+*0-)*5'2/,*6',D1*56-3064026D+.)*+66&33'6)-:'*1GLG>
?>@>N R)8'5J4,-3040/-'6
R)8'5+4,-3040)2-6'46'684:';''0*;6'5:'2-06&;E'/)6=8*84:';''0)5'4)'2=-)8
-;5&)-0-;9-0/,&2-036F-0/40/'569*)8'5/45/-0*+469402*)8'58'+4)*,*3-/+4,-3040/-'6>
S)-60*)/,'45=8')8'5*50*))8'6'':'0)645'4))5-;&)4;,')*-;5&)-0-;>G&;E'/)6-0)8'
/&55'0)6)&2D=-,,;'+*0-)*5'21*5*)8'5+4,-3040/-'6>
?>@>T S01'/)-*0
S00*0K5402*+-U'2/,-0-/4,)5-4,69-01'/)-*067-0/,&2-036'.6-69;4/)'5-4,9:-54,9*51&034,
VWXYZ[V\W]^`YaY\b]YacYdVW]ebfYZ[]`V[ghijklmandYopqrsqt^nWdijjuvjjkl
w542'HxH?>yz<>G*+'*1)8'6'-01'/)-*0684:';''0466*/-4)'2=-)88*6.-)4,-U4)-*0402
2'4)8>G&;E'/)668*&,2;'+*0-)*5'21*51':'5402-01'/)-*064024..5*.5-4)'40)-K
-01'/)-:')8'54.D68*&,2;'-06)-)&)'246-02-/4)'2>
{|~~~
Q*;'))'5&02'56)402)8'4/)-:-)D*1-;5&)-0-;9402)*)5D)*2')'5+-0'=8-/8.4)-'0)6+4D;'0'1-)
15*+)8-6)8'54.D9='.,4040&+;'5*1/*55',4)-:'6)&2-'6>
{|

-*+45F'564+.,'6=-,,;'6)*5'24)J%C02'56*01*50*,*03'5)840TD'456>
 >> ¡¢.,*54)-*0*1+'/840-6+6*15'6-6)40/')*¡w£I-08-;-)*56
@y
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&&()*+,-*./+*0123456*)*+7-./+&&0)8,*6579*+..6,)8)+&):&,;975);*,9(97<9,..+7-
7-)-1234*)9<,*,=*>97.+-,?+-).,+-0+:+*79@A,/+&&)&.79,B6,.*)9C0+8,=*+..6,;975
(9+79:+7(.+,.+;)8)+&):&,@D,(,-=+-<7-*0,)8)+&):+&+*>)-=B6)&+*>7;*+..6,E/,(&)-*7
(,9;795)-65:,97;.*6=+,.*7,F(&79,9,.+.*)-C,5,C0)-+.5.*71234*)9<,*,=
*0,9)(+,.@G(,C+;+C)&&>E/,/+&&(,9;795C75(9,0,-.+8,57&,C6&)9(97;+&+-<E/0+C0/+&&
+-C&6=,<,-,*+C)-)&>.+.7;*0,<,-,;79(9+5)9>)-=.,C7-=)9>56*)*+7-.)./,&&
)..6C0*,.*+-<;79)5(&+;+C)*+7-7;H1I)-=)C*+8)*+7-7;%F&@A,/+&&)&.7,8)&6)*,
5)9?,9.7;*0,,(+*0,&+)&J*7J5,.,-C0>5)&*9)-.+*+7-6.+-<+556-70+.*7C0,5+C)&.*)+-+-<
;791JC)=0,9+-)-=8+5,-*+-E+-)==+*+7-*77*0,95)9?,9.@
%-7(*+7-)&*6579*+..6,:+7(.>/+&&:,C7&&,C*,=)**0,,-=7;*9,)*5,-*;79,F(&79)*79>
:+75)9?,9)-)&>.+.;975C7-.,-*,=()*+,-*.@
K@L@M O&77=J:).,=O+75)9?,9.
379()*+,-*./07C7-.,-*,=;797(*+7-)&:&77=J:).,=:+75)9?,9.*6=+,.E:&77=/+&&:,
C7&&,C*,=).76*&+-,=:,&7/@P&).5)C>*7?+-,)-=)-<+7<,-+C;)C*79.QR%3S(97;+&+-<E
C+9C6&)*+-<;9,,(&).5)DT%)-=IC,&&.6:.,*.)-=C>*7?+-,.QIULVIUMS/+&&:,
)-)&>W,=*7,8)&6)*,;79(7*,-*+)&5)9?,9.7;C&+-+C)&:,-,;+**7*9,)*5,-*)-=57&,C6&)9
)&*,9)*+7-.X9,.(,C*+8,&>@
YZ[[\]^_`a\Yc[d_efae`gYZ[[\h[ZZaijc[klme[ia``ckn_k\oj[e_na
L@I7*)&87&65,*7:,C7&&,C*,=pqq5r
M@O&77=/+&&:,C7&&,C*,=)**0,;7&&7/+-<*+5,(7+-*.p:).,&+-,Q(9,J*9,)*5,-*E,-=7;
R>C&,ME)-=,-=7;.*6=>S
s 379R%3(97;+&+-<)-=C+9C6&)*+-<;9,,(&).5)DT%
LS R7&&,C*/07&,:&77=+-*09,,QtSFK5ru1DI%vwM1DI%x)C6*)+-,9EOD
D+)<-7.*+C.E39)-?&+-ETyEzG%S
MS P9,()9)*+7-7;mZ_`d_{
)@
r):,&*09,,Q|SM5rC9>78+)&./+*0*0,.*6=>-65:,9EC).,-65:,9E)-=
(97C,=69,=)*,E)-=C&,)9&>5)9?C9>78+)&.}(&).5)@v
:@P97C,..p(&)C,1DI%*6:,+-).*)-=)9=C&+-+C)&C,-*9+;6<,)-=.,*)*
~M4PH)*qR,&.+6.;79L5+-6*,.@
C@
hakjecnacjckdckja`[i[ZZaijc[k;*0,+-*,98)&:,*/,,-
.(,C+5,-C7&&,C*+7-)-=(97C,..+-<+.)-*+C+()*,=*7:,<9,)*,9*0)-7-,
0769E?,,(.(,C+5,-7-+C,6-*+&C,-*9+;6<+-<+.=7-,@
=@%&+B67*L@5r7;(&).5)+-*7,)C0C9>78+)&.&):,&,=/+*0*0,.*6=>)-=
C).,-65:,9.)-=(97C,=69,=)*,)-=5)9?,=}(&).5)@v
,@
P&)C,C9>78+)&.+-*7C9>7:7F/+*0)((97(9+)*,.*6=>&):,&+-<
;@
G*79,)*)5+-+565R,&.+6.6-*+&9,)=>;79.0+(5,-*79)-)&>.+.@
tS P9,()9)*+7-7;O6;;>C7)*p
		 

M
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$

&')&*+,-./++01'23,4/5678&,9:8-.-.+9-;<5=;3*+/>4&9+=;3*+/>&=<
?/64+<;/+<&-+>&=<4,+&/,53&/@4/5678&,9A*;BB546&-CD
*'E/64+99FE,&4+GHIJ-;*+8=&9-&=<&/<4,8=84&,4+=-/8B;K+&-LMNOOPEQ&-RS
T+,98;9B6/2O38=;-+9CUVWXYZ[\]V_ZX`ZWabcZW\XVde[feggVfXZeWh
4'ijklmnmjjm
lmml

	 ollmnm	jm	
p
<'P+367+?,&93&4,69+-6-.+*;BB546&-&=<@++?-.+?,&93&B6/?/64+<;/+qq
0i	mljnmjjm'
+'P+367+-.+*;BB546&-4+,,94&/+B;,,5>463*8=+&=<?,&4+8=-6-.+M3)0-6-&,
6BB6;/'4/5678&,9,&*+,+<A*;BB546&-D0mmljklmo


mjj
ijmjjm
lm'C
B'E,&4++r;&,76,;3+6B4+,,s9-6/&K+96,;-86=0PEQqtHQuv0wOF1O''
K'u-6/+*;BB546&-4/5678&,&-swOT;=-8,&=&,5x+<C
y z6/I4+,,9;*9+-9&=<45-6@8=+90I{2tI{M'
2'T6,,+4-:.6,+*,66<8=-:60M'|2OQ)96<8;3.+?&/8=-;*+9
M'q96,&-+?,&93&&=<?+/8?.+/&,*,66<36=6=;4,+&/4+,,0E}QT'*5&z846,,
?/64+998=K9-+?C
1'u-6/+-.+0;=<8,;-+<'?,&93&8=4/5678&,9&-s~OTC
R'8&*,54/56?/+7+/7+-.+E}QT6=2O<83+-.5,9;,B6|8<+0HQuv'tOB+-&,
*678=+9+/;30z}u'&=<9-6/+8=,8r;8<=8-/6K+=C
h
`YcfeZWVXZfX\ZVd
~CMC2 T6,,+4-86=6Bu?+483+=9
},66<9&3?,+9B6/?.&/3&46@8=+-849-;<8+9:8,,*+</&:=6=T54,+M><&526B-/+&-3+=-&-
B6,,6:8=K-83+s?68=-9F?/+<69+&=<&-2>M>R>&=<.?69-s<69+
~CMCM {&=<,8=K6Bu?+483+=909'
uG2|Ms3)PGGIvEuvHqQ{GEJPqI}GzvPGJT{ETv))GTIqvC
2CJ,,6:-;*+-6B8,,TvQE)GIG)>&9B&/&9-.+7&4;;3:8,,&,,6:C
M~
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&()*+,-+./-)00-1)2+-34.56786053-+)67+6296)1836++)7:/4)79-;+)7::-7+34<+)0-=&
>?@?ABCDEF&
G&H328-+,-/3661=2053-=670-3+)7:)8-.7+)38-7+;)I.:2+)67
J&H328-+,-=2053-)72;-I;):-;2+-18-7+;)I.:-KLMJNOP&
QRSTUWXYZZY[Y\\]^_`\Y]^Ya^bcY^]dYe[YZd^ba`cYf`[gYdbZ[]\Y\hXY^Y]^Ya^bcY^]dYe
[YZd^ba`cYb\Zid]j]bk]fkYlm]bZd]bZ[ikedYnoY^]d`^Ye`^bZcdXYok]\n]o^Yo]^]dbiZ
o^i[Y\\l
<&O-7+;)I.:-+./-p)+,)7qL0)7.+-=6I8633-8+)672+JNOI6;r<0)7.+-=2+%<LL;50&
q&A;27=I-;532=02p)+,5)5-++--s.2334)7+6+p6%M0t8;469)23=K255;6*)02+-34L&<0t6I
532=02)7-28,+./-P&
u&F7+-;+,-B./v-8+w>7.0/-;67+,-=2053-32/-3=&
x&B+6;-532=02=2053-=)72I;--y-;2+MxLNO6;/-36pzp)+,)7255;6*)02+-34qL0)7.+-=6I
/36618633-8+)67&
{&B,)5=2053-=|}R~TQ)7/2+8,-=K2I+-;8633-8+)67I;60-28,=./v-8+)=86053-+-1P+6
|^iZd]cY]fi^]di^bY\Z[&
@?AFF9-;4-II6;+=,6.31/-021-+68633-8++,-I.33%0t/3661=2053-2+-28,+)0-56)7+&w7
+,--9-7++,2+3-==+,27r0t6I/3661)=8633-8+-1z+,-=2053-p)33/-5;68-==-12=1-=8;)/-1
2/69--*8-5++,2++,-532=02p)3376+/-1)9)1-1)7+6+p6+./-=&D331-9)2+)67=p)33/-;-86;1-1
67+,-HEp6;=,--+&A,)==)7:3-532=02=2053-=,6.31/-I;6y-7z=+6;-1271=,)55-1p)+,+,-
5;)02;4=-+6I=2053-=&
x&%&G B,)55)7:6IB5-8)0-7K=P
TmTQdifYf]d[X\XbooYe|}R~TQ]adY^[ikkY[dbiZa^inY][X\`fY[dlkY]\Y
bZ[k`eYU

?7-5;)02;4=-+6I=2053-=I6;-28,=./v-8+

?7-/28M.5=-+6I=2053-=I6;-28,=./v-8+K.73-==6734=)7:3-=2053-292)32/3-P
B2053-==,6.31/-=,)55-1671;4)8-miZe]_dX^i`cXSX`^\e]_6734&
D=0.8,2=56==)/3-z286053-+-=-+6Io^bn]^_=2053-=K233+)0-56)7+=PI6;2=./v-8+=,6.31/-
/2+8,-1271=,)55-1+6:-+,-;)7+,-=20-=,)50-7+&
B,)5+,-/28M.5=-+2I+-;+,-867I);02+)676I;-8-)5+6I+,-5;)02;4=-+/4;67+2:-
t2/6;2+6;)-=zw78&
>6@?A=,)5/28M.523)s.6+=6I=2053-=)7+,-=20-=,)50-7+2=+,-5;)02;4=2053-=I;60+,-
=20-=./v-8+&
O67+28+F>F8.=+60-;=-;9)8-+61-+-;0)7-+,-32+-=+5)8.5+)0-I6;46.;=)+-271+,-
=8,-1.3)7:1-213)7-&-86;1+,-F>FA;28)7:7.0/-;I;60+,-+656I-28,2);/)33I6;46.;
;-86;1=271+;28)7:5.;56=-=&
%{
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
&'()*+,-.//.01&'(.2.34(.'02456-'789:)6)09/;.';('6-.//.01<
=8)3(;'0.3/43>41.0168./?76(:)6)0(('048))?@2;'0(41)84:<3'?409
?-'01@2;'0(41)84:<3'?
,ABCCB&D+EEF=,,
&4:))84+8))?
,4?/8)G'';9.04(';
H;'0(41)I4:';4(';.)6JB03<
KLLC)006M8N40.4E;.N)
=5('0JC+OPQRO
C*RSRTQRSTRKPL
H*UOLTVQVTLOLO
WXZ[\]^`abcd]\adZef]cegdf]ea
WXh
ijklmnopcljqojr
s;.(()0.02';?)93'06)0(t.88:)1.N)0:M)43-/4(.)0(/;.';('709);1'.01/;'('3'86/)3.2.3
)N4874(.'06409/;.';(';)3).N.01(;)4(?)0(<
WXu
vopwxyz{wqrlm|yjp`}|qwxyzd~yn
+3'?/8)()?)9.348-.6(';M409/-M6.348)54?.03879.01N.(486.106J-).1-(J409t).1-(6-'789
:)':(4.0)9t.(-.0VS94M6/;.';('.0.(.4(.'0'2(-);4/M'06(79M<=GD/);2';?403)6(4(76
6-'789:);)3';9)94((-.6N.6.(<
WX
czwjwxyzgylmyrlm|[oqrq
8''9:46)938.0.34884:';4(';M()6(6t.88:)':(4.0)9t.(-.0VS94M6/;.';('(-)6(4;('2/;'('3'8
(-);4/M409(-)0)N);MVS94M6TK94M6<-)6)()6(6t.88.03879)*
A)?4('8'1M/;'2.8)*3'?/8)():8''93'70(t.(-9.22);)0(.48409/84()8)(3'70(
G-)?.6(;M/;'2.8)*&J3;)4(.0.0)J6'9.7?J/'(466.7?J34;:'09.'5.9)J?410)6.7?J
('(48:.8.;7:.0J48>48.0)/-'6/-4(46)J46/4;(4()4?.0'(;4062);46)J4840.0)
4?.0'(;4062);46)
C;)10403M()6(*,);7?';7;.0)/;)10403M()6(t.88:)':(4.0)94(:46)8.0)t.(-.0K
94M6/;.';('(;)4(?)0(.0488t'?)0'23-.89T:)4;.01/'()0(.484(:46)8.0)409414.0.2
38.0.3488M.09.34()9<
WX
[nlmwlq|
B24/4(.)0(9')60'(-4N)6722.3.)0((.667)2;'?4:.'/6M/);2';?)942();/;'1;)66.'0'0=DHFT
(4;1)()9BJ4:.'/6Mt.88:)/);2';?)9<-).0N)6(.14(';t.889)();?.0)(-)642)6(?)(-'92';
':(4.0.01(.667)Jt-.3-3'789.03879)GT17.9)93';)0))98):.'/6M<
QL
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'
)*+,-./*01,24556557689
;<=>?@>ABCD?EA?@FGCD?@>=HIJKBLEFLEAB=@DJBLEMABCD?EA=AFG?@?F=GGN?@D?F=BEDO?GGPE
QEMKJM<EDO?BL?@RSD=NAQM?JMBJBLE?@?B?=B?J@JKABCDNBME=B<E@B=@DETEMNSOEEUAVWXYZD=NA[
OL?GEJ@BLEM=QN\
%&]
^9_+`a*b68+*/
)6c_,/6+d/-26+_/65
e*56b,86
f_/,8.g/6*97689 h8+-ig/6*97689j
k-8.g6/7
l-bb-mno0
I?<?@>
p?BL?@RSD=NA
QM?JMBJBME=B<E@B
?@?B?=B?J@C@GEAA
JBLEMO?AEAQEF?K?ED
qTEMNrOEEUAstZ
D=NAsC@GEAA
JBLEMO?AEAQEF?K?ED
p?BL?@uvD=NA=KBEM
BLEG=ABDJAEJKABCDN
<ED?F=B?J@C@GEAA
JBLEMO?AEAQEF?K?ED

IME=B<E@Bw?ABJMN
x



yED?F=Gw?ABJMN
x



zE<J>M=QL?FA
x



{LNA?F=Gq|=<
x
x
x

}?B=G~?>@A
x
x
x

wE?>LB
x



pE?>LB
x
x
x

qH{~
x



~N<QBJ<AIJ|?F?B?EA
x
x
@=@J@>J?@>P=A?A
BLMJC>LJCBABCDN
x

HJ@FJ<?B=@B
yED?F=B?J@A
x
x
@=@J@>J?@>P=A?A
BLMJC>LJCBABCDN
x

wE<=BJGJ>N{MJK?GE
x
x
x

HLE<?ABMN{MJK?GE
x
x
x

{ME>@=@FNIEABVAEMC<
JMCM?@E[
JM=GGOJ<E@JKFL?GD
PE=M?@>QJBE@B?=G
x

p?BL?@ZD=NA
QM?JMBJBME=B<E@B
;KXOLE@FG?@?F=GGN
?@D?F=BED
;KXOLE@FG?@?F=GGN
?@D?F=BED

=D?JGJ>NIC<JM
yE=ACME<E@BA
x

x
qTEMNSOEEUAstZ
D=NA


}EM?K?F=B?J@JKI?AACE
T=?G=P?G?BN
x




MEAL?JQAN
x

x

{L=M<=FJU?@EB?FABCD?EA




GJJDYP=AEDP?J<=MUEMA
VJQB?J@=G[
x
x=
x

;PMCB?@?PHJ<QG?=@FE

x
BE=FLFG?@?FT?A?B


~CPAECE@B@B?F=@FEM
ILEM=QN



x
~CMT?T=G~B=BCA



x
I?AACEKMJ<=P?JQANJMACM>?F=GQMJFEDCMEKJGGJO?@>QMJ>MEAA?J@J@=@qB=M>EBEDBNMJA?@E
U?@=AE?@L?P?BJMKJMq<CB=@BAJMKJGGJO?@><JABMEFE@BG?@EJKANABE<?FBLEM=QNKJMwqR
<CB=@BA<CABPE=T=?G=PGEQM?JMBJBLEAB=MBJKBLEM=QN\
u
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%%&')*+,--./*0+1,)/2'*33*4,)567*57/--,*)*)1)89:;<=&'*789:;>.+1)+-*7>*-+7/?/)+
-@-+/>,?+A/716@'*7B8;C>.+1)+-,-1D1,3103/E10,*6-@4,330/6/7'*7>/21'+/7-,5),)5
,)'*7>/2?*)-/)+0.+67,*7+*+7/1+>/)+,),+,1+,*)F
%%%G6+,*)130,*6-@H4,+A,)IJ21@-*'31-+2*-/*',07.+,),0
%%%%K*)5+/7>'*33*4L.64,33*??.7/D/7@M>*)+A-0@>/2,?13N?3,),?1321+17/D,/4*76A*)/
?*)+1?+F
OP31->1-1>63/-'*7P=/D13.1+,*)1+-+/12@L-+1+/*)Q1@RES@?3/CT67/2*-/ERECEUE1)2MA
6*-+L2*-/
1SV:67*',3,)51)2?,7?.31+,)5'7//631->1QWV-1>63/-4,330/?*33/?+/21++A//)2*'S@?3/CF
<BRN<BC-1>63/-4,330/?*33/?+/2/D/7@U4//X-'*7+A/',7-+I>*)+A-E+A/)/D/7@RC4//X-
.)+,3+A//)2*'+7/1+>/)+F
YZ[]^_`ab^]^cdfg^gg^hd
YZ[Y _ijkjlmno^ppqrjs`ntkudlmnov
:*7+A/6.76*-/-*'+A,--+.2@E61+,/)+--A*.320/7/L/D13.1+/2'*77/-6*)-//D/7@w4//X-xNLy
21@-F&)122,+,*)+*101-/3,)/-?1)E?*)',7>1+*7@-?1)--A*.3213-*0/*0+1,)/2)*+3/--+A1)U
4//X-'*33*4,)5,),+,132*?.>/)+1+,*)*'*0z/?+,D/7/-6*)-/F
;/-6*)-/1)267*57/--,*)4,330//D13.1+/2,)+A,--+.2@.-,)5+A/)/4,)+/7)1+,*)13?7,+/7,1
67*6*-/20@+A/7/D,-/2;/-6*)-/8D13.1+,*)S7,+/7,1,){*3,2<.>*7-|;8S&{<}5.,2/3,)/
|D/7-,*)RFR}F
CJSA1)5/-,)+A/3175/-+2,1>/+/7|.),2,>/)-,*)13>/1-.7/>/)+}*'+A/+.>*7
3/-,*)-1)2+A/-A*7+/-+2,1>/+/7,)+A/?1-/*'>13,5)1)+3@>6A)*2/-17/.-/2,)+A/;8S&{<
?7,+/7,1F
RJFRFRQ/',),+,*)-
8D13.103/'*7+*,?,+@FV3361+,/)+-4,330//D13.103/'*7+*,?,+@'7*>+A/+,>/*'+A/,7
',7-++7/1+>/)+4,+A,07.+,),0F
8D13.103/'*7*0z/?+,D/7/-6*)-/FG)3@+A*-/61+,/)+-4A*A1D/>/1-.7103/2,-/1-/
67/-/)+1+01-/3,)/EA1D/7/?/,D/21+3/1-+*)/?@?3/*'+A/716@E1)2A1D/A12+A/,72,-/1-/
7/L/D13.1+/24,330/?*)-,2/7/2/D13.103/'*77/-6*)-/F<A/-/61+,/)+-4,33A1D/+A/,7
7/-6*)-/?31--,',/21??*72,)5+*+A/2/',),+,*)--+1+/20/3*4F|W*+/TP1+,/)+-4A*/A,0,+
*0z/?+,D/2,-/1-/67*57/--,*)67,*7+*+A//)2*'?@?3/R4,3313-*0/?*)-,2/7/2
/D13.103/F}
8D13.103/W*)L<175/+Q,-/1-/;/-6*)-/FP1+,/)+-4A*A1D/3/-,*)-67/-/)+1+01-/3,)/
+A1+17//D13.103/0.+2*)*+>//++A/2/',),+,*)-*'>/1-.7103/2,-/1-/EA1D/7/?/,D/21+
3/1-+*)/?@?3/*'+A/716@E1)2A1D/A12+A/,72,-/1-/7/L/D13.1+/24,330/?*)-,2/7/2
/D13.103/'*7)*)L+175/+2,-/1-/F<A/7/-6*)-/1--/-->/)+,-01-/2*)+A/67/-/)?/E
10-/)?/E*7.)/.,D*?1367*57/--,*)*'+A/3/-,*)-F
RJFRFCQ,-/1-/P171>/+/7-
/1-.7103/2,-/1-/F/1-.7103/3/-,*)-17/2/',)/21-+A*-/+A1+?1)0/1??.71+/3@
IC
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()*&+-.'/0&'(/1.&+-%&.(-1.201.3&(/+-'%&/&*/14&*&51*+&+6'(789%%4:5;&(/
<=*':1*'(7>9%%?-/;@A(5'.BCDEB1*5'0-F&*(4:50-.-5'0&<'%GH00/)%1*
%&'()*&%&./(%)(/4&*&51*+&+-.%-00-%&/&*(21*+&5-%'0I*'5/-1.(1I5&./-%&/&*(6G
J1/&KA)%1*0&(-1.(/;'/'*&(-/)'/&+-.'F*&L-1)(0:-**'+-'/&+'*&'5'.4&51.(-+&*&+
%&'()*'40&-I/;&*&;'(4&&.+15)%&./&+F*13*&((-1.-./;&(&0&(-1.(I1001?-.3/;&
51%F0&/-1.1I*'+-'/-1.G
C'0-3.'./0:%F;.1+&(GA14&51.(-+&*&+F'/;1013-5'00:&.0'*3&+'.+%&'()*'40&B'
0:%F;.1+&%)(/4&7>M%%-.(;1*/'<-(?;&.'((&((&+4:@A(5'.2@A(5'.(0-5&
/;-5N.&((*&51%%&.+&+/14&.13*&'/&*/;'.M%%6GH/4'(&0-.&'.+-.I1001?=)FB1.0:
/;&(;1*/'<-(?-004&%&'()*&+'.+I1001?&+G
J1.=%&'()*'40&+-(&'(&GH001/;&*0&(-1.(21*(-/&(1I+-(&'(&6B-.50)+-.3(%'000&(-1.(
201.3&(/+-'%&/&*O>9%%1*F'/;1013-5'00:%F;.1+&(?-/;7>9/1O>M%%(;1*/'<-(6B
'*&51.(-+&*&+.1.=%&'()*'40&+-(&'(&GP1.&0&(-1.(B0&F/1%&.-.3&'0+-(&'(&B'(5-/&(B
F0&)*'0QF&*-5'*+-'0&II)(-1.(B0:%F;'.3-/-(5)/-(QF)0%1.-/-(B-.I0'%%'/1*:4*&'(/+-(&'(&B
'.+'4+1%-.'0%'((&(2.1/I1001?&+4:@A1*CDE6B'*&51.(-+&*&+'(.1.=%&'()*'40&G
J1/&K@:(/-50&(-1.(/;'/%&&//;&5*-/&*-'I1**'+-13*'F;-5'00:+&I-.&+(-%F0&5:(/(
(;1)0+.1/4&51.(-+&*&+'(%'0-3.'./0&(-1.(2.&-/;&*%&'()*'40&.1*.1.=%&'()*'40&6
(-.5&/;&:'*&B4:+&I-.-/-1.B(-%F0&5:(/(G
R@:(/-50&(-1.(S/;1)3;//1*&F*&(&./5:(/-5%&/'(/'(&(5'.4&51.(-+&*&+'(%&'()*'40&
0&(-1.(B-I/;&:%&&//;&+&I-.-/-1.1I%&'()*'4-0-/:+&(5*-4&+'41L&GT1?&L&*B-I.1.=
5:(/-50&(-1.('*&F*&(&./-./;&('%&F'/-&./B/;&(&'*&F*&I&**&+I1*(&0&5/-1.'(/'*3&/
0&(-1.(G
A'*3&/0&(-1.(GH00%&'()*'40&0&(-1.()F/1'%'<-%)%1I80&(-1.(F&*1*3'.'.+M
0&(-1.(-./1/'0B*&F*&(&./'/-L&1I'00-.L10L&+1*3'.(B(;1)0+4&-+&./-I-&+'(UVWXYU
[Y\]^_\'.+*&51*+&+'.+%&'()*&+'/4'(&0-.&GA'*3&/0&(-1.((;1)0+4&(&0&5/&+1./;&
4'(-(1I/;&-*(-`&20&(-1.(?-/;/;&01.3&(/+-'%&/&*6B4&*&F*&(&./'/-L&1I'00-.L10L&+
1*3'.(B4)/-.'++-/-1.(;1)0+4&/;1(&/;'/0&.+/;&%(&0L&(/1*&F*1+)5-40&*&F&'/&+
%&'()*&%&./(GE/%':4&/;&5'(&/;'/B1.155'(-1.B/;&0'*3&(/0&(-1.+1&(.1/0&.+-/(&0I
/1*&F*1+)5-40&%&'()*&%&./-.?;-5;5-*5)%(/'.5&/;&.&</0'*3&(/0&(-1.?;-5;5'.4&
%&'()*&+*&F*1+)5-40:(;1)0+4&(&0&5/&+GH()%1I/;&+-'%&/&*(201.3&(/I1*.1.=
.1+'00&(-1.(B(;1*/'<-(I1*.1+'00&(-1.(6I1*'00/'*3&/0&(-1.(?-004&5'05)0'/&+'.+
*&F1*/&+'(/;&4'(&0-.&()%+-'%&/&*(GEI0:%F;.1+&('*&/14&-.50)+&+-./;&()%B
/;&.1.0:/;&(;1*/'<-(-('++&+-./1/;&()%GA;&4'(&0-.&()%+-'%&/&*(?-004&)(&+
'(*&I&*&.5&/1I)*/;&*5;'*'5/&*-`&'.:14a&5/-L&/)%1**&3*&((-1.-./;&%&'()*'40&
+-%&.(-1.1I/;&+-(&'(&G
J1.=/'*3&/0&(-1.(GH001/;&*0&(-1.(21*(-/&(1I+-(&'(&6-.50)+-.3'.:%&'()*'40&
0&(-1.(1L&*'.+'41L&/;&M/'*3&/0&(-1.((;1)0+4&-+&./-I-&+'(_^_bUVWXYU[Y\]^_\'.+
(;1)0+'0(14&*&51*+&+'/4'(&0-.&GC&'()*&%&./(1I/;&(&0&(-1.('*&.1/*&c)-*&+B4)/
/;&F*&(&.5&B'4(&.5&B1*-.*'*&5'(&().&c)-L15'0F*13*&((-1.1I&'5;(;1)0+4&.1/&+
dd
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()*&()%,(--(./)01
23121467%&(89,(':;<-)<%=(>(,67<9)'<?-7@=97<97
A--B7<9)'7B7>%99&()-8?7%<C7><>8'7D('878=>B7%'=D>(%<%=(>1A--?<97-=>7
7;<-)<%=(>99&()-8?707',('B78<9D-(97-E<90(99=?-7%(%&7?7*=>>=>*(,%'7<%B7>%<>8
>7;7'B('7%&<>FG8<E9?7,('7%&7?7*=>>=>*(,%&7%'7<%B7>%1H>%&=99%)8EI.70'7,7'
D(>%'<9%/7>&<>D78JK9D<>9,('=B<*=>*(,%&7D&79%I<?8(B7>I<>807-;=9I<>86LH,('
=B<*=>*(,%&7?'<=>I%&()*&(%&7'%7D&>=M)79D<>?7)978=,%&7'7=9<0'799=>*'7<9(>1
K&79<B7B7%&(8(,<99799B7>%<>8%&79<B7%7D&>=M)79&()-8?7)978%(D&<'<D%7'=N7
7<D&=87>%=,=78<>8'70('%78-79=(><%?<97-=>7<>88)'=>*,(--(./)01HB<*=>*/?<978
7;<-)<%=(>=90'7,7''78%(7;<-)<%=(>?ED-=>=D<-7O<B=><%=(>)>-799%&7-79=(>P9Q?7=>*
,(--(.78D<>>(%?7=B<*78?)%<'7<99799<?-7?ED-=>=D<-7O<B1
J-=>=D<--79=(>9J-=>=D<--79=(>9.=--(>-E?7D(>9=87'78B7<9)'<?-7.&7>%&7E<'7
9)07',=D=<-PSSI9C=>>(8)-79<>80<-0<?-7-EB0&>(879Q<>8T23BB8=<B7%7'<9
<9979978)9=>*D<-=07'9PSSI9C=>>(8)-79Q1H>%&7D<97(,9C=>-79=(>9I8(D)B7>%<%=(>?E
D(-('0&(%(*'<0&EI=>D-)8=>*<')-7'%(79%=B<%7%&79=N7(,%&7-79=(>I=9'7D(BB7>8781
J&79%O/'<EU79=(>9(>D&79%O/'<E<'7<DD70%<?-7<9B7<9)'<?-7-79=(>9.&7>%&7E<'7
D-7<'-E87,=>78<>89)''()>878?E<7'<%78-)>*1V(.7;7'IJK=90'7,7'<?-71
J(>;7>%=(><-JK<>86LHK&=9*)=87-=>7&<987,=>78B7<9)'<?=-=%E(,-79=(>9(>JK
9D<>?<978(>%&7<99)B0%=(>%&<%JK9-=D7%&=DC>799=9WBB('-7991H,JK9D<>9&<;7
9-=D7%&=DC>799*'7<%7'%&<>WBBI%&7B=>=B)B9=N7,('<B7<9)'<?-7-79=(>9&()-8?7
%.=D7%&79-=D7%&=DC>79916LH=9<-9(<DD70%<?-7=>D7'%<=>9=%)<%=(>9PSS,('?(8E
9D<>9Q1
X97(,6LH'7B<=>9<D(B0-7O=99)716LH&<97OD7--7>%D(>%'<9%I90<%=<-I<>8%7B0('<-
'79(-)%=(>Y&(.7;7'I%&7'7<'7B<>E=B<*7<DM)=9=%=(>;<'=<?-79=>;(-;78=>6LHI.&=D&
*'7<%-E=B0<D%=B<*7M)<-=%EI-79=(>D(>90=D)=%EI<>8B7<9)'7B7>%1Z)'%&7'B('7I%&7
<;<=-<?=-=%E(,6LH=9;<'=<?-7*-(?<--E1A9.=%&JKI=,<>6LH=907',('B78I%&7
%7D&>=D<-907D=,=D<%=(>9(,%&79D<>>=>*97M)7>D79)9789&()-8?7(0%=B=N78,('%&7
7;<-)<%=(>(,%&7%E07<>89=%7(,8=97<971Z)'%&7'B('7I<9.=%&JKI%&7B(8<-=%E)978<%
,(--(./)09&()-8?7%&79<B7<9.<9)978<%?<97-=>7<>8%&7-79=(>99&()-8?7
B7<9)'78[<9979978(>%&79<B70)-9797M)7>D71H%=9?7E(>8%&79D(07(,%&7L:JH\K
*)=87-=>79%(0'79D'=?7907D=,=D6LH0)-9797M)7>D70<'<B7%7'9,('<--9D<>>7'9I?(8E
0<'%9I<>88=97<9791H87<--EI%&79<B7%E07(,9D<>>7'9&()-8?7)978<>8%&7=B<*7
<DM)=9=%=(>0'(%(D(-9&()-8?7,(--(.78<9D-(97-E<90(99=?-7%(0'=('9D<>91](8E9D<>9
9&()-8?707',('B78.=%&?'7<%&/&(-89D<>>=>*%7D&>=M)79I=,0(99=?-71
^:K/JKA%0'797>%I%&7-(.8(97('<%%7>)<%=(>D(''7D%=(>JK0('%=(>(,<D(B?=>78
^:K/JK=9>(%<-.<E9(,(0%=B<-8=<*>(9%=DJKM)<-=%E,(')97.=%&L:JH\K
B7<9)'7B7>%91V(.7;7'I=,%&7JK07',('B78<90<'%(,<^:K/JK=9(,=87>%=D<-
8=<*>(9%=DM)<-=%E%(<8=<*>(9%=DJKP.=%&H_<>8('<-D(>%'<9%Q=>%&7(0=>=(>(,%&7
4`
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&''()&*(+,-.0,(.-&1+,%*(0,&'&.,1+2+34-+34567&*+,&-&8+349:6;56%(-)4<1408&*
=:5>?6@4(1<*4@4-+1(-0%(-)4<140,-+4*%3(-.4()'AB,+3%&-C4-+,&-('56,-
(%%<*(+4'A@4(1<*,-.%(-%4*'41,&-1&C4*+,@4DE&+423&B4C4*2+3(++349:67&*+,&-&8
+3456,-+*&0<%41(00,+,&-('0(+(B3,%3@(A),(1(-,-C41+,.(+&*,8,+,1-&+*&<+,-4'A&*
14*,(''A74*8&*@40D
F'+*(1&<-0F'+*(1&<-0,1-&+<148<',-(11411@4-+&8'41,&-1,G4(-013&<'0-&+)4<140
(1(@4+3&0&8@4(1<*4@4-+DF'+*(1&<-04H(@,-(+,&-1%(--&+)4*47*&0<%40,-+34,*
4-+,*4+A8&*,-0474-04-+*4C,4B(+('(+4*0(+4(-02)4%(<14+34A(*4&74*(+&*0474-04-+2,+
%(--&+)4.<(*(-+440+3(++341(@4+4%3-,I<4(-0@4(1<*4@4-+1B,'')4+(J4-8*&@&-4
(11411@4-++&+34-4H+D>8-4B'41,&-1(*4,04-+,8,40)A<'+*(1&<-0,-+34%&<*14&8+34
1+<0A2%&-8,*@(+,&-)A56&*K=>,1(0C,140D>8+34*4,1%&-%4*-()&<+*(0,(+,&-
4H7&1<*4(+562K=>@(A)4<140,-1+4(0&856,-14'4%+40,-1+(-%41D
:-0&1%&7A2L(7(*&1%&7A634<+,',G(+,&-&8+3414+4%3-,I<418&*&)M4%+,C4+<@&*
4C('<(+,&-,1-&+(0C,140DN&B4C4*21<%3+4%3-,I<41@(A)4<148<'+&%&-8,*@%&@7'4+4
7(+3&'&.,%('*417&-14B34-),&71,41(*4&)+(,-40&*+&04+4*@,-4*4'(714,-+*,('1B34*4
*4%<**4-%48&''&B,-.%&@7'4+4*417&-14O5=P&*1<*.,%('*414%+,&-,1(-4-07&,-+D
6<@&*@(*J4*16<@&*@(*J4*1B,''-&+)4<140+&(11411*417&-14D
5A+&'&.A2N,1+&'&.A63414+4%3-,I<41%(-)4<140+&0,884*4-+,(+4)4+B44-7(*+,('
*417&-141O9=P(-0%&@7'4+4*417&-141O5=P,-*(*4%(141OQQ2*41,0<(''41,&-1,-+<@&*
+A74121<%3(1.4*@%4''+<@&*12B34*4J-&B-*41,0<(')4-,.-+<@&*1%(-*4@(,-PD
634%A+&'&.,%('%&-8,*@(+,&-&8+34-4&7'(1+,%&*,.,-&8(-A488<1,&-+3(+(774(*1&*
B&*14-10<*,-.+*4(+@4-+B34-+34@4(1<*()'4+<@&*3(1@4+%*,+4*,(8&**417&-14&*
1+()'40,14(14,1@(-0(+&*A+&0,884*4-+,(+4)4+B44-*417&-14&*1+()'40,14(14O(-
488<1,&-@(A)4(1,044884%+&8+34+*4(+@4-+P(-07*&.*411,C40,14(14D
RST;9:6U3,'4RST;9:6*417&-14(11411@4-+1-440(00,+,&-('1+<0A2,+,11&@4+,@41
*4(1&-()'4+&,-%&*7&*(+4+34<14&8RST;9:61%(--,-.+&%&@7'4@4-+561%(--,-.,-
(11411@4-+&87*&.*411,&-O7(*+,%<'(*'A7&11,)'4V
-4BV
0,14(14PDE4B'41,&-1&-+34)(1,1
&8RST;9:6,@(.,-.%(-)4,04-+,8,40(%%&*0,-.+&+348&''&B,-.('.&*,+3@W
(DE4.(+,C4RST;9:6(+)(14',-42B,+3(7&1,+,C4RST;9:6(+8&''&B;<7,1(1,.-&8
9S)(140&-(-4B'41,&-D
)DE&RST;9:6(+)(14',-4(-0(7&1,+,C4RST;9:6(+8&''&B;<7W>8+347&1,+,C4RST;
9:6(+8&''&B;<7%&**417&-01+&(-4B1,+4&80,14(14%&-8,*@40)A562+3,1,19SD>8
+347&1,+,C4RST;9:6(+8&''&B;<7,1-&+%&-8,*@40(1(-4B1,+4&80,14(14&-562
(00,+,&-('8&''&B;<7561%(-1(*4-44040+&04+4*@,-4,8+34*4,1+*<'A7*&.*411,&-
&%%<**,-.(++3(+1,+4O,81&2+340(+4&89SB,'')4+340(+4&8+34,-,+,('()-&*@('
RST;9:61%(-PD>8+347&1,+,C4RST;9:6(+8&''&B;<7%&**417&-01+&(7*4;4H,1+,-.
1,+4&80,14(14&-56+3(+,1-&+7*&.*411,-.&-+34)(1,1&8+34(-(+&@,%,@(.412+3,1
,1-&+9SD
%DRST;9:6@(A)4<140+&<7.*(04(*417&-14+&(5=,-(@(--4*1,@,'(*+&(),&71A
,-%(141B34*4(*41,0<('*(0,&.*(73,%()-&*@(',+A,1+3&<.3++&*47*414-+8,)*&1,1&*
YZ
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'(()*+,./01%023456789.)*:/)%&)(&1;%:'*&0%/21<=>0?(2%?0&:)@0<A
=0%&()>0=)*:/0?(2:2&2<'*=%1??2(:0=>A=)%0'%07%?0&)3)&;0=)&'<<):0(':1(032(:/0
)*=)&':)2*,B2C0@0(D):;1%:>0'&E*2C<0=+0=:/':>2:/'??(2'&/0%;'A<0'=:23'<%0
?2%):)@0FG=10:2<);):':)2*%23456789.'*=>)2?%A(0%2<1:)2*H%0*%):)@):A,
I2:0JKL?2%):)@0M456789.%&'*<0%)2*;0'*%2*0C/)&/)%456'@)=C):/'*1?:'E0
+(0':0(:/'*:C)&0:/':23:/0%1((21*=)*+:)%%102*:/0'::0*1':)2*&2((0&:0=);'+0,
NO,N,PG0%?2*%0F():0()'
NO,N,P,N 9@'<1':)2*23.'(+0:S0%)2*%
F2;?<0:0G0%?2*%0TFGUJ5)%'??0'('*&023'<<:'(+0:<0%)2*%,K*A?':/2<2+)&'<
<A;?/*2=0%TC/0:/0(:'(+0:2(*2*7:'(+0:U;1%:/'@0(0=1&:)2*)*%/2(:'V)%:2WNO
;;,

8'(:)'<G0%?2*%0T8GUJK:<0'%:'XOY=0&(0'%0)*:/0%1;23:/0=)';0:0(%23:'(+0:
<0%)2*%D:'E)*+'%(030(0*&0:/0>'%0<)*0%1;=)';0:0(%,

8(2+(0%%)@05)%0'%0T85UJK:<0'%:'ZOY)*&(0'%0)*:/0%1;23:/0=)';0:0(%23
:'(+0:<0%)2*%D:'E)*+'%(030(0*&0:/0%;'<<0%:%1;2*%:1=AT:/)%)*&<1=0%:/0
>'%0<)*0%1;)3:/':)%:/0%;'<<0%:2*%:1=AU,[*'==):)2*:2:/0(0<':)@0)*&(0'%023
ZOYD:/0%1;;1%:'<%2=0;2*%:(':0'*'>%2<1:0)*&(0'%023':<0'%:\;;,TI2:0J
:/0'??0'('*&0232*02(;2(0*0C<0%)2*%)%'<%2&2*%)=0(0=?(2+(0%%)2*%U,

]:'><05)%0'%0T]5UJI0):/0(%133)&)0*:%/()*E'+0:2^1'<)3A32(8G*2(%133)&)0*:
)*&(0'%0:2^1'<)3A32(85D:'E)*+'%(030(0*&0:/0%;'<<0%:%1;=)';0:0(%C/)<02*
%:1=A,

NO,N,P,Z 9@'<1':)2*23I2*7.'(+0:S0%)2*%

F2;?<0:0G0%?2*%0TFGUJ5)%'??0'('*&023'<<*2*7:'(+0:<0%)2*%'*=*2(;'<)_':)2*
23:1;2(;'(E0(<0@0<,K<<<A;?/*2=0%;1%:>0*2*7?':/2<2+)&'<)*%)_0TWNO;;
%/2(:'V)%U,

I2:0J[3:1;2(;'(E0(%'(0)*):)'<<A'>2@0:/01??0(*2(;'<<);):D:/0A;1%:
*2(;'<)_032('?':)0*::2>0&2*%)=0(0=)*&2;?<0:0&<)*)&'<(0%?2*%0,

I2*7FGHI2*785J80(%)%:0*&0232*02(;2(0*2*7:'(+0:<0%)2*T%U'*=H2(
;')*:0*'*&023:1;2(;'(E0(<0@0<'>2@0:/0*2(;'<<);):%,

8(2+(0%%)@05)%0'%0T85UJK??0'('*&0232*02(;2(0*0C<0%)2*%'*=H2(
	`	abcd230V)%:)*+*2*7:'(+0:<0%)2*%,e`	abcd
%/21<=*2:*2(;'<<A:(1;?:'(+0:<0%)2*%:':1%,[:;1%:>0(0?(0%0*:':)@0232@0('<<
=)%0'%0%:':1%&/'*+0D*2:'%)*+<0<0%)2*)*&(0'%0,
Xf
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'()*+(-.&/-010)+0/223)4)564)47'-0+/'8&/23)42)4&932/:./1'3)4-&;'(/)1343)4
)5'(/'0/-'34+1(923.3-42()*&<10/=-3&342*.(.30.*>2'-4./2;-4<'(/10)+0/223)4
2'-'*22()*&<?/.)4530>/<-'-&-'/0'3>/?9'(/@034.31-&A4=/2'3+-')0B
CDBCBEBF H=-&*-'3)4)5I/2'J=/0-&&K/21)42/

L(/?/2')=/0-&&0/21)42/32'(/?/2'0/21)42/0/.)0</<50)>'(/2'-0')5'(/'0/-'>/4'
*4'3&<32/-2/10)+0/223)4M0/.*00/4./N'-O34+-20/5/0/4./5)010)+0/223=/<32/-2/'(/
2>-&&/2'>/-2*0/>/4'20/.)0</<234./'(/'0/-'>/4'2'-0'/<PBL(/1-'3/4'Q
2?/2'
0/21)42/-223+4>/4'R3&&</1/4<)4'(/-.(3/=/>/4')5?)'(>/-2*0/>/4'-4<
.)4530>-'3)4.03'/03-B

STUWXYZ[\Y]^ZY_`[X]aUXbc[dZ][X][efghgijXUk[YdZ][X][l

jXUk[Y
m[]ZT\]
nT\ojXUk[Y
m[]ZT\]
n[^
m[]ZT\]
pq[UXcc
r[]sT\][
t[]Ypq[UXccr[]sT\][^_[\
uT\vZUwXYZT\Z]r[xaZU[y
zK
zK
{)
zK
|ERO2Bz)4530>-'3)4
zK
{)47zKM{)47
@}
{)
@K
|ERO2Bz)4530>-'3)4
zK
{)'/=-&*-'/<
{)
@K
@K
{)47zKM{)47
@}M4)'
/=-&*-'/<
{)
@K
~}
{)47zKM{)47
@}M4)'
/=-&*-'/<
{)
~}
}).*>/4'/<-'&/-2')4./|E
RO2B50)>?-2/&34/
@}
%49
/2)0{)
@}
4)103)0~};@K)0zK
%49
@}
/2)0{)
@}
%49
%49
/2
@}

~//KHzA~LCBC>-4*2.031'5)05*0'(/0</'-3&2)4R(-'32/=3</4./)5-4/R&/23)4B

A4/:./1'3)4-&.30.*>2'-4./2;*4/*3=).-&10)+0/223)4344)47'-0+/'&/23)42>-9?/
-../1'/<-2<32/-2/10)+0/223)4B
{)'/@-'3/4'2R3'(-+&)?-&</'/03)0-'3)4)5(/-&'(2'-'*20/*3034+<32.)4'34*-'3)4)5
'0/-'>/4'R3'()*')?/.'3=//=3</4./)5<32/-2/10)+0/223)4-''(-''3>/2()*&<?/
0/1)0'/<-26
H=/09/55)0'2()*&<?/>-</')<).*>/4''(/
)?/.'3=/10)+0/223)4/=/4-5'/0<32.)4'34*-'3)4)5'0/-'>/4'B
STUWXYZ[\Y]^ZY_nT\o`[X]aUXbc[dZ][X][efghginT\ojXUk[YdZ][X][l

nT\ojXUk[Ym[]ZT\]
n[^m[]ZT\]
pq[UXccr[]sT\][
zK
{)
zK
{)47zKM4)47@}
{)
{)47zKM4)47@}
{)'-&&/=-&*-'/<
{)
4)'/=-&*-'/<
4/*3=).-&@}
/2)0{)
@}
F
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'
)*+
,-
.
012&3456&2&3,-78+9:*;*::*<2=*:0+>?@A*<8+*?+*7;2:&2&3>?:B*><8+*?+*+8&C*D-8+
8&C:*?+8&BA'E+*<?+?&*&<928&>;2:?++*++F*&>2;*;;8C?C'8&+2F*>:8?A++2>2?++8B&
>G8+C?>*B2:'HG*&&2A*+82&+C?&@*F*?+E:*<8+&2>?<=8+*<
IJKIKL-E:?>82&2;5*+92&+*
-E:?>82&2;2=*:?AA:*+92&+*NOG*<E:?>82&2;2=*:?AA:*+92&+*8+F*?+E:*<;:2F>G*>8F*
F*?+E:*F*&>C:8>*:8??:*F*>;2:452:,5PHG8CG*=*:8+;8:+>:*C2:<*<QE&>8A>G*;8:+>
<?>*>G?>:*CE::*&>2:9:2B:*++8=*<8+*?+*8+2@R*C>8=*A'<2CEF*&>*<P>?S8&B?+:*;*:*&C*
;2:9:2B:*++8=*<8+*?+*>G*+F?AA*+>F*?+E:*F*&>+:*C2:<*<+8&C*>G*>:*?>F*&>+>?:>*<QK
OG*<E:?>82&2;2=*:?AA458+F*?+E:*<;:2F>G*>8F*F*?+E:*F*&>C:8>*:8??:*;8:+>F*>
;2:45E&>8A>G*;8:+><?>*>G?>9:2B:*++8=*<8+*?+*8+2@R*C>8=*A'<2CEF*&>*<K

-E:?>82&2;+>?@A*<8+*?+*ND>?@A*<8+*?+*8+F*?+E:*<;:2F>G*+>?:>2;>G*>:*?>F*&>
E&>8A>G*C:8>*:8?;2:9:2B:*++82&?:*F*>T>?S8&B?+:*;*:*&C*>G*+F?AA*+>F*?+E:*F*&>+
:*C2:<*<+8&C*>G*>:*?>F*&>+>?:>*<T8&CAE<8&B>G*@?+*A8&*F*?+E:*F*&>+K
IJKIKU,:2B:*++82&3V:**DE:=8=?A
,:2B:*++82&3;:**+E:=8=?AP,VDQ8+<*;8&*<?+>G*<E:?>82&2;>8F*;:2F+>?:>2;>:*?>F*&>
>2>8F*2;9:2B:*++82&2:<*?>GTHG8CG*=*:2CCE:+;8:+>K
IJKIKWX=*:?AADE:=8=?A
X=*:?AA+E:=8=?APXDQ8+<*;8&*<?+>G*<E:?>82&2;>8F*;:2F+>?:>2;>:*?>F*&>>2>8F*2;
9:2B:*++82&2:<*?>GY
ZZ[]^_^`abc`_defgh^b_i`a
OG*8&+>8>E>82&?A<?>?@?+*,-jD64X5kH8AA@*E+*<?+>G**A*C>:2&8CC?+*:*92:>;2:F;2:>G8+
9:2>2C2AK,:2>2C2A+9*C8;8C<?>??&<?<=*:+**=*&>+H8AA@*C?9>E:*<8&>2,-jD64X5kK
Zl[m_^_dm_dh^nhcemd]a`^_dcem
Zl[Z mopqr]stuvwgawqxyuwot
OG8+8+?+8&BA*38&+>8>E>82&T+8&BA*?:F9G?+*zz+>E<'KOG*9:8F?:'*&<928&>2;>G8++>E<'8+
2=*:?AA:*+92&+*:?>*E+8&B5k4zDOIKIC:8>*:8?KOG*:*+92&+*H8AA@**=?AE?>*<?;>*:>H2C'CA*+
2;>G*:?9'?&<*=*:'{H**S+>G*:*?;>*:K
D*C2&<?:'*&<928&>+?:*<8+*?+*C2&>:2A:?>*P<*;8&*<?+>G*:?>*2;C2F9A*>*:*+92&+*|9?:>8?A
:*+92&+*|+>?@A*<8+*?+*QT2=*:?AA+E:=8=?AT9:2B:*++82&3;:**+E:=8=?AT+?;*>'?&<>2}8C8>'?&<
<E:?>82&2;:*+92&+*Kk}9A2:?>2:'*&<928&>+8&CAE<*C2::*A?>82&2;:*+92&+*H8>GF2A*CEA?:
F?:S*:+8&CAE<8&B+*C2&<?:'FE>?>82&+K
~{
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
&'(' *+,-./*12/345567+.8+9/
:;<=>?;@<ABC<DE@FGBBCH=IIBJAC<KBJ=DBBDL@I@<A=C;=H<A=CMNCLB<KBOPQK@DGBBC
JBLI@HBJRSB;I@C<=@LLHTB>UBV@IT@GIB;@<ABC<DSA<KWXYZET<@<A=CD@<OPQM[BB\;BL<<=
@LLHTB=CB<=<S=;@<ABC<D;BHE=C<KM]C@JJA<A=CRSB;I@C<=BCH=II^;@<ABC<DSA<K_WZ>ET<@C<
`abcb@<OPQM
PKB;HAE@HFBCJ;=AC<=d<KBD<TJFAD=VBH@IIHBD;=CDBH@<BAC;@<ABC<DSA<KWXYZET<@<A=CDTDACe
ZWb]aPMPKBHBD;=CDBD<@<TDSAIIGBBV@IT@<BJ@d<BH<S=LFLIBD=d<HB@<EBC<@CJL=CdAHEBJ@<
IB@D<d=THSBBfD@d<BHMgHBD;=CDBH@<B=dh^i=HeHB@<BHS=TIJGBEB@CACedTIAC<KAD;@<ABC<
;=;TI@<A=CM[KBC<KB;H=G@GAIA<F=dHBjBL<ACe@ke==JlHBeAEBCmAMBMHBD;=CDBH@<Bnoh^ipAD
UMhURXBK@CqD
>hJBDAeCHBrTAHBD<=BC<BHh?;@<ABC<DSA<KWXYZET<@<A=CD@<<KBE@\AETE
<=IBH@<BJJ=DBm=HE@\AETE;I@CCBJJ=DBpAC<KBdAHD<D<@eBM
gE=Ce<KBDBh?;@<ABC<DSA<KWXYZET<@<A=CDRAdC=;@<ABC<HBD;=CJD<=<KB<HB@<EBC<R<KB<HA@I
SAIIGBD<=;;BJR@LLHT@ISAIIGBK@I<BJR@CJ<KBHBeAEBCSAIIGBJBLI@HBJ@DACBddBL<AVBM]d<KBHB
@HBh=HE=HBHBD;=CDBD@E=Ce<KBdAHD<h?;@<ABC<D<HB@<BJ@<OPQRsE=HB;@<ABC<DSAIIGB
BC<BHBJAC<KBD<TJF<=HB@LK@<=<@I=d>U;@<ABC<D@<<KBOPQM[A<K>U;@<ABC<DR<KBHBD;=CDB
H@<BL@CGBBD<AE@<BJSA<K@D<@CJ@HJBHH=HC=I@HeBH<K@CUMhh>M
XAVBC<KBDE@IICTEGBH=d;@<ABC<DmdAVBpSA<K_WZ>ET<@C<`abcb<K@<SAIIGBBCH=IIACe=C
<KAD;H=<=L=IR<KBHB@HBC=AC<BHAED<=;;ACeHTIBDd=HBddAL@LFd=H<KBDB;@<ABC<DMPKBDB;@<ABC<D
SAIIGBL=CDAJBHBJSA<K<KBHBD<=d<KBeH=T;d=H<=\ALA<F@DDBDDEBC<RGT<BddAL@LF@DDBDDEBC<SAII
GBL@ILTI@<BJDB;@H@<BIFM
QTHACe<KBB\;@CDA=CL=K=H<R@<@CF<AEBAd<KBQcPH@<B@E=Ce;@<ABC<D<HB@<BJ@<<KBOPQJ=DB
B\LBBJDtUiRSBSAIID<=;<KB@LLHT@I@<LTHHBC<J=DBIBVBI@CJBCH=II<KBHBD<=d;@<ABC<DAC<=<KB
CB\<I=SBHJ=DBIBVBIAd<KBLTHHBC<J=DBADC=<J=DBIBVBIu>M
&'(v 4w+.xy1yz{|w}-z1w9y
h>MtMhWV@IT@<A=C=dP=\ALA<F
gII;@<ABC<DSK=HBLBAVBJAGHT<ACAGSAIIGBBV@IT@GIBd=H<=\ALA<FdH=E<KB<AEB=d<KBAH
dAHD<<HB@<EBC<SA<KAGHT<ACAG
h>MtM>WV@IT@<A=C=dZBD;=CDB
gII;@<ABC<DACLITJBJAC<KBD<TJFETD<GB@DDBDDBJd=HHBD;=CDB<=<HB@<EBC<RBVBCAd<KBHB
@HBE@j=H;H=<=L=I<HB@<EBC<JBVA@<A=CD=HAd<KBF@HBACBIAeAGIBMW@LK;@<ABC<SAIIGB
@DDAeCBJ=CB=d<KBd=II=SACeL@<Be=HABDhpL=E;IB<BHBD;=CDBR>p;@H<A@IHBD;=CDBRtp
D<@GIBJADB@DBR?p;H=eHBDDAVBJADB@DBR^pB@HIFJB@<KdH=EE@IAeC@C<JADB@DBRspB@HIF
JB@<KdH=E<=\ALA<FRpB@HIFJB@<KGBL@TDB=d=<KBHL@TDBR=HpTCfC=SCmC=<@DDBDD@GIBR
ACDTddALABC<J@<@RDTLK@DAd@;@<ABC<JH=;D=T<B@HIFd=H<=\ALA<FGBd=HBHBD;=CDB
BV@IT@<A=CpMZBD;=CDBSAIIGB@DDBDDBJGFZWb]aPhMhLHA<BHA@M
t
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
&''()*+,-.*/,0*12+(3,**+,,'/4/5/'/*678/*,8/..098,7,/:,91*;963,9/7.*/(01+(;'9
5,/07';9,9/0*+,3./0.0.'61/1()*+,8,1-(01,8.*,<=.*/,0*1/08,1-(01,7.*,4(8/,1>?@
1+(;'95,7(01/9,8,9*(+.:,.*8,.*3,0*)./';8,A9/1,.1,-8(48,11/(0B<C+;1D.0/07(88,7*
*8,.*3,0*17+,9;',(898;4.93/0/1*8.*/(09(,10(*8,1;'*/0,E7';1/(0)8(3*+,.0.'61/1
()*+,8,1-(01,8.*,<=8,7/1,9,)/0/*/(01)(87.*,4(8/,1>?@2/''5,-8(*(7('1-,7/)/7<
&''7(07';1/(011+(;'95,5.1,9(0.'','/4/5',-.*/,0*1<F;5.0.'61,13.6*+,05,
-,8)(83,9(0*+,5.1/1().1;51,*()-.*/,0*1D,E7';9/04*+(1,)(82+(33.G(8-8(*(7('
9,:/.*/(01+.:,5,,0/9,0*/)/,9AHHD,.8'69,.*+9;,*((*+,88,.1(01D,.8'6
9/17(0*/0;.*/(0()*8,.*3,0*D3.G(8-8(*(7(':/('.*/(01D,*7<B<I(01/9,8.*/(02/''5,4/:,0
*(8,-'.7,3,0*()-.*/,0*12+(9/17(0*/0;,*8,.*3,0*,.8'6)(88,.1(01(*+,8*+.0
-8(48,11/:,9/1,.1,(8*(E/7/*6<

>J
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&&'()*+%
&'-./-0%(1'23%3421-*3'-*%
'1/6&789:8;<=>72?<?@A2><B7
C<8=:9ADE&789:8;<=>72><B7
FGHIJ
KJLMGNOPNQRL
SJGMJRP
KJLMGNOPNQR
T
UQGVHWHMPNXNPYZ[\WWYHMPNXJ]H^WJ
PQMHGGYQRHWWOGJ_INLJHLJ
OJG`QGVHRMJaNPbQ\PGJLPGNMPNQRZ
cTT UQGVHW]RQMQVOWHNRPL]RQJXNIJRMJ
Q`INLJHLJZ
dT
e^WJPQMHGGYQRRQGVHWHMPNXNPYf
VNRQGLNgRLQGLYVOPQVLQ`INLJHLJZ
c
hYVOPQVL]^\PHV^\WHPQGYZ
iJLPGNMPJINRObYLNMHWWYLPGJR\Q\L
HMPNXNPY]^\PHV^\WHPQGYHRIH^WJ
PQMHGGYQ\PaQGjQ`HWNgbPQG
LJIJRPHGYRHP\GJkll]WNgbP
bQ\LJaQGj]Q``NMJaQGjmZ
nT
UQGVHWHMPNXNPYaNPbJ``QGPfLQVJ
LNgRLQGLYVOPQVLQ`INLJHLJZ
oT
pHGJL`QGLJW`]\RH^WJPQMHGGYQR
RQGVHWHMPNXNPYQGPQIQHMPNXJaQGjZ
q
rR^JIstTuQ`PbJPNVJZ
eV^\WHPQGYHRIMHOH^WJQ`HWW
LJW`_MHGJ]^\P\RH^WJPQMHGGYQ\P
HRYaQGjHMPNXNPNJLZvOHRIH^Q\P
VQGJPbHRtTuQ`aHjNRgbQ\GLZ
wT
iJx\NGJLQMMHLNQRHWHLLNLPHRMJ]^\P
NLH^WJPQMHGJ`QGVQLPQ`bNLybJG
RJJILZ
tT
iJx\NGJLMQRLNIJGH^WJHLLNLPHRMJHRI
`GJx\JRPVJINMHWMHGJZ
z
rR^JI{tTuQ`PbJPNVJZpHOH^WJ
Q`QRWYWNVNPJILJW`_MHGJ]MQR`NRJI
PQ^JIQGMbHNGVQGJPbHRtTuQ`
aHjNRgbQ\GLZ
|T
KNLH^WJI]GJx\NGJLLOJMNHWMHGJHRI
HLLNLPHRMJZ
zT
hJXJGJWYINLH^WJI]bQLONPHWN}HPNQR
NRINMHPJIZKJHPbRQPNVVNRJRPZ
|
cTTu^JIGNIIJRZpQVOWJPJWY
INLH^WJIZpHRRQPMHGGYQRHRY
LJW`_MHGJZ~QPHWWYMQR`NRJIPQ^JI
QGMbHNGZ
qT
JGYLNMj]bQLONPHWN}HPNQRNRINMHPJIZ
KJHPbRQPNVVNRJRPZ
cT
QGN^\RI]`HPHWOGQMJLLJL
OGQgGJLLNRgGHONIWYZ
t
KJHIZ
T
KJHIZ

|c
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&'&%&()&*
-.
/01234567899:;6<=>?899@A68B@9.C2BDE@BD1FGHB@BD=1ID1B388JD?8>G@9F>=KB3
L@2B=>>828JB=>H1?8>90D1F>8IJ=1IDE818II=L1=1MIG@99M28999H1F2@128>B=F8LDBD1DN.OP1F95
Q8?RSSTUVWSXR-RYMVY.
R.
Z8>NIBA<6Z80G@235[6/DJJG@1<Q.Q=982H9@>=>DFD1I=L2@128>X9H1F2@128>.O
P1F95Q8?RSS\UVWYX-V]^M\S.
V.
Q=_4<6;H`M/643=1FJ>@I8>B<68B@9.a8LDBD1DN=>2@>N=J9@BD1MJ@29DB@b89D1
JH9G=1@>0@?81=2@>2D1=G@.OP1F95Q8?RSSYUV]-XYT^MW^.
T.
<8cHDIB/[6`@1F5d6`@G@G=B=O68B@9.e3@I8fff<BH?0=LCL@BD1DN=>dDIJ9@BD1
e9HIe8G8B>8b8?D1e@BD81BI;DB3Q8B@IB@BD2/H1FC?81=2@>2D1=G@;DB3PagAQHB@BD=1I.5
d9D1h12=9RS-VUV-XVVR^MVT.
W.
`H1dZ6Q81FK@II8>iP64=GIC[68B@9.4384^YSQGHB@BD=1D1PagA_D1@I8
2@HI8I?>HF>8IDIB@128N0D12>8@ID1FB38@LLD1DB0L=>C4e.e>=2O@B9C2@?<2Dj<C
RSS\U-SWXRS^SMW.
].
i=N@0@I3D<67=FF=1456:@0@>@G468B@9.PagAGHB@BD=1@1?>8IDIB@128=L1=1M
IG@99M28999H1F2@128>B=F8LDBD1DN.OP1F95Q8?RSSWUVWRX^\]MYR.
^.
d3=1FdA65@118eC.438cH8IBB==E8>2=G8>8IDIB@128B=PagAMB@>F8B8?B38>@JD8I
D12@128>.O@BQ8?RS-VU-YX-V\YMTSS.
\.
QD998>[C6ZD>I3[6d@?>@189568B@9.CL@BD1DNE8>IHIJ9@28N=L=>J@BD81BIKDB3
@?E@128?6G8B@IB@BD21=1MIG@99M28999H1F2@128>@LB8>L@D9H>8=L8>9=BD1DN6F8LDBD1DN6=>N=B36@1?
=18=>BK=9D18I=L238G=B38>@J0k/jlM/H1F-mX@J3@I8RNnV>@1?=GDI8?B>D@9./@128Bh12=9
RS-RU-VXWR\MV\.
Y.
Z@>BG@11546Z@@JQ6i=JJZa6/DJJZe.40>=ID18_D1@I8D13DNDB=>IM@>8ED8K=1
J3@>G@2=9=F06G8B@N=9DIG@1?ID?88LL82BI.dH>>:>HFQ8B@NRSSYU-SXT^SM\-.
-S.
d3@1J>@J@J3i6[@23D>@G=1[6A@BB@1@_@8G@_=>1e.PJD?8>G@9a>=KB3g@2B=>
A828JB=>f13DNDB=>IXCA8ED8K=LdHB@18=HIC?E8>I8PE81BI@1?Q@1@F8G81B.:8>G@B=9A8I
e>@2BRS-TURS-TX^VTRTY.
--.
<38J38>?gC6e8>8D>@5A6dDH98@1H468B@9.P>9=BD1DND1J>8ED=HI90B>8@B8?1=1MIG@99M
28999H1F2@128>.OP1F95Q8?RSSWUVWVX-RVMVR.
-R.
7DI3=JaC6Z@b3D1@IB=<C6<BH1o//6Z=IB@F8>7<.C1BDF81MIJ82DLD27M90GJ3=20B8
@2BDE@BD=1.d>DBA8EfGGH1=9RSSVURVX-TYMY^.
-V.
<3@LL8>C/6A=I81K@9?C6<B@H?B/Q./0GJ3=D?G@9DF1@12D8IXB38?@>_ID?8=L7M
2899?DLL8>81BD@BD=1.O@BA8EfGGH1=9RSSRURXYRSMVR.
-T.
<@BB8>B3K@DB8C76;DBB8hO.438>=98=L7>HB=1p
IB0>=ID18_D1@I8D17M2899
?8E89=JG81B@1?LH12BD=1X@F818BD2J8>IJ82BDE8.fGGH1=9A8ERSSSU-^WX-RSM^.
-W.
e@1q6<2388>81IZ6/D<568B@9.:DI2=E8>0=LI8982BDE8D>>8E8>IDN98D13DNDB=>IL=>
7>HB=1p
IB0>=ID18_D1@I8.d38GQ8?d38GRSS^URXW\M]-.
-].
Z8>G@1<P6a=>?=1C/6Z8>B98D1P68B@9.7>HB=1B0>=ID18_D1@I8>8J>8I81BI@
J>=GDID1FB38>@J8HBD2B@>F8BL=>B>8@BG81B=L23>=1D290GJ3=20BD298H_8GD@@1?DI8LL82BDE890
B@>F8B8?N0edfMVR^]W.79==?RS--U--^X]R\^MY].
-^.
;@1FQ/6AH98<6Q@>BD1e68B@9.4@>F8BD1F74iKDB3DN>HBD1DND1>89@JI8?=>
>8L>@2B=>0G@1B98M289990GJ3=G@.OP1F95Q8?RS-VUV]YXWS^M-].
-\.
70>?5d6gH>G@1AA6d=HB>8<P68B@9.4@>F8BD1F74iKDB3DN>HBD1DND1>89@JI8?
23>=1D290GJ3=20BD298H_8GD@.OP1F95Q8?RS-VUV]YXVRMTR.
-Y.
<GDB3456i3@B238>8IID@156/0G@1aZ68B@9.RSS]HJ?@B8=L>82=GG81?@BD=1IL=>
TR
Protocol 2014-0602 
NCT02321540


	
		
		 !"#$
%&')*'+,-&.%'/0++12'0034+-%&,52%+4*657'8.1'72'9/5*'120.7.250:452%.2'3).1'0.7';<=0.7
>72+0?@@AB?C6DEFG9?@H;
?@;
I.*'7&5)'4IJKL&'45**'MKN+35'4%*<K'%50;O'-4'*:+7*''850)5%.+724.%'4.5.7
*+0.1%)P+)4*6Q'8.*'1QI=RSL3).1'0.7'T8'4*.+7E;EU;I)4<=572'4?@@VBCH6??F9CG;
?E;
W'&57IJ;L&'1'%'4P.75%.++,%&'7)P/'4+,:5%.'7%*4'X).4'1.75:4'0.P.754Y5715
,+00+-9):%4.50+,57'-2&'P+%&'45:')%.253'7%;<=&4+7.2Z.*EVAEBED6DCA9HD;
CD
Protocol 2014-0602 
NCT02321540