A Prospective, Multicenter Clinical Trial Designed to Evaluate the Safety and Effectiveness of the XEN45 Glaucoma Treatment System in Patients With Angle Closure Glaucoma
Phase: PHASE3
Conditions: Glaucoma, Angle-Closure
Sponsor: Allergan

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 1 of 5 9 
 
 
  
 
A L L E R G A N – C O N FI D E N TI A L 
T he f oll o wi n g c o ntai ns c o nfi de ntia l, pr o prietar y i nf or mati o n  
w hic h is t he pr o pert y of Aller ga n 
St u d y Title:   
A Pr os pecti ve, M ultice nter Cli nical Trial Desi g ne d t o 
E val uate t he Safet y a n d Effecti ve ness of t he X E N 4 5 
Gla uc o ma Treat me nt S yste m i n Patie nts wit h A n gle 
Cl os ure Gla uc o ma 
Pr ot oc ol N u m ber:   
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
Pr o d uct Na me:   
X E N 4 5 Gla uc o ma Treat me nt S yste m  
De vel o p me nt P hase:  
Pi v otal  
S p o ns or:  
Aller ga n 
2 5 2 5 D u p o nt Dri ve 
Ir vi ne, Calif or nia 9 2 6 1 2 
U S A 
 
 
Ma n ufact urer: 
Aller ga n 
Safet y re p orti n g:  
I R- C LI NI C A L- S A E @ Aller ga n.c o m   
Fa x + 1- 7 1 4- 7 9 6- 9 5 0 4 or 
Bac k- u p Fa x + 1- 7 1 4- 2 4 6- 5 2 9 5 
 
Na mes a n d c o ntact i nf or mati o n of Aller g a n st u d y pers o n nel are pr o vi de d i n t he 
s u p ple me ntar y St u d y C o ntacts pa ge. Aller ga n s hall mai ntai n a n u p date d list of pri nci pal 
i n vesti gat ors, t he c o or di nati n g i n vesti gat or, i n vesti gati o nal sites, a n d ot her i nstit uti o ns 
i n v ol ve d i n t he cli nical i n vesti gati o n.
N C T 0 3 3 6 2 9 3 1

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 of 5 9 
 
 
I N V E S TI G A T O R SI G N A T U R E P A G E 
St u d y Title:  
A Pr os pecti ve, M ultice nter Cli nical Trial Desi g ne d t o 
E val uate t he Safet y a n d Effecti ve ness of t he X E N 4 5 
Gla uc o ma Treat me nt S yste m i n Patie nts wit h A n gle 
Cl os ure Gla uc o ma 
Pr ot oc ol N u m ber:  
1 9 2 4- 7 0 1- 0 0 7 
Pr ot oc ol Date:  
Oct o ber 4, 2 0 1 7 
Pr o d uct Na me:  
X E N 4 5 Gla uc o ma Treat me nt S yste m 
I n vesti gat or: 
 
St u d y L ocati o n:  
 
 
I a gree t o: 
•  I m ple me nt a n d c o n d uct t his st u d y dili ge ntl y a n d i n strict c o m plia nce wit h t his 
pr ot oc ol, G C P, a n d all a p plica ble la ws a n d re g ulati o ns. 
•  Mai ntai n all i nf or mati o n s u p plie d b y Alle r ga n i n c o nfi de nce a n d, w he n t his 
i nf or mati o n is s u b mitte d t o a n Et hics C o m mittee ( E C), or a n ot her gr o u p, it 
will be s u b mitte d wit h a desi g nati o n t hat t he material is c o nfi de ntial. 
I ha ve rea d t his pr ot oc ol i n its e ntiret y a n d I a gree t o all as pects. 
 
 
 
 
 
I n vesti gat or Pri nte d Na me  
  
Si g nat ure 
  
Date 
 
 
 
 
 
I n vesti gat or Pri nte d Na me  
  
Si g nat ure 
  
Date 
 
 
 
 
 
I n vesti gat or Pri nte d Na me  
  
Si g nat ure 
  
Date 
 
R E T U R N T O A L L E R G A N 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 of 5 9 
 
 
S y n o psis 
N U M B E R A N D TI T L E O F S T U D Y:  
1 9 2 4- 7 0 1- 0 0 7 
A Pr os pecti ve, M ultice nter Cli nical Trial Desi g ne d t o E val uate t he Safet y a n d Effecti ve ness of t he X E N 4 5 
Gla uc o ma Treat me nt S yste m i n Patie nts wit h A n gle Cl os ure Gla uc o ma 
D E V E L O P M E N T P H A S E:  Pi v otal 
S T U D Y C E N T E R S:   A p pr o xi matel y 1 5 sites i n t he Asia- Pacific a n d E ur o pea n U ni o n re gi o ns 
N U M B E R O F P A TI E N T S:   A p pr o xi matel y 6 5 patie nts will be u nilaterall y i m pla nte d wit h t he X E N 4 5 
Gla uc o ma Treat me nt S yste m ( hereafter referre d t o as X E N) eit her as a sta nd-al o ne pr oce d ure or i n c o m bi nati o n 
wit h le ns e xtracti o n. A s u bset of t his p o p ulati o n will i ncl u de a ma xi m u m of 1 0 p ha kic patie nts (ie, will n ot 
u n der g o le ns e xtracti o n at ti me of X E N s ur ger y) a n d 1 0 patie nts wit h a hist or y of tra bec ulect o m y or gla uc o ma 
s h u nt i m pla ntati o n, t o all o w f or a re prese ntati ve a n gle cl os ure gla uc o ma ( A C G) patie nt p o p ulati o n i n t he st u d y. 
O B J E C TI V E S:    
T he p ur p ose of t he trial is t o e val uate t he safet y a n d i n tra oc ular press ure (I O P)-l o weri n g effecti ve ness of X E N i n 
u p t o 6 5 patie nts wit h A C G.  
St u d y desi g n:    
T his is a pr os pecti ve, m ultice nter, si n gle-ar m, o pe n-la bel cli nical trial t o e val uate t he safet y a n d I O P-l o weri n g 
effecti ve ness of X E N i n patie nts wit h A C G.  
DI A G N O SI S A N D C RI T E RI A F O R I N C L U SI O N/ E X C L U SI O N:   
A d ult patie nts wit h A C G wit h u nc o ntr olle d I O P after ha vi n g  faile d pre vi o us me dical a n d/ or s ur gical treat me nts. 
If b ot h e yes q ualif y f or i ncl usi o n, t he n t he e ye wit h t he hi g her I O P at baseli ne will be t he st u d y e ye. If b ot h e yes 
q ualif y f or i ncl usi o n a n d ha ve t he sa me baseli ne I O P, t he n t he ri g ht e ye will be t he st u d y e ye. 
K E Y I N C L U SI O N:  
•  Dia g n osis of A C G defi ne d as areas of iri d otra bec ular c o ntact prese nt i n ≥ 2 q ua dra nts a n d gla uc o mat o us 
da ma ge t o o ptic disc a n d vis ual fiel d, i n t he st u d y e ye.  
N ote: Pr oce d ures t o wi de n t he iri d oc or neal a n gle i n t he tar get q ua dra nt (e g, g o ni os y nec hial ysis, le ns 
e xtracti o n [clear le ns e xtracti o n or  cataract s ur ger y/ p hac oe m ulsificati o n], a n d i ntra oc ular le ns [I O L] 
place me nt) are per mitte d o n t he o perati ve da y ( Da y 1)  at t he i n vesti gat or’s discreti o n; h o we ver, all 
pr oce d ures m ust be s uccessf ul a n d u nc o m plicate d f or patie nts t o recei ve X E N. A ma xi m u m of 
a p pr o xi matel y 1 0 p ha kic patie nts (ie, will n ot u n der g o le ns e xtracti o n at ti me of X E N s ur ger y) is all o we d 
i n t he st u d y. 
•  I n t he o pi ni o n of t he i n vesti gat or, t he I O P is u nc o ntr olle d i n t he st u d y e ye after ha vi n g faile d pre vi o us 
me dical a n d/ or s ur gical treat me nt (e g, t o pical I O P-l o weri n g me dicati o ns, laser peri p heral iri d ot o m y, le ns 
e xtracti o n, gla uc o ma s h u nt i m pla ntati o n, tra bec ulect o m y) 
•  I O P of ≥ 2 0 m m H g a n d ≤ 3 5 m m H g b y G ol d ma n n a p pla nati o n t o n ometr y i n t he st u d y e ye at scree ni n g 
a n d baseli ne ( H o ur 0) 
•  St u d y e ye has healt h y, free, a n d m o bile  c o nj u ncti va i n t he tar get q ua dra nt 
•  Gla uc o mat o us vis ual fiel d l oss wit h a mea n de viati o n sc ore of at least - 1  d B i n t he st u d y e ye t hat, i n t he 
o pi ni o n of t he i n vesti gat or, is n ot f u ncti o nall y si g nifica nt (e g, s plit fi xati o n, fiel d defect wit hi n t he ce ntral 
1 0 de grees t hat is vis uall y si g nifica nt or li kel y t o  ca use ce ntral vis ual i m pair me nt u p o n pr o gressi o n are 
e xcl u de d) 
K E Y E X C L U SI O N:  
•  
K n o w n hist or y of blee di n g dis or der or pr ol o n ge d blee di n g after s ur ger y (i n t he o pi ni o n of t he 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 of 5 9 
 
 
i n vesti gat or) or t h ose o n p har mac ol o gic bl o o d t hi n ners ot her t ha n as piri n ( u p t o 1 0 0 m g/ da y)  
•  
Hist or y of der mat ol o gic kel oi d f or mati o n 
Ke y Oc ular Criteria f or E xcl usi o n 
•  
O pe n a n gle gla uc o ma, acti ve ac ute a n gle cl os ure attac k, c o n ge nital gla uc o ma, j u ve nile gla uc o ma, 
sec o n dar y gla uc o ma (e g, a nteri or s u bl u xati o n of t he le ns, iris or ciliar y b o d y c ysts, acti ve iris a n d a n gle 
ne o vasc ularizati o n, iri d oc or neal e n d ot helial s y n dr o me , a nteri or u veitis, dr u g-i n d uce d) i n t he st u d y e ye 
•  
Hist or y of f oll o wi n g s ur geries i n t he st u d y e ye 
o  
i ncisi o nal refracti ve s ur ger y (e g, ra dial kerat ot o m y), ot her t ha n asti g matic kerat ot o m y or li m bal 
rela xi n g i ncisi o ns 
o  
c or neal graft i ncl u di n g partial grafts s uc h as Desce met’s stri p pi n g e n d ot helial kerat o plast y a n d 
Desce met’s me m bra ne e n d ot helial kerat o plast y  
o  
pre vi o us laser or i ncisi o nal i ntra oc ular s ur ger y  t hat mi g ht i nterfere wit h t he o utc o me of t his trial 
H o we ver, pre vi o us i ncisi o nal a n d laser gla uc o ma  s ur geries (e g, tra bec ulect o m y, gla uc o ma s h u nt 
i m pla ntati o n, laser tra bec ul o plast y, iri d ot o m y, cili oa blati ve pr oce d ures) or u nc o m plicate d 
p hac oe m ulsificati o n wit h I O L, occ urri n g m ore t ha n 3 m o nt hs pri or t o scree ni n g, are all o we d i n t he 
st u d y e ye. A ma xi m u m 1 0 patie nts wit h a hist or y of tra bec ulect o m y or gla uc o ma s h u nt i m pla ntati o n 
(a wa y fr o m t he tar get q ua dra nt) is all o we d i n t his st u d y.  
•  
Pre vi o us gla uc o ma s h u nt i m pla ntati o n i n t he tar get q ua dra nt i n t he st u d y e ye 
•  
Vis uall y si g nifica nt cataract (ie, B C V A 2 0/ 4 0 S nelle n e q ui vale nt usi n g L o g Mar c hart at scree ni n g a n d 
baseli ne) i n t he st u d y e ye t hat will n ot be re m o ve d at t he ti me of X E N i m pla ntati o n  
•  
St u d y e ye wit h best-c orr ecte d vis ual ac uit y ( B C V A) w orse t ha n  2 0/ 1 0 0 ( S nelle n e q ui vale nt usi n g 
L o g Mar c hart) at scree ni n g a n d baseli ne; fell o w ( n o n-st u d y) e ye wit h B C V A w orse t ha n 2 0/ 2 0 0 at 
scree ni n g a n d baseli ne. A patie nt wit h a cataract i n t he st u d y e ye a nd B C V A w orse t ha n 2 0/ 1 0 0 i n t he 
st u d y e ye ma y be i ncl u de d if, i n t he o pi ni o n of t he i n vesti gat or, t he patie nt is li kel y t o ha ve B C V A of 
2 0/ 4 0 or better after cataract s ur ger y t hat will be  perf or me d at t he ti me of X E N i m pla ntati o n.  
T E S T P R O D U C T A N D M O D E O F A D MI NI S T R A TI O N: 
X E N 4 5 Gla uc o ma Treat me nt S yste m, a b i nter n o  s ur gical a p pr oac h a n d i mpla ntati o n. X E N 4 5 Gla uc o ma 
Treat me nt S yste m is c o m prise d of t he X E N Gel I m pla nt (als o referre d t o as Gel I m pla nt) a n d X E N I nject or (als o 
referre d t o as I nject or). T he X E N I nject or is a sterile, si n gle use mec ha nical deli ver y s yste m f or t he X E N Gel 
I m pla nt. T he nee dle of t he sterile X E N I nject or prel oa de d wit h t he X E N Gel I m pla nt is a d va nce d t hr o u g h t he 
peri p heral c or nea a n d acr oss t he a nteri or c ha m ber (ie, a b i nter n o ) t o war d t he tar get q ua dra nt. 
D U R A TI O N O F S T U D Y:   Scree ni n g peri o d: 6 0 da ys. F oll o w- u p Peri o d: 1 2 m o nt hs after de vice i m pla ntati o n. 
R E S P O N S E M E A S U R E S: 
Effecti ve ness:  
•  I O P ( H o ur 0) meas ure d b y G ol d ma n n a p pla nati o n t o n o metr y 
•  N u m ber of c o nc o mita nt I O P-l o weri n g me dicati o ns 
He alt h O utc o me Me as ures:  
Patie nt oc ular s y m pt o m q uesti o n naire   
S afet y:  
Safet y assess me nts i ncl u de a d verse e ve nts ( A Es), pre g na nc y test a n d oc ular para meters as deter mi ne d t hr o u g h 
assess me nts of vis ual ac uit y, vis ual fiel d, pac h y metr y, bi o micr osc o pic slit la m p, g o ni osc o p y, a n d 
o p ht hal m osc o pic e xa mi nati o ns  

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 of 5 9 
 
 
S T A TI S TI C A L M E T H O D S: 
S a m ple Size C alc ul ati o n:  
Fift y patie nts will pr o vi de a precisi o n of at least ± 0. 1 4 5 t o esti mate t he pr o p orti o n of patie nts ac hie vi n g a n I O P 
re d ucti o n ≥ 2 0 % at 1 2 m o nt hs o n t he sa me n u m ber or fe wer I O P-l o weri n g me dicati o ns c o m pare d wit h baseli ne 
base d o n a 9 5 % e xact Cl o p per- Pears o n CI f or bi n o mial pr o p orti o ns. Si xt y-fi ve patie nts will be i m pla nte d t o 
e ns ure at least 5 0 e val ua ble patie nts wit h 1 2 m o nt hs of f oll o w- u p.  
St u d y P o p ul ati o n: 
I m pl a nte d p o p ul ati o n: T he i m pla nte d p o p ulati o n will i ncl u de all patie nts i m pla nte d wit h X E N. T his p o p ulati o n 
will be use d f or all pri mar y a n d sec o n dar y eff ecti ve ness a nal yses a n d all safet y a nal yses. 
Effecti ve ness: 
Pri mar y Effecti v e ness A nal ysis 
T he pri mar y effecti ve ness a nal ysis will esti mate t he pr o p orti o n of patie nts, wit h c orres p o n di n g 2-si de d 9 5 % CI, 
t hat ac hie ve at least a 2 0 % re d ucti o n fr o m baseli ne H o ur 0 I O P w hile o n t he sa me n u m ber or fe wer I O P-
l o weri n g me dicati o ns at M o nt h 1 2 c o m pare d wit h baseli ne usi n g a re peate d meas ures l o gistic re gressi o n m o del. 
T he m o del will i ncl u de visit a n d baseli ne I O P as fi xe d effects wit h data fr o m M o nt hs 1, 3, 6, 8, 1 0, a n d 1 2. T he 
pri mar y effecti ve ness a nal ysis will be perf or me d usi n g t he i m pla nte d p o p ulati o n. 
Sec o n dar y Effecti ve ness A nal yses 
T he mea n a n d 2-si de d 9 5 % CI f or ra w I O P wit h t he c orres p o n di n g c ha n ge fr o m baseli ne will be esti mate d usi n g 
a mi xe d-effects m o del f or re peate d m eas ure me nts i ncl u di n g all p ost- baseli ne visits wit h visit a n d baseli ne I O P 
as fi xe d effects. A d diti o nall y, t he n u m ber of I O P-l o weri n g me dicati o ns will be s u m marize d b y visit wit h 
descri pti ve statistics ( mea n, sta n dar d de viati o n, mi ni m u m, ma xi m u m) a n d 2-si de d 9 5 % CI f or t he mea n. T he 
sec o n dar y effecti ve ness a nal yses will be perf or me d usi n g t he i m pla nte d p o p ulati o n. 
S afet y:  
Safet y a nal yses will be perf or me d usi n g t he i m pla nte d p o p ulati o n. T he n u m ber a n d perce nta ge of patie nts 
re p orti n g A Es will be ta b ulate d re gar dless of ca usalit y. A Es, a d verse de vice effects ( A D Es), B C V A, li ne c ha n ge 
i n B C V A fr o m baseli ne, bi o micr osc o pic slit la m p, a n d o p ht hal m osc o p y fi n di n gs will be s u m marize d b y 
fre q ue ncies at eac h visit.  
 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 6 of 5 9 
 
 
 
Ta ble of C o nte nts 
T itle Pa ge .................................................................................................................................. 1 
S y n o psis  .................................................................................................................................... 3 
T a ble of C o nte nts  ...................................................................................................................... 6  
List of Ta bles  ............................................................................................................................. 9  
List of Fi g ures  ........................................................................................................................... 9  
1.   A b bre viati o ns a n d Ter ms  ................................................................................................. 1 2  
2.   Bac k gr o u n d, Ris k a n d Be nefit, a n d Cli nical Rati o nale  ................................................... 1 3  
2. 1  
Bac k gr o u n d  ............................................................................................................ 1 3  
2. 2  
Ris k a n d Be nefit  ..................................................................................................... 1 7  
2. 3  
Cli nical Rati o nale  ................................................................................................... 1 7  
3.   St u d y O bjecti ves a n d Cli nical H y p ot heses  ...................................................................... 1 7  
3. 1  
St u d y O bjecti ves  .................................................................................................... 1 7 
3. 2  
Cli nical H y p ot heses  ............................................................................................... 1 8 
4.   St u d y Desi g n  .................................................................................................................... 1 8  
4. 1  
Str uct ure  ................................................................................................................. 1 8  
4. 2  
D urati o n  ................................................................................................................. 1 8  
4. 3  
Treat me nt Gr o u ps a n d Treat me nt Re gi me n  ........................................................... 1 8  
4. 3. 1   St u d y Treat me nt  ......................................................................................... 1 8  
4. 3. 2   Met h o ds f or Mas ki n g  ................................................................................. 1 8  
4. 4  
Per missi ble a n d Pr o hi bite d Me dicati o ns/ Treat me nts  ............................................. 1 8  
4. 4. 1   Per missi ble Me dicati o ns/ Treat me nts  ......................................................... 1 8  
4. 4. 2   Pr o hi bite d Me dicati o ns/ Treat me nts  ........................................................... 2 0  
5.   St u d y P o p ulati o n  .............................................................................................................. 2 1  
5. 1  
N u m ber of Patie nts  ................................................................................................. 2 1  
5. 2  
St u d y P o p ulati o n C haracteristics  ........................................................................... 2 1 
5. 3  
I ncl usi o n Criteria .................................................................................................... 2 2  
5. 4  
E xcl usi o n Criteria  .................................................................................................. 2 3  
6.   Pr oce d ures  ........................................................................................................................ 2 6  
6. 1  
Pr oce d ures t o be Perf or me d  ................................................................................... 2 6  

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 7 of 5 9 
 
 
6. 1. 1   Scree ni n g Visit  ........................................................................................... 2 6  
6. 1. 2   Baseli ne Visit  ............................................................................................. 2 8  
6. 1. 3   O perati ve Visit ( Da y 1)  .............................................................................. 2 9  
6. 1. 4   F oll o w- u p E xa mi nati o ns a n d Cli nical Para meters  ..................................... 3 3  
6. 1. 5   1 2- M o nt h P ost o perati ve Visit/ Earl y E xit Visit  ........................................... 3 4  
6. 2  
I nstr ucti o ns f or t he Patie nts .................................................................................... 3 5  
6. 3  
U nsc he d ule d Visits  ................................................................................................. 3 5  
6. 4  
Earl y Disc o nti n uati o n of Patie nts  .......................................................................... 3 6  
6. 5  
Wit h dra wal Criteria  ................................................................................................ 3 6  
7.   Res p o nse Meas ures a n d S u m mar y of Data C ollecti o n Met h o ds  ..................................... 3 7  
7. 1  
Effecti ve ness Meas ures  .......................................................................................... 3 7  
7. 2  
Safet y Meas ures  ..................................................................................................... 3 7  
7. 3  
Healt h O utc o me Meas ures  ..................................................................................... 3 9  
7. 4  
S u m mar y of Met h o ds of Data C ollecti o n  .............................................................. 3 9  
8.   Statistical Pr oce d ures  ....................................................................................................... 3 9  
8. 1  
A nal ysis P o p ulati o ns  .............................................................................................. 3 9  
8. 2  
C ollecti o n/ Deri vati o n of Pri mar y a n d Sec o n dar y Effecti ve ness Assess me nts  ...... 4 0  
8. 2. 1   Pri mar y Effecti ve ness Varia ble  .................................................................. 4 0  
8. 2. 2   Sec o n dar y Effecti ve ness Varia bles  ............................................................. 4 0  
8. 2. 3   Ot her Effecti ve ness Varia bles  .................................................................... 4 0 
8. 3  
H y p ot hesis a n d Met h o ds of A nal ysis  ..................................................................... 4 1  
8. 3. 1   Pri mar y Effecti ve ness A nal yses  ................................................................. 4 1  
8. 3. 2   Sec o n dar y Effecti ve ness A nal yses  ............................................................. 4 1  
8. 3. 3   Ot her Effecti ve ness A nal yses  ..................................................................... 4 1  
8. 3. 4   Safet y A nal yses  .......................................................................................... 4 2  
8. 4  
S u b gr o u p A nal yses  ................................................................................................. 4 2  
8. 5  
Sa m ple Size Calc ulati o n  ........................................................................................ 4 2  
8. 6  
I nteri m A nal yses .................................................................................................... 4 2  
9.   Materials  .......................................................................................................................... 4 3  
9. 1  
St u d y Treat me nt  ..................................................................................................... 4 3  
9. 1. 1   Pr o d uct Descri pti o n  .................................................................................... 4 3  
9. 1. 2   I nstr ucti o ns f or Use a n d A d mi nistrati o n .................................................... 4 3  
9. 2  
Ot her St u d y S u p plies  .............................................................................................. 4 4  
1 0.   St u d y A d mi nistrati o n Pr oce d ures  .................................................................................... 4 4  

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 8 of 5 9 
 
 
1 0. 1   Patie nt E ntr y Pr oce d ures  ........................................................................................ 4 4  
1 0. 1. 1   O ver vie w of E ntr y Pr oce d ures  ................................................................... 4 4  
1 0. 1. 2   I nf or me d C o nse nt a n d Patie nt Pri vac y ....................................................... 4 5  
1 0. 1. 3   Met h o d f or Assi g n me nt t o Treat me nt Gr o u ps  ............................................ 4 6  
1 0. 2   C o m plia nce wit h Pr ot oc ol  ...................................................................................... 4 6  
1 0. 3   Pre g na nc y  ............................................................................................................... 4 6  
1 0. 4   St u d y Ter mi nati o n  .................................................................................................. 4 7  
1 1 .  A d verse E ve nts  ................................................................................................................ 4 7  
1 1 . 1  Defi niti o ns  .............................................................................................................. 4 8  
1 1. 1. 1   A d verse E ve nt  ............................................................................................ 4 8  
1 1. 1. 2   Seri o us A d verse E ve nt  ............................................................................... 4 9  
1 1. 1. 3   A d verse De vice Effect  ............................................................................... 4 9 
1 1. 1. 4   Seri o us A d verse De vice Effect  ................................................................... 4 9  
1 1. 1. 5   U na ntici pate d Seri o us A d verse De vice Effect  ........................................... 5 0  
1 1. 1. 6   De vice Deficie nc y  ...................................................................................... 5 0  
1 1. 1. 7   Se verit y  ...................................................................................................... 5 0 
1 1. 1. 8   Relati o ns hi p t o De vice or Pr oce d ure .......................................................... 5 0 
1 1 . 2  Ti meli nes f or Re p orti n g  ......................................................................................... 5 1  
1 1 . 3  Pr oce d ures f or Re p orti n g a n A E or A D E  ............................................................... 5 1  
1 1 . 4  Pr oce d ures f or Re p orti n g a n S A E or S A D E  .......................................................... 5 1  
1 2.   A d mi nistrati ve Iss ues  ....................................................................................................... 5 2  
1 2. 1   Pr otecti o n of H u ma n Patie nts  ................................................................................ 5 2  
1 2. 1. 1   C o m plia nce wit h I nf or me d C o nse nt Re g ulati o ns  ...................................... 5 2  
1 2. 1. 2   C o m plia nce wit h E C Re g ulati o ns  .............................................................. 5 2  
1 2. 1. 3   C o m plia nce wit h G o o d Cli nical Practice  ................................................... 5 3  
1 2. 1. 4   C o m plia nce wit h Electr o nic Rec or ds a n d Si g nat ure Re g ulati o ns  ............. 5 3  
1 2. 2   C ha n ges t o t he Pr ot oc ol  ......................................................................................... 5 3 
1 2. 3   Patie nt C o nfi de ntialit y a n d Pri vac y  ....................................................................... 5 3 
1 2. 4   D oc u me ntati o n  ....................................................................................................... 5 4  
1 2. 4. 1   S o urce D oc u me nts  ..................................................................................... 5 4 
1 2. 4. 2   Case Re p ort F or m C o m pleti o n  .................................................................. 5 5  
1 2. 4. 3   I n vesti gat or Re p orts ................................................................................... 5 5  
1 2. 4. 4   Rete nti o n of D oc u me ntati o n  ...................................................................... 5 5  
1 2. 5   La beli n g, Pac ka gi n g, St ora ge, a n d Ret ur n of St u d y De vices  ................................. 5 6  

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 9 of 5 9 
 
 
1 2. 5. 1   La beli n g/ Pac ka gi n g  .................................................................................... 5 6  
1 2. 5. 2   St ora ge of St u d y De vices  ........................................................................... 5 6  
1 2. 5. 3   St u d y De vice Acc o u nta bilit y  ...................................................................... 5 6  
1 2. 5. 4   Ret ur n of St u d y De vices  ............................................................................ 5 7 
1 2. 6   M o nit ori n g b y Aller ga n  .......................................................................................... 5 7  
1 2. 7   P u blicati o ns  ............................................................................................................ 5 7  
1 2. 8   C o or di nati n g I n vesti gat or  ...................................................................................... 5 7  
1 3.   Refere nces  ........................................................................................................................ 5 8  
1 4.   Attac h me nts  ..................................................................................................................... 5 9  
 
List of Ta bles 
T a ble 1- 1  
Sc he d ule of Visits a n d Pr oce d ures  .................................................................. 1 0  
T a ble 6 – 1  
Pre o perati ve Me dicati o ns ................................................................................ 2 9 
T a ble 6 – 2  
P ost o perati ve Me dicati o ns  .............................................................................. 3 1  
 
List of Fi g ures 
Fi g ure 6 – 1  
X E N I m pla ntati o n Pr oce d ure  .......................................................................... 3 1  
 
 

 
 
 
 
A p pr o v al  D at e: 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Treat me nt S yste m 
 
 
 
Pa ge 1 0 of 5 9 
 
 
T a ble 1- 1  
Sc he d ule of Visits a n d Pr oce d ures 
St u d y Peri o d  
Scree ni n g a  
B aseli ne 
O per ati ve 
d a y 
D a y 1 
D a y 
2 
D a y 
8 
Wee k 
2 
M o nt h 
1 
M o nt h 
3 
M o nt h 
6 
M o nt h 
8 
M o nt h 
1 0 
M o nt h 1 2/ 
E arl y e xit 
visit 
Visit Wi n d o w 
u p t o 6 0 
da ys 
Da y - 5 t o 
Da y - 7  
N A  
N A 
± 2 
da ys 
± 3 
da ys 
± 5  
da ys 
± 1 0 
da ys 
± 1 4 
da ys 
± 1 4 
da ys 
± 1 4 
da ys 
± 1 4  
da ys 
C o nse nt/ A ut h orizati o n 
X  
  
  
  
  
  
  
  
  
  
  
 
I ncl usi o n/ E xcl usi o n Criteria 
X  
X  
X  
  
  
  
  
  
  
  
  
 
Patie nt De m o gra p hics 
X  
  
  
  
  
  
  
  
  
  
  
 
Me dical/ O p ht hal mic Hist or y
b  
X  
X  
  
  
  
  
  
  
  
  
  
 
Patie nt oc ular s y m pt o m 
q uesti o n naire 
X  
  
  
  
  
  
  
X  
X  
  
  
X 
C o nc o mita nt Me dicati o ns, 
Pr oce d ures, T hera pies  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 
A d verse E ve nts 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 
Pre g na nc y Test ( Uri ne) c 
X  
X  
  
  
  
  
  
  
  
  
  
X 
St u d y Treat me nt 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
E x a mi n ati o ns:  Rec o m me n de d t o be 
perf or me d i n t he f oll o wi n g or der 
fr o m t o p t o b ott o m 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ma nifest refracti o n
d 
O U  
O U  
  
  
  
  
  
S E  
  
  
  
O U 
Best-c orrecte d vis ual ac uit y ( S nelle n 
e q ui vale nt usi n g L o g Mar) 
O U  
O U  
  
  
  
  
S E  
S E  
S E  
S E  
S E  
O U 
Vis ual Fiel d e test 
O U 
 
 
 
 
 
 
 
 
 
 
 
 
 
O U f 
Bi o micr osc o pic slit la m p 
e xa mi nati o n 
O U  
O U  
  
S E  
S E  
S E  
S E  
S E  
S E  
S E  
S E  
O U 
I ntra oc ular press ure meas ure me nt 
(t o n o metr y)g 
O U  
O U h  
  
S E  
S E  
S E  
S E  
S E  
S E  
S E  
S E  
O Uh 
Pac h y metr y 
O U  
  
  
  
  
  
  
  
  
  
  
O U 
G o ni osc o p y 
O U  
  
  
  
  
  
S E  
  
S E  
  
  
O U 
O p ht hal m osc o p y i 
O U  
O U  
  
  
  
  
S E  
S E  
S E  
  
  
O U 
N A = n ot a p plica ble; S E = st u d y e ye; O U = b ot h e yes 
a 
Scree ni n g e xa mi nati o ns ca n be c o m plete d o n m o re t ha n o ne visit wit hi n t he all o wa ble wi n d o w 
b  
 Me dical hist or y, s ur gical hist or y, o p ht hal mic hist or y, a n d o p ht hal mic s u r gical hist or y will be c ollecte d 
c  
A p plica ble t o fe males of c hil d beari n g p ote ntial 
d  
Ma nifest refracti o n will be  perf or me d d uri n g a n y visit if best-c orrecte d vis ual ac uit y ( B C V A) re d ucti o n of ≥ 2 li nes is o bser ve d si nce t he last B C V A e xa mi nati o n. 
e   
Vis ual fiel d test perf or me d u p t o 6 m o nt hs pri or t o o perati ve da y ( Da y 1) is all o we d 

 
 
 
 
A p pr o v al  D at e: 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Treat me nt S yste m 
 
 
 
Pa ge 1 1 of 5 9 
 
 
f  
If t he vis ual fiel d assess me nt at t his visit s h o ws pr o gressi o n of vis ual fiel d l oss fr om baseli ne ( defi ne d as a w orse ni n g of at  least 3 d B i n mea n de viati o n sc ore), a sec o n d vis ual 
fiel d test m ust be perf or me d wit hi n o ne wee k t o c o nfir m t he pro gressi o n. If t he sec o n d vis ual fi el d test is n ot c o nfir mat or y or is e q ui v ocal, a t hir d test m ust be perf or me d 
wit hi n a wee k t o c o nfir m res ults.  
g 
Meas ure me nt of i ntra oc ular press ure (I O P) m u st be perf or me d at H o ur 0; I O P m ust be c o m plete d pri or t o pac h y metr y, g o ni osc o p y, a n d o p ht hal m osc o p y. 
h  
Di ur nal I O P meas ure me nts: T hree I O P meas ure me nts ta ke n o ver a n ei g ht- h o ur peri o d o n t he sa me da y a p pr o xi matel y f o ur h o urs a part, at H o ur 0 ( ± 1 h o ur), H o ur 4 = H o ur 0 
+ 4 h o urs ( ± 3 0 mi n utes), a n d H o ur 8 = H o ur 0 + 8 h o urs ( ± 3 0 mi n utes) 
i  
N o n- dilate d o p ht hal m osc o p y ma y be perf or me d if t he i n vesti gat or belie ves t hat  p u pil dilati o n ma y p ut t he patie nt at ris k. W he n dilati o n is use d, o p ht hal m osc o p y s h o ul d be t he 
last e xa mi nati o n. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 1 2 of 5 9 
 
 
1.  
A b bre vi ati o ns a n d Ter ms 
Ter m/ A b bre vi ati o n 
Defi niti o n 
A C G 
a n gle cl os ure gla uc o ma 
A D E 
a d verse de vice effect 
A E 
a d verse e ve nt 
A L PI 
ar g o n laser peri p heral iri d o plast y 
B C V A 
best-c orrecte d vis ual ac uit y 
BI D 
t wice dail y 
E C 
Et hics C o m mittee 
e C R F 
electr o nic case re p ort f or m 
E D C 
electr o nic data ca pt ure 
E U 
E ur o pea n U ni o n 
F D A 
U S F o o d a n d Dr u g A d mi nistrati o n 
G C P 
G o o d Cli nical Practice 
G O N 
gla uc o mat o us o ptic ne ur o pat h y 
I C 
i nf or me d c o nse nt 
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I D F U 
i n vesti gati o nal directi o ns f or use 
I O L 
i ntra oc ular le ns 
I O P 
i ntra oc ular press ure 
I S O 
I nter nati o nal Or ga nizati o n f or Sta n dar dizati o n 
I T C 
iri d otra bec ular c o ntact 
L PI 
laser peri p heral iri d ot o m y 
O A G 
o pe n a n gle gla uc o ma 
P A C 
pri mar y a n gle cl os ure  
P A C G 
pri mar y a n gle cl os ure gla uc o ma 
P A C S 
pri mar y a n gle cl os ure s us pect 
P A S 
peri p heral a nteri or s y nec hiae 
P O A G 
pri mar y o pe n a n gle gla uc o ma 
S A D E 
seri o us a d verse de vice effect 
SI T A 
S we dis h i nteracti ve t hres h ol di n g al g orit h m 
TI D 
t hree ti mes dail y 
U S A D E 
u na ntici pate d seri o us a d verse de vice effect 
QI D 
f o ur ti mes dail y 
Q D 
o nce dail y 
W O C F 
w orst o bser va ti o n carrie d f or war d 
X E N 
X E N 4 5 gla uc o ma treat me nt s yste m  
 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 1 3 of 5 9 
 
 
2.  
B ac k gr o u n d, Ris k a n d Be nefit, a n d Cli nic al R ati o n ale 
2. 1  
B ac k gr o u n d 
Gla uc o ma is t he sec o n d lea di n g ca use of vis u al i m pair me nt a n d bli n d ness w orl d wi de a n d a 
si g nifica nt healt hcare pr o ble m, wit h a s u bsta ntial h u ma nis tic a n d ec o n o mic b ur de n t hat 
i ncreases wit h disease pr o gressi o n. M ore t ha n 7 9 milli o n pe o ple are pr ojecte d t o s uffer fr o m 
gla uc o ma b y 2 0 2 0, a n d a p pr o xi matel y 2 5 % of al l t hese cases will be a n gle cl os ure gla uc o ma 
( A C G) (Q ui gle y 2 0 0 6 ). A C G carries a hea vier b ur de n of vis ual m or bi dit y t ha n o pe n a n gle 
gla uc o ma ( O A G) ( F oster 2 0 0 2 ). T he pre vale nce of A C G differs a m o n g differe nt et h nic 
gr o u ps wit h t he hi g hest rates re p orte d i n I n uit, C hi nese, a n d ot her Asia n p o p ulati o ns 
(Marc hi ni 2 0 1 5 ). 
A C G is a gr o u p of diseases c haracterize d b y t he a p p ositi o n of t he peri p heral iris a gai nst t he 
tra bec ular mes h w or k, res ulti n g i n t he o bstr uctio n of a q ue o us o utfl o w. Base d o n t he eti ol o g y, 
a n gle cl os ure ca n be pri mar y, sec o n dar y t o a n ot her e ye disease, or dr u g-i n d uce d 
(A m erica n Ass ociati o n of O p ht hal m ol o g y 2 0 1 3 ). T he c urre nt i nter nati o nal classificati o n of 
a n gle cl os ure i ncl u des 3 c o nce pt ual sta ges c orres p o n di n g t o t he pr o gr essi o n of t he disease 
(W ei nre b 2 0 0 6). Pri mar y a n gle cl os ure s us pect ( P A C S) is c haracterize d b y iri d otra bec ular 
c o ntact (I T C), n or mal i ntra oc ular press ure (I O P ), a bse nce of peri p heral a nteri or s y nec hiae 
( P A S), a n d n o e vi de nce of gla uc o mat o us o ptic ne ur o pat h y ( G O N). Pri mar y a n gle cl os ure 
( P A C) i n v ol ves I T C res ulti n g i n raise d I O P a n d/ or P A S, a n d n o e vi de nce of G O N. Pri mar y 
a n gle cl os ure gla uc o ma ( P A C G) is defi ne d b y prese nce of I T C pl us e vi de nce of G O N; 
h o we ver, P A S a n d raise d I O P ma y be a bse nt at t he ti me of i nitial e xa mi nati o n. I n t his 
classificati o n sc he me, t he e xte nt of I T C i n eac h sta ge was ori gi nall y defi ne d t o be ≥ 3 
q ua dra nts; h o we ver, rece nt g ui deli nes ha ve re d uce d t he I T C dia g n ostic t hres h ol d t o ≥ 2 
q ua dra nts t o a v oi d u n der- dia g n osis of  patie nts al o n g t his A C G s pectr u m (W ei nre b 2 0 0 6 ; 
E ur o pea n Gla uc o m a S ociet y 2 0 1 4 ). T he gla uc o mat o us o ptic ne ur o pat h y defi ne d i n t his 
classificati o n i ncl u de str uct ural (e g, o ptic disc ) a n d f u ncti o nal (e g, vis ual fiel d) a b n or malities 
c o nsiste nt wit h gla uc o ma. I n cases w here t here is a d va nce d visi o n l oss a n d a ut o mate d 
peri metr y ca n n ot be perf or me d, gla uc o ma dia g n osis is base d o n str uct ural da ma ge t o t he 
o ptic disc. C o n versel y, i n cases w here t he o ptic  disc ca n n ot be vis ualize d, gla uc o ma ca n be 
dia g n ose d o n t he basis of vis ual ac uit y < 3/ 6 0 a n d eit her I O P > 2 4 m m H g or si g ns of 
pre vi o us filteri n g s ur ger y ( W ei nre b 2 0 0 6 ). 
Ot her classificati o ns of A C G ha ve bee n use d i n t he past, s uc h as t he su bcate g ories of ac ute, 
s u bac ute/i nter mitte nt, a n d c hr o nic, w hic h are base d o n t he prese nce or a bse nce of s y m pt o ms; 
h o we ver, a maj or fla w i n t his sc he me is t he lac k  of e m p hasis o n vis ual f u ncti o n. F urt her m ore, 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 1 4 of 5 9 
 
 
t his classificati o n ofte n assi g ns all t he s u b gr o u ps as “ gla uc o ma,” re gar dless of w het her t here 
is gla uc o mat o us o ptic ne ur o pat h y. A C G ca n als o be cate g orize d based o n t he 4 le vels of 
a nat o mic mec ha nis ms of a n gle cl os ure, i ncl u di n g, iris (e g, p u pillar y bl oc k), ciliar y b o d y (e g, 
platea u iris), le ns (e g, p hac o m or p hic), a n d p osteri or t o t he le ns (e g, mali g na nt gla uc o ma), a n d 
t his sc he me ca n be use d i n c o m bi nati o n wit h disease sta ge t o deter mi ne t he o pti mal treat me nt 
a p pr oac h.  
C urre nt A C G treat me nt c o nsists of I O P-re d uci n g laser pr oce d ures, le ns e xtracti o n, 
me dicati o ns, a n d i ncisi o nal s ur geries. T he first li ne treat me nts i n v ol ve esta blis hi n g t he tar get 
press ure, us uall y b y relie vi n g p u pillar y bl oc k us i n g laser peri p heral iri d ot o m y ( L PI) a n d/ or 
le ns e xtracti o n (Az uara- Bla nc o 2 0 1 1 ; Az uara- Bla nc o 2 0 1 6 ). W he n i n dicate d, ar g o n laser 
peri p heral iri d o plast y ( A L PI) ma y als o be use d  t o f urt her o pe n a n a p p ositi o nall y cl ose d 
a n gle. L PI al o ne is ofte n n ot effecti ve i n pre ve nti n g pr o gressi o n fr o m P A C S a n d P A C t o 
P A C G ( S u n 2 0 1 7 ). F urt her m ore, t he vast maj orit y of patie nts wit h A C G, wit h re p orts as hi g h 
as 9 4 t o 1 0 0 % i n b ot h Asia n a n d N ort h A merica n patie nts, re q uire a d diti o nal I O P c o ntr ol 
wit h t o pical me dicati o ns ( R os m a n 2 0 0 2). T he I O P is c o ntr olle d f or a p pr o xi matel y 4 0 % of 
P A C G patie nts o n a c o m bi nati o n of L PI a n d t o pical me dicati o ns, a n d t he re mai ni n g 
pr o p orti o n of patie nts re q uire a d diti o nal laser (e g,  A L PI) or i ncisi o nal s ur gical i nter ve nti o ns 
(e g, filteri n g s ur ger y) (R os ma n 2 0 0 2 ).  
T he m ost c o m m o nl y perf or me d filteri n g s ur ger y is tra bec ulect o m y. Alt h o u g h effecti ve, 
tra bec ulect o m y is a n i n vasi ve, res o urce-i nte nsi ve pr oce d ure t hat has bee n ass ociate d wit h 
hi g h rates of si g nifica nt p ost-s ur gical c o m plicat i o ns, treat me nt fail ure, a n d visi o n-t hreate ni n g 
a d verse effects, a n d a l o n g-ter m I O P c o ntr o l ma y still re q uire h y p ote nsi ve me dicati o ns 
p ost-s ur ger y ( C he n 2 0 0 9 ; S u n 2 0 1 7 ). Le ns e xtracti o n ma y als o be perf or me d i n c o m bi nati o n 
wit h a filteri n g pr oce d ure t o all o w f or a n gle- wi de ni n g a n d greater I O P-l o weri n g ( C he n 2 0 1 5 ; 
M urt h y 2 0 0 6 ; W a n g 2 0 1 2 ). Alt h o u g h p hac oe mulsificati o n a n d le ns e xtracti o n al o ne ca n be 
a n A C G treat me nt, c urre nt literat ure s u g gests c o m bi nati o n p hac otra bec ulect o m y a n d 
tra bec ulect o m y i n patie nts wit h P A C G ha ve si milar l o n g-ter m efficac y res ults at 1 t o 2 years, 
i ncl u di n g si milar I O P re d ucti o n, c o m plete s uccess rate, rate of f u ncti o ni n g ble bs, n u m ber of 
I O P-l o weri n g me dicati o ns, a n d s ur gical c o m plicati o ns (M urt h y 2 0 0 6 ; W a n g 2 0 1 2).  
G o ni os y nec hial ysis, w hic h ca n als o be perf or me d i n c o m bi nati o n wit h le ns e xtracti o n, mi g ht 
als o be use d as s ur gical treat me nt i n cases  wit h e xte nsi ve P A S t o stri p P A S fr o m t he 
tra bec ular s urface i n t he a n gle a n d i m pr o ve tra bec ular fl o w. Alt h o u g h it is effecti ve i n 
o pe ni n g a cl ose d a n gle a n d l o weri n g I O P w it h a n o verall s uccess rate of 8 0 % (Fa n g 2 0 1 0 ; 
Qi n g 2 0 1 2 ), it d oes n ot ha ve l o n g-ter m effecti ve ness a n d ma y be ass ociate d wit h 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 1 5 of 5 9 
 
 
c o m plicati o ns. Gla uc o ma drai na ge de vices (e g,  Baer vel dt i m pla nt, A h me d val ve) ma y be 
c o nsi dere d i n P A C G w he n me dicati o n a n d/ or tr a bec ulect o m y fail t o c o ntr ol I O P, b ut are als o 
ass ociate d wit h n u mer o us p ost o perati ve c o m plicati o ns ( Ge d de 2 0 1 2 ; Marc hi ni 2 0 1 5 ; 
Sa he b 2 0 1 4 ). U nli ke O A G treat me nt o pti o ns, t here are n o mi ni mall y i n vasi ve gla uc o ma 
s ur ger y o pti o ns a vaila ble f or A C G, d ue t o u ns uita ble de vice desi g ns, t o ser ve as a safer a n d 
less i n vasi ve alter nati ve t o be use d earlier i n t he treat me nt para di g m.  
X E N 4 5 Gla uc o ma Treat me nt S yste m (referre d t o as X E N), c o m prise d of t he X E N Gel 
I m pla nt (als o referre d t o as t he Gel I m pla nt) a n d t he X E N I nject or (als o referre d t o as t he 
I nject or) p ote ntiall y alle viates t his u n met nee d. A p pr o xi mat el y 6 m m l o n g a n d as wi de as a 
h u ma n hair,  t his s oft gelati n o us ste nt is i m pla nte d via a n a b i nter n o  s ur gical a p pr oac h 
t hr o u g h a s mall, self-seali n g c or neal i ncisi o n, t o facilitate a q ue o us h u m or drai na ge fr o m t he 
a nteri or c ha m ber t o t he s u bc o nj u ncti val s pace. T he gelati n i m parts h y dr o p hilic pr o perties t hat 
all o w t he Gel I m pla nt t o c o nf or m t o t he oc ular tiss ue b y e x pa n di n g w he n h y drate d u p o n 
c o ntact wit h t he a q ue o us h u m or. T his e x pa nsi o n mi g ht mi ni mize iss ues s uc h as mi grati o n, 
er osi o n, a n d c or neal e n d ot helial da ma ge o bser ve d i n ste nts wit h s y nt hetic materials.  
T he a b i nter n o  s ur gical a p pr oac h f or X E N is less i n vasi ve t ha n tra diti o nal gla uc o ma 
s ur geries a n d has se veral ot her a d va nta ges, i ncl u di n g mi ni mal tra u ma t o t he c o nj u ncti va, 
mai nte na nce of t he nat ural drai na ge pa t h wa ys, re d uce d scarri n g res p o nse, a n d t he a bilit y t o 
acc uratel y place t he de vice u n der direct vis ualiza ti o n of a nat o m y. Mi ni mi zi n g da ma ge t o t he 
c o nj u ncti va all o ws t he p ossi bilit y of f ut ure gla uc o ma s ur ger y.  
X E N is cleare d i n t he U nite d States f or t he ma na ge me nt of refract or y gla uc o mas, i ncl u di n g 
cases w he n pre vi o us s ur gical treat me nt has faile d, cases of pri mar y o pe n a n gle gla uc o ma 
( P O A G), a n d pse u d oe xf oliati ve or pi g me ntar y gla uc o ma wit h o pe n a n gles t hat are 
u nres p o nsi ve t o ma xi m u m t olerate d me dical t her a p y. X E N is a p pr o ve d i n m ulti ple c o u ntries 
w orl d wi de t o re d uce I O P i n patie nts wit h P O A G w he n pre vi o us me dical treat me nts ha ve 
faile d. 
X E N was pr os pecti vel y st u die d i n t he U nite d Stat es i n a m ultice nter, si n gle-ar m, o pe n-la bel, 
cli nical trial t o e val uate its safet y a n d effecti ve ness ( X E N P 1 3- 0 0 1 Cli nical St u d y Re p ort; 
Gr o ver 2 0 1 7 ). T his 1 2- m o nt h st u d y was c o n d ucte d i n patie nts wit h refract or y gla uc o ma 
w he n pre vi o us filteri n g or cili oa blati ve pr oce d ures faile d, or b y e x perie nce was k n o w n t o n ot 
pr o vi de satisfact or y res ults, or I O P was u nres p o n si ve t o ma xi mall y t olerate d me dicati o n. Of 
t he 6 5 s u bjects i m pla nte d (i nte nt-t o-treat p o p ulati o n), at baseline, 8 5 % of s u bjects ha d faile d 
pri or gla uc o ma pr oce d ures, 8 5 % were usi n g ≥ 3 h y p ote nsi ves, a n d mea n me dicate d I O P ( S D) 
was 2 5. 1 ( 3. 7) m m H g. At M o nt h 1 2, 7 6 % of s u bjects ac hie ve d ≥ 2 0 % I O P re d ucti o n fr o m 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 1 6 of 5 9 
 
 
baseli ne o n t he sa me or fe wer me dicati o ns; mea n I O P re d ucti o n ( S E M) was 6. 4 ( 1. 1) m m H g 
( 9 5 % CI: 4. 2, 8. 7). Mea n me dicati o n use ( S D) decrease d fr o m 3. 5 ( 1. 0) at baseli ne ( N = 6 5) 
t o 1. 7 ( 1. 5) at M o nt h 1 2 ( n = 5 2). At 1 2 m o nt hs, 1 3. 8 % of s u bjects re q uire d sec o n dar y 
s ur ger y. T here were n o i ntra o perati ve c o m plicati o ns. Oc ular a d verse e ve nts ( A Es) were 
m ostl y mil d t o m o derate res ol vi n g wit h o ut se q uelae; h y p ot o n y a n d nee dli n g pr oce d ures were 
m ost fre q ue ntl y re p orte d. Of t he 1 6 h y p ot o n y cases, 1 3 occ urre d o n Da y 1 a n d res ol ve d b y 
Da y 2 7; n o ne re q uire d s ur gical i nter ve nti o n. Of t he 2 1 s u bjects w h o re q uire d nee dli n g, 1 7 
e x perie nce d n o c o m plicati o ns. 
T he safet y a n d efficac y of X E N has als o bee n pre vi o usl y teste d i n a st u d y c o n d ucte d o utsi de 
t he U nite d States at t w o cli nical sites i n 2 3 e yes of 2 0 s u bjects ( mea n a ge, 6 4. 5 ± 1 4. 4 years) 
( R- 0 0 8 Cli nical St u d y Re p ort). T he maj orit y ( 16/ 2 0, 7 0 %) of s u bjects ha d a dia g n osis of 
P O A G, 4 s u bjects ( 1 3 %) ha d a dia g n osis of pi g m e ntar y gla uc o ma a n d 1 s u bject ( 4 %) ha d a 
dia g n osis of pse u d oe xf oliati ve gla uc o ma. At  baseli ne, t he mea n me dicate d I O P was 
2 4. 3 m m H g (ra n ge, 1 8. 0 - 4 2. 5 m m H g), a n d t he m ea n n u m ber of me dicati o ns of 2. 8 ( ± 1. 3) 
a n d t he me dia n at baseli ne bei n g 3. 0 me dicati o ns. T he 1 2- m o nt h res ults i n dicate d t hat X E N 
pr o vi des a safe mea ns t o re d uce I O P i n s u bjec ts wit h gla uc o ma. T he pri mar y effecti ve ness 
o utc o me (c ha n ge i n mea n I O P fr o m baseli ne t o  1 2 m o nt hs) i n dicate d t hat X E N l o were d I O P 
b y a mea n of 4 7 % w hile als o re d uci n g t he n u m ber of I O P-l o weri n g me dicati o ns b y a mea n of 
nearl y 2 me dicati o ns. I n a d d iti o n, t he mea n I O P at 1 2 m o nt hs was re d uce d t o 1 2. 1 m m H g 
fr o m a me di cate d baseli ne I O P of 2 4. 3 m m H g. T his st u d y f urt her s u p p orts t he safet y a n d 
effecti ve ness of X E N. 
F urt her m ore, retr os pecti ve case st u d y e x perie nce has de m o nstrate d its cli nical feasi bilit y i n 
patie nts wit h P A C G/ narr o w a n gles ( Milla n 2 0 1 7 ). T his st u d y was perf or me d o utsi de t he 
U nite d States i n 1 3 patie nts wit h P A C G. T he Gel I m pla nt (referre d t o as Gel Ste nt) was 
i m pla nte d i n 1 4 e yes ( 9 3. 3 %) i m me diatel y after cataract e xtracti o n, a n d i n 1 e ye ( 6. 7 %) as a 
sta n dal o ne pr oce d ure. At t he 1 2- m o nt h f oll o w-u p, t he mea n I O P decrease d fr o m 1 9. 5 m m H g 
at baseli ne ( n = 1 5) t o 1 3. 0 m m H g ( n = 8) . All e yes wit h a vaila ble data at M o nt h 1 2 
ac hie ve d ≥ 2 0 % I O P re d ucti o n ( mea n I O P re d ucti o n, −6. 5 m m H g). T he mea n n u m ber of 
me dicati o ns decrease d fr o m 3. 3 pre o perati vel y  t o 0. 9 ( 7 2 % decrease) at M o nt h 1 2. O ne 
patie nt was c o nsi dere d a n o n-res p o n der at M o nt h 1 2, re q uiri n g a n a d diti o nal gla uc o ma-
relate d s ur gical i nter ve nti o n. Tra nsie nt p osto perati ve h y p he ma ( micr osc o pic, 1 e ye; Gra de I, 
2 e yes) was t he m ost c o m m o n p ost o perati ve c o m plicati o n, f oll o we d b y c yst oi d mac ular 
e de ma ( 1 e ye, after c o m bi ne d s ur ger y). T hese res ults pr o vi de s u p p orti ve e vi de nce f or safet y 
a n d effecti ve ness of X E N i n patie nts wit h A C G/ narr o w a n gles. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 1 7 of 5 9 
 
 
T he c urre nt st u d y is a pr os pecti ve, m ultice nter, si n gle ar m, o pe n-la bel cli nical trial i n patie nts 
wit h A C G. A p pr o xi matel y 6 5 patie nts will be u nilaterall y i m pla nte d wit h X E N a n d f oll o we d 
f or 1 2 m o nt hs t o e val uate its safet y a n d effecti ve ness. 
T he s p o ns or will c o n d uct t his trial i n acc or da nce wit h all a p plica ble re g ulati o ns. 
2. 2  
Ris k a n d Be nefit 
Gla uc o ma is t he sec o n d lea di n g ca use of vis u al i m pair me nt a n d bli n d ness w orl d wi de. It 
res ults i n a s u bsta ntial ec o n o mic b ur de n f or patie nts, t heir fa milies, a n d s ociet y d ue t o 
sizea ble c osts of disease ma na ge me nt, visi o n l oss, a n d l ost pr o d ucti vit y. C urre nt treat me nt 
m o dalities f or A C G ha ve si g nifica nt li mitati o ns re gar di n g I O P-l o weri n g effecti ve ness, 
a dj u ncti ve me dicati o n use, re q uire me nt f or c o nc o mita nt cataract s ur ger y, c o m plicati o ns, a n d 
c ost. X E N pr o vi des effecti ve, mi ni mall y i n vasi ve, l o n g-lasti n g, safe, a n d d ura ble 
I O P-l o weri n g met h o d t hr o u g h s u bc o nj u ncti val drai na ge. Use of X E N i n patie nts wit h A C G 
mi g ht be ass ociate d wit h c o m plicati o ns relate d t o narr o w a n gle i ncl u di n g a q ue o us 
mis directi o n, cataract f or mati o n/ pr o gressi o n, c h or oi dal eff usi o n, c h or oi dal he m orr ha ge, 
c hr o nic iritis, c or neal e de ma, e n d ot helial t o uc h, flat a nteri or c ha m ber, h y p he ma ( > 1 wee k), 
Gel I m pla nt bl oc ka ge, iris atr o p h y, s hall o w a nteri or c ha m ber, a n d s u prac h or oi dal he m orr ha ge. 
T hese ris ks ca n be miti gate d wit h a p pr o priate c o nc o mita nt s ur gical pr oce d ures t hat wi de n t he 
a n gle (e g, cataract e xtracti o n, g o ni os y n ec hiael ysis, iri d o plast y). F urt her m ore, 
retr os pecti ve/case series data a vaila ble t o date o n narr o w a n d cl ose d a n gle patie nts s u g gest 
si milar safet y as i n patie nts wit h O A G. Ta ke n t o get her, t he be nefits o ut wei g h t he ris ks of 
X E N use i n A C G patie nts. 
2. 3  
Cli nic al R ati o n ale 
C o nsi deri n g t he i neffecti ve ness a n d c o m plicati o ns of t he a vaila ble s ur gical treat me nts f or 
c o ntr olli n g I O P i n A C G, X E N mi g ht offer a safe a n d effecti ve m o de of I O P-l o weri n g. 
3.  
St u d y O bjecti ves a n d Cli nic al H y p ot heses 
3. 1  
St u d y O bjecti ves 
T he p ur p ose of t he trial is t o e val uate t he safet y a n d I O P-l o weri n g effecti ve ness of X E N i n 
u p t o 6 5 patie nts wit h A C G.  

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 1 8 of 5 9 
 
 
3. 2  
Cli nic al H y p ot heses 
X E N will ha ve a n I O P-l o weri n g effect a n d a n acc e pta ble safet y pr ofile i n patie nts wit h A C G 
f oll o wi n g i m pla ntati o n. 
4.  
St u d y Desi g n 
4. 1  
Str uct ure 
T his is a pr os pecti ve, m ultice nter, si n gle-ar m, o pe n-la bel cli nical trial desi g ne d t o 
de m o nstrate t he safet y a n d I O P-l o weri n g effect i ve ness of X E N. F oll o wi n g c o m pleti o n of all 
re q uire d pre o perati ve e xa mi nati o ns, a n d if t he patie nt meets t he st u d y criteria, X E N will be 
u nilaterall y i m pla nte d. A p pr o xi matel y 6 5 patie nts will be e nr olle d at u p t o a p pr o xi matel y 
1 5 cli nical sites t o be u nilaterall y i m pla nte d wit h X E N a n d f oll o we d f or u p t o 1 2 m o nt hs 
p ost o perati vel y. 
4. 2  
D ur ati o n 
T he st u d y will s pa n a t otal of a p pr o xi matel y 1 4 m o nt hs i ncl u di n g a ma xi m u m of 2 m o nt hs 
bet wee n scree ni n g a n d baseli ne visits a n d f or u p t o 1 2 m o nt hs f or f oll o w- u p. 
4. 3  
Tre at me nt Gr o u ps a n d Tre at me nt Re gi me n 
4. 3. 1  
St u d y Tre at me nt 
X E N 4 5 Gla uc o ma Treat me nt S yste m, c o m prise d of t he X E N Gel I m pla nt a n d X E N I nject or. 
4. 3. 2  
Met h o ds f or M as ki n g 
N ot a p plica ble. 
4. 4  
Per missi ble a n d Pr o hi bite d Me dic ati o ns/ Tre at me nts 
4. 4. 1  
Per missi ble Me dic ati o ns/ Tre at me nts 
Use of c o nc o mita nt me dicati o ns ot her t ha n t he pr o hi bite d me dicati o ns ( Secti o n 4. 4. 2 ) is 
all o we d. T he use of a n y c o nc o mita nt me di cati o n or pr oce d ure, prescri pti o n or 
o ver-t he-c o u nter, is t o be rec or de d o n t he pati e nt’s electr o nic case re p ort f or m (e C R F) at eac h 
visit al o n g wit h t he reas o n t he me di cati o n is ta ke n. Pri or me dicati o ns will be rec or de d as part 
of t he me dical hist or y o n t he partici pa nt’s e C R F d uri n g t he first st u d y visit. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 1 9 of 5 9 
 
 
T hera p y c o nsi dere d necessar y f or t he patie nt’s welfare ma y be gi ve n at t he discreti o n of t he 
i n vesti gat or. If c o nc urre nt me dicati o ns may ha ve a n effect o n st u d y o utc o mes, t hese 
me dicati o ns m ust be a d mi nistere d i n d osa ges  t hat re mai n c o nsta nt t hr o u g h o ut t he e ntire 
d urati o n of t he st u d y. If t he per missi bilit y of a s pecific me dicati o n/treat me nt is i n q uesti o n, 
please c o ntact t he s p o ns or. 
Treat me nt of t he fell o w ( n o n-st u d y) e ye is n ot  restricte d, a n d fell ow e yes will recei ve 
a p pr o priate me dical a n d/ or s ur gical treat me nt, i ncl u di n g I O P-l o weri n g me dicati o ns, per t he 
i n vesti gat or’s discreti o n.  
Use of oc ular dec o n gesta nts or a nti hista mi nes is all o we d if n ot ta ke n wit hi n 2 da ys pri or t o a 
sc he d ule d visit. Oc ular dec o n gesta nts or a nti hista mi nes ma y be restarte d 3 da ys after 
i m pla ntati o n per t he i n vesti gat or’s discreti o n. 
S yste mic beta- bl oc ker c o ntai ni n g me dicati o ns are per mitte d, pr o vi de d t hat t he d ose/ d osi n g 
re gi me n has re mai ne d sta ble f or at least 2 m o nt hs pri or t o scree ni n g a n d is n ot a ntici pate d t o 
c ha n ge t hr o u g h o ut t he d urati o n of t he st u d y. 
T he use of s yste mic n o nster oi dal a ntii nfla m mat or y dr u gs is als o per mitte d. 
Pr oce d ures t o wi de n t he iri d oc or neal a n gle i n t he tar get q ua dra nt (e g, g o ni os y nec hial ysis, 
le ns e xtracti o n [clear le ns e xtracti o n or cataract s ur ger y/ p hac oe m ulsificati o n], a n d i ntra oc ular 
le ns [I O L] place me nt) are per mitte d o n t he o perati ve da y ( Da y 1) at t he i n vesti gat or’s 
discreti o n; h o we ver, all pr oce d ures m ust be s uccessf ul a n d u nc o m plicate d f or patie nts t o 
recei ve X E N. If t here are c o m plicati o ns t hat w o ul d be si g nifica nt e n o u g h t o i m pact t he st u d y 
res ults, t he patie nt will be e xite d fr o m t he stu d y. S uc h c o m plicati o ns i ncl u de, b ut are n ot 
li mite d t o, se vere c or neal b ur n, vitre o us rem o val/ vitrect o m y re q uire d, se vere a nteri or 
c ha m ber i nj uries, or c o m plicati o ns re q uiri n g t he place me nt of a n a nteri or c ha m ber le ns. 
Me dicati o ns a n d pr oce d ures re q uire d f or pre- o perati ve, o perati ve, a n d p ost o perati ve 
ma na ge me nt ( See Pr ot oc ol Pr oce d ure Ma n ua l), i ncl u di n g t he u nli kel y e ve nt t hat X E N 
re q uires re m o val f or si g nifica nt safet y reas o ns, are per mitte d at t he i n vesti gat or’s discreti o n.  
4. 4. 1. 1  
I O P-l o weri n g Me dic ati o ns  
S yste mic a n d t o pical (st u d y e ye o nl y) I O P-l o weri n g me dicati o ns, will be s us pe n de d o n t he 
da y of s ur ger y ( o perati ve da y [ Da y 1]); n o was h o ut peri o d is re q uire d. T he y ma y be 
i ntr o d uce d p ost o perati vel y t o ma na ge ele vate d I O P. At least o ne of t he f oll o wi n g criteria 
m ust be met t o i ntr o d uce I O P-l o we ri n g me dicati o ns p ost o perati vel y: 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 0 of 5 9 
 
 
•  I n vesti gat or deter mi nes I O P is n ot at tar get f or t he patie nt  
•  Pr o gressi o n of o ptic ner ve c u p pi n g ( vertical c u p-t o- disc rati o)  
•  Pr o gressi o n of vis ual fiel d l oss (c o nfir me d wit h a sec o n d vis ual fiel d test wit hi n o ne 
wee k).  
It is rec o m me n de d t hat t he me dicati o ns are prescri be d i n a ste p- wise fas hi o n b y i ntr o d uci n g 
o ne dr u g class at a ti me. Pri or t o c ha n gi n g t he first p ost o perati ve me dicati o n or a d di n g 
s u bse q ue nt me dicati o n(s), t he me dicati o n m ust be mai ntai ne d at a d osa ge a n d fre q ue nc y 
rec o m me n de d b y t he ma n ufact urer’s la beli n g f or a reas o na ble trial peri o d (e g, 1 wee k). 
I n vesti gat ors will c o nsi der a n y c o ntrai n dicati o ns t he patie nt ma y ha ve pre vi o usl y 
e x perie nce d (e g, aller gic reacti o n or lac k of efficac y) a n d/ or t he patie nt’s c urre nt cli nical 
sit uati o n. All c ha n ges t o t he I O P-l o weri n g me dicati o n re gi me n, t o pical a n d s yste mic, will be 
rec or de d o n t he a p pr o priate e C R F. 
T he i n vesti gat or ma y c o nsi der disc o nti n ui n g or l o weri n g t he d ose or fre q ue nc y of 
I O P-l o weri n g me dicati o ns w he ne ver it is i n t he i nterest of patie nt safet y, e g, cases of 
h y p ot o n y (I O P falls bel o w 6 m m H g). 
4. 4. 2  
Pr o hi bite d Me dic ati o ns/ Tre at me nts 
T he decisi o n t o a d mi nister a pr o hi bite d me dicat i o n/treat me nt is d o ne wit h t he safet y of t he 
st u d y patie nt as t he pri mar y c o nsi derati o n. T hera p y c o nsi dere d necessar y f or t he patie nt’s 
welfare ma y be gi ve n at t he discreti o n of t he i n vesti gat or. W he n p ossi ble, t he s p o ns or is t o be 
n otifie d bef ore t he pr o hi bite d me dicati o n/treat me nt is a d mi nistere d . 
T o pical a n d s yste mic I O P-l o weri n g m edicati o ns  m ust be s us pe n de d o n t he da y of s urger y 
( o perati ve da y [ Da y 1]); n o was h o ut peri o d is re q uire d. If re q uire d, I O P-l o weri n g 
m edicati o ns m ay be i ntr o d uce d p ost o perati ve l y t o m ana ge a n y ele vate d I OP  ( Secti o n 4. 4 . 1. 1).  
Use of c o ntact le ns i n t he st u d y e y e is pr o hi bite d d uri n g t he st u d y. 
T he f oll o wi n g me dicati o ns ( or classes of me di cati o ns) a n d treat me nt pr oce d ures are n ot 
per mitte d as c o nc urre nt t hera p y: 
•  S ur gical pr oce d ures n ot relate d t o  X E N a d mi nistrati o n a n d p ost o perati ve 
ma na ge me nt, i ncl u di n g ot her i ncisi o nal gla uc o ma treat me nts, s uc h as 
tra bec ulect o m y or gla uc o ma s h u nt i m pla ntati o n i n t he st u d y e ye, d uri n g t he 
st u d y peri o d 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 1 of 5 9 
 
 
•  Laser gla uc o ma treat me nts, s uc h as laser peri p heral iri d ot o m y a n d laser 
tra bec ul o plast y, i n t he st u d y e ye d uri n g t he st u d y peri o d 
•  S u bc o nj u ncti val, s u b- Te n o n’s, i ntra vitreal,  or ot her o p ht hal mi c i njecti o ns of 
a n y me dicati o ns i n t he st u d y e ye d uri n g t he st u d y peri o d, wit h t he e xce pti o n 
of a n y me dicati o ns re q uire d f or ble b ma na ge me nt ( Secti o n 6. 1. 3. 2. 2 ) 
•  Use of a n y n o nst u d y t o pical o p ht hal mic  me dicati o ns i n t he st u d y e ye, 
i ncl u di n g use of I O P-l o weri n g me dicati o ns wit h o ut meeti n g t he criteria 
s pecifie d i n Secti o n 4. 4. 1. 1 , d uri n g t he st u d y peri o d, wit h t he e xce pti o n of 
oc ular dec o n gesta nts or a nti hista mi nes ( Secti o n 4. 4. 1 ) 
•  Use of a n y o p ht hal mic (i ncl u di n g t o pical, i ntra vitreal, s u b- Te n o n’s, 
s u bc o nj u ncti val) c ortic oster oi ds i n eit her e ye fr o m 2 m o nt hs pri or t o t he 
baseli ne visit t hr o u g h st u d y e xit, e xce pt f o r use of pre o perati ve, o perati ve, a n d 
p ost o perati ve t o pical oc ular c ort ic oster oi ds relate d t o s ur ger y 
•  I nitiati o n of or alterati o ns i n oral, i ntra m usc ular, or i ntra ve n o us c ortic oster oi ds 
fr o m 2 m o nt hs pri or t o t he baseli ne visit t hr o u g h t he st u d y e xit 
•  Use of L A TI S S E ®  ( bi mat o pr ost f or h y p otric h osis) d uri n g t he st u d y peri o d i n 
t he st u d y e ye 
5.  
St u d y P o p ul ati o n 
5. 1  
N u m ber of P atie nts 
A p pr o xi mat el y 6 5 patie nts u nilaterall y i m pla nte d wit h X E N eit her as a sta n d-al o ne pr oce d ure 
or i n c o m bi nati o n wit h le ns e xtracti o n. A s u bs et of t his p o p ulati o n will i ncl u de a ma xi m u m of 
1 0 p ha kic patie nts (ie, will n ot u n der g o le ns e xtracti o n at ti me of X E N s ur ger y) a n d 1 0 
patie nts wit h a hist or y of tra bec ulect o m y or gla uc o ma s h u nt i m pla ntati o n, t o all o w f or a 
re prese ntati ve A C G patie nt p o p ulati o n i n t he st u dy. Si xt y-fi ve patie nts will be i m pla nte d t o 
e ns ure at least 5 0 e val ua ble patie nts wit h 1 2 m o nt hs of f oll o w- u p. Patie nts will be e nr olle d at 
a p pr o xi matel y 1 5 cli nical sites i n t h e Asia- Pacific a n d E ur o pea n re gi o ns.  
5. 2  
St u d y P o p ul ati o n C h ar acteristics 
A d ult patie nts wit h A C G wit h  u nc o ntr olle d I O P after ha vi n g faile d pre vi o us me dical a n d/ or 
s ur gical treat me nts will be i ncl u de d. If b ot h e yes q ualif y f or i ncl usi o n, t he n t he e ye wit h t he 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 2 of 5 9 
 
 
hi g her I O P at baseli ne will be t he st u d y e ye. If  b ot h e yes q ualif y f or i ncl usi o n a n d ha ve t he 
sa me baseli ne I O P, t he n t he ri g ht e ye will be t he st u d y e ye. Q ua lifie d patie nts will be 
u nilaterall y i m pla nte d wit h t he X E N eit her as a sta n d-al o ne pr oce d ure or i n c o m bi nati o n wit h 
le ns e xtracti o n. A s u bset of t his p o p ulati o n will i ncl u de a ma xi m u m of 1 0 p ha kic patie nts (ie, 
will n ot u n der g o le ns e xtracti o n at ti me of X E N s ur ger y) a n d 1 0 patie nts wit h a hist or y of 
tra bec ulect o m y or gla uc o ma s h u nt i m pla ntati o n, t o all o w f or a re prese ntati ve A C G patie nt 
p o p ulati o n i n t he st u d y.  
5. 3  
I ncl usi o n Criteri a 
T he f oll o wi n g are re q uire me nts f or e nr oll me nt i nt o t he st u d y: 
N o n- oc ul ar Criteri a f or I ncl usi o n 
1.  Male or fe male, ≥ 1 8 years of a ge a n d of le gal a ge of c o nse nt 
2.  Si g ne d writte n i nf or me d c o nse nt has bee n o btai ne d 
3.  A bilit y t o u n dersta n d a n d willi n g ness t o f o ll o w st u d y i nstr ucti o ns a n d is li kel y 
t o c o m plete all re q uire d visits a n d pr oce d ures 
Oc ul ar Criteri a f or I ncl usi o n  
4.  Dia g n osis of A C G defi ne d as areas of I T C prese nt i n ≥ 2 q ua dra nts a n d 
gla uc o mat o us da ma ge t o o ptic disc a n d vis ual fiel d, i n t he st u d y e ye.  
N ote: Pr oce d ures t o wi de n t he iri d oc or neal a n gle i n t he tar get q ua dra nt 
(e g, g o ni os y nec hial ysis, le ns e xtractio n [clear le ns e xtracti o n or cataract 
s ur ger y/ p hac oe m ulsificati o n], a n d I O L place me nt) are per mitte d o n t he 
o perati ve da y ( Da y 1) at t he i n vesti gat or’s discreti o n; h o we ver, all pr oce d ures 
m ust be s uccessf ul a n d u nc o m plicat e d f or patie nts t o recei ve X E N. A 
ma xi m u m of a p pr o xi matel y 1 0 p ha kic pa tie nts (ie, will n ot u n der g o le ns 
e xtracti o n at ti me of X E N s ur ger y) is all o we d i n t he st u d y. 
5.  I n t he o pi ni o n of t he i n vesti gat or, t he I O P is u nc o ntr olle d i n t he st u d y e ye 
after ha vi n g faile d pre vi o us me dical a n d/ or s ur gical treat me nt (e g, t o pical 
I O P-l o weri n g me dicati o ns, laser peri p heral iri d ot o m y, le ns e xtracti o n, 
gla uc o ma s h u nt i m pla ntati o n, tra bec ulect o m y) 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 3 of 5 9 
 
 
6.  I O P of ≥ 2 0 m m H g a n d ≤ 3 5 m m H g b y G ol d ma n n a p pla nati o n t o n o metr y i n 
t he st u d y e ye at scree ni n g a n d baseli ne ( H o ur 0) 
7.  St u d y e ye has healt h y, free, a n d m o bile  c o nj u ncti va i n t he tar get q ua dra nt 
8.  Gla uc o mat o us vis ual fiel d l oss wit h a mea n  de viati o n sc ore of at least - 1 d B i n 
t he st u d y e ye t hat, i n t he o pi ni o n of t he i n vesti gat or, is n ot f u ncti o nall y 
si g nifica nt (e g, s plit fi xati o n, fiel d defect wit hi n t he ce ntral 1 0 de grees t hat is 
vis uall y si g nifica nt or  li kel y t o ca use ce ntral vis ual i m pair me nt u p o n 
pr o gressi o n are e xcl u de d) 
5. 4  
E xcl usi o n Criteri a 
T he f oll o wi n g are criteria f or e xcl usi o n fr o m partici pati n g i n t he st u d y: 
N o n- oc ul ar Criteri a f or Excl usi o n 
1.  U nc o ntr olle d s yste mic disease (e g, dia betes, h y perte nsi o n) 
2.  Fe male patie nts w h o are pre g na nt, n u rsi n g, or pla n ni n g a pre g na nc y d uri n g 
t he st u d y, or w h o are of c hil d beari n g p ote ntial a n d n ot usi n g a relia ble mea ns 
of c o ntrace pti o n d uri n g t he st u d y. F or p ur p os es of t his st u d y, fe males will be 
c o nsi dere d of c hil d beari n g p ote ntial u n less t he y are nat urall y p ost me n o pa usal 
or per ma ne ntl y sterilize d (ie, t u bal occl usi o n, h ysterect o m y, bilateral 
sal pi n gect o m y, a n d/ or bilateral o o p h orect o m y). Nat ural me n o pa use is defi ne d 
as t he per ma ne nt cessati o n of me nstr ua l peri o ds, deter mi ne d retr os pecti vel y 
after a w o ma n has e x perie nce d 1 2 m o nt hs of a me n orr hea wit h o ut a n y ot her 
o b vi o us pat h ol o gical or  p h ysi ol o gical ca use 
3.  K n o w n or s us pecte d aller g y or se nsi ti vit y t o a n y me dicati o ns/ dia g n ostic 
a ge nts (e g, t o pical a nest hetic, dilati n g dr o ps, fl u orescei n) re q uire d f or t his 
pr ot oc ol or a n y of t he X E N c o m p o ne nts (e g, p orci ne pr o d ucts or 
gl utaral de h y de) 
4.  K n o w n hist or y of blee di n g dis or der or  pr ol o n ge d blee di n g after s ur ger y (i n 
t he o pi ni o n of t he i n vesti gat or) or t h ose o n p har mac ol o gic bl o o d t hi n ners 
ot her t ha n as piri n ( u p t o 1 0 0 m g/ da y)  
5.  C he m ot hera p y f or ca ncer treat me nt wit hi n 6 m o nt hs of scree ni n g 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 4 of 5 9 
 
 
6.  Hist or y of der mat ol o gic kel oi d f or mati o n 
7.  Partici pati o n i n a n ot her dr u g/ de vice/ o bser v ati o nal cli nical tria l c o nc urre ntl y or 
c o ncl u di n g wit hi n 3 0 da ys of scree ni n g  
8.  A n y c o n diti o n t hat w o ul d precl u de t he pa tie nt’s a bilit y t o c o m pl y wit h st u d y 
re q uire me nts, i ncl u di n g c o m pleti o n of t he st u d y 
9.  A n y c o n diti o n or a sit uati o n w hic h, i n t he i n vesti gat or's o pi ni o n, ma y p ut t he 
patie nt at si g nifica nt ris k, ma y c o nf o u n d t he st u d y res ults, or ma y i nterfere 
si g nifica ntl y wit h t he patie nt’s partici pati o n i n t he st u d y 
Oc ul ar Criteri a f or Excl usi o n 
1 0.  O pe n a n gle gla uc o ma, acti ve ac ute a n gl e cl os ure attac k, c o n ge nital gla uc o ma, 
j u ve nile gla uc o ma, sec o n dar y gla uc o mas (eg, a nteri or s u bl u xati o n of t he le ns, 
iris or ciliar y b o d y c ysts, acti ve iris an d a n gle ne o vasc ularizati o n, iri d oc or neal 
e n d ot helial s y n dr o me, a nteri or u ve itis, dr u g-i n d uce d) i n t he st u d y e ye 
1 1.  Hist or y of f oll o wi n g s ur geries i n t he st u d y e ye: 
a. i ncisi o nal refracti ve s ur ger y (e g, ra dial kerat ot o m y), ot her t ha n asti g matic 
kerat ot o m y or li m bal rela xi n g i ncisi o ns 
b.  c or neal graft i ncl u di n g partial grafts s uc h as Desce met’s stri p pi n g 
e n d ot helial kerat o plast y a n d De sce met’s me m bra ne e n d ot helial 
kerat o plast y  
c. pre vi o us laser or i ncisi o nal i ntra oc u lar s ur ger y t hat mi g ht i nterfere wit h 
t he o utc o me of t his trial 
H o we ver, pre vi o us i ncisi o nal a n d laser gla uc o ma s ur geries (e g, 
tra bec ulect o m y, gla uc o ma s h u nt i m pla ntati o n, laser tra bec ulo plast y, iri d ot o m y, 
cili oa blati ve pr oce d ures) or u nc o m plicate d p hac oe m ulsificati o n wit h I O L, 
occ urri n g m ore t ha n 3 m o nt hs pri or t o scree ni n g, are all o we d i n t he st u d y e ye. 
A ma xi m u m of 1 0 patie nts wit h a hist or y of tra bec ulect o m y or gla uc o ma 
s h u nt i m pla ntati o n (a wa y fr o m t he tar get q ua dra nt), is all o we d i n t his st u d y.  
1 2.  Pre vi o us gla uc o ma s h u nt i m pla ntati o n i n t he tar get q ua dra nt i n t he st u d y e ye 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 5 of 5 9 
 
 
1 3.  A ntici pate d nee d f or oc ular i ncisi o nal a n d/ or laser s ur ger y i n t he st u d y e ye 
d uri n g t he 1 2- m o nt h f oll o w- u p peri o d 
1 4.  A ntici pate d use of ot her t o pical oc ular me dicati o ns i n t he st u d y e ye e xce pt as 
descri be d i n Per missi ble Me dicati o ns/ Treat me nts ( Secti o n 4. 4. 1 ) 
1 5.  Oc ular (i n t he st u d y e ye) or s yste mic c ort ic oster oi d use wit hi n 3 0 da ys pri or t o 
scree ni n g (c o nti n ui n g c hr o nic s yste mic c ortic oster oi d use is all o we d) or 
k n o w n c ortic oster oi d res p o n der  
1 6.  Cli nicall y si g nifica nt i nfla m mati o n or i n fecti o n i n eit her e ye wit hi n 3 0 da ys 
pri or t o scree ni n g (e g, ble p haritis, c o nj u ncti vitis, keratitis, her pes si m ple x 
i nfecti o n)  
1 7.  Acti ve or hist or y of c hr o ni c u veitis i n t he st u d y e ye 
1 8.  C or neal or ot her oc ular a b n or malities (e g, b ull o us kerat o pat h y, kerat oc o n us) 
i n t he st u d y e ye t hat w o ul d precl u de acc urate rea di n gs wit h a n a p pla nati o n 
t o n o meter a n d/ or a c o ntact pac h y meter, or c o ul d c o nf o u n d st u d y res ults 
1 9.  Na n o p ht hal m os i n eit her e ye 
2 0.  Ce ntral c or neal t hic k ness ≤ 4 6 0 micr o ns or ≥ 6 2 0 micr o ns i n t he st u d y e ye 
2 1.  U na ble t o disc o nti n ue c o ntact le ns w ear i n t he st u d y e ye d uri n g t he st u d y  
2 2.  I m paire d e piscleral ve n o us drai na ge (eg, St ur ge- We ber or ot her e vi de nce of 
ele vate d ve n o us press ure) i n t he st u d y e ye 
2 3.  A p ha kia, a nteri or c ha m ber i ntra oc ular le ns, or pre vi o us c o m plicate d 
p hac oe m ulsificati o n s ur ger y i n t he st u d y e ye 
2 4.  Vitre o us prese nt i n t he a nteri or c ha m ber i n t he st u d y e ye 
2 5.  Prese nce of i ntra oc ular s ilic o ne oil i n t he st u d y e ye 
2 6.  Acti ve dia betic reti n o pat h y, c h or oi dal ne o vasc ularizati o n, bra nc h reti nal vei n 
occl usi o n, ce ntral reti nal vei n occl usi o n, pr oliferati ve reti n o pat h y, or ot her 
o p ht hal mic disease or dis or der i n t he st u d y e ye t hat c o ul d c o nf o u n d st u d y 
res ults 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 6 of 5 9 
 
 
2 7.  Vis uall y si g nifica nt cataract (ie, B C V A 2 0/ 4 0  S nelle n e q ui vale nt usi n g 
L o g Mar c hart at scree ni n g a n d baseli ne) i n t he st u d y e ye t hat will n ot be 
re m o ve d at t he ti me of X E N i m pla ntati o n  
2 8.  St u d y e ye wit h best-c orrecte d vis u al ac uit y ( B C V A) w orse t ha n 2 0/ 1 0 0 
( S nelle n e q ui vale nt usi n g L o g Mar c hart) at scree ni n g a n d baseli ne; fell o w 
( n o n-st u d y) e ye wit h B C V A w orse t ha n 2 0/ 2 0 0 at scree ni n g a n d baseli ne. A 
patie nt wit h a cataract i n t he st u d y e ye a n d B C V A w orse t ha n 2 0/ 1 0 0 i n t he 
st u d y e ye ma y be i ncl u de d if, i n t he o pi nio n of t he i n vesti gat or, t he patie nt is 
li kel y t o ha ve B C V A of 2 0/ 4 0 or better after cataract s ur ger y t hat will be 
perf or me d at t he ti me of X E N i m pla ntati o n. 
6.  
Pr oce d ures 
6. 1  
Pr oce d ures t o be Perf or me d 
E xa mi nati o n visits a n d visit wi n d o ws are pr o vi de d i n Ta ble 1- 1 . T he e xa mi nati o n 
re q uire me nts f or eac h visit are pr o vi de d i n t he f oll o wi n g pr ot oc ol secti o ns a n d i n Ta ble 1- 1 . 
It is rec o m me n de d t hat t he e xa mi nati o ns be c om plete d i n t he or der liste d, u nless ot her wise 
s pecifie d. 
Visits perf or me d bet wee n re p orti n g peri o ds will be d oc u me nte d o n a n u nsc he d ule d visit 
e C R F. T he i n vesti gat or will re p ort all fi n di n gs o btai ne d t o t he s p o ns or, i ncl u di n g I O P 
meas ure me nts, bi o micr osc o pic slit la m p a n d o p ht hal m osc o p y e xa mi nati o n fi n di n gs, 
c o nc o mita nt me dicati o ns, a n d A Es. 
6. 1. 1  
Scree ni n g Visit 
T he wi n d o w f or t his visit is u p t o 6 0 da ys pri o r t o s ur ger y. After o btai ni n g i nf or me d c o nse nt 
( Secti o n 1 0. 1. 2 ), t he foll o wi n g i nf or mati o n will be o btai ne d at t his visit: 
•  E val uati o n of i ncl usi o n/e xcl usi o n criteria 
•  Patie nt de m o gra p hics 
•  Me dical hist or y, s ur gical hist or y, o p ht h al mic hist or y, a n d o p ht hal mic s ur gical 
hist or y, i ncl u di n g prese nce of oc ular pat h ol o g y a n d c o nc o mita nt oc ular 
me dicati o ns ( b ot h e yes) 
•  Patie nt oc ular s y m pt o m q uesti o n naire  

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 7 of 5 9 
 
 
•  C o nc o mita nt me dicati o ns (s yste mic a n d o p ht hal mic) a n d pr oce d ures 
•  A Es 
•  Uri ne pre g na nc y test (f or fe ma les of c hil d beari n g p ote ntial) 
•  Ma nifest refracti o n ( b ot h e yes) 
•  B C V A usi n g L o g Mar c hart ( b ot h e yes) 
•  Vis ual fiel d testi n g ( b ot h e yes): M o n oc ular vis ual fiel d testi n g will be 
meas ure d usi n g t he H u m p hre y 2 4- 2 f ull t hres h ol d pr o gra m or S we dis h 
I nteracti ve T hres h ol di n g Al g orit h m ( SI T A) Sta n dar d a n d a relia ble, 
i nter preta ble vis ual fiel d will be o btai ne d f or patie nts wit h a pre o perati ve 
B C V A of better t ha n 2 0/ 1 0 0. T his assess m e nt is n ot re q uire d f or patie nts wit h 
B C V A of 2 0/ 1 0 0 or w orse. Vis ual fiel d res ults m ust be relia ble a n d 
i nter preta ble, or if u nrelia ble or u ni nter preta ble, t he vis ual fiel d test m ust be 
re peate d. A n u nrelia ble vis ual fiel d is defi ne d as vis ual fiel d meas ure me nts 
wit h > 3 3 % fi xati o n l osses, false p ositi ves, or false ne gati ves. Vis ual fiel d test 
perf or me d u p t o 6 m o nt hs pri or t o o perati ve da y ( Da y 1) is all o we d. 
•  Bi o micr osc o pic slit la m p e xa mi nati o n ( b ot h e yes): i ncl u des deter mi nati o n of 
o p ht hal mic me dical o bser vati o ns/c o m plica ti o ns, e val uati o n of t he c o n diti o n of 
t he e yeli ds, c o nj u ncti va, c or nea, a nteri or c ha m ber, iris/ p u pil, a n d le ns 
(t hr o u g h a dilate d p u pil). 
•  I O P ( H o ur 0 = 8: 0 0 a m ± 1 h o ur) meas ure me nt usi n g G ol d ma n n a p pla nati o n 
t o n o metr y ( b ot h e yes) usi n g t he 2-pers o n rea di n g met h o d ( See Pr ot oc ol 
Pr oce d ure Ma n ual); I O P m ust be c o m plete d pri or t o pac h y metr y, g o ni osc o p y, 
a n d o p ht hal m osc o p y. 
•  Pac h y metr y meas ure me nt of ce ntral c o r neal t hic k ness ( b ot h e yes) usi n g a n 
ultras o nic pac h y meter 
•  G o ni osc o p y ( b ot h e yes): i ncl u des assess m e nt of a n gle a b n or malities, s uc h as 
peri p heral a nteri or s y nec hiae, a n gle assess me nt of eac h q ua dra nt b y S haffer 
Gra de 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 8 of 5 9 
 
 
•  O p ht hal m osc o p y ( b ot h e yes): i ncl u des dilate d f u n d us e val uati o n a n d vertical 
c u p-t o- disc rati o. N o n- dilate d o p ht ha l m osc o p y ma y be perf or me d if t he 
i n vesti gat or belie ves t hat p u pil dilati o n ma y p ut t he patie nt at ris k. 
6. 1. 2  
B aseli ne Visit 
Baseli ne visit m ust be perf or me d 5 t o 7 da ys be f ore t he s ur ger y. T he f oll o wi n g tests m ust be 
perf or me d o n t he baseli ne visit pri or t o t he i nit iati o n of pre o perati ve c ortic oster oi d treat me nt:  
•  E val uati o n of i ncl usi o n/e xcl usi o n criteria 
•  Me dical hist or y, s ur gical hist or y, o p ht h al mic hist or y, a n d o p ht hal mic s ur gical 
hist or y, i ncl u di n g prese nce of oc ular pat h ol o g y a n d c o nc o mita nt oc ular 
me dicati o ns ( b ot h e yes) 
•  C o nc o mita nt me dicati o ns (s yste mic a n d o p ht hal mic [ b ot h e yes]) a n d 
pr oce d ures 
•  A Es 
•  Uri ne pre g na nc y test (f or fe ma les of c hil d beari n g p ote ntial) 
•  Ma nifest refracti o n ( b ot h e yes) 
•  B C V A usi n g L o g Mar c hart ( b ot h e yes) 
•  Bi o micr osc o pic slit la m p e xa mi nati o n ( b ot h e yes) 
•  Di ur nal I O P meas ure me nt ( b ot h e yes): T hree I O P meas ure me nts ta ke n o ver a n 
8- h o ur peri o d o n t he sa me da y a p pr o xi m atel y 4 h o urs a part, at H o ur 0 ( ± 1 
h o ur), H o ur 4 = H o ur 0 + 4 h o urs ( ± 3 0 mi n utes), a n d H o ur 8 = H o ur 0 + 8 
h o urs ( ± 3 0 mi n utes). As sc he d uli n g per mits, t he patie nt m ust ha ve 
a p pr o xi matel y t he sa me H o ur 0 ti me of da y t hr o u g h o ut t he st u d y. I O P m ust be 
c o m plete d pri or t o o p ht hal m osc o p y. 
•  O p ht hal m osc o p y ( b ot h e yes) 
6. 1. 2. 1  
Pre o per ati ve Me dic ati o ns 
At t he baseli ne visit, patie nts will be prescri be d a n d i nstr ucte d t o self-a d mi nister t he 
f oll o wi n g pre o perati ve medicati o ns i n T able 6 – 1  ( See Pr ot oc ol Pr oce d ure Ma n ual). If 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 2 9 of 5 9 
 
 
me dicati o ns i n T able 6 – 1  are n ot all owe d as per l ocal la ws a n d/ or re g ulati o ns , i n vesti gat or’s 
sta n dar d practice ma y be s u bstit ute d base d o n pri or disc ussi o ns wit h t he s p o ns or. All 
pre o perati ve me dicati o ns will be rec or de d i n t he e C R F. 
Ta ble 6 – 1  
Pre o per ati ve Me dic ati o ns   
Me dic ati o n 
D ose 
D ur ati o n 
T o pical br oa d s pectr u m o p ht hal mic a nti bi otic, 
rec o m me n de d wit h o ut preser vati ve ( See Pr ot oc ol 
Pr oce d ure Ma n ual) 
QI D  
O ne da y pri or t o s ur ger y  
T o pical c ortic oster oi d: difl u pre d nate 0. 0 5 % or 
pre d nis ol o ne acetate 1 % or e q ui vale nt ( See Pr ot oc ol 
Pr oce d ure Ma n ual)  
QI D  
5 t o 7 da ys pri or t o s ur ger y, per 
i n vesti gat or’s discreti o n 
 
QI D = 4 ti mes dail y 
Patie nts m ust be i nstr ucte d t o disc o nti n ue al l t o pical a n d s yste mic I O P-l o weri n g me dicati o ns 
o n t he da y of s ur ger y.  
6. 1. 3  
O per ati ve Visit ( D a y 1) 
Patie nts m ust be sc he d ule d f or s ur ger y w it hi n 6 0 da ys of scree ni n g. T he f oll o wi n g 
pr oce d ures m ust be perf or me d pri or t o  t he i m pla ntati o n of st u d y treat me nt: 
•  E val uati o n of i ncl usi o n/e xcl usi o n criteria 
•  Me dical hist or y, s ur gical hist or y, o p ht h al mic hist or y, a n d o p ht hal mic s ur gical 
hist or y, i ncl u di n g prese nce of oc ular pat h ol o g y a n d c o nc o mita nt oc ular 
me dicati o ns ( b ot h e yes) 
•  C o nc o mita nt me dicati o ns (s yste mic a n d o p ht hal mic [ b ot h e yes]) a n d 
pr oce d ures 
•  A Es 
•  Uri ne pre g na nc y test (f or fe ma les of c hil d beari n g p ote ntial) 
T he i m pla ntati o n pr oce d ure m ust be perf or me d i n  a n a p pr o ve d s ur gical s uite or o perati n g 
r o o m usi n g sta n dar d ase ptic tec h ni q ue a n d sta n dar d o p ht hal mic s ur gical tec h ni q ues t o 
pre pare t he patie nt a n d t he o perati ve st u d y e y e. Pre o perati ve a n d i n tra o perati ve s ur gical 
me dicati o ns will be a d mi nistere d as c ust o mar y f or t he i n vesti gat or. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 0 of 5 9 
 
 
It is rec o m me n de d t hat t he tar get q ua dra nt be t he s u peri or nasal q ua dra nt, u nless c o nj u ncti val 
scarri n g will i n hi bit ble b f or mati o n. If i m pla ntati o n is n ot p ossi ble i n t his q ua dra nt, t he or der 
of prefere nce f or Gel I m pla nt l ocati o n is s u peri or te m p oral, i nferi or nasal, a n d lastl y i nferi or 
te m p oral. 
A detaile d descri pti o n of t he X E N s ur gical pr oc e d ure is pr o vi de d i n t he Pr ot oc ol Pr oce d ure 
Ma n ual. T he ge neral ste ps of t he s u r gical pr oce d ure are as f oll o ws: 
1.  Sta n dar d o p ht hal mic s ur ger y tec h ni q ues m ust be use d t o pre pare t he patie nt 
a n d t he e ye. T he tar get area m ust be pretreate d wit h mit o m yci n C (see 
Pr ot oc ol Pr oce d ure Ma n ual f or d osi n g a n d i ntra o perati ve a p plicati o n details). 
2.  S ur ge o ns ma y use t heir sta n dar d of care t o o btai n access t o t he s ur gical 
q ua dra nt. T he nee dle of t he sterile X E N I nject or prel oa de d wit h t he X E N Gel 
I m pla nt is a d va nce d t hr o u g h t he perip heral c or nea a n d acr oss t he a nteri or 
c ha m ber (ie, a b i nter n o ) t o war d t he tar gete d q ua dra nt. C or neal e ntr y will be at 
least 1 t o 2 m m a nteri or t o t he li m b us (ie, n ot at t he li m b us or be hi n d it) t o 
e ns ure pr o per a n g ulati o n o n t he Gel I m pla nt u p a n d a wa y fr o m t he iris. T he 
Gel I m pla nt will be place d t hr o u g h t he ce nter of t he a n gle. 
3.  O nce t he nee dle is ali g ne d wit h t he desi re d e ntr y p oi nt i n t he a nteri or c ha m ber 
a n gle, t he s ur ge o n a d va nces t he nee dle  i n t he a nteri or c ha m ber a n gle a n d 
sclera u ntil t he s ur ge o n is a ble t o vis ualize t he nee dle be vel as it e xits t he 
sclera i nt o t he s u bc o nj u ncti val s pace. 
4.  T he s ur ge o n i nitiates release of t he X E N Gel I m pla nt b y m o vi n g t he sli der of 
t he X E N I nject or. To de pl o y t he Gel I m pla nt, a f or war d m o ve me nt of t he bl ue 
sli der at t he ce nter of t he I nject or deli vers t he Gel I m pla nt a n d retracts t he 
nee dle. T he sli der will st o p at t he e n d of its tra vel i n dicati n g t hat t he 
pr oce d ure is c o m plete. 
Fi g ure 6 – 1  pr o vi des dia gra ms of t he ste ps re q uire d t o c o m plete t he i m pla ntati o n pr oce d ure. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 1 of 5 9 
 
 
Fi g ure 6 – 1  
X E N I m pl a nt ati o n Pr oce d ure 
 
a.   T he s ur ge o n a d va nces t he nee dle t hr o u g h t he 
tra bec ular mes h w or k a n d t he sclera u ntil t he 
nee dle be vel ca n be vis ualize d i n t he 
s u bc o nj u ncti val s pace. 
b.   O nce t he nee dle is pr o perl y p ositi o ne d, 
t he Gel I m pla nt ca n be release d fr o m t he 
nee dle b y t he s ur ge o n.  
F oll o wi n g s ur ger y, a pr otecti ve s hiel d or glasse s will be a p plie d o ver t he o perati ve e ye. T he 
patie nt will be i nstr ucte d t o kee p t he s hiel d or glasses o ver t he o perati ve e ye u ntil t he first 
f oll o w- u p visit a n d t he n, at bedti me, f or at least a wee k. 
6. 1. 3. 1  
P ost o per ati ve Me dic ati o ns 
T he i n vesti gat or will prescri b e a n d i nstr uct t he patie nt t o self-a d mi nister t he p ost o perati ve 
me dicati o ns liste d i n Ta ble 6 – 2  ( See Pr ot oc ol Pr oce d ure Ma n ual). I n vesti gat or discreti o n 
ma y be use d t o a dj ust t he bel o w p ost o perati ve  me dicati o n re gi me n, if re q uire d. All c ha n ges 
i n t he p ost o perati ve re gi me n will be d oc u me nte d o n t he a p pr o priate e C R F. 
Ta ble 6 – 2  
P ost o per ati ve Me dic ati o ns   
Me dic ati o n 
D ose 
D ur ati o n 
T o pical br oa d s pectr u m o p ht hal mic a nti bi otic, 
rec o m me n de d wit h o ut preser vati ve ( See Pr ot oc ol 
Pr oce d ure Ma n ual)   
QI D  
Wee k 1 f oll o wi n g s ur ger y  
T o pical c ortic oster oi d: difl u pre d nate 0. 0 5 % or 
pre d nis ol o ne acetate 1 % or e q ui vale nt ( See Pr ot oc ol 
Pr oce d ure Ma n ual)   
QI D  
TI D  
BI D  
Q D  
Wee ks 1- 4 f oll o wi n g s ur ger y  
Wee k 5 f oll o wi n g s ur ger y  
Wee k 6 f oll o wi n g s ur ger y  
Wee ks 7- 1 2 f oll o wi n g s ur ger y  
QI D = 4 ti mes dail y; TI D = 3 ti mes dail y; BI D = t wice dail y; Q D = o nce dail y 
6. 1. 3. 2  
P ost o per ati ve M a n a ge me nt 
6. 1. 3. 2. 1  
H y p ot o n y 
I n vesti gat ors m ust m o nit or patie nts f or cli nicall y si g nifica nt fi n di n gs relate d t o h y p ot o n y, 
s uc h as s hall o w a nteri or c ha m ber, persiste nt c h or oi dal eff usi o ns, h y p ot o n y mac ul o pat h y, a n d 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 2 of 5 9 
 
 
visi o n l oss. I n vesti gat ors will use t heir best me dical j u d g me nt t o ma na ge h y p ot o n y, i ncl u di n g 
ref or mati o n of t he a nteri or c ha m ber. C ycl o ple gic me dicati o ns ma y be use d f or patie nts, as 
nee de d, d uri n g t he i nitial heali n g p hase or i n  p ha kic e yes. If use d, me dicati o ns m ust be 
rec or de d o n t he e C R F.  
6. 1. 3. 2. 2  
Ble b M a n a ge me nt 
A fi br otic res p o nse ma y occ ur i n st u d y patie nt s as a f u ncti o n of pre vi o us s ur geries a n d 
me dicati o n use. I n vesti gat ors will m o nit or pa tie nts f or mai nte na nce of a f u ncti o nal ble b. 
I n vesti gat ors will use sta n dar d of care c ust o mar y f or ble b nee dli n g. A nti-fi br otic a ge nts 
(e g, mit o m yci n C) ca n be use d d uri n g nee dli n g as per i n vesti gat or’s discreti o n. 
To all o w X E N t o c o nti n ue t o pr o vi de a c o n d u it f or a q ue o us fl o w i nt o t he s u bc o nj u ncti val 
s pace, nee dli n g ma y be perf or me d t o mec ha nicall y re m o ve tiss ue a d hesi o ns bet wee n t he 
sclera a n d t he c o nj u ncti va. 
I n a d diti o n t o ha vi n g I O P a b o ve tar get le vel, at least o ne of t he f oll o wi n g criteria m ust be met 
pri or t o perf or mi n g a nee dli n g pr oce d ure: 
•  Flat ble b w here filtrati o n area is fi br otic or bl oc ke d 
•  Patie nt has a hi g h ris k of ble b fail ure, base d o n assess me nt b y t he i n vesti gat or  
T he i n vesti gat or will c o nsi der t he patie nt’s c urre nt cli nical sit uati o n as t he basis f or 
perf or mi n g a nee dli n g pr oce d ure. A s mall ga u ge nee dle (e g, 2 7 G or less) is rec o m me n de d, 
wit h e ntr y i nt o c o nj u ncti va a fe w milli meters a wa y fr o m t he ble b/i m pla nt e xit area. A d va nce 
t he nee dle caref ull y t o war ds t he i m pla nt e xit a n d brea k a n y tiss ue a d hesi o ns a n d fi br otic 
tiss ue ar o u n d t he i m pla nt e xit site. See Pr ot ocol Pr oce d ure Ma n ual f or f urt her details. 
6. 1. 3. 2. 3  
De vice E x pl a nt 
X E N ma y be re m o ve d if t he i n vesti gat or belie ves t hat it is i n t he best i nterest of t he patie nt. 
De vice re m o val ma y be c o nsi dere d i n t he f oll o wi n g sit uati o ns: 
•  Persiste nt h y p ot o n y t hat ca n n ot be miti gate d b y ot her mea ns (see 
Secti o n 6. 1. 3. 2. 1 ) 
•  U veitis, gla uc o ma a n d h y p he ma s y n dr o me  
•  Gr oss de vice mal p ositi o n 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 3 of 5 9 
 
 
•  S ur gical pr oce d ure t hat re q uires e x pla nt (e g, tra bec ulect o m y) 
I n vesti gat ors will ma ke all eff orts t o n otif y t he s p o ns or pri or t o e x pla ntati o n of t he de vice. 
F or e x pla ntati o n of X E N, t he f oll o wi n g will be c o nsi dere d: 
•  I m pla nt re m o val t hr o u g h t he c o nj u ncti va: 
A s mall ( 1 t o 2 m m) c o nj u ncti val i ncisi o n is ma de near t he distal e n d of t he 
i m pla nt. Usi n g f orce ps, sl o wl y re m o ve t he i m pla nt o ut of t he e ye. 
I n vesti gat or’s discreti o n will be use d t o cl ose t he c o nj u ncti val w o u n d. 
•  I m pla nt re m o val fr o m t he a nteri or c ha m ber: 
A s mall ( 1 t o 2 m m) i ncisi o n is create d t o e nter t he a nteri or c ha m ber. After 
usi n g a p pr o priate met h o ds t o mai ntai n t he a nteri or c ha m ber s ha pe (e g, 
i njecti o n of visc oelastic), f orce ps ca n be use d t o re m o ve t he i m pla nt fr o m t he 
e ye. I n vesti gat or’s discreti o n will be use d i n t he met h o d f or cl os ure of t he 
c or neal i ncisi o n.  
All de vice e x pla nts will be c o nsi dere d de vice fail ures. Patie nts w h o ha ve t heir de vices 
re m o ve d will be wit h dra w n fr o m t he st u d y. T hese patie nts will be f oll o we d u ntil t he patie nt 
is dee me d sta ble b y t he i n vesti gat or. E xa mi nati ons ma y be perf or me d as necessar y t o e ns ure 
t he safet y a n d well bei n g of patients d uri n g t he st u d y peri o d.  
6. 1. 4  
F oll o w- u p E x a mi n ati o ns a n d Cli nic al P ar a meters 
T he p ost o perati ve f oll o w- u p d urati o n will be 1 2 m o nt hs. 
Patie nts will u n der g o p ost o perati ve visi ts acc or di n g t o t he visit sc hed ule i n T a ble 1- 1. 
T he f oll o wi n g i nf or mati o n will be o btai ne d f or t he st u d y e ye at t he p ost o perati ve visits, 
alt h o u g h n ot all are re q uire d at eac h visit: 
•  Patie nt oc ular s y m pt o m q uesti o n naire 
•  C o nc o mita nt me dicati o ns ( o p ht hal mi c a n d s yste mic) a n d pr oce d ures 
•  C ha n ges i n healt h t hat ma y i nfl ue nce t he st u d y o utc o mes 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 4 of 5 9 
 
 
•  A Es 
•  Ma nifest refracti o n, o btai ne d f or B C V A te sti n g: t o be c o m plete d at sc he d ule d 
visits. I n a d diti o n, ma nifest refracti o n will be perf or me d d uri n g a n y visit if 
best-c orrecte d vis ual ac uit y ( B C V A) re d ucti o n of ≥ 2 li nes is o bser ve d si nce 
t he last B C V A e xa mi nati o n.  
•  B C V A usi n g L o g Mar c hart 
•  Bi o micr osc o pic slit la m p e xa mi nati o n, i ncl u di n g assess me nt f or Gel I m pla nt 
place me nt a n d ble b c haracteristics 
•  I O P meas ure me nt ( H o ur 0 ± 1 h o ur) usin g G ol d ma n n a p pla nati o n t o n o metr y; 
I O P m ust be c o m plete d pri or t o pac h y metr y, g o ni osc o p y, a n d o p ht hal m osc o p y.  
•  Pac h y metr y meas ure me nts of ce ntral c or neal t hic k ness usi n g a n ultras o nic 
pac h y meter 
•  G o ni osc o p y 
•  O p ht hal m osc o p y 
6. 1. 5  
1 2- M o nt h P ost o per ati ve Visit/ E arl y E xit Visit 
Patie nts will be e xite d fr o m t he st u d y o nce t he y ha ve c o m plete d t he 1 2- m o nt h visit. 
T he f oll o wi n g i nf or mati o n will be o btai ne d f or t he st u d y e ye: 
•  Patie nt oc ular s y m pt o m q uesti o n naire 
•  C o nc o mita nt me dicati o ns ( o p ht hal mi c a n d s yste mic) a n d pr oce d ures 
•  A Es 
•  Uri ne pre g na nc y test (f or fe ma les of c hil d beari n g p ote ntial) 
•  Ma nifest refracti o n 
•  B C V A usi n g L o g Mar c hart 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 5 of 5 9 
 
 
•  Vis ual fiel d testi n g: If t he vis ual fiel d assess me nt at t his visit s h o ws 
pr o gressi o n of vis ual fiel d l oss fr o m ba seli ne ( defi ne d as a w orse ni n g of at 
least 3 d B i n mea n de viati o n sc ore), a sec o n d vis ual fiel d test m ust be 
perf or me d wit hi n o ne wee k t o c o nfir m t he pr o gressi o n. If t he sec o n d vis ual 
fiel d test is n ot c o nfir mat or y or is e q ui v ocal, a t hird test m ust be perf or me d 
wit hi n a wee k t o c o nfir m res ults.  
•  Bi o micr osc o pic slit la m p e xa mi nati o n, i ncl u di n g assess me nt f or Gel I m pla nt 
place me nt a n d ble b c haracteristics  
•  Di ur nal I O P usi n g G ol d ma n n A p pla nati o n To n o metr y; I O P m ust be c o m plete d 
pri or t o pac h y metr y, g o ni osc o p y, a n d o p ht hal m osc o p y. 
•  Pac h y metr y meas ure me nts of ce ntral c or neal t hic k ness usi n g a n ultras o nic 
pac h y meter 
•  G o ni osc o p y  
•  O p ht hal m osc o p y 
6. 2  
I nstr ucti o ns f or t he P atie nts 
Patie nts will be i nstr ucte d t o strictl y f oll o w t he st u d y visit sc he d ule, a d here t o pre- a n d p ost-
o perati ve me dicati o n i nstr ucti o ns ( Secti o ns 6. 1. 2. 1  a n d 6. 1. 3. 1 ), a n d t o re p ort all c ha n ges i n 
t heir c o n diti o n t o t he i n vesti gati ve site. 
I nstr ucti o ns will be gi ve n t o t he patie nt t o mai ntai n a sta ble d ose of a n y c o nc o mita nt 
me dicati o n use d c hr o nicall y, or a n y ne w me di cati o ns i nitiate d d uri n g t he st u d y w he ne ver 
p ossi ble. Patie nts will be i nstr ucte d t o c o m m u nicate a n y c ha n ges t o t heir me dicati o n at t heir 
ne xt st u d y visit. Patie nts will als o be re mi n de d t o c o ntact t he st u d y site if t he y are 
e x perie nci n g a n y diffic ulties d uri n g t heir st u d y partici pati o n. 
6. 3  
U nsc he d ule d Visits 
A d diti o nal e xa mi nati o ns ma y be perf or me d as n ecessar y t o e ns ure t he safet y a n d well bei n g 
of patie nts d uri n g t he st u d y peri o d. U nsc he d ule d  visit e C R Fs m ust be c o m plete d f or eac h 
u nsc he d ule d visit. A n assess me nt of a n y A E m ust be c o m plete d.  

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 6 of 5 9 
 
 
6. 4  
E arl y Disc o nti n u ati o n of P atie nts 
Eac h patie nt reser ves t he ri g ht t o wit h dra w fr o m t he st u d y at a n y ti me wit h o ut je o par d y t o 
his/ her f ut ure me dical care. I n a d diti o n, pa tie nts meeti n g wit h dra wal criteria ( Secti o n 6. 5 ) 
will be disc o nti n ue d fr o m t he st u d y. All f oll o w- u p assess me nts a n d pr oce d ures are t o be 
perf or me d at t he fi nal st u d y visit. Patie nts ma y als o be a d mi nistrati vel y wit h dra w n if t he y d o 
n ot ret ur n f or f oll o w- u p visits.  
F or a n y patie nt w h o wit h dra ws fr o m t he st u d y, t he date a n d reas o n f or wit h dra wal will be 
rec or de d o n t he e C R F. If a n A E is o n g oi n g at t he ti me of wit h dra wal, t he i n vesti gat or will 
atte m pt t o f oll o w t he patie nt u ntil t he A E has bee n res ol ve d or f oll o w- u p is n o l o n ger 
p ossi ble. T he i n vesti gat or s hall as k f or t he patie nt’s per missi o n t o f oll o w his/ her 
stat us/c o n diti o n o utsi de t he st u d y. 
If a patie nt fails t o ret ur n f or o ne or m ore sche d ule d st u d y visits, t he i n vesti gat or will atte m pt 
t o c o ntact t he patie nt t o deter mi ne a n d d oc u me nt t he reas o n t he patie nt has faile d t o ret ur n 
a n d t o e nc o ura ge c o m plia nce w it h t he st u d y visit sc he d ule. 
N otificati o n of earl y patie nt disc o nti n uati o n fr o m t he st u d y a n d t he reas o n f or disc o nti n uati o n 
will be ma de t o t he s p o ns or a n d clearl y d oc u me nte d o n t he a p pr o priate e C R F. 
W he n a patie nt disc o nti n ues or wit h dra ws fr o m t he st u d y bef ore 1 2 m o nt hs, e ver y eff ort 
s h o ul d be ma de t o ha ve t hese patie nts ret ur n t o t he cli nical ce nter t o c o m plete t he pr oce d ures 
f or t he earl y e xit visit. 
6. 5  
Wit h dr a w al Criteri a 
Patie nts ma y v ol u ntaril y wit h dra w fr o m t he st u d y at a n y ti me. 
Patie nts w h o ha ve t heir de vices re m o ve d or ha ve a s ut ure place d t o cl ose t he scleral c ha n nel, 
will be wit h dra w n fr o m t he st u d y. 
Patie nts w h o are n ot i m pla nte d wit h X E N d uri n g s ur ger y will be wit h dra w n fr o m t he st u d y 
a n d c o nsi dere d a scree n fail ure. I n vesti gat ors are rec o m me n de d t o f oll o w t he patie nt u ntil 
t he y are sta ble. 
T he i n vesti gat or will c o nsi der wit h dra wi n g a patie nt fr o m t he st u d y earl y if a n y of t he 
f oll o wi n g criteria are met: 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 7 of 5 9 
 
 
•  Patie nt de vel o ps ( or has a n e xacer bati o n of) a me dical c o n diti o n t hat, i n t he 
o pi ni o n of t he i n vesti gat or, c o m pr o mises t h e patie nt’s a bilit y t o partici pate i n 
t he st u d y 
•  Patie nt is u n willi n g or u na ble t o c o nti n ue t o c o m pl y wit h st u d y pr oce d ures 
•  Patie nt is u n willi n g or u na ble t o c o nti n ue i n t he st u d y 
W he ne ver p ossi ble, t he decisi o n t o wit h dra w a patie nt fr o m t he st u d y or st u d y treat me nt will 
be disc usse d wit h t he s p o ns or. 
7.  
Res p o nse Me as ures a n d S u m m ar y  of D at a C ollecti o n Met h o ds 
Detaile d i nf or mati o n o n e q ui p me nt a n d met h o d ol o g y t o  be use d is pr o vi de d i n t he Pr ot oc ol 
Pr oce d ure Ma n ual.  
7. 1  
Effecti ve ness Me as ures 
Pri mar y effecti ve ness meas ures will be assesse d  at all visits acc or di n g t o t he sc he d ule i n 
T a ble 1- 1. 
T he pri mar y effecti ve ness meas ure, I O P, will be meas ure d usi n g a G ol d ma n n a p pla nati o n 
t o n o meter. E xa mi ners m ust perf or m all effecti ve ness I O P meas ure me nts at a p pr o xi matel y t he 
sa me ti me of da y f or a gi ve n patie nt t hr o u g h o ut t he st u d y w he ne ver p ossi ble. I O P m ust be 
c o m plete d pri or t o pac h y metr y, g o ni osc o p y, a n d o p ht hal m osc o p y. 
T he n u m ber of c o nc o mita nt I O P-l o weri n g me dicati o ns f oll o wi n g i m pla ntati o n will als o be 
rec or de d. 
7. 2  
S afet y Me as ures 
T he f oll o wi n g will be c ollecte d a n d rec or de d o n t he a p pr o priate e C R F pa ge(s): 
•  A Es: All A Es, fr o m t he m o me nt t he patie nt si g ns t he I nf or me d C o nse nt F or m, 
will be m o nit ore d a n d rec or de d i n t he patie nt’s s o urce d oc u me nts. All e ve nts 
will be re p orte d t o t he s p o ns or o n a n A E e C R F, i ncl u di n g seri o us ness, se verit y, 
acti o n ta ke n a n d relati o ns hi p t o st u d y treat me nt. If A Es occ ur, t he first 
c o ncer n will be t he safet y of t he st u d y patie nt. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 8 of 5 9 
 
 
•  Fe males of c hil d beari n g p ote ntial will  ha ve pre g na nc y tests perf or me d. 
Pre g na nc y test kits will be pr o vi de d b y t he site a n d will be a d mi nistere d 
acc or di n g t o t he i nstr ucti o ns  pr o vi de d wit h t he tests. 
Me as ures of oc ul ar s afety i ncl u de: 
Vis u al ac uit y : Vis ual ac uit y tests will be perf or me d at all sc he d ule d visits, as descri be d i n 
T a ble 1- 1. Ma nifest refracti o n usi n g S nelle n e q ui vale nt wit h a l o g Mar c hart (see Pr ot oc ol 
Pr oce d ure Ma n ual) will be perf or me d at Scree ni n g, Baseli ne, M o nt h 3, a n d M o nt h 1 2/ E xit. 
At all ot her visits, t he vis ual ac uit y tec h nicia n  will use t he last ma nifest refracti o n perf or me d 
a n d deter mi ne t he S nelle n e q ui vale nt vis ual ac uit y  usi n g t he l o g Mar c hart. If t here is a 2-li ne 
or m ore re d ucti o n i n vis ual ac uit y fr o m t he last B C V A perf or me d, a re peat ma nifest 
refracti o n i n b ot h e yes a n d B C V A will be perf or me d. 
P ac h y metr y : C or neal t hic k ness usi n g ultras o u n d (c o ntact) pac h y metr y will be perf or me d o n 
t he ce ntral c or nea. T he sa me i nstr u me nt will be use d t hr o u g h o ut t he st u d y f or a gi ve n patie nt. 
C o ntact pac h y metr y will be perf or me d after I O P meas ure me nt. 
Vis u al fiel d test : Vis ual fiel d will be assesse d usi n g a ut o mate d peri metr y ( usi n g eit her 
H u m p hre y 2 4- 2 f ull t hres h ol d pr o gra m or SI T A Sta n dar d). T he sa me test met h o d ol o g y m ust 
be use d t hr o u g h o ut t he e ntire st u d y f or a gi ve n patie nt. 
Bi o micr osc o pic slit l a m p e x a mi n ati o n : Bi o micr osc o pic e xa mi nati o ns will be perf or me d 
usi n g a slit la m p. T he e xa mi nati o ns will i ncl u de  e val uati o n of t he c o n diti o n of t he e yeli ds, 
c o nj u ncti va (i ncl u di n g assess me nt of ble b c h aracteristics), c or nea (i ncl u di n g assess me nt f or 
c or neal str o mal e de ma at t he X E N Gel I m pla nt l ocati o n), a nteri or c ha mber, iris/ p u pil, a n d 
le ns, a n d assess me nt of Gel I m pla nt place me nt. 
G o ni osc o p y : Iri d oc or neal a n gle assess me nts will i ncl u de S haffer gra de; p ost o perati ve 
g o ni osc o p y will i ncl u de de vice dis place me nt, ma l p ositi o n, m o ve me nt, de vice c o ntact wit h 
c or nea a n d/ or iris, a n d de vice ti p occl usi o n. 
O p ht h al m osc o p y : T he stere osc o pic f u n d us assess me nts will be c o n d ucte d t hr o u g h a dilate d 
p u pil. N o n- dilate d o p ht hal m osc o p y ma y be perf or m e d if t he i n vesti gat or belie ves t hat p u pil 
dilati o n ma y p ut t he patie nt at ris k. T he e xa mi n ati o ns will i ncl u de e val uati o n of t he mac ula, 
vitre o us, a n d reti na. T he c u p/ disc rati o a n d prese nce of o ptic disc pat h ol o g y will be 
deter mi ne d usi n g stere osc o pic e val uati o n.  W h e n dilati o n is use d, o p ht hal m osc o p y s h o ul d be 
t he last e xa mi nati o n. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 3 9 of 5 9 
 
 
7. 3  
He alt h O utc o me Me as ures 
T he fre q ue nc y of s y m pt o ms will be assesse d usi n g a m o difie d versi o n of t he oc ular s y m pt o m 
q uesti o n naire desi g ne d f or t he c o lla b orati ve i nitial gla uc o ma treat me nt st u d y ( CI G T S), w hic h 
is referre d t o as t he patie nt oc ular s ym pt o ms q uesti o n naire wit hi n t his pr ot oc ol. 
All patie nts will be as ke d t o c o m plete t he Patie nt Oc ular S y m pt o ms Q uesti o n naire at 
scree ni n g a n d t he n a gai n at M o nt hs 3, 6, a n d 1 2. 
7. 4  
S u m m ar y of Met h o ds of D at a C ollecti o n 
Electr o nic data ca pt ure usi n g a vali date d electr o nic data ca pt ure s yste m ( E D C) will be use d 
t o c ollect st u d y-s pecific i nf or mati o n, s uc h as patie nt a n d i n vesti gat or assess me nts. T he data 
will be e ntere d o n t he e C R F i n a ti mel y ma n ner o n a n o n g oi n g basis. T he i n vesti gat or is 
res p o nsi ble f or e ns uri n g t hat data are pr o perl y rec or de d o n eac h patie nt’s e C R F a n d relate d 
d oc u me nts. A n i n vesti gat or w h o has si g ne d t he pr ot oc ol si g nat ure pa ge m ust re vie w a n d 
pers o nall y si g n f or t he e C R Fs (as i n dicate d i n t h e e C R Fs) t o e ns ure t hat t he fi n di n gs are 
rec or de d o n t he e C R Fs c orrectl y a n d c o m pletel y. T he desi g nate d m o nit or will s o urce- verif y 
t he data. I n vesti gat ors will pr o vi de access t o h ospital files, me dical r ec or ds, a n d ot her s o urce 
d oc u me nts c o ntai ni n g patie nt cli nical/ me dical i nf or mati o n.  
8.  
St atistic al Pr oce d ures 
A se parate statistical a nal ysis pla n will be pr e pare d t o pr o vi de s pecificati o ns f or all a nal yses. 
T he pla n will be fi nalize d a n d a p pr o v e d pri or t o cli nical data base l oc k. 
8. 1  
A n al ysis P o p ul ati o ns 
A n a nal ysis will be perf or me d after all i m pla nte d patie nts ha ve c o m plete d t he 1 2- m o nt h visit 
or e xite d t he st u d y a n d t he data base has bee n l oc ke d. 
I m pl a nte d p o p ul ati o n: T he i m pla nte d p o p ulati o n will i ncl u de all patie nts i m pla nte d wit h 
X E N. T his p o p ulati o n will be use d f or all pri mar y a n d sec o n dar y effecti ve ness a nal yses a n d 
all safet y a nal yses. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 0 of 5 9 
 
 
8. 2  
C ollecti o n/ Deri v ati o n of Pri m ar y a n d Sec o n d ar y Effecti ve ness 
Assess me nts 
T he pri mar y effecti ve ness meas ure, I O P, will be meas ure d usi n g a G ol d ma n n a p pla nati o n 
t o n o meter. T he meas ure me nts will be c ollecte d usi n g t he mas ke d e xa mi ner met h o d descri be d 
i n t he Pr ot oc ol Pr oce d ure Ma n ual. A d diti o nall y, t he n u m ber of c o nco mita nt I O P-l o weri n g 
me dicati o ns f oll o wi n g i m pla ntati o n will be rec or de d. To deter mi ne t he n u m ber of 
c o nc o mita nt I O P-l o weri n g me dicati o ns, fi xe d-c o m bi nati o n me dicati o ns will be c o u nte d as 
m ulti ple me dicati o ns. F or e xa m ple, C o m bi ga n will be c o u nte d as 2 me dicati o ns. A n y I O P 
meas ure me nts or me dicati o n c o u nts c ollecte d f oll o wi n g n o n-st u d y s ur gical pr oce d ures f or 
I O P c o ntr ol or de vice e x pla nt (ie, de vice fail ures) will be e xcl u de d fr o m t he a nal yses. 
8. 2. 1  
Pri m ar y Effecti ve ness Vari a ble 
T he pri mar y effecti ve ness e n d p oi nt is t he pr o p orti o n of patie nts ac hie vi n g at least a 
2 0 % re d ucti o n fr o m baseli ne H o ur 0 I O P w hile o n  t he sa me n u m ber or fe wer I O P-l o weri n g 
me dicati o ns at M o nt h 1 2 a n d is deri ve d fr o m t h e effecti ve ness varia bles: H o ur 0 I O P perce nt 
c ha n ge fr o m baseli ne a n d t he n u m ber of c o nc o mita nt I O P-l o weri n g me dicati o ns. T he H o ur 0 
I O P perce nt c ha n ge fr o m baseli ne is calc ulate d as 1 0 0 * ( H o ur 0 I O P c ha n ge fr o m baseli ne) / 
baseli ne H o ur 0 I O P.  
T he n u m ber of c o nc o mita nt I O P-l o weri n g me dicati o ns f oll o wi n g i m pla ntati o n will be 
c o m pare d wit h t he n u m ber pri or t o i m pla ntati o n. 
8. 2. 2  
Sec o n d ar y Effecti ve ness Vari a bles 
T he sec o n dar y effecti ve ness varia bles are H o ur 0 I O P, t he ass ociate d c ha n ge fr o m baseli ne, 
a n d t he n u m ber of c o nc o mita nt I O P-l o weri n g me dicati o ns. 
8. 2. 3  
Ot her Effecti ve ness Vari a bles 
Ot her effecti ve ness varia bles i ncl u de di ur nal I O P fl uct uati o n, t he ass ociate d c ha n ge fr o m 
baseli ne, t he reas o n f or de vice fail ure (s uc h as n o n-st u d y s ur gical pr oce d ures f or I O P c o ntr ol 
or de vice e x pla nt), a n d t he c ha n ge i n t he n u m ber of c o nc o mita nt I O P-l o weri n g me dicati o ns 
c o m pare d t o baseli ne.  A d diti o nal details re ga r di n g t he defi niti o n of de vice fail ure will be 
i ncl u de d i n t he a nal ysis pla n. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 1 of 5 9 
 
 
8. 3  
H y p ot hesis a n d Met h o ds of A n al ysis 
U nless ot her wise s pecifie d, c o nti n u o us varia bles will be s u m marize d b y descri pti ve statistics 
i ncl u di n g sa m ple size, mea n, sta n dar d de viati o n, me dia n, mi ni m u m, a n d ma xi m u m. 
Cate g orical varia bles will be s u m marize d b y fr e q ue nc y a n d perce nta ge. Statistical a nal yses 
will use 2-si de d 9 5 % CIs u nless ot her wise s pecifie d. 
8. 3. 1  
Pri m ar y Effecti ve ness A n al yses 
T he pri mar y effecti ve ness a nal ysis will es ti mate t he pr o p orti o n of patie nts, wit h 
c orres p o n di n g 2-si de d 9 5 % CI, t hat ac hie ve  at least a 2 0 % re d ucti o n fr o m baseli ne 
H o ur 0 I O P w hile o n t he sa me n u m ber or fe wer I O P-l o weri n g me dicati o ns at M o nt h 1 2 
c o m pare d wit h baseli ne usi n g a re peate d meas ures l o gistic re gressi o n m o del. T he m o del will 
i ncl u de visit a n d baseli ne I O P as fi xe d effects wit h data fr o m M o nt hs 1, 3, 6, 8, 1 0, a n d 1 2. 
A n u nstr uct ure d c o varia nce matri x will be use d f or re peate d meas ures o n t he sa me patie nt; if 
t he m o del wit h u nstr uct ure d c o varia nce fails t o c o n ver ge, a n alter nati ve c o varia nce str uct ure 
will be c h ose n. T he pri mar y effecti ve ness a nal ysis will be perf or me d usi n g t he i m pla nte d 
p o p ulati o n. 
8. 3. 2  
Sec o n d ar y Effecti ve ness A n al yses 
T he mea n a n d 2-si de d 9 5 % CI f or ra w I O P wit h t he c orres p o n di n g c ha n ge fr o m baseli ne will 
be esti mate d usi n g mi xe d effect m o del re peat  meas ure me nt i ncl u di n g all p ost- baseli ne visits 
wit h visit a n d baseli ne I O P as fi xe d effects wit h data fr o m M o nt hs 1, 3, 6, 8, 1 0, a n d 1 2. A n 
u nstr uct ure d c o varia nce matri x will be use d f or re peate d meas ures o n t he sa me patie nt; if t he 
m o del wit h u nstr uct ure d c o varia nce fails t o c o n v er ge, a n alter nati ve c o varia nce str uct ure will 
be c h ose n. A d diti o nall y, t he n u m ber of I O P-l o weri n g me dicati o ns will be s u m marize d b y 
visit wit h descri pti ve statistics ( mea n, sta n da r d de viati o n, mi ni m u m, ma xi m u m) a n d 2-si de d 
9 5 % CI f or t he mea n. T he sec o n dar y effecti v e ness a nal yses will be perf or me d usi n g t he 
i m pla nte d p o p ulati o n.  
8. 3. 3  
Ot her Effecti ve ness A n al yses 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 2 of 5 9 
 
 
8. 3. 4  
S afet y A n al yses 
Safet y a nal yses will be perf or me d usi n g t he i m pla nte d p o p ulati o n. T he n u m ber a n d 
perce nta ge of patie nts re p orti n g A Es will be ta b ulate d re gar dless of ca usalit y. A Es, a d verse 
de vice effects ( A D Es), B C V A, li ne c ha n ge i n B C V A fr o m baseli ne, bi o micr osc o pic slit la m p, 
a n d o p ht hal m osc o p y fi n di n gs will be s u m ma rize d b y fre q ue ncies at eac h visit. 
8. 4  
S u b gr o u p A n al yses 
N o s u b gr o u p a nal yses are pla n ne d. 
8. 5  
S a m ple Size C alc ul ati o n 
Fift y patie nts will pr o vi de a precisi o n of at l east ± 0. 1 4 5 t o esti mate t he pr o p orti o n of patie nts 
ac hie vi n g a n I O P re d ucti o n ≥ 2 0 % at 1 2 m o nt hs o n t he sa me n u m ber or fe wer I O P-l o weri n g 
me dicati o ns c o m pare d wit h baseli ne base d o n a 9 5 % e xact Cl o p per- Pears o n CI. Si xt y-fi ve 
patie nts will be i m pla nte d t o e ns ure at leas t 5 0 e val ua ble patie nts wit h 1 2 m o nt hs of 
f oll o w- u p.  
8. 6  
I nteri m A n al yses 
N o i nteri m a nal yses or re p orts are pla n ne d. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 3 of 5 9 
 
 
9.  
M ateri als  
9. 1  
St u d y Tre at me nt 
9. 1. 1  
Pr o d uct Descri pti o n 
T he X E N 4 5 Gla uc o ma Treat me nt S yste m is c o m prise d of t he X E N Gel I m pla nt (als o 
referre d t o as t he Gel I m pla nt) a n d t he X E N I nject or (als o referre d t o as t he I nject or). T he 
X E N Gla uc o ma Gel I m pla nt is i nte n de d t o creat e a c ha n nel t hr o u g h t he sclera all o wi n g fl o w 
of a q ue o us h u m or fr o m t he a nteri or c ha m ber i nt o t he s u bc o nj u ncti val s pace t o re d uce I O P. 
T he X E N Gel I m pla nt is i nserte d usi n g t he X E N I nject or via a n a b i nter n o  a p pr oac h, t hr o u g h 
a s mall c or neal i ncisi o n. 
T he X E N Gl a uc o ma Treat me nt S yste m is a ster ile, si n gle- use c o m p o ne nt. T he X E N I nject or 
is f or si n gle use o nl y a n d is n ot re usa ble. Re use ma y res ult i n c o nta mi nati o n, l oss of f u ncti o n, 
a n d ot her u n desira ble si de effects. T he pac ka ge m ust be e xa mi ne d t o verif y t he a p pr o priate 
m o del has bee n selecte d a n d pr o d uct ha s n ot e x pire d pri or t o i m pla ntati o n. 
T he i nsi de dia meter of t he t u be is a p pr o xi matel y 4 5 µ m, its o utsi de dia meter is 
a p pr o xi matel y 1 5 0 µ m, a n d it has a le n gt h of a p pr o xi matel y 6 m m.  
T he X E N Gel I m pla nt is c o m p ose d of a gelati n deri ve d fr o m p orci ne der mis, f or me d i nt o a 
t u be, a n d t he n cr oss-li n ke d wit h gl utaral deh y de. T he gelati n is desi g ne d t o e x pa n d a n d 
bec o me fle xi ble w he n h y drate d. T he e x pa nsi o n of t he t u be's o uter dia meter als o ai ds i n 
rete nti o n of t he Gel I m pla nt i n its i nte n de d l ocati o n after s ur gical i m pla ntati o n. 
T he X E N I nject or is a si n gle use mec ha nical deli ver y s yste m f or t he X E N Gel I m pla nt. T he 
Gel I m pla nt is prel oa de d i n t he X E N I nject or w hic h h o uses t he Gel I m pla nt d uri n g i nserti o n 
a n d deli ver y i nt o t he e ye. T he X E N I nject or all o ws t he s ur ge o n t o a d va nce a n d deli ver t he 
Gel I m pla nt t o t he desire d l ocati o n 
9. 1. 2  
I nstr ucti o ns f or Use a n d A d mi nistr ati o n 
A n i n vesti gati o nal directi o ns f or use (I D F U) br oc h ure will be pr o vi de d f or t he X E N 4 5 
Gla uc o ma Treat me nt S yste m. 
S ur gical trai ni n g will be re q uire d a n d pr o vi de d b y a n Aller ga n re prese ntati ve. 
Pr ot oc ol s pecific details o n a d mi nistrati o n will  be pr o vi de d i n t he Pr ot oc ol Pr oce d ure Ma n ual. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 4 of 5 9 
 
 
9. 2  
Ot her St u d y S u p plies 
T he f oll o wi n g s u p plies will be pr o vi de d b y Aller ga n or desi g nate d s u p pliers: 
•  S ur gical i nstr u me nts s pecific t o t he s ur ger y f or i m pla ntati o n of X E N, 
i ncl u di n g t he d ura ble s ur gical i nstr u me nts, t w o sizes of sterile, si n gle use 
bla des a n d t he o perati ve g o ni o le nses 
Sites t hat are n ot a ble t o recei ve s u p plies fr o m  Aller ga n d ue t o c o u ntr y re g ulati o ns will nee d 
t o pr o vi de t heir o w n s u p plies. 
1 0.  
St u d y A d mi nistr ati o n Pr oce d ures 
T he cli nical st u d y s hall n ot be gi n u ntil t he re q ui re d a p pr o vals fr o m t he a p pr o priate re g ulat or y 
a ut h orities a n d E Cs ha ve bee n o btai ne d. 
1 0. 1  
P atie nt E ntr y Pr oce d ures 
1 0. 1. 1  
O ver vie w of E ntr y Pr oce d ures 
Pr os pecti ve patie nts, as defi ne d b y t he criteria i n Secti o ns 5. 3  a n d 5. 4  (i ncl usi o n/e xcl usi o n 
criteria), will be c o nsi dere d f or e ntr y i nt o t his st u d y. A patie nt is c o nsi dere d t o ha ve e nr olle d 
i n t he st u d y u p o n si g ni n g t he i nf or me d c o nse nt, w hic h occ urs pri or t o a n y scree ni n g 
pr oce d ures. Scree ni n g pr oce d ures i ncl u de: 
•  C ollecti o n of de m o gra p hic i nf or mati o n 
•  C ollecti o n of me dical/s ur gical hist or y, i ncl u di n g o p ht hal mic a n d o p ht hal mic 
s ur gical hist or y. 
•  C o m pleti o n of Patie nt Oc ular S y m pt o ms Q uesti o n naire 
•  C ollecti o n of c o nc urre nt me dicati o ns (s yste mic a n d o p ht hal mic) a n d 
pr oce d ures 
•  E val uati o n of i ncl usi o n/e xcl usi o n criteria 
•  Uri ne pre g na nc y test (f or fe ma les of c hil d beari n g p ote ntial) 
•  A Es 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 5 of 5 9 
 
 
•  O p ht hal mic e val uati o n, w hic h i ncl u des t he f oll o wi n g: 
o  I O P 
o  Ma nifest refracti o n 
o  B C V A usi n g L o g Mar c hart  
o  Pac h y metr y 
o  Vis ual fiel d test 
o  Bi o micr osc o pic slit la m p e xa mi nati o n 
o  G o ni osc o p y 
o  O p ht hal m osc o p y  
N ote:  P h ot o gra p h y ( or vi de o rec or di n gs) are n o t re q uire d b y t he pr ot oc ol, b ut ma y be ta ke n 
as part of t he i n vesti gat ors’ sta n dar d practice, a n d t heref ore ma y be c ollecte d b y Aller ga n f or 
ge neral researc h, e d ucati o n, a n d/ or i nf or ma ti o nal p ur p oses. Patie nts c h o osi n g n ot t o all o w 
Aller ga n per missi o n t o use t hese p h ot o gra p h y or vi de o rec or di n gs ta ke n of t he m will n ot be 
e xcl u de d fr o m t he st u d y. 
1 0. 1. 2  
I nf or me d C o nse nt a n d P atie nt Pri v ac y 
T he p ur p ose, pr oce d ures, ris ks, be nefits, a n d alter nati ves t o st u d y pa rtici pati o n will be 
disc usse d wit h eac h p ote ntial patie nt. T he patie nt  m ust als o gi ve Data Pr otecti o n C o nse nt a n d 
ot her writte n d oc u me nt ati o n i n acc or da nce wit h  t he rele va nt c o u ntr y a n d l ocal pri vac y 
re q uire me nts ( w here a p plica ble) pri or t o a n y st u dy-relate d pr oce d ures or c ha n ge i n treat me nt. 
T he i n vesti gat or or his/ her a ut h orize d desi g n ee c o n d ucts t he i nf or me d c o nse nt disc ussi o n a n d 
will d oc u me nt i n t he patie nt’s me dical rec or ds t he ac q uisiti o n of i nf or me d c o nse nt a n d t he 
patie nt’s a gree me nt or ref usal t o n otif y his/ her pri mar y care p h ysicia n a b o ut t he st u d y. T he 
i nf or me d c o nse nt s hall i ncl u de all as pects of t he st u d y t hat are rele va nt t o t he patie nt’s 
decisi o n t o partici pate t hr o u g h o ut t he st u d y. T he i nf or me d c o nse nt pr ocess is t o a v oi d a n y 
c oerci o n or u n d ue i nfl ue nce o n, or i n d uce me nt of, t h e patie nt t o partici pat e. T he patie nt is t o 
pers o nall y si g n a n d date t he i nf or me d c o nse nt. T he i n vesti gat or will retai n t he ori gi nal c o p y 
of t he si g ne d f or m, a n d t he patie nt will recei ve a c o p y. U p o n si g ni n g t he i nf or me d c o nse nt 
f or m, t he patie nt is c o nsi dere d t o be e nr olle d i n t he st u d y a n d recei ves a patie nt n u m ber t hat 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 6 of 5 9 
 
 
will be use d o n all d oc u me ntati o n f or t he patie nt t hr o u g h o ut t he st u d y. Patie nt n u m bers will 
be assi g ne d i n asce n di n g or der, a n d n u m ber s will n ot be o mitte d or re use d. T he patie nt 
n u m ber is c o u ple d wit h t he site i de ntifica ti o n n u m ber f or u ni q ue i de ntificati o n of eac h 
patie nt. T he i n vesti gat or is t o e ns ure i m p or ta nt ne w i nf or mati o n is pr o vi de d t o ne w or 
e xisti n g patie nts t hr o u g h o ut t he st u d y. 
1 0. 1. 3  
Met h o d f or Assi g n me nt t o Tre at me nt Gr o u ps 
All eli gi ble patie nts will be assi g ne d t o treat m e nt wit h X E N. I n vesti g ati o nal pr o d uct will be 
la bele d wit h kit n u m bers t hat will be rec or de d o n t he e C R F. 
1 0. 2  
C o m pli a nce wit h Pr ot oc ol 
T he i n vesti gat or is res p o nsi ble f or c o m plia nce wit h t he pr ot oc ol at t he i n vesti gati o nal site. A 
re prese ntati ve of Aller ga n will ma ke fre q ue nt c o ntact wit h t he i n vesti gat or a n d his/ her 
researc h staff a n d will c o n d uct re g ular m o nit ori n g visits at t he site t o re vie w patie nt a n d 
de vice acc o u nta bilit y rec or ds f or c o m plia nce wit h  t he pr ot oc ol. A n y pr ot oc ol de viati o ns will 
be disc usse d wit h t he i n vesti gat or u p o n i de ntificati o n. All pr ot oc ol de viati o ns will be 
re p orte d t o t he E C acc or di n g t o t he E C’s re p orti n g re q uire me nts. 
1 0. 3  
Pre g n a nc y 
If a fe male bec o mes pre g na nt d uri n g t he st u d y, t he i n vesti gat or will n otif y Aller ga n 
i m me diatel y b y c o m pleti n g t he Pre g na nc y S ur veilla nce F or m after t he pre g na nc y is 
c o nfir me d a n d fa xi n g it t o t he a p pr o priate n u m be r o n t he fr o nt pa ge of t his pr ot oc ol. T he 
i n vesti gat or s hall ( 1) i nstr uct t he patie nt t o n otif y her p h ysician t hat t he y are bei n g treate d 
wit h a n i n vesti gati o nal de vice (ie, X E N) a n d ( 2 ) f oll o w t he pre g na nc y t o ter m. Best practices 
are t o be f oll o we d i n or der t o e ns ure t he welfare of t he patie nt a n d t he fet us. O nce t he 
pre g na nc y has reac he d ter m, t he sec o n d pa ge of t he Pre g na nc y S ur veilla nce F or m c o ncer ni n g 
o utc o me is t o be c o m plete d. T he me dical safe t y p h ysicia n will c o ntact t he i n vesti gat or t o 
o btai n i nf or mati o n a b o ut t he pre g na nc y o utc o me. T h e patie nt will c o nti n ue t o be f oll o we d as 
part of t he i m pla nte d p o p ulati o n b ut t he pre g na nc y will be d oc u me nte d as a pr ot oc ol 
de viati o n. Pre g na nc y b y itself will n ot be c o nsi dere d a n A E or seri o us a d verse e ve nt ( S A E). 
H os pitalizati o n f or a n or mal deli ver y or el ecti ve a b orti o n of a n or mal fet us d oes n ot 
c o nstit ute a n S A E. H o we ver, t he occ urre nce of  a n a d verse pre g na nc y o utc o me f or t he m ot her 
or c hil d ma y c o nstit ute a n A E or S A E, a n d t hese are t o be re p orte d as descri be d i n 
Secti o ns 1 1 . 3 t o 1 1 . 4. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 7 of 5 9 
 
 
1 0. 4  
St u d y Ter mi n ati o n 
If c o n diti o ns arise d uri n g t he stu d y t hat i n dicate t hat t he st u d y or  a n i n vesti gati o nal site nee ds 
t o be ter mi nate d, t he s p o ns or, i n vesti gat or, m o nit or, E C, a n d/ or re g ulat or y a ge ncies will 
disc uss t he sit uati o n a n d ta ke  a p pr o priate acti o n after c o nsultati o n. C o n diti o ns t hat ma y 
warra nt ter mi nati o n of t he st u d y or s ite i ncl u de, b ut are n ot li mite d t o: 
•  T he disc o ver y of a n u ne x pecte d, seri o us, or u nacce pta ble ris k t o patie nts 
e nr olle d i n t he st u d y 
•  T he decisi o n o n t he part of Aller ga n t o s us pe n d or disc o nti n ue testi n g, 
e val uati o n, or de vel o p me nt of t he st u d y de vice 
•  Fail ure of t he i n vesti gat or t o c o m pl y wit h perti ne nt nati o nal or state 
re g ulati o ns, E C-i m p ose d c o n diti ons, or pr ot oc ol re q uire me nts 
•  I n vesti gat or s u b missi o n of k n o wi n gl y false i nf or mati o n t o t he s p o ns or, 
m o nit or, E C, or a n y re g ulat or y a ge nc y 
Per I nter nati o nal Or ga nizati o n f or Sta n dar dizati o n (I S O) 1 4 1 5 5, if a st u d y is pre mat urel y 
ter mi nate d or s us pe n de d d ue t o safet y iss ues, Aller ga n s hall i nf or m all i n vesti gat ors a n d t he 
re g ulat or y a ut h orities of t he ter mi nati o n or s us pe nsi o n a n d t he reas o n(s) f or t he ter mi nati o n 
or s us pe nsi o n. T he E C is als o t o be i nf or m e d pr o m ptl y a n d pr o vi de d t he reas o n(s) f or t he 
ter mi nati o n or s us pe nsi o n b y Aller ga n or b y t he i n vesti gat or, as s pecifie d b y t he a p plica ble 
re g ulat or y re q uire me nts. If a pre mat ure ter mi nati o n or s us pe nsi o n occ urs, Aller ga n s hall 
re mai n res p o nsi ble f or pr o vi di n g res o urces t o f ulfill t he pr ot oc ol o bli gati o ns a n d e xisti n g 
a gree me nts f or f oll o w- u p of patie nts e nr olle d i n t he st u d y, a n d eac h i n vesti gat or or 
a ut h orize d desi g nee s hall pr o m ptl y i nf o r m e nr olle d patie nts, if a p plica ble. 
1 1.  
A d verse E ve nts 
T hr o u g h o ut t he c o urse of t he st u d y, all A Es will be m o nit ore d a n d re p orte d o n a n A E e C R F, 
i ncl u di n g seri o us ness, se verit y, acti o n ta ke n a n d relati o ns hi p t o stu d y treat me nt. If A Es occ ur, 
t he first c o ncer n will be t he safet y of t he st u d y patie nts. 
Alt h o u g h t he ris k of de vel o pi n g a seri o us c o m p licati o n is s mall, t he i n vesti gat or a n d t he 
researc h staff will m o nit or eac h patie nt cl osel y, a n d, if a c o m plicati o n occ urs, t he y will use 
t heir me dical j u d g me nt t o d o w hate ver is necessar y t o treat t he pr o ble m. A d diti o nal 
i nf or mati o n is a vaila ble i n t he I D F U. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 8 of 5 9 
 
 
T he f oll o wi n g ma y occ ur i n c o nj u ncti o n wit h t he use of t he X E N Gel I m pla nt: Gel I m pla nt 
mi grati o n, Gel I m pla nt e x p os ure or e xtr usi o n,  Gel I m pla nt bl oc ka ge, c h or oi dal eff usi o n or 
he m orr ha ge, h y p ot o n y mac ul o pat h y, ble b relate d c o m plicati o ns, or e n d o p ht hal mitis a n d ot her 
k n o w n c o m plicati o ns of i ntra oc u lar s ur ger y (e g, flat or s hall o w c ha m ber, h y p he ma, c or neal 
e de ma, mac ular e de ma, reti nal detac h me nt, vitre o us he m orr ha ge, u veitis).  
Sta n dar d of care s h o ul d be i m ple me nte d w he ne ver  a n A E occ urs t o treat a n d/ or res ol ve t he 
A E a n d t o m o nit or t he patie nt. T h e i n vesti gat or s h o ul d e ns ure t he s p o ns or is ke pt i nf or me d of 
all details relate d t o t he res ol uti o n a n d/ or pr o gressi o n of t he A E. A n y patie nt w h o is 
wit h dra w n fr o m t he st u d y d ue t o a n A E s hall be f oll o we d u ntil t he o utc o me is res ol ve d or, i n 
case of per ma ne nt i m pair me nt, u ntil t he e ve nt sta bilizes a n d t he o verall cli nical o utc o me has 
bee n ascertai ne d. 
1 1. 1  
Defi niti o ns 
1 1. 1. 1  
A d verse E ve nt 
A n A E is defi ne d i n acc or da nce wit h I S O 1 4 1 5 5 as “a n y u nt o war d me di cal occ urre nce, 
u ni nte n de d disease or i nj ur y, or u nt o war d cli nical si g ns (i ncl u di n g a b n or mal la b orat or y 
fi n di n gs) i n patie nts, users, or ot her pers o ns, w het her or n ot relate d t o t he i n vesti gati o nal 
me dical de vice.” T his defi niti o n i ncl u des e ve nts relate d t o t he i n vesti gati o nal me dical de vice 
or c o m parat or a n d e ve nts relate d t o t he pr o ce d ures i n v ol ve d e xce pt f or e ve nts i n users or 
ot her pers o ns, w hic h o nl y i ncl u de e ve nts relate d t o i n vest i gati o nal me dical de vices.  
Disease si g ns a n d s y m pt o ms t hat e xiste d pri or t o t he st u d y treat me nt are n ot c o nsi dere d A Es 
u nless t he c o n diti o n rec urs after t he patie nt has rec o vere d fr o m t he pre-e xisti n g c o n diti o n or 
t he c o n diti o n w orse ns i n i nte nsit y or fre q ue nc y d uri n g t he st u d y. 
A Es will be m o nit ore d t hr o u g h o ut t he st u d y be gi n ni n g wit h si g ni n g of i nf or me d c o nse nt. At 
eac h p ost- baseli ne visit, t he i n vesti gat or will be gi n q uer yi n g f or A Es b y as ki n g eac h patie nt a 
ge neral, n o n- directe d q uesti o n s uc h as “ Ha ve y o u ha d a n y c ha n ges t o y o ur c o n diti o n si nce 
y o ur last visit?” Pre vi o us A Es a n d c ha n ges i n  t hera p y/c o nc o mita nt me dicati o ns are t o be 
u p date d. Directe d q uesti o ni n g a n d e xa mi nati o n will t he n be d o ne as a p pr o priate. All 
re p orta ble A Es a n d cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs will be d oc u me nte d o n 
t he a p pr o priate e C R F. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 4 9 of 5 9 
 
 
1 1. 1. 2  
Seri o us A d verse E ve nt 
A n S A E is defi ne d i n acc or da nce wit h I S O 1 4 1 5 5 as a n A E t hat: 
1.  Le d t o deat h 
2.  Le d t o seri o us deteri orati o n i n t he healt h of t he patie nt, t hat eit her res ulte d i n: 
a. a life-t hreate ni n g ill ness or i nj ur y, or 
b.  a per ma ne nt i m pair me nt of a b o d y str uct ure or a b o d y f u ncti o n, or 
c. i n patie nt or pr ol o n ge d h os pitalizati o n, or 
d.  me dical or s ur gical i nter ve nti o n t o pre v e nt life-t hreate ni n g ill ness or i nj ur y 
or per ma ne nt i m pair me nt t o a b o d y str uct ure or a b o d y f u ncti o n, 
e. le d t o fetal distress, fetal deat h or a c o n ge nital a b n or malit y or birt h defect 
N O T E: Pla n ne d h os pitalizati o n f or a pre-e xisti n g c o n diti o n, or a pr oce d ure re q uire d b y t he 
pr ot oc ol, wit h o ut seri o us de teri orati o n i n healt h, is n ot c o nsi dere d a n S A E. 
See Secti o n 1 1 . 4 f or pr oce d ures f or re p orti n g a n S A E. 
1 1. 1. 3  
A d verse De vice Effect 
A n a d verse de vice effect ( A D E) is defi ne d i n acc or da nce wit h I S O 1 4 1 5 5 as “a n a d verse 
e ve nt relate d t o t he use of a n i n vesti gati o na l me dical de vice.” T his defi niti o n i ncl u des a n y 
A Es res ulti n g fr o m i ns ufficie nt or i na de q uate i nstr ucti o ns f or use, de pl o y me nt, i m pla ntati o n, 
i nstallati o n, or o perati o n, or a n y malf u ncti o n of t he i n vesti gati o nal me dical de vice as well as 
a n y e ve nt res ulti n g fr o m use err or ( per I S O 6 2 3 6 6) or fr o m i nte nti o nal mis use of t he 
i n vesti gati o nal me dical de vice. 
See Secti o n 1 1 . 3 f or pr oce d ures f or re p orti n g a n A D E. 
1 1. 1. 4  
Seri o us A d verse De vice Effect 
A seri o us a d verse de vice effect ( S A D E) is  defi ne d i n acc or da nce wit h I S O 1 4 1 5 5 as “a n 
a d verse de vice effect t hat has res ulte d i n a n y of t he c o nse q ue nces c haracteristic of a seri o us 
a d verse e ve nt.”   

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 0 of 5 9 
 
 
See Secti o n 1 1 . 4 f or pr oce d ures f or re p orti n g a S A D E. 
1 1. 1. 5  
U n a ntici p ate d Seri o us A d verse De vice Effect 
A n u na ntici pate d seri o us a d verse de vice effect ( U S A D E) is defi ne d i n acc or da nce wit h 
I S O 1 4 1 5 5 as “a n y seri o us a d verse de vice effect w hic h b y its nat ure, i ncide nce, se verit y, or 
o utc o me has n ot bee n i de ntifie d i n t he c urre nt versi o n of t he ris k a nal ysis re p ort.”  T he 
i n vesti gat or is t o c o ns ult t he I D F U f or a ntici pate d ris ks or a ntici pate d A Es. 
1 1. 1. 6  
De vice Deficie nc y 
A de vice deficie nc y is defi ne d i n acc or da n ce wit h I S O 1 4 1 5 5 as “i na de q uac y of a me dical 
de vice wit h res pect t o its i de ntit y, q ualit y, d u ra bilit y, relia bilit y, safet y, or perf or ma nce.” 
De vice deficie ncies i ncl u de malf u ncti o ns , use err ors, a n d i na de q uate la beli n g. 
If a de vice deficie nc y occ urs, t he i n vesti gat or will n otif y Aller ga n usi n g t he fa x n u m ber or 
e mail o n t he fr o nt pa ge of t he pr ot oc ol. De vi ce deficie ncies s hall be d oc u me nte d t hr o u g h o ut 
t he st u d y a n d a p pr o priatel y ma na ge d b y Aller ga n. Aller ga n s hall re vie w all de vice 
deficie ncies a n d deter mi ne a n d d oc u me nt i n writ i n g w het her t he y c o ul d ha ve le d t o a n S A D E. 
T hese s hall be re p orte d t o t he re g ulat or y a ut h orities a n d E Cs as re q uire d b y nati o nal 
re g ulati o ns.  
1 1. 1. 7  
Se verit y 
Se verit y is a cli nical deter mi nati o n of t he i nte nsit y of a n A E. T he se verit y assess me nt f or a 
cli nical A E is t o be c o m plete d usi n g t he f oll o wi n g defi niti o ns as g ui deli nes: 
Mil d  
A ware ness of si g n or s y m pt o m, b ut easil y t olerate d 
M o derate  
Disc o mf ort e n o u g h t o ca us e i nterfere nce wit h us ual acti vit y 
Se vere  
I nca pacitati n g wit h i na bilit y t o w or k or d o us ual acti vit y 
1 1. 1. 8  
Rel ati o ns hi p t o De vice or Pr oce d ure 
Relati o ns hi p t o a de vice refers t o a deter mi nati o n of t he relati o ns hi p (if a n y) bet wee n a n A E 
a n d t he de vice. A ca usal relati o ns hi p is prese nt if t he i n vesti gat or deter mi nes t hat t here is a 
reas o na ble p ossi bilit y t hat t he A E ma y ha ve bee n ca use d b y t he de vice. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 1 of 5 9 
 
 
A n A E c o ul d be c o nsi dere d pr oce d ure-relate d w h e n, i n t he j u d g me nt of t he i n vesti gat or, it is 
reas o na ble t o belie ve t hat t he e ve nt is ass ociate d wit h t he pr oce d ure, re gar dless of t he 
relati o ns hi p t o t he st u d y de vice. Pr oce d ure-relate d ca use s t hat c o ntri b ute t o t he occ urre nce of 
t he e ve nt ca n be attri b ute d t o ot her pr o d ucts, s ur gical tec h ni q ues, or me dicati o ns re q uire d 
s pecificall y f or t he pr oce d ure. 
Relati o ns hi p t o t he de vice or pr oce d ure m ust be  deter mi ne d b y t he i n vesti gat or a n d ca n n ot be 
dele gate d t o ot her st u d y staff. 
1 1. 2  
Ti meli nes f or Re p orti n g 
T he i n vesti gat or is t o a d here t o t he f oll o wi n g sc he d ule i n re p orti n g differe nt t y pes of A Es. 
A d verse 
E ve nt T y pe  
Re p orti n g t o Aller g a n  
St art of 
C ollecti o n  
E n d of C ollecti o n  
A Es, A D Es  
Rec or d o n A E e C R F u p o n a ware ness f or 
re vie w b y t he Cli nical M o nit or 
After si g ni n g 
of I C  
Last patie nt visit  
S A Es, S A D Es  
Rec or d o n S A E F or m a n d fa x t o Aller ga n 
wit hi n 2 4 h o urs of a ware ness  
After si g ni n g 
of I C  
Last patie nt visit  
A E = a d verse e ve nt; A D E = a d verse de vice effect; e C R F  = electr o nic case re p ort f or m; I C = i nf or me d 
c o nse nt; S A D E = seri o us a d verse de vice effect; S A E = seri o us a d verse e ve nt 
1 1. 3  
Pr oce d ures f or Re p orti n g a n A E or A D E 
All A Es or A D Es occ urri n g d uri n g t he st u d y peri o d ( be gi n ni n g wit h t he si g ni n g of i nf or me d 
c o nse nt) are t o be rec or de d o n t he a p pr o priate e C R F. A n y A E or A D E t hat is o n g oi n g at t he 
e xit visit m ust be f oll o we d u p as a p pr o priate. 
B ot h t he i n vesti gat or a n d Aller ga n will c o m pl y wit h all Me dical De vice Re p orti n g 
re q uire me nts. 
1 1. 4  
Pr oce d ures f or Re p orti n g a n S A E or S A D E 
All S A Es a n d S A D Es occ urri n g d uri n g t he st u d y peri o d ( be gi n ni n g wit h t he si g ni n g of 
i nf or me d c o nse nt) or f or at least 3 0 da ys after t he last st u d y visit are t o be i m me diatel y 
re p orte d t o a n Aller ga n re prese ntati ve at a p h o ne n u m ber/e mail a d dress liste d o n t he c o ver 
pa ge a n d rec or de d o n t he a p pr o priate e C R Fs.  All patie nts wit h a n S A E/ S A D E m ust be 
f oll o we d u p a n d t he o utc o mes re p orte d. T he i n vesti gat or is t o s u p pl y Aller ga n a n d t he E C 
wit h a n y a d diti o nal re q ueste d i nf or mati o n (e g,  h os pital disc har ge s u m mar y, a ut o ps y re p orts, 
a n d ter mi nal me dical re p orts). Aller ga n s h all e val uate all S A D Es a n d deter mi ne a n d 
d oc u me nt i n writi n g w het her t he y meet t he defi niti o n of U S A D E. T hese s hall be re p orte d t o 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 2 of 5 9 
 
 
all partici pati n g i n vesti gat ors,  t he re g ulat or y a ut h orities, a nd E Cs as re q uire d b y nati o nal 
re g ulati o ns. 
I n t he e ve nt of a n S A E/ S A D E, t he i n vesti gat or m ust: 
1.  N otif y Aller ga n i m me di atel y b y fa x usi n g t he S A E/ S A D E r e p orti n g f or ms. 
F or t he S A E/ S A D E fa x n u m ber, see t he fr o nt pa ge of t he pr ot oc ol. A n 
e mer ge nc y p h o ne n u m ber is als o o n t he fr o nt pa ge of t he pr ot oc ol. 
2.  O btai n a n d mai ntai n i n his/ her files all perti ne nt me dical rec or ds, i nf or mati o n, 
a n d me dical j u d g me nts fr o m c ollea g ues w h o assiste d i n t he treat me nt a n d 
f oll o w- u p of t he patie nt. 
3.  Pr o vi de Aller ga n wit h a c o m plete, writte n case hist or y t hat i ncl u des a 
state me nt as t o w het her t he e ve nt was or was n ot relate d t o t he use of t he 
i n vesti gati o nal de vice. 
4.  Pr o m ptl y i nf or m t he g o ver ni n g E C of t he e ve nt, if it is de vice-relate d. F or 
ot her S A Es, n otif y t he g o ver ni n g E C as  re q uire d b y t he E C, l ocal re g ulati o ns, 
a n d t he g o ver ni n g hea lt h a ut h orities. 
1 2.  
A d mi nistr ati ve Iss ues 
1 2. 1  
Pr otecti o n of H u m a n P atie nts 
1 2. 1. 1  
C o m pli a nce wit h I nf or me d  C o nse nt Re g ul ati o ns 
Writte n i nf or me d c o nse nt is t o be o btai ne d fr o m  eac h patie nt pri or t o e nr oll me nt i nt o t he 
st u d y, a n d/ or fr o m t he patie nt’s legall y a ut h orize d re prese ntati ve. 
1 2. 1. 2  
C o m pli a nce wit h E C Re g ul ati o ns 
T his st u d y is t o be c o n d ucte d i n acc or da nce wit h a p plica ble E C re g ulati o ns. T he i n vesti gat or 
m ust o btai n a p pr o val fr o m a pr o perl y c o nsti t ute d E C pri or t o i nitiati n g t he st u d y a n d 
rea p pr o val or re vie w at least a n n uall y. Aller ga n is t o be  n otifie d i m me diatel y if t he 
res p o nsi ble E C has bee n dis q ualifie d or if pr ocee di n gs lea di n g t o dis q ualificati o n ha ve be g u n. 
C o pies of all E C c orres p o n de nce wit h t he i n ve sti gat or are t o be pr o vi de d t o Aller ga n.  

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 3 of 5 9 
 
 
1 2. 1. 3  
C o m pli a nce wit h G o o d Cli nic al Pr actice 
T his pr ot oc ol is t o be c o n d ucte d i n c o m p lia nce wit h G C P g ui deli nes, a n d wit h et hical 
pri nci ples f or cli nical researc h t hat ha ve t heir ori gi n i n t he Declarati o n of Helsi n ki. 
1 2. 1. 4  
C o m pli a nce wit h Electr o ni c Rec or ds a n d Si g n at ure 
Re g ul ati o ns  
T his st u d y is t o be c o n d ucte d i n c o m plia nce wit h t he re g ulati o ns o n electr o nic rec or ds a n d 
electr o nic si g nat ure. 
1 2. 2  
C h a n ges t o t he Pr ot oc ol 
T he i n vesti gat or is n ot t o i m ple me nt a n y de viat i o n fr o m or c ha n ges t o t he pr ot oc ol wit h o ut 
a p pr o val b y Aller ga n a n d pri or re vie w a n d d oc u me nte d a p pr o val/fa v ora ble o pi ni o n fr o m t he 
E C of a pr ot oc ol a me n d me nt, e xce pt w here n ecessar y t o eli mi nate i m me diate hazar ds t o 
st u d y patie nts, or w he n t he c ha n ges i n v ol ve o nl y l o gistical or a d mi nistrati ve as pects of t he 
st u d y (e g, c ha n ge i n m o nit ors, c ha n ge of tele p h o ne n u m bers). Aller ga n ma y a me n d t he 
pr ot oc ol d uri n g t he c o urse of t he st u d y. T he a me n de d pr ot oc ol s hall be distri b ute d t o t he 
i n vesti gat ors a n d E Cs u p o n a p pr o val b y re g ulat or y a ut h orities. 
1 2. 3  
P atie nt C o nfi de nti alit y a n d Pri v ac y 
A re p ort of t he res ults of t his st u d y ma y be p u blis he d or se nt t o t he a p pr o priate healt h 
a ut h orities i n a n y c o u ntr y i n w hic h t he st u d y de vice ma y ulti matel y be mar kete d, b ut t he 
patie nt’s na me will n ot be discl ose d i n t hese d oc u me nts. T he patie nt’s na me ma y be discl ose d 
t o Aller ga n, t he g o ver ni n g healt h a ut h orities, or t he F D A, if t he y i ns pect t he st u d y rec or ds. 
A p pr o priate preca uti o ns will be ta ke n t o mai nta i n c o nfi de ntialit y of me dical rec or ds a n d 
pers o nal i nf or mati o n. 
Data Pr otecti o n C o nse nt, a n d ot her d oc u me ntati o n i n acc or da nce wit h t he rele va nt c o u ntr y 
a n d l ocal pri vac y re q uire me nts ( w here a p plica ble ) are t o be o btai ne d fr o m eac h patie nt pri or 
t o e nr oll me nt i nt o t he st u d y, a n d/ or fr o m t he patie nt’s le gall y a ut h or ize d re prese ntati ve i n 
acc or da nce wit h t he a p plica ble pri vac y re q uire me nts (e g,  E ur o pea n U ni o n [ E U] Data 
Pr otecti o n Directi ve 9 5/ 4 6/ E C [ E U Directi ve]). 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 4 of 5 9 
 
 
1 2. 4  
D oc u me nt ati o n 
1 2. 4. 1  
S o urce D oc u me nts 
S o urce d oc u me nts ma y i ncl u de a patie nt’s me dica l rec or ds, h os pital/cli nic c harts, la b orat or y 
n otes, de vice acc o u nta bilit y rec or ds, patie nt  q uesti o n naires a n d diaries, p h ot o gra p hic 
ne gati ves or di gital i ma ges, vi de o rec or di n gs, ra di o gra p hs, cli nic c harts, t he i n vesti gat or’s 
patie nt st u d y files, as well as t he res ults of di a g n ostic tests s uc h as X-ra ys, la b orat or y tests, 
a n d ma g netic res o na nce i ma gi n g. T he S A E F or m a n d Pre g na nc y S ur veilla nce F or m are als o 
c o nsi dere d s o urce d oc u me nts. T he i n vesti gat or’s c o pies of t he e C R Fs ser ve as part of t he 
i n vesti gat or’s rec or d of a patie nt’s st u d y-relate d data.  
T he f oll o wi n g i nf or mati o n is t o be e ntere d i nt o t he patie nt’s me dical rec or d: 
•  Patie nt’s na me 
•  Patie nt’s c o ntact i nf or mati o n 
•  Date t hat t he patie nt e ntere d t he st u d y a n d patie nt n u m ber 
•  St u d y title a n d/ or t he pr ot oc ol n u m ber a n d st u d y s p o ns or 
•  A state me nt t hat i nf or me d c o nse nt was o btai ne d, i ncl u di n g t he date a n d a 
state me nt t hat Data Pr otecti o n C o nse nt, or ot her c o u ntr y a n d l ocal patie nt 
pri vac y re q uire d d oc u me ntati o n f or t his st u d y has bee n o btai ne d, i ncl u di n g t he 
date 
•  Details of t he i m pla ntati o n pr oce d ure 
•  Dates of all patie nt visits 
•  All c o nc urre nt me dicati o ns ( List all prescri pti o n a n d n o n- prescri pti o n 
me dicati o ns bei n g ta ke n at t he ti me of e nr oll me nt. At eac h s u bse q ue nt visit, 
c ha n ges t o t he list of me dicati o ns are t o be rec or de d.) 
•  All c o nc urre nt me dical pr oce d ures 
•  Occ urre nce a n d stat us of a n y A Es 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 5 of 5 9 
 
 
•  Date t he patie nt e xite d t he st u d y, a n d a n otati o n as t o w het her t he patie nt 
c o m plete d t he st u d y or reas o n f or disc o nti n uati o n 
•  Res ults of la b orat or y tests perf or me d b y t he site (e g, res ults of uri ne 
pre g na nc y tests) 
1 2. 4. 2  
C ase Re p ort F or m C o m pleti o n 
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t hat  data are pr o perl y rec or de d o n eac h patie nt’s 
e C R Fs a n d relate d d oc u me nts. A n i n vesti gat or w h o has si g ne d t he pr ot oc ol si g nat ure pa ge or 
his/ her a ut h orize d desi g nee is t o pers o nall y si g n t he e C R Fs (as i n dicate d o n t he e C R F) t o 
vali date t hat t he o bser vati o ns a n d fi n di n gs  are rec or de d o n t he e C R Fs c orrectl y a n d 
c o m pletel y. T he e C R Fs are t o be s u b mitte d t o Aller ga n i n a ti mel y ma n ner at t he c o m pleti o n 
of t he st u d y, or as ot her wise s pecifie d b y Aller ga n. 
T he data re p orte d o n t he e C R Fs s hall be deri ve d fr o m s o urce d oc u me nts a n d be c o nsiste nt 
wit h t hese s o urce d oc u me nts, a n d a n y discre pa ncies s hall be e x plai ne d i n writi n g. A n y 
c ha n ge or c orrecti o n t o data re p orte d o n a n e C R F  s hall be date d, i nitiale d a n d e x plai ne d, if 
necessar y, a n d s hall n ot o bs c ure t he ori gi nal e ntr y (ie, a n a u d it trail s hall be mai ntai ne d); t his 
a p plies t o b ot h writte n a n d el ectr o nic c ha n ges or c orrecti o ns. 
1 2. 4. 3  
I n vesti g at or Re p orts 
I n acc or da nce wit h I C H E 6 4. 1 0 a n d 4. 1 3, t he i nvesti gat or is t o s u b mit writte n s u m maries of 
st u d y stat us t o t he E C a n n uall y ( or m ore freq ue ntl y if re q ueste d b y t he E C) a n d pr o m ptl y 
pr o vi de writte n re p orts t o Aller ga n, t he E C, a n d, w here re q uire d b y a p plica ble re g ulat or y 
re q uire me nts, t he i nstit uti o n re gar di n g a n y c ha n ges si g nifica ntl y affec ti n g t he c o n d uct of t he 
st u d y a n d/ or i ncreasi n g t he ris k t o patie nts. U p o n c o m pleti o n of t he st u d y a n d w here re q uire d 
b y t he a p plica ble re g ulat or y re q uire me nts, t he i n vesti gat or is t o i nf or m t he i nstit uti o n of t he 
c o m pleti o n of t he st u d y. T he i n vesti gat or/i nstit uti o n is t o pr o vi de Aller ga n wit h all re q uire d 
re p orts, t he E C wit h a s u m mar y of t he st u d y o utc o me, a n d t he re g ulat or y a ut h orities wit h a n y 
re p orts t he y re q uire of t he i n vesti gat or/i nstit uti o n. 
1 2. 4. 4  
Rete nti o n of D oc u me nt ati o n 
All st u d y-relate d c orres p o n de nce, patie nt rec or ds, c o nse nt f or ms, patie nt pri vac y 
d oc u me ntati o n, rec or ds of t he distri b uti o n a n d us e of all i n vesti gati o nal pr o d ucts, a n d c o pies 
of e C R Fs are t o be mai ntai ne d o n file. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 6 of 5 9 
 
 
Aller ga n-s pecific esse ntial d oc u me nts are t o be retai ne d u ntil at least 2 years after t he last 
a p pr o val of a mar keti n g a p plicati o n i n a n I C H re gi o n a n d u ntil t here are n o pe n di n g or 
c o nte m plate d mar keti n g a p plicati o ns i n a n I C H re gi o n or at least 2 years ha ve ela pse d si nce 
t he f or mal disc o nti n uati o n of cli nical de velo p me nt of t he i n vesti gati o nal pr o d uct. T hese 
d oc u me nts are t o be retai ne d f or a l o n ger pe ri o d, h o we ver, if re q uire d b y t he a p plica ble 
re g ulat or y re q uire me nts or if nee de d b y Aller ga n. 
Aller ga n re q uires n otificati o n i n  writi n g if t he i n vesti gat or wis hes t o st ore st u d y d oc u me nts 
off-site or t o reli n q uis h t he st u d y data rec or ds s o t hat m ut uall y a gree d- u p o n arra n ge me nts ca n 
be ma de f or tra nsfer of t h e data rec or ds t o a s uita bl y q ualifie d, res p o nsi ble pers o n. 
N otificati o n is t o g o t o Aller ga n Me dical, Att n: Cli nical Researc h De pt., 7 1 S o ut h L os 
Car ner os R oa d, G oleta, C A 9 3 1 1 7, U S A. 
1 2. 5  
L a beli n g, P ac k a gi n g, St or a ge, a n d Ret ur n of St u d y De vices 
1 2. 5. 1  
L a beli n g/ P ac k a gi n g 
All i n vesti gati o nal de vices will be clearl y la bele d “ F or I n vesti gati o nal Use O nl y.” 
1 2. 5. 2  
St or a ge of St u d y De vices 
All de vices will be st ore d a n d mai ntai ne d i n acc or da nce wit h t he c orres p o n di n g I D F U.  
T he st u d y de vice m ust be st ore d i n a sec ure area accessi ble t o dele gate d st u d y pers o n nel o nl y 
a n d a d mi nistere d o nl y t o patie nts e ntere d i nt o t he cli nical st u d y, at n o c ost t o t he patie nt, i n 
acc or da nce wit h t he c o n diti o ns s pecifie d i n t his pr ot oc ol. 
1 2. 5. 3  
St u d y De vice Acc o u nt a bilit y 
T he i n vesti gat or m ust kee p a n acc urate acc o u nti n g of t he n u m ber of st u d y de vices recei ve d 
fr o m Aller ga n, dis pe nse d t o patie nts, a n d ret ur ne d u n use d t o Aller ga n d uri n g a n d at t he 
c o m pleti o n of t he st u d y. A detaile d i n ve nt or y m ust be c o m plete d f or t he st u d y de vices 
dis pe nse d t o patie nts, i ncl u di n g patie nt i nitials, de vice serial/l ot n u m ber, date of i m pla ntati o n, 
a n d date of e x pla ntati o n if a p plica ble. T he st u d y pr o d uct m ust be dis pe nse d t o st u d y patie nts 
b y a n a p pr o priatel y q ualifie d pers o n a n d is t o be use d i n acc or da nce wit h t he pr ot oc ol u n der 
t he direct s u per visi o n of a st u d y i n vesti gat or. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 7 of 5 9 
 
 
1 2. 5. 4  
Ret ur n of St u d y De vices 
U p o n c o m pleti o n of t he st u d y, all u n use d X E N will be ret ur ne d t o Aller ga n u nless ot her 
arra n ge me nts f or dis p ositi o n are a gre e d u p o n i n writi n g wit h Aller ga n.  
I n t he e ve nt of X E N Gel I m pla nt e x pla ntatio n, c o ntact t he Aller ga n st u d y ma na ger f or 
i nstr ucti o ns. 
1 2. 6  
M o nit ori n g b y Aller g a n 
A p pr o priatel y trai ne d re prese ntati ves of Aller g a n will m o nit or t he c o n d uct of t he trial at eac h 
i n vesti gati o nal site, i ncl u di n g visits t o t he site t o re vie w, a u dit, a n d retrie ve c o pies of st u d y-
relate d d oc u me nts. It is t he res p o nsi bilit y of t he pri nci pal i n vesti gat or t o be prese nt or 
a vaila ble f or c o ns ultati o n a n d t o ass ure t hat Aller ga n has access t o all st u d y-relate d rec or ds 
d uri n g sc he d ule d m o nit ori n g visits. 
Aller ga n will re vie w de vice acc o u nta bilit y rec or ds a n d c o m pl ete d e C R Fs t o e ns ure 
c o m plete ness a n d c o nsiste nc y wit h t he s o urce rec or ds a n d c o m plia nce wit h t he pr ot oc ol 
re q uire me nts. 
Aller ga n re prese ntati ves will meet wit h t he i n ve sti gat or(s) a n d a p pr o priate staff at m ut uall y 
c o n ve nie nt ti mes t o disc uss st u d y-relate d data a n d q uesti o ns. 
1 2. 7  
P u blic ati o ns 
T his st u d y will be re gistere d a n d res ults p oste d o n w w w.cli nicaltrials. g o v. Aller ga n, as t he 
s p o ns or, has pr o prietar y i nterest i n t his stu d y. A ut h ors hi p a n d ma n uscri pt c o m p ositi o n will 
reflect j oi nt c o o perati o n bet wee n st u d y i n vesti gators a n d Aller ga n pers o n nel. A ut h ors hi p will 
be esta blis he d pri or t o t he writi n g of t he ma n us cri pt. As t his st u d y i n v ol ves m ulti ple ce nters, 
n o i n di vi d ual p u blicati o ns will be all o we d pri or t o c o m pleti o n of t he fi nal re p ort of t he 
m ultice nter st u d y e xce pt as a gree d wit h Aller ga n.  
1 2. 8  
C o or di n ati n g I n vesti g at or 
A si g nat or y c o or di nati n g i n vesti gat or will be desi g nate d pri or t o t he writi n g of t he Cli nical 
St u d y Re p ort. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 8 of 5 9 
 
 
1 3.  
Refere nces 
A merica n Ass ociati o n of O p ht hal m ol o g y. Cli n ical E d ucati o n: A n gle Cl os ure Gla uc o ma. 
[ u p date d 2 0 1 3 Dec 1 3]. Availa ble fr o m: htt ps:// w w w.aa o. or g/ m u n nerl y n-laser-s ur ger y-
ce nter/a n glecl os ure- gla uc o ma- 1 9. Accesse d 2 6 J ul 2 0 1 7. 
Az uara- Bla nc o A, B urr J, Ra msa y C, C o o per D, F oster PJ, Frie d ma n D S, et al. Effecti ve ness 
of earl y le ns e xtracti o n f or t he treat me nt of  pri mar y a n gle-cl os ure gla uc o ma ( E A G L E): a 
ra n d o mise d c o ntr olle d trial. La ncet. 2 0 1 6; 3 8 8: 1 3 8 9- 1 3 9 7. 
Az uara- Bla nc o A, B urr J M, C oc hra n C, Ra msa y C, Vale L, F oster P, et al. T he effecti ve ness 
of earl y le ns e xtracti o n wit h i ntra oc ular le ns i m pla ntati o n f or t he treat me nt of pri mar y a n gle-
cl os ure gla uc o ma ( E A G L E): st u d y pr ot oc ol f o r a ra n d o mize d c o ntr olle d trial. Trials. 
2 0 1 1; 1 2: 1 3 3. 
C he n D Z, K o h V, S n g C, A q ui n o M C, C he w P. C o m plicati o ns a n d o utc o mes of pri mar y 
p hac otra bec ulect o m y wit h mit o m yci n C i n a m ulti-et h nic asia n p o p ulati o n. P L o S O ne. 
2 0 1 5; 1 0:e 0 1 1 8 8 5 2. 
C he n Y H, L u D W, C he n g J H, C he n J T, C he n C L. Tra bec ulect o m y i n patie nts wit h pri mar y 
a n gle-cl os ure gla uc o ma. J Gla uc o ma. 2 0 0 9; 1 8: 6 7 9- 6 8 3. 
E ur o pea n Gla uc o ma S ociet y. Ter mi n ol o g y a n d g ui deli nes f or gla uc o ma. 4t h e diti o n. Sa v o na, 
Ital y: P u blic o m m; 2 0 1 4. 
Fa n g A W, Ya n g XJ, Nie L, Q u J. E n d osc o picall y  c o ntr olle d g o ni os y nec hial ysis i n ma na gi n g 
s y nec hial a n gle-cl os ure gla uc o ma. J Gla uc o ma. 2 0 1 0; 1 9: 1 9- 2 3. 
F oster PJ. T he e pi de mi ol o g y of pri mar y a n gle cl os ure a n d ass ociate d gla uc o mat o us o ptic 
ne ur o pat h y. Se mi n O p ht hal m ol. 2 0 0 2; 1 7: 5 0- 5 8. 
Ge d de SJ, Her n d o n L W, Bra n dt J D, B u de nz  D L, Fe uer WJ, Sc hiff ma n J C, et al. 
P ost o perati ve c o m plicati o ns i n t he T u be Ve rs us Tra bec ulect o m y ( T V T) st u d y d uri n g fi ve 
years of f oll o w- u p. A m J O p ht hal m ol. 2 0 1 2; 1 5 3: 8 0 4- 8 1 4.e 1. 
Gr o ver D, Fl y n n W, Bas hf or d K, Le wis R, D u h YJ, Na n gia R S, et al. Perf or ma nce a n d safet y 
of a ne w a b i nter n o gelati n ste nt i n refract or y gla uc o ma at 1 2 m o nt hs. A m J O p ht hal m ol. 
2 0 1 7; 1 8 3: 2 5- 3 6. 
Marc hi ni G, C he mell o F, Berza g hi D, Za m p ieri A. Ne w fi n di n gs i n t he dia g n osis a n d 
treat me nt of pri mar y a n gle-cl os ure gla uc o ma. Pr o g Brai n Res. 2 0 1 5; 2 2 1: 1 9 1- 2 1 2. 
Milla n F, Re ver o n M, G o nzalez L, Sis o M, S u esc u m C, N o vac k G, et al. E val uati o n of t he 
X E N 4 5 gel ste nt i n patie nts wit h pri mar y a n gle cl os ure gla uc o ma. P oster prese ntati o n at t he 
Ass ociati o n f or Researc h i n Visi o n a n d O p ht hal m ol o g y A n n ual C o nfere nce. Balti m ore, 
U nite d States 2 0 1 7. 

 
 
A p pr o v al D at e : 
 
 
0 4- O ct- 2 0 1 7
Aller ga n C o nfi de ntial 
Pr ot oc ol 1 9 2 4- 7 0 1- 0 0 7 
X E N 4 5 Gla uc o ma Tr eat me nt S yste m 
 
 
 
Pa ge 5 9 of 5 9 
 
 
M urt h y S K, Da mji K F, Pa n Y, H o d ge W G. Tra bec ulect o m y a n d p hac otra bec ulect o m y, wit h 
mit o m yci n- C, s h o w si milar t w o- year tar get  I O P o utc o mes. Ca n J O p ht hal m ol. 2 0 0 6; 4 1: 5 1- 5 9. 
Qi n g G, Wa n g N, M u D. Efficac y of g o ni os y nec h ial ysis f or a d va nce d c hr o nic a n gle-cl os ure 
gla uc o ma. Cli n O p ht hal m ol. 2 0 1 2; 6: 1 7 2 3- 1 7 2 9. 
Q ui gle y H A, Br o ma n A T. T he n u m ber of pe o pl e wit h gla uc o ma w orl d wi de i n 2 0 1 0 a n d 2 0 2 0. 
Br J O p ht hal m ol. 2 0 0 6; 9 0: 2 6 2- 2 6 7. 
R os ma n M, A u n g T, A n g L P, C he w P T, Lie b ma n n J M, Ritc h R. C hr o nic a n gle-cl os ure wit h 
gla uc o mat o us da ma ge: l o n g-ter m cli nical c o urse i n a N ort h A merica n p o p ulati o n a n d 
c o m paris o n wit h a n Asia n p o p ulati o n. O p ht hal m ol o g y. 2 0 0 2; 1 0 9: 2 2 2 7- 2 2 3 1. 
Sa he b H, Ge d de SJ, Sc hiff ma n J C, Fe uer WJ. T u be Vers us Tra bec ulect o m y St u d y Gr o u p. 
O utc o mes of gla uc o ma re o perati o ns i n t he T u be Vers us Tra bec ulect o m y ( T V T) St u d y. A m J 
O p ht hal m ol. 2 0 1 4; 1 5 7: 1 1 7 9- 1 1 8 9.e 2. 
S u n X, Dai Y, C he n Y, Yu D Y, Cri n gle SJ, C he n J, et al. Pri mar y a n gle cl os ure gla uc o ma: 
W hat we k n o w a n d w hat we d o n't k n o w. Pr o g Reti n E ye Res. 2 0 1 7; 5 7: 2 6- 4 5. 
Wa n g M, Fa n g M, Bai YJ, Z ha n g W Z, Li n M K, Li u B Q, et al. C o m paris o n of c o m bi ne d 
p hac otra bec ulect o m y wit h tra bec ulect o m y o nl y i n  t he treat me nt of pri mar y a n gle-cl os ure 
gla uc o ma. C hi n Me d J ( E n gl). 2 0 1 2; 1 2 5: 1 4 2 9- 1 4 3 3. 
Wei nre b R N, Frie d ma n D S, e dit ors. A n gle cl os ure a n d a n gle cl os ure gla uc o ma. Re p orts a n d 
c o nse ns us state me nts of t he 3r d gl o bal Ass o ciati o n of I nter nati o nal Gla uc o ma S ocieties 
( AI G S) c o nse ns us meeti n g o n a n gle cl os ure gla uc o ma. T he Ha g ue, Net herla n ds: K u gler 
P u blicati o ns; T he Net herla n ds 2 0 0 6. p. 1 1 2.  
1 4.  
Att ac h me nts 
N ot a p plica ble. 

 
 
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A L L E R G A N
A L L E R G A N
 
 
 
 
 
 
 
 
 
 
D at e ( D D/ M M M/ Y Y Y Y)/ Ti m e ( P T)  
Si g n e d b y:  
J u stifi c ati o n  
  
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
     
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
 
Pr ot o c ol 1 9 2 4- 7 0 1- 0 0 7
0 4- Oct- 2 0 1 7 1 8: 5 6 G M T- 0 7 0
Cli nical De vel o p me nt A p pr o val