A 12-Week, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Trial to Evaluate the Efficacy and Safety of AQX-1125 (200 mg) in Male Subjects With Chronic Prostatitis/Chronic Pelvic Pain Syndrome
Phase: PHASE2
Conditions: Chronic Prostatitis, Chronic Pelvic Pain Syndrome
Sponsor: Aquinox Pharmaceuticals (Canada) Inc.

V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 1 of 8 0
C L I NI C A L S T U D Y P R O T O C O L 
TI T L E P A G E 
Title:  
A 1 2 -W ee k, Ra n d o mize d, M ulti -Ce nter, D o u ble -Bli n d, Place b o -
C o ntr olle d, P arallel -Gr o u p, P hase 2 Trial t o E val uate t he Effi cac y a n d 
Safet y of A Q X -1 1 2 5 ( 2 0 0 m g) i n Male S u bj ects wit h C hr o nic 
Pr ostatitis/ C hr o nic P el vic P ai n S y n dr o me  
Test Pr o d uct:  
A Q X -1 1 2 5  
Pr ot oc ol I de ntific ati o n:  
A Q X -1 1 2 5 -2 0 5  
S p o ns or N a me, A d dress, a n d 
Tele p h o ne N u m b er:  
A q ui n o x P har mace uticals ( Ca na da) I nc.  
S uite 4 5 0 – 8 8 7 Great N ort her n W a y  
Va nc o u ver, B C   
Ca na da, V 5 T 4 T 5  
t: 6 0 4. 6 2 9. 9 2 2 3 
C o m pli a nce St ate me nt:  
T he trial will be c o n d ucte d i n acc or da nce wit h sta n dar ds of G o o d 
Cli nical Practice, as defi ne d b y t he I nter nati o nal C o u ncil f or 
Har m o nisati o n a n d all a p plica ble nati o nal a n d l ocal re g ulati o ns.  
D ate / Versi o n of Pr ot oc ol:  
 0 8 Marc h 2 0 1 8/ V ersi o n 3. 0, A me n d me nt  2 
A q ui n o x P h ar m ace utic als  
( C A N A D A) I nc. M e dic al M o nit or 
Alis o n E. Heal d , M D 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Si g nat ure  
 
 
 
 
 
Date:  
C o nfi de nti al I nf or m ati o n 
T he i nf or mati o n c o ntai ne d her ei n is c o nfi de ntial a n d ma y n ot be use d, di v ul ge d, p u blis he d, or ot her wise discl ose d 
wit h o ut t he pri or writte n c o ns e nt of A q ui n o x P har mace uticals ( Ca na da) I nc . 
0 8 M ar c h 2 0 1 8

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 of 8 0  
 
P R O T O C O L SI G N A T U R E P A G E  
Pr ot oc ol: A Q X - 1 1 2 5- 2 0 5 
Title:  A 1 2 - Wee k, R a n d o mize d, M ulti-Ce nter, D o u ble -Bli n d, Pl ace b o -C o ntr olle d, P a r allel -
Gr o u p, P h ase 2 Tri al t o E v al u ate t he Effic ac y a n d S afet y of A Q X- 1 1 2 5 ( 2 0 0 m g) i n M ale 
S u bjects wit h C hr o nic Pr ost atitis/ C hr o nic Pel vic P ai n S y n dr o me  
 
I n vesti g at or St ate me nt: I h a ve r ecei ve d a n d c o m pletel y re vie w e d t he a b o ve-na m e d pr ot oc ol, 
i ncl u di n g all a p p e n dices a n d a me n d me nts. As I n v esti gat or, I a gree t o c o n d uct t he trial i n 
acc or d a nce wit h all sti p ulati o ns of t he pr ot oc ol a n d i n acc or d a nce wit h t he I nter nati o nal C o u ncil 
f or Har m o nisati o n (I C H) G ui deli nes f or G o o d Cli nical Practices ( G C P), all a p plica ble nati o nal 
a n d l ocal re g ul ati o ns, t he Declar ati o n of Helsi n ki a n d its a me n d me nts. 
I N V E S TI G A T O R SI G N A T U R E A N D C O N T A C T I N F O R M A TI O N 
I n vesti g at or (si g n at ure) 
 
I n vesti g at or (ple ase pri nt ) 
 
D ate of Si g n at ure  
 
I n vesti g at or’s A d dress 
 
Cit y, St ate, C o u ntr y, Zi p C o de  
 
Tele p h o ne N o.  
 
F a x N o.  
 
E m ail  
 
Si g nat ure o n t his pa ge ass ures A q ui n o x  t hat, t o t he best of t he I n vesti gat or’s k n o wle d ge, t he affiliate d I nstit uti o nal 
Re vie w B oar d ( I R B) or I n de pe n de nt  Et hics C o m mittee (I E C) o perates i n acc or da nce wit h a p plica ble l ocal a n d 
nati o nal re g ulati o ns, a n d t hat t he I n vesti gat or u n dersta n ds a n d a grees t o a bi de b y all re g ulat or y o bli gati o ns a n d I C H 
G C P G ui deli nes w hile c o n d ucti n g t his cli nical trial.  
 
O nce si g ne d , t he ori gi nal of t his f or m s h o ul d be detac he d fr o m t he pr ot oc ol a n d ret ur ne d t o t he S p o ns or . 
( Ple ase ret ai n a c o py f or y o ur files) 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 of 8 0  
 
S T U D Y C O N T A C T I N F O R M A TI O N  
Seri o us A d verse E ve nts  a n d Tre at me nt E mer g e nt A d verse E ve nts of S peci al I nterest    
A n y S A E, or treat me nt e mer ge nt a d verse e v e nts of s pecial i nterest  (T E A E SI ) o cc urri n g i n a 
s u bject w hile recei vi n g st u d y dr u g or wit hi n 3 0 da ys of recei vi n g st u d y dr u g, e v e n t h o u g h t he 
e ve nt ma y n ot a p pear t o be st u d y dr u g relate d, m ust be pr o m ptl y re p orte d ( wit hi n 2 4 h o u rs) b y 
tele p h o ne, fa x, or e-m ail t o t he S p o ns or ( or desi g n ee).  
U nless ot her wise i nstr uct e d, S A E a n d T E A E SI re p orts are t o be s u b mitte d b y e m ail or fa x t o:  
C T D S Dr u g Saf et y Ma na ger  
E mail:  A q ui n o x P V G @cli nicaltrial data.c o m  
Fa x:  9 7 8. 4 8 6. 4 0 5 5 
Tel e p h o ne: 9 7 8. 4 8 6. 4 0 2 2 
 
W h o will f or war d a c o p y t o: 
Me dic al M o nit or:  
Alis o n Heal d , M D 
A q ui n o x Me dical M o nit or 
E mail: c o ns ulti n g @alis o n heal d.c o m  
Tele p h o ne: 2 0 6. 4 6 5. 3 9 1 2 
 
 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 of 8 0  
 
1  
S Y N O P SI S  
N a me of S p o ns or/ C o m p a n y: A q ui n o x P har mace uticals ( Ca na da) I nc.  
N a me of Pr o d uct:  A Q X -1 1 2 5  
N a me of Acti ve I n gre die nt:  A Q X -1 1 2 5  
Title:  A 1 2 -W ee k, Ra n d o mize d, M ulti -Ce nter, D o u ble -Bli n d, Place b o -C o ntr olle d, P arallel -Gr o u p, P hase 2 Trial  
t o E val uate t he Efficac y a n d S afet y of A Q X-1 1 2 5 ( 2 0 0 m g) i n Male S u bj ects wit h C hr o nic Pr ostatitis/ C hr o nic 
P el vic P ai n S y n dr o me  
De vel o p me nt P h ase:  2 
O bjecti ves:  
Pri m ary O bjective  
T he pri mar y o bj ecti ve of t his st u d y is t o e val uate t he effect of 1 2 wee k s of treat me nt wit h A Q X -1 1 2 5 ( 2 0 0  m g) 
a d mi nistere d orall y o nce -dail y c o m pare d t o place b o o n t he c ha n ge fr o m B aseli ne  (Visit  2) t o W ee k  1 2 ( Visit  4) i n 
ma xi m u m dail y pel vic pai n ( mea n) i n male s u bj ects wit h n o n -bacterial c hr o nic pr ostatitis/c hr o nic pel vic pa i n 
s y n dr o me ( C P/ C P P S) usi n g a sta n dar dize d 1 1-p oi nt N u meri cal Rati n g Scale ( N R S) pai n s c ore rec or de d dail y b y 
a n electr o nic diar y (e D iar y). 
Sec o n d ary O bjectives  
T he sec o n dar y o bj ecti ves of t his st u d y are t o e val uate:  
•  T he effects of 1 2 w ee ks of tre at me nt wit h A Q X-1 1 2 5 ( 2 0 0 m g) a d mi nistere d orall y o nce -dail y c o m pare d 
t o place b o o n t he c ha n ge fr o m B aseli ne  (Visit  2) t o W ee k 1 2 ( Visit  4) f or eac h of t he f oll o wi n g:  
o  
Nati o nal I nstit utes of Healt h C hr o nic Pr ostatitis S y m pt o m I n de x ( NI H -C P SI) pai n s u bscale a n d all 
d o mai ns t otal sc ore  
o  
Male se x ual healt h as meas ure d usi n g t he I nter nati o nal I n de x of Erectile F u ncti o n Q uesti o n naire, 
Erectile F u ncti o n D o mai n (II E F -E F)  
o  
A vera ge dail y pel vic pai n (e D iar y), a vera ge a n d ma xi m u m p el vic pai n ( P a per -base d  N R S,  i n cli nic), 
usi n g t he sta n dar dize d 1 1-p oi nt N R S  
o  
2 4 -h o ur v oi di n g  fre q ue nc y (e Diar y)  
•  Ti me c o urse of effects: A Q X -1 1 2 5 ( 2 0 0 m g) c o m pare d t o place b o o n t he c ha n ge fr o m B as eli ne  (Visit  2) at 
W ee k  6 ( Visit  3), W ee k  1 2 ( Visit  4), a n d W ee k  1 6 ( i.e. 4 w e e ks after e n d of treat me nt) f or eac h of t he pai n 
a n d s y m pt o m scale e n d p oi nts  
•  T he o verall res p o nse t o treat me nt f or A Q X -1 1 2 5 ( 2 0 0 m g) c o m pare d t o place b o as meas ur e d b y t he 
s u bj ect’s Gl o bal Res p o nse Assess me nt ( G R A), P atie nt’s Gl o bal I m pressi o n of C ha n ge sc ale ( P GI-C) a n d 
P atie nt’s Gl o bal I m pressi o n of Se verit y scale  ( P GI-S)  at W ee k  1 2 ( Visit  4)  
•  T he pr o p orti o n of s u bj ects wit h ≥3 0 % a n d ≥5 0 % i m pr o ve me nt i n ma xi m u m dail y pel vic pai n ( mea n) usi n g 
t he sta n dar dize d 1 1 -p oi nt N R S rec or de d b y t he e Diar y a n d t he NI H-C P SI pai n s u bscale c o m pare d t o 
place b o, at W ee k s 6 ( Visit 3) a n d 1 2  ( Visit 4) 
•  Res p o n der a nal ysis: r es p o nse t o treat me nt defi ne d b y a n y of t he f oll o wi n g:  
o  
Decrease i n ma xi m u m dail y p el vic pai n fr o m B aseli ne t o W ee k 1 2 (e Diar y) wit h n o c ha n ge i n t he 
a m o u nt or stre n gt h of c o nc o mita nt a na l gesic me dicati o ns 
o  
Decrease i n ma xi m u m dail y p el vic pai n fr o m B aseli ne t o W ee k 1 2 (e Diar y) wit h a decrease i n t he 
a m o u nt or stre n gt h of c o nc o mita nt a nal gesic me dicati o ns  
•  Disc o nti n uati o n of st u d y me di cati o n  d ue t o treat me nt fail ure ( % meeti n g treat me nt fail ure criteria a n d ti me 
t o e ve nt) 
S afety O bjectives  
T he safet y o bj ecti ves of t his st u d y are t o e val uate:  
•  Safet y a n d t olera bilit y of A Q X -1 1 2 5 ( 2 0 0 m g) c o m pare d t o place b o d uri n g t he 1 2 - wee k tr eat me nt peri o d 
•  Oc ular safet y base d u p o n assess me nt of le ntic ular o pacificati o n usi n g Le ns O paci ficati o n Classificati o n 
S yste m  ( L O C S) III, best c orrecte d vis ual ac uit y  ( B C V A) usi n g t he L o garit h m of t he Mi ni m u m A n gle of 
Res ol uti o n ( L o g M A R) c hart, intra oc ular p ress ure (I O P), c or neal stai ni n g, a n d slit la m p e xa mi nati o n  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 of 8 0  
 
N a me of S p o ns or/ C o m p a n y: A q ui n o x P har mace uticals ( Ca na da) I nc.  
N a me of Pr o d uct:  A Q X -1 1 2 5  
N a me of Acti ve I n gre die nt:  A Q X -1 1 2 5  
M et h o d ol o g y:  
I n t his d o u ble-bli n d, place b o -c o ntr olle d st u d y, a p pr o xi matel y 1 0 0 male s u bj ects dia g n ose d wit h C P/ C P P S will be 
ra n d o mize d t o eit her A Q X-1 1 2 5 ( 2 0 0 m g) or place b o i n a 1: 1 rati o acr oss a p pr o xi matel y  3 0  ce nters i n N ort h 
A merica. T he st u d y will c o nsist of a scree ni n g peri o d of u p t o 3 w ee ks, a 1 2- wee k treat me nt peri o d f oll o we d b y a 
4- w ee k Off-Treat me nt Safet y F oll o w -u p peri o d, a n d a n O p ht hal mic Safet y F oll o w -u p Visit  6 m o nt hs p ost last 
d ose, f or a t otal st u d y d urati o n of a b o ut 4 1 w ee k s. T here will als o be a f oll o w -u p tele p h o ne call 3  m o nt h s after 
t he last d ose.  
At Scree ni n g Visit  1, eac h s u bj ect will  c o m plete a set of q uesti o n naires , a n d recei ve (a n d be trai ne d t o use) a n 
e Diar y. S u bj ects will rec or d t heir a vera ge a n d ma xi m u m dail y pel vic pai n sc ore, at a p pr o xi matel y t he sa me ti me 
eac h da y (i n t he e ve ni n g  pri or t o t he last d ose of pai n me d icati o n), as well as t heir dail y use of a nal gesic pai n 
me dicati o ns. B aseli ne  o p ht hal mic assess me nts, i ncl u di n g le ntic ular o pacificati o n assess me nt usi n g L O C S III , ca n 
be c o m plete d as a se parate visit a n y ti me d uri n g t he scree ni n g peri o d (a n y ti me bef ore Visit 2) . 
At B aseli ne  (Visit  2), all s u bj ects will ret ur n t o t he cli nic f or re vie w of eli gi bilit y  a n d t o c o m plete t he efficac y 
q uesti o n naires a n d assess me nts t o esta blis h B aseli ne  val ues . A vera ge dail y pel vic pai n sc ores rec or de d i n t he 
e Diar y wit hi n t he  7 da ys pri or t o B aseli ne  (Visit  2) will be part of t he st u d y e ntr y criteria.  If all e ntr y criteria are 
met, t he s u bj ect will be ra n d o mize d ( 1: 1) t o recei ve a si n gle dail y oral d ose of 2 ta blets f or 1 2 wee ks as f oll o ws:  
•  A Q X -1 1 2 5 2 0 0 m g d ose gr o u p: 2 A Q X -1 1 2 5 1 0 0 m g ta blets ; or,  
•  Place b o  gr o u p: 2 place b o ta blets  
All e nr olle d s u bj ects will rec or d t he f oll o wi n g i n t he e Diar y (fr o m Scree ni n g Visit  1 t o  W ee k 1 6 [ Off -Treat me nt 
Safet y F oll o w -u p Visit ]): 
•  Ma xi m u m dail y pel vic pai n : su bj ects will assess t heir ma xi m u m pel vic pai n f or t hat da y o n a scale of 0 t o 
1 0, wit h 0 i n dicati n g ‘ n o pel vi c pai n’ a n d 1 0 i n dicati n g ‘ pel vic pai n as ba d as y o u ca n i ma gi ne ’ 
•  A vera ge dail y pel vic pai n. S u bj ects will assess t heir a vera ge pel vic pai n f or t hat da y o n a s cale of 0 t o 1 0, 
wit h 0 i n dicati n g ' n o pel vic pai n' a n d 1 0 i n dicati n g ' pel vic pai n as ba d as y o u ca n i ma gi ne'  
•  A nal gesic me dicati o n ta ke n eac h da y  
•  2 4 -h o ur v oi di n g  fre q ue nc y: voi di n g fre q ue nc y will be meas ure d o ver a 2 4 -h o ur peri o d, wit hi n a 3 -da y 
( 7 2-h o urs) wi n d o w bef ore t he ne xt sc he d ule d v isit (Visit 2, 3,  4 a n d Off -Treat me nt Safet y F oll o w - u p 
Visit ) 
At W ee k  6 ( Visit  3) , a n d W ee k  1 2  (Visit  4) , a n d W ee k 1 6 (Off -Treat me nt Safet y F oll o w -u p Visit ) d uri n g t he  
cli nic visit,  s u bj ects will c o m plete NI H-C P SI, pa per -base d 1 1 -p oi nt N R S  (a vera ge a n d ma xi m u m pel vic pai n 
e x perie nce d o ver t he last 2 4 h o urs ), G R A,  P H Q -9,  P GI -C, II E F, P GI -S, ha ve vital si g ns assesse d a n d ret ur n 
u n use d st u d y dr u g  ( W ee k 6 a n d  1 2) . An y  a d verse e ve nts ( A Es) are t o be rec or de d. 
S u bj ect c o m plia nce wit h t he e D iar y will be m o nit ore d b y trai ne d st u d y site pers o n nel at ea c h st u d y visit. 
All s u bj ects c o m pleti n g t he 1 2 w ee ks of treat me nt (Visit  4) will be c o nsi dere d c o m pleters of treat me nt. S u bj ects 
w h o wit h dra w fr o m t he st u d y d uri n g t he treat me nt peri o d s h o ul d c o m plete a n Earl y T er mi nati o n Visit . Su bj ects 
w h o disc o nti n ue t he d o u ble -bli n d treat me nt f or a n y reas o n will be e nc o ura ge d t o c o nti n ue wit h all s u bse q ue nt 
st u d y-relate d visits a n d e val uati o ns, wit h e m p hasis o n o btai ni n g pel vic pai n data, a nal gesic  me dicati o n data a n d 
v oi di n g  fre q ue nc y data t o assess efficac y e n d p oi nts. S u bj ects w h o c o m plete t he st u d y or earl y ter mi nate d uri n g 
t he st u d y will be as ke d t o ret ur n f or t he Safet y F oll o w-u p Visit  4 wee ks after disc o nti n ui n g st u d y dr u g, a n d t he 
O p ht hal mic Safet y F oll o w -u p Visit  6 m o n t hs after t he last d ose. S u bj ects will als o be c o nt acte d via tele p h o ne f or 
t he foll o w -u p tele p h o ne call 3  m o nt hs after t heir last d ose.  
N u m ber of S u bjects:  
A p pr o xi matel y 1 0 0 male s u bj ects  at a p pr o xi matel y 3 0 sites i n N ort h A merica . 
Di a g n osis a n d M ai n Cri teri a f or I ncl usi o n: 
I ncl usi o n Criteri a  
F or i ncl usi o n i nt o t he scree ni n g peri o d s u bj ects m ust meet t he f oll o wi n g criteria:  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 6 of 8 0  
 
N a me of S p o ns or/ C o m p a n y: A q ui n o x P har mace uticals ( Ca na da) I nc.  
N a me of Pr o d uct:  A Q X -1 1 2 5  
N a me of Acti ve I n gre die nt:  A Q X -1 1 2 5  
1.  Pr o vi de writte n i nf or me d c o ns e nt a n d t he willi n g ness a n d a bilit y t o c o m pl y wit h all as pects of t he st u d y 
re q uire me nts 
2.  Males, ≥1 8 a n d  ≤8 0 years of a ge at Scree ni n g Visit  1 
3.  Ha ve pai n or disc o mf ort i n t he pel vic re gi o n f or at least 3 m o nt hs i n t he last 6 m o nt hs, i n t he a bse nce of 
a uri nar y tract i nfecti o n  or ot her pel vic/ ur ol o gical ca use, a n d ha ve a p h ysicia n dia g n osis of C P/ C P P S 
( NI H Pr ostatitis Cate g or y III)  
4.  NI H -C P SI of ≥1 5 o n t he t otal sc ore  
5.  S u bj ects m ust a gree t o use a c o n d o m f or se x ual i nterc o urse fr o m Scree ni n g Visit  1 u ntil at least 9 0  da ys 
after t he last d ose of st u d y dr u g, u nless t he y ha ve bee n s ur gi call y sterilize d ( vasect o m y) f or a mi ni m u m 
of 6 m o nt hs . Tr ue a bsti ne nce fr o m se x ual i nterc o urse i n acc or da nce wit h t he preferre d a n d us ual 
lifest yle of t he s u bj ect is als o acce pta ble  
6.  Ha ve  a n a vera ge dail y pel vic pai n sc ore of ≥4 o ut of 1 0 o n t he 1 1 -p oi nt N R S pai n scale ( mea n of t he 
a vera ge dail y pel vic pai n sc ore rec or de d at eac h of t he 7 da ys pri or t o B aseli ne  [Visit  2]). A mi ni m u m of 
5 dail y rec or ds wit hi n 7 da ys pri or t o B aseli ne  (Visit  2) m ust be rec or de d  
7.  M ust be ca pa ble of v oi di n g i n de pe n de ntl y f or 3 0 da ys pri or t o scree ni n g (t o  all o w c o m pleti o n of 2 4 -h o ur 
v oi di n g diar y)  
E xcl usi o n Criteri a  
S u bj ects meeti n g a n y of t he f oll o wi n g criteria are i neli gi ble f or trial:  
1.  Dia g n osis of N I H Pr ostatitis C ate g ories I (ac ute pr ostatitis) or II ( c hr o nic bacterial ) p r ostatitis 
2.  Dia g n osis of i nterstitial c ystitis/ bla d der pai n s y n dr o me (I C/ B P S) wit h s y m pt o ms of pai n, press ure, or 
disc o mf ort percei ve d t o be relate d t o  t he bla d der, a n d ass ociate d l o wer uri nar y s y m pt o ms f or > 6 wee ks 
i n t he a bse nce of i nfecti o n or ot her i de ntifia ble ca uses 
3.  Relief o f pel vic  pai n after v oi di n g or ha ve > 1 5 v oi ds per da y  
4.  P ost -v oi d resi d ual v ol u me > 1 5 0 m L  
5.  Ha ve ha d a n u nres ol ve d ( p ositi ve bacterial uri ne c ult ure) uri nar y tract i nfecti o n  wit hi n 8 wee ks 
(i ncl usi ve) pri or t o Scree ni n g Visit  1 (s u bj ects ca n rescree n [ u p t o 1 ti me] o nce i nfecti o n clears) 
6.  Hist or y of pre vi o us pr ostate or bla d der i nter ve nti o n ( i.e. pr ostate bi o ps y , c yst osc o p y, or i n d welli n g 
uri nar y cat heter ) wit hi n 1 m o nt h of Scree ni n g Visit  1, hist or y of micr o wa ve t hera p y, tra ns uret hral 
resecti o n of t he pr ostate, tra ns uret hral ra di ofre q ue nc y t her m ot hera p y, tra ns uret hral i ncisi o n of t he 
pr ostate, tra ns uret hral nee dle a blati o n, tra ns uret hral laser va p orizati o n of t he pr ostate, Ur olift ® , Rez u m, 
a n d ot her ur ol o gical i nter ve nti o ns  (e. g., b ot uli n u m t o xi n) wit hi n 6 m o nt hs of Scree ni n g Visit  1 
7.  U nilateral testic ular or scr otal pai n as t he s ole s y m pt o m of C P/ C P P S  
8.  O n g oi n g, s y m pt o matic uret hral strict ure disease  
9.  Catastr o p hizi n g pai n sc ore of  ≥3 0 as deter mi ne d b y t he P ai n Catastr o p hizi n g Scale  ( P C S) 
1 0.  C urre nt maj or de pre ssi ve dis or der (i.e. P atie nt Healt h Q uesti o n naire - 9 [ P H Q-9]  sc ore ≥1 0)  
1 1.  Ne ur ol o gic disease or dis or der affecti n g t he bla d der, a bilit y t o v oi d s p o nta ne o usl y, or directl y 
c o ntri b uti n g t o uri nar y s y m pt o ms ( e. g., m ulti ple scler osis, a ut o n o mic ne ur o pat h y)  
1 2.  Se vere, e xcr uciati n g pai n d uri n g rectal e xa m ( i.e. a n “i na bilit y t o perf or m t he e xa m”)  
1 3.  Hist or y of c hr o nic s u bsta nce a b use, de pe n de nc y or a b use of o pi oi d s, or ot her narc otics wit hi n t he last 
2 years  
1 4.  C urre ntl y recei vi n g, or e x pect t o recei ve, a n y of t he f oll o wi n g pr o hi bite d me dicati o ns or pr oce d ures: 
•  N o n -ster oi d al a nti-i nfl a m m at or y dr u g or ot her me dic ati o n (e. g. al p h a -bl oc kers) f or C P/ C P P S, 
u nless o n a sta ble d ose f or ≥3 0 da ys pri or t o Scree ni n g Visit  1 
•  L o n g -acti n g o pi oi d s: wit hi n 2 wee ks pri or t o B aseli n e ( Visit 2) or e x pecte d t o ta ke a n y l o n g -acti n g 
o pi oi ds  at a n y ti me d uri n g t he st u d y  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 7 of 8 0  
 
N a me of S p o ns or/ C o m p a n y: A q ui n o x P har mace uticals ( Ca na da) I nc.  
N a me of Pr o d uct:  A Q X -1 1 2 5  
N a me of Acti ve I n gre die nt:  A Q X -1 1 2 5  
•  S h ort -acti n g o pi oi d  or o pi oi d -c o nt ai ni n g a n al gesic s: mor e t ha n 1 0  d oses/ m o nt h , or m or e t ha n a 
si n gle d ose > 2 da ys per wee k, or a n y s h ort-acti n g o pi oi d wit hi n 3 da ys pri or t o ra n d o mizati o n  
•  Or al ster oi d t her a p y, i m m u n os u p press a nts / i m m u n o m o d ul at ors  (i ncl u di n g dail y 
p h os p h o diesterase T y pe 4 i n hi bit ors) wit hi n 3 0 da ys pri or t o Scree ni n g Visit  1 a n d t hr o u g h o ut t he 
st u d y 
•  Ha ve ta ke n a n y i n vesti g ati o n al dr u g or de vice wit hi n  9 0 da ys pri or t o Scree ni n g Visit  1, or ha ve ha d 
pre vi o us e x p os ure t o A Q X -1 1 2 5  
1 5.  A n y p ri or hist or y of pel vic ca ncer (e. g., c ol orectal, ge nit o uri nar y) or treat me nt (ra diati o n or 
c he m ot hera p y) t here of  
1 6.  Maj or s ur ger y wit hi n 3 m o nt hs pri or t o Scree ni n g Visit  1 
1 7.  Ha ve a n y ot her c o n diti o n/ dise ase w hic h, i n t he o pi ni o n of t he I n vesti gat or, c o ul d c o m pr o mise s u bj ect 
safet y or i nterfere wit h t he s u bj ect’s partici pati o n i n t he st u d y or i n t he e val uati o n of t he st u d y res ults.  I n 
case of a n y d o u bt, t he I n vesti gat or s hall c o ns ult t he m e dical m o nit or.  
1 8.  K n o w n i nt olera nce t o micr o -cr ystalli ne cell ul ose ( A vicel ®  P H -1 0 2), ma n nit ol or ot her i n gr e die nt of  
A Q X -1 1 2 5 ta blets  
Test Pr o d uct, D ose a n d M o de of A d mi nistr ati o n:  
T w o A Q X -1 1 2 5 ( acti vat or of t he Src h o m ol o g y 2-c o ntai ni n g  i n osit ol-5' -p h os p hatase 1  pr otei n) 1 0 0  m g ta blets 
will be a d mi nistere d orall y o nce dail y  wit h a glass of water , ar o u n d t he sa me ti me of da y, f or 1 2 wee ks. T a blets 
s h o ul d be ta ke n wit h f o o d or eat a li g ht meal no m ore t ha n 4 h o urs pri or t o c o ns u m pti o n . 
Refere nce T her a p y, D ose a n d D ur ati o n of A d mi nistr ati o n:  
Matc hi n g place b o is i de ntical i n a p peara nce t o t he test pr o d uct a n d c o ntai ns n o acti ve i n gre die nt.  T w o place b o 
ta blets will be a d mi nistere d orall y o nce dail y wit h a glass of water , ar o u n d t he sa me ti me of da y, f or 1 2 wee k s. 
T a blets s h o ul d be ta ke n wit h f o o d or eat a li g ht meal n o m or e t ha n 4 h o urs pri or t o c o ns u m pti o n . 
D ur ati o n of Tre at me nt:  
S u bj ects will partici pate i n a 1 2 -wee k, d o u ble -bli n d treat me nt p hase. After t he treat me nt p hase, t here will be a 
4- wee k p ost last d ose Safet y F oll o w -u p, as well as a 6 -m o nt h p ost last d ose O p ht hal mic S afet y F oll o w -u p.  T here 
will als o be a 3- m o nt h p ost last d ose T ele p h o ne Call F oll o w -u p . 
V ari a bles:  
Pri m ar y E n d p oi nt  
T he pri mar y e n d p oi nt is t he  c ha n ge fr o m B aseli ne ( Visit 2) t o W ee k 1 2 ( Visit 4) i n t he ma xi m u m dail y pel vic 
pai n ( mea n)  usi n g a sta n dar dize d 1 1 -p oi nt N R S pai n sc ore rec or de d dail y b y  a n e Diar y. 
Sec o n d ar y E n d p oi nts  
T he sec o n dar y e n d p oi nts are : 
•  T he c ha n ge fr o m B aseli ne  t o W ee k 1 2 f or eac h of t he f oll o wi n g: 
o  
NI H -C P SI pai n s u bscale a n d all d o mai ns t otal sc ore  
o  
Male se x ual healt h  as meas ure d usi n g t he II E F-E F  
o  
Mea n of a vera ge d ail y pel vic p ai n sc ores (e Diar y), a vera ge a n d ma xi m u m pel vic pai n ( P a per -base d 
N R S i n cli nic) 
o  
2 4 - ho ur  v oi di n g  fre q ue nc y (e Diar y) 
•  Ti me c o urse of effects:  A Q X -1 1 2 5 ( 2 0 0 m g o nce -dail y ) c o m pare d t o place b o o n t he c ha n ge fr o m B aseli ne 
( Visit 2) t o W ee k 6 ( Visit 3), W ee k 1 2 ( Visit 4), a n d W ee k 1 6  (i.e. 4 wee ks after e n d of tr eat me nt) f or eac h 
of t he f oll o wi n g:  
o  
Mea n of ma xi m u m dail y pel vi c pai n  sc ore (e Diar y)  
o  
NI H -C P SI pai n s u bscale a n d all d o mai ns t otal s c ore 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 8 of 8 0  
N a me  of S p o ns or/ C o m p a n y: A q ui n o x P har mace uticals ( Ca na da) I nc.  
N a me of Pr o d uct:  A Q X -1 1 2 5  
N a me of Acti ve I n gre die nt:  A Q X -1 1 2 5  
o
II E F-E F
o
Mea n of a vera ge d ail y pel vic p ai n sc ores (eDiar y ), a vera ge a n d ma xi m u m pel vic pai n ( P a per -base d
N R S i n cli nic)
o
2 4- h o u r v oi di n g  fre q ue nc y (e Diar y)
•
R es p o nse t o treat me nt  c o m pare d t o place b o as meas ure d b y t he G R A, P GI - C, a n d P GI - S at W ee k 1 2  ( Visit
4)
•
A ≥3 0 %  an d ≥5 0 % i m pr o ve me nt i n ma xi m u m dail y pel vic p ai n ( usi n g t he 1 1 -p oi nt N R S rec or de d b y
e Diar y a n d t he NI H -C P SI pai n s u bscale) c o m pare d t o place b o, at W ee k 6  ( Visit 3) a n d Wee k 1 2 ( Visit 4)
•
Res p o n der a nal ysis: Res p o nse t o treat me nt defi ne d b y a n y of t he f oll o wi n g:
o
Decrease i n ma xi m u m dail y p el vic pai n fr o m B aseli ne t o W ee k 1 2 (e Diar y) wit h n o c ha n ge i n t he
a m o u nt or stre n gt h of c o nc o mita nt a nal gesic me dicati o ns
o
Decrease i n ma xi m u m dail y p el vic pai n fr o m B aseli ne t o W ee k 1 2 (e Diar y) wit h a decrease i n t he
a m o u nt or stre n gt h of c o nc o mita nt a nal gesic me dicati o ns
•
Disc o nti n uati o n of  st u d y me di cati o n d ue t o treat me nt fail ure ( % meeti n g treat me nt fail ure criteria a n d ti me
t o e ve nt)
S afet y E n d p oi nts  
T he safet y e n d p oi nts are : 
•
T he fre q ue nc y a n d se verit y of A Es will be re p orte d f or t he treat me nt p hase a n d will i ncl u d e:
o
A b n or mal, cli nicall y si g nifica nt vital si g ns, la b orat or y tests, electr ocar di o gra m ( E C G), wei g ht or
fin di n gs o n p h ysical e xa mi nati o ns
o
O p ht hal mic safet y  base d u p o n assess me nt of le ntic ular o pacificati o n usi n g L O C S III,  B C V A usi n g t he
L o g Mar c hart , I O P, c or neal stai ni n g a n d slit la m p e xa mi nati o n at B aseli ne , 1 2 w ee ks, a n d 6 m o nt hs
p ost last  d ose , a n d at Earl y T er mi nati o n ( E T ).
St atistic al M et h o ds:  
T his st u d y will i n vesti gate t he c o m parati ve treat me nt effect of A Q X -1 1 2 5  vers us place b o i n s u bj ects wit h 
C P/ C P P S . T he statistical a nal ysis will use i nfere ntial met h o ds (P  val ues) a n d esti mati o n ( p oi nt esti mates wit h 
c o nfi de nce i nter vals) t o e val uate t he effect of A Q X -1 1 2 5 c o m pare d t o place b o. T his st u d y is p o were d t o 
de m o nstrate a statisticall y si g nifica nt effect of A Q X -1 1 2 5  vers us place b o ( P  < 0. 0 5) i n t he pri mar y e n d p oi nt , if 
t he treat me nt effect is s ufficie ntl y lar ge. If a statisticall y si g nifica nt res ult is n ot o btai ne d b ut t he esti mate d effect 
pre dicts a statisticall y si g nific a nt effect i n a lar ger, s u bse q ue nt st u d y c o m pari n g A Q X -1 1 2 5  t o place b o, t his st u d y 
will be c o ns i dere d a s uccess. 
S a m ple Size a n d P o w er  
Sa m ple size was calc ulate d usi n g t he 2- sa m ple mea ns state me nt i n t he P O W E R pr oce d ure i n S A S. A sa m ple size 
of 4 5  s u bj ects per treat me nt gr o u p will pr o vi de  8 0 % p o wer t o detect a 1. 2 -p oi nt differe nce i n t he c ha n ge fr o m 
B aseli ne  ma xi m u m pel vic pai n sc ore bet wee n A Q X -1 1 2 5 a n d place b o ass u mi n g a bet wee n -s u bj ect sta n dar d 
de viati o n  of 2. 0 a n d a 2 -si de d 5 % si g nifica nce le vel.  
Ass u mi n g a 1 0 % rate of disc o nti n uati o n fr o m st u d y dr u g, t he t otal n u m ber of s u bj ects t o be ra n d o mize d is 
a p pr o xi matel y 1 0 0 . S u bj ects w h o disc o nti n ue will be i ncl u de d i n t he pri mar y a nal ysis, res ulti n g i n a sli g ht 
decrease i n p o wer if t he disc o nti n ui n g s u bj ects i n t he place b o gr o u p ha ve n o a d diti o nal c ha n ge after 
disc o n ti n uati o n of st u d y dr u g w hile t he disc o nti n ui n g s u bj ects i n t he A Q X -1 1 2 5 gr o u p ha ve a l oss of efficac y 
after disc o nti n ui n g st u d y dr u g.  
A n al ysis  
S u bject  pel vic  pai n  as assesse d by  the 1 1 - poi nt N R S  (e Diar y) will  be s u m marize d  at eac h we e k d uri n g t he  st u d y. 
A n al yses in t he  we e k pri or  to t he  Wee k  6 Visit , Wee k 12  Visit a n d Wee k 16  Visit ( Off-T reat me nt Safet y F oll o w -
U p)  will  be  pro d uce d wit h  mea n,  me dia n,  sta n dar d de viati o n, a n d q uartiles  for  b oth  pel vic  pai n  sc ore a n d  the 
c ha n ge fr o m  ba seli ne in pel vic  pai n  sc ore, usi n g th e mea n  of t he ma xi m u m  obser ve d  val ue fr o m  eac h of th e 7 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 9 of 8 0  
N a me  of S p o ns or/ C o m p a n y: A q ui n o x P har mace uticals ( Ca na da) I nc.  
N a me of Pr o d uct:  A Q X -1 1 2 5  
N a me of Acti ve I n gre die nt:  A Q X -1 1 2 5  
da ys  pri or t o eac h visit (B aseli ne , W ee k  6 , W ee k  1 2  a n d Wee k 1 6 ). T his  will  be rep orte d f or  ma xi m u m dail y 
pel vic  pai n  sc ore a n d  si milarl y f or a vera ge dail y  pel vi c pai n  sc ore. T he  pro p orti o n  of su bjects  w h o res p o n d t o 
treat me nt at Wee k  6, Wee k  1 2 a n d at Wee k 16  will  be s u m marize d.  Use of c onc o mita nt  a nal gesic me dicati o n 
will b e s u m marize d  wit h  the perce nta g e ( %) of  s u bjects ta ki n g eac h class of  me dicati o n  ( per mitte d sh ort -acti n g 
o pi oi d -c o ntai ni n g a nal gesics an d  n o n -o pi oi d  co ntai ni n g  anal gesics: e. g., aceta mi n o p he n)  an d  the dail y  dose 
( mea n, me dia n,  sta n dar d de viati o n, a n d quartiles,  usi n g  s u bjects w h o  to o k a n y s uc h me dicati o n o n at  least 1 of t he 
7 da ys  pri or to t he  B a seli ne, Wee k  6, Wee k  1 2 or  Wee k 1 6 Visit ). 
Ot her sec o n dar y e n d p oi nts will be s u m marize d at B aseli ne , W ee k  6, W ee k  1 2 , a n d W ee k  1 6, i ncl u di n g o bser ve d 
val ues at eac h ti me p oi nt a n d c ha n ge fr o m B aseli ne  at p ost- baseli ne ti me p oi nts, wit h mea n, me dia n, sta n dar d 
de viati o n , a n d q uartiles f or c o nti n u o us data , a n d c o u nts a n d perce nta ges f or cate g orical a n d bi nar y data.  
C o m paris o n of A Q X -1 1 2 5  t o place b o at W ee k  1 2 f or t he pri mar y efficac y e n d p oi nt will us e re peate d meas ures 
a nal ysis of varia nce t o c o m pare c ha n ge fr o m B aseli ne  i n ma xi m u m pai n sc ore ( N R S sc ore ) ( de pe n de nt varia ble) 
bet wee n treat me nt ar ms ( A Q X -1 1 2 5 a n d place b o). B aseli ne ma xi m u m pai n sc ore ( N R S s c ore ) will be i ncl u de d i n 
t he m o del as a c o variate. C ha n ge fr o m B aseli ne  t o W ee k  6 a n d W ee k  1 2 will be i ncl u de d  i n t he a nal ysis. A P  
val ue less t ha n or e q ual t o 0. 0 5 f or t he c ha n ge fr o m B aseli ne  at W ee k  1 2 will be c o nsi dere d statisticall y 
si g nifica nt. All ra n d o mize d s u bj ects will be i ncl u de d i n t he pri mar y a nal ysis.  
C o m paris o n of A Q X -1 1 2 5  t o place b o f or pr o p orti o n of s u bj ects w h o are res p o n ders will be use d t o f urt her 
u n dersta n d t he effect of A Q X -1 1 2 5  o n pel vic pai n. P  val ues f or t he test of e q ual n u m bers of res p o n ders i n eac h 
gr o u p will be re p orte d, wit h o ut a dj ust me nt f or m ulti plicit y, a n d use d descri pti vel y.  
Ot her sec o n dar y e n d p oi nts will be teste d i n a n a nal o g o us pr oce d ure, wit h P  val ues use d f or descri pti ve p ur p oses 
rat her t ha n f or statistical i nfere nce. 
Safet y data will be s u m marize d wit h n o i nfere ntial a nal ysis pla n ne d. A Es a n d treat me nt-e mer ge nt A Es ( T E A E) 
will be s u m marize d b y S yste m O r ga n C lass ( S O C) a n d Preferre d T er m ( P T) wit h c o u nts b y treat me nt gr o u p. 
O p ht hal m ol o gical fi n di n gs will be liste d a n d s u m marize d.  
D ate of t he S y n o psis:  0 8 Marc h 2 0 1 8  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
 
P a ge 1 0  of 8 0  
 
 
 
 
 
 
Fi g ure 1. A Q X -1 1 2 5 -2 0 5 st u d y desi g n fl o w c h art  
 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
 
P a ge 1 1  of 8 0  
 
 
 
 
T a ble 1 . A Q X -1 1 2 5 -2 0 5 Sc he d ule of E ve nts  
E ve nt  
Scree ni n g  Peri o d a 
B aseli ne  Tre at me nt P eri o d 
E T j 
S afet y F oll o w -u p  
Assess me nt  
Visit 1  
B aseli ne  O pt h al.  
Visit 1 a  
Visit 2  
Visit 3  
Visit 4  
Off -
T re at me nt  
Tele p h o ne 
c all k  
O p ht h al mic k  
Wee k  
 
 
1  
6  
1 2  
N A  
1 6  
2 5  
3 8  
D a y ( ± wi n d o w)  
-1 4  ( ±7)  
B ef ore Visit 2  
1  
4 2 ( ± 3)  
8 4 ( ±3)  
N A  
1 1 2 ( ±3)  
1 7 5 ( ±7)  
2 6 6 ( ± 7) 
I nf or me d co nse nt  
 
 
 
 
 
 
 
 
 
I ncl usi o n/ E xcl usi o n criteria 
 
 
 
 
 
 
 
 
 
Ra n d o mizati o n  
 
 
 
 
 
 
 
 
 
De m o gra p hics b 
 
 
 
 
 
 
 
 
 
Me dical/ S ur gical h ist or y 
 
 
 
 
 
 
 
 
 
P h ysical e xa mi nati o n  
 
 
 
 
 
 
 m  
 
 
U P OI N T classificati o n  
 
 
 
 
 
 
 
 
 
NI H -C P SI c  
 
 
 
 
 
 
 
 
 
P a per -base d 1 1 -p oi nt N R S c, d 
 
 
 
 
 
 
 
 
 
P C S c 
 
 
 
 
 
 
 
 
 
P H Q -9  c 
 
 
  
 n 
 n 
 n 
 n 
 
 
G R A c 
 
 
 
 
 
 
 
 
 
P GI -C c 
 
 
 
 
 
 
 
 
 
II E F, P GI-S c 
 
 
 
 
 
 
 
 
 
O p ht hal mic assess me nts e 
 
 
 
 
 
 
 m  
 
 
1 2 -lea d s u pi ne E C Gf 
 
 
 
 
 
 
 m  
 
 
Vital si g ns ( H R, B P , te m perat ure) 
 
 
 
 
 
 
 
 
 
Hei g ht  
 
 
 
 
 
 
 
 
 
W ei g ht  
 
 
 
 
 
 
 
 
 
Cli nical c he mistr y, g he mat ol o g y, uri nal ysis  
 
 
 
 
 
 
m  
 
 
Uri ne: bacterial c ult ure & se nsiti vit y, le u k oc yte 
esterase test  
 
 
 
 
 
 
 
 
 
2 4 -h o ur v oi di n g fre q ue nc y h 
 
 
 
 
 
 
 
 
 
A E c ollecti o n  
 
 
 
 
 
 
 
l 
l 
C o nc o mita nt me dicati o ns  
 
 
 
 
 
 
 
 
 
St u d y  dr u g dis pe nsi n g i 
 
 
 
 
 
 
 
 
 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
 
P a ge 1 2  of 8 0  
 
 
 
 
E ve nt  
Scree ni n g  Peri o d a 
B aseli ne  Tre at me nt P eri o d 
E T j 
S afet y F oll o w -u p  
Assess me nt  
Visit 1  
B aseli ne  O pt h al.  
Visit 1 a  
Visit 2  
Visit 3  
Visit 4  
Off -
T re at me nt  
Tele p h o ne 
c all k  
O p ht h al mic k  
Wee k 
 
 
1 
6 
1 2  
N A  
1 6  
2 5  
3 8  
D a y ( ± wi n d o w)  
-1 4  ( ±7)  
B ef ore Visit 2  
1  
4 2 ( ± 3)  
8 4 ( ±3)  
N A  
1 1 2 ( ±3)  
1 7 5 ( ±7)  
2 6 6 ( ± 7) 
St u d y dr u g c o m plia nce c hec k  
 
 
 
 
 
 
 
 
 
St u d y dr u g acc o u nta bilit y  
 
 
 
 
 
 
 
 
 
e Diar y Iss ue/ Trai n/ Re vie w/ C ollect  
I/ T 
 
R  
R  
R  
R  
R/ C  
 
 
A b bre vi ati o ns: A E =a d verse e ve nt; B C V A = best c orrecte d  vis ual ac uit y ; B P = bl o o d press ure; C =c ollect; E C G =electr ocar di o gra m; e Diar y =electr o nic di ar y; 
E T = Earl y T er mi nati o n; G R A = Gl o bal Res p o nse Assess me nt; H R = heart rate; I =iss ue; II E F  =I nter nati o nal I n de x of Erectile F u ncti o n; I O P =i ntra oc ular press ure; 
L O C S =  Le ns O pacit y Classifi cati o n S yste m ; L o g M A R = L o garit h m of t he Mi ni m u m A n gle of Res ol uti o n ; N A = n ot a p plic a ble; NI H -C P SI = Nati o nal I nstit ute of 
Healt h C hr o nic Pr ostatitis S y n dr o me I n de x; N R S = N u merical Rati n g Scale; P C S = P ai n Cat astr o p hizi n g Scale; P GI -C = P atie nt’s Gl o bal I m pr essi o n of C ha n ge 
scale; P GI-S = P atie nt’s Gl o bal I m pressi o n of Se verit y scale; P H Q -9 = P atie nt Healt h Q uesti o n naire; R =re vie w; T =trai n; U P OI N T = Uri nar y, Ps yc h os ocial, Or ga n 
S pecific, I nfecti o n, Ne ur ol o gi c/ S yste mic, T e n der ness of S keletal M uscles.  
a  
Mi ni m u m scree ni n g peri o d is 7 da ys , w hic h i ncl u des t he bas eli ne o p ht h al mic assess me nt at Visit 1a.  
b 
De m o gra p hics i ncl u de a ge, birt h year, se x, race a n d et h nicit y . 
c 
Q uesti o n naires m ust be c o m plete d pri or t o ot her assess me nts . 
d 
P a per -base d 1 1 -p oi nt N R S will be a d mi ni stere d i n-cli nic d uri n g t he st u d y visit  t o assess t he a vera ge a n d ma xi m u m dail y pel vic pai n .  
e 
O p ht hal mic assess me nts i ncl u de B C V A  usi n g t he L o g M A R c hart  (i.e. after ma nifest refracti o n), I O P ( prefera bl y meas ure d b y G ol d ma nn t on o metr y , bef ore 
a n d after dilati o n wit h m y driatic a ge nt) c or neal stai ni n g, slit la m p e xa mi nati o n , a n d le ntic ular o pacificati o n usi n g L O C S III. B aseli ne o p ht hal m ol o g y 
assess me nt ca n be c o m plete d as a se parate visit a n y ti me d uri n g t he scree ni n g peri o d (a n y ti me bef o re Visit 2). B ac k gr o u n d i nci de nce of cataracts i n s u bj ects 
n ote d pri or t o d osi n g s h o ul d be rec or de d as me dical hist or y.  O p ht hal mic assess me nts at all p ost -B aseli ne Visits s h o ul d oc c ur wit hi n t he s pecifie d Visit 
wi n d o ws.  
f 
S u bj ects will be resti n g s u pi ne f o r at least 5 mi n utes bef ore t he E C G rec or di n g. 
g 
Cli nical c he mistr y d oes n ot ne e d t o be fasti n g . 
h 
V oi di n g fre q ue nc y will be me as ure d o ver a 2 4 -h o ur peri o d, wit hi n a 3 -da y ( 7 2 h o urs) wi n d o w bef ore t he sc he d ule d visits . 
i 
T he first d ose of st u d y dr u g at B a seli ne (Visit  2) will be a d mi nistere d i n t he cli nic. At s u bs e q ue nt Visit s, s u bj ects are t o refrai n fr o m ta ki n g st u d y dr u g at 
h o me o n t he m or ni n g of t he cli nic visit  da y a n d s h o ul d be d ose d i n t he cli nic.  
j 
If a s u bj ect wit h dra ws fr o m t he st u d y, all assess me nts f or t he E T Visit  s h o ul d be c o n d ucte d. 
k 
S u bj ects w h o wit h dra w fr o m t he st u d y a n yti me d uri n g t he st u d y will ha ve a f oll o w -u p peri o d of 6 m o nt hs, c o nsisti n g of a n Off - Treat me nt S afet y F oll o w -u p 
V isit ( 4 wee ks p ost last d ose), tele p h o ne call f oll o w-u p  ( 3 m o nt hs p ost last d ose) a n d o p ht hal mic assess me nt ( 6 m o nt hs p ost last d ose) .  
l 
S u bj ects will be as ke d f or u p dates o n ne w a n d o n g oi n g (after t he 2 8 da ys f oll o w -u p) oc ular A Es o nl y . 
m  
Re peat at O ff- Treat me nt Safet y F oll o w-u p is o nl y nee de d if t here are o utsta n di n g safet y c o ncer ns fr o m W ee k  1 2 . 
n 
Sc ore will n ot be rec or de d i n t he data base , assess me nt will be perf or me d f or patie nt safet y/ m o nit ori n g p ur p oses o nl y cli nicall y si g nifica nt fi n di n gs will be 
re p orte d as a d verse e ve nts.  
N O T E: U nsc he d ule d visits ma y be c o n d ucte d at a n y ti me d uri n g t he st u d y a n d ma y  i ncl u d e t he sa me assess me nts as W ee k 1 2. 

A q ui n o x P har mace uticals ( Ca na da ) I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 1 3  of 8 0
 
 
 
2  
T A B L E O F C O N T E N T S  
TI T L E P A G E  .................................................................................................................................. 1 
P R O T O C O L SI G N A T U R E P A G E  ................................................................................................ 2 
S T U D Y C O N T A C T I N F O R M A TI O N  .......................................................................................... 3 
1  
S Y N O P SI S  .............................................................................................................................. 4 
2  
T A B L E O F C O N T E N T S  ...................................................................................................... 1 3 
3  
LI S T O F A B B R E VI A TI O N S A N D T E R M S ........................................................................ 1 8 
4  
I N T R O D U C TI O N ................................................................................................................. 2 0 
4. 1  
Bac k gr o u n d of Disease  ............................................................................................... 2 0 
4. 2  
Rati o nale f or Use of t he Pr o d uct ................................................................................. 2 0  
4. 2. 1  
N o ncli nical St u dies  ...................................................................................... 2 1 
4. 2. 2  
Cli nical E x perie nce  ...................................................................................... 2 3 
4. 2. 2. 1  Healt h y V ol u nteer St u dies  ............................................................ 2 3 
4. 2. 2. 2  Ast h ma St u d y  ................................................................................ 2 4 
4. 2. 2. 3  I nterstitial C ystitis/ Bla d der Pai n S y n dr o m e, C hr o nic O bstr ucti ve 
P ul m o nar y Disease, a n d At o pic Der matitis St u dies  ..................... 2 4 
5  
T RI A L O BJ E C TI V E S  ........................................................................................................... 2 5 
5. 1  
Pri mar y O bj ecti ve  ....................................................................................................... 2 5 
5. 2  
Sec o n dar y O bj ecti ves .................................................................................................. 2 5 
5. 3  
Safet y O bjecti ves  ........................................................................................................ 2 6 
6  
I N V E S TI G A TI O N A L P L A N ................................................................................................ 2 6 
6. 1  
O v erall Trial D esi g n a n d Pla n: Descri pti o n  ................................................................ 2 6 
6. 2  
Disc ussi o n of Trial Desi g n I n cl u di n g t he C h oice of C o ntr ol Gr o u p .......................... 2 8  
7  
S E L E C TI O N O F S U BJ E C T S  ............................................................................................... 2 8 
7. 1  
I n cl usi o n Criteria ........................................................................................................ 2 8 
7. 2  
E x cl usi o n Criteria ....................................................................................................... 2 8 
7. 3  
Criteria f or I n di vi d ual S u bject Disc o nti n uati o n of St u d y Dr u g .................................. 2 9  
7. 4  
Criteria f or I n di vi d ual S u bject Wit h dra wal fr o m t h e Trial  ......................................... 3 0 
8  
T R E A T M E N T S  ..................................................................................................................... 3 0 
8. 1  
A Q X - 1 1 2 5 Ta bl et Dr u g Pr o d uct ................................................................................. 3 0 
8. 2  
Place b o Ta blet Dr u g Pr o d uct  ...................................................................................... 3 0 
8. 3  
St u d y Dr u g  A d mi nistrati o n  ......................................................................................... 3 0 

A q ui n o x P har mace uticals ( Ca na da ) I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 1 4  of 8 0
 
 
 
8. 4  
Ra n d o mizati o n ............................................................................................................ 3 1  
8. 5  
St u d y Dr u g Bli n di n g  ................................................................................................... 3 2 
8. 6  
St u d y Dr u g Pac k a gi n g  ................................................................................................ 3 2 
8. 7  
St u d y Dr u g La b elli n g  .................................................................................................. 3 3 
8. 8  
St u d y Dr u g St ora ge  ..................................................................................................... 3 3 
8. 9  
St u d y Dr u g H a n dli n g a n d Acc o u nta bilit y................................................................... 3 3  
8. 1 0  Treat me nt a n d El ectr o nic Diar y C o m plia nce  ............................................................. 3 3 
8. 1 1  C o nc o mita nt Me dicati o ns ........................................................................................... 3 3  
8. 1 1. 1  
Per mitte d Me dicati o ns  ................................................................................. 3 3 
8. 1 1. 2  
Pr o hi bite d Me dicati o ns ................................................................................ 3 4  
9  
S T U D Y A S S E S S M E N T S  ..................................................................................................... 3 4 
9. 1  
Eli gi bilit y O nl y Assess m e nts  ...................................................................................... 3 4 
9. 1. 1  
De m o gra p hics, Bas eli ne C haracteristics, Me dical/ S ur gical Hist or y  ........... 3 4 
9. 1. 2  
Uri nar y, Ps yc h os ocial, Or ga n S pecific, I nfecti o n, Ne ur ol o gic/ S yste mic, 
Te n der n ess of S keletal M uscles Dia g n osis  .................................................. 3 4 
9. 1. 3  
Pai n Catastr o p hizi n g Scale  .......................................................................... 3 5 
9. 1. 4  
Patie nt Healt h Q uesti o n naire 9 -Q u esti o n  ..................................................... 3 5 
9. 1. 5  
Uri ne: Bacteri al C ult ure & Se nsiti vit y, Le u k o c yt e Esterase T est  ................ 3 5 
9. 2  
Efficac y Assess me nts .................................................................................................. 3 5 
9. 2. 1  
1 1- p oi nt N u merical Rati n g Scal e  ................................................................. 3 5 
9. 2. 2  
Nati o nal I nstit utes of Healt h, C hr o nic Pr ostatitis S y m pt o m I n d e x .............. 3 6 
9. 2. 3  
I nter nati o nal I n d e x of Erectile F u n cti o n Q uesti o n naire ............................... 3 6 
9. 2. 4  
Gl o bal Res p o nse Assess me nt ...................................................................... 3 6  
9. 2. 5  
Patie nt’s Gl o bal I m pressi o n of C ha n ge Scale .............................................. 3 6  
9. 2. 6  
Patie nt’s Gl o bal I m pressi o n of Se verit y Scale ............................................. 3 6 
9. 2. 7  
T we nt y -f o ur H o ur V oi di n g Fre q u e nc y ........................................................ 3 6 
9. 3  
Safet y Assess me nts  ..................................................................................................... 3 7 
9. 3. 1  
P h ysical E x a mi nati o n, Vital Si g ns  ............................................................... 3 7 
9. 3. 2  
O p ht hal mic Assess me nts  ............................................................................. 3 7 
9. 3. 3  
1 2- lea d S u pi ne Electr o car di o gra m ............................................................... 3 7 
9. 3. 4  
Cli nical C he mistr y & H e mat ol o g y/ Uri nal ysis  ............................................. 3 7 
9. 3. 5  
A d verse E v e nt Defi niti o ns/ Re p orti n g Re q uire me nts................................... 3 8  

A q ui n o x P har mace uticals ( Ca na da ) I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 1 5  of 8 0
 
 
 
9. 3. 5. 1  E x pecte d E ve nts  ............................................................................ 3 9 
9. 3. 5. 2  S us pecte d A d vers e Reacti o n  ......................................................... 3 9 
9. 3. 5. 3  A d verse Reacti o n  .......................................................................... 3 9 
9. 3. 5. 4  Seri o us A d verse E v e nt D efi niti o ns / Re p orti n g Re q uire me nts..... 3 9  
9. 3. 5. 4. 1  Seri o us A d verse E v e nt or Seri o us S us pecte d A d v erse 
Rea cti o n ...................................................................... 3 9 
9. 3. 5. 4. 2  Seri o us U ne x pecte d a n d S us pecte d A d vers e Reacti o n  4 0 
9. 3. 5. 5  O p ht hal mic E ve nt Re p orti n g ........................................................ 4 0  
9. 3. 5. 6  Rec or di n g A d verse E ve nts ............................................................ 4 1  
9. 3. 5. 7  Deter mi ni n g R elati o ns hi p of A d vers e E ve nts t o St u d y Dr u g ....... 4 2  
9. 3. 5. 8  Re p orti n g D eat hs a n d Ot her Seri o us A d verse E ve nts .................. 4 2  
9. 3. 5. 8. 1  E ve nts t o Be Re p ort e d a n d Ti mefra me  ....................... 4 2 
9. 3. 5. 8. 2  G o ver ni n g Re g ulat or y R e q uire me nts ......................... 4 2  
9. 3. 5. 9  I nitial I nf or mati o n Pr o vi de d b y t h e I n vesti gat or .......................... 4 3 
9. 3. 5. 1 0  F oll o w- u p I nf or mati o n  .................................................................. 4 4 
9. 3. 5. 1 1  Seri o us A d verse E v e nt a n d Seri o us a n d U ne x pect e d S us pecte d 
A d verse Reacti o n Re vie w a n d P ote ntial I m p act o n Trial C o n d uct
 ...................................................................................................... 4 4 
9. 4  
Ti mi n g of Assess me nts  ............................................................................................... 4 4 
9. 4. 1  
Scree ni n g Peri o d  .......................................................................................... 4 4 
9. 4. 1. 1  Visit 1  ............................................................................................ 4 4 
9. 4. 1. 2  Baseli ne O p ht hal mic Testi n g ( Visit 1a)  ........................................ 4 5 
9. 4. 2  
Baseli ne ( Visit 2)  ......................................................................................... 4 5 
9. 4. 3  
Treat me nt Peri o d  .......................................................................................... 4 6 
9. 4. 3. 1  Visit 3  ............................................................................................ 4 6 
9. 4. 3. 2  Visit 4  ............................................................................................ 4 6 
9. 4. 4  
Earl y Ter mi nati o n  ........................................................................................ 4 7 
9. 4. 5  
Safet y F oll o w - u p .......................................................................................... 4 7 
9. 4. 5. 1  Off -Treat me nt Safet y F oll o w - u p .................................................. 4 7 
9. 4. 5. 2  Tele p h o ne Call  .............................................................................. 4 8 
9. 4. 5. 3  O p ht hal mic  .................................................................................... 4 8 
9. 4. 5. 4  U nsc he d ule d Visit ......................................................................... 4 8  
1 0  S T A TI S TI C A L M E T H O D S A N D P L A N N E D A N A L Y S E S  .............................................. 4 8 
1 0. 1  Ge ner al C o nsi derati o ns ............................................................................................... 4 8  
1 0. 2  Sa m ple Size Deter mi nati o n ......................................................................................... 4 9 

A q ui n o x P har mace uticals ( Ca na da ) I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 1 6  of 8 0
 
 
 
1 0. 3  St u d y P o p ulati o ns ....................................................................................................... 4 9  
1 0. 4  Statistical A nal yses  ..................................................................................................... 4 9 
1 0. 4. 1  
S u bject Acc o u nta bilit y, De m o gra p hics, a n d Baseli ne C haracteristics ........ 4 9  
1 0. 4. 2  
Efficac y Data  ............................................................................................... 4 9 
1 0. 4. 2. 1  Wee kl y Sc ores base d o n Dail y Ass ess me nts  ................................ 5 0 
1 0. 4. 2. 2  Pri mar y Efficac y E n d p oi nt ........................................................... 5 0  
1 0. 4. 2. 3  Pri mar y Efficac y E n d p oi nt A nal ysis ............................................ 5 0  
1 0. 4. 2. 4  Sec o n dar y Efficac y E n d p oi nts ...................................................... 5 0  
1 0. 4. 2. 5  Sec o n dar y Efficac y E n d p oi nts A nal yses ...................................... 5 1  
1 0. 4. 2. 6  C o ntr ol f or M ulti plicit y ................................................................. 5 2 
1 0. 4. 2. 7  I nteri m a nal yses ............................................................................ 5 2 
1 0. 4. 3  
Safet y Data  ................................................................................................... 5 2 
1 1  Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  .................................................... 5 3 
1 2  D O C U M E N T A TI O N A N D I N S P E C TI O N S  ........................................................................ 5 3 
1 2. 1  St u d y M o nit ori n g ........................................................................................................ 5 3  
1 2. 2  A u dits a n d I ns p ecti o ns ................................................................................................ 5 4  
1 3  E T HI C A L A N D L E G A L I S S U E S  ........................................................................................ 5 4 
1 3. 1  Et hical C o n d uct/ G o o d Cli nical Practice  ..................................................................... 5 4 
1 3. 2  I nstit uti o nal Re vie w B oar d/I n d e pe n d e nt Et hics C o m mittee....................................... 5 4 
1 3. 3  Writte n I nf or m e d C o nse nt .......................................................................................... 5 4  
1 3. 4  Rec or ds a n d Cas e Re p ort F or ms ................................................................................. 5 5  
1 3. 5  Pr ot oc ol De viati o ns ..................................................................................................... 5 5  
1 3. 6  Ter mi nati o n of t he St u d y ............................................................................................ 5 5  
1 3. 7  Rete nti o n of Rec or ds................................................................................................... 5 5  
1 4  I N V E S TI G A T O R R E S P O N SI BI LI TI E S .............................................................................. 5 6 
1 5  R E F E R E N C E S  ...................................................................................................................... 5 8 
1 6  A P P E N DI C E S  ....................................................................................................................... 5 9 
A p pe n di x 1. Pa i n Catastr o p hizi n g Scale ............................................................................... 5 9 
A p pe n di x 2. Patie nt Healt h Q uesti o n naire 9- It e ms ............................................................... 6 1 
A p pe n di x 3. 1 1- p oi nt N u merical Rati n g Scale  ..................................................................... 6 4 
A p pe n di x 4. Nati o nal I nstit utes of Healt h C hr o nic Pr ostatitis S y m pt o m I n d e x ................... 6 6  
A p pe n di x 5. I nter n ati o nal I n de x of Erectile F u n cti o n Q uesti o n naire ................................... 6 8  
A p pe n di x 6. Gl o bal Res p o nse Assess me nt ........................................................................... 7 5  

A q ui n o x P har mace uticals ( Ca na da ) I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 1 7  of 8 0
 
 
 
A p pe n di x 7. Patie nt’s Gl o bal I m pressi o n of C ha n ge Scale .................................................. 7 7  
A p pe n di x 8. Patie nt’s Gl o bal I m pressi o n of Se verit y Scale ................................................. 7 9  
 
LI S T O F T A B L E S  
Ta ble 1. A Q X- 1 1 2 5- 2 0 5 Sc he d ule of E ve nts ............................................................................... 1 1  
Ta ble 2. A Q X- 1 1 2 5 Safet y acr oss P hase 2 Tri als (at Least 6 Wee ks of D osi n g) ......................... 2 5  
Ta ble 3. St u d y Dr u g D osi n g ......................................................................................................... 3 1  
Ta ble 4. Cli nical La b orat or y T ests  ................................................................................................ 3 8 
 
LI S T O F  FI G U R E S  
Fi g ure 1. A Q X- 1 1 2 5- 2 0 5 st u d y desi g n fl o w c hart ........................................................................ 1 0  
Fi g ure 2. T a blet pac k a gi n g  ........................................................................................................... 3 2 
 

A q ui n o x P har mace uticals ( Ca na da ) I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 1 8  of 8 0
 
 
 
3  
LI S T O F A B B R E VI A TI O N S A N D T E R M S  
A b bre vi ati o n  
Defi niti o n  
A D  
At o pic d er matitis  
A E  
A d verse e v e nt  
A N C O V A  
A n al ysis of C o varia n ce  
A L T  
Ala ni n e a mi n otra nsferase  
A P  
Al kali n e p h os p h atase  
A S T  
As p artate a mi n otra nsferase  
A U C  
Are a u n d er t h e c ur ve  
B C V A 
Best C orrecte d Vis u al Ac uit y  
B C R P 
Breast ca n cer resista n ce pr otei n  
B P 
Bl o o d press ure  
C 
C ollect  
C F R 
C o d e of Fe d eral Re g ulati o ns  
CI 
C o nfi d e n ce i nter val  
C ma x  
Ma xi m u m c o n ce ntrati o n  
C M H 
C o c hra n -Ma ntel -Hae nszel  
C P/ C P P S  
C hr o nic Pr ostatitis/ C hr o nic P el vic P ai n S y n dr o me  
C O P D  
C hr o nic o bstr u cti ve p ul m o n ar y disease  
C P K 
Creati n e p h os p h o ki n ase  
C R F 
Case Re p ort F or m  
D L  
Lact ati o n d a ys  
E C G 
Electr o car di o gra m  
e C R F 
Electr o nic Case Re p ort F or m  
e Diar y 
Electr o nic diar y  
E T  
Earl y Ter mi n ati o n  
F D A  
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  
GI  
Gastr oi ntesti n al  
G G T  
Ga m ma gl uta m yl tra ns p e pti d ase 
G R A  
Gl o b al Res p o nse Assess me nt  
H R  
Heart rate  
I 
Iss u e 
I B 
I n vesti gat or’s Br o c h ure 
I C/ B P S 
I nterstitial c ystitis / bla d d er p ai n s y n dr o me 
I C F 
I nf or me d C o nse nt F or m 
I C H 
I nter n ati o n al C o u n cil o n Har m o nisati o n, f or merl y calle d t h e I nter n ati o n al C o nfere n ce o n Har m o nisati o n 
I E C 
I nd e p e n d e nt  Et hics C o m mittee  
II E F 
I nter n ati o n al I n d e x of Erectile F u n cti o n Q u esti o n n aire 
II E F-E F  
I nter n ati o n al I n d e x of Erectile F u n cti o n Q u esti o n n aire, Erectile F u n cti o n D o main 
I N D 
I n vesti gati o n al Ne w Dr u g 
I O P 
I ntra o c ular press ure 

A q ui n o x P har mace uticals ( Ca na da ) I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 1 9  of 8 0
 
 
 
A b bre vi ati o n  
Defi niti o n  
I R B 
I nstit uti o n al Re vie w B o ar d 
I T T 
I nte nt-t o-Treat  
I V 
I ntra ve n o us 
I W R S 
I nteracti ve We b Res p o nse S yst e m 
L A R  
Late ast h matic res p o nse  
L D H  
Lact ate d e h y dr o ge n ase  
L o g M A R  
L o garit h m of t h e Mi ni m u m A n gl e of Res ol uti o n  
L O C S  
Le ns O p aci ficati o n Classificati o n S yst e m  
Me d D R A  
Me dical Dicti o n ar y f or Re g ulat or y Acti vities  
M M R M  
Mi xe d m o d el re p eate d meas ures  
N A  
N ot a p plica ble  
NI H - C P SI 
Nati o n al I nstit utes of Healt h  C hr o nic Pr ostatitis S y m pt o m I n d e x  
N O A E L  
N o o bser ve d a d verse effe ct le vel 
N R S  
N u meric al Rati n g Scale  
P C S  
P ai n Catastr o p hizi n g Scale  
P GI - C 
P atie nt’s Gl o b al I m pressi o n of C h a n ge scale  
P GI - S 
P atie nt’s Gl o b al I m pressi o n of Se verit y  scal e 
P- g p  
P er mea bilit y gl yc o pr otei n  
P H Q - 9 
P atie nt Healt h Q u esti o n n aire - 9 
P P  
P er Pr ot o c ol  
P T  
Preferre d ter m  
Q A  
Q u alit y Ass ura n ce  
S A E  
Seri o us a d verse e ve nt  
S A P  
Statistical a n al ysis pla n  
S HI P 1  
Src h o m ol o g y 2 -c o ntai ni n g i n osit ol -5' -p h os p h atase 1  
S O C  
S yst e m Or g a n Class  
S U S A R  
S us p ecte d U n e x p ecte d A d verse R eacti o ns  
t1/ 2 
Ter mi n al eli mi n ati o n h alf -life 
T E A E  
Treat me nt e mer g e nt a d verse e v e nt  
T E A E SI  
Treat me nt e mer g e nt a d verse e v e nt of s p ecial i nterest  
T ma x  
Ti me t o reac h ma xi m u m c o nce ntrati o n  
U P OI N T  
Uri n ar y, Ps yc h os o cial, Or ga n S p ecific, I nfe cti o n, Ne ur ol o gic/ S yste mic, Te n d er n ess of S keletal M uscles  
U S  
U nite d State s 
 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 0  of 8 0  
 
4  
I N T R O D U C TI O N 
A q ui n o x P har mace uticals ( Ca na da) I nc. ( A q ui n o x) is e val uati n g A Q X - 1 1 2 5, a n oral, s mall- 
m olec ule, a nti -i nfla m mat or y a ge nt f or t h e treat me nt of C hr o nic Pr ostatitis/ C hr o nic Pel vic Pai n 
S y n dr o me ( C P/ C P P S ) a n d other i nfla m mat or y dis eases.  
4. 1  
B ac k gr o u n d of Dise ase 
C hr o nic n o n bacteri al pr ostatitis (als o k n o w n as c hr o nic pel vic pai n s y n dr o me, C P/ C P P S) is a 
c o m m o n male ge nit o uri nar y c o n diti o n t hat ca us es pai n a n d i nfla m mati o n i n t he pr ostate, pel vis, 
a n d t he l o wer uri nar y tr act  (H ar v ar d P ers p e cti v es o n Pr ost at e Dis e as e, 2 0 1 7; R o d di c k et al ., 
2 0 1 7 ). T he pr e d o mi na nt s y m pt o m of C P/ C P P S is pai n i n t he s u pra p u bic area, peri n e u m a n d 
pe nis b ut ca n als o occ ur i n t he testes, l o wer bac k or gr oi n. Pai n o n ejac ulati o n is o ne of t he m ost 
pr o mi ne nt a n d b ot hers o me s y m pt o ms i n ma n y p atie nts. V oi di n g s y m pt o ms s uc h as ur ge nc y, 
fre q ue n c y a n d p o or i nterr u pte d uri nar y fl o w are c o m m o n al o n g wit h se x ual d ysf u n cti o n (Ni c k el, 
2 0 1 7 ). 
Of t he 3 cat e g ories of s y m pt o matic pr ostatitis defi ne d b y t he Nati o nal I nstit utes of Healt h ( NI H), 
C P/ C P P S  ( T y pe III) is t he m ost c o m m o n, acc o u nti n g f or a b o ut 9 0 % of all cases. N o k n o w n 
eti ol o g y has bee n esta blis he d, a n d wit h o ut a defi n e d ca usati ve a ge nt, treat me nt ma y b e g ui de d 
lar gel y b y a d oct or's cli nical e x perie nce a n d i nsti ncts rat her t ha n h ar d e vi de nce. Alt h o u g h n ot 
life-t hreat e ni n g, a dia g n osis of C P/ C P P S h ol ds t he p ote ntial f or a re d uce d q ualit y of life 
(H ar v ar d P ers p e cti v es o n Pr ost at e Dis e as e, 2 0 1 7 ). 
T he g o al of treat me nt is t o i m pr o ve s y m pt o ms . Alt h o u g h a nti bi otics ma y be prescri be d, little 
be nefit ma y r es ult as t he c o n diti o n ma y be c hr o nic a n d n ot ca use d b y a n acti ve i nfecti o n. Ot her 
c o m m o n treat me nts i ncl u de me dicati o ns t o rela x t he m uscles ar o u n d t he pr ostate a n d bla d der 
nec k  ( α-a dr e ner gic bl oc k er s), m uscle r ela x a nts or tric ycli c a nti de pressa nts, a n d prescri pti o n pai n 
me dicati o n or n o n- ster oi dal a nti-i nfla m mat or y dr u gs t o re d u ce p ai n a n d s welli n g. Alter n ati ve a n d 
nat ural re m e dies t hat ma y r e d uce o n g oi n g p ai n i ncl u de war m b at hs ; ac u p u nct ure; pel vic fl o or 
p h ysical t hera p y; r ela x ati o n e x ercises; massa ge t h era p y ; dietar y ma na ge m e nt ; a n d bi ofee d bac k 
(R o d di c k et al ., 2 0 1 7). 
4. 2  
R ati o n ale f or Use of t he Pr o d uct  
A Q X - 1 1 2 5 is bei n g de v el o pe d as a n o vel, s mall m olec ule f or t h e treat me nt of i nfla m mat or y 
diseases. A Q X -1 1 2 5 re pr ese nts a ne w p h ar mace utical class of c o m p o u n ds t hat acti vate t he Src 
h o m ol o g y 2-c o ntai ni n g i n osit ol- 5'- p h os p hatas e 1 ( S HI P 1 ) pr otei n, a m o d ul at or of 
p h os p h oi n ositi de si g nali n g f or di verse pr ocesses i ncl u di n g cell gr o wt h, acti vati o n, a n d 
i m m u ne/i nfla m mat or y r e g ulati o n (St e nt o n et al ., 2 0 1 3).  
O ne of t he f u n cti o ns of S HI P 1 is t he meta b olis m of p h os p hati d yli n osit ol 3, 4, 5-tri p h os p hate, 
PI( 3, 4, 5) P 3, a ke y si g nali n g m olec ul e i n v ol ve d i n t he re g ulati o n of a variet y of si g nal 
tra ns d ucti o n pat h wa ys. Base d o n t he cli nical a n d n o ncli nical data, it is pr o p ose d t hat acti vati o n 
of S HI P 1 ca n m o d ulate t he i nf la m mat or y pr ocess b y li miti n g i m m u ne cell acti vati o n, 
pr oi nfla m mat or y me diat or pr o d ucti o n a n d cell mi grati o n i n m ulti ple i m m u ne cell t y pes a n d ma y 
t heref ore pr o vi de a t her a pe utic be nefit i n t he treat me nt of C P/ C P P S  a n d ot her i nfla m mat or y 
diseases.  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 1  of 8 0  
 
T he i n vi v o a nti- i nfla m mat or y acti vit y of A Q X- 1 1 2 5 has bee n d e m o nstrate d i n n o ncli nical 
m o dels of i nfla m mat or y pai n i ncl u di n g a carra gee na n-i n d uce d m o del of c hr o ni c 
pr ostatitis/c hr o nic pel vic pai n a n d a n ac ute m o del of c ycl o p h os p ha mi de-i n d uce d bla d der c ystitis. 
I n vitr o, A Q X- 1 1 2 5 ca n r e d uce mast cell de gra n ulati o n, i m m u ne cell c he m ota xis a n d pr o-
i nfla m mat or y m e diat or r elease. T a ke n t o get her, t hese data s u p p ort t he p ote ntial effecti ve ness of 
A Q X - 1 1 2 5 i n treati n g c o n diti o ns i n v ol vi n g pai n a n d i nfla m mati o n.  
4. 2. 1  
N o ncli nic al St u dies  
T he ke y fi n di n gs fr o m t h e n o ncli nical st u dies were: 
•  A Q X - 1 1 2 5 e x hi bite d d ose- de pe n d e nt p har m ac ol o gic effects i n vitr o, i ncl u di n g acti vati o n 
o f rec o m bi na nt h u ma n S HI P 1 a n d re d u cti o n of p h os p h or ylat e d pr otei n-seri ne/t hre o ni ne 
ki nase acti vate d b y p h os p hati d yli n osit ol 3, 4, 5-tri p h os p hate, PI( 3, 4, 5) P 3 ( A kt) at seri ne 
4 7 3 ( p A kt [ S 4 7 3]) i n p h os p h oi n ositi de- 3- ki nase -acti vate d h u ma n T-cells. F u ncti o nall y, 
A Q X - 1 1 2 5 i n hi bite d c he m ota xis i n h u ma n le u k oc yt e s u bsets. 
•  I n s afet y p har mac ol o g y st u dies, A Q X- 1 1 2 5 pr o d u ce d a n o n-st atisticall y si g nifica nt 
tra nsie nt decr eas e i n ar o usal a n d l oc o m ot or acti vit y i n t he rat ce ntral ner v o us s yste m 
st u d y. A Q X- 1 1 2 5 i n hi bite d t he h u ma n Et her-a-g o -g o -Relate d G e ne p otassi u m c urre nt at 
a half ma xi mal i n hi bit or y c o nce ntrati o n  of 1 8 8. 9 μ M or 6 0, 7 3 1 n g/ m L, w hi c h is 
a p pr o xi matel y 2 8-f ol d hi g her t ha n t he h u ma n e x p os ure re p orte d at t he hi g h est cli nical 
d ose t o date of 5 4 2 m g. Fi nall y, t here were n o bi ol o gicall y si g nifica nt car di o vasc ular 
effects i n d o gs or res pir at or y effects i n rats.  
•  I n vitr o assa ys i n dicate d t hat per mea bilit y gl yc o pr otei n ( P-g p) a n d breast ca ncer 
resista nce pr otei n ( B C R P) are i n v ol ve d i n t he acti ve tra ns p ort of A Q X- 1 1 2 5, but A Q X -
1 1 2 5 is n ot a n i n hi bit or of P- g p, B C R P , or a n y ot her c o m m o n dr u g tra ns p orters e val uat e d 
at cli nicall y rele v a nt c o n ce ntrati o ns.  
•  A Q X - 1 1 2 5 w as rea dil y bi oa vaila ble a n d ra pi dl y a bs or be d wit h a mea n t er mi nal  
eli mi nati o n half -life (t1/ 2) of a p pr o xi matel y 6 h o urs i n t he rat a n d 9 h o urs i n t he d o g. 
E x p os ures were ge n erall y d ose - pr o p orti o nal or greater t ha n d os e pr o p orti o nal i n t he rat, 
a n d d ose- pr o p orti o nal or less t ha n d ose- pr o p orti o n al i n t he d o g, d e pe n di n g o n t he 
d urati o n of d osi n g. Acc u m ulati o n rati os s h o we d hi g her e x p os ures f oll o wi n g m ulti ple 
da ys of d osi n g c o m par e d wit h si n gle d oses. 
•  I n vitr o bi n di n g t o plas ma pr otei ns fr o m m o use, rats, d o gs, ra b bits, m o n ke ys, a n d h u m a ns 
ra n ge d fr o m 2 6 t o 5 2 %, a n d pr otei n bi n di n g t o h u ma n ser u m al b u mi n was 3 8 %. I n t he 
m o use, t he hi g hest c o nce ntrati o ns of A Q X- 1 1 2 5 (e x cl u di n g t he e x cret or y or ga ns) w ere 
o bser ve d i n t he l u n g, t h yr oi d, a n d a dre nal gla n ds, a n d t he l o west c o nce ntrati o n was 
o bser ve d i n t he br ai n. F oll o wi n g i ntra ve n o us ( I V) a d mi nistrati o n of [1 4C] - A Q X - 1 1 2 5 i n 
the al bi n o rat, t he hi g hest c o nce ntrati o ns (e x cl u di n g t he e x cret or y or ga ns) w ere i n t he 
c h or oi d ple x us, se mi nal vesicles, pa ncreas, st o mac h gastric m uc osa, a n d pit uitar y gla n d, 
a n d t he l o west c o nce ntrati o n was o bser ve d i n t he brai n. F oll o wi n g oral a d mi nistr ati o n of 
[1 4C] -A Q X - 1 1 2 5 i n partiall y pi g me nte d rats, t he hi g hest c o n ce ntrati o ns (e x cl u di n g t he 
e x cret or y or ga ns) wer e o bser ve d i n t he u veal tract, pit uitar y gla n d, pa n creas, har deria n 
gla n d, e x - or bital lac hr y m al gla n d a n d st o mac h m u c osa a n d t he l o w est c o nce ntrati o n was 
o bser ve d i n t he br ai n, s pi nal c or d a n d o c ular le ns. A Q X - 1 1 2 5 acc u m ulate d i n t he testes 
u p o n re peat e d d osi n g i n t he rat. I n a d diti o n, A Q X- 1 1 2 5 distri b ute d t o t he oc ular tiss ues i n 
t he rat (le ns a n d a q ue o us h u m o ur) a n d t he d o g (le ns, c or nea a n d a q u e o us h u m o ur) 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 2  of 8 0  
 
f oll o wi n g r e peat e d dail y d osi n g. Esti mate d oc ular le ns half-life of A Q X- 1 1 2 5 is 
a p pr o xi matel y 2 0 da ys i n t he rat a n d 7 t o 9 da ys i n t he d o g. 
•  T here w as n o si g nifica nt i n vitr o meta b olis m of A Q X- 1 1 2 5 wit h li ver micr os o mes of 
a ni mals a n d h u ma ns. I n t he rat, 5 meta b olites ( R 1- R 5) were i de ntifi e d i n t he plas ma, 
uri ne a n d f eces. I n t he d o g, 4 a d diti o nal meta b olites ( D 1- D 4) were i de ntifie d i n t he 
plas ma, uri ne a n d f eces. A Q X- 1 1 2 5 i n hi bite d C Y P 3 A 4/ 5 at t he e x pecte d i ntesti nal 
l u mi nal c o nce ntrati o ns f or a 2 0 0 m g d ose a n d i n d u ce d i n vitr o C Y P 3 A 4 m R N A 
e x pressi o n i n h u ma n he pat oc yt es. 
•  I n rats, [1 4C] -A Q X - 1 1 2 5 was e x crete d i n t he feces ( ~ 6 0 %) a n d uri ne ( ~ 3 0 %) f oll o wi n g 
oral a d mi nistrati o n a n d a b o ut e q uall y i nt o t he uri n e a n d feces f oll o wi n g I V 
a d mi nistrat i o n. I n d o gs [1 4C] -A Q X - 1 1 2 5 was e x crete d e q uall y i nt o t he uri n e a n d feces 
f oll o wi n g or al a d mi nistrati o n. Mass bala nce rec o v er y i n all st u dies was ≥9 0 %. 
•  T he ma xi m u m t olerate d d ose i n si n gle d ose t o xicit y st u dies was 5 0 0 m g/ k g i n t he m o use 
a n d 1 0 0 0 m g/ k g i n eac h of t he rat a n d d o g s p ecies.  
•  A series of re peat d ose t o xicit y st u dies i n t he rat h a ve bee n c o n d uct e d f or d urati o ns of 
7 da ys u p t o 2 6 w ee ks.  I n t he 2 6- wee k rat st u d y, t he n o o bser ve d a d verse effect le vel 
( N O A E L) was 3 0 m g/ k g/ da y, b ase d o n t he fi n di n gs i n fe males of bilateral p osteri or 
c ortical cataracts a n d micr osc o pic le ns s welli n g/cataracts, persiste nt estr o us c haracterize d 
b y t he i nterrelate d eff ects t o t he re pr o d ucti ve tract a n d ma m mar y gla n ds, a n d fi n di n gs i n 
males of re d u ce d ca u dal e pi di d y mal s per m de nsit y a n d c o u nts a n d e pi di d y mal e pit helial 
micr o vesic ular v ac u olati o n at 1 0 0 m g/ k g/ da y. At t he N O A E L, t he mea n m a xi m u m 
o bser ve d plas ma c o nce ntrati o n ( C ma x ) a n d area u n der t he plas ma c o nce ntrati o n– ti me 
c ur ve fr o m ti me 0 t o 2 4 h ( A U C 0- 2 4) val ues were 1 1 10 n g/ m L a n d 7 1 0 0 n g• hr/ m L, 
res pecti vel y, i n males a n d 1 5 8 0 n g/ m L a n d 9 9 4 0 n g•hr/ m L , res pecti vel y, i n fe males. 
•  A series of re peat d ose t o xicit y st u dies i n t he d o g ha ve bee n c o n d uct e d f or d urati o ns of 
1 0 da ys u p t o 3 9 w ee ks. I n t he 3 9- wee k d o g st u d y, dail y a d mi nistrati o n of A Q X - 1 1 2 5 at 
d ose le vels of 1 0, 3 0, a n d 5 0 m g/ k g/ da y res ulte d i n n o a d verse fi n di n gs. At t he N O A E L 
of 5 0 m g/ k g/ da y, t he mea n C ma x  a n d A U C 0- 2 4  val ues  were  6 1 6 0 n g/ m L a n d 
5 9, 3 0 0 n g• hr/ m L , r es pecti vel y, i n males a n d 6 8 2 0 n g/ m L a n d 6 9, 3 0 0 n g •hr/ m L , 
res pecti vel y, i n f e males.  
•  N o m uta ge nic p ote ntial was o bser v e d f or A Q X- 1 1 2 5 i n t he bacterial m utati o n, 
c hr o m os o me a berrati o n, or rat micr o n ucl e us tests. 
•  A Q X - 1 1 2 5 ha d n o eff ect o n rat male or fe male fertilit y or o n earl y e m br y o nic 
de vel o p me nt at d oses u p t o t he hi g hest d ose teste d of 3 0 0 m g/ k g/ da y. 
•  A Q X - 1 1 2 5 w as terat o ge nic i n rats, b ut n ot i n ra b bits. T he rat e m br y o-fetal de vel o p me nt 
N O A E L was 3 0 m g/ k g/ d a y ( Cma x  4 3 9 n g/ m L; A U C0- 2 4 4, 7 1 0 n g•hr/ m L)  b ase d o n 
terat o ge nic eff ects (e xter nal, s oft tiss ue a n d s kelet al malf or mati o ns a n d variati o ns a n d 
dela ys i n s k eletal ossificati o ns) o bser ve d at d oses ≥1 0 0 m g/ k g/ d a y. I n ra b bits, A Q X- 1 1 2 5 
was n ot terat o ge ni c at t he hi g hest d ose teste d of 8 0 m g/ k g/ da y ( Cma x  1 6, 0 0 0 n g/ m L; 
A U C 0- 2 4 7 8, 7 0 0 n g• hr/ m L).  
•  A Q X - 1 1 2 5 ca use d r e d uce d p u p via bilit y at d oses ≥7 5 m g/ k g/ d a y i ncl u di n g i ncreas es i n 
da ms wit h n o li ve b or n p u ps ( 1 5 0 m g/ k g/ da y), p u ps d yi n g wit hi n t he first 4 da ys after 
birt h a n d still b or n p u ps. T he deat hs occ urri n g i n t he late sta ge of gestati o n/s h ortl y aft er 
part uriti o n was s u g gesti ve of stress a n d/ or p h ysi ol o gical c ha n ges ass ociate d wit h t he late 
sta ge of pre g n a nc y. At 7 5 m g/ k g/ da y, t he F 0 da ms ha d b o d y wei g ht l oss i n lactati o n da ys 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 3  of 8 0  
 
( D L) 1 t o 4 a n d r e d uce d f o o d c o ns u m pti o n t hr o u g h o ut t he lactati o n peri o d ( D L 1 t o 1 4). 
Base d o n t h ese r es ults, t he mater nal N O A E L, de v el o p me ntal N O A E L a n d N O A E L f or 
gr o wt h a n d re pr o d ucti o n i n t he F 1 ge nerati o n i n male a n d fe male rats was 3 0 m g/ k g/ da y 
( Cma x  4 6 9 n g/ m L a n d A U C0- 2 4 4, 5 2 0 n g•hr/ m L) . 
•  A Q X - 1 1 2 5 w as distri b ute d fr o m mater n al circ ul ati o n t o fetal circ ulati o n i n pre g na nt rats 
wit h fetal plas ma le vels a p pr o xi matel y e q ual t o mater nal plas ma le v els.  
•  N o eff ects o n bl o o d, s plee n, b o ne marr o w, or l y m p h n o des were o bser v e d i n t he m o use. 
I n a m o use Stre pt oc occ us p ne u m o ni ae  h ost-resist a nce m o del, A Q X- 1 1 2 5 di d n ot c ha n ge 
t he ma g nit u de of p ost-i nf ecti o n Stre pt oc occ us p n e u m o ni ae  T y pe 1 4 titers i n t he l u n g or 
t he rate of b acterial clear a nce fr o m t he l u n g, w he n c o m pare d t o t he v e hicle c o ntr ol gr o u p. 
Refer t o t he A Q X - 1 1 2 5 I n vesti gat or’s Br oc h ure (I B) f or a d diti o nal details. 
4. 2. 2  
Cli nic al E x perie nce  
A t otal of 7 cli nical st u dies of A Q X - 1 1 2 5 ha ve b ee n c o m plete d. T hree w ere st u dies i n healt h y 
n or mal v ol u nteers ( A Q X- 1 1 2 5- 1 0 0, A Q X- 1 1 2 5- 1 0 1, a n d A Q X- 1 1 2 5- 1 0 2), i n w hic h safet y, 
t olera bilit y, p har mac o ki n etics , f o o d effects, cell ular a n d bi oc h e mical c h a n ges i n s p ut u m , a n d 
bi oe q ui vale nce of A Q X- 1 1 2 5 i m me diate releas e ta blets a n d ca ps ul es  were assesse d. Si n gle -
asce n di n g d oses of A Q X- 1 1 2 5 ra n ge d fr o m 1 7 m g t o 5 4 2 m g. M ulti ple-as ce n di n g d oses ra n ge d 
fr o m 1 0 0 m g t o 5 4 2 m g . 
O ne st u d y eac h was c o n d ucte d i n s u bjects wit h mil d at o pic ast h ma ( A Q X- 1 1 2 5- 2 0 0), i nterstitial 
c ystitis/ bla d der pai n  s y n dr o me (I C/ B P S, A Q X- 1 1 2 5- 2 0 1), c hr o ni c o bstr ucti ve p ul m o nar y disease 
(C O P D, A Q X - 1 1 2 5- 2 0 2), a n d at o pic der m ati tis (A D , A Q X - 1 1 2 5- 2 0 4). 
4. 2. 2. 1  
He alt h y V ol u nteer St u dies  
F oll o wi n g a d mi nistrati o n of a si n gl e oral d ose b y ca ps ule (si n gle as ce n di n g d ose), A Q X- 1 1 2 5 
was ra pi dl y a bs or b e d wit h a me dia n ti me t o reac h ma xi m u m c o nce ntrati o n ( Tma x ) ra n gi n g fr o m 
1. 0 t o 1. 5 h o urs p ost d ose. Plas ma dr u g c o nce ntrati o n s u bse q ue ntl y decli ne d sl o wl y i n a l o g-
li near fas hi o n wit h a t1/ 2 ra n gi n g fr o m 1 9. 5 t o 2 2. 4 h o urs. Mea n t1/ 2 was i n de pe n de nt of d ose. 
Fr o m 1 7 m g t o 5 4 2 m g, plas ma e x p os ure i ncrease d i n a d ose pr o p orti o nal ma n ner ( A U C0- ∞) or a 
slig htl y hi g her t ha n d ose pr o p orti o nal  ma n ner ( C ma x ). 
F oll o wi n g re peate d o nce dail y d osi n g f or u p t o 1 0 da ys ( 1 0 0 m g t o 5 4 2 m g), stea d y st ate tr o u g h 
plas ma c o nce ntrati o ns ( mea n c o nce ntrati o n 2 4 h o urs p ost d ose ) of A Q X-1 1 2 5 were reac he d at 
~ 5 t o 7 da ys. A Q X- 1 1 2 5 was ra pi dl y a bs or b e d wit h me dia n T ma x  reac he d b y 1. 0 t o 2. 0 h o urs. 
Plas ma dr u g c o nce ntr ati o n s u bse q ue ntl y d ecli ne d sl o wl y i n a l o g-li near fas hi o n wit h a t 1/ 2 
ra n gi n g fr o m 1 9. 3 t o 2 1. 1 h o urs. Fr o m 1 0 0 m g t o 5 4 2 m g, plas ma e x p os ure para meters i ncr ease d 
i n, or near, a d ose pr o p orti o nal ma n ner a n d mea n t1/ 2 was i n de pe n de nt of d ose. Plas ma A U C0- 2 4 
val ues i ncrease d at stea d y state c o m pare d t o si n gl e  d ose, i n dicati n g plas ma acc u m ulati o n u p o n 
re peat e d d osi n g i n dicati n g c o n ce ntr ati o ns ~ 5 0 % hi g her t ha n f oll o wi n g a si n gle d ose. 
T he eff ect of f o o d o n t he plas ma p har mac o ki netics of A Q X -1 1 2 5 was t o i ncrease i n t he m e dia n 
T ma x  fr o m 1 t o 4 h o urs. T he a bs or pti o n of a si n gle 2 0 0 m g d ose of A Q X- 1 1 2 5 was n ot altere d b y 
f o o d. 
T here w ere n o d eat hs, seri o us A Es (S A E s), la b orat or y treat me nt e mer ge nt a d verse e ve nts 
(T E A Es ), or s u bject disc o nti n uati o ns d ue t o T E A Es re p orte d d uri n g t hes e st u dies. 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 4  of 8 0  
 
4. 2. 2. 2  
Ast h m a St u d y  
O ne st u d y was c o n d u cte d i n s u bjects wit h mil d at o pic ast h ma ( A Q X- 1 1 2 5- 2 0 0), i n w hic h t he 
late ast h matic res p o ns e ( LA R) t o i n hale d aller ge n c halle n ge w as assess e d. A Q X - 1 1 2 5 d osi n g 
was 4 5 0 m g.  Ster oi d-naï ve male a n d f e male ast h matics were assesse d f or L A R  f oll o wi n g i n hale d 
aller ge n c h alle n ge. A si g nifica nt, 2 0 % i m pr o ve me nt i n t he A U C 4- 1 0 of L A R was de m o nstrate d 
wit h 4 5 0 m g A Q X - 1 1 2 5 as c o m par e d wit h  place b o ( P = 0. 0 2 7). T h ere were n o deat hs, S A Es, or 
s u bject disc o nti n uati o ns d ue t o T E A Es i n t his st u d y. 
4. 2. 2. 3  
I nterstiti al C ystitis/ Bl a d der P ai n S y n dr o me, C hr o nic O bstr ucti ve P ul m o n ar y 
Dise ase, a n d At o pic Der m atitis St u dies  
O nce dail y  or al d osi n g wit h 2 0 0 m g A Q X- 1 1 2 5 h as bee n st u die d i n 3 P has e 2 trials: f or 6 wee ks 
i n s u bjects wit h I C/ B P S, a n d 1 2 wee ks i n s u bjects wit h C O P D  or A D .  
I n t he P h ase 2 I C/ B P S st u d y, or al A Q X - 1 1 2 5 2 0 0 m g o nce dail y f or 6 w ee ks re d uce d m a xi m u m 
pel vic pai n, v oi di n g fre q ue nc y a n d ot her uri nar y s y m pt o ms (as meas ure d b y t he O’ Lear y- Sa nt 
I nterstitial C ystitis S y m pt o m a n d Pr o ble m Q uesti o n naire a n d t he Bla d d er Pai n/I nterstitial 
C ystitis S y m pt o m Sc ore ) i n 6 9 w o me n wit h m o derate t o se vere I C/ B P S. M ore pr o gra ms f or t his 
i n dicati o n are pla n n e d i n t he f ut ure. 
A Q X - 1 1 2 5 di d n ot ha ve a treat me nt effect o n rec urre nt e x acer bati o ns i n s u bjects wit h C O P D 
f oll o wi n g a rece nt e x acer bati o n or o n A D si g ns a n d s y m pt o ms i n s u bjects wit h mil d t o m o derate 
A D i n P hase 2 cli nical tri als. T here f ore, t here are c urre ntl y n o pla ns t o de vel o p A Q X- 1 1 2 5 f or 
C O P D or A D.  
Acr oss all t he P hase 2 st u dies, t he perce nta ge of A Q X - 1 1 2 5 s u bjects w h o e x perie nce d a n y 
T E A E ( 5 6 % o v erall) w as si milar t o t he perce nta ge i n place b o ( 5 5 % o v erall), a n d i n t he 6 wee k 
Lea ders hi p st u d y of I C/ B P S patie nts, was l o wer i n A Q X- 1 1 2 5 ( 6 0 %) t ha n place b o ( 7 8 %). 
A Es of i nterest i ncl u de G astr oi ntesti nal ( GI ) Dis or ders, si nce t he mai n t y pe of A E  i n P hase 1 
safet y st u dies were mil d n o n-seri o us GI Dis or d ers, w hic h occ urre d at great er t ha n 2-f ol d 
i nci de nce f oll o wi n g tr eat me nt wit h 4 5 0 m g  t o 5 4 2 m g A Q X- 1 1 2 5 c o m pare d t o place b o. I n t he 
P hase 2 st u dies, wit h a o nce dail y 2 0 0 m g d ose of A Q X- 1 1 2 5 o ver 6 or 1 2 wee ks, t he i nci de n ce 
of GI Dis or ders was 2 1 % i n A Q X- 1 1 2 5 s u bjects c o m pare d wit h 1 6 % of place b o s u bjects. As 
wit h t he P hase 1 st u dies i n healt h y s u bjects, t he GI Dis or ders were ge nerall y mil d a n d t olera bl e. 
E ye Dis or ders are a n ot her A E  cat e g or y of i nterest base d o n t he fi n di n gs of n o ncli nical st u dies. I n 
t hese P hase 2 cli nical st u dies, t he o verall i nci de n ce of E ye Dis or d ers w as l o wer i n A Q X- 1 1 2 5 
s u bjects ( 7 %) c o m pare d wit h place b o s u bjects ( 1 0 %).  
T he fre q u e nc y of S A Es was l o wer i n s u bjects treate d wit h A Q X- 1 1 2 5 ( 5 %) as c o m pare d wit h 
place b o ( 7 %), i ncl u di n g 1 deat h i n eac h gr o u p ( 0. 4 % eac h). T hes e t y p es of e ve nts were o bser v e d 
o nl y i n s u bjects wit h C O P D, w h o ha d se vere u n derl yi n g diseas e, a n d w ere n ot relate d t o t he 
st u d y treat me nts. 
St u d y treat me nt disc o nti n uati o ns d ue t o T E A Es occ urre d i n 6 % of s u bjects treate d wit h 
A Q X - 1 1 2 5 a n d 5 % of pl ace b o s u bjects, m ost of w hic h were c o nsi dere d u nrelate d t o t he st u d y 
treat me nt. T her e were m ore disc o nti n uati o ns d ue t o T E A Es i n t he 1 2-wee k st u dies of s u bjects 
wit h C O P D a n d A D t ha n i n t he 6- wee k st u d y of I C/ B P S. T his is relate d t o t he relati vel y p o or 
hea lt h of t he C O P D s u bjects st u die d, b ut t he l o n ger d urati o n of treat me nt a n d f oll o w- u p c o ul d 
als o be a f act or.  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 5  of 8 0  
 
T a ble 2 . A Q X -1 1 2 5 S afet y acr oss  P h ase 2 Tri als ( at Le ast 6 Wee ks of D osi n g)  
 
6 w ee ks o f d osi n g 
I C/ B P Sa 
1 2 w ee ks of d osi n g  
C O P D b  + A D c 
O ver all  
( all P h ase 2 co m bi ne d)  
Pl ace b o 
N = 3 2  
A Q X - 1 1 2 5 
N = 3 7  
Pl ace b o 
N = 2 2 8  
A Q X -1 1 2 5 
N = 2 2 6  
Pl ace b o 
N = 2 6 0  
A Q X -1 1 2 5 
N = 2 6 3  
A n y T E A E, n ( %)  
2 5 ( 7 8)  
2 2 d ( 6 0) 
1 1 8 ( 5 2)  
1 2 6 ( 5 6)  
1 4 3 ( 5 5)  
1 4 8 ( 5 6)  
GI Dis or ders e 
1 1 ( 3 4)  
1 1 ( 3 0)  
3 1 ( 1 4)  
4 3 ( 1 9)  
4 2 ( 1 6)  
5 4 ( 2 1)  
E ye Dis or ders f 
3 ( 9)  
2 ( 5)  
2 2 ( 1 0)  
1 6 ( 7)  
2 5 ( 1 0)  
1 8 ( 7)  
S A Es, n ( %)  
0 ( 0)  
0 ( 0)  
1 8 ( 8)  
1 2 ( 5)  
1 8 ( 7)  
1 2 ( 5)  
Deat h  
0 ( 0)  
0 ( 0)  
1 ( 0. 4)  
1 ( 0. 4)  
1 ( 0. 4)  
1 ( 0. 4)  
T E A Es lea di n g t o  
disc o nti n uati o n, n ( %)  
1 ( 3)  
2 ( 5)  
1 1 ( 5)  
1 3 ( 6)  
1 2 ( 5)  
1 5 ( 6)  
A b bre viati o ns: A D =at o pic der matitis; C O P D =c hr o nic o bstr ucti ve p ul m o nar y disease; GI = gastr oi ntesti nal; 
I C/ B P S =i nterstitial c ystitis/ bla d der pai n s y n dr o me; S A E =seri o us a d verse e ve nt; T E A E =treat me nt e mer ge nt a d verse 
e ve nt  
a L E A D E R S HI P St u d y ( A Q X -1 1 2 5 -2 0 1) i n  I C/ B P S 
b F L A G S HI P St u d y ( A Q X -1 1 2 5 -2 0 2) i n C O P D  
c KI N S HI P St u d y ( A Q X -1 1 2 5 -2 0 4) i n A D  
d T E A Es s h o w n are t h ose re p orte d fr o m t he start of d osi n g t hr o u g h t o t he e n d of t he W ee k  1 0 f oll o w -u p  
e GI Dis or ders Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A ) S yste m Or ga n Class  
f E ye Dis or ders Me d D R A S yste m Or ga n Class  
 
T he safet y pr ofile of A Q X - 1 1 2 5 was als o re vie w e d i n t he c o nte xt of ge n der. W hile t he 
Lea ders hi p st u d y of I C/ B P S o nl y i ncl u de d fe male s u bjects, a p pr o xi matel y half of t he s u bjects i n 
t he ot her P hase 2 st u dies were mal e. T here was n o differe n ce i n t he i nci d e n ce of T E A Es bet wee n 
A Q X - 1 1 2 5 a n d pl ace b o i n t he s u bsets of male s u bjects ( 4 8 % f or eac h treat me nt; St u dies A Q X -
1 1 2 5- 2 0 2 a n d A Q X- 1 1 2 5- 2 0 4 c o m bi ne d data ) or fe male s u bjects ( 6 2 % wit h A Q X- 1 1 2 5 a n d 
6 1 % wit h place b o; St u dies A Q X - 1 1 2 5- 2 0 2 a n d A Q X- 1 1 2 5- 2 0 4 c o m bi ne d data ). 
Refer t o t he A Q X - 1 1 2 5 I B f or a d diti o nal details. 
5  
T RI A L O B J E C TI V E S  
5. 1  
Pri m ar y  O bjecti ve  
T he pri mar y o bjecti ve of t his st u d y is t o e val u ate t he effect of 1 2 w ee ks of treat me nt wit h 
A Q X - 1 1 2 5 ( 2 0 0 m g) a d mi nistere d orall y o n ce- dail y c o m pare d t o place b o o n t he c ha n ge fr o m 
Baseli ne  (Visit  2) t o Wee k  1 2 (Visit  4) i n ma xi m u m dail y pel vic p ai n ( mea n) i n male s u bjects 
wit h n o n- bacteri al C P/ C P P S usi n g a sta n dar dize d 1 1 - p oi nt N u merical Rati n g Scal e (N R S ) pai n 
sc ore r ec or d e d dail y b y a n electr o nic diar y (e Diar y). 
5. 2  
Sec o n d ar y O bjecti ves  
T he sec o n d ar y o bjecti ves of t his st u d y are t o e val u ate:  
•  T he eff ects of 1 2 w ee ks of treat me nt wit h A Q X- 1 1 2 5 ( 2 0 0 m g) a d mi nistere d orall y o nce-
dail y c o m p are d t o place b o o n t he c ha n ge fr o m Baseli ne  (Visit  2) t o Wee k  1 2 (Visit  4) f or 
eac h of t h e f oll o wi n g: 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 6  of 8 0  
 
o  N I H C hr o nic Pr ostatitis S y m pt o m I n d e x ( NI H -C P SI ) pai n s u bscale a n d all d o mai ns 
t otal sc ore 
o  Male se x ual healt h as meas ure d usi n g t he I nter nati o nal I n d e x of Erectile F u ncti o n 
Q uesti o n naire, Er ectile F u ncti o n D o mai n ( II E F-E F ) 
o  A vera ge dail y pel vic pai n (e Diar y), a vera ge a n d ma xi m u m pel vic pai n ( Pa per- b ase d 
N R S, i n cli nic), usi n g t he sta n dar dize d 1 1- p oi nt N R S 
o  2 4- h o ur v oi di n g fre q u e nc y (e Diar y) 
•  Ti me c o urse of eff ects:  A Q X - 1 1 2 5 ( 2 0 0 m g) c o m pare d t o place b o o n t he c h a n ge fr o m 
Baseli ne  ( Visit 2) at Wee k  6 (Visit  3), Wee k  1 2 (Visit  4), a n d Wee k  1 6 (i.e. 4 wee ks after 
e n d of treat me nt) f or eac h of t he pai n a n d s y m pt o m scale e n d p oi nts 
•  T he o ver all res p o nse t o tr eat me nt  f or A Q X- 1 1 2 5 ( 2 0 0 m g) c o m pare d t o place b o as 
meas ure d b y t he s u bject’s Gl o b al Res p o nse Assess me nt (G R A ), Patie nt’s Gl o bal 
I m pr essi o n of C ha n ge s cale (P GI - C) a n d Patie nt’s Gl o bal I m pressi o n of Se verit y s cale 
(P GI - S) at W ee k 1 2 (Visit  4) 
•  T he pr o p orti o n of s u bjects wit h ≥3 0 % a n d ≥5 0 % i m pr o ve me nt i n ma xi m u m dail y pel vic 
pai n  ( mea n) usi n g t he 1 1- p oi nt N R S rec or de d b y e D iar y a n d t h e NI H - C P SI p ai n s u bscale 
c o m pare d t o place b o, at Wee k s 6 ( Visit 3) a n d 1 2 ( Visit 4) 
•  Res p o n der a n al ysis: r es p o nse t o treat me nt defi n e d b y a n y of t he f oll o wi n g:  
o  Decr ease i n ma xi m u m dail y pel vic pai n fr o m Baseli ne t o Wee k 1 2 (e Diar y) wit h 
n o c ha n ge i n t he a m o u nt or stre n gt h of c o n c o mita nt a nal gesic me dicati o ns 
o  Decr ease i n ma xi m u m dail y pel vic pai n fr o m Baseli ne t o Wee k 1 2 (e Diar y) wit h 
a decr eas e i n t he a m o u nt or stre n gt h of c o n c o mita nt a nal gesic me dicati o ns  
•  Disc o nti n uati o n of st u d y me dicati o n d ue t o treat m e nt fail ure ( % meeti n g treat me nt fail ure 
criteria a n d ti me t o e ve nt) 
5. 3  
S af et y  O bjecti ves  
T he safet y o bjecti ves of t his st u d y ar e t o e val uate:  
•  Safet y a n d t oler a bilit y of A Q X - 1 1 2 5 ( 2 0 0 m g) c o m pare d t o place b o d uri n g t he 1 2- wee k  
treat me nt peri o d 
•  Oc ular safet y bas e d u p o n assess me nt of le ntic ular o pacificati o n usi n g Le ns O pacificati o n 
Classificati o n S yst e m  (L O C S ) III, best c orrecte d  vis ual ac uit y ( B C V A) usi n g t he 
L o garit h m of t he Mi ni m u m A n gle of Res ol uti o n  (L o g M A R)  c hart, intra o c ular p ress ure 
(I O P), c or n eal stai ni n g, a n d slit la m p e x a mi nati o n 
6  
I N V E S TI G A TI O N A L P L A N 
6. 1  
O ver all Tri al Desi g n a n d Pl a n: Descri pti o n  
I n t his d o u ble- bli n d, place b o-c o ntr olle d st u d y, a p pr o xi matel y 1 0 0 mal e s u bjects dia g n ose d wit h 
C P/ C P P S will be r a n d o mize d t o eit her A Q X- 1 1 2 5 ( 2 0 0 m g) or place b o i n a 1: 1 rati o acr oss 
a p pr o xi matel y 3 0 ce nt ers i n N ort h A merica. T h e st u d y will c o nsist of a scree ni n g peri o d of u p t o 
3 wee ks , a 1 2 - wee k treat me nt peri o d f oll o we d b y a 4-wee k O ff- Treat me nt Safet y F oll o w - u p 
peri o d, a n d a n O p ht hal mic Safet y F oll o w- u p Visit 6  m o nt hs p ost last d ose, f or a t otal st u d y 
d urati o n of a b o ut 4 1 wee ks. T here will als o be a f oll o w- u p tele p h o ne call 3 m o nt hs after t he last 
d ose.  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 7  of 8 0  
 
At Scree ni n g Visit 1, eac h s u bject will c o m plete a set of q uesti o n naires, a n d recei v e (a n d b e 
trai ne d t o use) a n e Diar y. S u bjects will rec or d t heir a vera ge a n d ma xi m u m dail y pel vic p ai n 
sc ore, at a p pr o xi matel y t he sa me ti me eac h da y (i n t he e ve ni n g pri or t o t he last d ose of pai n 
me dicati o n), as w ell as t heir dail y us e of a n al gesic pai n me dicati o ns. Baseli ne o p ht hal mic 
assess me nts, i ncl u di n g le ntic ular o pacificati o n ass ess me nt usi n g L O C S III, ca n be c o m plete d as 
a se par ate visit a n y ti me d uri n g t he s cree ni n g p eri o d (a n y ti me bef o re Visit 2).  
At Baseli ne ( Visit 2), all s u bjects will ret ur n t o t he cli nic f or re vi e w of eli gi bilit y a n d t o c o m plete 
t he efficac y q u esti o n nair es a n d assess me nts t o est a blis h Baseli ne v al ues. A vera ge d ail y p el vic 
pai n sc ores r ec or d e d i n t he e Diar y wit hi n the 7 da ys pri or t o Bas eli ne ( Visit 2) will be part of t he 
st u d y e ntr y criteria. If all e ntr y criteri a are met, t he s u bject will be ra n d o mize d ( 1: 1) t o recei ve a 
si n gle dail y or al d ose of 2 ta blets f or 1 2 wee ks as f oll o ws:  
•  A Q X - 1 1 2 5 2 0 0 m g d ose gr o u p: 2 A Q X- 1 1 2 5 1 0 0 m g ta blets; or,  
•  Place b o gr o u p: 2 place b o ta blets 
All e nr olle d s u bjects will rec or d t h e f oll o wi n g i n t he e Diar y (fr o m Scree ni n g Visit 1 t o Wee k 1 6 
[Off -Treat me nt Safet y F oll o w - u p Visit]): 
•  Ma xi m u m dail y pel vic p ai n: s u bjects will assess t heir ma xi m u m pel vic pai n f or t hat da y 
o n a scale of 0 t o 1 0, wit h 0 i n dicati n g ‘ n o p el vic pai n’ a n d 1 0 i n dicati n g ‘ pel vic pai n as 
ba d as y o u ca n i ma gi n e’  
•  A vera ge dail y pel vic pai n. S u bjects will assess t heir a vera ge p el vic pai n f or t hat da y o n a 
scale of 0 t o 1 0, wit h 0 i n dicati n g ' n o p el vic pai n' a n d 1 0 i n dicati n g ' pel vic p ai n as ba d as 
y o u ca n i ma gi ne' 
•  A nal gesic me dicati o n ta ke n eac h da y  
•  2 4- h o ur v oi di n g fre q u e nc y: v oi di n g fre q u e nc y will be meas ure d o ver a 2 4- h o ur peri o d, 
wit hi n a 3 - da y ( 7 2 h o urs) wi n d o w bef ore t he ne xt sc he d ule d visit ( Visit 2, 3, 4 a n d Off-
Treat me nt Saf et y F oll o w - u p Visit ) 
At Wee k 6 ( Visit 3) , Wee k 1 2 ( Visit 4) a n d Wee k 1 6 (Off -Treat me nt Safet y F oll o w - u p Visit), 
d uri n g t he cli nic visit, s u bjects will c o m plete NI H - C P SI, pa per- bas e d 1 1- p oi nt N R S (a vera ge a n d 
ma xi m u m pel vic pai n e x perie nce d o ver t h e last 2 4 h o urs), G R A, P GI- C, II E F, P GI -S,  P H Q - 9, 
ha ve vital si g ns assesse d, a n d ret ur n u n us e d st u d y dr u g ( Wee k 6 a n d 1 2). A n y a d v erse e ve nts 
( A Es) are t o be r ec or d e d. 
S u bject c o m plia nce wit h t he e Diar y will  be m o nit ore d b y trai ne d st u d y site pers o n nel at eac h 
st u d y visit. 
All s u bjects c o m pleti n g t he 1 2 wee ks of treat me nt ( Visit 4) will be c o nsi dere d c o m pleters of 
treat me nt. S u bjects w h o wit h dra w fr o m t he st u d y d uri n g t he treat me nt peri o d s h o ul d c o m plete a n 
Earl y Ter mi nati o n Visit. S u bjects w h o disc o nti n ue t he d o u ble- bli n d treat me nt f or a n y reas o n will 
be e nc o ur a ge d t o c o nti n u e wit h all s u bse q ue nt st u d y-relate d visits a n d e v al uati o ns, wit h 
e m p hasis o n o btai ni n g pel vic pai n data, a nal gesic me dicati o n data a n d v oi di n g fre q ue n c y data t o 
assess effi cac y e n d p oi nts. S u bjects w h o c o m plete t he st u d y or earl y ter mi nate d uri n g t he st u d y 
will be as ke d t o ret ur n f or t he Safet y F oll o w- u p Visit 4  wee ks after disc o nti n ui n g st u d y dr u g, a n d 
t he O p ht hal mic Safet y F oll o w- u p Visit 6 m o nt hs after t he l ast d ose. S u bjects will als o be 
c o ntacte d via tel e p h o ne f or t he f oll o w- u p tele p h o n e call 3  m o nt hs after t h eir last d ose.  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 8  of 8 0  
 
6. 2  
Disc ussi o n of Tri al Desi g n I ncl u di n g t he C h oice of C o ntr ol Gr o u p  
T he r a n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, parallel - gr o u p d esi g n use d f or t his st u d y is 
t he c urr e nt sta n dar d f or i nter ve nti o nal h u ma n trials.  
7  
S E L E C TI O N O F S U B J E C T S 
A p pr o xi matel y 1 0 0 m ale s u bjects at a p pr o xi matel y 3 0 sites i n N ort h A merica  are pla n ne d.  
7. 1  
I ncl usi o n Criteri a 
F or i ncl usi o n i nt o t he scr ee ni n g peri o d s u bjects m ust meet t he f oll o wi n g criteria:  
1.  Pr o vi de writte n i nf or me d c o nse nt a n d t he willi n g n ess a n d a bilit y t o c o m pl y wit h all 
as pects of t he st u d y r e q uire me nts  
2.  Males, ≥1 8 a n d ≤8 0 years of a ge at S cree ni n g Visit  1 
3.  Ha ve pai n or disc o mf ort i n t he pel vic re gi o n f or at least 3 m o nt hs i n t he last 6 m o nt hs, i n 
t he a bse nce of a uri nar y tract i nfecti o n or ot her p el vic/ ur ol o gical ca us e, a n d ha ve a 
p h ysicia n dia g n osis of C P/ C P P S ( NI H Pr ostatitis , Cate g or y III)  
4.  NI H - C P SI of ≥1 5 o n t he t otal sc ore 
5.  S u bjects m ust a gree t o us e a c o n d o m f or se x ual i nterc o urs e fr o m S cree ni n g Visit  1 u ntil 
at least 9 0 da ys aft er t he l ast d ose of st u d y dr u g, u nless t he y h a ve bee n s ur gicall y 
sterilize d ( vasect o m y) f or a mi ni m u m of 6 m o nt hs. Tr ue a bsti ne nce fr o m s e x ual 
i nterc o urse i n acc or da nce wit h t he preferre d a n d us ual lifest yle of t he s u bject is als o 
acce pta ble  
6.  Ha ve a n a ver a ge d ail y p el vic pai n sc ore of ≥4 o ut of 1 0 o n t he 1 1- p oi nt N R S pai n scale 
( mea n of t he a ver a ge d ail y pel vic p ai n sc ore rec or de d at eac h of t he 7 d a ys pri or t o 
Baseli ne  [Visit  2]).  A mi ni m u m of 5 dail y rec or ds wit hi n 7 da ys pri or t o Baseli ne  (Visit  
2) m ust be rec or de d  
7.  M ust be ca pa ble of v oi di n g i n de p e n de ntl y f or 3 0 da ys pri or t o scree ni n g (t o all o w 
c o m pleti o n of 2 4- h o ur v oi di n g diar y) 
7. 2  
E xcl usi o n Cr iteri a 
S u bjects meeti n g a n y of t he f oll o wi n g criteria are i neli gi ble f or t he trial: 
1.  Dia g n osis of N I H Pr ostatitis Cate g ories I (ac ut e pr ostatitis) or II (c hr o ni c bacterial) 
p r ostatitis 
2.  Dia g n osis of I C/ B P S wit h s y m pt o ms of pai n, press ure, or disc o mf ort p erce i ve d t o be 
relate d t o t he bla d d er, a n d ass ociate d l o wer uri nar y s y m pt o ms f or > 6 w ee ks i n t he 
a bse nce of i nfecti o n or ot her i de ntifia ble ca uses 
3.  Relief of pel vic pai n after v oi di n g or h a ve > 1 5 v oi ds per da y  
4.  P ost- v oi d resi d ual v ol u me > 1 5 0 m L 
5.  Ha ve ha d a n u nres ol v e d ( p ositi ve bacterial uri ne c ult ure) uri nar y tract i nfecti o n  wit hi n 8 
wee ks (i ncl usi ve) pri or t o Scree ni n g Visit  1 (s u bjects ca n rescree n [ u p t o 1 ti me] o nce 
i nfecti o n clears)  
6.  Hist or y of pre vi o us pr ost ate or bla d der i nter ve nti o n ( i.e. pr ostate bi o ps y, c yst osc o p y, or 
i n d welli n g uri nar y cat h eter) wit hi n 1 m o nt h of Scree ni n g Visit  1, hist or y of micr o wa ve 
t hera p y, tra ns uret hral res ecti o n of t he pr ostate, tra ns uret hral ra di ofre q u e nc y 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 2 9  of 8 0  
 
t her m ot hera p y, tr a ns uret hral i ncisi o n of t he pr ostate, tra ns uret hral nee dle a blati o n, 
tra ns uret hr al laser v a p ori zati o n of t he pr ostate, Ur olift® , Rez u m, a n d ot her ur ol o gical 
i nter ve nti o ns (e. g., b ot uli n u m t o xi n) wit hi n 6 m o nt hs of Scree ni n g Visit  1  
7.  U nilateral testic ular or scr otal pai n as t he s ole s y m pt o m of C P / C P P S 
8.  O n g oi n g, s y m pt o matic uret hral strict ure disease  
9.  Catastr o p hizi n g pai n sc or e of ≥3 0 as deter mi ne d b y t he Pai n Catastr o p hizi n g Scal e ( P C S ) 
1 0.  C urre nt maj or de pr essi ve dis or der ( i.e. Patie nt H ealt h Q uesti o n naire - 9 [P H Q - 9] sc ore 
≥1 0) 
1 1.  Ne ur ol o gic diseas e or dis or der affecti n g t h e bla d d er, a bilit y t o v oi d s p o nta ne o usl y, or 
directl y c o ntri b uti n g t o uri nar y s y m pt o ms (e . g., m ulti ple scler osis, a ut o n o mic 
ne ur o pat h y) 
1 2.  Se vere, e x cr u ciati n g p ai n d uri n g rectal e x a m (i.e.  a n “i na bilit y t o perf or m t he e x a m”)  
1 3.  Hist or y of c hr o nic s u bsta nce a b use, d e pe n d e nc y or a b use of o pi oi ds, or ot h er narc otics 
wit hi n t he last 2  years  
1 4.  C urre ntl y recei vi n g , or e x pect t o recei ve , a n y of t he f oll o wi n g pr o hi bite d me dicati o ns or 
pr oce d ur es: 
o  N o n -ster oi d al a nti-i nfl a m m at or y dr u g or ot her me dic at i o n (e. g. al p h a-bl oc kers) 
f or C P/ C P P S, u nless o n a sta ble d ose f or ≥3 0 da ys pri or t o Scree ni n g Visit 1 
o  L o n g- acti n g o pi oi d s: wit hi n 2 wee ks pri or t o Bas eli ne ( Visit 2) or e x pecte d t o ta ke 
a n y l o n g-acti n g o pi oi d s at a n y ti me d uri n g t he st u d y  
o  S h ort - acti n g o pi oi d or o pi oi d-c o nt ai ni n g a n al gesics: m ore t ha n 1 0 d oses/ m o nt h, or 
m ore t ha n a si n gle d ose > 2 da ys per wee k, or a n y s h ort- acti n g o pi oi ds wit hi n 3 da ys 
pri or t o ra n d o mizati o n 
o  Or al ster oi d t her a p y, i m m u n os u p press a nts/i m m u n o m o d ul at ors  (i ncl u di n g dail y 
p h os p h o diesterase T y p e 4 i n hi bit ors) wit hi n 3 0 da ys pri or t o Scree ni n g Visit  1 a n d 
t hr o u g h o ut t he st u d y 
o  Ha ve ta k e n a n y i n vesti g ati o n al dr u g or de vice wit hi n 9 0 da ys pri or t o S cree ni n g 
V isit 1, or ha ve ha d pr e vi o us e x p os ure t o A Q X- 1 1 2 5 
1 5.  A n y p ri or hist or y of pel vic ca ncer (e . g., c ol orectal, ge nit o uri nar y) or treat m e nt (ra diati o n 
or c he m ot her a p y) t here of 
1 6.  Maj or s ur ger y wit hi n 3 m o nt hs pri or t o Scree ni n g Visit  1 
1 7.  Ha ve a n y ot h er c o n diti o n/ disease w hic h, i n t he o pi ni o n of t he I n vesti gat or , c o ul d 
c o m pr o mise s u bject s af et y or i nterfere wit h t he s u bject’s partici pati o n i n t h e st u d y or i n 
t he e val uati o n of t he st u d y r es ults. I n cas e of a n y d o u bt, t he I n v esti gat or s hall c o ns ult t he 
me dical m o nit or  
1 8.  K n o w n i nt olera nce t o micr o- cr ystalli ne cell ul ose ( A vicel ®  P H - 1 0 2), ma n nit ol or ot her 
i n gre di e nt of A Q X-1 1 2 5 ta blets  
7. 3  
Criteri a f or I n di vi d u al S u bject Disc o nti n u ati o n of St u d y Dr u g  
S u bjects s h o ul d be disc o nti n ue d fr o m st u d y dr u g , w hile e nc o ura ge d t o f oll o w all ot her pr ot oc ol-
s pecifie d pr o ce d ur es, f or t he f oll o wi n g reas o ns: 
•  N o nc o m pli a nce wit h trial or f oll o w - u p pr oce d ures t hat i n t he I n v esti gat or’s o pi ni o n 
w o ul d je o par dize t he s u bject’s safet y  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 0  of 8 0  
 
•  Disc o nti n u ati o n of st u d y dr u g at t he I n vesti gat or’s re q uest f or a n y reas o n t h at t he 
I n v esti gat or belie ves c o nti n uati o n of st u d y dr u g t h era p y w o ul d n ot be i n t he s u bject’s 
best i nterest   
•  S u bjects ma y disc o nti n ue st u d y dr u g  at a n y ti me f or dr u g i nt olera bilit y, dis ease 
pr o gressi o n, a vaila bilit y of ot her t hera pe utic o pti o ns, or s u bject j u d g me nt 
7. 4  
Criteri a f or I n di vi d u al S u bject Wit h dr a w al fr o m t he Tri al 
S u bjects ma y wit h dr a w fr o m f urt her p artici pati o n i n t he st u d y at a n y ti me a n d f or a n y reas o n 
wit h o ut prej u dice. T he d e gree t o w hi c h a s u bject wit h dra ws ca n v ar y a n d eff orts will be ma de t o 
c ollect i m p orta nt safet y d ata if feasi ble a n d t he s u bject c o nse nts. A s u bject will be c o nsi dere d t o 
be wit h dra w n fr o m t he trial f or t he f oll o wi n g reas o ns: 
•  Wit h dra w n c o nse nt fr o m all treat me nt a n d f oll o w- u p 
•  Deat h  
•  L ost t o f oll o w- u p 
•  Ter mi nati o n of t he trial b y t he S p o ns or 
A n y s u bject w h o is wit h dra w n s h o ul d c o m plete all Earl y Ter mi nati o n ( E T ) Visit  assess me nts .  
S u bjects will be as ke d t o ret ur n f or t h e Off - Treat me nt Safet y F oll o w - u p Visit 4 wee ks after 
disc o nti n ui n g st u d y dr u g, a n d t he O p ht hal mic Safet y F oll o w- u p Visit 6 m o nt hs after t he last 
d ose. S u bjects will als o be c o ntact e d via tele p h o ne f or t he f oll o w- u p tel e p h o ne call 3 m o nt hs 
after t heir l ast d ose.   
8  
T R E A T M E N T S  
8. 1  
A Q X - 1 1 2 5 T a blet Dr u g Pr o d uct  
A Q X - 1 1 2 5 ta blet dr u g pr o d uct is s u p plie d as r o u n d, w hite, bic o n ve x, fil m-c oate d ta blets 
c o ntai ni n g 1 0 0 m g A Q X- 1 1 2 5 (fr ee bas e) acti ve i n gre die nt a n d p har mace utical gra de e x ci pie nts.  
T he e x ci pie nts use d i n t he A Q X- 1 1 2 5 1 0 0 m g ta bl et d osa ge f or m are: micr ocr ystalli ne cell ul ose 
( A vicel®  P H - 1 0 2), ma n nit ol ( Pearlit ol®  5 0 C), s o di u m la ur yl s ulfat e, c oll oi dal silic o n di o xi de, 
cr os p o vi d o ne, ma g nesi u m stearate, a n d O pa dr y II W hite (c oati n g mi xt ure).  
T otal ta blet wei g ht will be a p pr o xi matel y 3 1 4 m g.  
F urt her d etails o n t he acti ve i n gr e die nt of A Q X- 1 1 2 5 are pr o vi d e d i n t he A Q X - 1 1 2 5 I B. 
8. 2  
Pl ace b o T a blet Dr u g Pr o d uct 
Matc hi n g place b o is i de ntical i n a p pear a nce t o t he test pr o d uct a n d c o ntai ns n o acti ve i n gre die nt. 
Place b o ta blet dr u g pr o d uct is s u p plie d as wei g ht a n d a p peara n ce matc h e d ta blets wit h t he acti ve 
i n gre di e nt c o m p o ne nt of t he ta blets s u bstit ute d wit h a c o m bi nati o n of t he 2 mai n fillers 
micr ocr ystalli ne cell ul ose ( A vicel ®  P H -1 0 2) a n d ma n nit ol ( Pearlit ol ®  2 0 0 S D). 
8. 3  
St u d y Dr u g A d mi nistr ati o n  
St u d y dr u g is t o be a d mi nistere d o nl y t o s u bjects w h o ha ve pr o vi d e d writte n i nf or me d c o ns e nt 
a n d ha ve met t he criteria o utli ne d i n S e cti o ns 7. 1  a n d 7. 2 . St u d y dr u g will be a d mi nistere d orall y 
o nce dail y  f or 1 2 wee ks. (T a bl e 3 ).  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 1  of 8 0  
 
T a ble 3 . St u d y Dr u g D osi n g 
St u d y Dr u g Gr o u p  
D ose  
Tre at me nt Re gi me n  
A Q X -1 1 2 5 2 0 0 m g  
2 A Q X -1 1 2 5 1 0 0 m g ta blets  
2 ta blets, o nce dail y  
Place b o  
2 place b o ta blets  
 
T he first d ose of st u d y dr u g will be a d mi nistere d i n t he cli nic at Baseli ne  (Visit  2), o nce all 
Baseli ne  pr oce d ures are c o m plete d a n d t he s u bject has bee n ra n d o mize d. N o i n vesti gati o nal or 
c o m mercial a ge nts or t hera pies ot her t ha n t h os e descri be d i n S e cti o n 8. 1 1  ma y b e a d mi nistere d 
wit h t he i nte nti o n t o treat t he s u bject’s c o n diti o n.  
S u bjects will be i nstr ucte d t o ta ke t he st u d y dr u g wit h a glass of water  ar o u n d t he sa me ti me of 
da y wit h f o o d, or eat a li g ht meal n o m ore t ha n 4 h o urs pri or t o c o ns u m pti o n, f or 1 2 wee ks. O n 
st u d y visit da ys, s u bjects will be i nstr ucte d n ot t o ta ke t he st u d y dr u g bef ore t he visit a n d t o eat a 
li g ht meal n o m ore t ha n 2 h o urs pri or t o t he sc he d ule d visit. T he st u d y dr u g will be ta k e n duri n g 
t he st u d y visit after all assess me nts ha ve bee n c o m plete d. If t he s u bject h as i na d verte ntl y ta ke n 
t he st u d y dr u g pri or t o atte n di n g t he cli nic, t he cli nic d ose s h o ul d n ot be gi v e n. 
If a d ose is misse d, s u bjects s h o ul d ta ke t he d ose as s o o n as t he y re me m ber o n t he sa me da y. 
H o we ver, if it is t he ne xt da y, t h e misse d d ose s h o ul d be s ki p pe d a n d ne xt d ose ta ke n as n or mal. 
O nl y 1 d ose of st u d y dr u g ( 2 ta bl ets) s h o ul d be ta ke n eac h da y a n d a d o u bl e d ose s h o ul d n ot be 
ta ke n. 
Re mai ni n g  u n use d st u d y dr u g will be c ollecte d at  Wee k 6 a n d at  t he e n d of t he 1 2-wee k 
treat me nt. S u bjects will be i nstr ucte d t o ret ur n all use d wallets (i ncl u di n g p artiall y us e d a n d 
t h ose wit h u n use d s pare d oses) f or r ec o n ciliati o n at eac h st u d y visit. 
8. 4  
R a n d o miz ati o n 
Ra n d o mizati o n will be c o n d ucte d at Baseli ne  (Visit  2), after verif yi n g t hat t he s u bject meet s all 
i ncl usi o n criteria a n d h as n o ne of t he e x cl usi o n criteria. A p pr o xi matel y 1 0 0 male s u bjects wit h 
dia g n ose d C P/ C P P S will be ra n d o mize d t o eit her A Q X- 1 1 2 5 ( 2 0 0 m g) or place b o i n a 1: 1 rati o.  
A ce ntral, p er m ute d bl oc k ra n d o mizati o n sc he me will be use d wit h a select e d bl oc ki n g fact or 
( bl oc k size) deter mi ne d b ase d o n t he pr o p os e d all ocati o n rati o a n d n u m ber of s u bjects. 
A n I nteracti ve We b Res p o nse S yste m (I W R S) will be use d f or t he ra n d o mi zati o n t o eit her A Q X-
1 1 2 5 ( 2 0 0 m g) or place b o a n d s u bse q ue nt wallet assi g n me nts. S t u d y staff will l o g i n t o t he 
I W R S usi n g a p pr o priate cre de ntials a n d i n p ut s u bject-s pecifi c i nf or mati o n (i.e. s u bject n u m ber 
a n d ot her basic i d e ntifiers). I n acc or da n ce wit h t h e ra n d o mizati o n sc he d ule, t he I W R S will 
assi g n t he ra n d o mizati o n n u m ber a n d t he u ni q ue wallet  n u m bers t o t he s u bject. Eac h s u bject 
m ust be gi ve n o nl y t he w allet s assi g ne d b y IW R S. T he st u d y staff will d oc u me nt t he wallet 
n u m bers i n t he Case R e p ort For m ( C R F) . S u bjects are t o be ra n d o mize d i n t he or der i n w hi c h 
t he y q u alif y fr o m t he scr ee ni n g p hase f or i ncl usi o n i n t he st u d y. 
 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 2  of 8 0  
 
8. 5  
St u d y Dr u g Bli n di n g  
Bli n di n g will be mai ntai ne d via pac k a gi n g ( S e cti o n 8. 6 ) a n d la b elli n g (S e cti o n 8. 7 ). La bels will 
c o ntai n fi x e d (e. g., pr ot o c ol n u m ber) a n d v aria ble i nf or mati o n ( e. g., wallet n u m ber) i n a ma n n er 
t hat pr otects t he bli n d.  
T he I n vesti gat ors, st u d y pers o n nel, s u bjects, me di cal m o nit or, a n d cli nical m o nit or will re mai n 
bli n de d t hr o u g h o ut t he st u d y, u nless safet y c o n cer ns necessitate u n bli n di n g. 
If a me dical e mer ge nc y o cc urs a n d a decisi o n re gar di n g t he s u bject’s cli nical treat me nt re q uires 
k n o wle d ge of t he tr eat me nt assi g n me nt, t he st u d y bli n d ma y be br o k e n f or t he s pecific s u bject. 
U nless t he me dical e m er ge n c y is dee me d t o b e life -t hreate ni n g, the me dical m o nit or m ust first be 
c o ns ulte d bef or e u n bli n di n g. T he I n vesti gat or w o ul d t he n utilize  t he I WR S  f or u n bli n di n g a n d 
t he u n bli n di n g pr oce d ure will be pr o vi de d i n t he I W R S Ma n ual. T he date, ti me, a n d reas o n f or 
u n bli n di n g m ust be d oc u me nte d i n t he s o urce d o c u me nts a n d o n t he a p plica ble electr o nic Case 
Re p ort F or m ( e C R F ). I n v esti gat ors s h o ul d n ote t hat t he occ urre nce of a S A E s h o ul d n ot 
r o uti nel y tri g ger i m me diate u n bli n di n g. If t he me dical m o nit or was n ot n otifie d pri or t o brea ki n g 
t he bli n d, t he I nv esti gat or  m ust n otif y t he me dical m o nit or of a n y a n d all bli n ds br o ke n wit hi n 2 4 
h o urs of eac h occ urre n ce. 
8. 6  
St u d y Dr u g P ac k a gi n g 
T he ta blets ar e pac k a ge d i n blister pac ks,  wit h 2 blister pac ks c o ntai ni n g a t otal of a 1 4- da y 
s u p pl y a n d 2 s pare d oses, asse m ble d i nt o a c hil d-resista nt car d b oar d wallet. Base d o n a d osi n g 
re gi me n of 2 ta blets a d a y, t he w allet desi g n will c o ntai n a t otal of 3 2 ta blets/ 1 6 d oses.  
 
Fi g ure 2 . T a blet p ac k a gi n g 
 
S ufficie nt q ua ntities of w allets will be dis pe nse d t o e na ble t he s u bject t o c o nti n ue t o ta ke t he 
me dicati o n u p t o t he ne xt st u d y visit. T he s pare d oses will all o w t he s u bjects t o re mai n o n 
treat me nt if t heir visit is a fe w d a ys p ost t he tar get visit date b ut wit hi n pre defi ne d acce pt a ble 
wi n d o ws. 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 3  of 8 0  
 
8. 7  
St u d y Dr u g L a belli n g  
T he wallet will be la belle d wit h a si n gle pa n el la bel, wit h tra nslati o ns pr o vi de d f or official 
la n g u a ges of t he c o u ntries/cli nical sites partici pati n g i n t he st u d y. B ot h p ac ka gi n g a n d la belli n g 
will be c o n d ucte d as p er re g ulat or y g ui de li nes. 
La b els will c o ntai n fi x e d (e . g., pr ot oc ol n u m ber) a n d varia ble i nf or m ati o n (e. g., wallet n u m ber) 
i n a ma n ner t hat pr ot ects t he bli n d.  
8. 8  
St u d y Dr u g St or a ge 
St u d y dr u g s h o ul d be st ore d at r o o m te m perat ure ( 1 5 t o 2 5° C/ 5 9 t o 7 7° F wit h e x c ursi o ns u p t o 
3 0° C/ 8 6° F per mitte d). I nstr ucti o ns f or ha n dli n g t e m perat ure e x c ursi o ns are detaile d i n t he St u d y 
Ma n ual.  R o o m te m perat ure rea di n gs at site are t o be rec or de d wit h a n y d e viati o ns o utsi de of t he 
per mitte d ra n ge d re p ort e d. St u d y dr u g s h o ul d be st ore d i n a sec ur e, l oc k e d facilit y accessi ble 
o nl y t o a ut h orize d st u d y pers o n nel u ntil dis pe nse d t o t he st u d y s u bject. I nstr ucti o ns f or or d eri n g 
dr u g will be s pecifie d i n t he St u d y Ma n ual a n d will be distri b ute d t o t he st u d y ce nters b y a 
ce ntralize d distri b uti o n ser vice.  
8. 9  
St u d y Dr u g H a n dli n g a n d Acc o u nt a bilit y  
Rec or ds s hall be mai ntai ne d of t he deli ver y of st u d y dr u g(s) t o t he st u d y ce nter(s), t he i n ve nt or y 
at t he st u d y ce nter(s), t he use b y eac h s u bj ect a n d t he ret ur n of u n use d st u d y dr u g t o t he 
distri b uti o n ce nters ( per t he St u d y Ma n u al ). 
T hese rec or ds s hall i ncl u de dates, q ua ntities, batc h n u m bers, e x pir y dates a n d t he u ni q ue wallet  
n u m bers assi g n e d t o t he st u d y me dicati o n a n d t o t he st u d y s u bjects. 
T he I n vesti gat or s hall be res p o nsi ble f or e ns uri n g a de q uate d o c u me ntati o n of st u d y dr u g 
recei v e d, dis pe nse d, a n d ret ur ne d.  
8. 1 0  
Tre at me nt a n d Elect r o nic Di ar y C o m pli a nce  
T reat me nt c o m plia nce will be assesse d t hr o u g h ta blet c o u nts. T he s u bject will be i nstr ucte d t o 
bri n g all dis pe nse d wallets bac k  t o t he cli nic at eac h visit (e ve n if t he w allet is e m pt y). T he 
n u m ber of use d a n d re mai ni n g ta blets will be rec or de d o n t he eC R F.  
S u bject c o m plia nce wit h t he e Diar y will be m o nit ore d b y trai ne d st u d y site pers o n nel at eac h 
st u d y visit. 
8. 1 1  
C o nc o mit a nt Me dic ati o ns  
8. 1 1. 1  
Per mitte d Me dic ati o ns  
T he use of sta ble c o nc o mita nt t hera p y is all o we d t hr o u g h o ut t he st u d y, e x ce pt f or t h ose 
me dicati o ns pr o hi bite d i n S e cti o n 8. 1 1. 2 . All c o n c o mita nt me dicati o n s m ust be rec or d e d i n t he 
a p pr o priate s ecti o ns of t h e e C R F  or t he e Diar y as a p pr o priate , a n d u p date d if a n y c ha n ges occ ur. 
C o nc o mita nt me dicati o ns s h o ul d i ncl u de all me dicati o ns ta ke n wit hi n 3 0 da ys pri or t o Scree ni n g 
Visit 1 a n d t hr o u g h o ut t h e st u d y.  
T he f oll o wi n g m e dicati o ns are per mitte d f or use d uri n g t he st u d y: 
•  S h ort-acti n g o pi oi d or o pi oi d- c o ntai ni n g a n al gesics  (e. g., aceta mi n o p he n + c o dei ne) f or 
treat me nt of pai n, i ncl u di n g C P/ C P P S s y m pt o m flares b ut treat me nt per pr ot oc ol is o nl y 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 4  of 8 0  
 
per mitte d f or f e wer t h a n 5 da ys p er w ee k or n o m ore t ha n 1 0 d oses p er m o nt h 
•  N o n - o pi oi d-c o ntai ni n g a nal gesics (e . g., acet a mi n o p he n) 
•  N o n -ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds) o nl y if o n a sta bl e d ose (i.e. sta ble 
patter n  a n d fre q ue n c y of use) f or ≥3 0 d a ys pri or t o Scree ni n g Visit  1 
•  M e dicati o ns f or treati n g disease s ot her t ha n C P/ C P P S are per mitte d, pr o vi de d t he y are 
n ot i ncl u de d i n t he list of pr o hi bite d me dicati o ns liste d i n S e cti o n 8. 1 1. 2 . 
•  Me dicati o ns f or treati n g C P/ C P P S are per mitte d, pr o vi de d t he y are n ot i ncl u de d i n t he list 
of pr o hi bite d me dicati o ns liste d i n S e cti o n 8. 1 1. 2 , a n d t he s u bject has b ee n o n a sta ble 
d ose f or ≥3 0 da ys pri or t o Scree ni n g Visit 1 a n d pla ns t o  c o nti n ue c urre nt patter n of 
usa ge f or t he d urati o n of t he st u d y. 
8. 1 1. 2  
Pr o hi bite d Me dic ati o ns 
T he f ol l o wi n g m e dicati o ns are pr o hi bite d f or use d uri n g t he st u d y: 
•  A n y l o n g -acti n g o pi oi ds 
•  Oral ster oi d t her a p y, i m m u n os u p pressa nts/i m m u n o m o d ulat ors (i ncl u di n g dail y 
p h os p h o diesterase t y pe 4 i n hi bit ors)  
If a s u bject re q uires s h ort-acti n g o pi oi d a nal gesics f or ≥5  da ys per wee k o n > 1 occ urre n ce d uri n g 
t he st u d y or > 1 0 ti mes per m o nt h o n > 1 occ urre nce d uri n g t h e st u d y, or re q uire a pr o hi bite d 
me dicati o n t o treat a n A E, t he s u bject ma y re m ai n i n t he st u d y . T he use of t he pr o hi bite d 
me dicati o n s h o ul d be ca pt ure d o n t he e C R F.  
9  
S T U D Y A S S E S S M E N T S  
Refer t o T a bl e 1  f or sc he d uli n g of st u d y assess me nts.  
9. 1  
Eli gi bilit y  O nl y Assess me nts  
9. 1. 1  
De m o gr a p hics, B aseli ne C h ar acteristics , Me dic al/ S ur gic al Hist ory  
De m o gra p hic i nf or mati o n, i ncl u di n g a ge, birt h ye ar, se x, race a n d et h nicit y. 
Baseli ne c har acteristics c o nsist of a c o m plete me dical hist or y a n d detaile d disease hist or y. 
Me dical hist or y i n cl u des pri or a n d o n g oi n g me dical dia g n os es a n d c o n diti o ns, s ur gical 
pr oce d ur es, a n d me dicati o ns ta ke n wit hi n t he pre vi o us 3 0 da ys. Bac k gr o u n d i nc i de nce of 
catar acts i n s u bjects n ote d pri or t o d osi n g s h o ul d be rec or de d as me dical hist or y. 
T his i nf or mati o n will be c ollecte d at scree ni n g ( Visit 1).  
9. 1. 2  
Uri n ary, Psyc h os oci al, Or g a n S pecific, I nfecti o n, Ne ur ol o gic/ Syste mic, Te n der ness 
of S kelet al M uscles Di a g n osis 
T he  Uri nar y, Ps yc h os o ci al, Or ga n S pecific, I nfecti o n, Ne ur ol o gic/ S yste mic, Te n der n ess of 
S keletal M uscles  (U P OI N T ) s yst e m is desi g n e d t o classif y patie nts wit h a n esta blis he d dia g n osis 
of C P/ C P P S i nt o a cli nicall y r ele va nt p he n ot y p e t hat ca n rati o nall y g ui de t hera p y. Usi n g t he 
we bsite  htt p:// w w w. u p oi nt m d.c o m  ( S h os kes, et al., 2 0 1 3), s u bjects will be classifie d  i nt o t he 6 
d o mai ns of t he U P OI N T s yste m ( Uri nar y, Ps yc h os ocial, Or ga n S pecific, I nfecti o n, 
Ne ur ol o g ic/ S yste mic, T e n der ness of S kelet al M uscles). T he classificati o n will be d o ne at 
scree ni n g ( Visit 1) o nl y. 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 5  of 8 0  
 
9. 1. 3  
P ai n C at astr o p hizi n g Sc ale 
T his 1 3- state me nt P C S is ca pt ure d o nl y at s cree ni n g (Visit  1), (A p p e n di x 1. P ai n 
C at a str o p hi zi n g S c al e) a n d atte m pts t o elicit t he s u bject’s t y p es of t h o u g hts a n d feeli n g w h e n i n 
pai n. Catastr o p hizi n g is defi ne d as a n e x a g gerat e d ne gati ve me ntal set br o u g ht t o bear d uri n g 
act ual or a ntici p ate d pai nf ul e x perie nce ( S ulli v a n et al., 2 0 0 1 ). A s u bject is e x cl u de d fr o m t he 
st u d y if t he t otal sc or e fr o m t hese q uesti o ns is ≥3 0 (S ulli v a n et al ., 1 99 5) . 
9. 1. 4  
P atie nt He alt h Q uesti o n n aire  9-Q uesti o n  
T he P H Q - 9 is a 9-ite m p atie nt self-r e p orti n g t o ol use d t o assist st u d y pers o n nel i n i de ntif yi n g 
m o o d c ha n ges b y scree ni n g f or s y m pt o ms of d e pressi o n ( Kr o e n k e et al., 2 0 0 1 , A p pe n di x 2. 
Patie nt Healt h Q uesti o n naire 9 -It e ms). Q uesti o n 9 scree ns f or t he prese n ce of s uici dal i deati o n.  
A s u bject wit h a t otal sc ore ≥1 0 fr o m t hese q u esti o ns at Scree ni n g ( Visit 1) or Bas eli ne ( Visit 2), 
or if i n t he o pi ni o n of t he I n v esti gat or, fi n di n gs o n t he Bas eli ne ( Visit 2) P H Q -9 i n dicate n e wl y 
i de ntifie d or p o orl y ma na ge d m e ntal healt h c o n cer ns w hic h w o ul d p ut t he s u bject at ris k or 
c o m pr o mise t heir a bilit y t o partici pate i n t he st u d y a n d c o m pl y wit h st u d y re q uire me nts, t he 
s u bject will  be e x cl u de d fr o m t he st u d y. 
S u bjects wit h a n o verall sc ore o n t he s elf -re p orte d P H Q- 9 ≥1 0 or a sc ore o n Q uesti o n 9, relate d 
t o t h o u g hts of wa nti n g t o h urt o neself, of ≥1 ha v e a hi g h er li keli h o o d of t he prese nce of a m o o d 
dis or der.  A n y s u bject wit h a sc ore a b o ve t hese t hres h ol ds will be see n b y a me m ber of t he 
cli nical st u d y staff pri or t o lea vi n g t h at st u d y visit.  St u d y st aff will f urt her cli nicall y ass ess 
w het her t he s u bject is e x perie nci n g de pressi ve s y m pt o ms, s uici dal t h o u g hts or be ha vi ors, a n d 
w het her t hes e s y m pt o ms, if prese nt, are c h a n ge d fr o m baseli ne.  If t he fi n di n gs re pres e nt a 
c ha n ge, t his c ha n ge i n s y m pt o ms/ m o o d, n ot t he P H Q- 9 sc ore,  will be rec or de d as a n A E, a n d t he 
s u bject will be cli nicall y ma na ge d b y t he I n v esti gat or.  T his pr oce d ure all o ws f or s u bjects t o be 
i de ntifie d a n d ma na ge d i n a cli nical setti n g a n d t h e data t o be ca pt ure d i n t he cli nical st u d y 
data base  as A Es.  
T his will be perf or me d at Visits 1, 2, 3, 4, E T (if nee de d), a n d at t he Off- Treat me nt Safet y 
F oll o w- u p Visit.  
9. 1. 5  
Uri ne: B acteri al C ult ure & S e nsitivity, Le u k ocyte Ester ase Test 
A uri ne bact erial c ult ur e will be o btai ne d at scree ni n g (Visit  1) o nl y. A s u bj ect will be e x cl u de d 
fr o m t he st u d y if t h e s u bject has s y m pt o ms c o nsiste nt wit h a uri nar y tract i nfecti o n a n d a p ositi ve 
uri ne bacterial c ult ure, d efi ne d as ≥1 0 5 c ol o n y f or mi n g u nits ( C F U) p er m L or ≥1 0 4 Gra m 
ne gati ve r o d C F U  per m L . A s u bject ca n rescree n u p t o 1 ti me o nce t he i nfecti o n clears.  A 
le u k oc yt e esterase test will be c o n d ucte d b y t he sit e at scree ni n g (Visit  1) o nl y.  
9. 2  
Effic ac y Assess me nts  
9. 2. 1  
1 1- p oi nt N u m er ic al R ati n g Sc ale 
T his scale will be use d t o deter mi ne t he pri mar y a n d sec o n dar y N R S pai n e n d p oi nts ( A p pe n di x 
3. 1 1- p oi nt N u merical Rati n g Scale ). T he s u bject will be as ke d t o rate b ot h t heir a vera ge a n d 
ma xi m u m  ( w orst) pel vic pai n i nte nsit y f or t he d a y o n a dail y b asis usi n g t h e e Diar y . S u bjects 
will als o be as ke d t o rate b ot h t heir a vera ge a n d m a xi m u m ( w orst) pel vic pai n i nte nsit y usi n g t h e 
pa per versi o n d uri n g t he i n- cli nic visits ( Visits 1, 2, 3, 4, E T (if nee d e d), a n d at t he Off-

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 6  of 8 0  
 
Treat me nt Saf et y F oll o w -u p Visit) . S u bjects will be as ke d t o rate t heir pel vic pai n o n a scal e of 
0- 1 0, b y i n dicati n g t he n u m ber t hat best descri bes t he pai n i nte nsit y. 
9. 2. 2  
N ati o n al I nstit utes of He alt h, C hr o nic Pr ost atitis Sy m pt o m I n de x   
T he  NI H - C P SI is a c o m m o nl y use d 1 3-ite m q uesti o n naire f or t he assess me nt of s y m pt o m 
se verit y i n me n wit h C P/ C P P S. F or eac h ite m, sc ore ra n ges are 0– 1 ( 6 ite ms), 0 – 3 ( 2 ite ms), 0 – 5 
( 3 ite ms), 0– 6 ( 1 ite m), a n d 0 – 1 0 ( 1 ite m) ( Lit wi n et al ., 1 9 9 9, A p p e n di x 4. N ati o n al I nstit ut es 
of H e alt h  C hr o ni c Pr ost atitis S y m pt o m I n d e x ). T his will be perf or me d at Visits 1, 2, 3, 4, E T 
(if nee d e d), a n d at t he Off-Treat me nt Safet y F oll o w -u p Visit.  
9. 2. 3  
I nter n ati o n al I n de x of Erectile F u ncti o n Q uesti o n n aire  
T he 1 5- q uesti o n II E F Q u esti o n naire is a vali date d, m ulti - di me nsi o nal, self-a d mi nistere d 
i n vesti gati o n t hat has bee n f o u n d usef ul i n t he cli nical assess me nt of erectile d ysf u ncti o n a n d 
treat me nt o utc o mes i n cli nical trials (R ose n  et al., 1 9 9 7). A sc ore of 0- 5 is a war de d t o eac h of t he 
1 5 q uesti o ns t hat e x a mi ne t he 5 mai n di me nsi o ns of male se x ual f u ncti o n: erectile f u ncti o n, 
or gas mic f u ncti o n, se x ual desire, i nterc o urse satisfacti on a n d o verall satisfacti o n  (A p p e n di x 5. 
I nt er n ati o n al I n d e x of Er e ctil e F u n cti o n Q u esti o n n air e). T he e ntire q uesti o n naire will be 
a d mi nistere d t o t he s u bject, h o we ver, o nl y t he first 5 q uesti o ns ass ociate d wit h t he Erectile 
F u ncti o n d o mai n will be use d f or t he efficac y ass ess me nts.  
T his i nf or mati o n will be c ollecte d at Visits 2, 3, 4, E T (if nee d e d), a n d at t he Off- Treat me nt 
Safet y F oll o w -u p Visit.  
9. 2. 4  
Gl o b al Res p o nse Assess m e nt  
Assess me nt of t he s u bject’s gl o bal s y m pt o ms, c o m pare d wit h Baseli ne  s y m pt o ms, will be 
perf or me d b y t h e s u bject  usi n g a 7-ite m scale (A p pe n di x 6. Gl o bal Res p o nse Assess me nt ). T his 
i nf or mati o n will be c ollecte d at Visits 3, 4, E T (if nee de d), a n d at t he Off-Treat me nt Safet y 
F oll o w- u p Visit.  
9. 2. 5  
P atie nt’s Gl o b al I m pressi o n of C h a n ge Sc ale 
Assess me nt of t he s u bject’s o verall stat us si nce Baseli ne, will be  perf or me d b y t he s u bject usi n g 
a 7- ite m scale (A p pe n di x 7. Patie nt’s Gl o bal I m pressi o n of C ha n ge Scale ). T his i nf or mati o n will 
be c ollecte d at Visits 3, 4, E T (if nee d e d) , a n d at t he Off-Treat me nt Safet y F oll o w - u p Visit. 
9. 2. 6  
P atie nt’s Gl o b al I m pressi o n of Severity Sc ale  
Assess me nt of t he s u bject’s c urre nt s y m pt o ms will be perf or m e d b y t he s u bject usi n g a 5- ite m 
scale (A p p e n di x 8. Patie nt’s Gl o bal I m pressi o n of Se verit y Scale ). T his i nf or mati o n will be 
c ollecte d at Visits 2, 3, 4, E T (if nee d e d), a n d at t he Off- Treat me nt Safet y F oll o w -u p Visit.  
9. 2. 7  
T we nty -f our H o ur V oi di n g Fre q ue ncy 
V oi di n g fr e q ue n c y will be meas ur e d o ver a 2 4- h o ur peri o d, wit hi n a 3- da y ( 7 2 h o urs) wi n d o w 
bef ore s c he d ule d v isits ( Visit 2, 3, 4, E T (if nee de d), a n d at t he Off-Treat m e nt Safet y F oll o w - u p 
Visit.   

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 7  of 8 0  
 
9. 3  
S af et y Assess me nts  
9. 3. 1  
P hysic al E x a mi n ati o n, Vit al Si g ns  
A c o m plete ge n eral p h ysical e x a mi nati o n  cate g ori ze d b y b o d y s yste m (e. g ., hea d, e yes, ears, 
n ose t hr oat; nec k ; c h est; l u n gs; bac k ; a b d o me n; di gital rectal e x a m [at Scree ni n g Visit 1 o nl y]; 
e xtre mities ; a n d ne ur ol o gical), a n d vital si g ns, will be assesse d a n d rec or de d at Visits 1, 2, 4, E T 
(if nee d e d), a n d at t he Off-Treat me nt Safet y F oll o w -u p Visit.  Vital si g ns will als o be ta ke n at 
Visit 3.  Wei g ht will be d o ne at Visits 1, 4, E T (if nee de d), a n d at t he Off- Treat me nt Safet y 
F oll o w- u p Visit. Hei g ht will be meas ure d at Visit 1. Seate d bl o o d press ure ( B P ) ( m m H g), h eart 
rate (H R ) ( beats p er mi n ute) a n d te m perat ure ( de grees Celsi us) will be meas ure d after t he s u bject 
has bee n sitti n g f or at least 5 mi n utes.  
9. 3. 2  
O p ht h al mic Assess m e nts  
O p ht hal mic assess me nts will be perf or me d d uri n g t he st u d y. Scree ni n g o p ht hal mic assess me nts 
ca n be p erf or m e d a n y ti me wit hi n t he scree ni n g wi n d o w ( Visit 1a).  P ost- Baseli ne o p ht h al mic 
assess me nts  ( Visit 4, E T [if nee de d], Off-Treat me nt Safet y F oll o w - u p Visit, a n d O p ht hal mic 
F oll o w- u p Visit) s h o ul d occ ur wit hi n t he s pecifie d Visit wi n d o ws. 
T he assess me nts will i ncl u de t he f oll o wi n g: 
•  B C V A  usi n g t he L o g M A R  c hart (i.e., after ma nifest refracti o n) 
•  I O P, pr ef era bl y meas ure d b y  G ol d ma n n t o n o metr y, bef ore a n d aft er dilati o n wit h 
m y driatic a ge nt  
•  C or neal stai ni n g 
•  S lit la m p e x a mi nati o n  
•  Le ntic ul ar o pacificati o n usi n g L O C S III   
Bac k gr o u n d i nci de n ce of catar acts i n s u bjects n ote d pri or t o d osi n g s h o ul d be rec or de d as 
me dical hist or y.  A n y cli nicall y si g nifica nt oc ular fi n d i n gs m ust be re p ort e d as A Es . Refer t o 
S e cti o n 9. 3. 5. 5  f or s pecific details c o ncer ni n g oc ular A Es a n d d efi niti o n of oc ular S A Es. 
9. 3. 3  
1 2-le a d S u pi ne Electr oc ar di o gr a m 
S u bjects will be resti n g s u pi ne f or at least 5 mi n utes bef ore t he electr ocar di o gra m (E C G ) 
rec or di n g. T h e I n vesti gat or will deter mi ne if a n y a b n or mal E C G res ults  are cli nicall y si g nifica nt 
a n d if s o, rec or d t hese o n t he a p pr o priat e s o urce d oc u me nt a n d o n t he A E C R F pa ge. T his 
assess me nt will be perf or me d at Visits 1, 4, E T (if nee de d), a n d at t he Off-Treat me nt Safet y 
F oll o w- u p Visit.  
9. 3. 4  
Cli nic al C he mistry & He m at ol o gy, Uri n alysis  
Bl o o d sa m ples will be c ollecte d f or cli nical la b orat or y tests a n d pr ocess e d b y a ce ntral 
la b orat or y. S u bjects d o n ot nee d t o be fasti n g f or t he bl o o d dra w. T his ass es s me nt will be 
perf or me d at Visits 1, 2, 4, E T (if nee d e d), a n d at t he Off- Treat me nt Safet y F oll o w - u p Visit. T he 
f oll o wi n g la b or at or y tests will be assesse d  (T a bl e 4 ): 
 
 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 8  of 8 0  
 
T a ble 4 . Cli nic al  L a b or at or y Tests  
Ser u m C he mistr y  
He m at ol o g y  
Uri n al ysis  
 
Urea  
 
Gl uc ose  
 
As partate a mi n otra nsferase ( A S T)  
 
Ala ni ne a mi n otra nsferase ( A L T)  
 
Al kali ne p h os p hatase ( A P)  
 
Lactate de h y dr o ge nase ( L D H)  
 
S o di u m  
 
P h os p hate  
 
P otassi u m  
 
C hl ori de  
 
Creati ne p h os p h o ki nase ( C P K)  
 
Gl o b uli n  
 
C h olester ol  
 
Creati ne  
 
Ser u m calci u m  
 
T otal bilir u bi n  
 
Tri gl yceri de  
 
Ga m ma gl uta m yl tra ns pe pti dase 
( G G T) 
 
Uric aci d  
 
He mat ocrit  
 
He m o gl o bi n  
 
Re d Bl o o d Cell C o u nt  
 
W hite Bl o o d Cell C o u nt 
wit h Differe ntial  
 
Platelet C o u nt  
 
Mea n c or p usc ular v ol u me  
 
Mea n c or p usc ular 
he m o gl o bi n  
 
Mea n c or p usc ular 
he m o gl o bi n c o nce ntrati o n  
 p H  
 Pr otei n  
 Gl uc ose  
 Ket o nes  
 Bilir u bi n  
 S pecific Gra vit y  
 Bl o o d  
 Nitrites  
 Ur o bili n o ge n  
 B acterial c ult ure & 
se nsiti vit y, le u k oc yte 
esterase test  (Scree ni n g 
Vi sit o nl y) 
 
T he ce ntr al la b orat or y will pr o vi de a la b orat or y m a n ual a n d a p pr o priate s u p plies (c o ntai ners a n d 
la bels). La b or at or y val ues t hat are o ut of ra n ge will be i de ntifie d a n d ma y b e re peate d at t he 
I n v esti gat or’s discr eti o n. T he I n vesti gat or will det er mi ne if a n y o ut -of -ra n ge la b orat or y v al ues 
are cli nicall y si g nifica nt a n d if s o, rec or d t hese o n t he a p pr o priat e s o urce d oc u me nt a n d o n t he 
A E C R F pa ge. All cli nicall y si g nifica nt o ut -of -ra n ge l a b orat or y v al ues will be f oll o we d u ntil 
t he y r et ur n t o n or mal, or bec o me me dicall y sta bl e.  
9. 3. 5  
A dverse Eve nt Defi niti o ns/ Re p orti n g Re q uire m e nts  
A n A E (als o k n o w n as a n “a d vers e e x perie nce”) is defi ne d as a n y u nt o war d me dical occ urre n ce 
i n a patie nt  or cli nical i n vesti gati o n s u bject a d mi nistere d  a p har mace utical  pr o d uct a n d w hic h  
d oes n ot necess aril y h a ve t o ha ve a ca usal relati o ns hi p wit h t his treat me nt  (I C H E 2 A Cli nical 
Safet y Data M a na ge m e nt: Defi niti o ns a n d Sta n dar ds f or E x pe dite d Re p orti n g ).  
A n A E ca n t h eref ore b e a n y u nf a v ora bl e a n d u ni nt e n de d si g n (i ncl u di n g a n a b n or mal la b orat or y 
fi n di n g), s y m pt o m, or dis ease te m p or all y ass ociate d wit h t he use of t he dr u g, wit h o ut a n y 
j u d g me nt a b o ut ca usalit y.  
All cli nical A Es  n ote d d uri n g t he st u d y will be re p orte d o n t he a p pr o priate A E pa ge of t h e eC R F.  
A E s t hat are s eri o us, u ne x pecte d, a n d at least p ossi bl y relat e d t o st u d y p artici pati o n will be 
re p orte d t o t he I nstit uti o nal Re vie w B o ar d (I R B) or I E C a n d t o t he U nite d States ( U S ) F o o d a n d 
Dr u g A d mi nistrati o n ( F D A ) or Healt h Ca na da wit hi n t he ti meli nes des cri be d bel o w. All ot her 
A Es, s uc h as t h ose t hat are e x pecte d, or n ot relate d t o t he st u d y partici p ati o n, are t o be re p orte d 
a n n uall y t o t he i nstit uti o n’s I R B/I E C at t he ti me of t he a n n ual C o nti n ui n g Re vie w a n d t o F D A as 
part of re g ul ar dat a s u b missi o n at t he ti me of a n n ual I n v esti gati o nal Ne w Dr u g (I N D) re p ort.  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 3 9  of 8 0  
 
9. 3. 5. 1  
E x pecte d E ve nts  
E x pecte d e ve nts ar e t h ose t hat ha ve b ee n pre vi o usl y i de ntifie d as res ulti n g fr o m a d mi nistrati o n 
of t he st u d y dr u g. A n A E  is c o nsi dere d u ne x pecte d, f or e x pe dite d re p orti n g p ur p oses o nl y, w he n 
eit her t he t y pe of e ve nt or t he se verit y of t h e e ve nt is n ot liste d i n t he c urre nt I B. 
9. 3. 5. 2  
S us pecte d A d verse Re a cti o n  
A s us pecte d a d v erse reacti o n is a s u bset of all A Es f or w hic h t here is a reas o na ble p ossi bilit y 
(i.e. e vi de nce t o s u g gest a ca usal relati o ns hi p bet wee n t he dr u g a n d t he A E) t hat t he dr u g ca use d 
t he e ve nt. S us pecte d a d v erse r eacti o n i m plies a lesser de gree of cert ai nt y a b o ut ca usalit y t ha n 
a d verse reacti o n.   
9. 3. 5. 3  
A d verse R e acti o n  
A n a d vers e reacti o n is a s u bset of all s us pecte d a d verse reacti o ns, a n d is defi ne d as a n y A E 
ca use d b y a dr u g.   
9. 3. 5. 4  
Seri o us A d verse E ve nt Defi niti o ns / Re p orti n g Re q uire me nts  
9. 3. 5. 4. 1  Seri o us A dverse Eve nt or Seri o us S us pecte d A dverse Re acti o n  
A n A E or s us pect e d a d verse reacti o n is c o nsi dere d seri o us if, i n t he vie w of eit her t he 
I nvesti g at or or S p o ns or, it res ults i n a n y of t he f oll o wi n g o utc o mes:  
De at h : 
T his i ncl u des a n y d eat h t hat occ urs w hile t h e s u bject  is o n st u d y a n d/ or wit hi n 2 8 da ys after t he 
last d ose of st u dy dr u g.  A n a ut o ps y will be re q ueste d, a n d if perf or me d, res ults will be s u b mitte d 
t o t he S p o ns or.  
A life -t hre ate ni n g A E : 
A n A E or s us pect e d a d verse reacti o n is c o nsi dere d life-t hreat e ni n g if, i n t he vie w of eit her t he 
I nvesti g at or or S p o ns or, its occ urre n ce places t he s u bject at i m me diate ris k of deat h.  It d oes n ot 
i ncl u de a reacti o n t hat ha d it occ urre d i n a m ore se vere f or m, mi g ht ha v e ca use d deat h. 
I n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n: 
I n t he a bse n ce of a n A E, h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n s h o ul d n ot be re p orte d 
as a n S A E i n t he f oll o wi n g sit uati o ns: 
•  H os pitalizati o n or pr ol o n gati o n of h os pitalizati o n is nee de d f or a pr o ce d ure re q uire d b y 
t he pr ot oc ol 
•  H os pitalizati o n or pr ol o n gati o n of h os pitalizati o n is part of r o uti ne pr oce d ure f oll o we d b y 
st u d y ce nt er  
•  H os pitalizati o n f or s u r ve y visits or a n n ual p h ysicals 
•  F or a h os pitalizati o n pla n ne d (a n d d oc u m e nte d) b ef ore t he start of t he st u d y f or a pre-
e xisti n g c on diti o n w hic h has n ot w orse ne d 
 
A persis te nt or si g nific a nt i nc a p acity or s u bst a nti al disr u pti o n of t he a bility to c o n d uct n or m al 
life f u ncti o ns 
A c o n ge nit al a n o m aly/ birt h defect 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 0  of 8 0  
 
A n i m p ort a nt m e dic al eve nt:  
I m p ort a nt me dical e v e nts t hat ma y n ot res ult i n deat h, be life-t hreate ni n g, or re q uire 
h os pitalizati o n ma y be c o nsi dere d seri o us w h e n, base d u p o n a p pr o priate me dical j u d g m e nt, t he y 
ma y je o p ar dize t he s u bject a n d ma y re q uire me dical or s ur gical i nter v e nti o n t o pre ve nt o ne of t h e 
o utc o mes liste d i n t his defi niti o n.  E x a m ples i ncl u de aller gic br o n c h os pas m re q uiri n g i nte nsi ve 
treat me nt i n a n e mer ge nc y r o o m or at h o me, bl o o d d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n 
i n patie nt h os pitalizati o n, or t he de vel o p me nt of dr u g de p e n de n c y or dr u g a b use.  
T he S p o ns or s h o ul d be n otifie d wit hi n 2 4 h o urs of t he I n v esti gat or bec o mi n g a ware of a S A E 
a n d t he e ve nt d o c u me nte d o n t he e C R F. 
9. 3. 5. 4. 2  Seri o us U ne x pecte d a n d S us pecte d A dverse Re acti o n  
A n u ne x pecte d A E ( or S U S A R ) is a n y A E or s us pecte d a d v erse reacti o n t hat is n ot liste d i n t he 
I B or is n ot liste d at t he s peci ficit y or se v erit y t hat has bee n o bser ve d, or, if a n I B is n ot 
re q uire d/a v aila ble, is n ot c o nsiste nt wit h t he ris k i nf or mati o n descri b e d i n t he ge neral 
i n vesti gati o nal pla n. T his als o refers t o A Es or s us pecte d a d v erse reacti o ns me nti o ne d i n t he I B 
as occ urri n g wit h a class of dr u gs or as a ntici pate d fr o m t he p har mac ol o gical pr o perties of t h e 
dr u g, b ut are n ot s pecificall y me nti o ne d as occ urri n g wit h t he st u d y dr u g. A S U S A R  re q uires 
ma n dat or y e x pe dite d re p orti n g t o t he a p plica ble re g ul at or y a ut h orit y(ies) ( refer t o S e cti o n 
9. 3. 5. 8 ). T he S p o ns or will f or war d t he f or mal n otificati o n descri bi n g t he S U S A R t o 
I n v esti gat ors. Eac h I n vesti gat or m ust t he n n otif y his/ her I R B /I E C of t he S U S A R, i n acc or da n ce 
wit h t he I R B /I E C’s p olic y. 
9. 3. 5. 5  
O p ht h al mic E ve nt Re p orti n g  
A ll cli nicall y si g nifica nt oc ular fi n di n gs m ust be re p orte d as A Es.  
Oc ul ar Tre at m e nt E m er ge nt A dverse Eve nts of S peci al I nterest  
T he f oll o wi n g Oc ular A Es will be treate d as treat me nt e mer ge nt A Es  of s pecial i nterest  
(T E A E SIs ) 
•  A Class II or Class III gr a di n g s hift i n L O C S III as defi ne d i n t he O p ht hal m ol o g y Ma n ual 
c o m pare d t o Baseli ne   
•  A re d ucti o n of 2 li nes or m ore o n t he L o g M A R c h art i n B C V A c o m pare d t o Baseli ne 
•  Oc ular A Es wit h o ut clear eti ol o g y 
•  Oc ular A Es c o nsi der e d p ossi bl y or pr o ba bl y relate d t o st u d y dr u g 
Oc ular A Es wit h  clear eti ol o g y will be re vi e we d o n a case b y cas e basis t o deter mi ne if t he y 
s h o ul d be treate d as T E A E SIs. 
A dj u dic ati o n  
Oc ular T E A E SIs  will be assesse d b y a n i n de p e n de nt, bli n de d a dj u dicat or.  
Re p o rti n g of T E A E SI   
T E A E SIs will be  c o m m u nicate d t o t he Dr u g Safet y Ma n a ger t o e x pe dite S p o ns or re vie w of 
e ve nts. I n vesti gat ors m ust desi g nate w het her t he e ve nt is a n A E or w h et her it meets t he criteria 
of a n S A E (S e cti o n 9. 3. 5. 4. 1 ). 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 1  of 8 0  
 
9. 3. 5. 6  
Rec or di n g A d verse E ve nts  
F or t he p ur p os es of t his st u d y, a n y d etri me ntal c ha n ge i n t he s u bject's c o n diti o n, fr o m si g ni n g of 
i nf or me d c o nse nt u p t o c o m pleti o n of t he treat me nt peri o d s h o ul d be c o nsi dere d a n A E (i.e. f or 
u p t o 2 8 da ys after last d ose of i n vesti gati o nal pr o d uct has bee n ta k e n). 
A Es s h o ul d be ca pt ur e d w here v er p ossi ble as a dia g n osis a n d it is t he I n v esti gat or’s 
res p o nsi bilit y t o e ns ure t his is d o ne. If a precise dia g n osis ca n n ot be ma de, a s y n dr o me ca n be 
rec or d e d. Rar el y s h o ul d it be necess ar y t o rec or d o ne or m ore i n di vi d ual s y m pt o ms. 
All o n g oi n g n o n- oc ular A Es s h o ul d be f oll o we d u p u ntil t he Off -Treat me nt Safet y F oll o w - u p 
Visit ( f or 2 8 da ys aft er t h e last a d mi nistrati o n of st u d y dr u g), wit h t he e x ce pti o n of a n y o n g oi n g 
st u d y dr u g-relate d A Es, w hic h s h o ul d be f oll o we d u ntil res ol uti o n, u nless i n t he I n v esti gat or 's 
o pi ni o n t he A E is u nli kel y t o res ol v e d ue t o t he s u bject's u n d erl yi n g disease. O n g oi n g oc ul ar 
A Es will be q uerie d a t t h e F oll o w-u p call 3  m o nt hs p ost last d ose a n d at t he O p ht hal mic Safet y 
F oll o w- u p Visit 6  m o nt hs p ost last d ose. 
O c ular A Es  m ust be f oll o we d u ntil t he 6- m o nt h O p ht hal mic Safet y F oll o w- u p Visit.   
A n y n e w S A Es occ urri n g u p t o 2 8 da ys  after t he l ast a d mi nis trati o n of st u d y dr u g s h o ul d be 
re p orte d t o t he dr u g s afet y ma n a ger.   
At a n y ti me after t h e Off -Treat me nt Safet y F oll o w - u p Visit, if a n I n vesti gat or lear ns of a n S A E 
t hat ca n be r eas o n a bl y rel ate d t o st u d y dr u g, h e/s he s h o ul d pr o m ptl y n otif y t he dr u g s afet y 
ma na ger.   
All A Es (i ncl u di n g S A Es) are t o b e acc urat el y rec or de d o n t he A d v erse E v e nt pa ge(s) of t he 
eC R F.  T he I n v esti gat or will caref ull y e v al uate eac h A E t o deter mi ne:  
•  d urati o n (start a n d e n d dates) 
•  i nte nsit y ( gra d e) 
•  seri o us ness 
•  relati o ns hi p t o st u d y dr u g  ( U nli kel y, P ossi ble, Pr o ba ble) 
•  acti o n ta ke n wit h st u d y dr u g (st u d y dr u g m o dificati o n  or i nterr u pti o n, st u d y dr u g 
disc o nti n uati o n) 
•  acti o n ta ke n ( n o n e, me di cati o n, me dical i nter v e nti o n) 
•  o utc o me (res ol ve d wit h o ut se q uelae, res ol ve d wit h se q uelae, o n g oi n g) 
T he I n vesti gat or will e v al uate all A Es a n d S A Es wit h re gar d t o ma xi m u m i nte nsit y a n d 
relati o ns hi p t o st u d y dr u g. Ma xi m u m i nte nsit y s h o ul d be assi g n e d usi n g o ne of t he se v erit y 
gr a des as o utli ne d i n t he Nati o nal Ca ncer I nstit ute ’s C o m m o n Ter mi n ol o g y Criteria f or A d v erse 
E ve nts v 4. 0. If t he A E is n ot s pecificall y liste d i n C o m m o n Ter mi n ol o g y Criteria f or A d vers e 
E ve nts v 4. 0, t he f oll o wi n g gr a des will be use d: 
•  Gra de 1: mil d  
•  Gra de 2: m o derate 
•  Gra de 3: se v ere  
•  Gra de 4: life -t hreate ni n g or disa bli n g 
•  Gra de 5: deat h  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 2  of 8 0  
 
9. 3. 5. 7  
Deter mi ni n g Rel ati o ns hi p of A d verse E ve nts t o St u d y Dr u g  
T he I n vesti gat or m ust att e m pt t o deter mi ne if a n A E or S A E is relate d t o t he use of t he st u d y 
dr u g. T his r elati o ns hi p s h o ul d be descri be d as f oll o ws: 
Pr o b a ble  
A cli nical e ve nt, i ncl u di n g la b orat or y test a b n or malit y, wit h a reas o na bl e ti me 
se q ue nce t o a d mi nistrati o n of t he st u d y dr u g, u nli kel y t o be attri b ute d t o 
c o nc urr e nt disease or ot her dr u gs or c he micals, a n d w hic h f oll o ws a cli nicall y 
reas o na bl e res p o ns e o n wit h dra wal ( d ec halle n ge). Rec halle n ge i nf or mati o n is n ot 
re q uire d t o f ulfil t his defi niti o n. 
P ossi ble  
A cli nical e ve nt, i ncl u di n g la b orat or y test a b n or malit y, wit h a reas o na bl e ti me 
se q ue nce t o a d mi nistrati o n of t he st u d y dr u g, b ut w hic h c o ul d als o be e x plai ne d 
b y  c o n c urr e nt disease or ot her dr u gs or c h e micals. I nf or mati o n o n st u d y dr u g 
wit h dra wal ma y be l ac ki n g or u n clear.  
U nli kely  
A cli nical e ve nt, i ncl u di n g la b orat or y test a b n or malit y, wit h a te m p oral 
relati o ns hi p t o st u d y dr u g a d mi nistrati o n w hic h ma kes a ca usal rel ati o ns hi p 
i m pr o ba ble, a n d i n w hic h ot her dr u gs, c h e micals or u n derl yi n g disease pr o vi de 
pla usi ble e x pla nati o ns. 
9. 3. 5. 8  
Re p orti n g De at hs a n d Ot her Seri o us A d verse E ve nts  
9. 3. 5. 8. 1  Eve nts t o Be Re p orte d a n d Ti m efr a m e  
A n y d eat h or ot her S A E  e x perie nce d b y t he s u bject d uri n g treat me nt or wit hi n 3 0 da ys of 
recei vi n g st u d y dr u g, r e gar dless of r elati o ns hi p t o st u d y dr u g, or a n y deat h t hat occ urs m ore t ha n 
2 8 da ys after recei vi n g st u d y dr u g a n d is belie ve d t o be st u d y dr u g-relat e d, m ust be pr o m ptl y 
re p orte d t o t he S p o ns or (wit hi n 2 4 h o urs of t he I nvesti g at or bec o mi n g a w are of t he eve nt ) b y 
tele p h o ne, telef a x, or e-mail tra ns missi o n.  
9. 3. 5. 8. 2  G over ni n g Re g ul at ory Re q uire m e nts  
C o m plia nce wit h t his re q uest f or pr o m pt re p orti n g is esse ntial i n t hat t he S p o ns or is res p o nsi ble 
f or i nf or mi n g t he F D A a n d ot her re g ulat or y a ut h orities as well as all ot her partici pati n g 
I n v esti gat ors of t he e v e nt.  
U n der F D A r uli n g ( U S C o de of Fe der al Re g ulati o ns [ C F R ], Title 2 1 Part 3 1 2. 3 2) a n d t he I C H 
G ui deli nes f or Cli nical Safet y Dat a Ma na ge me nt Defi niti o ns a n d Sta n dar ds f or E x pe dite d 
Re p orti n g, t he S p o ns or is re q uire d t o s u b mit writte n d oc u me ntati o n, i n t he f or m of a n I N D 
Safet y R e p ort, o n t he f oll o wi n g: 
•  S U S A Rs  
•  Fi n di n gs fr o m ot her st u di es t hat s u g gest a si g nifi ca nt ris k t o h u ma ns e x p ose d t o dr u g 
•  Fi n di n gs fr o m a ni mal or i n vitr o testi n g t hat s u g gest a si g nifica nt  ris k t o h u ma ns e x p ose d 
t o dr u g 
•  I n crease d r ate of o cc urre nce of seri o us s us pecte d a d verse reacti o ns fr o m w hat is re porte d 
i n t he I B or t he pr ot oc ol 
Writte n s u b missi o n m ust b e ma de b y t he S p o ns or t o t he F D A/ ot her re g ulat or y a ut h orities (a n d 
b y t he I n vesti gat or t o t he I R B/I E C) as s o o n as p ossi ble, a n d i n n o e ve nt later t ha n 1 5 c ale n d ar 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 3  of 8 0  
 
d a ys  after t he S p o ns or deter mi nes t hat t he i nf or mati o n q ualifies f or re p orti n g. T he S p o ns or s h all 
als o i nf or m all I n vesti gat ors. 
I n a d diti o n, t he S p o ns or is f urt her r e q uire d t o re p ort, b y eit her tele p h o n e or facsi mile 
tra ns missi o n or i n writi n g t o t he F D A/ ot her re g ul at or y a ut h orities t he occ urre nce of a n y 
u ne x pecte d fatal or lif e -t hreate ni n g e v ent ass ociat e d wit h t he use of t he dr u g ( S U S A Rs) n o later 
t ha n 7 c ale n d ar d a ys  after n otificati o n of t he e ve nt, f oll o we d b y a writte n re p ort n o l ater t h a n 
1 5 c ale n d ar d a ys  after t he i nitial re p ort recei pt d ate. T he S p o ns or s hall als o i nf or m all 
I n v esti gat ors. 
T he S p o ns or will pr o vi de e x pe dite d re p orts of t he f oll o wi n g S U S A Rs t o t he I n vesti gat or s f or 
re p orti n g t o t heir I R B/I E C: 
•  S U S A Rs t hat ha ve arise n i n t he cli nical tri al t hat was assesse d b y t h e I R B /I E C 
•  S U S A Rs t hat ha ve arise n i n ot her cli nical trials of t h e sa me S p o ns or a n d wit h t he sa me 
me dici nal pr o d uct, a n d t h at c o ul d ha ve c o nse q ue n ces f or t he s afet y of t he s u bjects 
i n v ol ve d i n t he cli nical trial t hat was assesse d b y t he I R B /I E C 
I n v esti gat ors ar e re q uir e d t o pr o m ptl y re p ort t o t he I R B/I E C all u na ntici pat e d pr o ble ms 
i n v ol vi n g ris k t o h u ma n s u bjects, i ncl u di n g A Es t h at s h o ul d be c o nsi dere d u na ntici pate d 
pr o ble ms ( 2 1 C F R 3 1 2. 5 3(c)( 1)( vii), 3 1 2. 6 6, a n d 2 1 C F R 5 6. 1 0 8( b)( 1)). 
9. 3. 5. 9  
I niti al I nf or m ati o n Pr o vi de d b y t he I n vesti g at or 
T he I n vesti gat or m ust tra ns mit s ufficie nt i nitial i nf or mati o n t o t he S p o ns or ( or desi g n ee) s h o ul d 
a n S A E re p ort meet t he criteria f or c o m pleti o n of a n I N D Safet y Re p ort. As m uc h of t he 
f oll o wi n g i nf or mati o n a b o ut t he s u bject a n d t he e v e nt will be re q ueste d:  
•  S u bject  i de ntificati o n c o de, ge n der, a n d a ge or date of birt h 
•  U n derl yi n g dia g n osis a n d e xte nt of disease 
•  L ot n u m ber a n d e x pirati o n da te of st u d y dr u g (if a vaila ble) 
•  D ose, r o ute, fre q ue n c y, a n d d urati o n of st u d y dr u g a d mi nistere d 
•  Date of last st u d y dr u g a d mi nistrati o n 
•  Descri pti o n of e v e nt, i ncl u di n g date of o nset a n d d urati o n 
•  Date of deat h (if a p plica ble)  
•  I nter ve nti o n(s) re q uire d 
•  C o nc o mita nt t hera p y (i ncl u di n g re gi me ns a n d i n dicati o ns) 
•  Perti ne nt la b orat or y dat a/ dia g n ostic st u d y (i ncl u di n g dat es) 
•  Perti ne nt me dical hist or y  
•  St u d y dr u g stat us ( d ose i nterr u pte d, disc o nti n ue d) 
•  Di d e ve nt a bat e after i nterr u pti o n of st u d y dr u g a d mi nistrati o n (if a p plica ble)?  
•  Di d e ve nt rec ur after st u d y dr u g was rei ntr o d uce d (if a p plica ble)? 
•  Se verit y of t he A E  
•  Relati o ns h i p of t he A E t o st u d y dr u g  
•  O u tc o me of t he A E 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 4  of 8 0  
 
9. 3. 5. 1 0  F o ll o w- u p I nf or m ati o n  
F oll o w- u p data c o ncer ni n g t he S A E ( e. g., dia g n ostic test re p orts, p h ysi cia n's s u m maries, etc.) 
m ust als o be s u b mitte d t o t he S p o ns or as t he y bec o me a vaila ble, prefera bl y b y telefa x or e -mail, 
as s o o n as t he y bec o me a vaila ble, a n d u ntil t he e v e nt res ol ves or sta bilizes. 
9. 3. 5. 1 1  Seri o us A d verse E ve nt a n d Seri o us a n d U ne x pecte d S us pecte d A d verse Re acti o n  
Re vie w a n d P ote nti al I m p act o n Tri al C o n d uct 
T he I n vesti gat or will re vi e w eac h S A E re p ort a n d e val uate f urt her t he relati o ns hi p of t he S A E t o 
st ud y dr u g a n d t o t he s u bject’s u n derl yi n g diseas e. 
Base d o n t h e I n vesti gat or’s a n d S p o ns or’s assess m e nt of ca us alit y of t he A E  a n d disc ussi o ns 
wit h t he me dical m o nit or , a decisi o n will be ma de b y t he S p o ns or c o n cer ni n g t he n ee d f or f urt her 
acti o n wit h res pect t o t he f ut ure c o n d u ct of t he st u d y. T he pri mar y c o nsi d erati o n g o ver ni n g 
f urt her acti o n is w het her ne w fi n di n gs affect t he s afet y of ot her s u bjects partici pati n g i n t he 
cli nical st u d y.  If t he disc o ver y of a n e w A E relate d t o st u d y dr u g raises c o ncer n o ver t he safet y 
of its c o nti n ue d a d mi nistrati o n t o s u bjects, t he S p o ns or will ta ke i m me diate ste ps t o n otif y t he 
F D A, ot her re g ulat or y a ut h orities, a n d all I n v esti gat or s partici pati n g i n cli nical st u dies wit h t he 
st u d y dr u g. 
F urt her acti o n re q uire d ma y i ncl u d e a n y of t he f oll o wi n g: 
•  Alterati o n of t he e xisti n g researc h pr o gra m b y m o dificati o n of  t he pr ot oc ol 
•  Disc o nti n uati o n or s us pe nsi o n of t he st u d y 
•  Alterati o n of t he i nf or m e d c o nse nt pr ocess b y m o dificati o n of t he e xisti n g I nf or me d 
C o nse nt F or m (I C F) a n d i nf or mi n g c urre nt st u d y partici pa nts of ne w fi n di n gs 
•  M o dificati o n of pre vi o usl y i de ntifie d e x pecte d s us pecte d a d v erse reacti o n lists t o i ncl u de 
A Es ne wl y i de ntifie d as st u d y dr u g- relate d 
9. 4  
Ti mi n g of Assess me nts  
9. 4. 1  
Scree ni n g  Peri o d  
9. 4. 1. 1  
Visit 1  
•  I nf or me d c o ns e nt 
•  I n cl usi o n/ E x cl usi o n criteria 
•  De m o gra p hics 
•  Me dical/ S ur gi cal hist or y  
•  P h ysical  e x a mi nati o n  
•  U P OI N T  classificati o n  
•  NI H -C P SI  
•  Pa per - bas e d 1 1- p oi nt N R S 
•  P C S  
•  P H Q - 9 
•  1 2- lea d s u pi ne E C G  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 5  of 8 0  
 
•  V ital si g ns (H R, B P , te m perat ure) 
•  Hei g ht  
•  Wei g ht  
•  Cli nical c he mistr y  ( d o es n ot nee d t o be fasti n g), h e mat ol o g y, uri n al ysis 
•  Uri ne: bacterial c ult ure & se nsiti vit y, le u k o c yt e esterase test  
•  A E c ollecti o n  
•  Re vie w c o nc o mita nt me dicati o n  
•  e Diar y iss ue/trai n  
9. 4. 1. 2  
B aseli ne O p ht h al mic T esti n g ( Visit 1 a)  
O p ht hal mic assess me nt  at Visit 1a ma y occ ur at a n y ti me d uri n g t he Scree ni n g peri o d. 
O p ht hal mic assess me nts i ncl u de :  
•  B C V A usi n g t he L o g M A R c hart (i.e. after ma nifest refracti o n)  
•  I O P ( pref er a bl y m eas ur e d b y G ol d ma nn t o n o metr y bef ore a n d aft er dilati o n wit h 
m y driatic a ge nt ) 
•  C or neal stai ni n g 
•  Slit la m p e x a mi nati o n  
•  Le ntic ul ar o pacificati o n usi n g L O C S III   
9. 4. 2  
B aseli ne ( Visit 2)  
•  NI H -C P SI  
•  Pa per - bas e d 1 1- p oi nt N R S 
•  P H Q - 9 
•  II E F 
•  P GI - S 
•  Re vie w I ncl usi o n/ E x cl usi o n criteria  
•  e Diar y r e vie w f or I ncl usi o n/ E x cl usi o n criteria  
•  P h ysical e x a mi nati o n  
•  V ital si g ns ( H R, B P, te m perat ure) 
•  Cli nical c he mistr y  ( d o es n ot nee d t o be fasti n g), h e mat ol o g y, uri n al ysis  
•  V oi di n g fr e q ue n c y meas ure d o ver a 2 4- h o ur p eri o d, wit hi n a 3- da y ( 7 2 h o urs) wi n d o w 
bef ore t h e sc he d ule d Visit  
•  A E c ollecti o n  
•  Re vie w co nc o mita nt me dicati o n  
•  Ra n d o mizati o n after c o nfir mi n g s u bject c o nti n ues t o meet eli gi bilit y criteria 
•  St u d y dr u g dis pe nsi n g  
•  A d mi nistrati o n of first d ose of st u d y dr u g (after all assess me nts perf or me d) 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 6  of 8 0  
 
9. 4. 3  
Tre at m e nt Peri o d  
9. 4. 3. 1  
Visit 3  
•  NI H -C P SI  
•  Pa per - bas e d 1 1- p oi nt N R S 
•  P H Q - 9 
•  G R A  
•  P GI - C 
•  II E F 
•  P GI - S 
•  V oi di n g fr e q ue n c y meas ure d o ver a 2 4- h o ur p eri o d, wit hi n a 3- da y ( 7 2 h o urs) wi n d o w 
bef ore t h e sc he d ule d visit 
•  Vital si g ns ( H R, B P , te m perat ure) 
•  A E c ollecti o n  
•  Re vie w c o nc o mita nt me dicati o n  
•  St u d y dr u g dis pe nsi n g 
•  St u d y dr u g c o m plia nce c hec k  
•  St u d y dr u g acc o u nta bilit y  
•  e Diar y r e vie w  
9. 4. 3. 2  
Visit 4  
•  NI H -C P SI  
•  Pa per - bas e d 1 1- p oi nt N R S  
•  P H Q - 9 
•  G R A  
•  P GI - C 
•  II E F  
•  P GI - S 
•  V oi di n g fr e q ue n c y meas ure d o ver a 2 4- h o ur p eri o d, wit hi n a 3- da y ( 7 2 h o urs) wi n d o w 
bef ore t h e sc he d ule d visit 
•  P h ysical e x a mi nati o n  
•  O p ht hal mic assess me nts ( B C V A, I O P, c or neal stai ni n g, slit la mp, L O C S III)   
•  1 2-lea d s u pi ne E C G 
•  Vital si g ns ( H R, B P , te m perat ure) 
•  Wei g ht  
•  Cli nical c he mistr y ( d o es n ot nee d t o be fasti n g), h e mat ol o g y, uri n al ysis 
•  A E c ollecti o n  
•  Re vie w c o nc o mita nt me dicati o n  
•  St u d y dr u g c o m plia nce c hec k  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 7  of 8 0  
 
•  St u d y dr u g acc o u nta bilit y  
•  e Diar y r e vie w  
9. 4. 4  
E arly Ter mi n ati o n 
•  NI H -C P SI  
•  Pa per - bas e d 1 1- p oi nt N R S 
•  P H Q - 9 
•  G R A  
•  P GI - C 
•  II E F  
•  P GI - S 
•  V oi di n g fr e q ue n c y meas ure d o ver a 2 4- h o ur p eri o d, wit hi n a 3- da y ( 7 2 h o urs) wi n d o w 
bef ore t h e sc he d ule d visit 
•  P h ysical e x a mi nati o n  
•  O p ht hal mic asses s me nts (B C V A, I O P, c or neal stai ni n g, slit la m p, L O C S III)  
•  1 2-lea d s u pi ne E C G   
•  Vital si g ns ( H R, B P , te m perat ure) 
•  Wei g ht  
•  Cli nical c he mistr y ( d o es n ot nee d t o be fasti n g), h e mat ol o g y, uri n al ysis   
•  A E c ollecti o n  
•  Re vie w c o nc o mita nt me dicati o n  
•  St u d y dr u g c o m plia nce c hec k  
•  St u d y dr u g acc o u nta bilit y  
•  e Diar y r e vie w  
9. 4. 5  
S afety F oll o w- u p  
9. 4. 5. 1  
Off - Tre at me nt S af et y F oll o w -u p  
•  NI H -C P SI  
•  Pa per - bas e d 1 1- p oi nt N R S 
•  P H Q - 9 
•  G R A  
•  P GI - C 
•  II E F  
•  P GI - S 
•  V oi di n g fr e q ue n c y meas ure d o ver a 2 4- h o ur p eri o d, wit hi n a 3- da y ( 7 2 h o urs) wi n d o w 
bef ore  t h e sc he d ule d visit 
•  P h ysical e x a mi nati o n ( o nl y nee de d if t here are o utsta n di n g safet y c o ncer ns fr o m Wee k 
1 2) 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 8  of 8 0  
 
•  O p ht hal mic assess me nts ( o nl y nee de d if t h ere are o utsta n di n g safet y c o ncer ns fr o m Wee k 
1 2) 
•  1 2-lea d s u pi ne E C G ( o nl y nee de d if t here are o utsta n di n g safet y c o n cer ns fr o m Wee k 1 2)  
•  Vital si g ns ( H R, B P , te m perat ure) 
•  Wei g ht  
•  Cli nical c he mistr y ( d o es n ot nee d t o be fasti n g), h e mat ol o g y, uri n al ysis ( o nl y nee de d if 
t here are o utsta n di n g saf et y c o ncer ns fr o m Wee k 1 2) 
•  A E c ollecti o n  
•  Re vie w c o nc o mita nt me dicati o n 
•  e Diar y r e vie w/c ollect  
9. 4. 5. 2  
Tele p h o ne C all  
•  A E c ollecti o n  ( o p ht hal mic relate d A Es o nl y) 
9. 4. 5. 3  
O p ht h al mic  
•  O p ht hal mic assess me nts  
•  A E c ollecti o n  ( o p ht hal mic relate d A Es o nl y) 
9. 4. 5. 4  
U nsc he d ule d Visit  
U nsc he d ule d visits ma y be c o n d ucte d at a n y ti me d uri n g t he st u d y a n d m a y  i ncl u de t h e sa me 
assess me nts as Wee k 1 2 ( Visit 4 ). 
1 0  
S T A TI S TI C A L M E T H O D S A N D P L A N N E D A N A L Y S E S  
S tatistical met h o d s a n d c o n ve nti o ns are des cri be d  i n t his secti o n. F ull details o n t he a nal ysis 
met h o ds a n d prese ntati o n of st u d y r es ults will be pr o vi de d i n t he s tatistical a nal ysis pla n ( S A P). 
T he S A P will be fi nalize d pri or t o u n bli n di n g of t he trial . 
1 0. 1  
Ge ner al C o nsi der ati o ns  
All statistical a nal yses will be perf or me d usi n g S A S  Versi o n 9. 4 or hi g her. 
All cli nical st u d y data will be prese nte d i n s u bject data listi n gs. Descri pti ve statistics ( n, mea n, 
sta n dar d de viati o n, me di a n, mi ni m u m, a n d ma xi m u m) will be calc ulate d b y treat me nt gr o u p f or 
c o nti n u o us varia bles. C o nfi de nce i nter vals ( CIs) will be pr o vi de d w here a p pr o priate. 
Fre q u e ncies a n d per ce nta ges will be prese n te d b y treat me nt gr o u p f or cate g orical a n d or di n al 
varia bles.  
Mea ns, me dia ns, a n d CIs  will be re p orte d t o 1 deci mal place m ore t ha n t h e data re p orte d o n t he 
e C R F or b y t he la b or at or y/ ve n d or. Sta n dar d de vi ati o ns will be re p orte d t o 2 deci mal places m ore 
t ha n t he data r e p orte d. Mi ni m u m a n d ma xi m u m will be re p orte d t o t he sa m e n u m ber of d eci mal 
places dis pla ye d o n t he e C R F or b y t h e la b orat or y/ ve n d or. P  val ues will be re p orte d t o 4 deci mal 
places.  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 4 9  of 8 0  
 
1 0. 2  
S a m ple Size D eter mi n ati o n   
Sa m ple size was calc ulat e d usi n g t he 2- sa m ple mea ns state me nt i n t he P O W E R pr oce d ure i n 
S A S. A sa m ple size of 4 5 s u bjects per treat me nt gr o u p will pr o vi de 8 0 % p o wer t o detect a 1. 2-
p oi nt differe nce i n t he c h a n ge fr o m Bas eli ne  ma xi m u m pel vic pai n sc ore b et wee n A Q X - 1 1 2 5 
a n d place b o ass u mi n g a bet wee n -s u bj ect sta n dar d de viati o n of 2. 0 a n d a 2-si de d 5 % si g nifica nce 
le vel.  
Ass u mi n g a 1 0 % rate of disc o nti n uati o n fr o m st u d y dr u g, t h e t otal n u m ber of s u bjects t o be 
ra n d o mize d is a p pr o xi matel y 1 0 0. Su bjects w h o  disc o nti n ue will be i ncl u de d i n t he pri mar y 
a nal ysis, res ulti n g i n a sli g ht decrease i n p o wer if t he disc o nti n ui n g s u bjects i n t he place b o gr o u p 
ha ve n o a d diti o nal c h a n ge after disc o nti n uati o n of st u d y dr u g w hile t he dis c o nti n ui n g s u bjects i n 
the A Q X - 1 1 2 5 gr o u p h a ve a l oss of efficac y aft er disc o nti n ui n g st u d y dr u g. 
1 0. 3  
St u d y P o p ul ati o ns  
T he f oll o wi n g are t h e a n al ysis p o p ulati o ns t o be use d: 
•  I nte nt-t o- Treat (I T T) P o p ulati o n: T he I T T P o p ulati o n will i ncl u de all ra n d o mize d s u bjects . I n 
t he e ve nt of st u d y dr u g a d mi nistrati o n err or, a nal yses o n t he I T T P o p ulati o n will be 
perf or me d acc or di n g t o t he treat me nt t o w hic h t he s u bject was ra n d o mize d t o recei ve.  
•  Safet y P o p ulati o n: T he S afet y P o p ulati o n will i ncl u de all s u bjects w h o recei ve d a n y a m o u nt 
of st u d y dr u g. I n t he e v e nt of st u d y dr u g a d mi nistrati o n err or, a nal yses o n t he Safet y 
P o p ulati o n will be perf or me d acc or di n g t o t he treat me nt t he s u bject act uall y recei v e d . 
•  Per -Pr ot oc ol ( P P) P o p ulati o n : T he P P P o p ulati o n will i ncl u de all I T T s u bjects w h o d o n ot 
ha ve a n y maj or  pr ot oc ol de viati o ns a n d ha ve n o n-missi n g Bas eli ne  a n d Wee k  1 2 assess me nts 
of ma xi m u m dail y pel vic pai n  (i.e. t he pri mar y efficac y ass ess me nt). I n t he e ve nt of st u d y 
dr u g a d mi nistrati o n err or, a nal ys es o n t he P P  P o p ulati o n will be perf or me d a cc or di n g t o t he 
treat me nt t he s u bject act uall y r ecei v e d . 
1 0. 4  
St atistic al A n al yses 
1 0. 4. 1  
S u bject  Acc o u nt a bility, De m o gr a p hics, a n d B aseli ne C h ar acteristics 
S u bject  dis p ositi o n (e nr oll me nt, ra n d o mizati o n, st u d y c o m pleti o n) a n d reas o ns f or n ot 
c o m pleti n g t he st u d y will  be prese nt e d b y treat me nt gr o u p a n d o verall. A d diti o nall y, t h e n u m ber 
of s u bjects i n eac h of t he a nal ysis p o p ulati o ns ( S e cti o n 1 0. 3 ) will be pres e nte d b y treat me nt 
gr o u p a n d o ver all. 
S u bject de m o gr a p hics a n d b aseli ne c haracteristics will be s u m marize d b y treat me nt gr o u p a n d 
o verall  f or t he I T T, Saf et y, a n d P P P o p ulati o ns. Descri pti ve statistics will be pr o vi de d f or a ge, 
hei g ht, a n d wei g ht. Fr e q ue ncies a n d p erce nta ges will be ta b ulate d f or se x, race, a n d et h nicit y.  
1 0. 4. 2  
Effic acy D at a  
T he pri mar y efficac y a n al ysis p o p ulati o n will be t he I T T P o p ulati o n. Se nsiti vit y a nal ysis f or 
selecte d e n d p oi nt a n al yses will be perf or me d o n t h e P P P o p ulati o n.  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 0  of 8 0  
 
1 0. 4. 2. 1  Wee k l y Sc ores b ase d o n D ail y Assess me nts  
F or w ee kl y sc or es t hat ar e base d o n dail y s u bject assess me nts (e. g., ma xi m u m dail y pel vic sc ore 
rec or d e d dail y b y t he  e Diar y) a s u bject’s sc ore f or a wee k will be t he a vera ge ( mea n) of t he dail y 
sc ores acr oss t hat wee k.  
1 0. 4. 2. 2  Pri m ar y Effic ac y E n d p oi nt 
T he pri mar y e n d p oi nt is t he c ha n ge fr o m Baseli ne  (Visit  2) t o Wee k  1 2 (Visit  4) i n t he ma xi m u m 
dail y pel vic p ai n ( mea n)  usi n g a sta n d ar dize d 1 1- p oi nt N R S pai n sc ore rec or de d dail y b y a n 
e Diar y. 
1 0. 4. 2. 3  Pri m ar y Effic ac y E n d p oi nt A n al ysis 
C o m paris o n of A Q X - 1 1 2 5 t o place b o at Wee k 1 2 f or t he pri mar y effi cac y e n d p oi nt will use 
mi x e d m o del re peate d meas ures ( M M R M) a nal ysis of c o varia n ce  ( A N C O V A) t o c o m pare 
c ha n ge fr o m Baseli ne  i n N R S sc ore ( de p e n de nt varia ble) bet w ee n treat me nt ar ms (A Q X - 1 1 2 5 
a n d place b o). T he m o del will i ncl u de t he Wee ks 6 a n d 1 2 c ha n ge fr o m bas eli ne sc ores f or eac h 
s u bject. T he M M R M m o del will ha ve fact ors f or Visit, Visit × Treat me nt  i nteracti o n, a n d a 
Visit × B aseli ne i nteracti o n c o variate. T he treat me nt effects  f or eac h gr o u p a n d t he treat me nt 
gr o u p differ e nce will be esti mate d b y least -sq uares mea ns  f or Wee k  1 2 a n d teste d at t he 2 -si de d 
0. 0 5 le vel. 
T he least -s q uares mea ns treat me nt gr o u p esti mates a n d t he differe nce bet w ee n treat me nt gr o u ps 
will be prese nte d f or all Wee ks 1  t hr o u g h 1 2 wit h c orres p o n di n g c o nfi de nce i nter vals. 
1 0. 4. 2. 4  Sec o n d ar y Effic ac y E n d p oi nts 
T he sec o n d ar y efficac y e n d p oi nts are: 
•  T he c ha n ge fr o m Baseli n e  t o Wee k 1 2 f or eac h of t he f oll o wi n g:  
o  NI H - C P SI p ai n s u bscale a n d all d o mai ns t otal sc ore 
o  Male se x ual healt h as meas ure d usi n g t he II E F- E F  
o  Mea n of a v era ge dail y pel vic pai n sc ores (e D iar y), a vera ge a n d ma xi m u m dail y 
pel vic pai n ( pa p er -b ase d N R S i n cli nic) 
o  2 4- h o ur v oi di n g fre q u e nc y (e Diar y) 
•  Ti me c o urse of eff ects: A Q X - 1 1 2 5 ( 2 0 0 m g o nce- dail y) c o m pare d t o place b o o n the 
c ha n ge fr o m Baseli ne  (Visit  2) t o Wee k  6 (Visit  3), Wee k  1 2 (Visit  4), a n d Wee k  1 6 (i.e. 
4 wee ks after e n d of treat me nt) f or eac h of t h e f oll o wi n g:  
o  Mea n of m axi m u m dail y pel vic pai n  sc ore (e Di ar y) 
o  NI H -C P SI p ai n s u bscale a n d all d o mai ns t otal sc ore  
o  II E F-E F  
o  Mea n of a v era ge dail y pel vic pai n sc ores (e D iar y), a vera ge a n d ma xi m u m pel vic pai n 
( Pa per-b ase d N R S i n cli nic).  
o  2 4- h o ur v oi di n g fre q u e nc y (e Diar y) 
•  Res p o nse t o treat me nt as meas ure d b y t he G R A , PGI - C, a n d P GI- S at Wee k  1 2 (Visit  4).  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 1  of 8 0  
 
•  A ≥3 0 % a n d ≥5 0 % i m pr o ve me nt i n ma xi m u m dail y pel vic pai n ( usi n g t he 1 1- p oi nt N R S 
rec or d e d b y e Di ar y a n d t he NI H- C P SI pai n s u bscale) c o m pare d t o place b o, at W ee k 6 
( Visit 3) a n d Wee k 1 2 ( Visit 4). 
•  Res p o n der a n al ysis: Res p o nse t o treat me nt defi n e d b y a n y of t he f oll o wi n g: 
o  Decr ease i n ma xi m u m dail y pel vic pai n fr o m Baseli ne t o Wee k 1 2 (e Diar y) wit h n o 
c ha n ge i n t he a m o u nt or stre n gt h of c o nc o mita nt a nal gesic me dicati o ns 
o  Decr ease i n ma xi m u m dail y pel vic pai n fr o m Baseli ne t o Wee k 1 2 (e Diar y) wit h a 
decrease i n t he a m o u nt or stre n gt h of c o n c o mita nt a nal gesic me dicati o ns 
•  Disc o nti n uati o n of st u d y me dicati o n d ue t o treat m e nt fail ure ( % meeti n g treat me nt fail ure 
criteria a n d ti me t o e ve nt)  
 
1 0. 4. 2. 5  Sec o n d ar y Effic ac y E n d p oi nts A n al yse s 
F or t he f oll o wi n g dic h ot o m o us sec o n dar y efficac y e n d p oi nts, t he rates f or eac h treat me nt gr o u p 
a n d t he differe nce bet w ee n t he treat me nt gr o u ps will be prese nte d wit h c orres p o n di n g 9 5 % CIs. 
A C oc hra n – Ma nt el – Hae nszel test will be use d t o test f or differe nces i n rat es bet wee n t h e 
treat me nt gr o u ps c o ntr olli n g f or b aseli ne pel vic p ai n. 
•  Treat me nt r es p o nse  as d efi ne d b y m eeti n g eit her of t he f oll o wi n g:  
o  Decr ease i n ma xi m u m dail y pel vic pai n fr o m Baseli ne  t o Wee k 1 2 usi n g a 
sta n dar dize d 1 1- p oi nt N R S wit h n o c ha n ge i n t he a m o u nt or stre n gt h of c o nc o mita nt 
a nal gesic me dicati o ns  
o  Decr ease i n ma xi m u m dail y pel vic pai n fr o m Baseli ne  t o Wee k 1 2 usi n g a 
sta n dar dize d 1 1- p oi nt N R S wit h a decreas e i n t he a m o u nt or stre n gt h of c o nc o mita nt 
a nal gesic me dicati o ns  
•  A ≥3 0 % a n d ≥5 0 % i m pr o ve me nt i n ma xi m u m dail y pel vic pai n ( usi n g t he 1 1- p oi nt N R S 
rec or d e d b y e Di ar y a n d t he NI H- C P SI pai n s u bscale), at Wee k s 6 ( Visit 3) a n d 1 2 ( Visit 
4).  
•  Disc o nti n uati o n of st u d y me dicati o n d ue t o treat m e nt fail ure ( % meeti n g treat me nt fail ure 
criteria a n d ti me t o e ve nt)  
 
T he f oll o wi n g c ha n ge fr o m Baseli ne  t o Wee k  1 2 e n d p oi nts will be a nal yz e d i n a ma n ner si milar 
t o t he pri mar y efficac y a nal ysis as d escri be d i n S e cti o n 1 0. 4. 2. 3 . 
•  NI H - C P SI p ai n s u bscale a n d all d o mai ns t otal sc ore.  
•  Male se x ual healt h as meas ure d usi n g t he II E F -E F.  
•  Mea n of a v era ge dail y pel vic pai n sc ores (e Diar y), dail y pel vic p ai n (i n cli nic), a n d 
ma xi m u m dail y pel vic pai n (i n cli nic).  
•  2 4- h o ur v oi di n g fre q u e nc y 
A d diti o nall y, f or t he II E F- E F d o mai n e n d p oi nt, t he fre q u e nc y distri b uti o n of t he 5 cate g or y 
II E F-E F s c ore (i.e. des cri be d i n  A p p e n di x 5. I nt er n ati o n al I n d e x of Er e ctil e F u n cti o n 
Q u esti o n n air e ) will be prese nte d b y tr eat me nt gr o u p f or Wee k 1 2 as w ell as a s hift ta ble fr o m 
Baseli ne . Treat me nt gr o u p differe n ce i n t he 5-cate g or y II E F-E F will be ass esse d b y a C oc hra n -
Ma ntel -Hae nszel ( C M H) test c o ntr olli n g f or Bas eli ne  II E F-E F sc ore.  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 2  of 8 0  
 
T he f oll o wi n g ti me c o urs e sec o n dar y e n d p oi nts will be assesse d b y M M R M A N C O V A m o del 
w here t he c ha n ge fr o m Baseli ne  is t he de pe n d e nt varia ble a n d li near tre n ds acr oss ti me (i.e., 
visit) are assess e d.  
Ti me c o urse of eff ects: A Q X - 1 1 2 5 ( 2 0 0 m g o nce- dail y) c o m pare d t o place b o o n the c ha n ge fr o m 
Baseli ne ( Visit 2) t o Wee k 6 ( Visit 3), Wee k 1 2 ( Visit 4) a n d Wee k 1 6 (i.e. 4 wee ks after e n d of 
treat me nt) f or eac h of t he f oll o wi n g:  
•  Mea n of ma xi m u m dail y pel vic pai n sc ore (e Di ar y).  
•  NI H - C P SI p ai n s u bscale a n d all d o mai ns t otal sc ore.  
•  II E F-E F.  
•  Mea n of a v era ge dail y pel vic pai n sc ores (e Diar y), dail y pel vic p ai n (i n cli nic), a n d 
ma xi m u m dail y pel vic pai n (i n cli nic).  
•  2 4- h o ur v oi di n g fre q u e nc y.  
F or t he f oll o wi n g sec o n d ar y e n d p oi nts, t he fre q ue nc y distri b uti o n of eac h res p o nse scale will be 
prese nte d b y tr eat me nt gr o u p. F or t he G R A a n d P GI- C, treat me nt gr o u p differe nces will be 
assesse d b y mea ns of a c hi -s q uare test. F or t he P GI-S, treat me nt differe nces will be assesse d b y 
mea ns of a C M H test c o ntr olli n g f or Baseli ne  P GI - S.  
•  Res p o nse t o t reat me nt as meas ure d b y t he G R A , P GI- C, P GI- S at Wee k 1 2 ( Visit  4).  
1 0. 4. 2. 6  C o ntr ol f or M ulti plicit y  
T he T y pe 1 err or rate f or t he pri mar y e n d p oi nt a n al ysis is at t he 0. 0 5 le vel ( 2-si de d). T he T y p e I 
err or rate will n ot be c o ntr olle d f or t he sec o n dar y efficac y e n d p oi nts.  
1 0. 4. 2. 7  I nteri m a n al yses 
T here are n o i nteri m a nal ys es pla n n e d f or t his trial.  
1 0. 4. 3  
S afety D at a  
Safet y a nal yses will be base d o n t he Safet y P o p ul ati o n. Safet y d ata will be prese nte d b y 
treat me nt gr o u ps. Des cri ptive statistics will be prese nte d; i nfere ntial  statistical tests  will n ot be 
perf or me d.  
T he safet y assess me nts i ncl u de A Es, cli nical la b orat or y tests, p h ysical e x a mi nati o n, vital si g ns, 
a n d E C G assess me nts . C ha n ge fr o m Bas eli ne  will be s u m marize d f or safet y la b orat or y tests, 
vital si g ns, a n d E C G assess me nts. S hif t ta bles f or t he la b tests ( hi g h, l o w or n or mal) will als o be 
prese nte d.  
All A Es will be classifie d acc or di n g t o t he M e d D R A dicti o nar y. A Es will be s u m marize d b y t he 
n u m ber a n d perce nt a ge of s u bjects e x perie nci n g a n y A E, a n y S A E, a n d a n y A E lea di n g t o st u d y 
disc o nti n uati o n d uri n g t h e treat me nt peri o d. A Es will als o be s u m marize d b y 1) S yste m Or ga n 
Class  ( S O C) a n d Preferre d Ter m  ( P T); 2) S O C , PT,  a n d se verit y; a n d 3) S O C , P T, a n d 
relati o ns hi p t o st u d y dr u g.  
O p ht hal mic safet y  will b e s u m marize d b y treat me nt gr o u ps i ncl u di n g: assess me nt of le ntic ular 
o p acificati o n usi n g L O C S III, B C V A usi n g t he L o g M A R  c h art, I O P, c or n eal stai ni n g, a n d slit 
la m p e x a mi nati o n at Baseli ne a n d 6 m o nt hs p ost last d ose, a n d at E T. 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 3  of 8 0  
 
1 1  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  
Q ualit y Ass ur a nce ( Q A) a n d Q ualit y C o ntr ol s yst e ms will be i m ple me nte d a n d mai ntai ne d wit h 
Sta n dar d O per ati n g P r o ce d ures, as a p pr o pri ate, t o e ns ure t hat t his cli nical st u d y is c o n d ucte d a n d 
data  ar e ge nerate d, d o c u me nte d a n d re p orte d i n c o m plia nce wit h t he pr ot o c ol, I C H E 6 G C P , a n d 
a p plica ble r e g ulat or y r e q uire me nt s. 
Bef ore e nr olli n g a n y s u bject s i n t his st u d y, a S p o ns or re prese ntati ve a n d t h e I n vesti gat or will 
re vie w t he pr ot oc ol, I B, e C R Fs a n d i nstr ucti o ns f or t heir c o m pleti o n, as well as t he pr oce d ures 
f or o btai ni n g i nf or me d c o nse nt a n d f or re p orti n g A Es a n d S A Es. A q ualifi e d re prese ntati ve of 
t he S p o ns or will m o nit or t he c o n d uct of t he st u d y b y visiti n g t he site a n d b y c o nt acti n g t he site 
b y tele p h o n e a n d e mail. D uri n g site visits, t he st u d y m o nit or will ass ure acc urate a n d relia ble 
data c ollecti o n b y verif yi n g t he i nf or mati o n rec or de d o n t he e C R Fs a gai nst s o urce d oc u m e nts 
a n d me dical r ec or ds (i.e.  s o urce d oc u m e nt verificati o n).  
Meas ures will be u n d erta ke n t o pr o tect t he c o nfi de ntialit y of rec or ds t hat c o ul d i de ntif y s u bjects 
res pecti n g t he pri v ac y a n d c o nfi de ntialit y r ules i n acc or d a nce wit h a p plica ble re g ulat or y 
re q uire me nts. 
1 2  
D O C U M E N T A TI O N A N D I N S P E C TI O N S  
1 2. 1  
St u d y M o nit ori n g  
T he S p o ns or has res p o nsi bilit y t o g o ver ni n g re g ul at or y a ut h orities t o ta ke all reas o na ble ste ps t o 
e ns ure t he pr o per c o n d uct of t he st u d y wit h res p ect t o trial et hics, pr ot oc ol a d here n ce, a n d data 
i nte grit y a n d v ali dit y. 
T his trial will be cl osel y m o nit ore d b y S p o ns or re prese ntati ves t hr o u g h o ut its d urati o n. 
M o nit ori n g will be i n t he f or m of pers o n al visits wit h t he I n v esti gat or a n d staff as w ell as a n y 
a p pr o priate c o m m u nicati o ns b y tele p h o n e, telefa x, mail, or e -mail tra ns missi o n. T he p ur p ose of 
t hese c o ntacts is t o re vi e w trial pr o gress, I n v esti gat or a n d s u bject a d here nce t o t he pr ot oc ol, a n d 
t o deter mi ne if t her e ar e a n y pr o ble ms ass ociat e d wit h t he c o n d uct of t he st u d y. T he f oll o wi n g 
ma y b e assesse d d uri n g site m o nit ori n g visits:  
•  Re q uire d re g ulat or y d oc u me ntati o n 
•  Si g ne d I C Fs 
•  S u bject  accr u al an d f oll o w- u p 
•  St u d y dr u g i n ve nt or y r ec or ds 
•  I n v esti gat or a n d s u bject c o m plia nce t o t he st u d y pr ot oc ol 
•  C o nc o mita nt me dicati o n use 
•  A E  d oc u me ntati o n 
•  Pr ot oc ol de viati o n d oc u me ntati o n 
•  Data ar e  acc ur ate, c o m pl ete, a n d verifia ble w h e n c o m pare d t o s o urce d oc u me nts 
T he I n vesti gat or a n d st u d y staff ar e e x pecte d t o c o o perate wit h m o nit ors d uri n g s uc h visits a n d 
pr o vi de all rele v a nt st u d y d oc u me nts. 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 4  of 8 0  
 
1 2. 2  
A u dits a n d I ns pecti o ns  
All d oc u me ntati o n pertai ni n g t o t his cli nical trial ma y b e s u bject t o a Q A a u dit b y t he S p o ns or, 
or Re g ul at or y A ut h orities (e. g., t he F D A). U p o n re q uest, t he a u dit or will h a ve access t o i ns pect, 
c o p y, re vie w, a n d a u dit all s o urce d oc u me nts, e C R Fs, me dical rec or ds, c orres p o n de n ce, a n d 
I C Fs pertai ni n g t o t he s u bjects i n t he trial. T he I n vesti gat or a grees t o pr o m ptl y ta ke a n y 
reas o na bl e ste ps t hat ar e re q ueste d b y t he S p o ns or as a res ult of a n a u dit t o c ure deficie n cies i n 
t he st u d y d oc u me nts a n d eC R Fs.  Ot her d oc u m e ntati o n s u bject t o Q A a u dit i ncl u des t he I R B/I E C 
files, certificati o n a n d q u alit y c o ntr ol of s u p p orti n g la b orat ories, a n d rec or ds rele va nt t o t he trial 
i n a n y s u p p orti n g p har mac y facilities. C o n diti o ns of st ora ge of st u d y materials are als o s u bject t o 
i ns pecti o n. S p o ns or re prese ntati ves ma y o bser v e t he c o n d uct of a n y as pect of t he cli nical trial or 
its s u p p orti n g acti vities b ot h wit hi n a n d o utsi de of t he I n v esti gat or's i nstit uti o n. 
1 3  
E T HI C A L A N D L E G A L I S S U E S  
1 3. 1  
Et hic al C o n d uct/ G o o d Cli nic al Pr actice  
T his st u d y will be c o n d u cte d i n acc or da n ce wit h t he et hical pri nci ples t hat ha ve t heir ori gi n i n 
t he c urr e nt Decl arati o n of Helsi n ki a n d will be c o nsiste nt wit h I C H G C P a n d a p plica ble 
re g ulat or y r e q uire me nts.  
1 3. 2  
I nstit uti o n al Re vie w B o ar d/I nde pe n de nt  Et hics C o m mittee  
T his st u d y m ust be re vie we d a n d a p pr o ve d b y t he I R B /I E C re prese nti n g t h e i nstit uti on pri or t o 
e nr olli n g patie nts. T h e I R B /I E C m ust be a p pr o priatel y c o nstit ute d a n d meet all re q uire me nts as 
descri be d i n Part 5 6, Titl e 2 1 of t he C F R  a n d l ocal la ws a n d re g ulati o ns, as a p plica ble. T he 
re vie w m ust i ncl u de b ot h t he pr ot oc ol a n d t he I C F f or t he trial. A c o p y of t he Letter or N otice of 
A p pr o val fr o m t he I R B /I E C m ust be recei ve d b y t he S p o ns or pri or t o s hi p me nt of dr u g s u p plies 
t o t he I n v esti gat or. T he I R B /I E C me m bers hi p list m ust be s u b mitte d t o t he S p o ns or wit h t he 
writte n I R B /I E C a p pr o val a n d up date d lists, if a p plica ble.  
T he I n vesti gat or m ust pr o m ptl y re p ort all c ha n ges i n t he researc h acti vit y a n d all u na ntici pate d 
pr o ble ms i n v ol vi n g ris k t o t he s u bjects or ot hers t o t heir I R B/I E C. T he I n v esti gat or will pr o vi de 
pr o gress r e p orts as r e q uir e d b y t h e I R B/I E C. T h e I n vesti gat or is res p o nsi ble f or ass uri n g 
c o nti n ui n g re vi e w a n d a p pr o val of t he cli nical st u d y o n a n a n n ual basis a n d s u b mitti n g 
d oc u me ntati o n of re n e wal t o t he S p o ns or. T he I n v esti gat or will gi ve n otice t o t he I R B /I E C w he n 
partici pati o n i n  t he st u d y has bee n c o m plet e d. 
1 3. 3  
Writte n I nf or me d C o nse nt  
T he I n vesti gat or a grees t o pr otect t he ri g hts, safet y, a n d welfare of t h e s u bject s e ntere d i nt o t he 
st u d y, i ncl u di n g o bt ai ni n g writte n i nf or me d c o ns e nt pri or t o perf or mi n g a n y st u d y-relate d 
pr oce d ur es a n d i nf or mi n g eac h s u bject t hat t he st u d y dr u g is bei n g us e d f or i n vesti gati o nal 
p ur p oses. A c o p y of t h e I R B -a p pr o v e d I C F t o b e use d d uri n g t h e st u d y m ust be s u b mitte d f or 
S p o ns or re vie w pri or t o st u d y i nitiati o n. 
Pri or t o e ntr y i nt o t he st u d y, t he p ur p ose a n d n at ure of t he st u d y a n d p ossi ble a d vers e effects 
m ust be e x plai ne d t o eac h patie nt. All q uesti o ns a b o ut t he st u d y s h o ul d be a ns were d t o t he 
patie nt’s satisfacti o n or t he patie nt’s le gal re pres e ntati ve. It is t he res p o nsi bilit y of t h e 
I n v esti gat or or desi g nee t o o btai n writte n i nf or me d c o nse nt fr o m eac h pati e nt, t here b y attesti n g 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 5  of 8 0  
 
t hat c o nse nt was freel y gi ve n. A c o p y of t h e si g n e d a n d date d I C F will be gi ve n t o t he patie nt.  
D oc u me ntati o n of t he i nf or me d c o nse nt pr o cess m ust be e vi de nt i n t he patie nt’s cli nical files, 
a n d t he ori gi nal e x ec ute d I C F m ust be a vaila ble f or re vie w b y t h e st u d y m o nit or.  
I n t he e ve nt t hat m o dificati o ns i n t he ex peri me ntal desi g n, d osa ges, tests a n d assess me nts, 
s u bject selecti o n, etc., of t he pr ot oc ol are i n dicate d or re q uire d, a n d i n t he e ve nt t hat s uc h 
m o dificati o ns s u bsta ntiall y alter t h e st u d y d esi g n or i ncrease t he p ote ntial ris k t o s u bjects, 
re visi o ns t o the e xisti n g I C F are als o re q uire d . S uc h a re visi o n will be re vie we d a n d a p pr o ve d b y 
t he a p pr o priat e I R B, a n d d oc u me ntati o n of t his a p pr o val will be f or w ar de d t o t he S p o ns or f or 
s u b missi o n t o t he a p pr o priate re g ul at or y b o d y.  
I n a d diti o n, all c urre nt st u d y partici pa nts, as well as s u bse q ue nt st u d y ca n di dates, will be 
i nf or me d of t he st u d y desi g n m o dificati o n or i ncrease i n p ote ntial ris k, a n d writte n i nf or me d 
c o nse nt will be o btai ne d. 
1 3. 4  
Rec or ds a n d C ase Re p o rt F or ms  
T he I n vesti gat or is r e q uir e d t o pre pare a n d m ai ntai n a de q uate a n d acc urate case hist ories 
desi g ne d t o rec or d all o bser vati o ns a n d ot her d ata perti ne nt t o t he i n vesti gati o n o n eac h 
i n di vi d ual treate d wit h t he st u d y dr u g. Data re p ort e d o n t he e C R F t hat are d eri ve d fr o m s o urce 
d oc u me nts m ust be c o nsiste nt wit h t he s o urce d oc u me nts or t he discre p a ncies m ust be e x plai ne d. 
All re q ueste d i nf or m ati o n m ust be e ntere d o n t he e C R F i n t he fiel ds pr o vi d e d.  
1 3. 5  
Pr ot oc ol D e vi ati o ns 
T he st u d y is t o be c o n d u cte d as des cri be d i n t his pr ot oc ol wit h o ut de viati o n u nless t he re is a 
safet y c o n cer n. T h e pr ot o c ol s h o ul d n ot be m o difie d f or a n y s u bject wit h o ut t he pri or c o nse nt of 
t he S p o ns or a n d, if necessar y, t he I R B /I E C res p o nsi ble at t he i n vesti gati ve site. 
I n t he e ve nt of a vi olati o n, a re p ort will be s u b mitte d t o t he I R B/I E C (as a p plica ble). 
1 3. 6  
Ter mi n ati o n of t he St u d y  
S h o ul d t he S p o ns or a n d/ or t he I n vesti gat or disc o v er c o n diti o ns d uri n g t h e c o urse of t he trial t hat 
i n dicate t hat t he st u d y s h o ul d be disc o nti n ue d, a n a p pr o priate pr oce d ure f or ter mi nati o n will be 
i nstit ute d. 
Reas o ns f or t he cl os ure of a st u d y site or ter mi nati o n of a st u d y b y t h e S p o ns or ma y i n cl u de ( b ut 
are n ot li mite d t o) t he f oll o wi n g:  
•  S uccessf ul c o m pleti o n of t he st u d y at t he st u d y site  
•  T he re q uir e d n u m ber of s u bjects f or t he st u d y has bee n recr uite d 
•  Fail ur e of t he I n vesti gat or  t o c o m pl y wit h t he pr ot oc ol, G C P g ui deli nes or re g ul at or y 
re q uire me nts 
•  Safet y c o ncer ns  
•  I n a de q uat e recr uit me nt of s u bjects b y t he I n vesti gat or 
1 3. 7  
Rete nti o n of Rec or ds  
T he I n vesti gat or/I nstit uti o n s h o ul d mai ntai n t he st u d y d oc u m e nts as s pe cifi e d i n t he I C H 
g ui deli nes o n G C P a n d as re q uire d b y t he a p plica ble re g ulat or y re q uire m e nts. Ca na dia n fe deral 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 6  of 8 0  
 
la w re q uir es all rec or ds create d d uri n g t h e c o n d uct of a cli nical trial f or 2 5 years u n der Di visi o n 
5 of t he Healt h Ca n a da F o o d a n d Dr u g Re g ulati o ns. U S fe deral la w re q uires t hat t he I n v esti gat or 
retai n c o pies of all files p ertai ni n g t o t he trial (i.e. me dical rec or ds, la b orat or y re p orts, dr u g 
i n ve nt or y/ dis p ositi o n rec or ds, si g ne d I C Fs, e C R Fs, all c orres p o n d e nce, d at es a n d re p orts of 
m o nit ori n g visits) f or a p eri o d of 2 years f oll o wi n g t he d ate of mar keti n g a p plicati o n a p pr o val of 
t he dr u g f or t he i n dicati o n i n vesti gate d i n t he st u d y, a n d u ntil t here is n o pe n di n g or 
c o nte m plate d mar k eti n g a p plicati o n, or f or 2 years f oll o wi n g t he S p o ns or’s disc o nti n ui n g 
w orl d wi de cli nical de v el o p me nt of t he st u d y dr u g, as n otifie d b y t h e S p o ns or, w hic he ver is 
l o n ger.  
If t he I n vesti gat or rel ocat es, retires, or wit h dra ws f or a n y reas o n fr o m t he st u d y, trial rec or ds 
ma y b e tra nsf err e d t o a n acce pta ble desi g nee, s uc h as a n ot her I n vesti gat or wit hi n t he i nstit uti o n.  
Pri or n otice of s uc h tra nsfer will be pr o vi de d i n writi n g t o t he S p o ns or. T h e I n vesti gat or m ust 
o btai n writte n per missi o n fr o m t he S p o ns or pri or t o dis p osi n g of a n y rec or ds.  
1 4  
I N V E S TI G A T O R R E S P O N SI BI LI TI E S 
A n I n vesti gat or c o n d u cti n g a cli nical st u d y wit h a n i n vesti gati o nal a ge nt is re q uire d t o c o m pl y 
wit h re g ul ati o ns descri be d i n t he U S C F R , Title 2 1 Part 3 1 2, I C H G C P  g ui deli nes, as well as 
l ocal la ws a n d r e g ulati o ns.  
T he I n vesti gat or: 
•  Will pers o nall y c o n d uct or s u per vise t he c o n d uct of t he st u d y. T h e I n vesti gat or will 
e ns ure t hat all s u b-I n v esti gat ors a n d ot hers assisti n g i n t he trial are a de q uat el y i nf or me d 
a b o ut t he pr ot oc ol, t he st u d y dr u g, a n d t heir trial-relate d d uties a n d f u n cti o ns. 
•  Will ma ke c ha n ges t o t he c o n d uct of t he trial o nl y after recei vi n g t he S p o ns or’s a p pr o v al, 
e x ce pt t o pr otect t he saf et y, ri g hts, or w elfare of s u bject s. 
•  Will n ot discl ose a n y g o o ds, materials, i nf or mati o n ( oral or writte n) a n d u n p u blis he d 
d oc u me ntati o n pr o vi de d b y t he S p o ns or (i n cl u di n g t his pr ot oc ol, t he s u bject e C R Fs, a n d 
t he I B) t o a n y u na ut h orize d pers o n wit h o ut t he S p o ns or’s pri or writte n c o nse nt. 
•  Will mai ntai n a S u bject  Scree ni n g L o g listi n g all s u bjects e ntere d i nt o t he trial, t h ose 
c o nsi dere d f or trial e ntr y a n d s u bse q ue ntl y e x cl u de d, a n d t he reas o n f or e x cl usi o n. 
•  Will st ore st u d y dr u g i n a sec ure l o cati o n, u n der t h e c o n diti o ns i n dicate d i n S e cti o n 8. 9 , 
a n d will mai ntai n a Dr u g I n v e nt or y F or m. Will destr o y use d s u p plies i n a n a p pr o priate 
ma n ner acc or di n g t o i nstit uti o nal p olic y a n d d oc u me nt s uc h destr ucti o n. At t he 
c o m pleti o n of t he trial, t he I n vesti gat or will ret ur n all u n use d trial materials t o t he 
S p o ns or, u nless ot her wise a ut h orize d i n writi n g. 
•  Will rec or d trial data o n eC R Fs f or eac h s u bject w h o recei ves a n y a m o u nt of st u d y dr u g, 
i ncl u di n g t h ose w h o wit h dra w bef ore c o m pleti o n of t he trial. Will e ns ure t he acc urac y, 
c o m plete ness, le gi bilit y,  a n d ti meli ness of t he data re p orte d o n t he e C R F a n d i n re q uire d 
re p orts. Will re vie w eC R Fs f or c o m plete ness a n d acc urac y pri or t o s u b missi o n f or data 
e ntr y. 
•  Will i ncl u de s o urce d oc u me nts s uc h as h os pital, cli nic, or office c harts; la b orat or y 
re p orts; trial w or ks heets; a n d si g ne d I C Fs i n t he I n vesti gat or’s files al o n g wit h s u bject 
trial rec or ds. Will i ncl u de i n t he I C F a stat e me nt all o wi n g t he S p o ns or ( or d esi g nee), as 
well as a ut h orize d re g ulat or y a ge ncies, t o h a ve direct access t o s o urce data t hat s u p p ort 
data re p orte d o n t he e C R F.  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 7  of 8 0  
 
•  Will per mit direct m o nit ori n g a n d a u diti n g b y t he S p o ns or or S p o ns or ’s re prese ntati ves 
a n d i ns pecti o n b y t h e a p pr o priate re g ulat or y a ut h orities. 
•  Will pr o vi de t he S p o ns or wit h t he n or mal la b orat or y ra n ges f or t he la b orat ories t o be 
use d i n t he trial as well as t he la b orat or y certificati o n n u m ber.  Will pr o vi de c o pies of a n y 
a d diti o nal rec or ds p erti ne nt t o t he trial (e . g., ra di ol o g y re p orts, c h art s u m maries, a ut o ps y 
re p orts) t o t he S p o ns or or re g ulat or y a ut h orities, if re q ueste d, wit h d ue preca uti o n ta ke n 
t o e ns ure s u bject c o nfi de ntialit y.  
•  Will mai ntai n s u bject c o nfi de ntialit y at all ti mes d uri n g t he tri al b y usi n g c o de d 
i de ntifiers w he n r eferri n g t o a partic ular s u bject (i ncl u di n g i n a n y p u blicati o ns). 
•  Will i nf or m s u bjects t hat t he st u d y dr u g is bei n g use d f or i n vesti gati o nal p ur p oses 
•  Will re p ort t o t he S p o ns or a n y A Es t hat occ ur d uri n g t he trial i n acc or da nce wit h I C H, 
C F R 2 1 Part 3 1 2. 6 4 a n d l ocal la ws. 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 8  of 8 0  
 
1 5  
R E F E R E N C E S  
C hr o ni c n o n b a ct eri al pr ost atitis ( c hr o ni c p el vi c p ai n s y n dr o m e). H ar v ar d H e alt h P u blis hi n g, 
H ar v ar d M e di c al S c h o ol, H ar v ar d P ers p e cti v es o n Pr ost at e Dis e as e , ac c ess e d 0 7 N o v 2 0 1 7, 
w w w. h e alt h. h ar v ar d. e d u/ n e wsl ett er _ arti cl e/ c hr o ni c -n o n b a ct eri al -pr ost atitis -c hr o ni c -p el vi c -
p ai n . 
Kr o n e n k e K., S pit z er R. L., Willi a ms J. B., T h e P H Q -9: v ali dit y of a bri ef d e pr essi o n s e v erit y 
m e as ur e. J G e n I nt er n M e d, 2 0 0 1. 1 6( 9): p. 6 0 6 -1 3 . 
Lit wi n M S, M c N a u g ht o n -C olli ns M, F o wl er FJ, et al. T h e N ati o n al I nstit ut es of H e alt h 
c hr o ni c pr ost atitis s y m pt o m i n d e x: d e v el o p m e nt a n d v ali d ati o n of a n e w o ut c o m e  m e as ur e. J 
Ur ol. V ol. 1 6 2, 3 6 9 -3 7 5, A u g ust 1 9 9 9.  
Ni c k el, J C. I nfl a m m at or y a n d P ai n C o n diti o ns of t h e M al e G e nit o uri n ar y Tr a ct: Pr ost atitis 
a n d R el at e d P ai n C o n diti o ns, Or c hitis, a n d E pi di d y mitis. I n: C a m p b ell -W als h Ur ol o g y, 
Els e vi er ; 2 0 1 7: 3 0 4 -3 3 3 e 1 3 . 
R o d di c k, J, Hi g u er a V. C hr o ni c N o n b a ct eri al Pr ost atitis. H e alt hli n e , H e alt hli n e M e di a, 2 5 
A u g 2 0 1 7, a c c ess e d 0 7 N o v 2 0 1 7, w w w. h e alt hli n e. c o m/ h e alt h/ pr ost atitis -n o n b a ct eri al -
c hr o ni c . 
R os e n R, Ril e y A, W a g n er G, et al. T h e I nt er n ati o n al I n d e x of Er e ctil e F u n cti o n (II E F): A 
m ulti di m e nsi o n al s c al e f or ass ess m e nt of er e ctil e d ysf u n cti o n. Ur ol o g y, 1 9 9 7, 4 9: 8 2 2 -8 3 0.  
S h os k es D A, a n d Ni c k el J C. Cl assifi c ati o n a n d tr e at m e nt of m e n wit h c hr o ni c 
pr ost atitis/ c hr o ni c p el vi c p ai n s y n dr o m e usi n g t h e U P OI N T s yst e m. W orl d J Ur ol. 2 0 1 3 
A u g; 3 1( 4): 7 5 5 -6 0.  
S ulli v a n M , T h or n B , H a yt h or nt h w ait e J , et al. T h e or eti c al P ers p e cti v es o n t h e R el ati o n 
B et w e e n C at astr o p hi zi n g a n d P ai n . T h e Cli ni c al J o ur n al of P ai n  (2 0 0 1 ) 1 7 : 1 5 2 -6 4.  
S ulli v a n MJ L, Bis h o p S, Pi vi k J. T h e p ai n c at astr o p hi zi n g s c al e: d e v el o p m e nt a n d 
v ali d ati o n. Ps yc h ol Ass ess  (1 9 9 5 ) 7: 5 2 4 -5 3 2.  
St e nt o n G R, M a c k e n zi e L F, T a m P, Cr oss J L, H ar wi g C, R a y m o n d J, T o e ws J, W u J, O g d e n 
N, M a c R ur y T, a n d S z a b o C. C h ar a ct eri z ati o n of A Q X -1 1 2 5, a s m all -m ol e c ul e S HI P 1 
a cti v at or P art 1. Eff e cts o n i nfl a m m at or y c ell a cti v ati o n a n d c h e m ot a xis i n vitr o a n d 
p h ar m a c o ki n eti c c h ar a ct eri z ati o n i n vi v o. BJ P ( 2 0 1 3) 1 6 8 1 5 0 6 – 1 5 1 8.  
St e nt o n G R, M a c k e n zi e L F, T a m P, Cr oss J L, H ar wi g C, R a y m o n d J, T o e ws J, C h er n off D, 
M a c R ur y T, a n d S z a b o  C. C h ar a ct eri z ati o n of A Q X -1 1 2 5, a s m all -m ol e c ul e S HI P 1 
a cti v at or. P art 2. Effi c a c y st u di es i n all er gi c a n d p ul m o n ar y i nfl a m m ati o n m o d els i n vi v o. 
BJ P ( 2 0 1 3) 1 6 8 1 5 1 9 – 1 5 2 9 1 5 1 9 .

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
 
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 5 9  of 8 0  
 
1 6  
A P P E N DI C E S  
A p pe n di x 1. P ai n C at astr o p hizi n g Sc ale 
 
 
 
 

Ψ   
C o p yri g ht  1 9 9 5  
 Mic hael J L S ulli va n   
P C S
 
A g e: _ _ _ _ _  
S e x:  
M( _ _)  
F( _ _)  
 
E v er y o n e e x p eri e n c e s p ai nf ul sit u ati o n s at s o m e p oi nt i n t h eir li v e s. T h e s e e x p eri e n c e s m a y i n cl u d e 
h e a d a c h e s, t o ot h p ai n, j oi nt or m u s cl e p ai n. P e o pl e ar e oft e n e x p o s e d t o sit u ati o n s t h at m a y c a u s e 
p ai n s u c h a s ill n e s s, i nj ur y, d e nt al pr o c e d ur e s or s ur g er y.  
 
W e ar e i nt er e st e d i n t h e t y p e s of t h o u g ht s a n d f e eli n g s t h at y o u h a v e w h e n y o u ar e i n p ai n. T hirt e e n 
st at e m e nt s ar e li st e d b el o w d e s cri bi n g diff er e nt t h o u g ht s a n d f e eli n g s t h at m a y b e a s s o ci at e d wit h 
p ai n. U si n g t h e f oll o wi n g s c al e, pl e a s e i n di c at e t h e d e gr e e t o w hi c h y o u h a v e t h e s e t h o u g ht s a n d 
f e eli n g s w h e n y o u ar e e x p eri e n ci n g p ai n. 
 
0  ‒  n ot at all  1  ‒  t o a sli g ht d e gr e e 2  ‒  t o a m o d er at e d e gr e e 3  ‒  
t o a gr e at d e gr e e 4  ‒  all t h e ti m e  
 
W he n I’ m i n p ai n... 
1  
I w orr y all t he ti me a b o ut w het her t he pai n will e n d. 
2  
I feel I ca n’t g o o n. 
3  
It’s terri ble a n d I t hi n k it’s ne ver g oi n g t o get a n y better. 
4  
It’s a wf ul a n d I feel t hat it o ver w hel ms me. 
5    I feel I ca n’t sta n d it a n y m ore. 
6  
 I bec o me afrai d t hat t he pai n will get w orse. 
7  
I kee p t hi n ki n g of ot her pai nf ul e ve nts. 
8  
I a n xi o usl y wa nt t he pai n t o g o a wa y. 
9  
I ca n’t see m t o kee p it o ut of m y mi n d. 
1 0  
I kee p t hi n ki n g a b o ut h o w m uc h it h urts. 
1 1  
I kee p t hi n ki n g a b o ut h o w ba dl y I wa nt t he pai n t o st o p. 
1 2  
T here’s n ot hi n g I ca n d o t o re d uce t he i nte nsit y of t he pai n. 
1 3  
I w o n der w het her s o met hi n g seri o us ma y ha p pe n. 
 
 
 
... T ot al 
 
P C S - Unit e d S t at e s/ E n gli s h - V er si o n of 2 4 A pril  1 7 - M a pi.  
I D 0 5 8 1 2 7 / P C S _ AU 1. 0 _ e n g -U S . d o c 

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 6 1  of 8 0  
A p pe n di x 2. P a tie nt He alt h Q uesti o n n aire  9-Ite ms 

P A TI E N T H E A L T H Q U E S TI O N N AI R E ( P H Q- 9)
D A T E:
N A M E:
O v er t h e l a st 2 w e e k s, h o w oft e n h a v e y o u b e e n
b ot h er e d b y a n y of t h e f oll o wi n g pr o bl e m s ?
N ot at all
S e v er al
d a y s
M or e t h a n
h alf t h e
d a y s
N e arl y
e v er y d a y
( u s e "ⁿ " t o i n di c at e y o ur a n s w er)
0
1
2
3
Littl e i nt er e st or pl e a s ur e i n d oi n g t hi n g s
1.
0
1
2
3
F e eli n g d o w n, d e pr e s s e d, or h o p el e s s
2.
0
1
2
3
Tr o u bl e f alli n g or st a yi n g a sl e e p, or sl e e pi n g t o o m u c h
3.
0
1
2
3
F e eli n g tir e d or h a vi n g littl e e n er g y
4.
0
1
2
3
P o or a p p etit e or o v er e ati n g
5.
0
1
2
3
F e eli n g b a d a b o ut y o ur s elf   or t h at y o u ar e a f ail ur e or
h a v e l et y o ur s elf or y o ur f a mil y d o w n
6.
0
1
2
3
Tr o u bl e c o n c e ntr ati n g o n t hi n g s, s u c h a s r e a di n g t h e
n e w s p a p er or w at c hi n g t el e vi si o n
7.
0
1
2
3
M o vi n g or s p e a ki n g s o sl o wl y t h at ot h er p e o pl e c o ul d
h a v e n oti c e d. Or t h e o p p o sit e    b ei n g s o fi g et y or
r e stl e s s t h at y o u h a v e b e e n m o vi n g ar o u n d a l ot m or e
t h a n u s u al
8.
0
1
2
3
T h o u g ht s t h at y o u w o ul d b e b ett er off d e a d, or of
h urti n g y o ur s elf
9.
a d d c ol u m n s
+
+
T O T A L:
( H e alt h c ar e pr of e s si o n al: F or i nt er pr et ati o n of T O T A L,
pl e a s e r ef er t o a c c o m p a n yi n g s c ori n g c ar d).
N ot diffi c ult at all
If y o u c h e c k e d off a n y pr o bl e m s, h o w diffi c ult
h a v e t h e s e pr o bl e m s m a d e it f or y o u t o d o
y o ur w or k, t a k e c ar e of t hi n g s at h o m e, or g et
al o n g wit h ot h er p e o pl e ?
1 0.
S o m e w h at diffi c ult
V er y diffi c ult
E xtr e m el y diffi c ult
C o p yri g ht 
 1 9 9 9 Pfi z er I nc. All ri g hts res er v e d. Re pr o d uc e d wit h per missi o n. P RI M E- M D
 is a tr a de m ar k of Pfi zer I nc.
A 2 6 6 3 B 1 0- 0 4- 2 0 0 5
 
  
 
 
P A TI E N T H E A L T H Q U E S TI O N N AI R E ( P H Q- 9)
A q ui n o x A Q X- 1 1 2 5- 2 0 5 
S u bject Scree n N u m ber/ Ra n d o mizati o n N u m ber _ _ _ _ _ _ _ _ _ _ _ _ _  
Visit Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ Visit N u m ber _ _ _ _ _ _ _ _ _ _ _ _ 

P H Q- 9 Patie nt De pressi o n Q uesti o n naire 
F or i niti al di a g n osis: 
1. 
Patie nt c o m pletes P H Q- 9 Q u ic k De pressi o n Assess me nt.
2.
If t here are at least 4 
s i n t he s ha de d secti o n (i ncl u di n g Q uesti o ns # 1 a n d # 2), c o nsi der a de pressi ve
dis or der. A d d sc ore t o deter mi ne se verit y.
C o nsi der M aj or De pressive Dis or der 
 
- if t here are at least 5 
s i n t he s ha de d secti o n ( o ne of w hic h c orres p o n ds t o Q uesti o n # 1 or # 2)
C o nsi der Ot h er De pressive Dis or der 
 
- if t here are 2- 4 
s i n t he s ha de d secti o n ( o ne of w hic h c orres p o n ds t o Q uesti o n # 1 or # 2)
N o te: Si nce t he questi o n naire relies o n patie nt self-re p ort, all res p o nses s h o ul d be verifie d b y t he cli nicia n, 
a n d a defi niti ve dia g n osis is ma de o n cli nical gr o u n ds ta ki n g i nt o acc o u nt h o w we ll t he patie nt u n derst o o d 
t he q uesti o n naire, as well as ot her releva nt i nf or mati o n fr o m t he patie nt.  
Dia g n oses of Maj or De pressi ve Dis or der or Ot her De pressi ve Dis or der als o re q uire i m p air me nt of s ocial, 
occ u pati o nal , or ot her i m p orta nt areas of f u ncti o ni n g ( Q uesti o n # 1 0) a n d r uli n g o ut n or mal berea ve me nt, a 
hist or y of a Ma nic E pis o de ( Bi p olar Dis or der), a n d a p h ysical dis or der, me dicati o n, or ot her dr u g as t he 
bi ol o gical ca use of t he de pressi ve s y m pt o ms.  
T o m o nit or se verit y o ver ti me f or ne wl y di a g n ose d p atie nts or p atie nts i n c urre nt tre at me nt f or 
de pressi o n: 
1. 
Patie nts ma y c o m plete q uesti o n naires at baseli ne a n d at re g ular i nter vals (e g, e ver y 2 wee ks) at
h o me a n d bri n g t he m i n at t heir ne xt a p p oi nt me nt f or sc ori n g or t he y ma y c o m plete t he
q uesti o n naire d uri n g eac h sc he d ule d a p p oi nt me nt.
2.  
A d d u p 
s b y c ol u m n. F or e ver y 
: Se veral da ys = 1 M ore t ha n half t he da ys = 2 Nearl y e ver y da y = 3
3.  
A d d t o get her c ol u m n sc ores t o get a T O T A L sc ore.
4. 
Refer t o t he acc o m pa n yi n g  P H Q- 9 Sc ori n g B o x t o i nter pret t he T O T A L sc ore.
5.
Res ults ma y be i ncl u de d i n patie nt files t o assist y o u i n setti n g u p a treat me nt g oal, deter mi ni n g de gree of
res p o nse, as well as g ui di n g treat me nt i nter ve nti o n.
Sc ori n g:  a d d u p all c hec ke d b o xes o n P H Q- 9 
F or e ver y   N ot at all = 0; Se veral da ys = 1; 
M ore t ha n half t he da ys = 2; Nearl y e ver y da y = 3 
I nter pret ati o n of T ot al Sc ore  
T ot al Sc ore 
De pressi o n Se verit y 
1- 4
 Mi ni mal de pressi o n 
5- 9
 Mil d de pressi o n 
1 0- 1 4
 M o derate de pressi o n
1 5- 1 9
 M o deratel y se vere de pressi o n 
2 0- 2 7
 Se vere de pressi o n
P H Q 9 C o p yri g ht © Pfizer I nc.  All ri g hts reser ve d .  Re pr o d uce d wit h per missi o n. P RI M E- M D ® is a 
tra de mar k of Pfizer I nc. 
A 2 6 6 2 B 1 0- 0 4- 2 0 0 5 
Versi o n 3 . 0/ A me n d me nt 2
A q ui n o x A Q X- 1 1 2 5- 2 0 5 
S u bject Scree n N u m ber/ Ra n d o mizati o n N u m ber _ _ _ _ _ _ _ _ _ _ _ _ _  
Visit Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ Visit N u m ber _ _ _ _ _ _ _ _ _ _ _ _ 
C O N FI D E N TI A L
Pa ge 6 3  of 80

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 6 4  of 8 0  
A p pe n di x 3. 1 1- p oi nt N u meric al R ati n g Sc ale 

1 1- P oi nt N u meric al R ati n g Sc ale f or P ai n * ( Cli nic)
P E L VI C  P AI N C LI NI C A S S E S S M E N T  
Ple as e assess y o ur a ver a ge a n d w orst pel vic  p ai n f or e ac h d a y o n a sc ale of 0- 1 0: 
W h at n u m ber w o ul d y o u gi ve y o ur a ver a ge pel vic p ai n o ver t he l ast 2 4 h o urs ? 
N o  
    Pel vic   
Pel vic   0  
 1  
 2  
 3  
 4  
 5  
 6  
 7  
 8  
 9 
1 0     Pai n as ba d  
Pai n
as y o u ca n 
i ma gi ne 
W h at n u m ber w o ul d y o u gi ve y o ur w orst pel vic p ai n o ver t he l ast 2 4 h o urs ? 
N o  
     Pel vic  
Pel vic   0  
 1  
 2  
 3  
 4  
 5  
 6  
 7  
 8  
 9  
1 0      Pai n as  ba d    
Pai n  
           as y o u ca n   
          i ma gi ne 
*A da pte d fr o m Mc Caffer y, M. Bee be A, et al. ( 1 9 8 9). Pai n: Cli nical ma n ual f or n ursi n g practice,
M os b y St. L o uis, M
      0  
  1  
  2  
  3  
  4  
  5  
  6  
  7  
  8  
  9  
   1 0  
N o P el vic P ai n  
P el vic P ai n as 
b a d a s y o u 
c a n im a gi ne
Versi o n 3 . 0/ A me n d me nt 2
 
C O N FI D E N TI A L
Pa ge 6 5  of 8 0

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 6 6  of 8 0  
A p pe n di x 4. N ati o n al I nstit utes of He alt h  C hr o nic Pr ost atitis S y m pt o m I n de x 

A q ui n o x A Q X- 1 1 2 5- 2 0 5  
S u bj e ct S cr e e n N u m b er/ R a n d o mi z ati o n N u m b er _ _ _ _ _ _ _ _ _ _ _ _ _  
Vi sit D at e _ _ _ _ _ _ _ _ _ _ _ _ _ _ Vi sit N u m b er _ _ _ _ _ _ _ _ _ _ _ _  
NI H- C hr o ni c Pr o st atiti s S y m pt o m I n d e x ( NI H- C P SI) 
P ai n or Di s c o mf ort 
1. I n t h e l a st w e e k, h a v e y o u e x p eri e n c e d a n y p ai n or di s c o mf ort 
i n t h e f oll o wi n g ar e a s ? 
 Y e s      
   N o 
a. 
Ar e a b et w e e n r e ct u m a n d  
    ❑1        
     ❑0 
t e sti cl e s ( p eri n e u m) 
b.  T e sti cl e s
   ❑1         
    ❑0 
c.  Ti p of t h e p e nis ( n ot r el at e d t o      ❑1  
    ❑0 
uri n ati o n) 
d.  B el o w y o ur w ai st, i n y o ur 
    ❑1        
     ❑0 
p u bi c or bl a d d er ar e a 
2.  I n t h e l a st w e e k, h a v e y o u e x p eri e n c e d: 
  Y e s     
    N o 
a. 
P ai n or b ur ni n g d uri n g
      ❑1       
  ❑0 
uri n ati o n ? 
b. 
P ai n or disc o mf ort d uri n g or
 ❑1       
    ❑0 
aft er s e x u al cli m ax ( ej ac ul ati o n) ? 
3.  H o w oft e n h a v e y o u h a d p ai n or di s c o mf ort i n a n y of 
t h e s e ar e a s o v er t h e l a st w e e k ? 
❑ 0 N e v er 
❑ 1 R ar el y
❑ 2 S o m eti m es 
❑ 3 Oft e n 
❑ 4 U s u all y 
❑ 5 Al w ays 
4.  
W hi c h n u m b er b e st d e s cri b e s y o ur A V E R A G E p ai n or
di s c o mf ort o n t h e d a y s t h at y o u h a d it, o v er t h e l a st w e e k ? 
❑ 
❑   ❑  ❑    ❑ 
❑    ❑ 
❑    ❑ 
❑   ❑
0      1      2     3        4      5       6     7      8     9     1 0 
N O        
 P AI N A S 
P AI N
B A D A S 
  Y O U C A N 
 I M A GI N E 
Uri n ati o n 
5.  
H o w oft e n h a v e y o u h a d a s e n s ati o n of n ot e m pt yi n g y o ur bl a d d er 
c o m pl et el y aft er y o u fi ni s h e d uri n ati n g, o v er t h e l a st w e e k ? 
❑0  N ot at all 
❑1  L e s s t h a n 1 ti m e i n 5
❑2 L e s s t h a n h alf t h e ti m e 
❑3  A b o ut h alf t h e ti m e 
❑4 M or e t h a n h alf t h e ti m e 
❑5  Al m ost al w ays 
6.  H o w oft e n h a v e y o u h a d t o uri n at e a g ai n l e s s t h a n t w o 
h o ur s aft er y o u fi ni s h e d uri n ati n g, o v er t h e l a st w e e k ? 
❑0   N ot at all
❑1  L e s s t h a n 1 ti m e i n 5
 ❑2   L e s s t h a n h alf t h e ti m e 
❑3  A b o ut h alf t h e ti m e
❑4  M or e t h a n h alf t h e ti m e
❑5   Al m ost al w ays 
I m p a ct of S y m pt o m s
7.  H o w m u c h h a v e y o ur s y m pt o m s k e pt y o u fr o m d oi n g 
t h e ki n d s of t hi n g s y o u wo ul d u s u all y d o, o v er t h e 
l a st w e e k ? 
❑0  N o n e
❑1  O nl y a littl e  
 ❑2   S o m e
❑3  A l ot 
8.  H o w m u c h di d y o u t hi n k a b o ut y o ur s y m pt o m s, o v er t h e 
l a st w e e k ? 
❑0  N o n e
❑1  O nl y a littl e  
 ❑2   S o m e
❑3  A l ot 
Q u alit y of Lif e
9.  If y o u w er e t o s p e n d t h e r e st of y o ur lif e wit h y o ur 
s y m pt o m s j u st t h e w a y t h e y h a v e b e e n d uri n g t h e l a st 
w e e k, h o w w o ul d y o u f e el a b o ut t h at ? 
❑0   D eli g ht e d
❑1  Pl e a s e d  
 ❑2   M o stl y s ati sfi e d
❑3  Mi x e d ( a b o ut e q u all y s atisfi e d a n d dis s ati sfi e d)
 ❑4   M ostly diss atisfi e d 
❑5   U n h a p p y 
❑6   T erri bl e 
Sc ori n g t he NI H- C hr o nic Pr os tatitis S y m pt o m I n de x D o mai ns 
P ai n : T otal of ite ms 1a, 1 b, 1c, 1 d, 2a, 2 b, 3, a n d         = _ _ _ _ _ 
Uri n ary Sy m pt o ms : T otal of ite ms 5 a n d 6    
 = _ _ _ _ _ 
Q u ality of Life I m p act : T otal of ite ms 7, 8, a n d 9       = _ _ _ _ _ 
Versi o n 3 . 0/ A me n d me nt 2
C O N FI D E N TI A L
Pa ge 6 7  of 80

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 6 8  of 8 0  
A p pe n di x 5. I nter n ati o n al I n de x of Erectile F u ncti o n Q uesti o n n aire  

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 7 5  of 8 0  
A p pe n di x  6. Gl o b al Res p o nse Assess me nt  

A q ui n o x A Q X- 1 1 2 5- 2 0 5  
S u bject Scree n N u m ber/ Ra n d o mizati o n N u m ber _ _ _ _ _ _ _ _ _ _ _ _ _   
Visit Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ Visit N u m ber _ _ _ _ _ _ _ _ _ _ _ _  
Gl o b al Res p o nse Assess me nt ( G R A) 
“ As c o m pare d t o w he n y o u starte d t he st u d y dr u g, h o w w o ul d y o u rate y o ur C hr o nic 
Pr ostatitis/ C hr o nic Pel vic Pai n S y n dr o me s y m pt o ms n o w? ”  
- 3:
  M A R K E D L Y W O R S E 
- 2:
  M O D E R A T E L Y W O R S E 
- 1:
  S LI G H T L Y W O R S E 
0: 
  N O C H A N G E 
+ 1:
  S LI G H L T Y I M P R O V E D 
+ 2:
  M O D E R A T E L Y I M P R O V E D 
+ 3:
Versi o n 3 . 0/ A me n d me nt 2
  M A R K E D L Y I M P R O V E D 
Nic kel J C, At ki ns o n G, Krie ger J N et al.: Pr eli mi nar y Assess me nt of Safet y a n d Efficac y 
i n Pr o of- of- C o nce pt, Ra n d o mize d Cli nical Trial of Ta nez u ma b f or C hr o nic 
Pr ostatitis/ C hr o nic Pel vic Pai n S y n dr o me. Ur ol o g y. 2 0 1 2 N o v; 8 0( 5): 1 1 0 5- 1 0. 
C O N FI D E N TI A L
Pa ge 7 6  of 8 0

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 7 7  of 8 0  
A p pe n di x  7. P atie nt’s Gl o b al I m pressi o n of C h a n ge Sc ale 

A q ui n o x A Q X -1 1 2 5 -2 0 5  
S u bj ect Scree n N u m ber/ Ra n d o mizati o n N u m ber _ _ _ _ _ _ _ _ _ _ _ _ _  
Visit Date _ _ _ _ _ _ _ _ _ _ _ _ _ _  Visit N u m ber _ _ _ _ _ _ _ _ _ _ _ _  
P GI -C Q u e sti o n n air e  
P GI -C Q u e sti o n n air e C o m pl et e d ?  
_ _   
D at e P GI -C  Q u e sti o n n air e C o m pl et e d 
m o nt h _ _ _ _     d a y _ _ _ _     y e ar _ _ _ _ _ _ _ _   
Pl e a s e c h o o s e t h e r e s p o n s e b el o w t h at b e st d e s cri b e s t h e o v er a ll c h a n g e i n y o ur p el vi c p ai n si n c e y o u 
st art e d t h e st u d y  
1. V er y m u c h i m pr o v e d
2.  M u c h i m pr o v e d
3.  Mi ni m all y i m pr o v e d
4.  N o c h a n g e
5.  Mi ni m all y w or s e
6.  M u c h w or s e
Versi o n 3 . 0/ A me n d me nt 2
7. V er y m u c h w or s e
C O N FI D E N TI A L
Pa ge 7 8 of 8 0

A q ui n o x P har mace uticals ( Ca na da)  I nc. 
Pr ot oc ol A Q X -1 1 2 5 -2 0 5  
V ersi o n 3. 0/ A me n d me nt 2  
C O N FI D E N TI A L  
P a ge 7 9  of 8 0  
A p pe n di x  8. P atie nt’s Gl o b al I m pressi o n of Se verit y Sc ale  

A q ui n o x A Q X -1 1 2 5 -2 0 5  
S u bj ect Scree n N u m ber/ Ra n d o mizati o n N u m ber _ _ _ _ _ _ _ _ _ _ _ _ _  
Visit Date _ _ _ _ _ _ _ _ _ _ _ _ _ _  Visit N u m ber _ _ _ _ _ _ _ _ _ _ _ _  
P GI -S Q u e sti o n n air e  
P GI -S Q u e sti o n n air e C o m pl et e d ?  
_ _   
D at e P GI -S  Q u e sti o n n air e C o m pl et e d 
m o nt h _ _ _ _     d a y _ _ _ _     y e ar _ _ _ _ _ _ _ _   
Pl e a s e c h o o s e t h e r e s p o n s e t h at b e st d e s cri b e d t h e s e v erit y of y o ur c hr o ni c pr o st atiti s, c hr o ni c p el vi c 
p ai n s y m pt o m s o v er t h e p a st w e e k  
1.  N o n e
2.  Mil d
3.  M o d er at e
4. S e v er e
Versi o n 3 . 0/ A me n d me nt 2
5. V er y S e v er e
C O N FI D E N TI A L
Pa ge 8 0  of 80