Bioequivalence Study of Two Treatments in the Treatment of Inflammatory Lesions of Rosacea on the Face
Phase: PHASE3
Conditions: Rosacea
Sponsor: Padagis LLC

 
 
NCT02800148 
 
10-04-2016 

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P a g e 3 of 5 3  
 
T A BL E O F C O N T E N T S  
 
 
T A BL E O F C O N T E N T S  ........................................................................................................................... 3 
A B B R E VI A TI O N S  .................................................................................................................................. 8 
1.  B A C K G R O U N D  ............................................................................................................................... 9 
2.  S T U D Y O BJ E C TI V E S  ........................................................................................................................ 9 
3. S T U D Y D E SI G N  ................................................................................................................................ 1 0  
3. 1 T y p e/ D esi g n of St u dy  .................................................................................................................. 1 0  
3. 2 St u dy P o p ul ati o n  ......................................................................................................................... 1 0  
4. S EL E C TI O N A N D WI T H D R A W AL O F S T U D Y S U B J E C T S ........................................................................ 1 0  
4. 1 I ncl usi o n Crit eri a  ......................................................................................................................... 1 0  
4. 2 Ex cl usi o n Crit eri a ......................................................................................................................... 1 1  
4. 3 Pr o hi bit e d M e dic ati o ns  ............................................................................................................... 1 4  
4. 4 Pr ec a uti o ns  ................................................................................................................................. 1 5  
5.  P R O C E D U R E S  ................................................................................................................................ 1 6  
5. 1 S u bj ect Scr e e ni n g a n d E nr oll m e nt  .............................................................................................. 1 6  
5. 2 Assi g n m e nt of S u bj ect N u m b er  .................................................................................................. 1 6  
5. 3 D e m o gr a p hics/ M e dic al Hist ory  .................................................................................................. 1 7  
5. 4 C o nc o mit a nt M e dic ati o ns  ........................................................................................................... 1 7  
5. 5 P hysic al Ex a mi n ati o n  ................................................................................................................... 1 7  
5. 6 Uri n e Pr e g n a nc y T est  .................................................................................................................. 1 7  
5. 7 D er m at ol o gic al Ass ess m e nt ( Di a g n osis)  ..................................................................................... 1 8  
5. 8 I nv esti g at or’s Gl o b al Ass ess m e nt (I G A)  ...................................................................................... 1 8  
5. 9 Ev al u ati o n of Tr e at m e nt Ar e a  ..................................................................................................... 1 8  
5. 9. 1 I nfl a m m at ory L esi o n C o u nt ( P a p ul es a n d P ust ul es)  ........................................................... 1 9  
5. 9. 2 Er yt h e m a S ev erit y Ass ess m e nt  .......................................................................................... 1 9  
5. 9. 3 T el a n gi ect asi a E v al u ati o n  ................................................................................................... 1 9  
5. 1 0 A p plic ati o n Sit e R e acti o n Ass ess m e nt  ...................................................................................... 1 9  
5. 1 1 St u dy M e dic ati o n Us e, S u bj ect I nstr ucti o ns a n d Di ar y  ............................................................. 2 1  
5. 1 2 Visit S p ecific Pr oc e d ur es  ........................................................................................................... 2 2  
5. 1 2. 1 B a s eli n e Visit 1/ D ay 1 ...................................................................................................... 2 2  
5. 1 2. 2 T el e p h o n e C o nt act/ W e ek 2/ D a y 1 4 ( ± 4 d ays)  ................................................................ 2 3  
5. 1 2. 3 Visit 2/ W e e k 4/ D a y 2 8 ( ± 4 d a ys)  ..................................................................................... 2 3  
5. 1 2. 4 Visit 3/ W e e k 8/ D a y 5 6 ( ± 4 d a ys)  ........................................................................................... 2 4  
5. 1 2. 5 Visit 4/ W e e k 1 2/ D ay 8 4 ( ± 4 d ays) E n d of Tr e at m e nt/ E arly T er mi n ati o n Visit  ..................... 2 4  
5. 1 2. 6 U nsc h e d ul e d Visit  .................................................................................................................. 2 4  
5. 1 3 S u m m ary of Ass ess m e nts ......................................................................................................... 2 5  
5. 1 4 Scr e e n F ail ur es  .......................................................................................................................... 2 7  
5. 1 5 Pr ot oc ol D evi ati o ns/ Vi ol ati o ns  ................................................................................................. 2 7  
5. 1 6 S u bj ect/ Tr e at m e nt C o m pli a nc e  ................................................................................................ 2 7  
5. 1 7 Disc o nti n u ati o n/ Wit h dr a w al of St u dy S u bj ects  ........................................................................ 2 8  
6. M A T E RI AL S A N D S U P PLI E S  ................................................................................................. 2 9  

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6. 1 St u dy M e dic ati o n  ........................................................................................................................ 2 9  
6. 2 M e dic ati o n M a n a g e m e nt  ........................................................................................................... 2 9  
6. 2. 1 L a b eli n g, P ac k a gi n g a n d Distri b uti o n  ...................................................................................... 2 9  
6. 2. 2 R et e nti o n S a m pl es  ................................................................................................................... 3 0  
6. 2. 3 St or a g e a n d T est Articl e Acc o u nt a bility  ................................................................................... 3 0  
6. 2. 4 R a n d o miz ati o n  ......................................................................................................................... 3 1  
6. 2. 5 Pr oc e d ur e f or Br e a ki n g t h e Bli n d  ............................................................................................. 3 1  
7.  A D V E R S E R E A C TI O N S ........................................................................................................ 3 1  
7. 1 D e p art ur e fr o m t h e Pr ot oc ol f or I n di vi d u al S u bj ects  ................................................................. 3 2  
7. 2 D efi niti o ns  ................................................................................................................................... 3 2  
7. 3 Eliciti n g a n d R e p orti n g of A dv ers e E v e nts  .................................................................................. 3 3  
7. 3. 1 Ex p e dit e d R e p orti n g R es p o nsi biliti es of t h e St u dy C e nt er  ...................................................... 3 4  
7. 3. 2 S u b mitti n g a n Ex p e dit e d S af ety R e p ort t o t h e I R B  .................................................................. 3 4  
7. 4 S A E & A Es R e q uiri n g Disc o nti n u ati o n of St u dy Dr u g, i ncl u di n g Pr e g n a nci es  ............................. 3 5  
7. 4. 1 Pr e g n a nc y  ................................................................................................................................. 3 6  
7. 5 P ost St u dy A dv ers e E v e nts  .......................................................................................................... 3 7  
7. 5. 1 N o n -s eri o us A dv ers e E v e nts .................................................................................................... 3 7  
7. 5. 2 S eri o us A dv ers e E v e nts  ............................................................................................................ 3 7  
8. S T A TI S TI C AL A N AL Y SI S  ....................................................................................................... 3 7  
8. 1 St atistic al A n al ysis Pl a n  ............................................................................................................... 3 7  
8. 1. 1 A nal ysis P o p ulati o ns .................................................................................................... 3 7  
8. 1. 2 Pl a n n e d A n alysis  ...................................................................................................................... 3 8  
8. 1. 3 S a m pl e Siz e C o nsi d er ati o ns  ..................................................................................................... 3 9  
8. 1. 4 Efficac y Meas ures a n d A nal ysis .................................................................................. 3 9  
8. 1. 5 Safet y a n d A d verse E ve nts A nal ysis ............................................................................ 4 0  
8. 2 C o m p ar a bilit y of S u bj ects at B as eli n e  ......................................................................................... 4 0  
9. C O N S E N T C O N SI D E R A TI O N S A N D P R O C E D U R E S  ................................................................. 4 0  
9. 1 S u bj ect C o nfi d e nti ality  ................................................................................................................ 4 1  
1 0. 1 C o m pl eti o n of St u dy  ................................................................................................................. 4 2  
1 0. 2 Pr ot oc ol A m e n d m e nts  .............................................................................................................. 4 2  
1 1. R E C O R D S M A N A G E M E N T  ................................................................................................. 4 2  
1 1. 1 D at a C oll ecti o n  .......................................................................................................................... 4 2  
1 1. 2 S o urc e D oc u m e nts  .................................................................................................................... 4 3  
1 1. 3 Fil e M a n a g e m e nt at t h e St u dy Sit e  ........................................................................................... 4 4  
1 1. 4 R ec or ds R et e nti o n at t h e St u dy Sit e  ......................................................................................... 4 4  
1 2. Q U ALI T Y C O N T R OL A N D Q U ALI T Y A S S U R A N C E ................................................................. 4 4  
1 2. 1 M o nit ori n g  ................................................................................................................................ 4 4  
1 2. 2 A u diti n g  ….................................................................................................. ….. … … …. … … … … ….. … 4 4  
1 3. E T HI C S A N D R E S P O N SI BILI T Y  ............................................................................................ 4 4  
1 4. U S E O F I N F O R M A TI O N A N D P U BLI C A TI O N  ........................................................................ 4 5  
I N V E S TI G A T O R A G R E E M EN T  .................................................................................................. 4 6  
1 5. A P P E N DI C E S  ..................................................................................................................... 4 7  
1 5. 1 A p p e n dix A: St u dy P ers o n n el C o nt acts  ..................................................................................... 4 7  

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1 5. 2 A P P E N DI X B:  I N S T R U C TI O N S F O R T H E S U BJ E C T  .............................................................. 4 8  
1 5. 3 A P P E N DI X C:  F A C E DI A G R A M  ......................................................................................... 5 2  
1 6. R E F E R E N C E S  ..................................................................................................................... 5 3  

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S T U D Y S Y N O P SI S  
 
Titl e:  
A  M ulti -C e nt er,  D o u bl e -Bli n d,  R a n d o miz e d,  V e hicl e -C o ntr oll e d,  P ar all el -
Gr o u p St u d y t o C o m p ar e P erri g o U K FI N C O’s Az el aic Aci d F o a m, 1 5 % t o B a y er 
H e alt h C ar e P h ar m ac e utic als I nc., Fi n ac e a ® (Az el aic aci d) F o a m, 1 5 %, a n d B ot h 
Acti v e Tr e at m e nts t o a V e hicl e C o n tr ol i n t h e Tr e at m e nt of I nfl a m m at or y 
L esi o ns of R os ac e a  
St u d y P eri o d:  
1 2 w e e ks ( 8 4 D a ys)  
St u d y M e dic ati o n:  
1.  Az el aic Aci d F o a m, 1 5 %, o w n e d b y P erri g o U K FI N C O, m a n uf act ur e d b y  
P erri g o Isr a el P h ar m ac e utic als Lt d.  
 
2.  Fi n ac e a ® ( Az el aic A ci d F o a m ,  1 5 %) m a n uf act ur e d  b y  B a y er  H e alt h C ar e  
P h ar m ac e utic als I nc.  
3.  V e hicl e of t est pr o d uct, m a n uf act ur e d b y  P erri g o Isr a el P h ar m ac e utic als 
Lt d. 
St u d y O bj ecti v es:  
T o c o m p ar e t h e s af et y a n d effic acy pr ofil es of P erri g o U K FI N C O’s Az el aic Aci d 
F o a m, 1 5 %, t o B a y er H e alt h C ar e P h ar m ac e utic als I nc., Fi n ac e a ® ( Az el aic Aci d) 
F o a m,  1 5 %,  i n  or d er  t o  pr o v e  bi o e q ui v al e nc e  b et w e e n  t h e m  a n d  t o  
d e m o nstr at e t h e s u p eri or effic acy of t h e t w o activ e f or m ul ati o ns o v er t h at of 
t h e v e hicl e i n t h e tr e at m e nt of I nfl a m m at or y L esi o ns of R os ac e a. 
St u d y D esi g n:  
S u bj ects i n t his m ulti -c e nt er, d o u bl e-bli n d, r a n d o miz e d, v e hicl e -c o ntr oll e d, 
p ar all el -gr o u p  st u d y  will  b e  a d mitt e d  i nt o  t h e  st u d y  o nl y  aft er  writt e n  
i nf or m e d c o ns e nt h as b e e n o bt ai n e d a n d aft er all i ncl usi o n/ excl usi o n crit eri a 
h a v e b e e n m et.  M al e a n d f e m al e s u bj ects at l e ast 1 8 y e ars of a g e wit h 
m o d er at e  p a p ul o p ust ul ar 
r os ac e a  I G A  gr a d e  3 wit h  1 2  t o  5 0  f aci al  
i nfl a m m at or y l esi o ns ( p a p ul es a n d p ust ul es), at l e ast m o d er at e p ersist e nt  
er yt h e m a a n d pr es e nc e of t el a n gi ect asi a  will b e eli gi bl e f or e nr oll m e nt.  
St u d y P o p ul ati o n:  
A p pr oxi m at el y  
 h e alt h y m al es a n d f e m al es, at l e ast 1 8 y e ars of a g e, w h o 
m e et t h e i ncl usi o n/ excl usi o n cr it eri a, will b e e nr oll e d t o o bt ai n a p pr oxi m at el y 
 m o difi e d-I nt e nt-T o -Tr e at ( mI T T) a n d  
 p er -pr ot oc ol ( P P) s u bj ects.  
D osi n g:  
S u bj ects  will  b e  r a n d o miz e d  i n  a   
 t o  eit h er  t h e  t est  pr o d uct,  
r ef er e nc e pr o d uct or v e hicl e tr e at m e nt gr o u p, r es p ecti v el y, a n d f or a si n gl e 
a p plic ati o n will a p pl y t h e s m all est a m o u nt of t h e st u d y m e dic ati o n n ec ess ar y 
t o a d e q u at el y c o v er e ac h ar e a  of t h e f ac e (c hi n, l eft c h e e k, ri g ht c h e e k, n os e, 
f or e h e a d) 
 a n d a v oi di n g c o nt act wit h t h e e y es ( u p p er a n d 
l o w er  e y eli ds),  li ps,  br o k e n  s ki n,  i nsi d e  t h e  n os e/ n ostrils,  a n d  m uc o us  
m e m br a n es t wic e d ail y , m or ni n g a n d e v e ni n g , (
 
) a p pr oxi m at el y t h e s a m e ti m e  f or 1 2 w e e ks. 
St u d y Visits:  
Cli nic al E v al u ati o ns will b e p erf or m e d at:  
1.  Visit 1/ D a y 1 ( B as eli n e)  
2.  Visit 2/ W e e k 4/ D a y 2 8 ( ± 4 d a ys)  (I nt eri m) 
3.  Visit 3/ W e e k 8/ D a y 5 6 ( ± 4 d a ys)  (I nt eri m) 
4.  Visit 4/ W e e k 1 2/ D a y 8 4 ( ± 4 d a ys)  ( E n d of tr e at m e nt/ E n d st u d y) 
S af et y will b e ass ess e d by m o nit ori n g a d v ers e  e v e nts at e ac h visit a n d at t h e 
W e e k 2/ D a y 1 4  ( ±4  d a ys) T el e p h o n e C o nt act.  

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E v al u ati o ns:  
T h e n u m b er of f aci al i nfl a m m at or y l esi o ns (p a p ul es  a n d p ust ul es ) will b e 
r ec or d e d at b as eli n e a n d e ac h s u bs e q u e nt visit ( Visits 2, 3 a n d 4).  Er yt h e m a 
s e v erit y, t h e I n v esti g at or Gl o b al Ass ess m e nt (I G A) a n d l oc al irrit ati o n will b e 
ass ess e d at B as eli n e a n d all s u bs e q u e nt visits. T h e pr es e nc e of T el a n gi ect asi a 
will b e r ec or d e d at B as eli n e.  
E n d p oi nts:  
T h e pri m ar y effic acy e n d p oi nt will b e t h e  m e a n p erc e nt c h a n g e fr o m b as eli n e 
t o Visit 4/ W e e k 1 2 ( D a y 8 4) i n t h e i nfl a m m at or y ( p a p ul es a n d p ust ul es) l esi o n 
c o u nt.  
 
T h e s ec o n d ar y e n d p oi nt will b e t h e  pr o p orti o n  of s u bj ects wit h cli nic al s ucc ess 
d efi n e d as a sc or e of cl e ar or al m ost cl e ar (sc or e of 0 or 1) o n t h e I n v esti g at or 
Gl o b al Ass ess m e nt (I G A) at Visit 4/ W e e k 1 2  ( D a y 8 4). 
S af et y:  
T h e  i nci d e nc e  of  all  a d v ers e  e v e nts  r e p ort e d  d uri n g  t h e  st u d y  will  b e  
s u m m ariz e d b y tr e at m e nt gr o u p.  S af et y of t h e t est a n d r ef er e nc e will b e 
e v al u at e d b y c o m p ari n g t h e n at ur e, s e v erit y a n d fr e q u e ncy of t h eir a d v ers e 
e v e nt pr ofil es.   

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A B B R E VI A TI O N S  
 
A E  
A dv ers e E v e nt  
A N O V A  
A n al ysis of V ari a nc e  
C M H  
C oc hr a n – M a nt el – H a e nsz el t est  
C R F  
C as e R e p ort F or m  
D C F  
D at a C orr ecti o n F or m  
F D A  
U S F o o d a n d Dr u g A d mi nistr ati o n  
G C P  
G o o d Cli nic al Pr actic es  
I C H 
I nt er n ati o n al C o nf er e nc e o n H ar m o niz ati o n 
I G A 
I nv esti g at or’s Gl o b al Ass ess m e nt 
I R B 
I nstit uti o n al R evi e w B o ar d 
I T T 
I nt e nt- t o-tr e at (p o p ul ati o n ) 
I U 
I nt er n ati o n al U nit 
I U D 
I ntr a-Ut eri n e D evic e  
L O C F 
L ast O bs erv ati o n C arri e d F or w ar d 
M e d D R A  
M e dic al Dicti o n ary f or R e g ul at or y Activiti es  
mI T T  
M o difi e d I nt e nt -to -Tr e at (p o p ul ati o n ) 
N S AI D  
N o n -St er oi d al A nti -I nfl a m m at or y Dr u g  
O T C  
O v er t h e c o u nt er  
PI  
Pri nci p al I nv esti g at or  
P P  
P er - pr ot oc ol (p o p ul ati o n ) 
Rx  
Pr escri pti o n  
S A E  
S eri o us A dv ers e Ev e nt  
S A P  
St atistic al A n alysis Pl a n  
S P F  
S u n Pr ot ecti o n F act or  
S u b -I  
S u b -I nv esti g at or 
U P T  
Uri n e Pr e g n a nc y T est  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.  B A C K G R O U N D  
 
 
   
 
  
 
  
 
  
 
    
 
 
 
    
 
 
 
 
   
 
 
  
 
 
 
 
 
 
Fi n ac e a ® ( Az el aic Aci d f o a m, 1 5 %) is i n dic at e d f or t h e tr e at m e nt of I nfl a m m at or y L esi o ns of R os ac e a.5     
P erri g o U K FI N C O h as d ev el o p e d a g e n eric f or m ul ati o n of Az el aic Aci d f o a m, 1 5 %.  
 
2.  S T U D Y O BJ E C TI V E S  
T h e o bj ecti v es of t his st u d y ar e t o c o m p ar e t h e effic acy a n d s af et y pr ofil es of P erri g o U K FI N C O, Az el aic 
Aci d f o a m, 1 5 %, a n d Fi n ac e a ® ( Az el aic Aci d f o a m, 1 5 %), i n or d er t o s h o w bi o e q ui v al e nc e b et w e e n 
t h e m, a n d t o s h o w t h e s u p eri or effic acy of t h e t w o acti v e f or m ul ati o ns ov er t h at of t h e v e hicl e i n t h e 
tr e at m e nt of I nfl a m m at or y L esi o ns of R os ac e a. 
 
2. 1 E n d p oi nts  
T h e pri m ar y effic acy e n d p oi nt will b e t h e m e a n p erc e nt c h a n g e fr o m b as eli n e t o W e e k 1 2 ( D a y 8 4) i n 
t h e i nfl a m m at or y ( p a p ul es a n d p ust ul es) l esi o n c o u nt.  
 
T h e s ec o n d ar y e n d p oi nt will b e t h e pr o p orti o n of s u bj ects wit h cli nic al s ucc ess d efi n e d as a sc or e of 
cl e ar or al m ost cl e ar (sc or e of 0 or 1) o n t h e I n v esti g at or Gl o b al Ass ess m e nt (I G A) at Visit 4/ W e e k 1 2.  
 
2. 2 S af et y  
S af et y of t h e t est a n d r ef er e nc e pr o d ucts will b e c o m p ar e d b y e v al u ati n g t h e n at ur e, s e v erit y a n d 
fr e q u e ncy of t h eir a d v ers e e v e nt pr ofil es.  All a d v ers e e v e nts t h at occ ur d uri n g t h e st u d y will b e 

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V ersi o n 2. 0 D at e: Oct o b er 0 4, 2 0 1 6                                                                   A m e n d m e nt # 1  
 
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r ec or d e d. D escri pti o ns of r e acti o ns or c o m pl ai nts will i nclu d e t h e a p pr oxi m at e d at e of o ns et, t h e d at e 
t h e a d v ers e e v e nt e n d e d, t h e s e v erit y of t h e a d v ers e e v e nt, a n d t h e o utc o m e.  C o m p aris o ns b et w e e n 
t h e tr e at m e nt gr o u ps will b e m a d e b y t a b ul ati n g t h e fr e q u e ncy of su bj ects wit h o n e or m or e a d v ers e 
e v e nts (cl assif i e d i nt o M e d D R A t er ms) d uri n g t h e st u d y. P e ars o n’s C hi-S q u ar e t est or Fis h er’s Ex act 
t est, w hic h e v er is m ost a p pr o pri at e, will b e us e d t o c o m p ar e t h e pr o p orti o n of s u bj ects i n e ac h 
tr e at m e nt gr o u p wit h a ny a d v ers e e v e nt.  T h e a dv ers e e v e nts r e p ort e d b y at l e ast fi v e p erc e nt of t h e 
s u bj ects i n a n y tr e at m e nt gr o u p will b e s u m m ariz e d d escri pti v el y. 
 
3. S T U D Y D E SI G N  
 
3. 1 T y p e/ D esi g n of St u d y  
S u bj ects i n t his m ulti -c e nt er, d o u bl e-bli n d, r a n d o miz e d, v e hicl e -c o ntr oll e d, p ar all el-gr o u p st u d y will 
b e assi g n e d i n a 
 t o t est pr o d uct, r ef er e nc e pr o d uct, or v e hicl e, r es p ecti v el y.  
 
 will b e a p pli e d t o pic all y 
as a t hi n l a y er  t o a d e q u at el y c o v er  e ac h ar e a of t h e f ac e (c hi n, l eft c h e e k, ri g ht c h e e k, n os e, a n d 
f or e h e a d), a v oi di n g c o nt act wit h t h e e y es ( u p p er a n d l o w er e y eli ds), li ps, br o k e n s ki n, i nsi d e t h e 
n os e/ n ostrils a n d m uc o us m e m br a n es , t wic e d aily m or ni n g a n d e v e ni n g (
 
) a p pr oxi mat el y t h e s a m e ti m e f or 1 2 w e e ks.   
 
Visits t o t h e st u d y sit e ar e sc h e d ul e d at B as eli n e ( D a y 1) a n d W e e ks 4, 8, a n d 1 2.  A t el e p h o n e c o nt act 
will b e m a d e at W e e k 2/ D a y 1 4.  
 
3. 2 St u d y P o p ul ati o n  
S u bj ects will b e m al es a n d f e m al es, at l e ast 1 8 y e ars of a g e, wit h at l e ast m o d er at e p a p ul o p ust ul ar 
f aci al r os ac e a wit h a n i nfl a m m at or y l esi o n ( p a p ul es a n d p ust ul es) 
, i ncl usi v e, o n t h e 
f ac e i ncl u di n g t h os e pr es e nt o n t h e n os e, at l e ast m od er at e er yt h e m a a n d pr es e nc e of t el a n gi ect asi a.   
 
4.  S EL E C TI O N A N D WI T H D R A W AL O F S T U D Y S U BJ E C T S  
 
4. 1 I ncl usi o n Crit eri a 
S u bj ects m ust  m e et all of t h e f oll o wi n g crit eri a:  
 
1.  S u bj ect m ust si g n a n I nstit uti o n al R e vi e w B o ar d (I R B) a p pr o v e d writt e n i nf or m e d c o ns e nt f or t his 
st u d y.  
 
 
2.  S u bj ects m ust b e  h e alt hy m al es or f e m al es  at l e ast 1 8  y e ars of a g e. S u bj ects m ust b e i n g e n er al 
g o o d h e alt h a n d fr e e fr o m a n y cli nic all y si g ni fic a nt dis e as e, ot h er t h a n r os ac e a, t h at mi g ht i nt erf er e 
wit h t h e st u d y e v al u ati o ns.  
3.  S u bj ects m ust h a v e a d efi nit e cli nic al di a g n osis of m o d er at e  f aci al p a p ul o p ust ul ar r os ac e a , d efi n e d 
as t h e pr es e nc e of:  
a)  A 
 i nfl a m m at or y l esi o ns ( p a p ul es a n d p ust ul es) 
i ncl u di n g t h os e pr es e nt o n t h e n os e. 

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P a g e 1 1  of 5 3  
 
b) At l e ast m o d er at e p ersist e nt er yt h e m a, A N D  
c) T el a n gi ect asi a. 
4.  
 
  
5.  
 
 
6.  
 
  
•  
 
 
 
 
 
 
 
 
 
 
 
 
. 
7.  S u bj ects m ust b e willi n g t o mi ni miz e c o ntr oll a bl e ext er n al f act ors t h at mi g ht tri g g er r os ac e a fl ar e -
u ps  (
 
) t hr o u g h o ut t h eir 
p artici p ati o n i n t h e  st u d y. 
8.  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
. 
 
4. 2 E x cl usi o n Crit eri a 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 1 2  of 5 3  
 
S u bj ects m a y n ot  b e s el ect e d if a n y of t h e f oll o wi n g crit eri a exist:  
 
1.  S u bj ects, w h o ar e pr e g n a nt, br e astf e e di n g, or pl a n ni n g a pr e g n a ncy wit hi n t h e  p eri o d of t h eir st u d y  
p artici p ati o n . 
2.  
. 
3.  C urr e nt  or p ast oc ul ar r os ac e a  ( e. g., c o nj u ncti vitis, bl e p h aritis, or k er atitis) of s uffici e nt  s e v erit y t o 
r e q uir e t o pic al or s yst e mic a nti bi otics. 
4.  S u bj ects wit h is ol at e d a n d/ or m o d er at e t o s e v er e r hi n o p h y m a, d e ns e t el a n gi ect as es or pl a q u e -li k e 
f aci al e d e m a. 
5.  Pr es e nc e of a n y ot h er f aci al s ki n c o n diti o n t h at mi g ht i nt erf er e wit h r os ac e a di a g n osis a n d / or 
ass ess m e nt 
 
 
 
 
 
 
. 
6.  A n y u nc o ntr oll e d, c hr o nic or s eri o us dis e as e or m e dic al c o n diti o n t h at w o ul d pr e v e nt p artici p ati o n 
i n a cli nic al tri al or, i n j u d g m e nt of t h e I n v esti g at or, w o ul d p ut t h e s u bj ect at u n d u e ris k or mi g ht 
c o nf o u n d t h e st u d y ass ess m e nts (s uc h as pl a n n e d h os pit aliz ati o ns d uri n g t h e st u d y).  
7.  Exc essi v e f aci al h air ( e. g., b e ar ds, si d e b ur ns, m o ust ac h es, etc.) t h at w o ul d i nt erf er e wit h di a g n osis 
or ass ess m e nt of r os ac e a.  
8.  
 
9.  
. 
1 0.  
 
1 1.  Hist or y of h y p ers e nsiti vity or all er g y t o a z el aic aci d , a n d/ or a n y i n gr e di e nt i n t h e st u d y m e dic ati o n  
( e. g., pr o p yl e n e gl yc ol) .  
1 2.  Us e wit hi n 6 m o nt hs  ( 1 8 0 d a ys) pri or t o b as eli n e or d uri n g t h e st u d y of or al r eti n oi ds ( e. g., 
Acc ut a n e ®)  or t h er a p e utic vit a mi n A s u p pl e m e nts of gr e at er t h a n 1 0, 0 0 0 u nits/ d a y ( m ulti vit a mi ns 
ar e all o w e d).  
1 3.  
 
1 4.  
 
 
 
1 5.  
 
 
 
 
 
  
1 6.  Us e of m e dic at e d m a k e -u p  (
) t hr o u g h o ut t h e st u d y a n d si g nific a nt 
c h a n g e i n t h e us e of c o ns u m er pr o d ucts wit hi n 3 0 d a ys  of st u d y e ntr y a n d t hr o u g h o ut t h e st u d y.  

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P a g e 1 3  of 5 3  
 
1 7.  
 
 
 
1 8.  Us e wit hi n 3 0 d a ys  ( 1 m o nt h) pri or t o b as eli n e or d uri n g t h e st u d y of 1) s yst e mic st er oi ds * * , 2) 
t o pic al r eti n oi ds t o t h e f ac e, 3) s yst e mic ( e. g., or al or i nj ect a bl e) a nti bi otics k n o w n t o i m p act o n 
t h e s e v erit y of f aci al r os ac e a ( e. g., cycli n es a n d its d eri v ati v es, t etr acycli n e a n d its d eri v ati v es , 
er yt hr o m yci n  a n d its d eriv ati v es , d oxycycli n e a n d its d eri v ati v es, mi n ocycli n e a n d its d eri v ati v es,  
m acr oli d es  a n d its d eri v ati v es,  azit hr o m yci n a n d its d eri v ati v es, cl arit hr o m yci n a n d its d eri v ati v es,  
m etr o ni d az ol e a n d its d eri v ati v es,   s ulf a m et h ox a d ol e, b actri m or tri m et h o pri m ); s h ort t er m 
tr e at m e nt of all ot h er a nti bi otics ( n ot aff ecti n g r os ac e a  f or) ≤ 1 4 d a ys f or n o n -r os ac e a r el at e d 
c o n diti o ns is acc ept a bl e , 4) i m m u n os u p pr essi v e a g e nts, or i m m u n o m o d ul at ors. 
•  
 
 
•  
 
 
•  
. 
•  
 
1 9.  
 
 
 
 
 
2 0.  
 
 
 
 
 
 
2 1.  
 
.  
2 2.  S u bj ect c o ns u m es exc essi v e alc o h ol, a b us es dr u gs, or h as a c o n diti o n t h at c o ul d c o m pr o mis e t h e 
s u bj ect’s a bilit y t o c o m ply wit h st u d y r e q uir e m e nts a n d/ or h a v e dr u g or alc o h ol a d dicti o n r e q uiri n g 
tr e at m e nt i n t h e p ast 1 2 m o nt hs. 
2 3.  
  
 
 
2 4.  
 
  
2 5.  P artici p ati o n i n a ny cli nic al st u dy i nv olvi n g a n i n v esti g ati o n al pr o d uct, a g e nt or d evic e  t h at mi g ht 
i nfl u e nc e t h e i nt e n d e d eff ects or m as k t h e si d e eff ects of st u d y m e dic ati o n i n t h e 1 m o nt h ( 3 0 
d a ys) pri or Visit 1/ D a y 1 ( B as eli n e) or t hr o u g h o ut t h e st u d y.  
2 6.  
 
 

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P a g e 1 4  of 5 3  
 
2 7.  
 
  
2 8.  
 
 
2 9.  
 
 
 
3 0.  
.  
3 1.  S u bj ects w h o i n t h e o pi ni o n of t h e i n v esti g at or, ar e u nli k el y t o b e a bl e t o f oll o w t h e r estricti o ns of 
t h e pr ot oc ol a n d c o m pl et e t h e st u d y.  
 
4. 3 Pr o hi bit e d M e dic ati o ns  
T h e f oll o wi n g m e dic ati o ns/ pr oc e d ur es ar e p r o hi bit e d d uri n g t his st u d y: 
1.  Us e of a n y tr e at m e nt f or r os ac e a ot h er t h a n t h e assi g n e d st u d y tr e at m e nt . 
2.  
 
.  
•  
 
 
 
 
 
.  
3.  Us e  of  s yst e mic a nti -r os ac e a dr u gs,  s yst e mic  r eti n oi ds,  s yst e mic  c ortic ost er oi ds,  or  
i m m u n os u p pr essi v e dr u gs or i m m u n o m o d ul at ors , t h er a p e utic vit a mi n A s u p pl e m e nts of gr e at er 
t h a n 1 0, 0 0 0 u nits/ d a y ar e pr o hi bit e d d uri n g t his st u d y.  
4.  
 
•  
d.  
•  
 
. 
•  
 
5.  Us e of s yst e mic a nti bi otics  ( e. g., or al or i nj ect a bl e) k n o w n t o i m p act o n t h e s e v erit y of r os ac e a 
i ncl u di n g,  b ut  n ot  li mit e d  t o,  cycli n es  a n d  its  d eri v ati v es,  t etr acycli n e  a n d  its  d eri v ati v es,  
er yt hr o m yci n a n d its d eri v ati v es, d oxycli n e a n d its d eri v ati v es, mi n ocycli n e a n d its d eri v ati v e, 
m acr oli d es a n d  its d eri v ati v es, azit hr o m yci n a n d its d eri v ati v es, cl arit hr o myci n a n d its d eri v ati v es, 
m etr o niz a d ol e a n d its d eri v ati v es, s ulf a m et h ox a d ol e, b actri m a n d tri m et h o pri m ar e pr o hi bit e d 
d uri n g t his st u d y.  S h ort t er m tr e at m e nt of all ot h er a nti bi otics ≤ 1 4 d a ys f or n o n-r os ac e a r el at e d 
c o n diti o ns is acc e pt a bl e. 
6.  Us e of t o pic al a nti bi otics, ot h er r os ac e a dr u gs, r eti n oi ds or c ortic ost er oi ds a p pli e d t o t h e f ac e ar e 
pr o hi bit e d d uri n g t his st u d y.  
7.  Us e of or al r eti n oi ds is pr o hi bit e d d uri n g t h e st u dy.  
8.  A p plic ati o n  of  t o pic al  astri n g e nts  or  a br asi v es  e. g.,  r u bs,  exf oli ati n g  cl e a ns ers  a n d  pr o d ucts  

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P a g e 1 5  of 5 3  
 
c o nt ai ni n g S alicylic aci d a n d/ or alc o h ol b as e d t o n ers, astri n g e nts; t o pic al pr e p ar ati o ns t h at c o nt ai n 
s pic es or li m e, or m e dic at e d t o pic al pr e p ar ati o ns ( pr escri pti o n a n d O T C pr o d ucts) t o t h e f ac e.  
9.  Us e of a br asi v e cl e a ns ers or w as h es ( e. g., exf oli ati n g f aci al scr u bs) a n d a d h esi v e cl e a nsi n g stri ps 
( e. g., Bi or é ® P or e Stri ps) o n t h e f ac e.  
1 0.  
 
 
 
 
 
 
  
1 1.  
 
 
1 2.  Us e of t a n ni n g b o ot hs, s u n l a m ps, s a u n a, s u n b at hi n g or ot h er exc essi v e ex p os ur e t o s u nli g ht 
s h o ul d b e a v oi d e d. 
1 3.  M e dici n es  a n d/ or  pr o d ucts  t h at  m a y  i ncr e as e  s e nsiti vit y  t o  s u nli g ht  ( a p art  fr o m  t h e  st u d y  
m e dic ati o n) s h o ul d b e us e d d uri n g t his st u d y o nl y aft er c o ns ult ati o n wit h t h e I n v esti g at or.  
1 4.  Us e of h or m o n al c o ntr ac e pti v es s h o ul d n ot b e i niti at e d or c h a n g e d d uri n g t h e st u d y.  
 
 
4. 4 Pr ec a uti o ns  
T h e f oll o wi n g pr ec a uti o ns ar e t o b e t a k e n d uri n g t his st u d y:  
1.  S u bj ects s h o ul d a v oi d c o nt act of t h e st u d y m e dic ati o n wit h t h e e y es  ( u p p er a n d l o w er e y eli ds), 
i nsi d e t h eir n os e/ n ostrils, m uc o us m e m br a n es a n d  li ps, or o n a n y c uts or br o k e n s ki n. I n c as e of 
acci d e nt al ex p os ur e, t h e e y es s h o ul d b e ri ns e d wit h pl e nt y of w at er a n d a p h ysici a n s h o ul d b e 
c o ns ult e d if e y e irrit ati o n p ersists. 
2.  A v oi d fir e, fl a m e, or s m oki n g d uri n g a n d i m m e di at el y f oll o wi n g a p plic ati o n of t h e  st u d y m e dic ati o n 
si nc e t h e pr o p ell a nt i n t h e st u d y m e dic ati o n is fl a m m a bl e. 
3.  T h e a er os ol c a nist er s h o ul d n ot b e p u nct ur e d or i nci n er at e d. 
4.  T h e pr o d uct s h o ul d n ot b e a p pli e d t o c uts, a br asi o ns, ecz e m at o us or s u n b ur n e d s ki n, or sit es ot h er 
t h a n t h e tr e at m e nt ar e a.  
5.  S u bj ects s h o ul d w as h t h eir h a n ds b ef or e a n d i m m e di at el y aft er a p pl yi n g st u d y m e dic ati o n.  
6.  
 
 
s.  
7.  
 
 
8.  T h e st u d y m e dic ati o n s h o ul d b e s pr e a d s m o ot hl y a n d 
 o n t h e f ac e (f or e h e a d, 
c hi n, a n d n os e, l eft a n d ri g ht c h e e k); exc essi v e r u b bi n g m ust b e a v oi d e d.  
9.  T h e st u d y m e dic ati o n s h o ul d n ot b e a p pli e d m or e t h a n t wic e d ail y a n d s u bj ects s h o ul d n ot us e 
m or e t h a n t h e r ec o m m e n d e d a m o u nt o n t h e e ntir e f ac e (
 
). 

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P a g e 1 6  of 5 3  
 
1 0.  
. 
1 1.  S u bj ects s h o ul d n ot a p pl y m oist uriz ers  (
), 
m e dic at e d m a k e -u p ( i ncl u di n g n e w br a n ds), cr e a ms, l oti o ns, p o w d ers or a n y t o pic al pr o d uct ot h er 
t h a n t h e st u d y m e dic ati o n t o t h e f ac e. 
1 2.  
 
  
1 3.  S u bj ects s h o ul d li mit s u n ex p os ur e, i ncl u di n g s u nl a m ps ( n o n -pr escri pti o n U V li g ht s o urc es); a v oi d 
t a n ni n g b e ds/ b o ot hs/ p arl ors a n d s a u n a w hil e usi n g t h e pr o d uct. 
1 4.  S u bj ect s h o ul d us e a n y ty p e of s u nscr e e n a n d pr ot ecti v e a p p ar el ( e. g. , wi d e -bri m m e d h at) w h e n 
o ut d o ors. W e at h er  extr e m es,  s uc h  as  wi n d  or  c ol d,  m a y  b e  irr it ati n g  t o  s u bj ects  r ec ei vi n g  
tr e at m e nt. 
1 5.  
.  
1 6.  
 
 
 
 
1 7.  
 
. 
1 8.  S u bj ects s h o ul d c o ns ult t h e i n v esti g at or wit h a n y q u esti o ns r e g ar di n g c o nc o mit a nt m e dic ati o ns.  
1 9.  
 
 
2 0.  
. 
2 1.  
 
.   
2 2.  S u bj ect s h o ul d a v oi d a n y f o o ds a n d b e v er a g es t h at mi g ht pr o v o k e er yt h e m a, fl us hi n g, a n d bl us hi n g 
 
 t hr o u g h o ut t h e st u d y. 
 
5.  
P R O C E D U R E S  
 
5. 1 S u bj ect Scr e e ni n g a n d E nr oll m e nt  
T h e st u d y p ers o n n el will r e vi e w t h e I R B a p pr o v e d i nf or m e d c o ns e nt f or m wit h e ac h s u bj ect a n d gi v e 
t h e s u bj ect a n o p p ort u nit y t o h a v e all q u esti o ns a ns w er e d b ef or e pr oc e e di n g.  T h e c o ns e nt f or m m ust 
b e si g n e d b y e ac h s u bj ect a n d wit n ess e d b ef or e t h e s u bj ect is e nr oll e d i nt o t h e st u d y.  T h e wit n ess c a n 
b e a n y o n e pr es e nt d uri n g t h e si g ni n g of t h e c o ns e nt f or m ot h er t h a n t h e i n di vi d u al ex pl ai ni n g t h e 
c o ns e nt.  A c o p y of t h e si g n e d c o ns e nt will  b e gi v e n t o e v er y p artici p a nt ( or l e g all y a ut h oriz e d 
r e pr es e nt ativ e ) a n d t h e ori gi n al will b e m ai nt ai n e d wit h t h e p artici p a nt’s r ec or ds.    
 
 
 
 
5. 2 Assi g n m e nt of S u bj ect N u m b er  

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P a g e 1 7  of 5 3  
 
 
  T h e s u bj ect n u m b er will c orr es p o n d t o a c o m p ut er-g e n er at e d r a n d o miz ati o n 
sc h e d ul e assi g ni n g t h e n u m b er t o o n e of t h e t hr e e st u d y tr e at m e nt gr o u ps.  
 
O nc e t h e s u bj ect h as c o ns e nt e d  a n d  m et i ncl usi o n/ excl us i o n crit eri a, t h e y will b e assi g n e d a s u bj ect 
n u m b er. T h e s u bj ect n u m b er will b e t a k e n fr o m t h e st u d y m e dic ati o n kit dis p e ns e d t o t h e s u bj ect at 
e ac h sit e.  
 
5. 3 D e m o gr a p hics/ M e dic al Hist or y  
A  d e m o gr a p hic  pr ofil e  a n d  c o m pl et e  m e dic al  hist or y  will  b e  r ec or d e d pri or  t o  st arti n g  st u d y  
m e dic ati o n .  T h e m e dic al hist or y will i ncl u d e a c o m pl et e r e vi e w of all c urr e nt dis e as es a n d t h eir 
r es p ecti v e tr e at m e nts. 
 
5. 4 C o nc o mit a nt M e dic ati o ns  
C o nc o mit a nt m e dic ati o ns a n d a n y m e dic ati o ns t ak e n i n t h e  
 pri or t o si g ni n g i nf or m e d c o ns e nt 
will b e r ec or d e d as pri or/c o nc o mit a nt m e dic ati o ns ( usi n g t h eir g e n eric n a m e, if k n o w n) wit h t h e 
c orr es p o n di n g i n dic ati o n. T h e m e dic ati o ns t o b e r ec or d e d will i ncl u d e pr escri pti o n a n d o v er -t h e-
c o u nt er ( O T C) m e dic ati o ns a n d di et ar y s u p pl e m e nts.  All m e dic ati o ns t a k e n o n eit h er a r e g ul ar or “ pr n” 
b asis, i ncl u di n g vit a mi ns, as piri n a n d ac et a mi n o p h e n, s h o ul d b e r ec or d e d o n t his p a g e pri or t o st arti n g 
st u d y m e dic ati o n. A r ec or d of m e dic ati o n t a k e n b y t h e s u bj ect d uri n g t h e st u d y is t o b e o bt ai n e d at 
e ac h st u d y visit i ncl u di n g t h e W e e k 2/ D a y 1 4 ( ± 4  d a ys) t el e p h o n e c o nt act.  
 
5. 5 P h ysic al E x a mi n ati o n  
T h e i n v esti g at or, s u b -i n v esti g at or or a p pr o pri at ely d el e g at e d a n d q u alifi e d d esi g n e e will p erf or m a 
bri ef p h ysic al ex a mi n ati o n pri or t o t h e s u bj ect st arti n g st u d y m e dic ati o n o n B as eli n e/ D a y 1 .
 
 
 
 
 
5. 6 Uri n e Pr e g n a nc y T est  
A uri n e pr e g n a ncy t est will b e c o n d uct e d at Visit 1/ B as eli n e ( b ef or e t h e s u bj ect a p pli es t h e first d os e 
of t h e  st u d y m e dic ati o n at t h e sit e) a n d at  e ac h s u bs e q u e nt visit . A n i n v esti g at or m a y r e p e at t h e 
pr e g n a ncy t est a n yti m e d uri n g t h e st u d y if t h er e is a n y s us pici o n or p ossi bilit y t h at t h e s u bj ect m a y b e 
pr e g n a nt. 
 
 
 
 
 
 
 
 
 
 
 

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P a g e 1 8  of 5 3  
 
 
 
 
  
 
5. 7 D er m at ol o gic al Ass ess m e nt ( Di a g n osis)  
T h e I n v esti g at or or s u b-i n v esti g at or will ex a mi n e t h e s u bj ect t o est a blis h t h e cli nic al di a g n osis of 
p a p ul o p ust ul ar  f aci al  r os ac e a  
 
. 
 
5. 8 I n v esti g at or’s Gl o b al Ass ess m e nt (I G A) 
T o t h e gr e at est ext e nt p ossi bl e, t h e s a m e i n v esti g at or w h o m a d e b as eli n e ( D a y 1) ass ess m e nts will 
p erf or m a Gl o b al Ass ess m e nt of t h e s u bj ect’s o v er all r os ac e a c o n diti o n at e ac h s u bs e q u e nt visit.  
 
At Visit 1/ B as eli n e ( D a y 1), t h e i n v esti g at or s h o ul d p erf or m t h e I G A b ef or e t h e s u bj ect a p pli es t h e first 
d os e of t h e st u d y m e dic ati o n at t h e sit e.  
 
 
 
 
.  
 
T h e f oll o wi n g sc al e will b e us e d f or t h e I n v esti g at or’s Gl o b al Ass ess m e nt:  
 
Gr a d e  
C at e g or y  
D escri pti o n  
0 
Cl e ar  
Cl e ar s ki n wit h n o i nfl a m m at or y  l esi o ns ( p a p ul es or p ust ul es) or 
n o d ul es ; at m ost, mil d eryt h e m a.  
1 
Al m ost 
Cl e ar  
V er y f e w s m all p a p ul es or p ust ul es . V er y mil d er yt h e m a pr es e nt . 
2 
Mil d  
S e v erit y  
S e v er al s m all p a p ul es or p ust ul es . Mil d er yt h e m a 
3 
M o d er at e  
S e v erit y  
S e v er al s m all or l ar g e p a p ul es or p ust ul es, a n d u p t o 2 n o d ul es . 
M o d er at e er yt h e m a.  
4  
S e v er e  
N u m er o us s m all a n d/ or l ar g e p a p ul es or p ust ul es, u p t o s e v er al 
n o d ul es . S e v er e er yt h e m a. 
 
5. 9 E v al u ati o n of Tr e at m e nt Ar e a  
T h e i n v esti g at or s h o ul d e v al u at e  t h e tr e at m e nt ar e a b ef or e a s u bj ect a p pli es t h e first d os e of st u d y 
m e dic ati o n. E ac h s u bj ect’s i niti al c o n diti o n a n d c o urs e of r os ac e a will b e ass ess e d b y t h e f oll o wi n g: 1) 
c o u nti n g t h e i nfl a m m at or y ( p a p ul es a n d p ust ul es ) a n d n o d ul es i ncl u di n g t h os e pr es e nt o n t h e n os e 
a n d d oc u m e nti n g o n t h e f aci al di a gr a m ( 
 as p art of t h e s o urc e d oc u m e nt ati o n, 2) r ati n g 
t h e s e v erit y of er yt h e m a, 3) pr es e nc e/ a bs e nc e of t el a n gi ect asi a ( e v al u at e d at Visit 1/ B as eli n e o nly), 
a n d 4) e v al u ati o n of t h e a p plic at i o n sit e r e acti o n. 
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 1 9  of 5 3  
 
 
 
 
 
5. 9. 1 I nfl a m m at or y L esi o n C o u nt ( P a p ul es a n d P ust ul es) 
T h e n u m b ers of i nfl a m m at or y l esi o ns (f aci al p a p ul es a n d  p ust ul es ) a n d n o d ul es , l oc at e d a b o v e t h e j a w 
li n e t o t h e h airli n e i ncl u di n g t h ose pr es e nt o n t h e n os e, ar e t o b e c o u nt e d at b as eli n e  ( b ef or e t h e 
s u bj ect a p pli es t h e first d os e of t h e st u d y m e dic ati o n at t h e sit e) a n d at e ac h s u bs e q u e nt visit. T h e 
t y p e a n d n u m b er of e ac h l esi o n is t o b e r ec or d e d o n t h e s o urc e d oc u m e nt at e ac h visit a nd t h e t ot al 
c o u nt of p a p ul es a n d p ust ul es r ec or d e d ( excl u di n g n o d ul es).  
 
P a p ul e = s oli d p al p a bl e i nfl a m m at or y l esi o n ≤ 5 m m di a m et er  
 
P ust ul e = p us -fill e d i nfl a m m at or y l esi o n ≤ 5 m m i n di a m et er 
 
N o d ul e  = p al p a bl e s oli d or s oft l esi o n > 5 m m i n di a m et er  
 
C o u nts of n o d ul es s h o ul d b e r e p ort e d s e p ar at el y a n d n ot i ncl u d e d i n i nfl a m m at or y l esi o n c o u nts.  
S u bj ects wit h m or e t h a n 2 f aci al n o d ul es at b as eli n e s h o ul d b e excl u d e d fr o m t h e st u d y.   
 
5. 9. 2 Er yt h e m a S e v erit y Ass ess m e nt  
 
At Visit 1/ B as eli n e ( D a y 1), t h e i n v esti g at or s h o ul d p erf or m t h e er yt h e m a ass ess m e nt b ef or e t h e 
s u bj ect a p pli es t h e first d os e of t h e st u d y m e dic ati o n at t h e sit e. 
 
T h e s e v erit y of er yt h e m a is t o b e r at e d as f oll o ws:  
 
S C O R E  
A S S E S S M E N T  
D E S C RI P TI O N  
0  
N o n e  
N o r e d n ess pr es e nt  
1  
Mil d  
Sli g ht pi n k n ess t o li g ht r e d 
2  
M o d er at e  
D efi nit e r e d n ess, e asil y r ec o g niz e d  
3  
S e v er e  
M ar k e d er yt h e m a; fi er y r e d  
 
5. 9. 3 T el a n gi ect asi a E v al u ati o n  
 
T h e pr es e nc e or a bs e nc e of t el a n gi ect asi a is t o b e e v al u at e d at Visit  1/ B as eli n e o nl y  pri or t o first st u d y 
d os e m e dic ati o n a p plic ati o n . 
 
5. 1 0 A p plic ati o n Sit e R e acti o n Ass ess m e nt  
 
At Visit 1/ B as eli n e ( D a y 1) a n d e ac h s u bs e q u e nt visit, a p plic ati o n sit e r e acti o ns s uc h as  dr y n ess, 
b ur ni n g/sti n gi n g, pr urit us  a n d sc ali n g/ p e eli n g, a n d p ai n ar e t o b e r ec or d e d o n t h e s o urc e d oc u m e nt . 
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 2 0  of 5 3  
 
At Visit 1/ B as eli n e ( D a y 1), t h e i n v esti g at or s h o ul d p erf or m t h e a p plic ati o n sit e r e acti o n ass ess m e nt 
b ef or e a n d 
 aft er t h e s u bj ect a p pli es t h e first d os e of t h e st u d y m e dic ati o n 
at t h e sit e.  
 
T h e A p plic ati o n Sit e R e acti o n Ass ess m e nt  m ust b e c o n d uct e d b y q u alifi e d i n v esti g at ors list e d o n t h e 
F or m F D A 1 5 7 2 w h o h av e b e e n d el e g at e d t h es e t as ks b y t h e PI. 
 
 
.  
 
 
 
•  
.  
•  
. 
•  
. 
 
 
 
 
T h e i n v esti g at or will ass ess a s u bj ect’s a p plic ati o n sit e r e acti o n b y r ati n g t h e f oll o wi n g s y m pt o ms 
acc or di n g t o t h e sc al es pr o vi d e d b el o w .  Pr urit us a n d sti n gi n g/ b ur ni n g s y m pt o ms will b e ass ess e d b y 
disc ussi o n wit h t h e s u bj ect a n d will b e r e p ort e d as t h e s e v erit y ex p eri e nc e d wit hi n 2 4 h o urs of t h e 
st u d y visit.     
 
Dr y n ess : Mil d sc ali n g, r o u g h n ess, f e eli n g of ti g ht n ess, a n d p ossi bl y itc hi n g  
S C O R E  
A S S E S S M E N T  
D E S C RI P TI O N  
0  
N o n e  
 
1  
Mil d  
 
2  
M o d er at e  
 
3  
S e v er e  
 
 
Sc ali n g/ P e eli n g:  S ki n d es q u a m ati o n; s h e d di n g of t h e o ut er l a y ers of t h e s ki n  
S C O R E  
A S S E S S M E N T  
D E S C RI P TI O N  
0  
N o n e  
 
1 
Mil d  
 
2  
M o d er at e  
 
3  
S e v er e  
 
 
Pr urit us:  Itc hi n g 
S C O R E  
A S S E S S M E N T  
D E S C RI P TI O N  
0  
N o n e  
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 2 1  of 5 3  
 
1  
Mil d  
 
2 
M o d er at e  
 
 
3 
S e v er e  
 
 
 
Sti n gi n g/ B ur ni n g:   Sti n gi n g/ti n gli n g s e ns ati o n  
S C O R E  
A S S E S S M E N T  
D E S C RI P TI O N  
0  
N o n e  
 
1  
Mil d  
 
2 
M o d er at e  
 
. 
3 
S e v er e  
 
 
 
P ai n:   P ai n, u n pl e as a nt s e ns ati o n c a usi n g disc o mf ort s uc h as ti n gli n g, pric ki n g  ( pi ns a n d n e e dl es) 
a n d/ or t e n d er n ess  
S C O R E  
A S S E S S M E N T  
D E S C RI P TI O N  
0  
N o n e  
 
1  
Mil d  
 
2  
M o d er at e  
 
3  
S e v er e  
 
 
5. 1 1 St u d y M e dic ati o n Us e, S u bj ect I nstr ucti o ns a n d Di ar y  
At t h e b as eli n e visit, o n e  ( 1), 
 a er os ol  c a nist er of st u d y m e dic ati o n fr o m t h e s u bj ect kit b ox will 
b e dis p e ns e d , b y t h e t hir d p art y dis p e ns er (if p ossi bl e) or d esi g n e e , t o e nr oll e d s u bj ects al o n g wit h a 
di ar y c ar d.  E ac h s u bj ect will als o r ec ei v e a c o py of writt e n i nstr ucti o ns, w hic h d et ail t h e pr o p er 
a p plic ati o n  m et h o d,  a n d  g e n er al  i nstr ucti o ns  r e g ar di n g  t h e  st u d y  (
). At  Visit  
1/ B as eli n e/ D a y 1, t h e t hir d p art y dis p e ns e r (if p ossi bl e) or d esi g n e e s h o ul d e ns ur e t h at all s u bj ects m et 
eli gi bilit y  crit eri a  a n d  all  effic aci es  (I G A,  Er yt h e m a,  T el a n gi ect asi a)  a n d  s af et y  ( a p plic ati o n  sit e  
r e acti o ns) ass ess m e nts ar e c o n d uct e d b y t h e i n v esti g at or b ef or e t h e s u bj ects p erf or m t h e i niti al 
a p plic ati o n.  T h e i niti al a p plic ati o n o n D a y 1 will b e p erf or m e d b y t h e s u bj ect a n d o bs er v e d b y st u d y 
st aff at t h e st u d y sit e d uri n g t h e st u d y visit t o e ns ur e s u bj ects u n d erst a n d t h e i nstr ucti o ns  a n d ar e 
a p pl yi n g t h e m e dic ati o n a p pr o pri at el y .  
 
 T h e p u m p of t h e a er os ol c a n ist er s h o ul d b e d e pr ess e d g e ntl y t o dis p e ns e t h e s m allest  
a m o u nt of t h e f o a m n ec ess ar y t o c o v er e ac h f aci al ar e a (c hi n, l eft c h e e k, ri g ht c h e e k, n os e, a n d 
f or e h e a d) f or e ac h si n gl e a p plic ati o n. T h e pr o p ell a nt i n t h e st u d y m e dic ati o n is fl a m m a bl e. T h er ef or e, 
fir e, fl a m e or s m o ki n g d uri n g a n d i m m e di at el y f oll o wi n g t h e a p plic ati o n of t h e st u d y m e dic ati o n s h o ul d 
b e a v oi d e d.  
 
. S u bs e q u e nt a p plic ati o ns of st u d y m e dic ati o n s h o ul d b e a p pli e d as 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 2 2  of 5 3  
 
i nstr uct e d b y t h e s u bj ect at h o m e m or ni n g a n d e v e ni n g (
).  T h e 
st u d y st aff s h o ul d i nstr uct t h e s u bj ect t o a p pl y all s u bs e q u e nt d os es of t h e st u d y m e dic ati o n t wic e 
d ail y , m or ni n g a n d e v e ni n g  
 b ef or e b e dti m e . S u bj ects will a p pl y t h e s ec o n d d os e of 
t h e m e dic ati o n i n t h e ev e ni n g o n D a y 1 if first d os e w as a p pli e d i n t h e m or ni n g o n D a y 1 or i n t h e 
m or ni n g of D a y 2 if first d os e w as a p pli e d i n t h e aft er n o o n/ e v e ni n g o n D a y 1 .  At all s u bs e q u e nt st u d y 
visits t h e st u d y m e dic ati o n will b e c oll ect e d t o ass ess  c o m pli a nc e a n d st u dy m e dic ati o n acc o u nt a bilit y.  
Aft er t h e c o m pli a nc e e v al u ati o n, e m pt y a e r os ol c a nist er will b e c oll ect e d a n d k e pt b y t h e sit e.  A er os ol 
c a nist ers wit h  r e m ai ni n g m e dic ati o n will b e  r e dis p e ns e d t o t h e s u bj ect. 
 
 
 
 
 
 
. T h e st u d y m e dic ati o n kits m ust b e 
st or e d (i n a n u pri g ht p ositi o n) i n a s ec ur e d ar e a wit h li mit e d acc ess, at 2 5° C ( 7 7° F); exc ursi o ns 
p er mitt e d b et w e e n 1 5° C t o 3 0° C ( 5 9° F t o 8 6° F) u ntil dis p e ns e d t o t h e s u bj ect.  O nc e dis p e ns e d t o t h e 
s u bj ect t h e st u d y m e dic ati o n will b e st or e d i n a n u pri g ht p ositi o n at 2 5° C ( 7 7° F) .  
 
S u bj ects will cl e a ns e t h eir f ac e wit h a mil d cl e a ns er usi n g o nl y t h eir h a n ds a n d p at dr y wit h a s oft cl e a n 
t o w el.   
. F or a si n gl e 
a p plic ati o n, t h e  “s m all est” a m o u nt of t h e st u d y m e dic ati o n n ec ess ar y will  b e a p pli e d 
 t o 
a d e q u at el y c o v er e ac h ar e a of t h e f ac e (c hi n, l eft c h e e k, ri g ht c h e e k, n os e, f or e h e a d) a n d a v oi di n g 
c o nt act wit h t h e e y es ( u p p er a n d l o w er e y eli ds), li ps, br o k e n s ki n, i nsi d e t h e n os e/ n ostril a n d m uc o us 
m e m br a n es, t wic e  d ail y  i n  t h e  m or ni n g  a n d  ev e ni n g  (
),  at  
a p pr oxi m at el y t h e s a m e ti m e f or 1 2 w e e k s.  (
 
) S u bj ects 
s h o ul d b e i nstr uct e d t o w as h h a n ds i m m e di at el y aft er a p pl yi n g t h e st u d y m e dic ati o n.  S u bj ects  s h o ul d 
c o nti n u e t o us e a mil d cl e a ns er t o w as h t h e f ac e f or t h e d ur ati o n of t h e st u d y. S u bj ects will b e 
i nstr uct e d t o n ot us e a n y ot h er t o pic al tr e at m e nts or pr o d ucts (a n y t y p e of s u nscr e e n is all o w e d) ot h er 
t h a n t h e st u d y m e dic ati o n o n t h eir f ac e.  
 
A di ar y c ar d will b e dis p e ns e d t o e ac h e nr oll e d s u bj ect at Visits 1, 2 & 3.  T h e s u bj ects will b e i nstr uct e d 
t o c o m pl et e t h e di ar y c ar d aft er a p pl yi n g e ac h d os e of st u d y m e dic ati o n  i n t h e m or ni n g a n d e v e ni n g 
d ail y .  At e ac h s u bs e q u e nt visit, st u d y p ers o n n el will r e vi e w a n d c oll ect t h e di ar y c ar d, d et er mi n e 
w h et h er t h e s u bj ect r e q uir es c o u ns eli n g f or d os a g e c o m pli a nc e, c o nfir m a n d r ec or d us e of a n y 
pr o hi bit e d m e dic ati o ns, ass ess A Es, dis p e ns e a d diti o n al st u d y m e dic ati o n a n d a n e w di ar y  as r e q uir e d .  
I n a d diti o n, e ac h st u d y s u bj ect will b e r e mi n d e d t o bri n g wit h t h e m all pr e vi o usl y dis p e ns e d a er os ol 
c a nist ers (r e g ar dl ess of c o nt e nt) a n d t h e c o m pl et e d di ar y c ar d at t h e n ext visit.  St u d y p ers o n n el will 
sc h e d ul e t h e s u bj ect’s n ext visit pri or t o t h e s u bj ect’s d ep art ur e.  
 
5. 1 2 Visit S p ecific Pr oc e d ur es  
T h e f oll o wi n g s ecti o ns o utli n e t h e pr oc e d ur es r e q uir e d at e ac h visit.  
 
5. 1 2. 1 B as eli n e Visit  1/ D a y 1 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 2 3  of 5 3  
 
Pr os p ecti v e s u bj ects will visit t h e st u d y c e nt er a n d b e ex a mi n e d b y t h e st u d y p h ysici a n  w h o will 
p erf or m t h e pr oc e d ur es b el o w at t his visit .  
 
T h e f oll o wi n g pr oc e d ur es : I nf or m e d C o ns e nt, I ncl usi o n/ Excl usi o n Crit eri a, M e dic al 
Hist or y/ D e m o gr a p hics, c oll ecti o n a n d r e vi e w of C o nc o mit a nt m e dic ati o ns, P h ysic al ex a m, Vit al si g ns, 
d er m at ol o gic al ass ess m e nt  ( di a g n osis), e v al u ati o n of t h e tr e at m e nt ar e a, I G A, er yt h e m a ass ess m e nt,  
e v al u ati o n  t el a n gi ect asi a a n d Uri n e pr e g n a ncy t est m ust b e c o m pl et e d a n d d oc u m e nt e d o n t h e 
s o urc e d oc u m e nt b ef or e a s u bj ect is r a n d o miz e d o n t h e st u d y. 
 
 
 
 
 
•  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 1 2. 2 T el e p h o n e C o nt act/ W e e k 2/ D a y 1 4 ( ± 4 d a ys)  
•  
 
 
 
 
 
 
 
 
 
5. 1 2. 3 Visit 2/ W e e k 4/ D a y 2 8 ( ± 4 d a ys)  
•  
 
 
 
 
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 2 4  of 5 3  
 
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 1 2. 4 Vi sit 3/ W e e k 8/ D a y 5 6 ( ± 4 d a ys) 
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 1 2. 5 Visit 4/ W e e k 1 2/ D a y 8 4 ( ± 4 d a ys) E n d of Tr e at m e nt/ E arl y T er mi n ati o n Visit  
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 1 2. 6 U nsc h e d ul e d Visit  
A n u nsc h e d ul e d visit is all o w e d at a n y ti m e  if i n t h e i n v esti g at or’s o pi ni o n it is w arr a nt e d.  If t h e 
i n v esti g at or ass ess es t h e s u bj ect’s c o n diti o n a n d d et er mi n es t h at t h e s u bj ect’s c o n diti o n h as w ors e n e d 
t o t h e d e gr e e t h at it is u ns af e f or t h e s u bj ect t o c o nti n u e i n t h e st u d y, t h e s u bj ect m a y b e disc o nti n u e d 
fr o m t h e st u d y as a tr e at m e nt f ail ur e, a n E arl y T er mi n ati o n Visit c o n d uct e d, a n d a st a n d ar d of c ar e 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 2 5  of 5 3  
 
tr e at m e nt m a y b e a d vis e d at t h e i n v esti g at or’s discr eti o n. T h e
 
 
 
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 1 3 S u m m ar y  of Ass ess m e nts  
T h e sc h e d ul e of visits a n d pr oc e d ur es t o b e c o n d uct e d at e ac h visit ar e s u m m ariz e d i n t h e Sc h e d ul e 
of St u d y Pr oc e d ur es.  
 
Visit 1/ B as eli n e/ D a y 1  
 
 Th e f oll o wi n g pr oc e d ur es :  I nf or m e d C o ns e nt, I ncl usi o n/ Excl usi o n Crit eri a, M e dic al Hist or y  
/ D e m o gr a p hics, c oll ecti o n a n d r e vi e w of C o nc o mit a nt m e dic ati o ns, P h ysic al ex a m, Vit al si g ns, 
d er m at ol o gic al ass ess m e nt  ( di a g n osis), e v al u ati o n of t h e tr e at m e nt ar e a, I G A, er yt h e m a ass ess m e nt,  
e v al u ati o n t el a n gi ect asi a  a n d Uri n e pr e g n a ncy t est  m ust b e c o m pl et e d a n d d oc u m e nt e d o n t h e 
s o urc e d oc u m e nt b ef or e a s u bj ect is r a n d o miz e d o n t h e st u d y. 
 
T h e s af et y ( a p plic ati o n sit es r e acti o ns ) ass ess m e nts m ust b e c o m pl et e d pri or t o  a n d 
 
aft er  t h e first st u d y m e dic ati o n a p plic ati o n .   
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 2 7  of 5 3  
 
eSt u d y m e dic ati o n t o b e c oll ect e d a n d/ or dis p e ns e d, if n ec ess ar y  
 fU P T  t o b e c o n d uct e d at U nsc h e d ul e d Visit, if a p plic a bl e 
* *  A p plic ati o n sit es r e acti o ns m ust b e c o m pl et e d pri or t o a n d a p pr oxi m at el y t hirt y ( 3 0) mi n ut es aft er t h e first st u d y m e dic ati o n 
a p plic ati o n  
* * * O nc e t h e a er os ol c a nist er is o p e n e d a n d us e d at l e ast o nc e , it ex pir es 8 w e eks l at er 
 
 
5. 1 4 Scr e e n F ail ur es  
Scr e e n f ail ur es will n ot b e e nt er e d i n t h e d at a b as e n or  i ncl u d e d i n a n y d at a a n al ys es.  A scr e e n f ail ur e 
is a s u bj ect w h o r ec ei v e d i nf or m ati o n a b o ut t h e st u d y, i ncl u di n g si g ni n g a n i nf or m e d c o ns e nt, a n d 
p ossi bl y p erf or mi n g s o m e st u d y r el at e d pr oc e d ur es, b ut w as n ot e nr oll e d, dis p e ns e d a n d a p pli e d t h e 
i n v esti g ati o n al pr o d uct. 
 
5. 1 5  Pr ot oc ol D e vi ati o ns/ Vi ol ati o ns  
T his st u d y will b e c o n d uct e d as d escri b e d i n t his pr ot oc ol exc e pt f or a n e m er g e ncy sit u ati o n i n w hic h 
t h e pr ot ecti o n, s af et y, a n d w ell-b ei n g of t h e s u bj ect r e q uir es i m m e di at e i nt er v e nti o n, b as e d o n t h e 
ju d g m e nt of t h e i n v esti g at or or a r es p o nsi bl e, a p pr o pri at el y tr ai n e d a n d cr e d e nti al e d pr of essi o n al(s) 
d esi g n at e d b y t h e i n v esti g at or. I n t h e e v e nt of a si g nific a nt d e vi ati o n fr o m t h e pr ot oc ol d u e t o a n 
e m er g e ncy, acci d e nt or mist a k e, t h e i n v esti g at or or d es i g n e e m ust c o nt act P erri g o / 
 c o nt acts 
i n S ecti o n 1 5 ( A p p e n dix A) at t h e e arli est p ossi bl e ti m e. 
 
 
 
 
 
 
  
 
 
 
 
 
 
.  
 
5. 1 6 S u bj ect/ Tr e at m e nt C o m pli a nc e  
S u bj ects will a p pl y t h e s m all est a m o u nt of t h e st u d y m e dic ati o n o n e ac h ar e a of t h e f ac e (c hi n, l eft 
c h e e k, ri g ht c h e e k, n os e, a n d f or e h e a d) i n t h e m or ni n g a n d  e v e ni n g (
 
) t wic e d ail y f or 1 2 w e e ks. O n D a y 1, s u bj ects will a p pl y t h eir i niti al d os e of st u d y m e dic ati o n 
a t t h e st u d y sit e
 
 
. O n W e ek 2/ D a y 1 4 ( ± 4 d a ys), c o m pli a nc e will b e ass ess e d vi a t el e p h o n e c o nt act. T h e 
st u d y c o or di n at or, or d esi g n e e, will r e vi e w t h e S u bj ect I nstr ucti o n S h e et a n d Di ar y wit h t h e s u bj ect o n 
t h e p h o n e. T h e t ot al n u m b er of st u d y m e dic ati o n d os es a p pli e d a n d/ or miss e d wi ll b e d et er mi n e d 
b as e d u p o n t h e first d os e a p pli e d t hr o u g h a n d i ncl u di n g t h e l ast d os e a p pli e d. T h e first a n d l ast d at es 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 2 8  of 5 3  
 
of tr e at m e nt s h o ul d b e r ec or d e d o n t h e C R F. T h e t ot al n u m b er of st u d y m e dic ati o n d os es a p pli e d a n d 
miss e d s h o ul d als o b e r ec or d e d.  By d efi niti o n , t h er e ar e n o miss e d a p plic ati o ns b ef or e t h e first d at e 
of tr e at m e nt or aft er t h e l ast d at e of tr e at m e nt.
 
 
  All us e d a n d 
u n us e d a er os ol c a nist ers of st u d y m e dic ati o n will b e c oll ect e d b y t h e st u d y sit e at a p pr o pri at e visits or 
e arl y t er mi n ati o n.  
 
5. 1 7 Disc o nti n u ati o n/ Wit h dr a w al of St u d y S u bj ects  
S u bj ects m a y b e r e m o v e d fr o m t h e st u d y f or a n y of t h e f oll o wi n g r e as o ns:  
•  T h e s u bj ect wit h dr a ws his or h er c o ns e nt f or a n y r e as o n.  
•  T h e s u bj ect’s c o n diti o n h as w ors e n e d t o t h e d e gr e e t h at t h e i n v esti g at or f e els it is u ns af e  
  f or t h e s u bj ect t o c o nti n u e i n t h e st u d y or r e q uir es a n alt er n ati v e t h er a py . 
•  T h e s u bj ect’s m e dic ati o n c o d e is u n bli n d e d.  
•  S u bj ect di d n ot m e et , or n o l o n g er m e ets , t h e e ntr y crit eri a. 
•  A n a d v ers e e v e nt , i ncl u di n g i nt erc urr e nt ill n ess, occ urs f or w hic h t h e s u bj ect d esir es t o 
disc o nti n u e tr e at m e nt or t h e i n v esti g at or d et er mi n es t h at it is i n t h e s u bj ect’s b est i nt er est 
t o b e disc o nti n u e d. 
•  T h e s u bj ec t is l ost t o f oll o w-u p.  T h e i n v esti g at or will d oc u m e nt eff orts t o att e m pt t o r e ac h 
t h e s u bj ect t wic e b y t el e p h o n e a n d will s e n d a c ertifi e d f oll o w-u p l ett er b ef or e c o nsi d eri n g 
t h at s u bj ect l ost t o f oll o w-u p. All att e m pts m ust b e t h or o u g hl y r ec or d e d.  
•  T h e s u bj ect b ec o m es pr e g n a nt d uri n g t h e c o urs e of t h e tri al.  
•  L ac k of effic acy (tr e at m e nt f ail ur e) aft er 1 m o nt h ( 3 0 d a ys) of tr e at m e nt wit h a c o m pli a nc e 
r at e of  
 (i n v esti g at or r e m o v al fr o m st u d y). 
•  I n v esti g at or discr eti o n ( e. g., n o n-c o m pli a nt t o st u d y pr ot oc ol r e q uir e m e nts). 
 
Aft er a s u bj ect h as b e e n disc o nti n u e d, h e/s h e will n ot b e all o w e d t o r e -e nr oll i n t h e st u d y at a n y 
f acilit y.  
 
T h e r e as o n(s) f or a s u bj ect b ei n g disc o nti n u e d fr o m t h e st u d y will b e d oc u m e nt e d i n t h e C R F a n d t h e 
e nr oll m e nt l o g.  
 
If a s u bj ect is disc o nti n u e d fr o m t h e st u d y f or a n y r e as o n, t h e Visit 4 ( D a y 8 4)/ E n d of St u d y Visit/ E arl y 
T er mi n ati o n Visit pr oc e d ur es s h o ul d b e c o m pl et e d a n d a n y o utst a n di n g d at a a n d st u d y m e dic ati o n 
s h o ul d b e c oll ect e d.  D at a, i n a d diti o n t o t h e r e as o n f or disc o nti n u ati o n a n d t h e d at e of r e m o v al, will 
b e r ec or d e d o n t h e S o urc e D oc u m e nt a n d E n d of St u d y C R F.  
 
I n t h e e v e nt t h at a s u bj ect disc o nti n u es fr o m t h e st u d y at a n y ti m e d u e t o a n a d v ers e e v e nt, t h e r e as o n 
f or disc o nti n u ati o n, t h e n at ur e of t h e e v e nt a n d its cli nic al c o urs e m ust b e f ull y d oc u m e nt e d.  F or s uc h 
a s u bj ect, t h e i n v esti g at or m ust stri v e t o f oll o w t h e s u bj ect u ntil t h e a d v ers e e v e nt h as r es ol v e d, 
b ec o m e
 cli nic all y
 i nsi g nific a nt,
 is
 st a biliz e d,
 or
 t h e
 s u bj ect
 is
 l ost
 t o
 f oll o w -u p.  
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 2 9  of 5 3  
 
 
 
 
  
 
6. M A T E RI AL S A N D S U P PLI E S  
 
6. 1 St u d y M e dic ati o n  
T h e st u d y m e dic ati o n s u p pli e d b y P erri g o will c o nsist of:  
 
T est Pr o d uct :  Az el aic Aci d F o a m, 1 5 %,  
P erri g o
 
 
 
R ef er e nc e  Pr o d uct :   Fi n ac e a® ( Az el aic  aci d  f o a m,  1 5 %)  M a n uf act ur e d  b y  B a y er  H e alt h C ar e 
P h ar m ac e utic als I nc.  
 
V e hicl e :  V e hicl e of t est pr o d uct  
(
.) 
 
6. 2 M e dic ati o n M a n a g e m e nt  
 
6. 2. 1 L a b eli n g, P ac k a gi n g a n d Distri b uti o n 
T h e st u d y m e dic ati o n assi g n e d t o e ac h s u bj ect n u m b e r will b e d et er mi n e d b y a c o m p ut er-g e n er at e d 
r a n d o miz ati o n sc h e d ul e.  St u d y m e dic ati o n is l a b el e d a n d p ac k a g e d, acc or di n g t o t h e r a n d o miz ati o n 
c o d e, s o t h at n eit h er t h e s u bj ect n or t h e i n v esti g at or c a n i d e ntif y t h e tr e at m e nt.    
 
 
 
 
 
 
  
 
 
 
 
T h e t e ar -off p orti o n of e ac h kit l a b el c o nt ai ns t h e i d e ntit y of t h e m e dic ati o n i n t h e a er os ol c a nist er. 
T h e i n v esti g at or will n ot r e m o v e t h e occl u di n g l a y er of t h e l a b el u nl ess a bs ol ut el y n ec ess ar y t o pr o vi d e 
m e dic al tr e at m e nt t o a s u bj ect i n a n e m er g e ncy a n d pr ef er a bl y wit h pri or a ut h oriz ati o n fr o m P erri g o 
or d esi g n e e, w h e n e v er p ossi bl e.  If t h e occl u d e d p orti o n of t h e l a b el is r e m o v e d, e ac h i n v olv e d 
s u bj ect(s) will b e disc o nti n u e d fr o m t h e st u d y a n d t h e r e as o n will b e n ot e d o n t h e s o urc e d oc u m e nt 
a n d C R Fs . 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 0  of 5 3  
 
 
T h e t e ar -off p orti o n h as a n a d h esi v e b ac ki n g t o affix t o t h e st u d y m e dic ati o n dis p e nsi n g l o g t h at will 
b e m ai nt ai n e d at t h e i n v esti g at or sit e.  
 
 
 
 
 
 
  
 
 
T h e i n v esti g at or p erf or mi n g t h e cli nic al e v al u ati o ns will n ot dis p e ns e or c oll ect st u d y m e dic ati o n.  
 
6. 2. 2 R et e nti o n S a m pl es  
E ac h i n v esti g ati o n al sit e w h er e st u d y m e dic ati o n is dis p e ns e d t o at l e ast o n e s u bj ect will b e r e q uir e d 
t o ra n d o ml y s el ect o n e bl oc k  (
) of st u d y m e dic ati o n t o b e 
m ai nt ai n e d as r et ai n s a m pl es.  T h e i n v esti g at or will m ai nt ai n o n e r a n d o ml y s el ect e d bl oc k of st u d y 
m e dic ati o n fr o m e ac h s hi p m e nt  of st u d y m e dic ati o n r ec ei v e d.  As p er t h e C o d e of F e d er al R e g ul ati o ns 
P art 2 1, S ecti o n 3 2 0. 3 8( e), “ E ac h r es er v e s a m pl e s h all b e st or e d u n d er c o n diti o ns c o nsist e nt wit h 
pr o d uct l a b eli n g a n d i n a n ar e a s e gr e g at e d fr o m t h e ar e a w h er e t esti n g is c o n d uct e d a n d wit h acc ess 
li mit e d t o a ut h oriz e d p ers o n n el  ( at r o o m t e m p er at ur e, 2 5° C ( 7 7° F); exc ursi o ns p er mitt e d b et w e e n 
1 5° C t o 3 0° C ( 5 9° F a n d 8 6° F) e v e n aft er t h e st u d y h as c o ncl u d e d. E ac h r es er v e s a m pl e s h all b e r et ai n e d 
f or a p eri o d of at l e ast 5 y e ars f oll o wi n g t h e d at e o n w hic h t h e a p plic ati o n or s u p pl e m e nt al a p plic ati o n 
is a p pr o v e d, or, if s uc h a p plic ati o n or s u p pl e m e nt al a p plic ati o n is n ot a p pr o v e d, at l e ast 5 y e ars 
f oll o wi n g t h e d at e of c o m pl eti o n of t h e bi o a v ail a bilit y st u d y i n w hic h t h e s a m pl e fr o m w hic h t h e 
r es er v e s a m pl e w as o bt ai n e d or w as us e d.” T h e i n v esti g at or will st or e t h e r et ai ne d  s a m pl e st u d y 
m e dic ati o n u ntil s uc h ti m e of n otific ati o n is r ec ei v e d fr o m P erri g o t h at t h e s a m pl es ar e n o l o n g er 
r e q uir e d. 
 
6. 2. 3 St or a g e a n d T est Articl e Acc o u nt a bilit y  
St u d y m e dic ati o n  us e d t o c o n d uct t his st u d y will b e m ai nt ai n e d u n d er a d e q u at e s ec urit y b y t h e 
i n v esti g at or or d esi g n e e. E ac h i n v esti g at or sit e will e ns ur e t h at t h e t e m p er at ur e of st u d y m e dic ati o n 
is m o nit or e d a n d r ec or d e d t hr o u g h o ut t h e st u d y. T h e st u d y m e dic ati o n s h o ul d n ot b e fr oz e n,  ex p os e d 
to h e at , or st or e d at t e m p er at ur es a b o v e 1 2 0° F ( 4 9 ° C). T h e st u d y m e dic ati o n s h o ul d b e st or e d at r o o m 
t e m p er at ur e i n a s ec ur e d ar e a wit h li mit e d acc ess, 2 5° C ( 7 7° F); exc ursi o ns p er mitt e d b et w e e n 1 5° C t o 
3 0° C ( 5 9° F t o 8 6° F) a n d a er os ol c a nist er s k e pt i n a n u pri g ht p ositi o n a n d ti g htl y cl os e d. T h e i n v esti g at or 
or d esi g n e e will i nstr uct s u bj ects t o st or e t h e st u d y m e dic ati o n i n a s ec ur e ar e a at r o o m t e m p er at ur e 
at 2 5° C ( 7 7°F), o ut of r e ac h of c hil dr e n, a er os ol c a nist er s ar e n ot t o b e ex p os e d t o h e at  or t e m p er at ur e 
a b o v e 1 2 0° F ( 4 9° C) , p u nct ur e d or i nci n er at e d. T h e i n v esti g at or will n ot s u p pl y st u d y m e dic ati o n t o a n y 
p ers o n n ot e nr oll e d  i n  t his  st u d y,  or t o  a n y  p h ysici a n  or sci e ntist exc e pt t h os e n a m e d  as s u b -
i n v esti g at ors.  
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 1  of 5 3  
 
T h e cli nic p ers o n n el at e ac h i n v esti g at or sit e will k e e p a r u n ni n g i n v e nt or y of st u d y m e dic ati o n  
dis p e ns e d t h at will i ncl u d e s u bj ect n u m b ers assi g n e d a n d t h e d at e e ac h a er os ol c a nist er of st u d y 
m e dic ati o n is dis p e ns e d a n d r et ur n e d.  A st u d y m e dic ati o n acc o u nt a bilit y f or m will b e pr o vi d e d t o t h e 
i n v esti g at or t o d oc u m e nt all m e dic ati o ns r ec ei v e d, dis p e ns e d b y a n d us e d b y e ac h s u bj ect.  At t h e 
c o ncl usi o n of t h e st u d y all u n us e d, p arti all y us e d, a n d e m pt y a er os ol c a nist er s m ust b e i n v e nt ori e d b y 
t h e m o nit or a n d r et ur n e d t o P erri g o, or d esi g n e e, f or d estr ucti o n, wit h t h e exc e pti o n of r et e nti o n 
s a m pl es w hic h s h all r e m ai n at t h e I n v esti g at or sit e. 
 
6. 2. 4 R a n d o miz ati o n  
R a n d o miz ati o n will b e p erf or m e d acc or di n g t o a c o m p ut er g e n er at e d r a n d o miz ati o n sc h e m e w h er e 
t h e tr e at m e nt gr o u p d esi g n ati o n h as b e e n assi g n e d t o t h e s u bj ect n u m b er.  T h e tr e at m e nt d esi g n ati o n 
will r e m ai n bli n d e d u ntil t h e fi n al d at a b as e is l oc k e d.  A n i n d e p e n d e nt t hir d p art y will h ol d t h e 
r a n d o miz ati o n c o d e t hr o u g h o ut t h e st u d y.  T h e r a n d o miz ati o n sc he m e will b e a bl oc k r a n d o miz ati o n, 
wit h e ac h bl oc k 
. 
 
6. 2. 5 Pr oc e d ur e f or Br e a ki n g t h e Bli n d  
T h e i n v esti g at or, st aff at t h e st u d y sit e, st u d y m o nit ors, a n d d at a a n al ysis/ m a n a g e m e nt p ers o n n el ar e 
bli n d e d t o t h e s u bj ect assi g n m e nt. I n t h e e v e nt of a n e m er g e ncy, t h e s p ecific s u bj ect tr e at m e nt m a y 
b e i d e ntifi e d b y r e m o vi n g t h e o v erl a y of t h e bli n d e d l a b el f or e ac h s u bj ect at e ac h i n v esti g at or sit e, 
w hic h is att ac h e d t o t h e st u d y m e dic ati o n l o g; h o w e v er, e v er y eff ort s h o ul d b e m a d e t o m ai nt ai n t h e 
bli n d.  T h e i n v esti g at or m ust n ot scr atc h off t h e occl u di n g l a y er of t h e l a b el u nl ess a bs ol ut el y 
n ec ess ar y t o pr o vi d e m e dic al tr e at m e nt t o a s u bj ect i n a n e m er g e nc y sit u ati o n o nl y a n d s h o ul d s e e k 
pri or a ut h oriz ati o n b y P erri g o or d esi g n e e w h e n p ossi bl e.  T h e r e as o n f or br e a ki n g t h e bli n d m ust b e 
cl e arl y d oc u m e nt e d i n t h e s o urc e d oc u m e nt ati o n a n d C R F a n d t h e s u bj ect m ust b e disc o nti n u e d fr o m 
t h e st u d y. P erri g o m ust b e n otifi e d i m m e di at el y u p o n all u n bli n di n g sit u ati o ns.  
 
7.  A D V E R S E R E A C TI O N S  
T h e p ot e nti al a d v ers e r e acti o ns of g e n eric  Az el aic Aci d F o a m , 1 5 % ar e a ntici p at e d t o b e si mil ar t o 
t h os e o bs er v e d i n Fi n ac e a ® (Az el aic Aci d ) F o a m, 1 5 %.  
 
T h e f oll o wi n g a d v ers e r e acti o ns occ urr e d i n gr e at er t h a n  0. 5 % of p ati e nts tr e at e d wit h Az el aic Aci d 
F o a m, 1 5 %,  a p plic ati o n sit e p ai n ( 6. 2 % ) , d escri b e d as b ur ni n g, sti n gi n g, “ pi ns a n d n e e dl es”, a n d/ or 
t e n d er n ess , a p plic ati o n sit e er yt h e m a ( 0. 7 %), a p plic a ti o n sit e dr y n ess ( 0. 7 %), a n d a p plic ati o n sit e 
pr urit us ( 2. 5 %).  
 
Is ol at e d r e p orts of l oss of s ki n c ol or ( h y p o pi g m e nt ati o n) h a v e b e e n  r e p ort e d f oll o wi n g t o pic al us e of 
Fi n ac e a ®.  Fi n ac e a ® h as n ot b e e n w ell st u di e d i n p ati e nts wit h d ar k c o m pl exi o n. T h er ef or e,  s u bj ects 
wit h d ar k er c o m pl exi o n s h o ul d b e m o nit or e d cl os el y f or e arl y si g ns of l oss of s ki n c ol or b y t h e 
i n v esti g at ors  a n d  i nstr uct e d  t o  r e p ort  i m m e di at el y  a n y  a b n or m al  c h a n g es  i n  s ki n c ol or  t o  t h e  
i n v esti g at ors.  W h e n si g nific a nt h y p o pi g m e nt ati o n ar e r e p ort e d b y s u bj ects, st u d y m e dic ati o n s h o ul d 
b e disc o nti n u e d.   
 
Az el aic aci d h as b e e n r e p ort e d t o c a us e irrit ati o n of t h e e y es a n d m uc o us m e m br a n e irrit ati o n. C o nt act 
wit h t h e st u d y pr o d uct s h o ul d b e a v oi d e d o n t h e  e y es, m o ut h a n d ot h er m uc o us m e m br a n es a n d if 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 2  of 5 3  
 
t h er e is c o nt act wit h t h e e y es, l ar g e a m o u nts of w at er s h o ul d b e us e d t o w as h t h e e y es a n d s u bj ects 
s h o ul d b e i nstr uct e d t o c o ns ult a p h ysici a n if e y e irrit ati o n p ersists.  
 
Hy p ers e nsiti vit y , r as h a n d w ors e ni n g of ast h m a  h a v e  b e e n r e p ort e d i n p ost -m ar k eti n g us e of pr o d ucts 
c o nt ai ni n g Az el aic aci d -c o nt ai ni n g f or m ul ati o ns.   
 
7. 1 D e p art ur e fr o m t h e Pr ot oc ol f or I n di vi d u al S u bj ects  
W h e n a n e m er g e ncy occ urs r e q uiri n g a d e p art ur e fr o m t h e pr ot oc ol f or a s u bj ect, d e p art ur e will b e 
o nl y f or t h at s u bj ect.  I n s uc h circ u mst a nc es, t h e i n v esti g at or or ot h er p h ysici a n i n att e n d a nc e will 
c o nt act t h e M e dic al M o nit or or P erri g o b y t el e p h o n e a n d f oll o w u p wit h a writt e n d escri pti o n as s o o n 
as p ossi bl e.  T h e o v ers e ei n g I R B s h o ul d als o b e n otifi e d.  
 
7. 2 D efi niti o ns  
A n a d v ers e e v e nt ( A E) is d efi n e d as a n y u nt o w ar d m e dic al occ urr e nc e i n a s u bj ect a d mi nist er e d a 
m e dici n al  pr o d uct  a n d  w hic h  d o es  n ot  n ec ess aril y  h a v e  t o  h a v e  a  c a us al  r el ati o ns hi p  wit h  t his 
tr e at m e nt. A n a d v ers e ev e nt c a nist er t h er ef or e b e a n y u nf a v or a bl e a n d u ni nt e n d e d si g n (f or ex a m pl e, 
a n  a b n or m al  l a b or at or y  fi n di n g),  s y m pt o m,  or  dis e as e  t e m p or all y  ass oci at e d  wit h  t h e  us e  of  a  
m e dici n al pr o d uct, w h et h er or n ot c o nsi d er e d r el at e d t o t his m e dici n al pr o d uct.  
 
A s eri o us a d v ers e e v e nt ( S A E) is a n a d v ers e e v e nt t h at r es ults i n a n y of t h e f oll o wi n g o utc o m es: 
•  D e at h  
•  Lif e-t hr e at e ni n g e v e nt (i. e., t h e s u bj ect w as, i n t h e o pi ni o n of t h e i n v esti g at or, at i m m e di at e ris k 
of d e at h fr o m t h e e v e nt as i t occ urr e d.  It d o es n ot i ncl u d e a n e v e nt t h at, h a d it occ urr e d i n a 
m or e s e v er e f or m, mi g ht h a v e c a us e d d e at h .) 
•  R e q uir es i n -s u bj ect h os pit aliz ati o n or pr ol o n gs h os pit aliz ati o n 
•  A p ersist e nt or si g nific a nt dis a bilit y/i nc a p acit y or s u bst a nti al disr u pti o n of t h e a bilit y t o c o n d uct 
n or m al lif e f u ncti o ns  
•  C o n g e nit al a n o m al y/ birt h d ef ect  
•  Ot h er  a d v ers e  e v e nts  t h at  m a y  b e  c o nsi d er e d  s eri o us  b as e d  u p o n  a p pr o pri at e  m e dic al  
j u d g m e nt, m a y j e o p ar diz e t h e s u bj ect a n d m a y r e q uir e m e dic al or s ur gic al i nt er v e nti o n t o 
pr e v e nt o n e of t h e o utc o m es list e d a b o v e.  
 
I m m e di at el y  R e p ort a bl e  A d v ers e  E v e nts  (I R A E): A n y  s eri o us  A E  or  a n y  A E  t h at  n ec essit at es  
disc o nti n u ati o n of st u d y m e dic ati o n, i ncl u di n g pr e g n a ncy.  
 
U n ex p ect e d A d v ers e E v e nt :  A n u n ex p ect e d e v e nt  is a n y a d v ers e dr u g ex p eri e nc e, t h e s p ecificit y or 
s e v erit y of w hic h is n ot c o nsist e nt wit h t h e c urr e nt a p pr o v e d pr o d uct l a b eli n g ( p ac k a g e i ns ert) f or t h e 
st u d y m e dic ati o n, t h e I n v esti g at or’s Br oc h ur e, or as d escri b e d i n t h e cli nic al pr ot o c ol a n d c o ns e nt 
m at eri als.    
 
I nt e nsit y of A d v ers e E v e nts:  T h e m axi m u m i nt e nsit y of a n A E d uri n g a d ay s h o ul d b e r ec or d e d o n t h e 
C R F. If t h e i nt e nsit y of a n A E c h a n g es o v er a n u m b er of d a ys, t h e n s e p ar at e e ntri es s h o ul d b e m a d e 
h a vi n g disti nct o ns et d at es f or t h e c h a n g es i n s e v erit y.  
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 3  of 5 3  
 
Mil d - A Es ar e us u all y tr a nsi e nt, r e q uiri n g n o s p eci al tr e at m e nt, a n d d o n ot i nt erf er e wit h 
s u bj ect’s d ail y acti viti es. 
 
M o d er at e - A Es t y pic all y i ntr o d uc e a l o w l e v el of i nc o n v e ni e nc e or c o nc er n t o t h e s u bj ect a n d 
m a y i nt erf er e wit h d ail y acti viti es, b ut ar e us u all y a m eli or at e d b y si m pl e t h er a p e utic m e as ur es.  
 
S e v er e - A Es i nt err u pt a s u bj ect’s us u al d ail y acti vit y a n d tr a diti o n all y r e q uir e s yst e mic dr u g 
t h er a p y or ot h er tr e at m e nt. 
 
C a us al R el ati o ns hi p t o  St u d y M e dic ati o n:   Th e f oll o wi n g crit eri a s h o ul d b e us e d i n ass essi n g t h e 
a p p ar e nt c a us al r el ati o ns hi p of a n A E t o st u d y m e dic ati o n.  
 
D efi nit el y - T h e A E:  
• 
f oll o ws a r e as o n a bl e t e m p or al s e q u e nc e fr o m st u d y m e dic ati o n a d mi nistr ati o n 
• 
a b at es u p o n disc o nti n u ati o n of t h e st u d y m e d ic ati o n ( d ec h all e n g e) 
• 
is c o nfir m e d b y r e a p p e ar a nc e of t h e r e acti o n o n r e p e at ex p os ur e. 
 
Pr o b a bl y - T h e A E:  
• 
f oll o ws a r e as o n a bl e t e m p or al s e q u e nc e fr o m st u d y m e dic ati o n a d mi nistr ati o n 
• 
a b at es u p o n disc o nti n u ati o n of t h e st u d y m e dic ati o n ( d ec h all e n g e)  
• 
c a n n ot b e r e as o n a bl y ex pl ai n e d b y t h e k n o w n c h ar act eristics of t h e s u bj ect’s st at e.  
 
P ossi bl e - T h e A E:  
• 
f oll o ws a r e as o n a bl e t e m p or al s e q u e nc e fr o m st u d y m e dic ati o n a d mi nistr ati o n 
• 
b ut c o ul d r e a dil y b e pr o d uc e d b y a n u m b er of ot h er f act ors.  
 
U nli k el y - T h e A E:  
•  f oll o ws a r e as o n a bl e t e m p or al s e q u e nc e fr o m st u d y m e dic ati o n a d mi nistr ati o n. 
•  c o ul d h a v e b e e n pr o d uc e d b y eit h er t h e s u bj ect’s cli nic al st at e or b y st u d y m e dic ati o n 
a d mi nistr ati o n.  
 
N ot r el at e d - T h e A E:  
•  d o es n ot h a v e a r e as o n a bl e t e m p or al ass oci ati o n wit h t h e a d mi nistr ati o n of st u d y m e dic ati o n  
•  h as s o m e ot h er o b vi o us ex pl a n ati o n f or t h e e v e nt.  
 
 
7. 3 Eliciti n g a n d R e p orti n g of A d v ers e E v e nts  
T h e i n v esti g at or will p eri o dic all y ass ess s u bj ects f or t h e occ urr e nc e of a d v ers e e v e nts. 
 
 
 
 All a d v ers e e v e nts ( as d efi n e d i n S ecti o n 7. 2), eit h er 
o bs er v e d b y t h e I n v esti g at or or o n e of his/ h er m e dic al c oll a b or at ors, or r e p ort e d b y t h e p artici p a nt 
s p o nt a n e o usl y, or i n r es p o ns e t o dir ect q u esti o ni n g, will b e r e p ort e d a n d d oc u m e nt e d i n t h e s o urc e 
a n d t h e s t u d y r e p orti n g f or ms. W h e n r e p orti n g a n a d v ers e e v e nt, t h e I n v esti g at or m ust assi g n a 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 4  of 5 3  
 
s e v erit y gr a d e t o e ac h ev e nt a n d d ecl ar e a n o pi ni o n o n t h e r el at e d n ess of t h e e v e nt t o t h e st u d y 
m e dic ati o n or pr oc e d ur e.  S eri o us or u n ex p ect e d a d v ers e e v e nts m ust b e r e p ort e d t o P erri g o wit hi n 
2 4 h o urs  of w h e n t h e I n v esti g at or first l e ar ns of t h e occ urr e nc e of t h e e v e nt.  
 
A d v ers e e v e nts will b e d oc u m e nt e d i n t h e s o urc e d oc u m e nt a n d r ec or d e d i n a ti m el y m a n n er o n c as e 
r e p ort f or ms ( C R Fs).  A d v ers e e v e nts t h at ar e i d e ntifi e d at t h e l ast ass ess m e nt visit ( or t h e e arl y 
t er mi n ati o n visit) m ust b e r ec or d e d o n t h e A E C R F wit h t h e st at us of t h e A E n ot e d.  
 
A d v ers e e v e nt r e p orti n g b e gi ns fr o m t h e si g ni n g of i nf or m e d c o ns e nt. A d v ers e e v e nts s h o ul d b e 
f oll o w e d u ntil r es ol v e d or 3 0 d a ys aft er t h e fi n al st u d y tr e at m e nt.  I n a n y c as e, s eri o us a d v ers e e v e nts 
t h at ar e n ot r es ol v e d or c o nsi d er e d t o b e c hr o nic wit hi n 3 0 d a ys of t h e fi n al st u d y tr e at m e nt m ust b e 
f oll o w e d b y t h e i n v esti g at or u ntil t h e y b ec o m e r es ol v e d or ar e c o nsi d er e d t o b e c hr o nic (st a biliz e d f or 
at l e ast 3 0 d a ys).  All e v e nts t h at ar e o n g oi n g at t his ti m e will b e r ec or d e d as o n g oi n g o n t h e C R F.  
 
7. 3. 1 E x p e dit e d R e p orti n g R es p o nsi biliti es of t h e St u d y C e nt er  
F or a n y s eri o us or u n ex p ect e d a d v ers e e v e nt, t h e s p o ns or m ust b e n otifi e d wit hi n 2 4 h o urs  of w h e n 
t h e I n v esti g at or first l e ar ns of t h e occ urr e nc e of t h e e v e nt. Ex p e dit e d r e p orti n g r e q uir e m e nts f or 
s eri o us a d v ers e e v e nts ar e d escri b e d b el o w. A d e q u at e i nf or m ati o n m ust b e c oll ect e d wit h s u p p orti n g 
d oc u m e nt ati o n t o c o m pl et e a st a n d ar d r e p ort f or s u b missi o n t o P erri g o. T h e a d v ers e e v e nt t er m o n 
t h e A E C R F a n d t h e S A E r e p ort s h o ul d a gr e e ex actl y. S p eci al att e nti o n s h o ul d b e gi v e n t o r ec or di n g 
h os pit aliz ati o ns a n d c o nc o mit a nt m e dic ati o ns.   
 
S u bj ects wit h u nr es ol v e d a d v ers e e v e nt(s) or s eri o us a d v ers e  e v e nt(s) s h o ul d b e f oll o w e d b y t h e 
i n v esti g at or u ntil t h e e v e nts ar e r es ol v e d, e v e nt(s) d et er mi n e d t o b e c hr o nic or t h e s u bj ect is l ost t o 
f oll o w-u p.   R es ol uti o n  m e a ns  t h e  s u bj ect  h as  r et ur n e d  t o  t h e  b as eli n e  st at e  of  h e alt h,  or  t h e  
i n v esti g at or d o es n ot ex p ect  a n y  f urt h er i m pr o v e m e nt  or w ors e ni n g  of  t h e a d v ers e  e v e nt. T h e 
i n v esti g at or s h o ul d c o nti n u e t o r e p ort a n y si g nific a nt f oll ow- u p i nf or m ati o n t o t h e s p o ns or u p t o t h e 
p oi nt  t h at  t h e  e v e nt  h as  r es ol v e d.   A n y  s eri o us  a d v ers e  e v e nt  r e p ort e d  b y  t h e  s u bj ec t  t o  t h e  
i n v esti g at or  t h at  occ urs  wit hi n  3 0  d a ys  aft er  t h e  l ast  ass ess m e nt,  a n d  ar e  d et er mi n e d  b y  t h e  
i n v esti g at or t o b e r e as o n a bl y ass oci at e d wit h t h e us e of t h e st u d y m e dic ati o n, s h o ul d b e r e p ort e d t o 
t h e s p o ns or wit hi n 2 4 h o urs of w h e n t h e I n v esti g at or first l e ar ns of t h e occ urr e nc e of t h e e v e nt.   
 
W h e n r e p orti n g a s eri o us a d v ers e e v e nt ( S A E) t h e I n v esti g at or ( or t h e St u d y C o or di n at or) will pr o m ptl y 
r e p ort a n y s eri o us a d v ers e e v e nt or pr e g n a ncy b y t el e p h o n e t o 
 i m m e di at el y aft er t h e i n v esti g at or b ec o m es a w ar e of t h e 
e v e nt.  A n S A E f or m s h o ul d b e c o m pl et e d a n d s e nt b y f ax, e m ail, or o v er ni g ht c o uri er t o  
 wit hi n 
2 4 h o urs of k n o wl e d g e of t h e e v e nt b y t h e sit e.  I n m a n y c as es, o nl y pr eli mi n ar y i nf or m ati o n will b e 
a v ail a bl e.  A p pr o pri at e  f oll o w  u p  i nf or m ati o n  s h o ul d  b e  s o u g ht  ( h os pit al  disc h ar g e  s u m m ari es,  
o p er ati v e r e p orts , etc.) a n d a f oll o w u p S A E r e p ort f or m s u b mitt e d.  A d esi g n ati o n of c a us alit y fr o m 
t h e st u d y m e dic ati o n s h o ul d al w a ys b e i ncl u d e d wit h a f oll o w u p r e p ort.  Ass ess a n d r e p ort t h e 
c a us alit y of t h e e v e nt. 
 
7. 3. 2 S u b mitti n g a n E x p e dit e d S af et y R e p ort t o t h e I R B  

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 5  of 5 3  
 
O nc e  
 r ec ei v es all s u p p orti n g d oc u m e nt ati o n f or t h e r e p ort e d e v e nt, t h e M e dic al M o nit or, i n 
c o nj u ncti o n wit h P erri g o, will d et er mi n e if t h e s af et y r e p ort is eli gi bl e f or ex p e dit e d r e vi e w.  
 
will l o g t h e i niti al e v e nt a n d will n otif y t h e s p o ns or t h at a n e v e nt h as b e e n r e p ort e d wit hi n 1 b usi n ess 
d a y aft er i niti al r ec ei pt.  
 will c o m pl et e t h e r e vi e w of t h e e v e nt, e nt er i nf or m ati o n i nt o t h eir 
s af et y d at a b as e a n d g e n er at e t h e r e p ort. T his f or m, as w ell as ot h er s u p p orti n g d oc u m e nt ati o n, will 
b e f or w ar d e d t o  
 M e dic al M o nit or f or r evi e w.   
 will fi n aliz e t h e r e p ort a n d distri b ut e it 
t o t h e s p o ns or wit hi n 1 ( o n e)  d a y aft er i niti al r ec ei pt. W h e n ex p e dit e d s af et y r e p orti n g t o r e g ul at or y 
a ut h oriti es is i n d e e d r e q uir e d, t h e I n v esti g at or s h o ul d r e vi e w a n d u p d at e a n y n e wl y a v ail a bl e m at eri als 
at o nc e.  F oll o w -u p q u eri es m a y b e s e nt t o t h e st u d y c e nt er t o f urt h er cl arif y t h e e v e nt.  
 
E ac h ex p e dit e d s af et y r e p ort will r o uti n el y i ncl u d e a bri ef c o v er m e m or a n d u m, t h e c o m pl et e d r e p ort, 
a n d a n y a d diti o n al p erti n e nt i nf or m ati o n r ec o m m e n d e d b y  
, P erri g o, or st u d y M e dic al M o nit or. 
O nc e t h e r e p ort is ass e m bl e d, t h e Pri nci p al I n v esti g at or m ust s u b mit t h e ex p e dit e d s af et y r e p ort t o 
t h e  I R B  wit hi n  t h e  r e q uir e d  r e p orti n g  ti m efr a m e.  F oll o w-u p  r e p orts  s h o ul d  b e  s u b mitt e d  w h e n 
r e q u est e d or w h e n p erti n e nt i nf or m ati o n b ec o m es a v ail a bl e.  
 
W h e n a Pri nci p al I n v esti g at or r ec ei v es a n ex p e dit e d s af et y r e p ort fr o m  
 or t h e s p o ns or d et aili n g 
a d v ers e e v e nts occ urri n g at ot h er st u d y c e nt ers u n d er t his pr ot oc ol, it m ust b e pr o m ptl y s u b mitt e d t o 
t h e st u d y c e nt er’s I R B.  T h e Pri nci p al I n v esti g at or m ust r et ai n a c o p y of s uc h r e p orts as s u b mitt e d t o 
t h eir I R B i n t h e sit e’s st u d y R e g ul at or y Bi n d er. 
 
7. 4 S A E & A Es R e q uiri n g Disc o nti n u ati o n of St u d y Dr u g, i ncl u di n g Pr e g n a nci es  
A N Y S A E, W HI C H O C C U R S A F T E R A S U BJ E C T H A S E N T E R E D T H E S T U D Y, W H E T H E R O R N O T R EL A T E D T O 
S T U D Y M E DI C A TI O N,  M U S T  B E  R E P O R T E D  T O  
 A N D  P E R RI G O  I M M E DI A T EL Y  ( WI T HI N  2 4  
H O U R S) VI A  T EL E P H O N E  O R F A C SI MIL E. I F  I NI TI ALL Y  R E P O R T E D  VI A  T EL E P H O N E,  T HI S  M U S T  B E 
F OLL O W E D- U P B Y A F A C SI MIL E O F T H E W RI T T E N S A E R E P O R T WI T HI N 2 4 H O U R S O F T H E C ALL T O 
. 
 
N o n -s eri o us  e v e nts t h at  r e q uir e  disc o nti n u ati o n  of  st u d y  m e dic ati o n  (i ncl u di n g  l a b or at or y  
a b n or m aliti es) s h o ul d b e r e p ort e d t o P erri g o i m m e di at el y a n d wit hi n 1 w or ki n g d a y.  
 
S u bj ects w h o disc o nti n u e d u e t o ex p eri e nci n g a dv ers e e v e nts s h o ul d b e f oll o w e d cli nic a ll y u ntil t h eir 
h e alt h h as r et ur n e d t o b as eli n e st at us, or u ntil all p ar a m et ers h a v e r et ur n e d t o n or m al.  It is ex p ect e d 
t h at t h e i n v esti g at or will pr o vi d e or arr a n g e a p pr o pri at e s u p p orti v e c ar e f or t h e s u bj ect. 
 
A s u bj ect w h o ex p eri e nc es a s e v er e a d v ers e e v e nt r el at e d t o st u d y dr u g will b e disc o nti n u e d fr o m t h e 
st u d y. 
 
T h e n otific ati o n a b o ut a n y s eri o us a d v ers e e v e nt s h o ul d b e dir ect e d t o:  
 
 
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 6  of 5 3  
 
 
                                        
 
 
 
 
 
 
 
 
 
 
7. 4. 1 Pr e g n a nc y  
At t h e ti m e a Pri nci p al I nv esti g at or or sit e p ers o n n el b ec o m es a w ar e t h at a st u d y p artici p a nt b ec a m e 
pr e g n a nt f oll o wi n g st u d y p artici p ati o n, t h e Pri nci p al I n v esti g at or or d esi g n e e will r e p ort t h e pr e g n a ncy 
i m m e di at el y b y p h o n e a n d/ or b y f axi n g a c o m pl et e d Pr e g n a ncy R e p ort t o  
 wit hi n o n e w or ki n g 
d a y of b ei n g n otifi e d of t h e pr e g n a ncy r e p ort.  
 
T h e r e p ort  will i ncl u d e t h e f oll o wi n g el e m e nts: 
•  P artici p a nt ( m ot h er’s) c o d e d st u d y i d e ntifi er;  
•  D at e of p artici p a nt’s l ast m e nstr u al p eri o d;  
•  T ot al acc u m ul at e d d os e of st u d y tr e at m e nt a d mi nist er e d t o d at e;  
•  D at e of st u d y m e dic ati o n a d mi nistr ati o n.  
 
T h e i n v esti g at or will f oll o w t h e s u bj ect u ntil c o m pl eti o n of t h e pr e g n a ncy a n d m ust ass ess t h e o utc o m e 
i n t h e s h ort est p ossi bl e ti m e b ut n ot m or e t h a n 3 0 d a ys wit hi n c o m pl eti o n of t h e pr e g n a ncy. 
 
U p o n d eli v er y, misc arri a g e or a b orti o n, t h e Pri nci p al I n v esti g at or or d esi g n e e m ust f or w ar d a  f oll o w-
u p Pr e g n a ncy R e p ort wit h a n y r el e v a nt i nf or m ati o n o n t h e pr es e nt c o n diti o n of t h e f et us t o t h e 
S y m bi o, i ncl u di n g:  
•  M ot h er’s c o d e d st u d y i d e ntifi er(s);  
•  G est ati o n al a g e at d eli v er y, misc arri a g e or a b orti o n;  
•  Birt h w ei g ht, g e n d er, l e n gt h a n d h e a d circ u m f er e nc e, if a v ail a bl e; 
•  A p g ar sc or es r ec or d e d aft er birt h, if a v ail a bl e;  
•  A n y a b n or m aliti es.  
 
If t h e o utc o m e of t h e pr e g n a ncy m e ets t h e crit eri a f or i m m e di at e cl assific ati o n of a n S A E  ( e. g., 
s p o nt a n e o us or t h er a p e utic a b orti o n [ a n y c o n g e nit al a n o m al y d et ect e d i n a n a b ort e d f et us is t o b e 
d oc u m e nt e d], still birt h, n e o n at al d e at h, or c o n g e nit al a n o m al y), t h e i n v esti g at or will r e p ort t h e e v e nt 
b y p h o n e a n d b y f axi n g a c o m pl et e d S A E r e p ort f or m t o  
 wit hi n o n e w or ki n g d a y of b ei n g 
n otifi e d of t h e pr e g n a ncy r e p ort.  
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 7  of 5 3  
 
If t h e tri al is c o m pl et e d b ef or e t h e o utc o m e of t h e pr e g n a ncy is k n o w n,  
 will ass u m e t h e 
r es p o nsi bilit y f or f oll o wi n g u p o n t h e pr e g n a ncy.    
 will c o nt act t h e I n vesti g at or or St u d y 
c o or di n at or o n or ar o u n d t h e p ot e nti al ex p ect e d d at e of d eli v er y t o f oll o w -u p o n t h e o utc o m e of 
pr e g n a ncy a n d will als o c h ec k o n t h e st at us of t h e i nf a nt 8 w e e ks p ost -d eliv er y.  U p o n a w ar e n ess of 
t h e pr e g n a ncy o utc o m e a n d k n o w n st at us of t h e i nf a nt f oll o wi n g 8 w e e ks of d eli v er y, t h e 
i n v esti g at or will c o m pl et e t h e a p plic a bl e pr e g n a ncy r e p ort f or ms a n d f ax t o  
 wit hi n 1 d a y of 
b ei n g n otifi e d.  
 
7. 5 P ost St u d y A d v ers e E v e nts  
 
7. 5. 1 N o n -s eri o us A d v ers e E v e nts 
A d v ers e e v e nts t h at ar e i d e nt ifi e d at t h e l ast ass ess m e nt visit ( or t h e e arl y t er mi n ati o n visit) m ust b e 
r ec or d e d o n t h e A E C R F wit h t h e st at us of t h e A E n ot e d.   
 
7. 5. 2 S eri o us A d v ers e E v e nts  
S eri o us a d v ers e e v e nts t h at ar e i d e ntifi e d o n t h e l ast ass ess m e nt visit ( or t h e e arl y t er mi n ati o n visit) 
m ust b e r ec or d e d o n t h e A E C R F p a g e a n d r e p ort e d t o P erri g o acc or di n g t o t h e pr oc e d ur es o utli n e d 
a b o v e. S u bj ects wit h u nr es ol v e d pr e vi o usl y r e p ort e d s e ri o us a d v ers e ev e nts, or a n y n e w s eri o us 
a d v ers e e v e nts i d e ntifi e d o n t h e l ast ass ess m e nt visit, s h o ul d b e f oll o w e d b y t h e i n v esti g at or u ntil t h e 
e v e nts ar e r es ol v e d, or t h e s u bj ect is l ost t o f oll o w -u p.  R es ol uti o n m e a ns t h e s u bj ect h as r et ur n e d t o 
t h e b as eli n e st at e of h e alt h, or t h e i n v esti g at or d o es n ot ex p ect a n y f urt h er i m pr o v e m e nt or w ors e ni n g 
of t h e a d v ers e e v e nt.  T h e i n v esti g at or s h o ul d c o nti n u e t o r e p ort a n y si g nific a nt f oll o w -u p i nf or m ati o n 
t o P erri g o u p t o t h e p oi nt t h at t h e e v e nt h as r es ol v e d.  A n y s eri o us a d v ers e e v e nt r e p ort e d b y t h e 
s u bj ect  t o  t h e  i n v esti g at or t h at  occ urs  aft er  t h e  l ast  ass ess m e nt,  a n d  ar e  d et er mi n e d  b y  t h e  
i n v esti g at or t o b e r e as o n a bl y ass oci at e d wit h t h e us e of t h e st u d y dr u g, s h o ul d b e r e p ort e d t o P erri g o. 
 
8. S T A TI S TI C AL  A N AL Y SI S  
T h e s ecti o ns t h at f oll o w hi g hli g ht s a m pl e siz e d et er mi n ati o n a n d t h e pl a n n e d a n al ys es f or t his st u d y.  
A st atistic al a n al ysis pl a n ( S A P) will b e pr e p ar e d s e p ar at el y fr o m t his pr ot oc ol w hic h gi v es 
d escri pti o ns of t h e st atistic al m et h o ds, m o d els, hy p ot h es es a n d s u bj ect p o p ul ati o ns t o b e a n al yz e d.  
T h e S A P will b e c o m pl et e d a n d a p pr o v e d b ef or e l oc ki n g t h e d at a b as e a n d u n bli n di n g t h e st u d y a n d 
will s er v e as a c o m p a ni o n t o t h e pr ot oc ol a n d t h e d e f act o  d oc u m e nt ati o n of t h e pr o p os e d st atistic al 
e v al u ati o n.  T h e S A P will b e c o m pl et e d a n d fi n aliz e d pri or t o br e a ki n g t h e bli n d.  
 
8. 1 St atistic al A n al ysis Pl a n  
 
8. 1. 1 A n al ysis P o p ul ati o ns  
T h e f oll o wi n g p o p ul ati o ns ar e d efi n e d f or t h e p ur p os e of a n al ys es:  
•  I nt e nt-t o-Tr e at (I T T) (s af et y p o p ul ati o n):  A n y s u bj ect t h at w as r a n d o miz e d, r ec ei v e d a n d us e d 
st u d y m e dic ati o n. 
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 8  of 5 3  
 
•  M o difi e d I nt e nt -t o-Tr e at ( mI T T):  A n y s u bj ect, w h o m et t h e i ncl usi o n/ excl usi o n crit eri a, w as 
r a n d o miz e d, r ec ei v e d a n d us e d t h e st u d y m e dic ati o n, a n d r et ur n e d f or at l e ast o n e p ost -
b as eli n e effic acy ass ess m e nt.  
 
•  P er Pr ot oc ol ( P P) :  A n y s u bj ect: 
•  W h o m et i ncl usi o n/ excl usi o n crit eri a,  
•  W h o w as r a n d o miz e d a n d r ec ei v e d a n d us e d st u dy m e dic ati o n,  
•  W h o m et t h e pr ot oc ol crit eri a f or c o m pli a nc e 
  
 
a n d  
•  W h o c o m pl et e d Visit 4/ W e e k 1 2/ D a y 8 4 ( E n d of Tr e at m e nt/ E arl y T er mi n ati o n Visit) wit hi n 
wi n d o w O R w as disc o nti n u e d  fr o m t h e st u d y d u e t o tr e at m e nt f ail ur e. 
•  Wit h o ut si g nific a nt pr ot oc ol vi ol ati o ns t h at c o ul d h a v e i nt erf er e d wit h t h e a d mi nistr ati o n 
of t h e tr e at m e nt or t h e pr ecis e e v al u ati o n of tr e at m e nt effic acy.  
 
 
 
 
 
 
 
 
 
 
 
. 
 
8. 1. 2 Pl a n n e d A n al ysis  
All r a n d o miz e d s u bj ects w h o r ec ei v e d / us e d st u d y m e dic ati o n will b e e v al u at e d f or s af et y. T h e effic acy 
a n al ysis will b e c o n d uct e d o n b ot h t h e P P a n d t h e mI T T s u bj ect p o p ul ati o ns.  T w o -si d e d h y p ot h esis 
t esti n g will b e c o n d uct e d.  R es ulti n g p - val u es l ess t h a n 0. 0 5 will b e c o nsi d er e d st atistic all y si g nific a nt.  
N o a dj ust m e nts of p -v al u es f or m ulti pl e c o m p aris o ns will b e m a d e.  N o i nt eri m a n al ys es ar e pl a n n e d.  
S A S s oft w ar e will b e us e d f or all d at a a n al ys es a n d t a b ul ati o ns.  
 
T h e tr e at m e nt r es p o ns e will b e s u m m ariz e d b y tr e at m e nt gr o u p f or t h e e n d -of -tr e at m e nt e v al u ati o n.  
 
T h e pri m ar y effic acy e n d p oi nt will b e t h e m e a n p erc e nt c h a n g e fr o m b as eli n e t o Visit 4/ W e e k 1 2 ( D a y 
8 4) i n t h e i nfl a m m at or y ( p a p ul es a n d p ust ul es) l esi o n c o u nt.  
 
T h e s ec o n d ar y e n d p oi nt will b e t h e pr o p orti o n of s u bj ects wit h cli nic al s ucc ess d efi n e d as a sc or e of 
cl e ar or al m ost cl e ar (sc or e of 0 or 1) o n t h e I n v esti g at or Gl o b al Ass ess m e nt (I G A) at Visit 4/ W e ek 1 2  
( D a y 8 4). 
 
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 3 9  of 5 3  
 
 
8. 1. 3 S a m pl e Siz e C o nsi d er ati o ns  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 
 
8. 1. 4 Ef fic ac y M e as ur es a n d A n al ysis 
 
Cli nic al e n d p oi nts  
T h e pri m ar y effic acy m e as ur e will b e t h e m e a n p erc e nt c h a n g e fr o m b as eli n e t o Visit 4/ W e e k 1 2  ( D a y 
8 4)  i n t h e i nfl a m m at or y ( p a p ul es a n d p ust ul es) l esi o n c o u nts. T h e s ec o n d ar y effic acy m e as ur e will b e 
t h e pr o p orti o n of s u bj ects wit h cli nic al s ucc ess d efi n e d as a sc or e of cl e ar or al m ost cl e ar (sc or e of 0 
or 1) o n t h e I n v esti g at or Gl o b al Ass ess m e nt (I G A) at Visit 4/ W e e k 1 2  ( D a y 8 4). 
 
E q ui v al e nt effic acy  
F or t h e m e a n p erc e nt c h a n g e fr o m b as eli n e i n t h e i nfl a m m at or y l esi o n c o u nt, t h e T est tr e at m e nt will 
b e c o nsi d er e d t o b e t h er a p e utic all y e q ui v al e nt t o t h e R ef er e nc e tr e at m e nt if t h e 9 0 % c o nfi d e nc e 
i nt er v al o n t h e T est-t o-R ef er e nc e r ati o of m e a ns, c alc ul at e d b y Fi ell er’s M et h o d, f alls wit hi n t h e 
i nt er v al 0. 8 0 t o 1. 2 5. T h e tr e at m e nt m e a ns a n d esti m at e of r esi d u al v ari a nc e f or t h e c o nfi d e nc e 
i nt er v al c alc ul ati o n will c o m e fr o m a n A n al ysis of V ari a nc e of t h e T est a n d R ef er e nc e r es ults usi n g a 
st atistic al m o d el c o nt ai ni n g t er ms f or Tr e at m e nt a n d Sit e . 
 
F or t h e pr o p orti o n of s u bj ects wit h cli nic al s ucc ess, t h e T est tr e at m e nt will b e c o nsi d er e d t o b e 
t h er a p e utic all y e q ui v al e nt t o t h e R ef er e nc e tr e at m e nt if t h e 9 0 % c o nfi d e nc e i nt er v al o n t h e diff er e nc e 
b et w e e n T est a n d t h e R ef er e nc e pr o p orti o ns  is c o nt ai n e d wit hi n t h e i nt er v al – 2 0 % t o + 2 0 %. T h e 
c o nfi d e nc e i nt er v al will b e c o nstr uct e d usi n g W al d’s m et h o d wit h Y at es’ c o nti n uit y c orr ecti o n.  
 
T h er a p e utic e q ui v al e nc e e v al u ati o ns i n t h e p er -pr ot oc ol ( P P) p o p ul ati o n will b e c o nsi d er e d d efi niti v e 
a n d t h os e i n t h e mI T T will b e c o nsi d er e d s u p p ortiv e.  

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 4 0  of 5 3  
 
 
S u p eri orit y  
F or t h e m e a n p erc e nt c h a n g e fr o m b as eli n e i n t h e i nfl a m m at or y l esi o n c o u nt, e ac h acti v e tr e at m e nt 
will b e e v al u at e d t o d et er mi n e if it h as s u p eri or effic acy t o t h at of t h e V e hicl e at Visit 4/ W e e k 1 2 ( D a y 
8 4)  vi a a n A n al ysis of V ari a nc e usi n g Pr oc Mix e d of S A S wit h Tr e at m e nt a n d Sit e  as f act ors .  
 
T h e pr o p orti o n of s u bj ects wit h cli nic al s ucc ess f or e ac h acti v e tr e at m e nt will b e c o m p ar e d t o t h at of 
t h e V e hicl e usi n g Z- t est wit h Y at e’s c o nti n uit y c orr ecti o n. 
 
S u p eri orit y t ests will b e t w o -si d e d at a si g nific a nc e l e v el of α = 0. 0 5. S u p eri orit y a n al ys es i n t h e mI T T 
p o p ul ati o n will b e c o nsi d er e d d efi niti v e a n d t h os e i n t h e P P will b e c o nsi d er e d s u p p orti v e  
 
8. 1. 5 S af et y a n d A d v ers e E v e nts A n al ysis  
T h e fr e q u e ncy a n d p erc e nt of s u bj ects wit h a d v ers e e v e nts will b e s u m m ariz e d b y M e d D R A s yst e m 
or g a n cl ass a n d pr ef err e d t er m a n d b y s e v erit y a n d r el ati o ns hi p t o st u d y dr u g f or all t hr e e tr e at m e nt 
gr o u ps. 
 
T h e c o m p ar a bl e s af et y of t h e T est a n d R ef er e nc e tr e at m e nts will b e e v al u at e d 
b y st atistic al c o m p aris o n of t h e pr o p orti o n of s u bj ects w h o r e p ort e d a n y a d v ers e e v e nts.  S af ety 
c o m p aris o ns will b e p erf or m e d o nl y f or t h e s af ety i nt e nt -t o-tr e at p o p ul ati o n. 
 
8. 2 C o m p ar a bilit y of S u bj ects at B as eli n e  
D escri pti v e st atistics will b e pr es e nt e d, b y tr e at m e nt gr o u p, f or s u bj ect b as eli n e c h ar act eristics. T h e 
si g nific a nc e of a n y o b vi o us tr e at m e nt gr o u p diff er e nc es will b e disc uss e d i n t h e C S R. 
 
9.  C O N S E N T C O N SI D E R A TI O N S A N D P R O C E D U R E S  
It will b e m a d e cl e ar t o t h e s u bj ect t h at, f or t h e p ur p os es of t h e st u d y, t h e y ar e c o ns e nti n g o nl y f or 
t o pic al a p plic ati o n of m e dic ati o n or v e hicl e.  I n v esti g at ors m a y disc uss t h e a v ail a bilit y of t h e st u d y a n d 
t h e p ossi bilit y f or e ntr y wit h a p ot e nti al s u bj ect wit h o ut first o bt ai ni n g c o ns e nt. H o w e v er, i nf or m e d 
c o ns e nt m ust b e o bt ai n e d a n d d oc u m e nt e d pri or t o i niti ati o n of a n y pr oc e d ur es t h at ar e p erf or m e d 
s ol el y f or t h e p ur p os e of  d et er mi ni n g eli gi bility f or r es e arc h, i ncl u di n g wit h dr a w al fr o m c urr e nt 
m e dic ati o n(s).  W h e n t his is d o n e i n a ntici p ati o n of, or i n pr e p ar ati o n f or, t h e r es e arc h, it is c o nsi d er e d 
t o b e p art of t h e r es e arc h. 
 
T h e st u d y m ust b e a p pr ov e d i n writi n g b y a n a p pr o pri at e I R B as d efi n e d b y F D A r e g ul ati o ns.  A c o p y of 
t h e L ett er of A p pr o v al fr o m t h e I R B, w hic h als o c o nt ai ns s p ecific i d e ntific ati o n of t h e d oc u m e nts 
a p pr o v e d, m ust b e r ec eiv e d b y P erri g o, pri or t o st u d y c o m m e nc e m e nt.  
 
P eri o dic st at us r e p orts m ust b e s u b mitt e d t o t h e I R B at l e ast a n n u all y as r e q uir e d b y t h e sit e’s I R B, as 
w ell a s n otific ati o n of c o m pl eti o n of t h e st u d y a n d a fi n al r e p ort wit hi n t hr e e m o nt hs of st u d y 
c o m pl eti o n or t er mi n ati o n.  A c o p y of all r e p orts s u b mitt e d t o t h e I R B m ust b e s e nt t o P erri g o.  
 
T h e  i n v esti g at or(s)  h as  b ot h  et hic al  a n d  l e g al  r es p o nsi bilit y  t o  e ns u r e  t h at  e ac h  s u bj ect  b ei n g  
c o nsi d er e d  f or i ncl usi o n i n t his  st u d y is  gi v e n a  f ull  ex pl a n ati o n  of  t h e  pr ot oc ol.  T his  s h all  b e 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 4 1  of 5 3  
 
d oc u m e nt e d o n a writt e n i nf or m e d c o ns e nt f or m, w hic h s h all b e a p pr ov e d b y t h e s a m e I nstit uti o n al 
R e vi e w B o ar d (I R B) r es p o nsi bl e f o r a p pr o v al of t his pr ot oc ol. E ac h i nf or m e d c o ns e nt f or m s h all i ncl u d e 
t h e el e m e nts r e q uir e d b y F D A r e g ul ati o ns i n 2 1 C F R P art 5 0.  T h e i n v esti g at or a gr e es t o o bt ai n a p pr ov al 
fr o m P erri g o of a n y writt e n i nf or m e d c o ns e nt f or m us e d i n t h e st u d y, pr ef er a bl y pri or t o s u b missi o n 
t o t h e I R B. 
 
O nc e t h e a p pr o pri at e ess e nti al i nf or m ati o n h as b e e n pr o vi d e d t o t h e s u bj ect a n d f ull y ex pl ai n e d by 
t h e i n v esti g at ors ( or a q u alifi e d d esi g n e e) a n d it is f elt t h at t h e s u bj ect u n d erst a n ds t h e i m plic ati o ns of 
p artici p ati n g, t h e  I R B-a p pr o v e d writt e n i nf or m e d c o ns e nt f or m s h all b e si g n e d b y t h e s u bj ect ( or t h eir 
p ar e nt/l e g all y a ut h oriz e d r e pr es e nt ati v e) a n d t h e p ers o n o bt ai ni n g c o ns e nt (i n v esti g at or or d esi g n e e).  
T h e s u bj ect s h all b e gi v e n a c o p y of t h e si g n e d i nf or m e d c o ns e nt f or m a n d t h e i n v esti g at or s h all k e e p 
t h e ori gi n al o n fil e. 
 
If t h e s u bj ect f ails t o m e et t h e i ncl usi o n/ excl usi o n crit eri a at t h e c o ncl usi o n of t h e scr e e ni n g p h as e, t h e 
s u bj ect will b e wit h dr a w n fr o m scr e e ni n g.  I n t h e e v e nt t h at t h e s u bj ect is r e -scr e e n e d f or st u d y 
p artici p ati o n, a n e w i nf or m e d c o ns e nt f or m m ust b e si g n e d.  
 
9. 1 S u bj ect C o nfi d e nti alit y  
All p artici p a nts ar e c o nc er n e d f or t h e i n di vi d u al s u bj ect’s pri v acy a n d, t h er ef or e, all s u bj ect d at a will 
b e i d e ntifi e d o nl y b y a s u bj ect i d e ntific ati o n n u m b er a n d s u bj ect i niti als. H o w e v er, i n c o m pli a nc e wit h 
f e d er al g ui d eli n es r e g ar di n g t h e m o nit ori n g of cli nic al st u di es a n d i n f ulfill m e nt of his/ h er o bli g ati o ns 
t o P erri g o, it is r e q uir e d t h at t h e i n v esti g at or p er mit t h e st u d y m o nit or, a n y P erri g o a ut h oriz e d 
r epr es e nt ati v e, a n d/ or F D A r e pr es e nt ati v e t o r e vi e w t h at p orti o n of t h e s u bj ect’s m e dic al r ec or d t h at 
is dir ectl y r el at e d t o t h e st u d y.  T his s h all i ncl u d e all st u d y r el e v a nt d oc u m e nt ati o n i ncl u di n g s u bj ect 
m e dic al hist ori es t o v erif y eli gi bilit y, l a b or at or y  t est r es ult r e p orts t o v erif y tr a nscri pti o n acc ur acy, 
a d missi o n/ disc h ar g e s u m m ari es f or h os pit al st ays occ urri n g w hil e t h e s u bj ect is e nr oll e d i n t h e st u d y 
a n d a ut o ps y r e p orts f or d e at hs occ urri n g d uri n g t h e st u d y.  
 
As p art of t h e r e q uir e d c o nt e nt of i nf or m e d c o ns e nt, t h e s u bj ect m ust b e i nf or m e d t h at his/ h er m e dic al 
c h art m a y b e r e vi e w e d by P erri g o or t h eir a ut h oriz e d r e pr es e nt ati v e, or a r e pr es e nt ati v e of t h e F D A.  
S h o ul d acc ess t o t h e m e dic al r ec or d r e q uir e a s e p ar at e w ai v er or a ut h oriz ati o n, it is t h e i n v esti g at or’s 
r es p o nsi bilit y t o o bt ai n s uc h p er missi o n fr o m t h e s u bj ect i n writi n g b ef or e t h e s u bj ect is e nt er e d i nt o 
t h e st u d y. 
 
T o pr es er v e t h e s u bj ect's c o nfi d e nti alit y, t h e d at a c oll ect e d will b e a v ail a bl e o nl y t o t h e i n v esti g at ors 
of t h e st u d y, t h eir  s u p p ort st aff, P erri g o or t h eir a ut h oriz e d r e pr es e nt ati v e a n d p ossi bl y t h e F D A. 
 
All r e p orts a n d c o m m u nic ati o ns r el ati n g t o t h e s u bj ect i n t h e st u d y will i d e ntif y e ac h s u bj ect o nl y b y 
t h e s u bj ect’s i niti als a n d b y t h e s u bj ect n u m b er. T h e i n v esti g at or a gr ees t o f ur nis h P erri g o wit h 
c o m pl et e s u bj ect i d e ntific ati o n, if n ec ess ar y o n a c o nfi d e nti al f oll o w -u p f or m, w hic h will b e us e d f or 
t h e p ur p os e of a l o n g-t er m f oll o w-u p, if n e e d e d.  T his will b e tr e at e d wit h strict a d h er e nc e t o 
pr of essi o n al st a n d ar ds of c o nf i d e nti alit y a n d will b e fil e d at P erri g o u n d er a d e q u at e s ec urit y a n d 
r estrict e d acc essi bilit y. 
 

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P a g e 4 2  of 5 3  
 
9.  
C O N D U C T O F S T U D Y  
T h e i n v esti g ati o n al sit e is t o m ai nt ai n c o m pl et e d oc u m e nt ati o n of all e v e nts a n d t h e ti m es at w hic h 
t h e y occ ur. 
 
1 0. 1 C o m pl eti o n of St u d y  
T h e  i n v esti g ati o n al  sit e  will  c o m pl et e  t h e  st u d y  a n d  c o m pl et e  all  d oc u m e nt ati o n  r e q uir e d,  i n  
s atisf act or y c o m pli a nc e wit h t h e pr ot oc ol, wit hi n 3. 5 m o nt hs of e nr oll m e nt of t h e l ast s u bj ect a n d 
ext e n di n g b e y o n d as n e e d e d t o c o m pl et e n ec ess ar y d at a q u eri es.  
 
It is a gr e e d t h at, f or r e as o n a bl e c a us e, eit h er t h e i n v esti g at or or P erri g o m a y t er mi n at e t his st u d y 
b ef or e c o m pl eti o n pr o vi d e d writt e n n otic e is s u b mitt e d at a r e as o n a bl e ti m e i n a d v a nc e of i nt e n d e d 
t er mi n ati o n.  A n y ext e nsi o n of t his st u d y m ust b e m ut u all y a gr e e d u p o n i n writi n g b y b ot h t h e 
i n v esti g at or a n d P erri g o. 
 
1 0. 2 Pr ot oc ol A m e n d m e nts  
T h e I n v esti g at or will n ot m a k e a n y c h a n g es t o t his pr ot oc ol wit h o ut pri or writt e n c o ns e nt fr o m P erri g o 
a n d s u bs e q u e nt a p pr o v al b y t h e I R B.  A n y p er m a n e nt c h a n g e t o t h e pr ot oc ol, w h et h er it is a n o v er all 
c h a n g e or a c h a n g e f or s p ecific st u d y c e nt er(s), m ust b e h a n dl e d as a pr ot oc ol a m e n d m e nt. A n y 
a m e n d m e nt t o t h e pr ot oc ol t h at a p p e ars i n dic at e d as t h e st u d y pr o gr ess es will b e f ull y disc uss e d 
b et w e e n  
 a n d P erri g o. If a gr e e m e nt is r e ac h e d r e g ar di n g t h e n e e d f or a n a m e n d m e nt, t h e 
a m e n d m e nt will b e writt e n b y P erri g o. T h e writt e n a m e n d m e nt m ust b e s u b mitt e d t o t h e c h air m a n of 
t h e I R B i d e ntifi e d wit h t his r es p o nsi bilit y.  Exc e pt f or ‘ a d mi nistr ati v e a m e n d m e nts,’ i n v esti g at ors m ust 
a w ait  I R B  a p pr o v al  of  pr ot oc ol  a m e n d m e nts b ef or e  i m pl e m e nti n g  t h e  c h a n g e(s).  A d mi nistr ati v e 
a m e n d m e nts ar e d efi n e d t o h a v e n o eff ect o n t h e s af et y of t h e r es e arc h s u bj ects, sc o p e of t h e 
i n v esti g ati o n, or q u alit y of t h e tri al.  H o w e v er, a pr ot oc ol c h a n g e i nt e n d e d t o eli mi n at e a n a p p ar e nt 
i m m e di at e h az ar d t o s u bj ects s h o ul d b e i m pl e m e nt e d i m m e di at el y, a n d t h e I R B n otifi e d wit hi n fiv e 
d a ys.  P erri g o will s u b mit pr ot oc ol a m e n d m e nts t o t h e F D A or ot h er r e g ul at or y a g e nci es.  
 
W h e n, i n t h e j u d g m e nt of t h e r e vi e wi n g I R B, t h e i n v esti g at ors a n d/ or P erri g o, t h e a m e n d m e nt t o t h e 
pr ot oc ol s u bst a nti all y alt ers t h e st u d y d esi g n a n d/ or i ncr e as es t h e p ot e nti al ris k t o t h e s u bj ect, t h e 
c urr e ntl y a p pr o v e d writt e n i nf or m e d c o ns e nt f or m will r e q uir e si mil ar m o dific ati o n.  I n s uc h c as es, 
r e p e at i nf or m e d c o ns e nt will b e o bt ai n e d fr o m s u bj ects e nr oll e d i n t h e st u d y b ef or e ex p ecti n g 
c o nti n u e d p artici p ati o n. 
 
1 1. R E C O R D S M A N A G E M E N T  
 
1 1. 1 D at a C oll ecti o n  
  
C R Fs f or i n di vi d u al s u bj ects will b e pr o vi d e d 
. C R Fs m ust b e l e gi bl e a n d c o m pl et e.  C R Fs 
f or t his st u d y will b e m ai nt ai n e d i n a st u d y bi n d er a n d d at a r ec or d e d o n 2-p art N C R p a p er.  O n e c o p y 
will b e k e pt b y t h e i n v esti g at or a n d t h e ot h er c o py will  b e s u b mitt e d t o t h e C R O d at a m a n a g e m e nt 
gr o u p.  All f or ms s h o ul d b e c o m pl et e d usi n g a bl ack b all p oi nt p e n. Err ors s h o ul d b e li n e d o ut, b ut n ot 
o blit er at e d, a n d t h e c orr ecti o n i ns ert e d, i niti al e d, a n d d at e d b y d esi g n at e d st u d y p ers o n n el. F urt h er 

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P a g e 4 3  of 5 3  
 
d at a c orr ec ti o ns will b e p erf or m e d o n d at a c orr ecti o n f or ms ( D C Fs) t h at will b e pr o vi d e d b y t h e C R O 
t o t h e i n v esti g at or i n c as e of err o n e o us or u ncl e ar d at a. T h e i n v esti g at or will m a k e t h e c orr ecti o n o n 
t h e D C F a n d si g n t h e D C F. T h e si g n e d D C F will b e s u b mitt e d t o t h e C R O d at a m a n a g e m e nt gr o u p f or 
pr oc essi n g a n d a c o p y r et ai n e d wit h t h e C R Fs.  
A C R F m ust b e c o m pl et e d a n d si g n e d b y t h e i n v esti g at or f or e ac h s u bj ect e nr oll e d, i ncl u di n g t h os e 
disc o nti n u e d fr o m t h e st u d y f or a n y r e as o n. T h e r e as o n f or disc o nti n u ati o n m ust b e n ot e d o n a 
s u bj ect’s st u d y t er mi n ati o n f or m. 
C R Fs m ust b e k e pt c urr e nt t o r efl ect t h e s u bj ect’s st at us at e ac h p h as e d uri n g t h e c o urs e of t h e 
st u d y. S u bj ects ar e n ot t o b e i d e ntifi e d o n C R Fs by n a m e; a p pr o pri at el y c o d e d i d e ntific ati o n a n d t h e 
s u bj ect’s i niti als m ust b e us e d. T h e i n v esti g at or m ust k e e p a s e p ar at e l o g of t h e s u bj ect’s n a m es a n d 
a d dr ess es.  
D uri n g e ac h s u bj ect’s visit t o t h e cli nic, a d esi g n e e p artici p ati n g i n t h e st u dy will r ec or d pr o gr ess n ot es 
t o d oc u m e nt all si g nific a nt o bs er v ati o ns.  At a mi ni m u m, t h es e n ot es will c o nt ai n:  
 
a)  D oc u m e nt ati o n of t h e i nf or m e d c o ns e nt pr oc ess;  
b)  T h e d at e of t h e visit a n d t h e c orr es p o n di n g Visit or W e e k i n t h e st u d y sc h e d ul e;  
c) G e n er al  s u bj ect  st at us  r e m ar ks,  i ncl u di n g  a n y  si g nific a nt  m e dic al  fi n di n gs.   T h e  s e v erit y, 
fr e q u e ncy,  a n d  d ur ati o n  of  a n y  a d v ers e  e v e nts  a n d  t h e  i n v esti g at or's  ass ess m e nt  of  
r el ati o ns hi p t o st u d y m e dic ati o n m ust als o b e r ec or d e d. 
d)  A n y c h a n g es i n c o nc o mit a nt m e dic ati o ns or d os a g es;  
e)  A g e n er al r ef er e nc e t o t h e pr oc e d ur es c o m pl et e d; a n d  
f) T h e  si g n at ur e ( or i niti als) a n d d at e of all cli nici a ns w h o m a d e a n e ntr y i n t h e pr o gr ess n ot es. 
 
I n a d diti o n, a n y c o nt act wit h t h e s u bj ect vi a t el e p h o n e or ot h er m e a ns t h at pr o vi d es si g nific a nt cli nic al 
i nf or m ati o n will als o b e d oc u m e nt e d i n t h e pr o gr ess n ot es as d escri b e d a b o v e. 
 
A n y c h a n g es t o i nf or m ati o n i n t h e st u d y pr o gr ess n ot es a n d ot h er s o urc e d oc u m e nts, will b e e nt er e d 
i n bl ac k i n k , i niti al e d a n d d at e d b y t h e a ut h oriz e d p ers o n m a ki n g t h e c orr ecti o n/ a d diti o n.  C h a n g es 
will b e m a d e b y stri ki n g a si n gl e li n e t hr o u g h err o n e o us d at a, a n d cl e arl y e nt eri n g t h e c orr ect d at a.  
( e. g., wr o n g d at a  ri g ht d at a).  E ntri es m a y n ot b e er as e d or m as k e d wit h w hit e-o ut fl ui d.  If t h e r e as o n 
f or t h e c h a n g e is n ot a p p ar e nt, a bri ef ex pl a n ati o n f or t h e c h a n g e will b e writt e n a dj ac e nt t o t h e c h a n g e 
b y t h e cli nici a n.  
 
F or tr a ns missi o n t o P erri g o, i nf or m ati o n fr o m t h e st u d y pr o gr ess n ot es a n d ot h er s o urc e d oc u m e nts 
will b e pr o m ptl y e nt er e d i nt o t h e d at a b as e.  T h e d at a b as e als o c o nt ai ns a c o m pl et e a u dit tr ail t o 
c a pt ur e all r e g ul at or y c o m p o n e nts of d at a c orr ecti o n ( e. g., i niti al e ntr y, n e w v al u e, i niti als a n d d at e of 
t h e c h a n g e). 
 
1 1. 2 S o urc e D oc u m e nts  
S o urc e d oc u m e nts ar e d efi n e d a s t h e r es ults of  ori gi n al o bs er v ati o ns a n d  acti viti es of  a cli nic al 
i n v esti g ati o n.  S o urc e d oc u m e nts will i ncl u d e, b ut ar e n ot li mit e d t o, pr o gr ess n ot es a n d scr e e ni n g l o gs.  
All s o urc e d oc u m e nts p ert ai ni n g t o t his st u d y will b e m ai nt ai n e d b y t h e i n v esti g a t ors a n d m a d e 
a v ail a bl e f or i ns p ecti o n b y a ut h oriz e d p ers o ns.  T h e ori gi n al si g n e d i nf or m e d c o ns e nt f or m f or e ac h 

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P a g e 4 4  of 5 3  
 
p artici p ati n g s u bj ect s h all b e fil e d wit h r ec or ds k e pt b y t h e i n v esti g at ors a n d a c o p y gi v e n t o t h e 
s u bj ect. 
 
1 1. 3 Fil e M a n a g e m e nt at t h e St u d y Sit e  
It  is  t h e  r es p o nsi bilit y  of  t h e  i n v esti g at or  t o  e ns ur e  t h at  t h e  st u d y  c e nt er  fil e  is  m ai nt ai n e d  i n 
acc or d a nc e wit h S ecti o n 8 of t h e I nt er n ati o n al C o nf er e nc e o n H ar m o niz ati o n (I C H) G ui d eli n e f or G o o d 
Cli nic al Pr actic es ( G C P).  
 
1 1. 4 R ec or ds R et e nti o n at t h e St u d y Sit e  
F D A r e g ul ati o ns 2 1 C F R § 3 1 2. 5 7 r e q uir e all i n v esti g at ors p artici p ati n g i n  cli nic al dr u g st u di es t o 
m ai nt ai n d et ail e d cli nic al d at a f or o n e of t h e f oll o wi n g p eri o ds:  
 
a)  A p eri o d of at l e ast t w o y e ars f oll o wi n g t h e d at e o n w hic h a N e w Dr u g A p plic ati o n is a p pr o v e d 
b y t h e F D A;  
b)  A p eri o d of t w o y e ars aft er P erri g o  n otifi es t h e i nv esti g at or t h at n o f urt h er a p plic ati o n is t o b e 
fil e d wit h t h e F D A. 
 
T h e i n v esti g at or m ust n ot dis p os e of a n y r ec or ds r el e v a nt t o t his st u dy wit h o ut eit h er ( 1) w ritt e n 
p er missi o n fr o m P erri g o or ( 2) pr o vi di n g a n o p p ort u nit y f or P erri g o t o c oll ect s uc h r ec or ds.  T h e 
i n v esti g at or s h all t a k e r es p o nsi bilit y f or m ai nt ai ni n g a d e q u at e a n d acc ur at e el ectr o nic or h ar d c o p y 
s o urc e d oc u m e nts of all o bs er v ati o ns a n d d at a g e n er at e d d uri n g t his st u d y. S uc h d oc u m e nt ati o n is 
s u bj ect t o i ns p ecti o n b y P erri g o a n d t h e F D A. 
 
1 2.  Q U ALI T Y C O N T R OL A N D Q U ALI T Y A S S U R A N C E  
 
1 2. 1 M o nit ori n g  
P erri g o h as et hic al, l e g al a n d sci e ntific o bli g ati o ns t o c ar ef ull y f oll o w t his st u d y i n a d et ail e d a n d or d erl y 
m a n n er i n acc or d a nc e wit h est a blis h e d r es e arc h pri nci pl es a n d F D A r e g ul ati o ns.  All m e dic al r ec or ds 
(s o urc e d oc u m e nts) of t h e s u bj ects p artici p ati n g i n t his st u d y m ust b e pr es e nt e d f or r e vi e w a n d 
v erific ati o n of C R Fs.  
 
1 2. 2 A u diti n g  
P erri g o ( or r e pr es e nt ati v e) m a y c o n d uct a u dits at t h e st u d y c e nt er(s).  A u dits will i ncl u d e, b ut ar e n ot 
b e li mit e d t o, dr u g s u p pl y, pr es e nc e of r e q uir e d d oc u m e nts, t h e i nf or m e d c o ns e nt pr oc ess, a n d 
c o m p aris o n of  C R Fs  wit h s o urc e d oc u m e nts.  T h e i n v esti g at or a gr e es t o p artici p at e wit h a u dits 
c o n d uct e d at a r e as o n a bl e ti m e i n a r e as o n a bl e m a n n er.  
 
R e g ul at or y a ut h oriti es w orl d wi d e m a y als o a u dit t h e i n v esti g at or d uri n g or aft er t h e st u d y. T h e 
i n v esti g at or s h o ul d c o nt act P erri g o i m m e di at el y if n otifi e d of s uc h a n a u dit, a n d m ust f ull y c o o p er at e 
wit h t h e a u dits c o n d uct e d at a r e as o n a bl e ti m e i n a r e as o n a bl e m a n n er.  
 
1 3. E T HI C S A N D R E S P O N SI B ILI T Y 
T his st u d y m ust b e c o n d uct e d i n c o m pli a nc e wit h t h e pr ot oc ol, t h e U nit e d St at es F o o d a n d Dr u g 
A d mi nistr ati o n ( F D A) r e g ul ati o ns, a n y ot h er c o u ntri es r e g ul ati o ns, a n d I C H G C P G ui d eli n es.  

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P a g e 4 5  of 5 3  
 
 
1 4. U S E O F I N F O R M A TI O N A N D P U BLI C A TI O N  
All i nf or m ati o n s u p pli e d b y P erri g o i n c o n n ecti o n wit h t his st u d y a n d n ot pr e vi o usl y p u blis h e d, is 
c o nsi d er e d c o nfi d e nti al i nf or m ati o n.  T his i nf or m ati o n i ncl u d es, b ut is n ot li mit e d t o, d at a, m at eri als 
(i. e. t h e cli nic al pr ot oc ol, C R Fs ), e q ui p m e nt, ex p erie nc e ( w h et h er of a sci e ntific, t ec h nic al, e n gi n e eri n g, 
o p er ati o n al,  or  c o m m erci al  n at ur e),  d esi g ns,  s p ecific ati o ns,  k n o w -h o w,  pr o d uct  us es,  pr oc ess es,  
f or m ul a e, c osts, fi n a nci al d at a, m ar k eti n g pl a ns a n d dir ect s elli n g s yst e ms, c ust o m er lists a n d t ec h nic al 
a n d c o m m erci al i nf or m ati o n r el ati n g t o c ust o m ers or b usi n ess pr oj ecti o ns us e d b y P erri g o i n its 
b usi n ess. A n y d at a, i n v e nti o ns, or disc o v eri es c oll ect e d or d e v el o p e d, as a r es ult of t his st u dy is 
c o nsi d er e d c o nfi d e nti al. T his c o nfi d e nti al i nf or m ati o n s h al l r e m ai n t h e s ol e pr o p ert y of P erri g o, s h all 
n ot b e discl os e d t o a n y u n a ut h oriz e d p ers o n or us e d i n a n y u n a ut h oriz e d m a n n er wit h o ut writt e n 
c o ns e nt of P erri g o, a n d s h all n ot b e us e d exc e pt i n t h e p erf or m a nc e of t h e st u d y.  As s uc h, c o nfi d e nti al 
st u d y-r el ate d  i nf or m ati o n  s h o ul d  n ot  b e  i ncl u d e d  o n  t h e  c urric ul u m  vit a e  of  a n y  p artici p ati n g  
i n v esti g at or or st u d y st aff. 
 
T h e i nf or m ati o n d e v el o p e d d uri n g t h e c o urs e of t his cli nic al st u d y is als o c o nsi d er e d c o nfi d e nti al, a n d 
will b e us e d b y P erri g o i n c o n n ecti o n w it h t h e d e v el o p m e nt of t h e dr u g.  T h e i nf or m ati o n m a y b e 
discl os e d as d e e m e d n ec ess ar y b y P erri g o t o all o w t h e us e of t h e i nf or m ati o n d eri v e d fr o m t his cli nic al 
st u d y, t h e i n v esti g at or is o bli g e d t o pr o vi d e P erri g o wit h c o m pl et e t est r es ults a n d all d at a d e v el o p e d 
i n t h e st u d y. T h e i nf or m ati o n o bt ai n e d d uri n g t his st u d y m a y b e m a d e a v ail a bl e t o ot h er i n v esti g at ors 
w h o ar e c o n d ucti n g si mil ar st u di es.  
 
T h e i n v esti g at or s h all n ot m a k e a n y p u blic ati o n r el at e d t o t his st u d y wit h o ut t h e ex pr ess writt e n 
p er missi o n  of P erri g o.
 
 
 
 
 

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1 5. A P P E N DI C E S  
 
1 5. 1 A p p e n di x A: St u d y P ers o n n el C o nt acts  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

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1 5. 2 A P P E N DI X B:  I N S T R U C TI O N S F O R T H E S U BJ E C T 
 
C h ec k Visit Dis p e ns e d: Visit 1:  
   Visit 2:   
        Visit 3:      
    U nsc h e d ul e d visit:   
     D at e: _ _ _ _ _ _ _ _  
 
S U BJ E C T I NI TI AL S: _ _ _ _ _ _ _ _ _ _ _    S U BJ E C T N U M B E R: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ SI T E N U M B E R: _ _ _ _ _ _ _ _  
 
1.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
3.  
  
 
 
 
 
 
 
 
 
 
 
 
 
  
   
 
  
 
  
 
 

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P a g e 5 0  of 5 3  
 
9.  
 
 
 
 
 
 
 
 
 
 
1 7.  
 
  
 
 
 
 
   
 
  
  
 
  
  
 
 
  
 
 
  
   
 
 
 
 
  

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P a g e 5 1  of 5 3  
 
2 9.  
 
 
 
 
 
 
 
 
 
Y o ur c all is sc h e d ul e d f or:   _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( W e e k 2)  
  
  
  
 
          ( D at e) 
Y o u ar e sc h e d ul e d t o r et ur n at:  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( Visit 2, St u d y W e e k 4)    
( Ti m e) 
( D at e) 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( Visit 3, St u d y W e e k 8)  
( Ti m e)   
  
  
 
( D at e) 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( Visit 4, St u d y W e e k 1 2)  
( Ti m e)  
  
  
 
( D at e)  
 
ALL A P P OI N T M E N T S A R E I M P O R T A N T! I F Y O U N E E D T O R E -S C H E D UL E Y O U R A P P OI N T M E N T, PL E A S E    
C ALL Y O U R S T U D Y D O C T O R’ S O F FI C E I M M E DI A T EL Y.  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
N a m e a n d T el e p h o n e N u m b er of St u dy C o or di n at or/ St u dy Sit e  
 

Pr ot oc ol  N o: P R G -N Y - 1 6-0 0 9  
 
                                                                   
 
 
P a g e 5 3  of 5 3  
 
1 6. R E F E R E N C E S  
1.  C o h e n A. F, Ti e mstr a J. D: Dis e as e a n d Tr e at m e nt of R os ac e a . J o ur n al of A m eric a n B o ar d of 
F a mil y Pr actic e. M a y -J u n e 2 0 0 2 V ol 1 5. N o 3: 2 1 4 - 2 1 7  
2.  Z u b er TJ. R os ac e a. D er m at ol o g y. Pri m C ar e 2 0 0 0; 2 7: 3 0 9 -1 8  
3.  Kli g m a n A M. Oc ul ar R os ac e a. C urr e nt C o nc e pts a n d T h er a p y. Arc D er m at ol 1 9 9 7; 1 3 3: 8 9 -9 0.  
4.  htt ps:// w w w. a a d. or g/ d er m at ol o g y - a-t o-z/ dis e as es-a n d -tr e at m e nts 
5.  P ac k a g es i ns ert Fi n ac e a ® F o a m 1 5 % ( Az el aic Aci d, F o a m 1 5 %) d at e d J ul y 2 0 1 5 4.  
6.  w w w.fi n ac e a.c o m  
7.  O G D Dr aft G ui d a nc e o n  M etr o niz a d ol e   Cr e a m 0. 7 5 % ; M ar 2 0 1 0 a n d Az el aic Aci d G el; M a y 
2 0 1 0 a n d R e vis e d S e p 2 0 1 2  
8.  Fi n ac e a ® F o a m. htt ps:// w w w. dr u gs .c o m/ pr o/fi n ac e a-f o a m. ht ml.