A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Comparison Study to Determine the Therapeutic Equivalence of GDC 695 and Diclofenac Sodium Gel, 3% in Subjects With Actinic Keratoses
Phase: PHASE3
Conditions: Actinic Keratosis
Sponsor: Balmoral Medical company

C O N FI D E N TI A L
Pa ge 1 of 5 9 
A M U L TI C E N T E R, R A N D O MI Z E D, D O U B L E- B LI N D, P L A C E B O-
C O N T R O L L E D, P A R A L L E L G R O U P C O M P A RI S O N S T U D Y T O D E T E R MI N E 
T H E T H E R A P E U TI C E Q UI V A L E N C E  O F G D C 6 9 5 A N D DI C L O F E N A C 
S O DI U M G E L, 3 % I N S U B J E C T S WI T H A C TI NI C K E R A T O S E S
P R O T O C O L N U M B E R:
G D C- 6 9 5- 0 0 1
O RI GI N A L P R O T O C O L: 
A u g ust 1 8, 2 0 1 6
A M E N D M E N T # 1:
J a n uar y 2 6, 2 0 1 7
FI L E N A M E:
S P O N S O R:
Ga ge D e vel o p me nt C o m pa n y, L L C
S P O N S O R R E P R E S E N T A TI V E:
Ga ge D e vel o p me nt C o m pa n y, L L C
M E DI C A L M O NI T O R:
P R O J E C T M A N A G E R:
2 4 H o ur E mer ge nc y Tel e p h o ne N u m ber 
T he i nf or m ati o n c o nt ai ne d i n t his d oc u me nt is c o nfi de nti al a n d pr o priet ar y 
pr o pert y of G a ge D e vel o p me nt C o m p a n y, L L C.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 of 5 9 
S T U D Y A C K N O W L E D G E M E N T 
I  u n derst a n d  t his  pr ot o c ol  c o ntai ns  i nf or m ati o n  t hat  is  c o nfi d e ntial  a n d  pr o prietar y  t o 
Ga ge D e vel o p me nt C o m pa n y, L L C, t he S p o ns or. 
I h a ve rea d t his pr ot oc ol a n d a gree t hat it co nt ai ns all t he details necessar y t o c o n d uct t he 
st u d y  as  descri be d.  I  will  c o n d uct  t his  st u d y f oll o wi n g  t his  pr ot oc ol  a n d  will  ma ke  a 
reas o na bl e eff ort t o c o m plete t he st u d y i n t he ti m e n ote d. 
I will pr o vi de t he c o nte nts of t his pr ot oc ol t o st u d y staff u n der m y direct s u per visi o n t hat 
nee d t o k n o w t he c o nte nts t o c o n d uct t he st u d y. I will disc uss t his i nf or mati o n wit h t he 
st u d y staff t o e ns ure t he y are f ull y i nf or me d a b o ut t he st u d y a n d t he test articles. I will 
pr o vi de  t he  c o nte nts  of  t he  pr ot oc ol  t o  t he  res p o nsi ble  I nstit uti o nal  Re vie w  B o ar d(s). 
T hese  discl os ur es  ma y  be  ma de;  pr o vi de d  t hat   t he  c o nte nts  are  n ot  use d  i n  a n y  ot her 
cli nical  st u d y  a n d  t he y  are  n ot  discl ose d t o  a n y  ot her  pers o n  or  e ntit y  wit h o ut  pri or 
writte n c o nse nt fr o m G a ge De v el o p me nt C o m p a n y, L L C. T his c o n diti o n d oes n ot a p pl y 
t o  discl os ure  re q uire d  b y  g o ver n m e nt  re g ulati o ns  or  la ws.  H o we ver,  I  a gree  t o  gi ve 
pr o m pt n otice t o Ga ge D e vel o p me nt C o m pa n y, L L C of a n y s u c h discl os ure. 
I u n dersta n d t he st u d y m a y be ter mi nate d or e nr oll me nt s us pe n de d at a n y ti me b y G a ge 
De vel o p me nt C o m pa n y, L L C, wit h or wit h o ut ca use, or b y me if it bec o m es necess ar y t o 
pr otect t he i nterests of t h e st u d y s u bjects. 
A n y a d diti o nal i nf or mati o n a d de d t o t his pr ot oc ol is als o co nfi de ntial a n d pr o prietar y t o 
Ga ge  D e vel o p me nt  C o m pa n y,  L L C  a n d  m ust  be  treat e d  i n  t he  sa me  ma n ner  as  t h e 
c o nte nts of t his pr ot oc ol. 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
Pri nte d Na me of Pri n ci pal I n vesti gat or 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
I n v esti gat or Si g nat ure   
  
  
  
Date
Pr ot oc ol n u m ber: G D C- 6 9 5- 0 0 1  
  
  
Site n u m ber:  
Versi o n: 2. 0    
  
  
  
  
Site a d dress: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Date of fi n al versi o n: J a n uar y 2 6, 2 0 1 7
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 of 5 9 
N A M E S  A N D  A D D R E S S E S  O F  D E P A R T M E N T S  A N D/ O R  I N S TI T U TI O N S 
I N V O L V E D I N T H E S T U D Y 
Test Article La b eli n g:
I nstit uti o nal Re vie w B oar d: 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 of 5 9 
P R O T O C O L S Y N O P SI S
Title
A  M ultice nter,  Ra n d o mize d,  D o u ble- Bli n d,  Place b o- C o ntr olle d,  P arallel 
Gr o u p  C o m paris o n  St u d y  t o  Deter mi ne  t he  T hera pe utic  E q ui vale nce  of 
G D C  6 9 5  a n d  Dicl ofe nac  S o di u m  Gel,  3 %  i n  S u bj ects  wit h  Acti nic 
Kerat oses
St u d y T y pe
Bi oe q ui vale nce wit h Cli nical E n d p oi nt
Test Articles
1. 
T est pr o d uct: G D C 6 9 5 ( Ga ge De vel o p me nt C o m pa n y, L L C)
2. 
Refere nce Liste d Dr u g ( R L D): Di cl ofe nac S o di u m Gel, 3 % ( F o u gera)
3. 
Place b o: ve hicle gel ( Ga ge De vel o p me nt C o m pa n y, L L C)
St u d y O bjecti ve
T o  e val uate  t he  safet y  a n d  t hera p e utic  e q ui vale nce  of  G D C  6 9 5  t o 
Dicl ofe nac S o di u m Gel, 3 % a n d t o esta blis h t he s u peri orit y of t he efficac y 
of t hese t w o pr o d ucts o ver t he ve hicle gel (i.e., place b o) i n t he treat me nt of 
acti nic kerat oses ( A K).
St u d y Desi g n
M ultice nter,  ra n d o mize d,  d o u ble- bli n d,  place b o-c o ntr olle d,  parallel  gr o u p 
c o m paris o n.
Tre at me nt Gr o u ps
Eli gi ble  s u bj ects  will  be  ra n d o mize d  ( 1: 1: 1)  t o  treat me nt  wit h  G D C 6 9 5, 
Dicl ofe nac S o di u m Gel, or place b o.
D ur ati o n of Tre at me nt
T wice- dail y a p plicati o n f or 6 0 da ys.
D ur ati o n of St u d y
A p pr o xi matel y  9 0  da ys  ( n ot  i ncl u di n g  a  ma xi m u m  3 0- da y  scree ni n g 
peri o d).
St u d y P o p ul ati o n
Male a n d/ or fe male s u bj ects, a ges 1 8 years a n d ol der wit h acti nic kerat oses 
o n t he face or bal d scal p.
T ot al N u m ber of 
S u bjects
A p pr o xi matel y 6 0 0 s u bj ects will be e nr olle d t o o btai n at least 5 5 8 m o difie d 
i nte nt-t o-treat  ( mI T T)  a n d  at  least  4 1 7  per- pr ot oc ol  ( P P)  s u bj ects  i n  t he 
st u d y.
N u m ber of Sites
A p pr o xi matel y 2 8 sites will p artici pate i n t he st u d y.
I ncl usi o n Criteri a
T o e nter t he st u d y, a s u bj ect m ust meet t he f oll o wi n g criteria:
1. 
Is a n i m m u n oc o m pete nt male a n d/ or n o n- pre g na nt fe male, 1 8 years of 
a ge or ol der. 
2.  
Has  pr o vi de d  writte n  i nf or me d c o nse nt  i ncl u di n g  c o nse nt  t o 
p h ot o gra p h y of t he treat me nt area at Visit 1.
3. 
Is willi n g a n d a ble t o a p pl y t he test article(s) as directe d, c o m pl y wit h 
st u d y i nstr ucti o ns, a n d c o m mit t o all  f oll o w- u p  visits  f or t he d urati o n 
of t he st u d y.
4.  
Has a cli nical dia g n osis of acti nic  kerat oses  wit h at least  fi ve ( 5) a n d 
n o  m ore t ha n te n ( 1 0) cli nicall y  t y pical, visi ble, or pal pa ble, discrete, 
n o n h y per kerat otic, n o n h y pertr o p hic, A K lesi o ns, eac h at least 4 m m i n 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 6 of 5 9 
dia meter, c o ntai ne d wit hi n a c o nti n u o us 2 5 c m 2 treat me nt area l ocate d 
o n t he face (e xcl u di n g ears) or bal d scal p 1. 
5. 
Is  i n  g o o d  ge neral  healt h  a n d  free  of  a n y  disease  state  or  p h ysical 
c o n diti o n t hat mi g ht i m pair e val uati o n of A K lesi o ns or w hic h, i n t he 
i n vesti gat or’s  o pi ni o n,  e x p oses  t he  s u bj ect  t o  a n  u nacce pta ble ris k  b y 
st u d y partici pati o n. 
6. 
If  fe male,  m ust  be  p ost- me n o pa usal 2,  s ur gicall y  sterile3,  or  use  a n 
effecti ve  met h o d  of  birt h  c o ntr ol 4, 5 wit h  a  ne gati ve  uri ne  pre g na nc y 
test ( U P T)6 at t he B aseli ne Visit.
E xcl usi o n Criteri a
A s u bj ect is i neli gi ble t o e nter t he st u d y if he/s he meets o ne or m ore of t he 
f oll o wi n g criteria: 
1. Is  pre g na nt,  breastfee di n g,  or  is  pla n ni n g  t o  bec o me  pre g na nt  or 
breastfee d d uri n g t he st u d y.
2. Is c urre ntl y e nr olle d i n a n i n vesti gati o nal dr u g or de vice st u d y.
3.  
Has  use d  a n  i n vesti gati o nal  dr u g  or  i n vesti gati o nal  de vic e  wit hi n  3 0 
da ys pri or t o t he B aseli ne Visit.
4. 
S u bj ect has  h y per kerat otic,  h y pertr o p hic (i.e., Gra de 3  A Ks), or lar ge 
A Ks of a n y Gra de (e. g., A K > 1 c m 2 i n size) wit hi n t he treat me nt area.
5.  
Has > 1 0 A Ks of a n y size wit hi n t he treat me nt area.
6.  
Has  t he  nee d  or  pla ns  t o  be  e x p ose d  t o  artificial  ta n ni n g  de vices  or 
e xcessi ve s u nli g ht d uri n g t he st u d y.
7. Is  i m m u n os u p presse d  (e. g.,  h u ma n  i m m u n o deficie nc y  vir us,  s yste mic 
mali g na nc y,  graft  h ost  disease,  etc.)  or 
is  ta ki n g  me dic ati o ns  t hat 
s u p press t he i m m u ne s yste m.
8.  
Has  e x perie nce d  a n  u ns ucc essf ul  o utc o me  fr o m  pre vi o us  t o pical 
dicl ofe nac  s o di u m  t hera p y;  a n  u ns uccessf ul  o utc o me  is  defi ne d  as 
“after a reas o na ble t hera pe uti c trial wit h n o c o m plia nce iss ues a n d t he 
1 B al d scal p f or t he p ur p oses of t his st u d y is a scal p  w here t he s u bj ect has l ost t he  maj orit y of t heir hair 
( well o ver 5 0 %) wit hi n t he i nte n de d 2 5 c m2 treat me nt area w here t he scal p is: a) rea dil y visi ble a n d 2) t he 
n u m ber  of  t he  A Ks  i n  t he  treat me nt  area  ca n  be  easil y  see n  a n d  c o u nte d  b y  t he  e val uat or.  It  is  als o 
i m p orta nt t hat b ot h t he site a n d s u bj ect ca n re peate dl y i de ntif y t he treat me nt area t o ass ur e acc urate re peat 
t hera p y b y t he s u bj ect a n d e val uati o n b y t he i n vesti gat or.
2 Defi ne d as a me n orr hea greater t ha n 1 2 c o nsec uti ve m o nt hs i n w o me n 5 0 years of a ge a n d ol der.
3 H ysterect o m y,  bilateral  t u bal  li gati o n  (at  least  si x  m o nt hs  pri or  t o  i nitiati o n  of  treat me nt),  or  bilateral 
o o p h orect o m y.
4 Effecti ve  f or ms  of  birt h  c o ntr ol  i ncl u de  a)  h or m o nal c o ntrace pti ves  [ oral,  i njecta ble,  tra ns der mal,  or 
i ntra va gi nal]  f or  o ne  f ull  c ycl e  (e. g.,  f o ur  t o  ei g ht  wee ks)  or  i ntra uteri ne  de vice  (I U D)  f or  o ne  wee k,  f or 
i nj ecta ble  (e. g.,  De p o- Pr o vera)  t he  re q uire me nt  is  at  least  se ve n  da ys  after  i nj ecti o n,  pri or  t o  test  article 
a p plicati o n, or b) c o n d o m a n d s per mici dal, or dia p hr a g m/cer vical ca p a n d s per mici dal, w hic h are effecti ve 
as  s o o n  as  t he  birt h  c o ntr ol  met h o d  is  a d mi nister e d  pr o perl y.  Ot her  acce pta ble  f or ms  of  birt h  c o ntr ol 
i ncl u de:  a)  a bsti ne nce  f or  s u bj ects  w h o  are  n ot  se x uall y  acti ve  or  b)  if  t he  s u bj ect  is  i n  a  m o n o ga m o us 
relati o ns hi p  wit h  a  part ner  w h o  is  sterile  (e. g.,  a  vasect o m y  perf or me d  at  least  si x  m o nt hs  pri or  t o  t he 
s u bj ect’s  i nitiati o n  of  treat me nt).  S u bj ects  w h o  bec o me  se x uall y  acti ve  or  be gi n  t o  ha ve  relati o ns  wit h  a 
part ner  w h o  is  n ot  sterile  d uri n g  t he  st u d y  m ust  a gree  t o  use  a n  effecti ve  f or m  of  birt h  c o ntr ol  f or  t he 
d urati o n of t he st u d y. 
5 W o me n of c hil d beari n g p ote ntial ( W O C B P) ta ki n g h or m o nal t hera p y m ust be o n treat me nt pri or t o st u d y 
e ntr y, c o nti n ue d per la bel, a n d m ust n ot c ha n ge t heir d osi n g re gi me n d uri n g t he st u d y. 
6 U P Ts m ust ha ve a mi ni m u m se nsiti vit y of 2 5 mI U ß- h C G/ m L.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 7 of 5 9 
t o pical dr u g di d n ot w or k”.
9.  
Has a hist or y of se nsiti vit y t o a n y of t he i n gre die nts i n t he test articles 
i ncl u di n g dicl ofe nac, be nz yl alc o h ol, p ol yet h yle ne gl yc ol m o n o met h yl 
et her  3 5 9,  h yal ur o nate  s o di u m,  s o di u m  p h os p hate  m o n o basic 
a n h y dr o us, s o di u m h y dr o xi de or ot her e xci pie nts i n t he test pr o d uct or 
R L D.
1 0.  Has  si g ns  or  s y m pt o ms  c o nsiste nt  wit h  t he  as piri n  ( A S A)  tria d: 
ast h matic  s u bj ects  w h o  e x perie nce  r hi nitis  wit h  or  wit h o ut  nasal 
p ol y ps, or w h o e x perie nce se vere br o nc h os pas m after ta ki n g as piri n or 
n o nster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds).
1 1.  Use d  t o pical  pr o d uct  ot her  t ha n  t he  assi g ne d  treat me nt  (i ncl u di n g 
m oist urizers,  s u n  scree n,  crea ms,  oi nt me nts,  l oti o ns,  p o w d ers,  or  gels 
a n d ne w bra n ds of ma ke- u p) wit hi n t he selecte d treat me nt area wit hi n 
o ne da y pri or t o t he B aseli ne Visit.
1 2.  Has  use d  t o pical  me dicati o ns:  c ortic oster oi ds,  al p ha  h y dr o x y  aci ds 
(e. g., gl yc olic aci d, lactic aci d, etc. > 5 %), beta h y dr o x y aci d (salic ylic 
aci d  > 2 %),  urea  > 2 %,  5-fl u or o uracil,  dicl ofe nac,  i mi q ui m o d,  i n ge n ol 
me b utate,  a mi n ole v uli nic  aci d  ( A L A)  or  prescri pti o n  reti n oi ds  (e. g., 
tazar ote ne,  a da pale ne,  treti n oi n),  o ver-t he-c o u nter  ( O T C)  pr o d ucts 
la bele d  as  scr u bs  of  a n y  ki n d  w hic h  are  use d  t o  s m o ot h  t he  s ki n  (as 
t he y c o ntai n s o me f or m of e xf olia nt s uc h as n ut s hells, c offe e gr o u n ds,
p ol y mer particles, etc.) wit hi n t he selecte d treat me nt area (face or bal d 
scal p) wit hi n o ne m o nt h pri or t o t he B aseli ne Visit.
1 3.  Has ha d cr y o destr ucti o n or c he m o destr ucti o n, c uretta ge, p h ot o d y na mic 
t hera p y ( P D T), s ur gical e xcisi o n, or ot her treat me nts f or A K wit hi n t he 
selecte d treat me nt area (face or bal d scal p)  wit hi n o ne  m o nt h pri or t o 
t he B aseli ne Visit.
1 4.  Has  use d  s yste mic  c ortic oster oi d  t hera p y  (i ncl u des  i ntra m usc ular  a n d 
i ntra-artic ular  
a d mi nistrati o n),  
i nterfer o n,  
c yt ot o xi c  
dr u gs, 
i m m u n o m o d ulat ors,  i m m u n os u p pressi ve  t hera pies,  or  reti n oi ds  wit hi n 
o ne m o nt h pri or t o t he B aseli ne Visit.
1 5.  Has use d oral is otreti n oi n wit hi n si x m o nt hs pri or t o t he B aseli ne Visit.
1 6.  Has  use d  c he mical  peels,  i ncl u di n g  b ut  n ot  li mite d  t o  al p ha h y dr o x y 
aci d,  beta h y dr o x y  aci d,  bic hl or oacetic  aci d,  tric hl or oacetic  aci d,  a n d 
p he n ol wit hi n t he selecte d treat me nt area (face or bal d scal p) wit hi n si x 
m o nt hs pri or t o t he B aseli ne Visit.
1 7.  Has  ha d  der mat ol o gic  pr oce d ures  or  s ur geries  s uc h  as:  laser 
res urfaci n g,  P U V A  ( Ps orale n  +  ultra vi olet  A)  t hera p y,  ultra vi olet  B 
( U V B)  t hera p y,  or  der ma brasi o n  wit hi n  t he  selecte d  treat me nt  area 
(face or bal d scal p) wit hi n si x m o nt hs pri or t o t he B aseli ne Visit.
1 8.  Has  lesi o ns  s us pici o us  f or  s ki n  ca ncer  (s ki n  ca ncer  n ot  r ule d  o ut  b y 
bi o ps y)  or  u ntreate d  s ki n  ca ncers  wit hi n  t he  selecte d  treat me nt  area 
(face or bal d scal p).
1 9.  Has a n y s ki n pat h ol o g y or c o n diti o n wit hi n t he selecte d tre at me nt area 
(t he  face  or  bal d  scal p)  s uc h  as  at o pic  der matitis,  ecze ma,  ps oriasis, 
r osacea,  s u n b ur n,  or  ot her  c o nf o u n di n g  s ki n  c o n diti o n(s)  t hat,  i n  t he 
i n vesti gat or’s  o pi ni o n,  c o ul d  i nterfere  wit h  t he  e val uati o n  of  t he  test 
article  or  re q uires  t he  use  of  i nterferi n g  t o pical,  s yste mic,  or  s ur gical 
t hera p y.
2 0.  Has  acti ve  gastr oi ntesti nal  ul cerati o n  or  blee di n g  or  has  a  hist or y  of 
gastr oi ntesti nal blee ds d ue t o use of as piri n or ot her N S AI Ds.
2 1.  Has se vere re nal or he patic i m pair me nt.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 8 of 5 9 
2 2.  Has a n y c o n diti o n w hic h, i n t he i n vesti gat or’s o pi ni o n, w o ul d ma ke it 
u nsafe  or  precl u de  t he  s u bj ect’s  a bilit y  t o  f ull y  partici pate  i n  t his 
researc h st u d y.
2 3. Is  u na ble  t o  c o m m u nicate  or  c o o perate  wit h  t he  i n vesti gat or  d ue  t o 
la n g ua ge  pr o ble ms,  p o or  me ntal  de vel o p me nt,  i m pair e d  cere bral 
f u ncti o n, or p h ysical li mitati o ns.
2 4. Is  k n o w n  t o  be  n o nc o m plia nt  or  is  u nli kel y  t o  c o m pl y  wit h  t he 
re q uire me nts  of  t he  st u d y  pr ot oc ol  (e. g.,  d ue  t o  alc o h olis m,  dr u g 
de pe n de nc y, me ntal i nca pacit y) i n t he o pi ni o n of t he i n vesti gat or. 
2 5.  Has bee n pre vi o usl y e nr olle d i n t he sa me st u d y.
St u d y Pr oce d ures
S u bj ects ca n be scree ne d f or t he st u d y u p t o 3 0 da ys bef ore Visit 1. D uri n g 
scree ni n g,  t he  st u d y re q uire me nts  will  be  re vie we d,  writte n  i nf or me d 
c o nse nt o btai ne d, a n d eli gi bilit y c o nfir me d. If a p plica ble, q ualifie d s u bj ects 
ca n  was h o ut  fr o m  pr o hi bite d  me dicati o ns  or  treat me nts  pri or  t o  t heir 
Scree ni n g/ B aseli ne Visit o nce t he y ha ve bee n c o nse nte d. T hese pr oce d ures 
ma y be c o m bi ne d wit h t he B aseli ne Visit.
As part of t he c o nse nt pr ocess it is i m p orta nt t o:
1. 
Re vie w  t he  I R B-a p pr o ve d  i nf or me d  c o nse nt  f or m  wit h  eac h 
p ote ntial s u bj ect a n d pr o vi de t he m wit h a n o p p ort u nit y t o ha ve all 
q uesti o ns a ns were d bef ore pr ocee di n g.
2.  
O btai n  a  si g ne d  I R B-a p pr o ve d  i nf or me d  c o nse nt  fr o m  eac h 
s u bj ect. Writte n i nf or me d c o nse nt m ust be o btai ne d fr o m eli gi ble 
s u bj ects bef ore t he y are e nr olle d i nt o t he st u d y.
T he st u d y will c o nsist of a Scree ni n g/ B aseli ne Visit, tele p h o ne calls at  Da y 
1 5 a n d at Da y 4 5, a n d f oll o w- u p visits at Da y 3 0, Da y 6 0, a n d Da y 9 0 ( 3 0 
da ys after c o m pleti o n of 6 0 da ys of treat me nt).
1.  
Visit 1 - Scree ni n g/ B aseli ne Visit (- 3 0 t o Da y 1): T he f oll o wi n g will 
be  o btai ne d  at  t his  visit:  si g ne d  writte n  i nf or me d  c o nse nt  ( or  re-
c o nse nt  if  was h o ut  peri o d  e xcee ds  3 0  da ys),  c o nfir mati o n  of 
eli gi bilit y,  me dical  hist or y,  de m o gra p hics,  re vie w  of  c o nc o mita nt 
me dicati o ns  a n d  t hera pies/ pr oce d ures,  der mat ol o gic  e xa m,  U P T  (if 
a p plica ble),  i de ntificati o n  of  a nat o mic  treat me nt  area  (t h e  face 
[e xcl u di n g  t he  ears]  or  t he  bal d  scal p),  i de ntificati o n  of  t he 
desi g nate d  2 5  c m 2 treat me nt  area  b y  creati n g  a  “s u bj ect  s pecific” 
te m plate  t o  assist  t he  s u bj ect  i n  i de ntif yi n g  t he  treat me nt  area  f or 
a p plicati o n  of  t he  test  articl e,  A K  c o u nt,  a n d  l ocal  s ki n  reacti o n 
( L S R)  assess me nt.  Q ualifie d  s u bj ects  will  be  ra n d o ml y  assi g ne d  t o 
o ne of t hree treat me nt gr o u ps ( G D C 6 9 5, Dicl ofe nac S o di u m Gel, or 
ve hicle gel). T est article a p pli cati o n will be de m o nstrate d usi n g t he 
n o n- me dicate d  sa m ples  pr o vi de d  t o  t he  site.  T he  s u bj ect  will  be 
i nstr ucte d n ot t o o pe n st u d y s u p plies at t he site. T est article will be 
dis pe nse d, al o n g wit h a p plicati o n i nstr ucti o ns a n d a s u bj ect diar y t o 
d oc u me nt a n y a p plie d, hel d, or misse d d oses. Baseli ne p h ot o gra p hs 
of t he desi g nate d 2 5 c m 2 treat me nt area  will be ta ke n at t he site ( 1 
p h ot o t o re mai n i n t he s u bj ect’s file at t he site a n d 1 p h ot o gi ve n t o 
t he  s u bj ect)  i n  or der  t o  hel p  e ns ure  pr o per  a p plicati o n  of  t he  test 
article  b y  t he  s u bj ect.  A  se parate  Treat me nt  Area  I de ntificati o n 
Ma n ual  wit h  i nstr ucti o ns  o n  h o w  t o  create  t he  “s u bj ect  s pecific” 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 9 of 5 9 
te m plate a n d h o w t o ta ke t he B aseli ne p h ot o gra p hs will be pr o vi de d 
t o t he sites f or use. T he s u bj ects will be i nstr ucte d t o a p pl y t he test 
article t wice dail y, o nce i n t he m or ni n g a n d o nce i n t he e ve ni n g, f or 
6 0  da ys  t o  t he  e ntire  2 5  c m 2 treat me nt  area.  S u bj ects  will  be 
sc he d ule d f or t he ne xt visit.
2.  
Visit 2 - P h o ne Call ( Da y 1 5 ± 3 da ys): T he site staff will c o ntact t he 
s u bj ect o n Da y 1 5 t o c o nfir m t he ne xt visit a p p oi nt me nt, re vie w t he 
s u bj ect  diar y  a n d  test  article  c o m plia nce,  re vie w  of  c o nc o mita nt 
me dicati o ns  a n d  t hera pies/ pr oce d ures,  a n d  q uer y  t he  s u bj ect  a b o ut 
a d verse  e ve nts  ( A Es).  T h e  site  staff  will  re mi n d  t he  s u bj ect  t o 
c o nti n ue  t o  a p pl y  test  article  t wice  dail y,  o nce  i n  t he  m or ni n g  a n d 
o nce i n t he e ve ni n g, t o t he s ki n of t he 2 5 c m 2 treat me nt area u ntil t he 
ne xt  cli nic  visit  a n d  t o  bri n g  t heir  t u be  of  test  article  wit h  t he m  t o 
t heir ne xt  cli nic  visit.  S u bj ects  wit h  se vere  t olera bilit y  iss ues  or  a 
material  A E  c o ncer n  of  a n y  t y pe  ma y  be  see n  f or  a n  i n- office 
f oll o w-u p  as  a n  u nsc he d ul e d  visit  at  t he  discreti o n  of  t he 
i n vesti gat or.
3.  
Visit  3  ( Da y  3 0  ±  3  da ys): S u bj ects  will  ret ur n  f or  re vie w  of 
c o nc o mita nt me dicati o ns a n d t hera pies/ pr oce d ures, L S Rs, a n d A Es. 
T he s u bj ect diar y will be re vie we d/c ollecte d/ distri b ut e d as necessar y 
a n d  test  article  c o m plia nce  will  be  re vie we d  a n d  t he  site  staff  will 
re mi n d t he s u bj ect t o c o nti n ue t o a p pl y test article t wice dail y, o nce 
i n  t he  m or ni n g  a n d  o nce  i n  t he  e ve ni n g,  t o  t he  s ki n  of  t he  2 5  c m2
treat me nt area u ntil t he ne xt cli nic visit. T est article a p plicati o n will 
be  de m o nstrate d  if  dee me d  necessar y.  T he  s u bj ect’s  t u b e  of  test 
article  will  be  wei g he d  a n d  re- dis pe nse d.  T he  s u bj ect  will  be 
sc he d ule d f or t he ne xt f oll o w- u p visit.
4.  
Visit 4 - P h o ne Call ( Da y 4 5 ± 3 da ys): T he site staff will c o ntact t he 
s u bj ect o n Da y 4 5 t o c o nfir m t he ne xt visit a p p oi nt me nt, re vie w t he 
s u bj ect  diar y  a n d  test  article  c o m plia nce,  re vie w  of  c o nc o mita nt 
me dicati o ns  a n d  t hera pies/ pr oce d ures,  a n d  q uer y  t he  s u bj ect  a b o ut 
A Es. T he site staff will re mi n d t he s u bj ect t o c o nti n ue t o a p pl y test 
article t wice dail y, o nce i n t he m or ni n g a n d o nce i n t he e ve ni n g, t o 
t he s ki n of t he 2 5 c m2 treat me nt area u ntil t he ne xt cli nic visit a n d t o 
bri n g  t heir  t u be  of  test  articl e  wit h  t he m  t o  t heir  ne xt  cli nic  visit. 
S u bj ects wit h se vere t olera bilit y iss ues or a material A E c o ncer n of 
a n y  t y pe  ma y be see n f or a n  i n- office  f oll o w- u p as a n  u ns c he d ule d 
visit  at  t he  discreti o n  of  t he  i n vesti gat or. N O T E:  T he  e n d  of 
tre at me nt  visit  s h o ul d  be  sc he d ule d  s uc h  t h at  t he  s u bject  will  h ave 
h a d i de ally 6 0 d ays of tre at me nt.
5.  
Visit 5 – E n d of Treat me nt [ E O T] ( Da y 6 0 + 4 da ys): S u bj ects will 
ret ur n  
f or  
re vie w  
of  
c o nc o mita nt  
me dicati o ns  
a n d 
t hera pies/ pr oce d ures, L S Rs, a n d A Es, U P T (if a p plica ble) as well as 
A K lesi o n c o u nts. T he s u bj ect diar y a n d test article c o m plia nce will 
be  re vie we d  a n d  b ot h  t he  s u bj ect  diar y  a n d  test  article will  be 
c ollecte d. T he s u bj ect will be sc he d ule d f or t he e n d of st u d y visit.
6.  
Visit  6  – E n d  of  St u d y  [ E O S]  ( Da y  9 0  ±  4  da ys): S u bj ects  will 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 0 of 5 9 
ret ur n 3 0 d ays after c o m pleti o n of 6 0 d ays of tre at me nt f or  re vie w 
of  c o nc o mita nt  me dicati o ns  a n d  t hera pies/ pr oce d ures,  L S Rs,  a n d 
A Es,  as  well  as  A K  lesi o n  c o u nts.  T he  s u bj ect  will  be  disc har ge d 
fr o m t he st u d y.
St u d y M e as ure me nts
T he  pri mar y  cli nical  assess me nt  i n  t he  st u d y  is  base d  o n  A K  lesi o n 
cleari n g.
Effic acy
T he pri mar y efficac y para met er is t he n u m ber of all visi ble or pal pa ble A K 
lesi o ns  ( baseli ne  a n d  ne w  lesi o ns)  i n  t he  2 5  c m2 treat me nt  area  as 
e n u merate d  at  B aseli ne  a n d  at  all  f oll o w- u p  visits  b y  t he  i n vesti gat or  or 
desi g nee.
S afety
All  A Es  will  be  rec or de d.  At  eac h  visit,  s u bj ects  will  als o  be  q uesti o ne d 
s pecificall y  a b o ut  a n y  A Es  ass ociate d wit h  t he  a p plicati o n  of  t he  test 
article,  as  well  as  t he  stat us  of  a n y  o n g oi n g  A Es.  I n  a d diti o n,  L S Rs 
i ncl u di n g  
er yt he ma,  
dr y ness/fla ki n g/scali n g,  
b ur ni n g/sti n gi n g, 
er osi o n/ ulcerati o n, e de ma, pai n, a n d pr urit us will be assesse d a n d rec or de d 
se paratel y  at  eac h  o nsite  cli nic  visit  b y  t he  i n vesti gat or  t o  all o w  a 
c o m paris o n bet wee n treat me nt gr o u ps.
St u d y E n d p oi nts
Effic acy E n d p oi nt(s)
T he  pri mar y  efficac y  e n d p oi nt  is  t he  pr o p orti o n  of  s u bj ects  i n  t he  P P 
p o p ulati o n  wit h  treat me nt  s uccess  ( “ C o m plete  Cleara nce”)  at  Da y  9 0  ( 3 0 
da ys  after  c o m pleti o n  of  6 0  da ys  of  treat me nt).  C o m plete  Cleara nce  is 
defi ne d as 1 0 0 % cleara nce of all A K lesi o ns ( ha vi n g a c o u nt of zer o A Ks) 
i n  t he  2 5  c m2 treat me nt  area  (face  or  bal d  scal p)  at  t he  Da y 9 0  visit.  All 
A Ks  (t h ose  prese nt  at  baseli ne  a n d  ne w  lesi o ns,  if  a n y  t hat  ma y  de vel o p) 
i n de pe n de nt of size wit hi n t he 2 5 c m2 treat me nt area are t o be treate d a n d 
i ncl u de d i n t he efficac y lesi o n c o u nt f or eac h visit.
S afety E n d p oi nt(s)
D osi n g C o m plia nce
Meas ures  of  test  article  c o m plia nce  will  i ncl u de  t he  t otal  n u m ber  of 
a p plicati o ns rec or de d i n t he case re p ort f or ms ( C R Fs) a n d verifie d fr o m t he 
data  i n  t he  s u bj ect  diaries.  C o m plia nt  s u bj ects  are  defi ne d  as  t h ose  w h o 
a p pl y at least 7 5 % a n d n o m or e t ha n 1 2 5 % of t he e x pecte d ( 1 2 0) test article 
a p plicati o ns, di d n ot miss m or e t ha n 1 0 c o nsec uti ve sc he d ul e d a p plicati o ns, 
a n d ha ve n o ot her e vi de nce of material d osi n g n o nc o m plia nc e.
A d verse E ve nts a n d L ocal S ki n Reacti o ns
Se verit y  
a n d  fre q ue nc y  
of  
A Es  i ncl u di n g  
L S Rs  (er yt he ma, 
dr y ness/fla ki n g/scali n g,  b ur ni n g/sti n gi n g,  er osi o n/ ulcerati o n,  e de ma,  pai n, 
a n d pr urit us) will be assesse d i n t he t hree treat me nt gr o u ps.
S a m ple Size 
C alc ul ati o ns
B ase d  o
  pr o ba bilit y  of  de m o nstrati n g  t hera pe utic  e q ui vale nc e  bet wee n  t he 
acti ve treat me nts a n d at t he sa me ti me s h o wi n g t hat eac h acti ve treat me nt is 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 1 of 5 9 
s u peri or t o t he ve hicle treat me nt. T h us, a p pr o xi matel y  
 s u bj ects will be 
e nr olle d i nt o t he st u d y t o o btai n  
 mI T T s u bjects.
St atistic al M et h o ds
All  statistical  pr ocessi n g  will  be  perf or me d  usi n g  S A S ® u nless  ot her wise 
state d. 
St u d y P o p ul ati o ns:
T he Safet y p o p ulati o n will i ncl u de all ra n d o mize d s u bjects w h o recei ve d t he 
test  article.  T he  mI T T  p o p ulati o n  will  i ncl u de  all  ra n d o mize d  s u bjects  w h o 
met  all  i ncl usi o n/e xcl usi o n  criteria,  a p plie d  at  least  o ne  d ose  of  test  article, 
a n d  ret ur ne d  f or  at  least  o ne  p ost- baseli ne  e val uati o n  visit.  Ra n d o mize d 
s u bj ects  w h o  are  l ost  t o  f oll o w- u p  after  Visit  1,  w h o  ret ur n  f or  t he  E O T 
visit b ut ha ve n ot a p plie d a n y test article, or w h o are f o u n d n ot t o ha ve met 
t he eli gi bilit y criteria will be e xcl u de d fr o m t he mI T T p o p ulati o n. S u bjects 
will  be  i ncl u de d  i n  t he  P P  efficac y  a nal yses  if  t he y  met  all  t he 
i ncl usi o n/e xcl usi o n  criteria,  were  c o m plia nt  wit h  t he  assi g ne d  test  articles 
(a p plie d  at  least  7 5 %  a n d  n o  m ore  t ha n  1 2 5 %  of  t he  e x pecte d  ( 1 2 0)  test 
article  a p plicati o ns)  f or  t he  s pecifie d  d urati o n  of  t he  st u d y,  di d  n ot  miss 
m ore  t ha n  1 0  c o nsec uti ve  sc he d ule d  a p plicati o ns,  ha ve  n o  ot her  e vi de nce 
of  material  d osi n g  n o nc o m plia nce,  a n d  c o m plete d  t he  pri mar y  e n d p oi nt 
e val uati o n  at  t he  E O S  visit  wit hi n  t he  desi g nate d  visit  wi n d o w  ( ±  4  da ys) 
wit h  n o  pr ot oc ol  vi olati o ns  t hat  w o ul d  affect  t he  treat me nt  e val uati o n. 
S u bjects  w h o  are  disc o nti n ue d  fr o m  t he  st u d y  d ue  t o  w orse ni n g  c o n diti o n 
t hat  re q uires  alter nate  or  s u p ple me ntal  t hera p y  f or  t he  treat me nt  of  A K 
s h o ul d be i ncl u de d i n t he P P p o p ulati o n as treat me nt fail ures if t he y meet t he 
mI T T criteria. S u bjects w h o are disc o nti n ue d earl y fr o m t he st u d y d ue t o lac k 
of  treat me nt  effect  after  c o m pleti n g  at  least  f o ur  wee ks  of  treat me nt  s h o ul d 
be  i ncl u de d  i n  t he  mI T T  a n d  P P  p o p ulati o n  as  treat me nt  fail ures.  S u bjects 
disc o nti n ue d  earl y  f or  ot her  reas o ns  s h o ul d  be  e xcl u de d  fr o m  t he  P P 
p o p ulati o n,  b ut  i ncl u de d  i n  t he  mI T T  p o p ulati o n,  usi n g  last- o bser vati o n-
carrie d-f or war d ( L O C F).
Efficac y  s u m maries  a n d  a nal yses  will  be  carrie d  o ut  i n  t he  mI T T  a n d  P P 
p o p ulati o ns.  All  s u m maries  of  safet y  will  be  carrie d  o ut  i n  t he  Safet y 
p o p ulati o n.  L O C F  will  be  use d  t o  i m p ute  missi n g  val ues  f or  efficac y 
varia bles i n t he mI T T p o p ulati o n. 
De m o gra p hic a n d baseli ne c haracteristics will be s u m mariz e d b y treat me nt 
gr o u p  f or  all  a nal ysis  p o p ulati o ns.  T he  size  of  t he  treat me nt  area  i n  c m 2
will be s u m marize d b y treat me nt gr o u p f or t he mI T T a n d P P p o p ulati o ns. 
Fre q ue nc y  c o u nts  a n d  perce nta ges  will  be  re p orte d  f or  cate g orical  data. 
Sa m ple  size,  mea n,  sta n dar d  de viati o n,  mi ni m u m,  a n d  ma xi m u m  will  be 
re p orte d f or t he c o nti n u o us varia bles.
Effic ac y A n al yses:
T he 9 0 % W al d’s c o nfi de nce i nter val wit h Yate’s c o nti n uit y c orrecti o n will 
be c o nstr ucte d o n t he differe nce bet wee n t he pr o p orti o ns  of s u bj ects  wit h 
A K  lesi o n  cleara nce  i n  t he  Test  a n d  Refere nce  treat me nts  t o  e val uate  t he 
t hera pe utic c o m para bilit y of t he t w o acti ve treat me nts. E val uati o n i n t he P P 
p o p ulati o n will be c o nsi dere d pri mar y.
At Da y 9 0 ( 3 0 da ys after c o m pleti o n of 6 0 da ys of treat me nt), if t he 9 0 % 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 2 of 5 9 
c o nfi de nce  i nter val  o n  t he  differe nce  bet wee n  t he  T est  a n d  Refere nce 
lesi o n  cleara nce  pr o p orti o ns  are  c o ntai ne d  wit hi n  t he  i nter val  - 0. 2 0  t o 
+ 0. 2 0,  t he n  t he  T est  a n d  R efere nce  pr o d ucts  will  be  c o nsi dere d  t o  be 
t hera pe uticall y e q ui vale nt.
T w o-si de d,  c o nti n uit y-c orrect e d  C hi-s q uare  tests  will  be  use d  t o  e val uate 
t he  s u peri orit y  of  eac h  acti ve  treat me nt’s  c o m plete  clear a nce  pr o p orti o n 
o ver t hat of t he Ve hicle treat me nt i n t he mI T T p o p ulati o n usi n g L O C F.
T he  t hera pe utic  c o m para bilit y  e val uati o ns  i n  t he  P P  p o p ulati o n  will  be 
c o nsi dere d pri mar y, w hile t h ose i n t he mI T T p o p ulati o n will be c o nsi dere d 
s u p p orti ve.  T he  s u peri orit y  c o m paris o ns  i n  t he  mI T T  p o p ulati o n  will  be 
c o nsi dere d  pri mar y  w hile  t h ose  i n  t he  P P  p o p ulati o n  will  be  c o nsi dere d 
s u p p orti ve.
S afet y A n al yses:
All s u bjects i n t he Safet y p o p ulati o n will be i ncl u de d i n s u m maries of safet y 
data. 
D osi n g C o m plia nce
Descri pti ve statistics will be use d t o s u m marize test article c o m plia nce f or 
t he  mI T T  a n d  P P  p o p ulati o ns.  Meas ures  of  test  article  c o m plia nce  will
i ncl u de  t he  t otal  n u m ber  of  a p plicati o ns  as  deter mi ne d  fr o m  t he  data 
rec or de d i n t he s u bj ect diaries. C o m plia nt s u bj ects are defi ne d as t h ose w h o 
a p pl y at least 7 5 % a n d n o m or e t ha n 1 2 5 % of t he e x pecte d ( 1 2 0) test article 
a p plicati o ns, di d n ot miss m or e t ha n 1 0 c o nsec uti ve sc he d ul e d a p plicati o ns, 
a n d ha ve n o ot her e vi de nce of material d osi n g n o nc o m plia nc e.
A d verse E ve nts
All  A Es  will  be  c o de d  usi n g  t he  Me dical  Dicti o nar y  f or  Re g ulat or y 
Acti vities ( Me d D R A) c o di n g dicti o nar y. T he n u m ber a n d perce nt of u ni q ue
s u bj ects  re p orti n g  eac h  treat me nt-e mer ge nt  A E  will  be  s u m marize d  b y 
Me d D R A  s yste m  or ga n  class  ( S O C),  Me d D R A  preferre d  ter m  ( P T),  a n d 
treat me nt  gr o u p.  A Es  will  als o  be  si milarl y  s u m marize d  b y  S O C,  P T, 
ma xi m u m  se verit y,  a n d  treat me nt  gr o u p  as  well  as  b y  S O C,  P T,  cl osest 
relati o ns hi p  t o  test  article,  a n d  treat me nt  gr o u p.  All  A Es  r e p orte d  d uri n g 
t he  st u d y  will  be  liste d,  d oc u me nti n g  c o urse,  se verit y,  i n vesti gat or 
assess me nt of t he relati o ns hi p t o t he test articles, a n d o utc o me. 
L ocal S ki n Reacti o ns
T he  fre q ue nc y  of  t he  i n di vi d ual  L S Rs  (er yt he ma,  dr y ness/fla ki n g/scali n g, 
b ur ni n g/sti n gi n g,  er osi o n/ ulc erati o n,  e de ma,  pai n,  a n d  pr urit us)  will  be 
ta b ulate d b y se verit y a n d treat me nt gr o u p at eac h o nsite cli nic visit.
I nteri m A n al ysis
N o i nteri m a nal ysis is pla n ne d.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 3 of 5 9 
S C H E D U L E O F E V E N T S
Visit/ C o nt act
Visit 1
Scree ni n g/
B aseli ne
Visit 2
Tele p h o ne
Visit 3
F oll o w-
u p
Visit 4
Tele p h o ne
Visit 5
E n d of 
Tre at me nt
Visit 6
E n d of St u d y 7
3 0 D a ys P ost-
Tre at me nt 
F oll o w- u p
Da y
1
Da y 1 5
( ± 3 da ys)
Da y 3 0
( ± 3 da ys)
Da y 4 5
( ± 3 da ys)
Da y 6 0
( + 4 da ys)
Da y 9 0
( 4 da ys)
Treat me nt P eri o d
Test Article A p plic ati o n T wice D ail y f or 6 0 
C o nsec uti ve D a y s.
I nf or me d C o nse nt 8
X
Me dical Hist or y & 
De m o gra p hics
X 
C o nc o mita nt 
Me dicati o ns a n d 
T hera pies / Pr oce d ures
X  
X  
X  
X 
X 
X 
Der mat ol o g y E xa m  
X
Eli gi bilit y Scree ni n g, 
I ncl usi o n, E xcl usi o n
X 
I de ntificati o n of 2 5 c m2
treat me nt area ( Face or 
B al d Scal p 9) - L ocati o n 
& Size
X 
P h ot o gra p h y & “ S u bj ect 
S pecific” T e m plate 1 0
X 
A K Lesi o n E val uati o n 
& C o u nti n g
X 
X 
X 
L S R Assess me nt
X
X
X
X
A d verse E ve nts
X  
X  
X  
X
X
X
7 S u bj ects w h o ter mi nate earl y s hall c o m plete all fi nal visit acti vities desi g nate d at Da y 9 0.
8 S u bj ects  ma y  ha ve  c o nse nt  si g ne d  a n d  if  re q uire d  was h- o ut  fr o m  pr o hi bite d  me dicati o ns  or  treat me nts 
wit hi n 3 0 da ys pri or t o t he B aseli ne Visit.
9 B al d scal p f or t he p ur p oses of t his st u d y is a scal p  w here t he s u bj ect has l ost t he  maj orit y of t heir hair 
( well o ver 5 0 %) wit hi n t he i nte n de d 2 5 c m2 treat me nt area w here t he scal p is: a) rea dil y visi ble a n d 2) t he 
n u m ber  of  t he  A Ks  i n  t he  treat me nt  area  ca n  be  easil y  see n  a n d  c o u nte d  b y  t he  e val uat or.  It  is  als o 
i m p orta nt t hat b ot h t he site a n d s u bj ect ca n re peate dl y i de ntif y t he treat me nt area t o ass ur e acc urate re peat 
t hera p y b y t he s u bj ect a n d e val uati o n b y t he i n vesti gat or.
1 0 A Treat me nt Area I de ntificati o n Ma n ual will be pr o vi de d t o t he sites wit h i nstr ucti o ns o n h o w t o perf or m 
p h ot o gra p h y of t he treat me nt area a n d o n h o w t o create t he “s u bj ect s pecific” te m plate.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 4 of 5 9 
Visit/ C o nt act
Visit 1
Scree ni n g/
B aseli ne
Visit 2
Tele p h o ne
Visit 3
F oll o w-
u p
Visit 4
Tele p h o ne
Visit 5
E n d of 
Tre at me nt
Visit 6
E n d of St u d y 7
3 0 D a ys P ost-
Tre at me nt 
F oll o w- u p
Da y
1
Da y 1 5
( ± 3 da ys)
Da y 3 0
( ± 3 da ys)
Da y 4 5
( ± 3 da ys)
Da y 6 0
( + 4 da ys)
Da y 9 0
( 4 da ys)
Pre g na nc y T esti n g 1 1 f or 
W O C B P
1 2
X 
X 
A p plicati o n I nstr ucti o ns 
Distri b ute d
X 
T est Article A p plicati o n 
De m o nstrati o n
X 
Ra n d o mizati o n
X
S u bj ect Diar y 
Distri b ute d
X 
X 
S u bj ect Diar y Re vie we d
X  
X  
X
X
S u bj ect Diar y C ollecte d
X
X
T est Article C o m plia nce 
C hec k
X  
X  
X 
X 
T est Article 
Acc o u nta bilit y 
( T est Article 
Dis pe nsi n g)
X 
X 
T est Article 
Acc o u nta bilit y 
( T est Article Ret ur n)
X 
1 1 U P Ts m ust ha ve a mi ni m u m se nsiti vit y of 2 5 mI U ß- h C G/ m L.
1 2 W O C B P i ncl u de a n y fe male w h o has e x perie nce d me narc he or is 1 0 years of a ge or ol der a n d w h o has 
n ot  u n der g o ne  s uccessf ul  s ur gical  sterilizati o n  ( h ystere ct o m y,  bilateral  t u bal  li gati o n,  or  bilateral 
o o p h orect o m y) or is n ot p ost me n o pa usal ( defi ne d as a me n orr hea > 1 2 c o nsec uti ve  m o nt hs i n  w o me n 5 0 
years of a ge or ol der). E ve n w o me n w h o are usi n g oral , i m pla nte d, i nj ecta ble, i ntra va gi nal c o ntrace pti ve 
h or m o nes, a n I U D, barrier met h o ds ( dia p hra g m/cer vica l ca p a n d s per mici dal, c o n d o m a n d s per mici dal) t o 
pre ve nt pre g na nc y, practici n g a bsti ne nce, or w here t he part ner is sterile a n d t he s u bj ect states s he is i n a 
m o n o ga m o us  relati o ns hi p  s h o ul d  be  c o nsi dere d  t o  be  of  c hil d beari n g  p ote ntial.  S ur gical  mea ns  of 
sterilizati o n  (e. g.,  vasect o m y,  t u bal  li gati o n)  m ust  be  a  mi ni m u m  of  si x  m o nt hs  p ost- pr oce d ure  t o  be 
c o nsi dere d effecti ve birt h c o ntr ol. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 5 of 5 9 
A B B R E VI A TI O N S
A E  
A d verse E v e nt
A K  
Acti nic Kerat oses
A L A  
A mi n ole v uli nic Aci d
A S A  
Acet ylsalic ylic Aci d
β - h C G 
Beta- H u ma n C h ori o nic G o na d otr o pi n
C F R 
C o de of Fe d eral Re g ul ati o ns
C LI A 
Cli nical La b orat or y I m pr o ve me nt A me n d me nts
c m 
Ce nti meter
C O X- 2 
C ycl o o x y ge n ase- 2
(e) C R F 
(electr o ni c) Case Re p ort F or m
E D C 
Electr o nic D ata Ca pt ure
E O S 
E n d of St u d y
E O T 
E n d of Treat me nt
F D A 
F o o d a n d Dr u g A d mi nistrati o n
G D C 6 9 5  
Dicl ofe nac s o di u m gel, 3 % ( Ga ge De v el o p me nt C o m pa n y)
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n
I R B 
I nstit uti o nal Re vie w B oar d
I U D 
I ntr a uteri ne De vice
L O C F 
Last O bs er vati o n Carrie d F or w ar d
L S R 
L ocal S ki n Reacti o n
Me d D R A  
Me dical Dicti o nar y f or R e g ul at or y Acti vities
mI T T  
M o difie d I nte nt-t o- Treat
N S AI Ds  
N o n- Ster oi dal A nti-I nfla m mat or y Dr u gs
O T C  
O ver-t he- C o u nter
P D T 
P h ot o d y n a mic T hera p y
P P 
Per- Pr ot oc ol
P T 
Preferre d Ter m
P U V A 
Ps orale n + Ultra vi olet A
R L D 
Refere n ce Liste d Dr u g
S A E 
Seri o us A d verse E v e nt
S O C
S yste m Or ga n Class
U P T
Uri ne Pre g na n c y Test
U V B
Ultra vi olet B
W O C B P  
W o me n of C hil d beari n g P ote ntial

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 6 of 5 9 
T A B L E O F C O N T E N T S
Pr ot oc ol A p pr o val ............................................................................................................. .. 2 
St u d y Ac k n o wle d ge me nt .................................................................................................... 3  
Na mes a n d A d dresses of De pa rt me nts a n d/ or I nstit uti o ns I n v ol ve d i n t he St u d y .............. 4 
Pr ot oc ol S y n o psis.............................................................................................................. .. 5 
Sc he d ule of E ve nts ............................................................................................................  1 3 
A b bre viati o ns ................................................................................................................. ... 1 5 
Ta ble of C o nte nts ............................................................................................................. . 1 6 
1.  
Bac k gr o u n d ....................................................................................................... 1 9  
2.  
Rati o nale ........................................................................................................... 1 9  
3.  
O bjecti ves ......................................................................................................... 2 0  
4.  
St u d y Desi g n ..................................................................................................... 2 0  
5.  
St u d y P o p ulati o n ............................................................................................... 2 0  
5. 1  
S u bject Eli gi bilit y ............................................................................................. 2 0  
5. 1. 1  
I n cl usi o n Criteria ....................................................................................... 2 0 
5. 1. 2  
E x cl usi o n Criteria ...................................................................................... 2 1  
5. 1. 3  
S u bject Wit h dra wal Criteria ...................................................................... 2 3  
6.  
Test Articles a n d Re gi me n ................................................................................ 2 3  
6. 1  
Descri pti o n ........................................................................................................ 2 3  
6. 2  
I nstr u cti o ns f or Use a n d A p plicati o n ................................................................ 2 4 
6. 3  
War ni n gs, Preca uti o ns a n d C o ntrai n dicati o ns .................................................. 2 4  
6. 3. 1  
C o ntrai n dicati o ns ....................................................................................... 2 4  
6. 3. 2  
War ni n gs .................................................................................................... 2 4  
6. 3. 3  
Preca uti o ns................................................................................................. 2 5  
6. 3. 4  
Ot her C o nsi derati o ns ................................................................................. 2 5  
7.  
Ra n d o mizati o n Assi g n me nt .............................................................................. 2 5  
8.  
Pri or a n d C o nc o mita nt T hera pies ..................................................................... 2 5  
8. 1  
Pr o hi bite d Me dicati o ns or T hera pi es ................................................................ 2 6  
8. 2  
All o we d Me dicati o ns or T hera pies ................................................................... 2 7  
9.  
St u d y Pr o ce d ur es .............................................................................................. 2 7  
9. 1  
Visit 1 (- 3 0 t o Da y 1): Scree ni n g/ Baseli ne ....................................................... 2 8  
9. 2  
Visit 2 ( Da y 1 5 ± 3 d a ys): P h o ne Call .............................................................. 2 9  
9. 3  
Visit 3 ( Da y 3 0 ± 3 d a ys): F oll o w- U p .............................................................. 2 9  
9. 4  
Visit 4 ( Da y 4 5 ± 3 d a ys): P h o ne Call .............................................................. 3 0  
9. 5  
Visit 5 ( Da y 6 0 + 4 da ys): E n d of Treat me nt.................................................... 3 0  
9. 6  
Visit 6 ( Da y 9 0 ± 4 d a ys): E n d of St u d y ........................................................... 3 1  
9. 7  
U nsc he d ule d Visit ............................................................................................. 3 1  
1 0.  
Cli nical E val uati o ns .......................................................................................... 3 1  
1 0. 1  
Acti nic Ker at oses Lesi o n C o u nts ...................................................................... 3 2  

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 7 of 5 9 
1 0. 2  
L ocal S ki n Reacti o n Ass ess me nt ...................................................................... 3 2  
1 1.  
P h ot o gra p h y ...................................................................................................... 3 3  
1 2.  
La b orat or y T ests ............................................................................................... 3 3  
1 2. 1  
Uri ne Pre g na n c y Tests ...................................................................................... 3 3  
1 3.  
E n d of St u d y Criteria ........................................................................................ 3 3  
1 3. 1  
C o m pleti o n of t he St u d y ................................................................................... 3 3  
1 3. 2  
S u bject Disc o nti n uati o n .................................................................................... 3 3  
1 3. 3  
St u d y Ter mi nati o n ............................................................................................ 3 4  
1 4.  
A d verse E v e nt Re p orti n g .................................................................................. 3 4  
1 4. 1  
A d verse E v e nt Defi niti o ns ................................................................................ 3 4  
1 4. 2  
A d verse E v e nt Details....................................................................................... 3 6  
1 4. 3  
Seri o us A d verse E v e nt ...................................................................................... 3 7  
1 4. 4  
La b orat or y T est A b n or m alities ......................................................................... 3 9  
1 4. 5  
Pre g n a nc y .......................................................................................................... 3 9  
1 5.  
Bli n di n g/ U n bli n di n g ......................................................................................... 4 0  
1 6.  
Cli nical S u p plies ............................................................................................... 4 0  
1 6. 1  
Test Article I nf or mati o n ................................................................................... 4 0  
1 6. 2  
S u p plies Pr o vi de d b y 
............................................................ 4 0 
1 6. 3  
S u p plies Pr o vi de d b y I n v esti gat or .................................................................... 4 1  
1 6. 4  
S u p plies Pr o vi de d b y Ga ge De vel o p me nt C o m pa n y, L L C .............................. 4 1  
1 7.  
Statistical C o nsi derati o ns .................................................................................. 4 1  
1 7. 1  
Sa m ple Size ....................................................................................................... 4 1  
1 7. 2  
E n d p oi nts .......................................................................................................... 4 1  
1 7. 2. 1  
Efficac y E n d p oi nts .................................................................................... 4 1  
1 7. 2. 2  
Safet y E n d p oi nts ........................................................................................ 4 1  
1 7. 3  
Statistical Met h o ds ............................................................................................ 4 2  
1 7. 3. 1  
Efficac y A n al yses ...................................................................................... 4 2  
1 7. 3. 2  
Safet y A nal yses ......................................................................................... 4 3  
1 7. 3. 2. 1  
D osi n g C o m plia nce ............................................................................. 4 3  
1 7. 3. 2. 2  
A d verse E v e nts .................................................................................... 4 3  
1 7. 3. 2. 3  
L ocal S ki n Reacti o ns ........................................................................... 4 3  
1 7. 4  
S u b gr o u p A n al ys es ........................................................................................... 4 3  
1 7. 5  
I nteri m A nal yses ............................................................................................... 4 4 
1 8.  
Et hical a n d Re g ulat or y C o nsi derati o ns ............................................................. 4 4  
1 8. 1  
C o m plia nce wit h G o o d Cli nical Practice .......................................................... 4 4  
1 8. 2  
I nstit uti o nal Re vie w B oar d a n d I nf or me d C o nse nt .......................................... 4 4 
1 8. 3  
Pr ot oc ol C o m plia nce ......................................................................................... 4 4  
1 8. 4  
Pr ot oc ol Re visi o ns ............................................................................................ 4 5  
1 8. 5  
St u d y M o nit ori n g .............................................................................................. 4 5  
1 8. 6  
Case Re p ort F or m Re q uire me nts ...................................................................... 4 5  
1 8. 7  
Re p orts t o I nstit uti o nal Re vie w B o ar d .............................................................. 4 6  

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 8 of 5 9 
1 8. 8  
Q ualit y Ass ur a nce A u dits ................................................................................. 4 6  
1 8. 9  
Rec or ds Rete nti o n ............................................................................................. 4 6  
1 8. 1 0  Rec or d C o nfi de ntialit y ...................................................................................... 4 7  
1 9.  
Refere n ces ......................................................................................................... 4 8  
A p pe n di x 1  
Sa m ple S u bject I nstr u cti o n S heet .............................................................. 4 9  
A p pe n di x 2  
Test Article I nf or mati o n ............................................................................ 5 3  
A 2. 1  Test Article Pac k a gi n g a n d La b eli n g ................................................................ 5 3  
A 2. 2  Retai ns............................................................................................................... 5 3  
A 2. 3  Test Article St ora ge a n d Pre parati o n ................................................................ 5 4  
A 2. 4  Dis pe nsi n g T est Article..................................................................................... 5 4  
A 2. 5  Test Article S u p pl y Rec or ds at St u d y Sites ...................................................... 5 4  
A 2. 6  D ose M o dificati o ns ........................................................................................... 5 4  
A 2. 7  D oc u me ntati o n of A p plic ati o n a n d C o m plia nce............................................... 5 4  
A 2. 8  Ret ur n a n d Destr u cti o n of Test Article S u p plies .............................................. 5 5  
A p pe n di x 3  
Pr ot oc ol A me n d me nts ............................................................................... 5 6  

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 1 9 of 5 9 
1. 
B A C K G R O U N D
Acti nic ker at oses  ( A Ks)  are  c o m m o n  s ki n  lesi o ns  w hic h  a p p ear  as  s cal y  or  cr ust y 
gr o wt hs  o n  t he  bal d  s cal p,  face,  ears,  li ps,  bac ks  of  t he  ha n ds  a n d  f orear ms,  s h o ul ders, 
nec k, or a n y ot her areas of t he b o d y fre q u e ntl y  e x p ose d t o t he s u n. T he lesi o ns a p pear as 
i n visi ble  or  s u bcli nical lesi o ns,  as  w ell  as visi ble  o nes  o n  t he  s ki n  s urface.  Wit h o ut 
treat me nt, A K(s) ma y re mai n u nc ha n ge d, s p o nta n e o usl y re gress, or pr o gress t o s q ua m o us 
cell  car ci n o ma.  It  is  u n k n o w n  w hic h  A K(s)  wi ll  de vel o p  i nt o  ca ncer  s o  pre ve ntati ve 
treat me nt  strat e gies  ar e  warra nte d.  A K treat me nts  i ncl u de:  t o pical  me dicati o ns, 
cr y os ur ger y,  c o m bi nati o n  t hera pies,  c he mical  peels,  laser  s ur ger y,  a n d  p h ot o d y na mic 
t hera p y.  T o pical  me dicati o ns  i ncl u de:  5-flu or o uracil,  i mi q ui m o d,  i n ge n ol  me b utate,  a n d 
dicl ofe nac. 
T w o  i m p orta nt  sta ges  i n  t he  pr o p ose d  de vel o p m e nt  of  A Ks  ha ve  b ee n  i de ntifie d  as  a 
m utati o n  of  t he  p 5 3  t u m or  s u p press or  ge n e  a n d  a n  i ncrease  i n  t he  c ycl o o x y ge nase- 2 
( C O X- 2) e nz y me (s h o w n at i ncreas e d le vels i n pre mali g na nt a n d m ali g na nt t u m ors) [1 ].  
T he  maj orit y  of  A Ks  i n  t he  U nite d  States  ar e  treate d  b y  destr ucti ve  t hera pies,  s uc h  as 
cr y os ur ger y  [ 2 ].  A  li miti n g  fact or  of  t hese  treat me nt  m o dalities  is  t he  f oc us  o n  treati n g 
discrete lesi o ns, w hic h is i m practical f or us e o n earl y or s u bcli nical A Ks. T o pical a ge nts 
ma y b e better s uite d f or treati n g wi der p h ot o d a ma ge d areas of s u bcli nical lesi o ns. 
Dicl ofe nac s o di u m gel, 3 % is a t o pical n o nste r oi dal a nti-i nfla m mat or y a ge nt t hat is use d 
f or  t he  treat me nt  of  A Ks.  T his  t hera p y  i n hi bits  C O X- 2  le vels  t here b y  bl oc ki n g  t h e  A K 
de vel o p me nt  pat h wa y  [ 3 ].  Dicl ofe nac  s o di u m  gel,  3 %  pr o vi des  a  t o pical  treat me nt 
alter nati ve f or treati n g t he fiel d of p h ot o da ma ge d s ki n b y i n hi biti n g t he f or mati o n of ne w, 
earl y A K lesi o ns i n a d diti o n t o pr o vi di n g tar get e d treat me nt of clearl y visi ble lesi o ns. 
Dicl ofe nac  S o di u m  Gel,  3 %  ( F o u gera )  was  a p pr o ve d  b y  t h e  F o o d  a n d  Dr u g 
A d mi nistrati o n  ( F D A)  i n  2 0 0 0  f or  t he  t o pical  treat me nt  of  A K  [ 4 ].  T he  F D A-a p pr o ve d 
re gi me n f or t he treat me nt of A Ks is a p plicatio n of dicl ofe nac s o di u m gel, 3 % t wice a da y 
t o lesi o n areas wit h a rec om me n de d d urati o n of t h era p y fr o m 6 0 da ys t o 9 0 da ys.  
A  ge neric  dicl of e nac  s o di u m  gel,  3 % 
( G D C  6 9 5)  has  b ee n  d e vel o pe d  b y  Ga ge 
De vel o p me nt  C o m pa n y,  L L C  f or  t he  t o pical  trea t me nt  of  cli nicall y  t y pi cal,  visi ble,  or 
pal pa ble, discrete, n o n h y per kera t otic, n o n h y p ertr o p hic, A K lesi o ns, eac h at least 4 m m i n 
dia meter,  c o ntai ne d  wi t hi n  a  c o nti n u o us  2 5  c m2 treat me nt  area  l ocat e d  o n  t he  face 
(e x cl u di n g ears) or b al d scal p.
2.  
R A TI O N A L E
Ga ge  D e vel o p me nt  C o m pa n y,  L L C  has  de v el o pe d  G D C  6 9 5,  a  ge n eric  dicl ofe nac 
s o di u m  gel,  3 %  f or m ulati o n,  a n d  t he  c urre nt  cli nical  st u d y  is  desi g ne d  t o  e val uat e  t he 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 0 of 5 9 
t hera pe utic  e q ui vale n ce  of  t his  f or m ulati o n  wit h  t he  c urre ntl y  m ar k ete d  Dicl ofe n ac 
S o di u m Gel, 3 % f or m ulati o n ( F o u gera). 
3.  
O B J E C TI V E S
T he  o bjecti ves  of  t he  st u d y  are  t o  e val uate  t he  safet y  a n d  t hera p e utic  e q ui vale nce  of 
G D C 6 9 5 t o Dicl of e nac S o di u m Gel, 3 % ( F o u gera) a n d t o est a blis h t he s u peri orit y of t h e 
efficac y of t hes e t w o pr o d ucts o ver t he ve hi cle gel i n t he treat me nt of A Ks.
4. 
S T U D Y D E SI G N
T his  is  a  m ultice nter,  ra n d o mize d,  d o u ble- bli n d,  place b o-c o ntr olle d,  p arallel  gr o u p 
c o m paris o n  st u d y  of  G D C  6 9 5  a n d  Dicl ofe nac  S o di u m  Gel,  3 %  ( F o u gera)  i n  s u bjects 
wit h A Ks o n t h e f ace or bal d scal p. A p pr o xi mat el y 6 0 0 s u bjects wit h at least fi ve b ut n o 
m ore  t ha n  1 0  cli nicall y  t y pical,  visi bl e  or  pal pa ble,  discrete,  n o n h y per kerat otic, 
n o n h y pertr o p hic,  A K  lesi o ns,  eac h  at  least  4  m m  i n  dia meter,  c o ntai ne d  wit hi n  a 
c o nti n u o us  2 5  c m 2 treat me nt  area  l ocat e d  o n  t h e  face  (e x cl u di n g  t he  ears)  or  t he  bal d 
scal p  w h o  f ulfill  t he  i n cl usi o n/e x cl usi o n  criteria  will  be  e nr olle d  at  a p pr o xi matel y  2 8 
sites.  S u bjects  will  be  ra n d o mize d  t o  o ne  of  t hree  treat me nt  gr o u ps  o n  a  1: 1: 1  basis  as 
f oll o ws: 
1.  G D C 6 9 5 ( Ga ge) ( ge n eri c dicl ofe nac s o di u m gel) 
2.  Dicl ofe nac S o di u m Gel, 3 % ( F o u ge ra) ( Refere n ce Liste d Dr u g [ R L D])
3.  Ve hicle gel ( Ga ge)
All  s u bjects  will  be  i nstr ucte d  t o  a p pl y  t h e  assi g ne d  test  article  t o  t he  e ntire  2 5  c m 2
treat me nt area (face [e x cl u di n g ears] or bal d s cal p) i de ntifie d b y t he i n vesti gat or at Visit 
1. T he assi g ne d test article will be a p plie d t wice dail y, o nce i n t he m or ni n g a n d o n ce i n 
t he e ve ni n g, f or 6 0 da ys t o t he e ntire 2 5 c m2 treat me nt area. T he st u d y will c o nsist of a 
Scree ni n g/ Baseli ne Visit, tele p h o ne  calls at D a y 1 5 a n d at Da y 4 5, a n d f oll o w- u p visits at 
Da y 3 0, D a y 6 0, a n d D a y 9 0 ( 3 0 da ys aft er c o m pleti o n of 6 0 da ys of treat me nt).  At t he 
e n d of t he st u d y, safet y a n d efficac y o ut c o me meas ures will be c o m pare d t o a) deter mi ne 
if  d osi n g  wit h  G D C  6 9 5  is  cli nicall y  e q ui vale nt  t o  t he  c urre ntl y  m ar kete d  Dicl ofe n ac 
S o di u m Gel, 3 % a n d b) b ot h dicl ofe nac s o di u m  3 % gels are s u peri or i n c o m paris o n t o t he 
ve hicle gel.
5. 
S T U D Y P O P U L A TI O N
5. 1 
S u bject Eli gi bilit y
T o be i ncl u de d i n t he st u d y, s u bjects m ust meet t he f oll o wi n g i ncl usi o n a n d n o ne of t he 
e x cl usi o n criteria.
5. 1. 1 I ncl usi o n Criteri a
1. Is a n i m m u n oc o m pete nt male a n d/ or n o n- pre g na nt fe male, 1 8 years of a ge or ol der.  

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 1 of 5 9 
2.  Has  pr o vi de d  writte n  i nf or me d  c o ns e nt i nc l u di n g  c o ns e nt  t o  p h ot o gra p h y  of  t he 
treat me nt ar ea at Visit 1.
3. Is  willi n g  a n d  a ble  t o  a p pl y  t h e  test  articl e(s)  as  directe d,  c o m pl y  wit h  st u d y 
i nstr ucti o ns, a n d c o m mit t o all f oll o w- u p visits f or t he d urati o n of t he st u d y. 
4.  Has a cli nical di a g n osis of acti nic kerat oses wit h at least fi ve ( 5) a n d n o m ore t ha n te n 
( 1 0)  cli nicall y  t y pi cal,  visi ble,  or  p al pa ble,  discret e,  n o n h y p er kerat otic, 
n o n h y pertr o p hic,  A K  lesi o ns,  eac h  at  least  4 m m  i n  dia meter,  c o ntai ne d  wit hi n  a 
c o nti n u o us 2 5 c m 2 treat me nt area l o cate d o n t he face (e x cl u di n g ears) or b al d scal p1 3.
5. Is i n g o o d ge n eral healt h a n d free of a n y di seas e state or p h ysical c o n diti o n t hat mi g ht 
i m pair e val uati o n of A K lesi o ns or w hic h, i n t he i n vesti gat or’s o pi ni o n, e x p oses t he 
s u bject t o a n u nacce pta bl e ris k b y st u d y p artici pati o n.  
6. If fe mal e, m ust be p ost- me n o pa usal 1 4, s ur gicall y sterile1 5, or use a n effecti ve met h o d 
of birt h c o ntr ol 1 6, 1 7 wit h a ne gati ve uri ne pre g na nc y t est ( U P T)1 8 at t he Baseli ne Visit.
5. 1. 2 
E xcl usi o n Criteri a
1. Is pr e g na nt, br eastfee di n g, or is pla n ni n g t o bec o me pre g na nt or breastfee d d uri n g t he 
st u d y.
2. Is c urr e ntl y e nr olle d i n a n i n vesti gati o nal dr u g or de vice st u d y. 
3.  Has use d a n i n vesti gati o nal dr u g or i n vesti gati o n al de vice wit hi n 3 0 da ys pri or t o t he 
Baseli ne Visit.
4. S u bject  has  h y p er k erat otic,  h y p ertr o p hic (i.e.,  Gra de  3  A Ks),  or  lar ge  A Ks  of  a n y 
Gra de (e. g., A K > 1 c m 2 i n size) wit hi n t he treat me nt area.
5.  Has > 1 0 A Ks of a n y size wit hi n t he treat me nt area.
1 3 B al d scal p f or t he p ur p oses of t his st u d y is a scal p w here t he s u bj ect has l ost t he maj orit y of t heir hair 
( well o ver 5 0 %) wit hi n t he i nte n de d 2 5 c m2 treat me nt area w here t he scal p is: a) rea dil y visi ble a n d 2) t he 
n u m ber  of  t he  A Ks  i n  t he  treat me nt  area  ca n  be  easil y  see n  a n d  c o u nte d  b y  t he  e val uat or.  It  is  als o 
i m p orta nt t hat b ot h t he site a n d s u bj ect ca n re peate dl y i de ntif y t he treat me nt area t o ass ur e acc urate re peat 
t hera p y b y t he s u bj ect a n d e val uati o n b y t he i n vesti gat or.
1 4 Defi ne d as a me n orr hea greater t ha n 1 2 c o nsec uti ve m o nt hs i n w o me n 5 0 years of a ge a n d ol der.
1 5 H ysterect o m y,  bilateral  t u bal  li gati o n  (at  least  si x  m o nt hs  pri or  t o  i nitiati o n  of  treat me nt),  or  bilateral
o o p h orect o m y.
1 6 Effecti ve  f or ms  of  birt h  c o ntr ol  i ncl u de  a)  h or m o nal   c o ntrace pti ves  [ oral,  i nj ecta ble,  tra ns der mal  or 
i ntra va gi nal] f or o ne f ull c ycl e (e. g., f o ur t o ei g ht  wee ks), or i ntra uteri ne de vice (I U D) f or o ne wee k, f or 
i nj ecta ble  (e. g.,  De p o- Pr o vera)  t he  re q uire me nt  is  at  least  se ve n  da ys  after  i nj ecti o n,  pri or  t o  test  article 
a p plicati o n, or b) c o n d o m a n d s per mici dal, or dia p hra g m/cer vical ca p a n d s per mici dal w hic h are effecti ve 
as  s o o n  as  t he  birt h  c o ntr ol  met h o d  is  a d mi nister e d  pr o perl y.  Ot her  acce pta ble  f or ms  of  birt h  c o ntr ol 
i ncl u de:  a)  a bsti ne nce  f or  s u bj ects  w h o  are  n ot  se x uall y  acti ve  or  b)  if  t he  s u bj ect  is  i n  a  m o n o ga m o us 
relati o ns hi p  wit h  a  part ner  w h o  is  sterile  (e. g.,  a  vasect o m y  perf or me d  at  least  si x  m o nt hs  pri or  t o  t he 
s u bj ect’s  i nitiati o n  of  treat me nt).  S u bj ects  w h o  bec o me  se x uall y  acti ve  or  be gi n  t o  ha ve  relati o ns  wit h  a 
part ner  w h o  is  n ot  sterile  d uri n g  t he  st u d y  m ust  a gree  t o  use  a n  effecti ve  f or m  of  birt h  c o ntr ol  f or  t he 
d urati o n of t he st u d y. 
1 7 W o me n of c hil d beari n g p ote ntial ( W O C B P) ta ki n g h or m o n al t hera p y m ust be o n treat me nt pri or t o st u d y 
e ntr y, c o nti n ue d per la bel, a n d m ust n ot c ha n ge t heir d osi n g re gi me n d uri n g t he st u d y. 
1 8 U P Ts m ust ha ve a mi ni m u m se nsiti vit y of 2 5 mI U ß- h C G/ m L.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 2 of 5 9 
6.  Has t he nee d or pla ns t o be e x p ose d t o ar tificial t a n ni n g d e vices or e x cessi ve s u nli g ht 
d uri n g t he st u d y. 
7. Is  i m m u n os u p presse d  (e. g.,  h u ma n  i m m u n o defici e nc y  vir us,  s yste mic  m ali g na n c y, 
gr aft h ost disease, etc.) or is ta ki n g me dicati o ns t hat s u p press t he i m m u ne s yste m.
8.  Has  e x perie nce d  a n  u ns uccessf ul  o utc o me fr o m  pre vi o us  t o pical  dicl ofe nac  s o di u m 
t hera p y;  a n  u ns uccessf ul  o utc o me  is  defi ne d  as  “after  a  reas o na bl e  t hera pe utic  trial 
wit h n o c o m plia nce iss ues a n d t he t o pical dr u g di d n ot w or k”. 
9.  Has  a  hist or y  of  se nsiti vit y  t o  a n y  of  t he  i n gre die nts  i n  t he  test  articles  i ncl u di n g 
dicl ofe nac,  b e nz yl  al c o h ol,  p ol yet h yle n e  gl yc ol  m o n o met h yl  et her  3 5 9,  h yal ur o n ate 
s o di u m, s o di u m  p h os p hate  m o n o basic  a n h ydr o us,  s o di u m  h y dr o xi de  or  ot her 
e x ci pie nts i n t he test pr o d uct or R L D. 
1 0.  Has  si g ns  or  s y m pt o ms  c o nsiste nt  wit h  t he  as piri n  ( A S A)  tria d:  ast h matic  s u bjects 
w h o  e x perie nce  r hi nitis  wit h  or  wit h o ut nas al  p ol y ps,  or  w h o  e x perie nce  se vere 
br o nc h os pas m aft er ta ki n g as piri n or n o nste r oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds).
1 1.  Use d  t o pical  pr o d uct  ot her  t ha n  t he  assi g n e d  treat me nt  (i ncl u di n g  m oist urizers,  s u n 
scree n,  crea ms,  oi nt me nts, l oti o ns,  p o w ders,  or  gels  an d  ne w  bra n ds  of  ma ke- u p) 
wit hi n t he selecte d treat me nt area wit hi n o ne da y pri or t o t he Bas eli ne Visit.
1 2.  Has  use d  t o pical  me dicati o ns:  c ortic oste r oi ds, al p ha  h y dr o x y  aci ds  (e. g.,  gl yc oli c 
aci d,  lactic  aci d,  et c.  > 5 %),  beta  h y dr o x y  aci d  (salic ylic  aci d  > 2 %),  urea  > 2 %,  5-
fl u or o uracil, di cl ofe nac, i mi q ui m o d, i n ge n ol meb utate, a mi n ole v uli nic aci d ( A L A) or 
prescri pti o n reti n oi ds (e. g., tazar ote n e, a da p al e ne, treti n oi n), o ver-t he-c o u nter ( O T C) 
pr o d ucts  la bele d  as  scr u bs  of  a n y  ki n d  w hi c h  are  use d  t o  s m o ot h  t he  s ki n  (as  t he y 
c o ntai n s o me f or m of e xf olia nt s uc h as n ut s hells, c offee gr o u n ds, p ol y m er particles, 
etc.) wit hi n t he s electe d treat me nt area (face or b al d scal p) wit hi n o ne m o nt h pri or t o 
t he Bas eli ne Visit.
1 3.  Has  ha d  cr y o destr u cti o n  or  c he m o destr u cti o n,  c uretta ge,  p h ot o d y na mic  t hera p y 
( P D T),  s ur gical  e x cisi o n,  or  ot her  treat me nts  f or  A K  wit hi n  t he  selecte d  treat me nt 
area (face or bal d scal p) wit hi n o ne  m o nt h pri or t o t he Bas eli ne Visit.
1 4.  Has  use d  s yste mic  c orti c oster oi d  t hera p y  (i ncl u des  i ntra m usc ular  a n d  i ntra-artic ul ar 
a d mi nistrati o n), i nterfer o n, c yt ot o xic dr u gs, i m m u n o m o d ulat ors, i m m u n os u p pressi ve 
t hera pies, or reti n oi ds wit hi n o ne m o nt h pri or t o t he Bas eli ne Visit.
1 5.  Has use d or al is otreti n oi n wit hi n si x m o nt hs pri or t o t he Baseli ne Visit.
1 6.  Has use d c he mical peels, i ncl u di n g b ut n ot li mite d t o al p ha h y dr o x y aci d, beta h y dr o x y 
aci d,  bic hl or o acetic  aci d,  tric hl or oacetic  aci d,  a n d  p h e n ol  wit hi n  t he  selecte d 
treat me nt ar ea (face or b al d scal p) wit hi n si x m o nt hs pri or t o t he Bas eli ne Visit.
1 7.  Has  ha d  der mat ol o gic  pr oce d ures  or  s ur g eries  s uc h  as:  laser  res urfaci n g,  P U V A 
( Ps orale n  +  ultra vi olet  A)  t hera p y,  ultra vi olet  B  ( U V B)  t hera p y,  or  der ma brasi o n 
wit hi n t he selecte d treat me nt area (face or b al d s cal p) wit hi n si x m o nt hs pri or t o t he 
Baseli ne Visit.
1 8.  Has  lesi o ns  s us pici o us  f or  s ki n  ca n cer  (s ki n  ca ncer  n ot  r ule d  o ut  b y  bi o ps y)  or 
u ntreate d s ki n ca ncers wit hi n t he selecte d treat me nt area (face or b al d scal p).
1 9.  Has  a n y  s ki n pat h ol o g y  or  c o n diti o n  wit hi n  t he  selecte d  treat me nt  area  (t he  face  or 
bal d  scal p)  s u c h  as  at o pic  der matitis,  ecze m a,  ps oriasis,  r osacea,  s u n b ur n,  or  ot her 
c o nf o u n di n g s ki n c o n diti o n(s) t hat, i n t he i n vesti gat or’s o pi ni o n, c o ul d i nterfere wit h 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 3 of 5 9 
t he e val uati o n of t he test article or re q uires t he us e of i nterferi n g t o pical, s yste mic, or 
s ur gical t hera p y.
2 0.  Has acti ve  gastr oi ntesti nal ul cerati o n  or  blee di n g  or  has  a hist or y  of  gastr oi ntesti nal 
blee ds d ue t o use of as piri n or ot her N S AI Ds. 
2 1.  Has se vere r e nal or he patic i m pair me nt.
2 2.  Has  a n y  c o n diti o n  w hic h,  i n  t he  i n vesti g at or’s  o pi ni o n,  w o ul d  ma ke  it  u nsafe  or 
precl u de t he s u bj ect’s a bilit y t o f ull y partici pate i n t his researc h st u d y.
2 3. Is  u na bl e  t o  c o m m u nicate  or  c o o perate  w it h  t he  i n vesti gat or  d ue  t o  la n g ua ge 
pr o ble ms,  p o or  m e ntal  de vel o p me nt,  i m p aire d  cere bral  f u n cti o n,  or  p h ysical 
li mitati o ns.
2 4. Is  k n o w n  t o  be  n o nc o m plia nt  or  is  u nli kel y  t o  c o m pl y  wit h  t he  re q uire me nts  of  t he 
st u d y  pr ot oc ol  (e. g.,  d u e  t o  alc o h olis m,  dru g  de p e n de nc y,  m e ntal  i nca p acit y)  i n  t he 
o pi ni o n of t he i n vesti gat or.  
2 5.  Has bee n pre vi o usl y e nr olle d i n t he sa me st u d y. 
5. 1. 3 
S u bject Wit h dr a w al Criteri a
Pr oce d ures  f or  h a n dli n g  s u bjects  w h o  are  di sc o nti n ue d  fr o m  t he  st u d y  are  descri be d  i n 
Secti o n 1 3. 2 . S u bjects w h o are disc o nti n ue d will n ot be re place d. 
6. 
T E S T A R TI C L E S A N D R E GI M E N
Test article is defi ne d as a p har mace utical f or m of a n acti ve i n gre di e nt or ve hicle/ place b o 
bei n g teste d or use d as refere n ce i n t he st u d y, w het her bli n de d or u n bli n de d. 
6. 1  
Descri pti o n
Refere n ce liste d dr u g:   
Dicl ofe n ac S o di u m Gel, 3 % ( F o u gera) 
Acti ve i n gre die nt:  
  
Dicl ofe nac s o di u m 
Ot her i n gre die nts:  
Be nz yl  alc o h ol,  h y al ur o nate  s o di u m,  p ol yet h yle ne  gl yc ol 
m o n o met h yl et her, a n d p urifie d water. 
Test pr o d uct:    
  
G D C 6 9 5
Acti ve i n gre die nt:  
  
Dicl ofe nac s o di u m 
Ot her i n gre die nts:  
Be nz yl  alc o h ol,  h y al ur o nate  s o di u m,  p ol yet h yle ne  gl yc ol 
m o n o met h yl et her, a n d p urifie d water. 
Place b o:  
  
  
Ve hicle gel 
Acti ve i n gre die nt:  
  
N o ne 
Ot her i n gre die nts:  
Be nz yl  alc o h ol,  h y al ur o nate  s o di u m,  p ol yet h yle ne  gl yc ol 
m o n o met h yl  
et her,  
s o di u m  
p h os p hate  
m o n o basic 
a n h y dr o us, s o di u m h y dr o xi de, a n d p urifie d water. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 4 of 5 9 
6. 2 
I nstr ucti o ns f or Use a n d A p plic ati o n
At Visit 1/ Baseli ne, t he i n vesti gat or will desi g n at e t he 2 5 c m 2 treat me nt area usi n g a pre-
mar ke d 1 c m 2 gri d de d tra ns pare n c y t o create a “s u bject s pecific” te m plat e a n d will ta k e 
p h ot o gra p hs  of  t he  treat me nt  area  p er  t he  i n str u cti o ns  pr o vi de d  i n  t he  Treat me nt  Area 
I d e ntificati o n Ma n ual.
S u bjects will be i nstr ucte d t o a p pl y t he test article t wice dail y, o n ce i n t he m or ni n g a n d 
o nce  i n  t he  e ve ni n g  ( e. g.,  a p pr o xi matel y  8- 1 2  h o urs  a part),  f or  6 0  da ys  t o  t he  e ntire  2 5 
c m 2 treat me nt  ar ea  (t he  face  [e x cl u di n g  t he  ears]  or  t he  b al d  scal p).  Bal d  scal p  f or  t he 
p ur p oses of t his st u d y is a scal p w here t he s u bject has l ost t he maj orit y of t heir hair ( well 
o ver 5 0 %) wit hi n t he i nte n de d 2 5 c m 2 treat me nt area w here t he scal p is: a) rea dil y visi ble 
a n d 2) t he n u m ber of t h e A Ks i n t he treat me nt area ca n be easil y see n a n d c o u nte d b y t h e 
e val uat or.  It  is  als o  i m p orta nt  t hat  b ot h  t he  site  a n d  s u bject  ca n  re peat e dl y  i de ntif y  t he 
treat me nt  area  t o  ass ur e  acc urate  re p eat  t hera p y  b y  t h e  s u bject  a n d  e val uati o n  b y  t h e 
i n vesti gat or. S u bjects will be i nstr ucte d t o use t he p h ot o gra p h a n d t he “s u bject s pecific” 
te m plate  of  t heir  2 5  c m2 treat me nt  area  pr o vi de d  t o  t he m at  Bas eli ne  i n  or der  t o  hel p 
e ns ure  pr o per  a p plicati o n  of  t he  t est  article.  Test  article  ma y  be  a p plie d  wit h  t he 
fi n gerti ps. N or mall y 0. 5 gr a ms of gel is use d o n eac h 2 5 c m2 treat me nt area (e. g., sli g htl y 
s maller t ha n t he size of a di me; see A p pe n di x 1 ) a n d a p plie d as a t hi n fil m t o t he e ntire 
treat me nt  area  a n d  r u b be d  u ntil  t he  gel  is n o  l o n ger  visi ble  as  i nstr ucte d  b y  t h e 
i n vesti gat or  or  site  staff.  I m me diatel y  after  a p pli cati o n,  t he  h a n ds  s h o ul d  be  t h or o u g hl y 
was he d. S u bjects will be ca uti o ne d t o a v oi d a p pl yi n g t he gel near t he e yes, n ostrils, a n d 
m o ut h.  T he  test  article  s h o ul d be  left  o n  t he  s ki n  f or  a  mi ni m u m  of  f o ur  h o urs  pri or  t o 
was hi n g. Treat me nt s h o ul d c o nti n ue f or t he f u ll treat me nt c o urs e e ve n if all A Ks a p pear 
t o be g o ne. T he st u d y st aff s h o ul d de m o nstrate t h e pr o per use of t h e test article usi n g t he 
ve hicle  gel  pr o vi de d  f or s u bject  trai ni n g.  See A p pe n di x  1
f or  t he  c o m plete  S u bject 
I nstr u cti o ns. 
6. 3  
W ar ni n gs, Prec a uti o ns a n d C o ntr ai n dic ati o ns
6. 3. 1  
C o ntr ai n dic ati o ns 
Dicl ofe nac  s o di u m  gel  is  c o ntrai n dicate d  i n  s u bj ects  wit h  a  k n o w n  h y perse nsiti vit y  t o 
dicl ofe nac,  b e nz yl  alc o h ol,  p ol yet h yl e n e  gl yc ol  m o n o met h yl  et her  3 5 0,  a n d/ or 
h yal ur o n ate s o di u m. 
Dicl ofe nac s o di u m gel is c o ntrai n dicate d i n t he f oll o wi n g patie nts:
I n t he s etti n g of c or o n ar y arter y b y p ass graft s ur ger y. 
6. 3. 2  
W ar ni n gs 
As  wit h  ot her  N S AI Ds,  a na p h ylact oi d  reacti o ns  ma y  occ ur  i n  s u bjects  wit h o ut  pri or 
e x p os ure t o dicl ofe n ac. Dicl ofe n ac s o di u m s h o ul d be gi v e n wit h ca uti o n t o s u bjects wit h 
t he as piri n tria d. T he tria d t y picall y occ urs i n ast h matic s u bjects w h o e x perie nce r hi nitis 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 5 of 5 9 
wit h or wit h o ut nasal p ol y ps, or w h o e x hi bit se vere, p ote ntiall y fa tal br o nc h os pas m after 
ta ki n g as piri n or ot h er N S AI Ds. 
6. 3. 3 
Prec a uti o ns
Dicl ofe nac s o di u m gel s h o ul d be use d wit h ca u ti o n i n s u bjects wit h acti ve gastr oi ntesti nal 
ulcerati o n  or  blee di n g  a n d  se vere  re nal  or he patic  i m pair me nts.  Di cl ofe nac  s o di u m  gel 
s h o ul d n ot be a p plie d t o o pe n s ki n w o u n ds, i nfecti o ns, or e xf oliati ve der matitis. It s h o ul d 
n ot be all o we d t o c o me i nt o c o ntact wit h t he e yes. 
T he safet y of t he c o nc o mita nt use of s u nscree ns, c os metics or ot her t o pical me dicati o ns, 
a n d dicl ofe nac s o di u m gel is u n k n o w n. 
Alt h o u g h  l o w,  t her e  is  s yste mic  e x p os ure  t o  dicl ofe nac  f oll o wi n g  l a bele d  use  of 
dicl ofe nac  s o di u m  gel.  T heref ore,  c o nc o mita nt  a d mi nistrati o n  of  dicl ofe nac  s o di u m  gel 
wit h oral N S AI D S or as piri n ma y res ult i n i ncreas e d N S AI D a d v erse effects. 
6. 3. 4  
Ot her C o nsi der ati o ns
T hese test articles ar e f or t o pical us e o nl y ( n ot f or oral, o p ht hal mic, or i ntra va gi nal use). 
C o ntact wit h e yes, li ps, a n d n ostrils s h o ul d be a v oi de d. If c o ntact wit h t he m o ut h or e yes 
occ urs, ri nse t h or o u g hl y wit h water ri g ht a w a y. 
Areas  treate d  wit h  t h e  t est  article  s h o ul d  n ot   b e  c o vere d  wit h  a n y  t y p e  of  ba n d a ge  or 
occl usi ve dressi n gs.
S u bjects wit h a k n o w n se nsiti vit y t o a n y of t he i n gre die nts i n t he test articles s h o ul d n ot 
partici pate i n t his st u d y.
I n case of acci de ntal i n gesti o n, s u bjects s h o ul d c o ntact t he i n vesti gat or i m me diatel y.
T he  effects  of  t he  test  article  i n  n ursi n g   m ot hers,  pre g n a nt  w o me n  a n d  t heir  u n b or n 
c hil dre n are u n k n o w n. W O C B P m ust n ot be pre g n a nt or pla n ni n g a pre g n a nc y d uri n g t he 
st u d y peri o d. 
7.  
R A N D O MI Z A TI O N A S SI G N M E N T
S u bjects w h o are eli gi ble f or e nr oll me nt i nt o  t he st u d y will be ra n d o mize d b y assi g ni n g 
t he l o west s u bject kit n u m ber a vaila bl e at t he site. S u bjects will be ra n d o mize d t o o ne of 
t hree  treat me nts  o n  a  1: 1: 1  basis  [ G D C  6 9 5  ( Ga ge),  Dicl ofe nac  S o di u m  Gel,  3 % 
( F o u gera), or ve hicle gel ( Ga ge), res p ecti vel y].
8. 
P RI O R A N D C O N C O MI T A N T T H E R A PI E S
C urre nt  me dicati o ns  a n d  a n y  me dicati o ns  ta ke n  wit hi n  3 0  da ys  pri or  t o  t he  start  of  t he 
st u d y  ( Scree ni n g/ Bas eli ne,  Visit  1)  will  be  rec or de d  as  pri or/c o nc o mita nt  me dicati o ns 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 6 of 5 9 
wit h  t he  d ose  a n d  c orres p o n di n g  i n dicati o n.  T h e  me dicati o ns  t o  b e  rec or de d  i ncl u d e 
prescri pti o n  a n d  O T C  me dicati o ns  (e x ce pt vita mi ns  a n d  dietar y  s u p ple me nts).  All 
me dicati o ns  ta ke n  o n  a  re g ular  b asis  s h o ul d  be  rec or de d  o n  t his  pa ge  pri or  t o 
c o m me nci n g t he use of t he test article. A n y c h a n ges i n c o nc o mita nt me dicati o ns d uri n g t he 
st u d y m ust be rec or de d o n t he C R Fs. 
T hera pies ( me dicati o n a n d n o n- me dicati o n t hera pie s) n ot restricte d b y t he pr ot oc ol ma y be 
use d d uri n g t he st u d y f or t he treat me nt or pre v e nti o n of disease or t o mai ntai n g o o d healt h. 
Vita mi ns a n d mi neral s u p ple me nts are per mitte d at d osa ges c o nsi dere d b y t he i n vesti gat or 
as reas o na ble f or mai ntai ni n g g o o d healt h. N o n- pr o hi bite d c hr o nic t hera pies bei n g use d at 
Visit 1 ma y be c o nti n ue d. All c o nc o mita nt t h era pies d uri n g t he st u d y m ust be rec or de d o n 
t he C o nc o mita nt T hera p y case re p ort f or m ( C R F). 
T he  reas o n  f or  a n y  c ha n ges  i n  c o nc o mita nt  me di cati o ns  or  t hera pies/ pr o ce d ures  s h o ul d 
be  re p orte d  a n d  s h o ul d  reflec t  eit her  a  baseli ne  me dical c o n diti o n  d oc u me nte d  i n  t he 
me dical hist or y of t he C R F or a n a d v erse e ve nt ( A E).
8. 1 
Pr o hi bite d Me dic at i o ns or T her a pies
Pr o hi bite d me dicati o ns or t hera pies d uri n g t he st u d y i ncl u de: 
T o pical pr o d uct ot her t ha n t he assi g ne d trea t me nt (i ncl u di n g m oist urizers, s u n scree n, 
crea ms, oi nt me nts, l oti o ns, p o w ders, or gels  of a n y ki n d a n d ne w bra n ds of ma ke- u p) 
wit hi n t he selecte d treat me nt area wit hi n o ne da y pri or t o t he Bas eli ne Visit.
T o pical  me dicati o ns:  c ortic oster oi ds,  al p ha  h y dr o x y  aci ds  (e. g.,  gl yc olic  aci d,  lactic 
aci d,  etc.  > 5 %),  bet a  h y dr o x y  aci d  (salic ylic  aci d  > 2 %),  urea  > 2 %,  5-fl u or o uracil, 
dicl ofe nac,  i mi q ui m o d,  i n ge n ol  me b utate, A L A  or  prescri pti o n  reti n oi ds  (e. g., 
tazar ote ne, a da p ale ne, tr eti n oi n), O T C pr o d ucts la bele d as scr u bs of a n y  ki n d w hic h 
are use d t o s m o ot h t he s ki n (as t he y c o ntai n s o me f or m of e xf olia nt s uc h as n ut s hells, 
c offee  gr o u n ds,  p ol y m er  particles,  etc.)  wit hi n  t he  selecte d  treat me nt  area  (face  or 
bal d scal p) wit hi n o ne m o nt h pri or t o t he Bas eli ne Visit.
Cr y o destr u cti o n  or  c h e m o destr ucti o n,  c uretta ge,  P D T,  s ur gical  e x cisi o n,  or  ot her 
treat me nts f or A K wit hi n t he sel ecte d treat me nt area (face or bal d s cal p) wit hi n o ne 
m o nt h pri or t o t he Baseli ne Visit.
S yste mic  c ortic oster oi d  t hera p y  (i ncl u d es  i ntra m usc ular  a d mi nistrati o n,  see Secti o n 
8. 2 f or g ui da nce re gar di n g i ntra-artic ular c ortic oster oi ds), i nterfer o n, c yt ot o xic dr u gs, 
i m m u n o m o d ulat ors,  i m m u n os u p pressi ve  t hera pies,  or  reti n oi ds  wit hi n  o ne  m o nt h 
pri or t o t he Bas eli ne Visit.
Oral is otreti n oi n wit hi n si x m o nt hs pri or t o t he Baseli ne Visit.
C he mical  peels,  i ncl u di n g  b ut  n ot  li mite d  t o  al p ha h y dr o x y  aci d,  b eta h y dr o x y  aci d, 
bic hl or oacetic aci d, tric hl or oacetic aci d, a n d p h e n ol wit hi n t he selecte d treat me nt area 
(face or bal d s cal p) wit hi n si x m o nt hs pri or t o t he Baseli ne Visit.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 7 of 5 9 
Der mat ol o gic pr o ce d ur es or s ur geri es s uc h as: las er res urfaci n g, P U V A t hera p y, U V B 
t hera p y, or der ma brasi o n wit hi n t he selecte d treat me nt area (face or bal d s cal p) wit hi n 
si x m o nt hs pri or t o t he Baseli ne Visit.
Areas treate d wit h t h e test article s h o ul d n ot  be c o vere d wit h a n y t y p e of ba n da ge or 
occl usi ve dressi n gs.
8. 2  
All o w e d Me dic ati o ns or T her a pies
T he use of a n y of t he f oll o wi n g all o we d me di cati o ns or t hera pies s h o ul d b e d oc u me nt e d 
i n t he s u bject’s C R F. 
A n y me dicati o ns n ot i nte n de d or be neficial f o r t he treat me nt of A Ks ma y be use d u nless 
s pecificall y  e xcl u de d  or  pr o hi bite d  b y  t his  pr ot oc ol  (see Secti o n  8. 1 :  Pr o hi bite d 
Me dicati o ns or T hera pies a b o ve). 
N O T E:  I deall y,  treat me nt  of  A Ks  at  a  b o d y  site  e x cl usi ve  of  t he  H E A D  s h o ul d  be 
a v oi de d  d uri n g  t he  st u d y  peri o d u nless t he  treat me nt  is  dee me d  t o  be  a  material 
me dical necessit y f or t he s u bject b y t h e i n vesti gat or. I n s uc h cases, t he O N L Y all o we d 
treat me nts  f or  A Ks,  at  a n y  b o d y  site  e xcl usi ve  of  t he  H E A D,  are  f ocal  a n d  li mite d 
treat me nt t o t he A K site o nl y usi n g s ur gical e xcisi o n, cr y ot hera p y, a n d c uretta ge ± pi n 
p oi nt  f ocal  electr o dessicati o n.  Use  of  a n y  ot her  treat me nt  met h o ds  is  pr o hi bite d  (see 
Secti o n 8. 1 ), as are t he treat me nt of a n y A Ks o n t he H E A D usi n g a n y met h o d.  
I n  t he  e ve nt  t hat  treat me nt  of  a n  A K  o n  t he  H E A D,  b ut  o utsi de  t he  treat me nt  area,  is 
dee me d  necessar y  b y  t he  i n vesti gat or,  s uc h   a  pr oce d ure  ma y  o nl y  be  perf or me d  after 
disc ussi o n a n d t he a p pr o val b y t he Me dical M o nit or.
I ntra nasal, i n hale d, a n d o p ht hal mic c ortic oster oi ds use d f or t he ma na ge me nt of aller gies, 
p ul m o nar y dis or ders, or ot her c o n diti o ns. 
A  si n gle  i ntra-artic ular  c ortic oster oi d  i njecti o n  is all o we d  d uri n g  t he  st u d y.  A d diti o nal 
treat me nts are all o we d o nl y wit h t he a p pr o val of t he Me dical M o nit or.
Pr otecti ve cl ot hi n g (e. g., a hat) is e nc o ura g e d t o re d uce e x p os ure of t he treat me nt area 
t o s u nli g ht.  
Use  of  a  li g ht  b o die d  bla n d  m oist urizer  i n  t h e  treat me nt  area  as  a n  ai d  t o  ma na gi n g 
l ocal  s ki n  reacti o ns  is  all o we d  O N L Y  wit h  t he  a p pr o val  of  t he  M e dical  M o nit or. 
E x a m ples  of  li g ht  b o die d  m oist urizers  are  Ceta p hil,  L u bri der m  ( wit h o ut  al p ha 
h y dr o x y  aci d),  a n d  ot her  bla n d  m oist urize rs  t hat  d o  n ot  c o ntai n  a n y  “acti ve” 
i n gre di e nts (e. g., s alic yli c aci d, lactic aci d, p yr u vi c aci d, urea, or a n y ot h er i n gre die nt 
t hat  c o ul d  irritate  or  ca use  a  k erat ol ytic effect).  M oist urizers  s h o ul d  n ot  be  a p plie d 
wit hi n  f o ur  ( 4)  h o urs  aft er  test  article  a p plicati o n.    N O T E:  m oist urizers,  if  all o we d 
a n d use d i n t he treat me nt area, s h all be rec or d e d as a c o nc o mita nt t hera p y. 
9. 
S T U D Y P R O C E D U R E S
S pecific acti vities f or eac h st u d y visit are liste d bel o w.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 8 of 5 9 
9. 1  
Visit 1 (- 3 0 t o D a y 1): Scree ni n g/ B aseli ne 
I nf or me d c o ns e nt ma y b e c ollecte d  fr o m st u dy s u bjects u p t o 3 0 da ys b ef ore Visit 1.  If 
a p plica ble, q ualifie d s u bjects ca n was h o ut fr o m pr o hi bite d me dicati o ns or treat me nts (see 
Secti o n  8. 1 )  pri or  t o  t heir  Scree ni n g/ Baseli ne  Visit  o nce  i nf or me d  c o nse nt  has  bee n 
o btai ne d.  If w as h o ut peri o d e x cee ds 3 0 da ys, re-c o nse nt is re q uire d. T he  Scree ni n g a n d 
Baseli ne Visit ma y be c o m plete d o n t he sa me da y, if n o was h o ut is re q uire d. 
At t his visit, t he i n vesti gat or or desi g nee will:
O btai n a si g ne d, writte n i nf or me d c o nse nt, a n d u p date t he S u bject Scree ni n g a n d 
E nr oll me nt L o g.
C o nfir m t he s u bject meets t he i ncl usi o n/e x cl usi o n criteria.
D oc u me nt t he i nf or mati o n re q uire d o n t he M e dical Hist or y f or m. 
D oc u me nt t he i nf or mati o n re q ui re d o n t he De m o gra p hics f or m. 
Rec or d  
t he  
s u bject’s  
pri or  
a n d/ or  
c o nc o mita nt  
me dicati o ns  
a n d 
t hera pies/ pr oce d ur es.  
If  t he  s u bject  re q uires  w as h o ut  fr o m  pre vi o us  me dicati o ns,  t he  re mai ni n g  acti vities 
will be perf or me d aft er was h o ut  is c o m plete d a n d m ust be c o m plete d wit hi n 3 0 da ys 
of first visit, or t he s u bject nee ds t o be re-c o ns e nt e d. 
Perf or m  a  d er mat ol o gic  e x a m.  C o nsis te nt  wit h  E x cl usi o n  Criteri o n  # 1 8, a n y 
s u bject wit h a s us pici o us lesi o n wit hi n t he treat m e nt area s h o ul d n ot be e nr olle d 
pri or t o c o nfir m ati o n t hat t he lesi o n is n ot s ki n ca n cer. I n t he e ve nt t hat a bi o ps y is 
warr a nte d t o ma ke s uc h a deter mi nati o n pe r t he i n vesti gat or, s uc h a pr oce d ure is 
c o nsi dere d o utsi de t h e sc o pe of t his st u d y a n d t heref ore will be t he res p o nsi bilit y 
of t he p ote ntial s u bject. I n t he e ve nt t hat a bi o ps y is nee de d a n d it is n ot a v aila ble 
f or re vie w, t he s u bject s h all be c o nsi dere d a scree n fail ure.
I d e ntif y  t he  2 5  c m2 treat me nt  area  o n  eit her  t he  face  (e x cl u di n g  ears)  or  bal d 
scal p. N O T E: Use t he pr oce d ure as d etaile d i n t h e Treat me nt Area I d e ntificati o n 
Ma n ual  t o  create  a n d  la bel  t he  tra ns pare nc y  t o  rec or d  t he  desi g nate d  treat me nt 
area.
Create a “s u bj ect s pecifi c” te m plate per t he i nstr ucti o ns pr o vi de d i n t he Treat me nt 
Area  I d e ntificati o n  Ma n ual  t o  assist  t he  s u bject  i n  t he  i de ntificati o n  of  t he 
treat me nt ar ea pri or t o a p plicati o n of t he test arti cle. A c o p y of t he te m pl ate will 
als o be ret ai ne d i n t he s u bject’s site file f or use b y t he site t o pr o perl y i d e ntif y t he 
treat me nt ar ea at f ut ure visits.
Ta ke  Baseli ne  p h ot o gra p hs  of  t he  desi g nate d  2 5  c m 2 treat me nt  area  per  t he 
i nstr ucti o ns  pr o vi de d  i n t he  Treat me nt Area  I d e ntificati o n  Ma n ual  a n d  st ore  o ne 
p h ot o i n t he s u bject’s fil e at t he site a n d gi ve o ne p h ot o t o t he s u bject i n or der t o 
hel p e ns ure pr o per a p plicati o n of t he test article b y t he s u bject. 
Rec or d t he size of t he desi g nate d treat me nt area.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 2 9 of 5 9 
Perf or m  t he  A K  lesi o n  c o u nt  as  descri be d  i n S ecti o n  1 0. 1 ,  w hic h  i ncl u des  a n y 
A Ks ≥4 m m i n dia meter, as well as a n y s maller lesi o ns. N O T E:  A  mi ni m u m  of 
fi ve t o a ma xi m u m of 1 0 A Ks ≥4 m m i n dia meter i n t he 2 5 c m2 treat me nt area is 
re q uire d t o q ualif y. 
D oc u me nt t he dia meter of eac h A K lesi o n i n t he treat me nt area.
Perf or m t he L S R assess me nt as descri be d i n Secti o n 1 0. 2 .
Reaffir m t he I n cl usi o n/ E x cl usi o n criteria.
Perf or m  a  U P T  f or  all  W O C B P.  T he  U P T  m ust  be  ne gati ve  f or  s u bjects  t o 
c o nti n ue. 
Assi g n t he s u bject t he ne xt a vaila ble (l o w est) s u bject n u m ber i n as ce n di n g or der. 
Assi g n  t he  s u bject  t he  l o west  a vaila ble  t est  article  kit  n u m ber  a n d  dis pe nse  test 
article.  N O T E:  Test  arti cle  will  be  wei g h e d  pri or  t o  bei n g  dis pe nse d  a n d  t he 
s u bject will be i nstr ucte d n ot t o o pe n st u d y s u p plies at t he site. 
Re vie w a n d dis pe nse a S u bject I nstr ucti o n S heet t o t he s u bject (see A p p e n di x 1 ). 
I nstr u ct t he s u bject t o a p pl y test article t wice dail y, o n ce i n t he m or ni n g a n d o nce 
i n  t he  e ve ni n g,  a n d  de m o nstrate  pr o per  test  article  a p plicatio n  usi n g  ve hi cle  gel 
pr o vi de d f or s u bject trai ni n g. 
E x plai n a n d iss ue t he s u bject diar y. 
C o nfir m t he ne xt a p p oi nt me nt. 
9. 2  
Visit 2 ( D a y 1 5 ± 3 d a ys): P h o ne C all 
At t his visit, t he i n vesti gat or or desi g nee will:
Q uer y  t h e  s u bject  a b o ut  a n y  c ha n ges  i n  h ealt h  stat us  or  a n y  A Es  si nce  t he  last 
visit.  D oc u me nt  i n  t he  A E  secti o n  of t h e  C R F,  as  a p pr o pri ate.  N O T E:  If  se vere 
t olera bilit y iss ues or a m aterial A E c o n cer n of a n y t y p e are n ote d, t h e s u bj ect ma y 
be sc he d ule d f or a n i n- office vis it at t he i n vesti gat or’s discreti o n.
Rec or d  a n y  c ha n ges  i n  t he  s u bject’s  c o nc o mita nt  me dicati o ns  a n d  t h era pies/ 
pr oce d ur es. 
Re vie w t he s u bject diar y a n d test article c o m plia n ce. 
Re mi n d  t he  s u bject  t o  c o nti n ue  t o  a p pl y  t est  article  t wice  d ail y,  o n ce  i n  t he 
m or ni n g a n d o nce i n t he e ve ni n g, t o t he s ki n of t he 2 5 c m 2 treat me nt area u ntil t he 
ne xt cli nic visit a n d t o bri n g t heir t u be of t est article wit h t he m t o t heir n e xt cli nic 
visit.
C o nfir m  t he  ne xt  a p p oi nt me nt  a n d  i nstr uct  s u bject  t o  n ot  a p pl y  t he  st u d y 
me dicati o n t o t he treat me nt area pri or t o a n y st u d y visits.
9. 3  
Visit 3 ( D a y 3 0 ± 3 d a ys): F oll o w- U p
At t his visit, t he i n vesti gat or or desi g nee will:
Q uer y  t h e  s u bject  a b o ut  a n y  c ha n ges  i n  h ealt h  stat us  or  a n y  A Es  si nce  t he  last 
visit. D oc u me nt i n t he A E sec ti o n of t he C R F, as a p pr o priate. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 0 of 5 9 
Rec or d  a n y  c ha n ges  i n  t he  s u bject’s  c o nc o mita nt  me dicati o ns  a n d  t h era pies/ 
pr oce d ur es. 
Use  t he  tra ns par e nc y  a n d  t he  Baseli ne  p h ot o  as  necessar y  t o  l ocat e  t he  selecte d 
treat me nt ar ea.
Perf or m t he L S R assess me nt as descri be d i n Secti o n 1 0. 2 .
Re vie w/c ollect/ distri b ute t he s u bject diar y as n ecessar y.
Re vie w  test  article  c o m plia nce.  T est  articl e  a p plicati o n  will  be  de m o nstrate d  if 
dee me d  necessar y.  As  n ecessar y,  t he  Baseli ne  p h ot o gra p h  a n d  t he  te m plate  ma y 
be  use d  as  a  vis ual  ai d  t o  re-i nstr uct  s u bject  o n  pr o per  a p plicati o n  of  t he  test 
article t o t he treat me nt area.
T he s u bject’s t u be of t est article will be wei g h e d a n d re- dis pe nse d. 
Re mi n d  t he  s u bject  t o  c o nti n ue  t o  a p pl y  t est  article  t wice  d ail y,  o n ce  i n  t he 
m or ni n g a n d o nce i n t he e ve ni n g, t o t he s ki n of t he 2 5 c m 2 treat me nt area u ntil t he 
ne xt cli nic visit.
C o nfir m t he ne xt a p p oi nt me nt. 
9. 4  
Visit 4 ( D a y 4 5 ± 3 d a ys): P h o ne C all 
At t his visit, t he i n vesti gat or or desi g nee will:
Q uer y  t h e  s u bject  a b o ut  a n y  c ha n ges  i n  h ealt h  stat us  or  a n y  A Es  si nce  t he  last 
visit.  D oc u me nt  i n  t he  A E  secti o n  of t h e  C R F,  as  a p pr o pri ate.  N O T E:  If  se vere 
t olera bilit y iss ues or a m aterial A E c o n cer n of a n y t y p e are n ote d, t h e s u bj ect ma y 
be sc he d ule d f or a n i n- office vis it at t he i n vesti gat or’s discreti o n.
Rec or d  a n y  c ha n ges  i n  t he  s u bject’s  c o nc o mita nt  me dicati o ns  a n d  t h era pies/ 
pr oce d ur es. 
Re vie w t he s u bject diar y a n d test article c o m plia n ce. 
Re mi n d  t he  s u bject  t o  c o nti n ue  t o  a p pl y  t est  article  t wice  d ail y,  o n ce  i n  t he 
m or ni n g a n d o nce i n t he e ve ni n g, t o t he s ki n of t he 2 5 c m 2 treat me nt area u ntil t he 
ne xt cli nic visit a n d t o bri n g t heir t u be of t est article wit h t he m t o t heir n e xt cli nic 
visit.
C o nfir m  t he  ne xt  a p p oi nt me nt  a n d  i nstr uct  s u bject  t o  n ot  a p pl y  t he  st u d y 
me dicati o n t o t he treat me nt area pri or t o a n y st u d y visits.
9. 5  
Visit 5 ( D a y 6 0 + 4 d a ys): E n d of Tre at me nt 
At t his visit, t he i n vesti gat or or desi g nee will:
Q uer y  t h e  s u bject  a b o ut  a n y  c ha n ges  i n  h ealt h  stat us  or  a n y  A Es  si nce  t he  last 
visit. D oc u me nt i n t he A E sec ti o n of t he C R F, as a p pr o priate. 
Rec or d  a n y  c ha n ges  i n  t he  s u bject’s  c o nc o mita nt  me dicati o ns  a n d  t h era pies/ 
pr oce d ur es. 
Use  t he  tra ns par e nc y  a n d  t he  Baseli ne  p h ot o  as  necessar y  t o  l ocat e  t he  selecte d 
treat me nt ar ea. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 1 of 5 9 
Perf or m  t he  A K  lesi o n  c o u nt  as  descri be d  i n S ecti o n  1 0. 1 ,  w hic h  i ncl u des  a n y 
A Ks ≥4 m m i n dia meter, as we ll as a n y s maller lesi o ns.
Perf or m t he L S R assess me nt as descri be d i n Secti o n 1 0. 2 .
Re vie w a n d c ollect t he s u bject diar y a n d test article c o m plia nce. 
T he s u bject’s t u be of t est article will be wei g h e d a n d c ollecte d.
Perf or m a U P T f or all W O C B P.
C o nfir m t he ne xt a p p oi nt me nt. 
9. 6  
Visit 6 ( D a y 9 0 ± 4 d a ys): E n d of St u d y 
At t his visit, t he i n vesti gat or or desi g nee will:
Q uer y  t h e  s u bject  a b o ut  a n y  c ha n ges  i n  h ealt h  stat us  or  a n y  A Es  si nce  t he  last 
visit. D oc u me nt i n t he A E sec ti o n of t he C R F, as a p pr o priate. 
Rec or d  a n y  c ha n ges  i n  t he  s u bject’s  c o nc o mita nt  me dicati o ns  a n d t h era pies/ 
pr oce d ur es. 
Use  t he  tra ns par e nc y  a n d  t he  Baseli ne  p h ot o  as  necessar y  t o  l ocat e  t he  selecte d 
treat me nt ar ea.
Perf or m  t he  A K  lesi o n  c o u nt  as  descri be d  i n S ecti o n  1 0. 1 ,  w hic h  i ncl u des  a n y 
A Ks ≥4 m m i n dia meter, as well as a n y s maller lesi o ns.
Perf or m t he L S R assess me nt as descri be d i n Secti o n 1 0. 2 .
Disc har ge t h e s u bject fr o m t he st u d y.
9. 7  
U nsc he d ule d Visit
T he i n vesti gat or ma y see t he s u bject at a n u nsc h e d ule d visit t o ma na ge a n y A Es or L S Rs. 
At t his visit, t he i n vesti gat or or desi g nee will:
Q uer y  t h e  s u bject  a b o ut  a n y  c ha n ges  i n  h ealt h  stat us  or  a n y  A Es  si nce  t he  last 
visit. D oc u me nt i n t he A E sec ti o n of t he C R F, as a p pr o priate. 
Use  t he  tra ns par e nc y  a n d  t he  Baseli ne  p h ot o  as  necessar y  t o  l ocat e  t he  selecte d 
treat me nt ar ea.
Perf or m t he L S R assess me nt as descri be d i n Secti o n 1 0. 2 .
Rec or d a n y c ha n ges i n t h e s u bject’s c o n c o mita nt me dicati o ns.
Re vie w  s u bject  diar y  a n d  t he  re q uire me nts  f or  test  article  a p plicati o n,  if 
a p plica ble. 
C o nfir m t he ne xt a p p oi nt me nt.  
1 0.  
C LI NI C A L E V A L U A TI O N S
T he f oll o wi n g cli nical e v al uati o ns will be p erf or m e d acc or di n g t o t he sc h e d ules i n dicate d 
d uri n g  t he  st u d y.  T h e  sa me  i n vesti gat or  s h o ul d  c o m plete  t he  e val uati o ns  f or  a  gi ve n 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 2 of 5 9 
s u bject  t hr o u g h o ut  t he  st u d y.  If  t his  bec o m es  i m p ossi ble  a  s u b-i n vesti gat or  wit h 
o verla p pi n g e x perie nce wit h t he s u bject a n d t he st u d y s h o ul d c o m plete t he e val uati o ns. 
1 0. 1  
Acti nic Ker at os es Lesi o n C o u nts
A K lesi o ns will be c o u nt e d at Baseli ne, Da y 6 0/ E O T, a n d D a y 9 0/ E O S. At t he Bas eli ne 
Visit ( Visit 1), all A K lesi o ns i n t he 2 5 c m 2 treat me nt area, i n de pe n de nt of size, will be 
i de ntifie d,  c o u nte d,  a n d  rec or d e d  o n  t he  tra ns pare nc y. T he  n u m ber  a n d  l ocati o n  of  A K 
lesi o ns t o be treate d t h at are 4 m m i n dia meter a n d t he dia met er of eac h A K lesi o n i n t he 
2 5  c m 2 treat me nt  area  will  als o  be  d oc u me nte d  at  t he  Baseli ne  Visit.  T he  s u g geste d 
pr oce d ure f or A K c o u nti n g a n d d efi niti o n of fa ce (e x cl u di n g ears) a n d b al d scal p will be 
detaile d  i n  a  s e parate  d o c u me nt.  At  t he  Bas eli ne  Visit,  t he  2 5  c m 2 treat me nt  area  m ust 
i ncl u de at least fi ve a n d n o m ore t ha n 1 0 cli nicall y t y pi cal, visi ble, or pal pa ble, discrete, 
n o n h y per ker at otic,  n o n h y p ertr o p hic,  A K  lesi o n s,  eac h  at  least  4  m m  i n  dia meter, 
c o ntai ne d wit hi n a c o nti n u o us 2 5 c m 2 treat me nt area l ocate d o n t he face (e x cl u di n g ears) 
or bal d scal p. At t he E O T a n d E O S visits, t h e n u m ber of t otal A K lesi o ns i n t he 2 5 c m 2 
treat me nt area will be c o u nte d a n d t he n u m ber of ne w A Ks will be i de ntifie d. A ne w A K 
is defi ne d as a lesi o n t hat was n ot prese nt at t he Baseli ne Visit.
N O T E:  T o  e ns ure  acc urate  i de ntificati o n  of  t he  treat me nt  area,  t he  site  m ust  use  t he 
tra ns pare n c y a n d t he Baseli ne p h ot o as necessar y t o l ocate t he selecte d treat me nt area.
If  t he  s u bject  has  a  L S R  t hat  pre ve nts  t he i n vesti gat or  or  desi g nee  fr o m  perf or mi n g  t he 
A K c o u nt at a visit, t he i n vesti gat or or de si g n ee s h o ul d d oc u me nt i n t he s o urce d oc u m e nt 
a n d C R F t hat t he A K c o u nt was u na ble t o be o btai ne d d ue t o a L S R. 
1 0. 2 
L oc al S ki n Re acti o n Assess me nt
At  Baseli ne,  Da y  3 0  f oll o w- u p,  Da y  6 0/ E O T, Da y  9 0/ E O S,  a n d  U nsc he d ule d  Visits  (if 
a p plica ble), t h e i n vesti gat or or desi g nee will ass ess t he 2 5 c m 2 treat me nt area a n d rat e o n 
a  scale  of  0 = a bse nt,  1 = mil d  (sli g ht,  barel y  p erce pti ble),  2 = m o d erate  ( disti nct 
prese nce), a n d 3 = se v ere ( mar ke d, i nte nse) t he f oll o wi n g L S Rs:  
Er yt h e ma
Dr y ness/fla ki n g/scali n g
B ur ni n g/sti n gi n g
Er osi o n/ ulcerati o n 
E de ma
Pai n ( wit hi n t he last 2 4 h o urs) 
Pr urit us (itc hi n g) ( wit hi n t he last 2 4 h o urs) 
T hese  L S Rs  will  be  c oll ecte d  i n de p e n de ntl y  of  A Es.  A n y  L S R  t hat  o cc urs wit hi n  t he 
2 5 c m 2 tre at me nt  are a  (f ace  [e xcl u di n g  t he  e ars]  o r  b al d  sc al p)  a n d  e xte n ds  t o 
a dj ace nt  s urr o u n di n g  s ki n  ( defi ne d  t o  be  u p  t o  a  5  c m  b or der  ar o u n d  t he  2 5  c m 2 
tre at me nt  are a) will  b e  c o nsi dere d  L S Rs.  L S Rs  t hat  re q uire  me dical  i nter ve nti o n 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 3 of 5 9 
( prescri pti o n  me dicati o n)  or  e xte n d  bey o n d  t h e  5  c m  s urr o u n di n g  s ki n  s h o ul d  be 
d oc u me nte d as a n A E. 
1 1. 
P H O T O G R A P H Y
P h ot o gra p h y  d o c u me ntati o n  is  re q uire d  i n  t his st u d y.  P h ot o gra p hs  ta ke n  as  part  of  t his 
st u d y will be us e d t o d oc u me nt pr o per i d e ntificati o n of t he treat me nt area t o hel p e ns ure 
pr o per  a p plicati o n  of  t he  test  article  b y  t h e  s u bject.  P h ot o gra p hs  ma y  als o  be  use d  t o 
d oc u me nt t he effects of treat me nt, A Es, or ot her fi n di n gs d uri n g t he st u d y. T he site will 
be pr o vi de d wit h s u g gest e d g ui d eli nes t o assi st t he m i n ta ki n g sta n d ar dize d p h ot o gra p hs. 
All p h ot o gr a p hs ta k e n as part of t his st u d y are  f or  i nf or mati o nal  p ur p oses  o nl y  a n d  are 
n ot t o assist i n gra di n g or f or a n y ot her assess me nt. 
N ote: S u bjects w h o decli ne t o ha ve Baseli ne p h ot o gra p hs ta ke n will n ot b e eli gi ble t o b e 
i n t he st u d y. A d diti o nal details re gar di n g ta ki n g Baseli ne p h ot o gra p hs are pr o vi de d i n a 
se parat e p h ot o g ui d e (i.e., t he Treat me nt Area I de ntificati o n Ma n ual) pr o vi de d t o t he site. 
1 2. 
L A B O R A T O R Y T E S T S
1 2. 1  
Uri ne Pre g n a nc y Tests
U P Ts  m ust  be  perf or me d  o n  all  W O C B P  at  Bas eli ne  pri or  t o  ra n d o mizati o n  a n d  at  t he 
Da y 6 0/ E O T visit. All W O C B P m ust ha ve a ne gati ve U P T at Baseli ne t o be eli gi ble f or 
st u d y  e ntr y.  T he  U P Ts  will  be  perf or me d  at  t he  st u d y  site,  if  t he  site  is  re gistere d  a n d 
c o nf or ms t o C LI A re g ulati o ns f or s uc h testi n g ( p ossesses a c urre nt v ali d C LI A Certificate 
of  Wai ver),  or  at  a n  a p pr o priatel y  re gistere d  refere nce  l a b orat or y.  T he  i n vesti gat or  will 
re p ort t he U P T res ults o n t he C R Fs, i n t he s u bject’s me dical rec or ds, a n d i n i n de pe n d e nt 
rec or ds mai ntai n e d at t h e st u d y site. T he U P T use d m ust ha ve a mi ni m u m se nsiti vit y of 
2 5 mI U of - h C G/ m L.
1 3. 
E N D O F S T U D Y C RI T E RI A 
At t he e n d of eac h s u bject’s partici pati o n i n t he st u d y, t he i n vesti gat or will c o m plete a n 
E n d of St u d y f or m f or all c o m ple te d a n d disc o nti n ue d s u bjects.  
1 3. 1  
C o m pleti o n of t he St u d y
S u bjects w h o c o m plete t he 6 0- d a y treat me nt a n d all of t he E O S visit e v al uati o ns at D a y 
9 0 will be c o nsi dere d t o ha ve c o m plete d t h e st u d y. 
1 3. 2 
S u bject Disc o nti n u ati o n
A s u bject ma y be wit h dra w n fr o m t he st u d y pr i or t o c o m pleti o n f or a n y of t he f oll o wi n g 
reas o ns:
A Es
Deat h

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 4 of 5 9 
Lac k of efficac y
L ost t o f oll o w- u p 
N o nc o m plia nce wit h st u d y dr u g 
P h ysicia n decisi o n
Pre g n a nc y (if a p plica ble)
Pr o gr essi ve disease
Pr ot oc ol de viati o n 
St u d y t er mi nate d b y S p o ns or 
Wit h dra wal b y s u bject; N O T E: if t he s u bject deci des t o wit h dra w fr o m t he st u d y 
d ue t o a n A E t he n it s h o ul d be classifie d as wit h dra wal d ue t o a n A E. 
Ot her  ( e. g.,  a n y  reas o n  t hat  ma y  affect  t he  o utc o me  of  t he  st u d y  or  s afet y  of 
s u bjects)
If  a  s u bj ect  wit h dra ws  pre mat urel y  f or  a n y  reas o n,  t he  site  s h o ul d  ma ke  e ver y  eff ort  t o 
ha ve  t he  s u bject  ret ur n  f or;  a)  t heir  ne xt sc he d ule d  visit  t o  perf or m  all  re q uire d  visit 
acti vities a n d t o c ollect a n d rec o ncile all test articl e A N D b) re t ur n f or t he E O S visit ( Da y 
9 0) t o perf or m all re q uire d visit acti vities a n d c o m plete t he E O S C R F. If t he s u bject will 
n ot a gree t o ret ur n f or t h e E O S visit, t he site s h o ul d c o m plete t he E O S C R Fs d uri n g t he 
last visit t hat t he s u bject will c o m plete. S u bjects w h o wit h dra w pre mat urel y will n ot be 
re place d. W he n a s u bject is wit h dra w n fr o m t he st u d y f or a treat me nt-relat e d A E (i.e., as 
defi ne d i n Secti o n 1 4 ), w he n p ossi ble, t he s u bject s h o ul d be f oll o w e d u ntil res ol uti o n or 
sta bilizati o n of t he A E. If a s u bject is disc o nti n ue d fr o m t he st u d y d ue t o pre g na nc y, t he 
pre g na nc y a n d its o utc o me s h o ul d be f oll o we d (s ee Secti o n 1 4. 5 ).
1 3. 3 
St u d y Ter mi n ati o n
T he st u d y ma y be t er mi nate d b y t h e i n vesti gat or or t he S p o ns or. If, i n t he o pi ni o n of t he 
i n vesti gat or, cli nical o bs er vati o ns ma de d uri n g t h e st u d y s u g gest t hat it ma y be u n wise t o
c o nti n ue, he or s he ma y st o p t he st u d y. A st u d y ter mi nati o n b y t he i n vesti gat or will be 
re p orte d t o t he S p o ns or. 
I n  a d diti o n,  a  writte n  st ate me nt  f ull y  d o c u me nti n g  t h e  reas o ns  f or  t his  acti o n  will  b e 
s u b mitte d t o t he S p o ns or b y t he i n vesti gat or wit hi n fi ve w or ki n g da ys. 
I n t h e e ve nt t hat t he S p o ns or c h o oses t o disco nti n ue or ter mi nate t h e st u d y, a p pr o priat e 
n otificati o n will be gi ve n t o t he i n vesti gat or.
1 4.  
A D V E R S E E V E N T R E P O R TI N G
1 4. 1  
A d verse E ve nt D efi niti o ns
A n a d verse e ve nt is a n y u nt o war d me di cal occ urre nce ass oci ate d wit h t he use of a dr u g 
i n h u ma ns, w het her or n ot c o nsi dere d dr u g relate d. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 5 of 5 9 
A n A E (als o referre d t o as a n a d vers e e x pe rie nce) ca n be a n y u nfa v ora ble a n d u ni nte n de d 
si g n  (e. g.,  a n  a b n or mal  la b orat or y  fi n di n g), s y m pt o m,  or  disease  te m p orall y  ass ociat e d 
wit h t he use of a dr u g, a n d d oes n ot i m pl y a n y j u d g me nt a b o ut ca usalit y. A n A E ca n arise 
wit h a n y use of t he dr u g (e. g., off-l a bel use, use i n c o m bi nati o n wit h a n y dr u g) a n d wit h 
a n y r o ute of a d mi nistrati o n, f or m ula ti o n, or d ose, i ncl u di n g a n o v er d ose.
S us pecte d a d verse re acti o n is a n y A E f or w hic h t here is a reas o n a ble p ossi bilit y t hat t he 
dr u g ca use d t he A E. “ R eas o na ble p ossi bilit y” mea ns t here is e vi de nce t o s u g gest a ca usal 
relati o ns hi p bet wee n t he dr u g a n d t he A E. A s us pecte d a d verse reacti o n i m plies a lesser 
de gree of certai nt y a b o ut ca usalit y t ha n a d v erse reacti o n, w hic h mea ns a n y A E ca use d b y 
a dr u g.
A n a d verse re acti o n is a n y A E ca use d b y  a dr u g. A d verse reacti o ns are a s u bset of all 
s us pecte d a d v erse reacti o ns f or w hi c h t here is reas o n t o c o ncl u de t hat t he dr u g ca us e d t he 
e ve nt. F or t he p ur p oses of prescri pti o n dr u g l a beli n g, t he ter m a d verse reacti o n is defi ne d 
t o  mea n  “a n  u n desira ble  effect, reas o n a bl y  ass o ciate d  wit h  t he  use  of  a  dr u g  t hat  ma y 
occ ur  as  p art  of  t he  p har mac ol o gical  acti o n  or  ma y  b e  u n pre dict a ble  i n  its  occ urre n ce. 
T his defi niti o n d oes n ot i ncl u de all A Es o bs er ve d d uri n g use of a dr u g,  o nl y t h ose A Es 
f or w hic h t her e is s o me basis t o belie ve t here is  a ca usal relati o ns hi p bet wee n t he dr u g 
a n d t he occ urre n ce of t h e A E”.
A n A E or s us pecte d a d verse reacti o n is c o nsi dere d “ u ne x pecte d” if it is n ot liste d i n t he 
R L D pac k a ge i nsert or is n ot liste d at t h e s pecifi cit y or s e verit y t hat has bee n o bs er ve d. 
F or  e x a m ple,  u n der  t his  defi niti o n,  he patic  ne cr osis  w o ul d  be  u ne x pecte d  ( b y  virt ue  of 
gr eater se verit y) if t he R L D pac ka ge i nsert referre d o nl y t o ele vate d h e patic e nz y m es or 
he patitis.  Si milarl y,  cere bral  t hr o m b oe m b olis m  a n d  cere bral  v asc ulitis  w o ul d  be 
u ne x pecte d  ( b y  virt u e  of  greater  s pecifi cit y)  if  t he  R L D  pac k a ge  i ns ert  liste d  o nl y 
cere bral vas c ular acci d e nts. " U ne x pecte d," as us e d  i n t his defi niti o n, als o refers t o A Es or 
s us pecte d  a d v erse  reacti o ns  t hat  are  me nti o ne d  i n  t he  R L D  pac ka ge  i nsert  as  occ urri n g 
wit h a class of dr u gs or  as a ntici pate d fr o m t he  p har mac ol o gical pr o perti es of t he dr u g, 
b ut  are  n ot  s pecificall y  me n ti o ne d  as  occ urri n g  wit h  t he  partic ular  dr u g  u n der 
i n vesti gati o n.
Ti mel y  a n d  c o m plete  re p orti n g  of  all  A Es  assists 
  i n  i de ntif yi n g 
a n y u nt o w ar d me dical occ urre n ce, t here b y all o wi n g: 
1) 
pr otecti o n of t he safet y of st u d y s u bjects;  
2) 
a great er u n dersta n di n g of t he o verall safet y pr ofile of t he test articl e; 
3) 
rec o g niti o n of d ose-relat e d test article t o xicit y;
4) 
a p pr o priate m o dificati o n of st u d y pr ot o c ols;  
5) 
i m pr o ve me nts i n st u d y d esi g n or pr oce d ures; a n d  
6) 
a d here n ce t o w orl d wi de re g ul at or y re q uire me nts. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 6 of 5 9 
1 4. 2  
A d verse E ve nt D et ails
A Es ma y be eit her s p o nt a ne o usl y re p ort e d or elicite d d uri n g q uesti o ni n g a n d e x a mi nati o n 
of a s u bject. All A Es m ust be rec or d e d o n t h e A E C R F. If k n o w n, t he i n vesti gat or s h o ul d 
re p ort  t he  dia g n osis  of  t he  u n derl yi n g  ill ness  or  dis or der,  rat her  t ha n  its  i n di vi d ual 
s y m pt o ms.  S u bjects  e x perie nci n g  A Es  t hat  ca us e  i nterr u pti o n  or  disc o nti n uati o n  of  test 
article or t h ose e x perie n ci n g A Es t hat are pres e nt at t he e n d of t heir p arti ci pati o n i n t he 
st u d y  s h o ul d  recei ve  f oll o w- u p  as  a p pr o priate. A Es s h o ul d be f oll o we d t o res ol uti o n or 
sta bilizati o n (if p ossi ble) a n d, if t he y b ec o me seri o us, re p orte d as seri o us a d verse e ve nts 
( S A Es,  see Secti o n  1 4. 3 ).  If  p ossi ble,  t h e  o utc o me  of  a n y  A Es  t hat  ca use d  per ma n e nt 
disc o nti n uati o n or t hat were pres e nt at t he e n d of t he st u d y, es peciall y t h ose c o nsi dere d 
b y t he i n vesti gat or t o b e relate d t o t he test article, s h o ul d be re p orte d. 
I nf or mati o n  o n  t he  me di cal  c o n diti o n  of  su bjects  s h o ul d  be gi n f oll o wi n g  t he  s u bject’s 
writte n  c o nse nt  t o  p arti ci pate  i n  t he  st u d y  a n d  a  me dical  hist or y  s h o ul d  be  ta ke n  at 
scree ni n g.  D uri n g  a n y  was h  o ut  a n d  baseli ne  peri o ds,  a n y  c h a n ges  i n  t he  healt h  of 
s u bjects s h o ul d be r ec or de d as c ha n ges i n medical hist or y u nl ess a n e ve nt occ urre d as a 
res ult of a st u d y-rel ate d pr oce d ure a n d is u na ntici p ate d; i n s uc h cases, t he e ve nt s h o ul d be 
rec or d e d  as  a n  A E  a n d  re p orte d  t o  t he  I nstit uti o nal  Re vie w  B oar d  (I R B)  as  a n 
“ u na ntici pate d  pr o ble m”  i n  acc or da nce  wit h  l ocal  pr oce d ures.  Ot her  c h a n ges  i n  s u bject 
healt h i nf or mati o n bec o mes A E dat a w he n t he s u bject be gi ns d osi n g wit h t he test article; 
t heref or e, A E data s h o ul d be c ollecte d fr o m t he date of t he first d ose of test article u ntil 
t he date of t he fi nal st u d y visit. T hese data are c o nsi dere d treat me nt-e mer ge nt A Es.  
T he  i n vesti gat or  will  i nstr uct  t he  s u bject  t o  re p ort  a n y  A Es  t hat  ma y  occ ur  d uri n g  t he 
st u d y.  At  eac h  visit,  t he  i n vesti gat or  sh o ul d  as k  t he  s u bject,  i n  n o n- directi ve  fas hi o n, 
a b o ut a n y c ha n ge i n t he s u bject’s o verall h ealt h stat us si nce t he pre vi o us visit. 
T he  se verit y  of  eac h  A E,  as  j u d ge d  b y t he  i n vesti gat or,  will  be  rec or de d  o n  t he 
a p pr o priate A E C R F a n d will be gra de d acc or di n g t o t he f oll o wi n g scale: 
Mil d - T he  A E  is  us uall y  tra nsie nt  a n d ma y  re q uire  o nl y  mi ni mal treat me nt  or 
t hera pe utic  i nter v e nti o n.  T he  e ve nt  d oes n ot  ge n erall y  i nterfere  wit h  us ual 
acti vities of dail y li vi n g.
M o der ate 
-  T he  A E  is  us uall y  alle viate d  wit h  a d diti o nal  s pecific  t hera pe utic 
i nter ve nti o n.  T he  e ve nt  i nterferes  wit h  usual  acti vities  of  dail y  li vi n g,  ca usi n g 
disc o mf ort,  b ut  p oses  n o  si g nifica nt  or  pe r ma n e nt  ris k  of  har m  t o  t he  researc h 
partici pa nt.
Se vere  - T he A E i nterr u pts us ual acti vities of dail y li vi n g or si g nifica ntl y affects 
cli nical stat us, or ma y re q uire i n te nsi ve t hera p e utic i nter ve nti o n.  
T he i n vesti gat or m ust deter mi ne t he relati o ns hi p of t he A E t o t h e test article acc or di n g t o 
t he f oll o wi n g cate g ori es: 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 7 of 5 9 
Rel ate d  - T here is a str o n g me dical e vi de n ce t o s u g gest t hat t he A E is relate d t o 
test article usa ge.
P ossi bl y  Rel ate d   -  T here  is  me dical  e vi de nce  t o  s u g gest  t hat  t he  A E  ma y  be 
relate d t o test articl e usa ge.
N ot Rel at e d  - T her e is n o me dical e vi de n ce t o s u g gest t hat t he A E ma y be relate d 
t o test article usa ge.
T he  i n vesti gat or  s h o ul d  cate g orize  t he  o ut c o me  of  t he  A E  acc or di n g  t o  t he  f oll o wi n g 
cate g ories:
  
F at al - Ter mi nati o n of life as a res ult of a n A E.
N ot  Rec o v ere d/ N ot  R es ol ve d -  A E  has  n ot  i m pr o ve d  or  t he  s u bject  has  n ot 
rec u perate d.
Rec o vere d/ Res ol ve d -  A E has i m pr o ve d or t he s u bject has rec u perate d.
Rec o vere d/ Res ol ve d  wit h  Se q uel ae 
- s u bject  rec u perate d  b ut  retai n e d  t he 
pat h ol o gical c o n diti o ns res ulti n g fr o m t he pri or disease or i nj ur y.
Rec o veri n g/ Res ol vi n g -  A E is i m pr o vi n g or t he s u bject is rec u p erati n g.
U n k n o w n  - N ot k n o w n, n ot o bser ve d, n ot rec or de d or s u bject ref use d. 
1 4. 3 
Seri o us A d verse E ve nt
A n  e ve nt  t hat  is  seri o us  m ust  be  rec o r de d  o n  t he  A E  C R F  a n d  o n  t he    S A E  Re p ort 
F or m, a n d r e q uires e x pe diti o us ha n dli n g t o  c o m pl y wit h re g ulat or y re q uire me nts. 
A n A E or s us pecte d a d verse reacti o n is c o nsi d ere d “seri o us” if, i n t he o pi ni o n of eit her 
t he i n vesti gat or or S p o ns or, it res ults i n a n y of t h e f oll o wi n g o utc o mes: 
Deat h; t he  e ve nt  m ust  b e  t he  ca use  of  deat h  f or  t he  S A E  t o  meet  t his  seri o us 
criteri o n.
Life-t hreate ni n g  A E; a n e ve nt i n w hic h t he s u bject was at ris k of deat h at t he ti me 
of t he e ve nt a n d n ot a n e ve nt t hat h y p ot he ticall y mi g ht ha ve ca us e d deat h if it ha d 
bee n m ore s e ver e.
Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n (f or 
≥2 4 h o urs).  
Persiste nt  or  si g nifica nt  i nca pacit y  or  s u bsta nti al  disr u pti o n  of  t he  a bilit y  t o 
c o n d uct n or mal life f u n cti o ns. 
C o n ge nital a n o mal y/ birt h defect. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 8 of 5 9 
I m p ort a nt me dical e ve nts; a me dical e ve nt(s) t hat ma y n ot res ult i n deat h, be life-
t hreate ni n g,  or  re q uir e  h os pitalizati o n  b ut,  base d  u p o n  ap pr o priat e  me dical 
j u d g me nt,  ma y  j e o par di ze  t he  s u bject  an d  ma y  re q uire  me dical  or  s ur gical 
i nter ve nti o n  t o  pre ve nt  o ne  of  t he  o utc o mes  liste d  i n  t he  defi niti o n  a b o ve. 
E x a m ples  of  s uc h  me dical  e ve nts i ncl u de  aller gi c br o nc h os p as m  re q uiri n g 
i nte nsi ve  treat me nt  i n  a n  e mer ge nc y  ro o m  or  at  h o me,  bl o o d  d yscrasias  or 
c o n v ulsi o ns t hat d o n ot res ult i n i n patie nt  h os pitalizati o n, or t he de vel o p me nt of 
dr u g d e pe n de nc y or dr u g a b use.  
E ve nts N O T c o nsi dere d t o be seri o us A Es are: 
H os pitalizati o ns  f or  t he  treat me nt,  w hi c h  w as  el ecti ve  or  pre- pla n n e d,  of  a  pre-
e xisti n g c o n diti o n t hat di d n ot w orse n, a n d 
Treat me nt o n a n e mer ge nc y, o ut patie nt basis, f or a n e ve nt n ot f ulfilli n g a n y of t he 
defi niti o ns of “seri o us” gi ve n a b o ve a n d n ot res ulti n g i n h os pital a d missi o n.
A Es classifie d as “s eri o us” b y eit her t he i n vesti gat or or t he S p o ns or re q uire e x pe diti o us 
ha n dli n g a n d re p orti n g t o   t o c o m pl y wit h re g ul at or y re q uire me nts. All S A Es, w het her 
rel ate d  or  u nrel ate d  t o  test  articl e,  m ust  be  i m me di atel y  re p orte d  b y  tele p h o ne  t o 
t he  Me dic al  M o nit or  a n d,  i n  t he  e ve nt  t h at  he/s he  is  u n a v ail a ble,  t o  t he  Pr oject 
M a n a ger  liste d  o n  t he  firs t  p a ge  of  t he  pr ot oc ol. Writte n  n otificati o n  of  all  S A Es 
s h o ul d  be  se nt  t o  t he  Pr oject  Ma na ger  b y e mail  or  c o nfir me d  fa csi mile  tra ns missi o n. 
T hese i ncl u de t h ose S A Es liste d i n t he pr ot oc ol or R L D Pac ka ge I ns ert a n d m ust i ncl u de 
a n assess me nt of w h et her t here is a reas o na bl e p ossi bilit y t hat t he dr u g ca us e d t he e ve nt. 
If  o nl y  li mite d  i nf or m ati o n  is  i nitiall y  a vailable,  f oll o w- u p  re p orts  are  re q uire d.  S h o ul d 
t he i n vesti gat or bec o m e a war e of a S A E (re gar dless of its relati o ns hi p t o test article) t hat 
occ urs  wit hi n  3 0  da ys  after  st o p pi n g  t he  test  article,  t he  S A E  m u st  be  re p orte d  i n 
acc or d a nce wit h pr oce d ures s pecifi e d i n t his pr ot oc ol. I n t he e v e nt of deat h, if a n a ut o ps y 
is perf or me d, a c o p y of t he re p ort sh o ul d be s e nt t o  
 if a vaila ble. 
U p o n recei vi n g s uc h n otices, t he i n vesti gat or m ust re vie w a n d retai n t he n otice wit h t he 
R L D  Pac ka ge  I nsert  a n d  pr o m ptl y  s u b mit  a  c o p y   of  t his  i nf or mati o n  t o  t he  res p o nsi ble 
I R B  acc or di n g  t o  l ocal  re g ul ati o ns.  T he  i n vesti gat or  a n d  I R B  will  deter mi ne  if  t he 
i nf or me d  c o nse nt  re q uir es  re visi o n.  T he  i n vesti gat or  s h o ul d  als o  c o m pl y  wit h  t he  I R B 
pr oce d ur es  f or  re p orti n g  a n y  ot her  s afet y i nf or mati o n.  W here  re q uire d,  s u b missi o n  of 
safet y  u p dates  b y  t he  i n vesti gat or  t o  Healt h  A ut h orities  s h o ul d  be  ha n dle d  acc or di n g  t o 
l ocal re g ulati o ns.
T he S p o ns or or desi g nee ma y be re q uire d t o re p ort certai n S A Es t o re g ulat or y a ut h orities 
(e. g., U nite d States  F D A) wit hi n se ve n cale n dar  da ys of bei n g n otifie d a b o ut t he e ve nt; 
t heref ore,  it  is  i m p orta nt  t hat  i n vesti gat ors  s u b mit  a n y  i nf or mati o n  re q ueste d  b y  t he 
S p o ns or or desi g n ee as s o o n as it bec o mes a v aila ble. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 3 9 of 5 9 
1 4. 4 
L a b or at or y Test A b n or m alities 
Alt h o u g h t her e are n o s p ecific la bs re q uire d i n t his st u d y, if a n a b n or mal la b orat or y res ult 
i n dicate d  as  cli nicall y  si g nifica nt  b y  t h e  i n vesti gat or  is  t he  reas o n  f or  a  s u bject  bei n g 
wit h dra w n fr o m t he st u d y or r e q uires treat me nt f or t he a b n or malit y, t his a b n or mal r es ult
m ust  als o  be  re p orte d  as  a n  A E.  I n  a d diti o n,  a n y  la b orat or y  test  res ult  t hat  meets  t he 
criteria  f or  a  S A E  (see Secti o n  1 4. 3 )  m ust  als o  be  re p orte d  as  a  S A E  s o    ca n  c ollect 
a d diti o nal  i nf or mati o n  a b o ut   t hat  a b n or malit y,  i ncl u di n g  i nf or m ati o n  re gar di n g 
relati o ns hi p t o test article or ot her ca uses, a n y acti o n ta ke n, a n d o utc o me. 
1 4. 5 
Pre g n a nc y
W O C B P i ncl u de a n y fe male w h o has e x perie nce d me narc he or is 1 0 years of a ge or ol der 
a n d w h o has n ot u n der g o ne s uccessf ul s ur gical sterilizati o n ( h ysterecto m y, bilateral t u bal 
li gati o n [at least si x m o nt hs pri or t o i nitiati o n of treat me nt], or bilateral o o p h orect o m y) or 
is  n ot  p ost me n o pa usal  ( defi ne d  as  a m e n orr hea  > 1 2  c o ns ec uti ve  m o nt hs  i n  w o me n  5 0 
years of  a ge a n d ol der).  E ve n w o me n w h o are usi n g o ne of t he  effecti ve  f or ms of birt h 
c o ntr ol per pr ot oc ol will be c o nsi dere d of c hil d beari n g p ot e ntial.  
W O C B P m ust ha ve a U P T pri or t o st u d y e nr oll me nt a n d m ust use a n effecti ve 1 9 met h o d 
of  birt h  c o ntr ol  d uri n g  t he  c o urse  of  t he  st u d y,   i n  a  m a n ner  s uc h  t h at  ris k  of  fail ure  is 
mi ni mize d.  Pri or  t o  st u d y  e nr oll me nt,  W O C B P  m ust  be  a d vise d  of  t he  i m p orta nce  of 
a v oi di n g  pr e g na n c y  d uri n g  t he  st u d y  a n d  t h e p ote ntial  ris k  fact ors  f or  a n  u ni nte nti o nal 
pre g na nc y. T he s u bject m ust si g n a n i nf or m e d c o nse nt f or m d oc u me nti n g t his disc ussi o n. 
W O C B P s h o ul d be i nstr ucte d t o c o ntact t he i n vesti gat or i m me diatel y if t h e y s us pect t he y 
mi g ht  be  pre g na nt  ( e. g.,  misse d  or  late  me nstr ual peri o d).  If  a  s u bject  or  i n vesti gat or 
s us pects t hat a s u bject m a y b e pre g na nt at a n y ti me d uri n g t he st u d y, t he test article m ust 
be wit h hel d u ntil t he res ults of la b orat or y pre g n a nc y t esti n g are a v aila ble. If pre g na n c y is 
c o nfir me d,  t he  s u bject  m ust  n ot  recei ve  or  a p pl y  f urt her  test  article  a n d  m ust  be 
disc o nti n ue d fr o m t he st u d y. 
If  f oll o wi n g  i nitiati o n  of  st u d y  treat me nt,  it  is  s u bse q ue ntl y  disc o vere d  t hat  a  st u d y 
s u bject was pre g na nt or ma y ha v e bee n pre g na nt at t he ti me of test article e x p os ure, t he 
i n vesti gat or m ust i m me diatel y  n otif y t he Me dical M o nit or of t his e ve nt, a n d rec or d t h e 
1 9 Effecti ve  f or ms  of  birt h  c o ntr ol  i ncl u de  a)  h or m o nal   c o ntrace pti ves  [ oral,  i nj ecta ble,  tra ns der mal  or 
i ntra va gi nal] f or o ne f ull c ycl e (e. g., f o ur t o ei g ht wee ks), or I U D f or o ne wee k, f or i nj ecta ble (e. g., De p o-
Pr o vera) t he re q uire me nt is at least se ve n da ys after i nj ecti o n, pri or t o test article a p plicati o n, or b) c o n d o m 
a n d s per mici dal, or dia p hra g m/cer vical ca p a n d s per mici dal w hic h are effecti ve as s o o n as t he birt h c o ntr ol 
met h o d is a d mi nistere d pr o perl y. Ot her acce pta ble f or ms of birt h c o ntr ol i ncl u de: a) a bsti ne nce f or s u bj ects 
w h o are n ot se x uall y acti ve or b) if t he s u bj ect is i n a m o n o ga m o us relati o ns hi p wit h a part ner w h o is sterile 
(e. g., a vasect o m y perf or me d at least si x m o nt hs pri or t o t he s u bj ect’s i nitiati o n of treat me nt). S u bj ects w h o 
bec o me  se x uall y acti ve or be gi n t o ha ve relati o ns  wit h a p art ner  w h o is  n ot sterile d uri n g t he st u d y  m ust 
a gree t o use a n effecti ve f or m of birt h c o ntr ol f or t he d urati o n of t he st u d y.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 0 of 5 9 
pre g na nc y o n t he a p pr o priate pre g n a nc y s ur v eilla nce f or m. T h e f or m will be se nt t o  
 
T he i n vesti gat or m ust n otif y t he I R B of a n y pre g na nc y ass o ciate d wit h t h e st u d y t h era p y 
a n d kee p car ef ul s o urce d oc u me ntati o n of t he e v e nt. 
Pr ot oc ol-re q uire d pr oce d ures f o r t h ose s u bjects t h at are disco nti n ue d fr o m t he st u d y m ust 
be  perf or me d  o n  t he  s u bject  u nl ess  c o ntrai n dicate d  b y  pre g na n c y  (e. g.,  x-ra y  st u dies). 
Ot her  a p pr o pri ate  pre g n a nc y  f oll o w- u p  pr oce d ures  s h o ul d  be  c o nsi dere d  if  i n dicate d, 
i ncl u di n g  c o u nseli n g  of  t he  s u bject  b y  t he  i n v esti gat or  a n d  h er  m a na gi n g  p h ysi cia n  or 
healt h car e pr o vi der (e. g., o bstetricia n). I n a d diti o n, t he i n vesti gat or m ust re p ort t o  , o n 
t he a p pr o priate   pr e g n a nc y s ur v eilla nce f or m(s), a n y  f oll o w- u p i nf or mati o n re gar di n g 
t he  c o urse  of  t he  pre g na nc y,  i ncl u di n g peri natal  a n d  ne o n atal  o utc o me.  Alt h o u g h 
pre g na nc y itself is n ot a n A E, a n y c o m plicati o ns d uri n g pre g n a nc y s h o ul d be rec or de d as 
A Es  or  S A Es  (if  t he y  f ulfill  t he S A E  criteria).  Offs pri n g  s h o ul d  b e  f oll o we d  f or  a 
mi ni m u m  of  ei g ht  wee ks.  A n y  c o n ge nital  a n o mal y/ birt h  defect  i n  a  c hil d  b or n  t o  a 
s u bject e x p ose d t o t he test article(s) s h o ul d be rec or de d as a S A E a n d details d oc u me nte d 
i n  t he  pre g na n c y  s ur v eilla nce  f or m.  A b orti o n,  w het her  acci d e ntal,  t hera pe utic,  or 
s p o nta ne o us s h o ul d be re p orte d as a S A E. 
1 5. 
B LI N DI N G/ U N B LI N DI N G
T his  is  a  d o u ble- bli n d,  r a n d o mize d,  place b o-c o nt r olle d  st u d y.  Bli n di n g  is  i m p orta nt  f or 
t he i nte grit y of t his cli nical dr u g st u d y. H o we v er, t he bli n d ma y b e br o ke n i n t he e ve nt of 
a  me dical  e mer ge nc y  i n  a  s u bject,  i n  w hic h k n o wle d ge  of  t he  test article  i de ntit y  is 
critical  t o  t he  s u bject’s  ma na ge m e nt.  Bef ore  brea ki n g  t he  bli n d  f or  a  s u bject,  t he 
i n vesti gat or s h o ul d deter mi ne t hat t he i nf or mati o n is necessar y (i.e., t hat it will alter t he 
s u bject’s i m me diate ma na ge me nt). If p ossi ble, t he nee d t o brea k t he bli n d s h o ul d first be 
disc usse d  wit h  t he  res p o nsi ble  Me dical  M o n it or  a n d  t he  best  met h o d  t o  d o  t his  will  be 
deter mi ne d.
1 6.  
C LI NI C A L S U P P LI E S
1 6. 1 
Test Articl e I nf or m ati o n
Detaile d  i nf or mati o n  o n  t he  pac ka gi n g/la b e li n g,  bli n di n g/ u n bli n di n g,  st ora ge  a n d 
pre par ati o n, dis pe nsi n g, acc o u nta bilit y, etc.  of t h e test article is i ncl u de d i n A p pe n di x 2 . 
1 6. 2 
S u p plies Pr o vi de d b y 
C R Fs
Site re g ulat or y bi n der
U P T kits
Tra ns par e ncies ( pre- mar ke d 1 c m 2 gri d) a n d mar k ers t o i de ntif y t h e treat me nt area
Treat me nt Area I de ntificati o n Ma n ual

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 1 of 5 9 
1 6. 3 
S u p plies Pr o vi de d b y I n vesti g at or 
Uri ne c ollecti o n c o nt ai ners 
1 6. 4 
S u p plies Pr o vi de d b y G a ge  De vel o p me nt C o m p a n y, L L C 
Sa m ples f or de m o nstrati o n t o s u bjects of test article a p plicati o n
Di gital ca mera, p h ot o pr i nter, a n d s u p plies. 
1 7. 
S T A TI S TI C A L C O N SI D E R A TI O N S
1 7. 1 
S a m ple Size
Base d o n 
pr o ba bilit y of de m o nstrati n g t hera p e utic e q ui vale n ce bet wee n t he acti ve treat me nts a n d at 
t he  sa me  ti me  s h o wi n g  t hat  eac h  acti ve  treat me nt  is  s u peri or  t o  t he  ve hicle  treat me nt. 
T h us,  a p pr o xi matel y  
s u bjects  will  be  e nr olle d  i nt o  t he  st u d y  t o  o btai n  
mI T T 
s u bjects.
1 7. 2 
E n d p oi nts
1 7. 2. 1 Effic ac y E n d p oi nts 
T he  pri mar y  efficac y  e n d p oi nt  is  t he  pr o p or ti o n  of  s u bjects  i n  t he  P P  p o p ulati o n  wit h 
treat me nt  s uccess  ( “ C o m plete  Cleara n ce”) at  D a y  9 0  ( 3 0  d a ys  after  c o m pleti o n  of  6 0 
da ys of treat me nt). C o m plete Cleara n ce is defi ne d as 1 0 0 % cleara nce of  all A K lesi o ns 
( ha vi n g a c o u nt of zer o A Ks) i n t he 2 5 c m2 treat me nt area (face or bal d s cal p) at t he Da y 
9 0  visit.  All  A Ks  (t h ose  prese nt  at  baseli ne a n d  ne w  lesi o ns,  if  a n y  t hat  ma y  de v el o p) 
i n de pe n de nt of size wit hi n t he 2 5 c m2 treat me nt area are t o be treate d a n d i ncl u de d i n t he 
efficac y lesi o n c o u nt f or eac h visit. 
1 7. 2. 2 S af et y E n d p oi nts
D osi n g C o m plia nce 
Meas ures of test article c o m plia nce will i ncl u de t he t otal n u m ber of a p plicati o ns rec or de d 
i n  t he  C R Fs  a n d  verifi e d  fr o m  t he  data  i n  t he  s u bject  diaries.  C o m plia nt  s u bjects  are 
defi ne d as t h ose w h o a p pl y at least 7 5 % a n d n o m ore t ha n 1 2 5 % of t he e x pecte d ( 1 2 0) 
test  article  a p plicati o ns,  di d  n ot  miss  m ore  t ha n  1 0  c o nsec uti ve  sc h e d ule d  a p plicati o ns, 
a n d ha ve n o ot her e vi de n ce of material d osi n g n o n c o m plia nce.
A d verse E v e nts a n d L ocal S ki n Reacti o ns
Se verit y  a n d  fr e q ue nc y  of  A Es  i ncl u di n g  L S Rs  (er yt he ma,  dr y n ess/fla ki n g/scali n g, 
b ur ni n g/sti n gi n g,  er osi o n/ ulcerati o n,  e de ma,  pa i n,  a n d  pr urit us)  will be  assesse d  i n  t he 
t hree treat me nt gr o u ps. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 2 of 5 9 
1 7. 3 
St atistic al Met h o ds
All statistical pr ocessi n g will be perf or me d usi n g S A S ® u nless ot her wise state d. 
T he  Safet y  p o p ulati o n  will  i ncl u de  all  ra n d o mi ze d  s u bjects  w h o  recei ve d  t he  test  article. 
T he mI T T p o p ulati o n will i ncl u de all ra n d o mize d  s u bjects w h o met all i ncl usi o n/e xcl usi o n 
criteria, a p plie d at least o ne d ose of test artic le, a n d ret ur ne d f or at least o ne p ost- baseli ne 
e val uati o n visit. Ra n d o mize d s u bjects w h o are l ost t o f oll o w- u p after Visit 1, w h o ret ur n 
f or t he E O T visit b ut ha ve n ot a p plie d a n y t est article, or w h o are f o u n d n ot t o ha ve met 
t he  eli gi bilit y  criteria  will  be  e x cl u de d  fro m  t h e  mI T T  p o p ulati o n. S u bjects  will  be 
i ncl u de d  i n  t he  P P  efficac y  a nal yses  if  t he y  met  all  t he  i ncl usi o n/e xcl usi o n  criteria,  were 
c o m plia nt wit h t he assi g ne d test articles (a p plie d at least 7 5 % a n d n o m ore t ha n 1 2 5 % of 
t he e x pecte d ( 1 2 0) t est article a p plicati o ns) f or t he s pecifie d d urati o n of t he st u d y, di d n ot 
miss m ore t ha n 1 0 c o nsec uti ve sc he d ul e d a p plicati o ns, ha ve n o ot her e vi de nce of material 
d osi n g  n o nc o m plia nce,  a n d  c o m plete d  t he  pri mar y  e n d p oi nt  e val uati o n at  t he  E O S  visit 
wit hi n t he desi g nate d visit wi n d o w ( ± 4 da ys) wit h n o pr ot oc ol vi olati o ns t hat w o ul d affect 
t he  treat me nt  e val uati o n.  S u bjects  w h o  are  disco nti n ue d  fr o m  t he  st u d y  d ue  t o  w orse ni n g 
c o n diti o n t hat re q uires alter nate or s u p ple me ntal t hera p y f or t he treat me nt of A K s h o ul d be 
i ncl u de d i n t he P P p o p ulati o n as treat me nt fail ures if t he y meet t he mI T T criteria. S u bjects 
w h o are disc o nti n ue d earl y fr o m t he st u d y d ue t o lac k of treat me nt effect after c o m pleti n g 
at  least  f o ur  wee ks  of  treat me nt  s h o ul d  be  i ncl u de d  i n  t he  mI T T  a n d  P P  p o p ulati o n  as 
treat me nt  fail ures.  S u bjects  disc o nti n ue d  early  f or  ot her  reas o ns  s h o ul d  be  e xcl u de d  fr o m 
t he  P P  p o p ulati o n,  b ut  i ncl u de d  i n  t he  mI T T  p o p ulati o n,  usi n g  last- o bser vati o n-carrie d-
f or war d ( L O C F).
Efficac y s u m maries a n d a nal yses will be carrie d o ut i n t he mI T T a n d P P p o p ulati o ns. All 
s u m maries  of  safet y  will  be  carrie d  o ut  i n  t he  Safet y  p o p ulati o n.  L O C F  will  be  use d  t o 
i m p ute missi n g val ues f or efficac y varia bles i n t he mI T T p o p ulati o n. 
De m o gra p hic a n d baseli ne c h ar acteristics will b e s u m marize d b y treat me nt gr o u p f or all 
a nal ysis  p o p ulati o ns.  T he  size  of  t he  treat me nt  area  i n  c m 2 will  be  s u m marize d  b y 
treat me nt gr o u p f or t he mI T T a n d P P p o p ulatio ns. Fre q u e nc y c o u nts a n d perce nt a ges will 
be  re p orte d  f or  cate g orical  data.  Sa m ple size,  mea n,  sta n dar d de viati o n,  mi ni m u m,  a n d 
ma xi m u m will be re p orte d f or t he c o nti n u o us vari a bles. 
1 7. 3. 1 Effic ac y A n al yses 
T he  9 0 %  Wal d’s  c o nfi de nce  i nter v al  wit h  Yate’s  c o nti n uit y  c orrecti o n  will  be 
c o nstr ucte d  o n  t he  diff ere nce  bet w ee n  t h e  pr o p orti o ns  of  s u bjects  wit h  A K  lesi o n 
clear a nce i n t he T est a n d Refere n ce treat me nts t o e val uate t he t hera p e utic c o m para bilit y 
of t he t w o acti ve tr eat me nts. E val uati o n i n t he P P p o p ulati o n will be c o nsi dere d pri mar y. 
At  Da y  9 0  ( 3 0  da ys  after  c o m pleti o n  of  6 0  da ys  of  treat me nt),  if  t he  9 0 %  c o nfi de nce 
i nter val  o n  t he  differe nce  bet wee n  t he  Test  a n d  Refere n ce  lesi o n  cleara n ce  pr o p orti o ns 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 3 of 5 9 
are  c o ntai n e d  wit hi n  t he  i nter val  - 0. 2 0  t o + 0. 2 0,  t he n  t he  Test  a n d  Refere nce  pr o d u cts 
will be c o nsi dere d t o be t hera pe uticall y e q ui vale nt.
T w o-si de d, c o nti n uit y-c orrect e d C hi-s q uare t ests will be use d t o e val uate t he s u peri orit y 
of  eac h  acti ve  treat me nt’s  c o m plete  cleara nce  pr o p orti o n  o ver  t hat  of  t he  Ve hicle 
treat me nt i n t he mI T T p o p ulati o n usi n g L O C F. 
T he  t hera p e utic  c o m par a bilit y  e val uati o ns i n  t he  P P  p o p ulati o n  will  be  c o nsi dere d 
pri mar y,  w hile  t h ose  i n  t he  mI T T  p o p ula ti o n  will  be  c o nsi dere d  s u p p orti ve.  T he 
s u peri orit y c o m paris o ns i n t he mI T T p o p ul atio n will be c o nsi dere d pri mar y w hile t h ose 
i n t he P P p o p ulati o n will be c o nsi dere d s u p p orti ve. 
1 7. 3. 2 S af et y A n al yses 
All s u bjects i n t he Safet y p o p ulati o n will be i ncl u de d i n s u m maries of safet y data. 
1 7. 3. 2. 1  
D osi n g C o m plia nce 
Descri pti ve statistics will be use d t o s u m marize test article c o m plia nce f or t he mI T T a n d 
P P  p o p ulati o ns.  Meas ures  of  te st  article  c o m plia nce  will  i ncl u de  t he  t otal  n u m ber  of 
a p plicati o ns  as  d eter mi n e d  fr o m  t he  dat a  rec or de d  i n  t he  s u bj ect  diaries.  C o m plia nt 
s u bjects are defi ne d as t h ose w h o a p pl y at least 7 5 % a n d n o m ore t ha n 1 2 5 % of e x pecte d 
( 1 2 0)  test  article  a p pli cati o ns,  di d  n ot  miss  m ore  t ha n  1 0  c o ns ec uti ve  sc he d ul e d 
a p plicati o ns, a n d ha ve n o ot her e vi de n ce of mat eri al d osi n g n o nc o m plia nce. 
1 7. 3. 2. 2  
A d verse E v e nts
All A Es will be c o de d usi n g t he Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A) 
c o di n g dicti o nar y. T h e n u m ber a n d perce nt of u ni q ue s u bjects re p orti n g eac h treat me nt-
e mer ge nt  A E  will  be  s u m marize d  b y  M e d D R A  s yste m  or ga n  class  ( S O C),  Me d D R A 
preferre d  ter m  ( P T),  a n d  treat me nt  gr o u p. A Es  will  als o  be  si milarl y  s u m marize d  b y 
S O C,  P T,  ma xi m u m  se verit y, a n d  treat me nt  gr o u p  as  well  as  b y  S O C,  P T,  cl osest 
relati o ns hi p t o test article, a n d treat me nt gr o u p. All A Es re p orte d d ur i n g t he st u d y will be 
liste d, d oc u me nti n g c o urse, se verit y, i n vesti gat or assess me nt of t he relati o ns hi p t o t he test 
articles, a n d o utc o m e.  
1 7. 3. 2. 3 
L ocal S ki n Reacti o ns 
T he  fr e q ue n c y  of  t he  i n di vi d ual  
L S Rs 
(er yt h e ma,  dr y n ess/fla ki n g/scali n g, 
b ur ni n g/sti n gi n g,  er osi o n/ ulcerati o n,  e d e ma, pai n,  a n d  pr urit us)  w ill  be  ta b ulate d  b y 
se verit y a n d treat me nt gr o u p at eac h o nsite cli nic visit.
1 7. 4 
S u b gr o u p A n al yses
N o s u b gr o u p a nal ysis is pla n ne d.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 4 of 5 9 
1 7. 5 
I nteri m A n al yses
N o i nteri m a nal ysis is pla n ne d.
1 8. 
E T HI C A L A N D R E G U L A T O R Y C O N SI D E R A TI O N S
1 8. 1  
C o m pli a nce wit h G o o d  Cli nic al Pr actice
T his  st u d y  will  be  c o n d ucte d  i n  c o m plia nce  wit h  t he  pri nci ples  of  t he  Declarati o n  of 
Helsi n ki,  wit h  t he  c urre nt  G o o d  Cli nical  Practice  g ui deli nes  a n d  wit h  ot her  a p plica ble 
re g ulati o ns. T he i n vesti gat or a n d all st u d y staff will c o n d uct t he st u d y i n c o m plia nce wit h 
t his  pr ot oc ol.  T he  pr ot oc ol,  i nf or me d  c o nse nt  d oc u me nts,  recr uit me nt  a d vertise me nts, 
a n d  a n y a me n d me nts  t o  t hese  ite ms  will  ha ve  I R B  a p pr o val  pri or  t o  st u d y  i nitiati o n. 
V ol u ntar y i nf or me d c o ns e nt will be gi ve n b y e ver y s u bject pri or t o t he i nitiati o n of a n y 
st u d y-r elate d pr o ce d ur es. T he ri g hts, safet y, a n d well- bei n g of t he st u d y s u bjects are t he
m ost  i m p orta nt  c o nsi derati o ns a n d  pre vail  o ver  t he  i nterests of  scie nce  a n d  s ociet y.  All 
pers o n nel i n v ol ve d i n t h e c o n d uct of t his st u d y m ust be q ualifie d b y e d u cati o n, trai ni n g, 
a n d e x perie nce t o perf or m t heir assi g ne d res p o nsi bilities. C orrect c o ntact i nf or mati o n f or 
eac h site a n d a n y ve n d ors use d i n t he st u d y w ill b e ke pt i n a se parate refere nce d o c u me nt.
1 8. 2 
I nstit uti o n al Re vie w B o ar d a n d I nf or me d C o nse nt
Bef ore  st u d y  i nitiati o n,  t he  i n vesti gat or  m u st  h a v e  writte n  a n d  d ate d  a p pr o val  fr o m  t h e 
I R B  f or  t he  pr ot oc ol,  c o nse nt  f or m,  s u bject  recr uit me nt  materi als/ pr ocess  (e. g., 
a d vertise me nts),  a n d  a n y  ot her  writte n  i nf or mati o n  t o  be  pr o vi de d  t o  s u bjects.  T he 
i n vesti gat or s h o ul d als o pr o vi de t he I R B wit h a c o p y of t he pr o d uct la beli n g, i nf or mati o n 
t o be pr o vi de d t o s u bjects (if a p plica ble), a n d a n y u p d ates. T h e i n vesti gat or will s u b mit 
d oc u me ntati o n of t he I R B a p pr o v al t o  .  
T he  I R B- a p pr o ve d  c o ns e nt  f or m  m ust  i ncl u de all  ele me nts  re q uire d  b y  F D A,  state,  a n d 
l ocal re g ulati o ns, a n d ma y i ncl u de a p pr o pri ate a d diti o nal ele me nts.
T he i n vesti gat or/ desi g nee will e x plai n t he st u d y t o eac h p ote ntial s u bject a n d t he s u bject 
m ust  i n dicate  v ol u ntar y  c o nse nt  b y  si g ni n g a n d  dati n g  t h e  a p pr o ve d  i nf or me d  c o ns e nt 
f or m.  T he  i n v esti gat or  m ust  pr o vi de  t he  s u bject  wit h  a  c o p y  of  t he  c o nse nt  f or m  i n  a 
la n g u a ge t he s u bject u n dersta n ds.  
T he i n vesti gat or will mai ntai n d oc u me ntati o n t hat i nf or me d c o ns e nt was o btai ne d pri or t o 
t he i nitiati o n of a n y st u d y-s p ecific pr oce d ures.
1 8. 3 
Pr ot oc ol C o m pli a nce 
T he  I R B-a p pr o ve d  pr ot oc ol  m ust  be  f oll o w e d  e x ce pt  i n  t he  case  of  a  c ha n ge  t hat  is 
i nte n de d  t o  eli mi nate  a n  i m me diate  ris k  t o  s u bjects.  All  pr ot oc ol  de vi ati o ns  m ust  be 
d oc u me nte d. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 5 of 5 9 
1 8. 4 
Pr ot oc ol R e visi o ns 
  m ust  pre p are  all  pr ot oc ol  re visi o ns.  All  pr ot oc ol  a me n d me nts  m ust  recei ve  I R B 
a p pr o val pri or t o i m ple me ntati o n. All a d mi nistrati ve letters m ust be s u b mitte d t o t he I R B 
f or  t heir  i nf or mati o n.  C o pies  of  all  c orresp o n de nce  wit h  t he  I R B  re gar di n g  t his  st u d y 
m ust be se nt t o  
 
Ne w  or  altere d  c o ns e nt  f or ms re q uire d  b y  t he  I R B  d ue  t o a  pr ot oc ol  c ha n ge  m ust  be
si g ne d b y all s u bjects c urre ntl y e nr olle d i n t he st u d y a n d m ust be us e d f or a n y s u bs e q ue nt 
s u bject e nr oll me nt.
1 8. 5 
St u d y M o nit ori n g
Re prese ntati ves  of  
  a n d/ or  t he  S p o ns or  m ust   be  all o we d  t o  visit all  st u d y  sites,  t o 
re vie w st u d y rec or ds a n d t o directl y c o m pare t he m wit h s o urce d oc u me nts (i ncl u di n g, b ut 
n ot  li mite d  t o  patie nt  a n d  h os pital  rec or ds),  t o  disc uss  t he  st u d y  c o n d uct  wit h  t he 
i n vesti gat or a n d st u d y staff, a n d t o verif y t hat t h e i n vesti gat or, st u d y staff, a n d facilities 
re mai n acce pta bl e f or t he c o n d uct of t he st u d y. 
Re prese ntati ves  of  g o v er n me nt  re g ul at or y  a ut h orities  ma y  als o  e val uate  t he  st u d y 
rec or ds, s o urce d o c u me nts, i n vesti gat or, st u d y staff, a n d facilities. 
T he  i n vesti gat or  s h o ul d  i m me diatel y  n otif y  
 of  a n y  a u dits  of  t his  st u d y  b y  a n y 
re g ulat or y a ge nc y, a n d m ust pr o m ptl y pr o vi de c o pies of a n y a u dit re p orts. 
1 8. 6  
C ase Re p ort F or m R e q uire me nts
T he st u d y will utilize vali date d 2 1 C F R Part 1 1 c o m plia nt E D C s oft ware t o c ollect data. 
All re q ueste d i nf or mati o n m ust be e ntere d o n t h e electr o nic C R Fs (e C R Fs) i n t he areas 
pr o vi de d  i n  a  ti mel y  ma n ner.  W he n  c h a n ges  or  c orrecti o ns  are  ma de  i n  t he  e C R F,  t he 
E D C s yste m will mai ntai n a c o m plete a u dit tr ail of t he p ers o n ma ki n g t he c h a n ges, t he 
date  a n d  ti me  of  t he  c ha n ge  a n d  t he  reas o n  f or  t he  c ha n ge.  O nl y  i n di vi d uals  w h o  ha ve 
c o m plete d  E D C  trai ni n g  a n d are  liste d  o n  t he  D ele gati o n of  Res p o nsi bilities  L o g  wit h 
res p o nsi bilit y f or e C R F c o m pletio n will be pr o vi de d user na m es a n d pass w or ds i n or der t o 
access t he s yst e m a n d ma ke e ntries o n t he e C R Fs. 
T he  i n vesti gat or or  p h ysicia n  s u b-i n vesti gat or   m ust  electr o nicall y  si g n  a n d  date  eac h 
s u bject’s e C R F. I n di vi d u als w h o will be pr o vi di n g el ectr o nic si g nat ures m ust first s u b mit 
d oc u me ntati o n wit h a ha n d writte n si g nat ure ac k n o wle d gi n g t hat t heir electr o nic si g n at ure 
is a le gall y bi n di n g e q ui v ale nt t o t heir ha n d writte n si g nat ure. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 6 of 5 9 
1 8. 7  
Re p orts t o I nstit ut i o n al Re vie w B o ar d 
T he  i n vesti gat or  s h o ul d  pr o vi de  t he  I R B  w it h  re p orts,  u p dates,  a n d  ot h er  i nf or mati o n 
(e. g.,  safet y  u p d ates,  pr ot oc ol  a me n d me nts,  a n d  a d mi nistrati ve  letters)  acc or di n g  t o 
re g ulat or y re q uire me nts or I nstit uti o n pr oce d ures. 
1 8. 8  
Q u alit y Ass ur a nce A u dits
Re prese ntati ves fr o m  
a n d/ or t he S p o ns or or a t hir d part y selecte d b y t h e S p o ns or ma y 
c o n d uct  a  q u alit y  ass ura nce  a u dit  of  t his  st u d y.  D uri n g  t he  a u dit,  t he  i n vesti gat or  m ust 
pr o vi de t he a u dit or wit h direct access t o a ll rel e v a nt d oc u me nts a n d disc uss a n y fi n di n gs 
wit h t he a u dit or. 
I n t he e ve nt of a n i ns pecti o n b y t h e F D A or ot her re g ulat or y a ut h orities, t he i n vesti gat or 
m ust gi ve t he i ns pect or  direct access t o rele v a nt  d oc u me nts a n d t o disc uss a n y fi n di n gs 
wit h t he i ns pect or. T he i n vesti gat or m ust n otif y  
i n t he e ve nt of a F D A site a u dit. 
1 8. 9  
Rec or ds R ete nti o n
Acc or di n g t o 2 1 C F R § 3 1 2. 6 2, a n i n vesti gat or is re q uire d t o m ai ntai n st u d y rec or ds f or a 
peri o d of t w o  years f oll o wi n g t h e dat e a mar k eti n g a p plicati o n is a p pr o ve d f or t h e dr u g 
f or t he i n dicati o n f or w hi c h it is bei n g i n vesti gate d; or, if n o a p plicati o n is t o be file d or if 
t he a p plicati o n is n ot a p pr o ve d f or s uc h i n dicati o n, u ntil t w o years after t he i n vesti gati o n
is disc o nti n ue d a n d t he F D A is n otifie d. 
Eac h site will be re q uire d t o ra n d o ml y select res er ve sa m ples fr o m t he s hi p me nt of test 
articles. I nstr u cti o ns o n t he n u m ber of kits t o  select a n d h o w t o d o c u me nt t he kit n u m bers 
selecte d as res er ve sa m pl es will be i ncl u de d i n t he s hi p me nt. Eac h site will t he n st ore t he 
reser v e sa m ples. I n acc or da nce wit h 2 1 C F R § 3 2 0. 3 8, eac h reser v e sa m pl e (retai n) s h all 
be  st ore d  u n der  c o n diti o ns  c o ns iste nt  wit h  pr o d uct  la beli n g  a n d  i n  a n  area  se gre gate d 
fr o m t he area w here testi n g is c o n d ucte d a n d wit h access li mite d t o a ut h ori ze d pers o n nel. 
Eac h reser ve sa m ple s h all be retai ne d f or a peri o d of at l east fi ve years f oll o wi n g t he d ate 
o n w hic h t he a p plicati o n or s u p ple me ntal a p plicati o n is a p pr o ve d, or, if s uc h a p plicati o n 
or  s u p ple me ntal  a p plicati o n  is  n ot  a p pr o v e d, at  least  fi ve  years  f oll o wi n g  t h e  dat e  of 
c o m pleti o n of t he bi oa vaila bilit y st u d y fr o m w hi c h t he reser v e sa m ples w ere o btai ne d. 
T he  i n vesti gat or  m ust  c o ntact  
  or  t h e  S p o ns or  i n  writi n g  t o  o btai n  c o nse nt  pri or  t o 
destr o yi n g a n y rec or ds or reser v e sa m ples ass o ciate d wit h t his st u d y.
If t he i n v esti gat or wit h dra ws fr o m t h e st u d y, t he rec or ds s h all be tra nsferre d t o a m ut uall y 
a gree d u p o n d esi g nee. Writte n n otificati o n of s uc h a tra nsfer m ust be gi ve n t o  
 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 7 of 5 9 
1 8. 1 0  Rec or d C o nfi de nti alit y
All la b orat or y s peci me ns, e val uati o n f or ms, re p orts, a n d ot her rec or ds will be i de ntifie d 
i n  a  ma n ner  d esi g n e d  t o  mai ntai n  s u bject  c o nfi d e ntialit y.  All  rec or ds  will  be  ke pt  i n  a 
sec ure st or a ge area wit h li mite d access. Cli nical i nf or mati o n will n ot be release d wit h o ut 
t he  writte n  per missi o n  of  t he  s u bject,  e x ce pt  as  necessar y  f or  m o nit ori n g  b y  
or  t h e 
S p o ns or, t he F D A or ot h er re g ul at or y a ut h orit y, or t he I R B. 
T he  i n vesti gat or  a n d  all  e m pl o yees  a n d  c o w o r k ers  i n v ol ve d  wit h  t his  st u d y  s h all  n ot 
discl ose or use f or a n y p ur p ose ot her t ha n pe rf or ma nce of t he st u d y, a n y data, rec or ds, or 
ot her u n p u blis he d, c o nfi de ntial i n f or mati o n discl ose d t o t h ose i n di vi d uals f or t he p ur p ose 
of  t he  st u d y.  Pri or  writte n  a gree me nt  fr o m    or  t he  S p o ns or  m ust  be  o btai ne d  f or  t he 
discl os ure of a n y s ai d c o nfi de ntial i nf or mati o n t o ot her parties. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 8 of 5 9 
1 9.  
R E F E R E N C E S
1. Calle n J P, Bic kers D R, M o y R L. Acti nic kerat os es. J A m Ac a d Der m at ol . 1 9 9 7; 3 6: 
6 5 0- 6 5 3. 
2.  
Wari n o  L,  T usa  M,  Ca mac h o  F,  Te us c h ler  H,  Fleisc her,  A B  Jr,  Fel d ma n,  S R. 
Fre q u e nc y  a n d  c ost  of  ac ti nic  kerat osis  treat me nt. Der m at ol  S ur g .  2 0 0 6;  3 2:  1 0 4 5-
1 0 4 9.
3.  Mer k  H F.  T o pical  dicl ofe nac  i n  t he  treat me nt  of  acti nic  k erat oses. I nt  J  Der m at ol.
2 0 0 7; 4 6: 1 2- 1 8. 
4.  Dicl ofe nac s o di u m gel, 3 % [ pac ka g e i nsert]. Mel ville, N Y: F o u gera; 2 0 1 6. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 4 9 of 5 9 
A P P E N DI X 1 
S A M P L E S U B J E C T I N S T R U C TI O N S H E E T
C o pies  of  t he  f oll o wi n g  s u bject  i nstr ucti o ns  will  be  pr o vi de d  t o  t he  st u d y  site.  T he 
i n vesti gat or m ust gi ve eac h s u bject a c o p y of t his i nstr ucti o n s heet at t he Baseli ne Visit.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 0 of 5 9 
S a m ple S u bject I nstr ucti o n S heet
T he st u d y staff has i de ntifie d t he treat me nt area w here y o u s h o ul d a p pl y st u d y me dicati o n: 
Face (e xcl u di n g ears) or   
Bal d scal p  
A p pl y t he st u d y me dicati o n t wice a da y, o nce i n t he m or ni n g a n d o nce i n t he e ve ni n g, f or 6 0 
c o nsec uti ve  da ys  t o  t he  e ntire  2 5  c m 2 treat me nt  area.  Use  t he  p h ot o gra p h  a n d  te m plate 
pr o vi de d t o y o u b y t he st u d y staff at y o ur first vi sit t o hel p y o u i de ntif y t he area t o a p pl y t he 
st u d y me dicati o n. 
M ost  s u bjects  will  e x perie nce  l ocal  s ki n  re acti o ns  i n  a n d  ar o u n d  t he  treat me nt  area.  L ocal 
s ki n reacti o ns ma y i ncl u de: s ki n re d ness, sca b bi n g or cr usti n g, fla ki n g, scali n g, pai n, itc hi n g, 
or  dr y ness,  a n d  i n  s o me  cases  s welli n g,  s ore s  or  blisters,  a n d/ or  drai ni n g ( wee pi n g)  ma y 
de vel o p. T he s ki n res p o nses ca n var y fr o m mil d t o se vere. Y o u ma y als o see a n i ncrease i n 
t he  n u m ber  of  A K  gr o wt hs  as  pre vi o usl y  hid de n  A K  gr o wt hs  ma y  bec o me  visi ble  wit h 
treat me nt.
N O T E:  It  is  i m p ort a nt  f or  y o u  t o  c o nti n ue t o  use  t he  st u d y  me dic ati o n  t wice  d ail y 
d uri n g  t he  prescri be d  6 0- d a y  tre at me nt  peri o d  u nless  directe d  t o  d o  ot her wise  b y  t he 
st u d y  d oct or.  D o  n ot  disc o nti n ue  t he  use  of  t he  me dic ati o n  u nless  directe d  s o  b y  t he 
st u d y st aff. Tal k t o t he st u d y staff a b o ut a n y si de effects t hat y o u e x perie nce.  
Please  f oll o w  t hese  i nstr ucti o ns  caref ull y. C o ntact  t he  st u d y  staff  at  t he  tele p h o ne  n u m ber 
bel o w if y o u ha ve a n y q ue sti o ns a b o ut t he st u d y. 
Na me: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  P h o ne: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
T he site staff will i nstr uct y o u t o a p pl y t he gel t wice dail y, o nce i n t he m or ni n g a n d o nce 
i n  t he  e ve ni n g,  f or  6 0  c o nsec uti ve  da ys  usi n g  t he  p h ot o gra p h  a n d  te m plate  pr o vi de d  t o 
y o u t o hel p y o u i de ntif y t h e c orrect area t o treat at eac h a p plicati o n.  
D o  n ot  a p pl y  a n y  m oist urizers,  s u n  scree n,  ma ke- u p,  crea ms,  l oti o ns,  p o w ders,  or  a n y 
t o pical pr o d uct ot her t ha n t he st u d y me dicati o n gel t o t he treat me nt area. 
D o n ot c o ver t he treat me nt area wit h  ba n da ges or ot her cl ose d dressi n gs. 
D o  n ot  use  s u nla m ps,  ultra vi ole t  li g hts  or  ta n ni n g  be ds,  a n d a v oi d  s u nli g ht  as  m uc h  as 
p ossi ble  d uri n g  treat me nt  wit h  t he  st u d y  me di cati o n.  Use  pr otecti ve  cl ot hi n g  if  y o u  g o 
o utsi de d uri n g da yli g ht. 
If y o u miss a d ose, a p pl y t he ne xt d ose at t he re g ular ti me.  
Rec or d a n y misse d d oses i n y o ur st u d y diar y. 
If y o u get t he st u d y me dicati o n i n y o ur m o ut h or e yes, ri nse well wit h water ri g ht a wa y. 
D o n ot all o w a n y o ne else t o use t his st u d y me dicati o n. 
Kee p st u d y me dicati o n o ut of reac h fr o m c hil dre n. 
D o n ot use a n y ot her t o pical pr o d ucts (e. g., p o w ders, oi nt me nt, crea ms, l oti o ns, s ol uti o ns, 
s u n scree n, etc.) o n t he treat me nt area wit h o ut a p pr o val fr o m y o ur st u d y d oct or. 
D o n ot a p pl y t he st u d y me dicati o n t o t he treat me nt area pri or t o a n y st u d y visits. 
St ore t he st u d y me dicati o n at r o o m te m perat ure. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 1 of 5 9 
S u bject I nstr ucti o ns f or A p plic ati o n of Gels
Bef ore E ac h Use:  Was h y o ur ha n ds. Re m o ve t he ca p fr o m t he t u be. 
A p plic ati o n:
1.  Use t he st u d y me dicati o n t wice a da y as i n str ucte d b y y o ur st u dy d oct or. Use it o nl y o n 
y o ur s ki n.  
2.  Use t he p h ot o gra p h a n d te m plate gi ve n t o y o u b y  st u d y staff at y o ur first visit t o i de ntif y 
t he c orrect area t o a p pl y t he st u d y me dicati o n.  
3.  Dis pe nse  t he  re q uire d  a m o u nt  of  st u d y  me di cati o n  i nt o  t he  pal m  of  y o ur  ha n d.  U p  t o 
0. 5 gra m (e. g., sli g htl y s maller t ha n t he size of a di me) of st u d y me dicati o n s h o ul d be 
use d t o treat t he e ntire treat me nt area at eac h a p plicati o n. 
Usi n g  t he  ot her  ha n d,  a p pl y  s mall  ali q u ots  (“ d ot s”)  of  st u d y  me dicati o n  o ver  t he  e ntire 
2 5 c m 2 treat me nt area.
4.  Usi n g y o ur fi n gers, ge ntl y r u b t he st u d y me dicati o n i nt o y o ur s ki n s o t hat a u nif or m t hi n 
c oat c o vers t he e ntire 2 5 c m 2 treat me nt area (face or bal d scal p).  
5. Care s h o ul d be ta ke n n ot t o a p pl y st u d y me dicati o n near t h e e yes, n ostrils, a n d m o ut h. 
6. Be a bs ol utel y s ure t hat lesi o ns i de ntifie d at t he Baseli ne Visit are a de q uatel y c o vere d.
7.  
Was h y o ur ha n ds as s o o n as y o u fi nis h p utti n g t he st u d y me dicati o n o n y o ur s ki n. 
8.  A v oi d  tra nsferri n g  t he  st u d y  me dicati o n t o  ot her  h o use h ol d  me m bers  usi n g  c o m m o n 
t o wels, s ki n t o s ki n c o ntact after a p plicati o n, etc.
F or E ac h A p plic ati o n: R u b t he st u d y me dicati o n i nt o y o ur s ki n u ntil y o u ca n n o l o n ger see 
t he gel. D o n ot get t he st u d y me dicati o n i n or near y o ur e yes, i n or o n y o ur n ostrils, li ps or, 
f or w o me n, i n t he va gi na. Was h y o ur ha n ds wit h mil d s oa p a n d water. Rec or d t he a p plicati o n 
of st u d y me dicati o n i n y o ur st u d y diar y. D o n ot ta ke a bat h, was h, or get t he treat me nt area 
wet f or at least 4 h o urs after a p plicati o n.  

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 2 of 5 9 
St u d y Visit Sc he d ule:
Visit
Cale n dar Da y
Date
Ti me
2 ( P h o ne Call)
3
4 ( P h o ne Call)
5
6
Bri n g t his i nstr ucti o n s heet, use d a n d u n use d st u d y me dic ati o ns a n d y o ur di ar y t o e ac h 
st u d y visit.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 3 of 5 9 
A P P E N DI X 2 
T E S T A R TI C L E I N F O R M A TI O N
A 2. 1 Test Articl e P ac k a gi n g a n d L a beli n g
G D C  6 9 5  a n d  ve hicle  gel  f or m ula ti o ns  will  be  ma n ufact ure d  b y 
a n d  Di cl ofe nac  S o di u m  Gel,  3 %  will  be  p urc hase d  b y  
  T he  test 
articles  will  be  bli n de d  b y  p ac k a gi n g  G D C  6 9 5  a n d  ve hicl e  gel  i n  t u bes  t hat  are 
i n disti n g uis ha ble  fr o m  t he  Dicl ofe n ac  S o di u m  Gel,  3 %  t u be.  All  test  article  t u bes  will 
ha ve i de ntical l a bels as d escri be d b el o w. 
 will la bel t he 
test articles. 
Sites will be pr o vi de d  wit h sa m ples f or d e m o nstrati o n use o nl y t o trai n s u bjects o n t he 
a p plicati o n of t he test arti cle. 
T u be La bel
T u bes will be la bele d wit h a t w o- part la b el t hat will ha ve a scratc h- off pa n el t hat c o ntai ns 
t he  i de ntit y  of  t he  st u d y  me dicati o n.  I n  t he  e v e nt  of  e mer ge n c y,  t he  i de ntit y  of  t he  test 
article ca n be re veale d b y scratc hi n g t his secti o n of t he la bel. T he 2- part la b el will c o ntai n 
at least t he f oll o wi n g i nf or mati o n: 
Pr ot oc ol G D C- 6 9 5- 0 0 1 
Kit N o.: 
S u bject N o: _ _ _ _ _ _ _ _ _ 
I nitials: _ _ _ _ _ _ _ _ _ 
C o nte nts: G D C 6 9 5 or Dicl ofe nac S o di u m Gel, 3 % or Ve hicl e Gel. 
A p pl y as dir ecte d.
St ore at C o ntr olle d R o o m Te m perat ure 2 0 t o 2 5° C ( 6 8 t o 7 7° F). 
Kee p o ut of r eac h of c hil dre n. 
Ca uti o n: Ne w Dr u g - Li mite d b y U nite d States la w t o i n vesti gati o nal use.
Ma n ufact ur e d f or Ga ge De vel o p me nt C o m pa n y, L L C
A 2. 2  Ret ai ns
Eac h site will be re q uire d t o ra n d o ml y select res er ve sa m ples fr o m t he s hi p me nt of test 
articles. I nstr u cti o ns o n t he n u m ber of kits t o  select a n d h o w t o d o c u me nt t he kit n u m bers 
selecte d as res er ve sa m pl es will be i ncl u de d i n t he s hi p me nt. Eac h site will t he n st ore t he 
reser v e  sa m ples  u n der  c o n diti o ns  c o nsiste nt  wit h  pr o d uct la beli n g  a n d  i n  a n  area 
se gre gat e d fr o m t he ar ea w here t esti n g is co n d ucte d a n d wit h access li mite d t o a ut h orize d 
pers o n nel.  Eac h  r eser v e  sa m ple   s hall  be  retai n e d  f or  a  peri o d  of  at  l east  fi ve  years 
f oll o wi n g t he date o n w hic h t he a p plicati o n or s u p ple me ntal a p pli cati o n is a p pr o ve d, or, 
if  s uc h  a p plicati o n  or  s u p ple me ntal  a p plicati o n  is  n ot  a p pr o ve d,  at  least  fi ve  years 
f oll o wi n g  t he  dat e  of  c o m pleti o n  of  t he  bi oa vaila bilit y  st u d y  fr o m  w hi c h  t he  res er ve 
sa m ples were o btai ne d. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 4 of 5 9 
A 2. 3 Test Articl e St or a ge a n d Pre p ar ati o n
Test  article  s h o ul d  be  st ore d   at  c o ntr olle d  r o o m  te m perat ure  2 0  t o  2 5°  C  ( 6 8  t o  7 7°  F), 
e x c ursi o ns  per mitte d  bet wee n  1 5  t o  3 0°  C  ( 5 9  t o  8 6°  F),  i n  a  sec ure  area  acc or di n g  t o 
l ocal re g ulati o ns.
A 2. 4  Dis pe nsi n g Test Article
T he test article m ust be dis pe nse d o nl y t o st u d y s u bjects a n d o nl y at st u d y sites s pecifie d 
o n t he f or m F D A 1 5 7 2 b y a ut h orize d pers o n nel as re q uire d b y a p plica ble re g ulati o ns a n d 
g ui deli nes. 
A 2. 5 Test Articl e S u p pl y Rec or ds at St u d y Sites
It  is  t he  r es p o nsi bilit y  of  t he  i n vesti gat or  t o e ns ure  t hat  a  c urre nt  rec or d  of  test  article 
dis p ositi o n is mai ntai ne d. Rec or ds or l o gs m ust c o m pl y wit h a p plica bl e re g ul ati o ns a n d 
g ui deli nes, a n d s h o ul d i n cl u de: 
A m o u nt recei ve d pl ace d i n st ora ge area.
A m o u nt c urre ntl y i n st ora ge area.
La b el I D n u m ber or bat c h n u m ber. 
Dates  a n d  i nitials  of  t he  pers o n  res p o nsi bl e  f or  eac h  pr o d u ct  i n ve nt or y 
e ntr y/ m o ve m e nt. 
A m o u nt  dis pe nse d  t o  a n d  ret ur ne d  b y eac h  s u bject,  i ncl u di n g  u ni q ue  s u bject 
i de ntifiers. T he t u bes will be  wei g he d pri or t o bei n g dis pe nse d a n d als o aft er t he y 
are r et ur ne d.
A m o u nt tra nsferre d t o a n ot her ar ea f or dis pe nsi n g or st ora ge. 
N o n-st u d y dis p ositi o n (e. g ., l ost, waste d, br o ke n). 
A m o u nt ret ur ne d t o S p o ns or. 
A m o u nt destr o ye d at st u d y site, if a p plica ble.
Retai n sa m ples se nt t o t hir d part y f or bi oa v aila bilit y/ bi oe q ui vale n ce.
will pr o vi de f or ms t o facilitate i n ve nt or y c o ntr ol if t he staff at t he st u d y site d oes n ot 
ha ve a n esta blis he d s yst e m t hat meets t hese re q uire me nts.
A 2. 6  D ose M o dific ati o ns 
D osi n g  m o dificati o ns  s h o ul d  be  n ote d  o n t he  s u bject  diar y  a n d  d oc u me nte d  i n  t he 
s u bject’s C R F.
A 2. 7  D oc u me nt ati o n of A p plic ati o n a n d C o m pli a nce 
S u bjects will be i nstr ucte d t o d oc u me nt t he a p plicati o n of test article a n d a n y misse d or 
hel d d oses o n t he s u bject diar y. 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 5 of 5 9 
A 2. 8  Ret ur n a n d Destr ucti o n of Test Article S u p plies
At t he c o m pleti o n or t er mi nati o n of t he st u d y, all u n use d a n d/ or partiall y use d test articl es 
m ust  be  ret ur ne d  b y  a  tracea ble  met h o d.  Al l  missi n g  t u bes  m ust  be  e x plai ne d  o n  t he 
c o m plete d Test Article Acc o u nta bilit y L o g. T he i n vesti gat or m ust kee p t he ori gi nal La b el 
pa ges  a n d  Test  Article  Acc o u nt a bilit y  L o g  i n  t he  site  st u d y  file.  P h ot oc o pies  of  t h e 
ori gi nal  Test  Article  Acc o u nt a bilit y  L o g  a n d  La bel  pa ges  will  be  ke pt  wit h  t he  st u d y 
rec or ds at  . All s hi p me nt of ret ur ne d t est article m ust be la bele d wit h t he i n vesti gat or’s 
na me, a d dress, a n d t he pr ot oc ol n u m ber. R et ur n all test articles i n t h e ori gi nal c o ntai ners 
b y a tr acea ble mea ns (e. g., 2- da y Fe d E x s hi p pi n g) t o: 
U p o n  recei pt  of  t he  test  articles,  a  S p o ns or  re prese ntati ve  will  perf or m  a  fi nal 
rec o nciliati o n.  
will be n otifie d of a n y missi n g test article.

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 6 of 5 9 
A P P E N DI X 3 
P R O T O C O L A M E N D M E N T S
P R O T O C O L A M E N D M E N T # 1
D ate of A me n d me nt: J a n u ar y 2 6, 2 0 1 7 
S u m m ar y:
T he pr ot oc ol was a me n d e d as f oll o ws: 
1.  U p date d  sec o n d  si g nat or y  f or  Ga ge  De vel o p me nt,  L L C  o n  pr ot o c ol  a p pr o val 
pa ge.
2.  
Was h o uts a n d pr o hi biti o n of oral ster oi d us e was c ha n ge d t o s yste mic ster oi d use. 
3. T he  descri pti o n  of  A Ks  was  m o difie d  i n   e x cl usi o n  criteri o n  # 4  gi ve n  t hat  a  fe w 
sites ha d iss ues wit h t he la n g u a ge p ertai ni n g t o “ m at-li ke”.
4. Re m o ve d “ A L A- P D T” fr o m e x cl usi o n crite ri o n # 1 7 gi ve n t hat it c o nflicts a n d/ or 
is re d u n da nt t o e x cl usi o n criteri o n # 1 3. 
5. I ns erte d  defi niti o n  f or  w hat  is  mea nt  b y   “t wice  dail y”  ot h er  t ha n  o nce  i n  t he 
m or ni n g  a n d  o nce  i n  t h e  e ve ni n g  b y  i ns erti n g  “(e. g.,  a p pr o xi matel y  8- 1 2  h o urs 
a part)” i n t he test article a p plicati o n secti o n of t he pr ot oc ol ( Secti o n 6).
6.  A defi niti o n of b al d scal p was a d de d as a f o ot n ote t o i ncl usi o n criteri o n # 4 i n t he 
s y n o psis a n d Secti o n 5. 1. 1 as well as i n s che d ule of e ve nts a n d was a d de d i n t he 
te xt of Secti o n 6. 2 (I nstr uctio ns f or Use a n d A p plicati o n).
S P E CI FI C  C H A N G E S: S pecific  c h a n ges  t o  t he  pr ot oc ol  are  liste d  b el o w;  ne w  or 
re vise d  secti o ns  are  i n cl u de d  (A d de d  text  h as  bee n b ol de d & del ete d  text  h as  bee n 
re dli ne d). Mi n or  t y p o gra p hical  err ors,  gra m m a tical,  a n d  w or di n g  c h a n ges  ar e  n ot 
i ncl u de d i n t his secti o n. 
Secti o n # / N a me
Re vise d Te xt
I n cl usi o n Criteri o n 
# 4
4.  
Has a cli nical dia g n osis of acti nic kerat oses wit h at least 
fi ve ( 5) a n d n o m ore t ha n te n (1 0 ) cli nicall y t y pi cal, visi ble, or 
pal pa ble,  discret e,  n o n h y per kerat otic,  n o n h y p ertr o p hic,  A K 
lesi o ns,  eac h  at  least  4  m m  i n  dia meter,  c o nt ai ne d  wit hi n  a 
c o nti n u o us 2 5 c m 2 treat me nt area l ocate d o n t he face (e x cl u di n g 
ears) or bal d scal p.
E x cl usi o n Criteria 
#s 4, 1 4, a n d 1 7 
4. 
S u bject  has  h y p er k erat otic ,  h y pertr o p hic  (i. e.,  Gra de  3 
A Ks), or lar ge mat-li ke A Ks of a n y Gr a de (e. g., A K > 1 c m 2 i n 
size) wit hi n t he treat me nt area.
1 4.  
Has  use d  oral s yste mic c ortic oster oi d  t hera p y (i ncl u des 
i ntr a m usc ul ar a n d i ntr a- artic ul ar a d mi nistr ati o n), i nterfer o n, 
c yt ot o xic  
dr u gs,  i m m u n o m o d ulat ors,  i m m u n os u p pressi ve 
t hera pies,  or  reti n oi ds  wit hi n  o ne  m o nt h  pri or  t o  t he  Bas eli ne 
Visit.
1 7.  
Has  ha d  der mat ol o gic  pr oce d ures  or  s ur geries  s uc h  as: 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 7 of 5 9 
laser  res urfaci n g,  P U V A  ( Ps orale n  +  ultra vi olet  A)  t hera p y, 
ultra vi olet B ( U V B) t hera p y, A L A- P D T, or der m a brasi o n wit hi n 
t he selecte d treat me nt area (face or bal d scal p) wit hi n si x m o nt hs 
pri or t o t he Bas eli ne Visit.
Secti o n 6. 2 
I nstr u cti o ns f or 
Use a n d 
A p plicati o n
S u bjects  will  be  i nstr uct e d  t o  a p pl y  t he  t est  article  t wice  dail y, 
o nce  i n  t he  m or ni n g  a n d  o nce  i n  t he  e ve ni n g 
(e. g., 
a p pr o xi m atel y 8- 1 2 h o urs a p art) , f or 6 0 da ys  t o t he e ntire 2 5 
c m 2 treat me nt  area  (t he  face  [e x cl u di n g  t he  ears]  or  t he  bal d 
scal p). S u bjects will be i nstr ucte d t o use t he p h ot o gra p h a n d t he 
“s u bject  s pecific”  te m plate  of  t heir  2 5  c m 2 treat me nt  area 
pr o vi de d  t o  t he m  at  Baseli ne  i n or der  t o  hel p  e ns ure  pr o p er 
a p plicati o n  of  t he  test  article.  Test  article  ma y  b e  a p plie d  wit h 
t he fi n gerti ps. N or mall y 0. 5 gra ms of gel is use d o n eac h 2 5 c m2
treat me nt area (e. g., sli g htl y s maller t ha n t he size of a di me; see 
A p pe n di x  1)  a n d  a p plie d  as  a  t hi n  fil m  t o  t he  e ntire  treat me nt 
area a n d r u b be d u ntil t he gel is n o l o n ger visi ble as i nstr ucte d b y 
t he  i n vesti gat or  or  site  staff.  I m me diatel y  after  a p plicati o n,  t he 
ha n ds s h o ul d be t h or o u g hl y w as h e d. S u bjects will be ca uti o ne d 
t o a v oi d a p pl yi n g t he gel near t he e yes, n ostrils, a n d m o ut h. T he 
test  article  s h o ul d  be  left  o n t he  s ki n  f or  a  mi ni m u m  of  f o ur 
h o urs  pri or  t o  was hi n g.  Treat me nt   s h o ul d  c o nti n ue  f or  t he  f ull 
treat me nt  c o urs e  e v e n  if  all  A Ks  a p pear  t o be  g o ne.  T he  st u d y 
staff  s h o ul d  de m o nstrate  t he  pr o per use  of  t he  test  article  usi n g 
t he ve hicle gel pr o vi d e d f or s u bject trai ni n g. See A p pe n di x 1 f or 
t he c o m plete S u bject I nstr ucti o ns.
8. 1 Pr o hi bite d 
Me dicati o ns or 
T hera p y
Pr o hi bite d me dicati o ns or t hera pies d uri n g t he st u d y i ncl u de: 
T o pical pr o d uct ot her t h a n t he as si g n e d treat me nt (i ncl u di n g 
m oist urizers,  s u n  scree n,  crea ms,  oi nt me nts,  l oti o ns, 
p o w ders,  or  gels  of  a n y  ki n d  a n d  ne w  bra n ds  of  ma ke- u p) 
wit hi n t he selecte d treat me nt area wit hi n o ne da y pri or t o t he 
Baseli ne Visit.
T o pical  me dicati o ns:  c ortic oste r oi ds,  al p ha  h y dr o x y  aci ds 
(e. g., gl yc olic aci d, lacti c aci d, et c. > 5 %), beta h y dr o x y aci d 
(salic yli c  aci d  > 2 %),  urea  > 2 %,  5-fl u or o uracil,  dicl ofe nac, 
i mi q ui m o d, i n ge n ol me b utate, A LA or prescri pti o n reti n oi ds 
(e. g., tazar ote ne, a d a pale ne, treti n oi n), O T C pro d ucts la bele d 
as scr u bs of a n y ki n d w hic h are use d t o s m o ot h t he s ki n (as 
t he y c o ntai n s o me f or m of e xf oliant s uc h as n ut s h ells, c offee 
gr o u n ds,  p ol y mer  particles,  etc.)  wit hi n  t he  select e d 
treat me nt area (face or b al d scal p) wit hi n o ne m o nt h pri or t o 
t he Bas eli ne Visit.
Cr y o destr u cti o n  or  c h e m o de str ucti o n,  c uretta ge,  P D T, 
s ur gical  e x cisi o n,  or  ot her  treat me nts  f or  A K  wit hi n  t he 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 8 of 5 9 
selecte d treat me nt area (face or bal d scal p) wit hi n o ne m o nt h 
pri or t o t he Bas eli ne Visit.
S yste mic
oral  
c ortic oster oi d  
t hera p y 
(i ncl u des 
i ntr a m usc ul ar  a d mi nistr ati o n,  see  Secti o n  8. 2  f or 
g ui d a nce  re g ar di n g  i ntr a- artic ul ar  c ortic oster oi ds) ,
i nterfer o n,  
c yt ot o xic  
dr u gs,  
i m m u n o m o d ulat ors, 
i m m u n os u p pressi ve t hera pies, or reti n oi ds wit hi n o ne m o nt h 
pri or t o t he Bas eli ne Visit.
Oral  is otreti n oi n  wit hi n  si x  m o nt hs  pri or  t o  t he  Baseli ne 
Visit.
C he mical  peels,  i ncl u di n g  b ut  n ot  li mite d  t o  al p ha h y dr o x y 
aci d,  beta h y dr o x y  aci d,  bic hl or o acetic  aci d,  tri c hl or oacetic 
aci d,  a n d  p h e n ol  wit hi n  t he  selecte d  treat me nt  area  (face  or 
bal d scal p) wit hi n si x m o nt hs pri or t o t he Baseli ne Visit.
Der mat ol o gic  pr oce d ures  or  s ur geries  s uc h  as:  laser 
res urfaci n g,  P U V A  t hera p y,  U V B  t hera p y,  A L A- P D T,  or 
der ma brasi o n wit hi n t he selecte d treat me nt area (face or bal d 
scal p) wit hi n si x m o nt hs pri or t o t he Bas eli ne Visit.
Areas treat e d wit h t he t est artic le s h o ul d n ot b e c o vere d wit h 
a n y t y p e of ba n d a ge or o ccl usi ve dressi n gs.
Secti o n 8. 2 
All o we d 
Me dicati o ns a n d 
T hera pies
T he use of a n y of t he f oll o wi n g all o we d me dicati o ns or t hera pies 
s h o ul d be d oc u me nte d i n t he s u bject’s C R F. 
A n y me dicati o ns n ot i nte n de d or be neficial f or t he treat me nt of 
A Ks ma y be use d u nless s pecificall y e xcl u de d or pr o hi bite d b y 
t his  pr ot oc ol  (see  Secti o n 8. 1:  Pr o hi bite d  Me dicati o ns  or
T hera pies a b o ve). 
N O T E: I deall y, treat me nt of A Ks at a b o d y site e x cl usi ve of 
t he H E A D s h o ul d be a v oi de d d uri n g t he st u d y p eri o d u nless
t he  treat me nt  is  dee me d  t o  be  a  material  me dical  necessit y 
f or t he s u bject b y t he i n vesti gat or. I n s uc h cases, t he O N L Y
all o we d treat me nts f or A Ks, at a n y b o d y site e xcl usi ve of t he 
H E A D,  are  f ocal  a n d  li mite d  treat me nt  t o  t he  A K  site  o nl y 
usi n g s ur gical e xcisi o n, cr y ot hera p y, a n d c uretta ge ± pi n p oi nt 
f ocal  electr o dessicati o n.  Use  of  a n y  ot her  treat me nt  met h o ds 
are is pr o hi bite d (see Secti o n 8. 1), as are t he treat me nt of a n y 
A Ks o n t he H E A D usi n g a n y met h o d.  
I n t he e ve nt t hat treat me nt of a n A K o n t he H E A D, b ut o utsi de 
t he  treat me nt  area,  is  dee me d  necessar y  b y  t he  i n vesti gat or, 
s uc h a pr oce d ure ma y o nl y be perf or me d after disc ussi o n a n d 
t he a p pr o val b y t he Me dical M o nit or.
I ntra nasal, i n hale d, a n d o p ht hal mic c ortic oster oi ds use d f or t he 
ma na ge me nt  of  aller gies,  p u l m o nar y  dis or ders,  or  ot her 
c o n diti o ns. 
A  si n gle  i ntr a- artic ul ar  c ortic oster oi d  i njecti o n  is  all o we d 

Pr o d uct Na me: G D C 6 9 5
Pr ot oc ol: G D C- 6 9 5- 0 0 1
S p o ns or Na me: Ga ge De vel o p me nt C o m pa n y, L L C
Pr ot oc ol Date: Ja n uar y 2 6, 2 0 1 7, v 2. 0
C O N FI D E N TI A L
Pa ge 5 9 of 5 9 
d uri n g  t he  st u d y.  A d diti o n al  tre at me nts  are  all o we d  o nl y 
wit h t he a p pr o v al of t he Me dic al M o nit or.
F o ot n ote t o 
i ncl usi o n criteri o n 
# 4 i n S y n o psis a n d 
Secti o n 5. 1. 1, 
f o ot n ote i n 
Sc he d ule of 
E ve nts, a n d te xt of 
Secti o n 6. 2 
(I nstr ucti o ns f or 
Use a n d 
A p plicati o n)
B al d sc al p f or t he p ur p oses of t his st u d y is a sc al p w here t he 
s u bject  h as  l ost  t he  m aj orit y  of  t heir  h air  ( w ell  o ver  5 0 %) 
wit hi n  t he  i nte n de d  2 5  c m 2 tre at me nt  are a  w here  t he  sc al p 
is:  a)  re a dil y  visi ble  a n d  2)  t he  n u m ber  of  t he  A Ks  i n  t he 
tre at me nt  a re a c a n  be  e asil y  see n  a n d  c o u nte d  b y  t he 
e v al u at or. It is als o i m p ort a nt t h at b ot h t he site a n d s u bject 
c a n re pe ate dl y i de ntif y t he tre at me nt a re a t o ass ure acc ur ate 
re pe at  t her a p y  b y  t he  s u bject  a n d  e v al u ati o n  b y  t he 
i n vesti g at or.