Clinical trial NCT02952898
Conditions: Actinic Keratosis
Keywords: solar keratoses
Sponsor: Balmoral Medical company
Start date: 2016-10-27; Completion date: 2017-09-06
Enrollment: 665 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This research study is being done to compare the safety and effectiveness of GDC 695 (test drug) against the currently marketed reference drug (diclofenac sodium gel, 3%) and to establish that these two drugs work better than placebo in the treatment of actinic keratosis.

Detailed description:

Arms: arm 1: GDC 695 gel applied topically as directed. arm 2: Diclofenac sodium gel, 3% applied topically as directed. arm 3: Vehicle gel applied topically as directed.
Interventions: intervention 1: GDC 695 intervention 2: Diclofenac Sodium Gel, 3% intervention 3: Vehicle gel
Intervention descriptions: intervention 1: GDC 695 is a topical gel. intervention 2: Diclofenac sodium gel, 3% is an FDA-approved drug. intervention 3: Vehicle topical gel contains 0.0% of active drug and is color matched to the other two active test drugs.

Protocol documents:
Prot_000.pdf: 
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. 

SAP_001.pdf: 
GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 1 of 16 
STATISTICAL ANALYSIS PLAN 
Title:
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
Protocol Number:
GDC-695-001
Sponsor:
Gage Development Company, LLC
Date:
14MAR2017
Status:
v1.0


GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 2 of 16 
TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................... 2 
GLOSSARY OF TERMS ................................................................................................... 3 
1 
INTRODUCTION ...................................................................................................... 4 
2 
PURPOSE OF THE ANALYSES .............................................................................. 4 
3 
STUDY OBJECTIVES AND ENDPOINTS .............................................................. 4 
4 
STUDY DESIGN........................................................................................................ 4 
5 
STUDY SCHEDULE OF EVENTS ........................................................................... 6 
6 
DEFINITIONS ............................................................................................................ 8 
7 
CLINICAL EVALUATIONS ..................................................................................... 8 
7.1 
Efficacy Measurements ........................................................................................ 8 
7.1.1 
AK Lesion Evaluation and Counting ............................................................ 8 
7.2 
Safety and Baseline Measurements ...................................................................... 8 
7.2.1 
Adverse Events ............................................................................................. 8 
7.2.2 
Local Skin Reactions Assessments ............................................................... 9 
7.2.3 
Dermatologic Exam ...................................................................................... 9 
7.2.4 
Laboratory Tests ........................................................................................... 9 
7.2.5 
Prior/Concomitant Medications and Concurrent Therapies/Procedures....... 9 
8 
STATISTICAL METHODS ....................................................................................... 9 
8.1 
General Considerations ........................................................................................ 9 
8.2 
Analysis Populations .......................................................................................... 10 
8.2.1 
Safety Population ........................................................................................ 10 
8.2.2 
mITT Population ......................................................................................... 10 
8.2.3 
PP Population .............................................................................................. 10 
8.3 
Methods for Handling Missing Data .................................................................. 10 
8.4 
Subject Disposition ............................................................................................ 11 
8.5 
Screening and Baseline Assessments ................................................................. 11 
8.5.1 
Demographic and Baseline Characteristics ................................................ 11 
8.5.2 
Medical History .......................................................................................... 11 
8.5.3 
Prior Medications ........................................................................................ 11 
8.6 
Efficacy Analyses ............................................................................................... 11 
8.6.1 
Primary Efficacy Analyses ......................................................................... 11 
8.7 
Dosing Compliance and Test Article Exposure ................................................. 12 
8.8 
Safety Analyses .................................................................................................. 13 
8.8.1 
Adverse Events ........................................................................................... 13 
8.8.2 
Local Skin Reactions .................................................................................. 13 
8.8.3 
Urine Pregnancy Tests ................................................................................ 13 
8.8.4 
Concomitant Medications and Concurrent Therapies/Procedures .............. 13 
8.9 
Sample Size ........................................................................................................ 13 
8.10 
Protocol Deviations ........................................................................................ 13 
8.11 
Interim Analysis ............................................................................................. 14 
8.12 
Subgroup Analyses ......................................................................................... 14 




GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 4 of 16 
1
INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the planned statistical analyses to be 
performed for data from Protocol GDC-695-001, “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.”  
This SAP was created using Clinical Protocol GDC-695-001 Version 2.0 dated 
26JAN2017, and the Electronic Case Report Forms (eCRF) Version 1.0 dated 
14Oct2016.
2
PURPOSE OF THE ANALYSES 
The purpose of this SAP is to outline the planned analyses to be completed to support the 
Clinical Study Report (CSR) for Protocol GDC-695-001.  Any post-hoc or unplanned 
analyses not identified in this SAP will be clearly identified in the CSR. 
3
STUDY OBJECTIVES AND ENDPOINTS 
The objectives of the study are to evaluate the safety and therapeutic equivalence of GDC 
695 to Diclofenac Sodium Gel, 3% and to establish the superiority of the efficacy of these 
two products over the vehicle gel in the treatment of actinic keratoses (AK). 
The primary efficacy endpoint is the proportion of subjects in the PP population with 
treatment success (“Complete Clearance”) at Day 90 (30 days after completion of 60
days of treatment). Complete Clearance is defined as 100% clearance of all AK lesions 
(having a count of zero AKs) in the 25 cm2 treatment area (face or bald scalp) at the Day 
90 visit.
Safety endpoints will include assessment of the severity and frequency of Adverse Events 
(AEs) and Local Skin Reactions (LSRs). 
4
STUDY DESIGN 
This is a multicenter, randomized, double-blind, placebo-controlled, parallel group 
comparison study of GDC 695 and Diclofenac Sodium Gel, 3% (Fougera) in subjects 
with AKs on the face or bald scalp. Approximately 600 subjects with at least five but no 
more than 10 clinically typical, visible or palpable, discrete, nonhyperkeratotic, 
nonhypertrophic, AK lesions, each at least 4 mm in diameter, contained within a 
continuous 25 cm2 treatment area located on the face (excluding the ears) or the bald 
scalp who fulfill the inclusion/exclusion criteria will be enrolled at approximately 28 
sites. 
Subjects will be randomized to one of three treatment groups on a 1:1:1 basis as follows: 
x
GDC 695 (Gage) (diclofenac sodium gel, 3%) 
x
Diclofenac Sodium Gel, 3% (Fougera) (Reference Product) 
x
Vehicle gel (Gage) 


GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 5 of 16 
All subjects will be instructed to apply the assigned test article to the entire 25 cm2
treatment area (face [excluding ears] or bald scalp) identified by the investigator at Visit 
1. The assigned test article will be applied twice daily, once in the morning and once in 
the evening, for 60 days to the entire 25 cm2 treatment area. The study will consist of a 
Screening/Baseline Visit, telephone calls at Day 15 and at Day 45, and follow-up visits at 
Day 30, Day 60, and Day 90 (30 days after completion of 60 days of treatment). 






GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 8 of 16 
6
DEFINITIONS
x
End of Treatment (EOT): Visit 5/Day 60 
x
End of Study (EOS):  Visit 6/Day 90 or Early Termination Visit 
x
Study Day: The study day is the day of study relative to the date of randomization 
(Baseline visit/Day 1). 
Study Day = follow-up visit date – randomization date + 1 
x
Baseline: The baseline assessment is defined as the last non-missing measurement 
collected at Baseline visit prior to the test article application.  
7
CLINICAL EVALUATIONS 
7.1
Efficacy Measurements 
7.1.1
AK Lesion Evaluation and Counting 
AK lesion counts will be performed at Baseline, Day 60/EOT, and Day 90/EOS. At the 
Baseline Visit (Visit 1) all AK lesions in the 25 cm2 Treatment Area, independent of size, 
will be identified, counted, recorded on the transparency, and measured for size (i.e., 
diameter). The number and location of AK lesions to be treated that are ≥4 mm in diameter 
will also be documented at the Baseline Visit. At Day 60/EOT and Day 90/EOS, the 
number of total AK lesions, independent of size, in the 25 cm2 Treatment Area will be 
counted including Baseline AKs and new AKs; a new AK is defined as a lesion that was 
not present at Baseline.
The AK clearance rate within treatment area for a subject at post-baseline follow-up
visits will be calculated as follows: 
{1 – [
͓஺௄௦௔௧௙௢௟௟௢௪ି௨௣
͓஺௄௦௔௧஻௔௦௘௟௜௡௘]} * 100. 
Therefore, if the AK count at follow-up visits is 0, the clearance rate will be 100%, i.e., 
complete clearance of AK lesions. 
7.2
Safety and Baseline Measurements 
7.2.1
Adverse Events 
An AE is defined as any untoward medical occurrence associated with the use of a drug 
in humans, whether or not considered drug related.  A treatment emergent AE (TEAE) is 
defined as an AE that started on or after the date if the first dose of test article. 
Serious adverse events (SAE) are defined as an AE or suspected adverse reaction that in 
the opinion of either the Investigator or Sponsor results in death, is life-threatening, 
requires inpatient hospitalization or prolongation of existing hospitalization, results in 
persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or is a congenital anomaly/birth defect, or important medical events 
defined in the protocol.


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Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 9 of 16 
The severity of an AE will be recorded as mild, moderate or severe.  The relationship 
between an AE and the test article will be classified as related, possibly related or not 
related.  The AE outcome will be specified as not recovered/resolved, recovered/resolved, 
recovered/resolved with sequelae, recovering/resolving, fatal, or unknown. 
7.2.2
Local Skin Reactions Assessments 
At Baseline, Day 30 follow-up, Day 60/EOT, Day 90/EOS, and Unscheduled Visits (if 
applicable), LSRs will be assessed in the 25 cm2 Treatment Area using a four-point 
ordinal scale of 0 = absent, 1= mild (slight, barely perceptible), 2=moderate (distinct 
presence) and 3 = severe (marked, intense) for the following:  
x
Erythema  
x
Dryness/flaking/scaling 
x
Burning/stinging 
x
Erosion/ulceration 
x
Edema 
x
Pain (within the last 24 hours) 
x
Pruritus (itching) (within the last 24 hours) 
These LSRs will be collected independently of AEs.  LSRs that require medical 
intervention (e.g. prescription medication) or extend beyond the 5 cm surrounding skin 
will be documented as AEs. 
7.2.3
Dermatologic Exam  
A dermatologic examination will be performed at the Baseline Visit.  
7.2.4
Laboratory Tests 
Urine Pregnancy Tests (UPTs) will be performed on all WOCBP at the Baseline Visit 
prior to randomization and at the Day 60/EOS visit. 
7.2.5
Prior/Concomitant Medications and Concurrent Therapies/Procedures 
Details of prior and concomitant medication use and concurrent therapies/procedures will
be collected for each subject. 
8
STATISTICAL METHODS 
8.1
General Considerations 
All statistical processing will be performed using SAS® Version 9.4 or higher, unless
otherwise stated.  For continuous variables, descriptive statistics will include the number 
of subjects with non-missing data (n), and mean, median, standard deviation, minimum 
and maximum values. For categorical variables, the number and percentage of subjects 
within each category will be presented. Subject data listings will be sorted by treatment 
group, study site and subject number. Summaries will be provided as specified below.   


GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 10 of 16 
8.2
Analysis Populations 
8.2.1
Safety Population 
The Safety population will include all randomized subjects who received at least one 
dose of the test article. 
8.2.2
mITT Population 
The modified Intent-to-Treat (mITT) population will include all randomized subjects who 
met all inclusion/exclusion criteria, applied at least one dose of test article, and returned 
for at least one post-baseline evaluation clinic visit (Visits 3, 5 and 6). Randomized 
subjects who are lost to follow-up after Visit 1, who return for the EOT visit but have not 
applied any test article, or who are found not to have met the eligibility criteria will be 
excluded from the mITT population.
8.2.3
PP Population 
The per-protocol (PP) population will include all randomized subjects who met all the 
following requirements: 
x
met inclusion/exclusion criteria,  
x
were compliant with the assigned test articles (applied at least 75% and no more 
than 125% of the expected (120) test article applications, did not miss more than 
10 consecutive scheduled applications and have no other evidence of material 
dosing noncompliance),  
x
completed the primary endpoint evaluation at Day 90 visit within the designated 
visit window (± 4 days), and 
x
had no protocol violations that would affect treatment evaluation. 
As exceptions to the above requirements, the following subjects will be included in the 
PP population as treatment failures if they met the mITT criteria: 
x
Subjects who are discontinued from the study due to worsening condition that 
requires alternate or supplemental therapy for the treatment of AK,
x
Subjects who are discontinued early from the study due to lack of treatment effect 
after completing at least four weeks of treatment.
8.3
Methods for Handling Missing Data 
If AK lesion counts are missing at post-baseline visits, depending on the reason for the 
early discontinuation, the following rules will be applied: 
x
For subjects who are discontinued prematurely due to worsening condition that 
requires alternate or supplemental therapy for the treatment of AK, or who are 
discontinued prematurely after completing at least four weeks of treatment due to 
lack of treatment effect, they will be included in the mITT and PP populations 
and considered as treatment failures.  
x
For subjects who are discontinued prematurely for any other reasons, Last 
Observation Carried Forward (LOCF) imputation will be used to impute the 
missing data. They will be included in the mITT population, but excluded from 
the PP population.   




GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 12 of 16 
Subjects who discontinued early from the study due to lack of treatment effect after 
completing at least four weeks of treatment or who worsen and require alternate or 
supplemental therapy will be included in the PP and the mITT populations as treatment 
failures (non-responders). For subjects who are discontinued prematurely for any other 
reasons, LOCF imputation will be used to impute missing data in the mITT population. 
Test for bioequivalence of test and reference treatments 
To establish bioequivalence for the proportion of subjects with treatment success, the 
following hypotheses will be tested in the PP population: 
H0: πT – πR < -0.2 or πT – πR > 0.2  
HA: -0.2 ≤πT – πR ≤0.2
, where πT is the proportion of subjects with treatment success in test treatment group 
(GDC 695 (diclofenac sodium gel, 3%)) and πR is the proportion of subjects with 
treatment success in reference treatment group (Diclofenac Sodium Gel, 3% (Fougera)). 
The null hypothesis, H0, is rejected with a type I error (alpha) of 0.05 (two one-sided 
tests) if the estimated 90% Wald’s confidence interval with Yate’s continuity correction 
for the difference of the success rates between test and reference treatment groups (πT –
πR) is contained within the interval [-0.2, 0.2]. Rejection of the null hypothesis supports 
the conclusion of equivalence of the test and reference treatments. 
This analysis will be repeated for mITT population as a supportive analysis. 
Test for superiority of each active treatment over vehicle treatment 
To establish that the study is sufficiently sensitive to detect the difference between 
treatments, two-sided, continuity-corrected chi-square tests with an alpha of 0.05 will be 
used to test the superiority of each active treatment group’s treatment success rate over 
that of the Vehicle treatment in the mITT population.  If any cells have an expected 
frequency of less than 5, then Fisher’s exact tests will be used instead.
This analysis will be repeated for PP population as a supportive analysis. 
8.7
Dosing Compliance and Test Article Exposure 
Test article compliance will be determined by the total number of test article applications 
verified from the data in the subject diaries. Compliant subjects are defined as those who 
apply at least 75% and no more than 125% of the expected (120) test article applications, 
did not miss more than 10 consecutive scheduled applications, and have no other 
evidence of material dosing noncompliance. 




GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 14 of 16 
8.11 Interim Analysis 
No interim analyses are planned. 
8.12 Subgroup Analyses 
No subgroup analyses are planned. 


GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 15 of 16 
List of Tables:
Demographic and Baseline Characteristics 
14.1.1  
Subject Disposition 
14.1.2  
Number of Subjects by Visit 
14.1.3.1 
Demographics (Safety Population) 
14.1.3.2 
Demographics (mITT Population)
14.1.3.3 
Demographics (PP Population) 
 
14.1.4.1 
Baseline AK Count and Treatment Area (Safety Population) 
14.1.4.2 
Baseline AK Count and Treatment Area (mITT Population)
14.1.4.3 
Baseline AK Count and Treatment Area (PP Population) 
14.1.5
Baseline Local Skin Reactions (Safety Population) 
Dosing Compliance and Exposure 
14.1.6.1 
Dosing Compliance and Test Article Exposure (Safety Population) 
14.1.6.2 
Dosing Compliance and Test Article Exposure (mITT Population) 
14.1.6.3 
Dosing Compliance and Test Article Exposure (PP Population) 
Efficacy Data 
14.2.1  
Complete Clearance Rates (PP and mITT Population)
14.2.2.1 
AK Counts and Clearance Rates (mITT Population) 
14.2.2.2 
AK Counts and Clearance Rates (PP Population) 
Safety Data 
14.3.1.1 
Summary of Adverse Events (Safety Population) 
14.3.1.2 
Treatment Emergent Adverse Events (Safety Population) 
14.3.1.3
Treatment Emergent Serious Adverse Events (Safety Population)
14.3.1.4 
Treatment Emergent Adverse Events by Severity (Safety Population) 
14.3.1.5 
 Treatment Emergent Adverse Events by Relationship to Test Article 
(Safety Population) 
14.3.1.6 
 Treatment Emergent Adverse Events Occurring within the Treatment Area 
(Safety Population)
14.3.2.1
Local Skin Reaction ‒ Erythema (Safety Population)
14.3.2.2
Local Skin Reaction ‒ Dryness/Flaking/Scaling (Safety Population) 
14.3.2.3
Local Skin Reaction ‒ Burning/Stinging (Safety Population) 
14.3.2.4
Local Skin Reaction ‒ Erosion/Ulceration (Safety Population) 
14.3.2.5
Local Skin Reaction ‒ Edema (Safety Population) 
14.3.2.6
Local Skin Reaction ‒ Pain (Safety Population) 
14.3.2.7
Local Skin Reaction ‒ Pruritus (Safety Population) 
14.3.3
Concomitant Medications (Safety Population) 


GDC 695 
Protocol GDC-695-001 
Gage Development Company, LLC 
Statistical Analysis Plan, v1.0 
Page 16 of 16 
List of Listings:
16.2.1             Subject Disposition 
16.2.2             Protocol Deviations 
16.2.3             Subjects Excluded from mITT or PP Population 
16.2.4.1 
Demographics 
16.2.4.2 
Eligibility 
16.2.4.3 
Medical History 
16.2.4.4 
Prior Medications 
16.2.5.1 
Test Article Dosing Compliance 
16.2.5.2           Test Article Dosing Interruption 
16.2.5.3 
Test Article Accountability 
16.2.6  
AK Counts and Clearance Rate 
16.2.7.1 
Adverse Events 
16.2.7.2 
Serious Adverse Events 
16.2.7.3 
Local Skin Reactions 
16.2.8
 Urine Pregnancy Test 
16.2.9.1
Concomitant Medications 
16.2.9.2 
Concurrent Therapies / Procedures