Conditions: Herpes Labialis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 4076
Healthy volunteers: no

Brief summary:
To compare safety and efficacy of Perrigo's antiviral drug product compared to an FDA approved antiviral drug product in the treatment of cold sores.

Detailed description:

Arms:
arm 1: acyclovir cream arm 2: acyclovir cream arm 3: Placebo cream

Interventions: intervention 1: Acyclovir 5 percent (Perrigo) intervention 2: Acyclovir 5 percent (Reference) intervention 3: Placebo cream
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol document:
Prot_000.pdf: 
 
 
NCT02265913 
 
04-22-2016 


 
 
 
A M ulti- C e nt er, D o u bl e- Bli n d, R a n d o miz e d V e hicl e- C o ntr oll e d, 
P ar all el- Gr o u p St u d y t o C o m p ar e P erri g o U K FI N C O ’s Ac ycl o vir 
Cr e a m, 5 % wit h Z O VI R A X ® ( Ac ycl o vir) Cr e a m 5 % , a n d b ot h Acti v e 
Tr e at m e nts t o a V e hicl e C o ntr ol i n Tr e at m e nt of R ec urr e nt H er p es 
Si m pl e x L a bi alis 
 
 
Pr ot oc ol N o.: P R G- N Y -1 4 -0 0 8  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o nfi d e nti al 
 
T h e c o nfi d e nti al i nf or m ati o n pr o vi d e d i n t his d oc u m e nt is f or us e b y p arti es dir ectl y i n v ol v e d 
i n t his i n v esti g ati o n.  B y acc e pti n g t his d oc u m e nt, y o u a gr e e t h at t h e i nf or m ati o n c o nt ai n e d 
h er ei n will n ot b e discl os e d t o a n y p ers o n n ot dir ectl y i n v ol v e d i n t his i n v esti g ati o n wit h o ut 
writt e n a ut h oriz ati o n fr o m P erri g o.
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 2 of 2 1 9






Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4  
 
6. 1  
St u dy M e dic ati o n ................................................................................................................ 2 7  
6. 2  
M e dic ati o n M a n a g e m e nt .................................................................................................... 2 8  
6. 2. 1  
L a b eli n g, P ac k a gi n g, Distri b uti o n, a n d R a n d o miz ati o n ............................................... 2 8  
6. 2. 2  
Pr oc e d ur e f or Br e a ki n g t h e Bli n d ................................................................................ 2 8  
6. 2. 3  
R et e nti o n S a m pl es ...................................................................................................... 2 9  
6. 2. 4  
St or a g e a n d St u dy M e dic ati o n Acc o u nt a bilit y ............................................................ 2 9  
7.  
A D V E R S E R E A C TI O N S ..................................................................................................... 3 0  
7. 1  
D evi ati o n fr o m t h e Pr ot oc ol f or I n di vi d u al S u bj ects ........................................................... 3 0  
7. 2  
D efi niti o ns ........................................................................................................................... 3 0  
7. 3  
Eliciti n g a n d R e p orti n g of A dv ers e E v e nts .......................................................................... 3 2  
7. 3. 1  
Ex p e dit e d R e p orti n g R es p o nsi biliti es of t h e St u dy C e nt er ......................................... 3 2  
7. 3. 2  
S u b mitti n g a n Ex p e dit e d S af et y R e p ort t o t h e I R B ..................................................... 3 3  
7. 4  
S A E & A Es R e q uiri n g Disc o nti n u ati o n of St u dy M e dic ati o n, i ncl u di n g Pr e g n a nci es ........... 3 4  
7. 4. 1  
Pr e g n a nc y .................................................................................................................... 3 5  
7. 5  
P ost St u dy A dv ers e Ev e nts .................................................................................................. 3 5  
7. 5. 1 
N o n -s eri o us A dv ers e E v e nts ........................................................................................ 3 5  
7. 5. 2  
S eri o us A dv ers e Ev e nts ............................................................................................... 3 6  
8.  
S T A TI S TI C AL C O N SI D E R A TI O N S ...................................................................................... 3 6  
8. 1  
G e n er al C o nsi d er ati o ns ....................................................................................................... 3 6  
8. 2  
A n al ysis P o p ul ati o ns ............................................................................................................ 3 6  
8. 3  
S a m pl e Siz e C o nsi d er ati o ns ................................................................................................ 3 7  
8. 4  
M e as ur es a n d A n al ysis ........................................................................................................ 3 8  
8. 4. 1  
Effic ac y E n d p oi nt a n d A n alysis .................................................................................... 3 8  
8. 4. 2  
S af et y E n d p oi nts a n d A n alysis ..................................................................................... 3 9  
8. 5  
C h ar act eristics of S u bj ects at Scr e e ni n g ............................................................................. 3 9  
9.  
C O N S E N T/ A S S E N T C O N SI D E R A TI O N S A N D P R O C E D U R E S ................................................ 4 0  
9. 1  
S u bj ect C o nfi d e nti ality ........................................................................................................ 4 1  
1 0.  C O N D U C T O F S T U D Y ...................................................................................................... 4 1  
1 0. 1  
C o m pl eti o n of St u dy ............................................................................................................ 4 1  
1 0. 2  
Pr ot oc ol A m e n d m e nts ........................................................................................................ 4 2  
1 1.  R E C O R D S M A N A G E M E N T ............................................................................................... 4 2  
1 1. 1  
D at a C oll ecti o n .................................................................................................................... 4 2  
1 1. 2  
S o urc e D oc u m e nts .............................................................................................................. 4 3  
1 1. 3  
Fil e M a n a g e m e nt at t h e St u dy Sit e ..................................................................................... 4 3  
1 1. 4  
R ec or ds R et e nti o n at t h e St u dy Sit e ................................................................................... 4 4  
1 2.  Q U ALI T Y C O N T R OL A N D Q U ALI T Y A S S U R A N C E ............................................................... 4 4  
1 2. 1 
M o nit or i n g .......................................................................................................................... 4 4  
1 2. 2  
A u diti n g ............................................................................................................................... 4 4  
1 3.  E T HI C S A N D R E S P O N SI B ILI T Y.......................................................................................... 4 5  
1 4.  U S E  O F I N F O R M A TI O N A N D P U BLI C A TI O N ..................................................................... 4 5  
1 5.  A P P E N DI C E S .................................................................................................................. 4 8
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
1 5. 1  
A p p e n dix A: St u dy P ers o n n el C o nt acts ............................................................................... 4 8  
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 5 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 5  
 
1 5. 2  
A p p e n dix B:  I nstr ucti o ns f or t h e S u bj ect ........................................................................... 4 9  
1 5. 3  
A p p e n dix D: P ac k a g e I ns ert Z ovir ax ® T o pic al Cr e a m .......................................................... 5 3  
1 6.  R E F E R E N C E S .................................................................................................................. 5 5
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 6 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 6  
 
S T U D Y S Y N O P SI S 
 
 
Titl e:  
A  M ulti -C e nt er,  D o u bl e -Bli n d,  R a n d o miz e d  V e hicl e -C o ntr oll e d,  P ar all el - Gr o u p  St u dy  t o 
C o m p ar e P erri g o U K FI N C O’s  Ac ycl ovir Cr e a m, 5 % wit h Z O VI R A X ® ( Ac ycl ovir) Cr e a m 5 %, 
a n d b ot h Activ e Tr e at m e nts t o a V e hicl e C o ntr ol i n Tr e at m e nt of R ec urr e nt H er p es L a bi alis  
St u d y 
M e dic ati o n : 
1.  Ac ycl o vir Cr e a m, 5 % , P erri g o  
2.  Z o vir ax ®  ( Ac ycl ovir) Cr e a m 5 %,  V al e a nt P h ar m ac e utic als  
3.  V e hicl e of Acycl o vir Cr e a m, 5 %,  P erri g o  
St u d y 
O bj ecti v es : 
T o  c o m p ar e t h e  s af et y  a n d  effic ac y  pr ofil e of P erri g o ’s Acycl o vir  Cr e a m ,  5 % t o Z ovir ax ®  
C r e a m 5 %  a n d  t o  d e m o nstr at e  t h e  bi o e q ui v al e nc e  t o  t h e  r ef er e nc e  pr o d uct  as  w ell  as 
s u p eri or effic acy of t h e t w o acti v e f or m ul ati o ns o v er t h at of t h e v e hicl e i n t h e tr e at m e nt of 
h er p es l a bi alis (c ol d s or es) i n a d ults a n d a d ol esc e nts 1 2  y e ars  of a g e a n d ol d er.  
St u d y D esi g n:  
S u bj ects  i n t his m ulti-c e nt er, d o u bl e- bli n d, r a n d o miz e d, v e hicl e-c o ntr oll e d, p ar all el- gr o u p 
bi o e q ui v al e nc e  st u dy  will  b e  a d mitt e d  i nt o  t h e  st u dy  o nl y  aft er  writt e n  i nf or m e d 
c o ns e nt/ ass e nt ( as a p plic a bl e) h as b e e n o bt ai n e d a n d aft er all i ncl usi o n/ excl usi o n crit eri a 
h a v e b e e n m et. M al e a n d f e m al e s u bj ects, 1 2 y e ars of a g e a n d ol d er, wit h r ec urr e nt h er p es 
si m pl ex l a bi alis will b e eli gi bl e f or e nr oll m e nt. 
St u d y 
P o p ul ati o n:  
 s u bj ects 1 2 y e ars of a g e a n d ol d er, w h o m e et t h e i ncl usi o n/ excl usi o n 
crit eri a, will b e e nr oll e d. 
D osi n g:  
S u bj ects will b e r a n d o miz e d 
 t o eit h er t h e t est pr o d uct, r ef er e nc e pr o d uct or 
v e hicl e tr e at m e nt gr o u p, r es p ectiv ely, a n d will a p pl y st u dy m e dic ati o n 5 ti m es d aily f or 4 
d a ys. 
 
   
St u d y Visits:  
T h e cli nic al tri al will c o ns ist of t h e f oll o wi n g visits:  
• 
Scr e e ni n g Visit - o nc e t h e s u bj ect m e ets i ncl usi o n/ excl usi o n crit eri a; t h e y will b e 
r a n d o miz e d a n d giv e n t h e st u dy m e dic ati o n. 
 
 
 
 
 
 
   
• 
Tr e at m e nt  D ays: 1 ( Visit 2),  2 ( Visit 3), 3 ( Visit 4), a n d 4 ( Visit 5)  
• 
F oll o w -u p  D ays : 5 ( Visit 6), 6 ( Visit 7), 7 ( Visit 8), 8 ( Visit 9), 1 0 ( Visit 1 0),  1 2 ( Visit 
1 1), 1 4 ( Visit 1 2 ), 2 1 ( Visit 1 3 ) 
• 
 
. If h e ali n g 
occ urs i n -b et w e e n sc h e d ul e d st u dy d ays, t h e s u bj ect s h o ul d r et ur n t o t h e cli nic as 
s o o n as p ossi bl e a n d n ot w ait till t h e n ext sc h e d ul e d visit .  
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 7 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 7  
 
Effic ac y 
Ass ess m e nts:  
T h e pri m ar y effic acy e n d p oi nt  will b e : Ti m e t o c o m pl et e h e ali n g of l esi o ns ( d efi n e d as l oss 
of cr ust a n d r e -e pit h eli aliz ati o n wit h or wit h o ut eryt h e m a, as ass ess e d by t h e i nv esti g at or, 
b as e d  o n  b ot h  cli nic al  o bs er v ati o n  a n d r evi e w  of  t h e  s u bj ect  di ary),  m e as ur e d  i n 
d a ys /h o urs fr o m  t h e ti m e of first d osi n g. 
 
 
 
 
S af et y  
Ass ess m e nts : 
T h e  i nci d e nc e  of  all  a dv ers e  ev e nts  r e p ort e d  d uri n g  t h e  st u dy  will  b e  s u m m ariz e d  by 
tr e at m e nt gr o u p.  E q ui v al e nc e of t h e t w o activ e f or m ul ati o ns wit h r e g ar d t o s af et y will b e 
e v al u at e d by c o m p ari n g t h e n at ur e, s ev erit y a n d fr e q u e nc y of t h eir a dv ers e e v e nt pr ofil es.  
I n a d diti o n, t h e fr e q u e nc y a n d distri b uti o n of a p plic ati o n sit e r e acti o ns of dr y li ps, cr ac k e d 
li ps,  d es q u a m ati o n,  dr y  s ki n,  b ur ni n g  s ki n,  pr urit us,  fl a ki n ess  of  s ki n,  a n d  sti n gi n g  of  t h e 
s ki n will b e s u m m ariz e d f or t h e t w o activ e f or m ul ati o ns. 
St atistic al 
M et h o ds : 
Effic ac y  
T h e pri m ar y effic ac y e n d p oi nt will b e t h e ti m e t o c o m pl et e h e ali n g of l esi o ns ( d efi n e d as 
l oss  of cr ust  a n d  r e-e pit h eli aliz ati o n  wit h  or  wit h o ut  eryt h e m a,  as  ass ess e d  by  t h e 
i nv esti g at or, b as e d o n b ot h cli nic al o bs erv ati o n a n d r e vi e w of t h e s u bj ect di ary), m e as ur e d 
i n d a ys/h o ur s fr o m t h e ti m e of first d osi n g. 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
E q ui v al e nc e of Cli nic al E n d p oi nt A n al ysis: T h e m e a n  ti m e t o c o m pl et e h e ali n g of t h e l esi o n 
f or t h e t est a n d r ef er e nc e tr e at m e nts will b e esti m at e d usi n g a n al ysis of V ari a nc e ( A N O V A) 
wit h tr e at m e nt a n d c e nt er as fix e d eff ects i n t h e m o d el. T h e 9 0 % c o nfi d e nc e i nt er v al f or 
t h e r ati o ( T est/ R ef er e nc e) of m e a n ti m e-t o-c o m pl et e h e ali n g will b e o bt ai n e d by Fi ell er’s 
m et h o d.  
A pl ot f or t h e r ati o ( T est/ R ef er e nc e) of m e a n ti m e -t o-c o m pl et e h e ali n g a n d ass oci at e d 9 0 % 
CI will b e pr es e nt e d.  
 
 
. F or t h e  ti m e t o c o m pl et e h e ali n g of l esi o n, t h e T est tr e at m e nt will b e 
c o nsi d er e d  t o  b e  t h er a p e utic all y  e q ui v al e nt  t o  t h e  R ef er e nc e  tr e at m e nt  if  t h e c alc ul at e d 
9 0 % c o nfi d e nc e i nt erv al of t h e r ati o of t h e m e a n s ( T est/ R ef er e nc e) f alls wit hi n t h e i nt er v al 
of 0. 8 0 t o  1. 2 5.  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 8 of 2 1 9




Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 9  
 
A B B R E VI A TI O N S 
 
A E  
A d v ers e E v e nt  
A N O V A  
A n al ysis of V ari a nc e  
C M H  
C oc hr a n – M a nt el – H a e nsz el t est  
C R F  
C as e R e p ort F or m  
D C F  
D at a Cl arific ati o n F or m  
F D A  
U S F o o d a n d Dr u g A d mi nistr ati o n  
G C P  
G o o d Cli nic al Pr actic e  
I C H 
I nt er n ati o n al C o nf er e nc e o n H ar m o niz ati o n 
I G A 
I n v esti g at or’s Gl o b al Ass ess m e nt 
I R B 
I nstit uti o n al R e vi e w B o ar d 
I T T 
I nt e nt t o Tr e at p o p ul ati o n 
mI T T  
M o difi e d I nt e nt t o Tr e at p o p ul ati o n  
L P N 
Lic e ns e d Pr actic al N urs e  
L V N 
Lic e ns e d V oc ati o n al N urs e  
N P  
N urs e Pr actiti o n er  
O T C  
O v er t h e C o u nt er  
P A  
P h ysici a n’s Assist a nt  
PI  
Pri nci p al I n v esti g at or  
P P  
P er Pr ot oc ol P o p ul ati o n  
R N  
R e gist er e d N urs e  
Rx  
Pr escri pti o n  
S A E  
S eri o us A d v ers e E v e nt  
S A P  
St atistic al A n al ysis Pl a n  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 0 of 2 1 9




Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 1 1   
 
 
 
 
2. 1  Effic ac y E n d p oi nts 
 
T h e pri m ar y effic acy e n d p oi nt will b e t h e  ti m e t o c o m pl et e h e ali n g of l esi o ns ( d efi n e d as 
l oss  of  cr ust  a n d  r e- e pit h eli aliz ati o n  wit h  or  wit h o ut  er yt h e m a,  as  ass ess e d  b y  t h e 
i n v esti g at or, b as e d o n b ot h cli nic al o bs er v ati o n a n d r e vi e w of t h e s u bj ect di ar y), m e as ur e d 
i n d a ys/ h o urs fr o m t h e ti m e of first d osi n g.  
 
 
 
 
 
2. 2  S af et y  
 
S af et y  of  t h e  t est  a n d  r ef er e nc e  pr o d ucts  will  b e  c o m p ar e d  b y  e v al u ati n g  t h e  n at ur e, 
s e v erit y a n d fr e q u e ncy of t h eir a d v ers e e v e nt pr ofil es.   
 
3.  
S T U D Y D E T AIL S 
 
3. 1  St u d y O v er vi e w 
 
S u bj ects  i n  t his  m ulti-c e nt er,  d o u bl e- bli n d,  r a n d o miz e d,  v e hicl e-c o ntr oll e d,  p ar all el- gr o u p 
bi o e q ui v al e nc e st u d y will b e assi g n e d 
 t o t est pr o d uct, r ef er e nc e pr o d uct, or 
v e hicl e, r es p ecti v el y. S u bj ects will a p pl y st u d y m e dic ati o n 5 ti m es d ail y f or 4 d a ys.  
 
 
3. 2  St u d y P o p ul ati o n 
 
  i m m u n oc o m p et e nt  m al es/f e m al es, ≥  1 2  y e ars  of  a g e   wit h  a cli nic al 
di a g n osis of n o n -lif e-t hr e at e ni n g r ec urr e nt h er p es si m pl ex l a bi alis w h o m e et t h e i ncl usi o n-
excl usi o n crit eri a, will b e e nr oll e d i n t h e m ultic e nt er st u d y. 
 
3. 3  St u d y D esi g n 
 
Scr e e ni n g Visit: 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
D uri n g Visit 1, o nc e t h e s u bj ect m e ets i ncl usi o n- excl usi o n crit eri a, t h e y will b e r a n d o miz e d 
a n d  gi v e n  t h e  st u d y  m e dic ati o n. 
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 2 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 1 2   
 
 
 
 
 
 
 
 
 
 
 
 
Tr e at m e nt Visits: 
 
S u bj ects will c o m e i n f or D a y 1 ( Visit 2) 
. At t his visit, 
t h e y  will  b e  q u esti o n e d  r e g ar di n g  o ns et  of  t h e  e pis o d e.  T h e  i n v esti g at or  will  i d e ntif y a 
t ar g et ar e a a n d m ar k it i n t h e s o urc e d oc u m e nt.  
 
Cli nic visits will t a k e pl ac e o n D a ys 2 ( Visit 3 ), 3 ( Visit 4) a n d  4 ( Visit 5). 
 
All  s u bj ects  m ust  b e  tr e at e d  wit h  t h e  st u d y  m e dic ati o n  f or  4  d a ys  e v e n  if  t h e  l esi o n  h as 
h e al e d b ef or e tr e at m e nt e n ds. 
 
F oll o w- u p visits: 
T h e s u bj ects will r et ur n t h eir st u d y m e dic ati o n o n D a y 5 ( Visit 6). 
 
S u bs e q u e nt f oll o w u p visits will t a k e pl ac e o n: 
 
 D a ys 6 ( Visit 7), 7 ( Visit 8), 8 ( Visit 9), 1 0 ( Visit 1 0) a n d 1 2 ( Visit 1 1) .  
 D a y 1 4 ( Visit 1 2) will h a v e a wi n d o w +/- 1 d a y (i. e. D a y 1 3- 1 5).  
 D a y 2 1 ( Visit 1 3 ) will h a v e a wi n d o w of +/ - 2 d a ys (i. e. D a y 1 9 - 2 3). 
 
 
 
 
 
N ot e:  
If t h e s u bj ect’s l esi o n h as h e al e d pri or t o 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
D a y 5 ( Visit 6), t h e s u bj ect will c o nti n u e t o a p pl y 
t h e  st u d y m e dic ati o n  as  pr o p os e d  f or  4  d a ys,  a n d  r et ur n  f or  all  st u d y Visits  u p  t o  D a y 5 
( Visit 6), w hic h will b e t h eir En d of St u d y Visit. 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 3 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 1 3   
 
 
If  t h e  l esi o n  is  h e al e d  aft er  D a y  5  ( Visit  6)  b ut  b ef or e  D a y  2 1  ( Visit  1 3),  t h e  s u bj ect  will 
r et ur n f or t h eir En d  of S t u dy visit as dir ect e d b y pr ot oc ol u p o n h e ali n g a n d will n ot h a v e t o 
c o nti n u e c o mi n g t o t h e cli nic f or t h e r e m ai ni n g st u d y visits. 
 
 
 
 
 
  
 
If  a  s u bj ect  arri v es  t o  t h e  cli nic  f or  a n  u nsc h e d ul e d  visit,  t h e  s u bj ect  will  g o  t hr o u g h  t h e 
s a m e  pr oc e d ur es  as  a  sc h e d ul e d  f oll o w- u p  d ay.  If  t h e  s u bj ect  h as  n ot  h e al e d b y   t his 
u nsc h e d ul e d  visit,  t h e  s u bj ect  will  r et ur n  t o  t h e  cli nic  f or  t h e  s u bs e q u e nt  pr e vi o usl y 
pl a n n e d f oll o w- u p visits.  
 
T h e  us e  of  t h e st u d y  m e dic ati o n  s h o ul d  b e  disc o nti n u e d  aft er  D a y  4;  h o w e v er  t h e 
i n v esti g at or will c o nti n u e t o m o nit or t h e l esi o n u ntil D a y 2 1 if n ot h e al e d b y t h e n.  
 
 
 
 
 
4.  
S EL E C TI O N A N D WI T H D R A W AL O F S T U D Y S U BJ E C T S  
 
4. 1  I ncl usi o n Crit eri a 
 
S u bj ects m ust  m e et all of t h e f oll o wi n g crit eri a: 
 
1.  I m m u n oc o m p et e nt  ( d efi n e d as   n ot  h a vi n g  u n d erl yi n g  dis e as e  a n d/ or  t h e 
a d mi nistr ati o n of i m m u n os u p pr ess a nt m e dic ati o n) m al e or n o n pr e g n a nt f e m al es, 1 2 y e ars 
of a g e a n d ol d er, wit h n o n -lif e-t hr e at e ni n g r ec urr e nt h er p es si m pl ex l a bi alis. 
2.  S u bj ects  m ust  h a v e  
  r ec urr e nc es  of  h er p es  si m pl ex  l a bi alis  p er  y e ar  f or  t h e 
p ast  
y e ars. 
a.  
 r ec urr e nc es pr ec e d e d b y r ec o g niz a bl e pr o dr o m al s y m pt o ms  
 
 
b.  
 pr o dr o m es f oll o w e d b y cl assic al l esi o ns.  
3.  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
S u bj ect  m ust  si g n  a n  I nstit uti o n al  R e vi e w  B o ar d  (I R B)  a p pr o v e d  writt e n  i nf or m e d 
c o ns e nt f or t his st u d y pri or t o st u d y r el at e d pr oc e d ur es b ei n g p erf or m e d.  S u bj ects u n d er 
t h e  l e g al  a g e  of  c o ns e nt  m ust  si g n  a n  I R B  a p pr o v e d  writt e n  i nf or m e d  c o ns e nt/ ass e nt  i n 
a d diti o n t o a p ar e nt or l e g all y a ut h oriz e d r e pr es e nt ati v e. 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 4 of 2 1 9




Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 1 5   
 
7.  R ec e nt m aj or c h a n g e i n i m m u n e s yst e m st at us t h at  c o ul d s eri o usl y aff ect t h e cli nic al 
m a nif est ati o ns  of  h er p es  si m pl ex  l a bi alis  a n d  n e e d  f or  tr e at m e nt  i n  t h e  o pi ni o n  of  t h e 
i n v esti g at or.  
8.  S u bj ects  wit h  k n o w n  or  s us p ect e d  hist or y  of  a  cli nic all y  si g nific a nt  s yst e mic  dis e as es 
(i. e., i m m u n ol o gic al d efici e nci es), u nst a bl e m e dic al dis or d ers (i. e., u nst a bl e di a b et es), lif e-
t hr e at e ni n g dis e as e or c urr e nt m ali g n a nci es.  
9.  S u bj ects wit h c urr e nt e pis o d e of h er p es si m pl ex l a bi als t h at is n ot c o m pl et el y h e al e d 
( O nc e  c urr e nt  l esi o n  is  h e al e d,  t h e  s u bj ect  m ay  r et ur n  f or  scr e e ni n g  a n d  e nr oll  i n  t h e 
st u d y.)  
1 0.  Exc essi v e f aci al h air ( e. g. b e ar ds, m o ust ac h es, etc.) t h at w o ul d i nt erf er e wit h t h e dir ect 
ar e a f or di a g n osis or ass ess m e nt of h er p es l a bi alis.  
1 1.  Pr es e nc e  of  a n y  ot h er  f aci al  s ki n  c o n diti o n  t h at  mi g ht  i nt erf er e  wit h  h er p es  l a bi alis 
di a g n osis, ass ess m e nt, a n d/ or h e ali n g a bilit y 
 
 
 
1 2.  Hist or y of h er p es k er atitis. 
1 3.  C o ntr ai n dic ati o n  t o  a ntivir al  t h er a p y or  k n o w n  h y p ers e nsiti vit y t o  a n y c o m p o n e nt  of 
ac ycl o vir t h er a p y. T his i ncl u d es s u bj ects w h o h av e a k n o w n h y p ers e nsitivit y t o a n y of t h e 
f oll o wi n g (i n a n y d os a g e f or m): Ac ycl o vir 
 
. 
1 4.  Hist or y of u nr es p o nsi v e n ess t o t o pic al ac ycl o vir t h er a p y. 
1 5.  Us e of  a n y pr escri pti o n or o v er t h e c o u nt er a ntivir als  
  pri or t o scr e e ni n g, 3 0 
d a ys pri or t o tr e at m e nt i niti ati o n a n d t hr o u g h o ut t h e tr e at m e nt a n d f oll o w u p p eri o ds of 
t h e st u d y.   
1 6.  P artici p ati o n  i n  a n y  ot h er  cli nic al  st u d y  or  w h o  h a v e  r ec ei v e d  tr e at m e nt  wit h  a n y 
i n v esti g ati o n al  dr u g  or  d e vic e wit hi n  3 0   d a ys  pri or  t o  scr e e ni n g.  If  t h e  i n v esti g ati o n al 
pr o d uct us e d i n t h e pri or cli nic al st u d y is b eli e v e d t o h a v e l asti n g eff ects b e y o n d 3 0 d a ys, 
t h e i n v esti g at or s h o ul d d e e m a n a p pr o pri at e w as h o ut o ut p eri o d pri or t o scr e e ni n g. 
1 7.  S u bj ects w h o h a v e pr e vi o usl y b e e n e nr oll e d i n t his st u d y.  
1 8.  S u bj ects w h o h a v e r ec eiv e d a n y l oc al m e dic ati o n, i ncl u di n g t o pic al c ortic ost er oi ds, i n 
t h e t ar g et ar e a t hr o u g h o ut t h e tr e at m e nt a n d f oll o w u p p eri o ds of t h e st u d y. 
1 9.  S u bj ects  w h o  h a v e  b e e n  tr e at e d  wit h  i m m u n os u p pr essi v e  t h er a p y 
   
 pri or t o D a y 1 ( Visit 2) st u d y visit f or i n dic ati o ns s uc h as: 
a.  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
T o pr e v e nt t h e r ej ecti o n of tr a ns pl a nt e d or g a ns a n d tiss u es ( e. g., b o n e m arr o w, 
h e art, ki d n e y, li v er). 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 6 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 1 6   
 
b.  T o  tr e at  a ut oi m m u n e  dis e as es  or  dis e as es  t h at  ar e  m ost  li k el y  of  a n 
a ut oi m m u n e  ori gi n  ( e. g.,  r h e u m at oi d  art hritis,  m ulti pl e  scl er osis,  m y ast h e ni a 
gr a vis,  s yst e mic  l u p us  er yt h e m at os us,  s arc oi d osis,  f oc al  s e g m e nt al 
gl o m er ul oscl er osis,  Cr o h n’s  dis e as e,  B e hc et’s  Dis e as e,  p e m p hi g us,  a n d 
ulc er ati v e c olitis). 
c. T o t r e at ot h er n o n- a ut oi m m u n e i nfl a m m at or y dis e as es.  
2 0.  S u bj ect  c o ns u m es  exc essi v e  alc o h ol,  a b us es  dr u gs,  or  h as  a  c o n diti o n  t h at  c o ul d 
c o m pr o mis e  t h e  s u bj ect’s  a bilit y  t o  c o m pl y  wit h  st u d y  r e q uir e m e nts  i n  t h e  i n v esti g at or’s 
o pi ni o n . 
 
2 1.  Us e of t a n ni n g b o ot hs, s u n l a m ps, s u n b at hi n g or exc essi v e ex p os ur e t o t h e s u n  
 
 fr o m i niti ati n g st u d y m e dic ati o n.  
 
2 2.  S u bj ects  usi n g  i m m u n osti m ul at ors  ( B C G,  l e v a mis ol e,  etc.),  d y e-li g ht  t h er a p y,  or 
ps or al e n t h er a p y 
 pri or t o st u d y m e dic ati o n i niti ati o n. 
 
2 3.  
 
  
 
2 4.  
. 
 
 
 
4. 3  Pr ec a uti o ns 
 
T h e f oll o wi n g pr ec a uti o ns ar e t o b e t a k e n d uri n g tr e at m e nt a n d f oll o w u p p eri o ds of t h e 
st u d y: 
1.  S u bj ects  s h o ul d  a v oi d  c o nt act  of  t h e  st u d y  m e dic ati o n  i nsi d e  t h e  e y es,  m o ut h,  a n d 
n os e. I n c as e of acci d e nt al ex p os ur e, ri ns e wit h pl e nt y of w at er. 
2.  S u bj ect s h o ul d b e t ol d t h at tr e at m e nt d o es n ot pr e v e nt t h e m fr o m b ei n g c o nt a gi o us.  
3.  S u bj ects s h o ul d a v oi d li p/ or al c o nt act wit h ot h er i n di vi d u als (i ncl u di n g kissi n g) d uri n g 
tr e at m e nt t o a v oi d tr a ns missi o n of i nf ecti o n.  
4.  T h e st u d y m e dic ati o n is n ot t o b e s h ar e d wit h a ny ot h er p ers o ns or us e d i n a n y ot h er 
m a n n er t h a n i nstr uct e d b y t h e cli nic.  
5.  
 
. 
6.  
 
   
7.  
 
8.  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 7 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 1 7   
 
 
  
  
 
 
9.   S u bj ects  s h o ul d  c o ns ult  t h e  i n v esti g at or  wit h  a n y  q u esti o ns  r e g ar di n g  c o nc o mit a nt 
m e dic ati o ns. 
1 0.  S u bj ects s h o ul d w as h h a n ds b ef or e a n d aft er a p pl yi n g st u d y m e dic ati o n.  
1 1.  
 
 
1 2.  
. 
1 3.  
 
 
   
1 4.  
 
  
1 5.  S u bj ects s h o ul d n ot e at or dri n k  
 pri or t o or aft er d osi n g t o a v oi d irrit ati o n 
a n d m ai nt ai n cl e a nli n ess of aff ect e d ar e a w h e n a p pl yi n g st u d y m e dic ati o n.  
1 6.  St u d y m e dic ati o n s h o ul d b e k e pt i n r o o m t e m p er at ur e at all ti m es  ( at or b el o w 2 5° C 
( 7 7° F);  exc ursi o ns  p er mitt e d  t o  1 5°  t o  3 0° C  ( 5 9°  t o  8 6° F))  a n d  k e pt  a w ay  fr o m  extr e m e 
h ot/c ol d  e n vir o n m e nts (i. e. l eft i n t h e c ar o n a h ot/c ol d d a y).  
1 7.  
 
 
 
 
5.  
P R O C E D U R E S 
 
5. 1  S u bj ect Scr e e ni n g a n d E nr oll m e nt 
 
T h e st u d y p ers o n n el will r e vi e w t h e I R B a p pr o v e d i nf or m e d c o ns e nt f or m a n d ass e nt f or m, 
as  a p plic a bl e, wit h e ac h s u bj ect a n d gi v e t h e s u bj ect a n o p p ort u nit y t o h a v e all q u esti o ns 
a ns w er e d  b ef or e  pr oc e e di n g.    T h e  c o ns e nt/ ass e nt  f or m  m ust  b e  si g n e d  b y  e ac h  s u bj ect 
a n d  wit n ess e d  b ef or e  t h e  s u bj ect  is  e nr oll e d  i nt o  t h e  st u d y.    A  c o p y  of  t h e  si g n e d 
c o ns e nt/ ass e nt will b e gi v e n t o e v er y p artici p a nt a n d t h e ori gi n al will b e m ai nt ai n e d wit h 
t h e p artici p a nt’s 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
st u d y r ec or ds.  S u bj ects u n d er t h e l e g al a g e of c o ns e nt m ust si g n a n I R B 
a p pr o v e d  writt e n  i nf or m e d  c o ns e nt/ ass e nt  i n  a d diti o n  t o  a  p ar e nt  or  l e g all y  a ut h oriz e d 
r e pr es e nt ati v e.  O nc e  a  s u bj ect  h as  b e e n  scr e e n e d  a n d  m e ets  t h e  i ncl usi o n/ excl usi o n 
crit eri a, s u bj ects will r ec ei v e t h e st u d y m e dic ati o n.  
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 8 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 1 8   
 
 
 
 
 
 
5. 2  Assi g n m e nt of S u bj ect N u m b er 
   
O nc e t h e s u bj ect h as c o ns e nt e d, m et i ncl usi o n/ excl usi o n crit eri a, t h e y will b e assi g n e d a 
s u bj ect n u m b er. T h e s u bj ect n u m b er will b e t a k e n fr o m t h e st u d y m e dic ati o n kit  dis p e ns e d 
t o t h e s u bj ect at e ac h sit e.  
 
5. 3  D e m o gr a p hics/ M e dic al Hist or y 
 
A d e m o gr a p hic  pr ofil e  a n d  c o m pl et e  m e dic al  hist or y  will  b e  r ec or d e d  pri or  t o  st arti n g 
st u d y  m e dic ati o n.    T h e  m e dic al  hist or y  will  i ncl u d e  a  c o m pl et e  r e vi e w  of  all  c urr e nt 
dis e as es a n d t h eir r es p ecti v e tr e at m e nts. 
 
 
5. 4  C o nc o mit a nt M e dic ati o ns 
 
C o nc o mit a nt  m e dic ati o ns  a n d  a n y  m e dic ati o ns  t a k e n 
  pri or  t o  si g ni n g 
i nf or m e d  c o ns e nt/ ass e nt  will  b e  r ec or d e d  as  pri or/c o nc o mit a nt  m e dic ati o ns  ( usi n g  t h eir 
g e n eric  n a m e,  if  k n o w n)  wit h  t h e  c orr es p o n di n g  i n dic ati o n.  T h e  m e dic ati o ns  t o  b e 
r ec or d e d  will  i ncl u d e  pr escri pti o n  a n d  o v er-th e -c o u nt er  ( O T C)  m e dic ati o ns  as  w ell  as 
di et ar y  s u p pl e m e nts.    All  m e dic ati o ns  t a k e n  o n  eit h er  a  r e g ul ar  or  “ pr n”  b asis,  i ncl u di n g 
vit a mi ns, as piri n a n d ac et a mi n o p h e n, s h o ul d b e r ec or d e d o n t his p a g e.  
 
5. 5  P h ysic al E x a mi n ati o n 
 
T h e  i n v esti g at or,  s u b-i nv esti g at or  or  a p pr o pri at el y  d el e g at e d  a n d  q u alifi e d  d esi g n e e  will 
p erf or m a bri ef p h ysic al ex a mi n ati o n o n Visit 1 ( Scr e e ni n g) a n d Visit 2 ( D a y 1). T h e ex a m 
will  i ncl u d e  E N T,   h e art,  l u n g,  a b d o m e n  e v al u ati o n  as  w ell  as  r ec or di n g  vit al  si g ns.    Vit al 
si g ns  ar e  t o  i ncl u d e  sitti n g  bl o o d  pr ess ur e,  or al  t e m p er at ur e,  h e art  r at e,  a n d  r es pir at or y 
r at e. 
 
5. 6  Uri n e Pr e g n a nc y T est 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
F e m al es of c hil d b e ari n g p ot e nti al ( excl u di n g w o m e n w h o ar e s ur gic all y st eriliz e d (v erifi e d 
t u b al li g ati o n or bil at er al o o p h or ect o m y or h yst er ect o m y) or p ost- m e n o p a us al f or at l e ast 
2 y e ars), i n a d diti o n t o h a vi n g a n e g ativ e uri n e pr e g n a ncy t est, m ust b e willi n g t o us e a n 
acc e pt a bl e  f or m  of  birt h  c o ntr ol  d uri n g  t h e  st u d y.  A n  i n v esti g at or  c o ul d  r e p e at  t h e 
pr e g n a ncy t est at a n y ti m e d uri n g t h e st u d y if t h er e is a n y s us pici o n or p ossi bilit y t h at t h e 
s u bj ect is pr e g n a nt. 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 9 of 2 1 9




Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 2 0   
 
 
At   D a y  1  ( Visit  2)  a n d at   e ac h  s u bs e q u e nt  visit, a p plic ati o n  sit e  r e acti o ns  s uc h  as 
dr y  li ps,  d es q u a m ati o n,  dr y n ess  of  s ki n,  cr ac k e d  li ps,  b ur ni n g  s ki n,  pr urit us , 
fl a ki n ess of s ki n a n d sti n gi n g o n t h e s ki n (if a n y) will b e  r ec or d e d.  
 
 
 
  
 
  
 
. 
 
 
 
S C O R E  
A S S E S S M E N T 
D E S C RI P TI O N 
0  
N o n e  
 
1  
Mil d  
 
2  
M o d er at e  
 
3  
S e v er e  
 
 
5. 8  St u d y M e dic ati o n Us e, a n d Di ar y I nstr ucti o ns  
 
At   t h e  Scr e e ni n g  Visit  ( Visit  1),  e ac h  s u bj ect  will  b e  scr e e n e d  f or  i ncl usi o n/ excl usi o n 
crit eri a. T h e s u bj ects w h o q u alif y will b e r a n d o miz e d a n d dis p e ns e d t h e st u d y m e dic ati o n 
al o n g wit h t h e di ar y i ncl u di n g t h e st u d y i nstr ucti o ns.  
 
 
 
  
 
T h e st u d y st aff will i nstr uct t h e s u bj ect h o w t o a p pl y t h e st u d y m e dic ati o n. 
 
 
  
 
 
 
 
Sit e R e acti o n  
D E S C RI P TI O N 
Dr y Li ps 
  
D es q u a m ati o n  
  
  
Dr y n ess of S ki n  
  
Cr ac k e d Li ps  
 
  
B ur ni n g s ki n  
  
Pr urit us  
  
Fl a ki n ess of S ki n  
  
Sti n gi n g of t h e s ki n  
  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 2 1 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 2 1   
 
 
.   
 
T h e st u d y st aff will als o i nstr uct t h e s u bj ect o n h o w t o c o m pl et e t h e di ar y . T h e s u bj ects will 
r ec or d t h e ti m e a n d d at e of e ac h a p plic ati o n a n d h e ali n g ti m e i n t h e di ar y. S u bj ects will b e  
as k e d t o r ec or d t h e st a g e of t h eir h er p es l esi o n as  w ell as r ec or d t h eir s y m pt o ms (i. e. p ai n, 
b ur ni n g,  sti n gi n g,  itc hi n g,  ti n gli n g,  etc.)  t wic e  a  d a y . 
 
 
 
 
T h e s u bj ect will b e i nstr uct e d t o bri n g t h e di ar y a n d st u d y m e dic ati o n wit h t h e m at all visits 
f or st aff r e vi e w of c o m pli a nc e. T h e st u d y st aff m ust c o nfir m t h at t h e s u bj ect is r ec or di n g all 
r el e v a nt i nf or m ati o n i n a pr o p er m a n n er. 
 
5. 9  Visit S p ecific Pr oc e d ur es 
 
T h e f oll o wi n g s ecti o ns o utli n e t h e pr oc e d ur es r e q uir e d at e ac h visit. 
 
5. 9. 1  
Scr e e ni n g Visit ( Visit 1) 
  
  
Pr os p ecti v e s u bj ects will visit t h e st u d y sit e a n d u n d er g o t h e f oll o wi n g pr oc e d ur es:  
 
 
 
 
 
 
5. 9. 2  
D a y 1 ([ Visit 2] wit hi n 2 4 h o urs of i niti al st u d y m e dic ati o n a p plic ati o n) 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
 
 
 
 
 
       
 
 
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 2 2 of 2 1 9




Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 2 3   
 
 
  
 
 
5. 9. 7  
D a y 6, 7, 8, 1 0, 1 2 , 1 4 ( Visit 7, 8, 9, 1 0, 1 1, 1 2)  
 
 
 
  
 
  
 
5. 9. 8  
D a y 2 1 ( Visit 1 3) 
 
 
 
  
 
  
 
D a y 1 4 ( Visit 1 2) will h a v e a wi n d o w of +/- 1 d a y (i. e. D a y 1 3- 1 5).  
 
D a y 2 1 ( Visit 1 3) will h a v e a wi n d o w of +/ - 2 d a ys (i. e. D a y 1 9- 2 3). 
 
5. 9. 9  
U nsc h e d ul e d Visit  
 
 
 
 
 
 
 
5. 9. 1 0  
E n d of St u d y Visit/ Visit aft er l esi o n h e ali n g wit hi n 2 4 h o urs of ti m e t o c o m pl et e 
l esi o n h e ali n g 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 2 4 of 2 1 9






Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 2 6   
 
i n v esti g at or or d esi g n e e m ust c o nt act t h e  
c o nt acts list e d i n S ecti o n 1 5 ( A p p e n dix A) at 
t h e e arli est p ossi bl e ti m e. 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
5. 1 3  
S u bj ect C o m pli a nc e 
 
S u bj ects will a p pl y t h e st u d y m e dic ati o n 5 ti m es a d a y f or 4 d a ys. S u bj ect will r ec or d  t h e 
ti m e  a n d  d at e  of  e ac h  a p plic ati o n  i n  t h e  di ar y.  T h e  s u bj ect  will  als o  r ec or d  a n y  a d v ers e 
e v e nts ex p eri e nc e d or m e dic ati o ns us e d d uri n g t h e tr e at m e nt a n d f oll o w- u p p eri o ds of t h e 
st u d y. 
 
St u d y  st aff will r e vi e w  t h e  di ar y  at  e ac h  visit  t o  e ns ur e  c o m pli a nc e  wit h  pr ot oc ol  a nd t o 
c a pt ur e  all  a d v ers e  e v e nts  a n d  us e  of  m e dic ati o n.  T h e y  will  als o  v erif y  us e  of  st u d y 
m e dic ati o n b y vis u al i ns p ecti o n of t h e t u b e.  
 
 
 
 
  All  us e d  a n d  u n us e d  t u b es of  st u d y 
m e dic ati o n will b e c oll ect e d b y t h e st u d y sit e.  
 
 
5. 1 4  
Disc o nti n u ati o n/ Wit h dr a w al of St u d y S u bj ects 
 
S u bj ects m a y  b e r e m o v e d fr o m t h e st u d y f or a n y of t h e f oll o wi n g r e as o ns: 
 T h e s u bj ect wit h dr a ws his / h er c o ns e nt f or a n y r e as o n. 
 T h e s u bj ect’s c o n diti o n h as w ors e n e d t o t h e d e gr e e t h at t h e i n v esti g at or f e els it is  
   u ns af e f or t h e s u bj ect t o c o nti n u e i n t h e st u d y. 
 T h e s u bj ect’s st u d y m e dic ati o n c o d e is u n bli n d e d. 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 A n a d v ers e e v e nt occ urs f or w hic h t h e s u bj ect d esir es t o disc o nti n u e tr e at m e nt or t h e    
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 2 7 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 2 7   
 
   i n v esti g at or d et er mi n es t h at it is i n t h e s u bj ect’s b est i nt er est t o b e disc o nti n u e d. 
 T h e s u bj ect is l ost t o f oll o w- u p.  T h e st u d y st aff will d oc u m e nt eff orts t o att e m pt t o  
           r e ac h t h e s u bj ect at l e ast t wic e b y t el e p h o n e a n d will s e n d a c ertifi e d f oll o w- u p l ett er      
           b ef or e c o nsi d eri n g t h at s u bj ect l ost t o f oll o w-u p.  All att e m pts m ust b e t h or o u g hl y    
          r ec or d e d. 
 T h e s u bj ect b ec o m es pr e g n a nt d uri n g t h e c o urs e of t h e tri al. 
 
T h e r e as o ns f or a s u bj ect b ei n g disc o nti n u e d will b e d oc u m e nt e d i n t h e s u bj ect’s r ec or ds, 
el ectr o nic c as e r e p ort f or m a n d t h e e nr oll m e nt l o g. 
 
If  a  s u bj ect  is  disc o nti n u e d  fr o m  t h e  st u d y  f or  a n y  r e as o n,  t h e  e n d  of  st u d y  pr oc e d ur es 
s h o ul d b e c o m pl et e d a n d a n y o utst a n di n g d at a a n d st u d y m e dic ati o n s h o ul d b e c oll ect e d.  
D at a,  i n  a d diti o n  t o  t h e  r e as o n  f or  disc o nti n u ati o n  a n d  t h e  d at e  of  r e m o v al,  will  b e 
r ec or d e d o n t h e E n d of St u d y C as e R e p ort F or m. 
 
I n  t h e  e v e nt  t h at  a  s u bj ect  disc o nti n u es  fr o m  t h e  st u d y  at  a n y  ti m e  d u e  t o  a n  a d v ers e 
e v e nt, t h e r e as o n f or disc o nti n u ati o n, t h e n at ur e of t h e e v e nt a n d  its cli nic al c o urs e m ust 
b e f ull y d oc u m e nt e d.  F or s uc h a s u bj ect, t h e i n v esti g at or m ust stri v e t o f oll o w t h e s u bj ect 
u ntil  t h e  a d v ers e  e v e nt  h as  r es ol v e d,  b ec o m e  cli nic all y  i nsi g nific a nt,  is  st a biliz e d,  or  t h e 
s u bj ect is l ost t o f oll o w-u p.  
 
S u bj ects,  w h o  si g nific a ntl y  w ors e n  ( e. g.,  si g nific a nt  i ncr e as e  i n  siz e  or  n u m b er  of  l esi o ns 
b e y o n d  t h e  s u bj ec t’s  us u al  p att er n,  pr o gr essi o n  of  l esi o ns  aft er  t h e  first  f e w  d a ys  of 
t h er a p y,  d e v el o p m e nt  of  s e v er e  p ai n,  or  e vi d e nc e  of  tiss u e  n ecr osis)  d uri n g t h e  t h er a p y 
s h oul d   b e  disc o nti n u e d  fr o m  t h e  st u d y  a n d  m ay  b e  pr escri b e d  st a n d ar d  t h er a p y  b y  t h e 
p h ysici a n. 
 
6.  
M A T E RI AL S A N D S U P PLI E S  
 
6. 1  St u d y M e dic ati o n 
T h e st u d y m e dic ati o n s u p pli e d b y t h e s p o ns or will c o nsist of: 
 
T est  Pr o d uct:    Ac ycl o vir  Cr e a m,  5 %-  P erri g o 
 
 
 
R ef er e n c e Pr o d uct:  Z o vir ax ® Cr e a m 5 %, V al e a nt P h ar m ac e utic als 
 
V e hicl e:    V e hicl e  of  Acycl o vir  Cr e a m,  5 %-  P erri g o 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
 
 
    
 
.  
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 2 8 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 2 8   
 
 
 
6. 2  M e dic ati o n M a n a g e m e nt  
 
6. 2. 1  
 L a b eli n g, P ac k a gi n g, Distri b uti o n, a n d R a n d o miz ati o n 
 
R a n d o miz ati o n  will  b e  p erf or m e d  acc or di n g t o  a  c o m p ut er  g e n er at e d  r a n d o miz ati o n 
sc h e m atic 
 t est: r ef er e nc e: v e hicl e.   T h e tr e at m e nt gr o u p d esi g n ati o n 
h as  b e e n  assi g n e d  t o  t h e  s u bj ect  n u m b er  o n  t h e  st u d y  m e dic ati o n  kit.    St u dy 
m e dic ati o n  is bli n d e d,  l a b el e d  a n d  p ac k a g e d, acc or di n g  t o t h e  r a n d o m  c o d e,  s o t h at 
n eit h er t h e s u bj ect n or t h e i n v esti g at or c a n i d e ntif y t h e tr e at m e nt. E ac h s u bj ect will 
b e pr o vi d e d wit h o n e of t h es e r a n d o m kits.  A n i n d e p e n d e nt t hir d p art y will h ol d t h e 
r a n d o miz ati o n c o d e t hr o u g h o ut t h e st u d y.  
 
All st u d y m e dic ati o ns will b e s u p pli e d t o t h e s u bj ects i n  
 t u b es .  E ac h s u bj ect’s 
tr e at m e nt u nit will c o nsist of o n e kit b ox c o nt ai ni n g 
 st u d y m e dic ati o n. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. 2. 2  
Pr oc e d ur e f or Br e a ki n g t h e Bli n d 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
T h e  i n v esti g at or,  st aff  at  t h e  st u d y  sit e,  st u d y  
m o nit ors,  a n d  d at a 
a n al ysis/ m a n a g e m e nt p ers o n n el ar e bli n d e d t o t h e s u bj ect assi g n m e nt. I n t h e e v e nt of 
a n  e m er g e ncy,  t h e  s p ecific  s u bj ect  tr e at m e nt  m a y  b e  i d e ntifi e d  b y  r e m o vi n g  t h e 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 2 9 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 2 9   
 
o v erl a y of t h e bli n d e d l a b el, w hic h is att ac h e d t o t h e  s t u d y m e dic ati o n l o g; h o w e v er, 
e v er y eff ort s h o ul d b e m a d e t o m ai nt ai n t h e bli n d.  T h e i n v esti g at or m ust n ot scr atc h 
off  t h e  occl u di n g  l a y er  of  t h e  l a b el  u nl ess  a bs ol ut el y  n ec ess ar y  t o  pr o vi d e  m e dic al 
tr e at m e nt  t o  a  s u bj ect  i n  a n  e m er g e nc y  sit u ati o n  o nl y  a n d  s h o ul d  s e e k  pri or 
a ut h oriz ati o n b y t h e s p o ns or or d esi g n e e w h e n p ossi bl e.  T h e  r e as o n f or br e a ki n g t h e 
bli n d  m ust  b e  cl e arl y  d oc u m e nt e d  i n  t h e  s o urc e  d o c u m e nt ati o n  a n d  C R F  a n d  t h e 
s u bj ect  m ust  b e  disc o nti n u e d  fr o m  t h e  st u dy.  T h e  s p o ns or  m ust  b e  n otifi e d 
i m m e di at el y u p o n all u n bli n di n g sit u ati o ns. 
 
  
 
6. 2. 3  
R et e nti o n S a m pl es  
 
E ac h i n v esti g ati o n al sit e w h er e st u d y m e dic ati o n is dis p e ns e d t o at l e ast o n e s u bj ect 
will  b e  r e q uir e d  b y  F e d er al  R e g ul ati o ns  t o  r a n d o ml y  s el ect  a n d  m ai nt ai n  r et e nti o n 
s a m pl es. As  p er  t h e  C o d e  of  F e d er al  R e g ul ati o ns  P art  2 1,  S ecti o n  3 2 0. 3 8( e),  “ E ac h 
r es er v e s a m pl e s h all b e st or e d u n d er c o n diti o ns c o nsist e nt wit h pr o d uct l a b eli n g a n d 
i n  a n  ar e a  s e gr e g at e d  fr o m  t h e  ar e a  w h er e  t esti n g  is  c o n d uct e d  a n d  wit h  acc ess 
li mit e d t o a ut h oriz e d p ers o n n el. E ac h r es er v e s a m pl e s h all b e r et ai n e d f or a p eri o d of 
at  l e ast  5  y e ars  f oll o wi n g  t h e  d at e  o n  w hic h  t h e  a p plic ati o n  or  s u p pl e m e nt al 
a p plic ati o n  is  a p pr o v e d,  or,  if  s uc h  a p plic ati o n  or  s u p pl e m e nt al  a p plic ati o n  is  n ot 
a p pr o v e d, at l e ast 5 y e ars f oll o wi n g t h e d at e of c o m pl eti o n of t h e bi o a v ail a bilit y st u dy 
i n  w hic h  t h e  s a m pl e  fr o m  w hic h  t h e  r es er v e  s a m pl e  w as  o bt ai n e d  w as  us e d.”  T h e 
i n v esti g at or  will  st or e  t h e  r et ai n  s a m pl e  st u d y  m e dic ati o n  u ntil  s uc h  ti m e  as 
n otific ati o n is r ec ei v e d fr o m t h e s p o ns or t h at t h e s a m pl es ar e n o l o n g er r e q uir e d. 
 
6. 2. 4  
 St or a g e a n d St u d y M e dic ati o n Acc o u nt a bilit y 
 
St u d y  m e dic ati o n  us e d  t o  c o n d uct  t his  st u d y  will  b e  m ai nt ai n e d  u n d er  a d e q u at e 
s ec urit y  b y t h e i n v esti g at or.  St u d y m e dic ati o n will b e st or e d at r o o m t e m p er at ur e at 
or b el o w 2 5° C ( 7 7° F) n ot o utsi d e t h e r a n g e of 1 5 ° C t o 3 0° C ( 5 9° t o 8 6° F) i n a s ec ur e d 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
ar e a  wit h  li mit e d  acc ess.   E ac h  i n v esti g at or  sit e will  e ns ur e t h at  t h e t e m p er at ur e of 
st u d y  m e dic ati o n  is  m o nit or e d  a n d  r ec or d e d  t hr o u g h o ut  t h e  st u d y.  T h e  st u d y 
m e dic ati o n  s h o ul d  n ot  b e  fr oz e n,  s h o ul d  b e  pr ot ect e d  fr o m  h e at  a n d  k e pt  ti g htl y 
cl os e d. T h e i n v esti g at or will n ot s u p pl y st u d y m e dic ati o n t o a n y p ers o n n ot e nr oll e d i n 
t his st u d y, or t o a n y p h ysici a n or sci e ntist exc e pt t h os e n a m e d as s u b-i n v esti g at ors.   
 
T h e cli nic p ers o n n el will k e e p a r u n ni n g i n v e nt or y of st u d y m e dic ati o n dis p e ns e d t h at             
will i ncl u d e s u bj ect n u m b ers assi g n e d a n d t h e d at e e ac h is dis p e ns e d a n d us e d. A       
st u d y m e dic ati o n acc o u nt a bilit y f or m will b e pr o vi d e d t o t h e i n v esti g at or t o  
d oc u m e nt all   m e dic ati o ns r ec ei v e d, dis p e ns e d b y a n d us e d b y e ac h s u bj ect.  At t h e  
c o ncl usi o n of t h e st u d y all u n us e d, p arti all y us e d, a n d e m pt y c o nt ai n ers m ust b e  
i n v e nt ori e d b y t h e m o nit or a n d r et ur n e d t o t h e s p o ns or, or d esi g n e e, f or d estr ucti o n. 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 0 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 3 0   
 
 
7.  
A D V E R S E R E A C TI O N S 
 
T h e p ot e nti al a d v ers e r e acti o ns of g e n eric Ac ycl o vir Cr e a m, 5 %  ar e a ntici p at e d t o b e si mil ar t o 
t h os e  o bs er v e d  i n  Z o vir ax ®  Cr e a m  5 %. A d v ers e  r e acti o ns  r el at e d  t o  tr e at m e nt  wit h  Z o vir ax ®  
Cr e a m 5 %   i ncl u d e  l oc al  a p plic ati o n  sit e  r e acti o ns  ( dr y  li ps,  d es q u a m ati o n,  dr y n ess  of  s ki n, 
cr ac k e d  li ps,  b ur ni n g  s ki n,  pr urit us,  fl a ki n ess  of  s ki n,  a n d  sti n gi n g  o n  t h e  s ki n)  as  p er  t h e 
p ac k a g e i ns ert. E ac h e v e nt occ urr e d i n l ess t h a n 1 % of s u bj ects r ec ei vi n g Z o vir ax ® Cr e a m 5 % . 
Ot h er  a d v ers e  r e acti o ns  ( a n gi o e d e m a,  a n a p h yl axis,  c o nt act  d er m atitis,  ecz e m a)  as  w ell  as 
si g ns  a n d  s y m pt o ms  of  i nfl a m m ati o n  h a v e  b e e n  r e p ort e d  wit h  Z o vir ax ®  Cr e a m  5 %  us e  i n 
cli nic al pr actic e.  
 
7. 1  D e vi ati o n fr o m t h e Pr ot oc ol f or I n di vi d u al S u bj ects 
 
W h e n a n e m er g e ncy occ urs r e q uiri n g a d e vi ati o n fr o m t h e pr ot oc ol f or a s u bj ect f or s af et y 
r e as o ns, t h e d e vi ati o n will b e o nl y f or t h at s u bj ect.  I n s uc h circ u mst a nc es, t h e i n v esti g at or 
or  ot h er  p h ysici a n  i n  att e n d a nc e  will  c o nt act  t h e  M e dic al  M o nit or  or  t h e  s p o ns or b y 
t el e p h o n e a n d f oll o w u p wit h a writt e n d escri pti o n as s o o n as p ossi bl e. I n s uc h sit u ati o ns, 
t h e o v ers e ei n g I R B s h o ul d als o b e n otifi e d. 
 
7. 2  D efi niti o ns 
 
A n  a d v ers e  e v e nt  ( A E)  is  d efi n e d  as  a n y  u nt o w ar d  m e dic al  occ urr e nc e  i n  a  s u bj ect 
a d mi nist er e d  a  m e dici n al  pr o d uct  a n d  w hic h  d o es  n ot  n ec ess aril y  h a v e  t o  h a v e  a  c a us al 
r el ati o ns hi p wit h t his tr e at m e nt. A n a d v ers e e v e nt c a n t h er ef or e b e a ny u nf a v or a bl e a n d 
u ni nt e n d e d  si g n  (f or  ex a m pl e,  a n  a b n or m al  l a b or at or y  fi n di n g),  s y m pt o m,  or  dis e as e 
t e m p or all y  ass oci at e d  wit h  t h e  us e  of  a  m e dici n al  pr o d uct,  w h et h er  or  n ot  c o nsi d er e d 
r el at e d t o t his m e dici n al pr o d uct.  
 
  A s eri o us  a d v ers e  e v e nt  ( S A E)  is  a n  a d v ers e  e v e nt  t h at  r es ults  i n  a ny  of  t h e  f oll o wi n g      
o utc o m es: 
 d e at h 
 lif e-t hr e at e ni n g e v e nt (i. e., t h e s u bj ect w as, i n t h e o pi ni o n of t h e i n v esti g at or, 
at i m m e di at e ris k of d e at h fr o m t h e e v e nt as it occ urr e d.  It d o es n ot i ncl u d e 
a n e v e nt t h at, h a d it occ urr e d i n a m or e s e v er e f or m, mi g ht h a v e c a us e d d e at h 
 r e q uir es i n-s u bj ect h os pit aliz ati o n or pr ol o n gs h os pit aliz ati o n 
 a p ersist e nt or si g nific a nt dis a bilit y/i nc a p acit y or s u bst a nti al disr u pti o n of t h e 
a bilit y t o c o n d uct n or m al lif e f u ncti o ns 
 c o n g e nit al a n o m al y/ birt h d ef ect 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
Ot h er a d v ers e e v e nts t h at m a y b e c o nsi d er e d s eri o us b as e d u p o n a p pr o pri at e 
m e dic al  j u d g m e nt,  m a y  j e o p ar diz e  t h e  s u bj ect  a n d  m a y  r e q uir e  m e dic al  or 
s ur gic al i nt er v e nti o n t o pr e v e nt o n e of t h e o utc o m es list e d a b o v e, e. g. all er gic 
br o nc h os p as m r e q uiri n g i nt e nsi v e tr e at m e nt i n a n e m er g e ncy r o o m or h o m e, 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 1 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 3 1   
 
bl o o d  d yscr asi as  or  c o nv ulsi o ns  t h at  d o  n ot  r es ult  i n  h os pit aliz ati o n,  or  t h e 
d e v el o p m e nt of dr u g d e p e n d e ncy or dr u g a b us e 
 
I m m e di at el y  R e p ort a bl e  A d v ers e  E v e nts  (I R A E):  A n y  s eri o us  A E  or  a n y  A E  t h at  n ec essit at es 
disc o nti n u ati o n of st u d y m e dic ati o n, i ncl u di n g pr e g n a ncy. 
 
U n ex p ect e d  A d v ers e  E v e nt :    A n u n ex p ect e d  ev e nt  is  a n y  a d v ers e  dr u g  ex p eri e nc e,  t h e 
s p ecificit y  or  s e v erit y  of  w hic h  is  n ot  c o nsist e nt  wit h  t h e  c urr e nt  a p pr ov e d  pr o d uct  l a b eli n g 
( p ac k a g e i ns ert) f or t h e st u d y m e dic ati o n, t h e I nv esti g at or’s Br oc h ur e, or as d escri b e d i n t h e 
cli nic al pr ot oc ol a n d c o ns e nt m at eri als.    
 
I nt e nsit y of A d v ers e E v e nts:  T h e m axi m u m i nt e nsit y of a n A E d uri n g a d ay s h o ul d b e r ec or d e d 
o n  t h e  C R F.  If  t h e  i nt e nsit y  of  a n  A E  c h a n g es  ov er  a  n u m b er  of  d a ys,  t h e n  s e p ar at e  e ntri es 
s h o ul d b e m a d e h a vi n g disti nct o ns et d at es f or t h e c h a n g es i n s e v erit y. 
 
Mil d - A Es ar e us u all y tr a nsi e nt, r e q uiri n g n o s p eci al tr e at m e nt, a n d d o n ot i nt erf er e wit h 
s u bj ect’s d ail y acti viti es. 
 
M o d er at e - A Es t y pic all y i ntr o d uc e a l o w l e v el of i nc o n v e ni e nc e or c o nc er n t o t h e s u bj ect 
a n d m a y i nt erf er e wit h d ail y acti viti es, b ut ar e us u all y a m eli or at e d b y si m pl e t h er a p e utic 
m e as ur es. 
 
S e v er e  - A Es  i nt err u pt  a  s u bj ect’s  us u al  d ail y  acti vit y  a n d  tr a diti o n all y  r e q uir e  s yst e mic 
dr u g t h er a p y or ot h er tr e at m e nt. 
 
C a us al R el ati o ns hi p t o St u d y M e dic ati o n: T h e f oll o wi n g crit eri a s h o ul d b e us e d i n ass essi n g t h e 
a p p ar e nt c a us al r el ati o ns hi p of a n A E t o st u d y m e dic ati o n.  
 
D efi nit el y - T h e A E: 
• 
f oll o ws a r e as o n a bl e t e m p or al s e q u e nc e fr o m st u d y m e dic ati o n a d mi nistr ati o n 
• 
a b at es u p o n disc o nti n u ati o n of t h e st u d y m e dic ati o n ( d ec h all e n g e) 
• 
is c o nfir m e d b y r e a p p e ar a nc e of t h e r e acti o n o n r e p e at ex p os ur e 
 
Pr o b a bl y - T h e A E: 
• 
f oll o ws a r e as o n a bl e t e m p or al s e q u e nc e fr o m st u d y m e dic ati o n a d mi nistr ati o n 
• 
a b at es u p o n disc o nti n u ati o n of t h e st u d y m e dic ati o n ( d ec h all e n g e). 
• 
c a n n ot b e r e as o n a bl y ex pl ai n e d b y t h e k n o w n c h ar act eristics of t h e s u bj ect’s st at e.  
 
P ossi bl e - T h e A E: 
• 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
f oll o ws a r e as o n a bl e t e m p or al s e q u e nc e fr o m st u d y m e dic ati o n a d mi nistr ati o n 
b ut t h at c o ul d r e a dil y b e pr o d uc e d b y a n u m b er of ot h er f act ors. 
 
U nli k el y - T h e A E : 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 2 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 3 2   
 
 f oll o ws a r e as o n a bl e t e m p or al s e q u e nc e fr o m st u d y m e dic ati o n a d mi nistr ati o n. 
 c o ul d h a v e b e e n pr o d uc e d b y eit h er t h e s u bj ect’s cli nic al st at e or b y st u dy m e dic ati o n 
a d mi nistr ati o n. 
 
N ot r el at e d - T h e A E: 
 d o es  n ot  h a v e  a  r e as o n a bl e  t e m p or al  ass oci ati o n  wit h  t h e  a d mi nistr ati o n  of  st u d y 
m e dic ati o n  
 h as s o m e ot h er o b vi o us ex pl a n ati o n f or t h e e v e nt. 
 
 
7. 3  Eliciti n g a n d R e p orti n g of A d v ers e E v e nts 
 
T h e i n v esti g at or will p eri o dic all y ass ess s u bj ects f or t h e occ urr e nc e of a dv ers e e v e nts.    
 
 
  
All a d v ers e e v e nts ( as d efi n e d i n S ecti o n 7. 2), eit h er o bs er v e d b y t h e I n v esti g at or or o n e of 
his/ h er m e dic al c oll a b or at ors, or r e p ort e d b y t h e p artici p a nt s p o nt a n e o usl y, or i n r es p o ns e 
t o  dir ect  q u esti o ni n g,  will  b e  r e p ort e d  a n d  d oc u m e nt e d  i n  t h e  s o urc e  a n d  t h e  st u d y 
r e p orti n g f or ms. W h e n r e p orti n g a n a d v ers e e v e nt, t h e I n v esti g at or m ust assi g n a s e v erit y 
gr a d e t o e ac h e v e nt a n d d ecl ar e a n o pi ni o n o n t h e r el at e d n ess/ c a us al r el ati o ns hi p of t h e 
e v e nt t o t h e st u d y m e dic ati o n or pr oc e d ur e.  S eri o us or u n ex p ect e d a d v ers e e v e nts m ust 
b e  r e p ort e d  t o  P erri g o wit hi n  2 4  h o urs   of  w h e n  t h e  I n v esti g at or  first  l e ar ns  of  t h e 
occ urr e nc e of t h e e v e nt. 
A d v ers e  e v e nts  will  b e  d oc u m e nt e d  i n  s o urc e  a n d  r ec or d e d  i n  a  ti m el y  m a n n er  o n  c as e                   
r e p ort f or ms. A d v ers e ev e nts t h at ar e i d e ntifi e d at t h e l ast ass ess m e nt visit ( or t h e e arl y 
t er mi n ati o n visit) m ust b e r ec or d e d o n t h e A E c as e r e p ort f or m ( C R F) wit h t h e st at us of t h e 
A E n ot e d.  
 
       A d v ers e e v e nts will b e r ec or d e d a n d r e p ort e d d uri n g tr e at m e nt a n d f oll o w- u p p eri o d       
       A d v ers e e v e nts s h o ul d b e f oll o w e d u ntil r es olv e d or 3 0 d a ys aft er t h e fi n al st u d y     
       tr e at m e nt.  I n a n y c as e, s eri o us a d v ers e e v e nts t h at ar e n ot r es ol v e d or c o nsi d er e d t o b e    
       c hr o nic wit hi n 3 0 d ays of t h e fi n al st u d y tr e at m e nt m ust b e f oll o w e d by t h e i n v esti g at or   
       u ntil t h e y b ec o m e r es ol v e d or ar e c o nsi d er e d t o b e c hr o nic (st a biliz e d f or at l e ast 3 0 d a ys).    
       All e v e nts t h at ar e o n g oi n g at t his ti m e will b e r ec or d e d as o n g oi n g o n t h e C R F. 
 
7. 3. 1  
Ex p e dit e d R e p orti n g R es p o nsi biliti es of t h e St u d y C e nt er 
 
F or a n y s eri o us a d v ers e e v e nt, t h e s p o ns or m ust b e n otifi e d wit hi n 2 4 h o urs
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 of w h e n  
t h e I n v esti g at or first l e ar ns of t h e occ urr e nc e of t h e e v e nt. Ex p e dit e d r e p orti n g  
r e q uir e m e nts f or s eri o us a d v ers e e v e nts ar e d escri b e d b el o w. A d e q u at e i nf or m ati o n  
m ust b e c oll ect e d wit h s u p p orti n g d oc u m e nt ati o n t o c o m pl et e a st a n d ar d r e p ort f or  
s u b missi o n t o t h e s p o ns or. T h e a d v ers e e v e nt t er m o n t h e A E c as e r e p ort f or m a n d   
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 3 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 3 3   
 
t h e  S A E  r e p ort  s h o ul d  a gr e e  ex actl y.  S p eci al  att e nti o n  s h o ul d  b e  gi v e n  t o  r ec or di n g 
h os pit aliz ati o ns a n d c o nc o mit a nt m e dic ati o ns.   
 
S u bj ects wit h u nr es ol v e d a dv ers e ev e nt(s) or s eri o us a dv ers e ev e nt(s) s h o ul d b e f oll o w e d 
by t h e i nv esti g at or u ntil t h e ev e nts ar e r es ol v e d, or t h e s u bj ect is l ost t o f oll o w- u p.  
R es ol uti o n m e a ns t h e s u bj ect h as r et ur n e d t o t h e b as eli n e st at e of h e alt h, or t h e 
i nv esti g at or d o es n ot ex p ect a ny f urt h er i m pr ov e m e nt or w ors e ni n g of t h e a d v ers e ev e nt. 
T h e i nv esti g at or s h o ul d c o nti n u e t o r e p ort a ny si g nific a nt f oll o w- u p i nf or m ati o n t o t h e 
s p o ns or u p t o t h e p oi nt t h at t h e e v e nt h as r es ol v e d.  A ny s eri o us a dv ers e ev e nt r e p ort e d 
by t h e s u bj ect t o t h e i nv esti g at or t h at occ urs wit hi n 3 0 d a ys aft er t h e l ast ass ess m e nt, a n d 
ar e d et er mi n e d b y t h e i nv esti g at or t o b e r e as o n a bl y ass oci at e d ( d efi nit e, pr o b a bl e & 
p ossi bl e) wit h t h e us e of t h e st u dy m e dic ati o n, s h o ul d b e r e p ort e d t o t h e s p o ns or wit hi n 2 4 
h o urs of w h e n t h e I nv esti g at or first l e ar ns of t h e occ urr e nc e of t h e ev e nt.   
 
W h e n  r e p orti n g  a  s eri o us  a d v ers e  e v e nt  ( S A E)  t h e  I n v esti g at or  ( or  t h e  S t u dy 
C o or di n at or) will pr o m ptl y r e p ort a n y s eri o us a d v ers e e v e nt or pr e g n a ncy t o  
 
 
m m e di at el y aft er t h e i n v esti g at or b ec o m es a w ar e 
of t h e e v e nt.  A n S A E f or m s h o ul d b e c o m pl et e d a n d s e nt b y f ax, e m ail, or o v er ni g ht 
c o uri er  
 wit hi n 2 4 h o urs of k n o wl e d g e of t h e e v e nt b y t h e sit e.  I n m a n y c as es, 
o nl y  pr eli mi n ar y  i nf or m ati o n  will  b e  a v ail a bl e.  A p pr o pri at e  f oll o w  u p  i nf or m ati o n 
s h o ul d b e s o u g ht ( h os pit al disc h ar g e s u m m ari es, o p er ati v e r e p orts etc.) a n d a f oll o w 
u p S A E r e p ort f or m s u b mitt e d.  A d esi g n ati o n of c a us alit y fr o m t h e st u dy m e dic ati o n 
s h o ul d al w a ys b e i ncl u d e d wit h a f oll o w u p r e p ort.   Ass ess a n d r e p ort t h e c a us alit y of 
t h e e v e nt. 
 
7. 3. 2  
S u b mitti n g a n Ex p e dit e d S af et y R e p ort t o t h e I R B 
 
O nc e  
r ec ei v es all s u p p orti n g d oc u m e nt ati o n f or t h e r e p ort e d e v e nt, t h e M e dic al   
M o nit or, i n c o nj u ncti o n wit h t h e s p o ns or, will d et er mi n e if t h e s af et y r e p ort is eli gi bl e  
f or ex p e dit e d r e vi e w.  
 will l o g t h e i niti al e v e nt a n d will n otif y t h e s p o ns or t h at a n  
e v e nt h as b e e n r e p ort e d wit hi n 1 b usi n ess d a y aft er i niti al r ec ei pt.  
 will c o m pl et e   
t h e r e vi e w of t h e e v e nt, e nt er i nf or m ati o n i nt o t h eir s af et y d at a b as e a n d g e n er at e  
t h e r e p ort. T his f or m, as w ell as ot h er s u p p orti n g d oc u m e nt ati o n, will b e f or w ar d e d  
t o 
 M e dic al M o nit or f or r e vi e w.  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 will fi n aliz e t h e r e p ort a n d distri b ut e it t o  
t h e s p o ns or wit hi n 2 d a ys aft er i niti al r ec ei pt. W h e n ex p e dit e d s af et y r e p orti n g t o  
r e g ul at or y a ut h oriti es is i n d e e d r e q uir e d, t h e I n v esti g at or s h o ul d r e vi e w a n d u p d at e  
a n y n e wl y a v ail a bl e m at eri als at o nc e.  F oll o w- u p q u eri es m a y b e s e nt t o t h e st u d y  
c e nt er t o f urt h er cl arif y t h e e v e nt. 
 
E ac h  ex p e dit e d  s af et y  r e p ort  will  r o uti n el y  i ncl u d e  a  bri ef  c o v er  m e m or a n d u m,  t h e 
c o m pl et e d  r e p ort,  a n d  a n y  a d diti o n al  p erti n e nt  i nf or m ati o n  r ec o m m e n d e d 
, 
t h e  s p o ns or,  or  st u d y  M e dic al  M o nit or.  O nc e  t h e  r e p ort  is  ass e m bl e d,  t h e  Pri nci p al 
I n v esti g at or  m ust  s u b mit  t h e  ex p e dit e d  s af et y  r e p ort  t o  t h e  I R B  wit hi n  t h e  r e q uir e d 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 4 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 3 4   
 
r e p orti n g ti m efr a m e. F oll o w- u p r e p orts s h o ul d b e s u b mitt e d w h e n r e q u est e d or w h e n 
p erti n e nt i nf or m ati o n b ec o m es a v ail a bl e.  
 
W h e n a Pri nci p al I n v esti g at or r ec ei v es a n ex p e dit e d s af et y r e p ort fr o m  
or t h e   
 
s p o ns or d et aili n g a d v ers e e v e nts occ urri n g at ot h er st u d y c e nt ers u n d er t his pr ot oc ol,    
it  m ust  b e  pr o m ptl y  s u b mitt e d  t o  t h e  st u d y  c e nt er’s  I R B.    T h e  Pri nci p al  I n v esti g at or   
m ust  r et ai n  a  c o p y  of  s uc h  r e p orts  as  s u b mitt e d  t o  t h eir  I R B 
i n  t h e  sit e’s  st u d y    
R e g ul at or y Bi n d er.   
 
7. 4  S A E  & A Es R e q uiri n g Disc o nti n u ati o n of St u d y M e dic ati o n, i ncl u di n g Pr e g n a nci es 
 
A N Y  S A E,  W HI C H  O C C U R S  A F T E R  A  S U BJ E C T  H A S  I NI TI A T E D  T H E  S T U D Y  M E DI C A TI O N , 
W H E T H E R  O R  N O T  R EL A T E D  T O  S T U D Y  M E DI C A TI O N,  M U S T  B E  R E P O R T E D  T O  
 
I M M E DI A T EL Y ( WI T HI N 2 4 H O U R S) VI A T EL E P H O N E O R F A C SI MIL E. I F I NI TI ALL Y R E P O R T E D 
VI A  T EL E P H O N E,  T HI S  M U S T  B E  F OLL O W E D- U P  B Y  A  F A C SI MIL E  O F  T H E  W RI T T E N  S A E 
R E P O R T WI T HI N 2 4 H O U R S O F T H E C ALL T O  
. 
 
N o n -s eri o us e v e nts t h at r e q uir e disc o nti n u ati o n of st u d y m e dic ati o n (i ncl u di n g l a b or at or y 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
a b n or m aliti es) s h o ul d b e r e p ort e d t o t h e s p o ns or i m m e di at el y a n d wit hi n 3 w or ki n g d a ys. 
S u bj ects w h o disc o nti n u e d u e t o ex p eri e nci n g a dv ers e e v e nts s h o ul d b e f oll o w e d cli nic all y 
u ntil t h eir h e alt h h as r et ur n e d t o b as eli n e st at us, or u ntil all p ar a m et ers h a v e r et ur n e d t o 
n or m al.  It is ex p ect e d t h at t h e i n v esti g at or will pr o vi d e or arr a n g e a p pr o pri at e s u p p orti v e 
c ar e f or t h e s u bj ect. 
 
A  s u bj ect  w h o  ex p eri e nc es  a  s e v er e  a d v ers e  ev e nt  r el at e d  t o  st u d y  m e dic ati o n  will  b e 
disc o nti n u e d fr o m t h e st u d y. 
 
T h e n otific ati o n a b o ut a n y s eri o us a d v ers e e v e nt s h o ul d b e dir ect e d t o: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 5 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 3 5   
 
 
7. 4. 1  
Pr e g n a ncy 
 
At t h e ti m e a Pri nci p al I nv esti g at or or sit e p ers o n n el b ec o m es a w ar e t h at a st u d y   
 
               p artici p a nt b ec a m e pr e g n a nt f oll o wi n g st u d y p artici p ati o n, t h e Pri nci p al I n v esti g at or 
     or d esi g n e e will r e p ort t h e pr e g n a ncy i m m e di at el y b y p h o n e a n d b y f axi n g a     
     c o m pl et e d Pr e g n a ncy R e p ort t o  
wit hi n o n e w or ki n g d a y of b ei n g n otifi e d of t h e      
     pr e g n a ncy r e p ort. 
 
   T h e r e p ort will i ncl u d e t h e f oll o wi n g el e m e nts: 
 P artici p a nt ( m ot h er’s) c o d e d st u d y i d e ntifi er;  
 D at e of p artici p a nt’s l ast m e nstr u al p eri o d;  
 T ot al acc u m ul at e d d os e of st u d y tr e at m e nt a d mi nist er e d t o d at e; 
 D at e of st u d y m e dic ati o n a d mi nistr ati o n. 
 
 
   T h e i n v esti g at or will f oll o w t h e s u bj ect u ntil c o m pl eti o n of t h e pr e g n a ncy a n d m ust     
               ass ess t h e o utc o m e i n t h e s h ort est p ossi bl e ti m e b ut n ot m or e t h a n 3 0 d a ys wit hi n  
    
               c o m pl eti o n of t h e pr e g n a ncy. 
 
U p o n d eli v er y, misc arri a g e or a b orti o n, t h e Pri nci p al I n v esti g at or or d esi g n e e m ust  
                            
f or w ar d a f oll o w- u p Pr e g n a ncy R e p ort wit h a n y r el e v a nt i nf or m ati o n o n t h e pr es e nt  
c o n diti o n of t h e f et us t o t h e  
 i ncl u di n g: 
 M ot h er ’s c o d e d st u d y i d e ntifi er(s); 
 G est ati o n al a g e at d eli v er y, misc arri a g e or a b orti o n; 
 Birt h w ei g ht, g e n d er, l e n gt h a n d h e a d circ u mf er e nc e, if a v ail a bl e; 
 A p g ar sc or es r ec or d e d aft er birt h, if a v ail a bl e; 
 A n y a b n or m aliti es. 
 
    If t h e o utc o m e of t h e pr e g n a ncy m e ets t h e crit eri a f or i m m e di at e cl assific ati o n of a n        
    S A E  ( e. g., s p o nt a n e o us or t h er a p e utic a b orti o n [ a n y c o n g e nit al a n o m al y d et ect e d i n a n  
    a b ort e d f et us is t o b e d oc u m e nt e d], still birt h, n e o n at al d e at h, or c o n g e nit al a n o m al y),  
    t h e i n v esti g at or will r e p ort t h e e v e nt b y p h o n e a n d b y f axi n g a c o m pl et e d S A E r e p ort  
    f or m t o  
wit hi n o n e w or ki n g d a y of b ei n g n otifi e d of t h e pr e g n a ncy r e p ort. 
 
    If  
r es p o nsi biliti es f or t h e tri al ar e c o m pl et e d b ef or e t h e o utc o m e of t h e  
    pr e g n a ncy is k n o w n, t h e s p o ns or will  ass u m e t h e r es p o nsi bilit y f or f oll o wi n g u p o n t h e     
    pr e g n a ncy. 
 
7. 5  P ost St u d y A d v ers e E v e nts 
 
7. 5. 1  
N o n -s eri o us A d v ers e E v e nts 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 6 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 3 6   
 
A d v ers e e v e nts t h at ar e i d e ntifi e d at t h e l ast ass ess m e nt visit ( or t h e e arl y t er mi n ati o n 
visit)  m ust  b e  r ec or d e d  o n  t h e  A E  c as e  r e p ort  f or m  ( C R F)  wit h  t h e  st at us  of  t h e  A E 
n ot e d.   
 
7. 5. 2  
S eri o us A d v ers e E v e nts 
 
S eri o us  a d v ers e  e v e nts  t h at  ar e  i d e ntifi e d  o n  t h e  l ast  ass ess m e nt  visit  ( or  t h e  e arl y 
t er mi n ati o n  visit)  m ust  b e  r ec or d e d  o n  t h e  A E  c as e  r e p ort  f or m  ( C R F)  p a g e  a n d 
r e p ort e d t o t h e  s p o ns or  acc or di n g  t o  t h e  pr oc e d ur es  o utli n e d  a b o v e.  S u bj ects  wit h 
u nr es ol v e d  pr e vi o usl y  r e p ort e d  s eri o us  a d v ers e  e v e nts,  or  a n y  n e w  s eri o us  a d v ers e 
e v e nts i d e ntifi e d o n t h e l ast ass ess m e nt visit, s h o ul d b e f oll o w e d b y t h e i n v esti g at or 
u ntil t h e e v e nts ar e r es olv e d, or t h e s u bj ect is l ost t o f oll o w- u p.  R es ol uti o n m e a ns t h e 
s u bj ect  h as  r et ur n e d  t o  t h e  b as eli n e  st at e  of  h e alt h,  or  t h e  i n v esti g at or  d o es  n ot 
ex p ect a n y f urt h er i m pr o v e m e nt or w ors e ni n g of t h e a d v ers e e v e nt.  T h e i n v esti g at or 
s h o ul d c o nti n u e t o r e p ort a n y si g nific a nt f oll o w- u p i nf or m ati o n t o t h e s p o ns or u p t o 
t h e  p oi nt  t h at  t h e  e v e nt  h as  r es ol v e d.  A n y  s eri o us  a d v ers e  e v e nt  r e p ort e d  b y  t h e 
s u bj ect t o t h e i n v esti g at or t h at occ urs aft er t h e l ast ass ess m e nt, a n d ar e d et er mi n e d 
b y t h e i n v esti g at or t o b e r e as o n a bl y ass oci at e d wit h t h e us e of t h e st u dy m e dic ati o n , 
s h o ul d b e r e p ort e d t o P erri g o P h ar m ac e utic als. 
 
8.  
S T A TI S TI C AL C O N SI D E R A TI O N S 
 
8. 1  G e n er al C o nsi d er ati o ns  
 
St atistic al  a n al ys es  will  b e  c o n d uct e d  b y  t h e  S p o ns or ’s  d esi g n e e.  T h e  mI T T  a n d  P P 
p o p ul ati o ns will b e us e d i n t h e a n al ysis of effic acy e n d p oi nts a n d t h e s af et y p o p ul ati o n f or 
s af et y e n d p oi nts. S u bj ects will b e a n al yz e d as tr e at e d. S u m m ar y dis pl a ys will b e pr es e nt e d 
b y tr e at m e nt gr o u p.  
 
Hy p ot h es es will b e t est e d at t h e 5 % st atistic al si g nific a nc e l e v el, u nl ess ot h er wis e s p ecifi e d. 
N o i nt eri m a n al ysis is pl a n n e d. Effic acy a n d s af et y a n al ys es will b e p erf or m e d usi n g S A S ® 
v ersi o n 9. 2 or l at er ( S A S I nstit ut e, C ar y, N C), or c o m p ar a bl e s oft w ar e. 
 
All c e ns or e d d at a will b e acc o u nt e d f or usi n g a p pr o pri at e st atistic al m et h o ds. S e e S ecti o n 
8. 4. 1 f or d et ails. 
 
All  d at a  c oll ect e d  o n  t h e  e C R F  will  b e  list e d.  R o uti n e  d at a  listi n g  or  t a b ul ati o n  r e vi e w  of 
bli n d e d  d at a  d uri n g  t h e  st u d y  c o n d uct  will  b e  p erf or m e d  t o  i d e ntif y  missi n g  d at a, 
a n o m ali es,  o utli ers,  etc.  A  c o m pl et e  d escri pti o n  of  d at a  h a n dli n g  r ul es  a n d  pl a n n e d 
st atistic al  a n al ys es  will  b e  d escri b e d  i n  a  s e p ar at e  st atistic al  a n al ysis  pl a n  ( S A P)  pri or  t o 
d at a l oc k a n d u n bli n di n g pr oc e d ur es ar e c o m pl et e d at t h e e n d of t h e st u d y. 
 
8. 2  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
A n al ysis P o p ul ati o ns  
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 7 of 2 1 9




Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 3 8   
 
 
 
 
 
 
 
  
 
8. 4  M e as ur es a n d A n al ysis  
 
8. 4. 1  
Effic ac y E n d p oi nt a n d A n al ysis 
 
T h e pri m ar y effic acy e n d p oi nt will b e t h e ti m e t o c o m pl et e h e ali n g of l esi o ns ( d efi n e d 
as  l oss of cr ust a n d r e- e pit h eli aliz ati o n wit h or wit h o ut er yt h e m a, as ass ess e d b y t h e 
i n v esti g at or,  b as e d  o n  b ot h  cli nic al  o bs er v ati o n  a n d  r e vi e w  of  t h e  s u bj ect  di ar y), 
m e as ur e d i n d a ys/ h o urs fr o m t h e ti m e of first d osi n g.  
  
 
 
 
 
 
  
 
 
 
.  
 
 
     E q ui v al e nc e of Cli nic al E n d p oi nt A n al ysis 
 
 
T h e m e a n ti m e t o c o m pl et e h e ali n g of t h e l esi o n f or t h e t est a n d r ef er e nc e tr e at m e nts 
will  b e  esti m at e d  usi n g  a n al ysis  of  V ari a nc e  ( A N O V A)  wit h  tr e at m e nt  a n d  c e nt er as 
fix e d eff ects i n t h e m o d el. T h e 9 0 % c o nfi d e nc e i nt er v al f or t h e r ati o ( T est/ R ef er e nc e) 
of m e a n ti m e- t o-c o m pl et e h e ali n g will b e o bt ai n e d b y Fi ell er’s m et h o d.  A pl ot f or t h e 
r ati o  ( T est/ R ef er e nc e)  of  m e a n  ti m e-t o-c o m pl et e  h e ali n g  a n d  ass oci at e d  9 0 %  CI  will 
b e  pr es e nt e d.  F or  t h e  ti m e  t o  c o m pl et e  h e ali n g  of  l esi o n  t h e  T est  tr e at m e nt  will  b e 
c o nsi d er e d  t o  b e  t h er a p e utic all y  e q ui v al e nt  t o  t h e  R ef er e nc e  tr e at m e nt  if  t h e 
c alc ul at e d  9 0 %  c o nfi d e nc e  i nt er v al  of  t h e  r ati o  of  t h e  m e a ns  ( T est/ R ef er e nc e)  f alls 
wit hi n  t h e  i nt er v al  of  0. 8 0  t o  1. 2 5.  T h er a p e utic  e q ui v al e nt  e v al u ati o ns  i n  t h e  p er-
pr ot oc ol ( P P) p o p ul ati o n will b e c o nsi d er e d t h e d efi niti v e a n al ysis. T his a n al ysis will b e 
r e p e at e d i n t h e mI T T p o p ul ati o n a n d will b e c o nsi d er e d t h e s u p p orti v e a n al ysis. R ef er 
t o t h e st atistic al a n al ysis pl a n f or a n al ysis d et ails. 
 
 
  
         A n al ysis of S u p eri orit y b et w e e n acti v e f or m ul ati o n a n d v e hicl e 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 9 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 3 9   
 
 
  F or t h e ti m e t o c o m pl et e h e ali n g of t h e l esi o n, s u bj ects w h o r ec ei v e d activ e     
 tr e at m e nt will b e c o m p ar e d t o t h os e w h o r ec eiv e d t h e V e hicl e as tr e at m e nt i n   
 or d er t o d et er mi n e if s u p eri or effic ac y h as b e e n att ai n e d. 
 
T h e ti m e- t o-c o m pl et e h e ali n g of b ot h t h e activ e pr o d ucts a n d V e hicl e will b e a n alyz e d 
usi n g A n al ysis of V ari a nc e ( A N O V A) e v al u ati o ns wit h tr e at m e nt a n d c e nt er as fix e d eff ects 
i n t h e m o d el.   
 
E ac h activ e tr e at m e nt gr o u p will b e c o m p ar e d t o t h e V e hicl e gr o u p usi n g a -t w o-si d e d t est 
a n d t est e d at a n al p h a l ev el of 0. 0 5. T h e m e a n a n d its 9 5 % c o nfi d e nc e i nt erv al will b e 
r e p ort e d. 
 
S u p eri orit y will b e c o nsi d er e d d e m o nstr at e d if t h e m e a ns f or b ot h acti v e tr e at m e nts ar e 
st atistic ally diff er e nt fr o m ( p < 0. 0 5), a n d s m all er t h a n, t h at f or t h e V e hicl e 
 
T h e a n al ysis of s u p eri ority usi n g t h e mI T T p o p ul ati o n will b e c o nsi d er e d t h e   
d efi niti v e a n al ysis. T his a n al ysis will b e r e p e at e d usi n g P P p o p ul ati o n a n d will b e  
c o nsi d ere d as s u p p orti v e a n al ysis. R ef er t o t h e st atistic al a n al ysis pl a n f or a n al ysis 
d et ails. 
 
 
8. 4. 2  
S af et y E n d p oi nts a n d A n al ysis 
 
 
     T h e s af et y p o p ul ati o n will b e us e d i n t h e s af et y a n al ys es.  
 
                All A Es will b e cl assifi e d wit h r es p ect t o syst e m or g a n cl ass ( S O C) a n d pr ef err e d t er m     
                usi n g M e d D R A. A tr e at m e nt- e m er g e nt A E is a n e v e nt t h at occ urs or w ors e ns aft er t h e                     
                a d mi nistr ati o n of first d os e of st u d y m e dic ati o n.  T h e A E pr ofil e will b e c h ar act eriz e d   
                wit h s e v erit y a n d attri b uti o n ( u nr el at e d a n d r el at e d) t o st u d y m e dic ati o n. R el at e d A Es   
                will b e e v e nts t h at ar e d efi nit el y, p ossi bl y or pr o b a bl y r el at e d t o tr e at m e nt i n t h e    
                i n v esti g at or’s j u d g m e nt. 
 
      T h e n u m b er a n d p erc e nt of p ati e nts w h o r e p ort tr e at m e nt- e m er g e nt A Es will b e     
      s u m m ariz e d f or e ac h tr e at m e nt gr o u p. A d diti o n al s u m m ari es b y s e v erity a n d     
      r el ati o ns hi p t o st u d y m e dic ati o n will b e pr es e nt e d f or e ac h tr e at m e nt gr o u p. I n    
      a d diti o n, t h e n u m b er a n d p erc e nt of p ati e nts w h o r e p ort e d tr e at m e nt- e m er g e nt A Es  
      of i nt er est a n d s eri o us A Es will b e s u m m ariz e d f or e ac h tr e at m e nt gr o u p.  
 
8. 5  C h ar act eristics of S u bj ects at Scr e e ni n g 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
D e m o gr a p hic  a n d  b as eli n e  c h ar act eristics  will  b e  s u m m ariz e d  usi n g  I nt e nt- t o- Tr e at  (I T T) 
P o p ul ati o n b y tr e at m e nt gr o u ps. 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 0 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4 0   
 
A g e (y e ars), h ei g ht at scr e e ni n g (c m), b o d y w ei g ht at scr e e ni n g ( k g), a n d b o d y m ass i n d ex 
( B MI)  at  scr e e ni n g  i n  k g/ m 2  will  b e  s u m m ariz e d  usi n g  d escri pti v e  st atistics  a n d  g e n d er, 
r ac e, a n d et h nicit y will b e s u m m ariz e d usi n g fr e q u e nci es a n d p erc e nt a g es. 
 
9.  
C O N S E N T/ A S S E N T C O N SI D E R A TI O N S A N D P R O C E D U R E S 
 
It  will  b e  m a d e  cl e ar  t o  t h e  s u bj ect  t h at,  f or  t h e  p ur p os es  of  t h e  st u d y, t h e y  ar e  c o ns e nti n g 
o nl y f or t o pic al a p plic ati o n of m e dic ati o n or v e hicl e.  I n v esti g at ors m a y disc uss t h e a v ail a bilit y 
of  t h e  st u d y  a n d  t h e  p ossi bilit y  f or  e ntr y  wit h  a  p ot e nti al  s u bj ect  wit h o ut  first  o bt ai ni n g 
c o ns e nt/ ass e nt. H o w e v er, i nf or m e d c o ns e nt/ ass e nt m ust b e o bt ai n e d a n d d oc u m e nt e d pri or 
t o  i niti ati o n  of  a n y  pr oc e d ur es  t h at  ar e  p erf or m e d  s ol el y  f or  t h e  p ur p os e  of  d et er mi ni n g 
eli gi bilit y f or r es e arc h, i ncl u di n g wit h dr a w al fr o m c urr e nt m e dic ati o n(s).  W h e n t his is d o n e i n 
a ntici p ati o n of, or i n pr e p ar ati o n f or, t h e r es e arc h, it is c o nsi d er e d t o b e p art of t h e r es e arc h. 
 
T h e st u d y m ust b e a p pr ov e d i n writi n g b y a n a p pr o pri at e I R B as d efi n e d b y F D A r e g ul ati o ns.  A 
c o p y of t h e L ett er of A p pr o v al fr o m t h e I R B, w hic h als o c o nt ai ns s p ecific i d e ntific ati o n of t h e 
d oc u m e nts a p pr o v e d, m ust b e r ec ei v e d b y t h e s p o ns or, pri or t o st u d y c o m m e nc e m e nt. 
 
P eri o dic st at us r e p orts m ust b e s u b mitt e d t o t h e I R B at l e ast a n n u all y as r e q uir e d b y t h e sit e’s 
I R B, as w ell as n otific ati o n of c o m pl eti o n of t h e st u d y a n d a fi n al r e p ort wit hi n t hr e e m o nt hs of 
st u d y c o m pl eti o n or t er mi n ati o n.  A c o p y of all r e p orts s u b mitt e d t o t h e I R B m ust b e s e nt t o 
t h e s p o ns or. 
 
T h e i n v esti g at or(s) h as b ot h et hic al a n d l e g al r es p o nsi bilit y t o e ns ur e t h at e ac h s u bj ect b ei n g 
c o nsi d er e d f or i ncl usi o n i n t his st u d y is gi v e n a f ull ex pl a n ati o n of t h e pr ot oc ol.  T his s h all b e 
d oc u m e nt e d o n a writt e n i nf or m e d c o ns e nt/ ass e nt f or m, w hic h s h all b e a p pr o v e d b y t h e s a m e 
I R B r es p o nsi bl e f or a p pr o v al of t his pr ot oc ol. E ac h i nf or m e d c o ns e nt/ ass e nt f or m s h all i ncl u d e 
t h e el e m e nts r e q uir e d by F D A r e g ul ati o ns i n 2 1 C F R P art 5 0.  T h e i n v esti g at or a gr e es t o o bt ai n 
a p pr o v al  fr o m  t h e  s p o ns or  of  a n y  writt e n  i nf or m e d  c o ns e nt/ ass e nt  f or m  us e d  i n  t h e  st u d y, 
pr ef er a bl y pri or t o s u b missi o n t o t h e I R B. 
 
O nc e  t h e  a p pr o pri at e  ess e nti al  i nf or m ati o n  h as  b e e n  pr o vi d e d  t o  t h e  s u bj ect  a n d  f ull y 
ex pl ai n e d  b y  t h e  i n v esti g at ors  ( or  a  q u alifi e d  d esi g n e e)  a n d  it  is  f elt  t h at  t h e  s u bj ect 
u n d erst a n ds  t h e  i m plic ati o ns  of  p artici p ati n g,  t h e  I R B- a p pr o v e d  writt e n  i nf or m e d 
c o ns e nt/ ass e nt  f or m  s h all  b e  si g n e d  b y  t h e  s u bj ect a n d/ or  t h eir  p ar e nt/l e g all y  a ut h oriz e d 
r e pr es e nt ati v e  a n d  t h e  p ers o n  o bt ai ni n g  c o ns e nt/ ass e nt  (i n v esti g at or  or  d esi g n e e).    T h e 
s u bj ect s h all b e gi v e n a c o p y of t h e si g n e d i nf or m e d c o ns e nt/ ass e nt f or m a n d t h e i n v esti g at or 
s h all k e e p t h e ori gi n al o n fil e. 
 
If t h e s u bj ect f ails t o m e et t h e i ncl usi o n/ excl usi o n crit eri a at t h e c o ncl usi o n of t h e scr e e ni n g 
p h as e,  t h e  s u bj ect  will  b e  wit h dr a w n  fr o m  scr e e ni n g.    I n  t h e  e v e nt  t h at  t h e  s u bj ect  is  r e-
scr e e n e d f or st u d y p artici p ati o n, a n e w i nf or m e d c o ns e nt/ ass e nt f or m m ust b e si g n e d.  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 1 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4 1   
 
 
9. 1  S u bj ect C o nfi d e nti alit y 
 
All p artici p a nts ar e c o nc er n e d f or t h e i n di vi d u al s u bj ect’s pri v acy a n d, t h er ef or e, all s u bj ect 
d at a will b e i d e ntifi e d o nl y b y a s u bj ect i d e ntific ati o n n u m b er a n d s u bj ect i niti als. H o w e v er, 
i n  c o m pli a nc e  wit h  f e d er al  g ui d eli n es  r e g ar di n g  t h e  m o nit ori n g  of  cli nic al  st u di es  a n d  i n 
f ulfill m e nt of his/ h er o bli g ati o ns t o t h e s p o ns or, it is r e q uir e d t h at t h e i nv esti g at or p er mit 
t h e  st u d y  m o nit or,  a n y  S p o ns or  a ut h oriz e d  r e pr es e nt ati v e,  a n d/ or  F D A  r e pr es e nt ati v e  t o 
r e vi e w  t h at  p orti o n  of  t h e  s u bj ect’s m e dic al  r ec or d  t h at  is  dir ectl y  r el at e d  t o  t h e  st u d y.  
T his  s h all  i ncl u d e  all  st u d y  r el e v a nt  d oc u m e nt ati o n  i ncl u di n g  s u bj ect  m e dic al  hist ori es  t o 
v erif y  eli gi bilit y,  l a b or at or y  t est  r es ult  r e p orts  t o  v erif y  tr a nscri pti o n  acc ur ac y, 
a d missi o n/ disc h ar g e s u m m ari es f or h os pit al st ays occ urri n g w hil e t h e s u bj ect is e nr oll e d i n 
t h e st u d y a n d a ut o ps y r e p orts f or d e at hs occ urri n g d uri n g t h e st u d y. 
 
As  p art  of  t h e  r e q uir e d  c o nt e nt  of  i nf or m e d  c o ns e nt,  t h e  s u bj ect  m ust  b e  i nf or m e d  t h at 
his/ h er m e dic al c h art m a y b e r e vi e w e d b y t h e s p o ns or or t h eir a ut h oriz e d r e pr es e nt ati v e, 
or  a  r e pr es e nt ati v e  of  t h e  F D A.    S h o ul d  acc ess  t o  t h e  m e dic al  r ec or d  r e q uir e  a  s e p ar at e 
w ai v er  or  a ut h oriz ati o n,  it  is  t h e  i n v esti g at or’s  r es p o nsi bilit y  t o  o bt ai n  s uc h  p er missi o n 
fr o m t h e s u bj ect i n writi n g b ef or e t h e s u bj ect is e nt er e d i nt o t h e st u d y. 
 
T o  pr es er v e  t h e  s u bj ect's  c o nfi d e nti alit y,  t h e  d at a  c oll ect e d  will  b e  a v ail a bl e  o nl y  t o  t h e 
i n v esti g at ors  of  t h e  st u d y,  t h eir  s u p p ort  st aff,  t h e  s p o ns or  or  t h eir  a ut h oriz e d 
r e pr es e nt ati v e a n d p ossi bl y t h e F D A. 
 
All  r e p orts  a n d  c o m m u nic ati o ns  r el ati n g  t o  t h e  s u bj ect  i n  t h e  st u d y  will  i d e ntif y  e ac h 
s u bj ect o nl y b y t h e s u bj ect’s i nitials a n d b y t h e s u bj ect n u m b er. T h e i n v esti g at or a gr e es t o 
f ur nis h  t h e  s p o ns or wit h   c o m pl et e  s u bj ect  i d e ntific ati o n,  if  n ec ess ar y  o n  a  c o nfi d e nti al 
f oll o w- u p  f or m,  w hic h  will  b e  us e d  f or  t h e  p ur p os e  of  a  l o n g-t er m  f oll o w- u p,  if  n e e d e d.  
T his will b e tr e at e d wit h strict a d h er e nc e t o pr of essi o n al st a n d ar ds of c o nfi d e nti alit y a n d 
will b e fil e d at t h e s p o ns or u n d er a d e q u at e s ec urit y a n d r estrict e d acc essi bilit y. 
 
1 0.  
C O N D U C T O F S T U D Y 
 
T h e i n v esti g ati o n al sit e is t o m ai nt ai n c o m pl et e d oc u m e nt ati o n of all e v e nts a n d t h e ti m es at 
w hic h t h e y occ ur. 
 
 
 
 
1 0. 1  
C o m pl eti o n of St u d y 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
T h e i n v esti g ati o n al sit e will c o m pl et e t h e st u d y a n d c o m pl et e all d oc u m e nt ati o n r e q uir e d 
i n s atisf act or y c o m pli a nc e wit h t h e pr ot oc ol. It is a gr e e d t h at, f or r e as o n a bl e c a us e, eit h er 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 2 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4 2   
 
t h e  i n v esti g at or  or  t h e  s p o ns or m a y   t er mi n at e  t his  st u d y  b ef or e  c o m pl eti o n  pr o vi d e d 
writt e n n otic e is s u b mitt e d at a r e as o n a bl e ti m e i n a d v a nc e of i nt e n d e d t er mi n ati o n.  A n y 
ext e nsi o n of t his st u d y m ust b e m ut u all y a gr e e d u p o n i n writi n g b y b ot h t h e i n v esti g at or 
a n d t h e s p o ns or. 
 
 
1 0. 2  
Pr ot oc ol A m e n d m e nts 
 
T h e I n v esti g at or will n ot m a k e a n y c h a n g es t o t his pr ot oc ol wit h o ut pri or writt e n c o ns e nt 
fr o m  t h e  s p o ns or  a n d  s u bs e q u e nt  a p pr o v al  b y  t h e  I R B.    A n y  p er m a n e nt  c h a n g e  t o  t h e 
pr ot oc ol, w h et h er it is a n o v er all c h a n g e or a c h a n g e f or s p ecific st u d y c e nt er(s), m ust b e 
h a n dl e d as a pr ot oc ol a m e n d m e nt. A n y a m e n d m e nt t o t h e pr ot oc ol t h at a p p e ars i n dic at e d 
as t h e st u d y pr o gr ess es will b e f ull y disc uss e d b et w e e n 
 a n d  
P erri g o.  If  a gr e e m e nt  is r e ac h e d r e g ar di n g  t h e n e e d  f or  a n  a m e n d m e nt,  t h e  a m e n d m e nt 
will  b e  writt e n  b y  t h e  s p o ns or.  T h e  writt e n  a m e n d m e nt  m ust  b e  s u b mitt e d  t o  t h e 
c h air m a n  of  t h e  I R B  i d e ntifi e d  wit h  t his  r es p o nsi bilit y.  Exc e pt  f or  ‘ a d mi nistr ati v e 
a m e n d m e nts’,  i n v esti g at ors  m ust   a w ait  I R B  a p pr o v al  of  pr ot oc ol  a m e n d m e nts  b ef or e 
i m pl e m e nti n g t h e c h a n g e(s). A d mi nistr ati v e a m e n d m e nts ar e d efi n e d t o h a v e n o eff ect o n 
t h e  s af et y  of  t h e  r es e arc h  s u bj ects,  sc o p e  of  t h e  i n v esti g ati o n,  or  q u alit y  of  t h e  tri al.  
H o w e v er,  a  pr ot oc ol  c h a n g e  i nt e n d e d  t o  eli mi n at e  a n  a p p ar e nt  i m m e di at e  h az ar d  t o 
s u bj ects s h o ul d b e i m pl e m e nt e d i m m e di at el y, a n d t h e I R B n otifi e d wit hi n fi v e d a ys.   T h e 
s p o ns or will s u b mit pr ot oc ol a m e n d m e nts t o t h e F D A or ot h er r e g ul at or y a g e nci es. 
 
W h e n,  i n  t h e  j u d g m e nt  of  t h e  r e vi e wi n g  I R B,  t h e  i n v esti g at ors  a n d/ or  t h e  s p o ns or,  t h e 
a m e n d m e nt  t o  t h e  pr ot oc ol  s u bst a nti all y  alt ers  t h e  st u d y  d esi g n  a n d/ or  i ncr e as es  t h e 
p ot e nti al  ris k  t o  t h e  s u bj ect,  t h e  c urr e ntl y  a p pr o v e d  writt e n  i nf or m e d  c o ns e nt  f or m  will 
r e q uir e si mil ar m o dific ati o n.  I n s uc h c as es, r e p e at i nf or m e d c o ns e nt will b e o bt ai n e d fr o m 
s u bj ects e nr oll e d i n t h e st u d y b ef or e ex p ecti n g c o nti n u e d p artici p ati o n. 
 
1 1.  
R E C O R D S M A N A G E M E N T 
 
1 1. 1  
D at a C oll ecti o n 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
All  d at a  c oll ect e d  i n  t his  st u d y  will  b e  e nt er e d i nt o  eC R Fs,  v erifi e d  b y  m o nit ori n g,  a n d 
s u b mitt e d f or st atistic al e v al u ati o n as d escri b e d b el o w.  E dit c h ec ks will b e r u n o n t h e d at a 
a n d q u eri es iss u e d as n e e d e d. O nc e all d at a is cl e a n e d, f ull q u alit y c o ntr ol v erific ati o n will 
b e d o n e pri or t o br e a ki n g t h e bli n d. Aft er all d at a ar e c orr ectl y e nt er e d, t h e d at a b as e will 
b e  l oc k e d  a n d  s u b mitt e d  f or  a p pr o pri at e  Q u alit y  Ass ur a nc e  v erific ati o ns  b ef or e  t h e 
tr e at m e nt assi g n m e nt c o d e is br o k e n.  All d at a c oll ect e d i n t h e C R Fs will b e d oc u m e nt e d i n 
s u bj ect d at a listi n gs a n d s u m m ariz e d i n t a bl es, as a p pr o pri at e. 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 3 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4 3   
 
D uri n g  e ac h  s u bj ect’s  visit  t o  t h e  cli nic,  a d esi g n e e  p artici p ati n g  i n  t h e  st u d y  will  r ec or d 
pr o gr ess  n ot es t o  d oc u m e nt  all  si g nific a nt  o bs er v ati o ns.    At  a  mi ni m u m,  t h es e n ot es  will 
c o nt ai n: 
 
a)  D oc u m e nt ati o n of t h e i nf or m e d c o ns e nt pr oc ess; 
b)  T h e d at e of t h e visit a n d t h e c orr es p o n di n g Visit i n t h e st u d y sc h e d ul e; 
c) G e n er al s u bj ect st at us r e m ar ks, i ncl u di n g a n y si g nific a nt m e dic al fi n di n gs.  T h e s e v erit y, 
fr e q u e ncy,  a n d  d ur ati o n  of  a n y  a d v ers e  e v e nts  a n d  t h e  i n v esti g at or's  ass ess m e nt  of 
r el ati o ns hi p t o st u d y m e dic ati o n m ust als o b e r ec or d e d. 
d)  A n y c h a n g es i n c o nc o mit a nt m e dic ati o ns or d os a g es; 
e)  A g e n er al r ef er e nc e t o t h e pr oc e d ur es c o m pl et e d; a n d 
f) T h e si g n at ur e ( or i niti als) a n d d at e of all cli nici a ns w h o m a d e a n e ntr y i n t h e pr o gr ess 
n ot es. 
 
I n  a d diti o n,  a n y  c o nt act  wit h  t h e  s u bj ect  vi a  t el e p h o n e  or  ot h er  m e a ns  t h at  pr o vi d es 
si g nific a nt cli nic al i nf or m ati o n will als o b e d oc u m e nt e d i n t h e pr o gr ess n ot es as d escri b e d 
a b o v e. 
 
A n y c h a n g es t o i nf or m ati o n i n t h e st u d y pr o gr ess n ot es a n d ot h er s o urc e d oc u m e nts, will 
b e e nt er e d i n bl ac k or bl u e i n k, i niti al e d a n d d at e d b y t h e a ut h oriz e d p ers o n m a ki n g t h e 
c orr ecti o n/ a d diti o n.  C h a n g es will b e m a d e b y striki n g a si n gl e li n e t hr o u g h err o n e o us d at a, 
a n d  cl e arl y  e nt eri n g  t h e  c orr ect  d at a.    ( e. g.,  wr o n g  d at a  ri g ht  d at a).    E ntri es  m a y  n ot  b e 
er as e d or m as k e d wit h w hit e- o ut fl ui d.  If t h e r e as o n f or t h e c h a n g e is n ot a p p ar e nt, a bri ef 
ex pl a n ati o n f or t h e c h a n g e will b e writt e n a dj ac e nt t o t h e c h a n g e b y t h e cli nici a n. 
 
F or  tr a ns missi o n  t o  t h e  s p o ns or,  i nf or m ati o n  fr o m  t h e  st u d y  pr o gr ess  n ot es  a n d  ot h er 
s o urc e d oc u m e nts will b e pr o m ptl y e nt er e d i nt o t h e d at a b as e.  T h e d at a b as e als o c o nt ai ns 
a c o m pl et e a u dit tr ail t o c a pt ur e all r e g ul at or y c o m p o n e nts of d at a c orr ecti o ns ( e. g. i niti al 
e ntr y, n e w v al u e, i niti als a n d d at e of t h e c h a n g e). 
 
1 1. 2  
S o urc e D oc u m e nts 
 
S o urc e  d oc u m e nts  ar e  d efi n e d  as  t h e  r es ults  of  ori gi n al  o bs er v ati o ns  a n d  acti viti es  of  a 
cli nic al i n v esti g ati o n.  S o urc e d oc u m e nts will i ncl u d e, b ut ar e n ot li mit e d t o, pr o gr ess n ot es 
a n d  scr e e ni n g  l o gs.    All  s o urc e  d oc u m e nts  p ert ai ni n g  t o  t his  st u d y  will  b e  m ai nt ai n e d  b y 
t h e  i n v esti g at ors  a n d  m a d e  a v ail a bl e  f or  i ns p ecti o n  b y  a ut h oriz e d  p ers o ns.    T h e  ori gi n al 
si g n e d i nf or m e d c o ns e nt f or m f or e ac h p artici p ati n g s u bj ect s h all b e fil e d wit h r ec or ds k e pt 
b y t h e i n v esti g at ors a n d a c o p y gi v e n t o t h e s u bj ect. 
 
 
1 1. 3  
Fil e M a n a g e m e nt at t h e St u d y Sit e 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 4 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4 4   
 
It is t h e r es p o nsi bilit y of t h e i n v esti g at or t o e ns ur e t h at t h e st u d y c e nt er fil e is m ai nt ai n e d 
i n  acc or d a nc e  wit h  S ecti o n  8  of  t h e  I nt er n ati o n al  C o nf er e nc e  o n  H ar m o niz ati o n  (I C H) 
G ui d eli n e f or G o o d Cli nic al Pr actic es ( G C P).  
 
1 1. 4  
R ec or ds R et e nti o n at t h e St u d y Sit e 
 
F D A  r e g ul ati o ns  r e q uir e  all  i n v esti g at ors  p artici p ati n g  i n  cli nic al  dr u g  st u di es  t o  m ai nt ai n 
d et ail e d cli nic al d at a f or o n e of t h e f oll o wi n g p eri o ds: 
 
a)  A p eri o d of at l e ast t w o y e ars f oll o wi n g t h e d at e o n w hic h a N e w Dr u g A p plic ati o n is 
a p pr o v e d b y t h e F D A; 
b)  A  p eri o d  of  t w o  y e ars  aft er  t h e  s p o ns or  n otifi es  t h e  i n v esti g at or  t h at  n o  f urt h er 
a p plic ati o n is t o b e fil e d wit h t h e F D A. 
 
T h e i n v esti g at or m ust n ot dis p os e of a n y r ec or ds r el e v a nt t o t his st u d y wit h o ut eit h er ( 1) 
writt e n  p er missi o n  fr o m  t h e  s p o ns or  or  ( 2)  pr ovi di n g  a n  o p p ort u nit y  f or  t h e  s p o ns or t o 
c oll ect  s uc h  r ec or ds.    T h e  i n v esti g at or  s h all  t a k e  r es p o nsi bilit y  f or  m ai nt ai ni n g  a d e q u at e 
a n d  acc ur at e  el ectr o nic  or  h ar d  c o p y  s o urc e  d oc u m e nts  of  all  o bs erv ati o ns  a n d  d at a 
g e n er at e d  d uri n g  t his  st u d y,  i ncl u di n g  a n y  d at a  cl arific ati o n  f or ms  ( D C Fs)  r ec ei v e d  fr o m 
. S uc h d oc u m e nt ati o n is s u bj ect t o i ns p ecti o n b y t h e s p o ns or a n d  t h e F D A. 
 
 
1 2.  
Q U ALI T Y C O N T R OL A N D Q U ALI T Y A S S U R A N C E 
 
1 2. 1  
M o nit ori n g 
 
T h e  s p o ns or  h as  et hic al,  l e g al  a n d  sci e ntific  o bli g ati o ns  t o  c ar ef ull y f oll o w  t his  st u d y  i n  a 
d et ail e d  a n d  or d erl y  m a n n er  i n  acc or d a nc e  wit h  est a blis h e d  r es e arc h  pri nci pl es  a n d  F D A 
r e g ul ati o ns.    All  m e dic al  r ec or ds  (s o urc e  d oc u m e nts)  of  t h e  s u bj ects  p artici p ati n g  i n  t his 
st u d y  m ust  b e  pr es e nt e d  f or  r e vi e w  a n d  v erific ati o n  of  e C R Fs.  M o nit ors  m ust  b e  gi v e n 
dir ect acc ess t o eit h er ori gi n al or c ertifi e d c o pi es of t h e m e dic al r ec or ds.   
 
 
1 2. 2  
A u diti n g 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
T h e  s p o ns or  ( or  r e pr es e nt ati v e)  m a y  c o n d uct  a u dits  at  t h e  st u d y  c e nt er(s).    A u dits  will 
i ncl u d e,  b ut  ar e  n ot  b e  li mit e d  t o,  dr u g  s u p ply,  pr es e nc e  of  r e q uir e d  d oc u m e nts,  t h e 
i nf or m e d  c o ns e nt pr oc ess,  a n d  c o m p aris o n of  c as e  r e p ort  f or ms  wit h  s o urc e d oc u m e nts.  
T h e  i n v esti g at or  a gr e es  t o  p artici p at e  wit h  a u dits  c o n d uct e d  at  a  r e as o n a bl e  ti m e  i n  a 
r e as o n a bl e m a n n er. 
 
R e g ul at or y a ut h oriti es w orl d wi d e m a y als o a u dit t h e i n v esti g at or d uri n g or aft er t h e st u d y. 
T h e i n v esti g at or s h o ul d c o nt act  t h e s p o ns or i m m e di at el y if n otifi e d of s uc h a n a u dit, a n d 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 5 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4 5   
 
m ust  f ull y  c o o p er at e  wit h  t h e  a u dits  c o n d uct e d  at  a  r e as o n a bl e  ti m e  i n  a  r e as o n a bl e 
m a n n er. 
 
 
1 3.  
E T HI C S A N D R E S P O N SI B ILI T Y 
 
T his  st u d y  m ust  b e  c o n d uct e d  i n  c o m pli a nc e  wit h  t h e  pr ot oc ol,  D ecl ar ati o n  of  H elsi n ki, t h e 
U nit e d  St at es  F o o d  a n d  Dr u g  A d mi nistr ati o n  ( F D A)  r e g ul ati o ns,  a n y  ot h er  c o u ntri es 
r e g ul ati o ns, a n d I C H G C P G ui d eli n es 
 
 
 
1 4.  
U S E O F I N F O R M A TI O N A N D P U BLI C A TI O N 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
All  i nf or m ati o n  s u p pli e d  b y  t h e  s p o ns or  i n  c o n n ecti o n  wit h  t his  st u d y  a n d  n ot  pr e vi o usl y 
p u blis h e d, is c o nsi d er e d c o nfi d e nti al i nf or m ati o n.  T his i nf or m ati o n i ncl u d es, b ut is n ot li mit e d 
t o,  d at a,  m at eri als  (i. e.  t h e  cli nic al  pr ot oc ol,  c as e  r e p ort  f or ms),  e q ui p m e nt,  ex p eri e nc e 
( w h et h er  of  a  sci e ntific,  t ec h nic al,  e n gi n e eri n g,  o p er ati o n al,  or  c o m m erci al  n at ur e),  d esi g ns, 
s p ecific ati o ns, k n o w- h o w, pr o d uct us es, pr oc ess es, f or m ul a e, c osts, fi n a nci al d at a, m ar k eti n g 
pl a ns  a n d  dir ect  s elli n g  s yst e ms,  c ust o m er  lists  a n d  t ec h nic al  a n d  c o m m erci al  i nf or m ati o n 
r el ati n g  t o  c ust o m ers  or  b usi n ess  pr oj ecti o ns  us e d  b y  t h e  s p o ns or  i n  its  b usi n ess.  A n y  d at a, 
i n v e nti o ns,  or  disc o v eri es  c oll ect e d  or  d e v el o p e d,  as  a  r es ult  of  t his  st u d y  is  c o nsi d er e d 
c o nfi d e nti al. T his c o nfi d e nti al i nf or m ati o n s h all r e m ai n t h e s ol e pr o p ert y of t h e s p o ns or, s h all 
n ot  b e  discl os e d  t o  a n y  u n a ut h oriz e d  p ers o n  or  us e d  i n  a n y  u n a ut h oriz e d  m a n n er  wit h o ut 
writt e n c o ns e nt of t h e s p o ns or, a n d s h all n ot b e us e d exc e pt i n t h e p erf or m a nc e of t h e st u d y.  
As s uc h, c o nfi d e nti al st u d y-r el at e d i nf or m ati o n s h o ul d n ot b e i ncl u d e d o n t h e c urric ul u m vit a e 
of a n y p artici p ati n g i n v esti g at or or st u d y st aff. 
 
T h e  i nf or m ati o n  d e v el o p e d  d uri n g  t h e  c o urs e  of  t his  cli nic al  st u d y  is  als o  c o nsi d er e d 
c o nfi d e nti al, a n d will b e us e d b y t h e s p o ns or i n c o n n ecti o n wit h t h e d e v el o p m e nt of t h e dr u g.  
T h e i nf or m ati o n m a y b e discl os e d as d e e m e d n ec ess ar y b y t h e s p o ns or t o all o w t h e us e of t h e 
i nf or m ati o n d eri v e d fr o m t his cli nic al st u d y, t h e i n v esti g at or is o bli g e d t o pr o vi d e t h e s p o ns or 
wit h   c o m pl et e  t est  r es ults  a n d  all  d at a  d e v el o p e d  i n  t h e  st u d y.  T h e  i nf or m ati o n  o bt ai n e d 
d uri n g  t his  st u d y  m a y  b e  m a d e  a v ail a bl e  t o  ot h er  i n v esti g at ors  w h o  ar e  c o n d ucti n g  si mil ar 
st u di es. 
 
T h e  i n v esti g at or  s h all  n ot  m a k e  a n y  p u blic ati o n  r el at e d  t o  t his  st u d y  wit h o ut  t h e  ex pr ess 
writt e n  p er missi o n  of  t h e  s p o ns or. 
 
  
 
  
 
  
  
  
  
  
  
 
  
 
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 6 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4 6   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I N V E S TI G A T O R A G R E E M E N T 
 
P R O T O C OL N U M B E R:  P R G- N Y -1 4 - 00 8  
 
P R O T O C OL TI TL E:  
A M ulti- C e nt er, D o u bl e- Bli n d, R a n d o miz e d V e hicl e- C o ntr oll e d, P ar all el- 
Gr o u p St u d y t o C o m p ar e P erri g o U K FI N C O’s
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 Ac ycl o vir Cr e a m, 5 % wit h 
Z O VI R A X ®  ( Ac ycl o vir)  Cr e a m  5 %,  a n d  b ot h  Activ e  Tr e at m e nts  t o  a 
V e hicl e C o ntr ol i n Tr e at m e nt of R ec urr e nt H er p es L a bi alis 
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 7 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4 7   
 
I  h a v e  c ar ef ull y  r e a d  t h e  f or e g oi n g  pr ot oc ol  a n d  a gr e e  t h at  it  c o nt ai ns  all  t h e  n ec ess ar y 
i nf or m ati o n f or c o n d ucti n g t his st u d y s af el y.  I will c o n d uct t his st u d y i n strict acc or d a nc e wit h 
t his pr ot oc ol, I C H G ui d eli n es f or G o o d Cli nic al Pr actic es, t h e C o d e of F e d er al R e g ul ati o ns, t h e 
H e alt h  I ns ur a nc e  P ort a bilit y  a n d  Acc o u nt a bilit y  Act  ( HI P A A)  a n d  a n y  l oc al  r e g ul at or y 
r e q uir e m e nts  a n d  will  att e m pt  t o  c o m pl et e  t h e  st u d y  wit hi n  t h e  ti m e  d esi g n at e d.    I  will 
pr o vi d e acc ess t o c o pi es of t h e pr ot oc ol a n d all ot h er i nf or m ati o n r el ati n g t o pr e-cli nic al a n d 
pri or  cli nic al  ex p eri e nc e  s u b mitt e d  b y  P erri g o t o  all  p ers o n n el  r es p o nsi bl e  t o  m e  w h o 
p artici p at e  i n  t h e  st u d y.    I  will  disc uss  t his  i nf or m ati o n  wit h  t h e m  t o  ass ur e  t h at  t h e y  ar e 
a d e q u at el y i nf or m e d r e g ar di n g t h e dr u g a n d c o n d uct of t h e st u d y.  I a gr e e t o k e e p r ec or ds o n 
all s u bj ect i nf or m ati o n i n acc or d a nc e wit h F D A r e g ul ati o ns. 
 
 
 
 
  
 
 
 
   Pri nci p al I n v esti g at or’s Pri nt e d N a m e  
 
 
 
 
  
 
 
 
   Pri nci p al I n v esti g at or’s Si g n at ur e  
 
 
 
  
 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
   D at e 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 8 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 4 8   
 
1 5.  
A P P E N DI C E S 
 
1 5. 1  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
     
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 9 of 2 1 9




Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 5 0   
 
  
 
 
  
 
 
 
   
5.  
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 5 1 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 5 1   
 
Pl e as e r e p ort a n y si d e eff ects or pr o bl e ms y o u h a v e wit h t h e st u d y m e dic ati o n t o y o ur st u d y 
c o or di n at or or t h e st u d y p h ysici a n at t h e s u bs e q u e nt visit 
 
 
Y o ur i niti al tr e at m e nt d ay is:   _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D a y 1, Visit 2)  
  
  
  
 
                            ( D at e) 
 
Y o u ar e sc h e d ul e d t o r et ur n at: 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 2, Visit 3)     
( Ti m e) 
( D at e) 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 3, Visit 4)  
( Ti m e)   
  
  
  
( D at e) 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 4, Visit 5 )  
( Ti m e)  
  
  
  
( D at e)  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 5, Visit 6 )  
( Ti m e)  
  
  
  
( D at e)  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 6, Visit 7 )  
( Ti m e)  
  
  
  
( D at e)  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 7, Visit 8 )  
( Ti m e)  
  
  
  
( D at e)  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 8, Visit 9 )  
( Ti m e)  
  
  
  
( D at e)  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 1 0 , Visit 1 0)  
( Ti m e)  
  
  
  
( D at e)  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 1 2, Visit 1 1)  
( Ti m e)  
  
  
  
( D at e)  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 5 2 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 5 2   
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 1 4, Visit 1 2 )  
( Ti m e)  
  
  
  
( D at e)  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ o n _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( D ay 2 1, Visit 1 3)  
( Ti m e)  
  
  
  
( D at e)  
 
 
 
ALL  A P P OI N T M E N T S  A R E  I M P O R T A N T!  I F  Y O U  N E E D  T O  R E- S C H E D UL E  Y O U R  A P P OI N T M E N T, 
PL E A S E C ALL Y O U R D O C T O R’ S O F FI C E I M M E DI A T EL Y.  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
N a m e a n d T el e p h o n e N u m b er of St u dy C o or di n at or/ St u dy Sit e 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 5 3 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 5 3   
 
1 5. 3  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 5 4 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 5 4   
 
 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 5 5 of 2 1 9


Pr ot oc ol N o: P R G- N Y -1 4 -0 0 8  
 
 
 
 
P a g e 5 5   
 
1 6.  
R E F E R E N C E S 
 
1.  J a m es,  Willi a m  D.;  B er g er,  Ti m ot h y  G.;  et  al.  ( 2 0 0 6).  A n dr e ws'  Dis e as es  of  t h e  S ki n: 
cli nic al D er m at ol o g y. S a u n d ers Els e vi er 
2.  F D A A p pr o v es N o n- Pr escri pti o n C ol d S or e T o pic al Tr e at m e nt D oc os o n al 1 0 % 
3.  S u m m ar y B asis of A p pr ov al Z o vir ax ® ®, Cr e a m ( Acycl o vir Cr e a m, 5 %) 
4.  P ac k a g e i ns ert Z o vir ax ® ® Cr e a m ( Ac ycl o vir) d at e d Oct 2 0 1 0. 
5.  w w w. Z o vir ax ®.c o m  
6.  O G D Dr aft G ui d a nc e o n Ac ycl o vir M arc h 2 0 1 2 
7.  S u m m ar y B asis of A p pr ov al X er es e ® ® ( Ac ycl o vir a n d Hy dr oc ortis o n e) Cr e a m 5 %/ 1 % 
8.  S pr u a nc e, SL, et. al. A nti micr o bi al A g e nts & C h e m ot h er a p y 4 6; 7: 2 2 3 8- 2 2 4 3 
9.  S u m m ar y B asis of A p pr ov al f or A br e v a ® ( d oc os a n ol) Cr e a m 1 0 % ( Gl ax o S mit h Kli n e), 
N D A # 2 0- 9 4 1. 
 
 
 
 
 
 
 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 5 6 of 2 1 9

SAP_001.pdf: 
 
 
NCT02265913 
 
04-22-2016 








Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 4 of 4 1 
                                                          C o nfi de nti al  
 
 
 
T a ble of C o nte nts 
1  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S .................................................... 6  
2  
I N T R O D U C TI O N .................................................................................................................. ............... 7 
3  
S T U D Y O B J E C TI V E S .............................................................................................................. ........... 8 
4  
S T U D Y D E SI G N .................................................................................................................. ................. 8 
4. 1  
G E N E R A L D E SI G N  ............................................................................................................................ 8 
4. 2  
D I S C U S SI O N O F S T U D Y D E SI G N  ...................................................................................................... 1 0 
4. 3  
M E T H O D O F A S SI G N M E N T O F S U BJ E C T S T O T R E A T M E N T G R O U P S  ................................................. 1 0 
4. 4  
B LI N DI N G  ....................................................................................................................................... 1 1 
4. 5  
D E T E R MI N A TI O N O F S A M P L E S I Z E ................................................................................................. 1 1 
5  
C H A N G E S I N T H E C O N D U C T O F T H E S T U D Y O R P L A N N E D A N A L Y S E S ........................ 1 2  
5. 1  
C H A N G E S I N T H E C O N D U C T O F T H E S T U D Y  .................................................................................... 1 2 
5. 2  
C H A N G E S F R O M T H E A N A L Y S E S P L A N N E D I N T H E P R O T O C O L / CI P ................................................ 1 2 
6  
B A S E LI N E, E F FI C A C Y A N D S A F E T Y E V A L U A TI O N S ............................................................ 1 3  
6. 1  
S C H E D U L E O F E V A L U A TI O N S  ......................................................................................................... 1 3 
6. 2  
T I M E P OI N T A L G O RI T H M S  .............................................................................................................. 1 5 
6. 2. 1  
Rel ative D ay .................................................................................................................. ........ 1 5 
6. 2. 2  
Le n gt h of Ti me-t o- E ve nt P ar a meters ..................................................................................... 1 5  
6. 2. 3  
Wi n d o ws ....................................................................................................................... ......... 1 5 
6. 3  
B A S E LI N E A S S E S S M E N T S  ............................................................................................................... 1 6 
6. 4  
E F FI C A C Y V A RI A B L E S  .................................................................................................................... 1 6 
6. 4. 1  
Pri m ary Effic acy E n d p oi nt – Ti me-t o- C o m plete He ali n g of Lesi o ns .................................... 1 7  
6. 4. 2  
Ot her Effic acy E n d p oi nt  – Lesi o n St a ges .............................................................................. 1 8 
6. 5  
S A F E T Y A S S E S S M E N T S  ................................................................................................................... 1 8 
6. 5. 1  
Exte nt of Ex p os ure a n d C o m pli a nce t o St u dy Tre at me nt ...................................................... 1 8  
6. 5. 2  
A dverse E ve nts ................................................................................................................ ...... 1 9 
6. 5. 2. 1  
Defi niti o ns ................................................................................................................... ..................... 1 9 
6. 5. 2. 2  
Classificati o ns of a d vers e e ve nts assess me nts ................................................................................. . 2 0 
6. 5. 3  
Cli nic al L a b or at ory Ev al u ati o ns – Uri ne Pre g n a ncy Test .................................................... 2 0  
6. 5. 4  
Ot her O bserv ati o ns Re l ate d t o S afety .................................................................................... 2 1 
6. 5. 4. 1  
P h ysical E xa mi nati o n .......................................................................................................... ............. 2 1 
6. 5. 4. 2  
Vital Si g ns ................................................................................................................... ..................... 2 1 
6. 5. 4. 3  
A p plicati o n Site R eacti o n Asess me nt ........................................................................................... .... 2 1 
6. 5. 4. 4  
Lesi o n S y m pt o ms ............................................................................................................... .............. 2 1 
7  
S T A TI S TI C A L M E T H O D S ........................................................................................................... .... 2 1 
7. 1  
G E N E R A L M E T H O D O L O G Y  ............................................................................................................. 2 1 
7. 2  
A DJ U S T M E N T S F O R C O V A RI A T E S  ................................................................................................... 2 2 
7. 3  
H A N D LI N G O F D R O P O U T S O R M I S SI N G D A T A ................................................................................. 2 2  
7. 4  
IN T E RI M A N A L Y S E S A N D D A T A M O NI T O RI N G  ................................................................................ 2 3 
7. 5  
M U L TI -C E N T E R S T U DI E S A N D P O O LI N G O F C E N T E R S  ..................................................................... 2 3 
7. 6  
M U L TI P L E C O M P A RI S O N S / MU L TI P LI CI T Y  ...................................................................................... 2 4 
7. 7  
U S E O F A N “ E F FI C A C Y S U B S E T ”  O F S U BJ E C T S ................................................................................ 2 4  
7. 8  
A C TI V E - CO N T R O L S T U DI E S IN T E N D E D T O S H O W E Q UI V A L E N C E  ................................................... 2 4 
7. 9  
E X A MI N A TI O N O F S U B G R O U P S  ....................................................................................................... 2 4
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 5 of 1 2 1




Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 6 of 4 1 
                                                          C o nfi de nti al  
 
 
 
 
1  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S 
 
T a ble 1: A b bre vi ati o ns a n d Defi niti o ns of Ter ms 
 
A E(s) 
A d verse e ve nt(s) 
A N O V A  
A nal ysis of varia nce 
A T C 
A nat o mical t hera pe utic c he mical 
B MI 
B o d y mass i n de x 
CI 
C o nfi de nce i nter val 
CI P 
Cli nical i n vesti gati o n pla n 
c m 
Ce nti meters 
C M H 
C oc hra n- Ma ntel- Hae nszel 
C S R 
Cli nical St u d y Re p ort 
e C R F 
Electr o nic case re p ort f or m 
E N T 
Ear, n ose, a n d t hr oat 
H 0 
N ull h y p ot hesis 
H 1 
Alter nati ve h y p ot hesis 
H S V 
Her pes si m ple x vir us 
I C F 
I nf or me d c o nse nt f or m  
I R A E 
I m me diatel y re p orta ble a d verse e ve nts  
I T T 
I nte nt-t o- Treat 
k g 
Kil o gra m 
Ma x 
Ma xi m u m 
Me d D R A  
Me dical Dicti o nar y  f or Re g ulat or y Acti vities 
Mi n 
Mi ni m u m 
mI T T 
M o difie d I nte nt-t o- Treat 
N 
N u m ber of s u bjects 
P P 
Per- Pr ot oc ol 
P T 
Preferre d ter m  
R H L 
Rec urre nt her pes la bialis 
S A E 
Seri o us a d verse e ve nt 
S A P 
Statistical a nal ysis pla n 
S A S  
Statistical a nal ysis s oft ware 
S O C 
S yste m or ga n class  
S D 
Sta n dar d De viati o n 
S O P 
Sta n dar d o perati n g pr oce d ures  
T C R 
T he ore m Cli nical Researc h 
T E A E 
Treat me nt-e mer ge nt a d verse e ve nt 
W H O 
W orl d Healt h Or ga nizati o n 
U NI X 
U Ni ple xe d I nf or mati o n a n d C o m p uti n g Ser vice  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 1 7 of 1 2 1








Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 1 0 of 4 1 
                                                          C o nfi de nti al  
 
 
 
 
4. 2  
Disc ussi o n of St u d y Desi g n 
 
T his st u d y is desi g ne d t o de m o nstrate t he bi oe q ui vale nce of Perri g o’s Ac ycl o vir Crea m, 
5 % t o Valea nt’s Z o vira x ®  Crea m 5 % a n d will als o de m o nstrate t he s u peri orit y of efficac y 
of  Perri g o’s  Ac ycl o vir  Crea m,  5 %  a n d  Valea nt’s  Z o vira x ®   Crea m  5 %  o ver  Perri g o’s 
Ve hicle of Ac ycl o vir Crea m, 5 %. T his st u d y has t he f oll o wi n g desi g n c haracteristics: 
 
 Ra n d o mize d: T his is d o ne i n or der t o eli mi nate t he all ocati o n bias a n d bala nci n g 
b ot h k n o w n a n d u n k n o w n pr o g n ostic fact ors, i n t he assi g n me nt of treat me nts. 
 
 Ve hicle c o ntr ol ( Place b o): T his st u d y i n v ol ves a Ve hicle gr o u p t hat will be use d 
t o de m o nstrate t he s u peri orit y of t he test a n d refere nce f or m ulati o ns. 
 
 Bi oe q ui vale nce: T o esta blis h bi oe q ui val e nce bet wee n Perri g o's Ac ycl o vir Crea m, 
5 %  (test)  a n d  Valea nt's  Z o vira x ®   Crea m  5 %  (refere nce),  t he  9 0 %  c o nfi de nce 
i nter val of t he test/refere nce rati o f or t he pri mar y e n d p oi nt, ti me-t o lesi o n heali n g, 
m ust be c o ntai ne d wit hi n [ 0. 8 0, 1. 2 5]  
 
 S u peri orit y: As per t he F D A g ui deli nes, if bi oe q ui vale nce is de m o nstrate d f or test 
a n d  refere nce  f or m ulati o ns,  t his  will  o nl y  be  acce pte d  if  t he  st u d y  ha d  a de q uate 
se nsiti vit y t o detect tr ue differe nces bet wee n f or m ulati o ns if t he y e xiste d. He nce, 
t his  st u d y  is  desi g ne d  t o  de m o nstrate  t he  s u peri orit y  of  Perri g o’s  Ac ycl o vir 
Crea m, 5 % a n d Valea nt’s Z o vira x ®  Crea m 5 % o ver Perri g o U K FI N C O’s Ve hicle 
of Ac ycl o vir Crea m, 5 %. 
 
4. 3  
Met h o d of Assi g n me nt of S u bj ects t o Tre at me nt Gr o u ps 
 
Eli gi ble s u bjects will be ra n d o mize d t o o ne of t he f oll o wi n g treat m e nt gr o u ps i n a 1: 1: 1 
all ocati o n rati o: 
 
 Test F or m ulati o n: Ac ycl o vir Crea m, 5 % - Perri g o  
 
 Refere nce F or m ulati o n: Z o vira x ®  Crea m 5 % - Valea nt P har mace uticals 
 
 Ve hicle: Ve hicle of Ac ycl o vir Crea m, 5 % - Perri g o 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
Ra n d o mizati o n  will  be  perf or me d  acc or di n g t o  a  c o m p uter- ge nerate d  ra n d o mizati o n 
sc he me w here t he treat me nt gr o u p desi g nati o n has bee n assi g ne d t o t he s u bject n u m ber. 
T he  treat me nt  desi g nati o n  will  re mai n  bli n de d  u ntil  t he  fi nal  data base  is  l oc ke d.  A n 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 2 1 of 1 2 1












Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 1 6 of 4 1 
                                                          C o nfi de nti al  
 
 
 
Data will be s u m marize d as per sc he d ule d st u d y visits o nl y. N o wi n d o wi n g of visits will 
be perf or me d f or data a nal ysis. 
 
T a ble 3: Cli nic Visit Wi n d o w 
 
Visit 
Sc he d ule d St u d y D a y 
Pr ot oc ol Visit Wi n d o w  
Visit 2 ( Da y 1)  
T he date of i nitial a p plicati o n   
Da y 1 
Visit 3 ( Da y 2)  
Da y 2 ( wit hi n 2 4 h o urs of treat me nt 
i nitiati o n) 
Da y 2 ( wit hi n 2 4 h o urs of treat me nt 
i nitiati o n) 
Visit 4 ( Da y 3)  
Da y 3 
Da y 3 
Visit 5 ( Da y 4)  
Da y 4  
Da y 4 
Visit 6 ( Da y 5)  
Da y 5  
Da y 5 
Visit 7 ( Da y 6)  
Da y 6  
Da y 6 
Visit 8 ( Da y 7)  
Da y 7 
Da y 7 
Visit 9 ( Da y 8)  
Da y 8 
Da y 8 
Visit 1 0 ( Da y 1 0)  
Da y 1 0 
Da y 1 0 
Visit 1 1 ( Da y 1 2)  
Da y 1 2  
Da y 1 2 
Visit 1 2 ( Da y 1 4)  
Da y 1 4 
Da y 1 3 - 1 5 
Visit 1 3 ( Da y 2 1)  
Da y 2 1 
Da y 1 9 - 2 3 
 
6. 3  
B aseli ne Assess me nts 
 
Baseli ne assess me nts will be t he last assess me nt pri or t o t he date of t he i nitial a p plicati o n 
of  t he  st u d y  me dicati o n. 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
6. 4  
Effic ac y V ari a bles 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
T he  pri mar y  efficac y  e n d p oi nt  is  t he  ti me  of   c o m plete  heali n g  of  lesi o n.  C o m plete 
heali n g  ( defi ne d  as  l oss  of  cr ust  a n d  re-e p it helializati o n  wit h  or  wit h o ut  er yt he ma,  as 
assesse d b y t he i n vesti gat or, base d o n b ot h cli n ical o bser vati o n a n d re vie w of t he s u bject 
diar y) is meas ure d i n da ys fr o m t he ti me of  first d osi n g.  Ti me-t o-c o m plete lesi o n heali n g 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 2 7 of 1 2 1








Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 2 0 of 4 1 
                                                          C o nfi de nti al  
 
 
 
me dicati o n,  t he  I n vesti gat or’s  Br oc h ure,  or  as   descri be d  i n  t he  cli nical  pr ot oc ol  a n d 
c o nse nt materials. 
 
Tre at me nt e mer ge nt a d verse e ve nt ( T E A E)  
Treat me nt-e mer ge nt a d verse e ve nts ( T E A E) ar e a n y A Es t hat occ ur or w orse n (i ncrease 
i n  se verit y  a n d/ or  fre q ue nc y)  d uri n g  or after  t he  i nitial  a p plicati o n  of  t he  st u d y 
me dicati o n. 
 
F or treat me nt-e mer ge nt stat us re gar di n g e ve nts  wit h partial or missi n g dates, please refer 
t o Secti o n 7. 3. 
 
6. 5. 2. 2  Cl assific ati o ns of a dverse eve nts assess me nts 
 
I nte nsit y of a d verse e ve nts 
T he  ma xi m u m  i nte nsit y  of  a n  A E  d uri n g  a  da y  will  be  rec or de d  o n  t he  e C R F.  T he 
i nte nsit y of a n A E will be gra de d as f oll o ws: 
 Mil d  
 M o derate  
 
Se vere  
 
F or  A Es  wit h  u n k n o w n  or  missi n g  se verit y,  a val ue  of  " Se vere"  will  be  i m p ute d  f or 
s u m mar y a nal yses. 
 
C a us al Rel ati o ns hi p t o St u d y Me dic ati o n 
Ca usal relati o ns hi p of A E t o st u d y me dicati o n will be classifie d b y t he I n vesti gat or a n d 
will be re p orte d as f oll o wi n g:  
 
 Defi nitel y relate d 
 Pr o ba bl y relate d 
 P ossi bl y relate d 
 U nli kel y relate d 
 N ot relate d 
 
A n  A E  will  be  c o nsi dere d  relate d  t o   st u d y  me dicati o n  if  t he  relati o ns hi p  is  defi nitel y 
relate d,  pr o ba bl y  relate d,  or  p ossi bl y  relate d.  A n y  missi n g  ( u n k n o w n  or  missi n g)  ca usal 
relati o ns hi p of a n A E t o st u d y me dicati o n will be s u m marize d as relate d. 
 
6. 5. 3  Cli nic al L a b or at or y E v al u ati o ns – Uri ne Pre g n a nc y Test 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
Fe males of c hil d beari n g p ote ntial  will ha ve a uri ne pre g na nc y test at Visit 1( Scree ni n g), 
Visit 2 ( Da y 1), Visit 1 3 ( Da y 2 1) a n d at t he E n d of St u d y visit.  
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 1 of 1 2 1


Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 2 1 of 4 1 
                                                          C o nfi de nti al  
 
 
 
6. 5. 4  Ot her O bser v ati o ns Rel ate d t o S afet y 
6. 5. 4. 1  P hysic al Ex a mi n ati o n  
 
T he p h ysical e xa mi nati o n i ncl u des ear, n ose a n d t hr oat ( E N T), h eart, l u n g a n d a b d o me n 
e val uati o n, a n d will be perf or me d at Vis it 1 ( Scree ni n g) a n d Visit 2 ( Da y 1). 
 
6. 5. 4. 2  Vit al Si g ns  
 
T he  vital  si g ns  i ncl u de  sitti n g  bl o o d  press ure ,  oral  te m perat ure,  heart  rate,  res pirat or y 
rate, hei g ht a n d wei g ht, a n d will be perf or me d at Visit 1 ( Scree ni n g) a n d Visit 2 ( Da y 1).  
 
6. 5. 4. 3  A p plic ati o n Site Re acti o n Asess me nt 
 
T he a p plicati o n site reacti o n s u c h as dr y li ps, des q ua mati o n, dr y ness of s ki n, crac ke d li ps, 
b ur ni n g s ki n, pr urit us, fla ki ness of s ki n a n d s ti n gi n g of t he s ki n will be assesse d as N o ne, 
Mil d, M o derate a n d Se vere at Visit 2 ( D a y 1) a n d at eac h s u bse q ue nt visit. 
 
A p plicati o n site reacti o ns  will n ot t o be c o nsi dere d as a d verse e ve nts u nless t he y warra nt 
te m p orar y  disc o nti n uati o n  of  t he  st u d y  me dicati o n,  disc o nti n uati o n  fr o m  t he  st u d y  or 
treat me nt wit h ne w co nc o mita nt me dicati o n.  
 
6. 5. 4. 4  Lesi o n Sy m pt o ms 
 
Lesi o n s y m pt o ms will be c ollecte d via s u bject diaries.  
 
7  
S T A TI S TI C A L M E T H O D S 
7. 1  
Ge ner al Met h o d ol o g y 
 
All a nal ysis will be perf or me d after t he data base is l oc ke d a n d access has bee n re m o ve d 
fr o m t he data base a n d t he stu d y treat me nt c o des are u n bli n de d. 
 
All statistical tests will be t w o- si de d wit h a si g nifica nce le vel of 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
= 0. 0 5, u nless s pecifie d 
ot her wise.  
 
Data  will  be  s u m marize d  usi n g  descri pti ve  statistics  ( n u m ber  of  s u bjects  [ n],  mea n, 
sta n dar d de viati o n [ S D], me dia n, mi ni m u m, a n d ma xi m u m) f or c o nti n u o us varia bles a n d 
fre q ue nc y a n d perce nta ge f or discrete varia bles.  
 
F or t he p ur p ose of dis pla y, t he s u m mar y res ults will be r o u n de d as f oll o ws: 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 2 of 1 2 1














Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 2 8 of 4 1 
                                                          C o nfi de nti al  
 
 
 
8. 4  
De m o gr a p hic a n d Ot her B a seli ne C h ar acteristics 
 
De m o gra p hic a n d baseli ne c haract eristics will be s u m marize d usi n g I nte nt-t o- Treat (I T T) 
P o p ulati o n b y treat me nt gr o u ps. 
 
A ge  ( years),  hei g ht  at  scree ni n g  (c m),  b o d y wei g ht  at  scree ni n g  ( k g),  a n d  b o d y  mass 
i n de x  ( B MI)  at  scree ni n g  i n  k g/ m2  will  be  s u m marize d  usi n g  descri pti ve  statistics  a n d 
ge n der, race, a n d et h nicit y will be s u m marize d usi n g fre q ue ncies a n d perce nta ges. 
 
Me dical  hist or y  will  be  s u m marize d  b y  fre q ue ncies  a n d  perce nta ges  of  s u bjects  b y 
s yste m  or ga n  class  ( S O C)  a n d  preferre d  ter m  ( P T),  wit hi n  S O C  a n d  P T  s orte d  b y 
desce n di n g fre q ue ncies. S u bjects wit h m ulti ple  e ve nts f or t he sa me S O C or P T, will be 
c o u nte d  o nl y  o nce  f or  t hat  S O C  or  P T.  Me di cal  hist or y  will  be  c o de d  usi n g  Me d D R A 
versi o n 1 9. 0. 
 
Birt h c o ntr ol met h o ds will be s u m marize d b y fre q ue ncies a n d perce nta ges. 
 
All  de m o gra p hic  a n d  baseli ne  c haracteristic s  descri be d  wit hi n  t his  secti o n  will  be 
prese nte d i n s u bject listi n gs. 
 
8. 5  
Pri or a n d C o nc o mit a nt T her a p y  
 
T he  W orl d  Healt h  Or ga nizati o n  ( W H O)  Dr u g  Di cti o nar y  ( Marc h  2 0 1 6) will  be  use d  t o 
classif y  pri or  a n d  c o nc o mita nt  me dicati o ns  b y  Preferre d  Na me  a n d  W H O  a nat o mical 
t hera pe utic c he mical ( A T C) classificati o n of i n gre die nts. 
 
Pri or  me dicati o ns  are  defi ne d  as  a n y  me dica ti o n  gi ve n  pri or  t o  a n d  st o p pe d  bef ore  t he 
i nitial  a p plicati o n  of  st u d y  me dicati o n.  C o nco mita nt  me dicati o ns  are  defi ne d  as  a n y 
me dicati o n  gi ve n  t o  t he  s u bject  starti n g  o n  or after  t he  da y  of  t he  i n itial  a p plicati o n  of 
st u d y  me dicati o n  or  starte d  pri or  t o  t he  i nitial  a p plicati o n  of  st u d y  me dicati o n  a n d 
c o nti n ui n g d uri n g t he st u d y. 
 
If t he start date of me dicati o n is u n k n o w n a n d t he e n d date is k n o w n, t he n t he me dicati o n 
will be c o nsi dere d: 
 
 Pri or t o st u d y me dicati o n if t he e n d date is pri or t o t he i nitial a p plicati o n of t he 
st u d y me dicati o n 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
C o nc o mita nt  t o  st u d y  me dicati o n  if  t he  e n d date  is  eit her  o n  or  after  t he  i nitial 
a p plicati o n of st u d y me dicati o n or t he e n d date is u n k n o w n. 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 3 9 of 1 2 1


Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 2 9 of 4 1 
                                                          C o nfi de nti al  
 
 
 
If b ot h t he start a n d e n d dates are u n k n o w n, t he n t he me dicati o n will be c o nsi dere d t o be 
“c o nc o mita nt  o n-treat me nt”.    T he  partial  a n d  c o m pletel y  missi n g  dates  f or  pri or  a n d 
c o nc o mita nt me dicati o ns will be i m p ute d as me nti o ne d i n secti o n 7. 3. 
 
Pri or a n d c o nc o mita nt me dicati o n will be s u m m arize d b y fre q ue ncies a n d perce nta ges of 
s u bjects b y preferre d na me wit hi n eac h A T C, wit h A T C a n d preferre d na mes s orte d b y 
desce n di n g fre q ue nc y. 
 
A T C  classificati o n  le vel  2  wi ll  be  use d  i n  s u m mar y  ta bles  a n d  listi n gs.  If  A T C 
classificati o n le vel 2 is missi n g, t he n A T C classificati o n le vel 1 will be use d.  
 
A s u bject listi n g of pri or a n d c o nc o mita nt me dicati o ns will be prese nte d. 
 
8. 6  
A n al ysis of Effic ac y P ar a meters 
8. 6. 1  E q ui v ale nce of Cli nic al E n d p oi nt A n al ysis 
 
T he  pri mar y  efficac y  a nal ysis  is  t o  de m o ns trate  t hat  Ac ycl o vir  Crea m,  5 %  -  Perri g o 
( Test) is bi oe q ui vale nt t o Z o vira x®  Crea m 5 % - Valea nt P har mace uticals ( Refere nce).  
 
T he h y p ot hesis t o test bi oe q ui vale nce of Test f or m ulati o n t o Refere nce f or m ulati o n will 
be: 
 
H 0 ( n ull h y p ot hesis): μ  T / μ  R ≤ 0. 8 0 or μ T / μ  R ≥1. 2 5  
vers us 
H 1 (alter nati ve h y p ot hesis): 0. 8 0 < μ  T / μ R  < 1. 2 5 
 
W here, μ T : T he mea n ti me-t o-c o m plete heali n g of t he lesi o n i n t he test treat me nt (i.e. 
Ac ycl o vir Crea m, 5 % - Perri g o) 
 
μ R : T he mea n ti me-t o-c o m plete heali n g of t he lesi o n i n t he refere nce treat me nt 
(i.e. Z o vira x Crea m 5 % - Valea nt P har mace uticals) 
 
T he  test  f or m ulati o n  (i.e.  Ac ycl o vir  Crea m,  5 %  -  Perri g o)  will  be  c o nsi dere d  as 
bi oe q ui vale nt  t o  t he  refere n ce  f or m ulati o n  (i.e.  Z o vira x ®
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
  Crea m  5 %  -  Valea nt 
P har mace uticals)  if  t he  9 0 %  c o nfi de nce  i nter v al  ( CI)  f or  t he  rati o  of  t he  mea ns  or 
me dia ns ( Test/ Refere nce) falls wi t hi n t he i nter val of 0. 8 0 t o 1. 2 5. 
 
T he mea n ti me-t o-c o m plete heal i n g of Test a n d Refere nce pro d uct will be a nal yze d usi n g 
A nal ysis of Varia nce ( A N O V A) wit h treat me nt a n d ce nter as fi xe d effects i n t he m o del. 
T he  9 0 %  c o nfi de nce  i nter val  f or  t he  rati o ( Test/ Refere nce)  of  mea n  ti me-t o-c o m plete 
heali n g will be o btai ne d b y Fieller’s met h o d.  
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 0 of 1 2 1










Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 3 4 of 4 1 
                                                          C o nfi de nti al  
 
 
 
Als o, t he fre q ue ncies a n d perce nta ges of s u bj ects w h o misse d m ore t ha n fi ve c o nsec uti ve 
a p plicati o ns of st u d y me dicat i o ns will be s u m marize d. 
 
8. 7. 1. 3  St u dy Me dic ati o n Dis pe ns ati o n 
 
A s u bject listi n g will be pr ese nte d w hic h will i ncl u de: 
 
 W het her s u bject was ra n d o mize d a n d st u d y me dicati o n was dis pe nse d? ( Yes/ N o) 
 Date of ra n d o mizati o n 
 Kit n u m ber 
 W het her  tear- off  la bel  was  affi xe d  t o   t he  st u d y  me dicati o n  dis pe nsi n g  l o g? 
( Yes/ N o) 
 N u m ber of t u bes dis pe nse d? ( 1 or 2) 
 W het her all t he dis pe nse d t u be s were c ollecte d? ( Yes/ N o) 
 W het her  t he  s u bject  diar y  a n d  i nstr ucti o ns  were  dis pe nse d/re vie we d  wit h  t he 
s u bject? ( Yes/ N o) 
 
8. 7. 2  A d verse E ve nts 
 
All A E s u m mar y ta bles will i ncl u de o nl y T E A Es u nless ot her wise n ote d.  
A d verse e ve nts will be s u m marize d b y s yste m or ga n class a n d preferre d ter m. A s u bject 
will o nl y be c o u nte d o nce per s yste m or ga n cl ass a n d preferre d ter m. A E’s will als o be 
prese nte d b y se verit y gra des. I n t he case of m ulti ple e x perie nces wit h t he sa me A E, t he 
s u bject will be c o u nte d o nl y o nce u n der t he w orst re p orte d se verit y. 
 
A d verse e ve nts will be prese nte d i n decreasi n g or der of t he i nci de nces at S O C le vel a n d 
wit hi n eac h S O C, i n decreasi n g or der of t he i nci de nces at t he preferre d ter m le vel. 
 
A n o verall s u m mar y of a d verse e ve nts will be prese nte d a n d will i ncl u de: 
 
 at least o ne T E A E 
 a n y se vere T E A E 
 a n y treat me nt-relate d T E A E 
 a n y seri o us T E A E 
 a n y seri o us treat me nt-relate d T E A Es 
 a n y T E A E res ulti n g i n deat h 
 a n y T E A E res ulti n g i n st u d y me dicat i o n i nterr u pti o n/ disc o nti n uati o n 
 a n y u ne x pecte d a d verse e ve nt 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
a n y T E A Es of i nterest 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 5 of 1 2 1


Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 3 5 of 4 1 
                                                          C o nfi de nti al  
 
 
 
T he  s u bjects’  fre q ue ncies  a n d  perce nta ges  wi ll  be  prese nte d  b y  s yste m  or ga n  class  a n d 
preferre d ter m f or t he f oll o wi n g: 
 
 All T E A Es 
 T E A Es b y se verit y 
 Treat me nt-relate d T E A Es 
 T E A Es lea di n g t o st u d y me dica ti o n i nterr u pti o n/ disc o nti n uati o n 
 Treat me nt-relate d T E A Es lea di n g t o st u d y me dicati o n 
i nterr u pti o n/ disc o nti n uati o n 
 Seri o us T E A Es 
 Seri o us treat me nt-relate d T E A Es 
 U ne x pecte d a d verse e ve nts 
 T E A Es of i nterest 
 
T he  o verall  e ve nt  c o u nts  will  als o  be  prese n te d  f or  t he  a b o ve  me nti o ne d  a d verse  e ve nt 
para meters. 
 
T he f oll o wi n g s u bject listi n gs will be prese nte d: 
 
 all A Es  
 S A Es 
 A Es lea di n g t o st u d y me dicati o n i nterr u pti o n/ disc o nti n uati o n 
 A Es lea di n g t o deat h 
 
8. 7. 3  Cli nic al L a b or at or y E v al u ati o ns – Uri ne Pre g n a nc y Test 
 
Fe males of c hil d beari n g p ote ntial  will ha ve a uri ne pre g na nc y test at Visit 1( Scree ni n g), 
Visit 2 ( Da y 1), Visit 1 3 ( Da y  2 1) a n d at t he E n d of St u d y. T his will be prese nte d i n a 
s u bject listi n g. 
 
8. 7. 4  Ot her O bser v ati o ns Rel ate d t o S afet y 
 
8. 7. 4. 1  P hysic al Ex a mi n ati o n  
 
T he p h ysical e xa mi nati o n will be perf or me d at Visit 1 ( Scree ni n g) a n d Visit 2 ( Da y 1). A 
s u bject listi n g will be prese nte d w hic h will i ncl u de: 
 
 W het her p h ysical e xa mi nati o n was perf or me d? ( Yes/ N o) 
 E xa mi nati o n date 
 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
Were t here a n y a b n or mal fi n di n gs? ( Yes/ N o) 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 6 of 1 2 1


Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 3 6 of 4 1 
                                                          C o nfi de nti al  
 
 
 
 
8. 7. 4. 2  Vit al Si g ns 
 
Vitals si g ns will be perf or me d at Visit 1 ( S cree ni n g) a n d Visit 2 ( Da y 1). 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 
 
8. 7. 4. 3  A p plic ati o n Site Re acti o n Asess me nt 
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
 
T he  se verit y  ( n o ne,  mil d,  m o derate  a n d  se ve re)  of  a p plicati o n  site  reacti o n  will  be 
s u m marize d b y fre q ue ncies an d perce nta ges b y visit.  
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 7 of 1 2 1


Perri g o C o m pa n y 
P R G- N Y- 1 4- 0 0 8 
 
Statistical A nal ysis Pla n 
 
 
                                                      
 
Pa ge 3 7 of 4 1 
                                                          C o nfi de nti al  
 
 
 
9  
C O M P U T E R S O F T W A R E 
 
All a nal yses will be perf or me d b y T he ore m C li nical Researc h usi n g Versi o n 9. 2 of S A S 
s oft ware  or  hi g her  wit hi n  a  U Ni ple xe d  I nf or mati o n  a n d  C o m p uti n g  Ser vice  ( U NI X) 
e n vir o n me nt. All s u m mar y ta bles a n d data listi n gs will be pre pare d usi n g S A S  s oft ware.  
 
1 0  R E F E R E N C E S 
 
1.  Efr o n, B., 1 9 8 7, " Better B o otstra p C o nf i de nce I nter vals ( wit h disc ussi o n)", 
J o ur n al of t he A meric a n St atistic al Ass oci ati o n , 8 2: 1 7 1- 2 0 1. 
 
2.  Efr o n B ( 1 9 7 9). B o otstra p met h o ds: a n ot her l o o k at t he jac k k nife. A n n. Statist. 7, 
1- 2 6. 
 
3.  Efr o n, B. a n d Ti bs hira ni, R. J. ( 1 9 9 3). A n I ntr o d ucti o n t o t he B o otstr a p.  C ha p ma n 
& Hall, B oca Rat o n. 
 
4.  V. H. Fra nz, 2 0 0 7, “ Rati os: a s h ort g ui de t o c o nfi de nce li mits a n d pr o per use”, 
U ni versit y of Giesse n, Gi esse n, Ger ma n y, Oct o ber 2 0 0 7. 
 
5.   Na nc y Bar ker, “ A Practical I ntr o d ucti n t o t he B o otstra p Usi n g t he S A S S yste m”, 
O xf or d P har mace utical Scie nces, Walli n gf or d, U K. 
 
6.  M ot uls k y, “I nt uiti ve Bi ostatistics”, p. 2 8 5- 2 8 6. 
 
7.  Na nc y Bar ker, “ A Practical I ntr o d ucti n t o  t he B o otstra p Usi n g t he S A S S yste m”, 
O xf or d P har mace utical Scie nces, Walli n gf or d, U K. 
 
8.  Draft G ui da nce o n Ac ycl o vir, Office  of Ge neric Dr u gs, F D A, Mar 2 0 1 2 
 
9.  Draft G ui da nce o n Ac ycl o vir, Office  of Ge neric Dr u gs, F D A, Dec 2 0 1 4 
 
1 0.  
Perri g o U K Fi nc o Li mite d Part ners hi p 
Cli nical St u d y Re p ort P R G- N Y- 1 4- 0 0 8
St o kes M. E., Da vis C. S., a n d K oc h G. G.  Cate g orical Data A nal ysis usi n g t he 
S A S S yste m. S A S I nstit ute I nc., 2 0 0 0: 1 7 7- 1 7 9. 
 
Ac ycl o vir Crea m 5 % 
C O N FI D E N TI A L
Pa ge 4 8 of 1 2 1