Conditions: Candida Vulvovaginitis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 186
Healthy volunteers: no

Brief summary:
This is a multicenter, randomized, double-blind, double-dummy, active-controlled, dose-finding study to compare the efficacy, safety and tolerability of oral SCY-078 versus oral fluconazole in adult female subjects 18 years and older with moderate to severe Acute Vulvovaginal Candidiasis (AVVC). Approximately 180 eligible subjects (30 subjects per treatment group) will be enrolled and randomized into the study.

Detailed description:
This is a Phase 2, multicenter, randomized, double-blind, double-dummy, active-controlled, dose-ranging study of female subjects with moderate to severe Acute Vulvovaginal Candidiasis. Subjects will be randomized to either the investigational arm (SCY-078) with 5 different dose regiments ranging from 1 to 3 days of treatment or to the active-control arm (fluconazole) for 1 day of treatment. After randomization subjects may be seen on study Day 3 (on site visit for PK subjects) , Day 10 (±2,) and Day 25 (+4).

Arms:
arm 1: 150 mg/day for 1 day arm 2: 750mg QD for 1 day only arm 3: 300mg BID for 1 day only arm 4: 450mg BID for 1 day only arm 5: 150mg BID for 3 days arm 6: 300mg BID for 3 days

Interventions: intervention 1: Fluconazole intervention 2: SCY-078
Intervention descriptions: intervention 1: Oral Antifungal comparator intervention 2: Investigational Antifungal

Protocol document:
SAP_002.pdf: 




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1 1. 9. 2  
Sec o n d ar y Effic ac y A n al yses .................................................................................... 1 4  
1 1. 9. 3  
E x pl or at or y Effic ac y A n al yses.................................................................................. 1 4  
1 1. 1 0  
S af et y A n al ysis ........................................................................................................... 1 4  
1 1. 1 0. 1  
A d verse E ve nts  ........................................................................................................... 1 5 
1 1. 1 0. 2  
Cli nic al L a b or at or y Te sti n g ...................................................................................... 1 5 
1 1. 1 0. 3  
Vit al Si g ns  ................................................................................................................... 1 6 
1 1. 1 1  
P h ar m a c o ki netics  ....................................................................................................... 1 6 
1 2.  C H A N G E S F R O M T H E P R O T O C O L A N D P L A N N E D A N A L Y S E S  ......................... 1 6 
1 3.  H E A DI N G S  .......................................................................................................................... 1 6 
1 4.  A R C HI VI N G A N D R E T E N TI O N O F D O C U M E N T S  .................................................... 1 6 
1 5.  O U T LI N E O F P R O P O S E D T A B L E S, LI S TI N G S A N D FI G U R E S  .............................. 1 7 
 


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List of A b bre vi ati o ns a n d Defi niti o ns of Ter ms 
A b bre vi ati o n  
Defi niti o n  
A E  
A d verse E ve nt  
A U C  
A rea u n der t he c o nce ntratio n -ti me c ur ve 
A V V C  
Ac ute V ul v o va gi nal Ca n di diasis  
BI D  
t wice dail y 
C F R  
C o de of Fe deral Re g ulati o ns  
C ma x  
Ma xi m u m c o nce ntrati o n  
C R F  
Case Re p ort F or m  
C R O  
C o ntract Researc h Or ga nizati o n  
D M P  
Data Ma na ge me nt Pla n  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
G C P  
G o o d Cli nical Practices  
G L P  
G o o d La b orat or y Practices  
I C F  
I nf or me d C o nse nt F or m  
I C H  
I nter nati o nal C o nfere nce o n Har m o nizati o n  
I P  
I n vesti gati o nal Pr o d uct  
I R B  
I nstit uti o nal Re vie w B oar d  
I T T  
I nte nti o n T o Treat  
L O C F  
Last O bser vati o n  Carrie d F or war d  
mI T T  
M o difie d I nte nti o n T o Treat  
O G D  
Office of Ge neric Dr u gs  
PI  
Pri nci pal I n vesti gat or  
P P  
Per Pr ot oc ol  
P K  
P har mac o ki netic  
Q D  
o nce dail y  
S D  
Sta n dar d De viati o n  
S A E  
Seri o us A d verse E ve nt  
S A S  
Statistical A nal yzi n g S yste m   
S O P  
Sta n dar d O perati n g Pr oce d ure  
T O C  
T est of c ure 
V S S  Scale  
V ul v o va gi nal Si g ns a n d S y m pt o ms  Scale  
 
 


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1.  I N T R O D U C TI O N 
T his Statistical A nal ysis Pla n ( S A P) is base d o n t he st u d y Pr ot oc ol A m e n d me nt 1 ( V ersi o n 2. 0) 
date d 1 3 J ul 2 0 1 7. 
T his  d oc u me nt  pr o vi d es  a d diti o nal  details  c o ncer ni n g  t he  statistical  a nal yses  o utli ne d  i n  t he 
pr ot oc ol a n d reflects a n y c ha n ges t o t he pr ot oc ol fr o m a n y a me n d me nts. T his pla n will n ot re peat 
all  t he  defi niti o ns  gi ve n  i n  t he  pr ot oc ol  b ut  will  pr o vi de  f urt her  details  of  t he  s u m maries  a n d 
a nal ys es pla n ne d t h erei n.  
2.  S T U D Y O B J E C TI V E S  
Pri mar y O bj ecti ve:  
•  T o i de ntif y t h e r ec o m me n de d d ose of oral S C Y -0 7 8 i n s u bjects wit h m o d erate t o se vere 
Ac ute  V ul v o va gi nal  Ca n di diasis  ( A V V C ) b y  c o m pari n g  t he  efficac y  of  differe nt  d ose 
le vels a n d d osi ng re gi me ns of oral S C Y - 0 7 8 
Sec o n dar y O bj ecti ves:  
•  T o e val uate t he effi cac y of oral S C Y -0 7 8 i n s u bjects wit h A V V C base d o n m yc ol o gical 
a n d cli nical o utc o mes  
•  T o e val uate t h e saf et y a n d t olera bilit y of differe nt d ose le vels a n d d osi n g re gi me ns of oral 
S C Y - 0 7 8 i n s u bjects wit h A V V C 
E x pl orat or y O bjecti ves: 
•  T o  e x pl ore  t he  efficac y  of  S C Y -0 7 8  i n  s u bj ects  wit h  A V V C  bas e d  o n  p otassi u m 
h y dr o xi de ( K O H) testi n g at t he T O C visit  
•  T o e x pl ore t he efficac y of S C Y -0 7 8 i n s u bjects wit h A V V C base d o n a d diti o nal cli nical  
o utc o mes 
•  T o e x pl ore t he pre vale n ce of Ca n di da s pecies a m o n g s u bjects wit h A V V C 
•  T o e x pl ore t he i n vitr o acti vit y of S C Y- 0 7 8 a gai nst baseli ne Ca n di da s p p. is olates 
•  T o e x pl ore cli nical a n d m yc ol o gical o utc o mes b y Ca n di da s p ecies  
•  T o  e val uate  t he  P K  of  S C Y -0 7 8  after  oral  a d mi nistrati o n  of  differe nt  d ose  le vels  a n d 
d osi n g re gi me ns of S C Y- 0 7 8 i n s u bjects wit h A V V C 
3.  S T U D Y D E SI G N  
T his is a m ultice nter, ra n d o mize d, d o u ble -bli n d, d o u ble -d u m m y, acti ve -c o ntr olle d, d ose-fi n di n g 
st u d y  t o  c o m pare  t h e  efficac y,  saf et y  a n d  t olera bilit y  of  oral  S C Y-0 7 8  c o m pare d  t o  oral  


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fl uc o naz ole  i n  a d ult  fe male  s u bjects  1 8  years  a n d  ol der  wit h  m o derate  t o  se vere  A V V C. 
A p pr o xi matel y  1 8 0  eli gi ble  s u bjects  ( 3 0  s u bjects  per  treat me nt  gr o u p)  will  be  e nr olle d  a n d  
ra n d o mize d i nt o t he st u d y. 
T he  pri mar y  o bj ecti ve  of  t his  st u d y  is  t o  i de ntif y  t h e  rec o m me n de d  d os e  of  oral  S C Y -0 7 8  i n  
s u bjects wit h m o derat e t o se ver e A V V C b y c o m pari n g t he efficac y of differe nt d os e le v els a n d  
d osi n g re gi me ns of S C Y- 0 7 8. 
T he  st u d y  will  c o nsist  of  a  Scree ni n g  visit,  a  Baseli ne  vis it  o n  Da y  1,  a  st u d y  visit  o n  Da y  3 
( w hic h  will  c o nsist  of  a n  o n-site  visit  f or  P K  sa m pli n g  f or  a  s u bset  of  s u bjects  a n d  a  p h o ne 
c o ntact  f or all ot her s u bjects), a T O C visit ( w hic h will i ncl u de P K sa m pli n g f or t he P K S u bset of 
s u bjects) o n D a y 1 0 ( ± 2) a n d a F U visit o n D a y 2 5 ( + 4). T he Scree ni n g a n d Bas eli ne visits ma y 
be c o m bi ne d. Effi cac y, s afet y, t oler a bilit y a n d P K assess me nts will be c o n d ucte d f or t he st u d y. 
At  Scree ni n g,  s u bjects  w h o  are  e x perie n ci n g  v ul v o va gi nal  s y m pt o ms  will  be  e val uate d  b y  t h e  
i n vesti gat or, w h o will o btai n a va gi n al sa m ple f or l ocal K O H testi n g a n d f or f u n gal c ult ure a n d  
s pecies i de ntificati o n b y t he ce ntr al la b orat or y. S usce pti bilit y testi n g will be d o ne at t he ce ntral  
la b orat or y f or all p ositi ve c ult ures f or C a n di d a  s p p. A d diti o nal va gi nal sa m ples will be c ollecte d, 
if cli nicall y i n dicate d, t o be e x a mi ne d f or t he prese nce of ot her pat h o ge ns (e. g., ca usati ve a ge nts 
f or  bacterial  v a gi n osis, Tric h o m o n as , Her pes   vir us, N.  g o n orr he a , C hl a my di a ,  h u ma n 
pa pill o ma vir us or ot her mi x e d i nfecti o ns) b y a q ualifie d la b orat or y a n d f or t he deter mi nati o n of  
va gi n al  p H  b y  t he  i n vesti gat or.  T he  i n vesti gat ors  a n d  t he  s u bjects  will  rate  t he  si g ns  (e d e ma,  
er yt h e ma  a n d  e x c oriati o n)  a n d  s y m pt o ms  (itc hi n g,  b ur ni n g  a n d  irritati o n)  of  i nfecti o n,  
res pecti vel y, o n a sta n dar dize d v ul v o va gi nal si g ns a n d s y m pt o ms scale (t he V ul v o va gi n al Si g ns  
a n d  S y m pt o ms  [ V S S]  Scale).  Saf et y  pr o ce d ures,  i ncl u di n g  a n  a b bre vi ate d  p h ysical  e x a m,  vital  
si g ns, la b orat or y t ests a n d a pr e g na n c y test will als o be perf or me d. T o b e eli gi ble f or i ncl usi o n, 
s u bjects m ust ha ve a mi ni m u m c o m p osite sc ore of v ul v o va gi n al sig ns a n d s y m pt o ms ≥7 wit h at 
least 2 si g ns or s y m pt o ms ha vi n g a s c ore of 2 ( m o derate) or greater i n t he V S S Scale, a p ositi ve 
K O H test a n d a n or mal v a gi n al p H ( ≤4. 5).  
At t he Bas eli ne visit ( w hic h ma y b e c o m bi ne d wit h t he Scree ni n g visit), eli gi ble s u bjects  will be  
ra n d o mize d i n e q ual all o cati o n (at a 1: 1: 1: 1: 1: 1 rati o) t o o ne of t he f oll o wi n g 6 acti ve treat me nt 
gr o u ps ( 5 e x peri me ntal gr o u ps a n d 1 acti ve c o m parat or gr o u p): 
•  Treat me nt Gr o u p 1: oral S C Y- 0 7 8 7 5 0 m g Q D o n Da y 1 o nl y 
•  Treat me nt Gr o u p 2: oral S C Y- 0 7 8 3 0 0 m g BI D o n Da y 1 o nl y 
•  Treat me nt Gr o u p 3: oral S C Y- 0 7 8 4 5 0 m g BI D o n Da y 1 o nl y 
•  Treat me nt Gr o u p 4: oral S C Y- 0 7 8 1 5 0 m g BI D o n Da ys 1 t o 3 
•  Treat me nt Gr o u p 5: oral S C Y- 0 7 8 3 0 0 m g BI D o n Da ys 1 t o 3 
•  Treat me nt Gr o u p 6: oral fl uc o naz ole 1 5 0 m g Q D o n Da y 1 o nl y 
S u bjects  will  recei ve  r a n d o mize d  treat me nt  fr o m  Da y  1  t hr o u g h  D a y  3.  F or  t he  p ur p ose  of  
mai ntai ni n g treat me nt bli n di n g, all ra n d o mize d s u bjects will recei ve matc hi n g S C Y -0 7 8 place b o  


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ta blets a n d/ or matc hi n g fl uc o naz ole place b o ca ps ules as nee de d base d on treat me nt assi g n m e nt,  
i n  a  d o u ble-d u m m y  fas hi o n.  D uri n g  treat me nt  da ys,  s u bjects  will  rate  t heir  v ul v o va gi nal  
s y m pt o ms  a n d  rec or d  d osi n g  details,  A Es  a n d  c o nc o mita nt  me dicati o n  use  dail y  o n  s u bject  
diaries.  O n  Da y  3,  a  P K  S u bset  c o nsisti n g  of  1 0  s u bjects  per  treat me nt  gr o u p  (t otal  of  6 0 
s u bjects) will visit t he sit e t o ha v e P K sa m ples dra w n pre -d ose (i m me diat el y bef ore d osi n g) a n d 
at 2- 6 h o urs’ p ost -d ose of eit her t he m or ni n g or e ve ni n g d ose. D a y 3 will be a n o n -site visit f or 
P K  s u bjects  a n d  a  p h o ne  c o ntact  visit  ( wit h  a  wi n d o w  of  + 3  da ys)  f or  n o n -P K  s u bjects.  All 
s u bjects ( b ot h P K a n d n o n-P K s u bjects) will c o nti n ue t o ta ke t heir assi g n e d st u d y treat me nt a n d 
rate  t h eir s y m pt o ms  of  i nfecti o n  wit hi n  t heir  s u bject  diaries.  Treat me nt  c o m plia nce  will  be 
re vie we d  eit her  o n  site  or  b y  p h o ne  f or  all  s u bjects.  St u d y  dr u g  ma y  be  c ollect e d  fr o m  P K 
s u bjects w h o ha ve c o m plete d st u d y dr u g d osi n g at t he ti me of t his visit.  
At t he T O C visit ( Da y 1 0 [ ± 2]) va gi nal sa m ples will be o btai ne d f or l ocal K O H t esti n g a n d f or  
f u n gal  c ult ure  b y  t h e  ce ntral  la b orat or y.  I n  a d diti o n,  s usce pti bilit y  t esti n g  will  be  d o n e  at  t he 
ce ntral  la b orat or y  f or  all  p ositi ve  c ult ures  f or C a n di d a  s p p.  T he  i n vesti gat ors  a n d  t h e  s u bjects 
will  rate  t he  si g ns  a n d  s y m pt o ms  of  i nfecti o n,  res pecti vel y,  o n  t h e  V S S  Scale.  A n  a b bre viate d  
p h ysical e x a m, vital si g n meas ure me nts a n d s afet y la b orat or y tests will als o be perf or me d.  
A d diti o nall y, a si n gle P K sa m ple will be o btai ne d at a n y c o n v e nie nt ti me of t he da y fr o m t he P K  
S u bset  o nl y.  F or  t he  P K  S u bset,  t he  T O C  visit m ust  occ ur  as  cl ose  t o Da y  1 0  as  p ossi ble.  All  
s u bjects  will  ret ur n  t heir  s u bject  diaries.  C o m plia nce  wit h  st u d y  dr u g  d osi n g  will  be  e val uate d  
a n d st u d y dr u g will be c ollecte d f or all s u bjects w h o di d n ot ret ur n t heir st u d y dr u g o n Da y 3. 
At t he F U ( D a y 2 5[ + 4])) visit, va gi n al sa m ples will be o btai ne d f or l ocal K O H testi n g a n d f or  
f u n gal  c ult ure  b y  t h e  ce ntral  la b orat or y.  I n  a d diti o n,  s usce pti bilit y  t esti n g  will  be  d o n e  at  t he 
ce ntral  la b orat or y  f or  all  p ositi ve  c ult ures  f or C a n di d a  s p p.  T he  i n vesti gat ors  a n d  t h e  s u bjects 
will rate t h e si g ns a n d s y m pt o ms of i nfecti o n, res pecti vel y, o n t h e V S S Scale t o e val uate cli nical  
o utc o me. 
4.  H A R D W A R E A N D S O F T W A R E  
Statistical  a nal ysis  will  be  perf or me d  f oll o wi n g N o vella sta n d ar d  o p erati n g  pr oce d ures  a n d  o n 
t he N o vella c o m p uter net w or k. All statistical a n al ysis will be perf or me d usi n g S A S V ersi o n 9. 3 
wit h  pr o gra m  c o de  pre p are d  s p ecificall y  f or  t he  pr oject  b y  q ualifie d N o vella  statisticia ns  a n d 
S A S pr o gra m mers.  
T he  S A S  pr o gra ms  will  ge nerate  ric h -t e xt-f or matte d  ( R T F)  o utp ut  wit h  t he  “ R T F”  e xte nsi o n 
usi n g  t he  S A S  O ut p ut  Deli ver y  S yste m  ( O D S).  T he  s u m mar y  ta bles  a n d  listi n gs  will  be 
f or matte d  usi n g  t he  Ti mes  Ne w  R o ma n  9-p oi nt  f o nt.  T he  R T F  o ut p ut  is  i ncl u de d  i n  re p ort 
d oc u me nts  pre pare d  wit h  Micr os oft  W or d  a n d  c o n verte d  t o  P D F  f or mat  wit h o ut  t y p o gra p hical 
c ha n ge.  


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Data sets  will  be  create d  a n d  ta ke n  as  i n p ut  t o  vali date d  S A S  pr o gra ms  t o  ge nerate  t he  re p ort-
rea d y t a bles, listi n gs, a n d fi g ures. Eac h o ut p ut dis pla y will s h o w t he na m es of t he d ata s ets a n d 
S A S pr o gra m us e d t o pr o d uce it.  
5.  D A T A B A S E C L O S U R E  
After c o m pleti o n of all data r e vie w pr oce d ures, v ali dati o n of t he pr oject d ata base, a n d a p pr o val 
of t he data re vie w d oc u me nt b y t he st u d y  s p o ns or, t he cli nical data base  will be cl ose d  a n d t he 
st u d y will b e u n bli n de d. A n y c ha n ge t o t he cli nical data b ase after t his ti me will re q uire writte n 
a ut h orizati o n, wit h e x pla nati o n, b y t he S p o ns or a n d t he Bi ostatisticia n.    
6.  S A M P L E SI Z E D E T E R MI N A TI O N  
T his  is  a n  e x pl orat or y  st u d y  a n d  n o  f or m al  sa m ple  size  calc ulati o n  was  perf or me d.  
A p pr o xi matel y  1 8 0  s u bjects  will  be  e nr olle d  a n d  ra n d o miz e d  i n  a n  e q ual  all ocati o n  (at  a 
1: 1: 1: 1: 1: 1 rati o) t o t he si x st u d y tr eat me nt gr o u ps (see Ta bl e 1). T hirt y s u bjects per gr o u p are 
esti mate d t o be a d e q uate t o perf or m a n i nitial ass ess me nt of t he s afet y a n d t olera bilit y  as well as 
t he p ote ntial efficac y of S C Y- 0 7 8 i n s u bjects wit h A V V C. 
7.  A N A L Y SI S P O P U L A TI O N S  
T he f oll o wi n g a nal ysis sets/ p o p ulati o ns will be use d i n t his trial:  
•  I nte nt-t o-Tre at (I T T) p o p ul ati o n : All ra n d o mize d s u bjects 
•  M o difie d  I nte nt -t o-Tre at  ( mI T T)  P o p ul ati o n : All  ra n d o mize d  s u bjects  w h o  ha v e  a  
p ositi ve K O H test a n d a c o nfir me d p ositi ve m yc ol o gical c ult ure f or yeast at Baseli ne.  
•  Per  Pr ot o c ol  ( P P)  p o p ul ati o n : All  mI T T  s u bjects  w h o  ha ve  c o m plete d  t he  st u d y  dr u g 
treat me nt,  w h o  ha ve  a  T O C  e val uati o n  A N D  w h o  ha ve  n o  maj or  pr ot oc ol  de viati o ns 
(e. g.,  vi olati o n  of I n cl usi o n/ E x cl usi o n  criteria,  use  of  i nterferi n g  c o nc o mita nt 
me dicati o ns) . T he  T O C  e val uati o n  will  be  c o nsi dere d  a n  e val uati o n  wit hi n t he  Visit 4/ 
T O C/  Da y  1 0  a nal ysis  wi n d o w  a n d  ma y  i n cl u de u nsc he d ul e d  visits  fr o m  s u bjects  w h o 
atte n de d  t he  T O C  visit  late.  S u bjects  t o  be  i ncl u de d  i n  t he  P P  p o p ulati o n  will  be 
deter mi ne d  b y  t he  S p o ns or/ C R O  pri or  t o  t he  u n bli n di n g  of  t he  st u d y.  Pri or  t o  brea ki n g 
t he  bli n d,  a d diti o nal  criteria  f or  e x cl usi o n  fr o m  t he  P P  p o p ulati o n  ma y  be  i ncl u de d  t o 
acc o m m o date f or u nf ores ee n e v e nts t hat occ urre d d uri n g t he c o n d uct of t he st u d y. 
•  S af et y p o p ul ati o n : All ra n d o mize d s u bjects w h o recei v e d at least o ne d os e of st u d y dr u g 
a n d w h o ha ve at least o n e p ost- Bas eli ne e v al uati o n  
•  P h ar m a c o k i netic  ( P K)  p o p ul ati o n: All  ra n d o mize d  s u bjects  w h o  recei v e d  st u d y  dr u g 
a n d pr o vi de d at least o ne P K sa m ple. 


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T he m I T T  p o p ulati o n  will  be  t he  pri mar y  p o p ul ati o n  f or  effi cac y  a nal ysis.  T he I T T  a n d P P 
p o p ulati o n  will  be  sec o n dar y  f or  t he  pri mar y a n d  sec o n d ar y e n d p oi nts  o nl y.  T he  Safet y 
p o p ulati o n will be use d f or t he a nal yses of safet y e n d p oi nts. 
All  efficac y  a nal yses  will  be  c o n d ucte d  acc or di n g  t o  t he  ra n d o mize d  treat me nt  assi g n me nt;  all 
safet y a n al ys es will be c o n d ucte d acc or di n g t o t he treat me nt act u all y recei ve d. 
8.  H A N D LI N G O F MI S SI N G D A T A  
F or t he a n al ys es of efficac y e n d p oi nts , s u bjects w h o ha ve a missi n g val ue at t he T O C visit or F U 
visit  will be assi g ne d as treat me nt f ail ures , i.e., n o n-res p o n ders or p ositi ve m yc ol o gical o utc o me.   
T he ha n dli n g of b el o w le vel of q ua ntitati o n ( B L Q) val ues i n P K a nal ysis will be descri be d i n t he 
secti o n bel o w.  
N o ot her i m p utati o n will be use d u nless ot her wis e s pecifie d.  
9.  I N T E RI M A N A L Y SI S 
 N o i nteri m a nal ysis is pla n ne d f or t his st u d y. 
1 0.  D A T A C O N V E N TI O N S F O R A N A L Y SI S  
1 0. 1  
Ge ner al St atistic al Pri nci ples  
All  statistical  tests  will  be  perf or me d  at  t he  u n a dj uste d  0. 0 5  (t w o -si de d)  or  e q ui val e ntl y  0. 0 2 5 
( o ne-si de d) l e vel of si g nifica nce. T he st u d y is n ot p o were d f or f or mal statistical c o m paris o ns. 
All  o bser ve d  a n d  deri ve d  varia bles  (e. g.,  c ha n ge  fr o m  baseli ne,  res p o nse  stat us)  use d  i n  t he 
s u m maries of a nal ys es will be prese nte d i n b y-s u bject listi n gs. Descri pti ve statistics will be use d 
t o pr o vi de a n o v er vie w of t he effi cac y a n d safet y res ults. F or cate g orical p ara meters, t he n u m ber 
a n d per ce nta ge of s u bjects i n eac h cate g or y will be pres e nte d. T he d e n o mi nat or f or perce nt a ge 
will be base d o n t he n u m ber of s u bjects a p pr o priate f or t he p ur p ose of a nal ysis. F or c o nti n u o us 
para meters, descri pti ve statistics will i ncl u de n u m ber of s u bjects, 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.  
1 0. 2  
St u d y D a y  
Da y 1 is defi ne d as t he d ate of first st u d y dr u g a d mi nistrati o n. St u d y da y is calc ulate d relati ve t o 
t he date of D a y 1. 


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1 0. 3  
B aseli ne a n d C h a n ge fr o m B aseli ne  
Baseli ne is defi n e d as t he last n o n -missi n g assess me nt pri or t o t he date (a n d ti me if  a p pr o priate) 
of t he first d ose of st u d y dr u g. C ha n ge fr o m bas eli ne is defi ne d as: p ost -bas eli ne  val ue – baseli ne 
val ue.  
1 0. 4  
A n al ysis Visit Wi n d o w  
W here ver a p plica bl e, efficac y a n d safet y e n d p oi nts  at Visit 1/ Scree ni n g, Visit 2/ Baseli ne, Visit 
3/ Da y 3, a n d Visit 5/ F U/ Da y 2 5   will be a nal yz e d acc or di n g t o t heir n o mi nal visits  . Visit 4/ 
T O C/ Da y 1 0 will be a nal yz e d  acc or di n g t o t he a n al ysis wi n d o w of st u d y d a y 8 t o st u d y da y 1 3, 
i ncl usi ve. U nsc he d ule d visits  fr o m s u bjects w h o atte n de d t he T O C visit late will be i ncl u de d if 
wit hi n  t he  a nal ysis  wi n d o w.  T he  b o u n ds  ma y  be  re vise d  after  re vie wi n g bli n de d  data. If  m ore 
t ha n  o ne  e val uati o n  is  assi g ne d  t o  t his  wi n d o w,  t he  e val uati o n  cl ose d  t o  st u d y  d a y  1 0  will  be 
use d f or t he a nal ysis. If t he t w o visits are e q ui dista nt fr o m t he tar get da y, t he earlier visit will be 
use d.   U ns c he d ule d  visit  assess me nts  will  be  dis pla ye d  i n  b y -s u bj ect  listi n gs,  wit h o ut  bei n g 
i ncl u de d i n t he s u m maries. 
1 1.  S T A TI S TI C A L E V A L U A TI O N  
1 1. 1  
S u bject Dis p ositi o n  
T he  n u m ber  a n d  per ce nta ge  of  s u bjects  scree ne d,  ra n d o mize d,  i ncl u de d  i n  eac h  a nal ysis 
p o p ulati o n,  c o m pleti n g  t he  st u d y,  wit h dra wi n g  fr o m  t he  st u d y (t o get her wit h  t he  reas o ns  f or 
wit h dra wal)  will  be  s u m marize d  usi n g  fre q ue nci es  a n d  perce nta ges  b y  treat me nt  gr o u p.  A  b y -
s u bject  listi n g  will  be  prese nte d  f or  all  s u bject  e nr oll me nt  a nd  dis p ositi o n.  Scree n  fail ures  a n d 
s u bjects n ot ra n d o mize d will be prese nte d i n b y-s u bject listi n gs.  
T he n u m ber of da ys i n t he st u d y ( d ate of st u d y c o m pleti o n / disc o nti n uati o n mi n us date of Da y 1 
pl us 1) will be s u m marize d usi n g d escri pti ve statistics f or eac h treat me nt gr o u p.  
Ta b ulati o n b y st u d y site will be pr o vi de d. 
1 1. 2  
Pr ot oc ol De vi ati o n  
Pr ot oc ol  de viati o ns  will  be  l o g ge d  i nt o  t he I L 2 data base  a n d  dis pla ye d  i n  a  b y-s u bject listi n g. 
O ne e x ce pti o n t o t his is O ut of Wi n d o w ( O O W) Visit pr ot oc ol de viati o ns.  A re p ort fr o m D S G 
e Case Li n k  will  be  r u n  at  t he  e n d  of  t he  st u d y  t o  o btai n  a  listi n g  of  all  O O W  Visit  pr ot oc ol 
de viati o ns. 


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1 1. 3  
De m o gr a p hic a n d B aseli ne C h ar acteristics  
De m o gra p hi cs a n d baseli ne c har acteristics will be s u m marize d o verall a n d b y treat me nt f or t he 
I T T,  P P  a n d  Saf et y  p o p ulati o ns.  T he  f oll o wi n g  d e m o gra p hic  a n d  b as eli ne  vari a bles  will  be 
i ncl u de d: 
•  A ge ( years)  
•  Race  
•  Et h nicit y  
•  Wei g ht ( k g)  
•  Hei g ht ( c m)  
•  B o d y mass i n de x ( k g/ m 2 ) 
1 1. 4  
St u d y Me dic ati o n a n d Visit C o m pli a nce  
F or t he p ur p ose of bli n di n g, t he n u m ber a n d a p p eara nce of d osa g e u nits will be t he sa me acr oss 
all treat me nt gr o u ps, as f oll o ws:  
•  Da y 1: 5 ta blets f or t he m or ni n g d ose + 3 ta blets a n d 1 ca ps ule f or t he e ve ni n g d ose 
•  Da y 2 a n d D a y 3: 2 ta blets f or t he m or ni n g d os e + 2 ta blets f or t he e v e ni n g d ose 
T he f oll o wi n g p ara m eters of st u d y dr u g e x p os ure a n d c o m plia nce will be s u m marize d f or eac h 
treat me nt gr o u p: 
•  T otal  n u m ber  of  d oses  t a ke n,  cal c ulate d  as  6  mi n us  t otal  n u m ber  of  d o ses  misse d;  if  a 
s u bject’s  dr u g  acc o u nta bilit y  missi n g,  t he  s u bj ect’s  n u m ber  of  d oses  ta ke n  will  be 
ass u me d as missi n g  
•  T otal n u m ber of b ottles r et ur ne d 
•  T otal  n u m ber  of  ta blets/ca ps ules  ta ke n,  calc ulat e d  as  t otal  n u m ber  of  ta blets/ca ps ules 
dis pe nse d  mi n us   total  n u m ber  of  ta blets/ca ps ules  ret ur n e d;  t otal  n u m ber  of 
ta blets/ca ps ules = 1 7 ( 9 o n Da y 1 pl us 4 o n Da y 2 a n d Da y 3 eac h) 
•  S u bjects wit h a n y n o n- c o m plia nce iss ue base d o n i n vesti gat or’s re vie w of s u bject diar y 
1 1. 5  
Pri or a n d C o nc o mit a nt Me dic ati o ns  
Pri or  ( wit h i n  t he  pre vi o us  2 8  da ys a n d  wit h  st o p  dates  pri or  t o  first  d ose  of  st u d y  dr u g)  a n d 
c o nc o mita nt ( o n g oi n g or wit h st o p dates o n or aft er first d ose of st u d y dr u g) m e dicati o ns will be 
prese nte d  f or  t he  saf et y  p o p ulati o n  i n  a  b y -s u bject  listi n g  f or  eac h  treat me nt  gr o u p.  If  t he 
me dicati o n is o n g oi n g or t he st o p year is missi n g, t he me dicati o n will be c o nsi dere d as recei ve d 
f or t he e ntire d urati o n of t he st u d y. Me dicati o ns will be c o de d usi n g W H O- D D ter mi n ol o g y.  


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F or t he det er mi nati o n of pri or vs c o nc o mita nt me dicati o ns, t he f oll o wi n g r ules re gar di n g t he st o p 
date will be a p plie d:  
•  If  o nl y  year  was  r ec or d e d,  a n d  it  is  bef ore  Baseli ne,  it  is  a  pri or  me dicati o n;  if  year  is 
sa me or aft er Baseli ne, it is ass u me d t o be a c o nc o mita nt me dicati o n.  
•  If  da y  is  missi n g,  b ut m o nt h  a n d  year  are  bef ore  Baseli ne,  it  is  a  pri or  me dicati o n;  if 
m o nt h a n d year are t he s a me as Baseli ne, it is ass u me d t o be a c o nc o mita nt me dicati o n; if 
m o nt h a n d year are after Baseli ne, it is a c o n c o mita nt me dicati o n.  
•  If start date is after Bas eli ne, it is a c o nc o mita nt me dicati o n re gar dless.  
I n  a d diti o n,  pri or  a n d  c o nc o mita nt  me dicati o ns  will  be  s u m marize d  b y  treat me nt,  W H O-D D 
A nat o mical - T hera pe utic-C he mical ( A T C) classifi cati o n a n d preferre d ter m ( P T).  
1 1. 6  
Me dic al Hist or y
 a n d C o nc urre nt Pr oce d ures  
Me dic al  hist or y  (i ncl u di n g  pr e vi o us  a n d  o n g oi n g  me dical  c o n diti o ns)  will  be  c o de d  usi n g 
Me d D R A a n d pr ese nte d i n a b y- s u bj ect listi n g.  
1 1. 7  
P h ysic al E x a mi n ati o n  
A b n or mal  fi n di n gs  of  p h ysical  e x a mi nati o n at  Scree ni n g  a n d  T O C will   be pres e nte d  i n  a  b y -
s u bject listi n g.  
1 1. 8  
Effic ac y E n d p oi nts  
1 1. 8. 1  Pri m ar y Effic ac y E n d p oi nt  
T he pri mar y efficac y e n d p oi nt is t he perce nta ge of s u bjects wit h C li nical C ure  at t he T O C visit .  
C li nical C ure  is defi ne d as c o m plete res ol uti o n of si g ns a n d s y m pt o ms  of v ul v o va gi nal i nfecti o n 
wit h o ut nee d f o r f urt her a ntif u n gal treat me nt. S pecificall y , f or c o m plete res ol uti o n, a n y si g n or 
s y m pt o m s h o ul d be a bse nt (sc ore = 0) b y t h e T O C visit. If a n y si g n or s y m pt o m is missi n g, t he 
s u bject’s Cli nical C ure stat us will be c o nsi dere d as missi n g. 
C o n versel y, Cli ni cal  Fail ure is  defi ne d  as  no  res p o nse  t o  t hera p y  or  i nc o m plete  res ol uti o n  of 
si g ns  a n d  s y m pt o ms  or nee d  f or  a d diti o nal  v ul v o va gi n al  or  s yste mic  a ntif u n gal  t hera p y.  If  t he 
s u bject  recei v es  or  self-a d mi nisters  t o pical  dr u g  t hera p y  f or  t he  treat me nt  of  v ul v o va gi nal 
irritati o n/ pr urit us s uc h as t o pical a n al gesic or c ortic oster oi d aft er c o m pleti n g treat me nt wit h t he 
st u d y dr u g a n d b ef or e t he T O C visit, t he s u bject is c o nsi dere d a cli nical fail ure. 
T he  si g ns  ( e de ma,  er yt h e ma  a n d  e x c oriati o n  or  fiss ures)  a n d  s y m pt o ms  (itc hi n g,  b ur ni n g  a n d  
irritati o n) of i nfecti o n will be assesse d b y t he  i n vesti gat or  a n d  t he s u bject, res pecti vel y, o n t he 
V S S  Scale. T he V S S Scale is a sta n dar dize d, pre defi ne d scale w h ere eac h  si g n a n d s y m pt o m will 


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be gi ve n a n u merical rati n g b ase d o n se v erit y (a bs e nt = 0; mil d = 1; m o derate = 2; se v ere = 3) t o 
calc ulate a t otal c o m p osite sc ore.  
1 1. 8. 2  Sec o n d ar y Effic ac y E n d p oi nts  
T he sec o n d ar y  efficac y e n d p oi nts i ncl u de t he f oll o wi n g: 
•  T he perce nta ge of s u bjects wit h M yc ol o gi c al Era dicati o n ( ne gati ve f u n gal c ult ure) at t he 
T O C  a n d F U visit .  
M yc ol o gic al  Er a dicati o n is  defi ne d  as  a  s u bject  wit h  ne gati ve  c ult ure  ( n o  gr o wt h)  f or 
C a n di d a  s pecies.  C o n versel y, M yc ol o gic al  Persiste nce is  defi ne d  as  a  s u bject  wit h 
p ositi ve c ult ure f or C a n di d a  s pecies. 
•  T he  per ce nta ge  of  s u bj ects  wit h  b ot h C li nical C ure  a n d M yc ol o gic al  E ra dicati o n at  t he 
T O C visit.  If eit her c o m p o ne nt assess me nt is missi n g, t he s u bject will be c o nsi dere d as 
missi n g f or t his e n d p oi nt a n d i m p ute d as n o n-res p o n ders i n t he a nal ysis 
•  T he  perce nta ge  of  s u bjects  wit h  b ot h  a bse nce  of  si g ns  a n d  s y m pt o ms   a n d  Myc ol o gic al 
E ra dicati o n at t he F U visit . If eit her c o m p o n e nt assess me nt is missi n g, t he s u bject will be 
c o nsi dere d as missi n g f or t his e n d p oi nt a n d i m p ute d as n o n-res p o n d ers i n t he a nal ysis 
•  T he perce nta ge of s u b jects wit h C o nti n ue d C li nical Re s p o nse at t he F oll o w-u p ( F U) visit, 
defi ne d as c o nti n ue d a bs e nce of si g ns a n d s y m pt o ms  i n s u bjects w h o ac hie ve d Cli nical 
C ure at t he T O C visit  
•  T he  ti me  t o  r es ol uti o n  of  si g ns  a n d  s y m pt o ms  after  i nitiati o n  of  st u d y  dr u g ,  d efi ne d  as 
ti me  ( da ys)  fr o m  first  d ose  of  st u d y  me di cati o n  t o  t he  first  res ol uti o n  of  si g ns  a n d 
s y m pt o ms.  S u bjects  w h o  disc o nti n ue d  earl y  will  be  ce ns ore d  at  t he  last  a vaila ble 
assess me nt.  
1 1. 8. 3  E x pl or at or y Effic ac y E n d p oi nts  
T he e x pl orat or y effi cac y e n d p oi nt s i ncl ude t he f oll o wi n g: 
•  Perce nta ge of s u bjects wit h a ne gati ve K O H test at t he T O C visit  
•  Perce nta ge of s u bjects w h o are free of si g ns a n d s y m pt o ms at t he F U visit 
•  Perce nta ge of s u bjects b y C a n di d a  s pecies i nfecti o n at Bas eli ne 
•  Perce nta ge of is olates s usce pti ble t o S C Y- 0 7 8 a n d fl uc o naz ole at t he T O C a n d F U visits  
•  Perce nta ge of s u bjects wit h cli nical c ure at T O C b y C a n di d a  s pecies at Baseli ne  
•  Perce nta ge  of  s u bjects  wit h  m yc ol o gical  era di cati o n  at  T O C  b y  C a n di d a  s pecies at 
Baseli ne  


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1 1. 9  
Effic ac y A n al yses  
1 1. 9. 1  Pri m ar y Effic a c y A n al ysis 
T he pri mar y efficac y a n al ysis will be c o n d ucte d usi n g t he  mI T T  ( pri mar y a nal ysis p o p ulati o n), 
I T T a n d P P p o p ulati o ns.  
T he pri mar y e n d p oi nt ( cli nical c ur e at T O C) will be a nal yze d usi n g a C oc hra n -Ma ntel -Hae nszel 
r o w  mea n  sc or es  test stratifie d b y  site.  Pair wise  treat me nt  c o m paris o ns  of  S C Y -0 7 8  vs.  acti ve 
c o m parat or (fl uc o n az ole) will  be  perf or me d  usi n g  a  Fis her ’s  E x act  test;  p-val ues  a n d  9 5 % 
c o nfi de nce i nter vals f or o d ds rati o will be prese nte d. S u bjects w h ose res ults are missi n g at Da y 
1 0  ( T O C)  will  be  i m p ute d  as  fail ures  i n  t he  a n al ysis.  A  se nsiti vit y  a nal ysis  will  be  perf or me d 
w here s u bjects  wit h missi n g val ues will be re m o v e d fr o m t he a n al ysis.  
V S S  sc ores  at  Baseli ne,  T O C,  a n d  F U  will  be  s u m marize d  f or  eac h  si g n  a n d  s y m pt o m  usi n g 
fre q ue n c y  c ou nts  a n d  p erce nt a ges.  S u m mar y  statistics  will  be  pr o vi de d  f or  t he  t otal  V S S 
c o m p osite  sc ore  ( o bser v e d  val ue  a n d  c h a n ge  fr o m  baseli ne).  St u de nt’s  t -test  will  be  use d  f or 
pair wise  tr eat me nt  c o m paris o ns  of  S C Y -0 7 8  vs.  fl uc o naz ole;  p -v al ues  a n d  9 5 %  c o nfi de nce 
i nter vals will be prese nt e d f or t he diff ere n ces bet wee n treat me nt gr o u ps.  
1 1. 9. 2  Sec o n d ar y Effic ac y A n al yses  
T he sec o n d ar y  efficac y a nal ys es will be c o n d ucte d usi n g t he mI T T, I T T a n d P P p o p ulati o ns. 
Bi nar y efficac y e n d p oi nts  ( m yc ol o gical era dicati o n,  c o m p osite  cli nical  c ure  a n d  m yc ol o gical 
era diati o n, a n d c o nti n ue d cli nical res p o nse at F U) will be a nal yze d usi n g t h e sa me met h o d s/tests 
as descri be d f or t he pri mar y efficac y e n d p oi nt. 
Ti me t o  r es ol uti o n of si g ns a n d s y m pt o ms after i nitiati o n of st u d y dr u g will be a n al yze d usi n g 
Ka pla n -Mei er  met h o ds.  Pair wise  treat me nt  c o m paris o ns  of  S C Y -0 7 8  vs.   fl uc o naz ole will  be 
perf o r me d usi n g l o g-ra n k test. 
1 1. 9. 3  E x pl or at or y Effic ac y A n al yses  
T he e x pl orat or y efficac y  a nal ys es  will  be  c o n d ucte d  usi n g  t he mI T T  a n d  P P p o p ulati o ns , 
f oll o wi ng t he sa m e met h o ds /tests as descri be d f or t he pri mar y a n d sec o n dar y e n d p oi nts.  
F or  t he  s u b gr o u p  a nal ys es  b y  C a n di d a  s pecies,  o nl y  d escri pti ve  statistics  will  be  pr o vi de d;  n o 
statistical testi n g will be perf or me d d u e t o p ossi ble s mall sa m ple size. 
1 1. 1 0  
S afet y A n al ysis  
Safet y s u m maries will be perf or me d o n t he Safet y p o p ulati o n. 


S C Y N E XI S, I nc.  
                            Pa ge 1 5 of 1 7 
Pr ot oc ol N o. S C Y - 0 7 8- 2 0 4 
J u ne 5, 2 0 1 8   
 
S A P versi o n 1 . 0 
1 1. 1 0. 1  A d verse E ve nts  
A E ter ms will be c o de d usi n g Me d D R A dicti o nar y. A treat me nt -e m er ge nt A E ( T E A E) is defi ne d 
as  a n  A E  t hat  starts  or  w orse n  o n  or  after  t he  date  of  t he  first  d ose  of  st u d y  me d icati o n.  If 
relati o ns hi p t o treat me nt is missi n g, t he e ve nt will be c o nser vati vel y c o nsi dere d as bei n g relate d 
t o st u d y dr u g. If s e verit y is missi n g, a se parate cate g or y of missi n g s e verit y will be i ncl u de d i n 
t he s u m mar y ta ble, a n d n o i m p utati o n of se verit y will be perf or me d. T hr o u g h t he data clea ni n g 
pr ocess, all atte m pts will be ma de t o a v oi d missi n g val ues f or relati o ns hi p a n d se verit y.  
All A Es will be prese nte d i n a b y -treat me nt a n d b y-s u bject listi n g, detaili n g t he ver b ati m ter m 
gi ve n  b y  t he  i n vesti g at or,  t he  pref err e d  ter m  ( P T),  s yste m  or ga n  class  ( S O C),  o nset  date,  e n d 
date,  se verit y,  o ut c o me,  relati o ns hi p  t o  st u d y  dr u g,  acti o n  ta ke n  wit h  st u d y  dr u g,  ot her  acti o n 
ta ke n, seri o us ness a n d criteria f or seri o us ness. Seri o us A Es ( S A Es) a n d T E A Es lea di n g t o st u d y 
disc o nti n uati o n will als o be prese nt e d i n a se parat e listi n g.  
A n  o verall  s u m mar y  of  A Es  will  be  pres e nte d  b y  treat me nt  a n d  o v erall.  T he  s u m mar y  will 
i ncl u de t he t otal n u m ber of e ve nts, fr e q ue n c y c o u nts a n d perce nta ges wit h: 
•  
A n y A E  
•  
A n y T E A E  
•  
A n y s eri o us T E A E  
•  
A n y treat me nt -relate d T E A E, i ncl u di n g defi nitel y r elate d, pr o ba bl y relate d, a n d p ossi bl y 
relate d  
•  
A n y T E A E lea di n g t o st u d y dr u g disc o nti n uati o n  
S u m maries of t he i nci de nce of T E A Es will be dis pla ye d b y treat me nt acc or di n g t o t he f oll o wi n g:  
•  
All T E A Es b y S O C i n al p ha betical or der a n d P T i n desce n di n g or der of fre q ue nc y (t he 
c o m bi ne d fre q ue nc y i n t he t w o acti ve treat me nts)  
•  
All T E A Es b y S O C, P T, a n d ma xi m u m se verit y ( mil d, m o derate, or se vere)  
•  
All T E A Es b y S O C, P T, a n d ma xi m u m ca usalit y ( n ot relate d, relate d) t o t he st u d y dr u g  
At eac h le vel of s u m marizati o n, a s u bject will  be c o u nte d o nce if he/s he re p orte d o ne or m ore 
e ve nts.  T he  se verit y  of  T E A Es  a n d  relati o ns hi p  t o  st u d y  dr u g  will  be  s u m marize d  i n  a  si milar 
ma n ner. F or s u m maries of rel ati o ns hi p t o st u d y dr u g, a s u bj ect will be classifie d acc or di n g t o t he 
cl osest relati o ns hi p. F or s u m maries of T E A E se verit y, a s u bject will be classifie d acc or di n g t o 
t he hi g hest se v erit y. 
1 1. 1 0. 2  Cli nic al L a b or at or y Testi n g  
A bs ol ute val ues a n d c ha n ges fr o m bas eli ne wil l be s u m marize d f or cli nical la b orat or y (c he mistr y 
a n d he mat ol o g y) res ults usi n g descri pti ve statistics. S hift ta bles f or eac h cli nical la b orat or y test 
will  cr oss -ta b ulate  t he  n u m ber  of  s u bjects  wit h  val ues  bel o w  t he  la b orat or y  refere n ce  ra n ge 
(l o w), val ues wit hi n t he la b orat or y r efere nce ra n ge ( n or mal) or a b o v e t he l a b orat or y ra n ge ( hi g h) 


S C Y N E XI S, I nc.  
                            Pa ge 1 6 of 1 7 
Pr ot oc ol N o. S C Y - 0 7 8- 2 0 4 
J u ne 5, 2 0 1 8   
 
S A P versi o n 1 . 0 
at  baseli ne  wit h  t he  n u m ber  of  s u bjects  wit h  l o w,  n or mal  or  hi g h  v al ues  at  eac h  p ost -bas eli ne 
ti me p oi nt. N or mal ra n ges a n d val ues o utsi de t he n or mal ra n ges will be i de ntifie d b y t h e ce ntral 
la b orat or y. A s e par ate listi n g of o ut of n or mal ra n ge l a b orat or y res ults will be pr o vi de d.  
Uri ne  pre g n a nc y test will be prese nt e d wit h s u bject c hil d beari n g p ote ntial i n a b y-s u bject listi n g.  
1 1. 1 0. 3  Vit al Si g ns  
Vital si g ns i ncl u di n g bl o o d pr ess ure  (s yst olic a n d diast olic), heart rate, res pirat or y rate a n d b o d y 
te m perat ur e will be pr es e nte d i n a b y -s u bject listi n g b y visit. A bs ol ute val ues a n d c h a n ge fr o m 
baseli ne val ue will be s u m marize d b y treat me nt gr o u p usi n g des cri pti ve statistics.  
1 1. 1 1  
P h ar m a c o ki netics 
F or s u bjects t hat c o nse nt t o pr o vi di n g P K sa m ples , bl o o d will be dra w n at t he Da y 3 a n d T O C 
( Da y 1 0) visits. O n Da y 3, sa m ples will be c ollecte d pre-d ose (i m me diatel y bef ore d osi n g) a n d at 
2- 6 h o urs p ost -d ose of eit her t he m or ni n g or e v e ni n g d os e ( 5t h or 6 t h d ose of st u d y dr u g) . O n Da y 
1 0,  a  si n gle  P K  sa m pl e  will  be  c ollecte d  at  a n y  ti me. F or  t he  P K  S u bset,  t he  T O C  visit  m ust 
occ ur as cl ose t o Da y 1 0 as p ossi ble. 
T he a nal yses of P K c o nce ntrati o ns a n d P K para meters will be descri be d i n a se parate re p ort. T he 
re p ort will be pre p ar e d b y a v e n d or sel ecte d b y Sc y n e xis after d ata bas e l oc k. 
1 2.  C H A N G E S F R O M T H E P R O T O C O L A N D P L A N N E D A N A L Y S E S  
T his  S A P  reflects  t he  a nal ysis  pla n  o utli ne d  i n  t he  st u d y  pr ot o c ol  wit h o ut  si g nifica nt  c ha n ge. 
A n y  a nal ysis  c ha n ges  or a d diti o nal  a n al ysis  n ot  s pecifie d  i n  t his  S A P  will  ha ve  t he  stat us  of 
u n bli n de d a n d e x pl orat or y i n vesti gati o ns. 
1 3.  H E A DI N G S  
Eac h  pa ge  of  t h e  a n al ysis  will  s h o w  t he  s p o ns or’s  na me,  t h e  i n vesti gati o nal  pr o d uct,  a n d  t he 
pr ot oc ol n u m ber. Re p ort ta bles will be e m be d de d i n  t he  M S W or d re p ort d oc u me nt fr o m S A S 
pr o gra m o ut p ut wit h o ut c ha n ge. T h e f o oter of eac h ta ble will s h o w t he n a me of t he S A S pr o gra m 
m o d ule w hic h ge nerate d it, t he na mes of all data s ets pr o vi di n g i n p ut data i n t he pr o gra m a n d t he 
date a n d ti me t he ta ble w as ge ner ate d.  
1 4.  A R C HI VI N G A N D R E T E N TI O N O F D O C U M E N T S  
After fi nalizati o n of t he a nal ysis, t h e f oll o wi n g will be arc hi ve d at N o vella Cli nical  a n d/ or wit h 
t he st u d y s p o ns or: 
•  S A P a n d a n y a me n d me nts  


S C Y N E XI S, I nc.  
                            Pa ge 1 7 of 1 7 
Pr ot oc ol N o. S C Y - 0 7 8- 2 0 4 
J u ne 5, 2 0 1 8   
 
S A P versi o n 1 . 0 
•  All  S A S  c o de  use d  i n  t he  pr oject  f or  statistical  a nal ysis ,  re p ort  ta bl es  ge n erati o n,  a n d 
a nal ysis d ata set creati o n  
•  Ta bles, listi n gs a n d fi g ur es as i ncl u de d i n t he cli ni cal st u d y re p ort 
•  S A S st u d y d ata ta b ulati o n m o del ( S D T M) a n d a n al ysis datas et m o del ( A D a M) datasets  
1 5.  O U T LI N E O F P R O P O S E D T A B L E S, LI S TI N G S A N D FI G U R E S 

Prot_001.pdf: 
 
SCYNEXIS, Inc. 
Clinical Trial Protocol 
A Phase 2, Multicenter, Randomized, Double-Blind, Double-Dummy, 
Active-Controlled, Dose-Finding Study to Compare the Safety and Efficacy 
of Oral SCY-078 vs. Oral Fluconazole in Subjects with Acute Vulvovaginal 
Candidiasis (DOVE) 
SCYNEXIS Protocol Number SCY-078-204 
 
SCYNEXIS, Inc. 
101 Hudson Street, Suite 3610 
Jersey City, NJ 07302 
 
Original Protocol Issue Date: 08 June 2017 (Version 1.0) 
Protocol Amendment 1 Issue Date: 13 Jul 2017 (Version 2.0) 
 
US IND Number 107,521 
STATEMENT OF CONFIDENTIALITY 
The information in this document contains trade secrets and commercial information 
that are privileged or confidential and may not be disclosed unless such disclosure is 
required by federal or state law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or 
confidential and may not be further disclosed by them. These restrictions on disclosure 
will apply equally to all future information supplied to you which is indicated as 
privileged or confidential. 
NCT03253094


SCYNEXIS, Inc. 
IND #107,521 
PROTOCOL SCY-078-204 
Version 2.0 
 
13 JUL 2017 
CONFIDENTIAL 
 
Page 2 
 
1.0 Contact Information 
 
   Contract Research Organization 
 
 
 
Study Medical Monitor 
 
 
 
Clinical Project Manager 
 
 
 
Sponsor 
SCYNEXIS, Inc. 
101 Hudson Street, Suite 3610 
Jersey City, NJ 07302  
Phone: +1.201.884.5485 
Fax: +1.201.884.5490 
Email: info@scynexis.com 
 
 
 




SCYNEXIS, Inc. 
IND #107,521 
PROTOCOL SCY-078-204 
Version 2.0 
 
13 JUL 2017 
CONFIDENTIAL 
 
Page 4 
 
Investigator Agreement Statement 
PROTOCOL ID: SCY-078-204 
A Phase 2, Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled, 
Dose-Finding Study to Compare the Safety and Efficacy of Oral SCY-078 vs. Oral 
Fluconazole in Subjects with Acute Vulvovaginal Candidiasis (DOVE) 
 
I understand that all documentation provided to me by SCYNEXIS, Inc. or its designated 
representative(s) concerning this study that has not been published previously will be kept 
in the strictest confidence. This documentation includes the study protocol, Investigator’s 
Brochure, case report forms, and other scientific data. This study will not commence 
without the prior written approval of a properly constituted Institutional Review Board or 
Ethics Committee. No changes will be made to the study protocol without the prior written 
approval of SCYNEXIS, Inc. and the Institutional Review Board/Ethics Committee, except 
where necessary to eliminate an immediate hazard to the patient. All patients will provide 
a written informed consent prior to participation. 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I have read, understood and 
agree to abide by all the conditions and instructions contained in this protocol, and in 
compliance with International Conference on Harmonization (ICH) guidelines, Good 
Clinical Practices (GCP), Safety Reporting obligations and any applicable local 
requirements. 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
Principal Investigator’s Name (Printed) 
 
 
 
 


SCYNEXIS, Inc. 
IND #107,521 
PROTOCOL SCY-078-204 
Version 2.0 
 
13 JUL 2017 
CONFIDENTIAL 
 
Page 5 
 
TABLE OF CONTENTS 
1.0 
Contact Information ................................................................................................ 2 
2.0 
Protocol Approvals ................................................................................................. 3 
3.0 
Revision History ................................................................................................... 10 
4.0 
Abbreviations ........................................................................................................ 11 
5.0 
Protocol Synopsis.................................................................................................. 13 
6.0 
Schematic of Study Design ................................................................................... 22 
7.0 
Background Information and Scientific Rationale ............................................... 23 
7.1 
Background Information ............................................................................... 23 
7.2 
Rationale for the Study ................................................................................. 26 
8.0 
Study Objectives ................................................................................................... 28 
8.1 
Primary Objectives........................................................................................ 28 
8.2 
Secondary Objectives.................................................................................... 28 
8.3 
Exploratory Objectives ................................................................................. 28 
9.0 
Study Endpoints .................................................................................................... 28 
9.1 
Primary Endpoints ........................................................................................ 28 
9.2 
Secondary Endpoints .................................................................................... 28 
9.3 
Exploratory Endpoints .................................................................................. 29 
10.0 
Study Design ......................................................................................................... 29 
10.1 
Overall Description of the Study .................................................................. 29 
10.1.1 
Study Visits ............................................................................................... 30 
10.1.2 
Study Assessments .................................................................................... 32 
10.2 
Blinding, Randomization and Stratification ................................................. 33 
10.3 
Study Duration .............................................................................................. 33 
10.4 
Number of Centers ........................................................................................ 34 
11.0 
Study Population ................................................................................................... 34 
11.1 
Inclusion Criteria .......................................................................................... 34 
11.2 
Exclusion Criteria ......................................................................................... 35 


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11.3 
Discontinuation Criteria ................................................................................ 36 
11.4 
Replacement of Dropouts ............................................................................. 37 
12.0 
Study Treatments .................................................................................................. 37 
12.1 
Study Treatment Groups ............................................................................... 38 
12.2 
Dietary Requirements ................................................................................... 39 
12.3 
Study Drugs .................................................................................................. 39 
12.3.1 
SCY-078 Description ................................................................................ 39 
12.3.2 
Formulation, Packaging and Labelling ..................................................... 40 
12.3.3 
Storage and Stability ................................................................................. 41 
12.4 
Drug Accountability...................................................................................... 41 
12.5 
Subject Compliance with Study Drug Dosing .............................................. 42 
13.0 
Non-Study Treatments .......................................................................................... 42 
13.1 
Prior and Concomitant Medications ............................................................. 42 
13.2 
Prohibited Medications ................................................................................. 43 
13.3 
Medications to be Administered with Caution and Monitored as Appropriate
 
43 
13.4 
Study Restrictions ......................................................................................... 43 
14.0 
Study Procedures .................................................................................................. 44 
14.1 
Informed Consent.......................................................................................... 44 
14.2 
Assignment of Subject Number .................................................................... 44 
14.3 
Inclusion and Exclusion Criteria ................................................................... 44 
14.4 
Medical History and Demographics ............................................................. 44 
14.5 
Abbreviated Physical Examination ............................................................... 45 
14.6 
Urine Pregnancy Test .................................................................................... 45 
14.7 
Safety Laboratory Tests ................................................................................ 45 
14.8 
Vulvovaginal Samples for Identification of Other Pathogens and Vaginal pH
 
45 
14.9 
Vulvovaginal Samples for KOH and Fungal Culture ................................... 46 
14.10 
Rating of Vulvovaginal Signs by the Investigator Using the VSS Scale ..... 46 


SCYNEXIS, Inc. 
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PROTOCOL SCY-078-204 
Version 2.0 
 
13 JUL 2017 
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14.11 
Rating of Vulvovaginal Symptoms by the Subject Using the VSS Scale .... 46 
14.12 
Randomization .............................................................................................. 47 
14.13 
Study Drug and Subject Diary Dispensing ................................................... 47 
14.14 
Study Drug Dosing ....................................................................................... 47 
14.15 
Subject Diary Completion............................................................................. 47 
14.16 
Treatment Compliance Evaluation and Study Drug Collection  .................. 48 
14.17 
Subject Diary Collection and Review ........................................................... 48 
14.18 
Pharmacokinetic Sample Collection ............................................................. 48 
14.19 
Vital Signs ..................................................................................................... 48 
14.20 
Prior and Concomitant Medication Review .................................................. 48 
14.21 
Adverse Event Monitoring ............................................................................ 49 
15.0 
Study Schedule...................................................................................................... 50 
16.0 
Safety Assessments and Monitoring ..................................................................... 52 
16.1 
Definition of an Adverse Event .................................................................... 52 
16.2 
Definition of a Serious Adverse Event ......................................................... 53 
16.3 
Events of Clinical Interest ............................................................................. 53 
16.4 
Overdose ....................................................................................................... 54 
16.5 
Pregnancy ...................................................................................................... 54 
16.6 
Unexpected Adverse Event ........................................................................... 54 
16.7 
Grading of Adverse Events ........................................................................... 55 
16.8 
Causality Assessment.................................................................................... 55 
16.9 
Adverse Event Collection Timeframe .......................................................... 55 
16.10 
Serious Adverse Event Reporting Requirements .......................................... 56 
16.11 
Adverse Event and Serious Adverse Event Follow-up ................................. 56 
16.12 
Serious Adverse Event Reporting – Procedures for Investigators ................ 56 
16.13 
Procedures for Emergency Unblinding ......................................................... 57 
17.0 
Data Collection, Study Monitoring and Record Management.............................. 57 
17.1 
Data Collection and Reporting...................................................................... 57 
17.2 
Study Monitoring .......................................................................................... 57 


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IND #107,521 
PROTOCOL SCY-078-204 
Version 2.0 
 
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17.3 
Investigator Study Files ................................................................................ 58 
17.4 
Retention of Records..................................................................................... 58 
18.0 
Analytical Plan ...................................................................................................... 59 
18.1 
Sample Size Determination........................................................................... 59 
18.2 
Analysis Populations ..................................................................................... 59 
18.3 
Subject Disposition, Discontinuation, and Baseline Data ............................ 60 
18.4 
Handling of Missing Data, Dose Adjustments, and Early Withdrawals....... 60 
18.5 
Prior and Concomitant Medications ............................................................. 60 
18.6 
Pharmacokinetics .......................................................................................... 61 
18.6.1 
Pharmacokinetic Assessments .................................................................. 61 
18.6.2 
Pharmacokinetic Analyses ........................................................................ 61 
18.7 
Efficacy ......................................................................................................... 61 
18.7.1 
Efficacy Assessments................................................................................ 61 
18.7.2 
Efficacy Analyses ..................................................................................... 62 
18.8 
Safety ............................................................................................................ 63 
18.8.1 
Safety Assessments ................................................................................... 63 
18.8.2 
Analyses .................................................................................................... 63 
19.0 
Ethics and Protection of Human Patients.............................................................. 64 
19.1 
Ethical Conduct of the Study ........................................................................ 64 
19.2 
Institutional Review Board/Ethics Committee Review ................................ 64 
19.3 
Informed Consent.......................................................................................... 64 
19.4 
Future Use of Samples .................................................................................. 64 
19.5 
Subject Privacy and Subject Confidentiality ................................................ 65 
19.6 
Study Termination ........................................................................................ 65 
19.7 
Financial Disclosure...................................................................................... 65 
20.0 
References ............................................................................................................. 66 
21.0 
Appendices ............................................................................................................ 67 
Appendix A:  Prohibited Medications and Medications to be Administered with Caution
 
67 


SCYNEXIS, Inc. 
IND #107,521 
PROTOCOL SCY-078-204 
Version 2.0 
 
13 JUL 2017 
CONFIDENTIAL 
 
Page 9 
 
Prohibited Medications ............................................................................................. 67 
Medications to be administered with Caution and Monitored as Appropriate ......... 68 
Appendix B:  Vulvovaginal Signs and Symptoms Scale .............................................. 70 
 
LIST OF FIGURES 
Figure 1 
Schematic of Study Design ........................................................................... 22 
Figure 2 
Chemical Structure of SCY-078 Citrate ....................................................... 40 
LIST OF TABLES 
Table 1: 
Study Treatment Groups (Study SCY-078-204)........................................... 37 
Table 2: 
Schedule of Visits and Procedures (Study SCY-078-204) ........................... 50 
 
 
 
 


SCYNEXIS, Inc. 
IND #107,521 
PROTOCOL SCY-078-204 
Version 2.0 
 
13 JUL 2017 
CONFIDENTIAL 
 
Page 10 
 
3.0 Revision History 
Revisions to Protocol dated 08 Jun 2017 (Protocol Version 1.0) 
Current Version and Date: Protocol Amendment 1 (Protocol Version 2.0) dated 
13 Jul 2017 
Protocol Sections 
Change and Rationale 
Section 10.1.1 (Study 
Visits) and 
Section 15.0 (Study 
Schedule) 
Removed the option for a phone call for the FU visit to ensure 
collection of vaginal samples from all subjects for 
mycological assessment in order to accommodate the 
requirements of the secondary objective “percentage of 
subjects with both clinical cure and mycological eradication 
at the TOC and FU visits”. 
Section 14.9 (Vulvovaginal 
Samples for KOH and 
Fungal Culture), 
Section 15.0 (Study 
Schedule) and  
other applicable sections 
Added the collection of vaginal samples for KOH testing and 
fungal culture at FU for all subjects to assess treatment 
outcome, as required by the above mentioned secondary 
objective. 
Section 14.10 (Rating of 
Vulvovaginal Signs by the 
Investigator Using the VSS 
Scale) and 
other applicable sections 
Added the rating of signs of infection by the investigator in 
addition to the subject´s rating of symptoms for all subjects at 
FU, as a result of the fact that all FU visits will be conducted 
face to face. 
Section 7.2 (Rationale for 
the Study), 
Secondary and Exploratory 
Endpoints (Section 9.2 & 
Section 9.3), 
Section 10.1 (Overall 
Description of the Study 
including Section 10.1.1 & 
10.1.2) and  
Section 18.7.1 (Efficacy 
Assessments) 
Revised secondary and exploratory endpoints to include the 
assessment of both signs and symptoms at the FU visit, as a 
result of the fact that all FU visits will be conducted in 
person. 
Revised applicable outcome definitions to include signs of 
vulvovaginal infection.  
Section 11.1 (Inclusion 
Criteria) 
Clarified acceptable methods of contraception.  
Section 13 (Discontinuation 
Criteria) 
Clarified that all FU visit procedures should be done for 
subjects who discontinue after the TOC visit but before the 
FU visit. 


SCYNEXIS, Inc. 
IND #107,521 
PROTOCOL SCY-078-204 
Version 2.0 
 
13 JUL 2017 
CONFIDENTIAL 
 
Page 11 
 
Revisions to Protocol dated 08 Jun 2017 (Protocol Version 1.0) 
Current Version and Date: Protocol Amendment 1 (Protocol Version 2.0) dated 
13 Jul 2017 
Protocol Sections 
Change and Rationale 
Section 14.6 (Urine 
Pregnancy Test) 
Clarified that pregnancy test results will be reviewed at 
Baseline (Day 1) before starting/dispensing study drug. 
Section 14.7 (Safety 
Laboratory Tests) 
Removed segmented neutrophils from the list of parameters 
included in the differential WBC count. 
4.0 Abbreviations 
ABBREVIATION 
DEFINITION 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC0-24 
area under the concentration-time curve from 0 to 24 hours 
AVVC 
acute vulvovaginal candidiasis 
BID 
twice daily 
CD 
compact disk 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
Cmax 
maximum concentration 
CPK 
creatine phosphokinase 
CRO 
contract research organization 
CYP 
cytochrome P450 
DVD 
digital versatile disk 
EC 
Ethics Committee 
ECI 
event of clinical interest 
eCRF 
electronic case report form 


SCYNEXIS, Inc. 
IND #107,521 
PROTOCOL SCY-078-204 
Version 2.0 
 
13 JUL 2017 
CONFIDENTIAL 
 
Page 12 
 
ABBREVIATION 
DEFINITION 
FDA 
Food and Drug Administration 
FU 
follow-up 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyl transferase 
GSI 
glucan synthesis inhibitor 
IB 
Investigator´s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ID 
identification 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
ITT 
intent-to-treat 
IV 
intravenous 
IWRS 
interactive web response system 
KOH 
potassium hydroxide 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent to treat 
OATP1B3 
Organic anion-transporting polypeptide 1B3 
PI 
principal investigator 
PK 
pharmacokinetics 
Pop PK 
population pharmacokinetics 
PP 
per protocol 
QD 
once daily 
RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SGOT 
serum glutamic oxaloacetic transaminase 


SCYNEXIS, Inc. 
IND #107,521 
PROTOCOL SCY-078-204 
Version 2.0 
 
13 JUL 2017 
CONFIDENTIAL 
 
Page 13 
 
ABBREVIATION 
DEFINITION 
SGPT 
serum glutamic pyruvic transaminase 
SOC 
standard of care 
TOC 
test of cure 
ULN 
upper limit of normal 
US 
United States 
VSS Scale 
Vulvovaginal Signs and Symptoms Scale 
WBC 
white blood cell 
 
5.0 Protocol Synopsis 
Title: A Phase 2, Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled, 
Dose-Finding Study to Compare the Safety and Efficacy of Oral SCY-078 vs. Oral Fluconazole 
in Subjects with Acute Vulvovaginal Candidiasis (DOVE) 
Primary Objectives: 
• 
To identify the recommended dose of oral SCY-078 in subjects with moderate to severe 
acute vulvovaginal candidiasis (AVVC) by comparing the efficacy of different dose levels 
and dosing regimens of oral SCY-078 
Secondary Objectives: 
• 
To evaluate the efficacy of oral SCY-078 in subjects with AVVC based on mycological and 
clinical outcomes 
• 
To evaluate the safety and tolerability of different dose levels and dosing regimens of oral 
SCY-078 in subjects with AVVC 
Exploratory Objectives: 
• 
To explore the efficacy of SCY-078 in subjects with AVVC based on potassium hydroxide 
(KOH) testing at the TOC visit 
• 
To explore the efficacy of SCY-078 in subjects with AVVC based on additional clinical 
outcomes 
• 
To explore the prevalence of Candida species among subjects with AVVC 
• 
To explore the in vitro activity of SCY-078 against baseline Candida spp. isolates 
• 
To explore clinical and mycological outcomes by Candida species  
• 
To evaluate the pharmacokinetics (PK) of SCY-078 after oral administration of different 
dose levels and dosing regimens in subjects with AVVC 


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Primary Endpoints: 
• 
 Efficacy as measured by the percentage of subjects with clinical cure (complete resolution 
of signs and symptoms) at the test-of-cure (TOC) visit  
Secondary Endpoints: 
Efficacy as measured by: 
• 
The percentage of subjects with mycological eradication (negative fungal culture) at the 
TOC visit  
• 
The percentage of subjects with both clinical cure and mycological eradication at the TOC 
and Follow-up (FU) visits. 
• 
The percentage of subjects with continued clinical response cure (continued absence of signs 
and symptoms) at the FU visit.  
• 
The time to resolution of signs and symptoms after initiation of study drug 
Safety and tolerability as measured by: 
• 
AEs, treatment discontinuations, vital signs, physical examination and safety laboratory tests  
Exploratory Endpoints: 
• 
Percentage of subjects with a negative KOH test at the TOC visit 
• 
Percentage of subjects who are free of signs and symptoms at the FU visit. 
• 
Percentage of subjects by Candida species infection at Baseline 
• 
Percentage of isolates susceptible to SCY-078 and fluconazole 
• 
Percentage of subjects with clinical cure (complete resolution of signs and symptoms) at 
TOC by Candida species 
• 
Percentage of subjects with mycological eradication (negative fungal culture) at TOC by 
Candida species 
• 
Determination of the PK parameters (maximum concentration [Cmax] and area under the 
concentration-time curve [AUC]) for each dosing regimen and evaluation of the 
dose/exposure relationship relative to clinical outcome 
Study Phase: Phase 2 
Study Design: 
This is a multicenter, randomized, double-blind, double-dummy, active-controlled, dose-finding 
study to compare the efficacy, safety and tolerability of oral SCY-078 compared to oral 
fluconazole in adult female subjects 18 years and older with moderate to severe AVVC. 
Approximately 180 eligible subjects (30 subjects per treatment group) will be enrolled and 
randomized into the study. 
The primary objective of this study is to identify the recommended dose of oral SCY-078 in 
subjects with moderate to severe AVVC by comparing the efficacy of different dose levels and 
dosing regimens of SCY-078. 
The study will consist of a Screening visit, a Baseline visit on Day 1, a study visit on Day 3 


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(which will consist of an on-site visit for PK sampling for a subset of subjects and a phone contact 
for all other subjects), a TOC visit (which will include PK sampling for the PK Subset of 
subjects) on Day 10 (±2) and a FU visit on Day 25 (+4). The Screening and Baseline visits may 
be combined. Efficacy, safety, tolerability and PK assessments will be conducted for the study.  
Efficacy will be determined primarily by the percentage of subjects with clinical cure (complete 
resolution of signs and symptoms) at the TOC visit. Secondary efficacy endpoints will include 
mycological eradication (negative fungal culture) at the TOC visit, a composite endpoint of both 
clinical cure and mycological eradication at the TOC and FU visits, continued clinical response 
cure (continued absence of signs and symptoms) at the FU visit, and time to resolution of signs 
and symptoms after initiation of study drug. Other efficacy endpoints will also be explored. 
Safety and tolerability will be evaluated throughout the study, including the following 
parameters: physical exam, vital signs, adverse events (AEs), treatment discontinuations, and 
safety laboratory tests. A subset of approximately 60 subjects will also undergo blood sampling 
for PK analyses of SCY-078 in plasma. 
At Screening, subjects who are experiencing vulvovaginal symptoms will be evaluated by the 
investigator, who will obtain a vaginal sample for local KOH testing and for fungal culture and 
species identification by the central laboratory. Susceptibility testing will be done at the central 
laboratory for all positive cultures for Candida spp. Additional vaginal samples will be collected, 
if clinically indicated, to be examined for the presence of other pathogens (e.g., causative agents 
for bacterial vaginosis, Trichomonas, Herpes virus, N. gonorrhea, Chlamydia, human 
papillomavirus or other mixed infections) by a qualified laboratory and for the determination of 
vaginal pH by the investigator. The investigators and the subjects will rate the signs (edema, 
erythema and excoriation) and symptoms (itching, burning and irritation) of infection, 
respectively, on a standardized vulvovaginal signs and symptoms scale (the Vulvovaginal Signs 
and Symptoms [VSS] Scale). Safety procedures, including an abbreviated physical exam, vital 
signs, laboratory tests and a pregnancy test will also be performed. To be eligible for inclusion, 
subjects must have a minimum composite score of vulvovaginal signs and symptoms ≥7 with at 
least 2 signs or symptoms having a score of 2 (moderate) or greater in the VSS Scale, a positive 
KOH test and a normal vaginal pH (≤4.5). 
At the Baseline visit (which may be combined with the Screening visit), eligible subjects will be 
randomized in equal allocation (at a 1:1:1:1:1:1 ratio) to one of the following 6 active treatment 
groups (5 experimental groups and 1 active comparator group):  
• 
Treatment Group 1: oral SCY-078 750 mg QD on Day 1 only 
• 
Treatment Group 2: oral SCY-078 300 mg BID on Day 1 only 
• 
Treatment Group 3: oral SCY-078 450 mg BID on Day 1 only 
• 
Treatment Group 4: oral SCY-078 150 mg BID on Days 1 to 3 
• 
Treatment Group 5: oral SCY-078 300 mg BID on Days 1 to 3 
• 
Treatment Group 6: oral fluconazole 150 mg QD on Day 1 only 
Subjects will receive randomized treatment from Day 1 through Day 3. For the purpose of 
maintaining treatment blinding, all randomized subjects will receive matching SCY-078 placebo 
tablets and/or matching fluconazole placebo capsules as needed based on treatment assignment, 
in a double-dummy fashion. During treatment days, subjects will rate their vulvovaginal 
symptoms and record dosing details, AEs and concomitant medication use daily on subject 
diaries. On Day 3, a PK Subset consisting of 10 subjects per treatment group (total of 60 subjects) 
will visit the site to have PK samples drawn pre-dose (immediately before dosing) and at 2-6 
hours’ post-dose of either the morning or evening dose.  Day 3 will be an on-site visit for PK 


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subjects and a phone contact visit (with a window of +3 days) for non-PK subjects.  All subjects 
(both PK and non-PK subjects) will continue to take their assigned study treatment and rate their 
symptoms of infection within their subject diaries. Treatment compliance will be reviewed either 
on site or by phone for all subjects. Study drug may be collected from PK subjects who have 
completed study drug dosing at the time of this visit. 
At the TOC visit (Day 10 [±2]) vaginal samples will be obtained for local KOH testing and for 
fungal culture by the central laboratory. In addition, susceptibility testing will be done at the 
central laboratory for all positive cultures for Candida spp. The investigators and the subjects 
will rate the signs and symptoms of infection, respectively, on the VSS Scale. An abbreviated 
physical exam, vital sign measurements and safety laboratory tests will also be performed. 
Additionally, a single PK sample will be obtained at any convenient time of the day from the PK 
Subset only. For the PK Subset, the TOC visit must occur as close to Day 10 as possible. All 
subjects will return their subject diaries. Compliance with study drug dosing will be evaluated 
and study drug will be collected for all subjects who did not return their study drug on Day 3.   
At the FU (Day 25[+4])) visit, vaginal samples will be obtained for local KOH testing and for 
fungal culture by the central laboratory. In addition, susceptibility testing will be done at the 
central laboratory for all positive cultures for Candida spp. The investigators and the subjects 
will rate the signs and symptoms of infection, respectively, on the VSS Scale to evaluate clinical 
outcome. 
AEs and prior/concomitant medications will be assessed and documented at all visits. 
Target Population: Adult female subjects 18 years and older, with moderate to severe AVVC 
KEY Inclusion Criteria 
Subjects must fulfill all of the following KEY criteria to be eligible for study admission: 
1. 
Subject is a female subject 18 years and older and is in good general health based on medical 
history, physical examination, vital sign measurements and safety laboratory tests 
performed at the Screening visit and/or prior to administration of the initial dose of study 
drug. 
2. 
Subject has a diagnosis of symptomatic AVVC that meets the following criteria:  
a. 
Moderate to severe disease, defined as a minimum composite vulvovaginal signs and 
symptoms score of ≥7 with at least 2 signs or symptoms having a score of 2 (moderate) 
or greater in the VSS Scale at Baseline 
b. 
Positive microscopic examination with 10% KOH in a vaginal sample collected at 
Screening revealing yeast forms (hyphae/pseudohyphae) or budding yeasts 
c. 
Normal vaginal pH (≤4.5) 
KEY Exclusion Criteria 
A subject will be excluded from participation in the study if she meets any of the following KEY 
exclusion criteria:  
1. Subject has any vaginal condition other than AVVC that may interfere with the diagnosis or 
evaluation of response to therapy, such as suspected or confirmed concurrent causes of 
vulvovaginitis and/or cervicitis including bacterial vaginosis, Trichomonas, active Herpes 
virus, N. gonorrhea, Chlamydia, active human papillomavirus or other mixed infections. 


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2. Subject requires treatment with the prohibited medications (including prescription and over-
the-counter medications, supplements, and herbal products) listed in Section 21.0 (Appendix 
A), during the following timeframes: 
a. Systemic and/or topical (vaginal) antifungal treatment, including prescription or over-
the-counter products, within 28 days prior to enrollment if administered for the treatment 
of VVC and during the study for all cases 
b. CYP3A4/5 inducers and strong time-dependent CYP3A4/5 inhibitors during the 14 days 
prior to enrollment and during study treatment 
c. Strong or moderate reversible CYP3A4/5 inhibitors, including azoles and grapefruit 
juice, during 48 hours prior to enrollment and during study treatment until TOC 
d. Select CYP2C8 substrates during the 48 hours prior to enrollment or during study 
treatment 
e. Select P-gp substrates during the 48 hours prior to enrollment or during study treatment 
SCY-078 
3. Subject is actively menstruating at the time of the Baseline visit. 
4. Subject has uncontrolled diabetes mellitus. 
5. Subject has a vaginal sample with pH >4.5. 
6. Subject has a history of or an active cervical/vaginal cancer. 
Study Drugs: SCY-078 (150-mg tablets), SCY-078 matching placebo tablets, fluconazole 
(150-mg capsules) and fluconazole matching placebo capsules. 
SCY 078 citrate drug product for oral administration will be supplied as a tablet containing 150 
mg of SCY-078 active ingredient on a free-base basis. In addition to the active ingredient, the 
tablet formulation also contains silicified microcrystalline cellulose, crospovidone, mannitol, 
colloidal silicon dioxide, magnesium stearate (non-bovine) and butylated hydroxyanisole. 
Fluconazole study drug will be sourced commercially and will be modified (encapsulated) for 
the purpose of blinding. Fluconazole will be provided as a capsule containing 150 mg of active 
ingredient. 
The randomized study drugs, SCY-078 (150-mg tablets), SCY-078 matching placebo tablets, 
fluconazole (150-mg capsules) and fluconazole matching placebo capsules, will be provided by 
the sponsor. 
Study Treatment Groups: Randomized subjects will receive active treatment as detailed 
below. For all treatment groups, study drug must be administered 30 minutes before or 2 hours 
after any meal and must be taken with approximately 8 oz./240 mL of water. 
Treatment Group 1 (oral SCY-078 750 mg once daily [QD] on Day 1 only):  
Subjects randomized to Treatment Group 1 will receive oral SCY-078 750 mg QD on Day 1 
only (total daily dose of 750 mg). On randomization day (Baseline [Day 1]), subjects will take 5 
tablets of SCY-078 150 mg in the morning.  
Treatment Group 2 (oral SCY-078 300 mg twice daily [BID] on Day 1 only):  
Subjects randomized to Treatment Group 2 will receive oral SCY-078 300 mg BID on Day 1 
only (total daily dose of 600 mg). On randomization day (Baseline [Day 1]), subjects will take 2 
tablets of SCY-078 150 mg in the morning and 2 tablets of SCY 078 150 mg in the evening, 
approximately 12 hours apart.  


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Treatment Group 3 (oral SCY-078 450 mg BID on Day 1 only):   
Subjects randomized to Treatment Group 3 will receive oral SCY-078 450 mg BID on Day 1 
only (total daily dose of 900 mg). On randomization day (Baseline [Day 1]), subjects will take 3 
tablets of SCY-078 150 mg in the morning and 3 tablets of SCY-078 150 mg in the evening, 
approximately 12 hours apart.  
Treatment Group 4 (oral SCY-078 150 mg BID on Days 1 to 3):   
Subjects randomized to Treatment Group 4 will receive oral SCY-078 150 mg BID on Day 1 
through Day 3 (total daily dose of 300 mg). On randomization day (Baseline [Day 1]), subjects 
will take 1 tablet of SCY-078 150 mg in the morning and 1 tablet of SCY-078 150 mg in the 
evening, approximately 12 hours apart. Over the next 2 consecutive days (Day 2 and Day 3), 
subjects will take their dose in the morning upon arising and in the evening, approximately 12 
hours apart.  
Treatment Group 5 (oral SCY-078 300 mg BID on Days 1-3):  
Subjects randomized to Treatment Group 5 will receive oral SCY-078 300 mg BID on Days 1 3 
(total daily dose of 600 mg). On randomization day (Baseline [Day 1]), subjects will take 2 
tablets of SCY-078 150 mg in the morning and 2 tablets of SCY-078 150 mg in the evening, 
approximately 12 hours apart. Over the next 2 consecutive days (Day 2 and Day 3), subjects will 
take their dose in the morning upon arising and in the evening, approximately 12 hours apart.  
Treatment Group 6 (oral fluconazole 150 mg QD on Day 1 only):  
Subjects randomized to Treatment Group 6 will receive oral fluconazole 150 mg QD on Day 1 
only (total daily dose of 150 mg). On randomization day (Baseline [Day 1]), subjects will take 1 
capsule of fluconazole 150 mg in the morning.  
Study Blinding, Randomization: This is a randomized, double-blind, double-dummy study.  
All site and sponsor personnel will be blinded to treatment assignment, except for a member of 
the sponsor personnel or a sponsor representative who will be involved in safety activities. 
Approximately 180 eligible subjects will be enrolled and randomized in equal allocation to one 
of the 6 study treatment groups (5 experimental groups and 1 active comparator group). For the 
purpose of maintaining treatment blinding, all randomized subjects will receive matching SCY-
078 placebo tablets and/or matching fluconazole placebo capsules as needed based on treatment 
assignment, in a double-dummy fashion. 
All randomization of subjects will be managed electronically through an interactive voice 
response system (IWRS). There will be no stratification for this study.  
Study Evaluations: 
Pharmacokinetic Evaluations: 
Blood samples to measure SCY-078 and possible metabolite plasma concentrations will be 
drawn on Day 3 and Day 10 from the PK Subset, which will consist of 10 subjects per treatment 
group (total of 60 subjects).  On Day 3, samples will be collected at pre-dose (immediately before 
dosing) and at 2-6 hours’ post-dose of either the morning or evening study drug dose. On Day 10, 
a single PK sample will be collected. For the PK Subset, the TOC visit must occur as close to 
Day 10 as possible. This sample may be collected at any time of the day. Blood will be collected 
from all six treatment groups to keep the treatment blinding but only samples from subjects 
assigned to SCY-078 will be analyzed for PK. 
Efficacy Evaluations: 
The primary efficacy endpoint of the study is the percentage of subjects with clinical cure 
(complete resolution of signs and symptoms) at the TOC visit. Secondary efficacy endpoints 


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include mycological eradication (negative fungal culture) at the TOC visit, a composite endpoint 
of both clinical cure and mycological eradication at the TOC and FU visits, continued clinical 
response (continued absence of signs and symptoms) at the FU visit and the time to resolution 
of signs and symptoms after initiation of study drug. The percentage of subjects with a negative 
KOH test at the TOC visit, the percentage of subjects who are free of signs and symptoms at the 
FU visit, the percentage of subjects by Candida species infection at Baseline, the percentage of 
isolates susceptible to SCY-078 and fluconazole, the percentage of subjects with clinical cure 
(complete resolution of signs and symptoms) at TOC by Candida species, and the percentage of 
subjects with mycological eradication (negative fungal culture) at TOC by Candida species will 
be evaluated as exploratory efficacy endpoints. 
The following treatment outcome definitions will be used for the assessment of efficacy: 
Clinical Outcomes 
•  Clinical cure: Complete resolution of signs and symptoms of vulvovaginal infection without 
need for further antifungal treatment. Specifically, for complete resolution, any sign or 
symptom should be absent (score = 0) by the TOC visit. 
•  Clinical failure: No response to therapy or incomplete resolution of signs and symptoms or 
need for additional vulvovaginal or systemic antifungal therapy. If the subject receives or self-
administers topical drug therapy for the treatment of vulvovaginal irritation/pruritus such as 
topical analgesic or corticosteroid after completing treatment with the study drug and before 
the TOC visit, the subject is considered a clinical failure. 
• Continued Clinical Response: continued absence of signs and symptoms of vulvovaginal 
infection in subjects who achieved clinical cure at the TOC visit. 
•  Free of Signs and Symptoms: absence of signs and symptoms of vulvovaginal infection at the 
FU visit. 
Mycological Outcomes 
•  Mycological eradication: A subject with negative culture (no growth) for Candida species.  
•  Mycological persistence: A subject with a positive culture for Candida species. 
Safety Evaluations: 
Safety will be evaluated throughout the study, including the following parameters: AEs, physical 
examination, vital signs, safety laboratory tests and treatment discontinuations. 
Statistical Analyses: 
All statistical processing will be performed using SAS® version 9.3 or later, unless otherwise 
stated.  All statistical tests will be two-sided and interpreted at a 5% significance level. The study 
is not powered for formal statistical comparisons. 
Descriptive statistics (i.e., mean, standard deviation, median, minimum, maximum, etc.) will be 
provided for all continuous variables; frequencies and percentages will be tabulated for incidence 
and categorical variables.  For parameters measured over time, observed values and changes 
from baseline will be described for each time point. 
All analyses will be presented by treatment group.  Unless otherwise stated, data will be analyzed 
as is with no imputation.  No adjustment for multiplicity will be employed. 
A Statistical Analysis Plan (SAP) describing all statistical analyses in detail will be provided as 
a separate document. The SAP will be finalized prior to unblinding of the study treatments. 


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Sample Size Determination 
This is an exploratory study and no formal sample size calculation was performed. 
Approximately 180 subjects will be enrolled and randomized in an equal allocation (at a 
1:1:1:1:1:1 ratio) to the six study treatment groups. Thirty subjects per group are estimated to be 
adequate to perform an initial assessment of the safety and tolerability as well as the potential 
efficacy of SCY-078 in subjects with AVVC. 
Analysis Populations 
Intent-to-Treat (ITT) Population: All randomized subjects. 
Modified Intent-to-Treat (mITT) Population: All randomized subjects who have a positive KOH 
test and a confirmed positive mycological culture for yeast at Baseline. 
Per-Protocol (PP) Population: All mITT subjects who have completed the study drug treatment, 
who have a TOC evaluation AND who have no major protocol deviations.  
PK Population: All randomized subjects who received study drug and provided at least one PK 
sample. 
Safety Population: All randomized subjects who received at least one dose of study drug and 
who have at least one post-Baseline evaluation. 
Pharmacokinetic Analyses 
PK parameters will be estimated using Population PK (Pop PK) analysis in NONMEM as 
detailed in the SAP. The PK analyses will be done using the PK Population.  
An evaluation of exposure for each dosing regimen relative to clinical cure will be performed.  
The concentration versus time data from the PK samples collected in this study will be analyzed 
using a Pop PK model to predict AUC and Cmax (as appropriate). A Pop PK modeling strategy is 
required because the sampling time points will not support a standalone PK analysis, and hence, 
the data from this study will be pooled with data from other oral studies to predict AUC and Cmax 
on Day 1 of treatment.  A stand-alone Population PK report will prepared to describe the analysis 
performed on the PK samples collected from this study. 
Further analysis of possible metabolites may be performed. 
Efficacy Analyses 
The efficacy analyses will be conducted using the mITT (primary analysis population), ITT and 
PP populations. The efficacy parameters will be evaluated comparing each SCY-078 treatment 
group (and all treatment groups combined) versus the active comparator (fluconazole) group. 
The primary endpoint (clinical cure at TOC) will be analyzed using a Cochran-Mantel-Haenszel 
row mean scores test. Pairwise treatment comparisons of SCY-078 vs. fluconazole will be 
performed using a Fisher’s Exact test; p-values and 95% confidence intervals will be presented. 
Subjects whose results are missing at Day 10 (TOC) will be imputed as failures in the analysis. 
A sensitivity analysis will be performed where subjects with missing values will be removed 
from the analysis. 
For continuous efficacy endpoints, the Student’s t-test will be used for pairwise treatment 
comparisons of SCY-078 vs. fluconazole; p-values and 95% confidence intervals will be 
presented for the differences between treatment groups. For categorical endpoints, Fisher’s Exact 
test will be performed, and p-values and 95% confidence intervals will be presented. The time 
to resolution of signs and symptoms after initiation of study drug will be analyzed using Kaplan-
Meier methods. 


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Safety Analyses 
Safety analyses will be conducted using the safety population. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 
19.1 or higher. The incidence and severity of treatment-emergent AEs and SAEs and their 
relationship to treatment will be summarized by system organ class and preferred term. The 
percentage of subjects who discontinued study treatment and the reasons for discontinuation will 
be summarized by treatment group. 
Safety laboratory evaluations and vital signs will be summarized as observed values and as 
changes from baseline. In addition, shifts (with respect to the reference range) from baseline will 
be presented by treatment group for selected laboratory tests. 


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6.0 Schematic of Study Design 
 
 
 
 
 
Figure 1 
Schematic of Study Design 


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7.0 Background Information and Scientific Rationale 
7.1 
Background Information 
Vulvovaginal Candidiasis 
Vulvovaginal candidiasis (VVC) is a common fungal infection caused by Candida spp and is a 
significant morbidity condition in women from all social classes. 
Information on the incidence of VVC is incomplete, since the disease is not a reportable entity and 
data collection is hampered by inaccuracies of diagnosis and the use of non-representative study 
populations.1 VVC affects 70%–75% of women at least once during their lives, most frequently 
young women of childbearing age. Approximately 40%–50% of women will experience a 
recurrence2 and 5% to 8% of adult women have a recurrent vulvovaginal candidiasis.3 The reported 
incidence goes from 15% to 30%.4,5  
Current treatments for VVC include topical antifungals and the use of prescription oral antifungals 
such a single doses of fluconazole.  In two vaginal candidiasis studies conducted with fluconazole, 
the therapeutic cure rate, defined as the resolution of signs and symptoms of vaginal candidiasis 
along with negative KOH examination and negative culture for Candida, was achieved by 55% of 
subjects receiving single doses of fluconazole 150 mg.  The therapeutic cure rate is reduced to 
40% in subjects with a history of recurrent vaginitis.6,8  Although a single dose of fluconazole is 
able to provide an acceptable therapeutic outcome for more than half of the treated individuals, the 
emergence of fluconazole resistance among C. albicans isolates and the frequency of cases caused 
by C. glabrata, a strain naturally less susceptible to fluconazole, signals the need for new 
therapeutic approaches.  
Additionally, recurrence of VVC after fluconazole therapy is not uncommon and these 
exacerbations often involve the same microorganism identified in the initial episode, suggesting 
that a small number of C. albicans remain as a reservoir in the vagina after completion of azole 
therapy, becoming the source of subsequent exacerbations. This may be explained by the fact that 
azoles are fungistatic, which means that they slow the growth of, but do not kill, the fungus and 
azoles are not active against certain species of Candida that cause VVC. 
New curative approaches are needed, particularly involving agents with fungicidal activity (i.e., 
that are able to kill the fungus) and activity against fluconazole-resistant strains, so that the 
causative yeasts can be eradicated. A new therapeutic approach with these characteristics would 
be expected to result in improved short-term and potentially long-term outcomes for this condition.   
This study aims to identify the efficacious dose of SCY-078, as a new class of antifungal agent 
with fungicidal activity against Candida spp. in the treatment of patients with VVC. 
The glucan synthesis inhibitor SCY-078 
SCY-078 is a member of a new class of antifungal agents and is an orally active, semi-synthetic, 
triterpene derivative of the natural product enfumafungin. SCY-078 is a structurally distinct class 
of glucan synthesis inhibitor (GSI) that inhibits the synthesis of the fungal cell wall polymer β-


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(1,3)-D-glucan. Time-kill studies have demonstrated that SCY-078 has in vitro fungicidal activity 
against Candida spp. isolates similar to that observed with the echinocandins.  
SCY-078 is being developed as the first oral and intravenous (IV) GSI for the treatment and 
prevention of fungal infections caused by Candida and Aspergillus species with the potential to 
provide the therapeutic advantages of both an IV and oral formulation.  
Antifungal activity  
The spectrum and potency of activity of SCY-078 has been evaluated by numerous independent 
laboratories against an extensive panel of clinically relevant yeast and mold isolates using the 
Clinical and Laboratory Standards Institute (M27-A3 guidelines)7 and European Committee on 
Antimicrobial Susceptibility Testing methods. Overall, the epidemiological studies have 
demonstrated that SCY-078 has potent, broad-spectrum activity against the majority of the clinical 
isolates tested. These studies have laid the foundation in support of the use of SCY-078 for the 
treatment of invasive fungal infections.  
Activity against Candida spp. 
SCY-078 has been evaluated against >1200 Candida isolates, including all clinically relevant 
species, more than 300 C. glabrata isolates and 16 C. auris isolates. These in vitro studies have 
demonstrated the broad spectrum of anti-Candida activity of SCY-078. Additionally, SCY-078 
demonstrated in vitro activity against pre-formed biofilms, which is a relevant feature when 
addressing catheter-related Candida infections. Studies conducted with azole- and echinocandin-
resistant strains have shown that SCY-078 retains activity (i.e., no significant change in minimum 
inhibitory concentration when compared to wild type) against >90% of azole-resistant strains and 
>70% of Candida strains with FKS mutations commonly associated with echinocandin resistance. 
Interestingly, although SCY-078 and the echinocandins share a similar mechanism of action (β-
[1,3]-D-glucan synthesis inhibition), their clearly different molecular structure provides them with 
some differentiating characteristics in terms of microbiological activity.  
SCY-078 was evaluated in vitro against >170 clinical isolates of echinocandin-resistant strains of 
Candida spp., >95% of which contained mutations in the FKS gene. Overall, SCY-078 was active 
against the majority of the echinocandin-resistant strains tested. Significantly, SCY-078 was active 
against approximately 70% of the isolates containing the most commonly reported FKS mutation 
associated with echinocandin resistance in C. glabrata (S663P in FKS2 and S645P in FKS1). 
Selection of SCY-078 resistance in vitro occurs at a low frequency. A deletion at position F659 in 
FKS2 of C. glabrata was the predominant mutation observed in these studies; notably, SCY-078 
did not select for mutations at positions S663 or S645. These results suggest that SCY-078 inhibits 
glucan synthase in a manner different from that of echinocandins.  
The in vitro studies also included several multidrug-resistant isolates. Consistent with the data 
described above, SCY-078 was active against >70% of these isolates. SCY-078 has also 
demonstrated a potent activity against life-threatening and multi-drug-resistant C. auris strains 


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over 16 different C. auris isolates, at concentrations indicative of potential clinically relevant 
effect.7 C. auris has been recently highlighted as a clinical alert by the CDC because of the global 
emergence of this fungal infection with limited therapeutic options and high mortality.  
Activity against Aspergillus spp. 
The in vitro activity of SCY-078 has been evaluated against >150 clinical Aspergillus isolates, 
including most clinically relevant species and azole-resistant strains. The results demonstrated 
potent activity of SCY-078 against all of the strains tested.  
Murine models of invasive fungal infections  
The antifungal efficacy of SCY-078 has been evaluated in several murine models of disseminated 
candidiasis and aspergillosis. In a disseminated C. albicans model, SCY-078 was more active than 
fluconazole at all doses. Murine models of SCY-078 in disseminated candidiasis caused by 
C. glabrata and C. tropicalis indicated activity across multiple Candida species. The SCY-078 
area under the concentration-time curve (AUC) in plasma necessary to achieve target efficacy in 
these models was estimated to be 15.4 ± 2.2 μM•hr.  
Nonclinical experience  
Toxicology studies in rats and dogs have been conducted with SCY-078 following oral 
administration for up to 90 days. The results from the non-clinical safety program are supportive 
of the doses and treatment duration intended in this study.  
The in vitro studies indicated that SCY-078 metabolism was predominantly oxidative, with 
cytochrome P450 (CYP) 3A being the primary enzyme involved in its oxidative metabolism. 
Strong inhibitors of CYP3A would be expected to increase plasma levels of SCY-078; therefore, 
the concurrent administration of SCY-078 with such inhibitors is prohibited.  
Clinical experience  
To date, over 300 subjects and patients have received either oral or IV formulations of SCY-078 
in Phase 1 and Phase 2 studies.  
SCY-078 was generally well tolerated following single oral doses of up to 1600 mg and multiple 
oral doses of up to 800 mg/day for 28 consecutive days in Phase 1 studies. Reported adverse events 
(AEs) after oral administration have been generally transient and primarily mild to moderate in 
intensity. The most frequently reported AEs have been mild gastrointestinal events (nausea, 
vomiting, diarrhea and abdominal pain).  
A Phase 2 study of oral SCY-078 as step-down therapy from IV echinocandin in patients with 
invasive candidiasis has been completed. Following three to ten days of IV echinocandin therapy, 
21 patients received either SCY-078 or fluconazole. SCY-078 was well tolerated, with an AE 
profile typical of this population and comparable to the SOC. The results from this study also 


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indicated that the higher dose of SCY-078 tested (750 mg QD) is predicted to achieve the target 
exposure at steady state in the majority of patients.  
A Phase 2 proof-of-concept study of oral SCY-078 in patients with acute vulvovaginal candidiasis 
(AVVC) has also been completed. In this multicenter, randomized, active-controlled, evaluator-
blinded study of oral SCY-078 compared to oral fluconazole in adult female patients with AVVC, 
96 patients with an acute, moderate to severe, symptomatic episode of vulvovaginal candidiasis 
were randomized in a 1:1:1 ratio to receive either oral SCY-078 750 mg with a 1250 mg loading 
dose for three days, oral SCY-078 750 mg with a 1250 mg loading dose for five days or a single 
dose of oral fluconazole. SCY-078 was well tolerated, with the most common AEs being mild 
gastrointestinal events. The high clinical cure rates observed in this study are supportive of the 
clinically relevant antifungal activity of SCY-078 in this form of Candida infection.  
Several drug-drug interaction studies have been conducted. Ketoconazole (a strong inhibitor of 
CYP3A) induces a significant (5-fold) increase in SCY-078 exposure, while diltiazem (a moderate 
inhibitor of CYP3A) induces a mild to moderate (<3-fold) increase in SCY-078 exposure. 
SCY-078 did not have any effect on rosiglitazone (a CYP2C8 substrate) exposure, had only a mild 
effect (less than a 0.5-fold increase) on the AUC of tacrolimus (a CYP3A and P-glycoprotein 
[P-gp] substrate) and had no effect on the maximum concentration (Cmax) of tacrolimus. 
SCY-078 has the potential to be an important addition to the antifungal treatment arsenal by 
providing potent activity against the full spectrum of Candida species, including difficult-to-treat 
organisms, and by affording the added flexibility of both oral and IV formulations.  
For additional information on SCY-078, please refer to the Investigator´s Brochure (IB).  
7.2 
Rationale for the Study 
This study is being performed to evaluate the efficacy and safety of different dose levels and dosing 
regimens of SCY-078 as compared to fluconazole in adult female patients 18 years and older with 
moderate to severe AVVC. 
Rationale for Study Indication and Population 
Considering the properties of SCY-078 as a potent antifungal compound, with fungicidal activity 
against Candida spp., it will represent an important non-azole alternative treatment for subjects 
suffering from AVVC.  
Subjects with moderate to severe AVVC are intended for this study to facilitate the identification 
of a clinically meaningful effect of SCY-078 with a limited sample size.   
Rationale for Selected Dose Levels and Dosing Regimens 
The SCY-078 dose levels and dosing regimens selected for this study (750 mg QD for 1 day, 
300 mg twice daily [BID] for 1 day [total daily dose of 600 mg], 450 mg BID for 1 day [total daily 


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dose of 900 mg], 150 mg BID for 3 days [total daily dose of 300 mg] or 300 mg BID for 3 days 
[total daily dose of 600 mg]) are in the range of doses that have been well tolerated in Phase 1 
investigations. Since the estimated effective exposure of SCY-078 for vulvovaginal candidiasis 
has not been determined, this study will contribute to a better understanding of the exposures that 
may be associated with clinical efficacy for this indication to guide further investigations.   
The dose selected for the active comparator of this study (fluconazole) is one single oral dose of 
150 mg, which is the recommended and approved dose for this indication.  
Rationale for Study Endpoints 
The primary endpoint for the study is clinical cure (complete resolution of signs and symptoms) 
of the acute symptomatic episode at the test-of-cure (TOC) visit on Day 10 (±2), which is in line 
with current regulatory guidance for this condition.9 The secondary efficacy endpoints will include 
mycological eradication (negative fungal culture) at TOC, a composite endpoint of both clinical 
cure and mycological eradication at the TOC and FU visits, continued clinical response (continued 
absence of signs and symptoms) at the Follow-up (FU) visit on Day 25 (+4), and time to resolution 
of signs and symptoms, which are also in line with current guidelines. The safety and tolerability 
of SCY-078 will also be evaluated as secondary objectives. Other objectives of the study will be 
to explore the efficacy of SCY-078 based on KOH testing at the TOC visit and based on additional 
clinical outcomes (clinical response regardless of clinical outcome at TOC) at the FU visit, to 
explore the prevalence of different Candida species, to explore the in vitro activity of SCY-078 
against baseline Candida spp. isolates, to explore clinical and mycological outcomes by Candida 
species, and to evaluate the PK of SCY-078.  
Rationale for Study Design 
This trial is being conducted as a double-blind, double-dummy study. This design is considered an 
appropriate design for this indication and phase of investigation, and will use matching SCY-078 
and fluconazole placebo to accommodate the differences in the dosing regimens and formulations 
of SCY-078 and the comparator (fluconazole).  
The data generated from this study will provide an initial characterization of the safety and 
tolerability of SCY-078 in subjects with AVVC, and will provide an initial indication of the most 
effective dosing regimen with efficacy of SCY-078 in this condition. Results from this study will 
guide subsequent phases of development for this indication.  


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8.0 Study Objectives 
8.1 
Primary Objectives 
• To identify the recommended dose of oral SCY-078 in subjects with moderate to severe AVVC 
by comparing the efficacy of different dose levels and dosing regimens of oral SCY-078  
8.2 
Secondary Objectives 
• To evaluate the efficacy of oral SCY-078 in subjects with AVVC based on mycological and 
clinical outcomes 
• To evaluate the safety and tolerability of different dose levels and dosing regimens of oral 
SCY-078 in subjects with AVVC 
8.3 
Exploratory Objectives 
• To explore the efficacy of SCY-078 in subjects with AVVC based on potassium hydroxide 
(KOH) testing at the TOC visit 
• To explore the efficacy of SCY-078 in subjects with AVVC based on additional clinical 
outcomes 
• To explore the prevalence of Candida species among subjects with AVVC 
• To explore the in vitro activity of SCY-078 against baseline Candida spp. isolates 
• To explore clinical and mycological outcomes by Candida species  
• To evaluate the PK of SCY-078 after oral administration of different dose levels and dosing 
regimens of SCY-078 in subjects with AVVC 
9.0 Study Endpoints 
9.1 
Primary Endpoints 
• Efficacy as measured by the percentage of subjects with clinical cure (complete resolution of 
signs and symptoms) at the TOC visit 
9.2 
Secondary Endpoints 
Efficacy as measured by: 
• The percentage of subjects with mycological eradication (negative fungal culture) at the TOC 
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• The percentage of subjects with both clinical cure and mycological eradication at the TOC and 
FU visits. 
• The percentage of subjects with continued clinical response (continued absence of signs and 
symptoms) at the Follow-up (FU) visit.  
• The time to resolution of signs and symptoms after initiation of study drug 
Safety and tolerability as measured by: 
• AEs, treatment discontinuations, vital signs, physical examination and safety laboratory tests 
9.3 
Exploratory Endpoints 
• Percentage of subjects with a negative KOH test at the TOC visit 
• Percentage of subjects who are free of signs and symptoms  at the FU visit 
• Percentage of subjects by Candida species infection at Baseline 
• Percentage of isolates susceptible to SCY-078 and fluconazole 
• Percentage of subjects with clinical cure (complete resolution of signs and symptoms) at TOC 
by Candida species 
• Percentage of subjects with mycological eradication (negative fungal culture) at TOC by 
Candida species 
• Determination of the PK parameters (Cmax and AUC) for each dosing regimen and evaluation 
of the dose/exposure relationship relative to clinical outcome 
10.0 Study Design 
10.1 Overall Description of the Study 
This is a multicenter, randomized, double-blind, double-dummy, active-controlled, dose-finding 
study to compare the efficacy, safety and tolerability of oral SCY-078 compared to oral 
fluconazole in adult female subjects 18 years and older with moderate to severe AVVC. 
Approximately 180 eligible subjects (30 subjects per treatment group) will be enrolled and 
randomized into the study. 
The primary objective of this study is to identify the recommended dose of oral SCY-078 in 
subjects with moderate to severe AVVC by comparing the efficacy of different dose levels and 
dosing regimens of SCY-078. 


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The study will consist of a Screening visit, a Baseline visit on Day 1, a study visit on Day 3 (which 
will consist of an on-site visit for PK sampling for a subset of subjects and a phone contact for all 
other subjects), a TOC visit (which will include PK sampling for the PK Subset of subjects) on 
Day 10 (±2) and a FU visit on Day 25 (+4). The Screening and Baseline visits may be combined.  
Efficacy, safety, tolerability and PK assessments will be conducted for the study.  
Efficacy will be determined primarily by the percentage of subjects with clinical cure (complete 
resolution of signs and symptoms) at the TOC visit. Secondary efficacy endpoints will include 
mycological eradication (negative fungal culture) at the TOC visit, a composite endpoint of both 
clinical cure and mycological eradication at the TOC and FU visits, continued clinical response 
(continued absence of signs and symptoms) at the FU visit, and the time to resolution of signs and 
symptoms after initiation of study drug. Other efficacy endpoints will also be explored. Safety and 
tolerability will be evaluated throughout the study, including the following parameters: physical 
exam, vital signs, AEs, treatment discontinuations and safety laboratory tests. A subset of 
approximately 60 subjects will also undergo blood sampling for PK analyses of SCY-078 in 
plasma.  
A summary description of the study visits and assessments is provided below. A schematic of the 
study design is available in Section 6.0. Detailed descriptions of study treatments and procedures 
are provided in Section 12.0 and Section 14.0, respectively.  
10.1.1 Study Visits 
Screening (Day -1) 
Consenting subjects who are experiencing vulvovaginal symptoms at Screening will be evaluated 
by the investigator, who will obtain a vaginal sample for local KOH testing and for fungal culture 
and species identification by the central laboratory. Susceptibility testing will be done at the central 
laboratory for all positive cultures for Candida spp. Additional vaginal samples will be collected, 
if clinically indicated, to be examined for the presence of other pathogens (e.g., causative agents 
for bacterial vaginosis, Trichomonas, Herpes virus, N. gonorrhea, Chlamydia, human 
papillomavirus or other mixed infections) by a qualified laboratory (central or local laboratory) 
and for the determination of vaginal pH by the investigator. The investigators and the subjects will 
rate the signs (edema, erythema and excoriation) and symptoms (itching, burning and irritation) of 
infection, respectively, on a standardized vulvovaginal signs and symptoms scale (the 
Vulvovaginal Signs and Symptoms [VSS] Scale) (see Appendix B). Safety procedures, including 
an abbreviated physical exam, vital signs, laboratory tests and a pregnancy test will also be 
performed. 
To be eligible for inclusion, subjects must have a minimum composite score of vulvovaginal signs 
and symptoms ≥7 with at least 2 signs or symptoms having a score of 2 (moderate) or greater in 
the VSS Scale, a positive KOH test and a normal vaginal pH (≤4.5). 


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Baseline (Day 1) 
At the Baseline visit (which may be combined with the Screening visit), eligible subjects will be 
randomized in equal allocation (at a 1:1:1:1:1:1 ratio) to one of the following 6 active treatment 
groups (5 experimental groups and 1 active comparator group):  
• Treatment Group 1: oral SCY-078 750 mg QD on Day 1 only 
• Treatment Group 2: oral SCY-078 300 mg BID on Day 1 only 
• Treatment Group 3: oral SCY-078 450 mg BID on Day 1 only 
• Treatment Group 4: oral SCY-078 150 mg BID on Days 1 to 3 
• Treatment Group 5: oral SCY-078 300 mg BID on Days 1 to 3 
• Treatment Group 6: oral fluconazole 150 mg QD on Day 1 only 
For the purpose of maintaining treatment blinding, all randomized subjects will receive matching 
SCY-078 placebo tablets and/or matching fluconazole placebo capsules as needed based on 
treatment assignment, in a double-dummy fashion. Study drug treatment will be dispensed on 
Day 1 and will be self-administered by the subjects from Day 1 (Baseline) through Day 3. Subjects 
will also be given subject diaries to rate their symptoms of infection on the VSS scale and to record 
dosing details, AEs and concomitant medication use daily from Day 1 through the TOC visit 
(Day 10). 
 
Day 3 
On Day 3, a PK Subset consisting of 10 subjects per treatment group (total of 60 subjects) will 
visit the site to have PK samples drawn pre-dose (immediately before dosing) and at 2-6 hours’ 
post-dose of either the morning or evening dose.  Day 3 will be an on-site visit for PK subjects and 
a phone contact visit (with a window of +3 days) for non-PK subjects.  All subjects (both PK and 
non-PK subjects) will continue to take their assigned study treatment and rate their symptoms of 
infection on their subject diaries. Treatment compliance will be reviewed either on site or by phone 
for all subjects.  Study drug may be collected from PK subjects who have completed study drug 
dosing at the time of this visit. 
 
 
TOC (Day 10) 
Vaginal samples will be obtained for local KOH testing and for fungal culture by the central 
laboratory. In addition, susceptibility testing will be done at the central laboratory for all positive 
cultures for Candida spp. The investigators and the subjects will rate the signs and symptoms of 
infection, respectively, on the VSS Scale. An abbreviated physical exam, vital sign measurements 
and safety laboratory tests will also be performed. Additionally, a single PK sample will be 
obtained at any convenient time of the day from the PK Subset only. For the PK Subset, the TOC 


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visit must occur as close to Day 10 as possible.  All subjects will return their subject diaries. 
Compliance with study drug dosing will be evaluated and study drug will be collected for all 
subjects who did not return their study drug on Day 3.   
 
FU (Day 25) 
Vaginal samples will be obtained for local KOH testing and for fungal culture by the central 
laboratory. In addition, susceptibility testing will be done at the central laboratory for all positive 
cultures for Candida spp. The investigators and the subjects will rate the signs and symptoms of 
infection on the VSS Scale to evaluate clinical outcome. 
  
All Visits 
AEs and prior/concomitant medications will be assessed and documented at all visits. 
10.1.2 Study Assessments 
The study will include efficacy, safety and PK assessments. 
 
Efficacy Assessments 
Treatment outcome will be assessed primarily based on clinical cure (complete resolution of signs 
and symptoms) at the TOC (Day 10) visit. Secondary efficacy endpoints will include mycological 
eradication (negative fungal culture) at the TOC visit, a composite endpoint of both clinical cure 
and mycological eradication at the TOC and FU visits, continued clinical response (continued 
absence of signs and symptoms) at the FU visit and time to resolution of signs and symptoms after 
initiation of study drug. Additionally, the percentage of subjects with a negative KOH test at the 
TOC visit, the percentage of subjects who are free of signs and symptoms at the FU visit, the 
percentage of subjects by Candida species infection at Baseline, the percentage of isolates 
susceptible to SCY-078 and fluconazole will be explored, the percentage of subjects with clinical 
cure (complete resolution of signs and symptoms) at TOC by Candida species and the percentage 
of subjects with mycological eradication (negative fungal culture) at TOC by Candida species will 
be evaluated as exploratory efficacy endpoints. 
 
Clinical Evaluation 
The signs (edema, erythema and excoriation or fissures) and symptoms (itching, burning and 
irritation) of infection will be assessed by the investigator and the subject, respectively, on the VSS 
Scale [provided in Appendix B]). The VSS Scale is a standardized, predefined scale where each 
sign and symptom will be given a numerical rating based on severity (absent = 0; mild = 1; 
moderate = 2; severe = 3) to calculate a total composite score. 
 


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Mycological Testing 
Mycological tests will include direct microscopic examination with 10% KOH and fungal cultures. 
KOH will be performed locally at Screening for the determination of subject eligibility and at the 
TOC and FU visits for the exploratory assessment of treatment outcome. Fungal cultures will be 
performed centrally at Screening for species identification and susceptibility testing and at the 
TOC and FU visits for the assessment of treatment outcome and susceptibility testing for subjects 
with positive cultures.  
 
Pharmacokinetic Assessments 
Blood samples will be drawn on Day 3 and Day 10 (±2) from the PK Subset (10 subjects per 
treatment group) for the determination of SCY-078 and possible plasma metabolite concentrations. 
For the PK Subset, the TOC visit must occur as close to Day 10 as possible.  Blood will be collected 
from all six treatment groups to keep treatment blinding but only samples from subjects assigned 
to SCY-078 will be analyzed for PK. 
 
Safety Assessments 
Safety procedures will include an abbreviated physical exam, vital signs, pregnancy test, safety 
laboratory tests, AEs and review of concomitant medication use. 
10.2 Blinding, Randomization and Stratification 
This is a randomized, double-blind, double-dummy study.  All site and sponsor personnel will be 
blinded to treatment assignment, except for a member of the sponsor personnel or a sponsor 
representative who will be involved in safety activities. 
Approximately 180 eligible subjects will be enrolled and randomized in equal allocation (at a 
1:1:1:1:1:1 ratio) to one of the 6 study treatment groups (5 experimental groups and 1 active 
comparator group). For the purpose of maintaining treatment blinding, all randomized subjects 
will receive matching SCY-078 placebo tablets and/or matching fluconazole placebo capsules as 
needed based on treatment assignment, in a double-dummy fashion. 
All randomization of subjects will be managed electronically through an interactive voice response 
system (IWRS). 
There will be no stratification for this study.  
10.3 Study Duration 
Each subject is expected to complete the study within approximately 30 days. 


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10.4 Number of Centers 
Approximately 20 study centers are expected to participate in subject enrollment and treatment. 
11.0 Study Population 
The study population will include adult female subjects 18 years and older, with moderate to severe 
AVVC. 
11.1 Inclusion Criteria 
Subjects must fulfill all of the following criteria to be eligible for study admission: 
1. Subject is a female subject 18 years and older and is in good general health based on medical 
history, physical examination, vital sign measurements and safety laboratory tests performed 
at the Screening visit and/or prior to administration of the initial dose of study drug. 
2. Subject has a diagnosis of symptomatic AVVC that meets the following criteria:  
a. 
Moderate to severe disease, defined as a minimum composite vulvovaginal signs and 
symptoms score of ≥7, with at least 2 signs or symptoms having a score of 2 (moderate) 
or greater in the VSS Scale at Baseline 
b. Positive microscopic examination with 10% KOH in a vaginal sample collected at 
Screening revealing yeast forms (hyphae/pseudohyphae) or budding yeasts 
c. 
Normal vaginal pH (≤4.5) 
3. Subject is not pregnant and is highly unlikely to become pregnant since she meets at least one 
of the following criteria:  
a. 
Subject is a female subject who is not of reproductive potential and is eligible without 
requiring the use of contraception. A female subject who is not of reproductive potential 
is defined as one who: (1) has reached natural menopause (defined as 6 months of 
spontaneous amenorrhea with serum follicle-stimulating hormone levels in the 
postmenopausal range as determined by the local laboratory, or 12 months of spontaneous 
amenorrhea); (2) is 6 weeks’ post-surgical bilateral oophorectomy with or without 
hysterectomy; or (3) has undergone bilateral tubal ligation. Spontaneous amenorrhea does 
not include cases for which there is an underlying disease that causes amenorrhea (e.g. 
anorexia nervosa). 
b. Subject is a female subject who is of reproductive potential and agrees to remain abstinent 
or use (or have her partner use) 2 acceptable methods of contraception starting from the 
time of consent through 28 days after the completion of study therapy. Acceptable 


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methods of birth control are intrauterine device, condom, hormonal contraceptives and 
vasectomy. 
Hormonal contraception, including but not limited to oral, injectable or implantable 
methods, are not acceptable as a single method of contraception because the effect of 
SCY-078 on the efficacy of oral contraceptive pills has not yet been established.   
Subjects must refrain from using any vaginal contraceptives as these may have an 
impact on the signs and symptoms of AVVC. 
Note: Women of childbearing potential must have a negative urine pregnancy test prior to 
enrollment (performed by the site’s local laboratory). 
4. Subject is able to understand and sign a written informed consent form (ICF), which must be 
obtained prior to treatment and any study-related procedures. 
5. Subject is able to understand and sign a consent or authorization form, which shall permit the 
use, disclosure and transfer of the subject’s personal health information (e.g., in the US Health 
Information Portability and Accountability Act Authorization form).  
6. Subject is able to understand and follow all study-related procedures including study drug 
administration. 
11.2 Exclusion Criteria 
A subject will be excluded from participation in the study if she meets any of the following 
exclusion criteria:  
1. Subject has any vaginal condition other than AVVC that may interfere with the diagnosis or 
evaluation of response to therapy, such as suspected or confirmed concurrent causes of 
vulvovaginitis and/or cervicitis including bacterial vaginosis, Trichomonas, active Herpes 
virus, N. gonorrhea, Chlamydia, active human papillomavirus or other mixed infections. 
2. Subject requires treatment with the prohibited medications (including prescription and over-
the-counter medications, supplements, and herbal products) listed in Section 21.0 (Appendix 
A), during the following timeframes: 
a. 
Systemic and/or topical (vaginal) antifungal treatment, including prescription or over-
the-counter products, within 28 days prior to enrollment if administered for the 
treatment of VVC and during the study for all cases 
b. CYP3A4/5 inducers and strong time-dependent CYP3A4/5 inhibitors during the 
14 days prior to enrollment and during study treatment 
c. 
Strong or moderate reversible CYP3A4/5 inhibitors, including azoles and grapefruit 
juice, during 48 hours prior to enrollment and during study treatment until TOC 


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d. Select CYP2C8 substrates during the 48 hours prior to enrollment or during study 
treatment 
e. 
Select P-gp substrates during the 48 hours prior to enrollment or during study treatment 
SCY-078 
3. Subject is actively menstruating at the time of the Baseline visit. 
4. Subject has uncontrolled diabetes mellitus. 
5. Subject has a vaginal sample with pH >4.5. 
6. Subject has a history of or an active cervical/vaginal cancer. 
7. Subject has a known hypersensitivity to SCY-078, fluconazole or any of the components of 
the formulation. 
8. Subject has a known human immunodeficiency virus infection and/or is receiving 
chemotherapy or has an illness that, in the judgment of the investigator, is serious enough to 
induce an immune deficiency. 
9. Subject has had any major illness within 30 days before Screening. 
10. Subject is pregnant or lactating. 
11. Subject has participated in any other investigational study within at least 30 days (or 5.5 half-
lives of the investigational product) before signing the ICF.  
12. Subject has received prior treatment with the study drug in a previous trial. 
13. Subject has any other condition or laboratory abnormality that, in the judgment of the 
investigator, would put the subject at unacceptable risk for participation in the study or may 
interfere with the assessments included in the study. 
14. Subject is an employee of SCYNEXIS, Inc., the investigator or the CRO involved in the study, 
or is an immediate family member (partner, offspring, parent, sibling, or sibling’s offspring) 
of an employee involved in the study. 
15. Subject is unlikely to comply with protocol requirements. 
 
11.3 Discontinuation Criteria 
A subject may be discontinued from the study or study drug for any of the following reasons: 
• Withdrawal of consent; 
• Investigator or sponsor decision that withdrawal is in the subject’s best interest; 
• Occurrence of an AE that, in the opinion of the investigator, warrants discontinuation of 
the subject from the study drug; 




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12.1 Study Treatment Groups 
Randomized subjects will receive active treatment as detailed below. For the purpose of 
maintaining treatment blinding, all randomized subjects will receive matching SCY-078 placebo 
tablets and/or matching fluconazole placebo capsules as needed based on treatment assignment, in 
a double-dummy fashion. All study drug will be self-administered by the subjects. 
Treatment Group 1 (oral SCY-078 750 mg QD on Day 1 only):  
Subjects randomized to Treatment Group 1 will receive oral SCY-078 750 mg QD on Day 1 only 
(total daily dose of 750 mg). On randomization day (Baseline [Day 1]), subjects will take 5 tablets 
of SCY-078 150 mg in the morning. Study drug must be administered 30 minutes before or 2 hours 
after any meal and must be taken with approximately 8 oz./240 mL of water. 
Treatment Group 2 (oral SCY-078 300 mg BID on Day 1 only):  
Subjects randomized to Treatment Group 2 will receive oral SCY-078 300 mg BID on Day 1 only 
(total daily dose of 600 mg). On randomization day (Baseline [Day 1]), subjects will take 2 tablets 
of SCY-078 150 mg in the morning and 2 tablets of SCY-078 150 mg in the evening, 
approximately 12 hours apart. Study drug must be administered 30 minutes before or 2 hours after 
any meal and must be taken with approximately 8 oz./240 mL of water. 
Treatment Group 3 (oral SCY-078 450 mg BID on Day 1 only):   
Subjects randomized to Treatment Group 3 will receive oral SCY-078 450 mg BID on Day 1 only 
(total daily dose of 900 mg). On randomization day (Baseline [Day 1]), subjects will take 3 tablets 
of SCY-078 150 mg in the morning and 3 tablets of SCY-078 150 mg in the evening, 
approximately 12 hours apart. Study drug must be administered 30 minutes before or 2 hours after 
any meal and must be taken with approximately 8 oz./240 mL of water. 
Treatment Group 4 (oral SCY-078 150 mg BID on Days 1 to 3):   
Subjects randomized to Treatment Group 4 will receive oral SCY-078 150 mg BID on Day 1 
through Day 3 (total daily dose of 300 mg). On randomization day (Baseline [Day 1]), subjects 
will take 1 tablet of SCY-078 150 mg in the morning and 1 tablet of SCY-078 150 mg in the 
evening, approximately 12 hours apart. Over the next 2 consecutive days (Day 2 and Day 3), 
subjects will take their dose in the morning upon arising and in the evening, approximately 12 
hours apart. Study drug must be administered 30 minutes before or 2 hours after any meal and 
must be taken with approximately 8 oz./240 mL of water. 
Treatment Group 5 (oral SCY-078 300 mg BID on Days 1-3):  
Subjects randomized to Treatment Group 5 will receive oral SCY-078 300 mg BID on Days 1-3 
(total daily dose of 600 mg). On randomization day (Baseline [Day 1]), subjects will take 2 tablets 
of SCY-078 150 mg in the morning and 2 tablets of SCY-078 150 mg in the evening, 
approximately 12 hours apart. Over the next 2 consecutive days (Day 2 and Day 3), subjects will 


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take their dose in the morning upon arising and in the evening, approximately 12 hours apart. Study 
drug must be administered 30 minutes before or 2 hours after any meal and must be taken with 
approximately 8 oz./240 mL of water. 
 
Treatment Group 6 (oral fluconazole 150 mg QD on Day 1 only):  
Subjects randomized to Treatment Group 6 will receive oral fluconazole 150 mg QD on Day 1 
only (total daily dose of 150 mg). On randomization day (Baseline [Day 1]), subjects will take 
1 capsule of fluconazole 150 mg in the morning. Study drug must be administered 30 minutes 
before or 2 hours after any meal and must be taken with approximately 8 oz./240 mL of water. 
12.2 Dietary Requirements 
For all treatment groups, oral study drug must be administered 30 minutes before or 2 hours after 
any meal and must be taken with approximately 8 oz./240 mL of water. 
Nutraceuticals and foods that are known CYP3A inhibitors, such as grapefruit juice, blood oranges 
and mulberry juice should not be consumed until the last PK sample is collected (TOC) (see 
Section 21.0 [Appendix A]). 
12.3 Study Drugs 
The randomized study drugs, SCY-078 (150-mg tablets), SCY-078 matching placebo tablets, 
fluconazole (150-mg capsules) and fluconazole matching placebo capsules, will be provided by 
the Sponsor. 
12.3.1 SCY-078 Description 
Study Drug Identifier: 
SCY-078 
Empirical Formula: 
C50H75N5O11 (citrate salt) 
Molecular Weight: 
922.18 (citrate salt) 
Physical Description: 
White to off-white solid 
Chemical Name: 
(1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-
2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-
pyridinyl)-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-
dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-
phenanthro[1,2-c]pyran-7-carboxylic acid, citrate salt] 


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Figure 2 
Chemical Structure of SCY-078 Citrate 
 
12.3.2 Formulation, Packaging and Labelling 
SCY-078 citrate drug product for oral administration will be supplied as a tablet containing 150 mg 
of SCY-078 active ingredient on a free-base basis. In addition to the active ingredient, the tablet 
formulation also contains silicified microcrystalline cellulose, crospovidone, mannitol, colloidal 
silicon dioxide, magnesium stearate (non-bovine) and butylated hydroxyanisole. 
Fluconazole study drug will be sourced commercially and will be modified (encapsulated) for the 
purpose of blinding. Fluconazole will be provided as a capsule containing 150 mg of active 
ingredient. 
Study drug supplies will be packaged in a treatment kit, a box containing bottles (active drug plus 
matching placebo), for all three study treatment days (Days 1-3).   
Bottles will contain the following active treatment:  
• Treatment Group 1: 5 tablets of SCY-078 
• Treatment Group 2: 4 tablets of SCY-078 
• Treatment Group 3: 6 tablets of SCY-078 
• Treatment Group 4: 6 tablets of SCY-078 (2 tablets each for Day 1, Day 2 and Day 3) 
• Treatment Group 5: 12 tablets of SCY-078 (4 tablets each for Day1, Day 2 and Day 3) 
• Treatment Group 6: 1 capsule of fluconazole 
For the purpose of blinding, the number and appearance of dosage units will be the same across 
all treatment groups, as follows: 
• Day 1: 5 tablets for the morning dose + 3 tablets and 1 capsule for the evening dose 


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• Day 2 and Day 3: 2 tablets for the morning dose + 2 tablets for the evening dose 
Labels on the kits and/or bottles containing study medication will include the following 
information and any other information required by applicable regulations:  
• Sponsor Name 
• Study Protocol Number 
• Place to write the subject number  
• Number of tablets/capsules count per bottle or box 
• Dosing instructions 
• Storage conditions 
• Caution Statement: "Caution:  New Drug – Limited by Federal (United States) Law to 
Investigational Use Only” 
12.3.3 Storage and Stability 
The pharmacist or appropriate designee at each clinical research site will be responsible for the 
study drug. For long-term storage at the site, study drug supplies provided in bottles must be kept 
in a secure area (e.g., locked cabinet) and stored at room temperature. 
 
12.4 Drug Accountability 
The investigator or designee will inventory and acknowledge receipt of all shipments of the study 
drug. An IWRS will be used to dispense study drugs to individual subjects.  Drug accountability 
logs will be used to maintain accurate records of receipt, dispensing, administration to each subject 
and return of drug.  A study monitor will periodically check the supplies of investigational products 
held by the site to verify accountability of all study drugs. At the conclusion of the study after final 
drug accountability has been completed by the monitor, all unused study drug and all medication 
containers will be returned to the Sponsor or destroyed on site if the site has procedures in place 
for study drug destruction. 
Drug supplies will be maintained in a secure, limited-access storage area under the recommended 
storage conditions (see Section 12.3.3). 
The study drug supplied for this study is only for use in subjects properly consented and enrolled 
under this protocol. 
This is a double-blind, double-dummy study.  All site and sponsor personnel will be blinded to 
treatment assignment, except for a member of the sponsor personnel or a sponsor representative 


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who will be involved in safety activities. A study site designee (e.g. pharmacist, study 
nurse/coordinator) will: 
• Record the treatment in the appropriate drug accountability log 
• Report and document any study medication issues such as crushed or broken tablets  
o All product quality complaints should be reported to the Sponsor 
• Collect and count the number of tablets and capsules remaining at the TOC (Day 10) visit 
(or Day 3, if applicable) 
• Review subject diary and tablet/capsule count, and record any unused or remaining drug 
in the drug accountability log and eCRF and note any discrepancies and reason for 
discrepancies 
 
12.5 Subject Compliance with Study Drug Dosing 
Treatment compliance will be reviewed at the Day 3 and TOC (Day 10) visits. PK subjects who 
have completed study drug dosing at the time of their Day 3 visit may have study drug collected 
on Day 3.  Study drug will be collected at the TOC (Day 10) visit for all other subjects. 
Subjects will be instructed to have the assigned treatment kit of study medication (including empty 
bottles) with them at these visits.  Compliance will be assessed based on remaining tablets as 
compared to what should have been taken and based on the subject diary where the subject will 
enter the details of study drug dosing (Section 14.13).  Details of treatment including any missing 
dose will be recorded on the eCRF. Sites are encouraged to contact the medical monitor or sponsor 
for concerns of compliance with the treatment regimen, especially for subjects who miss doses due 
to problems with tolerability.  
13.0 Non-Study Treatments 
13.1 Prior and Concomitant Medications 
All medications (including prescription and over-the-counter medications, supplements, and 
herbal products) taken from 28 days before Baseline (Day 1) through the TOC visit will be 
recorded on the eCRF. Only the use of antifungal medications, antibiotics for any reason or 
medications to treat an AE will be recorded after the TOC visit through the last study visit (FU).  
Start and stop dates of concomitant medications taken during antifungal therapy will be recorded 
on the eCRF. Prior and concomitant medications will be reviewed and recorded at all study visits. 


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Certain concomitant medications must be administered with caution or close monitoring as 
described in Appendix A Section 21.0. 
13.2 Prohibited Medications 
Medications specifically not permitted in the exclusion criteria (Section 11.2) include the 
following: 
• Non-study systemic or topical antifungal therapy 
• Topical vaginal corticoids 
• Vaginal contraceptives 
• Other investigational drug(s) 
• Strong CYP3A4/5 inhibitors, select moderate CYP3A4/5 inhibitors, CYP3A4/5 inducers, 
select CYP2C8 substrates and select P-gp substrates. 
See Section 21.0 (Appendix A) for the full list of prohibited medications. 
13.3 Medications to be Administered with Caution and Monitored as 
Appropriate 
The following medications must be administered with caution and must be monitored as 
appropriate: 
• Moderate CYP3A4/5 inhibitors (except for the select prohibited moderate CYP3A4/5 
inhibitors) 
• CYP3A4 substrates, including but not limited to sirolimus, tacrolimus and warfarin 
• Organic anion-transporting polypeptide 1B3 (OATP1B3) substrates 
See Section 21.0 (Appendix A) for the full list of medications to be administered with caution. 
13.4 Study Restrictions 
There are no additional study restrictions other than those described in Sections 11.2 (Exclusion 
Criteria), Section 12.2 (Dietary Requirements) and Section 13.2 (Prohibited Medications). 


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14.0 Study Procedures 
The following sections provide a description of the individual study procedures to be performed 
during the conduct of the study.  Detailed schedules of study assessments are provided in the 
Schedule of Visits and Procedures in Table 2. 
14.1 
Informed Consent 
Every study subject must provide written informed consent at Screening, prior to participating in 
any Screening evaluations or any other study activities (see Section 19.3). 
14.2 
Assignment of Subject Number 
At Screening, all subjects who have signed an ICF will receive a unique subject identification (ID) 
number, which will consist of a 4-digit subject ID number that will be composed of a 2-digit site 
number followed by a 2-digit sequentially assigned subject number starting at 01, at each site. For 
instance, the first subject from site 01 will have 0101 as her assigned subject number and the 
subsequent subject from this site will have 0102 as her assigned subject number. The first subject 
from site 02 will have 0201 as her assigned subject number and the subsequent subject from this 
site will have 0202 as her assigned subject number. The subject numbers assigned to eligible 
subjects will be recorded in the eCRF.  This number will be unique to each subject and will be 
used to identify the subject throughout the study. This number is different from the treatment bottle 
number.  
Subjects who are screen failures or who are not eligible for randomization will be recorded as such 
in the eCRF. For subjects who sign an ICF (i.e., are assigned a subject number) but are NOT 
assigned a treatment assignment number because they do not meet all of the inclusion/exclusion 
criteria, the applicable Screening visit pages of the eCRF will be completed. The criteria that were 
not met for randomization will be documented in the eCRF.  
14.3 
Inclusion and Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed at Screening and at Baseline (Day 1) to ensure 
that the subject qualifies for the trial. 
14.4 
Medical History and Demographics 
During the Screening visit, a complete medical history for the prior year will be recorded for each 
subject.  The medical history will include previous and current medical diagnoses and major 
surgical procedures. Subject demographics such as age, sex, race and ethnicity will also be 
collected. 


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14.5 
Abbreviated Physical Examination  
An abbreviated physical examination, including general appearance and an overall examination of 
body systems, will be conducted at Screening and at the TOC visit. 
14.6 
Urine Pregnancy Test  
A urine pregnancy test will be performed at Screening and at unscheduled visits (if needed) by the 
local laboratory for all subjects of childbearing potential. The pregnancy test results will be 
reviewed at Baseline (Day 1) before starting/dispensing study drug.  
14.7 
Safety Laboratory Tests  
Safety laboratory tests will be performed by a qualified central laboratory. Safety laboratory tests 
will also be performed at the Screening, TOC visit and at unscheduled visits, if needed. If indicated, 
these may be done more frequently as follow up to a laboratory abnormality. 
The following laboratory parameters will be determined: 
Hematology 
▪ White blood cell (WBC) count  
▪ Hemoglobin 
▪ Red blood cell (RBC) count  
▪ Hematocrit 
▪ Platelet count 
 
▪ Differential WBC count will include percentages for lymphocytes, monocytes, eosinophils and 
basophils, and absolute counts for neutrophils, lymphocytes, atypical lymphocytes, monocytes, 
eosinophils and basophils. 
 
Blood Chemistry 
▪ Glucose 
▪ Total creatine phosphokinase (CPK) 
▪ Albumin 
▪ Aspartate aminotransferase (AST/SGOT) 
▪ Sodium 
▪ Alanine aminotransferase (ALT/SGPT) 
▪ Potassium 
▪ Gamma glutamyl transferase (GGT) 
▪ Alkaline Phosphatase 
▪ Bilirubin (total, direct and indirect) 
▪ Creatinine 
▪ Total protein  
14.8 
Vulvovaginal Samples for Identification of Other Pathogens and 
Vaginal pH  
A vulvovaginal specimen will be obtained and assessed locally at the Screening visit to rule out 
bacterial vaginosis and Trichomonas. Testing for N. gonorrhea, Chlamydia or Herpes virus will 
also be conducted by a qualified laboratory (local or central laboratory), if clinically indicated. 
Vaginal samples will be tested for bacterial vaginosis, Trichomonas, N. gonorrhea, Chlamydia or 


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Herpes virus at unscheduled visits only if needed.  Vulvovaginal specimens will also be obtained 
at the Screening visit for local vaginal pH determination. 
Procedures for collecting and shipping vulvovaginal samples are described in the laboratory 
manual. 
14.9 
Vulvovaginal Samples for KOH and Fungal Culture 
At Screening, a vulvovaginal specimen will be obtained for direct microscopic examination with 
10% KOH. Subjects must have a positive KOH test at Screening to be randomized to one of the 
study treatment groups. The Screening KOH will be assessed at the site by the investigator or 
designee. A vaginal sample will also be obtained at Screening for fungal culture and species 
identification by the central laboratory and for susceptibility testing against SCY-078, fluconazole 
and additional antifungal agents. Central susceptibility testing will be done as per CLSI M27-A3 
guidelines. An additional vulvovaginal specimen will be collected at the TOC and FU visits for 
local KOH testing and for fungal culture by the central laboratory for treatment outcome 
assessment. In addition, susceptibility testing will be done at the central laboratory for all positive 
cultures for Candida spp. Vulvovaginal samples may also be taken at unscheduled visits, if needed. 
14.10 Rating of Vulvovaginal Signs by the Investigator Using the VSS Scale 
The investigator (or qualified designee) will perform vulvovaginal examinations to rate the 
subject´s signs of infection at the Screening, TOC and FU visits, as well as at unscheduled visits. 
Investigators will assess the signs of infection using the VSS Scale provided in Section 21.0 
[Appendix B]), a standardized, predefined scale. where each sign of the vagina and/or vulva will 
be given a numerical rating based on severity, as follows: 
• Edema: absent = 0; mild = 1; moderate = 2; severe = 3 
• Erythema: absent = 0; mild = 1; moderate = 2; severe = 3 
• Excoriation or fissures: absent = 0; mild = 1; moderate = 2; severe = 3 
Other findings will be recorded using the most relevant medical term in the abbreviated physical 
examination page of the eCRF. 
14.11 Rating of Vulvovaginal Symptoms by the Subject Using the VSS Scale 
Subjects will be asked to rate their vulvovaginal symptoms at Screening, from Day 1 through the 
TOC visit (Day 10), at the FU visit and at any unscheduled visit.  
Subjects will rate their symptoms of infection using the VSS Scale (see Appendix B), where each 
vulvovaginal symptom will be given a numerical rating based on severity, as follows: 


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• Itching: absent = 0; mild = 1; moderate = 2; severe = 3 
• Burning: absent = 0; mild = 1; moderate = 2; severe = 3 
• Irritation: absent = 0; mild = 1; moderate = 2; severe = 3 
From Day 1 through the TOC visit, subjects will rate their symptoms and record their scores on 
the VSS Scale included in their subject diaries. 
14.12 Randomization  
At Baseline (Day 1), subjects who meet all of the inclusion and none of the exclusion criteria will 
be randomized to one of the six study treatment groups. Subject randomization will be performed 
using an IWRS, which will assign a unique randomization number for each randomized subject 
corresponding to a study treatment. Only one randomization number and study drug treatment will 
be assigned to each eligible subject. 
14.13 Study Drug and Subject Diary Dispensing 
At Baseline (Day 1), subjects will be dispensed bottles containing study medication (see 
Section 12.3.2) and a subject diary that they will complete daily from Day 1 through the TOC 
(Day 10) visit. 
14.14 Study Drug Dosing 
Study drug doses will be self-administered by the subjects from Baseline (Day 1) through Day 3. 
Details of study treatment groups and dietary requirements for treatment administration are 
provided in Section 12.1 and Section 12.2, respectively. 
14.15 Subject Diary Completion 
Subjects will complete their diaries from Day 1 through the TOC visit. The subject diaries will 
include the VSS Scale so that subjects can rate their vulvovaginal symptoms. Subjects will record 
the date of study medication dosing, daily vulvovaginal symptoms, other medical concerns or 
complaints and concomitant medications used. Subjects will be instructed to return their subject 
diaries at the TOC visit (Day 10). 
After the TOC visit, subjects will not be required to complete a diary but will be instructed to call 
the site immediately if they experience new or worsening signs/symptoms or medical 
concerns/complaints. The site will also determine if any signs/symptoms or other medical 
concerns/complaints recorded on the diary should be reported as AEs. The information from the 
subject diary will be included as part of the eCRFs. 


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14.16 Treatment Compliance Evaluation and Study Drug Collection  
Treatment compliance will be reviewed by the investigator or designee at the Day 3 and TOC 
(Day 10) visits.  PK subjects who have completed study drug dosing at the time of their Day 3 visit 
may have study drug collected on Day 3.  Study drug will be collected at the TOC (Day 10) visit 
for all other subjects. (see Section 12.5 for further details). 
Subjects will be instructed to bring all bottles (including empty bottles) of study medication with 
them at these visits to assess medication compliance. Further details are available in Section 12.5. 
14.17 Subject Diary Collection and Review 
Subject diaries will be collected and reviewed at the TOC visit. 
14.18 Pharmacokinetic Sample Collection 
Blood samples for PK analysis will be drawn on Day 3 and Day 10 (±2) from the PK Subset only, 
which will consist of 10 subjects per treatment group (total of 60 subjects). On Day 3, samples 
will be collected at pre-dose (immediately before dosing) and at 2-6 hours’ post-dose of either the 
morning or evening dose. On Day 10, a single PK sample will be collected. For the PK Subset, the 
Day 10 (TOC) visit must occur as close to Day 10 as possible. This sample may be collected at 
any time of the day.  
On PK sampling days, the investigator must record the dosing times and sample collection times 
on the eCRF and on the subject’s medical record. Procedures for collecting, storing and shipping 
plasma samples for PK will be described in the PK Manual. 
14.19 Vital Signs 
Vital signs, including blood pressure (systolic and diastolic), heart rate, respiratory rate and body 
temperature will be measured at the Screening and TOC visits, as well as at unscheduled visits, if 
needed. 
14.20 Prior and Concomitant Medication Review 
All medications (including prescription and over-the-counter medications, supplements and herbal 
products) taken from 28 days before Baseline (Day1) and through the TOC visit will be recorded 
on the eCRF. Only the use of antifungal medications, antibiotics for any reason or any other 
medication to treat an AE will be recorded after the TOC visit through the last study visit (FU). 
Start and stop dates of concomitant medications taken during antifungal therapy will be recorded 
on the eCRF. Prior and concomitant medications will be reviewed and recorded at all study visits. 


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See Section 13.0 for prohibited medications, medications to be administered with caution and 
further details for non-study treatments. 
14.21 Adverse Event Monitoring 
AEs will be recorded and reviewed at all scheduled on-site and phone-contact visits, as well as at 
all unscheduled study visits, from the time the ICF is signed. See Section 16.0 for further reference. 






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16.0 Safety Assessments and Monitoring 
16.1 Definition of an Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom or disease 
temporally associated with the use of a study drug/study intervention, whether or not 
related to the study drug/study intervention. 
Any laboratory abnormality that is deemed to be clinically significant in the opinion of the 
investigator will be considered an AE and should be recorded in the eCRF, whether or not 
it is related to the study drug. 
Stable chronic conditions that are present prior to clinical trial enrollment and do not 
worsen are not considered AEs and will be accounted for in the subject’s medical history. 
The following can be considered AEs: 
• An exacerbation of a pre-existing illness 
• An increase in frequency or intensity of a pre-existing episodic event or condition 
• A condition detected or diagnosed after the initiation of treatment with study 
medication, even though it may have been present prior to the start of the study 
• Continuous persistent disease or symptoms present at Baseline that worsen after 
signing the informed consent or following the initiation of treatment with study 
medication 
The following are not considered AEs: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction or 
transfusion); the condition that leads to the procedure is an AE 
• Pre-existing disease or conditions present or detected at the start of the study that 
do not worsen 
• Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalizations for cosmetic surgery or elective surgery or social/convenience 
admissions) 


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• The disease being studied or signs or symptoms associated with the disease, unless 
more severe than expected for the subject’s condition or a worsening of the disease 
being studied 
16.2 Definition of a Serious Adverse Event 
A SAE is defined as an AE meeting one of the following outcomes: 
• Death 
• Life-threatening event 
• Inpatient hospitalization or prolongation of existing hospitalization 
• Persistent or significant disability/incapacity or substantial disruption of the ability 
to conduct normal life functions 
• Congenital anomaly or birth defect 
Any other important medical event that may not result in one of the above outcomes may 
be considered a SAE when, based upon appropriate medical judgment, the event may 
jeopardize the participant and may require medical or surgical intervention to prevent one 
of the outcomes listed above. 
A life-threatening AE is any AE that places the subject, in the view of the investigator, at 
immediate risk of death from the AE as it occurred.  It does not include an AE that, had it 
occurred in a more severe form, might have caused death. 
16.3 Events of Clinical Interest 
The following are considered events of clinical interest (ECIs) if they occur after dosing, 
and must be reported by the site when it becomes aware of the ECI: 
• 
ALT or AST > 8 x the upper limit of normal (ULN), confirmed by repeat testing 
• 
ALT or AST > 5 x ULN for more than 2 weeks if new compared to Baseline, 
confirmed by repeat testing 
• 
ALT or AST > 3 x ULN and either total bilirubin >2 x ULN or international 
normalized ratio (INR) >1.5 if new compared to Baseline, confirmed by repeat 
testing 
• ALT or AST > 3 x ULN, confirmed by repeat test, with the appearance of fatigue, 
nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (> 5%) 


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16.4 Overdose 
This refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively, which is above the maximum recommended dose 
according to the authorized product information.  
An overdose can occur if a subject has taken, accidentally or intentionally, a drug 
administered in a dose exceeding the protocol-specified dose.  An overdose must be 
reported within 24 hours of the site becoming aware of the overdose if such overdose 
occurs with an associated SAE. If an overdose occurs without an associated SAE, the 
overdose must be reported within 5 working days and documented in the subject diary and 
in the subject medical record. 
16.5 Pregnancy 
Female subjects who become pregnant should be immediately discontinued from the study 
and followed up to determine the outcome of the pregnancy.  The pregnancy must be 
reported to the Sponsor within 24 hours of the site becoming aware of the pregnancy.  If 
the pregnancy ends for any reason before the anticipated date, the investigator should notify 
the Sponsor.  At the completion of the pregnancy, the investigator will document the 
outcome of the pregnancy. If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (i.e., postpartum complication, spontaneous abortion, stillbirth, 
neonatal death or congenital anomaly), the investigator should follow the procedures for 
reporting an SAE. 
16.6 Unexpected Adverse Event 
An AE is considered “unexpected” if it is not listed in the IB or is of greater specificity or 
severity than those that have been observed with the particular study drug being tested.  For 
example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if the IB referred only to elevated hepatic enzymes or hepatitis.  Similarly, 
cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of 
greater specificity) if the IB listed only cerebral vascular accidents.  "Unexpected," as used 
in this definition, also refers to AEs that are mentioned in the IB as occurring with a class 
of drugs or as anticipated from the pharmacological properties of the drug but are not 
specifically mentioned as occurring with the particular drug under investigation. 


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16.7 Grading of Adverse Events 
The severity (or intensity) of an AE refers to the extent to which it affects the subject’s 
daily activities and will be classified by the investigator as mild, moderate or severe using 
the following criteria: 
• Mild:  Awareness of sign or symptom, but easily tolerated.  Not likely to require 
medical attention. 
• Moderate:  Discomfort enough to cause some interference with daily activity.  May 
require medical intervention. 
• Severe:  Intense enough to disrupt daily activities.  Likely requires medical 
intervention. 
Clarification of the difference in meaning between “severe” and “serious” 
The term “severe” is often used to describe the intensity (severity) of a specific event (as 
in mild, moderate or severe myocardial infarction); the event itself, however, may be of 
relatively minor medical significance (such as severe headache). This is not the same as 
“serious”, which is based on the outcome or action criteria usually associated with events 
that pose a threat to life or functioning.  Seriousness (not severity) serves as a guide for 
defining regulatory reporting obligations. 
16.8 Causality Assessment 
The investigator will assess causality (i.e., whether there is a reasonable possibility that the 
study drug caused the event) for all AEs and SAEs.  The relationship will be characterized 
using the following classification: 
• Related:  The temporal relationship of the AE with the study drug makes causality 
possible and as likely or more likely than due to another cause such as other drugs, 
a surgical intervention or an underlying disease. 
• Not related:  The temporal relationship of the AE with the study drug makes 
causality improbable and can be due to another cause such as other drugs, a surgical 
intervention or an underlying disease. 
16.9 Adverse Event Collection Timeframe 
All AEs and SAEs will be recorded from the time informed consent is obtained through 
the FU visit (end of study).   


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All AEs reported by the subject or observed by members of the clinical staff will be 
evaluated by the principal investigator (PI) or qualified designee. The PI will attempt, if 
possible, to establish a diagnosis based on presenting signs and symptoms.  The nature of 
the AE, time of onset relative to study drug administration, duration, severity, and 
relationship to treatment should be determined. Details of any corrective treatment must be 
recorded in the eCRF. The PI will determine whether any changes have occurred in 
baseline signs and symptoms. All AEs and SAEs will be collected in the eCRF. 
16.10 Serious Adverse Event Reporting Requirements 
All SAEs must be reported within 24 hours of the site becoming aware of the SAE.  Any 
event that is serious, study drug-related, and unexpected as assessed by the medical monitor 
or the Sponsor will be submitted to the regulatory authorities in accordance with national 
regulatory laws and regulations. The PI will be responsible for reporting all SAEs that 
require reporting to the local or central Institutional Review Board/Ethics Committee 
(IRB/EC) in accordance with its regulations and guidelines. 
16.11 Adverse Event and Serious Adverse Event Follow-up 
All AEs and SAEs will be followed up to resolution (the subject’s health has returned to 
her baseline status or all variables have returned to normal) or until an outcome is reached, 
stabilization occurs (the investigator does not expect any further improvement or 
worsening of the event) or the event is otherwise explained, regardless of whether the 
subject is still participating in the study. All appropriate therapeutic measures should be 
undertaken and recorded. Where appropriate, medical tests and examinations will be 
performed to document resolution of the event(s). 
16.12 Serious Adverse Event Reporting – Procedures for Investigators 
Initial Reports and Follow-Up SAE Reports:  To report an SAE, the SAE eCRF form within 
the Electronic Data Capture (EDC) system must be completed. All SAEs, whether or not 
deemed drug-related or expected, must be reported by the investigator or qualified designee 
within 24 hours of first becoming aware of the event.  The investigator/qualified designee 
will enter the required information regarding the SAE into the appropriate form, which will 
automatically result in distribution of the information to the appropriate sponsor contact 
If the EDC system is temporarily unavailable (>24 hours), the event, including the 
investigator-determined causality to study drug, should be reported via a paper back-up 
SAE form to Novella Safety Surveillance via (contact information, i.e., e-mail or fax will 
be available on the SAE form).  


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Upon return of the availability of EDC system, the SAE information must be entered into 
the EDC system as soon as possible. The SAE form within the EDC system must be 
updated within 24 hours of knowledge/receipt of SAE follow-up information. 
16.13 Procedures for Emergency Unblinding 
This is a double-blind, double-dummy study. The Investigator should only be unblinded if 
it is necessary to determine treatment of emergency. The study personnel responsible for 
the treatment assignment can provide the information necessary to unblind the investigator 
(evaluator), in case of an emergency. If the evaluator is unblinded, the reason for 
unblinding should be documented in the comment page of the eCRF.  
 
17.0 Data 
Collection, 
Study 
Monitoring 
and 
Record 
Management 
17.1 Data Collection and Reporting 
Data for this study will be collected using eCRFs. The investigator and study site staff will 
receive training regarding the completion of the eCRF. Visit-specific data should be 
entered into the eCRF and be ready for review as soon as possible, but no later than 5 days 
after each visit/time point. 
All protocol-required information collected during the study must be entered by the 
investigator or designated representative in the source documents and eCRF. All data entry, 
modification or deletion will be recorded indicating the individual subject, original value, 
the new value, the reason for change, who made the change, and when the change was 
made.  All data changes will be clearly indicated with a means to locate prior values. The 
investigator will maintain a list of individuals who are authorized to enter or correct data 
on the eCRFs. 
The investigator or designated sub-investigator, following review of the data in the eCRF, 
will confirm the validity of each subject’s data by signing the eCRF. 
17.2 Study Monitoring 
Study progress will be monitored by the Sponsor or its representative as frequently as 
necessary to ensure adequate and accurate data collection, protocol compliance, and study 
conduct in accordance with accepted regulatory requirements. The PI must make all the 


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subject data available to the monitor for review during the planned site monitoring visits. 
Arrangements for monitoring visits will be made in advance, except in emergency cases. 
17.3 Investigator Study Files 
The PI is responsible for maintaining all study-related documents in study files. The 
Sponsor will notify the PI when retention of study files is no longer necessary. The 
following documents will be kept in the study files or be readily accessible: 
• original protocol and all amendments; 
• signed agreement or protocol; 
• signed and dated study staff roles and responsibilities log; 
• copy of the current curriculum vitae of the PI and of all sub-investigators; 
• IRB/EC membership list and all IRB/EC approvals for the protocol and amendments, 
informed consent documentation and all updates, advertisements, and written 
information provided to subjects; all IRB/EC correspondence; documentation that the 
IB and subsequent revisions have been submitted to the IRB/EC; documentation that 
all SAEs and any periodic safety reports have been submitted to the IRB/EC; and 
annual IRB/EC renewals (as required); 
• updated laboratory certification and the laboratory’s normal values (covering the entire 
time interval of the study for all laboratory tests conducted during the study); 
• all confirmations of investigational drug receipt, drug accountability logs and drug 
return records; 
• a CD or DVD containing final subject eCRF data; 
• all correspondence to or from the Sponsor or its designees; 
• blank informed consent form; 
• Investigator’s Brochure; 
• subject screening log; 
• subject list (contains subject initials and/or protocol-specific subject number); 
• all subjects’ original signed informed consents; and, 
• monitoring visit log. 
17.4 Retention of Records 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application and until there are no pending or contemplated marketing 
applications, or at least 2 years have elapsed since the formal discontinuation of the clinical 
development of the investigational product.  These documents should be retained for a 
longer period, however, if required by the applicable regulatory requirements or by an 
agreement with the Sponsor. 


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The Sponsor will inform the PI/institution in writing of the need for record retention and 
will notify the PI/institution in writing when the trial-related records are no longer needed. 
An investigator who withdraws from the responsibility of maintaining study records or 
wishes to move them to a new location has the obligation to place them in safekeeping and 
to inform the Sponsor of their location. 
18.0 Analytical Plan 
All statistical processing will be performed using SAS® version 9.3 or later, unless 
otherwise stated.  All statistical tests will be two-sided and interpreted at a 5% significance 
level. The study is not powered for formal statistical comparisons. 
Descriptive statistics (i.e., mean, standard deviation, median, minimum, maximum, etc.) 
will be provided for all continuous variables; frequencies and percentages will be tabulated 
for incidence and categorical variables.  For parameters measured over time, observed 
values and changes from baseline will be described for each time point. 
All analyses will be presented by treatment group.  Unless otherwise stated, data will be 
analyzed as is with no imputation.  No adjustment for multiplicity will be employed. 
A Statistical Analysis Plan (SAP) describing all statistical analyses in detail will be 
provided as a separate document. The SAP will be finalized prior to unblinding of the study 
treatments. 
18.1 
Sample Size Determination 
This is an exploratory study and no formal sample size calculation was performed. 
Approximately 180 subjects will be enrolled and randomized in an equal allocation (at a 
1:1:1:1:1:1 ratio) to the six study treatment groups (see Table 1). Thirty subjects per group 
are estimated to be adequate to perform an initial assessment of the safety and tolerability 
as well as the potential efficacy of SCY-078 in subjects with AVVC.  
18.2 
Analysis Populations 
Intent-to-Treat (ITT) Population: All randomized subjects. 
Modified Intent-to-Treat (mITT) Population: All randomized subjects who have a 
positive KOH test and a confirmed positive mycological culture for yeast at Baseline. 
Per-Protocol (PP) Population: All mITT subjects who have completed the study drug 
treatment, who have a TOC evaluation AND who have no major protocol deviations.  


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PK Population: All randomized subjects who received study drug and provided at least 
one PK sample. 
Safety Population: All randomized subjects who received at least one dose of study drug 
and who have at least one post-Baseline evaluation. 
18.3 
Subject Disposition, Discontinuation, and Baseline Data 
Subject disposition in terms of the number and percentage of subjects enrolled by site will 
be tabulated. The number of subjects randomized, number completing the study, and 
reasons for discontinuation will be summarized by treatment group. Subject demographics 
and baseline characteristics such as age, race, ethnicity, sex, weight, height, body mass 
index, region (if applicable) and other relevant parameters will be tabulated by treatment 
group.  
Baseline is defined as the last non-missing assessment prior to the date (and time if 
appropriate) of the first dose of study drug. Change from baseline is defined as: post-
baseline value – baseline value. 
18.4 
Handling of Missing Data, Dose Adjustments, and Early 
Withdrawals 
For the efficacy analyses, subjects who do not have a TOC assessment will be assigned as 
treatment failures. For subjects who withdraw from the study early, every effort will be 
made to collect TOC visit information at the point of withdrawal. 
18.5 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the World Health Organization 
Drug Dictionary terminology. The number and percentage of subjects taking each 
medication before and after the first dose of study drug will be tabulated by treatment 
group. Medications taken and stopped prior to the first dose of study drug will be 
considered prior medications. Medications started on or before the FU visit date with 
missing stop dates or stop dates after the first dose of study drug will be considered 
concomitant medications. 


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18.6 
Pharmacokinetics 
18.6.1 Pharmacokinetic Assessments 
Blood samples to measure SCY-078 and possible metabolite plasma concentrations will be 
drawn on Day 3 and Day 10 (±3) from the PK Subset, which will consist of 10 subjects per 
treatment group (total of 60 subjects).  On Day 3, samples will be collected at pre-dose 
(immediately before dosing) and at 2-6 hours’ post-dose of either the morning or evening 
study drug dose. On Day 10, a single PK sample will be collected. For the PK Subset, the 
Day 10 (TOC) visit must occur as close to Day 10 as possible. This sample may be 
collected at any time. Blood will be collected from all six treatment groups to keep the 
treatment blinding but only samples from subjects assigned to SCY-078 will be analyzed 
for PK. 
18.6.2 Pharmacokinetic Analyses 
PK parameters will be estimated using Population PK analysis in NONMEM as detailed in 
the SAP. The PK analyses will be done using the PK Population. 
An evaluation of exposure for each dosing regimen relative to clinical cure will be 
performed.  
The concentration versus time data from the PK samples collected in this study will be 
analyzed using a Population PK (Pop PK) model to predict AUC and Cmax (as appropriate). 
A Pop PK modeling strategy is required because the sampling time points will not support 
a standalone PK analysis, and hence, the data from this study will be pooled with data from 
other oral studies to predict AUC and Cmax on Day 1 of treatment.  A stand-alone 
Population PK report will prepared to describe the analysis performed on the PK samples 
collected from this study. 
Further analysis of possible metabolites may be performed. 
18.7 
Efficacy 
18.7.1 Efficacy Assessments 
The primary efficacy endpoint of the study is the percentage of subjects with clinical cure 
(complete resolution of signs and symptoms) at the TOC visit. Secondary efficacy 
endpoints include the percentage of subjects with mycological eradication (negative fungal 
culture) at the TOC visit, the percentage of subjects with both clinical cure and mycological 
eradication at the TOC and FU visits, the percentage of subjects with continued clinical 


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response (continued absence of signs and symptoms) at the FU visit and the time to 
resolution of signs and symptoms after initiation of study drug. The percentage of subjects 
with a negative KOH test at the TOC visit, the percentage of subjects who are free of signs 
and symptoms at the FU visit, the percentage of subjects by Candida species infection at 
Baseline, the percentage of isolates susceptible to SCY-078 and fluconazole, the 
percentage of subjects with clinical cure (complete resolution of signs and symptoms) at 
TOC by Candida species and the percentage of subjects with mycological eradication 
(negative fungal culture) at TOC by Candida species will be evaluated as exploratory 
endpoints. 
 
The following treatment outcome definitions will be used for the assessment of efficacy: 
Clinical Outcome 
• Clinical cure: Complete resolution of signs and symptoms of vulvovaginal infection 
without need for further antifungal treatment. Specifically, for complete resolution, any 
sign or symptom should be absent (score = 0) by the TOC visit. 
• Clinical failure: No response to therapy or incomplete resolution of signs and 
symptoms or need for additional vulvovaginal or systemic antifungal therapy. If the 
subject receives or self-administers topical drug therapy for the treatment of 
vulvovaginal irritation/pruritus such as topical analgesic or corticosteroid after 
completing treatment with the study drug and before the TOC visit, the subject is 
considered a clinical failure. 
• Continued Clinical Response: Continued absence of signs and symptoms of 
vulvovaginal infection at the FU visit in subjects who achieved clinical cure at the TOC 
visit. 
• Free of Signs and Symptoms: Absence of signs and symptoms of vulvovaginal 
infection at the FU visit. 
• Mycological Outcome 
• Mycological eradication: A subject with negative culture (no growth) for Candida 
species.  
• Mycological persistence: A subject with a positive culture for Candida species. 
18.7.2 Efficacy Analyses 
The efficacy analyses will be conducted using the mITT (primary analysis population), ITT 
and PP populations. The efficacy parameters will be evaluated comparing each SCY-078 
treatment group (and all treatment groups combined) versus the active comparator 
(fluconazole) group. 


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The primary endpoint (clinical cure at TOC) will be analyzed using a Cochran-Mantel-
Haenszel row mean scores test. Pairwise treatment comparisons of SCY-078 vs. 
fluconazole will be performed using a Fisher’s Exact test; p-values and 95% confidence 
intervals will be presented. Subjects whose results are missing at Day 10 (TOC) will be 
imputed as failures in the analysis. A sensitivity analysis will be performed where subjects 
with missing values will be removed from the analysis. 
For continuous efficacy endpoints, the Student’s t-test will be used for pairwise treatment 
comparisons of SCY-078 vs. fluconazole; p-values and 95% confidence intervals will be 
presented for the differences between treatment groups. For categorical endpoints, Fisher’s 
Exact test will be performed, and p-values and 95% confidence intervals will be presented. 
The time to resolution of signs and symptoms after initiation of study drug will be analyzed 
using Kaplan-Meier methods. 
 
18.8 
Safety  
18.8.1 Safety Assessments 
Safety will be evaluated throughout the study, including the following parameters: AEs, 
physical examination, vital signs, safety laboratory tests and treatment discontinuations. 
Safety procedures are described in Section 14.0 and safety assessments are described in 
Section 16.0. 
18.8.2 Analyses 
Safety analyses will be conducted using the safety population. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 19.1 or higher. The incidence and severity of treatment-emergent AEs and SAEs 
and their relationship to treatment will be summarized by system organ class and preferred 
term. The percentage of subjects who discontinued study treatment and the reasons for 
discontinuation will be summarized by treatment group. 
Safety laboratory evaluations and vital signs will be summarized as observed values and 
as changes from baseline. In addition, shifts (with respect to the reference range) from 
baseline will be presented by treatment group for laboratory tests. 
 


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19.0 Ethics and Protection of Human Patients 
19.1 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, the ethical principles 
established by the Declaration of Helsinki (as amended in Fortaleza, Brazil, October 2013), 
the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines, the US Code of Federal Regulations (CFR) sections that address clinical 
research studies, applicable European Union regulations and/or other national and local 
ethical and legal requirements, as applicable. 
19.2 Institutional Review Board/Ethics Committee Review 
The PI or CRO must provide the IRB/EC with all appropriate materials, including a copy 
of the subject ICF. The study will not be initiated until the PI or CRO obtains written 
approval of the protocol and the subject ICF from the appropriate IRB/EC, and copies of 
these documents are received by the Sponsor. Appropriate reports on the progress of this 
study will be made by the PI to the IRB/EC, medical monitor, and Sponsor in accordance 
with applicable government regulations and in agreement with policy established by the 
Sponsor. 
19.3 Informed Consent  
The ICH issued guidelines to provide protection for human subjects in clinical 
investigations. The ICH Tripartite Guideline for Good Clinical Practice establishes the 
general requirements for informed consent. Each subject will be provided with oral and 
written information in a language they can understand that describes the nature and 
duration of the study. Before undergoing screening, each subject must consent in writing 
to study participation. The patient will sign and personally date the subject ICF. The person 
rendering consent will also sign and personally date the subject ICF as the person who 
obtained the consent of the subject. The original signed subject ICF will be retained with 
the study center’s records. Each subject will receive a copy of her signed subject ICF. In 
addition, the PI, or his or her designee, must document in the case history that informed 
consent was obtained before study participation.  
19.4 Future Use of Samples 
Biological samples collected during the study, including Candida spp. isolates (see 
Section 14.8 and Section 14.9) and plasma samples (see Section 14.18) may be maintained 


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in repositories for potential future use. Future research of Candida isolates may include in 
vitro susceptibility testing of new or existing antifungals or analysis of mechanisms of 
resistance. Future research of plasma samples may include analysis of in vitro diagnostics 
and/or an analysis of SCY-078 metabolites. Future research may also include studies that 
are unknown at this time. The samples will be retained as long as deemed useful for the 
specified research purposes.  All samples will be identified only by a coded number to 
maintain subject confidentiality.  Researchers requesting samples or information from the 
repository must have a research protocol approved by an Institutional Review Board/Ethics 
Committee.  Samples will only be retained for subjects that provide consent for future use. 
19.5 Subject Privacy and Subject Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records that leave the site 
will be identified only by a coded number to maintain subject privacy and confidentiality. 
All records will be kept in a locked file cabinet. All computer entry and networking 
programs will be performed with coded numbers only. Clinical information will not be 
released without written permission of the subject, except as necessary for monitoring by 
the medical monitor, IRB/EC, the Food and Drug Administration (FDA), the Sponsor or 
where required by law. All local privacy laws must be followed.   
19.6  Study Termination 
The PI, the sponsor, the FDA, and the IRB/EC each reserve the right to terminate the study 
in the interest of subjects’ safety and welfare. The sponsor reserves the right to terminate 
the study at any time for administrative reasons. 
19.7 Financial Disclosure 
The financial interests of all investigators from all participating clinical centers must be 
collected prior to study initiation and 1 year following the completion of the clinical trial. 


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20.0 References 
1. Sobel, JD. Vaginal candidosis. Lancet 2007;369:1961–71. 
2. Hurley R, De Louvois J. Candida vaginitis. Postgrad Med J 1979;55:645–47. 
3. Foxman B, Marsh JV, Gillespie B, Sobel JD. Frequency and response to vaginal 
symptoms among white and African American women: results of a random digit 
dialing survey. J Womens Health 1998;7:1167–74. 
4. Berg AO, Heidrich FE, Fihn SD, et al. Establishing the cause of genitourinary 
symptoms in women in a family practice. Comparison of clinical examination and 
comprehensive microbiology. JAMA 1984; 251:620–25. 
5. Eckert LO, Hawes SE, Stevens CE, Koutsky LA, Eschenbach DA, Holmes KK. 
Vulvovaginal candidiasis: clinical manifestations, risk factors, management 
algorithm. Obstet Gynecol 1998; 92: 757–65. 
6. Diflucan prescribing information. Pfizer. Revised November 2014.  
7. Larkin E, Hager C, Chandra J, Mukherjee PK, Retuerto M, Salem I, Long L, Isham 
N, Kovanda L, Borroto-Esoda K, Wring S, Angulo D, Ghannoum M. The Emerging 
Candida auris: Characterization of Growth Phenotype, Virulence Factors, 
Antifungal Activity, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, 
on Growth Morphology and Biofilm Formation. Antimicrob Agents Chemother. 
2017 Feb 21. 
8. Sobel JD, Management of recurrent vulvovaginal candidiasis: unresolved issues. 
Curr Infect Dis Rep. 2006 Nov;8(6):481-6. 
9. Vulvovaginal Candidiasis: Developing Drugs for Treatment – Guidance for 
Industry. FDA. Revised July 2016 
 
 
 
 


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21.0 Appendices 
Appendix A:  Prohibited Medications and Medications to be 
Administered with Caution 
Prohibited Medications 
The use of any topical vaginal corticoids and contraceptives is prohibited during the study.  
No antifungal treatment other than the study drug is allowed during the study. In addition, 
the medications listed below are also prohibited. 
 
Strong CYP3A4/5 inhibitors and CYP3A4/5 inducers 
CYP 
Strong Inhibitors 
Moderate Inhibitors 
Inducersa 
3A4/5 
Reversible inhibitorsb 
• boceprevir 
• conivaptan 
• indinavir 
• itraconazolec 
• ketoconazolec 
• lopinavir/ritonavir 
• mibefradil 
 
• nefazodone 
• nelfinavir 
• posaconazolec 
• telaprevir 
• telithromycin 
• voriconazolec 
Reversible inhibitorsb 
• fluconazolec 
• avasimibe 
• carbamazepine 
• phenytoin 
• rifampin 
• St. John’s wort 
Time-dependent 
inhibitorsa 
• clarithromycin 
• ritonavir 
• saquinavir 
 
 
a. The CYP3A4/5 inducers and strong time-dependent CYP3A4/5 inhibitors listed in this table 
are not permitted during the 14 days prior to enrollment and during study treatment. 
b. The strong and moderate reversible CYP3A4/5 inhibitors listed in this table are not permitted 
during the 48 hours prior to enrollment and during study treatment. 
c. No antifungal treatment other than the study drug is allowed during the study.  
 
 
 


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CYP2C8 substrates 
CYP 
Substrates 
2C8a 
amiodarone, amodiaquine, paclitaxel, repaglinide, montelukast, pioglitazone and 
rosiglitazone,  
a. The CYP2C8 substrates listed in this table are not permitted during the 48 hours prior to 
enrollment or during study treatment. 
 
P-glycoprotein (P-gp) substrates 
P-gp Drug Substratesa 
digoxin, colchicine 
a. The P-gp substrates listed in this table are not permitted during the 48 hours prior to 
enrollment or during study treatment 
 
Medications to be administered with Caution and Monitored as Appropriate 
CYP 
Moderate Inhibitors 
3A4/5 
Reversible inhibitorsa 
• amprenavir 
• aprepitant 
• atazanavir 
• buprenorphine 
• ciprofloxacin 
• crizotinib 
• cyclosporine 
 
• darunavir/ritonavir 
• fosamprenavir 
• imatinib 
• grapefruit juice, blood oranges, mulberry 
juice 
Time-dependent inhibitors:  
• diltiazem 
• erythromycin 
• verapamil 
 


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CYP3A4 substrates 
CYP 
Substrates 
3A4 
In vitro, SCY-078 was an inhibitor of CYP3A mediated metabolism of midazolam, but 
was only a weak inhibitor of metabolism of testosterone. The clinical significance of this 
inhibition is unknown; caution should be exercised when administering SCY-078 with 
drugs known to be CYP3A sensitive substrates with narrow therapeutic index. 
Subjects receiving sirolimus, tacrolimus or warfarin are permitted for enrollment in the 
study and these medications may be administered concomitantly with SCY-078 with 
close monitoring.  The administration of either sirolimus or tacrolimus should be offset 
by no less than 2 hours with the administration of SCY-078 At a minimum, blood levels 
of sirolimus, tacrolimus or PT/PTT/INR for subjects on warfarin should be measured 
after the first dose of SCY-078 and when the subject has received approximately 7 days 
of SCY-078 (at which time, SCY-078 concentrations will have reached steady state). 
Dosing adjustments and subsequent monitoring of sirolimus and warfarin should be 
undertaken in accordance with product prescribing information for the respective agents. 
Abbreviations: PT = prothrombin time; PTT = partial thromboplastin time; INR = international 
normalized ration 
 
OATP1B3 substrates 
OATP 
Substrate 
1B3 
In vitro, SCY-078 is an inhibitor of the OATP1B3 liver uptake transporter.  The clinical 
significance of this inhibition is unknown; however, there is a potential risk for 
increased exposure of the concomitant medications (arising from lowered hepatic 
clearance) when administering SCY-078 with drugs known to be OATP1B3 selective 
substrates. Therefore, caution should be exercised when administering SCY-078 with 
drugs known to be OATP1B3 selective substrates such as telmisartan, including 
monitoring the subject for signs of overexposure associated with the concomitant 
medications as described in the product prescribing information. 
 
Sources: 
• FDA Draft Guidance for Industry.  Drug Interaction Studies – Study Design, Data 
Analysis, and Implications for Dosing and Labeling.  2012. 
• Drug interactions in infectious disease by Stephen C. Piscitelli, Keith Rodvold (2007) 
• UCSF-FDA Transportal 
 


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Appendix B:  Vulvovaginal Signs and Symptoms Scale 
 
SIGNS: 
To be rated by the investigator during the vulvovaginal examination 
Sign 
Absent 
0 
Mild 
1 
Moderate 
2 
Severe 
3 
Edema 
 
 
 
 
Erythema  
 
 
 
 
Excoriation or 
fissures 
 
 
 
 
 
Definitions: 
Absent: none 
Mild: slight 
Moderate: definitely noticeable 
Severe: marked, intense 
 
 
SYMPTOMS: 
To be rated by the subject  
Symptom 
Absent 
0 
Mild 
1 
Moderate 
2 
Severe 
3 
Burning 
 
 
 
 
Itching 
 
 
 
 
Irritation 
 
 
 
 
 


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Definitions: 
Absent: I have no discomfort (i.e., burning, itching, irritation) 
Mild: I have some discomfort (i.e., burning, itching, irritation), but it does not bother me 
much 
Moderate: I have discomfort (i.e., burning, itching, irritation), which is annoying, but not 
enough to affect what I am doing 
Severe: I have discomfort (i.e., burning, itching, irritation), which is annoying enough to 
affect what I am doing