A Phase 1, Randomized, Double-blind, Sponsor-Open, Placebo- and Positive-Controlled Crossover Study to Investigate the Effect of Multiple Doses of Sisunatovir on QTc Interval in Healthy Adult Participants
Phase: PHASE1
Conditions: Healthy
Sponsor: Pfizer

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1
Title P a ge
A P H A S E 1, R A N D O MI Z E D, D O U B L E -B LI N D, S P O N S O R -O P E N, P L A C E B O - A N D 
P O SI TI V E - C O N T R O L L E D C R O S S O V E R S T U D Y T O I N V E S TI G A T E T H E 
E F F E C T O F M U L TI P L E D O S E S O F SI S U N A T O VI R O N Q T C I N T E R V A L I N 
H E A L T H Y A D U L T P A R TI CI P A N T S
St u d y I nter ve nti o n N u m ber :
P F - 0 7 9 2 3 5 6 8
St u d y I nter ve nti o n N a me:
Sis u nat o vir
U S I N D N u m ber:
1 4 3 4 7 9
[E u dr a C T /E U C T] N u m ber:
N A
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 2 4 1 0 1 5
P h ase:
1
S p o ns or Le g al A d dress:
Pfizer I nc.
6 6 H u ds o n B o ule var d East
Ne w Y or k, N Y 1 0 0 0 1
Brief Title: A St u d y  t o I n vesti gate t he Effects of Sis u nat o vir o n Q Tc I nter val i n Healt h y 
A d ult Partici pa nts.
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer. E xce pt as 
ot her wise a gree d t o i n writi n g, b y acce pti n g or re vie wi n g t hese d oc u me nt s, yo u a gree t o h ol d t his 
i nf or mati o n i n c o nfi de nce a n d n ot c o p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w ) or 
use it f or u na ut h orize d p ur p oses. I n t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer 
m ust be pr o m ptl y n otifie d.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2
D oc u me nt Hist or y
D oc u me nt
Versi o n D ate
A me n d me nt 1
1 Ma y 2 0 2 3
Ori gi nal pr ot oc ol
1 6 Marc h 2 0 2 3
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he
re q uest of c o u ntr y healt h a ut h orities a n d I R Bs/ E Cs a n d a n y gl o bal pr ot oc ol a d mi nistrati ve 
c ha n ge letter(s).
Pr ot oc ol A me n d me nt S u m m ar y of C h a n ges T a ble
A m e n d me nt 1 (1 M a y 2 0 2 3 )
O ver all R ati o n ale f or t he A me n d me nt: T he o verall rati o nale f or t his a me n d me nt is t o 
i nc or p orate a n d clarif y vari o us pr ot oc ol ele me nts base d u p o n F D A fee d bac k.
Secti o n # a n d N a m e
Descri pti o n of C h a n ge
Brief R ati o n ale
D oc u me nt Hist or y
Clarif y versi o n date of ori gi nal pr ot oc ol w as 
a p pr o ve d o n 1 6 Marc h 2 0 2 3
Versi o n date was n ot u p date d 
as part of a p pr o val
1 S y n o psis
U p date d Q T c F of m o xifl o xaci n at 3, 4, or 5 
h o urs o n Da y 3 , u p date d desi g n t hat i nitial 
pla n ne d d ose of 
 m g wit h clarificati o n t hat 
d ose is a dj uste d t o hi g hest feasi ble d ose t o c o ver 
hi g h cli nical e x p os ure ( u p t o  
 m g) , u p date d 
statistical met h o ds relate d t o m o xifl o xaci n. 
Res p o nse t o F D A a n d P C R U
fee d bac k
1. 3 Sc he d ule of 
Acti vities
A d de d clarificati o n n ote t hat H Bs A b will be 
teste d if H Bs A g a n d/ or H Bc A b is p ositi ve. 
Re m o ve d D a y  -1 ti me p oi nt si nce t his is d o ne 
o nce at scree ni n g. A d de d Pri or/c o nc o mita nt 
treat me nts re vie w at E T visit. A d de d c ol u m n t o 
clarif y t hat st u d y dr u g a d mi nistrati o n o n Da y 2 
occ urs at h o ur 0, n ot 1. 5 h o urs p ost -d ose.
Clarificati o n fr o m P C R U a n d 
ali g ne d wit h secti o n 1 0. 2 
f o ot n ote
2. 2. 3 N o ncli nical Safet y
U p date d safet y mar gi ns t o reflect hi g h cli nical 
e x p os ures of t hera pe utic d ose ( 2 0 0 m g)
U p date d t o c urre nt stat us of 
hi g h cli nical e x p os u re
2. 3. 1 Ris k Assess me nt
Re m o ve d ris k of C O VI D -1 9 pa n de mic
C urre nt stat us of C O VI D -1 9
pa n de mic.
3 O bjecti ves a n d 
e n d p oi nts
U p date d Q Tc F of m o xifl o xaci n at 3, 4, a n d 5 
h o urs o n Da y 3
Res p o nse t o F D A fee d bac k
4. 2 Scie ntific Rati o nale 
f or St u d y Desi g n
U p date d desi g n t hat i nitial pla n ne d d ose of  
 
m g wit h clarificati o n t hat d ose is a dj uste d t o 
Res p o nse t o F D A fee d bac k
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3
Secti o n # a n d N a m e
Descri pti o n of C h a n ge
Brief R ati o n ale
hi g hest feasi ble d ose t o c o ver hi g h cli nical 
e x p os ure ( u p t o  
 m g)
4. 2 Scie ntific Rati o nale 
f or St u d y Desi g n
A d de d state me nt a n d refe re nce t hat 
m o xifl o xaci n pea k effects o n Q Tc F are dela ye d 
w he n a d mi nistere d wit h f o o d
Res p o nse t o F D A fee d bac k
4. 2 Scie ntific Rati o nale 
f or St u d y Desi g n
Re m o ve d state me nt of hist oricall y o bser ve d at 1 
t o 4 h o urs p ost d ose
N ot rele va nt t o se nte nce a n d 
refere nce cite d
4. 3 J ustificati o n of D ose
A d de d j ustificati o n f or 
 u n der fe d 
c o n diti o ns a n d t hat f oll o wi n g re vie w of 
preli mi nar y data t his d ose ma y be i ncrease d t o 
 m g t o e ns ure c o vera ge of hi g h cli nical 
e x p os ure.
Res p o nse t o F D A fee d bac k
6. 1 St u d y I nter ve nti o n(s) 
a n d C o nc o mita nt 
T hera p y
U p date d pla n ne d d ose t o 
 m g wit h f o ot n ote 
t hat d ose ma y be a dj uste d t o hi g hest feasi ble 
d ose ( u p t o  
 m g)
U p date base d o n  
 
st u d y res ults a n d F D A 
fee d bac k
6. 2 Pre parati o n, 
Ha n dli n g, St ora ge, a n d 
Acc o u nta bilit y 
Re m o ve d refere nce t o I P M
As t his st u d y is c o n d ucte d at 
P C R U, I P ma n ual is n ot use d
6. 2. 1 Pr eparati o n a n d 
Dis pe nsi n g
Re m o ve d refere nce t o I P M
As t his st u d y is c o n d ucte d at 
P C R U, I P ma n ual is n ot use d
6. 6 D ose M o dificati o n
U p date d desi g n t hat i nitial pla n ne d d ose of  
 
m g wit h clarificati o n t hat d ose is a dj uste d t o 
hi g hest feasi ble d ose t o c o ver hi g h cli nical 
e x p os ure ( u p t o  
 m g)
Res p o nse t o F D A fee d bac k
8. 1 A d mi nistrati ve a n d 
Baseli ne Pr oce d ures
U p date d t otal bl o o d v ol u me t o 1 2 0 m L
clarificati o n
8. 5 P har mac o ki netics
U p date d W h ole bl o o d sa m ple v ol u me f or 
bl o o d/ plas ma rati o t o 2 m L
Fee d bac k fr o m Bi oa nal ytics
9. 1. 2 Assa y Se nsiti vit y
A d de d te xt t hat assa y se nsiti vit y of 
m o xifl o xaci n will be e val uate d o n Da y 3 at 3, 4 
a n d 5 h o urs p ost - dose, i ncl u di n g p ost -h oc 
a dj ust me nt a n d statistical met h o ds.
Res p o nse t o F D A fee d bac k
9. 3. 1. 2 E C G Data 
S u m maries
A d de d te xt t hat cate g orizati o n of H R, Q R S, a n d 
P R i nter vals will be descri be d i n t he S A P.
Res p o nse t o F D A fee d bac k
9. 3. 3 Sec o n dar y 
E n d p oi nts A nal ysis
U p date d statistical i nf or mati o n relate d t o assa y 
se nsiti vit y of m o xifl o xaci n will be e val uate d o n 
D a y  3 at 3, 4 a n d 5 h o urs p ost-d ose.
Res p o nse t o F D A fee d bac k
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4
Secti o n # a n d N a m e
Descri pti o n of C h a n ge
Brief R ati o n ale
1 0. 4. 2 Fe male 
Partici pa nt Re pr o d ucti ve 
I ncl usi o n Criteria
Clarifie d t hat W O C B P a gree to use 
c o ntrace pti o n f or at least 2 8 da ys after last d ose 
of st u d y i nter ve nti o n
T he n u m ber of da ys was 
pre vi o usl y o mitte d 
1 1 Refere nces
A d de d 2 ref ere nces relate d t o Q Tc F pea k dela ys 
w he n m o xifl o xaci n is a d mi nistere d u n der fe d 
c o n diti o ns
Res p o nse t o F D A fee d bac k
T A B L E O F C O N T E N T S
LI S T O F T A B L E S ...................................................................................................................1 0
1. P R O T O C O L  S U M M A R Y...................................................................................................1 1
1. 1. S y n o psis ..................................................................................................................1 1
1. 2. Sc he ma ....................................................................................................................1 8
1. 3. Sc he d ule of Acti vities .............................................................................................1 9
2. I N T R O D U C TI O N ...............................................................................................................2 3
2. 1. St u d y  Rati o nale.......................................................................................................2 3
2. 2. Bac k gr o u n d .............................................................................................................2 3
2. 2. 1. N o ncli nical P har mac ol o g y ..........................................................................2 4
2. 2. 2. N o ncli nical P har mac o ki netics a n d Meta b olis m ......................................... 2 5
2. 2. 3. N o ncli nical Safet y ...................................................................................... 2 6
2. 2. 4. Cli nical O ver vie w .......................................................................................2 7
2. 3. Be nefit/ Ris k Assess me nt .........................................................................................3 0
2. 3. 1. Ris k Assess me nt......................................................................................... 3 1
2. 3. 2. Be nefit Assess me nt .....................................................................................3 4
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................3 4
3. O BJ E C TI V E S A N D E N D P OI N T S .....................................................................................3 4
4. S T U D Y D E SI G N .................................................................................................................3 4
4. 1. O verall Desi g n .........................................................................................................3 4
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n.....................................................................3 5
4. 2. 1. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts .........................................3 7
4. 3. J ustificati o n f or D ose ..............................................................................................3 7
4. 4. E n d of St u d y  Defi niti o n ..........................................................................................3 9
5. S T U D Y P O P U L A T I ON................................ ......................................................................3 9
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5
5. 1. I ncl usi o n Criteria .....................................................................................................3 9
5. 2. E xcl usi o n Criteria ....................................................................................................4 0
5. 3. L ifest yle C o nsi derati o ns..........................................................................................4 2
5. 3. 1. C o ntrace pti o n ..............................................................................................4 2
5. 3. 2. Meals a n d Dietar y  Restricti o ns...................................................................4 3
5. 3. 3. Caffei ne, Alc o h ol, a n d T o bacc o .................................................................4 4
5. 3. 4. Acti vit y .......................................................................................................4 4
5. 4. Scree n Fail ures ........................................................................................................4 4
6. S T U D Y I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y .................................4 4
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................4 5
6. 1. 1. A d mi nistrati o n ............................................................................................4 6
6. 2. Pre parati o n, Ha n dli n g, St ora ge, a n d Acc o u nta bilit y ...............................................4 6
6. 2. 1. U p o n i de ntificati o n of a pr o d uct c o m plai nt, n otif y  t he s p o ns or wit hi n 
1 b usi ness da y  of disc o ver y. Pre parati o n a n d Dis pe nsi n g................................4 7
6. 3. Assi g n me nt t o St u d y I nter ve nti o n ...........................................................................4 7
6. 4. Bli n di n g................................ ...................................................................................4 8
6. 4. 1. Bli n di n g of Partici pa nts ..............................................................................4 8
6. 4. 2. Bli n di n g of Site Pers o n nel ..........................................................................4 8
6. 4. 3. Bli n di n g of t he S p o ns or.............................................................................. 4 8
6. 4. 4. Brea ki n g t he Bli n d ......................................................................................4 8
6. 5. St u d y  Inter ve nti o n C o m plia nce ...............................................................................4 9
6. 6. D ose M o dificati o n ...................................................................................................4 9
6. 7. C o nti n ue d Access t o St u d y  Inter ve nti o n After t he E n d of t he St u d y ......................4 9
6. 8. Treat me nt of O ver d ose................................ ............................................................4 9
6. 9. Pri or a n d C o nc o mita nt T hera p y................................ ..............................................5 0
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L ...........................................................................5 0
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n ....................................................................5 0
7. 2. Partici pa nt Disc o nti n uati o n/ Wit h dra wal Fr o m t he St u d y .......................................5 1
7. 2. 1. Wit h dra wal of C o nse nt ...............................................................................5 2
7. 3. L ost t o F oll o w - u p....................................................................................................5 2
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S................................ ...............................5 2
8. 1. A d mi nistrati ve a n d Baseli ne Pr oce d ures .................................................................5 2
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6
8. 1. 1. Baseli ne Pr oce d ures ....................................................................................5 4
8. 2. Efficac y  Assess me nts ..............................................................................................5 4
8. 3. Safet y Assess me nts .................................................................................................5 4
8. 3. 1. P h y sical E xa mi nati o ns ................................................................................5 4
8. 3. 2. Vital Si g ns ..................................................................................................5 4
8. 3. 2. 1. Bl o o d Press ure a n d P ulse Rate ..................................................5 4
8. 3. 3. Electr ocar di o gra ms..................................................................................... 5 5
8. 3. 4. Cli nical Safet y  La b orat or y Assess me nts....................................................5 7
8. 3. 5. C O VI D - 1 9 S pecific Assess me nts...............................................................5 7
8. 3. 6. Pre g na nc y  Testi n g ......................................................................................5 7
8. 4. A d verse E ve nts, Seri o us A d verse E ve nts, a n d Ot her Safet y Re p orti n g .................5 8
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y  f or C ollecti n g A E a n d S A E I nf or mati o n.......5 8
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer Safet y...............................................5 9
8. 4. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F................... 5 9
8. 4. 2. Met h o d of Detecti n g A Es a n d S A Es ..........................................................5 9
8. 4. 3. F oll o w- U p of A Es a n d S A Es ......................................................................5 9
8. 4. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................6 0
8. 4. 5. E n vir o n me ntal E x p os ure, E x p os ure D uri n g Pre g na nc y  or 
Breastfee di n g, a n d Occ u pati o nal E x p os ure .....................................................6 0
8. 4. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................6 0
8. 4. 5. 2. E x p os ure D u ri n g Breastfee di n g ................................................6 2
8. 4. 5. 3. Occ u pati o nal E x p os ure .............................................................6 3
8. 4. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................6 3
8. 4. 7. Disease -Relate d E ve nts a n d/ or Disease - Relate d O utc o mes N ot 
Q ualif yi n g as A Es or S A Es ..............................................................................6 3
8. 4. 8. A d verse E ve nts of S pecial I nterest............................................................. 6 3
8. 4. 8. 1. Lac k of Eff icac y........................................................................6 3
8. 4. 9. Me dical De vice Deficie ncies ......................................................................6 3
8. 4. 1 0. Me dicati o n Err ors .....................................................................................6 3
8. 5. P har mac o ki netics ....................................................................................................6 4
8. 6. G e netics ...................................................................................................................6 5
8. 6. 1. S pecifie d Ge netics ......................................................................................6 5
8. 7. Bi o mar kers ..............................................................................................................6 5
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7
8. 8. I m m u n o ge nicit y Assess me nts .................................................................................6 5
8. 9. Healt h Ec o n o mics ...................................................................................................6 5
9. S T A TI S TI C A L C O N SI D E R A T I O N S ................................................................................6 5
9. 1. Statistical H y p ot hesis ..............................................................................................6 6
9. 1. 1. Pri mar y  E n d p oi nt........................................................................................6 6
9. 1. 2. Assa y  Se nsiti vit y ........................................................................................6 6
9. 2. A nal y sis Sets ...........................................................................................................6 6
9. 3. Statistical A nal y ses .................................................................................................6 7
9. 3. 1. Ge neral C o nsi derati o ns ...............................................................................6 7
9. 3. 1. 1. Deri vati o n of E C G Para meters Pri or t o A nal y ses .....................6 8
9. 3. 1. 2. E C G Data S u m maries ...............................................................6 8
9. 3. 2. Pri mar y  E n d p oi nt A nal ysis .........................................................................6 9
9. 3. 3. Sec o n dar y  E n d p oi nts A nal ysis ...................................................................6 9
9. 3. 4. Safet y a nal ys es ............................................................................................7 0
9. 3. 5. E x pl orat or y  E n d p oi nts A nal ysis .................................................................7 0
9. 4. I nteri m A nal ys es .....................................................................................................7 0
9. 5. Sa m ple Size Deter mi nati o n................................ .....................................................7 0
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S................................ ..........................................................................7 2
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns...............7 2
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................7 2
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P .........................................................................7 2
1 0. 1. 2. I nf or me d C o nse nt Pr ocess ........................................................................7 3
1 0. 1. 3. Data Pr otecti o n .........................................................................................7 4
1 0. 1. 4. C o m mittees Str uct ure ...............................................................................7 4
1 0. 1. 4. 1. Data M o nit ori n g C o m mittee ...................................................7 4
1 0. 1. 5. Disse mi nati o n of Cli nical St u d y  Data ......................................................7 4
1 0. 1. 6. Data Q ualit y Ass ura nce ............................................................................7 5
1 0. 1. 7. S o urce D oc u me nts ....................................................................................7 7
1 0. 1 . 8. Use of Me dical Rec or ds............................................................................7 7
1 0. 1. 9. St u d y  a n d Site Start a n d Cl os ure ..............................................................7 8
1 0. 1. 1 0. P u blicati o n P olic y ...................................................................................7 8
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8
1 0. 1. 1 1. S p o ns or’s Me dicall y  Q ualifie d I n di vi d ual..............................................7 9
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests.................................................................8 1
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E val uati n g, F oll o w -U p, a n d Re p orti n g .....................................................................8 2
1 0. 3. 1. Defi niti o n of A E .......................................................................................8 2
1 0. 3. 2. Defi niti o n of a n S A E ................................................................................8 3
1 0. 3. 3. Rec or di n g/ Re p orti n g a n d F oll o w- U p of A Es a n d/ or S A Es D uri n g 
t he Acti ve C ollecti o n Peri o d............................................................................8 4
1 0. 3. 4. Re p orti n g of S A Es.................................................................................... 8 8
1 0. 4. A p pe n di x 4: C o ntrace pti ve a n d Barrier G ui da nce ................................................9 0
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria.................................... 9 0
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria .................................9 0
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ............................................................9 1
1 0. 4. 4. C o ntrace pti o n Met h o ds .............................................................................9 2
1 0. 5. A p pe n di x 5: Ge netics ............................................................................................9 4
1 0. 6. A p pe n di x 6: L i ver Safet y: S u g geste d Acti o ns a n d F oll o w-U p Assess me nts 
[a n d St u d y Inter ve nti o n Rec halle n ge G ui deli nes] .....................................................9 5
1 0. 7. A p pe n di x 7: Ki d ne y  Safet y: M o nit ori n g G ui deli nes ............................................9 7
1 0. 7. 1. La b orat or y  Assess me nt of C ha n ge i n Ki d ne y F u ncti o n a n d 
Detecti o n of Ki d ne y  Inj ur y ..............................................................................9 7
1 0. 7. 2. A g e-S pecific Ki d ne y  F u ncti o n Calc ulati o n Rec o m me n dati o ns...............9 7
1 0. 7. 2. 1. A d ults ( 1 8 Years a n d A b o ve) — 2 0 2 1 C K D - E PI 
E q uati o ns........................................................................................... 9 7
1 0. 7. 2. 2. A d olesce nts ( 1 2 Years t o < 1 8 Years) — C oc kcr oft -Ga ult 
F or m ula ..............................................................................................9 8
1 0. 7. 2. 3. C hil dre n ( 2 Years t o < 1 2 Years) —
Sc h wartz E q uati o n ..........9 8
1 0. 7. 2. 4. I nfa nts ( 1 M o nt h t o < 2 Years) a n d Ne o nates ( < 1 
M o nt h) — Sc h wartz E q uati o n................................ ............................9 8
1 0. 7. 3. Ki d n e y F u ncti o n Calc ulati o n T o ols..........................................................9 8
1 0. 7. 4. A d verse E ve nt Gra di n g f or Ki d ne y  Safety La b orat or y  
A b n or malities ...................................................................................................9 9
1 0. 8. A p pe n di x 8: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n .................................1 0 0
1 0. 9. A p pe n di x 9: Pr o hi bite d C o nc o mita nt Me dicati o ns T hat Ma y Res ult i n D DI .....1 0 2
1 0. 1 0. A p pe n di x 1 0: A b bre viati o ns .............................................................................1 0 5
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9
1 1. R E F E R E N C E S ................................................................................................................1 0 9
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0
LI S T O F T A B L E S
Ta ble 1.
St u d y  Sc he d ule of Assess me nt.................................................................1 9
Ta ble 2.
C o m plete d sis u nat o vir St u dies ................................................................. 2 7
Ta ble 3.
S u m mar y  of Preli mi nar y ( U na u dite d) Plas ma P K Para meters of 
Sis u nat o vir F oll o wi n g M ulti ple Oral D ose A d mi nistrati o n f or 5 
D a y s i n Healt hy Partici pa nts i n  
, C o m pare d t o Pre dicte d 
E x p os ures relati ve t o Rat N O A E L ................................ ...........................3 8
Ta ble 4.
Pr ot oc ol -Re q uire d Safet y L a b orat or y Assess me nts ................................. 8 1
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 1
1. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
Pr ot oc ol Title: A P hase 1, Ra n d o mize d , D o u ble- bli n d, S p o ns or -O pe n, Place b o - a n d 
P ositi ve -C o ntr olle d Cr oss o ver St u d y  t o I n vesti gate t he Effect of M ulti ple D ose s of
Sis u nat o vir o n Q Tc I nter val i n Healt h y A d ult Partici pa nts
Brief Title: A St u d y  t o I n vesti gate t he Effects of Sis u nat o vir o n Q Tc I nter val i n Healt hy 
A d ult Partici pa nts .
Re g ul at or y A ge nc y I de ntific ati o n N u m ber(s):
U S I N D N u m ber:
1 4 3 4 7 9
[E u dr a C T / E U C T] N u m ber:
N A
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A 
Pr ot oc ol N u m ber:
C 5 2 4 1 0 1 5
P h ase:
1
R ati o n ale :
Sis u nat o vir ( P F -0 7 9 2 3 5 6 8) is a n orall y a d mi nistere d R S V F -pr otei n i n hi bit or bei n g 
de vel o pe d t o tar get viral -h ost cell f usi o n f or t he treat me nt of a d ult a n d pe diatric patie nts wit h 
R S V. T his st u d y  is desi g ne d as a t h or o u g h Q T st u d y  ( T Q T) t o assess t he effect of sis u nat o vir
o n ti me fr o m t he be gi n ni n g of t he Q R S c o m ple x t o t he e n d of t he T wa ve o n t he
electr ocar di o gra m ( E C G), c orres p o n di n g t o electrical s yst ole ( Q T i nter val) as rec o m me n de d 
b y  t he I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) E 1 4 g ui deli ne a n d i n Q & As ( R 3).
O bjecti ves a n d E n d p oi nts :
O bjecti ves
E n d p oi nts
Pri m ar y: 
Pri m ar y:

T o e val uate t he effect o n Q T i nter val c orrecte d f or heart 
rate ( Q Tc) i nter val i n healt h y partici pa nts , of p ossi ble 
cli nical t hera pe utic c o nce ntrati o ns of sis u nat o vir 
c o m pare d wit h place b o.

Place b o -c orrecte d, b aseli ne a dj uste d Q Tc 
i nter val usi n g Fri dericia’s c orrecti o n 
met h o d ( Q Tc F) of sis u nat o vir at e x pecte d 
ma xi m u m c o nce ntrati o ns ( C ma x) at t he 
. 
Sec o n d ar y: 
Sec o n d ar y:

T o e val uate t he safet y a n d t olera bilit y at p ossi ble cli nical 
t hera pe utic c o nce ntrati o ns of sis u nat o vir, i ncl u di n g b ut 
n ot li mite d t o car di o vasc ular safet y.
A d verse e ve nt ( A E) , E C G assess me nts, vital 
si g n me as ure me nts, a n d cli nical safet y 
la b orat or y meas ure me nts.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 2
O bjecti ves
E n d p oi nts

T o deter mi ne st u d y se nsiti vit y b y c o m pari n g t he effect of 
m o xifl o xaci n 4 0 0 m g o n Q Tc i nter val wit h place b o at 
hist orical m o xifl o xaci n ti me f or ma xi m u m o bser ve d 
c o nce ntrati o n ( T ma x) of 3- 5 h o urs.

Baseli ne a dj uste d Q Tc F of m o xifl o xaci n 
a n d place b o at T ma x of 3 , 4, or 5 h o urs o n 
Da y 3 .
O ver all Desi g n :
T his is a P hase 1, m ulti ple -d ose, ra n d o mize d, 3 -treat me nt, 3-peri o d cr oss o ver, 6 -se q ue nce, 
s p o ns or-o pe n, place b o - a n d p ositi ve-c o ntr olle d st u d y t o be c o n d ucte d i n a p pr o xi matel y 4 2  
a d ult healt h y partici pa nts u n der fe d c o n diti o ns . A p pr o xi matel y  4 2 partici pa nts t hat will be 
ra n d o mize d i nt o 6 se q ue nces wit h 7 partici pa nts i n eac h se q ue nce. Partici pa nts assi g ne d t o 
treatme nt A will recei ve 
 oral d oses of sis u nat o vir a d mi nistere d  
 o ver  da y s i n a 
fe d state. Partici pa nts assi g ne d t o t reat me nt B will recei ve  oral d oses of matc hi n g place b o 
a d mi nistere d 
 o ver  da ys i n a fe d state. Partici pa nts assi g ne d t o treat me nt C will 
recei ve  oral d oses of place b o a d mi nistere d 
 f or  da ys f oll o we d b y a si n gle d ose 
of 4 0 0 m g m o xifl o xaci n o n t he m or ni n g of Da y  . Treat me nt assi g n me nts t o sis u nat o vir a n d 
place b o will be bli n de d t o t he partici pa nts , i n vesti gat or a n d cli nical researc h u nit ( C R U) staff 
(e xce pt p har mac y a n d s yste ms staff) b ut o pe n t o t he s p o ns or. M o xifl o xaci n a d mi nistrati o n o n 
D a y  will be u n bli n de d.
T he sis u nat o vir d ose selecte d will be t he hi g hest feasi ble s ufficie ntl y  t olerate d d ose. I n t his 
st u d y, a n i nitial d ose of 
 has bee n selecte d t o ac hie ve hi g h cli nical e x p os ure 
base d o n i nter p olati o n bet wee n t he  
 m g a n d  
 m g e x p os ures o bser ve d i n  
. 
T he safety a n d P K data fr o m a p pr o xi matel y  t he first 7 partici pa nts ma y  be assesse d a n d if
o bser ve d e x p os ure of 
 is l o wer t ha n pre dicte d (see Ta ble 3 ) a n d d o n ot c o ver 
t he hi g h cli nical e x p os ure, t he n t he d ose will be i ncrease d t o 
..
N u m ber of P artici p a nts:
A p pr o xi matel y  4 2 partici pa nts will be e nr olle d i n t he st u d y.
N ote: " E nr olle d" mea ns a partici pa nt's, or t heir le gall y a ut h orize d re prese ntati ve’s, a gree me nt 
t o partici pate i n a cli nical st u d y f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d
ra n d o mizati o n. A partici pa nt will be c o nsi dere d e nr olle d if t he i nf or me d c o nse nt is n ot 
wit h dra w n pri or t o partici pati n g i n a n y st u d y acti vit y . P ote ntial partici pa nts w h o are scree ne d 
f or t he p ur p ose of deter mi ni n g eli gi bilit y f or t he st u d y, b ut d o n ot partici pate i n t he st u d y, are 
n ot c o nsi dere d e nr olle d, u nless ot her wise s pecifie d b y  t he pr ot oc ol.
St u d y P o p ul ati o n :
K e y  i ncl usi o n a n d e xcl usi o n criteria are liste d bel o w:
I ncl usi o n Criteri a 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 3
Partici pa nts m ust meet t he f oll o wi n g k e y  i ncl usi o n criteria t o be eli gi ble f or e nr oll me nt i nt o 
t he st u d y:
A ge a n d Se x:
1.
Partici pa nts a ge d 1 8 t o 6 5 ye ars of a ge, i ncl usi ve, at t he ti me of si g ni n g of t he I C D.
2.
Male a n d fe male partici pa nts w h o are o vertl y healt h y as deter mi ne d b y me dical
e val uati o n i ncl u di n g me dical hist or y , p h ysical e xa mi nati o n, i ncl u di n g bl o o d press ure,
p ulse rate, sta n dar d 1 2 -lea d E C G, a n d la b orat or y tests.
Ot her I ncl usi o n Criteri a:
3.
B MI of 1 7. 5 t o 3 2 k g/ m 2; a n d a t otal b o d y  wei g ht > 5 0 k g ( 1 1 0 l b).
4.
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt.
E xcl usi o n Criteri a 
Partici pa nts wit h a n y  of t he f oll o wi n g c haracteristics/c o n diti o ns will be e xcl u de d:
Me dic al C o n diti o ns:
1.
E vi de nce or hist or y  of cli nicall y si g nifica nt he mat ol o gical, re nal, e n d ocri ne, 
p ul m o nar y , gastr oi ntesti nal, car di o vasc ular, he patic, ps y c hiatric, ne ur ol o gical, or 
aller gic disease (i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as y m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my).

Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve testi n g f or HI V, 
H Bs A g, H Bc A b, or H C V A b. He patitis B vacci nati o n is all o we d.

P ositi ve test res ult f or S A R S -C o V -2 i nfecti o n o n Da y  - 1.
2.
Part ici pa nts, w h o acc or di n g t o t he pr o d uct la bel f or m o xifl o xaci n, w o ul d be at 
i ncrease d ris k if d ose d wit h m o xifl o xaci n, i ncl u di n g b ut n ot li mite d t o partici pa nts
wit h hist or y  of myast he nia gra vis, te n di nitis/te n d o n r u pt ure , hist or y of 
h y perse nsiti vit y , aller g y, se vere a d verse dr u g reacti o n or i nt olerance t o q ui n ol o ne 
a nti bi otics, i ncl u di n g m o xifl o xaci n .
3.
Self -re p orte d hist or y or ris k fact ors f or Q T pr ol o n gati o n or t orsa des de p oi ntes (e g, 
or ga nic heart disease, c o n gesti ve heart fail ure, h y p o kale mia, h y p o ma g nesae mia, 
c o n ge nital l o n g Q T s y n dr o me, m y ocar di al isc he mia or i nfarcti o n), c o n ge nital 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 4
deaf ness, fa mil y  hist or y of car diac arrest or s u d de n deat h, a n d fa mil y hist or y of l o n g 
Q T s y n dr o me.
4.
Ot her me dical or ps y c hiatric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past year) or 
acti ve s uici dal i deati o n/ be ha vi or o r la b orat or y a b n or malit y or ot her c o n diti o ns or
sit uati o ns relate d t o C O VI D-1 9 pa n de mic t hat ma y  i ncrease t he ris k of st u d y
partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, ma ke t he partici pa nt i na p pr o priate f or
t he st u d y.
Pri or/ C o nc o mit a nt T her a p y:
5.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts
wit hi n 7 da y s or 5 half-li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y
i nter ve nti o n wit h t he e xce pti o n of a nti bi otics a n d m o derate/str o n g C Y P 3 A i n d ucers 
or ti me-de pe n de nt i n hi bit ors w hic h are pr o hi bite d wit hi n 1 4 da y s pl us 5 half-li ves 
pri or t o t he first d ose of st u d y  i nter ve nti o n.
6.
C urre nt use of a n y pr o hi bite d c o nc o mita nt me dicati o n(s) or partici pa nt 
u n willi n g/ u na ble t o use a per mitte d c o nc o mita nt me dicati o n(s). 
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
7.
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal pr o d uct ( dr u g or vacci ne) wit hi n 
3 0 da y s ( or as deter mi ne d b y t he l ocal re q uire me nt) or 5 half -li ves prece di n g t he first 
d ose of st u d y  i nter ve nti o n use d i n t his st ud y  ( w hic he ver is l o n ger).
Di a g n ostic Assess me nts:
8.
A p ositi ve uri ne dr u g test.
9.
F or fe males, pre g na nc y , as i n dicate d b y a p ositi ve ser u m pre g na nc y test at scree ni n g 
a n d/ or p ositi ve uri ne pre g na nc y  test i n W O C B P at Da y - 1.
1 0. Scree ni n g s u pi ne B P ≥1 4 0 m m H g (s ys tolic) or ≥9 0 m m H g ( diast olic), f oll o wi n g at 
least 5 mi n utes of s u pi ne rest. If B P is ≥1 4 0 m m H g (s ys t olic) or ≥9 0 m m H g 
( diast olic), t he B P s h o ul d be re peate d 2 m ore ti mes a n d t he a vera ge of t he 3 B P 
val ues s h o ul d be use d t o deter mi ne t he partici pa nt’s el i gi bilit y.
1 1. Sta n dar d 1 2 -lea d E C G t hat de m o nstrates cli nically rele va nt a b n or malities t hat ma y 
affect partici pa nt safet y or i nter pretati o n of st u d y res ults (e g, Q Tc F > 4 5 0 ms, 
c o m plete L B B B, si g ns of a n ac ute or i n deter mi nate- a ge m y o car dial i nfarcti o n, S T -T 
i nter val c ha n ges s u g gesti ve of m yocar dial isc he mia, sec o n d - or t hir d - de gree A V 
bl oc k, or seri o us bra d yarr h yt h mias or tac h ya rr hyt h mias). If t he u nc orrecte d Q T 
i nter val is > 4 5 0 ms, t his i nter val s h o ul d be rate-c orrecte d usi n g t he Fri dericia met h o d 
o nl y  a n d t he res ulti n g Q Tc F s h o ul d be use d f or decisi o n ma ki n g a n d re p orti n g. If 
Q Tc F e xcee ds 4 5 0 ms, or Q R S e xcee ds 1 2 0 ms, t he E C G s h o ul d be re peate d t wice 
a n d t he a vera ge of t he 3 Q Tc F or Q R S val ues use d t o deter mi ne t he partici pa nt’s
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 5
eli gi bilit y. Partici pa nts w it h a n a vera ge Q Tc i nter val > 4 5 0 millisec o n ds ( ms) will n ot 
be all o we d t o partici pate i n t he st u d y . C o m p uter i nter prete d - E C Gs s h o ul d be 
o verrea d b y a p h ys icia n e x perie nce d i n rea di n g E C Gs bef ore e xcl u di n g a partici pa nt.
1 2. Partici pa nts wit h A N Y of t he f oll o w i n g a b n or malities i n cli nical la b orat or y tests at
scree ni n g, as assesse d by t he st u d y -s pecific la b orat or y a n d c o nfir me d by a si n gle
re peat test, if dee me d necessar y:

G F R < 6 0 m L / mi n/ 1. 7 3 m 2 base d o n C K D-E PI e q uati o n;

A S T or A L T le vel ≥1. 5 x U L N;

Ga m ma -G T > 1. 2 x U L N;

Al kali ne p h os p hatase > 1. 2 x U L N;

T otal bilir u bi n le vel ≥1. 5 × U L N; partici pa nts wit h a hist or y of Gil bert’s 
s yn dr o me ma y  ha ve direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or t his st u d y 
pr o vi de d t he direct bilir u bi n le vel is ≤ U L N.
Ot her E xcl usi o n Criteri a:
1 3. Hist or y  of alc o h ol a b use or bi n ge dri n ki n g a n d/ or a n y ot her illicit dr u g use or 
de pe n de nce wit hi n 6 m o nt hs of Scree ni n g. Bi n ge dri n ki n g is defi ne d as a patter n of 
5 ( male) a n d 4 (fe male) or m ore alc o h olic dri n ks i n a b o ut 2 h o urs. As a g e neral r ule, 
alc o h ol i nta ke s h o ul d n ot e xcee d 1 4 u nits per wee k ( 1 u nit = 8 o u nces ( 2 4 0 m L ) beer, 
1 o u nce ( 3 0 m L ) of 4 0 % s pirit, or 3 o u nces ( 9 0 m L ) of wi ne).
1 4. Use of t o bacc o or nic oti ne-c o ntai ni n g pr o d ucts i n e xcess of t he e q ui vale nt of 5 
ci garettes/ da y or 2 c he ws of t o bacc o/ da y .
1 5. Bl o o d d o nati o n (e xcl u di n g plas ma d o nati o ns) of a p pr o xi matel y  1 pi nt ( 5 0 0 m L ) or 
m ore wit hi n 6 0 da y s pri or t o d osi n g.
1 6. U n willi n g or u na ble t o c o m pl y  wit h t he criteria i n t he Li fest yle C o nsi derati o ns
secti o n of t his pr ot oc ol.
1 7. I n vesti gat or site staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d s p o ns or a n d s p o ns or 
dele gate e m pl o y ees directl y i n v ol ve d i n t he c on d uct of t he st u d y  a n d t heir fa mil y 
me m bers.
St u d y Ar ms a n d D ur ati o n:
F or i n di vi d ual partici pa nts, t he t otal d urati o n of partici pati o n fr o m t he scree ni n g visit t o t he 
f oll o w-u p visit will be a p pr o xi matel y  14 wee ks.  Scree ni n g e val uati o n will occ ur wit hi n t he 
2 8 da y s pri or t o d osi n g i n t he first treat me nt peri o d. D uri n g eac h treat me nt peri o d, eli gi ble 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 6
partici pa nt s w h o meet t he e ntr y criteria will be a d mitte d o n Da y -1, pri or t o treat me nt 
a d mi nistrati o n o n Da y 1, a n d will resi de i n t he P C R U u ntil c o m pleti o n o f pr ot oc ol 
assess me nts o n Da y 4. Partici pa nt s ma y be disc har ge d bet wee n st u d y peri o ds at t he 
discreti o n of t he i n vesti gat or. T here will be a was h o ut of at least 7 d a y s bet wee n d ose 
a d mi nistrati o ns i n c o nsec uti ve cr oss o ver treat me nt peri o ds. F oll o w -u p c o ntact will be ma de 
at least 2 8 cale n dar da ys a n d u p t o 3 5 cale n dar da ys after t he last a d mi nistrati o n of t he 
i n vesti gati o nal pr o d uct t o ca pt ure a ny p ote ntial A Es a n d c o nc o mita nt treat me nts, a n d t o 
c o nfir m a p pr o priate c o ntrace pti o n usa ge, c o ntact wit h t he partici pa nt m a y  be d o ne via p h o ne. 
F or eac h partici pa nt, t he d urati o n of partici pati o n fr o m Peri o d 1 a d missi o n t o disc har ge will 
be a p pr o xi matel y  4 wee ks. T he f oll o w -u p call will occ ur u p t o 5 wee ks after last d ose of 
st u d y dr u g .
St u d y I nter ve n ti o n(s)
I nter ve nti o n N a me
P F - 0 7 9 2 3 5 6 8 (sis u nat o vir)
Place b o f or P F-0 7 9 2 3 5 6 8 
(sis u nat o vir)
M o xi fl o xaci n
Tre at me nt Ar m
A
B
C
U nit D ose Stre n gt h(s)
5 0 m g
Place b o
4 0 0 m g
D ose F or m ul ati o n
Ca ps ule 
Ca ps ule 
Ta blet
D os a ge Le vel(s)
Pl a n ne d d oses are 
*
m g
 f or  d oses
0 m g
 f or  
d oses
4 0 0 m g m o xifl o xaci n o n 
Da y 
* *
R o ute of A d mi nistr ati o n
Oral 
Oral
Oral
Use
E x peri me ntal
P lace b o-co m parat or
A cti ve-c o m parat or
I M P or NI M P/ A x M P
I M P
I M P
A x M P
* D ose will be a dj uste d t o t he hi g hest feasi ble d ose t hat is s ufficie nt well t olerate d , u p t o 
.
* * Sis u nat o vir place b o will be a d mi nistere d  
 f or  d oses, f oll o we d b y a si n gle d ose of 4 0 0 m g 
m o xifl o xaci n o n Da y .
St atistic al Met h o ds :
I n t his st u dy a p pr o xi matel y 4 2 partici pa nts will be e nr olle d. Statistical p o wer a nal ys es 
s u g gest t hat 4 2 partici pa nts will pr o vi de a p pr o xi matel y 9 9 % p o wer t o detect a mea n 
differe nce of 5 m sec bet wee n m o xifl o xaci n a n d place b o at 3 h o urs p ost -d ose of m o xifl o xaci n 
( hist oric p o p ulati o n Tma x ) if t he e x pecte d mea n differe nce bet wee n m o xifl o xaci n a n d place b o 
is n o less t ha n 1 0 msec at T ma x .
F or t he pri mar y  o bjecti ve, a P K/ p har mac o d y n a mic ( P D) m o del will be esta blis he d t o 
c haracterize t he relati o ns hi p bet wee n sis u nat o vir plas ma c o nce ntrati o n a n d c ha n ge fr o m 
baseli ne i n heart rate ‑c orrecte d Q T i nter val (Q Tc) i n t his st u d y . C ha n ge fr o m baseli ne i n 
Fri dericia’s heart ‑rate c orrecte d Q T i nter val (Q Tc F) will be t he defa ult de pe n de nt varia ble.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 7
T he m o del ‑ deri ve d mea n place b o‑c orrecte d c ha n ge fr o m baseli ne i n Q Tc ( Q Tc F ) a n d 
c orres p o n di n g 2 ‑si de d 9 0 % c o nfi de nce i nter vals ( CIs) will be c o m p ute d at c o nce ntrati o ns of 
i nterests, e g, e x pecte d Cma x at t he 
.  If t he u p per b o u n d of t he 2‑si de d 
9 0 % i nter val f or t he Q Tc F as esti mate d b y  t he fi nal c o nce ntrati o n‑Q Tc m o del 
esta blis he d i n t his st u d y is < 1 0 msec at t he hi g hest cli nicall y rele va nt e x p os ure, t he a bse nce 
of a n effect of sis u nat o vir o n Q Tc will be c o ncl u de d.  T he hi g hest cli nicall y  rele va nt 
e x p os ure ( d ue t o i ntri nsic a n d/ or e x tri nsic fact ors) will be deter mi ne d later fr o m ot her 
st u dies.
F or t he sec o n dar y o bjecti ve t o deter mi ne st u dy se nsiti vit y , t he c ha n ge fr o m baseli ne Q Tc F 
i nter val will be a nalyz e d usi n g a M M R M m o del wit h se q ue nce, peri o d, treat me nt, ti me ( p ost -
d ose ti me p oi nt ), a n d treat me nt b y ti me i nteracti o n as fi xe d effects, partici pa nts as ra n d o m 
effect, a n d baseli ne Q Tc F as c o variate. Esti mate s of t he mea n differe nce bet wee n 
m o xifl o xaci n a n d place b o at 3, 4, a n d 5 hrs p ost -d ose a n d t he c orres p o n di n g t w o -si de d
B o nferr o ni -a dj uste d 9 0 % CI s (9 6. 7 % CIs) will be re p orte d se parately . T his st u d y will be 
dee me d se nsiti ve t o detect Q T/ Q Tc pr ol o n gati o n if t he l o wer li mit of t he B o nferr o ni -a dj uste d 
9 0 % CI ( 9 6. 7 % CI ) of mea n differe nce bet we e n m o xifl o xaci n a n d place b o at a n y of t he 3, 4, 
or 5 hrs p ost -d ose is greater t ha n 5 m sec. 
Et hic al C o nsi der ati o ns:
T here is n o k n o w n be nefit f or healt h y partici pa nt s partici pati n g i n t his trial. T his st u d y  is 
desi g ne d pri maril y t o i n vesti gate t he effects of sis u nat o vir o n Q Tc I nter val.
Base d o n t h e data fr o m c o m plete d P hase 1 a n d 2 st u dies, t he cli nical safet y pr ofile of 
sis u nat o vir a p pears t o be acce pta ble. Sis u nat o vir will be a d mi nistere d i n t his st u d y  at d oses 
t hat were f o u n d t o be well t olerate d i n pre vi o us st u dies.
M o xifl o xaci n is a fl u or o q ui n ol o ne a nti bi otic t hat pr o d uces c o nsiste nt a n d pre dicta ble Q T 
pr ol o n gati o n a n d a si n gle d ose of 4 0 0 m g is r o uti nel y  use d as a p ositi ve c o ntr ol i n 
C o nce ntrati o n Q T/ Q Tc ( C -Q T) st u dies.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 8
1. 2. Sc he m a
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 9
1. 3. Sc he d ule of Acti vities
T he S o A ta ble pr o vi des a n o ver vie w of t he pr ot oc ol visits a n d pr oce d ures. Refer t o t he S T U D Y A S S E S S M E N T S A N D 
P R O C E D U R E S secti o n of t he pr ot oc ol f or detaile d i nf or mati o n o n eac h pr oce d ure a n d assess me nt re q uire d f or c o m plia nce wit h t he 
pr ot oc ol. 
T he i n vesti gat or ma y  sc he d ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d i n t he S o A ta ble, i n or der t o c o n d uct e val uati o ns or 
assess me nts re q uire d t o pr otect t he well -bei n g of t he partici pa nt. 
T a ble 1 .
St u d y Sc he d ule of Assess me nt
Visit I de ntifier
A b bre viati o ns use d i n t his 
ta ble ma y be f o u n d i n 
A p pe n di x 1 0 .
Scree n
Peri o d 1 t o Peri o d 3
F/ U 
C all
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 
t o 
D a y - 2
D a y 
- 1
D a y 
1
D a y 2
D a y 3
D a y 
4
3 1-
3 8
D a ys

Scree ni n g ≤2 8 da ys bef ore t he 
first d ose.

Da y relati ve t o start of st u d y 
i nter ve nti o n ( Da y 1).

W as h o ut ≥7 da ys bet wee n 
d oses
H o urs After D ose
0
1. 5
4 
5 
6
1 2
0
1. 5
3 
4 
5 
6 
8
1 2 
2 4
I nf or me d c o nse nt
X

I nf or me d c o nse nt s h o ul d be 
o btai ne d pri or t o u n der g oi n g 
a n y st u d y-s pecific pr oce d ures. 

See Secti o n 1 0. 1. 2 f or 
a d diti o nal i nf or mati o n.
C R U c o nfi ne me nt
X
 





 
 
 
 
 
 
 
 

X
I ncl usi o n/e xcl usi o n criteria
X  
X

Peri o d 1 o nl y
Me dical/ me dicati o n hist or y
X  
X
X

Peri o d 1 o nl y
Pri or/c o nc o mi ta nt treat me nts
X  
X
 





 
 
 
 
 
 
 
 
 

X  
X

Re vie w c o nc o mi ta nt treat me nts 
P h ysical e xa m
X  
X
X  
X

P E  at Scree ni n g or Peri o d 1 
Da y -1 o nl y. A brief P E at ot her 
ti mes at t he discreti o n of t he 
i n vesti gat or.

I ncl u di n g hei g ht a n d wei g ht at 
scree ni n g o nl y.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 0
T a ble 1 .
St u d y Sc he d ule of Assess me nt
Visit I de ntifier
A b bre viati o ns use d i n t his 
ta ble ma y be f o u n d i n 
A p pe n di x 1 0 .
Scree n
Peri o d 1 t o Peri o d 3
F/ U 
C all
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 
t o 
D a y - 2
D a y 
- 1
D a y 
1
D a y 2
D a y 3
D a y 
4
3 1-
3 8
D a ys

Scree ni n g ≤2 8 da ys bef ore t he 
first d ose.

Da y relati ve t o start of st u d y 
i nter ve nti o n ( Da y 1).

W as h o ut ≥7 da ys bet wee n 
d oses
H o urs After D ose
0
1. 5
4 
5 
6
1 2
0
1. 5
3 
4 
5 
6 
8
1 2 
2 4
Safet y la b orat or y
X  
X  
X
X  
X

Partici pa nts s h o ul d fast f or at 
least 4 h o urs bef ore safet y la bs 
are dra w n. 

I ncl u des uri nal ysis.
De m o gra p h y
X
Pre g na nc y test ( W O C B P o nl y)  
X  
X
X

Da y -1 pre g na nc y testi n g i n 
Peri o d 2 a n d 3 o nl y if 
partici pa nt is disc har ge d fr o m 
C R U bet wee n peri o ds.

E T pre g na nc y testi n g o nl y if 
partici pa nt wit h dra ws w hile n ot 
a d mitte d t o t he C R U.
C o ntrace pti o n c hec k 
X
X
X
X
X
F S H ( p ost -me n o pa usal w o me n 
o nl y)
X
Uri ne dr u g testi n g
X  
X

Da y -1 uri ne dr u g testi n g i n 
Peri o d 2 a n d 3 o nl y if 
partici pa nt is disc har ge d fr o m 
C R U bet wee n peri o ds.
1 2 -Lea d E C G (tri plic ate)  
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X

Refer t o Secti o n 8. 4. 4

Si n gle E C G f or Scree ni n g.

Pr e -d ose E C Gs are 3 sets of 
tri plicates a p pr o xi matel y 4 0 
mi n, 2 5 mi n, a n d 1 0 mi n 
bef ore pre -d ose meal. 

All ot her E C Gs are tri plicate.
Vital Si g ns ( B P, P R)
X
X
X
X
X
X
X
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 1
T a ble 1.
St u d y Sc he d ule of Assess me nt
Visit I de ntifier
A b bre viati o ns use d i n t his 
ta ble ma y be f o u n d i n 
A p pe n di x 1 0 .
Scree n
Peri o d 1 t o Peri o d 3
F/ U 
C all
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 
t o 
D a y - 2
D a y 
- 1
D a y 
1
D a y 2
D a y 3
D a y 
4
3 1-
3 8
D a ys

Scree ni n g ≤2 8 da ys bef ore t he 
first d ose.

Da y relati ve t o start of st u d y 
i nter ve nti o n ( Da y 1).

W as h o ut ≥7 da ys bet wee n 
d oses
H o urs After D ose
0
1. 5
4 
5 
6
1 2
0
1. 5
3 
4 
5 
6 
8
1 2 
2 4
HI V, H Bs A g, H Bs A b, 
H Bc A B, H C V A b 
X

H Bs A b will be teste d if 
H Bs A g a n d/ or H Bc A b is 
p ositi ve
C O VI D -1 9 relate d pr oce d ures
X  
X
 





 
 
 
 
 
 
 
 

X  
X

Perf or me d per l ocal 
pr oce d ures.
St u d y i nter ve nti o n 
a d mi nistrati o n
X  
X
X

F or sis u nat o vir a n d place b o: 
 o n Da y 1-2, o n Da y 
 o nl y i n t he m or ni n g d ose will 
be a d mi nistere d

F or m o xifl o xaci n: place b o  
 
 o n Da ys 1- 2, o n Da y  
o nl y i n t he m or ni n g 
m o xifl o xaci n will be 
a d mi nistere d. M o xifl o xaci n 
a d mi nistrati o n o n Da y  is 
u n bli n de d.

T he was h o ut bet wee n last d ose 
i n pre vi o us peri o d ≥7 da ys 
( Peri o ds 2 a n d 3 o nl y).

D ose d i n t he fe d state.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 2
T a ble 1 .
St u d y Sc he d ule of Assess me nt
Visit I de ntifier
A b bre viati o ns use d i n t his 
ta ble ma y be f o u n d i n 
A p pe n di x 1 0 .
Scree n
Peri o d 1 t o Peri o d 3
F/ U 
C all
E T
N otes
D a ys Rel ati ve t o D a y 1
D a y -2 8 
t o 
D a y - 2
D a y 
- 1
D a y 
1
D a y 2
D a y 3
D a y 
4
3 1-
3 8
D a ys

Scree ni n g ≤2 8 da ys bef ore t he 
first d ose.

Da y relati ve t o start of st u d y 
i nter ve nti o n ( Da y 1).

W as h o ut ≥7 da ys bet wee n 
d oses
H o urs After D ose
0
1. 5
4 
5 
6
1 2
0
1. 5
3 
4 
5 
6 
8
1 2 
2 4
P har mac o ki netic bl o o d 
sa m pli n g
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X

Ti me 0 P K sa m ple m ust be 
c ollecte d pri or t o d ose 
a d mi nistrati o n. 

Bl o o d sa m ples will be 
c ollecte d f oll o wi n g t he 0 h o ur 
a n d p ost -d ose E C G 
meas ure me nts at t he sa me 
ti me-p oi nts f or Treat me nt A, 
B, a n d C

Da y 2 P K sa m ples c ollecte d i n 
P e ri o d 1 o nl y. 
P har mac o ki netic 
micr osa m pli n g ( Tass o ® )
X  
X  
X  
X  
X

Da y 2 P K micr osa m ples 
c ollecte d i n Peri o d 1 o nl y. 
Ti me -matc he d t o P K bl o o d 
sa m pli n g
Bl o o d/ Plas ma rati o sa m pli n g
X  
X

D a y  2 w h ole bl o o d sa m ples 
c ollecte d i n Peri o d 1, 2 a n d 
3 t o ge nerate a w h ole bl o o d 
a n d a plas ma sa m ple.
C R U disc har ge 
X

Disc har ge per mitte d o n Da y 4 
i n eac h peri o d or o nl y at Da y 4 
of peri o d 3 at t he discreti o n of 
t he i n vesti gat or.
Seri o us a n d n o nseri o us A E 
m o nit ori n g
X
 
 





 
 
 
 
 
 
 
 
 

X  
X

See Secti o n 8. 5. 3 f or f oll o w-u p 
A E a n d S A E assess me nts.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 3
2. I N T R O D U C TI O N
P F -0 7 9 2 3 5 6 8 (sis u nat o vir, f or merl y R V 5 2 1) is a n orall y  a d mi nistere d R S V F-pr otei n 
i n hi bit or bei n g de vel o pe d t o tar get viral - h ost cell f usi o n f or t he treat me nt of a d ult a n d 
pe diatric patie nts wit h R S V.
2. 1. St u d y R ati o n ale 
T he p ur p ose of t he st u d y  is t o i n vesti gate t he effects of m ulti ple oral d oses of sis u nat o vir o n 
Q Tc I nter val.
2. 2. B ac k gr o u n d 
R S V, a me m ber of t he P ne u m o vir us fa mil y , is a si g nifica nt pat h o ge n of t he ver y yo u n g, 
i m m u n oc o m pr o mise d, a n d t he el derl y. R S V is u bi q uit o us a n d is k n o w n t o i nfect al m ost all 
c hil dre n b y 2 years of a ge. 1 T he cli nical ma nifestati o n of R S V i nfecti o n is t y picall y  mild 
u p per res pirat or y  tract ill ness. H o we ver, i n i nfa nts, yo u n g c hil dre n, t he i m m u n oc o m pr o mise d 
a n d t he el derl y, it ca n ca use seri o us L R TI . I nfa nts < 6 m o nt hs of a ge are at t he hi g hest ris k of 
se vere R S V i nfecti o n w hic h ca n lea d t o h os pitalizati o n, IC U a d miss i o n a n d e ve n deat h.2 ,3 ,4
T he c urre nt ma na ge me nt of R S V i nfecti o n i ncl u des a c o m bi nati o n of pre ve ntati ve a n d 
li mite d treat me nt meas ures, pri maril y c o nsisti n g of s u p p orti ve care. Ri ba viri n, a n ucle osi de 
a nal o g ue, is c urre ntl y t he o nl y  lice nse d a nti viral f or t he treat me nt of R S V i n c hil dre n 
( Viraz ole ®).5 T here is n o a p pr o ve d a nti viral f or t he treat me nt of R S V i n ot her a ge gr o u ps. 
M ost c urre nt g ui deli nes ma ke eit her n o rec o m me n dati o n or d o n ot rec o m me n d r o uti ne use of 
ri ba viri n d ue t o its wea k a nti viral ca pacit y, i n here nt t o xicit y a n d terat o ge nic p ote ntial.6 T h us, 
a place b o -c o ntr olle d desi g n is c o nsi dere d a p pr o priate f or trials of ne w a nti viral a ge nts f or t he 
treat me nt of R S V. Pali viz u ma b ( S yna gis ®) is a pr o p h y lactic m o n ocl o nal a nti b o d y t hat has 
bee n s h o w n t o p r otect i nfa nts a gai nst R S V disease a n d is use d i n s pecifie d hi g h ris k i nfa nt 
gr o u ps. Des pite t he a vaila bilit y  of t hese a ge nts, t heir li mite d use mea ns t hat treat me nt of 
R S V i nfecti o n re mai ns a n area of u n met nee d.
Sis u nat o vir is a p ote nt i n hi bit or of R S V F-pr otei n me diate d cell -t o-cell f usi o n. T he R S V F -
pr otei n is esse ntial f or t he e ntr y  of t he vir us t o t he h ost cell. Cell s urface e x pressi o n of t he F-
pr otei n als o ca uses cell -t o-cell f usi o n, lea di n g t o t he gia nt s y n c y tia c haracteristic of R S V 
i nfecti o n.
T he sis u nat o vir precli nical pr ofile, as well as t he safet y a n d t olera bilit y data fr o m t he first 
h u ma n d osi n g st u dies, pr o vi de a str o n g rati o nale f or t he cli nical de vel o p me nt of sis u nat o vir.
T his st u d y  is desi g ne d t o assess t he effect of sis u nat o vir o n ti me fr o m E C G Q wa ve t o t he 
e n d of t he T wa ve c orres p o n di n g t o electrical s ys t ole ( Q T i nter val) as rec o m me n de d b y t he 
I C H E 1 4 g ui deli ne a n d i n IC H E 1 4 Q & As ( R 3). 7 T he c o nce ntrati o n -Q T a nal y sis is defi ne d 
as t he pri mar y a nalys is i n t his st u d y a n d ser ves as t he pri mar y basis f or t he decisi o n t o 
classif y t he Q T pr ol o n gati o n ris k f or sis u nat o vir.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 4
2. 2. 1. N o ncli nic al P h ar m ac ol o g y

I n vitr o, sis u nat o vir has de m o nstrate d p ote nt i n hi biti o n of R S V F- pr otei n -me diate d 
cell-cell f usi o n, a n d of i nfecti o n b y a pa nel of R S V la b orat or y a n d cli nical is olates of 
b ot h A a n d B strai ns i n t he R S V pla q ue assa y . Sis u nat o vir treat me nt res ulte d i n a 
si g nifica nt re d ucti o n i n R S V i nfecti o n i n a h u ma n air wa y e pit helial cell m o del.

I n viv o, sis u nat o vir res ulte d i n a mar ke d re d ucti o n i n l u n g vir us titer i n a Bal b/ C 
m o use m o del of R S V i nfecti o n.

A n i n vitr o sec o n dar y p har mac ol o g y st u d y di d n ot re veal a ny si g nifica nt off -tar get-
acti vit y f or sis u nat o vir.

Refer t o t he sis u nat o vir I B f or f urt her details.

Sis u nat o vir was s h o w n t o be a n i n hi bit or of t he h E R G c ha n nel i n a G L P st u d y  (IC 5 0 
= 1. 8 µ M). S u bse q ue nt n o n- G L P st u dies ha ve s h o w n t hat sis u nat o vir is als o a n 
i n hi bit or of ot her i o n c ha n nel s u bt ypes i ncl u di n g t he calci u m c ha n nel Ca v 1. 2 (I C 5 0 = 
1 9. 8 µ M) a n d t he car dia c s o di u m c ha n nel Na v 1. 5 (I C 5 0 = 1 2. 1 µ M). It is k n o w n t hat 
acti vit y at b ot h of t hese i o n c ha n nel s u bty pes ca n p ote ntiall y  offset t he dela ye d 
re p olarizati o n of t he car diac acti o n p ote ntial t hat res ults fr o m h E R G i n hi biti o n.

Sis u nat o vir was assesse d i n a hI P S C -C M m o del ( u n pace d: i ntri nsicall y beati n g cells) 
t o deter mi ne if it w o ul d pr o d uce a n i ncrease i n A P D9 0 or y c A P D 9 0 f oll o wi n g b ot h 
ac ute ( 3 0 mi n) a n d c hr o nic ( 2 4 h) e x p os ure t o t he dr u g. T his s ys te m has bee n s h o w n 
t o be pre dicti ve of dr u g-i n d uce d i ncreases i n cli nical Q Tc, wit h t he hi g hest 
pre dicti vit y  o bser ve d usi n g t he c hr o nic 2 4 h ti me p oi nt. U n der ac ute treat me nt 
c o n diti o ns sis u nat o vir pr o d uce d a n i ncrease i n t he y c A P D 9 0 e n d p oi nt t hat w o ul d 
pre dict a 1 0 msec i ncrease i n Q Tc i n t he cli nic at a free c o nce nt rati o n of 1. 8 µ M, 5. 5 -
f ol d hi g her t ha n t he e x pecte d Hi g h Cli nical E x p os ures f or 2 0 0 m g  Q 1 2 x 5 da y s, 
res pecti vely. T he mea n res p o nse f or t he n o n -rate c orrecte d data at 3 0 mi n utes di d n ot 
reac h a t hres h ol d effect, h o we ver t he sta n dar d de viati o n of t he mea n di d reac h t he 
t hres h ol d at t he 4 µ M test c o nce ntrati o n. T his t hres h ol d c o nce ntrati o n w o ul d pre dict a 
1 0 msec i ncrease i n Q Tc i n t he cli nic at a free c o nce ntrati o n of 2. 9 µ M ( > 8. 9- f ol d t he 
Hi g h Cli nical E x p os ure of 2 0 0 m g Q 1 2 ). U n der c hr o nic treat me nt c o n dit i o ns i n t he 
ste m cell car di o my oc yt es sis u nat o vir di d n ot pr o d uce a n i ncrease i n eit her A P D 9 0 or 
yc A P D 9 0 at a n y of t he c o nce ntrati o ns teste d ( u p t o 1 0 0 µ M).

I n a d diti o n t o assessi n g sis u nat o vir i n a ste m cell m o del, i o n c ha n nel data wa s 
m o dele d ( h E R G bi n di n g, Ca v 1. 2/ Na v 1. 5 patc h cla m p) t o defi ne arr h y t h mia ris k, 
s pecifically T d P usi n g a n i n -silic o m o del. A nal ysis s u g geste d a t hres h ol d free 
e x p os ure of ≥1. 4 µ M w o ul d be ass ociate d wit h a T d P class pr o ba bilit y ris k of > 0. 5. 
T his is 4. 3- f ol d hi g her t ha n t he e x pecte d Hi g h Cli nical E x p os ures f or 2 0 0 m g.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 5
2. 2. 2. N o ncli nic al P h ar m ac o ki netics a n d Met a b olis m

I n a ni mal p har mac o ki netic st u dies sis u nat o vir s h o we d sl o w oral a bs or pti o n, 
m o derate -hi g h C L, hi g h v ol u me of distri b uti o n, a n d oral bi oa vaila bilit y  of 4 6 %, 4 2-
1 3 2 %, a n d 4 4 % i n m o use, rat, a n d d o g, res pecti vel y . 

Plas ma pr otei n bi n di n g of sis u nat o vir was l o w t o m o derate acr oss s pecies, wit h
a vera ge fracti o n u n b o u n d of 
 i n h u ma n, m o use, rat, 
d o g a n d g ui nea pi g, res pecti vel y. Re peat d osi n g st u di es i n t he rat s h o w t hat e xte nsi ve
distri b uti o n of sis u nat o vir t o t he l u n gs occ urs, res ulti n g i n hi g h l u n g t o plas ma rati o.
T his effect is greater t ha n d ose pr o p orti o nal fr o m 5 0 m g/ k g t o 1 5 0 m g/ k g .

C o nsiste nt wit h t he res ults of t he mi daz ola m D DI  st u d y ( C 5 42 1 0 0 4), i n vitr o st u dies 
i n dicate t hat C Y P 3 A 4 is t he mai n C Y P is of or m t hat meta b olizes sis u nat o vir wit h 
mi n or c o ntri b uti o n fr o m C Y Ps  
 a n d  
.

I n vitr o st u dies i n dicate a D DI ris k e xists f or 
 
. H o we ver, rati os of un b o u n d he patic i nlet c o nce ntrati o ns relati ve t o Ki 
val ues are l o w, a n d D DI ris k is c o nsi dere d u nli kel y  f or 
. 
T he p har mac o ki netics of 
 s u bstrates ma y be altere d w he n c o-
a d mi nistere d wit h sis u nat o vir, a n d t heref ore se nsiti ve 
 s u bstrates 
are pr o hi bite d i n t his pr ot oc ol ( A p pe n di x 9 ).

I n vitr o st u dies i n dicate t here is a ris k of i n hi biti o n of C Y Ps 
 
. T he D DI wit h C Y Ps 
 is pre dicte d t o be mi ni mal 
( pre dicte d less t ha n 2 5 % i ncrease i n A U C of a se nsiti ve s u bstrate) a n d D DI wit h 
 is pre dicte d t o be wea k. A D DI st u d y c o n d ucte d wit h sis u nat o vir ( 2 0 0 m g 
Q 1 2 ) a n d mi daz ola m as a se nsiti ve C Y P 3 A 4 pr o be s u bstrate ( C 5 2 4 1 0 0 4) i n dicate t hat 
sis u nat o vir is a m o derate 3 A 4 i n hi bit or. T here is als o a p ossi bilit y t hat t he 
p har mac o ki netics of  
 s u bstrates ma y  be altere d w he n c oa d mi nistere d wit h 
sis u nat o vir. Base d o n t hese fi n di n gs se nsiti ve or narr o w t hera pe utic i n de x 3 A 4 
s u bstrates a n d narr o w TI 
 s u bstrates are pr o hi bite d i n t his pr ot oc ol 
(A p pe n di x 9 ).

I n vitr o st udies i n dicate t hat sis u nat o vir is a P-g p s u bstrate; t heref ore, c o -
a d mi nistrati o n of i n hi bit ors f or t he tra ns p orter ( P -g p) ma y  res ult i n i ncrease d 
e x p os ure t o sis u nat o vir (a p pr o xi matel y 2-f ol d). A cli nical D DI st u d y ( C 5 2 4 1 0 0 4) 
i n dicate d t hat vera pa mil (a P-g p a n d C Y P 3 A 4 i n hi bit or) c oa d mi nistrati o n pr o d uce d 
a n a p pr o xi matel y 2. 5-f ol d i ncrease i n e x p os ure t o sis u nat o vir. Base d o n t hese 
fi n di n gs, str o n g a n d m o derate C Y P 3 A 4 a n d P-g p i n hi bit ors or i n d ucers are pr o hi bite d 
i n t his pr ot oc ol (A p pe n di x 9 ). 

T he maj or meta b olites pr o d uce d i n all s pecies a p peare d t o be h y dr o x yl ate d
meta b olites alt h o u g h s o me P hase 2 meta b olites were als o detecte d i n all s pecies. T he
meta b olite pr ofile i n t he rat, m o use, d o g, g ui nea pi g, a n d h u ma n were si milar wit h t he
e xce pti o n of M 4, a n a p pare nt d o u ble h y dr o x yl ati o n o nl y a p pare nt i n h u ma n at l o w
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 6
le vels. C o nfir mati o n of maj or meta b olites pr o d uce d i n h u ma ns is c urre ntl y u n der wa y 
i n a n A D M E st u d y, pe n di n g res ults of meta b olite i de ntificati o n ( C 5 2 4 1 0 0 8).
2. 2. 3. N o ncli nic al S afet y

I n t he re peat d ose t o xicit y st u dies i n a d ult ( u p t o 2 8 da ys) a n d ne o natal/j u ve nile rats 
a n d d o gs, t he M T Ds were defi ne d b y b o d y wei g ht l oss a n d re d uce d f o o d c o ns u m pti o n 
acc o m pa nie d b y a d verse cli nical o bser vati o n of var yi n g se verity. I n d o gs, t here was 
d ose -relate d i nci de nce of e mesis a n d li q ui d feces at ≥1 5 m g/ k g/ da y . T he ke y tar get
or ga n f or t o xicit y  i n a d ult a ni mals was t he he pat o biliar y sys te m, w hic h i ncl u de d b ot h 
de ge nerati ve a n d i nfla m mat or y  c ha n ges i n bile d uct, i n rats (≥6 0 m g/ k g/ da y ) a n d
d o gs ( ≥4 5 m g/ k g/ da y ). I n d o gs, t he he pat o biliar y fi n di n gs c orrelate d wit h ele vate d
plas ma le vels of A L P, A L T a n d G G T. I n a d diti o n, t he fi n di n gs o bser ve d o nl y  i n rats 
were i n ki d ne y ( de ge nerati o n/re ge nerati o n of me d ullar y t u b ules) at ≥1 2 0 m g/ k g/ da y ,
l u n g ( vasc ular de ge nerati o n/ necr osis) at 2 4 0 m g/ k g/ da y ( n o n-t olerate d d ose) a n d 
trac hea (e pit helial de ge nerati o n a n d s u be pit helial i nfla m mati o n [ pre d o mi na ntl y i n 
fe males]) at 1 2 0 m g/ k g/ da y i n 1 4 a n d/ or 2 8-d a y  st u dies. In t he 2 8 -d a y  d o g re peat 
d ose t o xicit y  st u d y, t he N O A E L was 1 5 m g/ k g/ da y c orres p o n di n g t o C ma x
of 7 2 9 
n g/ m L a n d A U C ta u of 9 5 1 0 n g. h/ m L. I n t he 2 8 -d a y  rat re peat d ose t o xicit y st u d y, t he 
N O A E L was 6 0 m g/ k g/ da y  c orres p o n di n g t o Cma x of 3 2 2 n g/ m L a n d A U C ta u of 4 7 2 5 
n g. h/ m L.

I n t he e m br yo -fetal t o xicit y st u dies i n rat ( G D 6-1 7) a n d ra b bit ( G D 6 -1 8), t here were 
n o effects o n pre g na nc y  or e m br yo- fetal de vel o p me nt. In rat, t he N O A E L f or 
mater nal t o xicit y  was 4 5 m g/ k g/ da y base d o n t he tra nsie nt i nitial b o d y wei g ht l oss 
f oll o we d by d ose -relate d decrease d b o dy wei g ht gai n at ≥4 5 m g/ k g/ da y . T he N O A E L
f or e m br yo- fetal t o xicit y i n rat was 6 0 m g/ k g/ da y, c orres p o n di n g t o sys te mic 
mater nal e x p os ure ( A U C 2 4) of 9 8 3 0 n g. h/ m L o n Da y 1 5 of gestati o n. I n ra b bit, 
mater nal t o xicit y  was li mite d t o l ower b o d y  wei g ht gai n a n d f o o d i nta ke at 4 5 
m g/ k g/ da y . T he N O A E L f or e m br yo- fetal de vel o p me nt i n ra b bit was 4 5 m g/ k g/ da y, 
c orres p o n di n g t o a s ys te mic mater nal e x p os ure ( A U C2 4) of 2 2 0 n g. h/ m L o n Da y 1 6 of 
gestati o n.

I n a nest hetize d g ui nea pi gs, t here were n o effects o n t he Q T or Q Tc ( Q Tc B a n d 
Q Tc F) i nter val at a n y d ose f oll o wi n g i ntra ve n o us a d mi nistrati o n (s uccessi ve d ose of 
1, 3, a n d 1 0 m g/ k g). At t he hi g hest d ose, w here pea k e x p os ure t o free sis u nat o vir w as
a p pr o xi matel y 7 3 5 n g/ m L ( ~4. 7 -f ol d t he Hi g h Cli nical E x p os ure of 2 0 0 m g Q 1 2 x 5 
da y s), a sli g ht re d ucti o n i n H R t o get her wit h ele vate d arterial bl o o d press ure, L V S P, 
L V + d P/ dt ma x (a n d  d P/ dt ma x), R R, P R a n d Q R S i nter val were o bser ve d c o m pare d 
t o ve hicle.

I n c o nsci o us tele metere d d o gs, oral d oses of sis u nat o vir u p t o 1 2 0 m g/ k g were 
e val uate d f or effects o n B P, H R, lea d II E C G ( P Q, Q T, Q Tc i nter val [ Q Tc B a n d 
Q Tc V], Q R S d urati o n, a n d E C G wa vef or m m or p h ol o g y ), a n d b o d y te m perat ure. 
C ha n ges i n car di o vasc ular pa ra meters were li mite d t o a tra nsie nt i ncrease i n H R 
n ote d fr o m 1 2 t o 1 6 h o urs p ost d ose at ≥4 5 m g/ k g wit h n o c o nc o mita nt c ha n ges i n Q T 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 7
or Q Tc i nter val a n d a sli g ht i ncrease i n diast olic arterial press ure o bser ve d u p t o 1 2 
h o urs p ost d ose at ≥4 5 m g/ k g. At 1 2 0 m g / k g, decreases i n P Q i nter val were o bser ve d 
at 2 h o urs p ost d ose i n t he a bse nce of n oticea ble c ha n ges i n a n y ot her E C G para meter. 
T hese val ues re mai ne d wit hi n t he n or mal ra n ge i n c o nsci o us d o gs. E x p os ure 
esti mates are base d o n a n ot her st u d y , i n w hic h a si n gle d ose of 1 2 0 m g/ k g i n male 
d o gs ha d a free C ma x of a p pr o xi matel y  4 8 9 n g/ m L ( ~3. 1- f ol d t he Hi g h Cli nical 
E x p os ure of 2 0 0 m g Q 1 2 x 5 da y s).

J u ve nile d o gs d ose d u p 4 5 m g/ k g Q D f or 3 wee ks s h o we d n o effects o n 
car di o vasc ular para meters ( free C ma x of 3 9 9 n g/ m L ). D o gs d ose d u p t o 1 2 0 m g/ k g Q D 
f or 1 4 d a y s s h o we d n o effects o n car di o vasc ular para meters (free C ma x of 7 0 7 n g/ m L ; 
~ 4. 5- f ol d t he Hi g h Cli nical E x p os ure of 2 0 0 m g Q 1 2 x 5 da y s). D o gs d ose d u p t o 1 5 
m g/ k g Q D f or 2 8 da y s s h o we d n o test article relate d effects o n E C G para meters. At 
4 5 m g/ k g/ da y  decreases i n gr o u p mea n H R a n d i ncreases i n R R, P R, Q T, a n d Q Tc V 
i nter val were n ote d, alt h o u g h i n di vi d ual val ues were wit hi n t he n or mal ra n ge f or 
a ni mals of t his a ge. It s h o ul d be n ote d t hat t he o bser ve d i ncrease i n Q Tc V i nter val i n 
fe males was li kel y d ue t o a n ota ble i ncrease of a p pr o xi matel y  2 0-3 0 msec fr o m 
pre d ose i n t w o fe males.
2. 2. 4. Cli nic al O ver vie w
T a ble 2.
C o m plete d sis u n at o vir St u dies
St u d y N u m ber
( St at us)
St u d y T y pe / Ke y 
Desi g n Fe at ures
St u d y P o p ul ati o n 
D ose, D osi n g 
Re gi m e n
F o r m u l ati o n 
Use d
C 5 2 4 1 0 0 1
( pre vi o usl y 
R E V C 0 0 1 a)
(c o m plete d)
P hase 1, 
ra n d o mise d, 
d o u ble -bli n d, 
place b o -
c o ntr olle d, safet y, 
t olera bilit y, P K, 
f o o d-effect of 
S A D a n d M A D
Healt h y 
partici pa nts
D ose ra n ge: 1 0 m g 
–
 m g ( S A D); 
3 6 partici pa nts
D ose ra n ge: 1 7 5 
m g –
 mg; Q 1 2
( M A D), F o o d 
effect; 2 4 
partici pa nts
Li q ui d 
F or m ulati o n
DI C
C 5 2 4 1 0 0 2
( pre vi o usl y 
R E V C 0 0 2)
(c o m plete d)
P hase 2a, 
ra n d o mise d, 
d o u ble -bli n d, 
place b o -c o ntr olle d
Healt h y 
partici pa nts 
i n oc ulate d wit h 
R S V C V
2 0 0 m g or 3 5 0 m g 
Q 1 2 f or a t otal 1 0 
d oses; 6 6 
Partici pa nts 
DI C 
C 5 2 4 1 0 0 4
( pre vi o usl y 
R E V C 0 0 4)
(c o m plete d)
P hase 1, a da pti ve, 
part ra n d o mise d, 
part o pe n -la bel, 
dr u g i nteracti o ns, 
safet y, t olera bilit y 
Healt h y 
partici pa nts 
2 0 0 m g; Q 1 2 ; 6 2 
Partici pa nts
DI C
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 8
T a ble 2 .
C o m plete d sis u n at o vir St u dies
St u d y N u m ber
( St at us)
St u d y T y pe / Ke y 
Desi g n Fe at ures
St u d y P o p ul ati o n 
D ose, D osi n g 
Re gi m e n
F o r m u l ati o n 
Use d
C 5 2 4 1 0 0 5
( pre vi o usl y 
R E V C 0 0 5) 
(c o m plete d) 
P hase 1, o pe n -
la bel, si n gle-d ose, 
P K, safet y, a n d 
t olera bilit y st u d y
Healt h y 
partici pa nts
2 0 0 m g, 4 si n gle 
d oses t otal; 9 
Partici pa nts
1 ×: DI C (fe d) 
1 ×: D P B 
dis perse d i n H 2 O 
(fe d)
1 ×: D P B 
dis perse d i n H 2 O 
(faste d)
[ was h -o ut: 3 da ys 
bet w ee n eac h of 
t he 3 d osi n g da ys] 
DI C
D P B
a. A t otal of 8 partici pa nts recei ve d t he li q ui d d osa ge f or m ulati o n of sis u nat o vir i n a s ol uti o n, at a 
c o nce ntrati o n of 5 m g/ m L, c o ntai ni n g h y dr o x y pr o p yl - β-c ycl o de xtri n ( H B P c ycl o de xtri n), L ycasi n, 
fla v ori n g a ge nt (stra w berr y), be nz oic aci d a n d water) a n d 6 8 partici pa nt s recei ve d DI C i n t he st u d y.
A t otal of 2 0 1 a d ult healt h y  partici pa nts ha ve recei ve d sis u nat o vir i n 4 c o m plete d cli nical 
st u dies ( C 5 2 4 1 0 0 1, C 5 2 4 1 0 0 2, C 5 2 4 1 0 0 4 a n d C 5 2 4 1 0 0 5) i n vesti gati n g t he P K pr ofile, 
effects of f o o d o n P K, effects of f or m ulati o n o n P K ( C 5 2 4 1 0 0 1, C 5 2 4 1 0 0 5), D DIs 
( C 5 2 4 1 0 0 4), a n d t he efficac y i n a n R S V Viral C halle n ge St u d y ( C 5 2 4 1 0 0 2) at d oses ra n gi n g 
fr o m 1 0 m g t o 5 2 5 m g. I n a d diti o n, as of 0 3 Oct o ber 2 0 2 2 , 4 5 pe diatric patie nts h os pitalize d 
d ue t o R S V L R TI ha ve bee n e nr olle d i nt o t he o n g oi n g C 5 2 4 1 0 0 3 st u d y .
T he a d mi nistrati o n of sis u nat o vir was well t olerate d at all d oses, d osa ge f or ms a n d d osi n g 
re gi me ns teste d. I n t he a d ult healt h y partici pa nts treate d t o date, t he occ urre nce of T E A Es 
c o nsi dere d relate d t o sis u nat o vir has bee n l o w. M ost c o m m o nl y  re p orte d treat me nt-relate d
T E A Es were i n t he GI dis or ders S O C; na usea, diarr hea a n d a b d o mi nal pai n. T hese T E A Es 
ha ve bee n mil d t o m o derate i n i nte nsit y  a n d res ol ve d wit h o ut se q uelae. M ost e ve nts 
attri b ute d t o IM P i n v ol ve d t he gastr oi ntesti nal tract wit h na usea, diarr hea, a n d a b d o mi nal 
pai n/ disc o mf ort/ diste nsi o n bei n g t he m ost c o m m o n a n d oc c urri n g m ore c o m m o nl y wit h t he 
3 5 0 m g d ose of sis u nat o vir t ha n wit h t he 2 0 0 m g sis u nat o vir d ose, w here t he n u m ber of 
partici pa nts re p orti n g t hese e ve nts were l o wer or si milar t o t h ose o n place b o. In c hil dre n, 
sis u nat o vir is re q uire d t o be s us pe n de d i n a s ol uti o n t o e na ble oral a d mi nistrati o n, t here has 
bee n e vi de nce of p o or t olera bilit y  w he n sis u nat o vir was s us pe n de d i n water as a si n gle d ose 
of 2. 0 m g/ k g i n c hil dre n a ge d 6 -3 6 m o nt hs, res ulti n g i n e x p ulsi o n of t he oral d ose. 
S us pe nsi o n i n breast mil k, f o r m ula mil k or sali ne a p peare d t o i m pr o ve t he palata bilit y, wit h 
all d oses bei n g s uccessf ull y a d mi nistere d t o c hil dre n a ge d 1 t o 3 6 m o nt hs i n o n g oi n g st u d y 
C 5 2 4 1 0 0 3.
As of 2 8 Oct o ber 2 0 2 2, t here ha ve bee n n o S A Es attri b uta ble t o sis u nat o vir a n d n o deat hs i n
t he cli nical st u dies.
I n a d ults, u n der b ot h fasti n g a n d fe d c o n diti o ns sis u nat o vir is sl o wl y a bs or be d reac hi n g 
ma xi m u m plas ma c o nce ntrati o ns (t ma x ) at 5- 6 h o urs ( hrs) wit h a relati vely m o derate 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 2 9
cleara nce, res ulti n g i n a half -life of 7-1 0 h o urs i n healt h y  partici pa nts. D osi n g t o stea d y  state 
res ulte d i n stea dy state c o nce ntrati o ns bei n g reac he d after a p pr o xi matel y 2 da ys of d osi n g 
res ulti n g i n 2-4 f ol d acc u m ulati o n of e x p os ure. A U C a n d C ma x val ues i ncrease d i n a greater 
t ha n d ose pr o p orti o nal ma n ner acr oss si n gle a n d m ulti ple d ose st u dies. F oll o wi n g 5 da ys of 
d osi n g, t he varia bilit y  i n P K para meters was hi g h, wit h % C V ra n gi n g fr o m 6 7. 4-8 4 % f or 
C ma x a n d 7 1. 9 -1 4 4 % f or A U C 1 2.
T he effect of f o o d o n t he si n gle d ose p har mac o ki netics was assesse d f or t he DI C a n d D P B 
dis perse d i n water. F or t he DI C t he e xte nt of s y ste mic e x p os ure t o sis u nat o vir ( ge o metric 
mea n A U C i nf u n der fe d a n d faste d c o n diti o ns) was 3 5 7 a n d 2 2 1 n g. h/ m L res pecti vel y , wit h 
t he bet wee n-s u bject varia bilit y bei n g l o wer u n der fe d c o n diti o ns ( C V 6 4. 1 % c o m pare d wit h 
1 9 8 %). T he rati o of fe d/faste d was 2 1 8 % ( 9 0 % CI 9 4. 2 - 5 0 2 %) f or C ma x a n d 1 6 2 % ( 9 0 % CI 
8 3. 0 – 3 1 6 %) f or A U C 0- i nf. It s h o ul d be n ote d t hat t he DIC faste d res ults fr o m C 5 2 4 1 0 0 1 
were l o wer t ha n t y picall y see n i n ot her st u dies wit h 2 0 0 m g a d mi nistere d u n der fasti n g 
c o n diti o ns, res ulti n g i n a n artificiall y hi g her rati o of fe d/faste d i n t his st u d y. F or t he D P B 
dis perse d i n water t he e xte nt of s y ste mic e x p os ure t o sis u nat o vir ( ge o metric mea n A U C0- i nf) 
u n der fe d a n d faste d c o n diti o ns was 3 7 1 a n d 3 3 7 n g. h/ m L res pecti vel y, wit h t he bet wee n -
s u bject varia bilit y bei n g sli g htl y l o wer u n der faste d c o n diti o ns ( C V 4 9. 0 % c o m pare d wit h 
6 1. 6 %). T he rati o of fe d/faste d was 1 0 7. 7 % ( 9 0 % CI  7 8. 0 – 1 4 8. 8 %) f or C ma x a n d 1 1 0. 0 % 
( 9 0 % CI 8 5. 6 – 1 4 1. 4 %) f or A U C 0- i nf.
Cli nical D DI  St u d y C 5 2 4 1 0 0 4 de m o nstrate d t hat t he dis p ositi o n of sis u nat o vir is e x pecte d t o
be affecte d b y m o derate t o str o n g i n hi bit ors a n d i n d ucers of C Y P 3 A 4. F urt her m ore,
sis u nat o vir was de m o nstrate d t o be a m o derate i n hi bit or of C Y P 3 A 4, s o d ose a dj ust me nts 
f or c o m p o u n ds t hat are se nsiti ve s u bstrates f or C Y P 3 A 4 ma y nee d t o be c o nsi dere d.
I n a n R S V c halle n ge st u d y, sis u nat o vir treat me nt res ulte d i n a statisticall y si g nifica nt
re d ucti o n i n A U C of R S V viral l oa d c o m pare d wit h place b o; 5 5. 2 5 % ( p = 0. 0 0 7) a n d 6 3. 0 5 % 
( p = 0. 0 0 2) f or t he 2 0 0 m g a n d 3 5 0 m g sis u nat o vir d ose gr o u ps res pecti vel y ( d ose d Q 1 2 
h o urs f or 5 da y s). Res ults f or t he A U C of t otal sy m pt o m sc ore were c o nsiste nt wit h t he viral 
l oa d A U C. Ge o metric mea n A U Cs of t otal sy m pt o m sc ore were 1 9 5. 5 6, 3 0. 7 9 a n d 3 1. 7 6 
h o urs f or place b o, 2 0 0 m g sis u nat o vir a n d 3 5 0 m g sis u nat o vir, res pecti vel y. T he re d ucti o n i n 
A U Cs of t otal s y m pt o m sc ore c o m pare d wit h place b o was statisticall y  si g nifica nt f or b ot h 
sis u nat o vir treat me nt gr o u ps; p = 0. 0 0 9 ( 8 4. 2 6%) a n d p = 0. 0 0 2 ( 8 3. 7 6 %), ( Wilc o x o n Ra n k -
S u m test) f or t he 2 0 0 m g a n d 3 5 0 m g sis u nat o vir d ose gr o u ps, re s pecti vely.
N o si g nifica nt Q Tc pr ol o n gati o n was detecte d i n C -Q T a nal ys es perf or me d i n S A D 
partici pa nts ( C 5 2 4 1 0 0 1), M A D partici pa nts ( C 5 2 4 1 0 0 1), or D DI st u d y partici pa nts 
( C 5 2 4 1 0 0 4).
S A D p orti o n of C 5 2 4 1 0 0 1: O verall, t he m o deli n g pre dicti o ns s u g gest a s h or te ni n g of Q Tc F 
wit h i ncrease d d ose, if a n y effect at all. T his is s u p p orte d b y  t he “ b y ti me p oi nt” a nalys is t hat 
d oes n ot s h o w a n y d ose relate d effects. T his st u d y di d n ot i ncl u de a place b o gr o u p, b ut si nce 
t he l o west d ose ( 1 0 m g ) res ulte d i n e x p os ure bel o w t he li mit of detecti o n, t he data fr o m t his 
gr o u p was use d as a s urr o gate f or place b o. 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 0
M A D p orti o n of C 5 2 4 1 0 0 1: T he res ults s h o w n o i n dicati o n t hat R V 5 2 1 pr ol o n gs t he Q T 
i nter val – t he sl o pe f or t he c o nce ntrati o n effect f or R V 5 2 1 is n u mericall y s mall a n d 
si g nifica ntly ne gati ve. I n fact, t he fi n di n gs c orres p o n d well wit h t h ose base d o n Part A. 
C 5 2 4 1 0 0 4: T his st u d y  was desi g ne d as a dr u g-dr u g i nteracti o n st u d y  wit h p har mac o ki netic 
pri mar y  e n d p oi nts a n d a sec o n dar y e n d p oi nt t o c o m pare paire d P K a n d Q Tc i nterval 
para meters pre -d ose t o p ost -d ose of sis u nat o vir. T here were n o cli nicall y si g nifica nt c ha n ges 
i n E C G mea n heart rate, Q R S d urati o n, Q R S a xis, Q T i nter val, Q Tc F i nter val, Q Tc B 
i nter val, or R R i nter val. C o nce ntrati o n-effect m o delli n g was perf or me d t o ass ess 
sis u nat o vir’s effect o n Q Tc F a n d t he P R i nter val; t his re veale d n o c o ncer n of cli nical or 
re g ulat or y rele va nce re gar di n g a Q T- or P R -pr ol o n gi n g effect of sis u nat o vir , neit her as 
m o n ot hera pies n or i n c o m bi nati o n. T his res ult gets f urt her wei g ht b y t he u nif or mit y  acr oss 
t he m o dels a n d a nalys es sets i n vesti gate d a n d b y t he prese nce of a str o n g effect of brea kfast 
w hic h was use d t o s h o w assa y  se nsiti vit y.
M ore detaile d i nf or mati o n a b o ut res ults of cli nical st u dies f or sis u nat o vir ma y  be f o u n d i n 
t he I B, whic h is t he S R S D f or t his st u d y .
2. 3. Be nefit/ Ris k Assess me nt
T here is n o k n o w n be nefit f or healt h y partici pa nt s partici pati n g i n t his trial. T his st u d y is 
desi g ne d pri maril y t o i n vesti gate t he effects of sis u nat o vir o n Q Tc I nter val. 
F or healt h y  partici pa nts partici pati n g i n t his st u d y, n o cli nical be nefit is e x pecte d. T he 
p ur p ose of t he st u d y is t o pr o vi de t he basis f or f urt her cli nical de vel o p me nt of sis u nat o vir as 
a p ote ntial ne w, p har mac ol o gical a ge nt f or t he treat me nt of R S V. As of 1 4 Se pte m ber 2 0 2 2, 
n o s pecific h u ma n ris ks ha ve bee n i de ntifie d; p ost ulate d ris ks base d o n n o ncli nical st u dies 
are s u m marize d i n Secti o n 2. 2. 1 . T he cli nical i m pact of t hese p ote ntial ris ks will be 
mi ni mize d t hr o u g h sta n dar d, i nte nsi ve, i n patie nt m o nit ori n g of t he partici pa nts f oll o wi n g 
a d mi nistrati o n of m ulti ple oral d oses of t he st u d y i nter ve nti o n. Base d o n t he data fr o m P hase 
1 a n d 2 st u dies, t he cli nical safet y pr ofile of sis u nat o vir a p pears t o be acce pta ble at mea n 
( % C V) 
u p t o 
 (
%) n g/ m L a n d mea n ( % C V) 
u p t o 
 (
%). I n t he 
2 8- d a y  rat re peat d ose t oxicit y  st u d y, t he N O A E L was 6 0 m g/ k g/ da y  c orres p o n di n g t o Cma x
of 3 2 2 n g/ m L a n d A U C ta u of 4 7 2 5 n g. h/ m L .
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d reas o na bl y 
e x pecte d A Es of sis u nat o vir ma y  be f o u n d i n t he I B, w hic h is t he S R S D f or t his st u d y. Refer 
t o t he St u d y Inter ve nti o n(s) ta ble i n Secti o n 6. 1 f or a c o m plete descri pti o n of S R S Ds, 
i ncl u di n g S R S Ds f or re q uire d A x M Ps, f or t his st u d y .
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 1
2. 3. 1. Ris k Assess me nt
P ote nti al Ris k of Cli nic al 
Si g nific a nce
S u m m ar y of D at a/ R ati o n ale f or 
Ris k
Miti g ati o n Str ate g y
St u d y I nter ve nti o n(s) sis u n at o vir
He pat o biliar y s yste m effects
De ge nerati ve a n d i nfla m mat or y 
c ha n ges i n t he bile d uct of b ot h rats 
( ≥6 0 m g/ k g/ da y) a n d d o gs ( ≥4 5 
m g/ k g/ da y) i n st u dies of u p t o 2 8 
da ys, wit h ele vate d plas ma le vels of 
A L P, A L T a n d G G T i n d o gs o nl y. 
E vi de nce of rec o ver y f or all fi n di n gs 
f oll o wi n g a 1 4-d a y  treat me nt-free 
peri o d
Sta n da r d mo nit ori n g i ncl u di n g 
la b orat or y (i.e., tra nsa mi nases, 
A L P, G G T) a n d A E 
m o nit ori n g. 
Gastr oi ntesti nal effects
Tra nsie nt d ose -relate d i nci de nce of 
e mesis a n d li q ui d faeces i n d o gs at 
d oses ≥1 5 m g/ k g/ da y i n st u dies u p t o 
2 8 da ys. A d diti o nall y, i nfla m mati o n 
i n d u o de n u m, gall bla d der, a n d li ver 
at 4 5 m g/ k g/ da y n ote d i n 2 8 -d a y  d o g 
st u d y.
I n pre vi o us cli nical st u dies 
sis u nat o vir has bee n ass ociate d w it h 
mil d GI A Es.
As t his is a n i n vesti gati o nal 
a ge nt, t here is s o me ris k t hat is 
miti gate d b y cl ose o bser vati o n 
of A Es, etc. Partici pa nts will be 
cl osel y e val uate d i n a n i n -
patie nt setti n g t o m o nit or f or GI 
A E s. If nee de d, palliati ve 
alle viati n g meas ures s uc h as 
a ntie metics ma y be pr o vi de d.
Re nal effects
De ge nerati o n/re ge nerati o n of 
me d ullar y t u b ules wa s n ote d i n rats 
at ≥1 2 0 m g/ k g/ da y i n st u dies of u p t o 
2 8 da ys; c o nsi dere d n o n -a d verse 
base d o n lac k of cli nical pat h ol o g y 
c ha n ges.
Sta n dar d m o nit ori n g i ncl u di n g 
la b orat or y a n d A E m o nit ori n g.
Car di o vasc ular effects
M y ocar dial de ge nerati o n a n d 
necr osis was n ote d at 2 4 0 m g/ k g/ da y 
( n o n-t olerate d d ose) i n a 1 4-da y rat 
st u d y. 
N o si milar effect i n rats at 1 2 0 
m g/ k g/ da y i n t he 2 8 -d a y  st u d y, or i n 
d o gs at a n y d ose, f or 1 4 or 2 8 da ys.
M o nit ori n g will i ncl u de vital 
si g ns, i ncl u di n g heart rate, a n d 
E C G assess me nts.
P ul m o nar y effects
Vasc ular de ge nerati o n/ necr osis i n 
l u n g at 2 4 0 m g/ k g/ da y a n d e pit helial 
de ge nerati o n/ necr osis i n trac hea at 
1 2 0 m g/ k g/ da y i n 1 4 -d a y  rat st u d y.
T here w ill be sta n dar d safet y 
m o nit ori n g i ncl u di n g vital si g ns 
a n d a d verse e ve nts.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 2
P ote nti al Ris k of Cli nic al 
Si g nific a nce
S u m m ar y of D at a/ R ati o n ale f or 
Ris k
Miti g ati o n Str ate g y
N o si milar effect i n rats at 1 2 0 
m g/ k g/ da y i n t he 2 8 -d a y  st u d y, or i n 
d o gs at a n y d ose, f or 1 4 or 2 8 da ys.
P hase 1 FI H st u d y ( C 5 2 4 1 0 0 1) 
s h o we d n o a d verse cli nicall y 
si g nifica nt c ha n ges i n safet y 
la b orat or y para meters (i ncl u di n g 
tr o p o ni n), E C Gs a n d vital si g ns.
T h y m us effects
L y m p h oi d atr o p h y a n d decrease d 
t h y m us wei g ht a n d re d uce d size of 
t h y m us i n b ot h rats ( ≥ 1 2 0 
m g/ k g/ da y) a n d d o gs ≥1 5 m g/ k g/ da y) 
i n st u dies of u p t o 2 8 da ys. 
E vi de nce of rec o ver y f oll o wi n g a 1 4 -
da y treat me nt -free peri o d.
T hese fi n di n gs are sec o n dar y t o 
stress a n d n ot directl y sis u nat o vir
relate d
Sta n dar d m o nit ori n g i ncl u di n g 
la b orat or y (i.e., c o m plete bl o o d 
c o u nt wit h differe ntial) a n d A E 
m o nit ori n g.  Brief 3- da y c o urse 
re gi me n s h o ul d f urt her li mit 
t his p ote ntial ris k.
St u d y I nter ve nti o n(s) m o xifl o x aci n
Gastr oi ntesti nal dist ur ba nces 
(e g, na usea, diarr h oea, v o miti n g)
A d verse reacti o ns re p orte d f oll o w i n g 
m o xifl o xaci n a d mi nistrati o n
A si n gle d ose of 4 0 0 m g will be 
a d mi nistere d i n t he st u d y. 
Partici pa nts will be m o nit ore d 
f or A E s i n a n i n patie nt cli nical 
researc h u nit.
H y perse nsiti vit y reacti o ns, 
i ncl u di n g a na p h ylactic reacti o ns
A d verse reacti o ns re p orte d f oll o w i n g 
m o xifl o xaci n a d mi nistrati o n
A si n gle d ose of 4 0 0 m g will be 
a d mi nistere d i n t he st u d y. 
Partici pa nts will be m o nit ore d 
b y vitals a n d f or A Es i n a n 
i n patie nt cli nical researc h u nit. 
Partici pa nts wit h hist or y of 
h y perse nsiti vit y or i nt olera nce 
t o q ui n ol o ne a nti bi otics, 
i ncl u di n g m o xifl o xaci n, will be 
e xcl u de d.
Peri p heral ne ur o pat h y, 
e xacer bati o n of m yast he nia 
gra v is, a n d ce ntral ner v o us 
s yste m effects i ncl u di n g 
a gitati o n, i ns o m nia, dizzi ness 
a n d a n xiet y.
A d verse reacti o ns re p orte d f oll o w i n g 
m o xifl o xaci n a d mi nistrati o n
A si n gle d ose of 4 0 0 m g will be 
a d mi nistere d i n t he st u d y. 
Partici pa nts will be m o nit ore d 
f or A Es i n a n i n patie nt cli nical 
researc h u nit. Partici pa nts wit h 
hist or y of m yast he nia gra vis 
are e xcl u de d.
Te n di nitis a n d te n d o n r u pt ure
A d verse reacti o n re p orte d f oll o w i n g 
m o xifl o xaci n a d mi nistrati o n
A si n gle d ose of 4 0 0 m g will be 
a d mi nistere d i n t he st u d y. 
Partici pa nts will be m o nit ore d 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 3
P ote nti al Ris k of Cli nic al 
Si g nific a nce
S u m m ar y of D at a/ R ati o n ale f or 
Ris k
Miti g ati o n Str ate g y
f or A Es i n a n i n patie nt cli nical 
researc h u nit.
Pr ol o n gati o n of t he Q T i nter val 
a n d is olate d cases of t orsa de de 
p oi nte
A d verse reacti o n re p orte d f oll o w i n g 
m o xifl o xa ci n a d mi nistrati o n
A si n gle d ose of 4 0 0 m g will be 
a d mi nistere d i n t he st u d y. 
Partici pa nts will be m o nit ore d 
f or car diac c ha n ges (tele metr y 
a n d E C G) a n d A Es i n a n 
i n patie nt cli nical researc h u nit. 
Partici pa nts wit h k n o w n hist or y 
or ris k fact ors f or pr ol o n g e d 
Q T w ill be e xcl u de d.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 4
2. 3. 2. Be nefit Assess me nt
F or healt h y  partici pa nts partici pati n g i n t his st u d y, n o cli nical be nefit is e x pecte d.
2. 3. 3. O ver all Be nefit /Ris k C o ncl usi o n
S is u nat o vir is n ot e x pecte d t o pr o vi de a ny cli nical be nefit t o healt h y partici pa nts i n t his 
st u d y.
Ta ki n g i nt o acc o u nt t he meas ures t o mi ni mize ris k t o st u d y  partici pa nts, t he p ote ntial ris ks 
i de ntifie d i n ass ociati o n wit h sis u nat o vir are j ustifie d b y t he a ntici pate d be nefits t hat ma y  be 
aff or de d t o partici pa nts wit h R S V.
3. O B J E C TI V E S A N D E N D P O I N T S
O bjecti ves
E n d p oi nts
Pri m ar y: 
Pri m ar y:

T o e val uate t he effect o n Q T i nter val c orrecte d f or 
heart rate ( Q Tc) i nter val i n healt h y partici pa nts , of 
p ossi ble cli nical t hera pe utic c o nce ntrati o ns of 
sis u nat o vir c o m pare d wit h place b o.

Place b o -c orrecte d, baseli ne a dj uste d Q Tc i nter val usi n g 
Fri dericia’s c orrecti o n met h o d ( Q Tc F) of sis u nat o vir at 
e x pecte d ma xi m u m c o nce ntrati o ns ( C ma x) at t he 
.
Sec o n d ar y: 
Sec o n d ar y:

T o e val uate t he safet y a n d t olera bilit y at p ossi ble 
cli nical t hera pe utic c o nce ntrati o ns of sis u nat o vir , 
i ncl u di n g b ut n ot li mite d t o car di o vasc ular safet y. 
A d verse e ve nt ( A E) , E C G assess me nts, vital si g n 
meas ure me nts, a n d cli nical safet y la b orat or y 
meas ure me nts.

T o deter mi ne st u d y se nsiti vit y b y c o m pari n g t he effect 
of m o xifl o xaci n 4 0 0 m g o n Q Tc i nter val wit h place b o 
at hist orical m o xifl o xaci n ti me f or ma xi m u m o bser ve d 
c o nce ntrati o n ( T ma x) of 3- 5 h o urs.

Baseli ne a dj uste d Q Tc F of m o xifl o xaci n a n d place b o at 
T ma x of 3 , 4, a n d 5 h o urs o n Da y 3 .
E x pl or at or y: 
E x pl or at or y:

T o e val uate t he effect of sis u nat o vir o n t he 
electr ocar di o gra m ( E C G) para meters of, heart rate, P R 
i nter val a n d Q R S i nter val.

Baseli ne a dj uste d heart rate, P R i nter val,  a n d Q R S 
i nter vals of sis u nat o vir a n d place b o at eac h p ost d ose 
ti me p oi nt.

T o e val uate t he plas ma p har mac o ki netics ( P K) of 
sis u nat o vir f oll o wi n g m ulti ple oral d ose s.

Plas ma sis u nat o vir para meters, i ncl u di n g C ma x, Tma x a n d 
area u n der t he plas ma c o nce ntrati o n -ti me pr ofile fr o m 
ti me 0 t o 2 4 h o urs ( A U C 2 4) p ost -d ose o n Da y 3 .

T o e x pl ore P K of sis u nat o vir b y micr osa m pli n g 
tec h ni q ue.

C o nce ntrati o n of sis u nat o vir fr o m paire d sa m ples 
o btai ne d via micr osa m pli n g c o m pare d t o ve n o us 
sa m pli n g.
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a P hase 1, m ulti ple -d ose, ra n d o mize d, 3 -treat me nt, 3- peri o d cr oss-o ver, 6 -se q ue nce, 
s p o ns or-o pe n, place b o -a n d p ositi ve-c o ntr olle d st u d y t o be c o n d ucte d i n a p pr o xi matel y 4 2
a d ult healt h y partici pa nts u n der fe d c o n diti o ns . A p pr o xi matel y 4 2   partici pa nts will be 
ra n d o mize d i nt o 6 se q ue nces wit h 7 partici pa nts i n eac h se q ue nce. Partici pa nts assi g ne d t o 
treat me nt A will recei ve  oral d oses of sis u nat o vir a d mi nistere d  
 o ver  da ys i n a 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 5
fe d state. Partici pa nts assi g ne d t o treat me nt B will recei ve  oral d oses of matc hi n g place b o 
a d mi nistere d  
 o ver  da ys i n a fe d state. Partici pa nts assi g ne d t o treat me nt C will 
recei ve  oral d oses of place b o a d mi nistere d  
 f or  da ys f oll o we d b y a si n gle d ose 
of 4 0 0 m g m o xifl o xaci n o n t he m or ni n g of Da y  . Treat me nt assi g n me nts t o sis u nat o vir a n d 
place b o will be bli n de d t o t he partici pa nts , i n vesti gat or a n d C R U staff (e xce pt p har mac y 
staff) b ut o pe n t o t he s p o ns or. M o xifl o xaci n a d mi nistrati o n o n Da y   will be u n bli n de d.
F or i n di vi d ual partici pa nts, t he t otal d urati o n of partici pati o n fr o m t he scree ni n g visit t o t he 
f oll o w-u p visit will be a p pr o xi matel y  1 4 wee ks.  Scree ni n g e val uati o n will occ ur wit hi n t he 
2 8 da y s pri or t o d osi n g i n t he first treat me nt peri o d. D uri n g eac h treat me nt peri o d, eli gi ble 
partici pa nts w h o meet t he e ntr y  criteria will be a d mitte d o n Da y -1, pri or t o treat me nt 
a d mi nistrati o n o n Da y 1, a n d will resi de i n t he P C R U u ntil c o m pleti o n of pr ot oc ol 
assess me nts o n Da y 4. Partici pa nts m a y  be disc har ge d bet wee n st u d y peri o ds at t he 
discreti o n of t he i n vesti gat or. T here will be a was h o ut of at least 7 d a y s bet wee n d ose 
a d mi nistrati o ns i n c o nsec uti ve cr oss o ver treat me nt peri o ds. F oll o w -u p c o ntact will be ma de 
at least 2 8 cale n dar da ys a n d u p t o 3 5 cale n dar da ys after t he last a d mi nistrati o n of t he 
i n vesti gati o nal pro d uct t o ca pt ure a n y  p ote ntial A Es a n d c o nc o mita nt treat me nts, a n d t o 
c o nfir m a p pr o priate c o ntrace pti o n usa ge . Co ntact wit h t he partici pa nt m a y  be d o ne via 
p h o ne. F or eac h partici pa nt, t he d urati o n of partici pati o n fr o m Peri o d 1 a d missi o n t o 
dis hc h ar ge will be a p pr o xi matel y  4 wee ks. T he f oll o w -u p call will occ ur u p t o 5 wee ks after 
last d ose of st u d y dr u g.
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
T his p ur p ose of t his st u d y is t o assess t he effect of sis u nat o vir o n Q T i nter val as 
rec o m me n de d by t he I C H E 1 4 g ui deli ne a n d i n I C H E 1 4 Q & As ( R 3). 7 T he c o nce ntrati o n -Q T 
a nal ys is is defi ne d as t he pri mar y a nalys is i n t his st u d y a n d ser ves as t he pri mar y basis f or 
t he decisio n t o classif y  t he Q T pr ol o n gati o n ris k f or sis u nat o vir.
Preli mi nar y  
 a nal ysis of S A D a n d M A D data ( C 5 2 4 1 0 0 1) f or sis u nat o vir s u g geste d 
t hat o verall, t he m o del pre dicts  
 d oses of u p t o  
 m g a n d  
 d oses of u p t o  
 
m g of R V 5 2 1 wit h  
 o n E C G para meters. T he effects of sis u nat o vir o n Q T i nter val 
was e val uate d i n Part A (si n gle d ose a d mi nistrati o n) of t he st u d y. T his part of t he st u d y di d 
n ot i ncl u de a place b o gr o u p, b ut si nce t he l o west d ose ( 1 0 m g) res ulte d i n e x p os ure bel o w 
t he li mit of detecti o n, t he data fr o m t his gr o u p was used as a s urr o gate f or place b o. A m o del 
was b uilt t o i n vesti gate t he effect of R V 5 2 1 o n Q Tc F at c o nce ntrati o ns see n i n Part A of t he 
st u d y. I n partic ular, pre dicti o ns of t he effect at t he ge o metric mea n of t he i n di vi d ual Cma x
val ues u n der eac h d ose wit h q ua ntifia ble c o nce ntrati o n a n d at least 6 partici pa nts were gi ve n 
t o get her wit h t w o-si de d 9 0 % c o nfi de nce i nter vals. As t he res ults 
 a ny effect of 
R V 5 2 1 o n 
, a n d, i n dee d i n dicate n o effect at all, a m ore i n-de pt h 
i n vesti gati o n i nt o t he a p pr o priate ness of t he ass u m pti o n of li nearit y or a bse nce of P K-P D -
h y steresis was n ot c o nsi dere d necessar y. A si milar e val uati o n was perf or me d f or data 
o btai ne d fr o m Part B ( place b o c o ntr olle d, m ulti ple d ose a d mi nistrati o n) a n d a si milar 
c o ncl usi o n was reac he d w here n o effect of treat me nt o n Q Tc F was o bser ve d.
I n or der t o ac hie ve t hera pe utic c o nce ntrati o ns t he c urre nt st u dy will d ose t o stea d y state , 
w hic h is ac hie ve d after a p pr o xi matel y 
 s o t he c urre nt st u d y will e val uate 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 6
Q Tc i n ter val at stea dy state o n Da y  3. As t he e x p os ure of sis u nat o vir i ncreases i n a greater 
t ha n d ose pr o p orti o nal ma n ner, t he c urre nt st u d y will e val uate t he hi g hest feasi ble d ose t hat 
is pr ojecte d t o be well t olerate d. I n t his st u d y, a n i nitial d ose of 
 has bee n 
selecte d t o ac hie ve hi g h cli nical e x p os ure base d o n i nter p olati o n bet wee n t he 
 m g a n d 
 m g e x p os ures o bser ve d i n  
. T he safet y a n d P K data fr o m a p pr o xi matel y  t he 
first 7 partici pa nts ma y  be assesse d a n d if o bser ve d e x p os ure of 
 is l o wer t ha n 
pre dicte d (see Ta ble 3 ) a n d d oes n ot c o ver t he hi g h cli nical e x p os ure, t he n t he d ose will be 
i ncrease d t o 
.
T he effect of f o o d o n t he p har mac o ki netics of sis u nat o vir has bee n varia ble i n P hase 1 
st u dies. H o we ver, t he effect of f o o d o n t he p har mac o ki netics of sis u nat o vir usi n g t he 
f or m ulati o n t o be use d i n t his st u d y ( dr y p o w der ble n d i n ca ps ules) s h o we d mi ni mal f o o d 
effect. T he c urre nt st u d y will a d mi nister st u d y  i nter ve nti o n u n der fe d c o n diti o ns.  T he im pact 
of f o o d o n E C G meas ure me nts will be c o ntr olle d b y  c o nsiste nt ti mi n g a n d c o nte nt of meals 
acr oss sis u nat o vir, place b o, a n d m o xifl o xaci n treat me nts. 
A c o nc urre nt place b o c o ntr ol will be i ncl u de d i n acc or da nce wit h I C H E 1 4 rec o m me n dati o ns 
t o e n ha nce t he vali dit y of t his st u d y a n d t o a v oi d p ote ntial biases ass ociate d wit h st u d y 
pr oce d ures. 
T o i ncrease t he c o nfi de nce t hat t his st u d y  has t he a bilit y t o detect a Q Tc pr ol o n gati o n i n t he 
ra n ge of a p pr o xi matel y 5 ms, a c o nc urre nt p ositi ve c o ntr ol will be i nclu de d t o esta blis h assa y  
se nsiti vit y. I n t his st u d y, m o xifl o xaci n will be use d as t he acti ve c o ntr ol. M o xifl o xaci n is a 
fl u or o q ui n ol o ne a nti bi otic t hat pr o d uces c o nsiste nt a n d pre dicta ble Q T pr ol o n gati o n a n d is 
r o uti nel y use d as a p ositi ve c o ntr ol i n T Q T stu dies. Base d o n rece nt Pfizer e x perie nce fr o m 
T Q T trials c o n d ucte d at i nter nal C R Us usi n g a ut o mate d rea di n gs, a si n gle 4 0 0 m g d ose of 
m o xifl o xaci n pr o d uces a ma xi m u m mea n heart rate-c orrecte d Q T i nter val usi n g Fri dericia’s 
c orrecti o n ( Q Tc F) c ha n ge fr o m bas eli ne bet wee n 7. 9 msec a n d 1 1. 0 msec 2 t o 5 h o urs 
p ost d ose ti me p oi nts wit h mac hi ne rea di n gs. T he tma x of m o xifl o xaci n is dela y e d b y  ≥1 h o ur 
w he n a d mi nistere d u n der fe d c o n diti o ns 8 ,9, wit h dela ys i n t he pea k effects o n Q Tc t o 4 h o urs 
p ost -d ose 9. E nca ps ulati o n of c o m merciall y  a vaila ble m o xifl o xaci n ta blets t o ac hie ve 
bli n di n g has t he p ote ntial t o ha ve a n i m pact o n a bs or pti o n, t heref ore e nca ps ulati o n will n ot 
be e m pl o y e d a n d m o xifl o xaci n will be a d mi nistere d o n Da y  3 i n a n o pe n ma n ner. Bl o o d 
sa m ples fr o m partici pa nt s ra n d o mize d t o place b o or m o xifl o xaci n will be c ollecte d a n d 
retai ne d, b ut will n ot be r o uti nel y a nal yze d.
All E C G meas ure me nts will be perf or me d i n tri plicate at eac h n o mi nal sa m pli n g ti me (see
Sc he d ule of Acti vities a n d Electr ocar di o gra m Secti o n 8. 3. 3 ). Tri plicate meas ure me nts are 
i nte n de d t o re d uce t he i ntri nsic varia bilit y a n d meas ure me nt err or ass ociate d wit h E C G 
meas ure me nt of t he Q T/ Q Tc i nter val. T he c ollecti o n of E C Gs at m ulti ple ti me p oi nts is 
perf or me d t o ta ke i nt o c o nsi derati o n t he di ur nal patter n a n d varia bilit y  of Q T i nter vals, 
de pe n de nt u p o n m ulti ple fact ors i ncl u di n g acti vit y le vel, p ost ural c ha n ges, circa dia n patter ns 
a n d f o o d i n gesti o n. T he sa m pli n g ti me p oi nts ha ve bee n c h ose n base d o n t he e x pecte d P K 
pr ofiles of sis u nat o vir a n d m o xifl o xaci n. T he ti me t o reac h ma xi m u m c o nce ntrati o n ( Tma x ) 
f or sis u nat o vir is a p pr o xi matel y 4 t o 6 h o ur p ost d ose base d o n pre vi o us P hase 1 a n d 2 st u dies 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 7
( S u m mar y of sis u nat o vir P har mac o ki netics S ecti o n 8. 5 ). T his sc he d ule will als o all o w pea k 
Q T effects wit h m o xifl o xaci n,  t o be ca pt ure d. 7
T o mi ni mize t he ris ks of C O VI D-1 9 relate d c o m plicati o ns t o partici pa nts a n d t he st u d y  site 
pers o n nel, assess me nt of ris k f or, s y m pt o ms of or testi n g f or C O VI D- 1 9 ma y  be perf or me d 
at scree ni n g, a d missi o n t o t he C R U, a n d/ or at ot her ti mes d uri n g t he st u d y  at i n vesti gat or 
discreti o n a n d acc or di n g t o l ocal site p olicies.
As t his is healt h y  partici pa nt st u d y, t he use of c o nc o mita nt me dicati o ns i n t his st u d y is 
e x pecte d t o be mi ni mal. Ne vert heless, acc or di n g t o t he D DI ris k assess me nt f or sis u nat o vir
as descri be d i n Secti o n 2. 2. 2 , sis u nat o vir is a m o derate i n hi bit or of C Y P 3 A 4 a n d is pr ojecte d 
t o be a wea k i n hi bit or of 
. F or t his reas o n se nsiti ve a n d narr o w TI C Y P 3 A 4 
s u bstrates a n d se nsiti ve a n d narr o w T I  
 s u bstrates are pr o hi bite d i n t his st u d y. Si nce 
sis u nat o vir is a P-g p a n d C Y P 3 A 4 s u bstrate, str o n g a n d m o derate C Y P 3 A 4 a n d P-g p 
i n hi bit ors or i n d ucers are pr o hi bite d. Lastl y, d ue t o ris k of  
 a n d  
 i n hibiti o n, 
se nsiti ve s u bstrates of t hese tra ns p orters are pr o hi bite d. Use of s pecific pr o hi bite d 
pri or/c o nc o mita nt t hera pies are o utli ne d i n A p pe n di x 9 .
4. 2. 1. C h oice of C o ntr ace pti o n/ B arrier Re q uire me nts
T here is n o s us pici o n of h u ma n terat o ge nicit y base d o n t he i nte n de d p har mac ol o g y of t he 
c o m p o u n d. H u ma n re pr o d ucti ve safet y data are li mite d f or sis u nat o vir, t heref ore t he use of a 
hi g hl y effecti ve met h o d of c o ntrace pti o n is re q uire d f or all fertile partici pa nts (see 
A p pe n di x 4 ).
4. 3. J ustific ati o n f or D ose
C o nsi deri n g t he e x p os ure of sis u nat o vir i ncreases i n a greater t ha n d ose pr o p orti o nal ma n ner , 
t he c urre nt st u d y will e val uate t he hi g hest feasi ble d ose t hat is well t olerated. T he
p har mac o ki netics of
 m g a n d 
 m g Q 1 2 h o ur d ose s ha ve bee n e val uate d i n st u d y 
wit h t he sa me f or m ulati o n t hat is t o be use d i n t his st u d y ( draft P K data a vaila ble, 
fi nal re p orti n g pe n di n g). Draft res ults fr o m  
 i n dicate t hat t he 
 m g Q 1 2 hr
sis u nat o vir d ose u n der fe d c o n diti o ns res ulte d i n mea n e x p os ure a b o ve rat N O A E L 
ass ociate d wit h t he 2 8-d a y  G L P st u d y, w hereas e x p os ures ass ociate d wit h 2 0 0 m g Q 1 2 hr 
were c o nsiste nt wit h t h ose o bser ve d i n pre vi o us P hase 1 st u dies wit h sis u nat o vir, i ncl u di n g 
t he h u ma n c halle n ge st u d y ( C 5 2 4 1 0 0 2). As of 4 A pril 2 0 2 3, i n st u d y  
 t here ha ve 
bee n n o S A Es attri b uta ble t o sis u nat o vir a n d n o st u d y  dr u g disc o nti n uati o n d ue t o a n A E . 
T he m ost c o m m o n A Es a re GI relate d ( na usea, diarr hea, a b d o mi nal pai n/ diste nti o n) , 
c o nsiste nt wit h p re vi o us st u dies. N o cli nicall y mea ni n gf ul tre n ds were see n wit h E C G 
para meters, vital si g ns or la b orat or y  val ues.
I n t his st u dy, a n i nitial d ose of 
 has bee n selecte d. Ta ble 3 s h o ws t he 
a ntici pate d mea n stea d y-state e x p os ure at t he P hase 2/ 3 cli nical d ose ( 2 0 0 m g Q 1 2 hr) as well 
as t he pre dicte d mea n e x p os ure at 
 i n t his st u d y base d o n i nter p olati o n 
bet wee n t he
m g  a n d 
m g e x p os ures o bser ve d i n 
. Ta ble 3 als o c o m par es 
pr ojecte d e x p os ure at t he 
m g d ose le vel t o t hat o bser ve d at t he N O A E L i n t he 2 8- d a y  rat 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 8
G L P t o xic ol o g y  st u d y.  T hese data i n dicate t hat t he e x pecte d e x p os ure at t he 
-m g d ose 
le vel is c o m para ble t o t he rat N O A E L.
T a ble 3.
S u m m ar y of Preli mi n ar y ( U n a u dite d) Pl as m a P K P ar a meters of 
Sis u n at o vir F oll o wi n g M ulti ple Or al D ose A d mi nistr ati o n f or 5 D a ys i n 
He alt h y P artici p a nts i n 
, C o m p are d t o Pre dicte d E x p os ures 
rel ati ve t o R at N O A E L
 
P re dicte d 
D DI 
effect o n  
2 0 0 m g 
Q 1 2 hr 
(fe d)
R at 
N O A E L 6 0 
m g/ k g/ d a y
P a r a m eter a, U nits
m g 
Q 1 2 hr 
(fe d), 
n = 1 2 b
 mg 
Q 1 2 hr 
(fe d), 
n = 5
Pre dicte d 
2 5 0 m g 
Q 1 2 hr 
(fe d)
Pre dicte d 
3 0 0 m g 
Q 1 2 hr 
(fe d)
D a y 5 ( Ste a d y St ate)
C ma x ( n g/ m L)
9 7. 9 ( 6 5)
8 1 1. 0 
( 4 1)
3 2 2
A U C ta u ( n g. hr/ m L)
7 8 7. 3 ( 7 6)
7 2 4 5. 2 
( 4 7)
4 7 2 5 c
a ge o metric mea n ( ge o metric % C V).
b Data c ollecte d fr o m 9 partici pa nts. 3 partici pa nts recei ve d  
 m g (fe d) i n Peri o d 1 a n d re peate d i n 
Peri o d 2 after w as h o ut peri o d.
c A U C o ver 2 4 h o urs.
F oll o wi n g e val uati o n of safet y a n d sis u nat o vir P K data fr o m at least 7 partici pa nts i n t his 
st u d y, at S p o ns or discreti o n t he d ose of sis u nat o vir ma y be i ncrease d t o 
pr o vi de d t hat t he pr ojecte d e x p os ure at t he hi g her d ose is n o m ore t hat 2 0 % a b o ve t he rat 
N O A E L mea n e x p os ures f or t he 2 8 da y G L P t o x st u d y . T hese pre dic te d e x p os ures w o ul d be 
well bel o w t he o bser ve d e x p os ure wit h a n acce pta ble safet y pr ofile fr o m t he o n g oi n g st u d y 
. T his will all o w c haracterizati o n of c o nce ntrati o n -Q Tc a nal ysis at hi g her 
e x p os ures t o m ore f ull y u n dersta n d t he p ote ntial effects at hi g h cli nical e x p os ures.
Gi ve n t he e x p os ures of  
 m g Q 1 2 hr e xcee de d N O A E L e x p os ures wit h a n acce pta ble 
safety pr ofile ( St u d y  
), r o b ust m o nit ori n g of partici pa nts i n t he P C R U, li mite d 
d urati o n of d osi n g , a n d varia bilit y i n e x p os ure at N O A E L of 6 0 m g/ k g/ da y , cr ossi n g t he 
mea n N O A E L li mits w o u l d n ot p ose a safety c o ncer n f or partici pa nts . A d diti o nall y , t he 
t o xicit y fi n di n gs a b o ve t he N O A E L ( 1 2 0 m g/ k g/ da y) were pre d o mi na ntl y tra nsie nt i n nat ure 
a n d re verse d after 1 4 da ys off treat me nt.
I n st u dy C 5 2 4 1 0 0 4 , c oa d mi nistrati o n wit h itrac o naz ole, a str o n g C Y P 3 A i n hi bit or, i ncrease d 
e x p os ure of sis u nat o vir b y a p pr o xi matel y 3 t o 3. 5 -f ol d. T h us, t he pre dicte d hi g h cli nical 
e x p os ure f or 2 0 0 m g Q 1 2 h o urs u n der fe d c o n diti o ns is a Cma x of  
 n g/ m L  a n d A U Cta u of 
 n g. hr/ m L. T he safet y a n d P K data fr o m a p pr o xi matel y  t he first 7 partici pa nts ma y  be 
assesse d a n d i f o bser ve d e x p os ure of 
u n der fe d c o n diti o ns is l o wer t ha n 
pre dicte d (see Ta ble 3 ) a n d d o n ot c o ver t he hi g h cli nical e x p os ure, t he n t he d ose will be 
i ncrease d t o 
, as descri be d a b o ve. A si n gle 4 0 0 m g d ose of m o xifl o xaci n has 
bee n use d as sta n dar d p ositi ve c o ntr ol i n Q T st u dies a n d will be i ncl u de d as a n o pe n -la bel 
treat me nt.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C C
I
C CI
C CI
C CI
C CI
C C
I
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 3 9
I n or der t o ac hie ve t hera pe utic c o nce ntrati o ns t he c urre nt st u dy will d ose t o stea d y state. 
P hase 1 st u dies i n dicate t hat stea d y state is ac hie ve d after a p pr o xi matel y 
 
 s o t he c urre nt st u d y will e val uate Q Tc i nter val at stea d y state o n Da y . Treat me nt A 
a n d B will recei ve sis u nat o vir a n d place b o  
 f or  d oses, res pecti vel y. T o mai ntai n 
c o nsiste nc y bet wee n treat me nt gr o u ps, Treat me nt C will c o nsist of place b o  
 f or  
da y s (  d oses) a n d m o xifl o xaci n a d mi nistere d o n Day . 
4. 4. E n d of St u d y Defi niti o n
T he e n d of t he st u d y is defi ne d as t he date of t he last visit of t he last partici pa nt i n t he st u d y. 
A partici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y  if t he y ha ve c o m plete d all peri o ds of 
t he st u d y, i ncl u di n g t he last visit.
5. S T U D Y P O P U L A TI O N
T his st u d y  ca n f ulfill its o bjecti ves o nl y if a p pr o priate partici pa nt s are e nr olle d, i ncl u di n g 
partici pa nts acr oss di verse a n d re prese ntati ve racial a n d et h nic bac k gr o u n ds. Use of a 
prescree n i n g t o ol is utilize d f or st u dy recr uit me nt p ur p oses , it will i ncl u de c ollecti o n of 
i nf or mati o n t hat reflects t he e nr oll me nt of a di verse partici pa nt p o p ulati o n i ncl u di n g, w here 
per mitte d u n der l ocal re g ulati o ns, a ge, se x, a n d race, a n d et h nicit y . T he f oll o wi n g eli gi bilit y 
criteria are desi g ne d t o select partici pa nt s f or w h o m partici pati o n i n t he st u d y  is c o nsi dere d 
a p pr o priate. All rele va nt me dical a n d n o n me dical c o n diti o ns s h o ul d be ta ke n i nt o 
c o nsi derati o n w he n deci di n g w het her a partic ular partici pa nt is s uita ble f or t his pr ot oc ol.
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria , als o 
k n o w n as pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d.
5. 1. I ncl usi o n Criteri a
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y:
A ge a n d Se x :
1.
Partici pa nts a ge d 1 8 t o 6 5 ye ars, i ncl usi ve, at t he ti me of si g ni n g of t he I CD.  

All fertile partici pa nts m ust a gree t o use a hi g hl y effecti ve met h o d of 
c o ntrace pti o n ( See A p pe n di x 4 ).

Refer t o A p pe n di x 4 f or re pr o d ucti ve criteria f or male (Secti o n 1 0. 4. 1 ) a n d fe male 
(Secti o n 1 0. 4. 2 ) partici pa nts.
2.
Male a n d fe male partici pa nts w h o are o vertl y healt h y as deter mi ne d b y me dical 
e val uati o n i ncl u di n g me dical hist or y , p h ysical e xa mi nati o n, i ncl u di n g bl o o d press ure, 
p ulse rate, sta n dar d 1 2 -lea d E C G, a n d la b orat or y tests.
Ot her I ncl usi o n Criteri a :
3.
B MI of 1 7. 5 t o 3 2 k g/ m 2; a n d a t otal b o d y  wei g ht > 5 0 k g ( 1 1 0 l b). 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 0
4.
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt as descri be d i n A p pe n di x 1: Re g ulat or y , 
Et hical, a n d St u d y  O versi g ht C o nsi derati o ns w hic h i ncl u des c o m plia nce wit h 
re q uire me nts a n d restricti o ns liste d i n t he IC D a n d i n t his pr ot oc ol.
5. 2. E xcl usi o n Criteri a
Partici pa nts are e xcl u de d fr o m t he st u d y  if a n y of t he f oll o wi n g criteria a p pl y:
Me dic al C o n diti o ns:
1.
E vi de nce or hist or y  of cli nicall y si g nifica nt he mat ol o gical, re nal, e n d ocri ne, 
p ul m o nar y , gastr oi ntesti nal, car di o vasc ular, he patic, ps yc hiatric, ne ur ol o gi cal, or 
aller gic disease (i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, as y m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).

A n y  c o n diti o n p ossi bl y affecti n g dr u g a bs or pti o n (e g, gastrect o m y, 
c h olec ystect o my).

Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve testi n g f or HI V, 
H Bs A g, H Bc A b, or H C V A b. He patitis B vacci nati o n is all o we d.

P ositi ve test res ult f or S A R S -C o V -2 i nfecti o n o n Da y  - 1.
2.
Partici pa nts, w h o acc or di n g t o t he pr o d uct la bel f or m o xifl o xaci n, w o ul d be at 
i ncrease d ris k if d ose d wit h m o xifl o xaci n, i ncl u di n g b ut n ot li mite d t o partici pa nts 
wit h hist or y  of myast he nia gra vis, te n di nitis/te n d o n r u pt ure, hist or y  of 
h y perse nsiti vit y , aller g y, se vere a d verse dr u g reacti o n or i nt olera nce t o q ui n ol o ne 
a nti bi otics, i ncl u di n g m o xifl o xaci n .
3.
Self -re p orte d hist or y or ris k fact ors f or Q T pr ol o n gati o n or t orsa des de p oi ntes (e g, 
or ga nic heart disease, c o n gesti ve heart fail ure, h y p o kale mia, h y p o ma g nesae mia, 
c o n ge nital l o n g Q T s y n dr o me, m y ocar dial isc he mia or i nfarcti o n), c o n ge nital 
deaf ness , fa mil y hist or y of car diac arrest or s u d de n deat h, a n d fa mil y hist or y of l o n g 
Q T s y n dr o me.
4.
Ot her me dical or ps y c hiatric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past year) or 
acti ve s uici dal i deati o n/be ha vi or or la b orat or y  a b n or malit y or ot her c o n diti o ns or
sit uati o ns relate d t o C O VI D-1 9 pa n de mic t hat ma y i ncrease t he ris k of st u d y 
partici pati o n or , i n t he i n vesti gat or’s j u d g me nt, ma ke t he partici pa nt i na p pr o priate f or 
t he st u d y.
Pri or/ C o nc o mit a nt T her a p y:
5.
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d die tar y a n d her bal s u p ple me nts 
wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n wit h t he e xce pti o n of a nti bi otics a n d m o derate/str o n g C Y P 3 A i n d ucers 
or ti me-de pe n de nt i n hi bit ors w hic h are pr o hi bite d wit hi n 1 4 d a ys pl us 5 half-li ves 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 1
pri or t o t he first d ose of st u d y  i nter ve nti o n. ( Refer t o Secti o n 6. 9 Pri or a n d 
C o nc o mita nt T hera p y f or a d diti o nal details).
6.
C urre nt use of a n y pr o hi bite d c o nc o mita nt me dicati o n(s) or partici pa nt 
u n willi n g/ u na ble t o use a per mitte d c o nc o mita nt me dicati o n(s). 
Pr i or/ C o nc urre nt Cli nic al St u d y E x perie nce:
7.
Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal pr o d uct ( dr u g or vacci ne) wit hi n 
3 0 da y s ( or as deter mi ne d b y t he l ocal re q uire me nt) or 5 half -li ves prece di n g t he first 
d ose of st u d y i nter ve nti o n use d i n t his st u d y  ( w hic he ver is l o n ger). 
Di a g n ostic Assess me nts:
8.
A p ositi ve uri ne dr u g test .
9.
F or fe males, pre g na nc y , as i n dicate d b y a p ositi ve ser u m pre g na nc y test at scree ni n g 
a n d/ or p ositi ve uri ne pre g na nc y  test i n W O C B P at Da y - 1.
1 0. Scree ni n g s u pi ne B P ≥1 4 0 m m H g (s ys t olic) or ≥9 0 m m H g ( diast olic), f oll o wi n g at 
least 5 mi n utes of s u pi ne rest. If B P is ≥1 4 0 m m H g (s ys t olic) or ≥9 0 m m H g 
( diast olic), t he B P s h o ul d be re peate d 2 m ore ti mes a n d t he a vera ge of t he 3 B P 
val ues s h o ul d be us e d t o deter mi ne t he partici pa nt’s eli gi bilit y .
1 1. St a n dar d 1 2 -lea d E C G t hat de m o nstrates cli nically rele va nt a b n or malities t hat ma y 
affect partici pa nt safet y or i nter pretati o n of st u d y res ults (e g, Q Tc F  > 4 5 0 ms, 
c o m plete L B B B, si g ns of a n ac ute or i n deter mi n ate- a ge m y o car dial i nfarcti o n, S T -T 
i nter val c ha n ges s u g gesti ve of m yocar dial isc he mia, sec o n d - or t hir d - de gree A V 
bl oc k, or seri o us bra d yarr h yt h mias or tac h ya rr hyt h mias). If t he u nc orrecte d Q T 
i nter val is > 4 5 0 ms, t his i nter val s h o ul d be rate -c orrecte d usi n g t he Fri dericia met h o d 
o nl y  a n d t he res ulti n g Q Tc F s h o ul d be use d f or decisi o n ma ki n g a n d re p orti n g. If 
Q Tc F e xcee ds 4 5 0 ms, or Q R S e xcee ds 1 2 0 ms, t he E C G s h o ul d be re peate d t wice
a n d t he a vera ge of t he 3 Q Tc F or Q R S val ues use d t o deter mi ne t he part ici pa nt’s 
eli gi bilit y. Partici pa nts wit h a n a vera ge Q Tc i nter val > 4 5 0 millisec o n ds ( ms) will n ot 
be all o we d t o partici pate i n t he st u d y. C o m p uter -i nter prete d E C Gs s h o ul d be o verrea d 
b y  a p hys icia n e x perie nce d i n rea di n g E C Gs bef ore e xcl u di n g a partici pa nt .
1 2. Partici pa nts wit h A N Y of t he f oll o wi n g a b n or malities i n cli nical la b orat or y  tests at 
scree ni n g, as assesse d by t he st u d y -s pecific la b orat or y a n d c o nfir me d by a si n gle 
re peat test, if dee me d necessar y:

G F R < 6 0 m L / mi n/ 1. 7 3 m 2 base d o n C K D-E PI e q uati o n;

A S T or A L T le vel ≥1. 5 x U L N;

Ga m ma -G T > 1. 2 x U L N;
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 2

Al kali ne p h os p hatase > 1. 2 x U L N;

T otal bilir u bi n le vel ≥1. 5 × U L N; partici pa nts wit h a hist or y of Gil bert’s 
s yn dr o me ma y  ha ve direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or t his st u d y 
pr o vi de d t he direct bilir u bi n le vel is ≤U L N.
Ot her E xcl usi o n Criteri a :
1 3. Hist or y  of alc o h ol a b use or bi n ge dri n ki n g a n d/ or a n y ot her illicit dr u g use or 
de pe n de nce wit hi n 6 m o nt hs of Scree ni n g. Bi n ge dri n ki n g is defi ne d as a patter n of 
5 ( male) a n d 4 (fe male) or m ore alc o h olic dri n ks i n a b o ut 2 h o urs . As a ge neral r ule, 
alc o h ol i nta ke s h o ul d n ot e xcee d 1 4 u nits per wee k ( 1 u nit = 8 o u nces ( 2 4 0 m L ) beer, 
1 o u nce ( 3 0 m L ) of 4 0 % s pirit, or 3 o u nces ( 9 0 m L ) of wi ne).
1 4. Use of t o bacc o or nic oti ne- c o ntai ni n g pr o d uct s i n e xcess of t he e q ui vale nt of 5 
ci garettes/ da y or 2 c he ws of t o bacc o/ da y.
1 5. Bl o o d d o nati o n (e xcl u di n g plas ma d o nati o ns) of a p pr o xi matel y  1 pi nt ( 5 0 0 m L ) or 
m ore wit hi n 6 0 da y s pri or t o d osi n g.
1 6. U n willi n g or u na ble t o c o m pl y  wit h t he criteria i n t he Li fest yle C o nsi derati o ns
secti o n of t his pr ot oc ol.
1 7. I n vesti gat or site staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d s p o ns or a n d s p o ns or 
dele gate e m pl o y ees directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers.
5. 3. Lifest yle C o nsi der ati o ns
T he f oll o wi n g g ui deli nes are pr o vi de d:
5. 3. 1. C o ntr ace pti o n 
T he i n vesti gat or or t heir desi g nee, i n c o ns ultati o n wit h t he partici pa nt, will c o nfir m t hat t he 
partici pa nt is utilizi n g a n a p pr o priate met h o d of c o ntrace pti o n f or t he i n di vi d ual partici pa nt 
a n d t heir part ner(s) fr o m t he per mitte d list of c o ntrace pti o n met h o ds (see A p pe n di x 4 ,
Secti o n 1 0. 4. 4 ) a n d will c o nfir m t hat t he partici pa nt has bee n i nstr ucte d i n its c o nsiste nt a n d 
c orrect use. At ti me p oi nts i n dicate d i n S o A , t he i n vesti gat or or desi g nee will i nf or m t he 
partici pa nt of t he nee d t o use hi g hl y effecti ve c o ntrace pti o n c o nsiste ntl y a n d c orrectl y a n d 
d oc u me nt t he c o n versati o n a n d t he partici pa nt’s affir mati o n i n t he partici pa nt’s c hart. 
Partici pa nts nee d t o affir m t heir c o nsiste nt a n d c orrect use of at least 1 of t he selecte d 
met h o ds of c o ntrace pti o n, c o nsi deri n g t hat t heir ris k f or pre g na nc y  ma y ha ve c ha n ge d si nce 
t he last visit. 
I n a d diti o n, t he i n vesti gat or or desi g nee will i nstr uct t he partici pa nt t o call i m me diatel y if t he 
selecte d c o ntrace pti o n met h o d is disc o nti n ue d a n d d oc u me nt t he re q uire me nt t o use a n 
alter nate pr ot oc ol-s pecifie d met h o d, i ncl u di n g if t he partici pa nt will n o l o n ger use a bsti ne nce 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 3
as t he selecte d c o ntrace pti o n met h o d, or if pre g na nc y is k n o w n or s us pecte d i n t he partici pa nt 
or part ner.
5. 3. 2.
Me als a n d Diet ar y Restricti o ns

Partici pa nt s m ust a bstai n fr o m all f o o d a n d dri n k (e xce pt water) at least 4 h o urs pri or 
t o a n y safet y la b orat or y e val uati o ns.

T o mi ni mize i m pact o n baseli ne E C G meas ure me nt, w ater is restricte d 1 h o ur pri or t o 
st u d y i nter ve nti o n a d mi nistrati o n o n Da y  1, e xce pt wit h t he m or ni n g meal . O n Da y  3, 
w ater is restricte d 1 h o ur pri or t o st u d y  i nter ve nti o n, e xce pt wit h meals, a n d 2 h o urs 
after d osi n g. Partici pa nt s will be restricte d t o c o ns u mi n g a m bie nt te m perat ure dri n ks 
fr o m Da y 1, ( pri or t o baseli ne E C G meas ure me nts), u ntil fi nal E C G meas ure me nts 
ha ve bee n c ollecte d i n eac h st u d y  peri o d. N o ncaffei nate d dri n ks (e xce pt gra pefr uit or 
gra pefr uit -relate d citr us fr uit j uices— see bel o w) ma y be c o ns u me d wit h meals a n d 
t he e ve ni n g s nac k.  

O n d osi n g d a ys, partici pa nts will c o ns u me a sta n dar d meal a p pr o xi matel y 3 0 mi n utes 
pri or t o m or ni n g d osi n g. T he y  s h o ul d be e nc o ura ge d t o c o m plete t heir meals b y 
a p pr o xi matel y 1 0 mi n utes pri or t o a ntici pate d d osi n g. Lu nc h will be pr o vi de d 
a p pr o xi matel y 4 h o urs after d osi n g (ie, f oll o wi n g t he sc he d ule d 4 h o ur E C G a n d P K 
meas ure me nts) a n d will be at a p pr o xi matel y  t he sa me ti me ( ± 1 5 mi n utes) f or eac h 
st u d y da y acr oss all d osi n g peri o ds. O n Da y  3, sta n dar d meals s h o ul d be as si milar as 
p ossi ble f or all partici pa nts. 

Di n ne r will be pr o vi de d a p pr o xi matel y 1 1 t o 1 3 h o urs after A M d osi n g (ie, 
a p pr o xi matel y 3 0 mi n utes bef ore t he P M d ose ) a n d will be at a p pr o xi matel y t he sa me 
ti me ( ± 1 5 mi n utes) f or eac h st u d y d a y acr oss all d osi n g peri o ds.

A n e ve ni n g s nac k ma y  be per mitte d after c o m pleti o n of t he 1 2 -h o ur E C G a n d P K 
meas ure me nts .

T he ti mi n g of meals m ust be sta n dar dize d ( wit h a n acce pta ble de viati o n of ± 1 5 
mi n utes) bet wee n st u d y da y s a n d st u d y peri o ds. T he ti mi n g of meals a n d s nac ks m ust 
be rec or de d. It s h o ul d be n ote d if a partic i pa nt fails t o c o ns u me t he maj orit y of a 
meal.

Partici pa nts will refrai n fr o m c o ns u mi n g re d wi ne, gra pefr uit , or gra pefr uit -relate d 
citr us fr uits (e g, Se ville ora n ges, p o mel os, fr uit j uices) fr o m 7 d a y s pri or t o t he first 
d ose of st u d y i nter ve nti o n u ntil c ollecti o n of t he fi nal P K bl o o d sa m ple.  

W hile partici pa nts are c o nfi ne d, t he ir t otal dail y n utriti o nal c o m p ositi o n s h o ul d be 
a p pr o xi matel y 5 5 % car b o h ydrate, 3 0 % fat, a n d 1 5 % pr otei n. T he dail y cal oric i nta ke 
per partici pa nt s h o ul d n ot e xcee d a p pr o xi mately 3 2 0 0 kcal.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 4
5. 3. 3. C affei ne, Alc o h ol, a n d T o b acc o

Partici pa nt s will a bstai n fr o m caffei ne-c o ntai ni n g pr o d ucts f or 2 4 h o urs pri or t o t he 
start of d osi n g u ntil c ollecti o n of t he fi nal P K sa m ple of eac h st u d y  peri o d.  

Partici pa nt s will a bstai n fr o m alc o h ol f or 2 4 h o urs pri or ( or as s pecifie d a b o ve f or re d 
wi ne) t o a d missi o n t o t he C R U a n d c o nti n ue a bstai ni n g fr o m alc o h ol u ntil c ollecti o n 
of t he fi nal P K sa m ple a n d fi nal E C G meas ure me nt of eac h st u d y peri o d. Partici pa nt s 
ma y  u n der g o a n alc o h ol breat h test or bl o o d alc o h ol test at t he discreti o n of t he 
i n vesti gat or.

Partici pa nt s will a bstai n fr o m t he use of t o bacc o- or nic oti ne -c o ntai ni n g pr o d ucts f or 
2 4 h o urs pri or t o d osi n g a n d d uri n g c o nfi ne me nt i n t he C R U.
5. 3. 4. Acti vit y

Partici pa nts will a bstai n fr o m stre n u o us e xerci se (e g, hea vy lifti n g, wei g ht trai ni n g, 
calist he nics, aer o bics) f or at least 4 8 h o urs pri or t o eac h bl o o d c ollecti o n f or cli nical 
la b orat or y tests. Wal ki n g at a n or mal pace will be per mitte d;

I n or der t o sta n dar dize t he c o n diti o ns o n P K sa m pli n g o n Da y  3, partici pa nt s will be 
re q uire d t o refrai n fr o m l yi n g d o w n (e xce pt w he n re q uire d f or B P, p ulse rate , a n d 
E C G meas ure me nts), eati n g, a n d dri n ki n g be vera ges ot her t ha n water d uri n g t he first 
4 h o urs after d osi n g;

F or acti vit y  restricti o ns relati n g t o E C G meas ure me nts, see Secti o n 8. 3 . 5.  
5. 4. Scree n F ail ures
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y  b ut 
are n ot s u bse q ue ntl y e nr olle d i n t he st u d y. Scree n fail ure data are c ollecte d a n d re mai n as 
s o urce a n d are n ot re p orte d o n t he C R F .
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) ma y be 
rescree ne d. 
6. S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T H E R A P Y
St u d y  i nter ve nti o ns are all pres pecifie d i n vesti gati o nal a n d n o ni n vesti gati o nal me dici nal 
pr o d ucts, me dical de vices, a n d ot her i nter ve nti o ns (e g, s ur gical a n d be ha vi oral) i nte n de d t o 
be a d mi nistere d t o t he st u d y  partici pa nts d uri n g t he st u d y c o n d uct.
F or t he p ur p oses of t his pr ot oc ol, st u d y i nter ve nti o n refers t o sis u nat o vir, matc hi n g place b o, 
a n d acti ve c o ntr ol m o xifl o xaci n .
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 5
6. 1. St u d y I nter ve nti o n(s) A d mi nistere d
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
P F - 0 7 9 2 3 5 6 8 (sis u nat o vir)
Place b o f or P F -0 7 9 2 3 5 6 8 
(sis u nat o vir)
M o xifl o xaci n
Tre at me nt Ar m
A
B
C
U nit D ose Stre n gt h(s)
5 0 m g
Place b o
4 0 0 m g
D ose F or m ul ati o n
Ca ps ule 
Ca ps ule 
Ta blet
D os a ge Le vel(s)
Pl a n ne d d oses are 
*
m g  
 f or  d oses.
0 m g  
 f or  
d oses
4 0 0 m g m o xifl o xaci n o n 
Da y 
* *
R o ute of A d mi nistr ati o n
Oral 
Oral
Oral
Use
E x peri me ntal
Place b o -c o m parat or
Acti ve -c o m parat or
I M P or NI M P/ A x M P
I M P
I M P
A x M P
S o urci n g
Pr o vi de d ce ntrall y b y t he 
s p o ns or
Pr o vi de d ce ntrall y b y t he 
s p o ns or
Pr o vi de d l ocall y b y t he 
C R U
P ac k a gi n g a n d L a beli n g
T he sis u nat o vir 5 0 m g 
ca ps ules will be pr o vi de d 
i n b ul k. C R U Staff will 
pre pare i n di vi d ual d oses 
f or a d mi nistrati o n
T he place b o ca ps ules will 
be pr o vi de d i n b ul k. C R U 
Staff will pre pare 
i n di vi d ual d oses f or 
a d mi nistrati o n
T he C R U will e ns ure t hat 
all l ocall y s o urce d 
m o xifl o xaci n ta blets t o be 
use d i n t he st u d y are fr o m 
t he sa me l ot.
S R S D
I B
I B
U S PI
C urre nt/ F or mer N a me(s) 
or Ali as(es)
Sis u nat o vir
P F -0 7 9 2 3 5 6 8
R V 5 2 1
Place b o
M o xifl o xaci n
A vel o x, Vi ga m o x, 
M o xifl o x, ot hers
* D ose will be a dj uste d t o t he hi g hest feasi ble d ose t hat is s ufficie nt well t olerate d , u p t o 
.
* * Sis u nat o vir place b o will be a d mi nistere d  
 f or  d oses, f oll o we d b y a si n gle d ose of 4 0 0 m g 
m o xifl o xaci n o n Da y .
Sis u nat o vir will be pr o vi de d b y  Pfizer as 5 0- m g  ca ps ules at t he C R U.
Matc hi n g place b o will als o be pr o vi de d.
Ca ps ules will be s u p plie d t o t he C R U i n b ul k al o n g wit h i n di vi d ual d osi n g c o ntai ners f or u nit 
d osi n g.
M o xifl o xaci n will be s u p plie d b y  t he C R U.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 6
6. 1. 1. A d mi nistr ati o n
Partici pa nts will recei ve st u d y i nter ve nti o n at a p pr o xi matel y 0 8 0 0 h o urs ( pl us or mi n us 
2 h o urs) a p pr o xi matel y 3 0 mi n utes after t he start of a sta n dar d brea kfast t hat will be 
c o ns u me d o ver a p pr o xi matel y 2 0 mi n utes. Partici pa nts will recei ve t he e ve ni n g d ose of st u dy 
i nter ve nti o n 1 2 h o urs after t he m or ni n g d ose ( pl us or mi n us 1 h o ur) a p pr o xi matel y 3 0 
mi n utes after t he start of a sta n dar d di n ner t hat will be c o ns u me d o ver a p pr o xi matel y  2 0 
mi n utes. I n all s u bse q ue nt treat me nt peri o ds, t he ti mi n g of d ose a d mi nistrati o n f or a gi ve n 
partici pa nt m ust be matc he d t o t hat of t he first peri o d ( ± 1 5 mi n utes). O n Da y 3 i n eac h peri o d 
o nl y  t he m or ni n g d ose of st u d y i nter ve nti o n will be a d mi nistere d. I n vesti gat or site pers o n nel 
will a d mi nister st u d y i nter ve nti o n d uri n g eac h peri o d wit h a m bie nt te m perat ure water t o a 
t otal v ol u me of a p pr o xi matel y 2 4 0 m L .P artici pa nt s ma y recei ve a d diti o nal a m bie nt 
te m perat ure water u p t o 1 0 0 m L, if nee de d. Partici pa nt s will s wall o w t he st u d y i nter ve nti o n
w h ole, a n d will n ot ma ni p ulate or c he w t he st u d y i nter ve nti o n pri or t o s wall o wi n g. 
I n or der t o sta n dar dize t he c o n diti o ns o n P K sa m pli n g o n Da y  3, all partici pa nt s will be 
re q uire d t o refrai n fr o m l yi n g d o w n (e xce pt w he n re q uire d f or B P, p ulse rate , a n d E C G 
meas ure me nts), eati n g, a n d dri n ki n g be vera ges ot her t ha n water d uri n g t he first 4 h o urs after 
d osi n g.
6. 2. Pre p ar ati o n , H a n dli n g , St or a ge , a n d Acc o u nt a bilit y
1.
T he i n vesti gat or or desi g nee m ust c o nfir m t hat a p pr o priate c o n diti o ns (e g, 
te m perat ure) ha ve bee n m ai ntai ne d d uri n g tra nsit f or all st u d y i nter ve nti o ns recei ve d 
a n d a n y discre pa ncies are re p orte d a n d res ol ve d bef ore use of t he st u d y i nter ve nti o n. 
2.
O nl y  partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y i nter ve nti o n a n d o nl y 
a ut h orize d site staff ma y  su p pl y , pre pare, a n d/or a d mi nister st u d y  i nter ve nti o n.
3.
All st u d y  i nter ve nti o ns m ust be st ore d i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d 
m o nit ore d ( ma n ual or a ut o mate d rec or di n g) area i n acc or da nce wit h t he la bele d 
st ora ge c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d a ut h orize d site staff. At 
a mi ni m u m, dail y mi ni m u m a n d ma xi m u m te m perat ures f or all site st ora ge l ocati o ns 
m ust be d oc u me nte d a n d a vaila ble u p o n re q uest. Data f or n o n w or ki n g da y s m ust 
i n dicate t he mi ni m u m a n d ma xi m u m te m perat ures since pre vi o usl y d oc u me nte d u p o n 
ret ur n t o b usi ness.
4.
A n y  e xc ursi o ns fr o m t he st u d y i nter ve nti o n la bel st ora ge c o n diti o ns s h o ul d be 
re p orte d t o Pfizer u p o n disc o ver y al o n g wit h acti o ns ta ke n. T he site s h o ul d acti vely 
p urs ue o pti o ns f or ret ur ni n g t he st u d y i nt er ve nti o n t o t he la bele d st ora ge c o n diti o ns, 
as s o o n as p ossi ble. O nce a n e xc ursi o n is i de ntifie d, t he st u d y  i nter ve nti o n m ust be 
q uara nti ne d a n d n ot use d u ntil Pfizer pr o vi des per missi o n t o use t he st u d y  
i nter ve nti o n. S pecific details re gar di n g t he e xc ursi o n defi niti o n a n d i nf or mati o n t o
re p ort f or eac h e xc ursi o n will be pr o vi de d t o t he site i n t he P C R U pr oce d ures.
5.
A n y  st ora ge c o n diti o ns state d i n t he S R S D will be s u perse de d b y t he st ora ge 
c o n diti o ns state d o n t he la bel.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 7
6.
St u d y  i nter ve nti o ns s h o ul d be st ore d i n t heir ori gi nal c o ntai ners.
7.
T he i n vesti gat or, i nstit uti o n, hea d of t he me dical i nstit uti o n ( w here a p plica ble), or 
a ut h orize d site staff is res p o nsi ble f or st u d y i nter ve nti o n acc o u nta bilit y, 
rec o nciliati o n, a n d rec or d mai nte na nce (ie, recei pt, rec o nciliati o n, a n d fi nal 
dis p ositi o n rec or ds) , s uc h as t he IP A L  or s p o ns or-a p pr o ve d e q ui vale nt . All st u d y  
i nter ve nti o ns will be acc o u nte d f or usi n g a st u d y i nter ve nti o n acc o u nta bilit y 
f or m/rec or d.
8.
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y  
i nter ve nti o ns are pr o vi de d i n t he P C R U’s pr oce d ures . All destr ucti o n m ust be 
a de q uatel y d oc u me nte d. If destr ucti o n is a ut h orize d t o ta ke place at t he i n vesti gat or 
site, t he i n vesti gat or m ust e ns ure t hat t he materials are destr oye d i n c o m pl ia nce wit h 
a p plica ble e n vir o n me ntal re g ulati o ns, i nstit uti o nal p olic y , a n d a n y s pecial i nstr ucti o ns 
pr o vi de d b y Pfizer.
6. 2. 1. U p o n i de ntific ati o n of a pr o d uct c o m pl ai nt, n otif y t he s p o ns or w it hi n 1 b usi ness 
d a y of disc o ver y. Pre p ar ati o n a n d Dis pe nsi n g
Wit hi n t his
pr ot oc ol, pre parati o n refers t o t he i n vesti gat or site acti vities perf or me d t o ma ke 
t he st u d y i nter ve nti o n rea d y f or a d mi nistrati o n or dis pe nsi n g t o t he partici pa nt b y  q ualifie d 
staff. Dis pe nsi n g is defi ne d as t he pr o visi o n of st u d y i nter ve nti o n, c o nc o mitant treat me nts, 
a n d acc o m pa n yi n g i nf or mati o n b y  q ualifie d staff me m ber(s) t o a healt hcare pr o vi der, 
partici pa nt , i n acc or da nce wit h t his pr ot oc ol. Local healt h a ut h orit y re g ulati o ns or 
i n vesti gat or site g ui deli nes ma y use alter nati ve ter ms f or t hese acti vities.
P F - 0 7 9 2 3 5 6 8 a n d place b o will be pre pare d b y q ualifie d u n bli n de d site pers o n nel. Bli n de d 
st u d y i nter ve nti o n will be a d mi nistere d i n a bli n de d fas hi o n t o t he partici pa nt . Ca ps ules will 
be pre pare d at t he C R U i n t he i n di vi d ual d osi n g c o ntai ners b y 2 o perat ors, 1 of w h o m is a n 
a p pr o priatel y q ualifie d a n d e x perie nce d me m ber of t he st u d y  staff (e g, p h ysicia n, n urse, 
p h y sicia n’s assista nt, n urse practiti o ner, p har mac y assista nt/tec h nicia n, or p har macist). T he 
ca ps ules will be pr o vi de d i n u nit d ose c o ntai ners a n d la bele d i n acc or da nce wit h Pfizer 
re g ulati o ns a n d t he cli nical site’s la beli n g re q uire me nts. 
6. 3. Assi g n me nt t o St u d y I n ter ve nti o n
T he i n vesti gat or’s k n o wle d ge of t he treat me n t s h o ul d n ot i nfl ue nce t he decisi o n t o e nr oll a 
partic ular partici pa nt or affect t he or der i n w hic h partici pa nts are e nr olle d. T he i n vesti gat or 
will assi g n partici pa nt n u m bers t o t he partici pa nt s as t he y are scree ne d f or t he st u d y. Pfizer 
will pr o vi de a ra n d o mizati o n sc he d ule t o t he i n vesti gat or a n d, i n acc or da nce wit h t he 
ra n d o mizati o n n u m bers, t he partici pa nt will recei ve t he st u d y  treat me nt re gi me n assi g ne d t o 
t he c orres p o n di n g ra n d o mizati o n n u m ber. A n ot her wise u ni n v ol ve d t hir d part y will be 
res p o nsi ble f or a d mi nistrati o n of t he dr u g. T his i ncl u des e ns uri n g t hat t here are n o 
differe nces i n ti me or eff ort ta ke n t o a d mi nister t he st u d y  i nter ve nti o n a n d n o bli n de d site 
staff are a ble t o vie w t he a d mi nistrati o n.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 8
6. 4. Bli n di n g
T his is a d o u ble -bli n d (s p o ns or -o pe n ) st u d y. M o xifl o xaci n a d mi nistrati o n o n Da y  3 will be 
u n bli n de d.
6. 4. 1. Bli n di n g of P a rtici p a nts
Partici pa nts will be bli n de d t o t heir assi g ne d st u d y i nter ve nti o n. M o xifl o xaci n a d mi nistrati o n
o n Da y  3 will be u n bli n de d.
6. 4. 2. Bli n di n g of Site Pers o n nel
I n vesti gat ors an d ot her site staff will be bli n de d t o partici pa nts’ assi g ne d st u d y i nter ve nti o n
f or sis u nat o vir a n d matc hi n g place b o . M o xifl o xaci n a d mi nistrati o n o n Da y  3 will be 
u n bli n de d.
Partici pa nts will be assi g ne d t o recei ve st u d y i nter ve nti o n acc or di n g t o t he assi g ne d treat me nt 
gr o u p fr o m t he ra n d o mizati o n sc he me. I n vesti gat ors will re mai n bli n de d t o eac h partici pa nt’s 
assi g ne d st u d y i nter ve nti o n f or sis u nat o vir a n d place b o t hr o u g h o ut t he c o urse of t he st u d y. 
I n or der t o mai ntai n t his bli n d, a n ot her wise u ni n v ol ve d t hir d party will be res p o nsi ble f or 
a d mi nistrati o n of sis u nat o vir a n d matc hi n g place b o . T his i ncl u des e ns uri n g t hat t here are n o 
differe nces i n ti me or eff ort ta ke n t o a d mi nister t he st u d y  i nter ve nti o n a n d n o bli n de d site 
staff are a ble t o vie w t he a d mi nistrati o n.
I n t he e ve nt of a Q uality Ass ura nce a u dit, t he a u dit or(s) will be all o we d access t o u n bli n de d 
st u d y i nter ve nti o n rec or ds at t he site(s) t o verif y t hat ra n d o mizatio n/ dis pe nsi n g has bee n d o ne 
acc uratel y.
P C R U P har mac y staff res p o nsi ble f or pre pari n g all st u d y  i nter ve nti o n will be u n bli n de d. 
P C R U site staff pr o vi di n g tec h nical s ys te m s u p p ort t o t he P har mac y staff, a n d s u p p orti n g 
bli n de d la b orat or y  data pr ocesses will be u n bli n de d. T hese site staff pr o vi di n g s ys te m 
s u p p ort are n ot i n v ol ve d i n a n y data c ollecti o n or cli nic fl o or acti vities.
6. 4. 3. Bli n di n g of t he S p o ns or
As t his is a s p o ns or -o pe n st u d y , a li mite d n u m ber of t he s p o ns or’s tea m me m bers (e xcl u di n g
site staff) ma y c o n d uct u n bli n de d re vie ws of t he data d uri n g t he c o urse of t he st u d y  f or t he
p ur p ose of safet y a n d t olera bilit y assess me nt, facilitati n g P K/ P D m o deli n g, a n d/ or s u p p orti n g
cli nical de vel o p me nt.
6. 4. 4. Bre a ki n g t he Bli n d 
T he met h o d f or brea ki n g t he bli n d i n t his st u d y will be ma n ual. I n case of a n e mer ge nc y, t he 
i n vesti gat or has t he s ole res p o nsi bilit y f or deter mi ni n g if u n bli n di n g of a partici pa nt’s 
treat me nt assi g n me nt is warra nte d. Partici pa nt safet y m ust al wa ys be t he first c o nsi derati o n 
i n ma ki n g s uc h a determi nati o n. If t he i n vesti gat or deci des t hat u n bli n di n g is warra nte d, t he 
i n vesti gat or s h o ul d ma ke e ver y eff ort t o c o ntact t he st u d y me dical m o nit or pri or t o 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4 9
u n bli n di n g a partici pa nt’s treat me nt assi g n me nt u nless t his c o ul d dela y  f urt her ma na ge me nt 
of t he pa rtici pa nt. If a partici pa nt’s treat me nt assi g n me nt is u n bli n de d, t he s p o ns or m ust be 
n otifie d wit hi n 2 4 h o urs after brea ki n g t he bli n d. W he n t he bli n di n g c o de is br o ke n, t he 
reas o n m ust be f ully d oc u me nte d i n a C R F.
Bl o o d s peci me ns will be o btai ne d fr o m al l partici pa nts f or P K a nalys is t o mai ntai n t he st u d y 
bli n d at t he i n vesti gat or site. O nl y  t he i n vesti gat or site staff a n d bli n de d st u d y m o nit or, if 
assi g ne d, will be bli n de d t o st u d y  treat me nt. Ot her Pfizer pers o n nel will be u n bli n de d t o 
partici pa nt treat m e nts i n or der t o per mit real -ti me i nter pretati o n of t he safet y a n d P K data; 
a n d pr o vi de i nf or mati o n necessar y  t o p ote ntiall y alter t he d ose-escalati o n se q ue nce. T he 
bli n de d st u d y  m o nit or, if assi g ne d, will re mai n bli n de d t o treat me nt u ntil all m o nit ori n g for 
t he st u d y has bee n c o m plete d. S peci me ns fr o m partici pa nts ra n d o mize d t o place b o will n ot 
be r o uti nel y a nal yz e d. T o mi ni mize t he p ote ntial f or bias, treat me nt ra n d o mizati o n 
i nf or mati o n will be ke pt c o nfi de ntial by Pfizer u n bli n de d pers o n nel a n d will n ot be release d 
t o t he bli n de d i n vesti gat or or bli n de d i n vesti gat or site pers o n nel u ntil t he st u d y data base has 
bee n l oc ke d or t he i n vesti gat or re q uests u n bli n di n g f or safet y reas o ns.
6. 5. St u d y I nter ve nti o n C o m pli a nce
W he n t he i n di vi d ual d ose f or a partici pa nt is pre pare d fr o m a b ul k s u p pl y , t he pre parati o n of 
t he d ose will be c o nfir me d b y a sec o n d q ualifie d me m ber of t he st u d y site staff. 
W he n partici pa nts are d ose d at t he site, t he y  will recei ve st u d y i nter ve nti o n directl y fr o m t he 
i n vesti gat or or desi g nee, u n der me dical s u per visi o n. T he date a n d ti me of eac h d ose 
a d mi nistere d i n t he cli nic will be rec or de d i n t he s o urce d oc u me nts a n d rec or de d i n t he C R F. 
T he d ose of st u d y i nter ve nti o n a n d st u d y partici pa nt i de ntificati o n will be c o nfir me d at t he 
ti me of d osi n g by a me m ber of t he st u d y site staff. St u d y  site pers o n nel will e xa mi ne eac h 
partici pa nt’s m o ut h t o e ns ure t hat t he st u d y  i nter ve nti o n was i n geste d.
6. 6. D ose M o dific ati o n
D ose m o dificati o n of sis u nat o vir is n ot all o we d. T he sis u nat o vir d ose selecte d will be t he
hi g hest feasi ble s ufficie ntl y  t olerate d d ose. I n t his st u d y, a n i nitial d ose of 
 has 
bee n selecte d t o ac hie ve hi g h cli nical e x p os ure base d o n i nter p olati o n bet wee n t he 
 m g 
a n d  
 m g e x p os ures o bser ve d i n  
. T he safety a n d P K data fr o m a p pr o xi matel y  
t he first 7 partici pa nts ma y  be assesse d a n d if o bser ve d e x p os ure of 
 is l o wer 
t ha n pre dicte d (see Ta ble 3 ) a n d d o n ot c o ver t he hi g h cli nical e x p os ure, t he n t he d ose will be 
i ncrease d t o 
.
6. 7. C o nti n ue d Access t o St u d y I nter ve nti o n A fter t he E n d of t he St u d y
N o st u d y i nter ve nti o n will be pr o vi de d t o partici pa nts at t he e n d of t heir st u d y partici pati o n.
6. 8. Tre at me nt of O ver d o se
F or t his st u d y , a n y d ose of sis u nat o vir greater t ha n 1 2 0 0 m g wit hi n a 2 4- h o ur ti me peri o d 
will be c o nsi dere d a n o ver d ose.
T here is n o s pecific treat me nt f or a n o ver d ose.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 0
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or s h o ul d:
1.
C o ntact t he st u d y me dical m o nit or wit hi n 2 4 h o urs.
2.
Cl osel y  m o nit or t he partici pa nt f or a ny A E s/ S A Es a n d la b orat or y a b n or malities as 
me dicall y  a p pr o priate a n d at least u ntil t he ne xt sc he d ule d f oll o w- u p.
3.
D oc u me nt t he q ua ntit y of t he e xcess d ose as well as t he d urati o n of t he o ver d ose i n 
t he C R F.
4.
O ver d ose is re p orta ble t o Pfizer Safet y  o nl y w he n ass oci ate d wit h a n S A E.
5.
O btai n a bl o o d sa m ple f or P K a nal ys is if re q ueste d b y t he st u d y me dical m o nit or 
( deter mi ne d o n a case-b y -case basis).
6. 9. Pri or a n d C o nc o mit a nt T her a p y
Use of presc ri pti o n or n o n prescri pti o n dr u gs a n d dietar y a n d her bal s u p ple me nts are 
pr o hi bite d wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n wit h t he e xce pti o n of a nti bi otics a n d m o derate/str o n g C Y P 3 A i n d ucers or ti me-
de pe n de nt i n hi bit ors w hic h are pr o hi bite d wit hi n 1 4 da y s pl us 5 half-li ves pri or t o t he first 
d ose of st u d y  i nter ve nti o n. Li mite d use of n o n prescri pti o n me dicati o ns t hat are n ot belie ve d 
t o affect partici pa nt safet y or t he o verall res ults of t he st u d y may be per mitte d o n a 
case-b y -case basis f oll o wi n g a p pr o val b y t he s p o ns or. Aceta mi n o p he n/ paraceta m ol ma y  be 
use d at d oses of ≤1 g/ da y.
H or m o nal c o ntrace pti ves t hat meet t he re q uire me nts of t his st u d y  are all o we d t o be use d i n 
partici pa nts w h o are W O C B P (see A p pe n di x 4 ).
All c o nc o mita nt treat me nts ta ke n d uri n g t he st u d y  m ust be rec or de d wit h i n dicati o n, dail y 
d ose, a n d start a n d st o p dates of a d mi nistrati o n. All partici pa nts will be q uesti o ne d a b o ut 
c o nc o mita nt treat me nt at eac h cli nic visit.
Treat me nts ta ke n wit hi n 2 8 da y s bef ore t he first d ose of st u d y i nter ve nti o n will be 
d oc u me nte d as a pri or treat me nt. Treat me nts ta ke n after t he first d ose of st u d y  i nter ve nti o n 
will be d oc u me nte d as c o nc o mita nt treat me nts.
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L
7. 1. Disc o nti n u ati o n of St u d y I nter ve nti o n
It ma y be necessar y f or a partici pa nt t o per ma ne ntl y disc o nti n ue st u d y i nter ve nti o n. Reas o ns 
f or per ma ne nt disc o nti n uati o n of st u d y i nter v e nti o n i ncl u de t he f oll o wi n g:

A E re q uiri n g disc o nti n uati o n i n i n vesti gat or’s vie w.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 1

Pre g na nc y .
If st u d y i nter ve nti o n is per ma ne ntly disc o nti n ue d, t he partici pa nt will n ot re mai n i n t he st u d y 
f or f urt her e val uati o n. See t he S o A f or data t o be c ollecte d at t he ti me of disc o nti n uati o n of 
st u d y i nter ve nti o n. I n t he e ve nt of disc o nti n uati o n of st u d y i nter ve nti o n, it m ust be 
d oc u me nte d o n t he a p pr o priate C R F/i n t he me dical rec or ds w het her t he partici pa nt is 
disc o nti n ui n g f urt her recei pt of st u d y  i nter ve nti o n or als o fr o m st u d y pr oce d ures, 
p osttreat me nt st u d y  f oll o w-u p, a n d/ or f ut ure c ollecti o n of a d diti o nal i nf or mati o n.
Partici pa nts w h o de vel o p a mar ke d pr ol o n gati o n of t he Q T/ Q Tc i nter val d uri n g t he 3- d a y  
c o urse wit h t he st u d y  dr u g m ust be disc o nti n ue d fr o m f urt her st u d y treat me nt a n d f oll o we d 
f or safet y, es peciall y if t he meas ure me nt is o btai ne d fr o m m ore t ha n o ne E C G. A mar ke d 
pr ol o n gati o n of t he Q T/ Q Tc i nter val is defi ne d as a Q T/ Q Tc t o > 5 0 0 ms or of > 6 0 ms o ver 
baseli ne . 
7. 2. P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al F r o m t he St u d y
A partici pa nt ma y  wit h dra w fr o m t he st u d y at a ny ti me at t heir o w n re q uest . Reas o ns f or 
disc o nti n uati o n fr o m t he st u d y  i ncl u de t he f oll o wi n g:

Ref use d f urt her st u d y pr oce d ures;

L ost t o f oll o w - u p;

Deat h;

St u d y  ter mi nate d b y s p o ns or;

Pre g na nc y ;

Be ha vi oral, c o m plia nce, or a d mi nistrati ve reas o ns.
At t he ti me of disc o nti n ui n g fr o m t he st u d y, if p ossi ble, a n earl y disc o nti n uati o n visit s h o ul d 
be c o n d ucte d. See t he S o A f or assess me nts t o be c ollecte d at t he ti me of st u d y 
disc o nti n uati o n a n d f oll o w- u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d.
T he earl y  disc o nti n uati o n visit a p plies o nl y  t o partici pa nts w h o are e nr olle d/ ra n d o mize d a n d 
t he n are pre mat urel y wit h dra w n fr o m t he st u d y . Partici pa nts s h o ul d be q uesti o ne d re gar di n g 
t heir reas o n f or wit h dra wal.
T he partici pa nt will be per ma ne ntl y disc o nti n ue d fr o m t he st u d y i nter ve nti o n a n d t he st u d y  at 
t hat ti me.
If a partici pa nt wit h dra ws fr o m t he st u d y, t he y m a y re q uest destr ucti o n of a n y re mai ni n g 
sa m ples ta ke n a n d n ot teste d, a n d the i n vesti gat or m ust d oc u me nt a n y  s uc h re q uests i n t he 
site st u d y rec or ds a n d n otif y t he s p o ns or acc or di n gl y.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 2
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt (see Secti o n 7. 2. 1 ) 
f or discl os ure of f ut ure i nf or mati o n, n o f urt her e val uati o ns will be perf or me d a n d n o 
a d diti o nal data will be c ollecte d. T he s p o ns or ma y retai n a n d c o nti n ue t o use a ny data 
c ollecte d bef ore s uc h wit h dra wal of c o nse nt.
7. 2. 1. Wit h dr a w al of C o nse nt 
Partici pa nt s w h o re q uest t o disc o nti n ue recei pt of st u d y i nter ve nti o n will re mai n i n t he st u d y  
a n d m ust c o nti n ue t o be f oll o we d f or pr ot oc ol -s pecifie d f oll o w- u p pr oce d ures. T he o nly 
e xce pti o n t o t his is w he n a partici pa nt s pecifically wit h dra ws c o nse nt f or a n y f urt her c o ntact 
wit h t he m or pers o ns pre vi o usl y  a ut h orize d b y t he partici pa nt t o pr o vi de t his i nf or mati o n. 
Partici pa nt s s h o ul d n otif y the i n vesti gat or i n writi n g of t he decisi o n t o wit h dra w c o nse nt 
fr o m f ut ure f oll o w-u p, w he ne ver p ossi ble. T he wit h dra wal of c o nse nt s h o ul d be e x plai ne d i n 
detail i n t he me dical rec or ds b y t he i n vesti gat or, as t o w het her t he wit h dra wal is o nl y  fr o m 
f urt her recei pt of st u d y i nter ve nti o n or als o fr o m st u d y  pr oce d ures a n d/ or p osttreat me nt st u d y 
f oll o w-u p, a n d e ntere d o n t he a p pr o priate C R F pa ge. I n t he e ve nt t hat vital stat us ( w het her 
t he partici pa nt is ali ve or dea d) is bei n g meas ure d, p u blicl y a vaila ble i nf or mati o n s h o ul d be 
use d t o deter mi ne vital stat us o nl y  as a p pr o priatel y directe d i n acc or da nce wit h l ocal la w.
7. 3. L ost t o F oll o w - up 
A partici pa nt will be c o nsi dere d l ost t o f oll o w- u p if t he partici pa nt re peate dl y fails t o ret ur n 
f or sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site.
T he f oll o wi n g acti o ns m ust be ta ke n if a partici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit:

T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d visit as 
s o o n as p ossi ble. Co u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d ascertai n w het her t he partici pa nt wis hes t o a n d/ or s h o ul d 
c o nti n ue i n t he st u d y;

Bef ore a parti ci pa nt is dee me d l ost t o f oll o w - u p, t he i n vesti gat or or desi g nee m ust 
ma k e e ver y eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n maili n g 
a d dress or l ocal e q ui vale nt met h o ds). T hese c o ntact atte m pts s h o ul d be d oc u me nte d 
i n t he partici pa nt’s me dical rec or d ;

S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, t he partici pa nt will be c o nsi dere d 
t o ha ve wit h dra w n fr o m t he st u d y. 
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
8. 1. A d mi nistr ati ve a n d B aseli ne Pr oce d ures
T he i n vesti gat or ( or a n a p pr o pria te dele gate at t he i n vesti gat or site) m ust o btai n a si g ne d a n d 
date d I C D bef ore perf or mi n g a n y st u d y- s pecific pr oce d ures.  
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 3
St u d y  pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A . Pr ot oc ol wai vers or 
e xe m pti o ns are n ot all o we d.
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A , is esse ntial 
a n d re q uire d f or st u d y c o n d uct.
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all e li gi bilit y criteria. T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble.
Partici pa nts will be scree ne d wit hi n 2 8 da y s pri or t o a d ministrati o n of t he st u d y  i nter ve nti o n 
t o c o nfir m t hat t he y meet t he st u d y p o p ulati o n criteria f or t he st u d y. If t he ti me bet wee n 
scree ni n g a n d d osi n g e xcee ds 2 8 d a y s as a res ult of u ne x pecte d dela ys (e g, dela ye d dr u g 
s hi p me nt), t he n partici pa nts d o n ot re q uire rescree ni n g if t he la b orat or y res ults o btai ne d pri or 
t o first d ose a d mi nistrati o n meet eli gi bilit y criteria.
A partici pa nt w h o q ualifie d f or t his pr ot oc ol b ut di d n ot e nr oll fr o m a n earlier c o h ort/ gr o u p 
ma y  be use d i n a s u bse q ue nt c o h ort wit h o ut rescree ni n g, pr o vi de d la b orat or y res ults o btai ne d 
pri or t o t he first d ose a d mi nistrati o n meet eli gi bilit y  criteria f or t his st u d y. I n a d diti o n, ot her 
cli nical assess me nts or s peci me n c ollecti o ns, e g, retai ne d researc h sa m ples, ma y be use d 
wit h o ut re peat c ollecti o n, as a p pr o priate.
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat pr ot oc ol-re q uire d tests a n d pr oce d ures are 
c o m plete d as descri be d. H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here ma y  be 
circ u msta nces o utsi de t he c o ntr ol of t he i n vesti gat or t hat ma ke it u nfeasi ble t o perf or m t he 
test. In t hese cases, t he i n vesti gat or m ust ta ke all ste ps necessar y  t o e ns ure t he safety a n d 
well -bei n g of t he partici pa nt . W he n a pr ot oc ol-re q uire d test ca n n ot be perf or me d, t he 
i n vesti gat or will d oc u me nt t he reas o n f or t he misse d test a n d a ny c orrecti ve a n d pre ve nti ve 
acti o ns t hat t he y ha ve ta ke n t o e ns ure t hat re q uire d pr ocesses are a d here d t o as s o o n as 
p ossi ble. T he st u d y  tea m m ust be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner.
Safet y /la b orat or y/a nalyt e res ults t hat ha ve bee n c ollecte d f or t he p ur p oses of t his st u d y  a n d 
c o ul d u n bli n d t he st u d y will n ot be re p orte d t o i n vesti gati ve sites or ot her bli n de d pers o n nel 
u ntil t he st u d y  has bee n u n bli n de d.
If a n I V cat heter is utilize d f or bl o o d sa m ple c ollecti o ns, E C Gs a n d vital si g n assess me nts 
(p ulse rate a n d B P) s h o ul d be c ollecte d pri or t o t he i nserti o n of t he cat heter.
F or s a m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d 
s hi p me nt i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or 
t o i nitiati o n of t he st u d y.
T he t otal bl o o d sa m pli n g v ol u me f or i n di vi d ual parti ci pa nts i n t his st u d y is a p pr o xi matel y 
1 2 0 m L . T he act ual c ollecti o n ti mes of bl o o d sa m pli n g ma y c ha n ge. A d diti o nal bl o o d 
sa m ples ma y be ta ke n f or safety assess me nts at ti mes s pecifie d b y Pfizer, pr o vi de d t he t otal 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 4
v ol u me ta ke n d uri n g t he st u d y  d oes n ot e xcee d 5 5 0 m L  d uri n g a ny peri o d of 5 6 c o nsec uti ve 
da y s.
T o pre pare f or st u d y partici pati o n, partici pa nt s will be i nstr ucte d o n t he i nf or mati o n i n t he 
Lifest y le C o nsi derati o ns secti o n 5. 3 a n d C o nc o mita nt T hera p y secti o n 6. 9 of t he pr ot oc ol.
8. 1. 1. B aseli ne Pr oce d ures 
Pla n ne d ti me p oi nts f or me dical hist or y  a n d de m o gra p hy are pr o vi de d i n t he S o A .
8. 2. Effic ac y Assess me nts
N ot a p plica ble
8. 3. S afet y Assess me nts
Pla n ne d ti me p oi nts f or all safet y  assess me nts are pr o vi de d i n t he S o A . U nsc he d ule d safet y
meas ure me nts ma y  be o btai ne d at a n y ti me d uri n g t he st u d y t o assess a n y percei ve d safet y 
iss ues.
8. 3. 1. P h ysic al E x a mi n ati o ns
A c o m plete p h y sical e xa mi nati o n will i ncl u de, at a mi ni m u m, hea d, ears, e yes, n ose, m o ut h, 
s ki n, heart a n d l u n g e xa mi nati o ns, l ym p h n o des, a n d gastr oi ntesti nal, m usc ul os keletal, a n d 
ne ur ol o gical s ys te ms. 
A brief p h y sical e xa mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of ge neral a p peara nce, 
t he res pirat or y a n d car di o vasc ular sys te ms, a n d partici pa nt -re p orte d sy m pt o ms.
P h y sical e xa mi nati o ns ma y be c o n d ucte d b y a p hysicia n, trai ne d p h ys icia n’s assista nt, or 
n urse practiti o ner as acce pta ble acc or di n g t o l ocal re g ulati o n. 
Hei g ht a n d wei g ht will als o be meas ure d a n d rec or de d as per t he S o A . F or meas uri n g wei g ht, 
a scale wit h a p pr o priate ra n ge a n d res ol uti o n is use d a n d m ust be place d o n a sta ble, flat 
s urface. Partici pa nt s m ust re m o ve s h oes, b ul k y la yers of cl ot hi n g, a n d jac kets s o t hat o nl y 
li g ht cl ot hi n g re mai ns. T he y m ust als o re m o ve t he co nte nts of t heir p oc kets a n d re mai n still 
d uri n g meas ure me nt of wei g ht. 
P h y sical e xa mi nati o n fi n di n gs c ollecte d d uri n g t he st u d y will be c o nsi dere d s o urce data a n d 
will n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. A n y u nt o war d p h ysical 
e xa mi nat i o n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d meet t he 
defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he pr ocesses i n 
Secti o ns 8. 4. 1 t o 8. 4 . 3.
8. 3. 2. Vit al Si g ns
8. 3. 2. 1. Bl o o d Press ure a n d P ulse R ate
S u pi ne B P will be meas ure d wit h t he partici pa nt ’s ar m s u p p orte d at t he le vel of t he heart a n d 
rec or de d t o t he nearest m m H g after a p pr o xi matel y 5 mi n utes of rest. T he sa me ar m 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 5
( prefera bly t he d o mi na nt ar m) will be use d t hr o u g h o ut t he st u d y. Partici pa nt s s h o ul d be 
i nstr ucte d n ot t o s pea k d uri n g meas ure me nts. 
T he sa me pr o perl y size d a n d cali brate d B P c uff will be use d t o meas ure B P eac h ti me. T he 
use of a n a ut o mate d de vice f or meas uri n g B P a n d p ulse rate is acce pta ble; h o we ver, w he n 
d o ne ma n uall y, p ulse rate will be meas ure d i n t he brac hial/ra dial arter y f or at least 
3 0 sec o n ds. W he n t he ti mi n g of t hese meas ure me nts c oi nci des wit h a bl o o d c ollecti o n, B P 
a n d p ulse rate s h o ul d be o btai ne d pri or t o t he n o mi nal ti me of t he bl o o d c ollecti o n.
A d diti o nal c ollecti o n ti mes, or c ha n ges t o c ollecti o n ti mes, of B P a n d p ulse rate will be 
per mitte d, as necessar y, t o e ns ure a p pr o priate c ollecti o n of safet y  data.
A n y  u nt o war d vital si g n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d
meet t he defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he 
pr ocesses i n Secti o ns 8. 4. 1 t o 8. 4. 3 .
8. 3. 3. Electr oc ar di o gr a ms
E C G meas ure me nts m ust be o btai ne d pri or t o vital si g ns assess me nt, bl o o d sa m ples, a n d 
pri or t o d osi n g ( n ote t hat, w here sc he d ule d at t he sa me n o mi nal ti me, t he E C G meas ure me nt 
ti me m ust be as cl ose as p ossi ble t o t he P K sa m pli n g ti me). It is i m perati ve t hat t he or der a n d 
ti mi n g of all st u d y pr oce d ures, i ncl u di n g meal a n d s nac k ti mes, be a p pr o xi matel y t he sa me 
( ± 1 5 mi n utes) acr oss all st u d y peri o ds. 
Sta n dar d 1 2-l ea d E C Gs ( wit h a 1 0- sec o n d r hyt h m stri p) s h o ul d be c ollecte d at ti mes 
s pecifie d i n t he S o A secti o n of t his pr ot oc ol usi n g a n E C G mac hi ne t hat a ut o maticall y  
calc ulates t he H R a n d meas ures P R i nter val, Q T i nter val, Q TcF, a n d Q R S c o m ple x .. All 
sc he d ule d E C Gs s h o ul d be perf or me d after t he partici pa nt has reste d q uietl y  f or at least 
5 mi n utes i n a s u pi ne p ositi o n.
S u pi ne b o d y  p ositi o n wit h full y  l o were d hea drest s h o ul d be
c o nsiste ntl y mai ntai ne d f or eac h E C G perf or me d. E n vir o n me ntal distractio ns i n t he cli nic
( T V, ra di o, c o n versati o n) a n d ot her st u dy pr oce d ures (e g, B P meas ure me nt, P K sa m pli n g)
d uri n g b ot h t he pre -E C G rest a n d t he E C G rec or di n g peri o d m ust be mi ni mize d. I n
partic ular, c ha n ges i n heart rate s h o ul d be a v oi de d.
Tri plicate 1 2 -lea d E C Gs will be o btai ne d a p pr o xi matel y  2 mi n utes a part; t he a vera ge of t he 
tri plicate E C G meas ure me nts c ollecte d bef ore d ose a d mi nistrati o n o n Da y 1 of eac h peri o d 
will ser ve as eac h partici pa nt ’s baseli ne Q TcF val ue. 3 baseli ne pre- d ose meas ure me nts are 
nee de d f or C Q T a nal y sis, t hese E C Gs will be d o ne a p pr o xi matel y 4 0 mi n, 2 5 mi n, a n d 1 0 
mi n bef ore t he pre - d ose meal. T he a vera ge of t he tri plicate E C Gs o ver t he 3 pre-d ose 
meas ure me nts (t otal of 9 E C Gs) will ser ve as eac h partici pa nt’s baseli ne Q Tc val ue. 
T o e ns ure safet y of t he partici pa nt s, a q ualifie d i n di vi d ual at t he i n vesti gat or site will ma ke 
c o m paris o ns t o baseli ne meas ure me nts. A d diti o nal E C G m o nit ori n g will occ ur if a) t he mea n 
val ue fr o m t he tri plicate meas ure me nts f or a n y p ost d ose Q Tc F i nter val is i ncrease d b y 
≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms ; or b) a n a bs ol ute Q T val ue is ≥5 0 0 ms f or a ny 
sc he d ule d E C G. If eit her of t hese c o n diti o ns occ urs, t he n a si n gle E C G meas ure me nt m ust be 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 6
re peate d at least h o url y u ntil Q TcF val ues fr o m 2 s uccessi ve E C Gs fall bel o w t he t hres h ol d 
val ue t hat tri g gere d t he re peat meas ure me nt .
If a) a p ost d ose Q Tc F i nter val re mai ns ≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms ; or b) a n 
a bs ol ute Q T val ue is ≥5 0 0 ms f or a ny sc he d ule d E C G f or greater t ha n 4 h o urs ( or s o o ner, at 
t he discreti o n of t he i n vesti gat or); or c) Q Tc F val ue get pr o gressi vel y  l o n ger, t he partici pa nt
s h o ul d u n der g o c o nti n u o us E C G m o nit ori n g. A car di ol o gist s h o ul d be c o ns ulte d if Q TcF
val ues d o n ot ret ur n t o less t ha n t he criteria liste d a b o ve after 8 h o urs of m o nit ori n g ( or 
s o o ner, at t he discreti o n of t he i n vesti gat or).
S pecial atte nti o n s h o ul d be gi ve n t o e ns ure i de ntical E C G lea d place me nt d uri n g e ver y  
meas ure me nt. I n s o me cases, it ma y be a p pr o priate t o re peat a b n or mal E C Gs t o r ule o ut 
i m pr o per lea d place me nt as c o ntri b uti n g t o a n o bser ve d E C G a b n or malit y. T he lea d t o be 
use d f or i nter val meas ure me nts s h o ul d be pre- s pecifie d; baseli ne a n d o n-treat me nt 
meas ure me nts s h o ul d be usi n g t he sa me lea d. E ver y  atte m pt s h o ul d be ma de t o use t he sa me 
E C G mac hi ne t hr o u g h o ut t he st u d y  f or a gi ve n partici pa nt .
I n t his st u dy, a se mi -a ut o mate d a p pr oac h t o E C G ac q uisiti o n will be use d. T his tec h ni q ue 
uses a c o m p uter al g orit h m f or t he i nitial place me nt of refere nce mar ks o n t he wa vef or ms t o 
n ote w here o n t he traci n g t he c o m p uter is ma ki n g its meas ure me nts. A sta n dar d se mi -
a ut o mate d al g orit h m will be use d s o t hat a li mite d n u m ber of C R U staff will re vie w 
pr o gra m -deter mi ne d i nter val o nsets a n d offsets a n d m o dif y  usi n g di gital cali pers o n t he rare 
oc casi o n w he n t his is necessar y . W here p ossi ble, t he sa me pers o n s h o ul d re vie w all E C G 
meas ure me nts f or a gi ve n partici pa nt t hr o u g h o ut t he all st u d y peri o ds. T his re vie w m ust be 
perf or me d b y a n a p pr o priatel y q ualifie d a n d bli n de d me m ber of C R U staff. Use of t his se mi-
a ut o mate d al g orit h m is desi g ne d t o f urt her i m pr o ve t he vali dit y  of t he a ut o mate d E C G 
rea d o ut by re d uci n g t he varia bilit y ass ociate d wit h i nter pretati o n of t he E C G wa vef or m. T his 
a p pr oac h ca n ha ve t he a d va nta ge of greater c o nsiste nc y  a n d re pr o d ucibilit y t ha n f ull y  ma n ual 
rea di n gs, w hile pr o vi di n g a n o p p ort u nit y t o c orrect a n y mista kes ma de by t he al g orit h mic 
met h o ds. Rece nt e vi de nce s u g gests t hat a ut o mate d tec h ni q ues are ca pa ble of detecti n g s mall 
c ha n ges i n t he Q Tc si milar t o t h ose wit h ma n ual rea di n gs a n d wit h t he sa me c o ncl usi o n. 1 0
T he fi nal E C G re p ort s h o ul d be mai ntai ne d i n t he partici pa nt’s s o urce d oc u me ntati o n a n d be 
t he fi nal i nter pretati o n of t he E C G rec or di n g. A ny cli nicall y si g nifica nt c ha n ges fr o m t he 
b aseli ne/ Da y 1 E C G ma y p ote ntiall y  be A Es (A p pe n di x 8 ) a n d s h o ul d be e val uate d f urt her, 
as cli nicall y warra nte d.
It is i m p orta nt t hat lea ds be place d i n t he sa me p ositi o ns eac h ti me i n or der t o ac hie ve precise 
E C G rec or di n gs. If a mac hi ne -rea d Q Tc val ue is pr ol o n ge d, as defi ne d a b o ve, re peat 
meas ure me nts ma y  n ot be necessar y if a q ualifie d me dical pr o vi der’s i nter pretati o n 
deter mi nes t hat t he Q Tc F val ues are i n t he acce pta ble ra n ge.
E C G val ues of p ote ntial cli nical c o ncer n are liste d i n A p pe n di x 8 .
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 7
8. 3. 4. Cli nic al S afet y L a b or at or y Assess me nts
See A p pe n di x 2 f or t he list of cli nical safety la b orat or y tests t o be perf or me d a n d t he S o A f or 
t he ti mi n g a n d fre q ue nc y. All pr ot oc ol -re q uire d la b orat or y assess me nts, as defi ne d i n 
A p pe n di x 2 , m ust be c o n d ucte d i n acc or da nce wit h t he la b orat or y ma n ual a n d t he S o A . 
U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u d y 
t o assess a ny percei ve d safet y iss ues.  
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y si g nifica nt c ha n ges occ urri n g d uri n g t he st u d y  i n t he A E secti o n of t he C R F. 
Cli nicall y  si g nifica nt a b n or mal la b orat or y test fi n di n gs are t h ose t hat are n ot ass ociate d wit h 
t he u n derlyi n g disease, u nless j u d ge d b y  t he i n vesti gat or t o be m ore se vere t ha n e x pecte d f or 
t he partici pa nt’s c o n diti o n.
All la b orat or y  tests wit h val ues c o nsi dere d cli nicall y si g nifica nt a n d a b n or mal d uri n g 
partici pati o n i n t he st u d y  or wit hi n 4 8 h o urs after t he last d ose of st u d y i nter ve nti o n s h o ul d 
be re peate d u ntil t he val ues ret ur n t o n or mal or baseli ne or are n o l o n ger c o nsi dere d cli nicall y 
si g nifica nt by t he i n vesti gat or or st u d y me dical m o nit or.
If s uc h val ues d o n ot ret ur n t o n or mal/ baseli ne wit hi n a peri o d of ti me j u d ge d reas o na ble b y 
t he i n vesti gat or, t he eti ol o g y s h o ul d be i de ntifie d an d t he s p o ns or n otifie d.
See A p pe n di x 6 f or s u g geste d acti o ns a n d f oll o w- u p assess me nts i n t he e ve nt of p ote ntial 
DI LI .
See A p pe n di x 7 f or i nstr ucti o ns f or la b orat or y testi n g t o m o nit or ki d ne y f u ncti o n a n d 
re p orti n g la b orat or y test a b n or malities.
Partici pa nt s ma y u n der g o ra n d o m uri ne dr u g testi n g at t he discreti o n of t he i n vesti gat or. 
Dr u g testi n g c o n d ucte d pri or t o d osi n g m ust be ne gati ve f or partici pa nt s t o recei ve st u d y 
i nter ve nti o n. 
8. 3. 5. C O VI D - 1 9 Specific A ssess me nts
Partici pa nts will be teste d f or C O VI D -1 9 i nfecti o n acc or di n g t o l ocal pr oce d ures .
8. 3. 6. Pre g n a nc y Testi n g 
A ser u m pre g na nc y  test is re q uire d at scree ni n g. F oll o wi n g scree ni n g, p re g na nc y tests ma y 
be uri ne or ser u m tests, a n d m ust ha ve a se nsiti vit y  of at least 2 5 mI U/ m L. Pre g na nc y  tests 
will be perf or me d i n W O C B P at t he ti mes liste d i n t he S o A . F oll o wi n g a ne gati ve pre g na nc y 
test res ult at scree ni n g, a p pr o priate c o ntrace pti o n m ust be c o m me nce d a n d a sec o n d ne gati ve 
pre g na nc y  test res ult will be re q uire d at t he baseli ne visit pri or t o t he partici pa nt’s recei vi n g 
t he st u d y i nter ve nti o n. Pre g na nc y tests will als o be d o ne w he ne ver 1 me nstr ual c ycle is 
misse d d ur i n g t he acti ve treat me nt peri o d ( or w he n p ote ntial pre g na nc y is ot her wise 
s us pecte d) a n d at t he e n d of t he st u d y. Pre g na nc y tests ma y als o be re peate d if re q ueste d by 
I RBs/ E C s or if re q uire d b y l ocal re g ulati o ns. If a uri ne test ca n n ot be c o nfir me d as ne gati ve 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 8
(e g, a n a m bi g u o us res ult), a ser u m pre g na nc y test is re q uire d. I n s uc h cases, t he partici pa nt 
m ust be e xcl u de d if t he ser u m pre g na nc y  res ult is p ositi ve.
8. 4. A d verse E ve nts , Seri o us A d verse E ve nts , a n d Ot her S afet y Re p orti n g
T he defi niti o ns of a n A E a n d a n S A E ca n be f o u n d i n A p pe n di x 3 .
A E s ma y arise fr o m sy m pt o ms or ot her c o m plai nts re p orte d t o t he i n vesti gat or b y  t he 
partici pa nt ( or, w he n a p pr o priate, b y a care gi ver, s urr o gate, or t he partici pa nt ’s le gall y 
a ut h orize d re prese ntati ve), or t he y ma y arise fr o m cli nical fi n di n gs of t he in vesti gat or or 
ot her healt hcare pr o vi ders (cli nical si g ns, test res ults, etc).
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e vents t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble t o p urs ue 
a n d o btai n a de q uate i nf or mati o n b ot h t o deter mi ne t he o utc o me a n d t o assess w het her t he 
e ve nt meets t he criteria f or classificati o n as a n S A E or ca use d t he partici pa nt t o disc o nt i n ue 
t he st u d y. (see Secti o n 7. 1 ). 
D uri n g t he acti ve c ollecti o n peri o d as descri be d i n Secti o n 8. 4. 1 , eac h partici pa nt will be 
q uesti o ne d a b o ut t he occ urre nce of A E s i n a n o nlea di n g ma n ner.
I n a d diti o n, t he i n vesti gat or ma y be re q ueste d b y Pfizer Safety t o o btai n s pecific f oll o w - u p 
i nf or mati o n i n a n e x pe dite d fas hi o n.
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or m ati o n
T he ti me peri o d f or acti vel y  eliciti n g a n d c ollecti n g AE s a n d S A Es (“acti ve c ollecti o n 
peri o d”) f or eac h partici pa nt be gi ns fr o m t he ti me t he partici pa nt pr o vi des i nf or me d c o nse nt, 
w hic h is o btai ne d bef ore u n der g oi n g a n y st u d y-relate d pr oce d ure a n d/ or recei vi n g st u d y 
i nter ve nti o n), t hr o u g h a n d i ncl u di n g a mi ni m u m of 2 8 cale n dar da ys after t he last 
a d mi nistrati o n of t he st u d y i nter ve nti o n.
F oll o w -u p b y  t he i n vesti gat or c o nti n ues t hr o u g h o ut t he acti ve c ollecti o n peri o d a n d u ntil t he 
A E or S A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or.
W he n a cli nicall y  i m p orta nt A E re mai ns o n g oi n g at t he e n d of t he acti ve c ollecti o n peri o d, 
f oll o w-u p b y  t he i n vesti gat or c o nti n ues u ntil t he A E or S A E or its se q uelae res ol ve or 
sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d Pfizer c o nc urs wit h t hat assess me nt.
F or partici pa nts w h o are scree n fail ures, t he acti ve c ollecti o n peri o d e n ds w he n scree n fail ure 
stat us is deter mi ne d.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt f or t he c ollecti o n of 
f ut ure i nf or mati o n, t he acti ve c ollecti o n peri o d e n ds w he n c o nse nt is wit h dra w n.
If a partici pa nt per ma ne ntl y disc o nti n ues or te m p oraril y disc o nti n ues st u d y i nter ve nti o n
beca use of a n A E or S A E m ust be rec or de d o n t he C R F a n d t he S A E re p orte d usi n g t he C T 
S A E Re p ort F or m.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5 9
I n vesti gat ors are n ot o bli gate d t o acti vely see k i nf or mati o n o n A Es or S A E s after t he 
partici pa nt has c o ncl u de d st u d y partici pati o n. H o we ver, if t he i n vesti gat or lear ns of a ny S A E, 
i ncl u di n g a deat h, at a ny ti me after a partici pa nt has c o m plete d t he st u d y, a n d t he y c o nsi der 
t he e ve nt t o be reas o na bl y relate d t o t he st u dy i nter ve nti o n, t he i n vesti gat or m ust pr o m ptl y  
re p ort t he S A E t o Pfizer usi n g t he C T S A E Re p ort F or m.
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer S afet y
All S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d as descri be d i n 
Secti o n 8. 4. 1 are re p orte d t o Pfizer Safet y o n t he C T S A E Re p ort F or m i m me diatel y u p o n 
a ware ness a n d u n der n o circ u msta nce s h o ul d t his e xcee d 2 4 h o urs, as i n dicate d i n 
A p pe n di x 3 . T he i n vesti gat or will s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 
2 4 h o urs of it s bei n g a vaila ble.
8. 4. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F
All n o nseri o us A Es a n d S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d,
w hic h be gi ns after o btai ni n g i nf or me d c o nse nt as descri be d i n Secti o n 8. 4 . 1, will be rec or de d 
o n t he A E secti o n of t he C R F.
T he i n vesti gat or is t o rec or d o n t he C R F all directl y  o bser ve d a n d all s p o nta ne o usl y  re p orte d 
A E s a n d S A Es re p orte d b y t he partici pa nt.
As part of o n g oi n g safet y re vie ws c o n d ucte d b y t he s p o ns or, a n y n o nseri o us A E t hat is 
deter mi ne d b y t he s p o ns or t o be seri o us will be re p orte d b y t he s p o ns or as a n S A E. T o as sist 
i n t he deter mi nati o n of case seri o us ness, f urt her i nf or mati o n ma y be re q ueste d fr o m t he 
i n vesti gat or t o pr o vi de clarit y a n d u n dersta n di n g of t he e ve nt i n t he c o nte xt of t he cli nical 
st u d y.
Re p orti n g of A Es a n d S A Es f or partici pa nts w h o fail scree ni n g are s u bject t o t he C R F 
re q uire me nts as descri be d i n Secti o n 5. 4 .
8. 4. 2.
Met h o d of Detecti n g A E s a n d S A Es
T he met h o d of rec or d i n g, e val uati n g, a n d assessi n g ca usalit y of AEs a n d S A Es a n d t he 
pr oce d ures f or c o m pleti n g a n d tra ns mitti n g S A E re p orts are pr o vi de d i n A p pe n di x 3 .
Care will be ta ke n n ot t o i ntr o d uce bias w he n detecti n g A E s a n d/ or S A Es. O pe n -e n de d a n d 
n o nlea di n g ver bal q uesti o ni n g of t he partici pa nt is t he preferre d met h o d t o i n q uire a b o ut 
A E occ urre nces.
8. 4. 3. F oll o w - Up of A E s a n d S A Es
After t he i nitial A E or S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y  f oll o w eac h 
partici pa nt at s u bse q ue nt visits/c o ntacts. F or eac h e ve nt, t he i n vesti gat or m ust p urs ue a n d 
o btai n a de q uate i nf or mati o n u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, 
or t he partici pa nt is l ost t o f oll o w- u p (as defi ne d i n Secti o n 7. 3 ).
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 0
I n ge neral, f oll o w- u p i nf or mati o n will i ncl u de a descri pti o n of t he e ve nt i n s ufficie nt detail t o 
all o w f or a c o m plete me dical assess me nt of t he case a n d i n de pe n de nt deter mi nati o n of 
p ossi ble ca usalit y . A ny i nf or mati o n rele va nt t o t he e ve nt, s uc h as c o nc o mita nt me dicati o ns 
an d ill nesses, m ust be pr o vi de d. I n t he case of a partici pa nt deat h, a s u m mar y  of a vaila ble 
a ut o ps y fi n di n gs m ust be s u b mitte d as s o o n as p ossi ble t o Pfizer Safet y. 
F urt her i nf or mati o n o n f oll o w -u p pr oce d ures is pr o vi de d i n A p pe n di x 3 .
8. 4. 4. Re g ul at or y Re p orti n g Re q uire me nts f or S A Es
Pr o m pt n otificati o n b y  t he i n vesti gat or t o t he s p o ns or of an S A E is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war d t he safet y of partici pa nts a n d t he safet y of a 
st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.
T he s p o ns or has a le gal res p o nsi bilit y  t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b o ut t he safety of a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n. T he 
s p o ns or will c om pl y  wit h c o u ntr y-s pecific re g ulat or y re q uire me nts relati n g t o safety 
re p orti n g t o t he re g ulat or y a ut h ority, I RBs / ECs , a n d i n vesti gat ors.
I n vesti gat or safet y re p orts m ust be pre pare d f or S U S A Rs acc or di n g t o l ocal re g ulat or y 
re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as necessar y.
A n i n vesti gat or w h o recei ves S U S A Rs or ot her s pecific safet y i nf or mati o n (e g, s u m mar y or 
listi n g of S A Es) fr o m t he s p o ns or will re vie w a n d t he n file it al o n g wit h t he S R S D(s) f or t he 
st u d y a n d will n otif y t he I R B/ E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
8. 4. 5. E n vir o n me nt al E x p os ure, E x p os ure D uri n g Pre g n a nc y or Bre astfee di n g, a n d 
Occ u p ati o n al E x p os ure
E n vir o n me ntal e x p os ure, occ urs w he n a pers o n n ot e nr olle d i n t he st u d y  as a partici pa nt 
recei ves u n pla n ne d direct c o ntact wit h or e x p os ure t o t he st u d y i nter ve nti o n. S uc h e x p os ure 
ma y  or ma y n ot lea d t o t he occ urre nce of a n A E or S A E. Pers o ns at ris k f or e n vir o n me ntal 
e x p os ure i ncl u de healt hcare pr o v i ders, fa mily me m bers, a n d ot hers w h o ma y be e x p ose d. A n 
e n vir o n me ntal e x p os ure ma y  i ncl u de E D P, E D B , a n d occ u pati o nal e x p os ure.
A n y  s uc h ex p os ure s t o t he st u d y i nter ve nti o n u n der st u d y  are re p orta ble t o Pfizer Safet y 
wit hi n 2 4 h o urs of i n vesti gat or a ware n ess.
8. 4. 5. 1. E x p os ure D uri n g Pre g n a nc y
A n E D P occ urs if:

A fe male partici pa nt is f o u n d t o be pre g na nt w hile recei vi n g or after disc o nti n ui n g 
st u d y i nter ve nti o n u ntil t he f oll o w -u p visit ( 2 8 -3 5 da y s after last d ose of st u d y dr u g).

A male partici pa nt w h o is recei vi n g or has disc o nti n ue d st u d y i nter ve nti o n
i nse mi nates a fe male part ner u ntil t he f oll o w -u p visit ( 2 8 -3 5 da y s after last d ose of 
st u d y dr u g) f or t he partici pa nt. 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 1

A fe male n o n partici pa nt is f o u n d t o be pre g na nt w hile bei n g e x p ose d or ha vi n g bee n 
e x p ose d t o st u d y i nter ve nti o n beca use of e n vir o n me ntal e x p os ure. Bel o w are 
e xa m ples of e n vir o n me ntal E D P :  

A fe male fa mil y  me m ber or healt hcare pr o vi der re p orts t hat s he is pre g na nt after 
ha vi n g bee n e x p ose d t o t he st u d y  i nter ve nti o n b y i n gesti o n, i n halati o n, or s ki n 
c o ntact .

A male fa mil y me m ber or healt hcare pr o vi der w h o has bee n e x p ose d t o t he st u d y  
i nter ve nti o n b y i n gesti o n, i n halati o n, or s ki n c o ntact t he n i nse mi nates his fe male 
part ner pri or t o or ar o u n d t he ti me of c o nce pti o n .
T he i n vesti gat or m ust re p ort E D P t o Pfizer Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nitial i nf or mati o n s u b mitte d 
s h o ul d i ncl u de t he a ntici pate d date of deli ver y  (see bel o w f or i nf or mati o n relate d t o 
ter mi nati o n of pre g na nc y). 

If E D P occ urs i n a partici pa nt/partici pa nt’s part ner, t he i n vesti gat or m ust re p ort t his 
i nf or mati o n t o Pfizer Safet y  o n t he C T S A E Re p ort F or m a n d a n E D P S u p ple me ntal 
F or m, re gar dle ss of w het her a n S A E has occ urre d. Details of t he pre g na nc y will be 
c ollecte d after t he start of st u d y  i nter ve nti o n a n d u ntil f oll o w-u p visit ( 2 8 -3 5 da y s 
after last d ose of st u d y dr u g) f or t he partici pa nt.

If E D P occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, t he i n vesti gat or m ust re p ort 
i nf or mati o n t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m a n d E D P S u p ple me ntal 
F or m. Si nce t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n 
t he st u d y, t he i nf or mati o n is n ot rec or de d o n a C R F; h o we ver, a c o py of t he 
c o m plete d C T S A E Re p ort F or m is mai ntai ne d i n t he i n vesti gat or site file.
F oll o w -u p is c o n d ucte d t o o btai n ge neral i nf or mati o n o n t he pre g na nc y  a n d its o utc o me f or 
all E D P re p orts wit h a n u n k n o w n o utc o me. T he i n vesti gat or will f oll o w t he pre g na nc y u ntil 
c o m pleti o n ( or u ntil pre g na nc y  ter mi nati o n) a n d n otif y Pfizer Safety of t he o utc o me as a 
f oll o w-u p t o t he i nitial E D P S u p ple me ntal F or m. I n t he case of a li ve birt h, t he str uct ural 
i nte grity of t he ne o nate ca n be assesse d at t he ti me o f birt h. I n t he e ve nt of a ter mi nati o n, t he 
reas o n(s) f or ter mi nati o n s h o ul d be s pecifie d a n d, if cli nicall y p ossi ble, t he str uct ural 
i nte grity of t he ter mi nate d fet us s h o ul d be assesse d b y gr oss vis ual i ns pecti o n ( u nless 
pre pr oce d ure test fi n di n gs are c o n cl usi ve f or a c o n ge nital a n o mal y a n d t he fi n di n gs are 
re p orte d).
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 2
A b n or mal pre g na nc y  o utc o mes are c o nsi dere d S A Es. If t he o utc o me of t he pre g na nc y meets 
t he criteria f or a n S A E (ie, ect o pic pre g na nc y, s p o nta ne o us a b orti o n, i ntra uteri ne fetal 
de mise, ne o nat al deat h, or c o n ge nital a n o mal y i n a li ve -b or n ba b y, a ter mi nate d fet us, a n 
i ntra uteri ne fetal de mise, or a ne o natal deat h), t he i n vesti gat or s h o ul d f oll o w t he pr oce d ures 
f or re p orti n g S A Es. A d diti o nal i nf or mati o n a b o ut pre g na nc y o utc o mes t hat are re p orte d t o 
Pfizer Safet y  as S A Es f oll o ws: 

S p o nta ne o us a b orti o n i ncl u d i n g miscarria ge a n d misse d a b orti o n s h o ul d be re p orte d 
as a n S A E ;

Ne o natal deat hs t hat occ ur wit hi n 1 m o nt h of birt h s h o ul d be re p orte d, wit h o ut re gar d 
t o ca usalit y, as S A Es. I n a d diti o n, i nfa nt deat hs after 1 m o nt h s h o ul d be re p orte d as 
S A Es w he n t he i n vesti gat or assesses t he i nfa nt deat h as relate d or p ossi bl y  relate d t o 
e x p os ure t o t he st u d y i nter ve nti o n. 
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y  be re q ueste d b y t he s p o ns or. F urt her 
f oll ow- u p of birt h o utc o mes will be ha n dle d o n a case- b y -case basis (e g, f oll o w- u p o n 
preter m i nfa nts t o i de ntif y de vel o p me ntal dela y s). In t he case of pater nal e x p os ure, t he 
i n vesti gat or will pr o vi de t he partici pa nt wit h t he Pre g na nt Part ner Release of I nf or mati o n 
F or m t o deli ver t o his part ner. T he i n vesti gat or m ust d oc u me nt i n t he s o urce d oc u me nts t hat 
t he partici pa nt was gi ve n t he Pre g na nt Part ner Release of I nf or mati o n F or m t o pr o vi de t o his 
part ner.
8. 4. 5. 2. E x p os ure D uri n g Bre astfee di n g
A n E D B occ urs if:

A fe male partici pa nt is f o u n d t o be breastfee di n g w hile recei vi n g or after 
disc o nti n ui n g st u d y  i nter ve nti o n.

A fe male n o n partici pa nt is f o u n d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g 
bee n e x p ose d t o st u d y  i nter ve nti o n (ie, e n vir o n me ntal e x p os ure). A n e xa m ple of 
e n vir o n me ntal E D B is a fe male fa mily me m ber or healt hcare pr o vi der w h o re p orts 
t hat s he is breastfee di n g after ha vi n g bee n e x p ose d t o t he st u d y i nter ve nti o n b y 
i n gesti o n, i n halati o n, or s ki n c o ntact.  
T he i n vesti gat or m ust re p ort E D B t o Pfizer Safety wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nf or mati o n m ust be re p orte d 
usi n g t he C T S A E Re p ort F or m. W he n E D B occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, 
t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n t he st u d y, s o t he 
i nf or mati o n is n ot rec or de d o n a C R F. H o we ver, a c o p y  of t he c o m plete d C T S A E Re p ort 
F or m is mai ntai ne d i n t he i n vesti gat or site file.
A n E D B re p ort is n ot create d w he n a Pfizer dr u g s pecifically a p pr o ve d f or use i n 
breastfee di n g w o me n (e g, vita mi ns) is a d mi nistere d i n acc or d a nce wit h a ut h orize d use. 
H o we ver, if t he i nfa nt e x perie nces a n S A E ass ociate d wit h s uc h a dr u g, t he S A E is re p orte d 
t o get her wit h t he E D B .
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 3
8. 4. 5. 3. Occ u p ati o n al E x p os ure
T he i n vesti gat or m ust re p ort a n y i nsta nce of occ u pati o nal e x p os ure t o Pfizer Safety wit hi n 2 4 
h o urs of t he i n vesti gat or’s a ware ness usi n g t he C T S A E Re p ort F or m re gar dless of w het her 
t here is a n ass ociate d S A E. Si nce t he i nf or mati o n a b o ut t he occ u pati o nal e x p os ure d oes n ot 
pertai n t o a partici pa nt e nr olle d i n t he st u d y, t he i nf or mati o n is n ot rec or de d o n a C R F; 
h o we ver, a c o p y of t he c o m plete d C T S A E Re p ort F or m m ust be mai ntai ne d i n t he 
i n vesti gat or site file.
8. 4. 6. C ar di o v asc ul ar a n d De at h E ve nts
N ot a p plica ble
8. 4. 7. Dise ase -Rel ate d E ve nts a n d/ or Dise ase -Rel ate d O utc o mes N ot Q u alif yi n g as A E s 
or S A Es
N ot a p plica ble
8. 4. 8. A d verse E ve nts of S peci al I nterest
N ot a p plica ble
8. 4. 8. 1. L ac k of Effic ac y
T his secti o n is n ot a p plica ble beca use efficac y  is n ot e x pecte d i n t he st u d y p o p ulati o n.  
8. 4. 9. Me dic al De vice Deficie ncies
N ot a p plica ble
8. 4. 1 0. Me dic ati o n Err ors
Me dicati o n err ors ma y  res ult fr o m t he a d mi nistrati o n or c o ns u m pti o n of t he st u d y 
i nter ve nti o n b y  t he wr o n g partici pa nt , or at t he wr o n g ti me, or at t he wr o n g d osa ge stre n gt h.
Me dicati o n err ors are rec or de d a n d re p orte d as f oll o ws:
Rec or de d o n t he 
Me dic ati o n Err or P a ge 
of t he C R F
Rec or de d o n t he 
A d verse E ve nt P a ge 
of t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfizer 
S afet y Wit hi n 2 4 H o urs of 
A w are ness
All (re gar dless of w het her 
ass ociate d wit h a n A E)
A n y  A E or S A E ass ociate d 
wit h t he me dicati o n err or
O nl y  if ass ociate d wit h a n 
S A E
Me dicati o n err ors i ncl u de:

Me dicati o n err ors i n v ol vi n g partici pa nt e x p os ure t o t he st u d y i nter ve nti o n;

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat d o 
or d o n ot i n v ol ve t he st u d y partici pa nt .
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 4
Ot her e xa m ples i ncl u de, b ut are n ot li mite d t o:

T he a d mi nistrati o n of e x pire d st u d y  i nter ve nti o n;

T he a d mi nistrati o n of a n i nc o rrect st u d y i nter ve nti o n;

T he a d mi nistrati o n of a n i nc orrect d osa ge;

T he a d mi nistrati o n of st u d y  i nter ve nti o n t hat has u n der g o ne te m perat ure e xc ursi o n 
fr o m t he s pecifie d st ora ge ra n ge, u nless it is deter mi ne d b y t he s p o ns or t hat t he st u d y 
i nter ve nti o n u n der q uesti o n is acce pta ble f or use.
S uc h me dicati o n err ors occ urri n g t o a st u d y partici pa nt are t o be ca pt ure d o n t he me dicati o n 
err or pa ge of t he C R F, w hic h is a s pecific versi o n of t he A E pa ge.
W het her or n ot t he me dicati o n err or is acc o m pa nie d b y  a n A E, as deter mi ne d b y t he 
i n vesti gat or, t he me dicati o n err or is rec or de d o n t he me dicati o n err or pa ge of t he C R F a n d, if 
a p plica ble, a n y ass ociate d A E(s), seri o us a n d n o nseri o us, are rec or de d o n t he A E pa ge of t he 
C R F.
I n t he e ve nt of a me dicati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d wit hi n 2 4 h o urs .
Me dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y wit hi n 2 4
h o urs o n a C T S A E Re p ort 
F or m o nl y w he n ass oci ate d wit h a n S A E.
8. 5. P h ar m ac o ki netics 
Bl o o d sa m ples of a p pr o xi matel y  2 m L , t o pr o vi de a p pr o xi matel y of 0. 8 m L of plas ma, will 
be c ollecte d f or meas ure me nt of plas ma c o nce ntrati o ns of sis u nat o vir as s pecifie d i n t he S o A . 
W h ole bl o o d (a p pr o xi matel y  2 m L ) will c ollecte d at 5 a n d 1 2 h o ur p ost -d ose f or i n viv o
bl o o d/ plas ma rati o assess m e nt. E x pl orat or y P K bl o o d sa m ples f or t he meas ure me nt of 
sis u nat o vir c o nce ntrati o ns will be c ollecte d, i n or der t o e val uate micr o sa m pli n g P K 
a p pr oac h usi n g t he Tass o ® micr o sa m pli n g de vice. T otal bl o o d v ol u me f or e x pl orat or y  P K 
will n ot e xcee d 0. 1 m L  at eac h ti me p oi nt s pecifie d i n t he S o A . I nstr ucti o ns f or t he c ollecti o n 
a n d ha n dli n g of bi ol o gical sa m ples will be pr o vi de d i n t he la b orat or y ma n ual or b y  t he 
s p o ns or. T he act ual date a n d ti me ( 2 4-h o ur cl oc k ti me) of eac h sa m ple will be rec or de d.
T he act ual ti mes ma y  c ha n ge, b ut t he n u m ber of sa m ples will re mai n t he sa me. All eff orts 
will be ma de t o o btai n t he sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g. C ollecti o n of 
sa m ples u p t o a n d i ncl u di n g 1 0 h o urs after d ose a d mi nistrati o n t hat are o btai ne d wit hi n 
1 0 % of t he n o mi nal ti me relati ve t o d osi n g (e g, wit hi n 6 mi n utes of a 6 0 - mi n ute sa m ple) will 
n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he c ollecti o n is n ote d o n 
t he s o urce d oc u me nt a n d t he C R F. C ollecti o n of sa m ples m ore t ha n 1 0 h o urs after d ose
a d mi nistrati o n t hat are o btai ne d ≤1 h o ur a wa y  fr o m t he n o mi nal ti me relati ve t o d osi n g will 
n ot be ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he c ollecti o n is n ote d o n 
t he s o urce d oc u me nt a n d t he C R F. T his pr ot oc ol de viati o n wi n d o w d oes n ot a p pl y  t o sa m ples 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 5
t o be c ollecte d m ore t ha n 1 0 h o urs after d ose a d mi nistrati o n at o ut patie nt/f oll o w -u p visits 
wit h visit wi n d o ws.
Sa m ples will be use d t o e val uate t he P K of sis u nat o vir. Sa m ples c ollecte d f or a nal ys es of 
plas ma c o nce ntrati o n ma y als o be use d t o e val uate safet y or efficac y as pects relate d t o 
c o ncer ns arisi n g d uri n g or after t he st u d y , f or meta b olite i de ntificati o n a n d/ or e val uati o n of 
t he bi oa nalyt ical met h o d, or f or ot her i nternal e x pl orat or y  p ur p oses.
Ge netic a nal ys es will n ot be perf or me d o n t hese plas ma sa m ples. Partici pa nt c o nfi de ntialit y  
will be mai ntai ne d.
T he P K sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns pr o vi de d t o 
t he i n vesti gat or site t o maintai n sa m ple i nte grit y . A n y  de viati o ns fr o m t he P K sa m ple 
ha n dli n g pr oce d ure (e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, i nteri m st ora ge or s hi p pi n g 
c o n diti o ns), i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or. 
O n a case -b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n as t o w het her sa m ple 
i nte grity has bee n c o m pr o mise d.
Dr u g c o nce ntrati o n i nf or mati o n t hat ma y  u n bli n d t he st u d y will n ot be re p orte d t o 
i n vesti gator sites or bli n de d pers o n nel u ntil t he st u d y has bee n u n bli n de d.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u dy assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he 
s p o ns or a n d site st u d y files, b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt. T he IR B/ E C will 
be i nf or me d of a n y safet y iss ues t hat re q uire alterati o n of t he safet y m o nit ori n g sc he me or 
a me n d me nt of t he I C D.
8. 6. Ge netics
8. 6. 1. S pecifie d Ge netics
S pecifie d g e netic a nal ys es are n ot e val uate d i n t his st u d y .
8. 7. Bi o m ar kers
Bi o mar kers are n ot e val uate d i n t his st u d y.
8. 8. I m m u n o ge nicit y Assess me nts
I m m u n o ge nicity assess me nts are n ot i ncl u de d i n t his st u d y .
8. 9. He alt h Ec o n o mics
Healt h ec o n o mics/m e dical res o urce u tilizati o n a n d h ealt h ec o n o mics para meters are n ot 
e val uate d i n t his st u d y.
9. S T A TI S TI C A L C O N SI D E R A TI O N S
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nalys es of t he data c ollecte d i n t his st u d y  
is o utli ne d here a n d will be f urt her detaile d i n t he S A P, w hic h will be mai ntai ne d b y  t he 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 6
s p o ns or. T he S A P ma y m o dif y w hat is o utli ne d i n t he pr ot oc ol w here a p pr o priate; h o we ver, 
a n y maj or m o dificati o ns of t he pri mar y e n d p oi nt defi niti o ns or t heir a nalys es will als o be 
reflecte d i n a pr ot oc ol a me n d me nt.
9. 1. St atistic al H y p ot hesis
9. 1. 1. Pri m ar y E n d p oi nt
C o nce ntrati o n -Q Tc a nal ysis will be use d t o assess if sis u nat o vir at ma xi m u m c o nce ntrati o ns 
( Cma x ) at t he 
has cli nicall y rele va nt effect o n t he Q Tc i nter val at o ne 
si de d α = 0. 0 5 le vel wit h o ut m ulti plicit y  a dj ust me nt. After a fi nal c o nce ntrati o n‑Q Tc m o del 
has bee n esta b lis he d, de n ote t he p o p ulati o n mea n of m o del pre dicte d place b o -c orrecte d 
Δ Q Tc F ( Δ Δ Q Tc F) at t he C ma x of a d ose of i nterest as µ c na x, t he n ull h yp ot hesis of sis u nat o vir
ha vi n g a p ositi ve Q Tc effect a n d t he alter nati ve h y p ot hesis of sis u nat o vir ha vi n g a ne gati ve 
Q Tc effect at t he d ose of i nterest ca n be e x presse d as t he f oll o wi n g:
H 0: µc ma x  ≥ 1 0 msec
H a: µ c ma x < 1 0 msec
T he lac k of effect of sis u nat o vir o n Q Tc i nter vals will be c o ncl u de d if t he u p per b o u n d of t he 
2 ‑si de d 9 0 % CI f or t he Q Tc F esti mate d b y t he fi nal c o nce ntrati o n‑Q Tc m o del is < 1 0 
msec at t he hi g hest cli nicall y  rele va nt e x p os ure.  
9. 1. 2. Ass a y Se nsiti vit y 
T he assa y  se nsiti vit y is teste d at 3, 4 a n d 5 - h o urs p ose -d ose of p ositi ve c o ntr ol, m o xifl o xaci n ,
o n Da y  3 si m ulta ne o usl y at o ne-si de d α = 0. 0 5 le vel wit h B o nfer o n ni c orrecti o n of α/ 3 f or 
m ulti ple assess me nts . De n ote t he p o p ulati o n mea n of c ha n ge fr o m baseli ne i n Q Tc F of 
m o xi fl o xaci n a n d place b o at 3, 4, or 5-hr p ost -d ose as µ( M) a n d µ( P), res pecti vely, t he
statistical h yp ot heses are:
H 0: μ( M) - μ( P) ≤5 msec
H a: μ( M) - μ( P) > 5 msec
T he st u d y  will be dee me d a de q uatel y se nsiti ve t o detect Q T/ Q Tc pr ol o n gati o n if a n y of t he 
l o wer li mits of t he t w o -si de d B o nferr o ni -a dj uste d 9 0 % CI ( 9 6. 7 % CI ) f or mea n differe nces
bet wee n m o xifl o xaci n a n d place b o at a n y of t he 3 , 4 a n d 5- hr p ose -d ose , res pecti vel y, are
greater t ha n 5 msec .  
9. 2. A n al ysis Sets
F or p ur p oses of a nal y sis, t he f oll o wi n g a nal ys is sets are defi ne d:
P artici p a nt A n al ysis 
Set
Descri pti o n
E nr olle d 
“E nr olle d ” mea ns a partici pa nt ’s, or t heir le gall y a ut h orize d 
re prese ntati ve’s, a gree me nt t o partici pate i n a cli nical st u d y 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 7
P artici p a nt A n al ysis 
Set
Descri pti o n
f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d 
ra n d o mizati o n. A partici pa nt will be c o nsi dere d e nr olle d if t he 
i nf or me d c o nse nt is n ot wit h dra w n pri or t o partici pati n g i n an y  
st u d y acti vity after scree ni n g. P ote ntial partici pa nts w h o are 
scree ne d f or t he p ur p ose of deter mi ni n g eli gi bilit y f or t he 
st u d y, b ut d o n ot partici pate i n t he st u d y, are n ot c o nsi dere d 
e nr olle d, u nless ot her wise s pecifie d b y t he pr ot oc ol.
E C G a nal ys is set
All partici pa nts ra n d o mize d a n d treate d w h o ha ve at least 1 
p ost -d ose E C G meas ure me nt i n at least 1 peri o d. A nal y sis sets 
ma y  c o ntai n differe nt n u m bers of partici pa nts f or differe nt 
E C G para meters base d o n a vaila bilit y of data. Partici pa nts will 
be a nal yz e d acc or di n g t o t he pr o d uct t he y  act uall y recei ve d.
C o nce ntrati o n -Q Tc 
a nal ys is set
T he c o nce ntrati o n Q Tc a nal y sis p o p ulati o n is defi ne d as all 
partici pa nts ra n d o mize d a n d treate d wit h sis u nat o vir or place b o 
w h o ha ve at least 1 pair of ti me -matc he d p ost - d ose Q T a n d 
sis u nat o vir plas ma c o nce ntrati o n val ues i n at least 1 peri o d of 
t he st u d y. F or place b o treat me nt, t he c o nce ntrati o n of is set t o 
0.
P K C o nce ntrati o n 
anal ys is set 
All partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n a n d 
w h o ta ke at least 1 d ose of st u d y  i nter ve nti o n a n d i n w h o m at 
least 1 c o nce ntrati o n val ue ca n be re p orte d.
P K Para m eter a nal ys is 
set 
All partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n a n d 
w h o ta ke at least 1 d ose of st u d y  i nter ve nti o n a n d i n w h o m at 
least 1 of t he P K para meters of i nterest ca n be re p orte d.
Safet y anal ys is set
All partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n a n d 
w h o ta ke at least 1 d ose of st u d y i nter ve nti o n. Partici pa nts will 
be a nal yz e d acc or di n g t o t he pr o d uct t he y act uall y recei ve d.
9. 3. St atistic al A n al yses
T he S A P will be de vel o pe d a n d fi nalize d bef ore a n y a nalys es are p erf or me d a n d will 
descri be t he a nal ys es a n d pr oce d ures f or acc o u nti n g f or missi n g, u n use d, a n d s p uri o us data.
T his secti o n is a s u m mar y of t he pla n ne d statistical a nal y ses of t he pri mar y a n d sec o n dar y 
e n d p oi nts.
9. 3. 1. Ge ner al C o nsi der ati o ns
Details of t he a nal y ses will be pr o vi de d i n t he S A P .
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 8
9. 3. 1. 1. Deri v ati o n of E C G P ar a meters Pri or t o A n al yses
T he a vera ge of t he tri plicate E C Gs c ollecte d at eac h ti me p oi nt acc or di n g t o t he S o A will be 
calc ulate d a n d use d i n P K/ P D m o deli n g, statistical a nal ys es, a n d/ or descri pti ve s u m maries. 
T he Q Tc F is defi ne d as Fri dericia’s heart rate c orrecti o n, o btai ne d usi n g t he f or m ula:

Q Tc F ( msec) = Q T ( msec)/( R R) 1/ 3  w here R R(sec) = 6 0/ H R (if n ot pr o vi de d)
T he Q Tc B is t he Bazett’s heart rate c orrecti o n, o btai ne d usi n g t he f or m ula:

Q Tc B( msec) = Q T( msec)/( R R) ½      w here R R(sec) = 6 0/ H R (if n ot pr o vi de d)
T he baseli ne of E C G para meters will be defi ne d as t he mea n of t he 3 a vera ges of t he
tri plicate meas ure me nts ta ke n at t he f oll o wi n g 3 ti me p oi nts (a p pr o xi matel y 4 0 mi n, 2 5 mi n, 
a n d 1 0 mi n bef ore pre-d ose meal) bef ore d osi n g o n Da y  1 wit hi n eac h peri o d. C ha n ges fr o m 
baseli ne E C G para meters , i ncl u di n g c ha n ges fr o m baseli ne i n Q Tc F, u nc orrecte d Q T, Q Tc B , 
P R, Q R S, a n d heart rate , will be calc ulate d f or eac h partici pa nt a n d treat me nt at eac h p ost -
d ose ti me p oi nt o n Da y  3 a n d 4 wit hi n eac h peri o d.
T he ma xi m u m a bs ol ute p ost- d ose val ue a n d t he ma xi m u m i ncrease fr o m baseli ne f or Q Tc F, 
Q Tc B, P R, a n d Q R S i nter vals will be deter mi ne d f or eac h partici pa nt a n d treat me nt. W he n 
t here is n o i ncrease fr o m baseli ne o ver t he res pecti ve peri o d, t he mi ni m u m decrease will be 
ta ke n.
9. 3. 1. 2. E C G D at a S u m m aries
Mea n baseli ne a n d c ha n ges fr o m baseli ne f or Q Tc F, Q Tc B, Q T ( u nc orrecte d), P R, Q R S a n d 
heart rate will be calc ulate d f or eac h partici pa nt a n d s u m marize d descri pti vel y  ( N, mea n, 
sta n dar d de viati o n [ S D], me dia n, mini m u m a n d ma xi m u m) b y  treat me nt a n d ti me p ost d ose.
Place b o -c orrecte d c ha n ge fr o m baseli ne f or Q Tc F, Q T ( u nc orrecte d) a n d heart rate 
differe nces will be s u m marize d ( N, mea n, 9 0 % CI) a n d pl otte d ( mea n) f or eac h treat me nt a n d 
ti me p oi nt p ost d ose.
Cate g oriza ti o n of H R, Q R S, a n d P R i nter vals will be descri be d i n t he S A P. Cate g orizati o n of 
ma xi m u m Q Tc will be pr o vi de d f or Q Tc F b y treat me nt usi n g t he f oll o wi n g criteri o n.
A bs ol ute Ma xi m u m ( msec)
< 4 5 0 
4 5 0 t o 
< 4 8 0 
4 8 0 t o 
< 5 0 0 
≥5 0 0 
Ma xi m u m I ncrease fr o m Baseli ne 
( msec)
< 3 0 
3 0 t o < 6 0 
> 6 0 
If a ny of t he 3 i n di vi d ual E C G traci n gs has a Q Tc F val ue 5 0 0 msec, b ut t he mea n of t he 
tri plicates is < 5 0 0 msec, t he data fr o m t he partici pa nt ’s i n di vi d ual traci n g will be descri be d 
i n a safety secti o n of t he st u d y  re p ort i n or der t o place t he 5 0 0 msec val ue i n a p pr o priate 
cli nical c o nte xt.  H o we ver, val ues fr o m i n di vi d ual traci n gs wit hi n tri plicate meas ure me nts 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 6 9
t hat are 5 0 0 msec will n ot be i ncl u de d i n t he cate g orical a nal ys es u nless t he a vera ge fr o m 
t he tri plicate meas ure me nts is als o 5 0 0 msec.  
9. 3. 2. Pri m ar y E n d p oi nt A n al ysis 
P K/ P D m o del will be esta blis he d t o c haracterize t he relati o ns hi p bet wee n sis u nat o vir plas ma 
c o nce ntrati o n a n d c ha n ge fr o m baseli ne i n Fri dericia’s heart -rate c orrecte d Q T i nter val 
( Δ Q Tc F) usi n g t he c o nce ntr ati o n-Q Tc a nal ys is set. Base d o n t he rec o m me n dati o n i n t he 
W hite Pa per
1 1, t he li near mi xe d effect m o del preferre d is pre-s pecifie d as:
∆       =   +  , +      + (   +  , )    +       +        −    +    Δ Q Tc F ij k is t he c ha n ge fr o m baseli ne i n Q TcF f or partici pa nt i i n treat me nt j at ti me k; θ0 is 
t he p o p ulati o n mea n i nterce pt i n t he a bse nce of a treat me nt effect; η0,i is t he ra n d o m effect 
ass ociate d wit h t he i nterce pt ter m θ 0; θ1 is t he fi xe d effect ass ociate d wit h treat me nt T R Tj ( 0 
= place b o, 1 = sis u nat o vir); θ2 is t he p o p ulati o n mea n sl o pe of t he ass u me d li near ass ociati o n 
bet wee n plas ma sis u nat o vir c o nce ntrati o n a n d Δ Q Tc F ij k; η1 ,i is t he ra n d o m effect ass ociate d 
wit h t he sl o pe θ 2; Cij k is t he plas ma c o nce ntrati o n of sis u nat o vir f or partici pa nt i i n treat me nt 
j a n d ti me k a n d C ij k = 0 f or place b o gr o u p ; θ3 is t he fi xe d effect ass ociate d wit h ti me; a n d θ4
is t he fi xe d effect ass ociate d wit h ce ntere d baseli ne Q Tc F ij 0, w here     is o verall mea n of 
Q Tc F ij 0, i.e., t he mea n of all t he baseli ne ( = ti me 0) Q TcF val ues. It is ass u me d t he ra n d o m 
effects ( η0,i, η1,i) are n or mall y distri b ute d wit h mea n [ 0, 0] a n d a n u nstr uct ure d c o varia nce 
matri x, w hereas t he resi d uals ε ij k are n or mall y distri b ute d wit h mea n 0 a n d varia nce σ 2.
T he m o del -deri ve d mea n Δ Δ Q Tc F a n d c orres p o n di n g t w o -si de d 9 0 % CIs will be c o m p ute d 
at c o nce ntr ati o ns of i nterests e g, e x pecte d C ma x at t he 
. If t he u p per 
b o u n d of t he t w o -si de d 9 0 % i nter val f or t he Δ Δ Q TcF as esti mate d b y t he fi nal c o nce ntrati o n-
Δ Q Tc m o del esta blis he d i n t his st u d y  is < 1 0 msec at t he hi g hest cli nicall y rele va nt e x p os ure, 
t he a bse nce of a n effect of sis u nat o vir o n Q Tc will be c o ncl u de d. T he hi g hest cli nicall y  
rele va nt e x p os ure ( d ue t o i ntri nsic a n d/ or e xtri nsic fact ors) will be deter mi ne d later fr o m 
ot her st u dies.
Details of t he m o delli n g a p pr oac h i ncl u di n g t he s tr uct ural m o del, ass u m pti o ns, criteria f or 
m o del selecti o n a n d e val uati o n as well as p ote ntial c ha n ges t o t he pre -s pecifie d m o del, if 
nee de d base d o n c o nstrai nts of t he a vaila ble data, will be descri be d i n t he S A P.
T he m o deli n g o ut p ut will be re p orte d as s ta n d-al o ne re p ort or wit hi n s pecific secti o ns i n t he 
cli nical st u d y re p ort. T he i nf or mati o n t o be re p orte d will be o utli ne d i n t he S A P.
9. 3. 3. Sec o n d ar y E n d p oi nt s A n al ysis 
C ha n ge fr o m baseli ne i n Q Tc F i nter vals will be a nal y ze d usi n g a M M R M m o del wit h 
se q ue nce, peri o d, treat me nt, ti me ( p ost-d ose ti me p oi nt) a n d treat me nt b y ti me i nteracti o n as 
fi xe d effects, partici pa nts as a ra n d o m effect, a n d baseli ne Q Tc F as t he c o variate. A 
c o m p o u n d s ym metr y  c o varia nce matri x will be fitte d t o t he re peate d ti mes wit hi n partici pa nt
( ot her c o varia nce matrices will be c o nsi dere d if necessar y), a n d t he Ke n war d-R o ger 
a p pr o xi mati o n will be use d f or esti mati n g de grees of free d o m. T he E C G a nal y sis set will be 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 0
use d f or t he M M R M a nal ysis. T he l o wer li mit of t he B o nferr o ni -a dj uste d 9 0 % CI (9 6. 7 % CI )
of mea n differe nce of m o xifl o xaci n o ver place b o at 3 , 4, a n d 5-hr p ost -d ose will be re p orte d 
se paratel y a n d c o m pare d t o t he t hres h ol d of 5 msec .
See Secti o n 9. 3. 4 f or t he sec o n dar y e n d p oi nts of safety a nal yses.
9. 3. 4. S afet y a n al yses
All safet y a nal ys es will be perf or me d o n t he Safet y  A nal ysis Set as defi ne d i n Secti o n 9. 2 .
A Es, E C Gs, B P, heart rate , c o nti n u o us car diac m o nit ori n g, a n d safety la b orat or y data, as 
a p plica ble, will be re vie we d a n d s u m marize d o n a n o n g oi n g basis d uri n g t he st u d y  t o 
e val uate t he safet y of partici pa nts. A n y cli nical la b orat or y, E C G, B P, a n d heart rate
a b n or malities of p ote ntial cli nical c o ncer n will be descri be d. Safet y data will be prese nte d i n 
ta b ular a n d/ or gra p hical f or mat a n d s u m marize d descri pti vel y, w here a p pr o priate.
Me dical hist or y  a n d P E i nf or mati o n, as a p plica ble, c ollecte d d uri n g t he c o urse of t he st u d y, 
will be c o nsi dere d s o urce data a n d will n ot be re q uire d t o be re p orte d, u nless ot her wise 
n ote d. H o we ver, a n y u nt o war d fi n di n g s i de ntifie d o n p h ysical c o n d ucte d d uri n g t he acti ve 
c ollecti o n peri o d will be ca pt ure d as A Es, if t h ose fi n di n gs meet t he defi niti o n of a n A E. 
Data c ollecte d at scree ni n g t hat are use d f or i ncl usi o n/e xcl usi o n criteria, s uc h as la b orat or y  
data, E C Gs, a n d v ital si g ns, will be c o nsi dere d s o urce data, a n d will n ot be re q uire d t o be 
re p orte d, u nless ot her wise n ote d. De m o gra p hic data c ollecte d at scree ni n g will be re p orte d.
T he n u m ber ( %) of partici pa nts wit h ma xi m u m p ost d ose Q Tc F val ues a n d ma xi m u m 
i ncreases fro m baseli ne i n t he f oll o wi n g cate g ories will be ta b ulate d b y  treat me nt: 
S afet y Q Tc F Assess me nt
De gree of Pr ol o n g ati o n
Mil d ( ms)
M o der ate ( ms)
Se vere ( m s)
A bs ol ute val ue
> 4 5 0 ‑ 4 8 0
> 4 8 0 ‑ 5 0 0
> 5 0 0
I ncrease fr o m baseli ne
3 0 ‑ 6 0
> 6 0
9. 3. 5. E x pl or at or y E n d p oi nt s A n al ysis
Details o n t he a nal ys es of E x pl orat or y e n d p oi nts will be descri be d i n t he S A P.
9. 4. I nteri m A n al yses
N o i nteri m a nal ys is will be c o n d ucte d f or t his st u d y. As t his is a s p o ns or -o pe n st u d y , t he 
s p o ns or ma y c o n d uct u n bli n de d re vie ws of t he data d uri n g t he c o urse of t he st u d y f or t he 
p ur p ose of safet y assess me nt, facilitati n g P K/ P D m o deli n g, a n d/ or s u p p orti n g cli nical 
de vel o p me nt. 
9. 5. S a m ple Size Deter mi n ati o n
A sa m ple size of 4 2 ( 7 per se q ue nce) partici pa nts will pr o vi de a p pr o xi matel y 9 9 % p o wer t o 
detect a 5 msec differe nce bet wee n m o xifl o xaci n a n d place b o at hist orical m o xifl o xaci n
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 1
T ma x ( 3 h o ur) t o de m o nstrate t he st u d y se nsiti vit y , if t he e x pecte d mea n differe nce bet wee n 
m o xifl o xaci n a n d place b o is n o less t ha n 1 0 msec at T ma x. 
T his calc ulati o n use d a 1 -side d 5 % paire d t -test a n d ass u me d a c o nser vati ve esti mate of 
c o m m o n i ntra-s u bject sta n dar d de viati o n of 5. 61 msec f or t he c ha n ge fr o m baseli ne i n Q Tc F, 
base d o n a pre vi o us st u d y  ( C 5 2 4 1 0 0 1). Pre vi o us P C R U T Q T st u dies ( A 4 3 0 1 0 2 3, A 3 9 2 1 0 2 8, 
A 5 7 6 1 0 1 6, A 5 9 5 1 1 5 1, A 5 2 7 1 0 3 2, A 4 2 5 1 0 2 5, A 7 6 9 1 0 1 7 a n d B 1 8 1 1 0 6 2) h a d an a vera ge 
dr o p o ut rate of a p pr o xi matel y  2 %. Ass u mi n g a 2 % dr o p o ut rate, 4 1 partici pa nt s w o ul d 
pr o vi de a p pr o xi matel y 9 9 % p o wer t o de m o nstrate t he st u d y  se nsiti vit y. 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 2
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N SI D E R A TI O N S
1 0. 1. A p pe n di x 1: Re g ul at or y, Et hic al, a n d St u d y O versi g ht C o nsi der ati o ns
1 0. 1. 1. Re g ul at or y a n d Et hic al C o nsi der ati o ns
T his st u d y  will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g:

C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes, i ncl u di n g t he 
Declarati o n of Helsi n ki a n d CI O M S I nter nati o nal Et hical G ui deli nes ;

A p plica ble I C H G C P g ui deli nes ;

A p plica ble la ws a n d re g ulati o ns , i ncl u di n g a p plica ble pri vac y la ws.
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C D, S R S D(s) , a n d ot her rele va nt d oc u me nts 
(e g, a d vertise me nts) m ust be re vie we d a n d a p pr o ve d b y  t he s p o ns or, s u b mitte d t o a n IR B/ E C 
b y  t he i n vesti gat or, a n d re vie we d a n d a p pr o ve d b y  t he I R B/ E C bef ore t he st u d y is i nitiate d.
A n y  a me n d me nts t o t he pr ot oc ol will re q uire IR B/ E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma de t o t he st u d y desi g n, e xce pt f or c ha n ges necessar y  t o eli mi nate a n i m me diate 
hazar d t o st u d y  partici pa nts.
Pr ot oc ols a n d a n y s u bsta ntial a me n d me nts t o t he pr ot oc ol will re q uire healt h a ut h orit y  
a p pr o val p ri or t o i nitiati o n e xce pt f or c ha n ges necessar y t o eli mi nate a n i m me diate hazar d t o 
st u d y partici pa nts.
T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:

Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y  t o t he I R B/ E C a n n uall y or 
m ore fre q ue ntl y i n acc or da nce wit h t he re q uire me nts, p olicies, a n d pr oce d ures 
esta blis he d b y t he I R B/ E C;

N otif y i n g t he I R B/ E C of S A Es or ot her si g nifica nt safety fi n di n gs as re q uire d b y 
I RB/ E C pr oce d ures ;

Pr o vi di n g o versi g ht of t he c o n d uct of t he st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C F R, I C H G C P g ui deli nes, t he I R B/ E C, E ur o pea n re g ulati o n 
5 3 6/ 2 0 1 4 f or cli nical st u dies, E ur o pea n Me dical De vice Re g ulati o n 2 0 1 7/ 7 4 5 f or 
cli nical de vice researc h, a n d all ot her a p plica ble l ocal re g ulati o ns .
1 0. 1. 1. 1. Re p orti n g of S afet y Iss ues a n d Seri o us Bre ac hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y a n a p plica ble 
re g ulat or y a ut h ority i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat mig ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of t he st u d y 
i nter ve nti o n, Pfizer s h o ul d be i nf or me d i m me diatel y.  
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 3
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he s t u d y partici pa nt s a gai nst a ny i m me diate hazar d, a n d 
of a n y seri o us breac hes of t his pr ot oc ol or of t he I C H G C P g ui deli nes t hat t he i n vesti gat or 
bec o mes a ware of.
1 0. 1. 2. I nf or me d C o nse nt Pr ocess
T he i n vesti gat or or t he i n vesti gat or’s re prese ntati ve will e x plai n t he nat ure of t he st u d y, 
i ncl u di n g t he ris ks a n d be nefits, t o t he partici pa nt a n d a ns wer all q uesti o ns re gar di n g t he 
st u d y. T he partici pa nt s h o ul d be gi ve n s ufficie nt ti me a n d o p p ort u nit y t o as k q uesti o ns a n d t o 
deci de w het her or n ot t o partici pate i n t he tr ial.
Partici pa nts m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y . Partici pa nts will be 
re q uire d t o si g n a state me nt of i nf or me d c o nse nt t hat meets t he re q uire me nts of 2 1 C F R 5 0, 
l ocal re g ulati o ns, I C H g ui deli nes, pri vac y  a n d data pr otecti o n re q uireme nts, w here 
a p plica ble, a n d t he I R B/ E C or st u d y  ce nter.
T he i n vesti gat or m ust e ns ure t hat eac h partici pa nt is f ull y i nf or me d a b o ut t he nat ure a n d 
o bjecti ves of t he st u d y, t he s hari n g of data relate d t o t he st u d y, a n d p ossi ble ris ks ass ociate d 
wit h partici pati o n, i ncl u di n g t he ris ks ass ociate d wit h t he pr ocessi n g of t he partici pa nt ’s 
pers o nal data. 
T he partici pa nt m ust be i nf or me d t hat t heir pers o nal st u d y -relate d data will be use d b y t he 
s p o ns or i n acc or da nce wit h l ocal data pr otecti o n la w. T he le vel of discl os ure m ust als o be 
e x plai ne d t o t he partici pa nt.
T he partici pa nt m ust be i nf or me d t hat t heir me dical rec or ds ma y  be e xa mi ne d b y Cli nical 
Q ualit y  Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he s p o ns or, b y 
a p pr o priate I RB/ E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities.
T he i n vesti gat or f urt her m ust e ns ure t hat eac h st u d y  partici pa nt is f ull y i nf or me d a b o ut t heir
ri g ht t o access a n d c orrect t heir pers o nal data a n d t o wit h dra w c o nse nt f or t he pr ocessi n g of 
t heir pers o nal data.
T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date o n w hic h t he writte n c o nse nt was 
o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n t he I CD.
Partici pa nts m ust be rec o nse nte d t o t he m ost c urre nt versi o n of t he I R B/ E C-a p pr o ve d I CD (s) 
d uri n g t heir partici pati o n i n t he st u d y as re q uire d per l ocal re g ulati o ns.
A c o p y of t he I C D (s) m ust be pr o vi de d t o t he partici pa nt.
A partici pa nt w h o is rescree ne d is n ot re q uire d t o si g n a n ot her I CD if t he rescree ni n g occ urs 
wit hi n 2 8 da y s fr o m t he pre vi o us IC D si g nat ure date.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 4
1 0. 1. 3. D at a Pr otecti o n
All parties will c o m pl y  wit h all a p plica ble la ws, i ncl u di n g la ws re gar di n g t he i m ple me ntati o n 
of or ga nizati o nal a n d tec h nical meas ures t o e ns ure pr otecti o n of partici pa nt data.
Partici pa nts’ pers o nal data will be st ore d at t he st u d y  site i n e ncr ypte d electr o nic a n d/ or pa per 
f or m a n d will be pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m t o e ns ure t hat o nl y  
a ut h oriz e d st u d y staff ha ve access. T he st u d y site will i m ple me nt a p pr o priate tec h nical a n d 
or ga nizati o nal meas ures t o e ns ure t hat t he pers o nal data ca n be rec o vere d i n t he e ve nt of 
disaster. I n t he e ve nt of a p ote ntial pers o nal data breac h, t he st u d y site will be res p o nsi ble f or 
deter mi ni n g w het her a pers o nal data breac h has i n fact occ urre d a n d, if s o, pr o vi di n g breac h 
n otificati o ns as re q uire d b y  la w.
T o pr otect t he ri g hts a n d free d o ms of partici pa nts wit h re gar d t o t he pr ocessi n g of pers o nal 
data, partici pa nts will be assi g ne d a si n gle, partici pa nt -s pecific n u merical c o de. A n y 
partici pa nt rec or ds or data sets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he n u merical 
c o de; partici pa nt na mes will n ot be tra nsferre d. All ot her i de ntifia ble data tra nsferre d t o t he 
s p o ns or will be i de ntifie d b y t his si n gle, partici pa nt -s pecific c o de. T he st u d y site will 
mai ntai n a c o nfi de ntial list of partici pa nt s w h o partici pate d i n t he st u d y, li n ki n g eac h 
partici pa nt ’s n u merical c o de t o t heir act ual i de ntit y a n d me dical rec or d I D. I n case of data 
tra nsfer, t he s p o ns or will pr otect t he c o nfi de ntialit y of partici pa nts’ pers o nal data c o nsiste nt 
wit h t he cli nical st u d y agree me nt a n d a p plica ble pri vac y  la ws.
I nf or mati o n tec h n ol o g y s yste ms use d t o c ollect, pr ocess, a n d st ore st u d y-relate d data are 
sec ure d by t ec h nical a n d or ga nizati o nal sec urit y m eas ures desi g ne d t o pr otect s uc h data 
a gai nst acci de ntal or u nla wf ul l oss, alterati o n, or u na ut h orize d discl os ure or access.
T he s p o ns or mai ntai ns sta n dar d o perati n g pr oce d ures o n h o w t o res p o n d i n t he e ve nt of 
u na ut h orize d access, use, or discl os ure of s p o ns or i nf or mati o n or s y ste ms.
1 0. 1. 4. C o m mittees Str uct ure
1 0. 1. 4. 1. D at a M o nit ori n g C o m mittee 
T his st u d y  will n ot use an E- D M C.
1 0. 1. 5. Disse mi n ati o n of C li nic al St u d y D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y res ults t hr o u g h p osti n g t he 
res ults of st u dies o n w w w.cli nicaltrials . g o v ( Cli nical Trials. g o v), t he E u dra C T/ C TIS , a n d/ or 
w w w. pfizer .c o m, a n d ot her p u blic re gistries a n d we bsites i n acc or da nce wit h a p plica ble l ocal 
la ws/re g ulati o ns. I n a d diti o n, Pfizer re p orts st u d y res ults o utsi de of t he re q uire me nts of l ocal 
la ws/re g ulati o ns p urs ua nt t o its S O Ps.
I n all cases, st u dy res ults are re p orte d b y Pfizer i n a n o bjecti ve, acc urate, bala nce d, a n d 
c o m plete ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u d y or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 5
w w w.cli nicaltrials . g o v
Pfizer p osts cli nical trial res ults o n w w w.cli nicaltrials. g o v f or Pfizer- s p o ns ore d i nter venti o nal 
st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safet y a n d/ or efficac y of a pr o d uct, 
re gar dless of t he ge o gra p hical l ocati o n i n w hic h t he st u d y is c o n d ucte d. T hese r es ults are 
s u b mitte d f or p osti n g i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y U S la w.
E u dra C T / C TIS
Pfizer p osts cli nical trial res ults o n E u dra C T / C TIS f or Pfizer-s p o ns ore d i nter ve nti o nal st u dies 
i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y E U re q uire me nts.
w w w. pfizer .c o m
Pfizer p osts C S R s y n o pses a n d plai n -la n g ua ge st u d y res ults s u m maries o n w w w. pfizer .c o m 
f or Pfizer-s p o ns ore d i nter ve nti o nal st u dies at t he sa me ti me t he c orres p o n di n g st u d y res ults 
are p oste d t o w w w.cli nicaltrials . g o v. C S R s y n o pses will ha ve pers o nall y  i de ntifia ble 
i nf or mati o n a n o ny m ize d.
D oc u me nts wit hi n mar keti n g a p plicati o ns
Pfizer c o m plies wit h a p plica ble l ocal la ws/re g ulati o ns t o p u blis h cli nical d oc u me nts i ncl u de d 
i n mar keti n g a p plicati o ns. Cli nical d oc u me nts i ncl u de s u m mar y d oc u me nts a n d C S Rs 
i ncl u di n g t he pr ot oc ol a n d pr ot oc ol a me n dme nts, sa m ple C R Fs, a n d S A P s. Cli nical 
d oc u me nts will ha ve pers o nall y  i de ntifia ble i nf or mati o n a n o n ymize d.
Data shari n g
Pfizer pr o vi des researc hers sec ure access t o partici pa nt -le vel data or f ull C S Rs f or t he 
p ur p oses of “ b o na -fi de scie ntific researc h” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of 
t he disease, tar get, or c o m p o u n d class. Pfizer will ma ke data fr o m t hese trials a vaila ble 
1 8 m o nt hs after st u d y  c o m pleti o n. Partici pa nt -le vel data will be a n o ny m ize d i n acc or da nce 
wit h a p plica ble pri vac y  la ws a n d re g ulati o ns. C S Rs will ha ve pers o nally i de ntifia ble 
i nf or mati o n a n o n y m ize d.
Data re q uests are c o nsi dere d fr o m q ualifie d researc hers wit h t he a p pr o priate c o m pete ncies t o 
perf or m t he pr o p ose d a nal y ses. Researc h tea ms m ust i ncl u de a bi ostatisticia n. Data will n ot 
be pr o vi de d t o a p plica nts wit h si g nifica nt c o nflicts of i nterest, i ncl u di n g i n di vi d uals 
re q uesti n g access f or c o m mercial/c o m petiti ve or le gal p ur p oses.
1 0. 1. 6. D at a Q u alit y Ass ur a nce
All partici pa nt data relati n g t o t he st u d y will be rec or de d o n pri n te d or electr o nic C R F u nless 
tra ns mitte d t o t he s p o ns or or desi g nee electr o nicall y (e g, la b orat or y data). T he i n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 6
G ui da nce o n c o m pleti o n of C R Fs will be pr o vi de d i n t he C R F C o m pleti o n Re q uire me nts 
d oc u me nt.
T he i n vesti gat or m ust e ns ure t hat t he C R Fs are sec urel y st ore d at t he st u d y site i n e ncr y pte d 
electr o nic a n d/ or pa per f or m a n d are pass w or d -pr otecte d or sec ure d i n a l oc ke d r o o m t o 
pre ve nt access b y u na ut h orize d t hir d parties.
T he i n vesti gat or m ust per mit st u d y -relate d m o nit ori n g, a u dits, I R B/ E C re vie w, a n d 
re g ulat or y a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce rec or ds a n d d oc u me nts.
T his verificati o n ma y  als o occ ur after st u dy c o m pleti o n. I t is i m p orta nt t hat t he 
i n vesti gat or(s) a n d t heir rele va nt pers o n nel are a vaila ble d uri n g t he m o nit ori n g visits a n d 
p ossi ble a u dits or i ns pecti o ns a n d t hat s ufficie nt ti me is de v ote d t o t he pr ocess.
M o nit ori n g details descri bi n g strate g y, i ncl u di n g defi niti o n of st u d y-critical data ite ms a n d 
pr ocesses (e g, ris k-base d i nitiati ves i n o perati o ns a n d q ualit y , s uc h as ris k m a na ge me nt a n d 
m iti gati o n strate gies a n d anal yt ical ris k- base d m o nit ori n g), met h o ds, res p o nsi bilities , a n d 
re q uireme nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d m o nit ori n g tec h ni q ues 
(ce ntral, virt ual , or o n-site m o nit ori n g), are pr o vi de d i n t he data ma na ge me nt pla n a n d 
m o nit ori n g pla n mai ntai ne d a n d utilize d b y  t he s p o ns or or desi g nee.
T he s p o ns or or desi g nee is res p o nsi ble f or t he data ma na ge me nt of t his st u d y, i ncl u di n g 
q ualit y  c hec ki n g of t he data.
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C D s, pertai ni n g t o t he c o n d uct of t his st u d y m ust 
be retai ne d b y t he i n vesti gat or f or 1 5 ye ars after st u d y c o m pleti o n u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y be destr o ye d d uri n g 
t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he s p o ns or. N o rec or ds ma y  be 
tra nsferre d t o a n ot her l ocati o n or party wit h o ut writt e n n otificati o n t o t he s p o ns or. T he 
i n vesti gat or m ust e ns ure t hat t he rec or ds c o nti n ue t o be st ore d sec urely f or as l o n g as t he y are 
mai ntai ne d.
W he n partici pa nt data are t o be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h 
data are pr o m ptl y a n d irre v oca bl y delete d fr o m all s yste ms.
T he i n vesti gat or(s) will n otif y  t he s p o ns or or its a ge nts i m me diatel y of a n y re g ulat or y 
i ns pecti o n n otificati o n i n relati o n t o t he st u d y. F urt her m ore, t he i n vesti gat or will c o o perate 
wit h t he s p o ns or or its a ge nts t o pre pare t he i n vesti gat or site f or t he i ns pecti o n a n d will all o w 
t he s p o ns or or its a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n. T he 
i n vesti gat or site a n d i n vesti gat or will pr o m ptl y res ol ve a n y discre pa ncies t hat are i de ntifie d 
bet wee n t he st u d y data a n d t he partici pa nt’s me dical rec or ds. T he i n vesti gat or will pr o m ptl y 
pr o vi de c o pies of t he i ns pecti o n fi n di n gs t o t he s p o ns or or its a ge nt. Bef ore res p o nse 
s u b missi o n t o t he re g ulat or y a ut h orities, t he i n vesti gat or will pr o vi de t he s p o ns or or its 
a ge nts wit h a n o p p ort u nit y t o re vie w a n d c o m me nt o n res p o nses t o a n y s uc h fi n di n gs.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 7
1 0. 1. 7. S o urce D oc u me nts
S o urce d oc u me nts pr o vi de e vi de nce f or t he e xiste nce of t he partici pa nt a n d s u bsta ntiate t he 
i nte grity of t he data c ollecte d. S o urce d oc u me nts are file d at t he i n vesti gat or site.
Data re p orte d o n t he C R F or e ntere d i n t he e C R F t hat are fr o m s o urce d oc u me nts m ust be 
c o nsiste nt wit h t he s o urce d oc u me nts or t he discre pa ncies m ust be e x plai ne d . T he 
i n vesti gat or ma y nee d t o re q uest pre vi o us me dical rec or ds or tra nsfer rec or ds, de pe n di n g o n 
t he st u d y. Als o, c urre nt me dical rec or ds m ust be a vaila ble.
I n t his st u dy, t he C R F will ser ve as t he s o urce d oc u me nt. A d oc u me nt m ust be a vaila ble at 
t he i n vesti gati ve site t hat i de ntifies t h ose data t hat will be rec or de d o n t he C R F a n d f or w hic h 
t he C R F will be t he s o urce d oc u me nt.
Defi niti o n of w hat c o nstit utes a s o urce d oc u me nt a n d its ori gi n ca n be f o u n d i n t he S o urce 
D oc u me nt L ocat or , w hic h is mai ntai ne d b y t he s p o ns or’s desi g nee ( Pfizer C R U).
Descri pti o n of t he use of t he c o m p uterize d s yste m is d oc u me nte d i n t he Data Ma na ge me nt 
Pla n , w hic h is mai ntai ne d b y t he s p o ns or’s desi g nee ( Pfizer C R U).
T he i n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce rec or d) t hat s u p p orts t he 
i nf or mati o n e ntere d i n t he CR F.
T he s p o ns or or desi g nee will perf or m m o nit ori n g t o c o nfir m t hat data e ntere d i nt o t he C R F 
b y  a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce d oc u me nts; 
t hat t he safety a n d ri g hts of partici pa nts are bei n g pr otecte d; a n d t ha t t he st u d y is bei n g 
c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y  
a gree me nts, IC H G C P g ui deli nes, a n d all a p plica ble re g ulat or y  re q uire me nts.
1 0. 1. 8. Use of Me dic al Rec or ds
T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are re q ueste d b y 
Pfizer Safet y , w here et hicall y a n d scie ntificall y j ustifie d a n d per mitte d b y l ocal re g ulati o ns, 
t o e ns ure partici pa nt safet y.
D ue t o t he p ote ntial f or a partici pa nt t o be re -i de ntifie d fr o m t heir me dical rec or ds, t he 
f ollo wi n g acti o ns m ust be ta ke n w he n me dical rec or ds are se nt t o t he s p o ns or or s p o ns or 
desi g nee:

T he i n vesti gat or or site staff m ust re dact pers o nal i nf or mati o n fr o m t he me dical 
rec or d. T he pers o nal i nf or mati o n i ncl u des, b ut is n ot li mite d t o, t he f oll o wi n g:  
partici pa nt na mes or i nitials , partici pa nt dates (e g, birt h date, date of h os pital 
a d missi o n/ disc har ge, date of deat h), partici pa nt i de ntificati o n n u m bers (e g, S ocial 
Sec urit y  n u m ber, healt h i ns ura nce n u m ber, me dical rec or d n u m ber, 
h os pital/i nstit uti o n i de ntifier), p artici pa nt l ocati o n i nf or mati o n (e g, street a d dress, 
cit y, c o u ntr y, p ostal c o de, IP a d dress), partici pa nt c o ntact i nf or mati o n (e g, 
tele p h o ne/fa x n u m ber, e mail a d dress).
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 8

Eac h me dical rec or d m ust be tra ns mitte d t o t he s p o ns or or s p o ns or desi g nee usi n g 
s yste ms wit h tec h nical a n d or ga nizati o nal sec urit y meas ures t o e ns ure t he pr otecti o n 
of pers o nal data (e g, Fl ore nce is t he preferre d s ys te m if a vaila ble). 
T here ma y  be u n pla n ne d sit uati o ns w here t he s p o ns or ma y re q uest me dical rec or ds (e g, 
s hari n g me dical rec or ds s o t hat t he s p o ns or ca n pr o vi de st u d y-relate d a d vice t o t he 
i n vesti gat or). T he me dical rec or ds s h o ul d be s u b mitte d acc or di n g t o t he pr oce d ure descri be d 
a b o ve.
1 0. 1. 9. St u d y a n d Site St art a n d Cl os ure
T he st u d y  start date is t he date of t he first partici pa nt’s first visit.
T he s p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y  site or ter mi nate t he st u d y at a n y 
ti me f or a ny reas o n at t he s ole discreti o n of t he s p o ns or , i ncl u di n g ( b ut n ot li mite d t o) 
re g ulat or y a ut h ority decisi o n, c ha n ge i n o pi ni o n of t he I R B/ E C, or c ha n ge i n be nefit -ris k 
assess me nt . St u d y  sites will be cl ose d u p o n st u d y c o m pleti o n. A st u d y site is c o nsi dere d 
cl ose d w he n all re q uire d d oc u me nts a n d st u d y  s u p plies ha ve bee n c ollecte d a n d a st u d y-site 
cl os ure visit has bee n perf or me d.
T he i n vesti gat or ma y  i nitiate st u d y-site cl os ure at a n y ti me u p o n n otificati o n t o t he s p o ns or 
or desi g nee ( Pfizer C R U) if re q ueste d t o d o s o by t he res p o nsi ble I R B/ E C or if s uc h 
ter mi nati o n is re q uire d t o pr otect t he healt h of st u d y partici pa nts.
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he s p o ns or ma y i ncl u de b ut are n ot li mite d 
t o:

Fail ure of t he i n vesti gat or t o c o m pl y  wit h t he pr ot oc ol, t he re q uire me nts of t he 
I RB/ E C or l ocal healt h a ut h orities, t he s p o ns or ’s pr oce d ures, or t he I CH G C P 
g ui deli nes ;

I na de q uate recr uit me nt of partici pa nts b y  t he i n vesti gat or;

Disc o nti n uati o n of f urt her st u d y  i nter ve nti o n de vel o p me nt.
If t he st u dy is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
in vesti gat ors, t he E C s/I R Bs, t he re g ulat or y a ut h orities, a n d a n y C R O (s) use d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uire me nts. T he in vesti gat or s hall pr o m ptl y  i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f oll o w- u p.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a ny c o nflict 
bet wee n t he c o ntract a n d t his pr ot oc ol, t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts.
1 0. 1. 1 0. P u blic ati o n P olic y
F or m ultice nter trials, t he pri mar y  p u blicati o n will be a j oi nt p u blicati o n de vel o pe d by t he 
i n vesti gat or a n d Pfizer re p orti n g t he pri mar y e n d p oi nt(s) of t he st u d y c o veri n g all st u d y sites. 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7 9
T he i n vesti gat or a grees t o refer t o t he pri mar y  p u blicati o n i n a n y s u bse q ue nt p u blicati o ns. 
Pfizer will n ot pr o vi de a n y fi na ncial c o m pe nsati o n f or t he i n vesti gat or’s partici pati o n i n t he 
pre pa rati o n of t he pri mar y c o n gress a bstract, p oster, prese ntati o n, or pri mar y ma n uscri pt f or 
t he st u d y.
I n vesti gat ors are free t o p u blis h i n di vi d ual ce nter res ults t hat t he y dee m t o be cli nicall y 
mea ni n gf ul after p u blicati o n of t he o verall res ults of t he st u d y or 1 2 m o nt hs after pri mar y  
c o m pleti o n date or st u d y c o m pleti o n at all sites, w hic he ver occ urs first, s u bject t o t he ot her 
re q uire me nts descri be d i n t his secti o n.
T he i n vesti gat or will pr o vi de Pfizer a n o p p ort u nit y  t o re vie w a n y pr o p ose d p u blicati o n or 
a n y ot her t y pe of discl os ure of t he st u d y res ults (c ollecti vel y, “ p u blicati o n”) bef ore it is 
s u b mitte d or ot her wise discl ose d a n d will s u b mit all p u blicati o ns t o Pfizer 3 0 da y s bef ore 
s u b missi o n. If a ny pate nt acti o n is re q uire d t o pr otect i ntellect ual pr o pert y ri g hts, t he 
i n vesti gat or a grees t o dela y t he discl os ure f or a peri o d n ot t o e xcee d a n a d diti o nal 6 0 da ys 
u p o n re q uest fr o m Pfizer. T his all o ws Pfizer t o pr otect pr o prietar y  i nf or mati o n a n d t o pr o vi de 
c o m me nts, a n d t he i n vesti gat or will, o n re q uest , re m o ve a ny pre vi o usl y u n discl ose d 
c o nfi de ntial i nf or mati o n bef ore discl os ure, e xce pt f or a n y st u d y- i nter ve nti o n or  
Pfizer -relate d i nf or mati o n necessar y f or t he a p pr o priate scie ntific prese ntati o n or 
u n dersta n di n g of t he st u d y  res ults.  F or j oi nt p u blicati o ns, s h o ul d t here be disa gree me nt 
re gar di n g i nter pretati o n a n d/ or prese ntati o n of s pecific a nalys is res ults, res ol uti o n of, a n d 
res p o nsi bilit y f or, s uc h disa gree me nts will be t he c ollecti ve res p o nsi bilit y of all a ut h ors of 
t he p u blicati o n.
F or all p u blic ati o ns relati n g t o t he st u d y, t he i n vesti gat or a n d Pfizer will c o m pl y wit h 
rec o g nize d et hical sta n dar ds c o ncer ni n g p u blicati o ns a n d a ut h ors hi p, i ncl u di n g t h ose 
esta blis he d b y t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors. T he i n vesti gat or will 
dis cl ose a n y relati o ns hi p wit h Pfizer a n d a n y rele va nt p ote ntial c o nflicts of i nterest, i ncl u di n g 
a n y fi na ncial or pers o nal relati o ns hi p wit h Pfizer, i n a n y p u blicati o ns. All a ut h ors will ha ve 
access t o t he rele va nt statistical ta bles, fi g ures, a n d re p orts (i n t heir ori gi nal f or mat) re q uire d 
t o de vel o p t he p u blicati o n.
1 0. 1. 1 1. S p o ns or’s Me dic all y Q u alifie d I n di vi d u al
T he c o ntact i nf or mati o n f or t he s p o ns or ’s M QI
f or t he st u d y is d oc u me nte d i n t he st u d y 
c o ntact list l ocate d i n t he C T M S . 
T o facilitate access t o t heir in vesti gat or a n d t he s p o ns or ’s M QI f or st u d y-relate d me dical 
q uesti o ns or pr o ble ms fr o m n o nst u d y healt hcare pr ofessi o nals, partici pa nts are pr o vi de d wit h 
a n E C C at t he ti me of i nf or me d c o nse nt. T he E C C c o ntai ns, at a mi ni m u m, (a) pr ot oc ol a n d 
st u d y i nter ve nti o n i de ntifiers, ( b) partici pa nt’s st u d y i de ntificati o n n u m ber, a n d (c) site 
e mer ge nc y p h o ne n u m ber acti ve 2 4 h o urs/ da y, 7 da ys per wee k.
T he E C C is i nte n de d t o a u g me nt, n ot re place, t he esta blis he d c o m m u nicati o n pat h wa y s 
bet wee n t he partici pa nt a n d t heir i n vesti gat or a n d site staff, a n d bet wee n t he i n vesti gat or a n d 
s p o ns or st u d y tea m. T he E C C is o nl y t o be use d b y healt hcare pr ofessi o nals n ot i n v ol ve d i n 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 0
t he researc h st u dy, as a mea ns of reac hi n g t he i n vesti gat or or site staff relate d t o t he care of a 
partici pa nt.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 1
1 0. 2. A p pe n di x 2: Cli nic al L a b or at or y Tests
T he f oll o wi n g safet y la b orat or y  tests will be perf or me d at ti mes defi ne d i n t he S o A secti o n of 
t his pr ot oc ol. A d diti o nal la b orat or y res ults may be re p orte d o n t hese sa m ples as a res ult of 
t he met h o d of a nalys is or t he t ype of a nal yz er use d b y t he cli nical la b orat or y, or as deri ve d 
fr o m calc ulate d val ues. T hese a d diti o nal tests w o ul d n ot re q uire a d diti o nal c ollecti o n of 
bl o o d. U nsc he d ule d cli nica l la b orat or y meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he 
st u d y t o assess a ny percei ve d safet y iss ues.
T a ble 4 .
Pr ot oc ol -Re q uire d S afet y L a b or at or y Assess me nts
H e m at ol o g y
C he mistr y
Uri n al ysis
Ot her
H e m o gl o bi n
H e m at ocrit
R B C c o u nt
Platelet c o u nt
W B C c o u nt
T otal ne utr o p hils ( A bs)
E osi n o p hils ( A bs)
M o n oc ytes ( A bs)
Bas o p hils ( A bs)
L y m p h oc ytes ( A bs)
Urea a n d creati ni ne
C ystati n C a n d eG F R
Gl uc ose (fasti n g)
Calci u m
S o di u m
P otassi u m
C hl ori de
T otal C O 2 ( bicar b o nate)
A S T, A L T
G G T
T otal bilir u bi n
Al kali ne p h os p hatase
Uric aci d
Al b u mi n
T otal pr otei n
L ocal di pstic k:
p H
Gl uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nitrites
Le u k oc yte esterase
La b orat or y:
Micr osc o p y a n d 
cult ure a

Pre g na nc y test ( β -h C G) d

Uri ne dr u g scree ni n g c

C o vi d -1 9 testi n g
At scree ni n g:

F S H b

He patitis B s urface 
a nti ge n

He patitis B s urface 
a nti b o d y e

He patitis B c ore a nti b o d y

He patitis C a nti b o d y

HI V
a.
O nl y if U T I is s us pecte d a n d uri ne di pstic k is p ositi ve f or nitrites or le u k oc yte esterase or b ot h.
b.
F or c o nfir mati o n of p ost me n o pa usal stat us o nl y.
c.
T he mi ni m u m re q uire me nt f or dr u g scree ni n g i ncl u des c oca ine, T H C, o piates/ o pi oi ds, be nz o diaze pi nes, 
a n d a m p heta mi nes ( ot her s are site a n d st u d y s pecific).
d.
L ocal uri ne testi n g will be sta n dar d f or t he pr ot oc ol u nless ser u m tes ti n g is re q uire d b y l ocal re g ulati o n 
or I R B/ E C. Ser u m or uri ne -h C G f or fe male partici pa nts of c hil d beari n g p ote ntial.
e.
H Bs A b will be teste d if H Bs A g a n d/ or H Bc A b is p ositi ve.
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a ny 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he C R F.
La b orat or y  res ults t hat c o ul d u n bli n d t he st u d y a n d ha ve bee n c ollecte d f or t he p ur p ose of t he 
st u d y will n ot be re p orte d t o i n vesti gat or sites or ot her bli n de d pers o n nel u ntil t he st u d y  has 
bee n u n bli n de d.
A n y  re mai ni n g ser u m/ plas ma fr o m sa m ples c ollecte d f or cli nical safety la b orat or y 
meas ure me nts at baseli ne a n d at all ti mes after d ose a d mi nistrati o n ma y  be retai ne d a n d 
st ore d f or t he d urati on of t he st u d y . U p o n c o m pleti o n of t he st u d y, t hese retai ne d safet y 
sa m ples ma y be use d f or t he assess me nt of e x pl orat or y safety bi o mar kers or u ne x pecte d 
safety fi n di n gs. T hese data will n ot be i ncl u de d i n t he C S R. Sa m ples t o be use d f or t his 
p ur p ose will be s hi p pe d t o eit her a Pfizer -a p pr o ve d B B S facilit y or ot her desi g nate d 
la b orat or y a n d retai ne d f or u p t o 1 ye ar f oll o wi n g t he c o m pleti o n of t he st u d y .
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 2
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E v al u ati n g, F oll o w - Up, a n d Re p orti n g
1 0. 3. 1. Defi niti o n of A E
A E Defi niti o n

A n A E is a n y u nt o war d me dical occ urre nce i n a patie nt or cli nical st u d y 
partici pa nt, te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n, w het her or 
n ot c o nsi dere d relate d t o t he st u d y  i nter ve nti o n.

N ote : A n A E ca n t heref ore be a ny u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n 
a b n or mal la b orat or y fi n di n g), sy m pt o m, or disease ( ne w or e xacer bate d) 
te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n.
E ve nts Meeti n g
t he A E Defi niti o n

A n y  a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or 
uri nal y sis) or ot her safet y assess me nts (e g, E C G, ra di ol o gical sca ns, vital si g n 
meas ure me nts), i ncl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli nicall y  
si g nifica nt i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or. A n y 
a b n or mal test res ults t hat meet a n y of t he c o n diti o ns bel o w m ust be rec or de d as 
a n A E:

Is ass ociate d wit h acc o m pa n yi n g sy m pt o ms ;

Re q uires a d diti o nal dia g n ostic testi n g or me dical/s ur gical i nter ve nti o n ;

Lea ds t o a c ha n ge i n st u d y  dosi n g ( o utsi de of a n y  pr ot oc ol-s pecifie d d ose 
a dj ust me nts) or disc o nti n uati o n fr o m t he st u d y , si g nifica nt a d diti o nal 
c o nc o mita nt dr u g treat me nt, or ot her t hera p y.

E xacer bati o n of a c hr o nic or i nter mitte nt pree xisti n g c o n diti o n, i ncl u di n g a n 
i ncrease i n either fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n.

Ne w c o n diti o n detecte d or dia g n ose d after st u d y i nter ve nti o n a d mi nistrati o n ,
e ve n t h o u g h it ma y ha ve bee n prese nt bef ore t he start of t he st u d y.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y  
i nter ve nti o n or a c o nc o mita nt me dicati o n. O ver d ose per se will n ot be re p orte d as 
a n A E or S A E u nless it is a n i nte nti o nal o ver d ose ta ke n wit h p ossi ble 
s uici dal/self- har mi n g i nte nt. S uc h o ver d oses s h o ul d be re p orte d re gar dless of 
se q uelae.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 3
E ve nts N O T Meeti n g t he A E Defi niti o n

A n y  cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal safety 
assess me nts t hat are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y  t he 
i n vesti gat or t o be m ore se vere t ha n e x pecte d f or t he partici pa nt’s c o n diti o n.

T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms 
of t he disease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he 
partici pa nt’s c o n diti o n.

Me dical or s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y): t he c o n diti o n t hat 
lea ds t o t he pr oce d ure is t he A E.

Sit uati o ns i n w hic h a n u nt o war d me dical occ urre nce di d n ot occ ur (s oci al a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).

A ntici pate d da y -t o-d a y  fl uct uati o ns of pree xisti n g disease(s) or c o n diti o n(s) 
prese nt or detecte d at t he start of t he st u d y  t hat d o n ot w orse n.
1 0. 3. 2. Defi niti o n of a n S A E
A n S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose , meets o ne 
or m ore of t he criteri a liste d bel o w:
a.
Res ults i n de at h
b.
Is life-t hre ate ni n g
T he ter m “life-t hreate ni n g” i n t he defi niti o n of “seri o us” refers t o a n e ve nt i n w hic h 
t he partici pa nt was at ris k of deat h at t he ti me of t he e ve nt. It d oes n ot refer t o a n 
e ve nt t hat h y p ot heticall y mi g ht ha ve ca use d deat h if it were m ore se vere.
c.
Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h o s pit aliz ati o n
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n a d mitte d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or 
o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h y sicia n’s 
office or o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A Es. 
If a c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, t he 
e ve nt is seri o us. W he n i n d o u bt as t o w het her “ h os pitalizati o n” occ urre d or was 
necessar y , t he A E s h o ul d be c o nsi dere d seri o us.
H os pitalizati o n f or electi ve treat me nt of a pree xisti n g c o n diti o n t hat di d n ot w orse n 
fr o m baseli ne is n ot c o nsi dere d a n A E.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 4
A n S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose , meets o ne 
or m ore of t he criteri a liste d bel o w:
d.
Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y

T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y  t o c o n d uct 
n or mal life f u ncti o ns.

T hi s defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vely mi n or me dical 
si g nifica nce, s uc h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, 
i nfl ue nza, a n d acci de ntal tra u ma (e g, s prai ne d a n kle), t hat m a y  i nterfere wit h or 
pre ve nt e ver y d a y  life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n.
e.
Is a c o n ge nit al a n o m al y/ birt h defect
f.
Is a s us pecte d tr a ns missi o n vi a a Pfizer pr o d uct of a n i nfecti o us a ge nt, 
p at h o ge nic or n o n -p at h o ge nic 
T he e ve nt ma y  be s us pecte d fr o m cli nical sy m pt o ms or la b orat or y fi n di n gs 
i n dicati n g a n i nfecti o n i n a partici pa nt e x p ose d t o a Pfizer pr o d uct. T he ter ms 
“s us pecte d tra ns missi o n” a n d “tra ns missi o n” are c o nsi dere d s y n o n y m o us. T hese 
cases are c o nsi dere d u ne x pecte d a n d ha n dle d as seri o us e x pe dite d cases b y 
p har m ac o vi gila nce pers o n nel. S uc h cases are als o c o nsi dere d f or re p orti n g as 
pr o d uct defects, if a p pr o priate.
g.
Ot her sit u ati o ns:

Me dical or scie ntific j u d g me nt s h o ul d be e xercise d b y  t he i n vesti gat or i n deci di n g 
w het her S A E re p orti n g is a p pr o priate i n ot her sit uati o ns, s uc h as si g nifica nt 
me dical e ve nts t hat ma y je o par dize t he partici pa nt or ma y  re q uire me dical or 
s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve 
defi niti o n. T hese e ve nts s h o ul d us uall y  be c o nsi dere d seri o us.

E xa m p les of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve 
treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d 
d y scrasias or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of 
dr u g de pe n de nc y  or dr u g a b use.
1 0. 3. 3. Rec or di n g / Re p orti n g a n d F oll o w - Up of A Es a n d/ or S A E s D uri n g t he Acti ve 
C ollecti o n Peri o d
A E a n d S A E Rec or di n g / Re p orti n g
T he ta ble bel o w s u m marizes t he re q uire me nts f or rec or di n g A Es o n t he C R F a n d f or 
re p orti n g S A Es usi n g t he C T S A E Re p ort F or m t o Pfizer Safet y t hr o u g h o ut t he acti ve 
c ollecti o n peri o d. T hese re q uire me nts are deli neate d f or 3 t ypes of e ve nts: ( 1) S A Es; ( 2) 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 5
A E a n d S A E Rec or di n g / Re p orti n g
n o nseri o us A E s; a n d ( 3) e x p os ure t o t he st u d y i nter ve nti o n u n der st u d y d uri n g 
pre g na nc y  or breastfee di n g, a n d occ u pati o nal e x p os ure. 
It s h o ul d be n ote d t hat t he C T S A E Re p ort F or m f or re p orti n g of S A E i nf or mati o n is n ot 
t he sa me as t he A E pa ge of t he C R F. W he n t he sa me data are c ollecte d, t he f or ms m ust 
be c o m plete d i n a c o nsiste nt ma n ner. A Es s h o ul d be rec or de d usi n g c o ncise me dica l 
ter mi n ol o g y a n d t he sa me A E ter m s h o ul d be use d o n b ot h t he C R F a n d t he C T S A E 
Re p ort F or m f or re p orti n g of S A E i nf or mati o n.
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfizer 
S afet y Wit hi n 2 4 H o urs 
of A w are ness
S A E
All
All
N o nseri o us A E
All
N o ne
E x p os ure t o t he st u d y 
i nter ve nti o n u n der st u d y 
d uri n g pre g na nc y  or 
breastfee di n g
All A E s/ S A Es ass ociate d 
wit h E D P or E D B
N ote: I nsta nces of E D P or 
E D B n ot ass ociate d wit h a n 
A E or S A E are n ot ca pt ure d 
i n t he C R F
All i nsta nces of E D P are 
re p orte d ( w het her or n ot 
t here is a n ass ociate d 
S A E) *
All i nsta nces of E D B are 
re p orte d ( w het her or n ot 
t here is a n ass ociate d 
S A E) * *
E n vir o n me ntal or 
occ u pati o nal e x p os ure 
t o t he pr o d uct u n der 
st u d y t o a 
n o n partici pa nt ( n ot 
i n v ol vi n g E D P or E D B)
N o ne. E x p os ure t o a st u d y 
n o n - partici pa nt is n ot 
c ollecte d o n t he C R F
T he e x p os ure ( w het her or 
n ot t here is a n ass ociate d 
A E or S A E) m ust be 
re p orte d * * *
*
E D P ( wit h or wit h o ut a n ass ociate d S A E): is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort 
F or m a n d E D P S u p ple me ntal F or m.
* * E D B is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m, w hic h w o ul d als o i ncl u de 
details of a n y S A E t hat mi g ht be ass ociate d w it h t he E D B. 
* * * E n vir o n me nt al or o cc u p ati o n al e x p os ure: A E s or S A Es ass ociate d wit h occ u pati o nal e x p os ure 
are re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m. 

W he n a n A E
or S A E occ urs, it is t he res p o nsi bilit y  of t he i n vesti gat or t o re vie w 
all d oc u me ntati o n (e g, h os pital pr o gress n otes, la b orat or y  re p orts, a n d dia g n ostic 
re p orts) relate d t o t he e ve nt.

T he i n vesti gat or will t he n rec or d all rele va nt A E or S A E i nf or mati o n i n t he C R F.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 6
A E a n d S A E Rec or di n g / Re p orti n g

It is n ot acce pta ble f or t he i n vesti gat or t o se n d p h ot oc o pies of t he partici pa nt’s 
me dical rec or ds t o Pfizer Safet y  i n lie u of c o m pleti o n of t he C T S A E Re p ort 
F or m / A E or S A E C R F pa ge.

T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are 
re q ueste d by Pfizer Safet y . I n t his case, all partici pa nt i de ntifiers, wit h t he 
e xce pti o n of t he partici pa nt n u m ber, will be re dacte d o n t he c o pies of t he me dical 
rec or ds bef ore s u b missi o n t o Pfizer Safet y . Refer t o Secti o n 1 0. 1. 8 f or acti o ns 
t hat m ust be ta ke n w he n me dical rec ords are se nt t o t he s p o ns or or s p o ns or 
desi g nee.

T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s ym pt o ms, a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n osis 
( n ot t he i n di vi d ual si g ns/s y m pt o ms) will be d oc u me nte d as t he A E or S A E.
Assess me nt of I nte nsit y
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d 
d uri n g t he st u d y a n d assi g n it t o 1 of t he f oll o wi n g cate g ories: 

Mil d: A t y pe of A E t hat is us uall y  tra nsie nt a n d ma y re q uire o nl y mi ni mal 
treat me nt or t hera pe utic i nter ve nti o n.  T he e ve nt d oes n ot ge nerall y i nterfere wit h 
us ual A D L .

M o derate: A t y pe of A E t hat is us uall y  alle viate d wit h a d diti o nal s pecific 
t hera pe utic i nter ve nti o n. T he e ve nt i nterferes wit h us ual A D L , ca usi n g 
disc o mf ort , b ut p oses n o si g nifica nt or per ma ne nt ris k of har m t o t he researc h 
partici pa nt.

Se vere: A t y pe of A E t hat i nterr u pts us ual A D L , or si g nifica ntl y affects cli nical 
stat us, or ma y re q uire i nte nsi ve t hera pe utic i nter ve nti o n.
A n e ve nt is defi ne d as “seri o us” w he n it meets at least 1 of t he pre defi ne d o utc o mes as 
descri be d i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere.
Assess me nt of C a us alit y

T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y i nter ve nti o n 
a n d eac h occ urre nce of eac h A E or S A E. T he i n vesti gat or will use cli nical 
j u d g me nt t o deter mi ne t he relati o ns hi p.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 7
Assess me nt of C a us alit y

A “reas o na ble p ossi bilit y” of a relati o ns hi p c o n ve ys t hat t here are facts, 
e vi de nce, a n d/ or ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n a 
relati o ns hi p ca n n ot be r ule d o ut.

Alter nati ve ca uses, s uc h as u n derl yi n g disease(s), c o nc o mita nt t hera p y, a n d ot her 
ris k fact ors, as well as t he te m p oral relati o ns hi p of t he e ve nt t o st u d y i nter ve nti o n 
a d mi nistrati o n , will be c o nsi dere d a n d i n vesti gate d.

T he i n vesti gat or will als o c o ns ult t he I B a n d/ or p r o d uct inf or mati o n, f or 
mar kete d pr o d ucts, i n t heir assess me nt.

F or eac h A E or S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes t hat 
t he y have re vie we d t he A E or S A E a n d ha v e pr o vi de d a n assess me nt of ca usalit y .

T here ma y  be sit uati o ns i n w hic h a n S A E has occ urre d a n d t he i n vesti gat or has 
mi ni mal i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o t he s p o ns or. H o we ver, it is 
ver y i m p ort a nt t h at t h e i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y 
f or e ver y e ve nt bef ore t he i niti al tr a ns missi o n of t he S A E d at a t o t he 
s p o ns or.

T he i n vesti gat or ma y  c ha n ge t heir o pi ni o n of ca usalit y  i n li g ht of f oll o w-u p 
i nf or mati o n a n d se n d an S A E f oll o w -u p re p ort wit h t he u p date d ca usalit y  
assess me nt.

T he ca usalit y  assess me nt is o ne of t he criteria use d w he n deter mi ni n g re g ulat or y 
re p orti n g re q uire me nts.

If t he i n vesti gat or d oes n ot k n o w w het her or n ot t he st u d y i nter ve nti o n ca use d t he 
e ve nt, t he n t he e ve nt will be ha n dle d as “relate d t o st u d y i nter ve nti o n” f or 
re p orti n g p ur p oses, as defi ne d b y t he s p o ns or. I n a d diti o n, if t he i n vesti gat or 
deter mi nes t hat a n S A E is ass ociate d wit h st u d y  pr oce d ures, t he i n vesti gat or 
m ust rec or d t his ca usal relati o ns hi p i n t he s o urce d oc u me nts a n d C R F, a n d re p ort 
s uc h a n assess me nt i n t he de dicate d secti o n of t he C T S A E Re p ort F or m a n d i n 
acc or da nce wit h t he S A E re p orti n g re q uire me nts.
F oll o w - Up of A E s a n d S A Es

T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of 
s u p ple me ntal meas ure me nts a n d/ or e val uati o ns, as me dicall y i n dicate d or as 
re q ueste d by t he s p o ns or, t o el uci date t he nat ure a n d/ or ca usality of t he A E or 
S A E as f ull y  as p ossi ble. T his ma y i ncl u de a d diti o nal la b orat or y tests or 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 8
F oll o w - Up of A E s a n d S A Es
i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her 
healt hcare pr o vi ders .

If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d 
f oll o w- u p peri o d, t he i n vesti gat or will pr o vi de Pfizer Safet y wit h a c o p y of a n y 
p ost m orte m fi n di n gs , i ncl udi n g hist o pat h ol o g y .

Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y  s u b mitte d 
d oc u me nts .

T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 2 4 
h o urs of recei pt of t he i nf or mati o n.
1 0. 3. 4. Re p orti n g of S A Es
S A E Re p orti n g t o Pfizer S afet y vi a a n Electr o nic D C T

T he pri mar y  mec ha nis m f or re p orti n g a n S A E t o Pfizer Safet y will be t he 
electr o nic D C T(e g, e S A E or P S S A) .

If t he electr o nic sys te m is u na vaila ble, t he n t he site will use t he pa per S A E re p ort 
f or m (see ne xt secti o n) t o re p ort t he e ve nt wit hi n 2 4 h o urs.

T he site will e nter t he S A E data i nt o t he electr o nic D C T (e g, e S A E or P S S A) or 
pa per f or m (as a p plica ble) as s o o n as t he data bec o me a vaila ble.

After t he st u d y is c o m plete d at a gi ve n site, t he electr o nic D C T will be ta ke n 
off -li ne t o pre ve nt t he e ntr y of ne w data or c ha n ges t o e xisti n g data.

If a site recei ves a re p ort of a ne w S A E fr o m a st u d y partici pa nt or recei ves 
u p date d data o n a pre vi o usl y  re p orte d S A E after t he electr o nic D C T has bee n 
ta ke n off-li ne, t he n t he site ca n re p ort t his i nf or mati o n o n a pa per S A E f or m (see 
ne xt secti o n) or t o Pfizer Safet y  b y tele p h o ne.
S A E Re p orti n g t o Pfizer S afet y vi a t he C T S A E Re p ort F or m

Facsi mile tra ns missi o n of t he C T S A E Re p ort F or m is o ne of t he met h o d s t o 
tra ns mit t his i nf or mati o n t o Pfizer Safet y .

I n circ u msta nces w he n t he facsi mile is n ot w or ki n g, a n alter nati ve met h o d s h o ul d 
be use d, e g, sec ure d ( Tra ns p ort L a yer Sec urit y) or pass w or d-pr otecte d e mail. I f 
n o ne of t hese met h o ds ca n be use d, n otificati o n b y tele p h o ne is acce pta ble wit h a 
c o p y of t he C T S A E Re p ort F or m se nt by o ver ni g ht mail or c o urier ser vice.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 8 9
S A E Re p orti n g t o Pfizer S afet y vi a t he C T S A E Re p ort F or m

I nitial n otificati o n via tele p h o ne d oes n ot re place t he nee d f or t he i n vesti gat or t o 
c o m plete a n d si g n t he C T S A E Re p ort F or m pa ges wit hi n t he desi g nate d 
re p orti n g ti me fra mes.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 0
1 0. 4. A p pe n di x 4: C o ntr ace pti ve a n d B arrier G ui d a nce
1 0. 4. 1. M ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
Male partici pa nts are eli gi ble t o partici pate if t he y  a gree t o t he f oll o wi n g re q uire me nts d uri n g 
t he i nter ve nti o n peri o d a n d f or at least 2 8 d a y s after t he last d ose of st u d y i nter ve nti o n, w hic h 
c orres p o n ds t o t he ti me nee de d t o eli mi nate re pr o d ucti ve safet y ris k of t he st u d y 
i nter ve nti o n(s): 

Refrai n fr o m d o nati n g s per m .
P L U S eit her :

Be a bsti ne nt fr o m heter ose x ual i nterc o urse as t heir preferre d a n d us ual lifest y le 
(a bsti ne nt o n a l o n g-ter m a n d persiste nt basis) a n d a gree t o re mai n a bsti ne nt.
O R

M ust a gree
t o use c o ntrace pti o n/ barrier as detaile d bel o w:

A gree t o use a male c o n d o m , a n d s h o ul d als o be a d vise d of t he be nefit f or a 
fe male part ner t o use a hi g hly effecti ve met h o d of c o ntrace pti o n , as a c o n d o m 
ma y  brea k or lea k, w he n ha vi n g se x ual i nterc o urse wit h a W O C B P
w h o is n ot 
c urre ntl y pre g na nt.

I n a d diti o n t o male c o n d o m use, a hi g hly effecti ve met h o d of c o ntrace pti o n ma y be 
c o nsi dere d i n W O C B P part ners of male partici pa nts (refer t o t he list of hi g hl y 
effecti ve met h o ds bel o w i n Secti o n 1 0. 4. 4 ).
1 0. 4. 2. Fe m ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
T he criteria bel o w are part of I ncl usi o n Criteri o n 1 ( A ge a n d Se x; Secti o n 5. 1 ) a n d s pecif y 
t he re pr o d ucti ve re q uire me nts f or i ncl u di n g fe male partici pa nts. Refer t o Secti o n 1 0. 4. 4 f or a 
c o m plete list of c o ntrace pti ve met h o ds per mitte d i n t he st u d y . 
A fe male partici pa nt is eli gi ble t o partici pate if s he is n ot pre g na nt or breastfee di n g a n d at 
least 1 of t he f oll o wi n g c o n diti o ns a p plies:

Is n ot a W O C B P (see defi niti o n i n Secti o n 1 0. 4. 3 ).
O R

Is a W O C B P a n d a grees t o use a hi g hly effecti ve c o ntrace pti ve met h o d (fail ure rate of 
< 1 % per ye ar) d uri n g t he i nter ve nti o n peri o d a n d f or at least 2 8 d a ys after t he last 
d ose of st u d y  i nter ve nti o n, w hic h c orres p o n ds t o t he ti me nee de d t o eli mi nate a n y 
re pr o d ucti ve safety ris k of t he st u d y i nter ve nti o n(s). If a hi g hl y effecti ve, user -
de pe n de nt met h o d is c h ose n, s he a grees t o c o nc urre ntl y  use a n effecti ve barrier 
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 1
met h o d of c o ntrace pti o n. T he i n vesti gat or s h o ul d e val uate t he effecti ve ness of t he 
c o ntrace pti ve met h o d i n relati o ns hi p t o t he first d ose of st u d y i nter ve nti o n.
O R

Is a W O C B P a n d a grees t o use a h i g hly effecti ve (fail ure rate of < 1 % per year) user -
de pe n de nt met h o d of c o ntrace pti o n d uri n g t he i nter ve nti o n peri o d a n d f or at least 2 8
da y s after t he last d ose of st u d y  i nter ve nti o n, w hic h c orres p o n ds t o t he ti me nee de d t o 
eli mi nate a n y re pr o d ucti ve safet y ris k of t he st u d y i nter ve nti o n(s).  I n a d diti o n t o her 
use of t he hi g hl y  effecti ve met h o d a b o ve, s he a grees t o c o nc urre ntl y use a n effecti ve 
barrier met h o d. T he i n vesti gat or s h o ul d e val uate t he effecti ve ness of t he 
c o ntrace pti ve met h o d i n relati o ns hi p t o t he first d ose of st u d y i nter ve nti o n.
T he i n vesti gat or is res p o nsi ble f or re vie w of me dical hist or y , me nstr ual hist or y, a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n early u n detecte d 
pre g na nc y .
1 0. 4. 3. W o m a n of C hil d be ari n g P ote nti al
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal 
u nless per ma ne ntl y sterile (see bel o w).
If fertilit y is u nclear (e g, a me n orr hea or oli g o me n orr hea ) a n d a me nstr ual c ycle ca n n ot be 
c o nfir me d bef ore t he first d ose of st u d y i nter ve nti o n, a d diti o nal e val uati o n s h o ul d be 
c o nsi dere d.
W o me n i n t he f oll o wi n g cate g ories are n ot c o nsi dere d W O C B P :
1.
Pre me n o pa usal fe male wit h 1 of t he f oll o wi n g:

D oc u me nte d h ys terect o m y;

D oc u me nte d bilateral sal pi n gect o m y ;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y  d ue t o a me dical ca use ot her t ha n t he a b o ve
(e g, m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y), i n vesti gat or discreti o n s h o ul d be a p plie d 
t o deter mi ni n g st u dy e ntr y.
N ote: D oc u me ntati o n f or a n y of t he a b o ve cate g ories ca n c o me fr o m t he site pers o n nel’s 
re vie w of t he partici pa nt’s me dical rec or ds, me dical e xa mi nati o n, or me dical hist or y 
i nter vie w. T he met h o d of d oc u me ntati o n s h o ul d be rec or de d i n t he partici pa nt’s me dical 
rec or d f or t he st u dy.
2.
P ost me n o pa usal fe male .
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 2

A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati ve me dical ca use. I n a d diti o n:

A h i g h F S H le vel i n t he p ost me n o pa usal ra n ge m ust be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n u n der 6 0 ye ars ol d a n d n ot usi n g h or m o nal 
c o ntrace pti o n or H R T. 

A f e male o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o 
use o ne of t he hi g hl y effecti ve n o nestr o ge n h or m o nal c o ntrace pti o n met h o ds 
if s he wis h es t o c o nti n ue her H R T d uri n g t he st u d y . Ot her wise, s he m ust 
disc o nti n ue H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y  
e nr oll me nt.
1 0. 4. 4. C o ntr ace pti o n Met h o ds
C o ntrace pti ve use b y me n or w o me n s h o ul d be c o nsiste nt wit h l ocal a vaila bilit y /re g ulati o ns 
re gar di n g t he use of c o ntrace pti ve met h o ds f or t h ose partici pati n g i n cli nical trials.
T he f oll o wi n g c o ntrace pti ve met h o ds are a p pr o priate f or t his st u d y :
Hi g hl y Effecti ve Met h o ds T hat H a ve L o w User De pe n de nc y 
1.
I m pla nta ble pr o gest o ge n-o nl y  h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n.
2.
I ntra uteri ne de vice.
3.
I ntra uteri ne h or m o ne-releasi n g sys te m.
4.
Bilateral t u bal occl usi o n.
5.
Vasect o mize d part ner.

Vasect o mize d part ner is a hi g hl y effecti ve c o ntrace pti ve met h o d pr o vi de d t hat t he 
part ner is t he s ole se x ual part ner of t he W O C B P a n d t he a bse nce of s per m has 
bee n c o nfir me d.  If n ot, a n a d diti o nal hi g hl y effecti ve met h o d of c o ntrace pti o n 
s h o ul d be use d.  T he s per mat o ge nesis c ycle is a p pr o xi matel y 9 0 da ys.
Hi g hl y Effecti ve Met h o ds T hat A re User D e pe n de nt 
1.
Pr o gest o ge n - o nly h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:

Oral + b arrier*

I njecta ble + b arrier*
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 3
Se x ual A bsti ne nce
1.
Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  if defi ne d as 
refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d 
wit h t he st u d y  i nter ve nti o n.  T he relia bilit y of se x ual a bsti ne nce nee ds t o be e valuate d 
i n relati o n t o t he d urati o n of t he st u d y a n d t he preferre d a n d us ual lifestyl e of t he 
partici pa nt .
* Acce pta ble barrier met h o ds t o be use d c o nc o mita ntl y wit h o pti o n 6 f or t he st u d y i ncl u de 
a n y of t he f oll o wi n g:

Male or fe male c o n d o m wit h or wit h o ut s per mici de;

Cer vical ca p, dia p hra g m , or s p o n ge wit h s per mici de;

A c o m bi nati o n of male c o n d o m wit h eit her cer vical ca p, dia p hra g m , or s p o n ge 
wit h s per mici de ( d o u ble -barrier met h o ds).
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 4
1 0. 5. A p pe n di x 5: Ge netics
Use/ A n al ysis of D N A

Ge netic variati o n ma y  i m pact a partici pa nt’s res p o nse t o st u d y  i nter ve nti o n, 
s usce pti bilit y t o, a n d se verit y a n d pr o gressi o n of disease. T heref ore, w here l ocal 
re g ulati o ns a n d I R Bs/ E Cs all o w, a bl o o d sa m ple will be c ollecte d f or D N A a nal ys is.

T he sc o pe of t he g e netic researc h ma y b e narr o w (e g, 1 or m ore ca n di date ge nes ) or
br oa d (e g, t he e ntire ge n o me), as a p pr o priate t o t he scie ntific q uesti o n u n der 
i n vesti gati o n.

T he sa m ples ma y  be a nal yze d as part of a m ultist u d y assess me nt of ge netic fact ors 
i n v ol ve d i n t he res p o nse t o sis u nat o vir or st u d y  i nter ve nti o ns of t his class t o 
u n dersta n d treat me nts f or t he disease(s) u n der st u d y  or t he disease(s) t he msel ves.

T he res ults of ge netic a nal y ses ma y be re p orte d i n t he C S R or i n a se parate st u d y 
s u m mar y, or ma y be use d f or i nter nal decisi o n ma ki n g wit h o ut bei n g i ncl u de d i n a 
st u d y re p ort.

T he s p o ns or will st ore t he D N A sa m ples i n a sec ure st ora ge s pace wit h a de q uate 
meas ures t o pr otect c o nfi de ntialit y . 

T he sa m ples will be retai ne d as i n dicate d:

Retai ne d s a m ples will be st ore d i n defi nitel y  or f or a not her peri o d as per l ocal 
re q uire me nts.  

Partici pa nt s ma y wit h dra w t heir c o nse nt f or t he st ora ge a n d/ or use of t heir Retai ne d 
Researc h Sa m ples at a n y ti me b y ma ki n g a re q uest t o t he i n vesti gat or; i n t his case, a ny 
re mai ni n g material will be destr oye d. Data alrea d y ge nerate d fr o m t he sa m ples will be 
retai ne d t o pr otect t he i nte grit y of e xisti n g a nalys es.  

Sa m ples f or ge netic researc h will be la bele d wit h a c o de. T he ke y  bet wee n t he c o de 
a n d t he partici pa nt ’s pers o nall y i de ntif yi n g i nf or mati o n (e g, name, a d dress) will be 
hel d sec urel y at t he st u d y site.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 5
1 0. 6. A p pe n di x 6: Li ver S afet y: S u g geste d Acti o ns a n d F oll o w- U p Assess me nts [ a n d 
St u d y I nter ve nti o n Rec h alle n ge G ui deli nes]
P ote nti al C ases of Dr u g -I n d uce d Li ver I nj ur y
H u ma ns e x p ose d t o a dr u g w h o s h o w n o si g n of li ver i nj ur y  (as deter mi ne d b y ele vati o ns i n 
tra nsa mi nases) are ter me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li ver i nj ur y b ut a da pt 
are ter me d “a da pt ors.” I n s o me partici pa nt s, tra nsa mi nase ele vati o ns are a har bi n ger of a 
m ore seri o us p ote ntial o utc o me. T hese partici pa nt s fail t o a da pt a n d t heref ore are 
“s usce pti ble” t o pr o gressi ve a n d seri o us li ver i nj ur y, c o m m o nly referre d t o as DI LI. 
Partici pa nt s w h o e x perie nce a tra nsa mi nase ele vati o n a b o ve 3 × U L N s h o ul d be m o nit ore d 
m ore fre q ue ntl y  t o deter mi ne if t he y are “a da pt ors” or are “s usce pti ble.”
I n t he maj orit y of DI LI cases, ele vati o ns i n A S T a n d/ or A L T prece de T bili ele vati o ns 
( > 2 × U L N) b y  se veral da ys or wee ks. T he i ncrease i n T b ili t ypicall y  occ urs w hile 
A S T/ A L T is/ar e still ele vate d a b o ve 3 × U L N (ie, A S T/ A L T a n d T b ili val ues will be 
ele vate d wit hi n t he sa me la b orat or y sa m ple). I n rare i nsta nces, b y t he ti me T b ili ele vati o ns 
are detecte d, A S T/ A L T val ues mi g ht ha ve decrease d. T his occ urre nce is still re gar de d as a 
p o te ntial DI LI. T heref ore, a b n or mal ele vati o ns i n eit her A S T O R A L T i n a d diti o n t o T b ili 
t hat meet t he criteria o utli ne d bel o w are c o nsi dere d p ote ntial DI LI (assesse d per H y’s la w 
criteria) cases a n d s h o ul d al wa ys be c o nsi dere d i m p orta nt me dical e ve nts, e ven bef ore all 
ot her p ossi ble ca uses of li ver i nj ur y  ha ve bee n e xcl u de d.
T he t hres h ol d of la b orat or y  a b n or malities f or a p ote ntial DI LI case de pe n ds o n t he 
partici pa nt ’s i n di vi d ual baseli ne val ues a n d u n derl yi n g c o n diti o ns. Partici pa nt s w h o prese nt 
wit h t he f oll o wi n g la b orat or y a b n or malities s h o ul d be e val uate d f urt her as p ote ntial DI LI 
( Hy’s la w) cases t o defi niti vel y  deter mi ne t he eti ol o g y of t he a b n or mal la b orat or y val ues:

Partici pa nt s wit h A S T/ A L T a n d T b ili baseli ne val ues wit hi n t he n or mal ra n ge w h o 
s u bse q ue ntl y prese nt wit h A S T O R A LT val ues ≥3 × U L N A N D a T b ili val ue ≥2 × U L N 
wit h n o e vi de nce of he m ol y sis a n d a n al kali ne p h os p hatase val ue < 2 × U L N or n ot 
a vaila ble.

F or partici pa nt s wit h baseli ne A S T O R A L T O R T b ili val ues a b o ve t he U L N, t he 
f oll o wi n g t hres h ol d val ues are use d i n t he defi niti o n me nti o ne d a b o ve, as nee de d, 
de pe n di n g o n w hic h val ues are a b o ve t he U L N at baseli ne:

Pree xisti n g A S T or A L T baseli ne val ues a b o ve t he n or mal ra n ge: A S T or A L T 
val ues ≥2 ti mes t he baseli ne val ues A N D ≥3 × U L N; or ≥8 × U L N ( w hic he ver is 
s maller).

Pree xisti n g val ues of T b ili a b o ve t he n or mal ra n ge: T b ili le vel i ncrease d fr o m 
baseli ne val ue b y a n a m o u nt of  ≥1 × U L N or if t he val ue reac hes ≥3 × U L N 
( w hic he ver is s maller).
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 6
Rises i n A S T/ A L T a n d T b ili se parate d b y m ore t ha n a fe w wee ks s h o ul d be assesse d 
i n di vi d uall y base d o n cli nical j u d g me nt; a n y case w here u ncertai nt y re mai ns as t o w het her it 
re prese nts a p ote ntial H y’s la w case s h o ul d be re vie we d wit h t he s p o ns or. 
T he partici pa nt s h o ul d ret ur n t o t he i n vesti gat or site a n d be e val uate d as s o o n as p ossi ble, 
prefera bl y wit hi n 4 8 h o urs fr o m a ware ness of t he a b n or mal res ults. T his e val uati o n s h o ul d 
i ncl u de la b orat or y tests, detaile d hist or y, a n d p h ysical assess me nt.
I n a d diti o n t o re peati n g meas ure me nts of A S T a n d A LT a n d T b ili f or s us pecte d H y ’s la w 
cases , a d diti o nal la b orat or y tests s h o ul d i ncl u de al b u mi n, C K, direct a n d i n direct bilir u bi n, 
G G T, P T/I N R, t otal bile aci ds, a n d al kali ne p h os p hatase. C o nsi derati o n s h o ul d als o be gi ve n 
t o dra wi n g a se parate t u be of cl otte d bl o o d a n d a n a ntic oa g ulate d t u be of bl o o d f or f urt her 
testi n g, as nee de d, f or f urt her c o nte m p ora ne o us a nal yses at t he ti me of t he rec o g nize d i nitial 
a b n or malities t o deter mi ne eti ol o g y . A detaile d hist or y, i ncl u di n g rele va nt i nf or matio n, s uc h 
as re vie w of et ha n ol, aceta mi n o p he n / paraceta m ol (eit her b y itself or as a c of or m ulate d 
pr o d uct i n prescri pti o n or o ver -t he-c o u nter me dicati o ns), recreati o nal dr u g, or s u p ple me nt 
( her bal) use a n d c o ns u m pti o n, fa mil y hist or y, se x ual hist or y, tra vel hist or y, hist or y  of c o ntact 
wit h a ja u n dice d pers o n, s ur ger y , bl o o d tra nsf usi o n, hist or y of li ver or aller gic disease, a n d 
p ote ntial occ u pati o nal e x p os ure t o c he micals, s h o ul d be c ollecte d. F urt her testi n g f or ac ute 
he patitis A, B, C, D, a n d E i nfecti o n , li ver i ma gi n g (e g, biliar y tract), a n d c ollecti o n of ser u m 
sa m ples f or aceta mi n o p he n/ paraceta m ol dr u g a n d/ or pr otei n a d d uct le vels ma y  be warra nte d. 
All cases de m o nstrate d o n re peat testi n g as meeti n g t he la b orat or y  criteria of A S T/ A LT a n d 
T b ili ele vati o n defi ne d a b o ve s h o ul d be c o nsi dere d p ote ntial DI LI ( H y’s la w) cases if n o 
ot her reas o n f or t he L F T a b n or malities has yet bee n f o u n d. S uc h p ote nti al DI LI ( H y’s l a w) 
c ases are t o be re p orte d as S A Es, irres pecti ve of a v ail a bilit y of all t he res ults of t he 
i n vesti g ati o ns perf or me d t o deter mi ne eti ol o g y of t he L F T a b n or m alities.
A p ote ntial DI LI ( H y ’s la w) case bec o mes a c o nfir me d case o nly after all res ults of 
reas o na ble i n vesti gati o ns ha ve bee n recei ve d a n d ha ve e xcl u de d a n alter nati ve eti ol o g y.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 7
1 0. 7. A p pe n di x 7: Ki d ne y S afet y: M o nit ori n g G ui deli nes
1 0. 7. 1. L a b or at or y Assess me nt of C h a n ge i n Ki d ne y F u ncti o n a n d Detecti o n of Ki d ne y 
I nj ur y
Sta n dar d ki d ne y  safet y m o nit ori n g re q uires assess me nt of baseli ne a n d p ost baseli ne Screat 
meas ure me nt t o esti mate ki d ne y  f u ncti o n [ Screat-base d e G F R] or creati ni ne cleara nce 
[e Cr Cl]). O btai ni n g Scree ni n g or Baseli ne Sc ys a n d p ost baseli ne refle x Sc ys (if c onfir me d 
Screat i ncrease ≥0. 3 m g/ d L ) ma kes it feasi ble t o disti n g uis h A KI fr o m DICI . If Screat 
i ncrease is c o nfir me d after baseli ne, t he n refle x meas ure me nt of Sc y s is i n dicate d (f or a d ult 
a n d f or pe diatric partici pa nts):
A D U L T S: C urre ntl y, 2 0 2 1 C K D -E PI  e G F R e q uati o ns ( Screat o nl y-base d a n d c o m bi ne d 
Screat pl us Sc y s-base d) are vali d f or use i n a d ults o nl y . At baseli ne Screat a n d Sc ys val ues 
are nee de d t o calc ulate 2 0 2 1 C K D- E PI  e G F R b y Screat o nly- base d e q uati o n (see Ta ble 
1 0. 7. 2. 1.) a n d b y c o m bi ne d Screat pl us Sc ys -base d e q uati o n. W he n p ost -baseli ne Screat 
i ncrease ≥0. 3 m g/ d L is c o nfir me d, t he n refle x Sc ys meas ure me nt is nee de d t o e na ble p ost -
baseli ne c o m paris o n of e G F R c ha n ges ( Screat o nl y - base d e G F R a n d c o m bi ne d Screat pl us 
Sc y s e G F R). 
P E DI A T RI C S: C urre ntl y, n o Screat pl us Sc y s e G F R e q uati o ns ha ve bee n u ni versall y 
a d o pte d f or pe diatrics. T heref ore, c o m paris o n of baseli ne Scr eat a n d Sc ys t o p ost-baseli ne 
Screat a n d refle x Sc y s are utilize d t o s u p p ort differe ntiati o n of A KI fr o m DI KI. Re gar dless 
of w het her ki d ne y  f u ncti o n m o nit ori n g tests are re q uire d as a r o uti ne safety m o nit ori n g 
pr oce d ure i n t he st u d y , if t he i n vesti gat or or s p o ns or dee ms it necessar y t o f urt her assess 
ki d ne y  safety a n d q ua ntif y ki d ne y  f u ncti o n, t he n t hese test res ults s h o ul d be ma na ge d a n d 
f oll o we d per sta n dar d of care.
1 0. 7. 2. A ge -S pecific Ki d ne y F u ncti o n C alc ul ati o n Rec o m me n d ati o ns
1 0. 7. 2. 1. A d ults ( 1 8 Y e ars a n d A b o ve) — 2 0 2 1 C K D- E P I E q u ati o ns
e G F R ( m L/ mi n/ 1. 7 3 m²) 1 2
2 0 2 1 C K D -
E PI            
Scr e at O nl y
Scr e at
( m g/ d L)
Sc ys
( m g/ L)
Rec o m me n de d e G F R E q u ati o n
Fe male
if ≤ 0. 7
N/ A
e G F R = 1 4 3 × ( Scr eat/ 0. 7)-0. 2 4 1  ×  ( 0. 9 9 3 8) A ge
Fe male
if > 0. 7
N/ A
e G F R = 1 4 3 × ( Scr eat/ 0. 7)-1. 2 0 0  ×  ( 0. 9 9 3 8) A ge
Male
if ≤ 0. 9
N/ A
e G F R = 1 4 2 × ( Scr eat/ 0. 9)-0. 3 0 2  ×  ( 0. 9 9 3 8) A ge
Male
if > 0. 9
N/ A
e G F R = 1 4 2 × ( Scr eat/ 0. 9)-1. 2 0 0  ×  ( 0. 9 9 3 8) A ge
2 0 2 1 C K D -
E PI           
Scr e at-Sc ys 
C o m bi ne d
Scr e at
( m g/ d L)
Sc ys
( m g/ L)
Rec o m me n de d e G F R E q u ati o n
Fe male
if ≤ 0. 7
if ≤ 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 2 1 9  ×
( Sc ys/ 0. 8)- 0. 3 2 3  ×
( 0. 9 9 6 1)A ge
Fe male
if ≤ 0. 7
if > 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 2 1 9  ×
( Sc ys/ 0. 8)- 0. 7 7 8  ×
( 0. 9 9 6 1)A ge
Fe male
if > 0. 7
if ≤ 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 5 4 4  ×
( Sc ys/ 0. 8)- 0. 3 2 3  ×
( 0. 9 9 6 1)A ge
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 8
Fe male
if > 0. 7
if > 0. 8
e G F R = 1 3 0 × ( Scr eat/ 0. 7)-0. 5 4 4  ×
( Sc ys/ 0. 8)- 0. 7 7 8  ×
( 0. 9 9 6 1)A ge
Male
if ≤ 0. 9
if ≤ 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 1 4 4  ×
( Sc ys/ 0. 8)- 0. 3 2 3  ×
( 0. 9 9 6 1)A ge
Male
if ≤ 0. 9
if > 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 1 4 4  ×
( Sc ys/ 0. 8)- 0. 7 7 8  ×
( 0. 9 9 6 1)A ge
Male
if > 0. 9
if ≤ 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 5 4 4  ×   ( Sc ys/ 0. 8)- 0. 3 2 3  ×
( 0. 9 9 6 1)A ge
Male
if > 0. 9
if > 0. 8
e G F R = 1 3 5 × ( Scr eat/ 0. 9)-0. 5 4 4  ×   ( Sc ys/ 0. 8)- 0. 7 7 8  ×
( 0. 9 9 6 1)A ge
1 0. 7. 2. 2. A d olesce nts ( 1 2 Ye ars t o < 1 8 Ye ars) — C oc kcr oft -G a ult F or m ul a
e Cr Cl ( m L/ mi n) 
Males:  e Cr Cl = [( 1 4 0 -
a ge) × b o d y wei g ht (i n k g)] / [ Screat (i n m g/ d L) × 7 2]
Fe males: e Cr Cl = 0. 8 5 × [( 1 4 0 - a ge) × b o d y wei g ht (i n k g)] / [ Screat (i n m g/ d L) × 7 2]
1 0. 7. 2. 3. C hil dre n ( 2 Ye ars t o < 1 2 Ye ars) —
Sc h w artz E q u ati o n
e Cr Cl n or malize d t o B S A ( m L/ mi n/ 1. 7 3 m2) 
e Cr Cl = ( K × Ht) / Screat
Ht i n c m; Screat i n m g/ d L.
K ( pr o p orti o nalit y  c o nsta nt): Fe male c hil d < 1 2 years: K = 0. 5 5. Male c hil d < 1 2 years: K = 
0. 7 0.
1 0. 7. 2. 4. I nf a nts ( 1 M o nt h t o < 2 Ye ars) a n d Ne o n ates ( < 1 M o nt h) — S c h w artz E q u ati o n
e G F R ( m L/ mi n/ 1. 7 3 m 2) = 0. 4 1 3 × ( Ht/ Screat)
Ht i n c m; Screat i n m g/ d L.
1 0. 7. 3. Ki d ne y F u ncti o n C alc ul ati o n T o ols
T he s p o ns or has pr o vi de d t he f oll o wi n g res o urces t o i n vesti gati o nal sites w he n re q uire d t o 
calc ulate a ge -s pecific ki d ne y f u ncti o n at Scree ni n g, Baseli ne, a n d p ost-Baseli ne visits. Site 
calc ulati o ns of ki d ne y f u ncti o n ca n be perf or me d ma n uall y, usi n g t he a ge a p pr o priate 
f or m ulae (see Secti o n 1 0. 7. 2 ) a n d ca n use rec o m me n de d o nli ne ki d ne y f u ncti o n calc ulat ors 
t o re d uce t he li keli h o o d of a calc ulati o n err or. 
T he U nite d States Nati o nal Ki d ne y  F o u n dati o n O nli ne Calc ulat ors. 

A d ults ( 1 8 y ears a n d a b o ve) - 2 0 2 1 C K D -E PI  Creati ni ne O nli ne Calc ulat or (e G F R): 
htt ps:// w w w. ki d ne y . or g/ pr ofessi o nals/ K D O QI/ gfr _calc ulat or

A d olesce nts ( 1 2 ye ars t o < 1 8 years) - C oc kcr oft -Ga ult F or m ula (e Cr Cl): 
htt ps:// w w w. ki d ne y . or g/ pr ofessi o nals/ k d o qi/ gfr _calc ulat or C oc
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 9 9
I n vesti gati o nal sites are res p o nsi ble t o e ns ure t hat t he acc urate a ge -s pecific e q uati o n is 
selecte d a n d t hat t he c orrect u nits f or ser u m creati ni ne ( m g/ d L o nly), ser u m c ystati n C ( m g/ L 
o nl y ), t otal b o dy wei g ht ( k g o nl y), a n d a ge ( y ears). In vesti gat ors are e x pecte d t o (i) re vie w 
an d c o nfir m c orrect ness of t he ki d ne y  f u ncti o n calc ulati o n res ults a n d (ii) e val uate t he 
calc ulate d val ue wit hi n t he c o nte xt of hist orical i nf or mati o n a vaila ble t o t he m i n t he 
partici pa nt’s me dical rec or d. I n vesti gat ors are res p o nsi ble f or t he cli nical o ver si g ht of t he 
partici pa nt eli gi bilit y  pr ocess, ki d ne y f u ncti o n calc ulati o n, a n d d ose selecti o n a n d 
a dj ust me nts per st u d y pr ot oc ol. In vesti gat ors are e nc o ura ge d t o direct q uesti o ns or 
u ncertai nties re gar di n g ki d ne y  f u ncti o n a n d d osi n g t o t he Pfizer Cli nical Tea m a n d Me dical 
M o nit or, if nee de d.
1 0. 7. 4. A d verse E ve nt Gr a di n g f or Ki d ne y S afet y L a b or at or y A b n or m alities
A E gra di n g f or decli ne i n ki d ne y f u ncti o n (ie, e G F R or e Cr Cl) will be acc or di n g t o Ki d ne y  
Disease: I m pr o vi n g Gl o bal O utc o mes ( K DI G O) criteria.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 0
1 0. 8. A p pe n d i x 8 : E C G Fi n di n gs of P ote nti al Cli nic al C o ncer n
E C G Fi n di n gs T h at M a y Q u alif y as A Es

Mar ke d si n us b ra dyc ar dia (rate < 4 0 b p m) lasti n g mi n utes .

Ne w P R i nter val pr ol o n gati o n > 2 8 0 ms.

Ne w pr ol o n gati o n of Q Tc F t o > 4 8 0 ms (a bs ol ute).

Ne w pr ol o n gati o n of Q Tc F b y  > 6 0 ms fr o m baseli ne.

Ne w - onset atrial fl utter or fi brillati o n, wit h c o ntr olle d ve ntric ular res p o nse rate: ie, 
rate < 1 2 0 b p m .

Ne w - onset ty pe I sec o n d - de gree ( We nc ke bac h) A V b l oc k of > 3 0 sec o n ds
d urati o n .

Fre q ue nt P V Cs, tri plets, or s h ort i nter vals ( < 3 0 sec o n ds) of c o nsec uti ve 
ve ntric ular c o m ple xes.
E C G Fi n di n gs T h at M a y Q u alif y as S A Es

Q Tc F pr ol o n gati o n > 5 0 0 ms .

A bs ol ute val ue of Q Tc F > 4 5 0 ms A N D Q Tc F c ha n ge fr o m baseli ne > 6 0 ms.

Ne w S T -T c ha n ges s u g gesti ve of m y ocar dial isc he mia .

Ne w - onset L B B B ( Q R S c o m ple x > 1 2 0 ms) .

Ne w - onset ri g ht b u n dle b ra nc h b l oc k ( Q R S c o m ple x > 1 2 0 ms) .

S y m pt o matic b ra dyc ar dia.

As y st ole:

I n a wa ke, sy m pt o m -free partici pa nt s i n si n us r h yt h m, wit h d oc u me nte d 
as yst olic pa uses ≥3 sec o n ds or a ny esca pe rate < 4 0 b p m, or wit h a n esca pe 
r h yt h m t hat is bel o w t he A V n o de. 

I n a wa ke, sy m pt o m -free partici pa nt s wit h atrial fi brillati o n a n d bra d yc ar dia 
wit h 1 or m ore as ys t olic pa uses of at least 5 sec o n ds or l o n ger. 

Atrial fl utter or fi brillati o n, wit h ra pi d ve ntric ular res p o nse rate: ra pi d = rate 
> 1 2 0 b p m.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 1

S ustai ne d su pra ve ntric ular tac h yc ar dia (rate > 1 2 0 b p m) ( “s ustai ne d” = s h ort 
d urati o n wit h rele va nt s y m pt o ms or lasti n g > 1 mi n ute) .

Ve ntric ular r h y t h ms > 3 0 sec o n ds’ d urati o n, i ncl u di n g i di o ve ntric ular r h y t h m (H R
< 4 0 b p m), accelerate d i di o ve ntric ular r h yt h m ( H R > 4 0 b p m t o < 1 0 0 b p m), a n d 
m o n o m or p hic/ p ol y m or p hic ve ntric ular tac h ycar dia ( H R > 1 0 0 b p m [s uc h as
torsa des de p oi ntes ]).

T y pe II sec o n d- de gree ( M o bitz II) A V b l oc k.

C o m plete (t hir d- de gree) h eart b l oc k.
E C G F i n di n gs T h at Q u alif y as S A Es

C ha n ge i n patter n s u g gesti ve of ne w m y ocar dial i nfarcti o n .

S ustai ne d v e ntric ular ta c h yarr h yt h mias ( > 3 0 sec o n d d urati o n).

Sec o n d - or t hir d - de gree A V bl oc k re q uiri n g pace ma ker place me nt.

As y st olic pa uses re q uiri n g pace ma ker place me nt .

Atrial fl utter or fi brillati o n wit h ra pi d ve ntric ular res p o nse re q uiri n g car di o versi o n .

Ve ntric ular fi brillati o n/fl utter.

At t he discreti o n of t he i n vesti gat or, a n y arr h yt h mia classifie d as a n a d verse 
e x perie nce.
T he maj or e ve nts of p ote ntial c li nical c o ncer n liste d a b o ve are rec o m me n de d as “alerts” or n otificati o ns 
fr o m t he c ore E C G la borat or y t o t he i n vesti gat or a n d Pfizer st u d y tea m, a n d n ot t o be c o nsi dere d as all-
i ncl usi ve of w hat is t o be re p orte d as A Es/ S A Es.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 2
1 0. 9. A p pe n di x 9 : Pr o hi bite d C o nc o mit a nt Me dic ati o ns T h at M a y Res ult i n D DI  
T he pr o hi bite d c o nc o mita nt me dicati o ns liste d bel o w a n d a nti bi otics s h o ul d n ot be ta ke n wit h 
sis u nat o vir f or t he peri o d of ti me at least e q ual t o 5 half -li ves pl us 1 4 da ys prece di n g t he first 
d ose of st u d y  i nter ve nti o n, a n d t hr o u g h o ut t he c o n d uct of t he st u d y. A d diti o nall y , preca uti o n 
s h o ul d be ma de t o e ns ure t hat n o c o n me ds t hat pr ol o n g Q T or Q Tc are a d mi nistere d t o 
partici pa nts.
T he Pfizer st u d y tea m is t o be n otifie d of a n y  pr o hi bite d me dicati o ns ta ke n d uri n g t he st u dy. 
After c o ns ulti n g wit h t he s p o ns or, t he i n vesti gat or will ma ke a j u d g me nt o n t he o n g oi n g 
partici pati o n of a n y partici pa nt wit h pr o hi bite d me dicati o n use d uri n g t he st u d y.
T his list of dr u gs pr o hi bite d f or p ote ntial D DI c o ncer ns wit h t he I M P ma y  be re vise d d uri n g 
t he c o urse of t he st u d y wit h writte n n otificati o n fr o m s p o ns or, t o i ncl u de or e xcl u de s pecific 
dr u gs or dr u g cate g ories f or vari o us reas o ns (e g, e mer gi n g D DI res ults f or t he I M P, 
a vaila bilit y of ne w i nf or mati o n i n literat ure o n t he D DI p ote ntial of ot her dr u gs) , if t he 
o verall be nefit:ris k assess me nt is n ot i m pacte d or if t he c ha n ges d o n ot si g nifica ntl y  i m pact  
t he safety of partici pa nts or t he scie ntific val ue of t he trial  
Str o n g a n d m o derate C Y P 3 A 4 a n d P -g p i n hi bit ors or i n d ucers are pr o hi bite d, as t hese 
me dicati o ns ma y  ha ve mea ni n gf ul i m pact o n t he p har mac o ki netics of sis u nat o vir.
Sis u nat o vir is a C Y P 3 A 4 i n hi bit or a n d t heref ore se nsiti ve a n d narr o w t hera pe utic i n de x 
C Y P 3 A 4 s u bstrates are als o pr o hi bite d i n t his st u d y . Since base d o n i n vitr o data sis u nat o vir
ma y  be a wea k i n hi bit or of  
, se nsiti ve narr o w TI s u bstrates of  
 are 
e xcl u de d.
Sis u nat o vir als o ma y be a n i n hi bit or of  
 a n d  
 tra ns p orters; t heref ore, se nsiti ve 
s u bstrates of t hese tra ns p orters are e xcl u de d.
Alt h o u g h his is n ot all- i ncl usi ve, a list of me dicati o ns t hat are pr o hi bite d i n t his st u d y is 
pr o vi de d bel o w. Site staff s h o ul d c o ns ult wit h t he s p o ns or or desi g nee wit h a n y  q uesti o ns 
re gar di n g p ote ntial D DI.
I n vesti gat ors s h o ul d c o ns ult t he pr o duct la bel f or a n y  ot her me dicati o n use d d uri n g t he st u d y 
f or i nf or mati o n re gar di n g me dicati o n t hat is pr o hi bite d f or c o nc o mita nt use.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 3
Pr o hi bite d C o nc o mit a nt Me dic ati o ns
C Y P 3 A I n hi bit ors
C Y P 3 A I n d ucers
M o der ate
Str o n g
M o der ate
Str o n g
A pre pita nt
B oce pre vir
B ose nta n
A pal uta mi de
Ci pr ofl o xaci n
C o bicistat
Efa vire nz
Car ba maze pi ne
C o ni va pta n
Da n o pre vir
Etra viri ne
E nzal uta mi de
Criz oti ni b
Dasa b u vir
P he n o bar bital
Mit ota ne
C y cl os p ori ne
El vite gra vir
Pri mi d o ne
P he n yt oi n
Diltiaze m
I n di na vir
Rifa m pi n
Dr o ne dar o ne
Itrac o naz ole
St. J o h n’s w ort
Er yt hr o m yci n
Ket oc o naz ole
Fl uc o naz ole
L o pi na vir
Fl u v o xa mi ne
Parita pre vir
I mati ni b
O m bitas vir
T ofis o pa m
P osac o naz ole
Vera pa mil
Rit o na vir
Sa q ui na vir
Tela pre vir
Ti pra na vir
Telit hr o m yci n
Tr olea n d o m yci n
V oric o naz ole
Se nsiti ve C Y P 3 A S u bstr ates
C Y P 3 A S u bstr ates 
wit h N arr o w T her a pe utic I n de x
Al fe nta nil
L o vastati n
Al fe nta nil
At or vastati n
L urasi d o ne
Aste miz ole
A va nafil
Mara vir oc
Cisa pri de
B u des o ni de
Mi daz ola m
C y cl os p ori ne
B us pir o ne
Nal o xe g ol
Di h y dr oer g ota mi ne
Darife naci n
Nis ol di pi ne
Er g ota mi ne
Dar u na vir
Q uetia pi ne
Fe nta n yl
Dasati ni b
Sil de nafil
Pi m ozi de
Dr o ne dar o ne
Si m vastati n
Q ui ni di ne
E basti ne
Sir oli m us
Sir oli m us
Eletri pta n
Tacr oli m us
Tacr oli m us
E plere n o ne
Tica grel or
Terfe na di ne
E ver oli m us
T ol va pta n
I br uti ni b
Ti pra na vir
I n di na vir
Triaz ola m
Fel o di pi ne
Var de nafil
L o mita pi de
 
P- g p I n hi bit ors
P- g p I n d ucers
Ataza na vir
L o pi na vir
A pal uta mi de
B oce pre vir
L u macaft or
Ataza na vir
C o bicistat
Mife prist o ne
F osa m pre na vir
C o ni va pta n
Nelfi na vir
L o pi na vir
C y cl os p ori ne
o m bitas vir a n d parita pre vir 
a n d rit o na vir a n d dasa b u vir
Rifa m pi n
Dar u na vir
P osac o naz ole
St. J o h n’s w ort ( h y peric u m perf orat u m) e xtract
Diltiaze m
Rit o na vir
Ti pra na vir
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 4
el vite gra vir a n d c o bicistat 
a n d e mtricita bi ne a n d 
te n of o vir D F
Sa q ui na vir
Vera pa mil
Er yt hr o m yci n
Tela pre vir
gleca pre vir a n d pi bre ntas vir
Ti pra na vir
I n di na vir
T ucati ni b
Itrac o naz ole
Vera pa mil
Ket oc o naz ole
v o n o praza n a n d a m o xicilli n 
a n d clarit hr o m yci n
L o nafar ni b
V o xila pre vir
N ot a n all -i ncl usi ve list.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 5
1 0. 1 0. A p pe n di x 1 0 : A b bre vi ati o ns
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y  be use d i n t he pr ot oc ol. 
A b bre vi ati o n
Ter m
A bs
a bs ol ute
A D L
acti vit y/ acti vities of dail y li vi n g
A D M E
A bs or pti o n Distri b uti o n Meta b olis m E xcreti o n
A E
a d verse e ve nt
A L T
ala ni ne a mi n otra nsferase
A P D 9 0
acti o n p ote ntial d urati o n at 9 0 % re p olarizati o n
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c ur ve
A U C ta u
area u n der t he c ur ve fr o m zer o ti me t o ti me ta u, t he d osi n g i nter val
A V
atri o ve ntric ular
A x M P
a u xiliar y me dici nal pr o d uct
Bal b/ C
al bi n o, la b orat or y-bre d strai n of t he h o use m o use
B B S
Bi os peci me n Ba n ki n g S yste m
-h C G
-h u ma n c h ori o nic g o na d otr o pi n
B MI
b o d y  mass i n de x
B P
bl o o d press ure
b p m
beats per mi n ute
Ca v
A vera ge C o nce ntrati o n D uri n g a D osi n g I nter val
C F R
C o de of Fe deral Re g ulati o ns
CI
C o nfi de nce I nter vals
CI O M S
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces
C K
creati ne ki nase
C K D -E PI
c hr o nic ki d ne y disease e pi de mi ol o g y
C L
c o m p uls or y lice nse
C ma x
ma xi m u m o bser ve d c o nce ntrati o n
C O 2
car b o n di o xi de ( bicar b o nate)
C O VI D -1 9
c or o na vir us disease 2 0 1 9
C Q T
Critical -T o -Q ualit y
C R F
case re p ort f or m
C R O
c o ntract researc h or ga nizati o n
C R U
cli nical researc h u nit
C S R
Cli nical St u d y  Re p ort
C T
cli nical trial
C TI S
Cli nical Trial I nf or mati o n S y ste m
C T M S
Cli nical Trial Ma na ge me nt S y ste m
C T S A E
ca ne t oa d s ki n a q ue o us e xtracts
C V
cardi o vasc ular
C Y P
c yt oc hr o me P 4 5 0
D C T
data c ollecti o n t o ol
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 6
A b bre vi ati o n
Ter m
D DI
dr u g -dr u g i nteracti o n 
DI C
De via nce I nf or mati o n Criteri o n
DI CI
dr u g -i n d uce d creati ni ne i ncrease
DI LI
dr u g -i n d uce d li ver i nj ur y
D P B
Diff use pa n br o nc hi olitis
D U
dis pe nsa ble u nit
E C
et hics c o m mittee
E C C
e mer ge nc y c o ntact car d
E C G
electr ocar di o gra m or electr ocar di o gra p h y
E T
earl y ter mi nati o n
e Cr Cl
esti mate d creati ni ne cleara nce
e C R F
electr o nic case re p ort f or m
E D B
e x p os ure d uri n g breastfee di n g
E -D M C
E xter nal Data M o nit ori n g C o m mittee
E D P
e x p os ure d uri n g pre g na nc y
e G F R
esti mate d gl o mer ular filtrati o n rate
E G F R
e pi der mal gr o wt h fact or rece pt or
E O T
en d of treat me nt
e S A E
electr o nic seri o us a d verse e ve nt
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n U ni o n Dr u g Re g ulati n g A ut h orities Cli n ical Trials 
(E ur o pea n Cli nical Trials Data base )
FI H
first i n h u ma n
F S H
f ollicle-sti m ulati n g h or m o ne
F/ U
f oll o w-u p
Ga m ma -G T
Ga m ma -gl uta m yl  tra ns pe pti dase
G C P
G o o d Cli nical Practice
G F R
Gl o mer ular filtrati o n rate
G G T
ga m ma -gl uta m y l tra nsferase
GI
gastr oi ntesti nal
G L P
Pri nci ples of G o o d La b orat or y  Practice
H Bc A b
he patitis B c ore a nti b o d y
H Bs A b
he patitis B s urface a nti b o d y
H Bs A g 
he patitis B s urface a nti ge n
H C V A b
he patitis C a nti b o d y
h E R G
t he h u ma n Et her-à-g o -g o -Relate d Ge ne
hI P S C -C M
H u ma n i n d uce d pl uri p ote nt ste m cell deri ve d car di o m y o c y tes
HI V
h u ma n i m m u n o deficie nc y vir us
H R
heart rate
H R T
h or m o ne re place me nt t hera p y
I B
I n vesti gat or’s Br oc h ure
I C D
i nf or me d c o nse nt d oc u me nt
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 7
A b bre vi ati o n
Ter m
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical 
Re q uire me nts f or P har mace uticals f or H u ma n Use
I D
i de ntificati o n
I M P
i n vesti gati o nal me dici nal pr o d uct
I ND
I n vesti gati o nal Ne w Dr u g 
I N R
i nter nati o nal n or malize d rati o
I P A L
I n vesti gati o nal Pr o d uct Acc o u nta bilit y L o g
I RB
I nstit uti o nal Re vie w B oar d
I V
I ntra ve n o us(ly)
K DI G O
Ki d ne y  Disease I m pr o vi n g Gl o bal O utc o mes
Ki
K u p per ma n I n de x
L B B B
left b u n dle bra nc h bl oc k
L F T
li ver f u ncti o n test
L R TI
L o wer Res pirat or y  Tract I nfecti o ns
L V
left ve ntricle
L V S P
Left ve ntric ular se ptal paci n g
M A D
Mitral a n n ul us disj u ncti o n
M M R M
mi xe d m o del f or re peate d meas ures
M QI
me dicall y  q ualifie d i n di vi d ual
M T D
ma xi m u m t olerate d d ose
N A
n ot a p plica ble
Na v
Ner ve Acti o n P ote ntial
NI M P
n o ni n vesti gati o nal me dici nal pr o d uct
N O A E L
n o -o bser ve d -a d verse-effect le vel
P C R U
Pfizer Cli nical Researc h U nit
P D
p har mac o d y n a mic(s)
% C V
perce nt c oefficie nt of variati o n
P -g p
per mea bilit y  glyc o pr otei n
P G x 
p har mac o ge n o mic(s)
P K
p har mac o ki netic(s)
P Q
Perf or ma nce Q ualificati o n
P R
p ulse rate
P S S A
Pfizer's Seri o us A d verse E ve nt S u b missi o n Assista nt
P T
pr ot hr o m bi n ti me
P V C
pre mat ure ve ntric ular c o ntracti o n/c o m ple x
Q
e ver y q ua ntit y
Q R S
Q R S c o m ple x , re prese nts ve ntric ular de p olarizati o n
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 8
A b bre vi ati o n
Ter m
Q T
Q T i nter val is t he ti me fr o m t he start of t he Q wa ve t o t he e n d of 
t he T wa ve
Q Tc
c orrecte d Q T i nter val
Q Tc B
Q T c orrecte d f or heart rate
Q Tc F
Q Tc c orrecte d usi n g Fri dericia’s f or m ula
Q Tc V
Q T c o n d ucti o n vel ocit y
q ual
q ualitati ve
Q & As
q uesti o ns a n d a ns wers
R B C
re d bl o o d cell
R R
Res pirati o n rate
R S V
Res pirat or y  S yn c y tial Vir us
R S V -F
T he res pirat or y  sy nc yt ial vir us F gl yc o pr otei n
S A D
Seas o nal affecti ve dis or der
S A E
seri o us a d verse e ve nt
S A P
Statistical A nal y sis Pla n
S A R S -C o V -2
se vere ac ute res pirat or y s yn dr o me c or o na vir us 2
Sc y s
ser u m c ystati n C
S o A
sc he d ule of acti vities
S O C
S pecialist O ut patie nt Cli nic
S O P
sta n dar d o perati n g pr oce d ure
S R S D
Si n gle Refere nce Safet y D oc u me nt
S T -T
S T -se g me nt a n d T-wa ve
S U S A R
S us pecte d U ne x pecte d Seri o us A d verse Reacti o n
T bili
t otal bilir u bi n
T d P
T orsa des de p oi ntes
T E A E
Treat me nt e mer ge nt a d verse e ve nts
T H C
tetra hy dr oca n na bi n ol
TI
t hera pe utic i n de x
T ma x
Ti me t o pea k dr u g c o nce ntrati o n
T Q T
T otal Q ualit y  Tra nsf or mati o n
U L N
u p per li mit of n or mal
U S
U nite d States
U S PI
U nite d States Prescri bi n g I nf or mati o n
U TI
uri nar y  tract i nfecti o n
W B C
w hite bl o o d cell
W O C B P
w o ma n/ w o me n of c hil d beari n g p ote ntial
yc A P D 9 0
yc  A P d urati o ns at 9 0 % re p olarizati o n
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)

P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 9
1 1. R E F E R E N C E S
1
Si m oes E A F, B o nt L, Ma nz o ni P, et al. Past, Prese nt a n d F ut ure A p pr oac hes t o t he 
Pre ve nti o n a n d Treat me nt of Res pirat or y  S yn c y tial Vir us Infecti o n i n C hil dre n. I nfect 
Dis T her. 2 0 1 8; 7( 1): 8 7 -1 2 0.
2
Li Y, Wa n g X, Bla u D M, et al. Gl o bal, re gi o nal, a n d nati o nal disease b ur de n esti mates 
of ac ute l o wer res pirat or y i nfecti o ns d ue t o res pirat or y s y n c ytial vir us i n c hil dre n 
y o u n ger t ha n 5 y ears i n 2 0 1 9: a s yste matic a nalys is. La ncet. 2 0 2 2; 3 9 9( 1 0 3 4 0): 2 0 4 7 -
2 0 6 4.
3
R ha B, C ur ns A T, Li vel y J Y, et al. Res pirat or y S y nc yt ial Vir us-Ass ociate d 
H os pitalizati o ns A m o n g Y o u n g C hil dre n: 2 0 1 5 -2 0 1 6. Pe diatrics. 2 0 2 0; 1 4 6( 1).
4
La n gle y  J M, Bia nc o V, D o mac h o ws ke J B, et al. I nci de nce of Res pirat or y S yn c y tial 
Vir us L o wer Res pirat or y Tract I nfecti o ns D uri n g t he First 2 Years of Life: A 
Pr os pecti ve St u d y  Acr oss Di verse Gl o bal Setti n gs. J Infect Dis. 2 0 2 2; 2 2 6( 3): 3 7 4 - 3 8 5.
5
J ha A, Jar vis H, Fraser C, O pe ns ha w PJ M. Res pirat or y Sy n c ytial Vir us. I n: H ui D S, 
R ossi G A, J o h nst o n S L , e ds. S A R S, M E R S a n d ot her Viral L u n g I nfecti o ns. S heffiel d 
( UK) 2 0 1 6.
6
Ki m L , R ha B, A bra ms o n J S, et al. Ide ntif y i n g Ga ps i n Res pirat or y S yn c y tial Vir us 
Disease E pi de mi ol o g y  i n t he U nite d States Pri or t o t he Intr o d ucti o n of Vacci nes. Cli n 
I nfect Dis. 2 0 1 7; 6 5( 6): 1 0 2 0- 1 0 2 5.
7
I C H E 1 4 G ui deli ne: t he cli nical e val uatio n of Q T/ Q Tc i nter val pr ol o n gati o n a n d 
prarr h yt h mic p ote ntial f or n o n -a ntiarr h yt h mic dr u gs, Q & As ( R 3); 1 0 Dec 2 0 1 5.
8
Lettieri, J., Var gas, R., A gar wal, V. et al. Effect of F o o d o n t he P har mac o ki netics of a 
Si n gle Oral D ose of M o xifl o xaci n 4 0 0 m g i n Healt h y  Male V ol u nteers.
Cli n 
P h ar m ac oki net 4 0 ( S u p pl 1), 1 9– 2 5 ( 2 0 0 1).
9
Ta u bel J, Fer ber G, L orc h U, Batc h var o v V, Sa velie va I, Ca m m AJ. T h or o u g h Q T st u d y  
of t he effect of oral m o xifl o xaci n o n Q Tc i nter val i n t he fe d a n d faste d state i n healt h y  
Ja pa nese a n d Ca ucasia n s u bjects. Br J Cli n P har mac ol. 2 0 1 4 Ja n; 7 7( 1): 1 7 0 - 9.
1 0
Mease P, Hall S, Fitz Geral d O, et al, T ofaciti ni b or A dali m u ma b vers us Place b o f or 
Ps oriatic Art hritis. N E n gl J Me d. 2 0 1 7 Oct 1 9; 3 7 7( 1 6): 1 5 3 7 - 5 0.
1 1
Gar nett C., et al. Scie ntific w hite pa per o n c o nce ntrati o n- Q Tc m o deli n g. J o ur nal of 
P har mac o ki net a n d P har mac o d y n Dece m ber 2 0 1 7; htt ps:// d oi. or g/ 1 0. 1 0 0 7/s 1 0 9 2 8 - 0 1 7-
9 5 5 8- 5 .
1 2
I n ker L A, E nea nya  N D, C ores h J, et al. Ne w Creati ni ne- a n d C ystati n C-Base d 
E q uati o ns t o Esti mate G F R wit h o ut Race. N E n gl J Me d. 2 0 2 1; 3 8 5( 1 9): 1 7 3 7 - 4 9.
                                                
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)