A PHASE 1, RANDOMIZED, OPEN-LABEL, 2-PART CROSSOVER STUDY TO ASSESS THE RELATIVE BIOAVAILABILITY OF SISUNATOVIR FOLLOWING SINGLE ORAL DOSE OF DIFFERENT FORMULATIONS UNDER FED AND FASTED CONDITIONS IN HEALTHY ADULT PARTICIPANTS
Phase: PHASE1
Conditions: Healthy
Sponsor: Pfizer

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1
Title P a ge
A P H A S E 1, R A N D O MI Z E D, O P E N -L A B E L, 2 -P A R T C R O S S O V E R S T U D Y T O 
A S S E S S T H E R E L A TI V E BI O A V AI L A BI LI T Y O F SI S U N A T O VI R F O L L O WI N G 
SI N G L E O R A L D O S E O F DI F F E R E N T F O R M U L A TI O N S U N D E R F E D A N D 
F A S T E D C O N DI TI O N S I N H E A L T H Y A D U L T P AR 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 C T N u m ber:
2 0 2 3 - 5 0 5 2 2 8- 7 9- 0 0
Cli nic al Tri als. g o v I D:  
N C T 0 5 9 9 4 9 6 3
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 3
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 Lear n H o w Differe nt Ma n ufact ure d Pr o d ucts of t he St u d y  Me dici ne Calle d 
Sis u nat o vir are Ta ke n U p I nt o t he Bl o o d W he n Ta ke n o n a n E m pt y St o mac h or W he n 
Ta ke n Wit h a Meal
i n Healt h y  A d ults
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 o f 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
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
0 9 N o ve m ber 2 0 2 3
Ori gi nal pr ot oc ol
0 7 J u ne 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 (0 9 N o v e m ber 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 a d d 
Part 2 f or t he e val uati o n of a l o w-fat meal o n sis u nat o vir e x p os ure wit h t he W G T 
f or m ulati o n.
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
S u bst a nti al M o dific ati o n(s)
U p date d pr ot oc ol title t o 
“ 2-P A R T C R O S S O V E R 
S T U D Y”
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of
W G T f or m ulati o n
Title pa ge a n d Secti o n 1. 1 
S y n o psis
Di vi de d sec o n dar y  
o bjecti ve/e n d p oi nt i nt o 
hi g h -fat meal a n d l o w-fat 
meal
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of 
W G T
f or m ulati o n
Secti o n 1. 1 S y n o psis a n d 
Secti o n 3 O bjecti ves a n d 
E n d p oi nts
Clarifie d t he “fe d c o n diti o n”
i n t he ori gi nal st u dy desi g n 
(ie, Part 1) as “wit h a 
hi g h -fat meal”
Clarifie d per t he ne w st u d y  
desi g n
Secti o n 1. 1 S y n o psis, 
Secti o n 3 O bjecti ves a n d 
E n d p oi nts, Secti o n 4. 1 
O verall Desi g n, Secti o n 4. 2 
Scie ntific Rati o nale f or 
St u d y  Desi g n, Secti o n 5. 3. 2 
Meals a n d Dietar y  
Restricti o ns, Secti o n 6. 1 
St u d y  Inter ve nti o n(s) 
A d mi nistere d, a n d 
Secti o n 9. 3. 3 Sec o n da r y 
E n d p oi nt(s) A nal ys is
U p date d o verall st u d y  
desi g n b y  r e-defi ni n g t he 
ori gi nal st u d y desi g n as 
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of 
W G T f or m ulati o n
Secti o n 1. 1 S y n o psis a n d 
Secti o n 4. 1 O verall Desi g n
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
Part 1 a n d a d di n g a ne w 
Part 2, a n d a d de d 
Treat me nt D – sis u nat o vir 
 m g W G T a d mi nistere d 
wit h a l o w-fat meal i n Part 2
U p date d t he t otal n u m ber of 
partici pa nts t o be e nr olle d i n 
t his st u d y t o “ bet wee n 1 2 
a n d 2 4”, i ncl u di n g 
a p pr o xi matel y 
1 2 partici pa nts i n Part 1 a n d
a p pr o xi matel y 
1 2 partici pa nts i n Part 2
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of 
W G T f or m ulati o n
S ecti o n 1. 1 S yn o psis
A d de d sc he d ule of 
assess me nts a n d P K 
sa m pli n g sc he d ule f or Part 2
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of 
W G T f or m ulati o n
Secti o n 1. 3 S c he d ule of 
Acti vities
A d de d t he st u d y ar ms a n d 
d urati o n i nf or mati o n f or 
Part 2
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of 
W G T f or m ulati o n
Secti o n 1. 1 S y n o psis a n d 
Secti o n 4. 1 O verall Desi g n
U p date d t he stati stical 
met h o ds f or t he hi g h -fat 
f o o d effect e val uati o n i n 
Part 1 a n d l o w-fat f o o d 
effect e val u ati o n i n Part 2
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of 
W G T f or m ulati o n
S ecti o n 1. 1 S yn o psis a n d 
Secti o n 9. 3. 3. 2 Ot her 
Sec o n dar y  E n d p oi nts 
A nal y ses
C orrecte d t he f oll o w- u p 
peri o d i nter prete d as St u d y  
D a y  t o “ D3 5- 4 3” f or Part 1
C orrecti o n i n ali g n me nt wit h 
t he f oll o w-u p peri o d defi ne d 
i n t his pr ot oc ol (ie, 
f oll o w- u p will occ ur 2 8 t o 
3 5 da y s after last d ose)
Secti o n 1. 3 Sc he d ule of 
Acti vities Ta ble 1
U p date d t he rati o nale f or 
t his st u d y t o reflect t he 
e val uati o ns f or hi g h- a n d 
l o w-fat f o o d effects
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of 
W G T f or m ulati o n
Secti o n 1. 1 S y n o psis a n d 
Secti o n 2. 1 St u d y  Rati o nale
U p date d t he scie ntific 
rati o nale f or st u dy desi g n 
base d o n t he preli mi nar y  P K 
data fr o m Part 1
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of 
W G T f or m ulati o n
Secti o n 4. 2 Scie ntific 
Rati o nale f or St u d y  Desi g n
U p date d t he defi niti o ns f or 
e n d of st u d y a n d 
a partici pa nt c o m pleti n g t he 
st u d y
T o ali g n wit h t he u p date d 
st u d y desi g n
Secti o n 4. 4 E n d of St u d y 
Defi niti o n
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
U p date d meals a n d dietar y  
restricti o ns t o reflect t he 
restricti o ns f or hi g h- a n d 
l o w-fat meals
T o ali g n wit h t he u p date d 
st u d y desi g n
Secti o n 5. 3. 2 Meals a n d 
Dietar y  Restricti o ns
A d de d a d mi nistrati o n details 
f or Part 2
E val uati o n of effect of a 
l o w-fat meal o n e x p os ure of 
W G T f or m ulati o n
Secti o n 6. 1. 1. 2 Part 2
U p date d t otal bl o o d 
sa m pli n g v ol u me
A d diti o nal Part 2
Secti o n 8. 1 A d mi nistrati ve 
a n d Baseli ne Pr oce d ures
Clarifie d t hat partici pa nts 
w h o ha ve c o m plete d Part 1
are eli gi ble t o partici pate i n 
Part 2 .
A d diti o nal Part 2
S ecti o n 1. 1 S yn o psis, 
Secti o n 4. 1 O verall Desi g n, 
a n d Secti o n 4. 2 Scie ntific 
Rati o nale f or St u d y  Desi g n.
N o n -s u bst a nti al M odific ati o n(s)
U p date d Cli nical Trials. g o v 
I D
U p date per a vai la ble 
i nf or mati o n
Title pa ge a n d Secti o n 1. 1 
S y n o psis
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5
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 4
2. 1. St u d y  Rati o nale.......................................................................................................2 4
2. 2. Bac k gr o u n d .............................................................................................................2 4
2. 2. 1. N o ncli nical P har mac ol o g y ..........................................................................2 5
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 6
2. 3. Be nefit/ Ris k Assess me nt................................ .........................................................2 9
2. 3. 1. Ris k Assess me nt......................................................................................... 3 0
2. 3. 2. Be nefit Assess me nt .....................................................................................3 1
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................3 1
3. O BJ E C TI V E S A N D E N D P OI N T S .....................................................................................3 1
4. S T U D Y D E SI G N .................................................................................................................3 2
4. 1. O verall Desi g n .........................................................................................................3 2
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n.....................................................................3 3
4. 2. 1. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts .........................................3 4
4. 3. J ustificati o n f or D ose ..............................................................................................3 4
4. 4. E n d of St u d y  Defi niti o n ..........................................................................................3 4
5. S T U D Y P O P U L A T I ON................................ ......................................................................3 4
5. 1. I ncl usi o n Criteria................................ .....................................................................3 5
5. 2. E xcl usi o n Criteria ....................................................................................................3 5
5. 3. L ifest yle C o nsi derati o ns..........................................................................................3 7
5. 3. 1. C o ntrace pti o n ..............................................................................................3 7
5. 3. 2. Meals a n d Dietar y  Restricti o ns...................................................................3 8
5. 3. 3. Caffei ne, Alc o h ol, a n d T o bacc o .................................................................3 9
5. 3. 4. Acti vit y .......................................................................................................4 0
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6
5. 4. Scree n Fail ures ........................................................................................................4 0
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 0
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................4 0
6. 1. 1. A d mi nistrati o n ............................................................................................4 2
6. 1. 1. 1. Part 1 ................................ .........................................................4 2
6. 1. 1. 2. Part 2 ................................ .........................................................4 2
6. 2. Pre parati o n, Ha n dli n g, St ora ge, a n d Acc o u nta bilit y ...............................................4 3
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ........................................................................4 4
6. 3. Assi g n me nt t o St u d y I nter ve nti o n ...........................................................................4 4
6. 4. Bli n di n g................................ ...................................................................................4 4
6. 5. St u d y  Inter ve nti o n C o m plia nce ...............................................................................4 4
6. 6. D ose M o dificati o n ...................................................................................................4 5
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 5
6. 8. Treat me nt of O ver d ose................................ ............................................................4 5
6. 9. Pri or a n d C o nc o mita nt T hera p y................................ ..............................................4 5
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 ...........................................................................4 6
7. 1. Disc o nt i n uati o n of St u d y Inter ve nti o n ....................................................................4 6
7. 1. 1. P ote ntial Cases of Ac ute Ki d ne y  Inj ur y .....................................................4 6
7. 1. 2. E C G C ha n ges ..............................................................................................4 7
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 .......................................4 8
7. 2. 1. Wit h dra wal of C o nse nt ...............................................................................4 8
7. 3. L ost t o F oll o w -U p ...................................................................................................4 9
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................................ ...............................4 9
8. 1. A d mi nistrati ve a n d Baseli ne Pr oce d ures .................................................................4 9
8. 1. 1. Baseli ne Pr oce d ures ....................................................................................5 0
8. 2. Efficac y  Assess me nts ..............................................................................................5 0
8. 3. Safet y Assess me nts .................................................................................................5 0
8. 3. 1. P h y sical E xa mi nati o ns ................................................................................5 0
8. 3. 2. Vital Si g ns ..................................................................................................5 1
8. 3. 2. 1. B l o o d Press ure a n d P ulse Rate..................................................5 1
8. 3. 3. Electr ocar di o gra ms..................................................................................... 5 1
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7
8. 3. 4. Cli nical Safet y  La b orat or y Assess me nts....................................................5 2
8. 3. 5. Pre g na nc y  Testi n g ......................................................................................5 3
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 3
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 3
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ...............................................5 4
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 4
8. 4. 2. Met h o d of Detecti n g A Es a n d S A Es ..........................................................5 5
8. 4. 3. F oll o w -U p of A Es a n d S A Es ......................................................................5 5
8. 4. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................5 5
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 .....................................................5 5
8. 4. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................5 6
8. 4. 5. 2. E x p os ure D uri n g Breastfee di n g ................................................5 7
8. 4. 5. 3. Occ u pati o nal E x p os ure .............................................................5 8
8. 4. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................5 8
8. 4. 7. Dis ease-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 ..............................................................................5 8
8. 4. 8. A d verse E ve nts of S pecial I nterest............................................................. 5 8
8. 4. 8. 1. Lac k of Efficac y ........................................................................5 8
8. 4. 9. Me dical De vice Deficie ncies ......................................................................5 8
8. 4. 1 0. Me dicati o n Err ors .....................................................................................5 8
8. 5. P har mac o ki netics ....................................................................................................6 0
8. 6. Ge netics ...................................................................................................................6 0
8. 6. 1. S pecifie d Ge netics ......................................................................................6 0
8. 6. 2. Retai ne d Researc h Sa m ples f or Ge netics................................................... 6 0
8. 7. Bi o mar kers ..............................................................................................................6 0
8. 8. I mm u n o ge nicit y Assess me nts .................................................................................6 1
8. 9. Healt h Ec o n o mics ...................................................................................................6 1
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................ 6 1
9. 1. Statistical H y p ot hesis ..............................................................................................6 1
9. 2. A nal y sis Sets ...........................................................................................................6 1
9. 3. Statistical A nal y ses .................................................................................................6 2
9. 3. 1. Ge neral C o nsi derati o ns ...............................................................................6 2
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8
9. 3. 1. 1. Deri vati o n of P har mac o ki netic Para meters ...............................6 2
9. 3. 2. Pri mar y  E n d p oi nt(s) A nalys is.....................................................................6 3
9. 3. 3. Sec o n dar y  E n d p oi nt(s) A nalys is.................................................................6 3
9. 3. 3. 1. Safet y A nal ys es .........................................................................6 3
9. 3. 3. 2. Ot her Sec o n dar y E n d p oi nts A nal y ses .......................................6 4
9. 3. 4. Tertiar y / E x pl orat or y E n d p oi nt(s) A nalys is ................................................6 4
9. 3. 5. Ot her A nal ys es ............................................................................................6 4
9. 4. I nteri m A nal ys es .....................................................................................................6 5
9. 5. Sa m ple Size Deter mi nati o n................................ .....................................................6 5
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................................ ..........................................................................6 6
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...............6 6
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................6 6
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 .........................................................................6 6
1 0. 1. 2. Fi na ncial Discl o s ure .................................................................................6 7
1 0. 1. 3. I nf or me d C o nse nt Pr ocess ........................................................................6 7
1 0. 1. 4. Data Pr otecti o n .........................................................................................6 8
1 0. 1 . 5. C o m mittees Str uct ure ...............................................................................6 8
1 0. 1. 5. 1. Data M o nit ori n g C o m mittee ...................................................6 8
1 0. 1. 6. Disse mi nati o n of Cli nical St u d y  Data ......................................................6 8
1 0. 1. 7. Data Q ualit y Ass ura nce ............................................................................6 9
1 0. 1. 8. S o urce D oc u me nts ....................................................................................7 1
1 0. 1. 9. Use of Me dical Rec or ds ............................................................................7 1
1 0. 1. 1 0. St u d y  a n d Site Start a n d Cl os ure ............................................................7 2
1 0. 1. 1 1. P u blicati o n P olic y ...................................................................................7 2
1 0. 1. 1 2. S p o ns or’s Me dicall y  Q ualifie d I n di vi d ual..............................................7 3
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests.................................................................7 4
1 0. 3. A p pe n di x 3: A d ve rse 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 .....................................................................7 6
1 0. 3. 1. Defi niti o n of A E .......................................................................................7 6
1 0. 3. 2. Defi niti o n of a n S A E ................................................................................7 7
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9
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............................................................................7 8
1 0. 3. 4. Re p orti n g of S A Es.................................................................................... 8 2
1 0. 4. A p pe n di x 4: C o ntrace pti ve a n d Barrier G ui da nce ................................................8 3
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria.................................... 8 3
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria .................................8 3
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ............................................................8 4
1 0. 4. 4. C o ntrace pti o n Met h o ds .............................................................................8 5
1 0. 5. A p pe n di x 5: 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 .......8 7
1 0. 6. A p pe n di x 6: Ki d ne y  Safet y: M o nit ori n g G ui deli nes ............................................8 9
1 0. 6. 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 ..............................................................................8 9
1 0. 6. 2. A ge -S pecific Ki d ne y  F u ncti o n Calc ulati o n Rec o m men dati o ns............... 8 9
1 0. 6. 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........................................................................................... 8 9
1 0. 6. 3. Ki d ne y  F u ncti o n Calc ulati o n T o ols..........................................................8 9
1 0. 6. 4. A d verse E ve nt Gra di n g f or Ki d ne y  Safety La b o rat or y 
A b n or malities ...................................................................................................9 0
1 0. 7. A p pe n di x 7: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n ...................................9 1
1 0. 8. A p pe n di x 8: 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 .......9 3
1 0. 9. A p pe n di x 9: A b bre viati o ns ................................ ...................................................9 6
1 1. R E F E R E N C E S ................................................................................................................1 0 0
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
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 ( Part 1)....................................................1 9
Ta ble 2.
St u d y  Sc he d ule of Assess me nt ( Part 2)....................................................2 1
Ta ble 3.
Detaile d P K Sa m pli n g Sc he d ule ( Part 1).................................................. 2 3
Ta ble 4.
Detaile d P K Sa m pli n g Sc he d ule ( Part 2) ..................................................2 3
Ta ble 5.
C o m plete d Sis u nat o vir Cli nical St u dies ..................................................2 7
Ta ble 6.
Part 1 Treat me nt Se q ue nce .......................................................................3 2
Ta ble 7.
Part 2 Treat me nt Se q ue nce .......................................................................3 3
Ta ble 8.
Plas ma P K Para meters ..............................................................................6 2
Ta ble 9.
E x pecte d Wi dt hs of t he 9 0 % CI s ( wit h 8 0 % C o vera ge Pr o ba bilit y) 
f or Differe nt P ossi ble Relati ve Effect Esti mates at N = 1 2 ......................6 5
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
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, O pe n -La bel, 2- Part Cr oss o ver St u d y  t o Assess t he Relati ve 
Bi oa vaila bilit y of Sis u nat o vir F oll o wi n g Si n gle Oral D ose of Differe nt F or m ulati o ns U n der
Fe d a n d Faste d C o n diti o ns i n Healt h y  A d ult Partici pa nts 
B rief Title:
A St u d y  t o Lear n H o w Differe nt Ma n ufact ure d Pr o d ucts of t he St u d y  Me dici ne Calle d 
Sis u nat o vir are Ta ke n U p I nt o t he Bl o o d W he n Ta ke n o n a n E m pt y St o mac h or W he n Ta ke n 
Wit h a Meal
i n Healt h y  A d ults
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 C T N u m ber:
2 0 2 3 -5 0 5 2 2 8 -7 9 -0 0
Cli nic al Tri als. g o v I D:  
N C T 0 5 9 9 4 9 6 3
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N ot A p plica ble
Pr ot oc ol N u m ber:
C 5 2 4 1 0 1 3
P h ase:
1
R ati o n ale :
T his st u d y  is desi g ne d t o assess safety , t olera bilit y, p har mac o ki netics ( P K), a n d f o o d effect
of a si n gle oral d ose of 2 differe nt f or m ulati o ns of sis u nat o vir. T he oral P K of a ne w Wet 
Gra n ulati o n Ta blet (W G T) f or m ulati o n p ote ntiall y t o be use d i n f ut ure cli nical st u dies will be 
c o m pare d wit h t hat of c urre nt P o w der i n Ca ps ule ( PI C) use d i n c o m plete d a n d ot her o n g oi n g 
cli nical st u dies. A d diti o nall y , t he hi g h - a n d l o w-fat f o o d effects o n t he oral P K of t he ne w 
W G T f or m ulati o n will be e val uate d.
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 deter mi ne t he relati ve bi oavaila bilit y of sis u nat o vir 
f oll o wi n g a si n gle oral d ose of  
 m g as PI C vs W G T i n a 
faste d state

A U C last, A U C i nf (if data per mit* ), a n d C ma x of 
PI C vs W G T
Sec o n d ar y: 
Sec o n d ar y:

T o deter mi ne t he effect of a hi g h -fat me al o n t he relati ve 
bi o a vaila bilit y of sis u nat o vir f oll o wi n g a si n gle oral d ose of 
m g as W G T

A U C last, A U Ci nf (if data per mit* ), a n d C ma x of 
W G T u n der faste d vs wit h a hi g h -fat me al
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 2
O bjecti ves
E n d p oi nts

T o deter mi ne t he effect of a l o w- fat meal o n t he relati ve 
bi o a vaila bilit y of sis u nat o vir f oll o wi n g a si n gle oral d ose of 
m g as W G T

A U C last, A U Ci nf (if data per mit* ), a n d Cma x of 
W G T u n der faste d vs wit h a l o w -fat meal

T o c haracterize t he safet y a n d t olera bilit y f oll o wi n g a si n gle 
oral d ose of  
 m g of sis u nat o vir as PI C or W G T i n a faste d 
state, or as W G T
i n a fe d state

Assess me nt of T E A Es, cli nical la b orat or y 
a b n or malities, vital si g ns, a n d 1 2 -lea d E C Gs
* S h o ul d it be dee me d t hat t o o fe w A U C i nf esti mates (e g, less t ha n 1 0 f or a si n gle d ose ) are o btai ne d fr o m t he e val ua ble 
partici pa nts, A U C last ma y be selecte d as t he pri mar y/sec o n dar y e n d p oi nt f or C S R re p orti n g. 
A b bre viati o ns: A U C i nf = area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o i nfi nit y; A U Clast = area u n der t he 
c o nce ntrati o n -ti me c ur ve fr o m 0 t o ti me of last meas ura ble c o nce ntrati o n; Cma x = ma xi m u m o bser ve d c o nce ntrati o n; C S R 
= cli nical st u d y re p ort; E C G = electr ocar di o gra m; T E A E = treat me nt -e mer ge nt a d verse e ve nt.
O ver all Desi g n:
T his is a P hase 1, ra n d o mize d, o pe n -la bel, 2- part cr oss o ver st u d y t o e val uate t he P K, f o o d 
effect, safet y, a n d t olera bilit y of sis u nat o vir 
 m g si n gle d ose a d mi nistere d as PIC or W G T 
u n der faste d c o n diti o n s, or as W G T wit h f o o d.
Part 1
Partici pa nts will be a d mitte d t o t he cli nical researc h u nit ( C R U ) o n Da y  -1 t o u n der g o 
baseli ne pr oce d ures. O ver t he first 2 peri o ds, all partici pa nts are pla n ne d t o recei ve 1 d ose of 
( A) sis u nat o vir 
 m g as PIC a n d 1 d ose of ( B) sis u nat o vir 
 m g as W G T i n a faste d 
state. All partici pa nts i n Peri o d 3 will recei ve 1 d ose of ( C) sis u nat o vir 
 m g as W G T
wit h 
a hi g h-fat meal. T here is an at least 7 2- h o ur was h o ut peri o d bet wee n t he d ose of 2 a djace nt 
peri o ds . 
P art 1 St u d y Desi g n
Peri o d 1
Peri o d 2
Peri o d 3
Se q ue nce 1 ( N = 6)
A
B
C
Se q ue nce 2 ( N = 6)
B
A
C
All st u d y i nter ve nti o ns will be a d mi nistere d as a si n gle d ose of 
-m g sis u nat o vir as PI C or W G T.
A = PI C u n der faste d c o n dit io n; B = W G T u n der faste d c o n diti o n; C = W G T w it h a hi g h-fat meal.
Part 1 c o nsists of a n i nitial scree ni n g peri o d of u p t o 2 8 da y s ( w hile all o wi n g f or t he ret ur n 
a n d re vie w of all res ults, i ncl u di n g la b orat or y  tests), a 1 0-d a y  i n patie nt sta y at t he C R U 
w hic h i ncl u des 3 peri o ds, a n d a f oll o w -u p c o ntact t hat will occ ur 2 8 -3 5 da y s after t he last 
a d mi nistrati o n of sis u nat o vir. 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 or p h o ne call will ra n ge fr o m a p pr o xi matel y  
6 wee ks ( mi ni m u m) t o a p pr o xi matel y  1 0 wee ks ( ma xi m u m).
A p pr o xi matel y  1 2 partici pa nts will be ra n d o mize d i nt o 2 se q ue nces wit h a p pr o xi matel y 
6 partici pa nts i n eac h. F or eac h se q ue nce, partici pa nts will recei ve st u d y i nter ve nti o ns i n a 
pre -s pecifie d ma n ner as liste d i n t he ta ble f or Part 1 St u d y  Desi g n. Partici pa nts w h o 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 3
disc o nti n ue fr o m t he st u d y f or n o n -safety reas o ns ma y be re place d at t he s p o ns or’s discreti o n 
i n c olla b orati o n wit h t he i n vesti gat or.
Part 2
Partici pa nts will be a d mitte d t o t he C R U o n Da y  -1 t o u n der g o baseli ne pr oce d ures. A ll 
partici pa nts are pla n ne d t o recei ve 1 d ose of ( B ) sis u nat o vir  
 m g as W G T i n a faste d state
a n d 1 d ose of ( D) sis u nat o vir  
 m g as W G T wit h a l o w -fat meal. T here is an at least
7 2- h o ur was h o ut peri o d bet wee n Peri o d 1 a n d Peri o d 2. Partici pa nts w h o ha ve partici pate d i n
Part 1 are eli gi ble t o partici pate i n Part 2.
P art 2 St u d y Desi g n 
Peri o d 1
Peri o d 2
Se q ue nce 1 ( N = 6)
B
D
Se q ue nce 2 ( N = 6)
D
B
All st u d y i nter ve nti o ns will be a d mi nistere d as a si n gle d ose of 
-m g sis u nat o vir as W G T.
B = W G T u n der faste d c o n diti o n; D = W G T wit h a l o w-fat meal.
Part 2 c o nsists of a n i nitial scree ni n g peri o d of u p t o 2 8 da y s, a 7- d a y  i n patie nt sta y at t he 
C R U w hic h i ncl u des 2 peri o ds, a n d a f oll o w -u p c o ntact t hat will occ ur 2 8 -3 5 da y s after t he 
last a d mi nistrati o n of sis u nat o vir. 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 or p h o ne call will ra n ge fr o m 
a p pr o xi matel y 6 wee ks ( mi ni m u m) t o a p pr o xi matel y  1 0 wee ks ( ma xi m u m).
A p pr o xi matel y  1 2 partici pa nts will be ra n d o mize d i nt o 2 se q ue nces wit h a p pr o xi matel y
6 partici pa nts i n eac h. F or eac h se q ue nce, partici pa nts will recei ve st u d y i nter ve nti o ns i n a 
pre -s pecifie d ma n ner as liste d i n t he ta ble f or Part 2 St u d y  Desi g n. Partici pa nts w h o 
disc o nti n ue fr o m t he st u d y f or n o n-safety reas o ns ma y be re place d at t he s p o ns or’s discreti o n 
i n c olla b orati o n wit h t he i n vesti gat or.
N u m ber of P artici p a nts:
A p pr o xi matel y  1 2 partici pa nts will be e nr olle d i n Part 1 a n d a p pr o xi matel y 1 2 partici pa nts 
will be e nr olle d i n Part 2 . S o me partici pa nts ma y  partici pate i n b ot h Parts 1 a n d 2 , t heref ore 
t he t otal n u m ber of partici pa nts i n t his st u d y will be bet wee n a p pr o xi matel y 1 2 a n d 2 4 .
N ote: “E nr olle d ” mea ns a partici pa nt ’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/assi g n me nt t o st u d y 
i nter ve nti o n.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 4
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 
Partici pa nts m ust meet t he f oll o wi n g ke 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: Male a n d fe male partici pa nts a ge d 1 8 y ears or ol der ( or t he mi ni m u m a ge of 
c o nse nt i n acc or da nce wit h l ocal re g ulati o ns) at scree ni n g 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 ys ical e xa mi nati o n, 
la b orat or y tests, a n d car diac e val uati o n .
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 ntestinal, car di o vasc ular, he patic, ps yc 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).
2.
A n y  me dical or psyc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) 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 t hat ma y 
i ncrease t he ris k of st u dy 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 
p artici 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:
3.
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 m o derate/str o n g c yt oc hr o me P 4 5 0 3 A (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. 
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
4.
Pre vi o us a d mi nis trati 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:
5.
A p ositi v e uri ne dr u g test, c o nfir me d b y a re peat e d test, if dee me d necessar y. 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 5
6.
F or partici pa nts < 6 0 ye ars: scree ni n g s u pi ne bl o o d press ure ( B P ) ≥1 4 0 m m H g 
(s yst 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. F or 
partici pa nts ≥6 0 y ears ol d, a scree ni n g s u pi ne B P of ≥1 5 0/ 9 0 m m H g ma y  be use d. If 
s yst olic B P is ≥ 1 4 0 or 1 5 0 m m H g ( base d o n a ge) or diast olic ≥9 0 m m H g, 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 eli gi bilit y .
7.
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 c orrecte d usi n g 
Fri dericia’s f or m ula [ Q Tc F ] > 4 5 0 ms, c o m plete left b u n dle bra nc h bl oc k [L B B B ],
si g ns of a n ac ute or i n deter mi nate- a ge m y ocar 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 atri o ve ntric ular [ 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 
eli gi bilit 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.
8.
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 ni cal 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: esti mate d gl o mer ular filtrati o n rate ( eG F R )
< 6 0 m L / mi n/ 1. 7 3 m2 base d o n c hr o nic ki d ne y disease e pi de mi ol o g y (C K D -E PI )
e q uati o n; as partate a mi n otra nsferase ( A S T ) or ala ni ne a mi n otra nsferase ( A L T) le vel 
≥1. 0 5 × u p per li mit of n or mal ( U L N ); ga m ma -gl uta m y l tra nsferase (G G T ) >1. 0 5 × 
U L N; al kali ne p h os p hatase ( A L P) > 1. 0 5 × U L N; t otal bilir u bi n le vel ≥1. 0 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.
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 ra n ge fr o m a p pr o xi matel y  6 wee ks ( mi ni m u m) t o a p pr o xi matel y  
1 0 wee ks ( ma xi m u m) f or eac h of Part 1 a n d Part 2 .
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
Sis u nat o vir
Use
E x peri me ntal
I n vesti g ati o n al Me dici n al Pr o d uct (I M P) or N o n-I n vesti g ati o n al Me dici n al 
Pr o d uct ( NI M P) / A u xili ar y Me dici n al Pr o d uct ( A x M P)
I M P
D ose F or m ul ati o n
PI C or W G T
U nit D ose Stre n gt h(s)
 m g f or PI C or
 m g f or W G T
R o ute of A d mi nistr ati o n
Oral
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 6
P art 1 St u d y Ar m(s)
Ar m Title
Treat me nt A
Treat me nt B
Treat me nt C
Ar m 
Descri pti o n
Partici pa nts will recei ve a 
si n gle  
 m g d ose of 
sis u nat o vir PI C a d mi nistere d 
orall y as
sis u nat o vir 
-m g 
ca ps ules u n der a faste d 
c o n diti o n .
Partici pa nts will recei ve a si n gle 
 m g d ose of sis u nat o vir W G T 
a d mi nistere d orall y as 
sis u nat o vir  
-m g ta blets 
u n der a faste d c o n diti o n .
Partici pa nts will recei ve a 
si n gle  
 m g d ose of 
sis u nat o vir W G T a d mi nistere d 
orall y as sis u nat o vir 
-m g 
ta blets wit h a hi g h -fat meal .
P art 2 St u d y Ar m(s)
Ar m Title
Treat me nt B
Treat me nt D
Ar m 
Descri pti o n
Partici pa nts will recei ve a si n gle  
 m g d ose of 
sis u nat o vir W G T a d mi nistere d orall y as 
sis u nat o vir  
-m g ta blets u n der a faste d 
c o n diti o n .
Partici pa nts will recei ve a si n gle  
 m g d ose of 
sis u nat o vir W G T a d mi nistere d orall y as
sis u nat o vir  
-m g ta blets wit h a l o w-fat meal.
St atistic al Met h o ds :
A s ufficie nt n u m ber of partici pa nts will be scree ne d t o ac hie ve a p pr o xi matel y  1 2 partici pa nts 
ra n d o mize d t o st u d y i nter ve nti o n i n eac h of Part 1 a n d Part 2 . T he sa m ple size is e m piricall y 
selecte d a n d is n ot base d o n statistical p o wer calc ulati o n.
Part 1
T o c o m pare t he Treat me nts A ( PI C u n der faste d c o n diti o n) a n d B ( W G T
u n der faste d 
c o n diti o n), nat ural l o g tra nsf or me d A U C last, A U C i nf (if data per mit) a n d Cma x of sis u nat o vir 
will be a nal yz e d se paratel y usi n g a mi xe d effect m o del wit h se q ue nce ( A B or B A), peri o d 
a n d treat me nt i ncl u de d as fi xe d effects a n d partici pa nt neste d wit hi n se q ue nce as a ra n d o m 
effect. O nl y data fr o m t he first 2 st u d y peri o ds will be use d i n t he a nalys is. Treat me nt A is 
t he Refere nce treat me nt a n d Treat me nt B is t he Test treat me nt.
F or t he hi g h -fat f o o d effect e val uati o n, nat ural l o g tra nsf or me d A U C last, A U C i nf (if data 
per mit) a n d C ma x of sis u nat o vir will be a nal yz e d usi n g a mi xe d effect m o de l wit h se q ue nce, 
a n d treat me nt as fi xe d effects a n d partici pa nt wit hi n se q ue nce as a ra n d o m effect. O nl y data 
fr o m Treat me nt B (W G T
u n der faste d c o n diti o n s) a n d Treat me nt C ( W G T
wit h a hi g h -fat 
meal ) will be i ncl u de d i n t he m o del. Treat me nt B is t he Refere nce treat me nt, Treat me nt C is
t he Test treat me nt.
Part 2
F or t he l o w-fat f o o d effect e val uati o n, nat ural l o g tra nsf or me d A U C last, A U Ci nf (if data 
per mit) a n d C ma x of sis u nat o vir will be a nal yz e d usi n g a mi xe d effect m o del wit h se q ue nce, 
a n d treat me nt as fi xe d effects a n d partici pa nt wit hi n se q ue nce as a ra n d o m effect. D ata fr o m 
Treat me nt B ( W G T u n der faste d c o n diti o ns) a n d Treat me nt D ( W G T wit h l o w -fat meals) 
will be i ncl u de d i n t he m o del. Treat me nt B is t he Refere nce treat me nt, Treat me nt D is t he 
Tes t treat me nt.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( 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

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 7
Part 1 a n d Part 2
Esti mates of t he a dj uste d mea n differe nces ( Test -Refere nce) a n d c orres p o n di n g 9 0 % 
c o nfi de nce i nter vals (CI s) will be o btai ne d fr o m t he m o del. T he a dj uste d mea n differe nces 
a n d 9 0 % CIs f or t he differe nces will be e x p o ne ntiate d t o pr o vi de esti mates of t he rati o of 
a dj uste d ge o metric mea ns ( Test/ Refere nce) a n d 9 0 % CI s f or t he rati os. 
Et hic al C o nsi der ati o ns:
Sis u nat o vir is n ot e x pecte d t o pr o vi de a n y cli nical be nefit t o healt h y partici pa nts. T his st u d y 
is desi g ne d pri maril y t o ge nerate safet y, t olera bilit y, P K , a n d f o o d effect data f or f urt her 
cli nical de vel o p me nt.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 8
1. 2. Sc he m a
N ot a p plica ble.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 9
1. 3. S c he d ule of Acti v ities
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 hed ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d in 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 (P art 1 )
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 9 .
Scree n
A d missi o n
Peri o ds 1- 3
Peri o d 
3
F/ U
E T
N otes
D a ys Rel ati ve t o D a y 1 f or 
E ac h Peri o d
D 1
D 2
D 3
D 4

Scree ni n g ≤2 8 da ys bef ore t he first d ose. 

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d will occ ur 
2 8 t o 3 5 da ys after last d ose.
P art 1 St u d y D a y
D- 2 8 t o 
D- 2
D- 1
D 1 / 4/7 D 2 / 5/ 8 D 3 / 6/ 9
D 1 0
D 3 5- 4 3
I nf or me d c o nse nt
X

I nf or me d c o nse nt m ust 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. 3 f or a d diti o nal i nf or mati o n.
C R U c o nfi ne me nt
X
 
 

X

Partici pa nts will be a d mitte d t o t he C R U o n Da y -1.
I ncl usi o n/e xcl usi o n criteria
X  
X
Me dical/ me dicati o n hist or y
X  
X

Pr oce d ure t o be c o m plete d pri or t o d osi n g i n Peri o d 1 .
P h ysical e xa m
X  
X
X

P E  at Scree ni n g or A d missi o n o nl y. A brief P E at ot her 
ti mes ma y be perf or me d 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.
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.

S afet y la b o n Da y -1 will ser ve as pre- d ose safet y la b f or
Peri o d 1, s o n o safet y la b o n P eri o d 1 D a y 1. Safe y la b will 
be c ollecte d pri or t o d osi n g o n Da y 1 of P eri o ds 2 a n d 3 .

I ncl u des he mat ol o g y, c he mistr y, a n d uri nal ysis , w hic h are 
liste d i n A p pe n di x 2 .
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

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.

See Secti o n 8. 3. 5 .
C o ntrace pti o n c hec k 
X
X
X
X
X
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 0
T a ble 1 .
St u d y Sc he d ule of Assess me nt (P art 1 )
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 9 .
Scree n
A d missi o n
Peri o ds 1- 3
Peri o d 
3
F/ U
E T
N otes
D a ys Rel ati ve t o D a y 1 f or 
E ac h Peri o d
D 1
D 2
D 3
D 4

Scree ni n g ≤2 8 da ys bef ore t he first d ose. 

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d will occ ur 
2 8 t o 3 5 da ys after last d ose.
P art 1 St u d y D a y
D- 2 8 t o 
D- 2
D- 1
D 1 / 4/7 D 2 / 5/ 8 D 3 / 6/ 9
D 1 0
D 3 5- 4 3
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
Si n gle 1 2 -Lea d E C G
X
X
X
X
B P a n d p ulse rate 
X
X
X
X

Da y 1 of eac h P eri o d pri or t o d ose a n d o n disc har ge da y. 
HI V, H Bs A g, H Bs A b, H Bc A b,
H C V A b 
X
St u d y i nter ve nti o n 
a d mi nistrati o n
X

Peri o d 1 a n d Peri o d 2 are d ose d i n a faste d state .

Peri o d 3 is d ose d i n a fe d state.
P K bl o o d sa m pli n g
X  
X  
X  
X
X

Detaile d P K sc he d ule i n Ta ble 3 .
C R U disc har ge 
X

Partici pa nts will be disc har ge d fr o m t he u nit o n Da y 4 of 
Peri o d 3 (St u d y Da y 1 0 ).
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. 4. 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 1
T a ble 2 .
St u d y Sc he d ule of Assess me nt ( P art 2 )
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 9 .
Scree n
A d missi o n
Peri o ds 1 - 2
Peri o d 2
F/ U
E T
N otes
D a ys Rel ati ve t o D a y 1 f or 
E ac h Peri o d
D 1
D 2
D 3
D 4

Scree ni n g ≤2 8 da ys bef ore t he first d ose. 

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d 
will occ ur 2 8 t o 3 5 da ys after last d ose.
P art 2 St u d y D a y
D- 2 8 t o D -
2
D- 1
D 1/ 4
D 2/ 5
D 3/ 6
D 7
D 3 2- 3 9
I nf or me d c o nse nt
X

I nf or me d c o nse nt m ust 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. 3 f or a d diti o nal i nf or mati o n.
C R U c o nfi ne me nt
X
 
 

X

Partici pa nts will be a d mitte d t o t he C R U o n Da y -
1.
I ncl usi o n/e xcl usi o n criteria
X  
X
Me dical/ me dicati o n hist or y
X  
X

Pr oce d ure t o be c o m plete d pri or t o d osi n g i n 
Peri o d 1.   
P h ysical e xa m
X  
X
X

P E  at Scree ni n g or A d missi o n o nl y. A brief P E at 
ot her ti mes ma y be perf or me d 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.
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.

Safet y la b o n Da y -1 w ill ser ve as pre-d ose safet y 
la b f or Peri o d 1, s o n o safet y la b o n Peri o d 1 Da y 
1. Safe y la b will be c ollecte d pri or t o d osi n g o n 
Da y 1 of Peri o ds 2.

I ncl u des he mat ol o g y, c he mistr y, a n d uri nal ysis, 
w hic h are liste d i n A p pe n di x 2 .
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

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.

See Secti o n 8. 3. 5 .
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
Si n gle 1 2 -Lea d E C G
X
X
X
X
B P a n d p ulse rate 
X
X
X
X

Da y 1 of eac h Peri o d pri or t o d ose a n d o n 
disc har ge da y. 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 2
T a ble 2 .
St u d y Sc he d ule of Assess me nt ( P art 2 )
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 9 .
Scree n
A d missi o n
Peri o ds 1 - 2
Peri o d 2
F/ U
E T
N otes
D a ys Rel ati ve t o D a y 1 f or 
E ac h Peri o d
D 1
D 2
D 3
D 4

Scree ni n g ≤2 8 da ys bef ore t he first d ose. 

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d 
will occ ur 2 8 t o 3 5 da ys after last d ose.
P art 2 St u d y D a y
D- 2 8 t o D -
2
D- 1
D 1/ 4
D 2/ 5
D 3/ 6
D 7
D 3 2- 3 9
HI V, H Bs A g, H Bs A b, 
H Bc A b, H C V A b 
X
St u d y i nter ve nti o n 
a d mi nistrati o n
X
P K bl o o d sa m pli n g
X  
X  
X  
X
X

Detaile d P K sc he d ule i n Ta ble 4 .
C R U disc har ge 
X

Partici pa nts will be disc har ge d fr o m t he u nit o n 
Da y 4 of Peri o d 2 ( St u d y Da y 7 ). 
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. 4. 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 3
T a ble 3 .
Det aile d P K S a m pli n g Sc he d ule ( P art 1 )
Visit I de ntifier
Peri o ds 1 - 3
Peri o d 3
N otes
Peri o d D a y
1
2 
3 
4
H o urs After M or ni n g 
D ose
0
1
2
3
4
5
6
8
1 0
1 2 
2 4 
3 6 
4 8
7 2
H o ur 0 = pre d ose sa m ple c ollecti o n
St u d y i nter ve nti o n 
a d mi nistrati o n
X
P K bl o o d sa m pli n g 
X
X
X
X
X
X
X
X
X  
X  
X  
X  
X  
X 
Pre d ose sa m ple c ollecte d i n Peri o ds 2 a n d 3 are 7 2 h o urs p ost d ose P K sa m ple f or 
Peri o d s 1 a n d 2, res pecti vel y.
T a ble 4 .
Det aile d P K S a m pli n g Sc he d ule ( P art 2 )
Visit I de ntifier
Peri o ds 1 a n d 2
Peri o d 2
N otes
Peri o d D a y
1
2 
3 
4
H o urs After M or ni n g D ose
0
1
2
3
4
5
6
8
1 0
1 2
2 4
3 6
4 8
7 2
H o ur 0 = pre d ose sa m ple c ollecti o n
St u d y i nter ve nti o n a d mi nistrati o n
X
P K bl o o d sa m pli n g 
X
X
X
X
X
X
X
X
X  
X  
X  
X  
X  
X 
Pre d ose sa m ple c ollecte d i n Peri o d 2 are 7 2 h o urs p ost d ose P K sa m ple f or Peri o d 1.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 4
2. I N T R O D U C TI O N
Sis u nat o vir ( P F -0 7 9 2 3 5 6 8, f or merl y R V 5 2 1) is a n orall y a d mi nistere d 
 
 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 assess t he P K, safet y, a n d t olera bilit y of a si n gle oral d ose of 
2 differe nt f or m ulati o ns of sis u nat o vir w he n a d mi nistere d u n der fasti n g c o n diti o ns . T he oral 
P K of a ne w W G T
f or m ulati o n p ote ntiall y t o be use d i n f ut ure cli nical st u dies will be 
c o m pare d wit h t hat of P I C f or m ulati o n use d i n c o m plete d a n d o n g oi n g cli nical st u dies. 
A d diti o nall y , t he hi g h - a n d l o w-fat f o o d effects o n t he oral P K of t he ne w W G T
f or m ulati o n 
will be e val uate d.
2. 2. B ac k gr o u n d 
R S V is u bi q uit o us a n d 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 ] The cli nical 
m a nifestati o n of R S V i nfecti o n is t ypicall y mil d U R TI . H o we ver, i n i nfa nts, yo u n g c hil dre n, 
i m m u n oc o m pr o mise d a n d t he el derly, it ca n ca use se vere L R T I lea di n g t o h os pitalizati o n , 
I C U a d missi 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 li mite d treat me nt meas ures, pri maril y 
c o nsisti n g of s u p p orti ve care. T here are, as yet, o nl y  2 a p pr o ve d a nti virals. T he first, 
ri ba viri n, is a n ucle osi de a nal o g ue, b ut cli nical use is restricte d d ue t o its li mite d a nti viral 
p ote nc y , deli ver y r o ute, t o xicit y a n d terat o ge nic p ote ntial.[5 ] T he ot her is t he m o n ocl o nal 
a nti b o d y Sy na gis ( pali viz u ma b) w hic h i nteracts wit h F gl yc o pr otei n of t he R S V vir us a n d 
has bee n a p pr o ve d i n t he U S a n d E U .[6 ,7 ] Pali viz u ma b has bee n s h o w n t o pr o vi de pr otecti o n 
i n i nfa nts at ris k of se vere disease, b ut nee ds t o be gi ve n bef ore i nfecti o n a n d is a d mi nistere d 
m o nt hl y  t hr o u g h o ut t he wi nter seas o n.[7 ] It is a p pr o ve d f or use i n i nfa nts wit h a hist or y of 
pre mat urit y, he m o d y na m icall y si g nifica nt car diac disease or c hr o nic l u n g disease of 
pre mat urit y. Rece ntl y ( N o ve m ber 2 0 2 2), Nirse vi ma b, a m o n ocl o nal a nti b o d y  t o t he R S V F 
pr otei n t hat has a n e xte n de d half -life, was a p pr o ve d f or pre ve nti o n of R S V-L R TI  i n 
ne w b or ns a n d i nfa nts d uri n g t heir first R S V seas o n i n t he E U.[ 8 ] T here re mai ns, h o we ver, a n 
o n g oi n g u n met cli nical nee d f or a n effecti ve t hera p y  f or R S V disease i n c hil dre n, a n d a 
n u m ber of ne w treat me nts are i n de vel o p me nt.  
Sis u nat o vir ( P F -0 7 9 2 3 5 6 8) is a p ote nt i n hi bit or of
 
In t his wa y , 
F pr otei n i n hi biti o n ma y  re d uce b ot h viral re plicati o n a n d pat h ol o g y, re d uci n g t he se verity of 
R S V -L R TI . T h us, sis u nat o vir ma y pr o vi de cli nical be nefit t o pe diatric partici pa nts wit h R S V 
disease. 
T h e 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 . 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 5
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
 
 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 
 
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 unat o vir.
M ore details are prese nte d i n t he I B.
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 K 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 6 3 % 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 0. 3 8 1, 0. 5 2 4, 0. 2 6 6, 0. 4 8 0 a n d 0. 6 6 7 i n m o use, rat, d o g a n d g ui nea pi g, 
a n d h u ma n res pecti vel y. Re peat d osi n g st u d ies 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 4 4 m g/ k g t o 1 5 0 m g/ k g.
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 P 2 D 6. Res ults of a cli nical D DI st u d y ( C 5 4 2 1 0 0 4), usi n g 
 
Base d o n i n vitr o st u dies, t he P K of O C T 1 a n d M A T E 1 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 O C T 1 a n d M A T E 1 s u bstrates are 
pr o hi bite d i n t his st u d y  ( Secti o n 1 0. 8 ).
I n vitr o st u dies als o i n dicate t here is a ris k of i n hi biti o n of C Y Ps 1 A 2, 2 B 6, 2 C 9, 2 C 1 9, a n d 
3 A 4. T he D DI wit h C Y Ps 1 A 2, 2 B 6, 2 C 9, a n d 2 C 1 9 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).
I n vitr o st u dies i n dicate t hat sis u nat o vir is li kel y 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 cli nical D DI st u d y ( C 5 2 4 1 0 0 4) i n dicate d t hat
 
 
( Secti o n 1 0. 8 ).
M ore details are prese nte d i n t he I B.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI
C CI
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 6
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 y s) 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 verit y. 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 LP, 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 nly 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 , heart 
( de ge nerati o n/ necr osis of t he m yocar di u m) a n d l u n g ( vasc ular dege 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/ or 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. I n 
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 b y d ose-relate d 
decrease d b o d y 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 s yste 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 o wer 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 sys te mic mater nal e x p os ure ( A U C2 4) of 2 2 0 n g• h/ m L o n 
D a y  1 6 of gestati o n.
M ore details are prese nte d i n t he I B.
2. 2. 4. Cli nic al O ver vie w
T o date, 5 cli nical st u dies of sis u nat o vir ha ve bee n c o m plete d; of t hese, 4 st u dies w ere
c o n d ucte d i n healt h y a d ults. Ke y desi g n feat ures of t he c o m plete d cli nical st u dies i n healt h y 
a d ults are pr o vi de d i n Ta ble 5 , a n d s u m maries of t he ke y cli nical p har mac ol o g y, cli nical 
efficac y a n d cli nical safet y data fr o m t he c o m plete d st u dies are pr o vi de d i n t he secti o ns 
bel o w. 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 7
T a ble 5.
C o m plete d Sis u n at o vir Cli nic al 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/ N 
D ose, D osi n g Re gi me n
F o r m ul 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)
P hase 1, ra n d o mize 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
Part A ( S A D): 
2 4 Ca ucasia n a n d 
1 2 Ja pa nese
Part A: 
 
 m g 
DI C a
Part B ( M A D): 2 4
Part B:  
 
m g BI D ×
da ys 
f or a t otal of 
d oses
DI C a
Part C (f o o d effect 
a n d f or m ulati o n): 1 6
Part C:  
 m g  
DI C a
Li q ui d 
F or m ulati o n a
C 5 2 4 1 0 0 2
( pre vi o usl y 
R E V C 0 0 2)
P hase 2a, 
ra n d o mize 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 halle n ge vir us : 6 6
 m g or  
 m g 
BI D ×
da ys f or a t otal 
d oses
DI C 
C 5 2 4 1 0 0 4
( pre vi o usl y 
R E V C 0 0 4)
P hase 1, a da pti ve, 
part ra n d o mize 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
Mi daz ola m – 2 2
Itrac o naz ole – 2 0
Vera pa mil – 2 0
Rifa m pici n – 2 0  
As per petrat or:  
 m g 
BI D ×
 da ys
As victi m:  
 m g 
si n gle d ose bef ore a n d 
after i n d ucer/i n hi bit or 
treat me nt
DI C
C 5 2 4 1 0 0 5
( pre vi o usl y 
R E V C 0 0 5) 
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: 
9 
 m g, si n gle d oses 
i n t otal
1 × DI C (fe d) 
1 × PI C ( D P B )
dis perse d i n H 2O (fe d)
1 × PI C ( D P B )
dis perse d i n H 2O 
(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
PI 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 w ater , a n d 6 8 partici pa nts recei ve d DI C i n t he st u d y.
C o m plete d Pe diatric St u d y:

C 5 2 4 1 0 0 3 was a n e x -U S P hase 2 st u d y  t o c haracterize t he P K pr ofile a n d safet y t o 
sis u nat o vir i n R S V-i nfecte d h os pitalize d c hil dre n a ge d 1-3 6 m o nt hs (recr uit me nt 
c o m plete d Dece m ber 2 0 2 2; cli nical st u d y  re p ort i n pre parati o n). 5 1 pe diatric patie nts 
h os pitalize d d ue t o R S V -L R TI recei ve d eit her a si n gle d ose ( N = 1 9) or u p t o 5 da y s 
m ulti ple d ose ( q 1 2 h) ( N = 3 2) of sis u nat o vir or place b o. Partici pa nts 1 t o < 6 m o nt hs of 
a ge were a d mi nistere d sis u nat o vir u p t o 2. 5 m g/ k g q 1 2 h ( q 1 2 h) f or 5 da ys . 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( 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

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 8
Partici pa nts 6 t o 3 6 m o nt hs of a ge were a d mi nistere d sis u nat o vir u p t o 5. 0 m g/ k g 
q 1 2 h f or 5 da y s.
O n g oi n g St u dies:

C 5 2 4 1 0 0 6 is a n o n g oi n g P hase 1 st u d y  i n healt h y partici pa nts t o e val uate t he 
p har mac o ki netics, safet y a n d t olera bilit y of m ulti ple oral d oses of place b o,  
 m g, 
or  
 m g  
 sis u nat o vir w he n a d mi nistere d wit h f o o d or i n a fasti n g state a n d t he 
palata bilit y  of a si n gle d ose of sis u nat o vir.

C 5 2 4 1 0 0 8 is a n o n g oi n g P hase 1 st u d y  t o assess t he a bs or pti o n, meta b olis m, a n d 
eli mi nati o n ( A M E) a n d rec o ver y of [ 1 4 C]-sis u nat o vir. T he res ulti n g data will pr o vi de 
m ore detaile d i nf or mati o n t o better u n dersta n d t he A M E c haracte ristics of sis u nat o vir 
i n h u ma ns a n d t o g ui de f urt her de vel o p me nt of t he c o m p o u n d.
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 5 Dece m ber 2 0 2 2, 5 1 pe diatric patie nts 
h os pit alize d d ue t o R S V - L R TI ha ve recei ve d eit her a si n gle d ose ( N = 1 9) or m ulti ple BI D 
d oses of sis u nat o vir u p t o 5 da y s i n t he o n g oi n g C 5 2 4 1 0 0 3 st u d y ( N = 3 2).
I n a d ult st u dies, 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 dosi 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. T he m ost c o m m o nl y  
re p orte d treat me nt relate d T E A Es i n a d ults were i n t he GI dis or ders Sys te m Or ga n Class: 
na us ea, 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.
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. T here has bee n o ne seri o us A E of fe ver re p orte d i n t he pe diatric st u d y  
( C 5 2 4 1 0 0 3) i n a c hil d h os pitalize d wit h R S V i nfecti o n w h o recei ve d a si n gle d ose of 
sis u nat o vir. T his was c o nsi dere d seri o us beca use it pr ol o n ge d h os pitalizati o n, b ut t he S A E 
was re p orte d as n ot relate d t o I M P. I n St u d y C 5 2 4 1 0 0 2, t here was 1 S A E of s u b-ac ute 
m y ocar ditis re p orte d f or a partici pa nt o n place b o; t his was c o nsi dere d t o be ca usall y relate d 
t o t he c halle n ge vir us. 
I n a d ults, 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 
4- 6 h o urs wit h a half -life of 7-1 0 h o urs i n healt h y partici pa nts . Stea dy- state c o nce ntrati o ns 
were reac he d after a p pr o xi matel y 2 da ys of d osi n g a n d a 2-4 f ol d acc u m ulati o n of e x p os ure
f oll o wi n g a Q1 2 h d ose re gi me n. A U C a n d Cma x val ues i ncrease d i n a grea ter 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 i n 
C 5 2 4 1 0 0 1 a n d C 5 2 4 1 0 0 2 , 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 %- 1 2 7% f or C
ma x a n d 6 1. 7 %- 1 1 6 % f or A U C
1 2.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 9
T he effect of f o o d o n t he si n gle d ose P K was assesse d f or t he DI C a n d PI C ( D P B ) dis perse d 
i n water ( St u dies C 5 2 4 1 0 0 1 a n d C 5 2 4 1 0 0 5) . F or t he DI C, t he e xte nt of s yste 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 bility 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 19 0 % ( 9 0 % CI: 8 6. 2 % - 4 1 8 %) f or A U C i nf. It s h o ul d be note 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  
 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 PI C ( D P B ) dis perse d i n water t h e e xte nt o f s yste 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 4 0 3 a n d 
5 1 6 n g• h/ m L , res pecti vel y, wit h t he bet wee n-s u bject varia bility bei n g sli g htl y l o wer u n der 
faste d c o n diti o ns (% C V 6 9. 1 % c o m pare d wit h 7 9. 6 %). T he rati o of fe d/faste d was 7 4. 2 % 
( 9 0 % CI: 3 9. 0 % – 1 4 1 %) f or C
ma x a n d 7 7. 7 % ( 9 0 % CI : 4 4. 8 % – 1 3 5 %) f or A U C i nf. 
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 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 herm 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 
 m g a n d  
 m g sis u nat o vir d ose gr o u ps res pecti vely ( d ose d 
 f or 
da y s). Res ults f or t he A U C of t otal s ym 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 s y 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 x 
sc ore f or place b o,  
 m g sis u nat o vir a n d  
 m g sis u nat o vir, res pecti vely. 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  
 m g a n d  
 m g sis u nat o vir d ose gr o u ps, res p ecti vel y.
N o partici pa nt i n St u d y  C 5 2 4 1 0 0 1 ha d a Q Tc F i nter val c ha n ge fr o m baseli ne > 3 0 msec. 
F urt her m ore, 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 part ici pa nts 
( C 5 2 4 1 0 0 4).
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, w hic 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
Sis 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. T his st u d y 
is desi g ne d pri maril y t o ge nerate P K, f o o d effect, safety, a n d t olera bilit y data f or f urt her 
cli nical de vel o p 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. 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 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 0
are s u m marize d i n Secti o n 2. 2. 3 . 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 t he st u d y i nter ve nti o n.
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.
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: 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.
T o date, mil d tra nsie nt ele vati o ns of 
li ver e nz y mes ha ve bee n o bser ve d i n a 
fe w partici pa nts wit hi n cli nical st u dies.
Safet y m o nit ori n g i ncl u di n g 
la b orat or y (ie, tra nsa mi nases, 
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 feces 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 -da y d o g 
st u d y.
I n c o m plete d a d ult cli nical st u dies 
sis u nat o vir has bee n ass ociate d wit h 
mil d GI A Es.
Partici pa nts will be cl osel y 
e val uate d t o mo nit or f or GI A Es.
Car di o vasc ular effects
M y ocar dial de ge nerati o n a n d necr osis 
wa s 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.
T o date, P hase 1 st u dies i n healt h y 
partici pa nts a n d a P hase 1 b st u d y i n 
pe diatric partici pa nts has n ot 
s h o w n 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 
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. 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 1
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: Sis u n at o vir
tr o p o ni n i n C 5 2 4 1 0 0 1), E C Gs a n d vital 
si g ns relate d t o sis u nat o vir.
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
Sis u nat o vir is n ot e x pecte d t o pr o vi de a n y 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 deter mi ne t he relati ve bi oavaila bilit y of 
sis u nat o vir f oll o wi n g a si n gle oral d ose of  
 m g as 
P I C vs W G T
i n a faste d state 

A U C last, A U C i nf (if data per mit* ), a n d C ma x of PI C vs 
W G T
Sec o n d ar y: 
Sec o n d ar y: 

T o deter mi ne t he effect of a hi g h -fat meal o n t he
relati ve bi oavaila bilit y of sis u nat o vir f oll o wi n g a 
si n gle oral d ose of  
 m g as W G T

A U C last, A U Ci nf (if data per mit* ), a n d C ma x of W G T
u n der faste d vs wit h a hi g h -fat meal

T o deter mi ne t he effect of a l o w- fat meal o n t he 
relati ve bi oavaila bilit y of sis u nat o vir f oll o wi n g a 
si n gle oral d ose of  
 m g as W G T

A U C last, A U Ci nf (if data per mit* ), a n d Cma x of W G T 
u n der faste d vs wit h a l o w -fat meal

T o c haracterize t he safet y a n d t olera bilit y f oll o wi n g 
a si n gle oral d ose of  
 m g of sis u nat o vir as P I C or 
W G T
i n a faste d state, or as W G T
i n a fe d state

Assess me nt of T E A Es, cli nical la b orat or y 
a b n or malities, vital si g ns, a n d 1 2-lea d E C Gs
Terti ar y/ E x pl or at or y: 
Terti ar y/ E x pl or at or y: 

T o deter mi ne a d diti o nal P K para meters of 
sis u nat o vir f oll o wi n g a si n gle oral d ose of  
 m g as 
P I C or W G T
i n a faste d state, or as W G T
i n a fe d 
state

A d diti o nal plas ma P K para meters:  

C L/ F a n d V z/ F as data per mit

T ma x

t½ , as data per mit
* S h o ul d it be dee me d t hat t o o fe w A U C i nf esti mates (e g, less t ha n 1 0 f or a si n gle d ose ) are o btai ne d fr o m t he e val ua ble 
partici pa nts, A U C last ma y be selecte d as t he pri mar y/sec o n dar y e n d p oi nt f or C S R re p orti n g ( ot her wise A U C last will be a n 
e x pl orat or y e n d p oi nt).
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI
C CI
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 2
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 , ra n d o mize d, o pe n -la bel, 2-part cr oss o ver st u dy t o e val uate t he P K, f o o d 
effect, safet y, a n d t olera bilit y of sis u nat o vir
 m g si n gle d ose a d mi nistere d as P I C or W G T
u n der fast e d c o n diti o ns, or as W G T
wit h f o o d.
Part 1
Partici pa nts will be a d mitte d t o t he C R U o n Da y  -1 t o u n der g o baseli ne pr oce d ures. O ver t he 
first 2 peri o ds, all partici pa nts are pla n ne d t o recei ve 1 d ose of ( A) sis u nat o vir 
 m g as PI C 
a n d 1 d ose of ( B) sis u nat o vir  
 m g as W G T i n a faste d state. All partici pa nts i n Pe ri o d 3 
will recei ve 1 d ose of ( C) sis u nat o vir  
 m g as W G T wit h a hi g h -fat meal (Ta ble 6 ). T here 
is an at least 7 2- h o ur was h o ut peri o d bet wee n t he d ose of 2 a djace nt peri o ds.
Part 1 c o nsists of a n i nitial scree ni n g peri o d of u p t o 2 8 da y s ( w hile all o wi n g f or t he ret ur n 
a n d re vie w of all res ults, i ncl u di n g la b orat or y  tests), a 1 0-d a y  i n patie nt sta y at t he C R U 
w hic h i ncl u des 3 peri o ds, a n d a f oll o w -u p c o ntact t hat will occ ur 2 8 -3 5 da ys after t he last 
a d mi nistrati o n of sis u nat o vir. F or i n di vi d ual partici pa nts, t he t otal d urati o n of p artici pati o n 
fr o m t he scree ni n g visit t o t he f oll o w-u p visit or p h o ne call will ra n ge fr o m a p pr o xi matel y  
6 wee ks ( mi ni m u m) t o a p pr o xi matel y  1 0 wee ks ( ma xi m u m).
A p pr o xi matel y  1 2 partici pa nts will be ra n d o mize d i nt o 2 se q ue nces wit h a p pr o xi matel y 
6 partici pa nts i n eac h. F or eac h se q ue nce, partici pa nts will recei ve st u d y i nter ve nti o ns i n a 
pre -s pecifie d ma n ner as liste d i n Ta ble 6.
T a ble 6.
P art 1 Tre at me nt Se q ue nce
Peri o d 1
Peri o d 2
Peri o d 3
Se q ue nce 1 ( N = 6)
A
B
C
Se q ue nce 2 ( N = 6)
B
A
C
All st u d y i nter ve nti o ns will be a d mi nistere d as a si n gle d ose of sis u nat o vir 
 m g as PI C or W G T.
A = PI C u n der faste d c o n diti o n; B = W G T u n der faste d c o n diti o n; C = W G T wit h a hi g h -fat meal.
Partici pa nts w h o disc o nti n ue fr o m t he st u d y f or n o n -safety reas o ns ma y be re place d at t he 
s p o ns or’s discreti o n i n c olla b orati o n wit h t he i n vesti gat or.
Part 2
Partici pa nts will be a d mitte d t o t he C R U o n Da y  -1 t o u n der g o baseli ne pr oce d ures. All 
partici pa nts are pla n ne d t o recei ve 1 d ose of ( B) sis u nat o vir  
 m g as W G T i n a faste d state 
a n d 1 d ose of ( D) sis u nat o vir  
 m g as W G T wit h a l o w -fat meal. T here is an at least
7 2- h o ur was h o ut peri o d bet wee n t he d ose of t he 2 peri o ds. Partici pa nts w h o ha ve c o m plete d 
Part 1 are eli gi ble t o partici pate i n Part 2 .
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 3
T a ble 7.
P art 2 Tre at me nt Se q ue nce
Peri o d 1
Peri o d 2
Se q ue nce 1 ( N = 6)
B
D
Se q ue nce 2 ( N = 6)
D
B
All st u d y i nter ve nti o ns will be a d mi nistere d as a si n gle d ose of 
-m g sis u nat o vir as W G T.
B = W G T u n der faste d c o n diti o n; D = W G T w it h a l o w-fat meal.
Part 2 c o nsists of a n i nitial scree ni n g peri o d of u p t o 2 8 da y s, a 7-d a y  i n patie nt sta y at t he 
C R U w hic h i ncl u des 2 peri o ds, a n d a f oll o w- u p c o ntact t hat will occ ur 2 8 -3 5 da y s after t he 
last a d mi nistrati o n of sis u nat o vir. 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 or p h o ne call will ra n ge fr o m 
a p pr o xi matel y 6 wee ks ( mi ni m u m) t o a p pr o xi matel y  1 0 wee ks ( ma xi m u m).
A p pr o xi matel y  1 2 partici pa nts will be ra n d o mize d i nt o 2 se q ue nces wit h a p pr o xi matel y 
6 partici pa nts i n eac h. F or eac h se q ue nce, partici pa nts will recei ve st u d y i nter v e nti o ns i n a 
pre -s pecifie d ma n ner as liste d i n Ta ble 7. 
Partici pa nts w h o disc o nti n ue fr o m t he st u d y f or n o n -safety reas o ns ma y be re place d at t he 
s p o ns or’s discreti o n i n c olla b orati o n wit h t he i n vesti gat or.
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
T he pri mar y  p ur p ose of t his st u d y is t o assess t he relati ve bi oa vaila bility of sis u nat o vir 
m g a d mi nistere d u n der fast e d c o n diti o n as W G T
(a f or m ulati o n i nte n de d f or f ut ure 
cli nical st u dies) vs P I C (a f or m ulati o n use d i n C 5 2 4 1 0 0 3, C 5 2 4 1 0 0 5 a n d C 5 2 4 1 0 0 6). I n 
a d diti o n, f o o d effect will be e val uate d f or t he ne w W G T
f or m ulati o n. T heref ore, it was 
ori gi nall y desi g ne d t o be a 3- peri o d , cr oss -o ver st u d y  wit h 7 2 h o urs of was h o ut bet wee n t he 
d osi n g i n Peri o d s 1 a n d 2 or Peri o ds 2 a n d 3.
Base d o n preli mi nar y  P K data fr o m Part 1 , a f o o d effect was o bser ve d f or W G T a d mi nistere d 
wit h hi g h -fat meals c o m pare d t o W G T a d mi nistere d u n der a faste d state. I n or der t o ha ve a
t h or o u g h e val uati o n of t he effects of meals o n sis u nat o vir e x p os ure, Part 2 is a d de d t o assess 
t he oral P K of sis u nat o vir a d mi nistere d as W G T wit h l o w-fat meal s c o m pare d t o 
a d mi nistere d as W G T u n der a faste d state, i n a 2 -peri o d cr oss -o ver desi g n wit h at least 
7 2 h o urs of was h o ut bet wee n t he d osi n g i n Peri o ds 1 a n d 2 . Partici pa nts w h o ha ve 
partici pate d i n Part 1 ma y  als o partici pate i n Part 2 .
I n a d ults, t he half-life of sis u nat o vir is ~7- 1 0 h o urs i n healt h y  partici pa nts. T he effect of 
f or m ulati o n o n t he P K of sis u nat o vir has bee n i n vesti gate d i n C 5 2 4 1 0 0 1 (li q ui d vers us DI C 
f or m ulati o n) a n d C 5 2 4 1 0 0 5 (PI C [ D P B ] dis perse d i n water vs DI C f or m ulati o n). T here is n o 
i n dicati o n of a c ha n ge i n half-life acr oss f or m ulati o ns. T heref ore, c urre nt st u d y  desi g n wit h 
at least 7 2 h o urs of was h o ut is s u p p orte d b y t he t½ ( > 5× t ½ ) bet wee n d osi n g i n Perio ds 1 a n d 
2 or Peri o ds 2 a n d 3 , w hic h is c o nsi dere d a de q uate.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 4
T he effect of f o o d o n t he P K of a si n gle d ose of sis u nat o vir 
 m g was i n vesti gate d i n 
C 5 2 4 1 0 0 1 a n d C 5 2 4 1 0 0 5 , a n d a p pears t o be f or m ulati o n de pe n de nt (a d diti o nal details i n 
Secti o n 2. 2. 4 ). As a n o vel f or m ulati o n, t he effect of f o o d o n t he P K of sis u nat o vir 
a d mi nistere d as W G T
will be assesse d i n t his st u d y t o i nf or m d ose desi g n f or f ut ure st u dies.
4. 2. 1. C h oice of C o ntr ace pti o n/ B arrier Re q uire me nts
H u ma n re pr o d ucti ve safet y  data are li mite d f or sis u nat o vir, b ut 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. T heref ore , t he 
us e 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
T he d ose le vel use d i n t his st u d y  will be 
 m g. A d mi nistrati o n of sis u nat o vir 
 m g as a 
si n gle d ose or m ulti ple d oses was de m o nstrate d t o be safe a n d well -t olerate d i n c o m plete d 
a n d o n g oi n g cli nical st u dies (e g, C 5 2 4 1 0 0 1, C 5 2 4 1 0 0 2, C 5 2 4 1 0 0 4, C 5 2 4 1 0 0 5 , a n d 
C 5 2 4 1 0 0 6 ). Hi g her d oses of sis u nat o vir ( C 5 2 4 1 0 0 1, C 5 2 4 1 0 02) were als o de m o nstrate d t o 
be safe a n d well -t olerate d, pr o vi di n g a de q uate e x p os ure c o vera ge i n t he e ve nt of hi g her 
e x p os ures bei n g o bser ve d f or t he ne w W G T
f or m ulati o n. 
Sis u nat o vir  
 m g was de m o nstrate d t o be efficaci o us i n a vir us c halle n ge st u d y w here 
sis u nat o vir at  
 m g  
 × 
da ys was as efficaci o us as  
 m g
 ×
da ys i n 
re d uci n g viral l oa d a n d t otal s ym pt o m sc ores ; w hereas, t he 
-m g  d ose was ass ociate d wit h 
GI -relate d A Es (m ore detail s i n Secti o n 2. 2. 4 ). T h us, 
m g is t he pla n ne d P hase 2/ 3 d ose 
f or sis u nat o vir P hase 2/ 3 st u dies i n a d ults. In a d diti o n, w hile 
m g (t he l o west ta blet 
stre n gt h) c o ul d be c o nsi dere d f or t his st u d y, d ue t o t he o bser ve d n o n- li near P K i n c o m plete d 
st u dies (Secti o n 2. 2. 4 ), it is n ot use d i n t his st u d y as it ma y  n ot be pre dicti ve of 
m g
e x p os ure. 
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
or last sc he d ule d pr oce d ure s h o w n i n t he S o A f or t he last partici pa nt i n eac h part .
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 partici pa nt ha ve c o m plete d all 
peri o ds of e nr olle d p art(s), i ncl u di n g t he last visit or t he last sc he d ule d pr oce d ure s h o w n i n 
t he S o A (Ta ble 1 a n d Ta ble 2 ).
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 e nr olle d st u d y part(s), 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. If a 
prescree ni n g t o ol is utilize d f or st u d y recr uit me nt p ur p oses, it will i ncl u de c ollecti o n of 
i nf or mati on 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, race, a n d et h nicit y . T he f oll o wi n g eli gi bilit y  
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( 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

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 5
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.
Male a n d fe male partici pa nts a ge d 1 8 ye ars or ol der ( or t he mi ni m u m a ge of c o nse nt 
i n acc or da nce wit h l ocal re g ulati o ns) at scree ni n g w h o are o vertly 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 ys ical e xa mi nati o n, 
la b orat or y tests, a n d car diac e val uati o n.

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. 
Ot her I ncl usi o n Criteri a :
2.
B MI of 1 6 t o 32 k g/ m 2; a n d a t otal b o d y wei g ht >4 5 k g ( 1 0 0 l b). 
3.
Ca pa ble of g i 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 , 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 gical, or 
aller gic disease (i ncl u di n g dr u g all er 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, or H C V A b. He patitis B vacci nati o n is all o we d.
2.
A n y  me dical or ps yc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) 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 t hat ma y 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 6
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:
3.
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 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 ys 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 (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).
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
4.
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:
5.
A p ositi ve uri ne dr u g test, c o nfir me d b y a re peat e d test, if dee me d necessar y. 
6.
F or partici pa nts < 6 0 y ears: 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. F or partici pa nts 
≥6 0 y ears ol d, a scree ni n g s u pi ne B P of ≥1 5 0/ 9 0 m m H g ma y  be use d. If s yst olic B P 
is ≥ 1 4 0 or 1 5 0 m m H g ( base d o n a ge) or diast olic ≥9 0 m m H g, 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 eli gi bilit y.
7.
Sta n dar d 1 2 -lea d E C G t hat de m o nstrates cli nicall y 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 se ri o us bra d yarr h yt h mias or tac h yarr h yt 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 
eli gi bilit 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.
8.
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:

eG 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;
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 7

A S T or A L T le vel ≥1. 0 5 × U L N;

G G T > 1. 0 5 × U L N;

A L P > 1. 0 5 × U L N;

T otal bilir u bi n le vel ≥1. 0 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 :
9.
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 0. Hist or y  of se nsiti vit y t o sis u nat o vir or a ny of t he f or m u lati o n c o m p o ne nts.
1 1. 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 2. 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 3. 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 h e 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. T he i n vesti gat or or desi g nee will a d vise t he partici pa nt t o see k a d vice a b o ut t he 
d o nati o n a n d cr y o preser vati o n of ger m cells pri or t o t he start of st u d y  i nter ve nti o n, if 
a p plica ble.
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 hly 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 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 8
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 no l o n ger use a bsti ne nce 
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 
safety la b orat or y  e val uati o ns, a p pr o xi matel y 1 0 h o urs pri or t o t he d ose d uri n g Part 1
Peri o d s 1- 3 a n d Part 2 Peri o ds 1 - 2.
Part 1

O n D osi n g D a y  ( D a y 1) i n P eri o ds 1 a n d 2, l u nc h will be t he first meal wit h d osi n g 
after a n o ver ni g ht fast of a p pr o xi matel y  1 0 h o urs. Water is per mitte d u ntil 1
h o ur 
pri or t o st u d y  i nter ve nti o n a n d ma y be c o ns u me d wit h o ut restricti o n be gi n ni n g 1 h o ur 
after d osi n g.

O n D osi n g D a y  ( D a y 1 ) i n Peri o d 3, partici pa nts will be d ose d u n der 
hi g h -fat/ hi g h-cal orie meal c o n diti o n .

F oll o wi n g a n o ver ni g ht fast of a p pr o xi matel y 1 0 h o urs, partici pa nts s h o ul d start a 
hi g h -fat/ hi g h-cal orie brea kfast a p pr o xi matel y  3 0 mi n utes pri or t o a d mi nistrati o n 
of t he st u d y  i nter ve nti o n. T he brea kfast will be c o ns u me d o ver a p pr o xi matel y 
2 0 mi n utes wit h st u d y  i nter ve nti o n a d mi nistere d wit hi n a p pr o xi matel y 1 0 mi n utes 
after c o m pleti o n of t he meal. Partici pa nts will be e nc o ura ge d t o eat t he f ull meal. 
If partici pa nts are u na ble t o c o m plete t he e ntire meal, it will be d oc u me nte d. N o 
f o o d will be all o we d f or at least 4 h o urs p ost -d ose.

T he brea kfast will be a hi g h -cal orie/hi g h -fat test meal. T he test meal s h o ul d 
deri ve a p pr o xi matel y  1 5 0, 2 5 0 a n d 5 0 0-6 0 0 cal ories fr o m pr otei n, car b o h y drate 
a n d fat, res pecti vel y. T he f oll o wi n g brea kfast is a re prese ntati ve e xa m ple of a 
h i g h-fat, hi g h-cal orie meal: 2 e g gs frie d i n b utter, 2 stri ps of bac o n, 2 slices of 
t oast wit h b utter, 4 o u nces of has h br o w n p otat oes, 8 fl ui d o u nces ( 2 4 0 m L ) of 
w h ole mil k.
Part 2

O n D osi n g D a y  ( D a y 1) f or Treat me nt B, l u nc h will be t he first meal wit h d osi n g 
after a n o ver ni g ht fast of a p pr o xi matel y  1 0 h o urs. Water is per mitte d u ntil 1 h o ur 
pri or t o st u d y  i nter ve nti o n a n d ma y be c o ns u me d wit h o ut restricti o n be gi n ni n g 1 h o ur 
after d osi n g.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 9

O n D osi n g D a y  ( D a y 1) f or Treat me nt D, partici pa nts will be d o se d u n der 
l o w-fat/l o w-cal orie meal c o n diti o n.

F oll o wi n g a n o ver ni g ht fast of a p pr o xi matel y  1 0 h o urs, partici pa nts s h o ul d start a 
l o w-fat/l o w-cal orie brea kfast a p pr o xi matel y  3 0 mi n utes pri or t o a d mi nistrati o n of 
t he st u d y i nter ve nti o n. T he brea kfast will be c o ns u me d o ver a p pr o xi matel y  
2 0 mi n utes wit h st u d y  i nter ve nti o na d mi nistere d wit hi n a p pr o xi matel y 1 0 mi n utes 
after c o m pleti o n of t he meal. Partici pa nts will be e nc o ura ge d t o eat t he f ull meal. 
If partici pa nts are u na ble t o c o m plete t he e ntire meal, it will be d oc u me nte d. N o 
f o o d will be all o we d f or at least 4 h o urs p ost -d ose.

T he brea kfast will be a l o w-cal orie/l o w-fat test meal. T he test meal s h o ul d c o ntai n 
a t otal cal orie of 4 0 0-5 0 0 Kcal wit h ~ 1 0 0 - 1 2 5 Kcal ( ~ 2 5 %) deri ve d fr o m fat. T he 
f oll o wi n g brea kfast is a re prese ntati ve e xa m ple of a l o w-fat, l o w-cal orie meal: 
1 b oile d e g g, o ne pac ket fla v ore d i nsta nt oat meal ma de wit h wa ter, a n d 8 fl ui d 
o u nces ( 2 4 0 m L ) of 1 % fat mil k.
F or all Peri o ds i n b ot h Part 1 a n d Part 2 :

Water ca n be all o we d as desire d e xce pt f or
1 h o ur after st u d y  i nter ve nti o n 
a d mi nistrati o n.

T here are n o water restricti o ns pri or t o d osi n g f or partici pa nts d ose d u n der fe d 
c o n diti o ns. 

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.

L u 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.

Di n ner will be pr o vi de d a p pr o xi matel y  9 t o 1 0 h o urs after d osi n g.

A n e ve ni n g s nac k ma y  be per mitte d.

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 matel y 3 2 0 0 kcal.
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. 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 0

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 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 n ic 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 xercise (e g, hea v y 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 da ys, 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. 3 .
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 HE 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 a u xiliar y 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.
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
Sis u nat o vir
T y pe
Dr u g
Use
E x peri me ntal
I M P or NI M P/ A x M P
I M P
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 1
St u d y I nter ve nti o n(s)
I nter ve nti o n N a me
Sis u nat o vir
D ose F or m ul ati o n
PI C or W G T
U nit D ose Stre n gt h(s)
 m g f or PI C or  
 m g f or W G T
D os a ge Le vel(s)
 m g
R o ute of A d m i nistr ati o n
Oral
S o urci n g
Pr o vi de d ce ntrall y b y t he s p o ns or
P ac k a gi n g a n d L a beli n g
T he sis u nat o vir 
 m g ca ps ules a n d 
m g ta blets 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.
S R S D
I B
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
P art 1 St u d y Ar m(s)
A r m  Title
Treat me nt A
Treat me nt B
Treat me nt C
A r m  T y pe
E x peri me ntal
E x peri me ntal
E x peri me ntal
A r m  Descri pti o n
Partici pa nts will recei ve a 
si n gle  
 m g d ose of 
sis u nat o vir PI C 
a d mi nistere d orall y as 
sis u nat o vir   m g 
ca ps ules u n der faste d 
c o n diti o ns.
Partici pa nts will recei ve 
a si n gle  
 m g d ose of 
sis u nat o vir W G T 
a d mi nistere d orall y as 
sis u nat o vir  
 m g 
ta blets u n der faste d 
c o n diti o ns.
Partici pa nts will recei ve a 
si n gle 
 mg d ose of 
sis u nat o vir W G T 
a d mi nistere d orall y as 
sis u nat o vir  
 m g 
ta blets wit h a hi g h -fat
meal .
P art 2 St u d y Ar m(s)
A r m  Title
Treat me nt B
Treat me nt D
A r m  T y pe
E x peri me ntal
E x peri me ntal
A r m  
Descri pti o n
Partici pa nts will recei ve a si n gle  
 m g 
d ose of sis u nat o vir W G T a d mi nistere d 
orall y as
sis u nat o vir  
 m g ta blets 
u n der faste d c o n diti o ns .
Partici pa nts will recei ve a si n gle  
 m g 
d ose of sis u nat o vir W G T a d mi nistere d 
orall y as sis u nat o vir  
 m g ta blets wit h a
l o w-fat meal.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( 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
C CI
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 2
Sis u nat o vir will be pr o vi de d b y  Pfizer as
-m g  PI Cs a n d
-m g W G T s.
T he ca ps ules a n d ta blets 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.
6. 1. 1. A d mi nistr ati o n
A d mi nistrati o n of st u d y  i nter ve nti o n(s) at t he site will be perf o r me d by a n a p pr o priatel y 
q ualifie d a n d trai ne d me m ber of t he st u d y staff as all o we d b y l ocal, state, a n d i nstit uti o nal 
g ui da nce. 
F oll o wi n g a d mi nistrati o n of st u d y i nter ve nti o n(s) at t he site, partici pa nts will be o bser ve d f or 
ti me of resi de nce wit hi n C R U b y  a n a p pr o priately q ualifie d a n d trai ne d me m ber of t he st u d y 
staff. A p pr o priate me dicati o n a n d ot her s u p p orti ve meas ures f or ma na ge me nt of a me dical 
e mer ge nc y will be a vaila ble i n acc or da nce wit h l ocal g ui deli nes a n d i nstit uti o nal g ui deli nes.
6. 1. 1. 1. P art 1
6. 1. 1. 1. 1. Peri o ds 1 a n d 2
F oll o wi n g a n o ver ni g ht fast of a p pr o xi matel y 1 0 h o urs, 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). 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 bient 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 . Partici pa nts 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. T his will be d oc u me nte d b y t he site. Partici pa nts 
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. 
6. 1. 1. 1. 2. Peri o d 3
F oll o wi n g a n o ver ni g ht fast of a p pr o xi matel y 1 0 h o urs, partici pa nts will recei ve st u d y  
i nter ve nti o n at a p pr o xi mately 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 hi g h -fat/ hi g h-cal orie 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. 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 . Partici pa nts 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. T his will be 
d oc u me nte d b y t he site. Partici pa nts 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. 
6. 1. 1. 2. P art 2
6. 1. 1. 2. 1. Tre at me nt B
F oll o wi n g a n o ver ni g ht fast of a p pr o xi matel y  1 0 h o urs, 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). 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 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 . Partici pa nts 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. T his will be d oc u me nte d b y t he site. Partici pa nts 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 on pri or t o 
s wall o wi n g. 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)
C CI
C CI

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 3
6. 1. 1. 2. 2. Tre at me nt D
F oll o wi n g a n o ver ni g ht fast of a p pr o xi matel y  1 0 h o urs, 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 ( ± 2 h o urs) a p pr o xi matel y  3 0 mi n utes after t he start 
of a l o w -fat brea kfast t hat will be c o nsu me d o ver a p pr o xi matel y  2 0 mi n utes. 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 . Partici pa nts 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. T his will be d oc u me nte d b y t he site. 
Partici pa nts 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. 
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 mai 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  s u 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 mat e 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 si nce pre vi o usly 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 ng wit h acti o ns ta ke n. T he site s h o ul d acti vel y 
p urs ue o pti o ns f or ret ur ni n g t he st u d y i nter 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 l ocal/site 
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 by t he st ora ge 
c o n diti o ns state d o n t he la bel.
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 venti o n acc o u nta bilit y 
f or m/rec or d.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 4
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 l ocal/site 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 plia 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.
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 w it hi n 1 b usi ness da y  of 
disc o ver y .
6. 2. 1. 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 mita nt 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.
Sis u nat o vir PI C s a n d W G T s 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 priately 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 hys icia n, n urse, p h ysicia 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 sis u nat o vir ta blets a n d 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 nc e 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 will assi g n partici pa nt n u m bers t o t he partici pa nts 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.
6. 4. Bli n di n g
T his is a n o pe n -la bel st u d y. 
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 w ill 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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 5
6. 6. D ose M o dific ati o n
D ose m o dificati o n is n ot all o we d f or t his st u d y .
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 ose
F or t his st u d y , a n y d ose of sis u nat o vir greater t ha n 3 0 0 m g as si n gle d os e or > 6 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.
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 n y 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 f oll o w u p 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 Sect i o n 7. 3).
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 n it 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 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 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 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 ys 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 ma y be per mitte d o n a case-b y -case basis 
f oll o wi n g a p pr o val by 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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 6
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 pr i 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.
Pr o hi bite d D uri n g t he St u d y

Me dicati o ns t hat ca n pr ol o n g Q T or Q Tc. O ne res o urce a vaila ble t o assess w het her a 
dr u g ma y  pr ol o n g Q T i ncl u des: H o me: Cre di ble me ds (htt ps://cre di ble me ds. or g) .
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
Si nce t his is a si n gle -d ose st u d y , t his secti o n is n ot a p plica ble.
7. 1. 1. P ote nti al C as es of Ac ute Ki d ne y I nj ur y
Partici pa nts e x p ose d t o I M P de m o nstrati n g tra nsie nt or s ustai ne d i ncrease i n Screat ( wit h 
decrease i n Screat -base d e G F R or e Cr C l) re q uire e x pe dite d e val uati o n t o differe ntiate A KI 
fr o m DI CI. DI CI is defi ne d as tra ns p orter-me diate d effect relate d t o altere d re nal t u b ular 
creati ni ne ha n dli n g wit h o ut hist ol o gical i nj ur y .
A KI m a y  be d ue t o o ne or m ore ty pes of i nj ur y, i ncl u di n g DI KI. Differe ntiati o n of DI KI 
fr o m ot her ca uses of A KI a n d fr o m DI CI ma y re q uire cli nical, ra di o gra p hic, hist o pat h ol o gic, 
a n d la b orat or y assess me nts, as well as ne p hr ol o g y c o ns ultati o n.
F oll o w -u p Assess me nts
T he partici pa nt s h o ul d ret ur n t o t he site f or e val uati o n as s o o n as p ossi ble, prefera bl y wit hi n 
4 8 h o urs of a ware ness of t he a b n or mal res ults. 
E val ua ti o n s h o ul d i ncl u de p h ysical e xa mi nati o n, la b orat or y tests, detaile d me dical a n d 
s ur gical hist or y, re vie w of all me dicati o ns (i ncl u di n g recreati o nal dr u gs a n d s u p ple me nts 
[ her bal]), fa mil y hist or y, se x ual hist or y, tra vel hist or y, bl o o d tra nsf usi o n, a n d p ote ntial 
occ u pati o nal e x p os ure t o c he micals. 
La b orat or y  assess me nts s h o ul d i ncl u de si m ulta ne o us ser u m c ystati n C ( Sc ys) a n d ser u m 
creati ni ne ( Screat) tests. Esti mates of e G F R, e Cr Cl a n d Screat -base d e G F R a n d c o m bi ne d 
Screat -S c y s-base d e G F R s h o ul d als o be de ri ve d usi n g t he a p pr o priate e q uati o n descri be d i n 
A p pe n di x 6 .
If a p pr o priate, ne p hr ol o g y c o ns ultati o n ma y be rec o m me n de d t o facilitate differe ntiati o n of 
re nal pare nc hy m al disease, pre-re nal az ote mia, a n d p ost-re nal o bstr ucti o n. 
Assess me nts of uri ne al b u mi n -t o-creati ni ne rati o or uri ne v ol u me ma y  als o be perf or me d as 
a p pr o priate.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 7
Differe nti ati n g Ac ute Ki d ne y I nj ur y fr o m DI CI
A c o nfir me d Screat i ncrease is defi ne d as:
(i) ≥0. 3 m g/ d L ( ≥2 6. 5 µ m ol/ L) wit hi n 4 8 h o urs O R 
(ii) c o nfir me d Screat i ncrease ≥1. 5 ti mes baseli ne ( k n o w n or s us pecte d t o ha ve occ urre d 
wit hi n t he pri or 7 da y s). 
Base d o n t he assess me nts perf or me d, s us pecte d A KI (i ncl u di n g DI KI) ma y be differe ntiate d 
fr o m DI CI as f oll o ws.
A d ult p artici p a nts
A KI (i ncl u di n g DI KI)
A n y o ne of t he bel o w
DI CI
Sc ys & Screat
Si m ulta ne o us, c o nfir me d ser u m c ystati n 
C ( Sc ys) i ncrease a n d c o nfir me d Screat 
i ncrease 
C o nfir me d Screat i ncrease wit h o ut 
c o nfir me d i ncrease i n refle x Sc ys 
A N D 
C o nfir me d Screat -base d e G F R 
decrease wit h o ut c o nfir me d c o m bi ne d 
Screat -Sc ys -base d e G F R decrease.
e G F R
Decrease i n Screat -base d e G F R a n d 
c o m bi ne d Screat -Sc ys -base d e G F R ( w he n 
a vaila ble)
Al b u mi n uria or 
pr otei n uria
C o nfir me d al b u mi n uria i ncrease (see 
A p pe n di x 6 f or Gra des A 1 t o A 3 
q ua ntitati o n)
Uri ne v ol u me
Uri ne v ol u me < 0. 5 m L/ k g/ h f or 
6 c o nsec uti ve h o urs
Re gar dless of t he prese nce or a bse nce of i ncrease i n Screat, DI KI a n d ot her ca uses of A KI 
ma y  be s us pecte d if eit her t here is (i) ne w-o nset or w orse ni n g al b u mi n uria or pr otei n uria are 
detecte d.
All c o nfir me d cases of cli nicall y  rele va nt decrease i n ki d ne y f u ncti o n s h o ul d be c o nsi dere d 
p ote ntial cases of DI KI if n o ot her reas o n f or t he ki d ne y  f u ncti o n a b n or malities has bee n 
f o u n d.
7. 1. 2. E C G C h a n ges
A p artici pa nt w h o meets eit her b ullete d criteri o n base d o n t he a vera ge of tri plicate E C G 
rea di n gs will be wit h dra w n fr o m t he st u dy i nter ve nti o n. 

Q Tc F > 5 0 0 ms.

C ha n ge fr o m baseli ne: Q Tc F > 6 0 ms.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 8
If a cli nicall y si g nifica nt fi n di n g is i de ntifie d (i ncl u di n g, b ut n ot li mite d t o, c ha n ges fr o m 
baseli ne i n Q Tc F after e nr oll me nt), t he i n vesti gat or or q ualifie d desi g nee will deter mi ne if 
t he partici pa nt ca n c o nti n ue i n t he st u d y a n d if a n y c ha n ge i n partici pa nt ma na ge me nt is 
nee de d. T his re vie w of t he E C G pri nte d at t he ti me of c ollecti o n m ust be d oc u me nte d. A ny 
ne w cli nicall y rele va nt fi n di n g s h o ul d be re p orte d as a n A E.
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 bl e, 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. 
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.
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 wi ll 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 n y  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 t he 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 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 9
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 -U p 
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 c o m plete 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 ke 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 nta ct 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 priate 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. 
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 eli 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 n ts will be scree ne d wit hi n 2 8 da y s pri or t o a d mi nistrati o n of t he st u d y i nter ve nti o n 
i n eit her Part 1 or Part 2 , 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 da y s as a res ult of u ne x pecte d dela y s 
(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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 0
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 p s 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.
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 olle cte d pri or t o t he i nserti o n of t he cat heter.
F or sa 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 h e t otal bl o o d sa m pli n g v ol u me f or i n di vi d ual partici pa nt s i n t his st u d y is a p pr o xi matel y 
1 6 0 m L i n Part 1 a n d a p pr o xi matel y 1 2 0 m L i n Part 2 . 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 by Pfizer, pr o vi de d t he t otal 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 a n d C o nc o mita nt T hera p y secti o ns 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
Efficac y  para meters are n ot e val uate d i n t his st u d y. 
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, car di o vasc ular, a n d GI s yste ms, a n d partici pa nt -re p orte d sy m pt o ms.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 1
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 c o 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 exa 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 rec or d 
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 ys ical 
e xa mi nati 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 
( 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. Par tici pa nts 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 na l 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
Sta n dar d 1 2 -lea d E C Gs will 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 Tc F, 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 f ull 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.
T o e ns ure safet y of t he partici pa nts, 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) a 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 2
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 n y 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 2 a d diti o nal E C Gs will be c ollecte d a p pr o xi matel y  2 t o 4 mi n utes a part t o c o nfir m t he 
ori gi nal meas ure me nt. If t he Q Tc F val ues fr o m t hese re peate d E C Gs re mai n a b o ve t he 
t hres h ol d val ue, t he n a si n gle E C G m ust be re peate d at least h o url y u ntil Q Tc 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 n y 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 Tc F 
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). 
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 t he E C G a b n or malit y . 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 v i 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 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 issues .
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 s t u d y or wit hi n 4 8 h o u rs 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 a n d t he s p o ns or n otifie d.
See A p pe n di x 5 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 .
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 3
See A p pe n di x 6 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. Pre g n a nc y Testi n g
A uri ne or 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 
starti 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 uri 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 
(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 ve nts 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 clas sificati o n as a n S A E or ca use d t he partici pa nt t o disc o nti 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, e ac 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 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 4
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 nues 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 beca use of a n A E 
or S A E, t he 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.
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 wever, if t he i n vesti gat or lear ns of a n y 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 ncl u de d st u d y partici pati o n , 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 d y  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 assist 
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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 5
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 di n g, e val uati n g, a n d assessi n g ca usalit y of AEs a n d S A E s 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 ).
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 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 6
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.

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 Pfize r 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 re gar dless 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 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.

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 p y of t he 
c o m plete d re p ort is mai ntai ne d i n t he i n vesti gat or site file.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 7
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 re p ort. In t he case of a li ve birt h, t he str uct ural i nte gri t y of t he ne o nate 
ca n be assesse d at t he ti me of 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 nically p ossi ble, t he str uct ural i nte grit y of t he 
ter mi nate d fet us s h o ul d be assesse d by gr oss vis ual i ns pec ti o n ( u nless pre-pr oce d ure test 
fi n di n gs are c o ncl usi ve f or a c o n ge nital a n o maly a n d t he fi n di n gs are re p orte d).
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 neo us a b orti o n, i ntra uteri ne fetal 
de mise, ne o natal 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 r e 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 m a y  be re q ueste d b y t he s p o ns or. F urt her 
f oll o w- 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 pant 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. 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 8
T he i n vesti gat or m ust re p ort E D B 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 nf or mati o n m ust be re p o rte 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 re p ort 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 .
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 o r 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 re p ort is 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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 9
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 ;

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, suc h me dicati o n err ors occ urri n g t o a st u d y  partici pa nt are rec or de 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 a n d, if 
a p plica ble, a n y ass ociate d seri o us a n d n o nseri o us A E(s), 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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 0
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 0.5 m L  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 . 
I nstr ucti o ns f or t he c ollecti o n a n d ha ndli 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. 
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 o si 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 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.
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 mai ntai 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 m a 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.
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. 6. 2. Ret ai ne d Rese arc h S a m ples f or Ge netics
Retai ne d researc h sa m ples f or ge netics are n ot c ollecte 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 .
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 1
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 h e data c ollecte d i n t his st u d y 
is o utli ne d here a n d 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 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
T here is n o statistical h y p ot hesis f or t his st u d y .
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 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/assi g n me nt t o st u d y i nter ve nti 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 ny st u d y acti vit y 
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 dy, 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 oll e d, u nless 
ot her wise s pecifie d b y t he pr ot oc ol.
E val ua b le
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.
Safet y
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.
P K Para meter Set
All ra n d o mize d partici pa nts w h o recei ve at least o ne d ose of 
st u d y me dicati o n a n d i n w h o m at least 1 plas ma P K para meter 
is calc ulate d.
P K C o nce ntrati o n Set
All ra n d o mize d partici pa nts w h o recei ve at least 1 d ose of 
st u d y me dicati o n a n d i n w h o m at least 1 plas ma c o nce ntrati o n 
val ue is re p orte d.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 2
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 e rf 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 .
All treat me nt ar ms will be re p orte d se paratel y.
9. 3. 1. 1. Deri v ati o n of P h ar m ac o ki netic P ar a meters
P K para meters f or sis u nat o vir will be deri ve d fr o m t he c o nce ntrati o n-ti me pr ofiles usi n g 
n o nc o m part me ntal met h o ds as data per mit. T he P K para meters t o be assesse d i n t his st u d y , 
t heir defi niti o n, a n d met h o d of deter mi nati o n are o utli ne d i n Ta ble 8 . I n all cases, act ual P K 
sa m pli n g ti mes will be use d i n t he deri vati o n of P K para meters w he n a vaila ble . I n t he case 
t hat act ual P K sa m pli n g ti mes are n ot a vaila ble, n o mi nal P K sa m pli n g ti me will be use d i n 
t he deri vati o n of P K para meters.
T a ble 8 .
Pl as m a P K P ar a meters
P ar a meter
Defi niti o n
Met h o d of Deter mi n ati o n
A U C last
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 t he ti me of t he last 
q ua ntifia ble c o nce ntrati o n ( C last)
Li near/ L o g tra pez oi dal met h o d.
A U C i nfa
Area u n der t he plas ma
c o nce ntrati o n-ti me pr ofile fr o m 
ti me 0 e xtra p olate d t o i nfi nite 
ti me
A U C last + ( C last*/ k el),
w here C last* is t he pre dicte d plas ma 
c o nce ntrati o n at t he last q ua ntifia ble 
ti me p oi nt esti mate d fr o m t he l o g-
li near re gressi o n a nalys is.
C ma x
Ma xi m u m o bser ve d plas ma
C o nce ntrati o n
O bser ve d directl y fr o m data.
T ma x
Ti me t o reac h C ma x
O bser ve d directl y fr o m data as ti me 
of first occ urre nce.
t½ a
Ter mi nal half -life
L o g e( 2)/ kel,
w here k el is t he ter mi nal p hase rate 
c o nsta nt calc ulate d b y a li near 
re gressi o n of t he l o g-li near
c o nce ntrati o n-ti me c ur ve. O nl y 
t h ose data p oi nts j u d ge d t o descri be 
t he ter mi nal l o g-li near decli ne will 
be use d i n t he re gressi o n.
C L / Fa
A p pare nt cleara nce
D ose/ A U C i nf.
V z/ Fa
A p pare nt v ol u me of distri b uti o n
D ose/( A U C i nf • k el).
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 3
T a ble 8 .
Pl as m a P K P ar a meters
P ar a meter
Defi niti o n
Met h o d of Deter mi n ati o n
a.
As data per mits. 
9. 3. 2. Pri m ar y E n d p oi nt(s) A n al ysis
P las ma A U C last, A U C i nf (if data per mit) a n d C ma x will be s u m marize d descri pti vel y  b y 
treat me nt. T he plas ma c o nce ntrati o ns of sis u nat o vir will be liste d a n d descri pti vel y 
s u m marize d b y n o mi nal P K sa m pli n g ti me a n d treat me nt. I ndi vi d ual partici pa nt a n d 
s u m mar y pr ofiles ( mea n a n d me dia n pl ots) of t he plas ma c o nce ntrati o n-ti me data will be 
pl otte d b y  treat me nt usi n g act ual a n d n o mi nal ti mes, res pecti vel y. Mea n a n d me dia n pr ofiles 
will be prese nte d o n b ot h li near a n d se mi- l o g scales.
9. 3. 3. Sec o n d ar y E n d p oi nt(s) A n al ysis
9. 3. 3. 1. S afet y A n al ys es
All safet y a nal ys es will be perf or me d o n t he safet y p o p ulati o n.
A Es, E C Gs, B P, p ulse rate, a n d safet y  la b orat or y data 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 safety of partici pa nts. A n y cli nical 
la b orat or y, E C G, B P, a n d p ulse 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 , p h y sical e xa mi nati o n, a n d ne ur ol o gical e xa mi nati o n 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 gs 
i de ntifie d o n p h ysical a n d/ or ne ur ol o gical e xa mi nati o ns 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 u si o n/e xcl usi o n criteria, s uc h as la b orat or y 
data, E C Gs, a n d vital 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 n ts 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 fr o m baseli ne i n t he f oll o wi n g cate g ories will be ta b ulate d: 
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
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 4
9. 3. 3. 2. Ot her Sec o n d ar y E n d p oi nts A n al yses
Part 1
T o c o m pare t he Treat me nts A ( PIC u n der faste d c o n diti o n ) a n d B (W G T
u n der faste d 
c o n diti o n ), nat ural l o g tra nsf or me d A U C last, A U C i nf (if data per mit) a n d Cma x of sis u nat o vir 
will be a nal yz e d se paratel y usi n g a mi xe d effect m o del wit h se q ue nce ( A B or B A), peri o d 
a n d treat me nt i ncl u de d as fi xe d effects a n d partici pa nt neste d wit hi n se q ue nce as a ra n d o m 
effect. O nl y data fr o m t he first 2 st u d y peri o ds will be use d i n t he a nalys is. Esti mates of t he 
a dj uste d mea n differe nces ( Test -Refere nce) a n d c orres p o n di n g 9 0 % CIs will be o btai ne d 
fr o m t he m o del. T he a dj uste d mea n differe nces a n d 9 0 % CIs f or t he differe nces will be 
e x p o ne ntiate d t o pr o vi de esti mates of t he rati o of a dj uste d ge o metric mea ns ( Test/ Refere nce) 
a n d 9 0 % CIs f or t he rati os. Treat me nt A is t he Refere nce treat me nt a n d Treat me nt B is t he 
Test treat me nt.
F or t he hi g h -fat f o o d effect e val uati o n, nat ural l o g tra nsf or me d nat ural l o g tra nsf or me d 
A U C last, A U C i nf (if data per mit) a n d Cma x of sis u nat o vir will be a nal yz e d usi n g a mi xe d effect 
m o del wit h se q ue nce, a n d treat me nt as fi xe d effects a n d partici pa nt wit hi n se q ue nce as a 
ra n d o m effect. Esti mates of t he a dj uste d mea n differe nces ( Test- Refere nce) a n d 
c orres p o n di n g 9 0 % CIs will be o btai ne d fr o m t he m o del. T he a dj uste d mea n differe nces a n d 
9 0 % CI s f or t he differe nces will be e x p o ne ntiate d t o pr o vi de esti mates of t he rati o of 
a dj uste d ge o metric mea ns ( Test/ Refere nce) a n d 9 0 % CI  f or t he rati os. Treat me nt B (W G T
u n der faste d c o n diti o n) is t he Refere nce treat me nt a n d Treat me nt C (W G T
wit h hi g h -fat 
meal ) is t he Test treat me nt. F or t he f o o d effect c o m paris o n o nl y t he data fr o m Treat me nts B 
a n d C will be i ncl u de d i n t he m o del.
Part 2
F or t he l o w-fat f o o d effect e val uatio n, nat ural l o g tra nsf or me d A U C last, A U Ci nf (if data 
per mit) a n d C ma x of sis u nat o vir will be a nal yz e d usi n g a mi xe d effect m o del wit h se q ue nce, 
a n d treat me nt as fi xe d effects a n d partici pa nt wit hi n se q ue nce as a ra n d o m effect. Esti mates 
of t he a dj uste d mea n differe nces ( Test -Refere nce) a n d c orres p o n di n g 9 0 % CI s will be 
o btai ne d fr o m t he m o del. T he a dj uste d mea n differe nces a n d 9 0 % CIs f or t he differe nces will 
be e x p o ne ntiate d t o pr o vi de esti mates of t he rati o of a dj uste d ge o metric mea ns 
( Test/ Refere nce) a n d 9 0 % CI  f or t he rati os. Treat me nt B ( W G T u n der faste d c o n diti o n) is t he 
Refere nce treat me nt, Treat me nt D ( W G T wit h l o w-fat meal) is t he Test treat me nt. 
9. 3. 4. Terti ar y/ E x pl or at or y E n d p oi nt(s) A n al ysis
T he a nal ys is of tertiar y/e x pl orat or y e n d p oi nts will be detaile d i n t he S A P.
9. 3. 5. Ot her A n al yses 
P har mac o ge n o mic or bi o mar ker data fr o m Retai ne d Researc h Sa m ples ma y  be c ollecte d 
d uri n g or after t he trial a n d retai ne d f or f ut ure a nal yses; t he res ults of s uc h a nal ys es are n ot 
pla n ne d t o be i ncl u de d i n t he C S R.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 5
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. 
9. 5. S a m ple Size Deter mi n ati o n
A s ufficie nt n u m ber of partici pa nts will be scree ne d t o ac hie ve a p pr o xi matel y 1 2 partici pa nts 
ra n d o mize d t o st u d y i nter ve nti o n. T he sa m ple size is e m piricall y sele cte d a n d is n ot base d o n 
statistical p o wer calc ulati o n. Partici pa nts w h o disc o nti n ue fr o m t he st u d y  f or n o n-safet y 
reas o ns ma y be re place d at t he s p o ns or’s discreti o n i n c olla b orati o n wit h t he i n vesti gat or.
T he e x pecte d wi dt hs of t he 9 0 % CIs wit h 8 0 % c o ver a ge pr o ba bilit y f or a ra n ge of p ossi ble 
effects ( Test vs Refere nce) are s h o w n i n Ta ble 9 bel o w. T he calc ulati o n ass u mes a 
wit hi n -partici pa nt sta n dar d de viati o ns of 0. 3 4 f or l o g e( A U C) a n d 0. 3 8 f or l o ge( Cma x ) base d o n 
a vaila ble D a y  1 data of st u d y  C 5 2 4 1 0 0 6.
T a ble 9 .
E x pecte d Wi dt hs of t he 9 0 % CIs ( wit h 8 0 % C o ver a ge Pr o b a bilit y) f or 
Differe nt P ossi ble Rel ati ve Effect Esti m ates at N = 1 2
Esti m ate d 
Effect 
( Test/ Refere nce)
A U C
C m a x
9 0 % CI
CI wi dt h
9 0 % CI
CI wi dt h
5 0 %
3 7 % t o 6 7 %
3 0 %
3 6 % t o 6 9 %
3 3 %
7 5 %
5 6 % t o 1 0 0 %
4 4 %
5 4 % t o 1 0 4 %
5 0 %
1 0 0 %
7 5 % t o 1 3 4 %
5 9 %
7 2 % t o 1 3 9 %
6 6 %
1 2 5 %
9 3 % t o 1 6 7 %
7 4 %
9 0 % t o 1 7 3 %
8 3 %
1 5 0 %
1 1 2 % t o 2 0 1 %
8 9 %
1 0 8 % t o 2 0 8 %
1 0 0 %
1 7 5 %
1 3 1 % t o 2 3 4 %
1 0 4 %
1 2 6 % t o 2 4 2 %
1 1 6 %
2 0 0 %
1 4 9 % t o 2 6 8 %
1 1 8 %
1 4 4 % t o 2 7 7 %
1 3 3 %
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 6
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 T I 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 m e n d me nts, IC 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 I R 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 hea lt h a ut h orit y 
a p pr o val pri 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 nuall 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 mi g 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 7
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 vest i gat or t o pr otect t he st 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. Fi n a nci al Discl os ure
I n vesti gat ors a n d s u bi n vesti gat ors will pr o vi de t he s p o ns or wit h s ufficie nt, acc urate fi na ncial 
i nf or mati o n as re q ueste d t o all o w t he s p o ns or t o s u b mit c o m plete a n d acc urate fi na ncial 
certificati o n or discl os ure state me nts t o t he a p pr o priate re g ulat or y  a ut h orities. I nvesti gat ors 
are res p o nsi ble f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t he c o urse of t he st u d y 
a n d f or 1 ye ar after c o m pleti o n of t he st u d y .
1 0. 1. 3. 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 an 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 trial.
Partici pa nts m ust be i nf or me d t hat t hei r 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 uire me nts, w here 
a p plica ble, a n d t he I R B/ E C or s t 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 ori ties.
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 s i 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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 8
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 i s rescree ne d is n ot re q uire d t o si g n a n ot her I C D 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.
1 0. 1. 4. 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 orized 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 w ill 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 S O Ps 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. 5. C o m mittees Str uct ure
1 0. 1. 5. 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. 6. Disse mi n ati o n of Cli 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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 9
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.
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 ve nti 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 pro 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 pl ica 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 d me 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 
inf 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 yses. 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 nfl icts 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. 7. 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 nte 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 gnee electr o nicall y  (e g, la b orat or y data). T he i n vesti gat or is 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 0
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.
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 vest i 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 d y c o m pleti o n. It 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 uire me 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 part y wit h o ut writte 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 bly delete d fr o m all s yste ms.
T he i n vesti gat or(s) w ill 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 1
1 0. 1. 8. 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 nter e 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.
D efi 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 C R 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 hat 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. 9. 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 oll o 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 nsor 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 2

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 nizat i 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 sys 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 pro 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. 1 0. 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’s 
desi g nee ( Pfizer C R U) if re q ueste d t o d o s o b y 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 n y 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 1. 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 3
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 parati 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 uireme 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 ty 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 wil l 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 Pfiz er. 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 n y 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 nal ys 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 blicati 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 nd 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 
discl 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 nshi 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 2. 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 i n 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 n-st u d y healt hcare pr ofessi o nals, participa 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 
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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 4
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 ma y 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 ory, or as deri ve d 
fr o m calc ulate d val ues; f or e xa m ple: calc ulati o n of esti mate d ki d ne y f u ncti o n (ie, 2 0 2 1 
C K D -E PI  e G F R [a d ults o nl y], as sta n dar d la b safet y test f or FI H a n d M A D st u dies). 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 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 dy t o assess a n y 
percei ve d safet y  iss ues.
T a ble 7 .
Pr ot oc ol -Re q uire d 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
Creati ni ne
C ystati n C a
e G F R, e Cr Cl b
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
T otal bi lir u bi n
Al kali ne p h os p hatase
Uric aci d
Al b u mi n
T otal pr otei n
G G T
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 c
At scree ni n g:
F S H d
Uri ne dr u g scree ni n g e
H Bs A g
H Bs A b
H Bc A b
H C V A b
HI V
Pre g na nc y test ( β -h C G) f
a.
C ystati n C ( Sc ys): Scree ni n g or Baseli ne Sc ys is rec o m me n de d t o hel p differe ntiate p ost -baseli ne DI KI 
fr o m DI CI. P ost- baseli ne, Sc ys is meas ure d if a n d o nl y if ser u m creati ni ne i ncrease p ost -baseli ne is o bser ve d 
(see Secti o n 7. 1. 1 ).
b.
Scree ni n g a n d Baseli ne e G F R or e Cr Cl is m eas ure d wit h Screat -base d f or m ula. A ge -s pecific ki d ne y 
f u ncti o n calc ulati o n (see Secti o n 1 0. 6. 2 ) is rec o m me n de d t o assess prese nce or a bse nce of p ost-baseli ne 
c ha n ge i n ki d ne y f u ncti o n .
c.
O nl y if U TI 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 .
d.
F or c o nfir mati o n of p ost me n o pa usal stat us o nl y i n fe males < 6 0 years ol d a n d n ot usi n g h or m o nal or 
H R T o nl y .
e.
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 hers are site - a n d st u d y-s pecific). Uri ne dr u g scree ni n g will als o be c o n d ucte d at 
A d missi o n.
f.
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 testi n g is re q uire d b y l ocal re g ulati o n 
or I R B/ E C. See S o A f or c ollecti o n ti mes.
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.
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 afte r d ose a d mi nistrati o n ma y be retai ne d a n d 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 5
st ore d f or t he d urati o n 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 b e 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 6
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  d osi 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 eit her 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 7
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 to 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 ocial 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 os 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 E s. 
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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 8
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 his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce, s uc h as u nc o m plicate d hea dac he, na usea, vo 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 mac 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 pri ate.
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 ples 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) 
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. 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 9
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 the 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 dical 
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 ortin 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 0

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 . 1.9 f or acti o ns 
t hat 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 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 c li 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 ym 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.

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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 1

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 n s ult t he I B a n d/ or pr 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 ha ve 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 situati 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 he 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 po 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 
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 u di n g hist o pat h ol o g y.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 2

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 E s
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.

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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 3
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 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 re pr o d ucti ve safety 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) an 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 b el 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 (a) is n ot pre g na nt or breastfee di n g; ( b) 
a grees t o n ot d o nate e g gs ( o va, o oc y tes) f or t he p ur p ose of re pr o d ucti o n f or at least 2 8 da y s
after t he last d ose of t he st u d y  i nter ve nti o n; a n d (c) 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 w h o 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) wit h l o w user de pe n de nc y 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 safety ris k of t he st u d y i nter ve nti o n(s). T he 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 4
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 hi g hl y 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 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 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). 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 wi n g t he w o ma n’s me dical hist or y, me nstr ual hist or y ,
a n d rece nt se x ual acti vit y i n or der t o decrease t he ris k of e nr olli n g a w o ma n wit h a n earl y, 
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.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 5
2.
P ost me n o pa usal fe male .

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 v e 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 
6.
C o m bi ne d (estr o ge n - a n d pr o gest o ge n -c o ntai ni n g) h or m o nal 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 ntra va gi nal + b arrier*
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 6

Tra ns der m al + b arrier *
7.
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 *
8.
Se x ual A bsti ne nce
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 val uate 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 ns 6 or 7 f or t he st u dy 
i ncl u de a ny 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 7
1 0. 5. A p pe n di x 5 : 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
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/are 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 ote 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 medical e ve nts, e ve n 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 ormal 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).
Rises i n A S T/ A L T a n d T b ili se parate d by 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. 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 8
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, e osi n o p hils ( %), 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 nalys es 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 mati o 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 by 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 , t otal bile aci ds, 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 9
1 0. 6. A p pe n di x 6 : Ki d ne y S afet y: M o nit ori n g G ui deli nes
1 0. 6. 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 o nfir 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 ys is i n dicate d:
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 u late 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. 6 . 2. 1.) a n d by 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). 
1 0. 6. 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. 6. 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) [9 ]
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
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. 6. 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 
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 0
f or m ulae (see Secti o n 1 0. 6. 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
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 are use d f or ser u m creati ni ne ( m g/ d L o nl y), ser u m c ystati n 
C ( m g/ L o nl y ), t otal b o d y wei g ht ( k g o nl y), a n d a ge ( years). I n vesti gat ors are e x pecte d t o (i) 
re vie w a n 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 versi 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. 6. 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 f or b ot h pediatric a n d a d ult 
partici pa nts .
K DI G O criteri a
gr a de ( G)
St u d y 
P o p ul ati o n
G 1  
G 2  
G 3  
G 4  
G 5
Decre ase d Ki d ne y 
F u ncti o n d ue t o 
eit her Ac ute or 
C hr o nic Ki d ne y 
I nj ur y 
A d ult 
partici pa nts
e G F R 
(m L/ mi n/ 1. 7 3 m ²)
≥9 0 
≥6 0 t o 8 9
3 0 t o 5 9 
1 5 t o 2 9
< 1 5
K DI G O al b u mi n uri a ( A) 
criteri a
A 1
A 2
A 3
Al b u mi n -t o-cre ati ni ne 
r ati o ( A C R)
< 3 0 m g/ g
O R     
< 3 m g/ m m ol 
3 0 t o 3 0 0 m g/ g
O R 
3 t o 3 0 m g/ m m ol
> 3 0 0 m g/ g 
O R 
> 3 0 m g/ m m ol
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 1
1 0. 7. A p pe n di x 7 : 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 d 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 yst 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 2

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 yt 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 Fi 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 ds 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 y t 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 cli 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-
incl 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 3
1 0. 8. A p pe n di x 8 : 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 nc o mita nt me dicati o ns 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 d y. 
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 di cati 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 t he 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 nt s 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 K 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 nar r 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 . 
Sis u nat o vir als o ma y  be a n i n hi bit or of O C T 1 a n d M A T E 1 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 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 d uct 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. 
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 y t 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
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 4
C Y P 3 A I n hi bit ors
M o der ate
Str o n g
Er y t hr o myci 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 y ci 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
Alfe nta nil
L o vastati n
Alfe 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
Fe nta n yl
Se nsiti ve M A T E 1 S u bstr ates
Metf or mi n
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
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 5
P- g p I n hi bit ors
P- g p I n d ucers
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
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 y t hr o myci 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
Se nsiti ve O C T S u bstr ates
I mati ni b 
N ot a n all -i ncl usi ve list.
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 6
1 0. 9. A p pe n di x 9 : 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
% C V
c oefficie nt of variati o n as perce nta ge
A 1 t o A 3
al b u mi n uria ( K DI G O al b u mi n uria se verit y sta n dar dizati o n)
A bs
a bs ol ute
A C R
al b u mi n-t o-creati ni ne rati o
A D L
acti vit y/acti vities of daily li vi n g
A D M E
a bs or pti o n, distri b uti o n , meta b olis m , a n d e xcreti o n
A E
a d verse e ve nt
A KI
ac ute ki d ne y i nj ur y
A L P
al kali ne p h os p hatase
A L T
ala ni ne a mi n otra nsferase
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 1 2
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 1 2 h o urs
A U C 2 4
area u n der t he c o nce ntrati o n-ti me c ur ve fr o m ti me 0 t o 2 4 h o urs
A U C i nf
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 e xtra p olate d t o 
i nfi nite ti me
A U C last
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o t he ti me of 
t he last q ua ntifia ble c o nce ntrati o n
A U C ta u
area u n der t he c o nce ntrati o n -ti me c ur ve at stea dy state o ver t he 
d osi n g i nter val ta u
A V
atri o ve ntric ular
A x M P
a u xiliar y me dici nal pr o d uct
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
BI D
t wice a da y
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
C F R
C o de of Fe deral Re g ulati o ns
CI
c o nfi de nce i nter val
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
cleara nce
C last
t he last q ua ntifia ble c o nce ntrati o n
C last*
pre dicte d plas ma c o nce ntrati o n at t he last q ua ntifia ble ti me p oi nt 
esti mate d fr o m t he l o g-li near re gressi o n a nalys is
C L / F
a p pare nt cleara nce
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)
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 7
A b bre vi ati o n
Ter m
C -Q T
co nce ntrati o n Q T
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 Y P
c yt oc hr o me P 4 5 0
D #
D a y  #
D C T
data c ollecti o n t o ol
D DI
dr u g -dr u g i nteracti o n 
D F
dis o pr o xil f u marate
D H T
di gital healt h tec h n ol o g y
DI C
dr u g i n ca ps ule
DI CI
dr u g -i n d uce d creati ni ne i ncrease
DI KI
dr u g -i n d uce d ki d ne y i nj ur y
DI LI
dr u g -i n d uce d li ver i nj ur y
D P B
dr y  p o w der ble n d
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
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 M A
E ur o pea n Me dici nes A ge nc y
e S A E
electr o nic seri o us a d verse e ve nt
E T
earl y ter mi nati o n
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 nical Trials 
( E ur o pea n Cli nical Trials Data base)
F
f usi o n
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
G 1 t o G 5
Gra de ( K DI G O e G F R cate g or y  sta n dar dizati o n)
G C P
G o o d Cli nical Practice
G G T
ga m ma -gl uta m y l tra nsferase
GI
gastr oi ntesti nal
H 2O
water
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 8
A b bre vi ati o n
Ter m
H Bc A b
he patitis B c ore a nti b o d y
H B P
h y dr o x y p r o pyl
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
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
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 C U
i nte nsi ve care u nit
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
i n vesti gati o nal pr o d uct
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
Pr o p orti o nalit y  c o nsta nt f or Sc h wartz E q uati o ns ( ki d ne y f u ncti o n)
K DI G O
Ki d ne y  Disease I m pr o vi n g Gl o bal O utc o mes
k el
ter mi nal p hase rate c o nsta nt
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 n
M A D
m ulti ple asce n di n g d ose
M A T E
m ulti dr u g a n d t o xic c o m p o u n d e xtr usi o n pr otei n
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
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
O C T
or ga nic cati o n tra ns p orter
P C R U
Pfizer Cli nical Researc h U nit
P E
p h y sical e xa mi nati o n
P -g p
P -gl yc o pr otei n
PI C
P o w der i n Ca ps ule
P K
p har mac o ki netic(s)
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
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 9
A b bre vi ati o n
Ter m
Q 1 2 h
e ver y 1 2 h o urs
Q Tc
c orrecte d Q T i nter val
Q Tc F
Q Tc c orrecte d usi n g Fri dericia’s f or m ula
q ual
q ualitati ve
R B C
re d bl o o d cell
R S V
res pirat or y sy n c ytial vir us
S A D
si n gle asce n di n g d ose
S A E
seri o us a d verse e ve nt
S A P
Statistical A nal y sis Pla n
Screat
ser u m creati ni ne 
Sc y s
ser u m c ystati n C
S m P C
S u m mar y  of Pr o d uct C haracteristics
S o A
sc he d ule of acti vities
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 U S A R
S us pecte d U ne x pecte d Seri o us A d verse Reacti o n
t½
ter mi nal p hase half-life
T bili
t otal bilir u bi n
T E A E
treat me nt-e mer ge nt a d verse e ve nt
T H C
tetra hy dr oca n na bi n ol
T ma x
ti me t o reac h Cma x
U L N
u p per li mit of n or mal
U R TI
u p per res pirat or y  tract i nfecti o n
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
V z/ F 
a p pare nt v ol u me of distri b uti o n f or e xtra vasc ular d osi n g
W B C
w hite bl o o d cell
W G T
Wet Gra n ulati o n Ta blet
W O C B P
w o ma n/ w o me n of c hil d beari n g p ote ntial
0 9 0 1 7 7 e 1 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)

Sis u nat o vir (P F -0 7 9 2 3 5 6 8 )
Pr ot oc ol C 5 2 4 1 0 1 3
Pr ot oc ol A me n d me nt 1 , 0 9 N o ve m ber 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 0 0
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 I nfecti 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 sy nc yt ial vir us i n 
c hil dre n y o u n ger t ha n 5 ye ars i n 2 0 1 9: a s ys te matic a nalys is. La ncet. 
2 0 2 2; 3 9 9( 1 0 3 4 0): 2 0 4 7 -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 ytial 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):e 2 0 1 9 3 6 1 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 - 8 5.
5.
Ki m L , R ha B, A bra ms o n J S, et al. I de 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- 2 5.
6.
S Y N A GI S ( pali viz u ma b). U S Prescri pti o n I nf or mati o n ( U S PI ); Mar 20 1 4, 
Gait hers b ur g, M D: Me d I m m u ne, L L C. A vaila ble fr o m: 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 1 4/ 1 0 3 7 7 0s 5 1 8 5l bl. p df. 
Accesse d: 2 3 Mar 2 0 2 3.
7.
S Y N A GI S ( pali viz u ma b) S m P C. E P A R pr o d uct i nf or mati o n: E M A. A vaila ble fr o m: 
htt ps:// w w w.e ma.e ur o pa .e u/e n/ d oc u me nts/ pr o d uct-i nf or mati o n/s yna gis -e par-pr o d uct -
i nf or mati o n _e n. p df. Accesse d: 2 3 Mar 2 0 2 3.
8.
B E Y F O R T U S ( nirse vi ma b) S m P C. E P A R pr o d uct i nf or mati o n: E M A. A vaila ble 
fr o m: htt ps:// w w w.e ma.e ur o pa.e u/e n/ d oc u me nts/ pr o d uct-i nf or mati o n/ be yf ort us-e par -
pr o d uct -i nf or mati o n _e n. p df. Accesse d: 1 3 A pr 2 0 2 3.
9.
I n ker L, E nea nya N, C ores h J, et al. Ne w Creati ni ne- a n d C ys tati 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 9f 2 4ff 3 5\ A p pr o v e d\ A p pr o v e d O n: 1 0- N o v- 2 0 2 3 1 4: 5 2 ( G M T)