Conditions: Healthy
Keywords: Healthy Volunteers
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 25
Healthy volunteers: yes

Brief summary:
The purpose of this study is to learn how different preparations of sisunatovir are taken up into the blood when taken on an empty stomach or with a meal in healthy adults.

This study has two Parts and is seeking participants who:

\- are healthy males or females of 18 years of age or older.

Part 1:

All participants will receive treatments: A, B, and C. The participants will be assigned to take medicines A, B or C by chance, like drawing names out of a hat.

All treatments will be taken by mouth.

* Participants assigned to treatment A will take four capsules of sisunatovir on empty stomach.
* Participants assigned to treatment B will take two sisunatovir tablets on empty stomach.
* Participants assigned to treatment C will take two sisunatovir tablets with a high-fat meal.

Part 2:

All participants will receive treatments: B and D. The participants will be assigned to take medicines B and D by chance, like drawing names out of a hat.

All treatments will be taken by mouth.

* Participants assigned to treatment B will take two sisunatovir tablets on empty stomach.
* Participants assigned to treatment D will take two sisunatovir tablets with a low-fat meal.

The participants will be in the study clinic for 10 days in Part 1 and 7 days in Part 2, for:

* safety checks,
* sample collection for lab tests,
* understanding how different preparations of sisunatovir are taken up into the blood when taken on an empty stomach or with a meal.

All participants selected in the study will be required to go through a screening period up to 28 days. A screening period is the time during which a few participants are tested to see whether they are fit for the study. The participants can join the study only if they are tested be fit and are interested to take part in the study.

The participants will be allowed to go home on Day 10 during Part 1, and on Day 7 during Part 2. About 28 to 35 days after being sent home following the final treatment, the participant will be contacted for a follow up visit either in person or by telephone. This is to check up on how the participant is doing and to end the study.

Detailed description:

Arms:
arm 1: 4 capsules of sisunatovir in fasted state arm 2: 2 tablets of sisunatovir in fasted state arm 3: 2 tablets of sisunatovir with a high-fat meal arm 4: 2 tablets of sisunatovir in fasted sate arm 5: 2 tablets of sisunatovir with a low-fat meal

Interventions: intervention 1: sisunatovir
Intervention descriptions: intervention 1: Administered as either capsules in fasted state or tablet in fasted or fed state.

Protocol document:
Prot_000.pdf: 
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)

SAP_001.pdf: 
Protocol C5241013 (PF-07923568) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
DMB02-GSOP-RF02 8.0 Statistical Analysis Plan Template
TMF Doc ID: 98.03
Page 1 of 17
Protocol C5241013
A Phase 1, Randomized, Open-Label, Two-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
Statistical Analysis Plan 
(SAP)
Version:
2
Date:
30 Nov 2023
090177e19f6acbd9\Approved\Approved On: 11-Dec-2023 02:33 (GMT)


Protocol C5241013 (PF-07923568) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
DMB02-GSOP-RF02 8.0 Statistical Analysis Plan Template
TMF Doc ID: 98.03
Page 2 of 17
TABLE OF CONTENTS
LIST OF TABLES..................................................................................................................3
APPENDICES.......................................................................................................................3
1. VERSION HISTORY .........................................................................................................4
2. INTRODUCTION...............................................................................................................4
2.1. Modifications to the Analysis Plan Described in the Protocol.................................4
2.2. Study Objectives, Endpoints, and Estimands ........................................................4
2.3. Study Design.........................................................................................................5
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND CONVENTIONS ..........6
3.1. Primary Endpoints.................................................................................................7
3.2. Secondary Endpoints ............................................................................................7
3.2.1. Food Effect PK Data .................................................................................7
3.2.2. Safety Endpoints.......................................................................................7
3.2.2.1. Adverse Events........................................................................8
3.2.2.2. Laboratory Data .......................................................................8
3.2.2.3. Vital Signs................................................................................8
3.2.2.4. Electrocardiograms ..................................................................8
3.3. Other Safety Endpoints .........................................................................................8
3.4. Exploratory Endpoints ...........................................................................................8
3.5. Baseline Variables ................................................................................................9
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) .......................................................9
5. GENERAL METHODOLOGY AND CONVENTIONS.........................................................9
5.1. Hypotheses and Decision Rules............................................................................9
5.2. General Methods...................................................................................................9
5.2.1. Analyses for Binary/Categorical Endpoints................................................9
5.2.2. Analyses for Continuous Endpoints.........................................................10
5.3. Methods to Manage Missing Data.......................................................................10
5.3.1. Pharmacokinetic Data.............................................................................10
5.3.2. Safety Data.............................................................................................11
6. ANALYSES AND SUMMARIES ......................................................................................11
6.1. Primary Endpoints...............................................................................................12
6.2. Secondary Endpoints ..........................................................................................12
6.2.1. Food Effect PK Data ...............................................................................12
6.2.2. Safety Endpoints.....................................................................................13
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Protocol C5241013 (PF-07923568) Statistical Analysis Plan
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6.2.2.1. Adverse Events......................................................................13
6.2.2.2. Laboratory Data .....................................................................13
6.2.2.3. Vital Signs..............................................................................13
6.2.2.4. Electrocardiograms ................................................................13
6.3. Other Safety Summaries and Analyses Endpoint(s)............................................13
6.4. Exploratory Endpoints .........................................................................................14
6.5. Subset Analyses .................................................................................................14
6.6. Baseline and Other Summaries and Analyses ....................................................14
6.6.1. Demographic Summaries........................................................................14
6.6.2. Study Conduct and Participant Disposition..............................................14
6.6.3. Study Treatment Exposure .....................................................................14
6.6.4. Concomitant Medications and Nondrug Treatments................................14
7. INTERIM ANALYSES......................................................................................................14
APPENDICES.....................................................................................................................15
LIST OF TABLES
Table 1.  Summary of Changes.............................................................................................4
Table 2.  Part 1 Treatment Sequence....................................................................................6
Table 3.  Part 2 Treatment Sequence....................................................................................6
Table 4.  Plasma PK Parameters ..........................................................................................7
Table 5.  PK Parameters to be Summarized Descriptively by Treatment.............................12
APPENDICES
Appendix 1. SAS Code for Analyses ...................................................................................15
Appendix 2. List of Abbreviations ........................................................................................16
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Protocol C5241013 (PF-07923568) Statistical Analysis Plan
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NOTE: Italicized text within this document has been taken verbatim from the Protocol.
1. VERSION HISTORY
Table 1.  Summary of Changes
Version/
Date
Associated 
Protocol 
Amendment
Rationale
Specific Changes
1 /
02 Aug 2023
Original 
07 Jun 2023
N/A
N/A
2 /
30 Nov 2023
Amendment 1
09 Nov 2023
Addition of Part 2 for the 
evaluation of a low-fat meal 
on sisunatovir exposure 
with the WGT formulation
Added Part 2 objective and endpoints 
in Section 2.2.
Added Part 2 study design in Section 
2.3.
Added Part 2 endpoints in Section 
3.2.1.
Added analysis of Part 2 endpoints in 
Section 6.2.1.
Added sample codes for Part 2 
endpoints analysis in Appendix 1.
2. INTRODUCTION
Sisunatovir (PF-07923568, formerly RV521) is an orally administered 
 
 for the treatment of adult and pediatric 
patients with RSV.
The purpose of the study is to assess the PK, safety, and tolerability of a single oral dose of 
2 different formulations of sisunatovir when administered under fasting conditions. The oral 
PK of a new WGT formulation potentially to be used in future clinical studies will be 
compared with that of PIC formulation used in completed and ongoing clinical studies. 
Additionally, the high- and low-fat food effects on the oral PK of the new WGT formulation 
will be evaluated.
This SAP provides the detailed methodology for summary and statistical analyses of the 
data collected in Study C5241013.  
2.1. Modifications to the Analysis Plan Described in the Protocol
None.
2.2. Study Objectives, Endpoints, and Estimands
The following are the objectives and endpoints in this study. Estimand framework will not be 
applied to this Phase 1 study in healthy participants.
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Protocol C5241013 (PF-07923568) Statistical Analysis Plan
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Objectives
Endpoints
Primary: 
Primary: 
To determine the relative biovailability of 
sisunatovir following a single oral dose of 
 mg as PIC vs WGT in a fasted state
AUClast, AUCinf (if data permit*), and Cmax of 
PIC vs WGT
Secondary: 
Secondary: 
To determine the effect of a high-fat meal 
on the relative biovailability of sisunatovir 
following a single oral dose of 
 mg as 
WGT
To determine the effect of a low-fat meal
on the relative biovailability of 
sisunatovir following a single oral dose 
of 
 mg as WGT
To characterize the safety and tolerability
following a single oral dose of 
 mg of 
sisunatovir as PIC or WGT in a fasted state, 
or as WGT in a fed state
AUClast, AUCinf (if data permit*), and Cmax of 
WGT under fasted vs with a high-fat meal
AUClast, AUCinf (if data permit*), and Cmax
of WGT under fasted vs with a low-fat 
meal
Assessment of TEAEs, clinical laboratory 
abnormalities, vital signs, and 12-lead ECGs
Tertiary/Exploratory: 
Tertiary/Exploratory:
To determine additional PK parameters of 
sisunatovir following a single oral dose of 
 mg as PIC or WGT in a fasted state, or 
as WGT in a fed state
Additional plasma PK parameters:
o
CL/F and Vz/F as data permit
o
Tmax
o
t½, as data permit
*Should it be deemed that too few AUCinf estimates (eg, less than 10 for a single dose) are obtained from the 
evaluable participants, AUClast may be selected as the primary/secondary endpoint for CSR reporting 
(otherwise AUClast will be an exploratory endpoint).
2.3. Study Design
This is a Phase 1, randomized, open-label, 2-part crossover study to evaluate the PK, food 
effect, safety, and tolerability of sisunatovir 
 mg single dose administered as PIC or WGT 
under fasted conditions, or as WGT with food.
Part 1
Participants will be admitted to the CRU on Day -1 to undergo baseline procedures. Over 
the first 2 periods, all participants are planned to receive 1 dose of (A) sisunatovir 
 mg as 
PIC and 1 dose of (B) sisunatovir 
 mg as WGT in a fasted state. All participants in Period 
3 will receive 1 dose of (C) sisunatovir 
 mg as WGT with a high-fat meal (Table 2). There 
is an at least 72-hour washout period between the dose of 2 adjacent periods.
Part 1 consists of an initial screening period of up to 28 days (while allowing for the return 
and review of all results, including laboratory tests), a 10-day inpatient stay at the CRU 
which includes 3 periods, and a follow-up contact that will occur 28-35 days after the last 
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administration of sisunatovir. For individual participants, the total duration of participation 
from the screening visit to the follow-up visit will range from approximately 6 weeks 
(minimum) to approximately 10 weeks (maximum).
Approximately 12 participants will be randomized into 2 sequences with 6 participants each.
For each sequence, participants will receive study interventions in a pre-specified manner 
as listed in Table 2.
Table 2.  Part 1 Treatment Sequence
Period 1
Period 2
Period 3
Sequence 1 (N=6)
A
B
C
Sequence 2 (N=6)
B
A
C
All study interventions will be administered as a single dose of sisunatovir 
 mg as PIC or WGT.
A= PIC under fasted condition; B = WGT under fasted condition; C= WGT with a high-fat meal.
Part 2
Participants will be admitted to the CRU on Day -1 to undergo baseline procedures. All 
participants are planned to receive 1 dose of (B) sisunatovir 
 mg as WGT in a fasted 
state and 1 dose of (D) sisunatovir 
 mg as WGT with a low-fat meal. There is an at least 
72-hour washout period between the dose of the 2 periods. Participants who have 
completed Part 1 are eligible to participate in Part 2.
Table 3.  Part 2 Treatment Sequence
Period 1
Period 2
Sequence 1 (N=6)
B
D
Sequence 2 (N=6)
D
B
All study interventions will be administered as a single dose of 
-mg sisunatovir as WGT.
B = WGT under fasted condition; D= WGT with a low-fat meal.
Participants who discontinue from the study for non-safety reasons may be replaced at the 
sponsor’s discretion in collaboration with the investigator.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND CONVENTIONS
PK parameters for sisunatovir will be derived from the concentration-time profiles using
noncompartmental methods as data permit. The PK parameters to be assessed in this 
study, their definition, and method of determination are outlined in Table 4. In all cases, 
actual PK sampling times will be used in the derivation of PK parameters when available. In 
the case that actual PK sampling times are not available, nominal PK sampling time will be 
used in the derivation of PK parameters.
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Table 4.  Plasma PK Parameters 
Parameter
Definition
Method of Determination
AUClast
Area under the plasma concentration-time 
profile from time 0 to the time of the last 
quantifiable concentration (Clast)
Linear/Log trapezoidal method.
AUCinfa
Area under the concentration-time profile 
from time 0 extrapolated to infinite time
AUClast + (Clast*/kel),
where Clast* is the predicted plasma 
concentration at the last quantifiable 
time point estimated from the log-
linear regression analysis.
Cmax
Maximum observed plasma concentration
Observed directly from data.
Tmax
Time to reach Cmax
Observed directly from data as time 
of first occurrence
t½a
Terminal half-life
Loge(2)/kel,
where kel is the terminal phase rate 
constant calculated by a linear 
regression of the log-linear 
concentration-time curve. Only 
those data points judged to describe 
the terminal log-linear decline will be 
used in the regression.
CL/Fa
Apparent clearance
Dose/AUCinf.
Vz/Fa
Apparent volume of distribution
Dose/(AUCinf • kel).
a. As data permits.
3.1. Primary Endpoints
The primary endpoints are the plasma AUClast, AUCinf (if data permit) and Cmax of sisunatovir
 mg as PIC or WGT in a fasted state. Adjusted geometric mean ratios of AUClast, AUCinf
and Cmax will be derived with Treatment B (sisunatovir
 mg WGT under fasted condition)
as the test treatment and Treatment A (sisunatovir
 mg PIC under fasted condition) as 
the reference treatment.
3.2. Secondary Endpoints
3.2.1. Food Effect PK Data
Plasma AUClast, AUCinf (if data permit) and Cmax of sisunatovir
 mg as WGT with a high-
fat meal. Adjusted geometric mean ratios of AUClast, AUCinf and Cmax with Treatment C 
(sisunatovir
mg WGT with a high-fat meal) as the test treatment and Treatment B 
(sisunatovir
mg WGT under fasted condition) as the reference treatment.
Plasma AUClast, AUCinf (if data permit) and Cmax of sisunatovir
 mg as WGT with a low-fat 
meal. Adjusted geometric mean ratios of AUClast, AUCinf and Cmax with Treatment D 
(sisunatovir
mg WGT with a low-fat meal) as the test treatment and Treatment B 
(sisunatovir
mg WGT under fasted condition) as the reference treatment.
3.2.2. Safety Endpoints
The following data are considered in standard safety summaries (see protocol for collection
days, baseline assessment, and list of parameters):

TEAEs
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
laboratory data

vital signs data

electrocardiogram (ECG) results
3.2.2.1. Adverse Events
Any adverse events occurring following start of treatment will be considered as treatment 
emergent adverse event (TEAE). Events that occur during follow-up within the lag time of up 
to 35 days after the last sisunatovir dose will be counted as treatment emergent and 
attributed to the last treatment taken. Events that occur during the washout period will be 
counted as treatment emergent and attributed to the previous treatment taken. The time 
period for collecting AEs (“active collection period”) for each participant begins from the time 
the participant provides informed consent.
3.2.2.2. Laboratory Data
Safety laboratory tests will be performed as described in the protocol.
For Period 1, the baseline measurement is the last predose measurement on Day -1. For
Periods 2 and 3, the baseline measurement is the last predose measurement on Day 1 of 
each period. Changes from baseline will be defined as the change between the postdose 
and baseline measurements.
3.2.2.3. Vital Signs
Supine blood pressure (BP) and pulse rate will be measured at times specified in the SoA 
given in the protocol.
For each period, the baseline measurement is the last predose measurement on Day 1. 
Changes from baseline will be defined as the change between the postdose and baseline 
measurements.
3.2.2.4. Electrocardiograms
QT interval, QTcF, PR, QRS and heart rate (HR) will be recorded at each assessment time 
indicated in the SoA given in the protocol. QTcF will be derived using Fridericia’s heart rate 
correction formula:
QTcF = QT / (RR)^(1/3) where RR = 60/HR (if not provided)
For each period, the baseline measurement is the last predose measurement on Day 1. 
Changes from baseline will be defined as the change between the postdose and baseline 
measurements.
3.3. Other Safety Endpoints
None.
3.4. Exploratory Endpoints
Exploratory endpoints are additional plasma PK parameters of sisunatovir (CL/F, Vz/F, Tmax, 
t1/2) as PIC or WGT in a fasted state, or as WGT in a fed state.
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3.5. Baseline Variables
Baseline characteristics will be collected according to the SoA as specified in the protocol. 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to releasing the database and classifications will 
be documented per standard operating procedures.
For purposes of analysis, the following analysis sets are defined:
Participant Analysis Set
Description
Enrolled
“Enrolled” means a participant’s agreement to participate in a 
clinical study following completion of the informed consent process 
and randomization/assignment to study intervention. A participant 
will be considered enrolled if the informed consent is not 
withdrawn prior to participating in any study activity after 
screening. Potential participants who are screened for the purpose 
of determining eligibility for the study, but do not participate in the 
study, are not considered enrolled, unless otherwise specified by 
the protocol.
Evaluable
All participants randomly assigned to study intervention and who 
take at least 1 dose of study intervention.
Safety
All participants randomly assigned to study intervention and who 
take at least 1 dose of study intervention. Participants will be 
analyzed according to the product they actually received.
PK Parameter Set
All randomized participants who receive at least one dose of study 
medication and in whom at least 1 plasma PK parameter is 
calculated.
PK Concentration Set
All randomized participants who receive at least 1 dose of study 
medication and in whom at least 1 plasma concentration value is 
reported.
5. GENERAL METHODOLOGY AND CONVENTIONS
Final analysis will be performed after study participant data set release following last 
participant last visit.
5.1. Hypotheses and Decision Rules
No statistical hypothesis will be tested in this study.
5.2. General Methods
5.2.1. Analyses for Binary/Categorical Endpoints
For binary or categorical variables, number of participants, numbers and percentages of 
participants meeting the categorical criteria will be presented in accordance with the Clinical 
Data Interchange Standards Consortium and Pfizer Standards (CaPS).
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5.2.2. Analyses for Continuous Endpoints
For continuous variables, the data will be summarized using the number of participants, 
mean, median, standard deviation (SD), minimum, and maximum in accordance with the 
CaPS. For appropriate PK parameters, geometric mean and geometric coefficient of 
variation (%CV) will also be summarized.
5.3. Methods to Manage Missing Data
5.3.1. Pharmacokinetic Data
Methods to handle missing PK data are described below. 
Concentrations Below the Limit of Quantification:
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero. (In listings BLQ values will be reported as “<LLQ”, where LLQ will 
be replaced with the value for the lower limit of quantification.).
Deviations, Missing Concentrations and Anomalous Values:
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if one of the following cases is true:
1. A concentration has been collected as ND (ie, not done) or NS (ie, no sample).
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged as anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
An anomalous concentration value is one that, after verification of bioanalytical validity, is 
grossly inconsistent with other concentration data from the same individual or from other 
participants. For example, a BLQ concentration that is between quantifiable values from the 
same dose is considered as anomalous. Anomalous concentration values may be excluded 
from PK analysis at the discretion of the PK analyst or pharmacokineticist.
PK Parameters:
Actual PK sampling times will be used in the derivation of PK parameters. If a PK parameter 
cannot be derived from a participant’s concentration data, the parameter will be coded as 
NC (ie, not calculated). (Note that NC values will not be generated beyond the day that a 
participant discontinues). In summary tables, statistics will be calculated by setting NC 
values to missing; and statistics will be presented for a particular treatment with ≥3 
evaluable measurements. PK parameter analyses will not be performed for a particular 
parameter if more than 50% of the data are NC.
If an individual participant has a known biased estimate of a PK parameter (due for example 
to an unexpected event such as vomiting before all the compound is adequately absorbed 
from the gastrointestinal tract), this will be footnoted in summary tables and will not be 
included in the calculation of summary statistics or statistical analyses.
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5.3.2. Safety Data
Missing values in standard summaries of safety data will be imputed according to CaPS.
6. ANALYSES AND SUMMARIES
The plasma concentrations of sisunatovir will be listed and descriptively summarized by 
nominal PK sampling time and treatment on the PK Concentration Set. Individual 
participant and summary profiles (mean and median plots) of the plasma concentration-time 
data will be plotted by treatment using actual and nominal times, respectively. Mean and 
median profiles will be presented on both linear and semi-log scales. 
Presentations for sisunatovir concentrations will include:

A listing of all concentrations sorted by participant ID, treatment and nominal time
postdose. The concentration listing will also include the actual times. Deviations from the 
nominal time will be given in a separate listing.

A summary of concentrations by treatment and nominal time postdose, where the set of 
statistics will include n, mean, median, SD, %CV, minimum, maximum and the number 
of concentrations above the LLQ.

Median concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose by treatment (all treatments on the same plot per scale, based on the 
summary of concentrations by treatment and time postdose).

Mean concentrations time plots (on both linear and semi-log scales) against nominal
time postdose by treatment (all treatments on the same plot per scale, based on the 
summary of concentrations by treatment and time postdose).

Individual concentration time plots by treatment (on both linear and semi-log scales) 
against actual time postdose (there will be separate spaghetti plots for each treatment 
per scale).

Individual concentration time plots by participant (on both linear and semi-log scales)
against actual time postdose [there will be separate plots for each participant (containing
all treatments) per scale].
The PK parameters will be summarized descriptively by treatment group in accordance with 
Pfizer data standards on the PK Parameter Set, as data permit. Missing values will be 
handled as detailed in Section 5.3.1. Each PK parameter will be summarized by treatment 
group and will include the set of summary statistics as specified in Table 5. 
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Table 5.  PK Parameters to be Summarized Descriptively by Treatment 
Parameter
Summary Statistics
AUCinf, AUClast, Cmax, 
CL/F, Vz/F
N, arithmetic mean, median, SD, %CV, minimum, maximum, 
geometric mean and geometric %CV
Tmax
N, median, minimum, maximum
t½
N, arithmetic mean, median, SD, %CV, minimum, maximum
The following supporting data from the estimation of t½ will be listed by treatment group: the 
terminal phase rate constant (kel); goodness-of-fit statistic from the regression (r2); the 
percentage of AUCinf obtained by forward extrapolation (AUCextrap%); and the first, last, and 
number of time points used in the estimation of kel (kel,t(lo), kel,t(hi), and kel,t(n)).
6.1. Primary Endpoints
Plasma AUClast, AUCinf (if data permit) and Cmax will be summarized descriptively by 
treatment. Box and whisker plots for AUClast, AUCinf (if data permit) and Cmax will be plotted 
by treatment.
For the estimation of rBA of sisunatovir
 mg as WGT compared to sisunatovir
 mg as 
PIC in a fasted state, natural log transformed AUClast, AUCinf (if data permit) and Cmax will be 
analyzed separately using a mixed effect model with sequence (AB or BA), period and 
treatment included as fixed effects and participant nested within sequence as a random 
effect. Only data from the first 2 study periods will be used in the analysis. Estimates of the
adjusted mean differences (Test-Reference) and corresponding 90% CIs will be obtained
from the model. The adjusted mean differences and 90% CIs for the differences will be
exponentiated to provide estimates of the ratio of adjusted geometric means 
(Test/Reference) and 90% CIs for the ratios. Treatment A is the Reference treatment and 
Treatment B is the Test treatment.
Residuals from the model will be examined for normality and the presence of outliers via 
visual inspection of plots of residuals vs predicted values and normal probability plots of 
residuals but these will not be included in the CSR. If there are major deviations from 
normality or outliers then the effect of these on the conclusions will be investigated through 
alternative transformations and/or analyses excluding outliers. Justification for any 
alternative to the planned analysis will be given in the report of the study.
6.2. Secondary Endpoints
6.2.1. Food Effect PK Data
For the secondary endpoints on the assessment of high-fat food effect, natural log 
transformed AUClast, AUCinf (if data permit) and Cmax of sisunatovir will be analyzed using a 
mixed effect model with sequence and treatment as fixed effects and participant within 
sequence as a random effect. Estimates of the adjusted mean differences (Test-Reference) 
and corresponding 90% CIs will be obtained from the model. The adjusted mean differences 
and 90% CIs for the differences will be exponentiated to provide estimates of the ratio of 
adjusted geometric means (Test/Reference) and 90% CI for the ratios. Treatment B (WGT 
under fasted condition) is the Reference treatment and Treatment C (WGT with a high-fat 
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meal) is the Test treatment. Only the data from Treatments B and C will be included in the 
model.
For the secondary endpoints on the assessment of the low-fat food effect, natural log 
transformed AUClast, AUCinf (if data permit) and Cmax of sisunatovir will be analyzed using a 
mixed effect model with sequence and treatment as fixed effects and participant within 
sequence as a random effect. Estimates of the adjusted mean differences (Test-Reference) 
and corresponding 90% CIs will be obtained from the model. The adjusted mean differences 
and 90% CIs for the differences will be exponentiated to provide estimates of the ratio of 
adjusted geometric means (Test/Reference) and 90% CI for the ratios. Treatment B (WGT 
under fasted condition) is the Reference treatment and Treatment D (WGT with a low-fat 
meal) is the Test treatment. Only the data from Treatments B and D will be included in the 
model.
Residuals from the model will be examined for normality and the presence of outliers via 
visual inspection of plots of residuals vs predicted values and normal probability plots of 
residuals but these will not be included in the CSR. If there are major deviations from 
normality or outliers then the effect of these on the conclusions will be investigated through 
alternative transformations and/or analyses excluding outliers. Justification for any 
alternative to the planned analysis will be given in the report of the study.
Exploratory analyses may be performed to assess rBA of sisunatovir for participants who 
participated in both part 1 and part 2 of the study. These data will be used for internal 
exploratory purposes and will not be included in the clinical report.
6.2.2. Safety Endpoints
All safety analyses will be performed on the Safety Analysis Set.
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
6.2.2.1. Adverse Events
TEAEs will be reported in accordance with the CaPS.
Participant discontinuations due to adverse events will be detailed by treatment. Data will be 
reported in accordance with the CaPS.
6.2.2.2. Laboratory Data
Laboratory data will be listed and summarized by treatment in accordance with the CaPS.
6.2.2.3. Vital Signs
Vital sign data will be databased and available upon request.
6.2.2.4. Electrocardiograms
ECG data will be databased and available upon request.
6.3. Other Safety Summaries and Analyses Endpoint(s)
None.
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6.4. Exploratory Endpoints
Other plasma PK parameters including CL/F, Vz/F, Tmax and t1/2 will be summarized by 
treatment group and will include the set of summary statistics as specified in Table 5.
6.5. Subset Analyses
There are no planned subset analyses.
6.6. Baseline and Other Summaries and Analyses
6.6.1. Demographic Summaries
Demographic characteristics will be listed and summarized for Safety Analysis Set in 
accordance with the CaPS.
6.6.2. Study Conduct and Participant Disposition
Participants evaluation groups will show end of study participant disposition. Frequency 
counts will be supplied for participant discontinuation(s) by treatment. Data will be reported 
in accordance with the CaPS.
6.6.3. Study Treatment Exposure
Study treatment exposure will be listed.
6.6.4. Concomitant Medications and Nondrug Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be reported in the 
listings.
7. INTERIM ANALYSES
No formal interim analysis will be conducted for this study. As this is an open-label study, the 
sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating PK modeling, and/or supporting clinical 
development.
Final analysis will follow the official database release.  As this will be an open-label study, 
there is no formal unblinding of the randomization code.
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APPENDICES
Appendix 1. SAS Code for Analyses
An example of the PROC MIXED code is provided below:
For primary objective rBA (Periods 1 and 2):
proc mixed data=tab.pk;
class seq period trt participant;
model log&var=seq period trt/ ddfm=KR;
random participant(seq) /subject=participant(seq);
lsmeans trt;
estimate 'B vs A' trt -1 1  /cl alpha=0.1;
ods 'Estimates' out=est&var;
ods 'lsmeans' out=ls&var;
ods 'covparms' out=cov&var;
ods 'tests3' out=tst&var;
run;
For secondary objectives high-fat and low-fat FE:
proc mixed data=tab.pk;
class seq trt participant;
model log&var= seq trt / ddfm=KR;
random participant(seq) / subject=participant(seq);
lsmeans trt;
estimate 'C vs B' trt -1 1  /cl alpha=0.1;
ods 'Estimates' out=est&var;
ods 'lsmeans' out=ls&var;
ods 'covparms' out=cov&var;
ods 'tests3' out=tst&var;
run;
proc mixed data=tab.pk;
class seq trt participant;
model log&var= seq trt / ddfm=KR;
random participant(seq) / subject=participant(seq);
lsmeans trt;
estimate 'D vs B’ trt -1 1  /cl alpha=0.1;
ods ‘Estimates’ out=est&var;
ods ‘lsmeans’ out=ls&var;
ods ‘covparms’ out=cov&var;
ods ‘tests3’ out=tst&var;
run;
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/* Letter assignments for treatments (trt) within the estimate statement above are as 
follows
A: Single dose of sisunatovir
 mg as PIC under fasted condition;
B: Single dose of sisunatovir
 mg as WGT under fasted condition;
C: Single dose of sisunatovir
 mg as WGT with a high-fat meal.
D: Single dose of sisunatovir
 mg as WGT with a low-fat meal. */
Appendix 2. List of Abbreviations
Abbreviation
Term
%CV
coefficient of variation
AE
adverse event
AUCextrap%
the percent of AUCinf based on extrapolation
AUCinf
area under the concentration-time curve from time 0 to infinity
AUClast
area under the concentration-time curve from 0 to time of last measurable 
concentration
BLQ
below the limit of quantification
BP
blood pressure
CaPS
Clinical Data Interchange Standards Consortium and Pfizer Standards
CI
confidence interval
Clast
estimated plasma concentration at the last quantifiable time point estimated 
form the log-linear regression analysis
CL/F
apparent clearance
Cmax
maximum observed plasma concentration
CRU
clinical research unit
CSR
clinical study report
ECG
electrocardiogram
HR
heart rate
kel
the terminal phase rate constant calculated by a linear regression of the 
loglinear concentration-time curve
LLQ
lower limit of quantification
mg
milligram
ms
millisecond
N/A
not applicable
NC
not calculated
ND
not done
NS
no sample
PIC
Powder in Capsule
PK
pharmacokinetic(s)
PR
time from the beginning of the P wave to the beginning of the QRS complex
QRS
Combination of Q-, R- and S- wave on an electrocardiogram representing 
ventricular depolarization
QT
time from the start of the Q- wave to the end of T- wave, which represents 
time taken for ventricular depolarization and repolarization 
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
r2
goodness of fit statistic from the log-linear regression
rBA
relative bioavailability
RR
respiratory rate
RSV
respiratory syncytial virus
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Abbreviation
Term
SAP
statistical analysis plan
SD
standard deviation
SoA
schedule of activities
t1/2
terminal elimination half-life
TEAE
treatment emergent adverse event
Tmax
time to reach Cmax
Vz/F
apparent volume of distribution for extravascular dosing
WGT
Wet Granulation Tablet
090177e19f6acbd9\Approved\Approved On: 11-Dec-2023 02:33 (GMT)