Clinical trial NCT05878522
Conditions: Healthy
Keywords: Healthy volunteers
Sponsor: Pfizer
Start date: 2023-05-15; Completion date: 2023-10-30
Enrollment: 43 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of the study is to investigate the effects of multiple oral doses of sisunatovir on QTc Interval.

This study is seeking participants who:

* are male or female of 18 years of age or older
* are examined to be healthy All participants will receive Treatment A, B, and C in a randomized order based on 6 possible sequences. All treatments will be taken by mouth. Participants assigned to treatment A will receive 5 oral doses of sisunatovir administered Q12 hours over 3 days in a fed state. Participants assigned to treatment B will receive 5 oral doses of matching placebo administered Q12 hours over 3 days in a fed state. Participants assigned to treatment C will receive 4 oral doses of placebo administered Q12 hours for 2 days followed by a single dose of 400 mg moxifloxacin on the morning of Day 3.

All participants will remain in the study clinic for 4 days for each treatment, for safety review, laboratory collections, and to assess how the study medicine affects QTc intervals.

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 examined to see whether they are fit for the study. During this period, the participant's medical history and past and current medications will be reviewed. A series of tests will also be performed to see if they are good to be selected for the study. If the participant meets all required criteria and are interested in continuing, the participant will be brought into the study clinic to stay overnight for 4 days for each treatment. On day 4, the participant will be discharged. About 28 to 35 days after discharge 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 conclude the study.

Detailed description:

Arms: arm 1: 6 capsules of sisunatovir administered Q12 hours for 5 doses arm 2: 6 capsules of placebo administered Q12 hours for 5 doses arm 3: 6 capsules of placebo administered Q12 hours for 4 doses, followed by a single tablet of moxifloxacin arm 4: 7 capsules of sisunatovir administered Q12 hours for 5 doses
Interventions: intervention 1: sisunatovir intervention 2: placebo intervention 3: moxifloxacin intervention 4: sisunatovir
Intervention descriptions: intervention 1: 6 capsules administered Q12 hours for 5 doses intervention 2: 6 capsules administered Q12 hours for 5 doses intervention 3: 6 capsules of placebo administered Q12 hours for 4 doses, followed by a single tablet of moxifloxacin intervention 4: 7 capsules administered Q12 hours for 5 doses

Protocol documents:
Prot_000.pdf: 
P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 1
Title P a ge
A P H A S E 1, R A N D O MI Z E D, D O U B L E -B LI N D, S P O N S O R -O P E N, P L A C E B O - A N D 
P O SI TI V E - C O N T R O L L E D C R O S S O V E R S T U D Y T O I N V E S TI G A T E T H E 
E F F E C T O F M U L TI P L E D O S E S O F SI S U N A T O VI R O N Q T C I N T E R V A L I N 
H E A L T H Y A D U L T P A R TI CI P A N T S
St u d y I nter ve nti o n N u m ber :
P F - 0 7 9 2 3 5 6 8
St u d y I nter ve nti o n N a me:
Sis u nat o vir
U S I N D N u m ber:
1 4 3 4 7 9
[E u dr a C T /E U C T] N u m ber:
N A
Cli nic al Tri als. g o v I D:  
N A
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N A
Pr ot oc ol N u m ber:
C 5 2 4 1 0 1 5
P h ase:
1
S p o ns or Le g al A d dress:
Pfizer I nc.
6 6 H u ds o n B o ule var d East
Ne w Y or k, N Y 1 0 0 0 1
Brief Title: A St u d y  t o I n vesti gate t he Effects of Sis u nat o vir o n Q Tc I nter val i n Healt h y 
A d ult Partici pa nts.
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer. E xce pt as 
ot her wise a gree d t o i n writi n g, b y acce pti n g or re vie wi n g t hese d oc u me nt s, yo u a gree t o h ol d t his 
i nf or mati o n i n c o nfi de nce a n d n ot c o p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w ) or 
use it f or u na ut h orize d p ur p oses. I n t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer 
m ust be pr o m ptl y n otifie d.
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)


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


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


P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 4
Secti o n # a n d N a m e
Descri pti o n of C h a n ge
Brief R ati o n ale
1 0. 4. 2 Fe male 
Partici pa nt Re pr o d ucti ve 
I ncl usi o n Criteria
Clarifie d t hat W O C B P a gree to use 
c o ntrace pti o n f or at least 2 8 da ys after last d ose 
of st u d y i nter ve nti o n
T he n u m ber of da ys was 
pre vi o usl y o mitte d 
1 1 Refere nces
A d de d 2 ref ere nces relate d t o Q Tc F pea k dela ys 
w he n m o xifl o xaci n is a d mi nistere d u n der fe d 
c o n diti o ns
Res p o nse t o F D A fee d bac k
T A B L E O F C O N T E N T S
LI S T O F T A B L E S ...................................................................................................................1 0
1. P R O T O C O L  S U M M A R Y...................................................................................................1 1
1. 1. S y n o psis ..................................................................................................................1 1
1. 2. Sc he ma ....................................................................................................................1 8
1. 3. Sc he d ule of Acti vities .............................................................................................1 9
2. I N T R O D U C TI O N ...............................................................................................................2 3
2. 1. St u d y  Rati o nale.......................................................................................................2 3
2. 2. Bac k gr o u n d .............................................................................................................2 3
2. 2. 1. N o ncli nical P har mac ol o g y ..........................................................................2 4
2. 2. 2. N o ncli nical P har mac o ki netics a n d Meta b olis m ......................................... 2 5
2. 2. 3. N o ncli nical Safet y ...................................................................................... 2 6
2. 2. 4. Cli nical O ver vie w .......................................................................................2 7
2. 3. Be nefit/ Ris k Assess me nt .........................................................................................3 0
2. 3. 1. Ris k Assess me nt......................................................................................... 3 1
2. 3. 2. Be nefit Assess me nt .....................................................................................3 4
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................3 4
3. O BJ E C TI V E S A N D E N D P OI N T S .....................................................................................3 4
4. S T U D Y D E SI G N .................................................................................................................3 4
4. 1. O verall Desi g n .........................................................................................................3 4
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n.....................................................................3 5
4. 2. 1. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts .........................................3 7
4. 3. J ustificati o n f or D ose ..............................................................................................3 7
4. 4. E n d of St u d y  Defi niti o n ..........................................................................................3 9
5. S T U D Y P O P U L A T I ON................................ ......................................................................3 9
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P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 5
5. 1. I ncl usi o n Criteria .....................................................................................................3 9
5. 2. E xcl usi o n Criteria ....................................................................................................4 0
5. 3. L ifest yle C o nsi derati o ns..........................................................................................4 2
5. 3. 1. C o ntrace pti o n ..............................................................................................4 2
5. 3. 2. Meals a n d Dietar y  Restricti o ns...................................................................4 3
5. 3. 3. Caffei ne, Alc o h ol, a n d T o bacc o .................................................................4 4
5. 3. 4. Acti vit y .......................................................................................................4 4
5. 4. Scree n Fail ures ........................................................................................................4 4
6. S T U D Y I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y .................................4 4
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................4 5
6. 1. 1. A d mi nistrati o n ............................................................................................4 6
6. 2. Pre parati o n, Ha n dli n g, St ora ge, a n d Acc o u nta bilit y ...............................................4 6
6. 2. 1. U p o n i de ntificati o n of a pr o d uct c o m plai nt, n otif y  t he s p o ns or wit hi n 
1 b usi ness da y  of disc o ver y. Pre parati o n a n d Dis pe nsi n g................................4 7
6. 3. Assi g n me nt t o St u d y I nter ve nti o n ...........................................................................4 7
6. 4. Bli n di n g................................ ...................................................................................4 8
6. 4. 1. Bli n di n g of Partici pa nts ..............................................................................4 8
6. 4. 2. Bli n di n g of Site Pers o n nel ..........................................................................4 8
6. 4. 3. Bli n di n g of t he S p o ns or.............................................................................. 4 8
6. 4. 4. Brea ki n g t he Bli n d ......................................................................................4 8
6. 5. St u d y  Inter ve nti o n C o m plia nce ...............................................................................4 9
6. 6. D ose M o dificati o n ...................................................................................................4 9
6. 7. C o nti n ue d Access t o St u d y  Inter ve nti o n After t he E n d of t he St u d y ......................4 9
6. 8. Treat me nt of O ver d ose................................ ............................................................4 9
6. 9. Pri or a n d C o nc o mita nt T hera p y................................ ..............................................5 0
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L ...........................................................................5 0
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n ....................................................................5 0
7. 2. Partici pa nt Disc o nti n uati o n/ Wit h dra wal Fr o m t he St u d y .......................................5 1
7. 2. 1. Wit h dra wal of C o nse nt ...............................................................................5 2
7. 3. L ost t o F oll o w - u p....................................................................................................5 2
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S................................ ...............................5 2
8. 1. A d mi nistrati ve a n d Baseli ne Pr oce d ures .................................................................5 2
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)


P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
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8. 1. 1. Baseli ne Pr oce d ures ....................................................................................5 4
8. 2. Efficac y  Assess me nts ..............................................................................................5 4
8. 3. Safet y Assess me nts .................................................................................................5 4
8. 3. 1. P h y sical E xa mi nati o ns ................................................................................5 4
8. 3. 2. Vital Si g ns ..................................................................................................5 4
8. 3. 2. 1. Bl o o d Press ure a n d P ulse Rate ..................................................5 4
8. 3. 3. Electr ocar di o gra ms..................................................................................... 5 5
8. 3. 4. Cli nical Safet y  La b orat or y Assess me nts....................................................5 7
8. 3. 5. C O VI D - 1 9 S pecific Assess me nts...............................................................5 7
8. 3. 6. Pre g na nc y  Testi n g ......................................................................................5 7
8. 4. A d verse E ve nts, Seri o us A d verse E ve nts, a n d Ot her Safet y Re p orti n g .................5 8
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y  f or C ollecti n g A E a n d S A E I nf or mati o n.......5 8
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer Safet y...............................................5 9
8. 4. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F................... 5 9
8. 4. 2. Met h o d of Detecti n g A Es a n d S A Es ..........................................................5 9
8. 4. 3. F oll o w- U p of A Es a n d S A Es ......................................................................5 9
8. 4. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................6 0
8. 4. 5. E n vir o n me ntal E x p os ure, E x p os ure D uri n g Pre g na nc y  or 
Breastfee di n g, a n d Occ u pati o nal E x p os ure .....................................................6 0
8. 4. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................6 0
8. 4. 5. 2. E x p os ure D u ri n g Breastfee di n g ................................................6 2
8. 4. 5. 3. Occ u pati o nal E x p os ure .............................................................6 3
8. 4. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................6 3
8. 4. 7. Disease -Relate d E ve nts a n d/ or Disease - Relate d O utc o mes N ot 
Q ualif yi n g as A Es or S A Es ..............................................................................6 3
8. 4. 8. A d verse E ve nts of S pecial I nterest............................................................. 6 3
8. 4. 8. 1. Lac k of Eff icac y........................................................................6 3
8. 4. 9. Me dical De vice Deficie ncies ......................................................................6 3
8. 4. 1 0. Me dicati o n Err ors .....................................................................................6 3
8. 5. P har mac o ki netics ....................................................................................................6 4
8. 6. G e netics ...................................................................................................................6 5
8. 6. 1. S pecifie d Ge netics ......................................................................................6 5
8. 7. Bi o mar kers ..............................................................................................................6 5
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P F -0 7 9 2 3 5 6 8 - Sis u nat o vir
Pr ot oc ol C 5 2 4 1 0 1 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 1 Ma y 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical P har mac ol o g y Pr ot oc ol Te m plate ( 0 1 A pril 2 0 2 2)
Pa ge 7
8. 8. I m m u n o ge nicit y Assess me nts .................................................................................6 5
8. 9. Healt h Ec o n o mics ...................................................................................................6 5
9. S T A TI S TI C A L C O N SI D E R A T I O N S ................................................................................6 5
9. 1. Statistical H y p ot hesis ..............................................................................................6 6
9. 1. 1. Pri mar y  E n d p oi nt........................................................................................6 6
9. 1. 2. Assa y  Se nsiti vit y ........................................................................................6 6
9. 2. A nal y sis Sets ...........................................................................................................6 6
9. 3. Statistical A nal y ses .................................................................................................6 7
9. 3. 1. Ge neral C o nsi derati o ns ...............................................................................6 7
9. 3. 1. 1. Deri vati o n of E C G Para meters Pri or t o A nal y ses .....................6 8
9. 3. 1. 2. E C G Data S u m maries ...............................................................6 8
9. 3. 2. Pri mar y  E n d p oi nt A nal ysis .........................................................................6 9
9. 3. 3. Sec o n dar y  E n d p oi nts A nal ysis ...................................................................6 9
9. 3. 4. Safet y a nal ys es ............................................................................................7 0
9. 3. 5. E x pl orat or y  E n d p oi nts A nal ysis .................................................................7 0
9. 4. I nteri m A nal ys es .....................................................................................................7 0
9. 5. Sa m ple Size Deter mi nati o n................................ .....................................................7 0
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S................................ ..........................................................................7 2
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns...............7 2
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................7 2
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P .........................................................................7 2
1 0. 1. 2. I nf or me d C o nse nt Pr ocess ........................................................................7 3
1 0. 1. 3. Data Pr otecti o n .........................................................................................7 4
1 0. 1. 4. C o m mittees Str uct ure ...............................................................................7 4
1 0. 1. 4. 1. Data M o nit ori n g C o m mittee ...................................................7 4
1 0. 1. 5. Disse mi nati o n of Cli nical St u d y  Data ......................................................7 4
1 0. 1. 6. Data Q ualit y Ass ura nce ............................................................................7 5
1 0. 1. 7. S o urce D oc u me nts ....................................................................................7 7
1 0. 1 . 8. Use of Me dical Rec or ds............................................................................7 7
1 0. 1. 9. St u d y  a n d Site Start a n d Cl os ure ..............................................................7 8
1 0. 1. 1 0. P u blicati o n P olic y ...................................................................................7 8
0 9 0 1 7 7 e 1 9 d 5 8 2 a 6 a\ A p pr o v e d\ A p pr o v e d O n: 0 3- M a y- 2 0 2 3 1 2: 1 6 ( G M T)


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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

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