Clinical trial NCT06003829
Conditions: Healthy
Sponsor: Pfizer
Start date: 2023-07-31; Completion date: 2023-09-20
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to learn about the tastes of different suspensions with the study medicine called PF-07923568 in healthy adult participants. In a suspension, the medicine is mixed with a liquid, usually water, in which it cannot dissolve and therefore remains intact in the form of small particles.

This study is seeking for healthy participants who:

* are aged 18 years of age or older.
* can produce a baby must agree to use a highly effective method of birth control.
* are confirmed to be healthy by some medical tests. This study can include both men and women.
* have body mass index (BMI) of 16 to 32 kg/m2 and a total body weight of more than 45 kilograms.

Participants will take sisunatovir prepared in 5 different suspensions and bitrex over two days to see if they are good to taste. Participants will answer a questionnaire after tasting each suspension. The questionnaire will be completed for each suspension. The questionnaire asks participants to test each suspension at 4 different times after tasting and spitting out the suspension. At least 60 minutes will pass between tasting each suspension.

The total planned time period of participation is around 5 to 8 weeks. This includes the screening period of up to 28 days. Followed by first administration of study medicine. Then a 3 day in-patient stay at the study clinic. It also includes a follow-up phone call that happens 28-35 days after the final taste test.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: Comparator arm 4: None arm 5: None arm 6: None
Interventions: intervention 1: Sinsunatovir intervention 2: Bitrex
Intervention descriptions: intervention 1: Single dose, to be spit out after tasting intervention 2: Single dose, to be spit out after tasting

Protocol documents:
Prot_000.pdf: 
P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1
Title P a ge
A R A N D O MI Z E D , P H A S E 1 , SI N G L E -B LI N D, M U L T I-P E RI O D S T U D Y T O 
I N V E S TI G A T E T H E P A L A T A BI LI T Y O F P F -0 7 9 2 3 5 6 8 O R A L S U S P E N SI O N I N 
DI F F E R E N T LI Q UI D V E HI C L E S 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 C T N u m ber:
2 0 2 3 - 5 0 4 9 2 4- 2 4- 0 0
Cli nic al Tri als. g o v I D: 
N ot a vaila ble
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N ot a p plica ble
Pr ot oc ol N u m ber:
C 5 2 4 1 0 1 4
P h ase:
1
S p o ns or Le g al A d dress:
Pfizer I nc.
6 6 H u ds o n B o ule var d East
Ne w Y or k, N Y 1 0 0 0 1
Brief Title: A St u d y  t o Lear n A b o ut t he Taste Pr ofiles of Differe nt S us pe nsi o ns of 
St u d y  Me dici ne Calle d P F- 0 7 9 2 3 5 6 8 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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2
D oc u me nt Hist or y
D oc u me nt
Versi o n D ate
Ori gi nal pr ot oc ol
1 9 Ma y  2 0 2 3
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3
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 .....................................................................................................................7
1. P R O T O C O L  S U M M A R Y.....................................................................................................8
1. 1. S y n o psis ....................................................................................................................8
1. 2. Sc he ma ....................................................................................................................1 4
1. 3. Sc he d ule of Acti vities .............................................................................................1 5
2. I N T R O D U C TI O N ...............................................................................................................1 7
2. 1. St u d y  Rati o nale.......................................................................................................1 7
2. 2. Bac k gr o u n d .............................................................................................................1 7
2. 2. 1. N o ncli nical P har mac ol o g y ..........................................................................1 7
2. 2. 2. N o ncli nical P har mac o ki netics a n d Meta b olis m ......................................... 1 8
2. 2. 3. N o ncli nical Safet y ...................................................................................... 1 8
2. 2. 4. Cli nical O ver vie w .......................................................................................1 9
2. 3. Be nefit/ Ris k Assess me nt................................ .........................................................2 1
2. 3. 1. Ris k Assess me nt......................................................................................... 2 3
2. 3. 2. Be nefit Assess me nt .....................................................................................2 4
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................2 4
3. O BJ E C TI V E S A N D E N D P OI N T S .....................................................................................2 4
4. S T U D Y D E SI G N .................................................................................................................2 4
4. 1. O verall Desi g n .........................................................................................................2 4
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n.....................................................................2 5
4. 2. 1. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts .........................................2 5
4. 3. J ustificati o n f or D ose ..............................................................................................2 6
4. 4. E n d of St u d y  Defi niti o n ..........................................................................................2 6
5. S T U D Y P O P U L A T I ON................................ ......................................................................2 6
5. 1. I ncl usi o n Criteria .....................................................................................................2 6
5. 2. E xcl usi o n Criteria ....................................................................................................2 7
5. 3. Li fest yle C o nsi derati o ns..........................................................................................2 9
5. 3. 1. C o ntrace pti o n ..............................................................................................2 9
5. 3. 2. Meals a n d Dietar y  Restricti o ns...................................................................3 0
5. 3. 3. Caffei ne a n d Alc o h ol.................................................................................. 3 0
5. 3. 4. Acti vit y .......................................................................................................3 0
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4
5. 4. Scree n Fail ures ........................................................................................................3 0
6. S T U D Y I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y .................................3 0
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................3 1
6. 1. 1. A d mi nistrati o n ............................................................................................3 2
6. 2. P re parati o n, Ha n dli n g, St ora ge, a n d Acc o u nta bilit y...............................................3 2
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ........................................................................3 3
6. 3. Assi g n me nt t o St u d y I nter ve nti o n ...........................................................................3 4
6. 4. Bli n di n g................................ ...................................................................................3 4
6. 4. 1. Bli n di n g of Partici pa nts ..............................................................................3 4
6. 4. 2. Bli n di n g of Site Pers o n nel ..........................................................................3 4
6. 4. 3. Bli n di n g of t he S p o ns or.............................................................................. 3 4
6. 5. St u d y  Inter ve nti o n C o m plia nce ...............................................................................3 4
6. 6. D ose M o dificati o n ...................................................................................................3 5
6. 7. C o nti n ue d Access t o St u d y  Inter ve nti o n After t he E n d of t he St u d y ......................3 5
6. 8. Treat me nt of O ver d ose................................ ............................................................3 5
6. 9. Pri or a n d C o nc o mita nt T hera p y................................ ..............................................3 5
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L ...........................................................................3 6
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n ....................................................................3 6
7. 1. 1. P ote ntial Cases of Ac ute Ki d ne y  Inj ur y .....................................................3 6
7. 1. 2. C O VI D - 1 9 ..................................................................................................3 8
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 .......................................3 8
7. 2. 1. Wit h dra wal of C o nse nt ...............................................................................3 9
7. 3. L ost t o F oll o w -U p ...................................................................................................3 9
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S................................ ...............................3 9
8. 1. A d mi nistrati ve Pr oce d ures ......................................................................................3 9
8. 1. 1. Baseli ne Pr oce d ures ....................................................................................4 0
8. 2. Efficac y  Assess me nts..............................................................................................4 0
8. 3. Safet y Assess me nts .................................................................................................4 1
8. 3. 1. P h y sical E xa mi nati o ns ................................................................................4 1
8. 3. 2. Vital Si g ns ..................................................................................................4 1
8. 3. 2. 1. Bl o o d Press ure a n d P ulse Rate ..................................................4 1
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5
8. 3. 3. Electr ocar di o gra ms..................................................................................... 4 2
8. 3. 4. Cli nical Safet y  La b orat or y Assess me nts....................................................4 2
8. 3. 5. Pre g na nc y  Testi n g ......................................................................................4 3
8. 4. A d verse E ve nts, Seri o us A d verse E ve nts, a n d Ot her Safet y Re p orti n g .................4 3
8. 4. 1. Ti me Peri o d a n d Fre q ue nc y  f or C ollecti n g A E a n d S A E I nf or mati o n.......4 4
8. 4. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ...............................................4 4
8. 4. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F................... 4 5
8. 4. 2. Met h o d of Detecti n g A Es a n d S A Es ..........................................................4 5
8. 4. 3. F oll o w -U p of A Es a n d S A Es ......................................................................4 6
8. 4. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................4 6
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 .....................................................4 6
8. 4. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................4 7
8. 4. 5. 2. E x p os ure D uri n g Breastfee di n g ................................................4 8
8. 4. 5. 3. Occ u pati o nal E x p os ure .............................................................4 9
8. 4. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................4 9
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 ..............................................................................4 9
8. 4. 8. A d verse E ve nts of S pecial I nterest............................................................. 4 9
8. 4. 8. 1. Lac k of Efficac y ........................................................................4 9
8. 4. 9. Me dical De vice Deficie ncies ......................................................................4 9
8. 4. 1 0. Me dicati o n Err ors .....................................................................................4 9
8. 5. P har mac o ki netics ....................................................................................................5 0
8. 6. Ge netics ...................................................................................................................5 0
8. 7. Bi o mar kers ..............................................................................................................5 0
8. 8. I m m u n o ge nicit y Assess me nts .................................................................................5 0
8. 9. Healt h Ec o n o mics ...................................................................................................5 0
8. 1 0. Palata bilit y  assess me nt..........................................................................................5 0
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................ 5 1
9. 1. Statistical H y p ot hesis/ H y p ot heses ..........................................................................5 1
9. 2. A nal y sis Sets ...........................................................................................................5 1
9. 3. Statistical A nal y ses .................................................................................................5 1
9. 3. 1. Ge neral C o nsi derati o ns ...............................................................................5 1
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6
9. 3. 2. Pri mar y  E n d p oi nt(s) A nalys is.....................................................................5 2
9. 3. 3. Sec o n dar y  E n d p oi nt(s) A nalys is.................................................................5 2
9. 4. I nteri m A nal ys es .....................................................................................................5 2
9. 5. Sa m ple Size Deter mi nati o n .....................................................................................5 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................................ ..........................................................................5 4
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...............5 4
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ....................................................5 4
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 .........................................................................5 4
1 0. 1. 2. I nf or me d C o nse nt Pr ocess ........................................................................5 5
1 0. 1. 3. Data Pr otecti o n .........................................................................................5 6
1 0. 1. 3. 1. Data M o nit ori n g C o m mittee ...................................................5 6
1 0. 1. 4. Disse mi nati o n of Cli nical St u d y  Data ......................................................5 6
1 0. 1. 5. Data Q ualit y Ass ura nce ............................................................................5 7
1 0. 1. 6. S o urce D oc u me nts ....................................................................................5 9
1 0. 1. 7. Use of Me dical Rec or ds ............................................................................5 9
1 0. 1. 8. St u d y  a n d Site Start a n d Cl os ure ..............................................................6 0
1 0. 1. 9. P u blicati o n P olic y..................................................................................... 6 0
1 0. 1. 1 0. S p o ns or’s Me dicall y  Q ualifie d I n di vi d ual..............................................6 1
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests.................................................................6 3
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 .....................................................................6 6
1 0. 3. 1. Defi niti o n of A E .......................................................................................6 6
1 0. 3. 2. Defi niti o n of a n S A E ................................................................................6 7
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............................................................................6 8
1 0. 3. 4. Re p orti n g of S A Es ....................................................................................7 2
1 0. 4. A p pe n di x 4: C o ntrace pti ve a n d Barrier G ui da nce ................................................7 3
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria.................................... 7 3
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria .................................7 3
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ............................................................7 4
1 0. 4. 4. C o ntrace pti o n Met h o ds .............................................................................7 5
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7
1 0. 5. A p pe n di x 5: L i ver Safet y: S u g geste d Acti o ns a n d F oll o w-U p Assess me nts .......7 7
1 0. 6. A p pe n di x 6 : Ki d ne y Safet y: M o nit ori n g G ui deli nes ............................................7 9
1 0. 6. 1. La b orat or y  Assess me nt of C ha n ge i n Ki d ne y F u ncti o n a n d 
Detecti o n of Ki d ne y  Inj ur y................................ ..............................................7 9
1 0. 6. 2. A ge -S pecific Ki d ne y  F u ncti o n Calc ulati o n Rec o m me n dati o ns...............7 9
1 0. 6. 2. 1. A d ults ( 1 8 Years a n d A b o ve) — 2 0 2 1 C K D - E PI 
E q uati o ns........................................................................................... 7 9
1 0. 6. 3. Ki d ne y  F u ncti o n Calc ulati o n T o ols..........................................................7 9
1 0. 6. 4. A d verse E ve nt Gra di n g f or Ki d ne y  Safety La b ora t or y 
A b n or malities ...................................................................................................8 0
1 0. 7. A p pe n di x 7: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n ...................................8 1
1 0. 8. A p pe n di x 8: Pr o hi bite d C o nc o mita nt Me dicati o ns T hat Ma y Res ult i n D DI .......8 3
1 0. 9. A p pe n di x 9: Oral S ol uti o n or S us pe nsi o n Palata bilit y  Q uesti o n naire..................8 6
1 0. 1 0. A p pe n di x 1 0: A b bre viati o ns ...............................................................................9 4
1 1. R E F E R E N C E S ..................................................................................................................9 8
LI S T O F T A B L E S
Ta ble 1.
Sa m ple D osi n g Sc he me ............................................................................1 4
Ta ble 2.
S t u d y Sc he d ule of Assess me nt.................................................................1 5
Ta ble 3.
C o m plete d Sis u nat o vir St u dies................................................................. 1 9
Ta ble 4.
Pr ot oc ol -Re q uire d La b orat or y  Assess me nts.............................................6 4
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
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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 Ra n d o mize d, P hase 1, Si n gle -Bli n d, M ulti -Peri o d St u d y  to I n vesti gate the 
Palata bilit y  of P F -0 7 9 2 3 5 6 8 Oral S us pe nsi o n in Differe nt L i q ui d Ve hicles in Healt h y  A d ult 
Partici pa nts
Brief Title: A St u d y  t o Lear n A b o ut the Taste Pr ofiles of Differe nt S us pe nsi o ns of St u d y  
Me dici ne Calle d P F -0 7 9 2 3 5 6 8 i n Healt h y  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 C T N u m ber:
2 0 2 3 -5 0 4 9 2 4 -2 4 -0 0
Cli nic al Tri als. g o v I D:  
N ot a vaila ble
Pe di atric I n vesti g ati o n al Pl a n N u m ber:
N ot a p plica ble
Pr ot oc ol N u m ber:
C 5 2 4 1 0 1 4
P h ase:
1
R ati o n ale :
T he p ur p ose of t he st u d y  is t o assess palata bilit y of sis un at o vir i n prese nce of differe nt 
f or m ulati o n e xci pie nts t o ai d t he de vel o p me nt of a n a ge a p pr o priate pe diatric sis u nat o vir 
f or m ulati o n.
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 assess t he palata bilit y attri b utes of sis u nat o vir i n 
differe nt f or m ulati o ns

Palata bilit y Assess me nt Q uesti o n naire Sc ori n g Metrics: 
m o ut h feel, bitter ness, s weet ness, s o ur ness, salti ness, 
t o n g ue/ m o ut h b ur n, o verall li ki n g.
Sec o n d ar y: 
Sec o n d ar y: 

T o assess safet y a n d t olera bilit y f oll o wi n g oral 
a d mi nistrati o n of eac h sis u nat o vir f or m ulati o ns

Assess me nt of treat me nt e mer ge nt a d verse e ve nts 
(T E A Es ), cli nical la b orat or y a b n or malities a n d vital 
si g ns.
O ver all Desi g n :
T his is a si n gle -bli n d, ra n d o mize d, m ulti -peri o d st u d y i n healt h y male a n d/ or fe male a d ult 
partici pa nts. A p pr o xi matel y  1 2 partici pa nts will assess t he palata bilit y attri b utes of a t otal of 
6 f or m ulati o ns ( F or m ulati o ns A t o F) o ver 2 da y s i n a cr oss o ver ma nner. T here will be a 
ma xi m u m of 4 peri o ds eac h da y , a n d 1 f or m ulati o n will be a d mi nistere d at eac h peri o d f or 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9
tasti n g i n a bli n de d fas hi o n, e xce pt o n Da y 2 w here t here will be 1 peri o d wit h n o 
a d mi nistrati o n . A mi ni m u m of 3 partici pa nts fr o m eac h ge n der is re q uire d. 
All partici pa nts will be disc har ge d o n Da y  2 after c o m pleti o n of all re q uire d assess me nts. If 
t he partici pa nt acci de ntall y i n gests t he taste sa m ple c o ntai ni n g t he acti ve i n gre die nt, he/s he 
will n ot be per mitte d t o c o nti n ue e val uati n g a n y f urt he r taste sa m ples a n d will be wit h dra w n 
fr o m t he st u d y. 
N u m ber of P artici p a nts:
A p pr o xi matel y  1 2 partici pa nts will be e nr olle d i n t he st u d y.
N ote: “E nr olle d ” mea ns a partici pa nt ’s a gree me nt t o partici pate i n a cli nical st u d y f oll o wi n g 
c o m pleti o n of t he i nf or me d c o nse nt pr ocess a n d ra n d o mizati o n. 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 vity. 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 
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:
1.
Male a n d fe male partici pa nts a ge d 1 8 ye ars or ol der ( or t he mi ni m u m a ge of c o nse nt 
i n acc or da nce wit h l ocal re g ulati o ns) at scree ni n g w h o are o vertly healt h y as 
deter mi ne d b y me dical e val uati o n i ncl u di n g me dical hist or y , p h ysical e xa mi nati o n, 
la b orat or y tests, bl o o d press ure, p ulse rate a n d sta n dar d 1 2-lea d electr ocar di o gra m
(E C G ).
2.
B o d y mass i n de x ( B MI ) of 1 6 -3 2 k g/ m 2; a n d a t otal b o d y wei g ht > 4 5 k g ( 1 1 0 l b).
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:
1.
E vi de nce or hist or y  of cli nicall y si g nifica nt he mat ol o gical, re nal, e n d ocri ne, 
p ul m o nar y , gastr oi ntesti nal, car di o vasc ular, he patic, ps yc hiatric, ne ur ol o gical, or 
aller gic disease (i ncl u di n g dr u g 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).
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 0

Hist or y  of h u ma n i m m u n o deficie nc y  vir us (HI V) i nfecti o n, he patitis B, or 
he patitis C; p ositi ve testi n g f or HI V, he patitis B s urface a nti ge n (H Bs A g ), or 
he patitis C a nti b o d y (H C V A b ). He patitis B vacci nati o n is all o we d.
2.
A n y  me dical or psyc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/ be ha vi or or la b orat or y a b n or malit y or ot her c o n diti o ns t hat ma y 
i ncrease t he ris k of st u dy partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, ma ke t he 
partici pa nt i na p pr o priate f or t he st u d y.
3.
C o n diti o ns t hat affect a bilit y  t o taste e g, d y s ge usia, res pirat or y i nfecti o n, c ol d, etc.
4.
Hist or y  of hy p erse nsiti vit y t o t he acti ve c o m p o un ds or t o a n y  i nacti ve i n gre die nts 
(e xci pie nts) c o ntai ne d i n t he f or m ulati o ns.
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 m o derate/str o n g c yt oc hr o me P 4 5 0 3 A ( C Y P 3 A) 
i n d ucers or i n hi bit ors w hic h are pr o hi bite d wit hi n 1 4 da ys pl us 5 half-li ves pri or t o 
t he first d ose of st u dy i nter ve nti o n . 
6.
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). Partici pati o n i n 
st u dies of ot her i n vesti gati o nal pr o d ucts ( dr u g or vacci ne) at a ny ti me d uri n g t heir 
partici pati o n i n t his st u d y . 
7.
A p ositi ve uri ne dr u g test at scree ni n g or a d missi o n. A si n gle re peat f or p ositi ve dr u g 
scree n ma y be all o we d.
8.
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/ser u m pre g na nc y 
test i n w o ma n/ w o me n of c hil d beari n g p ote ntial ( W O C B P) at Da y - 1
9.
Use of t o bacc o/ nic oti ne c o ntai ni n g pr o d ucts, as i n dicate d b y a p ositi ve uri ne c oti ni ne 
test at scree ni n g or a d missi o n.
1 0. Scree ni n g s u pi ne bl o o d press ure (B P ) ≥1 4 0 m m H g (s ys t olic) or ≥9 0 m m H g 
( diast olic) for partici pa nts < 6 0 y ears; a n d ≥1 5 0/ 9 0 m m H g f or partici pa nts ≥6 0 y ears 
ol d, f oll o wi n g at least 5 mi n utes of s u pi ne rest. If s y st olic B P is ≥ 1 4 0 or 1 5 0 m m H g 
( base d o n a ge) or diast olic ≥9 0 m m H g, t he B P s h o ul d be re peate d 2 m ore ti mes a n d 
t he a vera ge of t he 3 B P val ues s h o ul d be use d t o deter mi ne t he partici pa nt’s 
eli gi bilit y. 
1 1. Re nal i m pair me nt as defi ne d b y  a n esti mate d gl o mer ular filtrati o n rate (e G F R ) ( u nits 
of m L / mi n/ 1. 7 3 m²) < 6 0 m L / mi n(/ 1. 7 3 m²). Si nce partici pa nts are 1 8 years a n d a b o ve, 
2 0 2 1 c hr o nic ki d ne y  disease e pi de mi ol o g y (C K D -E PI ) e G F R (c o m bi ne d ser u m 
creati ni ne [Screat ] a n d ser u m c ystati n C [Sc y s]) is t he rec o m me n de d f or m ula t o 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 1
deter mi ne eli gi bilit y  a n d t o pr o vi de a baseli ne t o q ua ntif y a n y s u bse q ue nt ki d ne y 
safety e ve nts.
1 2. Sta n dar d 1 2 -lea d E C G t hat de m o nstrates cli nically rele va nt a b n or malities t hat ma y 
affect partici pa nt safet y or i nter pretati o n of st u d y res ults (e g, Q Tc c orrecte d usi n g 
Fri dericia’s f or m ula [ Q Tc F ] > 4 5 0 ms, c o m plete left b u n dle bra nc h bl oc k [L B B B ], 
si g ns of a n ac ute or i n deter mi nate- a ge m y ocar dial i nfarcti o n, S T -T i nter val c ha n ges 
s u g gesti ve of m yocar dial isc he mia, sec o n d- or t hir d - de gree A V bl oc k, or seri o us 
bra d yarr h yt h mias or tac h y arr h yt h mias). If Q Tc F e xcee ds 4 5 0 ms, or Q R S e xcee ds 
1 2 0 ms, t he E C G s h o ul d be re peate d t wice a n d t he a vera ge of t he 3 Q Tc F or Q R S 
val ues use d t o deter mi ne t he partici pa nt’s eli gi bilit y. C o m p uter -i nter prete d E C Gs 
s h o ul d be o verrea d by a p h ysicia 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 3. 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: 

Ala ni ne a mi n otra nsferase ( A L T ), as partate a mi n otra nsferase (A S T ), bilir u bi n 
(Bili ) ≥ 1. 0 5 × u p per li mit of n or mal (U L N ). Partici pa nts wit h a n ele vate d t otal 
bilir u bi n c o nsiste nt wit h Gil bert’s Disease s h o ul d ha ve a direct bilir u bi n meas ure d 
a n d w o ul d be eli gi ble f or t his st u d y pr o vi de d t he direct bilir u bi n le vel is ≤ U L N.
St u d y Ar ms a n d D ur at i o n:
T he t otal pla n ne d 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 c o ntact, 
is a p pr o xi matel y 5 t o 8 wee ks. T he st u d y c o nsists of a n i nitial scree ni n g peri o d of u p t o 
2 8 da y s pri or t o t he first a d mi nistrati o n of st u d y i nter ve nti o n, a d missi o n t o t he cli nical 
researc h u nit (C R U ) o n Da y  - 1 a n d pla n ne d disc har ge o n D a y  2, f oll o wi n g c o m pleti o n of 
assess me nts, as well as a f oll o w-u p c o ntact t hat will occ ur 2 8 -3 5 da y s after t he fi nal 
palata bilit y  assess me nt of P F- 0 7 9 2 3 5 6 8.
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) Palata bilit y i n 
Li q ui d Ve hicles
Bitre x
T y pe
Dr u g
E xci pie nt 
Use
E x peri me ntal
F or assess me nt of bitter ness e n d p oi nt
I M P or NI M P/ A x M P
I n vesti gati o nal me dici nal pr o d uct (I M P)  
Au xiliar y me dici nal pr o d uct ( A x M P )
D ose F or m ul ati o n
1 0 0 m g sis u nat o vir (t w o 5 0 m g ca ps ules) dr y 
p o w der ble n d i ncl u de d wit h var yi n g 
e xci pie nts, dis perse d i n 0. 9 % s o di u m c hl ori de 
f or oral r o ute of a d mi nistrati o n (R O A )
7. 5 μ g d ose i n 1 5 m L water
U nit D ose Stre n gt h(s)
5 0 m g ca ps ule
2 μ g
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 2
St u d y I nter ve nti o n(s)
D os a ge Le vel(s)
R o ute of A d mi nistr ati o n
Oral/ “S wirl a n d S pit”
Oral/ “S wirl a n d S pit”
S o urci n g
Sis u nat o vir: Pr o vi de d ce ntrall y b y t he s p o ns or
 
Stra w berr y fla v o ur & E xci pie nts: 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
P ac k a gi n g a n d L a beli n g
St u d y i nter ve nti o n will be pr o vi de d i n b ul k. 
Eac h c o ntai ner will be la bele d as re q uire d per 
c o u ntr y re q uire me nt. C R U Staff will pre pare 
i n di vi d ual d oses (ca ps ule c o nte nt + li q ui d) f or 
a d mi nistrati o n per e xte m p ora ne o us 
dis pe nsi n g rec or d ( E D R ).
St u d y i nter ve nti o n will be pr o vi de d i n 
b u l k. Eac h c o ntai ner will be la bele d as 
re q uire d per c o u ntr y re q uire me nt.
Si n gle Refere nce S afet y 
D oc u me nt ( S R S D )
I n vesti gat or’s Br oc h ure (I B)
U nite d States P har mac o p oeia ( U S P)
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
Bitre x, De nat o ni u m Be nz oate
St u d y Ar m(s)
A r m  Title
Peri o d 1 t o Peri o d 8
A r m  Descri pti o n
Partici pa nts will recei ve st u d y i nter ve nti o n i n a ra n d o mize d cr oss o ver ma n ner at eac h 
peri o d, u p t o 4 ti mes a da y f or Da y 1 a n d Da y 2.
St atistic al Met h o ds :
T he pr o p ose d sa m ple size f or t he st u d y of a p pr o xi matel y  1 2 partici pa nts is e m piricall y 
selecte d. F or palata bilit y assess me nt, t he data use d i n t he a nalys is will be tra nscri be d a n d 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)
C CI
C CI


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 3
rescale d t o a sc ore fr o m 0 t o 1 0 0 fr o m t he ra w meas ure me nts o n t he q uesti o n naire. T he 
palata bilit y attri b utes ( m o ut h feel, bitter ness, s weet ness, s o ur ness, salti ness, t o n g ue/ m o ut h 
b ur n, o verall li ki n g) fr o m t he palata bilit y q uesti o n naires will be liste d a n d descri pti vely 
s u m marize d. F or t h e sec o n dar y o bjecti ve of safet y, data will be s u m marize d descri pti vely 
t hr o u g h data ta b ulati o n, descri pti ve statistics, cate g orical s u m maries, a n d gra p hical 
prese ntati o ns, as a p pr o priate, i n acc or da nce wit h Pfizer Data Sta n dar ds.
Et hic al C o nsi der ati o ns:
Sis u nat o vir is a p ote ntial ne w, p har mac ol o gical a ge nt f or t he treat me nt of res pirat or y 
s yn c y tial vir us (R S V ) a n d is n ot e x pecte d t o pr o vi de a n y cli nical be nefit t o healt h y 
partici pa nts. T his st u d y is desi g ne d f or palata bilit y  assess me nts t o i nf or m de vel o p me nt of 
pe diatric f or m ulati o n f or sis u nat o vir. C o nsi deri n g 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 f or t he a d va nce me nt of p ote ntial treat me nt f or R S V i nfecti o n.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 4
1. 2. Sc he m a
T a ble 1 .
S a m ple D osi n g Sc he me
Sessi o n 1 ( D a y 1)
Sessi o n 2 ( D a y 2)
Peri o d 1 
Peri o d 2 
Peri o d 3 
Peri o d 4 
Peri o d 5 
Peri o d 6 
Peri o d 7 
Peri o d 8
N = 3
A
B
D
C
A
E
N o
F
N = 3
B
C
A
D
E
F
A
N o
N = 3
C
D
B
A
F
N o
E
A
N = 3
D
A
C
B
N o
A
F
E
Treat me nt A:  
m g/ m L Sis u nat o vir
Treat me nt B:  
m g/ m L Sis u nat o vir, 
 
Treat me nt C:
Treat me nt D:  
m g/ m L Sis u nat o vir a n d
Treat me nt E:  
m g/ m L Sis u nat o vir a n d
Treat me nt F:  
m g/ m L Sis u nat o vir, 
 
 
N o : N o a d mi nistrati o n a n d i n dicate d as ‘ X’ i n ra n d o mizati o n
N ote: 
 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( 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
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 5
1. 3. S c he d ule of Acti v ities
T he S o A ta ble pr o vi des a n o ver vie w of t he pr ot oc ol visits a n d pr oce d ures. Refer t o t he S T U D Y A S S E S S M E N T S A N D 
P R O C E D U R E S secti o n of t he pr ot oc ol f or detaile d i nf or mati o n o n eac h pr oce d ure a n d assess me nt re q uire d f or c o m plia nce wit h t he 
pr ot oc ol. 
T he i n vesti gat or ma y  sc he d ule visits ( u n pla n ne d visits) i n a d ditio 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 2 .
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 4
Peri o d 5 t o 8
F/ U
E arl y 
Disc o nt
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
2 8 -3 5 
D a ys

All scree ni n g s h o ul d be d o ne ≤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).

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d m ust occ ur 2 8 
t o 3 5 da ys after a d mi nistrati o n of t he fi nal d ose of st u d y 
i nter ve nti o n.
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
X
I ncl usi o n/e xcl usi o n criteria
X
X
Me dical/ me dicati o n hist or y
X
X
P h ysical e xa m
X  
X

P E  at Scree ni n g or 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.
Safet y la b orat or y
X  
X
X
X

Safet y la b orat or y i ncl u des he mat ol o g y, c he mistr y, a n d 
uri nal ysis, w hic h are liste d i n A p pe n di x 2 .

O n Da y 2 , safet y la bs will be ta ke n after c o m pleti n g t he fi nal 
palata bilit y assess me nt a n d pri or t o disc har ge.

A d diti o nal assess me nt ma y be perf or me d at t he discreti o n of t he 
i n vesti gat or.
De m o gra p h y
X
Pre g na nc y test ( W O C B P o nl y)
X
X
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 a n d c oti ni ne testi n g
X
X
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 6
T a ble 2 .
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 4
Peri o d 5 t o 8
F/ U
E arl y 
Disc o nt
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
2 8 -3 5 
D a ys

All scree ni n g s h o ul d be d o ne ≤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).

F oll o w -u p ma y occ ur via tele p h o ne c o ntact a n d m ust occ ur 2 8 
t o 3 5 da ys after a d mi nistrati o n of t he fi nal d ose of st u d y 
i nter ve nti o n.
1 2 -Lea d E C G (si n gle)
X
X
X
X

O n Da y 1 , si n gle E C G will be ta ke n pri or t o start of palata bilit y 
assess me nt .

O n Da y 2 , si n gle E C G will be ta ke n after c o m pleti n g t he fi nal 
palata bilit y assess me nt a n d pri or t o disc har ge.
Bl o o d press ure a n d p ulse rate 
X
X
X
X

O n Da y 1 , bl o o d press ure a n d p ulse rate will be ta ke n pri or t o 
start of palata bilit y assess me nt .

O n Da y 2 , bl o o d press ure a n d p ulse rate will be ta ke n after 
c o m pleti n g t he fi nal palata bilit y assess me nt a n d pri or t o 
disc har ge.
HI V, H Bs A g, H C V A b 
X
St u d y i nter ve nti o n 
a d mi nistrati o n
X
X

See Secti o n 6. 1. 1 .
Palata bilit y Assess me nts
X
X

Palata bilit y assess me nts will be c o m plete d at 1 mi n 
(i m me diatel y f oll o wi n g d ose), 5 mi n, 1 0 mi n, a n d 2 0 mi n after 
tasti n g eac h f or m ulati o n .

At least 6 0 -mi n ute was h o ut is re q uire d a n d n o m ore t ha n 4 
f or m ulati o ns will be taste d eac h da y (see Secti o n 5. 3. 2 a n d 
Secti o n 6. 1. 1 f or details)
C R U disc har ge 
X
X

Partici pa nts will be disc har ge d after c o m pleti n g t he fi nal 
palata bilit y a n d safet y assess me nt o n Da y 2 .
Pri or/c o nc o mita nt me dicati o n  
X  
X


X  
X
Seri o us a n d n o nseri o us A E 
m o nit ori n g
X
 


X  
X

See Secti o n 8. 4. 3 f or f oll o w-u p A E a n d S A E assess me nts.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 7
2. I N T R O D U C TI O N
Sis u nat o vir ( P F-0 7 9 2 3 5 6 8, f or merl y R V 5 2 1) is a n orall y a d mi nistere d R S V F-pr otei n 
i n hi bit or t hat is c urre ntl y 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. Sis u nat o vir is a n i n hi bit or of R S V f usi o n ( F) pr otei n 
me diate d f usi o n t hat is c urre ntl y bei n g i n vesti gate d f or t he treat me nt of R S V i nfecti o n .
2. 1. St u d y R ati o n ale 
T he p ur p ose of t h is st u d y is t o perf or m p alata bilit y assess me nts t o ai d i n t he de vel o p me nt of 
pe diatric f or m ulati o ns of sis u nat o vir.
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 mil d 
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, I C U a d missi o n a n d e ve n deat h. 2 ,3 ,4
T he c urre nt ma na ge me nt of R S V i nfecti o n i ncl u des 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 ylactic m o n ocl o nal a nti b o d y t hat has 
bee n s h o w n t o pr 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 o r 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 nc yt ia 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.
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 on i n a h u ma n air wa y  e pit helial cell m o del. 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 8

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.
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 pe cti 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 6 7 %, 3 8 %, 5 2 %, 2 7 %, a n d 4 8 % 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 dies 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 4 2 1 0 0 4), i n vitr o st u dies 
i n dicate that 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 2 C 9 a n d 2 D 6. 

Base d o n E M A g ui da nce, i n vitr o st u dies i n dicate a D DI ris k e xists f or 
O A T P 1 B 1/ 1 B 3, O C T 1, M A T E 1, O C T 2, a n d O A T 3. H o we ver, rati os of u n b o u n d 
he pa tic 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 O A T Ps, O C T 2, a n d O A T 3. T he p har mac o ki netics of O C T 1 a n d M A T E 1 
s u bstrates ma y be altere d w he n c o-a d mi nistere d wit h sis u nat o vir.

Base d o n calc ulati o ns fr o m E M A g u i da nce 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 1 A 2, 2 B 6, 2 C 9, 2 C 1 9, a n d 3 A 4. T he D DI wit h C Y Ps 1 A 2, 2 C 9, 
a n d 2 C 1 9 is pre dicte d t o be mi ni mal ( pre dicte d less t ha n 2 5 % i ncrease i n A U C of a 
se nsiti ve s u bstrate) a n d D DI wit h C Y P 2 B 6 is pre dicte d t o be wea k. 

I n vitr o st u dies 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). 

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 
i n vitr o 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 le vels. 
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 uc e d f o o d c o ns u m pti o n
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 1 9
acc o m pa nie d b y a d verse cli nical o bser vati o n of var yi n g se verit y. I n d o gs, t here was 
d ose -relate d i nci de nce of e mesis a n d li q ui d feces at ≥1 5 m g/ k g/ da y . T he ke y tar get 
or ga n f or t o xicit y  i n a d ult a ni mals was t he he pat o biliar y sys te m, w hic h i ncl u de d b ot h 
de g e 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 Cma 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 on. I n ra b bit, 
mater nal t o xicit y  was li mite d t o l o wer b o d y wei g ht gai n a n d f o o d i nta ke at 
4 5 m g/ k g/ da y . T he N O A E L f or e m br yo- fetal de vel o p me nt i n ra b bit was 
4 5 m g/ k g/ da y , c orres p o n di n g t o a sys te mic mater nal e x p os ure ( A U C2 4) of 
2 2 0 n g• h/ m L o n Da y  1 6 of gestati o n.
Refer t o t he sis u nat o vir I B f or f urt her details.
2. 2. 4. Cli nic al O ver vie w
T a ble 3 .
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 ul ati o n Use d
C 5 2 4 1 0 0 1
( pre vi o usl y 
R E V C 0 0 1 a) 
(c o m plete d)
P hase 1, 
ra n d o mize d, d o u ble 
bli n d, place b o 
c o ntr olle d, safet y, 
t olera bilit y, P K, 
f o o d-effect of S A D 
a n d M A D
Heal t h y partici pa nts
D ose ra n ge: 1 0 m g –
5 2 5 m g ( S A D); 
3 6 partici pa nts
D ose ra n ge: 1 7 5 m g 
– 3 5 0 m g; BI D 
( 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 
BI D 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 
P hase 1, a da pti ve, 
part ra n d o mise d, 
part o pe n -la bel, dr u g 
Healt h y partici pa nts 
2 0 0 m g; BI D; 
6 2 Partici pa nts 
DI C
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 0
T a ble 3 .
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 ul ati o n Use d
R E V C 0 0 4) 
(c o m plete d)
i nteracti o ns, safet y, 
t olera bilit y 
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 water (fe d)
1 ×: D P B dis perse d 
i n water (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 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 nts 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 5 Dece m ber 2 0 2 2, 5 1 pe diatric patie nts 
h os pitalize d d ue t o R S V - L R TI ha ve recei ve d eit her a si n gle d ose ( N = 1 9) or u p t o 5 da ys 
m ulti ple d ose ( BI D) ( N = 3 2) of sis u nat o vir i n t he o n g oi n g C 5 2 4 1 0 0 3 st u d y.
I n a d ult st u dies, the 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. 
As of 1 8 A pril 2 0 2 3 , i n c hil dre n w h o recei ve d a si n gle d ose ( Part A) or m ulti ple d oses ( Part 
B) of sis u nat o vir, all A Es were of mil d or m o derate i nte nsit y  ( St u d y C 5 2 4 1 0 0 3). A d verse 
e ve nts were re p orte d i n 1 1 of 1 9 partici pa n ts d ose d i n Part A, a n d i n 1 2 of 3 1 partici pa nts 
d ose d i n Part B . Dis persi o n i n breast mil k, f or 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 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 
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. T here has bee n 1 seri o us A E of fe ver re p orte d i n t he pe diatric st u d y 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 1
( C 5 2 4 1 0 0 3) i n a c hil d h os pitalize d wit h R S V i nfecti o n w h o recei ve d a si n gle d ose of 
sis u nat o vir. T his was c o nsi dere d seri o us beca use it pr ol o n ge d h os pitalizati o n, b ut t he S A E 
was re p orte d as n ot relate d t o I M P. I n St u d y  C 5 2 4 1 0 0 2 t here was 1 S A E of s u b-ac ute 
m y ocar ditis re p orte d f or a s u bject o n place b o; t his was c o nsi dere d t o be ca us all y relate d t o 
t he c halle n ge vir us.
I n a d ults, sis u nat o vir is sl o wl y a bs or be d reac hi n g ma xi m u m plas ma c o nce ntrati o ns (T ma x ) at 
5 - 6 h o urs wit h a relati vel y m o derate 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 d y 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 di es. 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.
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. T his st u d y als o 
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.
I n a n R S V c halle n ge st u d y (C 5 2 4 1 0 0 2 ), 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 unat 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 ys). Res ults f or t he A U C of t otal s ym pt o m sc ore were c o nsiste nt 
wit h t he viral l oa d A U C. Ge o metric mea n A U Cs of t otal s y m pt o m sc ore were 1 9 5. 5 6, 3 0. 7 9 
a n d 3 1. 7 6 h o urs x sc ore f or place b o, 2 0 0 m g sisu nat o vir a n d 3 5 0 m g sis u nat o vir, 
res pecti vely. T he re d ucti o n i n A U Cs of t otal s y m pt o m sc ore c o m pare d wit h place b o was 
statisticall y si g nifica nt f or b ot h sis u nat o vir treat me nt gr o u ps; p = 0. 0 0 9 ( 7 0. 8 4 %) a n d p = 0. 0 0 2 
( 7 4. 4 2 %), ( 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, 
res pecti vely.
M ore detaile d i nf or mati o n a b o ut res ults of cli nical st u dies f or sis u nat o vir ma y  be f o u n d i n t he 
I B, w hic h is t he S R S D f or t his st u d y.
2. 3. Be nefit/ Ris k Assess me nt
Sis u nat o vir is 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 a n d is n ot 
e x pecte d t o pr o vi de a n y cli nical be nefit t o healt h y partici pa nts. T his st u d y  is desi g ne d f or
palata bilit y  assess me nts t o i nf or m de vel o p me nt of pe diatric f or m ulati o n f or sis u nat o vir. 
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 n patie nt m o nit ori n g of t he partici pa nts 
f oll o wi n g a d mi nistrati o n of t he st u d y i nter ve nti o ns, li mitati o n o n t he n u m ber of st u d y 
i nter ve nti o ns a d mi nistere d eac h da y, a n d t he r e q uire me nt t o s pit o ut t he st u d y i nter ve nti o n 
after tasti n g.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 2
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 E s 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.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 3
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 is 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.
Partici pa nts will be as ke d t o s pit o ut t he st u d y 
i nter ve nti o n after tasti n g. I n t he case of acci de ntal 
i n gesti o n, partici pa nts will n ot be per mitte d t o 
c o nti n ue wit h f urt her palata bilit y assess me nts i n 
t he st u d y.
Sta n dar d m o nit ori n g i ncl u di n g la b orat or y (ie, 
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 feces i n d o gs at d oses ≥1 5 m g/ k g/ da y i n 
st u dies u p t o 2 8 da ys. A d diti o nall y, i nfla m mati o n 
i n d u o de n u m, gall bla d der, a n d li ver at 4 5 
m g/ k g/ da y n ote d i n 2 8 -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 wit h mil d GI A Es.
Partici pa nts will be as ke d t o s pit o ut t he st u d y 
i nter ve nti o n after tasti n g. I n t he case of acci de ntal 
i n gesti o n, partici pa nts will n ot be per mitte d t o 
c o nti n ue wit h f urt her palata bilit y assess me nts i n 
t he st u d y.
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 Es. If nee de d, 
palliati ve alle viati n g meas ures s uc h care as 
a ntie metics ma y be pr o vi de d. 
Car di o vasc ular effects
M y ocar dial de ge nerati o n a n d necr osis were 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 -da 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.
Partici pa nts will be as ke d t o s pit o ut t he st u d y 
i nter ve nti o n after tasti n g. I n t he case of acci de ntal 
i n gesti o n, partici pa nts will n ot be per mitte d t o 
c o nti n ue wit h f urt her palata bilit y assess me nts i n 
t he st u d y.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 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
Sis u nat o vir is n ot e x pecte d t o pr o vi de a n y cli nical be nefit t o healt h y partici pa nts i n t his 
st u d y.
Ta ki n g i nt o acc o u nt t he meas ures t o mi ni mize ris k t o st u d y  partici pa nts, t he p ote ntial ris ks 
i de ntifie d i n ass ociati o n wit h sis u nat o vir are j ustifie d b y t he a ntici pate d be nefits f or t he 
a d va nce me nt of p ote ntial treat me nt f or R S V i nfecti o n.
3. O B J E C TI V E S A N D E N D P OI N T S
O bjecti ves
E n d p oi nts
Pri m ar y : 
Pri m ar y : 

T o assess t he palata bilit y attri b utes of s is u nat o vir i n 
differe nt f or m ulati o ns

Palata bilit y Assess me nt Q uesti o n naire Sc ori n g Metrics: 
m o ut h feel, bitter ness, s weet ness, s o ur ness, salti ness, 
t o n g ue/ m o ut h b ur n, o verall li ki n g.
Sec o n d ar y:
Sec o n d ar y : 

T o assess safet y a n d t olera bilit y f oll o wi n g oral 
a d mi nistrati o n of eac h sis u nat o vir f or m ulati o ns

Assess me nt of T E A Es, cli nical la b orat or y a b n or malities 
a n d vital si g ns.
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a si n gle -bli n d, ra n d o mize d, m ulti -peri o d st u d y i n healt h y male a n d/ or fe male a d ult 
partici pa nts. A p pr o xi matel y 1 2 partici pa nts will assess t he palata bilit y attri b utes of a t otal of 
6 f or m ulati o ns ( F or m ulati o ns A t o F ) o ver 2 d a y s i n a cr oss over ma n ner . T here will be a 
ma xi m u m of 4 peri o ds eac h da y , a n d o ne f or m ulati o n will be a d mi nistere d at eac h peri o d f or 
tasti n g i n a bli n de d fas hi o n, e xce pt o n Da y 2 w here t here will be o ne peri o d wit h n o 
a d mi nistrati o n. A mi ni m u m of 3 partici pa nts fr o m eac h ge n der is re q uire d.
All partici pa nts will be disc har ge d o n Da y  2 after c o m pleti o n of all re q uire d assess me nts. If 
t he partici pa nt acci de ntall y i n gests t he taste sa m ple c o ntai ni n g t he acti ve i n gre die nt, he/s he 
will n ot be per mitte d t o c o nti n ue e val uati n g a n y f urt her taste sa m ples a n d will be wit h dra w n 
fr o m t he st u d y. 
T he t otal pla n ne d 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 c o ntact, 
is a p pr o xi matel y 5 t o 8 wee ks. T he st u d y c o nsists of a n i nitial scree ni n g peri o d of u p t o 
2 8 da y s pri or t o t he first a d mi nistrati o n of st u d y i nter ve nti o n , a d missi o n t o t he C R U o n 
D a y  -1 a n d pla n ne d disc har ge o n D a y  2, f oll o wi n g c o m pleti o n of assess me nts per S o A , a n d a
f oll o w-u p c o ntact t hat will occ ur 2 8 -3 5 da y s after t he fi nal palata bilit y assess me nt of 
P F - 0 7 9 2 3 5 6 8.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 5
I n t he e ve nt w here t he partici pa nt acci de ntall y i n gests t he taste sa m ple c o ntai ni n g t he acti ve 
i n gre die nt, he/s he will n ot be per mitte d t o c o nti n ue e val uati n g a ny f urt her taste sa m ples a n d 
will be wit h dra w n fr o m t he st u d y . 
Partici pa nts w h o disc o nti n ue fr o m t he st u d y ma y be re pla ce d at t he s p o ns or’s discreti o n. T he 
re place me nt partici pa nt will recei ve t he sa me treat me nt se q ue nces as t he partici pa nt w h o 
disc o nti n ue d.
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
T o mi ni mize p ote ntial bias i n t he assess me nt of palata bilit y  b y partici pa nts, t his st u d y will be 
si n gle-bli n de d. A cr oss o ver desi g n is pla n ne d he nce all o wi n g f or wit hi n-partici pa nt 
c o m paris o n of t he palata bilit y sc ores, a n d t he a d mi nistrati o n of a c o ntr ol f or m ulati o n 
(
m g/ m L sis u nat o vir
 will be a d mi nistere d o n eac h da y of t he 
assess me nt t o c o ntr ol f or p ote ntial differe nces bet wee n da y s. Bitre x ser ves as p ositi ve c o ntr ol 
t o c o nfir m if partici pa nts ca n taste bitter ness. A d diti o nall y , it ma y  pr o vi de bri d gi n g 
be nc h mar k t o c o m pare a ga i nst ot her mar kete d pr o d ucts as well as t o assist t he f or m ulati o n of 
place b o f or pe diatric st u dies t o ha ve c o m para ble bitter ness le vels if prese nt.
T he palata bilit y  of sis u nat o vir will be assesse d t o ai d i n de vel o p me nt of pe diatric 
f or m ulati o ns. Palata bilit y will be assesse d by all partici pa nts i n a t otal of 8 peri o ds wit h a 
mi ni m u m of 1 h o ur bet wee n eac h peri o d , w hic h is base d o n t he t y pical was h o ut of a n h o ur 
use d f or palata bilit y  assess me nts. The f or m ulati o n will be s wirle d i n t he m o ut h a n d s pat o ut 
si nce it is n ot necessar y t o c o ns u me t he st u d y i nter ve nti o n t o assess palata bilit y. A PI 
c o m bi ne d wit h fla v or, s weete ner or a c o m bi nati o n of b ot h will be assesse d t o u n dersta n d 
w hic h e xci pie nts i m pr o ve palata bilit y  a n d j ustif y t heir i ncl usi o n i n t he pe diatric for m ulati o n. 
D ue t o t he p ote ntial effect of s m o ki n g o n taste se nsiti vit y , partici pa nts w h o s m o ke or use 
t o bacc o/ nic oti ne c o ntai ni n g pr o d ucts are e xcl u de d fr o m t his st u d y. Partici pa nts wit h 
c o n diti o ns t hat affect a bilit y  t o taste (e g, d y s ge usia, res pirat or y i nfecti o n, c ol d, etc) will als o 
be e xcl u de d.
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 s 2. 2. 2 a n d 2. 2. 4 , 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 C Y P 2 B 6. 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 TI C Y P 2 B 6 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, s tr 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 M A T E 1 a n d O C T 1 
i n hi biti 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 8 .
4. 2. 1. C h oice of C o ntr ace pti o n/ B arrier Re q uire me nts 
H u ma n re pr o d ucti ve safet y  data are li mite d f or t he st u d y i nter ve nti o n, b ut t here is n o 
s us pici o n of h u ma n terat o ge nicit y base d o n t he i nte n de d p har mac ol o g y of t he 
c o m p o u n d. T heref ore, t he 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 (see 
A p pe n di x 4 ).
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)
C CI
C CI


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 6
4. 3. J ustific ati o n f or D ose
T he d os i n g c o nce ntrati o n i n t his palata bilit y st u d y 
 
) was selecte d t o be cl ose t o t he 
a ntici pate d sis u nat o vir c o nce ntrati o n f or oral d osi n g i n pla n ne d pe diatric st u dies. 
A p pr o xi matel y
m L  of t he  
 m g/ m L sis u nat o vir s us pe nsi o n will be a d mi nistere d. 
A ma xi m u m of 4 differe nt f or m ulati o ns, w hic h is a t otal of 2 0 0 m g of sis u nat o vir or less, will 
be a d mi nistere d t o t he partici pa nts eac h da y , o ver 2 da y s. Partici pa nts will be re q uire d t o 
s wirl t he st u d y i nter ve nti o n i n t heir m o ut h f or 1 0 sec o n ds a n d s pit it o ut i nstea d of 
s wall o wi n g. Alt h o u g h t he b uccal a bs or pti o n of P F - 0 7 9 2 3 5 6 8 is u n k n o w n, t he Tma x of 
sis u nat o vir i n P hase 1 st u dies was ar o u n d 5 - 6 h o urs , i ndicati n g a l o n g a bs or pti o n p hase
( Secti o n 2. 2. 4 ). T he brief c o ntact of t he test f or m ulati o ns wit h t he oral ca vit y d uri n g t he 
palata bilit y  testi n g is n ot e x pecte d t o res ult i n a p precia ble a bs or pti o n. Wit h
a c o nser vati ve 
ass u m pti o n t hat t he palata bilit y  assess me nt s i n t his st u d y res ults i n t he e q ui vale nce of 
s wall o wi n g t he a d mi nistere d f or m ulati o ns, t he ma xi m u m of 2 0 0 m g per da y  will still be less 
t ha n d oses of u p t o 3 5 0 m g BI D (t otal dail y d ose of 7 0 0 m g) f o u n d t o be safe a n d ge nerall y
well t olerate d i n t he viral c halle n ge st u d y ( C 5 2 4 1 0 0 2) as well as ot her sis u nat o vir P hase 1 
st u dies c o n d ucte d t o date.
4. 4. E n d of St u d y Defi niti o n
T he e n d of t he st u d y is defi ne d as t he date of t he last visit of t he last partici pa nt i n t he st u d y 
or last sc he d ule d pr oce d ure s h o w n i n t he S o A f or t he last partici pa nt i n t he trial gl o bally.
A partici pa nt is c o nsi dere d t o ha ve c o m pl ete 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 or t he last sc he d ule d pr oce d ure s h o w n i n t he S o A .
5. S T U D Y P O P U L A TI O N
T his st u d y  ca n f ulfill its o bjecti ves o nl y if a p pr o priate partici pa nt s are e nr olle d, i ncl u di n g 
partici pa nts acr oss di verse a n d re prese ntati ve racial a n d et h nic bac k gr o u n ds. If a 
prescree ni n g t o ol is utilize d f or st u d y recr uit me nt p ur p oses, it will i ncl u de c ollecti o n of 
i nf or mati o n t hat reflects t he e nr oll me nt of a di verse partici pant p o p ulati o n i ncl u di n g, w here 
per mitte d u n der l ocal re g ulati o ns, a ge, se x, race, a n d et h nicit y . T he f oll o wi n g eli gi bilit y  
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:
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)
C CI
C CI
C CI


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 7
A ge a n d Se x :
1.
Male a n d fe male partici pa nts a ge d 1 8 ye ars or ol der ( or t he mi ni m u m a ge of c o nse nt 
i n acc or da nce wit h l ocal re g ulati o ns) at scree ni n g w h o are o vertly healt h y as 
deter mi ne d b y me dical e val uati o n i ncl u di n g me dical hist or y, p h ys ical e xa mi nati o n, 
la b orat or y tests, bl o o d press ure, p ulse rate a n d sta n dar d 1 2- lea d E C G.
Refer t o A p pe n di x 4 f or re pr o d ucti ve criteria f or male (Secti o n 1 0. 4. 1 ) a n d fe male 
(Secti o n 1 0. 4. 2 ) partici pa nts.
Ot her I ncl usi o n Criteri a :
2.
B MI of 1 6 -3 2 k g/ m 2; a n d a t otal b o d y wei g ht >4 5 k g ( 1 1 0 l b).
5. 2. E xcl usi o n Criteri a
Partici pa nts are e xcl u de d fr o m t he st u d y  if a n y of t he f oll o wi n g criteria a p pl y:
Me dic al C o n diti o ns:
1.
E vi de nce or hist or y  of cli nicall y si g nifica nt he mat ol o gical, re nal, e n d ocri ne, 
p ul m o nar y , gastr oi ntesti nal, car di o vasc ular, he patic, ps yc hiatric, ne ur ol o gical, or 
aller gic disease (i ncl u di n g dr u g aller gies, b ut e xcl u di n g u ntreate d, asy m pt o matic, 
seas o nal aller gies at t he ti me of d osi n g).

Hist or y  of HI V i nfecti o n, he patitis B, or he patitis C; p ositi ve testi n g f or HI V , 
H Bs A g, or H C V A b. He patitis B vacci nati o n is all o we d.
2.
A n y  me dical or ps yc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past ye ar) or acti ve 
s uici dal i deati o n/be ha vi or or la b orat or y  a b n or malit y or ot her c o n diti o ns t hat ma y 
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.
3.
C o n diti o ns t hat affect a bilit y  t o taste e g, d y s ge usia, res pirat or y i nfecti o n, c ol d, etc.
4.
Hist or y  of hy p erse nsiti vit y t o t he acti ve c o m p o u n ds or t o a n y i nacti ve i n gre die nts 
(e xci pie nts) c o ntai ne d i n t he f or m ulati o ns.
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 p rescri pti o n dr u gs a n d dietar y a n d her bal s u p ple me nts 
wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n, wit h t he e xce pti o n of m o derate/str o n g C Y P 3 A i n d ucers or 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. ( 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).
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 8
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
6.
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). Partici pati o n i n 
st u dies of ot her i n vesti gati o nal pr o d ucts ( dr u g or vacci ne) at a ny ti me d uri n g t heir 
partici pa ti o n i n t his st u d y. 
Di a g n ostic Assess me nts:
7.
A p ositi ve uri ne dr u g test at scree ni n g or a d missi o n . A si n gle re peat f or p ositi ve dr u g 
scree n m a y  be all o we d.
8.
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 /ser u m pre g na nc y  
test i n W O C B P at Da y - 1
9.
Use of t o bacc o/ nic oti ne c o ntai ni n g pr o d ucts , as i n dicate d b y  a p ositi ve uri ne c oti ni ne
test at scree ni n g or a d missi o n.
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 or 
partici pa nts < 6 0 ye ars; a n d ≥1 5 0/ 9 0 m m H g f or partici pa nts ≥6 0 y ears ol d, f oll o wi n g 
at least 5 mi n utes of s u pi ne rest. If s yst olic B P is ≥ 1 4 0 or 1 5 0 m m H g ( base d o n a ge ) 
or diast olic ≥9 0 m m H g, t he B P s h o ul d be re peate d 2 m ore ti mes a n d t he a vera ge of 
t he 3 B P val ues s h o ul d be use d t o deter mi ne t he partici pa nt ’s eli gi bilit y. 
1 1. Re nal i m pair me nt as defi ne d b y  a n eG F R ( u nits of m L/ mi n/ 1. 7 3 m²) 
< 6 0 m L / mi n(/ 1. 7 3 m²). Si nce partici pa nts are 1 8 ye ars a n d a b o ve, 2 0 2 1 C K D- E PI 
e G F R (c o m bi ne d Screat a n d Sc ys) is t he rec o m me n de d f or m ula (see Secti o n 1 0. 6. 2 ) 
t o deter mi ne eli gi bilit y a n d t o pr o vi de a baseli ne t o q ua ntif y a n y s u bse q ue nt ki d ne y 
safety e ve nts.
1 2. St a n dar d 1 2 -lea d E C G t hat de m o nstrates cli nicall y rele vant 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 ocar dial i nfarcti o n, S T-T 
i nter val c ha n ges s u g gesti ve of m yocar dial isc he mia, sec o n d- or t hir d - de gree 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 Q TcF e xcee ds 4 5 0 ms, or 
Q R S e xcee ds 1 2 0 ms, t he E C G s h o ul d be re peate d t wice a n d t he a vera ge of t he 
3 Q Tc F or Q R S val ues use d t o deter mi ne t he partici pa nt’s eli gi bilit y .
C o m p uter -i nter prete d E C Gs s h o ul d be o verrea d by a p h ysicia 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 3. Partici pa nt s 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 nd c o nfir me d b y  a si n gle 
re peat test, if dee me d necessar y: 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 2 9

A L T, A S T, Bili ≥ 1. 0 5 × U L N. Partici pa nts wit h a n ele vate d t otal bilir u bi n 
c o nsiste nt wit h Gil bert’s Disease s h o ul d ha ve a 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 4. 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 5. 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 Lifest yle C o nsi derati o ns 
secti o n of t his pr ot oc ol.
1 6. 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 olve 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. T he i n vesti gat or or desi g nee will a d vise t he partici pa nt t o see k a d vice a b o ut t he 
d o nati o n a n d cr y o preser vati o n of ger m cells pri or t o t he start of st u d y i nter ve nti o n, if 
a p plica ble.
At ti me p oi nts i n dicate d i n S o A , t he i n vesti gat or or desi g nee will i nf or m t he partici pa nt of 
t he nee d t o use hi g 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 
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.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 0
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.

Partici pa nts m ust a bstai n fr o m c he wi n g, br us hi n g/fl ossi n g teet h a n d ri nsi n g t heir 
m o ut h (e xce pt wit h water) f or at least 1 h o ur pri or t o t he palata bilit y assess me nt.

Partici pa nts ma y  ha ve a meal a n d c o ns u me it at least 6 0 mi n utes bef ore t he start of 
t he palata bilit y assess me nt, a n d dri n k water at least 3 0 mi n utes bef ore t he start of t he 
palata bilit y  assess me nt.

W hile partici pa nts are c o nfi ne d, t he ir t otal dail y n utriti o nal c o m p ositi o n s h o ul d be 
a p pr o xi matel y 5 5 % car b o h ydrate, 3 0 % fat , a n d 1 5 % pr otei n. T he dail y cal oric i nta ke 
per partici pa nt s h o ul d n ot e xcee d a p pr o xi matel y 3 2 0 0 kcal.
5. 3. 3. C affei ne a n d Alc o h ol

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 o m pleti o n of t he fi nal palata bilit y  assess me nt. 

Partici pa nt s will a bstai n fr o m alc o h ol f or 2 4 h o urs pri or 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 om pleti o n of t he fi nal palata bilit y  assess me nt . 
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.
5. 3. 4. Acti vit y

Partici pa nts will a bstai n fr o m stre n u o us e xercise (e g, hea v y lifti n g, wei g ht trai ni n g, 
calist he nics, aer o bics) f or at least 4 8 h o urs pri or t o eac h bl o o d c ollecti o n f or cli nical 
la b orat or y tests. Wal ki n g at a n or mal pace will be per mitte d.
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 not 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/a u xiliar y  me dici nal pr o d ucts, me dical de vices, a n d ot her i nter ve nti o ns (e g, s ur gical 
a n d be ha vi oral) i nte n de d t o be a d mi nistere d t o t he st u d y partici pa nts d uri n g t he st u d y 
c o n d uct.
F or t he p ur p oses of t his pr ot oc ol, st u d y i nter ve nti o n refers t o sis u nat o vir.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 1
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) Palata bilit y i n 
Li q ui d Ve hicles
Bitre x
T y pe
Dr u g
E xci pie nt 
Use
E x peri me ntal
F or assess me nt of bitter ness e n d p oi nt
I M P or NI M P/ A x M P
I M P
A x M P
D ose F or m ul ati o n
1 0 0 m g sis u nat o vir (t w o 5 0 m g ca ps ules) dr y 
p o w der ble n d i ncl u de d wit h var yi n g 
e xci pie nts, dis perse d i n 0. 9 % s o di u m c hl ori de 
f or oral R O A
7. 5 μ g d ose i n 1 5 m L water
U nit D ose Stre n gt h(s)
5 0 m g ca ps ule
2 μ g
D os a ge Le vel(s)
R o ute of A d mi nistr ati o n
Oral/ “S wirl a n d S pit”
Oral/ “S wirl a n d S pit”
S o urci n g
Sis u nat o vir: Pr o vi de d ce ntrall y b y t he s p o ns or
 
Stra w berr y fla v o ur & E xci pie nts: 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
P ac k a gi n g a n d L a beli n g
St u d y i nter ve nti o n will be pr o vi de d i n i n 
b ul k. Eac h c o ntai ner will be la bele d as 
re q uire d per c o u ntr y re q uire me nt. C R U Staff 
will pre pare i n di vi d ual d oses (ca ps ule c o nte nt 
+ li q ui d) f or a d mi nistrati o n per E D R.
St u d y i nter v e nti o n will be pr o vi de d i n 
b ul k . Eac h c o ntai ner will be la bele d as 
re q uire d per c o u ntr y re q uire me nt.
S R S D
I B
U S P
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
Bitre x, De nat o ni u m Be nz oate
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)
C CI
C CI


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 2
St u d y Ar m(s)
A r m  Title
Peri o d 1 t o Peri o d 8
A r m  Descri pti o n
Partici pa nts will recei ve st u d y i nter ve nti o n i n a ra n d o mize d cr oss o ver ma n ner at eac h 
peri o d, u p t o 4 ti mes a da y f or Da y 1 a n d Da y 2 .
St u d y  i nter ve nti o n will be s u p plie d b y Pfizer as 5 0-m g ca ps ules .
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.
6. 1. 1. A d mi nistr ati o n
All f or m ulati o ns will be offere d t o all partici pa nts f or tasti n g i n a bli n de d fas hi o n. 
Partici pa nts will taste a p pr o xi matel y  m L of a  
 m g/ m L  s us pe nsi o n of sis u nat o vir, gi ve n 
i n a ra n d o mize d or der. Partici pa nts will s wirl t he sa m ple i n t he m o ut h f or a p pr o xi matel y 1 0 
sec o n ds, a n d t he n s pit it o ut . Partici pa nts will assess vari o us as pects of t he taste usi n g t he 
q uesti o n naire i n A p pe n di x 9 : Oral S ol uti o n or S us pe nsi o n Palata bilit y Q uesti o n naire at 
a p pr o xi matel y 1 mi n ute, 5 mi n utes, 1 0 mi n utes, a n d 2 0 mi n utes after d osi n g . T here will be at 
least 6 0 mi n utes bet wee n tasti n g of eac h st u d y i nter ve nti o n, a n d partici pa nts s h o ul d ri nse 
t heir m o ut h wit h a m bie nt te m perat ure water after c o m pleti o n of t he q uesti o n naire a n d pri or 
t o t he ne xt tasti n g. Dri n ki n g of water t o clea nse palate is all o we d e xce pt wit hi n 3 0 mi n utes t o 
t he start of t he s u bse q ue nt assess me nt, a n d meals ca n be ta ke n a n d c o m plete d at least 6 0 
mi n utes bef ore t he start of a n assess me nt (see Secti o n 5. 3. 2 ).
A d mi nistrati o n of st u d y  i nter ve nti o n(s) at t he site will be perf or me d b y a n a p pr o priatel y 
q ualifie d a n d trai ne d me m ber of t he st u d y staff as all o we d b y l ocal, state, a n d i nstit uti o nal 
g ui da nce. 
F oll o wi n g a d mi nistrati o n of st u d y  i nter ve nti o n(s) at t he site, partici pa nts will be o bser ve d f or 
2 0 mi n utes b y  a n a p pr o priatel y q ualifie d a n d trai ne d me m ber of t he st u d y staff. A p pr o priate 
me dicati o n a n d ot her s u p p orti ve meas ures f or ma na ge me nt of a me dical e mer ge nc y will be 
a vaila ble i n acc or da nce wit h l ocal g ui deli nes a n d i nstit uti o nal g ui deli nes.
6. 2. Pre p ar ati o n , H a n dli n g , St or a ge , a n d Acc o u nt a bilit y
1.
T he i n vesti gat or or desi g nee m ust c o nfir m t hat a p pr o priate c o n diti o ns (e g, 
te m perat ure) ha ve bee n mai ntai ne d d uri n g tra nsit f or all st u d y  i nter ve nti o ns recei ve d 
a n d a n y discre pa ncies are re p orte d a n d res ol ve d bef ore use of t he st u d y i nter ve nti o n. 
2.
O nl y  partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y i nter ve nti o n a n d o nl y 
a ut h orize d site staff ma y  s u p pl y, pre pare, a n d/or a d mi nister st u d y  i nter ve nti o n.
3.
All st u d y  i nter ve nti o ns m ust be st ore d i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d 
m o nit ore d ( ma n ual or a ut o mate d rec or di n g) area i n acc or da nce wit h t he la bele d 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)
C CI
C CI


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 3
st ora ge c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d a ut h orize d site staff. At 
a mi ni m u m, dail y  mi ni m u m a n d ma xi m u m te m perat ures f or all site st ora ge l ocati o ns 
m ust be d oc u me nte d a n d a vaila ble u p o n re q uest. Data f or n o n w or ki n g da y s m ust 
i n dicate t he mi ni m u m a n d ma xi m u m te m perat ures si nce pre vi o usly d oc u me nte d u p o n 
ret ur n t o b usi ness.
4.
A n y  e xc ursi o ns fr o m t he st u d y i nter ve nti o n la bel st ora ge c o n diti o ns s h o ul d be 
re p orte d t o Pfizer u p o n disc o ver y al o 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 nter ve nti o n t o t he la bele d st ora ge c o n diti o ns, 
as s o o n as p ossi ble. O nce a n e xc ursi o n is i de ntifie d, t he st u d y  i nter ve nti o n m ust be 
q uara nti ne d a n d n ot use d u ntil Pfizer pr o vi des per missi o n t o use t he st u d y  
i nter ve nti o n. S pecific details re gar di n g t he e xc ursi o n defi niti o n a n d i nf or mati o n t o
re p ort f or eac h e xc ursi o n will be pr o vi de d t o t he site i n t he P C R U l ocal/site 
pr oce d ures.
5.
A n y  st ora ge c o n diti o ns state d i n t he S R S D will be s u perse de d b y t he st ora ge 
c o n diti o ns state d o n t he la bel.
6.
St u d y  i nter ve nti o ns s h o ul d be st ore d i n t heir ori gi nal c o ntai ners.
7.
T he i n ves ti 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 l ocal pr oce d ure s. 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 nvesti gat or m ust e ns ure t hat t he materials are destr o ye d i n c o m plia nce wit h 
a p plica ble e n vir o n me ntal re g ulati o ns, i nstit uti o nal p olic y , a n d a n y s pecial i nstr ucti o ns 
pr o vi de d b y Pfizer.
U p o n i de ntificati o n of a pr o d uct c o m plai nt, n otif y t he s p o ns or w it hi n 1 b usi ness da y  of 
disc o ver y  as descri be d i n t he E D R .
6. 2. 1. Pre p ar ati o n a n d Dis pe nsi n g
Wit hi n t his pr ot oc ol, pre parati o n refers t o t he i n vesti gat or site acti vities perf or me d t o ma ke 
t he st u d y i nter ve nti o n rea d y f or a d mi nistrati o n or dis pe nsi n g t o t he partici pa nt b y q ualifie d 
staff. Dis pe nsi n g is defi ne d as t he pr o visi o n of st u d y i nter ve nti o n, c o nc o mita nt treat me nts, 
a n d acc o m pa n yi n g i nf or mati o n b y  q ualifie d staff me m ber(s) t o a healt hcare pr o vi der, 
partici pa nt , i n acc or da nce wit h t his pr ot oc ol. Local healt h a ut h orit y re g ulati o ns or 
i n vesti gat or site g ui deli nes ma y use alter nati ve ter ms f or t hese acti vities.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 4
Sis u nat o vir oral d osi n g s us pe nsi o n will be pre pare d i n t he C R U b y  2 o perat ors , 1 of w h o m is 
a p har macist. Details of d ose pre parati o n will be gi ve n i n a se parate E D R . Pre pare d d oses
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 i n vesti gat or site’s la beli n g re q uire me nts.
St u d y  i nter ve nti o n will be pre pare d b y q ualifie d u n bli n de d site pers o n nel acc or di n g t o t he 
E D R . 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 ys icia n, 
n urse, p h ys icia n’s assista nt, n urse practiti o ner, p har mac y assista nt/tec h nicia n, or p har macist). 
6. 3. Assi g n me nt t o St u d y I nter ve nti o n
T he i n vesti gat o r’s k n o wle d ge of t he treat me nt 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 nt s 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 stu d y . Pfizer will pr o vi de a ra n d o mizati o n sc he d ule t o t he i n vesti gat or a n d, i n acc or da nce 
wit h t he ra n d o mizati o n n u m bers, t he partici pa nt will recei ve t he st u d y treat me nt re gi me n 
assi g ne d t o t he c orres p o n di n g ra n d o mizati o n n u m ber.
6. 4. Bli n di n g
T his is a si n gle-bli n d st u d y. 
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 s.
6. 4. 2. Bli n di n g of Site Pers o n nel
I n vesti gat ors a n d ot her site staff will be u n bli n de d t o partici pa nts’ assi g ne d st u d y 
i nter ve nti o n. 
6. 4. 3. Bli n di n g of t he S p o ns o r
S p o ns or staff will be u n bli n de d t o partici pa nts’ assi g ne d st u d y  i nter ve nti o n. 
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 safety assess me nt a n d/ or s u p p orti n g cl i nical 
de vel o p me nt.
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 st u d y i nte r 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 b y a me m ber of t he st u d y site staff .
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 5
Partici pa nts will s wirl t he st u d y i nter ve nti o n i n t heir m o ut h f or a p pr o xi matel y  1 0 sec o n ds a n d 
s pit it o ut. If t he partici pa nt acci de ntall y i n gests t he taste st u d y i nter ve nti o n, he/s he will n ot 
be per mitte d t o c o nti n ue e val uati n g a n y f urt her taste st u d y i nter ve nti o n (s) a n d will be 
wit h dra w n fr o m t he st u d y.
6. 6. D ose M o dific ati o n
N ot a p plica ble.
6. 7. C o nti n ue d Access t o St u d y I nter ve nti o n A fter t he E n d of t he St u d y
N o st u d y i nter ve nti o n will be pr o vi de d t o partici pa nts at t he e n d of t heir st u d y partici pati o n.
6. 8. Tre at me nt of O ver d ose
F or t his st u d y , a n y d ose of sis unat 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.
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 f oll o w u p u ntil res ol uti o n, sta bilizati o n, t he e ve nt is 
ot her wise e x plai ne d, or t he partici pa nt is l ost t o f oll o w -u p (as defi ne d i n Secti o n 7. 3 ).
3.
D oc u me nt t he q ua ntit y of t he e xcess d ose as well as t he d urati o n of t he o ver d ose i n 
t he C R F.
4.
O ver d ose is re p orta ble t o Pfizer Safet y  o nl y w he n ass oci ate d wit h a n S A E.
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y  t he i n vesti gat or i n 
c o ns ultati o n wit h t he st u d y me dical m o nit or as nee de d base d o n t he cli nical e val uati o n of t he 
partici pa nt.
6. 9. Pri or a n d C o nc o mit a nt T her a p y
Use of prescri pti o n or n o n prescri pti o n dr u gs a n d dietar y  a n d her bal s u p ple me nts are 
pr o hi bite d wit hi n 7 da y s or 5 half -li ves ( w hic he ver is l o n ger) pri or t o t he first d ose of st u d y 
i nter ve nti o n e xce pt f or m o derate/str o n g C Y P 3 A i n d ucers or 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 pri or t o t he first d ose of st u d y i nter ve nti o n. Li mite d use of 
n o n prescri pti o n me dicati o ns t hat are n ot belie ve d t o affect partici pa nt safet y  or t he o verall 
res ults of t he st u d y ma y be per mitte d o n a case-b y -case basis f oll o wi n g a p pr o v al 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 d i x 4).
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 6
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 ve 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 uat i o n i n t he i n vesti gat or’s vie w

Pre g na nc y  
If st u d y i nter ve nti o n is per ma ne ntl y 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.
7. 1. 1. P ote nti al C ases of Ac ute Ki d ne y I nj ur y
Partici pa nts e x p ose d t o I M P de m o nstrati n g tra nsie nt or s ustai ne d i ncrease i n Screat ( wit h 
decrease i n Screat - base d e G F R or e Cr Cl) re q uire e x pe dite d e val uati o n t o differe ntiate A KI 
fr o m DI CI. DI CI is defi ne d as tra ns p orter- me diate d effect relate d t o altere d re nal t u b ular 
creati ni ne ha n dli n g wit h o ut hist ol o gical i nj ur y .
A KI m a y  be d ue t o o ne or m ore ty pes of i nj ur y, i ncl u di n g DI KI. Differe ntiati o n of DI KI 
fr o m ot her ca uses of A KI a n d fr o m DI CI ma y re q uire cli nical, ra di o gra p hic, hist o pat h ol o gic, 
a n d la b orat or y assess me nts, as well as ne p hr ol o g y c o ns ultati o n.
F oll o w -u p Assess me nts
T he partici pa nt s h o ul d ret ur n t o t he site f or e val uati o n as s o o n as p ossi ble, prefera bl y wit hi n 
4 8 h o urs of a ware ness of t he a b n or mal res ults. 
E val uati o n s h o ul d i ncl u de p h y sical e xa mi nati o n, la b orat or y tests, detaile d me dical a n d 
s ur gical hist or y, re vie w of all me dicati o ns (i ncl u di n g recreati o nal dr u gs a n d s u p ple me nts 
[ her bal]), fa mil y hist or y, se x ual hist or y, tra vel hist or y, bl o o d tra nsf usi o n, a n d p ote ntial 
occ u pati o nal e x p os ure t o c he micals. 
La b orat or y  assess me nts s h o ul d i ncl u de si m ulta ne o us ser u m c ystati n C ( Sc ys) a n d ser u m 
creati ni ne ( Screat) tests. Esti mates of e G F R, e Cr Cl a n d Screat -base d e G F R a n d c o m bi ne d 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 7
Screa t-S c y s-base d e G F R s h o ul d als o be deri ve d usi n g t he a p pr o priate e q uati o n descri be d i n 
A p pe n di x 6 .
Assess me nts of uri ne al b u mi n -t o-creati ni ne rati o or uri ne v ol u me ma y  als o be perf or me d as 
a p pr o priate.
If a p pr o priate, ne p hr ol o g y c o ns ultati o n ma y be rec o m me n de d t o facilitate differe ntiati o n of 
re nal pare nc hy m al disease, pre-re nal az ote mia, a n d p ost-re nal o bstr ucti o n. 
Differe nti ati n g Ac ute Ki d ne y I nj ur y fr o m DI CI
A c o nfir me d Screat i ncrease is defi ne d as:
(i) ≥0. 3 m g/ d L ( ≥2 6. 5 µ m ol/ L) wit hi n 4 8 h o urs O R 
(ii) c o nfir me d Screat i ncrease ≥1. 5 ti mes baseli ne ( k n o w n or s us pecte d t o ha ve occ urre d 
wit hi n t he pri or 7 da y s). 
Base d o n t he assess me nts perf or me d, s us pecte d A KI (i ncl u di n g DI KI) ma y be differe ntiate d 
fr o m DI CI as f oll o ws.
A d ult p artici p a nts
A KI (i ncl u di n g DI KI)
A n y o ne of t he bel o w
DI CI
Sc ys & Screat
Si m ulta ne o us, c o nfir me d ser u m c ystati n 
C ( Sc ys) i ncrease a n d c o nfir me d Screat 
i ncrease 
C o nfir me d Screat i ncrease wit h o ut 
c o nfir me d i ncrease i n refle x Sc ys 
A N D 
C o nfir me d Screat -base d e G F R 
decrease w it h o ut c o nfir me d c o m bi ne d 
Screat -Sc ys -base d e G F R decrease.
e G F R
Decrease i n Screat -base d e G F R a n d 
c o m bi ne d Screat -Sc ys -base d e G F R ( w he n 
a vaila ble)
Al b u mi n uria or 
pr otei n uria
C o nfir me d al b u mi n uria i ncrease (see 
A p pe n di x 6 f or Gra des A 1 t o A 3 
q ua ntitati o n)
Uri ne v ol u me
Uri ne v ol u me < 0. 5 m L/ k g/ h f or 6 
c o nsec uti ve h o urs
Re gar dless of t he prese nce or a bse nce of i ncrease i n Screat, DI KI a n d ot her ca uses of A KI 
ma y  be s us pecte d if eit her t here is (i) ne w-o nset or w orse ni n g al b u mi n uria or pr otei n uria are 
detecte d or (ii) uri ne v ol u me (if meas ure d) is < 0. 5 m L / k g/ h f or 6 c o nsec uti ve h o urs).
All c o nfir me d cases of cli nicall y rele va nt decrease i n ki d ne y f u ncti o n s h o ul d be c o nsi dere d 
p ote ntial cases of DI KI if n o ot her reas o n f or t he ki d ne y  f u ncti o n a b n or malities has bee n 
f o u n d.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 8
7. 1. 2. C O VI D - 1 9
If a partici pa nt has C O VI D-1 9 d uri n g t he st u d y, t his s h o ul d be re p orte d as a n A E or S A E (as 
a p pr o priate) a n d a p pr o priate me dical i nter ve nti o n pr o vi de d. Te m p orar y  or per ma ne nt 
disc o nti n uati o n of t he st u d y  i nter ve nti o n ma y be a p pr o priate. 
It is rec o m me n de d t hat t he i n vesti gat or disc uss te m p orar y or per ma ne nt disc o nti n uati o n of 
st u d y i nter ve nti o n wit h t he st u d y me dical m o nit or. 
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 early 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 ea rl 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 an d n otif y  t he s p o ns or acc or di n gl y.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt (see Secti o n 7. 2. 1 f or 
discl os ure of f ut ure i nf or mati o n, n o f urt her e val uati o ns will be perf or me d a n d n o a d diti o nal 
data 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 n y  data c ollecte d bef ore 
s uc h wit h dra wal of c o nse nt.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 3 9
7. 2. 1. Wit h dr a w al of C o nse nt 
Partici pa nt s wh 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 co ntact 
wit h t he m or pers o ns pre vi o usl y  a ut h orize d b y t he partici pa nt t o pr o vi de t his i nf or mati o n. 
Partici pa nt s s h o ul d n otif y t he i n vesti gat or i n writi n g of t he decisi o n t o wit h dra w c o nse nt 
fr o m f ut ure f oll o w- u p, w he ne ver p ossi ble. T he wit h dra wal of c o nse nt s h o ul d be e x plai ne d i n 
detail i n t he me dical rec or ds b y t he i n vesti gat or, as t o w het her t he wit h dra wal is o nl y  fr o m 
f urt her recei pt of st u d y i nter ve nti o n or als o fr o m st u d y  pr oce d ures a n d/ or p osttreat me nt st u d y 
f oll o w- u p, a n d e ntere d o n t he a p pr o priate C RF 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 -U p 
A p artici 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 atte n d a re q uire d st u d y visit:

T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d visit as 
s o o n as p ossi ble. Co u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d ascertai n w het her t he partici pa nt wis hes t o a n d/ or s h o ul d 
c o nti n ue i n t he st u d y;

Bef ore a parti ci pa nt is dee me d l ost t o f oll o w - u p, t he i n vesti gat or or desi g nee m ust 
ma ke e ver y  eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n maili n g 
a d dress or l ocal e q ui vale nt met h o ds). T hese c o 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 ud 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 Pr oce d ures
T he i n vesti gat or ( or a n a p pr o priate dele gate at t he i n vesti gat or site) m ust o btai n a si g ne d a n d 
date d I C D bef ore perf or mi n g a n y st u d y- s pecific pr oce d ures. 
St u d y  pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A . Pr ot oc ol wai vers or 
e xe m pti o ns are n ot all o we d.
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A , is esse ntial 
a n d req uire d f or st u d y  c o n d uct.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 0
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y  criteria. T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c onfir 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 mi nistrati 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/ gr o u p 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 this 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  n ot nee d t o be re peate d, 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.
F or sa m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d 
s hi p me nt i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vestigat 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 partici pa nt s i n t his st u d y is a p pr o xi matel y 
3 5 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 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 n y peri o d of 5 6 c o nsec uti ve da ys.
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 
Life st yle C o nsi derati o ns a n d C o nc o mita nt T hera p y secti o ns of t he pr ot oc ol.
8. 1. 1. B aseli ne Pr oce d ures 
Pla n ne d ti me p oi nts f or me dical hist or y  a n d de m o gra p hy are pr o vi de d i n t he S o A .
8. 2. Effic ac y Assess me nts
Efficac y  is n ot e val uate d i n t his st u d y . 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 1
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 mu 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 o cal re g ulati o n. 
Hei g ht a n d wei g ht will als o be meas ure d a n d rec or de d as per t he S o A . F or meas uri n g wei g ht, 
a scale wit h a p pr o priate ra n ge a n d res ol uti o n is use d a n d m ust be place d o n a sta ble, flat 
s urface. Partici pa nt s m ust re m o ve s h oes, b ul k y la yers of cl ot hi n g, a n d jac kets s o t hat o nl y 
li g ht cl ot hi n g re mai ns. T he y m ust als o re m o ve t he c o nte nts of t heir p oc kets a n d re mai n still 
d uri n g meas ure me nt of wei g ht. 
P h y sical 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 dered s o urce rec or d 
a n d will n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. A n y u nt o war d p h ys ical 
e xa mi nati o n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d meet t he 
defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he pr ocesses i n 
Secti o ns 8. 4. 1 t o 8. 4. 3 .
8. 3. 2. Vit al Si g ns
8. 3. 2. 1. Bl o o d Press ure a n d P ulse R ate
S u pi ne B P will be meas ure d wit h t he partici pa nt ’s ar m s u p p orte d at t he le vel of t he heart, a n d 
rec or de d t o t he nearest m m H g after a p pr o xi matel y 5 mi n utes of rest . T he sa me ar m 
( prefera bly t he d o mi na nt ar m) will be use d t hr o u g h o ut t he st u d y. 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 ra te 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.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 2
A n y  u nt o war d vital si g n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d 
meet t he defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he 
pr ocesses i n Secti o ns 8. 4. 1 t o 8. 4. 3 .
8. 3. 3. Electr oc ar di o gr a ms
Sta n dar d 1 2-l ea d EC Gs will be c ollecte d at ti mes s pecifie d i n t he S o A secti o n of t his
pr ot oc ol usi n g a n E C G s yste m t hat a ut o maticall y calc ulates t he H R a n d meas ures P R, Q T, 
Q Tc F, a n d Q R S i nter vals. 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 uietly f or at least 5 mi n utes i n a s u pi ne p ositi o n. 
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) a 
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 2 a d diti o nal E C Gs will be c ollecte d a p pr o xi matel y  2 t o 4 mi n utes a part t o c o nfir m t he 
ori gi nal meas ure me nt. If t he Q TcF val ues fr o m t hese re peate d E C Gs re mai n a b o ve t he 
t hres h ol d val ue, t he n a si n gle E C G m ust be re peate d at least h o urly u ntil Q Tc val ues fr o m 
2 s uccessi ve E C Gs fall bel o w t he t hres h ol d val ue t hat tri g gere d t he re peat meas ure me nt.
If a) a p ost d ose Q Tc F i nter val re mai ns ≥6 0 ms fr o m t he baseli ne a n d is > 4 5 0 ms ; or b) a n 
a bs ol ute Q T val ue is ≥5 0 0 ms f or a 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 un der g o c o nti n u o us E C G m o nit ori n g. A car di ol o gist s h o ul d be c o ns ulte d if Q Tc F
val ues d o n ot ret ur n t o less t ha n t he criteria liste d a b o ve after 8 h o urs of m o nit ori n g ( or 
s o o ner, at t he discreti o n of t he i n vesti gat or).
I n s o me cases, it ma y be a p pr o priate t o re peat a b n or mal E C Gs t o r ule o ut i m pr o per lea d 
place me nt as c o ntri b uti n g t o t he E C G a b n or malit y. It is i m p orta nt t hat lea ds be place d i n t he 
sa me p ositi o ns eac h ti me i n or der t o ac hie ve precise E C G rec or di n gs. If a mac hi ne-rea d Q Tc 
val ue is pr ol o n ge d, as defi ne d a b o ve, re peat meas ure me nts ma y  n ot be necessar y if a 
q ualifie d me dical pr o 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 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 borat 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 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 3
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 a n d t he s p o ns or n otifie d.
See A p pe n di x 5 f or s u g geste d acti o ns a n d f oll o w- u p assess me nts i n t he e ve nt of p ote ntial 
DI LI .
See A p pe n di x 6 f or i nstr ucti o ns f or la b orat or y testi n g t o m o nit or ki d ne y f u ncti o n a n d 
re p orti n g la b orat or y test a b n or malities.
Partici pa nt s ma y u n der g o ra n d o m uri ne dr u g testi n g at t he discreti o n of t he i n vesti gat or.
Dr u g testi n g c o n d ucte d pri or t o d osi n g m us t be ne gati ve f or partici pa nt s t o recei ve st u d y 
i nter ve nti o n. 
8. 3. 5. Pre g n a nc y Testi n g
A 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 ser u m tests, a n d m ust ha ve a se nsiti vit y  of at least 2 5 mI U/ m L. Pre g na nc y  tests will be 
perf or me d i n W O C B P at t he ti mes liste d i n t he S o A . F oll o wi n g a ne gati ve pre g na nc y test 
res ult at scree ni n g, a p pr o priate c o ntrace pti o n m ust be c o m me nce d a n d a sec o n d ne gati ve 
pre g na nc y  test res ult will be re q uire d at t he baseli ne visit pri or t o starti n g t he st u d y 
i nter ve nti o n. Pre g na nc y tests will als o be d o ne w he ne ver 1 me nstr ual c ycle is misse d d uri n g 
t he acti ve treat me nt peri o d ( or w he n p ote ntial pre g na nc y is ot her wise s us pecte d) a n d at t he 
e n d of t he st u d y. Pre g na nc y tests ma y als o be re peate d if re q ueste d b y IR Bs/ E C s or if 
re q uire d by l ocal re g ulati o ns. If a uri ne test ca n n ot be c o nfir me d as ne gati ve (e g, a n 
a m bi g u o us res ult), a ser u m pre g na nc y  test is re q uire d. I n s uc h cases, t he partici pa nt m ust be
e xcl u de d if t he ser u m pre g na nc y  res ult is p ositi ve.
8. 4. A d verse E ve nts , Seri o us A d verse E ve nts , a n d Ot her S afet y Re p orti n g
T he defi niti o ns of a n A E a n d a n S A E ca n be f o u n d i n A p pe n di x 3 .
A E s ma y arise fr o m sy m pt o ms or ot her c o m plai nts re p orte d t o t he i n vesti gat or b y  t he 
partici pa nt ( or, w he n a p pr o priate, b y a care gi ver, s urr o gate, or t he partici pa nt ’s le gall y 
a ut h orize d re prese ntati ve), or t he y  ma y arise fr o m cli nical fi n di n gs of t he in vesti gat or or 
ot her healt hcare pr o vi ders (cli nical si g ns, test res ults, etc).
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble t o p urs ue 
a n d o btai n a de q uate i nf or mati o n b ot h t o deter mi ne t he o utc o me a n d t o assess w het her t he 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 4
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 nti n ue 
t he st u d y i nter ve nti o n (see Secti o n 7. 1 ). 
D uri n g t he acti ve c ollecti o n peri o d as descri be d i n Secti o n 8. 4. 1, e ac h partici pa nt will be 
q uest i o ne d a b o ut t he occ urre nce of AE 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 ng 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, e xce pt as i n dicate d 
bel o w , 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 the 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, t he A E or S A E m ust be rec or de d o n t he C R F a n d t he S A E 
re p orte d usi n g t he C T S A E Re p ort F or m.
I n vesti gat ors are n ot o bli gate d t o acti vely see k i nf or mati o n o n A Es or S A E s after t he 
partici pa nt has c o ncl u de d st u d y partici pati o n. H o 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.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 5
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 .
All n o nseri o us A Es lea di n g t o per ma ne nt disc o nti n uati o n of st u d y  i nter ve nti o n a n d S A Es ( or 
a d diti o nal A Es as re q uire d b y  re g ulat or y a ut h orities) 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 Es lea di n g t o per ma ne nt disc o nti n uati o n of st u d y  i nter ve nti o n a n d S A Es re p orte d by t he 
partici pa nts t hat meet t he a b o ve criteria.
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 lea di n g t o 
per ma ne nt disc o nti n uati o n of st u d y  i nter ve nti o n t hat is deter mi ne d b y t he s p o ns or t o be 
seri o us will be re p orte d b y t he s p o ns or as a n S A E. T o assist i n t he deter mi nati o n of case 
seri o us ness, f urt her i nf or mati o n ma y be re q ueste d fr o m t he i n vesti gat or t o pr o vi de clarity 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 .
If a partici pa nt be gi ns a ne w t hera py, t he rec or di n g peri o d f or n o nseri o us A Es lea di n g t o 
per ma ne nt disc o nti n uati o n of st u d y  i nter ve nti o n e n ds at t he ti me t he ne w treat me nt is starte d; 
h o we ver, S A Es m ust c o nti n ue t o be rec or de d o n t he C R F d uri n g t he a b o ve -i n dicate d acti ve 
c ollecti o n peri o d. A s witc h t o a c o m merciall y a vaila ble versi o n of t he st u d y i nter ve nti o n is 
c o nsi dere d as a ne w t hera p y f or t he p ur p oses of S A E re p orti n g
Re p orti n g of A Es lea di n g t o per ma ne nt disc o nti n uati o n of st u d y  i nter ve nti o n a n d S A Es f or 
partici pa nts w h o fail scree ni n g a re 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 di 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 .
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 6
Care will be ta ke n n ot t o i ntr o d uce bias w he n detecti n g A E s a n d/ or S A Es. O pe n -e n de d a n d 
n o nlea di n g ver bal q uesti o ni n g of t he partici pa nt is t he preferre d met h o d t o i n q uire a b o ut 
A E occ urre nces.
8. 4. 3. F oll o w - Up of A E s a n d S A Es
After t he i nitial A E or S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y  f oll o w eac h 
partici pa nt at s u bse q ue nt visits/c o ntacts. F or eac h e ve nt, t he i n vesti gat or m ust p urs ue a n d 
o btai n a de q uate i nf or mati o n u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, 
or t he partici pa nt is l ost t o f oll o w- u p (as defi ne d i n Secti o n 7. 3 ).
I n ge neral, f oll o w- u p i nf or mati o n will i ncl u de a descri pti o n of t he e ve nt i n s ufficie nt detail t o 
all o w f or a c o m plete me dical assess me nt of t he case a n d i n de pe n de nt deter mi nati o n of 
p ossi ble ca usalit y . A ny i nf or m ati 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 
a n 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 o m 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 SA 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 vi ders, fa mil y 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 ness.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 7
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.

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. 

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  usi n g t he C T S A E Re p ort F or m re gar dless of w het her a n 
S A E has occ urre d. Details of t he pre g na nc y  will be c ollecte d after t he start of st u d y 
i nter ve nti o n a n d u ntil at least 5 ter mi nal half-li ves after t he last d ose.

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. Si nce t he e x p os ure 
i nf or mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n t he st u d y, t he i nf or mati o n is 
n ot rec or de d o n a C R F; h o we ver, a c o p y of t he c o m plete d re p ort is mai ntai ne d i n t he 
i n vesti gat or site file.
F oll o w -u p is c o n d ucte d t o o btai n ge neral i nf or mati o n o n t he pre g na nc y  a n d its o utc o me f or 
all E D P re p orts wit h a n u n k n o w n o utc o me. T he i n vesti gat or will f oll o w t he pre g na nc y  u ntil 
c o m pleti o n ( or u ntil pre g na nc y  ter mi nati o n) a n d n otif y Pfizer Safety of t he o utc o me as a 
f oll o w-u p t o t he i nitial re p ort. In t he case of a li ve birt h, t he str uct ural i nte grit y  of t he ne o nate 
ca n be assesse d at t he ti me of birt h. I n t he e ve nt of a ter mi nati o n, t he reas o n(s) f or 
ter mi nati o n s h o ul d be s pecifie d a n d, if cli nically p ossi ble, t he str uct ural i nte grit y of t he 
ter mi nate d fet us s h o ul d be assesse d by gr oss vis ual i ns pecti o n ( u n less pre-pr oce d ure test 
fi n di n gs are c o ncl usi ve f or a c o n ge nital a n o maly a n d t he fi n di n gs are re p orte d).
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 8
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 natal deat h, or c o n ge nital a n o mal y i n a li ve -b or n ba b y, a ter mi nate d fet us, a n 
i ntra uteri ne fetal de mise, or a ne o natal deat h), t he i n vesti gat or s h o ul d f oll o w t he pr oce d ures 
f or re p orti n g S A Es. A d diti o nal i nf or mati o n a b out 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 by t he s p o ns or. F urt her 
f oll o w- u p of birt h o utc o mes will be ha n dle d o n a case-b y -case basis (e g, f oll o w- u p o n 
preter m i nfa nts t o i de ntif y de vel o p me ntal dela y s). In t he case of pater nal e x p os ure, t he 
i n vesti gat or will pr o vi de t he partici 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 Br e 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 Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nf or mati o n m ust be re p o rte d 
usi n g t he C T S A E Re p ort F or m . W he n E D B occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, 
t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n t he st u d y, s o t he 
i nf or mati o n is n ot rec or de d o n a C R F. H o we ver, a c o p y  of t he c o m plete d re p ort is 
mai ntai ne d i n t he i n vesti gat or site file.
A n E D B re p ort is n ot create d w he n a Pfizer dr u g s pecifically a p pr o ve d f or use i n 
breastfee di n g w o me n (e g, vita mi ns) is a d mi nistere d i n acc or d a nce wit h a ut h orize d use. 
H o we ver, if t he i nfa nt e x perie nces a n S A E ass ociate d wit h s uc h a dr u g, t he S A E is re p orte d 
t o get her wit h t he E D B .
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 4 9
8. 4. 5. 3. Occ u p ati o n al E x p os ure
T he i n vesti gat or m ust re p ort a n y i nsta nce of occ u pati o nal e x p os ure t o Pfizer Safety wit hi n 2 4 
h o urs of t he i n vesti gat or’s a ware ness usi n g t he C T S A E Re p ort F o r m re gar dless of w het her 
t here is a n ass ociate d S A E. Si nce t he i nf or mati o n a b o ut t he occ u pati o nal e x p os ure d oes n ot 
pertai n t o a partici pa nt e nr olle d i n t he st u d y, t he i nf or mati o n is n ot rec or de d o n a C R F; 
h o we ver, a c o p y of t he c o m plete d re p ort is mai ntai ne d i n t he i n vesti gat or site file .
8. 4. 6. C ar di o v asc ul ar a n d De at h E ve nts
T his secti o n is 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
T his secti o n is n ot a p plica ble.
8. 4. 8. A d verse E ve nts of S peci al I nterest
T his secti o n is 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
T his secti o n is n ot a p plica ble beca use t here are n o me dical de vices i ncl u de d i n t he st u d y .
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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 0
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.
W het her or n ot t he me dicati o n err or is acc o m pa nie d b y  a n A E, as deter mi ne d b y t he 
i n vesti gat or, suc h me dicati o n err ors occ urri n g t o a st u d y  partici pa nt are rec or de d o n t he 
me dicati o n err or pa ge of t he C R F, w hic h is a s pecific versi o n of t he A E pa ge a n d, if 
a p plica ble, a n y ass ociate d seri o us a n d n o nseri o us A E(s), are rec or de d o n t he A E pa ge of t he 
C R F .
I n t he e ve nt of a me dicati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d wit hi n 2 4 h o urs .
Me dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y wit hi n 2 4
h o urs o n a C T S A E Re p ort 
F or m o nl y w he n ass oci ate d wit h a n S A E.
8. 5. P h ar m ac o ki netics 
P har mac o ki netic para meters are n ot e val uate d i n t his st u d y . 
8. 6. Ge netics
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.
8. 1 0. P al at a bilit y assess me nt 
Partici pa nts will s wirl t he sa m ple i n t he m o ut h f or a p pr o xi matel y  1 0 sec o n ds, a n d t he n s pit it 
o ut. Partici pa nts will assess vari o us as pects of t he taste, i ncl u di n g m o ut h feel, bitter ness, 
s weet ness, s o ur ness, salti ness, t o n g ue/ m o ut h b ur n a n d o verall li ki n g, usi n g t he q uesti o n naire 
i n A p pe n di x 9 : Oral S ol uti o n or S us pe nsi o n Palata bilit y  Q uesti o n naire at a p pr o xi matel y 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 1
1 mi n ute, 5 mi n utes, 1 0 mi n utes, a n d 2 0 mi n utes after d osi n g . Details o n st u d y  i nter ve nti o n 
a d mi nistrati o n a n d restricti o ns are pr o vi de d i n Secti o n s 6. 1. 1 a n d 5. 3. 2 .
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 f urt her detaile d i n t he S A P, w hic h will be mai ntai ne d b y  t he s p o ns or. 
T he S A P ma y  m o dif y w hat is o utli ne d i n t he pr ot oc ol w here a p pr o priate; h o we ver, a n y  maj or 
m o dificati o ns of t he pri mar y  e n d p oi nt defi niti o ns or t heir a nalys es will als o be reflecte d i n a 
pr ot oc ol a me n d me nt.
9. 1. St atistic al H y p ot hesis/ H y p ot heses
N o statistical h y p ot hesis will be teste d i n t his st u d y . 
9. 2. A n al ysis Sets
F or p ur p oses of a nal ysis, t he f oll o wi n g a nal ys is sets are defi ne d:
P artici p a nt A n al ysis 
Set
Descri pti o n
E nr olle d 
“E nr olle d ” mea ns a partici pa nt ’s a gree me nt t o partici pate i n a 
cli nical st u d y f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt 
pr ocess a n d ra n d o mizati o n t o st u d y i nter ve nti o n. A partici pa nt 
will be c o nsi dere d e nr olle d if t he i nf or me d c o nse nt is n ot 
wit h dra w n pri or t o partici pati n g i n a n y  st u d y acti vit y after 
scree ni n g. P ote ntial partici pa nts w h o are scree ne d f or t he 
p ur p ose of deter mi ni n g eli gi bilit y  f or t he st u dy , b ut d o n ot 
partici pate i n t he st u d y, are n ot c o nsi dere d e nr olle d, u nless 
ot her wise s pecifie d b y t he pr ot oc ol.
E val ua ble a nal ysis set
All partici pa nts w h o ta ke at least 1 d ose of st u d y i nter ve nti o n
a n d pr o vi de at least 1 c orres p o n di n g assess me nt t o t he 
Palata bilit y  Q uesti o n naire. 
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 e rf or me d a n d will 
descri be t he a nal ys es a n d pr oce d ures f or acc o u nti n g f or missi n g, u n use d, a n d s p uri o us data.
T his secti o n is a s u m mar y of t he pla n ne d statistical a nal yses of t he pri m ar 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 Statistical A nal ysis Pla n. All treat me nt ar ms 
will be re p orte d se paratel y . 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 2
9. 3. 2. Pri m ar y E n d p oi nt(s) A n al ysis
T he data c ollecte d f or palata bilit y  assess me nt usi n g t he s p o ns or -pr o vi de d palata bilit y  
q uesti o n naire will be n u mericall y deri ve d b y meas uri n g le n gt h ( usi n g a scale wit h gra dati o ns 
of at least 0. 1 c m) of t he “ x” mar ke d b y t he partici pa nt relati ve t o t he “ g o o d trait”. F or 
palata bilit y  assess me nt, t he data use d i n t he a nal ysis will be tra nscri be d a n d rescale d t o a 
sc ore fr o m 0 t o 1 0 0 fr o m t he ra w meas ure me nts o n t he q uesti o n naire. T he palata bilit y 
attri b utes ( m o ut h feel, bitter ness, s weet ness, s o ur ness, salti ness, t o n g ue/ m o ut h b ur n, o verall 
li ki n g) fr o m t he palata bilit y q uesti o n naire (A p pe n di x 9 ) will be liste d a n d descri pti vely 
s u m marize d b y  sessi o n a n d ti me p oi nts usi n g eval ua ble a nal ys is set. Ap pr o priate pl ots ma y  
be g e nerate d , s uc h as ra dar pl ots a n d b o x pl ots.
9. 3. 3. Sec o n d ar y E n d p oi nt(s) A n al ysis
All safet y a nal ys es will be perf or me d o n t he safet y p o p ulati o n.
A E s, E C Gs, B P , p ulse rate , a n d safet y la b orat or y data will be re vie we d a n d s u m marize d o n 
a n o n g oi n g basis d uri n g t he st u d y t o e val uate t he safety of partici pa nt s. A ny cli nical 
la b orat or y, E C G, B P, a n d p ulse rate a b n or malities of p ote ntial cli nical c o ncer n will be 
descri be d. Safet y data will be prese nte d i n ta b ular a n d/ or gra p hical f or mat a n d s u m marize d 
descri pti vel y, w here a p pr o priate.
Me dical hist or y  a n d p h ysical e xa mi nati o n a n d ne ur ol o gical e xa mi nati o n i nf or mati o n, as 
a p plica ble, c ollecte d d uri n g t he c o urse of t he st u d y, will be c o nsi dere d s o urce data a n d will 
n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. H o we ver, a n y u nt o war d fi n di n gs 
i de ntifie d o n p h ysical a n d/ or ne ur ol o gical e xa mi nati o ns c o n d ucte d duri 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 vital si g ns, will be c o nsi dere d s o urce data, a n d will n ot be re q uire d t o be 
re p orte d, u nless ot her wise n ote d. De m o gra p hic data c ollecte d at scree ni n g will be re p orte d.
T he n u m ber ( %) of partici pa 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 fr o m baseli ne i n t he f oll o wi n g cate g ories will be ta b ulate d: 
S afet y Q Tc F Assess me nt
De gree of Pr ol o n g ati o n
Mil d ( ms)
M o der ate ( ms)
Se vere ( m s)
A bs ol ute val ue
> 4 5 0 -4 8 0
> 4 8 0 -5 0 0
> 5 0 0
I ncrease fr o m baseli ne
3 0 -6 0
> 6 0
9. 4. I nteri m A n al yses
N o i nteri m a nalys is will be c o n d ucte d f or t his st u d y.
9. 5. S a m ple Size Deter mi n ati o n
A s ufficie nt n u m ber of partici pa nts will be scree ne d t o ac hie ve 1 2 partici pa nts ra n d o mize d t o 
st u d y i nter ve nti o ns. T he sa m ple size is e m piricall y  selecte d a n d is n ot base d o n statistical 
p o wer calc ulati o n. 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 3
Wit h a sa m ple size of 1 2 partici pa nts, t he e x pecte d half -wi dt h of 2- si de d 9 0 % C Is of t he 
esti mate d mea n sc ore f or eac h palata bilit y assess me nt wit h 8 0 % pr o ba bilit y  c o vera ge are 
s h o w n bel o w. T he S Ds were o btai ne d fr o m t he Bitre x gr o u p of st u d y B 7 9 8 1 0 2 1.
P al at a bilit y assess me nt
S D
H alf -Wi dt h of t he 9 0 % CI wit h 8 0 % c o ver a ge
Bitter ness
1 8. 0 
1 0. 8
M o ut h Feel
2 6. 0 
1 5. 5
O verall Li ki n g
2 2. 7 
1 3. 6
Salti ness
2 4. 4 
1 4. 6
S o ur ness
2 3. 5 
1 4. 0
T o n g ue / M o ut h B ur n
1 7. 7 
1 0. 6
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 4
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 ne s, 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 I R B/ E C a p pr o val bef ore im 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 pri or t o i nitiati o n e xce pt f or c ha n ges necessar y  t o eli mi nate a n i m me diate hazar d t o 
st u d y partici pa nts.
T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:

Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y  t o t he I R B/ E C a n 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 a c hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y a n a p plica ble 
re g ulat or y a ut h ority i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of t he st u d y 
i nter ve nti o n, Pfizer s h o ul d be i nf or me d i m me diatel y.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 5
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 st u d y partici pa nt s a gai nst a ny i m me diate hazar d, a n d 
of a n y seri o us breac hes of t his pr ot oc ol or of t he I C H G C P g ui deli nes t hat t he i n vesti gat or 
bec o mes a ware of.
1 0. 1. 2. 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 trial.
Partici pa nt s 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 uire me 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 or s 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 s i g n t he I CD.
Partici pa nts m ust be rec o nse nte d t o t he m ost c urre nt versi o n of t he I R B/ E C-a p pr o ve d I CD (s) 
d uri n g t heir partici pati o n i n t he st u d y as re q uire d per l ocal re g ulati o ns.
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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 6
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 S O Ps o n h o w t o res p o n d i n t he e ve nt of u na ut h orize d access, use, or 
discl os ure of s p o ns or i nf or mati o n or s y ste ms.
1 0. 1. 3. 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. 4. Disse mi n ati o n of Cli nic al St u d y D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y res ults t hr o u g h p osti n g t he 
res ults of st u dies o n w w w.cli nicaltrials . g o v ( Cli nical Trials. g o v), t he E u dra C T/ C TIS , a n d/ or 
w w w. pfizer .c o m, a n d ot her p u blic re gistries a n d we bsites i n acc or da nce wit h a p plica ble l ocal 
la ws/re g ulati o ns. I n a d diti o n, Pfizer re p orts st u d y res ults o utsi de of t he re q uire me nts of l ocal 
la ws/re g ulati o ns p urs ua nt t o its S O Ps.
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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 7
w w w.cli nicaltrials . g o v
Pfizer p osts cli nical trial res ults o n w w w.cli nicaltrials. g o v f or Pfizer- s p o ns ore d i nter ve nti o nal 
st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safet y a n d/ or efficac y of a 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 d me nts, sa m ple C R Fs, a n d S A P s. Cli nical 
d oc u me nts will ha ve pers o nall y  i de ntifia ble i nf or mati o n a n o n ymize d.
Data shari n g
Pfizer pr o vi des researc hers sec ure access t o partici pa nt -le vel data or f ull C S Rs f or t he 
p ur p oses of “ b o na -fi de scie ntific researc h” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of 
t he disease, tar get, or c o m p o u n d class. Pfizer will ma ke data fr o m t hese trials a vaila ble 
1 8 m o nt hs after st u d y  c o m pleti o n. Partici pa nt -le vel data will be a n o ny m ize d i n acc or da nce 
wit h a p plica ble pri vac y  la ws a n d re g ulati o ns. C S Rs will ha ve pers o nall y 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 yses. Researc h tea ms m ust i ncl u de a bi ostatisticia n. Data will n ot 
be pr o vi de d t o a p plica nts wit h si g nifica nt c o 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. 5. D at a Q u alit y Ass ur a nce
All partici pa nt data relati n g t o t he st u d y will be rec or de d o n pri nte d or electr o nic C R F u nles s 
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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 8
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 d y c o m pleti o n. It is i m p orta nt t hat t he 
i n vesti gat or(s) a n d t heir rele va nt pers o n nel are a vaila ble d uri n g t he m o nit ori n g visits a n d 
p ossi ble a u dits or i ns pecti o ns a n d t hat s ufficie nt ti me is de v ote d t o t he pr ocess .
M o nit ori n g details descri bi n g strate g y , i ncl u di n g defi niti o n of st u d y-critical data ite ms a n d 
pr ocesses (e g, ris k-base d i nitiati ves i n o perati o ns a n d q ualit y , s uc h as ris k m a na ge me nt a n d 
m iti gati o n strate gies a n d anal yt ical ris k- base d m o nit ori n g), met h o d s, res p o nsi bilities, a n d 
re q uire me nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d m o nit ori n g tec h ni q ues 
(ce ntral, virt ual , or o n-site m o nit ori n g), are pr o vi de d i n t he data ma na ge me nt pla n a n d 
m o nit ori n g pla n mai ntai ne d a n d utilize d b y  t he s p o ns or or desi g nee.
T he s p o ns or or desi g nee is res p o nsi ble f or t he data ma na ge me nt of t his st u d y , i ncl u di n g 
q ualit y  c hec ki n g of t he data.
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C D s, pertai ni n g t o t he c o n d uct of t his st u d y m ust 
be retai ne d b y t he i n vesti gat or f or 1 5 ye ars after st u d y c o m pleti o n u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y be destr o ye d d uri n g 
t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he s p o ns or. N o rec or ds ma y  be 
tra nsferre d t o a n ot her l ocati o n or party wit h o ut writte n n otificati o n t o t he s p o ns or. T he 
i n vesti gat or m ust e ns ure t hat t he rec or ds c o nti n ue t o be st ore d sec urely f or as l o n g as t he y are 
mai ntai ne d.
W he n partici pa nt data are t o be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h 
data are pr o m ptl y  a n d irre v oca bly delete d fr o m all s yste ms.
T he i n vesti gat or(s) 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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 5 9
1 0. 1. 6. 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 grit y of t he data collecte 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 C R F.
T he s p o ns or or desi g nee will perf or m m o nit ori n g t o c o nfir m t hat data e ntere d i nt o t he C R F 
b y  a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce d oc u me nts; 
t hat t he safety a n d ri g hts of partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y  is bei n g 
c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her st u d y  
a gree me nts, IC H G C P g ui deli nes, a n d all a p plica ble re g ulat or y  re q uire me nts.
1 0. 1. 7. Use of Me dic al Rec or ds
T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are re q ueste d b y 
Pfizer Safet y , w here et hicall y a n d scie ntificall y j ustifie d a n d per mitte d b y l ocal re g ulati o ns, 
t o e ns ure partici pa nt safet y.
D ue t o t he p ote ntial f or a partici pa nt t o be re -i de ntifie d fr o m t heir me dical rec or ds, t he 
f oll o wi n g acti o ns m ust be ta ke n w he n me dical rec or ds are se nt t o t he s p o 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/fax n u m ber, e mail a d dress) .
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 0

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 sys te m if a vaila ble). 
T here ma y  be u n pla n ne d sit uati o ns w here t he s p o ns or ma y re q uest me dical rec or ds (e g, 
s hari n g me dical rec or ds s o t hat t he s p o ns or ca n 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. 8. 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 n y 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/ C R O if re q ueste d t o d o s o b y  t he res p o nsi ble IR 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. The in vesti gat or s hall pr o m ptl y  i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f oll o w- u p.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a n y c o nflict 
bet wee n t he c o ntract a n d t his pr ot oc ol, t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts.
1 0. 1. 9. 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 joi nt p u blicati o n de vel o pe d b y t he 
in 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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 1
T he i n vesti gat or a grees t o refer t o t he pri mar y  p u blicati o n i n a n y s u bse q ue nt p u blicati o ns. 
Pfizer will n ot pr o vi de a n y fi na ncial c o m pe nsati o n f or t he i n vesti gat or’s partici pati o n i n t he 
pre parati o n of t he pri mar y c o n gress a bstract, p oster, prese nt ati 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 mpleti 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 ty pe of discl os ure of t he st u d y res ults (c ollecti vel y, “ pu 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 perty 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 y s 
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 n y pre vi o usl y u n discl ose d 
c o nfi de ntial i nf or mati o n bef ore discl os ure, e xce pt f or a n y st u d y-i nter ve nti o n or Pfizer-relate d 
i nf or mati o n necessar y f or t he a p pr o priate scie ntific prese ntati o n or u n dersta n di n g of t he 
st u d y res ults. F or j oi nt p u blicati o ns, sh o ul d t here be disa gree me nt re gar di n g i nter pret ati o n 
a n d/ or prese ntati o n of s pecific a nal ys is res ults, res ol uti o n of, a n d res p o nsi bilit y f or, s uc h 
disa gree me nts will be t he c ollecti ve res p o nsi bilit y  of all a ut h ors of t he p u blicati o n.
F or all p u blicati o ns relati n g t o t he st u d y, t he i n vesti gat or a n d Pfiz er 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 in vesti gat or will 
discl ose a n y relati o ns hi p wit h Pfizer a n d a n y rele va nt p ot e 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. A ll 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 blic ati o n.
1 0. 1. 1 0. 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 s u p p orti n g st u d y d oc u me ntati o n/st u d y  p ortal or ot her electr o nic 
s yste m. 
T o facilitate access t o t heir i n vesti gat or a n d t he s p o ns or’s M QI f or st u d y-relate d me dical 
q uesti o ns or pr o ble ms fr o m n o n-st u d y healt hcare pr ofessi o nals, 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, (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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 2
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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 3
1 0. 2. A p pe n di x 2: Cli nic al L a b or at or y Tests
T he f oll o wi n g safet y la b orat or y  tests will be perf or me d at ti mes defi ne d i n t he S o A secti o n of 
t his pr ot oc ol. A d diti o nal la b orat or y res ults ma y be re p orte d o n t hese sa m ples as a res ult of 
t he met h o d of a nalys is or t he t ype of a nal yz er use d b y t he cli nical la b orat or y, or as deri ve d 
fr o m calc ulate d val ues; f or e xa m ple: calc ulati o n of esti m ate d ki d ne y f u ncti o n (ie, 2 0 2 1 
C K D -E PI  e G F R). T hese a d diti o nal tests w o ul d n ot re q uire a d diti o nal c ollecti o n of bl o o d. 
U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u d y 
t o assess a ny percei ve d safet y iss ues.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 4
T a ble 4 .
Pr ot oc ol -Re q uire d L a b or at or y Assess me nts
H e m at ol o g y
C he mistr y
Uri n al ysis
Ot her
H e m o gl o bi n
H e m at ocrit
R B C c o u nt
Platelet c o u nt
W B C c o u nt
T otal ne utr o p hils ( A bs)
E osi n o p hils ( A bs)
M o n oc ytes ( A bs)
Bas o p hils ( A bs)
L y m p h oc ytes ( A bs)
Urea
Creati ni ne
C ystati n C a
e G F R, e Cr Cl b
Gl uc ose (fasti n g)
Calci u m
S o di u m
P otassi u m
C hl ori de
T otal C O 2 ( bicar b o nate)
A S T, A L T
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
F or s us pecte d 
DI CI/ DI KI: 
Creati ni ne ( Screat) 
C ystati n C a ( Sc ys) 
e G F R ( Screat o nl y a n d 
c o m bi ne d Screat + Sc ys)
e Cr Cl b
Uri ne al b u mi n-t o-
creati ni ne rati o ( U A C R)
L ocal d i pstic k:
p H
Gl uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nitrites
Le u k oc yte esterase
La b orat or y:
Micr osc o p y a n d 
cult ure c
Uri ne dr u g scree ni n g e, uri ne 
c oti ni ne, pre g na n c y test 
( β-h C G) f
At scree ni n g:

F S H d

He patitis B s urface 
a nti ge n

He patitis C a nti b o d y
a.
C ystati n C ( Sc ys): Scree ni n g or Baseli ne Sc ys is rec o m me n de d t o hel p differe ntiate p ost -baseli ne DI KI 
fr o m DI CI. P ost- baseli ne, Sc ys is meas ure d if a n d o nl y if ser u m creati ni ne i ncrease p ost -baseli ne is o bser ve d 
(see Secti o n 7. 1. 1 ).
b.
Scree ni n g a n d Baseli ne e G F R o r e Cr Cl is meas ure d wit h Screat-base d f or m ula. A ge -s pecific ki d ne y 
f u ncti o n calc ulati o n (see Secti o n 1 0. 6. 2 ) is rec o m me n de d t o assess prese nce or a bse nce of p ost- baseli ne 
c ha n ge i n ki d ne y f u ncti o n .
c.
O nl y if U TI is s us pecte d a n d uri ne di pstic k is p ositi ve f or nitrites or le u k oc yte esterase or b ot h .
d.
F or c o nfir mati o n of p ost me n o pa usal stat us o nl y i n fe males < 6 0 years ol d a n d n ot usi n g h or m o nal or 
H R T o nl y.
e.
T he mi ni m u m re q uire me nt f or dr u g scree ni n g i ncl u des c oca ine, T H C, o piates/ o pi oi ds, be nz o diaze pi nes, 
a n d a m p heta mi nes ( ot hers are site - a n d st u d y-s pecific).
f.
L ocal uri ne testi n g will be sta n dar d f or t he pr ot oc ol u nless ser u m testi n g is re q uire d b y l ocal r e g ulati o n 
or I R B/ E C. See S o A f or c ollecti o n ti mes.
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he C R F.
A n y  re mai ni n g ser u m/ plas ma fr o m sa m ples c ollecte d f or cli nical safety la b orat or y  
meas ure me nts at baseli ne a n d at all ti mes 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 o n of t he st u d y. U p o n c o m pleti o n of t he st u d y, t hese retai ne d safet y 
sa m ples ma y be use d f or t he assess me nt of e x pl orat or y safety bi o mar kers or u ne x pecte d 
safety fi n di n gs . T hese data will n ot 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 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 5
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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


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


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 7
E ve nts N O T Meeti n g t he A E Defi niti o n

A n y  cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal safety 
assess me nts t hat are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y  t he 
i n vesti gat or t o be m ore se vere t ha n e x pecte d f or t he partici pa nt’s c o n diti o n.

T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms 
of t he disease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he 
partici pa nt’s c o n diti o n.

Me dical or s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y): t he c o n diti o n t hat 
lea ds 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 os pit aliz ati o n
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n a d mitte d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or 
o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h y sicia n’s 
office or o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A E s. 
If a c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, t he 
e ve nt is seri o us. W he n i n d o u bt as t o w het her “ h os pitalizati o n” occ urre d or
was 
necessar y , t he A E s h o ul d be c o nsi dere d seri o us.
H os pitalizati o n f or electi ve treat me nt of a pree xisti n g c o n diti o n t hat di d n ot w orse n 
fr o m baseli ne is n ot c o nsi dere d a n A E.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 8
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 his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce, s uc h as u nc o m plicate d hea dac he, na usea, 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 mac o vi gila nce pers o n nel. S uc h cases are als o c o nsi dere d f or re p orti n g as 
pr o d uct defects, if a p pr o pri ate.
g.
Ot her sit u ati o ns:

Me dical or scie ntific j u d g me nt s h o ul d be e xercise d b y  t he i n vesti gat or i n deci di n g 
w het her S A E re p orti n g is a p pr o priate i n ot her sit uati o ns, s uc h as si g nifica nt 
me dical e ve nts t hat ma y je o par dize t he partici pa nt or ma y  re q uire me dical or 
s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve 
defi niti o n. T hese e ve nts s h o ul d us uall y  be c o nsi dere d seri o us.

E xa m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve 
treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d 
d y scrasias or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of 
dr u g de pe n de nc y  or dr u g a b use.
1 0. 3. 3. Rec or di n g / Re p orti n g a n d F oll o w - Up of A Es a n d/ or S A E s D uri n g t he Acti ve 
C ollecti o n Peri o d
A E a n d S A E Rec or di n g / Re p orti n g
T he ta ble bel o w s u m marizes t he re q uire me nts f or rec or di n g A Es o n t he C R F a n d f or 
re p orti n g S A Es usi n g t he C T S A E Re p ort F or m t o Pfizer Safet y t hr o u g h o ut t he acti ve 
c ollecti o n peri o d. T hese re q uire me nts are deli neate d f or 3 t ypes of e ve nts: ( 1) S A Es; ( 2) 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 6 9
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 dical 
ter mi n ol o g y a n d t he sa me A E ter m s h o ul d be use d o n b ot h t he C R F a n d t he C T S A E 
Re p ort F or m f or re p 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 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 i s 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.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 0

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.

It is n ot acce pta ble f or t he i n vesti gat or t o se n d p h ot oc o pies of t he partici pa nt’s 
me dical rec or ds t o Pfizer Safet y  i n lie u of c o m pleti o n of t he C T S A E Re p ort 
F or m A E or S A E C R F pa ge.

T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are 
re q ueste d by Pfizer Safet y . I n t his case, all partici pa nt i de ntifiers, wit h t he 
e xce pti o n of t he partici pa nt n u m ber, will be re dacte d o n t he c o pies of t he me dical 
rec or ds bef ore s u b missi o n t o Pfizer Safet y . Refer t o Secti o n 1 0. 1. 9 f or acti o ns 
t hat m ust be ta ke n w he n me dical rec or ds are se nt t o t he s p o ns or or s p o ns or 
desi g nee.

T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s ym pt o ms, a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n o sis 
( n ot t he i n di vi d ual si g ns/s ym pt o ms) will be d oc u me nte d as t he A E or S A E.
Assess me nt of I nte nsit y
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d 
d uri n g t he st u d y a n d assi g n it t o 1 of t he f oll o wi n g cate g ories: 

Mil d: A t y pe of A E t hat is us uall y  tra nsie nt a n d ma y re q uire o nl y mi ni mal 
treat me nt or t hera pe utic i nter ve nti o n. T he e ve nt d oes n ot ge nerall y i nterfere wit h 
us ual A D L .

M o derate: A t y pe of A E t hat is us uall y  alle viate d wit h a d diti o nal s pecific 
t hera pe utic inter 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 inte 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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 1

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 he i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y 
f or e ver y e ve nt bef ore t he i niti al tr a ns missi o n of t he S A E d at a t o t he 
s p o ns or.

T he i n vesti gat or ma y  c ha n ge t heir o pi ni o n of ca usalit y  i n li g ht of f oll o w-u p 
i nf or mati o n a n d se n d an S A E f oll o w -u p re p ort wit h t he u p date d ca usalit y  
assess me nt.

T he ca usalit y  assess me nt is o ne of t he criteria use d w he n deter mi ni n g re g ulat or y 
re p orti n g re q uire me nts.

If t he i n vesti gat or d oes n ot k n o w w het her or n ot t he st u d y i nter ve nti o n ca use d t he 
eve 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 
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 .
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 2

Ne w or u p date d i nf or mati o n wil l be rec or de d i n t he ori gi nall y s u b mitte d 
d oc u me nts .

T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 2 4 
h o urs of recei pt of t he i nf or mati o n.
1 0. 3. 4. Re p orti n g of S A E s
S A E Re p orti n g t o Pfizer S afet y vi a a n Electr o nic D C T

T he pri mar y  mec ha nis m f or re p orti n g a n S A E t o Pfizer Safet y will be t he 
electr o nic D C T (e g, e S A E or P S S A) .

If t he electr o nic sys te m is u na vaila ble, t he n t he site will use t he pa per S A E 
re p ort f or m (see ne xt secti o n) t o re p ort t he e ve nt wit hi n 2 4 h o urs.

T h e 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 .

Facsi mile tra ns missi o n of t he C T S A E Re p ort F or m is t he bac k-u p met h o d t o 
tra ns mit t his i nf or mati o n t o Pfizer Safet y i n case P S S A is u na vaila ble f or m ore 
t ha n 2 4 h o urs.

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, se c ure d ( Tra ns p ort La yer Sec urit y) or pass w or d-pr otecte d e mail. I f 
n o ne of t hese met h o ds ca n be use d, n otificati o n b y tele p h o ne is acce pta ble wit h a 
c o p y of t he C T S A E Re p ort F or m se nt by o ver ni g ht mail or c o urier ser vice.

I nitial n otificati o n via tele p h o ne d oes n ot re place t he nee d f or t he i n vesti gat or t o 
c o m plete a n d si g n t he C T S A E Re p ort F or m pa ges wit hi n t he desi g nate d 
re p orti n g ti me fra mes.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 3
1 0. 4. A p pe n di x 4: C o ntr ace pti ve a n d B arrier G ui d a nce
1 0. 4. 1. M ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
Male partici pa nts are eli gi ble t o partici pate if t he y  a gree t o t he f oll o wi n g re q uire me nts d uri n g 
t he i nter ve nti o n peri o d a n d f or at least 2 8 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 (a) is n ot pre g na nt or breastfee di n g; ( b) 
a grees t o n ot d o nate e g gs ( o va, o oc y tes) f or t he p ur p ose of re pr o d ucti o n at least 2 8 d a y s 
f oll o wi n g t he last d ose of st u d y i nter ve nti o n; a n d (c) at least 1 of t he f oll o wi n g c o n diti o ns 
a p plies:

Is n ot a W O C B P (see defi niti o n i n Secti o n 1 0. 4. 3 ).
O R

Is a W O C B P w h o a grees t o use a hi g hly effecti ve c o ntrace pti ve met h o d (fail ure rate 
of < 1 % per ye ar) wit h l o w user de pe n de nc y d uri n g t he i nter ve nti o n peri o d a n d f or at 
least 2 8 da y s after t he last d ose of st u d y i nter ve nti o n, w hic h c orres p o n ds t o t he ti me 
nee de d t o eli mi nate a n y re pr o d ucti ve safety ris k of t he st u d y i nter ve nti o n(s). T he 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


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


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 5
2.
P ost me n o pa usal fe male .

A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati ve me dical ca us e. 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 d iti o nal hi g hly effecti ve met h o d of c o ntrace pti o n 
s h o ul d be use d. T he s per mat o ge nesis c ycle is a p pr o xi matel y 9 0 da ys.
Hi g hl y Effecti ve Met h o ds T hat A re User D e pe n de nt 
6.
C o m bi ne d (estr o ge n - a n d pr o gest o ge n -c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ulati o n:

Oral + b arrier*

I ntra va gi nal + b arrier*
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 6

Tra ns der mal + b arrier*
7.
Pr o gest o ge n - o nly h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:

Oral + b arrier *

I njecta ble + b arrier *
8.
Se x ual A bsti ne nce
Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  if defi ne d as 
refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d 
wit h t he st u d y  i nter ve nti o n. T he relia bilit y of se x ual absti ne nce nee ds t o be e val uate d 
i n relati o n t o t he d urati o n of t he st u d y a n d t he preferre d a n d us ual lifestyl e of t he 
partici pa nt .
* Acce pta ble barrier met h o ds t o be use d c o nc o mita ntl y wit h o pti o ns 6 or 7 f or t he st u dy 
i ncl u de a ny of t he f oll o wi n g:

Male or
fe male c o n d o m wit h or wit h o ut s per mici de;

Cer vical ca p, dia p hra g m , or s p o n ge wit h s per mici de;

A c o m bi nati o n of male c o n d o m wit h eit her cer vical ca p, dia p hra g m , or s p o n ge 
wit h s per mici de ( d o u ble -barrier met h o ds).
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


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


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


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 7 9
1 0. 6. A p pe n di x 6 : Ki d ne y S afet y: M o nit ori n g G ui deli nes
1 0. 6. 1. L a b or at or y Assess me nt of C h a n ge i n Ki d ne y F u ncti o n a n d Detecti o n of Ki d ne y 
I nj ur y
Sta n dar d ki d ne y  safet y m o nit orin g re q uires assess me nt of baseli ne a n d p ost baseli ne Screat 
meas ure me nt t o esti mate ki d ne y f u ncti o n [ Screat -base d e G F R] or creati ni ne cleara nce 
[e Cr Cl]). O btai ni n g Scree ni n g or Baseli ne Sc ys a n d p ost baseli ne refle x Sc ys (if c o nfir me d 
Screat i ncrease ≥0. 3 m g / d L) ma kes it feasi ble t o disti n g uis h A KI fr o m DICI . If Screat 
i ncrease is c o nfir me d after baseli ne, t he n refle x meas ure me nt of Sc ys is i n dicate d:
A D U L T S: C urre ntl y, 2 0 2 1 C K D -E PI  e G F R e q uati o ns ( Screat o nl y-base d a n d c o m bi ne d 
Screat pl us Sc y s- base d) are vali d f or use i n a d ults o nl y. At baseli ne Screat a n d Sc ys val ues 
are nee de d t o calc 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. 6 . 2. 1.) a n d by c o m bi ne d Screat pl us Sc ys -base d e q uati o n. W he n p ost -baseli ne 
Screat i ncrease ≥0. 3 m g/ d L  is co nfir me d, t he n refle x Sc y s meas ure me nt is nee de d t o e na ble 
p ost -baseli ne c o m paris o n of e G F R c ha n ges ( Screat o nl y - base d e G F R a n d c o m bi ne d Screat 
pl us Sc y s e G F R). 
1 0. 6. 2. A ge -S pecific Ki d ne y F u ncti o n C alc ul ati o n Rec o m me n d ati o ns
1 0. 6. 2. 1. A d ults ( 1 8 Y e ars a n d A b o ve) — 2 0 2 1 C K D- E P I E q u ati o ns
e G F R ( m L/ mi n/ 1. 7 3 m²) [7 ]
2 0 2 1 C K D -
E PI            
Scre at O nl y
Scre 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 × ( Screat/ 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 × ( Screat/ 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 × ( Screat/ 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 × ( Screat/ 0. 9) -1. 2 0 0  ×  ( 0. 9 9 3 8) A ge
2 0 2 1 C K D -
E PI           
Scre at -Sc ys 
C o m bi ne d
Scre 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 × ( Screat/ 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 × ( Screat/ 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 × ( Screat/ 0. 7) -0. 5 4 4  × ( Sc ys/ 0. 8) -0. 3 2 3  × ( 0. 9 9 6 1) A ge
Fe male
if > 0. 7
if > 0. 8
e G F R = 1 3 0 × ( Screat/ 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 × ( Screat/ 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 × ( Screat/ 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 × ( Screat/ 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 × ( Screat/ 0. 9)-0. 5 4 4  ×  ( Sc ys/ 0. 8) - 0. 7 7 8  × ( 0. 9 9 6 1) A ge
1 0. 6. 3. Ki d ne y F u ncti o n C alc ul ati o n T o ols
T he s p o ns or has pr o vi de d t he f oll o wi n g res o urces t o i n vesti gati o nal sites w he n re q uire d t o 
calc ulate a ge -s pecific ki d ne y f u ncti o n at Scree ni n g, Baseli ne, a n d p ost-Ba seli 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. 6. 2 ) a n d ca n use rec o m me n de d o nli ne ki d ne y f u ncti o n calc ulat ors 
t o re d uce t he li keli h o o d of a calc ulati o n err or. 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 0
T he U nite d States Nati o nal Ki d ne y  F o u n dati o n O nli ne Calc ulat ors. 

A d ults ( 1 8 y ears a n d a b o ve) - 2 0 2 1 C K D -E PI  Creati ni ne O nli ne Calc ulat or (e G F R): 
htt ps:// w w w. ki d ne y . or g/ pr ofessi o nals/ K D O QI/ gfr _calc ulat or
I n vesti gati o nal sites are res p o nsi ble t o e ns ure t hat t he acc urate a ge-s pecific e q uati o n is 
selecte d a n d t hat t he c orrect u nits f or ser u m creati ni ne ( m g/ d L o nl y), ser u m c ystati n C ( m g/ L 
o nl y ), t otal b o 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 
a n d c o nfir m c orrect ness of t he ki d ne y  f u ncti o n calc ulati o n res ults a n d (ii) e val uate t he 
calc ulate d val ue wit hi n t he c o nte xt of hist orical i nf or mati o n a vaila ble t o t he m i n t he 
partici pa nt’s me dical rec or d. I n vesti gat ors are res p o nsi ble f or t he cli nical o versi g ht of t he 
partici pa nt eli gi bilit y  pr ocess, ki d ne y f u ncti o n calc ulati o n, a n d d ose selecti o n a n d 
a dj ust me nts per st u d y pr ot oc ol. In vesti gat ors are e nc o ura ge d t o direct q uesti o ns or 
u ncertai nties re gar di n g ki d ne y f u ncti o n a n d d osi n g t o t he Pfizer Cli nical Tea m a n d Me dical 
M o nit or, if nee de d.
1 0. 6. 4. A d verse E ve nt Gr a di n g f or Ki d ne y S afet y L a b or at or y A b n or m alities
A E gra di n g f or decli ne i n ki d ne y  f u ncti o n (ie, e G F R or e Cr Cl) will be acc or di n g t o Ki d ne y 
Disease: I m pr o vi n g Gl o bal O utc o mes ( K DI G O) criteria f or a d ult partici pa nts.
K DI G O criteri a 
gr a de ( G)
St u d y 
P o p ul ati o n
G 1  
G 2  
G 3  
G 4  
G 5
Decre ase d Ki d ne y 
F u nct i o n d ue t o 
eit her Ac ute or 
C hr o nic Ki d ne y 
I nj ur y 
A d ult 
partici pa nts
e G F R 
( mL/ mi n/ 1. 7 3 m²)
≥9 0 
≥6 0 t o 8 9
3 0 t o 5 9 
1 5 t o 2 9
< 1 5
K DI G O al b u mi n uri a ( A) 
criteri a
A 1
A 2
A 3
Al b u mi n -t o-cre ati ni ne 
r ati o ( A C R)
< 3 0 m g/ g
O R     
< 3 m g/ m m ol 
3 0 t o 3 0 0 m g/ g
O R 
3 t o 3 0 m g/ m m ol
> 3 0 0 m g/ g 
O R 
> 3 0 m g/ m m ol
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


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


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


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 3
1 0. 8. A p pe n di x 8 : Pr o hi bite d C o nc o mit a nt Me dic ati o ns T h at M a y Res ult i n D DI  
T he pr o hi bite d c o nc o mita nt me dicati o ns liste d bel o w a n d a nti bi otics s h o ul d n ot be ta ke n wit h 
sis u nat o vir f or t he peri o d of ti me at least e q ual t o 5 half -li ves pl us 1 4 da ys prece di n g t he first 
d ose of st u d y  i nter ve nti o n, a n d t hr o u g h o ut t he c o n d uct of t he st u d y.
T he Pfizer st u d y tea m is t o be n otifie d of a n y  pr o hi bite d me dicati o ns ta ke n d uri n g t he st u d y. 
After c o ns ulti n g wit h t he s p o ns or, t he i n vesti gat or will ma ke a j u d g me nt o n t he o n g oi n g 
partici pati o n of a n y partici pa nt wit h pr o hi bite d me 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 t he s p o ns or t o i ncl u de or e xcl u de 
s pecific dr u gs or dr u g cate g ories f or vari o us reas o ns (e g, e mer gi n g D DI res ults f or t he I M P, 
a vaila bilit y of ne w i nf or mati o n i n literat ure o n t he D DI p ote ntial of ot her dr u gs) if t he o verall 
be nefit:ris k assess me nt is n ot i m pacte d or if t he c ha n ges d o n ot si g nifica ntl y i m pact t he 
safety of partici pa 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 . Si nce 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 C Y P 2 B 6, se nsiti ve narr o w TI s u bstrates of C Y P 2 B 6 are 
e xcl u de d.
Sis u nat o vir als o ma y  be a n i n hi bit or of O C T 1 a n d M A T E 1 tra ns p orters; t heref ore, se nsiti ve 
s u bstrates of t hese tra ns p orters are e xcl u de d.
Alt h o u g h n ot all -i ncl usi ve, a list of me dicati o ns t hat are pr o hi bite d i n t his st u d y is pr o vi de d 
bel o w. Site staff s h o ul d c o ns ult wit h t he s p o ns or or desi g nee wit h a n y q uesti o ns re gar di n g 
p ote ntial D DI.
I n vesti gat ors s h o ul d c o ns ult t he pr o d uct la bel f or a n y ot her me dicati o n use d d uri n g t he st u d y 
f or i nf or mati o n re gar di n g me dicati o n t hat is pro hi bite d f or c o nc o mita nt use. 
Pr o hi bite d C o nc o mit a nt Me dic ati o ns
C Y P 3 A I n hi bit ors
C Y P 3 A I n d ucers
M o der ate
Str o n g
M o der ate
Str o n g
A pre pita nt
B oce pre vir
B ose nta n
A pal uta mi de
Ci pr ofl o xaci n
C o bicistat
Efa vire nz
Car ba maze pi ne
C o ni va pta n
Da n o pre vir
Etra viri ne
E nzal uta mi de
Criz oti ni b
Dasa b u vir
P he n o bar bital
Mit ota ne
C y cl os p ori ne
El vite gra vir
Pri mi d o ne
P he n 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
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 4
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
Alfe nta nil
L o vastati n
Alfe nta nil
At or vastati n
L urasi d o ne
Aste miz ole
A va nafil
Mara vir oc
Cisa pri de
B u des o ni de
Mi daz ola m
C y cl os p ori ne
B us pir o ne
Nal o xe g ol
Di h y dr oer g ota mi ne
Darife naci n
Nis ol di pi ne
Er g ota mi ne
Dar u na vir
Q uetia pi ne
Fe nta n yl
Dasati ni b
Sil de nafil
Pi m ozi de
Dr o ne dar o ne
Si m vastati n
Q ui ni di ne
E basti ne
Sir oli m us
Sir oli m us
Eletri pta n
Tacr oli m us
Tacr oli m us
E plere n o ne
Tica grel or
Terfe na di ne
E ver oli m us
T ol va pta n
I br uti ni b
Ti pra na vir
I n di na vir
Triaz ola m
Fel o di pi ne
Var de nafil
L o mita pi de
Fe nta n yl
Se nsiti ve M A T E 1 S u bstr ates
Metf or mi n
Se nsiti ve C Y P 2 B 6 S u bstr ates
C Y P 2 B 6 S u bstr ates 
wit h N arr o w T her a pe utic I n de x
Vel patas vir
C y cl o p h os p ha mi 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 b itas 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
E l 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
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 5
Ket oc o naz ole
V o n o praza n a n d 
a mo xicilli n a n d 
clarit hr o m yci n
L o nafar ni b
V o xila pre vir
Se nsiti ve O C T S u bstr ates
I mati ni b 
N ot a n all -i ncl usi ve list.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 6
1 0. 9. A p pe n di x 9 : Or al S ol uti o n or S us pe nsi o n P al at a bilit y Q uesti o n n aire
1.
Q uesti o n naire s h o ul d be a d mi nistere d t o a d ult partici pa nts , prefera bly b y a n urse.
2.
Use c ol ore d c o p y of t he Palata bilit y  Q uesti o n naire.
3.
D o n ot alter (re d uce or e nl ar ge) t he ori gi n al size of t he P al at a bilit y Q uesti o n n aire .
4.
Please c ollect t he f oll o wi n g bac k gr o u n d i nf or mati o n:
B ac k gr o u n d I nf or m ati o n
St u d y  #/ St u d y Site
Peri o d a n d Da y
Partici pa nt I D ( Ra n d I D)
Treat me nt
C ollect Date
C ollecte d B y
E ntere d i n PI M S B y
C hec ke d i n PI M S B y
Q uesti o n naire F ull y  C o m plete d (circle o ne)
Yes/ N o
Ple ase a ns wer t he f oll o wi n g q uesti o ns a n d pr o vi de a m ar k ( X) o n t he c ol or b ar at 
a p pr o xi m atel y 1 (i m me di atel y), 5, 1 0 a n d 2 0 mi n utes after d osin g . Ple ase e ns ure 
p artici p a nt h as access t o t hese descri pti o ns w he n c o m pleti n g t he q uesti o n n aire. 
Q 1: M o ut h feel – Please tell us a b o ut t he m o ut h feel (s uc h as gritti ness, stic ki ness, wa xi ness) 
of t he pr o d uct y o u taste d. G o o d re prese nts n or mal m o ut h feel. Ba d re prese nts ba d m o ut h 
feel. 
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 7
Q 2: Bitter ness – Please tell us a b o ut t he de gree of bitter ness of t he pr o d uct y o u taste d. G o o d 
re prese nts n ot bitter at all. Ba d re prese nts e xtre mel y bitter. 
Q 3: S weet ness – Please tell us a b o ut t he de gree of s weet taste of t he pr o d uct y o u taste d.
G o o d re prese nts s weet. Ba d re prese nts n ot s weet at all. 
Q 4: S o ur ness – Please tell us a b o ut t he de gree of s o ur taste of t he pr o d uct y o u taste d. G o o d 
re prese nts n ot s o ur at all. Ba d re prese nts e xtre mel y  s o ur. 
Q 5: Salti ness – Please tell us a b o ut t he de gree of salt y  taste of t he pr o d uct y o u taste d. G o o d 
re prese nts n ot salt y  at all. Ba d re prese nts e xtre mel y salt y. 
Q 6: T o n g ue/ m o ut h b ur n – Please te ll us a b o ut t he de gree of t o n g ue/ m o ut h b ur n of t he 
pr o d uct y o u taste d. G o o d re prese nts n o b ur n at all. Ba d re prese nts e xtre me b ur n. 
Q 7: O verall li ki n g – Please i n dicate h o w m uc h y o u li ke or disli ke t he pr o d uct y o u taste d.
G o o d re prese nts li ke. Ba d re prese nts disli ke. 
Det ails t o assess q uesti o n n aire descri be d bel o w: 
After t he partici pa nts places t he mar k ( X) o n t he c ol or bar, t he mai n Cli nical C o or di nat or of 
t he st u d y a n d his bac k u p or desi g nee will pr occe d f oll o ws:
①
Meas uri n g t he t otal le n gt h of t he bar o n t he pri nte d q uesti o n naire:
-
Place t he 3 0 c m st u d y de dicate d tra ns pare nt r uler verticall y at t he t o p of t he c ol or bar 
( 0 le vel o ver t he gree n t o p bar) a n d meas ure t he le n gt h till t he e n d of t he re d b ott o m 
bar
②
Meas uri n g
t he place me nt of t he “ X” of t he c ol or bar of t he pri nte d q uesti o n naire:
-
Place t he st u d y de dicate d tra ns pare nt r uler at t he t o p of t he c ol or bar a n d meas ure t he 
le n gt h till t he i ntersecti o n p oi nt le vel of t he “ X” mar ke d o n t he c ol or bar
③
E nteri n g data i n PI M S
-
E nter t he t he le n gt h of t he w h ole bar (i n m m) a n d meas ure d dista nce t o t he p oi nt le vel 
of “ X” (i n m m) i n PI M S acc or di n g t o eac h taste assess me nt u n der g o ne b y  eac h 
partici pa nt .
-
Data will be E ntere d b y / C hec ke d b y  tw o differe nt Cli nical C o or di nat ors ( Main & Bac k 
u p) or desi g nee.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 8
E x a m ple: H o w t o pr o vi de a m ar k ( X ) o n t he c ol or b ar.

G o o d (sc ore = 0)
B a d (sc ore = 1 0 0)
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 8 9
Wit hi n 1 mi n ute (i m me di atel y) after d osi n g
C ollecti o n ti me:  _ _ _ _ _ _ _ _
Pr o vi de a m ar k ( X ) o n t he c ol or b ar .
M o ut h 
Feel
Bitter ness
S weet ness
S o ur ness
S alti ness
T o n g ue/
M o ut h 
B ur n
O ver all 
Li ki n g
B a d
G o o d
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 0
5 mi n utes after d osi n g
C ollecti o n ti me:  _ _ _ _ _ _ _ _
Pr o vi de a m ar k ( X ) o n t he c ol or b ar .
M o ut h 
Feel
Bitter ness
S weet ness
S o ur ness
S alti ness
T o n g ue/
M o ut h 
B ur n
O ver all 
Li ki n g
B a d
G o o d
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 1
1 0 mi n utes after d osi n g
C ollecti o n ti me:  _ _ _ _ _ _ _ _
Pr o vi de a m ar k ( X ) o n t he c ol or b ar.
M o ut h 
Feel
Bitter ness
S weet ness
S o ur ness
S alti ness
T o n g ue/
M o ut h 
B ur n
O ver all 
Li ki n g
B a d
G o o d
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 2
2 0 mi n utes after d osi n g
C ollecti o n ti me:  _ _ _ _ _ _ _ _
Pr o vi de a m ar k ( X ) o n t he c ol or b ar.
M o ut h 
Feel
Bitter ness
S weet ness
S o ur ness
S alti ness
T o n g ue/
M o ut h 
B ur n
O ver all 
Li ki n g
B a d
G o o d
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 3
A d diti o n al Fee d b ac k – After c o m pleti n g t he “ 2 0 mi n ute after d osi n g” palata bilit y  q uesti o ns, 
please pr o vi de a n y a d diti o nal descri pti ve fee d bac k i n t he b o x bel o w re gar di n g t he taste or 
o d or of t he dr u g.
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 4
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
% C V
perce nt c oefficie nt of variati o n
A 1 t o A 3
al b u mi n uria ( K DI G O al b u mi n uria se verit y sta n dar dizati o n)
A bs
a bs ol ute
A C R
al b u mi n-t o-creati ni ne rati o
A D L
acti vit y/acti vities of daily li vi n g
A E
a d verse e ve nt
A KI
ac ute ki d ne y i nj ur y
A L P
al kali ne p h os p hatase
A L T
ala ni ne a mi n otra nsferase
A PI
acti ve p har mace utical i n gre die nt
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c ur ve
A U C 1 2
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 1 2 h o urs
A U C 2 4
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 2 4 h o urs
A U C ta u
area u n der t he c o nce ntrati o n -ti me c ur ve at stea dy state o ver t he 
d osi n g i nter val ta u
A V
atri o ve ntric ular
A x M P
au xiliar y  me dici nal pr o d uct
B B S
Bi os peci me n Ba n ki n g S yste m
Bili
bilir u bi n
BI D
t wice-dail y d osi n g
-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
C F R
C o de of Fe deral Re g ulati o ns
CI
c o nfi de nce i nter val
CI O M S
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces
C K
creati ne ki nase
C K D -E PI
c hr o nic ki d ne y disease e pi de mi ol o g y
C L
t otal cleara nce of dr u g fr o m e g, plas ma
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 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
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 5
A b bre vi ati o n
Ter m
C T C A E
C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts
C TI S
Cli nical Trial I nf or mati o n S y ste m
C V
car di 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
D DI
dr u g -dr u g i nteracti o n 
DI C
dr u g i n ca ps ule
DI CI
dr u g -i n d uce d creati ni ne i ncrease
DI KI
dr u g -i n d uce d ki d ne y i nj ur y
DI LI
dr u g -i n d uce d li ver i nj ur y
D P B
dr y  p o w der ble n d
E C
et hics c o m mittee
E C C
e mer ge nc y c o ntact car d
E C G
electr ocar di o gra m or electr ocar di o gra p h y
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 D R
e xte m p ora ne o us dis pe nsi n g rec or d
e G F R
esti mate d gl o mer ular filtrati o n rate
E M A
E ur o pea n Me dici nes A ge nc y
e S A E
electr o nic seri o us a d verse e ve nt
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n U ni o n Dr u g Re g ulati n g A ut h orities Cli nical Trials 
( E ur o pea n Cli nical Trials Data base)
F S H
f ollicle-sti m ulati n g h or m o ne
F/ U
f oll o w-u p
G C P
G o o d Cli nical Practice
G G T
ga m ma -gl uta m y l tra nsferase
GI
gastr oi ntesti nal
H B P c y cl o de xtri n
h y dr o x y p r o pyl -β -c ycl o de xtri n
H Bs A g 
he patitis B s urface a nti ge n
H C V A b
he patitis C a nti b o d y
HI V
h u ma n i m m u n o deficie nc y vir us
H R
heart rate
H R T
h or m o ne re place me nt t hera p y
I B
I n vesti gat or’s Br oc h ure
I C D
i nf or me d c o nse nt d oc u me nt
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts 
f or P har mace uticals f or H u ma n Use
I C U
i nte nsi ve care u nit
I D
i de ntificati o n
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 6
A b bre vi ati o n
Ter m
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
K DI G O
Ki d ne y  Disease I m pr o vi n g Gl o bal O utc o mes
L B B B
left b u n dle bra nc h bl oc k
L F T
li ver f u ncti o n test
L R TI
l o wer res pirat or y tract i nfecti o n
M A D
m ulti ple asce n di n g d ose
M A T E
m ulti dr u g a n d t o xi n e xtr usi o n
M QI
me dicall y  q ualifie d i n di vi d ual
M T D
ma xi m u m t olerate d d ose
N A
n ot a p plica ble
NI M P
n o ni n vesti gati o nal me dici nal pr o d uct
N O A E L
n o o bser ve d a d verse effect le vel
O A T
or ga nic a ni o n tra ns p orti n g
O A T P
or ga nic a ni o n tra ns p orti n g p ol y pe pti de
O C T
or ga nic cati o n tra ns p orter
P C R U
Pfizer Cli nical Researc h U nit
P E
p h y sical e xa m
P -g p
p -gl yc o pr otei n
PI M S
P hase 1 Ma na ge me nt S yste m
P K
p har mac o ki netic(s)
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 Tc
c orrecte d Q T i nter val
Q Tc F
Q Tc c orrecte d usi n g Fri dericia’s f or m ula
q ual
q ualitati ve
R B C
re d bl o o d cell
R O A
r o ute of a d mi nistrati o n
R S V
res pirat or y sy n c ytial vir us
S A D
si n gle asce n di n g d ose
S A E
seri o us a d verse e ve nt
S A P
Statistical A nal y sis Pla n
Screat
ser u m creati ni ne 
Sc y s
ser u m c ystati n C
S D
sta n dar d de viati o n
S o A
sc he d ule of acti vities
S O C
s yste m or ga n class
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
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 7
A b bre vi ati o n
Ter m
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 E A E
treat me nt e mer ge nt a d verse e ve nt
T H C
tetra hy dr oca n na bi n ol
TI
t hera pe utic i n de x
T ma x
ti me t o reac h Cma x
U L N
u p per li mit of n or mal
U A C R
uri ne al b u mi n-t o-creati ni ne rati o
U S
U nite d States
U S P
U nite d States P har mac o p oeia
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
0 9 0 1 7 7 e 1 9 d 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)


P F -0 7 9 2 3 5 6 8
Pr ot oc ol C 5 2 4 1 0 1 4
Fi nal Pr ot oc ol, 1 9 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 ( 1 4 A pril 2 0 2 3)
Pa ge 9 8
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. L a 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 ytial Vir us -Ass ociate d 
H os pitalizati o ns A m o n g Y o u n g C hil dre n: 2 0 1 5 -2 0 1 6. Pe di atrics. 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 I nfect 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 Vir al L u n g I nfecti o ns. S heffiel d 
( U K) 2 0 1 6.
6.
Ki m L , R ha B, A bra ms o n J S, et al. I de ntif yi 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 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 8 1 2 b 9 1\ A p pr o v e d\ A p pr o v e d O n: 2 3- M a y- 2 0 2 3 1 3: 2 1 ( G M T)

SAP_001.pdf: 
Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 of 1 5
Pr ot oc ol C 5 2 4 1 0 1 4
A R A N D O MI Z E D, P H A S E 1, SI N G L E -B LI N D, M U L TI -P E RI O D S T U D Y T O 
I N V E S TI G A T E T H E P A L A T A BI LI T Y O F P F-0 7 9 2 3 5 6 8 O R A L S U S P E N SI O N I N 
DI F F E R E N T LI Q UI D V E HI C L E S 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 atistic al A n al ysis Pl a n 
( S A P)
Versi o n :
1
D ate:
1 5 A u g 2 0 2 3
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 2 of 1 5
T A B L E O F C O N T E N T S
LI S T O F T A B L E S .....................................................................................................................3
LI S T O F FI G U R E S ...................................................................................................................3
A P P E N DI C E S ...........................................................................................................................3
1. V E R SI O N HI S T O R Y ............................................................................................................4
2. I N T R O D U C TI O N .................................................................................................................4
2. 1. M o dificati o ns t o t he A nal y sis Pla n Descri be d i n t he Pr ot oc ol..................................4
2. 2. St u d y  O bjecti ves, E n d p oi nts, a n d Esti ma n ds............................................................4
2. 3. St u d y  Desi g n.............................................................................................................4
3. E N D P OI N T S A N D B A S E LI N E V A RI A B L E S:  D E FI N I TI O N S A N D 
C O N V E N TI O N S ..................................................................................................................6
3. 1. Pri mar y  E n d p oi nt(s)..................................................................................................6
3. 1. 1. Palata bilit y  Assess me nt Q uesti o n naire Sc ori n g Metrics:  m o ut h feel, 
bitter ness, s weet ness, s o ur ness, salti ness, t o n g ue/ m o ut h b ur n, o verall 
li ki n g..................................................................................................................6
3. 2. Sec o n dar y  E n d p oi nt(s)..............................................................................................6
3. 3. Ot her E n d p oi nt(s) ......................................................................................................6
3. 4. Baseli ne Varia bles .....................................................................................................6
3. 5. Safet y E n d p oi nts .......................................................................................................6
3. 5. 1. A d verse E ve nts .............................................................................................7
3. 5. 2. C li nical La b orat or y Assess me nts .................................................................7
3. 5. 3. Vital Si g ns ....................................................................................................7
3. 5. 4. Electr ocar di o gra ms....................................................................................... 7
4. A N A L Y SI S S E T S ( P O P U L A T I O N S F O R A N A L Y SI S)..................................................... 7
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S ......................................................8
5. 1. H y p ot heses a n d Decisi o n R ules ................................................................................8
5. 2. Ge neral Met h o ds .......................................................................................................8
5. 2. 1. A nal y ses f or C o nti n u o us E n d p oi nts .............................................................9
5. 2. 2. A nal y ses f or Bi nar y/ Cate g orical E n d p oi nts .................................................9
5. 3. Met h o ds t o Ma na ge Missi n g Data ............................................................................9
6. A N A L Y S E S A N D S U M M A RI E S ........................................................................................9
6. 1. Pri mar y  E n d p oi nt(s)..................................................................................................9
6. 1. 1. Se nsiti vit y / S u p ple me ntar y A nalys is.............................................................9
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 3 of 1 5
6. 2. Sec o n dar y  E n d p oi nt(s)..............................................................................................9
6. 3. S u bset A nal y ses.......................................................................................................1 0
6. 4. Baseli ne a n d Ot her S u m maries a n d A nal ys es .........................................................1 0
6. 4. 1. De m o gra p hic S u m maries ............................................................................1 0
6. 4. 2. St u d y  C o n d uct a n d Partici pa nt Dis p ositi o n................................................1 0
6. 4. 3. St u d y  Treat me nt E x p os ure .........................................................................1 0
6. 4. 4. C o nc o mita nt Me dicati o ns a n d N o n dr u g Treat me nts.................................. 1 0
6. 5. Safet y S u m maries a n d A nal yses .............................................................................1 0
6. 5. 1. A d verse E ve nts ...........................................................................................1 0
6. 5. 2. Cli ncal L a b orat or y Assess me nts .................................................................1 0
6. 5. 3. Vital Si g ns ..................................................................................................1 0
6. 5. 4. Electr ocar di o gra ms..................................................................................... 1 1
7. I N T E RI M A N A L Y S E S .......................................................................................................1 1
8. R E F E R E N C E S ....................................................................................................................1 1
A P P E N DI C E S .........................................................................................................................1 2
LI S T O F T A B L E S
Ta ble 1.
S u m mar y  of C ha n ges..................................................................................4
LI S T O F FI G U R E S
Fi g ure 1.
Sa m ple D osi n g Sc he me ..............................................................................5
A P P E N DI C E S
A p pe n di x 1. L ist of A b bre viati o ns...........................................................................................1 2
A p pe n di x 2. Oral S ol uti o n or S us pe nsi o n Palata bilit y  Q uesti o n naire.....................................1 2
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 4 of 1 5
N O T E: It alicize d te xt wit hi n t his d oc u me nt has bee n ta ke n ver bati m fr o m t he pr ot oc ol.
1. V E R SI O N HI S T O R Y
T a ble 1 .
S u m m ar y of C h a n ges
Versi o n /
D ate
Ass oci ate d 
Pr ot oc ol 
A m e n d me nt
R ati o n ale
S pecific C h a n ges
1
1 5 A u g 2 0 2 3
Ori gi nal
1 9 Ma y  2 0 2 3
N/ A
N/ A
2. I N T R O D U C TI O N
T he p ur p ose of t his st u dy is t o perf or m p al at a bility assess me nts t o ai d i n t he devel o p me nt of 
pe di atric f or m ul ati o ns of sis u n at ovir ( P F- 0 7 9 2 3 5 6 8).
T his statistical a nal ysis pla n (S A P ) pr o vi des t he detaile d met h od ol o g y  f or s u m mar y a n d 
statistical a nal yses of t he data c ollecte d i n St u d y C 5 2 4 1 0 1 4. T his d oc u me nt ma y  m o dif y t he 
pla ns o utli ne d i n t he pr ot oc ol; 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 n or its a nal y ses will als o be reflecte d i n a pr ot oc ol a me n d me nt .  
2. 1. M o dific ati o ns
t o t he A n al ysis Pl a n Descri be d i n t he Pr ot oc ol
N/ A
2. 2. St u d y O bjecti ves , E n d p oi nts, a n d Esti m a n ds
T here are n o esti ma n ds f or t his st u d y .
T y pe
O bjecti ve
E n d p oi nt
Pri m ar y :
Ot her

T o assess t he p al at a bility 
attri b utes of sis u n at ovir i n 
differe nt f or m ul ati o ns

P al at a bility Assess me nt 
Q uesti o n n aire Sc ori n g Metrics:  
m o ut h feel, bitter ness, s weet ness, 
s o ur ness, s alti ness, 
t o n g ue/ m o ut h b ur n, over all 
liki n g
Sec o n d ar y:
Safet y

T o assess s afety a n d t oler a bility 
f oll o wi n g or al a d mi nistr ati o n of 
e ac h sis u n at ovir f or m ul ati o ns

Assess me nt of T E A Es, cli nic al 
l a b or at ory a b n or m alities a n d 
vit al si g ns 
2. 3. St u d y Desi g n
T his is a si n gle -bli n d, r a n d o mize d, m ulti -peri o d st u dy i n he alt hy m ale a n d/ or fe m ale a d ult 
p artici p a nts . A p pr oxi m ately 1 2 p artici p a nts will assess t he p al at a bility attri b utes of a t ot al of 
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 5 of 1 5
6 f or m ul ati o ns ( F or m ul ati o ns A t o F) over 2 d ays i n a cr oss over m a n ner. T here will be a 
m axi m u m of 4 peri o ds e ac h d ay, a n d o ne f or m ul ati o n will be a d mi nistere d at e ac h peri o d f or 
t asti n g i n a bli n di n g f as hi o n , exce pt o n D ay 2 w here t here will be o ne peri o d wit h n o 
a d mi nistr ati o n. A mi ni m u m of 3 p artici p a nts fr o m e ac h ge n der is re q uire d.
All p artici p a nts will be disc h ar ge d o n D ay 2 after c o m pleti o n of all re q uire d assess me nts. If 
t he p artici p a nt acci de nt ally i n gests t he t aste s a m ple c o nt ai ni n g t he active i n gre die nt, he/s he 
will n ot be per mitte d t o c o nti n ue ev al u ati n g a ny f urt her t aste s a m ples a n d will be wit h dr a w n 
fr o m t he st u dy.
P artici p a nts w h o disc o nti n ue fr o m t he st u dy m ay be re pl a ce d at t he s p o ns or’s discreti o n. T he 
re pl ace me nt p artici p a nt will receive t he s a me tre at me nt se q ue nces as t he p artici p a nt w h o 
disc o nti n ue d.
T he st u d y  sa m ple d osi n g sc he me is s h o w n bel o w i n Fi g ure 1 .
Fi g ure 1.
S a m ple D osi n g Sc he me
Sessi o n 1 ( D a y 1)
Sessi o n 2 ( D a y 2)
Peri o d 1
Peri o d 2
Peri o d 3
Peri o d 4
Peri o d 5
Peri o d 6
Peri o d 7
Peri o d 8
N = 3
A 
B  
D 
C  
A 
E
N o
F
N = 3
B 
C  
A  
D 
E 
F  
A
N o
N = 3
C  
D 
B  
A 
F
N o
E  
A
N = 3
D  
A 
C 
B
N o
A 
F 
E
Tre at me nt A:  
 m g/ m L Sis u n at ovir
Tre at me nt B:  
 m g/ m L Sis u n at ovir,
 
Tre at me nt C:
Tre at me nt D: 
 m g/ m L Sis u n at ovir a n d
Tre at me nt E:  
 m g/ m L Sis u n at ovir a n d
Tre at me nt F:  
 m g/ m L Sis u n at ovir,
 
N o: N o a d mi nistr ati o n a n d i n dic ate d as ‘ X’ i n r a n d o miz ati o n
N ote
 
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( 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


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 6 of 1 5
3. E N D P OI N T S A N D B A S E LI N E V A RI A B L E S: D E FI NI TI O N S A N D 
C O N V E N TI O N S
3. 1. Pri m ar y E n d p oi nt(s)
3. 1. 1. P al at a bilit y Assess me nt Q uesti o n n aire Sc ori n g Metrics:  m o ut h feel, bitter ness, 
s weet ness, s o ur ness, s alti ness, t o n g ue/ m o ut h b ur n, o ver all li ki n g
P artici p a nts will s wirl t he s a m ple i n t he m o ut h f or a p pr oxi m ately 1 0 sec o n ds, a n d t he n s p it it 
o ut. P artici p a nts will assess v ari o us as pects of t he t aste, i ncl u di n g m o ut h feel, bitter ness, 
s weet ness, s o ur ness, s altiess, t o n g ue/ m o ut h b ur n, a n d over all liki ng usi n g t he Or al S ol uti o n 
or S us pe nsi o n P al at a bility Q uesti o n n air (A p pe n di x 2 ).
Palatia blit y  assess me nts will be carrie d at a p pr o xi matel y 1 mi n ute, 5 mi n utes, 1 0 mi n utes, 
a n d 2 0 mi n utes after d osi n g.
T he d at a c ollecte d f or p al at a bility assess me nt usi n g t he s p o ns or -pr ovi de d p al at a bility 
q uesti o n n aire will be n u meri c ally derive d by me as uri n g le n gt h ( usi n g a sc ale wit h gr a d ati o ns 
of at le ast 0. 1 c m) of t he ‘x’ m arke d by t he p artici p a nt rel ative t o t he ‘ g o o d tr ait’. F or 
p al at a bility assess me nt, t he d at a us e d i n t he a n alysis will be tr a nscri be d a n d resc ale d t o a 
sc ore fr o m 0 t o 1 0 0 fr o m t he r a w me as ure me nts o n t he q uesti o n n aire. 
3. 2. Sec o n d ar y E n d p oi nt(s)
As liste d i n Secti o n 2. 2 , t he sec o n dar y e n d p oi nt is relate d t o t he safety/ t olera bilit y of oral 
a d mi nistrati o n of sis u nat o vir a n d is descri be d i n Secti o n 3. 5 .
3. 3. Ot her E n d p oi nt (s)
N/ A
3. 4. B aseli ne V ari a bles
N/ A
3. 5. S afet y E n d p oi nts
T he f oll o wi n g data will be c o nsi dere d i n sta n dar d safet y s u m maries (see pr ot oc ol f or 
c ollecti o n ti mes, baseli ne assess me nt, a n d list of para meters):

A d verse e ve nts ( A E)

Cli nical la b orat or y  assess me nts

Vital si g ns

Electr ocar di o gra ms
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 7 of 1 5
3. 5. 1. A d verse E ve nts
A n y  a d verse e ve nts occ urri n g f oll o wi n g start of treat me nt will be c o nsi dere d as treat me nt-
e mer ge nt a d verse e ve nts ( T E A E). If a n A E st arts o n t he sa me da y as t he first d ose date, it 
will be c o nsi dere d treat me nt- e mer ge nt u ness t he C R F data i n dicates ot her wise via e x plicitl y  
rec or di n g ti me f or A E o mset w hic h has occ urre d bef ore t he first treat me nt d osi n g. E ve nts 
t hat occ ur d uri n g f oll o w- u p wit hi n t he la g ti me of u p t o 2 8-3 5 da y s after t he last d ose of 
st u d y i nter ve nti o n will be c ou nte d as treat me nt -e mer ge nt a n d attri b ute d t o t he last treat me nt 
ta ke n. E ve nts t hat occ ur d uri n g t he was h o ut peri o d bet wee n treat me nts will be c o u nte d as 
treat me nt-e mer ge nt a n d attri b ute d t o t he pre vi o us treat me nt ta ke n. T he ti me peri o d f or 
c ollecti n g 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. T he al g orit h m will n ot c o nsi der a n y e ve nts t hat 
starte d pri or t o t he first d ose date.
A 3 -tier a p pr oac h f or s u m marizi n g a d verse e ve nts ( A Es) will n ot be use d d ue t o t he l o w 
n u m ber of partici pa nts pla n ne d t o be recr uite d.
3. 5. 2. Cli nic al L a b or at or y Assess me nts
Cli nical la b orat or y  assess me nts will be perf or me d as descri be d i n t he pr ot oc ol.
T o deter mi ne if t here are a n y cli nicall y si g nifica nt la b orat or y a b n or malities, t he 
hae mat ol o gical , cli nical c he mistr y (ser u m) a n d uri nal ysis safet y tests will be assesse d a gai nst 
t he criteria s pecifie d i n t he s p o ns or re p orti n g sta n dar ds. T he assess me nt will n ot ta ke i nt o 
acc o u nt w het her eac h partici pa nts’s baseli ne test res ult , t he meas ure me nt o n Da y - 1, is wit hi n 
or o utsi de t he la b orat or y  refere nce ra n ge f or t he partic ular la b orat or y para meter.
3. 5. 3. Vit al Si g ns
Bl o o d press ure a n d p ulse rate will be meas ure d as descri be d i n t he pr ot oc ol. T he b aseli ne
meas ure me nt is t he pre d ose meas ure me nt o n Da y 1. C ha n ges fr o m baseli ne will be defi ne d 
as t he c ha n ge bet wee n t he p ost d ose meas ure me nt o n Da y  2 a n d t he baseli ne meas ure me nt.
3. 5. 4. Electr oc ar di o gr a ms
Si n gle 1 2 -lea d E C Gs will be perf or me d as descri be d i n t he pr ot oc ol. T he H R, P R , Q T, Q Tc F, 
a n d Q R S i nter vals will be ca pt u re d.
T he baseli ne meas ure me nt is t he pre d ose meas ure me nt o n Da y  1. C ha n ges fr o m baseli ne will 
be defi ne d as t he c ha n ge bet wee n t he p ost d ose meas ure me nt o n Da y  2 a n d t he baseli ne 
meas ure me nt . C ha n ge fr o m baseli ne i n Q T i nter val, heart rate, Q Tc F i nter val, P R i nter val, 
a n d Q R S c o m ple x will be deter mi ne d.
4. A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S )
D ata f or all partici pa nts will be assesse d t o deter mi ne if partici pa nts meet t he criteria f or 
i ncl usi o n i n eac h a nalys is p o p ulati o n pri or t o u n bli n di n g a n d releasi n g t he data base a n d 
classificati o ns will be d oc u me nte d per sta n dar d o perati n g pr oce d ures.
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 8 of 1 5
P o p ul ati o n
Descri pti o n
A p plic a ble A n al ysis
E nr olle d
“ E nr olle d ” me a ns a p a rtici p a nt’s 
a gree me nt t o p artici p ate i n a cli nic al 
st u dy 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 
r a n d o miz ati o n t o st u dy i nterve nti o n. 
A p artici p a 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 dr a w n pri or t o p artici p ati n g i n 
a ny st u dy activity after scree ni n g. 
P ote nti al p artici p a nts w h o are 
scree ne d f or t he p ur p ose of 
deter mi ni n g eli gi bility f or t he st u dy, 
b ut d o n ot p artici p ate i n t he st u dy, 
are n ot c o nsi dere d e nr olle d, u nless 
ot her wise s pecifie d by t he pr ot oc ol.
Ev al u a ble 
a n alysis set
All p artici p a nts w h o t ake at le ast 1 
d ose of st u dy i nterve nti o n a n d pr ovi de 
at le ast 1 c orres p o n di n g assess me nt 
t o t he P al at a bility Q uesti o n n aire.
Pri mar y  E n d p oi nt
S afety 
a n alysis set
All p artici p a nts r a n d o mly assi g ne d t o 
st u dy i nterve nti o n a n d w h o t ake at 
le ast 1 d ose of st u dy i nterve nti o n. 
P artici p a nts will be a n alyze d 
acc or di n g t o t he pr o d uct t hey act u ally 
receive d.
Sec o n dar y  E n d p oi nt
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S
5. 1. H y p ot heses a n d Decisi o n R ules
N o statistical h y p ot hesis will be teste d i n t his st u d y .
5. 2. Ge ner al Met h o ds
Descri pti ve a nal ys es will be perf or me d, a n d s o me meas ures will be s u m marize d usi n g 
gra p hical re prese ntati o ns
T he a nal ys es relate d t o t he pri mar y a n d sec o n dar y e n d p oi nts will be base d o n t he a p pr o priate 
p o p ulati o n f or a nal ys is (see Secti o n 4 ).
U nless ot her wise sta te d, all s u m maries a n d pl ots will be prese nte d b y treat me nt gr o u p. T he 
f oll o wi n g treat me nt gr o u p la bels ( or si milar) will be use d:
-
Treat me nt A:  
 m g/ m L Sis u nat o vir 
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)
C CI
C CI


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 9 of 1 5
-
Treat me nt B: 
 m g/ m L Sis u nat o vir,
 
-
Treat me nt C:
-
Treat me nt D:  
 m g/ m L Sis u nat o vir a n d
-
Treat me nt E:  
 m g/ m L Sis u nat o vir a n d
-
Treat me nt F:  
m g/ m L Sis u nat o vir, 
 
5. 2. 1. A n al yses f or C o nti n u o us E n d p oi nts
F or c o nti n u o us varia bles; t he data will be s u m marize d usi n g n u m ber of partici pa nts , 
arit h metic mea n, sta n dar d de viati o n ( S D), me dia n a n d ra n ge ( mi ni m u m a n d ma xi m u m) i n 
acc or da nce wit h t he s p o ns or re p ort i n g sta n dar ds.
5. 2. 2. A n al yses f or Bi n ar y/ C ate g oric al E n d p oi nts
F or bi nar y  or cate g orical varia bles ; n u m ber of partici pa nts, n u m bers a n d perce nta ges of 
partici pa nts meeti n g t he cate gr orical criteria will be prese nte d i n acc or da nce wit h t he s p o ns or 
re p orti n g sta n dar ds.
5. 3.
Met h o ds t o M a n a ge Missi n g D at a
F or t he a nal ys is of safet y e n d p oi nts, t he s p o ns or data sta n dar d r ules f or i m p utati o n will be 
a p plie d.
6. A N A L Y S E S A N D S U M M A RI E S .
6. 1. Pri m ar y E n d p oi nt (s)
T he se ns or y attri b utes ( m o ut h feel, bitter ness, s weet ness, s o ur ness, salti ness, t o n g ue/ m o ut h 
b ur n, o verall li ki n g) fr o m t he palata bilit y q uesti o n naires ( A p pe n di x 2 ) will be liste d a n d 
descri pti vel y s u m marize d b y sessi o n, ti me p oi n t, a n d treat me nt, if a p pr o priate. S u m mar y  
statistics ( mea n a n d 9 0 % CI) will be calc ulate d f or t he vari o us q uesti o ns. Ra dar pl ots f or 
eac h of 4 ti me p oi nts, s u m marizi n g all attri b utes will be ge nerate d. B o x pl ots of eac h attri b ute 
will be pl otte d a gai nst t he ti me p oi nts. A n y  a d diti o nal fee d bac k data as c ollecte d b y t he 
palata bilit y  q uesti o n naire will be liste d.
6. 1. 1. Se nsiti vit y/ S u p ple me nt ar y A n al ysis
If t he data per mits, palata bilit y of sis u nat o vir ma y be a nalyz e d usi n g a mi xe d effects m o del.
Data fr o m m ulti ple time p o nts will be c o m bi ne d t o be treate d as t he res p o nse. Treat me nt, 
se q ue nce, ti me p oi nt, a n d peri o d will be fi xe d effects; a n d partici pa nt wit hi n se q ue nce will be 
a ra n d o m effect. Esti mates a n d c orres p o n di n g 9 0 % CI s will be o btai ne d fr o m t he m o del.
6. 2. Sec o n d a r y E n d p oi nt(s)
T he sec o n dar y  e n d p oi nts are relate d t o safety/ t olera bilit y a n d t heir a nalys es are descri be d i n 
Secti o n 6. 5 .
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 0 of 1 5
6. 3. S u bset A n al yses
T here are n o pla n ne d s u bset a nal ys es.
6. 4. B aseli ne a n d Ot her S u m m aries a n d A n al yses
6. 4. 1. De m o gr a p hic S u m m aries
De m o gra p hic c haracteristics will be s u m marize d f or e nr olle d p o p ulati o n i n acc or da nce wit h 
t he s p o ns or re p orti n g sta n dar ds.
6. 4. 2. St u d y C o n d uct a n d P artici p a nt Dis p ositi o n
Partici pa nts e val uati o n gr o u ps will s h o w e n d of st u d y  partici pa nt disp ositi o n. Fre q ue nc y  
c o u nts will be s u p plie d f or partici pa nt disc o nti n uati o n(s) b y o verall a n d treat me nt. Data will 
be re p orte d i n acc or da nce wit h t he s p o ns or re p orti n g sta n dar ds.
6. 4. 3. St u d y Tre at me nt E x p os ure
St u d y  treat me nt e x p os ure will be liste d.
6. 4. 4. C o nc o mit a nt Me dic ati o ns a n d N o n dr u g T re at me nts
All c o nc o mita nt me dicati o n(s) as well as n o n -dr u g treat me nt(s) will be re p orte d i n t he 
listi n gs acc or di n g t o c urre nt s p o ns or re p orti n g sta n dar ds.
6. 5. S afet y S u m m aries a n d A n al yses
All safet y a nal ys es will be perf or me d o n t he Safet y  an al y sis set.
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.
6. 5. 1. A d verse E ve nts
A d verse e ve nts will be re p orte d i n acc or da nce wit h t he s p o ns or re p orti n g sta n dar ds.
Partici pa nt disc o nti n uati o ns d ue t o a d verse e ve nts will be detaile d b y  treat me nt, w here 
a p pr o priate. Data will be re p orte d i n acc or da nce wit h t he s p o ns or re p orti n g sta n dar ds.
6. 5. 2. Cli nc al L a b or at or y Assess me nts
La b orat or y  data will be s u m marize d b y n o mi nal ti me p oi nt i n accor da nce wit h t he s p o ns or 
re p orti n g sta n dar ds. C ha n ges fr o m baseli ne will be re p orte d. Baseli ne is as defi ne d i n Secti o n 
3. 5. 2 .
6. 5. 3. Vit al Si g ns
Vital si g ns data will be s u m marize d b y n o mi nal ti me p oi nt i n acc orda nce wit h t he s p o ns or 
re p orti n g sta n dar ds. C ha n ges fr o m baseli ne will be re p orte d. Baseli ne is as defi ne d as i n 
Secti o n 3. 5. 3 .
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 1 of 1 5
6. 5. 4. Electr oc ar di o gr a m s
E C G data will be s u m marize d b y  n o mi nal ti me p oi nt i n acc or da nce wit h t he s p o nsor r e p orti n g 
sta n dar ds. Baseli ne is as defi ne d i n Secti o n 3. 5. 4 . C ha n ges fr o m baseli ne f or t he E C G 
para meters H R, Q Tc F , P R i nter val, a n d Q R S c o m ple x will s u m marize d usi n g s p o ns or 
re p orti n g sta n dar ds. T hese c orres p o n d t o t he Pfizer G ui da nce 1 i n Secti o n 8 .
T he fre q ue nc y  of u nc orrecte d Q T val ues a b o ve 5 0 0 ms will be ta b ulate 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 fr o m baseline i n t he f oll o wi n g cate g ories i n Ta ble 2 will be ta b ulate d .
T a ble 2.
C ate g oric al Cl asses f or E C Gs of P ote nti al Cli nic al C o ncer n
De gree of Pr ol o n g ati o n
Mil d ( ms)
M o der ate ( ms)
Se vere ( ms)
A bs ol ute val ue of Q Tc F
> 4 5 0 - 4 8 0
> 4 8 0 - 5 0 0
> 5 0 0
I ncrease fr o m baseli ne i n Q Tc F
> 3 0 a n d ≤6 0
> 6 0
A bs ol ute val ues a n d c ha n ges fr o m baseli ne i n Q T, heart rate, Q Tc F, P R a n d Q R S will be 
liste d usi n g s p o ns or re p orti n g sta n dar ds.
Listi n gs of partici pa nts wit h a n y si n gle p ost -d ose Q Tc F val ue > 5 0 0 msec will als o be 
pr o d uce d.
7. I N T E RI M A N A L Y S E S
N o i nteri m a n alysis will be c o n d ucte d f or t his st u dy.
8. R E F E R E N C E S
1.
Pfizer G ui da nce f or E val uati o n of Q T / Q Tc I nter val Pr ol o n gati o n a n d Pr oarr h yt h mic
P ote ntial f or N o n -a ntiarr h yt h mic Dr u gs; Me m bers of t he Car di o vasc ular Safet y &
A d vis or y  C o u ncil ( C V S A C); Ja n uar y 2 6, 2 0 1 8
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 2 of 1 5
A P P E N DI C E S
A p pe n di x 1. List o f A b bre vi ati o ns
A b bre vi ati o n
Ter m
A E
a d verse e ve nt
CI
c o nfi de nce i nter val
E C G
electr ocar di o gra m
H R
heart rate
m g
milli gra m
m L
millilitre
N/ A
n ot a p plica ble
Q Tc
c orrecte d Q T
Q Tc F
c orrecte d Q T ( Fri dericia met h o d)
S A P
statistical a nal ysis pla n
S D
sta n dar d de viati o n
S O P
sta n dar d o perati n g pr oce d ure
T E A E
treat me nt-e mer ge nt a d verse e ve nt
A p pe n di x 2. Or al S ol uti o n or S us pe nsi o n P al at a bilit y Q uesti o n n aire
1.
Q uesti o n naire s h o ul d be a d mi nistere d t o a d ult partici pa nts , prefera bly b y a n urse.
2.
Use c ol ore d c o p y of t he Palata bilit y  Q uesti o n naire.
3.
D o n ot alter (re d uce or e nl ar ge) t he ori gi n al size of t he P al at a bilit y Q uesti o n n aire .
4.
Please c ollect t he f oll o wi n g bac k gr o u n d i nf or mati o n:
B ac k gr o u n d I nf or m ati o n
St u d y  #/ St u d y Site
Peri o d a n d Da y
Partici pa nt I D ( Ra n d I D)
Treat me nt
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 3 of 1 5
C ollect Date
C ollecte d B y
E ntere d i n PI M S B y
C hec ke d i n PI M S B y
Q uesti o n naire F ull y  C o m plete d (circle o ne)
Yes/ N o
Ple ase a ns wer t he f oll o wi n g q uesti o ns a n d pr o vi de a m ar k ( X) o n t he c ol or b ar at 
a p pr o xi m atel y 1 (i m me di atel y), 5, 1 0 a n d 2 0 mi n utes after d osin g . Ple ase e ns ure 
p artici p a nt h as access t o t hese descri pti o ns w he n c o m pleti n g t he q uesti o n n aire. 
Q 1: M o ut h feel – Please tell us a b o ut t he m o ut h feel (s uc h as gritti ness, stic ki ness, wa xi ness) 
of t he pr o d uct y o u taste d. G o o d re prese nts n or mal m o ut h feel. Ba d re prese nts ba d m o ut h 
feel. 
Q 2: Bitter ness – Please tell us a b o ut t he de gree of bitter ness of t he pr o d uct y o u taste d. G o o d 
re prese nts n ot bitter at all. Ba d re prese nts e xtre mel y bitter. 
Q 3: S weet ness – Please tell us a b o ut t he de gree of s weet taste of t he pr o d uct y o u taste d. 
G o o d re prese nts s weet. Ba d re prese nts n ot s weet at all. 
Q 4: S o ur ness – Please tell us a b o ut t he de gree of s o ur taste of t he pr o d uct y o u taste d. G o o d 
re prese nts n ot s o ur at all. Ba d re prese nts e xtre mel y s o ur. 
Q 5: Salti ness – Please tell us a b o ut t he de gree of salt y  taste of t he pr o d uct y o u taste d. G o o d 
re prese nts n ot salt y at all. Ba d re prese nts e xtre mel y salt y. 
Q 6: T o n g ue/ m o ut h b ur n – Please tell us a b o ut t he de gree of t o n g ue/ m o ut h b ur n of t he 
pr o d uct y o u taste d. G o o d re prese nts n o b ur n at all. Ba d re prese nts e xtre me b ur n. 
Q 7: O verall li ki n g – Please i n dicate h o w m uc h y o u li ke or disli ke t he pr o d uct yo u taste d. 
G o o d re prese nts li ke. Ba d re prese nts disli ke. 
Det ails t o assess q uesti o n n aire descri be d bel o w: 
After t he partici pa nts places t he mar k ( X) o n t he c ol or bar, t he mai n Cli nical C o or di nat or of 
t he st u d y a n d his bac k u p or desi g nee will pr occe d f oll o ws:
①
Meas uri n g t he t otal le n gt h of t he bar o n t he pri nte d q uesti o n naire:
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 4 of 1 5
-
Place t he 3 0 c m st u d y de dicate d tra ns pare nt r uler verticall y at t he t o p of t he c ol or bar 
( 0 le vel o ver t he gree n t o p bar) a n d meas ure t he le n gt h till t he e n d of t he re d b ott o m 
bar
  ②
Meas uri n g t he place me nt of t he “ X” of t he c ol or bar of t he pri nte d q uesti o n naire:
-
Place t he st u d y de dicate d tra ns pare nt r uler at t he t o p of t he c ol or bar a n d meas ure t he 
le n gt h till t he i ntersecti o n p oi nt le vel of t he “ X” mar ke d o n t he c ol or bar
③
E nteri n g data i n PI M S
-
E nter t he t he le n gt h of t he w h ole bar (i n m m) a n d meas ure d dista nce t o t he p oi nt le vel 
of “ X” (i n m m) i n PI M S acc or di n g t o eac h taste assess me nt u n der g o ne b y  eac h 
partici pa nt.
-
Data will be E ntere d b y / C hec ke d b y  tw o differ e nt Cli nical C o or di nat ors ( Mai n & Bac k 
u p) or desi g nee.
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)


Pr ot oc ol C 5 2 4 1 0 1 4 (P F -0 7 9 2 3 5 6 8 / Sis u nat o vir ) Statistical A nal ysis Pla n
D M B 0 2 -G S O P -R F 0 2 7. 0 St atistic al A n alysis Pl a n Te m pl ate 3 1 -Ja n-2 0 2 2
P FI Z E R C O N FI D E N TI A L
T M F D oc I D: 9 8. 0 3
Pa ge 1 5 of 1 5
E x a m ple: H o w t o pr o vi de a m ar k ( X ) o n t he c ol or b ar.

G o o d (sc ore = 0)
B a d (sc ore = 1 0 0)
0 9 0 1 7 7 e 1 9 e 5 0 5 b 4 4\ A p pr o v e d\ A p pr o v e d O n: 2 8- S e p- 2 0 2 3 1 0: 0 1 ( G M T)